【作者】 王晴雯；

【导师】 李建军； 屈凌波；

【作者基本信息】 郑州大学 ， 药物分析学， 2011， 硕士

【摘要】 降压避风片是由黄芩,槐角,落花生枝叶,盐酸甲基左炔苄胺,氢氯噻嗪五味药物组成的一种新型的中西药合剂降压药,该药不仅降压平稳,而且具有软化和修复血管的功效,是一种可以长期服用的降压药。研究表明,降压避风片中富含的黄酮类成分以及盐酸甲基左炔苄胺,氢氯噻嗪是该药降压作用的主要活性成分,但部颁标准中仅将单一成分氢氯噻嗪作为该药质量控制的主要指标。建立降压避风片中多组分测定的方法体系和以多组分为指标的质量控制体系,是保证该药质量控制的有效途径。另外,降压避风片是一种以多活性成分为药效的一种药物,这些活性成分进入生物体内之后的药代动力学及组织分布研究对于我们了解该药的活性机制及安全性评价具有重要意义。目前关于该药质量控制及活性成分体内分析的研究缺乏报导。基于降压避风片药物质量控制及药物安全性评价方面存在的问题,我们进行了如下工作：一、降压避风片中盐酸甲基丙炔苄胺的毛细管电泳-电致化学发光法测定通过实验条件优化,首次建立了降压避风片中的盐酸甲基丙炔苄胺的毛细管电泳-电致化学发光测定方法,测定了其中盐酸甲基丙炔苄胺的含量。在最佳的实验条件下,盐酸甲基丙炔苄胺的线性范围为0.08～2.0mg/L,最低检测限为1.2μg/L(S/N=3)。对浓度为1.2 mg/L的盐酸甲基丙炔苄胺进行平行测定6次,得到峰高和迁移时间的RSD分别为1.5%、3.2%,可应用与降压避风片及其相关制剂中盐酸甲基丙炔苄胺的含量测定。该方法相对于文献报道的高效液相色谱方法,具有灵敏,快速,试样量少等优点,并且样品处理简单,不消耗有机试剂。二、高效液相色谱法测定大鼠血浆中的盐酸甲基丙炔苄胺在优化的色谱条件和血浆样品前处理条件下,建立了大鼠血浆中盐酸甲基丙炔苄胺的高效液相色谱测定方法,并对盐酸甲基丙炔苄胺在大鼠血浆中的药代动力学进行探讨。结果表明,大鼠体内的盐酸甲基丙炔苄胺含量在480min时达到最大,这与盐酸甲基丙炔苄胺的作用时间较慢相符合。盐酸甲基丙炔苄胺在大鼠体内的代谢呈现两室模型,主要的药代动力学参数为：Ka/h-1=88.097, T1/2a/h=3.343, T1/2β/h=3.663, Cmax/mg L-1=0.4983, AUC(0～t)/mg h L-1=4.523, AUC(0-∞)/mghL-1=5.501。这些数据对盐酸甲基丙炔苄胺的临床监测以及应用提供一定的参考。三、高效液相色谱法同时测定降压避风片中的八种活性成分通过优化色谱条件,建立了三波长-梯度洗脱高效液相色谱法同时测定降压避风片中八种活性成分。流动相为乙腈-0.05 mol/L磷酸二氢铵溶液(磷酸调pH值为2.8),线性洗脱梯度为：0min85%(B),12 min 78%(B),22 min 67%(B), 32 min 57%(B),流速：1.0 ml/min。在选定的色谱条件下,八种成分的R2均大于0.999,可以应用于降压避风片不同批次的测定。该方法对降压避风片的质量控制具有一定的参考意义。四、固相萃取-高效液相色谱法同时测定大鼠经灌胃降压避风片后血浆中的六种黄酮类化合物通过优化血浆样品的固相萃取方法,建立了降压避风片中的六种黄酮类化合物在大鼠血浆中含量测定的高效液相色谱分析方法,并对其的药代动力学进行了研究。结果表明,大鼠经灌胃0.5g降压避风片后六种黄酮类化合物在血浆中的C-T曲线呈现二室模型。从药代动力学参数可以看出,六种黄酮在大鼠体内的分布和消除较快,并且具有广泛的分布。该研究为临床应用和研究提供一定的参考。五、固相萃取-高效液相色谱法同时测定大鼠灌胃降压避风片后组织中的六种黄酮类化合物通过优化组织样品的固相萃取方法,建立了降压避风片中的六种黄酮类化合物在大鼠八处组织(心、肝、脾、肺、肾、脑、肠、胃)中含量测定的高效液相色谱分析方法,对降压避风片中的六种黄酮类化合物在大鼠组织中不同时间点的分布进行了研究。结果表明,大鼠经灌胃0.5g降压避风片后六种黄酮类化合物在胃肠道内即发生代谢、吸收。从药物在各组织中分布的浓度高低来看,黄酮类化合物主要经胃肠易化扩散吸收分布于胃肠道,并在肝、肾、心、肺、脾、肺、脑等各处组织都有一定分布。而黄酮苷类化合物比黄酮类化合物更易经过胃肠吸收。更多还原

