A chitosan-based hydrogel, a preparation method and application in bacterial infection wound healing

Abstract

The application provides a chitosan-based hydrogel and a preparation method and application thereof, and belongs to the field of chemical synthesis and biomedical technology. The chitosan-based hydrogel is obtained by cross-linking a carboxymethyl chitosan main structure and a cross-linking agent synthesized according to formula 1. The application also provides application of the chitosan-based hydrogel in preparation of a wound healing drug for treating bacterial infection. The chitosan-based hydrogel has excellent bioluminescence performance and can detect the strength of inflammation at a wound site. The prepared hydrogel material has the effects of photothermal, photodynamic, near-infrared light catalytic cage release of H2S, antibacterial and wound healing.

Description

Technical Field

[0001] This invention belongs to the fields of chemical synthesis and biomedical technology, specifically relating to a chitosan-based hydrogel, its preparation method, and its application in healing bacterial infection wounds. Background Technology

[0002] Skin wound healing is a highly complex biological process involving the precise collaboration of multiple cells and signaling pathways. When the skin barrier is damaged, tissues are exposed to the external environment, making them highly susceptible to bacterial infection. Infection is a key factor hindering and delaying normal wound healing. Currently, the widespread use of antibiotics has led to drug resistance in some pathogens. Therefore, the development of multifunctional biomaterials that are antibiotic-independent and possess both highly effective antibacterial and active wound-healing functions has become an urgent need.

[0003] Hydrogels, as soft materials with a three-dimensional network structure, are ideal candidates for multifunctional wound dressings. They provide a moist microenvironment for the wound, allowing oxygen and water molecules to permeate, absorbing excess exudate, and physically blocking microorganisms. These properties are crucial for promoting fibroblast proliferation, keratinocyte migration, and eventual re-epithelialization during the wound healing process.

[0004] Under light irradiation, bacteria are inhibited or killed by the activation of photosensitizers, either by reacting with cellular substrates or by forming reactive oxygen species (ROS) through energy transfer reactions. However, photodynamic therapy (PDT) alone has a relatively weak antibacterial effect. Therefore, it is necessary to combine PDT with other antibacterial therapies to achieve multimodal combined treatment. Photothermal therapy (PTT) is a treatment method that exposes a photosensitizer to a light source of a specific wavelength, generating sufficient heat to cause cell membrane rupture and protein denaturation, thereby leading to bacterial death. Furthermore, phototherapy has many advantages: it is targeted, penetrates deep tissues / biomembranes, is remotely controlled, non-invasive, has rapid effects, and has fewer side effects.

[0005] Bioorthogonal chemistry, especially bioorthogonal degradation reactions triggered by external stimuli, has shown great potential in remotely controlled applications. However, traditional ultraviolet light-triggered systems suffer from limitations such as high cytotoxicity and poor tissue penetration. Recent research has focused on redshifting the excitation wavelength to the visible light region, but this is still constrained by strong scattering from biological tissues. In contrast, near-infrared light with wavelengths in the 700-1000 nm range lies within the "therapeutic optical window," offering superior tissue penetration depth, lower phototoxicity, and less biological background interference, making it a highly promising remote triggering light source.

[0006] Iridium complexes have been widely used as photosensitizers in photodynamic therapy due to their significant spin-orbit coupling effect, high luminescence quantum efficiency, long excited-state lifetime, excellent photostability, and ease of structural modification. However, there are few reports on designing iridium complex systems that can operate efficiently in the near-infrared region and integrate photocatalytic reaction mechanisms to synergistically promote the healing of bacterial-infected wounds. Developing such near-infrared responsive iridium complex systems is expected to provide new ideas for constructing novel intelligent antibacterial and healing-promoting materials, and has significant research value and application potential. Summary of the Invention

[0007] This invention provides a chitosan-based hydrogel, its preparation method, and its applications. The chitosan-based hydrogel of this invention first prepares a porphyrin-iridium complex conjugate, enabling it to crosslink and form a hydrogel via a Schiff base reaction. Simultaneously, it possesses excellent photothermal and photodynamic therapy capabilities, chemiluminescence diagnostic capabilities, and photocatalytic drug release effects, thereby achieving antibacterial and wound-healing promotion effects.

