Antiviral agent

Abstract

To provide an antiviral agent which demonstrates antimicrobial action against microorganisms including bacteria and fungi as well as an effect of suppressing viruses.SOLUTION: An antiviral agent contains, as active ingredients, (A) diiodomethyl-p-tolylsulfone and (B) zinc oxide.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to antiviral agents, antiviral products, methods for inhibiting viruses in non-human subjects, and methods for producing antivirally treated articles. [Background technology]

[0002] The spread of viral infections such as influenza and norovirus has occurred repeatedly in the past, and since infection with these viruses can cause severe symptoms such as high fever, severe vomiting, and diarrhea, consumers are very conscious of infection prevention. Therefore, there is a growing demand for not only antimicrobial properties (antibacterial, antifungal, antialgae, etc.) but also antiviral properties to be imparted to everyday items used by consumers. However, from a microbiological perspective, antimicrobial properties and antiviral properties are completely different, so when imparting both antimicrobial and antiviral properties to an item, it is necessary to use two types of components, an antimicrobial component and an antiviral component, in combination, but this combination poses problems in terms of drug stability and cost. On the other hand, it is known that diiodomethyl-p-tolylsulfone and zinc oxide have excellent antibacterial and antifungal activities (Patent Documents 1 and 2, etc.), but it has not been reported that the combined use of these two agents exhibits a significantly excellent virus-suppressing effect. [Prior art documents] [Patent documents]

[0003] [Patent Document 1] Japanese Patent Application Publication No. 05-117105 [Patent Document 2] Japanese Patent Application Publication No. 04-093360 Summary of the Invention [Problem to be solved by the invention]

[0004] An object of the present invention is to provide an antiviral agent that not only has an antimicrobial effect against microorganisms such as bacteria and fungi, but also exhibits a virus-suppressing effect. [Means for solving the problem]

[0005] As a result of extensive research into solving the above problems, the present inventors have discovered a combination of antibacterial and antifungal agents that are known to have antimicrobial activity against microorganisms such as bacteria and fungi, which, when used in combination, exhibits a significantly superior virus-inhibiting effect, thereby solving the above problems.

[0006] Specifically, the present invention provides the following: 1. An antiviral agent containing (A) diiodomethyl-p-tolylsulfone and (B) zinc oxide as active ingredients. 2. An antiviral product containing the antiviral agent described in 1. 3. The antiviral agent according to 1, wherein the target virus is an enveloped virus. 4. A method for suppressing viruses using the antiviral agent described in 1. in a subject other than a human. A method for producing an antiviral treated article, comprising blending the antiviral agent described in 5.1 into the article or coating the surface of the article. [Effects of the Invention]

[0007] The antiviral agent of the present invention is useful because it not only exhibits antimicrobial activity against microorganisms such as bacteria and fungi, but also exhibits a significantly excellent virus-suppressing effect when used in combination. In particular, by applying it to various industrial products and materials, it is possible to impart excellent virus suppression effects in addition to microbial control activity. DETAILED DESCRIPTION OF THE INVENTION

[0008] The antiviral agent, antiviral product, virus inhibition method, and method for producing antivirally treated articles of the present invention will be described in detail below. <(A) Diiodomethyl-p-tolylsulfone> The antiviral agent of the present invention contains as an active ingredient (A) diiodomethyl-p-tolylsulfone having the following chemical structure: [ka] The (A) diiodomethyl-p-tolylsulfone (hereinafter sometimes referred to as "DMTS") in the present invention can be produced by known techniques, but commercially available products can also be used. DMTS is a highly effective antifungal agent that is applicable to various indirect food contact applications and is highly safe in terms of skin irritation, etc.

[0009] The content of (A) diiodomethyl-p-tolylsulfone in the antiviral agent of the present invention is not particularly limited and can be determined appropriately depending on the antiviral effect to be exerted. Specific examples of the content of (A) diiodomethyl-p-tolylsulfone include 0.5% by weight or more. From the viewpoint of obtaining a higher antiviral effect, the content is preferably 1% by weight or more, more preferably 5% by weight or more, and even more preferably 10% by weight or more. Furthermore, the upper limit of the content of (A) diiodomethyl-p-tolylsulfone is not particularly limited, but includes, for example, 99.5% by weight or less, more preferably 99% by weight or less, even more preferably 95% by weight or less, and even more preferably 90% by weight or less.

