Method for converting cefotaxime acid into sodium salt crystal

Abstract

The invention provides a crystallization method for concerting cefotaxime acid to sodium salt; the method comprises the steps: water, acetone and anhydrous sodium acetate are added into a three-necked bottle; cefotaxime acid is added into the three-necked bottle after the temperature is lowered; then, the mixture in the three-necked bottle is stirred to cause the mixture to dissolve; next, added with active carbon, stirred, filtered and washed with acetone; the filter liquor is combined, added with acetone by dripping and added with crystal seeds, crystallized, stirred, added with acetone by dripping again, cooled, crystallized, filtered, soaked and washed with acetone for twice and dried in vacuum to obtain cefotaxime sodium crystal. The crystallization method has the advantages of simple menstruum, simplicity and feasibility, low cost, good crystal forms, good mobility, easy sub-package, high clarity and good color grade, thus being suitable for large-scale promotion and application and having obvious economic benefits.

Description

technical field [0001] The invention belongs to the technical field of antibiotics, and more specifically relates to a method for crystallizing cefotaxime acid into sodium salt. Background technique [0002] Cefotaxime sodium (cefotaxime sodium) (I) is a third-generation cephalosporin, which has a wide antibacterial spectrum, stable and safe characteristics, because it has an aminothiazolyl-cis-methoxyiminoacetyl group to bind the cephalosporin skeleton The aminoacylated structure at the seventh position in the drug has antibacterial activity against G(-) bacillus and drug-resistant bacteria that is dozens or hundreds of times stronger than that of the first and second-generation cephalosporins, and has the characteristics of less nephrotoxicity. The price is relatively cheap, so it is the most widely used antibiotic variety in clinical practice. However, due to the poor stability of cefotaxime acid, degradation reactions may occur at the three parts of its phthalimide side...

AI Technical Summary

Problems solved by technology

However, due to the poor stability of cefotaxime acid, degradation reactions may occur at the three parts of its phthalimide side chain, β-lactam ring and acetic acid group, so thioxamic acid that has been placed for a long time will degrade to varying degrees , resulting in deeper color and lower content. Generally, thioxamic acid is recrystallized, and then sodium-transformed crystallization is performed. The existing sodium-transferred crystallization technology is mostly used in a small amount of water and organic solvents. After the cefotaxime acid and alkali react, dropwise Solvent, to separate out cefotaxime sodium, but because of the reasons such as solvent type, dosage, rate of addition, water quantity, etc., cefotaxime sodium crystal yield is lower, and quality is poor, for example, when the amount of water in the crystallization system is bigger, cefotaxime sodium Wall sticking and agglomeration are more likely to occur, and the crystallization process is difficult to control; for example, the particle size, looseness, and difficulty of crushing of the finished product are different with different solvents, and the temperature also has a certain impact on the finished product.