Adhesive hydrogel as well as preparation method and application thereof

Abstract

The invention relates to adhesive hydrogel and a preparation method and application thereof, and belongs to the technical field of hydrogel, the adhesive hydrogel comprises a double-network structure formed by interpenetrating a first network and a second network, the first network structure is formed by physical crosslinking of tannic acid and polyvinyl alcohol through multiple hydrogen bonds, and the second network structure is formed by interpenetrating of tannic acid and polyvinyl alcohol through multiple hydrogen bonds. The second network structure is a covalent cross-linked network formed by metacrylic acid ester monomers and sulfanilamide betaine under the action of free radical polymerization; wherein the second network structure is connected with the first network structure through substitution reaction; a rigid brittle first network with high crosslinking density is formed through interpenetration of two networks with different chemical compositions and crosslinking mechanisms, is supported by a high-strength structure and has a synergistic effect with a flexible and high-toughness second network with low crosslinking degree, and high strength and self-repairing capability are combined, so that the self-repairing performance is improved under the action of external stimulation; the rigid first network structure serves as a framework to provide structural support for the hydrogel, and meanwhile the flexible second network structure enhances the toughness of the hydrogel while dissipating energy.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of hydrogel, in particular to an adhesive hydrogel, a preparation method and use thereof. BACKGROUND

[0002] In recent years, the healing of chronic wounds (such as diabetic ulcers, infected wounds) is facing problems such as infection, inflammation, oxidative stress, and imbalance of wet environment, which has brought great threat to the life and health of patients; and traditional wound dressings (such as gauze, sponge) are difficult to dynamically respond to changes in wound microenvironment. Therefore, the development of medical materials with rapid antibacterial hemostatic effect and bacterial infection treatment function is a great challenge and clinical demand in the field of wound healing.

[0003] Medical materials for wound surface still show many deficiencies in treating bacterial infection, antibacterial coagulation, etc., so a new material needs to be prepared for treating excessive bleeding and wound infection. Hydrogel wound dressing is a semi-transparent gel-like dressing made of hydrophilic polymer materials (such as polyvinyl alcohol, polyacrylamide, sodium alginate, etc.). Hydrogel maintains a moist wound environment through high water content and good air permeability, accelerates healing and reduces pain. It is widely used in burn, chronic ulcer, postoperative wound and other scenes. However, the existing hydrogel dressing generally exposes the defect of insufficient adhesion in clinical use, which becomes a key bottleneck restricting its efficacy and safety. Specifically, it is shown that:

[0004] 1. Weak binding force with skin or wound base, easy to shift or fall off during limb movement or dressing change, leading to secondary exposure of wound, mechanical damage and increased risk of infection;

[0005] 2. In a wet environment with more exudate, the interface of traditional hydrogel forms a "synovial layer" due to water infiltration, and the shear strength decreases rapidly, which cannot realize sustained fixation;

[0006] 3. The existing methods of fixing through physical adhesion (such as elastic bandage, medical tape) or chemical adhesive (such as acrylate pressure-sensitive adhesive) not only increase the operation complexity, but also may cause skin allergy, residual glue marks and other problems, and the long-term sealing of adhesive tape may cause the immersion of wound surface.

[0007] The root cause of the above adhesion defects lies in the single design of hydrogel network, the lack of chemical groups capable of forming multiple interfacial interactions (hydrogen bond, hydrophobic, ionic bond, covalent bond) with the stratum corneum, collagen or fibrin of the skin, and the high water content of the network leading to mismatched modulus, which cannot form effective mechanical locking with soft tissue. Therefore, the development of a new type of hydrogel dressing with high wet adhesion and without affecting wound healing has become an urgent need in the field of wound repair materials. SUMMARY

[0008] To overcome some of the problems mentioned in the background above, the present application provides an adhesive hydrogel and its preparation method and use to at least partially solve the above problems.

[0009] According to the technical scheme of the present application, an adhesive hydrogel is provided, comprising a double network structure formed by a first network and a second network penetrating each other, the first network structure being formed by physical cross-linking of tannic acid and polyvinyl alcohol through multiple hydrogen bonds, and the second network structure being formed by free radical polymerization of a methacrylate monomer and a sulfobetaine to form a covalently cross-linked network.

[0010] The second network structure is connected to the first network structure through a substitution reaction.

