Anionic polymer grafted covalent organic framework material and preparation method and application thereof

Abstract

The present invention provides an anionic polymer grafted covalent organic framework material and a preparation method and application thereof. The covalent organic framework material COF-V is synthesized by polymerizing 1,3,5-tri(4-aminophenyl)benzene and 2,5-divinyl-1,4-phthalaldehyde, and polymer hair is grafted on the surface of COF-V using 2-acrylamido-2-methyl-1-propanesulfonic acid as a monomer to obtain a novel covalent organic framework molecular brush COF- g ‑PAMPS. COF‑ g On the one hand, ‑PAMPS has the high chemical stability of COF‑V materials and can resist gastric acid, making it suitable as a drug delivery platform for oral drugs; on the other hand, it can carry a negative charge in aqueous solution and has the characteristics of mucosal adhesion and receptor interaction when used as a drug delivery platform, which is conducive to adhering to the positively charged inflamed colon mucosal surface and targeted release of drugs.

Description

Technical Field

[0001] The present invention relates to the field of organic materials, and more specifically to an anionic polymer grafted covalent organic framework material and a preparation method and application thereof. Background Art

[0002] Inflammatory bowel disease (IBD), characterized by chronic inflammatory disease of the colon, is common and prevalent. Ulcerative colitis (UC) and Crohn's disease (CD), the two main types of IBD, present with severe intestinal disease, including diarrhea, abdominal pain, weight loss, and bloody stools. IBD-associated immune responses are triggered by intestinal components, especially the gut microbiota, which are suspected to contribute to susceptibility to CD and UC. Both human and animal studies have reported a potential role for an imbalance in the gut microbiota in the pathogenesis of IBD. Molecular and high-throughput sequencing analyses of the gut microbiota in IBD patients have revealed changes in a characteristic microbial signature, or dysbiosis, characterized by a disrupted balance between common gut probiotics and opportunistic pathogens, ultimately leading to a decrease in gut biodiversity.

[0003] At present, although traditional oral medications such as aminosalicylic acid preparations, glucocorticoids and immunosuppressants are effective in relieving UC, these drugs are not targeted when taken orally, have low drug utilization, poor effects, and can have a significant negative impact on the body. Therefore, it is necessary to establish a drug delivery platform that can resist the strong acidic environment of the stomach and the weak alkaline environment of the small intestine, and release drugs by targeting the inflamed colon epithelial cells to achieve precise drug release and improve drug utilization.

[0004] Covalent Organic Frameworks (COFs) are a type of two-dimensional or three-dimensional crystalline materials with a porous structure formed by organic units connected by covalent bonds. COFs have great application potential in drug delivery platforms due to their high specific surface area, adjustable structure and function, and good stability. However, the release accuracy and rate of most COFs-based drug delivery systems are difficult to control, the preparation cost is high, and it is difficult to achieve accurate and targeted drug delivery. Summary of the invention

[0005] The present invention aims to overcome at least one of the above-mentioned deficiencies of the prior art and provide an anionic polymer grafted covalent organic framework material and a preparation method and application thereof.

[0006] An object of the present invention is to provide a method for preparing an anionic polymer grafted covalent organic framework material, comprising the following steps:

[0007] S1. Dispersing 1 part of 1,3,5-tri(4-aminophenyl)benzene (monomer A) and 1-4 parts of 2,5-divinyl-1,4-benzenedicarbaldehyde (monomer B) in a first organic solvent according to a molar ratio to form a first monomer solution; then adding 90-500 parts of acetic acid to the first monomer solution, mixing, and reacting at room temperature and allowing to stand for precipitation;

[0008] S2. collecting the precipitate obtained by the reaction in step S1, washing and drying to obtain a covalent organic framework material COF-V;

[0009] S3. Take 5 parts of the COF-V and 50-100 parts of 2-acrylamido-2-methyl-1-propane sulfonic acid (monomer C) in a mass fraction ratio and disperse them in a second organic solvent to form a second monomer solution; add 1-1.5 parts of an initiator to the second monomer solution and react and precipitate under an inert atmosphere;

[0010] S4. Collect the precipitate obtained by the reaction in step S3, wash and dry it to obtain anionic polymer grafted covalent organic framework material COF- g -PAMPS.

