Impure Skin: (Not) a Problem for Mature Skin? Cosmetics Combating Impure Skin

11-2013

English Edition International Journal for Applied Science • Personal Care • Detergents • Specialties

T. Clarius, B. Vogelgesang, N. Abdul-Malak, C. Reymermier, I. Bonnet Impure Skin: (Not) a Problem for Mature Skin? Cosmetics Combating impure skin

T. Clarius*, B. Vogelgesang, N. Abdul-Malak, C. Reymermier, I. Bonnet** Impure Skin: (Not) a Problem for Mature Skin?

■■Impure skin: More than a infants (acne infantum), for example, products and are willing to spend more cosmetic problem may also be affected by acne. Acne tarda money for it. The rather moderate form represents a very special area in cosmet- of acne tarda allows producers to of- Without doubt impure skin and acne ics and especially women in menopause fer and market milder products which are among the most emotional topics in may suffer from it. This type of acne in have a long-term, physiological effect. the cosmetics industry. Those who are adults is milder than that in adolescents. In contrast to products for adolescents it afflicted with it are often exposed to Nevertheless, it may present a large psy- is easier to create more comprehensive severe suffering. It is a major challenge chological burden for those concerned, series targeted at this group. Besides for cosmetic producers to offer efficient because they had hoped to have over- inhibiting the formation of dihydrotes- cosmetic solutions for this problem. come such problems after puberty. tosterones, products may refer to other Over decades, cosmetic producers have A growing number of cosmetic produc- approaches connected with impure skin, primarily been devoted to the young tar- ers is dedicated to this potential group including antibacterial, antioxidative or get group that suffers from acne dur- of customers. The reasons for this are moisturizing effects. In addition, it is ing puberty (acne vulgaris). However, obvious: Menopausal acne concerns possible to incorporate active ingre- acne can occur in almost all age groups. female consumers who are familiar dients which allow anti-aging claims. Newborns (acne neonatorum) and small with applying anti-aging and skin care Many manufacturers have done this for a long time, especially on the U.S. market. The doctor brand »Murad®« advertises an »anti-aging acne« series, Patricia Wexler M. D. offers an »anti- Abstract aging cleanser«, »Skin Refinish« (M2) is said to fight skin impurities on the one hand and wrinkles on the other, and n the past, manufacturers used to tailor cosmetic solutions targeting impure Jan Marini Skin Research™ promises skin and acne mainly to the needs of a young consumer group. However, to relieve the skin problems of adults Iacne can occur during almost all stages of life, including during menopause. which include acne tarda. The renowned Meanwhile, many cosmetic manufacturers have identified women suffering US brand proactiv® solution strives to from so-called menopausal acne as potential customers. Their high purchasing develop the European market for prod- power and their familiarity with the application and price ranges of anti-aging ucts treating impure skin. The proactiv® brand addresses idols of the younger or skin care products offer ample scope for the design of elaborate products. In target group such as US celebrities Jus- this article, BASF experts Torsten Clarius, Nabil Abdul-Malak, Corinne Reymer- tin Bieber and Julianne Hough. Inter- mier, Isabelle Bonnet and Boris Vogelgesang introduce innovative cosmetic ac- estingly, celebrities who are older than tive ingredient options for the formulation of skin care products that meet the thirty including Jennifer Love Hewitt various needs of this particular group of consumers. In the course of this, they and Vanessa Williams are featured in analyze the hormonal causes for impure skin in women during menopause and, advertisements of proactiv®. In Europe, Susan Sideropoulus (born 1980) and Re- on the basis of test results, demonstrate in great detail the performance of the gina Halmich (born 1976) are featured. cosmetic active ingredients presented. German producer Beiersdorf now addresses women »who long after puberty still have to fight impure skin« with its »Pure Effect« Nivea series.

