Hyaluronic acid and epsilon-polylysine cross-linking method, obtained composite cross-linked product and application

A technology of hyaluronic acid and polylysine, which is used in medical science, prosthesis, tissue regeneration, etc., can solve the problems of complex preparation process, achieve good biocompatibility, slow gel degradation rate, and simple and easy method. row effect

Active Publication Date: 2020-10-02
BLOOMAGE BIOTECHNOLOGY CORP LTD
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In this preparation method, hyaluronic acid first needs to be oxidized into aldehyde groups under the action of a strong oxidant, then a reaction terminator is added to terminate the oxidation reaction, and then the strong oxidant and reaction terminator ar

Method used

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  • Hyaluronic acid and epsilon-polylysine cross-linking method, obtained composite cross-linked product and application
  • Hyaluronic acid and epsilon-polylysine cross-linking method, obtained composite cross-linked product and application
  • Hyaluronic acid and epsilon-polylysine cross-linking method, obtained composite cross-linked product and application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0029] Example 1 Effect of the amount of coupling agent and auxiliary coupling agent on the degree of crosslinking between hyaluronic acid and ε-polylysine

[0030](1) Preparation of reaction solution: at room temperature, add coupling agent, auxiliary coupling agent and 1.6g ε-polylysine hydrochloride to 100ml deionized water in sequence, and dissolve completely. Use NaOH solution to adjust the pH value to 9.0, then add 5g of hyaluronic acid (1.42╳10 6 Da) for dissolution.

[0031] (2) Cross-linking reaction: Put the above-prepared reaction solution at 4°C for 10-30 min and activate it for 10-30 min, then take it out and place it at room temperature for 4 h to get a transparent cross-linked composite gel.

[0032] (3) Dialysis: After the reaction, soak the cross-linked composite gel in deionized water and wash to remove uncross-linked reactants.

[0033] (4) Freeze-drying: Finally, freeze-dry to obtain a composite cross-linked product of hyaluronic acid and ε-polylysine.

...

Embodiment 2

[0048] Example 2 Effect of pH on the degree of crosslinking between hyaluronic acid and ε-polylysine

[0049] (1) Preparation of reaction solution: Add 3.59g of EDC, 2.16g of NHS and 1.6g of ε-polylysine hydrochloride to 100ml of deionized water at room temperature, and dissolve completely. Use HCl solution or NaOH solution to adjust the pH value to 2.0~12.0, then add 5g hyaluronic acid (1.42╳10 6 Da) for dissolution.

[0050] (2) Cross-linking reaction: Put the above-prepared reaction solution at 4°C for 10-30 minutes to activate, then take it out and place it at room temperature for 8 hours of cross-linking reaction to obtain a transparent cross-linked composite gel.

[0051] (3) Dialysis: After the reaction, soak the cross-linked composite gel in deionized water and wash to remove uncross-linked reactants.

[0052] (4) Freeze-drying: Finally, freeze-dry to obtain a composite cross-linked product of hyaluronic acid and ε-polylysine.

[0053] Under the reaction conditions ...

Embodiment 3

[0056] Example 3 Effect of Different Molecular Weights of Hyaluronic Acid on the Crosslinking Degree of Hyaluronic Acid and ε-Polylysine

[0057] (1) Preparation of reaction solution: Add 3.59g of EDC, 2.16g of NHS and 1.6g of ε-polylysine hydrochloride to 100ml of deionized water at room temperature, and dissolve completely. The pH value was adjusted to 9.0 with NaOH solution, and then 5 g of hyaluronic acid was added to the above solution for dissolution while stirring.

[0058] (2) Cross-linking reaction: Put the above-prepared reaction solution at 4°C for 10-30 minutes to activate, then take it out and place it at room temperature for 2 hours of cross-linking reaction to obtain a transparent cross-linked composite gel.

[0059] (3) Dialysis: After the reaction, soak the cross-linked composite gel in deionized water and wash to remove uncross-linked reactants.

[0060] (4) Freeze-drying: Finally, freeze-dry to obtain a composite cross-linked product of hyaluronic acid and ...

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Abstract

The invention discloses a hyaluronic acid and epsilon-polylysine cross-linking method, an obtained composite cross-linked product and an application. The method includes subjecting hyaluronic acid orsalt thereof and epsilon-polylysine or salt thereof to a cross-linking reaction in condition of a coupling agent, an auxiliary coupling agent and a neutral or alkaline water environment to obtain thecomposite cross-linked product. According to the method, protonation of epsilon-polylysine or salt thereof is inhibited in a neutral or alkaline environment, so that carboxyl of hyaluronic acid or salt thereof and amino of epsilon-polylysine or salt thereof are subjected to amidation reaction, and flocculating settling is inhibited or avoided. The hyaluronic acid or the salt thereof is crosslinkedwith the epsilon-polylysine or the salt thereof, the epsilon-polylysine or the salt thereof is equivalent to a cross-linking agent, catabolism of the epsilon-polylysine or the salt thereof in vivo can be absorbed and utilized by a human body, the biocompatibility is good, and cytotoxicity easily caused by a traditional cross-linking agent can be avoided.

Description

technical field [0001] The invention relates to a method for cross-linking hyaluronic acid and ε-polylysine, in particular to a method for preparing a composite cross-linked product of hyaluronic acid and ε-polylysine, as well as the obtained product and its application. Background technique [0002] Hyaluronic acid is a naturally occurring polyanionic mucopolysaccharide, which is a linear polymer composed of repeating disaccharide units composed of D-glucuronic acid and D-N-acetylglucosamine. Hyaluronic acid widely exists in living organisms and has excellent biocompatibility, so it is an ideal natural polymer medical material. However, hyaluronic acid is easily degraded by enzymes in the human body, resulting in a short half-life in the body. In order to prolong the residence time of hyaluronic acid in the body, a lot of modification and cross-linking of hyaluronic acid have been carried out. [0003] ε-polylysine (ε-PL) is a lysine homopolymer produced by microbial ferm...

Claims

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Application Information

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IPC IPC(8): C08J3/24C08L77/04C08L5/08A61L27/58A61L27/50A61L27/26A61L27/54
CPCC08J3/246A61L27/58A61L27/50A61L27/26A61L27/54C08J2305/08C08J2377/04C08J2477/04A61L2430/06A61L2300/412A61L2300/404C08L77/04C08L5/08
Inventor 王冠凤石艳丽钱晓路董艳美郭学平
Owner BLOOMAGE BIOTECHNOLOGY CORP LTD
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