Preparation method of high-adhesion hemostatic antibacterial degradable hydrogel based on irradiation crosslinking and hydrogel

Abstract

The application provides a preparation method of high-adhesion hemostatic antibacterial degradable hydrogel based on irradiation crosslinking, and belongs to the technical field of biomedical materials, and comprises the following steps: polyvinyl alcohol and tannic acid are dissolved in an ethanol solution to obtain a mixed solution; the mixed solution is poured into a mold, and after being subjected to freezing treatment and then thawing, a non-adhesion outer layer is obtained; trimethylolaminomethane is added to the mixed solution, and is dissolved to obtain a Tris buffer mixed solution; lipoic acid is added to the Tris buffer mixed solution, and is fully dissolved to obtain a reaction solution; the reaction solution is poured into the mold to cover the non-adhesion outer layer, and a high-energy ray with a dose of 1-10 kGy is used to irradiate and treat the solution in the mold, so that a high-adhesion hemostatic antibacterial degradable hydrogel is obtained. The degradable hydrogel prepared by the method can quickly stop bleeding, has good controllable bioadhesion characteristics and mechanical strength, and has good biological activity and biocompatibility, and has application value in the fields of antibiosis, anti-inflammation, antioxidation and skin defect repair. The application further provides a high-adhesion hemostatic antibacterial degradable hydrogel based on irradiation crosslinking.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of biomedical materials, and particularly relates to a preparation method of high-adhesion hemostatic antibacterial degradable hydrogel based on irradiation crosslinking and the hydrogel. BACKGROUND

[0002] Frequent bleeding and exudation in tissue damage, in vivo and in wound surgery leads to difficult wound healing, causing great distress to human life and health. Physical methods such as sutures, staples and physiological hemostasis of the body cannot achieve rapid hemostasis, so other exogenous materials are used to accelerate hemostasis and have attracted great attention and research. With the in-depth study of hemostatic materials, absorbable hemostatic materials have become a research focus. At present, the main absorbable hemostatic materials in domestic and foreign research are gelatin, collagen, fibrin glue, oxidized cellulose, chitosan and sodium alginate, which basically meet the hemostatic needs of general trauma, but cannot well solve the problem of in vivo damage and postoperative wound hemostasis. In addition, the mechanical strength matching of the existing absorbable hemostatic materials is still not ideal, and the preparation of hydrogel still needs more initiators and crosslinking agents and other additives, which is still a potential safety problem.

[0003] Hydrogel is a three-dimensional network gel with high water content, similar to the natural extracellular matrix and has its characteristics, and is widely used in the field of biomedical materials, such as wound dressing, cell culture and tissue repair. Giving the tissue adhesion of hydrogel can form covalent bonds or non-covalent bonds with the tissue to physically close the bleeding wound and promote tissue repair. The adhesive hydrogel not only has wet tissue adhesion, rapid hemostasis and good biocompatibility, but also needs tough mechanical strength and applicability to match irregular target sites.

[0004] At present, the existing hemostatic hydrogel materials are generally toxic to the human body and cannot be completely biodegraded. For example, CN201510155744.5 “Method for preparing chitosan-based hydrogel by high-energy ray irradiation”, in the preparation process, it is inevitable to use toxic solvents and additives such as acrylamide, which is not conducive to the use of human wound healing, and its anti-inflammatory and antibacterial functions are not enough to meet the wound healing conditions. In addition, the preparation process of the existing hydrogel is complicated, the operation is complex, and the cost is high, which is not conducive to large-scale production and application. SUMMARY

[0005] In order to obtain a new type of hemostatic hydrogel material, the present application provides a preparation method of high-adhesion hemostatic antibacterial degradable hydrogel based on irradiation crosslinking. The degradable hydrogel prepared by the method can quickly stop bleeding, has good controllable biological adhesion characteristics and mechanical strength, and has good biological activity and biocompatibility, and has application value in the fields of antibacterial, anti-inflammatory, antioxidant and skin defect repair.

