WO2021256540A1 - Virus-inactivating preparation - Google Patents

Virus-inactivating preparation Download PDF

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Publication number
WO2021256540A1
WO2021256540A1 PCT/JP2021/023059 JP2021023059W WO2021256540A1 WO 2021256540 A1 WO2021256540 A1 WO 2021256540A1 JP 2021023059 W JP2021023059 W JP 2021023059W WO 2021256540 A1 WO2021256540 A1 WO 2021256540A1
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WIPO (PCT)
Prior art keywords
virus
test
fumaric acid
acid
inactivating agent
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PCT/JP2021/023059
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French (fr)
Japanese (ja)
Inventor
一彦 奥薗
繁 土居
Original Assignee
第一製網株式会社
西日本長瀬株式会社
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Priority to JP2021561857A priority Critical patent/JP7509380B2/en
Publication of WO2021256540A1 publication Critical patent/WO2021256540A1/en

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    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N25/00—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests
    • A01N25/30—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests characterised by the surfactants
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N31/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic oxygen or sulfur compounds
    • A01N31/02—Acyclic compounds
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N37/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids
    • A01N37/06—Unsaturated carboxylic acids or thio analogues thereof; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01P—BIOCIDAL, PEST REPELLANT, PEST ATTRACTANT OR PLANT GROWTH REGULATORY ACTIVITY OF CHEMICAL COMPOUNDS OR PREPARATIONS
    • A01P1/00—Disinfectants; Antimicrobial compounds or mixtures thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
    • A61K31/225—Polycarboxylic acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/12—Carboxylic acids; Salts or anhydrides thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/22—Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/42—Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A61P31/16—Antivirals for RNA viruses for influenza or rhinoviruses

