j. Soc. Cosmet. Chem., 47, 351-362 (November/December 1996) Lipo-amino acid cholesteryl derivatives promote recovery effect for damaged skin HIROJI ISHII, NAOKO MIKAMI, and KAZUTAMI SAKAMOTO, Ajinomoto Central Research Laboratories, Tokyo, Japan. Accepted for publication January 15, 1997. Synopsis The ability of cholesteryl derivatives to promote the recovery effect in skin damaged by sodium lauryl sulfate was investigated. Among cholesteryl derivatives, acylglutamic acid cholesteryl ester (AGCE) was shown to be effective, either by itself or as a substitute for ceramide (type III). Recovery was evaluated in vivo on human skin using dermal scores, water-holding capacity (conductance), and transepidermal water loss (TEWL). When substituted for ceramide in an artificial stratum corneum lipid model, AGCE also formed a lameliar structure. INTRODUCTION It is well known that the softness of the skin is related to its water content (1). Skin damage caused by external stimulation or irritation results in the destruction of the barrier function of the stratum corneum, which in turn reduces the water-holding capacity and water content of the skin (2,3). Skin characterized by a pathological stratum corneum, such as senile xerotic skin, also has a much lower water content than that of healthy skin (4). This marked decrease in the water-holding capacity of damaged skin is often accompanied by a selective loss of intercellular lipids in the stratum corneum (5). Thus, the use of intercellular lipids as emollients is increasing in recognition as a means of maintaining the softness and flexibility of skin. Stratum corneum lipids consist mainly of ceramides, cholesteryl esters, cholesterol, and fatty acids (6). Ceramides are reported to be the main components of the stratum corneum lipids, and to play an important role in promoting the water-holding capacity of skin by forming a lameliar structure that acts as a moisture evaporation barrier (5,7). Cholesterol and cholesteryl derivatives are also thought to be effective components in these lipid bilayers for retaining water and promoting the recovery of water-holding capacity in damaged skin (7). For example, it has been reported that stratum corneum lacking cholesterol and cholesteryl derivatives exhibits a decrease in its water content and high rates of skin disease (8). Although ceramides are recognized as the key com- 351

352 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS ponents in stratum comeurn lipids, they are difficult to incorporate into cosmetic products due to their poor solubility and high cost as raw materials. Acylglutamic acid cholesteryl esters (AGCEs) are cholesteryl derivatives synthesized from cholesterol and lipo-amino acid (lauroyl glutamic acid) they have a cholesterol group and exhibit a structural resemblance to ceramide. Therefore, the present study investigated the possibility of using cholesteryl derivatives including AGCEs as an alternative to ceramides. AGCEs and other cholesteryl derivatives were examined with respect to their ability to promote the recovery effect in skin damage induced by sodium lauryl sulfate (SLS). Recovery was evaluated in damaged skin using dermal scores, water-holding capacity (conductance), and transepidermal water loss (TEWL). The util- ity of these measures has already been demonstrated with subjective clinical assessment of the skin surface (9,10), the skin surface hygrometer (11), and the evaporimeter (12,13), respectively. Since AGCE is hypothesized to play a role similar to ceramide in the stratum corneum, we examined whether AGCE would be incorporated into the lameliar structure and thereby exert a water-holding capacity. In order to clarify this point, we composed an artificial stratum corneum lipid model containing either cer- amide (Model A) or AGCE (Model B) and examined the formation and arrangement of the resulting lameliar structure. The efficacy of models A and B in promoting the recovery of damaged skin was then verified in order to assess the possibility of using AGCE as a substitute for ceramide. EXPERIMENTAL MATERIALS SLS was obtained from Nikko Chemicals Company, Tokyo, Japan. Cholesteryl hydroxy stearate was obtained from Nisshin Oil Mills, Ltd., Tokyo, Japan. AGCEs were products of Ajinomoto Co., Inc., Tokyo, Japan. AGCE-202 is a mixed ester of cholesteryl/ octyldodecyl lauroyl glutamate. AGCE-301 is a mixed ester of cholesteryl/behenyl/ octyldodecyl lauroyl glutamate. Phosphatidyl ethanol amine, cholesterol sulfate, and ceramide (type III) were obtained from Sigma Chemical Co., St. Louis, MO. Petrolatum, pristane (2,6,10,14-tetramethyl pentadecane), squalene, myristic acid, oleic acid, pal- mitic acid, stearic acid, linoleic acid, and cholesterol were obtained from Junsei Chemi- cal Co., Ltd., Tokyo, Japan. Triolein was obtained from Tokyo Chemical Industries Co., Ltd., Tokyo, Japan. All materials were used without further purification. SUBJECTS Eight healthy male volunteers ranging in age from 24 to 29 years served as subjects. METHOD Induction of skin damage by 1% sodium lauryl sulfate (14,15) Skin damage was induced by applying 1 5 •1 of sodium lauryl sulfate (SLS) (1.0 wt % solution in deionized water) to the volar side of the forearm in a closed patch for 24 hours, using occlusive aluminum chambers (Finn-Chamber, Epitest, Helsinki, Finland)