甘草酸对鬼臼毒素酊剂经皮渗透的双向调控性及减轻不良反应的初步研究  

Bi-directional Regulation of Glycyrrhizic Acid on Transdermal Permeation of Podophyllotoxin Tincture and Preliminary Investigation on Attenuation of Adverse Effects

作　　者：王雅甜 赵博欣[1] 王胜奇[1] 梁倩莹 李国锋[1] 

机构地区：[1]南方医科大学南方医院药学部,广东广州510515

出　　处：《中国医药工业杂志》2016年第7期891-896,共6页Chinese Journal of Pharmaceuticals

摘　　要：采用Franz扩散池以离体大鼠皮肤为屏障进行体外透皮试验，通过高效液相色谱法测定鬼臼毒素（podophyllotoxin，1）含量，评价甘草酸（glycyrrhizic acid，2）对1酊剂经皮渗透行为的影响，并初步探索2对降低酊剂皮肤炎症作用的影响。制备了含有不同浓度（0．1、1、5、10、20和40mg／ml）2的1酊剂。体外透皮试验表明，2对1的经皮渗透具有双向调控作用。当2浓度在0．1～1mg／ml时对1酊剂的皮肤透过作用具有促进作用；当2浓度在5～40mg／ml时对1酊剂的皮肤透过作用产生抑制作用。1酊剂中2浓度为lmg／ml时，1的透过量及速率显著增高（P〈0．001）。粒径测定结果表明，当2浓度在酊剂中高于10mg／ml时，会形成粒径约为265nm的胶束，可能改变了1酊剂的释药过程从而抑制1经皮渗透。然而，当大鼠皮肤以不同浓度2预处理后再给予1酊剂，1的经皮渗透增强，且呈浓度依赖性。采用HE染色和免疫组化方法观察皮肤组织形态，结果表明2可减少1酊剂作用下皮肤炎症因子的分泌。The skin permeation profile ofpodophyllotoxin （1） from the tincture was evaluated by Franz diffusion cells with excised rat skin as a barrier. The concentration of I was determined by HPLC. The effect of glycyrrhizic acid （2） on the transdermal permeation of 1 and its side effect on skin was preliminary investigated. The 1 tinctures containing different concentrations （0.1, 1, 5, 10, 20 and 40 mg/ml） of 2 were prepared. The results of transdermal test showed that there was a bi-directional regulation of 2 on transdermal permeation of 1. It demonstrated a promotion effect on 1 when the concentration of 2 was in the range of 0. 1-1 mg/ml; while in the range of 5-40 mg/ml, the transdermal permeation amounts of I were inhibited. The permeation amount and permeation rate of 1 from the tincture containing 1 mg/ml of 2 were significantly improved （P〈0.001）. The results of particle size determination showed that the drug loaded micelles formed in the tincture with particle size of about 265 nm, which changed the drug release process and limited permeation of 1. However, when 1 tincture was given on the rat skin with pretreatment of 2, the skin permeability and the permeation rate of I were increased in a concentration-dependent manner. HE staining and immunohistochemical assays were used to observe the morphology of the skin tissue. It indicated that 2 could reduce the secretion of skin inflammation factors caused by 1 tincture.

关 键 词：甘草酸 鬼臼毒素 经皮渗透 双向调节 不良反应 药物合用 

分 类 号：R944.9[医药卫生—药剂学]