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Preparation method of single-phase cross-linked sodium hyaluronate gel

A technology for cross-linking hyaluronic acid and sodium hyaluronate, applied in the field of pharmaceutical preparation, can solve the problems of unstable quality control, influence of gel properties, influence of product quality, etc., so as to reduce the risk of cross-contamination, ensure quality, reduce The effect of human manipulation

Inactive Publication Date: 2021-03-12
HYAMED BIOTECHNOLOGY (ZHUHAI) CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0003] At present, the existing preparation process of sodium hyaluronate generally includes the following steps: cross-linking reaction-swelling-dialysis-filling-sterilization, the main problems are as follows: by-products are easily produced during the cross-linking process, It is easy to produce air bubbles in the medium, which is easy to affect the properties of the gel, and the quality control is unstable, which seriously affects the quality of the product

Method used

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  • Preparation method of single-phase cross-linked sodium hyaluronate gel
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  • Preparation method of single-phase cross-linked sodium hyaluronate gel

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preparation example Construction

[0023] A preparation method of single-phase cross-linked sodium hyaluronate gel, which comprises the following steps:

[0024] S1. Add the cross-linking agent BDDE and NaOH solution in a centrifuge tube at a mass ratio of 1:8-1:10, and then put nitrogen into it and mix it in a centrifuge to obtain a NaOH mixture containing the cross-linking agent BDDE. solution, spare;

[0025] S2. Mix sodium hyaluronate and NaOH solution with pH>13 in a polytetrafluoroethylene cup with a cover at a mass ratio of 1:6-1:8, stir and dissolve, cover the cup and place it in a three-dimensional Mix in a mixer for 1-2 hours to obtain a sodium hyaluronate solution; wherein, the molecular weight of the sodium hyaluronate is 2.1-2.7 MDa;

[0026] S3. Add all the NaOH mixed solution prepared in step S1 into the sodium hyaluronate solution, mix well, and then pass nitrogen gas, so that the air in the cup is completely replaced by nitrogen gas, then cover the cup, and put it in a constant temperature wat...

Embodiment 1

[0030] A preparation method of single-phase cross-linked sodium hyaluronate gel, which comprises the following steps:

[0031] S1. Add 700 μL of cross-linking agent BDDE and 5 g of NaOH solution to a centrifuge tube, pass nitrogen gas into it, and mix in a centrifuge to obtain a NaOH mixed solution containing cross-linking agent BDDE, which is set aside;

[0032] S2. Take 10 g of sodium hyaluronate powder with a molecular weight of 2.1 MDa and dissolve it in 90 g of 0.3 mol / L sodium hydroxide solution in a PTFE beaker, then stir and dissolve it on a three-dimensional mixer at a speed of 70 rpm;

[0033] S3. After fully stirring and dissolving, add NaOH mixed solution, stir evenly, inject nitrogen gas into the cup and immediately cover the cup and transfer it to a constant temperature water bath at 45°C for 3 hours to obtain sodium hyaluronate gel;

[0034] S4. Cut the gel into small pieces of 0.5×0.5cm, add 9g of 3mol / L hydrochloric acid and 160g of PBS solution, place it on a...

Embodiment 2

[0037] A preparation method of single-phase cross-linked sodium hyaluronate gel, which comprises the following steps:

[0038] S1. Add 700 μL of cross-linking agent BDDE and 5 g of NaOH solution to a centrifuge tube, pass nitrogen gas into it, and mix in a centrifuge to obtain a NaOH mixed solution containing cross-linking agent BDDE, which is set aside;

[0039] S2. Take 10 g of sodium hyaluronate powder with a molecular weight of 2.5 MDa and dissolve it in 90 g of 0.3 mol / L sodium hydroxide solution in a PTFE beaker, then stir and dissolve it on a three-dimensional mixer at a speed of 70 rpm;

[0040] S3. After fully stirring and dissolving, add NaOH mixed solution, stir evenly, inject nitrogen gas into the cup and immediately cover the cup and transfer it to a constant temperature water bath at 50°C for 2 hours to obtain sodium hyaluronate gel;

[0041]S4. Cut the gel into small pieces of 0.5×0.5cm, add 9g of 3mol / L hydrochloric acid and 160g of PBS solution, place it on a ...

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Abstract

The invention discloses a preparation method of single-phase cross-linked sodium hyaluronate gel, and belongs to the technical field of medicine preparation. The preparation method comprises the following steps: preparing a NaOH mixed solution containing a cross-linking agent, preparing a sodium hyaluronate solution, adding the NaOH mixed solution into the sodium hyaluronate solution, uniformly stirring, and carrying out constant-temperature water bath to obtain the sodium hyaluronate gel; cutting the sodium hyaluronate gel into small blocks, adding the blocks into a hydrochloric acid PBS solution, and dialyzing in the PBS solution to obtain cross-linked phase sodium hyaluronate; and mixing the cross-linked phase sodium hyaluronate with the non-cross-linked phase sodium hyaluronate solution, and performing degassing, filling and sterilizing to obtain the product. According to the preparation method, manual operation in the production process can be effectively reduced, the risk of cross contamination is reduced, by-products can be avoided, bubbles generated in the filling process are effectively reduced, and therefore the quality of the sodium hyaluronate gel is effectively guaranteed.

Description

technical field [0001] The invention relates to the technical field of medicine preparation, in particular to a preparation method of single-phase cross-linked sodium hyaluronate gel. Background technique [0002] Hyaluronic acid is an important component of human and animal skin, vitreous, joint lubricating fluid and cartilage tissue, which consists of (1-β-4) D-glucuronic acid and (1-β-3) N-acetyl-D -Glucosamine disaccharide units are repeatedly connected, and are widely used in repair surgery, eye surgery or as cosmetic products to fill wrinkles. Hyaluronic acid has good physical and chemical properties and biocompatibility. However, it is rapidly degraded by the enzymatic hydrolysis of hyaluronidase in the body, and its retention time is short, requiring repeated injections to achieve curative effect. Cross-linked hyaluronic acid is a polymer gel obtained by cross-linking and modifying hyaluronic acid with a cross-linking agent, which can make up for the shortcomings o...

Claims

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Application Information

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IPC IPC(8): C08J3/24C08J3/075C08L5/08C08K5/1515
CPCC08B37/0072C08J3/075C08J3/24C08J2305/08C08K5/1515C08L5/08
Inventor 王师亮王江田
Owner HYAMED BIOTECHNOLOGY (ZHUHAI) CO LTD