Preparation method and application of antibacterial composite hydrogel

Abstract

The invention belongs to the technical field of high polymer materials, and particularly discloses a preparation method and application of antibacterial composite hydrogel, the preparation method comprises the following steps: (1) dissolving gallic acid and nano-selenium in a nano-cellulose suspension, and uniformly stirring to obtain a GA / CNC / SeNPs aqueous solution; (2) adding a cross-linking agent, a monomer, deionized water and a photoinitiator into the aqueous solution obtained in the step (1), and fully stirring; and (3) pouring the solution obtained in the step (2) into a mold, and carrying out ultraviolet radiation reaction to obtain the antibacterial composite hydrogel. The gallic acid, the acrylamide, the nano-selenium and the nano-cellulose are compounded to prepare the antibacterial multifunctional hydrogel, so that the mechanical strength of the hydrogel is reserved, and the antibacterial functions of the gallic acid and the nano-selenium are combined, so that an antibacterial substance with strength is formed; the method has a good application prospect in preparation of antibacterial materials in the field of biomedicine.

Description

Technical Field

[0001] The invention belongs to the technical field of polymer materials, relates to the preparation of medical hydrogel, and particularly to a preparation method and application of an antibacterial composite hydrogel. Background Art

[0002] Hydrogel is a highly hydrophilic three-dimensional network structure material, which can have a very high water content depending on its degree of cross-linking. Generally speaking, hydrogels can be formed by physical cross-linking and chemical cross-linking. Hydrogels have excellent biocompatibility and are widely used in the biomedical field. Hydrogels are ideal dressing materials that can keep the wound environment moist, cool the wound surface, and allow gas exchange. In particular, injectable hydrogels can encapsulate drugs in situ, fill wounds of various shapes, and integrate multiple functions such as anti-oxidation, hemostasis, and tissue adhesion. As a good antibacterial material, hydrogels can be used with a variety of antibacterial agents to achieve antibacterial treatment. Hydrogels have the characteristics of efficient loading and effective release of drugs and antibacterial agents, and have significant advantages in antibacterial materials, thereby greatly improving the utilization rate of antibacterial agents and reducing the toxic effects of antibacterial agents on cells.

[0003] Early hydrogels were mainly used for medical dressings and wound dressings. With the increasing understanding of bacterial infections and cross-infections, researchers began to explore how to add antimicrobial agents to hydrogels. Hydrogels loaded with metal ions and metal oxide nanoparticles can not only enhance the antibacterial properties, but also maintain antibacterial activity for a long time, reducing the possibility of bacteria developing drug resistance. However, the strength properties of the gel material also affect its application. How to develop an antibacterial substance with both strength and antibacterial properties will become a new research direction. Summary of the invention

[0004] In view of the deficiencies in the prior art, the purpose of the present invention is to provide a method for preparing an antibacterial composite hydrogel. The present invention composites gallic acid, acrylamide, nano-selenium and nano-cellulose to prepare an antibacterial and antioxidant multifunctional hydrogel, which not only retains the mechanical strength of the hydrogel, but also combines the antibacterial functions of gallic acid and nano-selenium, thereby forming an antibacterial substance with both strength and good application prospects in the preparation of antibacterial materials in the biomedical field.

[0005] The present invention is achieved through the following technical solutions:

[0006] A method for preparing an antibacterial composite hydrogel comprises the following steps:

[0007] (1) Dissolving gallic acid (GA) and selenium nanoparticles (SeNPs) in a suspension of CNC nanoparticles and stirring to obtain a GA / CNC / SeNPs aqueous solution;

[0008] (2) taking appropriate amounts of a crosslinking agent, a monomer, deionized water and a photoinitiator, adding them to the aqueous solution obtained in step (1), and stirring to obtain a fully mixed solution;

[0009] (3) pouring the solution obtained in step (2) into a mold, placing it in a UV box for UV irradiation reaction, and obtaining an antibacterial composite hydrogel.

[0010] A further improvement of the present invention is:

[0011] The nanocellulose suspension needs to be adjusted to pH 7.5-8.5 using a Tris buffer solution.