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■■Causes for impure skin and acne

The sebaceous gland discharges into the hair follicle, an elongated invagi- nation on the epidermis, at the end lower of which hair is formed in the hair root. Sebocytes, specific cells in the sebaceous gland, produce sebum, which is pressed in a holocrine secretion into the duct when cells burst and are then pushed onto the skin through the follicle’s exit (Fig. 1) (1). There, sebum spreads in dependence of the skin’s hu- midity and environmental conditions. The sebum which is produced in the sebaceous glands contains various glyc- erides, wax ester, cholesterol, free fatty acids and squalene, etc (2). If too much sebum is produced, con- Fig. 1 Schematic representation of sebum production through activation of the glomerates and comedones may be DHT receptor formed which block the duct. An in- crease in horny cells (hyperkeratosis) may additionally inhibit the outward flow so that subsequently open and not covered by clothing. Thus, the fore- steroid-containing drugs may be con- closed comedones are formed. The mi- head, nose, cheeks, and chin (»t zone«) fronted with overly oily skin. Unsuitable cromilieu in the comedones and the as well as back, upper arms, legs and cosmetic products can also cause com- sebum presents ideal conditions for mi- scalp may be concerned (3). edones (4,5). Allergies and a hornifica- croorganisms. Propionibacteria release Milder forms of acne, including com- tion disorder of the hair follicle as well lipases which split fats and release fatty edonal acne, are suitable for cosmet- as a genetic disposition towards an in- acids which, on the other hand, trigger ic treatment. In more serious cases, creased production of sebum are among inflammatory reactions. Chemotacti- where, depending on the degree of skin the intrinsic causes. Nevertheless, it is cally effective substances such as cyto- changes and their state of inflamma- undisputed that the decisive factor is kine IL-1α and reactive oxygen species tion, papules, pustules and knots are of hormonal nature (6). Testosterone (ROS) also play a major role in these distinguished, cosmetic products may is metabolized by the 5α-reductase inflammatory processes. accompany a dermatological therapy. enzyme into a biologically even more Generally, acne may occur in all areas The causes of impure skin are of both effective dihydrotestosterone (DHT), of the skin which have many sebaceous extrinsic and intrinsic nature. Environ- which unfolds its efficacy via the an- glands. For the most part these unfor- mental factors or bacterial settlement drogenous receptor. DHT has a 50-fold tunately are the areas which are usually may play a role. Patients who take higher affinity to the androgenous re-

Fig. 2 Measurement of type 1α-reductase gene expression in normal human keratinocytes cultured in monoclayers

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ceptors of the sebaceous glands than at its peak prior to and during the first levels are significantly reduced. Hair testosterone. months of birth and then drastically loss may be a consequence; the skin decreases, and increases again at the becomes oilier whereas its dryness in- age of eight (8). The hydrophobic char- creases simultaneously. Scientists as- ■■Sebum: A relic which makes no acter of the sebum certainly increases sume that a major cause for increas- sense? the impermeability of the skin towards ing acne in women throughout the exterior influences. A decreased sebum past few years is the increasing bur- The physiological significance of se- production is, however, not a physi- den on women by work and the family. bum is disputed. Often, it is described ologic reaction to short-term exogenic Chronic stress leads to a certain level as a main component of the hydro- circumstances, as the sebum reaches of stress hormones in the body. They lipid films which control the barrier the skin surface only ten days after the have a slight rest androgenic effect function of the skin via TEWL and the synthesis (9). and attack the sebaceous glands at absorption of water (7). It is known the same receptor. that small infants have a particularly flawless skin although their sebaceous ■■The role of hormones glands are practically inactive. In fact, ■■Ways to fight impure skin the secretion of sebum is subject to In women, the climacteric period very strong fluctuations throughout starts at approximately the age of By using keratolytic or astringent life. The reasons for this are largely 35 and may vary individually. Slowly substances, many cosmetic ingredi- unknown. The production of sebum is but steadily, the hormonal balance ents which fight impure skin avoid and the hormone production of the the actual cause of acne. This lies in ovaries are reduced until menopause the hormone-regulated, increased starts between the ages of 40 to 55. sebum production. The major role The proportion of male hormones (an- here is assumed by DHT which is syn- drogens) is increased in relation to the thesized in the sebaceous glands by female hormones; resulting in a rela- catalysis of the membrane-attached tive hyperandrogeny, where the adre- 5α-reductase (10). Another factor is nal androgens have no counterparts. that 5α-reductase occurs in two iso- As early as at the beginning of the mers and that only 5α-reductase type hormonal fluctuations skin changes 1 is responsible for the sebum for- Fig. 3 N-methylglycin may appear; as a rule, they appear mation, whereas 5α-reductase type 2 at the age of 50 when the estrogen plays a role in hair loss (11). Therefore, the inhibition of 5α-reductase type 1 is the most promising approach to reducing the excess sebum production. However, only few specific inhibitors are known including zinc derivatives which are frequently incorporated in cosmetics. Their efficacy in terms of impure skin seems to be attributable to their anti-inflammatory proper- ties.

