Marra Fabio, Ostacolo Carmine, Laneri Sonia, Bernardi Antonietta, Sacchi Antonia, Padula Cristina, Nicoli Sara, Santi Patrizia
Dipartimento Farmaceutico, University of Parma, Viale G.P. Usberti 27/A, 43100 Parma, Italy.
J Pharm Sci. 2009 Jul;98(7):2364-76. doi: 10.1002/jps.21608.
The aim of this work was to synthesize new pro-vitamins of alpha-tocopherol (VE) able to release another moiety such as an amino acid, in order to obtain a combined antioxidant and moisturizing effect upon topical application. The new derivatives were characterized and tested for sensitivity to chemical and enzymatic hydrolysis. Lipophilicity was estimated using Log capacity factor and skin retention was determined in vitro, using rabbit ear skin as barrier. Five molecules were synthesized using L-proline, L-serine, L-tyrosine, L-asparagine, and L-citrulline as amino acidic moiety. All pro-vitamins showed similar or lower lipophilicity than alpha-tocopheryl acetate (VEAc), taken as reference, and similar stability in aqueous solutions. All pro-vitamins showed to be sensitive to enzymatic hydrolysis. None of the pro-vitamins crossed the skin in significant amounts, whereas they accumulated into the skin, in both the dermis and the epidermis. They are more hydrophilic and more water-soluble than the currently used acetate.
这项工作的目的是合成新的α-生育酚（维生素E）前体维生素，使其能够释放出另一种成分，如氨基酸，以便在局部应用时获得抗氧化和保湿的综合效果。对新衍生物进行了表征，并测试了其对化学和酶促水解的敏感性。使用对数容量因子估计亲脂性，并以兔耳皮肤为屏障，在体外测定皮肤滞留率。使用L-脯氨酸、L-丝氨酸、L-酪氨酸、L-天冬酰胺和L-瓜氨酸作为氨基酸部分合成了五个分子。所有前体维生素的亲脂性均与作为参考的α-生育酚醋酸酯（VEAc）相似或更低，在水溶液中的稳定性也相似。所有前体维生素均显示对酶促水解敏感。没有一种前体维生素能大量透过皮肤，而是在真皮和表皮中都在皮肤中蓄积。它们比目前使用的醋酸酯更具亲水性且更易溶于水。