[0011] Preferably, the raw materials include the following mass percentages:

[0012] 8-12% of polyvinyl alcohol, 2-5% of tannic acid, 10-20% of sulfobetaine, 3-7% of a methacrylate monomer, and the balance of water.

[0013] Preferably, the molecular weight of the polyvinyl alcohol is 12000-31000.

[0014] Preferably, the preparation method of the sulfobetaine comprises the following steps:

[0015] Vacuum dry 3-(dimethylamino) chloropropane hydrochloride for 2 hours, dry 1,2-dichloroethane with 4A molecular sieves for 12 hours, prepare a 50 wt % sodium hydroxide solution, and prepare an ice bath;

[0016] Add 3-(dimethylamino) chloropropane hydrochloride and 1,2-dichloroethane into a three-necked flask, slowly add the 50 wt % sodium hydroxide solution dropwise in an ice bath environment, control the pH to be 11-12, continue stirring for 30 minutes after the dropwise addition is completed; then perform liquid-liquid separation, wash the organic phase with saturated sodium chloride, and then dry it with anhydrous sodium sulfate to obtain a free amine solution;

[0017] Dissolve 1,3-propanesultone in 1,2-dichloroethane, and add the free amine solution dropwise into the 1,3-propanesultone solution within 30 minutes in an ice bath environment, keep the temperature ≤10℃, and after the dropwise addition is completed, warm it up to 25℃, react for 4 hours until the iodine cylinder color PSL spot disappears;

[0018] After evaporating 1,2-dichloroethane under reduced pressure, dissolve the residue in anhydrous ethanol, pass dry hydrogen chloride gas for 15 minutes under ice bath to precipitate white solids, filter the solids, wash them twice with ice ethanol, and then dry them at 60℃ under vacuum for 2 hours to obtain sulfobetaine.

[0019] Preferably, the methacrylate monomers include one or more of methyl methacrylate, ethyl methacrylate, butyl methacrylate and glycidyl methacrylate.

[0020] In another aspect, the present application also provides a method for preparing an adhesive hydrogel, comprising the following steps:

[0021] S1. mixing and stirring the tannic acid solution and the polyvinyl alcohol solution until completely dissolved to obtain a first network pre-polymer solution;

[0022] S2. adding the methacrylic monomer and the sulfobetaine into the first network pre-polymer solution respectively and stirring until uniform to obtain a mixed solution;

[0023] S3. placing the mixed solution in a mold and performing a freeze-thaw cycle to obtain the adhesive hydrogel.

[0024] Further, the tannic acid solution and the polyvinyl alcohol solution are prepared by dissolving tannic acid and polyvinyl alcohol in water respectively, and the second network solution is prepared by dissolving the methacrylic monomer and the sulfobetaine in water;

[0025] After heating the polyvinyl alcohol solution to boiling, the tannic acid solution is added and stirred for 20-30 min until completely dissolved.

[0026] Further, the second network solution is added to the first network pre-polymer solution and stirred until uniform, and then nitrogen is introduced to remove oxygen for 15-20 min.

[0027] Further, the freeze-thaw cycle comprises the following steps:

[0028] The mixed solution is placed in a mold, and then the mold is placed in -30℃--20℃ for freezing for 2-4 h, and then the mold is taken out and placed in a room temperature environment for thawing for 2-4 h, and the freeze-thaw cycle is repeated for 1-3 times to obtain the adhesive hydrogel.

[0029] In another aspect, the present application also provides an application of the adhesive hydrogel, and the adhesive hydrogel is applied in the field of gel dressings.

[0030] Compared with the prior art, the present application has the following beneficial effects:

[0031] The present application is formed by two networks with different chemical composition and crosslinking mechanism. The rigid and brittle first network with high crosslinking density is supported by high strength structure, and cooperates with the flexible and high toughness second network with low crosslinking density, the two network structures are independent and interpenetrated, the rigid network structure is formed by covalent bond first, and then the flexible network is formed by introducing hydrogen bond, ionic bond or hydrophobic interaction, which combines high strength and self-repairing ability. Under the action of external stimulus, the rigid first network structure provides structural support for the hydrogel as a skeleton, and at the same time the flexible second network structure enhances the toughness of the hydrogel while dissipating energy.

