Mannose / trimethyl chitosan modified MXene material, preparation method and application in preventing and treating inflammatory bowel disease

Abstract

The invention relates to the technical field of medicines, and discloses a mannose / trimethyl chitosan modified MXene material (MTC / MXene), a preparation method and application of the mannose / trimethyl chitosan modified MXene material in prevention and treatment of inflammatory bowel diseases. The MTC / MXene material is obtained by preparing mannose-modified trimethyl chitosan and modifying the mannose-modified trimethyl chitosan on a single-layer MXene nanosheet, compared with a pure MXene material, MTC modification endows MXene with hydrophilicity, rich reaction sites are provided for drug loading, higher oxidation resistance is achieved, meanwhile, through surface functional groups and interlayer gaps of the MXene material, the MXene / MTC / MXene material can be used for preparing the drug, and the drug loading efficiency is improved. Different types of drug molecules are loaded and are used for realizing targeted delivery and controlled release of drugs.

Description

Technical Field

[0001] The present invention belongs to the technical field related to drug preparation, and specifically relates to the application of MXene materials. Background Art

[0002] Inflammatory bowel disease (IBD) is an autoimmune chronic inflammatory disease of the digestive system, including Crohn's disease (CD) and ulcerative colitis (UC). The disease is distributed worldwide and is also a serious threat to the health of the Chinese people. In recent years, with the improvement of people's living standards and changes in dietary structure, the incidence of this disease in my country has been increasing year by year. The etiology and detailed mechanisms of the occurrence and development of IBD are still unclear, and a complete cure is not yet possible. Long-term or even lifelong treatment is required. At present, immunosuppressants, immunomodulators and monoclonal antibodies are often used in the treatment of IBD and have certain effects, but most patients often have further activation of IBD due to side effects or drug failure. Therefore, finding truly effective targets can provide more treatment options for clinical patients.

[0003] In recent years, with the rapid development of nanomaterials and nanotechnology, research and application in the medical field involve drug carrier tools, disease diagnosis and treatment, etc. Nanomaterials have good biocompatibility and can specifically bind to biomacromolecules through interaction to form a function of targeting specific cells. Therefore, nanomaterials are used as non-viral carriers in biomedical and gene delivery research. Among them, chitosan is the only polycationic polysaccharide nanomaterial in nature. It can be combined with nucleic acids to form nanoparticles. It has low toxicity and biocompatibility. At the same time, it has the characteristics of easy structural modification and can effectively achieve gene delivery. Nanoparticles made of chitosan complexes have become a research hotspot in the fields of medicine, biochemistry and biomedical engineering as efficient carriers for carrying drugs and genes, and are widely used in the delivery of gene drugs. Although chitosan nanomaterials have many advantages, they dissolve poorly in neutral or alkaline conditions and cannot exist in an ionic state. Therefore, they lose the ability to promote the penetration and absorption of drugs or genes in mucosal sites. This chitosan is tightly bound to plasmid DNA, and the formed nanoparticles are difficult to dissociate in cells, resulting in low transfection efficiency. In order to make it more effectively used in gene carriers, chitosan derivatives are obtained by chemically modifying chitosan. The performance of these derivatives is significantly improved compared with chitosan. N-trimethyl chitosan (MTC) is an important type of chemically modified chitosan product. MTC has good solubility under different pH conditions and also has good bioadhesion. Even under neutral or alkaline conditions, it can still reduce the resistance formed across epithelial cells in intestinal tissues, open the tight junctions (Tight Junction, TJ) of the intestinal epithelium, and promote the penetration and absorption of drugs or genes in the mucosa. However, nanoparticles based on MTC as a carrier lack active targeting to target cells, and ligand modification of trimethyl chitosan nanocarriers is required to exert specific targeting functions.

