基于微乳凝胶新载体的丹皮酚经皮给药系统的构建及药代动力学研究  

The preparation of paeonol transdermal delivery systems based on the microemulsion-based gels and its pharmacokinetics characters

作　　者：刘继勇[1,2] 韩盈[2] 胡晋红[2] 王峥涛[1] 陈凯先[1] 

机构地区：[1]上海中医药大学中药研究所,上海201203 [2]第二军医大学长海医院药学部,上海200433

出　　处：《药学学报》2012年第2期244-249,共6页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目(30801557);中国博士后科学基金资助项目(20100470033);上海市博士后基金资助项目(11R21415600)

摘　　要：为构建基于微乳凝胶(microemulsion-based gels,MBGs)新载体的丹皮酚经皮给药系统,采用皮肤、血液双位点同步微透析结合LC/MS联用技术测定丹皮酚微乳、微乳凝胶及市售丹皮酚软膏在大鼠皮肤、血液中的药物浓度随时间的变化过程,并对其药代动力学参数进行比较分析。方法学研究表明,丹皮酚线性探针体内回收率(Rin vivo)为(69.7±4.8)%,同心圆探针体内回收率为(51.6±7.2)%。大鼠腹部脱毛,分别给予丹皮酚微乳(1%丹皮酚)、微乳凝胶和市售丹皮酚软膏,以PBS(pH 7.4)溶液作为灌流液,灌流速度为5μL.mL?1,每隔20 min收集1次微透析样品,共收集12 h,透析液采用LC/MS进行测定。皮肤药动学结果表明丹皮酚微乳、微乳凝胶与市售软膏相比,显著提高了药物在皮肤组织中的浓度;血液药动学结果表明微乳凝胶与市售软膏具有相近的生物利用度,但前者的血药浓度更平稳。本研究所构建的丹皮酚微乳凝胶有望为皮肤湿疹的治疗提供一种新的制剂;所建立的微透析/LC-MS联用技术能够在体、同步、实时监测大鼠皮肤、血液中的药物浓度,为经皮给药药代动力学研究提供了新的方法。Investigation of the pharmacokinetics of paeonol microemulsion, microemulsion-based gels and marketed paeonol ointments by the skin-blood synchronous microdialysis coupled with LC/MS is reported in this study. The microdialysis systems were established by linear probes and concentric circles probes. In vivo recovery of paeonol in skin is （69.7 ±4.8） % and in blood is （51.6 ± 7.2） %. The paeonol microemulsion, microemulsion-based gels and marketed paeonol ointments were administered to rats. PBS （pH 7.4） served as perfused solution. The perfusion rate was 5 μL·mL^-1 and the microdialysis samples were collected every 20 min intervals. The paeonol concentration in perfused solution was determined by LC/MS. The results showed that paeonol microemulsion and microemulsion-based gels significantly raised the drug concentrations in skin more than that of paeonol ointments. The paeonol microemulsion-based gels has similar bioavailability as the paeonol ointments in blood, but its blood drug concentrations were steadier. The paeonol microemulsion-based gels may be developed into a new preparation for dermis eczema. The skin-blood synchronous microdialysis technique proved to be a new method for the pharmacokinetics study of transdermal delivery systems.

关 键 词：丹皮酚 微乳凝胶 微透析 经皮给药 药代动力学 

分 类 号：R943[医药卫生—药剂学]