基于"组分-药效-靶点"作用网络研究四物汤制备工艺环节评价模式

中药复方制剂具有多成分、多靶点作用特性，其制剂工艺的"成分论"质控体系难以保障工艺优选合理性，使得制剂"控而不效"，一直是中药现代化进程的瓶颈和难点。本课题以临床经典"妇科圣方"四物汤为研究对象，在前期四物汤"谱-效-证"复合模型研究基础上，提出假说"中药复方制剂制备工艺的质量评价可通过"组分-药效-靶点"作用网络进行表征，以体现药物和机体应答的多层次性"。课题采用化学指纹技术对四物汤传统汤剂灌胃大鼠入血前后化学组分进行研究，筛选四物汤潜在活性组分群；应用代谢指纹足迹技术对血虚证和原发性痛经动物模型给药前后进行代谢组行为研究，筛选药效靶点，并推测其内源性作用通路；采用神经网络、博弈模型进行多因素交互分析，构建"组分-药效-靶点"作用网络；最后利用构建的评价网络优化四物汤制备工艺环节技术参数，实现制剂过程"组分"动态变化和"药效"质量保证的在线评价，为中药制剂制备工艺环节评价提供新思路。

It's not easy to select rational preparation by using single or just a few compounds as assessment index during the TCM preparation, which is easy to get the preparation "under controlled but ineffective" and has become a bottle-neck of TCM Modernizations. On the base of the combinational research model-"spectrogram-efficacy-case", this subject chooses classical gynecological formula-"Si Wu Tang" as object, putting forward the hypothesis that is the quality evaluation of Chinese Pattern Medicine can be characterization by the functional network, "composition-efficacy-target", to display logical levels of TCM medicine and mechanism.The process of this subject has been made as follows: At first, using chemical fingerprint to study composition of rat blood before and after the intragastric administration and to select potential composition; using metabolic fingerprint to study metabolites of animal models, of blood deficiency and original dysmenorrheal, before and after the medicine and to select effective target and speculate its original functional pathway; the second, using neural network and Game Model to analyze relationships of factors and to build functional network that is "composition-efficacy-target"; At last, making use of functional network to optimize "Si Wu Tang" preparation and build the on-ling evaluation system combined of dynamic composition and efficacy assurance.