基于多指标降维判别分析的中药药对配方颗粒汤剂与传统汤剂差异规律研究

The traditional decoction (TD) is an important weapon of the Chinese medicine treatment, and its many shortcomings such as preparation inconvenience seriously restrict its application. Dispensing Granule of Chinese Medicine(DGCM) considerably improved its most shortcomings, but for a long time it has not arrived at a consensus by the industry,one of the fundamental reason is that the foundational research on the differences between DGCM decoction (DGD) and TD is not enough. Our preliminary research results showed that some of the data characteristic between them is different, but there are certain rules to follow. In this project, the authors intend to select three classic pair-bound Chinese medicine such as Shaoyao Gancao Decoction to conduct a study. By obtaining the multi-index information of LC-MS fingerprints, serum fingerprint and pharmacodynamics, and based on the comparison of six single herbs of pair-bound Chinese medicine, using suitable methods of dimension reduction for multidimensional data, we will carry out the qualitative and quantitative comparison of combination of multi-level, combination of horizontal and vertical integration, combination of subjective and objective (weight), combination of graphical and abstract combination, selection and adjustment of the suitable concentration ratio,while building discriminant function under a certain confidence level to discriminant their differences which is accorded to judge whether it can be equivalent alternative, raising approach when they are non-equivalent. On this basis, validation of compound will be carried out, then sum up differentia regularity between DGD and TD , condense initial potency characteristics, and lay the foundation for the decoction reform and scientific and rational application of DGCM.

传统汤剂（TD）是中医治病的重要武器，而其制备不便等弊端严重制约其应用。中药配方颗粒（DGCM）改进了其诸多弊端，但长期未获业界共识，根本原因之一是DGCM汤剂（DGD）与TD的差异规律等基础研究薄弱。课题组前期研究结果表明，二者之间的若干数据特征的差异性不一，但有一定的规律可循。本课题拟化繁为简，以相须药对研究为切入点，选择芍药甘草汤等3个经典药对，获取LC-MS指纹图谱、血清指纹图谱、药效学多层次指标信息，在全面对比其中6个单味药的基础上，基于适宜的多维数据降维方法，进行多层次结合、横纵向结合、主客观结合（权重）、图形化与抽象化结合的定性定量对比，经适宜的浓缩比等参数的筛选和调整，构建一定置信度下判别其差异性的判别函数，以判别其是否可等效替代，并提出不等效时的处理方法。在此基础上进行复方验证，进而总结二者的共性差异规律，凝练其初步的药性特点，为汤剂改革及DGCM的科学合理应用奠定基础。

中药配方颗粒（DGCM）改进了传统汤剂的诸多弊端，但长期未获业界共识，根本原因之一是DGCM汤剂（DGD）与TD的差异规律等基础研究薄弱。因此，阐明DGCM汤剂与传统汤剂的差异规律是DGCM科学合理应用的必要前提。. 课题组首先以赤芍、黄柏、黄芩、黄连等单味药为切入点，获取了样品的指纹图谱，并利用PCA等方法进行了判别分析。结果传统汤剂与配方颗粒汤剂明显分为两类，且二者之间只有成分含量的差异，不存在成分种类的区别。随后测定了赤芍、黄芩、黄连等单味药的入血成分和药理药效指标，并结合化学成分综合比较了非挥发性单味中药配方颗粒汤剂与传统汤剂的差异，结果非挥发性中药配方颗粒汤剂中75%的指标性成分的含量均显著低于传统汤剂（P＜0.05），而80%的厂家生产的配方颗粒的临床当量均高于传统汤剂实际用量。基于上述现状，项目组建立了科学的、合理的可对配方颗粒当量进行校正的平均倍数法、峰面积加和法，并对赤芍、黄芩等配方颗粒的当量进行了校正。在单味药的基础上，课题组开展了当归补血汤、芍药甘草汤、桂枝甘草汤等药对配方颗粒汤剂与传统汤剂的差异规律研究，获取了上述样品的指纹图谱，并测定了芍药甘草汤等样品的入血成分含量和药理药效指标。实验表明药对传统汤剂中60%的指标性成分的含量均极显著高于配方颗粒汤剂（P＜0.01）。此外，项目组还通过色谱轮廓结合化学计量学方法研究了不同厂家柴胡配方颗粒间的差异，发现该品种配方颗粒的质量仍有待规范。项目还开展了红花、柴胡配方颗粒的定性定量鉴别研究，并建立了专属性的质量控制方法；起草了中药配方颗粒包装规范；开发了一种用于中药配方颗粒质量检测的智能感官融合分析仪器和一种测试数据组中异常值的批量、循环、快速剔除的新方法，为配方颗粒的合理应用奠定了基础。. 阐明配方颗粒汤剂与传统汤剂的差异规律是药学研究者长期面临的课题。在本项目基础上，对建立的一定置信度下的判别函数进行深层次的验证，将进一步为配方颗粒的合理应用奠定基础。