灵芝扶正颗粒的毒理学研究

Studies on toxicity of Ling-Zhi-Fu-Zheng Granules

目的:观察大鼠和小鼠口服灵芝扶正颗粒的急性毒性和长期毒性作用,为临床试验设计人用安全剂量和主要观察指标提供参考。方法:以SPF级NIH小鼠进行最大给药量法的急性毒性试验;用SPF级SD大鼠进行长期毒性试验,192只大鼠按性别与体重随机分为低、中、高三个剂量组(灵芝扶正颗粒1.63、3.25、6.51g/kg)和一个空白对照组,每日按1.5ml/100g灌胃给药一次,每周给药6d,连续26周。结果:小鼠体重增长、摄食量与空白对照组相比较均无明显差异,试验过程中未见动物死亡,大体解剖也未发现组织器官出现体积、颜色、质地等病理改变。各组SD大鼠的外观体征、行为活动、粪便性状及摄食量等未见明显异常,体重正常增长,血液学和血液生化学检查未见与毒性作用相关的异常变化,病理剖检和组织检查均未见特征性的病理学改变。结论:小鼠口服灌胃灵芝扶正颗粒允许的最大耐受量为20g/kg,未观察到灵芝扶正颗粒(1.63￣6.51g/kg)对SD大鼠有特征性毒性作用,也未观察到其延迟性毒性作用。

Objective： To study on toxicity of Ling-Zhi-Fu-Zheng Granules for oral administration in rats and mice. Methods： The acute toxicity of Ling-Zhi-Fu-Zheng Granules was studied in NIH mice with most tolerance dose method （MTD）. 192 rats were randomized into low dosage group, moderate dosage group, high dosage group and control group to observe the chronic toxicity of Ling-Zhi-Fu-Zheng Granules, following 26 weeks continuum oral administration at a dosage of 1.5 ml per 100 g body weight per day in rats, general status, parameters of hematology, blood biochemistry and pathology-organize observation were measured to evaluate the toxicity. Results： Body weight and feedingstuff of mice had no evident difference comparing with control group at the dose of 20 g/kg, and died animals were not observed in the experiment; appearance, behavior, feces, body weight and feedingstuff of rats had no evident difference comparing with control group and, hematology, blood biochemistry and pathology-organize observation had also no evident abnormity changes in correlation with the drug. Conclusion： The MTD is 20 g/kg with single irrigation of Ling-Zhi-Fu-Zheng Granules in mice; the characteristic toxicity effect were not observed at a dosage of 6.51 g per1 kg body weight per day Ling-Zhi-Fu-Zheng Granules in rats.