西罗莫司乳膏的制备及其药效学研究

Preparation and Pharmacodynamics of Sirolimus Cream

目的:制备西罗莫司乳膏并探究其对小鼠慢性皮炎湿疹模型的疗效。方法:制备O/W型西罗莫司乳膏并建立制剂的含量测定方法。选取70只SD小鼠分为7组,分别为空白对照组,模型组,西罗莫司低(0.1%)、中(0.5%)、高(1%)剂量组,他克莫司组和吡美莫司组。除空白对照组外,其余各组制备小鼠慢性皮炎湿疹模型,采用7%2,4-二硝基氯苯丙酮溶液致敏,0.3%2,4-二硝基氯苯溶液多次激发。各组于致敏后开始给药,2次/d,持续14 d,以小鼠耳朵肿胀度为指标,并采用ELISA法测定血清中IFN-γ、IL-4等细胞因子的浓度。结果:制得的西罗莫司乳膏匀展性好,西罗莫司在1.0~100.0μg·ml^(-1)浓度范围内线性关系良好(r=0.999 9),平均回收率为99.7%,RSD为0.7%(n=9)。西罗莫司乳膏能显著抑制小鼠耳朵肿胀度(P<0.05),改善小鼠耳部的红肿情况(P<0.01),同时促进小鼠血清中IFN-γ的表达,并降低IL-4的表达。结论:药效学实验表明,西罗莫司对小鼠慢性皮炎湿疹有一定疗效,为西罗莫司外用制剂的研究提供了实验依据。

Objective： To prepare sirolimus cream and explore its curative effect on chronic dermatitis eczema in mouse model.Methods： The O / W type of sirolimus cream was prepared and the determination method was established. Totally 70 SD mice were divided into 7 groups,the blank control group,the model group,sirolimus low（ 0.1%）,medium（ 0.5%） and high dose group（ 1%）,tacrolimus group and pimecrolimus group. Except the blank control group,the other groups were with the model of chronic dermatitis eczema sensitized by 7% 2,4-2 nitrochlorobenzene acetone solution and multiple excited by 0.3% 2,4-2 nitrochlorobenzene solution.After the sensitization,each group was respectively treated with the drug,twice a day,for 14 days,and the mouse ear swelling degree was used as the index,and an ELISA method was used to determine the levels of cytokine IFN-γ and IL-4 in serum. Results： The cream had good uniformity of development. Sirolimus had a good linear relationship within the range of 1.0-100.0 μg ·ml^（-1）（ r =0.999 9）.The average recovery was 99.7% and RSD was 0.7%（ n = 9）.Sirolimus cream could significantly inhibit the mouse ear swelling degree（ P〈0.05） and relieve the swelling（ P〈0.01）,and promote the expression of IFN-γ and reduce the expression of IL-4 in serum. Conclusion： The pharmacodynamics experiments show that sirolimus has certain curative effect on chronic dermatitis eczema in mouse model,which provides experimental basis for the study of sirolimus external preparation.