达立通提取液颗粒、达立通提取液及回收液颗粒灌胃给药安全性评价

摘要/Abstract

摘要： 目的：观察达立通提取液颗粒、达立通提取液及回收液颗粒灌胃给药长期毒性反应，比较二者的毒性情况，为临床安全用药及资源再利用提供参考。方法：将SD大鼠分为7组：阴性对照组，达立通提取液颗粒35.01、17.51、8.75 g·kg-1剂量组和达立通提取液及回收液颗粒35.01、17.51、8.75 g·kg-1剂量组。连续灌胃给药3个月，恢复期观察1个月，观察各组大鼠的生长、发育、血液学、血清生化学及病理组织变化，比较二者的毒性反应情况。结果：两种颗粒剂雄性大鼠体重高于阴性对照组，雌性大鼠体重低于阴性对照组，一些时间点体重与对照组差异均有统计学意义（P<0.05）；与对照组相比，随给药时间的延长，给药组大鼠摄食量呈减少趋势，恢复期呈增加趋势；给药末期两种颗粒雄性大鼠高剂量组中性粒细胞百分比（Neu%）减少、淋巴细胞百分比（Lym%）增加(P<0.05)，雌性大鼠高剂量组大鼠血小板（PLT）计数均减少（P<0.05），恢复期恢复正常水平；给药末期雄性大鼠达立通提取液颗粒高剂量组丙氨酸转氨酶（ALT）和各剂量组天冬氨酸转氨酶（AST）均减少，达立通提取液及回收液颗粒低中剂量组ALT和AST均减少（P<0.05），恢复期无异常；达立通其提取液及回收液颗粒低中剂量组甘油三酯（TG）增加（P<0.05）；给药末期雄性大鼠中高剂量组、雌性大鼠高剂量组肝系数均增加（P<0.05），恢复期无异常；给药后组织病理学检查显示主要病变为肝点状坏死，但与对照组比较差异无统计学意义（P>0.05）。结论：经过3个月长期毒性比较研究发现，达立通提取液颗粒和达立通提取液及回收液颗粒无明显毒性区别，无毒反应剂量均为8.75 g·kg-1，相当于体重60 kg成人临床用药剂量的16.7倍，毒性反应轻。

关键词: font-size:medium, ">长期毒性；达立通提取液颗粒；达立通提取液及回收液颗粒；安全性评价

Abstract: Objective： To observe and compre the long-term toxicity of dalitong granules from extracting solution and from extracting solution and recovery liquid during intragastric administration， so as to provide reference for clinical safe medication and resource reuse. Methods： SD rats were divided into 7 groups： the control group， dalitong granules (from extracting solution) 35.01， 17.51， 8.75 g·kg-1 group and dalitong granules (from extracting solution and recovery liquid) 35.01， 17.51， 8.75 g·kg-1 group. The growth， development， hematology， serum biochemistry and pathological changes of the rats in each group were observed after 3 months of continuous intragastric administration and 1 month of convalescence， and the toxicity of the two kinds of dalitong granules was compared. Results： The weight of male rats was higher than the control group， while female rats weight was just the opposite， and the difference of some observation points was statistically significant (P<0.05). The food intake of rats in each dose group tended to decrease with the administration time， and remained at a high level after one month recovery. The Neu% of the high dose group of male rats was decreased， and the Lym% of the high dose group of male rats was increased(P<0.05). PLT count in the middle and high dose groups of female rats were decreased(P＜0.05)， while recovered after withdrawal. ALT were cbserved decreased in high dose group of dalitong granules prepared from extracting solution and in low and medium dose groups of dalitong granules prepared from extracting solution and recovery liquid. AST were cbserved decreased in the administration group of dalitong granules prepared from extracting solution and and in low and medium dose groups of dalitong granules prepared from extracting solution and recovery liquid. TG was increased in low and medium dose groups of dalitong granules prepared from extracting solution and recovery liquid (P<0.05)， and returned to normal level after one month recovery. The liver coefficient of male rats in middle and high dose groups and female in high dose groups were increased after administration (P<0.05)，while recovered after withdrawal. Histopathological observation shows hepatic punctate necrosis which has no difference compared with the control group(P>0.05). Conclusion： After a 3-month long-term toxicity comparison study， we found that there was no significant difference in toxicity between dalitong granules prepared from extracting solution and prepared from extracting solution and recovery liquid， and the non-toxic reaction dose of the two drugs was 8.75 g·kg-1， equivalent to 16.7 times of the clinical dose of 60 kg adult， and the toxic reaction was light.

Key words: font-size:medium, ">Long-term toxicity； Dalitong granules from extracting solution； Dalitong granules prepared from extracting solution and recovery liquid； Safety evaluation

中图分类号:

张俊明, 周艳艳, 郭晟, 郑国安, 徐丽瑛, 伍锡栋, 丁琦. 达立通提取液颗粒、达立通提取液及回收液颗粒灌胃给药安全性评价[J]. 中国医药导刊, 2023, 25(5): 549-556.

ZHANG Junmin, ZHOU Yanyan, GUO Sheng, ZHENG Guoan, XU Liying, WU Xidong, DING Qi. Safety Evaluation of Intragastric Administration of Dalitong Granules from Extracting Solution and Prepared from Extracting Solution and Recovery Liquid[J]. CHINESE JOURNAL OF MEDICINAL GUIDE, 2023, 25(5): 549-556.

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