An anti-inflammatory and antibacterial hydrogel dressing and its preparation method and application

Abstract

The application discloses an anti-inflammatory and antibacterial hydrogel dressing and a preparation method and application thereof, and relates to the technical field of medical materials, and comprises zinc-iron carbonized nanoparticles and a medical hydrogel, wherein the mass ratio of the zinc-iron carbonized nanoparticles and the medical hydrogel is 1: (50-200), the zinc-iron carbonized nanoparticles are dispersed in the medical hydrogel; the zinc-iron carbonized nanoparticles comprise the following raw materials: zinc gluconate, iron gluconate and L-aspartic acid, and the molar ratio of the zinc gluconate, the iron gluconate and the L-aspartic acid is (0.5-1.5):(0.5-1.5):(1.5-2.0); the medical hydrogel adopts a gelatin-polyethylene glycol hydrogel, which is formed by ultraviolet light curing of gelatin modified by methacrylic anhydride and polyethylene glycol modified by acryloyl chloride. The anti-inflammatory and antibacterial hydrogel dressing disclosed by the application not only has excellent mechanical properties, but also can realize slow release of nanoparticles and exert anti-inflammatory and antibacterial functions.

Description

Technical Field

[0001] This invention relates to an anti-inflammatory and antibacterial hydrogel dressing, its preparation method and application, belonging to the field of drug-loaded hydrogel technology. Background Technology

[0002] Wound healing is a complex physiological process, often hindered by two types of complications: primary complications (such as hemostasis disorders, inflammatory imbalance, abnormal proliferation, and poor tissue remodeling) and secondary complications (including rebleeding, tissue adhesion, exudate accumulation, and excessive scarring). These problems can lead to prolonged hospital stays, permanent tissue damage, and even death. In recent years, various healing-promoting scaffolds have been developed and applied, encompassing hydrogels, sponges, nanofibers, hydrocolloids, and bioprinted structures, among which hydrogels have shown significant potential due to their unique biomimetic properties. However, traditional hydrogels have significant drawbacks: insufficient mechanical properties, potential for biotoxicity, difficulty in controlling drug release, and a lack of anti-inflammatory and antibacterial functions, making it difficult to meet clinical needs. Therefore, developing natural hydrogels with both anti-inflammatory and antibacterial activities has become an important direction for promoting wound healing.

[0003] The introduction of nanoparticles offers a new approach to solving the aforementioned problems: on the one hand, it enhances the mechanical properties of hydrogels; on the other hand, it possesses anti-inflammatory and antibacterial properties, thus being recognized as a feasible strategy for optimizing wound healing. Especially in the field of wound treatment, nanomedicine-based carrier systems (such as biocompatible hydrogel-loaded nanoparticle composite systems) show great promise. These systems can carry commonly used antibacterial nanoparticles such as silver nanoparticles, exerting their efficacy through sustained action; more importantly, they can reduce the development of bacterial resistance, thereby improving the effectiveness and safety of treatment.

[0004] From a pathophysiological perspective, uncontrolled inflammation and bacterial infection are the core factors hindering wound healing; therefore, anti-inflammatory and antibacterial properties are considered key targets for promoting healing. Hydrogels loaded with nanoparticles possessing anti-inflammatory and antibacterial capabilities can precisely address these two issues: the hydrogel itself possesses good biocompatibility, biodegradability, and suitable mechanical properties, providing a suitable microenvironment for the wound; while the nanoparticles can continuously exert anti-inflammatory and antibacterial effects through the sustained-release effect of the hydrogel. In summary, this natural hydrogel composite system with both anti-inflammatory and antibacterial activities holds promise for providing a more efficient and safer innovative treatment option for wound repair. Summary of the Invention

[0005] To address the problems existing in the prior art, the present invention provides an anti-inflammatory and antibacterial hydrogel dressing, its preparation method, and its application.

[0006] To achieve the above objectives, the present invention employs an anti-inflammatory and antibacterial hydrogel dressing, comprising zinc-iron carbon nanoparticles and medical hydrogel, wherein the mass ratio of the zinc-iron carbon nanoparticles to the medical hydrogel is 1:(50-200), and the zinc-iron carbon nanoparticles are dispersed in the medical hydrogel.

