中医药理论指导下的中药研究与开发

杨勇（中国药理学会中药与天然药物药理专业委员会委员，中国药科大学新药安全评价研究中心教授，主要从事药理毒理研究。）

在化学药和生物药进入中国之前，中医药已有几千年的人用经验，并形成了其独特的理论体系，中医药在保障和促进人们健康方面具有不可磨灭的功绩。古人对于中医药的认识和经验的总结，是当今中药研发的宝库和基石，中药的开发应基于中医药理论。【Before chemical and biological drugs entered China,TCM with thousands of years of practical experience had already formed its unique theory system.TCM has indelible achievements in safeguarding and promoting human health.The ancients′understanding and summary of prac⁃tical experience of TCM are the treasure house and cornerstone of the current research and development of TCM.The development of TCM should be based on the TCM theory.】

中医药学是指导临床用药的重要理论基础，是一门经验科学。无论是古方还是临床经验方，都有大量的临床经验，组方中药味的配伍以及配比均是经过临床不断试验和反复调整后才确定下来的，组方均有其合理性，符合中医理论。在立项时，建议优先考虑这些符合中医理论、有大量临床经验的组方，降低开发风险。而根据中医临床经验，在中医理论下指导组成的新处方，是在常年用药经验的基础上总结而来，有一定的理论和临床基础，也有一定的开发价值。但新组方尚未经过长期临床观察，有较大的开发风险。而对于采用化学分离手段分离的化学单体或有效成分，此类药物与化学药物相似，但不及化学药物。化学药物一般在成千上万个结构中进行了筛选和优化，而分离的有效成分很难进行大量筛选，即使在非临床试验中有较好的有效性提示，但由于动物模型以及人类疾病之间有很大差异，靶点分布、结合活性等有很大不同；另外，药物在动物和人体中药代动力学也有所不同，所以，非临床试验中观察到的有效性往往很难在临床试验中再现。因此，此类药物开发风险最高。【As an important basic theory for guiding clinical medica⁃tion,TCM is an empirical science.Any prescrip⁃tion,ancient or modern,has a lot of clinical expe⁃rience.The composition and ratio of prescription medicine are the result of clinical trials and repeated adjustments,which are well-grounded and in accordance with the theory of TCM.At the time of project establishment,it is suggested that priority should be given to these prescriptions that conform to the theory of TCM and have a lot of clinical experience to reduce the risk of devel⁃opment.Some new prescriptions with some theo⁃retical and clinical basis also have some value of development,but run a great risk during develop⁃ment for lack of long-term clinical observation.As for a monomer or active ingredient separated by chemical methods,it is similar to but less than a chemical.Compared to chemicals which could be screened and optimized in tens of thousands structures,the separated active ingredients are very difficult for extensive screening.Because there are significant differences between animal models and human diseases,such as the target distribution,binding activity and pharmacokinetics of drugs,the effectiveness observed in non-clinical trials normally is hard to reproduce in clinical trials,which is why the development of such drugs at the high-risk.】

中药的临床定位应以中医药理论为指导，避免西医化。中药的新药研究应扬长避短，临床定位应选择能够突出中医临床优势或特色的治疗领域，如需要多靶点、多途径治疗的疾病领域，如类风湿性关节炎、功能性消化不良和咳嗽变异性哮喘等。中药的创新和开发应以临床价值为导向，应与临床需求相结合，中药临床价值应多元化，不应仅定为疾病的治疗，可定为于生活质量改善、辅助用药等。临床试验的有效性评价建议采用病证结合的模式开展，结合西医疾病诊断标准和中医辨证论治的优势，按照西医疾病的定义进行诊断可最大程度地保证纳入者的同质性，而中医证候分型，兼顾了纳入病例的个体差异和疾病亚型，有利于重要疗效的选择性分析。但证候分型和定量评价是中医临床的难点，目前尚缺乏证候分型的方法和标准。【The clinical orientation of TCM should be guided by the theory of TCM and ward off"western medicine".The study of new drugs of TCM should foster strengths and circumvent weaknesses and the clinical orientation should select areas of therapy which can highlight the clinical advantages and characteristics of TCM,such as diseases with the need for multiple targets and multiple path⁃ways in treatment,including rheumatoid arthritis,functional dyspepsia,cough variant asthma.The innovation and development of TCM should be oriented to clinical value and combined with clinical needs.The clinical value of TCM should be diver⁃sified,not only for the treatment of diseases,but also for improving the quality of life and assistant drugs.It is suggested that the evaluation of the effectiveness of clinical trials be carried out by the mode of combination of diseases and mani⁃festations and combine diagnostic criteria for Western medicine and the advantages of dialectical treatment of TCM.According to the definition of diseases in western medicine,the homogeneity of the recipients can be guaranteed while TCM syndrome classification takes account of the indi⁃vidual differences and subtypes of the cases,which is conducive to the selective analysis of important therapeutic effects.However,syndrome classification and quantitative evaluation are diffi⁃cult points in the clinical practice of TCM.There is still a lack of methods and standards for syndrome differentiation.】

在生产工艺方面，也应在中医药理论指导下开展研究，制备方法应与古代医籍记载基本一致，改变工艺应与“标准煎液”进行对比研究，并充分考虑药材来源、饮片炮制、制剂生产及使用等各个环节影响质量的因素。【In terms of production craft,research should also be carried out under the guidance of the theory of TCM.The preparation method should be selected in accordance with the ancient records of medical books.The changed craftwork should be studied by comparing with the standard decoction and we should take full account of the factors affecting the quality,such as source of medicinal materials,processing,preparation and use.】

建议改变目前的中药质量控制体系。中医理论指导下的中药往往是多成分、多靶点共同起作用，采用任何一种活性成分均不能客观地反映其整体的疗效，中医“辨证施治”用的是药味而不是某一单一化学成分，这两者之间完全是两回事。如何选择控制的化学组分并控制到多少限度是值得深思的问题。中药的质量标准应与中医的疗效相关，中医理论指导下的中药标准化，是目前的难题之一。目前，日本、美国FDA、欧盟以及WHO均推荐采用煎液的指纹图谱表征产品质量的一致性，中药的指纹图谱可完整地表征中药的整体特性，符合中医整体作用的理论，值得我们借鉴。【It is proposed that the current quality control system of TCM be changed.Under the guidance of the theory of TCM,TCM often works through multiple components and multiple targets,which is why no single active ingredient can objectively reflect its overall efficacy.Treatment based on syndrome differentiation of TCM uses medicine rather than a single chemical component,which are totally two different things.How to choose the chemical components to control and how much to control are problems worth thinking.The quality standard of TCM should be related to the curative effect.The standardization of TCM under the guidance of the theory of TCM is one of the difficult problems to be solved now.At present,Japan,FDA in the US,European Union and WHO all recommend the fingerprint of decoction to represent the consistency of product quality.As fingerprint can fully represent the overall characteristics of TCM and is consistent with the theory of the overall role of TCM,it is worth learning from.】