CN114887110B - Hemostatic material capable of quickly stopping bleeding and preparation method thereof - Google Patents

Hemostatic material capable of quickly stopping bleeding and preparation method thereof Download PDF

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CN114887110B
CN114887110B CN202210416612.3A CN202210416612A CN114887110B CN 114887110 B CN114887110 B CN 114887110B CN 202210416612 A CN202210416612 A CN 202210416612A CN 114887110 B CN114887110 B CN 114887110B
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chitosan
hemostatic
hydrogel
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CN114887110A (en
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臧剑锋
杨月莹
凌青
杨甲申
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Huazhong University of Science and Technology
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    • A—HUMAN NECESSITIES
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    • A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
    • A61L24/04—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials
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    • A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
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    • A61L24/0031—Hydrogels or hydrocolloids
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    • A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
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    • A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
    • A61L24/04—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials
    • A61L24/10—Polypeptides; Proteins
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    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
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    • C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
    • C08B37/0006—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid
    • C08B37/0024—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid beta-D-Glucans; (beta-1,3)-D-Glucans, e.g. paramylon, coriolan, sclerotan, pachyman, callose, scleroglucan, schizophyllan, laminaran, lentinan or curdlan; (beta-1,6)-D-Glucans, e.g. pustulan; (beta-1,4)-D-Glucans; (beta-1,3)(beta-1,4)-D-Glucans, e.g. lichenan; Derivatives thereof
    • C08B37/0027—2-Acetamido-2-deoxy-beta-glucans; Derivatives thereof
    • C08B37/003—Chitin, i.e. 2-acetamido-2-deoxy-(beta-1,4)-D-glucan or N-acetyl-beta-1,4-D-glucosamine; Chitosan, i.e. deacetylated product of chitin or (beta-1,4)-D-glucosamine; Derivatives thereof
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    • C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
    • C08B37/006—Heteroglycans, i.e. polysaccharides having more than one sugar residue in the main chain in either alternating or less regular sequence; Gellans; Succinoglycans; Arabinogalactans; Tragacanth or gum tragacanth or traganth from Astragalus; Gum Karaya from Sterculia urens; Gum Ghatti from Anogeissus latifolia; Derivatives thereof
    • C08B37/0063—Glycosaminoglycans or mucopolysaccharides, e.g. keratan sulfate; Derivatives thereof, e.g. fucoidan
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    • C08B37/0084—Guluromannuronans, e.g. alginic acid, i.e. D-mannuronic acid and D-guluronic acid units linked with alternating alpha- and beta-1,4-glycosidic bonds; Derivatives thereof, e.g. alginates
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    • C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
    • C08B37/006—Heteroglycans, i.e. polysaccharides having more than one sugar residue in the main chain in either alternating or less regular sequence; Gellans; Succinoglycans; Arabinogalactans; Tragacanth or gum tragacanth or traganth from Astragalus; Gum Karaya from Sterculia urens; Gum Ghatti from Anogeissus latifolia; Derivatives thereof
    • C08B37/0087—Glucomannans or galactomannans; Tara or tara gum, i.e. D-mannose and D-galactose units, e.g. from Cesalpinia spinosa; Tamarind gum, i.e. D-galactose, D-glucose and D-xylose units, e.g. from Tamarindus indica; Gum Arabic, i.e. L-arabinose, L-rhamnose, D-galactose and D-glucuronic acid units, e.g. from Acacia Senegal or Acacia Seyal; Derivatives thereof
    • C08B37/0096—Guar, guar gum, guar flour, guaran, i.e. (beta-1,4) linked D-mannose units in the main chain branched with D-galactose units in (alpha-1,6), e.g. from Cyamopsis Tetragonolobus; Derivatives thereof
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    • A61L2400/00—Materials characterised by their function or physical properties
    • A61L2400/04—Materials for stopping bleeding
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Abstract

The invention belongs to the technical field of medical polymer materials, and discloses a hemostatic material capable of rapidly stopping bleeding and a preparation method thereof, wherein the hemostatic material comprises a hemostatic patch, a hemostatic dressing and a hemostatic sponge, wherein the hemostatic patch is a sheet-shaped and sticky material formed by mixing and injecting a first component and a second component into a mold; the first component comprises a chitosan component and a polyacrylic acid hydrogel component, wherein the polyacrylic acid hydrogel component is grafted with N-hydroxysuccinimide ester; the second component simultaneously comprises non-aldehydized polysaccharide, dialdehyde polysaccharide and cationic salt solution; the first component and the second component can be crosslinked in situ based on Schiff base reaction after being mixed to form hydrogel, and the hydrogel has the functions of hemostasis and adhesion; the hemostatic patch is sheet hydrogel, and can rapidly stop bleeding. The hemostatic material is improved in composition, and the first component and the second component which are specific in components are adopted, so that the hemostatic material can quickly stop bleeding and form strong adhesion with tissues.

Description

Hemostatic material capable of rapidly stopping bleeding and preparation method thereof
Technical Field
The invention belongs to the technical field of medical polymer materials, and particularly relates to a hemostatic material capable of rapidly stopping bleeding and a preparation method thereof.
Background
Traumatic bleeding occurs frequently in daily life, and excessive blood loss is one of the important factors leading to death in war, traffic accident and natural disaster. The hemostatic dressing is an important material for effectively avoiding death caused by blood loss, but the traditional hemostatic dressing has the limitations of poor hemostatic effect, incapability of stopping bleeding of abnormal wounds and the like. Therefore, the development of the hemostatic dressing which has an excellent hemostatic effect, certain functionality and convenient use is of great significance.
Chinese patent literature discloses a hemostatic sponge and a preparation method and application thereof, and the application publication number is CN202010520228.9. The invention relates to a hemostatic sponge and a preparation method and application thereof. The preparation raw materials of the hemostatic composite sponge comprise chitosan, sodium alginate and fucoidan sulfate, and the weight ratio of the chitosan to the sodium alginate to the fucoidan sulfate is 1 (1-6) to 1-6. The sponge has good swelling property and water absorption property, can quickly absorb blood at a wound to cause concentration of blood cells, so as to initiate a hemostasis cascade reaction, can be locally converted into a gel state after the sponge absorbs the blood, adheres to close the wound, plays a good role in hemostasis in an aortic hemorrhage model, and quickly finishes hemostasis. The product can effectively prevent death caused by heavy bleeding, and strives for precious rescue time for next medical delivery and treatment. However, the hemostatic sponge has no adhesion function with tissues, and the wound has the problem of secondary bleeding during the recovery process after the operation, which threatens the life health of the patient.