[0032] The double network structure formed by the combination of tannic acid, polyvinyl alcohol polymer and zwitterions in the present application can not only improve the toughness and strength of the hydrogel, but also improve the adhesive strength of the hydrogel due to the interpenetrating structure of the double network, and the adhesive hydrogel also has antibacterial and hemostatic effects, and can be used as a wound dressing. BRIEF DESCRIPTION OF DRAWINGS

[0033] Figure 1 The infrared spectrum of the hydrogel prepared in the embodiment of the present application is shown in the figure;

[0034] Figure 2 The scanning electron microscope image of the hydrogel prepared in the embodiment of the present application is shown in the figure;

[0035] Figure 3 The rheological property test figure of the hydrogel prepared in the embodiment of the present application is shown in the figure;

[0036] Figure 4 The adhesion test figure of the hydrogel prepared in the embodiment of the present application is shown in the figure;

[0037] Figure 5 The bacteriostatic effect figure of the hydrogel prepared in the embodiment of the present application is shown in the figure;

[0038] Figure 6 The hemostatic effect figure of the hydrogel prepared in the embodiment of the present application is shown in the figure. DETAILED DESCRIPTION

[0039] The technical solutions in the embodiments will be described clearly and completely below with reference to the drawings in the embodiments of the present application. Obviously, the described embodiments are only part of the embodiments of the present application, not all the embodiments. Based on the embodiments, all other embodiments obtained by those skilled in the art without creative labor are within the scope of protection.

[0040] The embodiment of the present application provides an adherent hydrogel, which comprises a double network structure formed by a first network and a second network penetrating each other, the first network structure is formed by tannin and polyvinyl alcohol by multiple hydrogen bond physical crosslinking, and the second network structure is formed by a methacrylate monomer and a sulfobetaine by free radical polymerization to form a covalently crosslinked network.

[0041] The second network structure is connected with the first network structure through a substitution reaction.

[0042] In a further embodiment of the present application, the raw materials include the following mass percentages:

[0043] 8-12% of polyvinyl alcohol, 2-5% of tannin, 10-20% of sulfobetaine, 3-7% of a methacrylate monomer, and the balance of water.

[0044] In a further embodiment of the present application, the molecular weight of the polyvinyl alcohol is 12000-31000.

[0045] In a further embodiment of the present application, the preparation method of the sulfobetaine comprises the following steps:

[0046] 3-(dimethylamino) chloropropane hydrochloride is vacuum dried for 2 hours, 1,2-dichloroethane is dried with 4A molecular sieves for 12 hours, a 50 wt % sodium hydroxide solution is prepared, and an ice bath is prepared;

[0047] 3-(dimethylamino) chloropropane hydrochloride and 1,2-dichloroethane are added to a three-necked flask, and a 50 wt % sodium hydroxide solution is slowly added dropwise in an ice bath environment, the pH is controlled to be 11-12, and stirring is continued for 30 minutes after the dropwise addition is completed; then, liquid separation is performed, the organic phase is washed with saturated sodium chloride, and then dried with anhydrous sodium sulfate to obtain a free amine solution;

[0048] 1,3-propane sultone is dissolved in 1,2-dichloroethane, the free amine solution is added dropwise into the 1,3-propane sultone solution in an ice bath environment within 30 minutes, the temperature is kept ≤10℃, the temperature is raised to 25℃ after the dropwise addition is completed, and the reaction is stopped after 4 hours when the iodine cylinder color PSL spot disappears;

[0049] After 1,2-dichloroethane is distilled off under reduced pressure, the residue is dissolved in anhydrous ethanol, white solid is precipitated by introducing dry hydrogen chloride gas for 15 minutes under ice bath, the solid is obtained after filtration, washed twice with ice ethanol, and then dried at 60℃ under vacuum for 2 hours to obtain sulfobetaine.

[0050] In a further embodiment of the present application, the methacrylate monomer comprises one or more of methyl methacrylate, ethyl methacrylate, butyl methacrylate and glycidyl methacrylate.

