Preparation method of glucose-triggered active oxygen response injection type composite hydrogel

A composite hydrogel and glucose oxidase technology, applied in biochemical equipment and methods, medical preparations containing active ingredients, medical preparations with non-active ingredients, etc., can solve the problem of high-sugar environmental diseases, natural GOx Poor stability, short half-life in vivo, etc., to achieve excellent stability and mechanical properties, good biocompatibility, and simple preparation methods

Pending Publication Date: 2021-11-05
BEIJING UNIV OF CHEM TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, similar to most protein drugs, natural GOx has disadvantages such as poor stability, short half-life in vivo, and systemic toxicity, making it difficult to be directly used in the treatment of diseases in high-glucose environments.

Method used

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  • Preparation method of glucose-triggered active oxygen response injection type composite hydrogel
  • Preparation method of glucose-triggered active oxygen response injection type composite hydrogel
  • Preparation method of glucose-triggered active oxygen response injection type composite hydrogel

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preparation example Construction

[0054] figure 1 A schematic flow chart showing a method for preparing a glucose-triggered reactive oxygen species-responsive injectable composite hydrogel according to an embodiment of the present invention. Such as figure 1 As shown, the preparation method of the active oxygen response injectable composite hydrogel comprises:

[0055] Step S100, preparing a hyaluronic acid-aminophenylboronic acid derivative HA-g-PBA with phenylboronic acid in the main chain and an acrylic acid-modified glucose oxidase derivative GOx-AC;

[0056] Step S200, using the Michael addition reaction between the thiol group of mercaptophenylboronic acid and the acrylate group of GOx-AC to prepare the glucose oxidase derivative GOx-g-PBA with phenylboronic acid;

[0057] In step S300, the hydroxyl group of GOx-g-PBA and the hydroxyl group of polyvinyl alcohol form borate dynamic covalent bonds to prepare polyvinyl alcohol derivative PVA-g-GOx modified with glucose oxidase;

[0058] Step S400, mixing...

Embodiment 1

[0090] A method for preparing a glucose-triggered active oxygen response injectable composite hydrogel, comprising the steps of:

[0091] 1) Preparation of hyaluronic acid-aminophenylboronic acid derivative (HA-g-PBA)

[0092] Dissolve 2g HA (molecular weight 40KDa) in 800mL of ultrapure water, then add 690mg of 4-aminophenylboronic acid dissolved in 100mL of DMSO solution, then add 1530mg of 1-ethyl-3-(3-dimethylaminopropyl)carbon Diimide hydrochloride, and adjust the pH of the solution to 4.5-5.0 by hydrochloric acid, then add 920mg N-hydroxysuccinimide, and react for 6 hours; the product HA-g-PBA solution is purified by dialysis (using a molecular weight cut-off of 8- 10KDa dialysis bag) and freeze-dried for storage.

[0093] 2) Preparation of polyvinyl alcohol derivatives modified with glucose oxidase

[0094] Dissolve 50 mg of glucose oxidase in 5 mL of buffer solution (PBS, pH=7.4-8.0, 150 mM), and another 10 μL of N-acryloyloxysuccinimide 10% (w / v) DMSO solution was a...

Embodiment 2

[0100] A preparation method of glucose-triggered reactive oxygen species responsive injectable composite hydrogel, the preparation method comprising the following steps:

[0101] 1) Preparation of hyaluronic acid-aminophenylboronic acid derivative (HA-g-PBA)

[0102] Dissolve 2g HA (molecular weight 20KDa) in 800mL of ultrapure water, then add 1380mg of 4-aminophenylboronic acid dissolved in 100mL of DMSO solution, then add 3060mg of 1-ethyl-3-(3-dimethylaminopropyl)carbon Diimide hydrochloride, and adjust the pH of the solution to 4.5-5.0 by hydrochloric acid, then add 1920mg N-hydroxysuccinimide, and react for 6 hours; the product HA-APBA solution is purified by dialysis (molecular weight cut-off 8-10KDa dialysis bag ) and then freeze-dried.

[0103] 2) Preparation of polyvinyl alcohol derivatives modified with glucose oxidase

[0104] Dissolve 50 mg of glucose oxidase in 5 mL of buffer solution (PBS, pH=7.4-8.0, 150 mM), and another 10 μL of N-acryloyloxysuccinimide 10% (...

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Abstract

The invention provides a preparation method of glucose-triggered active oxygen response injection type composite hydrogel. The preparation method comprises the following steps of preparing a hyaluronic acid-aminophenylboronic acid derivative HA-g-PBA of which the main chain has phenylboronic acid and an acrylic group modified glucose oxidase derivative GOx-AC; carrying out Michael addition reaction on sulfydryl of sulfydryl phenylboronic acid and an acrylate group of GOx-AC to prepare a derivative GOx-g-PBA with phenylboronic acid glucose oxidase; forming a borate dynamic covalent bond through a hydroxyl group of GOx-g-PBA and a hydroxyl group of polyvinyl alcohol, so as to prepare a polyvinyl alcohol derivative PVA-g-GOx modified with glucose oxidase; and mixing HA-g-PBA and PVA-g-GOx according to a preset proportion, and then forming boric acid ester dynamic covalent bonds to prepare the glucose-triggered active oxygen response injection type composite hydrogel. The preparation method is simple and has a good application prospect, and the degradation period can be regulated and controlled through dual response of glucose and active oxygen.

Description

technical field [0001] The invention relates to a preparation method of an injectable hydrogel applied in the field of biomedicine, in particular to a preparation method of a glucose-triggered active oxygen response injectable composite hydrogel. Background technique [0002] Hydrogel is a high molecular weight polymer with a three-dimensional network structure, and its cross-linked network structure can prevent penetration. These properties make it a good drug carrier and can be applied to surgical implantation, local needle injection and intravenous injection. Full body delivery. However, most of the hydrogels currently researched and applied are through physical cross-linking, using changes in the internal environment of body tissues (temperature, pH value, and ionic strength, etc.) to trigger the formation of hydrogel networks. Thermosensitive alginic acid-g-poly(N-isopropylacrylamide, grafted poly(N-isopropylacrylamide) and poly(methacrylic acid) onto the cyclic oligos...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/44A61K47/61A61K47/58A61K9/06A61P3/10C08J3/075C08J3/24C08L5/08C08L29/04
CPCA61K38/443C12Y101/03004A61K47/61A61K47/58A61K9/06A61K9/0019A61P3/10C08J3/075C08J3/246C08J2305/08C08J2329/04
Inventor 张建军赵伟周雨晨刘捷
Owner BEIJING UNIV OF CHEM TECH
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