【邁克爾·司拜丁:博士，IUPHAR秘書長(zhǎng)，法國(guó)司拜丁研究所所長(zhǎng)；主要研究方向：藥理學(xué)，藥物研發(fā)，認(rèn)知的腦回路，應(yīng)激與精神病學(xué)及疾病、免疫和炎癥的影響?！?/p>

【謝里·文萊特：博士，英國(guó)羅伯特戈登大學(xué)教授，天然產(chǎn)物研究中心主任；主要研究方向：應(yīng)用廣泛的細(xì)胞、體外和體內(nèi)心血管疾病模型探討心血管病理學(xué)中正常生理機(jī)制的改變，特別是對(duì)飲食影響的反應(yīng)?！?/p>

【瓦拉瑞·西里可斯：博士，IUPHAR天然藥物藥理分委會(huì)副主席，法國(guó)斯特拉斯堡大學(xué)教授；主要研究方向：心血管藥理學(xué)，特別是在健康和疾病狀態(tài)下，如高血壓、糖尿病和生理性衰老中，內(nèi)皮調(diào)控血管內(nèi)穩(wěn)態(tài)的關(guān)鍵作用?！?/p>

Natural products(NPs)have always been rich sources of drugs,but there is also a great need for evidence-based medicine as NPs can also have side-effects.Therefore,therapeutic benefit must also be proven unless agents are nutraceu?ticals,food additives or foods.In Europe and USA,centuries of use of TCM for certain diseases must be reinforced by clinical evidence approved by regulatory authorities in the relevant countries.The world is split in healthcare and in therapies between NPs,traditional medicines,and new chemical entities.NPs need evidence-based medicine,both preclinically for their pharmacoki?netics,chemical structures,pharmacological drug targets,approved clinical effects for widespread acceptation.How?【天然產(chǎn)物是藥物研發(fā)的豐富來(lái)源，但由于天然產(chǎn)物的副作用，循證醫(yī)學(xué)研究是必要的。因此除非是保健品、食品添加劑或食物，其他藥物的療效必須被證明。在歐洲和美國(guó)，盡管中藥治療疾病已經(jīng)應(yīng)用了幾個(gè)世紀(jì)，仍然必須得到相關(guān)國(guó)家監(jiān)管部門批準(zhǔn)的臨床證據(jù)的支持。有關(guān)利用天然產(chǎn)物、傳統(tǒng)藥物還是新化合物進(jìn)行醫(yī)療保健和治療疾病這個(gè)問題，全球還未達(dá)成共識(shí)。天然產(chǎn)物需要循證醫(yī)學(xué)的支持，包括臨床前藥代動(dòng)力學(xué)、化學(xué)結(jié)構(gòu)、藥物作用靶標(biāo)及經(jīng)過驗(yàn)證的臨床療效等，才能被廣為接受。但是應(yīng)該怎樣做呢？】

Perhaps,by using the same way as IUPHAR structured modern pharmacology using its Nomen?clature Committee(NC-IUPHAR),creating expert subcommittees and having six-monthly meetings with published reviews in high impact journals with clear recommendations would achieve the desired outcome.NC-IUPHAR has now＞100 committees of 860 experts,125 expert reviews which have an h-index of 80 and has authoritative databases on all drug targets(www.guidetophar?macology.org and the new www.guidetoimmuno?pharmacology.org).The IUPHAR Natural Products Database Committee could expand its scope and membership to become a worldwide instrument for the promotion of evidence-based medicine for natural products and TCM.【可能借鑒IUPHAR應(yīng)用命名委員會(huì)（NC-IUPHAR）構(gòu)建現(xiàn)代藥理學(xué)的方法，建立專家分委會(huì)，每6個(gè)月召開高影響因子雜志發(fā)表的綜述的會(huì)議，并給出明確的建議，有望獲得預(yù)期效果。NC-IUPHAR有100多個(gè)委員會(huì)，860名專家，125個(gè)專業(yè)綜述，h因子達(dá)到80，還有權(quán)威的藥物靶點(diǎn)數(shù)據(jù)庫(kù)（www.guidetopharmacology.org和www.guidetoimmunopharmacology.org）。IUPHAR天然產(chǎn)物數(shù)據(jù)庫(kù)委員會(huì)應(yīng)該擴(kuò)大其范圍和成員，成為促進(jìn)天然產(chǎn)物和傳統(tǒng)中藥循證醫(yī)學(xué)發(fā)展的世界性工具?！?/p>

