复方天门冬多糖注射液的毒理学试验及安全性评价

Toxicology test and safety evaluation of compound Asparagus cochinchinensis polysaccharide injection

【目的】验证复方天门冬多糖注射液的安全性,为临床用药提供参考依据。【方法】利用复方天门冬多糖注射液分别进行急性毒性试验、局部刺激性试验和亚慢性毒性试验,确定临床给药的最佳途径和最有效剂量。【结果】急性毒性试验结果表明,复方天门冬多糖注射液属于实际无毒。局部刺激试验结果表明,该复方制剂适合于黏膜给药和肌肉注射用药。亚慢性毒性结果表明,在腹腔注射剂量<1.60g/kg时,小鼠的谷丙转氨酶(ALT)、谷草转氨酶(AST)活性及肌酐、尿素氮水平与空白对照组(注射生理盐水)相比无显著差异(P>0.05),肝脏、脾脏和肾脏组织形态学也无可见病理变化。复方天门冬多糖注射液剂量在2.50～5.00g/kg时,ALT、AST活性及肌酐、尿素氮水平显著或极显著升高(P<0.05或P<0.01),超出正常值范围。对肝脏、肾脏和脾脏进行病理学观察,也发现肝索排列紊乱,部分肝细胞核破碎、溶解,结缔组织和内皮细胞增生。【结论】复方天门冬多糖注射液安全无毒,既可黏膜给药又可肌肉注射用药,但用药剂量应小于1.60g/kg。

Objective The safety of the compound Asparagus cochinchinensis polysaccharide （ACP） injection was veri- fied to provide references for its clinical application. Method Using the compound ACP injection, the acute toxicity test, local irritation test and chronic toxicity test were conducted to determine its best pathway and dosage for medical purpose. Results The acute toxicity test indicated that the compound ACP had low toxicity. Local irritation experiments showed that the compound ACP injection was suitable for mucosal and intramuscular administration. The results of sub-chronic toxicity test showed that under 1.60 g/kg intraperitoneal injected dose, Alanine transaminase （ALT） activity, Aspartate Transaminase （AST） activity, creatinine and the level of urea nitrogen were not significantly different （P0.05） from that of the control group. There was no visible pathological changes on the liver, spleen and kidney histology. In the injection dose range of 2.50-5.00 g/kg, ALT activity, AST activity, creatinine and the level of urea nitrogen significantly or extremely significantly ascended （P 0.05 or P 0.01）, exceeding the normal value range. According to pathological observation, there existed disorganized hepatic cell cords in the liver, partially broken and dissolved liver cell nucleus, and endothelial cell proliferation. Conclusion The compound ACP injection was toxicity-free, and less than 1.6 g/kg dose could be used for mucosal and intramuscular administration.