以苯系和萘系化合物为络合剂，研究头孢氨苄结晶母液中头孢氨苄的富集回收过程，考察了络合剂种类、剂量、pH、温度、残留原料和副产物浓度对头孢氨苄络合过程的影响，确定了关键影响因素，建立和优化了工艺过程. 结果表明，络合剂种类、剂量和pH是影响头孢氨苄络合率的关键因素，其它因素对头孢氨苄络合率无明显影响. 最佳络合工艺为1-萘酚剂量4.4 g/L，pH为4.72，温度293 K，此时头孢氨苄的络合率大于97.0%，比目前生产工艺提高了5.0%.
Cephalexin (CEX) was a widely used antibiotic in clinic. The proportion of CEX in crystalline mother liquor was about 10%, which must be recovered in order to decrease economic losses, environmental pollution and prevent the rise of drug-resistant bacteria. The preparation of CEX by enzymatic-catalyzed is a green pharmaceutical technology, but recovery of CEX from the crystalline mother liquor had not been studied systematically. In this work, the recovery of CEX in the crystalline mother liquor by enzymatic-catalyzed preparation was investigated with benzene and naphthalene compounds as complexing agents. The effect factors including complexing agent type, complexing agent dosage, pH, temperature, concentration of residual raw materials and by-product on CEX complexation process were systematically studied, and an optimization scheme was proposed. The results showed that CEX complexation rate was higher using naphthalene compounds as complexing agents than that of benzene compounds. The type of complexing agent and its dosage, pH were key factors on CEX complexation rate, while the temperature, concentration of residual raw materials and main by-product, such as 7-amino-3-desacetoxicephalosporanic acid (7-ADCA), phenylglycine methyl ester hydrochloride (PGME) and phenylglycine (PG) had no significant effect on CEX complexation rate. The optimum parameters were as follows: 1-naphthol dosage of 4.4 g/L, pH of 4.72 and temperature of 293 K. Under the optimal conditions, the CEX complexation rate was more than 97.0%, which increased by 5.0% compared to that in the conventional industrial process. Using dichloromethane as a decomplexing agent, the total recovery rate of CEX was more than 92%. Furthermore, the CEX products were analyzed by HPLC, the content of CEX, 1-naphthol were 98.5% and 0.009%, respectively. While the impurities in the CEX products, such as 7-ADCA, PGME and PG were not detected. The quality of CEX products conformed to Chinese pharmacopeia standard. This work suggested an effective approach for CEX recovery and pollutions decrease.
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