■■Identification of active ingredients via qRT-PCR

Our target was to identify a highly specific inhibitor of 5α-reductase type 1. Therefore, 100 potential candidates for active ingredients were tested on human keratinocyte cultures with the aid of qRT-PCR. The reference substance zinc gluconate reduced the expression Fig. 4 Conversion of testosterone to dihydrotestosterone in human skin explants in the of 5α-reductase type 1-gene by 58 % presences of 2 % Mat-XS™ Clinical when compared to the untreated control culture (Fig. 2).

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The test substance with the best result was N-methylglycine. Mat-XS™ Clini- cal is a solution of the amino acid N- methylglycine (Fig. 3), which was first identified by German chemist Justus von Liebig as »Sarkosine«. N-methylglycine which has a sweet taste occurs as an intermediate step in the choline and glycine metabolisms.

■■Ex vivo study

To prove the postulated effect mecha- nism, a study was conducted on human skin biopsies where the actual transformation of testosterone into dihydrotestosterone was determined. Here, zinc gluconate also served as reference substance. In the presence Fig. 5 Changes in the squalene content of sebum sampled with Sebutapes® after 28 of 2 % Mat-XS™ Clinical in the culture days of treatment with 2 % Mat-XS™ Clinical ( % T28/T0) medium, 36 % less DHT was formed (Fig. 4).

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Fig. 7 Self-evaluation of skin re-greasing by Caucasian and Fig. 6 Self-evaluation of oily appearance by Caucasian volun- Asian volunteers after 28 days of treatment with 2 % Mat- teers after 28 days of treatment with 2 % Mat-XS™Clinical XS™ Clinical

■■In vivo studies came oilier more slowly (Fig. 7). 88 % ■■Inhibition of DHT formation and stated a more regular complexion further suitable approaches In humans squalene exclusively oc- (Fig. 8). The pore size decreased by curs as a component of sebum. In this 20.5 % (Fig. 9). The oppression of the transformation of way, it may serve as a benchmark for The results obtained from the trial testosterone into dihydrotestosterone the synthesis activity of sebocytes. panel with Caucasian skin were com- is the decisive approach to combat skin Therefore, the squalene content of parable with those obtained from the impurities before and after menopause. sebum was measured with Sebutape™ Asian panel and confirm that Mat- However, it becomes possible to develop after a 4-week application period in XS™ Clinical is an excellent active in- series of skin care and conditioning prod- 25 test persons in vivo. In this study, gredient for combatting impure skin. ucts in a more comprehensive way. Mild 2 % Mat-XS™ Clinical decreased the squalene content in sebum by 19 % (Fig. 5).

■■Multicenter study in Thailand and France

In order to prove the expected effects of Mat-XS™ Clinical in vivo, a multicenter study was conducted in Bang- kok and Bordeaux including a total of 90 test persons with oily skin. The test products, light O/W emulsions, con- tained either 1 % zinc gluconate or 2 % Mat-XS™ Clinical and were applied twice daily throughout four weeks. The results were evaluated dermato- logically and with the aid of digital photos. In addition, the test persons were asked to state their perception in a questionnaire. Almost all test persons (96 %) of the French trial panel confirmed that their skin had a matter appearance Fig. 8 Self-evaluation of complexion evenness by Caucasian volunteers after 28 (Fig. 6). The same percentage of days of treatment with 2 % Mat-XS™ Clinical the panel stated that their skin be-

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Fig. 9 Clinical evaluation of pore size Caucasian volunteers after 28 days of treatment. Illustrative pictures taken under polarized light.

