Ag-MOFs loaded composite hydrogel as well as preparation method and application thereof

Abstract

The invention discloses Ag-MOFs loaded composite hydrogel as well as a preparation method and application thereof, and belongs to the technical field of medical dressings. Ag2O, 1, 4-cyclohexanedicarboxylic acid and 1, 3, 5-triazine-7-phosphoric acid adamantane are taken as raw materials and added into a methanol aqueous solution, a reaction is carried out at room temperature in a dark place, a polydentate organic ligand is connected with silver ions, and the Ag-MOFs loaded composite hydrogel is obtained. The silver-based metal organic framework material is obtained; the preparation method comprises the following steps: taking oxidized kappa-carrageenan, acrylamide and a silver-based metal organic framework material as raw materials, initiating a polymerization cross-linking reaction through a cross-linking agent, a free radical initiator and a promoting initiator to obtain the Ag-MOFs loaded composite hydrogel, silver ions in the prepared silver-based metal organic framework material are released more slowly, the antibacterial property of the hydrogel is more lasting, and the antibacterial property of the hydrogel is more stable. The toxicity to cells is low; the antibacterial ability and the mechanical property of the composite hydrogel are improved, the water solubility is reduced, and the defect that part of medical dressings are insufficient in antibacterial ability is effectively overcome.

Description

Technical Field

[0001] The invention relates to the technical field of laser alloys, and in particular to an Ag-MOFs-loaded composite hydrogel and a preparation method and application thereof. Background Art

[0002] General medical dressings do not have antibacterial properties, including hydrogel medical dressings. They cannot effectively solve the problem of bacterial infection during use. When the wound is infected with bacteria, it often prolongs the wound healing time. In severe cases, it may also cause complications such as fever and inflammation.

[0003] As a kind of inorganic bactericide, silver ion has the advantages of high efficiency, non-toxicity and good stability. Among the inorganic metal ions, Ag + >Hg 2+ >Cu 2+ >Cd 2+ >Cr 3+ >Ni 2+ >Pd 2+ >Co 4+ >Zn 2+ >Fe 3+ Silver ions have the best bactericidal effect. In addition, silver ions are easily metabolized by the human body, so they are an ideal antibacterial agent. However, if silver ions are directly embedded in hydrogels, they will be easily lost, which will require a large amount of silver ions to be loaded into hydrogel dressings. However, the price of metallic silver itself is relatively high, and the cost will become a disadvantageous factor for its use as an antibacterial agent in hydrogel dressings. Therefore, it is crucial to reduce the amount of silver ions without reducing the bactericidal rate. Summary of the invention

[0004] In view of the above problems, the present invention provides an Ag-MOFs loaded composite hydrogel and a preparation method and application thereof, which effectively solves the technical problem that the direct use of metallic silver to load the hydrogel leads to the rapid loss of silver ions, thereby affecting the antibacterial property of the gel. The present invention uses organic matter as a ligand, loads silver ions into an organic ligand to prepare a silver-based metal organic skeleton, and the silver-based metal organic skeleton is connected to the silver ions through a multi-dentate organic ligand to form a porous material, so that the silver ions are released more slowly, the antibacterial property is more durable, and the cytotoxicity is low. Loading the silver-based metal organic skeleton material into the hydrogel effectively solves the disadvantage of insufficient antibacterial ability of some medical dressings.

[0005] The first object of the present invention is to provide a method for preparing an Ag-MOFs-loaded composite hydrogel, comprising the following steps: Under stirring, Ag2O, 1,4-cyclohexanedicarboxylic acid and 1,3,5-triaza-7-adamantane phosphate are added to a methanol aqueous solution, and reacted at room temperature in the dark, 1,4-cyclohexanedicarboxylic acid and 1,3,5-triaza-7-adamantane phosphate are used as ligands, silver ions are loaded into the ligands, and a silver-based metal organic framework material is obtained; the 1,4-cyclohexanedicarboxylic acid is recorded as CHDA, and the 1,3,5-triaza-7-adamantane phosphate is recorded as PTA.

[0006] At 50°C to 65°C, acrylamide monomer is initiated to undergo a polymerization crosslinking reaction under the action of a crosslinking agent, a free radical initiator and a catalytic initiator to obtain polyacrylamide gel. The polyacrylamide gel and oxidized κ-carrageenan are used as carriers, and the silver-based metal organic framework material is loaded into the structure of the carrier to obtain an Ag-MOFs-loaded composite hydrogel.

[0007] As a preferred embodiment, the mass ratio of the silver-based metal organic framework material, oxidized κ-carrageenan and acrylamide is 1:37.5-187.5:50-250. The concentration of the cross-linking agent is 0.01 g / mL, the concentration of the free radical initiator is 0.25 mol / L, and the amount ratio of acrylamide, cross-linking agent, free radical initiator and accelerator is 3 g:900 µL:320 µL:20 µL.

[0008] As a preferred embodiment, potassium chloride is added while adding the crosslinking agent, the free radical initiator and the accelerator, and the mass ratio of the silver-based metal organic framework material to potassium chloride is 1:1-5.

[0009] As a preferred embodiment, the mass ratio of Ag2O, 1,4-cyclohexanedicarboxylic acid and 1,3,5-triaza-7-phosphoric acid adamantane is 1:1.4-2.9:1.0-2.1.

[0010] As a preferred embodiment, the preparation method of the Ag-MOFs loaded composite hydrogel is specifically as follows: heating water to 50°C to 65°C, adding oxidized κ-carrageenan and acrylamide under stirring, dissolving, adding the silver-based metal organic framework material, stirring, sequentially adding a crosslinking agent, a free radical initiator and a catalytic initiator, polymerizing and crosslinking, and obtaining the Ag-MOFs loaded composite hydrogel As a preferred embodiment, the reaction time at room temperature and in the dark is 15 min to 50 min.

