葛根与复方脑脉通给药后大豆苷元在大鼠体内的药动学比较
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摘要
目的:比较复方脑脉通和葛根药材提取物中大豆苷元在大鼠体内的药代动力学参数,评价复方脑脉通提取物中其他成分对大豆苷元药动学的影响。方法:将12只大鼠随机分成2组,按大豆苷元1.002 5 mg·kg-1分别灌胃给予复方脑脉通提取物和葛根提取物,不同时间点采血后进行UPLC-MS分析,测定血浆中大豆苷元浓度,采用DAS 2.0软件计算主要药动学参数,通过SPSS 16.0软件对不同药动学参数进行单因素方差分析。结果:大豆苷元线性范围6.175~741.0μg·L-1,定量限6.175μg·L-1,最低检测限1.235μg·L-1。复方脑脉通和葛根药材提取物中大豆苷元的达峰浓度和清除速率有显著性差异,其他参数则均无显著性差异。结论:建立的UPLC-MS专属性强、准确、灵敏,适用于以大豆苷元为主要成分的药物的体内血药浓度测定。复方脑脉通中其他药材对大豆苷元的吸收及清除有较大影响,使大豆苷元的达峰浓度及清除速率降低。
Objective: To establish an UPLC-MS method for determining the content of daidzein in rat plasma,and compare pharmacokinetic parameters of daidzein in rats after gavage of compound Naomaitong and Puerariae Lobatae Radix extract for evaluating effects of other ingredients in compound Naomaitong extract on pharmacokinetics of daidzein. Method: Twelve rats were randomly divided into two groups, gastric gavage of compound Naomaitong and Puerariae Lobatae Radix extract according to 1. 002 5 mg·kg- 1of daidzein,plasma samples collected at different time, and then using UPLC-MS to determine plasma concentrations of daidzein,pharmacokinetic parameters were calculated by DAS 2. 0 software,and its one-way ANOVA with SPSS 16. 0 software.Result: There was a good linearity over concentration ranges of 6. 175-741. 0 μg·L- 1,limit of quantitation was6. 175 μg ·L- 1,the lowest detection limit was 1. 235 μg ·L- 1. Cmaxand CL / F of daidzein from compound Naomaitong and Puerariae Lobatae Radix extract were significantly different, the other parameters were not significantly different. Conclusion: This UPLC-MS is sensitive,accurate,specific and applicable to determine in vivo plasma concentration of drug with daidzein as a main ingredient. Other ingredients in compound Naomaitong extract have a great impact on absorption and removal of daidzein,so that Cmaxand CL / F of daidzein decrease.
Objective: To establish an UPLC-MS method for determining the content of daidzein in rat plasma,and compare pharmacokinetic parameters of daidzein in rats after gavage of compound Naomaitong and Puerariae Lobatae Radix extract for evaluating effects of other ingredients in compound Naomaitong extract on pharmacokinetics of daidzein. Method: Twelve rats were randomly divided into two groups, gastric gavage of compound Naomaitong and Puerariae Lobatae Radix extract according to 1. 002 5 mg·kg- 1of daidzein,plasma samples collected at different time, and then using UPLC-MS to determine plasma concentrations of daidzein,pharmacokinetic parameters were calculated by DAS 2. 0 software,and its one-way ANOVA with SPSS 16. 0 software.Result: There was a good linearity over concentration ranges of 6. 175-741. 0 μg·L- 1,limit of quantitation was6. 175 μg ·L- 1,the lowest detection limit was 1. 235 μg ·L- 1. Cmaxand CL / F of daidzein from compound Naomaitong and Puerariae Lobatae Radix extract were significantly different, the other parameters were not significantly different. Conclusion: This UPLC-MS is sensitive,accurate,specific and applicable to determine in vivo plasma concentration of drug with daidzein as a main ingredient. Other ingredients in compound Naomaitong extract have a great impact on absorption and removal of daidzein,so that Cmaxand CL / F of daidzein decrease.
引文
[1]韩旭,刘黎青.中医药治疗脑卒中的研究进展[J].中医药信息,2014,7(31):193-195.
[2]林森.缺血性中风的中西医治疗研究进展[J].中医药导报,2011,17(3):119-121.
[3]王明航,李建生,刘轲,等.脑脉通对老龄大鼠脑缺血再灌注血-脑脊液屏障损伤的保护作用[J].中国老年学杂志,2006,26(9):1211-1212.
[4]任小巧,李建生.脑脉通对老龄大鼠脑缺血/再灌注损伤脑保护作用的研究[J].中国中药杂志,2004,29(1):66-69.
[5]李建生,刘敬霞,张新峰,等.脑脉通对骨髓干细胞动员保护大鼠脑缺血损伤的影响[J].中国老年学杂志,2010,7(30):1832-1836.
[6]韩静,王伟,王绿娅,等.葛根素与大豆苷元对血管平滑肌细胞增殖的抑制作用[J].中国中药杂志,2004,29(5):437-440.
