Multi-antibacterial composite hydrogel dressing and preparation method thereof

Abstract

The invention relates to a multi-antibacterial composite hydrogel dressing and a preparation method thereof, and the preparation method is characterized by comprising the following steps: (1) dissolving acrylamide and acrylic acid in water according to a mass ratio of 3: 7-7: 3; (2) sequentially adding 0.2 to 35 percent of vanadium trichloride and 0.09 to 15 percent of mangiferin, and uniformly stirring; (3) continuing to add 0.2-2% of N, N '-methylene bisacrylamide and 0.2-2% of ammonium persulfate, stirring and dissolving, adding 0.2-2% of N, N, N', N '-tetramethylethylenediamine, uniformly mixing, and injecting into a mold; (4) standing and reacting at room temperature for 6-48 hours to form tough brown hydrogel; and soaking and washing the brown hydrogel with deionized water for 3-5 times, and then cutting. The multi-antibacterial composite hydrogel dressing has the advantages that the antibacterial rate of the multi-antibacterial composite hydrogel dressing to staphylococcus aureus and escherichia coli is not lower than 70%, and the antibacterial rate can be increased to 80% or above under the assistance of near-infrared light.

Description

Technical Field

[0001] This invention belongs to the field of biomedical materials technology, and relates to a wound dressing, specifically a multi-antibacterial composite hydrogel dressing and its preparation method. Technical Background

[0002] Wound infection is one of the most common and serious challenges in the wound healing process. Traditional dressings, such as gauze, only provide physical isolation and cannot effectively inhibit bacterial growth, and can easily cause secondary damage when changing them. While antibiotic-containing dressings can fight bacteria, long-term use can lead to bacterial resistance. Therefore, the development of non-antibiotic, highly effective, and safe antibacterial dressings is of great significance.

[0003] Hydrogels are considered ideal wound dressing substrates due to their high water content, good biocompatibility, and ability to load active ingredients. In recent years, photothermal therapy (PTT), as a physical antibacterial method, has attracted widespread attention due to its low tendency to induce drug resistance, as it generates localized high temperatures to kill bacteria through photothermal agents under near-infrared light irradiation. However, the photothermal effect alone may lead to excessively high temperatures that burn normal tissue, and the antibacterial efficacy of a single natural antibacterial agent is limited. Summary of the Invention

[0004] The purpose of this invention is to overcome the shortcomings of the prior art and provide a multi-antibacterial composite hydrogel dressing and its preparation method. This multi-antibacterial composite hydrogel dressing possesses both chemical and physical photothermal antibacterial functions, and can enhance its antibacterial function as needed through photothermal effects. It has a broad antibacterial spectrum, is not prone to drug resistance, and can be used for the repair and treatment of chronic wounds, burn wounds, or infected wounds.

[0005] To achieve the above objectives, the technical solution adopted by the present invention is as follows: A multi-antibacterial composite hydrogel dressing is characterized in that: a double-network hydrogel matrix formed by cross-linking polymerization of acrylamide and acrylic acid as monomers contains vanadium trichloride and the natural drug molecule mangiferin, wherein mangiferin is attached to the hydrogel matrix through vanadium ions.

[0006] Furthermore, the vanadium trichloride content in the hydrogel matrix is ​​0.3-30%.

[0007] Furthermore, the mangiferin content in the hydrogel matrix is ​​0.8-60%.

[0008] Furthermore, the aforementioned multi-antibacterial composite hydrogel dressing can raise its surface temperature to 40-55°C within 5-10 minutes under 808 nm near-infrared light irradiation, thus exhibiting photothermal antibacterial capabilities.

[0009] Furthermore, the multi-antibacterial composite hydrogel dressing has an antibacterial rate of no less than 70% against Staphylococcus aureus and Escherichia coli, and the antibacterial rate can be increased to more than 80% under near-infrared light assistance.

[0010] A method for preparing a multi-antibacterial composite hydrogel dressing, characterized by comprising the following steps: (1) Dissolve acrylamide and acrylic acid in water at a mass ratio of 3:7 to 7:3 to obtain a homogeneous mixture A; (2) Add 0.2-35% vanadium trichloride and 0.09-15% mangiferin by weight of mixture A to mixture A in step (1) in sequence, and stir until the mixture is uniform to obtain mixture B; (3) Add 0.2-2% by weight of N,N'-methylenebisacrylamide (crosslinking agent) and 0.2-2% by weight of ammonium persulfate (initiator) to mixture B in sequence. After stirring and dissolving, add 0.2-2% by weight of N,N,N',N'-tetramethylethylenediamine (catalyst) to mixture B. Mix quickly and then pour into the mold. (4) Allow the reaction to stand at room temperature for 6-48 hours to form a tough brown hydrogel; wash the obtained brown hydrogel with deionized water 3-5 times to remove unreacted monomers, and then cut it into the required shape to obtain a multi-antibacterial composite hydrogel dressing.

