黄芩苷β-环糊精包合物脂质体的制备与药动学研究  

Preparation of baicalinβ-cyclodextrin inclusion complex liposomes and study on pharmacokinetics

作　　者：余清 YU Qing(Department of Pharmacy,Hubei 672 Traditional Chinese and Western Medicine Orthopedic Hospital,Wuhan 430070,China)

机构地区：[1]湖北六七二中西医结合骨科医院药学部,武汉430070

出　　处：《西北药学杂志》2021年第4期616-621,共6页Northwest Pharmaceutical Journal

摘　　要：目的制备黄芩苷β-环糊精(β-CD)包合物脂质体,并考察其在大鼠体内的药动学。方法采用饱和水溶液法制备黄芩苷β-CD包合物,以包合率作为评价指标,通过正交实验考察搅拌速度、水浴温度以及药物与载体质量比3个因素对黄芩苷β-CD包合物包合率的影响,并得到最佳制备工艺参数和处方;采用傅里叶红外变换光谱法(FTIR)确认了黄芩苷β-CD包合物的形成;采用薄膜-超声分散法制备黄芩苷β-CD包合物脂质体,并测定脂质体的粒径分布、Zeta电位以及在不同pH值介质环境中体外药物释放情况;通过Wister大鼠口服给予黄芩苷混悬液及黄芩苷β-CD包合物脂质体,分析比较2种制剂在大鼠体内的药动学。结果黄芩苷β-CD包合物的最佳工艺处方:搅拌速度为120 r·min^(-1),水浴温度为55℃,药物与载体质量比为1∶3;经FTIR图谱证实黄芩苷可被β-CD包合;黄芩苷β-CD包合物脂质体的平均粒径为(90.82±4.59)nm,Zeta电位为(-41.8±1.9)mV,黄芩苷β-CD包合物脂质体在不同pH值释放介质中均具有明显的缓释效果;黄芩苷β-CD包合物脂质体组在大鼠体内的药时曲线下面积(AUC(0~∞))、血药达峰质量浓度(C max)和半衰期(t 1/2)分别为黄芩苷混悬液组的2.15、0.78、2.16倍,说明将黄芩苷制备成β-CD包合物脂质体后可提高药物的生物利用度,延长其半衰期。结论制备的黄芩苷β-CD包合物脂质体具备一定的缓释性能,提高了黄芩苷的口服生物利用度,对黄芩苷新剂型的开发及临床研究具有重要意义。Objective To prepare baicalinβ-cyclodextrin(β-CD)inclusion complex liposomes and to investigate their pharmacokinetics in rats.Methods The baicalinβ-CD inclusion complex was prepared by saturated aqueous solution method.The inclusion rate was used as the evaluation index to investigate the agitation speed,water temperature and the mass ratio of drug to carrier through orthogonal experiments.The optimal preparation process was obtained.The formation of baicalinβ-CD inclusion complex was confirmed by Fourier transform infrared spectroscopy(FTIR).The film-ultrasonic dispersion method was used to prepare baicalinβ-CD inclusion complex liposomes.The particle size distribution,Zeta potential and drug release in vitro in different pH value media were investigated.The baicalinβ-CD inclusion complex liposomes and baicalin suspensions were orally administered to Wister rats and the pharmacokinetic parameters were compared.Results The optimal preparation conditions of baicalinβ-CD inclusion complex was as follows:stirring speed 120 r·min^(-1),water bath temperature 55℃,and mass ratio of drug to carrier 1∶3;The FTIR Spectrum confirmet that baicalin could be purifiedβ-CD inclusion.The average particle size of baicalinβ-CD inclusion complex liposomes was(90.82±4.59)nm,and Zeta potential was(-41.8±1.9)mV.The baicalinβ-CD inclusion complex liposomes showed obvious sustained-release effects in different pH release media.The in rats pharmacokinetic results showed that the AUC(0-∞),C max and t 1/2 of the baicalinβ-CD inclusion were 2.15,0.78 and 2.16 times than the baicalin suspension,indicating that the baicalinβ-CD inclusion complex liposomes could improve the bioavailability and prolong the half-life of baicalin in vivo.Conclusion The baicalinβ-CD inclusion compound liposome prepared in this study has a certain sustained-release performance,which improves the oral bioavailability of baicalin,and is of great significance to the development of new formulations of baicalin and clinical research.

关 键 词：黄芩苷 β-环糊精(β-CD) 包合物脂质体 药动学 生物利用度 

分 类 号：R94[医药卫生—药剂学]