Preparation method and application of cellulose antibacterial hydrogel

Abstract

The invention relates to the technical field of antibacterial hydrogels, and discloses a preparation method and application of cellulose antibacterial hydrogels. The invention obtains cellulose antibacterial hydrogels by adding intermediate 2, tertiary amine polymer, benzyl chloride and epichlorohydrin into a solvent for reaction. Intermediate 1 and hexamethyldisilazane (amine) alkane undergo addition reaction to introduce tertiary amine to obtain intermediate 2; intermediate 3 and di(dimethylamino)methylvinylsilane undergo copolymerization reaction to obtain tertiary amine polymer; finally, the tertiary amine in the tertiary amine polymer and the tertiary amine in the intermediate 2 generate a large amount of quaternary ammonium salts under the action of benzyl chloride, and the hyperbranched structure increases the degree of substitution of the quaternary ammonium salts, so that the quaternary ammonium salts have better antibacterial effects.

Description

Technical Field

[0001] The invention relates to the technical field of antibacterial hydrogels, in particular to a preparation method and application of cellulose antibacterial hydrogels. Background Art

[0002] Cellulose has the advantages of good biocompatibility, low cost, easy availability, and degradability, and has a wide range of applications in antibacterial applications. Hydrogels can be divided into natural polymer hydrogels and synthetic polymer hydrogels. Natural polymer hydrogels are degradable and highly safe. Synthetic polymers are easy to synthesize industrially and difficult to degrade. In recent years, harmful microorganisms such as bacteria have brought great harm to humans. How to avoid this phenomenon is the key to solving the problem. For example, the document "Construction of new "hyperbranched" cellulose-based functional materials and their antibacterial properties" is based on the excellent structural characteristics and good functional properties of dendritic polymers. This paper uses the method of terminal amino 0-generation polyamidoamine (PAMAM) grafted with oxidized cellulose to prepare a new type of cellulose-based polymer with good antibacterial properties. Therefore, it is applied to the present invention to synthesize a hydrogel with antibacterial effects. Summary of the invention

[0003] 1. Technical issues to be resolved

[0004] In view of the deficiencies in the prior art, the present invention provides a method for preparing and applying a cellulose antibacterial hydrogel, which has a good antibacterial effect.

[0005] (II) Technical solution

[0006] To achieve the above object, the present invention provides the following technical solution: a method for preparing an antibacterial cellulose hydrogel, wherein the method for preparing the antibacterial cellulose hydrogel is:

[0007] (1) dispersing microcrystalline cellulose into a reactor filled with distilled water, then adding 18-20% by mass sulfuric acid solution to adjust the pH to 2-2.3, stirring for 20-26 minutes, and then continuing to add sodium periodate, and reacting at 25-30° C. in a dark environment for 8-10 hours. After the reaction, adding ethylene glycol for washing, filtering, then washing with water for 2-3 times, washing with anhydrous ethanol for 1-2 times, and vacuum drying at 25-35° C. for 20-25 hours to obtain dialdehyde cellulose;

[0008] (2) Dispersing dialdehyde cellulose in anhydrous ethanol solvent, introducing nitrogen protection, then adjusting the temperature to 65-75° C., continuing to add PAMAM ethanol solution to the reaction system, stirring for 3-5 hours, and then centrifuging, filtering, washing with anhydrous ethanol, and drying at 30-35° C. for 20-25 hours to obtain intermediate 1;

[0009] (3) adding intermediate 1 and hexamethyldisilazane to N,N-dimethylformamide solvent, introducing nitrogen protection, and then adding chloroplatinic acid catalyst thereto, reacting at 50-70° C. for 40-70 min, and then performing reduced pressure distillation after completion, filtering and drying to obtain intermediate 2;

[0010] (4) PAMAM and acryloyl chloride were added to the reactor, stirred and dissolved, and triethylamine catalyst was added thereto, and the reaction was carried out at 50-80° C. for 6-10 hours. After the reaction was completed, the mixture was distilled under reduced pressure, washed with petroleum ether, filtered, and dried to obtain intermediate 3;

[0011] (5) adding intermediate 3 and di(dimethylamino)methylvinylsilane to N,N-dimethylformamide solvent, introducing nitrogen protection, adding ammonium persulfate initiator, reacting at 60-80° C. for 3-5 hours, filtering after the reaction, washing with deionized water, and drying to obtain a tertiary amine polymer;

[0012] (6) Add 8-12 parts by weight of intermediate 2, 10-15 parts by weight of tertiary amine polymer, 18-25 parts by weight of benzyl chloride, and 6-12 parts by weight of epichlorohydrin to N,N-dimethylformamide solvent, react at 90-110° C. for 8-12 hours, distill under reduced pressure after the reaction, and wash with ethanol to obtain cellulose antibacterial hydrogel.

