左旋吡喹酮化学、药理和治疗日本血吸虫病的研究

本文报告了左旋、右旋和消旋吡喹酮的小鼠LD_(50)分别为2463、1344和2553mg/kg。右旋吡喹酮的毒性显著大于左旋与消旋吡喹酮。实验治疗证明,左旋吡喹酮是杀虫的有效成分,而右旋者则几乎无效。现场临床治疗左旋吡喹酮的剂量为单剂15和20mg/kg,治后6个月粪孵阴转率分别为86.0％和83.3％(P>0.05)。左旋和消旋均为单剂30mg/kg,治后3月和6月的阴转率,左旋分别为85.2％与87.7％,与消旋的疗效(72.1％与73.6％)比较有非常显著性差异(P<0.01)。采用左旋30mg/kg(单剂)与消旋50mg/kg(单剂)与总剂量60mg/kg(二日疗法)进行比较。治后3月粪孵阴转率分别为78.33％、70.69％与73.47％(P>0.05)。左旋20mg/kg与消旋40mg/kg(单剂),配对双盲试验,治后4月和6月,左旋组的虫卵阴转率分别为94.9％与96.3％,与消旋组(97.1％与94.0％)比较则无显著性差异(P>0.05)。病人服药后副反应轻而少。结果提示左旋吡喹酮治疗轻、中度感染者的剂量可为吡喹酮剂量的一半,疗效相似。说明该药具有高效、毒性小、安全、疗法简便的优点,有助于大规模化疗的开展。

LEVOPRAZIQUANTEL CHEMICAL SYNTHESIS, PHARMACOLOGY AND THERAPY OF SCHISTOSOMIASIS JAPONICA IN ANIMALS AND HUMAN

By resolving intermediate form in synthesis of praziquantel (PZQ), levo-and dextro-PZQ in chemical pure form were obtained. LD_(50) of dextro-PZQ in mice was 1344 mg/kg, and it is the highest of the three (P<0. 01),while the levo-PZQ and PZQ were 2463 and 2553 rag/ kg. In experiment treatment in mice, the worm reduction rates of 250 and 417 mg/kg single dose were 50% and 71.9% in levo-PZQ but -5.9% and 4.3% in dextro-PZQ groups (P( 0. 01). Dextro-PZQ did not showed any differences with control group(P>0.05). Treatment in rabbits showed that the average number and length of worm in levo-PZQ group were much less and shorter than that of the other two groups. And there were also no differences between dextro-PZQ and PZQ. Pathologically, egg granulomas could be seen in all liver surface, and they were uneven, numerous and densely mosaic in appearance composing of eosinophilic abscesses in dextro-PZQ and PZQ groups but smooth liver surface with few scattered egg granulomas and mostly fibrot- ic nodules in form of pseudotubercles in leov-PZQ group. Comparative field trials on human treatment with levo-PZQ and PZQ were undertaken in Sichuan, Hubei, and Jiangxi provinces independently. There were 546 patients treated with levo-PZQ and 372 cases with PZQ. The therapeutic efficacy of levo-PZQ was remarkabaly supperior to PZO. The side-effects were mild and transient.