[0006] The application also provides a high-adhesion hemostatic antibacterial degradable hydrogel based on irradiation crosslinking.

[0007] The application achieves the above technical effects through the following technical solutions.

[0008] The application provides a preparation method of a high-adhesion hemostatic antibacterial degradable hydrogel based on irradiation crosslinking, and the preparation method comprises the following steps:

[0009] Dissolve polyvinyl alcohol and tannic acid in an ethanol solution together to obtain a mixed solution;

[0010] Pour the mixed solution into a mold, freeze treat, and then thaw to obtain a non-adhesion outer layer;

[0011] Add Tris buffer to the mixed solution, dissolve, and obtain a Tris buffer mixed solution;

[0012] Add thioctic acid to the Tris buffer mixed solution, fully dissolve, and obtain a reaction solution;

[0013] Pour the reaction solution into the mold to cover the non-adhesion outer layer, and irradiate the solution in the mold with high-energy rays at a dose of 1-10 kGy to obtain a high-adhesion hemostatic antibacterial degradable hydrogel.

[0014] Further, the step of dissolving polyvinyl alcohol and tannic acid in an ethanol solution together to obtain a mixed solution specifically comprises the following steps:

[0015] Dissolve polyvinyl alcohol in an ethanol solution at 80-90 DEG C to obtain a polyvinyl alcohol solution;

[0016] Add tannic acid to the polyvinyl alcohol solution to dissolve and obtain a mixed solution;

[0017] The ethanol solution is obtained by mixing ethanol and water at a volume ratio of 1:1;

[0018] In the mixed solution, the mass fraction of polyvinyl alcohol is 1%-10%, and the mass fraction of tannic acid is 1%-10%.

[0019] Further, the step of pouring the mixed solution into a mold, freeze treating, and then thawing to obtain a non-adhesion outer layer specifically comprises the following steps:

[0020] Pour the mixed solution into a mold, freeze at-20±5 DEG C for 2±0.2 h, and then thaw to obtain a non-adhesion outer layer.

[0021] Further, the trimethylolamine is added to the mixed solution to dissolve, and a Tris buffer mixed solution is obtained; lipoic acid is added to the Tris buffer mixed solution to dissolve, and a reaction liquid is obtained, specifically including:

[0022] The trimethylolamine is added to the mixed solution to dissolve, and a Tris buffer mixed solution is obtained;

[0023] The lipoic acid is added to the Tris buffer mixed solution to dissolve at 70±2°C for 3±0.5h, and a reaction liquid is obtained;

[0024] In the reaction liquid, the mass fraction of trimethylolamine is 1%-10%, and the mass fraction of lipoic acid is 5%-30%.

[0025] Further, the reaction liquid is poured into the mold to cover the non-adhesion outer layer, and the solution in the mold is subjected to irradiation treatment by high-energy rays at a dose of 1-10kGy, and a high-adhesion hemostatic antibacterial degradable hydrogel is obtained, specifically including:

[0026] The reaction liquid is poured into the mold to cover the non-adhesion outer layer, and the solution in the mold is subjected to irradiation treatment by high-energy rays at a dose of 1-10kGy for 0.1-24h, and a high-adhesion hemostatic antibacterial degradable hydrogel is obtained.

[0027] Further, the thickness of the non-adhesion outer layer is 1-10mm, and the total thickness of the high-adhesion hemostatic antibacterial degradable hydrogel is 2-20mm.

[0028] Based on the same inventive concept, the present application provides a high-adhesion hemostatic antibacterial degradable hydrogel based on irradiation cross-linking, which is prepared by the above-mentioned preparation method of the high-adhesion hemostatic antibacterial degradable hydrogel based on irradiation cross-linking.

[0029] Based on the same inventive concept, the present application provides a high-adhesion hemostatic antibacterial degradable hydrogel based on irradiation cross-linking, which includes an adhesion hydrogel inner layer and a non-adhesion hydrogel outer layer, and a continuous gradual transition layer between the adhesion hydrogel inner layer and the non-adhesion hydrogel outer layer.

