黄杨宁滴丸对大鼠反复灌胃给药8周的毒性试验研究

Toxicity of Huangyangning Dropping Pills on Rats after Repeated Gastric Administration for 8 Weeks

摘要: 目的：观察连续给予供试品后由于积蓄而对机体产生的毒性反应及其严重程度，提供毒性反应的器官及其损害的可逆性，确定无毒反应剂量，为拟定人用安全剂量提供参考。方法：采用SPF级Wistar大鼠对黄扬宁滴丸反复灌胃给药8周进行毒性试验。试验中分为高剂量组(给药剂量为20 mg/kg.BW按生药计，下同)，中剂量组(给药剂量为10 mg/kg.BW)、低剂量组(给药剂量为5 mg/kg.BW)和溶媒对照组(给予0.5% CMC-Na 10 mg/kg)，另设片剂对照组(给药剂量为10 mg/kg.BW)，连续给药8周后停药再继续观察二周。三个剂量组及片剂组分别相当临床用量的200、100、50、100倍。结果：各剂量组及黄杨宁片剂组和溶媒对照组在给药期间，其试验大鼠行为、活动、被毛、粪便等未见异常，体重及食量与对照组比较无显著差异(P > 0.05)，对血液学、血液生化学各指标检测，其测定值均在正常范围内。尸解后各重要脏器未见异常与肉眼可见病变。经病理组织学检查，高剂量组与对照组的各重要脏器无明显病变。停药二周后检测上述指标亦无异常。结论：黄杨宁滴丸对Wistar大鼠给药剂量20 mg/kg以下为安全剂量。

Abstract: Objective: To observe the toxicity and severity of the body caused by the accumulation of the test products, to provide the reversibility of the organs and damage of the toxic reaction, and to deter-mine the non-toxic dose, so as to provide reference for the formulation of safe dose for human use. Methods: The toxicity of Huangyangning Dropping Pills was tested in SPF Wistar rats by repeated intragastric administration for 8 weeks. The experiment was divided into high dose group (dosage is 20 mg/kg.BW according to the crude drug, the same below), medium dose group (dosage is 10 mg/kg.BW), low dose group (dosage is 5 mg/kg.BW) and solvent control group (dosage is 0.5% CMC-Na 10 mg/kg), and another tablet control group (dosage is 10 mg/kg.BW) was set up. After 8 weeks of continuous administration, the drug was discontinued and observed for another two weeks. The three dosage groups and tablet groups were 200, 100, 50 and 100 times of clinical dos-age respectively. Results: During the administration of Huangyangning tablet and solvent control group, there was no abnormal behavior, activity, coat, feces, weight and food intake in the experimental rats. There was no significant difference between the two groups (P > 0.05). The blood and blood biochemical indexes were tested, and the measured values were within the normal range. No abnormalities and naked eye lesions were found in the important organs after autopsy. Histopathological examination showed that there were no significant pathological changes in the important organs of the high dose group and the control group. There was no abnormality in the above indexes after two weeks of withdrawal. Conclusion: The safe dose of Huangyangning Dropping Pills for Wistar rats is below 20 mg/kg.