[0010] <(B) Zinc oxide> Zinc oxide, also known as zinc white or zinc white, is used as a white pigment for industrial purposes. In addition, due to the ultraviolet ray shielding effect and visible light transparency of fine particle zinc oxide, it is widely used in various applications such as cosmetics, sunscreens, pharmaceuticals, paints, and plastics. In recent years, zinc oxide has attracted attention for its antibacterial activity, and it has been proposed to impart antibacterial properties to articles. In the present invention, (B) zinc oxide, when used in combination with (A) diiodomethyl-p-tolyl sulfone, not only exhibits the microorganism control activity of each, but also dramatically improves the antiviral activity of (A) diiodomethyl-p-tolyl sulfone. In the present invention, a significantly excellent antiviral property improving effect can be obtained, and therefore, even in a composition in which zinc oxide alone does not exhibit antiviral property, an antiviral property improving effect can be effectively obtained. From this perspective, a suitable example of zinc oxide is zinc oxide having an average particle diameter of 0.01 μm or more. The upper limit of the average particle diameter of zinc oxide is not particularly limited, but from the viewpoint of obtaining a preferable antiviral activity improving effect, it is 50 μm or less, preferably 20 μm or less, more preferably 10 μm or less, even more preferably 5 μm or less, particularly preferably 3 μm or less, and most preferably 1 μm or less. The lower limit of the average particle diameter of zinc oxide is not particularly limited, but is preferably 0.01 μm or more. In this specification, the term "average particle diameter" refers to the 50% cumulative volume particle diameter (D50) measured using a laser diffraction / scattering particle size distribution analyzer.

[0011] The content of zinc oxide (B) in the antiviral agent of the present invention is not particularly limited and can be determined appropriately depending on the antiviral improvement effect to be exerted. From the viewpoint of obtaining a higher antiviral improvement effect, it can be, for example, 0.5% by weight or more, preferably 1% by weight or more. The upper limit of the content of component (B) is not particularly limited and can be, for example, 99.5% by weight or less, preferably 99% by weight or less, more preferably 95% by weight or less, and even more preferably 90% by weight or less.

[0012] In the antiviral agent of the present invention, the ratio of (A) diiodomethyl-p-tolylsulfone to (B) zinc oxide is not particularly limited and is determined by the contents of the above components. However, from the viewpoint of obtaining a more preferable antiviral activity improvement effect, the content of (B) zinc oxide per 1 part by weight of (A) diiodomethyl-p-tolylsulfone is 0.005 parts by weight or more, preferably 0.01 parts by weight or more. Note that the present invention can exhibit a dramatic improvement in antiviral activity by allowing (B) zinc oxide to coexist with (A) diiodomethyl-p-tolylsulfone, in addition to exhibiting the respective microorganism control activities. Therefore, the antiviral agent of the present invention can obtain effective antiviral activity even without blending an extremely large amount of (B) zinc oxide relative to (A) diiodomethyl-p-tolylsulfone. From this viewpoint, the upper limit of the content of (B) zinc oxide per 1 part by weight of (A) diiodomethyl-p-tolylsulfone is, for example, 200 parts by weight or less, preferably 180 parts by weight or less, more preferably 150 parts by weight or less, even more preferably 130 parts by weight or less, and even more preferably 110 parts by weight or less.

[0013] <Target virus> The target viruses of the antiviral agent of the present invention are not particularly limited, and examples thereof include enveloped viruses (viruses having an envelope) such as influenza viruses (e.g., types A and B), rubella viruses, Ebola viruses, coronaviruses, measles viruses, varicella-zoster viruses, herpes viruses, mumps viruses, arboviruses, respiratory syncytial viruses, SARS viruses, hepatitis viruses (e.g., hepatitis A viruses, hepatitis B viruses, hepatitis C viruses, hepatitis D viruses, and hepatitis E viruses), yellow fever viruses, AIDS viruses, rabies viruses, hantaviruses, dengue viruses, Nipah viruses, and lyssaviruses; and non-enveloped viruses (viruses without an envelope) such as adenoviruses, noroviruses, rotaviruses, feline caliciviruses, human papillomaviruses, polioviruses, enteroviruses, coxsackieviruses, human parvoviruses, encephalomyocarditis viruses, polioviruses, and rhinoviruses. Viruses contain genes that are held in an outer protein shell called a capsid, and are therefore broadly classified according to whether their genes are DNA or RNA, and whether the capsid is enveloped or not. Specifically, examples of viruses whose genes are DNA and have an envelope include herpes viruses, those whose genes are DNA and do not have an envelope include adenoviruses, those whose genes are RNA and have an envelope include influenza viruses, and those whose genes are RNA and do not have an envelope include norovirus, feline calicivirus, and poliovirus. The antiviral agent of the present invention can be suitably used to suppress enveloped viruses and non-enveloped viruses. In terms of effectiveness, it is particularly preferred to use it to suppress enveloped viruses, and particularly preferred to use it to suppress influenza viruses.

