An adhesive antibacterial and antioxidant copper-containing hydrogel and preparation method thereof

Abstract

The present invention discloses an adhesive antibacterial and antioxidant copper-containing hydrogel and a preparation method thereof, and belongs to the fields of material technology, biomedicine, wound repair and medical device technology. The present invention introduces tannin polyphenol, polydopamine and copper ions into a gel system, uses tannin polyphenol / copper complex to initiate polymerization, and after compounding with polydopamine, can quickly kill bacterial pathogens, continuously remove wound free radicals, adjust oxidation balance, and promote wound healing. The adhesive antibacterial and antioxidant copper-containing hydrogel prepared by the present invention contains a polypropionic acid component, has good water absorption and water retention, high tensile strength, strong mechanical strength, and adjustable performance, and is conveniently applicable to various types and shapes of infected wounds.

Description

Technical Field

[0001] The invention belongs to the fields of material technology, biomedicine, wound repair and medical device technology, and specifically relates to an adhesive antibacterial and antioxidant copper-containing hydrogel and a preparation method thereof. Background Art

[0002] Wounds caused by high and low temperatures, mechanical forces, and diseases such as diabetes are prone to infection, leading to wound suppuration and ulceration, oxidative stress, vascular damage, and chronic inflammation, which makes it difficult to heal on their own. At present, gauze is often used in clinical dressing changes. The tissue at the wound ulcer is easily adhered to the gauze, which is easy to cause secondary damage during dressing changes. In addition, materials such as gauze and sponges cannot fit perfectly with wounds of various shapes, and there are often cases of tissue fluid leakage and repeated bacterial infection. The pain, fever, inflammatory response caused by wound infection and ulceration, and the discomfort caused by daily dressing changes have caused great pain to such patients. Therefore, a new type of adhesive antibacterial gel has been developed, which can not only sterilize for a long time and efficiently, but also effectively adhere to the wound surface to seal the wound, keep the wound surface breathable and moist, remove excessive reactive oxygen, regulate oxidative balance and immunity, promote angiogenesis, and promote wound healing, which is of great significance for the treatment of infected wounds. Summary of the invention

[0003] In view of the problems existing in the above-mentioned prior art, the present invention provides an adherent antibacterial and antioxidant copper-containing hydrogel and a preparation method thereof.

[0004] To achieve the above object, the present invention proposes the following technical solutions:

[0005] A method for preparing an adhesive antibacterial and antioxidant copper-containing hydrogel comprises the following steps:

[0006] 1) adding water to tannin polyphenol to prepare a tannin polyphenol aqueous solution, adding water to copper nitrate to prepare a copper nitrate solution, mixing the tannin polyphenol aqueous solution and the copper nitrate solution, centrifuging and washing, and dispersing the obtained tannin polyphenol / copper complex in water to obtain an initiator;

[0007] 2) adding water to ammonium persulfate to prepare an ammonium persulfate aqueous solution, and then mixing it with an acrylamide solution and acrylic acid to obtain a gel precursor solution;

[0008] 3) preparing a double-bond modified gelatin aqueous solution, and then mixing it with the gel precursor solution of step 2) and the initiator of step 1) to react to obtain a prefabricated gel;

[0009] 4) Soaking the prefabricated gel in step 3) in ultrapure water, then placing it in an aqueous solution of dopamine hydrochloride, adjusting the pH of the solution to alkaline, heating to polymerize the dopamine, washing, drying, and wiping off excess water on the surface to obtain an adherent antibacterial and antioxidant copper-containing hydrogel.

[0010] Furthermore, in step 1), the tannin polyphenol is one or more of tannic acid, catechin, gallic acid and anthocyanin; and the mass ratio of the tannin polyphenol to copper nitrate is 1:(5-8).

[0011] Furthermore, in step 2), the concentration of the aqueous ammonium persulfate solution is 0.5-2 mg / mL; the final concentration of acrylamide is 0.5-2.0 g / mL; and the final concentration of acrylic acid is 0.1-5.0 g / mL.

[0012] Furthermore, in step 3), the concentration of the double-bond modified gelatin aqueous solution is 10-100 mg / mL; the concentration of the initiator is 2-10 mg / mL; the reaction temperature is 10-35°C, and the reaction time is 10s-30min.