Disclosure of Invention
In view of the above defects or improvement needs in the prior art, an object of the present invention is to provide a hemostatic material capable of rapidly stopping bleeding and a preparation method thereof, wherein the composition of the hemostatic material is improved, and hemostatic powder (first component) and hemostatic glue (second component) with specific components are adopted, so that the correspondingly obtained hemostatic material (specifically, different forms such as hemostatic patches, hemostatic dressings, hemostatic sponges and the like, which can be used as medical hemostatic materials according to different hemostatic application requirements) can rapidly stop bleeding and form tough adhesion with tissues.
To achieve the above objects, according to one aspect of the present invention, there is provided a hemostatic material capable of rapidly stopping bleeding, specifically a hemostatic patch, characterized in that the hemostatic patch is a sheet-like material exhibiting adhesiveness with biological tissues formed by mixing a first component and a second component and injecting them into a mold; wherein the content of the first and second substances,
the first component simultaneously comprises a chitosan component and a polyacrylic acid hydrogel component, wherein the chitosan component is selected from chitosan, chitosan derivatives, cellulose and chitin; the main body of the polyacrylic acid hydrogel component is polyacrylic acid hydrogel, polyacrylamide hydrogel or poly N-isopropyl acrylamide hydrogel, and the polyacrylic acid hydrogel component is grafted with N-hydroxysuccinimide ester;
the second component simultaneously comprises non-aldehydized polysaccharide, dialdehyde polysaccharide and cationic salt solution;
the first component and the second component are capable of in situ cross-linking to form a hydrogel upon mixing based on a schiff base reaction; the hydrogel has hemostatic and adhesive effects, and the hemostatic patch is sheet hydrogel and can rapidly stop bleeding.
According to another aspect of the present invention, there is provided a hemostatic material capable of rapidly stopping bleeding, particularly a hemostatic dressing, characterized in that the hemostatic dressing is a material having a pre-designed shape and exhibiting adhesion to biological tissue formed by injecting a first component and a second component into a mold by mixing; wherein the content of the first and second substances,
the first component simultaneously comprises a chitosan component and a polyacrylic acid hydrogel component, wherein the chitosan component is selected from chitosan, chitosan derivatives, cellulose and chitin; the main body of the polyacrylic acid hydrogel component is polyacrylic acid hydrogel, polyacrylamide hydrogel or poly N-isopropyl acrylamide hydrogel, and the polyacrylic acid hydrogel component is grafted with N-hydroxysuccinimide ester;
the second component simultaneously comprises non-aldehydized polysaccharide, dialdehyde polysaccharide and cationic salt solution;
the first component and the second component are capable of in situ cross-linking to form a hydrogel upon mixing based on a schiff base reaction; the hydrogel has hemostatic and adhesive effects, and the hemostatic dressing is a hydrogel with a pre-designed shape and can rapidly stop bleeding.
According to another aspect of the present invention, there is provided a hemostatic material capable of rapidly stopping bleeding, specifically a hemostatic sponge, wherein the hemostatic sponge is a porous material which is formed by mixing a first component and a second component and injecting the mixture into a mold, thereby exhibiting adhesiveness with biological tissue; wherein the content of the first and second substances,
the first component comprises a chitosan component and a polyacrylic acid hydrogel component, wherein the chitosan component is selected from chitosan, chitosan derivatives, cellulose and chitin; the main body of the polyacrylic acid hydrogel component is polyacrylic acid hydrogel, polyacrylamide hydrogel or poly N-isopropyl acrylamide hydrogel, and the polyacrylic acid hydrogel component is grafted with N-hydroxysuccinimide ester;
the second component simultaneously comprises non-aldehydized polysaccharide, dialdehyde polysaccharide and cationic salt solution;
the first component and the second component are capable of in situ cross-linking to form a hydrogel upon mixing based on a schiff base reaction; the hydrogel has hemostatic and adhesive effects, and the hemostatic sponge is porous hydrogel and can rapidly stop bleeding.
As a further preferred aspect of the present invention, in the first component, the chitosan-based component is preferably selected from chitosan and chitosan derivatives; more preferably, the chitosan component is one or a mixture of chitosan, carboxymethyl chitosan and carboxyethyl chitosan;
for the second component, the non-aldehydic polysaccharide is at least one of sodium alginate, gelatin, hyaluronic acid, genipin and guar gum;
the dialdehyde polysaccharide is at least one of aldehyde-terminated sodium alginate, aldehyde-terminated gelatin, aldehyde-terminated hyaluronic acid, aldehyde-terminated genipin and aldehyde-terminated guar gum;
the cation salt solution is selected from calcium salt solution and ferrous salt solution.
As a further preferred of the present invention, the chitosan derivative is carboxyethyl chitosan;
the first component comprises the following components in percentage by mass (2-6): (10-40): (0.1-1): (0.5-1) carboxyethyl chitosan, polyacrylic acid grafted with N-hydroxysuccinimide ester, a crosslinking agent and a photoinitiator;
or comprises the following components in percentage by mass (2-6): (10-40): (0.1-1): (0.5-1) carboxyethyl chitosan, polyacrylamide grafted with N-hydroxysuccinimide ester, a cross-linking agent and a photoinitiator;
or comprises the following components in percentage by mass (2-6): (10-40): (0.1-1): (0.5-1) carboxyethyl chitosan, poly-N-isopropylacrylamide grafted with N-hydroxysuccinimide ester, a crosslinking agent and a photoinitiator;
preferably, the cross-linking agent is methacrylic anhydrified gelatin, and the photoinitiator is alpha-ketoglutaric acid;
the mass ratio of non-aldehydized polysaccharide, dialdehyde polysaccharide and cationic salt in the second component is (1-4): (2-20): (0.02-0.08).
As a further preferred aspect of the present invention, the chitosan derivative is carboxyethyl chitosan, which is synthesized by the following method:
under the condition of 20-50 ℃, dissolving 1-10 wt% of chitosan powder in acrylic acid aqueous solution to obtain mixed solution, wherein the mass percentage concentration of chitosan in the mixed solution is 1-10 wt%; then reacting the mixed solution at 50 ℃ for 1-3 days, then adjusting the pH value to 10-12, and dialyzing in deionized water to obtain a carboxyethyl chitosan solution; and then drying the carboxyethyl chitosan solution, and grinding to obtain the carboxyethyl chitosan powder.