[0011] As a preferred embodiment, after the reaction is completed at room temperature and in the dark, a mixed solution is obtained, the pH value of the mixed solution is adjusted to 9, filtered to obtain a filtrate, and crystallized to obtain a silver-based metal organic framework material. As a preferred embodiment, the method for preparing oxidized κ-carrageenan comprises the following steps: Heat water to 70°C to 90°C, add κ-carrageenan in a stirring state, dissolve it, cool it to room temperature, add 2,2,6,6-tetramethylpiperidin-1-oxyl free radical and sodium bromide, add an equal amount of NaClO solution in 5 times within 20 minutes, adjust the pH to 10-11 after the first addition of NaClO solution, continue the reaction after the NaClO solution is completely added, add anhydrous ethanol, let it stand, neutralize the reaction solution, concentrate it at 50°C to 65°C, dialyze, and freeze-dry to obtain oxidized κ-carrageenan; wherein the concentration of the NaClO solution is 1.53 mol / L, and the amount ratio of the κ-carrageenan, 2,2,6,6-tetramethylpiperidin-1-oxyl free radical, sodium bromide and NaClO solution is 7.9 g:120 mg:1.5 g:32.5 mL.

[0012] As a preferred embodiment, the crosslinking agent is N,N-methylenebisacrylamide, the accelerator is N,N,N',N'-tetramethylethylenediamine, and the free radical initiator is ammonium persulfate.

[0013] The second object of the present invention is to provide an Ag-MOFs-loaded composite hydrogel prepared by the preparation method of the above-mentioned Ag-MOFs-loaded composite hydrogel.

[0014] The third object of the present invention is to provide an application of the above-mentioned Ag-MOFs loaded composite hydrogel in the preparation of antibacterial dressings.

[0015] Compared with the prior art, the present invention has the following beneficial effects: The invention uses Ag2O, 1,4-cyclohexanedicarboxylic acid and 1,3,5-triaza-7-phosphoric acid adamantane as raw materials, adds them into methanol aqueous solution, reacts at room temperature in the dark, uses organic matter as ligand, loads silver ions into organic ligands, obtains silver-based metal organic framework materials, recorded as Ag-MOFs, because the silver-based metal organic framework materials are connected with silver ions through multi-dentate organic ligands to form porous materials, so that the silver ions are released more slowly, which will make the antibacterial property of the hydrogel more durable and low in cell toxicity; then, oxidized kappa-carrageenan, acrylamide and silver-based metal organic framework materials are used as raw materials, and a crosslinking agent, a free radical initiator and a promoter are added to initiate a polymerization crosslinking reaction, in which acrylamide is used as a monomer, and polymerization and crosslinking are carried out under the action of the crosslinking agent, the free radical initiator and the promoter to obtain polyacrylamide gel, and the silver-based metal organic framework materials are loaded into the oxidized kappa-carrageenan and polyacrylamide gel structures to obtain Ag-MOFs loaded composite hydrogel, recorded as Ag-MOFs / OKC / PAM hydrogel. The present invention loads Ag-MOFs into OKC / PAM hydrogel, which not only improves the antibacterial ability of the composite hydrogel, but also improves the mechanical properties of the composite hydrogel and reduces the water solubility, effectively solving the disadvantage of insufficient antibacterial ability of some medical dressings. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] Figure 1 This is the X-ray diffraction pattern of Ag-MOFs prepared in Examples 1 to 4 of the present invention.

[0017] Figure 2 This is a comparison chart of infrared spectra of 1,4-cyclohexanedicarboxylic acid, 1,3,5-triaza-7-phosphoric acid adamantane and the prepared Ag-MOFs used in Examples 1 to 4 of the present invention.

[0018] Figure 3 It is a comparison chart of the water content of the composite hydrogel of comparative example 1 of the present invention and the Ag-MOFs-loaded composite hydrogels of Examples 1 to 4, wherein A1 is comparative example 1, B1 is example 1, C1 is example 2, and D1 is example 3.

[0019] Figure 4 It is a comparison chart of the water solubility of the composite hydrogel of comparative example 1 of the present invention and the Ag-MOFs-loaded composite hydrogels of Examples 1 to 4, wherein A1 is comparative example 1, B1 is example 1, C1 is example 2, and D1 is example 3.

[0020] Figure 5 It is a comparison chart of the swelling rates of the composite hydrogel of comparative example 1 of the present invention and the Ag-MOFs-loaded composite hydrogels of examples 1 to 4, wherein A1 is comparative example 1, B1 is example 1, C1 is example 2, and D1 is example 3.

[0021] Figure 6 It is a comparison chart of the tensile strength of the composite hydrogel of comparative example 1 of the present invention and the Ag-MOFs-loaded composite hydrogels of Examples 1 to 4, wherein A1 is comparative example 1, B1 is example 1, C1 is example 2, and D1 is example 3.

[0022] Figure 7 It is a comparison chart of the elongation at break of the composite hydrogel of comparative example 1 of the present invention and the Ag-MOFs-loaded composite hydrogels of Examples 1 to 4, wherein A1 is comparative example 1, B1 is example 1, C1 is example 2, and D1 is example 3.

[0023] Figure 8 The scanning electron microscope images are of the composite hydrogel of comparative example 1 and the Ag-MOFs loaded composite hydrogels of examples 1 to 4 of the present invention, wherein A1 is comparative example 1, B1 is example 1, C1 is example 2, and D1 is example 3.

