Conditioning Agents for Hair and Skin edited by Randy Schueller Perry Romanowski Alberto-Culver Company Melrose Park, IllinoisMARCEL MARCEL DEKKER, INC. N E W YORK • BASEL

ISBN: 0-8247-1921-2This book is printed on acid-free paper.HeadquartersMarcel Dekker, Inc.270 Madison Avenue, New York, NY 10016tel: 212-696-9000; fax: 212-685-4540Eastern Hemisphere DistributionMarcel Dekker AGHutgasse 4, Postfach 812, CH-4001 Basel, Switzerlandtel: 44-61-261-8482; fax: 44-61-261-8896World Wide Webhttp://www.dekker.comThe publisher offers discounts on this book when ordered in bulk quantities. For more infor-mation, write to Special Sales/Professional Marketing at the headquarters address above.Copyright© 1999 by Marcel Dekker, Inc. All Rights Reserved.Neither this book nor any part may be reproduced or transmitted in any form or by anymeans, electronic or mechanical, including photocopying, microfilming, and recording, orby any information storage and retrieval system, without permission in writing from thepublisher.Current printing (last digit);10 9 8 7 6 5 4 3 2 1PRINTED IN THE UNITED STATES OF AMERICA

About the SeriesThe Cosmetic Science and Technology series was conceived to permit discus-sion of a broad range of current knowledge and theories of cosmetic scienceand technology. The series is made up of books written either by a singleauthor or by a number of contributors to an edited volume. Authorities fromindustry, academia, and the government have participated in writing thesebooks. The aim of this series is to cover the many facets of cosmetic science andtechnology. Topics are drawn from a wide spectrum of disciplines ranging fromchemistry, physics, biochemistry, and analytical and consumer evaluations tosafety, efficacy, toxicity, and regulatory questions. Organic, inorganic, physi-cal, and polymer chemistry, emulsion technology, microbiology, dermatology,toxicology, and related fields all play a role in cosmetic science. There is little commonality in the scientific methods, processes, or for-mulations required for the wide variety of cosmetic and toiletries manufac-tured. Products range from hair care, oral care, and skin care preparations tolipsticks, nail polishes and extenders, deodorants, body powders, and aerosolsto such products as antiperspirants, dandruff and acne treatments, antimicro-bial soaps, and sunscreens. Cosmetics and toiletries represent a highly diversified field with manysubsections of science and \"art.\" Indeed, even in these days of high technology,\"art\" and intuition continue to play an important part in the development offormulations, their evaluation, and the selection of raw materials. There is a III

Iv About the Seriesmove toward more sophisticated scientific methodologies in the fields of claimsubstantiation, safety testing, product evaluation, and chemical analyses anda better understanding of the properties of skin and hair. Emphasis in this series is placed on reporting the current status of cos-metic technology and science in addition to historical reviews. The series hasgrown, dealing with the constantly changing technologies and trends in thecosmetic industry, including globalization. Several of the books have beentranslated into Japanese and Chinese. Contributions range from highly sophis-ticated and scientific treatises, to primers, descriptions of practical applica-tions, and pragmatic presentations. Authors are encouraged to present theirown concepts as well as established theories. Contributors have been askednot to shy away from fields that are still in a state of transition, or to hesitateto present detailed discussions of their own work. Altogether, we intend todevelop in this series a collection of critical surveys and ideas covering diversephases of the cosmetic industry. Conditioning Agents of Hair and Skin is the twenty-first book publishedin the Cosmetic Science and Technology series. The book includes detaileddiscussions of the biology of skin, the largest component of the human body,and hair. Not only are skin and hair responsible for our appearance, but theyalso provide important protective properties. Two other key areas covered inthe book are the chemicals used as conditioners in hair and skin care productsand the methods and new techniques for determining the efficacy of theseproducts and their ability to deliver conditioning to skin and hair. In additionto providing \"cosmetic\" effects, the conditioning agents must be functional,provide hair treatment, and make positive contributions to the health of theskin. I want to thank all the contributors for taking part in this project andparticularly the editors. Randy Schueller and Perry Romanowski, for develop-ing the concept of this book and contributing a chapter. Special recognition isalso due to Sandra Beberman and the editorial staff at Marcel Dekker, Inc. Inaddition, I would like to thank my wife, Eva, without whose constant supportand editorial help I would never have undertaken this project. Eric Jungermann, Ph.D.

PrefaceBiological surfaces, such as hair and skin, are vulnerable to damage from avariety of external sources. Such damage can make hair rough and unmanage-able and look dull, while skin can become dry, scaly, and itchy. Cosmetic prod-ucts are used to counteract this damage and to make skin and hair look andfeel better; in other words, the products put these surfaces in better condition.Hair conditioning products are primarily intended to make wet hair easier todetangle and comb and make dry hair smoother, shinier, and more manage-able. Skin conditioning products are primarily intended to moisturize whileproviding protection from the drying effects of sun, wind, and harsh deter-gents. The functional raw materials responsible for the conditioning ability ofthese products are the focus of this book. Conditioning Agents for Hair and Skin was prepared by cosmetic formu-lators, for cosmetic formulators. Our objective is to provide information thatis useful to anyone involved in formulating personal care products, from thenovice chemist to the seasoned veteran. For the beginning chemist, we aim toprovide a solid foundation of technical knowledge. For the seasoned formu-lator, we detail the latest state-of-the-art ingredients and testing proceduresused in their evaluation. The book is structured to give a complete review of the subject. Thefirst chapter serves as a general introduction. We define conditioning andprovide an overview of the types of materials and formulations used to achievethese effects. In addition, we discuss how to evaluate the performance of

Vi Prefaceconditioning products. Chapters 2 and 3 review the biological and physico-chemical aspects of hair and skin in order to provide an understanding of whatconditioning agents should accomplish. The next several chapters comprise the bulk of the text; they deal withthe individual conditioning agents used in hair and skin care products. Thematerials we have included were chosen because of their different conditioningeffects on biological surfaces. This section begins with a review of petrolatum,an occlusive material that provides conditioning by sealing moisture in skin.Next is a chapter about humectants, materials that attract and bind water toskin and hair. Conditioning agents that impart emolliency are described nextin a chapter about esters and oils. The rest of the chapters in this section dealwith ingredients that have an electrostatic affinity for biological surfaces. Theseinclude proteins and classic quaternized ammonium compounds as well aspseudo-cationic surfactants, like amine oxides. A discussion of cationic poly-mers is included as well. Two chapters in this section discuss novel silicone-derived materials and how they function in formulations. After discussing chemi-cal raw materials we felt it important to place this information in perspectiveby including a review of factors to consider when formulating these materialsinto finished products. Finally, we end the book by examining the testingmethods currently available for evaluation of conditioning formulations. We believe this approach will give the beginner an excellent overview ofthe subject while providing the veteran chemist with new insights into rawmaterials, formulations, and testing. As in many works of this type, there issome overlap of material between chapters and, while this may seem redun-dant, it is important to recognize the multifunctionality of many conditioningagents. As with any work of this nature, the state of the art is constantly chang-ing and we welcome comments from readers to be considered for incorpora-tion into future editions. Randy Schueller Perry Romanowski

ContentsAbout the Series HiPreface vContributors ix 1 1 Introduction to Conditioning Agents for Hair and Skin Randy Schueller and Perry Romanowski 13 2 Biology of the Hair and Skin 35 Zoe Diana Draelos 57 3 The Role of Biological Lipids in Skin Conditioning Peter M. Elias 95 4 Petrolatum: Conditioning Through Occlusion 111 David S. Morrison 5 Humectants in Personal Care Formulation: A Practical Guide Bruce W. Gesslein 6 Emollient Esters and Oils John Carson and Kevin F. Gallagher vii

viil Contents7 Proteins for Conditioning Hair and Skin 139 Gary A. Neudahl8 Organo-Modified Siloxane Polymers for Conditioning 167 Skin and Hair Eric S. Abrutyn9 Specialty Silicone Conditioning Agents 201 Anthony J. O'Lenick, Jr.10 Cationic Surfactants and Quaternary Derivatives for Hair and Skin Care 223Matthew F. Jurcyzk, David T. Floyd, and Burghard H. Gruning11 Polymers as Conditioning Agents for Hair and Skin 251 Bernard Idson12 Formulating Conditioning Products for Hair and Skin 281 Mort Westman13 Evaluating Effects of Conditioning Formulations on Hair 301 Janusz Jachowicz14 Evaluating Performance Benefits of Conditioning 337 Formulations on Human Skin Ronald L. Rizer, Monya L. Sigler, and David L. MillerIndex 369

ContributorsEric S. Abrutyn Senior Product Development Leader, The Andrew JergensCompany, Cincinnati, OhioJohn Carson Technical Director, Croda, Inc., Edison, New JerseyZee Diana Draelos Clinical Associate Professor, Department of Dermatol-ogy, Wake Forest University School of Medicine, Winston-Salen, and Derma-tology Consulting Services, High Point, North CarolinaPeter M. Elias Professor of Dermatology, University of California, SanFrancisco, and Veterans Affairs Medical Center, San Francisco, CaliforniaDavid T. Floyd Technical Director, Goldschmidt Chemical Corporation,Hopewell, VirginiaKevin F. Gallagher Croda, Inc., Edison, New JerseyBruce W. Gesslein Technical Manager, Specialty Chemicals Division, Aji-nomoto U.S.A., Inc., Teaneck, New JerseyBurghard H. Griining Senior Research Manager, Goldschmidt ChemicalCorporation, Hopewell, Virginia Ix

X ContributorsBernard Idson Professor, College of Pharmacy, University of Texas at Austin,Austin, TexasJanusz Jachowicz Science Fellow, International Specialty Products, Wayne,New JerseyMatthew F. Jurczyk Marketing Manager, Goldschmidt Chemical Corpora-tion, Hopewell, VirginiaDavid L. Miller President, CuDerm/Bionet, Inc., Dallas, TexasDavid S. Morrison Senior Research Associate, Penreco, The Woodlands,TexasGary A. Neudahl Technical Services Manager, Costec, Inc., Palatine, IllinoisAnthony J. O'Lenick, Jr. President, Lambent Technologies, Norcross,GeorgiaRonald L. Rizer Chief Investigator and Vice President of Operations, ThomasJ. Stephens & Associates, Inc., Carrollton, TexasPerry Romanowski Senior Research Chemist, Research and Development,Alberto-Culver Company, Melrose Park, IllinoisRandy Schueller Group Leader, Research and Development, Alberto-Cul-ver Company, Melrose Park, IllinoisMonya L. Sigler Senior Investigator, Thomas J. Stephens & Associates, Inc.,Carrollton, TexasMort Westman President, Westman Associates, Inc., Oak Brook, Illinois

1Introduction to Conditioning Agentsfor Hair and SkinRandy Schuetler and Perry RomanowskiAlberto-Culver Company, Melrose Park, IllinoisI. WHAT IS \"CONDITIONING\"?A. Definition of ConditioningThe purpose of this book is to educate the reader about the materials used tocondition hair and skin. To best accomplish this, the book is divided into threesections: Part One reviews the biological reasons hair and skin need to beconditioned, Part Two discusses the chemical conditioning agents that areavailable to the formulator, and Part Three provides strategies for formulatingand evaluating products containing these agents. Before beginning the discus-sion, we must first define what we mean when we talk about conditioning. Wesuggest that the reader view conditioning not as a single element or property,but as the combined effect of many influencing factors. Conditioning can meanmany things depending on the circumstances, and therefore any functionaldefinition of the term must be flexible enough to encompass muhiple mean-ings. For the purposes of this book we offer the following definition: A product can be said to have conditioning properties if it improves the quality of the surface to which it is applied, particularly if this improvement involves the cor- rection or prevention of some aspects of surface damage.With this definition as a framework with which to work, we can turn the dis-cussion to specific elements to consider when attempting to condition hair andskin. 1

2 Schueller and RomanowskiB. Components of ConditioningJust as conditioning is not a single entity, the condition of hair and skin cannotbe described by a single variable. Instead, the condition of the surface of hairand skin is determined by a series of properties, which can be considered tobe the components of conditioning. Viewed as a whole, these componentsdetermine the overall condition of hair and skin. We have attempted to groupthese components into categories, but this is difficult because the categoriesoverlap and interact to a large degree. For example, when discussing hair con-ditioning properties, one may say that softness is one beneficial conditioningcharacteristic and that shine is another. But don't both of these propertiesreally depend on the smoothness of the surface of the hair? Therefore, shouldone assume that surface smoothness is the ultimate aspect of conditioning, thecosmetic equivalent of quantum physics' quark? No, because surface analysisreveals only one aspect of the hair's condition and cannot fully explain othercontributing factors, such as moisture content, electrical conductivity, andlipid composition. To obtain a complete assessment of the hair's condition,these other factors must be taken into consideration. In our definition of con-ditioning, improvement to the substrate (hair or skin) is measured by evaluat-ing several physical, chemical, and perceptual factors. These factors can besorted into the following categories. Structural factors (how hair and skin are constructed) Compositional elements (what physiochemical components hair and skin contain) Visual appearance (how hair and skin look to the observer) Tactile perception (how hair and skin feel to the observer) Physical properties (how hair and skin behave)These factors will be discussed separately as they relate to hair and skin.1. Structural Factors a. Hair. Clearly, the structure of hair is an important consideration whenassessing its condition. Not surprisingly, Robbins (1, p. 212) notes that hair isdamaged by the breakdown or removal of structural elements. The specificcharacteristics of these elements are the focus of Chapter 2 and will not bediscussed in detail here. In this introductory chapter we will simply note thathair consists of protein that is organized into the cuticle (the outer layer ofoverlapping scales) and the cortex (the inner region consisting of bundledprotein fibers). It is the cuticle that is of primary interest when discussingconditioning products. We know from examining electron micrographs thatwhen the cuticular scales are raised, chipped, or broken, the hair's surface isperceptibly rougher. Even relatively simple actions, such as combing, can causelifting of these scales, which in turn leaves the cuticle even more vulnerable to

Introduction 3subsequent damage. With continued physical abrasion these cuticular defectscan become cracks or fissures which penetrate into the cortex. Sufficient deg-radation of the cortex will ultimately lead to breakage and loss of the hair shaft.Therefore, maintaining a smooth cuticular surface is essential to the conditionof hair. b. Skin. Skin is also composed of protein but, unlike hair, it is a livingorgan. Chapters 2 and 3 discuss the biology of skin structures in detail. Theskin's outer layer, the stratum corneum, is analogous to the hair's cuticle inthat it consists of flat, hardened, keratinized cells. As with hair, severe pertur-bations in the outer protective layer of skin can result in increasing degrees ofdamage. This damage is especially prevalent at low temperature/humidity con-ditions, which can cause skin to become relatively inflexible and inelastic. Theresulting cracks and fissures in the stratum corneum can cleave the epidermisand lead to bleeding, inflammation, and infection (2). For both skin and hair,a contiguous surface structure is key to ensuring the good condition of thesubstrate.2. Compositional Elements a. Hair. In addition to the proteinaceous structure of hair, there are ad-ditional elements of composition to consider. Lipids, which are essential tomaintaining the pliability of hair, are present both in the free form and boundin cell structures. The free lipids are primarily the oily secretions of the seba-ceous glands which provide surface gloss and lubrication to the hair; however,they may also detract from its condition by making the hair appear greasy orweighed down. The structural lipids are part of the intercellular complex andare important because they help cement together the protein structures, par-ticularly in keeping the cuticle cells. It is worth noting that the intercellularspaces, where these lipids reside, may be important pathways to deliver con-ditioning agents inside the hair (1, p. 44). When these lipids are stripped fromhair, the result is that the hair becomes more brittle and prone to damage. Water is another important component in hair. Water also helps maintainpliability, which keeps the hair shafts from fracturing. Generally, the moisturecontent in hair will equilibrate to the external humidity. However, when hairis dried by heating, the water level does not equilibrate to preheating levelswithout submersion or rewetting. This phenomenon, known as histeresis(1, p. 77) can occur as a result of the heating processes commonly used in haircare (e.g., blow dryers and curling irons). b. Skin. Skin, being a living organ, has a more complex structure thanhair, but it also depends on a mixture of lipids and water to maintain its opti-mum condition. In fact, epidermal lipids account for about 10-12% of skin'sdry tissue weight. These lipids consist of phospholipids, sphingolipids, free and

4 Schueller and Romanowskiesterified fatty acids, and free and esterified cholesterol (2). For the adventur-ous reader, an in-depth biochemical review of skin lipid composition can befound in Chapter 3. Water content in skin is essential to its health. As skin ages, it loses someof its natural ability to retain water, which in turn negatively affects its con-dition. Skin conditioning products can be extremely helpful in combatingproblems resulting from lack of moisture. In addition to moisture and lipids,skin also contains materials which act as natural humectants (e.g., sodiumhyaluronate and sodium pyrollidone carboxylate). Such materials are com-monly included in formulations designed to moisturize skin. Another aspects of skin's condition related to compositional elements ispH. The skin's surface is slightly acid, with an inherent pH between 4 and 6.This value varies depending on the area of the body, however, and areas withhigher moisture tend to have higher pH value (this includes the axilla, inguinalregions, and in between fingers and toes) (3). This \"acid mantle,\" as it is re-ferred to, assists the body in warding off infection. Therefore, proper pH is anindicator that skin is in good condition. It is important that the chemist recognize the role these compositional ele-ments (lipids, moisture, and acid/base groups) play in determining the condi-tion of hair and skin. Conditioning formulations should strive to maintain theproper balance of these elements.3. Appearance a. Hair. Appearance is another significant indicator of the condition ofhair and skin. Shine is one visual aspect that is strongly associated with the\"health\" of hair. The term \"health\" is somewhat paradoxical, considering thathair is not composed of living tissue. Nonetheless, one major marketer hasbeen quite successful with the claim that its products result in \"hair so healthyit shines.\" Regardless of the claims, shine is really the end result of several ofthe processes/factors described in the preceding sections (i.e., smoothness ofsurface structure and the presence of the appropriate levels of lipids andmoisture). Although definitions vary somewhat, shine, gloss, and luster can bemeasured both instrumentally and subjectively to provide an indication of thecondition of hair. On a similar note, color is also associated with the \"health\"of hair; i.e., hair that has vibrant color is assumed to be in better condition. Inreality this may not be the case, since hair color which is artificially inducedcan actually be damaging to the hair. b. Skin. While shine or gloss per se may not necessarily be a desirablegoal for skin conditioners, it may be an advantage for a facial moisturizer toleave the skin with a \"healthy glow.\" We note that \"healthy\" appearanceclaims make more sense when directed to skin, since that is a living organ.Another visual indicator of the quality of skin condition is its color. Color is

Introduction 5an important indicator because dry skin can take on a whitish or grayish castas light is scattered by the loose scales of the stratum corneum; in blacks thisgives skin an \"ashy\" appearance (2). Severely dry skin may have a reddenedor cracked appearance, which serves as a visual cue to its poor condition. Appearance is a key factor of hair and skin condition that should not betaken lightly. By addressing problems with the substrate's structural and com-positional elements, it is likely that its appearance will improve as well. Fur-thermore, there may be additional visual cues the formulator may be able toimpart which will reinforce the impression of such a healthy condition (artifi-cial hair color might be one such example).4. Tactile Perception a. Hair. Tactile sensations are extremely important barometers of hairand skin condition. For hair, conditioning agents can augment the soft feelthat a smooth cuticle and proper moisture/lipid balance produces. Even whenhair has been significantly damaged, i.e., when the cuticle scales are raised orabraded, conditioning agents can ameliorate the rough feel that normallyaccompanies this condition. In this regard, conditioning agents can givesignals on wet hair as well as dry. For example, some conditioning agents (e.g.,volatile silicones) are designed to provide transitory lubrication while hair iswet. Hopefully, in addition to providing a temporary improvement in the feelof the hair, the formulator will be able to provide some form of long-term aid(such as providing substantive lubrication) which will lessen the likelihood thatfurther damage will occur during subsequent styling processes. b. Skin. The sensations of touch are particularly critical when evaluatingthe condition of skin. This is somewhat ironic considering that the sensorymechanisms for touch reside in the skin itself. Skin that feels rough or dry tothe touch is, almost by definition, in poor condition. This rough feel has beenquantified by both instrumental and subjective methods. Comparative studieshave been conducted on skin roughness using a variety of methods such asimage analysis, as well as in-vivo skin testing techniques (4). Relieving per-ceived dryness is a \"must\" for skin conditioning products. In fact, Idson refersto skin conditioning as \"dry skin relief which is achieved primarily by addingmaterials to maintain or restore the elasticity or flexibility of the homy layer.This approach requires the surface of the skin be hydrated with water (orwater-miscible agents) or that it is lubricated and occluded with water-insol-uble agents (2). Consumers' perception of the dry feel of their skin is also an importantconsideration, although one might question whether such self-diagnosis isrelevant to true skin conditioning. We would respond to this issue in two ways.First, in the cosmetic industry, often perception is reality. If consumers feelthat a certain product is providing conditioning properties, no matter how

6 Schueller and RomanowskItechnically accurate this perception is, they are likely to be satisfied with thatproduct. Second, numerous scientific studies have correlated consumer per-ception with objective measurements. For example, one study found goodcorrelation between consumers' assessment of skin condition and actual meas-urement of sebum control. Another found a high correlation between per-ceived skin oiliness and skin surface lipid quantity. Finally, a good correlationalso exists between perceived smoothness/roughness and measured transepi-dermal water loss (TEWL) and skin surface morphology (5). In addition to surface texture-related tactile sensations, itching is anothersensation of interest. Technically known as pruritus, a strong itching sensationis especially common as the aging skin loses some of its hygroscopic nature (2).By improving general skin condition, conditioning products can ease the fac-tors which cause itching. Although these tactile sensations are perhaps themost subjective indicators of skin condition, they are also perhaps the mostmeaningful to consumers.5. Physical Properties a. Hair. Ultimately, deterioration of the hair shaft will be measurable interms of specific physical properties. These physical properties represent an-other aspect of the hair's condition, and they reveal aspects that are not nec-essarily reflected by the components discussed previously. As we have noted,degeneration of the hair's condition can be assessed by examining its surfacestructure, measuring depletion of lipids or moisture, or even simply touchingor observing its surface. But none of these evaluations can determine howeasily the hair will break or how its frictional properties have been affected.By objectively measuring the actual physical properties of hair, additional in-sight can be gained into its condition. Properties of interest include tensilestrength, frictional characteristics, and assembly properties of bulk hair. Tensile strength is a measurement of how the strength of hair and howprone it is to breakage. A number of instruments are used commercially toevaluate the tensile properties of hair (1, p. 299). The frictional characteristicsof the hair's surface are a good measure of how much damage it has endured.Frictional forces can be measured instrumentally and are affected by a varietyof factors including the diameter of the hair, ambient humidity, and the degreeto which the hair has been damaged (1, p. 335). The bulk properties of assem-bled hair fibers can also provide further insight into the hairs' condition. Theseinclude measurements of body or volume, manageability, and combing prop-erties (1, p. 359). Electrical conductivity measurements can quantify the de-gree to which hair will experience \"flyaway,\" which is the result of a buildupof static electric charges. b. Skin. The condition of skin can similarly be evaluated using physicalmeasurements. Tensile strength is not as relevant as it is in the case of hair,

Introduction 7but elasticity measurements are commonly employed as a barometer of skincondition. A general reduction in skin elasticity is thought to be one of theprimary causes of wrinkles, and therefore is a major indicator of skin con-dition (6). One instrumental method for quantifying skin elasticity employs ahand-held probe which measures the suction force required to life a 2-mm areaof skin (7). As with hair, friction properties of skin can provide informationon its condition. Friction is a function of specific desquamation, where theupper layers of the skin are defatted and dehydrated. When this happens,the cells may stick together and come off in clumps. An object moving acrossthis roughened, dry surface will experience increased friction (2). Frictionalforces can be measured and correlated with morphology. Finally, we mentionthat electrical conductivity is an important physical measurement in assessingthe moisture level of skin, which in turn is crucial in evaluating the skin'scondition. A number of commercial instruments are commonly used for thispurpose. When these five components (structure, compositional elements, appear-ance, tactile sensations, and physical properties) are looked at together, theyform a multidimensional picture of the condition of the hair or skin. Of course,depending on the nature of the surface and the type of conditioning effectbeing sought, one or more of them may be more important than the others. Itis important for the chemist to realize that their conditioning formulationsshould address the appropriate areas. The specific performance objectives ofthe product being formulated should be carefully compared to the compo-nents of conditioning as outlined in this chapter to suggest formulation ap-proaches the chemist can use to ensure the product is successful. Refer toChapter 12 for an expanded discussion of the philosophy of formulating con-ditioning products.II. CONDITIONING QUESTIONS—WHO, WHAT, WHERE, AND WHYFor our definition of conditioning to be useful to the chemist during theformula development process, additional questions must be asked to expandupon what is really meant by conditioning. When cosmetic chemists deal withthe challenge of formulating a product intended to condition hair or skin, theymust first have a firm grasp on what is required of that product. They mustunderstand how the product should look, smell, and feel; how expensive theformula should be, the type of packaging it will be in, and a myriad of otherdetails. But first and foremost, they must understand what kind of conditioningit is expected to deliver, To know this, the chemist needs to know the answerto several other questions first.

Schueller and RomanowskiA. Toward Whom Is the Conditioning Benefit Targeted?Even with an understanding of these components of conditioning, formulatingchemists must understand the context in which conditioning applies. The firstquestion is: \"Who is asking the question?\" This may sound a bit flippant, butit really is an important point, because the level of knowledge, sophistication,and experience of the inquiring party will help determine the answer. Idsonpoints out that dry skin, for example, \"means different things dependingwhether one is a sufferer, a dermatologist, a cosmetic manufacturer, or ageneticist\" (2). For example, a consumer's awareness of conditioning may belimited to recognizing that a rough patch of skin, e.g., on the elbow, is softened.It is possible that simple application of a conditioning oil may be enough tosatisfy this expectation. The marketing brand manager in charge of the projectmay have similar expectations. On the other hand, a chemist or dermatologistmay expect conditioning agents to measurably improve the moisture contentof skin. In this case, more effective moisturizing agents such as occlusives orhumectants may be required. It is important to recognize that the term \"con-ditioning\" can have different meanings to different audiences. This point isechoed by Professor Dikstein, who notes that in seeking a moisturizing prod-uct, the consumer may really be looking for \"a product that replenishes skinoils.\" This may be the case even though technically such a product may notactually reduce dryness or increase moisture content. The subjective elementshould not be overlooked (5).B. What Kind of Conditioning Is the Product Intended to Do?As noted earlier, numerous terms are used by professionals and lay people todenote conditioning. Conditioning skin products can be moisturizers, toners,exfolliants, etc., while hair care products can be moisturizers, detanglers, an-tistatic, hydrators, and so forth. The intended purpose of the product will de-termine the type of formula that is appropriate. All conditioning productsmust address some, or all, of the five components of conditioning outlinedabove. The key is for the chemist to understand what kind of conditioning isrequired and to ensure that the formulation addresses the appropriate condi-tioning needs.C. Where Is the Product to Be Used?Another key question to ask is: \"Where is the conditioning effect to takeplace?\" Is it targeted toward hair or skin? The requirements of these two sub-strates are quite different (these differences are reviewed in detail in Chapters2 and 3). Even more specific, but less obvious, is the question: \"What part of

Introduction 9the skin or hair is being conditioned?\" The conditioning requirements of roughelbows are quite different than those of the delicate skin around the eyes.Likewise, frayed or split ends of hair may have different requirements than theoilier hair close to the scalp. The chemist needs to understand the particulartarget area for the product before being able to select appropriate condition-ing agents.D. Why Is Conditioning of This Product Required?This leads us to the next question, which is: \"Why is conditioning being in-cluded as part of this product profile?\" This is a very important question giventhat conditioning may not be the primary purpose of the product. For example,a hand and body lotion has different conditioning requirements than a condi-tioning nail polish remover. While both are claimed to be \"conditioning,\" theexpectations are quite different. The requirements for the nail polish removermay be satisfied as long as the nail and the surrounding tissue is somewhatrefatted and protected from the lipid-stripping action of the solvents that theproduct may employ to dissolve the polish. The hand and body lotion may needto significantly increase the moisture content of the skin. Conditioning claimsare often made as a secondary benefit; understanding the role of conditioningagents in the product will help the chemist decide on appropriate agents toinclude. The questions discussed above may be best answered in the form of a com-prehensive description of the product. This \"product profile\" should clearlyspell out the expectations for the product. The use of product profiles in for-mulating conditioning products is discussed in Chapter 12. Once the chemistknows the who, what, where, and why of conditioning, he or she can begin tomake meaningful choices as to which conditioning agents are best suited fora given product.III. FORMAT OF THE BOOKAs mentioned at the beginning of this chapter, this book is organized into threeparts in order to present a thorough and practical look at the subject of con-ditioning agents. These parts discuss the physiological reasons why skin andhair need to be conditioned, the chemical compounds that can provide condi-tioning, and methods for developing and testing conditioning products. The text begins with a description of the biology of skin and hair and dis-cusses the physiological factors that create the need for conditioning. Chapter2 provides a general look at the structure of both hair and skin and introducessome of the strategies employed for conditioning these surfaces. It also ex-pands on the definition of conditioning, providing an appropriate background

10 Schueller and RomanowskIfor the rest of the book. Chapter 3 examines the composition of skin, particu-larly biological lipids, in detail. It also describes the various components thatare naturally present in skin and suggests mechanisms by which they are in-volved in conditioning skin. The second part of this volume discusses the specific ingredients which areused as conditioning agents. The ingredients have been chosen as representa-tives of the different classes of materials actually used as conditioning agentsin personal care formulations. Each ingredient chapter provides a generalbackground on the materials in question, including a definition, description ofchemical and physical properties, brief history, method of manufacture, andbasic function. Additionally, information is provided about the way these ma-terials interact with hair and skin surfaces and information regarding their usein formulations. Finally, each chapter speculates on the future of these rawmaterials and what derivative materials may be developed. The first three chapters in Part Two deal with conditioning agents whichare designed primarily to improve the condition of skin, though hair applica-tions are also considered. Chapter 4 discusses occlusive agents, which are ma-terials that condition by creating a moisture barrier between the biologicalsurfaces and air. Petrolatum is used as the classic example of an occlusiveagent. Humectants, which are materials that condition by binding moisture,are the subject of Chapter 5. These conditioning agents include materials suchas glycerin and propylene glycol. Chapter 6 examines the chemical and physi-cal properties of emollients. These hydrophobic materials are used to imparta specific feel to hair and skin. Chapter 7 looks at proteins and how they can provide conditioning benefitsto both skin and hair. Data are given which show real conditioning benefitsfrom the use of these materials. The next two chapters discuss the growing areaof silicone conditioning agents. The reactions to produce long-chain Siloxanepolymers and applications for these materials in personal care products areprovided in Chapter 8. Chapter 9 examines the latest in cutting-edge siliconederivative technology. Chapter 10 discusses conditioning through the use of cationic surfactants.These materials bond ionically to skin and hair to improve their condition.This section concludes with Chapter 11, which is about the various types ofpolymers used for conditioning. Much research is going on in this area of poly-mers, and it is anticipated that these materials will continue to find expandeduse in formulations. The third part of the book deals with the formulation and evaluation ofpersonal care products designed to condition hair and skin. The practical as-pects of formulating conditioning products is discussed in Chapter 12. It pre-sents a practical method for designing a product from the idea stage all theway through to production. The last two chapters provide a look at methods

Introduction 11for testing the effectiveness of conditioning products. Chapter 13 describesclassic procedures for testing hair, along with the latest evaluation methods.Chapter 14 examines test methodologies for skin. It describes various methodsof evaluating skin condition including both in-vivo and in-vitro testing.REFERENCES 1. Robbins CR. Chemical and Physical Behavior of Human Hair. 3d ed. New York: Springer-Verlag, 1994:212. 2. Idson B. Dry skin moisturizing and emolliency. Cosmet Toilet 1992 (July); 107(7): 70. 3. Robbins CR. Chemical and Physical Behavior of Human Hair. 3d ed. New York: Springer-Verlag, 1994:44. 4. Ibid., p. 77. 5. Idson, B. Dry skin moisturizing and emolliency. Cosmet Toilet 1992 (July); 107(7): 71. 6. Yosipovitch G, Maibach H. Skin surface pH: a protective acid mantle. Cosmet Toilet 1996 (Dec); 111(12):101. 7. Idson, B. Dry skin moisturizing and emolliency. Cosmet Toilet 1992 (July); 107(7): 70. 8. Schrader K, Bielfeldt S. Comparative studies of skin roughness measurements by image analysis and several in vivo skin testing measurements. J Soc Cosmet Chem 1991; 42(6):385. 9. Idson B. Dry skin moisturizing and emolliency. Cosmet Toilet 1992 (July); 107(7): 69.10. Ayala L, Dikstein S. Objective measurement and self-assessment of skin care treat- ments. Cosmet Toilet 1996 (June); 111(6):91.11. Idson, B. Dry skin moisturizing and emolliency. Cosmet Toilet 1992 (July): 107(7): 69.12. Robbins CR. Chemical and Physical Behavior of Human Hair. 3d ed. New York: Springer-Verlag, 1994:299.13. Ibid., p. 335.14. Ibid., p. 359.15. Imokawa G, Takema Y. Fine wrinkle formation: etiology and prevention. Cosmet Toilet 1993 (Dec); 108(12):65.16. Takema Y, Yorimoto K. The relationship between age related changes in the physical properties of wrinkles in human facial skin. J Soc Cosmet Chem 1995; 46:163-173.17. Idson B. Dry skin moisturizing and emolliency. Cosmet Toilet 1992 (July); 107(7): 70.18. Ibid.19. Ayala L, Dikstein S. Objective measurement and self-assessment of skin care treat- ments. Cosmet Toilet 1996 (June); 111(6):96.

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2Biology of the Hair and SkinZoe Diana DraelosWake Forest University School of Medicine, Winston-Salem, andDermatology Consulting Services, High Point, North CarolinaI. INTRODUCTIONA. The Need to ConditionThe hair and skin are responsible for the entire visual appearance of both menand women. All visible major body surfaces are covered with some type of hairor skin, important for healthy functioning of the body and creation of an iden-tifiable image of cosmetic value. An understanding of the biology of hair andskin is key to developing products designed to maintain the optimum cosmeticappearance of the individual. This chapter focuses on those aspects of hair andskin physiology that affect the use and development of conditioning agents forthe hair and skin. The hair and skin are different from other body organs in that the hair andskin create the milieu suitable for optimum functioning of other body organsand systems while sustaining contact with the external environment. Condi-tioning agents are necessary because humans live in an outdoor global envi-ronment, with wide variations in humidity and temperature, and have createdindoor environments that are not always optimal for hair and skin functioning.Thus, conditioning agents are the means by which people can endure tremen-dous climatic variability without an increase in skin disease processes or adecrease in the cosmetic value of the hair or skin. 13

14 Draelos Conditioning of the hair and skin must be a continuous process, however,since both of these substances are in a cycle of constant renewal and shedding.Unlike vital organs, such as the heart, liver, or kidneys, in which limited cellularrenewal can occur, the skin completely replaces its outermost layer on a bi-weekly basis, while hair growth occurs at a rate of 0.35 mm/day (1). This leadsto a key difference between hair and skin. Skin is basically a living organ witha few sloughed cells on the surface, while hair is basically a dead organ with afew live cells deep within the skin. Thus, conditioning agents for skin can affectthe homeostatic processes of growth and repair by supplementing the body'sown genetically inherited renewal mechanisms. This contrasts with condition-ing agents for hair, which have no effect on growth and cannot affect cellularrepair. Hair conditioners can only temporarily improve the cosmetic appear-ance of damaged hair and must be reapplied as removal occurs. With thesebasic concepts in mind, the discussion can now turn to the details of the struc-ture and biology of the hair and skin.B. Historical PerspectiveThe hair and skin are unique in that they are body structures readily accessiblefor scientific observation, yet much remains to be understood regarding theirgrowth and regulation. The first article detailing the development of the skinwas published by Albert von Kolliker, a Swiss anatomy professor in Wurzburg,in 1847. The first dermatologist to study the subject was P. G. Unna of Ham-burg in 1876 (2). A student in Unna's clinic, Martin Engman, Professor ofDermatology, Washington University, St. Louis, became interested in theembryology and development of the hair follicle. His work was furthered byC. H. Danforth, Mildred Trotter, and L. D. Cady, who published the founda-tion work on hair formation in 1925 (3). Further work on the developmentof the hair follicle continued with Pinkus (1958) (4), Sengel (1976) (5), andSpearman (1977) (6,7). New observational methods of evaluating the hair andskin have led to the current understanding of the biology of the hair and skinto be discussed.ii. BIOLOGY OF THE SKINThe skin comprises the largest organ of the body, representing an amazingstructure that encases, contours, and conforms to the organism within. It pro-vides a physical and chemical barrier while protecting against environmentalinsults. It contains numerous transducers sending a continuous array of sen-sory information to the brain for processing. Lastly, the skin is responsible forexternal appearance, creating a unique and recognizable image identifiable toothers.

Biology of the Hair and Skin 15A. Development and Anatomy (Figure 1)The skin develops at 30 to 40 days gestation and consists of two primary layers:the epidermis and dermis (8,9). The epidermis represents the external layerof skin and is composed mainly of keratinocytes, named for their primary pro-teinaceous component, known as keratin. The keratinocytes are held togetherby cellular attachments or desmosomes. The epidermis also contains melano-cytes, which produce a pigment known as melanin, and specialized immunecells, known as Langerhans cells. It is divided into several distinct functionallayers: the basal cell layer (stratum germinativum), from which all new cellsare derived; the spinous layer (stratum spinosum); the granular cell layer(stratum granulosum); and the horny cell layer (stratum comeum) (10). Thestratum corneum is the outermost layer of the epidermis, comprised of 15 to20 cell layers, functioning to protect the underlying tissues and nerves fromdamage. Products aimed at conditioning the skin must have significant impacton the stratum corneum. The zone between the epidermis and the underlying dermis is referred toas the basement membrane zone or the epidermal-dermal junction (11).Below this lies the dermis, which is a moderately dense fibroelastic connec-tive tissue composed of collagen fibers, elastic fibers, and an interfibrillar gel ofglycosaminoglycans. Collagen is synthesized by the dermal fibroblasts and isresponsible for the strength and 77% of the fat free dry weight of the skin.Interspersed between the collagen bundles is a network of elastic fibers thatallow the skin to resist and recover following mechanical deformation (12). Hair shaft Epidermis DermisHairfollicle Subcutaneous fatFigure 1 Structure of the skin, demonstrating the relationship between the epider-mis, dermis, and follicular units.

16 Draelos The dermis is divided into two parts: the papillary dermis and the reticulardermis (13). The papillary dermis contains smaller collagen and elastic fibersthan the reticular dermis, but encloses the extensive circulatory, lymphatic,and nervous system of the skin. It also contains fibronectins, which function asadhesive proteins to attach fibroblasts to collagen, and abundant glycosami-noglycans, also known as ground substance, which are anionic polysaccha-rides. The major glycosaminoglycans are hyaluronic acid, chondroitin sulfate,dermatan sulfate, and heparin sulfate. They function to maintain adequatewater homeostasis within the skin and influence flow resistance to solutes. Inessence they are the natural moisturizing substances of the skin, necessary toprevent cutaneous dehydration. They comprise only 0.2% of the dry weight ofthe skin, but are capable of binding water in volumes up to 1000 times theirown. The reticular dermis is formed of dense collagenous and elastic connectivetissue and does not contain many cells or blood vessels or glycosaminoglycans.It overlays the subcutaneous fat, which provides padding for cutaneous me-chanical insults and acts as a reservoir for extra caloric intake.B. Growth CycleThe skin is in a constant state of renewal as the basal cells divide and replenishaging cells, which are sloughed off from the stratum comeum at the surface.Thus, skin has a tremendous ability to regenerate. Acute injuries to the epi-dermis alone can be completely repaired without scarring, but dermal injuriesusually result in the production of scar tissue which is functionally and cos-metically inferior to the uninjured skin. The transit time of cells from the lower stratum corneum to desquamationis approximately 14 days, meaning that a new skin surface is present every 2weeks. Products that are designed to affect the skin surface must be continuallyapplied, since the skin is in a constant state of flux. Complete, full-thicknessrenewal of the skin from the basal cell layer to the stratum corneum requires45 to 75 days, meaning that the epidermis completely replaces itself every 2months (14). Thus products that are designed to affect skin growth must beapplied for at least 2 months for a visual impact.C. Collagen CompositionCollagen forms the major component of the skin and is synthesized as threepolypeptide chains by the fibroblasts. The three chains form a triple helix ofapproximately 1000 amino acids in length, with glycine serving as every thirdunit accompanied by abundant hydroxyproline and hydroxylysine. Crosslink-ing between the chains occurs at the sides, not at the ends, accounting for thegreat strength of the collagen fibers (15). At present, 14 different types of

Biology of the Hair and Skin 17collagen have been identified, each with a different function within the skinand body.D. Cutaneous Structures Relevant to Skin ConditionThree important structures warranting further comment contribute to the con-dition of the skin: the stratum comeum, the stratum spinosum, and the seba-ceous gland. A more detailed discussion of the numerous structures within theskin is beyond the scope of this chapter. (Further information can be obtainedfrom the excellent text by Lowell A. Goldsmith entitled Physiology, Biochem-istry, and Molecular Biology of the Skin, 2nd edition, New York, Oxford Uni-versity Press, 1991.) The stratum comeum is the outermost layer of the epidermis. It is respon-sible for protection and is affected by conditioning substances. It is formed bycorneocytes which are highly resistant to degradation due to the crosslinkingof a soluble protein precursor involucrin, which is acted upon by epidermaltransglutaminase. The final product is a 65% insoluble cysteine-rich disulfidecrosslinked protein (16). The stratum comeum presents the first barrier topercutaneous absorption, but is subject to degradation through hydration, re-moval through tape stripping, protein denaturation through the application ofsolvents, and alteration of the lipid structure (17). The stratum spinosum is important because it is responsible for productionof submicroscopic lamellar granules approximately 100 by 300 nm in diameter.These lamellar granules, also called membrane-coating granules or Odlandbodies, are seen at the outer surface of the flattening cells that form the stra-tum granulosum and are eventually extruded into the extracellular compart-ment between the lowermost cells of the stratum corneum. Their internalstructure is highly ordered into sheets which hold sterols, lipids, lipases, gly¬cosidases, and acid phosphatase (18). The lipases are able to convert polarlipids into nonpolar lipids which coalesce to form crystalline sheets within theintercellular spaces between the corneocytes, thus forming a waterproof bar-rier to percutaneous absorption (19). The acid phosphatases, on the otherhand, are necessary to aid in desquamation of old corneocytes by dissolvingthe intercellular cement. Thus, the lamellar granules are extremely importantin the condition of the external surface of the skin (20). The last important structure to discuss relevant to the condition of the skinis the sebaceous gland, which is responsible for production of sebum. Thesebaceous glands are largest on the face, scalp, mid-back, and mid-chest, pro-ducing secretions released into the sebaceous duct which connects the glandto the follicular canal. Sebaceous secretions are produced in response to hor-monal stimuli. Sebum has many functions on the skin: it functions as a mois-turizer, it enhances barrier properties, and it may act as an antifungal and

18 Draelosantibacterial. It is composed of triglycerides (60%), free fatty acids (20%), andsqualene (10%). Sebum, in combination with perspiration from the eccrineglands and environmental dirt, coat the external surface of the skin.E. Epidermal LipidsThree intercellular lipids are implicated in epidermal barrier function: sphin¬golipids, free sterols, and free fatty acids (21). In addition, it is thought thatthe lamellar bodies, discussed previously (Odland bodies, membrane-coatinggranules, cementsomes), containing sphingolipids, free sterols, and phospho-lipids, play a key role in barrier function and are essential to trap water andprevent excessive water loss (22,23). The lipids are necessary for barrier func-tion, since solvent extraction of these chemicals leads to xerosis, directly pro-portional to the amount of lipid removed (24). The major lipid by weight foundin the stratum corneum is ceramide, which becomes sphingolipid if glycosy-lated via the primary alcohol of sphingosine (25). Ceramides possess the ma-jority of the long-chain fatty acids and linoleic acid in the skin. Other lipids present in the stratum corneum include cholesterol sulfate,free sterols, free fatty acids, triglycerides, sterol wax/esters, squalene, andn-alkanes (26). Cholesterol sulfate comprises only 2-3% of the total epidermallipids, but is important in comeocyte desquamation (27). It appears that cor-neocyte desquamation is mediated through the desulfatation of cholesterolsulfate (28). Fatty acids are also important, since it has been demonstratedthat barrier function can be restored by topical or systemic administration oflinoleic acid-rich oils in essential fatty acid-deficient rats (29).F. Physical PropertiesThe skin is a tremendously distensible material that adapts quickly to change.This is necessary to accommodate the many alterations in shape required formovement and growth of the human body. Thus, the skin becomes more elasticover time as it is subjected to increasing tensile and torsional forces. Elastictissue accounts for only 5% of the dermal connective tissue by weight andthus cannot contribute significantly to the viscoelastic properties of the skin.Rather, it is thought that the collagen fibers slip over one another and becomealigned through a change in bonding or molecular realignment (30). The ten-sile strength of collagen is tremendous, with a single 1-mm fiber able to with-stand a static load of up to 20 kg. However, the ability of the skin to respond to mechanical change decreaseswith age. Some of this change is due to ultraviolet light exposure (extrinsicaging), while other change is due to the natural effects of aging (intrinsic aging)and the effects of long-term oxidative damage on the skin. Biochemical changesnoted include decreased glycosaminoglycan content, leading to thinning of the

Biology of the Hair and Skin 19dermis, which predisposes to easy bruisability, wrinkling, and dehydration ofthe skin. The collagen fibers also change as soluble collagens decrease whileinsoluble collagens increase (31). This tremendous ability of the skin to renew itself and respond to changecontrasts with hair, a nonliving tissue that cannot adapt or repair damage.III. BIOLOGY OF THE HAIRHair represents a structure that has lost much of its functional significancethrough evolutionary change, yet it is important to aid in the transduction ofsensory information and to create gender identity. The value of hair, however,cannot be underestimated from a social and emotional standpoint, since theappearance of the scalp hair is an intimate part of the perception of self.A. Development and AnatomyHair follicles are formed early in development of the fetus, with eyebrow,upper lip, and chin follicles present at week 9 and the full complement offollicles present by week 22. At this time, the total body number of 5 millionfollicles is present, with 1 million on the head, of which 100,000 are on the scalp(32). No additional follicles are formed during life. As body size increases, thenumber of hair follicles per unit area decreases. For example, the averagedensity of hair follicles in the newborn is 1135 per square centimeter, drops to795 per square centimeter at the end of the first year, and decreases to 615 persquare centimeter by the end of the third decade. Continued hair follicle den-sity decreases occur on the scalp with balding (33). The hair grows from follicles which resemble stocking-like invaginations ofthe epithelium enclosing an area of dermis known as the dermal paillae (Fig-ure 2). The area of active cell division, the living area of the hair, is formedaround the dermal papillae and is known as the bulb, where cell division occursevery 23 to 72 hr (34). The follicles slope into the dermis at varying angles,depending on body location and individual variation, and reside at varyinglevels between the lower dermis and the subcutaneous fat. In general, largerhairs come from more deeply placed follicles than do finer hairs (35). Anarrector pili muscle attaches to the midsection of the follicle wall and ends atthe junction between the epidermis and the dermis. In some body areas, asebaceous gland (oil gland) and an apocrine gland (scent gland) attach abovethe muscle and open into the follicle. The point at which the arrector pilimuscle attaches is known as the hair \"bulge\" and is considered to be the sitewhere new matrix cells are formed and the hair growth cycle initiated. It takesapproximately 3 weeks for a newly formed hair to appear at the scalp surface(36).

20 Draelos sebaceous gland arrector pili muscleinner root sheathouter root sheath dermal papillaAnagen Catagen TelogenFigure 2 Schematic drawing demonstrating the relationship of the hair follicle to theskin at various stages of growth. The sebaceous gland is important to the maintenance of the grown hairshaft, as it produces sebum, a natural conditioning agent. Approximately 400to 900 glands p>cr square centimeter arc located on the scalp and represent thelargest glands on the body (37). Sebum, composed of free fatty acids and neu-tral fats, is produced in increased amounts after puberty in males and females.In the female, sebum production declines with age, but this effect is less promi-nent in males.B. Growth CycleHair growth continues on a cyclical basis, with each hair growing to geneticand age-determined length, remaining in the follicle for a short period of timewithout growth, and eventual shedding followed by regrowth (Figure 2) (38).The growth phase, known as Anagen, lasts approximately 1000 days, and thetransitional phase, or Catagen, about 2 weeks (39). The resting phase, or telo-gen, lasts approximately 100 days. Scalp hair is characterized by a relativelylong anagen and a relatively short telogen, with a ratio of anagen to telogenhairs of 90 to 10 (40). Only 1 % or less of the follicles are in catagen at any giventime. Thus, the healthy individual loses 100 hairs per day. It is estimated thateach follicle completes this cycle 10 to 20 times over a lifetime, but the activityof each follicle is independent. The mechanism signaling the progression from one phase to the next isunknown, but the duration of anagen determines the maximum length to

Biology of the Hair and Skin 21which the hair can be grown. Hair growth can be affected by physical factors(severe illness, surgery, weight change, pregnancy, hormonal alterations,thyroid anomalies, dermatological disease) and emotional factors, but isunaffected by physical alterations limited to the hair shaft (shaving, curling,combing, dyeing, etc.). Plucking of the hairs from resting follicles can stimulategrowth, however (41).C. CompositionHair is composed of keratin, a group of insoluble cystine-containing helicoidalprotein complexes. The hair is made up of an amorphous matrix that is highin sulfur proteins and in which the keratin fibers are embedded. These proteincomplexes, which form 65-95% of the hair by weight, are extraordinarily re-sistant to degradation and are thus termed \"hard,\" as opposed to the \"soft\"keratins that compose the skin (42). Under X-ray crystallography, the hairfiber helix has an alpha diffraction pattern, which changes to a beta diffractionpattern as the hair is stretched and the helix is pulled into a straight chain.D. Structure (Figure 3)The hair is composed of closely attached, keratinized fusiform cells arrangedin a cohesive fiber (43). The greatest mass of the hair shaft is the cortex, withsome shafts also possessing a medulla. The cortex consists of closely packedspindle-shaped cells with their boundaries separated by a narrow gap whichcontains a proteinaceous intercellular lamella that is thought to cement thecells together (44). Thus, the cortex contributes to the mechanical propertiesof the hair shaft. The medulla is formed from a protein known as trichohyalin.The function of the medulla remains unknown; however, it contains glycogen(a form of glucose) and melanosomes (pigment packages). In some areas themedulla cells appear to dehydrate and air-filled spaces are left behind. Thickerhairs, such as scalp hairs, are more likely to contain a medulla than are finerbody hairs (45). Surrounding this structure is a protective layer of overlapping, kerati-nized scales known as the cuticle, which can account for up to 10% of the hairfiber by weight (46). The free edges of the cuticle are directed outward,with the proximal edges resting against the cortex. The cuticular scales arearranged much like roofing shingles to provide 5 to 10 overlapping celllayers, each 350 to 450 nm thick, to protect the hair shaft along its entirelength. The cell structure of the cuticle is composed of three major layers: theA layer, the exocuticle, and the endocuticle (Figure 4). It is the clear A layer,which is high in sulfur-containing proteins, that protects the hair from chemi-cal, physical, and environmental insults (47). From a hair conditioning stand-point, an intact cuticle is essential to the cosmetic value of the hair, and the

22 DraelosFigure 4 Layers of the cuticle.

Biology of the Hair and Skin 23Figure 5 The cross-sectional shape of the hair shaft determines its appearance, physi-cal properties, and conditioning needs.goal of hair conditioning products is to enhance and restore order to this hairshaft layer.E. ShapeThe degree of curl found in a hair shaft is related directly to its cross-sectionalshape, which determines its cosmetic appearance and conditioning needs (Fig-ure 5). Caucasoid hair has an elliptical cross section accounting for a slightcurl, while Mongoloid hair has a circular cross section leading to straight hair(48). Negroid hair is identical to Caucasoid and Mongoloid hair in its aminoacid content, but has a slightly larger diameter, lower water content, and, mostimportant, a flattened elliptical cross-sectional shape (49). It is the asymmetryof this cross section that accounts for the irregular kinky appearance of Blackhair. Hair that is wavy or loosely kinked has a cross-sectional shape in betweena circle and flattened ellipse. The cross-sectional shape of the hair fiber accounts for more than the de-gree of curl; It also determines the amount of shine and the ability of sebumto coat the hair shaft (50). Straight hair possesses more shine than kinky hairdue to its smooth surface, allowing maximum light reflection and ease of se-bum movement from the scalp down the hair shaft. The irregularly kinked hairshafts appear duller, even though they may have an intact cuticle, due to roughsurface and difficulty encountered in sebum transport from the scalp, eventhough Negroid hair tends to produce more sebum. The shape of the hair shaft also determines grooming ease. Straight hair iseasiest to groom, since combing friction is low and the hair is easy to arrange

24 Draelosin a fashionable style. Kinky hair, on the other hand, demonstrates increasedgrooming friction, resulting in increased hair shaft breakage. Kinky hair alsodoes not easily conform to a predetermined hair style, unless the shafts areshort.F. Physical PropertiesThe physical properties of the hair shaft are related to its geometric shape andthe organization of its constituents. The cortex is largely responsible for thestrength of the hair shaft, but must have an intact cuticle to resist externallyapplied mechanical stresses. The most important mechanical property of hairis its elasticity, allowing stretching deformation and a return to normal condi-tion. Hair can be stretched to 30% of its original length in water and experienceno damage, but irreversible changes occur when hairs are stretched to between30% and 70% of their original length. Stretching to 80% of original lengthgenerally results in hair shaft fracture (51). The water content of the hair shaft is important to its physical and cosmeticproperties. The porosity of the hair shaft is about 20%, allowing a weight in-crease of 12-18% when soaked in water. The absorption rate is very rapid, with75% of the maximum absorbable water entering the hair shaft within 4 min(52). Water absorption causes hair shaft swelling, making wetting the first stepin cosmetic hair procedures that require entry into the hair shaft. Wetting andsubsequent drying of the hair shaft in a predetermined position is also basic tohair styling. Friction effects on the hair shaft are also an important consideration. It hasbeen shown that wet straight hair has a higher combing friction than dry straighthair (53); however, wet hairs are excellent conductors of electricity while dryhairs conduct electricity poorly. Thus, static electricity preferentially affectsdry hair, since the ions are not moving. The presence of static electricity createsa manageability problem known as \"flyaways,\" since the individual hair shaftsrepel one another. Static electricity can be reduced by decreasing hair friction,combing hair under cooler conditions, or decreasing the resistance of hairfibers by increasing hair moisture. The preceding discussion has focused on the specifics of the biology of theskin and hair. These ideas now must be expanded to understand how hair andskin biology affect their conditioning needs.IV. SKIN DISEASE AND CONDITIONINGA. Physiology of XerosisXerosis is a result of decreased water content of the stratum corneum, whichleads to abnormal desquamation of corneocytes. For the skin to appear and

Biology of the Hair and Skin 25feel normal, the water content of this layer must be above 10% (54). Water islost through evaporation to the environment under low humidity conditionsand must be replenished by water from the lower epidermal and dermal layers(55). The stratum comeum must have the ability to maintain this moisture orthe skin will feel rough, scaly, and dry. However, this is indeed a simplistic view,as there are minimal differences between the amount of water present in thestratum corneum of dry and normal skin (56). Xerotic skin is due to more thansimply low water content (57). Electron micrographic studies of dry skin dem-onstrate a stratum corneum that is thicker, fissured, and disorganized. It ap-pears that the scaly appearance of xerotic skin is, in part, due to the failure ofcorneocytes to desquamate appropriately. Other disease states, such as psoriasis and atopic dermatitis, also demon-strate abnormal barrier function due to ceramide distribution (58,59). In-terestingly, xerosis tends to increase with age, due to a lower inherent watercontent of the stratum corneum (60). However, this fact does not totally ac-count for the scaliness and roughness of aged skin; probably an abnormaldesquamatory process is also present (61).B. Epidermal Barrier RepairOnce the epidermal barrier has been damaged, signals must be transmittedto the intracellular machinery to initiate repair or reconditioning of the skin.Remoisturization of the skin occurs in four steps: initiation of barrier repair,alteration of surface cutaneous moisture partition coefficient, onset of der-mal-epidermal moisture diffusion, and synthesis of intercellular lipids (62). Itis generally thought that a stratum corneum containing between 20% and 35%water will exhibit the softness and pliability of normal stratum corneum (63). Perturbations within the barrier must be sensed before the onset of lamellarbody secretion and a cascade of cytokine changes associated with adhesionmolecule expression and growth factor production (64). Thus, if skin with bar-rier perturbations is occluded with a vapor-impermeable wrap, the expectedburst in lipid synthesis is blocked. However, occlusion with a vapor-permeablewrap does not prevent barrier recovery (65). Therefore, transepidermal waterloss is necessary to initiate synthesis of lipids to allow barrier repair and skinreconditioning to occur (66,67).C. Mechanisms of Moisturization and Skin ConditioningOnce skin damage has occurred and the barrier damaged, reconditioning canoccur only if the loss of moisture is retarded. This is the goal of moisturizers,which function temporarily until skin integrity can be reestablished. There arethree physiological mechanisms for rehydrating the stratum corneum: the useof occlusives, humectants, and hydrophilic matrices (68).

26 Draelos1. OcclusivesOcclusives function to condition the skin by impairing evaporation of water tothe atmosphere. They are generally oily substances through which water can-not pass. Occlusive substances can be broken down into categories (69): Hydrocarbon oils and waxes: petrolatum, mineral oil, paraffin, squalene Silicone oils Vegetable and animal fats Fatty acids: lanolin acid, stearic acid Fatty alcohol: lanolin alcohol, cetyl alcohol Polyhydric alcohols: propylene glycol Wax esters: lanolin, beeswax, stearyl stearate Vegetable waxes: carnauba, candelilla Phospholipids: lecithin Sterols: cholesterolThe most occlusive of the above chemicals is petrolatum (70). It appears, how-ever, that total occlusion of the stratum corneum is undesirable. While thetransepidermal water loss can be completely halted, once the occlusive is re-moved, water loss resumes at its preapplication level. Thus, the occlusive mois-turizer has not allowed the stratum corneum to repair its barrier function (71).Petrolatum does not appear to function as an impermeable barrier; rather, itpermeates throughout the interstices of the stratum comeum, allowing barrierfunction to be reestablished (72).2. HumectantsA dehydrated epidermis can also be conditioned through the use of humec-tants, substances which attract water, mimicking the role of the dermal gly-cosaminoglycans. Examples of topical humectants include glycerin, honey,sodium lactate, urea, propylene glycol, sorbitol, pyrrolidone carboxylic acid,gelatin, hyaluronic acid, vitamins, and some proteins (73,74). Topically applied humectants draw water largely from the dermis to theepidermis and rarely from the environment, under conditions where the am-bient humidity exceeds 70%. Water that is applied to the skin in the absenceof a humectant is rapidly lost to the atmosphere (75). Humectants may alsoallow the skin to feel smoother by filling holes in the stratum corneum throughswelling (76). However, under low humidity conditions, humectants, such asglycerin, will actually draw moisture from the skin and increase transepidermalwater loss (77).3. Hydrophilic MatricesHydrophilic matrices are large-molecular-weight substances that form a bar-rier to cutaneous water evaporation. Hyaluronic acid, a normal component of

Biology of the Hair and Skin 27the dermal glycosaminoglycans, is a physiological hydrophilic matrix, whilecolloidal oatmeal is a synthetic hydrophilic matrix.D. Mechanisms of Emolliency and Skin ConditioningSome moisturizing substances can also function as emollients by temporarilyfilling the spaces between the desquamating corneocytes (78). Emolliency isimportant because it allows the skin surface to feel smooth to the touch. Emol-lients can be divided into several categories: protective emollients, fattingemollients, dry emollients, and astringent emollients (79). Protective emol-lients are substances such as diisopropyl dilinoleate and isopropyl isostearatethat remain on the skin longer than average and allow the skin to feel smoothimmediately upon application. Fatting emollients, such as castor oil, propyl-ene glycol, jojoba oil, isostearyl isostearate, and octyl stearate, also leave along-lasting film on the skin, but they may feel greasy. Dry emollients, such asisopropyl palmitate, decyl oleate, and isostearyl alcohol, do not offer muchskin protection but produce a dry feel. Lastly, astringent or drying emollients,such as the dimethicones and cyclomethicones, isopropyl myristate and octyloctanoate, have minimal greasy residue and can reduce the oily feel of otheremollients. The skin is unique in that it produces its own conditioning agent, sebum,and can repair damage due to surfactants and solvents. Hair, on the otherhand, receives some sebum from the scalp, but externally applied conditioningagents are necessary at the ends of the hair shafts, especially if the hair is long.Conditioning of the hair is especially important because the damaged hairshaft undergoes no repair processes.V. HAIR DAMAGE AND CONDITIONINGHair damage results from both mechanical and chemical trauma that altersany of the physical structures of the hair. Conditioning agents cannot enhancerepair, since repair does not occur, but can temporarily increase the cosmeticvalue and functioning of the hair shaft until removal of the conditioner occurswith cleansing. The cuticle is the main hair structure affected by conditioningagents (80). An intact cuticle is responsible for the strength, shine, smoothness,softness, and manageability of healthy hair. A layer of sebum coating the cu-ticle also adds to hair shine and manageability.A. Mechanism of Hair DamageHealthy, undamaged hair is soft, resilient, and easy to detangle, due to thetightly overlapping scales of the cuticle (81). Cuticular loss, known as weath-ering, is due to the trauma caused by shampooing, drying, combing, brushing,

28 Draelosstyling, chemical dyeing, permanent waving, and environmental factors suchas exposure to sunlight, air pollution, wind, sea water, and chlorinated swim-ming pool water (82,83). Conditioning the hair can mitigate this hair damageby improving sheen, decreasing brittleness, decreasing porosity, and increas-ing strength.B. Mechanisms of Hair ConditioningThere are several mechanisms by which conditioners can improve the cosmeticvalue of the weathered hair shaft: increasing shine, decreasing static electricity,improving hair strength, and providing ultraviolet (UV) radiation protection.1. ShineShiny hair is visually equated with healthy hair even though the health of thehair follicle cannot be assessed due to its location deep within the scalp. Thisshine is due to light reflected by the smooth surface of the individual hair shaftsand large-diameter, elliptical hair shafts with a sizable medulla (84). Condi-tioners, such as those containing polymer film-forming agents, can increasehair shine primarily by increasing adherence of cuticular scale to the hair shaftand filling in the spaces between cuticular defects (85).2. Static ElectricityCombing or brushing of the hair allows the individual hair shafts to becomenegatively charged, creating static electricity and preventing the hair from ly-ing smoothly in a given style. Fine hair is more subject to static electricity thancoarse hair, due to the larger surface area of the cuticle. Conditioning agents,such as quaternary ammonium compounds, are able to minimize static elec-tricity electrically (86).3. StrengthConditioning of the hair can also attempt to slightly increase hair strength byallowing hydrolyzed proteins of molecular weight 1000 to 10,000 to diffuse intothe hair shaft through defects in the protective cuticular scale (87). The sourceof the protein is not as important as the protein particle size (88). However,the protein readily diffuses out of the hair shaft with cleansing, as the nonlivingstatus of the hair shaft precludes permanent incorporation. Proteins can alsobe used to temporarily reapproximate split hair shaft ends, known as trichop-tilosis, resulting from loss of the cortex, required for hair shaft strength, andexposure of the soft keratin of the medulla.4. PhotoprotectionWhile the hair is made up of nonliving material and cannot develop can-cerous changes, its cosmetic value can be diminished through excessive ex-

Biology of the Hair and Skin 29posure to the sun. Dryness, reduced strength, rough surface texture, loss ofcolor, decreased luster, stiffness, and brittleness of the hair are all precipi-tated by sun exposure. Hair protein degradation is induced by light wave-lengths from 254 to 400 nm (89). Chemically, these changes are thought tobe due to ultraviolet light-induced oxidation of the sulfur molecules withinthe hair shaft (90). Oxidation of the amide carbon of polypeptide chainsalso occurs, producing carbonyl groups in the hair shaft (91). This processhas been studied extensively in wool, where it is known as \"photoyellowing\"(92,93). Bleaching, or lightening of the hair color, is common in both brunette andblonde individuals who expose their hair to ultraviolet radiation (94). Brunettehair tends to develop reddish hues due to photooxidation of melanin pigments,while blonde hair develops photoyellowing. The yellow discoloration is due tophotodegradation of cystine, tyrosine, and tryptophan residues within theblonde hair shaft (95). This points to a need for the development of photopro-tective conditioning products for the hair.VI. CONCLUSIONS AND FUTURE DEVELOPMENTSFuture developments regarding skin and hair conditioning agents rely on abetter understanding of the biology of these structures. Only by elucidatingmechanisms for enhanced growth and repair can product development occur.A wealth of information on the mechanisms of skin barrier formation isaccumulating, leading to the realization that many disease states (atopicdermatitis, xerotic eczema) may be due to faulty sebum production and/orimproper formation of the intercellular lipids. Future dermatological researchmay find a topical method of replacing missing substances and restoringnormal function. A better understanding of defective corneocyte sloughingencountered in mature individuals is leading to the development of topicalmoisturizers designed to increase desquamation and restore a smooth skinsurface. Most hair damage occurs as a result of grooming habits and chemicalexposure for cosmetic purposes. An evaluation of hair structure and biologypoints to the need for better protective mechanisms from cuticular damageand UV damage to maintain the cosmetic value of the hair, Methods for en-hancing product substantivity for hair keratin are necessary to provide long-term protection that is somewhat resistant to cleanser removal. Through the cooperative efforts of dermatologists and cosmetic chemists,better hair and skin conditioning agents can be developed. The dermatologistneeds to elucidate the mechanism through which products can enhance func-tioning, while the cosmetic chemist needs to identify substances and developformulations to accomplish the desired end.

30 DraelosREFERENCES 1. Myers RJ, Hamilton JB. Regeneration and rate of growth of hair in man. Ann NY Acad Sci 1951; 53:862. 2. Unna PG. Beitrage zur histologic und entwickiengsgeschichte der menschlichen oberhat und ihrer anhangsgebilde. Arch fur microscopisch Anatomic und Ent- wickiungsmach 1876; 12:665. 3. Danforth CH. Hair with special reference to hypertrichosis. AMA Arch Dermatol Syphil 1925; 11:494. 4. Pinkus H. Embryology of hair. In: Montagna W, Ellis RA, eds. The Biology of Hair Growth. New York: Academic Press, 1958. 5. Sengel P. Morphogenesis of Skin. Cambridge: Cambridge University Press, 1976. 6. Spearman RIC. Hair follicle development, cyclical changes and hair form. In: Jar- rett A, ed. The Hair Follicle. London: Academic Press, 1977:1268. 7. Rook A, Dawber R. Diseases of the Hair and Scalp. Oxford: Blackwell Scientific Publications, 1982:5-6. 8. Holbrook KA. Structure and function of the developing human skin. In: Goldsmith LE, ed. Physiology, Biochemistry and Molecular Biology of the Skin. 2d ed. Vol. 1. New York: Oxford University Press, 1991:63. 9. Breathnach AS. Embryology of human skin. J Invest Dermatol 1971; 57:133.10. Smack DP, Korge, James WD. Keratin and keratinization. J Am Acad Dermatol 1994; 30:85-102.11. Briggaman RA. Biochemical composition of the epidermal-dermal junction and other basement membranes. J Invest Dermatol 1982; 78:1.12. Jarret A, ed. The Physiology and Pathophysiology of the Skin. Vol. III. The Dermis and Dendrocytes. London: Academic Press, 1974.13. Smith LO, Holbrook KA, Byers PH. Structure of the dermal matrix during devel- opment and in the adult. J Invest Dermatol 1982; 79:93S-104S.14. Halprin KM. Cyclic nucleotides and epidermal cell proliferation. J Invest Derma- tol 1979; 73:180-183.15. Bornstein P, Sage H. Structurally distinct collagen types. Ann Rev Biochem 1980; 49:957-1003.16. Mercer EH. Keratin and Keratinisation. Oxford: Pergamon, 1961.17. Barry BW. Dermatological Formulations: Percutaneous Absorption. New York and Basel: Marcel Dekker, 1983.18. Wertz PW, Downing DT, Glycolipids in mammalian epidermis: structure and func- tion in the water barrier. Science 1982; 4566:126.19. Elias PM. Epidermal lipids, barrier function, and desquamation, J Invest Dermatol 1983; 80:44S.20. Menon GK, Feingold KR, Elias PM. Lamellar body secretory response to barrier disruption. J Invest Dermatol 1992; 98:270.21. Elias PM. Lipids and the epidermal permeability barrier. Arch Dermatol Res 1981; 270:95-117.22. Holleran WM, Man MO, Wen NG, Gopinathan KM, Elias PM, Feingold KR. Sphingolipids are required for mammalian epidermal barrier function. J Clin In- vest 1991; 88:1338-1345.

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Biology of the Hair and Skin 3365. Elias PM. Epidermal lipids, barrier function, and desquamation. J Invest Dermatol 1983; 80:44s-49s.66. Jass HE, Elias PM. The living stratum corneum: implications for cosmetic formu- lation. Cosmet Toilet 1991 (Oct.); 106:47-53.67. HoUeran W, Feingold K, Man MO, Gao W, Lee J, Elias PM. Regulation of epi- dermal sphingolipid synthesis by permeability barrier function. J Lipid Res 1991; 32:1151-1158.68. Baker CG. Moisturization: new methods to support time proven ingredients. Cos- met Toilet 1987 (Apr.); 102:99-102.69. De Groot AC, Weyland JW, Nater JP. Unwanted Effects of Cosmetics and Drugs Used in Dermatology. 3d ed. Amsterdam: Elsevier, 1994:498-500.70. Friberg SE, Ma Z. Stratum corneum lipids, petrolatum and white oils. Cosmet Toilet 1993 (July); 107:55-59.71. Grubauer G, Feingold KR, Elias PM. Relationship of epidermal lipogenesis to cutaneous barrier function. J Lipid Res 1987; 28:746-752.72. Ghadially R, Halkier-Sorensen L, Elias PM. Effects of petrolatum on stratum cor- neum structure and function. J Am Acad Dermatol 1992; 26:387-396.73. De Groot AC, Weyland JW, Nater JP. Unwanted Effects of Cosmetics and Drugs Used in Dermatology. 3d ed. Amsterdam; Elsevier, 1994:498-500.74. Spencer TS. Dry skin and skin moisturizers. Clin Dermatol 1988; 6:24-28.75. Rieger MM, Deem DE. Skin moisturizers. II. The effects of cosmetic ingredients on human stratum corneum. J Soc Cosmet Chem 1974; 25:253-262.76. Robbins CR, Fernee KM. Some observations on the swelling of human epidermal membrane. J Soc Cosmet Chem 1983; 37:21-34.77. Idson B. Dry skin: moisturizing and Emolliency. Cosmet Toilet 1992 (July); 107: 69-78.78. Wehr RF, Krochmal L. Considerations in selecting a moisturizer, Cutis 1987; 39; 512-515.79. Brand HM, Brand-Garnys EE. Practical applciation of quantitative emolliency. Cosmet Toilet 1992 (July); 107:93-99.80. Goldemberg RL. Hair conditioners: the rationale for modern formulations. In: Frost P, Horwitz SN, eds. Principles of Cosmetics for the Dermatologist. St. Louis: Mosby, 1982:157-159.81. Garcia ML, Epps JA, Yare RS, Hunter LD. Normal cuticle-wear patterns in hu- man hair. J Soc Cosmet Chem 1978; 29:155-175.82. Zviak C, Bouillon C. Hair treatment and hair care products. In: Zviak C, ed. New York: Marcel Dekker, 1986:115-116.83. Rook A. The clinical importance of \"weathering\" in human hair. Br J Dermatol 1976;95:111-112.84. Robinson VNE. A study of damaged hair. J Soc Cosmet Chem 1976; 27:155-161.85. Finkelstein P. Hair conditioners. Cutis 1970; 6:543-544.86. Idson B, Lee W. Update on hair conditioner ingredients. Cosmet Toilet 1983 (Oct.); 98:41-46.87. Fox C. An introduction to the formulation of shampoos. Cosmet Toilet 1988 (Mar.); 103:25-58.88. Spoor HJ, Londo SD. Hair processing and conditioning. Cutis 1974; 14:689-694,

34 Draelos89. Arnoud R, Perbet G, Deflandre A, Lang G. ESR study of hair and melanin keratin mixtures: the effects of temperature and light. Int J Cosmet Sci 1984; 6:71-83.90. Jackowicz J. Hair damage and attempts to its repair. J Soc Cosmet Chem 1987; 38:263-286.91. Holt LA, Milligan B. The formation of carbonyl groups during irradiation of wool and its relevance to photoyellowing. Textile Res J 1977; 47:620-624.92. Launer HF. Effect of light upon wool. IV. Bleaching and yellowing by sunlight. Textile Res J 1965; 35:395-400.93. Inglis AS, Lennox FG. Wool yellowing. IV. Changes in amino acid composition due to irradiation. Textile Res J 1963; 33:431-435.94. Tolgyesi E. Weathering of the hair. Cosmet Toilet 1983 (Mar.); 98:29-33.95. Milligan B, Tucker DJ. Studies on wool yellowing. Part III. Sunlight yellowing. Textile Res J 1962; 32:634.

3The Role of Biological Lipids inSkin ConditioningPeter M. EliasUniversity of California, San Francisco, and Veterans Affairs Medical Center,San Francisco, CaliforniaI. EVOLVING CONCEPTS OF THE STRATUM CORNEUM BARRIERA. The Two-Compartment Model of the Stratum CorneumBecause of its loosely organized appearance in tissues subjected to routinefixation, dehydration, and embedding, the stratum corneum was not consid-ered to be important for normal permeability barrier formation until about 35years ago. However, when epidermis is frozen-sectioned and the cornified en-velopes of corneocytes are either swollen at alkaline pH or stained with fluo-rescent, lipophilic dyes, the stratum corneum appears as a compact structurewith geometric, polyhedral squames arranged in vertical columns that inter-digitate at their lateral margins (1,2). (Corneocytes are hardened cells viewedas closely packed bundles of keratin filaments.) Moreover, isolated sheets ofstratum corneum possess both unusually great tensile strength and very lowrates of water permeability (3). Hence, about 30 years ago the homogeneousfilm or \"plastic wrap\" concept of the stratum corneum emerged (4). However,since 1975 the stratum corneum has been recognized as comprising a struc-turally heterogeneous, two-compartment system, with lipid-depleting corneo-cytes embedded in a lipid-enriched, membraneous extracellular matrix. Morerecently, the stratum corneum has come to be appreciated as a dynamic andmetabolically interactive tissue. 35

36 Ellas1. Evidence for Intercellular Lipid SequestrationThe stratum corneum is viewed currently as a layer of protein-enriched cor-neocytes embedded in a lipid-enriched, intercellular matrix (5), the so-calledbricks-and-mortar model (6). The evidence for such protein-lipid sequestra-tion is based on freeze-fracture replication, histochemical, biochemical, cellfractionation, cell separation, and physical (4) chemical studies (reviewed inRef. 6). Freeze-fracture reveals stacks of intercellular bilayers in the intercel-lular spaces, where transmission electron microscopy previously had revealedonly empty spaces. Moreover, histochemical stains also display the membranedomains of the stratum corneum as enriched in neutral lipids, but only whenthese stains are applied to frozen sections. Furthermore, analysis of isolatedperipheral membrane domains showed directly that: (a) the bulk of stratumcorneum lipids are in the stratum corneum interstices; (b) the lipid compo-sition of these preparations is virtually identical to that of whole stratumcorneum; (c) the freeze-fracture pattern of membrane multilayers, previouslydescribed in whole stratum corneum, is duplicated in the membrane prepara-tions. Finally, X-ray diffraction and electron-spin resonance studies also local-ized all of the bilayer structures, as well as physiological, lipid-based thermalphenomena, to these membrane domains (7). The two-compartment model also explains the ability of cells in the outerstratum corneum to take up water (i.e., the lipid-enriched lamellar bilayers actas semipermeable membranes). However, the two-compartment, lipid-versus-protein model also requires updating based on recent evidence for microhet-erogeneity in these domains, e.g., the presence of extracellular proteins, suchas desmosomal components, and abundant enzymatic activity within the inter-cellular spaces.2. Cellular Basis for Lipld-Protein SequestrationSince its earliest descriptions (reviewed in Ref. 7), hypotheses have aboundedabout the function of the epidermal lamellar body. These ellipsoidal organ-elles, measuring about 1/3 *1/2 micro m, appear initially in the first supra basal celllayer, the stratum spinosum, and continue to accumulate in the stratum granu-losum, accounting for about 10% of the volume of the granular cell cytosol. Inthe outer granular layer, lamellar bodies move to the lateral and apicalsurfaces, where they are poised to undergo rapid exocytosis (8,9). The la-mellar body contains parallel membrane stacks enclosed by a limiting trilami-nar membrane. Whereas each lamella appears to be a \"disk\" in cross sections,with a major electron-dense band separated by electron-lucent material di-vided centrally by a minor electron-dense band, recent studies have showninstead that lamellar body contents comprise a single membrane structurefolded in an accordion-like fashion.

Biological Lipids and Skin Conditioning 37 To date, the factors, that regulate lamellar body secretion are not known.Acute perturbations of the barrier result in lamellar body secretion from theoutermost granular cell, accompanied by a striking paucity of these organellesin the cytosol (10). By 1-2 hr, abundant nascent lamellar bodies appear in thecytosol. Low rates of secretion apparently occur under basal conditions, whileboth organellogenesis and secretion are accelerated under stimulated condi-tions. Whether separate factors regulate the processes of basal versus stimu-lated secretion, as in other epithelia, is unknown. Cytochemists provided the first clues about the contents, and therefore thepotential functions, of this organelle (11,12). They found lamellar bodies to beenriched in sugars and lipids, thereby generating the initial hypothesis thattheir contents might be important for epidermal cohesion and waterproofing.Tracer perfusion studies initially demonstrated the role of the lamellar bodysecretory process in the formation of the barrier. Indeed, the outward egressof water-soluble tracers through the epidermis is blocked at sites where se-creted lamellar body contents have been deposited, and no other membranespecializations, such as tight junctions, are present at these locations to ac-count for barrier formation (13). Biochemical studies further support a role for organelle contents in barrierformation (14-16). Partially purified lamellar body preparations are enrichedin glucosylceramides, free sterols, and phospholipids, species which accountfor almost all of the stratum corneum intercellular lipids. They do not, how-ever, appear to be enriched in cholesterol sulfate, which may reach the inter-cellular spaces by an alternative mechanism. Moreover, degradation of theplasma membrane during terminal differentiation could result in in-situ deliv-ery of additional lipids to the pool of lipids already available for formation ofintercellular bilayers, and/or for the formation of the covalently bound enve-lope of the stratum corneum (see below). In addition to lipids, the lamellar body is enriched in certain hydrolyticenzymes, including acid phosphatase, certain proteases, a family of lipases,and a family of glycosidases (reviewed in Ref. 6). As a result of its enzymecontent, the lamellar body has been considered a type of lysosome, but evi-dence for this concept is lacking. Moreover, lamellar bodies lack certain acidhydrolases characteristic of lysosomes, such as arylsulfatases A and B and beta-glucuronidase (17). The same enzymes that are concentrated in lamellar bod-ies occur in high specific activity in whole stratum corneum, and are furtherlocalized specifically to intercellular domains both biochemically and cytochemi-cally (18). As will be discussed below, the enzymes present in lamellar bodiesmay fulfill dual roles in both barrier formation and desquamation (19-21). Theco-localization of \"pro-barrier\" lipids and various lipases (phospholipase A,sphingomyelinase, steroid sulfatase, acid lipase, and glucosidases) to the sametissue compartment appears to mediate the changes in lipid composition and

38 Ellasstructure that occur during transit through the stratum corneum interstices(22,23). Whereas the function of lamellar body-derived proteases in the cellu-lar interstices has not been investigated, they could either activate lamellarbody-derived hydrolases by conversion of pro-enzymes to active forms of theenzymes, and/or be involved in desmosomal degradation (see below). Steroid sulfatase, the enzyme responsible for desulfation of cholesterol sul-fate, is not enriched in isolated lamellar body preparations, yet somehow, thismicrosomal enzyme (7) reaches membrane domains in the stratum corneum(24). It is possible that the enzyme is present in lamellar bodies, but that it islost or destroyed during organelle isolation. However, it also is possible thatsteroid sulfatase may be transferred from microsomes to the limiting mem-brane of the lamellar body. Either process could result in either \"splicing\" ofenzyme into the corneocyte periphery or constitutive delivery to the extracel-lular spaces. An inadequately studied consequence of lamellar body secretion relates tochanges in: (a) the intercellular volume, and (b) the surface area:volume ratioof the stratum corneum and individual corneocytes resulting from coordinatedexocytosis of lamellar bodies. Preliminary studies suggest that the intercellularcompartment is greatly expanded (5-10% of total volume) (25) in comparisonto the volume of the interstices in other epithelia (1-2%). Moreover, thestratum corneum interstices serve as a selective \"sink\" for exogenous lipo-philic agents, which can further expand this compartment. Finally, althoughnot studied to date, the splicing of the limiting membranes of lamellar bodiesinto the plasma membrane of the granular cell results in an obligatory, massiveexpansion of the surface area:volume ratio of individual corneocytes, whichcould explain the remarkable water-holding capacity of corneocytes.B. Microheterogeneity of the Intercellular Spaces1. Lamellar Bilayer Generation, Maturation, and SubstructureLamellar body exocytosis delivers the precursors of these bilayers to the inter-cellular spaces at the stratum granulosum-stratum corneum interface (26). Atransition then can be seen from lamellar body-derived sheets into successivelyelongated membranes with the same substructure as lamellar body sheets,which unfurl parallel to the plasma membrane (27-29) (Figure 1). End-to-endfusion of lamellar body-derived membrane sheets continues within the firsttwo layers of the stratum corneum, giving rise to broad, uninterrupted mem-brane sheets, which is followed by compaction of adjacent membrane sheetsinto lamellar bilayer unit structures. This change in structure correlates witha sequence of changes in lipid composition, i.e., from the polar lipid-enrichedmixture of glycosphingolipids, phospholipids, and free sterols present inlamellar bodies to the more nonpolar mixture, enriched in ceramides, free

Biological Lipids and Skin Conditioning 39SG/SC INTERFACE LOWER TO MID SC 7.3 pH 5.0 Hydrated — > DehydratedFigure 1 Extracellular processing of polar lipids to nonpolar lipids is required forthe sequential membrane modifications that lead to barrier formation. In addition,changes in extracellular pH and hydration may contribute to this sequence.sterols, and free fatty acids, that is present in the remainder of the stratumcorneum (30). An explanation for the structural changes, consistent with thecompositional changes and enzyme localization data, is that the initial end-to-end fusion of unfurled lamellar body-derived sheets may be mediated by theinitial degradation of phospholipids to free fatty acids by phospholipase A2,which is present in abundance in lamellar bodies and the stratum corneuminterstices (Figure 1). The subsequent transformation of elongated disks intothe broad multilamellar membrane system required for barrier function is as-sociated with the further, complete hydrolysis of residual glucosylceramidesto ceramides. Until recently, elucidation of membrane structure in mammalian stratumcorneum was impeded by the extensive artifacts produced during processingfor light or electron microscopy (reviewed in Ref. 6). Following the applicationof freeze-fracture replication to the epidermis, the stratum corneum inter-stices were found to be replete with a multilamellar system of broad membranebilayers. Further detailed information about intercellular lamellar bilayerstructures has resulted from the recent application of ruthenium tetroxidepostfixation to the study of stratum corneum membrane structures (31-33).Despite its extreme toxicity to structural proteins, with ruthenium tetroxidepostfixation the electron-lucent lamella appears as pairs of continuous leafletsalternating with a single fenestrated lamella. Each electron-dense lamellais separated by an electron-dense structure of comparable width. The entiremultilamellar complex lies external to a hydrophobic envelope containing

40 Eliascovalently bound ceramides (see below). The lamellar spacing, or repeat dif-fraction, correlates extremely well with independent measurements of thesedomains by X-ray diffraction (34). Because the repeat distance is more than twice the thickness of typical lipidbilayers, each lamellar repeat unit appears to consist of two opposed bilayers.Multiples of these units (up to three) occur frequently in the stratum comeuminterstices, and simplifications of the basic unit structure, with deletion of oneor more lamellae, occur at the lateral surfaces of corneocytes, i.e., at three celljunctures (35). Dilatations of the electron-dense lamellae, which correspondto sites of desmosomal hydrolysis, also are visualized well with rutheniumstaining, and may comprise a \"pore pathway\" for percutaneous drug and xeno-biote movement. Correlation of images obtained with ruthenium tetroxide,biochemical methods. X-ray diffraction methods, and other physical-chemicalmethods (e.g., ESR and NMR) ultimately should provide an integrated modelof the architecture of the stratum comeum intercellular membrane system, aswell as important new insights about alterations in membrane structure re-sponsible for altered permeability states and pathological desquamation.2. Covalently Bound EnvelopeThe membrane complex immediately exterior to the cornified envelopereplaces the true plasma membrane during terminal differentiation (36). Al-though a portion of this trilaminar structure survives exhaustive solventextraction, it is destroyed by saponification (37). Lipid extracts of saponi-fied fractions yield at least two very long-chain, omega-hydroxy acid-contain-ing ceramides that are believed to be covalently attached to glutamine residuesin the cornified envelope (38). Although the covalently bound envelope isenriched in omega-hydroxy acid-containing ceramides, its complete composi-tion is not known, since both the initial solvent extraction of the intercellularlamellae and subsequent saponification could remove or destroy certain con-stituents of this structure. Since this envelope persists after prior solvent ex-traction has rendered the stratum corneum porous, it does not itself providea barrier. However, it may function as a scaffold for the deposition and organi-zation of lamellar body-derived, intercellular bilayers. Finally, the origin of thecovalently bound envelope remains unknown. It could originate from the poolof lipids deposited during lamellar body secretion, and/or by in-situ degrada-tion of plasma membrane sphingolipids, such as sphingomyelin.C. Extracellular Lipid ProcessingAs noted above, the sequestration of lipids within the intercellular spaces ofthe stratum corneum results from the secretion of the lipid-enriched contentsof lamellar bodies from the outermost granular cell. These organelles alsocontain selected hydrolytic enzymes which appear to regulate the formation

Biological Lipids and Skin Conditioning 41of a component permeability barrier as well as desquamation. Barrier forma-tion requires the transformation of the initially secreted lipids (predominantlyglucosylceramides, cholesterol, and phospholipids) into a more nonpolarmixture, enriched in ceramides, cholesterol, and free fatty acids. This proc-ess may require concomitant acidification of the extracellular domains (39).Such an acidic milieu may be required for optimal activation of certain of thekey hydrolases, beta-glucocerebrosidase, acid lipase, and sphingomyelinase.Whether epidermal extracellular phospholipases also display optimal activityat an acidic pH is unknown. Once activated, these enzymes generate the req-uisite nonpolar lipid mixture that forms the hydrophobic, intercellular lamel-lar bilayers (Figure 1). Proof of the role of intercellular beta-glucocerebrosidase in this processhas been provided by the use of both enzyme-specific inhibitors (conduritols)and a transgenic murine model (40,41). In both approaches, lack of enzymeactivity leads to a barrier abnormality, which appears to be attributable toaccumulation of glucosylceramides (not depletion of ceramides). This bio-chemical change is accompanied by the persistence throughout the stratumcorneum interstices of immature membrane structures. Interestingly, theseimmature or incompletely processed membrane structures also appear in asubgroup of Gaucher disease (type II), which is characterized by drasticallyreduced enzyme levels and ichthyosiform skin lesions (42). Such immature,glycosylated membrane structures, although inadequate to meet the demandsof terrestrial life, nevertheless appear to suffice in mucosal epithelia (43,44)and in the stratum corneum of marine cetaceans, which both display a highglycosylceramide-to-ceramide ratio (45). Pertinently, endogenous 13-glucosi-dase levels are reduced in oral mucosa (46). Thus, the persistence of glucosyl-ceramides may indicate less stringent barrier requirements in these localesand/or additional functions of glucosylceramides unique to these tissues. Extracellular processing of phospholipids also is required for barrierhomeostasis. As with beta-glucocerebrosidase, pharmacological inhibitors ofphospholipase A2 both delay barrier recovery after prior disruption (47) andinduce a barrier abnormality in intact murine epidermis (48). However, incontrast to beta-glucocerebrosidase, the biochemical abnormality responsiblefor the barrier defect is product depletion rather than substrate accumulation;i.e., co-applications of palmitic acid (but not linoleic acid) with the phospholi-pase inhibitors normalize barrier function. Thus, generation of nonessentialfree fatty acids by phospholipase-mediated degradation of phospholipids isrequired for barrier homeostasis. In summary, there is indisputable evidencethat activity of at least two stratum comeum extracellular enzymes is requiredfor barrier homeostasis. Whether extracellular processing of triglycerides,cholesterol esters, cholesterol sulfate, other acylglycerides, sphingomyelin,and/or glycerophospholipids (e.g., lysolecithin) by their respective hydrolases

42 Ellas(i.e., acid lipase, cholesterol ester hydrolase, steroid sulfatase, sphingomyeli-nase, phospholipase A1, and lysolecithinase) is (are) required for barrier ho-meostasis is unknown. Moreover, the role of active or passive acidificationmechanisms in triggering the extracellular processing of lipids in a sequentialor coincident fashion also remains to be explored.II. EPIDERMAL LIPIDSA. Role of Lipids in the Permeability BarrierThe importance of stratum corneum lipids for barrier integrity has been knownsince the old observation that topical applications of organic solvents produceprofound alterations in barrier function. More recently, the importance ofbulk stratum corneum lipids for the barrier has been demonstrated by: (a) theinverse relationship between the permeability of the stratum corneum to waterand water-soluble molecules at different skin sites (e.g., abdomen versus palmsand soles) and the lipid content of that site (49); (b) the observation that or-ganic solvent-induced perturbations in barrier function occur in direct propor-tion to the quantities of lipid removed (50); (c) the observation that stratumcorneum lipid content is defective in pathological states that are accompaniedby compromised barrier function, such as essential fatty acid deficiency (51,52); (d) the observation that replenishment of endogenous stratum corneumlipids, following removal by solvents or detergents, parallels the recovery ofbarrier function (53); and (e) that topically applied stratum corneum lipidsnormalize or accelerate barrier recovery when applied to solvent-treated,stripped, or surfactant-treated skin (54-56) (see below).B. Regional Variations In Human Stratum Corneum Lipid CompositionThe lipid composition of human stratum corneum lipids displays striking re-gional variations that could reflect differences in stratum corneum thickness,turnover, desquamation, and/or permeability. However, the barrier propertiesof these sites are not explicable by either site-related differences in thicknessor the number of cell layers in the stratum corneum. Instead, an inverse rela-tionship exists between the lipid weight percentage and the permeabilityproperties of a particular skin site (57,58). In addition to total lipid content,significant regional differences occur in the compositional profile of stratumcorneum lipids over different skin sites. For example, the proportion of sphin-golipids and cholesterol is much higher in palmoplantar stratum corneum thanon the extensor surfaces of the extremities, abdominal, or facial stratum cor-neum (59). However, the significance of these differences in lipid distribution

Biological Lipids and Skin Conditioning 43is not known, because the absolute quantities of each of these fractions isdependent on the lipid weight percentage of the stratum corneum at eachanatomical site. Thus, despite the high proportions of sphingolipids and cho-lesterol in palmar stratum corneum, when adjusted for the 2% lipid weight ofthis site, the absolute amounts of sphingolipids and cholesterol in the in-tercellular spaces are still much lower than in other, more lipid-enriched sites,Moreover, functional interpretations require consideration not only of lipiddistribution and weight percentages, but also information about site-relatedvariations in the fatty acid profiles of esterified species, and at present thesedata are not available. These regional differences in lipid content do have important clinical im-plications. First, they correlate with susceptibility to the development of con-tact dermatitis to lipophilic versus hydrophilic antigens at specific skin sites.Whereas allergy to a fat-soluble antigen, such as poison ivy (urushiol), is morelikely to occur in lipid-replete sites, allergy to water-soluble antigens, such asthose in foods, flowers, and vegetables, occurs more commonly on lipid-de-pleted sites; e.g., the palms. Second, subjects with atopic dermatitis, who dis-play a paucity of stratum corneum lipids, are less readily sensitized to lipid-soluble as opposed to hydrophilic antigens, such as nickel. Of course, the T-cellabnormalities in atopics also could contribute to differences in sensitizationthresholds. Third, percutaneous drug delivery of lipid-soluble drugs, such astopical steroids and retinoids, occurs more readily on lipid-replete sites, suchas the face—hence the relatively higher propensity to develop cutaneous sideeffects, such as steroid atrophy, at these sites. Conversely, lipid-soluble drugs,such as nitroglycerin, scopolamine, clonidine, fentanyl, and nicotine, are de-livered transdermally for systemic therapeutic purposes with relative ease overlipid-replete sites. Finally, the low lipid content of palms (and soles) explainsthe increased susceptibility of these sites to the development of soap/surfac-tant and hot water-induced dermatitis; i.e., these sites have a defective, lipid-deficient barrier prior to additional lipid removal, which superimposes a fur-ther insult. The distribution of lipids in nonkeratinized, oral mucosal sites, which gen-erally have a higher water permeability than keratinized regions, is differentfrom that in epidermis (60,61). Nonkeratinized regions, such as the buccalepithelia, contain no acylglucosylceramides and acylceramides and only verysmall amounts of ceramides. Glycosylceramides replace ceramides in nonk-eratinizing epithelia, apparently because of an absence of endogenous beta-glycosidase activity (62). Moreover, both keratinizing and nonkeratinizing re-gions of porcine oral epithelial contain more phospholipids than epidermis(63,64). Thus, the differences in permeability in epidermis versus mucosal epi-thelial may be explicable by the replacement of ceramides and free fatty acidsby glycosylceramides and phospholipids, respectively.

