得力康注射液安全性药理学和急性毒性研究

Studies on Safety and Acute Toxicity of Delikang Injection

目的观察慢速iv得力康注射液对大鼠循环、呼吸系统和小鼠中枢神经系统的影响;观察静滴得力康注射液对Beagle犬的急性毒性。方法大、小鼠实验均分低、中、高剂量及空白对照共4个组,对大鼠血压、ECG、呼吸频率及节律,小鼠自发活动和爬杆能力进行观察。用近似致死剂量法(ALD)观察得力康注射液对6条Beagle犬的急性毒性,观察其一般情况、心电图、血液学、血液生化、尿液检查。结果慢速iv得力康注射液1.00～4.00g/kg对大鼠循环、呼吸系统无明显影响,2.00～8.00g/kg对小鼠中枢神经系统也无明显影响。犬静滴得力康注射液8.00～12.00g/kg时产生中重度中毒症状,主要表现有给药期间中枢先兴奋后抑制,全身皮肤潮红、眼睑肿胀明显,局部肌肉抽搐,恶心、呕吐。剂量为12.00g/kg时,犬第1天的ALT、AST、ALP、Tbill、Ca2+、K+升高,ECGT波电压升高,第7天基本恢复正常。结论得力康注射液静滴Beagle犬,当剂量>8.00g/kg时,对中枢神经系统、循环及消化系统有明显毒副作用,毒副作用均是可逆的。得力康注射液静滴Beagle犬安全剂量为3.56g/kg,ALD>12.00g/kg。

Objective To study the effects of Delikang injection (DI) on circulatory and respiratory system in rats and on central nervous system (CNS) in mice and to study the acute toxicity of Delikang injection in Beagle dogs.Methods Both rats and mice were randomized into low dosage group,moderate dosage group,high dosage group and control group to observe the safety of DI. Blood pressure,electrocardiogram (ECG),respiratory rate and rhythm in rats as well as spontaneous activity and pull-down ability in mice were observed to evaluate the safety. The acute toxicity of DI was studied in 6 Beagle dogs with approximate lethal dose method (ALD). General status,ECG and parameters of hematology,blood biochemistry and urine were measured to evaluate the toxicity.Results Slow injection of DI at the dose of 1.00～4.00 g/kg had no obvious effects on rats circulatory and respiratory system;DI at the dose of 2.00～8.00 g/kg had no obvious effects on CNS in mice.Intravenous drip of DI at the dose of 8.00～12.00 g/kg showed moderate to severe toxicity in dogs:the CNS first excited then suppressed,flushed skin,obviously swelling of eyelids,nausea,vomiting and local muscular spasms.On the first day of medication of 12.00 g/kg DI,serum levels of ALT,AST,ALP,Tbill,Ca2+and K+and T wave of ECG were found above normal level;the above indexes recover to normal on the seventh day of medication.Conclusion DI has obvious toxic effects on CNS and circulatory and digestive system when intravenous drip dose is above 8.00 g/kg. All these toxic effects are reversible.The intravenous drip safety dosage of DI in Beagle dogs is 3.56 g/kg. ALD>12.00 g/kg.