【摘要】 目的　评价皮肤角质层和真皮层对药物经皮渗透的影响。方法　选择 5 氟尿嘧啶 ,茶碱 ,氢醌 ,巴比妥 ,硝酸异山梨酯和酮基布洛芬共 6种具不同脂溶性的药物 ,以贴片为试验药剂 ,采用改进Franz扩散池法 ,考察药物经完整皮肤和剥离角质层皮肤的体外透皮能力。结果　药物的脂溶性LogPc和药物经完整或角质层剥离皮肤的透皮能力 (Kp ,cm·h-1)间均具有抛物线关系。然而 ,角质层剥离后 ,药物Kp增加率主要同药物在水中的溶解度有关。渗透促进剂肉豆蔻酸异丙酯 (IPM )加入到贴片中后 ,药物的脂溶性LogPc和其Kp间无抛物线关系。药物经完整皮肤渗透时 ,因加入IPM而引起的Kp增加率随药物LogPc的变小而增加。药物经角质层剥离皮肤渗透时 ,因加入IPM而引起的Kp增加率随药物在IPM中的溶解度增大而增加。结论　本实验为皮肤病态条件 ,如皮肤受伤或溃疡等时药物经皮渗透规律研究提供一种新的方法更多还原

【Abstract】 OBJECTIVE The purpose of this study was to evaluate the barrier function of different skin layers on the percutaneous penetration of model drugs.METHODS 6 kinds of drugs (5 fluorouracil, theophylline, hydroquinone, barbital, isosorbide dinitrate and ketoprofen) with a wide span of lipophilicity were chosen and their in vitro permeability via intact skin or stripped skin was investigated in the patch dosage forms.RESULTS There were characteristic parabolic relationship between the Permeability (Kp cm·h -1 ) of the drugs with different lipophilicity and their Log Pc either via intact skin or stripped skin. However, due to stratum corneum stripped, the increased Kp ratio for test drugs was mainly proportional to their solubility in water. When absorption promoter IPM (isopropyl myristate) was co administered with the drugs, the parabolic relationship no longer existed.For the intact skin, the enhanced Kp ratio of 6 drugs resulting from IPM rose up when drug’s Log Pc decreased.On the other hand, in the case of stripped skin, this enhancement ratio of Kp due to addition of IPM was related to drug’s solubility in IPM, which meant that the enhanced Kp ratio had a gradual rising tendency as drug’s solubility in IPM became larger.CONCLUSION These data and methods represented a novel approach to evaluate the effects of skin damage and skin disease on drug percutaneous absorption.更多还原