44 EllasC. Epidermal Lipid Synthesis1. Synthesis Under Basal ConditionsCutaneous lipid synthesis has been studied extensively both in vivo and in vitro(65,66). These studies have demonstrated, first, that the skin is a major site oflipid synthesis, accounting for 20-25% of total body synthesis (67,68), Second,the skin generates a broad range of lipid species (69). Third, about 70-75% ofcutaneous lipid synthesis localizes further to the dermis (70). The epidermis,which accounts for less than 10% of skin mass, accounts for 25-30% of totalcutaneous activity. Thus, the epidermis is an extremely active site of lipid syn-thesis, with about 60-70% of total lipid synthesis occurring in the basal layer(71). Considerable epidermal lipid synthesis, however, continues in all of thenucleated layers of the epidermis (72-74). It is now clear that systemic factorsinfluence cutaneous lipid synthesis minimally. Dramatic hormonal changes,particularly in thyroid, testosterone, or estrogen status, have been shown toalter epidermal lipid synthesis, but it is not clear that these hormones regulatecutaneous lipid synthesis under day-to-day conditions. In addition, changes incirculating sterols from either diet or drugs do not alter epidermal cholesterolsynthesis (75), presumably due to the paucity of low-density lipoprotein (LDL)receptors on epidermal cells (76-78). The autonomy of these layers from cir-culating influences may have evolutionary significance, because it ensures thatthe differentiating layers are attuned to their own, special functional require-ments, i.e., barrier homeostasis (see below). Despite its relative autonomyfrom the circulation, the epidermis incorporates some circulating lipids, suchas plant sterols, essential fatty acids, polyunsaturated fatty acids (PUFAs), andarachidonic acid (the epidermis lacks the 6-delta-desaturase). Although theselipids are indicators of the capacity of the epidermis to take up exogenouslipids, the quantitative contribution of extracutaneous lipids to the epidermalpool appears to be small in comparison to de novo synthesis (79).2. Metabolic Response to Barrier DisruptionDespite its relative autonomy and high basal rates of lipid synthesis, the epi-dermis responds with a further lipid biosynthetic burst when the permeabilitybarrier is disrupted by topical treatment with either organic solvents, tapestripping, or detergents (80,81). Regardless of the manner of barrier disrup-tion, a biphasic repair response occurs which leads to about 50% restorationof normal barrier function in about 12 hr in humans, with complete recoveryrequiring 72-96 hr (82). Quite different metabolic events are associated withthe rapid versus slow recovery phase. Immediately after barrier disruption, allof the lamellar bodies in the outermost granular cell are secreted (83), and aburst occurs in both cholesterol and fatty acid synthesis (84,85). In contrast,the late phase of barrier recovery is associated with a delayed burst in ceramide

Biological Lipids and Skin Conditioning 45synthesis (86), as well as a stimulation of epidermal DNA synthesis (87). Thatall of these alterations can be attributed to the barrier abnormality is shownby: (a) the localization of the increase in synthesis to the underlying epider-mis—dermal cholesterol and fatty acid synthetic rates remain unaffected afterbarrier disruption; (b) the extent of the increase in lipid and DNA synthesis isproportional to the degree of the barrier abnormality; (c) the burst in lipidsynthesis is prevented when the barrier is artificially restored by application ofwater vapor-impermeable (but not vapor-permeable) membranes, while theburst in DNA synthesis is partially blocked; and (d) in a sustained model ofbarrier dysfunction, i.e., rodent essential fatty acid deficiency, lipid synthesis isstimulated, and the increase is normalized when the barrier is restored by eitherlinoleic acid replenishment or occlusion (88). These results indicate that altera-tions in barrier function stimulate epidermal lipid synthesis, and suggest furtherthat transcutaneous water loss might be a direct or indirect regulatory factor. Although these results demonstrate that barrier function regulates epider-mal lipid synthesis, they do not address the basis for this metabolic response.Three of the most abundant lipid species in the stratum comeum are choles-terol, ceramides, and free fatty acids. The epidermal activities of the rate-limiting enzymes for these species, 3-hydroxy-3-methyl glutaryl coenzyme A(HMG CoA) reductase, serine palmitoyl transferase (SPT), acetyl CoAcarboxylase (ACC), and fatty acid synthase (FAS), is unusually high (89-91).Moreover, the activities of all these enzymes increase when the barrier is dis-rupted in both the acute and EFAD models. Whereas the changes in HMGCoA reductase, ACC, and FAS occur shortly after barrier abrogation, andreturn to normal quickly, the rise in SPT is more delayed and prolonged. Fur-thermore, the increase in activity of all these enzymes is blocked when thebarrier is restored artificially by occlusion with a vapor-impermeable mem-brane. Not only the total activity of the HMG CoA reductase, but the activa-tion state (phosphorylation state) of this enzyme, and perhaps ACC as well,are regulated by barrier requirements (SPT and FAS are not known to bephosphoiylated). Finally, the extent of the increase in the content and activa-tion state of HMG CoA reductase is proportional to the degree of barrierdisruption (92). Since the threshold for changes in the activation state of HMGCoA reductase changes with lesser perturbations in the barrier than thoserequired to increase enzyme content, reversible phosphorylation may allowboth rapid responses to barrier requirements and/or fine-tuning after minorinsults to the barrier. Finally, the changes in enzyme activity are preceded bychanges in the mRNA for at least two of these enzymes, HMG CoA reductase(93) and FAS (94). These data suggest that barrier requirements regulateepidermal lipid synthesis by modulating the content, activation state, andmRNA of the key regulatory enzymes of cholesterol, fatty acid, and sphingolipidsynthesis. Thus, acute change in the barrier initiate a sequence of events, in-

46 Ellaseluding rapid lamellar body secretion and increased lipid synthesis, which leadultimately to barrier restoration. Despite these specific increases in selected enzyme proteins and some non-enzyme proteins, such as beta-actin, bulk protein synthesis does not increase sig-nificantly after acute barrier perturbations. Moreover, applications of the pro-tein synthesis inhibitors, puromycin and cycloheximide, at doses which inhibitepidermal protein synthesis up to 50%, do not interfere with the kinetics ofbarrier repair (95). Thus, the stimulation of lipid and DNA synthesis repre-sents a selective, rather than a nonspecific consequence of barrier disruption.3. Requirements of Specific Lipids Versus Lipid Mixtures for Barrier FunctionWhereas metabolic studies clearly show that epidermal cholesterol, fatty acid,and ceramide synthesis are modulated by alterations in barrier function, thedemonstration that each of these lipids is required for the barrier requiresassessment of function after selective deletion of each of these species. Util-izing pharmacological inhibitors of their rate-limiting enzymes, each of thethree key lipids has been shown to be required for barrier homeostasis (96-98).Deletion of any of these species leads to abnormal barrier recovery and/orabnormal barrier homeostasis in intact skin. Having shown that each lipid is required individually, the next issue is whetherthey function cooperatively, i.e., whether they must be supplied together inproportions comparable to those present in the stratum comeum. Indeed, whencholesterol, free fatty acids, ceramides, or even acylceramides are applied aloneto solvent-perturbed skin, they aggravate rather than improve the barrier. like-wise, any two-component system of the three key stratum comeum lipids isdeleterious. In contrast, three-component mixtures of the key lipids, or two-component mixtures of acylceramides and cholesterol, allow normal barrierrecovery and can even accelerate barrier recovery, depending on the final pro-portion of the key lipids. The mechanism for the aggravation and ameliorationof barrier function by the physiological lipids is the same: they are quicklyabsorbed into the nucleated cell layers, and incorporated into nascent lamellarbodies. Whereas incomplete mixtures yield abnormal lamellar body contents,and disorder intercellular malellae, complete mixtures result in normal lamel-lar bodies and intercellular bilayers (99,100).III. POTENTIAL SIGNALS OF PERMEABILITY BARRIER HOMEOSTASISA. Ionic ModulationsThe ability of occlusion to block the lipid and DNA synthetic response to bar-rier disruption suggests that transepidermal water loss is a regulatory signal

Biological Lipids and Skin Conditioning 47for barrier homeostasis (101), yet a perturbed barrier recovers normally whenexposed to either isotonic, hypertonic, or hypotonic external solutions. In con-trast, if calcium, potassium, and to a lesser extent, magnesium and phosphorus,are present in the bathing solution, barrier recovery is impeded. Moreover,calcium and potassium together appear to be synergistic in inhibiting barrierrecovery. Since these inhibitory influences are reversed by blockade with in-hibitors of both L-type calcium channels and calmodulin, translocation of ex-tracellular calcium into the cytosol appears to be required (102). The mechanism for the negative ionic signal seems to relate to the presenceof a calcium gradient in the epidermis; with barrier disruption, the inhibitoryions are carried out passively into the stratum corneum (103,104). Moreover,it is depletion of calcium, rather than barrier disruption per se, that regulateslamellar body exocytosis, and perhaps lipid synthesis as well. Whether ionicsignals influence metabolic events in deeper layers of the epidermis, whereDNA synthesis and most of the lipid biosynthetic occur in response to barrierdisruption, is not known.B. Cytokine AlterationsWhereas the epidermis generates a large number of biological response modi-fiers (BRM) (105), the cytokine IL-a appears to be one of the few that ispresent in considerable quantities under basal conditions, where it accumulatesin the outer epidermis (106). In response to all forms of acute barrier disruption,a rapid increase occurs in the mRNA and protein content of several cytokines,including IL-a (107-111). Furthermore, the pre-formed pool of IL-a is re-leased from granular and comified cells, independent of new cytokine formation.Likewise, with sustained barrier disruption, as in essential fatty acid deficiency,both the mRNA and protein content of several of the cytokines increase. Whether these changes in cytokine expression represent in part a physi-ological response to barrier disruption versus a nonspecific injury responseremains unresolved. IL-a, TNF-a, and several other epidermis-derived BRMare potent mitogens (112), and both IL-a and TNF-a regulate lipid synthesisin extracutaneous tissues. Hence, it is tempting to regard these cytokineresponses as homeostatic. However, occlusion with a vapor-impermeablemembrane does not block the increase in either cytokine mRNA or proteinexpression after acute barrier abrogations (113). In contrast, sustained occlu-sion lowers cytokine mRNA and protein levels not only in essential fatty acid-deficient epidermis, but also in normal epidermis (114).C. Otiier Potential Signaling MechanismsIons and cytokines represent only two potential families of regulating signals.Among others to be considered, but not yet studied, are nitric oxide, various

48 EliasFigure 2 Contrasting outside-in versus inside-out views of triggering of commondermatoses, such as psoriasis and irritant contact dermatitis.keratinocyte-derived growth factors, neuropeptides, histamine, and eicosanoids.The epidermis synthesizes several potential regulators in these categories.Whether one or more of these will emerge as important regulators of barrierhomeostasis remains to be determined.IV. PATHOPHYSIOLOGICAL CONSEQUENCES OF BARRIER DISRUPTIONRecently, it has been suggested that diffusion into the dermis of one or moreof the cytokines or other BRMs generated during barrier abrogation, couldinitiate or propagate portions of the inflammatory response (115,116). Perti-nently, barrier disruption recently was shown to be followed by increased mi-gration of mitotically active Langerhans cells into the epidermis. Moreover,repeated barrier disruption leads to both epidermal hyperplasia and inflam-mation, changes which, again, are not presented by occlusion. This view pro-vides a relatively new outside--> inside concept, as opposed to the dominantinside-->outside view, of the pathogenesis of inflammatory skin diseases, suchas irritant contact dermatitis, psoriasis, and atopic dermatitis (Figure 2) (117,118).Thus, the leakage, diffusion, or escape of cytokines or other BRMs into thedermis following barrier disruption, could initiate dermal inflammation. Theseobservations have implications beyond the link between barrier functionand inflammation: they also provide a possible explanation for an additional groupof clinical skin diseases. For example, postinflammatory hyperpigmentation,regardless of specific cause, could be initiated by a barrier-initiated signalcascade (Figure 3). Moreover, if such varied insults as acute sunburn or exfoli-ative erythiodermas result in sufficient symptoms, fever and malaise can

Biological Lipids and Skin Conditioning 49 DERMISFigure 3 Related mechanisms, such as cytokines, may mediate both homeostatic(repair) and pathological sequences in the skin.result (Figure 3) (119). Finally, several additional signaling mechanisms canbe recruited during this process, further exacerbating the epidermal hyperpro-liferation and inflammation directly, and, if excessive, further exacerbating thebarrier abnormality. This vicious circle is likely to be operative in several im-portant dermatoses, such as psoriasis and a variety of eczemas.ACKNOWLEDGMENTSThis work was supported by NIH grant AR 19098 and the Medical ResearchService, Veterans Administration. Drs. Kenneth R. Feingold, GopinathanMenon, Erhardt Protsch, Simon Jackson, Nanna Schurer, Seung Lee, WalterHolleran, Man Mao Qiang, Karen Ottey, and many others contributed im-measurably to this research effort. Ms. Sue Allen and Mr. Jason Karpf capablyprepared the manuscript.REFERENCES 1. Feingold KR. The regulation and role of epidermal lipid synthesis. Adv Lipid Res 1991; 24:57-79.

50 Ellas 2. Elias PM, Feingold KR. Lipids and the epidermal water barrier: metabolism, regu- lation, and pathophysiology. Semin Dermatol 1992; 11:176-182. 3. Scheuplein RJ, Blank JF. Permeability of the skin. Physiol Rev 1971; 51:702-747. 4. Elias PM, Feingold KR. Lipids and the epidermal water barrier: metabolism, regu- lation, and pathophysiology. Semin Dermatol 1992; 11:176-182. 5. Elias PM, Friend DS. The permeability barrier in mammalian epidermis. J Cell Biol 1975; 65:180-191. 6. Elias PM. Epidermal lipids, barrier function, and desquamation. J Invest Dermatol 1983; 80:44-49. 7. Elias PM, Menon GK. Structural and lipid biochemical correlates of the epidermal permeability barrier. Adv Lipid Res 1991; 24:1-26. 8. Odland GP, Holbrook K. The lamellar granules of the epidermis. Curr Probl Der- matol 1987; 9:29-49. 9. Landmann L. The epidermal permeability barrier, Anat Ambryol 1988; 178:1-10.10. Ibid,11. Elias PM, Menon GK, Structural and lipid biochemical correlates of the epidermal permeability barrier. Adv Lipid Res 1991; 24:1-26.12. Odland GP, Holbrook K. The lamellar granules of the epidermis. Curr Probl Der- matol 1987; 9:29-49.13. Elias PM, Friend DS. The permeability barrier in mammalian epidermis. J Cell Biol 1975; 65:180-191.14. Menon GK, Feingold KR, Elias PM. The lamellar body secretory response to bar- rier disruption. J Invest Dermatol 1992; 98:279-289.15. Wertz PW, Downing DT, Freinkel RK, Traczyk TN. Sphingolipids of the stratum comeum and lamellar granules of fetal rat epidermis. J Invest Dermatol 1984; 83: 193-195,16. Grayson S, Johnson-Winegar AG, Wintroub BU, Isseroff RR, Epstein EH Jr, Elias PM. Lamellar body-enriched fractions from neonatal mice: preparative techniques and partial characterization. J Invest Dermatol 1985; 85:289-295.17. Ibid.18. Elias PM, Menon OK. Structural and lipid biochemical correlates of the epidermal permeability barrier. Adv Lipid Res 1991; 24:1-26.19. Ibid.20. Williams ML. Lipids in Normal and Pathological Desquamation. Adv Lipid Res 1991; 24:211-252.21. Menon GK, Williams ML, Ohadially R, Elias PM. Lamellar bodies as delivery systems of hydrolytic enzymes: implications for normal cohesion and abnormal desquamation. Br J Dermatol 1992; 126:337-345.22. Elias PM, Menon GK. Structural and lipid biochemical correlates of the epidermal permeability barrier, Adv Lipid Res 1991; 24:1-26.23. Fartasch M, Bassukas ID, Diepgen TH. Structural relationship between epidermal lipid lamellae, lamellar bodies and desmosomes in human epidermis: an ultras- tructural study, Br J Dermatol 1993; 128:1-9.24. Elias PM, Williams ML, Maloney ME, et al. Stratum comeum lipids in disorders of comification: steroid sulfatase and cholesterol sulfate in normal desquamation and the pathogenesis of recessive X-linked ichthyosis. J Clin Invest 1984; 74:1414-1421.

Biological Lipids and Skin Conditioning 5125. Menon GK, Price LF, Bommannan B, Elias PM, Feingold KR. Selective oblitera- tion of the epidermal calcium gradient leads to enhanced lamellar body secretion. J Invest Dermatol 1994; 102:789-795.26. Elias PM, Menon GK. Structural and lipid biochemical correlates of the epidermal permeability barrier. Adv Lipid Res 1991; 24:1-26.27. Landmann L. The epidermal permeability barrier. Anat Embryol 1988; 178:1-10.28. Menon GK, Feingold KR, Elias PM. The lamellar body secretory response to bar- rier disruption. J Invest Dermatol 1992; 98:279-289.29. Fartasch M, Bassukas ID, Diepgen TH. Structural relationship between epidermal lipid lamellae, lamellar bodies and desmosomes in human epidermis: an ultras- tructural study. Br J Dermatol 1993; 128:1-9.30. Elias PM, Menon GK. Structural and lipid biochemical correlates of the epidermal permeability barrier. Adv Lipid Res 1991; 24:1-26.31. Fartasch M, Bassukas ID, Diepgen TH. Structural relationship between epidermal lipid lamellae, lamellar bodies and desmosomes in human epidermis: an ultras- tructural study. Br J Dermatol 1993; 128:1-9.32. Madison KC, Swartzendruber DC, Wertz PW, Downing DT. Presence of intact intercellular lamellae in the upper layers of the stratum corneum. J Invest Derma- tol 1987; 88:714-718.33. Hou SYE, Mitra AK, White SH, Menon GK, Ghadially R, Elias PM. Membrane structures in normal and essential fatty acid deficient stratum corneum: charac- terization by ruthenium tetroxide staining and X-ray diffraction. J Invest Derma- tol 1991; 96:215-223.34. White SH, Mirejovsky D, King GI. Structure of lamellar lipid domains and cor- neocyte envelopes of murine stratum corneum, An X-ray diffraction study. Bio- chemistry 1988; 27:3725-3732.35. Hou SYE, Mitra AK, White SH, Menon GK, Ghadially R, Elias PM. Membrane structures in normal and essential fatty acid deficient stratum corneum: charac- terization by ruthenium tetroxide staining and X-ray diffraction. J Invest Dermatol 1991; 96:215-223.36. Elias PM, Menon G. Structural and lipid biochemical correlates of the epidermal permeability barrier. Adv Lipid Res 1991; 24:1-26.37. Swartzendruber DC, Wertz PW, Kitko DJ, Madison KC, Downing DT. Evidence that the corneocyte has a chemically-bound lipid envelope. J Invest Dermatol 1987; 88:709-713.38. Chang F, Swartzedrauber DC, Wertz PW, Squier CA. Covalently bound lipids in keratinizing epithelia. Biochim Biophys Acta 1993; 1150:98-102.39. Chapman SJ, Walsh A. Membrane-coating granules are acidic organelles which possess proton pumps. J Invest Dermatol 1989; 93:466-470.40. HoUeran WM, Takagi Y, Jackson SM, Tran HT, Feingold KR, Elias PM. Process- ing of epidermal glucosylceramides is required for optimal mammalian cutaneous permeability barrier function. J Clin Invest 1993; 91:1656-1664.41. HoUeran WM, Sidransky E, Menon GK, et al. Consequences of beta-glucocere- brosidase deficiency in epidermis: ultrastructure and permeability barrier altera- tions in Gaucher disease. J Clin Invest 1994; 93:1756-1764.42. Ibid.

52 Elias43. Wertz PW, Cox PS, Squier CA, Downing DT. Lipids of epidermis and kerati- nized and non-keratinized oral epithelia. Comp Biochem Physiol [B] 1986; 83: 529-531.44. Wertz PW, Kremer M, Squier SM. Comparison of lipids from epidermal and pala- tal stratum corneum. J Invest Dermatol 1992; 98:375-378.45. Elias PM, Menon GIC, Grayson S, Brown BE, Rehfeld SJ. Avian sebokeratocytes and marine mammal lipokeratinocytes: structural, lipid biochemical and func- tional considerations. Am J Anat 1987; 180:161-177.46. Chang F, Wertz PW, Squier CA. Comparison of glycosidase activities in epidermis, palatal epithelium, and buccal epithelium. Comp Biochem Physiol [B] 1991; 100: 137-139.47. Mao-Qiang M, Feingold KR, Jain M, Elias PM. Extracellular processing of phos- pholipids to free fatty acids is required for permeability barrier homeostasis. J Lipid Res. In press.48. Mao-Qiang M, Jain M, Feingold KR, Elias PM. Secretory phospholipase A2 activ- ity is required for permeability barrier homeostasis, J Invest Dermatol. In press.49. Lampe MA, Burlingame AL, Whitney J, et al. Human stratum corneum lipids: characterization and regional variations. J Lipid Res 1983; 24:120-150.50. Elias PM, Fritsch P, Epstein EH Jr. Staphylococcal scalded skin syndrome: clinical features, pathogenesis, and recent microbiological and biochemical developments. Arch Dermatol 1977; 113:207-219.51. Grubauer O, Feingold KR, Elias PM. Lipid content and lipid type as determinants of the epidermal permeability barrier. J Lipid Res 1989; 30:89-96.52. Elias PM, Brown BE. The mammalian cutaneous permeability barrier: defective barrier function in essential fatty acid deficiency correlates with abnormal inter- cellular lipid deposition. Lab Invest 1978; 39:574-583.53. Grubauer O, Elias PM, Feingold KR. Transepidermal water loss: the signal for recovery of barrier structure and function. J Lipid Res 1989; 30:323-333.54. Mao-Qiang M, Feingold KR, Elias PM. Exogenous lipids influence permeability barrier recovery in acetone treated murine skin. Arch Dermatol 1993; 129:728- 738.55. Mao-Qiang M, Brown BE, Wu S, Feingold KR, Elias PM. Exogenous non-physi- ological vs physiological lipids: divergent mechanisms for correction of permeabil- ity barrier dysfunction. Arch Dermatol. In press.56. Yang L, Elias PM, Feingold KR. Topical stratum corneum lipids accelerate barrier repair after tape stripping, solvent treatment, and some but not all types of deter- gent treatment. Br J Dermatol. In press.57. Lampe MA, Burlingame AL, Whitney J, et al. Human stratum corneum lipids: characterization and regional variations. J Lipid Res 1983; 24:120-150.58. Elias PM, Fritsch P, Epstein EH Jr. Staphylococcal scalded skin syndrome: clinical features, pathogenesis, and recent microbiological and biochemical developments. Arch Dermatol. 1977; 113:207-219.59. Lampe MA, Burlingame AL, Whitney J, et al. Human stratum corneum lipids: characterization and regional variations. J Lipid Res 1983; 24:120-150.60. Wertz PW, Cox PS, Squier CA, Downing DT. Lipids of epidermis and keratinized and non-keratinized oral epithelia. Comp Biochem Physiol [B] 1986; 83:529-531.

Biological Lipids and Skin Conditioning 536L Wertz PW, Kremer M, Squier SM. Comparison of lipids from epidermal and pala- tal stratum corneum. J Invest Dermatol 1992; 98:375-378.62. Chang F, Wertz PW, Squier CA. Comparison of glycosidase activities in epidermis, palatal epithelium, and buccal epithelium. Comp Biochem Physiol [B] 1991; 100: 137-139.63. Wertz PW, Cox PS, Squier CA, Downing DT. Lipids of epidermis and keratinized and non-keratinized oral epithelia. Comp Biochem Physiol [B] 1986; 83:529-531.64. Wertz PW, Kremer M, Squier SM. Comparison of lipids from epidermal and pala- tal stratum corneum. J Invest Dermatol 1992; 98:375-378.65. Yardley HI, Summerly R. Lipid composition and metabolism in normal and dis- eased epidermis. Pharmacol Ther 1981; 13:357-383.66. Ziboh VA, Chapkin RS. Metabolism and function of skin lipids. Prog Lipid Res 1988; 27:81-105.67. Turley SD, Anderson JM, Dietschy JM. Rates of sterol synthesis and uptake in the major organs of the rat in vivo. J Lipid Res 1981; 22:551-569.68. Feingold KR, Wiley MH, Moser AR, et al. De novo sterologenesis in the intact primate. J Lab Clin Med 1982; 100:405-410.69. Nicolaides N. Skin lipids. Science 1974; 186:19-26.70. Feingold KR, Brown BE, Lear SR, Moser AH, Elias PM. Localization of de novo sterologenesis in mammalian skin. J Invest Dermatol 1983; 81:365-369.71. Monger DJ, Williams ML, Feingold KR, Brown BE, Elias PM. Localization of sites of lipid biosynthesis in mammalian epidermis. J Lipid Res 1988; 29:603-612.72. Monger DJ, Williams ML, Feingold KR, Brown BE, Elias PM. Localization of sites of lipid biosynthesis in mammalian epidermis. J Lipid Res 1988; 29:603- 612.73. Proksch E, Elias PM, Feingold KR. Localization and regulation of epidermal HMO CoA reductase activity by barrier requirements. Biochem Biophys Acta 1991; 1083:71-79.74. HoUeran WM, Gao WN, Feingold KR, Elias PM. Localization of epidermal sphin- golipid synthesis and serine paimitoyl transferase activity. Arch Dermatol Res 1995; 287:254-258.75. Wu-Pong S, Elias PM, Feingold KR. Influence of altered serum cholesterol levels and fasting on cutaneous cholesterol synthesis. J Invest Dermatol 1994; 102:799-802.76. Ponec M, Havekes L, Kempenaar J, Vermeer BJ. Cultured human skin fibroblasts and keratinocytes: differences in the regulation of cholesterol synthesis. J Invest Dermatol 1983; 81:125-130.77. Mommaas-Kienhuis AM, Grayson S, Wijsman MC, Vermeer BJ, Elias PM. LDL receptor expression on keratinocytes in normal and psoriatic epidermis. J Invest Dermatol 1987; 89:513-517.78. Williams ML, Rutherford SL, Mommaas-Kienhuis AM, Grayson S, Vermeer BJ, Elias PM. Free sterol metabolism and low density lipoprotein receptor expression as differentiation markers in cultured human keratinocytes. J Cell Physiol 1987; 13332:428-440.79. Feingold KR. The regulation and role of epidermal lipid synthesis. Adv Lipid Res 1991; 24:57-79.80. Ibid.

54 Ellas81. Elias PM, Feingold KR. Lipids and the epidermal water barrier: metabolism, regu- lation, and pathophysiology. Semin Dermatol 1992; 11:176-182.82. Grabauer O, Elias PM, Feingold KR. Transepidermal water loss: the signal for recovery of barrier structure and function. J Lipid Res 1989; 30:323-333.83. Menon GK, Feingold KR, Elias PM. The lamellar body secretory response to bar- rier disruption. J Invest Dermatol 1992; 98:279-289.84. Menon OK, Feingold KR, Moser AH, Brown BE, Elias PM. De novo sterologene- sis in the skin. IL Regulation by cutaneous barrier requirements. J Lipid Res 1985; 26:418-427.85. Grubauer O, Feingold KR, Elias PM. Relationship of epidermal lipogenesis to cutaneous barrier function. J Lipid Res 1987; 28:746-752.86. HoUeran WM, Feingold KR, Mao-Qiang M, Gao WN, Lee JM, Elias PM. Regu- lation of epidermal sphingolipid synthesis by barrier requirements. J Lipid Res 1991; 32:1151-1158.87. Proksch E, Feingold KR, Mao-Qiang M, Elias PM. Barrier function regulates epi- dermal DNA synthesis. J Clin Invest 1991; 87:1668-1673.88. Feingold KR, Brown BE, Lear SR, Moser AH, Elias PM. Effect of essential fatty acid deficiency on cutaneous sterol synthesis. J Invest Dermatol 1986; 87:588-591.89. HoUeran WM, Feingold KR, Mao-Qiang M, Gao WN, Lee JM, Elias PM. Regu- lation of epidermal sphingolipid synthesis by barrier requirements. J Lipid Res 1991;32:1151-1158.90. Proksch E, Elias PM, Feingold KR. Regulation of 3-hydroxy-3-methyl-glutaryl-co- enzyme A reductase activity in murine epidermis: modulation of enzyme content and activation state by barrier requirements. J Clin Invest 1990; 85:874-882.91. Ottey K, Wood LC, Elias PM, Feingold KR. Cutaneous permeability barrier dis- ruption increases fatty acid synthetic enzyme activity in the epidermis of hairless mice. J Invest Dermatol 1995; 104:401-405.92. Proksch E, Elias PM, Feingold KR. Regulation of 3-hydroxy-3-methyl-glutaryl-co- enzyme A reductase activity in murine epidermis: modulation of enzyme content and activation state by barrier requirements. J Clin Invest 1990; 85:874-882.93. Jackson SM, Wood LC, Lauer S, et al. Effect of cutaneous permeability barrier disruption on HMG CoA reductase, LDL receptor and apoprotein E mRNA levels in the epidermis of hairless mice, J Lipid Res 1992; 33:1307-1314.94. Ottey K, Wood LC, Elias PM, Feingold KR. Cutaneous permeability barrier dis- ruption increases fatty acid synthetic enzyme activity in the epidermis of hairless mice. J Invest Dermatol 1995; 104:401-405.95. Choi S-J, Jackson SM, Elias PM, Feingold KR. The role of protein synthesis in permeability barrier homeostasis. In: Olikawara A, et al., eds, The Biology of the Epidermis: Molecular and Functional Aspects. Amsterdam: Elsevier, 1992:11-19.96. HoUeran WM, Mao-Qiang M, Gao WN, Menon OK, Elias PM, Feingold KR, Sphingolipids are required for mammalian barrier function: II. Inhibition of sphin- golipid synthesis delays barrier recovery after acute perturbation. J Clin Invest 1991; 88:1338-1345.97. Feingold KR, Mao-Qiang M, Menon OK, Cho SS, Brown BE, Elias PM. Choles- terol synthesis is required for cutaneous barrier function in mice. J Clin Invest 1990; 86:1738-1745.

Biological Lipids and Skin Conditioning 55 98. Mao-Qiang M, Elias PM, Feingold KR. Fatty acids are required for epidermal permeability barrier function. J Clin Invest 1993; 92:791-798. 99. Mao-Qiang M, Brown BE, Wu S, Feingold KR, Elias PM. Exogenous non-physi- ological vs physiological lipids: divergent mechanisms for corection of permeabil- ity barrier dysfunction. Arch Dermatol. In press.100. Mao-Qiang M, Feingold KR, Elias PM. Exogenous lipids influence permeability bar- rier recovery in acetone treated murine skin. Arch Dermatol 1993; 129:728-738.101. Grubauer O, Elias PM, Feingold KR. Transepidermal water loss: the signal for recovery of barrier structure and function. J Lipid Res 1989; 30:323-333.102. Lee SH, Elias PM, Proksch E, Menon GK, Mao-Qiang M, Feingold KR. Calcium and potassium are important regulators of barrier homeostasis in murine epider- mis. J Clin Invest 1992; 89:530-538.103. Menon GK, Lee S, Elias PM, Feingold KR. Localization of calcium in murine epidermis following disruption and repair of the permeability barrier. Cell Tissue Res 1992; 270:503-512.104. Menon GK,Ehas PM, Feingold KR.Integrityof the permeability barrier iscrucial for maintenance of the epidermal calcium gradient. Br J Dermatol 1994; 130: 139-147.105. Kupper TS. Immune and inflammatory processes in cutaneous tissues: mecha- nisms and speculations. J Clin Invest 1990; 86:1783.106. Hauser C, Saurat J-H, Schmitt JA, Jaunin F, Dayer JH. Interleukin-I is present in normal human epidermis. J Immunol 1986; 136:3317-3322.107. Wood LC, Jackson SM, Elias PM, Orunfeld C, Feingold KR. Cutaneous barrier perturbation stimulates cytokine production in the epidermis of mice. J Clin In- vest 1992; 90:482-487.108. Tsai JC, Feingold KR, Crumrine D, Wood LC, Grunfeld C, Elias PM. Perme- ability barrier disruption alters the localization and expression of TNF-alpha pro- tein in the epidermis, Arch Derm Res 1994; 286:242-248.109. Wood LC, Feingold KR, Sequeira-Martin SM, Elias PM, Orunfeld C. Barrier function coordinately regulates epidermal IL-1 mRNA levels. Exp Dermatol 1994; 3:56-60.110. Nicholoff BJ, Naider Y. Perturbation of epidermal barrier function correlates with initiation of cytokine cascade in human skin, J Am Acad Dermatol 1994; 30:535-546,111. Elias PM, Holleran WM, Feingold KR, Menon OK, Ohadially R, Williams ML, Normal mechanisms and pathophysiology of epidermal permeability barrier ho- meostasis. Curr Opin Dermatol 1993; 231-237.112. Kupper TS. Immune and inflammatory processes in cutaneous tissues: mecha- nisms and speculations. J Clin Invest 1990; 86:1783.113. Wood LC, Feingold KR, Sequeira-Martin SM, Elias PM, Orunfeld C. Barrier function coordinately regulates epidermal IL-1 mRNA levels. Exp Dermatol 1994; 3:56-60.114. Tsai J-C, Feingold KR, Crumrine D, Wood LC, Grunfeld C, Elias PM. Perme- ability barrier disruption alters the localization and expression of TNF-alpha pro- tein in the epidermis. Arch Derm Res 1994; 286:242-248.

56 Ellas115. Wood LC, Jackson SM, Elias PM, Orunfeld C, Feingold KR. Cutaneous barrier perturbation stimulates cytokine production in the epidermis of mice. J Clin In- vest 1992; 90:482-487.116. Nickoloff BJ, Naider Y. Perturbation of epidermal barrier function correlates with initiation of cytokine cascade in human skin. J Am Acad Dermatol 1994; 30:535-546.117. Scheuplein RJ, Blank IH. Permeability of the skin. Physiol Rev 1971; 51:702- 747.118. Ghadially R, Halkier-Sorenson L, Elias PM. Effects of petrolatum on stratum corneum structure and function. J Am Acad Dermatol 1992; 26:387-396.119. Kupper TS. Immune and inflammatory processes in cutaneous tissues: mecha- nisms and speculations. J Clin Invest 1990; 86:1783.

4Petrolatum: ConditioningThrough OcclusionDavid S. MorrisonPenreco, The Woodlands, TexasI. INTRODUCTIONSkin conditioning agents can be described as materials which improve the ap-pearance of dry or damaged skin. Many of these products are designed toremain on the skin for a length of time in order to reduce flaking and to act aslubricants. These conditioning agents help maintain the soft, smooth, flexiblenature of what is perceived as healthy, young-looking skin. Occlusive skin conditioning agents perform in such a manner that theevaporation of water from the skin surface (the stratum corneum) into theexternal environment is substantially blocked. This occlusivity helps to increasethe water content of the skin, giving it the desired supple appearance. Typi-cally, occlusive agents are lipids (molecules which are oil-soluble, and consistpredominantly of hydrogen and carbon atoms), which, due to their insolubilityin water, provide the best barrier to water vapor transport. The mechanism ofskin moisturization by these lipids is based on their tendency to remain on theskin's surface over time to provide a long-lasting occlusive film. Petrolatum (also called petroleum jelly and paraffin jelly) has been knownfor decades to be an excellent occlusive agent. Consisting of an extremely com-plex mixture of hydrocarbon molecules, it is obtained from the dewaxing ofrefined petroleum. This semisolid, unctuous material provides a substantialbarrier to moisture which is not easily breached, thus decreasing the loss ofwater from the skin to the environment (transepidermal water loss, or TEWL).This distinguishing attribute of petrolatum, coupled with its low cost, is the 57

58 Morrisonprimary reason why this material is a common ingredient in skin care products.Petrolatum requires no special handling or formulation considerations, andhas an excellent safety profile. These characteristics are evidenced by petrola-tum's continued use for decades as both a cosmetic ingredient and a finishedcosmetic product. When compared to the role of petrolatum in skin care, its position as a hairconditioner in the United States is more limited. Currently, much of its use inhair care products is directed toward the ethnic hair care market. Prior to the1960s and 1970s, the use of oil-based hair products was more frequent, as thesearticles were commonly utilized throughout the entire American population.Even today, anhydrous hair preparations are regularly used in other culturesaround the world. The primary purpose of using petrolatum in hair dressings,hair grooms, and other hair conditioning products is to hold the hair in placeand to add shine, neither of which can be easily (or inexpensively) obtainedwith any other single ingredient. Additional functions of petrolatum as a hairconditioner are to facilitate styling and to improve the texture of hair that hasbeen damaged by chemical and physical means (such as hair treated with high-pH relaxers). Outside the regular use of petrolatum in ethnic hair products(such as pomades, hair dressings, hair \"food,\" and brilliantines), this ingredi-ent is used in other hair care products, primarily emulsion styling creams andlotions, and anhydrous styling creams and gels. Although petrolatum has astrong tradition in the hair care market, water-based products using syntheticingredients as styling aids, hair-holding agents, and overall conditioners havegarnered a significant share of the consumer's spending on hair care. This hasbeen due mostly to fashion changes and, in more recent years, advancementsin polymer technology and in the synthesis of new functional personal careingredients for hair.II. PETROLATUM: ORIGIN AND HISTORYHaving been known for thousands of years, crude petroleum (crude oil) has avaried and extensive history (1-5). It is believed to have been found, whiledrilling for salt, by the Chinese, who used the material in ca. 1700 B.C. forlighting. Asphalt and other heavy, nonvolatile fractions of petroleum (such asbitumen and pitch) were used more often and in earlier times, since thesematerials do not evaporate with age as do the more volatile components ofpetroleum used in lighting and as fuels. These heavy materials are thought tohave been used as mortar and in other adhesive applications from before ca.2200 B.C. to at least the second century B.C. by the Assyrians and Babylonians.Not surprisingly, much of the archeological evidence of asphalt use has beendiscovered in the region of southern Mesopotamia (\"the cradle of civiliza-tion\") between the Tigris and Euphrates Rivers, as well as in ancient Persia.

Petrolatum: Conditioning Through Occlusion 59In addition to being employed for these purposes, asphalt was used around1000 B.C. by the Egyptians in some of their mummification procedures, as aprotective material and to fill body cavities. It also has been reported that the use of asphalt was proposed by the Assyri-ans for some undetermined medicinal purposes, and that certain lawbreakershad their heads \"anointed\" with the molten material! Since few people todaywould consider these applications as \"skin care,\" the date of the first knowncosmetic use of petroleum products is not very clear. It is known, however, thatcertain other ingredients were used to enhance beauty in Biblical times (suchas olive oil for hair preparations, and plant extracts and minerals for coloringpurposes) (6-9). In fact, several books of the Bible make reference to theancient custom of painting the eyelids and using mascara-like materials (suchas kohl) to highlight the eyes (10). By emphasizing their eyes in this manner,women made them appear larger and more attractive. Job, who was believedto have lived around 1845 B.C., had a daughter named Keren-Happuch, mean-ing \"container of eye paint,\" which also attests to the use of cosmetics duringthat time (11). The manufacture of petrolatum as a specific substance occurred only afterAugust 1859, when Edwin L. Drake drilled the first modern oil well (69 ftdeep) in Titusville, Pennsylvania. Prior to this time, significant quantities ofcrude oil had been obtained primarily from tar sands and other surface ornear-surface oil deposits. Petrolatum was probably first used as a cosmetic (i.e., skin care) ingredientin the several years preceding Robert A. Chesebrough's patent for petrolatum(12). In this patent, titled \"Improvement in Products from Petroleum,\" Chese-brough states that during the manufacture of petrolatum, the product's colorwill change over time from pure white to, eventually, a \"deep claret\" as thefilter material (\"bone black\") becomes more and more saturated. The petro-latum is described as a useful material for several leather treatment processes,and is \"a good lubricator, and may be used to great advantage on all kinds ofmachinery.\" In addition, Chesebrough remarks that the purest form of Vase-line (which he named this semisolid material) \"is also adapted to use as apomade for the hair, and will be found excellent for that purpose, one of itschief recommendations being that it does not oxidize.\" He then goes on tomention this substance's utility as a skin care treatment, citing, for example,its use on chapped hands. The name Chesebrough chose for the petrolatum which he manufactured[Vaseline (13)] apparently was derived from the German word for water(Wasser) and the Greek word for oil (14). The basis for this name was atheory mentioned by Chesebrough in an earlier U.S. patent. He believedthat Vaseline (i.e., petrolatum), consisting of carbon and hydrogen, wasformed by the combination of hydrogen (from the decomposition of water)

60 Morrisonand carbon (from certain minerals in the earth). Today, it has been wellestablished that petrolatum, and all the thousands, if not millions, of mo-lecular components of crude petroleum, have their origins not from water,but from organic materials which have decomposed naturally under the sur-face of the earth's crust. A significant body of scientific evidence points topetroleum as having been derived from once-living organisms (plant and ani-mal life), thus indicating that crude petroleum and its components are trulynatural materials. A short 2 years after Chesebrough's patent, a paper presented at the Phila-delphia College of Pharmacy reported that petrolatum showed some promiseas a pharmaceutical product and was \"certainly gaining favor with physicians\"(14). This was the beginning of petrolatum's use in pharmaceutical ointments,and the author of an 1875 paper published in the Proceedings of the AmericanPharmaceutical Association reported that this material was \"without a supe-rior\" and was most often used in the treatment of bums and scalds. Over 100years later, petrolatum still remains an extremely useful ingredient for similarmedical applications (vide infra). In 1880, petrolatum was first listed in theUnited States Pharmacopeia, indicating this material's wide acceptance as auseful pharmaceutical ingredient. One advantage of petrolatum cited by Chesebrough was its outstandingresistance to oxidation. Prior to Chesebrough's invention, lard (animal fat)and other unsaturated lipids were often used as ointments and salves. Thesematerials, not being preserved with antioxidants, quickly turned rancid, oftenleaving the user with a discolored, smelly product. At the February 2, 1876,meeting of the Pharmaceutical Society, one speaker stated that petrolatum\"may be kept indefinitely without becoming rancid, and this, together with itsindifference to chemicals and its readiness to take up any perfume, is sufficientto recommend it for pharmaceutical and toilet purposes in place of the fatsgenerally used\" (15). Thus, physicians and other medical practitioners readilyaccepted petrolatum as a great improvement over their currently used mate-rials. This natural immunity to oxidation is yet another characteristic of petro-latum which helps it retain its current popularity. In the late 1800s and early 1900s, most of the developments regarding pet-rolatum concerned its manufacture. Improvements were made in the dewax-ing of oils to yield the solid hydrocarbon residues for petrolatum production,and in the filtration of petrolatum. More recent advances in oil refining andmanufacturing have simplified the production of petrolatum, improved itsyield, and allowed more consistent products to be made. Even with currentimprovements, today's petrolatum has retained the natural characteristics ofthe original which Robert Chesebrough saw as being so valuable to hair andskin care. These timeless properties are what have kept this material as popu-lar as it is today.

Petrolatum: Conditioning Through Occlusion 61Table 1 Some Major Noncosmetic Applications of PetrolatumAgricultural chemicals MunitionsAluminum mills and containers Paint coatingsAnimal feed Paper applicationsAutomotive PharmaceuticalsBait Plastics industryCandles PolishesChemical processing Printing inkConcrete Rubber industryElectrical Rust preventativesFood processing SealantsIndustrial lubricants SoldersLeather processing TextilesModeling clay Veterinary applicationsIII. NONCOSMETIC USES OF PETROLATUMIn his patent on petrolatum, Chesebrough lists this material's use as a lubri-cant. While petrolatum is still used as a lubricant in certain industries, such asin aluminum mills and when manufacturing aluminum cans, it is used in amultitude of other products, processes, and industries. Table 1 lists many ofthe noncosmetic applications of petrolatum. In the agriculture industry, petrolatum is used as a fungicide carrier and infruit and vegetable coatings. These coating properties also allow it to be usedin rust-preventative compounds for food processing machinery and in auto-motive undercoatings. Its lubrication properties are useful in the automotive industry, especiallyduring reassembly of transmission parts. In the candle industry, petrolatum isused as a lubricant and also for aiding in the dissolution of fragrances, as wellas for minimizing wax shrinkage when clear jar candles are cooled. Petrola-tum's characteristics enable it to be used in textile manufacture, where it isemployed as a thread lubricant and in fiber finishes. Electrical applicationsbenefit from petrolatum, where it is used as a lubricant, insulation, and rustpreventative in electrical junction boxes. Petrolatum also can be used as afood-grade grease, as a rust preventative in food processing, and as a foodrelease agent. Its use in industrial applications is primarily in applicationswhere a remaining tacky film is desirable, such as in penetrating oils and ingasket lubricants and seals. Petrolatum's lubrication properties and its water-proofing abilities also are useful in the manufacture of munitions. Since minerals and other additives in animal feed are usually in powderform and have a tendency to dust and separate, petrolatum is used as a grain

62 Morrisondedusting agent and as a binder for pellets, cubes, and blocks in the processingof animal feed. It is also used in the manufacture of fishing lures and for woodimpregnation to aid in preservation. Marine base paints often contain petro-latum, as do water sealants, lacquers, and primers. Petrolatum has been usedfor decades as a concrete curing compound. It helps retain moisture in theconcrete during the curing process, which gives the final product its maximumcompressive strength, Petrolatum is useful in paper manufacture, specificallyfor the manufacture of butcher paper, carbon paper, and mimeograph forms. As cited by Chesebrough, petrolatum is useful in leather tanning (12). Here,petrolatum is used as an emollient to soften the hide and make it more pliable.Other leather applications include shoe polishes, leather conditioners for fin-ished leather goods, and in waterproofing compounds for boots. Besides sof-tening leather, petrolatum is used as a softener for modeling clay, while reduc-ing its drying time. Petrolatum is used as a plasticizer, as a mold release agentin plastic and rubber processing, and as an additive in printing ink solvents thatreduce tack. It also is used in solder flux. In the pharmaceutical industries, petrolatum is useful in dental adhesivesand in medicated ointments (both over-the-counter and prescription). It isused as a release agent for tablets and as a hospital lubricant for certain appli-cations. Petrolatum is used as a general protective salve in veterinary applica-tions, such as a lubricant for horses' leg shackles, and as cow udder ointment. The unique nature of petrolatum enables it to meet the requirements of theabove uses while still remaining a workhorse of the cosmetic industry. What isin this material that makes it so useful for many different applications?IV. THE COMPOSITION OF PETROLATUMDue to the chemical complexity of the constituents of crude oil and the vastnumber of different molecules in the refined fractions of petroleum, manydefinitions have been presented to describe the composition of petrolatum.This unctuous, semisolid material can be described as a complex, homoge-neous but colloidal mixture of solid and high-boiling liquid hydrocarbons,obtained from petroleum, which is transparent when spread in a thin layer.Petrolatums typically have melting points of between 35 and 60°C (dependingon the amount of solid hydrocarbon present), with molecular masses rangingfrom 450 to 1000. At these masses, classification of the components by mo-lecular type becomes extremely difficult due to the almost endless possibilitiesof substitution and isomers of the various molecules. In fact, even the simpli-fied nomenclature of petroleum components becomes blurred due to overlapbetween different species. The components in petrolatum can be generally classified as naphthenics,paraffinics, and isoparaffinics. The naphthenics are saturated ring structures

Petrolatum: Conditioning Through Occlusion 63(not aromatics), the paraffinics are straight-chain hydrocarbons, and the iso-paraffinics are branched-chain hydrocarbons. (Examples of these types ofmolecules are shown in Figure 1.) The difficulty in the discrimination of suchmolecules becomes evident when a ring structure contains several chains, bothstraight and branched. How is this molecule classified? Naphthenic becauseof the ring structure, paraffinic because of the straight chain, or isoparaffinicdue to the branched chain? In practice, when the naphthenic and paraffinicconstituents of a petroleum fraction are determined, one structure or anotherwill typically predominate, thus allowing a determination to be made. This isdone despite the inevitable fact that some molecules will always be in the \"grayarea\" between categories. Fortunately, understanding petrolatum and its keyproperties does not require the determination of its constituents to extrememolecular detail. Generally, the most practical knowledge of the composition of petrolatumis based on the amounts of solid and liquid components in the material. Thesolid components are obviously mineral waxes (e.g., paraffin and microciys-talline wax), while the liquid component is a heavy mineral oil. [It should benoted, however, that even this border between the solid wax hydrocarbons andliquid mineral hydrocarbons \"is neither definite nor scientific\" (16). One caneasily identify many saturated hydrocarbon molecules which melt at or nearambient temperatures.] The paraffin waxes are commonly recognized as par-affinic components, due to their brittleness. This lack of ductility arises fromthe ease by which the paraffinic molecules can align themselves and crystallize,due to the overall lack of significant branching. On the other hand, microcrys-talline waxes are isoparaffinic, will not crystallize easily due to molecularbranching, and so are not as brittle as the paraffin waxes. Despite understanding the oil and wax composition of petrolatum, it isknown that \"synthetic\" petrolatum cannot be created by simply combiningparaffin wax and mineral oil. When this is attempted, the blend does not re-main uniform and separates. Thus, it was believed at one time that a thirdsubstance was present which kept the wax-and-oil mixture stable. This materialwas named \"protosubstance\" by F. W. Breth, who claimed the discovery of thiscomponent in an unpublished study in 1925 (17). The \"protosubstance\" was obtained by repeatedly extracting petrolatumwith acetone, but no adequate explanation for how protosubstance works wasever found. In addition, no amount of the extracted protosubstance could con-vert a mixture of mineral oil and wax into petrolatum. Today, while there stillmay be some believers in the protosubstance theory, the general consensus isthat no substantial scientific evidence has been published which conclusivelyproves the existence of protosubstance and the requirement that it be presentfor petrolatum to exist. Therefore, claims to the presence of protosubstanceare usually met with skepticism.

64 Morrison Naphthenic Hydrocarbon Isoparaffinic Hydrocarbon Paraffinic HydrocarbonFigure 1 Examples of hydrocarbon types found in petrolatum.

Petrolatum: Conditioning Through Occlusion 65Figure 2 Microphotograph of petrolatum (l00x). Note the wax crystals.Figure 3 Microphotograph of petrolatum (500x). Wax crystals are dearly seen.

66 Morrison Although mineral oil and paraffin wax cannot be mixed to create petrola-tum, various types and grades of petrolatum can be prepared which containdiffering amounts of wax and oil. This allows numerous blends to be prepared,each designed to meet a specific need. Obviously, petrolatums with high levelsof wax have high melting points and hard consistencies, while those with moreoil are softer and more fluidlike. The waxes which are present in petrolatumare clearly evident when samples are viewed under a microscope. Figure 2shows a microphotograph (100 x) of a petrolatum, while Figure 3 is the samematerial photographed at 500 x. In both photos, the wax crystals can be seenquite easily. In order for petrolatum to be labeled \"Petrolatum, U.S.P.\" or \"White Pet-rolatum, U.S.P.,\" it must conform to the requirements described in the UnitedStates Pharmacopoeia. One of the tests it must meet is a consistency test. Sinceadding too much oil or too much wax to a petrolatum may cause the finalproduct to fail this U.S.P. requirement, care must be taken when blendingpetrolatums to ensure that the product's consistency does not fall outside therequired range if the final material is to be U.S.P. petrolatum. Note that theU.S.P. also has other requirements for petrolatums, but these are easily foundin the United States Pharmacopoeia and will not be discussed here, as they areoutside the scope of this chapter.V. REFINING AND PRODUCTIONAs stated previously, petrolatum is a purified, semisolid mixture of hydrocar-bons taken from petroleum (crude oil). Since petroleum is obtained from theearth, and since the materials it contains are simply refined (i.e., separatedfrom impurities) and not synthesized, petrolatum can be considered a naturalmaterial in the truest sense of the word (18). The exact method of production of petrolatum varies depending on severalfactors. These factors include the type of crude oil used (the chemical compo-sitions of crude oils from different sources vary considerably, as do the boilingrange and other physical properties which affect the conditions used to refinethe petroleum) and the types of petroleum products desired at the end of therefining process. However, a general process for the manufacture of petrola-tum, from crude oil to the final product, is described below. Figures 4,5, and 6 show the general scheme of a petroleum refinery process,with focus on the production of petrolatum. First, a crude oil is subjected toatmospheric distillation, which removes gases and lighter refined products(i.e., fuels, such as gasoline, kerosene, and Diesel fuel) from the bulk of thecrude oil product at atmospheric pressure. The remaining oil is sent to a vac-uum distillation unit so that the heavier fractions (e.g., lubricating oil fractions)can be removed without the extreme temperatures which would be required

Petrolatum: Conditioning Through Occlusion 67Figure 4 Petroleum refinery process No. 1.to perform this operation in an atmospheric distillation tower. Once these lubeoil fractions are removed, the remaining material, often called \"vacuum resid,\"is then taken to a solvent deasphalting/deresining unit. In this process, a sol-vent is used to extract the heavy oil from resins and asphalts which would bedetrimental components in the finished petroleum products. The deresined or deasphalted oil is purified further by one of two methods(Figure 5). It can be hydrotreated, which is simply a hydrogenation step toconvert unsaturated molecules to saturated ones and to remove heteroatomssuch as sulfur and nitrogen compounds. Another method is to extract these sameimpurities by mixing the oil with a suitable solvent. The more polar materialsDeresined/ WaxDeasphalted Product OilFigure 5 Petroleum refinery process No. 2.

*Blended with other components as needed to make various grades and types of petrolatum.Figure 6 Petroleum refinery process No. 3.(unsaturated and heteroatom compounds) will preferentially be dissolved inthe solvent, thus leaving behind an oil which is essentially free from unwantedcomponents. Following this process, the oil is treated in a dewaxing step. The dewaxing of oil can be done in one of two ways. When the goal of therefinery is to minimize production of waxes and wax-containing materials, acatalytic dewaxing process is used. In this case, the oil is treated with a metalcatalyst which causes the waxes to break apart into smaller molecules. De-pending on the size of these newly created molecules, they can be captured aspetroleum gases, fuels, or lubricating oils. This is an efficient method to maxi-mize the output of these materials. When petrolatum or waxes are to be produced, this step is a solvent dewax-ing, wherein the oil is heated and mixed with a hot solvent. The waxy materialfrom the oil will be dissolved in the solvent, which then is cooled and/or cen-trifuged to remove the waxes. The heavy oil which remains is essentially freeof waxes which could limit the oil's use as a lubricant. This oil is called brightstock and often is used as a component in high-viscosity oil products. The waxproduct yielded by this process is then further refined as shown in Figure 6. Depending on the desired properties of the final petrolatum material, thewax product obtained from the solvent dewaxing step can be blended withother components such as oils and other waxes. This wax product or wax prod-uct blend is hydrotreated once again to further remove unsaturation and het-eroatom compounds, followed by either bauxite filtration or a second hydro-treatment step to remove the ever-decreasing amounts of impurities. This willproduce a petrolatum which is pure enough to meet U.S.P. standards and issafe enough for direct use on human lips.

Petrolatum: Conditioning Through Occlusion 69 Different \"variations\" of petrolatum can be obtained (higher or lower melt-ing points, different consistencies, etc.) by changing the formula of the waxproduct which is to be purified, as shown in Figure 6. Another method ofpreparing different petrolatums involves simply blending the final petrolatumproduct with wax and/or oil. Since the petrolatum is already present as the basematerial, additional wax or oil can be mixed without the aforementioned prob-lems of separation which are encountered when attempts are made to preparepetrolatum from just oil and wax. Of course, in every step along this lengthy production process, the refineryoperator can make adjustments which will vary the types and amounts of prod-ucts formed. Thus, the process is quite flexible and allows the maximum utili-zation of crude oil while simultaneously providing maximum yield of the de-sired petroleum products. Such an efficient process enables the refinery tomake multiple salable products with essentially no waste. Given the cost ofcrude oil, it is not surprising that the petroleum refinery recycles the processingmaterial as much as possible and utilizes every drop of the crude oil.VI. APPLICATIONS OF PETROLATUMA. Skin Conditioning as a Cosmetic ingredientTwo key characteristics of many skin conditioning agents are that they elim-inate dry skin and maintain moist, healthy skin. Petrolatum is one ingredientwhich has performed these roles superbly for decades. In fact, the first publicdocument which described the benefits of petrolatum on dry skin was probablyChesebrough's 1872 patent (12), in which he cited its excellence for use onchapped hands. The current literature overflows with evidence that petrola-tum acts on the skin to make it more moist, supple, and both visually andphysiologically appealing. Even newspapers and magazines tout the benefitsof spreading petrolatum onto dry skin, especially during the winter seasonwhen the need for skin moisturizers is great due to a combination of low hu-midity, indoor heat, and reduced fluid intake. While some studies indicate possible pharmacological mechanisms involv-ing petrolatum and the skin, this material's excellent occlusivity is the primaryreason why it is used as a skin conditioner. Blank showed in 1952 that waterin the stratum corneum is a primary factor for supple, smooth, healthy-lookingskin (19); therefore, ingredients which are effective at keeping moisture in skin(such as petrolatum) will undoubtedly be excellent skin conditioners.1. General InformationThis conviction is widely held throughout the cosmetic industry. Petrolatum isknown as an excellent moisturizer, and this \"moisturization\" (i.e., reductionof transepidermal water loss, TEWL) of the skin by petrolatum arises from its

70 Morrisonocclusion. Thus, it is frequently found in many skin care formulations, espe-cially since liquid occlusive agents (e.g., lipophilic oils) are less effective mois-turizers than petrolatum (20). Hydration of the stratum corneum, such as thatprovided by petrolatum, may reach all strata of the skin under certain circum-stances, which clearly relates to a favorable skin physiology (21). Numerous authors have cited petrolatum's conditioning of the skin viaocclusivity. Steenbergen reported that petrolatum is the most efficient sub-stance for retaining moisture in the skin and allowing it to hydrate to the pointwhere the dry skin condition is overcome (22). A recent column by Fishman(23) stated that, for treating dry skin, petrolatum is a \"classic emollient\" andis \"extremely efficient\" at doing its job. White petrolatum was noted as beingthe best occlusive moisturizer in an article by Fisher and co-workers (24). Ad-ditionally, white petrolatum was recommended as the ideal moisturizer forpeople with abnormal skin, defined as that segment of the population withcosmetic dermatitis, since petrolatum is such a good moisturizer and it needsno preservative. An excellent paper on dry skin also has been published byIdson (25). In this fairly comprehensive article, the author reviews dry skin,the structure and function of skin, emolliency, and moisturization. Eventhough oils which contain fatty acid glycerides contribute to overall skinflexibility, Idson writes, their occlusion (and thus moisturization) falls far shortof that provided by petrolatum. The efficiency and superiority of petrolatumas a skin conditioning agent was once again referred to, as this material wascalled \"the most efficient occludent and emollient for protecting dry skin andallowing it to hydrate again.\" A chart in this paper placed petrolatum at thetop of a list of emollient preparations, based on the ability to \"protect\" dryskin. It should be noted that the ability of petrolatum to protect and moisturizedry skin also applies to lips. This occlusive substance is probably the mostcommonly used ingredient in lip balms, and in some instances, petrolatum isessentially the only ingredient. Chapped lips (i.e., \"dry skin\") are ideal sitesfor petrolatum application due to both its safety as well as its skin conditioningand moisturization. Petrolatum also was mentioned in an interview in a 1990 issue of Dermatol-ogy Times regarding nonprescription products for improving the appearanceof skin, hair, and nails (26). This article stated that traditional moisturizers areproducts which typically contain occlusive ingredients, such as petrolatum,which reduce water vapor loss from the skin.2. In-Vivo StudiesThese and other reports of skin-hydrating effects from the occlusivity of pet-rolatum have been proven in clinical trials using human subjects. These in-vivostudies conceivably give the best verification of the skin conditioning ability of

Petrolatum: Conditioning Through Occlusion 71petrolatum, since they are as close to \"real-world\" situations as are typicallyavailable. In 1978, Kligman published an article describing a regression method forevaluating moisturizers (27). This method, which has gained wide acceptance(28), was used to assess the efficacy of a number of moisturizers (both formu-lated products and ingredients). Not surprisingly, petrolatum was found to bethe best moisturizer, which was defined as \"a topically applied substance orproduct that overcomes the signs and symptoms of dry skin.\" The data Klig-man obtained from the evaluation of ingredients and finished products en-abled him to conclude the following: \"When it comes to efficacy, petrolatumis the unrivaled moisturizer. No material in our experience exceeds it in reliev-ing ordinary xerosis.\" Some of the materials used in this study were petrola-tum, mineral oil, olive oil, a commercial hand cream, and a commercial facecream. These were applied to dry skin once daily for 3 weeks. Lanolin also wasstudied and was applied twice daily for 3 weeks. The results, shown in Figure7, indicate that petrolatum is a superior moisturizer both at the end of treat-ment (3 weeks) and at 4 weeks (1 week beyond the end of treatment). Thepetrolatum gave the greatest decrease in xerosis grade (the greatest improve-ment in dry skin conditions) from pretreatment to the end of treatment, aswell as to 1 week after treatment had stopped. Thus, petrolatum was shown to3 Weeks (End of Treatment) 4 Weeks (One Week After Treatment)Figure 7 Approximate decrease in xerosis grade (from pretreatment grade) of vari-ous materials. A larger value means a greater improvement in xerosis (27).

72 Morrisonexhibit excellent relief for dry skin both during and after application of thematerial. Kligman also stated that the mode of action of petrolatum is not just occlu-sion of moisture from the skin, since wrapping the skin with an impermeableplastic film does not benefit dry skin. He theorized that petrolatum may havesome pharmacological effects which contribute to its role as a moisturizer, butthe mode of such action has not been determined. If such pharmacological effects do occur, they are likely confined to the skinsurface and stratum corneum. Elias and co-workers have shown that hydro-carbons such as petrolatum, when applied topically, do not penetrate to thedeeper layers of the skin (29). This holds true for both intact and acetone-damaged skin. When skin is damaged by acetone, it was found that petrolatum(applied topically) permeates all levels of the stratum corneum, implying that,in addition to moisturizing the skin, it helps repair the damaged tissue (30).The petrolatum actually increased the rate of healing the damaged skin,whereas a vapor-impermeable film impairs this process. Like Kligman, theseauthors concluded that petrolatum is not acting only as an inert, occlusivebarrier to skin moisture. In 1992, Loden published a study on the increase in skin hydration afterlipid-containing materials were applied (31). The materials tested were petro-latum, an oil-in-water cream containing an unusually high concentration oflipids (66%), and an oil-in-water cream containing 27% lipids. The occludingproperties of these materials were determined by application to skin, followedby determination of TEWL 40 min later. This author found that petrolatumreduced water loss from the skin by nearly 50%, whereas the other materialsreduced water loss by only 16% (Figure 8). While this result is expected basedon the well-known occlusivity of petrolatum, one of the most interesting as-pects of this study was the evaluation of TEWL following removal of the prod-ucts 40 min after application. In this case, petrolatum gave a very high TEWLrelative to the oil-in-water creams, indicating that the skin was hydrated bypetrolatum to a greater extent than by the creams. Not only was the occlusionof petrolatum determined, the direct hydration of the skin by this occlusionwas verified as well. In another study on the effectiveness of cosmetic products and their abilityto alleviate dry skin conditions, petrolatum was evaluated as an emulsifiedingredient. This emulsion was compared to other emulsions which containedeither urea or alpha-hydroxy acids (AHAs) (32). The panelists had their skinanalyzed over a 4-week period by \"expert assessors,\" who judged the severityof skin dryness visually. It was found that an emulsion containing 15% petro-latum was equivalent to a 10% urea emulsion in reducing dryness when meas-ured weekly over 4 weeks. A second 4-week study compared the 15% petro-latum emulsion with an emulsion containing 6% AHAs, and again, the two

Petrolatum: Conditioning Through Occlusion 73 Petrolatum Low-lipid Cream High-lipid CreamFigure 8 The effects of three emollients on TEWL (31).products were essentially identical in performance as determined by a reduc-tion in the visual characteristics of skin dryness. These results suggest that routesother than occlusion may be used to reduce the appearance of dry skin, but itis evident that the decades of proven safety and the economy of petrolatum wouldinvite formulators to select it over the urea and AHAs when developing anemulsion product designed primarily to eliminate or reduce dry skin. The occlusivity of \"oil films\" was the subject of a 1979 publication by Tsut¬sumi and co-workers, who compared three physical forms of hydrocarbons andtheir reductions in TEWL when applied to human skin (33). The hydrocarbonsthey studied were liquid (mineral oil), solid (paraffin wax, m.p. 48°C), andsemisolid (petrolatum). These authors found that for all three materials, in-creasing the amount of hydrocarbon applied to the skin increased the occlu-sivity as measured by a Servo Med evaporimeter, but the occlusivity eventuallyleveled off. While this finding is not unexpected, comparing all three materialsat the same concentration was especially telling. Figure 9 shows the results ofthis study when 1 mg of hydrocarbon was used per square centimeter of skin(applied as a solution in a volatile solvent) and TEWL (occlusivity) was measuredat 15 and 60 min after application. This figure indicates that petrolatum clearlyoutperformed the other materials. Although the solid paraffin hydrocarbonshowed very good occlusivity when applied uniformly, its tendency to crack(and thus lose its barrier properties) and overall poor esthetics do not lend it tocommon cosmetic use as a primary emollient/moisturizer/conditioning agent.

74 Morrison1009080706050 44030 -20-100 After 60 Minutes After 15 MinutesFigure 9 Barrier properties of three forms of hydrocarbon (33). 30 60 90 Time, minutes after applicationFigure 10 How rubbing petrolatum 90 min after application affects its occlusivity(33).

Petrolatum: Conditioning Through Occlusion 75 In a noteworthy sidelight to this study, the authors also reported on theeffect of rubbing petrolatum once it had been applied to the skin and leftundisturbed for a period of time. A sample of petrolatum was placed on theskin by simply spreading it into a film. The occlusivity of this film was measuredat 30,60, and 90 min after application. The occlusivity dropped from 89% (at30 min) to 58% (at 90 min). However, when this film was rubbed at 90 minafter application, the occlusivity increased to 84% (Figure 10)! What is occur-ring here? The authors suggest that the film of petrolatum may become dis-continuous over time. Another possibility is that the water vapor begins tocreate molecular scale \"channels.\" In either case, an increase in water vaporpermeation is taking place. Whatever the reason for this increase in vaporpermeation, rubbing the film restores occlusivity by creating a more solid, con-tinuous film, thus reducing the vapor transport across the petrolatum. A paper by Rietschel published in The Journal of Investigative Dermatologyin 1978 also reported on the in-vivo evaluation of skin moisturizers (34). Thisauthor determined that occlusion (such as with petrolatum) is an effectivemethod for treating dry skin, with or without hydration of the skin prior toapplication of the occluding material. The suppression of moisture loss fromthe skin was plainly seen in Rietschel's studies and is shown in Figure 11, takenfrom Rietschel's paper.Figure 11 The suppression of detectable moisture by petrolatum (0.02 mL petrola-tum applied to 6.25 cm2 of normal skin) attributed to occlusion. (Reprinted from Ref.34 with permission.)

76 MorrisonFigure 12 In-vivo moisturizing abilities of various lipid emollients as measured byTEWL (36). Petrolatum gives a greater reduction in TEWL than the other emollients. This occlusivity of petrolatum has been evaluated in other studies. For ex-ample, hairless rats have been used in an evaluation of the hydrating effectsof cosmetic preparations (including petrolatum) as measured by cutaneousimpedance (35). An initial increase in impedance is seen with petrolatum,which corresponds to this material's resistivity. This resistivity indicates thatthe petrolatum is highly impermeable to water, and the intensity and durationof this impedance increase was determined to be proportional to the amountof p>etrolatum used. FrOmder and Lippold have published a study of water vapor transmissionand occlusivity using both in-vivo and in-vitro techniques to evaluate lipidsoften used as ointment ingredients (36). White petrolatum was found to bethe best lipophilic excipient at reducing TEWL in vivo (Figure 12) and at pre-venting water vapor transmission in vitro when compared to mineral oil, di-methiconc, and several emollient esters (Figure 13).3. in-vitro StudiesThis often-cited reduction of water vapor permeation by petrolatum has beendetected by others using in-vitro studies. One particular article has praised the

Petrolatum: Conditioning Through Occlusion 77Figure 13 A study of in-vitro water vapor permeation (36). Notice that the nonpolarhydrocarbons (especially petrolatum) are significantly better at preventing water vaportransmission than dimethicone and the more polar esters.moisturizing properties of mineral oil and petrolatum based on such studies.Tranner and Berube, in 1978, reported the results from a test which measuredthe reduction of water loss by various materials across a nylon film used as askin substitute (37). The results from this screening test (performed at 20%relative humidity) are shown in Figure 14 and verify the superior ability ofpetrolatum to prevent skin water loss by acting as an occlusive vapor barrier. In a study on the effects of petrolatum, white mineral oil, and gelled whiteoils on stratum comeum lipids, Friberg and Ma showed that petrolatum isretained in the outer layer of skin (38). Using a liquid crystal model of thestratum comeum, these authors indicated that the petrolatum reaches all lev-els of the stratum comeum, but it is not incorporated in the layered lipid struc-ture of the skin. The strength of petrolatum as a skin moisturizer by acting asa barrier to vapor permeation also was noted. Another in-vitro test method was developed by Obata and Tagami (39) andhas been used to assess topically applied skin moisturizers. This method useshuman stratum comeum combined with moistened filter paper. This uniqueapparatus gave a water gradient across the stratum comeum comparable tothat found in vivo. Using high-frequency conductance measurements, it was

78 MorrisonFigure 14 Measurements of water vapor loss across a nylon film treated with variouslipids (37). Petrolatum provides the best barrier to water vapor, so it reduces watervapor loss by a greater percentage (>95%) than the other lipids.determined that an oil-in-water emulsion and a 10% urea cream both imme-diately increased hydration of the stratum corneum, followed by a decrease inhydration over time. This immediate increase in hydration was ascribed todelivery of water to the stratum corneum by the high water content of thesetwo emulsions. Conversely, a large increase in hydration was not seen by pet-rolatum, but the hydration of the skin model slowly increased for up to 1 hr.At 1 and 2 hr after application of the test material, petrolatum outperformedeach of the emulsions in skin hydration as determined by this test method.While it does not give an immediate boost to skin moisture, Petrolatum hy-drates the skin within minutes to a greater extent and is much \"longer-lasting\"due to its occlusivity. From this information alone, an obvious scenario pre-sents itself to the skin care formulator: obtain the \"best of both worlds\" byincorporating petrolatum in an oil-in-water emulsion.B. Skin Conditioning as a Medical IngredientOcclusion and the subsequent moisturization of skin are properties furnishedby petrolatum which give it wide acceptance as a skin conditioner. These bene-fits of petrolatum also have encouraged physicians and others in the medicalfield to look to this material as an ingredient for use in topical therapeutic

Petrolatum: Conditioning Throughi Occlusion 79products. For example, petrolatum has been recommended as a moisturizerfor diabetics with dry feet (40). The unique occlusive properties of petrolatumalso have enabled it to be used frequently as a healing aid, primarily as aningredient in wound care dressings. Previously, it was noted that petrolatumhelps repair damaged skin (30). These authors are not alone in their percep-tion that petrolatum is good for traumatized skin. The fact that petrolatum bridges the gap between simple skin moisturiza-tion and the treatment of wounded skin was nicely summarized by Kligmanand Kligman (41). They stated that this material is \"a work-horse moisturizerin a variety of settings, for instance after chemical peels and dermabrasions,superficial burns, skin grafts, atopic dry skin and other xerotic rashes.\" Theestablished use of petrolatum in skin care, including medical applications, wasreiterated very clearly by Kligman not long thereafter (42). He noted thatpetrolatum has many uses in the protection of skin against chemical and physi-cal trauma, such as in \"the treatment of cuts, abrasions and burns. It is also amoisturizer par excellence.\"1. Uses on Bums and WoundsThe recommendation to use petrolatum on skin burns goes back many years.It is very likely that this application of petrolatum was initiated not long afterChesebrough's patent, when the medical and pharmaceutical communitiesdiscovered the advantages petrolatum had over the commonly used (at thattime) lard-based ointments. In the 1940s, petrolatum was still being used inthe treatment of skin burns. A textbook of laboratory experiments in organicchemistry recommends using borated petrolatum dressings to treat physicalburns, as well as for chemical burns such as bromine and organic materials(e.g., phenol) (43). Petrolatum has been found to be a favorite burn dressing ingredient formany medical professionals. However, due to the painful, slow-to-heal natureof severely burned skin and its tendency to stick to many burn dressings,medical researchers often look for new or improved materials to be used forbum dressings. In studies like these, the experimental dressings are comparedto a standard, which often is a petrolatum-impregnated gauze (44-46).Similarly, petrolatum-based materials have been used as comparisons inthe development of dressings for skin graft sites (47,48). One alternativeburn dressing which has been developed is a cellulose product which is im-pregnated with a petrolatum-containing emulsion, and is claimed to be nonad-hering (49). Petrolatum also has been claimed as a base for a medicinal salvewhich can be incorporated into a gauze dressing, then applied directly ontotraumatized skin (50), and as a base for a topical antibiotic ointment (51). Bothproducts are said to be useful for treating epidermal trauma, including bumsand wounds.

80 Morrison Other wound care applications of petrolatum include the use of this mate-rial as a dressing in major cancer surgery of the head and neck (52), and as anointment base in the removal of skin grafts from the scalp (53). The ointmentpromotes speedy hemostasis of split-thickness skin donor wounds, thus allow-ing additional skin grafts to be easily taken from nearby areas, without obstruc-tion or delay caused by bleeding from the earlier donor sites.2. Uses to Protect SkinBoth \"petrolatum\" and \"white petrolatum\" have been recognized by the U.S.Food and Drug Administration (FDA) as over-the-counter (OTC) skin-pro-tectant drug products suitable for topical administration (54). When presentat 30-100% of the final product, these materials may be considered OTC skin-protectant active ingredients. The FDA describes a skin protectant as \"a drugwhich protects injured or exposed skin or mucous membrane surface fromharmful or annoying stimuli.\" This skin protection feature has been exploited in many ways. For example,the moisturizing ability of petrolatum has been used to great benefit in pro-tecting the skin of premature infants (55). This protection comes primarily inthe form of enhancing the epidermal barrier, since this barrier does not be-come functionally mature until between 32 and 34 weeks' estimated gesta-tional age. The topical application of a preservative-free anhydrous ointment(ingredients: petrolatum, mineral oil, mineral wax, and wool wax alcohol) wasfound to improve the health of premature infants significantly. The patientswho received this treatment had decreases in three areas studied: TEWL, theseverity of dermatitis, and bacterial colonization of axillary skin. In addition,the authors found that these infants also had fewer microorganism-positivecultures of blood and cerebrospinal fluid. It was postulated that the impairedepidermal barrier of premature infants is an easy route by which bacterialinfection can occur, and the application of the ointment either serves as aprotective skin barrier or causes the skin to improve its natural barrier. Byreducing dermatitis, the ointment also prevents skin cracking which could per-mit easier bacterial invasion. Thus, the application of preservative-free topicalointment was shown to be beneficial and was recommended therapy for pre-mature infants. In other areas of skin protection, petrolatum is not used to prevent watervapor from exiting the skin into the environment; rather, its primary functionas a skin protectant is to stop environmental materials from entering the skin.The skin conditioning result of a protectant and lubricant is that the skin re-mains healthy and is protected from harmful external influences such as fric-tion, chemicals (e.g., detergents), and even dry air. The use of petrolatum as a skin protectant in a medical setting is often as abarrier for incontinent patients. Petrolatum acts as a barrier on the skin from

Petrolatum: Conditioning Through Occlusion 81toxins and excessive moisture in these situations, which is especially importantsince human stool contains caustic enzymes and pathogens (56). Petrolatumhas been claimed as a base for an ointmentlike material which is useful as askin protectant against other biochemical hazards, especially on the hands ofmedical professionals under surgical gloves (57). The protection afforded by petrolatum against nonbiogenic chemical haz-ards also has been documented. A 1990 article reported on the evaluation ofmaterials which were tested for chemical penetration by FT-IR spectroscopy(58). The length of time for ethyl disulfide to penetrate through a barrier thick-ness of 0.45 mm was determined, and it was found that petrolatum resistedpenetration for 22 min, while a polyunsaturated fat allowed ethyl disulfidethrough the barrier after only 5 min. The effective skin protection charac-teristics of petrolatum also have been shown in studies involving exposure tosodium lauryl sulfate (59) and industrial sealants (60). One of the most surprising reports about petrolatum's skin protection waspublished by Kligman and Kligman in 1992 (41). This article referred not topetrolatum's barrier properties against physical or chemical hazards, but to itsprotection against UVB-induced skin damage. These authors found that whenpetrolatum was applied to mouse skin prior to UVB irradiation, a 95% reduc-tion in tumor yield was found. In addition, the incidence of tumors decreasedby 21% when petrolatum was applied after irradiation. It was concluded thatthe number of sunburn cells were reduced by the petrolatum, and that thismaterial also protects against damage to the skin.3. Skin Lubricant UsesThe greaselike consistency of petrolatum and its crude oil origins are obviousindications that this material can perform as a skin lubricant. This property,while certainly meaningful in general skin care, becomes extremely importantin the medical field. The prevention of ulcerated skin such as blisters and bedsores is often an ongoing battle in hospitals all over the world. This greasiness of petrolatum has often been cited as a beneficial quality inskin lubrication. It has been noted that the greasier (or heavier) the product,the better it acts as a lubricant (20). Additionally, these authors stated thatpetrolatum was the recommended lubricant for bedridden patients. It also canbe used as a rectal thermometer lubricant for children (61,62), and petrolatumhas been claimed (likely for its lubrication and protection) as part of a low-irritation shave cream formula (63). Lubrication of the skin is very important in many athletic activities, andpetrolatum has been frequently recommended (64,65). Runners (66,67) andbackpackers often use petrolatum as a blister preventative on their feet, whilethe lubricating and skin protecting properties of petrolatum are utilized byopen-water swimmers to prevent chafing (68).

82 MorrisonC. Hair Conditioning with PetrolatumAs mentioned previously, the primary use of hair conditioning with petrolatumis in the ethnic hair care market, as the main ingredient in anhydrous pomades,solid and semisolid brilliantines, opaque anhydrous hair dressings, and solidpressing oils (69-73). Since pomades are based almost exclusively on petrola-tum, they can sometimes be difficult to remove from the hair. Thus, emulsifiersare sometimes added to the pomade to facilitate this process. Some cosmeticmanufacturers have even been producing \"rinsable pomades,\" which allow theuser to remove the pomade with a minimum of shampooing. Anhydrous po-mades typically are used without any other hair treatment, after washing thehair or after chemically treating the hair (74). Solid and semisolid brilliantinesare used in a manner similar to pomades. Pressing oils are added to the hair immediately before the hair is straight-ened, typically via a hot comb which stretches out the oiled hair. Although thisis an effective method for straightening hair, it does not last very long. (Relax-ers are generally preferred for straightening hair for longer time periods.) The mechanism of how petrolatum conditions in these types of products isstraightforward: physically holding the hair in place, providing lubrication forease of styling and combability, enhancing gloss (oil-based products are natu-rally shiny), and creating a barrier to protect the hair from breakage, externalenvironmental damage, and to keep it from drying out. Petrolatum also canprevent static \"flyaway,\" by creating a film which insulates the hair from thecharges on the surrounding hairs (73). Conditioning with these products hasbeen known for decades, and they are still popular today. Most of the morerecent advances in hair conditioning with petrolatum have come in the formof emulsion products. Within the ethnic market, petrolatum is also a very com-mon ingredient in hair relaxer formulations, acting as a scalp protectant. Sincepetrolatum also aids combing and adds shine to the hair in relaxer formula-tions, it can be considered a hair conditioner to some extent in these products(75). The use of petrolatum as a pomade is well known, but it is still occasionallytrumpeted in the newspapers as \"the secret\" for holding ethnic hair in placeand adding shine (76). Others vary the ingredients to produce slightly differentderivatives which are also used to condition the hair and scalp (77,78). Scien-tists, however, have also developed many hair care product formulations con-taining petrolatum to benefit from this material's properties while minimizingits greasiness. For example, petrolatum can be used to retain moisture andenhance the texture of the hair when used in an emulsified form (79), whichis often more esthetically pleasing than an anhydrous preparation. These conditioning properties of petrolatum have been revealed elsewhere.A rinse-off conditioner formula which contains petrolatum was shown to give

Petrolatum: Conditioning Through Occlusion 83the hair a more smooth and moist texture than an identical formula withoutthe petrolatum (80). One particular hair setting cream which claims to providegloss, antistatic qualities, and good combability has been developed, and sur-prisingly incorporates petrolatum at 10% while a silicone fluid is present atonly 5% (81). A unique \"rinse-on\" conditioner which incorporates petrolatumas a particularly preferred ingredient also has been developed (82). This com-position exists as an oil-in-water emulsion, but inverts to water-in-oil when itis rubbed onto the hair. Conditioning, moisturization, and protection are im-parted to the hair from this nongreasy product. One of the greatest improvements which has been made in hair relaxerformulations is the reduction of irritation from the highly alkaline relaxingagent. Since a strong base is typically needed for these products to performwell, reducing irritation by using a milder active ingredient will give only lim-ited success in relaxing the hair. Even in the case of breakthrough formulas,scalp protectants are still needed to minimize irritation. Examples of improvedhair relaxer formulas have been disclosed (83-87), but the unique nature ofpetrolatum ensures that it is present in both the classic and the newer products.Thus, it is often a preferred ingredient in relaxer formulas.VII. FORMULATING WITH PETROLATUMA. Typical ProceduresJust as the mechanism of hair conditioning with petrolatum is straightforward,so is the procedure of formulating with this material. Since petrolatum is natu-rally resistant to oxidation (due to its saturated hydrocarbon composition), nospecial precautions are necessary when using it to prepare skin and hair carecosmetics. The material is usually melted to obtain homogeneity with otheroily ingredients and can withstand high temperatures, but long-term storageat elevated temperatures or exposure to excessively high temperatures is notrecommended and may eventually cause product decomposition or somesmoking (at very high temperatures). In anhydrous cosmetics such as lip balms, lipsticks, pomades, and topical oint-ments, the usual formulation procedure for incorporating petrolatum is simple: Mix the petrolatum with the other lipophilic ingredients, and heat with stirring at the desired temperature until the mixture is melted and homogeneous. Proceed with further formulation (e.g., adding color or active ingredients) or package the anhydrous product at the desired temperature.For emulsion products, formulating with petrolatum is just as easy. Mix the petrolatum with the other oil phase ingredients and heat to the desired temperature with stirring. Once this phase is uniform and the other, lipophobic

84 MorrisonTable 2 Selected Personal Care Products That May Contain Petrolatum as a Skin orHair ConditionerAfter-sun products Lip balms and creamsAHA creams and lotions Lip glossesAntiperspirants and deodorants LipsticksBaby creams and lotions Makeup foundations and powdersBrilliantines Makeup removersCleansing creams MascarasCold creams Massage productsConcealers MoisturizersDermatological products (e.g., wound care) Night creamsDiaper rash ointments OTC topical pharmaceuticalsDry skin treatments PomadesEye makeup products Protective creams and lotionsFace creams and lotions Scalp creams and lotionsHair conditioners Self-tannersHair dressings Shaving and aftershave productsHair relaxers and straightening products Sunscreen and sunblock productsHair styling aids Suntan productsHand and body creams and lotions Topical ointmentsInsect repellents Waterless hand cleaners ingredients have been suitably prepared, combine the phases in the desired order with sufficient mixing to yield a product of desired consistency.In other words, the petrolatum is treated just like any other oil-phase ingredi-ent when formulating emulsions, be they water-in-oil, oil-in-water, microemul-sions, or multiple emulsions.B. Examples of Formulated ProductsSources of personal care formulations which incorporate petrolatum aboundthroughout the literature and within the cosmetic industry. Examples of pet-rolatum-containing formulations can be found in many of the references listedat the end of this chapter, in supplier formulations, and in trade magazinesand journals (88). While it is not comprehensive. Table 2 lists many types ofpersonal care products in which petrolatum finds application as a hair or skinconditioner. The patent literature is a useful source for uncovering personal careproducts of unique function or formulation. Because of the wide acceptanceand utility of petrolatum as a skin (and, to a lesser extent, hair) conditioner,patented products which contain oily materials will almost always include

Petrolatum: Conditioning Through Occlusion 85petrolatum as a claimed oil-phase ingredient. Some recent examples of patentswhich use petrolatum include anhydrous skin care products (89), emulsionskin and hair care products (90-103), hydroxy acid products (104,105), andskin-lightening cosmetics (106-110). Petrolatum also has been claimed as aningredient in deodorants (111), self-tanners (112), lotioned tissue paper (113,114), powder cosmetics (115), and in a sebum secretion promoter (116), eventhough its use in these products may be perceived as rather unconventional.VIII. SAFETYFrom its infancy, petrolatum has been safely used millions of times on humanhair, skin, and lips. Its safety should be without question, based solely on over100 years' use in real-life situations. However, this material, while known in-dustry-wide (and probably worldwide) as a moisturizer without comparison, isfrequently required to justify its presence in cosmetics when the issue of come-dogenicity arises.A. Comedogenlclty and AcnegenlcltyComedogenicity, or the clogging of skin pores, is often associated (wronglyso) with petrolatum because of its physical characteristics. The heaviness andgreasiness of petrolatum appear to indicate that this material, or a cosmeticingredient which contains it, will be comedogenic or even acnegenic (causesacne). After all, if a consumer has oily skin and acne, why should he or she justput more oil on it? This argument may seem valid to the uninitiated; however,skin oil (sebum) does not have the same chemical composition as petrolatum. In fact, at cosmetic industry conferences and seminars, many misinformedpeople (scientists and nonscientists alike) are often heard saying things like,\"Well, everyone knows that petrolatum clogs the pores.\" The evidence clearlyshows otherwise. Some crude versions of petrolatum which were manufac-tured during its early years may have contained impurities and caused someproblems, but the petrolatum from current production methods is completelynoncomedogenic. Petrolatum samples once reported to be comedogenic werelater found to be \"false positives,\" and these substances were not comedogenicat all, either in the broadly used rabbit ear assay or in humans (117). In addition, studies done by Fulton (118) and Lanzet (119) showed thatpetrolatum gave no comedogenic response whatsoever in the rabbit ear assay.Interestingly, Fulton found that many of the ingredients which cosmetic for-mulators often use as nonoily substitutes for petrolatum (e.g., when preparing\"oil-free\" products) are strongly comedogenic. Since dilution effects on thecomedogenic potential of ingredients cannot be easily determined, it is nec-essary for the formulator to test the complete, fully formulated product for

86 Morrisoncomedogenicity. Nevertheless, it is reassuring to know that petrolatum will notcause comedone formation, so it can be considered a safe ingredient to use.Petrolatum has also been cited as a moisturizer for patients with acne andacne-prone skin (117,118). The issue of comedogenicity was considered at a 1988 American Academyof Dermatology Invitational Symposium on Comedogenicity (120). At thisconference, the attendees stated that \"neither the consumer nor the physiciancan assess whether the formulation will be acnegenic by simple inspection ofthe product or by examining the list of ingredients. Furthermore, the product'sphysical characteristics, such as oiliness or viscosity, are not in themselves pre-dictors of an acnegenic response.\" Thus, it is clear that the physical propertiesof petrolatum do not predict acnegenicity or comedogenicity (117,120).B. AllergenlcityIt also is known that petrolatum does not cause allergic reactions. In fact, thisneutrality is why petrolatum is commonly used as a carrier for the topical ap-plication of hydrophobic materials in human patch tests for sensitization (121,122), in studies on transdermal absorption (123), and in the treatment ofcertain diseases (124). A study also has been performed to evaluate the rela-tionship between materials applied to the skin of infants and eventual atopicdermatitis (125). These authors found no evidence that the use of emollients(petrolatum was used most frequently) on children caused the eventualdevelopment of atopic dermatitis (AD). They concluded that petrolatum \"cansafely be used in the skin care of AD susceptible individuals.\"C. IrritationSince petrolatum is frequently used as an ointment base and as a vehicle fortopical patch applications, it may be expected that petrolatum is nonirritatingto skin. This is the case, and such nonirritation has been proven by decades ofhuman use. Therefore, the irritation potential of petrolatum has under-standably been rarely studied over the years. In 1979, Motoyoshi determinedthat petrolatum is a nonirritant on both miniature swine skin (an acceptablesubstrate for determining skin irritation) and human skin (126). Petrolatumhas also been compared to other materials in an evaluation of their dermatiticproperties when used as cutting waxes (127). When tested fresh and after re-constitution, petrolatum produced no significant dermatological lesions, thusattesting to its nonirritancy. It is clear that petrolatum is a safe material for all skin and hair care use,and holds no potential for comedogenicity, allergenlcity, or irritation. In ad-dition, studies have shown that petrolatum and other topical hydrocarbonsremain in the stratum corneum and do not penetrate to the deeper layers of

Petrolatum: Conditioning Through Occlusion 87skin (30,123). The human use of this material on skin and hair for over a cen-tury is more evidence that might ever be necessary to determine the safety ofa product, and it shows that petrolatum is indeed an exceedingly safe materialfor skin and hair care applications, either neat or as a part of a formulatedpersonal care product.IX. CONCLUSIONS AND THE FUTURE OF PETROLATUM IN COSMETICSPetrolatum has been shown to be a safe and effective ingredient for hair andskin conditioning. Its ability to moisturize is unrivaled, and it has been usedcontinuously in hair products for decades, despite frequent changes in fashionand hair styles. Petrolatum is a superb wound ointment and an excellent skinprotectant. Therefore, it is doubtful that this ingredient will fall out of favor inthe foreseeable future. Based on its conditioning properties, its natural origins,its safety, its ease of formulation, and its low cost relative to other materials,this substance should be a constant in the ever-changing field of personal careingredients. Although petrolatum has changed little since it was first reportedby Chesebrough, it has never been duplicated synthetically. The unique physi-cal properties and conditioning abilities of petrolatum will bolster its use incosmetic products for years to come. Indeed, the future is bright for petrola-tum, a true workhorse of the personal care industry.REFERENCES 1. Speight JG. The Chemistry and Technology of Petroleum. New York: Marcel Dek- ker, 1980:1-4. 2. Uhl WC. Introduction. In: Bland WF, Davidson RL, eds. Petroleum Processing Handbook. New York: McGraw-Hill, 1967:1-1. 3. Kalichevsky VA, Peters EH. The Raw Material, Crude Petroleum and Natural Gas. In; Guthrie VB, ed. Petroleum Products Handbook. New York: McGraw- Hill, 1960:1-5. 4. Speight J. Petroleum (Refinery Processes). In: Kroschwitz JI, exec, ed., Howe- Grant M, ed. Kirk-Othmer Encyclopedia of Chemical Technology. Vol. 18.4th ed. New York: Wiley, 1996:434. 5. Jakubke H-D, Jeschkeit H, eds. Concise Encyclopedia Chemistry. Beriin: Walter De Gruyter, 1993. 6. Sage LL. Cosmetics—^past, present, future. In: DeNavarre MG, ed. The Chemistry and Manufacture of Cosmetics. Vol. III. 2d ed. Wheaton IL: Allured, 1988:1-6. 7. Rieger MM. Cosmetics. In: Kroschwitz JI, exec, ed., Howe-Grant M, ed. Kirk-Othmer Encyclopedia of Chemical Technology. Vol. 7.4th ed. New York: Wiley, 1996:573. 8. Busch P. The historical development of cosmedc science. In: Umbach W, ed. Cos- metics and Toiletries: Development, Production and Use. Chichester, UK: Ellis Horwood, 1991:1-7.