[0011] In the technical scheme, a highly stable covalent organic framework material COF-V is formed by reacting and polymerizing monomers A and B under relatively mild synthesis conditions, and further, under the action of an initiator, monomer C is used to perform surface modification on the prepared COF-V. Specifically, monomer C is polymerized and grafted onto the surface of the prepared COF-V to synthesize COF- g -PAMPS materials make COF- g -PAMPS material has multiple sulfonic acid groups on its surface; since the sulfonic acid groups have dissociation in aqueous solution, the prepared COF- g -PAMPS has anionic surface charge in aqueous solution, which makes the prepared COF- g -PAMPS has the characteristics of high chemical stability of COF-V materials and can exhibit anionic surface charge in aqueous solution.

[0012] Furthermore, due to the prepared COF- g -PAMPS also has good structural stability in an acidic environment and can resist gastric acid, making it suitable for use as a drug delivery platform for small molecular weight oral drugs; further, due to the prepared COF- g-PAMPS can also carry a negative charge on its surface in aqueous solution, which makes it have mucosal adhesion and receptor interaction properties when used as a drug delivery platform. It can advantageously adhere to the cationic mucosal surface, making it suitable as a drug delivery platform for targeted release of drugs on the cationic mucosal surface, thereby prolonging the local availability of drugs and reducing the frequency of administration, while also preventing the systemic toxicity of drugs and ensuring the therapeutic effect of the drugs carried.

[0013] Preferably, the first organic solvent is acetonitrile or methanol; the concentration of the acetic acid is 12-20 M; and the reaction and precipitation time is 48-72 h.

[0014] Preferably, in step S1, the molar volume ratio of 1,3,5-tris(4-aminophenyl)benzene to the first organic solvent is not less than 1:100 mol / L.

[0015] Preferably, in step S2, the washing process is: washing the precipitate with tetrahydrofuran, and then washing with methanol or ethanol;

[0016] The vacuum drying time is 24-48 h.

[0017] Preferably, in step S3, the second organic solvent is selected from N,N-dimethylformamide or methanol;

[0018] The initiator is selected from azobisisobutyronitrile or dibenzoyl peroxide;

[0019] The process of the reaction under an inert atmosphere is: heating the second monomer solution after adding the initiator to 65-105° C. and reacting for 18-24 hours.

[0020] Preferably, in step S4, the washing process is: washing the second precipitate with pure water and then washing with methanol or ethanol;

[0021] The vacuum drying time is 24-48 h.

[0022] Preferably, in step S2 and step S4, the yellow precipitate and the brown-yellow precipitate are collected by centrifugation; in the centrifugation method, the rotation speed of the centrifuge is not less than 9000 rpm, and the centrifugation time is not less than 4 min.

[0023] Preferably, in the step S1 and the step S3, an ultrasonic dispersion method is used to form the first monomer solution and the second monomer solution; in the ultrasonic dispersion method, the ultrasonic time is not less than 1 min;

[0024] In the step S1, a rotary oscillator is used to oscillate for 10 seconds to mix the first monomer solution and the acetic acid.

[0025] Another object of the present invention is to provide an anionic polymer grafted covalent organic framework material prepared by the preparation method provided in the technical solution.

[0026] Another object of the present invention is to provide a drug system based on the anionic polymer grafted covalent organic framework material provided in the technical solution and applied to the treatment of inflammatory bowel disease. In inflammatory bowel disease, patchy inflammation of the intestinal epithelium has a disordered mucus layer, high concentrations of cationic proteins (such as transferrin, ferritin, bactericidal or permeability enhancing proteins, etc.) and accumulation of antimicrobial peptides, resulting in the accumulation of positive charges on the surface of colitis. Based on the COF- g -PAMPS constructed drug system can preferentially adhere to positively charged inflamed colon epithelial cells and slowly release the active ingredients in the drug system; at the same time, the drug system also has excellent structural stability in an acidic environment and can resist gastric acid. g -PAMPS constructed drug system, the drug active ingredients can be various drugs that have been proven to be effective in treating inflammatory bowel disease, through COF- g -PAMPS delivers drugs to inflamed colonic epithelial cells in a targeted manner, thereby prolonging the local availability of the above-mentioned active ingredients in the drug system and reducing the frequency of administration, while also preventing the systemic toxicity of the drug and ensuring the therapeutic effect of the drug.

