摘要
电致孔技术是促进药物经皮吸收的有效方法,已引起国内外透皮给药领域的高度关注。本文以祛风湿药秦艽的水溶性多成分为模型,研究其在电致孔作用下的透皮规律。
本文采用体外和体内经皮渗透试验方法,考察了电致孔电学参数对秦艽多成分透皮的影响,比较了电致孔作用下体外和体内经皮渗透试验的异同,探索了电致孔的促透机理及其安全性,得出以下结论:
(1)首次将中药指纹图谱相似度作为描述秦艽多成分透皮规律的评价方法。对不同参数下接收液中龙胆苦苷含量和相似度双指标进行相关性分析,得到相关系数平均值为0.957,表明相关性非常显著,说明二者的变化规律基本一致,因此可以用龙胆苦苷单一成分随电学参数变化的规律来描述秦艽药液多成分的透皮规律。
(2)对电致孔作用下体外与体内经皮渗透试验进行比较,发现二者最优电学参数条件基本一致,可以利用体外试验研究药物的透皮规律;同时发现药物透过量差异较大,因此为保证临床用药的安全有效,经皮给药系统的开发过程需要进行体内研究。
(3)电致孔促透机理的研究发现,在瞬间电场作用下皮肤角质层由致密结构变成疏松结构,从而降低角质层对药物透皮的阻碍作用;圆形电极产生的脉冲电场促透效果最佳;水溶性促渗剂与电致孔之间具有显著的协同作用。
(4)影响电致孔给药安全性的参数主要有脉冲电压和脉冲频率,其产生不良反应的阈值分别为:脉冲电压300 V,脉冲频率120 pulses/min。
本文研究可知,电致孔透皮给药技术能够增加中药多成分的透过量。在给药安全范围内,将电致孔给药技术应用于中药透皮领域,可以发挥中医药“内病外治”的特色,具有巨大的发展潜力与应用前景。
Electroporation technology is an effective transdermal drug delivery mean which has aroused great concern in the field of transdermal drug delivery system both at home and abroad.In this paper,water-soluble components of gentiana were used as a model to study its role in the electroporation transdermal under the law.
Based on permeation experiments in vitro and in vivo,the influence of electrical parameters of electroporation on transdermal impact on multi-components of gentiana,the difference of in vitro and in vivo permeation experiments was investigated.We also studied the protective mechanism and safty of electroporation.We draw the conclusions as follows:
(1) Fingerprint technique was firstly used for evaluating the rules of electroporation on the transdermal transport of gentiana.As two indicators,the receiving fluid gentiopicroside content and similarity were analyzed.The correlation coefficient is 0.957,which shows that the two are basically the same as the law changes.So we can use the changes of single component gentiopicroside under different electrical parameters to describe the transdermal laws of multi-components within gentiana.
(2)We compared the effect of electroporation in vitro and in vivo percutaneous penetration and found that the optimal electrical parameters of the two conditions are basically the same.So we can explore the laws of transdermal through in vitro experiments. At the same time,the amount of drugs that through skin is significantly different.Penetration tests in vivo should be carried out to reduce the risk.
(3) We found that the dense structure of the stratum corneum become loose structure, which can reduces the cuticle on the role of drug penetration barriers.Experimental results show that the best electrical pulse is generated by circular electrode.And for the first time we found that penetration agent of water-soluble can enhance the force of electroporation.
(4) The main facters arc pulse voltage and pulse frequency,which have a threshold of adverse reactions arc as follows:pulse voltage 300 V,pulse frequency 120 pulses/min.
This paper demonstrated that electroporation technique can increase the amunt of traditional Chinese medicine absorption.Electroporation technology can be widely used as long as it is good for others.
引文
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