Gel prepared from chitosan or chitosan derivatives by multi-crosslinking and preparation method

A technology of chitosan derivatives and chitosan gel, which can be used in prosthesis, surgery, medical science, etc., and can solve the problems of biocompatibility and soft tissue matching.

Active Publication Date: 2017-11-07
IMEIK TECH DEV CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In addition, although CN201410141716.3 proposes that water-soluble epoxy compounds such as 1,4-butanediol diglycidyl ether or 1,2,7,8-dioxoctane can be used as chemical crosslinking agents, the patent More emphasis on physical and chemica

Method used

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  • Gel prepared from chitosan or chitosan derivatives by multi-crosslinking and preparation method

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Experimental program
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Effect test

Embodiment 1

[0031] Embodiment 1: the preparation of double cross-linked chitosan gel

[0032] Weigh 30.0 g of chitosan powder (deacetylation degree 85%, molecular weight 20 KDa), dissolve in 100 mL of 0.1 mol / L hydrochloric acid solution, heat up to 30 °C, stir for 1 h, and obtain a mass concentration of 300 mg / mL Chitosan hydrochloric acid solution. Chitosan hydrochloric acid solution was cooled to 0°C, 15 mL of β-glycerophosphate sodium solution with a mass concentration of 500 mg / mL was added dropwise, and the stirring was continued for 2 hours. After the stirring was completed, the pH value of the solution was about 7.3. Add 3.0 g of BDDE (1,4-butanediol glycidyl ether) to the solution (the mass ratio of BDDE to chitosan is 0.1:1), and stir for 30 minutes. After the stirring was completed, the temperature was raised to 15° C. for 24 hours to obtain a cross-linked chitosan gel. Take out the cross-linked chitosan gel, adopt the T 65 basic ULTRA-TURRAX® type disperser of IKA company to...

Embodiment 2

[0033] Embodiment 2: the preparation of triple cross-linked carboxymethyl chitosan gel

[0034] Weigh 25.0 g of carboxymethyl chitosan powder (deacetylation degree 85%, carboxymethyl substitution degree 1.1, molecular weight 80 KDa), dissolve it in 100 mL 0.1 mol / L sodium hydroxide solution, stir for 1 h, and obtain the mass Carboxymethyl chitosan alkaline solution with a concentration of 250 mg / mL. Under the condition of 25 ℃, the pH value of the carboxymethyl chitosan solution was adjusted to about 8.0 with a hydrochloric acid solution with a concentration of 2.0 mol / L. Add 5.0 g of BDDE (the mass ratio of BDDE to chitosan is 0.2:1) into the solution and stir for 30 minutes. After the stirring was completed, the temperature was kept at 25° C. for 18 hours to obtain a cross-linked carboxymethyl chitosan gel. Take out the cross-linked carboxymethyl chitosan gel, adopt the T 65 digital ULTRA-TURRAX® Package type disperser of IKA company to pulverize the gel under the rotation...

Embodiment 3

[0035] Embodiment 3: the preparation of five times cross-linked hydroxybutyl chitosan gel

[0036] Weigh 20.0 g of hydroxybutyl chitosan powder (deacetylation degree 90%, carboxymethyl substitution degree 1.5, molecular weight 100 KDa), dissolve it in 100 mL 0.1 mol / L sodium hydroxide solution, stir for 1 h, and obtain the mass Hydroxybutyl chitosan alkaline solution with a concentration of 200 mg / mL. Under the condition of 25 ℃, use the hydrochloric acid solution with the concentration of 1.0 mol / L to adjust the pH value of the hydroxybutyl chitosan solution to about 7.8. Add 5.0 g of DEO (1,2,7,8-diepoxyoctane) to the solution (the mass ratio of DEO to chitosan is 0.4:1), and stir for 30 minutes. After the stirring was completed, the temperature was kept at 25° C. for 18 hours to obtain a cross-linked hydroxybutyl chitosan gel. Take out the cross-linked hydroxybutyl chitosan gel, adopt the T 65 digital ULTRA-TURRAX® Package type disperser of IKA company to pulverize the ge...

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Abstract

The invention relates to gel prepared from chitosan or chitosan derivatives by multi-crosslinking and a preparation method. By multi-crosslinking chitosan or the chitosan derivatives, the elasticity modulus and the viscous modulus of the gel are increased and the swelling degree of the gel is reduced under the condition that the crosslinking degree of the gel is not increased. The elasticity modulus and the viscous modulus of the chitosan gel can be further increased each time one crosslinking is increased in the multi-crosslinking process, and the viscoelastic modulus of the gel can be increased by multi-crosslinking under the condition of equal crosslinking degree. The crosslinking times of the chitosan gel are selected according to characteristics of the viscoelastic modulus of different tissue parts, so that the viscoelastic modulus of the chitosan gel is matched with the related tissue, the histocompatibility of the gel in the tissue can be improved, and the use quantity of a crosslinking agent which is irritant or toxic to a human body can be reduced. The gel is applied to the field of soft tissue in tissue engineering such as tissue filling and repair, joint viscoelasticity replenishers, biological scaffolds, anti-cicatricial, anti-adhesion and biological glue and the like.

Description

technical field [0001] The invention relates to a chitosan or its derivative multiple cross-linked gel and a preparation method. Adopt this method, the speed that forms cross-linked chitosan gel is faster, guarantees that the degradation of chitosan in cross-linking reaction is slower, improved the utilization rate of cross-linking agent simultaneously, under the same situation of cross-linking degree, Multiple cross-linking can increase the viscoelastic modulus of the gel and reduce the use of cross-linking agents that are irritating or toxic to the human body. The chitosan gel prepared by the method has mechanical properties and rheological properties similar to those of human soft tissues, and has the advantages of good biocompatibility, high biosafety, degradability in vivo, and the like. The invention can be applied to the field of soft tissue in tissue engineering, including tissue filling and repair, joint viscoelastic supplement, biological scaffold, anti-scar and ant...

Claims

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Application Information

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IPC IPC(8): C08J3/24A61L27/20A61L27/58A61L27/52A61L27/50A61L31/04A61L31/14
Inventor 简军李睿智
Owner IMEIK TECH DEV CO LTD
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