中国中药杂志

2015, v.40(12) 2428-2434

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补肾通络方中马钱苷、阿魏酸和二苯乙烯苷的体内药代动力学研究
Pharmacokinetics of loganin,ferulic acid and stilbene glucoside in Bushen Tongluo formula in vivo

刘湘丹;黄攀;卢岳华;马铭;周日宝;袁林祥;彭新君;
LIU Xiang-dan;HUANG Pan;LU Yue-hua;MA Ming;ZHOU Ri-bao;YUAN Lin-xiang;PENG Xin-jun;School of Pharmacy,Hunan University of Chinese Medicine;School of Chemistry and Chemical Engineering,Hunan Normal University,Key Laboratory of Chemicobiology and Traditional Chinese Medicine analysis under Ministry of Education;School of Medicine,Hunan Normal University;

摘要(Abstract):

研究灌胃补肾通络方后大鼠血浆中马钱苷、阿魏酸和二苯乙烯苷药代动力学特征。采用液-液萃取法处理血浆样品;HPLC-UV检测含量,色谱柱为Johnson spherigel C18(4.6 mm×250 mm,5μm),流动相为甲醇-0.01%冰醋酸水溶液,梯度洗脱,流速为1 m L·min-1,柱温为30℃,检测波长:马钱苷为235 nm,阿魏酸和二苯乙烯苷为320 nm,进样量为10μL。采用DAS 2.0软件对所测数据进行处理,得到大鼠血浆中马钱苷、阿魏酸和二苯乙烯苷的主要药动学参数如下:Cmax分别为(0.369±0.042),(0.387±0.071),(0.233±0.044)mg·L-1;tmax分别为(0.226±0.022),(0.282±0.031),(0.233±0.044)h;t1/2β分别为(6.89±0.20),(10.7±0.11),(6.93±0.090)h;AUC0-∞分别为(1.91±0.36),(3.22±0.52),(1.52±0.33)mg·h·L-1;AUC0-t分别为(1.62±0.33),(2.58±0.43),(1.30±0.30)mg·h·L-1;CL分别为(20.2±4.0),(1.39±0.23),(31.7±6.9)L·h-1·kg-1。药代动力学研究结果表明,灌胃补肾通络方后马钱苷、阿魏酸和二苯乙烯苷药动学曲线均符合血管外给药二室模型,且3种成分吸收快,马钱苷和二苯乙烯苷消除速度中等,阿魏酸消除慢(但生物利用度为最高),每天给药3次能维持血药浓度,适合制成普通口服制剂。
To study the pharmacokinetics characteristic of loganin,ferulic acid and stilbene glucoside in rat plasma after oral administration of Bushen Tongluo formula. The plasma samples were treated by using liquid-liquid extraction technique,the concentrations were determined by HPLC-UV. Johnson spherigel C18column(4. 6 mm × 250 mm,5 μm) was adopted and eluted with the of mobile phase of methanol-water containing 0. 01% glacial acetic acid in a gradient mode,with the flow rate at 1. 0 m L·min- 1,column temperature at 30 ℃ and injection volume of 10 μL. According to the findings,loganin was determined at 235 nm,ferulic acid and stilbene glucoside were determined at 320 nm,with the sample size of 10 μL. The pharmacokinetic parameters of loganin,ferulic acid and stilbene glucoside were calculated by DAS 2. 0 software as follows: Cmaxwas(0. 369 ± 0. 042),(0. 387 ± 0. 071),(0. 233 ±0. 044) mg·L- 1; tmaxwas(0. 226 ± 0. 022),(0. 282 ± 0. 031),(0. 233 ± 0. 044) h; t1 /2βwas(6. 89 ± 0. 20),(10. 73 ± 0. 11),(6. 93 ± 0. 09) h; AUC0-∞was(1. 91 ± 0. 36),(3. 22 ± 0. 52),(1. 52 ± 0. 33) mg·h·L- 1; AUC0-twas(1. 62 ± 0. 33),(2. 58 ±0. 43),(1. 30 ± 0. 30) mg·h·L- 1; CL was(20. 2 ± 4. 0),(1. 39 ± 0. 23),(31. 7 ± 6. 9) L·h- 1·kg- 1,respectively. The results showed that after the oral administration with Bushen Tongluo formula,loganin,ferulic acid and stilbene glucoside showed concentration-time curves in conformity with the two compartment model,with a rapid absorption,loganin and stilbene glucoside was excreted at a moderate speed,and ferulic acid was excreted slowly( but with the highest bioavailability). Bushen Tongluo formula can main maintain plasma concentration with three administrations everyday and so is suitable to be made into common oral preparation.

关键词(KeyWords): 补肾通络方;马钱苷;阿魏酸;二苯乙烯苷;药代动力学
Bushen Tongluo formula;loganin;ferulic acid;stilbene glucoside;pharmacokinetic

Abstract:

Keywords:

基金项目(Foundation): 湖南省教育厅/财政厅重点项目(12A098);; 湖南省教育厅大学生创新项目(2013-176);; 湖南中医药大学优秀教师培养项目(2013);; 湖南省“中药学”重点学科建设项目(湘教通[2011]76号);; 国家中医药管理局“药用植物学”重点学科项目(国中医药发[2009]30号)

作者(Author): 刘湘丹;黄攀;卢岳华;马铭;周日宝;袁林祥;彭新君;
LIU Xiang-dan;HUANG Pan;LU Yue-hua;MA Ming;ZHOU Ri-bao;YUAN Lin-xiang;PENG Xin-jun;School of Pharmacy,Hunan University of Chinese Medicine;School of Chemistry and Chemical Engineering,Hunan Normal University,Key Laboratory of Chemicobiology and Traditional Chinese Medicine analysis under Ministry of Education;School of Medicine,Hunan Normal University;

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