[0030] The adhesion hydrogel inner layer includes the following components in terms of mass fraction:

[0031] Tannic acid <10%, trimethylolamine (Tris) 1%-10%, tannic acid grafted polysulfur lipoic acid 5%-30%, polyvinyl alcohol 1%-10%, and ethanol solution 40%-92%;

[0032] The non-adhesion hydrogel outer layer includes the following components in terms of mass fraction:

[0033] Tannin acid 1-10%, polyvinyl alcohol 1-10%, ethanol solution 80-98%.

[0034] Further, the thickness of the adherent hydrogel inner layer is 100-200 μm, and the thickness of the non-adherent hydrogel outer layer is 100-200 μm.

[0035] Based on the same inventive concept, the application also provides a use of the high-adhesion hemostatic antibacterial degradable hydrogel based on irradiation crosslinking in preparation of any one of a hemostatic material, a hemostatic medical device, an antibacterial material, an anti-inflammatory material, an antioxidant material and a skin defect repair material.

[0036] The one or more technical solutions in the embodiments of the application have at least the following technical effects or advantages:

[0037] 1. The application discloses a preparation method of a high-adhesion hemostatic antibacterial degradable hydrogel based on irradiation crosslinking. The hydrogel has a mechanical property matching the strength of tissue through irradiation crosslinking. The prepared hydrogel can close a wound through physical adhesion and form covalent or non-covalent bonds with a tissue interface to enhance the adhesion of the hydrogel and the tissue interface, has good controllable biological adhesion characteristics and mechanical strength, can quickly stop bleeding, has good biological activity and biocompatibility, and can be completely biodegraded. The hydrogel has application values in the fields of antibiosis, anti-inflammation, antioxidation and skin defect repair, can be particularly used for preparing an oral ulcer patch, can be used for in-vivo wound closure and hemostasis, can be safely degraded in the body, and overcomes the problems of addition of toxic adjuvants in a preparation process of an existing hydrogel and poor adhesion strength of the hydrogel and the tissue interface.

[0038] 2. The application discloses a high-adhesion hemostatic antibacterial degradable hydrogel based on irradiation crosslinking. The hydrogel has a gradient structure, and a water gel containing polyvinyl alcohol and tannin acid is used as an outer layer, and a water gel containing tannin acid grafted with polysulphoxine and polyvinyl alcohol is used as an adherent inner layer. There is no obvious boundary between the inner and outer layers. The inner network is interacted through multiple hydrogen bonds, has strong cohesion, is tightly combined, has basically consistent mechanical strength, and has no delamination phenomenon. In a stress-strain curve test, no interlayer cracking phenomenon occurs. The inner layer of the hydrogel has high-strength wet tissue adhesion capacity, is used for adhering to a wound surface, effectively closes the wound and resists bacteria, and accelerates wound healing. The outer layer has no adhesion, is used for preventing adhesion of an in-vivo or in-vitro wound, and provides certain mechanical strength and antibacterial performance. The hydrogel can realize rapid wound closure treatment, forms a physical barrier to provide a good environment for wound healing, and provides a new method for accelerating wound healing.

[0039] 3. The application discloses a high-adhesion hemostatic antibacterial degradable hydrogel based on irradiation crosslinking, which is a high-adhesion hemostatic antibacterial degradable hydrogel with a continuous gradient structure, and catechol active ingredients-tannic acid and thioctic acid with anti-inflammatory and antioxidant properties are directly added into polyvinyl alcohol to obtain the hydrogel with good controllable bioadhesion properties and mechanical strength; compared with a traditional hemostatic antibacterial degradable hydrogel system, the hydrogel has excellent elasticity and mechanical properties, can be tailored into various shapes according to requirements, and the preparation method of the hydrogel is simple and raw materials are easy to obtain. BRIEF DESCRIPTION OF DRAWINGS

[0040] In order to more clearly illustrate the technical solutions in the embodiments of the present application, the drawings needed to be used in the following embodiment description will be briefly introduced. Obviously, the drawings in the following description are some embodiments of the present application, and other drawings can be obtained by those skilled in the art without any creative effort on the basis of these drawings.

