糖止丸的急性与亚急性毒性试验研究

Study on the Experiment of Acute and Subacute-toxicity of Tangzhi Pill

关键词:  糖止丸  急性毒性  亚急性毒性

Key words:  Tangzhi pill  acute toxicity  subacute toxicity

摘要:

目的 通过糖止丸的急性毒性、最大耐受量以及亚急性毒性试验，为临床安全用药提供依据。方法 急性毒性试验中设定3个剂量组，首次给药1次，连续观察7 d，记录糖止丸对小鼠体质量及进食量的影响；最大耐受量试验中将糖止丸按照最大溶解度配置成225 mg·mL^-1溶液，按小鼠最大给药体积40 mL·kg^-1灌胃给药，观察和记录中毒症状及死亡情况；亚急性毒性试验中将糖止丸分别按2.25，1.50，1.00 g·kg^-1配置成高、中、低3个剂量组溶液，10 mL·kg^-1灌胃，观察大鼠的亚急性毒性反应。结果 糖止丸急性毒性试验单次给药后观察7 d未见小鼠死亡，无法测出其LD₅₀。按照毒理学评价标准，LD₅₀>1 g·kg^-1属无毒性物质，最大耐受量试验中给药剂量增加到9 g·kg^-1仍未出现毒性，表明糖止丸对小鼠安全无毒。亚急性毒性试验，在高、中、低3个剂量连续用药30 d后，大鼠体征和各生理指标与空白对照组比较差异无统计学意义。结论 糖止丸安全性良好，可进一步用于治疗糖尿病的新药开发。

Abstract:

OBJECTIVE To provide evidence for the safety of clinical medication through the test on the acute toxicity, maximum tolerance and subacute toxicity of Tangzhi pill. METHODS In the acute toxicity experiment, three dose groups were set up, once for the first administration, the effects of Tangzhi pill on body weight and food intake of mice were observed continuously for 7 d. In the maximum tolerance test of mice, Tangzhi pill was prepared at a concentration of 225 mg·mL^-1 according to its maximum solubility. The drug was administered by gavage at 40 mL·kg^-1, toxic symptoms and deaths were observed and recorded after administration. In the subacute toxicity test, Tangzhi pill were prepared into high, medium and low dose group solutions at 2.25, 1.50 and 1.00 g·kg^-1, respectively, and 10 mL·kg^-1 were administered by gavage to observe the subacute toxicity reaction of rats. RESULTS No death of mice was observed in the acute toxicity test of Tangzhi pill for 7 d after administration for once, and LD₅₀ could not be measured. According to the toxicological evaluation standard, the substance with LD₅₀>1 g·kg^-1 had no toxicity. However, no toxicity was found when the dose was increased to 9 g·kg^-1 in maximum tolerance test, indicating that Tangzhi pill was safe and had no toxicity to mice. In the subacute toxicity experiment, there was no significant difference in signs and physiological indexes between the blank control group and the high, medium and low doses groups which were continuously administered for 30 d. CONCLUSION Tangzhi pill has good safety and can be further prepared into the preparation for the development of new drugs for the treatment of diabetes.