As a further preferable mode of the invention, the aldehyde-terminated sodium alginate is synthesized by the following method: adding sodium periodate into 1-4wt% sodium alginate solution at 10-25 deg.c, and light shielding reaction for 12-24 hr; adding polyethylene glycol to react for 0.5-2h, dialyzing in deionized water, drying, and grinding to obtain aldehyde-terminated sodium alginate powder;
the aldehyde-terminated gelatin is synthesized by the following method: adding sodium periodate into 1-4wt% gelatin solution at 10-25 deg.c, and light shielding reaction for 12-24 hr; adding polyethylene glycol to react for 0.5-2h, dialyzing in deionized water, drying, and grinding to obtain aldehyde group-terminated gelatin powder;
the aldehyde-terminated hyaluronic acid is synthesized by the following method: adding sodium periodate into 1-4wt% hyaluronic acid solution at 10-25 deg.C, and reacting for 12-24h in dark; adding polyethylene glycol to react for 0.5-2h, dialyzing in deionized water, drying, and grinding to obtain aldehyde-terminated hyaluronic acid powder;
the aldehyde-terminated genipin is synthesized by the following method: adding sodium periodate into 1-4wt% genipin solution at 10-25 deg.C, and reacting for 12-24h in dark; adding polyethylene glycol to react for 0.5-2h, dialyzing in deionized water, drying, and grinding to obtain aldehyde-terminated genipin powder;
the aldehyde-terminated guar gum is synthesized by the following method: adding sodium periodate into 1-4wt% guar gum solution at 10-25 deg.C, and reacting for 12-24h in dark; and then adding polyethylene glycol to react for 0.5-2h, dialyzing in deionized water, drying, and grinding to obtain the aldehyde-terminated guar gum powder.
According to another aspect of the present invention, there is provided a method for preparing the hemostatic material capable of rapidly stopping bleeding, which comprises preparing a first component, preparing a second component and preparing a patch, wherein:
the first component is prepared by dissolving chitosan components in deionized water at 20-50 ℃, and adding a monomer, a cross-linking agent, N-acryloyloxy succinimide and a photoinitiator to obtain a first component solution; wherein the monomer is an acrylic acid monomer, an acrylamide monomer or an N-isopropyl acrylamide monomer;
the second component is prepared by mixing non-aldehydized polysaccharide and dialdehyde polysaccharide in metal cation salt solution at 10-25 ℃ to obtain second component solution; wherein the synthesis process of the dialdehyde polysaccharide comprises the following steps: dissolving non-aldehydized polysaccharide in deionized water at 10-25 deg.c to obtain 1-4wt% non-aldehydized polysaccharide solution, adding sodium periodate into the non-aldehydized polysaccharide solution for light-shielding reaction for 12-24 hr, and adding polyglycol for reaction for 0.5-2 hr; then, dialyzing the reaction system in deionized water, drying, and grinding to obtain dialdehyde polysaccharide;
preparation of the patch: mixing the first component solution and the second component solution to obtain a preset solution; then, injecting the preset solution into a patch die, carrying out ultraviolet polymerization and drying to obtain the hemostatic patch; preferably, the preset solution is injected into a glass patch mold with a molding area depth of 500 μm, polymerized for 10-60min under 365nm ultraviolet light, opened, and dried in nitrogen for 24h.
According to a further aspect of the present invention, there is provided a method for preparing the hemostatic material capable of rapidly stopping bleeding, which comprises preparing a first component, preparing a second component and preparing a dressing, wherein:
the first component is prepared by dissolving chitosan components in deionized water at 20-50 ℃, and adding a monomer, a cross-linking agent, N-acryloyloxy succinimide and a photoinitiator to obtain a first component solution; wherein the monomer is an acrylic acid monomer, an acrylamide monomer or an N-isopropyl acrylamide monomer;
the second component is prepared by mixing non-aldehydized polysaccharide and dialdehyde polysaccharide in metal cation salt solution at 10-25 ℃ to obtain second component solution; wherein the synthesis process of the dialdehyde polysaccharide comprises the following steps: dissolving non-aldehydized polysaccharide in deionized water at 10-25 deg.c to obtain 1-4wt% non-aldehydized polysaccharide solution, adding sodium periodate into the non-aldehydized polysaccharide solution for light-shielding reaction for 12-24 hr, and adding polyglycol for reaction for 0.5-2 hr; then, dialyzing the reaction system in deionized water, drying, and grinding to obtain dialdehyde polysaccharide;
preparation of the dressing: mixing the first component solution and the second component solution to obtain a preset solution; then, injecting the preset solution into a dressing mold, and carrying out ultraviolet polymerization to obtain the hemostatic dressing; preferably, the ultraviolet polymerization is specifically polymerization under 365nm ultraviolet light for 10-60min.
According to a final aspect of the present invention, there is provided a method for preparing the hemostatic material capable of rapidly stopping bleeding, which comprises preparing a first component, preparing a second component and preparing a sponge, wherein:
the first component is prepared by dissolving chitosan components in deionized water at 20-50 ℃, and adding a monomer, a cross-linking agent, N-acryloyloxy succinimide and a photoinitiator to obtain a first component solution; wherein the monomer is an acrylic acid monomer, an acrylamide monomer or an N-isopropyl acrylamide monomer;
the second component is prepared by mixing non-aldehydized polysaccharide and dialdehyde polysaccharide in metal cation salt solution at 10-25 ℃ to obtain second component solution; wherein the synthesis process of the dialdehyde polysaccharide comprises the following steps: dissolving non-aldehydized polysaccharide in deionized water at 10-25 deg.c to obtain 1-4wt% non-aldehydized polysaccharide solution, adding sodium periodate into the non-aldehydized polysaccharide solution for light-shielding reaction for 12-24 hr, and adding polyglycol for reaction for 0.5-2 hr; then, dialyzing the reaction system in deionized water, drying, and grinding to obtain dialdehyde polysaccharide;
preparing the sponge: mixing the first component solution and the second component solution to obtain a preset solution; then, injecting the preset solution into a mold, performing ultraviolet polymerization, then putting the gelled sample into a PBS (phosphate buffer solution) solution for swelling treatment, and after complete swelling, performing freeze drying to obtain the hemostatic sponge; preferably, the ultraviolet polymerization is specifically polymerization under 365nm ultraviolet light for 10-60min; the freeze drying is carried out by pre-freezing at-80 ℃ and then freeze drying at-40 ℃.
Compared with the prior art, the technical scheme of the invention has the advantages that the first component and the second component which are specially composed are adopted, and the hydrogel formed by in-situ crosslinking through Schiff base reaction has the characteristics of quick hemostasis, good adhesion with biological tissues and the like. The composition comprises a component A (namely, a first component) and a component B (namely, a second component), wherein the component A is a hemostatic component consisting of chitosan derivatives and polyacrylic acid hydrogel with high viscosity, the component B is hemostatic glue consisting of polysaccharide, dialdehyde polysaccharide and cationic salt solution, and the component A and the component B are mutually crosslinked in situ to form hydrogel based on Schiff base reaction; the quick hemostatic hydrogel can beSo as to absorb liquid components in blood, improve the concentration of blood coagulation factors, cause the aggregation of red blood cells, improve the activity of platelets and further quickly stop bleeding. And, on the other hand, can rapidly form temporary adhesion (Ca) with tissues by the aldehyde group in the B component 2+ Ions, fe 2+ Ions of the metal cations can be connected with polysaccharide through coordination bonds to generate stable chelate), then N-hydroxysuccinimide ester on the polyacrylic acid hydrogel molecular chain can perform ester exchange reaction with biological tissues to form strong adhesion and close wound positions, and the chitosan derivative in the component A and the dialdehyde polysaccharide in the component B can form dynamic Schiff base, so that the hemostatic bag has the advantages of rapid hemostasis, rapid adhesion and strong adhesion.