[0041] Figure 1 The hydrogel of the present application is shown in the following photographs: the left photograph is a length measurement photograph; the middle photograph is a width measurement photograph; and the right photograph is an actual hydrogel cuboid sample.

[0042] Figure 2 The microstructure of the hydrogel of the present application is shown in the following photographs: the left photograph is a microstructure photograph of a hydrogel containing 5% of tris-hydroxymethyl aminomethane, 20% of tannic acid grafted polysulfine acid and 3% of polyvinyl alcohol, and the total content of tannic acid is 3%; the middle photograph is a microstructure photograph of a hydrogel containing 5% of tris-hydroxymethyl aminomethane, 20% of tannic acid grafted polysulfine acid and 6% of polyvinyl alcohol, and the total content of tannic acid is 6%; and the right photograph is a microstructure photograph of a hydrogel containing 5% of tris-hydroxymethyl aminomethane, 20% of tannic acid grafted polysulfine acid and 10% of polyvinyl alcohol, and the total content of tannic acid is 10%.

[0043] Figure 3 The effect of the hydrogel of the present application on hemostasis and tissue defect repair is shown in the following photographs: the left photograph is a photograph of liver injury of a mouse; the left middle photograph is a photograph of the hydrogel attached to a wound of the liver injury for hemostasis; the right middle photograph is a photograph of the hydrogel attached to the wound of the liver injury of the mouse and no bleeding is observed; and the right photograph is a photograph of the repair effect of the hydrogel on the wound of the liver injury of the mouse. DETAILED DESCRIPTION

[0044] The present application will be described in detail below in combination with specific embodiments and examples, and the advantages and various effects of the present application will be more clearly presented. Those skilled in the art should understand that these specific embodiments and examples are used to illustrate the present application, rather than limit the present application.

[0045] Throughout the specification, unless otherwise specifically indicated otherwise, the terms used herein are understood to be as commonly used in the art. Therefore, unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the present application belongs. If there is a contradiction, the present specification takes priority.

[0046] Unless otherwise specifically indicated, the various raw materials, reagents, instruments and equipment used in the present application can be purchased on the market or can be prepared by existing methods.

[0047] Unless otherwise specified, the experimental methods used in the following examples are conventional methods.

[0048] The technical principle of the present application is as follows:

[0049] The present application is a preparation method of a high-adhesion hemostatic antibacterial degradable hydrogel based on irradiation crosslinking, which comprises:

[0050] Polyvinyl alcohol and tannic acid are dissolved together in an ethanol solution to obtain a mixed solution;

[0051] The mixed solution is poured into a mold, and after freezing treatment and thawing, a non-adhesive outer layer is obtained;

[0052] Tris buffer mixed solution is obtained by adding Tris to the mixed solution and dissolving it;

[0053] The reaction solution is obtained by adding thioctic acid to the Tris buffer mixed solution and dissolving it thoroughly;

[0054] The reaction solution is poured into the mold to cover the non-adhesive outer layer, and the solution in the mold is irradiated with a high-energy ray at a dose of 1-10 kGy to obtain a high-adhesion hemostatic antibacterial degradable hydrogel.

[0055] In the present application, after the mixed solution is poured into the mold, freezing and thawing are carried out, which is beneficial to the physical crosslinking of the polyvinyl alcohol in the solution to form hydrogen bonds between the high molecular chains, so as to form a gel and quickly form a shape.

[0056] In the present application, the polyvinyl alcohol in the non-adhesive outer layer mainly functions to form a high molecular network to provide a skeleton support through irradiation crosslinking; tannic acid is a catechol active ingredient, which provides good antibacterial properties and biocompatibility.

