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A kind of preparation method of hyaluronic acid bioadhesive

A bioadhesive, hyaluronic acid technology, applied in surgical adhesives, surgery, medical science, etc., can solve the problems of poor wound healing, body tissue burns, poor tissue compatibility, etc., to achieve increased grafting rate, The effect of good biocompatibility and low cost

Inactive Publication Date: 2019-02-19
济南科乐医药有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, these adhesives still have various deficiencies
Although cyanoacrylate adhesives can be cured rapidly at room temperature, the heat generated by the polymerization reaction will cause a certain degree of burns to the body tissues during its use, and the poor tissue compatibility will cause poor wound healing effects; Although fibrin-based adhesives have good biocompatibility and degradability, there may be a potential risk of viral infection due to the source of allogeneic human or animal serum, and the safety of its clinical use has attracted widespread attention

Method used

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Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0023] A preparation method of hyaluronic acid bioadhesive, the preparation method is carried out according to the following steps:

[0024] a. Preparation of Paste Amorphous Hyaluronic Acid

[0025] Put hyaluronic acid and aprotic solvent in deionized water, the mass volume ratio of hyaluronic acid and deionized water is 1:10-200, the volume ratio of aprotic solvent and deionized water is 1:10-50, stir at room temperature For 1 to 24 hours, dry the solution formed by hyaluronic acid, aprotic solvent, and deionized water at a temperature of -10 to -50°C and a pressure of 50 to 200 Pa for 24 to 72 hours to obtain a paste-like amorphous transparent Glycolic acid, the aprotic solvent is a kind of in dimethylformamide or dimethylacetamide or dimethyl sulfoxide.

[0026] Hyaluronic acid is a linear polymer polysaccharide composed of D-glucuronic acid and N-acetyl-D-glucosamine as disaccharide units, which has good biocompatibility and biodegradability. As one of the main componen...

Embodiment 1

[0040] Weigh 5g of hyaluronic acid, add it to 50mL of deionized water, add 5mL of dimethylformamide, stir at room temperature for 1 hour, place the solution at -10°C and a pressure of 50Pa, and dry it for 24 hours to obtain a paste without Styling Hyaluronic Acid. Weigh 4g of pasty amorphous hyaluronic acid and 0.41g of maleic anhydride into 20mL of dimethylformamide, stir well at room temperature, and react at 25°C for 12 hours. After the reaction, add 1mol / L NaHCO 3 Solution, adjust the pH of the mixed solution to 7-8, dialyze the mixed solution, the dialysis time is 2 days, and freeze-dry the dialysate for 24 hours at a temperature of -50 ° C and a pressure of 1 Pa to obtain a molar substitution of 0.3 maleylated hyaluronic acid.

[0041] Weigh 1 g of maleylated hyaluronic acid, 0.05 g of 2-hydroxy-2-methyl-1-p-hydroxyethyl ether phenylacetone, and add to 98.95 g of Na with a pH of 7.0 2 HPO 4 -NaH 2 PO 4 In the buffer solution, mix uniformly at room temperature to obt...

Embodiment 2

[0043] Weigh 5g of hyaluronic acid, add it to 1000mL of deionized water, add 20mL of dimethylacetamide, stir at room temperature for 24 hours, place the solution at -50°C and a pressure of 200Pa, and dry for 72 hours to obtain a paste without Styling Hyaluronic Acid. Weigh 4g of pasty amorphous hyaluronic acid and 82.79g of maleic anhydride into 800mL of dimethylacetamide, stir well at room temperature, and react at 80°C for 48 hours. After the reaction, add 1mol / L of NaHCO 3 Solution, adjust the pH of the mixed solution to 7-8, dialyze the mixed solution, the dialysis time is 2 days, and freeze-dry the dialysate for 72 hours at a temperature of -50°C and a pressure of 20Pa to obtain a molar substitution of 0.8 maleylated hyaluronic acid.

[0044] Weigh 4 g of maleylated hyaluronic acid and 0.05 g of 1-hydroxycyclohexyl phenyl ketone, and add to 45.95 g of K with a pH of 7.4 2 HPO 4 -KH 2 PO 4 In the buffer solution, mix uniformly at room temperature to obtain a hyaluroni...

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Abstract

The invention relates to a preparation method of a biological adhesive, in particular to a preparation method of a hyaluronic acid biological adhesive, and belongs to the technical field of preparation of a biological material. The preparation method comprises the following steps: grafting an alkenyl group on an amorphous hyaluronic acid molecular chain according to a freeze-drying method, and performing dissolving and mixing so as to obtain the biological adhesive. According to the preparation method disclosed by the invention, a freeze-drying technology is adopted under mixed solvent environment, so that the crystal system structure of hyaluronic acid is greatly destroyed, hyaluronic acid molecules adopting an amorphous structure are formed, the grafting rate of the hyaluronic acid is greatly increased, and the problems that due to a low grafting rate, the ultra-violet curing speed is low and the formed gel is poor in intensity are completely solved. The biological adhesive prepared by the method disclosed by the invention can rapidly form gel under the irradiation of ultraviolet rays, and the gel is safe and good in biocompatibility, and can be completely degraded and absorbed. The preparation method disclosed by the invention is simple, the cost is low, and industrialized production is easy to realize.

Description

technical field [0001] The invention relates to a method for preparing a bioadhesive, in particular to a method for preparing a hyaluronic acid bioadhesive, and belongs to the technical field of biomaterial preparation. Background technique [0002] Bioadhesive is a biomedical material used to prevent tissue adhesion, stop bleeding, and prevent air and body fluid leakage during surgery. Effectively reduce the effect of scars. [0003] At present, cyanoacrylate adhesives, fibrin adhesives, etc. are widely used clinically. The Chinese patent publication number is CN104958781A, the publication date is October 7, 2015, and the title of the invention is "a chemical medical adhesive composition and its preparation method" which discloses the preparation method of cyanoacrylate adhesive; Chinese patent The publication number is CN101352581A, the publication date is January 28, 2009, and the title of the invention is "Adhesive for Articular Cartilage Repair Graft Fixation and Appl...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61L24/08A61L24/00C08B37/08
CPCA61L24/0031A61L24/0042A61L24/08C08B37/0072C08L5/08
Inventor 周应山董齐殷先泽杨红军柏自奎顾绍金陶咏真徐卫林
Owner 济南科乐医药有限公司
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