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Double-crosslinked hyaluronic acid hydrogel as well as preparation method and application thereof

A technology of hyaluronic acid and double cross-linking, applied in medical science, prosthesis, surgery, etc., can solve the problems of poor water solubility, poor mechanical properties, and cytotoxicity of photoinitiators, and achieve improved mechanical properties and fast gelation speed , little cytotoxic effect

Active Publication Date: 2020-06-09
SUZHOU INST OF NANO TECH & NANO BIONICS CHINESE ACEDEMY OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, the photoinitiator used in this scheme has poor water solubility, has certain toxicity to cells, and has poor mechanical properties, and the maximum compressive stress is only about 160kPa.

Method used

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  • Double-crosslinked hyaluronic acid hydrogel as well as preparation method and application thereof
  • Double-crosslinked hyaluronic acid hydrogel as well as preparation method and application thereof
  • Double-crosslinked hyaluronic acid hydrogel as well as preparation method and application thereof

Examples

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preparation example Construction

[0025] In some embodiments, the preparation method of the double-crosslinked hyaluronic acid hydrogel comprises:

[0026] Modify hyaluronic acid with modifiers to obtain double bonded hyaluronic acid;

[0027] In the presence of a cross-linking agent and a photoinitiator, the double-bonded hyaluronic acid is subjected to physical cross-linking and photochemical cross-linking reactions, thereby obtaining a double-cross-linked hyaluronic acid hydrogel, wherein the cross-linking agent Including tannic acid, the photoinitiator can be lithium phenyl (2,4,6-trimethylbenzoyl) phosphate (LAP), 2-hydroxy-4'-(2-hydroxyethoxy)- Any one or a combination of two or more of 2-methylpropiophenone (photoinitiator 2959) and 1-hydroxycyclohexyl phenylketone (photoinitiator 184), but not limited thereto.

[0028] In some preferred embodiments, the modifying agent may include any one or a combination of two or more of 2-methacrylic anhydride, acrylic anhydride, maleic anhydride, etc., but is not ...

Embodiment 1

[0061] This embodiment provides a method for preparing a double-crosslinked hyaluronic acid hydrogel, which includes the following steps:

[0062] (1) Preparation of double bonded hyaluronic acid:

[0063] Hyaluronic acid aqueous solution:

[0064] A hyaluronic acid aqueous solution with a mass concentration of 0.005 g / ml is prepared by mixing hyaluronic acid and deionized water.

[0065] Double bonded hyaluronic acid:

[0066] Mix 2-methacrylic anhydride with hyaluronic acid aqueous solution at a molar ratio of 3:1 to the repeating units contained in hyaluronic acid, then use NaOH solution to adjust the pH value to 8, and react at 4°C for 20 hours. After the end, the reaction system was dialyzed and freeze-dried in sequence to obtain double-bonded hyaluronic acid. The structural formula of double-bonded hyaluronic acid is as follows:

[0067] where n is 125-2500.

[0068] Wherein, the dialysis is dialysis with deionized water for 5 days, freeze-drying for 3 days, and th...

Embodiment 2

[0074] This example provides a preparation method of double-crosslinked hyaluronic acid hydrogel, which is roughly the same as the preparation method provided in Example 1, the difference lies in the preparation of double-crosslinked hyaluronic acid hydrogel, the difference is as follows :

[0075] Mix double-bonded hyaluronic acid, tannic acid solution, and phenyl (2,4,6-trimethylbenzoyl) phosphate lithium salt (photoinitiator) at a volume ratio of 8:1:1; The concentration of the bonded hyaluronic acid solution is 0.02g / ml, the concentration of the tannic acid solution is 0.04g / ml, and the concentration of the photoinitiator is 0.008g / ml.

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Abstract

The invention discloses double-crosslinked hyaluronic acid hydrogel as well as a preparation method and application thereof. The preparation method comprises the steps: carrying out modification treatment on hyaluronic acid by using a modifier to obtain double-bonded hyaluronic acid; and in the presence of a cross-linking agent and a photoinitiator, carrying out physical cross-linking and photochemical cross-linking reactions on the double-bonded hyaluronic acid to obtain the double-crosslinked hyaluronic acid hydrogel. The double-crosslinked hyaluronic acid hydrogel disclosed by the inventionhas good mechanical properties, and the hyaluronic acid derivative in the whole scheme is self-crosslinked, so that introduction of other macromolecular chains is effectively avoided, and the problemthat the hyaluronic acid hydrogel is limited in practical application due to the fact that the hyaluronic acid hydrogel needs to be compounded with other macromolecular chain materials due to too lowstrength is solved; moreover, the photoinitiator with better water solubility and lower cytotoxicity is used, the gelling speed is high, the mechanical property of the obtained hydrogel is greatly improved through double crosslinking, and the maximum compression stress can reach 2.5 MPa or above.

Description

technical field [0001] The invention relates to a hydrogel material, in particular to a double-crosslinked hyaluronic acid hydrogel, its preparation method and application, and belongs to the technical field of biomaterials. Background technique [0002] Hydrogel is a multi-component system composed of a three-dimensional cross-linked network structure polymer and a medium. Because of its excellent properties such as water absorption, water retention, biocompatibility, and the ability to generate corresponding intelligent properties for stimuli, its application has penetrated into To agriculture, forestry, animal husbandry, horticulture, desert control, medical and health, biomedicine, construction, petrochemical, daily chemical, food, electronics and environmental protection and other fields, and is still expanding to a wider application field. [0003] Hyaluronic acid hydrogel has excellent properties such as inherent biocompatibility, high water absorption, injectability,...

Claims

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Application Information

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IPC IPC(8): C08J3/075C08J3/24C08J3/28C08L5/08A61L27/20A61L27/50A61L27/52A61L31/04A61L31/14
CPCC08J3/075C08J3/24C08J3/28A61L27/52A61L27/20A61L27/50A61L31/145A61L31/14A61L31/042C08J2305/08C08L5/08
Inventor 戴建武吴桐陈艳艳
Owner SUZHOU INST OF NANO TECH & NANO BIONICS CHINESE ACEDEMY OF SCI