Virus inactivator

Abstract

To provide a virus inactivator that enables the inactivation of viruses present in the environment. [Solution] A virus inactivator comprising (A) maleic acrylate copolymer or a salt thereof, and (B) at least one surfactant selected from anionic surfactants, cationic surfactants, and amphoteric surfactants as active ingredients.

Description

Technical Field

[0001] The present invention relates to a virus inactivator and a virus inactivation method.

Background Art

[0002] Viral infectious diseases typified by viral respiratory infections and infectious gastroenteritis (viral gastroenteritis) mainly spread when brought into the living space by an infected person, directly from the patient or through the environment including human fingers, clothes, various instruments and members, facilities such as walls and air conditioners. Therefore, it is considered effective to prevent the spread of infection by removing or inactivating viruses by washing and disinfecting fingers, clothes, and various instruments and members to which viruses can adhere, and by inactivating viruses that have splashed into the living space and viruses floating in the air as aerosols.

[0003] Conventionally, ethanol (high concentration and acidic or alkaline), chlorine-based disinfectants (such as sodium hypochlorite), iodine agents, aldehyde agents (such as glutaral), peracetic acid preparations, etc. have been used for the purpose of inactivating viruses. However, these general disinfectants have high irritability to mucous membranes and skin, so their uses are limited due to safety problems. In addition, the time required for virus inactivation is long, and sufficient effects cannot be obtained at room temperature, or the effects may be reduced by combined use with other bases such as activators. Furthermore, as a method of chemically inactivating viruses present in space, spraying chlorine dioxide has also been devised, but its effect is not certain.

[0004] The acrylic acid-maleic acid copolymer is one of the water-soluble polymers of the acrylic acid type, and has excellent performance regarding adsorption to inorganic salts by carboxyl groups and dispersive force by ionization, and thus is used in applications such as detergent builders, metal ion sequestering agents, scale (calcium carbonate, phosphates, etc.) inhibitors. On the other hand, Patent Document 1 reports that a disinfectant formulation containing an acidic polymer and an anionic surfactant, which include maleic acid as a constituent unit, possesses both antiviral and antibacterial activity. However, it is completely unknown that acrylate-maleic acid copolymers, or combinations of these polymers with surfactants, have virus-inactivating properties. [Prior art documents] [Patent Documents]

[0005] [Patent Document 1] Special Publication No. 2011-511764 [Overview of the project] [Problems that the invention aims to solve]

[0006] The present invention relates to providing a virus inactivator that enables the inactivation of viruses present in the environment. [Means for solving the problem]

[0007] The inventors have discovered that a combination of acrylate-maleic acid copolymer and a surfactant has the effect of inactivating viruses such as human norovirus, and that this is useful as a virus inactivator.

[0008] In other words, the present invention relates to a virus inactivator comprising (A) maleic acrylate copolymer or a salt thereof, and (B) at least one surfactant selected from anionic surfactants, cationic surfactants, and amphoteric surfactants as active ingredients. The present invention also relates to a method for inactivating viruses, comprising applying (A) a maleic acrylate copolymer or a salt thereof, and (B) at least one surfactant selected from anionic surfactants, cationic surfactants, and amphoteric surfactants, or a composition containing the same, to an object suspected of viral contamination. The present invention also provides a virus inactivation composition comprising (A) maleic acrylate copolymer or a salt thereof, and (B) at least one surfactant selected from anionic surfactants, cationic surfactants, and amphoteric surfactants as active ingredients, The composition contains 0.01% by mass or more and 10% by mass or less, and the mass ratio of component (A) to component (B) [(B) / (A)] is 0.03 or more and 250 or less. This invention relates to a virus inactivation composition for use on objects suspected of viral contamination, which is diluted with water to form a diluted solution containing component (A) at a concentration of 10 ppm to 1000 ppm, and applied to the object. The present invention also provides a virus inactivation composition comprising (A) maleic acrylate copolymer or a salt thereof, and (B) at least one surfactant selected from anionic surfactants, cationic surfactants, and amphoteric surfactants as active ingredients, The present invention relates to a virus inactivation composition in which the concentration of component (A) in the composition is 10 ppm or more and 1000 ppm or less, and the mass ratio of component (A) to component (B) [(B) / (A)] is 0.03 or more and 250 or less. [Effects of the Invention]

[0009] The virus inactivating agent or virus inactivating composition of the present invention can inactivate viruses attached to hands, hard and soft surfaces in the living environment, viruses dispersed in airborne droplets in living spaces, and prevent or reduce the spread of infection caused by such viruses. [Modes for carrying out the invention]

