参苓健脾胃颗粒对幼龄大鼠的毒性研究  

Toxicity study for Shenling Jianpiwei Particles in juvenile rats

作　　者：荆宝琴[1,2] 张金晓 王磊[1,2] 谭琳 段蕊[1,2] 申秀萍 JING Baoqin;ZHANG Jinxiao;WANG Lei;TAN Lin;DUAN Rui;SHEN Xiuping(Tianjin Institute of Pharmaceutical Research New Drug Evaluation Co.,Ltd,Tianjin 300301,China;Tianjin Engineering Research Center of Drug Preclinical Assessment Technology,Tianjin 300301,China;Kunming Chinese Medicine Factory co.Ltd,650228,Kunming 650228,China)

机构地区：[1]天津药物研究院新药评价有限公司,天津300301 [2]天津市新药非临床评价技术工程中心,天津300301 [3]昆明中药厂有限公司,云南昆明650228

出　　处：《药物评价研究》2018年第9期1621-1629,共9页Drug Evaluation Research

摘　　要：目的评价幼龄大鼠重复ig给予参苓健脾胃颗粒后的毒性反应,为儿童的用药安全剂量及临床不良反应监测范围提供参考。方法 176只幼龄SD大鼠随机分为4组,即对照组和参苓健脾胃颗粒低、中、高剂量(3.3、9.9和22.2 g生药/kg)组,每天ig给药1次,连续给药3个月,停药恢复1个月;检查指标包括临床观察、体质量、摄食量、血液学、血液生化学、凝血功能、尿液生化、生长发育、自主活动、学习记忆能力、血清激素、脏器质量及系数、解剖检查和组织病理学检查。结果参苓健脾胃颗粒连续ig给药1个月及3个月检查,与对照组比较,除22.2 g生药/kg组雄性大鼠自给药21 d起至给药结束,大部分检测时间点平均摄食量明显降低(P<0.05、0.01)外,各剂量组其它各项指标未见与药物相关的毒性反应。结论参苓健脾胃颗粒重复ig给药3个月,对幼龄大鼠未观察到毒性反应的剂量(NOAEL)为22.2 g生药/kg,为5~14岁儿童临床最大拟用剂量(0.56 g生药/kg)的40倍,提示临床长期使用的安全性较好。Objective To investigate the toxic effect of Shenling Jianpiwei Particles（SLJPWP） in juvenile rats for evaluating its safe dosage in children and providing reference for monitoring its clinical adverse reaction. Methods Totally 176 juvenile SD rats（males and females） were randomly divided into four groups, control group and SLJPWP high, medium, and low dose（0, 3.3, 9.9, and 22.2 g crude drug/kg） groups. All animals were ig administered once daily for three months continuously, and then recovered for one month with no dosing. Parameters were examined including general condition, body weight, food intake, hematological and biochemical index, blood coagulation parameter, urine biochemical parameters, growing development, autonomous activity, learning and memory ability, hormone, organ coefficient, anatomic examination, and histopathological examination. Results Compared with control group, the average amount of food intake was decreased in 22.2 g crude drug/kg SLJPWP group in male rats from 21 d to the end of administration. No other drug-related toxic reaction was found in other indexes of SLJPWP granules. Conclusion After rats were ig administered with SLJPWP for three months continuously, the no-observed-adverse-effect level（NOAEL） in juvenile rats was 22.2 g crude drug/kg, amount to 40 times the recommended dose（0.56 g crude drug/kg） for children aged 5-14, which suggested that the safety of long-term clinical use is fine.

关 键 词：参苓健脾胃颗粒 幼龄大鼠 毒性研究 

分 类 号：R962.2[医药卫生—药理学]