[0024] Fig. 9 This is a graph of the diameter of the inhibition zone of Escherichia coli for the composite hydrogel of Comparative Example 1 of the present invention and the Ag-MOFs-loaded composite hydrogels of Examples 1 to 4, wherein A1 is Comparative Example 1, B1 is Example 1, C1 is Example 2, and D1 is Example 3.

[0025] Fig.10 It is a columnar comparison chart of the diameter of the inhibition zone of Escherichia coli of the composite hydrogel of comparative example 1 of the present invention and the Ag-MOFs-loaded composite hydrogels of Examples 1 to 4, wherein A1 is comparative example 1, B1 is example 1, C1 is example 2, and D1 is example 3.

[0026] Fig.11 This is a graph of the diameter of the inhibition zone of the composite hydrogel of comparative example 1 of the present invention and the Ag-MOFs-loaded composite hydrogels of Examples 1 to 4 against Staphylococcus aureus, wherein A1 is comparative example 1, B1 is example 1, C1 is example 2, and D1 is example 3.

[0027] Fig.12 It is a columnar comparison chart of the diameter of the inhibition zone of Staphylococcus aureus of the composite hydrogel of comparative example 1 of the present invention and the Ag-MOFs-loaded composite hydrogels of Examples 1 to 4, wherein A1 is comparative example 1, B1 is example 1, C1 is example 2, and D1 is example 3.

[0028] Fig.13 It is a comparison chart of the survival rates of L929 cells in the composite hydrogel of Comparative Example 1 of the present invention and the Ag-MOFs-loaded composite hydrogels of Examples 1 to 4, wherein A1 is Comparative Example 1, B1 is Example 1, C1 is Example 2, and D1 is Example 3. DETAILED DESCRIPTION

[0029] In order to enable those skilled in the art to better understand the technical solution of the present invention and implement it, the present invention is further described below in conjunction with specific examples, but the examples are not intended to limit the present invention. The following test methods and detection methods, unless otherwise specified, are conventional methods; the reagents and raw materials, unless otherwise specified, are commercially available.

[0030] The technical solution of the present invention is described in detail below.

[0031] The present invention first provides a method for preparing an Ag-MOFs-loaded composite hydrogel, comprising the following steps: Under stirring, Ag2O, 1,4-cyclohexanedicarboxylic acid and 1,3,5-triaza-7-phosphoric acid adamantane are added to a methanol aqueous solution, reacted at room temperature in the dark, silver ions are loaded into the organic ligand with organic matter as ligand, the pH value is adjusted to 9, filtered to obtain a filtrate, crystallized, and a silver-based metal organic framework material is obtained.

[0032] The water is heated to 50° C. to 65° C., oxidized κ-carrageenan and acrylamide are added and dissolved under stirring, the silver-based metal organic framework material is added and stirred, a cross-linking agent, a free radical initiator and a promoter are added in sequence, and the reaction is carried out at 50° C. to 65° C., acrylamide is used as a monomer, and polymerization and cross-linking are carried out under the action of the cross-linking agent, the free radical initiator and the promoter to obtain polyacrylamide gel, and the silver-based metal organic framework material is loaded into the oxidized κ-carrageenan and the polyacrylamide gel structure to obtain the Ag-MOFs loaded composite hydrogel.

[0033] Note that during the dissolution and reaction process, the bottle mouth should be sealed with plastic wrap to reduce water evaporation.

[0034] In the above technical solution, since the silver-based metal-organic framework material is connected to silver ions through multi-dentate organic ligands to form a porous material, the release of silver ions is slower, which will make the antibacterial property of the hydrogel more durable and have low cytotoxicity; the present invention loads Ag-MOFs into OKC / PAM hydrogel, which not only improves the antibacterial ability of the composite hydrogel, but also improves the mechanical properties of the composite hydrogel and reduces the water solubility, effectively solving the disadvantage of insufficient antibacterial ability of some medical dressings.

[0035] In order to achieve the best sterilization effect without causing waste of raw materials, the mass ratio of Ag2O, 1,4-cyclohexanedicarboxylic acid and 1,3,5-triaza-7-phosphoric acid adamantane is 1:1.43-2.88:1.04-2.10. As for the amount of Ag2O, if the amount of Ag2O added is small, it cannot play a sterilization role and the terminal yield is low; if the amount of Ag2O added is large, it will cause excess, and Ag2O is difficult to remove in the reaction system, but becomes an impurity.

[0036] In order to obtain the target product with a better yield, the reaction time at room temperature and in the dark is 15 minutes to 50 minutes, and the yield is highest at 30 minutes. If the reaction time is less than 15 minutes, the reaction is incomplete and the yield is low. If the reaction time exceeds 50 minutes, the stirring reaction time is too long, and the methanol in the reaction system evaporates excessively, resulting in solid precipitation, and the product content in the filtrate obtained by subsequent filtration is reduced.

[0037] It should be noted that the preparation method of the oxidized κ-carrageenan comprises the following steps: Measure 600 mL of deionized water in a 2L beaker, place the beaker in a magnetic stirring water bath and heat it to 90 °C, slowly add 7.9 g of κ-carrageenan under stirring conditions, stir until the carrageenan is completely dissolved, take out the beaker, cool it to room temperature, add 120 mg of 2,2,6,6-tetramethylpiperidin-1-oxyl free radical, recorded as TEMPO and 1.5 g of NaBr, stir evenly, add 32.5 mL of 1.53 mol / L NaClO solution in 5 times within 20 minutes, add 6.5 mL every 5 minutes, after the first addition of NaClO solution, adjust the pH value to 10.8 with 1 mol / L NaOH solution, and maintain the pH of the reaction solution at 10.5-10.8 during the subsequent reaction process, after the NaClO solution is completely added, continue to stir the reaction for 100 minutes, finally add 250 mL of anhydrous ethanol to terminate the reaction, stir evenly and let stand for 1 hour, use 1 mol / L The mixture was neutralized with HCl and then transferred to a rotary evaporator and concentrated to about 300 mL at 60 °C. The reaction solution was then placed in a dialysis bag and placed in deionized water. Dialysis was performed at 4 °C for 3 days, with the water changed 4 times a day. After the dialysis was completed, it was freeze-dried in a vacuum freeze dryer to obtain oxidized κ-carrageenan, recorded as OKC, and placed in a -20 °C refrigerator for standby use.