Definitions

  • the present invention relates to a virus inactivating preparation such as influenza virus, norovirus, and new coronavirus (SARS-CoV2).
  • virus inactivating preparation such as influenza virus, norovirus, and new coronavirus (SARS-CoV2).
  • viruses include enveloped viruses (eg, influenza virus, coronavirus [including new coronavirus (SARS-CoV2)], RS virus, SARS virus, etc.) and non-enveloped non-enveloped virus (eg, influenza virus, SARS virus, etc.).
  • enveloped viruses eg, influenza virus, coronavirus [including new coronavirus (SARS-CoV2)], RS virus, SARS virus, etc.
  • non-enveloped non-enveloped virus eg, influenza virus, SARS virus, etc.
  • adenovirus, norovirus, rotavirus, enterovirus, etc. are present.
  • Norovirus is an non-enveloped RNA virus (hereinafter referred to as "norovirus") classified into Caliciviridae and Norovirus genus, and is alcohol (ethanol, isopropanol, etc.), heat, acidic (stomach acid, etc.), Alternatively, it has a strong resistance to drying and the like.
  • the incubation period is thought to be 1 to 2 days, and the main symptoms of nausea, vomiting, and diarrhea appear, but may be accompanied by abdominal pain, headache, fever, chills, muscle pain, sore throat, and malaise.
  • Oral infection is known as one of the infection routes of norovirus, etc., and infection is established by ingesting food, water, etc. contaminated with norovirus, etc. Therefore, in places such as restaurants, school lunch facilities, and factories where food is cooked and processed, it is required to prevent food, water, and the like from being contaminated by norovirus and the like.
  • a method for inactivating a virus such as norovirus for example, a method using a chlorine bleach (sodium hypochlorite or the like) is known, but the chlorine bleach has a corrosive effect on metals. It has an irritating effect on the skin and a bleaching effect on clothing. Therefore, there is a drawback that its use is restricted, and in particular, it is not appropriate to use these chemicals on the hands, tableware, countertops, cooking utensils, etc. of workers in consideration of safety for the human body. It was not appropriate to let them come into direct contact with food. Therefore, agents and methods that are safe for the human body and can inactivate norovirus and the like have been desired.
  • a chlorine bleach sodium hypochlorite or the like
  • FCV feline calicivirus
  • MNV murine norovirus
  • influenza is an acute respiratory infection caused by the influenza virus, and different types of influenza are prevalent all over the world every year.
  • influenza virus infection is prevented by vaccination or treated with drugs such as neuraminidase inhibitors, but there is a problem that their effects differ significantly depending on the type of influenza virus. ..
  • drugs have problems such as side effects and the emergence of resistant viruses.
  • safe and secure influenza virus inactivating agents that are less harmful to the human body, such as those contained in foods and drinks, are eagerly desired. ing.
  • an inactivating agent or the like that can inactivate the above-mentioned virus, for example, 1) (A) 35 to 75% by mass of lower alcohol, (B) (b1) organic acid and its alkali metal salt, and / or (b2) inorganic acid and its alkali metal salt 0.05 to 10% by mass. (C) Contains 0.05 to 5% by mass of at least one nonionic surfactant selected from monoglycerin fatty acid ester, polyglycerin fatty acid ester, sorbitan fatty acid ester, polyoxyethylene sorbitan fatty acid ester, and sucrose fatty acid ester.
  • A) ethanol 50-70% by weight of (A) ethanol, and (B) organic acids (apple acid, lactic acid, citric acid, tartaric acid, salicylic acid, gluconic acid, adipic acid, phytic acid, acetic acid, fumaric acid, succinic acid, At least one selected from the group consisting of ascorbic acid, sorbic acid, benzoic acid, propionic acid, and maleic acid), at least one selected from the group consisting of (these) organic acid salts and ethanolamines.
  • a disinfectant solution for norovirus and the like which contains 0.05 to 4.50% by weight and has a pH of 6 to 12, and further contains 0.20 to 0.30% by weight of (C) glycerin fatty acid ester.
  • Disinfectant (see, for example, Patent Document 2), 3) Contact a composition consisting of an aqueous solution containing ethanol and acid as an active ingredient and having a pH in the range of 2.5 to 5.0 with a substance containing suspected calicivirus and a protein.
  • a method for inactivating feline calicivirus in the presence of a protein (see, for example, Patent Document 3). 4) (a) The ethanol concentration is 65 to 75% by weight, (b) the content of glycerin fatty acid ester is 0.03 to 0.15% by weight, and (c) the content of lactic acid or a salt thereof is 1.
  • Agents for viruses, antibacterial and antifungal agents see, eg, Patent Document 4), 5)
  • malic acid, lactic acid, phosphoric acid, tartaric acid, adipic acid is at least one selected from the group consisting of succinic acid, and phytic acid, the type of the cation and the anion, K + and SO 4 2-of combination, Fe 2+ and SO 4 2-combinations of, Cu 2+ and SO 4 2-combinations of, K + and Al 3+ and SO 4 2-combinations of, NH 4 + and Al 3+ and SO 4 2-a combination of, Na + and NO 3 - in combination, NH 4 + and NO 3 - in combination, Na + and NO 2 - in combination, K + and NO 2 - in combination, NH 4 + and NO 2 - combination of, Na + and SCN - combination, or, Na + and I - viral inactivating agent which is a combination of (e.g., see Patent Document 5), 6) A virus inactivating agent containing ethanol, a carbonate (at least one selected from the group consisting of sodium carbonate, potassium carbonate and ammonium carbon
  • Patent Documents 1 to 6 disclose the proximity technique of the present invention in that ethanol, various acids and the like are used, but these are technical ideas (configuration and its peculiarity) with the present invention in the following points and the like. The action and effect) are different.
  • 35 to 75% by mass of ethanol (95% of the amount of active ingredient treated as a dangerous substance) as a lower alcohol and 0.05 to 10 of citric acid or a salt thereof as an organic acid are used.
  • a bactericidal disinfectant composition containing% by mass, monoglycerin fatty acid ester, polyglycerin fatty acid ester, etc., and the pH (25 ° C.) of the undiluted solution of the composition is set in the range of 8 to 12 in the high alcohol range. It is a product, does not use fumaric acid used in the present invention, has a high concentration of ethanol, and has an alkaline pH, so that there are problems such as rough hands.
  • Patent Document 2 there is a description that 50 to 70% by weight of ethanol and fumaric acid can be used in combination as an organic acid, but there is no support for the examples, and there is a description that fumaric acid alone can inactivate the virus.
  • Patent Documents 3 to 6 contain a combination of ethanol and an acid (citric acid, lactic acid, etc.), and further contain a carbonate, a cation, an anion, etc. in each predetermined concentration range. There is no description or suggestion of, and the technical idea is different from that of the present invention.
  • ethanol has been used as rubbing alcohol or the like, and as described in each of the above patent documents, it has been used in combination with other components, but when the alcohol concentration is 60% by mass or more, in Japan. It falls under the category of dangerous goods stipulated in the Fire Service Act, and it is necessary to be careful in its handling, and when storing and handling a certain amount or more, notification and application are required.
  • fumaric acid is used as an acidulant for food additives and has a very strong bactericidal activity among organic acids, so it is used for cleaning foods (vegetables, etc.) and sterilizing and cleaning tank lines of food factories.
  • fumaric acid itself can be inactivated against influenza virus, norovirus, and the new coronavirus (SARS-CoV2).
  • Japanese Unexamined Patent Publication No. 2009-173641 Japanese Unexamined Patent Publication No. 2014-19659 (Claims, Examples, etc.) Japanese Unexamined Patent Publication No. 2014-129372 (Claims, Examples, etc.) JP-A-2019-73453 (Claims, Examples, etc.) JP-A-2019-156810 (Claims, Examples, etc.) JP-A-2019-182761 (Claims, Examples, etc.)
  • the present invention is intended to solve the above-mentioned problems of the prior art and the current situation, and is excellent in handleability, odorless, safe and efficient, influenza virus, norovirus, and new coronavirus (SARS-CoV2). It is an object of the present invention to provide a virus inactivating preparation capable of realizing the inactivation of).
  • the present inventors have selected fumaric acid as an influenza virus, norovirus, and new coronavirus (SARS-CoV2) among the organic acids used as acidulants for foods.
  • SARS-CoV2 new coronavirus
  • the virus inactivating preparation of the above object could be obtained, and the virus inactivating preparation of the present invention was completed. That is, in the first invention of the present invention, the virus inactivating preparation is characterized by containing fumaric acid as a main component, and in the second invention, it is characterized by containing fumaric acid and ethanol.
  • the content of the fumaric acid is preferably 0.005 to 1% by mass, and the content of the ethanol is preferably 50% by mass or less.
  • the pH of the virus inactivating agent is preferably 2.0 to 5.5.
  • the virus inactivating agent preferably contains at least one selected from glycerin fatty acid ester, polyglycerin fatty acid ester, xanthan gum, sodium benzoate, potassium sorbate, polylysine, dehydroacetic acid and sodium dehydroacetate.
  • the virus inactivating agent it is preferable that the virus that can be inactivated is influenza virus, feline calicivirus, and new coronavirus (SARS-CoV2).
  • a virus inactivating preparation that is easy to handle, is odorless, and can safely and efficiently inactivate influenza virus, norovirus, and new coronavirus (SARS-CoV2).
  • SARS-CoV2 new coronavirus
  • the virus-inactivated preparation of the present invention is characterized in that it contains fumaric acid as a main component in the first invention, and is characterized in that it contains fumaric acid and ethanol in the second invention. be.
  • the fumaric acid used is not particularly limited, but is preferably a volume average particle diameter of 30 ⁇ m or less, more preferably 15 ⁇ m or less, and particularly preferably 10 ⁇ m or less, and the fumaric acid commercially available as a raw material is pulverized by a dry or wet method. Then, the one having the above-mentioned preferable particle size is used. Further, it may be used that has been crystallized and taken out so as to have a preferable particle size at the time of raw material production.
  • the content of fumaric acid used is 0.005 to 1% by mass (hereinafter, “mass%” is simply referred to as “%”), more preferably 0.03 to 1% by mass, based on the total amount of the virus-inactivated preparation. It is desirable to set it to 0.6%. If the content of fumaric acid is less than 0.005%, the effect of the present invention may not be exhibited, while if it exceeds 1%, the solubility is not sufficient, which is not preferable.
  • the fumaric acid alone acts as an inactivating component against influenza virus and norovirus (substitute for feline calicivirus), but further, in terms of product stability and storage stability. Therefore, fumaric acid and ethanol can be used in combination.
  • the content of fumaric acid is the same as in the case of the above-mentioned fumaric acid alone (0.005 to 1%, preferably 0.01 to 0.6%) with respect to the total amount of the virus-inactivated preparation.
  • the ethanol content is preferably 50% or less, more preferably 5 to 40%, and particularly preferably 10 to 40%.
  • the pH of the virus-inactivated preparations of the first invention and the second invention is preferably 2.0 to 5.5, more preferably 2.2 to 4.0, from the viewpoint of antiviral effect. Is desirable.
  • the pH range (2.0 to 5.5) is adjusted by adjusting the content of fumaric acid, and when ethanol is used in combination, the content of ethanol is adjusted to further adjust the remaining water (remaining water (). It can be adjusted by the content of tap water, distilled water, ion-exchanged water, purified water, pure water, ultra-pure water, etc. It can be adjusted by adding it.
  • the virus inactivating preparations of the first invention and the second invention are preferably glycerin fatty acid ester, polyglycerin fatty acid ester, xanthan gum, from the viewpoint of solubilization, product stability, and antifungal effect. It preferably contains at least one selected from sodium benzoate, potassium sorbate, polylysine, dehydroacetic acid and sodium dehydroacetate. These ingredients are used as food additives, and their safety has been confirmed.
  • glycerin fatty acid ester The above-mentioned glycerin fatty acid ester, polyglycerin fatty acid ester, and xanthan gum take into consideration the poor solubility of fumaric acid (solubility in water: 25 ° C., 0.63 g / 100 mL), and disperse performance and dispersion stability in virus-inactivated preparations.
  • the total content is preferably 0.001 to 20%, more preferably 0.003 to 17.5%, based on the total amount of the virus-inactivating preparation. Is desirable.