[0014] <Formulation> The antiviral agent of the present invention can be prepared in various formulations by dissolving or dispersing the active ingredients (A) diiodomethyl-p-tolylsulfone and (B) zinc oxide in various carriers, such as liquid carriers or solid carriers, depending on the purpose, application, etc., to the extent that the virus-inhibiting effect and stability are not affected. Examples of such formulations include liquid formulations such as wettable powders, suspensions, dispersions, emulsions, and oil solutions; solid formulations such as dusts, granules, microcapsules, microspheres, flowable formulations, and foaming agents; semisolid formulations such as pastes and creams; sprays, aerosols, and paints, which can be selected appropriately depending on the purpose of use and the conditions of application. These formulations can be produced by conventional methods. The contents of the active ingredients (A) diiodomethyl-p-tolylsulfone and (B) zinc oxide in the antiviral agent of the present invention are not particularly limited, but can be, for example, 0.001 to 100% by weight, and preferably 0.01 to 80% by weight.

[0015] Examples of the liquid carrier that can be used in the present invention include water; lower alcohols such as methanol, ethanol, n-propanol, isopropanol, and n-butanol; polyhydric alcohols such as ethylene glycol, diethylene glycol, polyethylene glycol, propylene glycol, dipropylene glycol, polypropylene glycol, 1,3-butanediol, 1,4-butanediol, 1,5-pentanediol, ethylene glycol monomethyl ether (methyl carbitol), ethylene glycol monoethyl ether (ethyl carbitol), ethylene glycol monobutyl ether (butyl carbitol), diethylene glycol monomethyl ether, diethylene glycol monoethyl ether, and triethylene glycol butyl ether; acetone, methyl ethyl Examples of suitable liquid carriers include ketones such as ketone, methyl isobutyl ketone, and propylene carbonate; ethers such as dioxane, tetrahydrofuran, and ethyl ether; esters such as ethyl acetate, butyl acetate, isobutyl acetate, 3-methyl-3-methoxybutyl acetate, γ-butyrolactone, dimethyl adipate, dimethyl glutarate, and dimethyl succinate; aromatic solvents such as benzene, toluene, xylene, methylnaphthalene, dimethylnaphthalene, isopropylnaphthalene, diisopropylnaphthalene, ethylbiphenyl, diethylbiphenyl, and solvent naphtha; halogenated hydrocarbon solvents such as carbon tetrachloride, chloroform, and methylene chloride; and polar organic solvents such as dimethylformamide, dimethylacetamide, dimethyl sulfoxide, acetonitrile, and N-methylpyrrolidone. These liquid carriers may be used alone or in combination. Among these liquid carriers, water, ketones such as propylene carbonate, lower alcohols, and polyhydric alcohols are preferred.

[0016] Examples of the solid carrier that can be used in the present invention include diatomaceous earth, mica, clay, kaolin, talc, silica, bentonite, talc powder, rosewood powder, and other talcs, clays such as finely powdered clay, and mineral powders such as calcium carbonate; sulfur powder; urea powder; plant powders such as wood flour and starch; and various carriers commonly used in antiviral agents. These solid carriers are often used as extenders. These solid carriers can also be used alone or in combination. The aerosol preparation can be produced by diluting the active ingredients (A) diiodomethyl-p-tolylsulfone and (B) zinc oxide with an appropriate solvent as needed, and filling the dilution with a propellant into a container. Examples of the solvent include the liquid carriers exemplified above. Examples of the propellant include chlorofluorocarbons and liquefied natural gas.

[0017] The antiviral agent of the present invention may contain various additives as needed depending on the type of formulation, for example, stabilizers such as antioxidants and ultraviolet absorbers; binders; resins capable of forming a coating; emulsifiers, dispersants, spreading agents, wetting agents, penetrating agents; thickeners; flow aids; anti-caking agents; flocculants; ultraviolet scattering agents; moisture removers; colorants, etc.

