MCGH053-C70_[18-29].qxd 09/09/2008 05:05 AM Page 18 Aptara (PPG-Quark) CHAPTER 70 includes the impact of cosmeceuticals, VERTICAL STRUCTURE The cosmetics Cosmetic Products significant changes in the marketing of industry is composed of large conglom- cosmetics, historical milestones in the erates that use forward vertical integration Cheryl M. Burgess development and use of cosmetics, the to manufacture and market products. development of federal regulations, the According to this structure, large compa- formation of trade associations, and the nies set up subsidiaries that distribute or chemical formulation of cosmetics. market cosmetics to a variety of markets. After discussing the industry, the chap- What appears to the consumer as a host Key Points ter reviews various cosmetics products of different product lines is, in reality, a and ingredients, including antioxidants, collection of products distributed from a • There has been over $1 billion in general growth factors, sunscreens, botanicals, single research and development source. business growth for ethnic hair care, and Cosmoleculars. Most cosmetics manufacturers do not beauty, and cosmetics. use the practice of outsourcing develop- • The term cosmeceuticals describes a Impact of Cosmeceuticals ment and production. In order to respond DERMATOLOGY FOR SKIN OF COLOR product category that is intermediate to quickly changing demands of con- between cosmetics and pharmaceuticals. Almost 30 years ago, Albert Kligman sumers, production facilities must contin- • The cosmeceutical market is driven by the introduced the term cosmeceuticals to ually adjust the production processes. antiaging market. Baby boomers comprise describe a burgeoning product category Outsourcing the production process the largest market share. that was intermediate between cosmetics would increase the time to bring a new • The cosmetic industry is governed by the and pharmaceuticals.2 Loosely defined, product to market.6 Food, Drug, and Cosmetic Act and volun- cosmeceuticals are any cosmetic, skin care, tary regulatory programs such as the hair care, body care, foot care, or other THE CONSUMER Marketing strategies are Cosmetic, Toiletry and Fragrance products that treat or prevent a medical also changing in response to changing Association (CTFA) and the Cosmetic condition even as they beautify.3 The mar- consumer demographics and consumer Ingredient Review (CIR). ket impact of cosmeceuticals is staggering: demands. America’s aging baby boomers, • The process of cosmeceutical product While the United States saw a 1% annual numbering 78 million, traditionally have develop involves formulation, vehicle, increase in the sales of skin care products driven the market for antiaging or active ingredient, and preservative consid- in 2003, sales of cosmeceutical brands had other cosmeceutical products. However, erations. an incredible 83% increase.4 According to today’s market is driven by a new seg- the Fredonia Group, cosmeceutical rev- ment of nontraditional consumers as enues in the United States are projected to well. For example, increased discre- top $5.1 billion by 2007.5 Today, hundreds tionary spending by growing middle- ABBREVIATIONS of products include vitamin supplements, class populations in Russia and Asia is AHA -hydroxy acid antioxidants, and growth factors. also driving sales. In addition, the chil- CoQ10 coenzyme Q10 dren of baby boomers, generations X, Y, CIR Cosmetic Ingredient Review Marketing of Cosmetics Z, etc., are also fueling the sale of cos- CTFA Cosmetic, Toiletry, and Fra- meceuticals, and males 18–30 years of grance Association The marketing of today’s cosmetics is no age are now targeted as another key FDA Food and Drug Administration longer restricted to the pharmacy and growth segment.5 FDCA 1938 Food, Drug, and Cosmetic department store. In fact, sales in the tradi- As today’s consumers grow more Act tional big retailers have been in a decline. knowledgeable about the physiology of OPC oligomeric proanthocyanidins In contrast, cosmeceutical products are their own skin, these consumers seek OTC over the counter now widely available from diverse mar- more science in personal care products SC stratum corneum keters, including mass, prestige, and alter- and demand scientific data to back up TEWL transepidermal water loss native distribution channels5 (Table 70-1). marketing claims. As a result, clinical studies are often cited, regardless of the quality of scientific data, and doctors are OVERVIEW TABLE 70-1 increasingly becoming the spokesper- For the past 50 years, the cosmetics Places to Purchase Cosmetics5 sons for skin care brands, adding to the industry has surpassed revenue expecta- Mass-market retailers credibility of these brands in the mar- tions as one of the fastest-growing and Direct-market retailers ketplace. Mass marketers are not only most profitable market sectors in the Prestige retailers aligning with physicians to compete United States. By all accounts, it appears Specialty stores with doctor-owned brands, but the that the new millennium will continue Health spas industry is also experiencing buyouts of this record-breaking trend, and today, the Beauty salons smaller, doctor-driven brands by the growth continues as many companies Health clubs and gyms larger companies. In addition to wanting expand into overseas markets and capi- Physician’s ofﬁces (including plastic sophisticated products with stable, effi- talize on new market segments, such as surgeons, dermatologists, ophthalmologists, cacious active ingredients, consumers the fast-growing cosmeceuticals market.1 internists, dentists) are asking for nonsurgical, noninvasive This chapter discusses several aspects Internet boutiques treatments that can be accomplished of cosmetics use, beginning with an Infomercials without visiting a clinic. To this end, 18 overview of the industry. The discussion several products have been positioned MCGH053-C70_[18-29].qxd 09/09/2008 05:05 AM Page 19 Aptara (PPG-Quark) as a less drastic approach and an alterna- ical perfection. Richard Fried writes, and product stability. Today, many com- tive to the dermatologist’s office.5 “Healthy cosmesis lies midway between panies conduct cosmetics research with total self-neglect and extreme the same safety and testing methods ETHNIC MARKETS Another growth area makeover.”8 He notes that the dermatolo- used by pharmaceutical research and in cosmetics is specialized ethnic popula- gist can play an integral role in the development.5 tions, evidenced by the large success of patient’s decision-making process, pro- products targeting the African-American, viding clarity in a market that is perme- Development of Cleansers and Hispanic, and Asian-American markets. ated with unsubstantiated claims.8 According to market predictions, general Marketing claims tout the miracle- Moisturizers business growth for the ethnic hair care, like effects of cleansers, moisturizers, Some of the earliest cosmetic therapies beauty, and cosmetics market will reach skin supplements, and antiaging prod- were introduced by Galen, a Roman $40 billion by 2011. Products expected to ucts. However, clinical studies that sup- physician/cosmetician who invented grow in the ethnic markets include fade port these claims of miracle-like efficacy cold cream, an emulsion of olive oil and creams and gels, cleansers, toners, astrin- are often absent, flawed, or based on beeswax. Much later, in the early 1900s, gents, soaps, emollients, moisturizers, very small study populations, and many Paul Gersen Unna introduced Unna’s and antiwrinkle products. In the ethnic times the only clinical data are available boot, essentially a zinc oxide paste that market, products that target skin discol- from the product’s manufacturer.4 is still the therapy of choice for stasis CHAPTER 70 ■ COSMETIC PRODUCTS oration are experiencing the best con- ulcers. Petrolatum was introduced in sumer response.7 1872 and has been hailed as the moistur- For African-American consumers, HISTORY