PH response type composite hydrogel dressing, preparation method and application

Abstract

The invention provides a pH response type composite hydrogel dressing as well as a preparation method and application thereof, and belongs to the technical field of medical materials. According to the pH response type composite hydrogel dressing, gel formed by crosslinking glycyrrhetinic acid and ovalbumin amyloid fibrils is used as a carrier, and a zinc ion modified metal organic framework material is loaded on the carrier. Functional groups such as carboxyl and hydroxyl of glycyrrhetinic acid are combined with ovalbumin amyloid fibrils through hydrogen bonds and electrostatic interaction to form a hydrogel carrier, and then a zinc ion modified metal organic framework material is loaded on the hydrogel carrier to obtain the composite hydrogel dressing. The hydrogel has antibacterial and anti-biofilm effects on escherichia coli and staphylococcus aureus, has good biocompatibility and mechanical properties, has pH responsiveness, and can realize programmed control to actively remove bacteria.

Description

Technical Field

[0001] This invention belongs to the field of medical materials technology, specifically relating to a pH-responsive composite hydrogel dressing, its preparation method, and its application. Background Technology

[0002] The skin is the largest organ in the human body and a vital protective barrier. Skin injuries, being the most common form of trauma to organs, undergo a complex healing process. During wound repair, damaged skin tissue may become infected with bacteria, potentially preventing healing in severe cases. Bacterial infections not only cause local inflammation and tissue damage but can also trigger systemic infections. Although the widespread use of antibiotics has been remarkably effective in controlling bacterial infections, antibiotic resistance remains a growing problem, primarily due to the formation of biofilms by bacteria within the host. This biofilm structure significantly reduces the bacteria's sensitivity to antibiotics, increasing the difficulty of treatment.

[0003] In recent years, the application of biocompatible hydrogels in wound healing has received increasing attention. Hydrogels possess a three-dimensional network structure, excellent moisturizing properties, and the ability to absorb wound exudate, promoting the diffusion of loaded substances and showing broad application prospects in the biomedical field. Furthermore, loading functional nanomedicines into hydrogels for wound healing can not only overcome the problems of rapid drug release and low fixation efficiency at the wound site but also reshape the wound microenvironment. By adhering hydrogels to bacterially infected wounds, sustained drug release and prolonged retention on the wound surface can be achieved, reducing potential off-target side effects, improving treatment efficacy, and accelerating wound repair. However, their poor mechanical properties mean that even simple movement at the wound site can lead to dressing tearing or damage, and their antibacterial properties are limited. To overcome these shortcomings, the development of composite hydrogels has become an important research direction.

[0004] Introducing functionalized nanomaterials into hydrogel networks can significantly improve the mechanical strength of hydrogels, and combining nano-antibacterial agents with hydrogels can enhance their antibacterial properties. For example, invention patent CN120173149A discloses an MXene-based ammonium glycyrrhizate / konjac gum / borax self-healing hydrogel and its preparation method. First, Ti3AlC2 is etched using concentrated hydrochloric acid and lithium fluoride, followed by multiple centrifugation washing, ultrasonication, and vacuum drying to obtain MXene nanosheets. An ammonium glycyrrhizate and konjac gum are used to prepare a hydrosol, and the MXene nanosheets are dispersed in this sol to obtain a dispersed MXene nanosheet sol. Then, an aqueous solution of borax is added to the dispersed MXene nanosheet sol, stirred, and ultrasonically dispersed. The mixture is then heated to the point of boiling, then heating is stopped, and the mixture is left to crosslink at room temperature to obtain the MXene-based self-healing hydrogel.

[0005] Therefore, the development of composite hydrogels can not only improve the performance of traditional hydrogel dressings, but also provide a more effective solution for the treatment of bacterial infections. Summary of the Invention

[0006] To address the aforementioned problems in the prior art, this invention provides a pH-responsive composite hydrogel dressing, its preparation method, and its application. The dressing uses a metal-organic framework material self-assembled from zinc ions and organic ligands as its functional core, exhibiting antibacterial and anti-biofilm effects against bacteria, and also possessing the advantage of being pH-responsive. Glycyrrhetinic acid itself has antibacterial properties, and the hydrogel formed by cross-linking it with ovalbumin amyloid fibrils and loading it with ZIF-8 exhibits excellent mechanical properties and dual antibacterial functions.