[0011] Furthermore, in step (2), mangiferin is first dissolved with dimethyl sulfoxide (DMSO).

[0012] This invention uses acrylamide and acrylic acid as monomers and ammonium persulfate as an initiator to form a double-network hydrogel matrix through N,N'-methylenebisacrylamide crosslinking polymerization. It innovatively introduces vanadium trichloride and the natural drug molecule mangiferin as functional composite factors, utilizing their synergistic effect of "chemical antibacterial" and "physical photothermal antibacterial" (the metal coordination of vanadium ions with mangiferin and the carboxyl groups of the hydrogel backbone strengthens the crosslinking structure of the hydrogel, while achieving the sustained release effect of mangiferin and exerting the antibacterial effect of vanadium ions through metal coordination; and increasing the photothermal conversion capacity of the hydrogel through the coordination of vanadium ions), thus realizing an intelligent hydrogel dressing with both chemical antibacterial and controllable physical antibacterial functions.

[0013] When the multi-antibacterial composite hydrogel dressing of this invention is applied to infected wounds, it can inhibit bacterial growth through routine chemical antibacterial action. If the infection worsens or requires intensive treatment, the multi-antibacterial composite hydrogel dressing can be irradiated with near-infrared light for a short period. Under light irradiation, the vanadium / mangiferin complex inside the dressing converts light energy into heat energy, causing a moderate increase in the local temperature of the dressing (e.g., 45-50°C). This gentle thermal effect can effectively disrupt the bacterial cell membrane structure, killing bacteria without causing significant damage to normal tissue. This synergistic effect of "chemical antibacterial" and "physical photothermal antibacterial" achieves a highly efficient, safe, and intelligent antibacterial effect.

[0014] Compared with the prior art, the present invention has the following advantages: 1. It combines the natural chemical antibacterial properties of mangiferin, the chemical antibacterial properties of vanadium ions, and the physical photothermal antibacterial properties. The triple mechanism works synergistically, resulting in strong antibacterial efficacy and low likelihood of drug resistance. 2. The photothermal antibacterial function can be precisely controlled by external near-infrared light to achieve "on-demand treatment" and avoid potential tissue damage caused by long-term use of antibiotics or continuous high temperature. 3. Made from natural antibacterial agent mangiferin and biocompatible polymers, it has high safety, and the moist environment of the hydrogel is conducive to wound healing. 4. The one-step free radical polymerization method is simple and easy to scale up for production. Attached Figure Description

[0015] Figure 1 This is a schematic diagram illustrating the preparation of a multi-antibacterial composite hydrogel dressing. Figure 2 This is a curve showing the temperature change of a multi-antibacterial composite hydrogel dressing under different sunlight intensities as a function of irradiation time. Figure 3 This image shows the antibacterial effect of a multi-antibacterial composite hydrogel dressing under light and without light. Detailed Implementation

[0016] A method for preparing a multi-antibacterial composite hydrogel dressing, the specific implementation steps of which are as follows: Example 1

[0017] (1) Dissolve 1.2 g of acrylamide and 1.12 mL of acrylic acid in 10 mL of water; (2) Add 20 mg of vanadium trichloride and 9 mg (mangiferin was dissolved in 100 μL DMSO beforehand) to the above solution and continue stirring until the mixture is homogeneous; (3) Add 40 mg sequentially N , N'-Methylenebisacrylamide (crosslinking agent) and 150 mg ammonium persulfate (initiator) were stirred and dissolved, and finally 40 μL was added. N , N , N ', N '-Tetramethylethylenediamine (catalyst), after rapid mixing, is injected into molds (cylindrical and disc-shaped); (4) Allow the reaction to stand at room temperature for 24 hours to form a tough brown hydrogel; wash the obtained brown hydrogel twice with deionized water to remove unreacted monomers, and then cut it into the required shape to obtain a multi-antibacterial composite hydrogel dressing. Example 2