[0010] In the present invention, (A) maleic acrylate copolymer or a salt thereof, and (B) at least one surfactant selected from anionic surfactants, cationic surfactants, and amphoteric surfactants (hereinafter also simply referred to as (B) surfactant) are used as active ingredients for virus inactivation. (A) Acrylates-maleic acid copolymer is a copolymer containing constituent units derived from acrylic acid and constituent units derived from maleic acid. The polymerization mode of acrylics-maleic acid copolymer is not particularly limited and may be random copolymerization, block copolymerization, etc., but random copolymerization is preferred. In the acrylic acid-maleic acid copolymer of the present invention, acrylic acid and maleic acid are essential components as monomers. Maleic acid and acrylic acid may be partially or completely neutralized. Maleic anhydride may also be used as maleic acid. Furthermore, in the present invention, monomers other than acrylic acid (salt) and maleic acid (salt) may be included as monomer components, as long as they do not impair the effects of the present invention. Such monomers can be copolymerized with acrylic acid (salt) or maleic acid (salt), for example, unsaturated monocarboxylic acid monomers such as methacrylic acid and crotonic acid; neutralized products obtained by partially or completely neutralizing the above unsaturated monocarboxylic acid monomers with monovalent metals, divalent metals, ammonia, organic amines, etc.; unsaturated dicarboxylic acid monomers such as fumaric acid, itaconic acid, and citraconic acid; neutralized products obtained by partially or completely neutralizing the above unsaturated dicarboxylic acid monomers with monovalent metals, divalent metals, ammonia, organic amines, etc.; amide monomers such as (meth)acrylamide and t-butyl(meth)acrylamide; (meth) Hydrophobic monomers such as acrylic acid esters, styrene, 2-methylstyrene, and vinyl acetate; unsaturated sulfonic acid monomers such as vinyl sulfonic acid, allyl sulfonic acid, methallyl sulfonic acid, styrene sulfonic acid, 2-acrylamido-2-methylpropanesulfonic acid, 3-alyloxy-2-hydroxypropanesulfonic acid, sulfoethyl (meth)acrylate, sulfopropyl (meth)acrylate, 2-hydroxysulfopropyl (meth)acrylate, and sulfoethylmaleimide; neutralized products obtained by partially or completely neutralizing the above unsaturated sulfonic acid monomers with monovalent metals, divalent metals, ammonia, organic amines, etc.3-Methyl-2-buten-1-ol (prenol), 3-methyl-3-buten-1-ol (isoprenol), 2-methyl-3-buten-2-ol (isoprene alcohol), 2-hydroxyethyl (meth)acrylate, polyethylene glycol mono(meth)acrylate, polypropylene glycol mono(meth)acrylate, polyethylene glycol monoisoprenol ether, polypropylene glycol monoisoprenol ether, polyethylene glycol monoallyl ether, polypropylene glycol monoallyl ether, glycerol monoallyl ether Examples include, but are not limited to, hydroxyl-containing unsaturated monomers such as tel, α-hydroxyacrylic acid, N-methylol(meth)acrylamide, glycerol mono(meth)acrylate, and vinyl alcohol; cationic monomers such as dimethylaminoethyl(meth)acrylate and dimethylaminopropyl(meth)acrylamide; nitrile monomers such as (meth)acrylonitrile; and phosphorus-containing monomers such as (meth)acrylamidemethanephosphonic acid, (meth)acrylamidemethanephosphonic acid methyl ester, and 2-(meth)acrylamide-2-methylpropanephosphonic acid. These monomers may be used individually or in combination of two or more. Examples of salts of maleic acrylate copolymer include alkali metal salts, alkaline earth metal salts, ammonium salts, alkyl or alkenylammonium salts having 1 to 22 carbon atoms, alkyl or alkenyl-substituted pyridinium salts having 1 to 22 carbon atoms, alkanolammonium salts having 1 to 22 carbon atoms, and basic amino acid salts. Preferably, alkali metal salts are used, and more preferably, sodium salts.

[0011] The weight-average molecular weight of the maleic acrylate copolymer or its salt is preferably 1,000 to 1,000,000, from the viewpoint of virus inactivation effect. The weight-average molecular weight can be measured, for example, by gel permeation chromatography (GPC).

[0012] The molar ratio (acrylic acid:maleic acid) of acrylic acid-derived constituent units to maleic acid-derived constituent units constituting the acrylic acid-maleic acid copolymer or its salt is preferably 0.20:0.80 to 0.80:0.20, from the viewpoint of virus inactivation effect.

[0013] The acrylic acid maleic acid copolymer or its salts can be commercially available. Furthermore, based on previously reported information, it is possible to produce the same substance as the commercially available product, or a composition containing it, through chemical synthesis.

[0014] In the present invention, the concentration of (A) maleic acrylate copolymer or its salt (in terms of maleic acrylate copolymer) at the time of application of the virus inactivating agent to an object suspected of being contaminated with viruses (hereinafter also referred to as the object to be treated) is preferably 10 ppm (by mass) or more, more preferably 30 ppm or more, and even more preferably 40 ppm or more, from the viewpoint of further improving the virus inactivation effect. There is no particular upper limit, but from the viewpoint of usability and properties when applied to the object to be treated, it is preferably 1000 ppm or less, and more preferably 300 ppm or less. By combining (A) maleic acrylate copolymer or its salt with (B) surfactant, a virus inactivation effect can be observed even at a concentration of (B) surfactant in which the virus inactivation effect is insufficient with (B) surfactant alone. The concentration of component (A) may be the concentration of component (A) contained in the virus inactivation composition itself, as described later, or it may be the concentration of component (A) in the liquid when applied to the object to be treated.

[0015] (B) The surfactant is at least one selected from anionic surfactants, cationic surfactants, and amphoteric surfactants. When combining multiple surfactants, two or more selected from anionic surfactants, cationic surfactants, and amphoteric surfactants may be used in combination. In addition, anionic surfactants may be used in combination with other anionic surfactants, cationic surfactants with other cationic surfactants, or amphoteric surfactants with other amphoteric surfactants.

[0016] As anionic surfactants, sulfate-based, sulfonate-based, and carboxylate-based ones are preferable. For example, alkyl sulfates, alkylbenzene sulfonates, internal olefin sulfonates having 10 to 18 carbon atoms, polyoxyalkylene alkyl ether sulfates, polyoxyalkylene alkenyl ether sulfates, and polyoxyalkylene alkyl aryl ether sulfates, fatty acid salts, pyrophosphates, lauryl phosphoric acid, polycarboxylic acid-type polymers, polyoxyethylene alkylene alkyl acetic acid, formalin condensates of aromatic sulfonates, polyoxyethylene distyrenated ether sulfates, alkyl diphenyl ether disulfonates, dialkyl sulfosuccinates, alkyl naphthalene sulfonates, and the like can be mentioned. Examples of salts include alkali metal salts, alkaline earth metal salts, ammonium salts, organic ammonium salts, and basic amino acid salts. The number of carbon atoms in the alkyl part etc. (excluding internal olefin sulfonates having 10 to 18 carbon atoms) is preferably 8 or more, more preferably 10 or more, from the viewpoint of surfactant action, and is preferably 24 or less, more preferably 22 or less, still more preferably 20 or less.

[0017] As cationic surfactants, quaternary ammonium-type ones are preferable. For example, alkyl benzyl dimethyl ammonium salts, dialkyl dimethyl ammonium salts, alkyl trimethyl ammonium salts, triethanolamine diester quaternary salts, and the like can be mentioned. The number of carbon atoms in the alkyl part is preferably 8 or more, more preferably 10 or more, from the viewpoint of surfactant action, and is preferably 22 or less, more preferably 20 or less, still more preferably 18 or less.

