Functional material doped with silver modified calcium peroxide nanoparticles as well as preparation method and application of functional material

Abstract

The invention provides a functional material doped with silver modified calcium peroxide nanoparticles as well as a preparation method and application of the functional material, and belongs to the technical field of hydrogel material preparation and antibacterial materials. According to the functional material, oxidized dextran and carboxymethyl chitosan are used as a skeleton structure to prepare Schiff base hydrogel, and silver-modified calcium peroxide nanoparticles are doped in the Schiff base hydrogel; the silver-modified calcium peroxide nanoparticles are obtained by modifying the surface of calcium peroxide with silicon dioxide and then modifying silver nanoparticles. The functional material doped with the silver modified calcium peroxide nanoparticles has excellent antibacterial activity and long-acting antibacterial ability, has long-acting and excellent bactericidal activity on typical gram-positive bacteria and gram-negative bacteria, and has good antibacterial application in a microenvironment with bacterial infection.

Description

Technical Field

[0001] The invention belongs to the technical field of hydrogel material preparation and antibacterial material, and specifically relates to a functional material of silver-doped modified calcium peroxide nanoparticles and a preparation method and application thereof. Background Art

[0002] Bacterial infection is a major challenge facing humans. Conventional antibiotic treatment can easily cause bacteria to develop drug resistance, which further increases the infection rate and mortality rate. Existing antibacterial materials cannot balance antibacterial activity and persistent antibacterial activity, and cannot achieve efficient and long-lasting antibacterial effects. Therefore, it is necessary to design an antibacterial material with efficient and long-lasting antibacterial effects. Environmentally responsive hydrogels have become a new direction for the development of antibacterial materials in the future due to their high biosafety, degradability, and non-toxicity. How to design antibacterial hydrogels with excellent antibacterial activity and long-lasting antibacterial ability has become a major challenge.

[0003] Calcium peroxide (CaO2) is a donor of hydrogen peroxide (H2O2), which can endow hydrogels with excellent bactericidal activity, but there is still a disadvantage of explosive release of H2O2, which limits its long-term antibacterial activity. Schiff base hydrogel is an excellent environmentally responsive antibacterial material with non-toxicity, high biosafety, degradability and drug delivery capabilities. In addition, the structure formed by non-covalent interactions such as electrostatics and hydrogen bonds between the abundant amino and carboxyl groups inside it has good dispersibility and stability for the loaded nanoparticles. Therefore, compared with hydrogels loaded with drugs by traditional methods, it can release drugs in a controlled manner and has high biosafety, but the rapid and irreversible consumption of calcium peroxide cannot achieve the long-term antibacterial ability of hydrogels.

[0004] Therefore, it is necessary to develop a Schiff base hydrogel with both excellent antibacterial activity and long-lasting antibacterial ability to achieve long-lasting and excellent bactericidal activity against typical Gram-positive bacteria and Gram-negative bacteria. Summary of the invention

[0005] In view of some deficiencies in the prior art, the present invention provides a functional material doped with silver-modified calcium peroxide nanoparticles, a preparation method and application thereof; the functional material uses oxidized dextran and carboxymethyl chitosan as a skeleton structure to prepare a Schiff base hydrogel, and dopes the Schiff base hydrogel with silver-modified calcium peroxide nanoparticles; the silver-modified calcium peroxide nanoparticles are obtained by modifying silica on the surface of calcium peroxide and then modifying silver nanoparticles; the functional material doped with silver-modified calcium peroxide nanoparticles has excellent antibacterial activity and long-lasting antibacterial ability, has long-lasting and excellent bactericidal activity against typical Gram-positive bacteria and Gram-negative bacteria, and has good antibacterial application in the microenvironment of bacterial infection.

[0006] In order to achieve the above technical objectives, the present invention adopts the following technical means: The present invention firstly provides a functional material doped with silver-modified calcium peroxide nanoparticles. The functional material dopes the silver-modified calcium peroxide nanoparticles in the network structure of Schiff base hydrogel through non-covalent interaction. The skeleton structure of the Schiff base hydrogel is oxidized dextran and carboxymethyl chitosan. The silver-modified calcium peroxide nanoparticles are obtained by loading the silver nanoparticles on core-shell type silica-modified calcium peroxide. In the core-shell type silica-modified calcium peroxide, the calcium peroxide is used as the core and the silica is used as the shell.