[0018] (1) Dissolve 1.2 g of acrylamide and 0.5 mL of acrylic acid in 10 mL of water; (2) Add 300 mg of vanadium trichloride and 9 mg (mangiferin was dissolved in 100 μL DMSO beforehand) to the above solution and continue stirring until the mixture is homogeneous; (3) Add 40 mg sequentially N , N '-Methylenebisacrylamide (crosslinking agent) and 150 mg ammonium persulfate (initiator) were stirred and dissolved, and finally 40 μL was added. N , N , N ', N '-Tetramethylethylenediamine (catalyst), after rapid mixing, is injected into molds (cylindrical and disc-shaped); (4) The reaction was allowed to stand at room temperature for 26 hours to form a tough brown hydrogel. The brown hydrogel was washed three times with deionized water to remove unreacted monomers, and then cut into the required shape to obtain a multi-antibacterial composite hydrogel dressing. Example 3

[0019] (1) 1.2 g of acrylamide and 2.7 mL of acrylic acid were dissolved in 10 mL of water; (2) Add 300 mg of vanadium trichloride and 18 mg (mangiferin was dissolved in 200 μL DMSO beforehand) to the above solution and continue stirring until the mixture is homogeneous; (3) Add 40 mg sequentially N , N '-Methylenebisacrylamide (crosslinking agent) and 150 mg ammonium persulfate (initiator) were stirred and dissolved. Finally, 40 μL of N,N,N',N'-tetramethylethylenediamine (catalyst) was added, and the mixture was quickly mixed and poured into molds (cylindrical and disc). (4) Allow the reaction to stand at room temperature for 22 hours to form a tough brown hydrogel; wash the obtained brown hydrogel with deionized water 5 times to remove unreacted monomers, and then cut it into the required shape to obtain a multi-antibacterial composite hydrogel dressing.

[0020] Finally, it should be noted that the above embodiments are only for illustration and not for limiting the technical solutions of the present invention. Any equivalent substitutions, modifications or partial substitutions that do not depart from the spirit and scope of the present invention should be covered within the protection scope of the claims of the present invention.

Claims

1. A method for preparing a multi-antibacterial composite hydrogel dressing, characterized in that... Includes the following steps: (1) Dissolve acrylamide and acrylic acid in water at a mass ratio of 3:7 to 7:3 to obtain a homogeneous mixture A; (2) Add 0.2-35% vanadium trichloride and 0.09-15% mangiferin by weight of mixture A to mixture A in step (1) in sequence, and stir until the mixture is uniform to obtain mixture B; (3) Add 0.2-2% N,N'-methylenebisacrylamide and 0.2-2% ammonium persulfate by weight of mixture B to mixture B in sequence. After stirring and dissolving, add 0.2-2% N,N,N',N'-tetramethylethylenediamine by weight of mixture B. Mix well and pour into the mold. (4) Allow the reaction to stand at room temperature for 6-48 hours to form a tough brown hydrogel; soak and wash the obtained brown hydrogel with deionized water 3-5 times, and then cut it into the required shape to obtain a multi-antibacterial composite hydrogel dressing.

2. The method for preparing a multi-antibacterial composite hydrogel dressing according to claim 1, characterized in that: In step (2), mangiferin is first dissolved with dimethyl sulfoxide.

3. A multi-antibacterial composite hydrogel dressing prepared according to the method of claim 1 or 2, characterized in that: The double-network hydrogel matrix formed by cross-linking polymerization of acrylamide and acrylic acid contains vanadium trichloride and the natural drug molecule mangiferin, in which mangiferin is attached to the hydrogel matrix through vanadium ions.

4. The multi-antibacterial composite hydrogel dressing according to claim 3, characterized in that: The vanadium trichloride content in the hydrogel matrix is ​​0.3-30%.

5. The multi-antibacterial composite hydrogel dressing according to claim 3, characterized in that: The mangiferin content in the hydrogel matrix is ​​0.8-60%.

6. The multi-antibacterial composite hydrogel dressing according to claim 3, characterized in that: A multi-antibacterial composite hydrogel dressing can raise its surface temperature to 40-55°C within 5-10 minutes under 808 nm near-infrared light irradiation, thus exhibiting photothermal antibacterial capabilities.

7. The multi-antibacterial composite hydrogel dressing according to claim 3, characterized in that: A multi-antibacterial composite hydrogel dressing has an antibacterial rate of no less than 70% against Staphylococcus aureus and Escherichia coli, and the antibacterial rate can be increased to more than 80% under the assistance of near-infrared light.

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