And the component A is a hemostatic hydrogel network consisting of a chitosan derivative and polyacrylic hydrogel with high viscosity, can absorb liquid components in blood, improve the concentration of blood coagulation factors, cause erythrocyte aggregation, improve platelet activity and further realize rapid hemostasis, and hydroxyl succinimide ester is preferably arranged on the molecular chain of the polyacrylic hydrogel and can perform ester exchange reaction with biological tissues to form strong and tough adhesion to seal wound parts, so that rapid hemostasis is realized and strong and tough adhesion with the tissues is formed.
Specifically, the present invention can achieve the following advantageous effects:
1. the hemostatic material capable of rapidly stopping bleeding provided by the invention integrates excellent functions and biological activities of all raw materials, can help wounds to rapidly stop bleeding, can form strong adhesion with tissues, and provides an ideal microenvironment for growth, proliferation and differentiation of cells.
2. The hemostatic material (such as hemostatic double-sided patch, hemostatic dressing and hemostatic sponge) capable of rapidly stopping bleeding can be used together with instruments in minimally invasive surgery, is simple to operate, and can be used for clinical surgical hemostasis and emergency treatment.
In conclusion, the hemostatic material of the present invention, whether a hemostatic patch, a hemostatic dressing, or a hemostatic sponge, is adhesive when attached to a biological tissue, and is a hemostatic material that can rapidly stop bleeding and form a strong adhesion with the tissue, and not only can rapidly stop bleeding, but also can form a strong adhesion with the contacted tissue, thereby further fundamentally preventing the wound from bleeding again. The component A can absorb liquid components in blood, improve the concentration of blood coagulation factors, cause erythrocyte aggregation, improve the activity of platelets and further quickly stop bleeding, the aldehyde group on the component B can form quick temporary adhesion with tissues to seal wounds, and the hydroxyl succinimide ester is arranged on the polyacrylic acid hydrogel molecular chain on the component A and can perform ester exchange reaction with biological tissues to form a tough adhesion to seal wound parts.
Drawings
FIG. 1 is a functional schematic of a hemostatic material of the invention that rapidly stanchs and forms a tenacious adhesion with tissue.
Fig. 2 is an adhesion mechanism of a hemostatic material of the invention that rapidly stanchs and forms a strong adhesion to tissue.
FIG. 3 is FTIR results for a hemostatic material of the present invention that rapidly stanchs and forms a strong adhesion to tissue.
FIG. 4 is a graph showing the hemostatic and adhesive effects of the hemostatic patch obtained in example 1 of the present invention on animal tissues (rat wounds with liver bleeding); the figure is a picture after 1 hour of adhesion.
FIG. 5 is a graph showing the hemostatic and adhesive effects of the hemostatic material obtained in example 2 of the present invention on animal tissues (a wound of a rat with a portion of the kidney cut bleeding); the figure is a picture after 1 hour of adhesion.
FIG. 6 is a graph showing the hemostatic and adhesive effects of the hemostatic material obtained in example 3 of the present invention on animal tissues (a wound of a rat with a portion of the kidney cut bleeding); the figure is a picture after 1 hour of adhesion.
FIG. 7 is a graph showing the hemostatic and adhesive effects of the hemostatic dressing obtained in example 4 of the present invention on animal tissues (bleeding liver in a wound of a rat); the left image is a photograph after 1 hour of adhesion, and the right image is a photograph after 14 days.
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is described in further detail below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention. In addition, the technical features involved in the embodiments of the present invention described below may be combined with each other as long as they do not conflict with each other.
In general, the hemostatic material for rapidly stopping bleeding in the present invention is a portion (denoted as a first component) capable of adhering to and coagulating blood of tissue, which is composed of chitosan and its derivatives, and polyacrylic hydrogel having high viscosity, and a portion (denoted as a second component) capable of crosslinking with chitosan and its derivatives, which is composed of polysaccharide, dialdehyde polysaccharide, and cationic salt solution.
The chitosan and its derivatives may be one or two of chitosan, carboxymethyl chitosan and carboxyethyl chitosan.
The polyacrylic acid hydrogel with high viscosity is polyacrylic acid polymer with hydroxy succinimide ester on the molecular chain of the polyacrylic acid hydrogel.
The polysaccharide and dialdehyde polysaccharide in the hemostatic glue consisting of polysaccharide, dialdehyde polysaccharide and cationic salt solution can be sodium alginate and aldehyde-terminated sodium alginate. The aldehyde-group-blocked sodium alginate is also called oxidized sodium alginate.
The first component may consist, for example, of 2 to 4% carboxyethyl chitosan, 10 to 30% acrylic acid, 0.1 to 0.5% methacrylic anhydrified gelatin, 0.5 to 2% N-acryloxysuccinimide, 0.5 to 1% of a photoinitiator.
In addition, in the synthesis, the synthesis method of the carboxyethyl chitosan can be, for example: dissolving a certain amount of chitosan powder in an acrylic acid aqueous solution at normal temperature, reacting for 3 days at 50 ℃, adding a 1N sodium hydroxide solution to adjust the pH to 11, dialyzing for 3 days in deionized water, freeze-drying at-40 ℃, and then freeze-grinding to obtain carboxyethyl chitosan powder.
The synthesis method of oxidized sodium alginate can be, for example: dissolving a certain amount of sodium alginate powder in 100ml of deionized water at normal temperature, standing overnight, adding a corresponding amount of sodium periodate, and reacting for 24 hours in a dark place. Adding 1.5ml of polyethylene glycol to react for 1h, dialyzing in deionized water for 3 days, freeze-drying at-40 ℃, and then freeze-grinding to obtain the oxidized sodium alginate.
The three hemostatic materials, namely the hemostatic patch, the hemostatic dressing and the hemostatic sponge, can be synthesized by the following steps (taking cationic salt as calcium chloride as an example):
at normal temperature, dissolving carboxyethyl chitosan in deionized water, and adding acrylic acid, methacrylic acid anhydrified gelatin, N-acryloyloxy succinimide and alpha-ketoglutaric acid to obtain a solution A. Oxidized sodium alginate was dissolved in deionized water. Sodium alginate was dissolved in deionized water. Calcium chloride was dissolved in deionized water. Mixing an oxidized sodium alginate solution, a sodium alginate solution and a calcium chloride solution according to the mass ratio of 25.
