J. Cosmet. Sci., 63, 1–13 (January/February 2012) 1 Panthenyl triacetate transformation, stimulation of metabolic pathways, and wound-healing properties in the human skin GIORGIO DELL’ACQUA and KUNO SCHWEIKERT, Induchem AG, Industriestrasse 8a, CH-8604, Volketswil, Switzerland. Accepted for publication August 8, 2011. Presented in part as a scientifi c poster at the Annual Scientifi c Meeting and Technology Showcase of the Society of Cosmetic Chemists, New York, December 10–11, 2009. Synopsis Vitamin B5 and its derivatives are well known in personal care applications and are often used in wound healing and soothing compositions. However, little is known about the biochemical pathways involved. A better knowledge of these pathways would help to understand some of the mechanisms of action and suggest further applications. We have investigated the transformation of D-panthenyl triacetate (PTA) into D-panthenol (PAN) and its skin diffusion on human volunteers by Raman spectroscopy. Additionally, we have utilized human skin biopsies and quantitative RT-PCR to demonstrate the effect of PTA compared to PAN on 27 metabolic markers when introduced at 2% in a cosmetic emulsion. Then we conducted a double- blind clinical study to measure the effect of PTA compared to PAN on wound healing, measured by transepi- dermal water loss (TEWL), when incorporated at 3% in a cosmetic emulsion. Results show de-acetylation of PTA into PAN and an increased activity of PTA compared to PNA over time in the skin. Metabolic marker analysis demonstrates stimulation of energetic pathways such as glycolysis and the citric acid cycle, but also of synthesis pathways such as isoprenoids and lipid synthesis, by PTA and PAN. Finally, the clinical study demonstrates a statistically signifi cant effect by PTA on wound healing after 72 hours when compared to a saline treatment. Statistical signifi cance was not achieved by PAN or a placebo treatment. Due to the differ- ences between PTA and PAN action, different applications in personal care products can be suggested. More- over, PTA seems more effective than PAN for a long-lasting wound healing action. INTRODUCTION D-panthenyl triacetate (PTA) is a derivative of D-panthenol (PAN) and a precursor of panthotenic acid. Pantothenic acid is essential to normal epithelial function. It is part of coenzyme A, which serves as a cofactor for a variety of enzymatic reactions that are impor- tant in the metabolism of carbohydrates, fatty acids, and proteins (Figure 1). PAN, being the stable alcoholic analog of pantothenic acid with good skin penetration, has several properties in topical skin applications. Early literature in the 1950s demonstrated its function as a healing ingredient in cutaneous wounds (2). As dexpanthenol, its use in treating various types of dermatoses, such as atopic dermatitis, and as a natural alternative to Address all correspondence to Giorgio Dell’Acqua at giorgio.dellacqua@induchem.com.

JOURNAL OF COSMETIC SCIENCE 2 topical corticosteroids, has been extensively studied (1,3). Furthermore, its predominant role as a strong anti-irritant and its ability to protect and rebuild the skin barrier through the stimulation of barrier lipid synthesis has been suggested by several studies (4–7). The capacity of PAN to repair the skin barrier has also been postulated as a possible way for PTA to normalize sebum release by strengthening the follicular barrier in persons with oily skin (8). Although several clinical studies on the effi cacy of PAN are available, very little is known on the biochemical mechanism involved. In the context of wound healing, a study on fi broblasts has shown the capacity of PAN to increase protein synthesis and release (9). Interestingly, PAN and PTA have shown the capacity to protect skin from UV-induced erythema (1 G. Dell’Acqua, unpublished data), and data on in vitro and on human skin explants have shown that both PAN and PTA would stimulate the proteins involved into UV-induced oxidation protection and repair (10–12). Taken together, these data suggest that an array of genes could be stimulated by PAN and PTA. Recently, re- search on proliferating fi broblasts in connection with wound healing has shown the acti- vation of genes such as IL-6, IL-8, and HMOX-1 by calcium pantothenate (13), while studies on normal human keratinocytes in connection with an infl ammatory profi le have shown the capacity of PTA in combination with fl avonoids to inhibit a series of pro- infl ammatory genes (7). In order to better understand the underlying molecular mechanism of PTA, we have de- cided to investigate the activation of several biochemical markers in human skin explants when treated with PTA at 2% in an emulsion. We have compared these data with D-panthenol (PAN) in the same condition. We have verifi ed in vivo that PTA penetrates the stratum corneum and that it is de-acetylated in PAN. We have, fi nally, analyzed the wound-healing properties of PTA compared to PAN when applied on the skin by measur- ing the transepidermal water loss (TEWL) of human volunteers who have been subjected to suction blisters. Figure 1. Carbohydrates, fats, and lipid metabolism summary. D-panthenyl triacetate is a derivative of D-panthenol and pantothenic acid, a component of acetyl CoA.