[0013] Preferably, the mass ratio of microcrystalline cellulose, sulfuric acid and sodium periodate in (1) is 1:0.2-0.4:1.2-1.3.

[0014] Preferably, the mass ratio of dialdehyde cellulose to PAMAM in (2) is 1:1.1-1.3.

[0015] Preferably, the mass ratio of the intermediate 1, hexamethyldisilazane, and chloroplatinic acid catalyst in (3) is 1.2-1.5:1:0.01-0.02.

[0016] Preferably, the mass ratio of PAMAM, acryloyl chloride and triethylamine catalyst in (4) is 1:1.5-2:0.03-0.05.

[0017] Preferably, the mass ratio of the intermediate 3, di(dimethylamino)methylvinylsilane and ammonium persulfate initiator in (5) is 1.3-1.6:1:0.01-0.04.

[0018] Preferably, the antibacterial cellulose hydrogel is used in the field of antibacterial medical care and hygiene.

[0019] (III) Beneficial technical effects

[0020] The present invention adds intermediate 2, tertiary amine polymer, benzyl chloride and epichlorohydrin into a solvent for reaction to obtain the cellulose antibacterial hydrogel.

[0021] Intermediate 1 and hexamethyldisilazane are subjected to addition reaction to introduce tertiary amine to obtain intermediate 2; intermediate 3 and di(dimethylamino)methylvinylsilane are subjected to copolymerization reaction to obtain a tertiary amine polymer; finally, the tertiary amine in the tertiary amine polymer and the tertiary amine in intermediate 2 generate a large amount of quaternary ammonium salt under the action of benzyl chloride, and the hyperbranched structure increases the substitution degree of the quaternary ammonium salt, so that it has a good antibacterial effect; it has good antibacterial properties against Escherichia coli, Streptococcus aureus, and Candida albicans, and has good application prospects in the field of antibacterial medical and health care. DETAILED DESCRIPTION

[0022] Preparation of PAMAM: Reference "Construction of new "hyperbranched" cellulose-based functional materials and study of their antibacterial properties".

[0023] Example 1

[0024] (1) 1 g of microcrystalline cellulose was dispersed in a reactor containing 80 ml of distilled water, and then 0.4 g of 18% sulfuric acid was added to adjust the pH of the solution to 2, and stirred for 20 min, and then 2.4 g of sodium periodate was added, and the reaction was shielded from light at 25° C. for 8 h. After the reaction, 60 ml of ethylene glycol was added for washing, and the mixture was filtered, washed with water twice, washed with anhydrous ethanol once, and vacuum dried at 25° C. for 20 h to obtain dialdehyde cellulose;

[0025] (2) Disperse 2 g of dialdehyde cellulose in 75 ml of anhydrous ethanol solvent, introduce nitrogen protection, and then adjust the temperature to 65° C., continue to add 40 ml of ethanol solution of 2.2 g of PAMAM to the reaction system, stir for 3 h, and then centrifuge, filter, wash with anhydrous ethanol, and dry at 30° C. for 20 h to obtain intermediate 1;

[0026] (3) Add 1.2 g of intermediate 1 and 1 g of hexamethyldisilazane to 65 ml of N,N-dimethylformamide solvent, introduce nitrogen protection, then add 0.01 g of chloroplatinic acid catalyst, react at 50° C. for 40 min, and then distill under reduced pressure, filter and dry to obtain intermediate 2;

[0027] (4) 1 g of PAMAM and 1.5 g of acryloyl chloride were added to the reactor, stirred and dissolved, and 0.03 g of triethylamine catalyst was added thereto, and the reaction was carried out at 50° C. for 6 h. After the reaction, the reaction was carried out under reduced pressure distillation, washed with petroleum ether, filtered, and dried to obtain intermediate 3;

[0028] (5) 2.3 g of intermediate 3 and 1 g of di(dimethylamino)methylvinylsilane were added to 85 ml of N,N-dimethylformamide solvent, nitrogen was introduced, and 0.01 g of ammonium persulfate initiator was added. The mixture was reacted at 60° C. for 3 h. After the reaction, the mixture was filtered, washed with deionized water, and dried to obtain a tertiary amine polymer.

