Bi-functional polyethylene glycol derivative and preparation method thereof

A polyethylene glycol and bifunctional technology, which is applied in the field of bifunctional polyethylene glycol derivatives and their preparation, can solve the cumbersome protection and deprotection of functional groups, the high price of polyethylene glycol derivatives, the Problems such as the decrease of the molecular weight of alcohols, etc., to achieve the effects of mass production, mild reaction conditions, high yield and product purity

Inactive Publication Date: 2013-09-25
XI AN JIAOTONG UNIV
View PDF7 Cites 20 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The Chinese patent application number 200910023552.3 discloses a preparation method for oxidizing polyethylene glycol terminal hydroxyl groups to terminal carboxyl groups by using potassium permanganate, but this potassium permanganate oxidation method is likely to cause the molecular weight of polyethylene glycol to decrease, increase Uncertainty about the follow-up response
In addition, the preparation process of some polyethylene glycol derivatives, such as heteromeric polyethylene glycol derivatives, also involves cumbersome processes such as protection and deprotection of functional groups.
These are the main reasons for the high price of polyethylene glycol derivatives

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
  • Bi-functional polyethylene glycol derivative and preparation method thereof
  • Bi-functional polyethylene glycol derivative and preparation method thereof
  • Bi-functional polyethylene glycol derivative and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0043] 1) Synthesis of 3,3'-dithiodipropionylhydrazide:

[0044] Add 3,3'-dithiodipropionic acid and ethanol to a reactor containing toluene and p-toluenesulfonic acid, reflux for 10 hours, remove the solvent in a vacuum, and then add a mass concentration of 50% hydrazine hydrate aqueous solution, reflux reaction for 3 hours, and then recrystallized with a solvent mixed with water and ethanol at a volume ratio of 3:7 to obtain 3,3'-dithiodipropionyl hydrazide; wherein, the The molar ratio of added 3,3'-dithiodipropionic acid to ethanol is 1:15, and the molar ratio of 3,3'-dithiodipropionic acid to hydrazine hydrate in aqueous solution is 1:20; 3 , The molar ratio of 3'-dithiodipropionic acid to p-toluenesulfonic acid is 1:0.005; add 0.6mol of 3,3'-dithiodipropionic acid per liter of toluene;

[0045] 2) Synthesis of 2,2'-dithiodiethylisocyanate:

[0046] Dissolve 3,3'-dithiodipropionylhydrazide in hydrochloric acid with a concentration of 3mol / L, add dropwise an aqueous solu...

Embodiment 2

[0054] 1) Synthesis of 2,2'-dithiodiacetylhydrazide:

[0055] Add 2,2'-dithiodiacetic acid and methanol into a reactor containing toluene and p-toluenesulfonic acid, reflux for 8 hours, remove the solvent in a vacuum, and then add a mass concentration of 65 to the residue in the reactor % hydrazine hydrate aqueous solution, reflux reaction for 5 hours, and then recrystallized with a solvent mixed with water and ethanol at a volume ratio of 2:8 to obtain 2,2'-dithiodiacethydrazide; wherein, the added 2 , The molar ratio of 2'-dithiodiacetic acid to methanol is 1:15, the molar ratio of 2,2'-dithiodiacetic acid to hydrazine hydrate in aqueous solution is 1:30, 2,2'-di The molar ratio of thiodiacetic acid to p-toluenesulfonic acid is 1:0.01; add 1mol of 2,2'-dithiodiacetic acid to every liter of toluene;

[0056] 2) Synthesis of dithiodimethylisocyanate:

[0057] Dissolve 2,2'-dithiodiacetylhydrazide in hydrochloric acid with a concentration of 3mol / L, add dropwise sodium nitrit...

Embodiment 3

[0063] 1) Synthesis of 4,4'-dithiodibutyrhydrazide:

[0064] Add 4,4'-dithiodibutyric acid and methanol into a reactor filled with toluene and concentrated sulfuric acid with a mass concentration greater than 95%, reflux for 6 hours, remove the solvent in a vacuum, and add to the residue in the reactor Add an aqueous solution of hydrazine hydrate with a mass concentration of 85%, and then reflux for 6 hours, and then recrystallize with a solvent mixed with water and ethanol at a volume ratio of 1:9 to obtain 4,4'-dithiodibutyric hydrazide ; Wherein, the molar ratio of added 4,4'-dithiodibutyric acid to methanol is 1:25, and the molar ratio of 4,4'-dithiodibutyric acid to hydrazine hydrate in aqueous solution is 1 :25,4,4'-dithiodibutyric acid and the mol ratio of concentrated sulfuric acid are 1:0.015; Add 1.5mol of 4,4'-dithiodibutyric acid in every liter of toluene;

[0065] 2) Synthesis of 3,3'-dithiodipropylisocyanate:

[0066] Dissolve 4,4'-dithiodibutyric acid hydrazide ...

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 bi-functional polyethylene glycol derivative and a preparation method thereof. The preparation method of the difunctional polyethylene glycol derivative comprises following steps: conducting esterification, hydrazinolysis and Curtius rearrangement in dibasic acid with disulfide bond at first to generate diisocyanate containing disulfide bond, then conducting a reaction of the diisocyanate and the polyethylene glycol to generate isocyanat-terminated polyethylene glycol and obtaining the bi-functional polyethylene glycol derivative through hydrolysis reaction of the resultant. In the invention, the preparation method has the advantages that raw materials can be gotten easily, reaction conditions are gentle, yield and product purity are high and the method is beneficial to mass production. Meanwhile, the bi-functional polyethylene glycol derivative is beneficial to both consequent reactions and controlled release of drugs and transfer of the drugs from endosome to cytoplasm. Application prospects of the bi-functional polyethylene glycol derivative are wide in surface finish of a nano-drug carrier, preparation of pro-drug and control of drug release speed etc.

Description

technical field [0001] The invention belongs to the technical field of biomedical materials, and in particular relates to a bifunctional polyethylene glycol derivative and a preparation method thereof. Background technique [0002] Polyethylene glycol is a synthetic, non-toxic, biocompatible polymer with good solubility in water and most organic solvents. It is a pharmaceutical polymer approved by the US FDA for internal injection. one of the things. Polyethylene glycol is the polymer with the lowest level of protein and cell adsorption known so far, which makes it have important scientific research value and practical application prospect in the field of biotechnology. The main performance is that it has great application potential in drug delivery, three-dimensional cell culture and tissue regeneration repair, and has attracted extensive attention from scholars in related fields at home and abroad. Especially in the field of drug delivery, the use of pH-neutral hydrophili...

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): C07C323/25C07C319/22A61K47/48C08G65/48
Inventor 钱军民徐明辉金欣霞柳雪峰胥伟军
Owner XI AN JIAOTONG UNIV
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