Study Of Resin Adsorption-Two Steps Crystallization To Separate And Purify Kelimycin

Kelimycin, obtained by fermentation, is a kind of macrolide antibiotics comprising with various components. The downstream separation process is the key to produce Kelimycin. Solvent extraction is the present separation method but it has no selectivity between components and impurities. In addition, there is serious emulsion during operation, which affects yield and product quality. Therefore, this paper developed a new Kelimycin separation process, which consisted of macro-resin adsorption and two-steps crystallization. The specific process was about:after filtrated by inorganic membrane and concentrated by nano-membrane, the Kelimycin fermentation broth was adsorbed by macroporous resin HZ820. The pigments also adsorbed in resin were washed out by Ethanol-alkaline buffering solution. The main components were desorbed by butyl acetate and washed by acid solution. Then extraction transferred Kelimycin main components to aqueous phase. The product was finally obtained by two steps crystallization.The research turned out that:(1) Adams-Bohart was a good model to fit the resin fixed bed adsorption process. When the amount of adsorption accounted for60%of the saturated, the yield of Kelimycin reached at least97%if feed was controlled at an appropriate rate regarding different concentrations.(2) Around67%pigment was washed out by using ethanol-pH9.0, NaH2PO4(25%volume fraction for ethanol) mixture solution. Subsequent elution by butyl acetate at rate of2BV/h made yield of effective components reach98%.(3) The strong polar impurities were preferably removed by using0.7%NaH2PO4buffer solution to wash ester phase. Then Kelimycin was extracted to aqueous phase in NaH2PO4-H3PO4system. The weak polar impurities were preferably removed when extraction pH=4.4. Alkali solution was added to extraction phase to make Kelimycin lose combined H+to crystallize. Because weak polar impurities were more easily to lose H+and crystallize, two-steps of crystallization was created and weak polar impurities were enriched in the first step. Then the second step product can meet the drug quality. Under the condition of25℃, the best step pH was7.2.This paper developed a new process for separating and purifying Kelimycin. The product components were optimized by the combined unit operations of resin adsorption, desorption, washing, extraction and two-steps crystallization. The quality was controlled by adjusting process parameters. Finally the yield of qualified Kelimycin product reached at31%.