[0013] Furthermore, in step 4), the soaking parameters are: temperature 4-37°C, time 5-10 min, number of times 4-6 times; the concentration of the dopamine hydrochloride aqueous solution is 1-100 mg / mL; the number of washings after the dopamine polymerization is complete is 6-10 times.

[0014] Furthermore, in step 4), the pH is 8-10; the heating is carried out in a closed high-pressure reactor at a temperature of 60-140° C. for 2-24 hours.

[0015] The present invention also provides an adhesive antibacterial and antioxidant copper-containing hydrogel prepared by the preparation method.

[0016] The present invention also provides an application of an adherent antibacterial and anti-oxidative copper-containing hydrogel as an infected wound repair material.

[0017] Compared with the prior art, the present invention has the following beneficial effects:

[0018] (1) The adhesive antibacterial and antioxidant copper-containing hydrogel prepared by the present invention utilizes the coordination complexation of polydopamine and copper ions to reduce part of divalent copper to monovalent copper, forming active catalytic neutrality, generating enzyme-like activity, and reacting with hydrogen peroxide in different acid-base environments to provide hydroxyl radicals or remove hydroxyl radicals, superoxide anion radicals, etc.; divalent copper ions have a Fenton-like effect and can also react with hydrogen peroxide to produce hydroxyl radicals; polydopamine and tannin polyphenols as part of the initiator also have antioxidant effects; the hydrogel prepared in this way has both a highly efficient bactericidal effect and antioxidant ability by adjusting the acidity and alkalinity;

[0019] (2) The adhesive antibacterial and antioxidant copper-containing hydrogel prepared by the present invention, wherein the tannin polyphenol as a part of the initiator is evenly distributed in the gel medium, so that the material has a certain adhesion effect, and the introduction of polydopamine further enhances its adhesion performance to biological tissues such as skin, internal organs, and blood vessels;

[0020] (3) The adhesive antibacterial and antioxidant copper-containing hydrogel prepared by the present invention utilizes the complexation effect of polydopamine on copper ions to control the slow release of copper ions, thereby avoiding acute and chronic tissue poisoning caused by sudden ion release; extremely small amounts of copper ions effectively promote the proliferation of vascular endothelial cells, promote the formation of new blood vessels at the wound, and promote wound healing;

[0021] (4) In the preparation of the prefabricated gel, the present invention uses a catalytically active initiator formed by tannin polyphenol and copper to react with persulfate to quickly generate a large number of sulfate free radicals. The hydroxyl free energy generated by the reaction of sulfate free radicals with water quickly initiates double bond polymerization, thereby quickly forming a gel. This method saves time and energy costs and is suitable for mass production;

[0022] (5) The adhesive antibacterial and antioxidant copper-containing hydrogel prepared by the present invention contains a polyacrylic acid component, has good water absorption and water retention, high tensile strength, high mechanical strength, and adjustable performance, and is conveniently applicable to infected wounds of various types and shapes. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0024] Figure 1 TEM and element distribution diagram of the tannic acid / copper initiator in Example 3;

[0025] Figure 2 This is the NMR spectrum of the double bond modified gelatin in implementation case 3;

[0026] Figure 3 The prefabricated gel in Example 3 is implemented;

[0027] Figure 4 To implement the adhesion test of the prefabricated gel in Case 3, from left to right: 5mL sample bottle, No. 7 battery, 25g weight, 100g weight;

[0028] Figure 5 This is the adhesive antibacterial and antioxidant copper-containing hydrogel in Example 3 (left: before stretching; right: after stretching);

[0029] Figure 6 The antibacterial and antioxidant copper-containing hydrogel in the implementation case 3 is adhered to the surface of the medium;

[0030] Figure 7 To implement the anti-Escherichia coli effect of the adherent antibacterial and antioxidant copper-containing hydrogel in Case 3;

[0031] Figure 8 To implement the antioxidant effect of the adherent antibacterial and antioxidant copper-containing hydrogel in Case 3;

