黄连-干姜有效组分自微乳给药系统的制备与评价  

Preparation and evaluation of self-microemulsion drug delivery system for effective components of Coptidis Rhizoma-Zingiberis Rhizoma

作　　者：李鑫 余玲 刘葭[1] 梅凯 李婷婷 郝逗逗 王昕怡 王灵敏 吴清[1] LI Xin;YU Ling;LIU Jia;MEI Kai;LI Ting-ting;HAO Dou-dou;WANG Xin-yi;WANG Ling-min;WUQing(School of Chinese Materia Medica,Beijing University of Chinese Medicine,Beijing 102488,China;Jiangxi Medical College,Shangrao 334000,China)

机构地区：[1]北京中医药大学中药学院,北京102488 [2]江西医学高等专科学校,江西上饶334000

出　　处：《中草药》2023年第1期51-61,共11页Chinese Traditional and Herbal Drugs

基　　金：国家自然科学基金项目(81773915)。

摘　　要：目的研究黄连-干姜有效组分自微乳给药系统(Coptidis Rhizoma-Zingiberis Rhizoma effective component self-microemulsion drug deliverysystem,Cop-Gin-SMEDDS)的处方与制备工艺,并且进行体外质量评价。方法通过溶解度实验、伪三元相图的绘制和D-最优混料设计确定Cop-Gin-SMEDDS的最佳处方组成;通过单因素考察,确定最佳制备工艺,并对Cop-Gin-SMEDDS理化性质、稳定性、体外释放等进行评价。结果最终确定Cop-Gin-SMEDDS的最优处方(不含黄连总生物碱)为油酸5%,1,2-丙二醇41%,聚氧乙烯(40)氢化蓖麻油49%,干姜油5%;黄连总生物碱的投药量为5%;最佳制备工艺为在37℃、转速300 r/min条件下磁力搅拌10 min。得到的Cop-Gin-SMEDDS为深红色澄清透明液体,稀释后为黄色、均一透明的微乳溶液;透射电镜下为圆球形,大小均匀,形态规则;平均粒径大小为(22.21±0.45)nm、多分散指数(polydispersity index,PDI)为0.195±0.019、ζ电位为(−2.67±0.11)mV。Cop-Gin-SMEDDS中盐酸小檗碱、盐酸巴马汀、盐酸黄连碱、表小檗碱及6-姜辣素的载药量分别为(13.51±0.71)、(1.37±0.06)、(2.36±0.27)、(0.83±0.14)、(6.34±0.04)mg/g,包封率分别为(96.36±0.34)%、(95.49±0.59)%、(92.56±0.81)%、(95.17±0.39)%、(94.39±1.63)%。Cop-Gin-SMEDDS中盐酸小檗碱在pH 7.4 PBS缓冲液、蒸馏水和pH 1.2盐酸溶液中的24 h累积释放率分别为(70.80±0.04)%、(96.17±0.10)%、(85.77±0.10)%;6-姜辣素在相应释放介质中的24 h累积释放率分别为(27.70±0.14)%、(32.48±0.14)%、(32.96±0.07)%。稳定性实验显示,将Cop-Gin-SMEDDS在不同温度下放置30 d后其指标成分及外观性状均无明显变化。结论制备的Cop-Gin-SMEDDS外观良好,载药量和包封率高,能提高药物的稳定性和释放量,有望进一步开发制备成口服给药制剂。Objective To study the formulation and preparation technology of self-microemulsion drug delivery system of effective components of Huanglian(Coptidis Rhizoma)-Ganjiang(Zingiberis Rhizoma)(Cop-Gin-SMEDDS), and evaluate it. Methods The best prescription composition of Cop-Gin-SMEDDS was determined by solubility experiment, pseudo ternary phase diagram drawing and D-optimal mixture design. Through single factor investigation, the optimal preparation process was determined, and the physicochemical properties, stability and in vitro release of Cop-Gin-SMEDDS were evaluated. Results The optimal prescription of Cop-Gin-SMEDDS(excluding total alkaloids of Coptidis Rhizoma) was oleic acid 5%, 1,2-propanediol 41%, polyoxyethylene(40) hydrogenated castor oil 49%, dried ginger oil 5%. The dosage of coptis alkaloids was 5%. The optimum preparation process was magnetic stirring at 37 ℃ and 300 r/min for 10 min. The obtained Cop-Gin-SMEDDS was a dark red clear and transparent concentrate, and after dilution, it was a yellow, homogeneous and transparent microemulsion solution. Under transmission electron microscope, it was round and spherical, with uniform size and regular shape. The average particle size was(22.21 ± 0.45) nm, PDI was 0.195 ± 0.019, and ζ potential was(-2.67 ± 0.11) mV. The drug loading of berberine hydrochloride, palmatine hydrochloride,coptisine hydrochloride, epiberberine and 6-gingerol in Cop-Gin-SMEDDS were(13.51 ± 0.71),(1.37 ± 0.06),(2.36 ± 0.27),(0.83 ±0.14) and(6.34 ± 0.04) mg/g, respectively. The encapsulation efficiency were(96.36 ± 0.34)%,(95.49 ± 0.59)%,(92.56 ± 0.81)%,(95.17 ± 0.39)% and(94.39 ± 1.63)%, respectively. The 24 h cumulative release rates of berberine hydrochloride in Cop-GinSMEDDS in pH 7.4 PBS buffer, water and pH 1.2 hydrochloric acid solution were(70.80 ± 0.04)%,(96.17 ± 0.10)%, and(85.77 ±0.10)%, respectively;the 6-gingerol in corresponding release media were(27.7 ± 0.14)%,(32.48 ± 0.14)% and(32.96 ± 0.07)%,respectively. The stability experiment showed that t

关 键 词：干姜油 黄连总生物碱 自微乳给药系统 伪三元相图 D-最优混料设计 黄连 干姜 盐酸小檗碱 盐酸巴马汀 盐酸黄连碱 表小檗碱 6-姜辣素 

分 类 号：R283.6[医药卫生—中药学]