OF SKIN CARE izer par excellence without a serious rival uneven skin tone, sensitive skin, and in more than 100 years.2 acne-prone skin are the most problem- PRODUCTS atic areas. Products targeting the Development of the Cosmetics African-American market have been REGULATORY AGENCIES most successful when sold at the mass- Industry market and drugstore levels, as demon- Cosmetics were used for religious, med- History of Regulation strated by the success of certain ethnic ical, and personal care purposes by Unlike the long history behind the devel- products sold in Walgreen’s and Wal- ancient societies that included the opment of the cosmetics industry, the Mart stores. Ethnic skin care lines are Egyptians, Chinese, and Indians. Based passage of government regulations to handled more often through distributors in part on ancient Egyptian pharma- establish the safety of cosmetics is a fairly compared with general-market prod- copeia, the growth of cosmetics contin- recent historical development. The pas- ucts. This is so because successful mar- ued to develop in Rome and Greece. For sage of the Food, Drug, and Cosmetic Act keting of ethnic products requires care- several centuries, Rome remained a cen- (FDCA) in 1938 marked the beginning of ful use of finely tuned distribution ter of important cosmetic development, legislation to protect the consumer from channels. Cofounder Dr. Cheryl Burgess evidenced by the formulation of the first unsafe cosmetic formulations.1 and representatives of U.S. Black Opal cold cream by Galen (AD 130–200). The Beginning in the 1800s, a growing note the success of distributors with Islamic culture encouraged the develop- problem with tainted medications and operations in the United Kingdom, ment of the beauty culture and con- food preservatives led to grass roots including destinations in the Caribbean, tributed great advances in the use of groups such as the Pure Food Movement, Botswana, Brazil, and Zaire.7 botanical treatments for cosmetology. which helped to generate support for Certain ingredients are extremely The thirteenth century marked the regulatory reforms that were made law popular among African Americans, includ- beginning of a divergence between for- by the Pure Food and Drug Act of 1906 ing -hydroxy acid (AHA) and cocoa malized medicine and the science of (PFDA). However, the far-reaching legis- butter—AHA reduces the ashy appear- cosmetology.9 Moving forward, the cos- lation was stripped of its main powers of ance of skin in some African Americans metics industry increasingly focused on enforcement prior to becoming law.9 by speeding up the natural process of the science of beauty, leaving behind Concerns for consumer protection sloughing off dead skin cells, and cocoa medicine. Cosmetic products would not continued to fulminate in the 1900s, butter has helpful emollient properties.7 share medical status again until the mainly at the state level. Politicians, rec- Another indicator of the success of flourishing of cosmeceuticals in the ognizing a populist cause, exploited the products targeting ethnic populations 1980s. Indeed, the debut in 1983 of horror stories (partly true, partly tall tale) is the acquisition of cosmetics compa- these hybrid products—merging the illustrating the terrible harms caused by nies in non-Western countries, for research interests of science, medicine, unregulated medications and cosmetics. example, L’Oreal’s purchase of Yue Sai and beauty—marked the birth of the The reform movement also was aided Kan Cosmetics and Carson, Inc.7 modern cosmeceuticals industry.10 by a series of highly publicized books By the eighteenth century, most cos- that demonized the practices of the PERVASIVE MARKETING VERSUS HEALTHY metics were formulated in private food, drug, and cosmetics industry. COSMESIS The continued growth of the homes from ingredients purchased at These events eventually culminated in cosmetics industry is not terribly difficult pharmacies. By the nineteenth and formulation of the 1938 Food, Drug, and to understand given America’s obsession twentieth centuries, several important Cosmetic Act.1 with perfect physicality and perfect developments in the formal regulation Provisions of the act addressed both beauty. Whether from Hollywood, the of the industry helped to shape the adulteration and misbranding controver- cosmetics industry, or even the medical modern-day cosmetics industry.5 With sies. For example, the act states that a health profession, Americans receive a the advent of formal regulation, the cosmetic is considered adulterated if it steady dose of media images and mes- industry began gaining consumer confi- “contains any poisonous or deleterious sages instructing consumers to obtain phys- dence through improved safety, efficacy, substance that may render it injurious to 19 MCGH053-C70_[18-29].qxd 09/09/2008 05:05 AM Page 20 Aptara (PPG-Quark) users under customary conditions of place of the more reserved Victorian ernment officials, medical professionals, use.” In addition, the misbranding provi- style, experienced an explosion of and consumers to provide timely alerts sions prohibit labeling that is “false or growth. In 1937, the organization— regarding important ingredient safety misleading in any particular way.”11 renamed the American Manufacturers information.1 Labeling provisions required by the FDA of Toilet Articles—gave support to the Throughout the last quarter-century, for the cosmetics industry include (1) basic tenets of the legislation that would the CTFA has helped industry, govern- proper cosmetic labeling, (2) declaration lead to the 1938 Food, Drug, and ment, and consumers steer through of ingredients, (3) label warnings, (4) Cosmetic Act and lobbied for federally many difficult social and legal challenges tamper-resistant packaging, (5) contents standardized regulations in place of a in cosmetics; for example, efforts to quantity, and (5) the name and address patchwork of state laws.1 work with animal rights groups, safety of the manufacturer, packer, and distrib- In the 1970s, the CTFA worked testing of color additives, and regulation utor. The FDA defines cosmetics as arti- closely with the FDA to establish a sys- of volatile organic compounds, to name cles “intended to be rubbed, poured, tem of voluntary regulation, in which a few.1 sprinkled, or sprayed on, introduced the industry provided regular registra- The CTFA founded Look Good Feel into, or otherwise applied to the human tion of manufacturing establishments, Better—an initiative to advance the body or any part thereof for cleansing, submission of data on finished products, awareness and special use of cosmetics beautifying, promoting attractiveness, and reporting of consumer complaints. by cancer patients—and launched sev- DERMATOLOGY FOR SKIN OF COLOR or altering the appearance” while main- In the 1970s era of consumer and envi- eral initiatives to create funding for the taining the structure and function.11 ronmental concerns, the CTFA’s pro- program. Look Good Feel Better is Throughout the 1900s, regulation of gram of voluntary regulation demon- funded by the cosmetics industry cosmetics was further defined, amid a strated the industry’s willingness to through the CTFA foundation to help continuing battle between consumers, supply information to the FDA while female cancer patients overcome the manufactures, trade organizations, politi- discouraging congressional legislation at appearance-related side effects and help cians, and the government—culminating the same time.1 Today, about 40% of to improve patients’ self-esteem. in establishment of a voluntary regula- manufacturers voluntarily register their tory program (discussed below). products with the FDA.13 INTERNATIONAL COSMETIC INGREDIENT In 1973, the first edition of the DICTIONARY The desire to normalize the COSMECEUTICALS: REGULATORY DILEMMA Cosmetic Ingredient Dictionary was pub- process of describing botanical ingredi- The dual nature of cosmeceuticals pre- lished. The publication eventually