本文關(guān)鍵詞： 生物分配微乳液相色譜 DSA TS 藥動(dòng)學(xué) 定量保留-活性關(guān)系 中藥生物指紋圖譜　出處：《廣東藥學(xué)院》2014年碩士論文　論文類型：學(xué)位論文

【摘要】：目的 本課題以丹參為模型藥材，利用生物分配微乳液相色譜和定量保留-活性關(guān)系（QRAR）構(gòu)建中藥多組分藥動(dòng)學(xué)數(shù)據(jù)與色譜保留數(shù)據(jù)的關(guān)系模型，繪制反映丹參中多組分生物有效性的藥動(dòng)學(xué)指紋圖譜。 方法與結(jié)果 1、丹參主要活性成分在微乳液相體系中的保留研究 中藥中各主要成分在微乳系統(tǒng)中的分離是構(gòu)建中藥有效成分高通量篩選平臺(tái)、繪制中藥生物指紋圖譜的基礎(chǔ)。本實(shí)驗(yàn)考察了丹參藥材中9個(gè)水溶性和脂溶性成分在不同微乳體系中的保留情況。采用單因素實(shí)驗(yàn)，考察了微乳流動(dòng)相的pH、色譜柱的規(guī)格、表面活性劑的種類、油相種類以及添加劑（甲醇、β-環(huán)糊精、CB）對丹參成分保留的影響。 2、 DSA大鼠體內(nèi)藥動(dòng)學(xué)研究 本文用水提法提取丹參中總DSA，，并利用大孔樹脂進(jìn)行純化，濃縮后得到DSST。建立了測定DSST中SA1、SA4、SA5等組分含量的高效液相色譜方法。進(jìn)一步，建立用于測定大鼠血漿中各組分含量的高效液相色譜方法。以SD大鼠為實(shí)驗(yàn)對象，用DSST的混懸液進(jìn)行灌胃給藥，在給定的時(shí)間點(diǎn)從大鼠眼眶靜脈叢取血，測定血藥濃度，并利用3P97軟件包計(jì)算各組分的藥動(dòng)學(xué)參數(shù)。 3、 TS大鼠體內(nèi)藥動(dòng)學(xué)研究 本文用乙酸乙酯回流提取丹參中DTS，并建立測定DSZT中TS2和TS3含量的高效液相色譜方法。進(jìn)一步，建立用于測定大鼠血漿中TS含量的高效液相色譜方法。以SD大鼠為實(shí)驗(yàn)對象，用DSZT的混懸液進(jìn)行灌胃給藥，在給定的時(shí)間點(diǎn)從大鼠眼眶靜脈叢取血，測定血藥濃度，并利用3P97軟件包計(jì)算各組分的藥動(dòng)學(xué)參數(shù)。 4、定量保留-活性關(guān)系（QRAR）的構(gòu)建及丹參藥動(dòng)學(xué)指紋圖譜的繪制 選擇35個(gè)中藥成分作為模型藥物，考察不同微乳液相體系對其藥動(dòng)學(xué)參數(shù)的預(yù)測能力，篩選預(yù)測藥動(dòng)學(xué)參數(shù)的最優(yōu)體系。利用最優(yōu)微乳體系和支持向量機(jī)（SVM）回歸建立QRAR。以丹參中主要的水溶性和脂溶性成分作為測試集，對回歸模型的預(yù)測能力進(jìn)行驗(yàn)證。結(jié)果顯示模型具有良好的預(yù)測能力和穩(wěn)健性。最后，利用該QRAR模型繪制出丹參藥動(dòng)學(xué)指紋圖譜。
[Abstract]:Purpose. In this paper, using Danshen as a model medicinal material, using biodistribution microemulsion liquid chromatography and quantitative reserve-activity relationship (QRAR), the relationship model between multicomponent pharmacokinetic data and chromatographic retention data was established. The pharmacokinetic fingerprint was drawn to reflect the bioavailability of multiple components in Salvia miltiorrhiza. Methods and results. 1. Retention of main active components of Salvia miltiorrhiza in microemulsion system. The separation of the main components in the microemulsion system is to construct a high throughput screening platform for the active components of traditional Chinese medicine. In this paper, the retention of 9 water-soluble and fat-soluble components of Salvia miltiorrhiza in different microemulsion systems was investigated. The pH of mobile phase of microemulsion and the specification of chromatographic column were investigated by single factor experiment. Effects of surfactants, oil phase and additives (methanol, 尾-cyclodextrin CBB) on the retention of salvia miltiorrhiza (Salvia miltiorrhiza). In vivo pharmacokinetics of DSA rats. In this paper, the total DSAs from Salvia miltiorrhiza were extracted with water and purified by macroporous resin. A HPLC method for the determination of SA1SA4, SA5 and other components in DSST was established. A high performance liquid chromatography (HPLC) method was established for the determination of the contents of each component in rat plasma. SD rats were used as experimental objects. The suspension of DSST was administered intragastrically, and the blood samples were collected from the orbital venous plexus of rats at a given time point to determine the concentration of the drug. The pharmacokinetic parameters of each component were calculated by 3P97 software package. Pharmacokinetics of 3, TS rats in vivo. A high performance liquid chromatography (HPLC) method for the determination of TS2 and TS3 in DSZT was established by using ethyl acetate reflux to extract DTSs from salvia miltiorrhiza. Furthermore, a HPLC method for the determination of TS in rat plasma was established. The suspension of DSZT was used for intragastric administration. Blood samples were collected from the orbital venous plexus of rats at a given time point to determine the concentration of the drug. The pharmacokinetic parameters of each component were calculated by 3P97 software package. (4) Construction of quantitative retention activity relation (QRAR) and drawing of pharmacokinetic fingerprint of Salvia miltiorrhiza. Thirty-five components of traditional Chinese medicine were selected as model drugs to study the prediction ability of different microemulsion phase systems on pharmacokinetic parameters. The optimal system for predicting pharmacokinetic parameters was screened. The QRAR was established by using the optimal microemulsion system and support vector machine (SVM) regression. The main water-soluble and fat-soluble components of Salvia miltiorrhiza were used as test data. The prediction ability of the regression model is verified. The results show that the model has good predictive ability and robustness. Finally, the pharmacokinetic fingerprint of Salvia miltiorrhiza is drawn by using the QRAR model.
【學(xué)位授予單位】：廣東藥學(xué)院
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R96

