微透析技术进行复方中药脑局部PK-PD模型的研究

项目名称： 微透析技术进行复方中药脑局部PK-PD模型的研究

项目编号： No.30873443

项目类型： 面上项目

立项/批准年度： 2009

项目学科： 金属学与金属工艺

项目作者： 王利胜

作者单位： 广州中医药大学

项目金额： 30万元

中文摘要： 本课题选取临床疗效确切的芎冰复方制成的芎冰微乳为试验药物，以改良线栓法制备的脑缺血再灌注大鼠模型为用药对象，运用活体、实时的微透析采样技术，同步测定了血浆、脑组织中有效组分川芎嗪、阿魏酸等浓度和脑组织痕量氨基酸类神经递质IAA、EAA等药效指标，分别进行芎冰微乳口服、静脉及鼻黏膜不同给药途径的全身和脑局部药物动力学，以及药效动力学研究，并对药物浓度-时间-药效间的定量关系进行拟合，最终建立了不同给药途径的脑局部PK-PD模型。研究发现在药物作用部位药效和药物浓度之间存在一定的联系，芎冰微乳不同给药方式的脑靶向性也存在差异性，经鼻粘膜给药具有一定的脑内递药特性。本项目的研究成功建立了微透析技术进行中药单体及复方制剂局部药动学研究和动物清醒状态下脑内和静脉同步采样进行脑局部PK-PD模型两个重要的中药复方制剂体内评价的研究平台，为进一步科学评价中药脑靶向给药系统，合理设计给药方案和途径，探索解决中医治疗脑中风疗效不稳定的难题，提供更有力的依据和评价方法。

中文关键词： 复方中药；微透析；芎冰微乳；脑缺血动物模型；脑局部PK-PD模型

英文摘要： This subject chose Xiongbing microemulsion derived from Xiongbing Fufang which had a definite clinical effect as the testing drug and the ischemia reperfusion model in rats established by the modified suture-occluded method as treatment objects, using vivid and real time Intracerebral Microdislysis, and determining the concentrations of effective components such as tetramethylpyrazine and ferulic acid in plasma and brain as well as the pharmacodynamic indexes of the trace Amino Acid Neurotransmitters IAA and EAA in brain, studying the pharmacokinetic and pharmacodynamics of Xiongbing micro emulsion in whole body and brain by different administration ways including oral medication, intravenous and intranasal administration, establishing a quantitative relationship of the concentration-time-effect, finally constructing the PK-PD model in the local cerebra. It is shown that there is certain relationship exist between efficacy in its action site and the concentration of the drug, and there is difference exist among the different administration approaches which reveals intranasal administration has the property of drug delivery. This research had successfully conducted two important research platforms about the in vivo evaluation of the compound preparation，which include the microdialysis technique used to study the local pharmacokinetic of the monomer of Chinese medicine and compound preparation, and the PK-PD model in brain through cerebra and vein sampling synchronously in conscious state of animals, providing more reasonable basis and methods to further evaluate the brain targeting drug delivery system of Chinese medicine scientifically, to design the delivery schemes and ways logically and to explore a way to solve the instability of TCM in curing strokes.

英文关键词： Compound Chinese Medicine；Microdislysis; Xiongbing microemulsion; Ischemia reperfusion model in rats;PK-PD model in brain