Study On The Separation And Purification Process Of Tobramycin

Tobramycin(TOB)is an aminoglycoside antibiotic,and which is produced by Streptomyces tenebrarius.It is active against a broad spectrum of Gram-negative bacteria.TOB is particularly indicated for the treatment of septicemia,complicated and recurrent urinary tract infections,lower respiratory infections,ophthalmic and central nervous system infections,serious skin and soft tissue infections including burns and peritonitis.Compared with gentamycin,tobramycin has obvious inhibitory effect on Pseudomonas aeruginosa,and which has less nephrotoxicity encountered during its clinical use.TOB and kanamycin B are produced after base catalyzed hydrolysis of nebramine,TOB was less hydroxyl on the structure than kanamycin B,it is hard to separate them.At present,tobramycin is purified with weak acid cationic resin,every step of purification will result in the loss of tobramycin,which increase the production cost and reduce the recovery rate.This paper will discuss the new process that use minimal purification steps to achieve desired yield and purity.To develop the separation and purification processes of tobramycin with mixed resins.Based on adsorption capacity and desorption capacity of resin and the purity of tobramycin,HZ-3C and JK110 were selected from ten types of resin as the effective adsorbent for separation and purification of tobramycin.Sorption equilibrium was attained within 50 min.Adsorption kinetics of JK110 followed Pseudo-first-order rate equation.The pseudo-second order kinetics model yielded the best fit for the experimental data of HZ-3C sorption kinetics.The adsorption isotherms were well-fitted into the Langmuir isotherm models.The purification conditions were specified as the following:the ratio of HZ-3C and JK110 was 3:1,the pH value was 9,the flow rate was 3BV/h,The optimum desorption conditions was obtained by gradient elution with 0.3%and 0.7%Ammonia water,Under these conditions,tobramycin content were increased from 32.85%to 94.82%,with a tobramycin recovery rate of 88.26%.D401-Cu(II)with high performance of adsorption and desorption of tobramycin was selected from 4 different types of D401-M(II)and establish the optimum technological conditions.In static state,the best pH value was 9.8,Adsorption kinetics followed Pseudo-second-order rate equation.The adsorption equilibrium was well fitted by Langmuir formula.In dynamic state,the optimum adsorption conditions were specified as the flowings:the highest recovery ratio can be reached at the radio of 1 to 1(D401-Cu(II)to D401),the concentration of sample solution and flow rate were 5.76mg/mL and 4BV/h.The optimum desorption conditions was obtained by gradient elution with 0.3%and 0.7%Ammonia water,elution volume were 6BV,respectively.Under these conditions,tobramycin content were increased from 32.85%to 92.18%,with a tobramycin recovery rate of 97.46%.The results showed that D401-Cu(II)could be used in separation and purification for tobramycin.