[0004] Patent CN105396140A discloses an anti-tumor immunotherapy nano drug delivery system and its construction method. It uses anionic cyclodextrin-DNA and mannose-modified trimethyl chitosan drug delivery system when constructing gene therapy. It mentions that immature dendritic cells (DC) have antigen presentation function. In fact, DC cells also have the function of inflammatory response. Under infection or inflammatory conditions, immature dendritic cells can release pro-inflammatory cytokines, such as IL-1, IL-6, TNF-α, etc., to promote local inflammatory response and recruit other immune cells to participate in immune defense. However, due to the complex environment of intestinal inflammation, there are certain difficulties in using DNA and mannose-modified trimethyl chitosan. The main factors are as follows: 1. The human digestive system is a complex network that starts from the mouth, passes through the esophagus, stomach, small intestine, large intestine, and finally reaches the rectum and anus. The pH value and physical and chemical environment of different parts will vary with the changes in the digestive process.

[0005] 2. When passing through the gastric environment, because it contains a large amount of hydrochloric acid, the gastric acid environment (pH is about 1-2) has strong oxidizing properties. This acidic condition can destroy bacteria and other pathogens, but it is a greater challenge for the drug delivery system. Summary of the invention

[0006] MXene is an emerging type of two-dimensional material. This type of material is composed of transition metal carbides, nitrides or carbonitrides with a thickness of several atomic layers. MXene has the following excellent properties: First, the functional groups on the surface of MXene materials (such as -OH, -COOH, etc.) make them biocompatible. These functional groups can interact with molecules in the body, reduce cytotoxicity, and make MXene safe to use in biomedical applications; Secondly, MXene materials have a large specific surface area, which allows them to carry a large amount of drugs or other bioactive molecules. Therefore, MXene can be used as an efficient drug carrier for precise drug delivery, improving therapeutic effects and reducing side effects; Third, the layered structure of MXene can be regulated by chemical means, making the release of drugs more controllable. Combined with the pH responsiveness of MXene, a smart drug release system that responds to changes in the external environment can be designed; Fourth, the functional groups on the surface of MXene materials (such as -OH, -COOH, etc.) can react with oxidants to play an antioxidant role; In view of the above-mentioned MXene properties, the present invention intends to use MXene materials as the main carrier of the present invention, and to construct a drug delivery system for preventing and treating inflammatory bowel disease.

[0007] The present invention obtains mannose / trimethyl chitosan modified MXene material by modifying mannose / trimethyl chitosan on MXene material and discloses a preparation method. Another aspect of the present invention is based on the application of this material in preventing and treating inflammatory bowel disease.

[0008] The method for preparing MXene materials modified with mannose / trimethyl chitosan comprises the following steps: Step 1: Preparation of mannose-modified trimethyl chitosan: Under nitrogen environment, mannosamine hydrochloride was dissolved and desalted with triethylamine to obtain mannosamine solution, which was then slowly added to trimethyl chitosan solution. After the addition was completed, the reaction was continued to complete. The reaction solution was dialyzed in DMF for two days (MWCO was 5000-7000 Da), and then dialyzed in DCM. Finally, it was precipitated twice in 30 to 40 volumes of ice ether, filtered, and vacuum dried to obtain mannose-modified trimethyl chitosan; Step 2: Preparation of single-layer MXene nanosheet dispersion: Slowly dissolve LiF in 6-12M hydrochloric acid, stir for 10 minutes to fully dissolve it, slowly add MAX phase material, stir until fully dissolved, first wash with 1M dilute hydrochloric acid to remove excess lithium fluoride. Then wash with deionized water and centrifuge at a speed of 2000-3500 rpm, centrifuge for 5 minutes each time, centrifuge about 6-8 times, make the pH of the solution greater than 6, collect the precipitate, and dissolve it in water, perform ultrasonic dispersion under argon protection atmosphere, and finally centrifuge at 2000-3500 rpm for 30-60 minutes, collect the supernatant, and obtain a monolayer MXene dispersion; Step 3: Mannose / trimethyl chitosan modification of MXene: The mannose-modified trimethyl chitosan obtained in step 1 was dissolved in DMF, and the monolayer MXene dispersion prepared in step 2 was added. The temperature was below 40 degrees, and then stirred in a nitrogen atmosphere for 24-48 hours. After centrifugation and washing, the mannose / trimethyl chitosan modified MXene material was obtained after freeze-drying.

[0009] Among them, the single-layer MXene nanosheet can be selected from vanadium-based MXene materials (V2C), niobium-based MXene materials (Nb2C), tantalum-based MXene materials (Ta4C3), molybdenum-based MXene materials (Mo2C), chromium-based MXene materials (Cr2C), and nitrides or carbonitrides of the above materials.