At normal temperature, dissolving carboxyethyl chitosan in deionized water, and adding acrylic acid, methacrylic acid anhydrified gelatin, N-acryloyloxy succinimide and alpha-ketoglutaric acid to obtain a solution A. Oxidized sodium alginate was dissolved in deionized water. Sodium alginate was dissolved in deionized water. Calcium chloride was dissolved in deionized water. Mixing an oxidized sodium alginate solution, a sodium alginate solution and a calcium chloride solution according to the mass ratio of 25.
At normal temperature, dissolving carboxyethyl chitosan in deionized water, and adding acrylic acid, methacrylic acid anhydrified gelatin, N-acryloyloxy succinimide and alpha-ketoglutaric acid to obtain a solution A. Oxidized sodium alginate was dissolved in deionized water. Sodium alginate was dissolved in deionized water. Calcium chloride was dissolved in deionized water. Mixing an oxidized sodium alginate solution, a sodium alginate solution and a calcium chloride solution according to the mass ratio of 25 to 1 to obtain a solution B, mixing the solution A and the solution B according to the mass ratio of 1 to obtain a pre-gelatinized liquid, pouring the pre-gelatinized solution into a designed glass mold, polymerizing for 10-60min under 365nm ultraviolet light, opening the mold, putting the gelatinized sample into a PBS solution for swelling, putting the sample into a temperature of-80 ℃ for pre-freezing after complete swelling, and further performing freeze drying to obtain the hemostatic sponge.
The following are specific examples:
example 1
(1) 4g of carboxyethyl chitosan was dissolved in 72g of deionized water at room temperature, and 16g of acrylic acid was added overnight.
(2) Adding 2g of methacrylic anhydrified gelatin, 4g of N-acryloyloxy succinimide and 2g of alpha-ketoglutaric acid into the solution to obtain a solution A, wherein the mass ratio of the carboxyethyl chitosan, the polyacrylic acid grafted with N-hydroxysuccinimide ester, the crosslinking agent and the photoinitiator in the solution A is 2.
(3) 4g of oxidized sodium alginate was dissolved in 96g of deionized water. 8g of sodium alginate was dissolved in 92g of deionized water. 1g of calcium chloride was dissolved in 99g of deionized water. Mixing the oxidized sodium alginate solution, the sodium alginate solution and the calcium chloride solution at a mass ratio of 25.
(4) Mixing the solution A and the solution B according to a mass ratio of 1.
Example 2
(1) 8g of carboxyethyl chitosan was dissolved in 50g of deionized water at room temperature, and 38g of acrylic acid was added overnight.
(2) Adding 1g of methacrylic anhydrified gelatin, 2g of N-acryloyloxy succinimide and 1g of alpha-ketoglutaric acid into the solution to obtain a solution A, wherein the mass ratio of the carboxyethyl chitosan, the polyacrylic acid grafted with N-hydroxysuccinimide ester, the crosslinking agent and the photoinitiator in the solution A is 8.
(3) 8g of oxidized sodium alginate was dissolved in 92g of deionized water. 4g of sodium alginate was dissolved in 96g of deionized water. 1g of calcium chloride was dissolved in 99g of deionized water. Mixing the oxidized sodium alginate solution, the sodium alginate solution and the calcium chloride solution at a mass ratio of 25.
(4) Mixing the solution A and the solution B according to a mass ratio of 1.
Example 3
(1) 12g of carboxyethyl chitosan was dissolved in 26.8g of deionized water at room temperature, and 56g of acrylic acid was added overnight.
(2) Adding 0.2g of methacrylic anhydride gelatin, 4g of N-acryloyloxy succinimide and 1g of alpha-ketoglutaric acid into the solution to obtain a solution A, wherein the mass ratio of the carboxyethyl chitosan, the polyacrylic acid grafted with N-hydroxysuccinimide ester, the crosslinking agent and the photoinitiator in the solution A is (12.2).
(3) 40g of oxidized sodium alginate was dissolved in 60g of water. 4g of sodium alginate was dissolved in 96g of water. 1g of calcium chloride was dissolved in 99g of water. Mixing an oxidized sodium alginate solution, a sodium alginate solution and a calcium chloride solution at a mass ratio of 25.
(4) And mixing the solution A and the solution B according to a mass ratio of 5.
Example 4
(1) 4g of carboxyethyl chitosan was dissolved in 72g of water at room temperature, and 16g of acrylic acid was added overnight.
(2) Adding 2g of methacrylic anhydrified gelatin, 4g of N-acryloyloxy succinimide and 2g of alpha-ketoglutaric acid into the solution to obtain a solution A, wherein the mass ratio of the carboxyethyl chitosan, the polyacrylic acid grafted with N-hydroxysuccinimide ester, the crosslinking agent and the photoinitiator in the solution A is 2.
(3) 20g of sodium alginate oxide was dissolved in 80g. 2g of sodium alginate was dissolved in 98g of water. 4g of calcium chloride are dissolved in 96g of deionized water. Mixing the oxidized sodium alginate solution, the sodium alginate solution and the calcium chloride solution in a mass ratio of 25.
(4) Mixing the solution A and the solution B according to a mass ratio of 5.
Example 5
(1) 12g of carboxyethyl chitosan was dissolved in 26.8g of deionized water at room temperature, and 56g of acrylic acid was added overnight.
(2) Adding 0.2g of methacrylic anhydride gelatin, 4g of N-acryloyloxy succinimide and 1g of alpha-ketoglutaric acid into the solution to obtain a solution A, wherein the mass ratio of the carboxyethyl chitosan, the polyacrylic acid grafted with N-hydroxysuccinimide ester, the crosslinking agent and the photoinitiator in the solution A is (12.2).
(3) 20g of oxidized sodium alginate was dissolved in 80g of deionized water. 4g of sodium alginate was dissolved in 96g of deionized water. 1g of calcium chloride was dissolved in 99g of deionized water. Mixing an oxidized sodium alginate solution, a sodium alginate solution and a calcium chloride solution at a mass ratio of 25.
(4) Mixing the solution A and the solution B according to a mass ratio of 5 to 6 to obtain a pre-gelling liquid, pouring the pre-gelling liquid into a glass mold, polymerizing for 10-60min under 365nm ultraviolet light, opening the mold, putting the gelled sample into a PBS (phosphate buffer solution) solution for swelling, after complete swelling, putting the sample into a temperature of-80 ℃ for pre-freezing, and further carrying out freeze drying to obtain the hemostatic sponge.
Example 6
(1) At room temperature, 4g of carboxyethyl chitosan was dissolved in 72g of deionized water, and 16g of acrylic acid was added overnight.
(2) Adding 2g of methacrylic anhydride gelatin, 4g of N-acryloyloxy succinimide and 2g of alpha-ketoglutaric acid into the solution to obtain a solution A, wherein the mass ratio of the carboxyethyl chitosan, the polyacrylic acid grafted with N-hydroxysuccinimide ester, the crosslinking agent and the photoinitiator in the solution A is 2.
