antiviral agents

Abstract

To provide a novel antibacterial and antiviral agent.SOLUTION: An antibacterial and antiviral agent comprises a manganese compound.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to a novel antibacterial and antiviral agent. [Background technology]

[0002] Since the SARS (Severe Acute Respiratory Syndrome) outbreak in China in 2002, viral infections such as Ebola hemorrhagic fever and avian influenza have posed a threat around the world. With the recent COVID-19 outbreak now causing over 40,000 infections and over 1,000 deaths, there is growing interest in preventing viral infections. In addition, there are outbreaks of norovirus and influenza infections in facilities such as hospitals and nursing homes, as well as hospital-acquired infections caused by drug-resistant bacteria such as MRSA, and immediate countermeasures are needed.

[0003] To solve these problems, antiviral agents have been developed that use a catalyst in which gold nanoparticles are deposited on the surface of inorganic fine particles (Patent Document 1), and antiviral agents that use a palladium oxide catalyst (Patent Document 2). [Prior art documents] [Patent documents]

[0004] [Patent Document 1] Japanese Patent Application Laid-Open No. 2011-213719 [Patent Document 2] Japanese Patent Application Laid-Open No. 2012-020969 Summary of the Invention [Problem to be solved by the invention]

[0005] However, both Patent Documents 1 and 2 use precious metals, which has the disadvantage of increasing manufacturing costs.

[0006] An object of the present invention is to provide a novel antibacterial and antiviral agent. [Means for solving the problem]

[0007] The gist of the present invention is as follows. [1] An antibacterial and antiviral agent containing a manganese compound. [2] The antibacterial or antiviral agent according to claim 1, characterized in that the manganese compound contains at least one of potassium permanganate, manganese nitrate, and manganese dioxide. [Effects of the Invention]

[0008] According to the present invention, a novel antibacterial and antiviral agent can be provided. DETAILED DESCRIPTION OF THE INVENTION

[0009] One embodiment of the present invention will now be described in detail. The antibacterial and antiviral agent of this embodiment contains, as an active ingredient, a manganese compound, which is a compound containing manganese (Mn) as a constituent element. In this specification, the term "antibacterial and antiviral agent" refers to an agent used to inactivate fungi and / or viruses. Examples of fungi include bacteria, fungi, and both.

[0010] The mechanism by which the antibacterial and antiviral agent of this embodiment inactivates bacteria, fungi, and other microorganisms, as well as viruses, is not entirely clear at present, but it is speculated that the main cause is that the strong oxidizing action of manganese compounds causes oxidative damage to the lipid membranes and proteins of fungi and viruses. Examples of manganese compounds include permanganates and oxides. Examples of permanganates include potassium permanganate (KMnO4), NaMnO4, Zn(MnO4)2, Ca(MnO4)2, and Ba(MnO4)2. Examples of oxides include manganese dioxide (MnO2), Mn2O3, and Mn3O4. Among the oxides, MnO2 is particularly unique, as it has a unique crystal structure, resulting in α-manganese dioxide (α-MnO2; K + , Na + , Pb2+ , Ba 2+ Manganese dioxide may be of the following types: manganese dioxide (β-MnO), γ-manganese dioxide (γ-MnO), δ-manganese dioxide (δ-MnO), ε-manganese dioxide (ε-MnO), R-manganese dioxide (R-MnO), λ-manganese dioxide (λ-MnO), amorphous manganese dioxide, etc. The manganese compound may also be other compounds, such as manganese nitrate, manganese carbonate, manganese-containing ferrites (e.g., manganese ferrite MnFeO), manganese salts such as manganese dicarboxylates, manganese citrates, and fatty acid manganese salts, oxyhydroxides, and halides such as manganese chloride. The manganese compound according to this embodiment may also be a manganese compound supported by a metal such as gold, silver, zinc, or copper. The antibacterial and antiviral agent of this embodiment may contain two or more manganese compounds, for example, two or more of the above-mentioned manganese compounds. Among these, potassium permanganate, manganese nitrate, and manganese dioxide are preferred as the manganese compound for the antibacterial and antiviral agent of this embodiment because they have higher antibacterial and antiviral effects.