[0010] Preferably, the MAX phase material is selected from Ti3AlC2, Ti3SiC2, Ti2AlC, Cr2AlC, V2AlC, Mo2TiC2, Ti3GeC2, Ti3VC2, Ti3SiN2, and Ti2AlN, preferably Ti3AlC2.

[0011] Wherein, the mannosamine hydrochloride adopts D-mannosamine hydrochloride.

[0012] On the other hand, the present invention discloses a mannose / trimethyl chitosan modified MXene material, which is based on a D-mannose / trimethyl chitosan modified MXene material, wherein the precursor MAX phase material of the MXene material is selected from one of Ti3AlC2, Ti3SiC2, Ti2AlC, Cr2AlC, V2AlC, Mo2TiC2, Ti3GeC2, Ti3VC2, Ti3SiN2, and Ti2AlN.

[0013] The present invention also discloses the application of MXene materials modified by mannose / trimethyl chitosan in preventing and treating inflammatory bowel disease.

[0014] The beneficial effects of the present invention are as follows: 1. The present invention constructs a gene nanocarrier targeting intestinal macrophages by performing MTC modification on a two-dimensional MXene material, which has good antioxidant properties and high targeting.

[0015] 2. Functional groups on the surface of MXene materials The functional groups on the surface (such as -OH, -COOH, etc.) make it have good biocompatibility.

[0016] 3. The layered structure of MXene can be regulated by chemical means, making the release of drugs more controllable. Combined with the pH responsiveness of MXene, an intelligent drug release system that responds to changes in the external environment can be designed, providing a path for further optimizing the drug delivery system. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] Figure 1 This is a SEM comparison diagram of MXene before and after modification in Example 1; Figure 2 XRD test diagram of MXene before and after modification in Example 1; Figure 3 This is the AFM atomic force microscope image of Example 1; Figure 4 This is the EPR test result diagram of MXene nanozyme before and after MXene modification in Example 1; Figure 5 This is a comparison diagram of the enzyme activity simulation of MXene nanozyme before and after MXene modification in Example 1; Figure 6 The FITC fluorescence result of the cell targeting experiment in Example 1; Figure 7 The following are the results of HE staining of the histological analysis of the mice in Example 1. DETAILED DESCRIPTION

[0018] In order to better understand the present invention, the present invention is further described below in conjunction with specific examples, wherein the terms used in the examples are for describing specific embodiments and do not constitute limitations on the scope of protection of the present invention. Example 1

[0019] Step 1. Mannose-modified trimethyl chitosan: Under nitrogen environment, D-mannosamine hydrochloride (24 mg) was dissolved and desalted with triethylamine (22.5 mg) to obtain D-mannosamine solution, which was then slowly added dropwise to trimethyl chitosan solution. After the addition was completed, the reaction was continued for 48 hours. The reaction solution was dialyzed in DMF for two days (MWCO 7000 Da) and DCM for one day, and finally precipitated twice in 30 volumes of ice ether, filtered, and vacuum dried for 24 hours to obtain mannose-modified trimethyl chitosan.

[0020] Step 2. Preparation of single-layer MXene nanosheet dispersion: 2.0 g LiF was slowly dissolved in 40 mL of 9M hydrochloric acid, stirred for 10 minutes to fully dissolve, and 1 g Ti3AlC2 was slowly added, stirred at 40 degrees Celsius for 24 hours (or 48 hours), and first washed twice with dilute hydrochloric acid (1M) to remove excess lithium fluoride. Then it was washed with deionized water and centrifuged at a speed of 3500 rpm, each centrifugation for 5 minutes, and about 6-8 centrifugations to make the pH of the solution greater than 6. The precipitate was collected and dissolved in 100 mL of water, and ultrasonicated for 2 hours in an argon atmosphere (power*time is about 360W*h). Finally, centrifuged at 3500 rpm for 30 minutes, and the supernatant was collected to obtain a monolayer MXene dispersion with a concentration of 5 mg / ml.