[0018] As amphoteric surfactants, betaine-type and amine oxide-type ones are preferable. For example, carboxybetaines such as alkyl carboxybetaine and alkyl(amidopropyl)carboxybetaine, sulfobetaines such as alkyl sulfobetaine, alkyl(amidopropyl)sulfobetaine, and alkyl hydroxy sulfobetaine, and alkyl dimethyl amine oxide, and the like can be mentioned. From the viewpoint of surface activity, the number of carbon atoms in the alkyl moiety is preferably 6 or more, more preferably 8 or more, still more preferably 10 or more, and is preferably 22 or less, more preferably 20 or less, still more preferably 18 or less.

[0019] In the present invention, from the viewpoint of enhancing the virus-inactivating effect, it is preferable to use at least one selected from anionic surfactants, amphoteric surfactants, and cationic surfactants as the surfactant. As the anionic surfactant, alkyl sulfate salts, alkylbenzene sulfonate salts, internal olefin sulfonate salts having 10 to 18 carbon atoms, polyoxyethylene alkyl ether sulfate salts, and fatty acid salts are preferable. As the amphoteric surfactant, alkyldimethylamine oxides and alkyl hydroxysulfobetaines are preferable. As the cationic surfactant, alkylbenzyldimethylammonium salts are preferable. Commercially available surfactants can be used. Also, based on previously reported information, it is possible to produce the same substance as the commercially available product or a composition containing the same by chemical synthesis.

[0020] In the present invention, from the viewpoint of improving the virus-inactivating effect, the concentration of the surfactant (B) at the time of applying the virus inactivator to the treatment target is preferably 10 ppm or more, more preferably 50 ppm or more, still more preferably 100 ppm or more. Also, from the viewpoint of the usability when applying to the treatment target, etc., it is preferably 30000 ppm or less, more preferably 25000 ppm or less. When the surfactant (B) is at least one surfactant selected from anionic surfactants and amphoteric surfactants, the concentration of the surfactant (B) is preferably 50 ppm or more, more preferably 100 ppm or more, still more preferably 200 ppm or more, particularly preferably 400 ppm or more from the viewpoint of improving the virus-inactivating effect. Also, from the viewpoint of the usability when applying to the treatment target, etc., it is preferably 30000 ppm or less, more preferably 25000 ppm or less. (B) When the surfactant is a cationic surfactant, the concentration of the cationic surfactant is preferably 5 ppm or more, more preferably 7 ppm or more, and preferably 50 ppm or less, and more preferably 10 ppm or less, from the viewpoint of balancing improved virus inactivation effect with ease of use when applied to the target of treatment. The concentration of component (B) may be the concentration of component (B) in the virus inactivation composition described later, or it may be the concentration of component (B) in the liquid when applied to the target of treatment.

[0021] As shown in the examples described later, the combination of (A) maleic acrylate copolymer or a salt thereof and (B) a surfactant exhibits excellent virus inactivation effects against feline calicivirus and human norovirus. Moreover, this effect is superior to the effects of maleic acrylate copolymer and the surfactant individually. Therefore, a combination of (A) maleic acrylate copolymer or a salt thereof and (B) a surfactant can serve as a virus inactivator that inactivates viruses, and can also be used to manufacture virus inactivators. Furthermore, a combination of (A) maleic acrylate copolymer or a salt thereof and (B) a surfactant can be used to inactivate viruses.

[0022] From the viewpoint of improving the virus inactivation effect, the combination of (A) maleic acrylate copolymer or a salt thereof and (B) surfactant has a mass ratio of component (B) to component (A) [(B) / (A)] which is preferably 0.03 or more, more preferably 0.2 or more, even more preferably 0.5 or more, and especially preferably 1 or more, and from the viewpoint of compatibility with the feel of the composition, it is preferably 300 or less, and more preferably 250 or less. (B) Surfactants include compounds that have bactericidal effects or protein denaturation effects, but their content may be limited from the viewpoint of the feel of the composition. According to the present invention, by including (A) maleic acrylate copolymer or a salt thereof, the virus inactivation effect can be improved without increasing the content of surfactant (B).

[0023] The viruses targeted by the virus inactivator in this invention include all types of viruses, regardless of the type of nucleic acid (RNA, DNA) and whether or not they have an envelope. Enveloped viruses include those with RNA as their nucleic acid, such as influenza virus, coronavirus, SARS coronavirus, SARS coronavirus-2, RSV, mumps virus, lassa virus, dengue virus, rubella virus, and human immunodeficiency virus, and those with DNA as their nucleic acid, such as human herpesvirus, vaccinia virus, and hepatitis B virus. Furthermore, examples of viruses that do not have an envelope include those with RNA as their nucleic acid, such as norovirus, poliovirus, echovirus, hepatitis A virus, hepatitis E virus, rhinovirus, astrovirus, rotavirus, coxsackievirus, enterovirus, and sapovirus, and those with DNA as their nucleic acid, such as adenovirus, B19 virus, papovavirus, and human papillomavirus. SARS-CoV-2 (Severe acute respiratory syndrome coronavirus 2) is a SARS-related coronavirus that causes acute respiratory illness (COVID-19). Of these, norovirus is preferred.

[0024] Norovirus includes HNV (human norovirus), FCV (feline calicivirus), MNV (mouse norovirus), and others. Noroviruses are divided into seven gene groups (genogroups, GI to GVII) based on the homology of their genome base sequences. The HNVs that infect humans are GI9 types (GI.1, GI.2, GI.3, GI.4, GI.5, GI.6, GI.7, GI.8, GI.9), GII19 types (GII.1, GII.2, GII.3, GII.4, GII.5, GII.6, GII.7, GII.8, GII.9, GII.10, GII.12, GII.13, GII.14, GII.15, GII.16, GII.17, GII.20, GII.21, GII.22), and GIV1 type (GIV.1). However, the HNV in this invention may be any of these genotypes.

[0025] In the present invention, virus inactivation means reducing or eliminating the activity of the virus and thereby eliminating its ability to infect host cells. The virus inactivation effect can be confirmed, for example, by bringing the test product into contact with the virus, infecting host cells with the virus, and measuring the viral infectivity titer. Here, the host cell can be any cell in which the target virus can proliferate. For example, for feline calicivirus, cat kidney-derived cell lines (CRFK) can be used; for adenovirus, human laryngeal cancer-derived cells (HEp-2) can be used; for influenza virus, canine kidney cells (MDCK), African green monkey kidney epithelial cells (Vero), or duck embryonic stem cell-derived cell lines (EB66) can be used; and for human coronavirus, human ileocecal adenocarcinoma cells (HCT-8), African green monkey kidney epithelial cells (VeroE6), or human liver cancer-derived cell lines (Huh7) can be used. Furthermore, the human norovirus inactivation effect can be evaluated by a system in which human intestinal organoids are cultured in three dimensions on an extracellular matrix, and then differentiated to obtain intestinal epithelial cells, which are then infected with HNV (see Examples).