[0007] The present invention also provides a method for preparing the functional material of the above-mentioned silver-doped modified calcium peroxide nanoparticles, the preparation method comprising: (1) Preparation of silver-doped calcium peroxide nanoparticles: Calcium peroxide, ammonia water, tetraethyl orthosilicate and trimercaptopropyltrimethoxysilane are dispersed in ethanol, mixed evenly and reacted under stirring for 1, and centrifuged and dried after the reaction to obtain silica-modified calcium peroxide; Dispersing silica-modified calcium peroxide, silver ammonia solution, and oxidized dextran solution in deionized water in sequence and reacting them under stirring conditions for 2, centrifuging and drying after the reaction to obtain silver-doped calcium peroxide nanoparticles; (2) Preparation of functional materials of silver-doped calcium peroxide nanoparticles: The silver-doped calcium peroxide nanoparticles are dispersed in deionized water, and the oxidized dextran solution and carboxymethyl chitosan are added in sequence, and the mixture is rapidly stirred, poured into a mold, and allowed to stand to form a gel, thereby obtaining the functional material of the silver-doped calcium peroxide nanoparticles.

[0008] Preferably, in step (1), the usage ratio of calcium peroxide, ammonia water, tetraethyl orthosilicate and trimercaptopropyltrimethoxysilane is 10-30 mg; 1-4 mL; 0.1-0.8 mL; 0.1-0.8 mL.

[0009] Preferably, in step (1), the reaction 1 is carried out at room temperature for 8-12 hours.

[0010] Preferably, in step (1), the amount of silica-modified calcium peroxide, silver ammonia solution and oxidized dextran solution is 10-30 mg; 0.1-0.4 mL; 0.1-1 mL; wherein the concentration of the silver ammonia solution is 0.1-0.3 mol / L.

[0011] Preferably, in step (1), the reaction 2 is carried out under the following conditions: reacting at room temperature for 10-30 minutes.

[0012] Preferably, in step (2), the amount of oxidized dextran solution and silver-doped modified calcium peroxide nanoparticles used is 5-15 mL; 10-30 mg.

[0013] Preferably, in step (2), the amount of oxidized dextran solution and carboxymethyl chitosan used is 5-15 mL; 0.2-0.5 g.

[0014] The present invention also provides the application of the functional material of the silver-doped calcium peroxide nanoparticles modified in antibacterial applications.

[0015] Preferably, in the application, the antibacterial bacteria are Gram-positive bacteria and Gram-negative bacteria.

[0016] Preferably, the bacteria include Staphylococcus aureus and Escherichia coli.

[0017] Compared with the prior art, the present invention has the following beneficial effects: (1) The silver-doped calcium peroxide nanoparticles of the present invention have the advantages of sustained release of hydrogen peroxide and generation of free radicals through a Fenton-like reaction, and have outstanding physical and chemical properties such as long-term release of hydrogen peroxide and generation of free radicals. The present invention functionalizes the silver-doped calcium peroxide nanoparticles into Schiff base hydrogels, which can achieve controlled release of the loaded drugs, construct a long-term antibacterial mechanism of silver nanoparticles and hydroxyl free radicals, thereby reducing the problem of insufficient long-term antibacterial ability caused by nonspecific release of drugs, and improving the responsive release process of drugs, thereby effectively improving the long-term antibacterial activity of hydrogel materials.

[0018] (2) The functional material of silver-doped modified calcium peroxide nanoparticles described in the present invention combines the advantages of silver-doped modified calcium peroxide nanoparticles and Schiff base hydrogel. The present invention uses SiO2 to modify CaO2 to prepare silica-modified calcium peroxide, which can not only significantly improve the H2O2 release behavior, but also achieve long-term release of H2O2. In addition, the surface of the SiO2 shell modified by the silane coupling agent also has abundant thiol groups, which can form metal-sulfur covalent bonds with AgNPs, thereby modifying AgNPs on the surface of CaO2@SiO2 nanoparticles. CaO2 nanoparticles can continuously release H2O2 in a slightly acidic environment, and react with AgNPs to produce a Fenton-like reaction. • OH, achieving efficient bactericidal activity of nanoparticles.

