Surface Molecular Imprinting And Hollow Fiber Membrane For High-performance Separation Of Chiral Drug Amlodipine

Scientists and medical workers through a large number of scientific research and clinical trials have demonstrated that the different chiral drug molecules enantiomers have different curative effect,and some of them have toxic side effects even.Cardiovascular disease,which has characteristics with high morbidity and high mortality,is a serious threat to the safety of human life for increased incidence year by year.The dosage of chiral drug amlodipine besylate for the treatment of cardiovascular diseases was growing.The curative effect of?S?-amlodipine besylate??S?-ADB?is 2,000 times higher than?R?-amlodipine besylate??R?-ADB?.Therefore,it is very meaningful and imperative to obtain pure chiral amlodipine besylate.The development of new drugs can't meet the demand for drugs at this stage because of the limitation of various factors,such as long cycle and high cost.Therefore,it is of great significance to develop an efficient and low-cost method for the separation of enantiomers of industrial production.In this paper,cardiovascular chiral drug amlodipine besylate as the research object,molecular imprinting technique and hollow fiber membrane were used through dynamic adsorption and the cross-flow of homemade membrane components to the separation of amlodipine besylate and have a good the percentage of enantionmeric excesses?% e.e.?,1.The hollow fiber membrane?PVDF?was served as the base material to compound the surface molecularly imprinted polymers of maleic acid?MA?and N,N-methylene bis acrylamide?MBA?for chiral separation of amlodipine besylate.The infrared spectra and scanning electron microscopy showed that the PVDF@MIP composite film was successfully prepared.The factors which could influence the separation of enantiomers,such as the dosage of MA,the dosage of MBA and the dosage of template,were investigated and the optimum molar ratio was 1:4:0.125.The target concentration,pH value and flow velocity of the cross flow system were also investigated.The results show that the adsorption capacity is 4.57 ?mol L^-1,the percent of enantiomers excess is about 59.07%,and the corresponding separation factor is about 3.89.2.The chiral separation of amlodipine besylate was carried out by using the polymer system of ?-CD and MA through the use of the PVDF hollow fiber membrane as the base material.The types of ?-CD,which can affect the resolution of pH,were investigated,including Me-?-CD,HP-?-CD and SBE-?-CD,the amount of ?-CD,the concentration of target,the value of flow,the flow velocity all of them were investigated too.The best percent of enantiomers excess is 36.5%,and the corresponding separation factor is 2.15.3.Silica microspheres as supporter to surface molecularly imprinted polymers,?S?-amlodipine besylate molecularly imprinted polymer were psrepared with high capacity,the synthesis conditions were optimized and explored through adsorption properties.The materials were characterized by IR,TGA and SEM.The results showed that the molecularly imprinted polymer was successful polymerization on the surface of silicon spheres.The best ratio of monomer: template: crosslinking agent is 1:3:0.25?molar ratio?,the optimized synthesis of molecularly imprinted polymer material filled in glass column,completed the dynamic column separation of amlodipine.The theoretical adsorption capacity obtained by molecular imprinting is 87.72 mg g^-1.