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A method to guide the structural rearrangement of cross-linked sodium hyaluronate gel

A technology of cross-linking hyaluronic acid and sodium hyaluronate, which is applied in the field of medical biomaterials to achieve the effects of not being easily collapsed, good viscoelasticity and cohesion, and protecting the integrity of the molecular structure

Active Publication Date: 2021-10-01
SHANGHAI QISHENG BIOLOGICAL PREPARATION CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, so far, there is no patent related to the method of using stress to guide the rearrangement of the molecular structure of sodium hyaluronate to regulate its cross-linking process

Method used

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  • A method to guide the structural rearrangement of cross-linked sodium hyaluronate gel
  • A method to guide the structural rearrangement of cross-linked sodium hyaluronate gel

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0024] Weigh 1 g of sodium hyaluronate dry powder with a molecular weight of 1.3 million Da, dissolve it in 2% sodium hydroxide solution, and prepare a sodium hyaluronate solution with a concentration of 2.4% (m / m). Take 150 μl of divinyl sulfone, dissolve it in 2% sodium hydroxide solution, and prepare a cross-linking agent solution with a concentration of 1.8% (v / v). The sodium hyaluronate solution and the cross-linking agent solution prepared above were injected into microchannels A and B respectively, and the flow rates of the two were adjusted to 60 m / min and 10 m / min, respectively. After the solutions of the two channels enter the mixing channel, they continue to flow at a flow rate of 60 m / min for 15 minutes, and the temperature of the channel is 40°C. Then the preliminarily cross-linked sodium hyaluronate was drained into the cross-linking tank, heated in a water bath at 40° C., and mechanically stirred at 100 rpm for 2 hours. After the reaction is finished, slowly ad...

Embodiment 2

[0027] Weigh 1g of sodium hyaluronate dry powder with a molecular weight of 1.3 million Da, dissolve it in 2% sodium hydroxide solution, and prepare a sodium hyaluronate solution with a concentration of 2.0% (m / m), to which divinyl 150 μl of sulfone, heated in a water bath at 40°C, and mechanically stirred at 100 rpm for 2 hours and 15 minutes. After the reaction is finished, slowly add 95% ethanol solution until a white precipitate is precipitated. The white precipitate is washed 5 to 10 times with the same concentration of ethanol solution, and then filtered to obtain a white powder; the white powder is dissolved in 50ml of PBS solution, dialyzed A cross-linked sodium hyaluronate gel was obtained.

[0028] The gel prepared above was freeze-dried, quenched with liquid nitrogen, and the section of the gel was observed by a scanning electron microscope. like figure 2 As shown, the gel presents an isotropic porous structure.

[0029] Compared with Example 1, under the same c...

Embodiment 3

[0031] Weigh 1 g of sodium hyaluronate dry powder with a molecular weight of 1.7 million Da, dissolve it in 2% sodium hydroxide solution, and prepare a sodium hyaluronate solution with a concentration of 2.0% (m / m). Draw 180 μl of divinyl sulfone, dissolve it in 2% sodium hydroxide solution, and prepare a cross-linking agent solution with a concentration of 1.5% (v / v). The sodium hyaluronate solution and cross-linking agent solution prepared above were injected into microchannels A and B respectively, and the flow rates of the two were adjusted to 80 m / min and 15 m / min, respectively. After the solutions of the two channels enter the mixing channel, they continue to flow at a flow rate of 80 m / min for 8 minutes, and the temperature of the channel is 45°C. Then the preliminarily cross-linked sodium hyaluronate was drained into the cross-linking tank, heated in a water bath at 45° C., and mechanically stirred at 100 rpm for 3 hours. After the reaction is finished, slowly add 95%...

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Abstract

The invention relates to a method for guiding the structural rearrangement of cross-linked sodium hyaluronate gel. In this method, sodium hyaluronate and cross-linking agent solution are respectively injected into different microchannels, the flow rate of the two is controlled to enter the mixing channel, and the initial cross-linking reaction occurs through the continuous flow, and then the product is drained into the cross-linking pool to continue cross-linking. After linking to the end point, after alkalization, precipitation and redissolution, a cross-linked sodium hyaluronate gel with rearranged structure is obtained. This method utilizes the non-Newtonian fluid characteristics of sodium hyaluronate, and only by controlling the flow rate of the laminar flow device, it can guide the rearrangement of the molecular structure of sodium hyaluronate during the crosslinking process, so that it maintains a linear tertiary structure. The method does not involve granulation and crushing procedures, effectively protects the integrity of the molecular structure of the cross-linked gel, and improves the anti-degradation ability of the gel. At the same time, the gel presents a particle-free linear structure, has good viscoelasticity and cohesion, and is not easy to collapse in the body after implantation, which improves the injectability and overall filling effect.

Description

technical field [0001] The invention relates to the technical field of medical biomaterials, in particular to a method for guiding the structural rearrangement of cross-linked sodium hyaluronate gel. Background technique [0002] Sodium hyaluronate is a natural polymer polysaccharide with good physical and chemical properties and biocompatibility. It is widely used in soft tissue filling and is favored in the field of medical cosmetology. Since uncrosslinked sodium hyaluronate is easily degraded rapidly by hyaluronidase in the body and has a short retention time, cross-linking agents are usually used to cross-link sodium hyaluronate to prolong its retention time in vivo. [0003] Among the existing cross-linked sodium hyaluronate fillers, a class of fillers has a particle-free smooth structure and good cohesion. Compared with common granular hyaluronic acid gels, this type of filler has a Not easy to disperse in vivo, has good face lift and resistance to deformation (J COSM...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C08J3/24C08L5/08
CPCC08J3/24C08J2305/08
Inventor 魏长征王晓彤蒋丽霞
Owner SHANGHAI QISHENG BIOLOGICAL PREPARATION CO LTD