  • an aqueous dispersion in which fumaric acid having a predetermined volume average particle size is dispersed in advance with the glycerin fatty acid ester, polyglycerin fatty acid ester, the dispersion stabilizer of xanthan gum or the like is used. It is preferable, and particularly preferably, the above-mentioned predetermined amount of fumaric acid having a volume average particle size of 10 ⁇ m or less, xanthan gum 0.01 to 5%, and glycerin fatty acid ester 0.025 to 12.5% with respect to the total amount of the composition.
  • an aqueous dispersion of fumaric acid containing the above-mentioned water is desirable to use an aqueous dispersion of fumaric acid containing the above-mentioned water as a balance.
  • the above-mentioned predetermined amount of fumaric acid having a volume average particle diameter of 10 ⁇ m or less the above-mentioned predetermined amount of ethanol, xanthan gum 0.01 to 5%, and glycerin fatty acid ester 0. It is desirable to use an aqueous dispersion of ethanol fumarate containing 025 to 12.5% and the balance of the above water.
  • the above-mentioned sodium benzoate, potassium sorbate, polylysine, dehydroacetic acid and sodium dehydroacetate are preservatives used in foods and cosmetics, and fumaric acid can be added by containing these components as necessary. It is possible to further realize antifungal measures and storage stability when used alone, and the total content is preferably 0.01 to 5%, more preferably 0.1, based on the total amount of the virus-inactivated preparation. It is desirable to set it to ⁇ 2%.
  • the virus inactivating preparations of the first invention and the second invention of the present invention configured in this way are excellent in handleability, and safely and efficiently inactivate influenza virus, norovirus, and new coronavirus (SARS-CoV2). realizable.
  • the virus inactivating agent of the present invention includes food factories, coffee shops, restaurants, hotels, taverns, school meals, central kitchens, kitchen tables such as supermarket backyards, hospitals / nursing facilities, and spaces, refrigerators, and storages of these facilities.
  • the virus inactivating agent of the present invention includes fibers such as masks, towels, sheets, cloths, tablecloths, curtains, white clothes, and clothing, or floorboards, tatami mats, walls, folds, chairs, tables, doors, kitchen equipment, etc.
  • a virus inactivating agent aqueous fumaric acid solution
  • spraying it and then drying it to fix fumaric acid and apply anti-virus processing.
  • a binder having a predetermined concentration such as acrylic, polyurethane or polyester can be used in combination (blended) with the virus inactivating agent.
  • fumaric acid is used as an acidulant for foods, and at the applied concentration, it has almost no acidity and is odorless, colorless and transparent, and can be applied to fresh products such as agricultural and marine products, and to the oral cavity, nasal cavity, and skin.
  • the method of using the virus inactivating agent is not particularly limited, but for example, the object is immersed in the virus inactivating agent, and the virus inactivating agent is applied or sprayed on the object (for example, trigger spray, dispenser spray, aerosol, etc.). , It may be naturally dried as it is, or it can be used by air-drying, wiping, etc.
  • the amount to be applied or sprayed on the object may be any amount as long as it can be applied or sprayed evenly on the object, and the amount is not particularly limited, but is, for example, about 1 to 20 mL.
  • the virus inactivating agent of the present invention can be impregnated into a non-woven fabric to form a virus inactivating material, and the virus can be efficiently inactivated by wiping it as a wet sheet.
  • Test Example 1 Examples 1 and 2
  • a virus inactivation test evaluation was performed by the following test method.
  • the pH values of the test samples 1 and 2 were measured using a pH meter HM-30G (manufactured by Toa DKK Corporation) at a liquid temperature of 25 ° C. (the same was also measured for Test Examples 2 and later described later).
  • test sample 1 (total amount 100%): Fumaric acid (volume average particle size is 10 ⁇ m, the same applies below) 0.3% Xanthan gum 0.002% Glycerin fatty acid ester 0.005% Water (purified water) 99.693% pH value 2.3
  • Composition of test sample 2 (total amount 100%): Fumaric acid 0.3% 50% ethanol Xanthan gum 0.002% Glycerin fatty acid ester 0.005% Water (purified water) 49.693% pH value 2.3
  • test samples 1 and 2 prepared above, antiviral test, specifically, 0.9 ml of each test sample solution and 0.1 ml of the test virus solution are mixed with the following test virus for 30 minutes (5 minutes). Let it stand still. Then, 9 ml of SCDLP was added to prepare a 10-fold diluted series, and the viral infectious titer after the action was determined by the plaque method. The smaller this number, the smaller the viral load.
  • Test virus 1 Feline calicivirus F-9 strain (feline calicivirus, ATCC VR-782) Host cell: CRFK cell (ATCC CCL-94)
  • Test virus 2 Influenza A virus (H3N2) A / Hong Kong / 8/68 strain (influenza A virus, ATCC VR-1679)
  • Host cell MDCK cell (ATCC CCL-34)
  • Test Examples 2 to 6 Next, in Test Examples 2 to 6 below, a virus inactivation test by comparing fumaric acid with other organic acids (citrate, lactic acid), a virus inactivation test by changing the concentration of fumaric acid, and fumaric acid and ethanol. A virus inactivation test by combined use, a virus inactivation test by changing the action time of fumaric acid, and a virus inactivation test against the new corona virus (SARS-CoV2) (the above antiviral activity value was calculated) were performed. If the concentration of fumaric acid or the like is the same in each sample solution, the description of the pH value will be omitted hereafter.
  • SARS-CoV2 new corona virus
  • Test Example 2 Example 3 and Comparative Examples 1 and 2
  • an antiviral test specifically, 0.9 ml of each test sample solution and 0.1 ml of the test virus solution are mixed with the following test virus and allowed to stand for 30 minutes. Then, 9 ml of SCDLP was added to prepare a 10-fold diluted series, and the virus infectivity value after the action was determined by the plaque method, and the antiviral activity value was determined.
  • Test virus Feline calicivirus F-9 strain (feline calicivirus, ATCC VR-782)
  • Host cell CRFK cell (ATCC CCL-94)
  • Test Example 3 Examples 4 to 6 and Comparative Example 3
  • an antiviral test specifically, 0.9 ml of each test sample solution and 0.1 ml of the test virus solution are mixed with the following test virus and allowed to stand for 30 minutes. Then, 9 ml of SCDLP was added to prepare a 10-fold diluted series, and the virus infectivity value after the action was determined by the plaque method, and the antiviral activity value was determined.
  • Test virus Influenza A virus (H3N2) A / Hong Kong / 8/68 strain (Influenza A virus, ATCC VR-1679)
  • Host cell MDCK cell (ATCC CCL-34)
  • Test Example 4 Examples 7 to 9
  • an antiviral test specifically, 0.9 ml of each test sample solution and 0.1 ml of the test virus solution are mixed with the following test virus and allowed to stand for 5 minutes. Then, 9 ml of SCDLP was added to prepare a 10-fold diluted series, and the virus infectivity value after the action was determined by the plaque method, and the antiviral activity value was determined.
  • Test virus Influenza A virus (H3N2) A / Hong Kong / 8/68 strain (influenza A virus, ATCC VR-1679) Host cell: MDCK cell (ATCC CCL-34) Test virus: Feline calicivirus F-9 strain (feline calicivirus, ATCC VR-782) Host cell: CRFK cell (ATCC CCL-94)
  • Test Example 5 Examples 10 to 17
  • the anti-virus test specifically 0.9 ml of each test sample solution and 0.1 ml of the test virus solution, were mixed with the test viruses shown in Tables 5 and 6 below for a certain period of time (15 seconds, 30 seconds, 60 seconds, 30 minutes) Let stand. Then, 9 ml of SCDLP was added to prepare a 10-fold diluted series, and the virus infectivity value after the action was determined by the plaque method, and the antiviral activity value was determined. These results are shown in Tables 5 and 6 below.
  • Test virus Influenza A virus (H3N2) A / Hong Kong / 8/68 strain (influenza A virus, ATCC VR-1679) Host cell: MDCK cell (ATCC CCL-34) Test virus: Feline calicivirus F-9 strain (feline calicivirus, ATCC VR-782) Host cell: CRFK cell (ATCC CCL-94)
  • Test Example 6 Examples 18 to 19
  • the effect on the new coronavirus (SARS-CoV-2) was tested by the following test method.
  • Test method 1) Add 10 ⁇ l of the virus solution to 90 ⁇ l of the solution having the composition shown in Table 7 below. 2) Let stand for 1 minute at room temperature. 3) Take 10 ⁇ l and suspend in 1000 ⁇ l cell culture medium (1/100 dilution). 4) Using a 96-well plate, serially dilute (TCID50 method) 5) After 3 days, the TCID50 value is measured and the viral load is calculated.
  • Virus name SARS-CoV-2 Virus strain name: JPN / TY / WK-521
  • GISAID EPI_ISL_408667 Reference: Matsuyama S et al., PNAS 2020, 117: 7001-7003 * Cultured cell line: VeroE6 / TMPRSS2 Culture medium: DMEM low Glc 10% FCS These results are shown in Table 7 below.
  • Example 20 The effect of fumaric acid-processed dough on influenza virus was tested by the following test method.
  • the polyester fabric manufactured by Color Dyeing Co., Ltd.
  • the polyester fabric is immersed in a 0.3% fumaric acid solution, squeezed (squeezing ratio 110 to 115%), blown and dried at 80 ° C., and adhered as shown in Table 8 below.
  • An amount of fumaric acid processed PET dough was prepared.
  • An antiviral test for influenza virus was carried out using this fumaric acid-processed dough.
  • the test method [Compliant with JIS L 1922 (ISO 18184)] is shown below.
  • Test method 1. 1. Inoculate each test product with the test virus solution (standard 200 ⁇ l / test product) Let stand at 2.25 ° C for 2 hours. (Control samples "immediately after inoculation" should be collected immediately without standing.) 3. 3. Add 20 ml of SCDLP medium to neutralize and recover the virus. 4. Create a 10-fold serial dilution series. 5. The prepared host cells are inoculated with the recovered stock solution and the diluted solution, respectively. After 6.1 hours, the agar medium is layered. After culturing for 7.4 days, the cells are fixed, agar is removed, and then staining is performed. 8. Visually measure the number of plaques to determine the infectious titer of the virus. 9.
  • Test virus Influenza A virus (H3N2) A / Hong Kong / 8/68 strain (influenza A virus, ATCC VR-1679)
  • Test Example 8 Example 21
  • the effect of fumaric acid-processed dough on feline calicivirus was tested.
  • the polyester fabric (color dyeing company Co., Ltd.) is immersed in a 0.6% fumaric acid solution, squeezed (squeezing ratio 110 to 115%), blown and dried at 80 ° C., and the fumaric acid shown in Table 6 below is used.
  • a processed PET fabric was created.
  • An antiviral test was carried out using a fumaric acid-processed dough, and an antiviral activity value was determined.
  • Feline calicivirus was used as the test virus, and the antiviral test was carried out in the same manner as in Test Example 7 above. These results are shown in Table 9 below.
  • Test virus Feline calicivirus F-9 strain (feline calicivirus, ATCC VR-782)
  • Test Example 9 Examples 22 to 26
  • the antiviral effect (combined with a binder) of the fumaric acid-processed dough was tested.
  • the fumaric acid + binder-processed polyester fabric (color dyeing company Co., Ltd.) shown in Table 7 above was prepared and evaluated for its antiviral effect.
  • Feline calicivirus was used as the test virus, and the antiviral test was carried out in the same manner as in Test Example 7 above. These results are shown in Table 10 below.
  • Test virus Influenza A virus (H3N2) A / Hong Kong / 8/68 strain (influenza A virus, ATCC VR-1679)
  • Staphylococcus aureus (Staphylococcus) A test was performed using aureus NBRC12732). The test method is based on "JIS L 1902: 2008 (ISO 20743), bacterial solution absorption method", and the washing method is based on "JIS L 0217, 103", using the following two types of dough. It was carried out by a quantitative test (calculation of antibacterial activity value) by the liquid absorption method. Fumaric acid-0.1% processed PET dough and fumaric acid-0.1% + mobile 963-3% processed PET dough were tested. The results are shown in Table 11 below. The antibacterial activity value A is evaluated as "an antibacterial effect is recognized" when 2.0 ⁇ A ⁇ 3.0 and "a strong effect is observed" when 3.0 ⁇ A.
  • the virus inactivating agent according to the present invention is norovirus, influenza virus, and new corona. It was confirmed that it had an inactivating effect on the virus (SARS-CoV2), and that it had a high anti-virus effect even in a short working time of 15 seconds. Considering the results of Test Examples 7 to 9 above, it was confirmed that both fumaric acid alone and the combined use of the binder had an antiviral activity value of 4.4 and had a high antiviral effect. It was found that the merit of using the above binder in combination is that the same effect can be exhibited even if the concentration of fumaric acid is lowered, and that it is a preferable embodiment even when washing resistance or the like is required.
  • a virus inactivating preparation that is easy to handle, odorless, and can safely and efficiently inactivate influenza virus, norovirus, and new coronavirus (SARS-CoV2) can be obtained.