[0032] Fig. 9 The sample pictures of the antibacterial and antioxidant copper-containing hydrogel that can adhere in Example 3 are just prepared (left) and after being stored for one week in an environment of 25° C. and 55% humidity (middle and right);

[0033] Fig.10 This is a picture of the prefabricated gel sample prepared in Comparative Example 1;

[0034] Fig.11 This is the gelation condition in Comparative Example 2 where no tannin polyphenol / copper complex is used as an initiator and only ammonium persulfate is used as an initiator;

[0035] Fig.12 This is a picture of the adherent antibacterial and antioxidant copper-containing hydrogel sample prepared in Comparative Example 3. DETAILED DESCRIPTION

[0036] Various exemplary embodiments of the present invention will now be described in detail. This detailed description should not be considered as limiting the present invention, but should be understood as a more detailed description of certain aspects, features, and embodiments of the present invention.

[0037] It should be understood that the terms described in the present invention are only for describing special embodiments and are not intended to limit the present invention. In addition, for the numerical range in the present invention, it should be understood that each intermediate value between the upper and lower limits of the scope is also specifically disclosed. Each smaller range between the intermediate value in any stated value or stated range and any other stated value or intermediate value in the described range is also included in the present invention. The upper and lower limits of these smaller ranges can be independently included or excluded in the scope.

[0038] Unless otherwise indicated, all technical and scientific terms used herein have the same meanings as those generally understood by those skilled in the art. Although the present invention describes only preferred methods and materials, any methods and materials similar or equivalent to those described herein may also be used in the implementation or testing of the present invention. All documents mentioned in this specification are incorporated by reference to disclose and describe the methods and / or materials associated with the documents. In the event of a conflict with any incorporated document, the content of this specification shall prevail.

[0039] It will be apparent to those skilled in the art that various modifications and variations may be made to the specific embodiments of the present invention description without departing from the scope or spirit of the present invention. Other embodiments derived from the present invention description will be apparent to those skilled in the art. The present application description and examples are exemplary only.

[0040] The words “include,” “including,” “have,” “contain,” etc. used in this document are open-ended terms, meaning including but not limited to.

[0041] The "room temperature" and "normal temperature" mentioned in the present invention are all calculated as 25±2°C unless otherwise specified.

[0042] Copper ions effectively inhibit the growth of various bacteria and have a certain antibacterial effect on drug-resistant bacteria, but the onset is slow and the effect is not significant. Low concentrations of copper ions can effectively promote the proliferation of vascular endothelial cells to synthesize blood vessels, while high concentrations of copper ion residues can also be toxic to normal cells. Polydopamine has good tissue adhesion and antioxidant functions, but does not have antibacterial functions. After tannin polyphenols and polydopamine are complexed with copper ions, they can not only effectively control the release of copper ions, but also have enzyme-like activity to catalyze the decomposition of hydrogen peroxide, produce hydroxyl radicals, and enhance the bactericidal effect. In addition, under neutral conditions, tannin polyphenols and polydopamine have the function of removing active oxygen, and the enzyme-like activity produced after complexing with copper ions can further enhance its antioxidant effect. Therefore, the present invention introduces tannin polyphenols, polydopamine, and copper ions into the gel system together, which has very practical value and significance for the treatment of infected wounds.

[0043] After long-term research, the inventor found that although metal ions, such as copper, zinc, and silver, have antibacterial effects, for the entire healing process of complex wounds, infected wounds, and skin damage in diabetic patients, relying solely on antibacterial treatment cannot quickly and effectively heal the wound. Antioxidant treatment and elimination of oxidative stress are also very critical. The use of metal ions at high concentrations can easily lead to local tissue poisoning, while low concentrations cannot achieve good antibacterial effects. After tannin polyphenols and polydopamine are complexed with copper ions, a complex with catalytic activity is formed. On the one hand, hydrogen peroxide can be catalyzed to produce hydroxyl radicals under acidic conditions to enhance the bactericidal effect. Under neutral conditions, polyphenols and complexes have the effect of removing active oxygen; on the other hand, the complexation of polyphenols can effectively control the release of trace copper ions, promote angiogenesis, and avoid tissue poisoning. Based on this, the purpose of the present invention is to provide a method and process for preparing an adherent copper-containing hydrogel which can quickly kill bacterial pathogens, continuously remove free radicals from wounds, regulate oxidation balance, and promote wound healing by initiating polymerization of a tannin polyphenol / copper complex and compounding with polydopamine.

