PEG (Polyethylene Glycol), mPEG (Methoxy Polyethylene Glycol) chemical modifier and method thereof for preparing water-soluble resveratrol prodrug

A chemical modifier, the technology of resveratrol, applied in the direction of pharmaceutical formulations, antipyretics, anti-inflammatory agents, etc., can solve the problems of unstable properties of resveratrol, reduced biological activity, limited use range, etc., to improve Water solubility and stability, enhanced biological activity, wide range of application effects

Inactive Publication Date: 2010-10-27
HEBEI UNIVERSITY OF SCIENCE AND TECHNOLOGY
View PDF3 Cites 15 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, because resveratrol contains a stilbene core structure, its water solubility is very poor, it is difficult to dissolve in water, and it is inconvenient to use, which limits its scope of use.
In addition, resveratrol is unstable in nature, easy to oxidize, and easily transf

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
  • PEG (Polyethylene Glycol), mPEG (Methoxy Polyethylene Glycol) chemical modifier and method thereof for preparing water-soluble resveratrol prodrug
  • PEG (Polyethylene Glycol), mPEG (Methoxy Polyethylene Glycol) chemical modifier and method thereof for preparing water-soluble resveratrol prodrug
  • PEG (Polyethylene Glycol), mPEG (Methoxy Polyethylene Glycol) chemical modifier and method thereof for preparing water-soluble resveratrol prodrug

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0043] Example 1 Prepare PEG chemical modifier with PEG6000, and further use the modifier to modify resveratrol to prepare water-soluble resveratrol prodrug

[0044] This embodiment includes the following steps:

[0045] (1) Preparation of PEG6000 carboxylic acid derivatives

[0046] The reaction formula is as follows:

[0047]

[0048] Specific operation process: Take 30g (0.005mol) of dry PEG (polyethylene glycol), dissolve it in 200mL chloroform solution, add 1.5g (0.015mol) of succinic anhydride, stir evenly, add 2ml of pyridine, heat to reflux; react for 48h, After the reaction was completed, the solvent was evaporated, and the residue was washed with 100 mL saturated NaHCO 3The solution was dissolved, extracted 3 times with 30 mL of ethyl acetate, and the resulting aqueous phase was adjusted to pH 2-3 with dilute hydrochloric acid; then extracted with dichloromethane, the organic phases were combined, washed with water to neutralize, dried, concentrated under reduce...

Embodiment 2

[0062] Example 2 Prepare PEG chemical modifier with PEG5000, and further use the modifier to modify resveratrol to prepare water-soluble resveratrol prodrug

[0063] (1) Preparation of PEG5000 carboxylic acid derivatives

[0064] The reaction formula is as follows:

[0065]

[0066] Specific operation: Take 30g (0.006mol) of PEG5000, dissolve in 150mL toluene, evaporate 30mL of toluene, cool to room temperature, add NaH 0.43g (0.018mol) solution under ice bath, stir for 15min, add dropwise 11g of ethyl bromoacetate (0.066mol), reflux for 24 hours, filter, the filtrate is evaporated under reduced pressure to remove toluene, the residue is dissolved in dichloromethane, slowly poured into diethyl ether under stirring, a white solid is precipitated, filtered by suction, and dried in vacuo to obtain PEG or mPEG carboxylic acid The ester was hydrolyzed in 120 mL of NaOH solution with a concentration of 1 mol / L, and reacted at room temperature for 4 h under stirring. Under ice-w...

Embodiment 3

[0080] Example 3 Prepare a PEG chemical modifier with mPEG4000, and further use the modifier to modify resveratrol to prepare a water-soluble resveratrol prodrug

[0081] (1) Preparation of mPEG4000 carboxylic acid derivatives

[0082] The reaction formula is as follows:

[0083]

[0084] Specific operation: Take 30g (0.0075mol) of mPEG4000, dissolve in 150mL toluene, evaporate 30mL of toluene, cool to room temperature, add 0.27g (0.011mol) solution under ice bath, stir for 20min, add dropwise isopropyl bromoacetate 8.5 g (0.045mol), reflux reaction for 20h, filter, the filtrate is evaporated under reduced pressure to remove toluene, the residue is dissolved in dichloromethane, slowly poured into diethyl ether under stirring, a white solid is precipitated, filtered by suction, and dried in vacuo to obtain PEG or mPEG carboxyl The acid ester was hydrolyzed in 120 mL of NaOH solution with a concentration of 1 mol / L, and reacted at room temperature for 3 h under stirring. Un...

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 PEG (Polyethylene Glycol)/mPEG (Methoxy Polyethylene Glycol) chemical modifier and a method thereof for preparing a water-soluble resveratrol prodrug. In the PEG/mPEG chemical modifier, PEG or mPEG is used as a vector, and the chemical modifier is prepared through reacting succinic anhydride, bromoacetate or isobutyl bromoacetate with amino acid. The preparation conditions and steps of the chemical modifier are simple. The chemical modifier is used for modifying the resveratrol to prepare the resveratrol prodrug, can change the water solubility and the stability of the resveratrol, is convenient to use and improves the bioactivity. When the prodrug is decomposed in vivo, amino acid required by the human body is also released while the resveratrol is released, thus the application scope of the prodrug is wider than that of the resveratrol.

Description

technical field [0001] The invention belongs to the field of compound and pharmacy, and specifically relates to a PEG and mPEG chemical modifier and a preparation method, and a method for preparing water-soluble resveratrol prodrug by using the modifier as a modifier to modify resveratrol. Background technique [0002] The chemical name of resveratrol (resveratrol, RES) is 3,4′,5-trihydroxystilbene, which is the most common stilbene compound, widely present in many plants such as grapes, knotweed and hellebore, It has various pharmacological activities such as anti-tumor, anti-bacterial, anti-inflammatory, anti-allergic, hypolipidemic and anti-oxidant. However, because resveratrol contains a stilbene core structure, its water solubility is very poor, it is difficult to dissolve in water, and it is inconvenient to use, which limits its application range. In addition, resveratrol is unstable in nature, easy to oxidize, and easily transforms into a cis-configuration under ultr...

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): C08G65/48A61K47/48A61P35/00A61P31/00A61P29/00A61P37/08A61P3/06A61P39/06A61K47/60
Inventor 张越韩玉翠卜辉娟郑和堂
Owner HEBEI UNIVERSITY OF SCIENCE AND TECHNOLOGY
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