[0011] There are no particular limitations on the viruses that can be inactivated by the antibacterial and antiviral agent of this embodiment, and various viruses can be inactivated regardless of the type of genome or whether they have an envelope. Examples of viruses that can be inactivated include rhinovirus, poliovirus, foot-and-mouth disease virus, rotavirus, norovirus, enterovirus, hepatovirus, astrovirus, sapovirus, hepatitis E virus, influenza A, B, or C virus, parainfluenza virus, mumps virus, measles virus, human metapneumovirus, respiratory syncytial virus, Nipah virus, Hendra virus, yellow fever virus, dengue virus, Japanese encephalitis virus, West Nile virus, hepatitis B or C virus, eastern and western equine encephalitis virus, Onyong-nyong virus, rubella virus, Lassa virus, Junin virus, and machi virus. Examples of such viruses include rabies virus, rabies virus, rabies virus, rabies virus, rabies virus (serotype 1), rabies virus (serotype 2), rabies virus (serotype 3), rabies virus (serotype 4), rabies virus (serotype 5), rabies virus (serotype 6), rabies virus (serotype 7), rabies virus (serotype 8), rabies virus (serotype 9), rabies virus (serotype 10), rabies virus (serotype 11), rabies virus (serotype 12), rabies virus (serotype 13), rabies virus (serotype 14), rabies virus (serotype 15), rabies virus (serotype 16), rabies virus (serotype 17), rabies virus (serotype 18), rabies virus (serotype 19 ...

[0012] Furthermore, the type of bacteria that can be inactivated by the antibacterial and antiviral agent of this embodiment is not particularly limited. For example, various bacteria can be inactivated regardless of their properties, such as gram-positive, gram-negative, aerobic, or anaerobic. Examples of bacteria that can be inactivated include Escherichia coli, Staphylococcus aureus, Staphylococcus epidermidis, streptococci, Streptococcus pneumoniae, Haemophilus influenzae, Bordetella pertussis, Salmonella enteritidis, Klebsiella pneumoniae, Pseudomonas aeruginosa, Vibrio, Salmonella, Vibrio cholerae, Shigella, Bacillus anthrax, Mycobacterium tuberculosis, Clostridium botulinum, Clostridium tetani, and streptococci. Examples of fungi that can be inactivated by the antibacterial and antiviral agent of this embodiment include ringworm fungi such as Trichophyton rubrum, Trichophyton mentagrophytes, Trichophyton tonsurans, Microsporum canis, Microsporum gypseum, and Trichophyton verrucosum; aspergillus fungi such as Aspergillus niger, Aspergillus ochraceus, and Aspergillus oryzae; penicillium fungi belonging to the genera Eupenicillium, Hailer, Penicilliopsis, Talaromyces, and Trichocoma that grow on food; and Eurotium tonophilum, Penicillium citrinum, Penicillium pinophilum, Rhizopus oryzae, Cladosporium cladosporioides, Aureobasidium pullulans, Trichoderma virens, and Chaetomium, which are specified in the JIS antifungal test. globosum, Myrothecium verrucaria, etc., but are not limited to these.

[0013] The antibacterial and antiviral agent of this embodiment can be used in various forms. Furthermore, the antibacterial and antiviral agent of this embodiment may contain components other than the manganese compound as long as the object of the present invention can be achieved, and is not particularly limited. For example, from the viewpoint of handling, the antibacterial and antiviral agent of this embodiment is most preferably used in powder form, but is not limited thereto. For example, the agent may be used in a state dispersed in a dispersion medium such as water or alcohol, or the dispersion may be impregnated into a substrate such as a nonwoven fabric and used like a wet wipe. Here, when the antibacterial and antiviral agent of this embodiment is dispersed in a dispersion medium to form a dispersion, it is preferable that a dispersant be included to improve dispersion stability. As the dispersant, for example, a surfactant can be used, and specific examples include anionic surfactants, nonionic surfactants, and polymeric dispersants.

[0014] Anionic surfactants can have a carboxylic acid, sulfonic acid, or phosphoric acid structure as a hydrophilic group. Carboxylic acid surfactants include, for example, fatty acid salts and cholate salts, which are the main components of soap. Sulfonic acid surfactants include linear alkylbenzenesulfonate and sodium lauryl sulfate, which are commonly used in synthetic detergents. More specifically, examples include fatty acid soda soap, potassium oleate soap, and carboxylates such as alkyl ether carboxylates; sulfates such as sodium lauryl sulfate, higher alcohol sodium sulfate, triethanolamine lauryl sulfate, sodium polyoxyethylene lauryl ether sulfate, and sodium polyoxyethylene alkyl ether sulfate; sulfonates such as sodium dodecylbenzenesulfonate, sodium alkylnaphthalenesulfonate, sodium alkyldiphenyletherdisulfonate, sodium alkanesulfonate, and sodium salts of aromatic sulfonic acid-formalin condensates; potassium alkylphosphates, sodium hexametaphosphate, and dialkylsulfosuccinates. These surfactants can be used alone or in combination.