[0007] The zinc-iron carbonized nanoparticles comprise the following raw materials: zinc gluconate, ferric gluconate, and L-aspartic acid, wherein the molar ratio of zinc gluconate, ferric gluconate, and L-aspartic acid is (0.5-1.5):(0.5-1.5):(1.5-2.0).

[0008] The medical hydrogel is a gelatin-polyethylene glycol hydrogel, which is formed by curing methacrylic anhydride-modified gelatin and acryloyl chloride-modified polyethylene glycol by ultraviolet light.

[0009] As an improvement, the methacrylic anhydride-modified gelatin is obtained by reacting gelatin with methacrylic anhydride, wherein the mass ratio of gelatin to methacrylic anhydride is 5:(1-4).

[0010] As an improvement, the acryloyl chloride-modified polyethylene glycol is obtained by reacting polyethylene glycol with acryloyl chloride in the presence of an alkaline catalyst, wherein the molar ratio of polyethylene glycol, alkaline catalyst and acryloyl chloride is 1:(2-5):(1.5-2.5).

[0011] A second aspect of the present invention also provides a method for preparing the aforementioned anti-inflammatory and antibacterial hydrogel dressing, comprising the following steps:

[0012] (1) Preparation of zinc-iron carbonized nanoparticles: Zinc gluconate, ferric gluconate and L-aspartic acid were mixed and subjected to hydrothermal reaction to prepare zinc-iron carbonized nanoparticles;

[0013] (2) Preparation of methacrylic anhydride-modified gelatin: gelatin was dissolved in phosphate buffer, methacrylic anhydride was added and reacted, and after neutralization, dialysis and freeze drying, methacrylic anhydride-modified gelatin was obtained.

[0014] (3) Preparation of acryloyl chloride modified polyethylene glycol: polyethylene glycol is dissolved in an organic solvent, and an alkaline catalyst and acryloyl chloride are added under ice bath and nitrogen protection to react. After filtration, dialysis and freeze drying, acryloyl chloride modified polyethylene glycol is obtained.

[0015] (4) Preparation of photocurable hydrogel: The zinc-iron carbonized nanoparticles of step (1), the methacrylic anhydride modified gelatin of step (2), the acryloyl modified polyethylene glycol of step (3) and the photoinitiator are dissolved in phosphate buffer and cured by ultraviolet light.

[0016] As an improvement, in step (1), the temperature of the hydrothermal reaction is 180-200℃ and the reaction time is 4-6 h.

[0017] As an improvement, in step (2), the reaction temperature is 45-55℃; the neutralization is performed by adjusting the pH to 7.4-9.0 using sodium hydroxide solution; and the freeze-drying temperature is -80 to -40℃.

[0018] As an improvement, in step (3), the organic solvent is anhydrous dichloromethane; the ice bath temperature is 0-5℃; the alkaline catalyst is any one of triethylamine, pyridine, N,N-diisopropylethylamine, and 4-dimethylaminopyridine; and the reaction is carried out at room temperature for 6-12 hours.

[0019] As an improvement, in step (4), the photoinitiator is lithium phenyl (2,4,6-trimethylbenzoyl)phosphate; ultraviolet light irradiation for 1-5 minutes.

[0020] A third aspect of the present invention also provides the application of the anti-inflammatory and antibacterial hydrogel dressing described above or the anti-inflammatory and antibacterial hydrogel dressing prepared by the preparation method in the preparation of wound dressing products.

[0021] As an improvement, the wound is a dynamic wound.

[0022] Mechanism of the invention:

[0023] Zinc gluconate, as a dual precursor of zinc and carbon, decomposes into zinc ions and gluconic acid derivatives under high-temperature hydrothermal conditions. The gluconic acid derivatives further carbonize to form carbon nuclei. Similarly, ferric gluconate, also a dual precursor of iron and carbon, decomposes into ferrous ions and gluconic acid derivatives under high-temperature hydrothermal conditions. The latter also further carbonizes to form carbon nuclei. L-Aspartic acid serves as an additional carbon and nitrogen source. Its carboxyl group (-COOH) and amino group (-NH2) participate in dehydration condensation reactions at high temperatures, promoting the formation of carbon dot nuclei.