[0019] (3) The functional material of the silver-doped calcium peroxide nanoparticles modified in the present invention can be used to fight against Staphylococcus aureus and Escherichia coli. It not only has a bactericidal rate of more than 99%, but also can release antibacterial activity for a long time. After three cycles, its antibacterial activity can still reach more than 95%. Compared with the performance of pure Schiff base hydrogel, the functional material of the silver-doped calcium peroxide nanoparticles modified in the present invention has significantly improved bactericidal rate and long-term antibacterial activity.

[0020] (4) The preparation process of the functional material of silver-doped calcium peroxide nanoparticles modified by the present invention is simple, the reaction is controllable, the raw materials are cheap and easy to obtain, the conditions are mild, and it has good industrial application value. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] Figure 1 Schematic diagram of the antibacterial activity of the functional material (CSAH-1) containing silver-modified calcium peroxide nanoparticles prepared in Example 1; the left picture is Staphylococcus aureus, and the right picture is Escherichia coli.

[0022] Figure 2 Schematic diagram of the antibacterial activity of the functional material (CSAH-2) containing silver-modified calcium peroxide nanoparticles prepared in Example 2; the left picture is Staphylococcus aureus, and the right picture is Escherichia coli.

[0023] Figure 3 Schematic diagram of the antibacterial activity of the functional material (CSAH-3) containing silver-modified calcium peroxide nanoparticles prepared in Example 3; the left picture is Staphylococcus aureus, and the right picture is Escherichia coli.

[0024] Figure 4 Schematic diagram of the antibacterial activity of the functional material (CSAH-4) containing silver-modified calcium peroxide nanoparticles prepared in Example 4; the left picture is Staphylococcus aureus, and the right picture is Escherichia coli.

[0025] Figure 5 Schematic diagram of the antibacterial activity of the functional material (CSAH-0) prepared in Comparative Example 1; the left picture is Staphylococcus aureus, and the right picture is Escherichia coli. DETAILED DESCRIPTION

[0026] The present invention is further described below in conjunction with the accompanying drawings and specific embodiments, but the protection scope of the present invention is not limited thereto. Obviously, the described embodiments are part of the embodiments of the present invention, rather than all of the embodiments. Based on the described embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work belong to the protection scope of the present invention.

[0027] Unless otherwise defined, technical or scientific terms used herein shall have the same meaning as commonly understood by one of ordinary skill in the art to which the invention belongs.

[0028] The Staphylococcus aureus (SHBCC D10842) and Escherichia coli (SHBCC D80515) involved in the following examples were purchased from Shanghai Collection of Microorganisms Center.

[0029] Example 1: Preparation of functional materials of silver-doped calcium peroxide nanoparticles (1) Preparation of materials: Oxidized dextran (ODEX) solution: Weigh 6 g of dextran and 6 g of sodium periodate and dissolve them in 100 mL of deionized water. Stir vigorously for 10 h at room temperature in the dark to obtain an orange-yellow solution. Dialyze and then freeze-dry at -90 °C to obtain oxidized dextran. Dissolve 2 g of oxidized dextran in 20 mL of deionized water to obtain an oxidized dextran solution (10 wt%).

[0030] Silver ammonia solution: Add 25%wt ammonia water dropwise into 0.2 mol / L silver nitrate solution, shaking while adding, until the generated precipitate is just redissolved to obtain a silver ammonia solution.

[0031] Calcium peroxide: Dissolve 4 g of calcium chloride and 4 g of polyvinyl pyrrolidone in 1000 mL of ethanol, then add 20 mL of hydrogen peroxide and 20 mL of ammonia water. Stir vigorously to react. After the reaction, a white suspension is obtained. Centrifuge at 10,000 rpm for 10 min and dry in vacuum at 60°C to obtain calcium peroxide.

[0032] (2) Preparation of silver-doped calcium peroxide nanoparticles: 30 mg of calcium peroxide, 3 mL of ammonia water, 0.1 mL of tetraethyl orthosilicate and 0.8 mL of trithiopropyltrimethoxysilane were dispersed in 30 mL of ethanol, added thereto, mixed evenly, and stirred at room temperature for 8 h. After the reaction, centrifuged and dried in vacuum at 60°C to obtain silica-modified calcium peroxide; 30 mg of silica-modified calcium peroxide was dispersed in 10 mL of deionized water, 0.2 mL of silver ammonia solution was added thereto and stirred to mix evenly, then 0.2 mL of oxidized dextran solution was added and reacted for 20 min under stirring conditions, and after the reaction was completed, the mixture was centrifuged and vacuum dried at 60°C to obtain silver-doped calcium peroxide nanoparticles; (3) Preparation of functional materials of silver-doped calcium peroxide nanoparticles: 30 mg of silver-doped calcium peroxide nanoparticles were dispersed in 10 mL of deionized water, and 12 mL of oxidized dextran solution and 0.3 g of carboxymethyl chitosan were added in sequence. The mixture was stirred rapidly, poured into a mold, and allowed to stand to form a gel, thereby obtaining the functional material of silver-doped calcium peroxide nanoparticles, which was recorded as CSAH-1.