[0038] In order to ensure the mechanical properties of the composite hydrogel, the concentration of the crosslinking agent used in the present invention is 0.01g / mL, the concentration of the free radical initiator is 0.25moL / L, and the dosage ratio of the oxidized κ-carrageenan, acrylamide, silver-based metal organic framework material, crosslinking agent, free radical initiator and accelerator is 2.25g:3g:12mg~60mg:900µL:320µL:20µL. For the addition amount of the silver-based metal organic framework material, if the addition amount is too low, the mechanical properties of the composite hydrogel such as water content, tensile strength and elongation at break are low; if the addition amount is too high, the gel will be excessively crosslinked, resulting in the collapse of the gel structure, and the reduction of mechanical properties such as water resistance, water absorption, swelling rate, tensile strength and elongation at break.

[0039] In order to further promote the rapid occurrence of the cross-linking reaction, potassium chloride is added while adding the cross-linking agent, the free radical initiator and the promoter. The mass ratio of the silver-based metal organic framework material to potassium chloride is 1:1-5. The addition of potassium chloride can not only accelerate the occurrence of the cross-linking reaction, but also improve the structural stability and mechanical properties of the generated hydrogel, thereby forming a strong hydrogel network, effectively preventing the loss of silver ions and causing a decrease in the antibacterial properties of the hydrogel.

[0040] In order to improve the strength of the generated composite hydrogel, the crosslinking agent is N,N-methylenebisacrylamide, the initiator is N,N,N',N'-tetramethylethylenediamine, and the free radical initiator is ammonium persulfate.

[0041] The present invention is specifically described below by means of the following examples and comparative examples.

[0042] The method for preparing oxidized κ-carrageenan used in the following embodiments of the present invention comprises the following steps: Measure 600 mL of deionized water in a 2L beaker, place the beaker in a magnetic stirring water bath and heat it to 90 °C, slowly add 7.9 g of κ-carrageenan under stirring conditions, stir until the carrageenan is completely dissolved, take out the beaker, cool it to room temperature, add 120 mg of 2,2,6,6-tetramethylpiperidin-1-oxyl free radical, recorded as TEMPO and 1.5 g of NaBr, stir evenly, add 32.5 mL of 1.53 mol / L NaClO solution in 5 times within 20 minutes, add 6.5 mL every 5 minutes, after the first addition of NaClO solution, adjust the pH value to 10.8 with 1 mol / L NaOH solution, and maintain the pH of the reaction solution at 10.5-10.8 during the subsequent reaction process, after the NaClO solution is completely added, continue to stir the reaction for 100 minutes, finally add 250 mL of anhydrous ethanol to terminate the reaction, stir evenly and let stand for 1 hour, use 1 mol / L The mixture was neutralized with HCl and then transferred to a rotary evaporator and concentrated to about 300 mL at 60 °C. The reaction solution was then placed in a dialysis bag and placed in deionized water. Dialysis was performed at 4 °C for 3 days, with the water changed 4 times a day. After the dialysis was completed, it was freeze-dried in a vacuum freeze dryer to obtain oxidized κ-carrageenan, recorded as OKC, and placed in a -20 °C refrigerator for standby use.

[0043] Example 1 A method for preparing an Ag-MOFs-loaded composite hydrogel comprises the following steps: 28 mL of methanol and 12 mL of deionized water were measured in a 100 mL beaker, and the beaker was placed on a magnetic stirrer. Under stirring, 92 mg of Ag2O, 172.4 mg of 1,4-cyclohexanedicarboxylic acid and 125.6 mg of 1,3,5-triaza-7-phosphoric acid adamantane were added. The mixture was reacted at room temperature in the dark for 30 min to obtain a white turbid liquid. 1.6 mL of 1 mol / L ammonia water was added dropwise to adjust the pH value to 9 to obtain a mixed solution. The mixed solution was filtered through filter paper, and the filtrate was collected and poured into a culture dish. It was naturally crystallized in a fume hood with good ventilation conditions for 2 days to obtain a light yellow solid powder, which was placed in a 4 °C refrigerator to obtain a silver-based metal organic framework material, recorded as Ag-MOFs.

[0044] Measure 25 mL of deionized water in a 100 mL beaker, place the beaker on a magnetic stirrer, heat to 60 °C, add 2.25 g of oxidized κ-carrageenan, recorded as OKC, stir until completely dissolved, add 3 g of acrylamide, after complete dissolution, add 12 mg of Ag-MOFs, continue stirring for 20 min, add 900 μL of 0.01 g / mL N,N-methylenebisacrylamide solution, 20 μL of N,N,N',N'-tetramethylethylenediamine, 320 μL of 0.25 mol / L ammonium persulfate and 60 mgKCl in sequence, continue stirring for 20 min, pour the reaction solution into a 90 mm×90 mm×1.5 mm acrylic mold, seal it, put it in a 60 °C constant temperature box for reaction for 4 h, and then take it out to obtain Ag-MOFs loaded composite hydrogel, recorded as Ag-MOFs / OKC / PAM hydrogel.