88 Morrison 9. Wigoder G, general ed. Illustrated Dictionary and Concordance of the Bible. Je- rusalem: G.G. The Jerusalem Publishing House, 1986.10. See: 2 Kings 9:30, Jeremiah 4:30, Ezekiel 23:40, and Proverbs 6:25.11. Job 42:14.12. Chesebrough RA. U.S. Patent 127,568 (June 4,1872).13. Throughout this chapter, the generic name \"petrolatum\" will be used in instances where previous authors have called this material by other names, such as Vaseline, CosmoUne, and Petroline.14. Schindler H. Petrolatum for drugs and cosmetics. Drug Cosmet Ind 1961; 89(1): 36-37,76,78-80, 82.15. Crew BJ. A Practical Treatise on Petroleum. London, 1887: Henry Carey Baird & y Co.16. Sachanen AN. The Chemical Constituents of Petroleum. New York: Reinhold, 1945:284.17. Meyer E. White Mineral Oil and Petrolatum and Their Related Products. New York: Chemical Publishing Company, 1968:16.18. A striking analogy between the refining of petroleum and the refining of gold ore has been made. See: Morrison DS, Schmidt J, PauUi R. The scope of mineral oil in personal care products and its role in cosmetic formulation. J Appl Cosmetol 1996; 14:111-118.19. Blank IH. Factors which influence the water content of the stratum corneum. J Invest Dermatol 1952; 18:433-440.20. Lazer AP, Lazer P. Dry skin, water, and lubrication. Dermatol Clin 1991; 9(1): 45-51.21. Rieger M. Skin care: new concepts vs. established practices. Cosmet Toilet 1991; 106(ll):55-58,60-62,64,66,68.22. Steenbergen C. Petroleum derivatives as moisturizers. Am Cosmet Perf 1972; 87(3):69-70,72.23. Fishman HM. Treating dry skin. Household Pers Prod Ind 1994; 31(2):30.24. Fisher AA, Pincus SH, Storrs FJ, Richman E. When to suspect cosmetic dermatitis. Patient Care 1988; 22(11):29.25. Idson B. Dry skin: moisturizing and emoUiency. Cosmet Toilet 1992; 107(7):69-72, 74-76,78.26. Levine N. Advise patients on proper cosmetic use. Dermatol Times 1990 (Oct.):l.27. Kligman AM. Regression method for assessing the efficacy of moisturizers. Cos- met Toilet 1978; 93(4):27-35.28. Grove GL. Noninvasive methods for assessing moisturizers. In: Waggoner WC, ed. Clinical Safety and Efficacy Testing of Cosmetics. New York: Marcel Dekker, 1990:121-148.29. Brown BE, Diembeck W, Hoppe U, Elias PM. Fate of topical hydrocarbons in the skin. J Soc Cosmet Chem 1995; 46:1-9.30. Ghadially R, Halkier-Sorenson L, Elias PM. Effects of petrolatum on stratum corneum structure and function. J Am Acad Dermatol 1992; 26(3):387-396.31. Loden M. The increase in skin hydration after application of emollients with dif- ferent amounts of lipids. Acta Dermatol Venereol (Stockh) 1992; 72:327-330.

Petrolatum: Conditioning Through Occlusion 8932. Prall JK, Theiler RF, Bowser PA, Walsh M. The effectiveness of cosmetic products in alleviating a range of skin dryness conditions as determined by clinical and in- strumental techniques. Int J Cosmet Sci 1986; 8:159-174.33. Tsutsumi H, Utsugi T, Hayashi S. Study on the occlusivity of oil films. J Soc Cosmet Chem 1979; 30:345-356.34. Rietschel RL. A method to evaluate skin moisturizers in vivo. J Invest Dermatol 1978; 70(3):152-155.35. Wepierre J. Study of the hydrating effect of cosmetic preparations by measuring cutaneous impedance in the hairless rat. Soap Perfum Cosmet 1977; 50(12): 506-509.36. Fromder A, Lippold BC. Water vapour transmission and occlusivity in vivo of lipophilic excipients used in ointments. Int J Cosmet Sci 1993; 15:113-124.37. Tranner F, Berube G. Mineral oil and petrolatum: reliable moisturizers. Cosmet Toilet 1978; 93(3):81-82.38. Friberg SE, Ma Z. Stratum corneum lipids, petrolatum, and white oils. Cosmet Toilet 1993; 108(7):55-59.39. Obata M, Tagami H. A rapid in vitro test to assess skin moisturizers. J Soc Cosmet Chem 1990; 41:235-241.40. U.S. Department of Health and Human Services. Diabetic neuropathy: the nerve damage of diabetes. Pamphlet, September 1991.41. Kligman LH, Kligman AM. Petrolatum and other hydrophobic emollients reduce UVB-induced damage. J Dermatol Treatment 1992; 3:3-7.42. Kligman AM. Why cosmeceuticals? Cosmet Toilet 1993; 108(8):37-38.43. Adams R, Johnson JR. Elementary Laboratory Experiments in Organic Chemis- try. 3d ed. New York: Macmillan, 1940:415.44. Guilbaud J. European comparative clinical study of Inerpan: a new wound dressing in treatment of partial skin thickness burns. Burns 1992; 18(5):419-422.45. Gao ZR, Hao ZQ, Li Y, Im MJ, Spence RJ. Porcine dermal collagen as a wound dressing for skin donor sites and deep partial skin thickness burns. Burns 1992; 18(6):492-496.46. Eloy R, CorniUac AM. Wound healing of burns in rats treated with a new amino acid copolymer membrane. Burns 1992; 18(5):405-411.47. Sawada Y, Sone K. Beneficial effects of silicone cream on grafted skin. Br J Plast Surg 1992; 45(2):105-108.48. Sawada Y, Sone K. Benefits of silicone cream occlusive dressing for treatment of meshed skin grafts. Burns 1992; 18(3):233-236.49. Markintel 1993 (Mar. 1):1-15.50. Whitham J. Medicinal salve composition. U.S. Patent 5,270,042 (Dec. 14,1993).51. Shinauh WK. Topical ointment for the treatment of epidermal trauma. U.S. Patent 5,407,670 (Apr. 18,1995).52. Phan M, Van der Auwera P, Andry G, et al. Wound dressing in major head and neck cancer surgery: a prospective randomized study of gauze dressing vs sterile vaseline ointment. Eur J Surg Oncol 1993; 19(1):10-16.53. Sawada Y, Ara M, Yotsuyanagi T. A thrombin ointment that achieves rapid haem- ostasis of split thickness donor wounds, particularly on the scalp. Burns 1991; 17(3): 225-227.

90 Morrison54. 48 Fed Reg 6820 (Feb. 15,1983).55. Nopper AJ, Horii KA, Sookdeo-Drost S, Wang TH, Mancini AJ, Lane AT. Topical ointment therapy benefits premature infants. J Pediatr 1996; 128(5):660-669.56. Maklebust J. Pressure ulcer update. RN1991; 54(12):56-64.57. Lemole GM. Protective gel composition. U.S. Patent 5,019,604 (May 28,1991).58. Braue EH Jr, Pannella MG. Topical protectant evaluation of FT-IR spectroscopy. Appl Spectrosc 1990; 44(6): 1061-1063.59. Liu JC, Huang MJ, Sun Y, Chien YW. The effect of barrier creams on the electrical conductivity of excised skin during exposure to detergents. J Soc Cosmet Chem 1987; 38:63-75.60. Shulakov NA, Novikov VE, Loseva VA, et al. Vaseline protection of the skin from the effects of the sealent Uniherm-6. Gig Tr Prof Zabol 1990; 12:43-44.61. Nestruk C, Sangiorgio M. Colds, kids & you. Prevention 1992; 44(l):58-67.62. Kennedy B. Babes in the woods. Rodale's Guide to Family Camping, 1995 (Spring); 1(1):16,18,20-24,128.63. Curtis AW. Less irritating shaving material. U.S. Patent 5,252,331 (Oct, 12,1993).64. Fitness 1995 (May):101.65. Ramsey ML. Managing friction blisters of the feet. Physician and Sportsmedicine 1992; 20(1):116-121.66. Pate D. Success secrets for runners. Health & Fitness Magazine, 1994 (Dec.): 34-35.67. Kuscsik N. That first marathon. Women's Sports and Fitness 1989; ll(8):20-25.68. Zempel C. Take to the waves! Women's Sports and Fitness 1989; 11(4):66.69. Goode ST. Hair pomades. Cosmet Toilet 1979; 94(4):71-74.70. Syed AN. Ethnic hair care: history, trends and formulation. Cosmet Toilet 1993; 108(9):99-102,104-107.71. Lochhead RY, Hemker WJ, Castaiieda JY. Hair care gels. Cosmet Toilet 1987; 102(10):89-100.72. Mottram FJ. Hair treatments. In: Butler H, ed. Poucher's Perfumes, Cosmetics and Soaps. Vol. 3.9th ed. London: Chapman & Hall, 1993:130-169,73. Jellinek JS, Formulation and Function of Cosmetics, New York: Wiley-Inter- science, 1970:457-471.74. BSUert V, Siemers H. Hair Care Products. In: Umbach W, ed. Cosmetics and Toiletries: Development, Production and Use. Chichester, UK; Ellis Horwood, 1991:190-201.75. Obukowho P, Birman M. Hair curl relaxers. Cosmet Toilet 1995; 110(10):65-69.76. Nelson J. I love Vaseline; it comes in tubs and tins, protects babies' bottoms, tames teenage hairdos, softens women's lips and is absolutely essential to life as we know it. Washington Post Magazine 1987 (Jan, ll):w27.77. McCarthur CM. Hair dressing cosmetic, U.S. Patent 3,932,611 (Jan. 13,1976),78. Vernon DM. Hair treatment composition and method. U.S. Patent 4,999,187 (Mar. 12,1991).79. Tada T, Myamoto N. Hair conditioners containing vaseline, JP 03 264,516 (Nov. 25,1991). Chem Abstr 1992; 116:158567p.80. Fujikawa M, Suzuki N. Hair conditioners containing methylpolysiloxanes, protein derivatives, and vaseline, JP 03 264,515 (Nov. 25,1991). Chem Abstr 1992; 116: 136011a.

Petrolatum: Conditioning Tiirougii Occiuslon 91 81. Hasegawa M, Yoda E, Yogoshi M, Koresawa T. Hair-setting preparations con- taining branched esters and silicone oil. JP 07 25,733 (Jan. 27,1995). Chem Abstr 1995; 122:196547p. 82. Wagman J, Sajic B. Skin and hair conditioner compositions and conditioning method. U.S. Patent 4,551,330 (Nov. 5,1985). 83. Patel MM. Conditioning and straightening hair relaxer. U.S. Patent 5,476,650 (Dec. 19,1995). 84. Cowsar DR, Adair TR. Hair relaxer compositions containing strong base and alkaline earth metal hydroxides. WO 95 03,031 (Feb. 2,1995). Chem Abstr 1995; 122:196539n. 85. Hawkins GR, Simpson CB Jr, Klein GJ. Hair relaxer composition and associated methods. U.S. Patent 5,304,370 (Apr. 19,1994). 86. Akhtar M. Hair relaxer cream. U.S. Patent 5,171,565 (Dec. 15,1992), 87. McKaba W, Simpson CB. Quaternary ammonium hydroxide hair relaxer compo- sition. U.S. Patent 4,530,830 (July 23,1985). 88. Morrison DS. Petrolatum: a useful classic. Cosmet Toilet 1996; lll(l):59-66,69. 89. Swenson RH. Skin care formulation. U.S. Patent 5,494,657 (Feb. 27,1996). 90. Cho SH, Frew U, Chandar P, Madison SA. Synthetic ceramides and their use in cosmetic compositions. U.S. Patent 5,476,671 (Dec. 19,1995). 91. Rose W, Zimmerman AC. Petroleum jelly cream. U.S. Patent 5,407,678 (Apr. 18,1995). 92. Rawlings AV, Watkinson A. Skin care method and composition. U.S. Patent 5,554,366 (Sept. 10,1996). 93. Amin MK, Butter SS. Topical composition for skin treatment containing an iso- quinoline and a vasodilator. GB 2,290,470 (Jan. 3,1996). Chem Abstr 1996; 124: 155717s. 94. Kikuchi H, Tsubone K. Moisturizing emulsion-type skin cosmetics containing ammonioethyl phosphates and surfactants. JP 08 113,527 (May 7,1996). Chem Abstr 1996; 125:67275m. 95. Sato K, Mizutani M, Yamane T. Method for manufacturing cosmetic emulsions. JP 08 99,835 (Apr. 16,1996). Chem Abstr 1996; 125:67210m. 96. Jokura Y, Uesaka T, Honma S, Kato Y, Ishida K. Moisturizing cosmetic contain- ing ceramide and dicarboxylic acid. DE 19,539,016 (Apr. 25,1996). Chem Abstr 1996; 124:352348y. 97. Sakamoto O, Yanagida T, Yonezawa K. Water-in-oil skin preparations of a- tocopheryl retinoate. JP 08 99,834 (Apr. 16, 1996). Chem Abstr 1996; 125: 41495h. 98. Hikima T. Skin cosmetics containing Pyracanthafortuneana fruit extracts and other ingredients. JP 08 133,959 (May 28,1996). Chem Abstr 1996; 125:123293e. 99. Nakamura T, Kaneki H, Ito K. Water/oil-type cosmetic emulsions. JP 08126,834 (May 21,1996). Chem Abstr 1996; 125:123257w.100. Staeb F, Landenzoerfer G. Cosmetic or dermatologic compositions containing cinnamic acid derivatives and flavonoid glycosides. EP 716,847 (June 19,1996). Chem Abstr 1996; 125:95577e.101. Doughty DG, Gatto JA, Nawaz Z, Rolls RGA. Skin care oil-in-water dispersions. WO 96 16,545 (June 6,1996). Chem Abstr 1996; 125:95591e.

92 Morrison102. Doughty DG, Gatto JA, Weisgerber DJ, Schwartz JR, Topical skin care com- positions containing non-occlusive liquid polyol carboxylic acid esters as skin conditioning agents. WO 96 16,637 (June 6, 1996). Chem Abstr 1996; 125: 95592f.103. Murase T, Hase T, Takema Y, Ogawa A, Oosu H, Tokimitsu I. Cosmetics con- taining stilbenes for prevention of wrinkles. JP 08 175,960 (July 9,1996). Chem Abstr 1996; 125:177025n.104. Smith WP. Low irritant skin-cosmetic composition for daily topical use, its appli- cation and manufacture. U.S. Patent 5,520,918 (May 28,1996).105. Maurin E, Sera D, Guth G. Cosmetic compositions containing an enzyme and a hydroxyacid precursor. FR 2,725,898 (Apr. 26, 1996). Chem Abstr 1996; 125: 67189m.106. Yoshioka M, Iwamoto A, Masaki H. Skin-lightening cosmetics containing plant extracts as tyrosinase inhibitors. JP 08104,646 (Apr. 23,1996). Chem Abstr 1996; 125:67215s.107. Itokawa H, Morita H, Takeya K, et al. Skin-lightening cosmetics containing cy- clopeptide Pseudostellarins extracted from Pseudostellaria heterophylla roots as tyrosinase inhibitors and melanin formation inhibitors. JP 07 324,095 (Dec. 12, 1995). Chem Abstr 1996; 124:241760g.108. Yagi E, Komazaki H, Shibata Y, Naganuma M, Fukuda M. Skin-lightening cos- metics containing melanin formation inhibitors from Quararibea amazonia. JP 08 12,556 (Jan. 16,1996). Chem Abstr 1996; 124:211546z.109. Ochiai M, Tada A, Yokoyama Y, Nozawa S, Reduced ionones as melanin forma- tion inhibitors and topical preparations containing them. JP 08 73,334 (Mar. 19, 1996). Chem Abstr 1996; 125:67246c.110. Tada A, Yokoyama Y, Ochiai M, Nozawa S. Melanin formation inhibitors com- prising reduced ionones and skin preparations containing them. JP 08 73,335 (Mar. 19,1996). Chem Abstr 1996; 125:41476c.111. McCuaig D. Long-life deodorant composition containing zinc oxide and starch. CA 2,130,967 (Feb. 27,1996). Chem Abstr 1996; 124:298463s.112. Philippe M, Tuloup R, De Salvert A, Sera D, Fodor P. Cosmetic compositions containing a precursor of dihydroxyacetone. EP 709,081 (May 1,1996). Chem Abstr 1996; 125:41447u.113. Klofta TJ, Warner AV. Lotioned tissue paper and impregnation composition for its manufacture. WO 95 35,412 (Dec. 28,1995). Chem Abstr 1996; 124:179297f.114. Klofta TJ, Warner AV. Lotioned tissue paper and impregnation composition for its manufacture. WO 95 35,411 (Dec. 28,1995). Chem Abstr 1996; 124:179298g.115. Nakajima H. Water-repellent powders overcoated with solid oily substances and powdery cosmetics containing them. JP 08 59,431 (Mar. 5, 1996). Chem Abstr 1996; 124;352342s.116. Hanamura A, Sata A. Sebum secretion promoters containing bryonolic acid. JP 07 109,214 (Apr. 25,1995). Chem Abstr 1995; 123:40736j.117. Kligman AM. Petrolatum is not comedogenic in rabbits or humans: a critical reappraisal of the rabbit ear assay and the concept of \"acne cosmetica.\" J Soc Cosmet Chem 1996; 47(l):41-48.

Petrolatum: Conditioning Through Occlusion 93118. Fulton JE Jr, Pay SR, Fulton JE III. Comedogenicity of current therapeutic prod- ucts, cosmetics, and ingredients in the rabbit ear, J Am Acad Dermatol 1984; 10:96-105.119. Lanzet M. Comedogenic effects of cosmetic raw materials. Cosmet Toilet 1986; 101(2):63-64,66-68,70,72.120. American Academy of Dermatology Invitational Symposium on Comedogenic- ity. J Am Acad Dermatol 1989; 20:272-277.121. Brandrup F, Menne T, Agren MS, Stromberg HE, Hoist R, Frisen M. A random- ized trial of two occlusive dressings in the treatment of leg ulcers. Acta Dermatol Venereol (Stockh) 1990; 70(3):231-235.122. Old problems from new sensitizers. Dermatol Times 1991 (Mar.):34.123. Brown BE, Diembeck W, Hoppe U, Elias PM. Fate of topical hydrocarbons in the skin. J Soc Cosmet Chem 1995; 46(l):l-9.124. Ceilley RI, Goldberg GN, Prose NS. A guide to pediatric rashes. Patient Care 1989; 23(15):150-160.125. Macharia WM, Anabwani GM, Owili DM. Effects of skin contactants on evolu- tion of atopic dermatitis in children: a case control study. Trop Doct 1991; 21:104- 106.126. Motoyoshi K, Toyoshima Y, Sata M, Yoshimura M. Comparative studies on the irritancy of oils and synthetic perfumes to the skin of rabbit, guinea pig, rat, mini- ature swine and man. Cosmet Toilet 1979; 94(8):41^3,45-48.127. Ireson JD, Leshe GB, Osborne H, Read M. A laboratory investigation of a selec- tion of lubricant waxes as dermatitic agents. Pharmacol Res Commun 1972; 4(4): 353-356.

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5Humectants in Personal CareFormulation: A Practical GuideBruce W. GessleinAjinomoto U.SA., Inc., Teaneck, New JerseyI. INTRODUCTIONCompounds that can improve the surface of skin or hair are called condition-ing agents. The mechanisms by which conditioning compounds do this varydepending on the type of compound and surface to which they are applied to.One of the primary methods by which conditioning ingredients function is byregulating the amount of moisture in the skin or hair. Since moisture is a keyfactor in the condition of both hair and skin, ingredients which affect moisturelevels are potentially conditioning agents. Humectants are conditioning agents that regulate water levels on the skinand hair in a distinct way. Due to their chemical nature, they are able to attractand bind water to themselves. This property is known as hygroscopicity. Byutilizing this useful property, formulators have been able to incorporatehumectants effectively in conditioning products for skin and hair. While thereare both inorganic and organic materials which have this property, only or-ganic ones have generally been used in cosmetic products. Humectants have been said to have the ability to rehydrate the skin whendelivered from a cream or lotion. In shampoos and conditioners they are saidto soften the hair and in fact to swell the hair shaft. They may also help plas-ticize the films of certain polymers, and are often used as co-solvents duringthe solubilization of fragrances or oils into products. Some humectants havethe reported ability to enhance the efficacy of preservative systems. 95

96 Gesslein The primary humectant used in personal care products is glycerin (orglycerol). It is a trihydric alcohol that is chiefly derived from fats and oils andas a by-product from soap manufacture. This semisweet, clear liquid has beenshown to have conditioning benefits when applied to skin. Additionally, it alsoprovides many other benefits to formulations via its water-regulating ability.Glycerin's versatility coupled with its relatively low cost and low toxicity hasmade it a favorite among formulators for decades. Other important humectantsinclude sorbitol, propylene glycol, and other polyhydric alcohols. Some metal-organic types have been gaining popularity due to their greater hygroscopiccharacteristics. These include types like sodium PCA and sodium lactate. In this chapter we will discuss the properties of humectants commonly usedin today's practice. The basic theory of how and why humectants are usedwill be given, based on the experiments and experience of past investigators.Newer and exciting work will be referenced, and some original work will beoutlined. Formulations and test results will be given to demonstrate the mattercovered.II. HISTORICAL DEVELOPMENTHumectants have been known and used in skin treatment products for thou-sands of years. One of the earliest applications was a hand cream made up of50% humectant and 50% water (1). In addition to being the most widely usedhumectant in personal care formulation, glycerin is also the oldest. In 1779,the Swedish chemist K. W. Scheele (1742-1786) discovered glycerin by acci-dent when he was investigating a soap plaster by heating a mixture of olive oiland lead monoxide. The material he called \"sweet principle of fat\" we now callglycerin. He later determined that the same reaction which produced glycerinand soap occurred when other metals and glycerides were heated together.Scheele published his findings in 1783 in the Transactions of the Royal Academyof Sweden. In 1811 the French investigator Chevreul (1786-1889) named Sheele'ssweet principle of fat glycerin, from the Greek gfykys (meaning sweet). In 1823he obtained the first patent pertaining to the production of fatty acids fromfats and oils. This patent also contained a method for the recovery of glycerinthat was released during the process. Pelouze, another French scientist, deter-mined the empirical formula for glycerin in 1836, and the structure was pub-lished 47 years later (2). Over time scientists realized that glycerin was presentin all animal and vegetable fats and oils. Improved methods of isolating andproducing it on a commercial scale were developed. Soap manufacturers ledthe way in this endeavor with large-scale glycerin production beginning duringthe early 1900s. Methods for producing synthetic glycerin were developed asa result of high demand brought on by the war during the 1930s and 1940s.

Humectants In Personal Care Formulation 97 Since glycerin had desirable humectant properties, was relatively inexpen-sive, and was readily available, it became incorporated in a wide variety ofpersonal care products. With the advent of World War II, however, glycerinwas needed for military use, and other humectants were pressed into service(3). Polyols such as sorbitol and propylene glycol were most used, though theywere not perfect glycerin replacements. These materials remain today someof the most widely utilized humectants after glycerin.III. NONCOSMETIC USES OF HUMECTANTSThe versatility of humectants is evidenced by the numerous ways in which theyfind application. Since they have the ability to reduce the freeze point of solu-tions, they are frequently used as antifreezes in cooling systems. They are alsoused in the manufacture of products such as printing rolls, glues, leather, al-cohol, nitroglycerol (dynamite), and tobacco. Humectants ensure a smoothflow of ink in writing instruments and prevent crusting on the pen point. Incandy manufacturing, sorbitol is used to extend shelf life by inhibiting thesolidification of sugar. They are also used as food sweeteners, texturizers, andas a softener in peanut butter. Finally, humectants have been used to increasethe absorption of vitamins in pharmaceutical preparations (4).IV. HUMECTANCYThe key characteristic of a humectant is hygroscopicity. Hygroscopicity is theability of a material to hold (or bind) moisture to itself. A useful humectantwill retain moisture over a wide range of humidity conditions and for an ex-tensive time period. There are two ways of expressing the hygroscopicity ofa humectant: (1) equilibrium hygroscopicity and (2) dynamic hygroscopicity.Both these descriptors are important in choosing a humectant for personalcare applications.A. Equilibrium HygroscopicityEquilibrium hygroscopicity is the measure of water held by a humectant whenthere is equilibrium between the material and the relative humidity of theair. An effective humectant should exhibit a high equilibrium hygroscopicity.Equilibrium hygroscopicity is expressed as the weight percent of water held bythe humectant divided by the relative humidity: To measure the equilibrium hygroscopicity of a humectant, one exposeshumectant solutions of known concentration to various controlled relative

98 Gessleinhumidities. The weight of the solution is taken periodically. A curve is thenplotted contrasting the weight of water held by the humectant versus the rela-tive humidity. As an example, it is found that at 50% relative humidity the Hefor glycerin is —25%, and for propylene glycol it is —20%.B. Dynamic HygroscopicityDynamic hygroscopicity is an expression of the rate at which a humectant gainsor loses water when approaching equilibrium. An ideal humectant should ex-hibit low dynamic hygroscopicity, which indicates that it is able to retain mois-ture for a long period of time. Since there are no direct methods, no absolutemeasures, to determine dynamic hygroscopicity, it is necessary to compare onehumectant relative to another. Glycerin is often used as the known humectant.In this work it has been found that sorbitol exhibits the lowest dynamic hygro-scopicity of the more commonly used humectants.V. THE iDEAL HUiViECTANT FOR COSiViETIC PRODUCTSWhile many different materials exhibit humectancy, not all are appropriatefor use as a conditioning ingredient. There are several desirable propertiesthat should be exhibited by a humectant. Griffin et al. delineated the desirableproperties that an ideal humectant should possess (5). A summary of theseimportant properties follows. 1. A humectant should be able to absorb a great deal of moisture from the air at a broad range of relative humidities. 2. Its moisture content should change little when exposed to large changes in relative humidity. 3. It should be nontoxic. 4. A humectant should exhibit good color properties. 5. It should be of low viscosity to facilitate incorporation into systems. 6. A humectant should be nonreactive with commonly used materials, and it should be noncorrosive to commonly used packaging. 7. It should be readily available and relatively low in cost.The above list describes an ideal humectant; however, none of the materialsused today exhibits all of these properties. Glycerin is perhaps the most nearly\"ideal\" of all the available humectants.VI. FORIVIULATING WITH HUMECTANTSHumectants are used in formulations for more than just their effects on skinand hair. They have been shown to have an important effect on a product's

Humectants in Personal Care Formulation 99freezing point and to affect the solubility of certain compounds. Also, theyhave been shown to increase product viscosity, retard the evaporation of water,and act as a preservative and an emulsion stabilizer. One of the aspects of humectants that is important, but not always appre-ciated, is their ability to couple mutually incompatible materials together. Thehumectant can act as a co-solubilizer for many materials in creating a clearsolution. The classic example of this is the coupling ability of glycerin withsodium stearate in the formation of \"clear\" bar soaps. In fragrance solubi-lization, materials such as propylene glycol, or dipropylene glycol are oftenused as a \"co-solvent\" in conjunction with solubilizing materials such aspolysorbate-20. Polyols are known to depress the freezing point of water solutions. TheCRC Handbook of Chemistry and Physics includes a number of tables deline-ating the freezing-point depression of polyols in water solutions by concentra-tion (6). Humectants are added to water-based systems, especially surfactantcleansers, to maintain clarity at low temperatures during shipping and to pre-vent bottle cracking. The clarity of a surfactant cleansing system is maintainedchiefly through the polyol-humectant's ability to act as a co-solvent and anti-freeze for fatty materials, making it more difficult for these materials to comeout of solution. As the ambient temperature decreases, the longer-chain-lengthfatty materials freeze out of solution first, followed by the shorter-chain-lengthmaterials. At these reduced temperatures, their solubility in the surfactantsolution is significantly reduced. The addition of a polyol humectant helps toenhance the solubility of these fats in the system. Bottle cracking is a phenomenon that may occur when water-based systemsin sealed containers with insufficient expansion space are exposed to tempera-tures low enough for the formulation of ice. As ice crystals form, an expansionof the water contained in the product occurs that may be great enough to stressthe packaging to the point of breakage. The polyol-humectants act as anti-freeze, much the same as the antifreeze in a car's radiator, by reducing thefreezing point of water to a point where ice does not form at the temperaturesexpected during shipping and storage.VII. TYPES OF HUMECTANTSAs suggested, humectants are conditioning agents which have the ability toattract and bind water. Because of this they are able to regulate the exchangeof moisture between a surface, such as hair or skin, and the air. By increasingthe level of moisture in the skin, its condition is improved. Hair also exhibitsimproved condition when it is moisturized; however, the effectiveness ofhumectants in hair is less than that of skin.

100 Gesslein Humectants can generally be classified as either inorganic, metal-organic,or organic. With the exception of the inorganic class, all these materials findextensive use in personal care formulations. Humectants have a long historyof use in personal care formulation. It has been stated that some of the earliesthand creams were a mixture of 50% humectant and 50% water. Nearly everypersonal care product contains a hygroscopic material for one purpose or an-other. In some cases the material is intended to protect the product from dry-ing out and shrinking, or to prevent rolling up on application. In other casesthe humectant is intended to have a real effect on the skin or the hair.A. Inorganic HumectantsInorganic humectants are typically the salts of inorganic acids. Calcium chlo-ride is an example of this class. There is currently little use for this class ofhumectant in personal care formulation, because they have problems relatedto their corrosive effects and incompatibility with other raw materials (7). Ad-ditionally, since these materials are salts, their incorporation in personal careformulations, at amounts necessary to deliver substantial humectancy, can de-tract from the other desired properties of the formulation. For example, emul-sion products such as creams and lotions have a tendency to destabilize dueto the salting-out effect. The effect on surfactant-based cleansing products iswell established; they cause the system to go beyond the peak of the salt curve,lowering viscosity and often depressing foam. These materials also tend toincrease the potential for eye sting and irritation, and in powdered products,may desiccate the skin to an extent.B. Metal-Organic HumectantsThe metal-organic class of humectants is much more useful. These materials,which contain a mixture of a metal ion and an organic portion, are usually thesalts of strong bases and weak organic acids. Sodium lactate and sodium PCA(pyrrolidone carboxylic acid) are typical examples and are perhaps the mostwidely used of this class of humectants,C. Organic HumectantsThe organic humectant class is the broadest and the most widely used in per-sonal care formulation. These materials are typically polyhydric alcohols andtheir esters and ethers. Glycerin, propylene glycol, and sorbitol are the mostcommon examples. The simplest unit is ethylene glycol, and a series can bebuilt by the addition of ethylene oxide to the basic unit. This leads to a seriescomposed of ethylene glycol, propylene glycol, glycerin, sorbitol, and poly-ethylene glycol. The series cannot be extended too far, however, since theether linkages tend to reduce hygroscopicity. The \"strength\" of a humectant

Humectants in Personal Care Formulation 101is principally dependent on the ratio of hydroxy groups to carbons. As this ratioincreases, there is an increase in the hygroscopicity.1. GlycerinChemically, glycerin is a trihydric alcohol denoted as 1,2,3-propanetriol. It isa clear, colorless, viscous material which is miscible in water and alcohol. It isa sweet-tasting, naturally occurring compound which is a component of thou-sands of materials including animal fats and vegetable oils. Today, glycerin is manufactured chiefly from fats and oils that have beenhydrolyzed, transesterified, or saponified. The glycerin that is recovered is inthe crude state and undergoes further \"purification\" through distillation or byan ion-exchange process. Glycerin isalso synthesized from propylene. Fats andoils that are tallow- and vegetable-derived (from coconut oil or palm kerneloil) are both used with about equal availability. Trends toward more use ofnatural products have caused more manufacturers to produce vegetable-de-rived glycerin. While there are many grade or purities of glycerin, the chiefones used in personal care formulation are > 95% purity and usually 99%.These amounts are based on the pure glycerol content of the material (8). As an aside, the spelling \"glycerin\" is commonly used in the United Statesand is interchangeable with the spelling \"glycerine.\" In Europe, this materialis referred to as \"glycerol\" because that is the active material in glycerin. Since glycerin has three hydroxyl groups, a number of analogs may beformed. Like most other alcohols, glycerin can form esters, amines, and alde-hydes. It has two primary hydrxyl groups and one secondary hydroxyl group.The primary hydroxyls tend to react before the secondary hydroxyl, and thefirst primary hydroxyl before the second primary hydroxyl. In any reaction,however, the second primary hydroxyll and the secondary hydroxyl will reactto some extent before all the reactive groups have been used (9). This accountsfor the distribution seen in materials such as glyceryl monostearate, in whichthere typically is about 70% mono-, 20% di-, and 10% triester. While glycerinis stable to atmospheric oxidation under normal conditions, it can be oxidizedby other oxidants. Chief among the advantages of glycerin in personal care products is that itexhibits good equilibrium hygroscopicity and is virtually nontoxic except atvery high concentrations, where a dehydration effect on the skin can be seen.At low temperatures, glycerin tends to supercool rather than crystallize. It

102 Gessleindoes not discolor nor produce off odors with aging. It is a good dispersing agentfor pigments in foundation makeups, and lowers the freezing point of lotionsand shampoos effectively, which helps maintain clarity of the systems andhelps prevent bottle cracking due to freezing. The principal drawback of glycerin is that it can produce stickiness increams or lotions. This can be overcome by adjusting its use level or by usingit in combination with another humectant such as sorbitol.2. Propylene GlycolPropylene glycol is the second most widely used humectant in personal careformulations. It is a three-carbon molecule with two hydroxyl groups. It is aclear, colorless, viscous liquid and, like glycerin, is miscible in water. The safetyof propylene glycol is well known, and ingestion is harmless because in thebody its oxidation results in metabolically useful pyruvic and acetic acids (10). Propylene glycol is obtained from propylene by the cracking of propane.The propylene is converted to the chlorhydrin with chlorine water. Thechlorhydrin is then converted to the glycol with a sodium carbonate solution.Propylene glycol can also be obtained from the heating of glycerin in the pres-ence of sodium hydroxide (11). The chief advantages of propylene glycol in personal care formulations isthat it is less expensive than glycerin and has a better skin feel when used increams and lotions. It is also a somewhat better coupling agent or co-solventthan is glycerin for fragrance oils. Propylene glycol effectively reduces the\"balling up\" of oil-in-water creams, giving a better rub-out. Additionally, it hassome antimicrobial activity and will enhance the activity of antimicrobial agents.Some disadvantages of propylene glycol are that it is not \"naturally\" derivedand it tends to de-foam surfactant systems. It also greatly reduces the viscosityof personal care preparations.3. Sorbitol I

Humectants in Personal Care Formulation 103Sorbitol is a hexahydric alcohol which is typically supplied as a 70%-by-weightsyrup, although the crystalline form is also available from analytical-reagentsuppliers. It was first discovered as a component of the ripe berries of themountain ash. Commercially, it is obtained by the high-pressure hydrogena-tion of glucose or by electroreduction. Sorbitol exhibits the best dynamic hygroscopicity of the humectants, al-though it has somewhat lower equilibrium hygroscopicity than other materials.The skin feel of sorbitol is soft and nongreasy, with very little tackiness. Thismakes the use of sorbitol as an emollient possible, especially in systems wherethere is a high-viscosity and heavier body. It is often used as a cost-effectivesubstitute for glycerin in creams and lotions. Sorbitol is not used as an \"anti-freeze\" in personal care formulations, as glycerin and propylene glycol are. An interesting property of sorbitol is that it has the ability to chelate iron,copper, and aluminum ions. It is most effective at alkaline pH and in highly acidicmedia. Sorbitol has little chelation ability at neutral pH. This may be importantin cleansing systems where there is concern about high iron content in water.4. 1,3-Butylene GlycolLike many of the humectants described, butylene glycol is a clear, viscous li-quid. It contains two hydroxyl groups and has a slightly sweet taste. Productionof butylene glycol is achieved by the catalytic hydrogenation of acetaldehyde.This material is further distilled and purified to produce a food-grade quality. 1,3-Butylene glycol is a material that has become more important in recentyears, primarily because of its reported hypoallergenicity. It has a hygroscopic-ity about that of propylene glycol and acts as an effective antifreeze in liquidsystems. Butylene glycol is a more effective essential oil and fragrance solubilizerthan either glycerin or propylene glycol. This is especially true for the citrisesand mint oils, for which 1,3-butylene glycol acts as a very effective co-solvent.It also helps retard the loss of fragrance through plastic packaging. As an anti-microbial adjunct, butylene glycol acts to enhance the distribution of preservativesacross the water/oil interface better than either propylene glycol or glycerin.5. Polyethylene Glycols Where n = 2 through 90,000A whole range of polyethylene glycols is available to the personal care formu-lator, from a PEG number average molecular of about 200 to well over 6000.

104 GessleinIt is only the shorter polyethylene glycols of about PEG numbers 200 through2000 that exhibit any real hygroscopicity. As the PEG number increases, thewater solubility and humectancy decrease. As an example, PEG-200 is com-pletely water-soluble and has a hygroscopicity of about 70% of that of glycerin,while a PEG-1000 is only about 70% soluble in water and has a hygroscopicityof the Older of 35% that of glycerin. At a PEG number of 4000 the material isonly about 60% soluble in water and is nonhygroscopic. The physical forms of the polyethylene glycols range from a liquid througha hard flake, again dependent on the PEG number. The higher the PEGnumber, the more solid is the material. While the higher polyethylene glycolsare not humectants, they may be used as very effective thickeners for water-based systems, especially systems that have high surfactant loading. When theyare used in this manner, it is necessary to balance the viscosity desired with thehand feel of the system since the very high polyethylene glycols tend to leavea \"greasy\" feel on the skin. Often the higher polyethylene glycols are used inconjunction with glycerin or sorbitol to improve humectancy and hand feel. Polyethylene glycols of up to about 2000 PEG numbers are often used increams and lotions to prevent rolling or balling of the cream upon application.These shorter PEG numbers have a smooth, lubriciousness feel on the skin. Insome brushless shave creams they are used to replace all or part of the normalemollient system and improve wash-off. Polyethylene glycols are toxicologicallyinert, as exemplified by their use in a USP PEG ointment. This is a 1:1 mixtureof PEG-400 and PEG-4000 and is used as a water-washable ointment.6. Sodium Pyrrolidone Carboxylate (Na-PCA)Sodium PGA is the salt of pyrrolidonecarboxylic acid and is found naturally inhuman skin. It is typically available as a 50% active aqueous solution. Whenplaced on the skin, it has virtually no skin feel and, due to its salt nature, isobviously entirely soluble in water. In the so-called natural moisturizing factor(NMF), a theoretical collection of compounds that are thought to be presentin the skin and responsible for ubiquitous moisturization, sodium PCA com-prises about 10-15% by weight (12). Sodium PCA is a highly effective humectant that is applicable for use in allnormal creams, lotions, and surfactant-based cleansing products. It has excel-lent humectancy, showing a moisture-binding capacity 1.5 times greater thanglycerin, twice as great as propylene glycol and six times that of sorbitol (13).Its dynamic hygroscopicity is somewhat less than sorbitol and about equal tothat of glycerin. These characteristics make it one of the best humectants to

Humectants In Personal Care Formulation 105use for skin-softening effects. Unlike other humectants discussed, it has noreported effect on preservative systems and no effect as a co-solvent for solu-bilizing essential oils. One of the prohibiting factors to widespread use of thismaterial is its relatively high cost compared to other humectants.7. Acetamide MEAAcetamide MEA is the aliphatic amide of acetic acid and monoethanolamine.It has very good toxicological properties, with a primary eye irritation index, askin irritation index of zero, and an LD50 of >24 g/kg. As presented, to thepersonal care formulator, it is a clear liquid with a yellow cast that has a slightacetic acid odor. It is typically available as a 70% active aqueous solution. Acetamide MEA offers a number of useful properties to the personal careformulator. Incorporation of acetamide MEA in a shampoo has been shownto reduce eye irritation (14). It normally has little effect on the viscosity in thesesystems while offering good hygroscopicity. Acetamide MEA is a good dye/pigment-dispersing agent that allows for the easy incorporation of these ma-terials into makeups and affords their even deposition upon application.8. Miscellaneous \"Humectants\"Many materials have been claimed to be humectants based on their water-absorbing characteristics when evaluated empirically. Among the many arethe collagens, both tropocollagen and the hydrolysates, the keratins, glucoseethers and esters, and various mixtures of materials of botanical nature. In1980 Deshpande, Ward, Kennon, and Cutie published work done in evaluat-ing these humectants against the known classical materials such as glycerinand sodium lactate (15). In these studies, materials were evaluated in vitro atseveral humidity conditions ranging from a relative humidity of 20% to one of90%. At all humidity conditions, the proteins and derivative exhibited poorresults and in fact, at relative humidities of 79% or below, they had negativeresults. The glucose ethers and esters gave good results, as did the lactates andlactylates. It must be noted that at 20% relative humidity, no humectant wasfound to be effective in this study. In in-vivo human studies conducted in the Henkel COSPHA USA AWTLaboratories, some interesting results were found (16). Using a dermal pha-sometiy technique, several wheat proteins and their hydrolysates were con-trasted with collagen and collagen hydrolysates. In these studies it was foundthat a 1.5% active wheat protein increased the moisturization of the skin by20%. Collagen produced similar results. The hydrolysates of both wheat andcollagen had little effect on moisturization of the skin,

106 GessleinTable 1 Classic Skin Care Formulations Percent in formulations 12 3 4 5Mineral oil 15.0 10.0 — — —Isopropyl palmitate 5.0 — 3.0 — — 2.0Cetearyl alcohol 2.0 1.0 1.5 3.0 3.0 12.0Dicapryl ether — 3.0 — 5.0 — 0.5Coco glycerides — 2.0 10.0 10.0 2.0 qsStearic acid 2.0 1.5 — — — —Glyceryl monostearate 0.5 0.5 0.5 —Ceteareth-20 — 0.5 2.0 1.5Deionized water qs qs qs qsGlycerin 5.0 — 3.0 —Propylene glycol — 3.0 — —VIII. APPLICATION OF HUMECTANTSA. Skin Creams and Lotions Using HumectantsHumectants are used in creams and lotions at levels of 1-5% typically to pre-vent surface dehydration of the product when exposed to air. In some creams,glycerin is used at a 10% loading to enhance the moisturization/remoisturiza-tion of the skin. Glycerin was traditionally used as an \"active\" ingredient inhand and body creams because it tended to reduce roughness, which is duepredominantly to the dehydration of the uppermost levels of the stratum cor-neum. Some classic skin care formulations are given in Table 1. In experiments conducted by Griffin, Behrens, and Cross and confirmed byBryce and Sugden (17), it was determined that the amount of humectant toreach equilibrium at 70-75% relative humidity was about a 65% humectantsolution. In the same work it was determined that at 40-60% relative humidity,equilibrium would be reached using a 85% humectant solution. Obviously,these are impossible amounts for normal personal care formulation. Bryce andSturgen reported not only maxima but also minima. In this work it was foundthat as little as 1% humectant produced some effect. According to this, itseems that the normal use levels of 1-5% humectant in a cream or lotion is areasonable compromise between maximum hygroscopicity and other desir-able properties of the formulation. Other investigators have found that certain combinations of humectantsfunction more effectively in skin creams than when the humectants are usedalone (18). For example, it has been claimed that when a mixture of glycerin,

Humectants in Personal Care Formulation 107Table 2 Classic Cleansing Formulations Percent in formuladons 12Hair care 28.0 14.0 Ammonium lauryl sulfate — 14.0 5.0 3.0 Sodium lauryl sulfate 7,5 5.0 Cocamide DEA 5.0 3.0 Cocamidopropyl betaine qs qs pH6.5 pH6.5 Glycerin Deionized water 20.0 35.0 Citric acid 20.0 —Body cleansing 5.0 6.0 Ammonium lauryl sulfate 2.5 3.0 Sodium lauryl sulfate 3.0 5.0 Cocamidopropyl betaine 2.0 — Cocamide DEA qs qs Glycerin pH6.0 pH6.0 Sorbitol Deionized water Citric acidsodium lactate, urea, and collagen are incorporated into a formula, they sig-nificantly improve the suppleness of skin. The humectants normally used are of the organic class (glycerin, propyleneglycol, sorbitol, 1,3-butylene glycol), and to a lesser extent the metal-organicclass (sodium PCA, sodium lactate). Attention must be paid to the use level,since it has been reported that these humectants can actually remove moisturefrom the skin at very high levels and cause burning. The addition of humectants to stearic acid-based creams with high stearicacid contents can reduce the problem of flaking. Sorbitol is probably the bestin this regard, followed by propylene glycol and glycerin. Glycerin can, how-ever, leave a stickiness to the skin after the emulsion has been applied andallowed to dry or \"absorb.\" Sorbitol normally produces a soft, velvety feel,while propylene glycol is somewhere between glycerin and sorbitol.B. Hair Applications for HumectantsHumectants are typically added to shampoos, body washes, and bath andshower gels at 2-5% by weight to prevent a surface skin from forming on theproduct. They also help to reduce the cloud point of the product, ensuring

108 Gessleinclarity in cold temperatures, and help to prevent package cracking. It must benoted that while there are beneficial effects from humectants in these appli-cations, care must be used with regard to the amounts used. Humectantstend to reduce the foaming of surfactant systems. Since most consumers relatefoaming with cleansing efficacy, any material that \"de-foams\" must be usedjudiciously. Some classic cleansing formulations are listed in Table 2. The idea has been propagated that the addition of humectants to a sham-poo helps to moisturize the hair shaft. Aside from large, very hygroscopic poly-mers, it is debatable whether any humectant remains on the hair shaft aftershampooing and rinsing. The situation is different, however, with regard toleave-on conditioners, where the humectant will form a very thin film thathelps to bind water to the hair shaft. Since the conditioner is of the leave-ontype, the humectant film stays in place until it is washed or rinsed out of thehair. Newell describes how a humectant-containing hair treatment can help torestore moisture to severely damaged hair (19).IX. FUTUREHumectants will continue to have a place in personal care formulation for thereasons described above. In the near future, more \"natural\" humectants willbe used over the synthetics. There is also a trend toward the use of polymerichumectants that are not based on ethylene oxide. These materials will offerthe lasting power associated with polymers and still be very mild to the skinand eyes. Humectants are continually finding more applications in personalcare products. This makes it important for the formulator to stay current withthe latest technology.REFERENCES 1. Balsam MS. Cosmetics Science and Technology. New York: Wiley-Interscience, 1972:198. 2. Jungermann E, Sonntag N, eds. Glycerine: A Key Cosmetic Ingredient. New York: Marcel Dekker, 1991:9. 3. Balsam MS, Sagarin E. Cosmetics Science and Technology. New York: Wiley-In- terscience, 1972:198. 4. Budavari S, ed. The Merck Index. Rahway, NJ: Merck, 1989:1375-1376. 5. Humectants. In: Harry's Cosmeticology. New York: Chemical Publishing, 1982: 641. 6. Weast R, ed. CRC Handbook of Chemistry and Physics. Boca Raton, FL: CRC Press, 1981. 7. Humectants. In; Harry's Cosmedcology. New York: Chemical Publishing, 1982: 642. 8. Henkel Corp. Glycerine: An Overview. Ambler, PA: Henkel.

Humectants In Personal Care Formulation 109 9. Pfiser & Pfiser. Advanced Organic Chemistry.10. Budavari S, ed. The Merck Index. Rahway, NJ: Merck, 1989:1247.11. Ibid.12. Ajidew. N-50. Ajinomoto Corp.13. Takahashi M, et al. A New Method to Evaluate the Softening Effect of Cosmetic Ingredients on the Skin. J Soc Cosmet Chem 19??; 35:171nnnl81.14. Shercomid AME-70 Technical Bulletin. Clifton, NJ: Scher Chemicals, July 1977.15. 1980 Deshpande, Ward, Kennon, and Cutie published16. Henkel Cospha USA AWT Laboratories.17. Bryce and Sugden. J Pharm 1959.18. Jungermann E, Sonntag N, eds. Glycerine: A Key Cosmetic Ingredient. New York: Marcel Dekker, 1991:346.19. Newell GP. Method of restoring normal moisture level of hair with severe moisture deficiency. U.S. Patent 4,220,166 (1980).

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6Emollient Esters and OilsJohn Carson and Kevin F. GallagherCroda, Inc., Edison, New JerseyI. INTRODUCTIONThis chapter will provide an introduction and survey of emollient esters andoils as they are encountered in personal care formulations. The purpose ofproviding this information is to create a conceptual \"road map\" which can beused by formulators to distinguish among the performance properties of alarge class of ingredients, by relating their performance properties to thechemical and physical characteristics of the ingredients themselves. According to the Oxford English Dictionary the definition of the adjectiveemollient is: \"that which has the power of softening or relaxing the living ani-mal textures,\" It is derived from the Latin verb mollire, meaning \"to soften.\" While a dictionary definition is helpful, it may be more useful to see howvarious industry authors have defined an emollient. Strianse (1) defined anemollient as \"an agent which, when applied to a dry or inflexible corneum, willaffect a softening of that tissue by inducing rehydration.\" The implication hereis that esters and oils would induce rehydration by reducing the loss of waterfrom the stratum corneum (typically measured by the transepidermal waterloss, or TEWL). More recently, Idson has attempted to clarify the differencebetween a moisturizer and an emollient. His argument bears repeating:\"There are only two cosmetic ways to treat a dry skin condition: either byattempting to hydrate it with externally applied water-miscible agents or bylubricating and occluding the skin with water insoluble materials. By usage,the former have come to be called moisturizers and the latter emollients orconditioners.\" 111

112 Carson and Gallagher Since this is a broad class of ingredients which also includes triglycerideoils, the use of these compounds dates back to the earliest use of topicallyapplied natural materials to effect some changes in the condition of skin orhair. As is the case with many other types of formulation components, thehistory of this class of materials has developed from the initial use of naturallyoccurring ingredients through the development of synthetic compounds thatpossess improved performance characteristics. In fact, the well-known coldcream formula of Galen (3) from the second century employed almond oil asthe emollient. Vegetable oils were the predominant emollients up until the late 19th cen-tury, when mineral oil and petrolatum became commercially available as prod-ucts of petroleum oil distillation. Other emollients, like lanolin and hydrogen-ated vegetable oils, became commercially available in the early part of the 20thcentury. The development and availability of synthetic esters occurred duringthe 1930s and 1940s. Many of these esters were spinoffs from the developmentof synthetic lubricants (4) and so paralleled the intense military activity of thisperiod.II. NATURALLY OCCURRING ESTERSAlthough these materials were the first used, they are still in wide use todaybecause they perform so well. One of the driving forces in their continuedpopularity is the fact that these materials most closely mimic the lipid compo-nents which occur naturally in skin and hair, and are largely responsible for itscondition.A. TriglyceridesTriglycerides compose the largest group of oils and fats found in both vegeta-ble and animal sources. Triglycerides are compounds in which three fatty acidradicals are united by oxygen (in an ester linkage) to glycerine. A samplechemical structure is shown in Figure 1. Since triglycerides occur naturally, wedo not typically describe their biochemical synthesis. We do, however, need tobe familiar with the breakdown reaction by hydrolysis, since these productsinclude fatty acids and glycerine, and fatty acids are important components forthe manufacture of synthetic esters, which will be described in later sections.The alkaline hydrolysis of triglycerides is typically carried out in the presenceof water and is known as \"fat splitting.\" A simplified description is providedin Figure 2. The most important differentiating characteristic among the triglyceridesis their fatty acid composition or \"distribution.\" It is the component fattyacids which will contribute the particular properties which we associate with

Emollient Esters and Oils 113Figure 1 Triglyceride structure. R, R', and R\" represent hydrocarbon chains in whichthe number of carbon atoms in the chain typically ranges from 7 to 21 and most com-monly from 11 to 17.triglycerides (Table 1). For instance, Tristearin is the triglyceride composedentirely of stearic acid . Its meling point is 69 to 70°C, andit is solid at room temperature. Triolein is the triglyceride composed entirely of oleic acid . It has a solidification point of 4°C, and it is liquid at room BaseTryglyceride Mixture of fatty acid soaps (a Fat)Mixture of fetty fixture of Saltacid soaps fatty acidsFigure 2 Alkaline hydrolysis (saponification) of triglycerides.

114 Carson and GallagherTable 1 Melting Points of Some Fatty Acids and TriglyceridesName Carbons MP acid (°C) MP triglyceride (°C)Saturated 8 16.7 8.3 Caprylic 10 31.6 31.5 12 44.2 46.4 Capric 14 54.4 57.0 Laurie 16 62.9 63.5 Myristic 18 69.6 73.1 20 75.4 na' Palmitic 22 80.0 na Stearic Arachidic 18:1 cis 16.3 5.5 Behenic 18:1 trans 43.7 42.0Unsaturated 18:2 cis -6,5 -13.1 Oleic 18:3 cis -12,8 -24.2 Elaidic 22:1 cis 33,4 30 Linoleic Linolenic ErucicNot available.temperature. Neither Tristearin or Triolein occurs naturally, but one can eas-ily see how the physical form of a triglyceride could be deduced from its fattyacid distribution. The authoritative source for information about triglyceridesand their fatty acid distributions is Bailey's Oils, Fats & Waxes (5).1. Vegetable TriglyceridesVegetable triglycerides, such as olive oil, were probably the original emol-lients. In general, vegetable triglycerides are called oils, whereas animal tri-glycerides are more commonly referred to as fats. This nomenclature aloneprovides a key to their respective physical forms and fatty acid distributions. Vegetable oils are more likely to be fluid at room temperature. This fluidityis conferred by the composition and nature of their component fatty acids.Vegetable oils typically contain a higher proportion of unsaturated fatty acidtriglyceride esters than animal fats. These unsaturated fatty acid esters containat least one carbon-to-carbon double bond, so they are not \"saturated\" withhydrogen. The presence of this double bond creates a kink in the fatty chain.This kink, or bend, will make it more difficult for the molecule to form anordered structure, which is necessary for solidification. A simple comparisonbetween a saturated fatty acid, stearic acid, and an almost identical (but fortwo hydrogen atoms) unsaturated fatty acid, oleic acid, is shown in Figure 3. Both the nature of the fatty acid distribution and the degree of fatty acidunsaturation are important concepts which will recur in our attempts to

Emollient Esters and Oils 115 Stearic acid Oleic acidFigure 3 Structures of stearic and oleic acid.understand the relationship between the structure and the function of esters,including the synthetic esters we will encounter later. Since vegetable oils are more likely to be fluid at room temperature, owingto their unsaturated fatty acid ester distribution, they have played a more im-portant role as emollients. Clearly, a fluid material is more likely to be able to\"soften\" than a solid. Vegetable oils, such as olive oil, have long been used tosoften the skin. This use predates the use of emulsions. In fact, one could viewthe development of the emulsion as the invention of a more aesthetically pleas-ing and efficacious way of applying vegetable oils to the skin! Unfortunately, vegetable oils are not the perfect emollients. This is whytheir use was supplanted first by mineral oils, and more recently by syntheticesters. The advantage of fluidity and hence softening properties that is con-veyed by the presence of unsaturated fatty acids in the triglyceride is balancedby the disadvantages conferred by these same unsaturates. The chief disad-vantage is the lack of stability of the unsaturates, due to the susceptibility ofthe carbon to carbon double bond to chemical attack, especially by oxidation. This oxidation of such double bonds is commonly referred to as rancidity,and it produces the unpleasant odor and taste that accompany these chemicalchanges. Clearly, this means that where vegetable oils are used, it is importantto use antioxidants to avoid the unpleasant effects of rancidity. Another disadvantage of the use of vegetable oils is their aesthetic (\"feel\")properties. While vegetable oils are certainly capable of softening the skin,they do so while contributing an oily feel to the final formulation, such as anemulsion. This is due in part to the nature and size of the triglyceride molecule.It contains three fatty chains, and this large proportion of fatty component nodoubt contributes to the oily feel of the material.

116 Carson and Gallagher The relatively large size of the triglyceride molecule is also a disadvantagefrom the standpoint of emulsification, since it is easier to emulsify a smallermolecule. In general, emulsification is somewhat easier when the emulsifier islarger than the compound to be emulsified. Before leaving the subject of vegetable oils, it is important to include somebrief mention of trace components. These trace components are nontriglyc-eride in nature and are often described as unsaponifiables, since they will notsaponify in the presence of caustic to yield a fatty acid soap. Most often theseunsaponifiables consist of sterols, or other hydroxyl containing compounds.Some of these polar compounds can have beneficial properties, such as thesterol fraction on avocado oil (5). The secondary products of oxidation can also be present in trace quantities,depending upon the components of the oil, its oxidation, and the stability andstorage history of the triglyceride. These secondary oxidation products includealdehydes and ketones, which can act as potential irritants, or further catalyzeoxidative degradation. Recent advances in chromatographic purifications (6)have made possible the production of highly purified triglycerides that arevirtually free of such components. The information in Table 2 provide thecomparative fatty acid distribution for a number of well-known and less wellknown triglyceride oils.Table 2 Fatty Acid Composition of Several Plant-Sourced Triglyceride Oils Composition wt% of fatty acidsName Laurie Myristic Palmitic Stearic Oleic Linoleic Linolenic (Cl2:0) (Ci4:o) (Cl6:0) (C,8,0) (C,8.l) (Cl8:2) (C,8:3)Almond — 7 66 27Apricot kernel —— 5 — 62 33 —Avocado — 11 3 — 69 15 —Coconut' 48 16 10 27 — —Evening primrose — — 6 2 9 68 15Olive — — 12 2 75 10 —Peanut — — 8 4 62 20 —Saflower — — 5 4 13 76 —Sesame — — 8 5 40 47 —Soybean — — 11 4 25 54 6Sunflower — — 4 2 29 60 —Wheatgerm — — 13 3 14 58 8Contains 7% capiylic acid (C8:o) and 8% capric add (Cio:o)-

Emollient Esters and Oils 1172. Animal TriglyceridesThe same concepts that are important for the vegetable triglycerides are alsoof importance in understanding animal and marine triglycerides. These con-cepts are mostly related to the fatty acid distribution of the oils or fats and canbe summarized as follows: 1. Hydrocarbon chain length of component fatty acids 2. Degree of unsaturation of the component fatty acids 3. Presence of trace or minor componentsIt is these properties that will determine the physical form of the oil or fat, aswell as its feel on the skin and stability. Animal oils or fats originate from a wide variety of animals and parts ofanimals. Most animal fats come from the subcutaneous fat layer. Examplesinclude beef tallow and lard. Due to a higher content of saturated fatty acid-containing triglycerides, these materials are typically soft solids rather thanfluid oils. An exception would be mink oil, where the subcutaneous fat is \"win-terized\" (essentially chilled and filtered) to remove the more saturated com-ponents. This process provides an \"oil\" of animal origin containing a higherpercentage of triglycerides containing palmitic oleic acid esters. Animal oils can be from sources other than subcutaneous fat. Egg oil andmilk (butter) fat are good examples. Table 3 provides some composition information on a variety of animal fatsand oils. It may be useful to remember that although animal fats are not typi-cally used directly as emollients, they can be used as a source of fatty acids forthe production of synthetic esters.Table 3 Fatty Acid Distribution of Some Animal- and Marine-Sourced Triglyceride Oils Composition wt% of fatty iicidsName Myristic Palmitic Palmitoleic Stearic Oleic Linoleic EPA DHA (Cl4:0) (Ci6:o) (Cl6:l) (Cl8:0) (C,8:l) (CiS:2) (C20:5) (C22:6)Menhaden 11 19 10 3 15 1 11 8Mink 4 16 18 2 42 18 — —Orange 11 12 — 56 2 ——roughyShark liver' 2 12 7 4 30 6 — 10Tallow 4 28 5 23\" 38\" 2 — —Lard 2 24 3 13 44 9 — —Milkfats\" 10 30 4 11 25 2 — —^Shark liver oil contains 5% linolenic acid.\"Extremely variable amounts; these are average values of wide ranges.\"Contains significant amounts of lower fatty acids (~15%).

118 Carson and Gallagher3. Marine OilsThe marine oils are an interesting third class of triglycerides since they havevalue not only for their physicochemical properties as emollients, but also fortheir potential in aiding the biological functioning of the skin. This potentialfor biological activity is especially present in the highly polyunsaturated oilsfrom cold-water fish, such as salmon, anchovy, and menhaden. Although a full description of the biological activity of these polyunsatu-rated fatty acid (PUFA) containing triglyceride oils is beyond the scope of thischapter, some brief description of these oils and their component fatty acidsmay be useful as an introduction to the subject. Cold-water fish, like thosementioned above, are rich in triglyceride content. These triglycerides containtwo very important PUFAs: eicosapentaenoic acid (EPA), and docosahexa-enoic acid (DHA). Their structures are shown in Figure 4. Both EPA (Czois) and DHA (0:2:6) play an important role in human nutri-tion and biophysiology because they are precursors to prostaglandins, a classof biologically active compounds which help to control a variety of metabolicfunctions. Prostaglandins are made in the \"arachidonic acid cascade.\" Thereare a number of sources of valuable information concerning the metabolismof these fatty acids. Marine oil use in topical systems has been limited due to their extremesensitivity to oxidation, by virtue of their highly unsaturated nature. The tri-glycerides also represent a serious formulating challenge since most marineoils have a \"fishy\" odor. In addition, as these oils oxidize (rancidify), they be-come increasingly malodorous, with a more paintlike smell. CH3EPA \"CH3DHAFigure 4 Structures of eicosapentaenoic and docosahexaenoic acids.

Emollient Esters and Oils 119B. Lanolin and Lanolin DerivativesUnlike triglycerides, where the alcohol fraction of the ester is glycerin, thealcohol fraction of the naturally occurring esters that comprise lanolin are verydiverse. This alcohol fraction can be divided into two large classes of com-pounds: the aliphatic alcohols and the steroidal alcohols. Examples of thestructures of these materials are shown in Figure 5 and Table 4. These variousalcohols are present in their esterified form. The fatty acid portion of the estersalso presents a diverse range, as described in Table 5. Lanolin can be described as the purified form of wool wax, or wool grease.This is a naturally occurring lipid present in the fleece of sheep and typicallyobtained during the \"scouring\" of the wool to clean it prior to further process-ing. This lipid consists of a complex mixture of esters whose acid and alcoholfractions have been described in the previous figure and tables. Lanolin has a long history of use as an emollient in cosmetics and pharma-ceuticals; its first use dates to ancient times. Lanolin is a soft, tenacious solidwith a melting point of approximately 40°C. Besides being useful as an emol-lient, lanolin has some beneficial properties as an auxiliary emulsifying agentCholesterol LanosterolC27H46O CsoHsoO Dihydrolanosterol C30HS2OFigure 5 Structures of cholesterol, lanosterol, and dihydrolanosterol.

120 Carson and GallagherTable 4 Alcoholic Constituents of Wool Wax or Lanolin Approximate %Constituents 4 6Aliphatics n-alcohols: 7 members, octadecanol to triaceontanol 7 iso-alcohols: 5 members, 16-methylheptadecanol to 24-methylpentacosanol 0.5 antewo-alcohols: 6 members, (+) 14-methylhexadecanol to 3 (+) 24-methylhexacosanol n-alkan-l,2-diols: 1 member, hexadecanediol 20 wo-alkan-1,2 diols: 4 members, wo-octadecanediol to 5 isotetracosanediol 2Sterols: 5 members 2 cholesterol 7-oxocholesterol 10 cholestane-3,5,6-triol 10 cholest-7-en-3-ol (and) 1 cholesta-3,5-dien-7-one 4Isocholesterol: 6 members 2 lanostero dihydrolanosterol 1 78 agnosterol 22 dihydroagnosterol 7,ll-dioxolanost-8-en-3-ol (and) 7-oxolanost-8-en-3-olHydrocarbons: number unknown structure unknownTotalUnidentified residueSource: Ref. 6.of the water-in-oil type. The emollient properties of lanolin have been dem-onstrated by a number of workers.1. Lanolin OilLanolin itself can be physically separated into a fluid and a wax fraction. Theresulting fluid fraction is known as lanolin oil. It is more lubricious than lanolinsince it is a viscous fluid and not a soft solid at room temperature. The majoradvantage of lanolin oil is that it is clearly miscible with mineral oil in all pro-portions and does not form a precipitate. Thus, stable \"absorption bases\" com-posed of lanolin oil, lanolin alcohol, and mineral oil can be made which areuseful formulating tools for emulsions.

Emollient Esters and Oils 121Table 5 Acidic Constituents of Wool Wax or Lanolin Approximate %Constituents 7 22n-acids: 9 members 29 decanoic to hexacosanoic 25 3iso-acids: 10 members 86 8-methylnonanoic to 26-methyllieptacosanoic 14anteko-adds: 12 members (+) 6-methyloctanoic acid to (+) 28-methyltriacontanoica-hydroxy-n-acids 2-hydroxydodecanoic to 2-hydroxyoctadecanoica-hydroxy-wo-acids: 1 member 2-hydroxy-16-methylheptadecanoicTotalUnidentified residue (mostly unsaturated acids?)Source: Ref. 6.2. Lanolin DerivativesA number of derivatives can be made from lanolin. Often these derivatives aremade by first saponifying lanolin with sodium hydroxide and water therebyhydrolyzing the lanolin esters into their constituent acids and alcohols. Afterthis, the constituents can be further reacted with a large number of compoundsto alter their properties. Typically, these materials have altered physical formsas well as different solubility characteristics. The resulting esters will be de-scribed, with the other synthetic esters, in the next section.C. Other Natural EstersThe manufacture of esters is one of the more elegant ways that an organismhas to make compounds to protect itself and to store energy.III. SIMPLE ESTERSEmollient esters are made from a wide variety of acids and alcohols. Typicallyat least one of these fractions could be described as fatty in nature, meaningthat it possesses a long hydrocarbon chain which would make that fractionsoluble in oil and insoluble in water. This provides us with one useful way ofcategorizing these esters: namely, according to their constituent acid and al-cohol fractions. Of course these acids and alcohols could also possess more than one func-tional group. We could use polyhydric alcohols, polybasic acids, or hydroxy

122 Carson and Gallagheracids in our synthesis. This differentiation provides us with another organiza-tional system. We can have esters made from one acid and one alcohol (simpleesters) or those made from multifunctional acids or alcohols (complex esters). As in the case of the triglycerides, many of the properties of the syntheticesters are directly related to the nature of the hydrocarbon chain contributedby the fatty acid portion of the molecule. In contrast, however, we now alsoneed to concern ourselves with variations in the hydrocarbon chain of thealcohol fraction, since this will also contribute to the properties of the resultingester. These parameters can be summarized as follows: 1. Hydrocarbon chain length of the component acid and alcohol 2. Degree of unsaturation of the component acid and alcohol 3. Presence of branching in either carbon chain 4. Presence of multiple acid or alcohol fractions 5. Presence of trace or minor components The properties may be better understood if we examine the structure of a\"typical\" synthetic ester and its synthesis route. As an example we'll look atisopropyl myristate (IPM), a well-known ester used in personal care products.IPM is manufactured by combining isopropyl alcohol (IPA) and myristic acid.Typically this is done in the presence of an acid catalyst under conditions wherethe water produced by the esterification can be removed to allow the reactionto continue to completion. Figure 6 provides an illustration of this reaction. Inthis case, isopropyl alcohol quantities in excess of the stoichiometric amountneeded for the reaction are frequently used since some IPA is removed withthe water from the reaction. Isopropyl MyristateFigure 6 Reaction of isopropyl alcohol and myristic acid to produce isopropylmyristate.

Emollient Esters and Oils 123 A brief description of the structural parameters listed above will lead thereader to consider the infinite variety of esters that can be manufactured. For-tunately for the purposes of this review, there is one common characteristic ofall the emollient esters used in personal care. They all possess at least one fattychain (or similar long chain) contributed by either the acid fraction, the alcoholfraction, or both. This means that the fundamental nature of the synthetic esterrevolves around the chemical modification of a fatty chain to achieve a desiredset of properties. Isopropyl myristate is perhaps the best known of the simple esters. We canengage in some reasonable speculation concerning the thought behind its de-velopment, based on our knowledge of the functionality of the triglycerides.The triglycerides, which function as fluid emollients, do so because of thepresence of unsaturated fatty acid esters (typically oleic acid, Cisii) in thetriglyceride. While conferring fluidity and emollience, the oleate chains alsocontribute to the potential for oxidation, and hence instability. In contrast, IPM is a fluid ester that does not rely on the unsaturation ofthe fatty component for its fluidity. Rather, it is due to the branched nature ofthe alcohol component. Branching helps to interrupt the orderly associationof the long straight chain fatty components, which leads to the irregular pack-ing of the molecules and hence fluidity. There are two important lessons to belearned from this: (1) changes in the alcohol fraction can \"substitute\" for vari-ations in the acid fraction, and (2) branching can be a substitution for unsatu-ration with regard to fluidity. In the case of IPM, the branched chain nature of the alcohol \"substi-tutes\" for the lack of unsaturation in the fatty acid portion of the molecule.We might refer to these two lessons as the \"superposition principles\" of esterdevelopment.A. Straight-Chain EstersThis section will discuss the variety of physical properties and emollient estercharacteristics that are obtainable from simple esters made from eitherstraight hydrocarbon chain fatty acid or straight hydrocarbon chain fattyalcohols.1. Acid Component VariationsSince we already have an understanding of the effect of variations in the fattyacid hydrochain for the triglycerides, it may be useful to review this informa-tion since it applies to the synthetic esters as well. As we increase the hydro-carbon chain length of the fatty acid, keeping the alcohol portion the same, weincrease the melting point of the resulting ester. At the same time, we decreasethe fluidity and increase the hydrophobicity. This will typically result in an

124 Carson and Gallagheroilier-feeling ester or, if the molecular weight is high enough, an ester with awaxier feel. In our example of the simple ester IPM, we treated it like a single chemicalentity. It must be stressed that this is typically not the case for cosmetic ingre-dients. Usually, an ester like IPM consists of isopropyl esters of a variety offatty acids. IPM consists mainly, but not exclusively, of isopropyl esters myristicacid. Also present, depending on the fatty acid distribution of the startingmaterial, will be quantities of isopropyl laurate, palmitate, and stearate. Thisfact is often overlooked in the comparisons of emollient esters since thesecomparisons are most often performed on the commercially available materi-als. Such comparisons are practically useful, but they often are filled with am-biguity, or at the least imprecision, when they are used for the scientific pur-pose of relating the structure of the ester to performance. We need to keepthese limitations in mind when reviewing such information. These limitations,however, do not prevent us from making useful generalizations or interpreta-tions based upon our understanding of the individual components. The straight-chain, saturated fatty acids typically used in simple emollientesters range from lauric (Cizio) acid to stearic (Ci8:o) acid. Shorter hydrocarbonchains are not capable of delivering the nongreasy, lubricating emollient feelassociated with cosmetic esters. Higher hydrocarbon chains are likely to pro-duce esters with melting points well above skin temperature. It is difficult toconsider these esters as emollients; they are probably better categorized as waxesters. Of course, the simple esters can also be based on unsaturated fatty acidssuch as oleic (Cis:i) and linoleic (Cisa) acids, as well as the less common palmi-toleic (Ci6:i) acid. Although specific comparative data for the isopropyl esters are not com-plete, based on the information available we can make some generalizationsconcerning these straight-chain fatty chains. As the molecular weight of theisopropyl esters increases, so do the solidification or melt point, viscosity, sur-face tension, and amount of ester that persists on the skin after 1 or 2 hours(Table 6). With regard to the correlation of the skin feel of these esters in formulationsto their chemical structure, the \"Rosetta Stone\" of such information is still theGoldemberg Article. In this paper, various esters are compared for their \"in-itial slip\" and \"end feel\" in a simple oil-in-water emulsion. Goldemberg notesthat the isopropyl esters were often ranked the best in each series of estersstudied. The data suggest that although the feel properties of the myristateand palmitate are very similar, the myristate scored slightly higher in initialslip but slightly lower in end feel. Perhaps the most interesting observation isthat the isopropyl linoleate (Cisa) ester is significantly poorer for both initialslip and end feel. Perhaps this is why the saturated-chain and branched-chainisopropyl esters have been preferred in actual use.

Emollient Esters and oils 125Table 6 Some Physical Data for Isopropyl Alcohol EstersFatty acid MP fC) BP (°C)Acetic -73.4 90Butyric — 130-1Caprylic — 93.8Capric — 121Laurie — 196,117Myristic — 192.6,140.2,167Palmitic 13-14 160Stearic 28 207Oleic 223-4 Woodruff, in a more recent review of cosmetic esters, classifies all estersinto three categories: (1) protective emollients, (2) nonocclusive emollients,and (3) dry and astringent emollients. Except for isopropyl isostearate, whichis described as a protective emollient, the remaining isopropyl esters are de-scribed under the dry and astringent category. Woodruff's description of thiscategory is that these esters are \"used to reduce the greasy feel of vegetableoils in water in emulsions.\" Briefly let us now consider the situation of esters of lower-molecular-weightalcohols. The methyl esters of fatty acids are certainly well-known compounds,but are not known as cosmetic ingredients. This could be because the hydroly-sis products include methanol, which could cause irritation and could be toxic. Ethyl esters are also well known compounds, but again, not as cosmeticingredients. Ethyl oleate is used as a topical pharmaceutical agent, to enhancethe skin penetration of lipophilic active ingredients. A pharmaceutical mono-graph exists describing the use of ethyl oleate for this purpose. Perhaps theenhanced skin penetration conferred by the unsaturated oleate is the reasonthe isopropyl esters of unsaturated acids (i.e., isopropyl linoleate) performpoorly in Goldemberg's subjective feel tests. They may penetrate into the skinand not remain at or near the surface to produce a subjective effect. Since physiochemical data exist for the ethyl esters in the pure forms, it maybe worthwhile for us to consider the variation in physiochemical propertieswith changes in the fatty acid component of the ester. These data are sum-marized in Table 7. It is worthwhile to point out the increase in meltingpoint (MP) with the increase in carbon chain length of the fatty acid. Theboiling point (BP) also increases with increasing molecular weight. As pointedout earlier, one of the great advantages of synthetic esters is that we are nolonger limited to using the fatty acids typically found in natural triglycerides.

126 Carson and GallagherTable 7 Some Physical Data for Ethyl Alcohol EstersFatty acid MP (\"C) BP (°C)Acetic -83.6 77Butyric -93.3 120Caprylic -43 208Capric -20 243Laurie 1.8 273Myristic 12.3 295Palmitic a:24, p:19.3 191Stearic 31-3 199Oleic 0.87 207Unoleic — 212In addition to the fatty acids already discussed, we can use fatty acids that arefar outside those occurring naturally—for example, benzoic acid. Examples ofbenzoate esters are illustrated in Figure 7, and some of the physical propertiesare summarized in Table 8. As we would anticipate, we seen an increase in MP and BP with increasingmoelcular weight. Benzoate esters tend to be quite stable both thermally andhydrolytically because they lack aliphatic beta hydrogens and therefore cannotform an enolic structure. Finally, benzoate esters have a very dry, nonoily feel(/ \VC0H +Benmic acid Myristyl alcohol Acid, Heat & Myristyl BenzoateFigure 7 Reaction of benzoic acid with alcohols to produce benzoate esters.

Emollient Esters and Oils 127Table 8 Some Physical Properties of Benzoate EstersFatty alcohol MP (°C) BF (\"C)Ethanol -34.6 213.87Propyl -51.6 211Isopropyl — 218Hexyl 113-117 272Octyl — 305-306Cetyl 30 —on skin and seem to be readily absorbed. Many formulators take advantage ofthis nonoiliness to reduce the oiliere feel of other esters and mineral oil.2. Fatty Alcohol Component VariationsWe began our discussion of simple esters by looking at the effects of variationsin the acid components within the family isopropyl esters since these are pop-pular, well-known cosmetic ingredients. We used them to illustrate how wemight alter the properties of a simple ester by altering the nature of the fattyacid compound. Many of these generalizations will be applicable if we changethe nature of the alcohol fraction of the ester. Since we started with a low-molecular-weight, volatile alcohol (isopropylalcohol), it seems logical to increase the molecular weight of the alcohol frac-tion of the ester and then determine if the generalizations regarding changesin the fatty acid component remain true. Also, we can determine how theproperties of the esters are changed by increasing the molecular weight of thealcohol. Referring to Table 9 one can see the variation in MP and BP caused bychanging the fatty alcohol portion of esters of acetic acid. As is apparent fromthe table, the MP and BP both increase with increasing fatty alcohol hydro-carbon chain lengths. As seen in Table 10, if the acid portion of an ester is small, i.e., formic oracetic acids, there are no dramatic variations in the melting point or boilingpoint of the esters, provided the acid fraction remains relatively small. This isbecause the alcohol fraction is large relative to the acid fraction and is pre-dominantly responsible for the physical properties. This effect becomes moreapparent as the size of the alcohol increases relative to the acid portion. Hydrolytic stability is a major consideration for all esters. Possibly one ofthe reasons for the popularity of the isopropyl alcohol esters of fatty acids inpreference to similar esters that can be made from a low-molecular-weightacid (such as propionic acid) and a fatty alcohol, is their improved hydrolytic

128 Carson and GallagherTable 9 Some Physical Data for Acetic Acid (Acetate) EstersFatty alcohol MP (°C) BP (°C)Isopropyl -73.4 90Propyl -95 101.6Capiylic -38.5 210,112-3Capric -15 244,125.8Laurie 260-270Cetyl a: 18.5;; p: 24.2 220-225Stearyl 34.5 222-223Table 10 Comparison of Some Physical Properties of Acetate,Formate, and Propionate EstersChemical compound MP (°C) BP (°C)Ethyl formate -80.5 54.5Ethyl acetate -83.6 77.06Ethyl propionate -73.9 99,1Hexyl formate -62.6 155.5Hexyl acetate -80.9 171.5Hexyl propionate -57.5 190Octyl formate -39.1 198.8Octyl acetate -38.5 210Octyl propionate ^2.6 228stability. It is important to consider that when an ester such as isopropyl myris-tate does hydrolyze, the resulting products are isopropyl alcohol and myristicacid. However, when an ester such as myristyl propionate hydrolyzes, the re-sulting components are myristyl alcohol and propionic acid. In this example,isopropyl alcohol would have a much more agreeable odor than propionicacid. Additionally, the propionic acid will lower the product pH possibly to apoint where it will be detrimental to the product or consumer. As with fatty acids, one must be careful of the exact chemical makeup of aparticular ester when comparing physical properties, because the raw materi-als are not necessarily pure. The classic example is that of triple-pressed stearicacid which actually contains about 55% palmitic acid and about 45% stearicacid. The chemical composition of the fatty alcohols can vary just as markedly.Typically, stearyl alcohol will contain 65% stearyl alcohol and 35% cetyl alco-hol. Esters made from this fatty alcohol will have the same distribution. Thismeans that the resulting ester will be a mixture. Mixtures will generally have

Emollient Esters and Oils 129properties intermediate between the components. However, occasionally themixtures will have \"eutectic points\" where the melting point of the mixture ismuch lower than that predicted arithmetically. One major factor in the manufacture of esters is the cost of the respectivefatty acids versus fatty alcohols. In most cases we find that the lauric, myristic,palmitic, and stearic fatty acids are significantly cheaper than their counterpartalcohols. This is because the fatty alcohols are usually produced by the reduc-tion of the acid group to an alcohol. Therefore, it is generally less expensiveto produce an ester from a low-molecular-weight alcohol and a fatty acid thanfrom a higher-molecular-weight fatty alcohol and a small acid.3. Modified-Chain AlcoholsUnder the heading of simple esters, we have another type of ester which wasdeveloped to meet several specific needs. One of the needs was economic. Asmentioned above, fatty alcohols can be significantly more expensive than fattyacids. One way to reduce this cost is to react the fatty alcohol with a compoundof lower cost which will maintain the alcohol functionality, yet dilute the cost.Two materials that react in this manner are ethylene oxide and propyleneoxide. Ethyoxylation increases the water solubility of the molecule. Increasing thenumber of moles of ethylene oxide further increases the water solubility. Pro-pylene oxide confers increasing alcohol solubility on the molecule with increasingmoles of propylene oxide. In addition, propylene oxide also confers fluidity byvirtue of the branched methyl group in the propylene oxide repeat unit. When reacted with an acid, ethylene oxide adducts of fatty alcohols producemore polar esters. This is seen in terms of skin feel and adherence, i.e., lubricityenhancing and film-forming effects. If sufficient moles of ethylene oxide areused, the ester becomes water-soluble and functions as a surfactant. In the caseof propylene oxide-modified fatty alcohols, one sees an increase in fluidity anda dramatic lowering of viscosity. Propoxylation can also change the solvencyof the fatty acid esters. These effects can be seen in pigment wetting and intheir ability to dissolve or solubilize other materials. Another effect of alkoxylation is that the molecular weight of the fatty al-cohol is greatly increased. For each repeat unit of ethylene oxide the molecularweight goes up by 44 daltons. The molecular weight goes up by 58 daltons foreach propylene oxide repeat unit. This can produce a dramatic increase in theoverall molecular weight. One of the effects of increasing molecular weightcan be to reduce irritation. Generally, larger molecules are less likely to pene-trate the skin to cause irritation. However, alkoxylation can change the solu-bilizing ability of an ester, making it more soluble in the skin and actuallyenhancing its penetration. Therefore, all esters must be carefully tested todetermine their irritation potential.

130 Carson and Gallagher Ethylene oxide addition can also be used to make \"water-soluble esters.\"These materials are in fact surfactants, as they have both a water-soluble por-tion and an oil- or hydrocarbon-soluble portion. The ethoxylation can becarried out to such a degree that these esters become water-soluble to thepoint where they will actually foam. In use, it is felt that they confer a nonoilytype of emoUiency to a surfactant-based formulation such as a shampoo orbath gel. While these are not truly modified alcohols, let us look at two \"alcohols\"that have been little explored commercially: hydroxy-terminated dimethylpolysiloxanes, and hydroxy-terminated perfluoroalkyls. These alcohols can bereacted with acids to make esters with unique properties. The advantages maynot be readily apparent at first glance; however, the combination of a fatty acidand a perfluoro alcohol could impart water and oil repellency while giving themolecule some hydrocarbon compatibility to aid in formulation. Similarly, a dimethylpolysiloxane alcohol esterified with a fatty acid pro-vides a combination of silicone slip and feel with hydrocarbon compatibility.One may find unique applications for a silicone or perfluoroalkyl ester whichcould be more readily dispersed in a formulation. Silicone alkyl wax esters doexist commercially and provide interesting spreading and skin feel properties.These are easily formulated into the oil phase of an emulsion and help to makea cream that does not have a \"waxy drag\" when applied.B. Branched-Chain EstersAs we have already seen, branching in the hydrocarbon chain of fatty acidscauses the molecule to lose its ability to readily crystallize. This is becausebranching does not allow the close association of molecules, and thereforeprevents crystallization. So, branched-chain molecules remain fluid over a muchgreater temperature range. The result of using a branched-chain fatty alcoholto make an ester is similar in that more liquidity is imparted to the ester. Themelting point is reduced, the boiling point is reduced, and the esters are morefluid and have a higher spreading factor on skin. Also, the esters become lessoily-feeling and can be used to reduce the oily feel of other esters or oils. Now,let us look at the effects of some specific branched-chain alcohols.1. Short Branched-Chain AlcoholsThe shortest of the branched short-chain alcohols is isopropyl alcohol (IPA).We have already discussed the properties of many of the esters of isopropylalcohol (Table 6). One point to make is that IPA is a secondary alcohol asopposed to a primary alcohol. The esters of secondary alcohols are generallymore stable to hydrolysis than the esters of primary alcohols. Therefore, onewould expect to have formulations that are more stable with isopropyl myris-tate than if they were formulated with ethyl oleate. Indeed, IPM is used in

Emollient Esters and Oils 131Table 11 Comparison of Some Physical Properties of 2-Ethyl-hexyl (Branched-Chain) and Octyl (Straight-Chain) EstersChemical compound MP (°C) BP (°C)2-Ethylhexyl acetate -93 199Octyl acetate -38.5 2102-Ethylhexyl adipate -67.8 214Di(octyl) adipate 9.5-9.8 —many different formulations without significant hydorlysis and must there-fore be considered as providing adequate stability for cosmetic formulationpurposes. Now let us compare the properties of esters made from octyl alcohol versus2-ethyl hexyl alcohol. Both alcohols contain eight carbons, but 2-ethyl hexylalcohol is branched. From Table 11 it can be seen that the boiling points andmelting points of the branched-chain alcohols are lower than the straightchains. This shows that the effects caused by branching of the alcohol versusbranching of the acid are similar. So it doesn't really matter on which side ofthe ester the branching occurs. The point is that branching disrupts the abilityof the molecules to associate closely, and this reduces its viscosity, its boilingpoint, and its melting point.2. Branched-Chain Fatty AlcoholsPerhaps the best known of the branched chained fatty alcohols is isostearicalcohol. This is usually compared to stearic acid as an example of a branched-chain ester versus a linear ester. Esters made from linear fatty alcohols arehigher in melting and boiling points and generally feel oilier or waxier thancomparable esters made from a branched-chain alcohol. Why would one choose a branched-chain alcohol when there are alterna-tives available that can reduce the oiliness and greasiness of esters? One an-swer to this question is reduced irritation potential. Irritation occurring withhigher-molecular-weight fatty esters is generally much less than that seen withlower-molecular-weight fatty esters. Branching in an ester is one way to main-tain a high molecular weight and confer luquidity upon the resuhing ester.Hopefully, by this means one can make a fluid, low-viscosity, nonoily ester thatis also low in irritation. As you recall, liquidity can also be conferred by introducing a double bondinto either the fatty acid or the fatty alcohol portion of an ester. When this isdone, the resulting ester can suffer from reduced oxidative stability. This situ-ation does not occur with branching. Thus, to make an ester that has improved

132 Carson and Gallagher OH OH V\"2 NaOH ^\"2^ ^\"2 Heat * CH-CH2CH2PH2CH3 + H2O CH2 CH2 CH3 2 Ethyl Hexanol ^\"3Figure 8 Guerbet alcohol synthesis.oxidative stability and yet remains liquid is another reason to choose a branched-chain alcohol ester. In addition, branching can alter the skin feel of an ester. As an extremeexample, when a Guerbet alcohol is used for the alcohol portion of an ester,the result is a liquid ester that has a high molecular weight and low irritation.Guerbet alcohols are the condensation product of 2 moles of alcohol in whichthe reaction proceeds under basic conditions through the elimination of amolecule of water. The reaction scheme is shown in Figure 8. As can be seen,the reaction of two moles of n-butanol results in one mole of 2-ethyl hexanol.Often, though, the two legs of the branched Guerbet alcohol are made fairlylong such as by the condensation of n-octanol to make 2-hexyl decanol orn-decanol to make 2-octyl dodecanol; this dramatically affects the skin feel.The feel is described as \"cushiony.\" This is a somewhat difficult concept toestablish in words, but it describes the fact that the ester film is not readilyabsorbed by the skin and seems to act as a film or coating on the skin. Thiseffect is seen with longer fatty branched-chain alcohols and with multifunc-tional alcohols or acids that produce di-, tri-, or tetrafunctional esters. Thesewill be discussed in more depth below.IV. COMPLEX ESTERSThe easiest way to describe complex esters is to compare them to simple esters.A simple ester is one that has a single ester group. Complex esters are madeof either alcohols or acids, which have multifunctionality; therefore the result-ing esters have more than one ester group.A. Dibasic AcidsA great deal of work has been done by chemists in the esterification of dibasicacids. Much of this work was done prior to and during World War II to produce

Emollient Esters and Oils 133heavy-duty lubricating oils as replacements for the vegetable, animal, and pe-troleum oils that were then used as machine and motor lubricants (4). But,while much work has been done, not much of this work has been transferredto the cosmetics industry. At this point, we find ourselves with dioctyl sebecate,dioctyl adipate, and dioctyl maleate as the primary cosmetic esters of dibasicacids. The driving force for use of these esters is mostly economic. Adipic andsebacic acids are two of the least costly dibasic acids commercially available.In addition, 2-ethyl hexanol (octyl alcohol) is an inexpensive, readily availablecommercial alcohol. The dibasic acid esters can be made low in color (almostwater white) and low in odor. The esters that are produced are very fluid,light-feeling and extremely nongreasy. Higher-molecular-weight alcohols pro-duce more viscous and more oily products which may be more occlusive andlower in irritation. However, their use in cosmetic formulations is limited be-cause of their oiliness. Dibasic acid esters can enter into a formulation without one even beingaware of it. If a cream or lotion is packaged in plastic bottles made from poly-vinyl chloride (PVC) or polyethylene terephthallate (PETE), the plasticizerused in processing these polymers may be extracted from the plastic and intothe product. The most common plasticizer used is dioctyl phthallate. This isan inexpensive plasticizer that is made in large quantities and used to soften(plasticize) PVC and PETE resins to allow them to be processed. You areprobably familiar with dioctyl phthallate as the \"new shower curtain\" smell.As an odor, it is usually appreciated because it connotes \"newness,\" but dioctylphthallate in your formula is probably a contaminant. Its presence will usuallygo undetected unless it causes a problem. Normally, though, it is only noticedas a contaminant when gas chromatograms or high-pressure liquid chromato-grams of the product are run. So-called dimer acids are another type of dibasic acid. These are very high-molecular-weight acids usually made by dimerizing oleic or erucic acids. Theresulting diacids therefore contain either 36 or 44 carbon atoms (Fig. 9). Estersmade from these acids tend to be extremely oily and sticky due to their highmolecular weight. But they have extreme tenacity to skin and form very occlu-sive waterproof films on skin, OFigure 9 Dimer acid structure.

134 Carson and Gallagher Maleic acid is used to make a dioctyl ester, which has an extremely lowviscosity with a high spreading coefficient. This ester finds use in spread-ing bath oils and in reducing the greasy feel of other esters. In addition, thisester is a good solvent for oxybenzone and therefore finds use in sunscreenformulations. As the hydrogens on the center carbon are replaced by methyl groups, themolecular weight of the acid increases and therefore it will trend toward higherboiling points and melting points (4). Esters made from these acids show simi-lar tendencies.B. Polyhydric AlcoholsThe simplest of the glycols is ethylene glycol. This material has been used formaking esters and diesters for many years. The most common of these are thestearate esters. These are made by the reaction of stearic acid (usually triple-pressed stearic acid) and ethylene glycol in various ratios, to produce either aglycol monostearate ester or a glycol distearate ester. Variations on this themehave used diethylene glycol or triethylene glycol to add second or third etherlinkages between the ester groups in order to increase the polarity and improvewater dispersibility. These materials are used in surfactant products to pro-duce opacity and pearlescence. They are also used in stick products to producestructure and in emulsions as the low HLB emulsifier component. Ethoxylation of ethylene glycol or diethylene glycol is used to produce high-molecular-weight dihydroxy or polyether polymers of approximately 6000 dal-tons (or 150 oxyethylene repeat units). These materials are then esterified withstearic acid to produce viscosity-building agents. The well-known PEG-6000distearate (PEG-150 distearate) is a material of this type. More recently,materials based on pentaerythritol ethoxylates have been made available.These are the tetrastearate esters of PEG-150 pentaerythritol. These ma-terials have enhanced viscosity-building ability due to the three-dimensionalstructure conferred upon them by the central tetrahedral pentaerythritolmolecule. Similarly, esters can be made through the esterification of 1,2 or 1,3 pro-pane diols. These materials are commercially produced as monostearate ordistearate esters. Their uses are similar to those of ethylene glycol stearates inthat they are waxy, fatty, solid esters used to provide structure in stick formu-lations and as pearlizing and opacifying agents in shampoos and detergentproducts. Caprylic/capric esters of propylene glycol are also available that finduse in makeup formulations as emollients and as pigment-wetting agents. Esters of neopentyl glycol (2,2 dimethyl-1,3 propane diol) and trimethanolpropane are not in great evidence in the cosmetic industry, although theseesters are used commercially as aircraft and automotive engine lubricants.