[0008] This invention first provides a chitosan-based hydrogel, which is obtained by crosslinking carboxymethyl chitosan with a crosslinking agent synthesized as shown in Formula 1. Formula 1.

[0009] This invention also provides a method for preparing chitosan-based hydrogels, comprising the following steps: Step 1: Pyridine-2-carboxaldehyde and 4-(10,15,20-triphenylporphyrin-5-yl)aniline are heated under reflux in the presence of ethanol to obtain porphyrin Schiff base ligands; Step 2: Under nitrogen protection, IrCl3·3H2O and 4-(2-pyridyl)-benzaldehyde ligand are heated under reflux to obtain 4-(2-pyridyl)-benzaldehyde iridium dichlorobridge; Step 3: Under nitrogen protection, the 4-(2-pyridyl)-benzaldehyde iridium dichlorobridge from Step 2 and the porphyrin Schiff base ligand from Step 1 were placed in the dark and refluxed in the presence of a solvent. After the reaction was completed, potassium hexafluorophosphate was added and stirring was continued to obtain the metal iridium complex TJOIR shown in Formula 1. Step 4: Dissolve carboxymethyl chitosan (CMCS) and the metal iridium complex TJOIR shown in Formula 1 in a solvent, mix them, stir, and let stand at room temperature to obtain the chitosan-based hydrogel.

[0010] Preferably, the molar ratio of pyridine-2-carboxaldehyde to 4-(10,15,20-triphenylporphyrin-5-yl)aniline in step one is 2:1.

[0011] Preferably, the reaction temperature in step one is 78-90 ℃ and the reaction time is 8-12 h.

[0012] Preferably, the reaction temperature in step two is 120℃-130℃, and the reaction time is 24-30 h.

[0013] Preferably, the molar ratio of IrCl3·3H2O and 4-(2-pyridyl)-benzaldehyde in step two is 1:(2.5-3).

[0014] Preferably, the reflux reaction in step three is carried out at a temperature of 75 ℃-90 ℃ and for a reaction time of 8-12 h.

[0015] Preferably, the molar ratio of the 4-(2-pyridyl)-benzaldehyde iridium dichlorobridge and the porphyrin Schiff base ligand in step three is 1:2.

[0016] Preferably, the mass ratio of CMCS to TJOIR in step four is 10:1.

[0017] The present invention also provides the application of the above-mentioned chitosan-based hydrogel in the preparation of a drug for treating bacterial infection wound healing.

[0018] Beneficial effects of the present invention This invention provides a chitosan-based hydrogel, its preparation method, and its applications. The invention synthesizes a dynamically responsive hydrogel through Schiff base crosslinking of carboxymethyl chitosan with a TJOIR crosslinking agent. Firstly, carboxymethyl chitosan itself is an antibacterial material, achieving certain antibacterial, anti-inflammatory, and antioxidant effects. This platform, through the coordination of Ir(III) complexes, significantly enhances the molar extinction coefficient and intersystem crossing efficiency of the photosensitizer, thereby synergistically strengthening photothermal conversion efficiency and ROS generation capacity, achieving efficient removal of deep biofilms. More importantly, this invention cleverly utilizes the photocatalytic properties of this Ir-based photosensitizer, integrating it with a bio-orthogonal precursor drug to innovatively achieve near-infrared light-triggered, spatiotemporally controllable H2S gas release. This process can precisely respond to the lesion microenvironment, thereby simultaneously exerting multiple healing regulatory functions such as anti-inflammatory, antioxidant, and angiogenesis-promoting effects. Simultaneously, the ONOO in the platform... - Responsive chemiluminescent probes can be specifically activated at sites of infection and inflammation, generating near-infrared luminescence signals with a high signal-to-noise ratio, enabling in-situ, dynamic, and non-invasive visual monitoring of wound conditions. This invention not only provides a novel diagnostic and treatment strategy for overcoming drug-resistant deep tissue infections with strong penetration, synergistic function, and on-demand regulation, but also offers innovative ideas for the design paradigm of next-generation "therapeutic" biomaterials through the cross-integration of metal coordination chemistry, bioorthogonal catalysis, and smart materials science. Attached Figure Description