[0018] Examples of antioxidants include phenolic antioxidants such as 4,4'-thiobis-6-t-butyl-3-methylphenol, butylated hydroxyanisole (a mixture of 2-t-butyl-4-methoxyphenol and 3-t-butyl-4-methoxyphenol), p-octylphenol, mono(or di- or tri)-(α-methylbenzyl)phenol, 2,6-di-t-butyl-p-cresol (BHT), and pentaerythrityl tetrakis[3-(3,5-di-t-butyl-4-hydroxyphenyl)]propionate; amine antioxidants such as N,N'-di-2-naphthyl-p-phenylenediamine; hydroquinoline antioxidants such as 2,5-di(t-amyl)hydroquinoline; sulfur-based antioxidants such as dilaurylthiodipropionate; and phosphorus-based antioxidants such as triphenyl phosphite. Examples of ultraviolet absorbers include benzotriazole compounds such as 2-(2'-hydroxy-5'-methylphenyl)benzotriazole and 2-(2'-hydroxy-4'-n-octoxyphenyl)benzotriazole; benzophenone compounds such as 2-hydroxy-4-methoxybenzophenone and 2-hydroxy-4-n-octoxybenzophenone; salicylic acid compounds such as phenyl salicylate and pt-butylphenyl salicylate; 2-cyano-3,3-diphenylacrylate 2-ethylhexyl, 2-ethoxy-2'-ethyloxalic acid bisanilide, and dimethyl succinate-1-(2-hydroxyethyl)-4-hydroxy-2,2,6,6-tetramethylpiperidine polycondensate. Examples of binders include sodium carboxymethylcellulose, methylcellulose, ethylcellulose, hydroxymethylcellulose, dextrin, pregelatinized starch, polyvinyl alcohol, polyvinylpyrrolidone, sodium lignosulfonate, and potassium lignosulfonate. Examples of resins capable of forming a coating include thermoplastic resins such as polyolefins such as polyethylene and polypropylene, polyvinyl acetate, polyvinyl alcohol, acrylic resins, polyvinyl chloride, styrene-based resins, fluororesins, chlorinated polyolefins, alkyd resins, polyamides, and polyesters; and thermosetting resins such as phenolic resins, urea resins, melamine resins, furan resins, unsaturated polyester resins, and epoxy resins. These resins may be in any form, such as solvent-based or emulsion-based.

[0019] Conventional surfactants such as anionic surfactants and nonionic surfactants can be used as the emulsifier, dispersant, spreading agent, wetting agent, and penetrant. Examples of anionic surfactants include metal soaps, sulfate salts such as sodium alkyl sulfate, alkylbenzenesulfonates such as sodium alkylbenzenesulfonate, alkylnaphthalenesulfonates such as sodium alkylnaphthalenesulfonate (e.g., Newcalgen BX-C, product of Takemoto Yushi Co., Ltd.), dialkyl 2-sulfosuccinate salts such as sodium 2-dialkylsulfosuccinate (e.g., Neocol SW-C, product of Dai-ichi Kogyo Seiyaku Co., Ltd.), polycarboxylic acid surfactants (e.g., Toxanon GR-30, product of Sanyo Chemical Industries, Ltd.), α-olefin sulfonates, polyoxyethylene distyrenated phenyl ether sulfate ammonium salt (e.g., Dixsol 60A, product of Dai-ichi Kogyo Seiyaku Co., Ltd.), sodium lignosulfonate, and potassium lignosulfonate. Examples of nonionic surfactants include polyoxyethylene alkyl ethers, polyoxyethylene alkylaryl ethers (e.g., trade name Noigen (EA-142) manufactured by Dai-ichi Kogyo Seiyaku Co., Ltd.), polyoxyethylene aryl ethers, fatty acid polyhydric alcohol esters, fatty acid polyhydric alcohol polyoxyethylenes, sucrose fatty acid esters, and block copolymers of ethylene oxide and propylene oxide (e.g., trade name Newpol PE-64 manufactured by Sanyo Chemical Industries, Ltd.). Examples of thickeners include polyvinyl alcohol and polyacrylic acid and its salts. Examples of flow aids include organic lubricants such as PAP aids (e.g., isopropyl phosphate), wax, polyethylene, fatty acid metal salts, paraffin, and silicone oil, and inorganic lubricants such as talc. Examples of anti-caking agents include white carbon, diatomaceous earth, magnesium stearate, aluminum oxide, and titanium dioxide. Examples of flocculants include liquid paraffin, ethylene glycol, diethylene glycol, triethylene glycol, and isobutylene polymers (e.g., IP Solvent-2835, manufactured by Idemitsu Kosan Co., Ltd.). Examples of ultraviolet scattering agents include titanium dioxide. Examples of the moisture remover include desiccants such as anhydrous gypsum, silica gel powder, etc. Examples of the colorant include organic or inorganic pigments and dyes.

