Beagle犬静脉滴注疏血通注射液急性毒性和反复给药毒性试验研究

Experimental study on acute and repeated dose toxicity of Shuxuetong Injection

目的观察Beagle犬静脉注射疏血通注射液的急性毒性和反复给药毒性,指导疏血通注射液临床安全合理用药。方法急性毒性试验采用最大给药剂量法,给药剂量为3.83g/kg,观察药后犬出现的毒性反应。反复给药毒性试验设0.75、0.15、0.03g/kg(相当于临床人用量的100、20、4倍)3个剂量组及生理盐水对照组,给药90d,停药后恢复期观察4周。检测指标包括动物一般状况、血液学和凝血、血清生化、尿检查及病理组织学等内容。结果急性毒性实验药后部分动物观察到了一过性的呼吸急促、肌颤及呕吐。疏血通注射液给药90d0.75g/kg组偶见咳嗽、呕吐、流涎,给药45d时各给药组的RBC、HGB略低于对照组,给药结束和恢复期结束时均未见异常,给药45d时0.75g/kg组的GLU绝对值略有增高,给药结束时未见正常。给药结束时对照组和高剂量组均可见给药部位血管刺激性病变,各组别其他脏器组织病理学检查未见明显异常。结论 Beagle犬静脉滴注疏血通注射液急性毒性的最大耐受剂量大于3.83g/kg;90d连续给药,其无毒作用剂量为0.15g/kg。结果提示在临床长期反复用药过程中注意患者血象的监测与血管的保护。

【Objective】To observe the acute and repeated dose toxicity of Shuxuetong Injection.【Methods】 The acute toxicity study was conducted with the maximum tolerance dose method by intravenous drip dose of 3.83 g·kg-1.For the repeated dose toxicity study,Shuxuetong Injection was administered via intravenous drip,at doses of 0.03,0.15,0.75 g·kg-1 for 3 consecutive months.Evaluation parameters included daily clinical signs,periodic hematology,clinical chemistry,and urinalysis and histopathology examination.【Results】 In acute toxicity study,transient shortness of breath,muscle trembling,vomiting° were observed during and after dosing.In repeated dose toxicity study,occasional transient cough,vomiting,salivation were observed at the dose 0.75 g·kg-1.Slightly decreased RBC,HGB and slightly increased GLU were observed at the dose of 0.75 g·kg-1 after 45 days of continuous administration,but all these parameters were noraml at end of 90 days of dosing and recovery period for 4 weeks.Vascular irritation was observed at the injection site at the end of administration for both control and high dose group.There were no toxicologically relevant finding at the end of recovery period.【Conclusions】The Maximum tolerated dose of Shuxuetong Injection is3.83 g·kg-1 and the no observed adverse effect level is 0.15 g·kg-1.Drug-related toxicity were limited to transient slightly decreased RBC,HGB and slightly increased GLU at the 0.75 g·kg-1 dose level.These data may provide useful information for clinical use.