[0019] Figure 1 This is a schematic diagram illustrating the preparation of TJOIR as described in Example 1 of the present invention; Figure 2 The TJOIR 1H NMR spectrum prepared in Example 1 of this invention; Figure 3 The UV absorption spectrum and fluorescence emission spectrum of TJOIR prepared in aqueous solution in Example 1 of this invention are shown below. Figure 4 Photothermal data of the CMTJOIR hydrogel prepared in Example 2 of this invention; Figure 5 This is a thermal imaging data image of the CMTJOIR hydrogel prepared in Example 2 of the present invention; Figure 6 The diagram shows the ROS generation of the CMTJOIR hydrogel prepared in Example 2 of this invention. Figure 7 The rheological properties of the CMTJOIR hydrogel prepared in Example 2 of this invention are shown in the diagram. Figure 8 This is a graph showing the acoustic catalysis experimental data of the CMTJIOR hydrogel prepared in Example 2 of this invention; Figure 9 The chemiluminescence properties of CMTJOIR prepared in Example 2 of this invention are shown in the figure. Figure 10 The image shows a hemolysis test result of the CMTJOIR hydrogel prepared in Example 2 of this invention. Figure 11 The image shows the antibacterial test results of the CMTJOIR hydrogel prepared in Example 2 of this invention against different bacterial species. Figure 12 The graph shows the cell viability and antioxidant properties of the CMTJOIR hydrogel prepared in Example 2 of this invention after being cultured in HUVEC cells for 24 h. Figure 13 Chemiluminescence imaging of the CMTJOIR hydrogel prepared in Example 2 of this invention at the site of a rat wound; Figure 14 The image shows the healing effect of the CMTJOIR hydrogel prepared in Example 2 of this invention on the surface of a rat wound. Detailed Implementation

[0020] This invention first provides a chitosan-based hydrogel, which is obtained by crosslinking carboxymethyl chitosan with a crosslinking agent synthesized as shown in Formula 1. Formula 1.

[0021] The carboxymethyl chitosan mentioned above is commercially available and has the following structural formula:

[0022] This invention also provides a method for preparing chitosan-based hydrogels, the preparation process of TJOIR as follows: Figure 1 As shown, it includes the following steps: Step 1: Pyridine-2-carboxaldehyde and 4-(10,15,20-triphenylporphyrin-5-yl)aniline are heated under reflux in the presence of ethanol to obtain porphyrin Schiff base ligands; Step 2: Under nitrogen protection, IrCl3·3H2O and 4-(2-pyridyl)-benzaldehyde ligand are heated under reflux to obtain 4-(2-pyridyl)-benzaldehyde iridium dichlorobridge; Step 3: Under nitrogen protection, the 4-(2-pyridyl)-benzaldehyde iridium dichlorobridge from Step 2 and the porphyrin Schiff base ligand from Step 1 were placed in the dark and refluxed in the presence of a solvent. After the reaction was completed, potassium hexafluorophosphate was added and stirring was continued to obtain the metal iridium complex TJOIR shown in Formula 1. Step 4: Dissolve carboxymethyl chitosan (CMCS) and the metal iridium complex TJOIR shown in Formula 1 in a solvent, mix them, stir, and let stand at room temperature to obtain the chitosan-based hydrogel.

[0023] According to the present invention, pyridine-2-carboxaldehyde and 4-(10,15,20-triphenylporphyrin-5-yl)aniline are added to a reaction vessel and heated under reflux in ethanol. The preferred reaction temperature is 78-90 °C and the preferred reaction time is 8-12 h. After the reaction is cooled to room temperature, a large amount of ethanol is added to precipitate the solid, which is then filtered. The resulting solid is dried to obtain the porphyrin Schiff base ligand. The preferred molar ratio of pyridine-2-carboxaldehyde to 4-(10,15,20-triphenylporphyrin-5-yl)aniline is 2:1.

