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Method for guiding rearrangement of cross-linked sodium hyaluronate gel structure

A technology for cross-linking hyaluronic acid and sodium hyaluronate, which is applied in the field of medical biomaterials to achieve the effects of protecting the integrity of molecular structure, improving filling effect, good viscoelasticity and cohesion

Active Publication Date: 2020-06-05
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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  • Method for guiding rearrangement of cross-linked sodium hyaluronate gel structure
  • Method for guiding rearrangement of cross-linked sodium hyaluronate gel structure

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0024] Weigh 1g of dry sodium hyaluronate powder with a molecular weight of 1.3 million Da, and dissolve it in a 2% sodium hydroxide solution to prepare a sodium hyaluronate solution with a concentration of 2.4% (m / m). Take 150 μl of divinyl sulfone and dissolve it in 2% sodium hydroxide solution to prepare a crosslinker solution with a concentration of 1.8% (v / v). Inject the prepared sodium hyaluronate solution and the cross-linking agent solution into the microchannels A and B respectively, and adjust the flow rates of the two to 60 m / min and 10 m / min, respectively. After the solutions in the two channels enter the mixing channel, continue to flow at a flow rate of 60 m / min for 15 minutes, and the channel temperature is 40°C. Then, the preliminarily cross-linked sodium hyaluronate was drained into the cross-linking pool, heated in a water bath at 40°C, and mechanically stirred at 100 rpm for 2 hours. After the reaction is over, slowly add 95% ethanol solution until a white p...

Embodiment 2

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

[0028] The gel prepared above was freeze-dried, and after quenching with liquid nitrogen, the cross section of the gel was observed through a scanning electron microscope. Such as figure 2 As shown, the gel exhibits an isotropic porous structure.

[0029] Compared with Example 1, in...

Embodiment 3

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

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Abstract

The invention relates to a method for guiding rearrangement of a cross-linked sodium hyaluronate gel structure. The method comprises the following steps: respectively injecting sodium hyaluronate anda cross-linking agent solution into different micro-channels, controlling the flow velocities of the sodium hyaluronate and the cross-linking agent solution to enter a mixing channel, continuously flowing to generate a primary cross-linking reaction, then guiding a product into a cross-linking pool, continuously cross-linking to an end point, alkalizing, precipitating and re-dissolving to obtain the cross-linked sodium hyaluronate gel with a rearranged structure. According to the method, the non-Newtonian fluid characteristic of the sodium hyaluronate is utilized, molecular structure rearrangement of the sodium hyaluronate in the cross-linking process can be guided only by controlling the flow speed of a laminar flow device, and a linear three-level structure of the sodium hyaluronate is kept. The method does not involve granulation and crushing processes, so that the molecular structure integrity of the cross-linked gel is effectively protected, and the degradation resistance of the gel is improved. Meanwhile, the gel is of a particle-free linear structure, has good viscoelasticity and cohesiveness and is not prone to collapsing in vivo after being implanted, and the injectabilityand the overall filling effect are improved.

Description

Technical field [0001] The invention relates to the technical field of medical biomaterials, in particular to a method for guiding the rearrangement of the cross-linked sodium hyaluronate gel structure. 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 beauty. Since the uncrosslinked sodium hyaluronate is easily degraded rapidly in the body by the enzymatic hydrolysis of hyaluronidase, and the retention time is short, the crosslinking agent is usually used to crosslink the sodium hyaluronate to extend its retention time in the body. [0003] Among the existing cross-linked sodium hyaluronate fillers, one type of filler has a particle-free smooth structure and good cohesion. Compared with the common granular hyaluronic acid gel, this type of filler has It is not easy to disperse in the body, and has good ...

Claims

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Application Information

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Patent Type & Authority Applications(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