(3) 8g of oxidized sodium alginate was dissolved in 92g of deionized water. 4g of sodium alginate was dissolved in 96g of deionized water. 1g of calcium chloride was dissolved in 99g of deionized water. Mixing the oxidized sodium alginate solution, the sodium alginate solution and the calcium chloride solution at a mass ratio of 25.
(4) Mixing the solution A and the solution B according to the mass ratio of 6.
Example 7
(1) 4g of carboxyethyl chitosan was dissolved in 72g of deionized water at room temperature, and 16g of acrylic acid was added overnight.
(2) Adding 2g of methacrylic anhydrified gelatin, 4g of N-acryloyloxy succinimide and 2g of alpha-ketoglutaric acid into the solution to obtain a solution A, wherein the mass ratio of the carboxyethyl chitosan, the polyacrylic acid grafted with N-hydroxysuccinimide ester, the crosslinking agent and the photoinitiator in the solution A is 2.
(3) 8g of oxidized sodium alginate was dissolved in 92g of deionized water. 4g of sodium alginate was dissolved in 96g of deionized water. 1g of calcium chloride was dissolved in 99g of deionized water. Mixing the oxidized sodium alginate solution, the sodium alginate solution and the calcium chloride solution at a mass ratio of 25.
(4) Mixing the solution A and the solution B according to a mass ratio of 3.
Example 8
(1) 4g of carboxyethyl chitosan was dissolved in 72g of deionized water at room temperature, and 16g of acrylic acid was added overnight.
(2) Adding 2g of methacrylic anhydride gelatin, 4g of N-acryloyloxy succinimide and 2g of alpha-ketoglutaric acid into the solution to obtain a solution A, wherein the mass ratio of the carboxyethyl chitosan, the polyacrylic acid grafted with N-hydroxysuccinimide ester, the crosslinking agent and the photoinitiator in the solution A is 2.
(3) 4g of oxidized sodium alginate was dissolved in 96g of deionized water. 8g of sodium alginate was dissolved in 92g of deionized water. 1g of ferrous chloride was dissolved in 99g of deionized water. Mixing an oxidized sodium alginate solution, a sodium alginate solution and a ferrous chloride solution in a mass ratio of 25.
(4) Mixing the solution A and the solution B according to a mass ratio of 1.
Example 9
(1) 8g of carboxyethyl chitosan was dissolved in 50g of deionized water at room temperature, and 38g of acrylic acid was added thereto overnight.
(2) Adding 1g of methacrylic anhydride gelatin, 2g of N-acryloyloxy succinimide and 1g of alpha-ketoglutaric acid into the solution to obtain a solution A, wherein the mass ratio of the carboxyethyl chitosan, the polyacrylic acid grafted with N-hydroxysuccinimide ester, the crosslinking agent and the photoinitiator in the solution A is (8).
(3) 8g of oxidized sodium alginate was dissolved in 92g of deionized water. 4g of sodium alginate was dissolved in 96g of deionized water. 1g of ferrous chloride was dissolved in 99g of deionized water. Mixing the oxidized sodium alginate solution, the sodium alginate solution and the ferrous chloride solution in a mass ratio of 25.
(4) Mixing the solution A and the solution B according to a mass ratio of 1.
Example 10
(1) 12g of carboxyethyl chitosan was dissolved in 26.8g of deionized water at room temperature, and 56g of acrylic acid was added overnight.
(2) Adding 0.2g of methacrylic anhydride gelatin, 4g of N-acryloyloxy succinimide and 1g of alpha-ketoglutaric acid into the solution to obtain a solution A, wherein the mass ratio of the carboxyethyl chitosan, the polyacrylic acid grafted with N-hydroxysuccinimide ester, the crosslinking agent and the photoinitiator in the solution A is (12.2).
(3) 40g of oxidized sodium alginate was dissolved in 60g of water. 4g of sodium alginate was dissolved in 96g of water. 1g of ferrous chloride was dissolved in 99g of water. Mixing an oxidized sodium alginate solution, a sodium alginate solution and a ferrous chloride solution in a mass ratio of 25.
(4) Mixing the solution A and the solution B according to a mass ratio of 5.
Example 11
(1) 4g of carboxyethyl chitosan was dissolved in 72g of water at room temperature, and 16g of acid was added overnight.
(2) Adding 2g of methacrylic anhydrified gelatin, 4g of N-acryloyloxy succinimide and 2g of alpha-ketoglutaric acid into the solution to obtain a solution A, wherein the mass ratio of the carboxyethyl chitosan, the polyacrylic acid grafted with N-hydroxysuccinimide ester, the crosslinking agent and the photoinitiator in the solution A is 2.
(3) 20g of sodium alginate oxide was dissolved in 80g. 2g of sodium alginate was dissolved in 98g of water. 4g of ferrous chloride was dissolved in 96g of deionized water. Mixing an oxidized sodium alginate solution, a sodium alginate solution and a ferrous chloride solution in a mass ratio of 25.
(4) Mixing the solution A and the solution B according to a mass ratio of 5.
Example 12
(1) 12g of carboxyethyl chitosan was dissolved in 26.8g of deionized water at room temperature, and 56g of acrylic acid was added thereto overnight.
(2) To the above solution were added 0.2g of methacrylic anhydrified gelatin, 4g of N-acryloyloxy succinimide, and 1g of α -ketoglutaric acid to obtain solution a, at which time the mass ratio of carboxyethyl chitosan, polyacrylic acid grafted with N-hydroxysuccinimide ester, crosslinking agent, and photoinitiator in solution a was 12.2.
(3) 20g of sodium alginate oxide was dissolved in 80g of deionized water. 4g of sodium alginate was dissolved in 96g of deionized water. 1g of ferrous chloride was dissolved in 99g of deionized water. Mixing an oxidized sodium alginate solution, a sodium alginate solution and a ferrous chloride solution in a mass ratio of 25.
(4) Mixing the solution A and the solution B according to a mass ratio of 5 to 6 to obtain a pre-gelling liquid, pouring the pre-gelling liquid into a glass mold, polymerizing for 10-60min under 365nm ultraviolet light, opening the mold, putting the gelled sample into a PBS (phosphate buffer solution) solution for swelling, after complete swelling, putting the sample into a temperature of-80 ℃ for pre-freezing, and further carrying out freeze drying to obtain the hemostatic sponge.
At room temperature, FTIR test was first performed on the hemostatic sponge obtained in example 5, and the result is shown in FIG. 3, which is 1160cm visible -1 And 1232cm -1 The N-hydroxysuccinimide ester is a characteristic peak of the N-hydroxysuccinimide ester, and can react with amino on biological tissues to form a strong and tough chemical bond so as to realize a strong and tough adhesive N-hydroxysuccinimide ester group; in addition, 1700cm can be seen -1 The characteristic peak of aldehyde group is shown, which indicates that the aldehyde group which can form Schiff base with amino exists.