[0024] According to the present invention, IrCl3·3H2O and 4-(2-pyridyl)-benzaldehyde ligand are added to a reaction vessel containing solvent and water. The reaction is carried out under a nitrogen-protected atmosphere and heated to reflux. The preferred reaction temperature is 120℃-130℃, and the preferred reaction time is 24-30 h. After the reaction is cooled to room temperature, a large amount of water, a poor solvent, is added to precipitate the solid, which is then filtered. The precipitate is washed multiple times with a large amount of water and solvents such as ethanol. The resulting solid, when dried, is the 4-(2-pyridyl)-benzaldehyde iridium dichlorobridge. The preferred solvent is 2-ethylene glycol ethyl ether, and the preferred molar ratio of IrCl3·3H2O to the 4-(2-pyridyl)-benzaldehyde ligand is 1:(2.5-3).

[0025] According to the present invention, the 4-(2-pyridyl)-benzaldehyde iridium dichlorobridge and porphyrin Schiff base ligand obtained above are added to a reaction vessel, followed by the addition of a solvent, preferably dichloromethane and methanol (v:v = 1:1). Under the condition of sufficient purging with inert gas N2, the reaction is carried out in the dark under reflux. The preferred reaction temperature is 75 ℃-90 ℃, and the preferred reaction time is 8-12 h. After the reaction is completed and cooled to room temperature, potassium hexafluorophosphate solid is added to the solution in the flask, and stirring is continued at room temperature. The preferred stirring time is 45-60 min. The solvent in the system is removed using a rotary evaporator, followed by extraction with dichloromethane and water to remove excess potassium hexafluorophosphate solid. The obtained substance is washed with petroleum ether and dried, then purified by column chromatography to obtain a purple-red solid, which is TJOIR. The preferred molar ratio of the 4-(2-pyridyl)-benzaldehyde iridium dichlorobridge and porphyrin Schiff base ligand is 1:2. The preferred molar ratio of TJOIR complex to potassium hexafluorophosphate is 10:1.

[0026] According to this invention, CMCS is dissolved in PBS, and the crosslinking agent TJOIR is dissolved in dimethyl sulfoxide. The mixture is stirred and allowed to stand for 20-60 minutes. Then, the hydrogel is placed in PBS to exchange the solvent and displace the DMSO. The mass ratio of CMCS to TJOIR is 10:1; the ratio of water to dimethyl sulfoxide is v:v = 20:1.

[0027] The present invention also provides the application of the above-mentioned chitosan-based hydrogel in the preparation of a drug for treating bacterial infection wound healing.

[0028] The present invention is further described below through the following embodiments, which are not intended to limit the present invention in any way. Any modifications or alterations made to the present invention that are easily implemented by those skilled in the art without departing from the technical solutions of the present invention shall fall within the scope of the claims of the present invention.

[0029] Example 1: Preparation of TJOIR Step 1: Add pyridine-2-carboxaldehyde (0.2 mmol, 0.0214 g) and 4-(10,15,20-triphenylporphyrin-5-yl)aniline (0.1 mmol, 0.0630 g) to a 100 mL single-necked flask, using 60 mL of ethanol as the solvent. Reflux the reaction for 12 h. After the reaction is complete and cooled to room temperature, add a large amount of ethanol to the solution in the flask to precipitate the precipitate. Filter the precipitate and wash it repeatedly with a large amount of ethanol. The resulting solid, once dried, is the porphyrin Schiff base ligand.

[0030] Step 2: Add IrCl3·3H2O (0.1 mmol, 0.0352 g) and 4-(2-pyridyl)-benzaldehyde (0.3 mmol, 0.054 g) to a round-bottom flask containing 30 mL of 2-ethylene glycol ethyl ether and 10 mL of water. Heat under reflux for 24 h under N2 protection. After the reaction cools to room temperature, add a large amount of water (a poor solvent) to precipitate the precipitate. Filter the precipitate and wash it multiple times with a large amount of water and solvents such as ethanol. The resulting solid, when dried, is 4-(2-pyridyl)-benzaldehyde iridium dichlorobridge.