1 Difficulties（難點(diǎn)）

Because of recent events，some early studies performed in China must be validated.Furthermore,animal studies may not always be predictive.Many western medicines are single substances and complex mixtures may be viewed with a certain suspicion,because of the difficulty of maintaining quality and reproducibility,and also because certain of the ingredients may be harmful to sensitive individuals,and it is not easy to ascertain which substances apport benefit.In the past,contami?nation with insecticides,herbicides or heavy metals was also a genuine difficulty with some traditional products produced in developing countries,but that has been improved.One difficulty in Europe and the US,which is rarely mentioned,is public appreciation of traditional medicine concerning the environmental impact,and clear separation of traditional medicine from the inclusion of items from animals and fish which are environmentally threatened.【因?yàn)榻臧l(fā)生的一些事件，中國(guó)的一些早期研究必須要驗(yàn)證。此外，動(dòng)物研究并不總是具有預(yù)測(cè)性。許多西藥是單一物質(zhì)，而因?yàn)閺?fù)雜的混合物很難保持質(zhì)量和重現(xiàn)性，其某些成分對(duì)敏感個(gè)體有害，以及確定混合物中有益物質(zhì)的困難，所以總是對(duì)復(fù)雜的混合物持有懷疑。過去，殺蟲劑、除草劑和重金屬污染也是發(fā)展中國(guó)家一些傳統(tǒng)產(chǎn)品生產(chǎn)的真正難題，但是這種狀況已經(jīng)好轉(zhuǎn)。在歐洲和美國(guó)較少提及的一個(gè)難題是公眾對(duì)傳統(tǒng)藥物對(duì)環(huán)境影響的認(rèn)識(shí)，及把傳統(tǒng)藥物與列入受環(huán)境威脅的動(dòng)物和魚類等明確區(qū)分開。】

Another difficulty for research on NPs is the non-standardised application of the Nagoya protocol.The difficulty is that scientists wishing to use NPs must use due diligence before starting experiments.Nations are very rapidly defining restrictive laws on use of genetic material,which includes NPs,but which are made by politicians and lawyers with little knowledge of the pharmacological impli?cations of their propositions,and where the term"biodiversity"is a"passe-partout".Thus it is very difficult to be compliant throughout the world.This is a particular difficulty for patents to be globally compliant for all countries with a single Patent Cooperation Treaty(PCT).【另一個(gè)天然產(chǎn)物研究的難點(diǎn)在于《名古屋議定書》的非標(biāo)準(zhǔn)化應(yīng)用。困難在于，想要應(yīng)用天然產(chǎn)物的科學(xué)家在開始試驗(yàn)前必須付出很多努力。各國(guó)正在迅速制定關(guān)于遺傳資源，包括天然產(chǎn)物使用的限制性法律。這些法律是由政客和律師制定的，但是他們對(duì)藥理學(xué)含義知之甚少。“生物多樣性”這個(gè)術(shù)語(yǔ)是一把“萬(wàn)能鑰匙”，因此很難在世界范圍內(nèi)做到遵紀(jì)守法。特別是世界各國(guó)僅用專利合作條約（PCT）來(lái)保持專利全球兼容性是非常困難的?！?/p>

2 Opportunities（機(jī)遇）

However,clinical testing gives opportunities to extend clinical studies to other indications,and to enrich Chinese science with Western tech?nology-and vice versa!【然而，臨床試驗(yàn)為擴(kuò)展臨床適應(yīng)證，用西方的技術(shù)豐富中國(guó)的科學(xué)，提供了機(jī)遇，反之亦然?！?/p>

However,the FDA has only approved herbal mixtures as drugs for rare/orphan indications:green tea extracts for genital warts;FulyzaqR(now MytesiR)for diarrhoea in HIV/AIDs.Thus,proven efficacy in orphan diseases may be a key way for developing herbal mixtures/traditional medicines.It may be easier to develop TCM for such indications with simple and clear clinical endpoints rather than going for major markets such as Alzheimer disease,where so many drugs have failed.Furthermore,some modern technological advances allow a new vision of NPs and TCM which may create a cultural and scientific revolution.In this respect，biosynthesis of NPs,or of mixtures,may be a useful way forward by introducing biosynthetic genes into bacteria and yeast to produce the relevant substances.Metabolomics can also define the substances in complex mixtures and deconvolute screening programs on new targets.【到目前為止，F(xiàn)DA僅批準(zhǔn)了植物混合物作為藥物治療罕見病或孤兒病，如綠茶提取物治療尖銳濕疣，F(xiàn)ulyzaqR（MytesiR）治療艾滋病腹瀉。因而，證實(shí)治療孤兒病的有效性可能是開發(fā)植物混合物或傳統(tǒng)藥物的關(guān)鍵方法。針對(duì)類似有簡(jiǎn)單明確臨床終點(diǎn)的疾病開發(fā)傳統(tǒng)中藥可能更容易，而不是針對(duì)如阿爾茨海默病等疾病的主要市場(chǎng)，在此領(lǐng)域許多藥物都失敗了。此外，現(xiàn)代技術(shù)的進(jìn)步為天然產(chǎn)物和傳統(tǒng)中藥的研究提供了新的視角，可能引發(fā)科學(xué)和文化的革命。在這方面，通過將生物合成基因?qū)爰?xì)菌和酵母產(chǎn)生相關(guān)物質(zhì)，生物合成天然產(chǎn)物或混合物可能是有用的方法。代謝組學(xué)也能夠定義復(fù)雜混合物中的物質(zhì)，并對(duì)新靶點(diǎn)進(jìn)行反卷積篩選?！?/p>