[0024] The zinc-iron carbide nanoparticles of this invention are prepared from zinc gluconate, ferric gluconate, and L-aspartic acid, and possess multiple effects including antibacterial, anti-inflammatory, and improved mechanical properties. The specific mechanism is as follows: Antibacterial properties: The slow-release Zn in the nanoparticles... 2+ with Fe 2+ Zn can disrupt the integrity of bacterial membranes. 2+ Fe exerts its function by binding to the sulfhydryl groups of membrane proteins. 2+The Fenton reaction generates reactive oxygen species (ROS), ultimately leading to leakage of bacterial contents. Anti-inflammatory properties: The carbon dots formed by ferrous ion doping have the ability to scavenge free radicals, thus achieving an anti-inflammatory effect. Enhanced mechanical properties: On one hand, the functional groups (such as -COOH, -OH) on the surface of zinc-iron carbide nanoparticles can form hydrogen bonds or ionic bonds with the hydrogel network, acting as additional physical cross-linking points to restrict polymer chain movement, thereby increasing the modulus; on the other hand, the nanoparticles uniformly dispersed in the hydrogel effectively hinder the propagation of microcracks through a nano-reinforcement effect similar to a "micro-concrete" structure.

[0025] Compared with the prior art, the beneficial effects of the present invention are:

[0026] (1) With gelatin and polyethylene glycol as the core components, the hydrogel has excellent biocompatibility and adhesion properties; while the introduction of zinc iron carbonized nanoparticles not only significantly enhances the mechanical strength of the hydrogel, but also gives it multiple functions such as scavenging free radicals, anti-inflammatory and antibacterial, which can effectively promote the wound repair process.

[0027] (2) The preparation process of this hydrogel dressing has outstanding advantages such as simple reaction steps, low cost, and green environmental protection. The prepared hydrogel has a stable structure, excellent biocompatibility and strong mechanical properties, and also has the combined functions of scavenging free radicals, anti-inflammatory and antibacterial properties.

[0028] (3) Dispersing zinc-iron carbonized nanoparticles in a gelatin-polyethylene glycol hydrogel system can achieve both slow release of nanoparticles and anti-inflammatory and antibacterial effects, with the dual mechanisms working together to promote effective wound repair.

[0029] (4) Compared with conventional nano-silver, the zinc-iron carbonized nanoparticles of the present invention have better biocompatibility and safety, and zinc ions (Zn) 2+ ) and ferrous ions (Fe 2+ Zn is an essential trace element for the human body, and its cytotoxicity is significantly lower than that of silver ions. 2 + and Fe 2+ While silver ions can be excreted through normal metabolic pathways, they tend to accumulate in the body, and long-term use may lead to organ toxicity. These zinc-iron carbonized nanoparticles endow the hydrogel with additional functional properties; the Zn in the zinc-iron carbonized nanoparticles... 2+ and Fe 2+ It can form coordination bonds with carboxyl and amino groups in hydrogels, giving hydrogels self-repair capabilities and fatigue resistance, while nano-silver does not have this effect and cannot endow hydrogels with similar functions; the zinc-iron carbide nanoparticles have both anti-inflammatory and antibacterial effects. Zinc-iron carbide nanoparticles have the ability to scavenge free radicals and can exert anti-inflammatory effects at the same time, while nano-silver can only achieve antibacterial effects and does not have anti-inflammatory functions. Attached Figure Description

[0030] Figure 1 This is a transmission electron microscope image of zinc-iron carbide nanoparticles in the anti-inflammatory and antibacterial hydrogel dressing prepared in Example 1 of the present invention.

[0031] Figure 2 This is a Zeta potential diagram of zinc-iron carbonized nanoparticles in the anti-inflammatory and antibacterial hydrogel dressing prepared in Example 1 of the present invention.

[0032] Figure 3 This is a hydrated particle size diagram of zinc-iron carbonized nanoparticles in the anti-inflammatory and antibacterial hydrogel dressing prepared in Example 1 of the present invention.

[0033] Figure 4 The figure shows the gelation effect of the anti-inflammatory and antibacterial hydrogel dressing of the present invention; in the figure, (a) is a gelatin-polyethylene glycol hydrogel solution, (b) is a photocurable hydrogel, (c) is a gelatin-polyethylene glycol hydrogel solution loaded with zinc iron carbonized nanoparticles, and (d) is an anti-inflammatory and antibacterial hydrogel dressing.

