Development and evaluation of novel biodegradable transdermal penetration enhancers

新型可生物降解透皮渗透促进剂的开发与评价

基本信息

批准号：
09672281
负责人：
KUBO Kazuyoshi
金额：
$ 1.92万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1998
项目状态：
已结题

项目摘要

This studies were aimed to develop the transdermal therapeutic system of highly ionizable drugs by ion pair formation with novel biodegradable counter ions.The following results were obtained.(1) Novel biodegradable triglycerides having quaternary ammonium group (YKS) were synthesized as counter ions for ion pair complexation with salicylate or cromoglicate (SCG) (model anionic drugs).The permeability of these anionic drugs through the rat skin was significantly increased by lipophilic ion pair formation in the presence of the YKS.(2) The biodegradability of YKS were illustrated by the pH-stability experiments.Judging from the primary irritation indices, YKS-21 had less cutaneous irritancy compared with Azone.(3) The combination of pretreatment with YKS and ion pair formation was more effective for ion pair transport.(4) The maximum flux and permeability coefficient of SCG from SCG-YKS ion pair in propylene glycol/isopropyl alcohol/isopropyl myristate(15 : 75 : 1O)were about 15 and 3 times respectively higher than those of SCG alone in the same vehicle mixture.(5) The plasma concentrations after topical application to the rat were simulated using obtained permeation and disposition parameters.Although there were some differences in the time course patterns, it was found that the percutaneous penetration of SCG was increased by ion pair formation with YKS in vivo as well.The results of this study suggest that it may be possible through the selection of appropriate counter ions to improve the efficiency of transdermal penetration of other highly ionized drugs, and that ion pair formation is an important consideration in the formulation of ionized drugs.

这项研究的目的是通过离子对形成与新型可生物降解的反离子的高度离子药物的透皮治疗系统。（1）获得了具有Quaternary ammhymonium群（YKS）的新型可生物降解甘油三酸酯（YKS）的新型可生物降解的甘油三酸酯，作为与药物（cromogoglate or cromoglate or scgion compection consection composition comportiation contion consection comportiation composition composition composition）。在YK的存在下，通过亲脂离子对的形成，这些阴离子通过大鼠皮肤的渗透性显着增加。（2）通过pH稳定性实验判断YK的生物降解性。与主要的刺激性指标相比，与Azone相比，YKS-21的皮肤降低了。（4）在丙烯乙二醇/异丙醇/异丙基醇/异丙基肉豆蔻酸酯（15：75：1O）中，SCG离子对的最大通量和渗透率系数（15：75：1O）的最大通量和渗透率分别比单独使用的静态浓度及其在同一载体中的SCG分别高15倍和3倍。 were some differences in the time course patterns, it was found that the percutaneous penetration of SCG was increased by ion pair formation with YKS in vivo as well.The results of this study suggest that it may be possible through the selection of appropriate counter ions to improve the efficiency of transdermal penetration of other highly ionized drugs, and that ion pair formation is an important consideration in the formulation of ionized drugs.