水飞蓟素-羟丙基-β-环糊精包合物的制备及大鼠体内药动学评价  

Preparation of silymarin-hydroxypropyl-β-cyclodextrin inclusion complex and its pharmacokinetics evaluation in rats

作　　者：杨伟培 梁中旭 蒋学华[1] 王凌[1] YANG Weipei;LIANG Zhongxu;JIANG Xuehua;WANG Ling(West China School of Pharmacy,Sichuan University,Chengdu,Sichuan,610041 P.R.China)

机构地区：[1]四川大学华西药学院,四川成都610041

出　　处：《华西药学杂志》2023年第5期526-529,共4页West China Journal of Pharmaceutical Sciences

摘　　要：目的 优化水飞蓟素-羟丙基-β-环糊精(SM-HP-β-CD)包合物的制备工艺,并考察其大鼠体内的药动学。方法 采用正交实验设计优化包合物的制备工艺,以包合率作为评价指标。运用LC-MS/MS法测定大鼠血浆中水飞蓟宾的浓度,并对其进行方法学验证。采用WinNonlin软件拟合水飞蓟宾的药动学参数。结果 SM-HP-β-CD包合物的最佳制备条件为:包合温度40℃,包合时间1 h, SM/HP-β-CD投料质量比1:12。包合物中水飞蓟宾的药动学参数Cmax为869.80±68.47 ng·mL-1、AUC0-∞为978.18±104.19 h·ng·mL-1、tmax为0.27±0.9 h;未包合组中水飞蓟宾的药动学参数Cmax为400.40±64.26 ng·mL-1、AUC0-∞为495.19±110.12 h·ng·mL-1,tmax为0.23±0.9 h。结论 经最佳工艺条件制得的包合物,其在大鼠体内的生物利用度较未包合组显著提高。OBJECTIVE To optimize the preparation process of silymarin-hydroxypropyl-β-cyclodextrin(SM-HP-β-CD)inclusion complex and investigate its pharmacokinetics in rats.METHODS An orthogonal experimental design was used to optimize the preparation process of the inclusion complex,and the inclusion rate was used as the evaluation index.The concentration of silybin in rat plasma was determined by LC-MS/MS and its methodology was validated.The pharmacokinetic parameters of silybin were calculated by WinNonlin software.RESULTS The optimal conditions for the preparation of SM-HP-β-CD inclusion complex were as follows:the inclusion temperature was at 40℃.The inclusion time was for 1 h and the mass ratio of SM to HP-β-CD was of 1∶12.The Cmax,AUC0-∞,and tmax of silybin in the inclusion complex were 869.80±68.47 ng·mL-1,978.18±104.19 h·ng·mL-1,and 0.27±0.9 h while the Cmax,AUC0-∞,and tmax of silybin in the free silymarin were 400.40±64.26 ng·mL-1,495.19±110.12 h·ng·mL-1,and 0.23±0.9 h.CONCLUSION Prepared by the optimal process conditions the bioavailability of the silybin inclusion complex in rats is significantly greater than of the free silymarin.

关 键 词：水飞蓟素 羟丙基-Β-环糊精 包合物 生物利用度 水飞蓟宾 饱和水溶液法 药动学 包合率 

分 类 号：R94[医药卫生—药剂学]