Topical delivery of retinyl ascorbate co-drug - 1. Synthesis, penetration into and permeation across human skin
Topical delivery of retinyl ascorbate co-drug - 1. Synthesis, penetration into and permeation across human skin
复制标题
DOI：
10.1016/j.ijpharm.2004.05.008
复制
发表时间：
2004-08-06
影响因子：
5.8
通讯作者：
Heard, CM
中科院分区：
文献类型：
--
作者：
Abdulmajed, K;Heard, CM
采用一种新的合成方法，以全反式维甲酸氯（RA）和L-抗坏血酸（阿萨）为原料，在乙醇中于低温下合成了抗坏血酸维生素A酯（RA-阿萨）。测定了其log P、在Me：PBS（50/50，pH 4.8）中的溶解度和降解常数。使用热分离的人皮肤膜测定通量和渗透系数，并且使用全厚度人通过胶带剥离测定皮肤渗透。所有实验均与棕榈酸视黄酯（Rol-Rl）和棕榈酸抗坏血酸酯（AsA-Rl）平行进行，其用于商业局部制剂中。RA-阿萨具有良好的log P（2.2），其稳定性远大于RA和阿萨，但与Rol-D和AsA-D相似。RA-AsA的通量低于Rol-Bronze和AsA-Bronze。RA-阿萨也表现出比其他两种酯更高的皮肤保留，但比来自Rol-Roll的视黄醇和来自AsA-Roll的抗坏血酸向活表皮递送更多的RA和阿萨。总之，数据表明RA-AsA联合药物用于治疗由UV诱导的自由基产生引起的皮肤损伤的潜在价值。(C)2004 Elsevier B. V.保留所有权利。
A novel synthetic technique was used to synthesise the co-drug retinyl ascorbate (RA-AsA) ester from all-trans-retinyl chloride (RA) and L-ascorbic acid (AsA) suspended in ethanol at low temperature. Its log P, solubility in a Me:PBS, 50/50 at pH 4.8 and degradation constant were determined. The flux and permeation coefficient were determined using heat separated human skin membrane, and skin penetration was determined by tape stripping using full thickness human. All experiments were performed in parallel with retinyl palmitate (Rol-Pal) and ascorbyl palmitate (AsA-Pal), which are used in commercial topical formulations. RA-AsA exhibited favourable log P (2.2), with stability much greater than RA and AsA, but similar stability to Rol-Pal and AsA-Pal. The flux of RA-AsA was lower than for Rol-Pal and AsA-Pal. RA-AsA also demonstrated higher skin retention than the other two esters, but delivered more RA and AsA to the viable epidermis than retinol from Rol-Pal and ascorbic acid from AsA-Pal. Overall, the data suggest the potential value of RA-AsA co-drug for the purpose of treating damage to skin resulting from UV-induced production of free radicals. (C) 2004 Elsevier B.V. All rights reserved.