中醫(yī)藥理論指導(dǎo)下的中藥研究與開發(fā)

楊勇（中國藥理學(xué)會(huì)中藥與天然藥物藥理專業(yè)委員會(huì)委員，中國藥科大學(xué)新藥安全評(píng)價(jià)研究中心教授，主要從事藥理毒理研究。）

在化學(xué)藥和生物藥進(jìn)入中國之前，中醫(yī)藥已有幾千年的人用經(jīng)驗(yàn)，并形成了其獨(dú)特的理論體系，中醫(yī)藥在保障和促進(jìn)人們健康方面具有不可磨滅的功績。古人對(duì)于中醫(yī)藥的認(rèn)識(shí)和經(jīng)驗(yàn)的總結(jié)，是當(dāng)今中藥研發(fā)的寶庫和基石，中藥的開發(fā)應(yīng)基于中醫(yī)藥理論?！綛efore chemical and biological drugs entered China,TCM with thousands of years of practical experience had already formed its unique theory system.TCM has indelible achievements in safeguarding and promoting human health.The ancients′understanding and summary of prac?tical experience of TCM are the treasure house and cornerstone of the current research and development of TCM.The development of TCM should be based on the TCM theory.】

中醫(yī)藥學(xué)是指導(dǎo)臨床用藥的重要理論基礎(chǔ)，是一門經(jīng)驗(yàn)科學(xué)。無論是古方還是臨床經(jīng)驗(yàn)方，都有大量的臨床經(jīng)驗(yàn)，組方中藥味的配伍以及配比均是經(jīng)過臨床不斷試驗(yàn)和反復(fù)調(diào)整后才確定下來的，組方均有其合理性，符合中醫(yī)理論。在立項(xiàng)時(shí)，建議優(yōu)先考慮這些符合中醫(yī)理論、有大量臨床經(jīng)驗(yàn)的組方，降低開發(fā)風(fēng)險(xiǎn)。而根據(jù)中醫(yī)臨床經(jīng)驗(yàn)，在中醫(yī)理論下指導(dǎo)組成的新處方，是在常年用藥經(jīng)驗(yàn)的基礎(chǔ)上總結(jié)而來，有一定的理論和臨床基礎(chǔ)，也有一定的開發(fā)價(jià)值。但新組方尚未經(jīng)過長期臨床觀察，有較大的開發(fā)風(fēng)險(xiǎn)。而對(duì)于采用化學(xué)分離手段分離的化學(xué)單體或有效成分，此類藥物與化學(xué)藥物相似，但不及化學(xué)藥物?；瘜W(xué)藥物一般在成千上萬個(gè)結(jié)構(gòu)中進(jìn)行了篩選和優(yōu)化，而分離的有效成分很難進(jìn)行大量篩選，即使在非臨床試驗(yàn)中有較好的有效性提示，但由于動(dòng)物模型以及人類疾病之間有很大差異，靶點(diǎn)分布、結(jié)合活性等有很大不同；另外，藥物在動(dòng)物和人體中藥代動(dòng)力學(xué)也有所不同，所以，非臨床試驗(yàn)中觀察到的有效性往往很難在臨床試驗(yàn)中再現(xiàn)。因此，此類藥物開發(fā)風(fēng)險(xiǎn)最高?！続s an important basic theory for guiding clinical medica?tion,TCM is an empirical science.Any prescrip?tion,ancient or modern,has a lot of clinical expe?rience.The composition and ratio of prescription medicine are the result of clinical trials and repeated adjustments,which are well-grounded and in accordance with the theory of TCM.At the time of project establishment,it is suggested that priority should be given to these prescriptions that conform to the theory of TCM and have a lot of clinical experience to reduce the risk of devel?opment.Some new prescriptions with some theo?retical and clinical basis also have some value of development,but run a great risk during develop?ment for lack of long-term clinical observation.As for a monomer or active ingredient separated by chemical methods,it is similar to but less than a chemical.Compared to chemicals which could be screened and optimized in tens of thousands structures,the separated active ingredients are very difficult for extensive screening.Because there are significant differences between animal models and human diseases,such as the target distribution,binding activity and pharmacokinetics of drugs,the effectiveness observed in non-clinical trials normally is hard to reproduce in clinical trials,which is why the development of such drugs at the high-risk.】

