Cefoperazone compound pharmaceutical preparations and new indications for the treatment of endometritis and other gynecological reproductive tract infections

A cefoperazone sodium, reaction technology, applied in the field of drug preparation, can solve problems such as allergic reaction, polymer increase, pharmacological hazards, etc.

Active Publication Date: 2021-05-18
广东金城金素制药有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0020] Due to the injection of cefoperazone sodium, many adverse reactions have also occurred
Although cefoperazone sodium injection is a sterile preparation, which greatly reduces the occurrence of adverse reactions, due to cefoperazone sodium remaining or introducing impurities in the synthesis, purification and preparation of preparations, it will cause the stability of cefoperazone sodium to deteriorate, polymers will increase, and eventually lead to allergic reactions. occur
In addition, some impurities can also cause pharmacological hazards to the human body, which is not conducive to human health.

Method used

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  • Cefoperazone compound pharmaceutical preparations and new indications for the treatment of endometritis and other gynecological reproductive tract infections
  • Cefoperazone compound pharmaceutical preparations and new indications for the treatment of endometritis and other gynecological reproductive tract infections
  • Cefoperazone compound pharmaceutical preparations and new indications for the treatment of endometritis and other gynecological reproductive tract infections

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0108] The synthesis of embodiment 1 cefoperazone sodium

[0109] Step 1), 272g (1.0mol, M=272.28) 7-ACA, 122g (1.05mol, M=116.14) MTT were dissolved in acetonitrile (820mL) containing 83.1g pyridine (1.05mol, M=79.10), cooling to 5°C, add 208.6g TiCl 4 (1.1 mol, M=189.68)—37.4 g tetrabutyl titanate (0.11 mol, M=340.3) catalyst, heat up to 30° C., and react for 3 h under stirring. After the reaction, filter, cool the filtrate to 0-5°C, add 10% ammonia water dropwise to the isoelectric point under stirring, crystallization occurs, continue to stir for 1h, filter with suction, wash with acetone, and dry to obtain a white solid powder 7-ACT ( M=328.37) 327.4g, yield 98.0%, HPLC content greater than 98.3%.

[0110] Step 2): Dissolve 353.8g of oxypiperazine acid chloride (1.0mol, M=353.76) in 1100mL of N,N-dimethylformamide, stir and cool to -20°C. Dissolve the prepared 7-ACT in 1100mL N,N-dimethylformamide, add 34mL trimethylchlorosilane under ice-bath cooling to remove the mo...

Embodiment 2

[0115] The synthesis of embodiment 2 cefoperazone sodium

[0116] The same as the synthesis process of Example 1, the only difference is: in step 1), in step 1), MTT 139.4g (1.20mol), that is, the molar ratio of 7-ACA and MTT is 1:1.20.

Embodiment 3

[0117] The synthesis of embodiment 3 cefoperazone sodium

[0118] The same as the synthesis process of Example 1, the only difference is: in step 1), in step 1), MTT 151g (1.30mol), that is, the molar ratio of 7-ACA and MTT is 1:1.30.

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Abstract

The invention discloses a new indication for treating endometritis and other gynecological reproductive tract infections with a medicinal preparation of safa and cefoperazone. The cefoperazone sodium provided by the invention through a specific raw material production process has extremely low impurity content and significant drug efficacy, which is beneficial to improving the quality of the preparation product, ensuring the safety and effectiveness of the preparation product, and has the advantages of preparing and treating endometritis and other gynecological reproductive tract infections. Drug use.

Description

technical field [0001] The invention relates to medicine preparation technology, in particular to a new indication for treating endometritis and other gynecological reproductive tract infections with a pharmaceutical preparation of Saifa and cefoperazone. Background technique [0002] Cefoperazone sodium (Cefobid, C 25 h 26 N 9 NaO 8 S 2 ), which are third-generation cephalosporins. The chemical name is 7-(((4-ethyl-2,3-dioxo-1-piperazinyl)formylamino)(4-hydroxyphenyl)acetamido)-3-((1-methyl -1H-tetrazol-5-yl)thiomethyl)-8-oxo-5-thio-1-azabicyclo(4.2.0)oct-2-ene-2-carboxylic acid sodium salt. Its chemical structural formula is as follows: [0003] [0004] Cefoperazone sodium, listed by Pfizer (Pfizer) in 1988, the current Brand Name of this product: Pioneer must CEFOBID, is the third generation of cephalosporin antibiotics, its antibacterial mechanism is by inhibiting the production of sensitive bacterial cell wall mucopeptides during the bacterial reproduction pe...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D501/04C07D501/36A61K31/546A61K31/43A61K31/431A61K31/438A61K31/551A61K45/06A61P15/00A61P31/04
CPCA61K31/43A61K31/431A61K31/438A61K31/546A61K31/551A61K45/06A61P15/00A61P31/04C07D501/04C07D501/36A61K2300/00
Inventor 薛晓斌傅苗青周白水王丽霞吴丰喆马庆双俞玉萍李秋荣应鹏
Owner 广东金城金素制药有限公司
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