[0012] Furthermore, in the GA / CNC / SeNPs aqueous solution, the concentration of gallic acid is 1.02-2.04 mg / mL, and the concentration of nano-selenium is 3-8 mg / ml.

[0013] Furthermore, the stirring time in step (1) is 1 to 3 hours.

[0014] Furthermore, the mass ratio of the crosslinking agent, monomer, deionized water and photoinitiator in step (2) is 0.004-0.034:1.49-11.92:2-6:0.0894.

[0015] Furthermore, the crosslinking agent is N,N'-methylenebisacrylamide (MBA), the monomer is acrylamide (AM), and the photoinitiator is 2-carboxy-4'-(2-hydroxyethoxy)-2-methylpropiophenone.

[0016] Furthermore, in step (3), the power of ultraviolet irradiation is 1.4-1.8Kw, and the time is 30-60min.

[0017] A further improvement of the present invention is:

[0018] Protect the antibacterial composite hydrogel prepared by the above method.

[0019] A further improvement of the present invention is:

[0020] The application of the above antibacterial composite hydrogel in the preparation of antibacterial materials in the biomedical field.

[0021] Compared with the prior art, the present invention has the following beneficial effects:

[0022] The present invention prepares a multifunctional antibacterial and antioxidant hydrogel by compounding gallic acid, acrylamide, nano-selenium and nano-cellulose, which not only retains the mechanical strength of the hydrogel, but also combines the antibacterial functions of gallic acid and nano-selenium, thereby forming a composite hydrogel with good mechanical tensile performance and antibacterial performance, which has good application prospects in the preparation of antibacterial materials in the biomedical field. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] Figure 1 The morphology, structure and characterization analysis diagrams of the hydrogels prepared in Example 1 and Comparative Examples 1 and 2;

[0024] Figure 2 The swelling study and conductivity test results of the hydrogels prepared in Example 1 and Example 2 are shown;

[0025] Figure 3 The mechanical properties of the antibacterial composite hydrogels prepared in Examples 1 to 4;

[0026] Figure 4 The antibacterial effect diagram of the hydrogel prepared in Example 1 and Comparative Examples 1 and 2. DETAILED DESCRIPTION

[0027] The present invention is described in detail below in conjunction with specific embodiments.

[0028] Example 1: Preparation of antibacterial composite hydrogel

[0029] (1) Weigh 0.51 g of GA and 50 mg of SeNPs and dissolve them in 100 ml of purchased CNC aqueous solution (solid content 1%) adjusted to pH 8.0 with Tris buffer solution. Stir for about 2 h to fully dissolve GA and SeNPs to obtain a GA / CNC / SeNPs aqueous solution, which is diluted with deionized water to a GA concentration of 1.28 mg / mL.

[0030] (2) Take 0.01225g of MBA crosslinker, 5.96g of AM, 5g of deionized water, and 0.0894g of photoinitiator 2-carboxyl-4'-(2-hydroxyethoxy)-2-methylpropiophenone, add them to the diluted GA / CNC / SeNPs aqueous solution, use a magnetic stirrer to make it completely and evenly mixed, pour the mixed solution into a mold and tighten it with a clamp, place it in a UV box for thermal reaction, use 1.6kW UV curing polymerization method to react for 45 minutes, and form GA / CNCSeNPs hydrogel after curing. During the reaction process, GA, SeNPs and crosslinker will react to form a hydrogel network structure to obtain a hydrogel. After the hydrogel is formed, take out the hydrogel, rinse and soak it with deionized water for multiple times to remove unreacted monomers and water-soluble impurities, and finally obtain an antibacterial composite hydrogel.

[0031] Comparative Example 1: Preparation of CNC hydrogel

[0032] In this example, GA and SeNPs were not added, and other operations were basically the same as in Example 1 to prepare CNC hydrogel.

[0033] Comparative Example 2: Preparation of GA / CNC hydrogel

[0034] In this example, SeNPs were not added, and other operations were basically the same as in Example 1 to prepare GA / CNC hydrogel.