[0057] In the application, the polyvinyl alcohol in the adherent inner layer is mainly cross-linked by irradiation to form a high molecular network to provide skeleton support; tannic acid is a catechol active ingredient, which provides good antibacterial properties and biocompatibility; trimethylamine is mainly used to adjust the acidity and alkalinity of the solution and keep it neutral; lipoic acid mainly provides strong wet tissue adhesion and provides antibacterial and antioxidant properties.

[0058] In the application, after lipoic acid is added to the Tris buffer mixed solution and dissolved, lipoic acid is ring-opening polymerized into poly-lipoic acid, and the reaction of tannic acid grafting poly-lipoic acid is continued to be complete.

[0059] In the application, the solution in the mold is irradiated by high-energy rays with a dose of 1-10 kGy. The polyvinyl alcohol in the hydrogel will undergo cross-linking reaction to form a high molecular network, further improving its mechanical properties. The tannic acid-lipoic acid network in the hydrogel will undergo a certain degree of irradiation degradation reaction, on the one hand, to balance the cohesion and adhesion to improve the overall adhesion strength, and on the other hand, to expose more adhesion groups to the adhesion layer to improve the adhesion strength.

[0060] Further, the polyvinyl alcohol and tannic acid are dissolved in the ethanol solution to obtain a mixed solution, which specifically includes:

[0061] The polyvinyl alcohol is dissolved in the ethanol solution at 80-90°C to obtain a polyvinyl alcohol solution;

[0062] Tannic acid is added to the polyvinyl alcohol solution to dissolve and obtain a mixed solution;

[0063] The ethanol solution is obtained by mixing ethanol and water at a volume ratio of 1:1.

[0064] In the mixed solution, the mass fraction of polyvinyl alcohol is 1%-10%, and the mass fraction of tannic acid is 1%-10%.

[0065] In the application, the ethanol and water are mixed at a volume ratio of 1:1. The advantage is that the solute-solvent interaction is used to avoid too high viscosity of the solution, quickly dissolve the polyvinyl alcohol and tannic acid, and promote the dissolution of the later-added lipoic acid, control the ring-opening polymerization of lipoic acid, and the role of ethanol is to induce the ring-opening polymerization of lipoic acid into poly-lipoic acid.

[0066] Further, the trimethylamine is added to the mixed solution, dissolved to obtain a Tris buffer mixed solution, and lipoic acid is added to the Tris buffer mixed solution, fully dissolved to obtain a reaction solution, which specifically includes:

[0067] The trimethylamine is added to the mixed solution, dissolved to obtain a Tris buffer mixed solution;

[0068] The lipoic acid is added to the Tris buffer mixed solution, and then dissolved at 70±2 DEG C under stirring for 3±0.5 h to obtain a reaction solution;

[0069] In the reaction solution, the mass fraction of the tris base is 1%-10%, and the mass fraction of the lipoic acid is 5%-30%.

[0070] In the application, the tris base and the lipoic acid are added to the mixed solution, and then stirred at 70±2 DEG C for 3±0.5 h, so that the polymerization degree of the lipoic acid and the crosslinking degree of the tannic acid-poly-lipoic acid network are regulated, and thus the hydrogel system with different adhesion strengths is obtained.

[0071] Further, the reaction solution is poured into the mold to cover the non-adhesion outer layer, and the solution in the mold is subjected to irradiation treatment by using high-energy rays with a dose of 1-10 kGy to obtain the high-adhesion hemostatic antibacterial degradable hydrogel, and the method specifically comprises the following steps:

[0072] The reaction solution is poured into the mold to cover the non-adhesion outer layer, and then the solution in the mold is subjected to irradiation treatment by using high-energy rays with a dose of 1-10 kGy, and the irradiation time is 0.1-24 h to obtain the high-adhesion hemostatic antibacterial degradable hydrogel.

[0073] In the application, the high-energy ray dose is 1-10 kGy, which can accurately control the irradiation dose and accurately regulate the mechanical strength and adhesion strength of the hydrogel, and the irradiation time is 0.1-24 h, which is short, easy to operate, accurate in control, and makes the reaction complete.