[0029] (6) 0.8 g of intermediate 2, 1 g of tertiary amine polymer, 1.8 g of benzyl chloride, and 0.6 g of epichlorohydrin were added to 95 ml of N,N-dimethylformamide solvent, and reacted at 90° C. for 8 h. After the reaction, the mixture was distilled under reduced pressure and washed with ethanol to obtain cellulose antibacterial hydrogel.

[0030] Example 2

[0031] (1) 2 g of microcrystalline cellulose was dispersed in a reactor containing 120 ml of distilled water, and then 0.8 g of 20% sulfuric acid was added to adjust the pH of the solution to 2.3, and stirred for 26 min, and then 2.6 g of sodium periodate was added, and the reaction was shielded from light at 30° C. for 10 h. After the reaction, 80 ml of ethylene glycol was added for washing, and the mixture was filtered, washed with water for 3 times, washed with anhydrous ethanol for 2 times, and vacuum dried at 35° C. for 25 h to obtain dialdehyde cellulose;

[0032] (2) Disperse 3 g of dialdehyde cellulose in 90 ml of anhydrous ethanol solvent, introduce nitrogen protection, then adjust the temperature to 75°C, continue to add 70 ml of 3.9 g of PAMAM ethanol solution to the reaction system, stir for 5 h, and then centrifuge, filter, wash with anhydrous ethanol, and dry at 35°C for 25 h to obtain intermediate 1;

[0033] (3) Add 1.5 g of intermediate 1 and 1 g of hexamethyldisilazane to 90 ml of N,N-dimethylformamide solvent, introduce nitrogen protection, then add 0.02 g of chloroplatinic acid catalyst, react at 70° C. for 70 min, and then distill under reduced pressure, filter and dry to obtain intermediate 2;

[0034] (4) 1 g of PAMAM and 2 g of acryloyl chloride were added to the reactor, stirred and dissolved, and 0.05 g of triethylamine catalyst was added thereto, and the reaction was carried out at 80° C. for 10 h. After the reaction, the reaction was carried out under reduced pressure distillation, washed with petroleum ether, filtered, and dried to obtain intermediate 3;

[0035] (5) 3.4 g of intermediate 3 and 2 g of di(dimethylamino)methylvinylsilane were added to 120 ml of N,N-dimethylformamide solvent, nitrogen was introduced, and 0.04 g of ammonium persulfate initiator was added. The mixture was reacted at 80° C. for 5 h. After the reaction, the mixture was filtered, washed with deionized water, and dried to obtain a tertiary amine polymer.

[0036] (6) 1.2 g of intermediate 2, 1.5 g of tertiary amine polymer, 2.5 g of benzyl chloride, and 1.2 g of epichlorohydrin were added to 110 ml of N,N-dimethylformamide solvent, and reacted at 110° C. for 12 h. After the reaction, the mixture was distilled under reduced pressure and washed with ethanol to obtain a cellulose antibacterial hydrogel.

[0037] Example 3

[0038] (1) 1.5 g of microcrystalline cellulose was dispersed in a reactor containing 100 ml of distilled water, and then 0.6 g of 19% sulfuric acid was added to adjust the pH of the solution to 2.15, and the mixture was stirred for 23 min, and then 2.5 g of sodium periodate was added, and the mixture was reacted at 27.5° C. in a dark environment for 9 h. After the reaction, 70 ml of ethylene glycol was added for washing, and the mixture was filtered, washed with water twice, washed with anhydrous ethanol twice, and dried in vacuum at 30° C. for 22.5 h to obtain dialdehyde cellulose;

[0039] (2) Disperse 2.5 g of dialdehyde cellulose in 82.5 ml of anhydrous ethanol solvent, introduce nitrogen protection, and then adjust the temperature to 70°C. Continue to add 3.05 g of PAMAM ethanol solution (55 ml) to the reaction system, stir for 4 h, and then centrifuge, filter, wash with anhydrous ethanol, and dry at 32.5°C for 22.5 h to obtain intermediate 1;

