盐酸小檗碱微乳凝胶贴的制备及药动学与药效学研究  

Preparation,Pharmacokinetics and Pharmacodynamics of Berberine Hydrochloride Microemulsion Gel Patch

作　　者：顾雪梅 汪洁 吕志阳 蒋晓凡 王建茹 翟亚茹 GU Xuemei;WANG Jie;LÜZhiyang;JIANG Xiaofan;WANG Jianru;ZHAI Yaru(School of Pharmacy,Nanjing University of Chinese Medicine Hanlin College,Taizhou 225300,China;School of Pharmacy,Jiangsu Food Pharmaceutical Science College,Huaian 223003,China)

机构地区：[1]南京中医药大学翰林学院药学院,江苏泰州225300 [2]江苏食品药品职业技术学院药学院,江苏淮安223003

出　　处：《中国药学杂志》2025年第5期497-506,共10页Chinese Pharmaceutical Journal

基　　金：2024年江苏高校青蓝工程优秀教学团队项目资助;2023年江苏省大学生创新创业项目资助(202313981002Y,202313981003Y);泰州市科技支撑项目资助(TS202232;TS202325)。

摘　　要：目的 制备盐酸小檗碱微乳凝胶贴,以提高药物的相对生物利用度。方法 首先筛选微乳材料,采用星点设计-效应面法优化出微乳处方,并进行质量评价;其次,筛选并优化凝胶贴的处方工艺。开展体外透皮试验研究,并对其进行大鼠体内药动学和小鼠药效学研究。结果 制备出盐酸小檗碱微乳凝胶贴,其中微乳的最佳处方为油相-乳化剂-助乳化剂=0.11∶0.6∶0.3,凝胶贴的最佳处方为NP700-甘油-甘羟铝=2.3∶17.5∶0.1。离体皮肤透皮实验结果表明,质量分数为3%的氮酮促渗效果最优。药动学表明,微乳凝胶贴能延长体内作用时间,药效学表明,给药后能有效改善皮肤皮损情况、明显抑制炎症因子含量的升高及改善病理组织情况。结论 盐酸小檗碱微乳凝胶贴可有效改善盐酸小檗碱经皮吸收生物利用度。OBJECTIVE To prepare berberine hydrochloride microemulsion gel patch to improve the in vitro transdermal penetration and relative bioavailability in vivo.METHODS Firstly,through the screening of microemulsion dressing materials,and using the central point design response surface optimization method to optimize the microemulsion prescription,the best microemulsion prescription was obtained.The morphology and particle size of microemulsion were investigated by laser particle size analyzer and transmission electron microscope.Secondly,the matrix was selected for the gel paste,and then the optimal design of the gel paste was obtained by using the star design response surface optimization method.Finally,the microemulsion was added to the gel paste to prepare the berberine hydrochloride microemulsion gel paste,and the prescription process was verified.Through the in vitro transdermal test of mice,by comparing the permeation promoting effect of different concentrations of zzone,draw the cumulative permeation amount time curve of azone with different concentrations,and select the best amount of Azone.Finally,pharmacokinetic studies in rats and pharmacodynamic studies in mice were conducted.RESULTS Berberine hydrochloride microemulsion gel paste was successfully prepared.The best formulation of microemulsion was oil phase-emulsifier-co-emulsifier=0.11∶0.6∶0.3.The morphology and particle size of microemulsion were investigated by laser particle size analyzer and transmission electron microscope.The RESULTS showed that most microemulsion morphology was round,regular spherical,no aggregation,and the particle size was appropriate.The best prescription of gel paste NP700∶glycerol-dihydroxyaluminum aminoacetate=2.3∶17.5∶0.1 aluminum glycinate.The RESULTS of in vitro skin penetration test showed that azone with a mass fraction of 3%had the best penetration promoting effect.Pharmacokinetics showed that berberine hydrochloride microemulsion gel patch could prolong the action time in vivo.Preliminary pharmacodynamics show

关 键 词：盐酸小檗碱 微乳凝胶贴 星点设计-效应面法 药动学 药效学 

分 类 号：R944[医药卫生—药剂学]