基于血清藥物化學技術的兩色金雞菊活性成分分析及藥代動力學研究
本文選題:兩色金雞菊 + 血清藥物化學; 參考:《新疆醫(yī)科大學》2017年碩士論文
【摘要】:目的:1.以大鼠為研究對象,觀察兩色金雞菊血清藥物化學成分變化。2.考察兩色金雞菊在人肝微粒體的體外代謝。3.研究兩色金雞菊在小鼠體內(nèi)的藥代動力學及組織分布。方法:1.建立兩色金雞菊高效液相(HPLC)指紋圖譜的基礎上,比較兩色金雞菊醇提物、空白血清及給藥血清的HPLC指紋圖譜,確定兩色金雞菊血中移行成分。2.將肝微粒體空白對照、兩色金雞菊醇提物乙醇溶液、滅活肝微粒體加兩色金雞菊醇提物及肝微粒體加兩色金雞菊醇提物進行體外共孵育,采用高效液相色譜、超高效液相色譜-串聯(lián)質(zhì)譜測定,通過對比色譜峰,闡明兩色金雞菊在肝微粒體的體外代謝規(guī)律。3.在建立HPLC測定大鼠血清及組織中黃諾馬苷、馬里苷濃度方法的基礎上,小鼠灌胃給予兩色金雞菊醇提物,用HPLC檢測各時間點血清及組織中藥物濃度,并用藥動學程序PK solution 2.0 TM(Summit Research Services,USA)進行分析。結(jié)果:1.在兩色金雞菊含藥血清中發(fā)現(xiàn)了7種入血成分,其中6種為原型成分,1種為代謝產(chǎn)物。2.兩色金雞菊醇提物在人肝微粒體藥物代謝酶作用下,各成分含量均降低,其中四4種物質(zhì)被代謝而未被檢出,分別為黃酮奧卡寧(Flavanokanin)、3,4’,5,6,7-pentahydroxyflavanone、橙酮金雞菊苷(Maritimein)、馬里苷(Marein)、奧卡寧(Okanin)。3.小鼠灌胃給藥兩色金雞菊醇提物后,黃諾馬苷主要藥動學參數(shù):達峰時間Tmax、峰濃度Cmax、半衰期T1/2、藥時曲線下面積AUC、血清清除CL分別為5.667h、223.648μg/m L、4.309h、2293.727μg-hr/mL、49218.246mL/hr/kg;馬里苷主要藥動學參數(shù):達峰時間Tmax、峰濃度Cmax、半衰期T1/2、藥時曲線下面積AUC、血清清除CL分別為5.000h、112.683μg/mL、4.419h、1350.050μg-hr/m L、82957.857m L/hr/kg。結(jié)論:1.7種入血成分可能是兩色金雞菊的體內(nèi)直接作用物質(zhì),對其進行更深入的研究有助于探索其藥效物質(zhì)基礎及作用機制。2.兩色金雞菊醇提物在人肝微粒體藥物代謝酶作用下可較快地代謝消除。3.分別獲得黃諾馬苷、馬里苷的藥代動力學參數(shù),且黃諾馬苷主要分布在肝、腎組織中。
[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.
【學位授予單位】:新疆醫(yī)科大學
【學位級別】:碩士
【學位授予年份】:2017
【分類號】:R284;R285.5
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