Antiviral agent

Abstract

To provide an antiviral agent that can exhibit not only an antiviral action but also an antimicrobial action against microorganisms such as bacteria and fungi.SOLUTION: An antiviral agent comprising, as an active ingredient, one or more selected from compounds represented by the general formula (1). (In the formula, R1 represents a C1-4 alkyl group; R2 represents a C1-4 alkyl group, a pyrrolidino group, a piperazino group, or a 4-alkyl substituted piperazino group; Y1 represents N or CX1; Y2 represents N or CX2; X1 represents H; and X2 represents H or a halogen atom. The R1 and the X1 may, together with N to which the R1 is bonded and C to which the X1 is bonded, form a 6-membered ring containing N, where -CH2- contained in the ring may be replaced by -NH- or -N(CH3)-. The R2 and X2 may, together with C to which the R2 is bonded and C to which the X2 is bonded, form a 5-membered ring containing a hetero atom, where -CH2- contained in the ring may be replaced by -O-).SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to an antiviral agent, a method for inhibiting viruses in non-human subjects, and a method for producing an antiviral treated article. [Background technology]

[0002] The spread of viral infections caused by influenza, norovirus, etc. 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 aware of the need to prevent infection. Therefore, there is an increasing demand for imparting not only antimicrobial properties (antibacterial properties, antifungal properties, antialgal properties, etc.) but also antiviral properties to items familiar to 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, quinoline antibacterial agents, which were discovered through a search for antibacterial agents with high activity against a wide range of bacteria, are known to exhibit antibacterial activity by inhibiting DNA gyrase and topoisomerase IV, which are important for bacterial DNA replication (e.g., Patent Document 1, etc.). In contrast to old quinolone antibacterial agents, which only exhibit antibacterial activity mainly against gram-negative bacilli, there are new quinolone antibacterial agents, which are drugs that have dramatically improved antibacterial spectrum and antibacterial activity (Patent Document 2, etc.), but it has not been reported that these quinoline antibacterial agents exhibit virus suppression effects. [Prior art documents] [Patent documents]

[0003] [Patent Document 1] International Publication No. 2014 / 171527 [Patent Document 2] JP 2011-241204 A 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] Means of Solving the Problems The present inventors have conducted intensive research to solve the above problems, and as a result have found that among quinolone compounds known to have antimicrobial activity against microorganisms such as bacteria and fungi, there exists a group of compounds which exhibit virus-inhibiting effects, thereby solving the above problems.

