Synthesis of antibiotic ceftazidime, ceftazidime for injection and preparation method of ceftazidime

A technique for ceftazidime and its synthetic method, which is applied in the field of antibiotic drug preparation, can solve the problems of ceftazidime, such as difficult and accurate quantification, large particle size, and uneven mixing, and is suitable for large-scale industrial production, with low impurity content and good fluidity Effect

Inactive Publication Date: 2013-01-16
国药集团致君(苏州)制药有限公司 +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Ordinary ceftazidime for injection is made by mixing ceftazidime and pharmaceutical excipients in aseptic packaging. There are large particle sizes,

Method used

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  • Synthesis of antibiotic ceftazidime, ceftazidime for injection and preparation method of ceftazidime
  • Synthesis of antibiotic ceftazidime, ceftazidime for injection and preparation method of ceftazidime
  • Synthesis of antibiotic ceftazidime, ceftazidime for injection and preparation method of ceftazidime

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0042] Synthesis of TA (7-PyCA)

[0043] Into the flask, add 55g of 7-ACA, 45g of hexamethyldisilane, and 1ml of activator trimethylchlorosilane, control the temperature at 40°C~50°C, and keep the reaction for 4 hours to obtain compound 1.

[0044] To compound 1, 65 g of iodotrimethylsilane was slowly added dropwise over 50 to 60 minutes, the addition temperature was controlled at 12°C to 15°C, and the reaction was kept for 2 hours to obtain compound 2.

[0045]In the flask, 35 g of pyridine was slowly added dropwise over 40 to 45 minutes, the temperature was controlled at 3°C ​​to 5°C, and the reaction was kept for 1 hour to obtain compound 3.

[0046] To compound 3, slowly add 45g of methanol dropwise over 60 minutes, control the temperature at 10°C~15°C, add a mixed solution consisting of 100g of hydrochloric acid and 100g of water, stir for 30 minutes, carry out crystal growth for 30 minutes, and continue stirring for 2 hours to obtain compound TA (7-PyCA), the mass yield...

Embodiment 2

[0054] Synthesis of TA (7-PyCA)

[0055] Into the flask, add 55g of 7-ACA, 45g of hexamethyldisilane, and 1ml of trimethylchlorosilane as an active agent, control the temperature at 20°C to 30°C, and keep the reaction for 4 hours to obtain compound 1.

[0056] To compound 1, 65 g of iodotrimethylsilane was slowly added dropwise over 50 to 60 minutes, the addition temperature was controlled at 10°C to 11°C, and the reaction was kept for 2 hours to obtain compound 2.

[0057] In the flask, 35 g of pyridine was slowly added dropwise over 40 to 45 minutes, the temperature was controlled at 0°C to 3°C, and the reaction was kept for 1 hour to obtain compound 3.

[0058] To compound 3, slowly add 45g of methanol dropwise over 60 minutes, control the temperature at 0°C~5°C, add a mixed solution consisting of 100g of hydrochloric acid and 100g of water, stir for 30 minutes, grow crystals for 30 minutes, and continue stirring for 2 hours to obtain compound TA (7-PyCA), the mass yield w...

Embodiment 3

[0066] Synthesis of TA (7-PyCA)

[0067] Into the flask, add 55g of 7-ACA, 45g of hexamethyldisilane, and 1ml of trimethylchlorosilane as an active agent, control the temperature at 60°C to 80°C, and keep the reaction for 4 hours to obtain compound 1.

[0068] To compound 1, slowly add 65 g of iodotrimethylsilane dropwise over 50 to 60 minutes, control the feeding temperature at 15°C to 20°C, and keep the reaction for 2 hours to obtain compound 2.

[0069] In the flask, 35 g of pyridine was slowly added dropwise over 40 to 45 minutes, the temperature was controlled at 8°C to 10°C, and the reaction was kept for 1 hour to obtain compound 3.

[0070] To compound 3, slowly add methanol 45g dropwise over 60 minutes, control the temperature at 15°C~20°C, add a mixed solution consisting of 100g hydrochloric acid and 100g water, stir for 30 minutes, carry out crystal growth for 30 minutes, and continue stirring for 2 hours to obtain compound TA (7-PyCA), the mass yield was 1.29%.

...

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Abstract

The invention discloses synthesis of antibiotic ceftazidime, ceftazidime for injection and a preparation method of ceftazidime. 7-ACA is served as a raw material, silanization and iodo reaction are carried out, and pyridine, hydrochloric acid and water are added to obtain TA (7-PyCA); ceftazidime active ester is added in an organic solvent and an inorganic solvent to obtain new modified ceftazidime active ester; TA is added in new modified ceftazidime active ester, organic mixed solvent and triethylamine are added, then acid water and an acetone solution are added to obtain TC (ceftazidime dihydrochloride), and ceftazidime is obtained through the reaction. The synthesis of ceftazidime provided by the invention has the advantages that ceftazidime is high in yield, operation processes are simplified, production cost is low, ceftazidime is applicable to industrial production, obtained products can be stored for a long time, a structure is stable, and impurity content is low. Ceftazidime for injection has the advantages of being moderate in grain size, good in clarity, less in impurity content, excellent in quality, stable and the like, and is high in split charging efficiency in production, good in content uniformity, high in medicine dissolution rate in clinical application and good in dissolubility.

Description

technical field [0001] The invention belongs to the field of antibiotic drug preparation, in particular to the synthesis of an antibiotic ceftazime, ceftazidime for injection and a preparation method thereof, belonging to the field of antibiotic drug preparation. Background technique [0002] Ceftazidime (Ceftazidime) is the third-generation cephalosporin created by GlaxoSmithKline. It was approved by the FDA in July 1985. The chemical name of Ceftazidime is: (6R,7R)-7-[[(2-Amino-4- Thiazolyl)-[(1-carboxy-1-methylethoxy)imino]acetyl]amino]-2-carboxy-8-oxo-5-thia-1-azabicyclo[4.2.0 ] Oct-2-ene-3-methylpyridinium inner salt pentahydrate, its structural formula is as follows: [0003] [0004] Ceftazidime has the following characteristics: 1. Extended-spectrum third-generation cephalosporin; 2. It has the strongest anti-Pseudomonas aeruginosa activity and is currently the first choice for the treatment of Pseudomonas aeruginosa infection; 3. The first choice and recommended...

Claims

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Application Information

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IPC IPC(8): C07D501/46C07D501/06A61K31/546A61P31/04
Inventor 黄凯施桂山史利军胡朝新杨磊
Owner 国药集团致君(苏州)制药有限公司
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