[0007] This invention provides a pH-responsive composite hydrogel dressing, wherein the pH-responsive composite hydrogel dressing uses a gel formed by cross-linking glycyrrhetinic acid and ovalbumin amyloid fibrils as a carrier, and the carrier is loaded with a zinc ion-modified metal-organic framework material.

[0008] This invention utilizes a cross-linking reaction between the carboxyl and hydroxyl groups of glycyrrhetinic acid and the amino and carboxyl groups of ovalbumin amyloid fibrils through hydrogen bonding and electrostatic interactions to obtain a gel carrier. Glycyrrhetinic acid itself has excellent antibacterial properties, and the gel formed by cross-linking with ovalbumin amyloid fibrils significantly improves mechanical properties and antibacterial activity. At the same time, zinc ion-modified metal-organic framework materials have significant pH response and excellent antibacterial and anti-biofilm properties. When loaded onto the gel carrier, a pH-responsive composite hydrogel dressing is obtained, which can effectively solve the problems of poor mechanical properties and limited antibacterial activity of existing hydrogels used for bacterial infections.

[0009] Preferably, the zinc ion-modified metal-organic framework material is ZIF-8, ZIF-7, or ZIF-90.

[0010] The zinc ion-modified metal-organic framework materials mentioned above can release Zn 2+ It generates reactive oxygen species (ROS) and releases bactericidal components in a pH-responsive manner.

[0011] More preferably, the zinc ion-modified metal-organic framework material is ZIF-8.

[0012] Preferably, the mass ratio of glycyrrhetinic acid to ovalbumin amyloid fibrils is 0.1 to 1:1.

[0013] Preferably, the mass ratio of glycyrrhetinic acid to zinc ion-modified metal-organic framework material is 0.1 to 1:5.

[0014] This invention also provides a method for preparing a pH-responsive composite hydrogel dressing, comprising the following steps: Step 1: Provide zinc ion-modified metal-organic framework materials; Step 2: Mix ovalbumin with deionized water to obtain an ovalbumin solution. After hydration, heat and stir under acidic conditions to obtain ovalbumin amyloid fibrils. Mix ovalbumin amyloid fibrils with the first buffer solution and adjust the pH to obtain an ovalbumin amyloid fibrils solution. Step 3: Dissolve glycyrrhetinic acid in the second buffer solution to obtain a glycyrrhetinic acid solution, and mix the glycyrrhetinic acid solution with an ovalbumin amyloid fibrils solution to obtain a mixed solution; Step 4: Disperse the zinc ion-modified metal-organic framework material from Step 1 in the mixed solution, and heat and stir to form a pH-responsive composite hydrogel dressing.

[0015] Preferably, in step 1, the preparation method of zinc ion modified metal-organic framework material includes: dissolving zinc source and organic ligand in solvent to obtain first precursor and second precursor respectively; mixing first precursor and second precursor; reflux reaction for 24 h and centrifuging; and drying the centrifuged product to obtain zinc ion modified metal-organic framework material.

[0016] Preferably, the zinc source is at least one of zinc acetate, zinc nitrate, and zinc sulfate.

[0017] More preferably, the zinc source is zinc acetate.

[0018] Preferably, the organic ligand is at least one of dimethylimidazole, benzimidazole, and imidazole-2-carboxaldehyde.

[0019] More preferably, the organic ligand is dimethylimidazole.

[0020] Preferably, the solvent is methanol.

[0021] Preferably, the molar ratio of the first precursor to the second precursor is 1:1 to 8.

[0022] More preferably, the molar ratio of the first precursor to the second precursor is 1:2 to 4.

[0023] More preferably, the centrifugation speed is 8000~10000 r / min.

[0024] More preferably, the drying temperature is 60~80 ℃ and the drying time is 6~24 h.

[0025] Preferably, in step 2, the concentration of the ovalbumin solution is 5-10 wt%.

[0026] Preferably, the ovalbumin solution hydration in step 2 is obtained by dialyzing the ovalbumin solution in distilled water at 4-25°C for 48-72 h and then freeze-drying it.

[0027] Preferably, the acidic condition in step 2 is achieved by adjusting the pH to 2.0 using hydrochloric acid; The heating temperature under acidic conditions was 85℃, and the heating time was 12 h.

[0028] Preferably, the first buffer in step 2 is a 0.5 M Bis-Tris buffer at pH 6.8.

[0029] Preferably, in step 2, the pH of the blend solution is 2.0-5.8.

[0030] More preferably, the concentration of the ovalbumin amyloid fibrils solution in step 2 is 2-6 wt%.

