Ceftizoxime sodium preparation and refining method

A technology of ceftizoxime sodium and ceftizoxime acid, which is applied in the field of drug synthesis, can solve problems such as difficult drying, poor product color, complicated operation, etc., and achieve the effects of ensuring drug safety, improving product quality, and simple operation

Active Publication Date: 2013-02-06
TIANJIN GREENPINE PHARMA
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Problems solved by technology

However, the amount of anhydrous sodium carbonate has a great influence on the reaction time and product quality. When the amount of anhydrous sodium carbonate is increased, the reaction time is obviously shortened, but the content of ceftizoxime sodium in the product is obviously decreased, and the impurity content is correspondingly increased. The color is also significantly worse; and the resulting product easily contains undissolved sodium bicarbonate, which affects product quality
The Journal of Shanxi Medical University published an article titled "Research on the Synthesis of Ceftizoxime Sodium", which mentioned that ceftizoxime acid was dissolved in water, triethylamine was added dropwise and stirred to dissolve, after activated carbon was decolorized, sodium isooctanoate was added dropwise. Ethanol solution, after adjusting the pH, add ethanol dropwise, crystallize to obtain ceftizoxamic acid, the resulting product contains ethanol and is not easy to dry
Chinese patent CN101348492 discloses a method for preparing high-purity ceftizoxime sodium. It is intended to convert ceftizoxime sodium into ceftizoxime acid in water, extract the crude product of ceftizoxime acid with an organic reagent, and use an aluminum peroxide chromatography column to remove the resulting The solvent in the mobile phase is dissolved by adding a lower alcohol, and the product is extracted by adding an alkali. This method uses an alumina chromatography column, and a large amount of eluent is used, which is costly, pollutes the environment, and is complicated to operate. It is not suitable for industrial production.

Method used

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  • Ceftizoxime sodium preparation and refining method

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Embodiment 1

[0017] Synthesis of Ceftizoxime Sodium (Ⅰ)

[0018] In a 100ml reaction flask, add 25ml of deionized water, cool to 5-10°C, add 12.6g (0.03mol) of ceftizoxime acid, add 6.0g (0.036ml) of sodium isooctanoate in batches with stirring, and stir for 1.5h When the reaction is complete, add 0.2g activated carbon to decolorize, filter with suction, wash with a small amount of water, pour the filtrate into a 250ml reaction flask, adjust the pH to 7, at 20-25℃, slowly add 150ml of acetone to the filtrate, stir and crystallize. After suction filtration, the filter cake was washed with acetone, and after drying, 10.7 g of ceftizoxime sodium was obtained with a yield of 88.3% and a purity of 99.3% by HPLC normalization.

Embodiment 2

[0020] Refining of Ceftizoxime Sodium (Ⅰ)

[0021] At room temperature, add 20ml of purified water to a 100ml reaction flask, add 10g of ceftizoxime sodium, stir to dissolve, add 0.2g activated carbon, stir for 30min, filter with suction, wash with a small amount of water, pour the filtrate into a 250ml reaction flask, stir under Bottom, slowly add 120ml of acetone, stir for 1-2h, filter, wash with acetone, and dry to obtain 9.5g of ceftizoxime sodium with higher purity, with a yield of 95%. Product purity ≥99.5% (HPLC).

[0022] Elemental analysis:

[0023] Theoretical value: C: 38.52% H: 2.98% N: 17.27% O: 19.73% S: 15.81%

[0024] Measured value: C: 38.48% H: 2.97% N: 17.25% O: 19.75% S: 15.86%

[0025] 1H-NMR(DMSO-d6) δ: 3. 35 (2H, m), 3. 47 (3H, s), 4.95 (1H, d, J = 3. 9 Hz), 5. 62 (1H, dd, J = 3. 8 Hz, 6. 6Hz), 5. 96 (1H, m), 6. 71 (1H, s), 7. 23 (2H, s), 9.51 (1H, d, J = 6 . 6 Hz). Theoretical value: C: 38.52% H: 2.98% N: 17.27% O: 19.73% S: 15.81%

[0026] Measured value: C:...

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Abstract

The invention relates to a ceftizoxime sodium preparation and refining method through utilizing ceftizoxime acid. The method comprises the following steps: producing product-ceftizoxime sodium through utilizing the ceftizoxime acid by the action of a salt forming agent; achieving the purposes of refining and purifying through recrystallization; and finally obtaining high purityceftizoxime sodium. According to the invention, the product quality of API is improved, the toxic side effect is reduced, and safety is ensured during preparation of anti-bacterial medicines. Compared with the prior art, the method has the advantages of high product purity, simplicity and convenience in operation, low cost, high yield, reduced toxic side effect, and suitability for industrialized production.

Description

Technical field [0001] The invention belongs to the technical field of drug synthesis, and relates to a method for preparing cephalosporin drugs, and more specifically to a method for preparing ceftizoxime sodium. Background technique [0002] Ceftizoxime sodium, English name: Ceftizoxime Sodium, chemical name: (6R, 7R)-7-[(Z)-2-(2-amino-4-thiazolyl)-2-methoxyiminoacetamide Base] -8-oxo-5-thia-1-aminobicyclo[4.2.0]oct-2-ene-2-carboxylic acid sodium salt, molecular formula: C13H12N5NaO5S2, molecular weight: 405.38, structural formula: [0003] [0004] Ceftizoxime sodium is a third-generation cephalosporin antibiotic developed by Fujisawa Pharmaceutical Co., Ltd. in Japan. It was first marketed in Japan in 1982 under the trade name Ceftizox. As a third-generation cephalosporin antibiotic, this product has a bactericidal effect by inhibiting the biosynthesis of bacterial cell wall mucopeptides. It has the characteristics of broad-spectrum, high efficiency, enzyme resistance, low to...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D501/20C07D501/04
Inventor 沈载宽郑林海
Owner TIANJIN GREENPINE PHARMA
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