[0034] Figure 5 Scanning electron microscope images of the comparative hydrogel and anti-inflammatory and antibacterial hydrogel dressing prepared in Example 1 of the present invention;

[0035] Figure 6 Stress-strain diagrams of the comparative hydrogel and the anti-inflammatory and antibacterial hydrogel dressing prepared in Example 1 of the present invention;

[0036] Figure 7 This is a rheological curve of the anti-inflammatory and antibacterial hydrogel dressing of the present invention;

[0037] Figure 8 The UV absorption spectrum of the zinc-iron carbonized nanoparticle solution in the anti-inflammatory and antibacterial hydrogel dressing of the present invention, co-incubated with DPPH.

[0038] Figure 9 The results of cytotoxicity testing of the anti-inflammatory and antibacterial hydrogel dressing of the present invention with L929 cells after co-culturing for 24 h were obtained using the CCK-8 assay.

[0039] Figure 10 The growth curve of Escherichia coli under the treatment of the anti-inflammatory and antibacterial hydrogel dressing of the present invention;

[0040] Figure 11 This is a diagram illustrating the antibacterial effect of the anti-inflammatory and antibacterial hydrogel dressing of the present invention. Detailed Implementation

[0041] To further illustrate the technical means and effects of this invention, the following description, in conjunction with embodiments and accompanying drawings, provides a further explanation of the invention. It is understood that the specific embodiments described herein are merely illustrative of the invention and not intended to limit it.

[0042] Where specific techniques or conditions are not specified in the examples, they shall be performed in accordance with the techniques or conditions described in the literature in this field, or in accordance with the product instructions. Reagents or instruments whose manufacturers are not specified are all conventional products that can be purchased through legitimate channels.

[0043] Example 1

[0044] A method for preparing an anti-inflammatory and antibacterial hydrogel dressing includes the following steps:

[0045] (1) Dissolve zinc gluconate (1 mmol), ferric gluconate (1 mmol) and L-aspartic acid (1.5 mmol) in 20 mL of deionized water and stir for 30 minutes; then transfer the solution to a stainless steel autoclave lined with polytetrafluoroethylene and heat at 180 °C for 4 hours. Centrifuge the suspension and purify the resulting dark brown supernatant by dialysis (MWCO 1000). Then freeze-dry the dialysate in a refrigerator to finally obtain zinc-iron carbide nanoparticles cZnFe@CCs.

[0046] (2) Dissolve 10 g of gelatin powder in 100 mL of PBS buffer preheated to 50°C and stir until completely dissolved (about 30 minutes). Keep the solution at 50°C and add 2 g of MA (methacrylic anhydride) dropwise while stirring at a moderate speed to avoid bubbles. Continue stirring for 3 hours (50°C) in the dark (MA is sensitive to light). Maintain the pH at 7.5 with 5 M NaOH. Put the solution into a dialysis bag and dialyze it in DI water at 40°C for 3 days (changing the water 3 times a day) to remove unreacted MA and small molecule byproducts. After dialysis, pre-freeze the solution at -80°C and then freeze-dry it for 48 hours to obtain porous sponge-like GelMA.

[0047] (3) Dissolve 5 g of PEG (polyethylene glycol) in anhydrous DCM (50 mL), cool to 1°C in an ice bath, purge with nitrogen, slowly add triethylamine (0.7 mL), stir for 10 minutes, dissolve acryloyl chloride (0.2 mL) in 10 mL of dichloromethane, add dropwise through a dropping funnel, keep the temperature at 1°C, and add for about 30 minutes; remove the ice bath, continue the reaction at room temperature (25°C) for 12 hours, filter the reaction solution to remove triethylamine hydrochloride precipitate, remove the solvent by rotary evaporation to obtain a viscous product, dissolve the product in water, dialyze in deionized water for 48 hours using a dialysis bag (MWCO 1k Da), and freeze dry;

[0048] (4) Methacrylic anhydride-modified gelatin, acryloyl chloride-modified polyethylene glycol, lithium phenyl (2,4,6-trimethylbenzoyl)phosphate, and zinc-iron carbonized nanoparticles were dissolved in PBS buffer to obtain a mixture comprising 10% m / v gelatin, 2% m / v polyethylene glycol, 0.25% m / v lithium phenyl (2,4,6-trimethylbenzoyl)phosphate, and 1% m / v zinc-iron carbonized nanoparticles. The mixture was placed in a hydrogel mold and irradiated with ultraviolet light for 3 minutes to obtain the anti-inflammatory and antibacterial hydrogel dressing. This anti-inflammatory and antibacterial hydrogel dressing can be used directly as a routine wound dressing.