[0027] Preferably, the active ingredients in the drug system for treating inflammatory bowel disease include one or more of small molecular weight oral drugs such as metformin, sodium salicylate, 5-aminosalicylic acid and glucocorticoids. As a small molecular weight drug with relatively low cost and superior safety, metformin has been shown to act on intestinal inflammation areas and increase the levels of Akkermansia muciniphila and Lactobacillus in the intestine, which have anti-inflammatory effects. Studies have shown that Akkermansia muciniphila and Lactobacillus are reduced in inflammatory bowel disease and negatively correlated with inflammation scores; at the same time, Akkermansia muciniphila and Lactobacillus also show potential benefits for IBD, with anti-inflammatory and intestinal barrier protection effects. Existing studies have also shown that intestinal microbiota has a significant impact on the mucus barrier, and intestinal microbiota and its bacterial products can regulate the secretion of mucin 2 by goblet cells, thereby achieving the regulatory properties of the mucus barrier. Therefore, metformin can exert its anti-inflammatory and mucus barrier protection effects in UC by regulating the intestinal microbiota. Using the COF- g -PAMPS is used to load metformin, COF- g-PAMPS carries an overall negative charge after entering the gastrointestinal tract, which can promote its adhesion to the positively charged inflamed colon epithelial cells, facilitate its local release of metformin at the site of inflammation, and help restore the normal intestinal microenvironment, thereby effectively treating UC.

[0028] Compared with the prior art, the present invention has the following beneficial effects:

[0029] 1. Monomer A and monomer B can be polymerized under mild synthetic conditions to form a highly stable covalent organic framework material COF-V, and further initiate polymerization of monomer C on its skeleton to achieve surface graft polymerization modification of COF-V to obtain COF- g -PAMPS new molecular brushes.

[0030] 2. Prepared COF- g -PAMPS has excellent structural stability in acidic environments and can resist gastric acid, making it suitable for use as a drug delivery platform for oral drugs;

[0031] 3. Prepared COF- g -PAMPS can also carry a negative charge in aqueous solution, which makes it have mucosal adhesion and receptor interaction properties when used as a drug delivery platform. It can advantageously adhere to the surface of positively charged inflamed colon epithelial cells and slowly release the active ingredients in the drug system.

[0032] 4. Through COF- g -When PAMPS is loaded with model drugs such as metformin, it can release metformin in a targeted manner at the site of inflammation, helping to restore the normal intestinal microenvironment and achieve anti-inflammatory and barrier protection effects. BRIEF DESCRIPTION OF THE DRAWINGS

[0033] Figure 1 The anionic polymer grafted covalent organic framework material COF- g -Schematic diagram of the preparation process of PAMPS.

[0034] Figure 2 The covalent organic framework material COF-V prepared in Example 1 of the present invention is grafted with an anionic polymer covalent organic framework material COF- g -Physical picture of PAMPS.

[0035] Figure 3 The covalent organic framework material COF-V prepared in Example 1 of the present invention is grafted with an anionic polymer covalent organic framework material COF- g -Infrared spectrum of PAMPS.

[0036] Figure 4The covalent organic framework material COF-V prepared in Example 1 of the present invention is grafted with an anionic polymer covalent organic framework material COF- g -XRD spectrum of PAMPS.

[0037] Figure 5 The anionic polymer grafted covalent organic framework material COF- g -SEM comparison of PAMPS before and after immersion in gastric juice and intestinal juice for 6 hours.

[0038] Figure 6 The covalent organic framework material COF-V prepared in Example 1 of the present invention is grafted with an anionic polymer covalent organic framework material COF- g -PAMPS, COF- after being immersed in gastric and intestinal fluid for 6 hours g -PAMPS (sp-COF- g Zeta potential diagram of PAMPs.

[0039] Figure 7 The COF-10 loaded with metformin provided in Example 12 of the present invention g -Drug release capability verification diagram of PAMPS drug system. DETAILED DESCRIPTION

[0040] The drawings of the present invention are only for illustrative purposes and should not be construed as limiting the present invention. In order to better illustrate the following embodiments, some parts of the drawings may be omitted, enlarged or reduced, and do not represent the size of the actual product; it is understandable to those skilled in the art that some well-known structures and their descriptions in the drawings may be omitted.