[0040] (3) Add 1.35 g of intermediate 1 and 1 g of hexamethyldisilazane to 77.5 ml of N,N-dimethylformamide solvent, introduce nitrogen protection, then add 0.015 g of chloroplatinic acid catalyst, react at 60° C. for 55 min, and then perform vacuum distillation, filter and dry to obtain intermediate 2;

[0041] (4) 1 g of PAMAM and 1.75 g of acryloyl chloride were added to the reactor, stirred and dissolved, and 0.04 g of triethylamine catalyst was added thereto, and the reaction was carried out at 65° C. for 8 h. After the reaction, the reaction was carried out under reduced pressure distillation, washed with petroleum ether, filtered, and dried to obtain intermediate 3;

[0042] (5) 2.85 g of intermediate 3 and 1.5 g of di(dimethylamino)methylvinylsilane were added to 102.5 ml of N,N-dimethylformamide solvent, nitrogen was introduced, and 0.025 g of ammonium persulfate initiator was added. The mixture was reacted at 70° C. for 4 h. After the reaction, the mixture was filtered, washed with deionized water, and dried to obtain a tertiary amine polymer.

[0043] (6) 1.0 g of intermediate 2, 1.25 g of tertiary amine polymer, 2.15 g of benzyl chloride, and 0.9 g of epichlorohydrin were added to 102.5 ml of N,N-dimethylformamide solvent, and reacted at 100 °C for 10 h. After the reaction, the mixture was distilled under reduced pressure and washed with ethanol to obtain cellulose antibacterial hydrogel.

[0044] Example 4

[0045] (1) 1 g of microcrystalline cellulose was dispersed in a reactor containing 80 ml of distilled water, and then 0.4 g of 18% sulfuric acid was added to adjust the pH of the solution to 2, and stirred for 20 min, and then 2.4 g of sodium periodate was added, and the reaction was shielded from light at 25° C. for 8 h. After the reaction, 60 ml of ethylene glycol was added for washing, and the mixture was filtered, washed with water twice, washed with anhydrous ethanol once, and vacuum dried at 25° C. for 20 h to obtain dialdehyde cellulose;

[0046] (2) Disperse 2 g of dialdehyde cellulose in 75 ml of anhydrous ethanol solvent, introduce nitrogen protection, and then adjust the temperature to 65° C., continue to add 40 ml of ethanol solution of 2.2 g of PAMAM to the reaction system, stir for 3 h, and then centrifuge, filter, wash with anhydrous ethanol, and dry at 30° C. for 20 h to obtain intermediate 1;

[0047] (3) Add 1.5 g of intermediate 1 and 1 g of hexamethyldisilazane to 90 ml of N,N-dimethylformamide solvent, introduce nitrogen protection, then add 0.02 g of chloroplatinic acid catalyst, react at 70° C. for 70 min, and then distill under reduced pressure, filter and dry to obtain intermediate 2;

[0048] (4) 1 g of PAMAM and 2 g of acryloyl chloride were added to the reactor, stirred and dissolved, and 0.05 g of triethylamine catalyst was added thereto, and the reaction was carried out at 80° C. for 10 h. After the reaction, the reaction was carried out under reduced pressure distillation, washed with petroleum ether, filtered, and dried to obtain intermediate 3;

[0049] (5) 2.85 g of intermediate 3 and 1.5 g of di(dimethylamino)methylvinylsilane were added to 102.5 ml of N,N-dimethylformamide solvent, nitrogen was introduced, and 0.025 g of ammonium persulfate initiator was added. The mixture was reacted at 70° C. for 4 h. After the reaction, the mixture was filtered, washed with deionized water, and dried to obtain a tertiary amine polymer.

[0050] (6) 1.0 g of intermediate 2, 1.25 g of tertiary amine polymer, 2.15 g of benzyl chloride, and 0.9 g of epichlorohydrin were added to 102.5 ml of N,N-dimethylformamide solvent, and reacted at 100 °C for 10 h. After the reaction, the mixture was distilled under reduced pressure and washed with ethanol to obtain cellulose antibacterial hydrogel.

[0051] Comparative Example 1

[0052] (1) 1.0 g of intermediate 2, 2.15 g of benzyl chloride, and 0.9 g of epichlorohydrin were added to 102.5 ml of N,N-dimethylformamide solvent, and reacted at 100° C. for 10 h. After the reaction, the mixture was distilled under reduced pressure and washed with ethanol to obtain a cellulose antibacterial hydrogel.