[0020] Furthermore, the antiviral agent of the present invention may contain known antiseptic and antifungal agents, insecticides, pest repellents, insect growth regulators, and efficacy enhancers.

[0021] The antiviral agent of the present invention can be widely used in various fields requiring a virus-inhibiting effect. The antiviral agent of the present invention can be used to inhibit viruses in various fields, such as industry, cleaning, medicine, and food. In particular, the antiviral agent of the present invention is preferably used as an industrial antiviral agent, and is preferably contained in an antiviral product, particularly an antiviral industrial product. More specific uses of the antiviral agent of the present invention include application to objects other than humans (for example, articles, etc.), specifically, by incorporating the agent into an article or coating the surface of the article. This allows the article to be antivirally treated. That is, the agent exerts a virus-inhibiting effect on viruses already attached to the article, as well as on viruses that will attach to the article in the future, and can further exert a virus-inhibiting effect on viruses already attached to or that will attach to other articles that will come into contact with the article in the future.

[0022] Examples of goods include industrial products and their raw materials used in various fields. Specific examples of industrial products include paints, adhesives, synthetic rubber latex, inks, polyvinyl alcohol films, vinyl chloride films, resin products, gypsum boards, roofing materials, wall materials, flooring materials, building materials, coated paper, wallpaper, floor coverings, office automation equipment, home appliances, air conditioning equipment, vacuum cleaners, desks, chairs, sofas, benches, windows, handrails, handles, seats, automatic ticket gates, automatic ticket vending machines, vending machines, doors, fences, handrails, tableware, cooking utensils, packaging films, packaging bags, bottles, bottles, packaging packs, sinks, toilets, stationery, books, shelves, toothbrushes, mirrors, filters, and masks. Examples of the material include coats, jackets, trousers, skirts, dress shirts, knit shirts, blouses, sweaters, cardigans, nightwear, underwear, diapers, supporters, socks, tights, stockings, hats, scarves, mufflers, collars, stoles, gloves, clothing linings, clothing interlinings, clothing padding, work clothes, uniforms, school uniforms and other clothing, curtains, screen doors, bedding, bedding batting, bedding covers, pillowcases, sheets, mats, carpets, towels, handkerchiefs, wall cloth, band-aids, bandages, and composite materials of these.

[0023] The term "blended into an article" is not particularly limited as long as it means that the active ingredients (A) diiodomethyl-p-tolylsulfone and (B) zinc oxide are contained in the article (preferably, the active ingredients (A) diiodomethyl-p-tolylsulfone and (B) zinc oxide are present on the surface of the article), and can be appropriately selected depending on the type of article. Examples of the blending mode include mixing into the article, kneading in the manufacturing process of the article, and impregnating into the article (for example, an article made of an assembly of fibers).

[0024] The term "coating on the surface of an article" is not particularly limited as long as the active ingredients (A) diiodomethyl-p-tolylsulfone and (B) zinc oxide are present on the surface of the article, and can be appropriately selected depending on the type of article. Examples of coating methods include applying the coating to the surface of the article, spraying the surface of the article, and immersing the surface of the article. Note that coating methods include both methods in which the active ingredients (A) diiodomethyl-p-tolylsulfone and (B) zinc oxide) are fixed to the surface of the article, and methods in which they are not fixed.

[0025] The amount of the antiviral agent of the present invention to be applied can be appropriately selected depending on the mode of use, the type of article to which it is applied, the period for which the virus-suppressing effect is expected, etc. For example, when it is blended into an industrial product, it can be blended so that the amount of the active ingredients, (A) diiodomethyl-p-tolylsulfone and (B) zinc oxide, is 10 to 50,000 mg per 1 kg of the industrial product. [Example]

[0026] The present invention will be explained in more detail below by way of test examples, but the present invention is not limited to these examples. Test examples will demonstrate that the antiviral agent of the present invention exhibits a virus-suppressing effect.

