三种达玛烷型皂苷的生物药剂学分类及吸收机制研究 |
投稿时间:2018-03-22 点此下载全文
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引用本文:苏元元,付宇,李楠楠,高尧春,刘海波,董政起.三种达玛烷型皂苷的生物药剂学分类及吸收机制研究[J].中国现代中药,2018,20(9):1150-1156 |
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基金项目:“重大新药创制”国家科技重大专项(2015ZX09501005);中国医学科学院医学与健康科技创新工程项目(2016-I2M-1-012) |
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中文摘要:目的:探究人参皂苷Rb1、人参皂苷Rg1、三七皂苷R1的生物药剂学分类(BCS)及吸收机制。方法:首先运用StarDrop软件预测三种皂苷的溶解特性及其吸收是否受P-糖蛋白(P-gp)调控,进一步通过实验测定三种皂苷的溶解度,并以Caco-2细胞单层为模型进行双向转运实验,通过研究时间、给药浓度、P-gp抑制剂对模型药物转运的影响,确定其BCS分类及初步吸收机制。结果:人参皂苷Rb1、Rg1为高溶解性药物,三七皂苷R1为低溶解性药物。StarDrop模型预测溶解性与P-gp结果和实际结果存在一定差异。三种药物的表观渗透系数(Papp)均小于14.96×10-6 cm·s-1,为低渗透性药物,在Caco-2细胞单层的转运呈时间和浓度依赖性,Papp(BL-AP)/(AP-BL)均小于1.5。维拉帕米能降低人参皂苷Rg1和三七皂苷R1的转运速率,对人参皂苷Rb1无影响。结论:人参皂苷Rb1和Rg1为BCSⅢ类药物,三七皂苷R1为BCSⅣ类药物。三种药物均以被动转运为主,且转运不受P-gp调控,同时维拉帕米对人参皂苷Rg1和三七皂苷R1的转运有抑制作用。 |
中文关键词:人参皂苷Rb1 人参皂苷Rg1 三七皂苷R1 生物药剂学分类 Caco-2细胞单层模型 表观渗透系数 StarDrop |
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Biopharmaceutics Classification and Absorption Mechanism of Three Kinds of Dammarane Saponins |
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Abstract:Objective:To study the BCS classification and absorption mechanism of ginsenoside Rb1,ginsenoside Rg1 and notoginsenoside R1.Methods:The StarDrop software was used to predict the solubility of three saponins and whether their absorption was regulated by P-gp.The solubility of three saponins was further determined by experiments.The Caco-2 monolayer membrane was used as a model for the bidirectional transport experiments.By studying the effect of time,concentration and P-gp inhibitor on the transport of the model drugs,the BCS classification and preliminary absorption mechanism of the model drugs were determined.Results:Ginsenoside Rb1,ginsenoside Rg1 were highly soluble drugs,and notoginsenoside R1 was a low solubility drug.The solubility and P-gp results predicted by the StarDrop model were somewhat different from the actual result.The apparent permeability coefficients(Papp)of the three drugs were less than 14.96×10-6 cm·s-1,indicating that they were low permeability drugs.The transport of compounds in Caco-2 was in a time and concentration dependent manner,Papp(BL-AP)/(AP-BL)were less than 1.5.Verapamil could reduce the transport rate of ginsenoside Rg1 and notoginsenoside R1,and has no effect on ginsenoside Rb1.Conclusion:Ginsenoside Rb1 and ginsenoside Rg1 are BCS III drugs,and notoginsenoside R1 is a BCS IV drug.The three drugs are mainly passively transported,and the transport is not regulated by P-gp,and Verapamil inhibited the transport of ginsenoside Rg1 and notoginsenoside R1. |
keywords:Ginsenoside Rb1 ginsenoside Rg1 notoginsenoside R1 biopharmaceutics classification Caco-2 cell monolayer model apparent permeability coefficients StarDrop |
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