基于“相态-吸收-药效”阐释三黄泻心汤“混相体”制剂特征与功效相关性的基础研究

Sanhuang Xiexin Decoction first recorded in "Golden Chamber Synopsis", is a classic prescription used for hematemesis or epistaxis, which are caused by exuberant fire in TCM. Previously, applicant found that there were amount of floccules in the Sanhuang Xiexin Decoction, which including true solution, colloidal solution and suspension called "miscible phase" was an important carrier of the pharmacodynamics substances of the decoction. The ancients emphasized to take at a draught, after that floccules released slowly and worked effectively in the gastrointestinal tract. Therefore, a hypothesis was proposed herein that pharmacodynamics substances in the Sanhuang Xiexin Decoction have changed the physical and chemical characters complexly, with free, combinative and complex states in the decoction could be slowly and sustained, absorbed in gastrointestinal tract due to the "miscible phase" feature of the decoction. The subject was based on the comparison of the separated decoction and the combined decoction, and the phase state of the Decoction will be primarily characterized by technique of molecular simulation docking and means of interface chemistry. Besides, the Caco-2 cell model was combined with the in situ intestinal perfusion model would be applied for the study of the absorption characteristics of the components. At last, the efficacy of the drug would be evaluated by disease and syndrome animal model of TCM. In this way, "microscopic phase" and "macroscopic effect" is connected in series with "gastrointestinal absorption". The model of "phase state-gastrointestinal absorption-drug effect" will be established, and the potential links between "phase state" and "drug effect" will be found. Scientific interpretation the relativity between the characteristics and the efficacy of the "miscible phase" preparation Sanhuang Xiexin Decoction was explored and novel research methodology on "combined decocting" for the decoction of TCM was provided.

三黄泻心汤首载于《金匮要略》，为治疗火热壅盛、吐衄之经方，申请者前期研究发现三黄泻心汤复方合煎后产生大量絮状物，汤液呈真溶液、胶体溶液、混悬液的不同形态的“混相体”，为汤液药效物质的重要载体。古人强调顿服，顿服后絮状物在胃肠缓慢释放而显效，故提出假说：三黄泻心汤复方合煎时有效成分发生复杂理化变化，药效成分存在游离态、结合态、络合态等多种形式，汤液为“混相体”，通过胃肠消化吸收，药效物质缓慢释放而显效。课题以三黄泻心汤合煎液与分煎液互为对照，应用分子模拟对接技术与理化参数测定相结合，表征汤液相态；通过Caco-2细胞模型与原位肠灌注模型相结合，研究组分吸收特点；采用病证动物模型评价药效表达。以三黄泻心汤组分“吸收”关联 “微观相态”与“宏观药效”，建立“相态-吸收-药效”研究模式，科学阐释三黄泻心汤“混相体”制剂特征与功效的相关性，为中药汤剂“复方合煎”研究提供新思路。

三黄泻心汤首载于《金匮要略》，为治疗火热壅盛、吐衄之经方，前期研究发现三黄泻心汤复方合煎后产生大量絮状物，汤液呈真溶液、胶体溶液、混悬液的不同形态的“混相体”，为汤液药效物质的重要载体。古人强调顿服，顿服后絮状物在胃肠缓慢释放而显效，故三黄泻心汤复方合煎时有效成分发生复杂理化变化，药效成分存在游离态、结合态、络合态等多种形式，汤液为“混相体”，通过胃肠消化吸收，药效物质缓慢释放而显效。课题以三黄泻心汤合煎液与分煎液互为对照，应用多指标成分动态变化和分布规律，表征汤液相态间差异；三黄泻心汤各相态样品化学成分及入血成分分析研究组分吸收特点；采用溃疡性结肠炎模型评价药效表达。以三黄泻心汤组分“吸收”关联 “微观相态”与“宏观药效”，建立“相态-吸收-药效”研究模式，科学阐释三黄泻心汤“混相体”制剂特征与功效的相关性，为中药汤剂“复方合煎”研究提供新思路。