伊维菌素微乳制剂的安全性试验

Safety Test of Ivermectin Microemulsion

按照《中国兽药典》2010版和《兽药及添加剂安全性毒理学评价程序》的要求,对伊维菌素微乳制剂进行肌肉刺激性试验、热原试验和注射途径LD50测定,为其临床应用提供安全性依据。肌肉刺激性试验,观察4只家兔注射伊维菌素微乳制剂后48h的变化;热原试验,测家兔的体温变化,判断伊维菌素微乳制剂所含热原的限度是否符合规定;LD50测定,分别给大鼠、小鼠按组一次腹腔注射不同剂量的伊维菌素微乳,连续观察7d^14d,记录各组动物急性毒性反应的症状、病理变化、死亡时间,按简化寇氏法计算其半数致死量(LD50)及95%可信限。结果表明,伊维菌素微乳制剂对家兔股四头肌未见明显刺激作用;热原限度符合规定,无致热源;伊维菌素微乳制剂对大鼠、小鼠腹腔注射的LD50为其临床推荐用量(0.2 mg/kg)的191.28倍和161.00倍,并且高于伊维菌素原料药的LD50(24.249 3mg/kg)。伊维菌素微乳制剂的安全性试验结果提示其安全可靠。

This experiment was conducted to evaluate the reliability of ivermeetin microemulsion injection by testing the muscle stimulation, pyrogen test and acute toxicity test according to 2010 edition of Chinese Veterinary Pharmacopoeia. In the muscle stimulation test, four rabbits were observed for 48 h after injec- ting ivermectin microemulsion injection. In the pyrogen test,temperature changes were detected in rabbits to test the pyrogen of ivermectin microemulsion The different dosages of ivermectin microemulsion were used to mice and rats by intraperitoneal injections then mice and rats were observed seven to fourteen days s the acute toxical symptoms, pathological lesions, death time were observed and the LD80 and 95% confi- dence limit was calculated by simplify Karber method. The results showed that there were no significant stimulation to muscles The pyrogen test of ivermectin microemulsion was negative and its pyrogen accords with the standard limitation The LDs0 of ivermectin microemulsion by intraperitoneal injection in mice and rats are higher than that of ivermectin injection （24. 249 3 mg/kg）. These results indicated that ivermectin microemulsion is safe and reliable based on the animal experiments.