[0026] In the present invention, (A) maleic acrylate copolymer or its salt and (B) surfactant may be applied in any order or simultaneously. If they are not applied simultaneously, the interval between their application can be appropriately selected as long as it enhances the virus inactivation effect of the maleic acrylate copolymer or its salt, or the surfactant. An agent comprising (A) maleic acrylate copolymer or a salt thereof and (B) a surfactant may be formulated as a single dosage form of a combination agent, or as a kit in which the individual formulations can be used simultaneously or separately at intervals. In particular, it is preferable to formulate the combination agent as a single dosage form and apply them simultaneously.

[0027] The virus inactivator in the present invention may be in the form of using only (A) maleic acrylate copolymer or a salt thereof and (B) a surfactant, or it may be in the form of a composition (for example, a virus inactivation composition) containing (A) maleic acrylate copolymer or a salt thereof and (B) a surfactant. That is, the virus inactivator in the present invention may be a virus inactivation composition that exhibits a virus inactivation effect, or it may be a material or formulation for incorporating into such a composition. The virus inactivation composition may be in an undiluted form or a diluted form. The undiluted form is applied to the target object without dilution and used for virus inactivation. The diluted form is diluted with a suitable medium such as water to achieve an active ingredient concentration in which (A) maleic acrylate copolymer or a salt thereof and (B) surfactant exert a virus inactivation effect, and is used for virus inactivation of the target object. The preferred active ingredient concentration for which a virus inactivation effect is exerted is as described above.

[0028] The combination of (A) maleic acrylate copolymer or a salt thereof and (B) surfactant can be used in either a liquid or gas phase, but it is preferable to use it in a liquid phase from the viewpoint of virus inactivation effect.

[0029] The above-mentioned virus inactivation compositions include those used in liquid or gaseous form. The virus inactivation composition used in the liquid phase may contain (A) maleic acrylate copolymer or a salt thereof and (B) a surfactant, as well as antimicrobial substances such as a base, hypochlorous acid, hydrogen peroxide, and silver ion compounds, disinfectants (such as triclosan and isopropylmethylphenol), and surfactants other than component (B). The virus inactivation composition is also prepared by appropriately blending additives such as chelating agents, humectants, lubricants, builders, buffers, abrasives, electrolytes, bleaches, fragrances, dyes, foaming control agents, corrosion inhibitors, essential oils, thickeners, pigments, gloss enhancers, enzymes, detergents, solvents, dispersants, polymers, silicones, and hydrophobic substances. The form of such a composition may be, but is not limited to, liquid, emulsion, cream, lotion, paste, gel, sheet (base-supported), or oil. The virus inactivation composition can be appropriately incorporated into various cleaning agents (laundry detergents, household cleaning agents, dishwashing detergents, hair washes, hand washes, body washes, etc.), disinfectants, sanitary product compositions, etc. When using the virus inactivation composition of the present invention in laundry detergents, dishwashing detergents, etc., the virus inactivation composition can be used after diluting with water. In this case, the dilution ratio is preferably 10 times by mass or more, more preferably 100 times by mass or more, even more preferably 800 times by mass or more, and also preferably 5000 times by mass or less, and more preferably 4000 times by mass or less. Since the virus inactivation effect is achieved even with such dilution, the concentration of the active ingredient in the virus inactivation composition can be appropriately designed.

[0030] Examples of the above-mentioned sanitary product compositions include lotions, creams, shampoos, hair conditioners, hand soaps, body washes, facial cleansers, bath additives, foams, antiperspirants, deodorants, underarm odor preventatives, and oral hygiene products (mouthwash, toothpaste, mouth fresheners, gargles, etc.). The composition can be prepared by conventional methods by appropriately combining carriers that are acceptable as cosmetics, etc. (for example, diluents, dispersants, buffers, pH adjusters, emulsifiers, surfactants, preservatives, stabilizers, antioxidants, colorants, humectants, thickeners, disinfectants, fragrances, etc.).

[0031] A virus inactivation composition used in the gas phase (for example, a spatial virus inactivation composition) can be prepared by blending (A) maleic acrylate copolymer or a salt thereof and (B) a surfactant, as well as a base and various additives (polyols (dipropylene glycol, propylene glycol, etc.), surfactants other than component (B), UV absorbers, antioxidants, preservatives, deodorants, natural extracts, silicones, thickeners, dyes, pigments, colorants, oils, fragrances, etc.). Such a composition may take the form of a liquid or a gel, but a liquid form is preferred.

[0032] In this specification, examples of bases include conventionally known substances, whether oily or aqueous, such as water, methanol, ethanol, propanol, isopropanol, butanol, isobutanol, 3-methyl-3-methoxybutanol, propylene glycol, triethylene glycol, dimethyl ether, liquid propane, petrolatum, lanolin, castor oil, and paraffinic hydrocarbons (e.g., liquid paraffin). These bases can be used individually or in combination of two or more. Furthermore, when the virus inactivation composition is to be prepared as a gel, it can be prepared by appropriately adding a natural gelling agent or a synthetic gelling agent, such as a water-soluble gelling agent like carrageenan or gellan gum, or an oil-soluble gelling agent like metal soap or aluminum octylate, according to conventionally known methods.

[0033] The content of the active ingredient in the embodiment in which the virus inactivating agent of the present invention is used as a composition can be appropriately determined depending on the form of the composition. For example, the content of (A) maleic acrylate copolymer or its salt relative to the total amount of the composition is preferably 0.001% by mass or more, more preferably 0.01% by mass or more, and even more preferably 0.5% by mass or more. There is no particular upper limit, for example, preferably 99.99% by mass or less, and even more preferably 10% by mass or less. Furthermore, the content of surfactant (B) relative to the total amount of the composition is preferably 0.005% by mass or more, more preferably 0.1% by mass or more. There is no particular upper limit, but it is preferably 90% by mass or less, and even more preferably 50% by mass or less.

