A quaternary ammonium salt composite antibacterial agent and preparation method thereof

Abstract

The invention discloses a quaternary ammonium salt composite antibacterial agent and a preparation method thereof. The method comprises the following steps: step S1, preparing zinc oxide nanoparticles; step S2, adding the prepared zinc oxide nanoparticles into a buffer solution, adding dopamine hydrochloride, and reacting to obtain modified zinc oxide; step S3, adding the modified zinc oxide and 1-vinyl imidazole into N,N-dimethylformamide, reacting for 2-2.5 hours, and obtaining modified zinc oxide; and step S4, adding the modified zinc oxide and 1-bromopentane into cyclohexane under a nitrogen atmosphere, heating the mixture to 50 DEG C, and obtaining the quaternary ammonium salt composite antibacterial agent. The antibacterial effect of the antibacterial agent is significantly improved by the synergistic effect of the zinc oxide nanoparticles by the quaternary ammonium salt, and the antibacterial effect of the composite antibacterial agent is significantly improved by the insertion of imidazole quaternary ammonium salt into the surface of the zinc oxide, and the synergistic antibacterial property of the quaternary ammonium salt and the zinc oxide, and the introduced imidazole group can significantly improve the thermal stability of the composite antibacterial agent.

Description

Technical Field

[0001] The present invention relates to the technical field of antimicrobial agents, and in particular to a quaternary ammonium salt composite antimicrobial agent and a preparation method thereof. Background Art

[0002] In daily life, various surfaces are susceptible to invasion by microorganisms (bacteria, viruses, etc.) in the air and solutions, which may endanger human health. Potentially harmful bacteria are everywhere around us. For example, talking, coughing, sneezing, and even breathing will produce water vapor droplets containing bacteria. Similarly, bacteria present in liquids (for example, drinking water and hospital catheter fluids) can attach to the inner surface of blood vessels and pipes and grow and multiply. When the number of cells increases on the surface, microbial cells usually begin to form a biofilm, which is composed of a polysaccharide matrix in which the cells are embedded. This biofilm allows microbial cells to survive in harsh conditions, and the embedded cells can reduce their sensitivity to most antibiotics and other biocides by up to 1,000 times, which can become a source of stubborn infections.

[0003] Quaternary ammonium salt antimicrobial agent is a broad-spectrum antimicrobial agent that can effectively kill bacteria, molds, yeasts and other microorganisms. It also has a good inhibitory effect on intestinal pathogens and bacteria contaminating food. It is highly efficient and can kill or inhibit microorganisms in a relatively short period of time, effectively preventing food spoilage, bacterial infection and other problems. However, quaternary ammonium salts have poor thermal stability. Therefore, how to improve the heat resistance of quaternary ammonium salt antimicrobial agents and further improve the antibacterial effect is a technical problem that needs to be solved urgently. Summary of the Invention

[0004] In order to solve the above technical problems, the present invention provides a quaternary ammonium salt composite antibacterial agent and a preparation method thereof.

[0005] The purpose of the present invention can be achieved through the following technical solutions:

[0006] A method for preparing a quaternary ammonium salt composite antibacterial agent comprises the following steps:

[0007] Step S1, zinc acetate dihydrate and tetrabutylammonium bromide are added to anhydrous ethanol, the temperature is raised and refluxed to react for 1 hour, and after the reaction is completed, a 10% by mass potassium hydroxide ethanol solution is added, stirring is continued and the reaction is continued for 12 hours. After the reaction is completed, centrifugation and precipitation are performed, and the mixture is washed three times with methanol to obtain zinc oxide nanoparticles. The dosage ratio of zinc acetate dihydrate, tetrabutylammonium bromide, potassium hydroxide and anhydrous ethanol is controlled to be 4.10-4.20 g: 6.0-6.05 g: 0.8-1 g: 20-30 mL.

[0008] Step S2, adding the prepared zinc oxide nanoparticles to a Tris-buffer buffer solution with a pH of 8.5, stirring at a constant speed, and adding dopamine hydrochloride, stirring at a constant speed and reacting at room temperature for 2 hours, centrifuging after the reaction, and washing the filter cake three times with deionized water to obtain modified zinc oxide, wherein the amount ratio of zinc oxide nanoparticles, Tris-buffer buffer solution, and dopamine hydrochloride is controlled to be 2-5 g:100-150 mL:0.2-0.5 g;

[0009] In step S2, dopamine hydrochloride is polymerized on the surface of zinc oxide nanoparticles to form polydopamine, thereby preparing modified zinc oxide.