The double-sided hemostatic patches obtained in examples 1, 2 and 3 were subjected to hemostasis and adhesion function tests of normal rats, the prepared hemostatic patch of example 1 was attached to the wounds of rats with liver bleeding, as shown in fig. 4, and in the experiment, effective hemostasis was observed within 10s, no blood was oozed within 1 hour, and the patch was stopped within a white circle. The hemostatic patch of example 2 was applied to the wound of a rat with a partially nephrectomized hemorrhage, as shown in fig. 5, and the effect of hemostasis was observed within 10s, no bleeding within 1 hour, and the hemostatic patch was within the white dotted circle. The hemostatic patch of example 3 was applied to the wound of a rat with a partially nephrectomized hemorrhage, as shown in fig. 6, and the effect of hemostasis was observed within 10s, no bleeding within 1 hour, and the hemostatic patch was within the white dotted circle.
The hemostatic dressing obtained in example 4 is subjected to a test of hemostasis and adhesion functions of a normal rat, the prepared hemostatic dressing of example 4 is attached to a wound of a rat with liver bleeding, as shown in fig. 7, the bleeding is effectively stopped within 10s in the experiment, the left picture shows that the hemostatic dressing has no bleeding within 1 hour, the hemostatic dressing is in a white dotted line circle, the right picture is a picture after operation for 14 days, and the hemostatic dressing is still adhered to the kidney injury and has no secondary bleeding around the kidney injury.
The hemostatic dressings obtained in examples 6 and 7 have similar hemostatic effects to those of the hemostatic dressing of example 4 in terms of their main components when applied to a bleeding wound of a biological tissue. Since the hemostatic material (including hemostatic patch, hemostatic dressing, hemostatic sponge) and the biological tissue in the present invention mainly have the first component (i.e., component a), the higher the content of component a, the stronger the adhesion between the whole hemostatic material and the biological tissue tends to be. For example, in the step (4) of each of the above embodiments, the first component solution and the second component solution are mixed to obtain the predetermined solution, and the mass ratio of the dialdehyde polysaccharide contained in the predetermined solution to the chitosan component contained in the predetermined solution can be 1/6 to 1/1, so that the hemostatic material obtained correspondingly has both good hemostatic effect and good adhesion effect with biological tissues.
Examples 8-12 have similar hemostatic effects to those of examples 1-5 above in the treatment of bleeding wounds in biological tissue, except that the cationic component of the second component is different.
The above examples are merely illustrative, and for example, calcium salts other than calcium chloride may be used, such as sulfates; the ferrous ion salt is treated in the same way; the first component can adopt other cationic high molecular polymers with amino groups, such as chitosan derivatives, cellulose and chitin, besides chitosan and carboxyethyl chitosan, and the second component can adopt other polysaccharide which can be dialdehyde, such as gelatin, hyaluronic acid, genipin, guar gum and the like, besides sodium alginate.
It will be understood by those skilled in the art that the foregoing is only an exemplary embodiment of the present invention, and is not intended to limit the invention to the particular forms disclosed, since various modifications, substitutions and improvements within the spirit and scope of the invention are possible and within the scope of the appended claims.

Claims (11)

1. A hemostatic material capable of rapidly stopping bleeding, in particular a hemostatic patch, characterized in that the hemostatic patch is a sheet-like material which is formed by mixing a first component and a second component and injecting the mixture into a mold, and which exhibits adhesiveness with respect to a biological tissue; wherein the content of the first and second substances,
the first component simultaneously comprises a chitosan component and a polyacrylic acid hydrogel component, wherein the chitosan component is selected from chitosan, chitosan derivatives, cellulose and chitin; the main body of the polyacrylic acid hydrogel component is polyacrylic acid hydrogel, polyacrylamide hydrogel or poly N-isopropyl acrylamide hydrogel, and the polyacrylic acid hydrogel component is grafted with N-hydroxysuccinimide ester;
the second component simultaneously comprises non-aldehydized polysaccharide, dialdehyde polysaccharide and cationic salt solution;
the first component and the second component are capable of in situ cross-linking to form a hydrogel upon mixing based on a schiff base reaction; the hydrogel is formed by mixing a solution of a first component and a solution of a second component to obtain a preset solution, injecting the preset solution into a patch die, and carrying out ultraviolet polymerization and drying; the hydrogel has hemostatic and adhesive effects, and the hemostatic patch is sheet hydrogel and can rapidly stop bleeding.
2. A hemostatic material capable of rapidly stopping bleeding, in particular a hemostatic sponge, is characterized in that the hemostatic sponge is a porous material which is formed by mixing a first component and a second component and injecting the mixture into a mold, so that the porous material acts on biological tissues and shows viscosity; wherein, the first and the second end of the pipe are connected with each other,
the first component simultaneously comprises a chitosan component and a polyacrylic acid hydrogel component, wherein the chitosan component is selected from chitosan, chitosan derivatives, cellulose and chitin; the main body of the polyacrylic acid hydrogel component is polyacrylic acid hydrogel, polyacrylamide hydrogel or poly N-isopropyl acrylamide hydrogel, and the polyacrylic acid hydrogel component is grafted with N-hydroxysuccinimide ester;
the second component simultaneously comprises non-aldehydized polysaccharide, dialdehyde polysaccharide and cationic salt solution;
the first component and the second component are capable of in situ cross-linking to form a hydrogel upon mixing based on a schiff base reaction; the hydrogel is prepared by mixing a solution of a first component with a solution of a second component to obtain a preset solution, injecting the preset solution into a mold, performing ultraviolet polymerization, then putting a gelatinized sample into a PBS solution for swelling treatment, and performing freeze drying after complete swelling; the hydrogel has hemostatic and adhesive effects, and the hemostatic sponge is porous hydrogel and can rapidly stop bleeding.
3. Hemostatic material according to any one of claims 1-2, wherein for the first component the chitosan-based component is selected from the group consisting of chitosan and chitosan derivatives;
for the second component, the non-aldehydized polysaccharide is at least one of sodium alginate, gelatin, hyaluronic acid, genipin and guar gum;
the dialdehyde polysaccharide is at least one of aldehyde-terminated sodium alginate, aldehyde-terminated gelatin, aldehyde-terminated hyaluronic acid, aldehyde-terminated genipin and aldehyde-terminated guar gum;
the cation salt solution is selected from calcium salt solution and ferrous salt solution.
4. Hemostatic material according to claim 3, wherein the chitosan-based component is a mixture of one or more of chitosan, carboxymethyl chitosan, carboxyethyl chitosan.
