999感冒灵颗粒及组分对小鼠急性毒性和饥饿状态下肝毒性影响的研究  

Study on toxicity of 999 Ganmaoling grain and influence of diet on hepatic toxicity

作　　者：郭秋平 徐婷婷[2] 陈燕勤 甄滢滢 张跃飞 叶祖光[4] 金若敏[2] 

机构地区：[1]广州医药研究总院有限公司药物非临床评价研究中心,广东广州510240 [2]上海中医药大学药物安全评价研究中心,上海201203 [3]华润三九医药股份有限公司研发中心,广州深圳518110 [4]中国中医科学院中药研究所,北京100700

出　　处：《中国中药杂志》2016年第8期1397-1404,共8页China Journal of Chinese Materia Medica

基　　金：国家"重大新药创制"科技重大专项(2012ZX09201-201-001);国家重点基础研究发展计划(973)项目(2009CB522807)

摘　　要：比较999感冒灵全方及不同组分对小鼠急性毒性的影响,比较在饥饿和正常饮食状态下,感冒灵对小鼠肝毒性的影响。为临床安全性再评价及合理的安全使用提供实验依据。小鼠分别单次给予全方,化学药组分及中药组分,连续观察14 d,测定全方组与化学药组的LD_(50)和中药组最大耐受量;小鼠分为饥饿和饮食组,单次给予全方,观察14 d,计算LD_(50);小鼠分为饥饿和饮食组,单次给感冒灵后6 h检测血清生化指标和肝脏指数,计算TD50,观察肝脏组织形态。全方组LD50为4.42g·kg^(-1),化学药组LD_(50)为0.64 g·kg^(-1)。中药组最大耐受量接近24.24 g·kg^(-1)。全方组与化学药组小鼠的毒性表现基本相似,体重、摄食量有一定程度的下降,部分存活动物有肝、心组织病变;全方组表现程度较轻,恢复较快;饥饿组小鼠LD_(50)为2.56 g·kg^(-1),饮食组LD_(50)为6.93 g·kg^(-1);饥饿组小鼠肝TD_(50)为1.29 g·kg^(-1),饮食组小鼠肝TD_(50)为6.30 g·kg^(-1)。999感冒灵全方毒性较小,可能与中西药组分配伍后有一定的减毒作用有关。正常饮食状态和饥饿状态相比,小鼠LD_(50)及肝TD_(50)数值明显变大,毒性减小。从安全性角度提示在不饥饿状态或餐后服用感冒灵更为安全,上述试验为全方的临床安全使用提供了实验依据。This paper was aimed to compare the acute toxicity of 999 Ganmaoling grain and its different ingredients,and investigate the influence of routine diet on the hepatic toxicity induced by Ganmaoling in mice,so as to provide experimental basis for the clinical safety evaluation. Mice were given a single dose of Ganmaoling grain or its different ingredients respectively by gavage,and then observed for 14 days. LD50 values of Ganmaoling grain or its chemical ingredient and the maximal tolerated dose of its herb ingredient were determined. Mice were divided into starvation and diet group,a single dose of Ganmaoling grain was administered by gavage.LD50 values were estimated after 14 day observation. Mice were divided into starvation and diet group. At the same time,control group was set up for each. A single dose of Ganmaoling grain was given. Serum biochemical indexes were detected,liver weight index was calculated and liver tissue morphological change was observed after 6 h. LD50 values were 4. 42,0. 64 g·kg^-1 for Ganmaoling grain group and chemical ingredient group,respectively. The maximal tolerated dose of the herb ingredient group was close to 24. 24 g ·kg^-1. The toxic symptom was basically similar in the Ganmaoling grain and the chemical ingredient group. The body weight and food intake were decreased to a certain extent in both groups. There were pathological changes of liver and heart tissue in some of the surviving animals. The animals in the Ganmaoling grain group exhibited a lighter toxicity and recovered faster than that in the chemical ingredient group. LD50 values of Ganmaoling grain were 2. 56,6. 93 g·kg^-1 for starvation and diet group respectively. TD50 values were1. 29,6. 31 g·kg^-1 for starvation and diet group respectively. The toxicity of 999 Ganmaoling was less,which may be related to the reduction of toxicity after the combination of herb and chemical ingredients. Compared with starvation group,the values of LD50 and TD50 of diet group was significantly increased,and toxicity was decreased

关 键 词：感冒灵颗粒 组分 急性毒性 肝毒性 饥饿 饮食 

分 类 号：R285.5[医药卫生—中药学]