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Injectable natural hydrogel system with temperature sensitive feature and high tissue adhesive force and preparation method thereof

A natural water, temperature-sensitive technology, applied in the field of medical biomaterials, can solve the problems of low catechol grafting rate, unfavorable scale-up production, slow reaction speed, etc., and achieve good biocompatibility and degradability, high tissue quality Adhesion, not easy to shift effect

Inactive Publication Date: 2018-06-15
SHANGHAI QISHENG BIOLOGICAL PREPARATION CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, in this type of reaction, the amino group of the catechol group is used as the reactive site, and the generated amide bond changes the chemical properties of the polyamine itself. The carboxyl activator carbodiimide (EDC) and N-hydroxyl Succinimide (NHS) has high requirements on pH, requires continuous process monitoring, slow reaction speed, is not conducive to scale-up production, and the grafting rate of catechol is low

Method used

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  • Injectable natural hydrogel system with temperature sensitive feature and high tissue adhesive force and preparation method thereof
  • Injectable natural hydrogel system with temperature sensitive feature and high tissue adhesive force and preparation method thereof
  • Injectable natural hydrogel system with temperature sensitive feature and high tissue adhesive force and preparation method thereof

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Experimental program
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Effect test

Embodiment 1

[0023] 0.5 g of hydroxybutyl chitosan (molecular weight 600,000 DA) was dissolved in 50 mL of deionized water. Dissolve 0.5g of 3,4-dihydroxybenzaldehyde in 1mL of ethanol, add it into the hydroxybutyl chitosan solution while stirring after the dissolution is complete, and place it at room temperature for 16 hours after stirring evenly. Add 0.06 g of sodium borohydride after the reaction, stir rapidly, add acetic acid to quench excess sodium borohydride, dialyze with deionized water with pH=5.0 for 3 days (molecular weight cut-off 10,000), ultrafilter to a concentration of 0.8%, and obtain a sample A, for use.

[0024] Add 20uL of 100ppm ferric chloride solution into 0.5g of sample A, mix quickly, and obtain a gel with high adhesion at room temperature.

Embodiment 2

[0026] 0.25 g of hydroxybutyl chitosan (molecular weight 600,000 DA) was dissolved in 50 mL of deionized water. Dissolve 0.1g of 3,4-dihydroxybenzaldehyde in 1mL of ethanol, add it into the hydroxybutyl chitosan solution while stirring after the dissolution is complete, and place it at room temperature for 6 hours after stirring evenly. Add 0.03g of sodium borohydride after the reaction, stir rapidly, add acetic acid to quench excess sodium borohydride, dialyze with deionized water with pH=6 for 3 days (molecular weight cut-off 10000), ultrafilter to a concentration of 1%, and obtain a sample A, for use.

[0027] Add 50uL of 100ppm ferric chloride solution into 0.5g of sample A, mix quickly, and obtain a gel with high adhesion at room temperature.

Embodiment 3

[0029] 0.25 g of hydroxybutyl chitosan (molecular weight 600,000 DA) was dissolved in 50 mL of deionized water. Dissolve 0.05g of 3,4-dihydroxybenzaldehyde in 1mL of ethanol. After the dissolution is complete, add it into the hydroxybutyl chitosan solution while stirring. After stirring evenly, place it at room temperature for 4 hours. After the reaction, add 0.015g of sodium borohydride, stir rapidly, add acetic acid to quench excess sodium borohydride, dialyze with deionized water of pH=6.5 for 3 days (molecular weight cut-off 10000), and ultrafilter to a concentration of 2%, to obtain a sample A, for use.

[0030] Add 100uL ferric chloride solution containing 100ppm to 0.5g sample A, mix quickly, and get a gel with high adhesion at room temperature.

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PUM

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Abstract

The invention relates to an injectable natural hydrogel system with a temperature sensitive feature and high tissue adhesive force. The system is prepared through Schiff base reactions between micromolecular compounds containing catechol groups and a -NH2 containing temperature sensitive natural polymer material. The system has the advantages of quick temperature responding speed, good biocompatibility, good degradation property, high gel mechanical strength, and high tissue adhesive force, can be firmly adhered on needed parts in a wet environment, and is difficult to shift. At the same time,the preparation technology (Schiff base reactions) is simple, the reaction efficiency is high, and the reaction conditions are mild. During the preparation process, no any chemical crosslinking agent, activator, or photo-sensitizer is introduced into the production system, the production purification technology is simple, the maneuverability in the production process is improved for enterprises,and the preparation method is suitable for industrialization and amplified production.

Description

technical field [0001] The invention relates to the technical field of medical biomaterials, in particular to an injectable natural hydrogel and a preparation method thereof, which can be applied to surgical operations such as tissue adhesion and anti-adhesion, as well as tissue repair and drug release systems. Background technique [0002] Hydrogel has a three-dimensional network structure similar to extracellular matrix, which is beneficial to the growth of cells and the exchange of metabolic substances, so it has a wide range of applications in biomedical fields such as tissue repair and drug release. In recent years, injectable hydrogels have attracted the attention of researchers because of their unique advantages. Injectable hydrogel is to inject a biological material with certain fluidity into the desired site, and then quickly realize the sol-gel transition in the in vivo environment, adhere to the site and play a specific role. Therefore, injectable hydrogels are e...

Claims

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Application Information

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IPC IPC(8): A61L24/00A61L24/08A61L31/04A61L31/14A61K9/06A61K47/36C08B37/08
CPCA61K9/06A61K47/36A61L24/0031A61L24/0042A61L24/08A61L31/042A61L31/145A61L31/148A61L2400/06C08B37/003C08L5/08
Inventor 魏长征钱锵王晓彤蒋丽霞
Owner SHANGHAI QISHENG BIOLOGICAL PREPARATION CO LTD
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