[0034] In the present invention, the ratio of the combination of (A) maleic acrylate copolymer or a salt thereof and (B) surfactant is preferably 0.5 parts by mass or more, more preferably 5 parts by mass or more, and even more preferably 50 parts by mass or more, of (B) surfactant per 1 part by mass of (A) maleic acrylate copolymer or a salt thereof, from the viewpoint of virus inactivation effect.

[0035] The virus inactivator in the present invention is active under acidic, neutral, and alkaline conditions. However, from the viewpoint of safety and virus inactivation effect, the pH (at 20°C) of the composition in which the virus inactivator is used as a composition is preferably 3 to 11, more preferably 3 to 5 or 10 to 11. The pH shall be measured using a pH meter after adjusting the temperature to 20°C. The virus inactivator in the present invention has high activity under alkaline conditions, and the pH (at 20°C) of the composition in which the virus inactivator is used as a composition, or when applied, is preferably 8 to 12, more preferably 9 to 11, and more preferably 10 to 11. In the present invention, the virus inactivating agent is preferably a composition in which the virus inactivating agent is used, or the pH (at 20°C) at the time of application is preferably between pH 5 and 8, from the viewpoint of application to neutral detergents, tolerance for the incorporation of general-purpose ingredients, and achieving both a mild feel and low reactivity to the skin and application object, and a high virus inactivation effect.

[0036] The virus inactivator of the present invention makes it possible to inactivate viruses in objects where viral contamination is a concern. Objects where viral contamination is a concern to which (A) acrylic acid maleic acid copolymer or a salt thereof and (B) surfactant, or compositions containing these, can be applied include, for example, the skin or mucous membranes of animals to which viruses adhere, hard or soft surfaces of inanimate objects, objects such as waste, and living spaces where viruses are airborne or dispersed. Here, examples of surfaces of inanimate objects include hard surfaces in homes and business facilities such as counters, sinks, restrooms, toilets, bathtubs, showers, floors, windows, doorknobs, walls, drains, pipes, and garbage collection areas; hard surfaces of special vehicles such as garbage trucks and sanitation vehicles such as garbage inlets, work surfaces, and switch surfaces; hard surfaces of transport vehicles such as railway cars and aircraft bodies such as floors, handrails, and door surfaces; hard surfaces of various appliances, tools, and miscellaneous goods such as kitchenware, furniture, telephones, and toys; and soft surfaces of textile products (carpets, area rugs, curtains, seats, fabric furniture, clothing, masks, etc.). Examples of waste include general waste (household waste such as food scraps, tissues, and masks) and industrial waste (sludge, human waste, medical waste, etc.). If the waste is contained within a bag, the bag surface may be targeted. Other examples of living spaces include the entrance hall, dining kitchen, bedroom, children's room, bathroom, toilet, etc. within ordinary homes; the interiors of facilities such as shops, restaurants, inns, hospitals, workshops, factories, garbage collection points, quarantine stations, livestock farms, and markets; the interiors of vehicles such as cars, trains, and airplanes; and semi-enclosed spaces (lockers, storage rooms, closets, etc.; storage boxes (for toys, karaoke microphones, dishes, condiments, writing instruments, stationery)).

[0037] In the virus inactivator of the present invention, (A) maleic acrylate copolymer or a salt thereof and (B) a surfactant, or a composition containing these, are applied to objects where viral contamination is a concern, but the embodiment is not particularly limited, and (A) maleic acrylate copolymer or a salt thereof and (B) a surfactant may be brought into contact with or reacted with the virus in a liquid phase or a gas phase. The method for bringing (A) maleic acrylate copolymer or a salt thereof and (B) a surfactant into contact with the virus in a liquid phase may be any of the following: applying (A) maleic acrylate copolymer or a salt thereof and (B) a surfactant, or a composition containing these, directly to the object to be treated; diffusing (A) maleic acrylate copolymer or a salt thereof and (B) a surfactant, or a composition containing these, onto the object to be treated; or wiping the surface of the object with a sheet, gauze, towel, wet wipe, tissue, wet wipe, etc., impregnated with (A) maleic acrylate copolymer or a salt thereof and (B) a surfactant, or a composition containing these. Another method involves filling a known spray container, such as a trigger spray container (direct pressure or pressurized type), a dispenser-type pump spray container, or an aerosol spray container equipped with a pressure-resistant vessel, with (A) maleic acrylic acid copolymer or a salt thereof and (B) a surfactant, or a composition containing these, and spraying it onto the target object while appropriately adjusting the spray volume. Another method involves filling an atomizing device such as a pressurized air atomizing sprayer, nebulizer, or diffuser, or a diffusion device such as a washer nozzle or misting machine, and spraying it into a space where the virus is present. By spraying it in a mist form into a space where the virus is present, the volatilization rate can be increased, and the virus inactivation effect can be rapidly exerted.