[0045] Example 2 A method for preparing an Ag-MOFs-loaded composite hydrogel comprises the following steps: 28 mL of methanol and 12 mL of deionized water were measured in a 100 mL beaker, and the beaker was placed on a magnetic stirrer. Under stirring, 92 mg of Ag2O, 172.4 mg of 1,4-cyclohexanedicarboxylic acid and 125.6 mg of 1,3,5-triaza-7-phosphoric acid adamantane were added. The mixture was reacted at room temperature in the dark for 30 min to obtain a white turbid liquid. 1.6 mL of 1 mol / L ammonia water was added dropwise to adjust the pH value to 9 to obtain a mixed solution. The mixed solution was filtered through filter paper, and the filtrate was collected and poured into a culture dish. It was naturally crystallized in a fume hood with good ventilation conditions for 2 days to obtain a light yellow solid powder, which was placed in a 4 °C refrigerator to obtain a silver-based metal organic framework material, recorded as Ag-MOFs.

[0046] Measure 25 mL of deionized water in a 100 mL beaker, place the beaker on a magnetic stirrer, heat to 60 °C, add 2.25 g of oxidized κ-carrageenan, recorded as OKC, stir until completely dissolved, add 3 g of acrylamide, after complete dissolution, add 24 mg of Ag-MOFs, continue stirring for 20 min, add 900 μL of 0.01 g / mL N,N-methylenebisacrylamide solution, 20 μL of N,N,N',N'-tetramethylethylenediamine, 320 μL of 0.25 mol / L ammonium persulfate and 60 mgKCl in sequence, continue stirring for 20 min, pour the reaction solution into a 90 mm×90 mm×1.5 mm acrylic mold, seal it, put it in a 60 °C constant temperature box for reaction for 4 h, and then take it out to obtain Ag-MOFs loaded composite hydrogel, recorded as Ag-MOFs / OKC / PAM hydrogel.

[0047] Example 3 A method for preparing an Ag-MOFs-loaded composite hydrogel comprises the following steps: 28 mL of methanol and 12 mL of deionized water were measured in a 100 mL beaker, and the beaker was placed on a magnetic stirrer. Under stirring, 92 mg of Ag2O, 172.4 mg of 1,4-cyclohexanedicarboxylic acid and 125.6 mg of 1,3,5-triaza-7-phosphoric acid adamantane were added. The mixture was reacted at room temperature in the dark for 30 min to obtain a white turbid liquid. 1.6 mL of 1 mol / L ammonia water was added dropwise to adjust the pH value to 9 to obtain a mixed solution. The mixed solution was filtered through filter paper, and the filtrate was collected and poured into a culture dish. It was naturally crystallized in a fume hood with good ventilation conditions for 2 days to obtain a light yellow solid powder, which was placed in a 4°C refrigerator to obtain a silver-based metal organic framework material, recorded as Ag-MOFs.

[0048] Measure 25 mL of deionized water in a 100 mL beaker, place the beaker on a magnetic stirrer, heat to 60 °C, add 2.25 g of oxidized κ-carrageenan, recorded as OKC, stir until completely dissolved, add 3 g of acrylamide, after complete dissolution, add 36 mg of Ag-MOFs, continue stirring for 20 min, add 900 μL of 0.01 g / mL N,N-methylenebisacrylamide solution, 20 μL of N,N,N',N'-tetramethylethylenediamine, 320 μL of 0.25 mol / L ammonium persulfate and 60 mgKCl in sequence, continue stirring for 20 min, pour the reaction solution into a 90 mm×90 mm×1.5 mm acrylic mold, seal it, put it in a 60 °C constant temperature box for reaction for 4 h, and then take it out to obtain Ag-MOFs loaded composite hydrogel, recorded as Ag-MOFs / OKC / PAM hydrogel.

[0049] Example 4 A method for preparing an Ag-MOFs-loaded composite hydrogel comprises the following steps: 28 mL of methanol and 12 mL of deionized water were measured in a 100 mL beaker, and the beaker was placed on a magnetic stirrer. Under stirring, 92 mg of Ag2O, 172.4 mg of 1,4-cyclohexanedicarboxylic acid and 125.6 mg of 1,3,5-triaza-7-phosphoric acid adamantane were added. The mixture was reacted at room temperature in the dark for 30 min to obtain a white turbid liquid. 1.6 mL of 1 mol / L ammonia water was added dropwise to adjust the pH value to 9 to obtain a mixed solution. The mixed solution was filtered through filter paper, and the filtrate was collected and poured into a culture dish. It was naturally crystallized in a fume hood with good ventilation conditions for 2 days to obtain a light yellow solid powder, which was placed in a 4°C refrigerator to obtain a silver-based metal organic framework material, recorded as Ag-MOFs.

[0050] Measure 25 mL of deionized water in a 100 mL beaker, place the beaker on a magnetic stirrer, heat to 60 °C, add 2.25 g of oxidized κ-carrageenan, recorded as OKC, stir until completely dissolved, add 3 g of acrylamide, after complete dissolution, add 60 mg of Ag-MOFs, continue stirring for 20 min, add 900 μL of 0.01 g / mL N,N-methylenebisacrylamide solution, 20 μL of N,N,N',N'-tetramethylethylenediamine, 320 μL of 0.25 mol / L ammonium persulfate and 60 mgKCl in sequence, continue stirring for 20 min, pour the reaction solution into a 90 mm×90 mm×1.5 mm acrylic mold, seal it, put it in a 60 °C constant temperature box for reaction for 4 h, and then take it out to obtain Ag-MOFs loaded composite hydrogel, recorded as Ag-MOFs / OKC / PAM hydrogel.

[0051] In order to further illustrate the effect of the present invention, the present invention also sets a comparative example, as follows: Comparative Example 1 Compared with Example 1, the difference is that no silver-based metal organic framework material is added to the composite hydrogel.