ents began in the United States. In the sents new challenges to lawmakers for gained international acceptance and 1990s, an explosion of interest in classifying and regulating these prod- would later provide an instrument for botanicals drove the earliest rules for ucts. The challenges range from funda- proper cosmetic ingredients labeling.1 identifying and labeling botanical mental questions to practical concerns. The 1970s saw continued pushes for ingredients. At first, ingredients were For example, should regulators reclassify increased regulation of cosmetic ingredi- labeled intuitively, for example, from a drugs as cosmetics when manufacturers ents labeling. Although the CTFA common name, such as apple or orange. remarket products—not for their origi- opposed the attempts to remove the vol- However, as ingredients became increas- nal therapeutic effect—but for newly untary regulation program, the CTFA ingly more specialized, it became appar- discovered cosmetic side effects? Could eventually found itself working with the ent that new rules for assigning names drug vehicles themselves—absent any FDA to establish legislation, and in 1976, would be required. In addition, the intu- active ingredients—be given drug status it supported further regulations on itive terms developed in the United based on their therapeutic effects as ingredient labeling. Manufacturers were States were of little use internationally. occlusive agents? In some cases, regula- required to substantiate the safety of With the help of the CTFA International tors have attempted to distinguish drugs their products or include a warning Nomenclature Committee, several meet- from cosmetics based on the concentra- statement that the safety of the product ings were held in the United States and tion of an active ingredient. However, had not been determined.1 internationally. As a result of the meet- no scheme is without drawbacks. Also evolving in the 1970s was the ings, the CTFA recommended that new Consider that the efficacy of AHA is creation of another landmark volunteer rules recognize scientific terminology, more dependent on the design of the regulatory program, the Cosmetic using Latin genus and species names, as vehicle than on the concentration of Ingredient Review (CIR). The CIR was the basis for botanical-derived ingredi- AHA. As the cosmeceutical market established as a voluntary program to ents in nomenclature. In 1995, the sixth grows, the regulatory difficulties are cer- evaluate published and unpublished edition of CTFA’s International Cosmetic tain to be compounded.12 data on cosmetic ingredient safety. Ingredient Dictionary introduced the label- Today, the Expert Panel of the CIR is ing of botanical ingredients, showing Cosmetic, Toiletry, and Fragrance composed of scientists from the disci- both Latin and common botanical plines of dermatology, pharmacology, names.1 Association (CTFA) chemistry, and toxicology who have The CTFA was founded in 1894 as the been publicly nominated by consumer, Manufacturing Perfumes Association. scientific, industry, and government GENERAL BACKGROUND The first decade of the association’s agencies. The CIR program provides an existence was devoted primarily to fur- open forum to present safety informa- Product Development thering the industry’s interests by help- tion and encourages congressional and FORMULATIONS The formulation of a ing to repeal several major tariffs and public discourse.1 dermatologic product must satisfy cer- taxes. The association was very active in The CTFA is also responsible for tain requirements that include bioavail- the 1920s as the cosmetics industry, Cosmetic Industry ON CALL, a publica- ability of an agent, chemical and physical 20 boosted by the emerging flapper look in tion created for industry members, gov- stability, freedom from contamination, MCGH053-C70_[18-29].qxd 09/09/2008 05:05 AM Page 21 Aptara (PPG-Quark) and patient acceptability. Satisfaction of three measures: (1) pharmaceutical or lenged, with regard to actual ingredients these requirements becomes a complex chemical equivalence, (2) bioequiva- or scientific basis. A few of these terms challenge when designing a delivery lence of the active ingredient, and (3) are presented below. vehicle in conjunction with a specific therapeutic equivalence. For topical for- target site for products applied to the mulations, measuring bioavailability is Alcohol-Free Cosmetics that are labeled skin. Cosmetic products may target the more involved because active ingredi- “alcohol-free” are sometimes chosen by skin surface, the horny layer, sweat ents are present in very low concentra- consumers because they believe that ducts, or living skin cells. To reach one tions in these formulations. The low alcohol will dry out their skin or hair. of these targets, a vehicle must be indi- concentrations are problematic because However, alcohol-free only pertains to vidually designed to accommodate the they lead to difficulties in accurately the absence of ethyl alcohol. Cosmetic specific needs of a therapeutic agent and measuring the concentration of active products, including those labeled “alco- a specific therapeutic target. Therefore, ingredient in blood, and blood levels are hol-free,” still contain other alcohols, product formulation and vehicle design often not representative of the concen- such as cetyl, stearyl, or lanolin alcohol. are almost synonymous.14 tration at the target site—the skin. As These alcohols, known as fatty alcohols, shown in Table 70-2, generics are have a variety of effects quite different DERMATOLOGIC VEHICLE Dermatologic allowed significant variation from from those of ethyl alcohol.16 vehicles include topical liquids (lotions or brand-name drugs. Even small modifi- CHAPTER 70 ■ COSMETIC PRODUCTS liquid emulsions), anhydrous and hydrous cations to a product vehicle cause sig- Hypoallergenic When cosmetics are semisolids, patches and tapes, liposomes, nificant changes in therapeutic efficacy. labeled “hypoallergenic” or “allergy and microparticles. Some basic questions This may call into question any assump- tested,” many consumers assume that in the development of a delivery system tions of true equivalence.15 ingredients contained in the product are may be answered early on. For example, gentler to the skin or safer than nonhy- what degree of occlusion will be needed, LABEL TERMS THAT MISLEAD The market- poallergenic cosmetics. However, both or will a penetration enhancer be ing of cosmetics often relies on the use of dermatologists and the FDA say the term required? Occlusion affects the percuta- promotional terms such as fragrance-free has very little meaning. Indeed, the FDA neous absorption of a product by chang- and hypoallergenic to suggest that a prod- states that “almost all cosmetics can ing the hydration of the SC and raising uct has special characteristics. These cause allergic reactions in certain individ- skin temperature. Penetration enhancers product claims often cause consumers to uals.”17 The FDA provides no federal change the normal resistance of the SC.14 form grand assumptions about product standards or definitions to govern the ingredients. Unfortunately, these promo- use of the term, and manufacturers of PRESERVATIVES Cosmetics can suffer tional terms have very imprecise mean- cosmetics labeled “hypoallergenic” are degradation through oxidation and ings and may mislead consumers about not required to substantiate their claims. hydrolysis. Microbial growth can produce the actual qualities and ingredients of a Not surprisingly, the FDA found that a enzymes that cause degradation of active cosmetic. In many cases, consumers majority of cosmetics labeled “hypoaller- ingredients and change pH. Preservatives simply jump to conclusions, such as the genic” contained the same ingredients as are generally required for any topical assumption that “natural” products are nonhypoallergenic cosmetics.17 product containing water. Preservatives superior. In other cases, federal stan- prevent