[0038] A method for contacting or reacting (A) maleic acrylate copolymer or a salt thereof with (B) a surfactant with a virus in the gas phase includes, for example, a form in which (A) maleic acrylate copolymer or a salt thereof with (B) a surfactant is allowed to volatilize naturally or by forced volatilization. This can inactivate viruses present in living spaces and allow for easy removal of viruses from the air (virus removal). When the virus inactivator in the present invention is used for the purpose of natural volatilization, conventionally known methods can be applied, such as impregnating a core rod, filter paper, etc., with (A) maleic acrylate copolymer or a salt thereof and (B) a surfactant, or a composition containing these, and allowing it to volatilize, or using a permeable membrane for volatilization. Alternatively, (A) maleic acrylate copolymer or a salt thereof and (B) a surfactant, or a composition containing these, can be kneaded into a resin and used. Examples of resins that can be kneaded include natural, petroleum-based, and synthetic waxes, rosin resins, ethylene-vinyl acetate copolymers, ethylene-vinyl alcohol copolymers, polyesters, polyolefins, and acrylic resins. The above kneaded material can be used as is, or it can be supported on a porous carrier, made into a sheet, or used as a laminate of the sheet. Examples of porous carriers include natural polymers such as cellulose and chitosan, the above synthetic resins, and inorganic porous materials such as calcium silicate, which can be made into granules, sheets, or any other shape. The above-mentioned mixtures and laminates can be used, for example, by installing them in air conditioning equipment, toilets, bathrooms, living rooms, hospital rooms, waiting rooms, dustbins, etc., while gradually volatilizing (A) maleic acrylate copolymer or its salt and (B) surfactant. Alternatively, (A) maleic acrylate copolymer or its salt and (B) surfactant, or compositions containing these, can be supported on products made of paper, nonwoven fabric, etc. (such as air purifier filters) and used. When (A) acrylic acid maleic acid copolymer or a salt thereof and (B) a surfactant are used by forced volatilization, such means include, for example, a method of volatilization using a fan, a heating volatilization method using a heater, and a method of volatilization using ultrasound. When performing airborne virus removal treatment, the amount of (A) acrylic acid maleic acid copolymer or its salt and (B) surfactant, or composition containing these, can be appropriately adjusted depending on the treatment method, the ambient environment such as temperature and humidity, the vapor pressure of the compound, etc. It is also possible to set the concentration above the saturation concentration of the compound in the space. For example, the concentration of (A) acrylic acid maleic acid copolymer or its salt, or (B) surfactant in the target space should be 0.1% by mass or more, preferably 1% by mass or more, more preferably 5% by mass or more, even more preferably 10% by mass or more, preferably 100% by mass or less, preferably 50% by mass or less, more preferably 25% by mass or less, and even more preferably 20% by mass or less, before volatilizing. The concentration of (A) acrylic acid maleic acid copolymer or its salt, or (B) surfactant, in the target space can be detected by measuring the concentration of the compound in a gas sample taken from the space. Methods for determining the concentration include using a volatile organic compound (VOC) concentration meter (VOC meter, odor sensor, etc.), or using gas chromatography or gas chromatography / mass spectrometry in combination with a gas collection tube, etc.

[0039] With regard to the embodiments described above, the present invention further discloses the following aspects.

[0040] <1> A virus inactivator comprising (A) maleic acrylate copolymer or a salt thereof, and (B) at least one surfactant selected from anionic surfactants, cationic surfactants, and amphoteric surfactants as active ingredients. <2> A method for inactivating a virus, comprising applying (A) a maleic acrylate copolymer or a salt thereof, and (B) at least one surfactant selected from anionic surfactants, cationic surfactants, and amphoteric surfactants, or a composition containing the same, to an object suspected of being contaminated by a virus. <3> A virus inactivation composition comprising (A) maleic acrylate copolymer or a salt thereof, and (B) at least one surfactant selected from anionic surfactants, cationic surfactants, and amphoteric surfactants as active ingredients, The composition contains 0.01% by mass or more and 10% by mass or less, and the mass ratio of component (A) to component (B) [(B) / (A)] is 0.03 or more and 250 or less. A virus inactivating composition for application to objects suspected of viral contamination, which is diluted with water to form a diluted solution containing component (A) at a concentration of 10 ppm to 1000 ppm. <4> A virus inactivation composition comprising (A) maleic acrylate copolymer or a salt thereof, and (B) at least one surfactant selected from anionic surfactants, cationic surfactants, and amphoteric surfactants as active ingredients, A virus inactivating composition in which the concentration of component (A) in the composition is 10 ppm or more and 1000 ppm or less, and the mass ratio of component (A) to component (B) [(B) / (A)] is 0.03 or more and 250 or less.

[0041] <5> The molar ratio (acrylic acid:maleic acid) of acrylic acid-derived constituent units to maleic acid-derived constituent units constituting the acrylic acid-maleic acid copolymer or its salt is preferably 0.20:0.80 to 0.80:0.20. <1> ~ <4> A virus inactivating agent, a virus inactivation method, or a virus inactivation composition as described in any of the above. <6> The surfactant is preferably at least one surfactant selected from alkyl sulfates, alkylbenzene sulfonates, internal olefin sulfonates having 10 to 18 carbon atoms, polyoxyalkylene alkyl ether sulfates, polyoxyalkylene alkenyl ether sulfates and polyoxyalkylene alkylaryl ether sulfates, fatty acid salts, pyrophosphates, lauryl phosphate, polycarboxylic acid type polymers, polyoxyethylene alkylene alkyl acetates, aromatic sulfonate formalin condensates, polyoxyethylene distyrenated ether sulfates, alkyldiphenyl ether disulfonates, dialkyl sulfosuccinates and alkylnaphthalene sulfonates. <1> ~ <5> A virus inactivating agent, a virus inactivation method, or a virus inactivation composition as described in any of the above. <7> The surfactant is preferably at least one surfactant selected from alkylbenzyldimethylammonium salts, dialkyldimethylammonium salts, alkyltrimethylammonium salts, and triethanolamine diester quaternary salts. <1> ~ <5> A virus inactivating agent, a virus inactivation method, or a virus inactivation composition as described in any of the above. <8> The surfactant is preferably at least one surfactant selected from alkylcarbobetaine, alkyl(amidopropyl)carbobetaine, alkylsulfobetaine, alkyl(amidopropyl)sulfobetaine, alkylhydroxysulfobetaine, and alkyldimethylamine oxide. <1> ~ <5> A virus inactivating agent, a virus inactivation method, or a virus inactivation composition as described in any of the above. <9> The surfactant is preferably at least one surfactant selected from alkyl sulfate salts, alkylbenzene sulfonates, internal olefin sulfonates having 10 to 18 carbon atoms, polyoxyethylene alkyl ether sulfate salts, fatty acid salts, alkyldimethylamine oxide, alkylhydroxysulfobetaine, and alkylbenzyldimethylammonium salts. <1> ~ <5> A virus inactivating agent, a virus inactivation method, or a virus inactivation composition as described in any of the above. <10> The virus is preferably an RNA virus that does not have an envelope, and more preferably a norovirus. <1> ~ <9> A virus inactivating agent, a virus inactivation method, or a virus inactivation composition as described in any of the above. <11> Preferably used in a liquid phase state. <1> ~ <10> A virus inactivating agent, a virus inactivation method, or a virus inactivation composition as described in any of the above. <12> The pH of the composition is preferably 3 to 11, more preferably 3 to 5 or 10 to 11. <2> ~ <11> A method for inactivating a virus or a virus inactivation composition as described in any of the above. [Examples]