[0027] (1) Preparation of test samples The test samples used were (A) diiodomethyl-p-tolylsulfone (Yotolu DP95, manufactured by Mitsui Chemicals, Inc.) and (B) zinc oxide (fine zinc oxide, manufactured by Sakai Chemical Industry Co., Ltd., particle size: approximately 0.2 μm). (2) Test sample solution Using sterilized water, diiodomethyl-p-tolylsulfone solutions with concentrations of 0.01 wt %, 0.1 wt %, and 1.0 wt % were prepared, and these were used as test sample solutions for (A) diiodomethyl-p-tolylsulfone alone. Zinc oxide suspensions with concentrations of 0.01 wt %, 0.1 wt %, and 1.0 wt % were prepared using sterilized water, and these were used as test sample solutions of (B) zinc oxide alone. Zinc oxide was added to a 0.01 wt% solution of diiodomethyl-p-tolylsulfone in sterilized water to concentrations of 0.01 wt%, 0.1 wt%, and 1.0 wt%, and this was used as a test sample solution containing (A) 0.01 wt% diiodomethyl-p-tolylsulfone and (B) zinc oxide in combination. Zinc oxide was added to a 0.1 wt % solution of diiodomethyl-p-tolylsulfone in sterilized water to concentrations of 0.01 wt %, 0.1 wt %, and 1.0 wt %, and this was used as a test sample solution, which is a specific example of the antiviral agent of the present invention. Zinc oxide was added to a 1.0 wt % solution of diiodomethyl-p-tolylsulfone in sterilized water to concentrations of 0.01 wt %, 0.1 wt %, and 1.0 wt %, and this was used as a test sample solution, which is a specific example of the antiviral agent of the present invention. Sterile water was used as the control test specimen.

[0028] (3) Antiviral test of test sample fluid 1 <Confirmation test for the effect of suppressing enveloped viruses> Influenza virus (ATCC VR-1679) was 8 TCID 50 / mL was used as the test virus suspension. 0.9 mL of the test sample liquid and 0.1 mL of the test virus suspension were mixed in a microtube containing a stir bar. After stirring for 1 hour, 50 μL of the mixture was added to 450 μL of drug inactivation agent (SCDLP liquid medium, Eiken Chemical Co., Ltd.) and mixed. The inactivated mixture was serially diluted 10-fold with dilution medium (E-MEM, Fujifilm Wako Pure Chemical Industries, Ltd.) and used to measure TCID 201 using host cells (MDCK cells, ATCC CCL-34). 50 The viral infectivity was measured by the Median Tissue Culture Infectious Dose method. On the other hand, the virus infectivity of the control test sample was also measured in the same manner. Based on the virus infectivity, the virus inhibitory activity value (Mv) was calculated using the following calculation formula. [Calculation formula] Viral suppression activity value (Mv) = Ig(Vb) - Ig(Vc) Ig(Vb) = Common logarithm of the viral infectivity titer after mixing with the control test sample Ig(Vc) = Common logarithm of the viral infectivity titer after mixing with the test sample solution

[0029] (4) Antiviral activity evaluation method 1 The antiviral activity was evaluated by taking the sum of the virus-inhibiting activity values (Mv) of (A) diiodomethyl-p-tolylsulfone and (B) zinc oxide alone as the "theoretical value" of the antiviral activity of the antiviral agent made by mixing (A) diiodomethyl-p-tolylsulfone and (B) zinc oxide. The virus-inhibitory activity value (Mv) of the antiviral agent, which was a mixture of (A) diiodomethyl-p-tolylsulfone and (B) zinc oxide, was actually measured and calculated and divided by the theoretical value to calculate the "measured value / theoretical value." When the measured value was greater than the theoretical value, i.e., when "measured value / theoretical value" was greater than 1, it could be said that the antiviral activity was enhanced compared to when (A) diiodomethyl-p-tolylsulfone or (B) zinc oxide was used alone, and therefore it was evaluated that a synergistic effect was observed. The virus-inhibiting activity values (Mv) of (A) diiodomethyl-p-tolylsulfone and (B) zinc oxide, each used alone, are shown in Table 1 below, and the virus-inhibiting activity value (Mv) of the antiviral agent, a mixture of (A) diiodomethyl-p-tolylsulfone and (B) zinc oxide, is shown in Table 2 below. The "measured value / theoretical value" at each concentration is summarized in Table 3 below. In Tables 1 to 3, "DMTS" means diiodomethyl-p-tolylsulfone, and "ZnO" means zinc oxide.

