【作者】 郑文坚；

【导师】 朱家文；

【作者基本信息】 华东理工大学 ， 化学工程， 2012， 硕士

【摘要】 红霉素是一种重要的大环内酯类抗生素,工业上由微生物发酵而得,其下游分离纯化工艺一直是红霉素生产的关键。现有的红霉素分离工艺还难以高收率的提取主产物红霉素A的同时,去除主要副产物红霉素C。为此,本文开发一条新的红霉素提取和纯化工艺,它采用大孔树脂HZ816固定床动态吸附经50nm陶瓷膜过滤的发酵液中的红霉素,经碱性缓冲盐溶液洗涤树脂后用乙酸丁酯解吸红霉素,然后往此红霉素丁酯解吸液中加入不混溶的磷酸盐缓冲液,利用乙酸丁酯和水产生的非均相共沸移走乙酸丁酯,红霉素则转移到磷酸盐缓冲液中,最后往磷酸盐缓冲液中加入碱调高pH,使得红霉素在水相中结晶出来。研究表明：(1)树脂固定床吸附红霉素符合Adams-Bohart吸附模型,吸附穿透损失是吸附量、进料流速和进料液红霉素浓度三者的函数；当吸附量控制在树脂饱和吸附量(123mg/ml)的60%左右时,对不同浓度的进料液采用合适的进料流速(两者大小相反),可使吸附收率达98%。(2)用碱性缓冲盐溶液洗涤树脂后可以将树脂上离子态的红霉素转为游离碱态,从而大大提高后续乙酸丁酯解吸红霉素的速率和收率,减少乙酸丁酯用量；较为合适的碱性缓冲盐溶液是pH9.4的氯化铵-氨水；后续解吸用乙酸丁酯以0.5倍床层体积每小时的流速洗脱,收集1.2倍固定床体积的红霉素酯相溶液即可使解吸收率达98%,得到浓度为61.5mg/ml左右的红霉素乙酸丁酯溶液。(3)共沸蒸馏可以移除乙酸丁酯,使得红霉素从乙酸丁酯相转移到K2HPO4-KH2PO4缓冲水溶液中,相转移收率可达96%；之后在50℃～55℃下逐渐加入4%的稀氨水至pH到9.6～9.8时,红霉素A的结晶收率可达96%,而红霉素C的收率仅为50%左右。通过上述研究实现了红霉素从在树脂上吸附、解吸再到水相结晶的整条分离纯化工艺,该工艺对红霉素A的总收率可达89%,对红霉素C为46%左右,可从发酵滤液中得到高质量的红霉素产品。更多还原

【Abstract】 Erythromycin is an important kind of macrolide antibiotics, which is obtained from microbial fermentation in industry. The downstream separation and purification process is the key to production of erythromycin. Existing erythromycin separation processes are yet unable to recover principal product, erythromycin A, with high yield and remove the main byproduct, erythromycin C, at the same time. For this reason, this article developed a new erythromycin recovery process, which employs macroporous resin HZ816fixed-bed to adsorb erythromycin from fermentation liquid filtrated by50nm ceramic membrane, uses butyl acetate to desorb erythromycin from resin after washing resin with alkali buffer solution, then transfers erythromycin to phosphate buffer solution by carrying out heterogeneous azeotropic distillation of butyl acetate and water after adding immiscible phosphate buffer solution to erythromycin butyl acetate solution, and then crystalizes erythromycin by adding alkali to this phosphate buffer solution to increase pH.It turned out that:(1) Adams-Bohart adsorption model could fit erythromycin adsorption onto resin fixed-bed. Adsorption breakthrough loss was the function of adsorption amount, feeding flow velocity and feeding erythromycin concentration. When the adsorption amount was60%of the saturated amount, the adsorption yield could be98%at appropriate feeding flow velocity for different feeding erythromycin concentrations.(2) Protonized erythromycin could be converted to erythromycin alkali by washing resin with alkali buffer solution, thus the erythromycin desorption rate and yield increased and the consumption of desorbing agent, butyl acetate, decreased. Ammonia-ammonium chloride solution was a suitable choice for this process. After washing, desorption was carried out by butyl acetate at feeding flow rate of0.5fixed-bed volume per hour, and the yield of desorbed erythromycin in the first1.2fix-bed volume butyl acetate elution could be98%. The erythromycin concentration in butyl acetate elution was about61.5mg/ml.(3) Erythromycin could be transferred into aqueous solution after azeotropic distillation of butyl acetate and water and the yield could be96%. Then,4%ammonia water was added into the erythromycin aqueous solution until pH was9.6-9.8at temperature of50-55℃. The crystallization yield of erythromycin A could be96%while that of erythromycin C was only about50%.A whole erythromycin separation and purification process which consists of erythromycin adsorption, desorption and aqueous crystallization was established. It can recover erythromycin with yield of erythromycin A of89%and erythromycin C of46%, therefore can obtain high quality erythromycin from fermentation filtrate.更多还原