[0052] A method for preparing an Ag-MOFs-loaded composite hydrogel comprises the following steps: 28 mL of methanol and 12 mL of deionized water were measured in a 100 mL beaker, and the beaker was placed on a magnetic stirrer. Under stirring, 92 mg of Ag2O, 172.4 mg of 1,4-cyclohexanedicarboxylic acid and 125.6 mg of 1,3,5-triaza-7-phosphoric acid adamantane were added. The mixture was reacted at room temperature in the dark for 30 min to obtain a white turbid liquid. 1.6 mL of 1 mol / L ammonia water was added dropwise to adjust the pH value to 9 to obtain a mixed solution. The mixed solution was filtered through filter paper, and the filtrate was collected and poured into a culture dish. It was naturally crystallized in a fume hood with good ventilation conditions for 2 days to obtain a light yellow solid powder, which was placed in a 4 °C refrigerator to obtain a silver-based metal organic framework material, recorded as Ag-MOFs.

[0053] Measure 25 mL of deionized water in a 100 mL beaker, place the beaker on a magnetic stirrer, heat to 60 °C, add 2.25 g of oxidized κ-carrageenan, recorded as OKC, stir until completely dissolved, add 3 g of acrylamide, after complete dissolution, add 0 mg of Ag-MOFs, continue stirring for 20 min, add 900 μL of 0.01 g / mL N,N-methylenebisacrylamide solution, 20 μL of N,N,N',N'-tetramethylethylenediamine, 320 μL of 0.25 mol / L ammonium persulfate and 60 mgKCl in sequence, continue stirring for 20 min, pour the reaction solution into a 90 mm×90 mm×1.5 mm acrylic mold, seal it, put it in a 60 °C constant temperature box for reaction for 4 h, and then take it out to obtain a composite hydrogel.

[0054] Various properties of the Ag-MOFs loaded composite hydrogels prepared in Examples 1 to 4 and the composite hydrogel prepared in Comparative Example 1 were tested, and the results are as follows.

[0055] 1. Ag-MOFs X-ray diffraction X-ray diffraction patterns of Ag-MOFs are shown in Figure 1 As shown, in the XRD spectrum of Ag-MOFs, 2θ of 6.3, 10.0, 11.7, 12.5, 13.1, 14.7, 15.5, 16.5, 19.6, 25.3, 26.4, 27.8, and 32.3 are the characteristic peaks of Ag-MOFs.

[0056] 2. Fourier transform infrared spectroscopy analysis of Ag-MOFs The infrared spectrum analysis results of CHDA, PTA and Ag-MOFs are as follows Figure 2 As shown. Figure 2 It can be seen that the characteristic peak of CHDA near 2956 cm-1 is attributed to the asymmetric and symmetric stretching vibration peaks of -CH2, and the characteristic peak at 1688 cm -1 The absorption peak at 1699 cm is the carbonyl stretching vibration peak of 1,4-cyclohexanedicarboxylic acid. -1 1640 cm -1 A new absorption peak appeared, which can be attributed to the symmetrical stretching vibration peak of carboxyl group, indicating that Ag-MOFs contain carboxyl groups. In addition, at 1369 cm -1 and 1445 cm -1 The characteristic absorption peaks of CHDA and TPA appeared at , respectively, indicating that Ag-MOFs were synthesized.

[0057] 3. Moisture content and water solubility of Ag-MOFs / OKC / PAM A moist environment can promote wound healing and reduce scars. Therefore, as a hydrogel dressing, its water content and water solubility are important indicators. Figure 3 It can be seen that the water content of hydrogels with different Ag-MOFs contents is different. The water contents of Comparative Example 1, Example 1 to Example 4 are 76.36%, 78.62%, 80.77%, 82.13%, and 82.7%, respectively; this shows that with the increase of Ag-MOFs, the water content of the hydrogel will also increase accordingly. When the Ag-MOFs content in the hydrogel increases to 36 mg (D1), the increase in water content begins to slow down and reaches the highest in E1. The increase in water content is due to the gradual increase of Ag-MOFs. The silver ions in the system cause the components in the hydrogel to be over-crosslinked, resulting in the collapse of some three-dimensional pore structures, providing more space for water molecules, and increasing the water content of the hydrogel sample. The water content of Ag-MOFs / OKC / PAM hydrogels is above 80%, which is higher than the normal skin water content of 69.59%, which meets the moist healing environment of the wound.

[0058] The water resistance of hydrogel can be evaluated by water solubility. The lower the water solubility, the better the water resistance. Figure 4 It can be seen that when there is no Ag-MOFs or the Ag-MOFs content is low, the water solubility of the hydrogel is low and there is no obvious change. As the Ag-MOFs content increases, the water solubility of the hydrogel gradually increases. This is because the hydrogel with a high Ag-MOFs content is over-crosslinked, resulting in a more chaotic structure, destroying the original relatively regular structure, and the intermolecular connection is not tight enough, destroying some three-dimensional pore structures. These collapsed structures are unstable in water and easily soluble in water. As the silver ion content increases, the amount of silver ions released in water is also more. Therefore, as the silver ion content increases, the water solubility shows an increasing trend.