[0042] Test Example 1: Evaluation against Feline Calicivirus (FCV) To achieve the concentrations and pH shown in Tables 1-9, use the acrylic acid / maleic acid copolymers and methyl vinyl ether / maleic acid copolymers (product names: Gantrez S-96 BF Solution ST, Gantrez S-97 BF, manufactured by Ashland Japan), sodium dodecylbenzenesulfonate (product name: Neoperex G-65, manufactured by Kao), and ammonium lauryl sulfate (product name: Emal). AD-25 (manufactured by Kao Corporation), potassium C16 internal olefin sulfonate obtained by reference to the method described in Japanese Patent Publication No. 2021-88702 (manufactured by Kao Corporation), sodium polyoxyethylene (EO=2) alkyl (R=10-16) ether sulfate (manufactured by Kao Corporation), lauryl dimethylamine oxide (product name: Anhitol 20N, manufactured by Kao Corporation), lauryl hydroxysulfobetaine (product name: Anhitol 20HD, manufactured by Kao Corporation), alkylbenzyldimethylammonium chloride (product name: Sanizol B-50, manufactured by Kao Corporation), sodium dialkyl sulfosuccinate (product name: Perex OT-P, manufactured by Kao Corporation), ammonium polyoxyalkylene alkenyl ether sulfate (product name: Latemul PD-104, manufactured by Kao Corporation), ammonium polyoxyethylene distyrenated ether sulfate (product name: Latemul E-1000A, manufactured by Kao Corporation), oleic acid (product name: Lunac OV (manufactured by Kao Corporation) was suspended in sterile deionized water or various pH standard solutions (Fujifilm Wako Pure Chemical Industries). Neutral phosphate pH standard solution (Fujifilm Wako Pure Chemical Industries) was used to prepare test solutions for pH 3-4 and pH 5.2-7, sterile deionized water was used to prepare the pH 5 test solution, and carbonate pH standard solution (Fujifilm Wako Pure Chemical Industries) was used to prepare the pH 9-10 test solutions. Furthermore, the pH of the pH 5 test solution was adjusted with 1% by mass citric acid and 1M potassium hydroxide solution, while the pH of test solutions other than pH 5 was adjusted with 2M hydrochloric acid solution and 1M potassium hydroxide solution. Aqueous solutions adjusted to the pH shown in the table using the aforementioned acid, alkali, pH standard solution, and sterile deionized water were used as controls. These controls did not contain polymers or surfactants. The units in the table are "mass%". The pH and pfu / mL after mixing the test solution and feline calicivirus solution are shown in the table. The inactivation effect of the test solution on feline calicivirus (FCV) was evaluated using the method described below.

[0043] <Evaluation Method> The inactivation evaluation of viruses was performed with reference to the "FY2015 Survey Report on Norovirus Inactivation Conditions" (National Institute of Health Sciences) and ASTM-E1052, which are generally known as standard methods for evaluating virus inactivation. First, feline calicivirus solutions (F-9 strain, ATCC VR-782) with log pfu / mL values ​​of approximately 8, 6, and 6.3, respectively, were prepared. The virus solutions with log pfu / mL values ​​of approximately 8 and 6 were used in the tests shown in Table 6 and Table 3, respectively. The virus solution with log pfu / mL value of approximately 6.3 was used in tests other than those shown in Table 6 and Table 3. 90 μL of each test solution shown in the table and 10 μL of the above-mentioned feline calicivirus solution were placed in a 1.5 mL sample tube and mixed thoroughly. After reacting at 30°C for the time indicated in the table, the reaction was stopped by diluting 10-fold with 900 μL of quenching solution (SCDLP solution). The solution after reaction stoppage was serially diluted 10-fold, 100-fold, and 1000-fold in DMEM medium. 0.5 mL of each of these dilutions was used to infect CRFK cells (feline kidney-derived cell line) (ATCC CCL-94) washed with PBS (phosphate-buffered saline), and after 1 hour, the medium was replaced with methylcellulose-containing medium. After culturing at 37°C for 2 days, the cells were stained with crystal violet and the number of plaques was counted.

[0044] [Table 1]

[0045] [Table 2]

[0046] [Table 3]

[0047] [Table 4]

[0048] [Table 5]

[0049] [Table 6]

[0050] [Table 7]

[0051] [Table 8]

[0052] [Table 9]

[0053] Test Example 2: Evaluation against human norovirus (HNV) To achieve the concentrations and pH values ​​shown in Tables 10-11, the acrylic acid / maleic acid copolymers, ammonium lauryl sulfate (product name: Emal AD-25, manufactured by Kao Corporation), sodium dodecylbenzenesulfonate (product name: Neoperex G-65, manufactured by Kao Corporation), and lauryldimethylamine oxide (product name: Anhithol 20N, manufactured by Kao Corporation) were suspended in the respective pH standard solutions (manufactured by Fujifilm Wako Pure Chemical Industries). Neutral phosphate pH standard solutions were used to prepare test solutions with pH values ​​from 3 to 5.5, and carbonate pH standard solutions were used to prepare the test solution with pH 10. pH adjustment was performed using 2M hydrochloric acid solution and 1M potassium hydroxide solution. The pH standard solutions adjusted to the pH values ​​shown in the tables were used as controls. The units in the tables are "mass%". The pH values ​​shown in the tables are the pH after mixing the test solution and virus solution. The HNV (HuNoV) inactivation effect was evaluated using the method described below.