[0051] It should be noted that single tannic acid and polyvinyl alcohol polymer form a single network hydrogel, which is strong in rigid brittleness and poor in adhesion, and is generally used for brittle applications, and the present application is formed by interpenetration of two networks with different chemical compositions and crosslinking mechanisms. The rigid and brittle first network with high crosslinking density is supported by high strength structure, and cooperates with the flexible and high toughness second network with low crosslinking degree, the two network structures are independent and interpenetrated, first form a rigid network structure through covalent bond, and then introduce hydrogen bond, ionic bond or hydrophobic interaction to form a flexible network, which combines high strength and self-repairing ability. Under the action of external stimulus, the rigid first network structure provides structural support for the hydrogel as a skeleton, and at the same time the flexible second network structure enhances the toughness of the hydrogel while dissipating energy.

[0052] On the other hand, the present application also provides a preparation method of the adhesive hydrogel, comprising the following steps:

[0053] S1. mixing and stirring tannic acid solution and polyvinyl alcohol solution to completely dissolve, to obtain a first network pre-polymer solution;

[0054] S2. adding methacrylic acid lipid monomer and sulfobetaine into the first network pre-polymer solution respectively and stirring uniformly to obtain a mixed solution;

[0055] S3. placing the mixed solution in a mold, and obtaining the adhesive hydrogel through freeze-thaw cycle.

[0056] In a further embodiment of the present application, tannic acid and polyvinyl alcohol are dissolved in water to prepare tannic acid solution and polyvinyl alcohol solution, and methacrylic acid lipid monomer and sulfobetaine are dissolved in water to prepare a second network solution;

[0057] After the polyvinyl alcohol solution is heated to boiling, the tannic acid solution is added and stirred for 20-30 min to completely dissolve.

[0058] In a further embodiment of the present application, the second network solution is added to the first network pre-polymer solution and stirred uniformly, and then nitrogen is introduced to remove oxygen for 15-20 min.

[0059] In a further embodiment of the present application, the freeze-thaw cycle comprises the following steps:

[0060] The mixed solution is placed in a mold, and then the mold is placed at-30℃ to-20℃ for freezing for 2-4 h, and then the mold is taken out and placed at room temperature for thawing for 2-4 h, and the freeze-thaw cycle is repeated for 1-3 times to obtain the adhesive hydrogel.

[0061] It is to be noted that the catechol / pyrogallol groups in TA molecules can not only form a large number of hydrogen bonds with the hydroxyl groups on PVA, but more importantly, these phenolic groups can form covalent / non-covalent interactions with the amino, thiol and other groups on the tissue surface, providing strong wet-state adhesion. This physical network can effectively dissipate energy through the reversible breaking and recombination of hydrogen bonds when stressed, endowing the hydrogel with toughness and self-healing properties.

[0062] The DCAPS unit, i.e. the sulfobetaine unit, produces strong hydration through its zwitterionic structure, forming a "hydration layer" that effectively resists the non-specific adsorption of proteins, bacteria and cells, providing excellent anti-fouling performance. The homopolymer (poly-GMA) segment of GMA, i.e. the methacrylic acid ester monomer, provides rigid support, enhancing the overall modulus and strength of the hydrogel.

[0063] The phenolic hydroxyl groups on the TA molecules in the first network undergo ring-opening reaction with the epoxy groups provided by the GMA units in the second network and substitution reaction with the chlorines on the sulfobetaine, forming stable covalent bonds, greatly enhancing the interfacial stability, avoiding phase separation and ensuring efficient stress transmission between the two networks, thereby synergistically improving the overall performance of the hydrogel.

[0064] On the other hand, the present application also provides an application of the adhesive hydrogel, and the adhesive hydrogel is applied in the field of gel dressings.

[0065] The raw materials used in the following examples and comparative examples are as follows:

[0066] Polyvinyl alcohol was purchased from Shanghai Aldrin Biochemical Technology Co., Ltd., with the brand PVA-1799 and a molecular weight of 195000.

[0067] Tannic acid was purchased from Shanghai Aldrin Biochemical Technology Co., Ltd.

[0068] (Dimethylamino) chloropropane hydrochloride was purchased from Shanghai Aldrin Biochemical Technology Co., Ltd.

[0069] 1,3-propanesultone was purchased from Shanghai Aldrin Biochemical Technology Co., Ltd.

[0070] The preparation method of sulfobetaine is

[0071] Pre-treatment of raw materials: 3-(dimethylamino) chloropropane hydrochloride (DMAPCl·HCl) 100 mmol (15.8 g) was vacuum dried for 2 h (40℃, ≤10 mbar). 1,2-dichloroethane (DCE) 150 mL was dried with 4 Å molecular sieves for 12 h. NaOH: prepared into a 50 wt % sodium hydroxide solution and kept in an ice bath.