[0041] Example 1

[0042] like Figure 1 As shown, this embodiment provides an anionic polymer grafted covalent organic framework material COF- g -PAMPS preparation method, the preparation process is as follows:

[0043] S1. Add 14 mg of monomer A and 11.16 mg of monomer B to a centrifuge tube. Then, add 5 mL of acetonitrile to the centrifuge tube and sonicate the mixture for 1 minute to completely dissolve the monomers. Then add 0.4 mL of 12 M acetic acid to the centrifuge tube, shake vigorously on a rotary shaker for 10 s, and let stand at room temperature for 72 h.

[0044] S2. The yellow precipitate was collected by centrifugation at 9500 rpm for 5 min, washed three times with tetrahydrofuran and ethanol respectively, and dried in a vacuum drying oven for 24 h to obtain the covalent organic framework material COF-V.

[0045] S3. Add 100 mg of COF-V and 1000 mg of monomer C into an eggplant-shaped bottle containing N,N-dimethylformamide and disperse them by ultrasonication for 2 min. Then add 20 mg of initiator azobisisobutyronitrile and heat to 65 °C in a nitrogen environment for 18 h.

[0046] S4. The brown-yellow precipitate was collected by centrifugation at 9500 rpm for 5 min, washed three times with pure water and ethanol respectively, and then dried in a vacuum drying oven for 24 h to obtain the anionic polymer grafted covalent organic framework material COF-g-PAMPS.

[0047] Example 2

[0048] like Figure 1 As shown, this embodiment also provides an anionic polymer grafted covalent organic framework material COF- g -PAMPS preparation method, the preparation process is as follows:

[0049] S1. Add 14 mg of monomer A and 11.16 mg of monomer B to a centrifuge tube. Then, add 10 mL of acetonitrile to the centrifuge tube and sonicate the mixture for 1 minute to completely dissolve the monomers. Then add 0.4 mL of 12 M acetic acid to the centrifuge tube, shake vigorously on a rotary shaker for 10 s, and let stand at room temperature for 72 h.

[0050] S2. The yellow precipitate was collected by centrifugation at 9500 rpm for 5 min, washed three times with tetrahydrofuran and ethanol respectively, and dried in a vacuum drying oven for 24 h to obtain the covalent organic framework material COF-V.

[0051] S3. Add 100 mg of COF-V and 1000 mg of monomer C into an eggplant-shaped bottle containing N,N-dimethylformamide and disperse them by ultrasonication for 2 min. Then add 20 mg of initiator azobisisobutyronitrile and heat to 65 °C in a nitrogen environment for 18 h.

[0052] S4, the brown-yellow precipitate was collected by centrifugation at 9500 rpm for 5 min, and washed three times with pure water and ethanol respectively, and then dried in a vacuum drying oven for 24 h to obtain anionic polymer grafted covalent organic framework material COF- g -PAMPS.

[0053] Example 3

[0054] like Figure 1 As shown, this embodiment also provides an anionic polymer grafted covalent organic framework material COF- g -PAMPS preparation method, the preparation process is as follows:

[0055] S1. Add 14 mg of monomer A and 24.3 mg of monomer B to a centrifuge tube. Then, add 5 mL of acetonitrile to the centrifuge tube and sonicate the mixture for 1 minute to completely dissolve the monomers. Then add 1 mL of 20 M acetic acid to the centrifuge tube, shake vigorously on a rotary shaker for 10 s, and let stand at room temperature for 72 h.

[0056] S2. The yellow precipitate was collected by centrifugation at 9500 rpm for 5 min, washed three times with tetrahydrofuran and ethanol respectively, and dried in a vacuum drying oven for 24 h to obtain the covalent organic framework material COF-V.

[0057] S3. Add 100 mg of COF-V and 1000 mg of monomer C into an eggplant-shaped bottle containing N,N-dimethylformamide and disperse them by ultrasonication for 2 min. Then add 20 mg of initiator azobisisobutyronitrile and heat to 65 °C in a nitrogen environment for 18 h.

[0058] S4, the brown-yellow precipitate was collected by centrifugation at 9500 rpm for 5 min, and washed three times with pure water and ethanol respectively, and then dried in a vacuum drying oven for 24 h to obtain anionic polymer grafted covalent organic framework material COF- g -PAMPS.