Emollient Esters and oils 135Table 12 Comparison of Some Physical Properties of Pentaerythritol EstersChemical compound Specific Surface Spreading Kinematic gravity' tension' factor' viscosity'Pentaerythritol 0.950 24.7 4.7 56.0 tetracaprylate/tetracaprate 0.922 30.4 2.9 305.4Pentaerythritol tetraisostearate'All measurements taken at 25°C. The last member of the neopentylpolyol series is pentaerythritol. Esters ofthis material, as described before, are available as ethoxylates which are usedas viscosity-building agents in surfactant systems. Also, esters of capric/car-pylic acids and isostearic acids are available. The data for these two materialsare presented in Table 12. The capric/caprylic esters are low-viscosity esterswith a longlasting, lubricating skin feel. The capric/caprylic esters are used inmakeup products due to their fairly low spreading ability, nongreasy feel, andability to wet pigments. The tetraisostearate esters are much oilier because oftheir much higher molecular weight, but they are still liquid due to thebranched natures of the isostearic acid and the pentaerythritol. They find usein sunscreens because of their low spreading ability. Glycerin is one of the most common polyhydric alcohols and is the basicalcohol used by nature to make vegetable and animal oils. We have now re-turned to the triglycerides albeit from a synthetic direction in order to producematerials with new and potentially more useful physical properties. The firstexample of these new triglycerides is capric/caprylic triglyceride. These mate-rials are Cs and Cio straight-chain fatty acid triglycerides manufactured to pro-duce a material with consistent properties and low color and odor. Capric/caprylic triglycerides have a moderate spreading ability and a veiy light, slightlyoily feel. As discussed previously, if the glycerin is ethoxylated prior to esterification,the resulting materials can be water-soluble. For example, the ester of capric/caprylic acids with PEG-6 glycerine or the ester of coconut fatty acids andPEG-7 glycerine are water-soluble and can be used as foaming agents andwetting agents that provide an emollient skin feel.C. Multifunctional Adds and AlcoholsThe combination of multifunctional acids and alcohols has not been used toany great degree for cosmetic purposes. These reactions produce polymers

136 Carson and Gallagherthat are generally of high molecular weight and usually intractable. Modificationof these polymers through the use of branched-chain fatty alcohols and fattyacids (or alkoxylation of these materials) has not resulted in commerciallyacceptable materials to date. However, as described earlier, polyhydric alco-hols—multifunctional acids such as pimelic, tricarballic, and trimellitic—canbe used to make cosmetic esters.V. FUTURE CONSIDERATIONSAs already stated, much work has been done to synthesize esters and deter-mine their properties. As we continue to explore new avenues of chemistry,product applications, and cosmetic skin uses, no doubt we will develop newproducts to meet the needs that are discovered. One of the major directionsin which these products will go is toward safer, less irritating products. Thesewill probably come from increased use of higher-molecular-weight, branched-chain alkyl groups, alkoxylation, or silicones, or possibly the use of fluoro-carbons. In addition, future efforts will be directed to better characterize the physicalproperties of esters. While there is much information available, it is widelydispersed and not readily available in one source. Current efforts are directedtoward improving our understanding of the physical properties of esters andworking to develop a more complete database. As a further consideration, investigations are under way to develop meas-urements that will have greater use for the cosmetic industry. Specifically,these are an index to relate changes in viscosity to increases in temperature,and an index to compare skin spreading. The former could be envisioned assimilar to the viscosity index used in the petroleum industry, which relates todecreases in viscosity to increases in temperature. The latter gives a measureof the ability of an ester (or another compound) to spread when applied to theskin. Comparative data for various esters and standardized methodologies tomeasure these indices are planned for future publication,REFERENCES1. Balsam M, Sagarin E. Cosmetics Science and Technology. 2nd Ed. Krieger, 1992.2. The Merck Index. 11th Ed. Merck & Co., 1989.3. Remington's Practice of Pharmacy. 11th Ed.4. Synthetic Lubricants.5. Swern D. Bailey's Industrial Oil and Fat Products. 4th Ed. John Wiley & Sons, 1979.6. Truter EV. Woolwax Chemistry and Technology. Cleaver-Hume Press, 1956.

Emollient Esters and Oils 137SUGGESTED READING1. CRC Handbook of Chemistry and Physics, 72nd Ed., CRC Press, Boca Raton, FL, 1991-1992.2. Heilbron IM. Dictionary of Organic Compounds, Vol. 1-3, Oxford University Press, 1943.3. Leonard EC. The Dimer Acids, Humko Sheffield Chemical, 1975.4. Chemfinder, camsoft.com-Internet5. deNavarre MG. The Chemistry and Manufacture of Cosmetics, 2nd Ed., Continen- tal Press, 1975.6. Goldemberg RL and de la Rosa CP. Correlation of Skin Feel of Emollients to their Chemical Structure, J. Soc Cosmet Chem 1971; 22(10):634-654.

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7Proteins for ConditioningHair and SkinGary A. NeudahlCostec, Inc., Palatine, IllinoisI. INTRODUCTIONProteins make up the majority of the dry weight of living cells (1), fulfillingboth structural and functional roles. The building blocks of proteins are aminoacids, monomers which are so named because each has, in addition to a hy-drogen atom and an R group, an amino group (generally unsubstituted) anda carboxyl group attached to a central carbon atom. The identity of the R groupdefines the specific amino acid. At neutral pH this group may be anionic, cat-ionic, polar, or nonpolar (Table 1). Regardless, the monomer is amphoteric.Twenty genetically encoded amino acids are commonly found in proteins.Additional amino acids, as well as non-amino acid components, may also bepresent as a result of posttranscriptional modification. Proteins are polymers generated through the formation of peptide bondsbetween amino acids. These bonds are formed from amino and carboxylgroups with the consequential loss of a molecule of water and two chargedgroups per amino acid added. Thus, as polymerization proceeds, the growingmolecule (polypeptide) becomes decreasingly hydrophilic. The number ofamino acids constituting a protein subunit is typically 50 to 1000 (2). Withmultiple subunits, the overall molecular weight for a protein is typically be-tween 5,000 and 7,000,000 dahons (Da) (1). The genetically determined orderof attachment and the physicochemical environment yield the intra- and in-termolecular covalent, ionic, hydrogen, and nonpolar bonding which producea characteristic three-dimensional structure. When this structure matches that 139

140 NeudahlTable 1 Amino Acid R-Group ClassificationsCationic Polar Nonpolar Arginine Asparagine Alanine Desmosine\" Cysteine Glycine Histidine Glutamine Isoleucine Hydroxylysine* Hydroxyproline' Isodesmosine\" Serine Leucine Lysine Threonine Methionine Tyrosine PhenylalanineAnionic Proline'' Aspartic acid Tryptophan Glutamic acid Valine^Amino acids not genetically coded; synthesized via posttranscriptional modification,hrhe only genetically coded imino acid (R group and amino group fused to form a ring).found in nature (i.e., when a protein is in its native conformation), the pro-tein's inherent biochemical properties, including any enzymatic activity, maybe observed.A. Types of ProteinsFibrous proteins (protein chains arranged in parallel) include the water-swellable (but not soluble) structural proteins keratin, collagen, and elastin,major components of hair, skin, and connective tissue, respectively. Intermo-lecular crosslinks are common in these proteins, particularly those containingthe monomer cysteine (R = -CH2-SH). When oxidized, two cysteines formone cystine linkage (-CH2-S-S-CH2-). Such bonds are responsible for hair'sstrength as well as its ability to be reconfigured, or \"permanent waved.\" Globular proteins (protein chains compactly folded) include many whichare water soluble, such as serum albumin, hemoglobin, and catalase. As a gen-eral rule, these proteins are more susceptible to denaturation (permanent lossof native conformation and hence biochemical function) at high temperature,low concentration, extremes of pH, and air/solution interfaces (i.e., in foams)than are fibrous proteins (2). Some proteins, such as myosin and fibrinogen, contain elements of bothfibrous and globular proteins (long length coupled with water solubility).Others have various prosthetic groups, e.g., the various lipids in the lipopro-teins of blood plasma, the iron protoporphyrin of hemoglobin and catalase,the sugars and their derivatives of gamma-globulins, and the phosphated ser-ine residues of casein.

Proteins for Conditioning Hair and Skin 141B. Isolation of ProteinsPurification of proteins requires their separation from other organic materialsand from one another. Among the methodologies which may be utilized, de-pending on the purity required, are fractional crystallization from salt solution,precipitation at the isoelectric (isoionic) point (the pH at which the proteinhas no net charge), isoelectric focusing, gel filtration, electrophoresis, ultra-centrifugation, and various forms of chromatography (2). In many cases, partial hydrolysis is required to separate protein subunitsfrom one another or from matrix material and to promote water solubility.Hydrolysis enhances water solubility at near neutral pH, in part by increasingthe number of charged groups per unit chain length (each peptide bondcleaved yields an amino group and a carboxylate group). Limited hydrolysisoften reduces or eliminates enzymatic activity, and as the extent of hydrolysisincreases (yielding polypeptides and, ultimately, amino acids) all enzymaticactivity is lost. What remains is functionality related to specific amino acidspresent in the polypeptides, or, in the event of total hydrolysis, the function-ality of the individual amino acids.II. HISTORICAL DEVELOPMENTPerhaps the earliest purported application of unisolated protein in personalcare was the story of Cleopatra bathing in milk (3), with the milk proteins (inpart due to their phosphated serine residues) functioning as effective emulsionstabilizers, buffers, and conditioning agents. More recently, prior to the wide-spread use of high-purity soaps and synthetic surfactants, eggs were utilized asshampoos. Their use in hard water yielded improved hair luster while avoidingthe dullness which accompanied soap scum.A. Early ProductionProduction of a partial hydrolyzate of collagen (gelatin) was reported as earlyas the late seventeenth century in Holland, with the first commercial produc-tion occurring in the United States in 1808 (4). These accomplishmentspreceded an understanding of the chemical composition of the material: theamino acid glycine was purified from gelatin in 1820 by H. Braconnot (1), butgelatin's physical and chemical structure were not elucidated until the earlytwentieth century. Some typical gelatin production processes are shown inFigure 1. The vast majority of early protein hydrolyzates were derived from animals,and for good reason: significant portions of the animals slaughtered for foodwere unsuitable for this or other purposes unless modified and so would

142 NeudahlFigure 1 Some typical gelatin production processes. (From Ref. 4.)otherwise be discarded. So methods were developed to produce proteinhydrolyzates of skin, connective tissue, and bone (e.g., gelatin and hydrolyzedelastin), concurrently providing an environmental benefit. Plant-derived pro-tein hydrolyzates arose primarily to meet a new definition of environmentalfriendliness (5).

Proteins for Conditioning Hair and Skin 143B. Use of Hydrolyzates in Personal Care ProductsThe first protein hydrolyzates developed for personal care applications werereported to have been prepared in the early 1900s by the German companyChemische Fabrik Gruenau Berlin (3). They arose from observation of thealkaline dyeing of wool (which, like human hair, consists primarily of keratin).Dye baths laden with protein hydrolyzate proved markedly less damaging tothe wool. Subsequent testing confirmed similar dramatic benefits for collagenhydrolyzates at a 10% use level in reducing human hair damage during bleach-ing and permanent waving (6) and identified the preferred method of hydro-lysis (enzymatic) and optimal molecular weight [1000 to 2000 Da (7,8)] andpH [near neutral for bleaching hair, slightly alkaline for virgin or permanentwaved hair (9)] for maximum substantivity. Quantification of hydroxyproline(an amino acid found almost exclusively in collagen) content of collagen-treated materials proved an effective means of establishing substantivity (10).An early patent in this area references the use of gelatin on previously tintedhair to resist dye action during the coloring of new growth (11).1. Protein Effect on HairTesting also affirmed that substantial quantities of at least some hydrolyzatespenetrated through the cuticle (hair's outermost, shinglelike protective layer)into the cortex (the fibrillar, main structural component) and that the amountof hydrolyzate bound increased markedly with increasing damage (virgin <bleached <*: bleached and waved) (12). These hydrolyzates were shown toreduce cuticle damage and fiber embrittlement when present during thebleaching and waving processes (6).2. Protein Effect on Sl<inEvaluation of hydrolyzates applied to human skin revealed that penetrationwas limited to the outer layers of the stratum corneum (4,8). Hydrolyzates thusfunction as moisturizers and, as a result of their film-forming properties, irri-tation mitigants in the presence of strongly anionic surfactants (13).C. Improvements in IVIanufacturingThe collagen hydrolyzates used in the aforementioned studies were dark incolor, high in ash (inorganic salts), and malodorous. The efforts of many pro-ducers gradually yielded lighter colors, lower ash, and less objectionable odor,allowing their application in a broader range of products. Further, with in-creasing interest in products from renewable (i.e., plant) sources, proteinhydrolyzates from other sources—animal, plant, and microbial—have beencommercialized and International Nomenclature Cosmetic Ingredient (INCI)names (14) assigned, yielding a wide range of materials and potential function-alities from which to choose.

144 Neudahl Building on the development of hydrolyzates, a variety of condensationproducts were then generated and evaluated for application in personal care(4,8). Reaction of fatty acid chloride (RCOCl, R = Cs-Cis) with primaryamino groups of the hydrolyzate in alkaline media attached the R groupvia an amide linkage to the hydrolyzate. These hydrolyzates thus became an-ionic surfactants. Depending on the length of the polypeptide chain and theidentity of the R group, mild wetting, foaming, conditioning, plasticizing, andemulsifying properties were achieved. Neutralized C12 and CM versions (e.g.,TEA-lauroyl hydrolyzed collagen) behaved similarly to synthetic detergentbut with much less eye and skin irritation. Their Cie and Cis counterparts (e.g.,potassium stearoyl hydrolyzed collagen) behaved similarly to soaps. Reaction of fatty tertiary amines with primary amino groups attached thesemoieties to the hydrolyzate. A quaternary nitrogen atom resulted, impartingcationic character to the hydrolyzate, which was maintained at high pH (> 11).These condensates were thus more substantive to hair and skin than the un-modified hydrolyzates and imparted conditioning benefits to hair and skin.Indeed, quaternium-76 hydrolyzed collagen, the coconut-based quaternaryhydrolyzate, was as effective as stearalkonium chloride at a 2% actives level inimproving the wet combability of hair and was markedly less irritating to skinand eyes (15). Additional modifications have been made since by a variety of manufac-turers, and representative products will be described in the sections whichfollow.III. GENERAL FORMULATING CONSIDERATIONSCertain formulation guidelines apply regardless of intended area of applica-tion. Among the considerations are microbiological preservation (proteins,their hydrolyzates, and most derivatives are excellent nutrients), odor andcolor stability (free amino and sulfhydryl groups are reactive toward a numberof commonly employed cosmetic ingredients and substrates), conformationalstability (enzymes retain their activities only when in, or very close to, theirnative states), molecular weight (humectancy, film forming, and the potentialfor allergenicity vaiy with polymer size), amino acid composition (humectancyis greater with more charged amino acids), ash (salt) content, and net charge(substantivity is highly dependent on pH).A. Preservation of Protein-Based MaterialsProteins are components of every living thing, attesting to the broad-basedcompatibility of their monomers, the amino acids. It should thus not be sur-prising that proteins and their hydrolyzates and derivatives are readily biode-

Proteins for Conditioning Hair and Skin 145gradable. A suitable preservation system must thus be incorporated in prod-ucts containing both water and protein-based material. The protein productssold as aqueous solutions utilize a variety of preservation systems. Most fre-quently employed are the parabens (methyl- and propylparaben, in particu-lar). Finished products containing proteins in their native states (generallypresent to make use of their enzymatic activities) require preservatives whichhave very low reactivity toward the protein and so do not appreciably modifythe conformation of the protein. A combination of parabens and phenoxy-ethanol at a level of up to 1 % by weight of the formulation may be employed.When hydrolyzates and their derivatives are utilized, more reactive (andmore cost-effective) preservatives can be utilized. Such agents may includequatemium-15, imidazolidinyl urea, diazolidinyl urea, DMDM hydantoin, andmethyl[chloro]isothiazolinone, with or without parabens. Specific preserva-tion systems are referenced by some manufacturers (16,17). Certain preserv-atives are incompatible with proteinaceous matter, particularly at high con-centration. A striking example is the firm gel produced after overnight storageat room temperature of a solution of approximately equal proportions of 37%formaldehyde and 55% hydrolyzed collagen (2000 Da).B. Protein Formulation Stability ConcernsOdor and color stability can be significant concerns when formulating withprotein-based materials. As a start, proteins and hydrolyzates must be storedunder cool, dry conditions, taking precautions to prevent contamination. How-ever, even with proper storage, the free amino groups are potential reactionsites for carbonyl and aldehyde groups. As a result, formulation with fragranceoils containing these groups may result in reaction with the free amino groupsto produce changes in odor and/or color of the product. Color changes are alsoan area of concern when formulating with sugars, as their aldehyde groups mayreact with free amino groups via the Maillard reaction to induce brown colorformation.1. Using Proteins Containing Sulfhydryl GroupsUse of protein-based material containing sulfhydryl groups presents its ownunique challenges. The hydrolyzed proteins in particular have a sulfurous odorwhich requires some measure of masking. Further, these sulfhydryl groups(present as the amino acid cysteine, in polypeptides containing this amino acidor in derivatives thereof) are frequently employed due to their capability toundergo sulfhydtyl exchange, particularly with the keratin of hair. Oxidationof these groups to cystine linkages or cysteic acid, which may occur upon ex-posure to air or oxidizing agents in the product, reduces the effectiveness ofinterchange and changes the odor of the product. Further, precipitation of

146 Neudahloxidized (\"dimerized\") material often results. Auxiliary reducing agents aretherefore often employed to maintain the sulfhydryl group's reduced state.When hydrolyzate odor must be minimized, use of the spray-dried version ofa product may prove helpful, as a portion of the odor-producing molecules arevolatilized and removed during the drying process.2. Maintaining Confom^ation Stability of ProteinsConformational stability is of concern for both structural proteins and en-zymes, the former so that consistent binding and tactile properties are en-sured, the latter so that enzymatic activity is maintained. As noted previously,permanent loss of native conformation is prevented by avoiding high tempera-ture, low concentration, extremes of pH, and foaming. Unfortunately, theacceptable ranges differ widely from protein to protein and must be deter-mined empirically (e.g., for soluble collagen, temperatures above 30°C shouldbe avoided).C. Effects of Molecular Weight on Protein PropertiesMolecular weight primarily determines a number of properties of hydro-lyzates. The molecular weights cited for hydrolyzates represent average (ormedian) values for relatively broad (and frequently nongaussian) distribu-tions. Thus, a range of 1000 to 5000 Da for a hydrolyzate may be considered\"narrow.\" Humectancy (hygroscopicity) is greatest for individual amino acids,which can absorb several times their weight in water at high (>80%) relativehumidity. Humectancy diminishes exponentially as the size of the polypeptideincreases. Nonocclusive, protective colloidal film-forming properties increaseconcurrently. At low molecular weight, hydrolyzates may be considered non-toxic (18) and hypoallergenic. The potential for toxicity or allergic responseincreases with molecular weight, however, with the threshold dependent onprotein type, conformation, prosthetic groups present (19), and site of contact.Allergic reaction is most likely to occur when material is inhaled as a dust oraerosol (20).D. Effects of Protein Amino Acid DistributionAmino acid composition is important not only because of its effect on con-formation, but also because of its effect on humectancy and solubility. Bothhumectancy and water solubility of proteins and hydrolyzates increase as theproportion of amino acids with charged R groups increases. Thus, dependingon the particular attributes desired in the finished product, one protein sourcemay be preferred over others, based on its amino acid content. The amino acid

Proteins for Conditioning IHair and SIdn 147profiles for a number of proteins are presented in Table 2 (as numerical per-centages, i.e., mol%), Table 3 (animal and yeast proteins as weight percent-ages, i.e., %wt), and Table 4 (plant proteins, as wt%, i.e., g/100 g). Asparagineand glutamine typically assay as aspartic acid and glutamic acid, respectively,as the amide bonds in their R groups are hydrolyzed when utilizing the classicalassay procedure. Source-dependent variations in apparent composition areevident in each table.E. Effects of Other Protein ComponentsInorganic salts (typically measured as ash) may remain in a protein-basedproduct through its isolation, be added in the form of a buffer, or result fromthe alkaline or acid hydrolysis of a protein or its subsequent derivatization. Formany formulations, inorganic salts present no concern as long as their level isconsistent from lot to lot. On occasion, however, they may adversely effectemulsion stability in creams and lotions or yield cleansing systems with viscos-ity already over the salt curve (i.e., salt content higher than required to achievemaximum viscosity in the system). In such cases, differently processed materialmay resolve the problem.F. Importance of Protein Net CiiargeThe net charge of protein-based products in finished formulations is importantfor several reasons. First, substantivity is higher when hydrolyzates have a netpositive charge (i.e., are below their isoionic points), as both skin and hair havenumerous anionic sites available for binding under typical conditions. Second,the solubilities (and frequently stabilities) of native proteins are typically low-est at their isoionic points. Thus, manufacturing procedures for finished prod-ucts are best designed to preclude fluctuation of batch pH back and forthacross the isoionic point of a purified protein. Third, many proteins consist ofseveral subunits which assemble properly only within a certain pH range. Fur-ther, even many single-subunit proteins require a certain pH range to take onthe correct conformation to exhibit enzymatic activity.iV. HAIR CONDITiONINGConsumers know, whether through folklore or experience, that proteins(actually, protein hydrolyzates) and amino acids work to condition and mois-turize hair effectively (21). Nonetheless, concerns over what constitutes \"pro-tein\" in products resulted in a legal definition in the United States (22). Se-lected underivatized hydrolyzates with demonstrated performance attributesfollow.

Table 2 Amino Add Profiles (mol%) for Selected Protein SourcesAmino Collagen Wool Human Silk Silkadd keratin hair [S] [B] fibroin fibroinAlanine 11.6 6.3 4.7 30.6 29.82ArginineAspartic add* 3.6 6.9 6.3 0.1 —Qfstineyi 4.6 6.7 5.4 ZI 1.17 — 7.8\" 16.0\" Trace —Glutamic add^ 7.6 14.9 12.9 IS 0.41Glydne 33.8 7.0 6.1 42.9 45.99HistidineHydrra^lysine 0.4 1.0 1.0 Trace —HydroT^roline 0.2 — — — —Isoleudne 10.6 — — — — 1.3 3.5 3.3 1.0 033Leudne 2.7 8.1 6.2 0.6 0.17Lysine 2.5 Z8 2.8 0 5 —

a> Pearl Milk Wheat Wheat Soya Soya Oatconchiolin casein protein gluten [B] protein bean [S] 14.0 4.5 4.2 3.4 bean 1.4 Z8 0.1 2.3 3.7 9.2 7.3 3.0 3.1 7.3 7.2 8.46 0.4 Z2 0.9 11.4 1.6 4.78 — 1.3 15.3 15.42 20.6 39.6 36.9 0 3 1.03 3.0 20.8 3.2 6.8 5.8 23.6 24.34 4Z9 2.8 Z2 1.6 3.9 0.2 2.7 9.5 11.65 Z — — — 3.5 1.39 — — — — — (D — — —— C 4.4 1.6 3.3 —— 3.2 4.0 0a) 7.2 6.5 6.8 3.8 ZIO 6.3 7.3 1.1 1.3 6.3 7 1.2 Z7 7.9 6.19 4.4 3.16

Methionine 0.3 0.9 0.6 TracePhenylalanineProline 13 2.3 1.8 2.3 5.69 115 8.7 7.0 03Serine 3.1 7.9 10.5 9.7 11.45ITireonine 1.8 5.5 7.2 0.9 1.12Tyrosine 0.1 2.7 2.3 4.9 1.66Valine 3.0 6.8 5.8 2.6 2.19^See comments in text regarding asparagine and glutamine content. Cysteic add, an oxidative reaction product of cyst[e]ine, was present at 0.2 mol% iSources:Collagen, silk [S] fibroin, pearl conchiolin, milk casein, wheat protein and soya [S] bWool keratin and human hair from Promois WK-Q technical data sheet EKPHOOSilk fibroin [B] from Solu-Silk Protein Data 1301/Revl, Brooks Industries.Wheat gluten from WPH-DGF1191 Product Information, DGF Stoess, Feb. 1992.Soya [B] bean from Soln-Soy EN-25 Technical Data 1400/1, Feb. 1990, Brooks IndOat from Hydrolyzed Oat Protein HOPA Product Information, Canamino, Inc.

0.4 2.4 1.4 LI 13 1.0 0.98 31.2 3.0 4.5 4.6 3.9 3.5 1.09 s.2.7 123 14.4 14.0 5.6 7.2 5.20 37.5 7.7 6.1 5.6 4.7 3.2 6.75 M2 3 5.1 2.1 2.6 3.7 1.2 3.26 3\"Trace 33 1.5 Z4 1.2 1.6 1.05 o 4.2 5.2 3.134.5 5.7 2.7 4.3 o in wool keratin and 0.1 mol% in human hair. 3 Q. bean from Promois Digest, Seiwa Kasei Co., Ltd., May 1995.O, Seiwa Kasei Co., Ltd., Apr. 26,1996. 3 . 3dustries. a CO

Table 3 Amino Add Profiles (g/100 g) for Selected Animal and Yeast PAmino add Pork Calf Bone Fish skin skin gelatin Collagen collagen gelatin gelatin (typeB) [H] (type A) (lypeB)Alanine 8.6-10.7 9.3-11.0 10.1-14.2 93 8.6Arginine 8.3-^.1 8.55-8.8 5.0-9.0 83 16.7Aspartic add^ 6.2-6.7 6.6-6.9 4.6-^.7 63 3.9cystine/2 TraceGlutamic add' 0.05 Trace 8.5-11.6 — — 113-11.7 11.1-11.4 9.6 4.2Glydne 26.4-30.5 26.9-27.5 24.5-28.8 24.6 25.6Histidine 0.85-1.0 0.74-0.78 0.4-0.7 0.9 1.7Hydroxylysine 0.91-1.2 0.7-0.9Hydrojqfproline 1.04 14.0-14.5 11.9-13.4 — —Isoleudne 13.5 1.3-1.54 1.36 1.7-1.8 13.9 0.8 1.6 1.2Leudne 3.1-3.34 3.1-3.4 2.8-3.45 33 2.2Lysine 4.1-5.2 4.5-^.6 2.1-436 3.8Methionine 0.8-0.92 0.8-O.9 0.0-0.6 1.0 —Phenylalanine 2.1-2.56 2.2-2.5 1.3-2.49 2.3Proline 16.2-18.0 14.8-16.35 13.5-15.5 13.6 1.0 — 8.0

Ul oProtein Sources Cattle Collagen Bovine Human Hair Bovine hide [C] collagen hair keratin elastin Yeastcollagen9.4 8.0-11.0 9.6 4.5 5.5 18.2 7.167.4 7.8-9.0 73 9.1 11.0 1.5 9315.5 5J-9.0 5.6 9.0 9.4 2.0 9.21— 0.0-0.9 — 13 13 — —9 5 10.0-11.7 10.6 18.1 20.0 3.9 9.3823.0 20.0-30.5 23.1 5.6 7.0 23.1 14.020.7 0.7-1.0 1.0 13 1.5 2.8 1.300.8 0.7-1.2 23 — — ——12.0 12.1-14.5 11.2 — — 2.7 —1.4 1.3-1.8 1.4 2.4 0.9 3.2 1.702J8 2.8-3J 3.1 4.6 1.4 7.5 2.053.9 3.9-5.2 3.8 3.6 4 3 1.4 4.070.7 0.7-0.9 1.8 0.8 0.2 — 1.17 Z1.9 1.1-2.6 1.9 2.3 1.6 5.1 3.87 Can.13.8 13.7-18.0 123 93 9.5 11.9 — 3r

Serine 2.9-4.13 3.2-4.2 3.4-3.8 3.0 4.7Threonine 2.2 2.2 2.0-2.4 2.0Tryptophan 2.1Tyrosine — — — —Valine — 0.44-0.91 0.2-1.0 0.0-0.23 03 — 25-2.8 2.6-3.4 2.4-3.0 3.2 1.7^ e e comments in text regarding asparagine and glutamine content.Sources:Gelatins from Gelatin, New York: Gelatin ManufacturersCollagen [H] from Amino Add Distribution of PepFish collagen from Solu-Mar EN-30 Technical Data 1090/1, Brooks Industries, FeCattle hide collagen from Hydrocoll Technical Data, Issue 2, Brooks Industries, NCollagen [C] from Crodata: Crotein SPA, SPO and SPC, Croda, Ina, June 14,198Bovine collagen, hair keratin, and bovine elastin fromHuman hair from Crodata: Crotein HKP—^Keratin Amino Acids, Croda, Inc., JanYeast from VEGP/2: Plant Proteins, Brooks Industries, Spring 1992.

— 2.9-4.1 2.6 13.1 134 1.2 5.68 •o— 1.8-2.6—— 1.7 9.1 8.1 1.2 4.08 (D0.2 0.2-1.0 — — — — 3.25 5'2.2 2.1-3.4 — 0.8 0.5 — 1.28 (0 ZO 5.2 4.3 144 4.24 3- o a3.s Institute of America, 1993 (Table 1, p. 8). Sptein, Hormel Foods Specialty Products. Unpublished. 5\"eb. 1990. ***Nov. 1990. Diamalt, Inc. o> 85. ^ 3 Products for Apphcations in Cosmetics, -_n. 23,1982. E ai

Table 4 Amino Add Profiles (g/100 g) for Selected Plant Protein SAmino Soy Soya Soy Soy Com Potatoadd [H] [B] [C] zein bean PI 5.43Alanine 5.5 4.5 12.84 4.40Arginine 8.0 3.50 4.1 7.2 4.15 14.69Aspartic add\" 11.6 8.42 7.9 12.3 6.77 0.73Cystine 2.0 13.56 12.4 1.0 2.35 13.86Glutamic add\" 19.6 1.23 20.1 18.68 26.82 21.9 8.92Glydne 43 4.0 4.5 5.35 1.70Histidine 23 2.10 2.9 2.6 2.50 5.08Isoleudne 4.9 321 4.9 3.8 3.78 10.22Leucine 6.7 4.18 7.9 7.4 11.81 6.04Lysine 6.4 6.59 6.5 6.4 3.20 2.90 1.81Methionine 23 1.0 13 1.71 4.74Phenylalanine 43 1.23 5.2 4.8 0.62 5.82Proline 53 5.87 4.9 5 3 11.19 4.67Serine 4.4 4.61 4.7 5.4 5.61 4.98 4.94Threonine 4.0 3.6 4.1 450 0.20Tryptophan 0.9 3.92 1.2 0.20Tyrosine 3.0 1.44 23 3.6 0.20 6.52Valine 4.4 1.44 5.1 4.7 539 3.97\"See comments in text regarding asparagine and glutamine content.Sources:Soy [H] from Peptein VgS, Document 09-020-5790 Revision C, Honnel FoodSoya [B] bean, wheat [B] gliadin, com zein, potato, and golden pea from VEGSoy [D], wheat gluten [D], and rice gluten from Products for Applications in CSoy [C\ from Crodata: Hydrosoy 2000/SF, Croda, Inc., July 14,1984.Wheat [C] from Oodata DS-23: Hydrotriticum 2000, Croda, Inc., Aug. 17,19Wheat [H] gluten from Peptein VgW, Document 09-019-5790 Revision B, HoOat protein (whole oat) from Ceapro, Inc., unpublished.

Sources Wheat Wheat Wheat Wheat Rice Oat Ol [C\ [H] gluten protein lO Crolden [B] [D] pea 2.7 gliadin gluten gluten 5.9 6.4 3.2 85 6.1 4.47 3.1 1.60 2.1 5.2 9.2 8.6 8.80 1.8 2.01 3.4 3.5 2.4 11.86 36.8 2.24 33 2.9 20.4 243 0.90 1.24 1.7 4.6 19.93 3.5 22.91 40.9 383 3.4 8.8 2.2 3.1 5.0 2.2 4.33 3.4 4237 23 3.8 9.1 2.6 2.66 73 1.07 4.1 2.2 3.7 75 4.58 1.7 1.87 6.8 4.8 4.1 8.46 4.04 1.5 7.2 2.1 758 1.5 1.12 1.7 5.9 1.8 5.4 13 4.4 43 0.98 12.0 0.79 5.2 2.1 4.9 3.9 5.14 5.7 3.11 13.0 4.8 3.7 5.1 4.93 8.28 4.1 10.8 3.68 2.9 3.20 2.4 3.8 2.0 3.4 6.9 15 2.94 Z9 1.60 13 2.4 Z9 0.51 4.1 0.06 4.2 0.7 3.9 331 035 33 4.92 X12 4.2ds Spedalty Products, Dec. 1995. IGP/2: Plant Proteins, Brooks Industries, Spring 1992. Cosmetics, Diamalt, Inc.994.onnel Foods Specialty Products, Dec. 1995.

Proteins for Conditioning Hair and Skin 153A. Hydrolyzed CollagenHydrolyzed collagen, the first broadly utilized functional proteinaceous mate-rial for hair care, remains in widespread use today. Collagen is the most com-mon protein in the human body, comprising 30% of total protein content.More than a dozen variants are found in various tissues, including tendon,cartilage, bone, and skin (23). Types 1 and 3, produced primarily by young skin,have the highest water-binding capacity. With advancing age, crosshnking ofcollagen increases and water-binding capacity decreases, contributing to anincrease in the number of fine lines and wrinkles. Collagen presents an excellent case study regarding the importance ofprocessing in relation to an end product's properties and performance.The gelatin from which hydrolyzed collagen is formed is classified as eithertype A or type B, depending on whether its precursor is acid (A) or alkali(base, B) treated. The significance of this treatment hes in the isoionic pointof the gelatin, and subsequent hydrolyzates, which result: pH 7-9 for type Aand pH 4.7-5.4 for type B (4). Thus, type A gelatin and its hydrolyzates aretypically much more substantive to both skin and hair (anionic substrates)at the neutral to slightly acidic pH of most cosmetic products, as they carrya net positive charge in this range. Type B products must be quaternizedto achieve such substantivity because of their greater net negative charge,which maybe attributed to conversion of glutamine and asparagine to glutamicacid and aspartic acid, respectively, during processing. This replaces polar Rgroups with anionic ones (unless adjusted to very low pH). The gelatin is then further hydrolyzed using acid, base, or enzymes to formcollagen hydrolyzates. Chemical hydrolysis necessarily adds to ash (salt) con-tent, which can destabilize emulsions. Enzymatic hydrolysis does not contrib-ute to ash content and has the further benefits of generally producing a lightercolor and a product with more consistent molecular weight (24). Benefits ofcollagen hydrolyzates are typically and most readily observed in finished prod-ucts when protein hydrolyzate solids are present at 2% or more in leave-inproducts and at 5% or more in rinse-out products. Hydrolyzates are stable inthe range of pH 3-12 (16). Hydrolyzed coUagens of 5000 to 15,000 Da are excellent moisturizing filmformers. Their relatively high molecular weight minimizes absorption, depos-iting most of the collagen on the hair's cuticle. Added body, resiliency, shine,and manageability, as well as reduced static charging, is the result, particularlyfrom leave-in products. Hydrolyzed collagen of 2000 Da has demonstrated substantivity to hair,increasing with the extent of damage to the hair (bleached and permanentwaved > bleached > neither). Further, the more damaged the hair, the greaterthe difference in substantivity between type A- and type B-derived material is

154 Neudahlobserved. The substantivity is the result of both adsorption (coating) and ab-sorption (penetration) of the hydrolyzate. Surface adsorption contributes toshine, combability, and volume (24), while penetration of the cortex yieldsincreased tensile strength and elasticity. Temporary mending of split endswhen applied as a leave-in product (25) at 2.5% solids level (above thislevel, damaged hair picks up little additional hydrolyzate) (24) and mois-turization of the hair also result, improving both the hair's manageabilityand appearance. Type A gelatin-derived hydrolyzed collagen has appreciablesubstantivity to hair from pH 4 to 10, with the greatest substantivity from pH6 to 9. Hydrolyzed collagen is available as a powder and in preserved aqueoussolution form. The powder can be added with mixing to water for readydissolution. Hydrolyzed collagen (and other hydrolyzates and small ioniccompounds) are best added to an emulsion-based product after the emul-sion has been formed, as salts and similar ionic materials may adverselyaffect emulsion formation. In surfactant systems such as shampoos, hydro-lyzed collagen acts as a foam stabilizer and booster when used at one-fourththe level of active foamer on a solids basis. The hydrolyzate's colloidal,film-forming nature strengthens the bubble film, prolonging the time untilbreakage (16).B. ElastinElastin is the second most common connective tissue protein after collagen,constituting 60-80% of the dry weight of blood vessels and ligaments. Itsunique amino acids are desmosine and isodesmosine. In skin, elastin fibersenmeshed in collagen provide skin with its elastic strength (23). Excessive sunexposure leads to abnormal, disoriented elastin fibers and folding of the epi-dermis (i.e., wrinkles) (26). Like hydrolyzed collagen, hydrolyzed elastin of2000 to 5000 Da is a good film former, but is much less hygroscopic due to itsmuch lower polar and charged amino acid content (see Tables 2 and 3). As aresult it has much higher hydroalcoholic and polyol solubility and can reduceswelling of hair during permanent waving and coloring processes. Like otherlow-polarity protein hydrolyzates, such as silk (17), it may be preferable tocollagen (and other more hydrophilic hydrolyzates) where humidity resistanceis desirable.C. KeratinKeratin, as the primary structural protein of hair (and nails as well), provideshair its strength. Keratin hydrolyzates are notable primarily because of their

Proteins for Conditioning iHair and Skin 155high cystine content (see Tables 2 and 3), which, in a reducing environment,allows for sulfhydryl interchange with cysteine residues in hair. High-molecu-lar-weight hydrolyzed keratin (125,000 Da) demonstrated long-term substan-tivity and conditioning effects when applied to reduced hair (i.e., in the midstof permanent waving) at a 1.5-5% solids level (27). Patents related to alkalinepermanent waving and the better afterfeel which resulted from incorporationof these hydrolyzates were issued in the early 1980s (28,29).D. Vegetable Proteins1. Soy and Wheat ProteinsSoy and wheat protein hydrolyzates produce benefits similar to those notedfor collagen, but also have the added potential for hair protection and condi-tioning through bonding via disulfide interchange. Collagen does not have thiscapacity, because of its very low cystine content (the presence of cystine incollagen is an indication of impurity). Hydrolyzed wheat protein in a perox-ide-based hair bleach at 2% solids reduced formation of cysteic acid (an un-desired oxidative by-product) by a third (30).2. Hydrolyzed Sweet Almond ProteinHydrolyzed sweet almond protein, contrary to its INCI name, actually containsboth polypeptides and oligosaccharides as major components. A significantcarbohydrate content is typical of plant- (but not animal-)derived proteins.The result is conditioning by both penetration (of the polypeptides) and coat-ing (by the ohgosaccharides). In a leave-in product, enhancement of moistureretention and shine would thus be expected (31). Observable strengthening ofdamaged hair and protection of hair fibers would be expected at a use levelsimilar to that required for hydrolyzed collagen.3. Hydrolyzed Wtieat ProteinsHydrolyzed wheat protein (and) hydrolyzed wheat starch, similar to hydro-lyzed sweet almond protein, conditions by both penetrating and coating. Typi-cal of collagen and soy hydrolyzates, substantivity to normal hair increases withconcentration, rapidly to 2% actives and plateauing above 5% actives. Studiesof stress relaxation and elasticity on hair damaged with a 2% sodium hydroxidecream for 15 min suggested a reduction in brittleness at low relative humidity(RH) and a reduction in limpness at high RH for hair pretreated with 5%hydrolyzate solids (32). Other, more readily apparent benefits to be expectedfrom protein/oligosaccharide combinations in leave-in products are improvedbody and shine (33).

156 Neudahl4. Hydrolyzed Oat ProteinHydrolyzed oat protein can also provide substantivity, shine, split-end repair,and a protective barrier to hair. Aspartic and glutamic acids, the two aminoacids with carboxyl-containing R groups, together account for 40% of theamino acid content of the protein (34), making for improved humectancy.Exceptionally light color allows greater formulation latitude. A10% use levelis recommended for irritancy mitigation in shampoos, and a 2% level in for-mulated leave-in and rinse-out conditioners.E. Amino AcidsWheat amino acids are derived from wheat protein, fully hydrolyzed to itsconstituent amino acids. Like oat protein, 40% of the amino acids have car-boxyl-containing R groups (see Tables 2 and 4). The small size of amino acidsallows absorption and retention in the hair fibers (35). Their hygroscopic na-ture allows them to function as humectants when applied directly to hair at alow 0.2% active solution (36). In rinse-out conditioners, a use level of 0.5%actives is recommended to enhance hair's equilibrium moisture content. Collagen \"amino acids\" covers hydrolyzates which vary by manufacturerfrom actual amino acids to short polypeptides (<700 Da), Regardless, theyare highly hygroscopic and so excellent humectants with very efficient mois-ture-binding properties for hair. Substantivity is somewhat greater than for thehigher-molecular-weight hydrolyzates (24). Penetration results in more pli-able hair with a soft, nontacky feel, particularly at high relative humidity. Certain amino acids find application in specific areas. The predominantlyanionic amino acids glutamic acid and aspartic acid are particularly effectivehumectants. Taurine has been patented for use as a \"protein magnet,\" to en-hance deposition of positively charged ingredients in damaged hair (37). Cys-teine and derivatives have found application in permanent waving composi-tions, contributing to the reduction of disulfide bonds necessary as the firststep in reconfiguration of the hair.F. Quaternized Protein HydrolyzatesQuaternization of protein hydrolyzates typically raises their isoionic points topH 10 or higher, regardless of their original isoionic points. It thus tendsto equalize (and improve upon) the performance of collagen hydrolyzates,whether made from type A or type B gelatin. Like the underivatized hydro-lyzates, substantivity increases with the extent of damage to the hair. A slightincrease in moisture binding has also been observed (for wheat and soyquaternaries). The increased cationic character yields enhanced substantivity,even under the alkaline conditions encountered in permanent waving, oxida-

Proteins for Conditioning Hair and SItin 157tive coloring, and straightening of hair. Hydroxypropyltrimonium- and propyl-trimonium-substituted protein hydrolyzates thus extend the benefits of theunderivatized hydrolyzates to alkaline pH, allowing effective protection andconditioning during \"chemical processing\" (covalent modification) of hair.Further, such products in typical cleansing systems yield denser and more sta-ble foam. Certain products can markedly reduce the irritation potential ofthese systems as well. Five parts sodium lauryl sulfate to one part of one manu-facturer's propyltrimonium hydrolyzed collagen reduced irritation ratingsfrom severe to nonirritating, and its addition to a wide array of commercialsurfactant-based products yielded irritation reduction (38). Incorporating a long alkyl chain in the quaternary imparts the conditioningcharacteristics expected of traditional quaternaries such as stearalkoniumchloride, but with much lesser irritation and much greater compatibility withanionic surfactants. As such, they may be utilized in clear conditioning sham-poos, conditioners, and styling mousses, enhancing wet and dry combability,luster, feel, and static control. Quatemium-79 hydrolyzed proteins added to10% sodium lauryl sulfate improved combability to at least 0.4% (solids) andfeel to 0.1%, while substantivity increased to 2% with only a small decrease infoam generation (39). Typical use levels for fatty alkyl quaternary protein hy-drolyzates are 0.4-4% (solids basis). Fatty quaternary hydrolyzates of proteins containing cyst[e]ine residues,such as wheat, may be particularly appropriate for permanent waving solutions,as they offer the potential for \"permanent conditioning,\" i.e., grafting fattymoieties covalently to the hair via disulfide interchange. While substantivity isessentially independent of fatty moiety chain length (Cio-Cis), it decreases bya factor of 4 between pH 4.5 and 8.5 (40).G. Other Chemically Reacted ProteinsReaction of fatty acid chloride with primary amino groups of hydrolyzatesyields anionic surfactants. Unneutralized, they may be incorporated in po-mades, functioning as dispersants, to assist in pomade removal during sham-pooing. When amine neutralized (e.g., AMP-isostearoyl hydrolyzed collagen)they have excellent alcohol solubility and may be incorporated in hairsprayformulations as resin plasticizers. Potassium cocoyl hydrolyzed collagen is alow-irritation, relatively high-foaming surfactant which can be utilized, gener-ally with other surfactants, to produce very mild (e.g., baby) shampoos. It isalso an effective dye leveler in hair coloring applications. Triethanolamine-neutralized material combined with sorbitol yields greater compatibility in tra-ditional shampoo systems, allowing formulations to pH as low as 5.5 (41). Direct esterification can also be employed to impart alcohol solubility.Ethyl ester of hydrolyzed collagen (or other protein hydrolyzates) as a plasti-

158 Neudahlcizer in hairsprays will provide a harder, more lustrous film than the amine-neutralized fatty derivatives. As is typical for resin plasticizers, use level shouldnot exceed 10% of resin level. Silicone grafted protein hydrolyzates can impart improvements in wetcombing and feel from shampoos (42) and enhance deposition over that of theparent hydrolyzate as a result of peculiar solubility profiles (43).V. SKIN CONDITIONINGA. Enzymes Used in Skin ProductsThere is interest internationally in cosmeceutical-type skin care products con-taining enzymes (44). Superoxide dismutase, a superoxide radical scavengerwhich may thereby function as an antiinflammatory agent, has been protectedin gelatin microspheres, allowing the majority of the enzyme to be deliveredin active form from the preparations. This mode of entrapment improved sta-bility toward pH and temperature extremes as well as providing increased re-sistance to protease attack (45). Similar stabilization can be expected withother enzymes. Papain, a protease, has been immobilized on polyacrylic acidfor use as an alternative to AHAs as an exfoliant (46). Papain is active at pH5-7, allowing formulations at less extreme pH than is required for AHA-basedformulas. A composite of enzymes involved in the protection of various plantsfrom the effects of ultraviolet irradiation has been assembled for use as UVabsorbers and attenuators in topical skin care applications (47).B. CollagensThe natural protein choice for skin care applications is still collagen, as it isthe major structural protein in skin. Soluble collagen, a triple helix of 250,000to 300,000 Da, has strong moisture-binding properties without the tackinessthat can be associated with the use of amino acids as humectants. Incorpora-tion in moisturizing lotions and creams provides an elegant, silky, cushionedfeel to the skin and leaves the skin smooth, soft, and perceptibly moisturized.Applied medicinally, soluble collagen appreciably shortens the time for bumsand wounds to heal. To minimize degradation during storage, soluble collagen is best kept un-der refrigeration. To prevent denaturation during incorporation, it should beadded to finished products after emulsion formation and at no greater than30°C. Greatest stability is at near-neutral pH. Soluble collagen loses its effec-tiveness in formulations containing high levels of salt, alcohol, or surfactant,and urea, tannins, chloroacetic acid, formaldehyde, and other denaturing orcrosslinking agents. Low-salt (less buffered) versions are available for use inemulsions which are extremely salt sensitive.

Proteins for Conditioning Hair and Skin 1591. GelatinGelatin is a collagen hydrolyzate of about 150,000 Da. Such high molecularweight is possible despite a collagen monomer molecular weight of only 95,000Da because mature collagen has covalent crosslinks between monomers whichare not broken during heat-induced hydrolysis of the collagen. Gelatin findsuse as a natural viscosity builder and thickening agent. It also forms a protec-tive film on the skin and so acts as an antiirritant. Gelatin and its incomplete hydrolyzates (>700 Da) applied directly to theskin feel tacky and so require a balanced formulation to produce desirableesthetics. Formulations best employ a coarse mesh (6-10 mesh on U.S. sieves),as finer meshes wet out quickly, clumping easily to form \"fish eyes\" (dry gelatincores encased in partially hydrated lumps of gelatin). To keep this from hap-pening with finer meshes, high shear is required, often resulting in aeration ofthe batch. The optimal hydration temperature is thus 170-180T (77-82°C), acompromise between clumping from too rapid wetting at higher temperatureand excessively long hydration times at lower temperatures. Shortly after hy-dration is complete, the batch temperature should be reduced to retard ther-mally induced degradation of the gelatin.2. Hydrolyzed CollagenHydrolyzed collagen of 5000 to 15,000 Da in lotions and creams can functionas auxiliary emulsifiers, stabilizing emulsions, as well as enhancing the water-binding characteristics of the finished product, thereby slowing transepidermalwater loss (TEWL) upon application to the skin as a result of the protectivecolloidal film which forms. Hydrolyzed collagen of 2000 Da in lotions and creams can form moistureretentive films on the skin. Further, in surfactant systems it complexes withmonomeric anionic surfactant molecules, effectively raising the critical micelleconcentration of such systems, thereby reducing irritancy (13). At a 2-3% level inhand dishwashing liquids, a reduction in skin tautness following usage is observedas well (16). These hydrolyzates are also said to combat the dtying effects ofdetergents on skin via their protective colloidal film-forming properties (48,49).Soy and wheat protein hydrolyzates can be expected to perform comparably.C. Hydrolyzed ElastinHydrolyzed elastin of 2000 to 5000 Da is also a good film former, but is muchless hygroscopic due to its low polar and charged amino acid content. As aresult, it is effective in reducing TEWL and may be preferable to collagen (andother more hydrophilic hydrolyzates) where moisture-retentive and humidity-resistant features are desirable. Its high solubility in hydroalcoholic systemsallows its use in facial toners and aftershave liquids.

160 NeudahlD. Amino AcidsCollagen \"amino acids\" (amino acids to 700-Da polypeptides, depending onthe manufacturer) are highly hygroscopic and substantive to the skin, enhanc-ing moisture binding of products in which they are incorporated and so slowingTEWL. These low-molecular-weight hydrolyzates do not have the tacky feelof higher-molecular-weight hydrolyzates. Emulsions should be formed priorto the addition of collagen amino acids because of their high ionic strength.Wheat amino acids are of small size, allowing penetration of the skin's outerlayer, in a manner similar to that observed for hydrolyzed collagen, for mois-turization from within owing to their hygroscopic nature (21). Individual amino acids and derivatives are used for specific effects. Tyro-sine and derivatives find application in sun care products because of theirinvolvement in skin coloration processes, synthetic and natural. Gelatinglycine enriched with lysine was reported to reduce the irritancy of emul-sions containing 10% glycolic acid while enhancing recovery of skin elas-ticity and depigmentation of age spots (50). Use of acetyl cysteine was recentlypatented by Procter and Gamble as an alternative to alpha-hydroxy acids(AHAs) for the removal of dead skin. The method utilizes sulfhydiyl com-pounds such as this to improve skin suppleness and smoothness and to treatacne (45).E. Other i\/lodified ProteinsQuaternization of protein hydrolyzates increases their isoionic points, enhanc-ing substantivity and reducing the irritation of anionic surfactants in cleansingformulations (13). For example, polytrimonium gelatin (gelatin hydroxypro-pyltrimonium chloride) (51) reduced both the eye and skin irritation of a chlor-oxylenol-based antiseptic cleanser and propyltrimonium hydrolyzed collagenreduced irritation ratings from severe to nonirritating when one part wasadded to five parts sodium lauryl sulfate (38). Anionic hydrolyzates, produced from the grafting of fatty acid residueson primary amino groups, remain film formers. They are readily incorporatedinto solvent-based systems such as nail polishes and polish removers, andmay also be used in tanning oils to assist in their removal during subsequentskin cleansing. Neutralized forms (e.g., TEA-cocoyl hydrolyzed collagen)are low-irritation, relatively high-foaming surfactants (17) that are usefulin mild surfactant-based skin cleansing compositions such as facial washesand bubble baths. Further testing has been performed on specific \"lipoamino acids\" (anionichydrolyzates). Their amphophilic character facilitates transport across bio-membranes. They thus penetrate the skin to an extent and in a manner whichunderivatized amino acids cannot, penetrating the intercellular cement and

Proteins for Conditioning Hair and Skin 161contributing the regulation of water content of the skin from within. Toxicityand antigenicity are low, and some have the capacity to inhibit proteolyticenzymes such as elastase, urokinase, and plasmine (52). Palmitoyl hydrolyzedwheat protein was demonstrated to stimulate protein synthesis in human epi-dermal keratocytes in vitro at 0.1%, an effect which may have been nutritivein origin. Human dermal fibroblast cultures treated at 0.1 /ag/L with this com-pound produced greater extracellular matrix collagen fiber crosslinking, simi-lar to that observed with vitamin C, which would present itself in vivo as animprovement in the skin's elasticity and firmness. Using a gelatine cellsmethod, dose-dependent reduction in TEWL across an emulsion film contain-ing this material was demonstrated. An in-vivo soothing effect (a slight reduc-tion in skin redness versus a control) was demonstrated on abraded skin aswell.Vi. FUTURE TRENDSIn an era of formulation which has been defined by the concepts of renewableresources, natural derivation, environmental friendliness, biodegradabil-ity, irritation reduction, natural (plant) sourcing, volatile organic compound(VOC) reduction, and ecological soundness, nature-identical proteins andtheir hydrolyzates and derivatives are poised for increasing utility. The extentto which their potential is achieved will depend largely on the level of basicand applied research performed to generate and/or elucidate the propertiesdesired in the next generation of products. Selection of plant-derived protein products over animal-derived productsis likely to continue. While initially driven by the greater marketing appeal(and occasionally different performance properties) of plant-derived materi-als, the shift has been accelerated by concerns related to bovine spongiformencephalopathy (BSE) in the United Kingdom (53,54). Further, globalizationof raw material supplies and formulations requires accommodation of a sig-nificant portion of the world's population who find certain (or all) animal spe-cies, their biological components, and/or their by-products objectionable foruse in foodstuffs or elsewhere. Biotechnology, fermentation science, and genetic engineering are likely toyield highly functional materials for tomorrow. In hair care, proteins of cus-tomized amino acid content and configuration could be the polymers provid-ing flexible hold over a broad humidity range from a low-VOC matrix. Immo-bilized enzymes without antigenic potential may be applied to damaged hairto remove frayed cuticle, thereby enhancing shine, much as cellulases arecurrently utilized to remove fuzz from cotton clothing during laundering andthereby brighten colors. Modified amino acids could penetrate the cortex andconvert cysteic acid residues to moieties capable of forming disulfide bonds,

162 Neudahlthereby allowing strengthening of hair. Selected amino acids or polypeptidesor their derivatives may enhance the protective effects observed with wholeprotein hydrolyzates and may do so at a much lower use level, allowing appli-cation in permanent waving or relaxing systems which currently are intolerantof the ionic strength. Already a blend of fruit enzymes has been proposed asa total replacement for traditional surfactants in shampoo and bath applica-tions (55), and whey protein, with its activated cytokines [immunological regu-lators, signaling and controlling molecules in cell-regulating pathways (45)]has been shown in in-vivo human testing to improve skin firmness, touch, andsmoothness and to increase skin elasticity and thickness (56). Indeed, skin is likely to be the primary beneficiary of the next generationof protein-based products, despite regulatory roadblocks which may resultfrom their druglike effects. Perhaps the greatest untapped resource in the ad-vance of skin care lies in the delivery of functional enzymes through the epi-dermal barrier for the treatment of both \"cosmetic\" and physiological defi-ciencies. Advances in stabilization and delivery systems for macromoleculeswill make what was once an impossibility a reality. The first step, delivery of functional and stable enzymes to the skin's sur-face, has already been achieved through the use of two-component packaging:polyol-stabilized serine protease phase has been co-dispensed with an aqueousactivation phase to provide skin smoothing effects (20). Other proposed com-binations include a tocopheryl acetate phase co-dispensed with an esterase togenerate free tocopherol and a magnesium ascorbyl phosphate phase co-dis-pensed with a phosphatase phase to delivery free ascorbic acid (vitamin C).These proposals were given noting the potential for allergenicity and recom-mended attachment of enzymes to substrates of sufficient size to precludeinhalation, as well as proper safety evaluation (as respiratory allergenicity test-ing of formulations is not typical). Enzyme technology has also been refer-enced in the mitigation and prevention of adult acne (57). The next step will be the intentional delivery of active principles (which mayinclude enzymes, hormones, and specific polypeptides or amino acids, as wellas many other materials) to living skin cells for cosmetic purposes, with theaim of providing noticeably \"improved\" skin texture and topography. In prac-tice this occurs unintentionally when products which have been tested for per-formance on \"normal\" skin are utilized on excessively dry, burned, abraded,or otherwise compromised skin. Defects in the stratum comeum (and deeperlayers of the skin) allow substances to pass directly to the living cells and exertan effect. It also occurs intentionally when drug products are applied to relievepain, kill embedded microorganisms, fight acne, or otherwise promote theskin's well-being. Just as alpha- and beta-hydroxy acids and standardized bo-tanical extracts have pushed the limits of cosmetic versus drug, so these new

Proteins for Conditioning l-lair and Si<ln 163protein-based products will. Indeed, the deciding factor will likely be the claimsmade, not the results delivered. Envisioned is the use of liposomal or micellar vesicles to deliver activesthrough intact skin and the development and marketing of products for \"sen-sitive\" skin, including compromised skin. A cosmetic manufacturer's \"oil-con-trol hydrator\" has already featured an exclusive enzyme technology to helpnormalize skin to produce measurably less oil (57). Its intensive lifting cremeincludes an undisclosed restorative enzyme encapsulated in liposomes, andother manufacturers' products feature enzyme complexes for cell energy andglycoprotein to stimulate natural regeneration of the skin (58). Because products will rely on intimate contact with living cells to achievethe visible and tactile improvements desired, the microbiological and bio-chemical purity of proteins throughout isolation or manufacture will becrucial. If deleterious agents such as endotoxins (lipopolysaccharide-proteincomplexes of the outer membrane of Gram-negative bacteria which producerelease of pyrogens in mammals, resulting in fever) are present, a detrimentalresponse may be expected for the user (59). On the other hand, direct deliveryof a desired therapeutic material may have as rapid and pronounced a positiveeffect.ACKNOWLEDGMENTSThanks are expressed to each manufacturer's representative who kindly re-sponded to information requests, and particularly to Suellen Bennett (BrooksIndustries), Michael Birman (Croda, Inc.), Steve Bell (Hormel Foods), andAnna Howe (Inolex Chemical) for extensive literature made available. Thanksare also expressed to Alberto Culver USA (and Jo Rathgeber, Senior Re-search Librarian) for making library resources available, and to Ed McKeown(Costec, Inc.) for heartily encouraging and supporting this effort.REFERENCES 1. Lehninger AL. Proteins and their biological functions: a bird's eye view. In: Bio- chemistry, 2d ed, New York: Worth, 1977:57-70. 2. Perlmann GE, Manning JM. Proteins. In: McGraw-Hill Encyclopedia of Science and Technology. 6th ed. New York: McGraw-Hill, 1977,14:405-409. 3. Johnsen VL. Innovations in protein products and technology. Cosmet Toilet 1977; 92 (Dec.):29-36. 4. Gelatin. New York: Gelatin Manufacturers Institute of America, 1993. 5. Burmeister F, Brooks GJ, O'Brien KP. Vegetable/plant proteins in shampoos. Cos- met Toilet 1991 (Apr.); 106(4):41-46. 6. Bouthilet RJ, Karler A. Cosmetic effects of substantive proteins. Proceedings of the Scientific Section of the Toilet Goods Association 1965 (Dec); 44:27-31.

164 Neudahl 7. Stern ES, Johnsen VL. Studies on the molecular weight distribution of cosmetic protein hydrolyzates. J Soc Cosmet Chem 1977; 28:447-455. 8. Johnsen VL. Proteins in cosmetics and toiletries. Technical Services Report #8. Philadelphia: Inolex Chemical Company. 9. The effect of pH on the sorption of collagen-derived peptides by hair. Technical Services Report #19. Philadelphia: Inolex Chemical Company.10. Karjala SA, Williamson JE, Karler A. Studies on the substantivity of collagen-de- rived polypeptides to human hair. J Soc Cosmet Chem 1966; 17:513-524.11. Frowde HL. Hair Dyeing Method. U.S. Patent 3,193,465 (1965).12. Stern-Cooperman ES, Johnsen VL. Penetration of protein hydrolyzates into hu- man hair strands. Cosmet Perf 1973 (July):88-92.13. Tavss EA, Eigen E, Temnikow V, Kligman AM. Effect of protein cationicity on inhibition of in vitro epidermal curling by alkylbenzene sulfonate. J Am Oil Chem Soc 1986; 63(4):574-579.14. Wenninger JA, McEwen GN Jr. International Cosmetic Ingredient Handbook. 3d ed. Washington, DC: The Cosmetic, Toiletry, and Fragrance Association, 1995.15. Stern ES, Johnsen VL. Cosmetic proteins: a new generation. Cosmet Toilet 1983; 98(5):76-84.16. Croda Cosmetic and Pharmaceutical Formulary, Chapter 19 (Crotein), Parsip- pany, NJ: Croda, Inc., 1977.17. Promois Digest. Osaka, Japan: Seiwa Kasei Co., Ltd. 5th printing. May 1995.18. Cosmetic Ingredient Review, final report: safety assessment of hydrolyzed colla- gen, J Am Coll Toxicol 1985; 4(5):199-221.19. Verbent A. The fascinating challenge to mimic nature in producing recombinant glycoproteins. Chimica Oggi/Chemistry Today 1996 (Oct.); 14(10):9-14.20. Edens L, van der Heijden E, Delivery of enzymes and high actives in cosmetics. Cosmet Toilet Manufacture Worldwide 1997:189-193,21. Poppe CJ. Enriching the life of hair. Soap/Cosmet/Chem Specialties 1996 (Oct.); 72:28,30,32,34,36,40.22. Fed Reg 42:17109, March 31,1977 (FTC Ruling).23. Gehta-Proteins: Application in Skin-Care Products. Eberbach, Germany: DGF Stoess, July 1995.24. Hormel Foods Specialty Products Hydrolyzed Collagen. Brochure SP3812, Austin, MN, 1994.25. Peptein 2000, Soap, Perf Cosmet 1996 (Dec); 69(12):9.26. CO2 laser vanquishes skin wrinkles (temporarily). Biophotonics Int 1996 (Nov,/ Dec); 3(6):31-32,27. Crodata: Kerasol (A Unique Keratin Protein). Parsippany, NJ: Croda, Inc., July 9,1987.28. U.S. Patent 4,279,996 (1981), Keratin hydrolyzate useful as hair fixatives, assigned to Seiwa Kasei.29. U.S. Patent 4,390,525 (1981), Keratin hydrolyzate useful as hair fixatives, assigned to Seiwa Kasei.30. Plantasol W 20 Product Information. PIW20-8E. Eberbach, Germany: DGF Stoess. Oct. 1995.

Proteins for Conditioning Hair and Skin 16531. The compounder: sweet almond derivative helps produce healthy hair. Drug Cos- met Ind 1996 (Aug.); 159(2):55.32. Crodata DS-31R-1: Cropeptide W. Parsippany, NJ: Croda, Inc., July 6,1994.33. Peptein WPO. Document 09-058-5790. Austin, MN: Hormel Foods Specialty Products, Oct. 1996.34. Hydrolyzed Oat Protein HOPA Data Sheets. Saskatoon, Saskatchewan, Canada: Canamino, Inc., 1996.35. Hydrotriticum WAA. Drug Cosmet Ind 1996 (Aug.); 159(2):5.36. Crodata DS-27R-1: Hydrotriticum WAA. Parsippany, NJ: Croda, Inc., June 1, 1994.37. U.S. Patent 4,793,992 (1988), Hair treatment composition, assigned to Redken Laboratories, Inc.38. Protectein Data Sheet. Document 09-008-5790 Revision D. Austin, MN: Hormel Foods Specialty Products, Dec. 1995.39. A Guide to Formulating Protein Hair Care Products. MGL6003. University Park, IL: Mclntyre Group Ltd. Aug. 1995.40. Crodata DS-19R-1: Hydrotriticum QL, QM and OS. Parsippany, NJ: Croda, Inc. June 10,1994.41. Foam-Colls Technical Data 1070/2. South Plainfield, NJ: Brooks Industries. Sept. 1990.42. Promois SIG Series Technical Data Sheet. Osaka, Japan: Seiwa Kasei Co., Ltd., Apr. 22,1995.43. Crodata DS-39R-2: Crodasone W. Parsippany, NJ: Croda, Inc., Sept. 10,1996.44. Shaw A. International Cosmetics Report. Soap Cosmet Chem Specialties 1996 (Oct.); 72:46.45. Fox C. Technically speaking. Cosmet Toilet 1996 (Sept.); 111(9):15,16,19,20.46. New chemicals for specialties: AHA ahernative. Soap Cosmet Chem Speciahies 1997 (Feb.); 73(2):107.47. Campo Research Plants' UV protectant active principle(s) \"UVzymes.\" House- hold Personal Prod Ind 1997 (May); 34(5):30.48. U.S. Patent 3,548,056 (1970), Eigen E et al., assigned to Colgate-Palmolive Com- pany.49. U.S. Patent 4,195,077 (1980), Detergent Compositions Comprising Modified Pro- teins, assigned to The Procter & Gamble Company.50. Goldemberg RL. The compounder/compounder's corner. Drug Cosmet Ind 1997 (May); 160(5):66-67.51. Data 1045: Quat-Coll IP-10 (30%). South Plainfield, NJ: Brooks Industries, Inc., Fall 1992.52. Michel N. Stoltz C. The interest of amino acid biovectors. Drug Cosmet Ind 1996 (Sept.); 159(3):36-38,40,42,104.53. Shepherd T. Rendered products market post March 96. Oils Fats Int. 1996; 12(6): 36.54. Regulations: a new EU ban on British gelatin? Household Personal Prod Ind 1997 (May); 34(5):40.55. Natural ingredients listing, Campo Research. Household Personal Prod Ind 1997 (June); 34(6):70,72.

166 Neudahl56. MFC—milk peptide complex. Soap Perf Cosmet 1996 (Dec); 69(12):26.57. Colwell SM. Clearly in demend. Soap Cosmet Chem Specialties 1997 (Feb.); 73(2): 32-34,36,38.58. Dunn CA. The skin care market. Household Personal Prod Ind 1997 (May); 34(5): 79,80,82,84.59. Held DD, Mehigh RJ, Wooge CH, Crump SP, Kappel WK. Endotoxin reduction in macromolecular solutions: two case studies. Pharmaceut Technol 1997 (Apr.); 21(4):32,34,36,38.

8Organo-Modified SiloxanePolymers for ConditioningSkin and HairEric S. AbrutynThe Andrew Jergens Company, Cincinnati, OhioI. BASICS OF ORGANO-MODIFIED SILOXANE POLYMERSA. HIstorial PerspectiveIn general, the term silicone is used to describe organo-modified siloxanes—mentioned by Kipping in 1901 and based on the generic formula R2SiO—^whereR is CH3 (polydimethylsiloxane, PDMS) and R2SiO is referred to as a siloxygroup. Two well-known types of silicones are cyclomethicone and dimethicone.Organic groups attached to a siloxy group (e.g., alkyl, phenyl, polyether, tri-fluoropropyl, vinyl), in turn create organo-siloxane polymers which have physi-cal properties of the \"inorganic\" siloxane backbone (silicon-oxygen-silicon,Si-O-Si) and the \"organic\" group attached to it. These organo-modified silox-ane polymers have unique properties that make them very useful in personalcare products. The basic raw material from which silicones are formed is quartz, i.e.,silica or silicon dioxide (Si02). In the form of crystals or fine grains, quartz isthe main constituent of white sand. In 1824, Jons-Jacob Berzelius, a Swedishchemist, was successful in liberating elemental silicon (Si) from quartz by re-duction of potassium fluorosilicate with potassium. Alkylation of elementalsilicon to prepare alkyl silanes was done initially by Friedel and Crafts (1863) 167

168 Abrutynusing zinc compounds, by Kipping (1904) using organo-magnesium compounds(Grignard reaction), and independently in the 1930s by Hyde (Coming GlassWorks) and Rochow (General Electric) using methyl chloride. These scien-tists synthesized the silicon-carbon bond—one of the most important steps inthe history of organo-siloxane polymer development (1,2). The silicon-oxy-gen-silicon backbone was synthesized by Ladenburg in 1871 by hydrolyzingdiethyldiethoxysilane in the presence of a dilute acid to form an oil (silicone).Between 1899 and 1944, Kipping published 54 papers on the subject of siliconchemistry, describing the first systematic study in the field. This work helpedHyde and Rochow develop a commercial process—\"the direct process\"—using elemental silicon and methyl chloride to produce organo-silicon com-pounds. Current reviews of the synthesis of organo-siloxane polymers havebeen written by Colas (3) and Rhone Poulenc (4).B. Polymer ManufacturingThe great diversity of functional siloxanes, which can be obtained from a rela-tively few silicon-containing monomers, may best be understood by consider-ing the chemistry of these monomers and their many possible combinations.As mentioned earlier, this process begins with high-grade quartzite rock thatis heated with charcoal in an electric furnace to produce elemental silicon ata purity of 98-99%; with heat, the carbon combines with the oxygen from thesilica. Extracted silicon is ground to a fine powder and induced to react withmethyl chloride gas at 250-300°C in what is called the direct process (5),producing several important chlorosilane monomer building blocks—mono-chlorotrimethyll silane, di'chlorodimethyl silane, trichloromethyl silane andtetrachloro silane. These compounds are fractionally distilled as purified chlo-rosilane monomers. Organo-modified siloxane polymers are derived from chlorosilane mono-mers via hydrolysis and polymerization and/or polycondensation. The hy-drolysis and condensation product of dichlorodimethyl silane is of particularimportance [(Me2SiO)x], as it is the major component of most organo-siloxanepolymer fluids and elastomers. When two or more types of functionalchlorosilanes are hydrolyzed together, the process is called co-hydrofysis. Anexample is co-hydrolysis of monochlorotrimethyl silane and dichlorodimethylsilane to form trimethyl siloxy end-cap polydimethylsiloxane chains. The re-sultant polymers from co-hydrolysis may be fluid, gel, crystalline solid,or resin, depending on the average functionality of the monomer—[(CH3)„SiO(4^y2jt. If n > 2, the product is a fluid; if n equals 2, the product isa cyclic or linear siloxane fluid (a gum, if a high-molecular-weight siloxane);and if n < 2, the product is a resin.

Organo-Modlfled Slloxane Polymers 169C. Polymer NomenclatureToday's nomenclature system (6) for organo-silicon polymers is based onSauer's (7) recommendations. These recommendations were subsequently de-veloped and adopted by the American Chemical Society (8), the Journal of theChemical Society (9), and lUPAC (10). In general, organo-silicon nomenclature is applied to any structure contain-ing at least one silicon atom. Silanes (R4Si) are silicon-containing compoundswith one silicon atom and four directly bonded groups. Silicones, containingalternating silicon and oxygen atoms, are cyclic, linear, branched, caged, orthree-dimensional polymers of the monomeric siloxy group. The prefix to thesesiloxane polymers designates the number of silicon atoms in the polymer—thatis, disiloxane has two silicon atoms, while trisiloxane has three silicon atoms,etc. Siloxanes and silanes are named similarly; the root describes whether it isa siloxane (Si-O-Si backbone) or silane (only one Si atom), and the organo-functional portion describes the type and amount of substitution: hexamethyl-disiloxane, decamethylpentacyclosiloxane, Tris(trimethylsiloxy)silane, and(poly)dimethylsiloxane. Shown below is a shorthand nomenclature of the four major organo-siloxychain units—M, D, T, Q. Each Si-0 bond has another Si attached through anoxygen linkage. Therefore, the mono-, di-, etc., refers to the number of poly-mer propagating oxygen bonds on Si.As an example using this shorthand nomenclature system, (poly)dimethyl-siloxane, containing 10 repeating dimethylsiloxy groups and terminated withtrimethylsiloxy groups, would have a shorthand description of MD10M. Addi-tionally, the T structure above represents silsesquioxane (e.g., the simplestform is M3T) and the Q structure represents silicate (e.g., the simplest form isM4Q).D. Chemical-Physical PropertiesThe unique structure of the basic organo-modified Siloxane polymer accountsfor the fundamental properties and resulting benefits to the personal careindustry (11a, l1b). A few fundamental chemical properties (12) that makeorgano-modified Siloxane polymers versatile are:

170 Aboxtyn 1. Si-C bond—low energy (75 kcal/mol) and long length (1.88 A), Si-O bond—low energy (106 kcal/mol) and long length (1.63 A) (13) means reduced steric interactions. 2. natter Si-O-Si bond angle (130-150\") versus C-O-C (105-115°) (14). 3. Lower energy of rotation that results from Si-O longer bond length and flatter bond angles. 4. Lower silicon electronegativity (1.8) than carbon (2.5), which leads to a very polarized Si-O bond that is highly ionic. 5. Low intramolecular and intermolccular (van der Waals) forces. These chemical properties, in turn, help explain some of the physical prop-erties (e.g., easy diffusion of organic molecules through organo-modified silox-ane films, low-tempcraturc stability, water repellency, and low surface ten-sion) of organo-modified siloxane fluids. For an understanding of the physical properties of organo-modified silox-ane compounds, one needs to understand the molecular architecture (15) ofsilicon-oxygen and silicon-carbon compounds compared to organic carb-on-carbon and carbon-oxygen compounds. Low bond energy and low bondrotational energy contribute to a high degree of rotation of a Si-O-Si back-bone. This freedom of rotation leads to a unique flexibility of a siloxanc mole-cule. A siloxanc molecule can be compared to a spring, Slinky, or accordion as itsrelates to back-and-forth and twisting motion. This bond flexibility is an importantaspect of organo-siloxanc polymers. It is believed that the freedom of rotationof a Si-O-Si backbone allows for an organo-cloud orientation [see Figure 1 (16))that facilitates an effective spatial orientation/alignment at the interface of thesurface to which an organo-siloxane polymer is exposed (lines A and B inFigure 1 represent interfaces). This freedom of rotation allows for maximizingsurface activity, aligning the inorganic backbone (high-surface-encrgy Si-O-Sibackbone) to high-polarity surfaces (line B in Figure 1) and organo-groups(low-surfacc-cnergy CH3 groups) to low-polarity surfaces (line A in Figure 1). The spatial orientation of nonpolar methyl groups (as represented by CH3in Figure 1), with their low surface energy—measured as lower interfaceFigure 1 Organo-cloud orientation of a (poly)dimcthylsiloxanc molecule.

Organo-Modified Siloxane Polymers 171tension—yields an interface which can be characterized as organic and hydro-carbon-like. These methyl groups, with low intermolecular forces and surfaceenergy, are inert and hydrophobic. The flexibility of the Si-O-Si backboneallows for the maximization of hydrophobicity and surface activity attributesof the methyl groups. Due to the packing of methyl groups at a surface, thesurface tension is very low. The low surface tension of PDMS fluids (PDMS,20 dynes/cm; cf. benzene, 28.9, and water, 72) permits them to spread easilyover surfaces, which, coupled with other properties (e.g., low coefficient offriction), translates to silky, smooth, nontacky esthetic qualities. The intra/intermolecular forces are low between siloxane molecule(s),giving rise to low resistance to flow when stressed, creating the ability toengineer high-molecular-weight polymers with relatively low viscosities.The glass transition temperature {Tg) of (poly)dimethylsiloxane is low, at—120°C (flowable liquid down to the Tg). Polymers with molecular weight{MN) as high as Vi million are still fluids—a unique distinguishing point com-pared to similar molecular-weight organic polymers. At the same time, chang-ing the structure of organo-modified siloxane polymers allows for physicalform differences, e.g., from waterlike-viscosity volatile siloxanes to rubberlike,and even glasslike siloxane resins. The resultant physical property data onorgano-modified siloxane compounds have been referenced in many sources(17). Siloxane chain entanglement also plays an important role in solvation andflow. Ferry (18) characterized the relationship of viscosity and molecularweight (M„ oc Ti). Below 1000 cP viscosity for PDMS, viscosity and molecularweight are more nearly proportional—thus, viscosity is increasing at a corre-sponding rate to M„. Above 1000 cP, viscosity is not proportional to molecularweight—^viscosity increases nearly 3.5% faster than M„. This can be explainedusing the \"reptation\" model (molecules are moving through the mass by pull-ing in and out through tunnels). If one thinks of a mass of worms (eachworm—strand—is a PDMS molecule), it takes time for the strands to slidein and out. With branching or crosslinking, the constraint on flow is dramati-cally slowed and viscoelastic properties play a stronger role. Thus, withcrosslinked or high-molecular-weight PDMS, solvents can swell but not dis-solve the molecules, time and energy being required to solvate and disentanglethe molecules.E. ClassificationThe silicone family of products is extensive. The silicon atom has the ability toaccept many different substituents, and the siloxane backbone can take ondifferent structures, which then create the opportunity to change the physicaland, as a result, the performance characteristics of functional silicones from:

172 Abrutyn AmodimetliiconeFigure 2 Pictorial of silicone family of products. Volatile -> range of viscosity -> high-melting-point wax Defoamer -> profoamer -> emulsifier Fluid -> elastomeric -> resinous powder.Figure 2 shows a pictorial representation of the silicone family of products—dimethyl, alkyl, aromatic, polyethers, amino, and three-dimensional—that arecommercially available and commonly used in the personal care industry. What follows is a more in-depth look at some key functional Siloxane prod-uct families.1. (Poly)dimethylcyclosiloxanesThe most common (poly)dimethylcyclosiloxanes [International NomenclatureChemical Ingredient (INCI): Cyclomethicones] possess 6, 8,10,12, or 14 at-oms in their ring structures (Figure 3) with 3 silo)^ bonds (INCI: Ciyclotrisiloxane),4 siloxy bonds (INCI: Cyclotetrasiloxane), 5 siloxy bonds (INCI: Cyclopenta-siloxane), 6 siloxy bonds (INCI: Cyclohexasiloxane), and 7 siloxy bonds (INCI:E CH3 , - Si - 0 J, CH3where n = 3,4,5,6, etc.Figure 3 Empirical structure of C-PDMS (cyclomethicone).

Organo-Modifled Slloxane Polymers 173Table 1 Heat of Vaporization of Common Personal Care CarriersMaterial Heat of vaporization (cal/g)Water 539Ethanol 210Cyclotetrasiloxane 32Qfclopentasiloxane 32Cycloheptasiloxane), respectively. Volatile (poly)dimethylcyclosiloxanes areconsidered non-Volatile Organic Components (VOC) as regulated by the U.S.federal (19) and state Environmental Protection Agencies (EPA). Cyclometh-icone fluids have unique physical properties that translate into benefits forpersonal care applications. These include volatility, low viscosity, and non-residual transient skin feel. Cyclomethicone fluids have low heat of vaporiza-tion (Table 1), they are noncooling (i.e., cooling during evaporation from skinis minimal), and are nonstinging—a combination rare for personal care carriers.Other attributes of cyclomethicone fluids include: colorless, odorless, non-staining, good spreading, detackification, water sheeting, and transient emol-liency properties. The level of use of cyclomethicone in personal care applica-tions is typically from 0.1% to 85%; the low end represents use levels whichenhance skin feel in creams (e.g., hand and body moisturizers), and the high-end use levels are to carry actives to skin and hair (e.g., antiperspirant salts,hair cuticle coat). Another aspect of cyclomethicone fluids that make themfunctional in the personal care industry is that they have broad compatibilitywith most personal care ingredients, including ethanol, mineral oil, and fattyacid esters. Another key attribute ot cyclomethicones is their ability to provide appeal-ing sensorial esthetics to personal care products. Key sensorial estheticstypically associated with (poly)dimethylcyclosiloxanes, of which cyclopenta-siloxane is a good example, are low residue, low stickiness, low tackiness,low greasiness, and low waxiness. Using a protocol developed by DowCorning Corporation (20) in Figure 4 one sees that cyclopentasiloxane hassensory properties normally associated with silicones. The scale in Figure 4that is used to rank each attribute is based on 0 to 10, with 10 representing themost and 0 representing the least for the attribute measured. As the ring sizeof (poly)dimethyl-cyclosiloxane changes, there are minor changes in sensoryeffects. Larger-ring-size cyclomethicone fluids are slower to volatilize, andthey reside on the skin longer to give a longer-lasting feel until they totallyevaporate.

174 AbrutynFigure 4 Cydotctrasiloxanc sensory profile.2. Linear (Pofy)dimethylslloxanes (Dimethicone and Dimethiconol)Linear (poly)dimethylsiloxane (INCI: Dimethicone)—see Figure 5—havingtrimcthyl end blocking, can have from two to thousands of repeating dimethyl-siloxy groups (Figure 5a), with viscosities ranging from 0.65 to > 100,000 ccn-tistokes (cS) (Table 2). When linear (poly)dimethylsiloxanes are hydroxy ter-minated, they are called dimethiconols (INCI), which have viscosities as highas 30,000,000 cS (Figure 5b). where m it gretter thin 0Rgura 5 Empirical structure of (a) linear pofy(dimcthylsiloxane) and (b) dimcthi-conol.

Organo-Modlfied Slloxane Polymers 175Table 2 Comparative Molecular Weights for Different Viscosity (Poly)diniethyl-siloxanesAverage Approximate No. of Example ofviscosity (cS) molecular subunits similar weight (MD.M) viscosity 5 800 9 Water 20 2,000 27 Cooking oil 50 3,800 50 Paint 100 6,000 80 Shampoo 200 9,400 125 Mineral oil 185 Ketchup 350 13,700 230 Motor oil 500 17,300 375 Corn syrup 1,000 28,000 665 Molasses 5,000 49,300 845 10,000 62,700 910 Honey 12,500 67,700 1,235 Hot tar 30,000 91,700 1,570 60,000 116,500 1.875 Thick milkshake 100,000 139,000 2,750 Petroleum jelly 300,000 204,000 3,510 Silly putty 600,000 260,000 5,400 4,000,000 400,000 7,43020,000,000 550,000 As a class of personal care additives, linear PDMS is considered a goodskin emollient and lubricant. Linear PDMS generally acts as (a) skin-feel mod-ifiers, (b) water barrier protectants, (c) defoamers, (d) desoapers (i.e., eliminatorsof creamy whitening of a cosmetic formulation during the initial rubbing ontoskin or hair), and (e) providers of conditioning and emoUiency. Dimethicone is covered in the \"Skin Protectant Monograph\" as an over-the-counter drug (21) and is listed in the National Formulary compendium(22). Because dimethicone can be recognized as a drug, when sold under acompendia name with skin protectant claims it must meet the requirements asoutlined in the compendium, and the substance's name must be distinguishedclearly on the label. The tentative final monograph identifies which active canbe used at use levels of 1-30% as an active ingredient in OTC products withlabel claims such as \"helps prevent and temporarily protects chafed, chapped,cracked, or windburned skin and lips.\" Linear PDMS is noted for its thermal and oxidative stability over a widerange of temperature. When held in contact with air at 150°C, linear PDMS

176 Abrutynis stable for long periods. These compounds oxidize at higher tempertaures,well above those typically associated with operating temperatures used in thepersonal care industry. In the absence of oxygen and at temperatures above250°C, linear PDMS can be broken down to smaller polymers. This breakdownprocess is known as depolymerization (a phenomenon similar to the crackingof petroleum). Additionally, the low glass transition temperature (Tga -120°C)of PDMS means that the polymers are flowable liquids down to that Tg. It is the compatibility (solubility) characteristics of linear PDMS that con-tributes to its unique esthetics and film-forming properties. Because linearPDMS has limited compatibility in typical cosmetic ingredients, it tends tomigrate to the surface (away from the skin or hair). The compatibility of linearPDMS varies with its viscosity—^with the low-viscosity fluids having compati-bility with more materials than higher-viscosity fluids. Linear PDMS is insol-uble in water, but soluble in aliphatic hydrocarbons, aromatics, and chlorinatesolvents (e.g., hexane, toluene, methylene chloride, and chloroform). Further-more, linear PDMS is incompatible in mineral oils and solvents such as iso-propanol; lower-viscosity PDMS has greater miscibility, especially in mineraloils and solvents such as isopropanol. Volatility and vapor pressure decrease while viscosity and molecular weightincrease for linear PDMS. Hexamethyldisiloxane (0.65 cS) possesses the high-est volatility of linear or cyclic (poly)dimethylsiloxane fluids—similar to etha-nol. PDMS starts to lose its volatility at about 5 cS (around 800 molecularweight). Volatile PDMSs are classified as non-Volatile Organic Components(VOC) as regulated by the U.S. Environmental Protection Agency (23) andindividual state governments. When linear PDMS fluids are incorporated with cosmetic ingredients tomake a personal care product, sensory attributes may be slightly differentcompared to the neat PDMS fluid. The ease of spread and lubricity of alinear PDMS fluid produces the characteristic velvetlike feel typically associ-ated with silicones. As the molecular weight increases for linear PDMS, anincrease in residue, oiliness, and smoothness can be observed. Figure 6denotes the sensory attributes for a medium-viscosity linear PDMS (350cS)—sensorial attributes are evaluated by trained sensory panelists. In Figure6 one sees an increase in residue, oiliness, greasiness, and waxiness of 350-cSdimethicone, a linear PDMS, compared to cyclomethicone (reference Figure4). Dimethicone, 350 cS, shows different attributes than cyclomethicone, be-cause it does not volatilize and thus remains on the skin. To effect a perceived sensorial change in a personal care product, onewould usually need to use between 0.1 and 5% of a linear PDMS fluid. Figure7 shows the minimum threshold levels required for various PDMS polymersbefore they are judged as perceptibly different. As the molecular weight of

Organo-Modined Slloxane Potymert 177Figure 6 Sensory profile of 350 cS linear (poly)dimcthylsiIoxane.Figure 7 Threshold level of various PDMSs.

178 Abrutynlinear PDMS increases, a lower weight percent will be needed in formula-tions—the hypothesis is that a thicker film is produced—to effect perceivedsensory change, in particular, residue, oiliness, and smoothness. What can beconcluded is that, to elicit a sensory perception, (a) typically less linear PDMS(dimethicone) is required than cyclomethicone; and (b) as viscosity (molecularweight) increases, less linear PDMS is required.3. Other Functional Siloxanes a. Pofyether Functional (24). Polyether functional siloxanes (SPE, siloxanepolyether) are created by replacing some of the methyl groups on the siloxybackbone with polyether (polyoxyalkylated) substituents (see Figure 9, be-low)—^primarily ethylene oxide and propylene oxide. Substitution of a polyoxyalkysubstituent for a methyl group on the PDMS backbone results in a change in thehydrophile/lipophile balance (HLB) of a SPE polymer. Addition of polyethergroups allows for modification of compatibility of SPE polymers in polar andnonpolar solvents. Not only do polyether groups effect solubility, but also inter-facial tension characteristics of polyether functional siloxanes are different fromthose of comparable-molecular-weight PDMS. Polyether functional siloxanes can range from water soluble to oleophilicsoluble, thus having applications in both water and oil phases of cosmetic for-mulations. Water and polar solvent solubility increases when the mole percentand molecular weight of the polyoxyethylene moiety is increased. Completewater solubility occurs when the mass ratio of polyoxyethylene to dimethyl-siloxy groups is in the range of 2-4. They can be used to detackify water andoil phases of cosmetic formulations. High-HLB polyether functional siloxanesare used for detackification of water, and low-HLB polyether functional silox-anes are used for oil phases. Polyether functional siloxanes are playing an ever-increasing role in thepersonal care industry as emulsifiers [Silicone Formulation Aids® (25)] forwater-in-poly(dimethylcyclosiloxane) and water-in-oil emulsion. Their unique-ness as siloxane emulsifiers is due to flexibility of the siloxane backbone, whichin turn provides for reduction of interfacial tension, more effective surfacecoverage, and a thick phase between the water and oil phases without tem-perature or shear as the driving force (26). The stability of oil-continuous-phase (water-in-oil) emulsions is the result of a film of high viscoelasticity atthe water-oil phase boundary (27) of the emulsion. Polyether functional siloxanes provide advantages in producing water-in-poly(dimethylcyclosiloxane) and water-in-oil emulsions: (1) low levels ofemulsifier—less than 2%, but usually less than 1%; (2) creation of emulsionsthat vary in viscosity from pumpable fluids to extrudable gels to sticks (usingphase volume to control viscosity), and from opaque to crystal clear (usingrefractive index matching of the water and oil phase)—^without the need for

Organo-Modlfied Slloxane Polymers 179Figure 8 Empirical structure of phenyl trimethicone.making significant modifications in phase compositions; and (3) nonirritationor drying of skin. In addition to being efficient water-in-oil or water-in-(poly)dimethylcyclosiloxane emulsifiers, SPE polymers can enhance percep-tible skin feel in personal wash applications [e.g., bar soaps, shower gels (28)],act as good hairspray resin modifiers (29), and mild conditioners for clearshampoo. Also, it has been reported that certain water-soluble polyether func-tional siloxanes (30) can reduce eye irritation in shampoos. b. Phenyl Functional. Replacement of some methyl groups on a PDMSsiloxane backbone with phenol substituents results in an increase in the refrac-tive index (imparting shine or sheen), and broadened compatibility in comonpersonal care systems. Phenyl groups also enhance thermal stability, oxidativeresistance, and nonwhitening and nonresidue attributes (31). Figure 8 showsthe empirical structure of a phenyl functional siloxane, Phenyl Trimethicone(INCI). c. Alkyl Functional (32). Substituting alkyl groups (six or more carbons) forsome methyl groups on a PDMS siloxane backbone results in an alkyl func-tional siloxane (more specifically, alkyl methyl siloxanes or AMS). Alfcyl func-tionality of these siloxanes improves occlusivity (33) (decrease in water per-meability) and compatibility in common personal care systems. AMS polymershave product forms ranging from fluids to very-high-melting-point waxes (aboveWC). Alkyl substitution results in the modification of sensory characteristicsof a PDMS siloxane, providing esthetics approaching both hydrocarbons andsilicones—that is, a waxier and greasier feel during rub-out and a \"silicone\"smooth after-feel. AMS waxes have been reported (34) to provide bodyingand cushioning to all types of emulsions, with moisturization comparable topetrolatum. d. Amino Functional. The addition of aminoalkyl groups to a PDMSsiloxane backbone increases substantivity (35,36) of silicones. The most widelyused amine group is based on the ethylene diamine structure. Aminefunctional siloxanes can be trimethyl siloxy or dimethyl hydroxyl siloxy end-

180 Abmtynblocked. Typical INCI names assigned to this class of materials are Amodi-methicone, Amodimethiconol, and Trimethylsilylamodimethicone (see Fig-ure 9). Amine functional siloxanes can differ in length of siloxane backbone,linear versus branching of the siloxane backbone, substitution amount andtype of amino groups on the backbone, and the linking group on the aminomoiety. The addition of an amine group to a siloxane backbone allows forexcellent hair conditioning for both leave-in and wash-off conditioners. Amino-functional PDMS polymers can potentially cause skin irritation; therefore,caution is required when using them as skin conditioners. e. Crosslinked Poly(dimethylsiloxanes). This group of PDMS polymersis based on crosslinking of siloxane backbones. INCI names are Silicates(\"Q\" structures), Silsesquioxane (\"T\" structure), Crosspolymer, and Copoly-mer. Changing the degree of crosslinking of the PDMS backbone results in achange in the physical form from a soft gel to a glasslike solids. Recent patentshave been issued outlining the ability to modify rheology of functional silox-anes with crosslinked PDMS polymers (37-40). These patents show how toimprove appearance, bodying, cushioning of cosmetic products, and set reten-tion/styling of hair. Also, it has been speculated that crosslinking of the PDMSbackbone could improve substantivity without adding heaviness to resultantfilms. / Beyond Classical PDMS. How functional siloxanes are delivered to skinand hair is as critical as the structure/properties of the specific functional silox-ane. As an example, functional siloxanes can be added directly to a formula-tion and delivered to specific skin or hair sites as a solution or dispersion ofthe formula—requiring transport through the formula matrix to reach the de-sired location. Functional siloxanes can be predispersed as colloidal systems(e.g., emulsions and microemulsions) for ease of incorporation. Engineeringthe PDMS colloidal systems—particle size distribution, polymer rheology, andsurfactant type—can affect how other functional conditioners are delivered tohair and skin. Further, blending of functional siloxanes can provide the oppor-tunity for synergistic enhancement of performance.

Organo-Modlfled Slloxane Polymers 181 The above functional siloxane classifications and benefits for skin and hairconditioning are based on a simplistic view of the organo-modified siloxanebackbone. One can visualize the potential for significant changes in propertiesand the resultant benefits when the backbone is further modified (e.g., com-bination of functionality on the backbone, or reaction product of active siteson the functional attached moiety to the PDMS backbone. New, evolving mul-tifunctional siloxanes are covered by O'Lenick in Chapter 9 in this book.II. ORGANO-FUNCTIONAL SILOXANES FOR SKIN CONDITIONINGSilicones have been used to condition skin since the 1950s. Conditioning in thiscontext means beautification and esthetic improvement of skin, perceived byconsumers as resulting in healthy skin. Silicones provide these two benefits bynature of the chemical and physical properties of the siloxane backbone. Sili-cones act as excellent emollients (41) to provide perceived smoothness, soft-ness, and lubrication to the skin as delivered from personal care topical skinapplications. Film-forming characteristics of PDMS polymers provide uni-form deposition, self-healing films, and substantivity to skin. Increasing the compatibility of a blend of PDMS polymers and an or-ganic cosmetic ingredient may decrease spreading and film forming of theblend. This is because molecules can more easily co-mingle, and are lesslikely to migrate to the interfacial surface zone, where they would providelubrication. Organo-functional siloxane polymers are used in a variety of facial and bodycleansing applications (42). Volatile (poly)dimethylcyclosiloxane fluids areused extensively in nonrinsable makeup removers and cleansers, as they aregood solvents for organic-based oils, leaving skin with a dry, smooth, nongreasyfeeling. Also, they are mild and nonirritating to the skin. (Poly)dimethylsilox-ane fluids, such as dimethicone, polyether functional siloxanes, and amino-functional siloxanes, have been used in bar soaps to aid mold release and im-prove foam quality. As with 2-in-l conditioning shampoos, PDMS polymersare emerging in the shower gel market because consumers perceive them tohave a residual smooth after-feel. New developments in water-soluble (poly)dimethylsiloxane polyether tech-nology enable formulation of facial washes with improved stable foams andafter-feel characteristics, along with potential for reduced eye and skin irrita-tion. By reducing the surface tension of water, they become easier to spread.Also, polyether functional siloxanes, especially those with relatively high HLB(greater than 5), have benefits in surfactant-based systems by leaving a per-ceivable softness to the skin.