[0030] [Table 1]

[0031] [Table 2]

[0032] [Table 3]

[0033] As shown in Table 3, the antiviral agent of the present invention using a combination of (A) diiodomethyl-p-tolylsulfone and (B) zinc oxide had a "measured value / theoretical value" ratio greater than 1 in all cases where the combination was used at 0.01 wt %, 0.1 wt %, and 1.0 wt %, confirming that the agent exerted a synergistic effect in antiviral activity against enveloped viruses. It has also become clear that the antiviral agent of the present invention is extremely useful from the viewpoint of exhibiting practical inhibitory effects against enveloped viruses in addition to its antimicrobial action against microorganisms such as bacteria and fungi.

[0034] (5) Antiviral test of test sample fluid 2 <Confirmation test for non-enveloped virus suppression effect> Each test sample solution and a control test sample were prepared in the same manner as in "(2) Preparation of test sample solutions" above. A confirmation test for virus inhibitory effect was conducted in the same manner as the above "Confirmation test for enveloped virus inhibitory effect," except that the influenza virus in the test virus suspension was replaced with feline calicivirus (ATCC VR-782), the dilution medium E-MEM was replaced with RPMI-1640 (Fujifilm Wako Pure Chemical Industries, Ltd.), the host cells MDCK cells were replaced with CRFK cells (ATCC CCL-94), and the stirring time was changed to 2 hours. Based on the measured virus infectivity, the virus inhibitory activity value (Mv) was calculated using the above formula.

[0035] (6) Antiviral activity evaluation method 2 As in the above "(4) Method 1 for evaluating antiviral activity," the "theoretical value" of antiviral activity and the "measured value / theoretical value" value were calculated. The virus-inhibiting activity values (Mv) of (A) diiodomethyl-p-tolylsulfone and (B) zinc oxide alone are shown in Table 4 below, and the virus-inhibiting activity values (Mv) of the antiviral agent, i.e., the "measured values," of a mixture of (A) diiodomethyl-p-tolylsulfone and (B) zinc oxide are shown in Table 5 below. The "measured value / theoretical value" at each concentration is summarized in Table 6 below. In Tables 4 to 6, "DMTS" means diiodomethyl-p-tolylsulfone, and "ZnO" means zinc oxide.

[0036] [Table 4]

[0037] [Table 5]

[0038] [Table 6]

[0039] As shown in Table 6, the antiviral agent of the present invention using a combination of (A) diiodomethyl-p-tolylsulfone and (B) zinc oxide had a "measured value / theoretical value" ratio greater than 1 in all cases where the combination was used at 0.01 wt %, 0.1 wt %, and 1.0 wt %, confirming that the agent exhibited a synergistic effect in antiviral activity against non-enveloped viruses. It has also become clear that the antiviral agent of the present invention is extremely useful from the viewpoint of exerting practical inhibitory effects against non-enveloped viruses in addition to its antimicrobial action against microorganisms such as bacteria and fungi.

[0040] Test examples will demonstrate that a coating film obtained by adding the antiviral agent of the present invention to a paint exhibits a virus-inhibiting effect. (1) Preparation of test samples As test samples, (A) diiodomethyl-p-tolylsulfone (Yotolu DP95: manufactured by Mitsui Chemicals, Inc.) and (B) the following three types of zinc oxide (B1) to (B3) were used. (B1): FINEX-50, manufactured by Sakai Chemical Industry Co., Ltd., particle size approximately 0.02 μm (B2): Fine zinc oxide, manufactured by Sakai Chemical Industry Co., Ltd., particle size approximately 0.28 μm (B3): Zinc oxide type 1, manufactured by Sakai Chemical Industry Co., Ltd., particle size approximately 0.75 μm (2) Test specimen coating An antiviral paint was prepared by adding an antiviral agent containing (A) diiodomethyl-p-tolylsulfone and (B) zinc oxide (B1) to (B3) from (1) above in the amounts shown in Tables 7 to 9 below to an acrylic resin emulsion (product name "Ultrasol FCE-20," manufactured by Aica Kogyo Co., Ltd.) and mixing uniformly using a mortar and pestle. The resulting antiviral paint was applied to the surface of a PET plate with an applicator to give a coating film thickness of 25 μm, and then dried at room temperature for 3 days to obtain a test sample coating film for a virus suppression effect confirmation test. In addition, a comparative test sample coating was obtained in the same manner except that the antiviral agent of the present invention was not added.