[0006] Specifically, the present invention relates to the following items. 1. An antiviral agent comprising, as an active ingredient, one or more compounds selected from the compounds represented by the following general formula (1) and salts thereof: [ka] (In the formula, R1 represents an alkyl group having 1 to 4 carbon atoms, R2 represents an alkyl group having 1 to 4 carbon atoms, a pyrrolidino group, a piperazino group, or a 4-alkyl-substituted piperazino group, Y1 represents a nitrogen atom or CX1, Y2 represents a nitrogen atom or CX2, X1 represents a hydrogen atom, and X2 represents a hydrogen atom or a halogen atom. R1 and X1 may form a 6-membered ring containing a nitrogen atom together with the nitrogen atom to which R1 is bonded and the carbon atom to which X1 is bonded, and -CH2- contained in the ring may be replaced with -NH- or -N(CH3)-. R2 and X2 may form a 5-membered ring containing a hetero atom together with the carbon atom to which R2 is bonded and the carbon atom to which X2 is bonded, and -CH2- contained in the ring may be replaced with -O-.) 2. The antiviral agent according to 1, wherein the target virus is an enveloped virus. 3. A method for suppressing a virus in a subject other than a human, using the antiviral agent described in 1. A method for producing an antiviral treated article, comprising blending the antiviral agent described in 4.1 into an article or coating the surface of the article. Effect 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 excellent virus suppression effect. In particular, by applying it to various industrial products and industrial materials, it is possible to impart excellent virus suppression effects in addition to microbial control activity. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0008] The antiviral agent, the virus inhibition method, and the method for producing an antiviral treated article of the present invention will be described in detail below. <Regarding the compound represented by general formula (1)> The antiviral agent of the present invention contains, as an active ingredient, one or more compounds selected from the compounds represented by the following general formula (1) and salts thereof: [ka] (In the formula, R1 represents an alkyl group having 1 to 4 carbon atoms, R2 represents an alkyl group having 1 to 4 carbon atoms, a pyrrolidino group, a piperazino group, or a 4-alkyl-substituted piperazino group, Y1 represents a nitrogen atom or CX1, Y2 represents a nitrogen atom or CX2, X1 represents a hydrogen atom, and X2 represents a hydrogen atom or a halogen atom. R1 and X1 may form a 6-membered ring containing a nitrogen atom together with the nitrogen atom to which R1 is bonded and the carbon atom to which X1 is bonded, and -CH2- contained in the ring may be replaced with -NH- or -N(CH3)-. R2 and X2 may form a 5-membered ring containing a hetero atom together with the carbon atom to which R2 is bonded and the carbon atom to which X2 is bonded, and -CH2- contained in the ring may be replaced with -O-.) Examples of the alkyl group having 1 to 4 carbon atoms in R1 or R2 include a methyl group, an ethyl group, an n-propyl group, an i-propyl group, an n-butyl group, an s-butyl group, an i-butyl group, and a t-butyl group. When R1 or R2 is an alkyl group having 1 to 4 carbon atoms, a methyl group or an ethyl group is preferable. When R2 represents a pyrrolidino group, a piperazino group or a 4-alkyl-substituted piperazino group, the 4-alkyl-substituted piperazino group is preferably a 4-methylpiperazino group. Y1 represents a nitrogen atom or CX1, Y2 represents a nitrogen atom or CX2, X1 represents a hydrogen atom, and X2 represents a hydrogen atom or a halogen atom. When X2 represents a halogen atom, it is preferably a fluorine atom. The six-membered ring containing a nitrogen atom when R1 and X1 are taken together with the nitrogen atom to which R1 is bonded and the carbon atom to which X1 is bonded is preferably a six-membered ring containing one oxygen atom and a nitrogen atom to which R1 is bonded, or a six-membered ring containing one oxygen atom, the nitrogen atom to which R1 is bonded, and one further nitrogen atom, and is more preferably the above six-membered ring substituted with a methyl group. The five-membered ring containing a heteroatom when R2 and X2 are taken together with the carbon atom to which R2 is bonded and the carbon atom to which X2 is bonded is preferably a five-membered ring containing two oxygen atoms, and more preferably a 1,3-dioxolane ring. The compound represented by the general formula (1) of the present invention has optical isomers due to the presence of an asymmetric carbon atom, and the present invention includes all optical isomers and racemates. Examples of the salt of the compound represented by the general formula (1) include inorganic base salts and organic base salts. Examples of the inorganic base salt include alkali metal salts such as sodium salt and potassium salt, alkaline earth metal salts such as calcium salt and magnesium salt, and ammonium salt. Examples of the organic base salt include amine salts such as triethylamine salt, pyridine salt, picoline salt, ethanolamine salt, triethanolamine salt, dicyclohexylamine salt, and N,N'-dibenzylethylenediamine salt.

[0009] As the active ingredient of the antiviral agent of the present invention, oxolinic acid, piromidic acid, norfloxacin, marbofloxacin, nalidixic acid, pipemidic acid, ofloxacin, levofloxacin, and salts thereof are preferred, and among these, oxolinic acid, piromidic acid, norfloxacin, marbofloxacin, nalidixic acid, and salts thereof are more preferred, oxolinic acid, piromidic acid, norfloxacin, marbofloxacin, and salts thereof are even more preferred, and oxolinic acid, piromidic acid, norfloxacin, marbofloxacin, and salts thereof are particularly preferred.

