基于模型的中药研发

Model-Based Chinese Medicine Development

中药研发由于本身的复杂性面临诸多挑战,尤其是药效成分不明确成为研发的瓶颈,需要新的研发模式予以支撑。本文将吸收入血的已知有效成分和血药浓度较高的代表性成分称为"化学标志物",并与疗效相关的"生物标志物"相关联,建立药动学/药效学(PK/PD)模型,定量分析(model-analysis)试验数据,指导临床试验的定量设计(design by simulation),从而阐述中药复方的有效性、安全性和组方合理性。由于PK/PD建模与模拟可以贯穿临床前至临床试验的整个过程,可以提高新药研究效率和科学审评水平,降低成本,缩短上市时间。另外,研发中配合临床动态设计方法和风险导向的临床前与临床循环推进战略,最终形成"基于模型的中药研发"模式。本文根据国内外建模与模拟的应用实践,阐述了本模式的特点、在不同研发阶段的应用价值和适用条件,旨在为我国药监部门制定中药新药研发政策提供参考。由于中药新药本身的复杂性,并不否定中药其他研发模式的合理性。

The development of the new Chinese medicine(NCM) is facing many challenges due to its complexity,especially the lack of clear effective components becomes the bottleneck of development,and needs a new development mode to support it.In this paper,the known active chemical components absorbed into blood and the representative chemical components with high blood concentration are called "chemical markers",and the pharmacokinetics/pharmacodynamics(PK/PD) model is established by associating them with the "biomarkers" related to the efficacy or safety.The model-analysis to trial data are used to guide the design by simulation for following clinical trials so as to explain the effectiveness,safety and reasonableness of the combination for NCM.Because PK/PD modeling and simulation can run through the whole development process from preclinical experiment to clinical trial,it can improve the efficiency of development and the level of scientific regulatory evaluation,reduce the cost and shorten the time to market.In addition,the development combined with the clinical dynamic design method and the risk-based preclinical and clinical circulation promotion strategy,finally will form the mode of Model-Based Chinese Medicine Development.According to the practice of modeling and simulation worldwide,this paper describes the characteristics of this mode,its application value and applicable conditions in different stages of development to provide a reference for China.s drug regulatory department to formulate the policy of new drug development for NCM.Because of the complexity of the new Chinese medicine itself,it does not deny the rationality of other development modes of NCM.