[0053] The cellulose antibacterial hydrogel was dried, pressed and cut into hydrogel samples with a diameter of 4 cm and a thickness of 2 mm. Staphylococcus aureus, Escherichia coli or Candida albicans were used as test strains. 0.5 mL of the bacterial suspension of the test strain (concentration of 1×106 CFU / mL) was transferred into a sterile culture dish containing beef extract peptone medium. Then the hydrogel sample was attached to the surface of the culture medium and cultured in a constant temperature incubator at 37°C for 24 h. After culture, the diameter of the inhibition zone was measured. The test results are shown in Table 1.

[0054] Table 1: Antimicrobial testing.

[0055]

[0056]

[0057] It can be seen from Table 1 that Examples 1-4 of the present invention have larger inhibition zone diameters than Comparative Example 1, indicating better antibacterial effects.

[0058] The preferred embodiments of the present invention disclosed above are only used to help illustrate the present invention. The preferred embodiments do not describe all the details in detail, nor do they limit the invention to the specific implementation methods described. Obviously, many modifications and changes can be made according to the content of this specification. This specification selects and specifically describes these embodiments in order to better explain the principles and practical applications of the present invention, so that those skilled in the art can understand and use the present invention well. The present invention is limited only by the claims and their full scope and equivalents.

Claims

1. A method for preparing an antibacterial cellulose hydrogel, characterized in that: The preparation method of the antibacterial cellulose hydrogel is as follows: (1) dispersing microcrystalline cellulose into a reactor filled with distilled water, then adding 18-20% by mass sulfuric acid solution to adjust the pH to 2-2.3, stirring for 20-26 minutes, and then continuing to add sodium periodate, and reacting at 25-30° C. in a dark environment for 8-10 hours. After the reaction, adding ethylene glycol for washing, filtering, then washing with water for 2-3 times, washing with anhydrous ethanol for 1-2 times, and vacuum drying at 25-35° C. for 20-25 hours to obtain dialdehyde cellulose; (2) Dispersing dialdehyde cellulose in anhydrous ethanol solvent, introducing nitrogen protection, then adjusting the temperature to 65-75° C., continuing to add PAMAM ethanol solution to the reaction system, stirring for 3-5 hours, and then centrifuging, filtering, washing with anhydrous ethanol, and drying at 30-35° C. for 20-25 hours to obtain intermediate 1; (3) adding intermediate 1 and hexamethyldisilazane to N,N-dimethylformamide solvent, introducing nitrogen protection, and then adding chloroplatinic acid catalyst thereto, reacting at 50-70° C. for 40-70 min, and then performing reduced pressure distillation after completion, filtering and drying to obtain intermediate 2; (4) PAMAM and acryloyl chloride were added to the reactor, stirred and dissolved, and triethylamine catalyst was added thereto, and the reaction was carried out at 50-80° C. for 6-10 hours. After the reaction was completed, the mixture was distilled under reduced pressure, washed with petroleum ether, filtered, and dried to obtain intermediate 3; (5) adding intermediate 3 and di(dimethylamino)methylvinylsilane to N,N-dimethylformamide solvent, introducing nitrogen protection, adding ammonium persulfate initiator, reacting at 60-80° C. for 3-5 hours, filtering after the reaction, washing with deionized water, and drying to obtain a tertiary amine polymer; (6) adding 8-12 parts by weight of intermediate 2, 10-15 parts by weight of tertiary amine polymer, 18-25 parts by weight of benzyl chloride, and 6-12 parts by weight of epichlorohydrin to N,N-dimethylformamide solvent, reacting at 90-110° C. for 8-12 hours, distilling under reduced pressure after the reaction, and washing with ethanol to obtain a cellulose antibacterial hydrogel; The mass ratio of microcrystalline cellulose, sulfuric acid and sodium periodate in (1) is 1:0.2-0.4:1.2-1.3; The mass ratio of dialdehyde cellulose to PAMAM in (2) is 1:1.1-1.3; The mass ratio of the intermediate 1, hexamethyldisilazane, and chloroplatinic acid catalyst in (3) is 1.2-1.5:1:0.01-0.02; The mass ratio of PAMAM, acryloyl chloride and triethylamine catalyst in (4) is 1:1.5-2:0.03-0.05; The mass ratio of the intermediate 3, di(dimethylamino)methylvinylsilane and ammonium persulfate initiator in (5) is 1.7:1:0.02.

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