壮药解毒抗白颗粒毒理学研究

Toxicologic Study on Zhuang Medicine of Jiedu Kangbai Granule

目的:观察动物灌胃给药(ig.)解毒抗白颗粒的急性毒性和长期毒性,确定无毒反应的剂量,以评估解毒抗白颗粒长期用药的安全性。方法:以解毒抗白颗粒浸膏给小鼠ig.给药;按原药材94.4g.kg-1、47.2g.kg-1、23.6g.kg-1(临床拟用日剂量的50倍、25倍、12.5倍)的剂量分别给大鼠连续灌服解毒抗白颗粒原药材浸膏91天,分阶段观察大鼠的生长发育,摄食量,血液学及血液生化学指征、脏器系数及组织病理学检查。结果:以解毒抗白颗粒浸膏给小鼠ig.给药,LD50为原药材96.473g/kg(95%可信限为84.79～108.31g.kg-1),LD5为原药材65.875g.kg-1,LD95为原药材141.28g.kg-1。长期毒性试验可出现血液网织红细胞(RET)明显增高、血清肌酸激酶(CK)活性明显降低、肝和肾脏器指数增大的现象;在94.4g.kg-1剂量组还出现体重增长缓慢、摄食量减少、血红蛋白(HGB)轻度降低;但这些改变均为可逆的,在停药2周后可恢复正常或有恢复正常的趋势。未观察到其它明显的慢性毒性反应和延缓毒性反应。结论:小鼠急性毒性和大鼠长期毒性试验结果提示,解毒抗白颗粒样品按临床拟定剂量、途径、疗程在临床上应用可能是安全的。

Objective： To observe the acute toxicity of Jiedu Kangbai Granule in rats and determine the safety dosage window.Therefore,we evaluated the safety of long-term prescription.Method： Given the extract of Jiedu Kangbai Granule to the mice,and the extract of crude drug in whole was given to rats for 91 days at a dosage of 94.4,47.2,23.6g/kg（as the 50,25 and 12.5 times of clinical use daily dose）.Moreover,observed the growth and development,food intake,the indication of hematology and blood biochemical analysis,organ coefficient and histopathology.Result： Given the extract of Jiedu Kangbai Granule to the mice,lethal dose50（LD50）was crude drug 96.473g/kg（The 95% confidence limits were 84.79～108.31g/kg）.lethal dose5（LD5）was crude drug 65.875g/kg and lethal dose95（LD5）was crude drug 141.28g/kg.The phenomena of granulophilocyte（RET）increasing、activity of creatine kinase（CK） in blood serum reduction obviously、liver and kidney＇s index number increscent had been found in longtermtoxicitytst in rats.Pondered growth slowly、food consumptionreduced、hemoglobin（HGB）slight fall were found in the dose groups of 94.4g/kg.The above phenomena reversible and almost disappeared after two weeks of stopping treatment,unobserved the other obvious chronic toxicity and delay toxicity reaction.Conclusion： The test results of acute toxicity in mice and long-term toxicity in rats prompting that the sample of Jiedu Kangbai Granule is safe in clinically by the protocol of dose、approach and the course of treatment.