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Abstract

Provided is a virus-inactivating preparation for inactivating influenza virus, feline calicivirus (norovirus), novel coronavirus (SARS-CoV2) and the like.　A virus-inactivating preparation according to the present invention is characterized by containing fumaric acid as the main component, or is characterized by containing ethanol and fumaric acid.

Description

ウイルス不活化製剤Virus inactivated drug
　本発明は、インフルエンザウイルス、ノロウイルス、新型コロナウイルス（SARS-CoV2）などのウイルス不活化製剤に関する。 The present invention relates to a virus inactivating preparation such as influenza virus, norovirus, and new coronavirus (SARS-CoV2).
　一般に、ウイルスには、エンベロープを有するエンベロープウイルス（例えば、インフルエンザウイルス、コロナウイルス〔新型コロナウイルス（SARS-CoV2）を含む〕、ＲＳウイルス、ＳＡＲＳウイルス等）や、エンベロープを有さないノンエンベロープウイルス（例えば、アデノウイルス、ノロウイルス、ロタウイルス、エンテロウイルス等）が存在している。 Generally, viruses include enveloped viruses (eg, influenza virus, coronavirus [including new coronavirus (SARS-CoV2)], RS virus, SARS virus, etc.) and non-enveloped non-enveloped virus (eg, influenza virus, SARS virus, etc.). For example, adenovirus, norovirus, rotavirus, enterovirus, etc.) are present.
　これらのウイルスの中には、ヒトに感染するものもあり、感染予防のために従来からウイルス不活性化剤が用いられていた。
　近年、ノロウイルス（ヒトノロウイルス）による感染性胃腸炎あるいは食中毒の発生が一年を通じて多発しており、特に１１～３月が発生のピークとなっている。ノロウイルスは、カリシウイルス科、ノロウイルス属に分類されるエンベロープを有さないＲＮＡウイルス（以下、「ノロウイルス等」と記載する）であり、アルコール（エタノール、イソプロパノール等）、熱、酸性（胃酸等）、又は、乾燥等に対して強い抵抗力を有する。潜伏期間は１～２日であると考えられており、嘔気、嘔吐、下痢の主症状が出るが、腹痛、頭痛、発熱、悪寒、筋痛、咽頭痛、倦怠感等を伴うこともある。 Some of these viruses infect humans, and virus inactivating agents have been conventionally used to prevent infection.
In recent years, outbreaks of infectious gastroenteritis or food poisoning due to norovirus (human norovirus) have frequently occurred throughout the year, and the peak of the outbreak is from November to March. Norovirus is an non-enveloped RNA virus (hereinafter referred to as "norovirus") classified into Caliciviridae and Norovirus genus, and is alcohol (ethanol, isopropanol, etc.), heat, acidic (stomach acid, etc.), Alternatively, it has a strong resistance to drying and the like. The incubation period is thought to be 1 to 2 days, and the main symptoms of nausea, vomiting, and diarrhea appear, but may be accompanied by abdominal pain, headache, fever, chills, muscle pain, sore throat, and malaise.
　ノロウイルス等の感染経路の一つとして経口感染が知られており、ノロウイルス等に汚染された食物や水等を経口摂取することにより感染が成立する。そのため、飲食店、給食施設、工場など食品を調理加工する場においては、食物や水等がノロウイルス等に汚染されないようにすることが求められている。 Oral infection is known as one of the infection routes of norovirus, etc., and infection is established by ingesting food, water, etc. contaminated with norovirus, etc. Therefore, in places such as restaurants, school lunch facilities, and factories where food is cooked and processed, it is required to prevent food, water, and the like from being contaminated by norovirus and the like.
　上記ノロウイルス等のウイルスを不活性化させる方法等としては、例えば、塩素系漂白剤（次亜塩素酸ナトリウム等）を用いる方法が知られているが、塩素系漂白剤は、金属に対する腐食作用、皮膚等に対する刺激作用、衣類に対する漂白作用等がある。そのため、その使用が制限されるという欠点があり、特に、人体に対する安全性への配慮から作業者の手指、食器、調理台、調理器具等にこれらの薬剤類を用いることは適当とはいえず、まして食物に直接触れさせることも適当とはいえなかった。そのため、人体に対し安全であり、ノロウイルス等を不活性化できる剤や方法が望まれていた。なお、ヒトノロウイルスは、培養細胞を用いても増殖させることができない。そのため、ヒトノロウイルスの不活性化に対する各種消毒剤等の消毒効果などの検証には、代替ウイルスとしてネコカリシウイルス（ＦＣＶ）やマウスノロウイルス（ＭＮＶ）が広く用いられている。ＦＣＶ及びＭＮＶは、形態的特徴やゲノムの構造から、ヒトノロウイルスに近縁なウイルスであることが明らかにされている。 As a method for inactivating a virus such as norovirus, for example, a method using a chlorine bleach (sodium hypochlorite or the like) is known, but the chlorine bleach has a corrosive effect on metals. It has an irritating effect on the skin and a bleaching effect on clothing. Therefore, there is a drawback that its use is restricted, and in particular, it is not appropriate to use these chemicals on the hands, tableware, countertops, cooking utensils, etc. of workers in consideration of safety for the human body. It was not appropriate to let them come into direct contact with food. Therefore, agents and methods that are safe for the human body and can inactivate norovirus and the like have been desired. It should be noted that human norovirus cannot be propagated even by using cultured cells. Therefore, feline calicivirus (FCV) and murine norovirus (MNV) are widely used as alternative viruses for verifying the disinfecting effect of various disinfectants and the like on the inactivation of human norovirus. FCV and MNV have been clarified as viruses closely related to human norovirus from their morphological characteristics and genomic structure.
　一方、インフルエンザは、インフルエンザウイルスを病原体とする急性の呼吸器感染症であり、毎年違う型のインフルエンザが世界中で流行している。一般的に、インフルエンザウイルスの感染に対しては、ワクチン接種による予防や、ノイラミニダーゼ阻害剤等の薬剤による治療が行われているが、インフルエンザウイルスのタイプによってはそれらの効果が著しく異なるという問題がある。また、薬剤によっては副作用や耐性ウイルスの出現といった問題も残されている。このような問題に鑑み、インフルエンザウイルスの予防・治療に効果のある物質の探索においては、飲食品に配合されるような、人体に害の少ない安全・安心なインフルエンザウイルス不活化剤等が切望されている。 On the other hand, influenza is an acute respiratory infection caused by the influenza virus, and different types of influenza are prevalent all over the world every year. In general, influenza virus infection is prevented by vaccination or treated with drugs such as neuraminidase inhibitors, but there is a problem that their effects differ significantly depending on the type of influenza virus. .. In addition, some drugs have problems such as side effects and the emergence of resistant viruses. In view of these problems, in the search for substances that are effective in the prevention and treatment of influenza virus, safe and secure influenza virus inactivating agents that are less harmful to the human body, such as those contained in foods and drinks, are eagerly desired. ing.
　従来において、上記のウイルスに対して、不活性化できる不活性化剤等としては、例えば、
１）　（Ａ）低級アルコール３５～７５質量％と、（Ｂ）（ｂ１）有機酸およびそのアルカリ金属塩、および／または（ｂ２）無機酸およびそのアルカリ金属塩０．０５～１０質量％と、（Ｃ）モノグリセリン脂肪酸エステル、ポリグリセリン脂肪酸エステル、ソルビタン脂肪酸エステル、ポリオキシエチレンソルビタン脂肪酸エステル、ショ糖脂肪酸エステルから選ばれる少なくとも一種の非イオン界面活性剤０．０５～５質量％とを含有するとともに、（Ｄ）成分として水を含有し、且つ組成物の原液のｐＨ（ＪＩＳ　Ｚ－８８０２：１９８４「ｐＨ測定方法」）が、２５℃で８～１２の範囲に設定されていることを特徴とする殺菌消毒剤組成物（例えば、特許文献１参照）
２）　（Ａ）エタノールを５０～７０重量％、並びに、（Ｂ）有機酸（リンゴ酸、乳酸、クエン酸、酒石酸、サリチル酸、グルコン酸、アジピン酸、フィチン酸、酢酸、フマル酸、コハク酸、アスコルビン酸、ソルビン酸、安息香酸、プロピオン酸、及び、マレイン酸からなる群から選ばれた少なくとも１種）、（これらの）有機酸塩及びエタノールアミン類からなる群から選ばれた少なくとも１種を０．０５～４．５０重量％含み、ｐＨが６～１２であることを特徴とする、ノロウイルス用などの消毒液、さらに、（Ｃ）グリセリン脂肪酸エステルを０．２０～０．３０重量％含む消毒液（例えば、特許文献２参照）、
３）　カリシウイルスの存在が疑われ、かつタンパク質を含有する物に、有効成分としてエタノールと酸を含み、pHが２．５～５．０の範囲にある水溶液からなる組成物を接触させることを含む、タンパク質共存下のカリシウイルスを不活化する方法（例えば、特許文献３参照）、
４）　（ａ）エタノール濃度が６５～７５重量％、（ｂ）グリセリン脂肪酸エステルの含有量が０．０３～０．１５重量％、（ｃ）乳酸またはその塩の含有量が、乳酸として１．０～１．８重量％、（ｄ）クエン酸またはその塩の含有量が、クエン酸として０．２～０．５重量％、（ｅ）ｐＨ３～４であることを満たす水溶液である、抗ウイルス、抗細菌および抗真菌用の薬剤（例えば、特許文献４参照）、
５）　水と、エタノール８．０５～８５．７０重量％と、陽イオンと、陰イオンと、酸剤とを含む水溶液状のウイルス不活性化剤であって、前記酸剤は、クエン酸、リンゴ酸、乳酸、リン酸、酒石酸、アジピン酸、コハク酸及びフィチン酸からなる群から選択される少なくとも１種であり、前記陽イオン及び前記陰イオンの種類は、Ｋ＋及びＳＯ４ ２－の組み合わせ、Ｆｅ２＋及びＳＯ４ ２－の組み合わせ、Ｃｕ２＋及びＳＯ４ ２－の組み合わせ、Ｋ＋及びＡｌ３＋並びにＳＯ４ ２－の組み合わせ、ＮＨ４ ＋及びＡｌ３＋並びにＳＯ４ ２－の組み合わせ、Ｎａ＋及びＮＯ３ －の組み合わせ、ＮＨ４ ＋及びＮＯ３ －の組み合わせ、Ｎａ＋及びＮＯ２ －の組み合わせ、Ｋ＋及びＮＯ２ －の組み合わせ、ＮＨ４ ＋及びＮＯ２ －の組み合わせ、Ｎａ＋及びＳＣＮ－の組み合わせ、又は、Ｎａ＋及びＩ－の組み合わせであることを特徴とするウイルス不活性化剤（例えば、特許文献５参照）、
６）　エタノールと、炭酸塩（炭酸ナトリウム、炭酸カリウム及び炭酸アンモニウムからなる群から選択される少なくとも１種）と、酸剤とを含むウイルス不活性化剤であって、前記ウイルス不活性化剤中の前記炭酸塩の質量濃度は、０．１０重量％を超えて、８．００重量％未満であることを特徴とするウイルス不活性化剤（例えば、特許文献６参照）、などが知られている。 Conventionally, as an inactivating agent or the like that can inactivate the above-mentioned virus, for example,
1) (A) 35 to 75% by mass of lower alcohol, (B) (b1) organic acid and its alkali metal salt, and / or (b2) inorganic acid and its alkali metal salt 0.05 to 10% by mass. (C) Contains 0.05 to 5% by mass of at least one nonionic surfactant selected from monoglycerin fatty acid ester, polyglycerin fatty acid ester, sorbitan fatty acid ester, polyoxyethylene sorbitan fatty acid ester, and sucrose fatty acid ester. At the same time, it is characterized in that it contains water as a component (D) and the pH of the undiluted solution of the composition (JIS Z-8802: 1984 "pH measuring method") is set in the range of 8 to 12 at 25 ° C. Ester disinfectant composition (see, for example, Patent Document 1).
2) 50-70% by weight of (A) ethanol, and (B) organic acids (apple acid, lactic acid, citric acid, tartaric acid, salicylic acid, gluconic acid, adipic acid, phytic acid, acetic acid, fumaric acid, succinic acid, At least one selected from the group consisting of ascorbic acid, sorbic acid, benzoic acid, propionic acid, and maleic acid), at least one selected from the group consisting of (these) organic acid salts and ethanolamines. A disinfectant solution for norovirus and the like, which contains 0.05 to 4.50% by weight and has a pH of 6 to 12, and further contains 0.20 to 0.30% by weight of (C) glycerin fatty acid ester. Disinfectant (see, for example, Patent Document 2),
3) Contact a composition consisting of an aqueous solution containing ethanol and acid as an active ingredient and having a pH in the range of 2.5 to 5.0 with a substance containing suspected calicivirus and a protein. A method for inactivating feline calicivirus in the presence of a protein (see, for example, Patent Document 3).
4) (a) The ethanol concentration is 65 to 75% by weight, (b) the content of glycerin fatty acid ester is 0.03 to 0.15% by weight, and (c) the content of lactic acid or a salt thereof is 1. An aqueous solution satisfying that the content of (d) citric acid or a salt thereof is 0 to 1.8% by weight, 0.2 to 0.5% by weight of citric acid, and (e) pH 3 to 4. Agents for viruses, antibacterial and antifungal agents (see, eg, Patent Document 4),
5) An aqueous virus inactivating agent containing water, 8.05 to 85.70% by weight of ethanol, cations, anions, and an acid agent, wherein the acid agent is citric acid. malic acid, lactic acid, phosphoric acid, tartaric acid, adipic acid is at least one selected from the group consisting of succinic acid, and phytic acid, the type of the cation and the anion, K + and SO 4 2-of combination, Fe 2+ and SO 4 2-combinations of, Cu 2+ and SO 4 2-combinations of, K + and Al 3+ and SO 4 2-combinations of, NH 4 + and Al 3+ and SO 4 2-a combination of, Na + and NO 3 - in combination, NH 4 + and NO 3 - in combination, Na + and NO 2 - in combination, K + and NO 2 - in combination, NH 4 + and NO 2 - combination of, Na + and SCN - combination, or, Na + and I - viral inactivating agent which is a combination of (e.g., see Patent Document 5),
6) A virus inactivating agent containing ethanol, a carbonate (at least one selected from the group consisting of sodium carbonate, potassium carbonate and ammonium carbonate) and an acid agent, which is contained in the virus inactivating agent. A virus inactivating agent (see, for example, Patent Document 6) characterized in that the mass concentration of the carbonate is more than 0.10% by weight and less than 8.00% by weight is known. There is.
　上記特許文献１～６は、エタノールや各種酸などを用いる点で、本発明の近接技術を開示するものであるが、これらは下記の点等で本発明とは技術思想（構成及びその特有の作用効果）等が相違するものである。
　上記特許文献１の実施例等には、低級アルコールとして、エタノール（危険物として取り扱われる有効成分量９５％）３５～７５質量％と、有機酸としてクエン酸やその塩等を０．０５～１０質量％と、モノグリセリン脂肪酸エステル、ポリグリセリン脂肪酸エステルなどを含有するとともに、且つ組成物の原液のｐＨ（２５℃）が、高アルカリ域の８～１２の範囲に設定されている殺菌消毒剤組成物であり、本発明で用いるフマル酸を用いるものでなく、また、エタノールの濃度も高く、かつ、ｐＨもアルカリ域のため、手荒れ等が生じやすいなどの課題があるものである。