[0074] Based on the same inventive concept, the application provides a high-adhesion hemostatic antibacterial degradable hydrogel based on irradiation crosslinking, which comprises an adhesion hydrogel inner layer and a non-adhesion hydrogel outer layer, and a continuous gradual transition layer between the adhesion hydrogel inner layer and the non-adhesion hydrogel outer layer.

[0075] The adhesion hydrogel inner layer comprises the following components in terms of mass fraction:

[0076] Tannic acid 1%-10%, tris base 1%-10%, tannic acid grafted poly-lipoic acid 5%-30%, polyvinyl alcohol 1%-10%, and ethanol solution 40%-92%;

[0077] The non-adhesion hydrogel outer layer comprises the following components in terms of mass fraction:

[0078] Tannic acid 1%-10%, polyvinyl alcohol 1%-10%, and ethanol solution 80%-98%.

[0079] The tannic acid mass fraction in the hydrogel of the application is 1-10%, which can accurately regulate the content of catechol in the hydrogel and the antibacterial property thereof, the Tris mass fraction is 1-10%, which has the advantage of accurately regulating the acidity and alkalinity of the hydrogel, the polyvinyl alcohol mass fraction is 1-10%, which accurately controls the content of polyvinyl alcohol polymer chains in the hydrogel, thereby controlling the mechanical strength of the hydrogel, and the tannic acid grafted polysulfated fatty acid is 5-30%, which has the advantage of more accurately controlling the crosslinking density of the polymer network inside the hydrogel. If the content of each component is too high or too low, the hydrogel formation, mechanical strength, adhesive strength, antibacterial property and the like of the hydrogel cannot reach the expected indicators.

[0080] The preparation method of the high-adhesion hemostatic antibacterial degradable hydrogel based on irradiation crosslinking and the hydrogel will be described in detail below in combination with examples and experimental data.

[0081] Example 1

[0082] The preparation method of the high-adhesion hemostatic antibacterial degradable hydrogel based on irradiation crosslinking in this example is as follows:

[0083] 1) 2.4g of polyvinyl alcohol was dispersed in 17.6mL of water and 17.6mL of ethanol mixed solvent, and heated and stirred at 90℃ for 1h to completely dissolve the polyvinyl alcohol, obtaining a polyvinyl alcohol solution with a mass fraction of 6%;

[0084] 2) 2.4g of tannic acid (TA) was dissolved in the polyvinyl alcohol solution with a mass fraction of 6%, and stirred to completely dissolve, obtaining a tannic acid polyvinyl alcohol solution A with a mass fraction of 6%;

[0085] 3) The tannic acid polyvinyl alcohol solution A was poured into a mold, frozen at -20℃ for 2h, and then completely thawed to form a non-adhesive lower layer;

[0086] 4) Another portion of the tannic acid polyvinyl alcohol solution A was taken, 5g of Tris and 10g of lauric acid (LA) were added, heated at 70℃, and stirred vigorously (400r / min) for 3h, and then cooled (cooling rate 20℃ / h) to room temperature to obtain solution B;

[0087] 5) The solution B was poured into the mold and covered on the non-adhesive lower layer, and then packaged;

[0088] 6) The packaged hydrogel of step 5) was subjected to irradiation treatment at room temperature by 5kGy dose of 60 Co high-energy gamma rays, the irradiation time was 8h, after the irradiation was completed, the mold was removed, and a high-adhesion hemostatic antibacterial degradable hydrogel was obtained.

[0089] The hydrogel prepared in Example 1 was used for rat liver wound hemostasis and tissue repair experiments.

[0090] Rats are placed in supine position, and after anesthesia using a special anesthetic device, the abdomen is disinfected with 70% ethanol and prepared for skin, the abdominal cavity is opened to find the right lobe of the liver and wrapped with sterile gauze, a special mold is used to make a wound with a diameter of 8mm on the right lobe of the liver, the adhesive hydrogel is laid on the wound, gently pressed, and the bleeding is observed and collected in a special test tube with filter paper, until there is no obvious rebleeding, and the amount of bleeding is recorded; the hydrogel adhered to the wound of the liver is implanted into the rat body together with the liver, and the healing of the wound of the rat liver is observed and recorded at 1 day, 3 days and 7 days after implantation, respectively.