[0031] Step 3: Add 4-(2-pyridyl)-benzaldehyde iridium dichlorobridge (0.1 mmol, 0.118 g) and porphyrin Schiff base ligand (0.2 mmol, 0.129 g) to a 100 mL single-necked flask, using 60 mL of dichloromethane and methanol (v:v = 1:1) as the solvent. Under a full purging of inert gas N2, reflux the reaction in the dark for 8 h. After the reaction is complete and cooled to room temperature, add 10 times the equivalent of the iridium complex in potassium hexafluorophosphate solid to the solution in the flask, continue stirring at room temperature for 45 min, remove the solvent using a rotary evaporator, extract with dichloromethane and water to remove excess potassium hexafluorophosphate solid, wash the obtained substance with petroleum ether and dry, purify by column chromatography, and obtain a purple-red solid, which is TJOIR. The NMR spectrum is shown below. Figure 2 As shown, this invention successfully synthesized the structure.

[0032] Example 2: Preparation of CMTJOIR hydrogel CMCS was dissolved in PBS (0.1 g, 1 mL), and TJOIR prepared in Example 1 was dissolved in dimethyl sulfoxide (0.01 g, 0.05 mL). After mixing, the mixture was left to stand at room temperature for 20 min to obtain CMTJOIR hydrogel. The wet hydrogel was then immersed in deionized water to remove excess solvent DMSO.

[0033] Comparative Example 1 The preparation process and conditions were the same as in Example 2, except that TJOIR was replaced with TJOH (commercially available, Chinese name: 4,4-(10,20-diphenylporphyrin-5,15-diyl)diphenylformaldehyde) to obtain CMTJOH hydrogel.

[0034] The chitosan-based hydrogels prepared in Comparative Example 1 and Example 2 were characterized in the following ways: 1. Photophysical properties of TJOIR In this invention, the photophysical properties of TJOIR were determined in aqueous solution. Figure 3The ultraviolet absorption spectrum of TJOIR in aqueous solution according to the present invention ( Figure 3 A) and fluorescence emission spectrum ( Figure 3 B), As can be seen from the figure, TJOIR exhibits bright red light emission in aqueous solution, with an emission peak at 648 nm.

[0035] 2. Photothermal properties of chitosan-based hydrogels Figure 4 The image shows the photothermal data of the CMTJOIR hydrogel prepared in Example 2 of this invention. Figure 4 A is the control group. Figure 4 B. Temperature changes under different power levels Figure 4 C represents the photothermal cycle of the drug. Figure 4 Figure A shows that the drug group has a better photothermal generation capacity compared to the control group H2O; Figure 4 Figure B shows that the CMTJIOR hydrogel exhibits a power-dependent characteristic: the higher the power, the higher the heat generation and temperature rise. Figure 4 The image in Figure C shows the temperature change of the CMTJIOR hydrogel after five heating and cooling cycles, demonstrating that the drug has good photothermal cycling ability.

[0036] Figure 5 This is a thermal image of the CMTJIOR hydrogel corresponding to photothermal data. Under illumination, the solution temperature increases with the extension of illumination time.

[0037] 3. Singlet oxygen generation capacity of chitosan-based hydrogels Figure 6 CMTJOH (prepared according to the present invention) Figure 6 A), CMTJOIR ( Figure 6 B), in vitro singlet oxygen production experiments under illumination and DPBF conditions and related kinetic curves ( Figure 6 C, 6D), from Figure 6 It can be seen that CMTJOIR has excellent singlet oxygen generation ability.

[0038] 4. Rheological property testing of chitosan-based hydrogels: Figure 7 The rheological properties of the CMTJIOR hydrogel of this invention were tested. Figure 7 A is the rheological stress diagram. Figure 7 B is the frequency spectrum. Figure 7 C represents the shear injectability performance diagram. Figure 7 D represents the cyclic steady-state performance diagram. Figure 7 A and Figure 7 B indicates that the material has good mechanical properties. Figure 7 C and 7D show that the material has self-healing and injectable properties.

[0039] 5. Photocatalytic experiments of chitosan-based hydrogels Figure 8 The photocatalytic experimental data of CMTJIOR hydrogel were used to measure the photocatalytic reduction capacity of the drug in different control groups. Figure 8 A demonstrates that, compared to CMTJOH, the CMTJOIR hydrogel exhibits a stronger gas generation capability. Figure 8 B indicates that the release of hydrogen sulfide gas from the drug can only be catalyzed more quickly when O2, NIR, NADH, and the catalyst are present together.

