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CN101856355A 阿的平及其代用品对乙型病毒性肝炎的治疗作用 无效 - 撤回

阿的平及其代用品对乙型病毒性肝炎的治疗作用
摘要：
该研究发现属于药物研究开发应用于抗HBV研究领域。本发明和发现公布了阿的平以及阿的平的同类药物咯萘啶具有强大地抗HBV生物学活性。该项研究通过使用荧光定量PCR、荧光定量RT-PCR、HBV DNA定量、HBsAg定量、HBeAg定量、cccDNA定量、Northern blot、Southern blot、Western blot、免疫组织化学等方法，在治疗剂量范围内长期(30天～60天)使用维持剂量能够使HepG-2.2.2.15细胞培养上清HBV DNA、HBsAg、HBeAg完全消失，细胞内HBsAg、HBeAg、HBcAg等完全转阴，HBV DNA呈高度抑制状态，HBV cccDNA完全呈阴性，荧光定量RT-PCR检测发现细胞内表达HBsAg和HBcAg抗原的mRNA完全呈阴性，另外其疗效是目前临床上抗HBV一线药物拉米夫定30倍左右。为了阐明阿的平以及阿的平的同类药物咯萘啶作用机制，将HBV基因组分成3个片段分别插入到虫荧光素酶报告载体PGL3上Xb1位点，多功能酶标仪检测发现虫荧光素酶发光值显著减少，说明阿的平以及阿的平的同类药物咯萘啶分子可以和细胞内HBV DNA非特异性结合从而抑制了该病毒的复制，使之在子代复制的细胞中HBV DNA含量减少以致消失。该项研究在国际上首次提出使用阿的平以及阿的平的同类药物咯萘啶能够治疗HBV的新理论且效果特别明显，能够完全抑制和杀灭细胞内HBV。开创了人类使用新型的化学药物抗病毒治疗的新局面，获得了中国具有自主知识产权的抗HBV一类新药。该申请专利要求保护3个相连苯环结构(称为吖啶环)和CH3O-、-NH-、CL-等基团在临床上用于抗HBV病毒治疗。
摘要（英）：

By adopting methods of fluorescent quantitation PCR, fluorescent quantitation RT-PCR, HBV DNA quantitation, HBsAg quantitation, HBeAg quantitation, cccDNA quantitation, Northern blot, Southern blot, Western blot, immunohistochemistry, and the like in the research and using the maintenance dose within the treating dose range for a long time (30-60 days), supernatant HBV DNA HBsAg HBeAg cultured by HepG-2.2.15 cells can completely disappear, HBsAg, HBeAg, HBcAg, and the like in the cells are completely turned to be negative, HBV DNA is in a high inhibited state, HBV cccDNA is completely negative, fluorescent quantitation RT-PCR detection finds that the mRNA for expressing HBsAg and HBcAg antigens in the cells is completely negative, and in addition, the curative effect of the atabrine is 30 times that of lamivudine as a first-line drug for resisting HBV in current clinic. In order to illustrate the action mechanism of the atabrine and the pyronaridine as a drug belonging to the same kind with the atabrine, an HBV genome is divided into 3 segments which are respectively inserted into an Xb1 position on a luciferase report carrier PGL3, a multifunctional microplate reader detects and finds that the light production value of the luciferase is remarkably reduced, which shows that the molecules of the atabrine and the pyronaridine as a drug belonging to the same kind with the atabrine can be nonspecifically combined with the HBV DNA in the cells, thereby inhibiting the copying of the virus and ensuring that the HBV DNA content of the virus in cells copied by the filial generation is reduced till to disappear. The patent requires protecting the application of 3 linked benzyl structures (named as ethyleneimine) and radicals such as CH3O-,-NH-, CL-, and the like for resisting HBV virus in clinic.

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