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

Polymer capable of performing addition reaction with thiol and having stable bonding hydrolysis

A hydrophilic polymer, number-average molecular weight technology, applied in the polymer field, can solve the problems of cumbersome introduction process and limited application scope, and achieve the effect of avoiding biological toxicity and hydrolysis stability.

Active Publication Date: 2012-05-16
TSINGHUA UNIV
View PDF3 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the introduction process of vinylsulfone group is cumbersome, and the production and synthesis process is easy to introduce toxic small molecules, so the current application range is still very limited

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
  • Polymer capable of performing addition reaction with thiol and having stable bonding hydrolysis
  • Polymer capable of performing addition reaction with thiol and having stable bonding hydrolysis
  • Polymer capable of performing addition reaction with thiol and having stable bonding hydrolysis

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0026] Example 1. Preparation of linear PEG that can undergo addition reaction with sulfhydryl groups and is bonded and hydrolytically stable

[0027] The compound represented by formula (II) was prepared by using PEG (number average molecular weight of about 2000, provided by Alfa-Aesar, product number B22181) with hydroxyl end group as raw material, wherein n is an integer greater than 30 and less than 60.

[0028]

[0029] Formula (II)

[0030] The specific preparation method is as follows:

[0031] Dissolve 20.0 g of hydroxyl-terminated PEG in 500 mL of dry dichloromethane, add 8.3 mL of triethylamine and 11.4 g of p-toluenesulfonyl chloride, and react at room temperature for 24 hours. Reflux for 4 hours, and then mix the obtained product with 2M ammonia in methanol and stir for 4 hours under the protection of nitrogen to obtain mercapto-terminated PEG.

[0032] Dissolve 9.0 g of ethyl hydroxymethacrylate (provided by TCI, product number H0916) in 75 mL of anhydrous e...

Embodiment 2

[0035] Example 2. Preparation of linear PEG that can undergo addition reaction with sulfhydryl groups and is stable in bond hydrolysis

[0036] The compound represented by formula (III) was prepared by using PEG with hydroxyl end group (the number average molecular weight is about 2000, provided by Alfa-Aesar, product number B22181) as raw material, wherein n is an integer greater than 30 and less than 60.

[0037]

[0038] Formula (III)

[0039] Ethyl bromomethacrylate can be obtained by the method in Example 1.

[0040] Dissolve 20.0 g of hydroxyl-terminated PEG in 300 mL of dichloromethane, add 2.4 g of sodium hydride, and stir for 1 hour. 8 mL of ethyl bromomethacrylate was added dropwise in an ice bath, and reacted at room temperature for 24 hours to obtain the product (compound represented by formula III).

[0041] The structure of the resulting compound can be obtained from figure 2 The H NMR spectrum was confirmed.

Embodiment 3

[0042] Example 3, hydrolytically stable in situ cross-linked hydrogel

[0043] The compound of formula II prepared in Example 1 and four-arm terminal mercapto PEG (number average molecular weight is about 10,000, provided by JenChem, product number 4ARM-SH-10K) were respectively dissolved in phosphate buffer at pH = 7.4 with a concentration of 0.1 mol / L The mass concentration of the two solutions is 0.1g / mL, and the two solutions are mixed at a volume ratio of 2:3, and the gel is formed within 7 hours after mixing evenly.

[0044] Or the compound of formula II prepared in Example 1 and the four-arm terminal mercapto PEG were respectively dissolved in phosphate buffer solution with a concentration of 0.1 mol / L at pH=8.0, and the mass concentration of both solutions was 0.1 g / mL. The two solutions were mixed at a volume ratio of 2:3, and gelled within 1 hour after mixing evenly.

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 polymer which can perform addition reaction with thiol and has stable hydrolysis. The polymer is formed by introducing at least one functional group shown in a formula (I) to a chain side and / or a chain end of a hydrophilic polymer, wherein X is any group or polymer chain. The polymer has the advantages that: the polymer can react with proteins or polypeptides under physiological environment without other micromolecule components, so the probably brought biotoxicity is avoided and the proteins to be modified are not influenced; and ester bonds, amido bonds, amido ester bonds and other easily hydrolytic chemical bonds are absent between the chemical bond formed after the addition reaction and a main chain, so the hydrolysis is stable.

Description

technical field [0001] The invention relates to a macromolecule capable of addition reaction with sulfhydryl groups and stable in bond hydrolysis. Background technique [0002] Protein and polypeptide drugs have become a research hotspot in recent years due to their specific effects and high efficiency. However, these drugs have problems such as poor stability, short plasma half-life and immunogenicity, which limit their application development. Since the 1970s, people began to use polymers (especially polyethylene glycol, PEG) to modify proteins and polypeptide molecules, so that the above problems were solved or alleviated. Today, this macromolecular modification technology has not only been widely used in the development of protein drugs, but also extended to various fields such as new drug carriers and controlled release preparations. In order to bind macromolecules (such as PEG) to proteins (or polypeptides), it is necessary to properly modify the macromolecules to hav...

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 Patents(China)
IPC IPC(8): C08G65/48C08J3/24C08J3/075C07K1/107
Inventor 童新明郭宝华赖菁菁黄延宾
Owner TSINGHUA UNIV
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