Food products are also important.Professor SCHINI-KERTH showed the key importance of food and nutritional-derived products to protect the cardiovascular system and,hence,to retard the development of ageing-related major cardio?vascular diseases,the leading cause of death worldwide.Adherence to the mediterranean diet characterized by the daily intake of polyphenolrich fruits and vegetables,cereals and a moderate consumption of red wine,a weekly intake of fish,white meat and eggs,and a monthly intake of red meat was associated with a 9%reduction in mortality from cardiovascular diseases and a 6%in the incidence of or mortality from cancer.Regular consumption of red wine resulted also in a 36%reduction of the relative risk of cardiovascular diseases.The health benefit of these dietary products has been related to their high content of polyphenols.Experimental studies using a red wine extract(Vin de Corbières;2.9 g·L-1of poly?phenols)indicated that red wine polyphenols,a mixture of more than 800 compounds including flavanols,anthocyanins and phenolic acids,are potent stimulators of the endothelial formation of vasoprotective factors including nitric oxide and endothelium-dependent hyperpolarization.Similar effects were also observed in response to grape skin polyphenols and a grape juice indicating that the bioactive compounds originate from the fruit.Moreover,a superior vasoprotective effect was observed with juices and purees from aronia,blackcurrant,blueberry,cranberry and lingonberry compared to grape juice.The potential of nutri?tional-derived polyphenols to protect the cardio?vascular system is also indicated by the fact that intake of red wine polyphenols prevented angio?tensin II-induced endothelial dysfunction in an experi?mental model of hypertension,and improved flowmediated vasodilatation in humans.Thus,poly?phenol-rich natural products appear to be an inter?esting approach to protect the cardiovascular system.In this respect,the difference between Food-Dietary and Supplement-Drug is important.The dietary supplement category is limited to oral route of administration;if skin application,then it is regu?lated as a cosmetic.The FDA has recently published guidelines for"New Dietary Ingredi?ents"(NDIs).These are not yet implemented,but the intent is that companies introducing dietary supplement products containing an ingredient that was not marketed in the US prior to Oct 15,1994,must provide NDI notification to the FDA prior to marketing,with the basis for reasonable expectation of safety.【食物也是藥物的重要來(lái)源。衰老相關(guān)的心血管疾病是世界范圍內(nèi)的主要死因，SCHINI-KERTH教授展示了食物和營(yíng)養(yǎng)衍生產(chǎn)品在保護(hù)心血管系統(tǒng)而延緩衰老相關(guān)心血管疾病發(fā)展上的重要性。堅(jiān)持地中海式飲食，包括每天食用富含多酚的水果、蔬菜、谷物和飲用適量紅酒，每周吃魚、白肉和雞蛋，每月食用紅肉，可使心血管疾病死亡率降低9%，癌癥發(fā)病率或死亡率降低6%。經(jīng)常飲用紅酒可使患心血管疾病的相對(duì)風(fēng)險(xiǎn)降低36%。這些食品對(duì)健康有益與其富含多酚有關(guān)。對(duì)紅酒提取物（科比埃酒，含多酚2.9 g·L-1）的實(shí)驗(yàn)研究顯示，紅酒多酚是含有包括黃烷醇、花青素、酚酸等800余種化合物的混合物，是一氧化氮和內(nèi)皮依賴性超極化等內(nèi)皮血管保護(hù)因子形成的強(qiáng)力刺激劑。在葡萄皮多酚和葡萄汁上也觀察到了相似的結(jié)果，表明具有生物活性的化合物來(lái)源于葡萄果實(shí)。而且，與葡萄汁相比，野櫻莓、黑加侖、藍(lán)莓、紅莓和林果莓的果汁和果泥血管保護(hù)效果更好。攝入紅酒多酚可阻止高血壓實(shí)驗(yàn)?zāi)Ｐ脱芫o張素Ⅱ誘發(fā)的內(nèi)皮功能紊亂，也可改善人的血管擴(kuò)張，這些都表明營(yíng)養(yǎng)衍生的多酚具有保護(hù)心血管系統(tǒng)的潛力。因此，富含多酚的天然產(chǎn)物是一種保護(hù)心血管系統(tǒng)的有趣方法。從這方面來(lái)看，將食物、膳食補(bǔ)充劑和藥物進(jìn)行區(qū)分是重要的。膳食補(bǔ)充劑僅限于口服途徑，如果應(yīng)用于皮膚，則被作為化妝品管理。美國(guó)食品藥品管理局最近發(fā)布了新膳食成分（New Dietary Ingredients′，NDI）指南。雖然尚未實(shí)施，但它的目的是如果膳食補(bǔ)充劑采用的成分1994年10月15日前未在美國(guó)上市，公司必須在市場(chǎng)推廣之前向FDA提供NDI通知，并以合理的安全預(yù)期為依據(jù)?！?/p>