[0044] Specifically, the present invention provides a method for preparing an adherent antibacterial and antioxidant copper-containing hydrogel, comprising the following steps:

[0045] 1) adding water to tannin polyphenol to prepare a tannin polyphenol aqueous solution, adding water to copper nitrate to prepare a copper nitrate solution, mixing the tannin polyphenol aqueous solution and the copper nitrate solution, centrifuging and washing, and dispersing the obtained tannin polyphenol / copper complex in water to obtain an initiator;

[0046] 2) adding water to ammonium persulfate to prepare an ammonium persulfate aqueous solution, and then mixing it with an acrylamide solution and acrylic acid to obtain a gel precursor solution;

[0047] 3) preparing a double-bond modified gelatin aqueous solution, and then mixing it with the gel precursor solution of step 2) and the initiator of step 1) to react to obtain a prefabricated gel;

[0048] 4) Soaking the prefabricated gel in step 3) in ultrapure water, then placing it in an aqueous solution of dopamine hydrochloride, adjusting the pH of the solution to alkaline, heating to polymerize the dopamine, washing, drying, and wiping off excess water on the surface to obtain an adherent antibacterial and antioxidant copper-containing hydrogel.

[0049] In some embodiments, the water used in the present invention is ultrapure water.

[0050] In some embodiments, in step 1), the tannin polyphenol is one or more of tannic acid, catechin, gallic acid and anthocyanin, preferably tannic acid and gallic acid; the mass ratio of the tannin polyphenol to copper nitrate is 1:(5-8).

[0051] In step 2) of some embodiments, the concentration of the aqueous ammonium persulfate solution is 0.5-2 mg / mL; the final concentration of acrylamide is 0.5-2.0 g / mL; and the final concentration of acrylic acid is 0.1-5.0 g / mL.

[0052] In some embodiments, in step 3), the concentration of the double-bond modified gelatin aqueous solution is 10-100 mg / mL; the specific modification method is: take 20g of gelatin (type A) and place it in 200mL DPBS (Dole's phosphate buffered saline, pH7.4) buffer, heat it to 50°C, and stir until the gelatin is completely dissolved. Then add 10mL of methacrylic anhydride and heat the system temperature to 60°C. After the reaction lasts for 3h, 600mL of DPBS preheated at 40°C is added to the reaction system and stirred for 15min to terminate the reaction. The mixture is placed in a 14KDa dialysis bag and dialyzed in deionized water at 40°C for 7 days to remove side reactions and impurities. After the obtained dialysate is freeze-dried, the product is stored in a -80°C refrigerator.

[0053] In step 3) of some embodiments, the concentration of the initiator is 0.2-1.5 mg / mL; the reaction temperature is 10-35° C., and the reaction time is 10 s-30 min.

[0054] In step 3) of some embodiments, the volume ratio of the double-bond modified gelatin aqueous solution, the gel precursor solution and the initiator is (1-20):(40-80):(6-10), preferably 1:40:8, 2:8:0.6, 1:5:1.

[0055] In some embodiments, in step 4), the soaking parameters are: temperature 4-37°C, time 5-10 min, number of times 4-6 times; the concentration of the dopamine hydrochloride aqueous solution is 1-100 mg / mL; the number of washings after the dopamine polymerization is complete is 6-10 times.

[0056] In step 4) of some embodiments, the pH is 8-10; the heating temperature is 60-140° C., the time is 2-24 h, and the heating container is a high-pressure reactor.

[0057] The present invention also provides an adhesive antibacterial and antioxidant copper-containing hydrogel prepared by the preparation method.

[0058] The present invention also provides an application of an adherent antibacterial and anti-oxidative copper-containing hydrogel as an infected wound repair material.

[0059] Other raw materials used in the present invention are purchased from the market.

[0060] The following examples serve as further illustrations of the technical solutions of the present invention.

[0061] The water used in the following examples is ultrapure water.