[0041] (3) Test to confirm virus suppression effect The virus suppression effect was confirmed in accordance with the test method (ISO 21702) for evaluating the antiviral effect of non-absorbent surfaces such as plastic and ceramic products. Influenza virus (ATCC VR-1679) was 7 TCID 50 The test virus suspension was prepared at 1 / mL. 0.4 mL of the test virus suspension was dropped onto a 5 cm square test piece (test specimen coating, comparison test specimen coating), which was then covered with a 4 cm square polyethylene film and left to stand at 25°C for 24 hours. After standing, the virus on the test piece was washed out and collected, and the virus infectivity was measured in TCID 50 Measurement was performed using the Median Tissue Culture Infectious Dose method. The virus infectivity of the comparative test sample coating was also measured in the same manner. Based on the virus infectivity, the antiviral activity value (R) was calculated using the following calculation formula. Tables 7 to 9 below show the contents of (A) diiodomethyl-p-tolylsulfone and (B) zinc oxide (B1) to (B3), and the "A" in the following calculation formula. t The "%" in Tables 7 to 9 means % by weight. [Calculation formula] Antiviral activity value (R) = U t -A t U t = Viral infectivity (TCID 50 / cm 2 ) = 5.67 A t = viral infectivity (TCID 50 / cm 2 ) the average of the base 10 logarithms

[0042] [Table 7]

[0043] [Table 8]

[0044] [Table 9]

[0045] As shown in Tables 7 to 9, it was confirmed that the coating films obtained by adding the antiviral agent of the present invention to paints also exhibited excellent antiviral activity. Furthermore, to confirm the synergistic effect of antiviral activity, the sum of the antiviral activity values (R) of (A) diiodomethyl-p-tolylsulfone 0.5 wt % and (B) zinc oxide 5 wt % alone was defined as the "theoretical value" of the antiviral activity of the antiviral agent consisting of a mixture of (A) diiodomethyl-p-tolylsulfone and (B) zinc oxide. The actually measured antiviral activity value (R) of an antiviral agent containing 0.5 wt% of (A) diiodomethyl-p-tolylsulfone and 5 wt% each of (B) zinc oxide (B1) to (B3) was divided by the theoretical value to calculate the "measured value / theoretical value." When the measured value was greater than the theoretical value, i.e., when "measured value / theoretical value" was greater than 1, it could be said that the antiviral activity was enhanced compared to when (A) diiodomethyl-p-tolylsulfone or (B) zinc oxide was used alone, and therefore it was evaluated that a synergistic effect was observed. The "measured value / theoretical value" is summarized in Table 10 below. In Table 10, "%" means % by weight.

[0046] [Table 10]

[0047] As shown in Table 10, the antiviral agent of the present invention, which uses a combination of (A) diiodomethyl-p-tolylsulfone and (B) zinc oxide, exhibited a synergistic effect in antiviral activity, with the "measured value / theoretical value" being greater than 1 even in the coating film obtained when the agent was incorporated into a paint. It has become clear that the antiviral agent of the present invention is extremely useful from the viewpoint of exhibiting a practical inhibitory effect against viruses even when incorporated into paints. [Industrial Applicability]

[0048] The antiviral agent of the present invention is useful because it not only exhibits antimicrobial activity against microorganisms such as bacteria and fungi, but also exhibits a significantly excellent virus-suppressing effect when used in combination. In particular, by applying it to various industrial products and materials, it is possible to impart excellent virus suppression effects in addition to microbial control activity.

Claims

1. An antiviral agent containing (A) diiodomethyl-p-tolylsulfone and (B) zinc oxide as active ingredients.

2. An antiviral product containing the antiviral agent of claim 1.

3. The antiviral agent according to claim 1, wherein the target virus is an enveloped virus.

4. A method for inhibiting viruses using the antiviral agent according to claim 1 in a subject other than humans.

5. A method for producing an antiviral treated article, comprising blending the antiviral agent according to claim 1 into the article or coating the surface of the article with the agent.

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