　上記特許文献２では、エタノールを５０～７０重量％と、有機酸としてフマル酸を併用できる記載があるが実施例のサポートはなく、しかも、フマル酸単独でウイルスの不活性化できることについての記載や示唆乃至実証はなされていないものであり、また、リンゴ酸、その塩などを用いた実施例１～４及び比較例１～２を考察すると、ｐＨが酸性域（４．０、４．２）では消毒効果がないものである。
　上記特許文献３～６は、エタノールと酸（クエン酸、乳酸等）との併用、更に、炭酸塩や陽イオン・陰イオンなどを各所定の濃度範囲でそれぞれ含有するものであるが、フマル酸の記載や示唆はないものであり、本発明とは技術思想が相違するものである。 The above-mentioned Patent Documents 1 to 6 disclose the proximity technique of the present invention in that ethanol, various acids and the like are used, but these are technical ideas (configuration and its peculiarity) with the present invention in the following points and the like. The action and effect) are different.
In the examples of Patent Document 1, 35 to 75% by mass of ethanol (95% of the amount of active ingredient treated as a dangerous substance) as a lower alcohol and 0.05 to 10 of citric acid or a salt thereof as an organic acid are used. A bactericidal disinfectant composition containing% by mass, monoglycerin fatty acid ester, polyglycerin fatty acid ester, etc., and the pH (25 ° C.) of the undiluted solution of the composition is set in the range of 8 to 12 in the high alcohol range. It is a product, does not use fumaric acid used in the present invention, has a high concentration of ethanol, and has an alkaline pH, so that there are problems such as rough hands.
In the above Patent Document 2, there is a description that 50 to 70% by weight of ethanol and fumaric acid can be used in combination as an organic acid, but there is no support for the examples, and there is a description that fumaric acid alone can inactivate the virus. No suggestion or proof has been made, and when Examples 1 to 4 and Comparative Examples 1 to 2 using malic acid, a salt thereof, etc. are considered, the pH is in the acidic range (4.0, 4.2). There is no disinfecting effect.
The above-mentioned Patent Documents 3 to 6 contain a combination of ethanol and an acid (citric acid, lactic acid, etc.), and further contain a carbonate, a cation, an anion, etc. in each predetermined concentration range. There is no description or suggestion of, and the technical idea is different from that of the present invention.
　なお、従来より、エタノールを消毒用アルコール等として、また、上記各特許文献に記載されるように、他の各成分などと併用されているが、アルコール濃度が６０質量％以上では、日本国では消防法に定める危険物に該当し、その取り扱いに注意する必要があり、また、一定以上の量を貯蔵・取り扱う場合には届出・申請が必要となるものである。
　また、フマル酸は、食品添加物の酸味料として使用されており、有機酸の中でも殺菌力が非常に強いため、食品（野菜など）の洗浄や食品工場のタンク・ライン等の殺菌洗浄などに使用されているものであるが、フマル酸自体がインフルエンザウイルス、ノロウイルス、新型コロナウイルス（SARS-CoV2）に対して不活化できることは今まで知られていなかった。 Conventionally, ethanol has been used as rubbing alcohol or the like, and as described in each of the above patent documents, it has been used in combination with other components, but when the alcohol concentration is 60% by mass or more, in Japan. It falls under the category of dangerous goods stipulated in the Fire Service Act, and it is necessary to be careful in its handling, and when storing and handling a certain amount or more, notification and application are required.
In addition, fumaric acid is used as an acidulant for food additives and has a very strong bactericidal activity among organic acids, so it is used for cleaning foods (vegetables, etc.) and sterilizing and cleaning tank lines of food factories. Although used, it has not been known that fumaric acid itself can be inactivated against influenza virus, norovirus, and the new coronavirus (SARS-CoV2).
特開２００９－１７３６４１号公報（特許請求の範囲、実施例等）Japanese Unexamined Patent Publication No. 2009-173641 (Claims, Examples, etc.) 特開２０１４－　１９６５９号公報（特許請求の範囲、実施例等）Japanese Unexamined Patent Publication No. 2014-19659 (Claims, Examples, etc.) 特開２０１４－１２９３７２号公報（特許請求の範囲、実施例等）Japanese Unexamined Patent Publication No. 2014-129372 (Claims, Examples, etc.) 特開２０１９－　７３４５３号公報（特許請求の範囲、実施例等）JP-A-2019-73453 (Claims, Examples, etc.) 特開２０１９－１５６８１０号公報（特許請求の範囲、実施例等）JP-A-2019-156810 (Claims, Examples, etc.) 特開２０１９－１８２７６１号公報（特許請求の範囲、実施例等）JP-A-2019-182761 (Claims, Examples, etc.)
　本発明は、上記従来技術の課題及び現状などに鑑み、これを解消しようとするものであり、取り扱い性に優れ、無臭であり、安全かつ効率よくインフルエンザウイルス、ノロウイルス、新型コロナウイルス（SARS-CoV2）の不活化を実現できるウイルス不活化製剤を提供することを目的とする。 The present invention is intended to solve the above-mentioned problems of the prior art and the current situation, and is excellent in handleability, odorless, safe and efficient, influenza virus, norovirus, and new coronavirus (SARS-CoV2). It is an object of the present invention to provide a virus inactivating preparation capable of realizing the inactivation of).
　本発明者らは、上記従来の課題等について、鋭意検討した結果、食品の酸味料として使用されている有機酸の中で、フマル酸をインフルエンザウイルス、ノロウイルス、新型コロナウイルス（SARS-CoV2）のウイルス不活化に利用できないかを検討・実証試験などを施したところ、上記目的のウイルス不活化製剤が得られることを見出し、本発明のウイルス不活化製剤を完成するに至ったのである。
　すなわち、本発明の第１発明では、ウイルス不活化製剤は、フマル酸を主成分とすることを特徴とし、また、第２発明では、フマル酸とエタノールとを含有することを特徴とする。
　前記フマル酸の含有量は０．００５～１質量％であることが好ましく、また、前記エタノールの含有量は５０質量％以下であることが好ましい。
　前記ウイルス不活化剤のｐＨが２．０～５．５であることが好ましい。
　前記ウイルス不活化剤には、グリセリン脂肪酸エステル、ポリグリセリン脂肪酸エステル、キサンタンガム、安息香酸ナトリウム、ソルビン酸カリウム、ポリリジン、デヒドロ酢酸及びデヒドロ酢酸ナトリウムから選ばれる少なくとも１種を含有することが好ましい。
　前記ウイルス不活化剤は、不活化できるウイルスがインフルエンザウイルス、ネコカリシウイルス、新型コロナウイルス（SARS-CoV2）であることが好ましい。 As a result of diligent studies on the above-mentioned conventional problems, the present inventors have selected fumaric acid as an influenza virus, norovirus, and new coronavirus (SARS-CoV2) among the organic acids used as acidulants for foods. As a result of examining whether it can be used for virus inactivation and conducting verification tests, it was found that the virus inactivating preparation of the above object could be obtained, and the virus inactivating preparation of the present invention was completed.
That is, in the first invention of the present invention, the virus inactivating preparation is characterized by containing fumaric acid as a main component, and in the second invention, it is characterized by containing fumaric acid and ethanol.
The content of the fumaric acid is preferably 0.005 to 1% by mass, and the content of the ethanol is preferably 50% by mass or less.
The pH of the virus inactivating agent is preferably 2.0 to 5.5.
The virus inactivating agent preferably contains at least one selected from glycerin fatty acid ester, polyglycerin fatty acid ester, xanthan gum, sodium benzoate, potassium sorbate, polylysine, dehydroacetic acid and sodium dehydroacetate.
As the virus inactivating agent, it is preferable that the virus that can be inactivated is influenza virus, feline calicivirus, and new coronavirus (SARS-CoV2).
　本発明によれば、取り扱い性に優れ、無臭であり、安全かつ効率よくインフルエンザウイルス、ノロウイルス、新型コロナウイルス（SARS-CoV2）の不活化を実現できるウイルス不活化製剤が提供される。
　本発明の目的及び効果は、特に請求項において指摘される構成要素及び組み合わせを用いることによって認識され且つ得られるものである。本明細書における前述の一般的な説明及び後述の詳細な説明の両方は、例示的及び説明的なものであり、特許請求の範囲に記載されている本発明を制限するものではない。 According to the present invention, there is provided a virus inactivating preparation that is easy to handle, is odorless, and can safely and efficiently inactivate influenza virus, norovirus, and new coronavirus (SARS-CoV2).
The objects and effects of the present invention are recognized and obtained in particular by using the components and combinations pointed out in the claims. Both the general description described above and the detailed description below are illustrative and descriptive herein and are not intended to limit the invention described in the claims.
　以下に、本発明の実施形態を詳しく説明する。但し、本発明の技術的範囲は、下記で詳述するそれぞれの実施の形態に限定されず、特許請求の範囲に記載された発明とその均等物に及ぶ点に留意されたい。
　本発明のウイルス不活化製剤は、第１発明ではフマル酸を主成分とすることを特徴とするものであり、また、第２発明ではフマル酸とエタノールとを含有することを特徴とするものである。 Hereinafter, embodiments of the present invention will be described in detail. However, it should be noted that the technical scope of the present invention is not limited to the respective embodiments detailed below, but extends to the inventions described in the claims and their equivalents.
The virus-inactivated preparation of the present invention is characterized in that it contains fumaric acid as a main component in the first invention, and is characterized in that it contains fumaric acid and ethanol in the second invention. be.
　用いるフマル酸は、インフルエンザウイルス（エンベロープウイルス）、ノロウイルス（ノンエンベロープウイルス）、新型コロナウイルス（SARS-CoV2）のウイルス不活化成分として使用するものであり、構造式〔ＨＯＯＣ－ＣＨ＝ＣＨ－ＣＯＯＨ（トランス体）〕で表され、水難溶性の結晶性の粉末である。
　用いるフマル酸は、特に限定されないが、好ましくは、体積平均粒子径３０μｍ以下、より好ましくは１５μｍ以下、特に好ましくは１０μｍ以下であり、原料として市販されているフマル酸を乾式又は湿式の方法で粉砕して上記好ましい粒径のものを使用する。また、原料製造時に好ましい粒径になるよう結晶化させて取り出したものを使用しても良い。 The fumaric acid used is used as a virus inactivating component of influenza virus (enveloped virus), norovirus (non-enveloped virus), and new corona virus (SARS-CoV2), and has a structural formula [HOOC-CH = CH-COOH (HOOC-CH = CH-COOH). It is a crystalline powder that is sparingly soluble in water and is represented by trans form)].
The fumaric acid used is not particularly limited, but is preferably a volume average particle diameter of 30 μm or less, more preferably 15 μm or less, and particularly preferably 10 μm or less, and the fumaric acid commercially available as a raw material is pulverized by a dry or wet method. Then, the one having the above-mentioned preferable particle size is used. Further, it may be used that has been crystallized and taken out so as to have a preferable particle size at the time of raw material production.
　用いるフマル酸の含有量は、ウイルス不活化製剤全量に対して、０．００５～１質量％（以下において、「質量％」を単に「％」として表記する）、更に好ましくは、０．０３～０．６％とすることが望ましい。
　このフマル酸の含有量が０．００５％未満であると、本発明の効果が発揮できないことがあり、一方、１％超過であると、溶解性が十分でなく、好ましくない。 The content of fumaric acid used is 0.005 to 1% by mass (hereinafter, "mass%" is simply referred to as "%"), more preferably 0.03 to 1% by mass, based on the total amount of the virus-inactivated preparation. It is desirable to set it to 0.6%.
If the content of fumaric acid is less than 0.005%, the effect of the present invention may not be exhibited, while if it exceeds 1%, the solubility is not sufficient, which is not preferable.
　また、本第２発明では、上記フマル酸単独でインフルエンザウイルス、ノロウイルス（ネコカリシウイルス代替）に対して不活化成分として作用するものであるが、更に、製品安定性の点、貯蔵安定性の点から、フマル酸とエタノールとを併用することができる。
　この併用の場合における、フマル酸の含有量は、ウイルス不活化製剤全量に対して、上記フマル酸単独の場合と同様（０．００５～１％、好ましくは、０．０１～０．６％）であり、エタノールの含有量は、好ましくは、５０％以下、更に好ましくは、５～４０％、特に好ましくは、１０～４０％であることが望ましい。
　このエタノールの含有量を５０％以下とすることにより、危険物でなく、安全に取り扱い、また、安全に保管することができ、しかも、手にやさしく対応できものとなる。更に、５％以上とすることにより、製品・貯蔵安定性に優れた製品とすることができる。 Further, in the second invention, the fumaric acid alone acts as an inactivating component against influenza virus and norovirus (substitute for feline calicivirus), but further, in terms of product stability and storage stability. Therefore, fumaric acid and ethanol can be used in combination.
In the case of this combined use, the content of fumaric acid is the same as in the case of the above-mentioned fumaric acid alone (0.005 to 1%, preferably 0.01 to 0.6%) with respect to the total amount of the virus-inactivated preparation. The ethanol content is preferably 50% or less, more preferably 5 to 40%, and particularly preferably 10 to 40%.
By setting the content of this ethanol to 50% or less, it is not a dangerous substance, can be handled safely, can be stored safely, and can be handled easily by hand. Further, by setting it to 5% or more, it is possible to obtain a product having excellent storage stability.
　上記第１発明及び第２発明のウイルス不活化製剤は、好ましくは、抗ウイルス効果の点から、そのｐＨを２．０～５．５、更に好ましくは、２．２～４．０とすることが望ましい。
　このｐＨを２．０以上とすることにより、手肌に優しい抗ウイルス剤とすることができ、一方、ｐＨを５．５以下とすることにより、強い抗ウイルス効果製剤とすることができる。
