含何首乌中药制剂首荟通便胶囊大鼠13周重复给药毒性研究  

The repeated toxicity of Shouhui Tongbian capsules prepared from polygoni multiflori radix for 13 weeks in rats

作　　者：崔丽娟 李斌 岳玲 王梦琳 关永霞 陈雪 姚景春 CUI Li-juan;LI Bin;YUE Ling;WANG Meng-lin;GUAN Yong-xia;CHEN Xue;YAO Jing-chun(Lunan Pharmaceutical Group Co.,Ltd.,State Key Laboratory of Integration and Innovation of Classic Formula and Modern Chinese Medicine,Linyi,Shandong 273400,China;Lunan Pharmaceutical Group Co.,Ltd New Drug Safety Assessment Center,Linyi,Shandong 273400,China;West China-Frontier Pharma Tech,Chengdu,Sichuan 610041,China)

机构地区：[1]鲁南制药集团股份有限公司,经方与现代中药融合创新全国重点实验室,山东临沂273400 [2]鲁南制药集团股份有限公司新药安评中心,山东临沂273400 [3]成都华西海圻医药科技有限公司,四川成都610041

出　　处：《毒理学杂志》2023年第4期312-321,共10页Journal of Toxicology

基　　金：山东省科学技术厅重点研发计划“重大科技创新工程”(2021CXGC010508)。

摘　　要：目的评价含何首乌的已上市中药制剂首荟通便胶囊的安全性,为临床安全用药提供参考。方法大鼠分别灌胃给予低、中、高剂量(0.75、1.5和3 g/kg)的首荟通便胶囊,每日1次,连续13周,对照组给予相同体积的灭菌注射用水。试验期间观察动物的一般状况,对体重、摄食量、血液学、血生化、眼科检查、尿液分析、脏器重量及系数、骨髓涂片、大体解剖及组织病理学等项目进行检查。结果首荟通便胶囊高剂量组所有大鼠给药1周时相继出现轻度唾液分泌增多,停药后体征消失;除此以外,各组各指标与对照组比较,差异均无统计学意义(P>0.05)。结论SD大鼠每日1次、连续13周经口灌胃给予0.75、1.5和3 g/kg首荟通便胶囊,无毒性反应剂量(NOAEL)为3 g/kg(8 g生药/kg,约为临床剂量的100倍),此剂量下SD大鼠口服首荟通便胶囊13周没有发现潜在的肝毒性、结肠黑便毒性及其他毒性反应。Objective To evaluate the safety of Shouhui Tongbian capsule,a listed traditional Chinese medicine preparation containing Polygonum multiflorum,so as to provide reference for clinical safe drug use.Methods The rats were orally given Shouhui Tongbian capsule of low,middle and high doses(0.75,1.5 and 3 g/kg)once a day for 13 weeks,while the control group was given the same volume of sterilized water for injection.The general condition of the animals was observed during the experiment,and the items such as body weight,food intake,hematology,blood biochemistry,ophthalmology,urine analysis,organ weight and coefficient,bone marrow smear,gross anatomy and histopathology were examined.Results One week after administration,all the rats in the high⁃dose Shouhui Tongbian capsule group showed a slight increase in saliva secretion,and the symptoms disappeared after drug withdrawal.In addition,there were no significant abnormal changes in the indexes of each group compared with the control group(P>0.05).Conclusion SD rats were given 0.75,1.5 and 3 g/kg Shouhui Tongbian capsule by oral gavage once a day for 13 consecutive weeks.The no⁃observed-adverse⁃effect level(NOAEL)was 3 g/kg.At this dose,no potential liver and colon black stool toxicity and other toxic reactions were found in SD rats after oral administration of Shouhui Tongbian capsule for 13 weeks.

关 键 词：首荟通便胶囊 何首乌 肝毒性 大鼠 毒性研究 

分 类 号：R992[医药卫生—毒理学] R114[医药卫生—药学]