[0015] Examples of nonionic surfactants include alkylphenol ethylene oxide adducts and higher alcohol ethylene oxide adducts, polyoxyethylene fatty acid esters, fatty acid ethylene oxide adducts and polyethylene glycol fatty acid esters, higher alkylamine ethylene oxide adducts and fatty acid amide ethylene oxide adducts, polyoxyethylene alkylamines and polyoxyethylene fatty acid amides, polypropylene glycol ethylene oxide adducts, nonionic surfactants, fatty acid esters of glycerin and pentaerythritol, fatty acid esters of sorbitol and sorbitan, fatty acid esters of sucrose, alkyl polyglycoside fatty acids, alkanolamides, etc. These may be used alone or in combination.

[0016] Further, examples of polymeric dispersants include polyurethane prepolymers, styrene-polycarboxylic acid copolymers, lignin sulfonates, carboxymethyl cellulose, acrylates, polystyrene sulfonates, acrylamides, polyvinylpyrrolidone, casein, and gelatin, and examples of oligomers and prepolymers include unsaturated polyesters, unsaturated acrylics, epoxy acrylates, urethane acrylates, polyester acrylates, polyether acrylates, polybutadiene acrylates, silicone acrylates, maleimides, polyene / polythiols, and alkoxy oligomers. These may be used alone or in combination.

[0017] Furthermore, when the antibacterial and antiviral agent of the present embodiment is used as a dispersion, it may be mixed with a known antiviral agent, antibacterial agent, antifungal agent, antiallergen agent, catalyst, antireflective material, material having heat-shielding properties, or the like.

[0018] When the manganese compound of the antibacterial and antiviral agent of this embodiment is in particulate form, such as a powder or dispersed in a dispersion medium, its size can be appropriately determined depending on the intended use. For example, in honeycomb filters, a powdered manganese compound with an average particle size of 0.1 μm to 1,000 μm can be molded by pressure molding or calcination with an inorganic binder. Furthermore, when the compound is fixed to a fiber structure such as a woven fabric or nonwoven fabric, when filled in a polymeric material, or when fixed to a filter such as a honeycomb, the average particle size is preferably 100 μm or less, more preferably 100 nm or less, and even more preferably 10 nm or less. From the perspectives of particle manufacturing, handleability, and chemical stability, a particle size of 1 nm or more is preferred. In this specification, the average particle size refers to the volume-average particle size (D50) at which the cumulative volume reaches 50% in a volume-based particle size distribution measured by laser diffraction or the like.

[0019] Furthermore, the manganese compound of the antibacterial and antiviral agent of this embodiment may be dissolved in a solvent, depending on the type of compound. Examples of the solvent include amphipathic solvents such as water, alcohols such as methanol and ethanol, acetone, and mixtures thereof, depending on the compound. The amount of manganese compound dissolved is not particularly limited, as long as the required amount (an amount sufficient to exert antibacterial and antiviral effects) is dissolved in the solvent. Adjusting the pH of the solvent to a neutral to slightly acidic range is preferable, as it enhances the oxidizing effect of the manganese compound and allows various fungi and viruses to be inactivated in a shorter time.

[0020] The antibacterial and antiviral agent of the present embodiment may be used alone, or may be formed into a structure such as a fiber structure comprising the antibacterial and antiviral agent of the present embodiment, and is not particularly limited. Specifically, the fiber structure may have a structure in which the antibacterial and antiviral agent of this embodiment is contained in the fiber structure or fixed to the outer surface of the fiber structure.

[0021] The method of inclusion or fixation can be appropriately selected by those skilled in the art and is not particularly limited. For example, the antibacterial and antiviral agent may be kneaded and spun into a polymeric material to produce a woven fabric, knitted fabric, nonwoven fabric, or the like. It may also be kneaded into pulp or the like to produce paper. It may also be fixed to a fiber structure such as a woven fabric or nonwoven fabric via a binder or the like, or it may be mixed and fixed together with an adhesive or the like during the production of fleece or mixed paper. In this specification, the inclusion of an antibacterial and antiviral agent is a concept that also includes cases where the antibacterial and antiviral agent is exposed to the outer surface.

[0022] Specific examples of the fiber structures include masks, air conditioner filters, air purifier filters, vacuum cleaner filters, ventilation fan filters, vehicle filters, air conditioner filters, deodorizer filters, various exhaust gas filters, clothing, protective clothing, bedding, screen nets for door doors, and nets for livestock farming sites such as chicken coops and pig sties. These fiber structures are made of polymer materials such as polyester, polyethylene, polypropylene, polyvinyl chloride, polyethylene terephthalate, polybutylene terephthalate, polytetramethylene terephthalate, nylon, acrylic, polytetrafluoroethylene, polyvinyl alcohol, Kevlar, polyacrylic acid, polymethyl methacrylate, rayon, cupra, Tencel, Polynosic, acetate, triacetate, cellulose, cotton, hemp, wool, silk, and bamboo; inorganic fibers such as glass fiber, carbon fiber, ceramic fiber, calcium silicate fiber, and alkaline earth silicate wool; and fibers containing metals such as aluminum, iron, stainless steel, brass, copper, tungsten, and titanium.