[0059] Example 4

[0060] like Figure 1 As shown, this embodiment also provides an anionic polymer grafted covalent organic framework material COF- g -PAMPS preparation method, the preparation process is as follows:

[0061] S1. Add 14 mg of monomer A and 11.16 mg of monomer B to a centrifuge tube. Then, add 5 mL of methanol to the centrifuge tube and sonicate the mixture for 1 minute to completely dissolve the monomers. Then add 0.4 mL of 12 M acetic acid to the centrifuge tube, shake vigorously on a rotary shaker for 10 s, and let stand at room temperature for 72 h.

[0062] S2. The yellow precipitate was collected by centrifugation at 9500 rpm for 5 min, washed three times with tetrahydrofuran and ethanol respectively, and dried in a vacuum drying oven for 24 h to obtain the covalent organic framework material COF-V.

[0063] S3. Add 100 mg of COF-V and 1000 mg of monomer C into an eggplant-shaped bottle containing N,N-dimethylformamide and disperse them by ultrasonication for 2 min. Then add 20 mg of initiator azobisisobutyronitrile and heat to 65 °C in a nitrogen environment for 18 h.

[0064] S4, the brown-yellow precipitate was collected by centrifugation at 9500 rpm for 5 min, and washed three times with pure water and ethanol respectively, and then dried in a vacuum drying oven for 24 h to obtain anionic polymer grafted covalent organic framework material COF- g -PAMPS.

[0065] Example 5

[0066] like Figure 1 As shown, this embodiment also provides an anionic polymer grafted covalent organic framework material COF- g -PAMPS preparation method, the preparation process is as follows:

[0067] S1. Add 14 mg of monomer A and 11.16 mg of monomer B to a centrifuge tube. Then, add 5 mL of acetonitrile to the centrifuge tube and sonicate the mixture for 1 minute to completely dissolve the monomers. Then add 0.4 mL of 12 M acetic acid to the centrifuge tube, shake vigorously on a rotary shaker for 10 s, and let stand at room temperature for 48 h.

[0068] S2. The yellow precipitate was collected by centrifugation at 9500 rpm for 5 min, washed three times with tetrahydrofuran and ethanol respectively, and dried in a vacuum drying oven for 24 h to obtain the covalent organic framework material COF-V.

[0069] S3. Add 100 mg of COF-V and 1000 mg of monomer C into an eggplant-shaped bottle containing N,N-dimethylformamide and disperse them by ultrasonication for 2 min. Then add 20 mg of initiator azobisisobutyronitrile and heat to 65 °C in a nitrogen environment for 18 h.

[0070] S4, the brown-yellow precipitate was collected by centrifugation at 9500 rpm for 5 min, and washed three times with pure water and ethanol respectively, and then dried in a vacuum drying oven for 24 h to obtain anionic polymer grafted covalent organic framework material COF- g-PAMPS.

[0071] Example 6

[0072] like Figure 1 As shown, this embodiment also provides an anionic polymer grafted covalent organic framework material COF- g -PAMPS preparation method, the preparation process is as follows:

[0073] S1. Add 14 mg of monomer A and 11.16 mg of monomer B to a centrifuge tube. Then, add 5 mL of acetonitrile to the centrifuge tube and sonicate the mixture for 1 minute to completely dissolve the monomers. Then add 0.4 mL of 12 M acetic acid to the centrifuge tube, shake vigorously on a rotary shaker for 10 s, and let stand at room temperature for 72 h.

[0074] S2. The yellow precipitate was collected by centrifugation at 9500 rpm for 5 min, washed three times with tetrahydrofuran and methanol respectively, and dried in a vacuum drying oven for 24 h to obtain the covalent organic framework material COF-V.

[0075] S3. Add 100 mg of COF-V and 1000 mg of monomer C into an eggplant-shaped bottle containing N,N-dimethylformamide and disperse them by ultrasonication for 2 min. Then add 20 mg of initiator azobisisobutyronitrile and heat to 65 °C in a nitrogen environment for 18 h.

[0076] S4, the brown-yellow precipitate was collected by centrifugation at 9500 rpm for 5 min, and washed three times with pure water and ethanol respectively, and then dried in a vacuum drying oven for 24 h to obtain anionic polymer grafted covalent organic framework material COF- g -PAMPS.

