中药复方有效成分均匀设计配伍浓度比与药效之间相关性研究

The study of traditional Chinese medicine compound recipe have been not any technical support system which could meet Traditional Chinese medicine theory and also suitable for large-scale study.Based on previous established new technologies of Uniform design-High throughput screening (UD-HTS)，the active ingredient of 11 kinds in Radix Salviae Miltiorrhizae (RXM) and 3 kinds in Sanchi had been studied by UD-HTS. Selected Compound Danshen Tablets (CDT) which has Gong Satsukai prescription Ingenious，reliable efficacy and more research efficacy as targeted drug，were expanded study of UD-HTS. In this project will choose a total of 20 kinds of ingredients, including 13 kinds of RXM, 6 kinds of notoginseng and borneol, which have been reported that have exactly efficacy. By use of UD, Petaflops interactive compatibility of 20 kinds of ingredients and 7 levels of concentrations can be reduced to nearly 100 experiments. Then we'll use efficacy evaluation models with multiple target spot (Series disease model in vivo or in vitro, gene regulation, protein regulation) and HTS technology platform to quick screen and confirm a kind of compatibility better than traditional medicine compatibility. So we can greatly reduce the cost of research. Through regulation and control of the content of the active ingredients of traditional Chinese medicine, according to the pharmacodynamic characteristics of the treatment for different disease models, we try to develop new targeted stronger medicines for different therapeutic purposes. To optimize the UD-HTS technology, to develop a viable industry standard for large-scale study of traditional Chinese medicine, then to apply to all areas on traditional Chinese medicine research, to establish a demonstration base for rapid pharmacodynamic screening of the active ingredients of traditional Chinese medicine group. With all of these, Chinese medicine research and development Will gradually achieved large-scale production.

中药复方尚无兼顾传统中药理论、适合大规模研究的技术支撑体系。本项目基于已建立的均匀设计-高通量筛选(UD-HTS)新技术，在11种丹参有效成分及5种三七皂苷成分的UD-HTS的基础上，选定"君臣佐使"组方精妙、疗效确切、研究较充分的复方丹参片为切入点，进行扩大UD-HTS研究。以君药丹参13种成分、臣药三七6种成分和佐使药冰片，共20种已报道有确切疗效的成分，7个浓度水平，通过UD将千万亿次交互配伍减为近百次实验，通过多靶点(系列疾病体内外模型、基因或蛋白调控)药效评价，依托HTS技术平台快速筛选，确定优于传统中药复方配伍，降低研究成本。通过调控中药复方有效成分配伍，根据治疗不同浓度水平配伍疗效特点，开发出不同治疗目的、针对性更强的创新药。优化UD-HTS技术，制定可行的中药复方大规模研究行业标准推广应用于中医药研究各领域，建立中药复方有效成分群快速药效学筛选示范性基地，逐步进入规模化生产

本项目在前期建立的中药复方大规模均匀设计-高通量筛选(UD-HTS)技术体系的基础上，以蛇床子、丹参等作为研究的切入点。选定有较好活性的多种有效成分，进行多水平均匀设计有效成分群组合，诠释了中药复方有效成分在配伍中的药用价值；并依托HTS 技术平台快速筛选，明确最佳配伍的化学基础，为新药的研发提供理论基础；同时通过药效学研究，探明浓度差异对药效的影响，在获得最佳配伍的同时，获得了最佳配伍浓度。结合中药有效成份的作用机制，用不同动物病理模型进行了药效学研究，深入探讨配伍量的变化对药效影响的机制，为配伍量与药效的关系规律提供理论依据。本研究建立了适用于进行大规模中药及有效成分群配伍药效研究的快速、高效的研究模式。本项目在前期工作的基础上，2013年发表科研论文9篇，申报河北省科技成果2项。