参知健脑胶囊对Beagle犬的急性毒理研究

目的：观察Beagle犬灌胃给予参知健脑胶囊后,所出现的急性毒性反应情况,为临床前反复给药的毒性研究和临床安全用药提供参考。方法：试验用Beagle犬6只,随机分为3组,分别为低、中、高剂量组,每组雌雄各1只,经口灌胃给药。实验设计的给药剂量分别为1 000、2 000和5 000 mg/kg,由于中、高剂量组动物药后呕吐,中剂量组2只动物的实际给药剂量均约为2 000 mg/kg,高剂量组2只动物的实际给药剂量为2 209和3 092 mg/kg,药物浓度为100 mg/ml。给药后进行了14 d的临床观察,期间进行了体重、体温、心电图、血细胞计数、凝血功能、血液生化和眼科检查指标检测。观察期结束后,将所有动物安乐处死,进行解剖观察。结果：试验期间,没有发现动物死亡或濒死。低剂量组动物未见临床异常反应,中、高剂量组4只动物临床反应为药后一过性呕吐和稀便,药后次日至观察期结束未见异常反应。6只动物的体重、体温、心电图、血细胞计数、凝血功能、血液生化、眼科检查等均未见有与药物相关的规律性改变。大体解剖未见组织、脏器的病理改变。结论：在本试验条件下,参知健脑胶囊单次灌胃给予Beagle犬,安全剂量为1 000 mg/kg,最大耐受量（MTD）大于3 000 mg/kg。

Acute toxicological study of Shenzhi Jiannao Capsule on Beagle Dogs

Objective: To observe the acute toxicity reaction of Beagle dogs after poured Shenzhi Jiannao Capsule into their stomachs to provide reference for toxicity study of dosing repeatedly before clinical research and safe use of drugs in clinical research.Methods: Six Beagle dogs were randomly divided into three groups,including QDTMTL,QDTMTM and QDTMTH with one male and one female in every group.The drug administration was oral gavage.The dosages of original design were designed as 1 000,2 000 and 5 000 mg/kg,but due to vomitting of QDTMTM and QDTMTH after oral gavage,the actual dosage of QDTMTM was both approximately 2 000mg/kg,and the actual dosage of QDTMTH were approximately 2 209 and 3 092 mg/kg.There was a 14-day clinical observation after dose,and among that period,the animals′weight,temperature,ECG,blood cell count,blood coagulation,blood biochemistry,eye examination were observed.Afer clinical observation,all the dogs were euthanized,and observed for the gross anatomy.Results: In the period of test,there wasn’t animal death or articulo mortis;there wasn’t abnormal clinical reaction found in QDTMTL,but transient vomiting and loose stools after oral gavage were observed in QDTMTM and QDTMTH.However,there wasn’t abnormal clinical reaction from morrow to end of the experiment.There wasn’t any regularly change of drug-related in the results of all the animals′weight,temperature,ECG,blood cell count,blood coagulation,blood biochemistry,eye examination.There was no change abnormal in the gross anatomy of animals′tissue and viscera.Conclusion: In this experiment condition,the safe dose of single gavage of Shenzhi Jiannao Capsule for Beagle dogs is 1 000 mg/kg,and MTD is greater than 3 000 mg/kg.