or limit fungal and bacterial dards or definitions are entirely absent, Natural or All Natural Many consumers growth and contamination—after the leaving claims about ingredients unchal- also believe that “natural” or “all natural” product is manufactured, during storage, and in the hands of the consumer.14 Au1] Vitamin E (tocopherol) and EDTA are TABLE 70-2 common preservatives in cosmetics.1 Terminology of Generic Drug Evaluation15 ACTIVE INGREDIENTS The use of generic TERM COMMENT drugs has helped the health care and Therapeutic equivalence A comparison of the therapeutic efﬁcacy and toxicity proﬁle of health insurance systems to extend ther- two different drugs given by the same dosage regimen to apies to many patients who, without patients being treated. generic pricing, would not be able to sus- Bioavailability The rate at and the extent to which an active ingredient is tain prescription drug costs. However, absorbed from the site of administration and reaches the these benefits are not afforded without a systemic circulation. tradeoff. In several cases, the inter- Bioequivalence A comparison of the relative bioavailability of two different drug changeability of products leads to ther- products in the same test population. apy failure. This can be the result of (1) Pharmaceutical equivalence Constant Variable failure of a vehicle to deliver enough Active ingredient Inert ingredients (binders, active ingredient or (2) patient noncom- Strength ﬁllers, excipients) pliance that results when inert ingredi- Route of administration Color ents in the vehicle cause adverse effects. Dosage form (tablet vs Flavor Most disturbing is the misinterpretation capsule) Shape by a clinician that an active ingredient Scoring has failed when the culprit actually may Conﬁguration be the generic’s vehicle.15 Packaging Shelf life Generic Evaluation The interchangeabil- Manufacturing process ity of two formulations is evaluated by 21 MCGH053-C70_[18-29].qxd 09/09/2008 05:05 AM Page 22 Aptara (PPG-Quark) ingredients are better for the skin. cancer caused significant ramifications in guish between unwanted dirt and However, the FDA warns that the implied the preservative industry and led some important intercellular lipids. Certain superiority of natural ingredients is based manufacturers to seek preservative-free lipids in the SC contribute to the water- neither in fact nor in scientific legitimacy. systems to control microbial growth and holding function of the SC.23–25 The Moreover, there is no official government prevent product deterioration. However, water content in the SC is largely respon- definition for natural or all natural.18 “All industry efforts have not yielded a satis- sible for the flexibility and amount of natural” products contain plant-derived factory solution that is readily adaptable shedding in this layer. The uptake of substances that are conducive to micro- to current manufacturing requirements.21 water and water-holding capacity, in bial growth, causing them to have an In Japan, a different approach has turn, depends primarily on the quantity unusually short shelf life. Consumers and been taken by the Fancl Corp. In 1999, of natural moisturizing factor (NMF)— manufacturers should carefully consider Fancl built a $45 million manufacturing the water-soluble hydroscopic and sur- the risk of contamination in products that facility to execute the company’s 25- face-active materials present in the contain nontraditional preservatives or no year-long preservative-free philosophy. SC.26,27 When soap disrupts the NMF, it preservatives at all.13 The new facility adopted a novel manu- reduces the skin’s capacity to retain facturing process that eliminated the water, and transepidermal water loss Fragrance-Free and Unscented Cosmetics need for adding preservatives to cosmet- (TEWL) leads to dry skin. labeled “fragrance free” or “unscented” ics. Much of this is accomplished Soap causes the pH of skin to change DERMATOLOGY FOR SKIN OF COLOR suggest that a product contains no fra- through automated processes that take and strips away valuable humectant grance or that no fragrance has been place in bacteria-free environments. The agents, resulting in irritant contact der- added. However, fragrance-free prod- company uses clean rooms, air filtration, matitis.28 An alternative to soap is syn- ucts may contain fragrance ingredients and vigilant quality control to keep dets (synthetic detergents). Although in small quantities to mask offensive products from becoming contaminated syndets remove less unwanted dirt, syn- odors caused by various ingredients, for with bacteria. Many of the processes dets spare more intercellular lipids, and example, the fatty odor of soap. Most meet medical and pharmaceutical man- the pH remains adjusted.28 The use of manufacturers list these small quantities ufacturing standards.22 syndets leaves the skin more capable of of fragrance among their ingredients, retaining moisture and thus avoids dry- even though the FDA requires no such ing the skin out. labeling.19 COSMETIC PRODUCTS It is important to avoid certain addi- tives in cleansers, especially if there is a Cleansers Preservative-Free Consumers also believe history of sensitive skin. Examples a product is superior, natural, or less Cleansers generally fall into two cate- include detergents such as sodium lauryl harmful to skin if labeled “preservative gories: soap and synthetic detergents. sulfate, parabens, and fragrances.28 free.” However, most cosmetic prepara- Soap, the most common known cleanser, Table 70-3 lists several types of cleansers tions require preservation to prevent damages skin because it fails to distin- and their main attributes. spoilage owing to microbial action or to retard oxidative deterioration, particu- larly that of fats and oils. Many of the components of cosmetics can serve as TABLE 70-3 substrates for microbes, and contamina- Cleansers28 tion of a cosmetic, usually from airborne bacteria or fungi, can cause partial or TYPE OF CLEANSER FORMULATION COMMENTS total deterioration of the product.20 Soap Composed of anionic surfactants There are no regulations requiring cos- Drying and irritating to skin metic manufactures to indicate the shelf Raises pH of skin (neutral to alkaline) life on the labels of their products. Superfatted soap and beauty bars Composed of anionic surfactants However, voluntary shelf-life guidelines Drying and irritating to skin have been developed by the cosmetics Causes follicular plugging industry. For example, products used in Raises pH of skin (neutral to alkaline) the area of the eye have a shorter rec- Emollient may be added to reduced dryness ommended shelf life. Accordingly, Dermatologic bars/cakes Composed of amphoteric, anionic, and nonionic surfactants industry experts recommend replacing May raise pH of skin mascara 3 months after purchase.13 Emollient added to reduced dryness and irritation Some products labeled as “preserva- Cosmetic liquid cleansers Composed of amphoteric, anionic, and nonionic and tive free” actually may contain preserva- silicone surfactants tives. This is so because manufactures Can be mild and less irritating to skin can exploit loopholes in the regulations Generally have pH similar to skin to make preservative-free claims. Manu- Generally have emollients and humectants added factures can exclude preservatives from Antiseptic and antibacterial washes Composed of amphoteric, anionic, and nonionic surfactants the ingredients label if raw material used May raise pH of skin in the product was preserved unnecessar- Emollients added to reduced dryness and irritation ily or if a raw material is overpreserved Adjunct to acne treatment using any preservative, whether synthetic May help control bacteria, not believed to penetrate follicle or natural.21 Potentially less irritating and drying than topical In 2004, concerns about the possible bactericide. 