[0010] Step S3, adding modified zinc oxide and 1-vinylimidazole to N,N-dimethylformamide, stirring at a uniform speed and adding 1,8-diazabicycloundec-7-ene, continuing stirring and reacting for 2-2.5 hours to obtain modified zinc oxide, wherein the amount ratio of modified zinc oxide, 1-vinylimidazole and N,N-dimethylformamide is controlled to be 2-2.5 g:1-1.2 g:100 mL, and the amount of 1,8-diazabicycloundec-7-ene is 3-5% of the total weight of the modified zinc oxide and 1-vinylimidazole;

[0011] In step S3, the amino group on the modified zinc oxide and the carbon-carbon double bond on 1-vinylimidazole undergo Michael addition reaction, thereby grafting 1-vinylimidazole onto the surface of the zinc oxide.

[0012] Step S4: Under a nitrogen atmosphere, add the modified zinc oxide and 1-bromopentane to cyclohexane, heat to 50° C., stir uniformly and react for 24 hours, filter and wash to obtain a quaternary ammonium salt composite antibacterial agent, and control the amount ratio of the modified zinc oxide, 1-bromopentane and cyclohexane to be 1-1.8 g: 2.25-2.45 g: 10-20 mL.

[0013] In step S4, the imidazole group on the modified zinc oxide undergoes a quaternization reaction with 1-bromopentane, and imidazole quaternary ammonium salt is introduced into the surface of the zinc oxide. The antibacterial effect of the composite antibacterial agent is significantly improved through the synergistic antibacterial property of the quaternary ammonium salt and zinc oxide, and the introduced imidazole group can significantly improve the thermal stability of the composite antibacterial agent.

[0014] A quaternary ammonium salt composite antibacterial agent is prepared by the above preparation method.

[0015] The invention has the beneficial effects of preparing a quaternary ammonium salt composite antibacterial agent, which significantly improves the antibacterial effect of the antibacterial agent by synergizing zinc oxide nanoparticles with the quaternary ammonium salt. During the preparation process of the antibacterial agent, dopamine hydrochloride is first polymerized on the surface of the zinc oxide nanoparticles to form polydopamine to prepare modified zinc oxide, then an amino group on the modified zinc oxide and a carbon-carbon double bond on 1-vinylimidazole undergo Michael addition reaction, and then 1-vinylimidazole is grafted onto the surface of the zinc oxide, and finally an imidazole group on the modified zinc oxide undergoes a quaternization reaction with 1-bromopentane, and an imidazole quaternary ammonium salt is grafted onto the surface of the zinc oxide. The antibacterial effect of the composite antibacterial agent is significantly improved by the synergistic antibacterial property of the quaternary ammonium salt and the zinc oxide, and the introduced imidazole group can significantly improve the thermal stability of the composite antibacterial agent. DETAILED DESCRIPTION

[0016] The following is a clear and complete description of the technical solutions in the embodiments of the present invention. Obviously, the embodiments described are only some embodiments of the present invention, not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making any creative efforts are within the scope of protection of the present invention.

[0017] Example 1: A method for preparing a quaternary ammonium salt composite antibacterial agent, comprising the following steps:

[0018] Step S1, zinc acetate dihydrate and tetrabutylammonium bromide are added to anhydrous ethanol, the temperature is raised and refluxed to react for 1 hour, and after the reaction is completed, a 10% by mass potassium hydroxide ethanol solution is added, stirring is continued and the reaction is continued for 12 hours. After the reaction is completed, centrifugation and precipitation are performed, and the mixture is washed three times with methanol to obtain zinc oxide nanoparticles. The amount ratio of zinc acetate dihydrate, tetrabutylammonium bromide, potassium hydroxide and anhydrous ethanol is controlled to be 4.10g:6.0g:0.8g:20mL.

