摘要
目的:观察参元片的急性毒性和长期毒性,评估参元片用药安全性。方法:小鼠24 h内1次灌胃给药,测定药物的半数致死量(LD50)。连续观察14 d,记录动物外观、行为活动、精神状态、呼吸变化、中毒反应及死亡情况;存活小鼠每天记录体重及饲料量。参元片3个剂量组分别为生药6.48,12.96,32.40 g.kg-1,灌胃给予大鼠,连续给药6个月,停药恢复1个月,分阶段观察大鼠的一般行为、体重增长、食量消耗、血液学及血液生化学指征、尿常规检查、心电图、系统尸解及组织病理学检查。结果:参元胶囊小鼠LD50为生药97.46 g.kg-1,相当于临床成人日用剂量(0.171 g.kg-1)的568倍。长期毒性实验中,与同期对照组比较,参元片低、中、高3个剂量组动物行为活动、进食量、心电图等检查均未见异常;血液学指标、血液生化指标和尿液指标及未发现与供试品有关的异常改变,病理组织学检查发现参元片中剂量仅肝、肾系数高于对照组,恢复期时与对照组比较无明显差异,无迟缓毒性;高剂量连续给药6个月,肝、肾系数明显高于对照组,并出现软便。结论:参元片低剂量为安全剂量;高剂量连续给药可能对肝、肾功能有一定的影响,建议临床研究予以注意。
Objective： To study the acute and chronic toxicity of Shenyuan tablet. Method： Shenyuan tablet was intragastrically administered a time to mice in range of one day. Determine the median lethal dose （LD50）. Animal appearance, behavior, mental status, respiratory changes and the number of animals poisoned and die in each group were noted daily for 14 consecutive days. The amount of weight and feed of survived mice were recorded every day. The chronic toxicity was performed in rats, the treatment groups （minimum, middle, maximum dose of Shenyuan tablet. ） and control group were made. After continuously feeding rats orally for 6 months, we observed the rats behavior, weight gain, food consumption, blood test, biochemistry test, urine test, electrocardiogram, systematic autopsy and pharmacology test. The above physiological signs were inspected again 1 month after cease of feeding. Result： The oral acute toxicity study of Shenyuan tablet. In mice revealed that the maximum dose is 97.46 g kg-1, which was 568 times the maximum recommended human dose in the clinic practice. No significant differences were observed in rat＇s behaviors, food intake, electrocardiogram and relative examination indexes among the 3 different dosage groups of Shenyuan tablet. Which compared with normal control group. There was no abnormal condition for the results of blood test, biochemistry test, urine test and pharmacology test for the rats. The liver and kidney weight and liver （kidney） /rat weight have significant increase in the group of Shenyuan tablet maximum dose. And the feces are soft. Conclusion： The minimum dosage of Shenyuan tablet. is relatively safe. The shenyuan table, especially at high doses, may lead to potential liver and kidney toxic risk,so it should be paid attention in clinical studies.
出处
《中国实验方剂学杂志》
CAS
北大核心
2013年第2期276-282,共7页
Chinese Journal of Experimental Traditional Medical Formulae
基金
国家科技部重大新药创制项目(2009ZX09103441-002)
关键词
参元片
急性毒性
长期毒性
Shenyuan tablet
acute toxicity
chronic toxicity