　上記ｐＨ範囲（２．０～５．５）の調整は、上記フマル酸の含有量の調整により、また、エタノールを併用する場合は、エタノールの含有量の調整により、更に、残部となる水（水道水、蒸留水、イオン交換水、精製水、純水、超純水など）の含有量により調整でき、更に、フマル酸塩・クエン酸塩・リンゴ酸塩・乳酸塩等の有機酸塩を添加することで、調整することができる。 The pH of the virus-inactivated preparations of the first invention and the second invention is preferably 2.0 to 5.5, more preferably 2.2 to 4.0, from the viewpoint of antiviral effect. Is desirable.
By setting the pH to 2.0 or higher, an antiviral agent that is gentle on the skin can be obtained, while by setting the pH to 5.5 or lower, a strong antiviral effect preparation can be obtained.
The pH range (2.0 to 5.5) is adjusted by adjusting the content of fumaric acid, and when ethanol is used in combination, the content of ethanol is adjusted to further adjust the remaining water (remaining water (). It can be adjusted by the content of tap water, distilled water, ion-exchanged water, purified water, pure water, ultra-pure water, etc. It can be adjusted by adding it.
　また、上記第１発明及び第２発明のウイルス不活化製剤は、好ましくは、可溶化性の点、製品安定性の点、防カビ効果の点から、グリセリン脂肪酸エステル、ポリグリセリン脂肪酸エステル、キサンタンガム、安息香酸ナトリウム、ソルビン酸カリウム、ポリリジン、デヒドロ酢酸及びデヒドロ酢酸ナトリウムから選ばれる少なくとも１種を含有することが好ましい。
　これらの成分は食品添加物として使用されているものであり、その安全性は確認されている。 Further, the virus inactivating preparations of the first invention and the second invention are preferably glycerin fatty acid ester, polyglycerin fatty acid ester, xanthan gum, from the viewpoint of solubilization, product stability, and antifungal effect. It preferably contains at least one selected from sodium benzoate, potassium sorbate, polylysine, dehydroacetic acid and sodium dehydroacetate.
These ingredients are used as food additives, and their safety has been confirmed.
　上記グリセリン脂肪酸エステル、ポリグリセリン脂肪酸エステル、キサンタンガムは、フマル酸の難溶性（水への溶解度：２５℃、０．６３ｇ／１００ｍＬ）を勘案し、ウイルス不活化製剤中での分散性能、分散安定性を向上させると共に、保湿成分として有用であり、好ましくは、ウイルス不活化製剤全量に対して、合計含有量を好ましくは、０．００１～２０％、更に好ましくは、０．００３～１７．５％とすることが望ましい。 The above-mentioned glycerin fatty acid ester, polyglycerin fatty acid ester, and xanthan gum take into consideration the poor solubility of fumaric acid (solubility in water: 25 ° C., 0.63 g / 100 mL), and disperse performance and dispersion stability in virus-inactivated preparations. The total content is preferably 0.001 to 20%, more preferably 0.003 to 17.5%, based on the total amount of the virus-inactivating preparation. Is desirable.
　より好ましくは、第１発明では、フマル酸は、予め所定の体積平均粒子径となるフマル酸がグリセリン脂肪酸エステル、ポリグリセリン脂肪酸エステル、キサンタンガムの上記分散安定剤等で分散された水分散液を用いることが好ましく、特に好ましくは、組成物全量に対して、体積平均粒子径が１０μｍ以下の上記所定量のフマル酸と、キサンタンガム０．０１～５％、グリセリン脂肪酸エステル０．０２５～１２．５％、残部となる上記水を含有するフマル酸水分散液を用いることが望ましい。
　また、第２発明では、組成物全量に対して、体積平均粒子径が１０μｍ以下の上記所定量のフマル酸と、上記所定量のエタノールと、キサンタンガム０．０１～５％、グリセリン脂肪酸エステル０．０２５～１２．５％、残部となる上記水を含有するフマル酸エタノール水分散液を用いることが望ましい。 More preferably, in the first invention, as the fumaric acid, an aqueous dispersion in which fumaric acid having a predetermined volume average particle size is dispersed in advance with the glycerin fatty acid ester, polyglycerin fatty acid ester, the dispersion stabilizer of xanthan gum or the like is used. It is preferable, and particularly preferably, the above-mentioned predetermined amount of fumaric acid having a volume average particle size of 10 μm or less, xanthan gum 0.01 to 5%, and glycerin fatty acid ester 0.025 to 12.5% with respect to the total amount of the composition. It is desirable to use an aqueous dispersion of fumaric acid containing the above-mentioned water as a balance.
Further, in the second invention, the above-mentioned predetermined amount of fumaric acid having a volume average particle diameter of 10 μm or less, the above-mentioned predetermined amount of ethanol, xanthan gum 0.01 to 5%, and glycerin fatty acid ester 0. It is desirable to use an aqueous dispersion of ethanol fumarate containing 025 to 12.5% and the balance of the above water.
　また、上記安息香酸ナトリウム、ソルビン酸カリウム、ポリリジン、デヒドロ酢酸及びデヒドロ酢酸ナトリウムは、食品・化粧品で用いられている保存料であり、必要に応じて、これらの成分を含有させることで、フマル酸単独の場合などの防カビ対策、保存安定性を更に実現することができ、好ましくは、ウイルス不活化製剤全量に対して、合計含有量で０．０１～５％、更に好ましくは、０．１～２％とすることが望ましい。 In addition, the above-mentioned sodium benzoate, potassium sorbate, polylysine, dehydroacetic acid and sodium dehydroacetate are preservatives used in foods and cosmetics, and fumaric acid can be added by containing these components as necessary. It is possible to further realize antifungal measures and storage stability when used alone, and the total content is preferably 0.01 to 5%, more preferably 0.1, based on the total amount of the virus-inactivated preparation. It is desirable to set it to ~ 2%.
　このように構成される本発明の第１発明、第２発明の各ウイルス不活化製剤は、取り扱い性に優れ、安全かつ効率よくインフルエンザウイルス、ノロウイルス、新型コロナウイルス（SARS-CoV2）の不活化を実現できる。特に、ノロウイルス（ネコカリシウイルスによる代替実験による）、インフルエンザウイルス、新型コロナウイルス（SARS-CoV2）の不活化効果が顕著である。
　本発明のウイルス不活化剤は、食品工場、喫茶店、レストラン、ホテル、居酒屋、学校給食、セントラルキッチン、スーパーのバックヤード等の調理台、病院・介護施設、及びこれら施設の空間、冷蔵庫、保管庫のほか、テーブル、机、出入口のドアノブ等の硬表面、エレベーターの押しボタン、ＰＣなどの画面、スマートフォン等のタッチ面などウイルスの付着する恐れがある部分に適用することができる。
　マスク・タオル・シーツ・布巾・テーブルクロス・ウェットシート・除菌ウェットシート・白衣・衣料等、皮膚と接触する製品にも適用できる。
　また、本発明のウイルス不活化剤は、マスク・タオル・シーツ・布巾・テーブルクロス・カーテン・白衣・衣料等の繊維、又は、床板・畳・壁・襖・椅子・テーブル・ドア・キッチン設備・調理台等の屋内設備、および、自動車の内装材等に、ウイルス不活化剤（フマル酸水溶液）に浸漬、もしくは散布後、乾燥する方法にて、フマル酸を固定し、抗ウイルス加工を施すことができる。更に、抗ウイルス効果を長期持続するために、ウイルス不活化剤にアクリル系・ポリウレタン系・ポリエステル系等の所定濃度のバインダーを併用（配合）して使用することができる。 The virus inactivating preparations of the first invention and the second invention of the present invention configured in this way are excellent in handleability, and safely and efficiently inactivate influenza virus, norovirus, and new coronavirus (SARS-CoV2). realizable. In particular, the inactivating effects of norovirus (based on alternative experiments with feline calicivirus), influenza virus, and new coronavirus (SARS-CoV2) are remarkable.
The virus inactivating agent of the present invention includes food factories, coffee shops, restaurants, hotels, taverns, school meals, central kitchens, kitchen tables such as supermarket backyards, hospitals / nursing facilities, and spaces, refrigerators, and storages of these facilities. In addition, it can be applied to hard surfaces such as tables, desks, door knobs at doorways, push buttons of elevators, screens such as PCs, and touch surfaces such as smartphones where viruses may adhere.
It can also be applied to products that come into contact with the skin, such as masks, towels, sheets, cloths, tablecloths, wet sheets, disinfectant wet sheets, lab coats, and clothing.
Further, the virus inactivating agent of the present invention includes fibers such as masks, towels, sheets, cloths, tablecloths, curtains, white clothes, and clothing, or floorboards, tatami mats, walls, folds, chairs, tables, doors, kitchen equipment, etc. Immersing fumaric acid in indoor equipment such as kitchen tables and interior materials of automobiles by immersing it in a virus inactivating agent (aqueous fumaric acid solution) or spraying it, and then drying it to fix fumaric acid and apply anti-virus processing. Can be done. Further, in order to maintain the antiviral effect for a long period of time, a binder having a predetermined concentration such as acrylic, polyurethane or polyester can be used in combination (blended) with the virus inactivating agent.
　更に、フマル酸は、食品の酸味料として使用され、適用する濃度では、酸味もほとんどなく無臭・無色透明であり、農水産物等の生鮮品や、口腔・鼻腔・皮膚へも適用できる。
　ウイルス不活化剤の使用方法としては特に限定されないが、例えば、対象物をウイルス不活化剤に浸漬、対象物にウイルス不活化剤を塗布又は噴霧（例えば、トリガースプレー、ディスペンサースプレー、エアゾール等）し、そのまま自然乾燥してもよいし、風乾、拭き取り等をして使用することができる。対象物に塗布又は噴霧する量としては、対象物にまんべんなく塗布又は噴霧できればよく、その量は特に限定されないが、例えば、約１～２０ｍＬである。
　また、本発明のウイルス不活化剤は不織布に含浸させてウイルス不活化材とすることもでき、これをウェットシートとしてふき取り作業を行うことにより、効率的にウイルス不活化することができる。 Furthermore, fumaric acid is used as an acidulant for foods, and at the applied concentration, it has almost no acidity and is odorless, colorless and transparent, and can be applied to fresh products such as agricultural and marine products, and to the oral cavity, nasal cavity, and skin.
The method of using the virus inactivating agent is not particularly limited, but for example, the object is immersed in the virus inactivating agent, and the virus inactivating agent is applied or sprayed on the object (for example, trigger spray, dispenser spray, aerosol, etc.). , It may be naturally dried as it is, or it can be used by air-drying, wiping, etc. The amount to be applied or sprayed on the object may be any amount as long as it can be applied or sprayed evenly on the object, and the amount is not particularly limited, but is, for example, about 1 to 20 mL.
Further, the virus inactivating agent of the present invention can be impregnated into a non-woven fabric to form a virus inactivating material, and the virus can be efficiently inactivated by wiping it as a wet sheet.
　次に、下記試験例により本発明を更に詳細に説明する。
〔試験例１：実施例１～２〕
　下記組成のサンプル１，２を用いて、下記試験法により、ウイルス不活化の試験（評価）を行った。なお、試験サンプル１，２のｐＨ値は、ｐＨメーター　ＨＭ－３０Ｇ（東亜ＤＫＫ社製）を用いて、液温２５℃で、測定した（後述する試験例２以降についても同様に測定した）。
　試験サンプル１の組成（全量１００％）：
　フマル酸（体積平均粒子径が１０μｍ、以下同様）　０．３％
　キサンタンガム　０．００２％
　グリセリン脂肪酸エステル　０．００５％
　水（精製水）　９９．６９３％
　ｐＨ値　２．３
　試験サンプル２の組成（全量１００％）：
　フマル酸　０．３％
　エタノール　５０％
　キサンタンガム　０．００２％
　グリセリン脂肪酸エステル　０．００５％
　水（精製水）　４９．６９３％
　ｐＨ値　２．３ Next, the present invention will be described in more detail with reference to the following test examples.
[Test Example 1: Examples 1 and 2]
Using the samples 1 and 2 having the following composition, a virus inactivation test (evaluation) was performed by the following test method. The pH values of the test samples 1 and 2 were measured using a pH meter HM-30G (manufactured by Toa DKK Corporation) at a liquid temperature of 25 ° C. (the same was also measured for Test Examples 2 and later described later).
Composition of test sample 1 (total amount 100%):
Fumaric acid (volume average particle size is 10 μm, the same applies below) 0.3%
Xanthan gum 0.002%
Glycerin fatty acid ester 0.005%
Water (purified water) 99.693%
pH value 2.3
Composition of test sample 2 (total amount 100%):
Fumaric acid 0.3%
50% ethanol
Xanthan gum 0.002%
Glycerin fatty acid ester 0.005%
Water (purified water) 49.693%
pH value 2.3
（試験方法）
　上記で調製した試験サンプル１，２を用いて、下記試験ウイルスにより、抗ウイルス試験、具体的には各試験サンプル溶液０．９ｍｌと試験ウイルス液０．１ｍｌを混和し、３０分間（５分間）静置する。その後、ＳＣＤＬＰ：９ｍｌを加え、１０倍希釈系列を作製し、プラーク法により作用後のウイルス感染価を求めた。この数値が小さい程、ウイルス感染価が小さいことを示す。
　これらの結果を下記表１に示す。
　試験ウイルス１：Ｆｅｌｉｎｅ　ｃａｌｉｃｉｖｉｒｕｓ　Ｆ－９株（ネコカリシウイルス、ＡＴＣＣ　ＶＲ－７８２）
　宿主細胞：ＣＲＦＫ細胞（ＡＴＣＣ　ＣＣＬ－９４）
　試験ウイルス２：Ｉｎｆｌｕｅｎｚａ　Ａ　ｖｉｒｕｓ　（Ｈ３Ｎ２）　Ａ／Ｈｏｎｇ　Ｋｏｎｇ／８／６８株（Ａ型インフルエンザウイルス、ＡＴＣＣ　ＶＲ－１６７９）
　宿主細胞：ＭＤＣＫ細胞（ＡＴＣＣ　ＣＣＬ－３４） (Test method)
Using the test samples 1 and 2 prepared above, antiviral test, specifically, 0.9 ml of each test sample solution and 0.1 ml of the test virus solution are mixed with the following test virus for 30 minutes (5 minutes). Let it stand still. Then, 9 ml of SCDLP was added to prepare a 10-fold diluted series, and the viral infectious titer after the action was determined by the plaque method. The smaller this number, the smaller the viral load.
These results are shown in Table 1 below.
Test virus 1: Feline calicivirus F-9 strain (feline calicivirus, ATCC VR-782)
Host cell: CRFK cell (ATCC CCL-94)
Test virus 2: Influenza A virus (H3N2) A / Hong Kong / 8/68 strain (influenza A virus, ATCC VR-1679)
Host cell: MDCK cell (ATCC CCL-34)
Figure JPOXMLDOC01-appb-T000001
  
