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Injectable hydrogel type biological adhesive as well as preparation and application thereof

A technology of hydrogel, injection, applied in the direction of application, surgical adhesive, surgery, etc.

Active Publication Date: 2022-04-12
EAST CHINA UNIV OF SCI & TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the relatively constant rate of gelation makes it technically challenging to use such hydrogels for minimally invasive delivery

Method used

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  • Injectable hydrogel type biological adhesive as well as preparation and application thereof
  • Injectable hydrogel type biological adhesive as well as preparation and application thereof
  • Injectable hydrogel type biological adhesive as well as preparation and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0161] Embodiment 1: Research on the mechanism of gelation time

[0162] 1. Hydrogel Preparation

[0163] Before preparing the hydrogel, the LZM was first purified by dialysis-lyophilization (3d) to remove the acidic substances in the protein. Use normal saline (0.9%, w / v) to dissolve Borax to prepare different Borax content saline solutions, use it to dissolve LZM or other proteins (15%, w / v) as gel-forming precursor solution A, and use normal saline to dissolve 4arm PEG- SC (15%, w / v) was used as gel-forming precursor solution B. Put the equal volumes of the gel-forming precursors A and B into the double-barrel mixer syringe), install the injection needle or sprayer at the nozzle of the double-barrel syringe, and quickly inject them into different molds to form PEG-LZM / Borax or other PEG -Protein / Borax hydrogel.

[0164] 2. Determination of gelation time

[0165] In this experiment, the gelation time was determined by the vial tilt method. At room temperature (25°C), pr...

Embodiment 2

[0178] Embodiment 2: Mechanism versatility evaluation

[0179] Use normal saline or normal saline containing 20mg / mL Borax to dissolve a series of proteins such as LZM, BSA, OVA as gel-forming precursor A (15%, w / v), and dissolve 4-arm-PEG-NHS with normal saline as Gelling precursor solution B (15%, w / v); after mixing and injecting the gelling precursors, observe the gelation situation.

[0180] Such as figure 2 As indicated, the LZM in the PEG-LZM hydrogel was replaced with bovine serum albumin (BSA), human hemoglobin (HGB), chicken ovalbumin (OVA), etc., and their interactions with 4-arm-PEG-NHS were determined reaction speed. It was found that when Borax was not added, all proteins had poor reactivity with 4-arm-PEG-NHS, and no gelation occurred within 10 min. However, after adding Borax, the gelation speed of all systems was significantly accelerated, and various hydrogels could rapidly form hydrogels within 30 seconds after injection. Therefore, the addition of Borax...

Embodiment 3

[0181] Embodiment 3: Determination of pH and gelation time in gel-forming precursor solution A

[0182] Refer to the method in Example 1 to measure the pH and gelation time in gel-forming precursor solution A.

[0183] Firstly, the content of LZM is fixed, and the pH value of gel-forming precursor solution A with different contents of Borax is measured, and the results are as follows image 3As shown in (a), when the Borax concentration is above 8 mg / mL, the pH value in the solution decreases slowly with the decrease of the Borax concentration, indicating that Borax can provide sufficient buffer capacity to maintain the pH value of gel-forming precursor solution A at a high level The basic level of the LZM greatly enhances the nucleophilicity in the solution. And when the concentration of Borax decreased below 8mg / mL, the pH value of the solution decreased rapidly with the decrease of Borax concentration. This shows that the H produced in the gel-forming precursor solution A...

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Abstract

The invention relates to an injectable hydrogel type biological adhesive as well as preparation and application thereof. Specifically, the invention provides a hydrogel material. The hydrogel is formed by mixing a gel-forming precursor solution A and a gel-forming precursor solution B, wherein the gel-forming precursor solution A is formed by dissolving water-soluble polymers or macromolecules with more than two amino functionalities in a normal saline solution containing strong alkali and weak acid salt, and the gel-forming precursor solution B is formed by dissolving polyethylene glycol of which the tail end is modified with active ester in a normal saline solution. By adjusting the pH value in the precursor solution, the hydrogel after injection can have different gelation time from several seconds to several minutes, so that the hydrogel can be applied to multiple clinical fields such as rapid hemostasis, drug sustained release, tissue adhesion, minimally invasive delivery treatment to deep wounds in vivo and the like.

Description

technical field [0001] The invention belongs to the field of biotechnology. Specifically, the invention relates to a method for regulating gelation time based on amidation reaction, and the prepared different injectable hydrogels are applied in different medical clinical fields. Background technique [0002] Hydrogel is a polymer with a hydrophilic three-dimensional network structure, similar to the human extracellular matrix (ECM); in water it can absorb a large amount of water to swell and maintain its shape without being dissolved, so the Such materials have a wide range of applications in the clinical field. In recent years, injectable hydrogels have become a new round of research hotspots in the field of hydrogels. Injectable hydrogel refers to the formation of gel in situ after the hydrogel raw material in fluid form is simultaneously injected into the body through a syringe. "Injection in liquid state, solidification in situ" breaks through the limitation of traditi...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61L24/00A61L24/06A61L24/08A61L24/10A61L24/02C08J3/075C08L71/02
Inventor 不公告发明人
Owner EAST CHINA UNIV OF SCI & TECH