[0040] 6. Chemiluminescence experiment of chitosan-based hydrogel Figure 9 The relevant chemiluminescence data for CMTJOIR are presented in the table below. Related chemiluminescence tests were performed using an IVIS mouse in vivo imaging system. See also... Figure 9 In Figure A, under different luminescence responses of hydrogels to ONOO-, the CMTJOIR hydrogel exhibits the strongest luminescence level. (See also...) Figure 9 In section B, different types of ROS were co-incubated with CMTJOIR in a 96-well plate under different ROS responses. - The strongest luminescence intensity was observed at the site of inflammation in rat wounds. - As a marker substance, it can respond to CMTJOIR hydrogel to produce chemiluminescence, illuminating inflamed areas. See also Figure 9 In C, different proportions of ONOO - The results of coexistence measurements with the drug showed a linear correlation. Figure 9 The dotted-line plot of chemiluminescence intensity at different wavelengths shows that the drug exhibits the highest intensity of bioluminescence emission at 660 nm. See also Figure 9 In the E-type drug, chicken breast of varying thicknesses is coated onto the drug, allowing its chemiluminescence to penetrate up to 12 mm. This high penetration depth is beneficial for imaging and testing the drug at deep inflammatory sites. This method offers significant advantages over photosensitizers that rely on short-wavelength excitation light.

[0041] 7. Hemolysis test of chitosan-based hydrogels: Figure 10 For the hemolysis test of the CMTJOIR hydrogel of this invention, different concentrations of CMTJOIR hydrogel were co-incubated with red blood cells in a 37 ℃ oven for 2 h. The PBS group was used as the negative control group, and the water group was used as the positive control group. In the figure, inset a) shows the visual diagram obtained by centrifugation after co-incubating the corresponding concentration of CMTJOIR hydrogel with red blood cells in hot water at 37 ℃ for 2 h. Inset b) shows the visual diagram of the corresponding concentration of CMTJOIR hydrogel. The hemolysis rate of the drug was still less than 5% at 6 mg / mL, which shows good biocompatibility.

[0042] 8. Antibacterial test of chitosan-based hydrogel: Figure 11 To assess the antibacterial properties of the CMTJOIR hydrogel of this invention, the ability of the drug group to inhibit the growth of aerobic Staphylococcus aureus was measured compared to the control group. Figure 11 A, B), and a better ability to inhibit the growth of E. coli ( Figure 11 C,D).

[0043] 9. Cell therapy experiments using chitosan-based hydrogels: Figure 12 Figure A shows the cell viability of the CMTJOIR hydrogel of this invention after 24 h of culture in human umbilical vein endothelial cells (HUVECs). The 3-(4,5-dimethylthiazol-2)-2,5-diphenyltetrazolium bromide (MTT) assay of the CMTJOIR hydrogel of this invention was used to study the potential toxicity of the CMTJOIR hydrogel to HUVEC cells. The MTT assay for drug cytotoxicity was performed as follows: HUVEC cells were seeded at a density of 10,000 cells per well in a 96-well plate. Cells were cultured at 37 °C and 5% CO2 for 24 hours. After removing the old culture medium, drug intervention was performed by adding 100 μL of DMEM medium containing different concentration gradients of the drug (0-6 mg / mL) to each well. After 4 hours, the original culture medium was replaced with 100 μL of fresh DMEM medium. Cells were incubated for 24 hours. 20 μL of MTT at a concentration of 5 mg / mL was added to each well. Cells were incubated for 4 hours. After 4 hours, 150 μL of DMSO was added to each well to replace the original culture medium. The absorbance of the samples at 570 nm was measured using a microplate reader. Figure 12 As shown in Figure A, even when the concentration of the drug CMTJOIR reaches a relatively high level of 6 mg / mL, the survival rate of cells incubated with CMTJOIR hydrogel remains above 96%, indicating that it has low cytotoxicity.