[0019] Step S2, adding the prepared zinc oxide nanoparticles to a Tris-buffer buffer solution with a pH of 8.5, stirring at a constant speed, and adding dopamine hydrochloride, stirring at a constant speed and reacting at room temperature for 2 hours, centrifuging after the reaction, and washing the filter cake three times with deionized water to obtain modified zinc oxide, wherein the amount ratio of zinc oxide nanoparticles, Tris-buffer buffer solution, and dopamine hydrochloride is controlled to be 2g:100mL:0.2g;

[0020] Step S3, adding the modified zinc oxide and 1-vinylimidazole to N,N-dimethylformamide, stirring at a uniform speed and adding 1,8-diazabicycloundec-7-ene, continuing stirring and reacting for 2-2.5 hours to obtain modified zinc oxide, wherein the amount ratio of the modified zinc oxide, 1-vinylimidazole and N,N-dimethylformamide is controlled to be 2g:1g:100mL, and the amount of 1,8-diazabicycloundec-7-ene is 3% of the total weight of the modified zinc oxide and 1-vinylimidazole;

[0021] Step S4: Under a nitrogen atmosphere, the modified zinc oxide and 1-bromopentane were added to cyclohexane, the temperature was raised to 50° C., the mixture was stirred at a uniform speed and reacted for 24 hours, filtered, and washed to obtain a quaternary ammonium salt composite antibacterial agent, and the amount ratio of the modified zinc oxide, 1-bromopentane, and cyclohexane was controlled to be 1 g:2.25 g:10 mL.

[0022] After 14 days of high temperature testing at 54°C, the effective content decreased by less than 5%.

[0023] After 90 days of high temperature testing at 37°C, the effective content decreased by less than 10%.

[0024] Example 2: A method for preparing a quaternary ammonium salt composite antibacterial agent, comprising the following steps:

[0025] Step S1, zinc acetate dihydrate and tetrabutylammonium bromide are added to anhydrous ethanol, the temperature is raised and refluxed to react for 1 hour, and after the reaction is completed, a 10% by mass potassium hydroxide ethanol solution is added, stirring is continued and the reaction is continued for 12 hours. After the reaction is completed, centrifugation and precipitation are performed, and the mixture is washed three times with methanol to obtain zinc oxide nanoparticles. The amount ratio of zinc acetate dihydrate, tetrabutylammonium bromide, potassium hydroxide and anhydrous ethanol is controlled to be 4.12g:6.02g:0.8g:25mL.

[0026] Step S2, adding the prepared zinc oxide nanoparticles to a Tris-buffer buffer solution with a pH of 8.5, stirring at a constant speed, and adding dopamine hydrochloride, stirring at a constant speed and reacting at room temperature for 2 hours, centrifuging after the reaction, and washing the filter cake three times with deionized water to obtain modified zinc oxide, wherein the amount ratio of zinc oxide nanoparticles, Tris-buffer buffer solution, and dopamine hydrochloride is controlled to be 3 g:120 mL:0.3 g;

[0027] Step S3, adding the modified zinc oxide and 1-vinylimidazole to N,N-dimethylformamide, stirring at a uniform speed and adding 1,8-diazabicycloundec-7-ene, continuing stirring and reacting for 2.2 hours to obtain modified zinc oxide, wherein the amount ratio of the modified zinc oxide, 1-vinylimidazole and N,N-dimethylformamide is controlled to be 2.2 g:1.1 g:100 mL, and the amount of 1,8-diazabicycloundec-7-ene is 4% of the total weight of the modified zinc oxide and 1-vinylimidazole;

[0028] Step S4: Under a nitrogen atmosphere, the modified zinc oxide and 1-bromopentane were added to cyclohexane, the temperature was raised to 50° C., the mixture was stirred at a uniform speed and reacted for 24 hours, filtered, and washed to obtain a quaternary ammonium salt composite antibacterial agent, and the amount ratio of the modified zinc oxide, 1-bromopentane, and cyclohexane was controlled to be 1.7 g:2.30 g:15 mL.

[0029] After 14 days of high temperature testing at 54°C, the effective content decreased by less than 5%.

[0030] After 90 days of high temperature testing at 37°C, the effective content decreased by less than 10%.

[0031] Example 3: A method for preparing a quaternary ammonium salt composite antibacterial agent, comprising the following steps:

[0032] Step S1, zinc acetate dihydrate and tetrabutylammonium bromide are added to anhydrous ethanol, the temperature is raised and refluxed to react for 1 hour, and after the reaction is completed, a 10% by mass potassium hydroxide ethanol solution is added, stirring is continued and the reaction is continued for 12 hours. After the reaction is completed, centrifugation and precipitation are performed, and the mixture is washed three times with methanol to obtain zinc oxide nanoparticles. The amount ratio of zinc acetate dihydrate, tetrabutylammonium bromide, potassium hydroxide and anhydrous ethanol is controlled to be 4.18 g:6.04 g:1 g:30 mL.

