金合欢素纳米混悬剂的制备及其体内药动学研究  

Preparation and in vivo pharmacokinetics of acacetin nanosuspensions

作　　者：张佩琛 王涛[2] ZHANG Pei-chen;WANG Tao(Zhengzhou Shuqing Medical College,Zhengzhou 450064,China;Zhengzhou University,Zhengzhou 450001,China)

机构地区：[1]郑州澍青医学高等专科学校,河南郑州450064 [2]郑州大学,河南郑州450001

出　　处：《中成药》2022年第11期3415-3421,共7页Chinese Traditional Patent Medicine

基　　金：国家自然科学基金项目(81773175)。

摘　　要：目的制备金合欢素纳米混悬剂,并考察其体内药动学。方法高压均质法制备纳米混悬剂,测定粒径、Zeta电位、溶解度、体外溶出。以PVP K30占比、稳定剂用量、均质次数为影响因素,粒径为评价指标,Box-Behnken响应面法优化制备工艺。大鼠随机分为3组,分别灌胃给予金合欢素、物理混合物、金合欢素纳米混悬剂的0.5%CMC-Na混悬液(50 mg/kg),取血,HPLC-MS法测定金合欢素血药浓度,计算主要药动学参数。结果最佳条件为PVP K30占比47%,稳定剂用量215 mg,均质次数12次,粒径为214.7 nm,PDI为0.094,Zeta电位为-31.6 mV,溶解度提高至11.71倍,12 h内累积溶出度达95.82%。与原料药比较,纳米混悬剂t_(max)缩短(P<0.01),C_(max)、AUC_(0~t)、AUC_(0~∞)升高(P<0.01),相对生物利用度提高至5.18倍。结论纳米混悬剂可改善金合欢素溶解度和溶出度,促进药物吸收。AIM To prepare acacetin nanosuspensions and to investigate their in vivo pharmacokinetics.METHODS The nanosuspensions were prepared by high-pressure homogenization method,after which the particle size,Zeta potential,solubility and in vitro dissolution were determined.With PVP K30 proportion,stabilizer consumption and homogenization frequency as influencing factors,particle size as an evaluation index,the preparation process was optimized by Box-Behnken response surface method.Rats were randomly assigned into three groups and given intragastric administration of the 0.5%CMC-Na suspensions of acacetin,physical mixture and acacetin nanosuspensions(50 mg/kg),respectively,after which blood collection was made,HPLC-MS was adopted in the plasma concentration determination of acacetin,and main pharmacokinetic parameters were calculated.RESULTS The optimal conditions were 47%for PVP K30 proportion,215 mg for stabilizer consumption,and 12 times for homogenization frequency.The particle size,PDI and Zeta potential were 214.7 nm,0.094 and-31.6 mV,respectively,and the solubility was enhanced to 11.71 times with the accumulative dissolution rate within 12 h of 95.82%.Compared with raw medicine,the nanosuspensions demonstrated shortened t_(max)(P<0.01)and increased C_(max),AUC_(0-t),AUC_(0-∞)(P<0.01),and the relative bioavailability was elevated to 5.18 times.CONCLUSION Nanosuspensions can improve the solubility and dissolution rate of acacetin and promote drug absorption.

关 键 词：金合欢素 纳米混悬剂 制备 体内药动学 高压均质法 HPLC-MS 

分 类 号：R944[医药卫生—药剂学]