本文選題：手性分離 + 離心萃取技術(shù)��； 參考：《湖南大學(xué)》2016年碩士論文

【摘要】：手性制藥是醫(yī)藥行業(yè)的前沿領(lǐng)域,手性拆分法是獲得單一對映體藥物的最常用方法。隨著人們對于單一對映體藥物的需求日益增長,各種手性分離技術(shù)得到了迅速發(fā)展。本論文以親水性β-環(huán)糊精衍生物為手性萃取劑,運用離心萃取技術(shù),對酮康唑和2-苯基丙酸對映體進行了多級離心萃取分離研究�；趩渭壿腿±碚撃Ｐ汀①|(zhì)量守恒定律并結(jié)合相平衡方程,分別建立了多級離心萃取分離酮康唑?qū)τ丑w和2-苯基丙酸對映體的數(shù)學(xué)模型,并運用Matlab軟件平臺編寫模擬程序。利用建立的模型對多級離心萃取分離過程進了模擬和優(yōu)化,獲得了一系列多級離心萃取分離過程的規(guī)律和較佳工藝操作參數(shù),這些都為酮康唑和2-苯基丙酸對映體的分離以及離心萃取器的設(shè)計和放大提供了科學(xué)依據(jù)。本論文的主要研究工作和結(jié)果如下：1、多級離心萃取分離酮康唑?qū)τ丑w的研究：在溫度為5℃,以乙酸丁酯為有機溶劑,水相中萃取劑羥丙基-p-環(huán)糊精(HP-β-CD)濃度為0.1 mol/L時,通過單相識別手性萃取實驗得到了分離酮康唑?qū)τ丑w的分離因子為1.32�；谕颠�?qū)τ丑w的單級萃取理論模型和質(zhì)量守恒定律并結(jié)合相平衡方程,建立了多級離心萃取手性分離酮康唑?qū)τ丑w數(shù)學(xué)模型,并運用Matlab平臺編寫模擬程序。通過實驗和模擬考察了體積流量比(W/O和W/F)、萃取劑HP-β-CD濃度、水相pH值、以及萃取級數(shù)等工藝參數(shù)對多級離心萃取分離酮康唑?qū)τ丑w萃取性能的影響。通過模擬預(yù)測和優(yōu)化獲得了多級離心萃取對稱分離酮康唑?qū)τ丑w的重要結(jié)論：在溫度為5℃下,當(dāng)體積流量比W/O為3.3,體積流量比W/F為40,萃取劑HP-β-CD濃度為0.1 mol/L,水相pH為8.5的條件下,當(dāng)萃取級數(shù)為72級時,eeeq能達到97%以上,當(dāng)萃取級數(shù)為94級時,eeeq能達到99%以上2、多級離心萃取分離2-苯基丙酸對映體的研究：基于2-苯基丙酸對映體的單級萃取理論模型和質(zhì)量守恒定律并結(jié)合相平衡方程,建立了多級離心萃取于性分離2-苯基丙酸對映體數(shù)學(xué)模型,并運用Matlab平臺編寫模擬程序。通過實驗和模擬考察了體積流量比(W/O和W/F)、萃取劑HP-β-CD濃度、水相pH值及萃取級數(shù)等工藝參數(shù)對多級離心萃取分離2-苯基丙酸對映體萃取性能的影響。通過模擬預(yù)測和優(yōu)化獲得了多級離心萃取對稱分離2-苯基丙酸對映體的重要結(jié)論：在溫度為5℃下,體積流量比W/O為0.55,體積流量比W/F為40,萃取劑HP-β-CD濃度為0.1 mol/L,水相pH為2.5的條件下,當(dāng)萃取級數(shù)為98級時,eeeq能達到95%以上,當(dāng)萃取級數(shù)為106級,eeeq能達到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%.
【學(xué)位授予單位】：湖南大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2016
【分類號】：O658.2
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本文編號：2089989