[0021] Step 3. Mannose / trimethyl chitosan modification of MXene: Take 0.1g of mannose-modified trimethyl chitosan in step 1 and dissolve it in 100ml DMF, add 100mL of the monolayer MXene dispersion prepared in step 2, stir for 24 hours in a nitrogen atmosphere at 40 degrees, centrifuge and wash, and freeze-dry to obtain mannose / trimethyl chitosan modified MXene material. For related experimental results, refer to Figures 1 to 5 ,The specific result review results are shown below.

[0022] Step 4. Targeted outcome testing: Construction of IBD model: 2.5% DSS (dextran sulfate sodium) was fed to mice for 5 days. DSS (Dextran Sulfate Sodium) is a chemical commonly used to construct mouse inflammatory bowel disease (IBD) model. DSS simulates the symptoms of human IBD, such as ulcerative colitis (UC), by causing damage and inflammatory response to the mouse colon mucosa.

[0023] Grouping: 30 mice were divided into three groups: DSS group (2.5% DSS gavage once a day), DSS+Water (2.5% DSS+water gavage 100ul once a day), DSS+MTC-MXene (2.5% DSS+25mg / kg dissolved in 100ul Water gavage once a day). The DSS+MTC-MXene group was gavaged with the MTC / MXene material obtained in step 3.

[0024] Stop DSS processing: Stop DSS on Day 5: Stop DSS treatment on Day 5 and allow mice to resume normal drinking water.

[0025] HE analysis: On the 7th day, the colon tissue of mice was taken for HE analysis: On the 7th day, the colon tissue of mice was taken for HE staining analysis to evaluate the degree of inflammation and histological changes of colon tissue. The specific process is as follows: Intraperitoneal anesthesia with sodium pentobarbital (1% sodium pentobarbital, 0.4-0.5ml / 100g body weight); intestinal tissue was collected, made into onion rolls, added with paraformaldehyde fixative (4℃, 24h), added with 20% sucrose (sucrose + 0.01M PBS), and sank to the bottom (4℃); 30% sucrose sank to the bottom (4℃, 12h), and then 30% sucrose sank to the bottom again (4℃, 12h); the material was taken out and the surface was dried (4℃, 10min), the material was placed in a mold and immersed in OTC (4℃, 10min), and sliced ​​(7μm thick); anti-slip glass slides, mounted, and dried in the dark at room temperature (about 12h); the slices treated with acetone and air-dried were rinsed in PBS in the dark for 3×10min, 0.3% Trion-100 solution at 37℃ for 10min×3 times, PBS in the dark for 5min×3 times, and blocked with 10% normal donkey serum for 30 min, and incubate overnight at 4°C with anti-rabbit source (F4 / 80). Rinse with PBS for 10 min × 3 times in the dark, use donkey anti-rabbit -Tex-Red (red) fluorescent secondary antibody at room temperature for 1 hour, and wash with PBS for 10 min × 4 times. Dry, directly add anti-quenching agent to seal the slide, and finally take pictures with an upright fluorescence microscope. For related experimental results, refer to Figure 6 and Figure 7 ,The specific result review results are shown below.

[0026] like Figure 1 The following is a comparison of scanning electron microscope images. The left image is the control group (single-layer MXene nanosheet dispersion prepared in step 2), and the right image is the experimental group (MTC / MXene material prepared in step 3). It can be seen that the surface of the unmodified pure MXene nanosheet is smooth, while there are many nanoparticles on the surface of MTC / MXene. This shows that the MTC / MXene material was successfully prepared in step 3.

[0027] Figure 2 This is the XRD test diagram. The MXene materials before and after modification (i.e., the single-layer MXene nanosheet prepared in step 2 and the MTC / MXene material prepared in step 3) have (002) characteristic peaks near 8 degrees, proving their layered structure. At the same time, the modification did not change their morphology. This shows that the MXene material basis of the MXene material modified with mannose / trimethyl chitosan has not changed after step 3.

[0028] Figure 3 This is an AFM atomic force microscope image, from which we can see that the thickness of a single-layer MXene nanosheet is only 1.75nm, proving that two-dimensional MXene nanosheets have been successfully synthesized. This shows that the MXene material basis of the MXene material modified with mannose / trimethyl chitosan in step 3 has not changed, and the two-dimensional morphological structure has been maintained.

