复方止痢中药制剂对大鼠长期毒性研究
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摘要
为评价复方止痢中药制剂长期用药的安全性,利用其对大鼠进行长期毒性试验,将160只SD大鼠随机分为低、中、高剂量组(分别为6.66、22.20、66.60 g/kg)和对照组(生理盐水20. 00 m L/kg) 4组,每组40只,雌雄各半。保证每天给药1次,每周给药6 d,连续给药6个月。记录大鼠的临床症状和体质量,并分别于给药第3个月和第6个月进行血液学、血清生化指标检测,并进行系统尸检以及脏器系数、组织病理学检查。结果表明,灌胃复方止痢中药制剂后,大鼠均存活,饮水、采食等行为活动表现正常,体质量明显增加;各剂量组血液学及血清生化指标与对照组相比无显著性差异,且停药2周后各指标也均无显著性差异;剖检观测各脏器组织位置、质量和脏器系数均正常,部分脏器质量有所增加,与对照组相比无显著性差异;组织病理学检查结果表明,高剂量组和对照组大鼠未见明显与给药相关的异常病理和毒性改变,恢复期停药后未见延迟性毒性。因此,长期服用复方止痢中药制剂对大鼠未见明确的毒性反应,停药后亦无延迟性毒性反应,说明复方止痢中药制剂具有良好的临床安全性。
In order to evaluate the safety of long-term treatment of compound Chinese medicine preparations in rats,long-term toxicity test was used. 160 SD rats were randomly divided into 4 group:low,medium and high dose groups( 6. 66,22. 20,66. 60 g/kg) and blank control group( physiological saline 20. 00 m L/kg),each group included 40 rats( male ∶ female = 1 ∶ 1). Rats were administered compound Chinese medicine preparations once a day for 6 days per week for 6 months. The clinical symptoms and body weight of the rats were recorded. At the 3rd and 6th month,each group was tested for the haematological indexes,biochemical indexes,organ coefficients and histopathological examination. The results showed that the rats survived after the administration of the medicine,and the activities of drinking water and feeding were normal and the body weight increased significantly. The haematological and biochemical indexes of each dose group were not significantly different from the control group,and the same as 2-week restoration. The position,weight and organ coefficient of each organ were normal and theweight of some organs increased. There was no significant difference compared with the control group. The pathological results showed that there were no obviously pathological and toxic changes of drug administration of rats in the compound Chinese medicine preparations high-dose group and the control group,and no delayed toxicity after the withdrawal period. Therefore,the long-term use of compound Chinese medicine preparations has no toxicity in rats,and there is no delayed toxicity after stopping the medicine. The test showed that compound Chinese medicine preparations are safe in clinical practice.
In order to evaluate the safety of long-term treatment of compound Chinese medicine preparations in rats,long-term toxicity test was used. 160 SD rats were randomly divided into 4 group:low,medium and high dose groups( 6. 66,22. 20,66. 60 g/kg) and blank control group( physiological saline 20. 00 m L/kg),each group included 40 rats( male ∶ female = 1 ∶ 1). Rats were administered compound Chinese medicine preparations once a day for 6 days per week for 6 months. The clinical symptoms and body weight of the rats were recorded. At the 3rd and 6th month,each group was tested for the haematological indexes,biochemical indexes,organ coefficients and histopathological examination. The results showed that the rats survived after the administration of the medicine,and the activities of drinking water and feeding were normal and the body weight increased significantly. The haematological and biochemical indexes of each dose group were not significantly different from the control group,and the same as 2-week restoration. The position,weight and organ coefficient of each organ were normal and theweight of some organs increased. There was no significant difference compared with the control group. The pathological results showed that there were no obviously pathological and toxic changes of drug administration of rats in the compound Chinese medicine preparations high-dose group and the control group,and no delayed toxicity after the withdrawal period. Therefore,the long-term use of compound Chinese medicine preparations has no toxicity in rats,and there is no delayed toxicity after stopping the medicine. The test showed that compound Chinese medicine preparations are safe in clinical practice.
引文
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[2]王建华,张永祥.中药药理与临床研究进展[M].北京:军事医学科学出版社,2006.
[3]冯将,魏玉好,余波,等.中药复方及拆方的抗炎、镇痛、抑菌活性评价[J].中国兽药杂志,2017,51(12):30-35.
[4]许迪,孔利佳,杜佐华,等.大鼠长期毒性试验质量控制探讨[J].中国比较医学杂志,2010,20(1):61-63.
[5]张海晶,孙桂波,陈荣昌,等.安神补脑液对大鼠长期毒性的观察[J].中国实验动物学报,2015,23(2):147-152.
[6]白文霞,吉兰姣,梅胜尧,等.复方葛根素冻干粉针对大鼠的长期毒性试验[J].毒理学杂志,2010,24(3):249-251.
[7]邱麒,张睿卓,邱麟,等.养心草安神颗粒对大鼠长期毒性试验研究[J].辽宁中医药大学学报,2017,19(9):31-35.
[8]范菲,郭甜甜,李静静,等.呋喃妥因及其有关物质对大鼠的长期毒性研究[J].药物分析杂志,2013,33(1):7-11.
[9]国家食品药品监督管理局.化学药物长期毒性试验技术指导原则[M].北京:中国医药科技出版社,2005.
[10]国家食品药品监督管理局.药物非临床质量管理规范[M].北京:中国医药科技出版社,2003.
[11]国家食品药品监督管理局.中药、天然产物急性毒理研究技术指导原则[M].北京:中国医药科技出版社,2005.
[12]唐远江,尚以顺,周思旋,等.多叶勾儿茶主要成分提取及抗氧化活性初探[J].贵州农业科学,2017,45(11):121-125.
[13]刘佳龙.预防奶牛乳房炎地榆膜剂的研制及其家兔模型效果研究[D].保定:河北农业大学,2014.
[14]来伟旗,朱梁枫,陈建国,等.乌药的毒性研究[J].职业与健康,2003,19(12):78-80.
[15]潘洪平,危华玲,陈英,等.复方黄酮胶囊的急性毒性作用研究[J].时珍国医国药,2007,18(10):2378.
[16]陈学兴.萹蓄颗粒剂工艺及药理研究[D].郑州:河南中医学院,2008.
[17]刘霆,陈玉祥,赵颜忠,等.银杏内酯软胶囊毒理学研究[J].中国现代医学杂志,2003,13(6):24-27.
[18]姜玲玲,陈鸿宇,史开志,等.一种新兽用止泻中药复方制剂对大鼠的亚慢性毒性研究[J].江苏农业科学,2017,45(16):148-151,160.