Fig. 10 Changes in mean improvement of pore density and volume for responding volunteers after 28 days of treatment with 0.4 or 3 % Beta-Hydroxyde™ ACSD

keratolytics such as a coupling product made between salicylic acid and polysac- charides from acacia (Beta-Hydroxyde™ ACSD) may help to open pores. By attach- ment to the highly molecular polymers, the penetration capacity of salicylic acid is reduced. Thus, an extended efficacy is obtained while reducing the irritation potential at the same time. An incorpo- ration at pH 7 allows particularly mild formulations. In a clinical study involving 100 test persons, the positive influence on the pore size could be demonstrated, etc. (Fig. 10, 11). Through excitement and release of β-defensins, the skin-inherent combat against bacteria, inflammation processes may be controlled in an elegant way. Here, Fig. 11 Image analysis of replicas illustrating the best improvement in pore volume an extract of wild mint, Peumus Boldus and density, before and after 28 days of treatment with Beta-Hydroxyde ACSD™ (Betapur™), is particularly suitable. A study including fifty test persons showed a sig-

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nificant improvement in the skin’s appear- (9) Estimation of sebum production rates in ance and a decrease in red spots (Fig. 12). man by measurement of the squalene con- Authors´ addresses: tent of skin biopsies, Downing DT, Stewart *Dr. Torsten Clarius, Main author ME, Strauss JS, The Journal of Investigative BASF Personal Care & Nutrition GmbH ■■Summary Dermatology, 1981, 77(4): 358-360. Rheinpromenade 1, 40789 Monheim Germany Combatting impure skin is a topic which (10) Four amino acid segment in steroid E-mail: [email protected] reaches a large number of consumers and 5α-reductase 1 confers sensitivity to Finas- which is by no means restricted to adoles- teride, a competitive inhibitor, Thigpenz AE, **Boris Vogelgesang cent consumers. Thus, women before and Russell DW, The Journal of Biological Chem- Nabil Abdul-Malak during menopause present a target group istry, 1992, 267 (12): 8577-8683. Corinne Reymermier for the industry who are not only inter- Isabelle Bonnet esting from a cosmetic point of view but (11) Immunolocalization of 5α-reductase iso- Coauthors also because of their purchasing power. The zymes in acne lesions and normal skin, BASF Beauty Care Solutions France S.A.S multitude of causes and accompanying fea- Thiboutot D, Bayne E, Thorne J, Gilliland K, 69366 Lyon, Cedex 07, France tures allow the formulation of care series Flanagan J, Shao Q, Light J, Helm K, Archives with a wide spectrum. An extensive range of of Dermatology, 2000, 136: 1125-1129. n specific active ingredients which have been tested on large panels is available to support the efficacy of formulations and which help to create products for specific purposes.

References

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(3) The sebaceous gland and acne – 40 years on, Cunliffe WJ, Dermatology, 1998, 196: 9-15

(4) A human model for assessing comedogenic substances, Mills OH Jr, Kligman AM, Arch Dermatol. 1982, 118(11): 903-5.

(5) A re-evaluation of the comedogenicity con- cept, Draelos ZD, DiNardo JC, J Am Acad Der- matol. 2006, 54(3): 507-12.

(6) Cutaneous androgen metabolism: basic research and clinical perspectives, Chen WC, Thiboutot D, Zouboulis CC, The Journal of In- vestigative Dermatology, 2002, 119: 992-1007.

(7) LXRα enhances lipid synthesis in SZ95 sebocytes, Hong I, Lee MH, Na TY, Zouboulis CC and Lee MO, The Journal of Investigative Dermatology, 2008, 128: 1266-1272.

(8) Regulation of human sebaceous glands, Fig. 12 Clinical evaluation of the occupation rate of red blotches and their color in- Thiboutot D, The Journal of Investigative tensity; digital photos for illustration after 28 days of treatment with Betapur™ 2 % Dermatology, 2004, 123: 1-12.

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