[0049] Simultaneously, a contrast hydrogel (hydrogel without zinc-iron carbonized nanoparticles) was prepared. The preparation method of the contrast hydrogel included: dissolving methacrylic anhydride-modified gelatin, acryloyl chloride-modified polyethylene glycol, and phenyl (2,4,6-trimethylbenzoyl) lithium phosphate in PBS buffer to obtain a mixture, placing the mixture in a hydrogel mold, and irradiating it with ultraviolet light to obtain the final product.

[0050] Transmission electron microscopy was performed on the zinc-iron carbide nanoparticles in the anti-inflammatory and antibacterial hydrogel dressing of the present invention, and the results are as follows: Figure 1 As shown in the figure, the zinc-iron carbide nanoparticles are typical monodisperse nanospheres with uniform particle size and pore size, and are uniformly dispersed. The Zeta potential of the zinc-iron carbide nanoparticles in the hydrogel was measured, and the results are as follows: Figure 2 As shown, the Zeta potential is -38.8 V, indicating that the zinc-iron carbide nanoparticles have good stability. The hydrated particle size of the zinc-iron carbide nanoparticles in the hydrogel was measured, and the results are as follows. Figure 3 As shown, the particle size is approximately 10 nm, with a concentrated and uniform particle size distribution, indicating excellent synthesis results. The monodispersity of zinc-iron carbide nanoparticles allows them to be uniformly distributed in the hydrogel, avoiding local aggregation and improving the mechanical properties of the dressing; their small size facilitates in vivo metabolism, reducing the risk of long-term toxicity; and their negative charge properties help to efficiently adsorb and disrupt bacterial membranes, enhancing antibacterial efficacy.

[0051] Figure 4 This image shows the gelation effect of the anti-inflammatory and antibacterial hydrogel dressing. Analysis reveals that the hydrogel exhibits good gelation ability, and its size and shape can be controlled according to actual needs; furthermore, the introduction of zinc-iron carbide nanoparticles did not adversely affect the curing and gelation process of the hydrogel.

[0052] Scanning electron microscopy was used to examine the comparative hydrogel and anti-inflammatory and antibacterial hydrogel dressing prepared in Example 1. The results are as follows: Figure 5As shown in the analysis, the hydrogel still forms a porous structure after the addition of zinc-iron carbonized nanoparticles, with the pore size maintained between 10-30 μm and good pore connectivity. This structure facilitates the efficient exchange of nutrients and metabolic waste on the one hand; on the other hand, the interconnected pores can accelerate the discharge of exudate, avoid the adverse effects caused by the retention of high concentrations of local inflammatory mediators, and further promote the clearance of metabolic waste.

[0053] The stress-strain properties of the prepared comparative hydrogel and anti-inflammatory and antibacterial hydrogel dressings were analyzed, and the results are as follows: Figure 6 As shown, mechanical tests demonstrate that the hydrogel with added zinc-iron carbide nanoparticles exhibits significantly better mechanical properties than the hydrogel without these nanoparticles. This is because: firstly, the functional groups (such as -COOH and -OH) on the surface of the zinc-iron carbide nanoparticles can form hydrogen bonds or ionic bonds with the hydrogel network, acting as additional physical crosslinking points to restrict the movement of polymer chains, thereby increasing the material modulus; secondly, the nanoparticles uniformly dispersed in the hydrogel effectively hinder the propagation of microcracks through a nano-reinforcement effect similar to a "micro-concrete" structure.

[0054] The rheological properties of the prepared hydrogel dressing were analyzed, and the results are as follows: Figure 7 As shown, the storage modulus of this hydrogel is greater than its loss modulus, indicating that it can stably maintain a solid state, even under high-frequency conditions. The high cross-linking density ensures good resistance to deformation and dissolution in clinical use. This property significantly distinguishes it from traditional antibacterial hydrogels (such as brittle gels with simple chemical cross-linking), and it exhibits outstanding application potential, especially in dynamic wound environments (such as joints and burn wounds).

[0055] The ability of zinc-iron carbide nanoparticles in hydrogels to scavenge free radicals was verified: First, a 0.2 mM DPPH ethanol solution was prepared and set aside. Then, 400 μL of solutions containing zinc-iron carbide nanoparticles of different concentration gradients (0-1 mg / mL) were added to 1 mL of DPPH solution, mixed well, and reacted at room temperature in the dark for 30 min. The UV absorption was then measured. The results are as follows: Figure 8 As shown, zinc-iron carbide nanoparticles can effectively scavenge DPPH free radicals, Fe 2+ Donating electrons, it oxidizes itself to Fe. 3+ It directly reduces DPPH. The higher the concentration, the better the removal effect.