22 connection between parabens and breast MCGH053-C70_[18-29].qxd 09/09/2008 05:05 AM Page 23 Aptara (PPG-Quark) gen, glycosphingolipids, glycosamino- TABLE 70-4 glycans, hyaluronic acid, lecithin, Moisturizer Ingredients28 phospholipids, polysaccharides, pro- TYPE OF INGREDIENT teins, pyrrolidonecarboxylate, sodium (FUNCTION) EXAMPLES SIDE EFFECTS AND PROBLEMS hyaluronate, sorbitol, sodium PCA, Occlusive agents sugars, and urea. Some of these may [Au2] (block water loss in Lanolin, mineral oil, Messy cause irritation (e.g., urea and lactic the stratum corneum) petrolatum Some can cause folliculitis acid)28 (see Table 70-4). May clog pores May cause contact dermatitis EMOLLIENTS Emollients provide a soft, (lanolin) smooth feeling that consumers desire. Can block hair follicles and cause The smooth feeling is actually achieved pustules (folliculitis) or boils by filling in spaces between skin flakes. Can aggravate acne or cause an Emollients are classified according to unsightly facial rash, perioral their composition. Hydrogel emollients dermatitis are either surface-active, providing a CHAPTER 70 ■ COSMETIC PRODUCTS Humectants (hydroscopic -Hydroxy acids, amino Some may cause irritation thin layer at the surface, or they are car- substances that attract acids, collagen, elastin, (urea, lactic acid) bomer gels, which penetrate deeper into moisture) glycerin, glycogen, the skin. Oil-in-water emollients come glycosphingolipids, in the form of lotions or creams. These glycosaminoglycans, emollients posses a hydrophilic external hyaluronic acid, lecithin, phase with superb absorption rates. phospholipids, Emollients can be incorporated easily polysaccharides, proteins, into products.28,30 On the other hand, pyrrolidone carboxylate water-in-oil emollients have a lipophilic (NaPCA), sodium external phase. Since these emollients hyaluronate, sorbitol, mainly include petrolatum and/or paraf- sugars, and urea fin oil, they are aesthetically less pleas- Emollients (smooth and Cholesterol, fatty acids, Not always effective ing and usually are used in more chronic soften skin by failing myristates, palmitates, May cause allergic reaction disease situations30 (see Table 70-4). the spaces between squalene, stearates, Examples of common emollients skin ﬂakes) and triglycerides found in moisturizers include choles- Anti-irritants (reduce Allantoin, bisabolol, Not always effective terol, fatty acids, myristates, palmitates, itching and irritation) glycyrrhetinic acid, May cause allergic reaction squalene, and triglycerides28 (see Table and vitamin C 70-4). The most effective moisturizers Antioxidants (may aid in Selenium, superoxide Not always effective are anhydrous lanolin and petrolatum, cell turnover and dismutase, vitamin May be irritating which have very little water and proba- healing and may A (retinyl palmitate bly act by retarding loss of water.29 reduce dehydration) and retinol), vitamin To replace diminished moisturizing C, ascorbyl palmitate and barrier properties in cases of deficit and magnesium sebum production, future moisturizers ascorbyl palmitate, will contain optimal molar ratio of skin -glucan, vitamin E surface lipids that mimic synthetic ( -tocopherol, tocotrienol), molecules, such as pseudoceramides. curcumin, coenzyme Other products under development Q10, and -lipoic acid include the acrylate polymer, a spheri- cal microparticle that absorbs and binds sebum.31 Moisturizers mineral oils. It is highly recommended Sun Protection to apply occlusive agents right after Moisturizers assist in skin repair by cre- Terrestrial sunlight consists of ultraviolet cleansing to trap the maximum quantity ating a suitable environment for healing. B radiation (UVB, 280–320 nm), UVA of water in the skin28 (see Table 70-4). Moisturizers accomplish this by reduc- radiation (320–400 nm), visible light ing the loss of water and creating a bar- HUMECTANTS Humectants can improve (400–800 nm), and infrared (IR) radia- rier on the skin. Moisturizer ingredients the overall hydration of the skin by tion (800 nm and above). To protect can be broken into three basic cate- attracting moisture. However, when human skin from free-radical genera- gories: (1) occlusive agents, (2) humec- using high levels of humectants, an tion, skin has a sophisticated antioxi- tants, and (3) emollients28 (Table 70-4). occlusive agent also should be used to dant system that includes superoxide help prevent water loss from surround- dismutase, glutathione reductase, and OCCLUSIVE AGENTS Occlusive agents are ing cells. Without an occlusive agent to glutathione peroxidase. However, UV defined by their ability to stop or retard trap moisture, the skin actually could dry light damages skin throughout life water loss. Petrolatum is the superior out even further.28,29 Examples of com- because the cutaneous antioxidant sys- choice of occlusive agents.29 Other mon humectants include AHAs, amino tem is less than 100% effective. In choices include lanolin, silicones, and acids, collagen, elastin, glycerin, glyco- addition, these cutaneous antioxidant 23 MCGH053-C70_[18-29].qxd 09/09/2008 05:05 AM Page 24 Aptara (PPG-Quark) out about 20%. Although mineral oil TABLE 70-5 does not resist any UV rays, it helps to FDA Sunscreen Final Monograph Ingredients33 protect skin by dissolving the sebum DRUG NAME CONCENTRATION % ABSORBANCE secreted from oil glands, thus assisting Aminobenzoic acid 15 UVB evaporation from the skin. Tea tree oil is Avobenzone 2–3 UVA a popular component of sunscreen for- Cinoxate 3 UVB mulations that relieves sunburn by Dioxybenzone II 3 UVB, UVA increasing blood flow in capillaries and Homosalate 15 UVB bringing nutrients to damaged skin.33 Menthyl anthranilate 5 UVA Evidence is growing that the addition Mexoryl 8 UVA of antioxidants to sunscreen formula- Octyl methoxycinnamate 7.5 UVB tions can protect human skin against Octisalate 5 UVB UVB, UVA, and IR irradiation. In a study Oxybenzone 5 UVB of 30 patients, Muizzuddin and col- Padimate O 8 UVB leagues32 demonstrated significant pro- Phenylbenzimidazole sulfonic acid 4 UVB tection from a cocktail of antioxidants. Sulisobenzone 10 UVB, UVA Results indicated protection from UVB, DERMATOLOGY FOR SKIN OF COLOR Titanium dioxide 2–25 Physical UVA, and IR irradiation. Trolamine salicylate 12 UVB Today, the addition of antioxidants is common among cosmeceuticals, espe- cially for the purpose of treating photo- damaged skin. However, the investiga- systems themselves experience continu- potential to degrade other sunscreen tions of antioxidant use for preventing ous damage from the sun, compromis- ingredients.33 damage are in the very early stages of ing their effectiveness.32 For many years, It is recommended that all skin types research and development.4 scientists have known that UVB causes and ethnic groups be advised and encour- Clothing should not be overlooked as sunburn and serves as a surrogate for aged to use daily sun protection. The level an integral part of sun protection. Wide- more serious skin disorders, including of protection from sunscreen is indicated brimmed hats should be worn, and cancer. However, scientists have come using the sun protection factor (SPF). clothes should be chosen carefully with to believe that UVA also may contribute Although consumers readily understand an appropriate fabric. Loosely woven to skin disorders, including photoaging the meaning of the number—the higher fabrics may still transmit UV, up to 30% and skin cancers.32 the number, the greater the protection— of UV with wet fabrics such as swim- Sunscreens traditionally have been studies show that people often mistake suits. In addition, a white T-shirt has an categorized as chemical absorbers, the higher SPF number as meaning that SPF of 5–9, and UV-protective fabrics physical blockers, or both. Chemical they can stay in the sun longer. Indeed, raise the SPF to 30.33 sunscreens generally have aromatic studies have shown that using higher compounds that absorb high-density SPF sunscreens has led to increased sun UV rays, causing excitation to a higher exposure by consumers. In addition to Antiaging Formulations: Overview