[0010] Oxolinic acid has the chemical name “5-ethyl-5,8-dihydro-8-oxo[1,3]dioxolo[4,5-g]quinoline-7-carboxylic acid” and is a compound with the following chemical structure: [ka] Piromic acid has the chemical name "8-ethyl-5,8-dihydro-5-oxo-2-(1-pyrrolidinyl)pyrido[2,3-d]pyrimidine-6-carboxylic acid" and is a compound having the following chemical structure. [ka] Norfloxacin has the chemical name 1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic acid and is a compound having the following chemical structure: [ka]

[0011] Marbofloxacin has the chemical name "9-fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7H-pyrido[3,2,1-ij][4,1,2]benzoxadiazine-6-carboxylic acid" and the following chemical structure: [ka] Nalidixic acid has the chemical name "1,4-dihydro-1-ethyl-4-oxo-7-methyl-1,8-naphthyridine-3-carboxylic acid" and is a compound having the following chemical structure. [ka] Pipemidic acid has the chemical name “8-ethyl-5,8-dihydro-5-oxo-2-(1-piperazinyl)pyrido(2,3-d)pyrimidine-6-carboxylic acid” and is a compound with the following chemical structure: [ka] Ofloxacin has the chemical name "9-fluoro-2,3-dihydro-3α-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7H-pyrido[1,2,3-de]-1,4-benzoxazine-6-carboxylic acid" and is the compound with the chemical structure shown on the left below. Levofloxacin is an optical isomer of ofloxacin. [ka]

[0012] Quinoline antibacterial agents other than the compound represented by formula (1) or a salt thereof of the present invention include compounds having antiviral activity, although their effects are different from those of the compound represented by formula (1). Examples of such compounds include tosufloxacin, sarafloxacin, difloxacin, fleroxacin, lomefloxacin, gatifloxacin, sparfloxacin, danofloxacin, moxifloxacin, garenoxacin, sitafloxacin, orbifloxacin, nadifloxacin, pazufloxacin, and salts thereof. The antiviral agent of the present invention can use one of these compounds or a combination of two or more of them.

[0013] <Target virus> The target viruses of the antiviral agent of the present invention are not particularly limited, and examples thereof include influenza viruses (e.g., types A and B, etc.), rubella viruses, Ebola viruses, coronaviruses, measles viruses, varicella-zoster viruses, herpes viruses, mumps viruses, arboviruses, RS viruses, SARS viruses, hepatitis viruses (e.g., hepatitis A viruses, hepatitis B viruses, hepatitis C viruses, hepatitis D viruses, hepatitis E viruses, etc.), yellow fever viruses, AIDS viruses, rabies viruses, hantaviruses, dengue viruses, Nipah viruses, lyssaviruses, and other enveloped viruses (viruses having an envelope); and non-enveloped viruses (viruses not having an envelope), such as adenoviruses, noroviruses, rotaviruses, feline caliciviruses, human papillomaviruses, polioviruses, enteroviruses, coxsackieviruses, human parvoviruses, encephalomyocarditis viruses, polioviruses, rhinoviruses, and other viruses. Viruses carry their genes, which are held in an outer protein shell called a capsid, and are therefore 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, whose genes are DNA and have a non-enveloped virus include adenoviruses, whose genes are RNA and have an envelope include influenza viruses, and whose genes are RNA and have a non-enveloped virus 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. Among them, in terms of effectiveness, application to suppression of enveloped viruses is preferred, and application to suppression of influenza viruses is particularly preferred.

[0014] <Preparation> The antiviral agent of the present invention can be prepared into various formulations by dissolving or dispersing in various carriers such as liquid carriers and solid carriers, in addition to one or more active ingredients selected from the compounds represented by general formula (1), within a range that does not affect the virus suppression effect and stability depending on the purpose, use, etc. For example, liquid agents such as wettable powders, suspensions, dispersions, emulsions, and oils; solid agents such as powders, granules, microcapsules, microspheres, flowable agents, and foaming agents; semi-solid agents such as pastes and creams; sprays, aerosols, and paints, which can be appropriately selected depending on the purpose of use and the application state. These formulations can be produced by conventional methods. The content of one or more active ingredients selected from the compounds represented by general formula (1) in the antiviral agent of the present invention is not particularly limited, and can be, for example, 0.0001 to 100% by weight, and preferably 0.001 to 50% by weight.

