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    這支團隊破解了中藥藥效表征難瓶頸

    發布單位:人員機構 [2019-05-16 00:00:00] 打印此信息

    在3月27日廣東省委、省政府召開的全省科技創新大會上,我校藥學院中藥及天然藥物研究所何蓉蓉教授團隊與廣州白云山敬修堂藥業股份有限公司等單位合作完成的“基于疾病易感性的中藥藥效評價及應用”項目斬獲廣東省科技進步一等獎。該項目跳出傳統的西醫西藥評價方法,在“情志致病”中醫理論的指導下,以“疾病易感性”為突破口,采用多種心理應激模型建立“情志因素”誘發疾病易感性實驗動物模型,在明確藥效表征的基礎上解析了產品的活性部位和成分,創新和建立了適合中藥作用特點的藥效評價方法。

    這一評價方法解決了中藥藥效表征難的瓶頸問題,在推進中醫藥現代化、國際化上邁出了重要一步。運用此技術評價方法,該團隊對中藥大品種進行二次開發和成果推廣,有效指導了臨床醫生用藥,提高了產品質量標準,實現了產品升級,產生了明顯的經濟效益:完成單位和推廣應用單位相關產品近三年銷售額97.3億元,利潤15.4億元。

    (何蓉蓉教授在進行實驗研究)

    直面中藥表征難瓶頸 基于“舊法” 創建中藥藥效評價方法

    “熱銷中藥產品清熱消炎寧膠囊、抗病毒口服液都是抗外感疾病的藥物,臨床有效,但用現代藥理學抗病毒的方法評價無效,我們就考慮,是否選擇了合適的藥效評價模型可能是其中的主要原因。”何蓉蓉說。

    循著這一思路,團隊從中醫的病因理論“情志致病”中找到了靈感,提出了“疾病易感性”的概念,即人的心情狀態不同,對同一個疾病的易感性就不同。

    為了驗證清熱消炎寧是否通過調節自身對疾病的易感性、來達到抗流感的作用,團隊以100只實驗小鼠為樣本,通過一步步的實驗,最后發現:一般情況下,當感染一定滴度的病毒時,60%小鼠會出現流感病癥,說明個體存在易感性差異;如果對實驗動物進行情志應激以后,再讓它們感染同樣滴度的病毒,則幾乎100%小鼠都會出現流感的癥狀,說明“情志因素”會誘發疾病易感性。基于此,何蓉蓉團隊創新性地提出了適合中藥抗流感病毒作用評價的病毒易感動物模型。

    通過這一模型,團隊成功地評價了清熱消炎寧等中藥藥效,并建立了符合中藥作用特點的“疾病易感”藥效評價體系。相關研究成果已獲7項專利授權。其中,發明專利"九節茶提取物在降低流感病毒易感性上的應用"獲得國家知識產權局頒發的第十七屆中國專利優秀獎。

    “我們一直以來都在使用國際通用的藥效評價模型,一直無法說清楚‘清熱消炎’這個概念,以及清熱消炎寧膠囊的具體藥效。現在我們的中醫藥也終于有了自己的一套評價體系,解決了臨床醫生用藥困惑的問題,同時為我們的中醫藥藥效的明確、質量標準的把控提供了保障和動力!”何蓉蓉感慨道。

    產學研合作促進企業產品升級和新藥研發 助力中藥國際化和現代化

    現代藥理學上沒有“清熱消炎”概念、具體藥效說不清楚、臨床醫生用藥困惑……這不只是清熱消炎寧膠囊的生產廠家敬修堂藥業一家企業的問題,而是我國推進中醫藥現代化和國際化過程中遇到的普遍性問題。

    而這其中的關鍵正是對中藥藥效作用的客觀說明。由于中西方文化的差異,采用經典的西醫西藥評價方法難以體現名優中藥的藥理活性。中醫藥產品無法完成藥效評價和表征,直接導致了其陷入“科學內涵欠缺”“臨床無法指導用藥”“患者不能放心服用”的困境。因此,回答和解釋傳統中藥的作用效果的首要任務是創新和建立適合中藥作用特點的藥效評價方法。