3 A way forward for China（中國(guó)的前進(jìn)方向）

We were impressed by the move of the Chinese Government to invest heavily in innovative phar?maceutical research,with the aim of increasing innovation and making China a key player in the global Pharma"space".China has a rich history in the use of TCMs and following our visit to the Jiangsu Kanion Pharmaceutical Company in Lianyun?gang we were highly impressed by the strides being made to isolate and manufacture to a high quality TCMs for use in traditional medicine.This is clearly a highly innovative business,as judged by the large number of patents generated and the focus on quality control.However,for China to make a serious impact in the global pharma market with their TCM preparations,there is a need to address the key regulatory requirements that are already imposed upon western medi?cines.These include providing solid scientific evidence of the mechanism of action by which the TCMs exert their therapeutic effects,followed by well designed clinical trials to provide sound indica?tion of clinical benefit.【中國(guó)政府大力投資創(chuàng)新藥物研究的舉措給我們留下了深刻的印象，旨在加大創(chuàng)新力度，使中國(guó)成為全球制藥“空間”的重要力量。中國(guó)在應(yīng)用傳統(tǒng)中藥方面有悠久的歷史，在參觀連云港江蘇康緣藥業(yè)有限公司后，我們對(duì)從傳統(tǒng)中藥中分離和制造高品質(zhì)中藥取得的長(zhǎng)足進(jìn)步深表贊嘆。從獲得的大量專利和對(duì)質(zhì)量控制的關(guān)注可以看出，康緣藥業(yè)有限公司是一個(gè)高度創(chuàng)新的企業(yè)。然而，中國(guó)想要通過中藥在全球制藥市場(chǎng)產(chǎn)生重大影響，需要解決西藥現(xiàn)有的關(guān)鍵監(jiān)管要求，包括為中藥療效作用機(jī)制提供堅(jiān)實(shí)的科學(xué)依據(jù)，并設(shè)計(jì)完善的臨床試驗(yàn)，為臨床使用提供合理的提示?！?/p>

The documentation detailing the Lianyungang Talent Policy provided very interesting reading and demonstrated a keen desire to encourage and support innovation and entrepreneurship within the academic community,with the inten?tion of bringing their expertise into local SME′s.The financial support is highly commendable and should serve as a good incentive to academic/business partnership working.However,perhaps there is an additional opportunity to increase the number of companies by encouraging academics to take their innovative ideas and discoveries and "spin out"companies from within the University base.To support this skills develop?ment,rather than financial incentive,could be the key whereby training in creating a business plan,identifying market needetcwould assist academicsinthetransformationfrom being"business facilitators"to"business creators".【連云港人才政策非常詳細(xì)，可讀性極佳，體現(xiàn)了學(xué)術(shù)界鼓勵(lì)和支持創(chuàng)新和創(chuàng)業(yè)精神的強(qiáng)烈愿望，目的是把人才的專業(yè)知識(shí)輸入當(dāng)?shù)氐闹行∑髽I(yè)。財(cái)政支持值得稱道，激勵(lì)了學(xué)術(shù)/商業(yè)合作。此外，鼓勵(lì)大學(xué)采納公司的創(chuàng)新觀點(diǎn)和發(fā)明，在大學(xué)基地內(nèi)拆分公司也是增加公司數(shù)量的機(jī)會(huì)。支持技能的發(fā)展，而不是經(jīng)濟(jì)激勵(lì)，可能是至關(guān)重要的，培訓(xùn)制定商業(yè)計(jì)劃、確定市場(chǎng)需求將有助于學(xué)者從“為企業(yè)服務(wù)”轉(zhuǎn)變?yōu)椤皠?chuàng)建企業(yè)”?！?/p>