| As a traditional macrolide antibiotic, erythromycin(EM) has become one of the most popular antibiotics due to its features of good curative effect, low side effect and wide clinical use of its derivatives. However, some urgent problems still exist in the present production process of EM, such as the poor quality of products, low extraction efficiency, high consumption of chemicals, and serious pollution of the environment. To solve these problems, an innovative separation process combining the macroporous resin adsorption with the membrane filtration has been proposed in the present paper based on the conception of "green, effective and economic".The main contents and conclusions are as follows:(1) The effect of feed concentration, temperature, bed height and aspect ratio on the fixed-bed adsorption characteristics of EM was investigated by using a macroporous resin SP825 as adsorbent. The general rate model taking the film mass transfer, pore diffusion and axial dispersion into account was adopted to describe the breakthrough curves. The mass transfer coefficients and the relative errors of the model were consequently determined. The results showed that the increase of feed concentration was not in favor of the fixed-bed adsorption performance, while the increase of temperature and aspect ratio could improve the mass transfer. In addition, the variation in bed height had little effect on adsorption characteristics. By calculating the mass Biot number and Peclet number, it is clear that both liquid film mass transfer and pore diffusion play important roles in the fixed-bed adsorption of EM onto SP825, whereas the axial dispersion could be negligible in the experimental range. The relative errors of the model were within 10%, indicating a satisfactory simulation.(2) The competitive adsorption equilibrium data for the binary system of EA and EC onto a macroporous resin SP825 were tested through batch experiments and modeled using the extended Langmuir equation at different pH, ionic strengths and temperatures. For both EA and EC, the adsorption was enhanced with the increase of pH, ionic strength and temperature. The relative errors of the extended Langmuir model were within 20%, showing a good agreement between the experimental and the model-predicted data. Selectivity coefficients for adsorption of EA and EC onto SP825 were determined. The results suggested that the adsorption ability of SP825 for EA was little stronger than EC, and a higher KCA value was observed at pH 7.0 with the increase of ionic strength and temperature. Some thermodynamic parameters of EA and EC were also calculated. It can be seen that the adsorption of both EA and EC onto SP825 was a spontaneous, endothermic and entropy incresing physisorption process. Under the same experimental condition,△GA<△GC,△HA>△HC, ASA>△SC(3) On the basis of the results above, the breakthrough curves for adsorption of EM, EA and EC in the fixed-bed were measured under the optimum condition. EA was found to breakthrough later than EC, thus a 2-stepwise elution chromatography process was established for the separation of EA and EC. The mobile phase and the first step elution mode of the chromatography was determined. By eluting the column with 3% ethyl acetate solution at the flowrate of 0.5 BV·h-1 for 5BV in the first step,the purity of EA could reach 95.4% in product.(4) To improve the EA yield of the stepwise elution chromatography process, a double-column swing chromatography process was further proposed and optimized. The results showed that the new process could not only produce high quality EM products(EA: 95.2%, EC:2.3%, EB:2.5%), but also increase the EA yield of the whole process obviously(EA total yield:93.3%). With the new process, the effective seraration of EA and EC components was finally realized.(5) Since the fermentation broth contains a lot of impurities, such as color, protein, etc, the effect of pretreatment of fermentation broth using membrane filtration technology was investigated. As a result, the 50nm ceramic membrane was selected, for the average decolorization rate, the average deproteinization rate and the average EM yield rate of the filtrate was 54.2%,66.6% and 95.0%, respetively. After the membrane filtration, the fermentation broth was then qualified for the adsorption process by macroporous resins.(6) A complete set of separation process for recovering EA from fermentation broth was introduced, including adsorption, impurity washing, desorption and salification in the eluate. The technological conditions and its practical effect of each unit operation were studied and optimized. The borax buffer solution with pH 10.0 was chosen to wash impurities and the mixture of 50% acetone and 50% 0.40mol·L-1 NaOH solution was selected to regenerate the resins. Through the whole separation process, the content of EC in product could meet the requirement of high quality EM product with a total yield over 90%. Moreover, the saturated adsorption capacity of the regenerated resin was no less than 80% compared with that of the fresh resin.An innovative technology routine which can be applied to industrial production directly for separation and purification of EA from fermentation broth has been presented in this paper. The results of this research provides the experimental foundation for the design and development of large-scale industrial equipments and has an expansively prospect.
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