5. The hemostatic material of claim 3, wherein the chitosan derivative is carboxyethyl chitosan;
the first component comprises the following components in percentage by mass (2-6): (10-40): (0.1-1): (0.5-1) carboxyethyl chitosan, polyacrylic acid grafted with N-hydroxysuccinimide ester, a crosslinking agent and a photoinitiator;
or comprises the following components in percentage by mass (2-6): (10-40): (0.1-1): (0.5-1) carboxyethyl chitosan, polyacrylamide grafted with N-hydroxysuccinimide ester, a crosslinking agent and a photoinitiator;
or comprises the following components in percentage by mass (2-6): (10-40): (0.1-1): (0.5-1) carboxyethyl chitosan, poly-N-isopropylacrylamide grafted with N-hydroxysuccinimide ester, a crosslinking agent and a photoinitiator;
the cross-linking agent is methacrylic acid anhydrified gelatin, and the photoinitiator is alpha-ketoglutaric acid;
the mass ratio of non-aldehydized polysaccharide to dialdehyde polysaccharide to cationic salt in the second component is (1-4): (2-20): (0.02-0.08).
6. The hemostatic material of claim 3, wherein the chitosan derivative is carboxyethyl chitosan synthesized by the following method:
under the condition of 20-50 ℃, dissolving 1-10 wt% of chitosan powder in acrylic acid aqueous solution to obtain mixed solution, wherein the mass percentage concentration of chitosan in the mixed solution is 1-10 wt%; then reacting the mixed solution at 50 ℃ for 1-3 days, then adjusting the pH value to 10-12, and dialyzing in deionized water to obtain a carboxyethyl chitosan solution; and then drying the carboxyethyl chitosan solution, and grinding to obtain the carboxyethyl chitosan powder.
7. The hemostatic material of claim 3, wherein the aldehyde-terminated sodium alginate is synthesized by the following method: adding sodium periodate into 1-4wt% sodium alginate solution at 10-25 deg.c, and light shielding reaction for 12-24 hr; adding polyethylene glycol to react for 0.5-2h, dialyzing in deionized water, drying, and grinding to obtain aldehyde-terminated sodium alginate powder;
the aldehyde-terminated gelatin is synthesized by the following method: adding sodium periodate into 1-4wt% gelatin solution at 10-25 deg.c, and light-shielding reaction for 12-24 hr; adding polyethylene glycol to react for 0.5-2h, dialyzing in deionized water, drying, and grinding to obtain aldehyde group-terminated gelatin powder;
the aldehyde-terminated hyaluronic acid is synthesized by the following method: adding sodium periodate into 1-4wt% hyaluronic acid solution at 10-25 deg.C, and reacting for 12-24h in dark; adding polyethylene glycol to react for 0.5-2h, dialyzing in deionized water, drying, and grinding to obtain aldehyde-terminated hyaluronic acid powder;
the aldehyde-terminated genipin is synthesized by the following method: adding sodium periodate into 1-4wt% genipin solution at 10-25 deg.C, and reacting for 12-24h in dark; adding polyethylene glycol to react for 0.5-2h, dialyzing in deionized water, drying, and grinding to obtain aldehyde-terminated genipin powder;
the aldehyde-terminated guar gum is synthesized by the following method: adding sodium periodate into 1-4wt% guar gum solution at 10-25 deg.C, and reacting for 12-24h in dark; and then adding polyethylene glycol to react for 0.5-2h, dialyzing in deionized water, drying, and grinding to obtain the aldehyde-terminated guar gum powder.
8. The method for preparing a hemostatic material capable of achieving rapid hemostasis according to any one of claims 1 and 3-7, comprising the steps of preparing a first component, preparing a second component and preparing a patch, wherein:
the first component is prepared by dissolving chitosan components in deionized water at 20-50 ℃, and adding a monomer, a cross-linking agent, N-acryloyloxy succinimide and a photoinitiator to obtain a first component solution; wherein the monomer is an acrylic acid monomer, an acrylamide monomer or an N-isopropyl acrylamide monomer;
the second component is prepared by mixing non-aldehydized polysaccharide and dialdehyde polysaccharide in metal cation salt solution at 10-25 ℃ to obtain second component solution; wherein the synthesis process of the dialdehyde polysaccharide comprises the following steps: dissolving non-aldehydic polysaccharide in deionized water at 10-25 deg.c to obtain 1-4wt% non-aldehydic polysaccharide solution, adding sodium periodate into the non-aldehydic polysaccharide solution for light-shielding reaction for 12-24 hr, and adding polyglycol for reaction for 0.5-2 hr; then, dialyzing the reaction system in deionized water, drying, and grinding to obtain dialdehyde polysaccharide;
preparation of the patch: mixing the first component solution and the second component solution to obtain a preset solution; and then, injecting the preset solution into a patch mold, carrying out ultraviolet polymerization and drying to obtain the hemostatic patch.
9. The method for preparing a hemostatic material with rapid hemostasis function as claimed in claim 8, wherein the patch is prepared by injecting the preset solution into a patch mold with a depth of 500 μm and made of glass, polymerizing for 10-60min under 365nm ultraviolet light, opening the mold, and drying in nitrogen for 24h.
10. A method for preparing a hemostatic material capable of achieving rapid hemostasis according to any one of claims 2 and 3-7, comprising the steps of preparing a first component, preparing a second component and preparing a sponge, wherein:
the first component is prepared by dissolving chitosan components in deionized water at 20-50 ℃, and adding a monomer, a cross-linking agent, N-acryloyloxy succinimide and a photoinitiator to obtain a first component solution; wherein the monomer is an acrylic acid monomer, an acrylamide monomer or an N-isopropyl acrylamide monomer;
the second component is prepared by mixing non-aldehydic polysaccharide and dialdehyde polysaccharide in metal cation salt solution at 10-25 deg.C to obtain second component solution; wherein the synthesis process of the dialdehyde polysaccharide comprises the following steps: dissolving non-aldehydized polysaccharide in deionized water at 10-25 deg.c to obtain 1-4wt% non-aldehydized polysaccharide solution, adding sodium periodate into the non-aldehydized polysaccharide solution for light-shielding reaction for 12-24 hr, and adding polyglycol for reaction for 0.5-2 hr; then, dialyzing the reaction system in deionized water, drying, and grinding to obtain dialdehyde polysaccharide;
preparing the sponge: mixing the first component solution and the second component solution to obtain a preset solution; and then, injecting the preset solution into a mold, carrying out ultraviolet polymerization, then putting the gelatinized sample into a PBS (phosphate buffer solution) solution for swelling treatment, and after complete swelling, carrying out freeze drying to obtain the hemostatic sponge.
11. A method for preparing a hemostatic material with rapid hemostasis according to claim 10, wherein for the preparation of the sponge, the uv polymerization is specifically polymerization under 365nm uv light for 10-60min; the freeze drying is carried out by pre-freezing at-80 ℃ and then freeze drying at-40 ℃.
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