[0062] Example 1

[0063] 1) 120 mL of a 5 mg / mL tannic acid aqueous solution and a 25 mg / mL copper nitrate aqueous solution were mixed and reacted at room temperature at a stirring speed of 600 r / min for 1 h, centrifuged at a centrifugal speed of 9000 r / min, washed repeatedly with ultrapure water for 4 times, and then dispersed in ultrapure water to obtain a tannic acid / copper active initiator with a concentration of 8 mg / mL.

[0064] 2) Prepare a 0.5 mg / mL ammonium persulfate aqueous solution, dissolve acrylamide and acrylic acid therein to make the final concentration of both reach 0.5 g / mL, and record it as a gel precursor solution.

[0065] 3) 10 μL of 10 mg / mL double-bond modified gelatin aqueous solution was mixed with 400 μL of gel precursor solution, and then 80 μL of initiator was added, and the prefabricated gel was obtained after waiting at room temperature for 30 minutes.

[0066] 4) The prefabricated gel was immersed and washed 5 times in ultrapure water at room temperature, and then placed in an aqueous solution containing 10 mg / mL dopamine hydrochloride. The solution was adjusted to pH = 8 by adding 1 M sodium hydroxide alkaline solution. After the reaction was closed in a high-pressure reactor at 60°C for 24 hours, it was immersed and washed 6 times again, and the surface moisture was wiped off to obtain the target product (adhesive antibacterial and antioxidant copper-containing hydrogel).

[0067] Example 2

[0068] 1) A 2 mg / mL gallic acid aqueous solution and a 16 mg / mL copper nitrate aqueous solution were mixed and reacted at a stirring speed of 800 r / min at 37° C. for 2 h, centrifuged at a centrifugal speed of 10000 r / min, washed repeatedly with ultrapure water for 5 times, and then dispersed in ultrapure water to obtain a tannic acid / copper active initiator with a concentration of 4 mg / mL.

[0069] 2) Prepare a 2 mg / mL ammonium persulfate aqueous solution, dissolve acrylamide and acrylic acid therein to make their final concentrations reach 1.8 g / mL and 0.1 g / mL, which is recorded as a gel precursor solution.

[0070] 3) 200 μL of 50 mg / mL double-bond modified gelatin aqueous solution was mixed with 800 μL of gel precursor solution, and then 60 μL of initiator was added, and the prefabricated gel was obtained after waiting at room temperature for 25 minutes.

[0071] 4) The prefabricated gel was immersed and washed 6 times in ultrapure water at room temperature, and then placed in an aqueous solution containing 50 mg / mL dopamine hydrochloride. The solution was adjusted to pH = 10 by adding 1 M sodium hydroxide alkaline solution. After the reaction was closed in an 80°C high-pressure reactor for 12 hours, it was immersed and washed 10 times again, and the surface moisture was wiped off to obtain the target product (adhesive antibacterial and antioxidant copper-containing hydrogel).

[0072] Example 3

[0073] 1) A 6 mg / mL tannic acid aqueous solution and a 32.5 mg / mL copper nitrate aqueous solution were mixed and reacted at 28° C. at a stirring speed of 500 r / min for 30 min, centrifuged at a centrifugal speed of 8000 r / min, washed repeatedly with ultrapure water for 6 times, and then dispersed in ultrapure water to obtain a tannic acid / copper active initiator with a concentration of 5.5 mg / mL.

[0074] 2) Prepare a 1 mg / mL ammonium persulfate aqueous solution, dissolve acrylamide and acrylic acid therein to make their final concentrations reach 1 g / mL and 0.2 g / mL, which is recorded as a gel precursor solution.

[0075] 3) 100 μL of 50 mg / mL double-bond modified gelatin aqueous solution was mixed with 500 μL of gel precursor solution, and then 100 μL of initiator was added, and the prefabricated gel was obtained after waiting for 5 minutes at room temperature.

[0076] 4) The prefabricated gel was immersed and washed 5 times in ultrapure water at room temperature, and then placed in an aqueous solution containing 30 mg / mL dopamine hydrochloride. The solution was adjusted to pH = 10 by adding 1 M sodium hydroxide alkaline solution, and reacted in a closed autoclave at 120° C. for 2 hours. Then, the prefabricated gel was immersed and washed 10 times again, placed in an oven at 60° C., and the surface moisture was dried for 0.5 hours to obtain the target product (adhesive antibacterial and antioxidant copper-containing hydrogel).

