中药复方药物动力学总量统计矩法的实验验证研究  

Experimental studies on pharmacokinetics of three components in Buyanghuanwu injection on base of total quantum statistical moment

作　　者：贺福元[1,2,3] 邓凯文[4] 刘文龙[1] 石继连[1] 伍勇[1] 刘伟[1] 贺庆平[1] 李博[1] 

机构地区：[1]湖南中医药大学药学院,湖南长沙410208 [2]中药药性与药效国家中医药管理局重点实验室,湖南长沙410208 [3]湖南中医药大学现代中药制技术与评价实验室,湖南长沙410208 [4]湖南中医药大学第一附属医院,湖南长沙410007

出　　处：《中国中药杂志》2013年第2期253-262,共10页China Journal of Chinese Materia Medica

基　　金：国家自然科学基金项目(81073142;30901971);湖南省自然科学基金重点项目(11JJ2055);湖南省教育厅"十二五"药学重点学科项目

摘　　要：目的:对已建立的药物动力学总量统计矩法用补阳还五汤中黄芪甲苷、芍药苷、川芎嗪3个成分进行验证,建立中药复方多成分体系的药物动力学实验方法。方法:采用反相高效液相色谱法测定,其条件为C18色谱柱(4.6 mm×250 mm,5μm);黄芪甲苷ELSD测定;流动相乙腈-1%乙酸溶液(35∶65),流速1 mL·min-1;柱压(15.0±0.408)MPa;温度30℃;芍药苷、川芎嗪的检测波长254 nm,流动相甲醇-水(33∶67),流速1 mL·min-1;柱压(20.71±0.42)MPa。单个成分房室模型药物动力学参数采用DAS软件处理,总量统计矩按公式计算。结果:3个单成分在大鼠体内药物动力学都遵循二室模型(P<0.01),与叠加总浓度比,单个成分各参数相差最大上万倍,而总量统计矩参数的RSD为3.5%,3个成分药物动力学的总量统计矩参数AUCt(119.8±27.20)g.min·L-1;MRTt(210.0±54.49)min;VRTt(5.608±2.723)×104 min2;CLt为(0.319 6±0.068 8)mL·min-1·kg-1;Vt为(64.12±8.243)mL·kg-1;t0.95t为(588.9±149.4)min。这就说明3个成分总量的半衰期为(145.5±37.76)min,3药在0～674.2 min内代谢95%的浓度。结论:中药复方多成分药物动力学可采用总量统计矩法进行研究,该法能表征多成分体系总量的量-时变化的动力学规律。Objective ： To verify established the total quantum statistic moments model with astragaloside IV, paeonifiorin, tet- ramethylpyrazine in Buyanghuanwn injection, in order to establish a pharmacokinetic experimental method with multi-component tradi- tional Chinese medicine（ TCM ） compound system. Method： The RP-HPLC was adopted, with the chromatographic column of Cl8, 4. 6 mm × 250 mm, 5 μm. As for astragaloside IV, the ELSD detector was adopted with acetonitrile-water（ 35：65 ） as the mobile phase at 1 mL · min^-1 ; the pressure of column was （ 15.0 ±0. 408） MPa, the column temperature was 30 ℃. Regarding paeoniflorin and tetramethylpyrazine, the detection of wavelengths was 254 nm, with acetonitrile-water （ 35 ： 65 ） as the mobile phase at 1 mL · min^-1 , the column pressure of （15. 17 ± 0.41 ） MPa. The pharmacokinetic parameters for single component were dealt with DAS and the total quantum statistical moment（TQSM） parameters were calculated using formulations. Result： All of the three components followed the two compartmental pharkacokinetic model （P 〈 0. 01 ） in rats. Compared with the superimposed total concentration, each single compo- nent showed difference in parameters up to 10 000 times at most, whereas the RSD of TQSM parameters was 3. 510%. The TQSM pharmacokinetic parameters of the three components in Buyanghuanwu injection showed that AUC,, MRTt, VRT,, CLt, Vt were （119.8±27.20） g·min· L^-1, （210.0±54.49） min, （5.608±2.723） ×104min2, （0.3196±0.0688） mL·min^-1·kg^-1 and （64. 12 ±8.243） mL·kg^-1 , respectively, suggesting that the half-life time for the three components were （145.5 ±37.76） rain and 95% of them were metabolized within 0-674. 2 min. Conclusion： The TQSM can be used to study pharmacokinetic parameters of multi-component TCM compound, because the method can characterize the pharmacokinetic regularity of quantum-time change in a multi-component system.

关 键 词：总量统计矩 药物动力学 谱动学 补阳还五汤 黄芪甲苷 芍药苷 川芎嗪 

分 类 号：R285[医药卫生—中药学]