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Preparation method of sodium hyaluronate/sodium alginate injection type composite hydrogel

A technology of sodium hyaluronate and composite hydrogel, which is applied in the directions of non-active ingredients such as medical preparations, pharmaceutical formulas, prostheses, etc. The preparation method is simple and the application prospect is good.

Inactive Publication Date: 2019-11-26
BEIJING UNIV OF CHEM TECH
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, the cross-linking process of most chemical gels requires the addition of additional initiators, which often have high toxicity and specific triggering conditions, and are not suitable for in-situ use in vivo [Todd R.Hoare, DanielS.Kohane .Hydrogels in drug delivery:Progress and challenges.Polymer.2008;49:1993-2007.]
On the other hand, most of the curre

Method used

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  • Preparation method of sodium hyaluronate/sodium alginate injection type composite hydrogel
  • Preparation method of sodium hyaluronate/sodium alginate injection type composite hydrogel
  • Preparation method of sodium hyaluronate/sodium alginate injection type composite hydrogel

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Embodiment 1

[0043] A preparation method of sodium hyaluronate / sodium alginate injection type composite hydrogel constructed by Schiff base cross-linking reaction, the specific steps are as follows:

[0044] 1) Preparation of hyaluronic acid-adipic acid dihydrazide derivative (HA-ADH)

[0045] Put 2g HA (molecular weight 40KDa) solution in 400mL deionized water, then add 20g adipic acid dihydrazide and adjust the pH of the solution to 5.0-7.4 with hydrochloric acid, and further add 4.0g 1-ethyl-(3-dimethylaminopropyl) After carbodiimide (EDC), react overnight. Finally, the product HA-ADH solution is purified by dialysis (with a molecular weight cut-off of 8-10KDa dialysis bag) and then lyophilized for storage.

[0046] 2) Preparation of sodium alginate derivative (ALG-CHO)

[0047] Dissolve 2g of sodium alginate in 100ml of ultrapure water to form a 2% aqueous solution, and dissolve 1.1g of sodium periodate in 10ml of ultrapure water to form a solution; then add the sodium periodate solution to t...

Embodiment 2

[0051] A preparation method of sodium hyaluronate / sodium alginate injection type composite hydrogel constructed by Schiff base cross-linking reaction, the specific steps are as follows:

[0052] 1) Preparation of hyaluronic acid-adipic acid dihydrazide derivative (HA-ADH)

[0053] Put 2g HA (molecular weight 50 KDa) solution in 400mL deionized water, then add 30g adipic acid dihydrazide and adjust the pH of the solution to 5.0-7.4 with hydrochloric acid, and further add 6g 1-ethyl-(3-dimethylaminopropyl) After carbodiimide (EDC), react overnight. Finally, the product HA-ADH solution is purified by dialysis (with a molecular weight cut-off of 8-10KDa dialysis bag) and then lyophilized for storage.

[0054] 2) Preparation of sodium alginate derivative (ALG-CHO)

[0055] Dissolve 2g of sodium alginate in 200ml of ultrapure water to form a 1% aqueous solution, and take another 2g of sodium periodate dissolved in 20ml of ultrapure water to form a solution; then add the sodium periodate so...

Embodiment 3

[0059] A preparation method of sodium hyaluronate / sodium alginate injection type composite hydrogel constructed by Schiff base cross-linking reaction, the specific steps are as follows:

[0060] 1) Preparation of hyaluronic acid-adipic acid dihydrazide derivative (HA-ADH)

[0061] Put 4g HA (molecular weight 50KDa) solution in 400mL deionized water, then add 40g adipic acid dihydrazide and adjust the pH of the solution to 5.0-7.4 with hydrochloric acid, and further add 4.0g 1-ethyl-(3-dimethylaminopropyl) After carbodiimide (EDC), react overnight. Finally, the product HA-ADH solution is purified by dialysis (with a molecular weight cut-off of 8-10KDa dialysis bag) and then lyophilized for storage.

[0062] 2) Preparation of Sodium Alginate Derivatives (ALG-CHO) Take 2g of sodium alginate dissolved in 100ml of ultrapure water to form a 2% aqueous solution, and another 1.1g of sodium periodate dissolved in 10ml of ultrapure water to form Solution; Then add the sodium periodate soluti...

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Abstract

The invention discloses a preparation method of sodium hyaluronate/sodium alginate injection type composite hydrogel. The preparation method comprises the following steps: initiating a condensation reaction of amino of adipic dihydrazide and carboxyl of a main chain of hyaluronic acid (HA) through 1-ethyl-3-(3-dimethylamino)carbodiimide hydrochloride to obtain a hyaluronic acid-adipic dihydrazidederivative (HA-ADH) with a main chain having amino; oxidizing hydroxyl on sodium alginate through the strong oxidizing property of sodium periodate to obtain an aldehyde group-containing sodium alginate derivative (ALG-CHO); and mixing the HA-ADH with the ALG-CHO according to a certain ratio, and then carrying out a Schiff base reaction for chemical crosslinking to obtain the sodium hyaluronate/sodium alginate composite hydrogel. The preparation method is suitable for industrial large-scale production, and the degradation rate of the hydrogel can be effectively regulated and controlled by changing the composition ratio of the HA-ADH to the ALG-CHO. The sodium hyaluronate/sodium alginate Schiff base reaction hydrogel prepared by the method disclosed by the invention can be used as a novel injection type hydrogel to be applied to the field of biomedicine.

Description

Technical field [0001] The invention relates to a preparation method of an injection type hydrogel, in particular to a preparation method of a sodium hyaluronate / sodium alginate composite hydrogel. Background technique [0002] The broad application prospects of hydrogel materials in long-term sustained-release drug delivery, tissue repair and cell transplantation have quickly become one of the most popular research directions in the field of biomaterials. Injectable hydrogel, as a new type of material, can make up for the shortcomings of traditional hydrogels. It can be directly implanted into the tissue through a syringe, avoiding the destructive effects of pioneering surgery on the body tissues and reducing the difficulty of clinical application [Todd R. Hoare, Daniel S. Kohane. Hydrogels indrug delivery: Progress and challenges. Polymer. 2008; 49: 1993-2007.]. However, most of the injectable hydrogels currently researched and applied use physical association to trigger the f...

Claims

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Application Information

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IPC IPC(8): C08J3/075C08B37/04C08B37/08A61K47/36A61L27/52A61L27/48C08L5/08C08L5/04
CPCA61K47/36A61L27/48A61L27/52A61L2400/06C08B37/0072C08B37/0084C08J3/075C08J2305/04C08J2305/08C08J2405/04C08J2405/08
Inventor 张建军殷鹏
Owner BEIJING UNIV OF CHEM TECH
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