[0077] Example 4

[0078] Same as Example 3, except that the concentration of the dopamine hydrochloride aqueous solution in step 4) is 5 mg / mL.

[0079] Comparative Example 1

[0080] Same as Example 3, except that the double-bond modified gelatin aqueous solution is replaced by gelatin aqueous solution.

[0081] Comparative Example 2

[0082] The same as Example 3, except that step 1) is removed, and tannin polyphenol / copper complex is not used as the initiator, but only ammonium persulfate is used as the initiator.

[0083] Comparative Example 3

[0084] Similar to Example 3, instead of using a high-pressure reactor, the prefabricated gel was directly placed in a polytetrafluoroethylene dish and reacted at 120° C. for 2 h.

[0085] Test Example 1

[0086] Figure 1 TEM and element distribution diagram of tannic acid / copper initiator in Example 3; Figure 1 It can be seen that tannic acid and copper ions form an amorphous organometallic complex in the aqueous phase, and the copper element is clearly present and evenly distributed in the substance.

[0087] Figure 2 is the NMR spectrum of the double bond modified gelatin in implementation case 3; Figure 2 It can be seen that obvious double bond characteristic peaks appear at 5.58ppm and 5.34ppm, proving the successful modification of the double bond.

[0088] Figure 3 To prepare the gel in Example 3; Figure 3The successful preparation of the precast gel can be seen in the figure, and due to the presence of tannic acid, the gel presents a uniform yellow-brown color.

[0089] Figure 4 To implement the adhesion test of the prefabricated gel in Case 3, from left to right: 5mL sample bottle, No. 7 battery, 25g weight, 100g weight; Figure 4 It can be seen that the prefabricated gel has good adhesion properties at the glass, plastic and metal interfaces.

[0090] Figure 5 The adhesive antibacterial and antioxidant copper-containing hydrogel in Example 3 (left: before stretching; right: after stretching); Figure 5 It can be seen that dopamine forms a uniform polymer inside and on the surface of the gel, and the gel has good adhesion and tensile properties.

[0091] Figure 6 The antibacterial and antioxidant copper-containing hydrogel in the implementation case 3 is adhered to the surface of the medium; Figure 6 It can be seen that the gel has good adhesion properties at the glass and rubber interfaces; it is not easy to fall off during the peeling process, and the gel has high mechanical strength.

[0092] Figure 7 In the implementation case 3, the antibacterial and antioxidant copper-containing hydrogel with adhesive properties was used to test the anti-E. coli effect, wherein the E. coli culture conditions were: PBS 5.0 buffer solution, 1 mM H 2 O 2 , 37℃, 30min; Left: not co-cultured with gel; Right: co-cultured with gel; Figure 7 It can be seen that the Escherichia coli co-cultured with the gel under acidic conditions cannot survive, while the bacteria not co-cultured with the gel are still active, proving that the gel has a good bactericidal effect on Gram-negative bacteria; and because the cell wall of Escherichia coli is thicker than that of Staphylococcus aureus, it is theoretically shown that the gel also has a good ability to resist Gram-positive bacteria.

[0093] Figure 8 To demonstrate the antioxidant effect of the adherent antibacterial and antioxidant copper-containing hydrogel in Example 3, left 1 to left 3: Characterization of ROS in L929 cells induced by Rosup after co-culture with the gel for 0, 4, and 24 hours, respectively. The stronger the green fluorescence, the more severe the oxidative stress. Figure 8 It can be seen that the gel has a good antioxidant effect and can effectively remove the active oxygen in the cells co-cultured with it.

[0094] Fig. 9 The following are samples of the antibacterial and antioxidant copper-containing hydrogel in Example 3 just prepared (left) and after being stored for one week at 25°C and 55% humidity (middle and right). Fig. 9 It can be seen that the gel has a good water retention effect and has not completely lost water and shriveled. In terms of appearance, there is no obvious difference from the freshly prepared gel and it still has adhesion.