[0031] Preferably, the second buffer in step 3 is a 10 mM Bis-Tris buffer at pH 5.8.

[0032] Preferably, the concentration of glycyrrhetinic acid solution in step 3 is 0.2-0.4 wt%.

[0033] Preferably, the concentration of glycyrrhetinic acid in the mixed solution in step 3 is 0.1-0.2 wt%.

[0034] Preferably, in step 4, the concentration ratio of the zinc ion-modified metal-organic framework material to the mixed solution is 5:0.1~1.

[0035] Preferably, the heating and stirring temperature in step 4 is 25~120 ℃, and the heating and stirring time is 2~8 h.

[0036] The present invention also provides the application of the pH-responsive composite hydrogel dressing in the preparation of antibacterial materials.

[0037] Preferably, the bacteria are Gram-positive and Gram-negative bacteria.

[0038] Compared with the prior art, the present invention has the following beneficial effects: (1) The present invention prepares a metal-organic framework material modified with zinc ions and a hydrogel dressing containing glycyrrhetinic acid, which has a dual antibacterial strategy. The hydrogel dressing has antibacterial and anti-biofilm effects on Gram-positive and Gram-negative bacteria. Furthermore, the metal-organic framework material modified with zinc ions has pH responsiveness, marking a paradigm shift from traditional passive bacterial removal to programmed control.

[0039] (2) The hydrogel dressing prepared by the present invention has good mechanical properties and meets the needs of practical use. Attached Figure Description

[0040] Figure 1Infrared spectrum of ZIF-8, a metal-organic framework material modified with zinc ions.

[0041] Figure 2 The image shows the infrared spectrum of ovalbumin and its ovalbumin amyloid fibrils.

[0042] Figure 3 A comparison of the mechanical properties of the composite hydrogel dressings prepared in Examples 1 and 4.

[0043] Figure 4 The pH responsiveness of the composite hydrogel dressing prepared in Example 1.

[0044] Figure 5 The results show the anti-biofilm inhibition of the composite hydrogel dressing prepared in Example 1.

[0045] Figure 6 The results show the anti-biofilm damage effect of the composite hydrogel dressing prepared in Example 1. Detailed Implementation

[0046] To further illustrate the technical means and effects adopted by the present invention in order to achieve the intended purpose, the following detailed description is provided in conjunction with embodiments and comparative examples.

[0047] Unless otherwise specified, the techniques used in the examples are conventional methods well known to those skilled in the art; unless otherwise specified, all reagents used in the examples are commercially available. Ovalbumin was purchased from Shanghai Maclean's Biochemical Technology Co., Ltd., catalog number (CAS: 9006-59-1), for Gram-negative bacteria. E. coli (ATCC25922) and Gram-positive bacteria S. aureus (ATCC33592) was purchased from BioWind International Reagent Import and Export Logistics Center.

[0048] Example 1 A method for preparing a pH-responsive composite hydrogel dressing includes the following steps: Preparation and characterization of zinc ion-modified metal-organic framework material ZIF-8: 0.46 g of zinc acetate and 7.87 g of dimethylimidazole were dissolved in 20 mL and 50 mL of methanol, respectively, to obtain the first precursor and the second precursor. The first precursor and the second precursor were then mixed and refluxed for 24 h. The product was collected by centrifugation (8000 r / min), washed three times with methanol, and dried at 60 °C for 12 h to obtain the zinc ion modified metal-organic framework material, abbreviated as ZIF-8.

[0049] The prepared ZIF-8 solid was characterized by infrared spectroscopy, such as... Figure 1 As shown, the wave number is 422 cm⁻¹.-1 The corresponding Zn-N stretching peak confirms successful coordination between the metal and the ligand; 2924 cm⁻¹ -1 The peak value indicates that the stretching vibration of the ligand CH has been fully incorporated into the skeleton; 1144 cm⁻¹ -1 The CN stretching peaks indicate that the ligands successfully coordinate with metallic Zn via nitrogen atoms.

[0050] Preparation and characterization of ovalbumin amyloid fibrils: 5 g of ovalbumin was completely dissolved in 45 mL of distilled water to prepare a 10 wt% ovalbumin solution. To thoroughly remove excess substances, the ovalbumin solution was dialyzed against distilled water at 4 °C for 3 days. The purified ovalbumin monomers were freeze-dried and then heated at 85 °C for 12 h in a distilled aqueous solution with pH adjusted to 2.0 using hydrochloric acid (HCl) while magnetically stirring to prepare ovalbumin amyloid fibrils.

