益智清心方单次给药毒性试验研究  

Single Dose Toxicity of Yizhi Qingxin Formula in Mice

作　　者：谭丽博 吴素素 魏微 曹宇[3] 马丽娜[3] 裴卉[3] 李浩 TAN Libo;WU Susu;WEI Wei;CAO Yu;MA Lina;PEI Hui;LI Hao(Beijing University of Chinese Medicine,Beijing 100029,China;Wang Jing Hospital of China Academy of Chinese Medical Sciences,Beijing 100102,China;Xiyuan Hospital of China Academy of Chinese Medical Sciences,Beijing 100091,China)

机构地区：[1]北京中医药大学,北京100029 [2]中国中医科学院望京医院,北京100102 [3]中国中医科学院西苑医院,北京100091

出　　处：《世界中医药》2024年第16期2399-2403,共5页World Chinese Medicine

基　　金：国家重点研发计划“中医药现代化”重点专项(2022YFC3501400)——基于“虚损瘀毒”病机基础的阿尔茨海默病中医诊疗规律系统化研究;国家自然科学基金青年科学基金项目(82104675)——参麻益智方干预小胶质细胞与血脑屏障互作治疗血管性痴呆的机制研究;中国中医科学院科技创新工程项目(CI2021A04618)——益智清心方干预衰老小胶质细胞治疗AD的作用机制研究;“优势病种-医院制剂-新药”研发专项(ZZ15-XY-PT-02)——治疗阿尔茨海默病的中药复方新药—益智清心颗粒的研究与开发;中国中医科学院科技创新工程(CI2021A01401)——老年期痴呆的创新中药与关键技术研究。

摘　　要：目的:观察24 h内益智清心方经口灌胃后的急性毒性反应和死亡情况,评价益智清心方的安全性,为进一步的重复给药毒性试验以及临床用药提供参考。方法:选取24~33 g ICR小鼠,雌雄各半,随机分为益智清心方组和空白对照组,采用最大给药量法,以最大灌胃体积40 mL/kg计,分别给予等体积的益智清心方药液和纯水,2次/d,给药期间定期监测小鼠一般状况和体质量,14 d后,收集血、尿样本,并进行大体解剖,评价益智清心方对脏器系数、血常规、尿常规等安全性指标的影响。结果:ICR小鼠按40 mL/kg经口灌胃给予最大可配制浓度为0.36 g干浸膏/mL的益智清心方药液,当日2次,累积剂量为98.6 g生药/kg体质量,约相当于成人临床拟用剂量的298倍(按公斤体质量计算)和38倍(按体表面积计算)。各组小鼠均未发现毒性相关的症状和死亡,益智清心方组小鼠在体质量、脏器系数、血常规、尿常规指标方面与对照组小鼠比较差异均无统计学意义(均P>0.05)。结论:本试验条件下,益智清心方的单次给药毒性试验中未见明显的急性毒性反应及死亡,提示其最大耐受量(MTD)>98.6 g生药/kg体质量。Objective:To evaluate the safety of Yizhi Qingxin Formula(YQF)by investigating the acute toxicity and death within 24 h after oral gavage of YQF,so as to provide reference for further study on repeated dose toxicity and clinical medication in practice.Methods:ICR mice(24 to 33 g),including equal numbers of male and female mice,were randomly divided into the YQF group and the blank control group.With the maximum dose method,an equal volume of YQF solution and pure water were given by oral gavage twice a day,based on the maximum gavage volume of 40 mL/kg.The general condition and body weight of the mice were monitored regularly during the oral administration period.After 14 days,blood and urine samples were collected,and gross anatomy was conducted to evaluate the effects of YQF on organ coefficient and routine blood and urine test results.Results:The ICR mice were orally administered by 40 mL/kg twice a day with YQF at a maximum concentration of 0.36 g dry extract/mL.The cumulative dose was 98.6 g crude drug/kg body weight,which was about 298 times(calculated by body weight in kilogram)and 38 times(calculated by body surface area)the proposed dose in adults.No toxicity-related symptoms and death of mice were observed in both groups.There was no statistical significance in body weight,organ coefficient,and routine blood and urine test results between the YQF group and the control group(P>0.05).Conclusion:Under the conditions of this study,no significant acute toxicity and death were observed in the experiment on the single dose acute oral toxicity of YQF in mice,showing its maximum tolerated dose was greater than 98.6 g crude drug/kg body weight.

关 键 词：临床前研究 单次给药毒性 小鼠 阿尔茨海默病 益智清心方 安全性 体质量 脏器系数 

分 类 号：R289[医药卫生—方剂学]