[0091] Figure 1 It is a hydrogel physical picture of the application: the left picture is a length measurement picture; the middle picture is a width measurement picture; and the right picture is an actual hydrogel cuboid sample.

[0092] Figure 2 It is a hydrogel microstructure picture of the application: the left, middle and right pictures are respectively: a hydrogel microstructure picture of 5% tris-hydroxymethyl aminomethane, 20% tannic acid grafted polysulphoxine and 3% polyvinyl alcohol, a hydrogel microstructure picture of 5% tris-hydroxymethyl aminomethane, 20% tannic acid grafted polysulphoxine and 6% polyvinyl alcohol, and a hydrogel microstructure picture of 5% tris-hydroxymethyl aminomethane, 20% tannic acid grafted polysulphoxine and 10% polyvinyl alcohol. With the increase of the content of polyvinyl alcohol and tannic acid, the roughness in the microstructure is reduced, the mechanical strength of the hydrogel is increased, the cohesion is improved, and the adhesive strength of the hydrogel is decreased.

[0093] Figure 3 It is an effect picture of the application for hemostasis and tissue defect repair of the hydrogel: the left one picture is a mouse liver injury picture; the left two pictures are hydrogel adhesion and hemostasis pictures of the liver injury wound; the right two pictures are hydrogel adhesion pictures of the mouse liver injury wound without bleeding; and the right one picture is a hydrogel repair effect picture of the mouse liver injury wound. The liver injury wound is made by a mold, and the effect of hydrogel adhesion, hemostasis, wound closure and tissue repair is detected.

[0094] Finally, it should be noted that the terms "comprising", "including", or any other variant thereof are intended to cover non-exclusive inclusions, so that a process, method, article or device including a series of elements not only includes those elements, but also includes other elements not explicitly listed, or inherent to such a process, method, article or device.

[0095] While the preferred embodiments of the application have been described, additional variations and modifications can be made to these embodiments by those skilled in the art once they have the benefit of the present disclosure without departing from the spirit and scope of the application. Accordingly, it is intended that the appended claims include all such modifications and variations as fall within the scope of the present application.

[0096] It is apparent that those skilled in the art can make various changes and modifications to the application without departing from the spirit and scope of the application. It is therefore intended that the present application cover all such changes and modifications that are within its scope.

Claims

1. A method for preparing a highly adhesive hemostatic and antibacterial degradable hydrogel based on radiation cross-linking, characterized in that: The preparation method comprises: dissolving polyvinyl alcohol and tannic acid in an ethanol solution to obtain a mixed solution; pouring the mixed solution into a mold, freezing it and then thawing it to obtain a non-adhesive outer layer; Adding tris(hydroxymethylaminomethane) to the mixed solution and dissolving it to obtain a Tris buffer mixed solution; adding lipoic acid to the Tris buffer mixed solution and fully dissolving it to obtain a reaction solution; Pour the reaction solution into the mold, cover the non-adhesive outer layer, and irradiate the solution in the mold with high-energy radiation at a dose of 1 to 10 kGy to obtain a highly adhesive, hemostatic, antibacterial, and degradable hydrogel; The ethanol solution is obtained by mixing ethanol and water in a volume ratio of 1:1; In the mixed solution, the mass fraction of polyvinyl alcohol is 1%-10%, and the mass fraction of tannic acid is 1%-10%; In the reaction solution, the mass fraction of tris(hydroxymethyl)aminomethane is 1%-10%, and the mass fraction of lipoic acid is 5%-30%.