[0077] Example 7

[0078] like Figure 1 As shown, this embodiment also provides an anionic polymer grafted covalent organic framework material COF- g -PAMPS preparation method, the preparation process is as follows:

[0079] S1. Add 14 mg of monomer A and 11.16 mg of monomer B to a centrifuge tube. Then, add 5 mL of acetonitrile to the centrifuge tube and sonicate the mixture for 1 minute to completely dissolve the monomers. Then add 0.4 mL of 12 M acetic acid to the centrifuge tube, shake vigorously on a rotary shaker for 10 s, and let stand at room temperature for 72 h.

[0080] S2. The yellow precipitate was collected by centrifugation at 9500 rpm for 5 min, washed three times with tetrahydrofuran and methanol respectively, and dried in a vacuum drying oven for 24 h to obtain the covalent organic framework material COF-V.

[0081] S3. Add 100 mg of COF-V and 2000 mg of monomer C into an eggplant-shaped bottle containing N,N-dimethylformamide and disperse them by ultrasonication for 2 min. Then add 20 mg of initiator azobisisobutyronitrile and heat to 65 °C in a nitrogen environment for reaction for 18 h.

[0082] S4, the brown-yellow precipitate was collected by centrifugation at 9500 rpm for 5 min, and washed three times with pure water and ethanol respectively, and then dried in a vacuum drying oven for 24 h to obtain anionic polymer grafted covalent organic framework material COF- g -PAMPS.

[0083] Example 8

[0084] like Figure 1 As shown, this embodiment also provides an anionic polymer grafted covalent organic framework material COF- g -PAMPS preparation method, the preparation process is as follows:

[0085] S1. Add 14 mg of monomer A and 11.16 mg of monomer B to a centrifuge tube. Then, add 5 mL of acetonitrile to the centrifuge tube and sonicate the mixture for 1 minute to completely dissolve the monomers. Then add 0.4 mL of 12 M acetic acid to the centrifuge tube, shake vigorously on a rotary shaker for 10 s, and let stand at room temperature for 72 h.

[0086] S2. The yellow precipitate was collected by centrifugation at 9500 rpm for 5 min, washed three times with tetrahydrofuran and ethanol respectively, and dried in a vacuum drying oven for 24 h to obtain the covalent organic framework material COF-V.

[0087] S3. Add 100 mg of COF-V and 1000 mg of monomer C into an eggplant-shaped bottle filled with methanol and disperse them by ultrasonication for 2 min. Then add 20 mg of initiator azobisisobutyronitrile and heat to 65 °C in a nitrogen environment for reaction for 18 h.

[0088] S4, the brown-yellow precipitate was collected by centrifugation at 9500 rpm for 5 min, and washed three times with pure water and ethanol respectively, and then dried in a vacuum drying oven for 24 h to obtain anionic polymer grafted covalent organic framework material COF- g -PAMPS.

[0089] Example 9

[0090] like Figure 1 As shown, this embodiment also provides an anionic polymer grafted covalent organic framework material COF- g -PAMPS preparation method, the preparation process is as follows:

[0091] S1. Add 14 mg of monomer A and 11.16 mg of monomer B to a centrifuge tube. Then, add 5 mL of acetonitrile to the centrifuge tube and sonicate the mixture for 1 minute to completely dissolve the monomers. Then add 0.4 mL of 12 M acetic acid to the centrifuge tube, shake vigorously on a rotary shaker for 10 s, and let stand at room temperature for 72 h.

[0092] S2. The yellow precipitate was collected by centrifugation at 9500 rpm for 5 min, washed three times with tetrahydrofuran and ethanol respectively, and dried in a vacuum drying oven for 24 h to obtain the covalent organic framework material COF-V.

[0093] S3. Add 100 mg of COF-V and 1000 mg of monomer C into an eggplant-shaped bottle containing N,N-dimethylformamide and disperse them by ultrasonication for 2 min. Then add 30 mg of initiator azobisisobutyronitrile and heat to 65 °C in a nitrogen environment for reaction for 18 h.

[0094] S4, the brown-yellow precipitate was collected by centrifugation at 9500 rpm for 5 min, and washed three times with pure water and ethanol respectively, and then dried in a vacuum drying oven for 24 h to obtain anionic polymer grafted covalent organic framework material COF- g -PAMPS.