[0029] Figure 4 This is the EPR test result of MXene nanozyme before and after modification (i.e., the single-layer MXene nanosheet prepared in step 2 and the MTC / MXene material prepared in step 3). The current parameters for characterizing antioxidant activity mainly include: 1. The difficulty of peroxyl radicals abstracting hydrogen from antioxidants; 2. The stability of antioxidant free radicals after the hydrogen abstraction reaction. Related research on antioxidant activity usually adopts qualitative methods or semi-quantitative control methods through EPR, that is, using EPR technology to measure the changes in free radical signals, and then the free radical concentration can be intuitively seen, thereby judging the ability of antioxidants to scavenge free radicals. Such as Figure 4 As shown, the free radical signal intensity of MTC / MXene is lower, indicating that MTC / MXene has stronger free radical scavenging ability and antioxidant capacity.

[0030] Figure 5The following is a comparison of the enzyme activity simulations of MXene nanozymes before and after modification (i.e., the monolayer MXene nanosheets prepared in step 2 and the MTC / MXene materials prepared in step 3). Disturbance of the skin oxidation-antioxidant system plays an important role in the pathogenesis of inflammatory skin diseases. Complex intracellular antioxidant systems, such as antioxidant enzymes, can inhibit ROS generation, maintain redox homeostasis, and prevent oxidative stress-induced cell damage. MXene materials have long been widely used in various biomedical fields because they have a variety of enzyme-like activities, such as peroxidase (POD), SOD, and CAT. Using H2O2 as a representative of reactive oxygen species, the scavenging activity of pure MXene and mannose / trimethyl chitosan-modified MXene materials on reactive oxygen species was evaluated. The modified MXene materials exhibited high ROS scavenging activity in a concentration-dependent manner. When the modified MXene was 400 μg / mL, about 90% of hydrogen peroxide was degraded. However, only about 68% of hydrogen peroxide was degraded by 400 μg / mL pure MXene. As the concentration of MXene nanozymes increased, the amount of formazan formed decreased significantly, indicating that the modified MXene nanozymes had more efficient superoxide dismutase (SOD)-like activity.

[0031] Figure 6 This is the result of the intestinal macrophage targeting test experiment of the DSS+MTC-MXene group in step 4. The macrophages were stained with F4 / 80, and the MXene material modified with mannose / trimethyl chitosan was modified with FITC fluorescence. Combined with DAPI, the co-localization results using the Merge technology showed that the MXene material modified with mannose / trimethyl chitosan with FITC fluorescence had appeared in the cells, indicating that the targeting was successful.

[0032] Figure 7 This is the histological analysis of different mice. Based on the content in the figure, the following results can be analyzed: 1. DSS group (treated with DSS only) result: 1. Severe inflammatory response: There is obvious infiltration of inflammatory cells in the colon tissue, especially infiltration of neutrophils and macrophages.

[0033] 2. Mucosal damage: ulcers, bleeding, and epithelial cell shedding occur in the colon mucosa.

[0034] 3. Reduced mucosal thickness: The colon mucosa becomes thinner and the glandular structure is disordered; 2. DSS + Water group (treated with DSS and gavaged with water) result: 1. Inflammatory response similar to that in the DSS group: Colonic tissue showed inflammatory cell infiltration and mucosal damage similar to that in the DSS group.

[0035] 2. Slight difference in inflammatory response: Since intragastric water has a certain effect on inflammation, the inflammatory response is milder than that in the DSS group, and the ulcers and bleeding in the colon mucosa are reduced, but the colon mucosa becomes thinner, the glandular structure is disordered, and the overall degree of inflammation is still high.

[0036] 3. DSS + MTC-MXene group (treated with DSS and intragastric administration of MTC-MXene) result: 1. Reduced inflammatory response: The inflammatory cell infiltration of colon tissue is reduced, manifested as less neutrophil and macrophage infiltration.

[0037] 2. Reduced mucosal damage: The degree of damage to the colon mucosa is reduced, ulcers and bleeding are reduced, and epithelial cell shedding is weakened.

[0038] 3. Increased mucosal thickness: The thickness of the colon mucosa has increased, and the glandular structure is more orderly.