energy state (Table 70-5). When the mol- consumers misusing the SPF information, Just as antiaging products overtook the ecules return to the ground state, the other problems exist. Consumers fail vitamin and supplements industry in the energy absorbed in the photochemical to correctly apply sunscreens—applying 1990s, antiaging products, referred to as process causes the emission of longer, too little, too infrequently—perhaps as a cosmeceuticals are flooding the cosmetics safer wavelength radiation. Physical result of labeling confusion. Descriptors marketplace. However, because the blockers are opaque compounds that such as “sun block,” “all-day protection,” therapies are not classified or marketed reflect the sun’s light. Recent research “broad spectrum,” “waterproof,” and as drugs, cosmeceuticals lack FDA over- indicates that the newer micronized “water resistant” are misleading, espe- sight, and many claims go unsubstanti- forms of physical blockers also may cially since all sunscreens allow some ated. Before recommending antiaging function in part by absorption.33 portion of damaging UV radiation to pen- therapies, dermatologists should seek etrate the skin.33 clinical data on the efficacy of a product UVA SUNSCREENS Although benzophe- Many of the organic chemicals com- in a scientific, peer-reviewed journal nones are primarily UVB absorbers, oxy- monly used in sunscreen products have independent of the manufacture’s data. benzone absorbs through UVA, making not been tested for long-term safety. For At a minimum, dermatologists should it a broad-spectrum absorber. It signifi- example, titanium dioxide– and zinc determine whether an ingredient has cantly augments UVB protection when oxide–based sunscreens have been pro- been shown to penetrate the skin and used in a given formula. The anthrani- moted on the assumption that they are whether the proposed effects have been lates are weak UVB filters that absorb less harmful than organic sunscreen documented histologically, biochemi- mainly in the near-UVA portion of the absorbers. However, the use of titanium cally, or at the molecular level. In partic- spectrum, making them less effective dioxide as a sunscreen also has no long- ular, dermatologists should warn than benzophenones. Butyl methoxy- term safety data.33 patients that encouraging data from in dibenzoylmethane provides superior There is a growing interest in botani- vitro studies might prove irrelevant if an protection through a greater portion of cals for sun protection, and research has agent fails to penetrate human skin.35 the UVA range. Although it is a signifi- found that some plant oils contain natural The first generation of antiaging cosmet- cant addition to true broad-spectrum sunscreens. For example, sesame oil ics, mostly antioxidants, has been fol- UV protection, concerns have been resists 30% of UV rays, whereas coconut, lowed by a second generation of antiag- 24 raised regarding its photostability and peanut, olive, and cottonseed oils block ing cosmetics comprised mainly of MCGH053-C70_[18-29].qxd 09/09/2008 05:05 AM Page 25 Aptara (PPG-Quark) tration, AHAs can be used as peeling effects of psoriasis and erythema and TABLE 70-6 agents.37 Elsewhere, glycolic acid was may help in reducing the risk of skin Partial List of Cosmeceutical Agents4 demonstrated to be effective for treating cancer. Vitamin E also has been shown First-Generation Cosmeceuticals pseudofolliculitis barbae,39 and salicylic to help in the reduction of scarring from Vitamin A (retinoids, retinoic acid, retinol) acid has been successful in treating wounds and to help reduce the appear- Vitamins C, B, E hyperkeratosis.36,39–42 ance of stretch marks.35 Coenzyme Q10 Unlike true keratolytics, AHAs exert Vitamin E acetate is often used instead Idebenone influence at lower, newly forming levels of vitamin E in skin care products -Lipoic acid of the SC.36 Many patients experience because it lacks the free phenolic Grape seed extract irritation from using products contain- hydroxyl group. However, vitamin E Green tea ing AHAs. While prescription and OTC acetate is biologically inactive. Despite Superoxide dismutase products differ only in pH and concen- this, the addition of vitamin E acetate to tration, studies have shown that efficacy skin care products appears to protect Second-Generation Cosmeceuticals depends more on pH than on concentra- skin against the harmful affects of sun- Copper peptides (Cu glycyl-L-histidyl- tion.38 Chemical peels have nearly all light after topical application. This is so L-lysine) been replaced with AHA-containing because vitamin E acetate is a provita- Growth factor-containing preparations: products.37 min that is converted to the active vita- CHAPTER 70 ■ COSMETIC PRODUCTS TNS Recovery Complex min by hydrolysis in the skin.49 4% Skin Growth Factor from placental Recently, Nakayama found that - extract Skin Supplements and Nutrients tocopherol-6-O-phosphate provided Recombinant EGF VITAMIN C Since skin uses endogenous protection against UVB-induced damage Recombinant TGF- 1 antioxidants to protect itself from pho- in cultured mouse skin. In the study, Pal-KTTKS (palmitoyl pentapeptide) todamage, the potential to use cosmet- which compared -tocopherol-6-O- ics containing antioxidants for addi- phosphate with -tocopherol acetate, tional protection is not unexpected.43 the water-soluble provitamin E provided Antioxidants applied topically have greater protection that -tocopherol growth factors4 (Table 70-6). Experts are been shown to be effective in stabiliz- acetate against sunburn cell formation, now evaluating the use of hormone ing free radicals on the skin, but absolute DNA degradation, and lipid peroxida- therapy in skin care products,35 for proof as to the clinical value has not yet tion.50 example, synethetic peptides such as been provided.44 Because proof is still Argireline to relax muscle and dimethy- lacking, the FDA limits the labeling of -LIPOIC ACID -Lipoic acid is a natu- laminoethanol (DMAE) to reduce fine cosmetics to only the chemical name— rally occurring dithiol compound known lines and wrinkles. for instance, ascorbic acid instead of vit- as an essential cofactor for mitochondrial amin C—so that consumers do not auto- energy production via the citric acid matically assume that a cosmetic will cycle.51,52 -Lipoic acid scavenges Exfoliants provide the commonly understood ben- hydroxyl radicals, singlet oxygen, and AHAs are naturally occurring organic efits of vitamin C taken orally.45 nitric oxide and has been afforded carbolic acids found in numerous cos- Vitamin C is a free-radical scavenger “superantioxidant” status because it is metics. AHAs are found in food sources, and a cofactor for the hydroxylation of both water- and lipid-soluble.53 To direct including fruit, sour milk, molasses, procollagen. In addition, pretreatment antioxidant activity, -lipoic acid pro- honey, and sugar cane, and can be syn- with vitamin C has been shown to tects vitamins E and C and downregu- thesized as well.36 Glycolic acid and lac- reduce sunburn cells in porcine and lates the transcription factor NF B.53 In tic acid are the two most common human skin exposed to UV light. As an addition, the powerful antioxidant pre- AHAs used in cosmetics, although many ascorbic acid, vitamin C is very unstable, vents lipid peroxidation in the cell mem- others are used in combination.37 AHAs causing manufacturers often to replace it brane by reducing glutathione.54 diminish skin scales (exfoliate), remove with ascorbyl palmitate. However, only -Lipoic acid is under investigation excess skin oil, and moisturize the skin. L-ascorbic acid significantly increases as a possible agent to treat pathophysi- In addition, studies suggest that AHAs vitamin C levels in the skin. Very few ologies of many chronic diseases. It and -hydroxy acids (BHAs) also may human studies have demonstrated the improves polyneuropathies and glycemic assist in the rejuvenation of photodam- potential photoprotective properties of control