[0054] <Evaluation Method> (1) Culture of human intestinal epithelial organoids (hIEOs) hIEOs were embedded in Matrigel (Corning) on ​​24-well plates and then cultured in three dimensions under conditions of 37°C and 5% CO2. IntestiCult Organoid Growth Medium (Human) (STEMCELL Technologies) was used as the culture medium. The entire volume of medium (500 μL / 2 days) was changed every 2-3 days, and subculturing was performed every 5-7 days. After 3D culture, the hIEOs were suspended in TrypLE Express (Thermo Fisher Scientific) along with the Matrigel. The hIEOs were dispersed by enzymatic treatment at 37°C for 10 minutes, and to stop the reaction, a basal medium containing Advanced DMEM / F-12 (Gibco) supplemented with 100 U / mL Penicillin-Streptomycin (Thermo Fisher Scientific), 10 mM HEPES (Thermo Fisher Scientific), and 1×GlutaMAX (Thermo Fisher Scientific) was added. After settling the cells by centrifugation (3 minutes, 300×g, 4°C), the above medium was removed. Cells were suspended in differentiation medium supplemented with 1×B27 supplement (Thermo Fisher Scientific), 10nM gastrin I (Sigma-Aldrich), 1mM N-acetylcysteine ​​(Fujifilm Wako), 50ng / mL mouse EGF recombinant protein (Thermo Fisher Scientific), 100ng / mL mouse Noggin (Peprotech), 500μg / mL human R-spondin-1 (R&D Systems), 500nM A83-01 (Tocris), and 10μM Y-27632 (Fujifilm Wako) in basal medium. Furthermore, for monolayer culture, 96-well flat-bottom plates coated with Cell Matrix (registered trademark) type IC (Nitta Gelatin) were prepared. To prepare the plates, 100 μL of Cell Matrix type IC (Nitta Gelatin), diluted 10-fold with 0.1 M acetic acid (Nacalai tesque), was added to each well, and then incubated at 37°C for 90 minutes. After that, the solution was removed and washed three times with 200 μL of D-PBS(-) (Nacalai tesque). 5 × 10⁶ cells were added to the 96-well flat-bottom plates that had undergone the above treatment. 4 Cells were seeded at a concentration of 100 μL / well. Differentiation induction was carried out for a total of 6 days, with the entire differentiation medium being replaced every 2 days, to obtain monolayered hIEOs.

[0055] (2) Preparation of a 10% emulsion of feces containing HNV (HuNoV) A 10% fecal emulsion was prepared from the feces of patients with HNV type GII.4. One tablet of the protease inhibitor cOmplete protease inhibitor cocktail tablets (Sigma-Aldrich, 11697498001) was suspended in 50 mL of D-PBS(-). 1 g of feces was suspended in 10 mL of cOmplete-containing D-PBS(-) and thoroughly mixed using a test tube mixer. After standing at 4°C for 20 minutes, the mixture was centrifuged at 2,000 × g at 4°C for 10 minutes. The supernatant was collected in a new tube and stored at -80°C until use in infection experiments.

[0056] (3) Inactivation treatment of HNV and infection of differentiated hIEOs A 10% fecal emulsion containing HNV was diluted 10-fold with differentiation medium and filtered using a 1 mL syringe and a Millex HV Filter unit (Millipore, SLHVR04NL). 5 μL of the filtered fecal solution (2.8 × 10⁶) was collected in a PA microcentrifuge tube (Beckman coulter). 6A 45 μL test solution containing HNV genome copy equivalent and polymers of the specified concentrations shown in Tables 10-11 was mixed and reacted at the specified temperatures and times shown in Tables 10-11. Next, 0.95 mL of Fetal Bovine Serum (Capricorn Scientific) solution was added to this drug-treated fecal solution. The centrifuge tube was set on a fixed-angle rotor TLA-55 (Beckman coulter) and ultracentrifuged for 1.5 hours at Rmax with a centrifugal force of 186047 × g (equivalent to 55,000 rpm) using an Optima MAX-TL (Beckman coulter), and the supernatant was removed. The pellet was suspended in 100 μL of differentiation medium to prepare the infection solution for hIEOs. After removing the existing medium from the wells (96-well plate), the infection solution prepared in the above manner was applied to the hIEOs after 6 days of differentiation induction. Incubation was performed at 37°C for 1 hour. After washing three times with 300 μL of basal medium, 250 μL of differentiation medium was added, and the cells were cultured at 37°C under 5% CO2 conditions until sampling. 10 μL of supernatant was collected immediately after the start of culture and again after 6 days of culture. The collected supernatant was centrifuged at 15,000 rpm for 5 minutes to remove cell debris, and then frozen and stored at -80°C until HuNoV genome RNA quantification was performed.

[0057] (4) RT-qPCR The number of HNV genome copies in the recovered supernatant was quantified using the Norovirus Detection Kit G1 / G2 (Toyobo, FIK-273). The procedure followed the protocol. PCR amplification and data measurement were performed using LightCycler480II (Roche).

[0058] [Table 10]

[0059] [Table 11]

Claims

1. A virus inactivator comprising (A) maleic acrylate copolymer or a salt thereof, and (B) at least one surfactant selected from anionic surfactants, cationic surfactants, and amphoteric surfactants as active ingredients.

2. The virus inactivator according to claim 1, wherein component (B) surfactant is at least one surfactant selected from anionic surfactants and amphoteric surfactants.

3. The virus inactivator according to claim 1 or 2, wherein the virus is an RNA virus that does not have an envelope.

4. The virus inactivator according to claim 1 or 2, wherein the virus is norovirus.

5. The virus inactivator according to claim 1 or 2, wherein the concentration of component (A) is 10 ppm or more and 1000 ppm or less, and the mass ratio of component (A) to component (B) [(B) / (A)] is 0.03 or more and 250 or less.

6. A method for inactivating a virus, comprising applying (A) a maleic acrylate copolymer or a salt thereof, and (B) at least one surfactant selected from anionic surfactants, cationic surfactants, and amphoteric surfactants, or a composition containing the same, to an object suspected of being contaminated by a virus.

7. A virus inactivation composition comprising (A) maleic acrylate copolymer or a salt thereof, and (B) at least one surfactant selected from anionic surfactants, cationic surfactants, and amphoteric surfactants as active ingredients, The content of component (A) in the composition is 0.01% by mass or more and 10% by mass or less, and the mass ratio of component (A) to component (B) [(B) / (A)] is 0.03 or more and 250 or less. A virus inactivation composition for application to objects suspected of viral contamination, which is diluted with water to form a diluted solution containing 10 ppm to 1000 ppm of component (A) and applied to the object.

8. A virus inactivation composition comprising (A) maleic acrylate copolymer or a salt thereof, and (B) at least one surfactant selected from anionic surfactants, cationic surfactants, and amphoteric surfactants as active ingredients, A virus inactivating composition in which the concentration of component (A) in the composition is 10 ppm or more and 1000 ppm or less, and the mass ratio of component (A) to component (B) [(B) / (A)] is 0.03 or more and 250 or less.

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