【Abstract】 ’Jiangya Bifeng’tablet is a new kind of integrated traditional Chinese and Western medicine for the treatment of hypertension. However, up to now, only hydrochlorothiazide was chosen as index component for quality control of JYBF tablet. To date, determination of pargyline in’Jiangya Bifeng’tablet by high performance liquid chromatographic method has been reported, but other methods have not been reported. Determination of active ingredients of’Jiangya Bifeng’tablet and in vivo has not been reported. Studies are as follows:1. Determination of pargyline in’Jiangya Bifeng’tablet by CE-ECLBy optimizing the conditions of CE-ECL, CE-ECL determination of pargyline in ’Jiangya Bifeng’tablet was established based on the optimal sensitization of electrochemiluminescence of ruthenium terpyridine by pargyline. Under the optimimum system, the liner range of pargyline was 0.08-2.0 mg/L, the limit concentration of detection was 1.2μg/L (S/N=3). The RSD of peak height and migration time of 1.2 mg/L pargyline (n=6) was 1.5% and 3.2%, respectively. The study provides a reference for quality control of’Jiangya Bifeng’tablet and other preparations of pargyline.2. Determination of pargyline in rat serum by HPLCBy optimizing the conditions of HPLC, determination of pargyline in rat serum by HPLC as established. As was shown in the result, the concentration of pargyline in rats’serum reached the maximum at 480 min, the parmacokinetics of pargyline showed two-bedroom model and the main parameters were:Ka/h"1=88.097, T1/2α/h=3.343, T1/2β/h=3.663, Cmax/mg L-1=0.4983, AUC(O～t)/mg h L-1=4.523, AUC(0-co)/mg h L-1=5.501. The study provides a reference for parmacokinetics analysis of pargyline.3. Determination of eight active components in’Jiangya Bifeng’tablet by HPLCBy optimizing the conditions of HPLC, determination of eight active components in’Jiangya Bifeng’tablet by HPLC was established. The mobile phase was acetonitrile-0.05 mol/L ammonium dihydrogen phosphate (pH=2.8); the linear gradient elution was:0 min 85%(B),12 min 78%(B),22 min 67%(B),32 min 57% (B); the flow rate was:1.0 ml/min. The study provides a reference for quality control of’Jiangya Bifeng’tablet and other preparations of pargyline.4. Determination of six flavones in rat serum by HPLCBy optimizing the conditions of HPLC, determination of six flavones in rat serum by HPLC was established. As was shown in the result, the C-T profiles of the six flavones in rats’serum showed two-bedroom models after orally administrated 0.5 g ’Jiangya Bifeng’tablet. From the pharmacokinetic parameters, it was seen that the six flavones in rats distribut and eliminate fast, and have broad distributions. The study provides a reference for parmacokinetics analysis of six flavones in’Jiangya Bifeng’ tablet.5. Determination of six flavones in rat tissues by HPLCBy optimizing the conditions of HPLC, determination of six flavones in rat tissues by HPLC was established. As was shown in the result, the six flavones were widely distributed in eight tissues after orally administrated 0.5 g’Jiangya Bifeng’ tablet. From drug distribution in various tissues, the flavones facilitated diffusion through the gastrointestinal absorption and distribution in the gastrointestinal tract, and in the liver, kidney, heart, lung, spleen, lung, brain and other parts of organization. The study provides a reference for tissue distribution of six flavones in’Jiangya Bifeng’ tablet.更多还原