多级离心萃取分离酮康唑和2-苯基丙酸对映体的研究

发布时间：2018-07-02 11:35

  本文选题：手性分离 + 离心萃取技术　； 参考：《湖南大学》2016年硕士论文

【摘要】：手性制药是医药行业的前沿领域,手性拆分法是获得单一对映体药物的最常用方法。随着人们对于单一对映体药物的需求日益增长,各种手性分离技术得到了迅速发展。本论文以亲水性β-环糊精衍生物为手性萃取剂,运用离心萃取技术,对酮康唑和2-苯基丙酸对映体进行了多级离心萃取分离研究。基于单级萃取理论模型、质量守恒定律并结合相平衡方程,分别建立了多级离心萃取分离酮康唑对映体和2-苯基丙酸对映体的数学模型,并运用Matlab软件平台编写模拟程序。利用建立的模型对多级离心萃取分离过程进了模拟和优化,获得了一系列多级离心萃取分离过程的规律和较佳工艺操作参数,这些都为酮康唑和2-苯基丙酸对映体的分离以及离心萃取器的设计和放大提供了科学依据。本论文的主要研究工作和结果如下：1、多级离心萃取分离酮康唑对映体的研究：在温度为5℃,以乙酸丁酯为有机溶剂,水相中萃取剂羟丙基-p-环糊精(HP-β-CD)浓度为0.1 mol/L时,通过单相识别手性萃取实验得到了分离酮康唑对映体的分离因子为1.32。基于酮康唑对映体的单级萃取理论模型和质量守恒定律并结合相平衡方程,建立了多级离心萃取手性分离酮康唑对映体数学模型,并运用Matlab平台编写模拟程序。通过实验和模拟考察了体积流量比(W/O和W/F)、萃取剂HP-β-CD浓度、水相pH值、以及萃取级数等工艺参数对多级离心萃取分离酮康唑对映体萃取性能的影响。通过模拟预测和优化获得了多级离心萃取对称分离酮康唑对映体的重要结论：在温度为5℃下,当体积流量比W/O为3.3,体积流量比W/F为40,萃取剂HP-β-CD浓度为0.1 mol/L,水相pH为8.5的条件下,当萃取级数为72级时,eeeq能达到97%以上,当萃取级数为94级时,eeeq能达到99%以上2、多级离心萃取分离2-苯基丙酸对映体的研究：基于2-苯基丙酸对映体的单级萃取理论模型和质量守恒定律并结合相平衡方程,建立了多级离心萃取于性分离2-苯基丙酸对映体数学模型,并运用Matlab平台编写模拟程序。通过实验和模拟考察了体积流量比(W/O和W/F)、萃取剂HP-β-CD浓度、水相pH值及萃取级数等工艺参数对多级离心萃取分离2-苯基丙酸对映体萃取性能的影响。通过模拟预测和优化获得了多级离心萃取对称分离2-苯基丙酸对映体的重要结论：在温度为5℃下,体积流量比W/O为0.55,体积流量比W/F为40,萃取剂HP-β-CD浓度为0.1 mol/L,水相pH为2.5的条件下,当萃取级数为98级时,eeeq能达到95%以上,当萃取级数为106级,eeeq能达到97%以上。
[Abstract]:Chiral pharmaceuticals are the frontiers of the pharmaceutical industry. Chiral separation is the most commonly used method for obtaining mono enantiomers. With the increasing demand for single enantiomers, chiral separation techniques have developed rapidly. This paper uses hydrophilic beta cyclodextrin derivatives as chiral extractors and centrifuge extraction technology. Multistage centrifugal extraction was carried out for the enantiomers of ketoconazole and 2- phenyl propionic acid. Based on the theoretical model of the single stage extraction, the law of mass conservation and the phase equilibrium equation, the mathematical model of the separation of ketoconazole enantiomers and 2- phenyl propionic acid enantiomers was established by multistage centrifugal extraction, and the simulation program was written with the Matlab software platform. The separation process of multistage centrifugal extraction was simulated and optimized by the established model. A series of multistage centrifugal extraction separation process and the better process parameters were obtained. These all provided scientific basis for the separation of the enantiomers of ketoconazole and 2- phenyl propionic acid and the design and enlargement of the centrifugal extractor. The results are as follows: 1, study on the enantiomers of ketoconazole by multistage centrifugal extraction: at the temperature of 5, butyl acetate was used as organic solvent and the concentration of hydroxypropyl -p- cyclodextrin (HP- beta -CD) in aqueous phase was 0.1 mol/L, the separation factor of the separation of ketoconazole enantiomers was 1.32. based on the single phase recognition chiral extraction experiment. A mathematical model of chiral separation of ketoconazole enantiomers by multistage centrifugal extraction was established on the single stage extraction theory model of ketoconazole and the law of mass conservation and the phase equilibrium equation. The simulation program was compiled with Matlab platform. The volume flow ratio (W/O and W/F), the concentration of HP- beta -CD and the pH value of the aqueous phase were investigated by experiment and simulation. The effect of the extraction series and other technological parameters on the separation of ketoconazole enantiomers by multistage centrifugal extraction. The important conclusion of the separation of ketoconazole by multistage centrifugal extraction was obtained by simulated prediction and optimization. At the temperature of 5, the volume flow ratio W/O was 3.3, the volume flow rate was 40 and the concentration of HP- beta -CD of the extractant. Under the condition of 0.1 mol/L and 8.5 water phase, when the extraction series is 72, the eeeq can reach more than 97%. When the extraction series is 94, eeeq can reach 2. Multistage centrifugal extraction is used to separate the enantiomers of 2- phenyl propionic acid: Based on the single stage extraction theory model and the mass conservation law of 2- phenyl propionic acid and the law of mass conservation and phase equilibrium A multistage centrifuge extraction was established for the enantiomeric model of 2- phenyl propionic acid, and the simulation program was written on the Matlab platform. The volume flow ratio (W/O and W/F), the concentration of HP- beta -CD, the pH value of the aqueous phase and the extraction series of the aqueous phase were investigated by experiment and simulation. The enantiomer extraction of 2- phenyl propionic acid was extracted by multistage centrifugal extraction. An important conclusion for the enantiomers of 2- phenyl propionic acid by multistage centrifugal extraction is obtained by simulated prediction and optimization. At 5 C, the volume flow ratio is 0.55, the volume flow rate is 40, the concentration of HP- beta -CD is 0.1 mol/L, and the pH of the water phase is 2.5, and the eeeq can reach 95% when the extraction series is 98. Above, when the extraction stage is 106, eeeq can reach more than 97%.
【学位授予单位】：湖南大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：O658.2
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本文编号：2089989