182 AbrutynA. Formulation ExamplesThe following formulas exemplify the use of silicones in personal care appli-cations as conditioning agents.1. Daytime Hand and Body Skin CreamFormula 1 demonstrates the use of cyclomethicone and dimethiconol (a blendof 13% high-molecular-weight PDMS polymer gum in cyclomethicone) to en-hance the non-oil feel during application of cream to the skin. After the for-mula dries, resultant smooth skin feel is associated with residual dimethiconol.Also, dimethiconol at a very small level (0.45%) provides a smoother and drierfeel during application of the cream on the hand and body.Formula 1 Hand and Body Skin Cream (43) 84.7% 0.1Water 3.0Carbomer 934 0.9Glycerin 1.0TriethanolamineCetyl Alcohol 0.8Stearic Acid 1.5Glyceryl Stearate 3.0Cyclomethicone (and) Dimethiconol 1.5Isopropyl Myristate 1.5Diisopropyl Adipate 2.0Mineral Oil q.s.Preservative/Fragrance CH3 CH3R(CHj)j(l^iO), (^iO), SJ(CH3)jR C'H 3 i 'w here: R - O H or (C H 3) R'= (CHj). NHCHjCHjNHiFigure 10 Empirical structure of amodimethicone.

Organo-Modlfied Siloxane Polymers 1832. Nighttime Skin LotionFormula 2 demonstrates how silicone emulsifiers (dimethicone copolyol,Figure 10) can be utilized to make simple water-in-cyclomethicone emulsionlotions that have an elegant after-feel (associated with dimethiconol). Eventhough polyether functional siloxane emulsifiers are not noted as conditionersof hair and skin, they provide unique and efficient delivery systems for otherconditioning agents.Formula 2 Nighttime Skin Lotion (44) 10.0% 10.0Cyclomethicone (and) Dimethicone Copolyol 10,0Cyclomethicone (and) Dimethiconol 0.5Cyclomethicone 62.5PPG-3 Myristyl Ether 5.0Water 2.0GlycerineSodium Chloride3. Contemporary Cold CreamFormula 3 demonstrates how silicone emulsifiers can be utilized to make sim-ple water-in-cyclomethicone emulsion creams that can remove makeup (dueto cyclomethicone) and have an elegant, low-residue skin feel.Formula 3 Contemporary Cold Cream (45) 10.0% 10.0Cyclomethicone (and) Dimethicone Copolyol 5.0Cyclomethicone 1.5C12-15 Alcohols Benzoate 1.5PPG-3 Myristyl Ether q.s. to 100%Sodium Chloride q.s.WaterPreservative4. Facial CieanserFormula 4 demonstrates the use of polyether functional siloxane (Dimethi-cone Copolyol) to add a soft feel during application and after. Choosing theright functional siloxane can also contribute to foam boosting and elegance ofthe foam structure as is demonstrated in this formulation.

184 AbrutynFormula 4 Facial Cleanser (46) 60.5% 12.0Water 10.0Disodium Cocoamphiodiacetate 8.0Sodium LauroyI Succinate 4.0Cocamidopropyl Betaine 0.5Lauramide DEA 5.0Citric Acid (50% aq.) q.s.Dimethicone Copolyol (Aq. Soluble)Preservative5. Shower GelFormula 5 demonstrates the use of cyclomethicone and a high-molecular-weight PDMS (dimethiconol) polymer gum to provide a perceptible after-feelwhen the surfactants are washed off the skin.Formula 5 Shower Gel (47) 29.35% 30.0Water 4.0Sodium Lauiyl Sulfate (30% active) 6.65Cocamide MIPA 6.0Cocamidopropyl Betaine 20.0TEA-Cocohydrolyzed Animal ProteinAcrylates/ClO-30 Alkyl Acrylates Crosspolymer 2.0 2.0 (2%) q.s.Cyclomethicone (and) DimethiconolGlycol DistearatePreservative6. Another Shower GelFormula 6 is another example of the use of a polyether functional siloxane(copolymer of alkyl and polyether functionality) in a personal wash system. Again,the functional siloxane is left on the skin after the surfactant is washed off.Formula 6 Shower Gel (48) 54.5% 2.0Water 2.0Cocoamide MIPA 30.0Laurylmethicone CopolyolSodium Lauryl Sulfate (30%)

Organo-Modlfied Siloxane Polymers 185Decyl Glucoside 6.0Cocamidopropyl Hydroxy-sultaine 3.0PEG-7 Glyceryl Cocoate (and) Polyol Alkyoxy Ester 2.5Preservative q.s.7. Sunscreen LotionFormula 7 is an example of the use of a silicone emulsifier to provide sunscreenactives to the skin from the cyclomethicone continuous phase for improveduniform application. The alkyl methyl siloxane wax (Stearyl Dimethicone) isused to enhance the SPF (Sun Protection Factor) (49).Formula 7 Sunscreen Lotion 6.0%Cyclomethicone 5.0Stearyl Dimethicone 9.5Cyclomethicone (and) Dimethicone Copolyol 4.0Octyl Dimethyl PABA 0.5Laureth-7 74.5Water 0.5Sodium Chloride q.s.Fragrance8. Low-Residue Solid Antiperspirant Though underarm products are designed to reduce odor and wetness, thereis a need to add ingredients that provide a mildness and esthetic that can beconstrued as conditioning. Cyclomethicone, dimethicone, and phenyltrimethi-cone have played critical roles in enhancing the esthetics and uniform deliveryof antiperspirant active salts. Cyclomethicone acts as a transient, non-oilycarrier of actives; dimethicone provides good lubrication and skin feel; andphenyltrimethicone reduces whitening and residue of antiperspirant salts. Formula 8 demonstrates how a high-refractive-index phenyl functionalsiloxane (R.I. = 1.46) can enhance the appearance of an underarm antiper-spirant, minimizing the whitening effect when the cyclomethicone (tran-sient, nonstinging carrier fluid for antiperspirant actives) evaporates.Formula 8 Low-Residue Solid Antiperspirant 42.0% 10.0Cyclomethicone 20.0Phenyl TrimethiconeStearyl Alcohol

186 AbrutynHydrogenated Castor Oil (M.P. 80°C) 4.0PEG-6 Distearate 4.0Aluminum-Zirconium Tetrachlorhydrex-GLY powder 20.0B. Skin Conditioner TrendsCurrent trends continue to move toward non-oily, non-greasy, light-feelingproducts, all of which silicones enhance. A number of patents have been issuedover the past few years that highlight the benefits outlined above for the useof silicones in skin care applications: 1. U.S. Patent 5,013,763 (Tubesing et al), issued in 1991, discusses the use of substantive silicones and quartemium ammonium compounds to leave the skin feeling moist, soft, and smooth even after it has been washed with soap and water. 2. U.S. Patents 5,021,405 and 5,210,102 (Klemish), issued in 1991, discusses the use of amido-functional organo-siloxane mixtures to make skin care products longer lasting and more esthetically acceptable. 3. W.O. 9,209,263 (Alban et al.), published in 1992, discusses the use of polyalkyl, polyaryl, polyalkylaryl, and/or polyether siloxanes in cosmetic gels to control sebum distribution on facial skin and provide improved skin feel, moisturization, rub-in, and absorption characteristics. 4. W.O. 9,307,856 (Decker et al.), published in 1993, discusses the use of alkyl-functional, alkyl/aryl, and/or polyether-functional siloxanes to im- prove skin feel and residue characteristics together with moisturizing, emoUiency, rub-in, and absorption characteristics. 5. U.S. Patent 5,326,557 (Glover et al.), issued in 1994, discusses the use of water-soluble polyether functional siloxanes to aid in humectancy for facial cleansers, moisturizers, and aqueous conditioning gels. 6. W.O. 9,417,774, issued to Procter & Gamble in 1995, discusses the use of silicone gums with a molecular weight of 200,000-400,000 in oil-in- water dispersion to provide improved skin feel and reduced greasiness. 7. W.O. 9,614,054 (Simmons et al.), published in 1996, discusses the use of water-insoluble silicone emollients as emulsions of average particle size 5-4000 Atm to give clear, surfactant-free, low-tack, excellent skin feel, and low irritating hydrogel thickened conditioning composition.III. ORGANO-FUNCTIONAL SILOXANES FOR HAIR CONDITIONINGFunctional siloxanes are used in conditioners, shampoos, mousses, hairsprays,hair colorings, permanent wave applications, and setting lotions. Generally,

Organo-Modifled Siloxane Polymers 187functional siloxanes help condition the hair to improve wet and dry combing,help retain moisture, heighten luster and sheen, improve manageability, andprovide an elegant tactile feel. The term conditioner, in relation to hair groom-ing preparations, refers to ingredients that aid in enhancing manageability,appearance, and feel of hair. Such ingredients should be capable of acting asa lubricant—reducing combing resistance of wet and dry hair, minimizing tan-gling, making hair softer and smoother, and improving set retention whenstyled. These ingredients should also act as antistatic agents to reduce or elimi-nate flyaway hair (especially from dried-out hair) without producing buildupupon repeated application, as this would cause hair to become lank and dull. Organo-modified siloxane polymers demonstrate functionality as effectiveingredients for conditioning hair at low use levels (as low as 1% in mostconditioners and shampoos) (50). Furthermore, blended combinations ofan organo-modified siloxane and an organic conditioner has proven effectivefor conditioning hair. In particular, organo-modified siloxane polymers helpdamaged hair to appear and feel healthier—^without greasy buildup. Besidesreducing combing force, functional siloxanes—particularly the amine-func-tional varieties—can play a unique role in helping to prevent heat damage tohair, Incorporated in cream rinses, they speed drying time by capillary dis-placement of water held between hair fibers. The low surface energies of functional siloxanes allow them to deposit onthe hair surface and spread uniformly as a thin coating on the hair shaft. As aresult of spreading characteristics of functional siloxanes, these organo-silox-ane films have improved durability of the resultant hair coating, are self-heal-ing, uniform, and assist other formulation ingredients to spread on the hairshaft. Durability is proportional to molecular weight or type of functionalgroup attached to the siloxy group. This translates to reduction in combingforces of the hair shaft, leaving a soft, manageable feel to hair. Conditioners that reduce combing force can have a significant impact oncontrolling damage from mechanical stress on hair. Tangle-free combing isimportant to both wet and dry hair, since hair is weakest when saturated withwater. Also, shampoos with conditioning agents that remain on the hair helpcounteract sebum stripping.A. Application ExampiesSilicone technology has advanced dramatically over the past decade, but thebasic (poly)dimethylsiloxane molecule still meets most requirements in con-ditioning the hair for a healthier-looking appearance. As a result, hair careformulators, with a selection of new materials with which to develop highlydifferentiated hair care products, find themselves asking, \"How does one choosethe right functionality of siloxane to achieve desired performance results?\" A

188 Abrutynselection guide (51), as a rational approach to selecting the right functionalsiloxane, has been published to assist the formulating chemist in matching theright functional siloxane to the intended performance benefit required. Depending on how a formulator desires a product to perform, he or she mightchoose a (poly)dimethylsiloxane fluid, polyether-functional siloxane, an amino-functional siloxane, a functional siloxane emulsion, or a clear formulation.1. (Poly)climethylslloxane Fluids(Poly)dimethylcyclosiloxane fluids offer temporary (transient) conditioning,improved wet combing, decreased drying time, resin plasticization, hairfunctional actives carrier, and detangling. Also, as (poly)dimethylcyclo-siloxane fluids evaporate, there remains no residual deposit on hair. Thesecyclical fluids have applications in conditioner (52), 2-in-l shampoo, andstyling products. Linear (poly)dimethylsiloxane fluids and emulsions are typically associatedwith improved conditioning (wet/dry combing) benefits with a nice sensoryfeel—the higher the molecular weight of PDMS fluid, the more effective(lower use levels) are the conditioning effects. Additional benefits for this classof functional siloxanes are reduce flyaway, improved shine, softness, and hu-midity resistance. These linear fluids have application in 2-in-1 shampoos, con-ditioners, styling, and cuticle coat treatment products (53). (Poly)dimethylsiloxanes—^both cyclical and linear—are used to aid in con-ditioning of shampoo bases. Patents have been issued that discuss how to in-corporate water-insoluble siloxane into a surfactant system, while other patentsfocus on the conditioning effects and deposition-aid ingredients. Highermolecular-weight (poly)dimethylsiloxane fluids improve the potential for in-creased conditioning and could require less for equal conditioning effects. a. Pearlescent Conditioning Shampoo. Formula 9 demonstrates the use ofdimethicone (350 cS) to aid wet and dry combing performance. Hydroxyl-propyl methylcellulose is used to disperse and stabilize dimethicone with re-spect to settling.Formula 9 Pearlescent Conditioning ShampooAmmonium Lauryl Sulfate (30%) 30.0%Water 61.0Hydroxylpropyl Methylcellulose 2.0Coconut Diethanolamide 3.0Dimethicone, 350 cS 4.0 q.s. to pH 6.0Citric Acid q.s,Ammonium Chloride

Organo-Modlfied Slloxane Polymers 189 b. High-Shine Cuticle Coat. Formula 10 is an example of the use of highmolecular-weight (poly)dimethylsiloxane polymer gum (dimethiconol) to helpdamaged cuticle. Phenyl Trimethicone is also used to help shine or sheen.Formula 10 High-Shine Cuticle Coat (54) 90.0% 8.0Cyclomethicone (and) Dimethiconol 2.0Q'clomethiconePhenyl Trimethicone2. Polyether Functional SlloxanesPolyether functional siloxanes are typically associated with profoaming, lightconditioning, improved feel (softness), resin plasticization, and anti-irritancy.These polyether fluids have applications in shampoo, conditioner, styling, andmousse products. Polyether functional siloxane fluids provide light to medium conditioning,especially when clarity is required in a formulation. Polyether functional silox-anes can be incorporated into shampoos to give conditioning benefits, aid infoaming efficiency, and reduce the potential for eye irritation caused by an-ionic surfactants used in shampoos. In Figure 11 (55), 3% sodium lauryl sulfate(SLS) + dimethicone copolyol (solid line) is compared to 3% SLS (brokenline) to show the irritation reduction associated with Dimethicone Copolyol. a. Detangling Conditioner. Formula 11 uses a Dimethicone Copolyolto provide water-soluble, mild conditioning. Amodimethicone (as a silicone-in-water emulsion for ease of incorporation) is also used to aid synergisticallyin dry combing.Formula 11 Detangling Conditioner 81.0% 11.0Water 1.5Glycerin 2.0Polysorbate 20 1.0Quatemium-7 0.2Lanolin (and) Hydrolyzed Animal Protein 0.2Panthanol 1.0Imidazolidinyl Urea 2.0Dimethicone CopolyolAmodimethicone (and) Cetrimonium Chloride 0.1 (and) Trideceth-12Methyl Paraben

190 AbrutynFigure 11 Draize mean eye irritation scores. b. Superhold Hair Spray. Formula 12 demonstrates the resin plasticiza-tion properties of Dimethicone Copolyol, aiding in modification of the spraypattern and improved resin performance.Formula 12 Superhold Hair Spray 0.5% 10.0Dimethicone Copolyol 0.2PVM/MA Copolymer, Ethylester 89.3Aminomethyl PropanolSD Ethanol 403. Amino-Functional SiloxanesAmino-functional siloxanes are typically associated with all types of condition-ers and some 2-in-l shampoo products, to improve wet/dry combing, softness,durability, and set retention. Amino-functional siloxane fluids and emulsions provide robust condition-ing to hair because of their substantivity (56). Polar amine groups have a pro-found effect on siloxane deposition properties, giving affinity to the protei-naceous surface of hair. This translates to strong affinity to a hair's surface;and, depending on a formulation, can stay on hair through multiple washings.What is remarkable is that after several treatments, amino-functional siloxanefluids do not build up. In addition to the above, they are easily incorporatedinto clear and opaque hair products. Using 2.5% of an amino-functional silox-ane emulsion and 0.9% of a polyether-functional siloxane in a rinse-out con-ditioner can help combat the effect of sebum stripping caused by excessiveshampooing. By reducing friction and detangling, amino-functional siloxaneat 1% can help prevent damage to hair from combing, without buildup on thehair shaft.

Organo-Modlfied Siloxane Polymers 191 Functional SiloxanesFigure 12 Wet combing data for functional siloxanes in shampoo base. In Figure 12, a graph depicts wet combing data collected from shampoobases in which there are different functional siloxanes at equivalent weightpercent. The data show significant decrease in force during wet combing whenamino-functional siloxanes are used. Therefore, one can provide a premiumconditioner without buildup or affect on curl retention by using a very smallamount of an amino-functional siloxane. a. Durable Conditioning Cream Rinse. Formula 13 illustrates the use ofan amino-functional siloxane (incorporated as a pre-made emulsion for easeof use) to improve wet and dry combing for perceivably better conditioning.Formula 13 Durable Conditioning Cream Rinse 86.5% 0.5Water 2.0Sodium Chloride 5.0Hydroxypropylmethyl Cellulose 1.0Stearalkonium Chloride 5.0Cetyl AlcoholAmodimethicone (and) Cetrimonium Chloride (and) Trideceth-12

192 Abrutyn b. Intensive Conditioner. Formula 14 is an example of another formulaincorporating a ready-to-use amino-functional siloxane emulsion to improvewet and dry comb, and provide soft, silky, and glossy esthetics to hair.Formula 14 Intensive Conditioner 1.5% 91.5Hydroxyethyl Cellulose 2.0Water 5.0Cetyl AlcoholAmodimethicone (and) Cetrimonium Chloride (and) Trideceth-124. Functional Siloxane EmulsionsBoth linear PDMS fluids and amino-functional siloxane fluids (57) can besupplied as silicone-in-water emulsions. As micro- and macroemulsions, linearPDMS fluids and amino-functional siloxanes are easier to incorporate inaqueous surfactant hair preparations. These emulsions can have anionic, cat-ionic, or nonionic charges, which allows incorporation into most aqueous hairpreparations—^without incompatibility problems. a. Conditioning ShampooFormula 15 Conditioning Shampoo 33.0% 3.0Ammonium Lauryl Sulfate (30%) 57.0Cocoamide DEA 6,0WaterDimethicone (and) Laureth-3 (and) 1.0 q.s. to pH 6.0 Laureth-23 Emulsion (50% active of 60,000-cS Dimethicone) q.s.Ammonium Chloride q.s.Citric AcidFragrancePreservativeb. Leave-in ConditionerFormula 16 Leave-in Conditioner 1.8% 1.8Trimethylsilylamodimethicone (and) Octoxynol-40 (and) Isolaureth-6 (and) Glycol EmulsionDimethicone Copolyol

Organo-Modifled Slloxane Polymers 193Water 96.2Quaternium-15 0.2Color/Fragrance/Preservative q.s.c. Rinse-out Conditioner for Damaged HairFormula 17 Rinse-out Conditioner for Damaged HairCeteaiyl Alcohol (and) Ceteth-20 5.0%Sodium Lauryl Sulfate 0.1Perfume 0.4Trimethylsilylamodimethicone (and) Octoxynol-40 6.8 (and) Isolaureth-6 (and) Glycol Emulsion 87.5D.I. Water 0.2Quaternium-155. Clear FormulationsSince some hair preparations require clarity of formulation, silicones must besufficiently compatible with other formula ingredients to maintain clarity offormulation while providing conditioning. Following are some functionalsiloxanes that can be used in clear hair preparations. Microemulsions of linear PDMS fluids can be clear and maintain clarity in hair preparations. Particle size of a linear PDMS droplet is typically less than 50 nm, which results in an optically clear system. Microemulsions are typically used at less than 5% in formulas, representing less than 2.5% of active PDMS. (Poly)diorganosiloxane microemulsions can provide enhanced dilution and formulation stability for easier delivery of func- tional benefits. Polyether functional siloxanes are water soluble when there is a sufficient level of polyoxyethylene attached to the siloxane backbone (typically as- sociated with high calculated HLB). Also, they can reduce the viscosity of aqueous-based surfactant formulas; thus, when they are used in these formulas, addition of salt or a viscosity booster is recommended. Poly- ether functional siloxanes are typically used in formulas at 5% to provide light conditioning of hair. a. Clear Conditioning Shampoo. Formula 18 illustrates the use of a high-calculated-HLB surfactant (12-14), which is soluble in the surfactant system,providing mild conditioning. These polyether functional siloxanes typicallyhave an inverse cloud point (losing solubility as temperature rises). They cloud

194 Abrutynout of shampoo formula around normal hot bath water temperature (cloudpoints ranging from 40 to SS^C) and deposit on the hair—not easily rinsed offwith a shampoo surfactant system.Formula 18 Clear Conditioning Shampoo 2.0% 30,0Dimethiconol Copolyol 2.0Sodium Lauryl Ether Sulfate (30%) 1.5Cocoamide DBA q.s. to 100%PEG-120 Methyl Glucose Dioleate q.s.Water q.s.Citric Acid q.s.Sodium ChlorideFragrance/Preservative Amino-functional siloxanes can be incorporated directly or via micro- ormacroemulsion into clear shampoos and aid in strong conditioning and fasterdrying of hair. Amino-functional siloxanes also have been noted to reduceviscosity of a formulation; thus, when they are used in a surfactant-based for-mula, addition of salt or a viscosity booster is recommended. They are typicallyused in hair preparations at less than 1%. Work reported by Jachowicz andBerthiaume (58) suggests the ability of amino-functional siloxane microemul-sions to penetrate into the interior of a hair fiber. b. Conditioning Setting Gel. Formula 19 incorporates a cyclomethicone/dimethicone copolyol to aid in drying time and mild conditioning of hair. Tri-methylsiloxyamodimethicone is used to give a durable dry-combing condition-ing effect, even after a few shampoo washings, and to provide softness and anoticeably reduced drying time.Formula 19 Conditioning Setting Gel 10.0%Vinylcaprolactam PVP/ 0.5 Dimethylaminoethylmethacrylate Copolymer 0.5Trimethylsilyamodimethicone (and) Octoxynol-40 1.0 (and) Isolaureth-6 (and) Glycol Emulsion 1.4 86.6Cyclomethicone (and) Dimethicone Copolyol q.s.Carbomer 940Sodium Hydroxide (20%)D.I. WaterPreservative/Color/Fragrance

Organo-Modifled Siloxane Polymers 195B. Hair Conditioner TrendsSeveral authors have studied the fundamentals of hair conditioning using sili-cones, so that the phenomenon is reasonably well understood (59). Materialsand delivery-system innovations have continued, as evidenced by a number ofpatents which have been issued over the past few years that highlight the bene-fits outlined above from the use of silicones in hair conditioning applications.Selected references are noted in the areas of silicone microemulsions, T/Q-type organosilicon compounds, further derivatization of organo-functionalsiloxanes, enhanced performance/delivery, and new formulations: 1. G.B. 9,117,740 (Birtwistle) discusses the use of microemulsions of func- tional siloxanes (particle size less than 1 m) and cationic deposition polymers in various types of surfactant systems to be compatible in 2-in-l optically clear shampoos to impart good conditioning benefits to hair and skin. 2. E.P, 0,268,982 (Harashima et al.) discusses the use of dimethylsiloxane microemulsions in cosmetic formulations. 3. U.S. 5,661,215 (Gee et al.) discusses gel-free crosslinked polydimethyl- siloxane polymer microemulsions for hair conditioning applications that require lubrication properties without excess tackiness. 4. U.S. 5,244,598 (Merrifield et al.) discusses the preparation of amino- silicone microemulsions for hair conditioning. 5. U.S. 5,085,859 (Halloran et al.) discusses the use of T-type organosili- con compounds for curl retention of hair. 6. U.S. 5,135,742 (Halloran et al.) discusses the use of organo-modified T-type organosilicon compounds for imparting curl retention to hair. 7. J 94,282,138 (assigned to Shiseido Co., Ltd.) discusses the use of organic silicone resins that have good setting power and gives good glossiness and smoothness to hair. 8. GB 2,229,775 (Berthiaume et al.) discusses the use of low-viscosity or- gano-functional siloxysilicate resins to improve shine, volume, body, and curl retention in hair, and reduced combing force. 9. U.S. 5,226,923 (O'Lenick) discusses the use of silicone fatty acid esters to provide softening and lubrication when applied to hair and skin. They also afford antistatic properties. 10. E.P. 0,723,770 (Cretois et al.) discusses the use of modified oxyalkylene- substituted silicones in a guar gum surfactant system that oversomes undesirable residue left on hair and poor fixing power. 11. U.S. 5,409,695 (Abrutyn et al.) discusses the use of a polymeric lattice network to deliver functional siloxanes to the hair in a controlled manner.

196 Abrutyn 12. D.E. 4,324,358 (Hilliard et al.) discusses the use of (poly)dimethylsilox- ane (1,000-120,000 cS viscosity) in bar soaps at 1-6% to provide softer, glossier hair and skin.IV. CONCLUSIONSFormulators have come to trust the safety of silicones—a wide range of studiesdocument a low order of toxicity (60). For this reason, the (poly)dimethylsilox-ane backbone has become a key conditioning ingredient for both skin care andhair care applications. It was not too long ago that silicones were a strange andunique cosmetic additive, but today more than 50% of all new cosmetic andtoiletry products have at least one silicone incorporated to aid in esthetics,improve delivery, or improve application ease to the skin and hair, or to pro-vide a functionalized performance (e.g., nonwhitening/nonresidue, emulsifi-cation, enhanced substantivity, enhanced sun protection). Polyether functionalsiloxanes and amino-functional siloxanes will continue to play an importantrole in conditioning of hair, but branching and crosslinking of the basic (poly)di-methylsiloxane molecule will emerge as an important classification to improveddeposition and measurable performance. Alkyl methyl siloxanes and copoly-mers will emerge as important classifications for improved deposition on skin.Polyether functional siloxanes (and copolymers) will continue their growth asimportant water-in-oil/silicone emulsifiers. There is still a need to understand further how to deposit functional silox-anes more efficiently to hair and skin and then demonstrate the durability ofthe resultant silicone film. Learning more about the effect of other formula-tion ingredients will assist in understanding deposition effectiveness.REFERENCES 1. Fearon FWG. In: Seymour R, Kirsenbaum G, High Polymers. Elsevier, 1986. 2. Rochow EG. Silicon and Silicones. Springer-Verlag, 1987. 3. Colas A. Silicone chemistry overview. Chemie Nouvelle 1990; 8(30):847. 4. Schorsch G. Silicones: Production and Applications. Techno-Nathan Publishing, 1988. 5. Rochow EG. Silicon and Silicones. Springer-Verlag, 1987. 6. Hardman B. Silicones. Encyclopedia of Polymer Science & Engineering. Vol. 15. 1989:204. 7. Sauer RO. Nomenclature of organosilicon compounds. J Chem Educ 1944; 21: 303. 8. American Chemical Society Nomenclature, Spelling and Pronunciation Commit- tee. Chem Eng News 1952; 30:4517. 9. Editorial report on nomenclature. J Chem Soc 1952:5064.10. lUPAC, CR 15th Conference 1949:127-132; Information Bulletin No. 31, 1973:87.

Organo-Modified Slloxane Polymers 1971 la. Wendel SR. Use of silicones in cosmetics and toiletries. Perfums, Cosmetic Aromes 1984:59,67.lib. Disapio AJ. Silicones in personal care: An ingredient revolution. Drug Cosmet Ind 1994 (May).12. Stark FO. Silicones. In: Comprehensive Organometallic Chemistry. Vol. 2. Per- gamon Press, 1982:305.13. Stark FO, et coll. Silicones. In: Encyclopedia of Polymer Science & Engineering. Vol. 15.1989:204,14. Allred L, Rochow EG, Stone FGA. The nature of the silicon-oxygen bond. J Inorg Nuclear Chem 1956; 2:416.15. Corey NY. Historical overview and comparison of silicon with carbon. In: Patai S, Rappoport Z, eds. The Chemistry of Organic Silicon Compounds. Wiley, 1989: chap 1.16. Disapio AJ. Silicones in personal care: an ingredient revolution. Drug Cosmet Ind 1994 (May).17a. Noll W. Chemistry and Technology of Silicones. New York: Academic Press, 1968.17b. Dean JA, ed. Lange's Handbook of Chemistry, 13th ed. New York: McGraw-Hill, 1985.18. Ferry J. Visco-Elastic Properties of Polymer. 3d ed. New York: Wiley, 1980.19a. Carter W. Pierce J, Malkina I, Luo D. Investigation of the ozone formation po- tential of selected volatile silicone compounds. Final report from Statewide Air Pollution Research Center, University of California, Riverside, CA, to Dow Corning Corporation, Oct. 1992.19b. 59 Fed Reg 192, Oct, 5,1994, pp. 50693-50696.20a. Urrutia A, Glover DA, Oldinski RL, Rizwan BM. Sensory evaluation of silicones for personal care applications. XIII Congreso Latino-Americano e Ib'erico de Quimicos Cosme'ticos, Acapulco, Mexico, Sept. 21-26,1997.20b. IFSCC Monograph No. 1.21a. 21CFR Part 347,25204-25232 (Vol. 55, No. 119), June 29,1990. Proposed \"Skin Protectant Drug Products for Over-the-Counter Human Use.\"21b. 21 CFR Part 347, Docket No. 78N-0021 (48 Fed Reg 6820), Feb, 15,1983. Notice of Proposed rulemaking \"Skin Protectant Drug Products for Over-the-Counter Human Use; Tentative Final Monograph.\"22. Natl Formulary 18, pp. 2242-2243 (1995).23. 59 Fed Reg No. 192, Oct. 5,1994, pp. 50693-50696.24. Disapio AJ, Fridd P. Silicone glycols for cosmetic and toiletry applications, IFSCC, London, Oct. 1988.25. Tradename registered to Dow Corning.26a. Kasprzak KA. Emulsion techniques using silicone formulation aids. Drug Cosmet 1996 (May).26b. Gruening S, Hemeyer P, Weitemeyer C. New types of emulsions containing or- gano-modified silicone copolymers as emulsifiers. Tenside Surfactants Deterg 1992; 29(2):78-83.27. Zombeck A, Dahms G. Novel formulations based on nonaqueous emulsions of polyols in silicones. 19th IFSCC Congress, Sydney, October 22-25,1996.

198 Abrutyn28. Dow Corning Corporation. Shower: Formulation Guide. Dow Corning, Midland, MI.29a. Handt CM. Hair fixative benefits from the physical and chemical properties of silicones. Soap Cosmet Chem Spec 1987,29b. Personal communications from National Starch.30a. Cosmetic Ingredient Review. Final report on the safety assessment of dimethi- cone copolyol. J Am Coll Toxicol 1991; 10(1).30b. Dow Corning Corporation. Internal report.31. Smith JM, Madore LM, Fuson SM. Attacking residue in antiperspirant—alter- native to the clear stick. Drug Cosmet 1995; (Dec,):46-52.32. Disapio AJ, LeGrow GE, Oldinski RL Correlation of physical and sensory prop- erties of alkylmethylsiloxanes with their composition and structure. IFSCC, Ja- pan, 1994.33. Van Ree± I, Wilson A. Understanding of factors influencing the permeability of silicones and their derivatives. Cosmet Toilet 1994 (July).34. Glover DA. Unique alkyl methyl siloxane waxes for personal care. Cosmet Toilet. In press.35. Starch MS, Silicones in hair care products. Drug Cosmet Ind 1984 (June):38-44.36. Starch MS. Silicones for conditioning of damaged hair. Soap Cosmet Chem Spec 1986 (Apr.).37. Schulz WJ, Zhang S. Silicone Oils and Solvents Thickened by Silicone Elastomers. U.S. Patent 5,654,362,1997.38. U.S. Patent 4,987,169, U.S. Patent 5,412,004, and U.S. Patent 5,236,986.39. Stepniewski GJ, et al. Stable Water-in-Oil Emulsion Systems. U.S. Patent 5,599,533, 1997.40a. Halloran DJ, et al. Hair Treatment for Curl Retention—Using Fixative Resin Film-Forming Non-Polar Silsesquioxane. U.S. Patent 5075103,1992.40b. Halloran DJ, et al. Imparting Curl Retention to Hair—By Using Pre-Hydrolyzed Organo-Functional Silane with Silsesquioxane Properties as Film Former. U.S. Patent 5,135,742,1992.41. Woodruff J. Manufact Chem 1996; 67(6);27-31. Defining the term emollient and key physical and perception characteristics.42. Blakely JM. The benefits of silicones in facial and body cleansing products. IFSCC, Japan, 1994.43. Dow Corning Corporation (Midland, MI) Formulation #E6845-128B.44. Dow Corning Corporation (Midland, MI) Formulation #23/887.45. Dow Corning Corporation (Midland, MI) Formulation #7/691.46. Dow Corning Corporation (Midland, MI) Formulation #25-334-92.47. Dow Corning Corporation (Midland, MI) Formulation #140/7.48. Dow Coming Corporation (Midland, MI) Formulation #12/194.49. Van Reeth IM, Dahman F, Hannington J. Alkyl methyl siloxanes as SPF en- hancers: relationship between effects and physio-chemical properties. IFSCC, Sydney, Oct. 1996.50. DeSmedt A, Van Reeth IM, Machiorette S, Glover DA, Nard J. Measurements of silicone deposition on hair by various analytical methods, Cosmet Toilet 1997 (Feb.); 112(2).

Organo-Modified Siloxane Polymers51. Halloran DJ. A silicone selection guide for developing conditioning shampoos. Soap Cosmet Chem Spec 1992 (Mar.):22-26.52. Wagman J, et al. Aqueous Hair Conditioning Compositions. U.S. Patent 4,777,037.53a. Geen H. Nontangling Shampoo. U.S. Patent 2,826,551.53b. Pader M. Freely-Pourable, Stable, Homogenous, Shampoo Composition. U.S. Patent 4,364,837.54c. Fieler et al. Process for Making a Silicone Containing Shampoo. U.S. Patent 4,728,457.53d. Bolich R, et al. Hair Care Composition Containing a Rigid Silicone Polymer. U.S. Patent 4,902,499.53e. Conditioning Shampoo Comprising a Surfactant, Non-volatile Silicone Oil, Guar, Hydroxypropyl Trimonium Chloride, Cationic Conditioning Polymer. U.S. Pat- ent 5,151,210.54. Thomson B, Vincent J, Halloran D. Anhydrous hair conditioners: silicone-in-sili- cone delivery systems. Soap Cosmet Chem Spec 1992 (Oct.); 68(10):25-28.55. Disapio A, Fridd P. Silicones: use of substantive properties on skin and hair. Int J Cosmet Sci 1988; 10:75-89.56a. Halloran D. Silicones in shampoos. HAPPI1992 (Nov.):60-64.56b. Sejpka J. Silicones in hair care products. Seifen, Oele, Fette, Wachse 1992; 118 (17):1065-1070.56c. Demarco et al. Aqueous Hair Conditioning Compositions. U.S. Patent 4,529,586.56d. Halloran D, et al. Clear Shampoo Compositions. U.S. Patent 5,326,483.56e. Madrange et al. Detergent Cosmetic Composition. U.S. Patent 4,710,314.56f. Starch MS. Hair Conditioners Containing Siloxane and Freeze-Thaw Stabilizers. U.S. Patent 4,563,347.56g. Optically Clear Hair Care Compositions Containing Silicone Microemulsions. E.P. 514,934 Al.56h. Chandra et al. Conditioning Shampoos Containing Amine-Functional Polydior- ganosiloxanes. U.S. Patent 4,559,227.56i. Krzysik D, Gatto S. Black hair care products: new formulating concepts with silicones. Drug Cosmet Ind 1987 (Nov.).56j. Traver F, et al. Dialkylaminoalkyl Siloxy Terminated Polydiorganosiloxane Com- pounds. U.S. Patent 5,132,443.57. Gee. A Method of Preparing Polyorganosiloxanes Having Small Particle Size. U.S. Patent 4,620,878.58. Jachowicz J, Berthiaume M. Microemulsions vs. macroemulsions in hair care products. Cosmet Toilet 1993; 108:65-72.59a. Nanavati S, Hami A. A preliminary investigation of the interaction of a quater- nium with silicones and its conditioning benefits on hair. J Soc Cosmet Chem 1994 (May-June); 45:135-148.59b, Robbins CR, Reich C, Patel A. Adsorption to keratin surfaces: a continuum be- tween a charge-driven and a hydrophobically driven process. J Soc Cosmet Chem 1994 (Mar.-Apr.); 45:84-94.59c. Lockhead RY. Conditioning shampoos. Soap Cosmet Chem Spec 1992 (Oct.): 42-49.

200 Abrutyn59d, Jachowicz J, Berthiaume M. Heterocoaggulation of silicone emulsions on keratin fibers. J Colloid Interface Sci. 1989; 133:118-134.60a. Chandra G, Disapio A, Frye C, Zellner D. Silicones for cosmetic and toiletries: an environmental update. 1994.60b. Crowston E, Kolaitis L, Verbiedse N. Purity as a unique quality property of Dow Corning dimethicone and cyclomethicone product line in the cosmetic industry. 1996.60c. Disapio AJ, Zellner AN. Silicones (polydimethylsiloxanes): a profile for safety and functional performance in cosmetics and toiletries. 1994.60d. Verbiese N. Organosihcon compounds as cosmetic ingredients and European regulatory environmental trends. 1994.

9Specialty Silicone Conditioning AgentsAnthony J. O'Lenick, Jr.Lambent Technologies, Norcross, GeorgiaI. INTRODUCTIONSilicone compounds have enjoyed growing acceptance in a variety of personalcare applications. This is true in part due to advances in the formulation tech-niques used in the preparation of silicone-containing products. Equally impor-tant and potentially more exciting to the formulator, however, is the synthesisand commercial availability of a variety of new organof unctional silicone com-pounds which offer both ease of formulation and enhanced performance informulations.II. BACKGROUNDA. Historic Uses of PolyslloxanesSilicone compounds have been known since 1860, but were of little commer-cial interest until the 1940s. Over the years, silicone compounds have receivedgrowing acceptance in many personal care applications. In fact, it has beensaid that four of ten new personal care products introduced in the 1990s havesilicone in them. There has been considerable confusion related to nomencla-ture of silicone compounds. The term silicon (no \"e\") refers to the elementsilicon (atomic number 14) and is correctly used to describe simple, nonpo-lymeric compounds such as SiS2 (silicon disulfide). The term \"silicone\" wascoined by F. S. Kipping to designate an organosilicon oxide polymer. The firstof these compounds were thought to be silicon-based ketones, hence the con-traction silicone. Despite this error, the term is still widely used and accepted. 201

202 O'LenickThe vast majority of the volume of silicone compounds used are silicone fluids,also known as polysiloxanes. They are the oldest and perhaps the best under-stood of the silicone compounds in use today. There has been a recent explo-sion in the availability of chemically modified silicone compounds that provide(a) conditioning, (b) softening, (c) irritation mitigation, (d) barrier properties,and (e) emulsification. This is due to the fact that many of the desirable prop-erties that f ormulators want in their products cannot be achieved using siliconefluids alone, hydrocarbons alone, or blends. Blends are ineffective becausesilicone fluids and hydrocarbons are insoluble in each other. Organosiliconcompounds offer the possibility of combining the best properties of each typeof compound in one hybrid molecule. The hybrid molecule that results can betailored for its properties in specific formulations. Silicone fluids, also called silicone oils, are sold by their viscosity and rangefrom 0,65 cs to 1,000,000 cs. These materials are discussed at length in Chapter8. Unless the silicone fluid is made by blending two different-viscosity siliconefluids, the molecular weight of the silicone fluid is dependent on the numberof repeating units in the polymer. Perhaps the major recent development inthe use of silicone fluids in personal care is the so-called two-in-one shampoo.This technology was pioneered by Procter and Gamble and is the topic of manyof their patents (1-6). The basic concept in these systems is to disperse siliconefluids in a thickened shampoo base and deliver the silicone fluid to the hairduring the shampoo process, providing both cleaning and conditioning. Thesilicone is delivered to hair or skin this way due to a hydrophobic interaction.When oil is placed into water, it disrupts the hydrogen bonding between thewater molecules in the water solution. This disruption is accomplished onlywhen the energy of mixing is sufficient to break the hydrogen bonds. Whenthe mixing is stopped, the oil is forced out of the water by the re-formation ofthe hydrogen bonds between the water molecules. This phenomenon can beused to deliver oil to a surface. Much has been written about the desirabilityof using silicone oil as a replacement for mineral oil in many cosmetic appli-cations (7). The choice of materials should be based solely on the cost effec-tiveness of achieving the desired properties in the formulation; some formu-lations use both mineral oil and silicone fluid.B. Drawbacks of PolysiloxaneDespite the fact that silicone fluids function in many applications, there are anumber of formulations in which silicone fluids cannot be used. Among theirdrawbacks are the following. 1. Silicone fluids defoam many formulations, limiting their utility. 2. Silicone fluids lack solubility in water and in many organics and therefore are very difficult to use in formulations.

Specialty Silicone Conditioning Agents 2033. Silicone fluids are greasy.4. Silicone fluids need to be emulsified to be used in water-based systems.C. Improving Silicone Properties by Modifying OrganofunctionalityThe above-mentioned negative effects can be reduced by modifying thesolubility of the polysiloxane molecule. This can be accomplished by addingvarious organofunctional constituents to the silicone chain. These modifi-cations allow the material to be delivered to the skin or hair in ways otherthan the hydrophobic interaction described above. One way to modify thesolubility of polysiloxane is to insert into the silicone molecule groups thatmodify the solubility of the resultant compound. Such groups include hy-drocarbon groups that effect organic solubility, and polyoxyalkylenegroups that effect water solubility. Silicone compounds that have hydro-carbon groups and/or polyoxyalkylene groups are one class of compoundsreferred to as organofunctional silicone polymers. Silicone modified in thisway may be adhered to the skin or hair by virtue of one or more of thefollowing mechanisms. Ionic interactions. The charge on the molecule will also have an effect on the delivery of the oil to the hair or skin. For example, if the oil has a cationic charge on the molecule, it will form ionic bonds with substrates which contain negative surface charges. The two opposite charges to- gether form a so-called pair bond. General adhesion. If an oil is delivered to the skin or hair penetrates and then polymerizes, an interlocking network of polymer will develop. Al- though it is not bonded directly to the substrate, this polymer network will adhere to the substrate. Specific adhesion. If an oil is delivered to the skin or hair penetrates and then reacts with groups on the hair or skin, there will be a chemical bond between the polymer and the substrate. This is the strongest and most permanent of the adhesion mechanisms. Silicone fluids react almost exclusively by the hydrophobic mechanismdescribed above. To the extent that other mechanisms may be introduced,the more strongly and efficiently the conditioner can be delivered to sub-strate. Organofunctional silicone seek in large part to capitalize on these ad-ditional mechanisms to provide thorough and efficient conditioning for hairand skin.

204 O'LenickIII. TYPES OF ORGANOFUNCTtONALLY MODIFIED SILICONE POLYMERSA. DImethlconol1. Structure/BackgroundAn important class of reactive silicone compounds id dimethiconols. This classof compounds has an Si-OH group and is also known as silanols. Dimethiconolcompounds conform to the following structure:1where Me is methyl.2. Properties/ApplicationsLike dimethicone compounds, dimethiconol compounds are sold by viscosity.Under certain conditions, dimethiconol compounds homopolymerize to givehigher-molecular-weight species. The polymerization can be accomplishedafter the lower-molecular-weight polymer penetrates the hair or skin. Thistype of polymerization can result in an interlocking polymeric compoundthat adheres to the substrate. Dimethiconol can be supplied in emulsionform that can be applied to treated or colored hair to lock in the color ortreatment. The initial mechanism of conditioning the substrate is hydrophobicinteraction, but unlike silicone fluids, these materials can polymerize foradded durability. In addition to their usefulness in emulsions, another property of dimethi-conol compounds is their ability to react to make organofunctional com-pounds. The reactivity of the dimethiconol group toward fatty acids to makeesters has been compared to the reactivity of carbanols in fatty alcohols (8).Dimethiconols were found to be only slightly less reactive than the carbanolswhen esterified. This fact clearly illustrates why dimethiconols can be used ina variety of surfactant unit operations to give silicone surfactants. This reac-tivity of the dimethiconol group allows for the preparation of surfactants, inwhich silicone is a hydrophobe. The properties of the final surfactant dependon the silicone chosen and can be either hydrophobic and lipophobic. This isa result of the insolubility of the silicone in many hydrocarbons and in water.Silanols, or dimethiconols, are made by the polymerization of cyclic siliconecompounds using acid catalysts and water.

Specialty Silicone Conditioning Agents 205B. Dimethicone Copolyol1. Structure/BackgroundAnother major class of silicone derivative is dimethicone copolyol. This mate-rial is used as a conditioning agent as well as to synthesize other derivatives.Dimethicone copolyols have carbanol hydroxyl groups and silicone present.The introduction of fatty groups into the molecule using classical surfactantchemistry can result in a molecule that has a silicone portion, a polyoxyal-kylene portion, and a fatty portion. This leads to a molecule that has a water-soluble part, an oil-soluble part, and a silicone-soluble part. Dimethicone co-polyols conform to the following structure: Dimethicone copolyols are prepared using a process called hydrosilylation.In this process a polymer having a silanic hydrogen present (Si-H) is reacted withan allyl alcohol alkoxylate, for examplein the presence of a suitable catalyst. Commonly the catalyst contains platinum. Several types of organofunctional compounds can be made based on thelocation of the functional group. For example, the comb product conforms tothe structurewhile the terminal product conforms to the structure

206 O'Lenick The term dimethicone copolyol, while descriptive of a class of compounds,does not describe a specific compound. This leads to confusion in the fieldwhen a formulator asks for dimethicone copolyol. The major variables thateffect performance include (a) whether the compound is comb or terminal,(b) the molecular weight of the compound, (c) the ratio of silicone to polyoxy-alkylene, and (d) the amount and location of polyoxyethylene or poly-oxypropylene in the molecule. As a result, it is impossible to determine if acompound described as a dimethicone copolyol is water soluble or insoluble,or if it is to be used as a conditioner or an emulsifier.2. Properties/ApplicationsIn addition to being raw materials for preparation of other silicone surfactants,dimethicone copolyols have been used per se in many formulations. Dimethi-cone copolyol compounds have a wide range of applications in personal careapplications. a. Emubification. One area is as an emulsifier for use in antiperspirants.In this application, the dimethicone copolyol generally is sold in cyclomethi-cone and is referred to as a formulation aid. The product emulsifies aqueousantiperspirants into cyclomethicone. b. Emolllency. If the concentration of polyoxyethylene in a dimethi-cone copolyol is raised in the molecule, a solid waxy material results. Di-methicone copolyol compounds of this type are outstanding water-solubleemollients. c. Conditioning. Because dimethicone copolyol compounds are nonionic,they are compatible with anionic surfactants, and consequently have foundapplication in a variety of shampoos that contain conditioning agents. d. Resin Modification. Dimethicone copolyol compounds are used tomodify resins, for hairspray and mousse. The presence of silicone results in aplasticizer effect on the resin, making it less harsh on the hair.C. Alkyl Dimethicone Copolyol1. Structure/BackgroundRecently a series of compounds that have both alkyl groups and polyoxyal-kylene groups have been promoted in the personal care market (9). Thesecompounds conform to the following structure:

Specialty Silicone Conditioning Agents 207 Alkyl dimethicone copolyols, like their non-alkyl-containing counterparts,are prepared using a process called hydrosilylation. In this process a polymerhaving a silanic hydrogen present (Si-H) is reacted with an allyl alcohol alk-oxylate and an alpha-olefin. For example, a mixture of ^ can be co-hydrosilylated withthe Si-H polymer m the presence of a suitable catalyst. Commonly the catalystcontains platinum.2. Properties/ApplicationsThese materials are used as emulsifiers in the preparation of both water-in-silicone and silicone-in-water systems. These products provide advantagesover traditional hydrocarbon chemistries since they can be used in the prepa-ration of emulsions without heat. These silicone polymers can be used to pre-pare products that contain little wax, contain a large concentration of water,and have a light spreadable feel on the skin.D. Trimethylsllylamodlmethicone1. Structure/BackgroundSilicone compounds containing amino groups are widely used in personal careapplications. They conform to the following structure (10):The CTFA name is trimethylsilylamodimethicone, or TSA, for short. Com-pounds conforming to this structure are affective conditioning agents.

208 O'Lenick2. Properties/ApplicationsSince the amino group has a pKb of about 10.7, use of these materials at pHbelow this value results in the protonation of the amino group. Consequently,these compounds act as cationics at pH below their pKb. The cationic natureof these compounds results in the adhesion to hair and skin using ionic inter-actions. Generally this class of product is used at around 1-3% concentration,and provides intensive conditioning.E. Amodimethicone1. Structure/BackgroundAmodimethicone is a 35% solids emulsion in water and is made by emulsionpolymerization. The resulting emulsion contains water, the amodimethicone,surfactants, and fatty quaternium. The structure is2. Properties/ApplicationsAmodimethicone differs from trimethylsilylamodimethicone in that the for-mer has a reactive silanol group (Si-OH). This group, in the presence of theamino group, will polymerize to form a higher-molecular-weight polymer. Thisproperty together with the amino group, which below a pH of 10.7 is cationic,results in improved durability and substantivity in many formulations. Thesecompounds are outstanding conditioners and have good skin feel. There areemulsions, however, and so are inherently less stable than solutions of thesame product. Therefore, several considerations that must be made in formu-lating with this type of material. These include (a) freeze-thaw stability, (b)shear sensitivity, and (c) HLB incompatibility. These considerations may limitthe amount of material that can be added to a given formulation, or may pre-clude the use of the material in certain formulations at all. Despite the factthat amodimethicone is available only as an emulsion, it has been used suc-cessfully for many years in many different applications both for hair and skincare.

Specialty Silicone Conditioning Agents 209F. Dimethicone Copolyol Amine1. Structure/BackgroundMore recently, a series of polymers related to amodimethicone has come ontothe market (11). These products have the same structure, but in addition havea water-loving polyoxyalkylene glycol group present. Unlike amodimethicone,these products are not made by emulsion polymerization. They do not containadded surfactant or fatty quaternary, as can be seen in the following structure:I2. Properties/ApplicationsThe introduction of the polyoxyalkylene glycol portion into the molecule al-lows for the regulation of water solubility. Products are available that are watersoluble, self-emulsifying, or water insoluble. Conditioning comes from twogroups: (a) those based on the value of n, and (b) the number of amino groupspresent. The a value results in a more greasy conditioning, like silicone fluid.The amino conditioning is a more slick feel. The durability of the polymer toa variety of substrates can be altered by the concentration of silanol (Si-OH)groups. Products run from mildly conditioning, for every day use, to extremelydurable. Since these materials are not emulsions, they are freeze-thaw stable,shear stable, and can be used in formulations having a relatively wide range ofHLB values. The presence of the polyoxyalkylene glycol prevents these mate-rials from being gunky on the hair or skin. They impart a very luxurious feelto the skin.G. Silicone Quaternium Compounds1. Structure/BackgroundFatty quaternary compounds, discussed elsewhere in this book, are well-knownconditioners. There can be several undesirable attributes of fatty cationic prod-ucts which limit their usefulness in certain formulations. For example, fattycationic surfactants are incompatible with anionic surfactants, forming insol-uble complexes when the two types of materials are combined (12). Cationicsare considered somewhat toxic when ingested and they are eye irritants, butthey tend not to be topical irritants (13). Fatty alkylamidopropyl dimethyl-

210 O'Lenickammonium compounds are commonly found in conditioning treatments forhair, but are difficult to formulate in clear shampoo systems (14). Many ofthese limiting attributes can be mitigated by making silicone analogs of fattyamidopropyl dimethylamine quaternary compounds. A series of alkylamidosilicone quaternary compounds based on dimethicone copolyol chemistry hasbeen developed. These materials are compatible with anionic systems, over alimited range of concentrations; provide outstanding wet comb properties,antistatic properties, and nongreasy softening properties to hair, fiber, andskin; and are not based on glycidyl epoxide or alkanolamine chemistries. Com-pounds can be prepared that have varying amounts of polyoxyalkylene oxidein the polymer. The ability to regulate the type of alkylene oxide and theamount present in the silicone polymer results in a series of products rangingin water/oil solubility. Compounds of the comb type conform to the followingstructure: Compounds of this type are prepared in a two-step reaction sequence. Firstthe dimethicone copolyol is esterified with chloroacetic acid. The resultingdimethicone copolyol chloro-ester is then used to quaternize a tertiary aminein aqueous solution. Typically, the tertiary amine is an alkylamidopropyl di-methyl amine.2. Properties/ApplicationsSilicone quatemium compounds of the above type have been designated bythe CTFA as silicone quaternium 1 through silicone quatemium 10. They canbe easily formulated into a variety of personal care products, without emulsi-fication, the use of elaborate thickening systems, or homogenization. Thesehave outstanding compatibility with nonionic and other cationic materials and,more surprisingly, compatibility with anionic surfactants. For example, 3%

Specialty Silicone Conditioning Agents 211Table 1 Silicone Quaternary CompoundsCTFA name Alkyl amide groupSilicone quaternium 1 CocamidopropyldimethylSilicone quaternium 2 MyristamidopropyldimethylSilicone quaternium 8 Di-linoleylamidopropyldimethylsilicone quaternium 8 can be incorporated into 15% sodium lauryl sulfate cold,with only mild agitation. This results in a clear simple base for the formulationof two-in-one shampoos that are nongreasy and do not build up. Wet combingstudies also indicate significant conditioning benefits. Additionally, the sili-cone quaternium gives antistatic properties and gloss, while any attempt toincorporate silicone oil into this type of formula results in a hazy, low-foamingproduct that separates into two phases quite rapidly. The silicone quaterniumcompounds of this class that are available commercially are shown in Table 1. Other noteworthy properties include the effect on foam properties andTheological characteristics. Silicone quaternium 8 was added to a conventionalshampoo formula and evaluated for initial foam height and foam stability.Both factors were improved by the incorporation of the silicone quat. When salt (NaCl) was added to a test formulation consisting of sodiumlauryl sulfate, cocamide DEA, and silicone quaternium 8, the presence ofthe silicone quat lowered the viscosity from a peak viscosity of 15,000 cps toabout 8,000 cps. The percentage added salt to reach peak viscosity was notaltered. To obtain viscosities above those shown using the silicone quat, alter-native thickeners can be used. These include polyacrylates, guar gums, andxanthanes.H. Silicone Surfactants1. Structure/BackgroundFormulators in the personal care field realize that there are a vast number oftraditional surfactants from which to chose in the preparation of new products.Nonionic, cationic, amphoteric, and anionic products are available, and withineach class there are numerous products. A neophyte formulator might ask,\"Why are there so many types of surfactants?\" The answer is clear: the struc-ture of the surfactant determines the functionality. For example, if you areseeking a conditioner for hair, more than likely you would choose a quaternarycompound, not a nonionic. It makes sense, then, that incorporation of func-tional groups into silicone-based surfactants should also have a profound effect

212 O'LenIckTable 2 Comparison of Hydrocarbon and Silicone DerivativesHydrocarbon products Silicone productsAnionics Silicone phosphate esters (10) Phosphate esters Silicone sulfates (11) Sulfates Silicone carboxylates (12) Carboxylates Silicone sulfosuccinates (13) Sulfosuccinates Sihcone alkyl quats (14)Cationics Silicone amido quats (15) Alkyl quats Silicone imidazoline quats (16) Amido quats Imidazoline quats Silicone amphoterics (17) Silicone betaines (18)Amphoterics Silicone phosphobetaines (19) Amino proprionates Betaines Dimethicone copolyol Phosphobetaines Silicone alkanolamids (20) Silicone esters (21)Nonionics Silicone taurine (22) Alcohol alkoxylates Silicone isethionates (23) Alkanolamids Silicone glycosides (24) Esters Taurine derivatives Silicone free-radical quats (25) Isethionates Silicone polyaciylate copolymers (25) Alkyl glycosides Silicone polyaciylamide copolymers (25) Silicone polysulfonic acid copolymers (25)Free-radical polymers PVP/quats Polyacrylates Polyacrylamides Polysulfonic acidson properties. Prior to 1990, dimethicone copolyols were the principal siliconesurfactant available to the formulating chemist. Dimethicone copolyols arenonionic compounds analogous to alcohol ethoxylates. It is not surprising,then, that a series of surfactants based on silicone as a hydrophobe, whichcontain other functional groups similar to those seen in traditional surfactants,would be developed. In some instances, silicone is incorporated into a surface-active agent, with a polyoxyalkylene portion of the molecule and/or a hydro-carbon portion of the molecule. As will become clear, this results in severalunique properties of the surfactant. It has been understood that simply usingsilicone surfactants and traditional hydrocarbon-based surfactants in mixturesresults in unpredictable results. Hill (15) reports that the behavior varies fromantagonistic (positive nonideal) to synergistic (negative nonideal). Incorporation

Specialty Silicone Conditioning Agents 213of the hydrocarbon group into a silicone surfactant overcomes the interactionswhich provide nonideal performance in blended systems. Table 2 shows the product classes available to the formulator both in sili-cone-based products and in the more traditional hydrocarbon products. Theintroduction of the functionalities onto the silicone backbone results in mul-tifunctional products with a unique combination of properties. In order to prepare silicone surfactants, one needs a raw material ontowhich the functional group can be placed. Two silicone polymers are used,dimethiconol (also known as silanols) and dimethicone copolyols, both ofwhich contain reactive hydroxyl groups.2. Properties/ApplicationsThe following silicone surfactants illustrate the new properties that are attain-able when one combines silicone and classical surfactant technologyI. Silicone Complexes1. Structure/BackgroundFatty quaternary compounds commonly are used in conditioning applicationsand are discussed elsewhere in this book. While they are well accepted in manyapplications, there are some areas in which improvement of properties wouldbe of interest to the formulator. These include the following. 1. Fatty quaternary compounds are incompatible with anionic surfactants, since an insoluble complex is frequently formed when the two types of materials are combined (16). 2. The use concentration of many fatty quaternary compounds is limited by their irritation properties (17). At concentrations of 2.5%, most quats are minimally irritating to the eyes (18); but they are more irritating as the concentration increases. 3. Fatty quats are generally hydrophobic and when applied to substrate render the substrate hydrophobic. This can cause a loss of water absor- bance of the substrate. It is not an uncommon situation for a traveler to a hotel to encounter a very soft towel that totally fails to absorb water. This is because the fatty quaternary gives softness but, being hydropho- bic, also prevents rewetting. This situation also can be observed on hair: the conditioner becomes gunky on the hair and has a tendency to build up. Many of these negative attributes have been mitigated by making siliconecomplexes with carboxy silicone compounds (19). The carboxy silicone com-plexes with quaternary compounds have altered properties that make themhighly desirable in personal care applications. In order to study the complexes,

214 O'LenickTable 3 Carboxy Silicone Fatty Quat ComplexesCTFA name Fatty quat Stearlkonium chlorideStearlkonium dimethicone copolyol phthalate Cetyltrimonium chloride(referred to as SDCP) (referred to as CETAC)Cetyl trimethylammonium dimethiconecopolyol phthalate (referred to as CDCP)the following quaternary compounds were chosen as controls. Stearalkoniumchloride is an excellent conditioning agent, having outstanding substantivityto hair. It has detangling properties and improves wet comb when applied aftershampooing. The FDA formulation data for 1976 reports the use of this ma-terial in 78 hair conditioners, 8 at less than 0.1%, 18 at between 0.1% and 1.0%,and 52 at between 1% and 5%. Cetyltrimonium chloride, or CETAC, is a verysubstantive conditioner which in addition to having a nongreasy feel, improveswet comb and also provides a gloss to the hair. It is classified as a severe pri-mary eye irritant (20). Therefore its use concentration is generally at or below1%. These materials were complexed with a carboxy silicone to form clear,water-soluble complexes. These complexes provide outstanding wet combproperties, antistatic properties, and nongreasy softening properties to hair,and fiber and skin. They are minimally irritating to the eye and can be used toformulate clear conditioners. The carboxy silicone fatty quat complexes areshown in Table 3.2. Properties/ApplicationsFatty quat/carboxy silicone compounds are easily formulated into a variety ofpersonal care products, without emulsification, the use of elaborate thickeningsystems, or homogenization. Carboxy/quat complexes are amenable to a vari-ety of physical forms used in personal care products. They can be formulatedinto shampoos, gels, mousses, exothermic conditioners, and virtually any otherform of product desired. They provide a number of beneficial properties, suchas compatibility with anionic surfactants, lower irritation, and good combingproperties. Traditional fatty quats, like stearlkonium chloride and cetyltrimoniumchloride, form water-insoluble complexes when combined with sodium laurylsulfate in aqueous solution. This is due to the formation of an anionic/cationiccomplex that is insoluble. CDCP, like the traditional quats, forms an insolublecomplex, but surprisingly, SDCP is compatible and clear, as shown by thefollowing test. A 10% solids solution of sodium laruryl sulfate (28%) was

Specialty Silicone Conditioning Agents 215Table 4 Compatability of Quats with Anionic SystemsQuat Endpoint ObservationStearalkonium chloride 0.3 mL White solidCetyltrimonium chloride 0.2 mL White solidCDCP 0.5 mL White solidSDCP 35.8 mL Haze developsTable 5 Eye Irritation of Selected QuatsMaterial Result InterpretationCetyltrimonium chloride 106.0 Severely irritatingCDCP 8.3 Minimally irritatingStearalkonium chloride Severely irritatingSDCP 116.5 Minimally irritating 11.3prepared. Separately, a 10% solids solution of the quat compound was pre-pared. The quat is titrated into 100 mL of the sulfate solution. The formationof a white insoluble complex, or the formation of a haze, is considered theendpoint of the titration. As can be seen from Table 4, SDCP is unique in thatit is compatible with anionic systems. Eye irritation is a major concern in the formulation of personal care prod-ucts, particularly when working with quats. Primary eye irritation was testedusing the protocol outlined in FHSLA 16 CFR 1500.42. The products weretested at 25% actives. The results are reported in Table 5. It should be noted that at a concentration of 0.5%, stearalkonium chloridewas minimally irritating. This rating of minimally irritating was the same as forCDCP and SDCP at 25% (or 50 times the concentration). As the data clearlyshow, the irritation potential of the complex is dramatically reduced, whencompared to the starting quat. The ability of hair to be rewetted is an important factor in selecting condi-tioning agents. This makes them different from the standard fatty quats, whichmake the substrate hydrophobic and gunky. When fatty quaternary compoundsthat have been complexed with carboxysilicone are used to treat hair, theymake hair soft, but they do not make the hair hydrophobic. Perhaps most important in the context of this book is the outstanding effectthe incorporation of the silicone complexes has on both wet and dry combing.Compounds made using this complexation technology give outstanding wetand dry combing properties to hair.

216 O'LenickJ. Silicone Phosphate Esters1. Structure/BackgroundA series of silicone surface-active agents containing an ionizable phosphategroup has been developed. These silicone-based phosphate esters and theirderivatives are the topic of numerous patents (21). The properties have beencompared to and contrasted with traditional fatty phosphate esters (22). Thestructures of the silicone phosphate esters are as follows:2. Properties/ApplicationsSilicone-based phosphate esters are substantive to hair, skin, and fiber andprovide antistatic properties. Since these compounds contain a pendant ioniz-able phosphate group, they provide antistatic and lubrication properties to thehair or fiber. Silicone phosphate esters are acidic and can be neutralized to any desiredpH with alkaline materials. The pH of the final formulation not only affectsthe solubility of the phosphate ester, but also has a profound affect on othersurfactant properties such as wetting, foaming, and emulsification. The par-tially neutralized phosphate ester has solubility characteristics between that ofthe free acid and the completely neutralized phosphate ester. As emulsifiers,silicone-based phosphate esters are efficient, producing emulsions of the oil-in-water type. They are very useful as emulsifiers for personal care applica-tions, such as moisturizing creams and lotions. They are particularly effectivein producing creams and lotions containing sunscreens (both organic andinorganic), pigments, skin protectants, and medicaments. The emulsification

Specialty Silicone Conditioning Agents 217properties allow for the use of these materials in one-step shampoos and otherapplications, including emulsion polymerization processes. As water-soluble emollients, silicone phosphate esters can be used in aque-ous systems. For example, they can be added to carbomer gels for emolliencywithout diminishing the clarity of the gel. The phosphating of dimethiconecopolyol renders the molecule more water soluble, necessitating fewer molesof ethylene oxide for the same degree of water solubility. This allows for re-tention of much of the favorable esthetics associated with the increased con-tent of the dimethylpolysiloxane portion of the molecule. As foaming agents, silicone-based phosphate esters produce higher levelsof copious foam than are produced by dimethicone copolyols. The sodium andpotassium salts of the phosphate esters tend to be slightly better foamingagents than the phosphate esters in their free acid or amine salt form. Saltsformed by the neutralization of dimethicone copolyol phosphate and myris-tamidopropyldimethylamine are excellent foam boosters and conditioners inshampoo systems. Salts formed by the neutralization of dimethicone copolyolphosphate and linoleylamidopropyldimethylamine are excellent emulsifiersfor dimethicone in shampoo systems. As detergents, silicone-based phosphateesters show good detergency: surface tension reduction, wetting, emulsifica-tion, dispersing properties, and solubilization. Their detergent properties aregenerally considered to be equal to those of nonionic surfactants; however, thepresence of the silicone in the molecule results in improved mildness, substan-tivity, and conditioning properties over conventional fat-based phosphateesters. These properties make the products excellent candidates for incorpo-ration into shampoos and other detergent systems for personal care. Silicone-based phosphate esters can function as hair conditioners and have been foundto have outstanding conditioning affects when applied to permed hair. A dou-ble-blind, half-head study was conducted on female subjects having permedand nonpermed hair. Subjects were instructed to apply conditioners aftershampooing on wet hair, leave in for 2 min, and then rinse. After dry combing,no difference in conditioning was perceived by the subjects with unpennedhair. However, a dramatic difference was observed by all subjects havingpermed hair. The side where the dimethicone copolyol phosphate-containingconditioner was used showed greatly improved body, curl retention, and man-ageability compared to the side where the conditioner without the dimethi-cone copolyol phosphate was applied. It was concluded that dimethiconecopolyol phosphate is a highly efficacious material for conditioning permedhair. a. Toxicity. Silicone phosphate esters have been found to have a low orderof toxicity. They are nonirritating to the skin when evaluated by FHSLS 16CFR15 00.41 for primary skin irritation, giving values of zero. They are non-

218 O'LenIckirritating to the eyes when evaluated by FHSLS 16 CFR 1500.41 for primaryeye irritation, giving values of zero. They are nontoxic when evaluated by FHSLS16 CFR 1500.41 for acute oral toxicity, having LD50 values above 5 g^g. Theyare also noncomedogenic when evaluated using a standard comedogenicityassay. This profile suggests that these materials are outstanding candidates forpersonal care applications. b. SPFEnhancement. Dimethiconecopolyol phosphate has been demon-strated to boost the SPF of chemical sunscreens by as much as 47%, and non-chemical or pigmented sunscreen systems by as much as 17% (23). It has beenpostulated that the superior wetting properties of the dimethicone copolyolphosphate allows the sunscreening materials to cover the skin more efficiently,in a thinner, more uniform film. c. Typical Formulations. Silicone phosphate esters find applications ina variety of personal care products. Their properties as outlined abovemake them excellent additives for hair care, skin care, and other personal careapplications.K. Other Silicone Esters1. Structure/BackgroundTwo new classes of silicone based esters have recently been prepared. The firstclass of materials is prepared by the esterification reaction of a dimethiconoland a fatty acid (24). These dimethiconol esters contain both a fatty group anda silicone polymer group. They conform to the following structure:Me Me MeIIICHj(CH2),-C(0)-0~Si—0-(-Si—O).—SI-0-C(OHCH2)iCH3I IIMe Me Me The second class results from the reaction of a dimethicone copolyol witha fatty acid (25). The dimethicone copolyol group initially contains a siliconegroup and a polyoxyethylene group. The incorporation of the fatty group bythe esterification reaction results in a product that has a water-soluble, a sili-cone-soluble, and a fatty-soluble group present in one molecule. This class ofcompounds conforms to the following structure:

Specialty Silicone Conditioning Agents 219 Me Me Me Me Ii I IMe-Si—0-~(-Si--0),—(-Si—)b--0—Si—Me II I I Me Me (Cllih Me I 0-(CH2CHjO).(CH2CH(CH,)0),(CH2CHiO).C(0)-R2. Properties/ApplicationsTypical properties of this class of compounds are as follows. Dimethiconol stearate. A water-insoluble, nonocclusive, highly lubricious silicone was. The physical form is a white pastelike wax, which liquiefies under pressure. It has been used in personal care applications, including dispersing of pigments such as titanium dioxide and zinc oxide for sun- screen products, and in many other applications. This is a dimethiconol- based compound. Dimethicone copolyol stearate. This material forms a microemulsion in water with no added surfactant. The product is a liquid. It is highly lubricious and tends to stay at the interface of water and glass. The product has been used as a hair conditioner, and in a variety of emulsification appli- cations. This is a dimethicone copolyol-based compound. To illustrate the range of solubilities achievable using this technology, products were tested at 5% solids. Table 6 illustrates that silicone can be chosen for inclusion in a particularformulation by considering the phase in which the formulation can use thebenefit of silicone. It can be added as an emulsion to the phase in which thesilicone functionality is desired. For example, if you want the silicone in the oilphase to effect pay off of an oil-in-water emulsion, pick a silicone soluble inthe oil phase. If you want silicone in the aqueous phase to affect the spread-ability of the emulsion, pick a water-soluble silicone. You may also pick asilicone that is insuiuble in either phase. In addition to two distinct families ofproducts which are prepared using fatty acids, two distinct classes of productsare made from natural triglycerides. These materials provide conditioning,gloss, and softening properties when applied to the hair or skin. Products derived from many other triglycerides are also available. Siliconederivatives from these function in formulations in the same manner as siliconeproducts made from the analogous fatty acids, and are used predominantly fortheir name on the label. For example, dimethicone copolyol cocoabuteratemight be a good additive for after-sun products. For deodorant sticks, dimeth-icone copolyol isostearate provides slip and negates the soapy feel of the

220 O'LenIckTable 6 Solubilities of Products 5% productSolvent Dimethiconol Dimethicone copolyolWater Insoluble DispersibleMineral spiritsSilicone fluid (350 cs) Soluble InsolublePolyethylene glycol (PEG 400) Dispersible InsolubleGlycerol trioleateOleic acid Insoluble DispersibleMineral oil Insoluble Soluble Dispersible Soluble Dispersible Insolublesodium stearate. For day creams, dimethiconol stearate forms a hydrophobic,nonocclusive film on the skin. Dimethiconol fluoroalcohol dilinoleate is aunique fluorosilicone wax which provides outstanding barrier properties.IV. CONCLUSION AND FUTURE DEVELOPMENTSA recent publication (26) suggests that the balance between the oil-solubleportion, the silicone-soluble portion, and the water-soluble portion of a sili-cone surfactant is critical to the functionality. This relationship among thethree different phases has been explored in a concept called three-dimensionalHLB. The development of this concept promises to offer new assistance in thepreparation of emulsions. In summary, new silicone polymers are used in manydiverse application areas in the personal care market. There has been plethoraof new silicone compounds that contain portions of the molecule that is notsilicone based. These non-silicone groups in the molecule can be hydrocarbonbased, polyoxyalkylene based, or based on other classes of raw materials. Thenew polymers have unique properties, partially contributed by the silicone andpartially contributed by the other groups. Silicone compounds are not just oilphases any more. More work is expected on the application of these materialsto different formulations. The future of these types of compounds in personalcare applications will depend on the ability of companies to create the newcompounds and the ability of creative formulators to utilize the compounds.REFERENCES 1. U.S. Patent 3,964,500 (1976). 2. U.S. Patent 4,741,855 (1988). 3. U.S. Patent 5,100,657 (1992).

Specialty Silicone Conditioning Agents 221 4. U.S. Patent 5,100,658 (1992). 5. U.S. Patent 5,100,646 (1992). 6. U.S. Patent 5,106,609 (1995). 7. Di Sapio A. Soap Cosmet Chem Spec 1994; 70(9). September. 8. O'Lenick AJ Jr, Parkinson JK. J Soc Cosmet Chem 1994; 45:247-256. 9. Dhams G, Zombeck A. Cosmetc Toilet 1995 (Mar.); 110:91-100.10. U.S. Patent 3,661,964 (1972).11. U.S. Patent 5,378,787 (1995).12. Dhams G, Zombeck A. Cosmet Toilet 1995 (Mar.); 110:91-100.13. Hunter A. In: Encyclopedia of Conditioning Rinse Agents. Micelle Press, 1983: 174-175.14. Ibid., p. 99.15. Hill R. ACS Symp Ser 1992; 501:278.16. Dhams G, Zombeck A. Cosmet Toilet 1995 (Mar.); 110:91-100.17. Ibid.18. U.S. Patent 5,070,171 (1991).19. O'Lenick A Jr, Sitbon Suserman C. Carboxy silicone quaternary complexes. Cos- met Toilet 1996 (Apr.); 111:67-72.20. O'Lenick A Jr, Parkinson JK. J Soc Cosmet Chem 1994; 45:247-256.21. Ibid.22. O'Lenick A Jr, Parkinson JK. Phosphate esters: chemistry and properties. Textile Color Chem 1995; 27(ll):17-20.23. Imperante J, O'Lenick A Jr, Hannon J. Dimethicone copolyol phosphates to in- crease sun protection factor. Soap Cosmet Chem Spec 1996; 76(5):54-58.24. U.S. Patent 5,051,489 (1991).25. U.S. Patent 5,180,843 (1993).26. O'Lenick A Jr, Parkinson JK. Cosmet Toilet 1996 (Oct.); 111:37^4.

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10Cationic Surfactants and QuaternaryDerivatives for Hair and Skin CareMatthew F. Jurczyk, David T. Floyd,and Burghard H. GruningGoldschmidt Chemical Corporation, Hopewell, VirginiaI. INTRODUCTIONQuaternary ammonium compounds have traditionally been utilized for emul-sified hair conditioners. Later advances led to the development of quaternar-ies, which were less irritating and are compatible with shampoos and liquidsoap detergents. These innovations paved the way for commercial applicationsin skin care creams and lotions. This chapter presents the definition, development, and application of qua-ternary derivatives for the personal care industry.A. Quaternary Ammonium SaltsBy general definition, quaternary ammonium salts are \"a type of organic com-pound in which the molecular structure includes a central nitrogen atomjoined to four organic groups as well as an acid radical\" (1). At least one ofthese substitution groups is typically hydrophobic in nature. Quaternary de-rivatives based on fatty acids, proteins, sugars, and silicone polymers are allused in the cosmetic industry. Quaternary ammonium salts are cationic sur-face-active compounds and adsorb readily onto surfaces such as hair and skin. It is the ability to adsorb onto substrates which makes,the use of cationicsurfactants so widespread. By 1996, one trade directory alone listed over 300commercially available cationic surfactants and over 200 nitrogen-based am-photeric surfactants (2,3). 223

Figure 1 Representative amines. R = an organic radical based on one or morecarbon atoms. (From Ref. 4.)B. AminesFatty alkyl-substituted amines form the base intermediate for most catiomcsurfactants. Representative examples are shown in Figure 1. The number of radicals combined with the nitrogen atom determines theorder of substitution. These designations are known as primary (mono-substi-tuted), secondary (di-substituted), and tertiary (tri-substituted). Primary aminesare also used as intermediates in the preparation of diamines (4). Quaternary ammonium salts are formed by the reaction of amines withalkylating agents such as methyl chloride, methyl sulfate, or benzyl chloride.Representative quaternaries are shown in Figure 2.C. Amphoteric SurfactantsA related class of amine derivatives are nitrogen-based amphoteric and zwit-terionic surfactants. Zwitterionic materials have both a positive and a negativecharge at their isoelectric point. Amphoteric surfactants are characterized bya molecular structure containing two different functional groups, with anionicand cationic character, respectively (5). Most amphoteric surfactants behavein acidic mediums as cationic surfactants, and in alkaline medium like anionicsurfactants. The alkyl betaines and alkylamido betaines are different in thatthey cannot be forced to assume anion-active behavior through an increase inpH value (6,7). While these compounds can function and are stable over awide pH range, they exhibit cationic tendencies in acidic systems (8). Examplesinclude alkyl betaines and alkylamido betaines, carboxylated imidazoline de-rivatives, and amphoacetates. These are shown in Figure 3. One characteristic of cationic surfactants is that they tend to form insolublesalts (precipitates) in combination with anionic surfactants, such as fatty alco-hol sulfates. Amphoteric surfactants, however, remain clear in anionic systems

Catlonic Surfactants and Quaternary Derivatives 225 CHj X>ehlortda;X could b* + X'chlorlda or methyl (ulfataCHj-N-R nwthyl sulfate on sonw quatemariM CHj—N-CH3 ^ R • allphaltei aaturatad or CH3 R unaatuiatsd, normal or Ra aliphatic saturatsd or branched, C | - C a unaaturated, C12- Ca chain lanathaMonoalkyi Trimathyl Quatamary Ammonium Chloride DIalkyI Dimethyl Qualameiy Ammonium Chloride«-|-. X'chloride CH, ^H, X'chlorhte R-N-CH,-CHj-CHi-N-CHi R • illphetlc, eiturated R> aliphatic, alkyl, normal or branched, CH] CH3 oruntaturatad CfC^gTrIalkyI Methyl Quttemaiy Ammonium Chloride Complex Oiqualernery Ammonium Chloride Alkyl Benzyl Dimethyl Quaternary Ammonium ChlorideFigure 2 Representative quaternary types. (From Ref. 4.)and are said to be \"anionic compatible.\" This feature, along with their abilityto enhance formula viscosity, mitigate irritation, and impart skin softness, hascontributed to the increasing popularity of nitrogen-based amphoteric surfac-tants in the personal care industry.D. Amine OxidesAmine oxides are another group of quasi-cationic, nitrogen-based productswhich display anionic surfactant compatibility. Amine oxides are prepared byAlkyl Dimethyl Betalne Alkyllminodiproplonate Alkoamphoglyclnate, A d d pH • (DIcarboxylate) Catlonic Form Catlonic at Acidic pH ConditionsFigure 3 Representative amphoteric surfactants. (From Ref. 112.)

226 Jurczyk et al. CH3R-N-^O I CH3Figure 4 Cocamine oxide. R represents the alkyl groups derived from coconutoil. (From Ref. 113.)reacting tertiary amines with hydrogen peroxide. They are nonionic at alkalinepH conditions, but gain positive charges and exhibit cationic activity in acidicsolutions. Although they have been incorporated into shampoos and otherpersonal care products, amine oxides play their greatest commercial role inhousehold, industrial, and institutional cleansers. See Figure 4.E. AmidoaminesAmidoamines are an interesting class of substances characterized by the pres-ence of one or more amide groups coupled with one or more amine functions.When compared to alkyl amines and their derivatives, amidoamines are gen-erally more compatible with anionic surfactants, easier to formulate with, andfunction as better foaming aids (9). Representative amidoamine compoundsand related derivatives are displayed in Figure 5.II. HISTORICAL DEVELOPMENT OF THE CATIONIC SURFACTANT INDUSTRYGroundwork for the commercial development of cationic surfactants was laidin the early years of the twentieth century, when Einhorn described the anti-Cocamldopropyl Coeamidopropyl Betalne Coeamidopropyl Ethyl Dimethylamlne Dimonium EthosulfateFigure 5 Representative amidoamine derivatives. (From Ref, 113.)

Catlonic Surfactants and Quaternary Derivatives 227microbial properties of quaternary salts. This was followed by the first publi-cation on the use of a quaternary as a surgical antiseptic in 1936 (10). Significant toxicological data were also compiled during the early postwarperiod. Cutler and Drobeck noted that benzalkonium chloride appeared to beone of the most widely studied quaternaries between 1940 and 1950. Cutlerfurther attributed this intense scrutiny to the proliferation of quaternary ger-micides in a wide range of industrial and household applications. Theseincluded farm disinfectants, industrial disinfectants, skin antiseptics, mouth-washes, and diaper sanitizers (11). During the 1930s, other applications for cationic surfactants were beinginvestigated. 1939 marks the first commercial production of long-chain fattyamines for an industrial application (potash flotation). Commercial proce-dures for the production of quaternary salts continued to be developed andrefined in the 1940s. By the early 1950s, quaternaries such as dihydrogenatedtallow dimethyl ammonium chloride were found in widespread industrial ap-plications, ranging from organoclay additives for drilling muds to consumerfabric softeners, and eventually hair conditioners. Institutional acceptance of quaternary ammonium compounds paved theway for their incorporation into the first personal care products. The timingof their commercial introduction (the late 1940s) coincided with a surge inmarket demand for hair conditioners used to mitigate damaging effects ofpopular permanent waves. While commercial hair conditioners had beenavailable as early as the 1930s, development of a truly substantive cationicconditioner was not possible until the advent of stearalkonium chloride in1946. Originally developed for the textile industry, this ingredient was readilyadapted by cosmetic formulators and for many years was the workhorse ofcream rinse formulations (12). Further industry refinements have been directed at enhancing the compatibil-ity of quaternary ammonium salts and other cationic derivatives with anionic sur-factants. While true cationic surfactants are suitable for use in hair dyes, cremerinses, and some hair grooming preparations, their irritancy and incompatibil-ity with anionic surfactants traditionally limited their potential for inclusion inhigh-foaming mass market shampoos, skin cleansers, and bath preparations. In the early 1970s, a number of conditioning shampoos, based on polymericquaternary ammonium resins such as polyquatemium 7 and polyquaternium10, and polyethylene imines were introduced (13). Opportunities for incorpo-ration of conventional quaternary ammonium salts in anionic shampoo sys-tems, however, remained limited. In 1970 Jungerman commented that qua-ternary ammonium compounds with three or four long alkyl chains had not\"attained any scientific or industrial significance\" (14). Within 15 years, this situation had changed dramatically. Procter & Gamblehad patented the technology for a conditioning shampoo containing a \"tri long

228 Jurczyk et al.chain alkyl mono short chain alkyl quaternary ammonium salt. . . togetherwith a dispersed insoluble silicone phase\" (5,16). Today, tricetylmonium chlo-ride is prominent on the ingredient labels of brands which, when combined,account for over 30% of the U.S. shampoo market (17). Other approaches aimed at improving quaternary compatibility with an-ionic surfactants resulted in the development and use of amphoteric imida-zoline derivatives and cocamidopropyl betaine in a wide range of \"mild\" babyshampoos and skin cleansers. Betaines and imidazoline were found to be ex-tremely effective in reducing irritancy while enhancing foam and viscosity per-formance. Their incorporation in cleansers and mild shampoos has greatlyadvanced the use and market acceptance of nitrogen-containing compoundsin the personal care industry. While the earliest quaternaries were originally developed for use in indus-trial applications and \"adopted\" by the personal care industry, many of thelatest innovations have been synthesized specifically to satisfy unmet consumerneeds. As the industry matures and becomes even more highly segmented,competition and the need to satisfy consumer expectations will continue to bea driving force behind the new technical innovations. A discussion of recentinnovations is presented elsewhere in this chapter.III. CATIONIC SURFACTANT CHEMISTRY AND FUNCTIONALITYThe main groups of cationic surfactants are alkylamines, alkyl imidazolines,ethoxylated amines, and quaternaries. These organo-modified polymers havebeen reviewed and will be further examined in this chapter (18-21).A. AlkylaminesAlkylamines form a fairly large group of cosmetic surfactants. Alkylaminesand their salts form a group in which the amino function is responsible for thesurface-active properties and the water solubility of the compound. Primary,secondary, and tertiary alkylamines, with their salts and substances containingmore than one basic nitrogen atom, are included in this group. Alkylamines in this group possess long alkyl chains and are relatively hy-drophobic. Their salts with inorganic and strong organic acids exhibit the typeof solubility required for amphiphiles. These alkylamines are commonly pre-pared by reduction of the corresponding acylamide via the nitrile to the amine. The synthesis of these alkylamines first requires the reaction of an acidchloride with 1 mole of a simple or substituted diamine to yield a series ofsubstances sometimes referred to as \"amido-amines.\" These substances aremore polar than the straight-chain uninterrupted alkylamines and are more

Cationic Surfactants and Quaternary Derivatives 229widely used in cosmetics as cationic emulsifiers. As a rule, these amines formprecipitates with the more commonly used anionic surfactants. The free amines in this group are waxy solids, while the salts and the inter-rupted amines exhibit higher melting points. The positive charge carried bythe neutralizing amines is responsible for their substantivity to negativelycharged biological surfaces, such as skin and hair. These amines—usually in the form of salts from phosphoric, citric, or aceticacid—are used in cosmetics primarily in combination with fairly hydrophilicsurfactants. The interrupted alkylamines are compatible with a variety of othersurfactants. The interrupted allq'lamines can be used, e.g., in combination withglyceryl monostearate to form emulsions with good tolerance to electrolytes.In lotion formulations, the interrupted amines prevent an increase in viscosityupon standing. Aqueous solutions formed by the acid-derived amine salts areeffective hair conditiners and have antistatic properties. Examples of these types of amines are presented in Figure 6.R-CH2NH2 \"-\"'OH. Afkylamtne Dimethyl Alkylamine Acylamidopropyldlmethylamlne LactateFigure 6 Examples of alkylamines.

230 Jurczyk et al.UCH3(CH2)i6-T^ N-CH2CH2OH Stearylhydroxyethyl ImidazolineFigure 7 Typical alkyl imidazoline.B. Alkyl ImidazolinesThe alkyl imidazolines comprise a small group of basic heterocyclic substances.They are obtained by the reaction of aminoethylethanolamine with a suitablefatty acid. An example is given in Figure 7. During this synthesis, no linearamide is formed, but it is cyclized to a five-membered substituted ring. Thefcarboxy-carbon of the fatty acid becomes part of this ring. For the sake ofsimplicity, the nomenclature retains the name of the originally employed fattyacid, although the pendant group has been shortened by one carbon atom.Reaction of the alkyl imidazoline with an alkylating agent opens the ring andyields the amphoteric derivatives of ethylenediamine. The compounds in thisgroup are all l-hydroxyethyl-2-alkyl imidazolines. The alkyl imidazolines are liquids and normally distributed as aqueous so-lutions. Imidazolines themselves are not used widely in cosmetics. Amphotericsurfactants, however, can be derived from fatty imidazolines. They are em-ployed in aqueous media. Imidazolines are subject to hydrolysis to the amide,and re-formation of the cyclic structure is probably pH dependent. It has notbeen established whether the cyclic imidazolines or their hydrolysis productsconstitute the active species. A structure for a fatty imidazoline is given in Figure 8. Four types of amphoterics are derived from a fatty imidazoline compoundby a reaction from acetate or propionate, giving rise to monoacetate, diacetate,monopropionate, and dipropionate amphoterics (Figure 9) (22).

Cationic Surfactants and Quaternary Derivatives 231MonoacetateDIacetateMonopropionate RCONH(CH2)2 -N—(CH2)2— COO\" Na* (CH2)20HDipIrnopthioenaUte.S. market, t(ChrHe2e)2tCraOdOit'ional amphNoat*erics are used in most mildshampoosR: CdOisNodHi(uCmH2c)2o-cNo—am(CpHh2o)d2i-a0c—e(tCatHe,2)s2o-CdiOumO' lauroamNpah*oacetate, anddFisgoudrieum9 laFuoruoratmyppehsoodfiamcepthaotete. rWicsh.ile these are mild surfactants, their poten-tial for conditioning is minor. They are selected for use mainly for irritationreduction and mitigation potential. They are most widely used in formulationsfor baby shampoo and personal cleansing.C. Ethoxylated AminesThe ethoxylated amines constitute a group of nitrogen-containing surfactantsin which the aqueous solubility is to a large extent dependent on the degreeand type of alkoxylation. The basic nature of the amino group is not readilydisplayed in those substances, which carry long-chain polyoxyethylene (POE)groupings. The simple POE amines are prepared from long-chain alkyl amines by eth-oxylation. In some cases, the alkylamine is converted to a diamine beforeethoxylation (Figure 10).

232 Jurczyk et al. PEG-n Alkyiamine{x + y has an average value of n)Figure 10 Ethoxylated amine. A more complex type of alkoxylated amine (the poloxamine) is synthesizedby reaction of ethylene diamine with propylene oxide (Figure 11). This resultsin the formation of a hydrophobic tetra-substituted ethylene diamine. Whenthis is then reacted with ethylene oxide, its hydrophobicity is decreased, de-pending on the ration of hydrophobe to hydrophile. Even more complicated,Figure 11 Poloxamine.

Catlonic Surfactants and Quaternary Derivatives 233Figure 12 Alkoxylate amine.terminally fatty alkyl-substituted alkoxylated amines have been prepared, suchas a PEG-n tallow polyamine (Figure 12). Most ethoxylated amines are water soluble and are compatible with a widevariety of other surfactants, including anionics. They are relatively weak basesand do not require large amounts of acids to adjust their pH to the rangenormally used in cosmetics. Ethoxylated amines are waxy solids which melt at relatively low tempera-tures. Ethoxylated amines are used as emulsifying and hair conditioning agents.They also can be used to aid in the dispersion of solids. Some members of thisclass increase product viscosity, while others are used to improve foaming. Thesubstances making up this class are acid and alkali stable and are not subjectto hydrolysis.D. QuaternariesWhile quaternary salts can be produced from the alkylation of primary orsecondary amines, in commercial practice tertiary amines are typically em-ployed (see Figure 13). This is done to reduce the need for excess alkylatingreagent and limit the formation of free amine (5).Tertiary Amine + Methyl Chloride - Quaternary Ammonium ChlorideFigure 13 Quaternary synthesis.

