按 Enter 到主內容區

CCMP102-RD-111 高氏柴胡防治C型肝炎病毒感染與應用安全性評估

  • 資料來源:中醫藥司
  • 建檔日期:102-07-25
  • 更新時間:109-02-18

林俊清 
高雄醫學大學 藥學系

全球目前有1億七千萬人左右感染C型肝炎病毒。現有的臨床治療藥物IFN/ribavirin相當昂貴且對於最普遍的 genotype 1 的治療效果並不理想(治癒率約50%)加上副作用大。雖2011美國FDA核准了兩個新藥boceprevir及telaprevir (HCV genotype 1 NS3/4A protease inhibitor),為患者帶來新希望,但無法單一治療只能與IFN/ribavirin合併使用,且對其他genotype(除了genotype 1)不適用的限制,仍無法完全解決IFN/ribavirin的問題。因此繼續開發C型肝炎病毒及其引起的肝病治療藥物乃是值得優先考慮的一大問題,為了研發經濟、有效且副作用少的抗C型肝炎藥物,本計畫採取台灣特有種高氏柴胡,同時也開發台灣本土生藥資源。 我們的成果中發現高氏柴胡其活性成分主要作用於抑制病毒的侵入(entry)。而我們發現BK-2為高氏柴胡中最有效的活性成分,因此更深入探討其與病毒醣蛋白的影響,證實BK-2能與C型肝炎病毒醣蛋白E2 (glycoprotein E2)作用而干擾病毒侵入細胞。另外BK-2除了可抑制JC1-HCVcc(genotype 2a),還能夠抑制基因型2b, 3a, 7a的C型肝炎病毒感染,證實其應用範圍可更廣,除了治療C型肝炎病毒感染及相關疾病外,甚至未來能應用於換肝手術中預防新的肝細胞被病毒感染,給予臨床應用相當大的幫助。 另一方面BK-2亦能防止第一型皰疹病毒(HSV-1)、麻疹病毒(MV)、呼吸道融合病毒(RSV)、呼腸孤病毒(RV)及登革熱病毒(DENV)侵入細胞,為廣效性的病毒侵入抑制劑(broad spectrum entry inhibitor),因此未來不只能夠開發為治療藥物,亦可應用在口罩、手套、防蚊液、洗手乳、乾洗手(消毒劑)、與各種清潔用品中,讓防疫工作變得更簡單。

關鍵詞:高氏柴胡、本土生藥、C型肝炎病毒、抗病毒藥物

Assessment of efficacy and drug application safety of Bupleurum Kaoi againsthepatitis C virus infection

Chun-Ching Lin School of Pharmacy, College of Pharnacy, Kaohsiung Medical University

A Approximately 170 million people are infected with hepatitis C virus (HCV) worldwide. The hepatotropic virus causes significant morbidity and medical socio-economic burden globally, including Taiwan. At present, there is no vaccine available for immunization against HCV. In addition, treatment with standard therapy (interferon with ribavirin) on the most common genotype 1 infection is suboptimal (50%), which is also associated with high cost and serious side effects. Although a new hope for genotype 1 patient about boceprevir and telaprevir which is HCV genotype 1 NS3/4A protease inhibitor were approved by FDA in May 2011, but the two drugs are unsuitable for monotherapy. This treatment must be combined with interferon-alfa and ribavirin. It is therefore necessary to develop novel anti-HCV therapeutics that are inexpensive, highly efficient, and that result in minimal side effects with high patient adherence. We have previously screened anti-HCV crude extractions from the natural medicinal plant Bupleurum kaoi (B. kaoi) that is acclimated for culture in Taiwan. Our first year study looked at the effects of the drug against the virus particle and its life cycle. Results demonstrated that BK and its different components inhibited HCV entry while leaving replication, translation, assemble, release, and cell-to-cell spread relatively unaffected. BK-2 is the active compound of highest SI in value from B. kaoi. Bk-2 influenced HCV glycoprotein E2 and blocked viral entry. On the other hand, BK-2 can inhibit other genotype viruses (2b, 3a, 7a) suggesting that it acts in a genotype-independent fashion. BK-2 also acted as an entry inhibitor against herpes simplex virus (HSV-1), measles virus (MV), respiratory syncytial virus (RSV), reovirus (RV), and dengue virus (DENV). These data also suggest that Bk-2 may possess broad-spectrum antiviral potential. Potential application of BK-2 may include coating of the drug on gloves, masks, insect repellent, hand wash gel, hand sanitizer, and detergent.