| 摘要: |
| 目的：评价清热散结胶囊干浸膏重复给药4周对SD大鼠的长期毒性。方法：选取检疫合格的SD大鼠120只，按性别、体质量随机分为溶媒对照组及清热散结胶囊干浸膏低剂量（29.0g生药/kg）、中剂量（55.7g生药/kg）、高剂量（111.3 g生药/kg）组，每组各30只，按15 ml/kg经口灌胃给药，1次/d，连续给药4周，并经4周停药恢复，评价受试药物对大鼠体质量、平均摄食量、血液学、凝血、血生化、脏器系数、各阶段主要背景性病理改变及发生情况等指标的影响。结果：清热散结胶囊干浸膏对大鼠体质量、平均摄食量、血液学、凝血、血生化、脏器系数等指标均无明显影响（P>0.05），组织病理学检查未见与受试药物相关的病理改变。结论：清热散结胶囊干浸膏重复给药4周，无明显损害作用剂量（NOAEL）为111.3 g生药/kg（相当于60 kg成人临床拟用剂量的94倍，等效剂量的17倍），大鼠未见明显毒性反应，可能与处方中千里光的原药材控制以及产品的提取生产工艺有效控制了产品中吡咯里西啶生物碱类有毒成分的含量有关。研究结果显示，清热散结胶囊的NOAEL剂量与临床拟用量具有较大的间距，提示临床应用时安全范围大，临床使用安全性风险小。 |
| 关键词: 清热散结胶囊 千里光 重复给药 毒性实验 |
| DOI： |
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| Toxicity of the dry extract of Qingre Sanjie capsules：An experimental study |
| CHEN Qiongfang,LIN Xinwen,WANG Xiaoqing |
| (Hunan Province Drug Safety Evaluation and Research Center/Hunan Key Laboratory of Pharmacodynamics and Safety Evaluation of New Drugs，Changsha 410331，Hunan，China;Hunan Drug Inspection Center，Changsha 410001，Hunan，China) |
| Abstract: |
| Objective：To investigate the long-term toxicity of the dry extract of Qingre Sanjie capsules after 4 weeks of repeated administration in Sprague-Dawley (SD) rats.Methods：A total of 120 SD rats which passed quarantine inspection were selected，and according to sex and body weight，they were randomly divided into solvent control group，low-dose dry extract group (29.0 g crude drug/kg)，middle-dose dry extract group (55.7 g crude drug/kg)，and high-dose dry extract group (111.3 g crude drug/kg)，with 30 rats in each group.The rats were administered at a dose of 15 ml/kg by gavage，once a day for 4 consecutive weeks，followed by 4 weeks of drug withdrawal and recovery.The test drug was evaluated in terms of its influence on the indicators such as body weight，mean food intake，hematology，coagulation，blood biochemistry，organ coefficient，and background pathological changes in each stage.Results：The dry extract of Qingre Sanjie capsules showed no significant influence on the indicators of body weight，mean food intake，hematology，coagulation，blood biochemistry，and organ coefficient (P>0.05)，and histopathological examination showed no pathological changes associated with the test drug.Conclusion：The no-observed-adverse-effect-level (NOAEL) is 111.3 g crude drug/kg (which is 94 times of the intended dose for adults with a body weight of 60 kg in clinical practice and 17 times of the equivalent dose) for the dry extract of Qingre Sanjie capsules after 4 weeks of repeated administration.No obvious toxicity is observed in rats，which may be associated with the fact that the original medicinal material groundsel in the prescription is properly controlled and that the toxic components pyrrolizidine alkaloids are effectively controlled by the extraction and production processes of the product.Study results show a large gap between the NOAEL dose of Qingre Sanjie capsules and its intended dose in clinical practice，which indicates a large safety range and a low safety risk during clinical application. |
| Key words: Qingre Sanjie capsules groundsel repeated administration toxicity experiment |