234 Jurczyk et al. The presence of an unreacted alkylating agent and a free amine are unde-sirable. To eliminate free amine, manufacturers acidify their product. Thisresults in the formation of an odorless amine salt. It is important to recognizethat since commercial quaternary ammonium compounds always containamine salts, any formulation at alkaline pH conditions would result in odor,emulsion instability, and irritation problems stemming from reconversion ofthe amine salt to its free amine form. Development chemists must thereforemaintain acidic pH conditions in their formulas (23).E. Miscellaneous CatlonlcsNo discussion of quaternary ammonium salts and cationic surfactants in thepersonal care industry would be complete without mention of the introductionof new derivatives which are based not on traditional animal or vegetable-based fatty substances, but on a wide range of natural and synthetic feedstocks. During the 1960s, the substantivity and conditioning effects of collagen-derived polypeptides on hair were described and cosmetic proteins were in-cluded in shampoos, conditioners, permanent waves, bleaches, and other haircare preparations (24). The positive perception and consumer acceptance ofcosmetic proteins led to the introduction of quaternized collagen hydrolysatesby the early 1980s (25). Similar advances were made using silicone technology. The acceptance of silicones by the cosmetic industry is substantiated by the increase in sales from only a few tons in the early 1970's to tens of thousands of tons in the 1990's. The development of amphoteric, amono functional and quaternized silicone derivatives offered a new range of mild products with improved aesthetic properties, including superior gloss, combing, and conditioning of hair. These compounds have also found a niche in the skin care industry where they can be used to enhance spreadability with reduced tackiness in creams and lotions (15). The use of naturally derived glucose and hydroxyl substitutions has contrib-uted to the relatively recent acceptance of quaternary ammonium derivativesin skin care applications. For instance, products such as lauryl methyl gluceth10 hydroxypropyldimonium chloride are promoted for their ability to enhanceskin moisturization (26). Cationic oil-in-water emulsifiers such as dipalmitoyl-ethyl hydroxyethylmonium methosulfate can be used to enhance skin soften-ing, lubricity, and emolliency (27).F. Function of Quaternary Compounds on HairDaily hair care no longer encompasses just the cleansing of hair, but the ex-pectation that attributes such as static control and conditioning will be realized(28). These expectations encompass a large number of attributes, most of which

Cationic Surfactants and Quaternary Derivatives 235are closely related to Robbins et al.'s definition of the term \"hair manageabil-ity\" (29). An attribute that is closely associated with conditioning is ease ofcombing. An mstrumental technique has been established to obtain a quanti-tative measure of this parameter (30).The isoelectric point of untreated hair is pH 3.7 (31). This indicates that thehair surface attains a cationic charge at a pH under 3.7 while assuming ananionic character above that pH. Traditionally, quaternary ammonium salts(or quats) have been used as the main additive responsible for conditioningeffects. Their structure can be represented as , where R isa long-chain alkyl group, X is the counteranion, and a is the number of alkylgroups attached to the quaternary nitrogen atom. There are, of course, manytypes of quaternized compounds that can be used in hair treatment, and theireffects can be varied. Quaternary ammonium compounds have been found to be efficient at de-positing on hair as well as improving combability. Adsorption has been attrib-uted to an electrostatic attraction between the anionic character of the hairfiber and the positively charged quat molecule (32-34). Hair has been de-scribed as being a \"strong-acid ion exchanger,\" and one can expect somedesorption of the quat upon rinsing with detergents. In addition to electro-static forces, attraction owing to van der Waals forces has also been shown toplay a part in the adsorption process (35). Increasing the number of alkylgroups, as well as increasing the length of the carbon chains on the quat, hasbeen shown to be beneficial for the conditioning of hair (32,36). If the cationiccharge character is responsible for bringing the quat to the hair surface, it isthe long-chain alkyl groups that are believed to be responsible for lubricity andcombing performance. Lunn and Evans (37) postulated that there are threeprincipal factors which contribute to the \"fly away\" problem of hair or staticcharge effects. The first is the magnitude of charge which is generated by thecontact and subsequent separation of hair and comb. The second factor is themobility of charge and its rate of dissipation from the fibers. The third factoris the distribution of charge along the length of the combed fibers. In principle,the desired objective of reduced electrostatic effects can be approached byaltering each of these factors. Either a reduction in the magnitude of chargegenerated or an increase in the mobility of that charge can be effective. Mutualrepulsion of fibers can also be altered by changing the distribution of chargedensity along the length of the fiber. The generation of static charges arises from an unequal transfer of chargesacross the interface between two bodies in contact when unlike objects arerubbed together. When the bodies are separated, they are each left with netcharges of opposite sign and of magnitude equal to the differential chargetransferred. Theoretical aspects of this process are discussed by Bick (38),Arthur (39), and Hersh and Montgomery (40). The charge generated by rubbing

236 Jurczyk et al.filaments together has been studied experimentally by Hersh and Montgomery(41). Henry et al. (42) measured both charge magnitude and the rate of itsdecay from rubbed textile fabrics. Barber and Posner (43) measured thecharge generated by combing human hair. Mills et al. (44) also attempted tomeasure the charge generated by combing hair, but the method employed didnot permit a distinction to be made between generation and dissipationmechanisms. The distribution of charge along the length of a fiber, although noted byBallou (45) as important, has received very little investigation. The only dis-cussion of such phenomena is by Sprokel (46), who studied the variation ofcharge along a running textile yam. The charge generated on the hair by combing was found to be of positivesign for typical hair treatments and for all comb materials examined (37). Thisfinding is consistent with two factors. First, keratin is at or near the positiveend of the triboelectric series (47), and when it is rubbed against other mate-rials which are lower than keratin in the series, a positive charge is developedon the keratin. [It is possible by certain treatments to alter the position ofkeratin in the triboelectric series (48).] Second, when two bodies are rubbedtogether under conditions where the bodies contribute unequal areas to therubbing surface, the body which contributes the larger area tends to developa positive charge (49). When hair is combed, it is the hair which contributesthe larger area of contact. When the experimental evidence was examined for these three chargeproperties of hair (37), it was found all of these need to be considered to fullyunderstand the action of antistatic agents. The charge generated by combing and the half-life of charge mobilityboth decrease with increasing relative humidity. The increased charge mobil-ity is clearly a consequence of the greater water content at higher humidities,although the exact relationship is not well understood and other factors arealso involved (50). Increased mobility of charges on the fiber leads to a de-crease in the charge generated by combing, because of the charge conductionalong the fibers as they are rubbed. This mechanism has been postulated toexplain the decrease of generated charge with increasing relative humidity(40). When a large concentration of a quaternary ammonium compound is pre-sent on the hair fiber, the surface conductivity is substantially increased. Thenegligible charge generated under such circumstances can be explained by thishigh conductivity and by the mechanism of charge conduction along the fibers.However, when the quaternary is rinsed off with water before drying, so thatonly small quantities remain on the fiber, the charge generated by combingremains relatively low, even though the charge half-life increases substantiallyand is comparable to that of untreated hair. The reduced charge generated

Cationic Surfactants and Quaternary Derivatives 237cannot be explained by a mechanism of enhanced surface conductivity. Analternative mechanism must be sought. It was hypothesized that the reduction of charge generated by combing,when hair is treated with quaternary ammonium compounds, is due primar-ily to the lubricating properties of these compounds on the dry hair, ratherthan to the enhanced conductivity. The quaternary acts as a lubricant andreduces tangling, so that the force required to pull a comb through the hairis substantially reduced, especially the end peak force. The reduced nor-mal contact force between hair and comb leads to a reduced charge on thehair. Medley (51) postulated that an antistatic agent need not be present as acontinuous film in order to be effective. A discontinuous film would not givelong-range conductivity and, therefore, the half-life of charge mobility wouldremain high. Medley proposed a mechanism requiring only localized conduc-tivity at the contact site. This mechanism could be acting as a secondary effect.Another secondary effect could be a change in the chemical nature of the fibersurface, which would alter the magnitude of charge generated. Lunn and Evans(37) believed that the reduction of combing force by lubrication is the primarymechanism involved. We now know that quaternary ammonium antistatic agentsdo not normally achieve their effect by mechanisms of increased conductivityor of charge dissipation. Their primary effect is a lubricating action, whichreduces substantially the force required to comb hair, especially the end peakforce. The reduced normal contact force between hair fibers and comb leadsto a reduction of static charge generated on the hair. The adsorption on hairof long-chain alkyl quaternary ammonium salts, cationic polymers, and com-plexes of cationic polymers with anionic polymers or anionic detergents canproduce significant changes in the electrochemical surface potential of thefiber. This results in different charging characteristics in relation to polymersand metals. The effect of treatments such ad dyeing, bleaching, and permanentwaving was also explored. Apart from altering the electrochemical potential,surface modification may also affect the conductivity of fibers (37,52).Modification of hair surface by reduction, bleaching, and oxidative dyeing re-sults in very small changes of charging characteristics as compared to untreatedfibers. They also have an insignificant effect on the fiber conductivities at lowhumidity. During combing, such parameters as fiber elongation, stress, and magni-tude of frictional forces between the comb and fiber undergo variations duringthe movement of a comb from the upper point of a tress toward the fiber tips.Consequently, nonuniform distribution of triboelectric charge density alongthe length of the fiber tress is usually observed (37). This might also effect thecorrelation between surface modification and triboelectric charging and leadto quantitatively different results.

238 Jurczyk et al.G. Formulating with Quaternary Compounds1. Hair CareThe chemistry of quaternary ammonium salts and allied nitrogen derivativesencompasses a broad range of structural variations. This versatility enableschemists to \"custom tailor\" formulas by selecting specific ingredients accord-ing to their performance characteristics. When formulating cosmetic products with quaternary compounds, it is nec-essary to consider the effect of ingredient structure and molecular weight onparameters of solubility and compatibility (i.e., with anionic surfactants, salts,esters, bases, foam generation, and irritation). Factors such as ingredient sub-stantivity (including buildup with prolonged use) and effect on moisture re-tention are also extremely important considerations for the formulation ofboth hair and skin care products. One must also consider the effect functional ingredients have on hair ten-sile strength, combing performance, detangling performance, static (flyaway),and cuticle damage. Although individual cosmetic companies and testing labo-ratories may vary their procedures slightly, clinical and in vitro evaluation pro-tocols for these parameters are well established and thoroughly described inthe literature. Robbins offers a detailed treatment of this topic (53). The number and chain length of fatty alkyl groups and the presence ofhydroxyfunctional linkages have a direct bearing on the functional propertiesof quaternary salts. Short-chain (up to 16 carbon atoms) mono-alkyl quater-naries and ethoxylated quaternaries (i.e., cetrimonium chloride, PEG-2 coco-monium chloride, PEG-2 stearmonium chloride) are generally water soluble,whereas other mono-, di-, and tri-alkyl quaternaries (i.e., steartrimonium chlo-ride, distearyldimonium chloride, tricetylmonium chloride) are not (54). In one study, blond hair tresses were treated with test quaternary com-pounds, then rinsed, dried, and immersed in an anionic tracer dye. Tressestreated with dialkyl quaternary salts displayed greater color development, sug-gesting greater cationic substantivity, than tresses treated with monoalkyl orethoxylated quaternaries. Studies involving solvent extraction of quaternarysalts from treated hair tresses corroborated this finding. Detangling propertiesof quaternary ammonium salts also appear to be directly proportional tonumber and carbon chain length of the fatty moieties. See Figure 14 (55). In a separate study, the ability of various conditioning agents to reducestatic flyaway of hair was tested using a shadow silhouette hair tress method: For the measurement, every hair tress was combed with a coarse, sawed comb. With a punctual source of light (diameter 0.6 cm) the hair tress produced a silhouette on a screen in a distance of 15 cm. On this screen, concentric semi circles were marked [Figure 15]. The tip of the uncharged hair tress coincides with the centre of the semi-circle. In the shadow of the fixing point a ruler was attached to the screen so

Catlonlc Surfactants and Ouatamary Dadvativaa 239Key: 5-Strong ^ Normal Hair 1-Weak Waved HairFigura 14 Detangling properties of quaternary salts. (From Ref. 32.)that it could rotate. The ruler was turned to the silhouette so that the left and rightborder of the hair tress was marked. Then the radius of the semi-circle to which theruler built a tangent, was read off. The sum of both radii results in the measuredvalue, the stronger is the fly-away effect, caused by the elearostatic charge trans-ferred to the hair by combing.Rgura 15 Flyaway cffea measuring method. (From Ref. 56.)

240 Jurczylt tt al. SHADOW SILHOUETTE METHOb 110 170 Less Fly Away Than Control Greater Fly Away Than Control Fly-Away Effect [arbitrary units]Figure 16 Flyaway effect by electrostatic charge. (From Rcf. 56.) Comparative hair static control data using selected quaternary, betaine,amidoaminc salt, and polyquatemary species are shown in Figure 16. Tlieshorter the bar, the less electrostatic charge is caused by combing (56).2. Skin CareWhenever creams and lotions are formulated, cosmetic chemists must payparticular attention to concerns pertaining to irritation and ingredient com-patibility. Even though cationic emulsifiers can be balanced with anionic fattyacids to produce stable soap emulsions, cationic agents are normally precipi-tated by anionic emulsion stabilizers. Cationic emulsifiers do offer certain advantages over anionic and non-ionic components in the formulation of certain skin care products. Lanzet, inDeNavarrc's book, states: \"The pH of normal skin is 4.2-4.6. . . . Cationicemulsifiers are very compatible with the acid mantle and help to maintain itwhile anionic surfactant systems may promote keratin swelling and overtax ortemporarily inactivate the buffering capacity of the skin, thus leading to irri-tation and lessened resistance to infection.\" Clationic and amphoteric surfac-tants are also compatible with quaternary germicides (57).

Catlonic Surfactants and Quaternary Derivatives 241 Many materials, such as polycationic resins, polymer complexes, cationicpolysaccharides (including polycationic cellulose), cationic guar gum, etc., canbe used by formulators to bridge problems associated with ingredient compati-bility (58-68). Such anionic compatible cationics can now be found in manyskin cleansers, which are themselves based on inexpensive, high-foaming, an-ionic surfactants. One example cites the use of a cationic guar gum to improveconsumer skin feel of a bar soap (69). Related patents describe the use of otherhydrated cationic polymers to improve mildness (67,70). In a completely dif-ferent new personal wash application, cationic polymers are employed to en-hance functional ingredient deposition on skin (71).IV. COMMERCIAL APPLICATIONSQuaternary ammonium salts and related surfactants continue to play a vitalrole in the development of new hair and skin care products. A search of U.S.patents between 1986 and 1996 yielded no fewer than 300 citations of cationicor quaternary hair- or skin care-related patents. These citations attest to thecontinuing evolution of quaternary ammonium salt technology. For instance,one example describes the preparation of quaternary ammonium substitutedsaponin esters derived from soy or ginseng feedstocks. These materials areclaimed to offer excellent static control and improved conditioning benefits(72).A. Hair CareLong-chain mono- and dialkyl quaternary ammonium salts have been longrecognized for their ability to improve hair texture and control static. Fattyalcohols are used together with such quaternaries in hair conditioners to im-prove smoothness and softness. One drawback to such systems is that they maydisplay undesirable sticky or oily side effects. These problems can be mitigated,even on very dry hair, by using a branched quaternary ammonium salt in com-bination with a polyethylene glycol Ce-Cio alkyl ether (73). Branched quaternary compounds have been demonstrated to offer otherbenefits to the cosmetic formulator. Stearyl octyl dimonium chloride (Figure17) was found to offer comparable wet combing, dry combing, and static con-trol compared to two unbranched quaternaries (dicetyldimonium chloride andstearlkonium chloride) in hair tress studies using bleached, waved hair. Thisingredient was found to be water soluble and liquid at room temperature inconcentrations suitable for use in clear cream rinses, conditioners, and pumpsprays (74). Similar benefits are cited in the use of isostearamidopropyl quaternary am-monium compounds. Isostearyl feedstocks are natural liquids at ambient con-

242 Jurczyk et al.Figure 17 Stearyl octyldimonium chloride. (From Ref. 113.)ditions, even though they are fully saturated. Ulike oleyl compounds, whichare unsaturated, isostearyl derivatives are not subject to color degradation andrancidity concerns (75). Alkylamidopropyl functions can be used to overcome disadvantages asso-ciated with long-chain fatty quaternaries. Typical problems associated with theuse of quaternary compounds include anionic incompatibility, buildup on hair,negative efect on foam, and/or hazing in clear systems (76). Amidoamine saltscan also be used to overcome these problems. Amidoamine salts also displaya reduced tendency to build up on hair and can offer better \"body\" than theirquaternary ammonium counterparts (77). One of the more active areas of contemporary cosmetic technology is theuse of silicones and silicone functional quaternary derivatives (78). Siliconepolymers are used to improve lubricity, gloss, combing, and manageability inhair care products (79). They offer good surface tension modifications andremain fluid, even at high molecular weights. It is not surprising that a widerange of modifications can be made from them (18). A recent search of the literature uncovered examples of silicone ampho-terics (80,81), silicone betaines (82), silicone phosphobetaines (83,84), siliconealkyl quaternaries (85), silicone amido quaternaries (86), silicone acetate qua-ternaries (87,88), silicone imidazoline quaternaries (89), and silicone carboxyquaternaries (90). Compared to organic quaternary saUs, silicone quaternary derivatives aredistinguished by the fact that they impart a \"silklike feeling\" to hair (91). Thesynthesis and preparation of polyquaternary polysiloxanes are described bySchaefer (92). One commercial example is shown in Figure 18. Janchitrapon-vej employs a silicone quaternary, together with an amidoamine salt, in theformulation of a clear hair conditioner (93,94). Another interesting application for this type of polyquaternary siloxane iscited by Schueller et al. This patent describes the use of a diquatemary poly-dimethylsiloxane as the primary dispersant of water-insoluble silicone oils inaqueous hair care preparations, such as shampoos and conditioners. Silicone

Catlonic Surfactants and Quaternary Derivatives 243 R' = CocosFigure 18 Quaternium 80. (From Ref. 19.)oils can \"provide the hair with a silky, lubricious feel.\" While this silicone qua-ternary imparts substantivity and conditioning, its function as a silicone oildispersing agent is unique and not typical of other commercially available qua-ternary hair conditioning agents (95). O'Lenick describes the preparation of a quaternary containing both sili-cone and protein functional groups. The high-molecular-weight siloxane link-age contributes to oxidative stability and mildness, whereas the protein moietycontributes to film formation on hair and skin. Since such compounds arenonvolatile and display inverse cloud point characteristics, they are claimed tobe ideally suited for use in personal care products (96). Further discussion of the use of silicones in personal care products can befound in another chapter of this volume.B. Skin CareSun care and tanning continue to be among the fastest-growing segments ofthe personal care industry. Several patents suggest the potential for use ofquaternary salts ofpara-dialkyl amino benzamide as a new generation of non-irritating sunscreen actives (97,98). Another reference explores the possibilityof binding cationic moieties to UV absorbers in order to enhance substantivityto skin (99). In yet another application, quaternary ammonium salts are incorporatedtogether with indole compounds to promote sunless tanning. \"It is believedthat melanin is an oligomer containing several indole segments formed bycyclization and polymerization of dihydroxy phenylalanine (DOPA) caused byexposure to the sun.\" Schultz et al. note, therefore, that indole compounds arebeing investigated for their potential applications in the self-tanning industry.The main problem associated with indoles as tanning enhancers is that theyfacilitate a color change slowly. It has been discovered that the formation ofmelanin to color the skin can be catalyzed by the use of quaternary ammonium

244 Jurczyk et al.salts. Indole/quatemary salt combinations are said to impart a deep, long-last-ing tan which forms on the skin within 2 hr of application and exposure tosunlight (100). Cationic emulsifiers do play an important role and can offer specializedbenefits for cosmetic and pharmaceutical formulators. For instance, Papadakisdescribes the preparation of systems based on quatemized phosphate esters,such as linoleamidopropyl PG-dimonium chloride phosphate. These formulasdisplay exceptional stability at acidic pH conditions and may be used in thepreparation of cosmetics containing alpha-hydroxy acids (101). Zeigler notesthat it is possible to prepare exceptionally mild, freeze-thaw-stable systemsusing combinations of quaternary ammonium functionalized phosphate esterstogether with cationic polysaccharides (102). A European publication cites use of alkylamines and derivatives such ascholesteryl betainate in the formation of cationic oil-in-water emulsions fordrug delivery systems. Cationic emulsions are said to be less likely to coalescein the presence of sodium and calcium ions which are present in physiologicalfluids. Furthermore, these systems demonstrate enhanced affinity to biologi-cal membranes and can be used to facilitate the delivery of cosmetic (i.e.,antioxidants, anti-free radicals, sunscreens) and pharmaceutical (i.e., steroidantiinflammatory drugs, beta-blocking agents for glaucoma treatment, antibi-otics) agents (103). Multiple watcr-in-oil-in-water (W/O/W) emulsions (Figure 19) with aternary phase structure can be used to encapsulate active ingredients forcontrolled release in skin care and pharmaceutical preparations. Amphotericand zwitterionic surfactants, such as lauramidopropyl bctaine and dimethi-Figure 19 Structure of the interfaces in ternary emulsions. (From Ref. 104.)

Cationic Surfactants and Quaternary Derivatives 245cone propyl PG betalne, have been demonstrated to be effective hydrophilicstabilizers in such systems (104). Wilmsmann's patent outlines the preparation of cationic oil-in-water emul-sions based on a fatty acid salt, hydroxyethyl-ethylenediamine. This system issaid to be highly substantive to skin, thereby forming a protective barrier againstorganic and alkaline irritants (105).V. FUTURE DEVELOPMENTS AND CONCLUSIONSWhile it is problematic at best to predict the course of future developments inany scientific field, an inspection of current patents and publications offers aglimpse into emerging technologies and market applications. Most recentwork in this field seeks to understand the physiological effect of cationic sur-factants in the context of pharmaceutical research. The following studies sug-gest that in the future we may see greater use of cationics in consumer oralcare and medicated skin treatment preparations. Cationic surfactants and nitrogen derivatives may play a role in facilitatinghealing. Examples include the use of amphiphatic peptides to stimulate fi-broblast and keratinocyte growth (106) and use of \"a skin protein complexingcomposition for the potentiation of the substantivity of aluminum acetatethrough the use of a cationic emulsifier\" (107). Quaternized proteins in com-bination with anionic polymers have also been shown to be useful in treatingkeratinic substances (108). Ledzy describes the use of a cationic quaternaryammonium salt to increase the penetration of a pharmaceutical compositioninto skin (109). Therapeutic studies involving the use of nitrogen-derived surfactants in oralcare products are related to skin and pharmaceutical research. Polefka notesthe importance of including a zwitterionic surfactant (in this case lauramido-propyl betaine) as a stabilizing agent in a mouth rinse containing a cationicantimicrobial aid (bis-quanide) together with anionic anticalculus agents(110). Muhlemann (111) states that cationic diamine salts can be used to stabilizethe hydrolysis of tin salts in aqueous and oral care compositions. The cationicadditive preserves, and may even potentiate, the inhibiting action of the tinsalts on plaque formation and dental caries. An extensive volume of recent data also continues to document benefits forcationic surfactants in the field of sanitation. While this topic is beyond thescope of this chapter, it will nevertheless have a significant impact on the futuremarketability and consumption of cationics. In conclusion, any survey of cationic surfactants, quaternary ammoniumsalts, and related nitrogen derivatives can include only a small sample of

246 Jurczyk et al.developments in the field. The authors hope that the reader will use the ref-erences cited to explore this topic in further detail.REFERENCES 1. G. Hawley, ed. The Condensed Chemical Dictionary. 10th ed.. New York: Van Nostrand Reinhold, 1981:877. 2. McCutcheon's Emulsifiers and Detergents. Vol. 1. Glen Rock, NJ: Manufacturing Confectioner PubUishing Co., 1996. 3. McCutcheon's Emulsifiers and Detergents. Vol. 2. Glen Rock, NJ: Manufacturing Confectioner Publishing Co., 1996. 4. Sherex fatty amines and diamines. Technical bulletin. Greenwich, CT: Witco Corp., undated. 5. Bluestein BR, Hilton CL. Amphoteric Surfactants. Vol. 12. New York and Basel: Marcel Dekker, 1982. 6. Moore CD. J Soc Cosmet Chem 1960; 11:13. 7. Ploog U. Seifen-Ole-Fette-Wachese 1982; 108:373. 8. J.M. Richmond, ed. Cationic Surfactants. Vol. 34. New York: Marcel Dekker, 1990:175. 9. Ibid., p. 51.10. Jungerman E, ed. Cationic Surfactants, Vol. 4. New York: Marcel Dekker, 1970: 493.11. Ibid., p. 528.12. DeNavarre MG. The Chemistiy and Manufacture of Cosmetics. Vol. 4. Carol Stream, IL: Allured Publishing Co., 1975:1102.13. Gerstein T. Cosmet Perfum 1975 (Mar.); 90:38.14. Jungermann E, ed. Cationic Surfactants, Vol. 4. New York: Marcel Dekker, 1970: 29.15. Procter & Gamble. U.S. Patent 4,704,272.16. Procter & Gamble. U.S. Patent 4,788,006,17. Branna T. HAPPI1995 (Dec); 32:80.18. Floyd D. Cosmetic and Pharmaceutical Applications of Polymers: Organo-Modi- fied Silicone Copolymers for Cosmetic Use. New York: Plenum Press, 1991:49.19. Floyd D, Jenni K, Polymeric Materials Encyclopedia. Vol. 10. New York: 1996: 7677.20. O'Lenick A. Cosmet Toilet 1994; 109:85.21. O'Lenick A. Cosmet Toilet 1996; 111:67.22. Schoenberg T. Cosmet Toilet 1996; 111:99.23. Gerstein T. Cosmet Toilet 1979 (Nov.); 94:35,24. Balsum MS, Sagarin A, eds. Cosmetics, Science and Technology. Vol. 2, New York: Wiley Interscience,, 1972:348.25. Stern ES, Johnsen VL. Cosmet Toilet 1983 (May); 98:76.26. Technical Bulletin, Edison, NJ; Americhol Corporation, 1993.27. Dunn CA. HAPPI 1996 (May); 33:126.28. Nanavati. J Soc Cosmet Chem 1994; 45:135.

Cationic Surfactants and Quaternary Derivatives 24729. Robbins CR, Reich C, Clarke J. Hair manageability. J Soc Cosmet Chem 1986; 37:489-499.30. Garcia ML, Diaz J. Combability measures on human hair. J Soc Cosmet Chem 1976; 27:379-398.31. Jachbwicz J, Berthiaume MD. Heterocoagulation of silicon emulsions on keratin fibers. J Colloid Interface Sci 1989; 133:118-134.32. Jurczyk M. Cosmet Toilet 1991 (Nov.); 106:63.33. Weatherburn AS, Bayley CH. The sorption of synthetic surface-active compounds by textile fibers. Textile Res J 1952; 22:797-804.34. Loetzsch KR, Reng AK, Gantz D, Quack JM. The radiometric technique, explained by the example of adsorption and desorption of \"C-labeled distearyl-dimethylam- monium chloride on human hair. In Orfanos CE, Montagna W, Stuttgen G, eds. Hair Research: Proceedings of the International Congress, 1979. Berlin: Springer- Verlag, 1981:638-649.35. Robbins CR. In Chemical and Physical Behaviour of Human Hair. New York: Van Nostrand Reinhold, 1979: chap 5.36. Spiess E. The influence of chemical structure on performance in hair care prepa- rations. Parfuem Kosmet 1991; 72:370-376.37. Lunn O, Evans D. J Soc Cosmet Chem 1977; 28:549.38. Vick FA. Theory of contact electrification. Br J Appl Phys 1953; suppl 2:S1-S5.39. Arthur DF. A review of static electrification. J Textile Inst 1955; 46:T721-T734.40. Hersh SP, Montgomery DJ. Static electrification of filaments: theoretical aspects. Textile Res J 1956; 26:903-913.41. Hersh SP, Montgomery DJ. Static electrification of filaments: experimental tech- niques aned results. Textile Res J 1955; 25:279-295.42. Henry PSH, Livesey RG, Wood AM. A test for lability to electrostatic charging. J Textile Inst 1967; 58:55-77.43. Barber RG, Posner AM. A method for studying the static electricity produced on hair by combing. J Soc Cosmet Chem 1959; 10:236-246.44. Mills CM, Ester VC, Henkin H. Measurement of static charge on hair. J Soc Cos- met Chem 1956; 7:466-475.45. Ballou JW. Static electricity in textiles. Textile Res J 1954; 24:146-5.46. Sprokel GJ. Electrostatic properties of finished cellulose acetate yarn. Textile Res J 1957; 27:501-515.47. Shashoua VE. Static electricity in polymers: I. Theory and measurement. J Polymer Sci 1958; 33:65-85.48. Landwehr RC. Electrostatic properties of corona-treated wool and mohair. Textile Res J 1969; 39:792-793.49. Gruner H. An investigation of the mechanism of electrostatic charging of textile fibers. Faserforsch Textiltech 1953; 4:249-260.50. Shashoua VE. Static electricity in polymers: II. Chemical structure and antistatic behavior. J Polymer Sci 1963; Al:169-187.51. Medley JA. The discharge of electrified textiles. J Textile Inst 1954; 45:123- 141.52. Jachowicz J. J Soc Cosmet Chem 1985; 36:189.

248 Jurczyk et al.53. Robbins CR. Chemical and Physical Behavior of Human Hair. 2d ed. New York: Springer-Verlag, 1988.54. Jurczyk MF, Berger DR, Damaso AR. Cosmet Toilet 1991 (Apr.); 106:63.55. Ibid., p. 67.56. Leidreiter HI, Jenni K, Jorbandt C. S G F W J1994; 120:856.57. DeNavarre MG, ed. The Chemistry and Manufacturing of Cosmetics, Vol. 3. Carol Stream, IL: Allured Publishing Corp., 1975:385.58. Helene Curtis. U.S. Patent 5,417,965,59. Calgon. U.S. Patent 5,338,541.60. Conopco. U.S. Patent 5,338,540.61. Helene Curtis. U.S. Patent 5,221,530.62. Clairol. U.S. Patent 4,911,731.63. Henkel. U.S. Patent 4,900,544.64. Chesebrough Ponds. U.S. Patent 5,169,624.65. L'Oreal. U.S. Patent 5,008,105.66. ICI Americas, Inc. U.S. Patent 5,112,886.67. Procter & Gamble. U.S. Patent 5,064,555.68. Hi-Tek Polymers, Inc. U.S. Patent 5,009,969.69. Procter & Gamble. U.S. Patent 4,946,618.70. Procter & Gamble. U.S. Patent 5,296,159.71. Cheseborough Ponds. U.S. Patent 5,543,074.72. Pacific Chemical. U.S. Patent 5,182,373.73. KAO. E.P. Patent 046887A1.74. Jurczyk MF. Cosmet Toilet 1991 (Nov.); 106:91.75. Gesslein BW. J Soc Cosmet Chem 1990 (May); 66:37.76. Smith L, Gesslein BW. Alkylamidopropyl dihydroxypropyl dimonium chlorides. Technical bulletin. Inolex Chemical Corp.77. Schoenberg T, Scafidi A. Cosmet Toilet 1979 (Mar.); 94:57.78. Floyd D. Silicone Surfactants: Applications in the Personal Care Industry. New York: Marcel Dekker. In press.79. Floyd D, Leidreiter H, Sarnecki B, Maczkiewitz U. Preprints 17th IFSCC Con- gress, Yokahama, 1992:297.80. Siltech. U.S. Patent 5,073,619.81. Goldschmidt. U.S. Patent 4,609,750.82. Goldschmidt. U.S. Patent 4,654,161.83. Siltech. U.S. Patent 5,091,493.84. Siltech. U.S. Patent 5,237,035.85. Siltech. U.S. Patent 5,098,979.86. Siltech. U.S. Patent 5,153,294.87. Goldschmidt. U.S. Patent 4,833,225.88. Goldschmidt. U.S. Patent 5,891,166.89. Siltech. U.S. Patent 5,196,499.90. Siltech. U.S. Patent 5,296,625.91. Meyer H. CTMS 1990 (Jan.); 15:5.92. Goldschmidt. U.S. Patent 4,891,166.93. Helene Curtis. U.S. Patent 5,556,615.

Cationic Surfactants and Quaternary Derivatives 249 94. Helene Curtis. U.S. Patent 5,328,685. 95. Alberto Culver. U.S. Patent 5,306,434. 96. Siltech. U.S. Patent 5,243,028. 97. ISP Van Dyke. U.S. Patent 5,451,394. 98. ISP Van Dyke. U.S. Patent 5,427,774. 99. Pacific Chemical. U.S. Patent 4,987,183.100. Clairol. U.S. Patent 5,049,381.101. Helene Curtis. U.S. Patent 5,567,427.102. Chesebrough-Ponds. U.S. Patent 5,135,748.103. AM RCS. Dev. Co. W.O. Patent 93/8852 4155.104. Hameyer P, Jenni K. Perf Kosmetic 1994; 75:844.105. Donald Basiliere. U.S. Patent 5,229,105.106. Demeter Biotechnologies. U.S. Patent 5,561,107.107. C. Fox et al. U.S. Patent 4,879,116.108. L'Oreal. U.S. Patent 4,796,646.109. J. Ledzy et al. U.S. Patent 5,346,886.110. Colgate. U.S. Patent 5,180,577.111. GABA International. U.S. Patent 4,828,822.112. Miranol technical and product development data. Technical bulletin, Rhone Poulenc, 1985.113. Wenninger JA, McEwen AN, eds. International Cosmetic Ingredient Dictionary, 6th ed.. Vol. 1 & 2,1995.

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11Polymers as Conditioning Agentsfor Hair and SkinBernard IdsonUniversity of Texas at Austin, Austin, TexasI. INTRODUCTIONOne class of conditioning agents is cationic (positively charged) quaternaryammonium salts, in which the cationic portion contains the surface active por-tion. Improvement of conditioning effects on hair and skin has been achievedby virtual replacement of monomeric quaternary ammonium compounds bycationic polymers. Polymers find their chief use as substantive conditioningagents in hair. However, a number of cationic resins find value in skin carebecause of their emollient smooth feel on the skin (1). Noncationic polymersare also finding a place as conditioning and substantive agents for skin andhair. Included in this review are historical development, the physicochemical andstructural bases for cationic polymer conditioning and substantivity, and dis-cussion of the multiplicity of cationic polymers in primarily hair and secondar-ily in skin conditioning, including quaternized synthetics, cellulose derivatives,quatemized guar, lanolin, animal and vegetable proteins, substantive condi-tioning humectants, and aminosilicones.A. Polymers (General)The terms polymer, high polymer, and macromolecule are used to designatehigh-molecular-weight materials. Polymers can be natural, synthetic, or bio-synthetic. A biosynthetic polymer is a natural polymer which has been modi-fied with one or more synthetic functional groups. 251

252 Idson Two major types of polymerization methods are used to convert smallmolecules (monomers) into polymers. These methods were originally referredto as addition and condensation polymerization. Addition polymerization isnow called chain, chain-growth, or chain-reaction polymerization. Conden-sation polymerization is now referred to as step-growth or step-reactionpolymerization. The monomers normally employed in addition reactions contain a carbon-carbon double bond that can participate in a chain reaction. The mechanismof the polymerization consists of three distinct steps. In the initiation step, aninitiator molecule(s) is thermally decomposed or allowed to undergo a chemi-cal reaction to generate an \"active species.\" This \"active species,\" which canbe a free radical, a cation, an anion, or a coordination complex, then initiatesthe polymerization by adding to the monomer's carbon-carbon double bond.The reaction occurs in such a manner that a new free radical cation, anion, orcomplex is generated. The initial monomer becomes the first repeat unit in theincipient polymer chain. In the propagation step, the newly generated \"activespecies\" adds to another monomer in the same manner as in the initiation step.This procedure is repeated over and over again until the final step of the proc-ess, termination, occurs. In this step, the growing chain terminates throughreaction with another growing chain, by reaction with another species in thepolymerization mixture, or by the spontaneous decomposition of the activesite. Two or more different monomers are often employed in a chain-reactionpolymerization to yield a polymer containing the corresponding repeat units.Such a process is referred to as copolymerization, and the resulting product iscalled a copolymer. By varying the copolymerization technique and the amountsof each monomer, one can use as few as two monomers to prepare a series ofcopolymers with considerably different properties. The amount of differentmaterials that can be prepared increases dramatically as the number of mono-mers employed increases. Thus, it is not too surprising that the majority ofsynthetic polymers used today are copolymers. Condensation polymerization normally employs two difunctional mono-mers that are capable of undergoing typical organic reactions. For example, adiacid can be allowed to react with a diol in the presence of an acid catalyst toafford a polyester. In this case, chain growth is initiated by the reaction of oneof the diacid's carboxyl groups with one of the diol's hydroxyl groups. The freecarboxyl or hydroxyl group of the resulting dimer can then react with an ap-propriate functional group in another monomer or dimer. This process is re-peated throughout the polymerization mixture until all of the monomers areconverted to low-molecular-weight species, such as dimers, trimers, tetramers,etc. These molecules, which are called oligomers, can then react ftirther witheach other through their free functional groups. Polymer chains that have

Polymers as Conditioning Agents 253moderate molecular weights can be built in this manner. The high molecularweights common to chain-reaction polymerizations are usually not reached.This is due to the fact that as the molecular weight increases, the concentrationof the flee functional groups decreases dramatically. In addition, the groupsare attached to the ends of chains and, hence, are no longer capable of movingfreely through the viscious reaction medium. What makes polymers so \"different\"? A polymer's unusual physical behav-ior is due to the tremendous amount of interactions between its chains. Theseinteractions consist of various types of intermolecular bonds and physical en-tanglements. The magnitude of these interactions is dependent on the natureof the intermolecular bonding forces, the molecular weight, the manner inwhich the chains are packed together, and the flexibility of the polymer chain.Thus, the amount of interaction is different in different polymers and quiteoften different in different samples of the same polymer.B. Cationic Polymers for ConditioningA great improvement in recent years has been the introduction into shampoosof cationic compounds, the hydrophilic functional groups of which are no longerat the end of the fatty chain but inserted within a polymeric structure, wherebypotential for irritation is far reduced as compared with conventional products.Such resins, formerly used in setting lotions for their hair-holding properties,can be combined with amphoteric and nonionic surfactants, and some showremarkable compatibility with anionics, which is the most required propertyboth for good foaming and cleaning power and for economic reasons. Cationic polymers are a type of substantive raw material commonly used inhair-conditioning formulations. They are made by attaching quaternized fattyalkyl groups to modified natural or synthetic polymers. While structurally simi-lar to quats, they have many more cationic sites per molecule and much highermolecular weights. Once deposited, cationic polymers provide hair with slip, manageability,and good combability. They increase body in damaged hair, spread well andevenly, and can improve split ends. Their relatively high activity, which allowslow use levels, and compatibility with anionic surfactants when properly for-mulated, make them ideal conditioning agents. A potential drawback of usingcationic polymers is their tendency to build up with repeated usage. This canweigh the hair down and give it an unappealing look and feel. Cationic polymers can be made from a variety of synthetic as well as naturalpolymers, such as guar gum and cellulosics. A polymer's physical character-istics vary according to the monomer and monomeric ratios used in its manu-facture. Molecular weight is another factor affecting the polymer's physicalcharacteristics and performance properties.

254 Idson Proteins, polypeptides derived from various plant and animal sources, arecommon conditioning agents. Because of their similarity to the protein-aceous structure of hair and skin, they are naturally adsorbed. Once depos-ited, proteins are said to improve surfaces by attaching to the damaged sites.Also, their substantivity can be enhanced through reaction with quaternizedmaterials.II. HISTORICAL DEVELOPMENTEarly hair preparations contained shellac fixatives. The disadvantage, primar-ily sticky, hard-feeling hair, provoked formulation of shampoos with softerfeels (conditioning) containing cationic surface-active agents. These surfac-tants are classified according to the charge on the hydrophobic (water-repel-lant) portion. Anionic surfactants possess a negative charge; RCOO\" (R isusually a fatty acid from carbons 12-18). Cationic surfactants bear a positivecharge. They are principally quaternary ammonium compounds, R4N'^X\"(monomeric) or (polymeric). By virtue of their positive surfacecharge, they have a great affinity to negatively charged keratin in hair and skin,the basis of their conditioning and substantive properties. Most cationic poly-mers do not build up on the hair and are not as irritating. They do not interferewith foaming or cleaning as do fatty chain cationics (2). Cationic polymers aresoluble in water with varying degrees of substantivity and are compatible withanionic, cationic, and amphoteric surfactants and electrolytes (see SectionIII).Cationic polymers, proteins, and amino acids are very efficacious condition-ing agents because of their substantivity to hair. Some studies suggest thatamino acids will actually penetrate into the hair and increase the moisturecontent as well. Proteins and cationic polymers typically remain on the fibersurface, reducing combing forces and flyaway, and in some systems they pro-vide enhancement of volume and body and an improvement in manageability.These ingredients may be found in shampoo formulations in concentrationsranging from 0.5% to 10.0%. Silicones may be incorporated into shampoos inthis same concentration range to reduce eye irritation, combing forces, staticcharge, and drying times while increasing foam stability, body, shine, and man-ageability, depending on the particular silicone materials chosen.In addition to hair conditioners, most of the cationic polymers impart smoothfeel, emolliency, and substantivity to skin. Noncationic polymers often servethe same purpose as the charged macromolecule, but in lesser strength.The CTFA Cosmetic Ingredient Handbook Directory defines monomeric cat-ionic surfactants as \"quaternium\" compounds and polymeric quaternary com-pounds as \"polyquaternium\" compounds (3). Detailed descriptions of variedavailable cationic polymers follow in Section IV.

Polymers as Conditioning Agents 255 Shampoos have been formulated with certain cationic polymers such aspolyquatemium 10 (Section IV.K), polyquatemium 7 (Section IV.C), and guarhydroxypropyltrimonium chloride (Section IV.M), which were compatiblewith anionic surfactants in the shampoo formula but became incompatibleupon dilution with water and, as a consequence, were deposited on the hairduring rinsing. The deposit conferred wet combing and styling benefits, but inmany cases these polymers formed extremely stable complexes with hair kera-tin, and with frequent shampooing gave rise to a \"buildup\" that was difficultto remove (4). The buildup may arise from the fact that the polymer-surfactantcomplex has a lower stability constant than the polymer-keratin complexformed at the hair surface and, therefore, the anionic surfactant cannotcompete with the hair surface and, consequently, cannot remove the polymerdeposit. Conditioning shampoos exemplified as \"two-in-one\" or \"three-in-one\"products came into vogue. What makes these multifunctional shampoosattractive to consumers is that they can get cleaning, conditioning (and/or dan-druff control) from a single product in one step. There is now a generation of conditioning shampoos in which the deposi-tion of very hydrophobic materials such as silicones and long-chain alkyl com-pounds are being highlighted. Some products still contain cationic polymerssuch as guar hydroxypropyltrimonium chloride, and some include long-chainalkyl quaternary amines (4),ill. CONDITIONING AND SUBSTANTIVITY FROM CATIONIC POLYMERSCationic polymers are used chiefly in conditioning shampoos for their goodwet combing properties. By choosing the proper polymer/surfactant combina-tion, the complex of cationic polymers and anionics is deposited onto the hairsurface during dilution (water rinsing) to provide lubrication and mending ofdamage (5). The conditioning effect is based on the deposition onto the hair surface orinto the hair fiber of certain functional components that have resistance tosubsequent water rinsing. Since the isoelectric point of hair is approximately3.67, its surface bears a net negative charge near the neutral pH where mostshampoos are formulated. Thus, anionic surfactants bearing a negative chargeare not very substantive to hair and leave the hair in an unmanageable condi-tion (6,7). The improvements in conditioning agents on hair and skin have resulted inmajor replacement of monomeric quaternary ammonium compounds (\"quats\")by cationic polymers, the hydrophilic functional groups of which are no longerat the end of a fatty chain but inserted within a polymeric structure, whereby

256 Idsonthe potential for irritation is reduced. While structurally similar to quats, theyhave many more cationic sites per molecule and much higher molecularweights. About one-third of the quaternary ammonium compounds used to-day for hair and skin care are polymeric in nature. Cationic polymers are characterized by possession of a multiplicity of polarand/or ionic groups which confer water solubility. For adsorption onto keratinto occur there needs to be some attraction between the groups and the keratinsurface. The actual hair conditioner is not the cationic polymer itself but rathera complex of the polymer and the anionic surfactant. While the guidelines for adsorption of surfactants are similar to those ofpolymers, there are differences due mostly to the smaller relative size of thesurfactant molecules. If there are both a cationic polymer and a cationicsurfactant in the solution, there is a competitive adsorption. Due to its rela-tive smallness and high mobility, the surfactant can reduce the uptake of thepolymer. Cationic polymers can be made from a variety of synthetic as well as naturalpolymers, such as guar gum and cellulosics. A polymer's physical character-istics vary according to the monomer and monomeric ratios used in its manu-facture. Molecular weight is another factor affecting the polymer's physicalcharacteristics and performance properties. While all chapters of this volume deal with varied aspects of conditioning,it is worth redefining conditioning in the context of cationic polymers. Schuel-ler and Romanowski (8) note that conditioning, such as with cationic poly-mers, helps hair and skin look and feel better by improving the condition ofthese surfaces. Hair conditioners are intended primarily to make wet hair eas-ier to detangle and comb and to make dry hair smoother, shinier, and moremanageable. Skin conditioners primarily moisturize while providing protec-tion from the drying effects of the sun, wind, and harsh detergents. An ingredient's ability to improve hair or skin condition depends on it beingdeposited onto surfaces and preferably remaining intact, even after rinsing.This resistance to rinse off is known as \"substantivity\" and can be achievedthrough the use of certain raw materials that, because of water insolubility orelectrostatic attraction, stay on the hair and skin. Cationic polymers must be substantive to condition effectively. As with\"quats,\" a polymer's cationic nature allows substantivity via coulombic attrac-tion to anionic surfaces. However, cationic polymers are also used in anionicsurfacant-containing formulas, such as shampoos, where they are solubilizedand expected to wash away during use. However, this does not happen becauseof a unique solubility mechanism. Anionic surfactant systems containing cat-ionic polymers can be designed so that polymers are soluble in the product butbecome insoluble during rinsing and deposit on the hair. This occurs becauseof an association between the cationic polymer and the anionic surfactant in

Polymers as Conditioning Agents 257cosmetic formulations such as shampoos. With excess surfactant, the polymeris solubilized, creating a clear solution. However, during rinsing, the surfactantconcentration falls below the critical level required for solubilization, and thepolymer/surface complex deposits on the hair (8). Once deposited, cationic polymers provide hair with slip, manageability,and good combability. They increase body in damaged hair, spread well andevenly, and can improve split ends. By choosing the proper polymer/surfactantcombination, the complex of cationic polymers and anionics is deposited ontothe hair surface during dilution (water rinsing) to provide lubrication andmending of damage (5). It is known that replacing part of the anionic detergent(s) by amphotericsurfactants dramatically increases the substantivity of cationic cellulose de-rivatives to hair (9). However, too much substantivity can be undesirable be-cause unwanted excessive buildup may occur after repetitive shampooing,leaving hair feeling stiff and heavy. Polyamine derivatives (pseudo-cationicsecondary amines) are also used as conditioning agents. It is claimed that theirweak cationic character does not allow for buildup on the hair shaft, even withrepeated applications (10). Increasing use of silicones has helped avoid build-up. The adsorption of some cationic polymers on hair has been demonstratedto be reduced by addition of small amounts of electrolytes (such as sodiumchloride), which also may partially desorb the adsorbed polymer (11). The adsorption of quaternaries having long-chain fatty portions as part ofthe molecule is the basis for most conditioner formulas. The fatty portion,which is largely not attached to the substrate, acts as a lubricant. The lubricat-ing action makes combing easier. It also allows for detangling of a snarled hairassembly. There is also a degree of hydrophobic bonding in most cases whichis very common. This bonding is of the van der Waals type and has been shownto be very strong. \"Polyquats\" can have multiple-site bonding as well as hydro-phobic bonding. This will bridge or bind along the hair shaft to form a coatingwhich may be filmlike. This film-forming character of certain polyquat resinscauses stiffening of the fiber. Stiffening can be a body-building property (12).The polymers act by adsorbing onto the keratin substrate (hair or skin). Thus,conditioning involves, at least in part, interfacial phenomena in which the sur-face properties of the keratin are altered (13). The conditioning action of any agent may depend on its substantivity oradhesion to hair fibers or on its tendency to interfere with the degreasing ac-tion of pure or modified detergents. In the former case, the presence of theconditioner can be demonstrated with the aid of a labeled conditioner or withthe aid of dyestuffs whose effect on hair is modified by the presence of theconditioning molecule (14,15). Substantivity and film-forming properties make these polyquats excellentcandidates for hair care products. Potential benefits include good set retention,

258 Idsonhigh luster, improved body, and reduced conditioner buildup. Skin condition-ing and fbcative properties contribute to the elegance and permanence of af-tershave or cologne formulas. The moisture barrier and fixative properties ofthese \"polyquats\" also lend themselves to formulation of antiperspirants ordeodorants.A. Skin ConditioningSkin conditioning by cationic polymers has not had the degree of investigationas has had hair conditioning. However, a resin such as polyquaternium 19 findsvalue as a skin conditioner because of its emollient feel on the skin, as well asits substantivity. Substantivity to skin has been demonstrated by liquid scintil-lation counting. Faucher (11) used the same technique to show substantivityto calfskin for polyquaternium 10. Quaterniums 4 and 6, in dry skin lotions, offer a combination of substantiv-ity to the skin with a long-lasting smooth feel. Polyquaterniums 19 and 20 areclaimed to provide polymeric moisture barriers or retard evaporation rates(16). Polymethylacrylaminopropyl trimonium chloride is a functional additivein a wide range of skin care products. Astringents, toners, colognes, andpreshave products prepared with this cationic resin have a silky smooth after-feel (17). Further skin conditioning properties are discussed with individual cationicand noncationic polymers. The adsorption of a cationic polymer on skin showsthe same general behavior as on hair: a sharp initial uptake followed by a slowapproach to equilibrium. Like hair, the mechanism appears to involve slowpenetration of the skin by the polymer, since the uptake by the polymer farexceeds that of a monolayer. It appears that skin keratin is more reactive thanthe harder, more highly crosslinked keratin found in hair.iV. CATIONIC CONDITIONING POLYMERSCationic polymers are available in many forms initiated by PVP (poly-N-vinyl-2-pyrrolidone) and its copolymers (polyquaternium 11,28,16; see Section IV.B).One series of acrylates is (polyquaterniums 5, 6, 7,18,22, 28; Sections D-G,K). There are also quaternized polyvinyl polymers (polyquaterniums 19, 20;Sections G-H) and quaternized lonenes (polyquaterniums 2,17,18, 27; Sec-tion I). Cellulose cationic polymers include polyquaterniums 4,10,24 (SectionK). Polysaccharides such as guar hydrojQ^ropyl trimonium chloride have gainedin popularity (Section M). Natural polymers have been quaternized, such aslanolin and proteins (Section P). Aminosilicones are finding increasing use(Section R).

Polymers as Conditioning Agents 259A. Polyvinylpyrrolidone (PVP)The growth of cationic polymers as hair conditioners was initiated by the in-troduction of PVP (poly-N-vinyl-2-pyrrolidone) in 1950 by then-GAF [nowInternational Specialty Products, ISP (18)] and then by BASF (19). A homo-polymer is a molecule with repeating units of the same molecular structure. Originally developed for incorporating into hairsprays, PVP has been foundto have conditioning properties if applied via a shampoo. The transparent filmon hair imparts smoothness and luster, as well as substantivity, to skin and hair.The films have good holding power and do not flake under moderate climateconditions. PVP has other properties which are used in shampoos and hairconditioners—it improves foam stabilization, increases viscosity and, in cer-tain formulations, can reduce eye irritation (8). Today, PVP is occasionallyused as a conditioning agent in shampoos. However, PVP and its copolymersare used primarily as styling resins. As hair styles continued to progress, some of the deficiencies of PVP ho-mopolymer began to be noticed. PVP is hygroscopic. It tends to become sticky,dull, and tacky as atmospheric moisture is adsorbed, and, of more significance,the adsorbed moisture plasticizes the film and causes ductile fracture of thebond. A further drawback of PVP homopolymer was its tendency to becomebrittle and flaky in dry weather (20).B. Copolymers of PVPMany of the objectionable properties of PVP homopolymer were overcomeby the introduction of PVP random copolymers. A random copolymer tendsto have properties which are intermediate between the properties of thehomopolymers which would be formed by polymerizing the monomers sepa-rately. Thus, a polar hygroscopic homopolymer can be rendered more mois-ture resistant by introduction of a nonpolar comonomer (20).1. PVP/Vinyl Acetate (VA) CopolymersPVPA^A copolymer (Figure 1) was offered as an improved hairspray-condi-tioner (18). Four compositional ratios were offered: 70/30, 60/40, 50/50, and30/70. The higher the ratio of VA, the less susceptible to atmospheric humidityand the harder the film, but consequently it is less easily shampooed off. Thecopolymers used have less moisture sensitivity than PVP, with good hold andgood conditioning. The polymer will also coat the skin, leaving a conditioned,less oily feel (1).2. PVP-a-olefin CopolymersGANEX series (ISP 10) are linear copolymers of PVP and long-chain a-olefins. There are four varieties, differing in the olefin copolymer: P-904 (buty-

260 Idson H2C CHH2 CH3 / \G=0 C=0 N' I I O CH-CH2- I -CH-CHj-Flgure 1 VinylpyrrolidoneAanyl acetate copolymer.lated PVP), V-216 (PVP/hexadecene), V-220 (PVP/eicosene), and WP-660(tricontanyl PVP). They produce smooth substantive coatings on the hair. Theyalso provide a unique \"afterfeel\" in skin care products (18).3. PVP/Methacrylate Copolymers (18) a. Copolymers 845, 937, 958 (ISP). Copolymers 845, 937, and 958 arePVP/dimethylaminoethyl methacrylate (DMAEM) copolymers with var-ied ratios of PVP/methacrylate (Figure 2). They find wide use in blow-dry conditioners as well as conditioning additives in cream rinses and sham-poos. They give a smooth conditioning feel to the skin in creams, lotions, softFigure 2 Vinylpyrrolidone/dimethylaminoethyl methacrylate.

Polymers as Conditioning Agents 261Figure 3 Quaternized copolymers of vinylpyrrolidone and dimethylaminoethylmethacrylate.soaps, shaving products, deodorants, and antiperspirants. Copolymer 845 isslightly cationic and therefore mildly substantive to hair. b. Quaternized PVPIDMAEMA(Pofyquatemium-ll). The cationic polymer,which is most widely used for its conditioning and palliative properties, isprobably polyquaternium-11 [GAFQUATS, ISP (21)]. These compounds arequaternized copolymers of PVP and dimethylaminoethyl methacrylate (Fig-ure 3). GAFQUAT 734 is a medium-molecular-weight product (ca. 100,000).GAFQUAT 755N has an average molecular weight of 1,000,000. Polyquat-emium-11 adsorbs on the surface of hair from aqueous solution to give a moreuniform and thicker layer than any other commercially offered cationic poly-electrolyte—a property which renders it especially useful as a conditioner ora palliative for damaged hair, as a preventive measure, and for simultaneoussetting and conditioning benefits (20). Scanning electron microscopy (SEM)has been used to show substantivity to hair (21). Polyquaternium-11 is an additive for improved skin feel in shaving prod-ucts, skin creams and lotions, deodorants and antiperspirants, and liquid andbar soaps. c. Polyquatemium 28 (GAFQUAT HslOO). Polyquatemium 28 is the co-polymer of PVP and methaciylamidopropyl trimethylammonium chloride (18).

262 IdsonCationic nature gives substantivity to hair and skin, providing conditioning andmanageability. Buildup with continued use is a drawback. Polyquaternium 28 (and) dimethicone (PVP 5-10, GAFQUAT HSI, ISP)is a silicone encapsulate using a shell/core structure. These products combinethe benefits of film-forming polymers and dimethicone, while minimizing thedrawbacks associated with the greasy feel and buildup noted with silicones. d. Vmylcaprolactam (VCL)/PVP/DMAEMA Terpolymer (GAFFIX VC- 713-ISP). The VCL imparts film-fixative characteristics with reduced moisturesensitivity, and the DMAEMA confers cationicity, enhancing the substantivityto hair. The principal advantage of this terpolymer is the ability to combineboth fixative and conditioning properties in one molecule. It is especially use-ful for gels, since it has good water solubility, excellent substantivity, and su-perior holding at high humidity and yet is easily removable by shampoos (20). e. STEPANHOLD [Stepan (22)]. STEPANHOLD is a terpolymer ofPVP/ethyl methacrylate/methacrylic acid and is said to be a good conditionerfor hair and skin.4. Polyquaternium 16Polyquaternium 16 is a copolymer of PVP/methylvinylimidazoline (MVI)(LUVIQUAT, BASF) (19). Three different comonomer ratios are available:70:30, LUVIQUAT F370; 50:50, FC 550; 5:95, FC 905. The higher the ratioof MVI, the less susceptible to atmospheric humidity and the harder the filmis. With increasing type number the polymer becomes more substantive. On acomparative basis this means a moderately strong conditioning activity for thetype 370, and an unusual intensive one for the type 905. The charge density ofthe three types has been found to have a linear correlation with the chemicalstructure. The charge density of the type 905 especially is extraordinarily high,indicating an unusual conditioning activity (23). Any combination of the threetypes of polyquaternium 16 may be applied in a single formula, which allowsthe composition of a \"tailor-made\" formulation by combining the respectivebenefits of the different polymer types.C. Dimethyl Dfallyl Ammonium Chloride (DDAC) Homopoiymer (Polyquaternium 6)MERQUATS (Calgon) (24) are a highly cationic series varying in molecularweight. Polyquaternium 6 (MERQUAT100) is the homopoiymer of dimethyldiallyl ammonium chloride. It has a weight-average molecular weight ofapproximately 100,000 and is excellently substantive to skin and hair to

Polymers as Conditioning Agents 263confer conditioning benefits. Unfortunately, it does not form good films andit has poor compatibility with anionic ingredients, owing to its very high chargedistribution. For these reasons, it is not suitable for use in a dilution-depositingshampoo. This polymer is used, however, as a shampoo preconditioner. Poly-quatemium 6, in dry-skin lotions, offers a combination of substantivity to theskin with a long-lasting, smooth feel. Polyquaternium 6 has been formulatedinto conditioners which contain amphoteric or nonionic surfactants ratherthan cationic surfactants and as palliatives for hair-straightening preparations(20). The incompatibility with anionic ingredients limits its use in shampoos,but in conditioners it contributes to detangling and improved wet and dry com-bability without a greasy feel (25).1. DDAC/Acrylamide (Polyquaternium 7)MERQUAT 550 and MERQUAT S (polyquaternium 7) are the copolymersof polyquaternium 6 with acrylamide (24). They have a lower charge densityand higher molecular weight (weight average mol. wt. = 500,000) and are mostsuitable for inclusion as an active ingredient in body-building shampoos. Polyquaternium 7 displays excellent substantivity to skin and hair, good filmforming, and good compatibility with anionic surfactants, although a specialgrade is required for ethoxylated surfactants. This polymer also displays asharp desolubilization of the polymer-surfactant complex at surfactant con-centrations below the critical micelle concentration (see Section K) and it istherefore ideally suited for use in conditioning body-building shampoos. These polymers also increase deposition of water-insoluble particles on hairduring shampooing. This offers special benefits for enhancing deposition ofzinc pyrithione in antidandruff shampoos (20), The combination of high charge density and polymeric character improveshair manageability. As with other cationic conditioners or creme rinses, theconditioning effects are more apparent when the MERQUAT formulationsare applied to hair damaged by chemical bleach or sunlight (26). MERQUAT polymers impart soft, silky feel to the skin. When applied todry skin, dilute solutions of MERQUAT 100 were found to dry rapidly, pro-viding a smooth surface and velvety texture. Skin product applications includeliquid and bar soaps/detergents, shaving creams, moisturizing or barrier creamsand lotions, bath products, and deodorants.2. DDAC/Acrylic Acid (Polyquaternium 22)MERQUAT 280 (polyquaternium 22) is the copolymer of polyquaternium 6with acrylic acid (24). It yields effective conditioning shampoos which areclaimed to be easier to comb wet or dry, softer to the touch, have more body,and less tendency to build static.

264 IdsonD. Polymethacrylamideopropyl Trimonlum ChloridePolymethacrylamidopropyl trimonium mer chloride [Polycare 133—RhonePoulenc (17)] is a highly charged cationic substantive homopolymer with goodconditioning and hold without film buildup. Because of its stability to hydroly-sis under alkaline conditions, Polycare 133 finds use as a conditioner for wavesystems as well as a functional additive in skin care products (17).E. Acrylamide/p-Methacryloxyethyltrimethyl Ammonium l\/iethosuifate (Poiyquaternium 5)Polyquaternium 5 [RETEN—Hercules (27)] is a copolymer of acrylamide andP-methacrylyloxyethyl trimethyl ammonium methosulfate, recommended as ahair and skin conditioner. There are eight RETENS, varying in molecularweight. They enhance foaming and interact with keratin to give a conditioningeffect. This polymer is claimed not to interact with anionic surfactants (20).F. Adipic Acid/Dimethyiaminoiiydroxypropyl/ Dietiiylenetriamine Copolymer [Cartaretin F-23, Sandoz (28)]On hair, the polymer gives good lubricity and ease of wet combing without thefeeling of oiliness sometimes associated with other cationic polymers. The per-formance of the polymer in conditioning shampoos, notably its substantivityto hair, is dependent on the types and concentrations of surfactants present inthe formulation. In general, increased deposition is favored by use of mixedanionic/amphoteric or nonionic surfactant systems, and higher concentrationof polymer solids.G. Vinyl Alcoliol Hydroxypropyl Amine (Poiyquaternium 19)Polyquaternium 19 [ARLATONE PQ-220, ICI (29)] is the quaternary ammo-nium salt prepared by the reaction of polyvinyl alcohol with 2,3-epoxypropyl-amine. Cationically modified resins find their chief use as substantive condi-tioning agents in hair preparations. However, a resin such as quaternium 19finds value in skin care because of its smooth emollient feel on the skin, as wellas its substantivity (30). Quaternium 19 also increases the protection affordedby sunscreen lotions.H. Quaternized Polyvinyl Octadecyi Etiier (Poiyquaternium 20)Polyquaternium 20 is a quaternized polyvinyl octadecyi ether [ARLATONEPQ-225, ICI (29)]. The superior moisture barrier properties result in resistance

Polymers as Conditioning Agents 265to water rinsing. Tests show that polyquatemium-20 augments the perform-ance of a simple quaternium by improving hair setting properties and lusterwithout excessive buildup (16).I. Quaternlzed ionenes (Polyquaterniums 2,17,18,27)The ionenes are cationic polyelectrolytes which are formed by condensationof di(tertiary amines) and dihalides via a quatemization reaction. Commer-cially available ionenes are polyquaternium 2, polyquatemium 17, polyquat-emium 18, and polyquaternium 27. Polyquaternium 2 [MIRAPOL A-I 5, Rhone Poulenc (31)] is defined aspoly[N-[3-dimethylaminopropyl]N'-[3-(ethyleneoxyethylenedimethylamino)propyl] urea dichloride) (Figure 4). In common with all cationic polymers,polyquatemium 2 may be used in products primarily designed for hair condi-tioning, such as creme rinses, or in conditioning shampoos. In either case,long-chain anion-active surfactants should be present for complex formation. Two chemically related polyquats, polyquatemium 17 and polyquaternium18, have been introduced which are variations of the older polyquatemium 2.Polyquaternium 17 [MIRAPOL AD, Rhone Poulenc (31)] is the reactionproduct of adipic acid and dimethylaminopropylamine, reacted with dichlo-roethyl ether. Polyquatemium 18 [LUVIQUAT 500, BASF (19)] substitutesazelaic acid instead of adipic acid. The products have a very similar function and are reported to improve wetand dry combability as well as flyaway. The main differences are found in aslightly better antistatic control by polyquatemium 17 and a better compati-bility with anionics of polyquatemium 18. Like most cationic polyelectrolytes,the ionenes give good conditioning properties but poor setting properties. Ac-ceptable setting in addition to conditioning can be achieved if a crosslinkedionene is used (20). It has been claimed that ionenes confer better wet and drycombing and shine on the hair than the traditionally used cetyltrimethyl am-monium bromide and do not build up on the hair with repeated application. Clear shampoos require the use of amphoteric surfactants as coupling agentsbetween polyquaterniums 17 and 18 and anionic surfactants. Appropriate

266 idsonamphoterics include imidazoline derivatives and amidobetaines. Polyquaternium 27 [MIRAPOLS 9, 95, 175, Rhone-Poulenc (31)] are block polymersformed by the reaction of polyquaterniums 2 and 17.J. Polyquaternium 8Polyquaterniuim 8 is the quaternary ammonium salt of methyl and stearyldimethylaminoethylmethacrylate quaternized with dimethylsulfate. It is a use-ful conditioner for both hair and skin.K. Cellulose Cationic PolymersIn order to replace hair body which has been lost by frequent shampooing andconditioning, formulators sought to introduce materials which would be de-posited on the hair from the shampoo during the shampooing process. Thebodying ingredient had to be dissolved or solubilized in the final product insuch a way that it could be \"triggered\" to deposit on the hair at an appropriatepoint in the washing cycle—preferably during rinsing, when soil and sebumhave already been removed. The breakthrough came with a quaternized hy-droxyethylcellulose derivative, polyquaternium 10 (20).1. Hydroxypropyl Trimethyl Ammonium Chloride Ether of Hydroxyethyi Celluiose (Polyquaternium 10)Polyquaternium 10 [UCARE Polymer JR, Amerchol (32)] may be describedas 1-hydroxypropyl trimethyl ammonium chloride ethers of hydroxyethyi cel-lulose. It is obtained by reaction of hydroxyethylcellulose with epichiorhydrinfollowed by quaternization by trimethylamine. It is a film-forming, water-soluble material which imparts good wet combing, curl retention, and man-ageability and has been shown to mend split ends. Studies employing radio-isotopes have shown that this cationic polymer is substantive to hair and isremovable by repetitive shampooing, the amount originally deposited depend-ing on the surfactant present in the shampoo. In general, while it can be for-mulated with anionic surfactants, greater deposition occurs from shampoosformulated with a mixture of nonionic and amphoteric surfactants (33). There are three different types of Polymer JR, JR 125, JR 400, and JR 30M,varying in molecular weight (32). The most commonly used product in condi-tioning shampoos, JR 125, has a number-average molecular weight of about400,000 and about 1300 cationic sites (34). In the presence of an anionic sur-factant, these cationic sites display coulombic attraction for the anionic headgroups of the surfactant. At 1:1 charge neutralization of the cationic polymer,a hydrophobic complex precipitates from solution (20). Surface-active molecules in aqueous solution undergo structural changeswhich indicate agglomeration of molecules to form aggregates. These aggre-

Polymers as Conditioning Agents 267gates are called micelles. The concentration at which the micelles begin toform is called the \"critical micelle concentration\" (CMC). In the presence of excess polymer or excess anionic surfactant, clear solu-tions are obtained. Shampooing is typically done above the CMC in order tosolubilize the sebum and oily soil. Polyquaternium 10 stays solubilized and outof the way of the cleaning during the shampooing process, but upon rinsingthe composition on the head is diluted below the CMC and the polymer-sur-factant complex is deposited on the hair (20). Presumably, this is due to thefact that above the CMC, hydrophobic interaction between the complex andfree surfactant causes solubilization of the complex. Below the CMC, however,precipitation of the complex occurs at all ratios of surfactant in excess of the1:1 molar equivalent ratio. The excess surfactant cannot solubilize the com-plex, because below the CMC, hydrophobic association of the surfactant mole-cules is not favored—the minimum free-energy state is one in which the sur-factant molecules are individually dissolved. The complex deposited from such cationic polymer/anionic surfactant sys-tems appears to be liquid crystalline, with rheology that lubricates and im-proves the ease of wet combing. Further, the complex has antistatic properties(35). Thus, these systems have the dual advantages of conferring conditioningbenefits on wet hair while enhancing the body and reducing flyaway of condi-tioned dry hair. They can help in mending split ends. In addition. Polymer 10provides an emollient effect and a smooth conditioning feel on the skin (32).The substantivity of UCARE and CATREX polymers on skin translates intoa perceptible silk smooth afterfeel, protecting the skin as well as conditioningit. Polyquaternium 10 has been included in formulations as a palliative in thio-glycollate hair-waving compositions and as an additive to traditional condi-tioners and in oil-free conditioners. Polymer JR is very substantive to hair and not easily removed. Use of highconcentrations may lead to overconditioning and excessive buildup. Studiesemploying radioisotopes have shown that this cationic polymer is substantiveto hair and is removable by repetitive shampooing, the amount originally de-posited depending on the surfactants present in the shampoo (2). Polyquaternium 10 is frequently used in shampoos, but polyquaternium 11is the preferred ingredient for conditioners (25). While structurally similar to UCARE Polymer JR, the analogous UCAREPolymer LR provides all the conditioning benefit of Polymer JR, but with lessdeposition on the hair. In general, while it can be formulated with anionicsurfactants, greater deposition occurs from shampoos formulated with a mix-ture of nonionic and amphoteric surfactants. Replacing part of the anionic detergent(s) by imidazolinium amphotericsurfactants dramatically increases the substantivity of cationic cellulose de-rivatives to hair (9). However, too much substantivity can be undesirable,

because unwanted excessive buildup may occur after repetitive shampooing,leaving hair feeling stiff and heavy. The CELQUAT-SC series of National Starch (36) (polyquaternium 10) issimilar to the UCARE series of Amerchol. CELQUAT SC 240 is a lower-vis-cosity analog of CELQUAT SC 230M. BIOCARE SA [Amerchol (32)] is acombination of bioengineered hyaluronic acid and polyquaternium 10.2, Polyquaternium 24Polyquaternium 24 [QUATRISOFT POLYMER LM-200, Amerchol (37)]also has a cellulose backbone. It is a polymeric quaternary ammonium salt ofhydroxyethylcellulose reacted with a laruyl dimethyl ammonium-substitutedepoxide (Figure 5). It can be considered a hydrophobically modified polyquat-ernium 10. QUATRISOFT forms a nontacky film that is substantive to bothhair and skin. It is substantive enough to withstand rinsings, but can create abuildup problem. This material acts not only as a conditioner but combinessynergistically to increase the product viscosity. ESCA (X-ray photoelectron spectroscopy) is a sensitive method used todetect the presence of adsorbed conditioning polymers on isolated, treatedstratum corneum membranes, and to rank them in terms of the amountadsorbed (38). According to these studies, polyquaternium 24 adsorbs morestrongly to skin membranes than polyquaternium 10 or chitosan. Polyquat-ernium 24 shows roughly equivalent deposition on both sides of the mem-brane, while polyquaternium 10 and chitosan deposit only on the inner surfaceof unwashed skin membranes. This is attributed to the presence of retainedlipids on the outer surface during contact with the aqueous polymer solution.3. Hydroxyethylcellulose/Diallyldimethyl Ammonium Chloride (Polyquaternium 4)Polyquaternium 4 [CELQUATS H-lOO, L-200, National Starch (36)] is a co-polymer of hydroxyethylcellulose and diallyldimethyl ammonium chloride.Cationic over the entire pH useful range, CELQUAT H-lOO and L-200 are

Polymers as Conditioning Agents 269Figure 6 Polyquatemium 46.substantive to anionic surfaces such as hair and skin. In conditioners, lotions,rinses, and shampoos, they significantly improve the appearance and manage-ability of hair. They give a lasting smooth, velvety feel to skin lotion and creams.They offer superior curl retention properties even in high-humidity conditions,excellent wet combing, and no buildup (25).4. Alkyl Dimonium Hydroxypropyl Oxyethyl CelluloseCRODACEL QL is the lauryl analog, QM the coco and QS the stearyl deriva-tive. Not only do the CRODACELS have conditioning properties charac-teristic of their parent polymer, they also have high substantivity acquired asa result of quatemizing, while retaining compatibility with anionic surfactants.The CRODACELS can also be used in skin care products, where they imparta long-lasting and lubricious feel to the skin (26).L. Polyquatemium 46To keep in step with the market trend toward multifunctionality, BASF (19)developed new conditioning polymers with improved properties, especially forstyling products: polyquatemium 46 (LUVIQUAT HOLD) (Figure 6). Theconditioning effect of polyquatemium 46 lies within the optimum range forstyling applications and is comparable with that of conventional polyquater-nium 11 and PVP/VA copolymer blends.M. Guar Hydroxypropyl Trimonlum ChlorideFollowing the success of polyquatemium 10, it was not surprising that anothercationic polysaccharide—a guar derivative—should emerge as a candidate forservice in dilution-deposition shampoos (39).

270 Idson Guar gum is a galactomannan with a p-l,3-linked mannan backbone towhich are attached a-D-galactopyranosyl residues as 1,6-linked single-unit sidechains. The cationic charge is placed on guar gum using the same chemistry asfor polyquatemium 10, that is, by hydroxypropylation, addition of epichloro-hydrin, followed by quaternization with a tertiary amine (20). Guar hydroxypropyltrimonium chloride (GHPTC), not unexpectedly, func-tions in an identical way to polyquatemium 10, but it has been claimed toconfer better wet combability. It has been used in conditioning and body-build-ing shampoos. High cationic substitution confers substantivity to skin to pro-vide conditioning. Because GHPTC is substantive, a protective polymer filmremains on the skin.N. Quaternized Lanolin (Quaternlum 33)Quaternium 33 [LANOQUATS, Henkel (40)] is quaternized lanolin. Theseproducts have many applications in cosmetics, particularly in the area of haircare products (17). Their compatibility with anionic surfactants makes themideal shampoo systems, where their function is to deposit on the hair and com-bat the effects of static electricity, thus helping to control flyaway and aid inthe ease of combing after shampooing (41). The properties of these quaternaries also make them useful in hair condi-tioners and rinses applied after shampooing. The toxicological properties oflanolin acid quaternaries have been shown to be lower in magnitude than thoseof other commonly used \"quats,\" and their solubility characteristics allowthem to be incorporated in virtually any type of hair rinse/conditioner formu-lation (42).O. Quaternized CHITOSAN (Polyquatemium 29)CHITOSAN is the deacetylation product of chitin which is a major componentof the exoskeletons of invertebrates. Combining CHITOSAN with pyrrolidonecarboxylic acid (PCA) forms a water-soluble substantive humectant whose CTFAname is chitosan PCA and which forms polymeric films on the hair. CHITOSAN that has been reacted with propylene glycol and quaternizedwith epichlorohydrin has the INCI (3) name of polyquatemium 29. Compat-ible with all types of surfactants and stable over the pH range from 2through 12, polyquatemium 29 exhibits excellent hair fixative properties atlow active levels.P. Quaternized ProteinsProteins and polypeptides derived from various plant and animal sources arecommon conditioning agents. Because of their similarity to the proteinaceous

Polymers as Conditioning Agents 271structure of hair and skin, they are naturally adsorbed. Once deposited, pro-teins are said to improve surfaces by attaching to the damaged sites. Also, theirsubstantivity can be enhanced through reaction with quaternized materials(8). Hydrolyzed homopolymer proteins are discussed in another chapter of thisvolume. This section is concerned only with quaternized cationic and nonca-tionic proteins. Quatemization yields derivatives which exhibit even highersubstantivity to hair, and are especially useful for selectively sorbing at damagesites. Steartrimonium, lauryl, cocoyl, and stearyl dimethylammonium hydro-lyzed animal protein are all commercially available.1. Quaternized CollagensBrooks Industries (43) markets quaternized collagens: hydroxypropyltrimo-nium gelatin (QUAT-Coll IPIO), cocodimoniumhydroxypropyl hydrolyzed col-lagen (CDMA), and steartrimonium hydroxyethyl hydrolyzed collagen (QS).IP-10 uses a low-molecular-weight trimethyl quat which shows excellent coun-terirritant properties in anionic surfactant systems. CDMA uses a fatty quatwhich has good wet combing, conditioning, and tangling effects on the hair.Croda (44) has the steardimonium analog (CROQUAT-S) and trimonium(CROQUAT Q), the coco dimonium (CROQUAT M), and the lauryl dimo-nium (CROQUAT L). Collagen is the principal structural protein in the body. However, collagenis only one source of skin protein for cosmetics. Another useful source is kera-tin in the form of horn, hair, hoofs, or feathers. Milk, silk, vegetables, and yeastare other sources of protein for cosmetics applications.2. Quaternized KeratinCocodimonium hydroxypropyl hydrolyzed keratin [CROQUAT, Croda (44);QUAT-KERATIN WKP, Brooks (43)] is derived from hydrolyzed keratinproteins obtained from wool. CROQUAT HH (Croda) is the same agent de-rived from the keratin of human hair. Containing cystine, it is recommendedfor conditioning perms and relaxer systems. With high substantivity, it can alsobe used in shampoos, conditioners, and creme rinses. Its affinity for keratinalso renders it useful in nail care products.3. Quaternized Vegetable ProteinWith the \"green movement\" leaning toward nonanimal sources, companieshave offered varied plant and vegetable-derived proteins. QUAT-VEG Q30[Brooks (43), hydroxypropyltrimonium vegetable protein] is one such exam-ple. On the hair it possesses all the known conditioning and substantivity ofthe traditional animal protein quaternaries.

272 Idson4. Quatemized Wheat ProteinHYDROTRITICUM QL, QM, and QS [Croda, alkyldimonium hydrolyzedwhole wheat protein (45)] are cationic quatemized wheat proteins which arehighly functional conditioning agents in both hair care and skin care products.HYDROTRITICUM QL is the lauiyl analog, QM the coco, and QS the steaiylderivative. By virtue of their compatibility with and substantivity from anionicsystems, they are suited for use in all types of hair care products—shampoos,conditioners, styling gels, mousses, and sprays—as well as skin care prod-ucts—liquid soaps, facial scrubs, skin conditioning creams and lotions, skincleansers, bath products, etc. Hydroxypropyltrimonium hydrolyzed wheat protein (QUAT-WHEAT QTM,Brooks) shows improved substantivity, enhanced moisture binding, static re-duction, and extra body-building effects on the hair. It may be used in hair andskin care products, e.g., shampoos, setting lotions, conditioners, and showerbath products. QUAT-WHEAT CDMA is the cocodimonium analog designedfor softening, conditioning, and manageability of hair; SDMA is the soyadi-monium derivative for cream rinse action.5. Quatemized Soy ProteinCocodimonium hydrolyzed soy protein (QUAT-SOY CDMA, Brooks) has anisoionic point over 9, indicating the cationic nature to show conditioning powerand substantivity. QUAT-SOY LDMA is lauryldimoniumhydroxypropyl hy-drolyzed soy protein, a softening and conditioning agent, insoluble on dilutionwith water.6. Hydrogenated Soyadimoniumhydroxypropyl PolyglucoseHydrogenated soyadimoniumhydroxypropyl polyglucose (BROCOSE Q,Brooks) is a hydrogenated soyabean fatty acid sugar quaternary based on apolysaccharide. BROCOSE Q can be considered to be a lipopolysaccharidewith conditioning power, substantivity, softening, and moisturizing effects onhair.Q. Substantive Conditioning HumectantsLauryl methyl gluceth-10 hydroxypropyl dimonium chloride [GLUCQUAT125, Amerchol (37)] and 6-(N-acetylamino)-4-oxahexyl-trimonium chloride(QUAMECTANT AM, Brooks) are substantive conditioning humectants. Whilenot cationic polymers as such, they are worthy of inclusion. They achieve theirsubstantive nature through quatemization which endows them with a posi-tively charged nitrogen which adsorbs to negatively charged hair and skin.They are skin moisturizers, adjusting the skin's moisture content in line withthe humidity.

Polymers as Conditioning Agents 273R. AminoslllconesSilicones offer a route to conditioning benefits without the buildup associatedwith dilution-deposition shampoos or the limpness associated with traditionalrinse conditioners. They increase the hair's luster and ease wet combing. Ap-plied to dry hair, they lubricate the fibers and ease dry combing. Several types of silicone polymers have been used in shampoos and otherhair care products. These include polydimethylsiloxane (PDMS) materials,silicone polyethers, and amine functional silicones. Silicones are treated in detail in another chapter of this volume. This chap-ter deals with aminofunctional siloxane and silicone-protein copolymers. Twoaminofunctional silicones have been assigned INCI names: amodimethiconeand trimethylsilylamodimethicone (TSA). They are polydimethylsiloxane(PDMS) polymers in which some of the methyl groups attached to the polymerchain are replaced by organic groups of amine functionality. Polar aminegroups along the siloxane chain have a profound effect on the silicone's con-ditioning properties, giving the polymer an affinity for proteinaceous surfacessuch as hair. TSA polymers are useful as conditioning agents for clear sham-poos based on a premix method of formulation (46,47). In effect, they provideconditioning while maintaining clarity, cleaning activity, and foam. Amodimethicone is recognized for its extremely robust conditioning andfor its ability to form clear products when used in high-surfactant shampoos(48,49). Amodimethicone is a useful ingredient in conditioners, gels, mousses,and permanents, but its use in shampoos has proved troublesome due to in-teractions between the cationic and the anionic surfactants, which can resultin compatibility problems. However, the amodimethicone emulsion can bemade compatible in high-surfactant-level shampoos (48). The other class of amine-functional siloxanes is the trimethylaminodimeth-icones (TSA). Studies show that TSA does not retain its conditioning proper-ties as long as amodimethicone does. TSA polymers are the silicones of choicefor durable conditioning and silky feel in clear or opaque formulas. Fine TSAemulsions provide easy-to-prepare, clear, stable silicone-containing shampoos.General Electric markets Silicone Emulsion SM 2658, whose CTFA designa-tion is amodimethicone (and) tridecth-12 (and) cetrimonium chloride. It driesto form a crosslinked polymer film which provides effective conditioning, par-ticularly for damaged hair. Although today's two-in-one conditioning shampoos are generally notclear, clarity can indeed be an important characteristic for some niche markets.For clarity with a more robust conditioning effect, a premixing step is typicallyrequired. This route to clarity depends on silicones that are \"solubilized,\" thatis, they are premixed with other ingredients to make them soluble. Use of thetrimethylsilylamodimethicone (TSA) family of silicones is the preferred route

274 IdsonTable 1 Subjective Hair Tress Evaluations (Rated 1-5; 1 = Best) Wet comb Wet feel Dry comb Dry feelFine TSA emulsion shampoo 2.5 2 1.5 1.5Blank shampoo 4 4 2.5 2for clarity, with strong conditioning and faster drying. A further approach toclarity depends on silicone-based (TSA) fine emulsions, which can be formu-lated into clear shampoos. The small, stable particles of silicone become dis-persed and stabilized by simple \"add-in\" formulating that requires no pre-mixing. An especially effective fine emulsion contains both amine-functionalsilicone and cationic surfactants. This route offers the formulator an addi-tional method for achieving an easy-to-formulate, clear and stable silicone-containing conditioning shampoo. Table 1 shows hair-tress conditioning datafor this formulation type and gives an indication of the combing and sensoryimprovements attainable. If clarity and good conditioning are requirements,but a premixing step is not desirable and an aging step is allowable, a high-sur-factant shampoo that utilizes amodimethicone emulsion in \"aged\" shampoosmay be the answer. High surfactant levels are useful in this conditioning sham-poo to counteract the viscosity-reduction effect of the amodimethicone and toattain clarity. This method requires that the shampoo be aged from one to twoweeks prior to use (49). Compared to the TSAs used to create clear products, those used in formingpearlescent or opaque shampoos have higher molecular weights and loweramine functionality; they provide TSA-like conditioning properties, yet for-mulate more like dimethicones. The result is a pearlescent or opaque formu-lation that still requires a premix step, but that can have acceptable viscositywithout the addition of water-soluble thickening polymers. DC929 cationic emulsion [Dow-Corning (50)] is an emulsion of an amine-functional polymer. In hair care products it provides substantivity by acting asa conditioning agent that dries to a film by crosslinking. It leaves a soft feel onhair and durability without buildup. It remains on the hair through at least sixshampoos (37). It has a very small particle size (~50 nm), which results in atranslucent product that enhances conditioning performance. DC929 and SM2658 enhance the performance characteristics of shampoos, rinses, and sham-poo-in hair coloring. They improve wet combing ease, luster, and resistanceto dry flyaway (50). Quaternium 80 [ABIL QUATS 3270, 3272—Goldschmidt (51)] is adiquaternary polydimethylsiloxane used in conditioning shampoos and hair

Polymers as Conditioning Agents 275rinses. The conditioning effect of ABILQUAT 3270 and ABILQUAT 3272improves combability of wet and dry hair; electrostatic charge is reduced andthe hair becomes silky, shiny, and manageable. ABILQUAT 3272, which is ofhigher molecular weight than ABILQUAT 3270, is more compatible with an-ionic surfactants than the latter. Therefore, ABILQUAT 3272 is preferred foruse in shampoos, shower and bath preparations, and liquid soaps, whereas themost important areas of application for ABILQUAT 3270 are conditioninghair rinses. In skin cleansing preparations the interaction of ABILQUAT 3270or ABILQUAT 3272 with skin proteins provides a refatting effect that impartsa smooth and supple feel to cleansed skin.1. Silicone Protein CopoiymersHydrolyzed wheat protein polysiloxane copolymer [CRODASONE W, Croda(44)] retains some properties of both protein and silicone components, assum-ing in part the film-forming and substantivity of a protein and the lubricity,gloss, and spreadability of silicone. While the conditioning properties of pro-teins can help improve the integrity of hair and skin, the esthetic qualities ofsilicones help to enhance their appearance. Phoenix Chemical (52) has developed a series of silicone-protein copoly-mers [PECOSIL (53)]. The compounds contain (a) a silicone portion of themolecule derived from a dimethicone copolyol, (b) an ionizable phosphategroup on the dimethicone copolyol, and (c) a protein portion. All are linkedin a covalent bond in one molecule. The presence of the phosphate groupmakes these materials silicone phospholipids. They have a tendenq^ to formbipolar sheets rather than micelles. The products reduce irritation and providea nonocclusive film on the hair and skin. There are two classes of PECOSIL silicone proteins: one containing a phos-phate group in the portion of the molecule that links the silicone and protein(PECOSIL SWP-83, SSP, SWPQ-40) and another that has no phosphate (PE-COSIL SW-83, SWQ-40). All except SSP have a wheat protein souce. SSP isderived from soya. The phosphate-containing materials have a tendency to actas natural phospholipids, while the phosphate-free version acts more like qua-ternary compounds (54).V. NONCATIONIC POLYMERSThe bulk of this chapter has been devoted to negatively charged (cationic)polymers. A number of high-molecular-weight neutral copolymers, as well asnatural polymers, exist whose main property is the fixation of hair by formingclear films. They are also substantive to and condition hair. National Starchand Chemical has been foremost in marketing these copolymers (36,55).

276 IdsonA. Vinyl Acetate/Crotonic Acid CopolymerThese copolymers are known as the RESYN series. Resyn 28-2930 is a copoly-mer of crotonic acid and vinyl acetate. The unneutralized resin is hard andbrittle. When neutralized by various aminohydroxy compounds, it becomesmore flexible. The neutralizer acts as an internal plasticizer. Resyn 2261 is an acrylic copolymer latex. It is a two-phase system consistingof submivroscopic particles of resin suspended in water. With the evaporationof the water, these resin particles flow together or coalesce to give a clear,water-resistant flexible film. It finds use in wave-set gels and conditioners.B. Octyi Acryiamlde-Acryiic Acld-Butylamlnoethyl Methacrylate Copolymer (AMPiHOMER)AMPHOMER is an amphoteric acrylic resin developed specifically as a hairfixative. It is carboxylated at regular intervals along its molecular chain. Theamphoteric character gives the polymer good curl retention, ease of combing,and conditioning effect.C. Sodium Polystyrene Sulfonate (FLEXAN 130—National Starch)FLEXAN 130 is a high-molecular-weight sodium polystyrene sulfonate. It issoluble in water, glycerine, and low-molecular-weight polyethylene glycols.FLEXAN can be plasticized by protein hydrolyzates, silicones, lanolins, andglycols. FLEXAN 130 is a primary active ingredient in conditioners and settinglotions with improved properties. It is a combination creme rinse conditionerwith set which need not be rinsed out of the hair after comb-out.D. Aminoethyl Acrylate Phosphate/Acrylic Acid (CATREX)Aminoethyl acrylate phosphate/acrylic acid copolymer [CATREX—NationalStarch (55)], when suitability formulated, deposits onto hair from shampoosystems to yield improved wet combing as well as conditioning effect and body.It can be left on hair to impart gloss, body, antistatic properties, and set hold.E. PEG Tallow Polyamine (Polyquart i-i—Henl(el)Polyamine derivatives (pseudo-cationic secondary amines) are also used asconditioning agents. It is claimed that their weak cationic character does notallow for buildup on the hair shaft, even with repeated applications. PEG 15tallow polyamine [Polyquart H—Henkel (40)] is compatible with both anionicand cationic surfactants, allowing for simultaneous cleansing and conditioning

Polymers as Conditioning Agents 277of hair. Its antistatic property is derived from its pseudo-cationic character. Itdoes not build up on the hair shaft even with repeated applications.F. Hyaluronic AcidHyaluronic acid (HA) is a natural polyanionic polysaccharide (glycosamino-glycan) present in the intercellular matrix of most vertebrate connectivetissues. Water-soluble complexes are formed by crosslinked HA (Hylan,Biomatrix) with polyquatemium 4,11 and polyquaternium 24 (PQ 24). Water-insoluble complexes are formed with polyquatemiums 6,10, and 7. In general,the polycation's charge density seems to be the most important factor in de-termining the solubility of its complex with Hylan. An important property of the Hylan-PQ24 complex is that it significantlyenhances the substantivity of Hylan to skin and hair. A PQ24:Hylan ratio of10:1 resulted in greatest substantivity to hair. BIOCARE SA [Amerchol (32)]is a combination of bioengineered hyaluronic acid and polyquatemium 10.Vi. CONCLUSiONThis review has attempted to trace the use of cationic and noncationic poly-mers in hair and skin conditioning. As styling trends required more chemicaland thermal treatments, such as perming, coloring, and blow-drying, condi-tioning treatments became more important. Modern conditioners are de-signed to provide one or more of the following functions: provide ease of wetand dry combing; smooth, seal, and realign damaged areas of the hair shaft;minimize porosity; impart sheen and a silken feel to the hair; provide someprotection against thermal and mechanical damage; moisturize; add volumeand body; and eliminate static electricity. Today, polymers offer the consumereasier, more convenient, and more versatile styling and grooming than at anytime in the past. If the trend toward temporary, quick-change styles continues, we can expectpolymers to continue to play a major role in hair care. This trend, however, isproducing and will probably continue to produce sophisticated products whichare targeted to perform just one function and to do that job very well (20).Advanced silicone technology can help reach these goals by offering a broadrange of potential formulating techniques and product characteristics. Skinconditioning remains a largely unexplored area. Much work remains to provecationic polymers as major softeners of dry skin and/or moisturizers.REFERENCES 1. Idson B. Polymers in skin cosmetics. Cosmet Toilet 1988; 103:63. 2. Hunting LL. Can there be cleaning and conditioning in the same product? Cosmet Toilet 1988; 103:73.

278 Idson 3. CTFA International Cosmetic Ingredient Dictionary. 4th ed. Washington, DC: Cosmetic, Toiletry, Fragrance Association. 4. Lochhead RY. Conditioning shampoos. Soap/Cosmet/Chem Spec 1992 (Oct.):42, 5. Goddard ED, Philips TS, Hannan RB. Water-soluble polymer-surfactant interac- tion—Part I. J Soc Cosmet Chem 1975; 26:461. 6. Fox C. Introduction to the formulation of shampoos. Cosmet Toilet 1988; 103:25. 7. Robbins CR. Chemical and Physical Behavior of Human Hair. 3d Ed. New York: Springer-Verlag. 8. Schueller R, Romanowski P. Conditioning agents for hair and skin. Cosmet Toilet 1995; 110:43. 9. Bass D, Recent advances in imidazolinium amphoteric surfactants. Soap Perf Cos- met 1977; 50:229.10. Idson B, Lee W. Update on hair conditioner ingredients. Cosmet Toilet 1983; 98: 41.11. Faucher JA, et al. Textile Res J 1977; 47:616.12. Smith L, Gesslein BW. Multifunctional cationics for hair and skin care applica- tions. Cosmet Toilet 1989; 104:41.13. Goddard ED, Schmitt RL. Atomic force microscopy investigation into the adsorp- tion of cationic polymers. Cosmet Toilet 1994; 109:55.14. Rieger M. Cosmetic use of natural fats and oils. Cosmet Toilet 1988; 103:59.15. Scott GV, Robbins CR, Barnhurst JD. Sorption of quaternary ammonium surfac- tants by human hair. J Soc Cosmet Chem 1969; 20:135.16. Davis RL New polymers for cosmetic products. Cosmet Toilet 1987; 102:39.17. Rhone Poulenc, Cranbury, NJ.18. Specialty Products for Personal Care. Bulletin, International Specialty Products, Wayne NJ.19. BASF Corp., Parisippany, NJ.20. Lochhead R. History of polymers in hair care (1940-present). Cosmet Toilet 1988; 103:23.21. Gafquat Quaternary Polymers for the Cosmetic Industry. ISP, Wayne, NJ.22. Stepan, Northfield IL.23. Goddard ED, Harris WC. An ESCA study of the substantivity of conditioning polymers on hair substances. J Soc Cosmet Chem 1987; 38:233.24. MERQUATS. Calgon Corp., Pittsburgh, PA.25. Hunting LL. The function of polymers in shampoos and conditioners. Cosmet Toilet 1984; 99:57.26. Sykes AR, Hammes PA. Use of merquat polymers in cosmetics. Drug Cosmet Ind 1980 (Feb.): 126.27. Hercules, Wilmington, DE.28. Cartaretin F-23. Sandoz, East Hanover, NJ.29. ICI Americas, Wilmington, DE.30. Good Housekeeping 1946; 122:119.31. MIRAPOL. Rhone Poulenc, Cranbury, NJ.32. Polymer JR for Hair Care. Booklet. Amerchol Corp., Edison, NJ.33. Cannell DW. Cosmet Toilet 1979; 94:29.

Polymers as Conditioning Agents 27934. Goddard ED, Hannan RB. Cationic polymer/anionic surface interactions. J Col- loid Interface Sci 1976; 55:73.35. Patel CV. Antistatic properties of some cationic polymers used in hair care prod- ucts. Int J Cosmet Sci 1983; 5:181.36. Cationic Cellulosic Polymers. National Starch and Chemical, Bridgewater, NJ.37. Amerchol Corp., Edison, NJ.38. Goddard ED, Harris WC. Adsorption of polymers and lipids on stratum corneum membranes as measured by ESCA. J Soc Cosmet Chem 1987; 38:295.39. Wilkinson JB, et al., eds. Harry's Cosmetology. 7th ed. New York: Chemical Pub- lishing Co., 1982.40. Henkel, Ambler, PA.41. Schlossman M. Quaternized lanolins in cosmetics. Soap Cosmet Chem Spec 1976; 52:10.42. McCarthy JP, Laryea JM. Effects of the use of lanolin acid quaternary in hair conditioning preparations. Cosmet Toilet 1979; 94:90.43. Brooks Industries, S. Plainfield, NJ.44. Croda, Parsippany, NJ.45. HYDROTRICUM. Croda, Parsippany, NJ.46. Kohl G, Tassoff J, Chandra O. Conditioning Shampoos Containing Amine Func- tional Polydiorganosilicone. U.S. Patent 4,559,227.47. DiSapio A, Fridd P. Silicone: use of substantive properties on skin and hair. Int J Cosmet Sci 1988; 10:75.48. Halloran D. Silicones in shampoos. HAPPI1991 (Nov.):60.49. Halloran DJ. Silicone selection guide for conditioning shampoos. Soap Cosmet Chem Spec 1992 (Mar.):24.50. DC 929 Cationic Emulsion. Dow Corning, Midland, MI.51. Goldschmidt, Hopewell, VA.52. Phoenix Chem., Somerville, NJ.53. Imperante J. O'Lenick AJ, Hammon J. Silicone-protein copolymers. Soap Cosmet Chem Spec 1994 (Oct.):32.54. O'Lenick AJ, Parkinson JK. Silicone quaternary compounds. Cosmet Toilet 1994; 109:85.55. CATREX, National Starch, Bridgewater, NJ.

