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Biocompatible quick-gelatinizing hydrogels and method for preparing spray thereof

A biocompatible and hydrogel technology, which is applied in the preparation of biocompatible fast-gelling hydrogels and the preparation of biocompatible fast-gelling hydrogel sprays, can solve the problem of expensive and easy to lose activity. , inconvenient to use, etc.

Active Publication Date: 2009-01-07
BIOREGEN BIOMEDICAL (CHANGZHOU) CO LTD
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

The second is that the multi-arm polyethylene glycol succinimide activated derivative solution and the multi-arm polyethylene glycol mercapto derivative solution adopted by Wallace etc. are very unstable, both need fresh configuration, and the former solution needs to be in Use it up within one hour, the latter will easily lose its activity when exposed to air, which is very inconvenient to use
The third is that multi-arm polyethylene glycol mercapto derivatives and multi-arm polyethylene glycol succinimide activated derivatives are very expensive, and only the concentration of these two compounds is as high as 10% w / v or more (usually 20 %w / v) to achieve rapid gelation, the cost is very high

Method used

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  • Biocompatible quick-gelatinizing hydrogels and method for preparing spray thereof
  • Biocompatible quick-gelatinizing hydrogels and method for preparing spray thereof
  • Biocompatible quick-gelatinizing hydrogels and method for preparing spray thereof

Examples

Experimental program
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Effect test

Embodiment 1

[0112] Embodiment 1 Preparation of thiol-modified hyaluronic acid (HA-DTPH)

[0113] Prepared by the method reported by Shu et al. (Shu et al., Biomacromolecules, 3, 1304, 2002).

[0114] Dissolve 20 grams of sodium hyaluronate (molecular weight about 1.5 million) in 2 liters of distilled water, add concentrated hydrochloric acid to adjust the pH value of the solution to about 0.5, and then degrade it in a shaker at 37 degrees Celsius and 150 rpm for 24 hours. Dialysis, purification, freeze-drying to obtain low molecular weight hyaluronic acid (weight average molecular weight 246,000, number average molecular weight 120,000).

[0115] 20 grams of the above low molecular weight hyaluronic acid was dissolved in 2 liters of distilled water. Add 23.8 g of dithiodimalonohydrazide (prepared according to the method disclosed in Biomacromolecules, 3, 1304, 2002 by Shu et al.) to the above solution, and stir to dissolve. Then the pH value of the solution was adjusted to 4.75 with 0.1...

Embodiment 2

[0118] Example 2 Preparation of mercapto-reactive biocompatible cross-linking agent

[0119] Polyethylene glycol diacrylate, polyethylene glycol di(meth)acrylate, polyethylene glycol diacrylamide and polyethylene glycol di(meth)acrylamide are prepared by corresponding polyethylene glycol (molecular weight 3,400 or 10,000, Sigma-Aldrich, U.S.) and polyethylene glycol diamine (molecular weight 3400, Nektar Therapeutics, U.S.) preparation, multiarm (4 arms and 8 arms) polyethylene glycol diacrylate and polyethylene glycol Di(meth)acrylates were prepared from the corresponding multi-armed polyethylene glycols (molecular weight 10,000). The general process of its preparation is that polyethylene glycol or polyethylene glycol diamine reacts with acryloyl chloride or methacryloyl chloride under the action of triethylamine, and the product can be obtained after purification. For the detailed process, see Shu et al., Biomaterials, 25, 1339, 2004.

[0120] Replace the corresponding ac...

Embodiment 3

[0121] Example 3 Preparation of Biocompatible Rapid Gelation Hydrogel

[0122] The HA-DTPH solution (2.0% w / v, pH 5.0) prepared in Example 1 was thawed at room temperature for use. Polyethylene glycol diacrylate (molecular weight 3400, Nektar Therapeutics, USA) was dissolved in 0.3 mol / L sodium phosphate / sodium carbonate buffer to obtain a 2.0% w / v solution (pH 9.6), which was sterilized by filtration for use. Under electromagnetic stirring, the above-mentioned solution (5 milliliters) was quickly added into another solution (5 milliliters), and the stirring was continued for 3 seconds, then the stirring was stopped. The pH value of the reactive mixture was about 9.4, and the mixed solution lost its The fluidity forms a gel.

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Abstract

The invention discloses a preparation method for biocompatible rapid gelating hydrogel. The hydrogel is formed by that a plurality of active compound components mix and undergo chemical cross linking reaction to rapidly chemically cross link under the specified conditions. The preparation method comprises the following steps: (1) a solution (component A) containing biocompatible macromolecular mercapto-derivatives and biocompatible mercapto reactive crosslinking agents (component B) mutually mix to form reactive mixture with specified cross linking conditions; (2) the reactive mixture forms the hydrogel. The invention also discloses a preparation method for novel rapid gelating hydrogel spray and an application in the medical field. The invention has the advantages of good biocompatibility, no by-products, good stability, convenient use, small amount of raw materials, many medical application, etc.

Description

technical field [0001] The invention relates to a preparation method of a hydrogel, in particular to a preparation method of a biocompatible rapid gelling hydrogel. The invention also relates to a preparation method of the biocompatible rapid gelling hydrogel spray. Background technique [0002] Hydrogels, especially those prepared from intercellular matrix, have been widely used in the field of biomedicine. Compared with hydrogels prepared from synthetic materials, hydrogels prepared from intercellular matrix have many advantages: such as simulating the natural environment in organisms, high water content, good permeability, better biological Compatibility, and adjustable enzyme degradation performance, etc. (Silva et al., Curr Top Dev Biol, 64, 181, 2004; Drury et al., Biomaterials, 24, 4337, 2003). More importantly, the intercellular matrix can have a bioinductive effect, which can direct and induce tissue-specific repair. For example, sodium hyaluronate is a natural i...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C08J3/24C08J3/075C08L5/08C08L5/10C08L5/04C08L5/06C08L1/26C08K5/36A61K31/715A61K9/00
CPCC08G75/04A61L27/52A61P17/02C08G75/045C08G75/12
Inventor 舒晓正
Owner BIOREGEN BIOMEDICAL (CHANGZHOU) CO LTD
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