Development and Clinical Assessment of a Comprehensive Product for Pigmentation Control in Multiple Ethnic Populations
December 2016 | Volume 15 | Issue 12 | Original Article | 1562 | Copyright © 2016
Elizabeth T. Makino BS CCRA MBA,a Kuniko Kadoya PhD,a Monya L. Sigler PhD,b Peter D. Hino MD FAAD,b and Rahul C. Mehta PhDa
aSkinMedica, Inc., An Allergan Company, Irvine, CA bThomas J. Stephens & Associates, Inc., Richardson,TX
BACKGROUND: Pigmentary changes in people of different ethnic origins are controlled by slight variations in key biological pathways leading to different outcomes from the same treatment. It is important to develop and test products for desired outcomes in varying ethnic populations. OBJECTIVES: To develop a comprehensive product (LYT2) that affects all major biological pathways controlling pigmentation and test for clinical efficacy and safety in different ethnic populations. METHODS: A thorough analysis of biological pathways was used to identify ingredient combinations for LYT2 that provided optimal melanin reduction in a 3-D skin model. Expression of four key genes for melanogenesis, TYR, TYRP-1, DCT, and MITF was analyzed by qPCR. Clinical study was conducted to compare the efficacy and tolerability of LYT2 against 4% hydroquinone (HQ). RESULTS: Average melanin suppression by LYT2 in 7 independent experiments was 45%. All four key genes show significant down- regulation of expression. LYT2 provided statistically significant reductions in mean overall hyperpigmentation grades as early as week 2 compared to baseline, with continued significant improvements through week 12 in all ethnic groups tested. CONCLUSION: We have successfully combined management of 6 categories of pathways related to melanogenesis: melanocyte activation, melanosome development, melanin production, melanin distribution, keratinocyte turnover, and barrier function to create a comprehensive HQ-free product. The outcome clearly shows greater pigmentation control with LYT2 compared to other HQ-free products in skin tissue models and earlier control in clinical studies compared to 4% HQ. Clinical study shows pigmentation control benefits of LYT2 in people of Caucasian, Hispanic, and African ethnic origins. J Drugs Dermatol. 2016;15(12):1562-1570.
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Skin conditions related to hyperpigmentation continue to contribute to psychosocial anxiety that leads to poor quality-of-life measures.1,2 Pigmentary changes are the first sign of aging in a majority of population, and they are self-described by patients using various expressions including dark spots, blotches, scars, dirty skin, stains etc. The desired outcome of pigment correction in these patients is to obtain skin with homogeneous pigmentation. In some cultures, dark skin represents a lower socioeconomic status, encouraging people to seek skin bleaching options for otherwise normal healthy skin. Regardless of the reasons, pigment correction remains one of the most sought after goals of aesthetic treatments worldwide. Melanin, in various forms and distribution pattern, is the primary pigment responsible for constitutive human skin color.3 It is synthesized by melanocytes at the base of the epidermis and transported to keratinocytes via dendrites using a series of complex steps. One of the primary functions of epidermal melanin is to provide protection against the constant onslaught of solar radiation. More than 375 different genes involved in pigmentation processes have been identified to date, and research is underway to further understand their role.4 In order to create a product to address the multitude of skin hyperpigmentation issues, it is important to understand the chemistry, biology, and genetics of melanin production and distribution in all ethnicities, which would allow rational combination of ingredients for correcting a wide range of pigmentary conditions.
Keratinocytes, melanocytes and broblasts secrete a number of cytokines in response to environmental damage and stress. α-Melanocyte stimulating hormone (αMSH)/ melanocortin 1 receptor (MC1R); endothelin-1 (ET-1)/ Endothelin B receptor (ET-B); and stem cell factor (SCF)/ c-KIT receptor, have been shown to substantially contribute to melanogenesis. Overexpression of these key markers is consistently observed in hyperpigmented skin compared to even-toned skin.5 Proopiomelanocortin (POMC), is a precursor of αMSH6 which binds to MC1R causing up-regulation of microphthalmia transcription factor (MITF). MITF functions