水飞蓟宾口服亚微乳剂的制备及大鼠体内药动学研究

摘要

目的:制备水飞蓟宾口服亚微乳并研究其在大鼠体内的药动学.方法:采用薄膜分散-探头超声法制备水飞蓟宾亚微乳.大鼠分别灌服水林佳(市售水飞蓟宾磷脂复合物胶囊)和水飞蓟宾亚微乳,于不同时间点取血,HPLC法测定血药浓度,采用DAS (Date Acquisition System)软件求算药动学参数.结果:水飞蓟宾亚微乳制剂的平均粒径为(155.9±2.2) nm,Zeta电位为-(29.62±0.03) mV,体外释放动力学符合Weibull方程;大鼠灌服水林佳和水飞蓟宾亚微乳后MRT分别为(1.73±0.03)h和(3.44±0.08)h,AUC0-∞分别为(1.83±0.38) mg· h· L-1和(4.72±0.48)mg·h·L-1.水飞蓟宾亚微乳的相对生物利用度为257.9％.结论:水飞蓟宾制成亚微乳制剂后延长了药物在体内的滞留时间,提高了药物的口服生物利用度.%Objective:To prepare a silybin oral submicron emulsion and evaluate its pharmacokinelic profile in rats.Methods:The silybin submicron emulsion was prepared by a membrane dispersion-ultrasonic method.Following the oral administration of silybin hard capsules or silybin submicron emulsion into rats, the blood samples were collected at different times and the plasma silybin concentrations were then quantified by HPLC.The pharmacokinetic parameters were calculated by the DAS software.Results:The size of silybin submicron emulsion was determined to be (155.9+2.2) nm and the Zeta potential was -(29.62±0.03) mV.The MRT values of silybin hard capsules and silybin submicron emulsion were (1.73± 0.03) h and (3.44±0.08) h, the AUC0- values were (1.83±0.38) mg-h·L-1 and (4.72±0.48) mg-h·L-1, respectively.The relative bioavailability of silybin submicron emulsion was 257.9%.Conclusion:Compared with the hard capsules, submicron emulsion significantly elongated the retention time, enhanced the absorption and improved the bioavailability of silybin in rats.