[0072] Free amine: In a three-neck flask, add DMAPCl-HCl and 50 mL DCE, ice bath, slowly add 50wt% NaOH 5.0 mL, control pH 11-12, continue stirring for 30 min after dropping. Separate, the organic phase is washed with saturated NaCl 20 mL, then dried with anhydrous Na2SO4, to get free amine DCE solution (about 50 mL).

[0073] Sulfonated ring opening: 1,3-propane sulfonate lactone 12.2 g is dissolved in 50 mL DCE, ice bath. The free amine DCE solution of the previous step is added dropwise to the 1,3-propane sulfonate lactone solution within 30 min, the temperature is kept ≤10℃, after dropping, the temperature is raised to 25℃, and the reaction is carried out for 4 h until the PSL spot disappears by TLC (iodine coloration) to stop.

[0074] Salting and purification: after the reaction, the DCE is evaporated under reduced pressure (40℃, vacuum degree ≤20 mbar). The residue is dissolved in 50 mL anhydrous ethanol, and dry HCl gas is introduced for 15 min under ice bath. White solid is precipitated. The solid is filtered, washed twice with ice ethanol, and then vacuum dried at 60℃ / 2 h to obtain DCAPS-HCl white crystals.

[0075] Example 1

[0076] Prepare a tannic acid solution and a polyvinyl alcohol solution by dissolving 4% by mass of tannic acid and 10% by mass of polyvinyl alcohol in water, respectively, and prepare a second network solution by dissolving 5% by mass of a methacrylic monomer and 10% by mass of sulfobetaine in water,

[0077] After heating the polyvinyl alcohol solution to boiling, the tannic acid solution is added and stirred for 20-30 min to completely dissolve to obtain a first network pre-polymer solution.

[0078] The methacrylic monomer and sulfobetaine are added to the first network pre-polymer solution respectively and stirred uniformly, and then nitrogen is introduced to remove oxygen for 15-20 min to obtain a mixed solution.

[0079] The mixed solution is placed in a mold, and the mixed solution is placed in the mold, and then the mold is placed in a freezer at -30℃ for 4 h, and then the mold is taken out and placed in a room temperature environment for thawing for 3 h. After 2 cycles of freezing and thawing, an adhesive hydrogel is obtained, and the adhesive hydrogel is white and has a luster.

[0080] Example 2

[0081] A tannic acid solution and a polyvinyl alcohol solution were prepared by dissolving 4wt% tannic acid and 10wt% polyvinyl alcohol in water respectively, a second network solution was prepared by dissolving 5wt% methacrylic monomer and 20wt% sulfobetaine in water,

[0082] The tannic acid solution was added to the polyvinyl alcohol solution after the polyvinyl alcohol solution was heated to boiling, and stirring was performed for 20-30min to completely dissolve the tannic acid solution to obtain a first network pre-polymer solution.

[0083] The methacrylic monomer and the sulfobetaine were added to the first network pre-polymer solution respectively, and stirring was performed until the methacrylic monomer and the sulfobetaine were uniformly mixed, and then nitrogen was introduced to remove oxygen for 15-20min to obtain a mixed solution.

[0084] The mixed solution was placed in a mold, and the mixed solution was placed in the mold, and then the mold was placed in a freezer at -30℃ for 4h, and then the mold was taken out and placed in a room temperature environment for thawing for 3h, and the freezing and thawing cycle was repeated twice to obtain an adhesive hydrogel, and the adhesive hydrogel was obtained, and the adhesive hydrogel was white and had a luster.

[0085] Comparative Example

[0086] The comparative example was a comparative example of Example 1, and the difference between the comparative example and Example 1 was that 10wt% sulfobetaine aqueous solution was not added to the mixed solution, and the rest was the same as Example 1.

