小儿复方鸡内金咀嚼片对幼龄大鼠28 d重复灌胃给药毒性研究

Toxicity of Child Compound Endothelium Corneum Chewable Tablets by Repeated Gavage for 28 d in Young Rats

目的为小儿复方鸡内金咀嚼片临床安全用药的剂量设计和临床毒副反应监测提供参考。方法取幼龄SD大鼠120只,随机分为溶剂对照组(A组,羧甲基纤维素钠),小儿复方鸡内金咀嚼片低、中、高剂量组(B1组、B2组、B3组,六神曲鸡内金混合粉以生药计0.375,1.125,3 g/kg,相当于临床拟用剂量的6倍、18倍、48倍),按体质量每100 g灌胃给药1 mL,连续4周,恢复期30 d,给药结束和恢复期结束时剖杀,进行一般生理指标观察、临床病理学检查、组织病理学检查、神经行为测试。结果与A组比较,给药结束时雌鼠B1组的平均红细胞血红蛋白浓度显著降低(P<0.05);雌鼠B2组、B3组的甘油三酯均显著降低(P<0.05),雌鼠B3组的氯离子浓度显著升高(P<0.05),雌鼠B1组的钙离子浓度显著降低(P<0.05),雄鼠B1组的乳酸脱氢酶水平显著升高(P<0.05),雄鼠B3组的总胆固醇显著降低(P<0.05),雄鼠B1组、B3组的钠离子浓度均显著升高(P<0.05),但上述指标改变均无毒理学意义。各组大鼠组织病理学检查均未见与给药相关的蓄积性或延迟性毒性病理改变。结论小儿复方鸡内金咀嚼片未见明显毒性反应剂量为3 g/kg,相当于临床拟用剂量的48倍。

Objective To provide a reference for the clinical safe dose design and clinical toxicity monitoring of Child Compound Endothelium Corneum Chewable Tablets(CCECCT).Methods A total of 120 young SD rats were selected and randomly divided into the solvent control group(group A,sodium carboxymethyl cellulose),the low-,medium-,and high-dose CCECCT groups(groups B1,B2,B3,Liushenqu Endothelium Corneum Mixed Powder with doses of 0.375,1.125,and 3 g/kg of raw materials respectively,equivalent to 6 times,18 times,and 48 times the clinical intended dose).The administration volume was 1 mL/100 g by intragastric administration for 4 weeks,and the recovery period was 30 d.At the end of the drug administration and recovery period,the autopsy was performed for general physiological indicators observation,clinical pathological examination,histopathological examination,and neurobehavioral testing.Results At the end of the drug administration,compared with those in group A,the mean hemoglobin concentration of female mice in group B1 significantly decreased(P<0.05);the triglycerides of female mice in groups B2 and B3 significantly decreased(P<0.05),the chloride ions concentration of female mice in group B3 significantly increased(P<0.05),the calcium ion of female mice in group B1 significantly decreased(P<0.05),the lactate dehydrogenase of male mice in group B1 significantly increased(P<0.05),the total cholesterol of male mice in group B3 significantly decreased(P<0.05),while the sodium ion concentration of male mice in groups B1 and B3 significantly increased(P<0.05).However,the changes in the above indicators had no toxicological significance,and no accumulative or delayed toxic pathological changes related to drug administration were observed in the tissue pathology of rats in each group.Conclusion The no observed adverse effect level(NOAEL)for CCECCT is 3 g/kg,which is 48 times the clinical intended dose.