基于血清药物化学技术的两色金鸡菊活性成分分析及药代动力学研究

发布时间：2018-04-14 07:41

本文选题：两色金鸡菊 + 血清药物化学　；参考：《新疆医科大学》2017年硕士论文

【摘要】：目的:1.以大鼠为研究对象,观察两色金鸡菊血清药物化学成分变化。2.考察两色金鸡菊在人肝微粒体的体外代谢。3.研究两色金鸡菊在小鼠体内的药代动力学及组织分布。方法:1.建立两色金鸡菊高效液相(HPLC)指纹图谱的基础上,比较两色金鸡菊醇提物、空白血清及给药血清的HPLC指纹图谱,确定两色金鸡菊血中移行成分。2.将肝微粒体空白对照、两色金鸡菊醇提物乙醇溶液、灭活肝微粒体加两色金鸡菊醇提物及肝微粒体加两色金鸡菊醇提物进行体外共孵育,采用高效液相色谱、超高效液相色谱-串联质谱测定,通过对比色谱峰,阐明两色金鸡菊在肝微粒体的体外代谢规律。3.在建立HPLC测定大鼠血清及组织中黄诺马苷、马里苷浓度方法的基础上,小鼠灌胃给予两色金鸡菊醇提物,用HPLC检测各时间点血清及组织中药物浓度,并用药动学程序PK solution 2.0 TM(Summit Research Services,USA)进行分析。结果:1.在两色金鸡菊含药血清中发现了7种入血成分,其中6种为原型成分,1种为代谢产物。2.两色金鸡菊醇提物在人肝微粒体药物代谢酶作用下,各成分含量均降低,其中四4种物质被代谢而未被检出,分别为黄酮奥卡宁(Flavanokanin)、3,4’,5,6,7-pentahydroxyflavanone、橙酮金鸡菊苷(Maritimein)、马里苷(Marein)、奥卡宁(Okanin)。3.小鼠灌胃给药两色金鸡菊醇提物后,黄诺马苷主要药动学参数:达峰时间Tmax、峰浓度Cmax、半衰期T1/2、药时曲线下面积AUC、血清清除CL分别为5.667h、223.648μg/m L、4.309h、2293.727μg-hr/mL、49218.246mL/hr/kg;马里苷主要药动学参数:达峰时间Tmax、峰浓度Cmax、半衰期T1/2、药时曲线下面积AUC、血清清除CL分别为5.000h、112.683μg/mL、4.419h、1350.050μg-hr/m L、82957.857m L/hr/kg。结论:1.7种入血成分可能是两色金鸡菊的体内直接作用物质,对其进行更深入的研究有助于探索其药效物质基础及作用机制。2.两色金鸡菊醇提物在人肝微粒体药物代谢酶作用下可较快地代谢消除。3.分别获得黄诺马苷、马里苷的药代动力学参数,且黄诺马苷主要分布在肝、肾组织中。
[Abstract]:Purpose 1.In this study, the changes of serum chemical constituents of two-color golden chrysanthemum were observed in rats. 2. 2.The in vitro metabolism of chrysanthemum bicolor in human liver microsomes was investigated.The pharmacokinetics and tissue distribution of chrysanthemum bicolor in mice were studied.Method 1: 1.On the basis of establishing two color high performance liquid phase (HPLC) fingerprint, the HPLC fingerprint of the alcohol extract, blank serum and administration serum were compared, and the migrating components. 2. 2 in the blood of the two color chrysanthemum chrysanthemum were determined.Liver microsomes were incubated in vitro with ethanol solution, inactivated liver microsomes and dichromatic chrysanthemum alcohol extracts, and liver microsomes with dichromatic chrysanthemum alcohol extracts. High performance liquid chromatography (HPLC) was used.Ultrahigh performance liquid chromatography-tandem mass spectrometry (HPLC-MS) was used to elucidate the in vitro metabolism of the dichromatic chrysanthemum in liver microsomes by contrasting the chromatographic peaks.On the basis of establishing a HPLC method to determine the concentration of flavanoside and Marinoside in serum and tissue of rats, mice were given dichromatid alcohol extract by gavage, and serum and tissue drug concentrations were detected by HPLC at different time points.The pharmacokinetic program was analyzed by solution 2.0 TM(Summit Research Services.The result is 1: 1.Seven kinds of blood entry components were found in the serum containing two colors of Chrysanthemum chinensis, of which 6 were prototypes and 1 was metabolite. 2.Under the action of human liver microsomal drug metabolizing enzyme, the contents of each component of the ethanol extract of two color chrysanthemum decreased, four of which were metabolized but not detected, namely Flavaninine Flavanokaninanine (Flavanokanintii), Flavanokaninine (Flavananine), Flavananine Flavanone (Flavananine), Flavananine Flavananine (Flavananine), Flavananine Flavananine (Flavananine), Flavananine (Flavananine), Flavananine (Flavananine),Mice were treated with alcohol extract of dichromatic chrysanthemum by gavage.Under the line area AUC, serum clearance CL was 112.683 渭 g / mL ~ (-1) 4.419 渭 g-hr/m / L ~ (13) 50.050 渭 g-hr/m / L ~ (-1) 2957.857 m / L ~ (-1 / kg) 路ml ~ (-1) 路ml ~ (-1) 路mL ~ (-1) 路L ~ (-1).Conclusion 1. 7 species of blood entry components may be the direct acting substances in the body of Trifolium bicolor, and further study on them will be helpful to explore the substance basis and mechanism of its pharmacodynamics.Under the action of human liver microsomal drug metabolizing enzyme, the ethanol extract of dichromous chrysanthemum could be quickly metabolized and eliminated. 3.The pharmacokinetic parameters of flavanoside and marinoside were obtained, and they were mainly distributed in liver and kidney.
【学位授予单位】：新疆医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R284;R285.5

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