生物分配微乳液相色谱构建丹参药动学指纹图谱的研究

发布时间：2018-02-21 03:58

本文关键词： 生物分配微乳液相色谱 DSA TS 药动学定量保留-活性关系中药生物指纹图谱　出处：《广东药学院》2014年硕士论文　论文类型：学位论文

【摘要】：目的本课题以丹参为模型药材，利用生物分配微乳液相色谱和定量保留-活性关系（QRAR）构建中药多组分药动学数据与色谱保留数据的关系模型，绘制反映丹参中多组分生物有效性的药动学指纹图谱。方法与结果 1、丹参主要活性成分在微乳液相体系中的保留研究中药中各主要成分在微乳系统中的分离是构建中药有效成分高通量筛选平台、绘制中药生物指纹图谱的基础。本实验考察了丹参药材中9个水溶性和脂溶性成分在不同微乳体系中的保留情况。采用单因素实验，考察了微乳流动相的pH、色谱柱的规格、表面活性剂的种类、油相种类以及添加剂（甲醇、β-环糊精、CB）对丹参成分保留的影响。 2、 DSA大鼠体内药动学研究本文用水提法提取丹参中总DSA，，并利用大孔树脂进行纯化，浓缩后得到DSST。建立了测定DSST中SA1、SA4、SA5等组分含量的高效液相色谱方法。进一步，建立用于测定大鼠血浆中各组分含量的高效液相色谱方法。以SD大鼠为实验对象，用DSST的混悬液进行灌胃给药，在给定的时间点从大鼠眼眶静脉丛取血，测定血药浓度，并利用3P97软件包计算各组分的药动学参数。 3、 TS大鼠体内药动学研究本文用乙酸乙酯回流提取丹参中DTS，并建立测定DSZT中TS2和TS3含量的高效液相色谱方法。进一步，建立用于测定大鼠血浆中TS含量的高效液相色谱方法。以SD大鼠为实验对象，用DSZT的混悬液进行灌胃给药，在给定的时间点从大鼠眼眶静脉丛取血，测定血药浓度，并利用3P97软件包计算各组分的药动学参数。 4、定量保留-活性关系（QRAR）的构建及丹参药动学指纹图谱的绘制选择35个中药成分作为模型药物，考察不同微乳液相体系对其药动学参数的预测能力，筛选预测药动学参数的最优体系。利用最优微乳体系和支持向量机（SVM）回归建立QRAR。以丹参中主要的水溶性和脂溶性成分作为测试集，对回归模型的预测能力进行验证。结果显示模型具有良好的预测能力和稳健性。最后，利用该QRAR模型绘制出丹参药动学指纹图谱。
[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.
【学位授予单位】：广东药学院
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R96

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