[0087] The adhesive hydrogels prepared in Example 1, Example 2 and Comparative Example 1 were subjected to infrared detection, and the infrared spectrum was as shown in Figure 1 According to the infrared spectrum, it can be seen that the absorption peaks at wave numbers of 3300, 2100 cm -1 , respectively, are produced by the stretching vibration of the O-H bond and the C-H bond of the PVA molecule, there is an absorption peak at 1630 cm -1 , which is caused by the stretching vibration of C=O in the TA molecule, there is an absorption peak at 1400 cm -1 , which is attributed to the stretching vibration of C=C on the aromatic ring in the TA molecule, and there is an absorption peak near 570 cm -1 , which is a characteristic peak vibration of the ortho-substituted benzene ring in the TA molecule. The infrared spectrum of the composite hydrogel shows that the wavelength moves towards a low wave number and the intensity decreases, which indicates that the introduction of DCAPS promotes the formation of intermolecular hydrogen bonds, and indicates that the PVA / TA / DCAPS hydrogel is constructed by a three-dimensional network structure through physical crosslinking.

[0088] As Figure 2As shown in Fig. 1 (a), the PVA / TA hydrogel prepared by freeze-thawing method presents a honeycomb-like network structure, and the morphology and size of the pores present non-uniform changes. With the increase of the concentration of the added DCAPS reagent, the microstructure of the PVA / TA / DCAPS hydrogel changes: when 10% DCAPS is added, as shown in Fig. 1 (b), part of the pores is filled, resulting in a decrease in the size of the pores; when the concentration of DCAPS increases to 20%, as shown in Fig. 1 (c), most of the pores are effectively filled, making the originally relatively loose network structure obviously compact, indicating that the addition of DCAPS can adjust the pore structure of the hydrogel. Figure 2 As shown in Fig. 1 (b), part of the pores is filled, resulting in a decrease in the size of the pores; when the concentration of DCAPS increases to 20%, as shown in Fig. 1 (c), most of the pores are effectively filled, making the originally relatively loose network structure obviously compact, indicating that the addition of DCAPS can adjust the pore structure of the hydrogel. Figure 2 As shown in Fig. 1 (c), most of the pores are effectively filled, making the originally relatively loose network structure obviously compact, indicating that the addition of DCAPS can adjust the pore structure of the hydrogel.

[0089] Figure 4 The adhesion effects of the PVA / TA and PVA / TA / DCAPS hydrogels were compared. The experimental results show that the PVA / TA hydrogel has certain adhesion ability to pigskin and wood board, but the interface bonding is not tight, there are gaps and it is easy to fall off. As shown in Fig. 2 (a), the adhesion effect of the hydrogel on the plastic ruler is poor, there are obvious signs of falling off, and it starts to fall off on the surface of the pigskin within 10 s. The PVA / TA / DCAPS composite hydrogel shows significantly improved adhesion. Figure 4

[0090] The PVA / TA / DCAPS hydrogels prepared in Example 1 and Example 2 and the PVA / TA hydrogel prepared in Comparative Example 1 were subjected to scanning electron microscope analysis, and the scanning electron microscope images are shown in Fig. 3. Figure 2 As shown in Fig. 3 (a), the PVA / TA hydrogel prepared by freeze-thawing method presents a honeycomb-like network structure, and the morphology and size of the pores present non-uniform changes. With the increase of the concentration of the added DCAPS reagent, the microstructure of the PVA / TA / DCAPS hydrogel changes: when 10% DCAPS is added, as shown in Fig. 3 (b), part of the pores is filled, resulting in a decrease in the size of the pores; when the concentration of DCAPS increases to 20%, as shown in Fig. 3 (c), most of the pores are effectively filled, making the originally relatively loose network structure obviously compact, indicating that the addition of DCAPS can adjust the pore structure of the hydrogel. Figure 2 As shown in Fig. 3 (b), part of the pores is filled, resulting in a decrease in the size of the pores; when the concentration of DCAPS increases to 20%, as shown in Fig. 3 (c), most of the pores are effectively filled, making the originally relatively loose network structure obviously compact, indicating that the addition of DCAPS can adjust the pore structure of the hydrogel. Figure 2 As shown in Fig. 3 (c), most of the pores are effectively filled, making the originally relatively loose network structure obviously compact, indicating that the addition of DCAPS can adjust the pore structure of the hydrogel. Figure 2

[0091] The PVA / TA / DCAPS hydrogels prepared in Example 1 and Example 2 and the PVA / TA hydrogel prepared in Comparative Example 1 were subjected to rheological test, adhesion performance test, antibacterial test and hemostatic performance test.