中藥的臨床定位應(yīng)以中醫(yī)藥理論為指導(dǎo)，避免西醫(yī)化。中藥的新藥研究應(yīng)揚(yáng)長避短，臨床定位應(yīng)選擇能夠突出中醫(yī)臨床優(yōu)勢或特色的治療領(lǐng)域，如需要多靶點(diǎn)、多途徑治療的疾病領(lǐng)域，如類風(fēng)濕性關(guān)節(jié)炎、功能性消化不良和咳嗽變異性哮喘等。中藥的創(chuàng)新和開發(fā)應(yīng)以臨床價(jià)值為導(dǎo)向，應(yīng)與臨床需求相結(jié)合，中藥臨床價(jià)值應(yīng)多元化，不應(yīng)僅定為疾病的治療，可定為于生活質(zhì)量改善、輔助用藥等。臨床試驗(yàn)的有效性評(píng)價(jià)建議采用病證結(jié)合的模式開展，結(jié)合西醫(yī)疾病診斷標(biāo)準(zhǔn)和中醫(yī)辨證論治的優(yōu)勢，按照西醫(yī)疾病的定義進(jìn)行診斷可最大程度地保證納入者的同質(zhì)性，而中醫(yī)證候分型，兼顧了納入病例的個(gè)體差異和疾病亞型，有利于重要療效的選擇性分析。但證候分型和定量評(píng)價(jià)是中醫(yī)臨床的難點(diǎn)，目前尚缺乏證候分型的方法和標(biāo)準(zhǔn)?！綯he clinical orientation of TCM should be guided by the theory of TCM and ward off"western medicine".The study of new drugs of TCM should foster strengths and circumvent weaknesses and the clinical orientation should select areas of therapy which can highlight the clinical advantages and characteristics of TCM,such as diseases with the need for multiple targets and multiple path?ways in treatment,including rheumatoid arthritis,functional dyspepsia,cough variant asthma.The innovation and development of TCM should be oriented to clinical value and combined with clinical needs.The clinical value of TCM should be diver?sified,not only for the treatment of diseases,but also for improving the quality of life and assistant drugs.It is suggested that the evaluation of the effectiveness of clinical trials be carried out by the mode of combination of diseases and mani?festations and combine diagnostic criteria for Western medicine and the advantages of dialectical treatment of TCM.According to the definition of diseases in western medicine,the homogeneity of the recipients can be guaranteed while TCM syndrome classification takes account of the indi?vidual differences and subtypes of the cases,which is conducive to the selective analysis of important therapeutic effects.However,syndrome classification and quantitative evaluation are diffi?cult points in the clinical practice of TCM.There is still a lack of methods and standards for syndrome differentiation.】

在生產(chǎn)工藝方面，也應(yīng)在中醫(yī)藥理論指導(dǎo)下開展研究，制備方法應(yīng)與古代醫(yī)籍記載基本一致，改變工藝應(yīng)與“標(biāo)準(zhǔn)煎液”進(jìn)行對(duì)比研究，并充分考慮藥材來源、飲片炮制、制劑生產(chǎn)及使用等各個(gè)環(huán)節(jié)影響質(zhì)量的因素?！綢n terms of production craft,research should also be carried out under the guidance of the theory of TCM.The preparation method should be selected in accordance with the ancient records of medical books.The changed craftwork should be studied by comparing with the standard decoction and we should take full account of the factors affecting the quality,such as source of medicinal materials,processing,preparation and use.】

建議改變目前的中藥質(zhì)量控制體系。中醫(yī)理論指導(dǎo)下的中藥往往是多成分、多靶點(diǎn)共同起作用，采用任何一種活性成分均不能客觀地反映其整體的療效，中醫(yī)“辨證施治”用的是藥味而不是某一單一化學(xué)成分，這兩者之間完全是兩回事。如何選擇控制的化學(xué)組分并控制到多少限度是值得深思的問題。中藥的質(zhì)量標(biāo)準(zhǔn)應(yīng)與中醫(yī)的療效相關(guān)，中醫(yī)理論指導(dǎo)下的中藥標(biāo)準(zhǔn)化，是目前的難題之一。目前，日本、美國FDA、歐盟以及WHO均推薦采用煎液的指紋圖譜表征產(chǎn)品質(zhì)量的一致性，中藥的指紋圖譜可完整地表征中藥的整體特性，符合中醫(yī)整體作用的理論，值得我們借鑒?！綢t is proposed that the current quality control system of TCM be changed.Under the guidance of the theory of TCM,TCM often works through multiple components and multiple targets,which is why no single active ingredient can objectively reflect its overall efficacy.Treatment based on syndrome differentiation of TCM uses medicine rather than a single chemical component,which are totally two different things.How to choose the chemical components to control and how much to control are problems worth thinking.The quality standard of TCM should be related to the curative effect.The standardization of TCM under the guidance of the theory of TCM is one of the difficult problems to be solved now.At present,Japan,FDA in the US,European Union and WHO all recommend the fingerprint of decoction to represent the consistency of product quality.As fingerprint can fully represent the overall characteristics of TCM and is consistent with the theory of the overall role of TCM,it is worth learning from.】