in association with diabetes and aged skin.36–38 These compounds reduce vitamin C.46 However, a few studies are mitigates toxicities of heavy metals.51 In corneocyte cohesion by modulating the worth noting. Vitamin C was shown to vitro studies have shown -lipoic acid to secretion of cytokine- and keratinocyte- reduce wrinkling in a double-blind, have anti-inflammatory properties. It derived growth factors, possibly leading vehicle-controlled clinical investigation has recently become a popular additive to the disruption of ionic bonds between with 19 participants.35 In addition, a in cosmetics designed to treat benign corneocytes. AHAs reduce skin thick- recent 6-month double-blinded, ran- photodamage.54 However, only limited ness, resulting in greater flexibility of the domized trial showed a highly signifi- data on efficacy are available. Although skin and reduced cracking and fissuring cant increase in the density of skin -hydroxy acid has been shown to pen- at the skin surface.36,39 microrelief and a decrease in furrows.47 etrate into subcutaneous tissues,55 prop- Although AHAs initially gained inter- erly designed clinical trials are still est in skin therapy because of the capac- VITAMIN E Vitamin E is a well-known needed to demonstrate the efficacy of ity to treat ichthyosis, the use of AHAs antioxidant that contains mixed toco- manufacturers’ claims.52 dates back to ancient times, when wine pherols, a class of very strong antioxi- and sour milk were sometimes used to dants.48 Many studies have shown that COENZYME Q10 Reactive oxygen species, rejuvenate skin.36 At the proper concen- vitamin E can help to decrease the formed in the mitochondrial respiratory 25 MCGH053-C70_[18-29].qxd 09/09/2008 05:05 AM Page 26 Aptara (PPG-Quark) chain, have been implicated in a number in vitro and in vivo studies using plants, SC to stimulate collagen production. of diseases and in the natural aging cultured human skin cells, and fruit Large clinical studies are still needed.4 process.56 Coenzyme Q10 (ubiquinone, flies.59,60 Unfortunately, there are only a CoQ10) is a naturally occurring antioxi- limited number of studies testing its effi- GREEN TEA Green tea contains polyphe- dant that quenches free-radical forma- cacy in humans. The studies in humans, nols known to have superior antioxidant tion in the mitochondria. Coenzyme sponsored by manufacturers of furfury- activity.66 In cosmetic science, the term Q10 originally gained interest as a ladenine, have indicated that furfurylade- green tea does not refer to common potential cancer treatment when investi- nine may be equivalent or superior in herbal tea. Instead, green tea refers to the gators discovered that cancer patients effectiveness to Retin A. Manufacturers product of a careful process in which the experienced reduced levels of the also reported that treatment with fur- leaves of the plant Camellia sinensis are enzyme. Although initial studies of furyladenine produced few side effects.61 processed, taking care to avoid oxida- using CoQ10 as a potential cancer treat- tion and polymerization of the polyphe- ment were encouraging, well-designed COPPER PEPTIDES The role of copper in nolic components. In green tea, the most studies with definitive results are still stimulating angiogenesis has been powerful of these polyphenols is (–)-epi- lacking.57 acknowledged for over two decades, gallocatechin-3-gallate (EGCG).66 Investigation of CoQ10 in treating and copper peptides have exhibited der- Preclinical studies in mouse models human skin conditions also has been mal wound-healing properties in several have provided evidence that green tea DERMATOLOGY FOR SKIN OF COLOR promising. In vitro studies found that studies.62,63 For example, copper sulfate polyphenols provide protection against topical CoQ10 reduced UV-induced induced expression of vascular endothe- UVB-induced immunosuppression and expression of collagenase in cultured lial growth factor (VEGF) in primary and the generation of reactive oxygen species. fibroblasts and provided antioxidant transformed human keratinocytes, and Topical application to mice demonstrated activity in human skin. In addition, a topical copper sulfate accelerated wound protection against several tumorigenic small 6-month controlled trial found a healing in murine dermal skin.64 Copper agents and was associated with the inhi- modest improvement in periorbital lines peptides have been shown to (1) stimu- bition of several biochemical markers of following 10 weeks of treatment with late collagen63 and elastin4 formation, (2) chemical carcinogenesis. In other studies, twice-daily topical CoQ10.4 stimulate the formation of glycosamino- topical application to both mice skin and glycans,65 (3) increase blood vessel for- human skin demonstrated that green tea IDEBENONE Idebenone is a short-chain mation and oxygenation within the may have the potential to reduce UV- biosynthetic analogue of CoQ10 con- skin,64 and (4) provide potent antioxidant induced oxidative stress-mediated skin taining the antioxidant properties of protection.4 diseases in humans.66 CoQ10 but with greater capacity to Important studies include a well- Recent reports also suggest that quench free-radical generation.56 The designed 12-week study that demon- EGCG reactivates dying cells. According drug was developed originally for the strated increased skin density in 67 to Dr. Stephen Hsu, old skin cells found treatment of cerebral ischemia–induced patients. Copper peptides also have in the upper layer of the skin appear to lesions. However, the results of treating enhanced healing of postoperative start dividing after exposure to EGCG. It neurologic disease with idebenone have wounds and diabetic foot ulcers.4 also was reported that exposure to not been encouraging.58 EGCG accelerates the differentiation The potential for using idebenone to GROWTH FACTORS Growth factors, process among new cells.67 treat skin conditions has been demon- important in wound healing, are present Liao and Hiipakka68 have shown that strated in several in vitro and in vivo in a number of cosmeceuticals. Among green tea polyphenols are potent studies and at least one clinical study. In the growth factors found in new cosme- inhibitors of type 1,5- -reductase, sug- an assay designed to screen for potential ceutical products, trandforming growth gesting the potential use of green tea treatments of common neurodegenera- factor (TGF- ) is the most important polyphenols in the treatment of andro- tive disorders—involving reactive radi- collagen-stimulating growth factor. TNS gen-mediated skin disorders such as cals and oxidative stress—idebenone Recovery Complex by SkinMedica is a androgenetic alopecia. provided protection from endogenous tissue-repairing complex containing Presently, numerous products are sup- oxidative stress in skin fibroblasts derived growth factors derived from cultured plemented with green tea, even though from Friedreich ataxia patients.58 In addi- fibroblasts of neonatal foreskin. The the concentration of active polyphenols tion, in vitro studies indicated greater growth factors contained in TNS in these products is unknown, and con- antioxidant capacity, compared with Recovery Complex help to repair sun- trolled clinical trials have not been con- CoQ10, vitamins E and C, kinetin, and - damaged skin by stimulating the epi- ducted.66 lipoic acid. Moreover, clinical photographs dermal thickening and deposition of showed an appreciable improvement in collagen. TNS Recovery Complex also GRAPE SEED EXTRACT Grape seed extract periorbital lines, and immunostaining con- contains antioxidants, matrix proteins, contains polyphenols, mainly flavonoids, [Au3] firmed downregulation of MMP expres- and soluble collagens.4 including oligomeric proanthocyanidins sion.4 Efficacy of the product has been (OPCs), which have antioxidant capabili- demonstrated in a single small study ties 20 times greater than vitamin E and 50 FURFURYLADENINE N6-Furfuryladenine is conducted by the manufacturer, in times