Figure JPOXMLDOC01-appb-T000001
  
　上記表１の結果から明らかなように、サンプル１及びサンプル２は、感染価が定量以下の１０以下となり、抗ウイルス活性値は、５以上となった。
　本発明となる実施例１及び２（サンプル１、２）の抗ウイルス製剤は、非常に強い抗ウイルス効果を発揮することが判明した。 As is clear from the results in Table 1 above, the infectious titers of Sample 1 and Sample 2 were 10 or less, which was less than the quantitative amount, and the antiviral activity value was 5 or more.
It was found that the antiviral preparations of Examples 1 and 2 (Samples 1 and 2) according to the present invention exert a very strong antiviral effect.
〔試験例２～６〕
　次に、下記試験例２～６で、フマル酸と他の有機酸（クエン酸、乳酸）との比較によるウイルス不活化試験、フマル酸の濃度変化によるウイルス不活化試験、フマル酸とエタノールとの併用によるウイルス不活化試験、フマル酸の作用時間の変化によるウイルス不活化試験、新型コロナウイルス（SARS-CoV2）に対するウイルス不活化試験（上記抗ウイルス活性値を算出）を行った。なお、各サンプル溶液において、フマル酸などの濃度が同じサンプルの場合、ｐＨ値の記載は以後省略する。 [Test Examples 2 to 6]
Next, in Test Examples 2 to 6 below, a virus inactivation test by comparing fumaric acid with other organic acids (citrate, lactic acid), a virus inactivation test by changing the concentration of fumaric acid, and fumaric acid and ethanol. A virus inactivation test by combined use, a virus inactivation test by changing the action time of fumaric acid, and a virus inactivation test against the new corona virus (SARS-CoV2) (the above antiviral activity value was calculated) were performed. If the concentration of fumaric acid or the like is the same in each sample solution, the description of the pH value will be omitted hereafter.
〔試験例２：実施例３及び比較例１～２〕
　下記表２に示す試験区を用いて、下記試験ウイルスにより、抗ウイルス試験、具体的には各試験サンプル溶液０．９ｍｌと試験ウイルス液０．１ｍｌを混和し、３０分間静置する。その後、ＳＣＤＬＰ：９ｍｌを加え、１０倍希釈系列を作製し、プラーク法により作用後のウイルス感染価を求め、抗ウイルス活性値を求めた。
　これらの結果を下記表２に示す。
　試験ウイルス：Ｆｅｌｉｎｅ　ｃａｌｉｃｉｖｉｒｕｓ　Ｆ－９株
（ネコカリシウイルス、ＡＴＣＣ　ＶＲ－７８２）
　宿主細胞：ＣＲＦＫ細胞（ＡＴＣＣ　ＣＣＬ－９４） [Test Example 2: Example 3 and Comparative Examples 1 and 2]
Using the test group shown in Table 2 below, an antiviral test, specifically, 0.9 ml of each test sample solution and 0.1 ml of the test virus solution are mixed with the following test virus and allowed to stand for 30 minutes. Then, 9 ml of SCDLP was added to prepare a 10-fold diluted series, and the virus infectivity value after the action was determined by the plaque method, and the antiviral activity value was determined.
These results are shown in Table 2 below.
Test virus: Feline calicivirus F-9 strain (feline calicivirus, ATCC VR-782)
Host cell: CRFK cell (ATCC CCL-94)
Figure JPOXMLDOC01-appb-T000002
  
Figure JPOXMLDOC01-appb-T000002
  
〔試験例３：実施例４～６及び比較例３〕
　下記表３に示す試験区を用いて、下記試験ウイルスにより、抗ウイルス試験、具体的には各試験サンプル溶液０．９ｍｌと試験ウイルス液０．１ｍｌを混和し、３０分間静置する。その後、ＳＣＤＬＰ：９ｍｌを加え、１０倍希釈系列を作製し、プラーク法により作用後のウイルス感染価を求め、抗ウイルス活性値を求めた。
　これらの結果を下記表３に示す。
　試験ウイルス：Ｉｎｆｌｕｅｎｚａ　Ａ　ｖｉｒｕｓ　（Ｈ３Ｎ２）
　Ａ／Ｈｏｎｇ　Ｋｏｎｇ／８／６８株
　（Ａ型インフルエンザウイルス、ＡＴＣＣ　ＶＲ－１６７９）
　宿主細胞　　：ＭＤＣＫ細胞（ＡＴＣＣ　ＣＣＬ－３４） [Test Example 3: Examples 4 to 6 and Comparative Example 3]
Using the test group shown in Table 3 below, an antiviral test, specifically, 0.9 ml of each test sample solution and 0.1 ml of the test virus solution are mixed with the following test virus and allowed to stand for 30 minutes. Then, 9 ml of SCDLP was added to prepare a 10-fold diluted series, and the virus infectivity value after the action was determined by the plaque method, and the antiviral activity value was determined.
These results are shown in Table 3 below.
Test virus: Influenza A virus (H3N2)
A / Hong Kong / 8/68 strain (Influenza A virus, ATCC VR-1679)
Host cell: MDCK cell (ATCC CCL-34)
Figure JPOXMLDOC01-appb-T000003
  
Figure JPOXMLDOC01-appb-T000003
  
〔試験例４：実施例７～９〕
　下記表４に示す試験区を用いて、下記試験ウイルスにより、抗ウイルス試験、具体的には各試験サンプル溶液０．９ｍｌと試験ウイルス液０．１ｍｌを混和し、５分間静置する。その後、ＳＣＤＬＰ：９ｍｌを加え、１０倍希釈系列を作製し、プラーク法により作用後のウイルス感染価を求め、抗ウイルス活性値を求めた。
　これらの結果を下記表４に示す。
　試験ウイルス：Ｉｎｆｌｕｅｎｚａ　Ａ　ｖｉｒｕｓ　（Ｈ３Ｎ２）　Ａ／Ｈｏｎｇ　Ｋｏｎｇ／８／６８株（Ａ型インフルエンザウイルス、ＡＴＣＣ　ＶＲ－１６７９）
　宿主細胞　　：ＭＤＣＫ細胞（ＡＴＣＣ　ＣＣＬ－３４）
　試験ウイルス：Ｆｅｌｉｎｅ　ｃａｌｉｃｉｖｉｒｕｓ　Ｆ－９株（ネコカリシウイルス、ＡＴＣＣ　ＶＲ－７８２）
　宿主細胞　　：ＣＲＦＫ細胞（ＡＴＣＣ　ＣＣＬ－９４） [Test Example 4: Examples 7 to 9]
Using the test group shown in Table 4 below, an antiviral test, specifically, 0.9 ml of each test sample solution and 0.1 ml of the test virus solution are mixed with the following test virus and allowed to stand for 5 minutes. Then, 9 ml of SCDLP was added to prepare a 10-fold diluted series, and the virus infectivity value after the action was determined by the plaque method, and the antiviral activity value was determined.
These results are shown in Table 4 below.
Test virus: Influenza A virus (H3N2) A / Hong Kong / 8/68 strain (influenza A virus, ATCC VR-1679)
Host cell: MDCK cell (ATCC CCL-34)
Test virus: Feline calicivirus F-9 strain (feline calicivirus, ATCC VR-782)
Host cell: CRFK cell (ATCC CCL-94)
Figure JPOXMLDOC01-appb-T000004
Figure JPOXMLDOC01-appb-T000004
〔試験例５：実施例１０～１７〕
　下記表５、表６に示す試験ウイルスにより、抗ウイルス試験、具体的には各試験サンプル溶液０．９ｍｌと試験ウイルス液０．１ｍｌを混和し、一定時間（１５秒、３０秒、６０秒、３０分）静置する。その後、ＳＣＤＬＰ：９ｍｌを加え、１０倍希釈系列を作製し、プラーク法により作用後のウイルス感染価を求め、抗ウイルス活性値を求めた。
　これらの結果を下記表５、表６に示す。 [Test Example 5: Examples 10 to 17]
The anti-virus test, specifically 0.9 ml of each test sample solution and 0.1 ml of the test virus solution, were mixed with the test viruses shown in Tables 5 and 6 below for a certain period of time (15 seconds, 30 seconds, 60 seconds, 30 minutes) Let stand. Then, 9 ml of SCDLP was added to prepare a 10-fold diluted series, and the virus infectivity value after the action was determined by the plaque method, and the antiviral activity value was determined.
These results are shown in Tables 5 and 6 below.
　試験ウイルス：Ｉｎｆｌｕｅｎｚａ　Ａ　ｖｉｒｕｓ　（Ｈ３Ｎ２）　Ａ／Ｈｏｎｇ　Ｋｏｎｇ／８／６８株（Ａ型インフルエンザウイルス、ＡＴＣＣ　ＶＲ－１６７９）
　宿主細胞　　：ＭＤＣＫ細胞（ＡＴＣＣ　ＣＣＬ－３４）
　試験ウイルス：Ｆｅｌｉｎｅ　ｃａｌｉｃｉｖｉｒｕｓ　
　Ｆ－９株（ネコカリシウイルス、ＡＴＣＣ　ＶＲ－７８２）
　宿主細胞　　：ＣＲＦＫ細胞（ＡＴＣＣ　ＣＣＬ－９４） Test virus: Influenza A virus (H3N2) A / Hong Kong / 8/68 strain (influenza A virus, ATCC VR-1679)
Host cell: MDCK cell (ATCC CCL-34)
Test virus: Feline calicivirus
F-9 strain (feline calicivirus, ATCC VR-782)
Host cell: CRFK cell (ATCC CCL-94)
Figure JPOXMLDOC01-appb-T000005
Figure JPOXMLDOC01-appb-T000005
Figure JPOXMLDOC01-appb-T000006
Figure JPOXMLDOC01-appb-T000006
〔試験例６：実施例１８～１９〕
　下記試験方法により、新型コロナウイルス（SARS-CoV-2）への効果について試験した。
（試験方法）
１）下記表７に示す組成の液90μlに、ウイルス液10μlを加える。
２）室温で、１分間静置する。
３）10μlをとり、1000μlの細胞培養液へ懸濁する（1/100希釈）。
４）96-wellプレートを用いて、段階希釈する（TCID50法）
５）３日後に、TCID50値を測定し、ウイルス量を算出する。
　※新型コロナウイルス (国立感染症より分与)
　　ウイルス名　：SARS-CoV-2
　　ウイルス株名：JPN/TY/WK-521
　　GISAID　　　: EPI_ISL_408667
　　Reference　 :  Matsuyama S et al., PNAS 2020, 117: 7001-7003
　※培養細胞
　　細胞株：VeroE6/TMPRSS2
　　培養液：DMEM low Glc 10% FCS
　これらの結果を下記表７に示す。 [Test Example 6: Examples 18 to 19]
The effect on the new coronavirus (SARS-CoV-2) was tested by the following test method.
(Test method)
1) Add 10 μl of the virus solution to 90 μl of the solution having the composition shown in Table 7 below.
2) Let stand for 1 minute at room temperature.
3) Take 10 μl and suspend in 1000 μl cell culture medium (1/100 dilution).
4) Using a 96-well plate, serially dilute (TCID50 method)
5) After 3 days, the TCID50 value is measured and the viral load is calculated.
* New coronavirus (distributed from national infectious diseases)
Virus name: SARS-CoV-2
Virus strain name: JPN / TY / WK-521
GISAID: EPI_ISL_408667
Reference: Matsuyama S et al., PNAS 2020, 117: 7001-7003
* Cultured cell line: VeroE6 / TMPRSS2
Culture medium: DMEM low Glc 10% FCS
These results are shown in Table 7 below.
Figure JPOXMLDOC01-appb-T000007
   