[0023] The fixing method can be appropriately selected by a person skilled in the art and is not particularly limited. For example, the antibacterial and antiviral agent of the present embodiment may be fixed to a fiber structure such as a woven fabric or nonwoven fabric using a binder or a coupling agent, or the antibacterial and antiviral agent of the present embodiment may be fixed to the fiber structure by fixing an inorganic material carrying the agent to the fiber structure. Alternatively, the antibacterial and antiviral agent may be fixed by impregnating the fiber structure with an aqueous solution in which a manganese compound is dissolved.

[0024] The binder component is not particularly limited, but examples of suitable synthetic resins include polyester resin, amino resin, epoxy resin, polyurethane resin, acrylic resin, water-soluble resin, vinyl resin, fluororesin, silicone resin, cellulose resin, phenol resin, xylene resin, and toluene resin, and examples of suitable natural resins include drying oils such as castor oil, linseed oil, and tung oil. Silane monomers or the like having unsaturated bonds may be chemically bonded by refluxing or the like, dispersed in a solvent such as methanol, applied to or immersed in a fiber base, and then irradiated with radiation such as an electron beam to chemically bond the resulting material by graft polymerization. Further, examples of inorganic materials include aluminum oxide, titanium oxide, zirconium oxide, silicon dioxide, etc. Furthermore, alkoxysilanes may be hydrolyzed and used.

[0025] Furthermore, the antibacterial and antiviral agent of this embodiment can also be structured so as to be contained in a molded body or fixed to the outside of a molded body. As with the fiber structure, there are no particular limitations on the method for containing or fixing to the outside. In this specification, the molded body is a concept that also includes films and sheets. It can also be mixed with paint and applied to the surface of a target component. Furthermore, the molded body is not limited to organic materials, and includes those made of inorganic materials such as ceramic honeycomb.

[0026] Specifically, the molded article may be directly applied to molded filters such as air conditioner filters and air purifier filters, wallpaper, windows, ceilings, vehicle seats, doors, blinds, chairs, sofas, flooring materials, interior materials for equipment that handles bacteria and viruses, trains and cars, interior materials for buildings such as hospitals, agricultural materials, and sheet shutters, as well as panels, building materials, interior materials, writing implements, handrails, straps, telephones, toys, and doorknobs to form a film (coating film). Specific examples of structures that include (for example, contain or are externally fixed to) the antibacterial and antiviral agent of this embodiment include air purification filters. Examples of air purification filters include fiber structures and molded articles, and more specific examples include air conditioner filters, air purifier filters, vacuum cleaner filters, ventilation fan filters, vehicle filters, air conditioner filters, deodorizer filters, and various exhaust gas filters.

[0027] As described above in detail, the antibacterial and antiviral agent of this embodiment can be a useful material that can provide a variety of excellent products in a variety of fields. [Example]

[0028] Next, the present invention will be described in more detail with reference to examples, although the present invention is not limited to these examples.

[0029] [Creation of antibacterial and antiviral agents] Example 1 Potassium permanganate used was manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.

[0030] Example 2 Manganese (II) nitrate hexahydrate was used, manufactured by Sigma-Aldrich Japan.

[0031] Example 3 0.525 g of MnSO4·H2O was dissolved in 20 mL of pure water. 1.25 g of KMnO4 was dissolved in 40 mL of pure water. The KMnO4 aqueous solution was added to the MnSO4·H2O aqueous solution and stirred at room temperature for 30 minutes, after which hydrothermal synthesis was carried out at 160°C for 12 hours. The mixture was then filtered and washed, and dried at 80°C for 8 hours to obtain α-type manganese dioxide.

[0032] Example 4 0.525 g of MnSO4·H2O was dissolved in 20 mL of pure water. 1.25 g of KMnO4 was dissolved in 40 mL of pure water. The KMnO4 aqueous solution was added to the MnSO4·H2O aqueous solution and stirred at room temperature for 30 minutes. After filtration and washing, the mixture was dried at 150°C to obtain amorphous manganese dioxide.