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12Formulating Conditioning Productsfor Hair and SkinMort WestmanWestman Associates, Inc., Oak Brook, IllinoisI. INTRODUCTIONThis chapter is intended to provide the uninitiated chemist with a strategy forthe formulation and development of products designed to condition hair orskin. This is done with the belief that a good strategic understanding of productdevelopment will continue to be applicable and of valuable service while spe-cific formulation, or ingredient-based, approaches commonly become obso-lete or outmoded. It is not unusual for formulation technology to be replaced as the result ofscientific innovation or other developments, such as regulatory requirementsand commercial activities. An unfortunate but common example of the lattercan be found when competitors seek to adopt or emulate the formulationapproach employed by a commercially successful product. This too often re-sults in the replication of a formula with limited technical and functional meritbut one whose consumer acceptance is based on such unrelated considerationsas clever market position and appealing advertising. With these considerationsin mind, a diligent attempt has been made to augment the presentation oftechnical information with discussion of consumer, market, and corporateperceptions and requirements.A. History/BackgroundPeriodically, there have been important technical innovations in the formula-tion of hair and skin conditioners that have created new quantum levels of 281

282 Westmanfunctionality. Predictably, they have spawned an increase of related patentactivity and the adoption of similar formulation approaches by competitivemanufacturers. An example related to hair product technology (where trueinnovation has been uncommon) is the development of the first anionic-basedshampoo containing a cationic polymer during the late 1970s (1). The impor-tance of this technology was made evident both through the numer of relatedpatents granted to competitive manufacturers during the next few years andthe number of shampoos employing similar technology introduced during thattime period. The next innovation of similar importance to shampoo technol-ogy did not occur until the 1980s, when Procter and Gamble developed aneffective means to reap the conditioning potential of silicone in a shampoosystem (2). Once again, this development stimulated related competitive pat-ent activity and formula emulation. Skin care has produced many more true technical innovations. This is logi-cal when one recognizes that skin is a highly functional, living organ capableof undergoing physiological changes (i.e., improvement). (This is to be con-trasted with hair, which is not living and therefore is incapable of undergoingphysiologically induced improvement.) During recent years the use of alpha-hydroxy acids has created a new technical \"focal point\" (3) for skin careformulations. Focal points of similar technical importance include the use ofsuch ingredients as Retin A (4), liposomes (5), and biomimetic lipids such asceramides (6). It is likely that future developments in skin biochemistry willspur further formula innovations.B. Common Conditioning IngredientsAs discussed throughout this work, several classes of conditioning agents arecommonly used for both hair and skin. Each class has its own unique benefitsand formulating challenges. The reader should refer to specific chapters for adetailed discussion of these materials, but a few general comments are pro-vided here.1. Dimethicone and Silicone DerivativesDimethicone (polydimethylsiloxane) provides substantial conditioning effectsto both hair and skin when properly delivered in appropriate quantities. In-correctly formulated, dimethicone also has the potential to leave hair or skinfeely tacky, greasy, and prone to attracting environmental dust and debris. Theformulating challenge of delivering just the appropriate quantity of this cate-gory of materials is particularly acute for hair care products, since they aretypically rinsed after application. If the dimethicone droplets are not suffi-ciently small, or adequately suspended, they will coalesce and settle out ofthe system. If they are emulsified by surfactants, they will, predominantly, be

Formulating Conditioning Products 283carried away with the rinse water and be of little or no value to the hair. Procterand Gamble researchers found a solution to this problem by suspending dis-crete dimethicone droplets with the aid of a natural gum. In addition to dimethicone, the formulator should be familiar with the othersilicones and silicone derivatives. Some may be selected for their excellentperformance in specific areas of conditioning (e.g., phenyltrimethicone im-parts excellent shine), while others may be selected for their compatibility withcertain chemical systems (see Chapter 9 for a review of these materials).2. Esters and OilsThe conditioning agents included in the broad category of esters and oils gen-erally rely on their ability to smooth hair and skin with a lubricating film. Oneproblem associated with the use of these materials is that, similar to silicones,they may leave behind an objectionable residue. Another is that they are notparticularly substantive to hair or skin and therefore they are most effectivewhen delivered from a leave-on product.3. PetrolatumPetrolatum is a highly effective skin moisturizing agent but is of limited utilitydue to its poor esthetic properties—primarily greasiness and tackiness, Whileit has traditionally been held to function as an occlusive agent, serving to retainthe moisture in skin, this specific mechanism (not its functionality) has comeunder recent challenge. With the exception of its ability to impart shine, pet-rolatum's potential conditioning benefits to hair are limited primarily to thoseassociated with grooming (i.e., imparting manageability and retaining a coif-fiure). Here too, the challenge is to reap these benefits while minimizing tacki-ness or heavy feeling.4. ProteinsProteinaceous materials are purported to have restorative properties to hairand skin. Readily discernable conditioning benefits can be achieved on hair byemploying quaternized derivatives, while extremely pure forms of collagenhave been employed medically for such purposes as reducing wrinkles andassisting wound healing. The protein-related claims made for cosmetic prod-ucts have held great consumer appeal for a considerable period of time, andwhile it is likely that the preferred origin of these materials will change fromanimal to vegetable, there is no reason to conclude that this appeal will dwindlein the near future. When formulating with proteins, the chemist should bealert to potential stability issues such as discoloration, off-odor, and microbialcontamination.

284 Westman5. PolymersPolymers can be very useful of imparting slip and smooth feel to both hair andskin. Cationic polymers are particularly effective for these applications be-cause of their enhanced substantivity. This increased substantivity is essentialto typical rinse-off hair conditioning applications, where cationic polymersprovide dramatic improvement of wet comb and can minimize the \"limpening\"effect typical of cationic conditioning materials. Products containing these ma-terials must, however, be carefully formulated to avoid causing \"buildup\" orcreating the perception of dirtiness.6. Quaternary Ammonium Salts\"Quats\" are the workhorse of hair conditioning formulations. They impartexcellent softness, manageability, excellent combing properties, and essential-ly eliminate flyaway, but (at injudicious concentrations) can be irritating toskin and the eyes. Overuse on hair can also result in limpening, greasy feeling,and the real—or perceived—need for more frequent cleansing.7. HumectantsHumectants, usually polyols, are staples of skin conditioning formulations.Classically, these materials are perceived as attracting moisture from the en-vironment and making it available to the substrate (presumably skin) withwhich they are in close proximity. Contrary to the lay concept of hair moisturi-zation, this would not be of benefit to styled hair, since it would, in most cases,result in limpness, the emergence of undesirable curls, and frizziness (i.e., theprotrusion of damaged areas of hair strands from the aggregate surface).li. GENERAL FORMULATION STRATEGIESBefore focusing on considerations related directly to formulation, it is impera-tive that the chemist gain working knowledge of the structure, properties, andcommon problems associated with the intended substrate (i.e., skin or hair)and the ability to determine the impact of formulations on these substrates(i.e., performance testing). Discussions of these areas are considered beyondthe scope of this chapter but may be readily found in technical texts and lit-erature. Chapters 2 and 3 include excellent references on these topics. When formulating conditioning products for hair or skin, the chemist is urgedto impart long-term (or cumulative) improvement in addition to the normallyexpected immediate corrective benefits. Such long-term benefits may be achievedby providing a means of protection from future damage, or simply by repetitiveapplication (i.e., cumulative therapy). Both approaches require excellent for-mulation skills and thorough understanding of the underlying problem(s).

Formulating Conditioning Products 285 Successful execution may, in some cases, require the ability to integrate aformula within a formula. A product example pertaining to both skin and haircare can be found in formulations intended to moisturize. Here current symp-toms (e.g., rough, brittle/inflexible, dull, split/fissured skin or hair) should becorrected while striving for long-term elimination/improvement of the under-lying problem. For hair this could mean the inclusion of lubricants and antis-tatic agents to minimize the damage incurred while styling. For skin this couldtranslate into providing effective moisturization therapy combined with pro-tection from harsh detergents and the environment (notably UV radiation).[The term \"moisturize\" is not employed literally in relation to the conditioningof hair, since the majority of moisture is of transient presence and of littlebenefit (and most often of detriment) to hair's appearance or condition.Instead, moisturization is treated as the correction of those maladies associ-ated with dryness, including roughness, brittleness, dullness, and poor manage-ability.] Before beginning the actual formulation process, the accomplished formu-lator weighs the impact of a myriad of direct and ancillary factors. It is impor-tant for the chemist to realize that certain product development \"demons\" willbe encountered during the formulation process. These demons, some of whichare unique to a given project, are technical issues which must be overcome toensure project success. It is wise to anticipate as many of these issues as pos-sible, because for every one problem that can be envisioned there are surelytwo or three lurking unseen, in the wings, waiting to spring at the most inop-portune time. To this end, it may be helpful to draft a list of the ideal propertiesdesired of the product to be formulated. The current state of the art will notpermit development of the ideal product without significant compromise, butreview of these attributes may help the chemist anticipate obstacles that willbe encountered during the formulation process. For example, take the case of a project intended to result in the develop-ment of the ideal hair conditioner. The properties of such a product are sum-marized in Exhibit 1. A similar list of ideal properties can be prepared forwhatever product is being developed. It is important to consider these a start-ing point and to understand that there will be unavoidable limitations prevent-ing many of these attributes from being achieved without compromise.111. THE FORMULATING PROCESSA. Product ProfileIn most cases the formulator is a member of a multidisciplinary team within astructured organization. In order for the team to be successful, each membermust deliver a specific, predictable benefit. If the overall plan is well conceived

286 WestmanExhibit 1 Properties of the Ideal Hair ConditionerOne version for ail types of hair (Remember, the ideal conditioner is being described.)Visuai appearance, texture, and fragrance that are supportive of product posi- tioning and of functionai benefitsRelative ease of dispensing from packaging, tempered by the need for flow properties to support perceived functionality (e.g., the perception of a formula being \"rich in conditioners\" would not be supported by water- like dispensing)Ease of distribution throughout the hair, with \"hand feel\" consistent with product positioning and anticipated end benefits (e.g., it probably would be in error for a therapeutic conditioner to have a thin, runny hand feel)No eye/skin irritation and will not induce allergic responseEase of water rinsingWet feel varying from smooth to slippery, consistent with degree of conditioning requiredWet and dry conditioning attributes achieved without the slightest feeling of weighing down hair, without negatively impacting desired properties (e.g., body and appearance of volume, but will vary with product positioning)Absolute ease of wet comb, dry comb, and manageability during stylingInstant dryingNo flyawayDry feel consistent with positioningFlexibility, resiliency, and freedom of movement (consistent with positioning)SHINE; SHINE; SHINEand the various team members are competent, when combined these benefitswill result in a commercially successful product. In order for the formulator to deliver a specific and predictable benefit, heor she must have a clear understanding of what is expected of the formulationfrom the very onset of the program. These expectations are most effectivelyestablished and ratified in a standardized format, which can be routinely em-ployed. One approach involves creating a product profile. At minimum, thisproduct profile must include details of desired physical attributes, esthetic

Formulating Conditioning Products 287properties, functional benefits, and cost parameters. Where possible, individ-ual competitive (or internal) products should be cited as reference standards(or controls). It is also imperative that other important but less obvious infor-mation and requirements be included. At a minimum, the profile should in-clude the following considerations: Composition and design of packaging (both container and closure). Desired advertising/marketing claims. These may be formula or ingredient related (e.g., \"pH balanced,\" \"98% biodegradable,\" or \"contains vita- mins, . . . protein,... sea kelp\") or performance oriented (e.g., \"leaves hair cleaner longer,\" \"moisturizes better than the leading brand\"). \"Performance demonstrations,\" required for advertising or sales materials. Perhaps most important, the method and measure by which successful for-mulation is to be determined (i.e., criteria for successful completion) shouldalso be clearly described in the product profile. This is of paramount impor-tance to efficient project execution. An example of a product profile designedfor hair care products is provided in Exhibit 2. The product profile is typically provided as a formal document preparedwith multidisciplinary input (certainly including that of R&D) and ratified atappropriate levels of management. (Ideally, ratification should be docu-mented at all levels of the organization that will eventually be given the op-portunity to evaluate, or comment upon, formula performance or estheticproperties.) While the product profile is intended to establish a complete anddefinitive plan, at times it is prudent to adopt major change during its execu-tion. Such occasions should be prompted by response to market and/or tech-nological changes, not individual fancy or lack of forethought. Clearly, thecapable and enlightened formulator will demonstrate both the ability to exe-cute a well-thought-out plan and the flexibility to rapidly accept and respondto its modification. At times this process may require the chemist to set aside the burning desireto demonstrate technical virtuosity in favor of compliance with what may ap-pear to be a mundane product description. Consolation for such magnanimouscompromise can easily be found in the recognition that extremely difficulttechnical challenges are frequently cloaked in what appear to be extremelypedestrian assignments. In other words, it may be more difficult to formulatean easily manufacturable, inexpensive shampoo for daily use than its luxuri-ously high-lathering \"department store\" counterpart.B. Technical Evaluation and ReviewArmed with a well-crafted product profile, the formulator can truly begin theformulation process. Presuming that the targeted formulation can be achieved

288 WestmanExhibit 2 New Product Description—Hair ProductsProject Identificationi: Date:General Product Categorv:Form Prepared by:1. AESTHETICS: A. Appearanceij 1. Comparaltive Standard{s):2. Color/Hue:3. Intensity: Pale Liqht Moderate Dark4. Clarity: Clear Translucent Opaque5. Visual Effects: Pearllzed Other6. OtherB. Consistencyr.1. Compara!tive Standard (s):2. Description of Flow Characteristics (choose one):a. Water-lil<e f. Nonflowable Gelb. Very flowable, but not 9' Nonflowable water thin Cremec. Flowable, slow pouring h. Nonflowable Pasted. Barely flowable, thick i. Nonflowable Waxe. Flowable only after J. Other (describe) squeezing, shaking packagePERFORMANCE/FUNCTIONALITYA. Foam Properties:1. Comparative Standard:2. Volume: None Slight IVloderate Copious {continued)

Formulating Conditioning Products 289Extiibit 2 Continued3, Feei; Tliicl</Ricli witli Lubricious Fiim Thicl</RicliIVIoderate Thin or Describe:4. Otiier (describe):Cleansing Properties:1. Comparative Standard:2. Degree of Cleansing: Deep Moderate Everyday IVIild3. Feel of Hair After Rinsing; Scale: 0 (squeaky clean) to 10 (conditioned film)Enter number based on above Scale: I I 4. Other (describe):C. Conditioning Properties:1, Comparative Standard:2. Degree of Conditioning: Deep Normal Everyday Light3. Other (describe):Styling Properties:1. Comparative Standard:2. Drying Rate: Immediate Rapid Slow3. Hold Level: Ultra Extra Normal Light4. Other (describe):Application Characteristics (feel, visual clues):Describe, refer to existing products if applicable:F. Other Performance Characteristics: Describe, refer to existing products if applicable: (continued)

290 WestmanExhibit 2 ContinuedIII. TOTAL COST OF ALL FORMULA INGREDIENTS (excludes compounding, filling, packaging, etc.):A. Maximum cost (e.g., $0,475/16 fl.oz. product):B. Line or individual SKU limitations:C. Other:IV. CLAIMS:A. Ingredient Based Claims:Note Claims for: a. The presence of specific ingredients or type of ingredients (i.e., Formula contains INGREDIENT XYZ). b. The performance benefit that is to result (only when applicable). a. Ingredient/Ingredient Type b. Resultant Performance Benefit1.2.3.4.Performance Based Claims:1.2.3. .4.Competitive Product Based Claims:(Describe claim and specific competitive product(s)/product version(s).)1.2.3.4. (continued)

Formulating Conditioning Products 291Exhibit 2 ContinuedOther Claims:1.2.Demonstrations:1.2.V. CRITERIA FOR SUCCESSFUL COMPLETION/TEST REQUIREMENTS:This section should describe, in as definitive terms as possibie, the type oftesting that will be required and the results that must be achieved in orderfor the formulation to successfully achieve the requirements of this project. Required Testing & Results for Successful Test Design Completion1.2.4.VI. PACKAGING A. Primary Container:1. Form: Non-Aerosol Aerosol Comment;2. Size/Capacity (based on net content): fl.oz. or wt.oz.3. Tvoe (non aerosol): Bottle Jar Pouch Other4. IVIaterial of Construction (incl. type of plastic):5. Supplier & IVIodel, if selected:6. Piamented? Yes (Describe ) No7. Other (Specify) {continued)

292 WestmanExhibit 2 Continued ) ) B. Closure: 1. Material of Construction/Resin type: 2. Dispensing Closure? Yes (Describe No 3. Pigmented? Yes (Describe No 4. Supplier &iVlodei, if selected: 5. Other (Specify)VII. ADDITIONAL COMMENTS/CONSIDERATIONS:within the current realm of technology, the first step toward this end is tocollect and evaluate information regarding the functionality and safety ofavailable raw materials. This will serve to help determine an appropriate start-ing point for formulation efforts. Such information is available from a varietyof sources. The veteran chemist has the distinct advantage of having years of experi-ence on which to rely. However, in certain instances, even the veteran may beworking in an unfamiliar area. In these cases chemists of all experience levelsmust turn to other sources for their direction. Seeking the advice of colleagueswithin a company, or sphere of acquaintances, can be helpful. One can, andshould, draw upon the experience of peers whenever possible—^perhaps a simi-lar project was explored in the past and a co-worker's efforts may be beneficialto your project. In addition, it is critical that formulators know where to lookfor additional technical guidance. Many sources of such technical informationare available.

Formulating Conditioning Products 2931. Scientific JournalsOf key value is the Journal of the Society of Cosmetic Chemists and its interna-tional counterpart, the IFSCC Journal. These publications provide cutting-edge discourse by some of the leading researchers in the field. Unfortunately,they are available on a relatively infrequent basis—however, back issues canbe very helpful if they are accessible. Other journals that may be of interest tocosmetic formulators, such as The Lancet, are available from the AmericanChemical Society.2. Technical LiteratureNumerous reference works are available to the formulator; two of the bestknown are the Chemistry and Manufacture of Cosmetics, by Maison G. deNavarre (Continental Press), and Cosmetics Science and Technology, by Bal-sam and Sagarin (Wiley-Interscience). The advantage of such texts is that theyare very thorough and often combine a discussion of cosmetic theory withpractical formula information. The disadvantage is that they are publishedinfrequently and may not contain the most current information.3. Trade PublicationsSeveral monthly trade periodicals are available; these are extremely up todate and often focus on issues of specific interest to the formulator. Theyalso provide information on new product releases and trends in the market-place.4. Wendor PublicationsMost major suppliers of cosmetic raw materials make available lists of sug-gested formulations. Many vendors also provide technical support throughtheir applications laboratories. These resources are not to be overlooked.5. Patent LiteraturePatent searches can reveal a wealth of information related to specific raw ma-terials and formulation approaches. In addition to providing information onhow others have formulated similar products, they may also help ensure thatyour work does not infringe upon existing patents.6. Internet SourcesRecent advances in on-line information has brought powerful research tech-niques into the hands of every chemist with a computer and a modem. Manyvendors maintain World Wide Web sites where the formulator can learn more

294 Westmanabout the raw materials they are using. Several excellent articles have beenwritten about cosmetic science resources on the Web (7). Regardless of the sources employed to gather information, this initial researchphase is helpful in two ways. First, fundamental research provides informationabout chemical mechanisms and processes, essential to the development ofproducts based on novel or innovative technology. Second, such research canhelp establish a \"master list\" of interesting raw materials and potential startingformulations. This list must be pared down to eliminate raw materials which maybe unacceptable due to a variety of factors. For example, certain raw materialsmay be overly expensive, or they may be too difficult to handle to allow reasonablemanufacturing, or their use may be prohibited by regulatory statutes. Ideally, one would choose the most effective ingredients available withoutconsideration of cost. In reality, however, cost considerations may be key tothe product's successful commercialization and hence affect formula develop-ment. If one were to use only the most expensive raw materials in unrestrictedconcentrations, it is likely that project budget constraints would be exceeded.This is to be contrasted with the prospect of being unable to meet anticipatedperformance or esthetic goals due to adherence to unrealistic cost parameters.(Fortunately in this regard, expensive ingredients are often functional at verylow levels. For example, fragrance is often the most expensive ingredient em-ployed in a cosmetic formulation, but it is generally used at a relatively lowlevel.) Here, it is critically important for the formulator to advise R&D man-agement and Marketing if significant formula improvements can be achievedwith the relaxation of cost constraints. The manufacturing requirements of a given prototypical formula must beconsidered during the early steps of the formulation process, even though ac-tual commercialization may be months (perhaps years) away. To this end, it ishelpful for the cosmetic chemist to be familiar with typical compounding,processing, and filling equipment and the specific capabilities of the intendedmanufacturing facility. Ideally, prototypes should be designed for ready manu-facture in this facility; however should this not be the case, special require-ments must be well (i.e., \"loudly\" and promptly) communicated and plannedfor as early as possible. This will allow time for the purchase of equipment, orthe evaluation of alternative manufacturing facilities or, of course, the consid-eration of an alternative formulation approach. Regulatory factors may also affect the formulation process—even whenconsidering products intended to impart conditioning. Such considerationsmay be of great importance to such over-the-counter products as intensive skinmoisturizers or, perhaps, an antidandruff conditioner. The knowledgeable for-mulator should strive for an awareness of current and impending regulationswhich might affect cosmetic products, particularly those related to the productcategory in which he or she is involved.

Formulating Conditioning Products 295C. Prototype Preparation and TestingThe next step in the formulating process is to use the accumulated informationto prepare candidate prototypes. The primary functional objectives desired ofthe final product and the options for achieving these should be carefully con-sidered before initiating actual formulation. Furthermore, it is recommendedthe formulation be built on careful determination of the ability of candidateprimary active ingredient(s) to deliver the necessary functionality. Wheneverfeasible, this should be determined on a primary basis before beginning actualformulation. For example, before formulating a hair conditioner which fo-cuses on detangling, it is recommended that the ability to ease wet comb of2% solutions of candidate active materials (presumably quaternary ammo-nium compounds or amine oxides, with solubilizer if needed) be evaluated onlaboratory tresses. At this point, preliminary ingredient selection should also have been guidedby careful examination of basic toxicological test data (generally, primary skinirritation, eye safety, and LDso or some other measure of ingestive toxicity).For formulations built on conventional ingredients, the formulator should alsoconsider prior usage of the candidate ingredients and ingredient combina-tions. Some degree of confidence can be gained through knowledge that thegiven ingredients have previously been employed in similar products/chemicalsystems at similar concentrations, but this should not be taken as a guaranteeof safety. Exceptions exist, and additional medical safety testing of the finishedproducts may be required (8-10). In any event, become very familiar with yourcompany's policies regarding such safety testing, and gain expert input duringthe early stages of the project. Once a suitable starting point for prototype development has been estab-lished, the chemist can prepare small-scale batches. Several excellent refer-ences discuss the issues associated with laboratory batching of cosmetic prod-ucts (11,12). These developmental batches should be subjected to preliminaryevaluations to ensure that they are reasonably functional and stable. (Presum-ably, considerations related to the \"safety for use\" of the prototypes were wellinvestigated prior to the addition of chemicals to a beaker.) Depending on theconditioning requirements of the product, such preliminary performanceevaluation may, for a hair product, be limited to laboratory tress testing andcursory salon evaluation, and to confirmation of esthetic properties for a skintreatment product. Further evaluation (e.g., consumer and/or clinical testing)can take place later in the program. Similar to conducting preliminary performance evaluations, representativesamples should be stored at elevated temperatures (typically at temperaturesin the range of 37°C and/or 40''C and/or 45°^ to ensure that primary proto-types are free from gross stability defects. Based on feedback from these pre-

296 Westmanliminary tests, the prototype can be modified until the formulator is reasonablyconfident the formula is adequately robust to merit further consideration. Sincethe inherent design of this type of testing is time dependent, it is recommendedthat promising prototypes be routinely placed in the oven in order to minimizethe possibility of late disappointments. Should formulations fail in this early roundof testing, the chemist may have to pursue alternative strategies. Accordingly,it is advantageous to pursue multiple formulation strategies concurrently. Once the \"best\" formula/formulas has/have been selected, more exhaustivetesting can be conducted. At this point, thorough performance testing shouldbe done to confirm that the product meets the requirements established in theproduct profile. These evaluations may include instrumental evaluations, tresstesting, and salon studies for hair conditioning products. Skin conditioningproducts may require more extensive (and costly) clinical studies. Chapters 13and 14 focus specifically on test methodologies for these respective areas. Given the availability of adequate resources and methodology, it is advis-able for performance-related parameters to be evaluated initially under themost controlled conditions and with the procedure/instrumentation that willprovide the most precise results. For hair products, this could mean testingfirst with a Diastron, Instron, or Goniometer (or, lacking their availability,conduct laboratory tress testing) under controlled environmental conditions,with carefully controlled application amounts and procedures, and employingrelatively uniform samples of hair. Such testing will reap the most precise andreproducible results and reveal the presence or absence of even the slightestdegree of functional improvement. If you don't have it here, you don't have it.It is pointless, wasteful, and potentially misleading to proceed to a less exactlevel of testing, such as that conducted in a salon or clinical setting or throughconsumer testing, without first determining if the targeted benefit can be de-tected under precise laboratory conditions. On the other hand, it would be naive to limit testing to that conducted undercontrolled conditions, because that does not necessarily reflect reality. Forexample, the degree of improvement observed in the laboratory may not beperceivable under conditions of consumer use—and abuse. Also, controlledtesting isolates measurement to one phenomenon at a time, while the con-sumer does not. The consumer, and to some degree the salon evaluator, inte-grates and considers simultaneously clusters of performance (and esthetic)characteristics. It is therefore critical to proceed to less controlled forms oftesting such as salon testing, clinical testing, or consumer testing. Here, it isabsolutely essential that studies are properly designed and adequate replica-tions are conducted. Without such measures (which, in the case of salon test-ing, is too often the case) there is significant likelihood that results will beerroneous and misleading. Poor formulations may be adopted and excellentformulations overboked. In short, when conducted properly, such testing is rela-

Formulating Conditioning Products 297tively slow, laborious, and expensive, but very valuable. Given these consid-erations, it makes great sense to first determine, via more rapid and accuratelaboratory testing, which prototypes are worthy of such a drain of resources. Formal stability testing should be conducted under a variety of conditions.In contrast with the preliminaiy testing mentioned above, a well-designed formalstability test scheme exposes the product to a wider range of temperatures, takesinto consideration the designated packaging, even challenges the antimicro-bial preservation system of the product after heat storage. Ultimately, stabilitytesting should be performed on samples manufactured under actual productionconditions. A thorough discussion of such testing is beyond the scope of thischapter, but several references are provided for the interested reader (13,14). Once the formulator is reasonably satisfied that the formula meets the basicbenchmark requirements of the program, final evaluations can be conducted.Consumer testing, for example, is usually conducted late in the program, be-cause of its expense and relatively long time requirements. As noted above, suchtesting is very important because the consumer's integrated response to fra-grance, color, consistency, and performance characteristics cannot be pre-dicted soley through expert judgment. Successful completion of consumer test-ing is one of the most significant hurdles a potential product must overcome.D. Formula FinalizationEventually, if the product development \"demons\" have been held at bay, theformulator will arrive at a formula which meets all the criteria established atthe onset of the project. Hopefully the corporation will then proceed to com-mercialization as scheduled, but it is not uncommon for factors unrelated tothe formula to prevent this from occurring. Regardless of whether the formulais to be employed immediately or held in reserve for later use, it is helpful forthe formulator to capture key information related to the development andtesting of the product for later reference. Experience in the corporate worldhas also proven the value of maintaining this information in a concise andstandardized format, and in a single, central location that facilitates ease ofretrieval. The chemist or manager can easily refer to this important informa-tion should questions arise regarding some aspect of product development(e.g., why medical testing was or was not conducted, or why some portion ofstability testing was waived). There are specific areas of product development and testing which favorsuch documentation. These include the following: key internal tracking num-bers (e.g., formula numbers, batch numbers), criticd information related tothe testing (safety, stability, and performance) which determined the subjectformula(s) to be acceptable for commercialization, critical laboratory note-book entries, ingredient listings, relevant memos, and so forth. A sample form

298 WestmanExiilbit 3 Important Information Related to Formula CommercializationFormula: New I—I Formula i—i Product I I Revision I IProduct Name: Project Number:Related Formula Numbers: .; Within guidelines? Yes/NoA. ingredient Cost: ^_ Comments:B. Stability Testing: (Comment/explain, if no testing was required. Attach relevant memos/reports.) Formula No. Batch No. ResultsC. Microbiological Testing: (Comment, if no testing was required. Attach relevant memos/reports.)Formula No. Batch No. Study ResultsD. Process Development: (Comment, if no testing was required. Attach relevant memos/reports.)Formula No. Batch No Study Results

Formulating Conditioning Products 299Exiiibit 3 ContinuedE. Clinical or Salon Testing: (Comment, if no testing was required. Attacli relevant memos/reports.)Formula No. Batch No. Study ResultsF. iVIedicai Safety Testing: (Comment, if no testing was required. Attach relevant memos/reports.)Formula No. Batch No. Study ResultsG. (Other) Testing: (Attach relevant memos and Formula No. Batch No. reports.) Study ResultsH. Ingredient Listing (attaclied): Prepared by: DateI. General Comments: [continued)

300 WestmanExhibit 3 Continued Date:J. Approvals: Date: Date: Approved by: Date: Approved by: Approved by: Prepared by:accommodating this important information related to formula commerciali-zation is provied in Exhibit 3.REFERENCES 1. Gerstein T. Shampoo Conditioner Formulations. U.S. Patent 3,990,991, Nov 9,1976. 2. Bolich Jr, et al. Shampoo Composition Containing Non-Volatile Silicone and Xan- than Gum. U.S. Patent 4,788,006, Nov 29,1988. Gtete, et al. Shampoo Composition, U.S. Patent 4,741,855, May 3,1988. Oh, et al. Shampoo Composition. U.S. Patent 4,704,272, Nov 3,1987. 3. Van Scott E, Yu RJ. Hyperkeratinization, corneocyte cohesion and alphahydroxy- acids. J Am Dermatol 1984; 11:867-879. 4. Kligman AM, Grove GL, Hirose R, Leyden JJ. Topical tretinoin for photoaged skin. J Am Acad Dermatol 1986; 115:836. 5. Burmeister F, Bennet SE, Brooks G. Liposomes in cosmetic formulations. Cosmet Toilet 1996; 111(9):49. 6. Pauly M, Pauly G. Glycoceramides, their role in epidermal physiology and their potential efficacy in treating dry skin. Cosmet Toilet 1995; 111(8):49. 7. Klein K. The chemist's Internet. Cosmet Toilet 1996; 111(9):31. 8. Zeffren E. Preparing a cosmetic product for marketing: integrating safety testing into product development. Cosmet Toilet 1983; 98(11):48. 9. Waggoner WC. Clinical Safety and Efficacy Testing of Cosmetics, Cosmetic Sci- ence and Technology Series—Vol 8. New York: Marcel Dekker, 1990.10. Whittam JH. Cosmetic Safety, A Primer for Cosmetic Scientists, Cosmetic Science and Technology Series—^Vol 5. New York: Marcel Dekker, 1987.11. Schueller R, Romanowski P. Laboratory batching of cosmetic products. Cosmet Toilet 1994; 109(11);33.12. Oldshue J. Fluid Mixing Technology. New York: McGraw-Hill, 1983.13. The Fundamentals of Stability Testing, IFSCC Monograph. Dorset, England: Micelle Press, 1992.14. Idson B. Stability testing of emulsions. Drug Cosmet Ind 1988; 103:35-38.

13Evaluating Effects of ConditioningFormulations on HairJanusz JachowiczInternational Specialty Products, Wayne, New JerseyI. INTRODUCTIONA. General BackgroundHair conditioners are an important hair care product category with an esti-mated retail market of about $940 million in the United States alone and prob-ably a few times higher number in sales worldwide (Chain Drug Review, 1996).These products are designed to serve several functions, with the most impor-tant being to improve hair appearance, combability (detangling), and manage-ability. Some conditioning formulations can improve shine, change color, orimpart styling if appropriate ingredients are included in the formula. Also, animportant product category which has emerged during the last 20 years is thatof conditioning shampoos. One of the principal reasons conditioners are used is to prevent damage tohair by grooming and weathering, or to reduce the perceived damaging effectsof chemical treatments. Everyday grooming procedures such as washing, rub-bing, and combing primarily affect the fiber surface. This results in breakageand gradual erosion of the cuticle cells (1,2). Weathering, a combined actionof solar radiation, temperature, and humidity, results in surface damage, de-composition of protein structural components (i.e., tryptophan, cysteine), andformation of oxidation products (3). Exposure to high temperatures by the useof hot irons or hair dryers can also produce similar modifications to hair. Byfar the most severe damage is caused by chemical treatments such as bleaching, 301

302 Jachowiczdyeing, waving, and relaxing (1). These treatments result in increased surfaceroughness, oxidation of disulfide or thiol groups, and removal of hair lipids.The immediate and most obvious adverse effect of chemical treatments is anincrease in hair porosity, which provides an altered feel that is often describedas dry and raspy. Recent results of X-ray analysis suggest that chemical treat-ments can also affect crystalline, alpha-helical components of hair structure(4). Repeated use of chemical treatments may lead to even more profoundchanges, readily perceived by consumers, such as wrinkling of cuticle cells,complete stripping of cuticles, fibrillation of the cortex, and the appearance ofsplit ends.B. Chemistry of Hair ConditionersThe selection of an appropriate method for conditioner analysis, and the in-terpretation of the experimental data, is based on the understanding of themechanism of interaction for various classes of conditioning agents with hair.These include oils (pure or in the form of emulsions), cationic surfactants, andcationic polymers. The compositions may also contain a number of ancillaryagents such as fatty alcohols, nonionic or anionic polymers, surfactants, sun-screens, antioxidants, preservatives, etc. Frequently, these formulation aids caninteract with actives by forming liquid crystals, gels, lamellar phases, or com-plexes and participate in the precipitation of conditioning layers on the surfaceof hair. The function of some additives may extend well beyond the typicalfunctions of conditioning agents, as in the case of sunscreens or antioxidants.In such cases, special methods have to be used to evaluate the effectivenessof the conditioning product. This area will not be covered in this chapter. Early conditioners used by ancient Jews, Egyptians, Assyrians, Babyloni-ans, Persians, Greeks, and Romans through the Middle Ages and until the endof the nineteenth century consisted primarily of vegetable and animal oils (5).Olive, almond, and behen oils as well as softer fats of the ox, clarified beefmarrow, veal suet, and hog's lard were the materials of choice when formulat-ing products such as creams, pomades, generants, pomatums, bear greases,etc. Fragrancing was usually accomplished by the addition of essential oilsincluding oil of bergamot, lemon, roses, rosemary, lavender, etc. A recom-mended method for testing an oil, when determining its effectiveness as atreatment for hair, was to smear it on a glazed tile and expose it to air at atemperature comparable to scalp temperature for a period of two or threedays. If the oil did not become too thick or sticky (as a result of polymerizationor crosslinking), or too rancid (hydrolysis), it would pass the test and would bedeemed acceptable for hair conditioning purposes. The selection of oils for contemporary formulations is very wide and in-cludes animal-based oils such as beef tallow, lanolin, and mink oil. In addition,

Evaluating Effects of Conditioning Formulations on Hair 303vegetable-based oils have gained widespread use, such as those derived fromsoy beans, wheat germ, olive, mineral oils (i.e., paraffin oil), petrolatum, sili-cone oils, and synthetic oils (polymeric hydrocarbons, synthetic esters, or per-fluorinated ethers). The ability of various oils to perform conditioning func-tions is related to their molecular characteristics, such as surface energy,cohesive forces in surface layers, and surface shear viscosity (6,7). It also de-pends on the format of the entire hair care formulation and the presence ofother ingredients. Typically, shampoos, daily conditioners, deep conditioners,revitalizing treatments, and conditioning shampoos are formulated as oil-in-water emulsions. On the other hand, one-phase nonaqueous oil systems areused for shine-enhancing or frizz-eliminating treatments. Although oils are still in widespread use, they have been largely replacedby other specialized chemicals such as cationic surfactants and cationic poly-mers. Cationic surfactants, the most widely used ingredients of conditioningformulations, are represented by a wide variety of structures with differingperformance characteristics. The mechanism of hair conditioning by cationicsurfactants has been investigated by several researchers, with the earliest workcompleted by Robbins et al. (8) and Finkelstein et al. (9). This work helped toelucidate the surfactant structure-property relationships, the effect of hairstructure on the sorption of cationic surfactants, and the mechanism of sorp-tion from multicomponent systems containing anionic surfactants and/or poly-mers. Solution depletion methods in conjunction with kientic data analysis aswell as staining techniques employing orange II, Rubine dye, and methyleneblue were employed in these studies. At the same time, a considerable amountof experience was gained by formulation and sensory analysis of finished prod-ucts. All of this information led to the formulation of some general rules regard-ing the use of cationic surfactants in conditioners. For example, a class of satu-rated single-chain quaternary surfactants with shorter chain lengths (Cu-Cie)and characterized by faster desorption rates and thinner deposition layers, areused primarily in mild formulations for thin or normal hair. On the other hand,surfactants with longer chain lengths (Ci8-C22), characterized by their highsubstantivity to hair and thicker deposition layers, are employed in systemsdesigned for coarse and/or damaged hair. Other classes of cationic surfactantssuch as saturated multiple-chain quaternary compounds, alkylamidoamines,perfluorinated cationic surfactants, etc., may also be added to a formula toperform some special function. These functions may include triboelectriccharge control, perceived faster drying of hair, enhanced softness, \"sealing\"of damaged hair, increased moisture content, better color retention after dye-ing, increased mechanical strength, split-end mending, increased luster, andimproved rinsability or washability. These properties are normally a functionof the composition of the entire formulation and can be quantified by theselection of an appropriate measurement method.

304 Jachowfcz Another class of raw materials for hair conditioners is cationic polymers.This class of compounds tends to impart a different feel to hair than quater-nary surfactants, and their substantivity can be controlled by a selection ofmonomers, degree of quaternization, etc. They may also be deposited ontohair effectively from formulations containing a large excess of anionic or am-photeric surfactants, such as shampoos, oxidative hair dye lotions, etc. Earlywork on the interaction of hair with cationic polymers was reported by Chow(10), Woodward (11), and Goddard (12). These authors have demonstratedthat strong interactions exist between hair keratin and cationic polymers suchas polyethyleneimine, cationic cellulose, poly(dimethyldiallylammonium chlo-ride), and co(vinylpyrrolidone-methacryloxyethyltrimethylammonium meth-osulfate). A variety of different techniques were used to perform fundamentalstudies on a polymer's affinity to hair. Radio-tracer techniques with ''*C-la-beled compounds (11-13) and colloid polymer titration methods (14) wereemployed for quantitative sorption studies, while X-ray photoelectron spec-troscopy (15), electron spectroscopy for chemical analysis ESCA (16), wetta-bility (17), and electrokinetic measurements (14,15,18) were used to charac-terize the surface of hair after modification with polymers. Finally, proteins constitute an important class of conditioner raw materials.They are claimed to impart softness to the hair, increase tensile strength, addbody and gloss, enhance springiness, and improve the overall look and feel ofhair. While there is little peer-review literature to support the effect of proteinson the physicochemical properties of hair, the substantivity of polypeptides tohair keratin is well established. Quantitative sorption work has been reportedby Karjalla et al. (19), Turowski et al. (20), Mintz et al. (21), and other authors.II. REVIEW OF TESTING METHODOLOGIESA. Instrumental Techniques1. Combing AnalysisQuantitative combing measurements are frequently used to evaluate the ef-fectiveness of hair care products. The development of this technique can beattributed to Newman et al. (22), Tolgyesi et al. (23), Garcia et al. (24), andKamath et al. (25). A variation of the method, termed spatially resolved comb-ing analysis, has been recently presented by Jachowicz et al. (26). Figure 1presents a photograph of an experimental setup based on a Diastron miniaturetensile tester. In the usual procedure, a comb is passed through a hair tressand the force is measured as a function of distance. The experimental variablesinclude the dimensions of a tress, the density of combing teeth, and the typeof comb material. Most of the work reported in scientific and patent literaturerelates to hair tresses with a length in the range of 6-7 in., a weight of 1-3 g,

Evaluating Effects of Conditioning Formulations on Hair 305Figure 1 Experimental setup for performing combing measurements by employinga Diastron tensile meter.and a tress width of about 1 in. (24). The magnitude of combing forces is higherfor tresses with a higher density of hair. The combing force may also be in-creased as the distance between the teeth in the comb are decreased. Combingforces are, however, independent of the comb material, indicating that theforces are primarily due to fiber-fiber friction rather than fiber-comb friaion(27). The measurements can be performed on both dry and wet fibers. Exam-ples of dry and wet combing curves arc included in Figure 2. The wet combingcurve suggests relatively high combing forces throughout the whole tress, witha small disentanglement peak corresponding to the fiber tips. On the otherhand, dry combing traces show small forces for most of the hair tress, with theexception of a large peak at the fiber ends arising from the disentanglementof fiber tips. To illustrate the magnitude of combing forces and associatederrors. Table 1 shows typical results obtained for different types of intact anddamaged hair. The data are presented in terms of wet and dry combing works,obtained by integrating combing forces values over the tress length. Note thatthe standard deviations for wet combing range from about 15% for easy-to-comb Piedmont (unpigmented) hair to 50% for damaged hair. Similar trends,with lower errors for undamaged hair, are evident from dry combing data.

306 Jachowicz 100 150 200 250 300 350 Distance [% of initial] — wet combing — dry combingFigure 2 Wet and dry combing curves obtained by using a setup shown in Fig. 1. A basic procedure for the evaluation of the effect of a conditioning treat-ment consists of (1) measurement of the dry and wet combing characteristicsof untreated hair, (2) treatment with a conditioner followed by rinsing, (3)measurement of the dry and wet combing characteristics of treated hair, (4)shampooing, and (5) remeasurement of combing characteristics in order toascertain the removability of a treatment. This sequence of treatment, sham-pooing, and measurement can be modified to include multiple treatments forthe study of formulations such as conditioning shampoos, conditioning haircoloring products, or conditioning perms, which typically produce relativelysmall lubrication effects after a single application. The data obtained in suchTable 1 Wet and Dry Combing Works on Various Types of HairT ^ e of hair Wet combing work Diy combing work (g-cm) (g-cm)Piedmont 860 ± 130 166 ± 50Dark brown Caucasian 2179 ± 675 678 ± 171Oriental 2510 ± 890Fine brown Caucasian 3257 ± 712 —Permed 3353 ± 897 308 ± 28Bleached 4878 ± 1054Dyed 5448 ± 2447 — 309 ± 243 —

Evaluating Effects of Condttk>nlng Formulatlona on Hair 307 Untreated hair after Chemical treatment Removal of the Exposure of the wholeshampooing; combing through windows; treatment frame; rinsing with water and combing measurement. tress to conditioner measurement treatment followed by shampooing. (3) (1) rinsing; combing (2) measurement. (4)Rgure 3 A scheme of the experimental protocol for using spatially resolved combinganalysis of hair.experiments allow for an accurate assessment of the effectiveness of a condi-tioning treatment and its substantivity to hair. To obtain statistically significantdata, the measurements must be performed in replicate on several tresses. A modification of the basic procedure, termed spatially resolved combinganalysis, can be particularly useful to detect and quantify conditioning effectson hair damaged by chemical treatments and by heat or photo exposure. Adetailed description of the technique is provided in Ref. 26 with one of theexperimental protocols presented schematically in Figure 3. In this method,special frames are employed which allow the application of a treatment toselected areas of the fibers while shielding the remaining jwrtions of the tress,thereby providing internal reference sections. The combing traces of hairtreated in such a way show positive or negative peaks depending on whetherthe treatment results in an increase or a decrease in friction against the hairsurface. The damaging or conditioning effects can be further quantified bycalculating the differences in combing force or work values corresponding tothe treated areas. Figure 4 presents an example of the application of thismethod to study the effect of bleaching followed by conditioning with a cat-ionic polymer. Bleaching results in a three- to fourfold increase in combingforces as compared to untreated hair, while subsequent application of a poly-mer solution decreases the combing forces. The shape of the combing curve

before treatment — after bleaching— after bleaching + treaanent — after treatment+4 shamp.Figure 4 Wet combing traces for untreated and bleached hair obtained by followinga procedure of spatially resolved combing analysis presented in Fig. 3.after the polymer treatment, with two minima corresponding to the bleachedsections of hair, indicate that polymer-modified damaged hair is actually easierto comb than untreated hair. Moreover, adsorbed polymer cannot be removedby four shampooings, as evidenced by low combing forces and the shape ofcombing trace characterized by the minima in the bleached sections. It is note-worthy that the data presented do not point to a buildup of the analyzed poly-mer on hair. Buildup is usually analyzed by a consecutive application of thesame formulation on hair and can be quantified by the measurements of theamount or the thickness of the surface deposits. The data presented in Figure4, or results obtained in similar experiments, can be further analyzed by curvesubtraction, integration, averaging, or minima/maxima selection to provideindices characterizing the extent of conditioning, removability of conditioningagents by shampooing, and the buildup of conditioning actives.2. Tensile StrengthMechanical measurements are not frequently used to study the effect of con-ditioners on hair because it is generally assumed that the conditioner activesprimarily produce a surface modification of hair and do not affect its bulkproperties. Since mechanical modulae and viscoelastic properties of keratinare determined by the internal elements of hair structure, it is expected thatthe deposition of few milligrams per gram of a conditioning agent could not

Evaluating Effects of Conditioning Formulations on Hair 309significantly alter the mechanical properties of hair. However, this view iscontradicted by a recent report suggesting that the adsorption of polyquat-ernium-lO or guar hydroxypropyltrimonium chloride can affect the mechani-cal strength of hair (28). Measurements of hair strength can be performed bytaking standard stress-strain curves for single fibers employing a tensile tester(Instron or Diastron) (2,29). The parameters calculated from the data are thetensile strength (stress at break) or the Young's modulus, which is calculatedfrom the initial slope of the stress-strain curve. An automated tensile testingdevice for fibers, devised to shorten the processing time of a large number ofsingle fibers and to obtain statistically valid information, has also become avail-able from Diastron.3. Hair BodyHair body is an important hair attribute associated with the volume andmechanical properties of hair fiber assemblies. The importance of this hairproperty has been discussed by several authors, who stress that it is a psycho-physical attribute which can be assessed by visual or tactile perception. Thevariables affecting hair body include fiber density (hair/cm^), bending stiff-ness, hair diameter, hair configuration or shape, and fiber-fiber interactions(30-32). Several instrumental methods have been proposed to quantify hairbody, such as the ring compressibility method (33,34), radial compressibilitymethod (35), interfiber adhesion measurements (35), and tress volume meas-urements (36). In the ring compressibility method, a hair tress attached to aload cell of an Instron tensile meter is passed through compressing rings withvarious diameters and the force is measured as a function of distance. In-creased body or springiness of hair is indicated by higher compression forces.In the radial compressibility method a tress is radially compressed twice by acompression ring attached to a load cell. From this experiment several pa-rameters, including the fiber adhesion index (FAI) and AE2, can be calculatedas follows: AF = lQQ(-^2, treated ~ -^2, untreated) ^ 2 , untreated pA T _ 1 0 0 ( ^ 1 , treated ~ •^2, treated) ^1, treatedwhere £i and £2 are the energies of the first and second compressions, respec-tively, and treated or untreated refers to treated or untreated hair. The FAIgives information about the recovery of treated fibers from compression,while AE2 quantifies the effect of treatment on the energy of the second

310 Jachowiczcompression. AEi was found to be less dependent on tress preparation whichconsists of combing and fluffing than the analogously defined AEi parameter. Measurements of tress compressibility may be complemented by measure-ments of the interfiber adhesion, which can be performed by pulling a singlefiber out of a bundle and recording the forces with a microbalance. The pa-rameters characterizing hair body, AE2, interfiber adhesion, FAI, and £i werefound to correlate with the body rating of tresses by expert panels.4. Measurements of LusterThe gloss or luster of hair is an important property which can be visually as-sessed by a consumer and is also considered to be a desirable hair attribute.Several instrumental methods have been employed for quantitative charac-terization of hair luster and for the evaluation of the effect of various cosmetictreatments on hair gloss. These include goniophotometric techniques and im-age analysis. a. Goniophotometric Techniques. The use of goniophotometers is themost precise way of quantifying optical properties of hair. The foundation ofhair gloss research was laid by a series of papers by Stamiii et al. (37) whichexplored the effect of hair morphology on hair shine and gave a quantitativeand qualitative description of light-scattering curves. Goniophotometers canperform measurements of light scattered by fiber tresses (37,40) or by singlefibers (38,39) as a function of an incidence or receptor angle. In the mostfrequently employed procedure, a light source illuminates a hair sample at anincident angle and the light intensity is recorded for different receptor anglesresulting in a light-scattering curve. An example of a typical light-scatteringcurve, with light intensity as a function of the scattering angle, is given in Figure5. It consists of a primary peak due to specular reflection (for the incident angleof 45° the specular reflection should appear with the maximum at about 90°)and a secondary peak arising from light which penetrated hair and is reflectedor scattered on the internal elements of the fiber structure. In highly pig-mented fibers the intensity of the secondary peak is small. While the lightcontributing to the specular reflection is largely co-polarized (i.e., polarized inthe same direction as the incident light), the light corresponding to the secon-dary peak is significantly cross-polarized. In addition to this, the intensity (orsharpness) of the light-scattering curve can be affected by the polarization ofthe incident and reflected light. The reason for this is that the reflected s-po-larized light (light with its electronic vector perpendicular to the plane of in-cidence) is approximately five times more intense than the reflected p-polar-ized light, which, in turn, is due to the difference in reflection coefficients fors- and p-polarized incident light.

Evaluating Effects of Conditioning Formulations on Hair 311 acaitering Angle /°Figure 5 Goniophotometric curves of fibers illuminated (at an incident angle of 45°)using unpolarized white light. Data have been normalized so peak intensity corre-sponds to unity. (From Ref. 38.) A quantitative measure of luster can be calculated by the followingformula:where L is luster or shine, D is integrated diffuse reflectance, 5 is integratedspecular reflectance, and Wi% the width of a specular peak at half-height. The shape of the light-scattering curve for untreated hair, and thus theintrinsic luster of hair, depends on the state of the hair surface and the degreeof hair pigmentation. An increase in melanin content in dark-colored hairreduces the intensity of light scattered on the internal cuticle surfaces and onother internal elements of hair structure. This results in lowering the diffusereflectance and sharpening the specular peak, consequently providing an in-crease in hair luster. For damaged hair, in which the surface layers of cuticlesare jagged and uneven, the intensity of scattered light (diffuse reflectance) ishigh to the point that the incident reflection peak can appear as a broad pla-teau rather than a sharp peak. It has been demonstrated that some types ofhair treatments, including conditioning hair rinses, can increase the \"sharp-ness\" of the specular reflection and thus improve the luster of damaged hair.On the other hand, it was found that the luster of intact, undamaged hair,characterized by a well-defined and \"sharp\" specular reflection, cannot beincreased by application of conditioning rinses or conditioning shampoos, which

312 Jachowiczusually leave a light-scattering deposit on the hair surface. An increase in shinefor this kind of hair can be produced by the use of oil-based shiners or clearhairspray resins which are capable of forming a continuous film on the surfaceof the fibers. b. Image Analysis. Luster measurements can also be performed by usinga color image processor which can analyze a pattern of light reflected by anatural-hair wig on a model head (41). In this study, hair was illuminated withwhite light at an angle of 30°. The data were obtained by scanning across high-lighted and dark areas of the obtained image, and could be presented in a plotsimilar to a photogoniometric scattering curve. In addition to this, the reflectedlight could be resolved into three color signals, R, G, B (red, green, and blue)or intoL*, fl*, b* parameters. Good agreement was found between calculatedluster, defined as the ratio of the lightness in the highlight area to the lightnessin the dark area, and the rating of luster obtained by a visual inspection of hairtresses. An even better correlation was found by employing a contrast parame-ter defined aswhere Lph is luster, BH is blue light intensity, and Rd is red light intensity in thedark area. The values of this parameter were found to be consistent with thevisual ratings of luster for hair treated with hair dyes and a variety of hairgrooming products. According to this work, oil-based luster sprays, styling gels,and pomades were effective in increasing the luster of hair. In contrast to otherreports, the use of a conditioner after shampooing also resulted in an increasein specular reflection and a decrease in scattered reflection. In addition to this,the technique was found useful in substantiating the luster variations in col-ored hair, such as in blue-dyed Oriental black hair.5. Visual Evaluation of LusterThe method of subjective shine evaluation is commonly used and can provideuseful guidance for formulators. The results can be in good agreement withinstrumental methods provided the experimental setup assures uniform ori-entation of hair samples and reproducible (from sample to sample) illumina-tion conditions. The method usually employs special mounting frames whichexpose the tested tresses to artificial light illumination in such a way as toproduce highlight (specular reflection) and dark areas. For example, Reich etal. (39) reported using hair tresses mounted at the root end and stretched overthe cylinder while secured at the tip. Six tresses were mounted in a row on thetesting rack and were illuminated by four bulbs in a single row approximately10 in. above the tresses. The tresses were evaluated by 16-20 panelists, who

Evaluating Effects of Conditioning Formulations on Hair 313ranked the tresses in order of relative shine. After each evaluation, the tresspositions were interchanged to minimize any positional bias. An alternativemethod of visual evaluation was described by Maeda et al. (41), who used hairbundles attached to a model wig which were illuminated at an angle and evalu-ated by five experienced analysts. It should also be mentioned that visual evaluations and tress rankings,such as those described above, can be complemented by simple light-intensitymeasurements using a photographic spot meter (for example, selected modelsmanufactured by Minolta) to obtain a quantitative measure of gloss accordingto the formulawhere S is the intensity of the specular reflection and D is the intensity meas-ured in the background, diffuse scattering area.6. Dynamic Electrokinetic and Permeability AnalysisAlthough streaming potential analysis of fibers has been used in the textilechemistry for some time, the simuUaneous measurement of electrokineticparameters (streaming potential and conductivity) and permeability of fiberplugs is a relatively new approach to study both model conditioning activesand complete commercial formulations (18,42). A simplified scheme of aDEPA experiment is presented in Figure 6. A typical experimental protocolincludes the measurements of untreated hair, treatment with a conditioningagent, and measurements of the kinetics of sorption/desorption of ions duringrinsing with a test solution (5 x 10\"' M KCl). The streaming potential data,converted into zeta potentials by means of the Smoluchowski equation, giveinformation about the state of the fiber surface and the presence of adsorbedanionic or cationic groups. Conductivity, on the other hand, is related to thepresence of free ions in the test solution (although surface conductivity of hairmay also be a contributing factor), and its variation in the course of experimentis due to the desorption of ions into the test solution. In addition to this,changes in the flow rates (permeability) indicate variations in the volume ofthe fibers (i.e., swelling or shrinking) or deposition of surfactant or polymeron the fiber surface. The method was employed to study single- and multicomponent surfactantor polymer solutions and permitted a comparison of their ability to modify hairsurface. Quaternary ammonium surfactants, fatty amines, cationic polymers,and silicone emulsions were investigated as model systems and provided back-ground information about the behavior of various colloids (18,42). Prototypeand commercial formulations of various types were studied as 1% aqueoussolutions (42). The main criteria for performance were (1) changes in zeta

314 JachowiczFigure 6 A scheme of an apparatus for performing dynamic electrokinetic and per-meability analysis of hair plugs.potential as a result of the application of a conditioning treatment includingthose occurring during the rinsing period, (2) changes in permeability of theplug and thickness of a deposited conditioning layer, and (3) changes in plugconductivity. Typically, hair treated with conditioners containing water-sol-uble and less substantive ingredients is characterized by thinner deposits ofconditioning agents and by lower zeta potentials. Low-substantivity condition-ers may also desorb during rinsing with the test solutions, as evidenced by agradual decrease in zeta potentials and an increase in permeability. On theother hand, conditioners based on water-insoluble quats such as polymers andamino-functional silicones result in higher positive zeta potentials, thicker de-posited layers, and less variation of these parameters as a function of rinsingtime. Figure 7 presents the DEPA analysis of three commercial conditioners,

Evaluating Effects of Conditioning Formulations on Hair 315 10 20 30 40 50 TIME (min) n CONDITIONER C + CONDITIONER D • CONDITIONER E(a) TIME (min) o CONDITIONER C + CONDITIONER D • CONDITIONER E(b)Figure 7 Experimental traces obtained by using DEPA measurements, (a) Zeta po-tential, (b) flow rate, and (c) conductivity as a function of time for hair treated with 1 %solutions of conditioners C, D, and E (42). {continued)

316 Jachowicz 10 20(c)Figure 7 Continued.C, D, and E, designed for damaged/dyed, regular, and fine hair (42). The datapresented in the figures are consistent with the above-delineated criteria ofperformance. Conditioner C, based on most substantive ingredients, producedthe greatest change in zeta potential of hair and also precipitated the thickestconditioning layer. On the other hand, the use of conditioner E resulted in theleast extensive surface modification, as evidenced by a gradual decrease of zetapotentials during rinsing with the test solution and a relatively thin layer ofconditioning agents on the hair surface. Conditioner D showed behavior in-termediate between that of conditioners C and E. DEPA experiments with multiple applications of a conditioner followed byshampooing can provide information about the removability of conditionerresidues from hair and can be used for the evaluation of buildup parameters.The results of such an experiment are presented in Figure 8 as plots of zetapotential, flow rate, and conductivity as a function of time. The conditioneremployed in this study was based on substantive components such as bephenyl-trimethylammonium chloride and silicone emulsion DC 929 and resulted in asignificant modification of hair as reflected by high positive values of zeta po-tential and a thick, 3.56-)Ltm layer of the conditioning agent. Subsequent sham-pooing washed away most of the adsorbed species, lowering the zeta potentialsand reducing the thickness of the conditioning layer to 0.71 fim. The data fromthis experiment can be used to calculate the extent of removability of condi-tioning residues in a shampooing step and their buildup as a result of two

Evaluating Effects of Conditioning Formulations on Hair 317 0 5 10 15 20 25 30 35 40 45 50 55 60 65 70 75 80 85 TIME (MIN)(a)4.5- 0.71 pm 0.37 pm 4- t d%3.6- 3.58 pm 3.27 p m§ 2.B 1.5. 1- 0.5- 6 5 I'O 15 a'o 25 30 35 40 46 50 55 60 65 70 76 80 85 90 TIME (MIN)(b)Figure 8 Experimental traces obtained by using DEPA measurements, (a) Zeta po-tential, (b) flow rate, and (c) conductivity as a function of time for hair treated in asequence conditioner-shampoo-conditioner-shampoo. (continued)

318 Jachowicz TIME (MIN)(c)Figure 8 Continued.conditioner/shampoo applications. The results of such calculations based onzeta potentials are shown in Figure 8a and indicate that the buildup of condi-tioning agents for this system is small. In addition, the kinetic conductivity dataprovide rate coefficients of desorption of shampoo surfactants during rinsingwith the test solution. This parameter can probably be correated with the easeof rinsing off residual amounts of surfactants from hair, and the results pre-sented in Figure 8c suggest faster desorption rates after the second shampooapplication. Finally, DEPA can be employed to substantiate the \"sealing\" effects onhair. For example, the \"sealing\" effect produced by a microemulsion wasdemonstrated on hair colored with semipermanent dyes (48). On contact withwater, such hair exhibits increased plug conductivity resulting from a diffusionof the dyes out of the fiber structure into the test solution. A treatment of dyedhair with cationic silicone emulsions resulted in an immediate reduction inplug conductivity, suggesting that the deposited layer of silicone oil hinderedthe diffusion of the dyes and surfactants out of the fiber. Similar results werealso obtained for other cationic conditioning agents used as treatments foroxidatively dyed or bleached hair (44).

Evaluating Effects of Conditioning Formulations on Hair 3197. Wettability l\/leasurementsTactile perception of hair and its interactions with hair care formulations canfrequently be correlated with the wetting behavior of hair surface. Therefore,the wettability of hair was studied to determine relevant parameters such ascontact angles in various liquids, wettability forces, wettability as function ofsurface modification, etc. (45-50). All of these studies were carried out usingthe Wilhelmi balance method. A fundamental surface parameter calculated from wettability measure-ments is the contact angle of a liquid with the fiber surface, as defined by theYoung-Dupre equation:where and are solid-vapor, solid-liquid, and liquid-vapor inter-facial tensions and 0 is the solid-liquid contact angle.In the case of Wilheimi balance measurements, wettability W, defined asthe wetting force w per unit length of the wetted perimeter P, is given byThe apparatus for the wetting force measurements consists of an electrobal-ance and microscope stage for raising and lowering the liquid level. The devicecan measure both receding and advancing wetting forces, from which parame-ters such as wettability angles, wettability forces, work of adhesion, and wettinghysteresis can be calculated. Fiber perimeter can be estimated by determiningthe lengths of the major and the minor axes from microtomed cross sectionsof the fiber by optical microscopy, or by using a laser diffraction method. Based on fiber wettability measurements, intact hair (root section) was foundto be hydrophobic, with the advancing and receding contact angles equal to103° and 89°, respectively. The critical surface tension of intact hair was foundto be 26.8 ± 1.4 dyne/cm, with the dispersion and polar components equal to24.8 ± 2.2 and 2.6 ±1.3 dyne/cm, respectively. These data are based on themeasurements of advancing contact angles in water and methylene iodide.Weathering and chemical treatments typically make hair more hydrophilic,resulting in a decrease in contact angle and an increase in wettability forces.For weathered hair, the advancing contact angle was shown to be reduced to72°, and similar decreases were observed for bleached or permed hair.Deposition of cationic polymers and surfactants, actives frequently employedon conditioning formulations, can modify the surface characteristics ofhair. Adsorption of cationic polymers or surfactants on intact hair wasfound to produce more hydrophilic hair. For example, for hair treated with

320 Jachowiczpolyquatemium 10, advancing wettability increased from -8 ± 3 mN/m foruntreated hair to 35 ± 16 mN/m for hair with an adsorbed layer of the polymer.This technique was also shown to yield information about the distribution ofsurface deposits, the effect of temperature on the interactions between hairand surface-modifying agents, and the degree of surface coverage by adsorbedpolymers or surfactants (47,49). Multicomponent systems containing surfac-tants and polymers were also employed to simulate the performance of com-mercial formulations such as shampoos and conditioners. In the case ofshampoos, a commonly occurring phenomenon is the formation of complexesbetween anionic surfactant and cationic polymer, which were shown to pro-duce hydrophobic or hydrophilic surface deposits depending on the ratio ofpolymer/surfactant concentrations (49,50). Cationic surfactants, on the otherhand, were shown not to interact with the cationic polymers, due to chargerepulsion, but to compete with them for the adsorption sites, thus affectingtheir relative surface coverage.8. Analysis of Triboelectric Charging (Static Electricity)Triboelectric charging of hair is frequently observed, especially in low-humid-ity conditions, giving rise to studies concentrating on the mechanism of thisphenomenon. One of the earliest reports was Martin's observation of a direc-tional triboelectric effect for wool fibers (51). He reported that a fiber pulledout of a bundle by the root carried a positive charge, while a fiber pulled outby the tip carried a negative charge. Martin attributed this sign-reversal phe-nomenon to the piezoelectric effect. The directional triboelectric effect in hairwas further confirmed by Jachowicz et al. (52) while performing rubbingelectrification experiments using materials characterized by various workfunctions such as Teflon (reported work function range: 4.26-6.71 eV), alumi-num (3.38-4.25 eV), nylon (4.08-4.5 eV), polycarbonate (3.85-4.8 eV), andpoly(methyl methaciylate) (4.1-4.7 eV) as rubbing materials. It was shownthat the sign and magnitude of static charge on hair depends on both the di-rection of rubbing (root to tip or tip to root), as well as the nature of the rubbingmaterial. The instrumentation employed for these studies is presented in Figure 9. Ahair tress was mounted in clamps in such a way that it formed a smooth layerwith the fibers positioned so that the cuticle edges pointed either downwardor upward. Static charge was produced by contact between a rubbing element,in the form of a half-cylinder attached to an adjustable arm rotated by anelectrical motor, and the hair fibers. The generated tribocharge was measuredas a function of time by means of a static detector probe connected to anelectrometer. The rubbing element was exchangeable, which permitted theexamination of hair electrification by a variety of materials such as Teflon,aluminum, gold, stainless steel, nylon, etc. Charge decay measurements were

Evaluating Effects of Conditioning Formulations on Hair 321Figure 9 A scheme of an instrument to measure static charge generated by rubbinghair: (A) mechanism for changing fiber tension; (B) power supply; (C) operationalamplifiers (Analog Devices, Model 2B31J); (D) computer and A/D converter (ModelDT 2801, Data Translation, Inc.); (E) electrometer (Keithley Model 616); (F) staticdetector probe (Keithley, Model 2503); (G) motor; (1) and (7) load cell holding ele-ments; (2) and (6) load cells (Sensotronics, Model 60036); (3) clamps; (4) fiber tress;(8) adjustable arm with rubbing element; (9) mechanism for adjusting the length of thearm; (10) mechanism for positioning the static detector probe; (11) table for motor;(12) mechanism for positioning the fibers (57).performed with the same setup by following the changes in generated chargedensity as a function of time. A detailed study of triboelectric charging was performed by using severalrubbing materials and for two directions of rubbing from root to tip (rt, cuticlespointing downward) and from tip to root (tr). These data suggest that polycar-bonate and chitosan acetate are characterized by work functions very close tothat of hair (for rt and tr rubbing acting as electron acceptors and electrondonors, respectively), that poly(methyl methacrylate) has a lower work func-tion, and that the other materials tested (nylon, Teflon, stainless steel) lie abovehair in the triboelectric series. It was also demonstrated that both the kineticsand extent of tribocharge generation may be dependent on the mechanical orelectrostatic history of hair. This was ascribed to the fact that triboelectricproperties of hair surface might be influenced by its state of strain (permanentdeformation and opposite polarization of the cuticles induced by stretching orcompressing during rubbing in the rt or tr mode, respectively), or by nonequili-brium distribution of electrons. Further information about the mechanism oftriboelectric charging and fiber conductivity was derived from charge decaymeasurements. It was concluded that, at low humidity, the kinetics of chargedecay are nonexponential and the charge carriers can become trapped indefi-nitely on the hair surface, giving permanent tribocharges and resulting in aflyaway phenomenon. For example, for initial charge density of 2.09,3.62, and

322 JachowiczFigure 10 Energy diagram illustrating the effect of surface treatments on the workfunction of hair.5.09 C/cm^, the half-time of the decay was found to be infinity, 50.8 rain, and226.0 min, respectively. Tribocharging characteristics of hair can be modified by ad(b)sorbed sur-factants, polymers, complexes, silicones, acids, bases, and other materials usedin cosmetic formulations, including conditioners (53-57). The results of tri-boelectric charging of surface-modified hair fibers are summarized on the en-ergy diagram presented in Figure 10. Long-chain quaternary ammonium saltsincrease both the value of the effective work function of the fiber surface andthe fiber conductivity. Depending on the length of the alkyl group in the qua-ternary ammonium salts, the half-times for the charge decays varied in therange from 1.2 to 11.7 min. Longer-chain alkyl quats exhibit much higher abil-ity to increase conductivity than their short-alkyl-chain analogs. This might berelated to the fact that the longer-chain alkyl ammonium salts resist rinsingand consequently are deposited on the surface in much larger quantities. Theeffect of cationic polymers was not as pronounced and clearly defined as thatof quaternary alkyl salts. Adsorption of the cationic polymer poly(l,l-dimethyl-piperidinium-3,5-diallyl methylene chloride PDMPAMC or Polyquaternium6) results in a lower work function of modified fibers, with the effect of themodifying layer superimposed on the directional triboelectric effect. On theother hand, the triboelectric properties of poly(methacrylamidopropyltrimethyl

Evaluating Effects of Conditioning Formulations on Hair 323Figure 11 An instrament to measure combing forces and distribution of triboelectriccharges on hair: (1) motor; (2) discharging element; (3) comb (four teeth, 1.5 mmthick); (4) holding frame; (5) static detector probe (Keithley, Model 2503); (6) hairtress; (7) load cell (Sensotronics, Model 60036); (A) and (C) power supply (+10V,+ 15V); (B) operational amplifier (Analog Devices, Model 2B31J); (D) electrometer(Keithley, Model 616).ammonium) chloride were found to be strongly dependent on the polymerconcentration in the treatment solution (57). An even more complicated pic-ture emerged from the analysis of triboelectric charged hair modified by sili-cone oil, which showed a reversed directional triboelectric effect (the chargebecame more negative in the root-to-tip than in the tip-to-root mode of rub-bing). Silicone oils also lower the conductivity of hair reflected by very lowdecay rates, and result in a permanent charge on the surface of hair. Data werealso obtained for fibers treated with both the cationic polymer, polyquater-nium-6, and silicone oil, which illustrated an additive effect of both layers onthe kinetics of tribocharge generation (57). More real-life combing electrification experiments, correlating combingcurves with triboelectric charge distributions, can be performed by using aninstrument comprising of a load cell and a static detector probe interfaced witha computer (53,58). The instrument, presented in Figure 11, allows measure-ments of single and multiple combing characteristics, providing plots of comb-ing force or charge density as a function of position in the tress. The data canbe analyzed by comparing the charge or force distributions, or by taking anintegrated value of these parameters (average linear charged density or comb-ing work expressed in C/cm^ or G-cm, respectively) over the length of the tress.The measurements performed using insulator combs indicated that the typicalcharge distribution for clean hair fibers consists of two or three distinct peaks.

324 JachowiczThe peak corresponding to the upper section of the tress was usually the mostpronounced, and the one due to disentanglement of the fiber tips (correspond-ing to a peak in the combing curve) contributed to the total generated chargedensity to only a small extent. In the case of metal combs, the charge distribu-tions were different and paralleled more closely the combing curves in whichthe most prominent peak was generated at the fiber tips. The technique couldalso be used to study the effect of surface modification with conditioning agentson triboelectric charging. It has confirmed the results of rubbing experimentsby showing that the electrochemical surface potential gap between the comband keratin is a decisive factor in determining the magnitude and sign of thegenerated charge. Finally, a simplified analysis of triboelectric charging can be performed bymeasuring the voltage of the charged surface of hair, generated by manualcombing with a static detector probe and an electrometer (56). All such meas-urements must be carried out at controlled relative humidity in the range of25-40% RH, and the measurements have to be repeated several times on atleast two different tresses to obtain a statistically valid average of static voltage.In addition to this, to ensure the consistency and reproducibility of the data,it is advisable to examine concentration dependencies and to report the resultsin terms of static voltage relative to untreated controls. As for any kind oftriboelectric measurements, especially those involving samples modified bysurface treatments, reproducibility may be a problem, due to mass transfer,surface contamination, and surface abrasion during the sliding contact be-tween the comb and the fiber surface.9. Substantlvity Verification by Dye StainingVisual evidence of the presence of cationic conditioning agents on the surfaceof hair can be obtained by staining hair with anionic dyes such as Rubine dye(59). OH SOsNa I SOi* &^)'=^ f,.j Rubin Red dyeSince this material is no longer available commercially, similar dyes such asRed 80, Red 84, Orange II, and Orange G can be employed. The hair treat-ment procedure involves the use of 3.4 mM dye aqueous stock solutions con-taining acetic acid which are diluted 1:5 for a 1-min treatment of hair. The dyesolutions produce little change in coloration of intact hair or hair treated with

Evaluating Effects of Conditioning Formulations on Hair 325quaternary alkyl compounds with a chain length below CIO. For longer-chaincationic surfactants, the extent of hair coloration becomes very high, reach-ing reflectance values as low as 17% for C16-containing quaternary am-monium compounds. This technique can be employed to detect the pres-ence of cationics on the hair after the application of creme rinse formulationsbased on cationic surfactants or conditioning shampoos containing cationicpolymers. The staining procedure may also be employed to study the extent of surfac-tant penetration into the structure of hair. For this, cross sections of quat-treated fibers can be stained with dye solutions and examined under the mi-croscope for the rate and depth of diffusion of a quaternary compound.10. MicroscopyBoth optical and scanning electron microscopy are frequently used to assessfiber integrity and the state of the fiber surface. Major irregularities or damageto the fiber structure, detectable by microscopic methods, include split ends,fibrillation, lifting of cuticles, cuticle abrasion, excessive swelling in water, etc.(60,61). Many of these problems can be avoided by frequent use of condition-ers. This can be demonstrated by inducing frictional damage to intact andconditioner-treated hair followed by a statistical analysis of scanning electronmicroscopy (SEM) micrographs. Other aberrations of the fiber, such as splitends, can be also eliminated by the use of cationic polymers as conditioningagents. SEM, optical microscopy, and fluorescence microscopy may also beemployed to analyze the distribution of conditioner on the hair surface (2,50).B. Noninstrumentai Analysis of Hair Tresses1. Sensory AnalysisA comprehensive review of the whole process of noninstrumentai cosmeticproduct testing is given in several publications (62-65). Moskowitz (62) de-scribes a generic procedure which can be applied to the process of developmentof any cosmetic product, including hair conditioners. A number of steps arecarried out by R&D, marketing, and marketing research, including (1) conceptdevelopment (marketing), (2) product feasibility analysis (R&D), (3) concepttesting (marketing/marketing research), (4) screening of ingredients and pro-totype development (R&D), (5) instrumental analysis, noninstrumentai analysison hair tresses, (6) prototype screening (small scale by internal expert panelin R&D, salon testing), (7) larger formula optimization (R&D, marketing/marketing research), (8) final in-house optimization (R&D expert panel, smallconsumer panel), (9) product/concept test (marketing research), (10) confir-matory home-use test (marketing research), and (11) test market (marketingresearch). A detailed discussion of each element of this comprehensive

326 Jachowiczprocess, such as the organization and selection of panels, formulation of de-scriptors, and statistical data analysis, is beyond the scope of this chapter. Also,specific problems such as the segmentation of the product for various hairtypes (thin, normal, or damaged hair), or the assessment of product fragranc-ing is not covered by this chapter. In the following paragraphs the discussionis limited to three important steps in the development of a new conditioner:evaluation of a product on hair tresses by an expert panel, salon testing, andhome-use consumer testing. The reader may refer to Chapter 12 for additionaldiscussion of these steps. An important step in the evaluation of a conditioner is testing performedby a panel of experienced evaluators on hair tresses. This test is conducted tocompare various attributes of the formulation as they relate to the process ofproduct application on hair and to judge various properties of treated hair.The procedure involves the use of a standardized type of hair in the form ofhair swatches. Selection of a proper hair type is critical in the evaluation ofhair conditioners because these products have significantly different perform-ance characteristics depending on the type of hair to which they are applied.For example, a product formulated to treat damaged hair will probably beinappropriate for normal or fine hair because of excessive deposition of activeson the hair. A minimum of three swatches is usually used for each product tobe evaluated. Hair is shampooed before treatment with a standard surfactantsolution (i.e., 3% ammonium lauryl sulfate) and aspecified amount of productis applied to hair, usually 1-2 g of formulation per 2 g of hair tress. The for-mulation is worked into wet hair manually, left on the hair for 1-5 min, andthen rinsed off for 30 sec by running water under controlled flow rate andtemperature conditions. The key is to develop questionnaires which providean adequate product description and to properly select panelists to includeindividuals with varying opinions and perceptions. The rheology, appearance,feel, and texture of the product can be analyzed in terms of the followingparameters: (1) viscosity or ease of dispensing the product from a bottle, (2)feel and texture on the palm before application to hair (oily, hard versus soft,waxy, watery, smooth, rich, tacky), (3) color, (4) spreadability or ease of work-ing the formulation into the hair, and (5) ease of rinse from hair and skin aftertreatment. Hair characteristics are evaluated for (1) ease of wet and dry comb-ing, (2) wet and dry feel, (3) manageability, (4) body, (5) static, (6) luster, and(7) residue on hair. Further analysis of hair condition can be performed aftera single or multiple shampooings with a reapplication of the product. Theproperties of a conditioner which could be judged in this test include (1) re-movability of a treatment from hair by shampooing and (2) buildup as a resultof multiple applications. Rating systems usually employ a scale from 1 to 10, with 10 being the \"toprating\" and 1 the \"bottom rating.\" The ratings given by panelists are averaged

Evaluating Effects of Conditioning Formuiations on Hair 327to give a grade number that can be used to compre various products. Sinceother scales can also be employed, including individual scales for each partici-pating panelist, any scale can be calibrated by calculating the percentage ratingbased on the \"top rating\" characteristic for each test participant. Thus, thecalibration facilitates the comparison of the ratings from panelists employingdifferent rating systems (62). Further discussion of various advantages or dis-advantages of rating systems, including the use of a bipolar scale for liking/dis-liking as well as ratio scaling and magnitude estimation, is given in Ref. 62.2. Salon TestingThe next step following the analysis of hair tresses is prototype screening on asmall scale by an internal expert panel in R&D or by salon testing (63). Salontesting is usually conducted by product formulators together with salon stylists.Before the test is carried out, a salon operator has to make appointments withpanelists possessing a hair type appropriate for a tested product (thin hair,damaged hair, etc). During the actual test, the most widely used procedureinvolves the half-head application of a prototype product with the second half-head left untreated or treated with a control formulation. A variety of hairproperties can be evaluated on both the prototype- and control-treated sideof a head. For conditioners, the key parameters are (1) ease of combing, (2)feel, (3) body, (4) static charge, (5) residue on hair, (6) extent of hair moisturi-zation, (7) buildup upon multiple product application, and (8) removability byshampooing. The test participants also assess the ease of product application,consistency, and color. A detailed questionnaire may be developed includinga rating system and questions similar to those presented in Tables 2 and 3. Theformulator and the stylist participate in product application, and their inputs,in addition to the opinion of a panelist, are included in the test protocol. Sev-eral panelists are usually treated with the same product in order to gather morerepresentative information about the product tested.3. Consumer TestingApart from expert panels, guidance for product development and the evalu-ation of the final product acceptance can be provided by a consumer panelwhich comprises the final users of the product. Consumer panels can be or-ganized for the analysis of various problems related to the development of aproduct, including a descriptive analysis panel, a screening panel, or a qualitycontrol panel. In addition to this, a home-use consumer test serves as a criticalstep in the development of a new conditioner. This type of test may includethe analysis of a single product or a paired comparison of two different prod-ucts. An example of the testing protocol as well as the hypothetical test resultsfor a conditioner designed for chemically processed (damaged) hair is givenin Table 2. The results demonstrate a very favorble consumer reaction to the

328 JachowiczTable 2 Example Protocol for a Home-Use Consumer Test of aConditioner Designed for Chemically Processed, Damaged Hair:One Prototype ProductTotal Respondents 25Purchase intent 19 DefinitelyIprobably would buy 9 10 Definitely would buy 6 Probably would buy 3 Probabfy/deflnitefy would not buy 3 Probably would not buy Definitely would not buy 7Overall opinion 7 Excellent 6 Very good 3 2 Good Fair 2 Poor 2Product consistency 16 Much too thick 3 Somewhat too thick 2 Just about right Somewhat too thin 1 Much too thin 4Fragrance intensity 15 3 Much too strong 2 Somewhat too strong Just about right 10 Somewhat too weak 6 Much too weak 3Comparison to usual brand 4 Much better 2 Somewhat better About the same 59 Somewhat worse 50 Much worseProduct likes 10 Mentioned something liked (total) 7 7 Manageability (total) 5 8 Leaves wet easy to detangle and comb 7 Leave hair easy to style Gives hair body/fullness Doesn't weigh hair down/no residues or buildup Leaves dry hair feeling soft and silky Adds moisture to hair

Evaluating Effects of Conditioning Formuiatlons on IHair 329Tabie 2 Continued 6 5 Does not dull hair 4 Pleasant fragrance/fresh smell/light Light consistency 21Product dislikes 6 Mentioned something disliked 5 4 Leaves hair flat and limp 6 Don't like the fragrance Had to use too much/more than usual 19 Not viscous enough/Too viscous 17Attribute ratings 17 \"Agree completely\" 15 14 Hair easy to comb through when wet 14 Rinses out easily and completely 14 Easy to wash off by shampooing 17 18 Does not leave hair feeling greasy or oily 11 Does not leave hair fly-away or full of static 14 Leaves hair looking and feeling clean 20 18 Leaves dry hair feeling soft and silky 21 Is good for damaged hair Restores moisture to hair Has a pleasant fragrance Leaves hair heahhy looking Does not remove color from hair Leaves hair easy to style Does not remove color from hairHas a nice color 10Has a good consistency 10Easy to work into hair 11Twenty-five white women, ages 18-55, who have chemically processed (oxi-datively dyed, permed, or bleached) their hair within the past 6 months andwho are users of retail-brand cream conditioners three or more times perweek participated in this study. At the company testing center, a productdescription was red to them, and they were given two 6-ounce bottles ofconditioner for damaged hair to use at home for a 3-week period, After 3weeks they were contacted by phone and probed on product usage, likes/dis-likes, purchase interest, overall opinion, and the level of agreement to a listof product attributes.

330 JachowiczTable 3 Example Protocol for a Home-Use Consumer Test of a Conditioner De-signed for Thin Hair: Paired Comparison of Prototype Products A and BTotal respondents 35Overall preference 21 Prefer A 15 A lot 6 A little 14 Prefer B 10 A lot 4 A littlePreference of preferred test product Prefer Product versus usual brand Prefer test product Prefer usual instant conditioner AB No preference Total 14 8 35 32 20 15Preference on attributes Prefer Prefer No A B preferenceAdding body to hair 17 11 7Leaving hair manageable 18 12 5Leaving hair easy to style 19 9 7Improving the state of damaged hair 17 9 9 10 10Not weighing hair down 15 10 11Adding fullness to hair 14 10 12Leaving hair moisturized 13 10 10Being gentle to hair 15 12 11Leaving hair shiny 12 9 12Making hair detangling easy when wet 14 10 10 15 12 10Leaving dry hair being soft and silky 13Not leaving a residue on hair 10 10 13 11Not leaving greasy or oily residue in hair 15 13 11Leaving hair looking and feeling healthy 11 10 10Having a pleasant fragrance 11 14 10Rinsing out easily and completely 15 12 7 11Not leaving hair flyaway with static 13 13 electricity 16 12 10 11 10Leaving hair looking and feeling cleanHaving an appealing color 9Having just the right consistency 3Easy to work into hair 14

Evaluating Effects of Conditioning Formulations on Hair 331Table 3 Continued Prefer Prefer No A B preferencePreference on attributes (continued) 15 12 8 17 10 8 Easy to wash off with a shampoo Leaving hair feeling stiffer with more bounceReasons for preference versus usual brand Prefer Prefer Usual Usual A brand B brandHair characteristics 12 4 7 3 Imparts more body 44 6 2 Easier to comb or detangle 72 5 1 Leaves hair with more volume 81 5 1 No residue or buildup on hair 81 4 3 Leaves dry hair soft and shiny 71 4 —Product characterisdcs Has pleasant scent 52 4 3 Washes off easily with a shampoo Rinses out quickly and completely 83 6 2Total 14 3 8 5Thirty-five white women, ages 18-55, participated in a paired comparison study of products A andB. All paneUsts described themselves as having hair which lacks body. They also declared them-selves users of retail brands of instant conditioner three or more times per week. In order tominimize bias, half of the consumers used formulation A first and half used formulation B first.At the company testing facilities, the participants were given two extra-body conditioners to useat home for a period of 2 weeks. The product to be used during the second week was sealed in aplastic bag and labeled with a date to begin usage. One day before consumers were to switchproducts they were contacted by phone as a reminder. After 2 weeks consumers were contactedby phone and interviewed to determine an overall preference of test products, preference on a listof attributes, and preference of the preferred test product or their usual conditioner.product. Purchase intent is high, and the product is judged by the majority ofrespondents to be better than their usual brand. It also performs all the keyfunctions of a conditioner designed for damaged hair, leaving hair easy tocomb, manageable, and remoisturized. Furthermore, the results indicate thatthe tested conditioner has light consistency, adequate fragrance, and is easyto apply and to rinse off, without leaving an excessive buildup. The second type of consumer test involves a paired comparison of two dif-ferent products. This test may include the use of a new prototype conditionerversus an existing, well-established product (for example, a market leader inthe analyzed product category), or it may offer two prototypes designed for anew product line. The questionnaire may also explore consumers preference

332 Jachowiczin relation to their usual conditioner brand. Table 3 presents the testing pro-tocol and hypothetical test results for a conditioner designed for women withthin hair who expect an increase in hair body as well as detangling benefits. Itcan be concluded from these data that both products A and B are stronglypreferred over the respondents' usual brand. This can be attributed to superiorbenefits of the conditioner defined as \"giving hair more body or volume,\" theability to detangle hair, and the pleasant scent of the formulation. When com-pared to each other, product A is preferred in terms of a number of hair prop-erties such as hair body or fullness, styling ease, manageability, and combabil-ity. Product B appears to be formulated with ingredients characterized by alower affinity to hair, resulting in less residue on hair. Thus, product B is per-ceived as less desirable for restoring moisture to hair and for not improvingthe state of damaged hair. Product B is, however, preferred for rinsing outeasily, for not leaving buildup on hair, and for eliminating electrostatic charg-ing. The overall conclusion from the consumer test described in Table 3 is thatproduct A is a good candidate as an extra-body hair conditioner and meritsfurther product development testing.III. CONCLUSIONS AND FUTURE DEVELOPMENTSThe evaluation of hair conditioners can be performed by both instrumentaland noninstrumental methods. At the present time, noninstrumental methodssuch as panel and consumer testing are predominant, since they are thoughtto best predict consumer preferences for a given product and ultimately itssuccess in the marketplace. The instrumental methods are usually employedin the early stages of product development in the selection of raw materials,and also for the support of claims when the final formulation is prepared. Theuse of quantitative techniques is also mandated by new legislation requiringextensive support data demonstrating the effectiveness of cosmetic productsand by the widespread use of competitive claims. While the methods of sensoryanalysis are being constantly refined and improved, there has also been sig-nificant progress in physicochemical evaluation techniques. These methodsare becoming more automated and computerized, and can frequently provideseveral physicochemical parameters simultaneously, resulting in a precise andmultifaceted description of physical phenomena connected with the processof hair conditioning. Unlike panel or consumer tests, which measure the per-ception of conditioning effects in terms of a few descriptors well understoodby the panelists but not well defined from a physicochemical point of view, theinstrumental methods yield precise, quantitative information which is some-times difficult to relate to human perceptions. However, future developmentof even more sophisticated quantitative techniques, especially in the area ofmechanical measurements (texture analysis, dynamic mechanical analysis),

Evaluating Effects of Conditioning Formulations on Hair 333image analysis, and adsorption/desorption techniques should be able to bridgethe gap between sensory perception and the physicochemical description ofconditioning phenomena.REFERENCES 1. Jachowicz J. Hair damage and attempts to its repair. J Soc Cosmet Chem 1987; 38:263. 2. Tate ML, Kamath YK, Ruetsch SB, Weigmann H-D. Quantification and preven- tion of hair damage. J Soc Cosmet Chem 1993; 44(6):347. 3. Jachowicz J, Helioff M, Rocafort C, Alexander A, Chaudhuri RK. Photodegrada- tion of hair and its photoprotection by a substantive photofilter. Drug & Cosmetic Industry, December, 1995, 4. Franbourg A. Synchrotron light: A powerful tool for the analysis of human hair damage. 10th International Hair-Science Symposium, Rostock, 1996. 5. Cooley AJ. The toilet and cosmetic arts in ancient and modern times. Published by Burt Franklin, New York, 1866, reprinted 1970. 6. Davies JT, Rideal EK. Interfacial Phenomena, New York: Academic Press, 1963. 7. Owens MJ. The surface activity of silicones: A short review. Ind Eng Chem Prod Res Dev 1980; 19(1):97. 8. Finkelstein P, Laden K, The mechanism of conditioning of hair with alkyl quater- nary ammonium compounds. Appl Polym Symp 1971; 18:673. 9. Scott GV, Robbins CR, Barnhurst JD. Sorption of Quaternary Ammonium Sur- factants by Human Hair. J Soc Cosmet Chem 1969; 20:135.10. Chow CD. Interaction between polyethyleneimine and human hair. Text Res J 1971; 41:444.11. Woodward J. Aziridine chemistiy—applications for cosmetics. J Soc Cosmet Chem 1972; 23:593.12. Goddard ED, Faucher JA, Scott RJ, Tumey ME. J Soc Cosmet Chem 1975; 26:539.13. Faucher JA, Goddard ED. Influence of surfactants on the sorption of a cationic polymer by keratinous substrate. J Coll Int Sci 1976; 55:313.14. Jachowicz J, Berthiaume M, Garcia M. The effect of the amphiprotic nature of human hair keratin on the adsorption of high charge density cationic polyelectro- lytes. Coll Polym Sci 1985; 263:847.15. Goddard ED, Harris WC. Substantivity to keratin as measured by X-ray photo- electron spectroscopy (XPS) and electrokinetics (EK). Preprints of the XlVth IFSCC Congress, Barcelona, 1986, Vol. II, p, 1039.16. Goddard ED, Harris WC. An ESCA study of the substantivity of conditioning polymers on hair substrates. J Soc Cosmet Chem 1987; 38(4):233.17. Kamath YK, Dansizer CJ, Weigmann H-D, Surface wettability of human hair. I. Effect of deposition of polymers and surfactants. J Appl Polym Sci 1984; 29:1011.18. Jachowicz J, Williams C, Maxey S. Sorption/Desorption of ions by Dynamic Elec- trokinetic and Permeability Analysis of fiber plugs. Langmuir 1993; 9(11):3085.19. Karjala SA, Williamson JE, Karler A. Studies of the substantivity of collagen de- rived polypeptides to human hair. J Soc Cosmet Chem 1966; 17:513.

334 Jachowicz20. Turowski A, Adelmann-Grill BC, Substantivity to hair and skin of 125-I-labelled collagen hydrolisates under application simulating conditions. Int J Soc Cosmet Sci 1985; 7:71,21. Mintz GR, Reinhart GM, Lent B. Relationship between collagen hydrolisate mo- lecular weight and peptide substantivity to hair. J Soc Cosmet Chem 1991; 42:35.22. Newman W, Cohen GL, Hayes C, A quantitative characterization of combing force. J Soc Cosmet Chem 1973; 24:773.23. Tolgyesi WS, Cottington E, Fookson A. Mechanics of hair combing. Presented at the Symposium on Mechanics of Fibrous Structures, Fiber Society, Atlanta, May, 1975,24. Garcia ML, Diaz J. Combability measurements on human hair. J Soc Cosmet Chem 1976; 27:379.25. Kamath YK, Weigmann H-D. Measurement of combing forces, J Soc Cosmet Chem 1986; 37:11.26. Jachowicz J, Helioff M. Spatially-resolved combing analysis. Present at SCC An- nual Scientific Meeting, New York, December 1995; J Soc Cosmet Chem, in press.27. Hambidge A, Wolfram L. Effect of comb materials on hair combing. 4th Interna- tional Hair Science Symposium, Syburg, Germany, 1984.28. Firstenberg DE, Rigoletto R, Moral L. SCC Annual Scientific Seminar, New York, May 1997, Preprints, p. 36.29. Robbins CR, Crawford R, Cuticle damage and the tensile properties of human hair. J Soc Cosmet Chem 1991; 42:59.30. Rushton H, Kingsley P, Treating reduced hair volume in women. Cosmetics & Toiletries 1993; 108(3):59.31. Hough P, Hey EJ, Tolgyesi WS. Hair body. J Soc Cosmet Chem 1976; 27:571.32. Yin NE, Kissinger RH, Tolgyesi WS, Cottington EM. The effect of fiber diameter on the cosmetic aspects of hair. J Soc Cosmet Chem 1977; 28:139.33. Garcia ML, Wolfram U. Presented at the 10th IFSCC Congress, Sydney, Austra- lia, 1978.34. Robbins CR, Crawford RJ. A method to evaluate hair body, J Soc Cosmet Chem 1984; 35:369.35. Kamath YK, Weigmann HD. Evaluation of hair body. SCC Annual Scientific Meeting, New York, December 1996, Preprints, p. 19.36. Clarke J, Robbins CR, Reich C. Influences of hair volume and texture on hair body of tresses. J Soc Cosmet Chem 1991; 42:341.37. Stamm RF, Garcia ML, Fuchs JJ. The optical properties of human hair. Parts I and II, J Soc Cosmet Chem 1977; 28:571.38. Bustard HK, Smith RW. Studies of factors affecting light scattering by individual human hair fibers. Int J Cosmet Chem 1990; 12:121.39. Reich C, Robbins CR. Light scattering and shine measurements of human hair: A sensitive probe of the hair surface. J Soc Cosmet Chem 1993; 44:221.40. Czepluch W, Hohm G, Tolkiehn K. Gloss of hair surfaces: Problems of visual evaluation and possibilities for goniophotometric measurements of treated strands, J Soc Cosmet Chem 1993; 44:299,41. Maeda T, Hara T, Okada M, Watanabe H. Measurements of hair luster by color image analysis. 16th IFSCC Congress, New York, 1990, Preprints, Vol. I, p. 127.

