制何首乌中主要药效/毒效成分的生物药剂学分类系统评价研究  

A systematic evaluation of biopharmaceutics classification system of main efficacy and toxic ingredients in Polygoni Multiflori Radix Praeparata

作　　者：曹雪晓 任晓亮[1] 王萌[2] 孙立丽[1] 邓雁如[1] CAO Xue-xiao;REN Xiao-liang;WANG Meng;SUN Li-li;DENG Yan-ru(School of Chinese Materia Medica,Tianjin University of Traditional Chinese Medicine,Tianjin 301617,China;Tianjin State Key Laboratory of Modern Chinese Medicine,Tianjin University of Traditional Chinese Medicine,Tianjin 301617,China)

机构地区：[1]天津中医药大学中药学院,天津301617 [2]天津中医药大学中医药研究院,天津301617

出　　处：《中草药》2020年第13期3451-3456,共6页Chinese Traditional and Herbal Drugs

基　　金：国家自然科学基金面上项目“基于对偶传播人工神经网络整合生物药剂学的‘丸者缓也’中药制剂理论分子机制研究”(81873191)。

摘　　要：目的对制何首乌5种主要药效/毒效成分没食子酸、大黄素、二苯乙烯苷、大黄素甲醚和大黄素-8-O-β-D-葡萄糖苷进行生物药剂学分类系统(BCS)研究。方法分别采用平衡溶解度法和外翻肠囊法研究各代表成分的溶解度和渗透性,采用2种软件Pipeline Pilot 7.5和ChemDraw 7.0预测各成分的溶解性和渗透性参数,采用美国食品药物管理局(FDA)标准分别对代表成分实测值与预测值进行经典BCS分类研究,同时评估其相关性。结果初步判定制何首乌中大黄素、大黄素-8-O-β-D-葡萄糖苷及大黄素甲醚为BCSIV类药物;二苯乙烯苷和没食子酸属于BCSⅢ类成分,渗透性是其吸收过程中主要限制因素。蒽醌类化合物的BCS分类研究存在差异,软件预测存在假阳性。结论采用体外生物利用度快速评价方法对制何首乌中5种主要药效/毒效成分进行BCS分类研究,为中药体内吸收预测和体外安全性评价提供研究思路和实验范例。Objective Biopharmaceutics classification system(BCS) of five main pharmacological/toxic components(gallic acid, emodin, stilbene glycoside, physcion, and emodin-8-O-β-D-glucoside) of Polygoni Multiflori Radix Praeparata(PMRP) were carried out. Methods The solubility and permeability of each representative component were studied by equilibrium solubility method and everted intestinal sac method, respectively. Using two softwares(Pipeline Pilot 7.5, ChemDraw 7.0) to predict the solubility and permeability parameters of each component. Classical BCS classification of measured and predicted values of representative components was conducted according to Food and Drug Administration(FDA) standards, and their correlation was evaluated. Results The emodin, emodin-8-O-β-D-glucoside, and physcion in PMRP was preliminary determined as BCS IV drugs. THSG and gallic acid belong to BCS Ⅲ drugs, and permeability was the main limiting factor in their absorption process. There was software which predicts false positives of anthraquinone in BCS classification studies. Conclusion In this study, five main pharmacodynamic/toxic components of PMRP were classified by BCS method, which provided data support and technical reference for in vivo absorption prediction and in vitro safety evaluation of traditional Chinese medicine.

关 键 词：制何首乌 溶解度 渗透性 生物药剂学分类系统 药效 毒效 没食子酸 大黄素 二苯乙烯苷 大黄素甲醚 大黄素-8-O-β-D-葡萄糖苷 平衡溶解度法 外翻肠囊法 相关性 蒽醌 假阳性 体外生物利用度 体内吸收 安全性 

分 类 号：R286.02[医药卫生—中药学]