[0033] Example 5 8.8 g of MnSO4·H2O was dissolved in 30 mL of pure water, and then 3 mL of concentrated nitric acid was added to dissolve the mixture. 5.89 g of KMnO4 was dissolved in 100 mL of pure water. The KMnO4 aqueous solution was added to the MnSO4·H2O aqueous solution, and the mixture was refluxed at 100°C for 24 hours. After filtration and washing, the mixture was dried at 120°C to obtain α-type manganese dioxide.

[0034] Example 6 2.484 g of MnSO4·H2O and 1.659 g of KMnO4 were dissolved in 75 mL of pure water and subjected to hydrothermal synthesis at 160°C for 24 hours. The solution was then filtered, washed, and dried at 120°C for 24 hours. It was then calcined at 500°C for 6 hours to obtain hollandite-type manganese dioxide. 2 g of the resulting hollandite-type manganese dioxide was suspended in 100 mL of pure water, and 20 mL of Ag(NH3)2OH solution and 30 mL of 30 wt% H2O2 solution were added and stirred for 3 hours. The solution was then filtered, washed, dried at 80°C for 24 hours, and calcined at 400°C for 6 hours to obtain Ag-loaded manganese dioxide.

[0035] Example 7 As an example of amorphous manganese dioxide different from that used in Example 4, Nippon Denko Corporation's CMD-K200 was used.

[0036] Example 8 As an example of ε-type manganese dioxide, AMD250 manufactured by Japan Metals and Chemical Industries, Ltd. was used.

[0037] Example 9 As an example of α-type manganese dioxide different from that used in Examples 3 and 5, LMD180 manufactured by Japan Metals and Chemical Industries, Ltd. was used.

[0038] (Control (Comparative Example 1)) A PBS solution containing no substance of the Examples was used as a control.

[0039] [Sterilization test method] 25 μL of each substance in the Examples, adjusted to 200 mg / mL, was mixed with 25 μL of Escherichia coli bacterial suspension to prepare test samples. Each sample was stirred using a microtube mixer and reacted at room temperature for 60 minutes. After 60 minutes of stirring, 20 μL of each sample was removed and added to 3.98 mL of SCDLP medium to terminate the reaction between the bacteria and each substance. Each sample was then serially diluted 10 times with SCDLP medium, and 1 mL of the diluted solution was placed in a Petri dish, mixed with dissolved NB agar medium, and cultured at 37°C. The number of colonies formed (CFU / 1 mL, Log10) (CFU: colony-forming unit) was calculated to evaluate the bactericidal activity of each substance against bacteria.

[0040] [Antiviral evaluation] 100 μL of each substance from the Examples, adjusted to 200 mg / mL and 10 mg / mL, was mixed with 100 μL of each influenza virus suspension to prepare test samples. Each sample was incubated at room temperature for 60 minutes while stirring using a microtube mixer. After 60 minutes of stirring, 800 μL of SCDLP medium was added to terminate the reaction between the virus and each substance. Each sample was then serially diluted 10 times using MEM medium. 100 μL of the diluted solution was inoculated onto MDCK cells cultured in a 6-well plate. After allowing the cells to stand for 60 minutes to allow the virus to adsorb to the cells, MEM agar medium was overlaid and the cells were incubated for 48 hours at 34°C in a 5% CO2 incubator. After 48 hours, the cells were fixed with formalin and stained with methylene blue. The number of plaques formed was counted, and the virus infectivity titer (PFU: plaque-forming units) was calculated to evaluate the antiviral activity of each substance against the virus.

[0041] [Table 1]

[0042] From the above results, it was confirmed that all Examples had higher antibacterial and antiviral effects than Comparative Example 1. By applying these antibacterial and antiviral agents, useful antibacterial and antiviral members can be provided.

Claims

1. An antiviral agent for influenza virus containing manganese dioxide as an active ingredient.

2. 2. The antiviral agent for influenza virus according to claim 1, wherein the manganese dioxide is α-type or ε-type.

3. 3. The antiviral agent for influenza virus according to claim 1, comprising manganese dioxide particles.

4. 4. The antiviral agent for influenza virus according to claim 3, wherein the manganese dioxide particles have an average particle size of 1 nm or more and 100 μm or less.

5. 5. The antiviral agent for influenza virus according to claim 3, further comprising a dispersion medium, wherein the manganese dioxide particles are dispersed in the dispersion medium.

6. A fiber structure containing the antiviral agent for influenza virus according to any one of claims 1 to 4 or having the agent fixed to its outer surface.

7. A molded article containing the antiviral agent for influenza virus according to any one of claims 1 to 4 or having the agent fixed to its outer surface.

8. A paint containing the antiviral agent for influenza virus according to any one of claims 1 to 4.

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