[0015] The liquid carrier that can be used in the present invention includes 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 the liquid carrier 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, dimethylsulfoxide, acetonitrile, and N-methylpyrrolidone. These liquid carriers may be used alone or in combination of two or more. Among these liquid carriers, water, ketones such as propylene carbonate, lower alcohols, and polyhydric alcohols are preferably used.

[0016] Examples of the solid carrier that can be used in the present invention include talcs such as diatomaceous earth, mica, clay, kaolin, talc, silica, bentonite, talc powder, and rosewood powder, clays such as fine clay powder, 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 of two or more. The aerosol agent can be produced by diluting one or more active ingredients selected from the compounds represented by general formula (1) with an appropriate solvent as necessary, 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 fluorocarbons and liquefied natural gas.

[0017] The antiviral agent of the present invention may contain various additives as necessary 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 removing agents; colorants, etc.

[0018] Examples of the antioxidant include phenol-based 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-based antioxidants such as N,N'-di-2-naphthyl-p-phenylenediamine; hydroquinoline-based 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 absorbents 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-diphenylacrylic acid 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 lignin sulfonate, and potassium lignin sulfonate. 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 a solvent type or emulsion type.

[0019] As the emulsifier, dispersant, spreading agent, wetting agent, and penetrant, conventional surfactants such as anionic surfactants and nonionic surfactants can be used. Examples of the anionic surfactants include metal soaps, sulfate ester salts such as sodium alkyl sulfate, alkylbenzene sulfonates such as sodium alkylbenzene sulfonate, alkylnaphthalene sulfonates such as sodium alkylnaphthalene sulfonate (e.g., manufactured by Takemoto Oil Co., Ltd., trade name New Calgen BX-C), 2-sulfosuccinic acid dialkyl salts such as sodium dialkyl 2-sulfosuccinate (e.g., manufactured by Dai-ichi Kogyo Seiyaku Co., Ltd., trade name Neocol SW-C), polycarboxylic acid type surfactants (e.g., manufactured by Sanyo Chemical Industries Co., Ltd., trade name Toxanon GR-30), α-olefin sulfonates, polyoxyethylene distyrenated phenyl ether sulfate ammonium salt (e.g., manufactured by Dai-ichi Kogyo Seiyaku Co., Ltd., trade name Dixsol 60A), sodium ligninsulfonate, and potassium ligninsulfonate. Examples of nonionic surfactants include polyoxyethylene alkyl ethers, polyoxyethylene alkyl aryl ethers (e.g., trade name Noigen (EA-142) manufactured by Daiichi Kogyo Seiyaku Co., Ltd.), polyoxyethylene aryl ethers, fatty acid polyhydric alcohol esters, fatty acid polyhydric alcohol polyoxyethylene, 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, polyacrylic acid and its salts, and 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., Idemitsu Kosan Co., Ltd., product name IP Solvent-2835). Examples of ultraviolet scattering agents include titanium dioxide. Examples of moisture removers include desiccants such as anhydrous gypsum and silica gel powder. Examples of colorants 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 suppression effect. The antiviral agent of the present invention can be used to suppress 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. More specific examples of the use of the antiviral agent of the present invention include application to objects other than humans (e.g., articles, etc.), specifically, incorporation into an article, coating on the surface of an article, etc. This allows the article to be antivirally treated. That is, the antiviral agent exerts a virus-suppressing effect on viruses already attached to the article, exerts a virus-suppressing effect on viruses that will be attached to the article in the future, and further exerts a virus-suppressing effect on viruses already attached to other articles that will come into contact with the article in the future or viruses that will be attached to them in the future.