[0095] Example 10

[0096] like Figure 1 As shown, this embodiment also provides an anionic polymer grafted covalent organic framework material COF- g -PAMPS preparation method, the preparation process is as follows:

[0097] S1. Add 14 mg of monomer A and 11.16 mg of monomer B to a centrifuge tube. Then, add 5 mL of acetonitrile to the centrifuge tube and sonicate the mixture for 1 minute to completely dissolve the monomers. Then add 0.4 mL of 12 M acetic acid to the centrifuge tube, shake vigorously on a rotary shaker for 10 s, and let stand at room temperature for 72 h.

[0098] S2. The yellow precipitate was collected by centrifugation at 9500 rpm for 5 min, washed three times with tetrahydrofuran and ethanol respectively, and dried in a vacuum drying oven for 24 h to obtain the covalent organic framework material COF-V.

[0099] S3. Add 100 mg of COF-V and 1000 mg of monomer C into an eggplant-shaped bottle containing N,N-dimethylformamide and disperse them by ultrasonication for 2 min. Then add 20 mg of initiator dibenzoyl peroxide and heat to 105 °C in a nitrogen environment for reaction for 24 h.

[0100] S4, the brown-yellow precipitate was collected by centrifugation at 9500 rpm for 5 min, and washed three times with pure water and ethanol respectively, and then dried in a vacuum drying oven for 24 h to obtain anionic polymer grafted covalent organic framework material COF- g -PAMPS.

[0101] Embodiment 11

[0102] This embodiment provides a method of grafting the anionic polymer prepared in Example 1 onto a covalent organic framework material COF- g - Application of PAMPS in the preparation of a drug system for treating inflammatory bowel disease, in which the active pharmaceutical ingredients carried can be one or more of small molecular weight oral drugs such as metformin, sodium salicylate, 5-aminosalicylic acid and glucocorticoids that can effectively treat inflammatory bowel disease:

[0103] Specifically, the active ingredient in the drug system for treating inflammatory bowel disease in this embodiment is sodium salicylate.

[0104] Specifically, for the treatment of inflammatory bowel disease, anionic polymer grafted covalent organic framework material COF- g -The preparation process of the PAMPS drug system is as follows:

[0105] First, 10 mg of sodium salicylate was dissolved in 10 mL of water, and 10 mg of COF- g -PAMPS was stirred for 6 hours to obtain COF- g -PAMPS drug system.

[0106] Example 12

[0107] This embodiment provides a method of grafting the anionic polymer prepared in Example 1 onto a covalent organic framework material COF- g-Application of PAMPS in the preparation of a drug system for treating inflammatory bowel disease. Specifically, the active ingredient in the drug system for treating inflammatory bowel disease in this embodiment is metformin.

[0108] Specifically, for the treatment of inflammatory bowel disease, anionic polymer grafted covalent organic framework material COF- g -The preparation process of the PAMPS drug system is as follows:

[0109] First, 10 mg of metformin was dissolved in 10 mL of water, and 10 mg of COF- g -PAMPS was stirred for 6 hours to obtain COF loaded with metformin g -PAMPS drug system.

[0110] Embodiment 13

[0111] This example is used to characterize the COF-V and COF- g -Nature of PAMPS.

[0112] Specifically, Figure 2 As shown, COF-V and COF- g -Physical picture of PAMPS.

[0113] like Figure 3 COF-V prepared by the preparation method described in Example 1 and COF- g -PAMPS infrared spectrum shows that the infrared absorption peak of COF-V synthesized from monomers A and B changes after being modified by monomer C. g -PAMPS at 1035 cm -1 Obvious characteristic peaks appeared, which were attributed to the stretching vibration characteristic absorption peaks of SO in the sulfonate group, confirming the successful grafting of monomer C. At the same time, the appearance of the grafted flexible polymer chain distorted the long-range ordered structure and the π-π stacking between the layers, making COF- g -PAMPS X-ray diffraction also changes as Figure 4 shown.

[0114] The COF- g -PAMPS was immersed in gastric juice and intestinal juice for 6 hours respectively, and it was found that it could resist gastric juice and intestinal juice. Figure 5 As shown, COF- g -PAMPS (i.e., sp-COF- g-PAMPS) still maintains the same original COF- g -PAMPs consistent micromorphology, such as Figure 6 As shown, COF- g -PAMPS (i.e., sp-COF- g -PAMPS) with the original COF- g -PAMPS still maintain similar zeta potential.

