证候类中药新药研发的中医理论基础探讨——基于古代文献的中医方药干预模式研究

《证候类中药新药临床研究技术指导原则》中证候类中药新药的研发在学界仍存在质疑,针对单纯中医证候进行治疗的中药复方制剂是否符合中医理论尚不明确,其较主治为病证结合的中药复方制剂的临床优势尚不清楚。该文从中医传统理论入手,通过溯源历代古籍中的中医干预理念,从干预模式、干预层次、方剂理论3个角度提出三维N阶理论,从而阐明证候类中药新药符合中医传统理论。第一维度,归纳出中医方药的干预模式,可分为围绕疾病、围绕病机、围绕症状这3类,进而提炼出干预的基本元素为:体质、疾病、病因、病机、病位、症状、西医病理、西医指标。其中,针对体质、围绕病机的模式为证候类新药的研发提供了理论可能性,而围绕疾病的干预模式则适合病证结合新药研发。第二维度,汇总历代中医干预的层次,可分为:阴阳、气血津液、脏腑、经络、三焦、卫气营血、六经与局部。其中,针对阴阳、气血津液、经络等较宽泛的层次则适合进行证候类新药研发。第三维度,根据适应症范围方药大致分为4类:适应症较为广泛的方剂、干预脏腑病机的方剂、疾病针对性强的方剂以及症状针对性强的方剂,其中,前两者适合证候类中药新药研发,而疾病针对性强的方剂则适合病证结合新药研发。通过三维N阶理论进一步厘清证候类中药新药的临床定位及较病证结合新药的理论优势:对于新型疾病(疾病基本病机、发生发展规律不清楚)、复杂疾病、合并疾病、老年疾病,以及针对体质的调理,可以考虑证候类新药研发。

Disputes about the research and development of syndrome traditional Chinese medicine(TCM) new drug in Guidance for syndrome TCM new drug development still exist, including the fact that it is unclear whether the compound TCM preparations just targeting a sort of syndrome is in line with the TCM theory and that it is obscure what are clinical advantages of syndrome new drug as compared with new drug targeting both disease and syndrome. Based on TCM classical theory, dating back to intervention opinions of successive dynasties, theory of three-dimensional N levels was proposed from the aspects of intervention modes, intervention latitudes and formulae to illustrate that the syndrome TCM new drug is in line with TCM theory. As for the first dimension, the intervention modes of TCM could be classified into targeting disease, targeting pathology and targeting symptoms, and the basic elements were extracted as constitution, disease, pathogenesis, pathology, location, symptoms, Western medicine pathology and Western medicine indicators. Among them, the mode targeting TCM constitution and the mode targeting pathology provided the theoretical possibility of TCM syndrome new drug, while the mode targeting disease was suitable for disease syndrome new drug. As for the second dimension, the intervention latitudes were summarized, including Yin-Yang, Qi-blood-body fluid, viscera, meridian, tri-jiao, Wei-Qi-Ying-blood, six channels, and local part. The relatively broad latitudes such as Yin-Yang, Qi-blood-body fluid, and meridian might be suitable for the development of TCM syndrome new drug. As for the third dimension, the TCM formulae could be divided into four types according to the range of indications, including broad indications, viscera pathogenesis indications, disease-targeting indications and symptom-targeting indications. The first two types were suitable for TCM syndrome new drug development, while the disease-targeting indication type fit for disease-syndrome new drug. According to theory of three dimensional N levels, the clinical orientation of syndrome TCM new drugs and their advantages over disease-syndrome new drugs were as follows: syndrome TCM new drugs may be considered for novel disease without clear basic pathogenesis or advance regulation, complicated diseases, complicating diseases, geriatric disease and ba-lancing TCM constitution.