Evaluating Effects of Conditioning Formulations on Hair 33542. Jachowicz J. Fingerprinting of cosmetic formulations by dynamic electrokinetic and permeability analysis. II. Hair conditioners. J Soc Cosmet Chem 1995; 46.43. Jachowicz J, Berthiaume M. Microemulsions vs macroemulsions in hair care prod- ucts. Cosmetics & Toiletries 1993; 108(3):65.44. The effect of reactive treatments on hair by Dynamic Electrokinetic and Perme- ability Analysis. 9th International Haire Science Symposium, Prien, 1994.45. Kamath YK, Dansizer CJ, Weigmann H-D. Wettability of keratin fiber surfaces. J Soc Cosmet Chem 1977; 28:273.46. Kamath YK, Dansizer CJ, Weigmann H-D. Wetting behavior of human hair fibers. J Appl Polym Sci 1978; 22:2295.47. Kamath YK, Dansizer CJ, Weigmann H-D. Surface wettability of human hair. II, Effect of temperature on the deposition of polymers and surfactants. J Appl Polym Sci 1985; 30:925.48. Kamath Y, Dansizer CJ, Weigmann H-D. Marangoni effect in water wetting of surfactant coated human hair fibers. J Coll Int Sci 1984; 102(1):164.49. Kamath YK, Dansizer CJ, Weigmann H-D. Surface wettability of human hair. III. Role of surfactants in the surface deposition of cationic polymers. J Appl Polym Sci 1985; 30:937.50. Weigmann H-D, Kamath YK, Reutsch SB, Busch P, Tesmann H. Characterization of surface deposits on human hair fibers. J Soc Cosmet Chem 1990; 41:379.51. Martin AJP. Triboelectricity in wool and hair. Proc Phys Soc Lond 1940; 53(2):186.52. Jachowicz J, Wis-Surel G, Wolfram L. Directional triboelectric effect in keratin fibers. Text Res J 1984; 54(7):492.53. Lunn AC, Evans RE. The electrostatic properties of human hair. J Soc Cosmet Chem 1977; 28:549.54. Jachowicz J, Wis-Surel G, Garcia ML. Relationship between triboelectric charging and surface modifications of human hair. J Soc Cosmet Chem 1985; 36:189.55. Patel CV. Antistatic properties of some cationic polymers used in hair care prod- ucts. Int J Cosmet Sci 1983; 5(5): 181.56. Jachowicz J, Garcia M, Wis-Surel G. Relationship between triboelectric charging and surface modification of human hair: Polymeric versus monomeric long alkyl chain quaternary ammonium salts. Text Res J 1987; 57(9):543.57. Jachowicz J, Wis-Surel G, Garcia ML. Further observations on triboelectric charg- ing effects in keratin fibers. Polymers for Advanced Technologies, lUPAC Inter- national Symposium, Jerusalem 1987, M Lewin, ed.. New York: VCH Publishers, 1988, pp. 340-360.58. Wis-Surel G, Jachowicz J, Garcia ML. Triboelectric charge distributions generated during combing of hair tresses. J Soc Cosmet Chem 1987; 38:341.59. Crawford RJ, Robbins CR. A replacement for Rubine dye for detecting cationics on keratin. J Soc Cosmet Chem 1980; 31:273.60. Swift JA, Brown AC. The critical determination of fine changes in the surface architecture of human hair due to cosmetic treatment. J Soc Cosmet Chem 1972; 23:695,61. Robinson VNE. A study of damaged hair. J Soc Cosmet Chem 1976; 27:155.62. Moskowitz HR. Cosmetic product testing. New York: Marcel Dekker, Inc., 1984.

336 Jachowicz63. Ciyer PH. Design and analysis of product performance trials in a hairdressing salon. Cosmetic Science, Proceedings of the Second Congress of the IFSCC, AW Middleton, ed.. New York: Pergamon Press Book, 1962.64. Close J-A. The concept of sensory quality. J Soc Cosmet Chem 1994; 45:95.65. Stone H, Sidel JL. Sensory evaluation practices. San Diego, Academic Press, 1993.

14Evaluating Performance Benefits ofConditioning Formulations onHuman SkinRonald L. Rizer and Monya L SiglerThomas J. Stephens & Associates, Inc., Carrollton, TexasDavid L MillerCuDermlBionet, Inc., Dallas, TexasI. INTRODUCTIONGreat strides have been made in our understanding of the mechanism of actionof skin care products designed to condition the skin. This progress can beattributed to both an increased knowledge of the function of the skin as wellas the development of new technologies used to measure the benefits of \"con-ditioning\" products. In this context, the term \"conditioning\" is defined as animprovement in a definable skin attribute. For instance, an effective moistur-izer conditions or improves the attribute dry skin by enabling the stratum cor-neum to hold optimal levels of water more effectively, by helping to soften therough, dry skin surface, and by altering the pattern of desquamation, allowingcorneocytes to slough as discrete units rather than as clusters of aggregatedcells which form dry skin flakes. Other attributes of skin that a conditioningproduct may benefit or improve include oily skin, large facial pores, skin irri-tation, and photodamage. Photodamage is a broad term for skin damage thathas resulted as a consequence of years of unprotected sun exposure, and isusually manifested by increases in fine lines, wrinkles, mottled pigmentation,pigmented spots, skin looseness, and sallowness. Photodamaged skin is often 337

338 Rizer et al.referred to as photoaged skin, and it is distinguished from intrinsic skin aging,which results from the passage of time. Photodamaged skin is widespread inthe population, and thus the market is saturated with skin care products claim-ing to improve this condition. The effects of conditioning formulations on the skin are often subtle. Muchscientific and clinical research energy has been expended in the latter half ofthe twentieth century trying to develop techniques for reliably detecting thechanges in skin accompanying application and use of conditioning and othertherapeutic formulations. There have been \"inspirational\" achievements thathave led the way for development of many of the techniques in use today.The citations below do not necessarily represent the most complete, earli-est, or most definitive treatment of the subject, which will always be \"work inprogress.\" For skin dryness, validated grading scales were developed allowing for morereliable clinical assessment by the investigator (1,2). The use of adhesive ma-terials to remove samples of stratum comeum scales for careful ex-vivo assess-ment was pioneered by Goldschmidt and Kligman (3). Prall introduced theconcept of measurement of scattering and reflection of white light by scalesheld on adhesive substrates, which allowed elegant discrimination of variousdegrees of scaling (4). Today we have computerized image analysis of scalessampled on commercially available clear adhesive disks designed expressly forthis purpose (5). For examining the texture of the skin surface, technology has progressedalong two paths: close-up photography and assessment of silicone replicas ofthe surface. While many unremarkable photographic techniques have beenemployed to record changes in the appearance of skin, it was the applicationof polarized light photography (6) that opened a truly unique way of docu-menting the skin surface. Viewing the skin under cross-polarized light revealsdetails of the skin pigmentation and sub-stratum corneum features not readilyvisible under normal lighting, whereas viewing under parallel-polarized lightaccentuates the texture of the stratum comeum scales, and surface topogra-phy. The analysis of silicone replicas of the skin surface was extensively devel-oped by Cook (7). Cook employed surface characterization tools in use at thattime in measuring the smoothness of machined metal surfaces. While thesetechniques eventually proved much too sensitive to be used in characterizingthe rather coarse skin surface (compared to machined metals), adaptation ofother methods such as computerized image analysis (8) and laser profilometry(9) has proved most successful in detecting changes in the surface texture con-dition of the skin. Electrical measurements of the skin comprise relatively simple-to-applymethods often used to evaluate skin moisturizers. Several instruments basedon skin capacitance and impedance are commercially available (10). The

Evaluating Conditioning Formulations on Human Skin 339difficulty has been in the interpretation of the data produced by these instru-ments. In 1983, Leveque and deRegal (11) reviewed the various techniques inthe literature at that time and provided clear interpretation guidelines. In par-ticular, they pointed out that electrical techniques are most responsive to thewater content of the stratum comeum layer; therefore only those conditioningcomponents that actually alter water content will be detected. Conditioningcomponents that address lubricity, for example, are not measured, althoughthey can have a profound influence on the overall effectiveness of a moistur-izer. For instance, emollients coat the skin surface and sorb into the upperlayers of the stratum corneum, making the skin appear shinier, smoother, andless rough, but typically have little or no effect on the water-holding capacityof the stratum corneum. A key achievement of the last decade is not attributable to any one person.This has been a decade of development of more than a dozen commercialinstruments designed specifically to aid in clinical evaluation of the skin. Thetechnology has moved from the awkward \"training wheels\" stage of impracti-cal laboratory designs to convenient clinical instruments. A review of theseinstruments in any depth is beyond the scope of the present chapter. Thereader is encouraged to pursue two recent books (12,13) which cover theseinstruments and many other useful techniques in detail. In this chapter we describe a five-pronged approach to substantiate productperformance claims. This approach includes (a) the importance of panel se-lection, (b) human perception of product benefit, (c) clinical assessment andphotodocumentation of product benefit, (d) objective assessment of productbenefit using biophysical methods, and (e) statistically based conclusions.Moreover, we discuss why one must take into account skin complexity, andskin variables such as race, gender, anatomical location, climate, lifestyle, oc-cupation, age, and undefined factors when designing studies. Lastly, we de-scribe selected testing methodologies that are relevant to the success of today'sskin care product mix.II. FIVE-PRONGED APPROACH TO SUBSTANTIATE PRODUCT PERFORMANCE CLAIMSA. Why Is a Multlpronged Approach Desirable (and Necessary) In Substantiating Product Performance Claims?Product sales are often driven by performance and safety claims. Someexamples of product claims are \"reduces fine lines,\" \"moisturizes for up to 12hours,\" and \"nonirritating and safe in normal use.\" A single clinical or bio-physical approach might be used to provide substantiation for any of these

340 Rizer et al.examples. However, such an approach is rarely sufficient to characterize aproduct's benefit, which can lead to support for a false claim. This occurs be-cause a single, unidimensional technique does not constitute a method power-ful enough to assess the complex interactions that occur when a test productis applied to the skin. One of the most challenging tasks in supporting a claim is providing crediblesupporting data. The multipronged approach addresses this issue by employ-ing a series of methods to assess the multifaceted benefits of a product's inter-action with the skin. Our method is rooted in an understanding of the anatomyand physiology of the skin and the tools available to measure product effectsat the level that they are occurring. Our approach is strengthened by a historyof experience in extracting subjective information from panelists about theirexperiences while using a test product. Lastly, we choose the most appropriatemethod of analysis and presentation of the data to draw conclusions that pro-vide credible substantiation of product claims.B. Part I of the Five-Pronged Approach: Panelist SelectionThe success of a clinical trial is dependent on the screening of prospectivecandidates and the selection of qualified subjects. Certain biological factorsprovide obvious recruiting guidelines. A few such examples are gender, age,and cutaneous conditions or symptoms. For example, consider a study whosegoal is to evaluate the efficacy of a facial lotion designed for women to reducethe appearance of fine lines around the eyes. The first goal of recruiting wouldbe to eliminate males, and young women who do not have facial fine lines. Inorder to provide a successful study, however, recruiting efforts must reach farbeyond the basic, well-stated parameters of the study. An example of moresubtle (but important) recruiting techniques is illustrated below.1. Cosmetic InteractionsIndividuals should be excluded from a study who have a recent history of usinga cosmetic that contains the same active ingredient as the product being tested.Examples include alpha-hydroxy acids, beta-hydroxy acids, and retinoids.2. Drug InteractionsCertain medications may interact with a product's active ingredient or maymask adverse reactions resulting from product usage. Such drugs include an-tiinflammatory agents, contraceptives, and androgens. Other medications mayinduce skin sensitivity to sunlight.

Evaluating Conditioning Formulations on Human Skin 3413. Habits and PracticesThe lifestyle habits and practices of individuals can affect the outcome of astudy in certain cases. For instance, individuals who use tanning salons or whoare exposed to sunlight as part of their occupation should not participate in astudy designed to test a skin lightening product. The selection of habits andpractices that are used to screen individuals is dependent on the product beingtested and the objective of the study,4. Severity of SymptomsThe selection of a panelist should not be determined solely on an individualpossessing the desired cutaneous characteristic(s). Of equal importance is theexclusion of those whose condition could be too severe to enable the test ma-terial to produce the anticipated effect. In the case of qualifying subjects, moreis not always better.5. Identifying Speciailzed PopuiationsA specialized population refers to a group of individuals who all possess awell-defined cutaneous attribute such as sensitive skin (14,15), dry or chappedskin, atopic dermatitis, winter itch, rosacea, acne, or cellulite. The screeningof individuals for such conditions requires the formulation of a series of ques-tions that accurately defines the condition on a clinical level. At the same time,the questions must be worded so that the volunteer study panelists understandthem and respond to them appropriately based on their individual experienceswith the condition.6. Ett)nic PopulationsCompanies with global markets can choose to test their products with specificethnic populations in the United States, or they can perform the tests in coun-tries whose population represents their ethnic choice. Both options providecertain benefits. For instance, skin sensitivity varies in many subtle ways (16),and formulating skin care products to address this issue may determine thesuccess or failure in a foreign market. Premarketing testing in such ethnicpopulations can be crucial in assuring success in challenging foreign markets.C. Part li of the Five-Pronged Approach: Human Perception of Product BenefitThe panelists' perception of how a test product performs is possibly the mostrelevant dimension in product testing. Frequently the subjects' perceptionof product benefit exceeds that which is captured by clinical grading or bio-physical measurements. We obtain information from subjects regarding theirperception of test products via questionnaires and poststudy focus group

342 Rizer et al.interviews. The following section outlines our experience in capturing sub-jective information from panelists regarding their experience in using a testproduct.1. QuestionnairesWritten questionnaires can be administered to subjects at intervals throughoutthe course of a study and/or at the conclusion of product use. They are notonly useful in capturing information about product benefit, they may also beused to inquire about cosmetic preferences, intent to purchase, comparison totheir regular brand, or product packaging and delivery. Responses to ques-tionnaires may also provide useful information for selecting the most desirableparticipants for inclusion in a focus group (see below). Properly designed ques-tionnaires are balanced so that the responder to a given question must choosefrom one or more positive responses, a neutral response, and one or morenegative responses (the number of positive and negative choices must bal-ance). Some questions require a \"yes\" or \"no\" answer, or a short narrativedescription.2, Focus Group InterviewsFocus groups provide a unique forum for capturing feedback about subjects'thoughts and feelings regarding their experience using a test product. A mod-erator serves to initiate and guide the topics for discussion. The ensuing inter-active group discussion about the subjects' experiences while using the productprovides a wealth of dynamic information that cannot be obtained from writ-ten questionnaires alone. One of the most important aspects of conducting a successful focus groupis the selection of panelists. The selection process is dependent on the specificinformation desired about the test products. For instance, if broad feedbackis desired, then the selection process might be a random one, where the focusgroup population is representative of the study population. However, onemight prefer to restrict the group to individuals who responded to the pos-tusage questionnaires in a certain way. For instance, if some of the subjectsexpressed displeasure with some aspect of the product or the way in which itwas used or dispensed from the container, then a session with these individualscould be used to learn more about the nature of the specific problem. Focusgroup panels can also be chosen based on demographics, such as age, skin type,or race. Each focus group session is designed to last approximately 1 hour and usu-ally takes place with a group of about 10 test subjects. The number of subjectsinterviewed in a session is kept low to encourage each member's participationin the discussion. Multiple groups can be interviewed in succession if a largenumber of participants is desired. To optimize interactions between subjects

Evaluating Conditioning Formulations on Human Skin 343and the moderator, sessions are held in a large conference room, whereparticipants can sit facing one another. The facility is also equipped with aseparate, candid viewing room, where sessions can be privately monitored andvideotaped. While the information obtained from focus groups is dynamic,it is generally not quantitative, since group sizes are too small. The infor-mation obtained is qualitative and therefore not statistically significant.Nevertheless, this information can be some of the most valuable informa-tion one can obtain.D. Part III of the Five-Pronged Approach: Clinical Assessment and Photodocumentatlon1. Clinical AssessmentClinical assessment involves careful inspection of the skin, usually undermagnification and blue daylight lighting, by a technician or physician trainedto grade the full range of a skin attribute. Clinical grading can be particularlybeneficial for assessing skin attributes that are not easily measured with bioin-strumentation. Examples of such attributes are scaling and cupping on the lips,dark circles and puffiness of the eyes, and roughness of calloused skin of theelbows and knees. Clinical grading is especially powerful when combined withhigh-quality clinical documentation photography. A product that effectively conditions the skin will produce changes in char-acteristics that can be perceived and graded by sight or touch. Severity of in-tensity or degree of improvement can be assessed using a 10-cm analog scale(10-cm line scale) so that changes in an attribute can be quantitated andpercent changes from baseline reported. This method of clinical assessmentof a product benefit can support claims like \"40% improvement in fine lines.\"Clinical grading can be a simple ranking of an attribute as \"mild,\" \"moderate,\"or \"severe.\" A common application of this method is for assessing erythema(redness), edema (swelling), and dryness/scaling, and subclinical irritation,such as burning, stinging, itching, tightness, or tingling. a. Photodamage. Most of the attributes listed here are normally gradedon the face, although some can also be accurately assessed on the chest and hands,which are the primary areas of concern for most women who have experiencedyears of unprotected sun exposure. Asterisks indicate attributes best suited forsupport with clinical documentation photography (see next section). *Fine lines and wrinkles Looseness/firmness *Sallowness * Mottled pigmentation *Skin clarity

344 Rizer et al. Tactile roughness *Skin crepeness b. Dry/Chapped Lips * Cupping (small oval depressions on the lips due to dryness) *Fine lines * Cracking *Fissuring c. Dry Skin and Irritation. These attributes can be assessed on any area ofthe body including the scalp. Subjective symptoms of irritation (burning, sting-ing, itching, tightness, and tingling) are assessed by questioning the subjectduring the examination. * Scaling * Cracking Tactile roughness * Erythema Edema d. Other Skin Characteristics *Eye puffiness *Dark circles * Calloused skin Cellulite2. Clinical Documentation PhotographyPhotography lends credibility to the results obtained from clinical grading ofcertain skin attributes (see items above marked with an asterisk). Photographstaken prior to product use and at subsequent study visits provide a visual illus-tration of the gradual benefits that a test product provides. A variety of pho-tographic options are available for capturing the benefits of a test product. Thechoice of method should best reflect the skin parameter that the product istargeting. Examples of how some photographic methods accentuate differentskin characteristics is illustrated in the following section. The photographicmethods that are used most often are visible light photography, reflected ul-traviolet light photography, and cross-polarized light photography. Descrip-tions of these methods and demonstrations of their unique contributions toclaim substantiation are discussed below. a. Visible Light Photography. Visible light photography—usually colorphotos are best—relies heavily on lighting and shadows to document texturalfacial features such as fine lines, wrinkles, dryness, scaling, and other features(Figures 1 and 2).

Evaluating Conditioning Formulations on Human Skin 345 b. Reflected Ultraviolet (UV) Light Photography. This type of photographyis useful for highlighting pigmentation of the skin that is not apparent withvisible light photography. Thus, it is a helpful tool in documenting improve-ments produced by skin-lightening products or products designed to reducethe appearance of photodamage and aging (Figures 3 and 4). c. Cross-Polarized Light Photography. Cross-polarized light photogra-phy—^usually color photos are best—reduces reflection of light from the sur-face of the skin, thereby eliminating the shiny appearance and/or glare thatcan accompany visible light photography. This technique is particularly helpfulin accentuating the inflammatory nature of acne lesions, and telangiectasia,which is red, finely branching skin capillaries typically found on the nose,cheeks, and chin (Figures 5 and 6).E. Part IV of the Five-Pronged Approach: Biophysical iVIethodsAn integral part of claim substantiation is the ability to support clinical gradingand panelists' perception of product benefit with objective biophysical meas-urements. Such measurements provide technical support for the more subjec-tively based results obtained with clinical grading. Full-service clinical researchlaboratories are equipped with the biophysical instrumentation needed to pro-vide at least one means of support for each of the clinical grading parametersshown in Part I. A brief description of selected biophysical methods and in-strumentation is given below.1. Capacitance MeasurementsThe NOVA Dermal Phase Meter (DPM) uses an electrical capacitance methodto detect changes in the relative moisture content of the stratum corneum. Thisdevice is commonly used to test the efficacy of lotions or creams in deliveringmoisture to the skin or retaining the moisture present in the skin. The SKICON Skin Surface Hydrometer uses electrical capacitance andconductance to detect the micro water content in the superficial portion of thestratum corneum. It is useful for assessing the therapeutic efficacy of topicalagents to deliver and hold water at the skin surface. Like the NOVA DermalPhase Meter, the SKICON Skin Surface Hydrometer is used to evaluate theeffects of moisturizers and other cosmetics on the stratum corneum, and theeffects of chemicals such as surfactants on the stratum corneum. Both instruments can be applied to Tagami's (12) \"sorption-desorption\"technique to evaluate the water-holding properties of the stratum corneum.Essentially, a droplet of water is applied to the skin, wiped dry after 10 sec,and a reading is taken; thereafter, a reading is taken every 30 sec for 3 min.

346 Rtzer et al.Flyure 1 Photographs iUusiraling the ability to document scaling, fine lines, and wrin-kles that accompany (A) dry chapped skin on the lips as well as (B) wrinkles and finelines of the periocular eye area.

Evaluating Conditioning Formulations on Human Skin 347Rgure 2 These photographs illustrate the ability of photography to capture dryness,scaling, and calloused skin on the heels. The (A) before and (B) after photos illustratethe ability to show detailed improvements in scaling and dryness that accompanied theuse of an alpha-hydroxy add (AHA) body moisturizer.

348 Rlzar et al.Rgura 3 These photographs illustrate the dramatic differences between document-ing hyperpigmentation on the face with (A) standard black-and-white photos com-pared to (B) black-and-white reflected UV-light photographs.

Evaluating CofxlHkMiIng Fofmulationi on Human Skin 349Figure 4 The (A) before and (B) after reflected UV-light photos shown here dem-onstrate the ability to capture dramatic changes in mottled pigmentation after treat-ment with an alpha-hydroxy acid (AHA)/reiinol facial moisturizer.

350 Rtzar et al.Rgure 5 This black-and-white photograph illustrates the effect of using cross-polari-zation in documenting acne. Notice that the lesions appear pronounced due to theemphasis of inflammation in the papules and the contrast of the inflammation andwhite within the pustules. Color photographs are superior to black and white, becausethe cross-polarized filter accentuates the red tones.The area under the decay curve is the water-holding capacity (WHC) andrelates to the capacity of the stratum comcum to retain water.2. Transepidermal Water Loss Measurements (17)TTie ScrvoMed Evaporimcter is used to measure the transepidermal water loss(TEWL) and provides an estimate of the integrity of the stratum comcum orbarrier function. This device is used throughout the course of a study to deter-mine if there are changes in the integrity of the stratum a)rncum as a result ofnormal product use or exposure to product under exaggerated conditions.3. Skin Elasticity MeasurementsThe Ballistometer (Hargens) (18,19) is a pendulum device used to measurethe clastic properties of the skin in vivo. This instrument is used mainly on the

Evaluating Conditioning Formulations on Human Skin 351FIgura 6 These photographs illustrate the superiority of (A) cross-polarized lightover (B) visible light photography in accentuating compacted pores of the nose andtelangiectasia. Also note that the lightly pigmented areas (photodamage) are morevisible in the cross-polarized photograph.

352 Rizer et al.face and most commonly on the crow's feet area of the eye. Measurements aretaken throughout a study to document potential benefits from the use of facialor eye area products designed to firm the skin. The Cutometer SEM 474 (20) is a device that also provides informationabout skin elasticity (see Ballistometer above). The Cutometer estimates elas-tic properties of the skin by applying a precisely controlled vacuum to a smalldefined area of skin. The measurements provide information about extensi-bility, resiliency, recoil, and viscous loss. The portability of the Cutometer'sprobe and its laptop computer interface present few restrictions in choosinglocations for measurements.4. Parallel and Cross-Polarized Light Video Imaging System (21)The Zeiss DermaVision system allows images of skin characteristics to be takenat a magnification that exceeds conventional photographic methods. Magni-fied images of features such as pores, hairs, and individual pigmented spotscan be digitized for image analysis of the size, frequency, and color intensityof cutaneous features.5. Sl<in Color MeasurementsThe Minolta Tri-Stimulus Colorimeter measures skin luminosity and chromatic-ity (22). The instrument records color in a three-dimensional space designatedL*fl*6*. The luminance (L*) value expresses the relative brightness of thecolor ranging from black to white, and the a * and b* are the two componentsof chromaticity. The a* value is the color hue ranging from red (-I-) to green(-). The b* value is the color hue ranging from blue (-) to yellow (+).6. Squametry (Desquamation Assessment)D-Squame adhesive disks (CuDerm, Inc.) (23) are small adhesive disks placedonto the skin that are used to sample the outermost layer of the stratum cor-neum. The patterns and thickness of the layers of comeocytes that remain onthe disk upon removal are used to calculate the coarse and fine flakes and thedesquamation index. These parameters, when measured over the course of astudy, are sensitive to treatment effects and will increase when the skin be-comes dry or irritated.7. Sebum MeasurementsSebutape patches (24) are devices used to measure the rate of sebum excretionand/or the distribution of active sebaceous glands. Estimates of these parame-ters are derived from image analysis of the transparent patterns left by facialoils deposited into the pores of the microporous, opaque tape. The sebum-filled pores in the tape are no longer capable of scattering light, so they appeartransparent compared to the air-filled pores of the surrounding tape.

Evaluating Conditioning Formulations on Human Skin 3538. Measurement of Fine Lines and Wrinl<iesSilicone replicas provide a sturdy model (a negative impression) of the finelines and wrinkles present on an area of the skin, such as the face. The replicasare routinely evaluated using optical profilometry and image analysis to countand estimate the relative depth of the wrinkle and fine line features. Replicasare commonly taken on the crow's feet area of the eye to monitor the treat-ment effects of facial products designed to reduce the signs of photodamageor aging. Examples of how we use some of the bioinstrumentation techniques dis-cussed above are illustrated in Figures 7, 8, and 9.F. Part V of the Five-Pronged Approach: Statistically Based ConclusionsData analysis is as important as experimental design and execution in deter-mining the success of a study. Analysis methods are chosen that extract themost information from the data and therefore provide the most general infer-ences. The choice of analytical techniques depends on (a) the informationgoals of the study sponsor and (b) the fundamental characteristics of the col-lected data. A frequently used design specifies that observations from clinical gradingand other measurements are collected at an initial assessment visit, called thebaseline visit, and at subsequent assessment visits. This design introduces atime dimension into the study. Post-baseline visit data is compared with base-line data in order to determine whether changes have occurred that are attrib-utable to product use rather than random chance. Therefore the time dimen-sion is used to investigate product effects. Another experimental design aspect provides a method to compare multi-ple products by establishing multiple treatment groups of subjects. This allowsobservations to be collected for each product over time, including at baseline.Postbaseline data is normalized with baseline data for each product, and thenproducts may be compared against one another. Comparisons are frequentlymade between treatments and controls, test products and standard products,and between different product formulations.1. Information GoalsSponsors' information goals help determine data management and analysismethods. This idea is perhaps best illustrated with an example. We assume thattwo products are to be distinguished in terms of performance and that the inter-action between ethnicity and performance is to be evaluated. This is initiallyachieved by employing two subsamples of subjects from the two ethnic groups ofinterest—say, groups A and B. Both groups use both products—say, X and Y.

354 Rlz»retaJ. NOVAFigure 7 (A) The NOVA Dermal Phase Meter being used in a kinetic dry skin studyon the lower leg- NOVA measurements were recorded at baseline and at 1, 2,3, and24 hr after two different test lotions were applied to treatment sites. (B) The data forthis study. Analysis of the dau showed significant differences (p s .05) between Lotion2 and Lotion 1 in its ability to moisturize the stratum comeum.

Evaluating Conditioning Fonnulatlons on Human Skin 3SSFigure 8 (A) The ScrvoMed Evaporimeter and (B) the NOVA Dermal Phase Meter.These instruments can be used in conjunaion to provide substantiation for claims ofmoisturization and improvement in barrier function (transepidermal water loss). (C)The graph shows the barrier enhancement effect of Lotion B compared to Lotion Aand control. With moisturization studies, transepidermal water loss (TEWL) and rela-tive moisturization (NOVA) measurements usually exhibit an inverse relationship inresponse to treatment. (confrnuecO

356 Rlzer et al.Rgura 8 Continued.Therefore four treatment groups are in operation: AX, AY, BX, and BY. Per-formance measurements are taken at baseline and at subsequent assessmentvisits. The data from the postbaselinc visits are treated by controlling for base-line variable values, leaving us with baseline-normalized data for each p>ost-baseline visit for each of the four treatment groups. At each postbaseline visita comparison may be made between the treatment groups. Tliis allows us toinvestigate simultaneously any potentially subtle ethnic-produa interactionsthat may exist, as well as to compare the products X and Y. However, theanalysis is not complete, since more information may be extracted from thedata. When the AX and BX groups and the AY and BY groujjs are combinedto produce just two groups—X and Y—we are able to generate a pure productcomparison at each post-baseline time point that is more powerful than thecomparison involving four treatment groups. In this example, multiple sponsorinformation goals are achieved by grouping the data.2. Fundamental Data CharacteristicsAnalysis techniques arc selected to match the properties of the study data. De-terminants of data properties include experimental design and the fundamental

Figure 9 (A) The Zeiss DcrmaVision system. (B) Photographs taken with this deviceillustrate the ability of cross-polarized light video to reduce surface features and en-hance the visibility of a single pigmented spot, in this case an actinic lentigines lesion.Moving horizontally, notice the gradual fading of the spot at consecutive time pointsafter treatment with the alpha-hydroxy acid (AHA)/rctinoid test product. 357

358 Rlzer et al.nature of the measurements made. For example, a test subject who uses aproduct during the entire course of a study generates paired observations thatmay be examined for departures from zero in order to determine the existenceof product effects. In another situation a test subject may use a product untila certain threshold is reached, at which time the subject's participation in thestudy ends. The data collected in this case would be survival observations ofthe time taken to reach the threshold. In the first example, standard univari-ate techniques (such as f-tests) could be used to establish product effects,and multivariable techniques (such as ANOVA) may be implemented tocompare products. In the second example, survival analysis methods could beused to examine a single product or to compare multiple products. The pre-ceding examples can also be used to illustrate the differences between datadistributions: measurements taken over time for performance variables maywell be approximately normally distributed, whereas measurements of the timeelapsed until some event occurs are clearly not.III. SELECTED TESTING METHODOLOGIES/CONTROLLED USE TESTS (25)A. Controlled Dry Skin Kinetic StudiesThe objective in these studies is to demonstrate efficacy of a topically appliedproduct over a short-term period, and may include comparing that efficacywith competitive standards. Examples of claims that positive results from thesestudies may support are \"Moisturizes instantly,\" \"Moisturizes for up to 12hours,\" or \"Superior to the leading moisturizers.\" This is usually accomplishedusing biophysical methods. Twenty to 30 people are typically recruited to par-ticipate as volunteer subjects, but the number of subjects required in any clini-cal trial is determined by the power of a study to detect clinically significantdifferences in treatments (26). Power is an expression of the ability of a studyto detect differences in treatments if one exists, and is dependent on the re-sponse rates of the treatments, the significance level desired, and the numberof subjects treated (26). Therefore, knowledge of the anticipated differencesamong treatments is important so that a sufficient number of subjects can beenrolled to ensure with reasonable certainty that a statistically significant dif-ference will be obtained if the anticipated differences between treatments ex-ist. The error of believing that there is no difference between treatments whenin fact there is, is referred to as a type II or |3 error. Many clients unfortunatelyignore this aspect of clinical trials, because of the higher costs associated withlarger panels. Treatment sites are usually the volar forearm or the lateral aspect of thelower leg. Three to four sites including a no-treatment site can be marked on

Evaluating Conditioning Formulations on Human Skin 359each arm or leg with a marker and the aid of a template. Usually 2 mg of testmaterial are applied per square centimeter for treatment sites. This has beenfound to be an effective quantity of a lotion or a cream to sufficiently coverthe skin surface (27). Bioinstrumentation measurements are taken at baseline,and at intervals after product application up to 48 hr. The intervals selecteddepend on effectiveness times required for a claim. For instance, if one wishesto claim that a moisturizer is effective for up to 6 hr, then the results must showa significant difference in moisturization between the 6-hr time point andbaseline, and the untreated control site. An untreated control is important toinclude, since even several hours can affect skin condition, especially if theenvironmental conditions are changing rapidly. The effectiveness of a mois-turizer or a skin barrier repair agent can be assessed using an evaporimeterto measure transepidermal water loss (TEWL), and a conductance meter tomeasure the relative hydration of the stratum corneum. Both techniques havebeen shown to be effective in quantifying moisturization treatment effects onskin (28), and typically show an inverse relationship. However, the opposite istrue for irritants, which damage the stratum corneum and thus compromiseits integrity (Figure 10). Barrier repair studies require that the starting skin condition be slightly tomoderately compromised. We usually specify that TEWL should be >7 g/m^for the forearm and >12 g/m^ for the lower leg. Likewise for moisturizationstudies, the skin should show moderately dry symptoms.B. Controlled Modified Dry Skin Regression Studies (1)The objective of these studies is to evaluate the efficacy of a moisturizer, usu-ally against a competitive standard, in resolving moderate to severe dry skin.This is accomplished using clinical and bioinstrumentation methods. Approxi-mately 20 to 30 subjects (see Section IILA) with mild to moderate skin drynessare employed per treatment cell. Treatment sites are typically the hands or thelegs, but could be other areas of the body such as the face if that were the targetof the marketing claim or the category of product being tested. The lateralaspect of the lower leg offers an advantage in that it is a uniform, relatively flatsurface allowing bioinstrumentation probes to be easily placed in contact withthe skin, and clinical scaling and cracking are easier to grade on the leg. Testproducts are applied once or twice per day for up to 3 weeks, followed by ano-treatment period (the regression phase). Clinical and bioinstrumentationassessments are typically done at baseline, 2 days, 4 days, 1 week, 2 weeks, and3 weeks during the treatment phase, and every day or every other day duringthe regression phase until the dry skin condition has returned to baselinelevels. Therapeutic moisturizers resolve dry skin more quickly, and they willmaintain good skin condition longer after the discontinuation of treatment

360 Rtz*r Vt al. TEWL VALUES CLINICAL VALUESERYTHEMA EDEMAFIgur* 10 2.0% SLS repeated 6-hr exposures (forearm) chemical irritation. The in-verse is usually true when evaluating the cffea of a therapeutic moisturizer using cva-porimctry to measure TEWL The lower readings reflect the produa's ability to slowwater loss from the stratum corneum by improving the barrier properties of the stratumcorneum. However, the opposite is true for irritants, as illustrated in this example ofrepeated exposure to SLS, which damages the stratum corneum and thus compromisesits integrity. High TEWL readings result from this damage.

Evaluating Conditioning Formulations on Human Skin 361compared to nontherapeutic moisturizers; the regression phase of these stud-ies is thus a good way to differentiate between the two.C. Controlled Product Usage Studies1. Photoaging StudiesThe objective of these studies is to establish the efficacy and safety of one ormore product treatments designed to improve the appearance of photodam-age on the face, upper chest, or backs of the hands. These are the most visibleareas of the body, and the areas that men or women who have suffered theravages of years of unprotected sun exposure want improved. Typical efficacyparameters are improvements in fine lines and wrinkles, sallovraess, tactileroughness, skin laxity, and mottled pigmentation. Usually 30 to 40 subjects(see Section III.A) are required per cell. Volunteer subjects must meet specificselection (inclusion) criteria, which include having moderately photodamagedskin as determined by clinical examination using a grading scale such as theGlogau classification system (29). After subjects are qualified and enrolled inthe clinical trial, they typically undergo a 3- to 7-day \"wash-out\" period duringwhich they discontinue the use of all moisturizers and moisturizing founda-tions. They are permitted to use a mild cleanser, and under some circum-stances are permitted to use a standard light-duty moisturizer, especially if theenvironmental conditions are dry and cold. If the skin is allowed to dry out toomuch, the skin may become compromised and subject to irritation. Many ofthe treatment actives found in \"antiaging\" products are irritants in their ownright. In our experience, applying all trans-Ktinoic acid or an alpha-hydroxyacid to dry, sensitive skin will illicit skin redness and swelling in approximately10-15% of the population of a test panel. Even under normal circumstances,approximately 10-15% of subjects may experience a range of symptoms fromskin redness and scaling to sensations of burning, stinging, tightness, or itching.During the first 2 weeks of product usage, after their skin accommodates tothe irritation, most of the subjects will be able to use the product withoutfurther symptoms. However, the skin of approximately 1-2% of the studypopulation will not accommodate to the irritation, and these subjects will needto be dropped from the study. At baseline, subjects begin using the treatment product assigned, usuallytwice per day for up to 6 months. Clinical assessment of the effectiveness andirritation of the treatment is usually conducted at monthly intervals. Assess-ment of irritation includes erythema (skin redness), edema (skin swelling),scaling (skin dryness), acne breakouts, and the subjective sensations of burning,stinging, itching, tightness, and tingling. Bioinstrumentation methods are oftenemployed to substantiate clinical improvement. These include silicone repli-cas with image analysis for fine lines and wrinkles, D-Squame Disk sampling

362 Rlzer et al.of surface skin cells (squame) to assess desquamation pattern, conductancemeter measurements (e.g., NOVA Dermal Phase Meter or SKI CON Skin Sur-face Hygrometer) to evaluate skin hydration, skin elasticity measurements (e.g.,Cutometer SEM 474 or Ballistometer, Hargens), and colorimeter measure-ments (e.g., Minolta Tri-Stlmulus Colorimeter) to evaluate skin clarity changes.In addition, high-quality clinical documentation photography is sometimesemployed to document clinical improvement (see Section II.C.2).2. Cell Turnover (Stratum Corneum Replacerrient Method)A modest increase in cell turnover is thought to improve the health of the skinby helping to remove dull, skin surface cells (29). Compounds such as reti-noids, alpha-hydroxy acids, and beta-hydroxy acids all have keratolytic activity,and they are commonly used in today's antiaging products because of theireffects on cell turnover, but also because they are beneficial in improving thephotoaging attributes discussed in Section III.C.l. Fluorescent staining of thestratum corneum (SC) with dansyl chloride has been shown to be an effectivemethod for estimating SC replacement time (30). Approximately 18 to 20subjects are used to do pairwise comparisons on the volar forearm (seeSection III.A). This allows one arm to be treated with the test product, andthe contralateral arm to be treated with a placebo control or no treatment.Testing multiple test products requires a balanced block design with additionalsubjects. In this method forearms are occlusively patched with 5% (w/w) dansyl chlo-ride in petrolatum. Patches are removed after 6 hr and repatched with freshdansyl chloride. After 24 hr, patches are removed and sites are gently cleansedwith moist Webril pads and read in the dark for fluorescence using a Woodslight. Subjects then treat their forearms as directed, and return to the clinicafter 1 week to begin having their forearm sites graded for the presence offluorescence. Subjects return every 2 days for grading until both forearms nolonger have fluorescence at both patch sites (fluorescence extinction method).A treatment that produces a significant decrease in SC replacement time com-pared to either an untreated control or a placebo formula as measured by thedisappearance of skin fluorescence is regarded as having a beneficial effect.There are variations in this method that involve treatment with product forone or more weeks followed by fluorescence staining of the SC and furthertreatment. In this case, the skin is preconditioned with the test product.3. Pore Size/Sebum Excretion StudiesThese studies are designed to evaluate the effects of topically applied testproducts to alter either the apparent size of facial pores, or the amount ofsebum being delivered to the skin surface. The pores are the outward appear-ance of the sebaceous follicles, and when they are large and numerous we refer

Evaluating Conditioning Formulations on Kiuman SIdn 363to this condition as \"orange peel skin,\" while too much sebum being deliveredto the skin surface results in greasy, oily skin, a condition called seborrhea. Thesebaceous follicle is always in dynamic equilibrium, producing sebum withinthe gland, storing sebum in the follicular reservoir, and delivering sebum fromthe follicular reservoir onto the skin surface, called sebum excretion. Tonersand clarifying lotions help to keep the skin surface sebum-free, and effectivelyreduce the amount of sebum in the sebaceous follicle. But their action is short-lived, since sebogenesis is a powerful process, and the follicular reservoir canrefill and begin spewing sebum onto the skin surface within a few hours. Studies designed to evaluate either the effects of test products on pore sizeor skin surface sebum typically incorporate a combination of clinical, photo-graphic, and biophysical methods. At baseline, volunteer subjects are qualifiedby having their foreheads or cheeks cleansed with a mild liquid cleanser, de-fatted with hexane, and wear Sebutape patches (31) for 30 or 45 min to collectsebum. Sebutape samples from each individual are graded against a referencestandard for low, medium, or high sebum levels. Individuals with medium orhigh levels are usually selected for enrollment. The Sebutape samples fromqualified subjects are carefully placed on view cards, and stored in the freezerunder nitrogen gas until analyzed. Subjects are also clinically evaluated forpore size and the degree of impacted material (keratin plug) within the follicle.High-quality color macrophotos are also taken for documentation, and forsubsequent image analysis of pore size. Sometimes more than one baselineprocedure is done for averaging, in order to reduce the inherent biologicalvariability in sebaceous gland activity within the population. Factors such asage, gender, and endocrine status of prospective subjects may affect the meas-urement. For instance, oral contraceptives decrease sebum excretion rate(SER), whereas the effect of the menstrual cycle is of minor importance (32).However, a 1°C change in skin temperature produces a 10% change in SER(33), and SER is highest in the morning and lowest during the late eveningand early morning hours (34). Consequently, control of these variables willbenefit the outcome of these studies. Test products are administered to the study population for use accordingto label instructions for varying periods of time, depending on the nature ofthe product. Some products may have an immediate effect on the appearanceof pores, but products designed to affect sebogenesis usually require weeks tomonths of treatment. A variety of techniques are available for estimating SER.Our method of choice is the Sebutape patch method, which is a lipid-absorbenttape technique (31,35). Other methods include the time-proven gravimetricabsorbent paper technique of Strauss and Pochi (36), and the cup techniqueof Ruggieri et al. (37). A photometric method developed by Schaefer inEurope is based on the reduction in optical density of ground glass in contactwith fat (38).

364 Rlzer et al.IV. CONCLUSION AND FUTURE DEVELOPMENTSAs Dr. Albert Kligman (39) has suggested in the introductory chapter of theHandbook of Non-Invasive Methods and the Skin, \"the future is already here\"and those at the cutting edge of a discipline that promises to deliver new andimproved noninvasive instruments for skin evaluation are like \"a rich child ina Viennese pastry shop.\" As the personal microcomputer (PC) has become smaller and more pow-erful, the instruments already in use in the clinical laboratory are becoming\"smarter.\" In the area of clinical documentation photography, the digital erahas arrived. Crisp color photos can be archived to CD-ROM disks, providingcompact storage accessible to any modem PC with a CD-ROM reader andmuch more permanent than any print or negative. New smarter instrumentswill warn the operator of environmental conditions likely to confuse its \"sen-sors.\" Instruments will \"talk\" directly to other computers in the laboratory,logging data automatically. Client-server on-line acquisition of instrumenta-tion data in the clinical setting has already been implemented (40). All dataincluding questionnaire and evaluator scores are integrated in a relationaldatabase system which ties in subject identification, treatment schedule, etc.The system can automatically apply quality assurance rules to entered data, aswell as secure data logging. More precise and sensitive instruments for visualizing specialized aspectsof the skin are on the horizon. These include more advanced spectroscopytechniques that will allow noninvasive determination of the spatial distributionof collagen and keratin fibers as well as other optically reactive substances invarious layers of the skin (41). Magnetic resonance imaging (MRI) of the skin is coming of age with therecent announcement of portable units for obtaining this valuable data (42).Skin MRI promises to noninvasively generate well-resolved images of suchthings as the actual water profile of the skin, the pilo-sebaceous unit, and otherappendages and features of the dermis (39). All of these emerging technologies will not be able to stand alone, but theywill provide much stronger complementary support to clinical and subjectiveassessments of skin conditioning. The integrated approach, as we have illus-trated in this chapter, will stand the test of time, and it will be the best approachfor supporting credible marketing claims of product performance benefit. Forfurther information, the reader is referred to Refs. 43-46.ACKNOWLEDGMENTSSpecial thanks are given to Robert Goodman, Professional Photographer,Dallas, TX, for assistance with clinical photodocumentation procedures, and

Evaluating Conditioning Formulations on Human Skin 365to Andrew Lawson, Ph.D., Lawson and Associates, Austin, TX, for assistancewith Section ILF, \"Statistically Based Conclusions.\"REFERENCES 1. Kligman AM. Regression method for assaying the effectiveness of moisturizers. Cosmet Toilet 1978; 93:27. 2. Seitz JC, Rizer RL, Spencer TS. Photographic standardization of dry skin. J Soc Cosmet Chem 1984; 35:423-437. 3. Goldschmidt H, Kligman AM. Exfoliative cytology of human horney layer. Arch Dermatol 1967; 96:572. 4. Prall JK, Theiler RF, Bowser PA, Walsh M. The effectiveness of cosmetic products in alleviating a range of dryness conditions as determined by clinical and instru- mental techniques. Int J Cosmet Sci 1986; 8:159. 5. Schatz H, Kligman AM, Manning C, Stoudemayer T. Quantification of dry (xero- tic) skin by image analysis of scales removed by adhesive discs D-SQUAME®. J Soc Cosmet Chem 1993; 44:53-63. 6. Philp NJ, Carter NJ, Lenn CP. Improved optical discrimination of skin with polar- ized light. J Soc Cosmet Chem 1988; 39:121. 7. Cook TH. Profilometry of the skin—a useful tool for the substantiation of mois- turizers. J Soc Cosmet Chem 1980; 31:339. 8. Grove GL, Grove ML, Leyde JJ. Optical profilometry: an objective method for quantification of facial wrinkles. J Am Acad Dermatol 1989; 21:632. 9. Welzel J, Wolff HH. Laser profilometry. In: Berardesca E, et al, eds. Bioengineer- ing of the Skin: Skin Surface Imaging and Analysis. Boca Raton, FL: CRC Press, 1996:part IIB.10. Distante F, Berardesca E. Hydation. In: Berardesca E, et al, eds. Bioengineering of the Skin: Methods and Instrumentation. Boca Raton, FL: CRC Press, 1995: chap. 2.11. Leveque JL DeRegal J. Impedance methods for studying skin moisturization. J Soc Cosmet Chem 1983; 34:419.12. Serup J, Jemec GBE, eds. Handbook of Non-Invasive Methods and the Skin. Boca Raton, FL: CRC Press, 1995.13. Berardesca E, et al, eds. Bioengineering of the Skin: Methods and Instrumenta- tion. Boca Raton, FL: CRC Press, 1995.14. Jackson EM, Stephens TJ, Goldner R. The use of diabetic panels and patients to test the healing properties of a new skin protectant cream and lotion. Cosmet Dermatol 1994; 7:44-48.15. Rizer RL, Stephens TJ, Jackson EM. A comparison of the irritant contact derma- titis potential of various cloth and plastic wound bandages on sensitive skin indi- viduals. Cosmetic Dermatol 1994; 7:50.16. Stephens TJ, Oresajo C. Ethnic sensitive skin. Cosmet Toilet 1994; 109:75-80.17. Pinnagoda J, Tupker RA, Agner T, Serup J. Guidelines for transepidermal water loss (TEWL) measurement. Contact Derm 1990; 22:164.18. Hargens CW. Ballistometiy. In: Serup J, Jemec GBE, eds. Non-Invasive Methods and the Skin. Boca Raton, FL: CRC Press, 1995: chap. 14.8.

366 Rizer et al.19. Fthenakis CG, Maes DH, Smith WP. In vivo assessment of skin elasticity using ballistometry. J Soc Cosmet Chem 1991; 42:211-222.20. Cua AB, Wilhelm K-P, Maibach HI. Elastic properties of human skin: relation to age, sex, and anatomical region. Arch Dermatol Res 1990; 282:283-288.21. Dorogi PL, Jackson EM. In vivo video microscopy of human skin using polarized light. J Toxicol—Cut & Ocular Toxicol 1994; 13:97-107.22. FuUerton A, Fischer T, Lahti A, Wilhelm K-P, Takiwaki H, Serup J. Guidelines for the measurement of skin color and erythema. Contact Derm 1996; 35:1-10.23. Miller DL. D-SQUAME® adhesive disks. In: Wilhelm K-P, et al, eds. Bioengineer- ing of the Skin: Skin Surface Imaging and Analysis, Boca Raton, FL: CRC Press, 1996: part IIA, chap. 2.24. Miller DL. Application of objective skin type kits in research and marketing. In: Cosmetics and Toiletries Manufacture World Wide (1996 Annual). Herfordshire: Aston Publishing, 1996:233.25. Jackson Em, Robillard NF. The controlled use test in a cosmetic product safety substantiation program. J Toxicol-Cutaneous & Ocular Toxicol 1982; 1:117-132.26. Bigby M, Gadenne A-S. Understanding and evaluating clinical trials. J Am Acad Dermatol 1996; 34:555-594.27. 21 CFR Part 352. Sunscreen drug products for over the counter human use; ten- tative final monograph. Fed Reg, May 12,1993; 58:29299.28. Serup J. A double-blind comparison of two creams containing urea as active in- gredient. Acta Derm Venereol (Stockh), suppl 1992; 177:34-38..29. Glogau RG. Chemical face peels. Dermatol Clin 1991; 9:131-150.30. Jansen LH, Hojyo-Tomoko MT, Kligman AM. Improved fluorescent staining technique for estimating turnover of the human stratum corneum. Br J Dermatol 1974; 90:9-12.31. Nordstrum KM, Schmus HG, McGinley KJ, Leyden JJ. Measurement of sebum output using a lipid absorbent tape. J Invest Dermatol 1986; 87:260-263.32. Cunliffe WJ, Cotterill JA. In: The Acnes: Clinical Features, Pathogenesis and Treatment. London: WB Saunders, 1975.33. Cunliffe WJ, Burton JL, Shuster S. Effect of local temperature variation on the sebum excretion. Br J Dermatol 1970; 83:650.34. Burton JL, Cunliffe WJ, Shuster S. Circadian rhythm in sebum excretion. Br J Dermatol 1970; 82:497.35. Pidrard GE, Pi6rard-Franchimont C, LS T. Patterns of follicular sebum excretion during lifetime. Arch Dermatol Res 1987; 279:S104-S107.36. Strauss JS, Pochi PE. The quantitative determination of sebum production. J In- vest Dermatol 1961; 36:293.37. Ruggieri MR, McGinley KJ, Leyden JJ. Reproducibility and precision in the quan- titation of skin surface lipid by TLC. In: Touchstone JC, ed. Advances in Thin- Layer Chromatography. New York: Wiley, 1982:249-259.38. Schaefer H. The quantitative differentiation of the sebum excretion using physical methods. J Soc Cosmet Chem 1973; 24:331.39. Kligman AM. Perspectives on bioengineering and the skin. In: Serup J, Jemec GBE, eds. Handbook of Non-Invasive Methods and the Skin. Boca Raton, FL: CRC Press, 1995: chap. 1.1.

Evaluating Conditioning Formulations on IHuman Sidn 36740. Wilhelm K-P. Client-server based on-line data acquisition for skin bioinstrumen- tation (presentation abstract). Skin ResTechnol 1996; 2:201.41. Utz SR. In vivo human skin spectroscopy: prelude to optical tomography (presen- tation abstract). Skin Res Technol 1996; 2:201.42. Zemtsov A. Personal communication (DLM), 1997.43. Merker PC. Good laboratory practices (GLP's) and good clinical practices (GCP's): beneficial impact on safety testing. J Toxicol 1984; 3:83-92.44. Larsen WG, Jackson EM, BArker MO, et al. A primer on cosmetics. J Am Acad Dermatol 1992; 27:469-484.45. Friedel SL. Technical support for advertising claims. J Toxicol—Cut & Ocular Toxicol 1992; 11:199-204.46. Spilker B. Guide to Clinical Trials. New York: Raven Press, 1991.

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IndexAcetyl cysteine, 160 [Alcohol {see also Fatty alcohols)]Acid mantle of skin, 4,240 as moisturizing ingredient, 18,26,Acne, 85, 86,160,162,341,345,361 27,80,96,97,101,103,106,Acrylamide/b-methacryloxyethyltri- 119-123,127-133,135,264,302 in skin structure, 18,119 methyl ammonium methosul- fate {see Polyquaternium 5) Alkanolamine, 210Acrylic copolymer latex, 276 Alkylamido betaine, 224ACS {see American Chemical Society) Alkylamines, 228,229,244Active ingredient, 80,83,125,175, Allq^l betaine, 224 Allq'l dimethicone copolyol, 206 244,263,276,295,340 All^l functional siloxane, 179Active species, 230,252 Allq^l imidazolines, 228,230Acylceramides, 43,46 {see also AHQfl methyl siloxane, 179,185,196 Alkyl quaternary protein hydrolyzates, Ceramides)Addition polymerization, 252 157Adipic acid/dimethylaminohydroxy- Allergenicity, 86,144,162 Alpha-hydroxy acids, 72,244,340,362 propyl/diethylenetriamine co- Aluminum, 61,103,186,245,320 polymer, 264 Aluminum acetate, 245Adsorption, 153,199,235,237, American Chemical Society, 169,196, 256-258, 309, 319,320,322, 333 293Aftershave, 159,258 Amidoamine salt, 240,242AHA {see Alpha-hydro)Q' acids) Amidoamines, 226Alcohol {see also Fatty alcohols) Amine oxides, 225,226,295 as humectant, 96,97,100,101, Amine salts, 229,234 103 369

370 IndexAmino acids, 139-141,148,150-152, Astringents, 27,125,258 154,156,159,162,165 Atopic dermatitis, 25,43,48, 86,341 Azelaic acid, 265 as additives in conditioning products, 143,147,158,160,161,162,254 Ballistometer, 350,352,362 Barrier disruption, 14,17,18, 25,26, in hair structure, 23 in proteins, 144-146,154,156,159 29,35,37,39-41,46-49,57,73, in slcin structure, 16 80 synthesis, 141 Banier repair, 25,46,359 Bar soap, 241 use in hair care, 143,147,254 Baseline 343,353,356,359,361,363 use in slcin care, 158,160,161 Bases, 100,120,188,191,233,238,Aminoethyl acrylate phosphate/acrylic 251,322 Benzalkonium chloride, 227 acid copolymer, 276 Bephenyltrimethylammonium chlo-Amino-functional siloxane, 188,190- ride, 316 Beta-hydroxy acids, 340,362 192,194 Betaine, 107,224,225,228,240,244,Amino group, 139-141,208,231 245Amodimethicone, 180,189,208,209, Biodegradability, 161,287 Biological membranes, 244 273,274 Biomimetic lipids, 282Amphiphatic peptides, 245 Biophysical methods, 339, 345,358,Amphoacetates, 224 363Amphoteric, 139,240,242 Biosynthetic polymer, 251 Biotechnology, 161 derivatives, 230 Bleaching of hair, 29,143,153,155, surfactants, 211,223-225, 228,244, 234,237,241,263,301,307,308, 318,319 253,254,257,263-267,304 Block polymers, 266 use in hair care, 231,234, 266,267, Botanical extracts, 162 Bovine Spongiform Encephalopathy, 276 161AMS (see Alkyl methyl siloxane) Bricks-and-mortar model of the stra-Anagen phase of hair growth, 20 (see tum corneum, 36 (see also Stra- tum comeum) also Hair, growth cycle) BSE (see Bovine Spongiform Enceph-Anion, 224,252,265 alopathy)Anionic compatible, 225,241 Buildup, 251,253,255,257,258,261,Anionic dyes (see Rubine dye) 302,303,313Anionic surfactant, 159,225,240,255, of conditioners, 316,318,326,327, 331,332 256, 266,267,320 hair conditioning, 265-267,282,304,Antiaging, 361,362 304,307,319,320,322,323,Anticalculus agents, 245 325Antidandruff shampoos, 263Antigenicity, 161Anti-inflammatory, 3,48,49,158,340, 345Antimicrobial 102,103,245,297Antistatic agent, 237Antistatic properties, 195,210,211, 214,216,229,267,276Ascorbic acid, 162Asparagine, 140,147,149,151-153Aspartic acid, 140,147,153,156

Index 371[Buildup] Cholesteryl betainate, 244 and polymers, 253-255,257,258, Claims 262,264,265,267-269,276,277, 284,308 humectants, 105,106 and quats, 213,238,242 label, 4,9,63,175 properties, 237,241,254-256,264, petrolatum, 79,81,85 277,284 product, 283,287,290,291,304,332, skin conditioning, 258 and silicones, 187,190,191,211, 338-340,343,358,364 273,274 quats, 241,243 of static, 6 substantiation, 344,345 Clear products, 188,190,193-195,Cady, L. D„ 14Capacitance, 338,345 210,241,242,273,274Capric/caprylic esters, 114,134,135 Clinical assessment, 339,343,361Carbomer, 182,217 Clinical documentation photography,Carboxyl group, 139Cation, 178,252,259,263,264,325 343,344,364Cationic polyelectrolytes, 265,333 Clinical studiesCationic polysaccharides, 241Cationic surfactant, 10,209,223-245, of hair, 238,295-296 of skin, 72,295-296,338,345,353,359 254,256,274,276,302,303,320, Clinical testing, 295,296 325 Clinical trial, 340,361Cellular turnover, 14,362 Cloudpoint, 107,193,243Ceramides, 18,38,39,40,41,43^6, CMC (see Critical micelle concentra- 282 (see also Acylceramides, Glucosylceramides) tion)CETAC (see Cetyltrimonium chloride) Cocamidopropyl betaine, 107,228Cetyl alcohol, 26,128,182,191,192 Cocodimonium hydrolyzed soy pro-Cetyltrimonium chloride, 214,215CFR, 164,197,215,218 tein, 272Chafing of skin, 81 Cocodimonium hydroxypropyl hydro-Chain interaction 253Chain-reaction polymerization, 252 lyzed keratin, 271Chapped lips, 344 Cold cream, 112,183Chapped skin, 175,341 Collagen, 143-146,148-151,153-161,Charge distribution, 263,323Charge properties, 236 164,234,283Chemical treatments, 301,302,307, as an additive in conditioning prod- 319Chesebrough, 59-62, 87 ucts, 105,107,143,144,154,271Chitosan acetate, 321 amino acid profile of, 150Chlorosilane monomers, 168 in skin structure, 15-19,140,153,Cholesterol, 4,41,44,46Cholesterol sulfate, 18,38 161 synthesis, 141 Collagen hydrolyzates, 143,156 Colloid, 24,62,180,313 films, 146,154,159 Colloid polymer titration, 304 Cologne, 258 Color (see also Oxidative color. Bleach- ing of hair) of formulations, 83,288,297,327 of hair, 4,5,143,154,157,204,238, 318

372 Index[Color] [Conditioning] of ingredients, 59,101,133,143-145, mechanisms of, 28 154,156,173,242,283 products, design of, 7-9 loss in hair due to exposure to ultra- relationship to structural factors, 2, violet light, 29 17,20 of skin, 4,160,243 of skin, 13,69,79-87, 111, 158-161, 277,337-345,353,359,Colored hair, 204,311,312Color image processor, 312 Conditioning shampoo, 188,192-194,Colorimeter, 352,362 199,227,274Combing, 192,205,210,214,235-238, Condition of skin, 5,6,10,112 256,263,274,276,284,286,324, Conductivity, 2,6,7,236,237,313, 331 (see also Detangling) 314,316,318,321-323 as a cause of damage, 2,27,301 Conformation stability of proteins, 146 properties, 6,158,187,215,274,295 Connective tissue, 15,16,18,140,142, and static charge, 28,82,236,240 test procedures, 304 -310 154 ofwet hair, 24,191,255 Consumer testing, 296,297,326,327,Combing analysis, 304,307Combing curve, 305,307,324 332Combing force, 187,195,237,305, Contact angles, 319 Coordination complex, 252 307,323 Copolymer, 180,184,252,259,261-264,Combs, 323,324Comedogenicity, 85,86,218 268.269.275.276Compatibility, 130,240,241,283 Copolymerization, 252 Corneocytes, 17,24,25,35,36,38,40, vi'ith anionics, 157,214,225,227,242, 253,263,265,270 337,352 Cortex, 2,3, 21,24,28,143,153,161, with hydrocarbons, 100,130 of polymers, 263,265,269,270,272 302 of proteins, 144 Cosmeceutical, 158 of quats, 227,228,238 Cosmetic interactions, 340 of silicones, 173,176,178,179,181, Cost parameters, 287,294 Coulombic attraction, 256,266 192,208, 210,214,273 Creme rinses, 227,263,265,271Competitive claims, 332 Critical micelle concentration, 159,Computerized image analysis, 338Computers, 293,323,332,352,364 263,267Condensation polymerization, 252 Crosslinked polymers, 171,180,195,Conditioning, 1-7,57,95, 111, 332 258.265.273.277 effects of cationics, 251,253,254-277 Curl retention, 191,195,198,217,266, effects of proteins, 153,157,234, effects of siUcones, 175,179-195,202, 269,276 Cuticle 204, 206-212,282-297, evaluation of properties, 304-327 damage of, 2,5,238,301,302,311, of hair, 14,23,24,25-29,58,147,219, 325 227,229,238,241-244,301-308 improvement of, 143,153,161,189 and humectants, 95,99,108 as part of hair structure, 2,3,5,21, of leather, 62 27 Cutometer SEM, 352,362 Cyclomethicone, 167,173,176,178, 182-185,189,200,206

Index 373Cyclotrisiloxane, 172 [Dimethicone]C^steic acid, 145,149,155,162 formulation considerations, 181,185,Cysteine, 17,140,145,155,156,160, 192.282 as an OTC drug ingredient for skin 301 protection, 175Cytokines, 25,47,48,162 structure, 167,174 use in hair conditioners, 185,188,Danfortli, C. H., 14 262.283Dansyl chloride, 362 use in skin conditioners, 176,282,Data analysis, 303,326,353DDAC, 262 Dimethicone copolyol, 189,190,194,DDAC/acrylamide, 263 198,205,206,209,210,214,DDAC/acrylic acid, 263 217-221,275Defoamers, 175Defoaming of silicone 202 Dimethicone copolyol amine, 209Denaturation of protein, 17,140,158 Dimethicone copolyol cocoabuterate,Dental caries, 245Deoxyribonucleic acid (DNA), 45-47 219DEPA, 313,314,316,318 Dimethicone propyl PG betaine, 245Dermatitis, 25,29,43,48,70,80,86, Dimethiconol, 174,182-184,189,194, 341 204,213,218,220Dermatology, 13,14,70,75, 86 Dimethiconol fluoroalcohol dilinoleate,Dermis, 15,16,19,26,44, 48,364Descriptive analysis panel, 327 220Desmosine, 148,154 Dimethiconol stearate, 220Desmosomes, 15 Dimethyl diallyl ammonium chloride,Desorption, 235,303,313,318,333, 262 345 Dioctyl phthallate, 133Desquamation, 7,16-18,24,29,37, Dipalmitoylethylhydroxyethylmonium 40-42,337,352,362 methosulfate, 234Detangling properties, 188-190,214, Disodium cocoamphodiacetate, 231 Disodium lauroamphodiacetate, 231 238,257,263,295,301,332 {see Distearyldimonium chloride, 238 also Combing) Disulfide bonds, 156,162Detergent, 134,144,199,217,257,267 DMAEM, 260Diastron, 296,304,309 (see also In- DMDM hydantoin, 145 stron. Tensile strength measure- DOPA, 243 ments) Dow Corning Corporation, 173,197,Diazolidinyl urea, 145Dichlorodimethyl silane, 168 198Dihydroxy phenylalanine, 243 Drug interactions, 340Dilution deposit, 255,257,263,269, Dryness of hair and skin, 5,8,29,72, 272,273Dimethicone, 76,167,174-176,178, 73,285,338,343,344,359,361 181,198,204-207,209,210, D-SQUAME adhesive disks, 352 212-214,217-221,275 (see also Dynamic electrokinetic and permeabil- Silicone, Polydimethylsiloxane) ity analysis, 313 Eccrine glands, 18 Edema, 343,344,361 Eicosapentaenoic acid, 118

374 IndexElastase, 161 Exocuticle, 21Elastin, 140,142,148-151,154,159 Exothermic conditioner, 214Electrical measurement of skin, 338, Experimental design, 353,356 Expert panel, 325-327 339,345 Eye irritants, 209Electrometer, 320,324 Eye irritation, 105,179,189,190,215,Electron spectroscopy, 304,333Electrophoresis, 141 218,254,259Elias, P., 35,36,40,42,44,46,48Emollient, 27,62,70,73,76,103,104, Facial lotion, 340 Facialwashes, 160,181 111-113,115,117,119-121, False claim, 340 123-125,129,131,133,135,175, Fats and oils (see also Triglycerides) 198,251,258,264,267Emulsifiers, 82,159,178,179,182, carbon chain distribution of, 117 183,196,197,207,216,217,229, defmitionof, 114,117 234,240,244,246 hydrolysis of, 96,101Emulsion, 73,78,85,99,107,115,124, as moisturizing agents, 26,117 130,147,161,182,183,188-192, solubility, 99 197,204,208,209,217,219,234, Fatty acid, 18,39,41-47,70,112, 240,273,274,316 formulation considerations, 83,100, 114-119,122-125,127,129-131, 120,141,154,158,160,178, 135,144,157,160,173,195,218, hair applications, 58,82,188,189 230,245,254,272 skin applications, 72,78,115 Fatty acid chloride, 144,157Endocuticle, 21 Fatty alcohols, 26,106,127-131,224Endotoxins, 163 as emollients, 27Enzymatic activity, 36,140,141,146,147 as occlusive agents, 26Enzymes, 37-41,45-46,81,144,146, Fatty alkyl-substituted amines, 224 154,158,161-163 Fatty quaternary compounds, 213,215EPA, 118,173 FDA, 80,214Epichlorohydrin, 270 Fiber adhesion index, 309Epidermal keratocytes, 161 Fiber conductivity, 321,322Epidermal lamellar body, 36,37,39 Fiber elongation, 237Epidermis, 15,25,44,45,48 Fibrinogen, 1402,3-Epoxypropylamine, 264 Fibroblast, 161,245Erythema, 343,344,361 Fibrous proteins, 140Esca, 268,304,333 Film-forming properties, 28,129,176,Ethnic populations, 341 181,198,257,262,275Ethoxylated amines, 228,231,233 Films, 73,95,133,159,170,180,181,Ethoxylated quaternaries, 238 187,259,263,270,275EthojQflated surfactants, 263 Fine hair, 28,316,326Ethylene diamine, 179, 232 Fine lines, 153,337,339,340,343,344,Ethylene glycol, 100,134 353,361Ethylene oxide, 100,108,129,130, Flow rate, 316,326 178,217,232 Fluorescence microscopy, 325Eutectic point, 129 Flyaway, 6,82,187,188,238,254,265,ExfoUiant, 8,48,158 267,270,274,284,286,321 (see also Static charge)

Index 375Foam boosters, 154,183,217 Goniophotometric techniques, 310Foam stabilizer, 154 Gram-negative bacteria, 163Focus group, 341,342 Greasiness, 81,82, 85,131,173,176,Follicle, 14,19,20,28,363Formaldehyde, 145,158 186,283Formula within a formula, 285 Guar gum, 195,211,241,253,256,270Formulation process, 285,287,294, Guar hydroxypropyltrimonium chlo- 295 ride, 255,270,309Fragrance, 99,102,103,145,164,286, Guerbet alcohols, 132 Gum, 168,182,184,189,195,241,253, 294,297,331Fragrancing, 302,326 256,270,283,300Free radical, 252Friction, 7,23,24,80,171,190,305, Hair appearance of, 4 307 body, 266,309,310,332Functional benefits, 193,286,287 compositional elements, 3, 21,140,Functional groups, 211,212,224,243, 149,154 curl, 23 251-253,255 damage, 2,27,154,190,301Functional ingredients, 238 elasticity of, 24,153,155 growth, 14,19,21Gaucher disease, 41 instrumental methods of evaluation,Gelatin, 26,141-143,150,151,153, 304-325 moisturization, 99,108,284,285 154,156,158-160,163,165,271 physical properties, 6,24,28Gel filtration, 141 shine, 310Gels, 58,107,178,179,186,214,217, straightening, 82 strength, 6,28,308 262,272,273,276,302,312 structure of, 3,4,19-21,23,155 {seeGlass transition temperature, 171,176 also Cuticle, Cortex)Globular proteins, 140 water absorption of, 24,319Gloss {see Shine)Glucosylceramides, 37,41 (see also Hair body, 266,309,310,332 Hair gloss, 310 Ceramides) Hair luster, 141,310,311Glutamic acid, 140,147,153,156 Hair morphology, 310Glutamine, 40,140,147,149,151-153 Hairspray, 157,186,259Glycerin, 10,26,96-107,119,135,182, plasticizer, 158 189 resin, 179,206,312Glycidyl epoxide, 210 Hair types, 326Glycine, 16,140,141,148,150,152, Hexamethyldisiloxane, 169,176 HLB, 134,178,181,193,208, 209, 220 160 Home-use consumer testing {see Con-Glycol, 10,26,27,96-100,102-104, sumer testing) 106,107,134,184,209,220,241, Homopolymer, 259,262,264,271 270 Hormones, 44,162Glycolic acid, 160 Humectancy, 97,98,100,104,144,Glycoprotein, 163Glycosaminoglycan, 15,18,277 146,156,186Glycosphingolipids, 38Gogau classification system, 361Goniometer, 296

376 IndexHumectant, 26, 96-100,102,104-106, Hydroxypropyltrimonium hydrolyzed 108,144,146,156,186,270 (see wheat protein, 272 also Hygroscopicity) Hydroxypropyltrimonium vegetableHyaluronic acid, 4,16,26,268,277 protein, 271Hydrocarbons, 62,63,66,72,73,86, Hygroscopicity, 95,97,98,100,101, 176,179,202,204,303 103-106,146 (see also Humec-Hydrogen peroxide, 226 tancy)Hydrogenated soyadimoniumhy- Idson, B., 5,8,11,70, 111, 252,254, droxypropyl polyglucose, 272 258,262,264,266,270,272,276,Hydrolysis 277,300 of collagen 105,153-154,234,271 Image analysis, 5,11,310,312,333, of elastin, 155 338,352,353,361,363 by enzymes, 38,40 of esters, 121,125,127,128,130 Imidazolidinyl urea, 145 offatsandoils, 101,112,302 Imidazolines, 224,228,230,242,262, of gelatin, 154 of glucosylceramides, 38 266 of hair components, 155,217 In vitro evaluation, 238 of imidazolines, 230 INCI, 143,155,172,174,179,180, ofkeratin, 155,217 of polymers, 264,271 270,273 of protein, 28,105,141-147,149,155- Indoles, 243 Ingredient substantivity, 238 162 (see Protein, hydrolyzates) Instron, 296 (see also Tensile strength of silicone compounds, 168,275 of skin components, 39,40 testing, Diastron)Hydrolyzed collagen, 144,145, Intercellular lipids, 18,25,29,36,37 153-155,157,159,160,164,271 (see also Lipids)Hydrolyzed elastin, 142,154,159 Internet, 293,300Hydrolyzed oat protein, 149,156,164 Ionic interactions, 203,208Hydrolyzed sweet almond protein, 155 Irritation rating, 157,160Hydrolyzed wheat protein, 155,161, Isodesmosine, 148,154 Isoelectric point, 224,235,255 272,275 Isoionic points, 147,153,156,160,272Hydrolyzed wheat protein polysilox- Isopropyl myristate, 27,122,123,128, ane copolymer, 275 130Hydrolyzed wheat starch, 155 Isostearamidopropyl quaternary am-Hydrophile-lipophile balance, 134,178, monium compounds, 241 181,193,208,209,220 (see HLB) Isostearyl derivatives, 242Hydrosilyation, 205,207 Itching sensation, 6,341,343,344,361Hydroxyethylcellulose, 266,268HydroJOfethylcellulose/diallyldimethyl (see also Pruritis) lUPAC, 169 aminonium chloride, 268Hydroxyethyl-ethylenediamine, 245 Journal of the Society of CosmeticHydroxylpropyl methylcellulose, 188 Chemists, 293Hydroxyproline, 16,143,150Hydroxypropyl trimethyl ammonium Keratin hydrolyzates, 154 Keratinocyte growth, 245 chloride ether of, 266 Kinky hair, 23,24

Index 377Kligman, A., 164,300 Melanin, 15,29,243,311Kolliker,A.V, 14 Methyl chloride, 168,224 Methyl[chloro] iso±iazolinone, 145The Lancet, 293 Methylene blue, 303Langerhans, 15,48 Methylene iodide, 319Laser diffraction method, 319 Micellar vesicleSj 163Lauramidopropyl betaine, 244,245 Microbiological preservation, 144Lauryldimoniumhydroxypropyl hydro- Microemulsion, 219,318 Microscope, 66,319,325 lyzed soy protein, 272 Milk protein, 141Lauryl methyl gluceth 10 hy- Mineral oil, 66,80,120,127,173,175, droxypropyldimonium, 234 202,220Leave-in product, 153-156,180,192Leave-on product, 283 distillation of, 112Light-scattering curve, 310,311 structure of, 63,Linear PDMS, 175,176,178,192, use in hair conditioners use in skin conditioners 26,71,73,76, 193Linoleamidopropyl pg-dimonium chlo- 77,106, Moisture binding of humectants, 104 ride phosphate, 244 Moisture retention, 155,238Linoleic acid, 18,41,45 Moisturizing agents, 8,16,27,283Linoleylamidopropyldimethylamine, Molecular weight, 28 217 esters, 124-127,129,131-136Lipase, 37,41,42 polymer, 238,253,256,261-263,266Lipids (see also Intercellular lipids) protein, 139,143,144,146,153,154, as moisturizing ingredients, 112,140, 159 268 silicone, 171,176,178,186-188,202, sequestration of, 36 206,275 in skin structure, 17,18,37-40,42-49, Monochlorotrimethyl silane, 168 Monomers, 139,144,159,168,252, 272,282 stripping of, 18 259,304 synthesis of, 25,42 Mousse, 189,206Lipoamino acids, 160 MRI (see Magnetic resonance imag-Liposomes, 163,282,300Liquid scintillation counting, 258 ing)Load cell, 309,323 Multicomponent systems, 303,320Lysine, 140,148,150,152,160 Multifaceted benefits, 340 Multiple emulsions, 244Macroemulsion, 194 Multiple formulation strategies, 296Magnesium ascorbyl phosphate, 162 Multiple groups, 342Magnetic resonance imaging, 364 Multipronged approach, 339,340Maillard reaction, 145 Myosin, 140Marketing, 8,161,163,275,287,294, Myristamidopropyldimethylamine, 211 300,325,359,364 Nail care products, 9,271Marketing research, 325 Natural gum, 283Mechanical measurements, 308,332 Natural Moisturizing Factor, 16,104Medulla, 21,28 (see also Hair, struc- Natural polymer, 251 ture of)

378 IndexNitrogen derivatives, 238,245 Penetration of ingredientsNMF {see Natural Moisturizing Fac- into hair, 143,153,155,156,194,204, 254,325 tor) into skin, 72,81,86,125,129,160,161,Noncationic polymers, 251,254,258, 245 {see also Percuteaneous ab- sorption) 275,277Noninstrumental analysis of hair, Peptide, 139,141,165 Peptide bonds, 139 325 Percutaneous absorption, 17 {see alsoNonirritating sunscreen, 243Nonocclusive ingredients, 125,146, Penetration of ingredients into skin) 219,220, 275 Permanent wave applications, 186Nova dermal phase meter, 345 PetrolatumNylon, 77,320,321 as a blister preventative, 81 composition of, 57,60,62-66O'Lenick, A. J., 221,243,246 derivation of, 57,59,66-69Occlusive agents, 8,10,26,57,69,73, formulation considerations, 58, 83-85 77-79,125,133,146,179,219, as a medical ingredient, 78-81 283 noncosmetic applications, 61-62Octyl acrylamide-acrylic acid-butylami- as an occlusive agent, 10,26, noethyl methacrylate copoly- resistance to rancidity, 60 mer, 276 safety of, 85-87Oleic acid, 113,114,117,123,220 and transepidermal water loss, 57Oligomer, 243 use in hair products, 58,82-83Oligosaccharide, 155 use in skin products, 26,57,58,01iveoil,59,71,96,114,115 69-78,81Optical microscopy, 319, 325 Petroleum jelly {see Petrolatum)Oral care, 245 PHOrgano-siloxane polymers, 167,168, effect on proteins, 139,140,147,154, 170,187 {see also Silicones) 158Over-the-counter drug, 175 effect on sorbitol chelation, 103 of hair, 235Palmitic acid, 41 and isoionic point, 141,156,235Palmitoyl hydrolyzed wheat protein, of relaxers, 58 ofskin,4,41,240 161 and substantivity, 144,157,208Panelists, 72,176,312,326,327,332, Pharmaceutical preparations, 97,244 Phenoxyethanol, 145 340-342 Phenyltrimethicone, 179,189Panelist selection, 340 Phospholipids {see Lipids)Panelists' perception, 341 Photoaging, 361,362Papain, 158 Photodamage, 337,343,345,353,361Parabens, 145 Photodamaged skin, 337,338Para-dialkyl amino benzamide, 243 Photographic analysis, 338,343-345,Paraffin, 26,57,63,66,73,303 352,362-364Paraffin jelly {see Petrolatum)PDMS {see Polydimethylsiloxane)PEG-2 cocomonium chloride, 238PEG-2 stearmonium chloride, 238PEG tallow polyamine, 276

Index 379Photographic spot meter, 313 Polyquaternium-11,258,267,269Photometric method, 363 Polyquaternium-16,262Photoprotection, 28 Polyquaternium-18,265Physicochemical description, 333 Polyquaternium-19,258, 264Physiological effects, 245 Polyquaternium-20,264Piezoelectric effect, 320 Polyquaternium-24,268,277pKb, 208 Polyquaternium-27,265Placebo control, 362 Polyquaternium-28,261,262Plaque formation, 245 Polysaccharides, 16,241,258Plasmine, 161 Polysiloxane, 202, 203,275 {see alsoPolarized light photography, 338,344, Dimethicone, Silicone) 345 Polytrimonium gelatin, 160Polyacrylic acid, 158 Polyunsaturated fatty acids, 44,118Polyamine derivatives, 257,276 Polyvinyl chloride, 133Polycarbonate, 320,321 Poly-N-vinyl-2-pyrrolidone, 258-262,Polycationic resins, 241Polydimethylsiloxane, 167,168,171, 269 Pomade, 59,82,157 175-184,188,192,193,242,273, Pomades, 58,82, 83,157,302,312 274,2Wl{see also Dimethicone, Pore size/sebum excretion studies, Silicone)Polyethylene glycol, 100,220,241 362Polyethylene terephthallate, 133 Potassium cocoyl hydrolyzed collagen,Polymer, 10,28,58,95,108,133,136, 139,161,167,168,169,176,181, 157 203,251 Preservatives, 70, 80,95,99,105,183,Polymethyacrylamideopropyl tri- monium chloride, 258,264 184,194Poly(methacrylamidopropyltrimethyl Preshave products, 258 ammonium chloride), 322 Proctor and Gamble, 282,283Polymethylacrylaminopropyl tri- Product development, 29,225,281, monium chloride, 258Polyol, 99,154,162,183-185,190, 285,297,300,327,332 194 Product profile, 9,285-287,296Polyoxyalkylene glycol, 209 Propylene oxide, 129,178,232Polyoxyethylene, 178,193,206,218, Propyltrimonium hydrolyzed collagen, 231Polypeptides, 16,29,139,141,145, 157,160 155,156,160,162,164,234,254, Prostaglandins, 118 270,304, 333 Protease, 158,162Polyquaternary species, 240 ProteinPolyquaternium-4,268,277Polyquaternium-5,264 amino acid distribution of, 146Polyquaternium-6,262,263 containing sulfhydryl groups, 145Polyquaternium-7,227,255,263 degradation of, 29, 301Polyquaternium-10,227,255,258, effect on skin, 143 266-270, 277, 320 effect on hair, 143 formulation stability, 145-147 in hair structure, 21-22 hydrolyzates, 141-143,147,155-160, 162,164, 276 net charge, 147 in skin structure, 3,15-17,35,39

380 Index[Protein] Quaternized collagen hydrolysates, use in hair conditioners, 28,143,147, 234,271 243,275 use in skin conditioners, 105,141, Quaternized coUagens, 271 143,158 Quaternized ionenes, 265 Quatemized polyvinyl octadecyl ether,Prototype, 295,313,325,327,331Pruritis, 6 (see also Itching sensation) 264PUFAs (see Polyunsaturated fatty ac- Quaternized protein hydrolyzates, ids) 156Pump sprays, 241 Quaternized wheat protein, 272 Questionnaires, 326,341,342PVP (see Poly-N-vinyl-2-pyrrolidone)PVP-alpha-olefin copolymer, 259 Radial compressibility method, 309PVP/dimethylaminoethyl methacry- Radiotracer studies, 37,304 Rancidity, 115,242 late copolymers, 260,261 Rating system, 327PVP/Eicosene, 260 Reflected UV light photography, 344,PVP/ethyl methacrylate/methacrylic 345 acid, 262 Refractive index, 179PVP/ethyl methacrylate/methacrylic Relaxer, 82, 83,271 Removability of conditioner, 316 acid, 262 Retin A, 282PVP/hexadecene, 260 Retinoids, 43,340,362PVP/methylvinylimidazoline, 262 Rheology, 180,267,326PVP/VA, 259,269 Ring compressibility method, 309PVP/VA copolymer, 259,269 Rinse-out conditioner, 190Pyrrolidone carboxylic acid, 26,100, Robbins, Clarence, 2,11,199,235, 104,270 238,303, 333 Rubine dye, 303,324Quality control panel, 327Quartz, 167 Salon testing, 296,325-327Quaternary alkyl salts, 322 (see also Salts, 58,100,104,141,143,144,147, Quaternary ammonium com- 154,158,193,194,211,217,238, pounds) 245Quaternary ammonium compounds, antiperspirant, 173,185 28,227,251,254-256,325,333 Saponification, 40 definition, 223-234 Saponin esters, 241 and fatty acids, 157,208,213,215 Scalp formulation considerations, 238-244 condition of, 9,17,19,20,23,80-82, function of, 236-238,257 302,344 and proteins, 156,157 hair, 21,27,28 and silicone compounds, 209-211 Scanning electron microscopy, 261, types of, 258,283,295,308,323-325 325,352,362 use in hair care, 223 Screening panel, 327Quaternary germicides, 227 Sebaceous follicles, 362Quaternium-76 hydrolyzed collagen, Sebaceous gland, 17,19,20,363 144,157 Seborrhea, 363Quaternium 80,243,274Quaternized chitosan, 270

Index 381Sebum [Silicones] composition of, 20 derivatives of, 203-220,242-245,273, functions of, 6,17-18,23,27,362- 275,282 364 description of, 167 measurement of, 352 formulation examples of, 182-186, production of, 17 192 history of, 168-169,201-202,234Sebutape patches, 352,363 as occlusives, 26SEM (see Scanning Electron Micro- replicas for skin testing, 338,353,361 and static charge, 323 scope) trends in hair care using, 195-196Semipermanent dyes, 318 trends in skin care using, 186-187Sensitive skin, 341,361 volatile, 5Sensorial esthetics, 173Sensory perception, 178,333 Silicone surfactant, 204,206,211-213,Serine, 45,140,141,149,151,152, 220 162 Siloxane fluid, 168Serine protease, 162 Siloxane polymers, 10,167-200Setting lotions, 186,253,272,276Shadow silhouette hair tress method, history of, 167,168 manufacture of, 168 238 properties of, 170,171,187,189Shellac fixatives, 254 Siloxanes, 10,167-173,175,177-181,Shine 183-196,198,199,242,243,273 definition of, 4,23,27,28 Skicon skin surface hydrometer, 345, increasing amount of, 28,58,82,153, 362 161,189,265,286,310-313 Skin measurement of, 303,310Side effects, 43,241 appearance of, 4Silanes, 167,169 (see also Silicones, Di- color of, 4,160,338,352 damage, 3,24,25,72,81,337 methicone, Polydimethylsilox- disease, 24, dryness, 72,73,338,359,361 ane) elasticity, 5,7,160-162,350,352Silanic hydrogen, 205,207 evaluations, 338-364Silanol, 204,208,209,213 frictional properties of, 7Silica, 167,168 growth, 16Silicon dioxide, 167 innovations in the care of, 282Silicone alkyl quaternaries, 242 irritation, 86,105,144,160,180,181,Silicone betaines, 242Silicone carboxy quaternaries, 242 217,286,295,337Silicone complexes, 213,215 lubricants, 81,283 (see also Emollient)Silicone esters, 218 luminosity, 352Silicone fluids, 202-204 penetration (see Penetration of ingre-Sihcone phosphate esters, 216-218Silicone phosphobetaines, 242 dients into skin)Silicone-protein copolymers, 273,275 protectant monograph, 175Sihcone quaternium, 209-211 protectants, 80,81,87,175,197Silicone replicas, 338,353,361 sensitivity, 340,341Silicones (see also Dimethicone, structural components, 3,4,14-19, Siloxanes) 40-46,79

382 Index[Skin] Static electricity {see Static charge) surface, 6,11,16,27,29,57,72, Stearalkonium chloride, 144,157,214, 337-339, 345,359,362,363 tautness, 159 215,227 texture, 162 Stearic acid, 26,106,107,113,114,Sodium hyaluronate {see Hyaluronic 128,131,134 acid) Stearyl octyl dimonium chloride, 241 Step-growth polymerization, 252Sodium hydroxide, 102,121,155 Sterol, 18,116Sodium lauroamphoacetate, 231 Stick products, 178,219Sodium lauryl sulfate, 81,107,157, Straightening hair, 82 Stratum corneum 160,189,211,214Sodium polystyrene sulfonate, 276 description of, 15-18Sodium stearate, 99,220 lipid profile, 18,42Solubility role in perception of skin condition, of humectants, 99,104 25,26 ofIipids,57,121,129 structure of, 35-42,162,338,350 of polymers, 256,262,270,277 surface damage, 1,301 of proteins, 140,141,146,154, two compartment model of, 35 water content, 25,69, 70, 111, 345 157-159 Stratum germinativum, 15 ofquats,228,231,238 Stratum granulosum, 15,17,36,38 of silicones, 176,178,193,202,203, Stratum spinosum, 17 Stress, 99,155,187,237,309 209,216, 217 Structural proteins, 39,140,146 {seeSoluble collagen, 146,158Solvent extraction, 18,40,238 also Proteins)Sorbitol, 26,96-98,100,102-104,107, Styling, 5,24,28,58,82,157,180,188, 157 189, 255,259, 269, 272,277, 285,Soy protein, 272 286,301,312, 332Spectroscopy, 81,268,304,333,364 Styling gel, 272,312Spectroscopy techniques, 364 Subjective shine evaluation, 312SPF (see Sun Protection Factor) Sulfliydryl group, 144-146Sphingolipid, 18,45 Sulfur, 21,29,67Sphingomyelin, 40,41 Sunless tanning, 243Split ends, 9,153,253,257,266,267, Sun Protection Factor, 185,198,218, 221 302,303, 325 Sunscreen lotion, 185Stability Superoxide dismutase, 158 Surfactant penetration, 325 of emulsions, 147,178,193, 208,234 improving, 158 Tagami's sorption-desorption tech- oxidative, 115-117,127,128,131, nique, 145 132,144-146,158,175,243 Tape stripping of skin, 17,44 testing, 283,295,297,300 Taurine as a protein magnet, 156 thermal, 179 Technical innovations, 228,281,282Static charge, 24,28,235,237, 254, Teflon, 320,321 Telogen phase of hair growth, 20 270,277,320,327 {see also Combing properties)Static control, 157,234,240,241Static detector probe, 320,323,324

Index 383Tensile strength, 6,18,35,153,238, Two-in-one shampoo, 181,202 304,308,309 Tyrosine, 29,149,151,152,160Test panel, 361 Ultracentrifugation, 141TEWL (see Transepidermal water loss) Ultraviolet radiation, 18,28-29,Thermal treatments, 277Thickening agent, 159 81,158,243,285,344,345Three-dimensional HLB, 220 United States Pharmacopeia, 66,68,Three-dimensional structure, 134,139Three-in-one shampoo, 255 104Tin salts, 245 Unna, P. C, 14Tocopheryl acetate, 162 Urea, 26,72,73,78,107,145,158,265Toners, 8,159,258,363 Urokinase, 161Topical irritants, 209 U.S.P. (see United States Pharma-Toxicological test, 295Tracer dye, 238 copeia)Transepidermal water loss, 6,25,26, van der Waals forces, 170,235,257 46,57,69,72,72,73,76,80, 111, Vapor pressure, 176 159,160,350,359 Vaseline, 59 Vegetable proteins, 155,251 measuring, 350,359 Vinyl acetate/crotonic acid copolymer, modification of, 57,69, 73,76, 111, 276 159,160,161 Vinyl alcohol hydroxypropyl amine,Treatment sites, 358,359Triboelectric charging, 237,320-322, 264 Viscosity 324Triboelectric series, 236,237,303, of humectants, 98,103,104 impact of ingredients, 100,102,105, 320-324Tricetylmonium chloride, 228,238 124,129,131,134,135,159,193,Trichloromethyl silane, 168 211,225,229Trichoptilosis, 28 ofoils,68,86,131,134,136Tricotanyl PVP, 260 of polymers, 259,268Triethanolamine, 182 ofproducts, 99,147,326Triglyerides of silicones, 171,173,175,176,178, 194-196,202,204, 274 animal sources of, 117 Visible light photography, 344,345 as emollients, 112,122,123 Vitamin C, 161,162 marine sources of, 118 Vitamins, 26,97,161,162,287 melting points of, 114 VOC (see Volatile organic compounds) role in skin structure, 41 Volar forearm, 358,362 synthetic sources of, 135,219 Volatile organic compounds, 161,176 vegetable sources of, 114 Volatile siloxanes, 5,171,173,176,181Trimethylsilylamodimethicone, 192, Water 207, 208,273,274 in hair, 3,24,28,108Tristearin, 113,114 holding capacity of skin, 38,44,153,Tryptophan, 29,140,149,151,152, 339,350 and humectants, 95,99 301TSA {see Trimethylsilylamodimethi- cone)

384 Index[Water] Wool, 29,80,119,143,148,149,271,320 in products, 99 Work of adhesion, 319 repellency, 170 World Wide Web, 293 in skin, 3,15,15,24-26,36,57,59,77, Wrinkles, 7,153,154,164,283,337, 339, 345 343,344,353,361Wax, 18,26,61,63,66-69,73, 80,119, Wuhelmi balance method, 319 120,124,130,185,207,219,220 X-ray photoelectron spectroscopy,Weathering, 27,301,319 268,304Wet combing X-ray, 21,36,40,268,302,304,333 effect of ingredients, 158,188,191, Xerosis, 18,24,25,71 241,255,264,266,267,269,271, 273,274,276 Young-Dupre equation, 319 Young's modulus, 309 testing, 211,305,306Wettability measurements, 319 Zeiss dermavision system, 352Wetting force measurements, 319 Zeta potentials, 313,314,316,318Wheat protein, 105,149,155,156,159, Zinc pyrithione, 263 Zwitterionic surfactant, 245 161,272, 275Whey protein, 162Woodruff, J., 125,198