节点文献
手性萃取药物对映体动力学研究
Study on Kinetics of Enantioselective Extraction of Drug Enantiomers
【作者】 蔡剑；
【作者基本信息】 湘潭大学 ， 化学工程与技术， 2012， 硕士
【摘要】 本论文研究了用水溶性β-环糊精从有机相萃取疏水性药物对映体到水相的动力学过程。建立了手性萃取药物对映体的动力学模型，获得了手性萃取药物对映体的最佳萃取条件。其主要实验内容和结果如下：在布洛芬萃取体系中，用伴随着化学反应的萃取理论描述了羟丙基--环糊精萃取布洛芬对映体的内在动力学过程。实验分别研究了搅拌速度，界面面积，布洛芬对映体初始浓度、萃取剂初始浓度，水相的pH值对萃取初始速率影响。实验结果表明：萃取反应对布洛芬对映体浓度为一级反应，对羟丙基--环糊精浓度为二级反应；R-和S-对映体反应速率常数分别为4.58×10-4m6/（mol2·s）和7.21×10-4m6/（mol2·s）。通过动力学模型预测值与实验值的比较发现，动力学模型预测值与实验值完全吻合。在普拉洛芬萃取体系中，用伴随着化学反应的萃取理论描述了甲基--环糊精萃取普拉洛芬对映体的内在动力学过程；通过恒界面池法对甲基--环糊精萃取普拉洛芬对映体的动力学研究表明其动力学过程位于分区理论的第三区即快速的化学反应；实验分别研究了搅拌速度，界面面积，普拉洛芬对映体初始浓度、萃取剂初始浓度，水相的pH值对萃取初始速率影响。实验结果表明：萃取反应对普拉洛芬对映体浓度为一级反应，对甲基-β-环糊精浓度为二级反应；R-和S-对映体反应速率常数k1,2,S和k1,2,S分别为3.53×10-4mol-2·s-1和2.82×10-4mol-2·s-1；通过动力学模型预测值与实验值的比较发现，动力学模型预测值与实验值完全吻合。在奥昔布林萃取体系中，通过恒界面池研究了以羟丙基--环糊精作为萃取剂从有机相中萃取奥昔布林对映体到水相的动力学过程。实验分别研究了搅拌速度，界面面积，奥昔布林对映体初始浓度、萃取剂初始浓度，水相的pH值对萃取初始速率影响。实验结果表明：萃取反应对奥昔布林对映体浓度为一级反应，对羟丙基--环糊精浓度为二级反应；R-和S-对映体反应速率常数k1,2,R和k1,2,S分别为6.12×10-5m6·mol-2·s-1和1.13×10-4m6·mol-2·s-1；通过动力学模型预测值与实验值的比较，发现动力学模型预测值与实验值完全吻合。
【Abstract】 This paper reports on kinetics of reactive extraction of hydrophobic drugenantiomers from the organic phase to the aqueous phase by hydrophilic-CDsolution. The model of kinetics of reactive extraction was established and obtain theoptimal extraction conditions. The main contents and results can be summarized asfollows:In ibuprofen （IBU） extraction system, the theory of extraction accompanied bychemical reactions has been used to obtain the intrinsic kinetics of extraction of IBUenantiomers by hydroxypropyl-β-cyclodextrin （HP--CD）. The effects of processparameters including agitation speed, interfacial area, initial concentration IBUenantiomers, initial concentration of extractant and pH value of aqueous phase, oninitial extraction rate were separately studied. The reactions are first order in IBU andsecond order in HP--CD with the forward rate constants of7.21×10-4mol-2m6s-1for S-IBU and4.58×10-4mol-2m6s-1for R-IBU, respectively. By comparison of theexperimental values with the model predictions, it is found that the model predictionsare in good agreement with the experiment.In pranoprofen （PRA） extraction system, the theory of extraction accompaniedby a chemical reaction has been used to obtain the kinetics. The reactions betweenmethyl-β-cyclodextrin （Me--CD） and PRA enantiomers in a stirred cell fall inRegime3, extraction accompanied by a fast chemical reaction in the diffusion film.The effects of process parameters including agitation speed, interfacial area, initialconcentration of PRA enantiomers, initial concentration of extractant and pH value ofaqueous phase, on initial extraction rate were separately studied.The reactions are firstorder with respect to PRA and second order with respect to Me--CD. The forwardrate constants are2.82×10-4m6/（mol2s） for S-PRA and3.53×10-4m6/（mol2s） forR-PRA, respectively. By comparison of the experimental values with the modelpredictions, it is found that the model predictions are in good agreement with theexperiment.In oxybutynin （OBN） extraction system, the kinetic experiments were carried out ina modified Lewis cell, in which hydrophobic OBN enantiomers was initiallydissolved in the organic solvent and extracted into the aqueous phase byhydroxypropyl-β-cyclodextrin （HP--CD）. The effects of process parameters including agitation speed, interfacial area, initial concentration of OBN enantiomers,initial concentration of extractant and pH value of aqueous phase, on initial extractionrate were separately studied. Results show that the extraction reaction kinetics is fast.The reactions are first order with respect to OBN and second order with respect toHP--CD. The forward rate constants are6.12×10-5m6·mol-2·s-1for R-OBN and1.13×10-4m6·mol-2·s-1for S-OBN, respectively. By comparison of the experimentalvalues with the model predictions, it is found that the model predictions are in goodagreement with the experiment.