[0022] Examples of the 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, polyvinyl chloride films, resin products, gypsum boards, roofing materials, wall materials, flooring materials, fittings, coated paper, wallpaper, floor coverings, office automation equipment, home appliances, air conditioning equipment, vacuum cleaners, desks, chairs, sofas, benches, windows, hanging straps, 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, masks, Examples of the material include coats, jackets, trousers, skirts, dress shirts, knit shirts, blouses, sweaters, cardigans, nightwear, undergarments, 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 material, 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 is an embodiment in which one or more active ingredients selected from the compounds represented by general formula (1) are contained in the article (preferably an embodiment in which one or more active ingredients selected from the compounds represented by general formula (1) are present on the surface of the article), and can be appropriately selected depending on the type of article. Examples of the embodiment include mixing into the article, kneading in the manufacturing process of the article, and impregnating the article (for example, an article made of an accumulation of fibers).

[0024] The term "coating on the surface of an article" is not particularly limited as long as it is an embodiment in which one or more active ingredients selected from the compounds represented by general formula (1) are present on the surface of the article, and can be appropriately selected depending on the type of article. Examples of the coating embodiment include applying the coating to the surface of the article, spraying the surface of the article, and immersing the surface of the article. The coating embodiment includes both an embodiment in which one or more active ingredients selected from the compounds represented by general formula (1) are fixed on the surface of the article, and an embodiment 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 during which the virus suppression effect is expected, etc. For example, when it is blended with an industrial product, it can be blended so that the amount of one or more active ingredients selected from the compounds represented by general formula (1) is 10 to 50,000 mg per 1 kg of the industrial product. EXAMPLES

[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 exerts a virus-suppressing effect.

[0027] (1) Test specimen Oxolinic acid, piromidic acid, norfloxacin, marbofloxacin, nalidixic acid, pipemidic acid, and levofloxacin were used as test samples. All of these compounds were prepared using reagents manufactured by Fujifilm Wako Pure Chemical Industries, Ltd. (2) Test sample liquid To a sterilized centrifuge tube, 0.01 g of each test sample, 0.05 g of dimethyl sulfoxide (hereinafter referred to as "DMSO"), and 0.84 g of Dulbecco's phosphate buffered saline (PBS, Fujifilm Wako Pure Chemical Industries, Ltd.) were added to prepare test sample solution A with a test sample concentration of 1.1%. In addition, 0.05 g of each test sample, 0.05 g of DMSO, and 0.80 g of Dulbecco's phosphate buffered saline (PBS, Fujifilm Wako Pure Chemical Industries, Ltd.) were added to a sterilized centrifuge tube to prepare test sample solution B with a test sample concentration of 5.5%. A sample containing 0.05 g of DMSO and 0.85 g of Dulbecco's phosphate buffered saline (PBS, Fujifilm Wako Pure Chemical Industries, Ltd.) was used as a control test sample.

[0028] (3) Antiviral test of test sample fluid <Confirmation test of envelope virus suppression effect> Influenza virus (ATCC VR-1679) was incubated for 10 8 TCID 50 / mL was used as the test virus suspension. 0.9 mL of test specimen solution A or test specimen solution B and 0.1 mL of test virus suspension were mixed in a microtube containing a stir bar, and the mixture with a final test specimen concentration of approximately 1% or approximately 5% was stirred for 2 hours or 24 hours. After stirring for the specified time, 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 diluted 10-fold in dilution medium (E-MEM, Fujifilm Wako Pure Chemical Industries, Ltd.) and used as a TCID 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 according to the following formula. [Calculation formula] Virus suppression activity value (Mv) = Ig(Vb) - Ig(Vc) Ig(Vb) = Common logarithm of the viral infectivity after mixing with the control test specimen Ig(Vc) = Common logarithm of the viral infectivity after mixing with the test sample liquid The obtained virus inhibitory activity values ​​(Mv) are shown in Table 1 below. A virus suppression activity value (Mv) of approximately "1" or more was determined to have an envelope virus suppression effect, and a value of approximately "2" or more was determined to have a practical envelope virus suppression effect.

