基于成分群与药效相关性探讨银翘散“香气大出即取服”的科学内涵

Scientific and reasonable decoction is very important to the therapeutic effect of traditional Chinese medicine (TCM). How to judge the terminal of extraction is always a technical puzzle for researchers. Yinqiao San is a very famous prescription of acrid-cold herbs relieving superficies which was created by a famous medical scientist. He made an expatiation about decoction time of Yinqiao San. The note is that taking the medicine when smelling out aroma, do not decoct too much. However, the modern Chinese drugs preparation that produced from Yinqiao San didn’t obey the admonition of the author. It always takes several hours to extract essential oil in the modern process of production, which is much longer than the decocting time the author had suggested. Why should Yinqiao San be taken when the fragrance volatilized fiercely? The purpose of the present project was to investigate the dynamic diversity rules of chemical materials and pharmacological actions in the process of decocting of Yinqiao San deeply by applying many modern technologies such as bioassay and knockout-fishing/spectral efficacy integration and characterization method for establishment of the integrated identification strategy of active chemical constituents in Yinqiao San and establishment of optimal decoction method based on the efficacy weighting. In the meantime, the project discloses the chemical profile and in vivo metabolism profile of Yinqiao San with different decoction methods, and ultimately the decoction method based on the efficacy weighting was constructed for Yinqiao San by summing the values of the product for the efficacy weighting and the corresponding chemical profile. The characteristic aroma components and aroma formation mechanism in Yinqiao San will be analyzed by an electronic nose combined with gas chromatography-mass spectrometry (GC-MS). The extraction endpoint is determined through the application of electronic nose, which elucidating the scientific connotation of “If the aroma smell out, you can take the medication”. Ultimately strong scientific evidence to the preparation design and the development of standard of modern Chinese drugs that produced from Yinqiao San was provided.

提取工艺的科学性对保证中药临床疗效至关重要，提取终点的判断一直是困扰研究者的技术难题。银翘散为辛凉解表的中医经典名方，主治风热感冒，原方作者特别强调其煎煮方法“香气大出即取服，勿过煮……过煮则味厚而入中焦矣”。然而，银翘散类方制剂需长时间煎煮提取，这与其传统煎药经验相悖而受到较多质疑。那么，银翘散“香气大出即取服”的科学内涵何在？本项目拟基于前期工作基础，全成分表征银翘散煎煮过程化学成分动态变化规律，开展多成分整合药代动力学研究，利用多种生物活性检测方法综合评价不同煎煮时间药效强弱，通过桥接体内外化学成分谱及药效，明确其最佳煎煮时间；同时利用成分群缺失-捕获/谱效表征技术建立基于活性贡献指数的银翘散有效成分群识别及质量评价体系，并基于GC-MS和电子鼻探讨其“香气大出”的香气物质和呈香机理，最终阐明其“香气大出即取服”的科学内涵，为银翘散类方制剂提取工艺设计和质量评价标准制定提供科学依据。

提取工艺的科学性对保证中药临床疗效至关重要，提取终点的判断一直是困扰研究者的技术难题。银翘散为辛凉解表的中医经典名方，主治风热感冒，原方作者特别强调其煎煮方法“香气大出即取服，勿过煮……过煮则味厚而入中焦矣”。然而，银翘散类方制剂需长时间煎煮提取，这与其传统煎药经验相悖而受到较多质疑。那么，银翘散“香气大出即取服”的科学内涵何在？本项目全成分表征了银翘散煮散与饮片煎煮过程化学成分动态变化规律，开展了多成分整合药代动力学研究，利用多种生物活性检测方法综合评价了不同煎煮时间药效强弱，通过桥接化学成分谱及药效，明确了其最佳煎煮时间；同时利用谱效表征技术建立了基于银翘散有效成分群识别及质量评价体系，并基于GC-MS探讨了其“香气大出”的香气物质和呈香机理，初步阐明了银翘散“香气大出即取服”的科学内涵，为银翘散类方制剂提取工艺设计和质量评价标准制定提供了科学依据。