[0059] 4. Ag-MOFs / OKC / PAM swelling rate When the skin is damaged and a wound occurs, there is often wound exudate. If it is not well absorbed, it will have an adverse effect on wound healing. Therefore, as a medical skin dressing, it is very necessary to have good swelling properties. Figure 5It can be seen that the swelling rate of the five hydrogels gradually increased over time, and the swelling rate change rate gradually slowed down over time. Among them, the B1, C1, D1 and E1 hydrogels tended to equilibrium at 18h, and the A1 hydrogel tended to equilibrium at 34h. At 50h, the swelling rate of the hydrogels was A1>B1>E1>D1>C1, with values ​​of 808%, 651%, 479%, 481%, and 460%, respectively. The swelling rate of the hydrogel with Ag-MOFs added was lower than that of the hydrogel without Ag-MOFs added, but the swelling rates of C1, D1 and E1 hydrogels were similar. This is because the increase in the silver ion content in the Ag-MOFs hydrogel leads to high-density cross-linking, which limits the water absorption and swelling of the hydrogel.

[0060] 5. Mechanical properties of Ag-MOFs / OKC / PAM As a medical dressing, its stress state under complex conditions needs to be considered. In order to study the mechanical properties of the hydrogel, the tensile strength and elongation at break of the Ag-MOFs / OKC / PAM hydrogel were tested. Figure 6 and Figure 7 It can be seen that the tensile strength and elongation at break of the composite hydrogel of Comparative Example 1 are 0.223 MPa and 421%, respectively, while the tensile strength and elongation at break of the Ag-MOFs-loaded composite hydrogel of Example 1 are 0.249 MPa and 440%, respectively. Therefore, the tensile strength and elongation at break of the hydrogel A1 without adding Ag-MOFs carrageenan are lower than those of the Ag-MOFs-loaded composite hydrogel. With the increase of the Ag-MOFs content, the tensile strength and elongation at break of the hydrogel both show a trend of first increasing and then decreasing (P<0.05). When the Ag-MOFs content is 12 mg, the tensile strength of the hydrogel is increased by 0.021 MPa, and the elongation at break is increased by 20.47%, respectively. This is because a small amount of silver ions enhances the formation of hydrogen bonds and electrostatic effects of other components in the hydrogel, strengthens the interaction force between the components of the hydrogel, thereby making the components of the hydrogel more closely connected, which is manifested as an increase in the tensile strength of the hydrogel and an increase in the elongation at break. When the Ag-MOFs content continued to increase, the silver ion content in the hydrogel was higher, and the tensile strength and elongation at break of the hydrogel gradually decreased. This may be because the silver ions caused the hydrogel to cross-link excessively, reducing the free chains of the hydrogel molecular chains. In addition, the carrageenan polymer itself has a certain brittleness, which affects the tensile strength of the hydrogel. Therefore, with the addition of Ag-MOFs, the elongation at break of the hydrogel decreased.

[0061] 6. Scanning electron microscopy In order to study whether the introduction of Ag-MOFs would affect the microstructure of the hydrogel, the Ag-MOFs / OKC / PAM hydrogel was freeze-dried and then tested by scanning electron microscopy. Figure 8 It can be seen that the pore structure of the Ag-MOFs-loaded composite hydrogel in Example 1 is relatively intact; Examples 2 to 4 have more wrinkles than Comparative Example 1, and the wrinkles gradually increase with the increase of the Ag-MOFs content, and the pore size is significantly larger than that of Comparative Example 1. This is because the silver ions in Ag-MOFs have an effect on the hydrogel structure. Due to the addition of silver ions, the reaction is uneven when the gel is formed. When the Ag-MOFs content is high, more silver ions are released and react with the carboxyl groups of the hydrogel molecules, causing some of the pores in the hydrogel to shrink. Overall, these four hydrogels all contain a large number of three-dimensional pore structures, which play an important role in the process of new tissue formation in the wound. Hydrogels with a large number of pores and good three-dimensional structures help absorb wound exudate and promote new tissue formation, which helps wound healing.

[0062] 7. Antibacterial performance analysis Antibacterial ability is an important evaluation index of medical dressings. Medical dressings with better antibacterial properties have a wider range of uses. In order to detect the antibacterial properties of Ag-MOFs / OKC / PAM hydrogels, this study selected Escherichia coli, E. coli and Staphylococcus aureus, S aureus, and used the inhibition zone method to conduct antibacterial tests on different types of Ag-MOFs / OKC / PAM hydrogels. The antibacterial effect can be judged according to the size of the inhibition zone. The larger the inhibition zone, the stronger the antibacterial effect. The antibacterial effect of each hydrogel is as follows. Figure 9~Figure 12 ,Depend on Fig. 9 and Fig.11 It can be seen that the sizes of the inhibition zones of hydrogel samples with different formulations are significantly different, and the antibacterial ability gradually increases with the increase of Ag-MOFs content. Fig. 9 It can be seen that the antibacterial ability of Ag-MOFs / OKC / PAM hydrogel on E. coli is that comparative example 1 has no inhibitory effect, the antibacterial circle of example 1 is 26.8 mm, the antibacterial circle of example 2 is 29.8 mm, the antibacterial circle of example 3 is 31.7 mm, and the antibacterial circle of example 4 is 33.0 mm; Fig.11 It can be seen that the antibacterial ability of Ag-MOFs / OKC / PAM hydrogel on Saureus is no inhibitory effect in comparative example 1, the inhibition zone of Example 1 is 14.5 mm, the inhibition zone of Example 2 is 15.8 mm, the inhibition zone of Example 3 is 17.2 mm, and the inhibition zone of Example 4 is 20.2 mm. This shows that the hydrogel without the addition of Ag-MOFs material has no antibacterial activity against E. coli and Saureus, while the Ag-MOFs / OKC / PAM hydrogel of Examples 1 to 4 of the present invention has strong antibacterial activity against E. coli and Saureus, as shown in FIG. Fig.10 and Fig.12 As shown in the figure, with the increase of Ag-MOFs content, the antibacterial ability gradually increases, and the antibacterial ability is strongest when the Ag-MOFs content is 60 mg. This is because the Ag-MOFs in the Ag-MOFs / OKC / PAM hydrogel can release silver ions, which have broad-spectrum antibacterial properties and can kill bacteria. The higher the silver content, the stronger the bactericidal ability. At the same time, the antibacterial activity of the hydrogel against Escherichia coli is stronger than that against Staphylococcus aureus, because silver ions are more effective in killing negative bacteria than positive bacteria, and the inhibition zone of Escherichia coli is larger than that of Staphylococcus aureus.

