蒙成药孟根乌苏-18 味丸的急性毒性和长期毒性研究

目的：观察孟根乌苏-18味丸的急性毒性和长期毒性反应，为临床安全用药提供参考依据。方法：以最大允许浓度（0.4 g·mL-1）在6 h内灌胃给予小鼠孟根乌苏-18味丸混悬液两次（0.2 mL/10 g），观察14天，考察其急性毒性反应；大鼠每天分别灌胃给予孟根乌苏-18味丸高、中、低剂量（3.67 g·kg-1、1.84 g·kg-1、0.92 g·kg-1）1次，连续给药180天，停药观察60天。结果：孟根乌苏-18味丸最大耐受量>16 g·kg-1（相当临床用量的436.36倍）。给药180天后，与对照组相比，孟根乌苏-18味丸高剂量组ALB、UREA、AST、TBIL、CHOL有显著性或非常显著性差异（P<0.05或P<0.01），中剂量ALB、UREA有显著性差异（P<0.05），低剂量组无显著性差异；高剂量组出现蛋白管型伴近曲小管上皮细胞不同程度变性坏死。停药60天后，与对照组比较，各组动物的一般状况、体质量、血液学指标、血清生化学指标、脏器系数等无显著性差异，高剂量组肾脏器质性病变出现了恢复趋势。结论：孟根乌苏-18味丸大鼠灌胃给药的基本安全剂量为0.92 g·kg-1（相当于临床拟用剂量的25倍）。

Experimental Research on Acute Toxicity and Long-term Toxicity of Mongolian Patent Drug Meng-Gen-Wu-Su-18 Pills

This study was aimed to observe the acute toxicity and long-term toxicity of Meng-Gen-Wu-Su-18 (MGWS-18) Pills, in order to provide references for safety application of this medicine in the clinical practice. MGWS-18 Pills suspension was intragastric administered to mice twice (0.2 mL/10 g) in 6 hours with maximal concentration (0.4 g·mL-1). And the acute toxicity reaction was observed for 14 days. The dose of maximum, middle and minimum (3.67 g·kg-1, 1.84 g·kg-1, 0.92 g·kg-1) of MGWS-18 Pills were intragastric administered continuously to rats once a day for 180 days. The rats were observed 60 days after drug withdrawal. The results showed that the maximal tolerated dose (MTD) of MGWS-18 Pills was bigger than the dose of 16 g·kg-1 (which was equivalent to 436.36 times in clinical doses). There were significant differences on ALB, UREA, AST, TBIL, and CHOL between the control group and the maximum dose group of MGWS-18 Pills (P < 0.05, or P < 0.01) after 180 days of medication. There were significant differences on ALB and UREA between the control group and the middle dose group (P < 0.05). There was no significant difference between the control group and the minimum dose group. Protein cast and degeneration necrosis at different levels of the epithelial cells of the proximal tubules were appeared in the maximum dose group after medication for 180 days. After 60 days of drug withdrawal, there were no significant differences on the general condition, body weight, hematological indexes, serum biochemical indexes, organ coefficient and etc. between the control group and each animal group. There was recovery tendency on the kidney damage of the maximum dose group. It was concluded that the basic safety intragastric administration dosage of MGWS-18 Pills in rats was 0.92 g·kg-1 (which was equivalent to 25 times in clinical doses).