[7]李培恒,王继峰,牛建昭,等.染料木素和大豆苷元对去卵巢大鼠甘油三酯代谢的作用[J].中国药理学通报,2004,20(1):72-74.
[8]李湘辉,张金超,肖培根,等.豆异黄酮类防治骨质疏松的作用机制[J].国外医药·植物药分册,2006,21(1):1-5.
[9]钟声,李泽玲,钟星明,等.大豆苷元对异丙肾上腺素所致心肌肥厚与抗氧化的影响[J].中国实验方剂学杂志,2013,19(9):204-206.
[10]周晓霞.葛根、粉葛药材中大豆苷元含量的测定[J].时珍国医国药,2012,23(11):2732-2734.
[11]周红英,王建华,闫凤云.RP-HPLC分离测定甘葛藤茎叶中葛根素、大豆苷和大豆苷元的含量[J].中国中药杂志,2007,32(10):937-939.
[12]白永涛,文红梅,周华,等.UPLC法测定大鼠血浆中大豆苷元浓度及药代动力学研究[J].中国药理学通报,2010,26(11):1512-1515.
[13]师永晶,王荣顺.大豆苷元固体分散体在小鼠体内的药动学研究[J].北方药学,2014,11(4):82.
[14]李力,翟学佳,陈东生.通脉方中葛根素和大豆苷元在大鼠体内药动学研究[J].中国医院药学杂志,2009,29(15):1258-1261.
[15]国海东,上官新晨,尹忠平.葛根异黄酮提取工艺研究[J].工艺技术,2014,35(6):87-90.
[16]梁丽谊,王汝上.葛根总黄酮提取工艺优化研究[J].今日药学,2014,24(12):866-872.
[17]杨帆,王淑美,林捷欣.葛根总黄酮提取工艺的考察[J].中国中医药现代远程教育,2014,12(3):156-157.
[18]田顺亮,钱学华.大鼠断尾取血固定装置的设计及取血的方法[J].中国比较医学杂志,2006,16(7):419-421.
[19]李侠,李绍平.实验大鼠连续断尾取血法的报告[J].医学综述,2007,13(24):2046.
[2]林森.缺血性中风的中西医治疗研究进展[J].中医药导报,2011,17(3):119-121.
[3]王明航,李建生,刘轲,等.脑脉通对老龄大鼠脑缺血再灌注血-脑脊液屏障损伤的保护作用[J].中国老年学杂志,2006,26(9):1211-1212.
[4]任小巧,李建生.脑脉通对老龄大鼠脑缺血/再灌注损伤脑保护作用的研究[J].中国中药杂志,2004,29(1):66-69.
[5]李建生,刘敬霞,张新峰,等.脑脉通对骨髓干细胞动员保护大鼠脑缺血损伤的影响[J].中国老年学杂志,2010,7(30):1832-1836.
[6]韩静,王伟,王绿娅,等.葛根素与大豆苷元对血管平滑肌细胞增殖的抑制作用[J].中国中药杂志,2004,29(5):437-440.
[7]李培恒,王继峰,牛建昭,等.染料木素和大豆苷元对去卵巢大鼠甘油三酯代谢的作用[J].中国药理学通报,2004,20(1):72-74.
[8]李湘辉,张金超,肖培根,等.豆异黄酮类防治骨质疏松的作用机制[J].国外医药·植物药分册,2006,21(1):1-5.
[9]钟声,李泽玲,钟星明,等.大豆苷元对异丙肾上腺素所致心肌肥厚与抗氧化的影响[J].中国实验方剂学杂志,2013,19(9):204-206.
[10]周晓霞.葛根、粉葛药材中大豆苷元含量的测定[J].时珍国医国药,2012,23(11):2732-2734.
[11]周红英,王建华,闫凤云.RP-HPLC分离测定甘葛藤茎叶中葛根素、大豆苷和大豆苷元的含量[J].中国中药杂志,2007,32(10):937-939.
[12]白永涛,文红梅,周华,等.UPLC法测定大鼠血浆中大豆苷元浓度及药代动力学研究[J].中国药理学通报,2010,26(11):1512-1515.
[13]师永晶,王荣顺.大豆苷元固体分散体在小鼠体内的药动学研究[J].北方药学,2014,11(4):82.
[14]李力,翟学佳,陈东生.通脉方中葛根素和大豆苷元在大鼠体内药动学研究[J].中国医院药学杂志,2009,29(15):1258-1261.
[15]国海东,上官新晨,尹忠平.葛根异黄酮提取工艺研究[J].工艺技术,2014,35(6):87-90.
[16]梁丽谊,王汝上.葛根总黄酮提取工艺优化研究[J].今日药学,2014,24(12):866-872.
[17]杨帆,王淑美,林捷欣.葛根总黄酮提取工艺的考察[J].中国中医药现代远程教育,2014,12(3):156-157.
[18]田顺亮,钱学华.大鼠断尾取血固定装置的设计及取血的方法[J].中国比较医学杂志,2006,16(7):419-421.
[19]李侠,李绍平.实验大鼠连续断尾取血法的报告[J].医学综述,2007,13(24):2046.