[0029] [Table 1]

[0030] As shown in Table 1, it was confirmed that the compounds represented by general formula (1) of oxolinic acid, piromidic acid, norfloxacin, marbofloxacin, nalidixic acid, pipemidic acid, and levofloxacin, which are the active ingredients of the antiviral agent of the present invention, have a virus inhibitory activity value (Mv) of approximately "2" or more both after 2 hours and 24 hours at a final concentration of 5%, and exhibit a practical inhibitory effect against enveloped viruses. Among them, it was also revealed that oxolinic acid, piromidic acid, norfloxacin, marbofloxacin, and nalidixic acid, which are the active ingredients of the antiviral agent of the present invention, are very useful not only from the viewpoint of practical inhibitory effect against enveloped viruses but also from the viewpoint of formulation stability in industrial applications.

[0031] <Confirmation test of non-enveloped virus suppression effect> A confirmation test of the virus suppression effect was carried out in the same manner as the above "Confirmation test of the envelope virus suppression effect" except that the influenza virus in the test virus suspension was replaced with feline calicivirus (ATCC VR-782), the E-MEM in the dilution medium was replaced with RPMI-1640 (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.), and the host cell MDCK cells were replaced with CRFK cells (ATCC CCL-94). Based on the measured virus infectivity, the virus suppression activity value (Mv) was calculated using the above formula. The obtained virus inhibitory activity values ​​(Mv) are summarized in Table 2 below. A virus inhibitory activity value (Mv) of approximately "1" or more was determined to have a non-enveloped virus inhibitory effect, and a virus inhibitory activity value of approximately "2" or more was determined to have a practical non-enveloped virus inhibitory effect.

[0032] [Table 2]

[0033] As shown in Table 2, it was confirmed that oxolinic acid, piromidic acid, norfloxacin, marbofloxacin, nalidixic acid, pipemidic acid, and levofloxacin, which are compounds represented by general formula (1) and are active ingredients of the antiviral agent of the present invention, have an inhibitory effect against non-enveloped viruses. Among them, it was revealed that oxolinic acid, piromidic acid, norfloxacin, marbofloxacin, and nalidixic acid, which are active ingredients of the antiviral agent of the present invention, are extremely useful not only from the viewpoint of practical inhibitory effect against non-enveloped viruses but also from the viewpoint of formulation stability in industrial applications. In particular, oxolinic acid, piromidic acid, and nalidixic acid have a virus-inhibiting activity value (Mv) of approximately "2" or more at final concentrations of both 1% and 5%, and exhibit a practical effect of inhibiting non-enveloped viruses, making them suitable as active ingredients for the antiviral agent of the present invention. [Industrial Applicability]

[0034] 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 excellent virus suppression effect. In particular, in industrial applications where the composition is applied to various industrial products and industrial materials, it is possible to obtain excellent virus suppression effects in addition to microbial control activity.

Claims

1. An antiviral agent comprising, as an active ingredient, one or more compounds selected from compounds represented by the following general formula (1) and salts thereof: 【Chemistry 1】 (In the formula, R １ represents an alkyl group having 1 to 4 carbon atoms; R ２ represents an alkyl group having 1 to 4 carbon atoms, a pyrrolidino group, a piperazino group, or a 4-alkyl-substituted piperazino group; Y １ is a nitrogen atom or CX １ represents Y ２ is a nitrogen atom or CX ２ represents X １ represents a hydrogen atom, and X ２ represents a hydrogen atom or a halogen atom. １ and the above X １ is the R １ and the nitrogen atom to which X is bonded. １ may form a 6-membered ring containing a nitrogen atom together with the carbon atom to which it is bonded, and —CH ２ - is -NH- or -N(CH ３ )- may be replaced by. ２ and the above X ２ is the R ２ and the carbon atom to which X is bonded ２ may form a 5-membered ring containing a heteroatom together with the carbon atom to which it is bonded, and —CH ２ - may be replaced with -O-.)

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

3. A method for inhibiting a virus, comprising using the antiviral agent according to claim 1 on an organism other than humans.

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

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