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Cross-linked hyaluronic acid gel microparticle and preparation method thereof

A technology of cross-linking hyaluronic acid and hyaluronic acid, which is applied in the field of medical plastic surgery, can solve the problems that the dense structure is not conducive to the removal of residual cross-linking agents, affects the degradation time, and affects the operator's comfort, so as to reduce cross-linking The effect of reducing agent residue, increasing specific surface area, and ensuring safety

Active Publication Date: 2014-12-10
SHAANXI BIO REGENERATIVE MEDICINE CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] In summary, the particle size of the gel particle product obtained by the prior art technology determines the elastic modulus, affects the degradation time in vivo, and affects the comfort of the operator, and the dense structure is not conducive to the removal of the residual crosslinking agent. remove

Method used

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  • Cross-linked hyaluronic acid gel microparticle and preparation method thereof
  • Cross-linked hyaluronic acid gel microparticle and preparation method thereof
  • Cross-linked hyaluronic acid gel microparticle and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0051] Step 1, preparation of cross-linked hyaluronic acid gel:

[0052] 1. Weigh 1g of hyaluronic acid raw material;

[0053] 2. Add 1,4-butanediol diglycidyl ether, a cross-linking agent with 3% mass of hyaluronic acid raw material, to 15 ml of sodium hydroxide solution with a pH value of 11, and mix well to obtain solution A;

[0054] 3. Then dissolve the hyaluronic acid raw material in solution A, and after homogeneous stirring, obtain a hyaluronic acid sodium hydroxide gel with a concentration of 67 mg / ml;

[0055] 4. Then place it in a water bath at 65°C for a cross-linking reaction for 1.5 hours to obtain a cross-linked hyaluronic acid gel. Step 2, preparation of dehydration cross-linked hyaluronic acid film:

[0056] 1. Put the cross-linked hyaluronic acid gel obtained in step 1 into a roller press, and extrude it into a cross-linked hyaluronic acid gel film with a thickness of 0.1 mm.

[0057] 2. Dialyze the cross-linked hyaluronic acid gel film in 0.1g / L disodium ...

Embodiment 2

[0069] Step 1, preparation of cross-linked hyaluronic acid gel:

[0070] 1. Weigh 1g of hyaluronic acid raw material;

[0071] 2. Add ethylene glycol diglycidyl ether, a cross-linking agent with a mass of 1% hyaluronic acid raw material, to 10 ml of potassium hydroxide solution with a pH value of 13, and mix well to obtain solution A;

[0072] 3. Then dissolve the hyaluronic acid raw material in solution A, and after homogeneous stirring, obtain a hyaluronic acid potassium hydroxide gel with a concentration of 100 mg / ml;

[0073] 4. Then place it in a water bath at 45°C for a cross-linking reaction for 3 hours to obtain a cross-linked hyaluronic acid gel.

[0074] Step 2, preparation of dehydration cross-linked hyaluronic acid film:

[0075] 1. Put the cross-linked hyaluronic acid gel obtained in step 1 into a roller press, and extrude it into a cross-linked hyaluronic acid gel film with a thickness of 0.3 mm.

[0076] 2. Dialyze the cross-linked hyaluronic acid gel film in...

Embodiment 3

[0087] Step 1, preparation of cross-linked hyaluronic acid gel:

[0088] 1. Weigh 1g of hyaluronic acid raw material;

[0089] 2. Add glycerol triglycidyl ether, a cross-linking agent with a mass of 5% hyaluronic acid raw material, to 12 ml of potassium hydroxide solution with a pH value of 9, and mix well to obtain solution A;

[0090] 3. Then dissolve the hyaluronic acid raw material in solution A, and after homogeneous stirring, obtain a hyaluronic acid potassium hydroxide gel with a concentration of 83 mg / ml;

[0091] 4. Then place it in a water bath at 50°C for 2.5 hours of cross-linking reaction to obtain a cross-linked hyaluronic acid gel. Step 2, preparation of dehydration cross-linked hyaluronic acid film:

[0092] 1. Put the cross-linked hyaluronic acid gel obtained in step 1 into a roller press, and extrude it into a cross-linked hyaluronic acid gel film with a thickness of 0.2mm;

[0093] 2. Place the cross-linked hyaluronic acid gel film in 0.3 g / L disodium hyd...

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Abstract

The invention relates to a cross-linked hyaluronic acid gel microparticle and a preparation method thereof. The preparation method of the cross-linked hyaluronic acid gel microparticle comprises the following steps of carrying out crosslinking reaction on natural hyaluronic acid in presence of a crosslinking agent to form a macromolecular interpenetrating network structure, carrying out extrusion and film-forming, carrying out dry dialysis on a film material, carrying out single-side secondary crosslinking and then drying to form a film, rehydrating for swelling, mechanically shearing and granulating to obtain the curly cylindrical microparticle of which the size of the long axis is 0.2mm-1.0mm and the curling diameter is 0.1mm-0.8mm. By virtue of the structural property of the cross-linked hyaluronic acid gel microparticle, the soft tissue filling effect can be achieved in long-acting and safe manners.

Description

technical field [0001] The invention belongs to medical plastic surgery technology, and relates to a gel particle and a preparation method thereof. Background technique [0002] Natural hyaluronic acid is a physiological substance, which is mostly used to fill the space supported by cells and collagen fibers, and has excellent water-locking and water-retaining functions. [0003] With the increase of age, the influence of external force extrusion traction and light radiation and other factors, the hyaluronic acid in the human skin is gradually lost, which in turn causes the reduction of dermal cells, collagen and elastic fibers and the collapse of the three-dimensional space of the parts, resulting in skin relaxation. Facial wrinkles appear. This problem can be effectively solved by injecting hyaluronic acid, but due to hyaluronidase, free radical degradation and other reasons, the exogenous natural hyaluronic acid can be maintained in the body for a short time, which limit...

Claims

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Application Information

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IPC IPC(8): C08J3/24C08J3/075C08J3/12C08J5/18B29B9/00C08L5/08
Inventor 宋坤刘博文刘影张海龙卫方琦
Owner SHAANXI BIO REGENERATIVE MEDICINE CO LTD