[0051] The prepared ovalbumin amyloid fibrils were characterized using infrared spectroscopy, such as... Figure 2 As shown, wavenumber 1650 cm -1 The absorption peaks around the left and right are caused by the stretching vibrations of the C=O bonds in the random coil structure of ovalbumin. The absorption peak of natural ovalbumin at this point is 1653 cm⁻¹. -1 The absorption peak of egg white protein after baking was 1630 cm⁻¹. -1 This indicates that the secondary structure of ovalbumin has undergone a change from... α- spiral to β- The significant folding transformation is highly consistent with theoretical predictions of fibrin synthesis. Furthermore, the natural ovalbumin solution exhibits a wavenumber of 1238 cm⁻¹ in the amide III band. -1 There is an absorption peak at a certain point, but after baking under high temperature conditions, the absorption peak shifts to a wavenumber of 1348 cm⁻¹. -1 The location indicates that the secondary structure of ovalbumin has undergone a change from an ordered structure. α- Spiral disorder structure β- Significant transformations of folding or random coiling are observed, likely accompanied by disruption and rearrangement of the hydrogen bond network and dehydration. The subtle vibrations of other labeled chemical bonds further confirm the correctness of ovalbumin amyloid fibril synthesis.

[0052] Preparation of glycyrrhetinic acid solution: 0.002 g, 0.005 g, 0.01 g, 0.02 g, and 0.04 g of glycyrrhetinic acid were completely dissolved in 1 mL of 10 mM Bis-Tris buffer (pH 5.8) to pretreat and obtain glycyrrhetinic acid solutions with concentrations of 0.2–4 wt%.

[0053] Preparation of composite hydrogel dressing: 5 mL of 4 wt% amyloid fibrils solution (obtained by mixing amyloid fibrils with 0.5 M Bis-Tris buffer (pH 6.8) at a volume ratio of 1:1 to 5, and adjusting the pH of the amyloid fibrils solution from 2.0 to 5.8) and 0.2–4 wt% glycyrrhetinic acid solution were magnetically stirred for 30 s at a volume ratio of 1–5:1 to form a mixed solution with a final glycyrrhetinic acid concentration of 0.1–2 wt%. One molar equivalent of ZIF-8 was dispersed in approximately 0.91 mL of a mixed solution containing 0.5 wt% glycyrrhetinic acid. The mixture was heated to 60 °C and stirred for 8 h. After cooling and standing, a composite hydrogel was obtained.

[0054] Example 2 The preparation method of Example 2 is the same as that of Example 1, except that: Two molar equivalents of ZIF-8 were dispersed in approximately 0.91 mL of a mixed solution containing 1 wt% glycyrrhetinic acid. The mixture was heated to 80 °C and stirred for 6 h. After cooling and standing, a composite hydrogel was obtained.

[0055] Example 3 The preparation method of Example 3 is the same as that of Example 1, except that: Three molar equivalents of ZIF-8 were dispersed in approximately 0.91 mL of a mixed solution containing 1.5 wt% glycyrrhetinic acid. The mixture was heated to 100 °C and stirred for 4 h. After cooling and standing, a composite hydrogel was obtained.

[0056] Example 4 The preparation method of Example 4 is the same as that of Example 1, except that: Five molar equivalents of ZIF-8 were dispersed in 10 mL of a mixed solution with a glycyrrhetinic acid concentration of 1 wt%. The mixture was heated to 120 °C and stirred for 2 h. After cooling and standing, a composite hydrogel was obtained.

[0057] Comparative Example 1 The preparation method of Comparative Example 1 is the same as that of Example 1, except that ZIF-8 is not loaded during the preparation of the composite hydrogel dressing. Specifically: Preparation and characterization of ovalbumin amyloid fibrils: 5 g of ovalbumin was completely dissolved in 45 mL of distilled water to prepare a 10 wt% ovalbumin solution. To thoroughly remove excess substances, the ovalbumin solution was dialyzed against distilled water at 4 °C for 3 days. The purified ovalbumin monomers were freeze-dried and then heated at 85 °C for 12 h in a distilled aqueous solution with pH adjusted to 2.0 using hydrochloric acid (HCl) while magnetically stirring to prepare ovalbumin amyloid fibrils.