    運用疾病易感評價體系,何蓉蓉團隊有效表征了清熱消炎寧的藥效,同時構建了活性相關的指紋圖譜,提高了藥品生產工藝和質量標準,進行了產品升級。2012年,該藥獲得國家食品藥品監督管理局頒發的《藥品補充申請批件》。此前面臨銷售困境的清熱消炎寧膠囊,終于峰回路轉。

    這一研究成果是包括姚新生、栗原博、何蓉蓉等兩代人持續奮斗十多年的成果。2004年,我校藥學院姚新生院士即牽頭廣州市重大課題《廣州地區清熱解毒類名優中成藥作用靶標及作用物質基礎研究》,重點攻關中藥科學內涵的闡明,尋找一個新的理論體系來解釋中藥藥效表征的問題。

    何蓉蓉團隊開展產學研合作項目16項,獲省部級以上項目15項。廣州白云山敬修堂藥業股份有限公司只是團隊的合作企業之一。依托“985創新藥物研究優勢學科平臺”“中藥藥效物質基礎及創新藥物研究廣東省高校重點實驗室”等基地和平臺,團隊長期致力于天然藥物及中藥現代化的研究,與廣州王老吉藥業股份有限公司、香雪制藥股份有限公司等多家知名中藥生產企業開展了長期的產學研合作,促進了部分藥品的二次開發,與中醫藥傳統文化的進一步傳播。

    “除了感染性疾病,疾病易感性評價體系也同樣適用于抗腫瘤、現代神經退行性疾病、心血管疾病等類別的中藥藥效評價。”何蓉蓉說。團隊正服務更多類別的臨床中藥產品,同時“兩條腿走路”,進行原創性新藥創制研究。針對該項目的未來發展,團隊有著更大的目標。“我們希望能把中醫藥推廣到國際市場中去。”

    目前,該科研項目在國內外學術會議做邀請報告30余次;發表SCI論文95篇,總他引2345次。通過論文和會議讓這一成果在國際國內廣泛傳播,這是他們把中藥推向國際的第一步。

    在與何蓉蓉團隊合作的相關企業中,廣州白云山敬修堂藥業的產品是其中最有望在歐盟注冊的。他們正致力將清熱消炎寧膠囊推向國際市場。“目前這個大背景下,中藥國際化很難。但中醫藥是我們民族的獨特產業,我們會盡最大努力去做。”何蓉蓉說。

    科研與生活:“能離多近,就離多近”

    十五年磨一劍實為不易。從2004年立項摸索,到創建中醫藥藥效評價體系,再到成果應用轉化為良好經濟效益,何蓉蓉也從一名博士生,逐漸接過項目,成長為獨當一面的項目帶頭人。與何蓉蓉一樣,通過這個項目一同成長的,還有藥學院20名博士生和45名碩士生。

    回憶起科研道路,何蓉蓉直言:“大家都非常非常努力。”自2004年加入該科研團隊以來,大家都似乎有一個共識:住得離實驗室越近越好。為了能夠隨時回實驗室監測數據、修改方案等,工作后的何蓉蓉從校外搬到校內。“吃飯時能夠經過實驗室,散步也能散到實驗室,甚至我生了寶寶坐完月子又馬上回到了實驗室。”

    如今,更多年輕人才加入研究團隊,何蓉蓉認為這是一種傳承:“我的辦公室旁邊就是姚新生教授和栗原博教授的辦公室,每每經過我的門口,他們總要停下來對我叮嚀幾句,有他們‘盯著我’,我覺得很安心很有動力。這可能就是姚教授常掛在嘴邊的‘培培土、扶扶正’的精神。”

    (新聞中心 李偉苗 學生記者 王嘉琪)


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