小儿水杨酸苯酚搽剂的毒理学研究

Study on Toxicology of Salicylic Acid-Phenol Liniment for Children

目的:为小儿水杨酸苯酚搽剂成品制剂的临床安全使用提供实验依据。方法:观察大鼠完整皮肤及破损皮肤一次性涂抹最大耐受量(MTD)的小儿水杨酸苯酚搽剂所产生的毒性反应情况,从给药0时起至7d连续观察记录动物的急性毒性和45d连续的长期毒性反应,以皮肤刺激反应标准进行评分作毒理等级评价;对存活动物在观察结束时进行高位脱椎处死采血检测外周血常规和血清生化,解剖后裸眼和病理切片观察心、脑、肝、肾等主要脏器的病理变化。实验数据以Bliss法处理计算LD50。结果:未测出LD50值;皮肤完好与破损组动物均产生轻度刺激反应;外周血常规和血清生化均未见明显改变;心、脑、肝、肾等重要脏器裸眼和病理切片均未见明显病理改变。结论:小儿水杨酸苯酚搽剂在小于MTD2000mg/(kg.d)[40mL/(kg.d)]剂量下一次性涂大鼠皮肤后(该剂量相当于临床剂量的800倍)以及1000、500、200mg/(kg.d)剂量的长期毒性试验,均未产生明显毒副反应。

Objective： To provide scientific foundation for safely using Salicylic Acid-Phenol Liniment. Methods： Integrated and disrepaired skins in the rats were smeared with Salicylic Acid-Phenol Liniment by the maximum tolerated dose （MTD） only. The toxic reaction of the animals were observed and recorded continuously from the beginning of using the drug to 7 days, and evaluated by using the general standard of the reaction of skin stimulation in pharmacology. Animals were executed by taking off acanthi and blood was collected to check up the periphery blood routine and serum biochemistry at the end of the observation of the rats. And after the dissection, the pathological change of main visceras, such as heart, brain, liver and kidney were observed with naked eye and pathological slices. The data of this experiment was used to calculate the value of LD50 by using Bliss rule. Results： The value of LD50 was unavailable to be calculated. Low-grade stimulation was observed in both integrated and disrepaired groups. There was no obvious changes in the periphery blood routine, serum biochemistry and pathological slices in the main visceras （heart, brain, liver and kidney）. Conclusions： There are no obvious toxic reactions occurred to the rats by the doses 1 000,500,200 mg·kg^-1·d^-1 and smearing Salicylic Acid-Phenol Liniment one time, whose dose was lower than MTD 2 000 mg·kg^-1·d^-1 （40 mL·kg^-1·d^-1）.