中药安全性评价理论创新与技术突破:病证毒理学

Theoretical innovation and technological breakthroughs in the safety evaluation of traditional Chinese medicine:disease-syndrome-based toxicology

目的提出病证毒理学理论及方法体系,皆在促进病证毒理学在中药新药开发、中药临床安全性评价以及中药安全精准用药对策制定方面的科学、合理和高效运用,促进中医药事业健康可持续发展。方法结合病证毒理学实践运用情况,全面定义病证毒理学的外延和内涵,并系统梳理基于病证毒理学的中药安全性研究新理论、新方法和新发现。结果中药毒性主要分为固有毒性和特异质毒性2种类型,由于特异质毒性具有偶发性,易感性和难预测等特点,常规毒理学模式和方法难以评价,为此本团队传承创新中医“有故无殒”毒效思想,2016年首次提出病证毒理学理论和方法,皆在突破常规毒理学模式和方法局限性,科学厘清遗传、体质、疾病和证候等机体因素对中药安全性的影响规律和主次关系,解决中药特异质毒性评价难题。近年来,本团队在不断完善和优化病证毒理学理论和方法体系基础上,以临床真实世界和体内外病证易感模型为主要评价模式,开展了何首乌、补骨脂和淫羊藿等中药及及其相关制剂特异质毒性的易感人发现识别、成因机制解析及风险防控对策研究,破解了系列传统“无毒”中药安全性评价及风险防控难题。结论病证毒理学不仅可以用于特异质毒性中药的易感人群识别、成因机制解析以及风险防控对策研究,还可以用于固有毒性中药的“病(证)-量-时-毒-效”关系以及安全治疗窗研究。病证毒理学创新发展了中药毒理学理论和方法,为中药安全精准用药提供了奠基性理论和技术支撑。

Objective To promote the scientific,rational and efficient application of disease-syndrome-based toxicology in the development of new traditional Chinese medicine drugs,the clinical safety evaluation of traditional Chinese medicine(TCM),and the formulation of safe and precise medicine countermeasures,and promote the healthy and sustainable development of TCM.Methods In combination with the application of disease-syndrome-based toxicology in practice,its extension and intension were comprehensively defined.Meanwhile,the new theories,methods and discoveries of TCM safety research based on disease-syndrome-based toxicology were systematically reviewed.Results The toxicity of TCM is mainly divided into two types:intrinsic toxicity and idiosyncratic toxicity.Due to the sporadicity,susceptibility and unpredictability of idiosyncratic toxicity,conventional toxicological models and methods are difficult to evaluate the idiosyncratic toxicity of TCM.Therefore,the author's team inherited and innovated the idea of"You Gu Wu Yun"in TCM theory,and proposed the theory and method of disease-syndrome-based toxicology for the first time in 2016,aiming to break through the limitations of conventional toxicological models and methods,scientifically clarify the influence of factors such as heredity,constitution,disease syndrome,and other factors on the safety of TCM,and solve the problem of evaluating the idiosyncratic toxicity of TCM.In recent years,based on the continuous improvement and optimization of the disease-syndrome-based toxicology theory and methodological system,the author's team used the clinical real-world and the in vivo and in vitro susceptibility model of disease and syndrome as the main evaluation model,and carried out the research on the identification of susceptible population,genetic mechanism analysis and risk prevention and control countermeasures of the idiosyncratic toxicity of TCM such as Polygonum multiflorum,Fructus Psoraleae and Herba Epimedii,which solved the problems of safety evaluation and risk prevention and control of a series of traditional“non-toxic”TCM.Conclusion Disease-syndrome-based toxicology can not only be used for the identification of susceptible populations,mechanism analysis,and risk prevention and control strategies of TCM with idiosyncratic toxicity,but also for the study of the“disease(syndrome)-dose-timetoxicity-effect”relationship and safe therapeutic window of TCM with intrinsic toxicity.