Ion Exchange Resin Separation Miglitol Application Of Basic Research

Chemical method and chemical-biological method are mainly used to synthesize miglitol as an important diabetes drug, The chemical-biological method synthesis route of miglitol is paid more attention due to superiority of the short of synthesis route.mild conditions and the higher yield. Meanwhile, high purity of the product is application prerequisite as raw drug. Therefore, it is an important key issue to study separation process of miglitol for characteristics of chemical-biological method. In view of the special chemical structure of miglitol and related substance, the basic data in the separation and purification is relative lack. In this paper, the basic rules and the technology conditions of the adsorption purification process are investigated with the interaction of miglitol and ion exchange resin as object.The main research contents and conclusions are as follows:1. The test conditions of wavelength, absorbency and concentration in spectrophotometer were investigated to establish simpler test method for the monitoring technology process of miglitol and N-hydroxyethyl glucosamine concentration.The test method is proved feasible by the method of the accuracy and precision analysis.2. In the adsorption equilibrium experiment, the types of adsorption medium, initial concentrations of miglitol, temperatures, pH values were discussed to study adsorption equilibrium effects for miglitol adsorbed onto resin. Furthermore, adsorption thermodynamics, equilibrium adsorption models, scanning electron microscope and pore structure analysis were investigated to analysize adorption behaviors of miglitol and resins.The results showed that there is high adsorption capacity of D001resin as separation medium.The adsorption equilibrium at different initial concentrations of miglitol is followed by Langmuir model. The higher is the temperature, the more is unfavourable to miglitol adsorbed onto the resin D001.and the ion exchange process is exothermic chemical process.The values of surface coverage fraction of resin(θ) gradually decline with increasing temperature.The values of θ gradually increase with increasing miglitol concentration.There is high adsorption capacity of resin for miglitol in neutral condition and the surface of absorbed resin increases, and meanwhile, the values of the pore area,pore volumn and pore diameter fall.3. The external effect factors of resin adsorption capacity including initial concentration of miglitol, temperature and stirring rates were investigated respectively to study ion exchange process of miglitol onto resin. The results showed that the adsorption time for miglitol onto D001resins continues3hours and can reach adsorption equilibrium.The greater is the initial concentration, the faster is absorption rate and equilibrium adsorption capacity of resin is also bigger. The higher are the temperature and stirring rate, ion exchange equilibrium time is shorter and the adsorption rate is faster correspondingly. Nevertheless, there is a critical value for stirring rate on effect of ion exchange adsorption process.In addition, the ion exchange process is in accord with typel pseudo-second order kinetic model and is mainly controlled by film diffusion.The value changes of concentration, temperature and stirring rate are affected weakly to control mass transfer diffusion process during the ion exhange process. The related substance N-hydroxyethyl glucosamine is more easy to be adsorbed onto resins D001in contrast to that of miglitol, the adsorption equilibrium at different initial concentrations of N-hydroxyethyl glucosamine is also followed by Langmuir mathmetics model. Meanwhile, their ion exchange kinetic models are similar.4. The factors of concentration, flow rate, temperature, height to diameter ratio (H/D), fixed bed stacking height and the types of eluents, concentration and flow rate of eluent were separately discussed to study adsorption and elution law of miglitol in the fixed bed.The results showed that the saturation point of time is shortened with increasing influent concentration, height of mass transfer zone (MTZ) increases and the value of adsorption ratio (A) decreases. The influent concentration8mg/mL and flow rate0.7mL/min for adsorption capacity is the maximum. The kinetic model fitting analysis for the ion exchange process in the fixed bed shows that Thomas model and Yoon-Nelson model has better fitting degree.The solution temperature on effect of adsorption process is weak. The value of height to diameter ratio is smaller, the corresponding adsorption efficiency (AE) and value of A is larger. The higher is the stacking height of the fixed bed, the greater is the adsorption capacity of resin. The ion exchange process is fitted by bed depth service time (BDST) model and reachs good fit degree, the calculated value of the volume adsorption capacity (No) and rate constant of BDST model (Ka) differ little. The ammonia water is selected as eluent, the greater is concentration of ammonia water and the flow rate is lower, the elution quantity is also biger. In addition, the stacking height of the fixed bed is1.5cm and the value of elution efficiency reaches the largest.5. The ion exchange separation process in the fixed bed for the different mass ratios of miglitol to N-hydroxyethyl glucosamine was discussed by influent concentrations, flow rate, height to diameter ratio, stacking height, concentration and flow rate of eluent, respectively. The results showed that the values of adsorption efficiency gradually increases and the values of adsorption ratio declines with increasing miglitol concentration. There is a small value of mass transfer zone with the greater flow rate, the corresponding values of adsorption efficiency and adsorption ratio obviously augments. The greater is the value of height to diameter ratio and corresponds with the small value of D001resin adsorption capacity, the values of adsorption efficiency and adsorption ratio are all smaller. The bigger is the stacking heigh in fixed bed. the adsorption capacity, the values of adsorption efficiency and adsorption ratio are all increasing. The adsorbed ions were eluted for the fixed mass ratio mixture. The results showed that there are a higher mass ratio of miglitol to N-hydroxyethyl glucosamine in effluent solution mixture with a greater concentration and a lower flow ratio of ammonia water.The different mass ratios mixture were eluted and investigated by ammonia water, it was found that the adsorbed samples are eluted more obvious with the higher miglitol mass ratio in the influent mixture.The mass ratio of miglitol to N-hydroxyethyl glucosamine in the effluent solution mixture reaches62.6:1when the influent mass ratio of miglitol to N-hydroxyethyl glucosamine is9:1,the purity of miglitol is from90.0%to over98.0%. In addition, the adsorbed samples in different fixed bed stacking heights were also eluted and found that the elution results is better when the stacking height is1.5cm in the fixed bed, the mass ratio of miglitol to N-hydroxyethyl glucosamine in effluent solution mixture is the best. The elution curves of miglitol and N-hydroxyethyl glucosamine are obviously optimized by prolonging the stacking height in the fixed bed, establishs elution kinetic model and summarizes the separation law of the matters.