Preparation method for type I ceftezole sodium crystal

Abstract

The invention discloses a type I ceftezole sodium crystal and a preparation method thereof. The preparation method is characterized by comprising the following steps of mixing sodium salt solution with ceftezole acid to obtain an aqueous solution of ceftezole sodium, decolorizing with activated carbon and filtering; dropping the aqueous solution of ceftezole sodium in mixed solution of organic solvent I and water by stirring; when needle-like precipitates are found, reducing the stirring rotating speed and growing the crystal at room temperature; continuously dropping the organic solvent I and organic solvent II, growing the crystal at low temperature and raising the stirring rotating speed; filtering, flushing the crystal with the mixed solution of the organic solvent I and the water and performing vacuum drying to obtain the type I ceftezole sodium crystal. According to the preparation method for the type I ceftezole sodium crystal, provided by the invention, the single type I ceftezole sodium crystal with the advantages of high purity, high thermal stability, homogeneous particles and good inter-batch repeatability can be obtained, and important significance for improving the stability and the safety of the ceftezole sodium for injection is realized; in addition, the preparation method has the advantages of simple operation, easiness in control for conditions and suitability for batch production.

Description

technical field [0001] The invention belongs to the technical field of medicine, relates to a preparation process of ceftiazole sodium crystals, and in particular relates to a preparation method of type I ceftiazole sodium crystals. Background technique [0002] Ceftazole is a first-generation cephalosporin. The main component of its injection form is ceftazole sodium monohydrate. Ceftazole sodium for injection is white to pale yellow powder or crystalline powder. It is suitable for the treatment of sepsis, pneumonia, bronchial Inflammation, secondary infection of chronic respiratory diseases, peritonitis, pyelonephritis, cystitis, urethritis and other bacterial infectious diseases have good results; It is difficult to prepare high-purity ceftiazole sodium due to the increase of the active ingredient content; in some cases, the ceftiazole sodium crystal is unstable or the impurities in it are increased due to improper control of the production process, resulting in a decreas...

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Problems solved by technology

[0004] The prior art has disclosed a variety of preparation methods for ceftezole sodium crystals, but none of them can obtain a single type I ceftezole sodium crystal, and has defects such as complex operation or device, poor repeatability of the preparation process, or unsuitability for mass production. Mainly include: (1) The anion / cation exchange membrane electrodialysis method disclosed in the patent CN 102010431A, the anion and cation exchange time of the feed liquid is long, and the final feed liquid needs to be distilled to obtain the product. This method has a large volume of feed liquid and a long preparation cycle, and It is difficult to expand the production capacity in the aseptic operation environment in large-scale production; (2) as the method disclosed in the patent CN 102286001A, the material is dissolved in water and a single-component organic solvent, and finally the product is separated out by distilling the solvent. This method is the same as the above (1) The method in has similarities, all need to be distilled, the solvent in this method is the mixture of organic solvent and water, the control of parameters such as vacuum degree, temperature, distillation time in the distillation process is difficult to ensure that water and organic The ratio of solvent is the same, so it is difficult to ensure that the same quality product can be obtained between batches; (3) as the dissolution method disclosed in patent CN 102219795A and the freeze-drying method disclosed in patent CN 103271878A, etc., all rely on external force Crystals are separated out, without the process of free crystal growth, it is difficult to ensure that a product with uniform properties is obtained; (4) as mentioned in the patent CN 102775426A, isopropanol and ethanol are used as crystallization solvents, and type I products can be obtained by ultrasonic seeding, but The words "higher content" and "mainly a single crystal form" are mentioned many times in the data in the following text. It can be seen that this method cannot prepare a single type I crystal. Carefully observe the test data and find that it is consistent with the literature (Acta Pharmacologica, 2002.37(4): 275-279) in the type II crystal coincidence, and there is no more convincing X-ray powder diffraction data

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