Method for producing aztreonam amino acid salt

A technology of amino acid salt and aztreonam, which is applied in the field of preparation of aztreonam amino acid salt, can solve the problems of low reaction yield, long freeze-drying process, low water solubility of aztreonam, etc., and achieve high reaction yield, Simple operation, good water solubility

Inactive Publication Date: 2008-05-07
PKU HEALTHCARE CORP LTD
View PDF3 Cites 12 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0009] In order to solve the problem of low water solubility of aztreonam, Chinese patent CN1030238 discloses a mixture of preparing aztreonam L-arginine, which is to mix L-arginine and aztreonam, then dissolve it in water and The mixture of L-arginine and aztreonam is obtained by freeze-drying, but there are high investment and operating costs for freeze-drying equipment, long freeze-drying process, high product cost, and problems such as uneven moisture content
[0010] Document WO2005 / 005424 reports a method for preparing aztreonam lysine salt, which is prepared by dissolving aztreonam in water, and then adding an aqueous solution of lysine dropwise. The preparation process of this method is simple and no special equipment is required. Because aztreonam lysine salt has poor stability in aqueous solution, it is partially decomposed into aztreonam and lysine, so that the reaction yield is not high, less than 70%.
[0011] The more common problem of the above methods is that aztreonam salt is not made, but it is directly mixed for medicinal purposes, or it is mixed and then freeze-dried to obtain its mixture, or its lysine salt is obtained in water. The yield is not high

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 producing aztreonam amino acid salt

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0030] Embodiment 1: the preparation of aztreonam arginine salt

[0031] Step (1): Prepare aztreonam solution

[0032] Get 20.0 grams of aztreonam crude product (moisture content 12.5%) and be dissolved in 350ml ethanol and stand-by;

[0033] Step (2): Preparation of L-arginine solution

[0034] Get 14.0 grams of L-arginine and dissolve it in water to make a 15% aqueous solution for later use;

[0035] Step (3): Preparation of aztreonam arginine salt

[0036] Add the aqueous amino acid solution in step (2) dropwise to the aztreonam solution in step (1) until the pH of the reaction solution is 4.5, react for 1 hour at 0°C, cool the resulting reactant, filter, After drying, 23.7 g of the obtained aztreonam arginine salt was obtained, and the yield was 70.7%.

Embodiment 2

[0037] Embodiment 2: the preparation of aztreonam lysine salt

[0038] Step (1): Prepare aztreonam solution

[0039] Get 25.0 grams (moisture content 14.3%) of aztreonam crude product and be dissolved in 150ml ethanol for stand-by;

[0040] Step (2): Preparation of L-lysine solution

[0041] Get 15.5 grams of L-lysine and dissolve in water to prepare a 24% aqueous solution for use;

[0042] Step (3): preparation of aztreonam lysine salt

[0043] Add the aqueous solution of lysyl acid in step (2) dropwise to the aztreonam solution in step (1), until the pH value of the reaction solution is 5.5, react for 120 minutes at 20°C, and cool the reactant obtained, After filtering and drying, 28.5 g of the obtained aztreonam lysine salt was obtained, and the yield was 72.0%.

Embodiment 3

[0044] Embodiment 3: the preparation of aztreonam arginine salt

[0045] Step (1): Prepare aztreonam solution

[0046] Get 45.0 grams (moisture content 11.5%) of aztreonam crude product and be dissolved in 270ml methanol for stand-by;

[0047] Step (2): Preparation of L-arginine solution

[0048] Get 31.9 grams of L-arginine and dissolve in water to prepare a 34% solution for use;

[0049] Step (3): Preparation of aztreonam arginine salt

[0050] Add the above L-arginine aqueous solution dropwise to the aztreonam solution until the pH value of the reaction solution is 4.7, react for 2 hours at 40°C, cool, filter, and dry to obtain aztreonam arginine Salt 65.3g, the yield is 91.0%.

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 discloses a synthesis method for aztreonam salt. The method comprises the steps as follow: aztreonam is dissolved into organic solvent; the water solution of amino acid is dropped in the mixture; and the aztreonam salt is obtained by cooling and filtering the solution after full reaction. The invention is characterized in that the organic solvent is used as reaction solution, thereby ensuring the salt making reaction of aztreonam to be more completely with the high reaction yield; the used solvent can be recycled, thereby enabling the aztreonam amino acid salt to have better water-solubility and to be more easily to be made into preparations; and the salt is no longer mixed with the amino acid, thereby being more convenient for medicine use. The invention has the advantages of easy operation, high purity, low cost, and being suitable for mass production.

Description

technical field [0001] The invention relates to a preparation method of antibacterial drugs, in particular to a preparation method of aztreonam amino acid salt. Background technique [0002] Aztreonam is a new monocyclic β-lactam antibiotic first developed by Bristol-Myers Squibb in the United States. It was first launched in Italy in 1984, and then in many European and American countries. It is the first monocyclic β-lactam antibiotic used clinically. It is currently used clinically well, and its curative effect is very affirmed at home and abroad. [0003] The chemical name of aztreonam is: [2s-[2α, 3β(Z)]]-2-[[[1-(2-amino-4-thiazolyl)-2-[(2-methyl-4- Oxo-1-sulfo-3-azetidinyl)amino]-2-oxoethylene]amino]oxo]-2-methylpropionic acid, and has the following chemical structure: [0004] [0005] Its pharmacological action is as follows: aztreonam inhibits the fusion of the cell wall through a high affinity with penicillin-binding protein 3 (PBP3) on the cell membrane of sen...

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
Patent Type & Authority Applications(China)
IPC IPC(8): C07D417/12
Inventor 张金生马世宁李明川
Owner PKU HEALTHCARE CORP 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
Try Eureka
PatSnap group products

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

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap