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Preparation method and application of bis-azide-substituted polytetraethylene glycol

A polytetraethylene glycol and diazide technology is applied in the fields of anti-inflammatory, diazide-substituted polytetraethylene glycol compound and its preparation, promoting wound healing, and sterilization, so as to promote expression, improve healing effect, The effect of promoting proliferation and migration

Active Publication Date: 2018-03-20
NANKAI UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] The role of azides in promoting wound healing has never been reported before

Method used

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  • Preparation method and application of bis-azide-substituted polytetraethylene glycol
  • Preparation method and application of bis-azide-substituted polytetraethylene glycol
  • Preparation method and application of bis-azide-substituted polytetraethylene glycol

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0047] Example 1 Synthesis process of diazide substituted polytetraethylene glycol and nuclear magnetic detection results

[0048] 1. Synthesis of diazide-substituted polytetraethylene glycol

[0049] 1.1 Synthetic reaction route:

[0050] The reaction route is as follows:

[0051]

[0052] The preparation method is: take 40mL of tetrahydrofuran in N 2 10.156 g of polyethylene tetraethylene glycol was added under protection, and then 9 mL of methanesulfonyl chloride was added with a syringe and stirred. Under ice bath conditions, 16.2 mL of triethylamine and 10 mL of tetrahydrofuran were mixed and added dropwise to the flask, followed by a yellow-white precipitate. After 1 hour the ice bath was removed and the mixture was stirred for 3.5 hours. Withdraw dropwise and N 2 Protect the device, add 24.4mL of water to dissolve, and form two liquid phases. After cooling on ice bath, add NaHCO 3 Adjust pH≥8, then add 6.976g NaN 3 , refluxed for 24 hours. Finally, the desired...

experiment example 1

[0055] Experimental example 1 Establishment of mouse wound model and pharmacodynamics test of diazide-substituted PEG

[0056] 1. Establishment of mouse wound model and drug treatment

[0057] 1.1 Establishment of mouse wound model

[0058] Twelve mice were randomly divided into 3 cages with 4 mice per cage, numbered 1-3. After each mouse was anesthetized with 10% chloral hydrate at a dose of 0.3 mL / 100 g, the hair on the back of the mouse was removed with a shaver, and the back skin was wiped with 70% ethanol to create two wounds, respectively, and hemostatic cotton was used to stop bleeding. Salt water wipe, that is, the modeling is successful.

[0059] 1.2 Administration of wound healing mice

[0060] After modeling, mice were dosed. The administration method was external use, and 1% gelatin and diazide-substituted polytetraethylene glycol gelatin solution were applied to the two wounds of each mouse. And the wounds of the mice were observed and photographed every day....

experiment example 2

[0068] Experimental Example 2 The effect of diazide-substituted PEG on the proliferation and migration of mouse fibroblasts (NIH-3T3) and human immortalized epidermal cells (HaCaT)

[0069] The effect of diazide-substituted polyethylene tetraethylene glycol on the growth of mouse fibroblasts (NIH-3T3) and human immortalized epidermal cells (HaCaT) by MTT colorimetry

[0070] Method steps:

[0071] (1) Cell recovery and culture

[0072] The cryopreserved NIH-3T3 cells and HaCaT cells were taken out from liquid nitrogen, thawed into a petri dish, and placed at 37°C, 5% CO. 2 , cultured under conditions of saturated humidity.

[0073] (2) MTT assay to determine the effect of drugs on cell proliferation

[0074] Adherent cells in logarithmic growth phase were trypsinized and seeded on 96-well culture plates at 5000 cells per well. Placed in a 37°C, 5% carbon dioxide incubator overnight for 24 hours to allow cells to adhere. After 24 hours, the culture medium was discarded, an...

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Abstract

The invention provides diazido-substituted poly(tetraethylene glycol), and the structural formula is as follow (please see the formula in the description).The synthesized diazido-substituted poly(tetraethylene glycol) can promote proliferation and migration of fibroblasts and epithelial cells, promote expression of collagen I protein in the cells, stimulate cell factors including NF-kappaB, STAT3, AP1 and Myc which are included in the cells and related to an inflammatory reaction to comprehensively play a role in wound healing promotion and enable the cell factors to achieve the significant treatment effect at the extremely low dosage.Therefore, the diazido-substituted poly(tetraethylene glycol) is likely to change the market pattern of existing wound healing promotion drugs and becomes a clinical drug which can be used for a long term, effectively promote wound healing and improve the healing effect.

Description

technical field [0001] The invention relates to the field of medicinal chemistry, in particular to a diazide-substituted polytetraethylene glycol compound and a preparation method thereof, as well as its functions in promoting wound healing, anti-inflammatory and sterilization. Background technique [0002] The skin is the largest organ of the human body and plays an important role in protecting the human body. The healing process of skin tissue after injury is a complex process in which many factors are involved. Collagen, as an important part of extracellular matrix, constitutes the main part of new skin tissue. Matrix metalloproteinases (MMPs) can cleave extracellular matrix components as well as other proteases, growth factors, etc. Transforming growth factor (TGF-β) promotes collagen deposition, epidermal cell migration, and affects the shaping of extracellular matrix. NF-κB, AP1, STAT3, Myc, etc., as cellular pathway factors related to inflammatory response, play an...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07C247/04A61P17/02A61P29/00A61P31/04A61P31/10
CPCC07C247/04Y02A50/30
Inventor 杨诚孙涛周红刚孙波刘慧娟刘艳荣陈双李阳刘学强周磊于恒恒秦源孟晶仲威龙
Owner NANKAI UNIV
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