[0033] In this example, the bactericidal activity of CSAH-1 against Staphylococcus aureus and Escherichia coli was also investigated at 37°C and pH 5.5. The test results are as follows: Figure 1 The test results show that the sterilization rates of CSAH-1 against Staphylococcus aureus and Escherichia coli are 99.9% and 99.8% respectively.

[0034] Example 2: Preparation of functional materials of silver-doped calcium peroxide nanoparticles In this example, the method described in Example 1 was used to prepare a functional material of silver-doped calcium peroxide nanoparticles, with the following differences: in step (3), the amount of tetraethyl orthosilicate was 0.2 mL, and the amount of trimercaptopropyltrimethoxysilane was 0.7 mL. The obtained functional material of silver-doped calcium peroxide nanoparticles was recorded as CSAH-2.

[0035] In this example, the bactericidal activity of CSAH-2 against Staphylococcus aureus and Escherichia coli was also investigated at 37°C and pH 5.5. The test results are shown in FIG. Figure 2 The test results show that the sterilization rates of CSAH-2 against Staphylococcus aureus and Escherichia coli are 99.8% and 99.6% respectively.

[0036] Example 3: Preparation of functional materials of silver-doped calcium peroxide nanoparticles In this example, the method described in Example 1 was used to prepare a functional material of silver-doped calcium peroxide nanoparticles, with the following differences: in step (3), the amount of tetraethyl orthosilicate was 0.3 mL, and the amount of trimercaptopropyltrimethoxysilane was 0.6 mL. The obtained functional material of silver-doped calcium peroxide nanoparticles was recorded as CSAH-3.

[0037] In this example, the bactericidal activity of CSAH-3 against Staphylococcus aureus and Escherichia coli was also investigated at 37°C and pH 5.5. The test results are as follows: Figure 3 The test results show that the sterilization rates of CSAH-3 against Staphylococcus aureus and Escherichia coli are 99.8% and 99.5% respectively.

[0038] Example 4: Preparation of functional materials of silver-doped calcium peroxide nanoparticles In this example, the method described in Example 1 was used to prepare a functional material of silver-doped calcium peroxide nanoparticles, with the following differences: in step (3), the amount of tetraethyl orthosilicate was 0.4 mL, and the amount of trimercaptopropyltrimethoxysilane was 0.5 mL. The obtained functional material of silver-doped calcium peroxide nanoparticles was recorded as CSAH-4.

[0039] In this example, the bactericidal activity of CSAH-4 against Staphylococcus aureus and Escherichia coli was also investigated at 37°C and pH 5.5. The test results are shown in FIG. Figure 4 The test results show that the sterilization rates of CSAH-4 against Staphylococcus aureus and Escherichia coli are 99.7% and 99.6% respectively.

[0040] Comparative Example 1: In this comparative example, a functional material CSAH-0 was prepared. The preparation method of the functional material CSAH-0 is as follows: Disperse 30 mg of calcium peroxide nanoparticles in 10 mL of deionized water, add 12 mL of oxidized dextran solution and 0.3 g of carboxymethyl chitosan in sequence, stir rapidly, pour into a mold, and let stand to form a gel to obtain the functional material CSAH-0.

[0041] In this example, the bactericidal activity of CSAH-0 against Staphylococcus aureus and Escherichia coli was also investigated at 37°C and pH 5.5. The test results are shown in FIG. Figure 5 The test results show that the sterilization rates of CSAH-0 against Staphylococcus aureus and Escherichia coli are 80.7% and 73.6% respectively.