[0056] Example 2

[0057] Cytotoxicity of the anti-inflammatory and antibacterial hydrogel dressing prepared in Example 1:

[0058] (1) Culture conditions of L929: Add 3 mL of DMEM culture medium containing 10% fetal bovine serum to a 60 nm cell culture dish and culture it in a constant temperature incubator of 37℃ and 5% CO2. L929 is an adherent cell. When the cells reach 80%, digest them with 1 mL of 0.25% trypsin solution for 2 min. Terminate the trypsin reaction with 1 mL of culture medium containing 10% fetal bovine serum. Repeatedly pipette the cells at the bottom of the dish to disperse them fully. Centrifuge at 100 rpm for 5 min, discard the supernatant, add fresh culture medium to the cell pellet, pipette evenly, and transfer it to a new culture dish at a ratio of 1:4 for continued culture.

[0059] like Figure 9 As shown, the CCK-8 cytotoxicity test results indicate that after L929 cells were co-cultured with GelMA-PEG gel (comparative hydrogel) and cZnFe@CCs GelMA-PEG gel (the anti-inflammatory and antibacterial hydrogel dressing of the present invention) for 24 h, the hydrogel dressing of the present invention maintained the cell survival rate at over 90%, indicating that the anti-inflammatory and antibacterial hydrogel dressing of the present invention has good biocompatibility.

[0060] (2) Take freshly cultured Escherichia coli (E. coli) stock medium (such as LB medium), ensuring that the bacterial culture is in the logarithmic growth phase and at an appropriate concentration. Mix GelMA-PEG gel, cZnFe@CCs GelMA-PEG gel and E. coli bacterial culture in a certain proportion and incubate together. Measure OD at different time points. 600 Numerical values. Take an appropriate amount of the mixture and spread it evenly on the surface of a solid culture medium (such as LB agar plate). Use a spreading stick to rotate and spread the mixture, ensuring that the bacterial solution covers the entire plate. Incubate the plate at 37°C for 24 hours. Observe the colony growth. Figure 10 , Figure 11 As shown, the growth of E. coli co-incubated with cZnFe@CCs GelMA-PEGgel slowed down, indicating that cZnFe@CCs GelMA-PEG gel effectively inhibited the growth of E. coli.

[0061] Example 3

[0062] A method for preparing an anti-inflammatory and antibacterial hydrogel dressing includes the following steps:

[0063] (1) Zinc gluconate (1.5 mmol), ferric gluconate (0.5 mmol) and L-aspartic acid (1.5 mmol) were dissolved in 20 mL of deionized water and stirred for 30 minutes. The solution was then transferred to a stainless steel autoclave lined with polytetrafluoroethylene and heated at 180 °C for 5 hours. The suspension was centrifuged and the resulting dark brown supernatant was purified by dialysis (MWCO 1000). The dialysis solution was then freeze-dried in a refrigerator to finally obtain zinc-iron carbide nanoparticles cZnFe@CCs.

[0064] (2) Dissolve 10 g of gelatin powder in 100 mL of PBS buffer preheated to 55°C and stir until completely dissolved (about 30 minutes). Keep the solution at 50°C and add 4 g of MA dropwise while stirring (at a moderate speed to avoid bubbles). Continue stirring and react for 3 hours (50°C) in the dark (MA is sensitive to light). Maintain pH 8.0 with 5 M NaOH. Put the solution into a dialysis bag and dialyze in DI water at 40°C for 3 days (changing the water 4 times a day) to remove unreacted MA and small molecule byproducts. After dialysis, prefreeze the solution at -80°C and freeze-dry at -60°C for 48 hours to obtain porous sponge-like GelMA.