greater than vitamin C.69,70 Studies a plant-derived growth hormone known which 79% of patients showed clinical suggest that grape seed extract binds to to have senescence-retarding effects in improvement, as measured by optimal collagen, where its antioxidant effects plants.59 This cytokinin’s antiaging prophylimetry and investigator grading.4 promote youthful skin, elasticity, and effects—notably, antioxidant properties However, significant questions exist flexibility.71 Studies also show that OPCs protecting DNA and protein from oxida- about whether these large molecules help to protect the body from several age- tive and a glycoxidative damage—have cross the SC and whether it is even nec- related diseases, including cardiovascular 26 been demonstrated effectively in several essary for these molecules to cross the disease and cancer.71,72 MCGH053-C70_[18-29].qxd 09/09/2008 05:05 AM Page 27 Aptara (PPG-Quark) in skin care, and current research is suc- TABLE 70-7 cessfully uncovering the mechanisms Plant Derivatives for Cosmetic Use75 behind these skin care applications. SKIN CARE PROPERTY PLANT DERIVATIVE Potential applications include (1) provid- Astringent Witch hazel, Hawthorne ing oil control, (2) providing moisturiza- Emollient Allman oil, hazelnut oil, sesame oil, wheat germ oil tion, (3) delaying hair regrowth, (4) Moisturizer Aloe vera, jojoba, Shea butter enhancing skin elasticity, and (5) reduc- Refreshing Camphor, hypericum, cypress ing the appearance of pigmentation and Softening Geranium, licorice UV-induced erythema and pigmenta- Soothing Aloe vera, avocado oil, chamomile (bisabolol), Linden ﬂower, lotus, seaweed tion.82,83 Toner Elder, horsetail, marjoram, sage Scientists have determined that small Miscellaneous: soybean proteins [soybean trypsin Decreases skin edema Marigold inhibitor (STI) and Bowman Birk Anti-irritant Allantoin inhibitor (BBI)] can reduce hyperpig- Strengthens nails Myrrh mentation through regulation of the protease-activated receptor 2 (PAR-2) pathway.84 Cosmetic formulations con- CHAPTER 70 ■ COSMETIC PRODUCTS taining these proteins have been shown OPC flavonoids have been shown to nence of retinol in consumer skin care clinically to help even out skin tone and strengthen and repair connective tis- products should not be viewed without smooth skin texture.82,83 sue.71 Grape seed extract may aid substantial attention to the differences Cosmetic scientists also found that a wound healing in two ways. Studies between prescription-strength retinoids natural soy formulation could effec- show that grape seed extract helps the and retinols in consumer skin care prod- tively reduce the appearance of body make more VEGF for angiogenesis ucts. Topical retinoids are prescription- unwanted facial hair above the upper lip to regenerate damaged blood vessels, strength drugs with the ability to help area while improving the overall skin and it also decreases the amount of free normalize hyperkeratinization and pro- appearance and skin condition.85 radicals in the wound site.71,73 vide anti-inflammatory effects. In con- trast, all-trans-retinol is a parent form of The Future of Cosmeceuticals PEPTIDES Oligo-, penta- and hexapep- vitamin A and has limited efficacy.76 tides such as retinoids improve the Some experts propose that the benefits One of latest technologies in develop- appearance of photodamaged skin by of the parent form of retinol are due to ment is the use of spin traps. These are stimulating collagen production, result- the oxidation of all-trans-retinol to the the very newest antioxidants, which ing in thickening of the skin. Palmitoyl active retinoid after absorption into skin catch or trap an aberrant electron as it pentapeptide (pal-KTTS) is a procolla- cells.77 Retinol is present in consumer starts to spin out of control and returns it gen pentapeptide fragment showing skin care products in widely varying cat- to its orbit before it can do any damage. efficacy in several well-designed studies egories. Some retinol products are effi- Although the use of spin traps in derma- for improving photoaged skin, including cacious,78 some are present below clini- tology is in its infancy, these compounds wrinkle appearance, age spots, and skin cally effective concentrations,4 and other have shown a great deal of promise in firmness. Histologic assessments in consumer skin care products contain the field of dermatology.86 studies showed positive changes to biologically inactive retinol forms.79 Spin traps were used originally as a elastin and collagen IV.74 In addition, However, the lower concentrations way to measure free-radical activity palmitoyl pentapeptide was comparable make these products less irritating than both in vivo and in vitro through their with significantly higher concentrations prescription-strength retinoids. Retinol ability to form stable complexes. The of retinol in reducing fine lines and wrin- has been combined with other products, most well-known spin trap is phenyl kles and improving hyperpigmentation including AHAs, to improve results.4 butyl nitrone (PBN).86 and dark circles. The pentapeptide was Topical all-trans-retinoic acid protects less irritating, did not cause redness or the skin against damage from UVA and CONCLUSION barrier damage, and had no effect on UVB rays by facilitating the ability to TEWL.4 prevent collagen loss and the ability to The cosmetic industry is an ever-chang- stimulate new collagen formation ing, ever-growing market that promises BOTANICALS It is likely that plant- within the capillary dermis of sun- to continue providing novel agents for derived ingredients were among the exposed skin.80,81 These protective prop- maintaining healthy skin. The true clini- very first cosmetics. Ingredients used erties form the basis for its use in mini- cal efficacy of some of these products since ancient times include colorants, mizing the appearance of fine wrinkle remains to be proven. However, many plant juices (for soothing and protection lines. products are known to provide clinically from insects), and fragrant oils. Several relevant results. In time, clinical efficacy plant derivatives are purported to have NEW AND INNOVATIVE APPLICATIONS FOR and safety data will be supplied. various skin care properties, as seen in SOY IN SKIN CARE The soybean, with its The development and tremendous Table 70-7.75 Caution must be observed broad spectrum of components, includ- growth in cosmeceutical sales are a because plants can cause serious allergic ing proteins, essential fatty acids, phy- response to consumer demands for reactions in certain individuals.54 tosterols, isoflavonoids, lecithins, and more scientific and sophisticated cos- saponins, has long been known to have metic products. The first generation of RETINOLS In 2004, retinol was report- skin care benefits from its use in tradi- cosmeceuticals provided supplements edly a component of at least 60 cosme- tional Chinese medicine. Scientists have and antioxidants. The second genera- ceutical products.4 However, the promi- identified several possible applications tion of cosmeceuticals focused on 27 MCGH053-C70_[18-29].qxd 09/09/2008 05:05 AM Page 28 Aptara (PPG-Quark) growth factors to help stimulate repair 18. Lewis C. Clearing up cosmetic confu- 38. Vidt DG, Bergfeld WF. Cosmetic use of of photoaged skin. While the twentieth sion. FDA Consumer, May-June 1998. alpha-hydroxy acids. Cleve Clin J Med Available at www.fda.gov/fdac/features/ 1997;64:327-329. century brought the development of 1998/398_cosm.html; accessed September 39. Perricone NV. Treatment of pseudofolli- cosmeceuticals, the twenty-first cen- 20, 2004. culitis barbae with topical glycolic acid: tury will mark the introduction of new 19. FDA. Fragrance free and unscented. U.S. A report of two studies. Cutis 1993;52: skin care technology in the form of Food and Drug Administration, May 232-235. Cosmoleculars—designer molecules in 1995. Available at http://vm.cfsan.fda.gov; 40. 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