[0042] In summary, the present invention prepares a functional material doped with silver-modified calcium peroxide nanoparticles, wherein the functional material uses oxidized dextran and carboxymethyl chitosan as a skeleton structure to prepare a Schiff base hydrogel, and dopes the Schiff base hydrogel with silver-modified calcium peroxide nanoparticles; the silver-modified calcium peroxide nanoparticles are obtained by modifying the surface of calcium peroxide with silicon dioxide and then modifying the silver nanoparticles; the functional material doped with silver-modified calcium peroxide nanoparticles has excellent antibacterial activity and long-acting antibacterial ability, has long-acting and excellent bactericidal activity against typical Gram-positive bacteria and Gram-negative bacteria, and has good antibacterial application in the microenvironment of bacterial infection.

[0043] The embodiments are preferred implementations of the present invention, but the present invention is not limited to the above-mentioned implementations. Any obvious improvements, substitutions or modifications that can be made by those skilled in the art without departing from the essential content of the present invention belong to the protection scope of the present invention.

Claims

1. A functional material of silver-doped modified calcium peroxide nanoparticles, characterized in that: The functional material is doped with silver-modified calcium peroxide nanoparticles in the network structure of Schiff base hydrogel through non-covalent interaction; the skeleton structure of the Schiff base hydrogel is oxidized dextran and carboxymethyl chitosan; the silver-modified calcium peroxide nanoparticles are obtained by loading silver nanoparticles on core-shell type silica-modified calcium peroxide; in the core-shell type silica-modified calcium peroxide, calcium peroxide is used as the core and silica is used as the shell.

2. The method for preparing the functional material of silver-doped calcium peroxide nanoparticles according to claim 1, characterized in that: The preparation method comprises: (1) Preparation of silver-doped calcium peroxide nanoparticles: Calcium peroxide, ammonia water, tetraethyl orthosilicate and trimercaptopropyltrimethoxysilane are dispersed in ethanol, mixed evenly and reacted under stirring for 1, and centrifuged and dried after the reaction to obtain silica-modified calcium peroxide; Dispersing silica-modified calcium peroxide, silver ammonia solution, and oxidized dextran solution in deionized water in sequence and reacting them under stirring conditions for 2, centrifuging and drying after the reaction to obtain silver-doped calcium peroxide nanoparticles; (2) Preparation of functional materials of silver-doped calcium peroxide nanoparticles: The silver-doped calcium peroxide nanoparticles are dispersed in deionized water, and the oxidized dextran solution and carboxymethyl chitosan are added in sequence, and the mixture is rapidly stirred, poured into a mold, and allowed to stand to form a gel, thereby obtaining the functional material of the silver-doped calcium peroxide nanoparticles.

3. The method for preparing the functional material of silver-doped calcium peroxide nanoparticles according to claim 2, characterized in that: In step (1), the usage ratio of calcium peroxide, ammonia water, tetraethyl orthosilicate and trimercaptopropyltrimethoxysilane is 10-30 mg; 1-4 mL; 0.1-0.8 mL; 0.1-0.8 mL.

4. The method for preparing the functional material of silver-doped calcium peroxide nanoparticles according to claim 2, characterized in that: In step (1), the conditions of reaction 1 are: reacting at room temperature for 8-12 hours.

5. The method for preparing the functional material of silver-doped calcium peroxide nanoparticles according to claim 2, characterized in that: In step (1), the amount of silica-modified calcium peroxide, silver ammonia solution and oxidized dextran solution is 10-30 mg; 0.1-0.4 mL; 0.1-1 mL; wherein the concentration of the silver ammonia solution is 0.1-0.3 mol / L.

6. The method for preparing the functional material of silver-doped calcium peroxide nanoparticles according to claim 2, characterized in that: Step (1), the conditions of reaction 2 are: reacting at room temperature for 10-30 minutes.

7. The method for preparing the functional material of silver-doped calcium peroxide nanoparticles according to claim 2, characterized in that: In step (2), the amount of oxidized dextran solution and silver-doped modified calcium peroxide nanoparticles used is 5-15 mL; 10-30 mg.

8. The method for preparing the functional material of silver-doped calcium peroxide nanoparticles according to claim 2, characterized in that: In step (2), the amount of oxidized dextran solution and carboxymethyl chitosan used is 5-15 mL; 0.2-0.5 g.

9. Use of the functional material of silver-doped calcium peroxide nanoparticles modified according to claim 1 in antibacterial applications.

10. The use according to claim 9, characterized in that: The bacteria include Staphylococcus aureus and Escherichia coli.

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