[0044] The production of total ROS and superoxide anion O2 in cells under different control groups of the CMTJOIR hydrogel of this invention. ﹣ The occurrence of such situations is as follows Figure 12 B. It can be seen that the green fluorescence of the DCFH probe and the red fluorescence of the DHE probe in the control group CMCS-ATPP-Zn / TA@DS hydrogel were the weakest or even non-existent, indicating high ROS and O2 scavenging activity. ﹣ The ability.

[0045] 10. In vivo therapeutic experiments of CMTJOIR hydrogel: Figure 13 The photographs of the CMTJOIR hydrogel of this invention in different control groups on bacterial-infected skin wounds in rats illustrate that the hydrogel of this invention can promptly diagnose serious conditions during the wound healing process, reveal changes in inflammation, and enable timely and appropriate medication.

[0046] Figure 14 These are images showing the wound healing effects of the CMTJOIR hydrogel from this invention in different control groups. After successful modeling, the hydrogel was applied to the wound surface and treated with a laser therapy device (0.8 W / cm²). 2 Irradiation of the wound site showed a very good wound healing effect. Figure 14 A). Among them Figure 14 B is a schematic diagram showing the wound area healing rate of rats after different sample treatments on days 2, 4, 6, 8, and 10.

[0047] The above embodiments are only used to illustrate the technical solutions of the present invention, and are not intended to limit the present invention. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that any modifications, equivalent substitutions, and improvements made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A chitosan-based hydrogel, characterized in that, This chitosan-based hydrogel is obtained by crosslinking carboxymethyl chitosan with the crosslinking agent synthesized as shown in Formula 1. Formula 1.

2. The method for preparing a chitosan-based hydrogel according to claim 1, characterized in that, Includes the following steps: Step 1: Pyridine-2-carboxaldehyde and 4-(10,15,20-triphenylporphyrin-5-yl)aniline are heated under reflux in the presence of ethanol to obtain porphyrin Schiff base ligands; Step 2: Under nitrogen protection, IrCl3·3H2O and 4-(2-pyridyl)-benzaldehyde ligand are heated under reflux to obtain 4-(2-pyridyl)-benzaldehyde iridium dichlorobridge; Step 3: Under nitrogen protection, the 4-(2-pyridyl)-benzaldehyde iridium dichlorobridge from Step 2 and the porphyrin Schiff base ligand from Step 1 were placed in the dark and refluxed in the presence of a solvent. After the reaction was completed, potassium hexafluorophosphate was added and stirring was continued to obtain the metal iridium complex TJOIR shown in Formula 1. Step 4: Dissolve carboxymethyl chitosan CMCS and the metal iridium complex TJOIR shown in Formula 1 in a solvent, mix them, stir, and let stand at room temperature to obtain the chitosan-based hydrogel.

3. The method for preparing a chitosan-based hydrogel according to claim 2, characterized in that, The molar ratio of pyridine-2-carboxaldehyde to 4-(10,15,20-triphenylporphyrin-5-yl)aniline in step one is 2:

1.

4. The method for preparing a chitosan-based hydrogel according to claim 2, characterized in that, The reaction temperature in step one is 78-90 ℃, and the reaction time is 8-12 h.

5. The method for preparing a chitosan-based hydrogel according to claim 2, characterized in that, The reaction temperature in step two is 120℃-130℃, and the reaction time is 24-30 h.

6. The method for preparing a chitosan-based hydrogel according to claim 2, characterized in that, The molar ratio of IrCl3·3H2O and 4-(2-pyridyl)-benzaldehyde in step two is 1:(2.5-3).

7. The method for preparing a chitosan-based hydrogel according to claim 2, characterized in that, The reflux reaction in step three is carried out at a temperature of 75 ℃-90 ℃ for 8-12 h.

8. The method for preparing a chitosan-based hydrogel according to claim 2, characterized in that, The molar ratio of the 4-(2-pyridyl)-benzaldehyde iridium dichlorobridge and the porphyrin Schiff base ligand in step three is 1:

2.

9. The method for preparing a chitosan-based hydrogel according to claim 2, characterized in that, The mass ratio of CMCS to TJOIR in step four is 10:

1.

10. The use of the chitosan-based hydrogel according to claim 1 in the preparation of a wound healing drug for treating bacterial infections.

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