“精工細(xì)作”是中藥及健康產(chǎn)品研發(fā)與國(guó)際化的基礎(chǔ)

張永鶴（中國(guó)藥理學(xué)會(huì)常務(wù)理事兼秘書長(zhǎng)，中國(guó)藥理學(xué)會(huì)中藥與天然藥物藥理專業(yè)委員會(huì)常務(wù)委員，北京大學(xué)基礎(chǔ)醫(yī)學(xué)院藥理學(xué)教授，主要從事睡眠障礙及其共病發(fā)病機(jī)制和抗抑郁新藥研發(fā)。）

“中藥現(xiàn)代化”口號(hào)已喊了20余年，“分子機(jī)制”不可謂不細(xì)，可為什么我們的中藥新藥以及健康產(chǎn)品至今未能走出國(guó)門？這確實(shí)是一個(gè)需要冷靜思考的問題！我們的中成藥種類繁多，健康產(chǎn)品功能名目繁雜，幾乎可以“包治”百病，可還是走不出國(guó)門。其中原因有很多，如東、西方對(duì)傳統(tǒng)中醫(yī)藥的認(rèn)識(shí)和理解上的差異等。但歸根到底，還是因?yàn)槲覀儸F(xiàn)有的中藥新藥以及健康產(chǎn)品本身仍使外國(guó)人“看不懂，鬧不清”、以致于不信任所致。例如，我們的中藥及健康產(chǎn)品的說明書就很難“看懂”。在功效方面的描述，尚可“理解”，但對(duì)可能引起的不良反應(yīng)的描述卻令人一頭霧水，常常是“尚不明確”，而注意事項(xiàng)中常見“慎用”一詞。“慎用”該如何用？也缺乏進(jìn)一步的說明?！綯he 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?yàn)槿绱?，也就不可避免地?huì)出現(xiàn)“馬兜鈴酸事件”！事實(shí)上，含有馬兜鈴酸的中藥材，如關(guān)木通、廣防己、細(xì)辛和青木香等是中醫(yī)常用的傳統(tǒng)藥材，這些藥材的毒性實(shí)際上早已為中醫(yī)藥學(xué)家所熟知。因此，這類中藥是經(jīng)過炮制和合理的配伍使用的?？涩F(xiàn)如今，為什么面對(duì)采用流行病學(xué)方法推出的“含馬兜鈴酸的中草藥或成為引發(fā)亞洲人群肝癌或泌尿系統(tǒng)癌癥的高風(fēng)險(xiǎn)因素”的結(jié)論（Lai MNet al，J Natl Cancer Inst，2010，102：179-186），卻“有口難辯”？甚至使中藥出現(xiàn)了信任危機(jī)。實(shí)際上這篇文章并未提供馬兜鈴酸導(dǎo)致肝癌的直接證據(jù)，更無中藥導(dǎo)致肝癌的直接證據(jù)?！綯hat′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.】

中醫(yī)是中華民族的瑰寶，為中華民族的繁衍和發(fā)展做出了巨大貢獻(xiàn)。中藥具有毒性是藥物的本質(zhì)，但其臨床療效不容置疑。我們有幾千年的中藥應(yīng)用歷史，也有豐富的經(jīng)驗(yàn)積累，可為什么我們的辯駁又不能令“外人”信服？原因之一，就是我們拿不出大樣本量的、經(jīng)過系統(tǒng)驗(yàn)證的詳盡的臨床數(shù)據(jù)。如果我們能夠提供合理控制中藥效應(yīng)動(dòng)力學(xué)以及可能產(chǎn)生毒副作用的毒代動(dòng)力學(xué)數(shù)據(jù)，例如是否存在敏感人群？多大劑量的馬兜鈴酸、攝入多長(zhǎng)時(shí)間有可能導(dǎo)致毒副作用？同時(shí)，在應(yīng)用中嚴(yán)格監(jiān)控是可以解決問題、限制其毒性的。正如西藥，雖然大部分都是有毒的，但西藥有比較完整的臨床應(yīng)用數(shù)據(jù)和完善的監(jiān)督體系，使得用藥者能夠有比較明晰的認(rèn)識(shí)。應(yīng)該說，在現(xiàn)代科技條件下，只有正視傳統(tǒng)中醫(yī)藥存在的不足與短板，才是清醒的理性表現(xiàn)；相反，漠視世界性的科學(xué)爭(zhēng)議與現(xiàn)代化標(biāo)準(zhǔn)的挑戰(zhàn)，才是文化不自信的表現(xiàn)?！綯CM 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，產(chǎn)品的質(zhì)量標(biāo)準(zhǔn)監(jiān)測(cè)指標(biāo)的制定也缺乏精確的內(nèi)涵標(biāo)準(zhǔn)。盡管我們引入了所謂的“指紋圖譜”技術(shù)。在這一點(diǎn)上，德國(guó)制定的“銀杏葉產(chǎn)品”質(zhì)量的國(guó)際標(biāo)準(zhǔn)仍是我們的痛點(diǎn)。20世紀(jì)80年代后期，筆者曾問過日本著名的人參研究專家田中治教授，“中國(guó)的人參和韓國(guó)的高麗參有何區(qū)別？為什么外國(guó)人更喜歡韓國(guó)人參”。他回答說，“韓國(guó)人參的外觀大小和皂苷含量都很均勻”。時(shí)間已過去近30年，可我國(guó)的人參在國(guó)際市場(chǎng)上的地位似乎仍無明顯的提升。【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.】

總之，中藥新藥或以中藥為原料制成的健康產(chǎn)品，如果能在藥材質(zhì)量、制備工藝過程、臨床療效或功能及其毒副作用與量效和時(shí)效之間的相關(guān)動(dòng)力學(xué)研究、以及系統(tǒng)完善的臨床用藥跟蹤觀察等方面研究得更“精細(xì)”，中藥和健康產(chǎn)品走出國(guó)門、實(shí)現(xiàn)國(guó)際化將指日可待?！綢n 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.】