A composition containing hyaluronate and its preparation method

A technology of hyaluronic acid salt and hyaluronic acid, which is applied in the field of hyaluronic acid double gel system and its preparation, can solve the problem of high viscosity of cross-linked hyaluronic acid gel, prone to skin mounds, nodules, and low fluidity and other problems, to achieve the effect of long acting time in the body, easy to push and operate, and enhanced fluidity

Active Publication Date: 2022-04-19
BLOOMAGE BIOTECHNOLOGY CORP LTD +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, cross-linked hyaluronic acid gel has problems such as high viscosity and low fluidity, and it is filled in a pre-filled syringe with high pushing force. layer, prone to symptoms such as skin mounds and nodules

Method used

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  • A composition containing hyaluronate and its preparation method

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preparation example Construction

[0068] The present invention also provides a preparation method of a hyaluronate-containing composition, the method comprising:

[0069] preparing a cross-linked hyaluronate gel using the first hyaluronic acid or hyaluronate;

[0070] using a second hyaluronic acid or hyaluronate to prepare a non-crosslinked hyaluronate gel;

[0071] The cross-linked hyaluronate gel and the non-cross-linked hyaluronate gel are mixed and then subjected to high temperature treatment to obtain a double gel system.

[0072] Specifically, the preparation of cross-linked hyaluronate gel includes:

[0073] Dissolve hyaluronic acid or hyaluronate in an alkaline solution containing a crosslinking agent, and react for 5-30 hours at 20-35°C;

[0074] Water was added to swell the gel piece and dialyzed to remove unreacted cross-linking agent and base.

[0075] Specifically, the molecular weight of the first hyaluronic acid or hyaluronate is 1 million Daltons to 2.5 million Daltons, for example, it can ...

Embodiment 1

[0093] Take 20g of sodium hyaluronate with a molecular weight of 1.8 million Daltons, dissolve it in 100mL solution containing 0.4g BDDE and 0.4g sodium hydroxide, and react at 25°C for 24h; cut the gel into about 1cm 3 Granules, add phosphate buffer (concentration is 0.3mg / mL concentration, pH value is 6.0-8.0) make gel block swelling, dialyze, remove unreacted cross-linking agent and alkali, control hyaluronic acid concentration to be 1.5%, The gel has a pH value of 6.0-8.0, and passes through a 120-mesh stainless steel screen to obtain a cross-linked sodium hyaluronate gel.

[0094] Take 1.0 g of sodium hyaluronate with a molecular weight of 800,000 Daltons, add it to 100 mL of 0.5% glycerin aqueous solution, stir until dissolved, and filter through a 5 μm filter element to obtain non-crosslinked sodium hyaluronate gel with a pH of 6.0-8.0. glue.

[0095] The sodium hyaluronate gel and the non-crosslinked sodium hyaluronate gel were mixed at a mass ratio of 1:10, and after...

Embodiment 2

[0103] Take 20 g of sodium hyaluronate with a molecular weight of 1.2 million Daltons, dissolve it in 100 mL of a solution containing 1.0 g of BDDE and 0.6 g of sodium hydroxide, and react at 25° C. for 24 hours. Cut the gel into about 1cm 3 Granules, add phosphate buffer (concentration is 0.3mg / mL, pH value is 6.5) to make the gel piece swell, remove unreacted cross-linking agent and alkali through dialysis 3-6 times, control the hyaluronic acid concentration to be 1.5 %, the pH value of the gel is 6.0-8.0, and passed through a 120-mesh stainless steel screen to obtain a cross-linked sodium hyaluronate gel.

[0104] Take 1.0 g of sodium hyaluronate with a molecular weight of 100,000 daltons and 0.5 g of sodium hyaluronate with a molecular weight of 1 million daltons, add them to 100 mL of 0.5% glycerin aqueous solution, stir until dissolved, and filter through a 5 μm filter element to obtain pH 6.0-8.0 non-cross-linked sodium hyaluronate gel.

[0105] The sodium hyaluronate...

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Abstract

The present invention provides a hyaluronate-containing composition comprising a two-gel system composed of a cross-linked hyaluronate gel and a non-cross-linked hyaluronate gel, the pH of the two-gel system 6.0-8.0, the average particle size is 100-300μm, and the kinematic viscosity is 10-80mm 2 / s, the pushing force is 5‑30N. The present invention also provides a method for preparing a hyaluronate-containing composition, comprising: using the first hyaluronic acid or hyaluronate to prepare a cross-linked hyaluronate gel; using the second hyaluronic acid or hyaluronate Hyaluronate to prepare non-cross-linked hyaluronate gel; mixing the cross-linked hyaluronate gel and the non-cross-linked hyaluronate gel, followed by high temperature treatment to obtain a double gel system. Compared with traditional hyaluronic acid water-light products, the composition prepared by the present invention has enhanced anti-hyaluronidase ability, longer in vivo action time, low gel viscosity, high slip, enhanced fluidity, and easier clinical use. Pushing operation can reduce side effects such as skin bumps and redness.

Description

technical field [0001] The invention relates to the technical field of hyaluronic acid, in particular to a hyaluronic acid double gel system and its preparation method and application. Background technique [0002] Hyaluronic acid is a straight-chain macromolecular acidic mucopolysaccharide composed of D-glucuronic acid and N-acetylglucosamine disaccharide units, also known as hyaluronic acid, which widely exists in humans, animals, and microorganisms without species specificity Non-toxic, non-irritating, good biocompatibility and high safety. Various parts of the human body, such as articular cartilage, lens, skin dermis and other tissues contain hyaluronic acid, and the hyaluronic acid contained in the skin accounts for more than half of the total hyaluronic acid in the human body. As people age, the content of hyaluronic acid in human skin gradually decreases, and the reduction of hyaluronic acid makes the skin gradually lose its elasticity, making the skin rough and dul...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C08L5/08C08J3/075
CPCC08L5/08C08J3/075C08J2305/08C08J2405/08
Inventor 李霞王玉玲郭学平王启明魏健耿凤
Owner BLOOMAGE BIOTECHNOLOGY CORP LTD
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