[0063] 8. Cytocompatibility Good biocompatibility of medical dressings is crucial for wounds. Generally, silver ion bactericides will cause certain damage to cells while killing bacteria. At the same time, the hydrogel medical dressing material itself may also have certain toxicity. Therefore, it is very important to evaluate the damage of hydrogel dressings to cells. The present invention uses L929 cells to detect the cytotoxicity of Ag-MOFs / OKC / PAM hydrogel medical dressings to determine its possibility as a medical dressing. The results are as follows Fig.13 After the cells were treated with the Ag-MOFs / OKC / PAM hydrogel sample extract for 48 hours, the cell survival rates of the Ag-MOFs-loaded composite hydrogels of Examples 1 to 4 were 99.2%, 99.5%, 97%, and 93.6%, respectively, which were all greater than 90% compared with the composite hydrogel of Comparative Example 1, indicating that the Ag-MOFs / OKC / PAM hydrogel prepared by the present invention has good cell compatibility. The cell survival rate of the cells treated with the Ag-MOFs / OKC / PAM hydrogel extracts of Examples 1 and 2 was greater than 99% after 48 hours, indicating that the cell survival rate was almost unaffected when the Ag-MOFs content was 12 mg and 24 mg, and the cell survival rate decreased significantly (P<0.05) when the Ag-MOFs content increased to 36 mg and 60 mg, respectively, to 97% and 93.6%. This is because compared with Examples 1 and 2, the silver ion concentrations of Examples 3 and 4 were higher, resulting in partial cell damage, thereby reducing the relative cell survival rate. In general, the cell survival rates of the Ag-MOFs gradient hydrogel samples of Examples 1 to 4 all exceeded 90%, indicating that the samples have good cell compatibility.

[0064] Obviously, those skilled in the art may make various changes and modifications to the present invention without departing from the spirit and scope of the present invention. Thus, if these modifications and variations of the present invention fall within the scope of the claims of the present invention and their equivalents, the present invention is also intended to include these modifications and variations.

Claims

1. A method for preparing Ag-MOFs loaded composite hydrogel, characterized in that: The following steps are involved: Under stirring, Ag2O, 1,4-cyclohexanedicarboxylic acid and 1,3,5-triaza-7-adamantane phosphate are added to a methanol aqueous solution, and reacted at room temperature in the dark, using 1,4-cyclohexanedicarboxylic acid and 1,3,5-triaza-7-adamantane phosphate as ligands, and loading silver ions into the ligands to obtain a silver-based metal organic framework material; At 50°C to 65°C, acrylamide monomer is initiated to undergo a polymerization crosslinking reaction under the action of a crosslinking agent, a free radical initiator and a catalytic initiator to obtain polyacrylamide gel. The polyacrylamide gel and oxidized κ-carrageenan are used as carriers, and the silver-based metal organic framework material is loaded into the structure of the carrier to obtain an Ag-MOFs-loaded composite hydrogel.

2. The method for preparing the Ag-MOFs loaded composite hydrogel according to claim 1, characterized in that: The mass ratio of the silver-based metal organic framework material, oxidized kappa-carrageenan and acrylamide is 1:37.5-187.5:50-250.

3. The method for preparing the Ag-MOFs loaded composite hydrogel according to claim 2, characterized in that: Potassium chloride is added while adding the crosslinking agent, the free radical initiator and the accelerator, and the mass ratio of the silver-based metal organic framework material to potassium chloride is 1:1-5.

4. The method for preparing the Ag-MOFs loaded composite hydrogel according to claim 1, characterized in that: The mass ratio of Ag2O, 1,4-cyclohexanedicarboxylic acid and 1,3,5-triaza-7-phosphoric acid adamantane is 1:1.4-2.9:1.0-2.

1.

5. The method for preparing the Ag-MOFs loaded composite hydrogel according to claim 1, characterized in that: The preparation method of the Ag-MOFs-loaded composite hydrogel is specifically as follows: heating water to 50° C. to 65° C., adding oxidized κ-carrageenan and acrylamide under stirring, dissolving them, adding the silver-based metal organic framework material, stirring, adding a cross-linking agent, a free radical initiator and a promoter in turn, polymerizing and cross-linking, and obtaining the Ag-MOFs-loaded composite hydrogel.

6. The method for preparing the Ag-MOFs loaded composite hydrogel according to claim 1, characterized in that: The reaction time at room temperature and in the dark is 15 to 50 minutes.

7. The method for preparing the Ag-MOFs loaded composite hydrogel according to claim 1, characterized in that: After the reaction is completed at room temperature in the dark, a mixed solution is obtained, the pH value of the mixed solution is adjusted to 9, filtered to obtain a filtrate, and crystallized to obtain a silver-based metal organic framework material.

8. The method for preparing the Ag-MOFs loaded composite hydrogel according to claim 1, characterized in that: The cross-linking agent is N,N-methylenebisacrylamide, the initiator is N,N,N',N'-tetramethylethylenediamine, and the free radical initiator is ammonium persulfate. 9 . An Ag-MOFs-loaded composite hydrogel prepared by the method for preparing an Ag-MOFs-loaded composite hydrogel according to any one of claims 1 to 8 .

10. Use of the Ag-MOFs loaded composite hydrogel according to claim 9 in the preparation of antibacterial dressings.

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