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Polyethylene glycol-chitosan dual-network hydrogel as well as preparation method and application thereof

A polyethylene glycol and chitosan technology, applied in prosthesis, medical science and other directions, can solve the problems of cartilage repair effect that needs to be further improved, low mechanical strength, low cross-linking density, etc., to achieve good immune regulation characteristics, mechanical The effect of high strength and high crosslink density

Active Publication Date: 2022-08-05
PEKING UNIV THIRD HOSPITAL +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0005] Chinese patent application CN112646202A discloses a functionalized double-network hydrogel and its preparation method. The double-network hydrogel in this patent application is formed by interpenetrating a chitosan cross-linked network and a four-armed polyethylene glycol cross-linked network. , the chitosan cross-linked network is formed by cross-linking chitosan coupled with KGN; the four-arm polyethylene glycol cross-linked network is formed by chemical reaction of the first precursor and the second precursor, The first precursor is Tetra-PEG-NH 2 , the second precursor is Tetra-PEG-NHS, but the chitosan cross-linked network and the four-arm polyethylene glycol cross-linked network in this patent application are interspersed with each other, and the two are relatively independent, The force between each other is very small, which leads to the problems of low cross-linking density and low mechanical strength in the functionalized double network hydrogel in this patent application; in addition, the functionalized double network hydrogel in this patent application is also There are problems such as excessive swelling rate and cartilage repair effect that need to be further improved

Method used

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  • Polyethylene glycol-chitosan dual-network hydrogel as well as preparation method and application thereof
  • Polyethylene glycol-chitosan dual-network hydrogel as well as preparation method and application thereof
  • Polyethylene glycol-chitosan dual-network hydrogel as well as preparation method and application thereof

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preparation example Construction

[0044] In the first aspect, the present invention provides a preparation method of polyethylene-shell polycogen dual network hydrogel, which includes the following steps:

[0045] (1) KGN solution and Tetra-PEG-NH activated by EDCI / NHS 2 Reaction, get KGN-Tetra-Peg-NH 2 ; In the present invention, the step (1) is to make Tetra-PEG-NH 2 Puppet KGN, get KGN-TETRA-PEG-NH 2 In the present invention, KGN-Tetra-Peg-NH can also be used 2 Remember (kgn) x -Tetra-peg- (NH 2 Cure y Among them, x+y = 4, preferably, x / y = 0.02 ~ 2; the present invention by adjusting Tetra-Peg-NH 2 Compared with KGN's feeding, you can get different branches (KGN) x -Tetra-peg- (NH 2 Cure y It

[0046] (2) KGN-Tetra-Peg-NH 2 Formulating into the first solution; in step (2), the second solution is based on PBS solution (phosphate buffer solution) as the solvent. There is no special restriction on the concentration of the first solution of the first solution. The concentration of the first solution is 100 ~ 300mg...

Embodiment 1

[0080] ① KGN-TETRA-Peg-NH 2 Synthesis:

[0081] (A) KGN 120 mg, EDCI 726 mg, NHS 434.8 mg dissolved in 20 mL distilled water, regulate the pH value of the solution to 5.7, 37 ° C, stir at 2 h to obtain the KGN solution activated by EDCI / NHS;

[0082] (B) Terra-peg-nh 2 (Buy from Xiamen Sanoge, product number 06020700209, molecular weight 1W) 4000 mg is added to the above -mentioned KGN solution activated by EDCI / NHS, and further add distilled water to the overall volume of the solution to 150 ml. Then place the response product obtained after the reaction in the dialysis bag with a dialysis bag with an intercepting molecular weight to 1kd, and replace the distilled water every 12 hours to continue the dialysis 72h; x -Tetra-peg- (NH 2 Cure y Compounds (x / y = 0.28: 1), that is, KGN-Tetra-PEG-NH 2 Essence

[0083] ② Take the step ① obtained by the PBS solution (pH = 7.4) as the solvent ① 2 The first solution is prepared into a concentration of 200 mg / ml.

[0084] ③ Use the PBS solut...

Embodiment 2

[0087] Example 2 is basically the same as Example 1, the difference is:

[0088] ③ Use the PBS solution (pH = 7.4) as the solvent to make the shell polycanic concentration of 25 mg / ml shell polysaccharide solution, and according to the amino group and Tetra-PEG-NHS contained in the shell polysaccharide solution, The Moore of the regiment is 0.15: 1 The Tetra-PEG-NHS is called, and then the Tetra-Peg-NHS is added to the shell polycan solution for reaction. The reaction temperature is room temperature, and the response time is 120s to obtain the second solution.

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Abstract

The invention relates to polyethylene glycol-chitosan double-network hydrogel as well as a preparation method and application thereof, and belongs to the technical field of novel medical materials. The method comprises the following steps: enabling a KGN solution activated by EDCI / NHS to react with Tetra-PEG-NH2 to obtain KGN-Tetra-PEG-NH2, and preparing the KGN-Tetra-PEG-NH2 into a first solution; reacting the chitosan solution with Tetra-PEG-NHS (Polyethylene Glycol-Hydroxysuccinimide) for 10-300 seconds according to the molar ratio of amino to NHS of (0.01-0.25): 1, so as to obtain a second solution; mixing the first solution and the second solution according to the molar ratio of amino to NHS of (0.8-1.2): 1, standing to form gel, and activating to obtain the polyethylene glycol-chitosan double-network hydrogel. The hydrogel provided by the invention has the advantages of high mechanical strength, good cartilage induced differentiation microenvironment, good cartilage repair effect and the like.

Description

Technical field [0001] The present invention is a medical technology field, especially involving a polyethylene-shell polysaccharide dual-network hydrogel and its preparation methods and applications. Background technique [0002] Sports -related trauma or degenerative changes can cause cartilage injuries. Due to the characteristics of cartilage without blood vessels, nervous, no lymphatic vessels, low metabolic rates and low cell density, it is difficult to self -repair after the injury. At present, traditional clinical treatment methods mainly include arthroscopy cleaning, cartilage grinding molding, bone marrow stimulus technology, autologous or similar album cartilage transplantation, autologous cartilage cell transplantation, metal or silicone rubber transplantation, etc. , Limitation and deficiencies such as the complications of the supply body, the failure of the transplants, the dewlating of seed cells, and the loosening of alternatives. Fortunately, the organizational en...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C08J3/075C08J3/24C08L5/08C08L71/02A61L27/48A61L27/52
CPCC08J3/075C08J3/24A61L27/52A61L27/48A61L2430/06C08J2371/02C08J2405/08C08J2305/08C08J2471/02
Inventor 余家阔陈有荣王星颜昕叶景
Owner PEKING UNIV THIRD HOSPITAL
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