[0039] Based on the specific implementation process of the above embodiments and in combination with the accompanying drawings, it can be explained that: 1. The experimental steps of Example 1 can successfully synthesize mannose / trimethyl chitosan modified MXene materials. Compared with general MXene materials, this material has stronger free radical scavenging ability and antioxidant ability, and has more efficient superoxide dismutase (SOD)-like activity.

[0040] 2. Able to successfully construct gene nanocarriers targeting intestinal macrophages with good targeting properties.

[0041] 3. HE analysis was used to demonstrate the effectiveness of mannose / trimethylchitosan modified MXene materials in preventing and treating inflammatory bowel disease. Example 2

[0042] Step 1. Mannose-modified trimethyl chitosan: Under nitrogen environment, D-mannosamine hydrochloride (30 mg) was dissolved and desalted with triethylamine (35 mg) to obtain D-mannosamine solution, which was then slowly added dropwise to the trimethyl chitosan solution. After the addition was completed, the reaction was continued for 40 hours. The reaction solution was dialyzed in DMF for 3 days (MWCO 5000 Da) and DCM for 2 days, and finally precipitated twice in 40 volumes of ice ether, filtered, and vacuum dried for 24 hours to obtain mannose-modified trimethyl chitosan.

[0043] Step 3. Preparation of single-layer MXene nanosheet dispersion: 1.0 g LiF was slowly dissolved in 20 mL of 9M hydrochloric acid, stirred for 10 minutes to fully dissolve, and 1 g Ti3AlC2 was slowly added. Stirred at 40 degrees Celsius for 48 hours. First, it was washed twice with dilute hydrochloric acid (1M) to remove excess lithium fluoride. Then it was washed with deionized water and centrifuged at a speed of 4000 rpm, each centrifugation for 5 minutes, and about 6-8 centrifugations to make the pH of the solution greater than 6. The precipitate was collected and dissolved in 100 mL of water. In an argon atmosphere, it was ultrasonicated for 4 hours (power*time was about 360 W*h). Finally, it was centrifuged at 3500 rpm for 40 minutes, and the supernatant was collected to obtain a monolayer MXene dispersion with a concentration of 8 mg / ml.

[0044] Step 3. Mannose / trimethyl chitosan modification of MXene: Take 0.2 g of mannose-modified trimethyl chitosan in step 1 and dissolve it in 200 ml of DMF, add 80 mL of the monolayer MXene dispersion prepared in step 2, stir for 36 hours in a nitrogen atmosphere at 40 degrees, centrifuge and wash, and freeze-dry to obtain the mannose / trimethyl chitosan modified MXene material. Example 3

[0045] Step 1. Mannose-modified trimethyl chitosan: Under nitrogen environment, D-mannosamine hydrochloride (30 mg) was dissolved and desalted with triethylamine (35 mg) to obtain D-mannosamine solution, which was then slowly added dropwise to the trimethyl chitosan solution. After the addition was completed, the reaction was continued for 40 hours. The reaction solution was dialyzed in DMF for 3 days (MWCO 5000 Da) and DCM for 2 days, and finally precipitated twice in 40 volumes of ice ether, filtered, and vacuum dried for 24 hours to obtain mannose-modified trimethyl chitosan.

[0046] Step 2. Preparation of single-layer MXene nanosheet dispersion: 2.0 g LiF was slowly dissolved in 30 mL of 9M hydrochloric acid, stirred for 10 minutes to fully dissolve, and 1 g Ti3AlC2 was slowly added. Stirred at 40 degrees Celsius for 64 hours. First, it was washed twice with dilute hydrochloric acid (1M) to remove excess lithium fluoride. Then it was washed with deionized water and centrifuged at a speed of 5000 rpm, each centrifugation for 5 minutes, and about 6-8 centrifugations to make the pH of the solution greater than 6. The precipitate was collected and dissolved in 100 mL of water. In an argon-protected atmosphere, it was ultrasonicated for 4 hours (power*time was about 360 W*h). Finally, it was centrifuged at 3500 rpm for 60 minutes, and the supernatant was collected to obtain a monolayer MXene dispersion with a concentration of 8 mg / ml.

