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Preparation method of multiple cross-linked polysaccharide injectable hydrogel

A multi-crosslinking, hydrogel technology, applied in pharmaceutical formulations, medical preparations with non-active ingredients, pharmaceutical sciences, etc., can solve problems such as poor solubility, achieve enhanced stability and mechanical strength, good application prospects, improve The effect of biocompatibility

Inactive Publication Date: 2015-04-01
SHANGHAI UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Poor solubility has become the main factor limiting the application of chitosan

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0024] In this example, a method for preparing a multiple cross-linked polysaccharide injectable hydrogel, the preparation process is as follows:

[0025] Weigh 0.3g chitosan, dissolve it in 100ml water, add 0.264mL lactic acid, after stirring and dissolving completely, add N - Hydroxysuccinimide 0.424g, adjust the pH to 4.8, 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride 1.411g, react for 36h, adjust the pH to 7.0. The product was dialyzed and freeze-dried; Weighed 2.5g of alginic acid and added it to 50mL of water, stirred and dissolved in a water bath, after it was completely dissolved, added 1.08g of sodium periodate, reacted for 3h under light-shielded conditions, and added 600μL of ethylene glycol to stop reaction. The product was dialyzed and lyophilized. The modified chitosan and alginic acid were respectively prepared into 0.5wt% aqueous solution, mixed in equal volumes, and a hydrogel was obtained after 156s with a storage modulus of 132 Pa.

[0026] I...

Embodiment 2

[0028] This embodiment is basically the same as Embodiment 1, especially in that:

[0029] In this example, weigh 0.3g of chitosan, dissolve it in 100mL of water, add 0.132mL of glycolic acid, gradually add a certain amount of hydrochloric acid until the chitosan is completely dissolved, then add N-Hydroxysuccinimide 0.424g, adjust the pH to 4.7, 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride 1.411g, react for 48h, adjust the pH to 7.0. The product was dialyzed and freeze-dried; Weighed 2.5g of sodium hyaluronate and added it to 50mL of water, stirred and dissolved in a water bath. Alcohol terminates the reaction. The product was dialyzed and lyophilized. The modified chitosan and sodium hyaluronate were prepared into 1wt% aqueous solution, mixed in equal volumes, and a hydrogel was obtained after 70 s with a storage modulus of 257 pa.

Embodiment 3

[0031] This embodiment is basically the same as the previous embodiment, and the special features are:

[0032] In this example, weigh 0.3g of chitosan, dissolve it in 100mL of water, add 0.132mL of lactic acid, gradually add a certain amount of hydrochloric acid until the chitosan is completely dissolved, then add N -Hydroxysuccinimide 0.636g, adjust the pH to 4.7, 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride 2.116g, react for 48h, adjust the pH to 7.0. The product was dialyzed and freeze-dried; weighed 2.5g of carboxymethyl chitosan and added it to 50mL of water, stirred and dissolved in a water bath. Ethylene glycol terminates the reaction. The product was filtered, settled with acetone, redissolved, dialyzed and freeze-dried. The two kinds of modified chitosan were made into 1wt% aqueous solution, mixed in equal volumes, and hydrogel was obtained after 113s, with a storage modulus of 195 pa.

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Abstract

The invention discloses a preparation method of multiple cross-linked polysaccharide injectable hydrogel. Modified water-soluble chitosan with carboxyl or hydroxyl groups as a first component and a hydroformylation-modified polysaccharide polymer or polysaccharide polymer mixer as a second component produce electrostatic action with each other and undergo a Schiff-base reaction to produce the hydrogel with a multiple cross-linked net structure. The multiple cross-linked polysaccharide injectable hydrogel has gelling time of 5-200s and has good mechanical properties. Through change of a chitosan and polysaccharide modification rate, a mole ratio of two components and solid content of hydrogel, gelling time, mechanical strength, microscopic morphology and water content are adjusted and controlled. The gel network contains a large amount of amino, carboxyl and aldehyde groups as active groups, the active groups can be bonded to drugs and proteins by covalent bonds, the multiple cross-linked polysaccharide injectable hydrogel as a novel medical material with excellent biocompatibility has a good application prospect in the fields of regeneration medical science, tissue engineering and drug controlled release.

Description

technical field [0001] The invention relates to a preparation method of hydrogel, in particular to a preparation method of injectable hydrogel, which is applied in the technical fields of regenerative medicine, tissue engineering, drug controlled release and the like. Background technique [0002] Hydrogel is a hydrophilic polymer network, which can absorb a large amount of water, but will not dissolve in water due to the physical cross-linking and chemical cross-linking between polymer chains, and can only swell and maintain a certain shape. Hydrogels have good biocompatibility and water permeability, and hydrogel materials with different microstructures and properties can be obtained through artificial synthesis. These properties make hydrogels widely used in the field of biomedicine. In the field of regenerative medicine, research into injectable hydrogels has been particularly compelling. Injectable hydrogels can be used for controlled release of bioactive molecules, em...

Claims

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Application Information

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IPC IPC(8): C08J3/24C08J3/075C08L5/08C08L5/04C08L1/26C08B37/08C08B37/04C08B15/10A61L27/20A61L27/52A61K47/48
Inventor 颜世峰王滔滔王耀伟许娇娇方圆孙园园宋丽尹静波
Owner SHANGHAI UNIV
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