莽吉柿胶囊的急性毒性和长期毒性研究

Acute Toxicity and Long-term Toxicity Study of The Mangosteen Capsule

为进一步确定莽吉柿胶囊的安全性,通过大鼠、小鼠灌胃给药,观察其急性毒性和长期毒性反应,为该药的临床前安全性评价、临床剂量设计和临床毒副反应监测提供参考依据。急性毒性实验:小鼠灌胃给药(28.8g/kg、40mL),1d 2次,给药间隔时间5 h,观察记录给药后14 d内动物中毒症状、死亡时间和体重;解剖死亡动物和存活动物,观察主要脏器变化。长期毒性实验:设置莽吉柿胶囊低(0.15 g/kg)、中(0.9 g/kg)、高(5.4 g/kg)3个剂量组和溶剂对照组,给药26周,观察记录动物的外观行为、体重和摄食量,并分别于给药后第4周、13周和26周恢复期结束后进行血液学、血液生化学及病理组织学检查。急性毒性实验,给药后有2只动物死亡,解剖没有发现脏器存在明显异常,其余动物未见异常。长期毒性实验,给药期内高剂量组动物摄食量、体重与对照组比较呈显著性差异,恢复期结束后恢复正常,无延迟性毒性反应,与对照组无显著差异。莽吉柿胶囊单次灌胃最大耐受剂量> 28.8 g/kg,大鼠灌胃26周无毒反应剂量为0.9 g/kg,分别相当于临床拟用剂量的576倍和18倍,结果表明,临床拟用剂量安全。

In order to further determine the safety ofMangosteen Capsule, acute toxicity and long-termtoxicity were observed by intragastric administration in rats and mice. The preclinical safety evaluation, clinical dose design and clinical toxicity were observed. Monitoring provides a basis for reference. Acute toxicity observation: Mice were intragastric administration twice a day, acute toxicity of The Mangosteen Capsule on 14 days after the administration was observed, the general parameters and major organs of mice were measured. Long-termtoxicity observation:160 Wistar rats were randomly divided into four groups: low, middle and high dose group(0.15 g/kg,0.9 g/kg ,5.4 g/kg) and negative control group. All rats were administrated for 26 weeks and then recovered for 4 weeks,recorded food intake and body weight weekly. 1/3 rats were killed after 13 weeks, 26 weeks and the remaining recovered for 4 weeks. The hematological and biochemical parameters and histopathology of major organs were measured. Result Acute toxicity observation: 2 mice were dead in the experiment and anatomy of the 2 dead mice showed no significant effect on organ pathological morphology. Long-termtoxicity observation: There was significant influence of TheMangosteen Capsule in the 5.4 g/kg group on food intake and body weight. The 5.4 g/kg group mice returned to normal after drug withdrawal and no histopathological lesions were observed in animals.The largest amount of The Mangosteen Capsule for mice was 28.8 g/kg, which was 576 times of clinical dose administration. The no-observed-adverse-effect levels for rats were considered to be 0.9 g/kg, which was 18 times of clinical dose administration. The Mangosteen Capsule isn’t found long-termtoxicity and acute toxicity in the experiment condition, it suggested The Mangosteen Capsule has a good clinical safety.