不同处方工艺的复方醋酸地塞米松乳膏的裸鼠皮肤药动学行为比较

发布时间：2018-03-09 17:20

本文选题：醋酸地塞米松　切入点：乳膏　出处：《中国药学杂志》2015年14期 　论文类型：期刊论文

【摘要】：目的利用裸鼠在体皮肤给药,比较3种不同处方工艺的醋酸地塞米松乳膏皮肤药动学行为,同时探讨裸鼠在体皮肤药动学方法的应用前景。方法选择裸鼠背部皮肤在体涂复方醋酸地塞米松乳膏约0.025 g后,于0、0.25、0.75、1.75、3、5、8、12、24 h后去除残余药物,取皮,称重,甲醇匀浆沉淀蛋白,采用高效液相色谱-电喷雾离子质谱联用法(LC-ESI-MS)测定裸鼠皮肤中的醋酸地塞米松浓度,计算药动学参数,同时对三种乳膏裸鼠经皮吸收的行为进行评价。结果该测定方法没有内源性物质干扰,醋酸地塞米松皮肤匀浆液浓度在0.052 4~5.24μg·m L-1内,线性关系良好。3种浓度的回收率分别是95.97%、89.95%、91.72%,精密度的RSD均15%,样品的稳定性良好。经测定,处方中含二甲基亚砜(DMSO)能增加醋酸地塞米松的皮肤药动学参数AUC值,而乳膏粒度大、有结晶则减少醋酸地塞米松的皮肤药动学参数AUC值。结论 LC-ESIMS分析方法快速、灵敏、准确,回收率高,重现性好,检测限低,可成功的用于测定醋酸地塞米松在裸鼠皮肤中的浓度,较好地反映醋酸地塞米松在裸鼠皮肤中的经皮吸收行为,裸鼠在体给药分时取样法可用于临床前外用药物的皮肤药动学筛选与评价。
[Abstract]:Objective to compare the skin pharmacokinetics of dexamethasone acetate cream in nude mice. At the same time, the application prospect of pharmacokinetic method of skin in vivo in nude mice was discussed. Methods after applying compound dexamethasone acetate cream to the skin of nude mice in vivo about 0.025 g, the residual drugs were removed, skin removed, weighed, and methanol homogenate precipitated protein was removed after 24 hours. The concentration of dexamethasone acetate in skin of nude mice was determined by high performance liquid chromatography-electrospray ion-mass spectrometry (HPLC / ESI-MS), and the pharmacokinetic parameters were calculated. Results the skin homogenate concentration of dexamethasone acetate was 0.0524 渭 g 路mL ~ (-1), the concentration of dexamethasone acetate skin homogenate was 0.0524 渭 g 路mL ~ (-1). The recoveries of different concentrations of Dexamethasone acetate and dexamethasone acetate were 95.97, 89.95 and 91.72, respectively, and the precision of RSD was 15, and the stability of the samples was good. The results showed that DMSO in the prescription could increase the AUC value of skin pharmacokinetics of dexamethasone acetate, but the size of cream was large. The skin pharmacokinetic parameter AUC value of dexamethasone acetate was reduced by crystallization. Conclusion the LC-ESIMS method is rapid, sensitive, accurate, high recovery, good reproducibility and low detection limit. It can be used to determine the concentration of dexamethasone acetate in the skin of nude mice and reflect the percutaneous absorption behavior of dexamethasone acetate in nude mice skin. The method of time-sharing sampling in vivo can be used to screen and evaluate the skin pharmacokinetics of preclinical drugs for external use in nude mice.
【作者单位】：中国医学科学院皮肤病研究所;
【基金】：中央级公益性科研院所基本科研业务专项资助项目(2011PYS003) 南京药学会-常州四药医院药学科研基金资助项目(2013YX013)
【分类号】：R965

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