[0047] Step 3. Mannose / trimethyl chitosan modification of MXene: Take 0.2 g of mannose-modified trimethyl chitosan in step 1 and dissolve it in 150 ml of DMF, add 50 mL of the monolayer MXene dispersion prepared in step 2, stir for 48 hours in a nitrogen atmosphere at 40 degrees, centrifuge and wash, and freeze-dry to obtain the mannose / trimethyl chitosan modified MXene material.

[0048] In the examples, the experimental methods used are conventional methods unless otherwise specified, and the materials, reagents, etc. used are all commercially available unless otherwise specified.

[0049] The above detailed description is a specific description of one of the feasible embodiments of the present invention. This embodiment is not intended to limit the patent scope of the present invention. Any equivalent implementation or change that does not deviate from the present invention should be included in the scope of the technical solution of the present invention. Of course, the above is only a typical example of the present invention. In addition, the present invention can also have many other specific implementation methods. Any technical solution formed by equivalent replacement or equivalent transformation falls within the scope of protection required by the present invention.

Claims

1. A method for preparing MXene materials modified with mannose / trimethyl chitosan, characterized in that: The steps include: Step 1: Preparation of mannose-modified trimethyl chitosan: Under nitrogen environment, mannosamine hydrochloride was dissolved and desalted with triethylamine to obtain mannosamine solution, which was then slowly added to trimethyl chitosan solution. After the addition was completed, the reaction was continued to complete. The reaction solution was dialyzed in DMF for two days (MWCO was 5000-7000 Da), and then dialyzed in DCM. Finally, it was precipitated twice in 30 to 40 volumes of ice ether, filtered, and vacuum dried to obtain mannose-modified trimethyl chitosan; Step 2: Preparation of single-layer MXene nanosheet dispersion: Slowly dissolve LiF in 6-12M hydrochloric acid, stir for 10 minutes to fully dissolve it, slowly add MAX phase material, stir until fully dissolved, first wash with 1M dilute hydrochloric acid to remove excess lithium fluoride. Then wash with deionized water and centrifuge at a speed of 2000-3500 rpm, centrifuge for 5 minutes each time, centrifuge about 6-8 times, make the pH of the solution greater than 6, collect the precipitate, and dissolve it in water, perform ultrasonic dispersion under argon protection atmosphere, and finally centrifuge at 2000-3500 rpm for 30-60 minutes, collect the supernatant, and obtain a monolayer MXene dispersion; Step 3: Mannose / trimethyl chitosan modification of MXene: The mannose-modified trimethyl chitosan obtained in step 1 was dissolved in DMF, and the monolayer MXene dispersion prepared in step 2 was added. The temperature was below 40 degrees, and then stirred in a nitrogen atmosphere for 24-48 hours. After centrifugation and washing, the mannose / trimethyl chitosan modified MXene material was obtained after freeze-drying.

2. The method for preparing the MXene material modified with mannose / trimethyl chitosan according to claim 1, characterized in that: The single-layer MXene nanosheets can be selected from vanadium-based MXene materials (V2C), niobium-based MXene materials (Nb2C), tantalum-based MXene materials (Ta4C3), molybdenum-based MXene materials (Mo2C), chromium-based MXene materials (Cr2C), and nitrides or carbonitrides of the above materials.

3. The method for preparing the MXene material modified with mannose / trimethyl chitosan according to claim 2, characterized in that: The MAX phase material is selected from one of Ti3AlC2, Ti3SiC2, Ti2AlC, Ti3GeC2, Ti3VC2, Ti3SiN2, and Ti2AlN.

4. The method for preparing the mannose / trimethyl chitosan modified MXene material according to claim 1, characterized in that: The mannosamine hydrochloride is D-mannosamine hydrochloride.

5. Mannose / trimethyl chitosan modified MXene material, characterized by: It is a MXene material modified with D-mannose / trimethyl chitosan.

6. An application for preventing and treating inflammatory bowel disease, characterized in that: It adopts the preparation method of the mannose / trimethyl chitosan modified MXene material as described in claims 1-4.

7. An application for preventing and treating inflammatory bowel disease, characterized in that: It uses the mannose / trimethyl chitosan modified MXene material as described in claim 5.

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