“精工细作”是中药及健康产品研发与国际化的基础

张永鹤（中国药理学会常务理事兼秘书长，中国药理学会中药与天然药物药理专业委员会常务委员，北京大学基础医学院药理学教授，主要从事睡眠障碍及其共病发病机制和抗抑郁新药研发。）

“中药现代化”口号已喊了20余年，“分子机制”不可谓不细，可为什么我们的中药新药以及健康产品至今未能走出国门？这确实是一个需要冷静思考的问题！我们的中成药种类繁多，健康产品功能名目繁杂，几乎可以“包治”百病，可还是走不出国门。其中原因有很多，如东、西方对传统中医药的认识和理解上的差异等。但归根到底，还是因为我们现有的中药新药以及健康产品本身仍使外国人“看不懂，闹不清”、以致于不信任所致。例如，我们的中药及健康产品的说明书就很难“看懂”。在功效方面的描述，尚可“理解”，但对可能引起的不良反应的描述却令人一头雾水，常常是“尚不明确”，而注意事项中常见“慎用”一词。“慎用”该如何用？也缺乏进一步的说明。【The slogan to"modernize TCM"has been articulated for more than 20 years,the molecular mechanism of which is far from inexhaustive.But why have our new drugs of TCM and health products failed to go abroad so far?This is really a question that calls for calm thought.They still cannot make their way abroad although there are a large variety of Chinese patent medicines and the functions of health products are complicated,with which almost all diseases can be cured.There are numerous reasons,such as the different understanding and comprehension of TCM between the East and the West.But what counts most is that the new drugs of TCM and health products availabe now are not easily understood by foreigners,leading to their distrust in them.For instance,the instruction books of our TCM and health products are incomprehensible to westerners.The descriptions of their functions can be"understandable".But the descriptions of the adverse effects that might be caused are confusing,because they are often described as"not clear yet"and the words"caution"can be easily found in instructions.How to use"with caution"?There is no more explanation.】

正因为如此，也就不可避免地会出现“马兜铃酸事件”！事实上，含有马兜铃酸的中药材，如关木通、广防己、细辛和青木香等是中医常用的传统药材，这些药材的毒性实际上早已为中医药学家所熟知。因此，这类中药是经过炮制和合理的配伍使用的。可现如今，为什么面对采用流行病学方法推出的“含马兜铃酸的中草药或成为引发亚洲人群肝癌或泌尿系统癌症的高风险因素”的结论（Lai MNet al，J Natl Cancer Inst，2010，102：179-186），却“有口难辩”？甚至使中药出现了信任危机。实际上这篇文章并未提供马兜铃酸导致肝癌的直接证据，更无中药导致肝癌的直接证据。【That′s why the"aristolochic acid event"happened inevitably.In fact,those drugs of TCM which contain aris⁃tolochic acid,such as Caulis Aristolochiae Mans⁃huriensis,Aristolochia fangchi,Asarum sieboldi Mig.and Radix Aristolochiae are traditional medi⁃cines often used by doctors of TCM,whose toxicity has been known very well by TCM scientists for a long time.So the use of this kind of TCM is preceded by preparations and rational compatibility.But nowadays,why is it"difficult to argue"in face of the conclusion(Lai MNet al,J Natl Cancer Inst,2010,102:179-186)which is speculated by epide⁃miological approaches that″Chinese herbal medi⁃cines containing aristolochic acid may become a high-risk factor for liver cancer or urinary system cancer in Asia populations?″It can even lead to the crisis of confidence in TCM.In fact,this article has provided neither the direct evidence of liver cancer caused by aristolochic acid nor by TCM.】

中医是中华民族的瑰宝，为中华民族的繁衍和发展做出了巨大贡献。中药具有毒性是药物的本质，但其临床疗效不容置疑。我们有几千年的中药应用历史，也有丰富的经验积累，可为什么我们的辩驳又不能令“外人”信服？原因之一，就是我们拿不出大样本量的、经过系统验证的详尽的临床数据。如果我们能够提供合理控制中药效应动力学以及可能产生毒副作用的毒代动力学数据，例如是否存在敏感人群？多大剂量的马兜铃酸、摄入多长时间有可能导致毒副作用？同时，在应用中严格监控是可以解决问题、限制其毒性的。正如西药，虽然大部分都是有毒的，但西药有比较完整的临床应用数据和完善的监督体系，使得用药者能够有比较明晰的认识。应该说，在现代科技条件下，只有正视传统中医药存在的不足与短板，才是清醒的理性表现；相反，漠视世界性的科学争议与现代化标准的挑战，才是文化不自信的表现。【TCM is a great trea⁃sure of the Chinese nation and has made great contributions to the reproduction and develop⁃ment of the Chinese nation.The nature of TCM is such that it is toxic.But its clinical efficacy is beyond doubt.TCM has been used for thou⁃sands of years and the experience is abundant.But why do our arguments fail to convince"foreigners"?One of the reasons is that we can⁃not provide large-sized clinical data with system⁃atic and exhaustive verification.If we are able to pro⁃vide toxicokinetics of the rational control of effect dynamics of TCM and the toxic side effects that might be generated,such as the presence or absence of sensitive populations,the right dose of aristolochic acid,how long intake can lead to side effects,and the rigorous surveillance in application,then we can help address these issues and control the toxicities.In western medicine,most of the drugs are toxic,but they have rela⁃tively complete clinical application data and an impeccable supervision system,making possible a clearer understanding of them to consumers.It should be said that under the condition of modern technologies,only when the shortcomings and disadvantages of TCM are confronted can there be a sober rational expression.On the contrary,disregarding the challenges of worldwide scientific controversies and the standards of moderniza⁃tion is not a manifestation of cultural confidence.】

另外，产品的质量标准监测指标的制定也缺乏精确的内涵标准。尽管我们引入了所谓的“指纹图谱”技术。在这一点上，德国制定的“银杏叶产品”质量的国际标准仍是我们的痛点。20世纪80年代后期，笔者曾问过日本著名的人参研究专家田中治教授，“中国的人参和韩国的高丽参有何区别？为什么外国人更喜欢韩国人参”。他回答说，“韩国人参的外观大小和皂苷含量都很均匀”。时间已过去近30年，可我国的人参在国际市场上的地位似乎仍无明显的提升。【In addition,the establishment of surveillance indicators of the quality standards of products lacks accurate definition of content stan⁃dards.Despite the so-called"fingerprinting"tech⁃nology we introduced,the international stan⁃dards of the quality of"Ginkgo bilobaproducts"established by Germans are still a pity for us at this point.In the late 1980s,I once asked Professor Osamu Tanaka,a well-known Japanese ginseng researcher,"What is the difference between Chinese ginseng and Korean ginseng?Why do foreigners prefer Korean ginseng?"He replied,"the size and saponin content of Korean ginseng are very uniform".Nearly 30 years have passed,but the international status of Chinese ginseng has been witnessed any significant improve⁃ment.】

总之，中药新药或以中药为原料制成的健康产品，如果能在药材质量、制备工艺过程、临床疗效或功能及其毒副作用与量效和时效之间的相关动力学研究、以及系统完善的临床用药跟踪观察等方面研究得更“精细”，中药和健康产品走出国门、实现国际化将指日可待。【In short,it will not be long before TCM and health products are accepted abroadandbecomeinternationalizedifnew drugs of TCM or health products made from TCM can improve the quality,preparation processes,the relevant dynamics research between the clinical efficacy or function and their toxic side effects and dose-effect and time-related effects,and the systematic and well-established methods for tracking and observation of clinical medication and other aspects.】