[0058] Preparation of glycyrrhetinic acid solution: 0.002 g, 0.005 g, 0.01 g, 0.02 g, and 0.04 g of glycyrrhetinic acid were completely dissolved in 1 mL of 10 mM Bis-Tris buffer (pH 5.8) to pretreat and obtain glycyrrhetinic acid solutions with concentrations of 0.2–4 wt%.

[0059] 5 mL of a 4 wt% amyloid fibrillary solution (obtained by mixing amyloid fibrillary with 0.5 M Bis-Tris buffer (pH 6.8) at a volume ratio of 1:1 to 5, and adjusting the pH of the amyloid fibrillary solution from 2.0 to 5.8) and a 1 wt% glycyrrhetinic acid solution were magnetically stirred at a volume ratio of 1:1 for 30 s to form a mixed solution with a final glycyrrhetinic acid concentration of 0.5 wt%.

[0060] Comparative Example 2 The preparation method of Comparative Example 2 is the same as that of Example 1, except that the composite hydrogel dressing is prepared without glycyrrhetinic acid but contains ZIF-8. Specifically: Preparation and characterization of zinc ion-modified metal-organic framework material ZIF-8: 0.46 g of zinc acetate and 7.87 g of dimethylimidazole were dissolved in 20 mL and 50 mL of methanol, respectively, to obtain the first precursor and the second precursor. The first precursor and the second precursor were then mixed and refluxed for 24 h. The product was collected by centrifugation (8000 r / min), washed three times with methanol, and dried at 60 °C for 12 h to obtain the zinc ion modified metal-organic framework material, abbreviated as ZIF-8.

[0061] Preparation and characterization of ovalbumin amyloid fibrils: 5 g of ovalbumin was completely dissolved in 45 mL of distilled water to prepare a 10 wt% ovalbumin solution. To thoroughly remove excess substances, the ovalbumin solution was dialyzed against distilled water at 4 °C for 3 days. The purified ovalbumin monomers were freeze-dried and then heated at 85 °C for 12 h in a distilled aqueous solution with pH adjusted to 2.0 using hydrochloric acid (HCl) while magnetically stirring to prepare ovalbumin amyloid fibrils.

[0062] A composite hydrogel was obtained by dispersing 1 molar equivalent of ZIF-8 in 5 mL of 4 wt% amyloid fibrils solution.

[0063] Comparative Example 3 The preparation method of Comparative Example 3 is the same as that of Example 1, except that: 8 molar equivalents of ZIF-8 are dispersed in about 0.91 mL of a mixed solution with a glycyrrhetinic acid concentration of 0.5 wt%, heated to 60 °C, stirred for 8 h, and then cooled and allowed to stand to obtain a composite hydrogel.

[0064] Detection Example 1 Tensile tests were performed on the composite hydrogel dressings prepared in Examples 1 and 4, such as... Figure 3 As shown, Example 4 has a higher tensile strength at break and better ductility, while Example 1 has greater material strength, stronger resistance to elastic deformation, and is more difficult to stretch.

[0065] Detection Example 2 To demonstrate that the composite hydrogel dressing prepared in Example 1 has pH responsiveness, the composite hydrogel was immersed in phosphate buffered saline (PBS, pH = 5.6–7.0), and the concentration of zinc ions in the leachate was measured every 20 minutes. The results are as follows: Figure 4 As shown (two pH results are presented), when the pH is weakly acidic, the zinc ion release concentration is higher, indicating that the zinc ions are effectively released when the wound healing environment begins to become acidic, which is beneficial to wound healing.

[0066] Detection Example 3 To explore the antibacterial properties of the composite hydrogel dressing, Gram-negative bacteria were tested in the examples and comparative samples. E. coli and Gram-positive bacteria S. aureus The antibacterial activity test was conducted as follows: bacteria were cultured at 37 °C in liquid Luria-Bertani (LB) medium until the exponential growth phase, and then diluted with PBS to 10⁶ CFU / mL. The samples from the examples and comparative examples were added to 800 μL of bacterial suspension and cultured at 37 °C with shaking for 24 h. The number of viable bacteria was detected by the MTT assay. The results are shown in Table 1.

[0067] Table 1. Antibacterial properties of the composite hydrogel dressings in the examples and comparative examples. The results in Table 1 show that the composite hydrogel dressing prepared by mixing ZIF-8 and glycyrrhetinic acid solutions within a suitable concentration range is significantly more effective against the target bacteria than the single material. Furthermore, within a suitable range, the antibacterial performance is enhanced with the increase of ZIF-8 concentration, which strongly demonstrates that the composite hydrogel formed by cross-linking glycyrrhetinic acid with ovalbumin amyloid fibrils and loading ZIF-8 has excellent dual antibacterial properties.

