Journal of Clinical and Aesthetic Dermatology

MAY 2018

An evidence-based, peer-reviewed journal for practicing clinicians in the field of dermatology

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32 JCAD JOURNAL OF CLINICAL AND AESTHETIC DERMATOLOGY May 2018 • Volume 11 • Number 5 O R I G I N A L R E S E A R C H weeks of the study, the water content increased steadily as the dry skin condition resolved. The baseline median corneometry reading of 50.00 increased to 70.00 by Week 2 and 80.00 by Week 4, both representing a significant (p<0.0001) increase in skin water content. Conversely, the TEWL reading decreased at Week 2 and Week 4 as the barrier improved and approached significance at four weeks (p=0.0363). DISCUSSION Use of the ceramide cream in this study resulted in a 100-percent improvement in IGA scores and a 67-percent improvement in overall subject skin self-assessment scores after four weeks of use in individuals with atopic dermatitis or other sensitive skin conditions. Improvements were statistically significant. Typically, these skin conditions are treated with topical corticosteroids. The study cream used herein was a unique formulation of several ingredients with different mechanisms of action relevant to the improvement of sensitive skin. Such a cream could be combined with prescription therapy, used alone in cases of more minor disease, or used solely during the maintenance phase following treatment. Subjects with mild-to-moderate atopic dermatitis or other dermatoses associated with sensitive skin conditions were enrolled in the present study to examine the abilities of the cream to function beyond simple cosmetic moisturization. The formulation utilized dimethicone and petrolatum as occlusive moisturizers to create a temporary skin barrier in combination with glycerin as a humectant to attract and hold water in the stratum corneum and epidermis. The active ingredients included ceramide PC-104, palmitamide MEA, glycerrhetinic acid, and grape seed extract. It is worthwhile to examine how this combination of ingredients resulted in sensitive skin improvement. Ceramide PC-104, with the corresponding chemical name N-(3-hexadecyloxy-2-hydroxypropyl)-N-2- hydroxyethyl hexadecanamide, is a synthetic pseudoceramide developed to allow higher concentrations of ceramides to be used in skin care products free of contaminants, as many natural ceramides are derived from bovine sources. 6 Topical pseudoceramides have been shown to decrease improved stratum corneum water- holding properties and facilitate barrier repair, which is important in sensitive skin conditions. 7,8 The second need of a sensitive skin cream is to reduce inflammation reduction and accompanying itch. Palmitoylethanolamine (PEA), also known as palmitamide MEA, belongs to the family of N-acylethanolamines. Cells naturally produce these substances in order to down-regulate the inflammatory response via cannabinomimetic action on cannabinoid (CB) receptors. 9 This observation has led to postulation that this family of molecules might possess analgesic, antioxidant, and anti- inflammatory skin benefits. 10 CB 1 receptors are found in the brain and peripheral tissues, while CB 2 receptors are distributed throughout the immune system and in cutaneous nerve fibers. 11 CB receptor agonists, such as PEA, reduced histamine-induced itch and vasodilation when applied topically prior to histamine. 12 The third need of sensitive skin is inflammation reduction. The study formulation included grape seed extract, which contains the antioxidants proanthocyanidin and polyphenol, as well as a licorice extract containing glycerrhetinic acid for this purpose. Proanthocyanidin possesses antioxidant free radical neutralizing effects 20 times more potent than vitamin C and 50 times more potent than vitamin E. 13 CONCLUSIONS The combination of ceramide PC-104, palmitamide MEA, glycerrhetinic acid, and grape seed extract in a glycerin, dimethicone, petrolatum vehicle resulted in the concurrence between the investigator, subject, and noninvasive assessments for successful improvement of the signs and symptoms of mild-to-moderate atopic dermatitis and other xerotic or pruritic dermatoses in both pediatric and adult populations. REFERENCES 1. Di Nardo A, Wertz P, Giannetti A, Seidenari S. Ceramide and cholesterol composition of the skin of patients with atopic dermatitis. Acta Derm Venereol. 1998;78(1):27–30. 2. Vielhaber G, Lange S, Ley J, Koch O. N-palmitoyl- 4-hydroxy-L-proline palmityl ester: a pseudoceramide that provides efficient skin barrier repair and protection. Int J Cosmet Sci. 2006;28(1):70. 3. Hemmati AA, Foroozan M, Houshmand G, et al. The topical effect of grape seed extract 2% cream on surgery wound healing. Glob J Health Sci. 2014;7(3):52–58. 4. Veraldi S, De Micheli P, Schianchi R, Lunardon L. Treatment of pruritus in mild-to-moderate atopic dermatitis with a topical non-steroidal agent. J Drugs Dermatol. 2009;8(6):537–539. 5. Takiwaki H, Serup J. Measurement of color parameters of psoriatic plaques by narrow-band reflectance spectrophotometry and tristimulus colorimetry. Skin Pharmacol. 1994;7(3):145–150. 6. Mizushima H, Fukasawa J, Suzuki T. Phase behavior of artificial stratum corneum lipids containing a synthetic pseudo-ceramide: a study of the function of cholesterol. J Lipid Res. 1996;37(2):361–367. 7. Uchida Y, Holleran WM, Elias PM. On the effects of topical synthetic pseudoceramides: comparison of possible keratinocyte toxicities provoked by the pseudoceramides, PC104 and BIO391, and natural ceramides. J Dermatol Sci. 2008;51(1):37–43. 8. Park BD, Youm JK, Jeong SK, et al. The characterization of molecular organization of multilamellar emulsions containing pseudoceramide and type iii synthetic ceramide. J Invest Dermatol. 2003;121(4):794–801. 9. Noli C, Della Valle MF, Miolo A, et al. Efficacy of ultra-micronized palmitoylethanolamide in canine atopic dermatitis: an open-label multi-centre study. Vet Dermatol. 2015;26(6):432–440, e101. 10. Eberlein B, Eicke C, Reinhardt HW, Ring J. Adjuvant treatment of atopic eczema: assessment of an emollient containing N-palmitoylethanolamine (ATOPA study). J Eur Acad Dermatol Venereol. 2008;22(1):73–82. 11. Facci L, Toso RD, Romanello S, et al. Mast cells express a peripheral cannabinoid receptor with differential sensitivity to anandamide and palmitoylethanolamide. Proc Natl Acad Sci USA. 1995; 92(8):3376–3380. 12. Ständer S, Schmelz M, Metze D, et al. Distribution of cannabinoid receptor 1 (CB1) and 2 (CB2) on sensory nerve fibers and adnexal structures in human skin. J Dermatol Sci. 2005;38(3):177–188. 13. Nassiri-Asl, M., Hosseinzadeh, H. Review of the pharmacological effects of Vitis vinifera (grape) and its bioactive compounds. Phytother Res. 2009;23(9):1197–1204. JCAD

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