[0095] Fig.10 This is a picture of the prefabricated gel sample prepared in Comparative Example 1. Fig.10 It can be seen that after replacing the double-bonded gelatin with unmodified gelatin, the resulting precast gel is fragile and does not form. This is because the cross-linking effect of the double-bonded gelatin is lost, the cross-linking points are reduced, and the precast gel cannot form a network cross-linking, so the mechanical strength is poor.

[0096] Fig.11 This is the gelation condition in Comparative Example 2 where no tannin polyphenol / copper complex is used as an initiator and only ammonium persulfate is used as an initiator. Fig.11 It can be seen that without the tannin polyphenol / copper complex as an initiator, the solution could not gel within 30 min.

[0097] Fig.12 This is a sample of the antibacterial and antioxidant copper-containing hydrogel prepared in Comparative Example 3. As shown in the figure, compared with the gel obtained by heating in a high-pressure reactor, it can be seen that the dopamine polymerization inside and on the surface of the gel is incomplete, the gel texture is soft, and the mechanical strength is not as good as the colloid mechanical strength obtained after the high-pressure reaction.

[0098] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions and improvements made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims

1. A method for preparing an adherent antibacterial and antioxidant copper-containing hydrogel, characterized in that: The following steps are involved: 1) adding water to tannin polyphenol to prepare a tannin polyphenol aqueous solution, adding water to copper nitrate to prepare a copper nitrate solution, mixing the tannin polyphenol aqueous solution and the copper nitrate solution, centrifuging and washing, and dispersing the obtained tannin polyphenol / copper complex in water to obtain an initiator; 2) adding water to ammonium persulfate to prepare an ammonium persulfate aqueous solution, and then mixing it with an acrylamide solution and acrylic acid to obtain a gel precursor solution; 3) preparing a double-bond modified gelatin aqueous solution, and then mixing it with the gel precursor solution of step 2) and the initiator of step 1) to react to obtain a prefabricated gel; 4) Soaking the prefabricated gel in step 3) in ultrapure water, then placing it in an aqueous solution of dopamine hydrochloride, adjusting the pH of the solution to alkaline, heating to polymerize the dopamine, washing, drying, and wiping off excess water on the surface to obtain an adherent antibacterial and antioxidant copper-containing hydrogel; the heating is performed in a closed high-pressure reactor.

2. The method for preparing the adherent antibacterial and antioxidant copper-containing hydrogel according to claim 1, characterized in that: In step 1), the tannin polyphenol is one or more of tannic acid, catechin, gallic acid and anthocyanin; the mass ratio of the tannin polyphenol to copper nitrate is 1:(5-8).

3. The method for preparing the adherent antibacterial and antioxidant copper-containing hydrogel according to claim 1, characterized in that: In step 2), the concentration of the aqueous ammonium persulfate solution is 0.5-2 mg / mL; the final concentration of acrylamide is 0.5-2.0 g / mL; and the final concentration of acrylic acid is 0.1-5.0 g / mL.

4. The method for preparing the adherent antibacterial and antioxidant copper-containing hydrogel according to claim 1, characterized in that: In step 3), the concentration of the double-bond modified gelatin aqueous solution is 10-100 mg / mL; the concentration of the initiator is 2-10 mg / mL; the reaction temperature is 10-35° C., and the reaction time is 10 s-30 min.

5. The method for preparing the adherent antibacterial and antioxidant copper-containing hydrogel according to claim 1, characterized in that: In step 4), the soaking parameters are: temperature 4-37° C., time 5-10 min, number of times 4-6 times; the concentration of the dopamine hydrochloride aqueous solution is 1-100 mg / mL; the number of washings after the dopamine polymerization is complete is 6-10 times.

6. The method for preparing the adherent antibacterial and antioxidant copper-containing hydrogel according to claim 1, characterized in that: In step 4), the pH is 8-10; the heating temperature is 60-140° C., and the heating time is 2-24 h.

7. An adherent antibacterial and antioxidant copper-containing hydrogel prepared by the preparation method according to any one of claims 1 to 6.

8. Use of the adherent antibacterial and antioxidant copper-containing hydrogel as claimed in claim 7 as an infected wound repair material.

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