Process Study On Acarbose Separation From Actinoplanes Utahensis ZJB-08196 Broth

Acarbose is an oral alpha-glycosidase inhibitor used in the management of non-insulin-dependent diabetes mellitus(NIDDM).Reling on its high security,favorable pharmacology kinetic and low toxicity,acarbose could be used on dropping blood sugar,lighten on blood sugar undulating,guarding against angiocardiopathy as well as adjusting lipid metabolizing in vivo.Acarbose becomes to be an ideal drug so far as it's being on the market.However,the fermentation and separation study of acarbose are still insufficiency.The main point of this research had analyzed the isotherm,kinetic,thermodynamics and fixed-bed performance of acarbose adsorption onto cation exchange resins.And a process of extraction and purification of acarbose from Actinoplanes utahensis ZJB-08196 fermentation broth was also studied in this thesis.Static experiments showed that acarbose get maximum adsorption capacity on five resins at nature pH.Its adsorption capacity decrease when the pH value of the system is lower than pKa1 or higher than pKa2.The temperature equilibrium experiments indicated that the order of the capacity of the five resins is 001×4>HZ016>001×7>HZ001>PT151 and their capacities were heightened by increasing temperature but the capacity added value of PT151 was mostly low.Thermodynamics of the adsorption could be obtained by predicting ln(qe/Ce)versus qe and Van't Hoff plot.The results showed that ?G is negative whereas those of AS and ?H are positive,demonstrating that acarbose adsorption onto cation exchange resins are endothermic,therefore elevating temperatures is advantageous to this process.Langmuir isotherm is the best model for the equilibrium adsorption.Stir batch experiment data was predicted by Pseudo-first-order model,Pseudo-second-order model and intra-particle diffusion model.The results illustrated that the speed of acarbose exchanging onto sites of resin is not to be the control step.That means the adsorption of chemical process is not the control step of the kinetic of the adsorption.Three speed parameters of the adsorption,which were predicted by the intra-particle diffusion model,was minished with time.This explained the speed of adsorption at the beginning of the adsorption is pretty quick but becoming slow as the resistance of adsorption filling out with time.Fixed-bed experiments had investigated that influent acarbose concentration and flow rate and the ratio of bed height to its diameter affected the adsorption on fixed bed.The dynamic adsorption capacity was raised by some degree as the rising influent acarbose concentration.The breakthrough curve become steep and the bed become more efficient with the heightening bed or the reducing flow rate.By the study of the five beds,HZ001 and HZ016 beds possess short mass transfer zone and steeper breakthrough curve than the others.The fermentation broths were pretreated with ethanol precipitation and desalt process.The results were protein removal ratio of 89.45%,sugar removal ratio of 88.14%,desalt ratio of 95.77%and purity of 23.64%after pretreatment.The adsorption capacities of acarbose from fermentation broth by the five resins were increased several times with pretreatment.The removal of impurities enormously decreased the obstruction of adsorption.The preliminary extraction experiments showed HZ001 bed displays best.Its bed adsorption capacity of 623.0 mg/g,the ratio of bed capacity to its maximum capacity of 81.29%,protein removal ratio of 98.52%,sugar removal ratio of 86.36%,color materials removal ratio of 95.36%,impurities removal ratio of 87.93%and yield of 97.86%were obtained.The further extraction experiments showed PT151 bed performances best.Bed adsorption of 348.2 mg/g,the ratio of bed capacity to its maximum capacity of 88.78%,impurities removal ratio of 87.42%and yield of 91.30%were obtained.Pretreatment,preliminary extraction,anion exchange neutralization,further extraction and being dried have investigated in the process.The final results were yield of 87.88%and purity of 87.36%.This study has explored a convenient method of extraction acarbose from fermentation broth.The process is favorable and of highly yield by using two cation exchange resins in this method,which is compared with traditional process in separation of acarbose.