2. The method for preparing a highly adhesive hemostatic and antibacterial degradable hydrogel based on radiation cross-linking according to claim 1, characterized in that: The method of dissolving polyvinyl alcohol and tannic acid in an ethanol solution to obtain a mixed solution specifically comprises: dissolving polyvinyl alcohol in ethanol solution at 80-90° C. to obtain a polyvinyl alcohol solution; Tannic acid is added to the polyvinyl alcohol solution to dissolve it, thereby obtaining a mixed solution.

3. The method for preparing a highly adhesive hemostatic and antibacterial degradable hydrogel based on radiation cross-linking according to claim 1, characterized in that: The mixed solution is poured into a mold, and then thawed after freezing to obtain a non-adhesive outer layer, specifically comprising: The mixed solution is poured into a mold, frozen at -20±5°C for 2±0.2h, and then thawed to obtain a non-adhesive outer layer.

4. The method for preparing a highly adhesive hemostatic and antibacterial degradable hydrogel based on radiation cross-linking according to claim 1, characterized in that: adding tris(hydroxymethylaminomethane) to the mixed solution and dissolving it to obtain a Tris buffer mixed solution; Adding lipoic acid to the Tris buffer mixed solution and fully dissolving it to obtain a reaction solution specifically comprises: Adding tris(hydroxymethylaminomethane) to the mixed solution and dissolving it to obtain a Tris buffer mixed solution; Add lipoic acid to the Tris buffer mixed solution, and then stir at 70±2° C. for 3±0.5 h to dissolve to obtain a reaction solution.

5. The method for preparing a highly adhesive hemostatic and antibacterial degradable hydrogel based on radiation cross-linking according to claim 1, characterized in that: The step of pouring the reaction solution into the mold to cover the non-adhesive outer layer and irradiating the solution in the mold with high-energy radiation at a dose of 1 to 10 kGy to obtain a highly adhesive, hemostatic, antibacterial, and degradable hydrogel specifically comprises: The reaction solution is poured into the mold to cover the non-adhesive outer layer, and then the solution in the mold is irradiated with high-energy rays at a dose of 1 to 10 kGy for a time of 0.1 to 24 hours to obtain a highly adhesive hemostatic and antibacterial degradable hydrogel.

6. The method for preparing a highly adhesive hemostatic and antibacterial degradable hydrogel based on radiation cross-linking according to claim 1, characterized in that: The thickness of the non-adhesive outer layer is 1 to 10 mm, and the total thickness of the highly adhesive hemostatic and antibacterial degradable hydrogel is 2 to 20 mm.

7. A highly adhesive hemostatic and antibacterial degradable hydrogel based on radiation cross-linking, characterized in that: The hydrogel is prepared by the method for preparing a high-adhesion, hemostatic, antibacterial and degradable hydrogel based on radiation cross-linking according to any one of claims 1 to 6.

8. A highly adhesive hemostatic and antibacterial degradable hydrogel based on radiation cross-linking, characterized in that: The hydrogel comprises an adhesive hydrogel inner layer and a non-adhesive hydrogel outer layer, and a continuous gradient transition layer is provided between the adhesive hydrogel inner layer and the non-adhesive hydrogel outer layer; The adhesive hydrogel inner layer comprises the following components by mass fraction: Tannic acid <10%, tris(hydroxymethyl)aminomethane 1%-10%, tannic acid grafted polylipoic acid 5%-30%, polyvinyl alcohol 1%-10%, ethanol solution 40%-92%; The non-adhesive hydrogel outer layer comprises the following components by mass fraction: Tannic acid 1%-10%, polyvinyl alcohol 1%-10%, ethanol solution 80%-98%.

9. The high-adhesion hemostatic and antibacterial degradable hydrogel based on radiation cross-linking according to claim 8, characterized in that: The thickness of the adhesive hydrogel inner layer is 100 to 200 μm, and the thickness of the non-adhesive hydrogel outer layer is 100 to 200 μm.

10. Use of the radiation-crosslinked high-adhesion hemostatic and antibacterial degradable hydrogel according to any one of claims 7 to 9 in the preparation of any one of hemostatic materials, antibacterial materials, anti-inflammatory materials, antioxidant materials and skin defect repair materials.

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