[0033] Step S2, adding the prepared zinc oxide nanoparticles to a Tris-buffer buffer solution with a pH of 8.5, stirring at a constant speed, and adding dopamine hydrochloride, stirring at a constant speed and reacting at room temperature for 2 hours, centrifuging after the reaction, and washing the filter cake three times with deionized water to obtain modified zinc oxide, wherein the amount ratio of zinc oxide nanoparticles, Tris-buffer buffer solution, and dopamine hydrochloride is controlled to be 4g:150mL:0.4g;

[0034] Step S3, adding the modified zinc oxide and 1-vinylimidazole to N,N-dimethylformamide, stirring at a uniform speed and adding 1,8-diazabicycloundec-7-ene, continuing stirring and reacting for 2.4 hours to obtain modified zinc oxide, wherein the amount ratio of the modified zinc oxide, 1-vinylimidazole and N,N-dimethylformamide is controlled to be 2.4 g:1.2 g:100 mL, and the amount of 1,8-diazabicycloundec-7-ene is 5% of the total weight of the modified zinc oxide and 1-vinylimidazole;

[0035] Step S4: Under a nitrogen atmosphere, the modified zinc oxide and 1-bromopentane were added to cyclohexane, the temperature was raised to 50° C., the mixture was stirred at a uniform speed and reacted for 24 hours, filtered, and washed to obtain a quaternary ammonium salt composite antibacterial agent, and the amount ratio of the modified zinc oxide, 1-bromopentane, and cyclohexane was controlled to be 1.6 g:2.45 g:20 mL.

[0036] After 14 days of high temperature testing at 54°C, the effective content decreased by less than 5%.

[0037] After 90 days of high temperature testing at 37°C, the effective content decreased by less than 10%.

[0038] Example 4: A method for preparing a quaternary ammonium salt composite antibacterial agent, comprising the following steps:

[0039] Step S1, zinc acetate dihydrate and tetrabutylammonium bromide are added to anhydrous ethanol, the temperature is raised and refluxed for reaction for 1 hour, and after the reaction, a 10% by mass potassium hydroxide ethanol solution is added, stirring is continued and the reaction is continued for 12 hours. After the reaction is completed, centrifugation and precipitation are performed, and the mixture is washed three times with methanol to obtain zinc oxide nanoparticles. The amount ratio of zinc acetate dihydrate, tetrabutylammonium bromide, potassium hydroxide and anhydrous ethanol is controlled to be 4.20g:6.05g:1g:30mL.

[0040] Step S2, adding the prepared zinc oxide nanoparticles to a Tris-buffer buffer solution with a pH of 8.5, stirring at a constant speed, and adding dopamine hydrochloride, stirring at a constant speed and reacting at room temperature for 2 hours, centrifuging after the reaction, and washing the filter cake three times with deionized water to obtain modified zinc oxide, wherein the amount ratio of zinc oxide nanoparticles, Tris-buffer buffer solution, and dopamine hydrochloride is controlled to be 5g:150mL:0.5g;

[0041] Step S3, adding the modified zinc oxide and 1-vinylimidazole to N,N-dimethylformamide, stirring at a uniform speed and adding 1,8-diazabicycloundec-7-ene, continuing stirring and reacting for 2.5 hours to obtain modified zinc oxide, wherein the amount ratio of the modified zinc oxide, 1-vinylimidazole and N,N-dimethylformamide is controlled to be 2.5 g:1.2 g:100 mL, and the amount of 1,8-diazabicycloundec-7-ene is 5% of the total weight of the modified zinc oxide and 1-vinylimidazole;

[0042] Step S4: Under a nitrogen atmosphere, the modified zinc oxide and 1-bromopentane were added to cyclohexane, the temperature was raised to 50° C., the mixture was stirred at a uniform speed and reacted for 24 hours, filtered, and washed to obtain a quaternary ammonium salt composite antibacterial agent, and the amount ratio of the modified zinc oxide, 1-bromopentane, and cyclohexane was controlled to be 1.8 g:2.45 g:20 mL.

[0043] After 14 days of high temperature testing at 54°C, the effective content decreased by less than 5%.

[0044] After 90 days of high temperature testing at 37°C, the effective content decreased by less than 10%.

[0045] Comparative Example 1: Compared with Example 1, this comparative example uses nano zinc oxide instead of the composite antibacterial agent, and the rest is the same as Example 1.

[0046] Comparative Example 2: Compared with Example 1, this comparative example uses a commercially available quaternary ammonium salt instead of the composite antibacterial agent, and the rest is the same as Example 1.