Figure JPOXMLDOC01-appb-T000007
   
〔試験例７：実施例２０〕
　下記試験方法によりフマル酸加工生地のインフルエンザウイルスへの効果について試験した。
　ポリエステル生地（株式会社色染社製）を、０．３%のフマル酸液に浸漬し、絞った後に（絞り率１１０～１１５％）、８０℃にて送風乾燥し、下記表８に示す付着量のフマル酸加工ＰＥＴ生地を作成した。このフマル酸加工生地を用いて、インフルエンザウイルスの抗ウイルス試験を実施した。試験方法〔ＪＩＳ Ｌ １９２２（ISO 18184）に準拠）〕を下記に示す。 [Test Example 7: Example 20]
The effect of fumaric acid-processed dough on influenza virus was tested by the following test method.
The polyester fabric (manufactured by Color Dyeing Co., Ltd.) is immersed in a 0.3% fumaric acid solution, squeezed (squeezing ratio 110 to 115%), blown and dried at 80 ° C., and adhered as shown in Table 8 below. An amount of fumaric acid processed PET dough was prepared. An antiviral test for influenza virus was carried out using this fumaric acid-processed dough. The test method [Compliant with JIS L 1922 (ISO 18184)] is shown below.
（試験方法）
１．各試験品に、試験ウイルス液を接種する（標準２００μｌ／試験品）
２．２５℃で２時間静置する。
　（「接種直後」の対照試料は、静置せずにすぐに回収する）
３．ＳＣＤＬＰ培地２０ｍｌを加え、中和及びウイルスの回収を行う。
４．１０倍の段階希釈系列を作成する。
５．用意しておいた宿主細胞に、それぞれ回収原液及び希釈液を接種する。
６．１時間後、寒天培地を重層する。
７．４日間培養後、固定し、寒天を除去した後染色を行う。
８．プラークの数を目視で測定し、ウイルスの感染価を求める。
９．得られた感染価より、抗ウイルス活性値を算出する。
　この試験結果を下記表８に示す。
　試験ウイルス：Ｉｎｆｌｕｅｎｚａ　Ａ　ｖｉｒｕｓ　（Ｈ３Ｎ２）　Ａ／Ｈｏｎｇ　Ｋｏｎｇ／８／６８株（Ａ型インフルエンザウイルス、ＡＴＣＣ　ＶＲ－１６７９） (Test method)
1. 1. Inoculate each test product with the test virus solution (standard 200 μl / test product)
Let stand at 2.25 ° C for 2 hours.
(Control samples "immediately after inoculation" should be collected immediately without standing.)
3. 3. Add 20 ml of SCDLP medium to neutralize and recover the virus.
4. Create a 10-fold serial dilution series.
5. The prepared host cells are inoculated with the recovered stock solution and the diluted solution, respectively.
After 6.1 hours, the agar medium is layered.
After culturing for 7.4 days, the cells are fixed, agar is removed, and then staining is performed.
8. Visually measure the number of plaques to determine the infectious titer of the virus.
9. The antiviral activity value is calculated from the obtained infection titer.
The test results are shown in Table 8 below.
Test virus: Influenza A virus (H3N2) A / Hong Kong / 8/68 strain (influenza A virus, ATCC VR-1679)
Figure JPOXMLDOC01-appb-T000008
Figure JPOXMLDOC01-appb-T000008
〔試験例８：実施例２１〕
　フマル酸加工生地のネコカリシウイルスへの効果について試験した。
　ポリエステル生地（株式会社色染社）を、０．６％のフマル酸液に浸漬し、絞った後に（絞り率１１０～１１５％）、８０℃にて送風乾燥し、下記表６に示すフマル酸加工ＰＥＴ生地を作成した。フマル酸加工生地を用い、抗ウイルス試験を実施し、抗ウイルス活性値を求めた。
　試験ウイルスとして、ネコカリシウイルスを用い、操作は、上記試験例７と同様の方法で抗ウイルス試験を実施した。
　これらの結果を下記表９示す。
　試験ウイルス：Ｆｅｌｉｎｅ　ｃａｌｉｃｉｖｉｒｕｓ　Ｆ－９株（ネコカリシウイルス、ＡＴＣＣ　ＶＲ－７８２） [Test Example 8: Example 21]
The effect of fumaric acid-processed dough on feline calicivirus was tested.
The polyester fabric (color dyeing company Co., Ltd.) is immersed in a 0.6% fumaric acid solution, squeezed (squeezing ratio 110 to 115%), blown and dried at 80 ° C., and the fumaric acid shown in Table 6 below is used. A processed PET fabric was created. An antiviral test was carried out using a fumaric acid-processed dough, and an antiviral activity value was determined.
Feline calicivirus was used as the test virus, and the antiviral test was carried out in the same manner as in Test Example 7 above.
These results are shown in Table 9 below.
Test virus: Feline calicivirus F-9 strain (feline calicivirus, ATCC VR-782)
Figure JPOXMLDOC01-appb-T000009
  
 
Figure JPOXMLDOC01-appb-T000009
  
 
〔試験例９：実施例２２～２６〕
　フマル酸加工生地の抗ウイルス効果（バインダー併用）について試験した。
　上記表７に示すフマル酸＋バインダー加工ポリエステル生地（株式会社色染社）を作成し、抗ウイルス効果について評価した。
　試験ウイルスとして、ネコカリシウイルスを用い、操作は、上記試験例７と同様の方法で抗ウイルス試験を実施した。
　これらの結果を下記表１０に示す。
　試験ウイルス：Ｉｎｆｌｕｅｎｚａ　Ａ　ｖｉｒｕｓ　（Ｈ３Ｎ２）　Ａ／Ｈｏｎｇ　Ｋｏｎｇ／８／６８株（Ａ型インフルエンザウイルス、ＡＴＣＣ　ＶＲ－１６７９） [Test Example 9: Examples 22 to 26]
The antiviral effect (combined with a binder) of the fumaric acid-processed dough was tested.
The fumaric acid + binder-processed polyester fabric (color dyeing company Co., Ltd.) shown in Table 7 above was prepared and evaluated for its antiviral effect.
Feline calicivirus was used as the test virus, and the antiviral test was carried out in the same manner as in Test Example 7 above.
These results are shown in Table 10 below.
Test virus: Influenza A virus (H3N2) A / Hong Kong / 8/68 strain (influenza A virus, ATCC VR-1679)
Figure JPOXMLDOC01-appb-T000010
  
※抗ウイルス活性値：２以上（高価あり）、３以上（十分な効果あり）
　上記表１０中の各バインダー名は、下記のとおりである。
　モビニール963　　　　：日本合成化学工業株式会社（アクリル系）
　ライトエポックTF3500 ：北広ケミカル株式会社（シリコン系）
　エバファノールN-33　 ：日華化学株式会社（ウレタン系）
　ポリエスターWR901　　 ：三菱ケミカル株式会社（ポリエステル系）
　ニカゾール-RX-7013ED　：日本カーバイド株式会社（アクリル系）
Figure JPOXMLDOC01-appb-T000010
* Antiviral activity value: 2 or more (expensive), 3 or more (sufficient effect)
The names of the binders in Table 10 above are as follows.
Mobile 963: Nippon Synthetic Chemical Industry Co., Ltd. (acrylic)
Light Epoch TF3500: Hokko Chemicals Co., Ltd. (Silicon)
Evafanol N-33: NICCA CHEMICAL CO., LTD. (Urethane type)
Polyester WR901: Mitsubishi Chemical Corporation (polyester type)
Nikazol-RX-7013ED: Nippon Carbide Co., Ltd. (acrylic)
　更に、上記試験例９に付随して、黄色ブドウ球菌（Staphylococcus
 aureus NBRC12732 ）を用いた試験を行った。
　試験方法は、「ＪＩＳ Ｌ １９０２：２００８(ISO 20743)、菌液吸収法」に準拠し、洗濯方法は、「ＪＩＳ Ｌ ０２１７、１０３号」に準拠して、下記２種の生地を用いて菌液吸収法による定量試験（抗菌活性値を算出）により行った。
　フマル酸－０．１％加工ＰＥＴ生地と、フマル酸－０．１％＋モビニール963-3％加工ＰＥＴ生地について試験した。この結果を下記表１１に示す。上記抗菌活性値Ａは、２．０≦Ａ≦３．０で「抗菌効果が認められる。」、３．０≦Ａで「強い効果が認められる。」との評価となっている。 Furthermore, in association with Test Example 9, Staphylococcus aureus (Staphylococcus)
A test was performed using aureus NBRC12732).
The test method is based on "JIS L 1902: 2008 (ISO 20743), bacterial solution absorption method", and the washing method is based on "JIS L 0217, 103", using the following two types of dough. It was carried out by a quantitative test (calculation of antibacterial activity value) by the liquid absorption method.
Fumaric acid-0.1% processed PET dough and fumaric acid-0.1% + mobile 963-3% processed PET dough were tested. The results are shown in Table 11 below. The antibacterial activity value A is evaluated as "an antibacterial effect is recognized" when 2.0≤A≤3.0 and "a strong effect is observed" when 3.0≤A.
Figure JPOXMLDOC01-appb-T000011
  
Figure JPOXMLDOC01-appb-T000011
  
　上記表１～１１の結果（実施例１～２６、参考例１，２及び比較例１～３）を綜合的に考察すると、本発明となるウイルス不活化剤は、ノロウイルス、インフルエンザウイルス、新型コロナウイルス（SARS-CoV2）への不活化効果が認められ、その作業時間も１５秒の短時間でも高い抗ウイルス効果を有することが確認された。
　上記試験例７～９の結果を含めて考察すると、フマル酸のみも、バインダー併用も、抗ウイルス活性値は、４．４となり、高い抗ウイルス効果を有することが確認された。上記バインダーを併用するメリットとしては、フマル酸濃度を下げても同等の効果を示すことができ、また、洗濯耐性などが要求される場合にも、好ましい態様となることが判った。 Considering the results of Tables 1 to 11 above (Examples 1 to 26, Reference Examples 1 and 2 and Comparative Examples 1 to 3), the virus inactivating agent according to the present invention is norovirus, influenza virus, and new corona. It was confirmed that it had an inactivating effect on the virus (SARS-CoV2), and that it had a high anti-virus effect even in a short working time of 15 seconds.
Considering the results of Test Examples 7 to 9 above, it was confirmed that both fumaric acid alone and the combined use of the binder had an antiviral activity value of 4.4 and had a high antiviral effect. It was found that the merit of using the above binder in combination is that the same effect can be exhibited even if the concentration of fumaric acid is lowered, and that it is a preferable embodiment even when washing resistance or the like is required.
　取り扱い性に優れ、無臭であり、安全かつ効率よくインフルエンザウイルス、ノロウイルス、新型コロナウイルス（SARS-CoV2）の不活化を実現できるウイルス不活化製剤が得られる。 A virus inactivating preparation that is easy to handle, odorless, and can safely and efficiently inactivate influenza virus, norovirus, and new coronavirus (SARS-CoV2) can be obtained.

Claims (7)

  1. 　フマル酸を主成分とすることを特徴とするウイルス不活化剤。 A virus inactivating agent characterized by containing fumaric acid as the main component.
  2. 　フマル酸とエタノールとを含有することを特徴とするウイルス不活化剤。 A virus inactivating agent characterized by containing fumaric acid and ethanol.
  3. 　エタノールの含有量が５０質量％以下であることを特徴とする請求項２に記載のウイルス不活化剤。 The virus inactivating agent according to claim 2, wherein the content of ethanol is 50% by mass or less.
  4. 　フマル酸の含有量が０．００５～１質量％であることを特徴とする請求項１～３のいずれか一つに記載のウイルス不活化剤。 The virus inactivating agent according to any one of claims 1 to 3, wherein the content of fumaric acid is 0.005 to 1% by mass.
  5. 　ウイルス不活化剤のｐＨが２．０～５．５であることを特徴とする請求項１～４のいずれか一つに記載のウイルス不活化剤。 The virus inactivating agent according to any one of claims 1 to 4, wherein the pH of the virus inactivating agent is 2.0 to 5.5.
  6. 　グリセリン脂肪酸エステル、ポリグリセリン脂肪酸エステル、キサンタンガム、安息香酸ナトリウム、ソルビン酸カリウム、ポリリジン、デヒドロ酢酸及びデヒドロ酢酸ナトリウムから選ばれる少なくとも１種を含有することを特徴とする請求項１～５のいずれか一つに記載のウイルス不活化剤。 Any one of claims 1 to 5, which comprises at least one selected from glycerin fatty acid ester, polyglycerin fatty acid ester, xanthan gum, sodium benzoate, potassium sorbate, polylysine, dehydroacetic acid and sodium dehydroacetate. The virus inactivating agent described in one.
  7. 　不活化できるウイルスがインフルエンザウイルス、ネコカリシウイルス、新型コロナウイルス（SARS-CoV2）であることを特徴とする請求項１～６のいずれか一つに記載のウイルス不活化剤。 The virus inactivating agent according to any one of claims 1 to 6, wherein the virus that can be inactivated is influenza virus, feline calicivirus, and new coronavirus (SARS-CoV2).
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