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Preparation method of heterogeneous cross-linked sodium hyaluronate gel

A technology of sodium hyaluronate and gel, applied in the field of biomedical materials, can solve the problems of difficult control of the final concentration of sodium hyaluronate, low removal efficiency of residual test machines, adverse effects of gel properties, etc., so as to avoid adverse effects. , good viscoelasticity, high cross-linking efficiency

Pending Publication Date: 2021-12-31
北京思尔根生物科技有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

The above-mentioned method has the disadvantages that the dialysis or precipitation process takes a long time, the removal efficiency of the residual test machine is low, and the cross-linked sodium hyaluronate gel swells during dialysis so that the final concentration of sodium hyaluronate is difficult to control; the process of crushing at the same time Requires special equipment, physical extrusion during crushing also adversely affects gel properties

Method used

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  • Preparation method of heterogeneous cross-linked sodium hyaluronate gel
  • Preparation method of heterogeneous cross-linked sodium hyaluronate gel
  • Preparation method of heterogeneous cross-linked sodium hyaluronate gel

Examples

Experimental program
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Effect test

Embodiment 1

[0028] Mix 16ml of methanol and 4ml of water to obtain an alcohol-water solution with a methanol volume fraction of 80%, take 10ml of the alcohol-water solution, add 1g of sodium hyaluronate with a molecular weight of 1.3 million, and stir magnetically to form a suspension; Add 0.2g 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC), keep stirring, and react at 4°C for 90min; filter the reaction product with a Buchner funnel, and use 50ml Wash with ethanol for 3 times, collect the powder, and dry it in a blast drying oven at 40°C; disperse the dried powder in 50ml of sodium chloride solution with a pH of 6.0 and an osmotic pressure of 250mOsm / L to obtain a heterogeneous cross Sodium hyaluronate gel.

Embodiment 2

[0030] Mix 99ml of ethanol and 1ml of water to obtain an alcohol-water solution with a volume fraction of 99% ethanol, take 50ml of the alcohol-water solution, add 1g of sodium hyaluronate with a molecular weight of 2 million, and stir magnetically to form a suspension; Add 0.2g EDC, keep stirring, and react at 35°C for 60min; filter the reaction product with Buchner funnel, wash with 50ml ethanol for 3 times, collect the powder, and put it in a vacuum drying oven at 35°C to -0.08Mpa to dry; The vacuum-dried powder is dispersed in 50 ml of a solution containing disodium hydrogen phosphate and sodium dihydrogen phosphate with a pH of 8.0 and an osmotic pressure of 320 mOsm / L to obtain a heterogeneous cross-linked sodium hyaluronate gel, in which disodium hydrogen phosphate : The weight-number ratio of sodium dihydrogen phosphate is 1:0.1.

Embodiment 3

[0032] Mix 18ml of isopropanol and 2ml of water to obtain an alcohol-water solution containing isopropanol with a volume fraction of 90%, take 10ml of the alcohol-water solution, add 1g of sodium hyaluronate with a molecular weight of 500,000, and stir magnetically to form a suspension; Add 0.01g EDC to the suspension, keep stirring, and react at 25°C for 90min; filter the reaction product with Buchner funnel, wash with 50ml ethanol for 3 times, collect the powder, and put it in a vacuum drying oven at 40°C to -0.08Mpa for drying ; Disperse the vacuum-dried powder in 50ml of pH 7.2, osmotic pressure of 300mOsm / L containing disodium hydrogen phosphate and sodium dihydrogen phosphate solution to obtain heterogeneous cross-linked sodium hyaluronate gel, wherein hydrogen phosphate The weight ratio of disodium: sodium dihydrogen phosphate is 1:0.2.

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Abstract

The invention relates to a preparation method and application of heterogeneous cross-linked sodium hyaluronate gel. The preparation method comprises the following main preparation steps: dispersing sodium hyaluronate powder into an alcohol-water solution with a certain proportion, adding a catalyst, and catalyzing the sodium hyaluronate in a heterogeneous form to carry out self-crosslinking; after crosslinking, filtering and washing to remove redundant catalyst, and drying; and finally, redissolving in an aqueous solution to obtain the cross-linked sodium hyaluronate gel. The preparation method is high in cross-linking efficiency, can simply and efficiently remove the excess catalyst, can accurately control the concentration of sodium hyaluronate in the final gel, and omits the process of crushing and granulating. The prepared cross-linked sodium hyaluronate gel has good viscoelasticity and low catalyst residual quantity, and can be applied to soft tissue injection filling.

Description

technical field [0001] The invention relates to the technical field of biomedical materials, in particular to a preparation method of heterogeneous cross-linked sodium hyaluronate gel. Background technique [0002] Sodium hyaluronate is a naturally occurring glycosaminoglycan composed of repeating links of disaccharide units composed of D-glucuronic acid N-acetyl-D-glucosamine. Sodium hyaluronate has good physical and chemical properties and biocompatibility, and is widely used in ophthalmic surgery, wound repair, joint lubrication and soft tissue filling, etc. Non-cross-linked sodium hyaluronate is degraded by hyaluronidase and free radicals in the body, and has a short retention time. It usually prolongs its degradation time by cross-linking, and at the same time endows it with better mechanical properties. [0003] In terms of soft tissue filling, the current cross-linking method of sodium hyaluronate is usually to dissolve sodium hyaluronate in water to make an aqueous ...

Claims

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Application Information

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IPC IPC(8): C08J3/03C08J3/24C08L5/08
CPCC08J3/03C08J3/24C08J2305/08
Inventor 金雪坤张兰英顾建军
Owner 北京思尔根生物科技有限公司
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