[0035] The hydrogels prepared in Example 1 and Comparative Examples 1 and 2 were characterized by SEM, FTIR, XRD, and the conductive properties were tested. The results are as follows: Figure 1 As shown, Figure 1 A is a schematic diagram of twisting, knotting and stretching of the antibacterial composite hydrogel of the present invention; Figure 1 B. Figure 1 C is the SEM and SEM-Mapping of the antibacterial composite hydrogel of the present invention. The distribution of CNC and SeNPs in the antibacterial composite hydrogel of the present invention was studied by SEM-Mapping. The results show that C, N, Se and O are distributed evenly in the hydrogel ( Figure 1 B, right), and the number of C, N, and O elements is large and the brightness is high, so the C, N, and O elements are high in SeNPs / GA / CNC content ( Figure 1 C). Figure 1 D is a schematic diagram of the skin fitting of the antibacterial composite hydrogel of the present invention.

[0036] The functional groups attached to the surface of GA / CNC hydrogel and GA / CNC / SeNPs hydrogel were determined by Fourier transform infrared spectroscopy. Figure 1 E). Compared with CNC hydrogel, at 2825.1 cm -1 、3375.7cm -1 and 1615.4cm -1 There are strong peaks, which are related to the stretching vibrations of CH, OH and C=O respectively.

[0037] XRD patterns of GA / CNC / SeNPs synthesized by analytical chemistry ( Figure 1 F), it was observed that there was an inconspicuous broad peak between 2θ=15.8° and 2θ=27.7° for CNC hydrogel, indicating that it was an amorphous structure; GA / CNC and GA / CNC / SeNPs both had obvious peaks at 2θ=12.1° and 2θ=28.99°, but the other lattice planes of the two could also be observed to have rich spectral line characteristics through the XRD diagram, and GA / CNC hydrogel and GA / CNC / SeNPs hydrogel existed in a crystalline structure. The calculated crystallinity of GA / CNC was 68.12%, and the crystallinity of GA / CNC / SeNPs was 27.4%, and the crystallization effect of GA / CNC hydrogel was better.

[0038] Example 2: Preparation of antibacterial composite hydrogel

[0039] In this example, the GA / CNC / SeNPs aqueous solution was diluted to GA concentrations of 1.02 mg / mL, 1.53 mg / mL, 1.79 mg / mL, and 2.04 mg / mL, respectively. The other operations were basically the same as in Example 1 to prepare antibacterial composite hydrogels.

[0040] The hydrogels prepared in Example 1 and Example 2 were subjected to swelling studies and conductivity tests. The results are shown in Figure 2 ,exist Figure 2 In A, the results of the swelling study showed that the hydrogel prepared under the conditions of AM 5.96g, MBA 0.01225 g, and GA concentration of 1.53 mg / mL had a maximum swelling rate of 1499.41% after 96.0h, showing excellent swelling performance. Through systematic research and regulation, the swelling properties of the hydrogel can be effectively improved.

[0041] exist Figure 2 In B, when the GA concentration is 1.02 mg / mL, the conductivity is the largest, with a value of 0.065 mS / cm, while when the GA concentration is 1.53 mg / mL, the conductivity is 0.035 mS / cm, indicating that the conductivity decreases with the increase of GA concentration.

[0042] Example 3: Preparation of antibacterial composite hydrogel

[0043] In this embodiment, the added amounts of MBA are 4.175 mg, 8.35 mg, 16.7 mg, 20.875 mg, 25.05 mg, 29.23 mg, and 33.4 mg, respectively. Other operations are basically the same as in Example 1, and antibacterial composite hydrogels are prepared respectively.

[0044] Example 4: Preparation of antibacterial composite hydrogel

[0045] In this embodiment, the added amounts of AM were 1.94 g, 2.98 g, 4.47 g, 7.45 g, 8.94 g, 10.43 g, and 11.92 g, respectively. The other operations were basically the same as those in Example 1, and antibacterial composite hydrogels were prepared respectively.

