从临床出发,以信号通路为靶标的复方新药研发策略、途径与实践——六论创建新医药学  

Research Strategy and Practice from Clinical Reality, Targeting at Signaling Pathways for the Innovative Compound Drug——The Sixth Discussion on the Proposal of Holistic Systems Medicine

作　　者：罗国安[1] 王义明[1] 范雪梅[1] 谢媛媛[1] Luo Guoan;Wang Yiming;Fan Xuemei;Xie Yuanyuan(Department of Chemistry,Tsinghua University,Beijing 100084,China)

机构地区：[1]清华大学/教育部中医药现代化网上合作研究中心,北京100084

出　　处：《世界科学技术-中医药现代化》2018年第7期1047-1068,共22页Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology

基　　金：国家自然科学基金委重点基金项目(81130066):基于整体观的中药复方现代化基础研究;负责人;罗国安;国家自然科学基金委重点项目(81230079):细胞膜色谱技术用于安全性和有效性评价的基础研究;负责人:王义明

摘　　要：本文对中医药现代化之路朝向何方之问,提出了新药研发重点将从新化学实体(NCE)转向复方新药(innovative compound drug,ICD)的观点。在分析新化学实体研究开发模式的缺陷——从动物模型和从靶点出发的新药研究开发的局限性基础上,指出"病"(西医)和"证"(中医)具有统一的生物学意义和生物物质基础(基因、蛋白质、代谢物等)。本文提出了基于"系统-系统"(人体系统-药物系统)模式的复方药物的定义和特点,给出了从临床出发,以信号通路为靶标的复方新药(包括中药复方、西药复方和中西药复方)研发策略。以中药方剂糖肾方治疗糖尿病肾病(DN)的临床研究为例,阐述了研究途径和实例。最后,再次提出设立中国"新医药学发展计划"的倡议。This paper puts forward the point of view of the direction of modernization of traditional Chinese medicine and it also raised the orientation of new drug research and development (R&D)changing from the new chemical entity (NCE) to the innovative compound drug (ICD).In the analysis of the defects of the conventional routine based on animal model or mono-target model for NCE R&D,a solution is proposed to bridge the "disease"(western medicine)and "syndrome" (traditional Chinese medicine)with their linkages in biological knowledge and biological material base (gene,protein, metabolites,etc.)The definition and character of compound drug impacting on the basis of "system to system"mode (human system-drug system)were put forward in this manuscript.And the research strategy proceeding from clinical practice,targeting at signaling pathways was proposed for the innovative compound drugs (Traditional Chinese compound drugs,compound chemical drugs,or compound drugs containing Chinese medicine and chemical drugs).The research roadmap was explained with a ease study of clinical research on Tangshen formula for the treatment of diabetic nephropathy.Finally,proposal for the establishment of Chinese Development Project of Holistic Systems Medicine (HSM)"was raised once again.

关 键 词：整体系统医学 新化学实体 复方创新药物 临床系统生物学 信号通路 整合化学物质组学的整体系统生物学 网络药理学 整合生物标志物体系 

分 类 号：R2-03[医药卫生—中医学]