Eureka AIR delivers breakthrough ideas for toughest innovation challenges, trusted by R&D personnel around the world.

Method for preparing cefepime dihydrochloride monohydrate crystal

A technology for cefepime dihydrochloride and monohydrate, which is applied in the field of controlling the preparation of cefepime hydrochloride to generate specific hydrate crystals, and can solve the problems of reducing water content, failing to meet Chinese quality standards, and unable to guarantee crystals, etc.

Inactive Publication Date: 2008-06-18
SHENZHEN SALUBRIS PHARMA CO LTD +1
View PDF5 Cites 5 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] There is certain shortcoming in the above-mentioned method that adds organic solvent (acetone or ethanol) to separate out cefepime hydrochloride in aqueous solution
It cannot guarantee that every batch of crystals is cefepime dihydrochloride monohydrate
In individual cases, especially in the case of Example 7 of US Patent No. 5,391,729, the crystals are all dihydrate of cefepime dihydrochloride (water content about 6.5%), and the water content cannot be reduced by drying
The product at this time does not meet the Chinese quality standards for the variety

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Method for preparing cefepime dihydrochloride monohydrate crystal

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0030] Embodiment 1, the refining of cefepime dihydrochloride monohydrate

[0031]Add 150 g of cefepime dihydrochloride monohydrate (HPLC purity 98%, prepared according to the method in US 4910301) to 750 mL of methanol under stirring at room temperature, add an appropriate amount of activated carbon after 10 minutes, and stir for 20 minutes. Filter and wash the carbon residue with an appropriate amount of acetone-methanol 1:1 (v / v) mixed solution. Combine the filtrates and cool to 10-20°C. Add 6500 mL of acetone to the filtrate under stirring, and complete the addition within about 1 hour. Stirring was continued for 1 hour. Suction. The filter cake was washed with acetone and dried under vacuum at 40° C. to obtain about 140 g of white crystals of cefepime dihydrochloride monohydrate. HPLC purity 99.5%, water content 3.3% (K-F method), residual methanol 0.20%, residual acetone 0.35%.

Embodiment 2

[0032] Embodiment 2, prepare cefepime dihydrochloride monohydrate by cefepime monohydrochloride

[0033] 136 g of cefepime monohydrochloride (HPLC purity 97%, prepared according to the method in US 4910301) was added to 750 mL of methanol under stirring at room temperature, and 50 mL of 20% HCl was added after 10 minutes. Stir for 10 minutes, if there is any insoluble matter, filter it off. Then add 6500 mL of acetone to the solution, and add it within about 1 hour. Stirring was continued for 1 hour. Suction. The filter cake was washed with acetone and dried under vacuum at 40° C. to obtain about 130 g of white crystals of cefepime dihydrochloride monohydrate with an HPLC purity of 99%.

Embodiment 3

[0034] Embodiment 3, prepare cefepime dihydrochloride monohydrate by cefepime dihydrochloride dihydrate

[0035] Add 150g of cefepime dihydrochloride dihydrate (HPLC purity 98%, prepared by the method in US 5391729) under stirring at room temperature to the mixed solution of 150mL water and 900mL methanol, add an appropriate amount of activated carbon after 10 minutes, and stir for 30 minute. Filter and wash the carbon residue with an appropriate amount of acetone-methanol 1:1 (v / v) mixed solution. Combine the filtrates and cool to 10-20°C. Add 8500 mL of acetone to the filtrate under stirring, and complete the addition within about 1 hour. Stirring was continued for 1 hour. Suction. The filter cake was washed with acetone and dried under vacuum at 40° C. to obtain about 130 g of white crystals of cefepime dihydrochloride monohydrate with an HPLC purity of 99.5%.

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The invention relates to a preparation or purification method of cefepime dihydrochloride monohydrate. The invention is characterized in that acetone, ethanol or the mixed solution of acetone and ethanol at the random portion is added into the methanol solution containing cefepime dihydrochloride and then cefepime dihydrochloride monohydrate crystal is precipitated. The method can effectively avoid the formation of cefepime dihydrochloride dihydrate.

Description

technical field [0001] The invention relates to a preparation method of cephalosporin, in particular to a preparation process for controlling cefepime hydrochloride to generate specific hydrate crystals. Background technique [0002] Cefepime (I, cefepime) is a fourth-generation cephalosporin antibiotic for injection. It is a broad-spectrum antibacterial substance developed in 1982 (US 4,406,899) by the American Boomer-Squibb (BMS). [0003] Cefepime is a neutral inner salt with high water solubility, its structure is: [0004] [0005] The currently discovered cefepime hydrochloride (also known as "cefepime hydrochloride" or "cefepime hydrochloride") includes cefepime monohydrochloride (Example IV of US 4910301), amorphous Anhydrous cefepime dihydrochloride (Example 1 of US5095011), anhydrous cefepime dihydrochloride (Example V of US 4910301), cefepime dihydrochloride monohydrate (Example XI of US 4910301 and XII), unstable cefepime dihydrochloride dihydrate (Example ...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
IPC IPC(8): C07D501/46
Inventor 叶澄海谭端明
Owner SHENZHEN SALUBRIS PHARMA CO LTD
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com