[0046] Typical tensile tests were performed on the antibacterial composite hydrogels prepared in Examples 1 to 4. The results are shown in FIG. Figure 3 As shown, Figure 3 A is the stretching of GA hydrogels with different concentrations. Figure 3 B is the stretching of acrylamide hydrogels with different masses. Figure 3 C is the stretching of MBA hydrogels with different masses. Figure 3 D is the toughness and elastic modulus of hydrogels with different concentrations; Figure 2 E is 600% strain GA 1.28 / CNC / SeNPs hydrogel multi-cycle stretching.

[0047] Example 5: Antibacterial performance test

[0048] The antibacterial properties of the hydrogels prepared in Example 1 and Comparative Examples 1 and 2 were tested according to the following steps: Staphylococcus aureus CICC 10201 and Escherichia coli CICC 10389 colonies were inoculated into 5 mL LB test tubes and cultured at 37°C and 180 rpm for 12 h. 600 Adjust to 0.6, take 50 μL and apply it to the LB plate. Take 10 μL of CNC, GA / CNC, GA / CNC / SeNPs and spot them on filter paper with a diameter of 3 mm, and place them on the plate containing the above bacteria and culture them at 37℃ for 12 hours. Observe the shape and size of the inhibition zone. The results are as follows: Figure 4 And as shown in Table 1.

[0049] Figure 4 The antibacterial results of the hydrogels prepared in Example 1 and Comparative Examples 1 and 2 against Staphylococcus aureus CICC10201 and Escherichia coli CICC 10389 are shown in FIG. Figure 3 The results showed that compared with the blank control group, gallic acid had a more obvious antibacterial effect. After SeNPs were added to the gallic acid antibacterial and antioxidant multifunctional hydrogel, its antibacterial effect was significantly improved.

[0050] Table 1 Antibacterial results of GA hydrogel

[0051]

[0052] ND: Not detected. a: Inner circle area; b: Outer circle area.

[0053] The above embodiments are only for illustrating the technical concept and features of the present invention, and their purpose is to enable people familiar with the technology to understand the content of the present invention and implement it accordingly, and they cannot be used to limit the protection scope of the present invention. Any equivalent transformation or modification made according to the spirit of the present invention should be included in the protection scope of the present invention.

Claims

1. A method for preparing an antibacterial composite hydrogel, characterized in that: The following steps are involved: (1) dissolving gallic acid and nano-selenium in a nanocellulose suspension and stirring to obtain a GA / CNC / SeNPs aqueous solution; (2) taking appropriate amounts of a crosslinking agent, a monomer, deionized water and a photoinitiator, adding them to the aqueous solution obtained in step (1), and stirring to obtain a fully mixed solution; (3) pouring the solution obtained in step (2) into a mold, placing it in a UV box for UV irradiation reaction, and obtaining an antibacterial composite hydrogel.

2. The method for preparing an antibacterial composite hydrogel according to claim 1, characterized in that: The nanocellulose suspension needs to be adjusted to pH 7.5-8.5 using a Tris buffer solution.

3. The method for preparing an antibacterial composite hydrogel according to claim 1, characterized in that: In the GA / CNC / SeNPs aqueous solution, the concentration of gallic acid is 1.02-2.04 mg / mL, and the concentration of nano-selenium is 3-8 mg / ml.

4. The method for preparing an antibacterial composite hydrogel according to claim 1, characterized in that: The stirring time in step (1) is 1 to 3 hours.

5. The method for preparing an antibacterial composite hydrogel according to claim 1, characterized in that: The mass ratio of the crosslinking agent, monomer, deionized water and photoinitiator described in step (2) is 0.004-0.034:1.49-11.92:2-6:0.0894.

6. The method for preparing an antibacterial composite hydrogel according to claim 1, characterized in that: The crosslinking agent is N,N'-methylenebisacrylamide, the monomer is acrylamide, and the photoinitiator is 2-carboxyl-4'-(2-hydroxyethoxy)-2-methylpropiophenone.

7. The method for preparing an antibacterial composite hydrogel according to claim 1, characterized in that: In step (3), the power of ultraviolet irradiation is 1.4-1.8Kw, and the time is 30-60min.

8. The antibacterial composite hydrogel prepared by the method according to any one of claims 1 to 7.

9. Use of the antibacterial composite hydrogel according to claim 8 in preparing antibacterial materials in the biomedical field.

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