中药现代化研究面对的难题

张丹参（中国药理学会常务理事，中国药理学会中药与天然药物药理专业委员会常务委员，河北科技大学教授，主要从事神经药理学和中药药理学研究。）

天然产物是发现新药的丰富资源，从天然产物中寻找新药或新的先导化合物，已经成为世界新药研究领域的重要内容。纵观国内外对中药进行的研究，目前主要集中在单味药的研究和方剂的研究。【Natural products are abundant resources for finding new drugs.Searching for new drugs or new lead compounds from natural products has become an important part of new drug research in the world.The research of TCM is mainly focused on the research of single herbs and the research of compounds in domestic and foreign research.】

应用现代医学方法研究中药复方作用，已有相当长的历史，但在中药作用机制研究方面，多数仍停留在药效观察水平。造成这种现象的原因有3个方面，一是成分复杂，目前应用的方法不能对全部（或大部分）成分进行研究和观察；二是中药作用机制复杂，是多靶点作用，要全面观察存在极大困难。虽然有学者提出了有效成分组学的概念，但中药来源及成分含量的复杂性和多变性导致有效成分及药效的不稳定，是制约中药现代化研究和应用的瓶颈；三是中药复方是一个复杂的体系。复方中的每一味药对于其所包含的化学成分来说，都是一个小复方。【The study on the effects of TCM prescriptions in the application studies medical methods has a long history,but in the research of the mechanism of TCM,most studies still stay at the level of pharmacological effect observa⁃tion.There are three reasons for this.The first is that the ingredients are complex.The methods in current use cannot study and observe all(or most)components.Second,the mechanism of TCM is complex and has multi-target action.It is very difficultto observe itcomprehensively.Although some scholars have put forward the conceptofeffective compound groups,the complexity and variability of the source and component of TCM lead to the instability of effec⁃tive components and efficacy,which is the bottle⁃neck to the research and application of modern⁃ization of TCM.Third,TCM prescriptions are a complex system.Each drug in the prescription is a small compound for its chemical composition.】

中药复方的组成，都是以所含生药量计算。由于种种因素干扰，中药复方有效成分的含量不均衡，使中药生药有效成分的含量不同，导致复方的有效成分含量不均衡，这是中药研究可比性和可重复性的一个难题。【The composition of TCM prescrip⁃tions is calculated with the amount of crude medi⁃cine.Due to the interference of various factors,the content of active ingredients in TCM prescrip⁃trons is not balanced,which leads to the different content of active ingredients of crude drugs,resulting in the imbalance of active ingredients in TCM.This is a difficult problem of comparability and repeatability of TCM research.】

中药复方的药理作用是以组成复方的每一味中药的药理作用为基础，而每味中药的作用又与其有效成分群的作用密切相关。因此，目前的粗制品研究，虽然与传统临床用药方式相符，但由于制剂中有多种成分，成分复杂，这种方法对于阐明中药的作用机制尚不够准确；初步分离精制品研究，虽拓展了给药途径、便于观察药理作用，对开发中药的临床制剂具有重要意义，但由于研究所采取的制备方法各不相同，制剂中所含成分差异较大，不易于进行作用比较。【The pharmacological effects of TCM prescriptions are based on the pharmaco⁃logical effects of each herb in the prescriptions,and the effect of each herb is closely related to its active ingredient group.Although consistent with traditional clinical mode of medication,the current research method on crude product is not accurate enough to clarify the mechanism of action of TCM due to its varietal ingredients and complex compositions.Although the research of preliminary separation of purified products has expanded the routes of administration,made it easy to observe the pharmacological effect and is of great significance for the development of clinical preparations of TCM,the big difference in the composition of the preparation makes mutual comparison of functions difficult due to the different preparation methods adopted in institutes.】

中药的药理作用广泛，使得中药复方作用多样化，而同一味中药在不同配方中的效应不同，决定了其在复方中的作用地位不同，故而有君、臣、佐、使药之分，通过“君臣佐使”相辅相成发挥作用。目前，许多中药及其方剂的研究历史都比较悠久，这些传统复方的药理作用也比较明确，如果依托前期国内外对目标复方的研究基础，选择确定适合复方主治的疾病动物模型进行验证和评价，参考复方各组成的单味药及其有效成分的药理作用，合理、适当扩大地选择有效成分作为研究的有效成分群，尽可能接近复方的原生态配伍，就可能确定其有效成分群。在中药复方的药理作用基础上，选择共同作用的靶点，作为目标复方的筛选作用靶点，在高通量筛选模型基础上，优化创新，使之适合目标复方的研究，进一步分析其作用机制，全面评价中药复方的药理作用，有可能实现中药及其复方的大规模现代化研究的期望。【The wide pharmacological effects of TCM result in the diversification of the role of TCM prescriptions,while the effect of different herbs of TCM is different in different prescrip⁃tions,which determine their different roles in the prescription.There are thus"principal,subordi⁃nate,adjuvant,and guide medicines"in a prescription.All of them work in harmony to make the prescription work.At present,many TCM and their prescriptions have a long history ofresearch,the pharmacologicaleffects of these traditional prescriptions are rather unequivocal.If we are based on the previous studies of the target compound at home and abroad,choose suitable disease animal models for compound indications to verify and appraise,refer to the various pharmacological effects of the single herb and their active ingredients,select more active ingredients as the research group,and get as close as possible to its original ecological compatibility of the compound,it is possible to determine the active ingredient group.Based on the pharmacological effects of TCM prescriptions,we choose the target of common actions as the target of screening target compound.Optimization and innovation on the basis of a high-throughput screening model,butter applicability to the study of the target compound,further analysis of its mechanism,and a compre⁃hensive evaluation of the pharmacological effects of TCM prescriptions can it make possible to achieve the expectations of large-scale modern⁃ization research of TCM and its prescriptions.】