紫连膏经家兔皮肤单次给药毒性研究

Study on Single-Dose Toxicity of Zilian Cream in New Zealand Rabbit Skin

目的 观察紫连膏经家兔皮肤给药的急性毒性反应及其严重程度,为临床用药提供参考。方法 新西兰家兔24只,随机分为完整皮肤2组和破损皮肤模型2组,即正常对照组、正常紫连膏组、模型对照组和模型紫连膏组,每组6只,雌、雄各半。各组均按经体质量折算的10%家兔体表面积,以50 mg·(cm^(2))^(-1)的给药面积皮肤涂擦白凡士林和紫连膏[折合以体质量计的总给药剂量为12.50 g·kg^(-1),单位面积给药剂量为150 mg·(cm^(2))^(-1),相当于10%人体表面积拟用剂量的5倍],24 h内给予3次,每次间隔(4.0±0.5) h。给药并连续观察14 d。观察家兔的一般情况、给药局部皮肤刺激性及体质量、体温、血常规、血清生化及电解质,大体解剖观察各脏器的体积、颜色、质地等情况。结果 给药各组家兔一般情况良好,给药局部皮肤无明显刺激,体质量、体温、血常规、血清生化及电解质无异常,主要脏器无异常改变。结论 紫连膏在单次毒性实验最大给药量条件下,家兔未发生刺激和毒性反应。

Objective To evaluate the acute toxicity reaction and severity of Zilian cream on percutaneous topical administration in rabbits,and to provide a reference for dose design of repeat dose toxicity study and clinical medication safety.Methods Twenty-four New Zealand rabbits were randomly divided into two normal skin groups and two model groups which back topical skin be injured with sandpaper,namely the normal control group,the normal Zilian cream group,the model control group,and the model Zilian cream group,three female and three male rabbits in each group.The corresponding drugs were percutaneously given three times in 24 h to rabbits with a volume of 50 mg·(cm^(2))^(-1)(12.50 g·kg^(-1) of the total dose,and equivalent to 5 times of proposed clinical dosage in 10%body surface area of human)at(4.0±0.5)h interval.General symptoms,signs,and administrated topical skin irritation of rabbits were observed every day for 14 days.During the different study periods,the body mass was weighed,the temperature was measured,and routine blood test indexes,and serum biochemical and electrolytes indexes were detected in rabbits of groups.After dissecting rabbits at the end of the study,the volume,color,and texture of organs were observed if there were abnormalities.Results The rabbits in each group were generally in good condition,and there was no obvious skin irritation to topical skin in rabbits.The detected results of body mass,temperature,routine blood test indexes,serum biochemical and electrolytes indexes were not abnormal,and pathological changes were not observed in the main organs.Conclusion Zilian cream does not show significantly toxic and irritation reactions in the maximal feasible dose(MFD)in rabbits.