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                                      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

                                         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-
                                                                                       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
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        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-
        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
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                                      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-

                                      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,
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        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
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                                      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

                                      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
                                      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-
                                      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
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                                                                                                              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
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                                                                                                                                   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,

                                       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
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                                                          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
                                                          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
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                                             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

                                             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
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                                                                                                               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
        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
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        [Au1]AU: Spell out.
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        [Au4]AU: Supply vol. no.
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