[0047] The antibacterial properties of the antibacterial agents prepared in Examples 1-4 and Comparative Examples 1-2 were tested, and the results are shown in Table 1 below:

[0048] According to "Technical Specifications for Disinfection" (2002 edition) "2.1 Technical Specifications for Testing the Disinfection Effect of Disinfection Products", the prepared fungicide was tested for its bacterial and fungal killing rate at a concentration of 0.1% for 30 seconds; the prepared fungicide was tested for its virus killing rate at a concentration of 0.1% for 5 minutes.

[0049] Inspection basis:

[0050] Technical Specifications for Disinfection (2002 Edition) 2.1.1.5 Neutralizer Identification Test

[0051] Technical Specifications for Disinfection (2002 Edition) 2.1.1.7 Quantitative Bacterial Killing Test

[0052] Evaluation basis:

[0053] Technical Specifications for Disinfection (2002 Edition) 2.1.1.5 Neutralizer Identification Test

[0054] Technical Specifications for Disinfection (2002 Edition) 2.1.1.7 Quantitative Bacterial Killing Test

[0055] Table 1

[0056]

[0057] It can be seen from Table 1 above that the composite antibacterial agents prepared in Examples 1-4 of the present invention have excellent antibacterial properties.

[0058] The above content is merely an example and explanation of the concept of the present invention. Those skilled in the art may make various modifications or additions to the described specific embodiments or replace them in a similar manner. As long as they do not deviate from the concept of the invention or exceed the scope defined by the claims, they should all fall within the scope of protection of the present invention.

Claims

1. A method for preparing a quaternary ammonium salt composite antibacterial agent, characterized in that: The steps include: Step S1, adding zinc acetate dihydrate and tetrabutylammonium bromide to anhydrous ethanol, heating and refluxing for 1 hour, adding a 10% by mass potassium hydroxide ethanol solution after the reaction, continuing stirring and reacting for 12 hours, centrifuging and precipitating after the reaction, and washing three times with methanol to obtain zinc oxide nanoparticles; Step S2, adding the prepared zinc oxide nanoparticles to a Tris-buffer buffer solution with a pH of 8.5, stirring at a constant speed, adding dopamine hydrochloride, stirring at a constant speed and reacting at room temperature for 2 hours, centrifuging after the reaction, and washing the filter cake three times with deionized water to obtain modified zinc oxide; Step S3, adding the modified zinc oxide and 1-vinylimidazole to N,N-dimethylformamide, stirring at a uniform speed, adding 1,8-diazabicycloundec-7-ene, continuing stirring and reacting for 2-2.5 hours to obtain modified zinc oxide; Step S4: Under a nitrogen atmosphere, the modified zinc oxide and 1-bromopentane were added to cyclohexane, the temperature was raised to 50° C., the mixture was stirred at a constant speed and reacted for 24 hours, and the mixture was filtered and washed to obtain a quaternary ammonium salt composite antibacterial agent.

2. The method for preparing a quaternary ammonium salt composite antibacterial agent according to claim 1, wherein In step S1, the dosage ratio of zinc acetate dihydrate, tetrabutylammonium bromide, potassium hydroxide and anhydrous ethanol is controlled to be 4.10-4.20 g: 6.0-6.05 g: 0.8-1 g: 20-30 mL.

3. The preparation method of a quaternary ammonium salt composite antibacterial agent according to claim 1, wherein In step S2, the dosage ratio of zinc oxide nanoparticles, Tris-buffer buffer and dopamine hydrochloride is controlled to be 2-5 g:100-150 mL:0.2-0.5 g.

4. The preparation method of a quaternary ammonium salt composite antibacterial agent according to claim 1, wherein In step S3, the amount ratio of modified zinc oxide, 1-vinylimidazole and N,N-dimethylformamide is controlled to be 2-2.5 g:1-1.2 g:100 mL, and the amount of 1,8-diazabicycloundec-7-ene is 3-5% of the total weight of modified zinc oxide and 1-vinylimidazole.

5. The preparation method of a quaternary ammonium salt composite antibacterial agent according to claim 1, wherein In step S4, the dosage ratio of modified zinc oxide, 1-bromopentane and cyclohexane is controlled to be 1-1.8 g: 2.25-2.45 g: 10-20 mL.

6. A quaternary ammonium salt composite antibacterial agent, characterized in that: Prepared by the preparation method according to any one of claims 1 to 5.

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