贯流硅胶在生物色谱中的应用

发布时间：2018-05-11 01:10

本文选题：贯流硅胶 + 生物分配胶束色谱　；参考：《华中科技大学》2013年硕士论文

【摘要】：贯流硅胶作为一种新近发展起来的色谱固定相表现出良好的色谱性能。它同时具有中孔和大孔结构,前者有利于增大比表面积,后者有利于加快传质提高柱效并降低柱压[1]。在本论文中,我们以贯流硅胶为色谱基质,将其应用于生物分配胶束色谱(Biopartitioning Micellar Chromatography, BMC)、生物膜色谱(Cell Membrane Chromatography, CMC)以及生物膜固相萃取(Cell Membrane Solid Phase Extraction, CM-SPE)三种模式,分别用于模拟研究二苯甲酮类物质的毒性及透皮性、中药中抗癌活性成分的筛选。第一章利用BMC建立的定量保留-活性关系(Quantitative Retention-Activity Relationships, QRARs)来研究二苯甲酮类紫外吸收剂的生物毒性和透皮性。实验考察了流动相中brij35浓度(0.01,0.02,0.03M)以及流动相pH值(pH6.5,7.4)对紫外吸收剂保留行为的影响,并且将它们在六个色谱条件下的保留参数log K与毒性参数log BCF(生物富集因子(Bioconcentration Factor, BCF))和透皮分数(T)进行了多元线性回归并建立QRARs模型。log BCF与log K的二项式模拟结果的相关系数R2在0.9398～0.9753范围内；T与log K的二项式模拟结果的相关系数R2在0.7569～0.8434之间。结果表明基于贯流C18硅胶的BMC能够很好的模拟二苯甲酮类紫外吸收剂的生物毒性及透皮性。第二章采用以贯流C18硅胶为固定相基质的BMC系统,考察了流动相brij35浓度(0.01,0.02,0.03,0.04M)以及pH值(pH6.5,7.4)对十余种化药保留行为的影响,并利用其相关参数建立了口服药代参数模型,对西地那非及其类似物的口服药代参数进行了预测。第三章采用CMC及CM-SPE两种模式对几种中药中潜在的抗癌活性成分进行了筛选。将宫颈癌Hela细胞膜涂覆于贯流硅胶表面,成为细胞膜材料。该材料分别用于色谱柱固定相和SPE填料,利用癌细胞膜上丰富的表皮生长因子受体对莪术、当归、白花蛇草、黄连、山豆根、败酱草几种中药进行抗癌活性成分的筛选。
[Abstract]:As a newly developed chromatographic stationary phase, tubular silica gel shows good chromatographic performance. It has both mesoporous and macroporous structures, the former is advantageous to increase the specific surface area, and the latter is conducive to accelerating mass transfer and increasing the column efficiency and reducing the column pressure [1]. In this paper, we used tubular silica gel as the chromatographic matrix, and applied it to biopartitioning Micellar Chromatographyy, BMC, biofilm chromatography cell Membrane Chromatography, CMC) and biofilm solid phase extraction (SPE) cell Membrane Solid Phase Extraction, CM-SPE (biofilm solid phase extraction). It was used to simulate the toxicity and transdermal properties of benzophenone, and to screen the anticancer active components in traditional Chinese medicine. In chapter 1, quantitative Retention-Activity relationships (QRARs) established by BMC were used to study the biotoxicity and transdermal properties of benzophenone UV absorbers. The effects of the concentration of brij35 in the mobile phase and pH value of the mobile phase on the retention behavior of UV absorbent were investigated. The retention parameter log K under six chromatographic conditions, the toxicity parameter log BCF (bioconcentration factor) and transdermal fraction T were regressed by multivariate linear regression and the binomial simulation results of QRARs model. Log BCF and log K were established. The correlation coefficient R ~ 2 of the binomial simulation results of T and log K in the range of 0.9398-0.9753 is between 0.7569 and 0.8434. The results show that BMC based on tubular C18 silica gel can well simulate the biotoxicity and transdermal properties of benzophenone UV absorbers. In the second chapter, the effects of mobile phase brij35 concentration (0.01g / 0.02) and pH value (pH 6.5 ~ 7.4) on the retention behavior of more than ten chemotherapeutic agents were investigated by using the BMC system with tubular C18 silica gel as the stationary phase matrix, and the oral pharmacokinetic model was established by using the relevant parameters. The oral pharmacokinetic parameters of sildenafil and its analogues were predicted. In chapter 3, CMC and CM-SPE models were used to screen the potential anticancer active components in several traditional Chinese medicines. The Hela membrane of cervical cancer was coated on the surface of tubular silica gel to become membrane material. The material was used for chromatographic column stationary phase and SPE packing respectively. The active components of anticancer were screened by using the abundant epidermal growth factor receptor (EGF) on cancer cell membrane of Rhizoma Curcumae, Angelica sinensis, Ophiophora sinensis, Rhizoma Coptidis, Radix Sophora root and Herba abortus.
【学位授予单位】：华中科技大学
【学位级别】：硕士
【学位授予年份】：2013
【分类号】：R318.08

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