[0068] Detection Example 4 To explore the anti-biofilm properties of composite hydrogel dressings, experiments were conducted on the inhibition and disruption of Gram-positive bacteria biofilms using the composite hydrogel dressings. The specific steps were as follows: Gram-positive Staphylococcus aureus was cultured in liquid LB medium (10... 6 For the biofilm inhibition experiment, Example 1 was added to the bacterial suspension and co-cultured for 24 h. For the mature biofilm disruption experiment, Example 1 was added to the mature biofilm and co-cultured for 24 h and 48 h, respectively. After removing the bacterial liquid with a pipette, the plates were washed with PBS buffer. 100 μL of methanol solution was added to each well for fixation for 15 min, followed by 100 μL of prepared crystal violet staining solution. The plates were stained at room temperature for 30 min, and the PBS buffer washing step was repeated. 100 μL of 33% acetic acid solution was added to each well, and the 96-well plates were sealed with sealing film and incubated at 37 °C on a shaker for 30 min. Finally, the optical density (OD) value at 600 nm was measured using a SpectraMAX ID microplate reader. Results... Figure 5 and Figure 6 As can be seen from the example, Example 1 has a good inhibitory and destructive effect on the biofilm of Gram-positive bacteria.

[0069] The above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention in any way. Although the present invention has been disclosed above with reference to preferred embodiments, it is not intended to limit the present invention. Any person skilled in the art can make some modifications or alterations to the above-disclosed technical content to create equivalent embodiments without departing from the scope of the present invention. Any simple modifications, equivalent changes and alterations made to the above embodiments based on the technical essence of the present invention without departing from the scope of the present invention shall still fall within the scope of the present invention.

Claims

1. A pH-responsive composite hydrogel dressing, characterized in that, A gel formed by cross-linking glycyrrhetinic acid and ovalbumin amyloid fibrils is used as a carrier, and the carrier is loaded with zinc ion modified metal organic framework material.

2. The pH-responsive composite hydrogel dressing according to claim 1, wherein, The zinc ion modified metal organic framework material is at least one of ZIF-8, ZIF-7 and ZIF-90.

3. The pH-responsive composite hydrogel dressing of claim 1, wherein, The mass ratio of glycyrrhetinic acid to ovalbumin amyloid fibrils is 0.1-1:

1. The mass ratio of glycyrrhetinic acid to zinc ion modified metal organic framework material is 0.1-1:

5.

4. The method of claim 1-3, wherein the pH-responsive composite hydrogel dressing is prepared by the steps of: The method comprises the following steps: Step 1: providing zinc ion modified metal organic framework material; Step 2: mixing ovalbumin with deionized water to obtain an ovalbumin solution, and after the ovalbumin solution is hydrated, heating and stirring under acidic conditions to obtain ovalbumin amyloid fibrils; blending the ovalbumin amyloid fibrils with a first buffer solution and adjusting the pH to obtain an ovalbumin amyloid fibril solution; Step 3: dissolving glycyrrhetinic acid in a second buffer solution to obtain a glycyrrhetinic acid solution, and mixing the glycyrrhetinic acid solution with the ovalbumin amyloid fibril solution to obtain a mixed solution; Step 4: dispersing the zinc ion modified metal organic framework material in the mixed solution and heating and stirring to form a pH-responsive composite hydrogel dressing.

5. The production method according to claim 4, characterized by, In step 2, the pH of the blended solution is 2.0-5.

8.

6. The preparation method according to claim 4, characterized in that, The concentration of the ovalbumin amyloid fibril solution in step 2 is 2-6 wt%.

7. The preparation method according to claim 4, characterized in that, The concentration of the glycyrrhetinic acid solution in step 3 is 0.2-0.4 wt%.

8. The preparation method according to claim 4, characterized in that, The concentration of glycyrrhetinic acid in the mixed solution in step 3 is 0.1-0.2 wt%.

9. The preparation method according to claim 4, characterized in that, In step 4, the concentration ratio of the zinc ion modified metal organic framework material to the mixed solution is 5:0.1-1.

10. Use of the pH-responsive composite hydrogel dressing according to any one of claims 1-3 in the preparation of an antibacterial material.

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