【作者】 刘敏；

【导师】 何潮洪；

【作者基本信息】 浙江大学 ， 化学工程与技术， 2020， 硕士

【摘要】 氨氯地平是一种强效的第三代二氢吡啶钙通道拮抗剂,被世界卫生组织临床抗高血压治疗推荐为一线抗高血压药物,具有作用温和、降压平稳、长效安全等优点。然而,在大鼠主动脉的体外评估实验中,S-氨氯地平的药效是R-氨氯地平的2000倍。在使用过程中两种对映体及其盐表现出不同的药理特性,且R-氨氯地平使得周围血管释放一氧化氮,从而导致周围血肿。因此为用药安全有效,获得单一 S-氨氯地平对映体具有重要意义。手性离子液体是一种具有独特手性识别能力的手性选择剂,在萃取分离方面研究较多,但是其粘度高、传热传质不易、成本高难回收以及不易降解等问题限制了其在工业上的应用。为了克服手性离子液体在萃取过程中的缺陷,本文将手性氨基酸离子液体负载在固体基质上,以固定化离子液体为拆分剂,对氨氯地平对映体的拆分过程进行了研究。主要研究内容有:1.为了实现手性氨基酸离子液体的循环回用,本文采用化学键合法制备了一种新型的咪唑基L-谷氨酸固定化手性离子液体,并考察了基质种类、反应溶剂以及碱化时间等因素对于制备过程的影响,通过红外光谱、固体核磁、热重分析、X-射线衍射等手段对实验产物进行了表征。2.将合成的固定化咪唑基L-谷氨酸离子液体用于吸附溶液中S-氨氯地平,研究了吸附剂对S-氨氯地平的吸附性能。探讨了吸附过程中吸附时间、S-氨氯地平初始浓度、溶液pH值以及吸附温度对吸附量的影响,并对实验数据进行了吸附动力学模型与等温吸附模型拟合。3.为考察固定化离子液体对氨氯地平对映体的拆分效果,将合成的固定化离子液体填充成固相萃取柱,研究了样品浓度、样品体积、洗脱液组成、洗脱流速等因素对固相萃取柱分离特性的影响。4.采用液-液-固萃取方法,以固定化咪唑基L-谷氨酸离子液体为固相手性选择剂、氨氯地平水溶液为水相、有机溶剂为油相,液-液-固手性拆分氨氯地平对映体。考察了油相种类、萃取剂用量、料液初始浓度、萃取温度等对液-液-固手性拆分氨氯地平效果的影响。更多还原

【Abstract】 Amlodipine is a powerful third-generation dihydropyridine calcium channel antagonist,which has the advantage of moderate reaction,stable hypotension and long-term safety and is recommended as the first-line antihypertensive drug by the World Health Organization for clinical antihypertensive treatment.However,when amlodipine racemic compounds were used in treatment in vitro in rat aortic evaluation,S-amlodipine is 1000 times more potent than R-amlodipine,while R-amlodipine may cause the release of nitric oxide in peripheral blood vessels and lead to peripheral hematoma.Two enantiomers and their salts have different pharmacological properties.Therefore,it is important to obtain a single S-amlodipine enantiomer in order to use it safely and effectively.Chiral ionic liquid(CIL)is a chiral selective agent with unique chiral recognition ability.There are many researches about CIL on extraction and separation,while its application in industry is limited by its high viscosity,difficult heat and mass transfer,high cost,difficult recovery and degradation.In order to overcome the defects of chiral ionic liquid in the extraction process,the separation of amlodipine enantiomers was studied by immobilized chiral ionic liquid on the substrate.The main contents are summarized as follows:1.A novel L-glutamate based immobilized chiral ionic liquid was prepared by chemical bonding method to recycle the chiral amino ionic liquid.The influence of substrate type,reaction solvent and alkalization time on the load amount of ionic liquid was studied,and the product was characterized by infrared spectroscopy,solid nuclear magnetism,thermogravimetric analysis,X-ray diffraction,etc.2.The performance of prepared immobilized ionic liquid was investigated for the absorption of S-amlodipine.The effects of adsorption time,initial concentration of S-amlodipine,pH value of solution and temperature on adsorption amount were investigated,and the experimental data was correlated by kinetic adsorption model and isotherm adsorption model.3.In order to investigate the separation effect of immobilized ionic liquid on amlodipine enantiomers,the immobilized ionic liquid was used to fill the glass chromatographic column.The influences of conditions such as sample concentration,sample volume,eluent composition,elution velocity,etc on the separation characteristic of solid phase extraction(SPE)was investigated.4.Amlodipine enantiomers were separated by liquid-liquid-solid extraction.The immobilized imidazolidyl 1-glutamic acid ionic liquid was used as the solid phase chiral selector,the amlodipine aqueous solution was the water phase,and organic solvent was the oil phase.The influence of oil phase types,dosage of extractant,amlodipine concentration and extraction temperature on the resolution of amlodipine were investigated.更多还原