[0092] 1. The PVA / TA / DCAPS hydrogels prepared in Example 1 and Example 2 and the PVA / TA hydrogel prepared in Comparative Example 1 were subjected to rheological test, and the results are shown in Table 1. Figure 3 ​​As shown, they are respectively Figure 3 (b) Figure 3 (c) Figure 3 (a). For example Figure 3 As shown, it is evident that G' is significantly higher than G″ when 20% DCAPS is added, indicating a stronger interaction between the PVA / TA / DCAPS hydrogels. This allows the material to form a stable elastic gel network structure, effectively storing energy rather than dissipating it. A higher G' signifies a tighter cross-linked network, providing structural strength and shape retention. The changes in G' and G″ over time at different frequencies, with G' decreasing and G″ increasing, suggest that the introduction of DCAPS may affect the gel's flexibility or rigidity through dynamic reversible cross-linking and hydrogen bonding-mediated viscoelasticity regulation.

[0093] 2. The adhesion properties of the PVA / TA / DCAPS hydrogel prepared in Example 1 and the PVA / TA hydrogel prepared in Comparative Example 1 were tested. The test methods are as follows:

[0094] Take one piece each of the PVA / TA / DCAPS hydrogel prepared in Example 1 and the PVA / TA hydrogel prepared in Comparative Example 1 from the mold, scrape off the grease from the pigskin surface, and cut them into 5 cm × 4 cm × 5 mm samples. Place the hydrogel on the treated pigskin surface, ensuring full contact between the hydrogel and the pigskin, observe the interfacial adhesion, record the adhesion time, and take photos. Repeat this process with materials such as wood chips and plastic rulers, comparing and observing the adhesion ability while taking photos. Figure 4 As shown, they are respectively Figure 4 (a) and Figure 4 (b).

[0095] like Figure 4 As shown in (b), although the PVA / TA hydrogel has a certain adhesion to pigskin and wood, the interface bonding is not tight, and gaps exist, making it easy to fall off. The adhesion of this hydrogel on the plastic ruler is poor, with obvious signs of detachment, and it only lasts for 10 seconds on the pigskin surface before starting to detach. Figure 4 As shown in (a), the PVA / TA / DCAPS hydrogel exhibits significantly improved adhesion, and can adhere tightly to the surfaces of various materials such as pigskin, wood, and plastic rulers, maintaining adhesion for 1 minute before detaching. With strong adhesion, the PVA / TA / DCAPS hydrogel can firmly adhere to the surfaces of various materials, and has the potential for application in different application scenarios.

[0096] 3. The antibacterial properties of the PVA / TA / DCAPS hydrogels prepared in Examples 1 and 2 and the PVA / TA hydrogel prepared in Comparative Example 1 were tested using the following methods:

[0097] Plate coating method: the frozen gel was cut into a disc-shaped sample with d = 6 mm, h = 1 mm, and PVA / TA / DCAPS hydrogel and PVA / TA hydrogel were respectively laid in the middle of the incubated colony culture dish, and E. coli and S. aureus were respectively selected as the bacteria, and incubated at 37℃ for 24 h, and the size of the inhibition zone was recorded by taking pictures, as shown in Figure 5

[0098] Sample A is PVA / TA hydrogel, sample B is PVA / TA / DCAPS (10%) hydrogel, sample C is PVA / TA / DCAPS (20%) hydrogel, and control is the control sample. When the skin is damaged, the wound is exposed to the air, which can cause the wound to be infected with bacteria or viruses, and the main bacteria causing the wound infection are S. aureus and E. coli. By Figure 5 It can be seen that the hydrogel has the effect of inhibiting the growth of S. aureus and E. coli, and can be used for wound dressing.

[0099] 4. Hemostatic performance test

[0100] The hemostatic effect of PTD hydrogel was tested by mouse tail cutting experiment. As known from Figure 6 Compared with the blank group, the sample group using PTD hydrogel as wound hemostatic aid has significantly improved hemostatic speed. Because PTD hydrogel has adhesion, it can not only physically isolate but also continuously press the wound. PTD hydrogel also has high water absorption, which can quickly absorb the moisture in the blood plasma, increase the viscosity of the blood, and quickly gather platelets and coagulation factors, thereby achieving the effect of rapid hemostasis.