[0065] (3) Dissolve 5 g PEG in anhydrous DCM (50 mL), cool to 0°C in an ice bath, purge with nitrogen, slowly add triethylamine (0.7 mL), and stir for 10 minutes; dissolve acryloyl chloride (0.4 mL) in 10 mL dichloromethane, add dropwise through a dropping funnel, keep the temperature ≤5°C, add over about 30 minutes, remove the ice bath, and continue the reaction at room temperature (25°C) for 12 hours. Filter the reaction solution to remove triethylamine hydrochloride precipitate; remove the solvent by rotary evaporation to obtain a viscous product, dissolve the product in water, dialyze in deionized water for 48 hours using a dialysis bag (MWCO 1k Da), and freeze dry;

[0066] (4) The methacrylic anhydride-modified gelatin, acryloyl chloride-modified polyethylene glycol, phenyl (2,4,6-trimethylbenzoyl) lithium phosphate and zinc-iron carbonized nanoparticles were dissolved in PBS buffer to obtain a mixture of 10% m / v gelatin, 2% m / v polyethylene glycol, 0.25% m / v phenyl (2,4,6-trimethylbenzoyl) lithium phosphate and 1% m / v zinc-iron carbonized nanoparticles. The mixture was placed in a hydrogel mold and irradiated with ultraviolet light for 5 minutes to obtain the anti-inflammatory and antibacterial hydrogel dressing.

[0067] Example 4

[0068] A method for preparing an anti-inflammatory and antibacterial hydrogel dressing includes the following steps:

[0069] (1) Zinc gluconate (1.2 mmol), ferric gluconate (0.8 mmol) and L-aspartic acid (1.5 mmol) were dissolved in 20 mL of deionized water and stirred for 30 minutes. The solution was then transferred to a stainless steel autoclave lined with polytetrafluoroethylene and heated at 200 °C for 5 hours. The suspension was centrifuged and the resulting dark brown supernatant was purified by dialysis (MWCO 1000). The dialysis solution was then freeze-dried in a refrigerator to finally obtain zinc-iron carbide nanoparticles cZnFe@CCs.

[0070] (2) Dissolve 10 g of gelatin powder in 100 mL of preheated 58°C PBS and stir until completely dissolved (about 30 minutes). Keep the solution at 50°C and add 3 g of MA dropwise while stirring (at a moderate speed to avoid bubbles). Continue stirring and react for 3 hours (50°C) in the dark (MA is sensitive to light). Maintain pH 8.5 with 5 M NaOH. Put the solution into a dialysis bag and dialyze in 40°C DI water for 3 days (changing the water 3 times a day) to remove unreacted MA and small molecule byproducts. After dialysis, prefreeze the solution at -80°C and then freeze-dry it at -40°C for 48 hours to obtain porous sponge-like GelMA.

[0071] (3) Dissolve 5 g PEG in 50 mL anhydrous DCM, cool to 2°C in an ice bath, purge with nitrogen, slowly add 0.7 mL triethylamine, and stir for 10 minutes; dissolve 0.3 mL acryloyl chloride in 10 mL dichloromethane, add dropwise through a dropping funnel, keep the temperature ≤5°C, add over about 30 minutes, remove the ice bath, and continue the reaction at room temperature (25°C) for 12 hours. Filter the reaction solution to remove triethylamine hydrochloride precipitate; remove the solvent by rotary evaporation to obtain a viscous product, dissolve the product in water, dialyze in deionized water for 48 hours using a dialysis bag (MWCO 1kDa), and freeze dry;

[0072] (4) The methacrylic anhydride-modified gelatin, acryloyl chloride-modified polyethylene glycol, phenyl (2,4,6-trimethylbenzoyl) lithium phosphate and zinc-iron carbonized nanoparticles were dissolved in PBS buffer to obtain a mixture of 10% m / v gelatin, 4% m / v polyethylene glycol, 0.25% m / v phenyl (2,4,6-trimethylbenzoyl) lithium phosphate and 1% m / v zinc-iron carbonized nanoparticles. The mixture was placed in a hydrogel mold and irradiated with ultraviolet light for 5 minutes to obtain the anti-inflammatory and antibacterial hydrogel dressing.

[0073] The preparation method of this invention has significant advantages such as simple reaction steps, low cost, and environmental friendliness. The resulting anti-inflammatory and antibacterial hydrogel dressing not only possesses excellent mechanical properties but also enables the slow release of nanoparticles, thereby exerting anti-inflammatory and antibacterial functions.

[0074] This anti-inflammatory and antibacterial hydrogel dressing is suitable for wound dressings in skin wound repair and related treatments. It can also be used as a filler drug system that requires anti-inflammatory and antibacterial properties (such as in skin cancer, dentistry, osteoarthritis, etc.), thus it has broad application prospects.