[0115] Embodiment 14

[0116] This example is used to verify the metformin-loaded COF- g -COF in PAMPS Drug System g -PAMPS drug loading and release capacity of metformin.

[0117] Specifically, the drug loading capacity verification experiment is as follows:

[0118] 10 mg of metformin was dissolved in 10 mL of water to form a 1 mg / mL metformin solution, which was diluted 200 times and then placed in a UV spectrophotometer for testing. Similarly, the COF- g -PAMPS drug system was diluted 200 times and then put into UV spectrophotometer for testing.

[0119] The drug release capacity was verified by the following experiment: COF- g -PAMPS drug system was dispersed in 10 mL of water, and then the dispersion was placed in a shaker at 37°C. Part of the liquid was taken out at each time point and measured in a UV spectrophotometer to obtain the drug release profile. Figure 7 As shown. Figure 7 As shown, over time, COF- g -The concentration of metformin in the PAMPS drug system increased steadily, suggesting that COF loaded with metformin g -PAMPS drug system slowly releases metformin.

[0120] Obviously, the above embodiments of the present invention are merely examples for clearly illustrating the technical solution of the present invention, and are not intended to limit the specific implementation methods of the present invention. Any modifications, equivalent substitutions and improvements made within the spirit and principles of the claims of the present invention shall be included in the protection scope of the claims of the present invention.

Claims

1. A method for preparing anionic polymer grafted covalent organic framework material, characterized in that: The following steps are involved: S1. Disperse 1 part of 1,3,5-tris(4-aminophenyl)benzene and 1-4 parts of 2,5-divinyl-1,4-benzenedicarbaldehyde in a first organic solvent according to a molar ratio to form a first monomer solution; then add 90-500 parts of acetic acid to the first monomer solution, mix well, react at room temperature and allow to stand for precipitation; S2. collecting the precipitate obtained by the reaction in step S1, washing and drying to obtain a covalent organic framework material COF-V; S3. Take 5 parts of the COF-V and 50-100 parts of 2-acrylamido-2-methyl-1-propane sulfonic acid in a mass fraction ratio and disperse them in a second organic solvent to form a second monomer solution; add 1-1.5 parts of an initiator to the second monomer solution and react and precipitate under an inert atmosphere; S4. Collect the precipitate obtained by the reaction in step S3, wash and dry it to obtain anionic polymer grafted covalent organic framework material COF- g -PAMPS.

2. The preparation method according to claim 1, characterized in that: In the step S1, the first organic solvent is acetonitrile or methanol; the concentration of the acetic acid is 12-20 M; and the reaction and standing precipitation time is 48-72 h.

3. The preparation method according to claim 1, characterized in that In step S1, the molar volume ratio of 1,3,5-tri(4-aminophenyl)benzene to the first organic solvent is not less than 1:100 mol / L.

4. The preparation method according to claim 1, characterized in that: In the step S2, the washing process is: washing the precipitate with tetrahydrofuran, and then washing with methanol or ethanol.

5. The preparation method according to claim 1, characterized in that: In step S3, the second organic solvent is selected from N,N-dimethylformamide or methanol; The initiator is selected from azobisisobutyronitrile or dibenzoyl peroxide; The process of the reaction under an inert atmosphere is: heating the second monomer solution after adding the initiator to 65-105° C. and reacting for 18-24 hours.

6. The preparation method according to claim 1, characterized in that: In the step S4, the washing process is: washing the second precipitate with pure water, and then washing with methanol or ethanol.

7. The preparation method according to any one of claims 1 to 6, characterized in that In step S2 and step S4, the precipitate 1 and the precipitate 2 are collected by centrifugation; in the centrifugation method, the rotation speed of the centrifuge is not less than 9000 rpm, and the centrifugation time is not less than 4 min.

8. Anionic polymer grafted covalent organic framework material prepared according to the preparation method according to any one of claims 1 to 7.

9. Use of the anionic polymer grafted covalent organic framework material according to claim 8 in preparing a drug system for treating inflammatory bowel disease.

10. The use of the anionic polymer grafted covalent organic framework material according to claim 9 in preparing a drug system for treating inflammatory bowel disease, characterized in that: The active ingredients in the drug system for treating inflammatory bowel disease include one or more of metformin, sodium salicylate, 5-aminosalicylic acid and glucocorticoid.

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