粒子设计对参苓白术散在大鼠体内药动学过程的影响  

Effect of particle design on pharmacokinetics of Shenling Baizhu Pulvis in rats

作　　者：周晓 李婧琳 邹俊波 张小飞[1] 郭东艳[1] 程江雪[1] 史亚军[1] 石心红[2] 贾晓斌 ZHOU Xiao;LI Jing-lin;ZOU Jun-bo;ZHANG Xiao-fei;GUO Dong-yan;CHENG Jiang-xue;SHI Ya-jun;SHI Xin-hong;JIA Xiao-bin(School of Pharmacy,Shaanxi University of Chinese Medicine,Xianyang 712046,China;China Pharmaceutical University,Nanjing 211198,China)

机构地区：[1]陕西中医药大学药学院,陕西咸阳712046 [2]中国药科大学,江苏南京211198

出　　处：《中草药》2020年第19期4925-4933,共9页Chinese Traditional and Herbal Drugs

基　　金：国家重点研发计划(2018YFC1706904);陕西省自然科学基础研究项目(2018JM7157);陕西省中医药管理局中药制药工程重点学科项目(2017[A2]);陕西中医药大学学科创新团队项目(2019-YL11)。

摘　　要：目的借助LC-MS探讨参苓白术散经粒子设计改性后在大鼠体内的药动学过程。方法采用粒子设计技术制备参苓白术粒子设计散。建立科学可行的LC-MS分析方法,对给药后不同时间点大鼠血浆中人参皂苷Re(GI-Re)、人参皂苷Rb1(GI-Rb1)、人参皂苷Rg1(GI-Rg1)、白术内酯I(AT-I)、白术内酯II(AT-II)、茯苓酸(PA)指标成分的血药浓度进行测定,并采用DAS 3.2.8药动学软件对数据进行智能化分析,选择非房室模式对药动学参数进行统计。结果建立的LC-MS分析方法对大鼠血浆中的指标性成分均具有良好的线性关系和专属性,且精密度、准确度、提取回收率的RSD值均小于5%,稳定性的RSD值小于10%。给药后粒子设计散中指标成分GI-Re、GI-Rb1、GI-Rg1、AT-I、AT-II、PA的达峰浓度(Cmax)、药时曲线下面积(AUC0~∞)较普通散均有不同程度的增加,AUC0~∞分别为改性前的1.52、2.02、1.22、1.41、1.13、1.43倍。结论LC-MS分析方法符合《中国药典》生物样品分析要求,参苓白术散经粒子设计改性后在体内的吸收速度变快,生物利用度提高。Objective Using LC-MS to explore the pharmacokinetic process in rats of Shenling Baizhu Pulvis(SBP), which was modified by particle design technology. Methods Particle design powder of SBP was prepared by particle design technology. A scientific and feasible LC-MS analysis method was established to determine the blood concentration of index compounds such as ginsenoside Re(GI-Re), ginsenoside Rb1(GI-Rb1), ginsenoside Rg1(GI-Rg1), atractylenolide I(AT-I), atractylenolide II(AT-II) and pachymic acid(PA) in rats at different time points after administration. DAS 3.2.8 pharmacokinetic software was adopted to analyze the data, which related to blood concentration of index compounds, and the pharmacokinetics parameters were calculated by the non-compartmental model. Results LC-MS analysis method was established, which has a good linear relationship and specificity for the index compounds in rats, and the RSD of precision, accuracy, extraction recovery and stability were all less than 5% or 10%. Compared with ordinary powder, the particle design powder displayed increased Cmax and AUC0—∞ after administration, and the AUC0—∞ of GI-Re, GI-Rb1, GI-Rg1, AT-I, AT-II and PA were increased to 1.52, 2.02, 1.22, 1.41, 1.13 and 1.43 times, respectively. Conclusion The LC-MS analysis method meet the requirements of biological sample analysis in Pharmacopoeia of the People’s Republic of China. After particle design and modification, the absorption speed of SBP in vivo become faster and the bioavailability is improved significantly.

关 键 词：参苓白术散 粒子设计 改性 LC-MS 药动学 生物利用度 人参皂苷RE 人参皂苷Rb1 人参皂苷Rg1 白术内酯I 白术内酯II 茯苓酸 

分 类 号：R283.6[医药卫生—中药学]