貫流硅膠在生物色譜中的應(yīng)用
發(fā)布時(shí)間:2018-05-11 01:10
本文選題:貫流硅膠 + 生物分配膠束色譜; 參考:《華中科技大學(xué)》2013年碩士論文
【摘要】:貫流硅膠作為一種新近發(fā)展起來的色譜固定相表現(xiàn)出良好的色譜性能。它同時(shí)具有中孔和大孔結(jié)構(gòu),前者有利于增大比表面積,后者有利于加快傳質(zhì)提高柱效并降低柱壓[1]。在本論文中,我們以貫流硅膠為色譜基質(zhì),將其應(yīng)用于生物分配膠束色譜(Biopartitioning Micellar Chromatography, BMC)、生物膜色譜(Cell Membrane Chromatography, CMC)以及生物膜固相萃取(Cell Membrane Solid Phase Extraction, CM-SPE)三種模式,分別用于模擬研究二苯甲酮類物質(zhì)的毒性及透皮性、中藥中抗癌活性成分的篩選。 第一章利用BMC建立的定量保留-活性關(guān)系(Quantitative Retention-Activity Relationships, QRARs)來研究二苯甲酮類紫外吸收劑的生物毒性和透皮性。實(shí)驗(yàn)考察了流動相中brij35濃度(0.01,0.02,0.03M)以及流動相pH值(pH6.5,7.4)對紫外吸收劑保留行為的影響,并且將它們在六個色譜條件下的保留參數(shù)log K與毒性參數(shù)log BCF(生物富集因子(Bioconcentration Factor, BCF))和透皮分?jǐn)?shù)(T)進(jìn)行了多元線性回歸并建立QRARs模型。log BCF與log K的二項(xiàng)式模擬結(jié)果的相關(guān)系數(shù)R2在0.9398~0.9753范圍內(nèi);T與log K的二項(xiàng)式模擬結(jié)果的相關(guān)系數(shù)R2在0.7569~0.8434之間。結(jié)果表明基于貫流C18硅膠的BMC能夠很好的模擬二苯甲酮類紫外吸收劑的生物毒性及透皮性。 第二章采用以貫流C18硅膠為固定相基質(zhì)的BMC系統(tǒng),考察了流動相brij35濃度(0.01,0.02,0.03,0.04M)以及pH值(pH6.5,7.4)對十余種化藥保留行為的影響,并利用其相關(guān)參數(shù)建立了口服藥代參數(shù)模型,對西地那非及其類似物的口服藥代參數(shù)進(jìn)行了預(yù)測。 第三章采用CMC及CM-SPE兩種模式對幾種中藥中潛在的抗癌活性成分進(jìn)行了篩選。將宮頸癌Hela細(xì)胞膜涂覆于貫流硅膠表面,成為細(xì)胞膜材料。該材料分別用于色譜柱固定相和SPE填料,利用癌細(xì)胞膜上豐富的表皮生長因子受體對莪術(shù)、當(dāng)歸、白花蛇草、黃連、山豆根、敗醬草幾種中藥進(jìn)行抗癌活性成分的篩選。
[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.
【學(xué)位授予單位】:華中科技大學(xué)
【學(xué)位級別】:碩士
【學(xué)位授予年份】:2013
【分類號】:R318.08
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