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基于双位点同步微透析技术的青藤碱微乳凝胶皮肤及血液药代动力学研究
作者姓名:丁杨  钱珊珊  郭健  桂双英
作者单位:1.安徽中医药大学药学院, 安徽 合肥 230012
基金项目:国家自然基金面上项目81873019安徽高校自然科学研究项目KJ2021A0541
摘    要:  目的  采用双位点同步微透析技术研究青藤碱微乳凝胶(Sinomenine-loaded microemulsion gel, SMG)的大鼠皮肤与血液药代动力学过程, 探究SMG的经皮药代动力学特征。  方法  建立青藤碱的超高液相色谱(UPLC)含量测定方法, 开展专属性、线性、精密度、回收率等方法学考察。SD大鼠经麻醉, 腹部脱毛处理后, 植入线性探针和血液探针, 局部涂抹青藤碱微乳凝胶, 采用微透析技术结合UPLC技术测定皮肤和血液透析液中青藤碱浓度。  结果  青藤碱的UPLC分析方法在0.5~20 μg·mL-1浓度范围内线性良好, 色谱的专属性、精密度及回收率等均符合微透析样品检测要求。药代动力学研究中青藤碱在皮肤中Cmax为(10.91±3.05)μg·mL-1, Tmax为(180.00±39.80)min, AUC0→t为(736.51±45.30)μg·min·mL-1; 在血液中Cmax为(6.74±1.91)μg·mL-1, Tmax为(239.98±40.85)min, AUC0→t为(426.43±30.18)μg·min·mL-1。  结论  SMG经皮给药后能够缓慢持续释放青藤碱, 可在皮肤中形成储库效应。 

关 键 词:经皮给药    青藤碱    微乳凝胶    微透析    探针    经皮药代动力学
收稿时间:2022-08-15

Pharmacokinetic Study of Skin and Blood of Sinomenine-Loaded Microemulsion Gel Based on Double Sites Simultaneous Microdialysis
Institution:1.College of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012, China2.Institute of Pharmaceutics, Anhui Academy of Chinese Medicine, Hefei 230012, China3.Engineering Technology Research Center of Modernized Pharmaceutics Anhui Education Department, Hefei 230012, China4.Anhui Province Key Laboratory of Pharmaceutical Preparation Technology and Application, Hefei 230012, China5.The Second Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei 230061, China
Abstract:  OBJECTIVE  To investigate the pharmacokinetics of sinomenine-loaded microemulsion gel (SMG) by skin and blood microdialysis in rats, and explore the pharmacokinetic characteristics of SMG.  METHODS  An UPLC method for the determination of sinomenine was established, and its specificity, linearity, precision and recovery rate were examined. The probe was implanted after the rats were anesthetized and depilated, then the sinomenine microemulsion gel was applied onto the bare abdominal skin of the rats. The microdialysis technique and UPLC were used to determine the concentration of the drug.  RESULTS  The results showed that the established method for the determination of sinomenine microemulsion gel was well linear in the range of 0.5-20 μg·mL-1, and the specificity, degree of precision and recovery rate of the chromatography all conformed to the examination requirements of microdialysis samples.The results of pharmacokinetic study showed that the Cmax values of sinomenine in skin and blood were (10.91±3.05) and (6.74±1.91)μg·mL-1, respectively. The Tmax values were (180.00±39.80) and (239.98±40.85)min, respectively. And the AUC0→t values were (736.51±45.30) and (426.43±30.18)μg·min·mL-1.  CONCLUSION  The sinomenine microemulsion gel plays a role in forming skin reservoir through percutaneous penetration, and can control the sustained release of drug. 
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