Tanaka M, Iwata Y, Kouzuki Y, Taniguchi K, Matsuda H, Arima H, Tsuchiya S
Research Center, Shiseido Ltd, Yokohama, Japan.
J Pharm Pharmacol. 1995 Nov;47(11):897-900. doi: 10.1111/j.2042-7158.1995.tb03267.x.
A potential use of 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CyD) to solubilize methyl paraben and to suppress its percutaneous absorption was examined, and compared with nonionic surfactant HCO-60. HP-beta-CyD significantly increased the solubility of methyl paraben in water, where the apparent 1:1 stability constant of the soluble complex was determined to be 2150 M-1. The in-vitro cutaneous permeability of methyl paraben through an isolated skin of hairless mouse was suppressed by HP-beta-CyD, thus promoting the bioconversion of methyl paraben to the less toxic metabolite, p-hydroxybenzoic acid (p-HBA) in the epidermis. These effects of HP-beta-CyD were greater than those of HCO-60. HP-beta-CyD (2% w/v) reduced the in-vivo percutaneous absorption of methyl paraben by 66% 24 h after the topical application of a solution containing [14C]methyl paraben to hairless mouse skin. Additionally, the percutaneous absorption of [14C]HP-beta-CyD was confirmed to be extremely low. These results suggest that HP-beta-CyD is useful in liquid preparations of methyl paraben for topical application.
研究了2-羟丙基-β-环糊精（HP-β-CyD）增溶对羟基苯甲酸甲酯并抑制其经皮吸收的潜在用途，并与非离子表面活性剂HCO-60进行了比较。HP-β-CyD显著提高了对羟基苯甲酸甲酯在水中的溶解度，测得可溶性复合物的表观1:1稳定常数为2150 M-1。HP-β-CyD抑制了对羟基苯甲酸甲酯通过无毛小鼠离体皮肤的体外皮肤渗透性，从而促进了对羟基苯甲酸甲酯在表皮中向毒性较小的代谢产物对羟基苯甲酸（p-HBA）的生物转化。HP-β-CyD的这些作用大于HCO-60。在对无毛小鼠皮肤局部应用含[14C]对羟基苯甲酸甲酯的溶液24小时后，HP-β-CyD（2% w/v）使对羟基苯甲酸甲酯的体内经皮吸收降低了66%。此外，证实[14C]HP-β-CyD的经皮吸收极低。这些结果表明，HP-β-CyD可用于对羟基苯甲酸甲酯局部应用的液体制剂。