[0075] 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 or improvements made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. An anti-inflammatory and antibacterial hydrogel dressing, characterized in that, The product comprises zinc-iron carbonized nanoparticles and a medical hydrogel, wherein the mass ratio of the zinc-iron carbonized nanoparticles to the medical hydrogel is 1:(50-200), and the zinc-iron carbonized nanoparticles are dispersed in the medical hydrogel. The zinc-iron carbonized nanoparticles comprise the following raw materials: zinc gluconate, ferric gluconate, and L-aspartic acid, wherein the molar ratio of zinc gluconate, ferric gluconate, and L-aspartic acid is (0.5-1.5):(0.5-1.5):(1.5-2.0). The medical hydrogel is a gelatin-polyethylene glycol hydrogel, which is formed by curing methacrylic anhydride-modified gelatin and acryloyl chloride-modified polyethylene glycol by ultraviolet light.

2. The anti-inflammatory and antibacterial hydrogel dressing according to claim 1, characterized in that, The methacrylic anhydride-modified gelatin is obtained by reacting gelatin with methacrylic anhydride, with a mass ratio of gelatin to methacrylic anhydride of 5:(1-4).

3. The anti-inflammatory and antibacterial hydrogel dressing according to claim 1, characterized in that, The acryloyl chloride-modified polyethylene glycol is obtained by reacting polyethylene glycol with acryloyl chloride in the presence of an alkaline catalyst, wherein the molar ratio of polyethylene glycol, alkaline catalyst and acryloyl chloride is 1:(2-5):(1.5-2.5).

4. A method for preparing an anti-inflammatory and antibacterial hydrogel dressing according to any one of claims 1-3, characterized in that, Includes the following steps: (1) Preparation of zinc-iron carbonized nanoparticles: Zinc gluconate, ferric gluconate and L-aspartic acid were mixed and subjected to hydrothermal reaction to prepare zinc-iron carbonized nanoparticles; (2) Preparation of methacrylic anhydride-modified gelatin: gelatin was dissolved in phosphate buffer, methacrylic anhydride was added and reacted, and after neutralization, dialysis and freeze drying, methacrylic anhydride-modified gelatin was obtained. (3) Preparation of acryloyl chloride modified polyethylene glycol: polyethylene glycol is dissolved in an organic solvent, and an alkaline catalyst and acryloyl chloride are added under ice bath and nitrogen protection to react. After filtration, dialysis and freeze drying, acryloyl chloride modified polyethylene glycol is obtained. (4) Preparation of photocurable hydrogel: The zinc-iron carbonized nanoparticles of step (1), the methacrylic anhydride modified gelatin of step (2), the acryloyl chloride modified polyethylene glycol of step (3) and the photoinitiator are dissolved in phosphate buffer and cured by ultraviolet light irradiation.

5. The method for preparing an anti-inflammatory and antibacterial hydrogel dressing according to claim 4, characterized in that, In step (1), the temperature of the hydrothermal reaction is 180-200℃ and the reaction time is 4-6 h.

6. The method for preparing an anti-inflammatory and antibacterial hydrogel dressing according to claim 4, characterized in that, In step (2), the reaction temperature is 45-55℃; the neutralization is performed by adjusting the pH to 7.4-9.0 with sodium hydroxide solution; and the freeze-drying temperature is -80 to -40℃.

7. The method for preparing an anti-inflammatory and antibacterial hydrogel dressing according to claim 4, characterized in that, In step (3), the organic solvent is anhydrous dichloromethane; the ice bath temperature is 0-5℃; the alkaline catalyst is any one of triethylamine, pyridine, N,N-diisopropylethylamine, and 4-dimethylaminopyridine; and the reaction is carried out at room temperature for 6-12 hours.

8. The method for preparing an anti-inflammatory and antibacterial hydrogel dressing according to claim 4, characterized in that, In step (4), the photoinitiator is lithium phenyl (2,4,6-trimethylbenzoyl)phosphate; ultraviolet light irradiation for 1-5 minutes.

9. The use of an anti-inflammatory and antibacterial hydrogel dressing according to any one of claims 1-3 or an anti-inflammatory and antibacterial hydrogel dressing prepared by the preparation method according to any one of claims 4-8 in the preparation of wound dressing products.

10. The application according to claim 9, characterized in that, The wound is a dynamic wound.

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