Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Preparation technology of sugammadex sodium

A technology of sugammadex sodium and sodium hydride, applied in the field of preparation of sugammadex sodium, can solve the problems of small difference in polarity, small difference in molecular weight, and high content of impurities related to sugammadex sodium

Active Publication Date: 2019-03-08
BRIGHTGENE PHARMA
View PDF6 Cites 6 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

This route uses flammable and explosive products such as sodium hydride, and there are potential safety hazards in industrial scale-up production, and the obtained sugammadex sodium has a high content of related impurities
[0006] Adam, Julia M.; Bennett, D. etc. disclose another method for preparing sugammadex sodium in the literature Journal of Medicinal Chemistry (2002), 45 (9), 1806-1816. The method is gamma cyclodextrin Bromide to obtain brominated γ-cyclodextrin, react brominated γ-cyclodextrin with methyl 3-mercaptopropionate to obtain sugammadex methyl gluconate, and sugammadex methyl gluconate in aqueous sodium hydroxide solution Hydrolysis produces sugammadex sodium. Although this method avoids the use of flammable and explosive products such as sodium hydride, the purity of sugammadex sodium produced is only about 80%, and the whole process is relatively complicated.
[0007] Due to the presence of thioether bonds in the molecular structure of sugammadex sodium, the compound is unstable to oxygen and is easily oxidized during the purification process to form a series of oxidized impurities and disulfide impurities such as sulfoxide, sulfone, and disulfide. There are many impurities Produced on the side chain structure of the sugammadex sodium molecule, which is similar to the sugammadex sodium structure, with small polarity and molecular weight differences, and is difficult to remove

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
  • Preparation technology of sugammadex sodium
  • Preparation technology of sugammadex sodium
  • Preparation technology of sugammadex sodium

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0028] Preparation of γ-ICD

[0029] In a 2000mL three-neck flask, under nitrogen protection, add 160ml of DMF and triphenylphosphine (30.1g, 15eq), and add iodine (30.5g, 15.6eq), exothermic violently, control the temperature at 25±5°C, and stir for 10min. Add dry good γ-cyclodextrin (10 g, 7.7 mmol), after the addition is complete, raise the temperature to 70° C. and stir for reaction for 24 hours. Cool the reaction solution to 10°C, add sodium methoxide solution (3.1g sodium added to 50ml methanol), stir for 30min, then add methanol 800ml, add 500ml purified water, and filter the solid. Crude γ-ICD 18.5 g was washed with water (3 x 100 ml) and then with acetone (3 x 100 ml).

[0030] In a 500ml three-necked flask, under nitrogen protection, add 18.5g of γ-ICD, add 185g of DMF, raise the temperature to 70°C, add 125g of purified water dropwise, the dropwise addition is complete, a large amount of solids are washed out, naturally and slowly cool down, and stir at 25°C for 4 ...

Embodiment 3

[0038] Add 1900g of DMF under nitrogen protection, add 60% sodium hydrogen (36.7g, 0.92mol), add BHT (0.88g, 0.004mol), cool to -5°C, add dropwise 3-mercaptopropionic acid (46.3g, 0.44mol) DMF solution, control the temperature at -5±5°C, complete the dropwise addition, raise the temperature to room temperature and stir for 2 hours, then add the 6-perdeoxy-6-periodo-γ-cyclodextrin obtained in Example 1 (95.0g, 0.04 mol) in DMF solution, heated up to 45°C, and reacted for 12h. After the reaction was completed, cooled to 5°C, added dropwise 558g of purified water, and filtered to obtain a crude product.

[0039] Dissolve the crude product obtained in the previous step in 400g of water, add 150g of diatomaceous earth and 1.0g of activated carbon, stir at room temperature for 30min and filter, transfer the filtrate to a 2000ml three-neck flask, replace with nitrogen three times, add 1200g of DMF solution dropwise, and stir at room temperature for 3 hours More sodium dextrose wet pr...

Embodiment 4

[0042] Under the protection of nitrogen, add 1900g of DMF, add 60% sodium hydrogen (36.7g, 0.92mol), add BHT (0.44g, 0.002mol), cool to -5 ° C, dropwise add 3-mercaptopropionic acid (46.3g, 0.44mol) DMF solution, control the temperature at -5±5°C, complete the dropwise addition, raise the temperature to room temperature and stir for 2 hours, then add the 6-perdeoxy-6-periodo-γ-cyclodextrin obtained in Example 1 (95.0g, 0.04 mol) in DMF solution, heated up to 45°C, and reacted for 12h. After the reaction was completed, cooled to 5°C, added dropwise 558g of purified water, and filtered to obtain a crude product.

[0043] Dissolve the crude product obtained in the previous step in 400g of water, add 150g of diatomaceous earth and 1.0g of activated carbon, stir at room temperature for 30min and filter, transfer the filtrate to a 2000ml three-neck flask, replace with nitrogen three times, add 1200g of DMF solution dropwise, and stir at room temperature for 3 hours More sodium dextr...

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 provides a method for preparing sugammadex sodium, which is simple in technology, high in purity and high in yield. The method comprises the following step: enabling per(6-deoxy-6-iodo)gamma-cyclodextrin to react with 3-thiohydracrylic acid under the existence of sodium hydride and BHT (2,6-ditert butyl-4-methylphenol), thus obtaining per[6-deoxy-6-(2-carboxyl)sulfo]gamma-cyclodextrin sodium salt, thus the sugammadex sodium.

Description

technical field [0001] The invention belongs to the field of medicine preparation, and in particular relates to the preparation of sugammadex sodium. Background technique [0002] Sugammadex sodium is a new type of selective muscle relaxant antagonist, which can selectively bind amino carrier muscle relaxants and terminate their muscle relaxant effect. The drug is a modified γ-cyclodextrin, which consists of 8 adjacent glucose molecules forming a ring-shaped molecular structure with a lipophilic inner cavity with an optimal inner diameter for accommodating amino carrier molecules, such as rocuronium bromide. 8 negatively charged hydrophilic carboxyl side chains project outward from the edge of the cyclodextrin molecule, and the acidic functional group (COO—) on the side chain increases the lipophilicity of the inner cavity of sugammadex sodium and can bind with Roku The positively charged nitrogen atoms of ammonium bromide form electrostatic bonds. At the same time, these ...

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): C08B37/16
CPCC08B37/0012
Inventor 袁建栋黄仰青池建文葛亮
Owner BRIGHTGENE PHARMA
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap 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