[0101] The above only describes the preferred embodiments of the present application and is not intended to limit the present application. For those skilled in the art, the present application can have various modifications and changes. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present application shall be included in the protection scope of the present application.​

Claims

1. An adhesive hydrogel, characterized in that, It includes a dual-network structure formed by the interconnection of a first network and a second network. The first network structure is formed by physical cross-linking of tannic acid and polyvinyl alcohol through multiple hydrogen bonds, and the second network structure is formed by covalently cross-linking of methacrylate monomers and sulfabetaine through free radical polymerization. The second network structure is connected to the first network structure through a substitution reaction.

2. The adhesive hydrogel according to claim 1, characterized in that, Including the following percentages by weight of raw materials: 8-12% polyvinyl alcohol, 2-5% tannic acid, 10-20% sulfabetaine, 3-7% methacrylate monomers and the balance water.

3. The adhesive hydrogel according to claim 1, characterized in that, The molecular weight of the polyvinyl alcohol is 12,000 to 31,000.

4. The adhesive hydrogel according to claim 1, characterized in that, The preparation method of the sulfabeline includes the following steps: 3-(dimethylamino)chloropropane hydrochloride was dried under vacuum for 2 hours, and 1,2-dichloroethane was dried using a 4A molecular sieve for 12 hours. A 50 wt% sodium hydroxide solution was prepared and kept in an ice bath for later use. Add 3-(dimethylamino)chloropropane hydrochloride and 1,2-dichloroethane to a three-necked flask, and slowly add 50 wt% sodium hydroxide solution dropwise under ice bath conditions, controlling the pH to 11–12. After the addition is complete, continue stirring for 30 min. Then, separate the liquid and liquid phases, wash the organic phase with saturated sodium chloride, and then dry it with anhydrous sodium sulfate to obtain a free amine solution. Dissolve 1,3-propanesulfonic acid lactone in 1,2-dichloroethane. Add the free amine solution dropwise to the 1,3-propanesulfonic acid lactone solution over 30 min in an ice bath, keeping the temperature ≤10℃. After the addition is complete, raise the temperature to 25℃ and react for 4 h until the PSL spots in the iodine tank disappear. After removing 1,2-dichloroethane by vacuum distillation, the residue was dissolved in anhydrous ethanol. Dry hydrogen chloride gas was passed through the solution in an ice bath for 15 min to precipitate a white solid. The solid was filtered and washed twice with ice-cold ethanol. Then it was dried under vacuum at 60 °C for 2 h to obtain sulfabetaine.

5. The adhesive hydrogel according to claim 1, characterized in that, The methacrylate monomers include one or more of methyl methacrylate, ethyl methacrylate, butyl methacrylate, and glycidyl methacrylate.

6. A method for preparing an adhesive hydrogel according to any one of claims 1-5, characterized in that, Includes the following steps: S1. Mix and stir the tannic acid solution and polyvinyl alcohol solution until completely dissolved to obtain the first network prepolymer solution; S2. Add methacrylate monomers and sulfabetaine to the first network prepolymer solution and stir until homogeneous to obtain a mixed solution; S3. Place the mixed solution in a mold and perform a freeze-thaw cycle to obtain the adhesive hydrogel.

7. The method for preparing the adhesive hydrogel according to claim 6, characterized in that, Tannic acid and polyvinyl alcohol were dissolved in water to prepare tannic acid solution and polyvinyl alcohol solution, respectively. Methacrylate monomers and sulfabetaine were dissolved in water to prepare a second network solution. Heat the polyvinyl alcohol solution to boiling, then add the tannic acid solution and stir for 20-30 minutes until completely dissolved.

8. The method for preparing the adhesive hydrogel according to claim 7, characterized in that, After adding the second network solution to the first network prepolymer solution and stirring until homogeneous, nitrogen gas is introduced to remove oxygen for 15-20 minutes.

9. The method for preparing the adhesive hydrogel according to claim 6, characterized in that, The freeze-thaw cycle includes the following steps: The mixed solution is placed in a mold, and then the mold is frozen at -30℃ to -20℃ for 2-4 hours. Then the mold is taken out and thawed at room temperature for 2-4 hours. This freeze-thaw cycle is repeated 1-3 times to obtain the adhesive hydrogel.

10. The use of an adhesive hydrogel, characterized in that, The application of the adhesive hydrogel according to any one of claims 1-5 in the field of gel dressings.

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