【摘要】 目的考察多塞平乳膏经皮肤用药的安全性。方法①取家兔6只,随机分为完整皮肤组和破损皮肤组各3只,实验开始前24 h脱毛并制作破损皮肤模型,采用同体左右侧自身对比法,脊柱左侧上半部涂5%多塞平乳膏,左侧下半部涂10%多塞平乳膏,脊柱右侧上半部涂基质,右侧下半部为空白对照,观察多塞平乳膏的单次皮肤刺激性;另取家兔6只,分组及皮肤处理方法同上,每日给药1次,连续给药7 d,观察多塞平乳膏的多次皮肤刺激性。②取家兔32只,随机分成10%,20%,30%多塞平乳膏3个剂量组和基质组,每组8只(完整皮肤和破损皮肤组各4只)。于给药前24 h脱毛并制作破损皮肤模型。将10%,20%,30%多塞平乳膏和基质各10 g均匀地涂于相应各组家兔背部脱毛区,24 h后洗净残留药物。连续14 d观察多塞平乳膏的皮肤急性毒性反应。③取豚鼠30只,随机平均分为3组,每组10只。取5%多塞平乳膏和基质各0.2 g,阳性致变态反应物(1%的2,4-二硝基氯苯,用75%乙醇配制)0.2 mL,分别涂于豚鼠脊柱左侧脱毛区,固定6 h后洗去受试物,在第7和第14天以同样方法各重复1次,观察药物所致的豚鼠皮肤变态反应。末次给受试物致变态反应后第14天,将多塞平乳膏0.2 g涂于豚鼠背部右侧脱毛区,6 h后去掉受试物,即刻观察,然后于24,48,72 h再观察皮肤变态反应情况;将基质0.2 g及阳性致变态反应物0.2 mL涂于豚鼠背部右侧脱毛区,6 h后去掉受试物,观察多塞平乳膏导致的皮肤变态反应。结果单次和多次给予多塞平乳膏对家兔完整和破损皮肤均无刺激作用;给予10%,20%,30%多塞平乳膏和基质后,未见该药对家兔有明显毒性作用。给予30%多塞平乳膏组家兔在涂药5 h后有轻微嗜睡现象,12 h后恢复正常。豚鼠皮肤未见变态反应。结论多塞平乳膏对家兔皮肤无明显刺激性和毒性作用,对豚鼠皮肤无明显致变态反应作用。更多还原

【Abstract】 Objective To inspect the safeness of percutaneous application of doxepin hydrochloride cream（DHC） in animals. Methods Experiment①: 6 rabbits were randomly divided into 2 equal groups: intact skin group and dermal injury group.24 h before the beginning of the experiment,rabbits of both groups were subjected to localized depilation of the skin of the back to the left and right of the spine.Dermal injury was produced by scraping the skin with a sterilized needle until oozing of blood began to appear.An auto-contrast method was adopted in which changes in the skin on both sides of the spine of the same animal were compared.In rabbits of both groups,the upper part of the depilated area to the left of the spine was smeared with 5%DHC while the lower part was painted with 10% DHC.The upper part of the depilated area to the right of the spine was smeared with the ground substance of the cream while the lower part was left for blank control.Skin irritation caused by the single application of DHC was kept under observation.Another 6 rabbits were divided and treated as described above except that DHC and control substances were applied once daily for 7 consecutive days.Skin irritation caused by repeated applications of DHC was kept under observation.Experiment ②:32 rabbits were randomly divided into 4 equal groups each of which was subdivided into 2 subgroups,the intact skin subgroup and the dermal injury subgroup.24 h before the experiment,the animals were depilated and dermal injury was produced as described in experiment ①.10 g of 10%,20% and 30% DHC were smeared onto the depilated skin areas of each of the rabbits of the 3 groups,respectively.Equivalent amounts of ground substance were applied similarly for rabbits of the 4^th group.24 h.later,the remnants of the drug and ground substance were washed away.Acute toxic skin reactions of DHC were kept under observation for 14 consecutive days.Experiment ③: 30 guinea pigs were randomly divided into 3 equal groups.0.2 g of 5% DHC,0.2 g of ground substance and 0.2 mL of allergen（1% 4-DNCB in 75% ethanol） were smeared onto the depilated skin of each of the animals of the 3 groups,respectively.The test substances were washed away 6 h later.The experiment was repeated on day 7 and day 14.Skin allergic reactions caused by the drugs were kept under observation.14 days after the last smearing of the drugs,0.2 g of DHC was smeared onto the right depilated area of each of the guinea pigs.The test substances were washed away 6 h.later and skin allergic reactions were kept under observation immediately and 24,48 and 72 h.after the washing,respectively.0.2 g of ground substance and 0.2 mL of 0.1%DNCB were similarly applied onto the right depilated areas of guinea pigs for control. Results No irritative dermal reaction in intact or injured skin was induced by single or repeated applications of DHC.No major toxic effects were observed after the applications of 10%,20% and 30% DHC.5 h after the smearing of 30% DHC,slight somnolence was observed in the rabbits,which faded away 12 h.afterwards.No allergic skin reactions were induced by DHC in guinea pigs. Conclusion DHC was shown to exert no apparent irritative or toxic effects on the skin of rabbits,nor allergic skin of reactions in guinea pigs.更多还原