翻白草胶囊的毒理安全性试验

Study on acute and chronic toxicities of Potentilla discolor Capsules

目的研究翻白草胶囊的急性毒性及长期毒性。方法采用最大耐受量法进行小鼠急性毒性试验,30 g/kg翻白草胶囊ig给予小鼠,间隔6 h给药2次,观察体质量、进食情况、外观情况、行为活动、是否出现死亡现象等,连续观察1周;将清洁级别的80只大鼠随机分为对照组和翻白草胶囊高、中、低剂量(4.8、2.4、1.2 g/kg)组,每天ig给药1次,每周给药6次,连续给药90 d,并停药观察15 d,观察大鼠外观体征、饮食、体质量等情况,并进行一般形态学、血液学、脏器形态学、血液生化学、组织病理学检测。结果急性毒性试验期间内无小鼠死亡现象,小鼠对药物的最大耐受量为30 g/kg,相当于人临床用药剂量的320倍。长期毒性试验结果表明,翻白草胶囊高剂量组在给药初期,部分动物出现精神萎靡、厌食、大便偶见溏稀化、口周出现青紫状斑点等现象,连续给药后可自行缓解;与对照组比较,翻白草胶囊组血液学、脏器形态学、血液生化学指标均未出现剂量相关性的显著变化,无明显药物毒性反应;给药90 d后,翻白草胶囊高剂量肺组织切片光镜下偶见局部出现点状炎症细胞,卵巢偶见炎症细胞并伴有脓细胞,停药15 d后症状消失。结论在本实验条件下,翻白草胶囊对受试动物无明显毒性反应,安全剂量范围大,在有效剂量下,长期用药安全。

Objective To investigate possible acute and chronic toxicities of Potentilla discolor Capsules（PDC） for clinical reference. Methods Maximal tolerated dose was established in mice for acute toxicity evaluation. PDC of 30 g/kg was ig given to mice 2 times at 6 h intervals. The body mass, eating condition, appearance, behavior, and death were observed for one week. In the chronic toxicological study, 80 rats were randomly divided into control group, PDC high, medium, and low dose groups, and given intragastrically for 6 times weekly for 90 d. The patients were then followed for 15 d for recovery without treatement. The signs, diet, body weight, and other signs of the rats were observed, and the morphology, hematology, organ morphology, blood biochemistry, and histopathology were examined. Results No death was observed in mouse acute toxicity test. The maximal tolerated dose was 30 g/kg, quivalent to 320 times of the clinically recommended dose for human. The long-term toxicity test results showed that parts of mice in the PDC high dose groupHad the abnormal phenomena of listlessness, anorexia, occasionally loose stool, perioral bruising spots and other phenomena in the initial administration, which were relieved after continuous administration. Compared with control group, there were no significant changes in the hematology, visceral morphology, and blood biochemical indexes in PDC group, and there was no significant drug toxicity. After continuous administration for 90 d, lung tissue sections of PDC high dose group showed occasional punctiform local inflammatory cells under the light microscope, the inflammatory cells combined with pus cells were seen in ovarian pairs, the symptoms were disappeared 15 d after withdrawal. Conclusion Under the conditions of this experiment, the capsule has no obvious toxic reaction to the tested animals with large safe dose range and long-term medication safety in effective dosage.