【參考文獻(xiàn)】

相關(guān)期刊論文 前10條

1 袁淑蘭,王修杰;丹參酮抗腫瘤作用及其機(jī)理的研究[J];癌癥;2003年12期

2 湛月娥;徐江平;;丹酚酸B藥理作用的研究進(jìn)展[J];華南國防醫(yī)學(xué)雜志;2007年02期

3 孫進(jìn);王永軍;何仲貴;;生物分配色譜:高通量篩選藥物膜通透性和活性[J];化學(xué)進(jìn)展;2006年Z2期

4 于海波,徐長慶,單宏麗,董德利,楊寶峰,婁延平;丹參酮Ⅱ-A對大鼠心室肌細(xì)胞膜鉀電流的影響[J];哈爾濱醫(yī)科大學(xué)學(xué)報(bào);2002年02期

5 高霞;王著明;溫守儉;;不同水提醇沉法純化丹參總酚酸工藝的比較[J];吉林醫(yī)學(xué);2009年07期

6 劉國華,包宏,李文超;用MATLAB實(shí)現(xiàn)遺傳算法程序[J];計(jì)算機(jī)應(yīng)用研究;2001年08期

7 邊霞;米良;;遺傳算法理論及其應(yīng)用研究進(jìn)展[J];計(jì)算機(jī)應(yīng)用研究;2010年07期

8 周正武;丁同梅;田毅紅;王曉峰;;Matlab遺傳算法優(yōu)化工具箱(GAOT)的研究與應(yīng)用[J];機(jī)械研究與應(yīng)用;2006年06期

9 張文軍，包曉峰，王秀鳳，徐銘漁，錢振淮;丹參酮Ⅱa磺酸鈉抑制巨噬細(xì)胞源性生長因子刺激平滑肌細(xì)胞c－myc基因表達(dá)[J];中國動(dòng)脈硬化雜志;1996年01期

10 梅虎,梁桂兆,周原,李志良;支持向量機(jī)用于定量構(gòu)效關(guān)系建模的研究[J];科學(xué)通報(bào);2005年16期

本文編號(hào)：1520927