WO2022102590A1 - Anti-viral agent - Google Patents

Anti-viral agent Download PDF

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Publication number
WO2022102590A1
WO2022102590A1 PCT/JP2021/041065 JP2021041065W WO2022102590A1 WO 2022102590 A1 WO2022102590 A1 WO 2022102590A1 JP 2021041065 W JP2021041065 W JP 2021041065W WO 2022102590 A1 WO2022102590 A1 WO 2022102590A1
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WIPO (PCT)
Prior art keywords
virus
tea
antiviral agent
antiviral
agent according
Prior art date
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PCT/JP2021/041065
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French (fr)
Japanese (ja)
Inventor
修 松田
えり子 扇谷
政春 新屋
正己 一谷
誠 小林
孝宣 瀧原
仁 衣笠
Original Assignee
株式会社 伊藤園
京都府公立大学法人
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Application filed by 株式会社 伊藤園, 京都府公立大学法人 filed Critical 株式会社 伊藤園
Priority to JP2022561920A priority Critical patent/JPWO2022102590A1/ja
Publication of WO2022102590A1 publication Critical patent/WO2022102590A1/en

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    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L2/00—Non-alcoholic beverages; Dry compositions or concentrates therefor; Their preparation
    • A23L2/52—Adding ingredients
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/105—Plant extracts, their artificial duplicates or their derivatives
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline 
    • A61K31/353—3,4-Dihydrobenzopyrans, e.g. chroman, catechin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/82—Theaceae (Tea family), e.g. camellia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
    • 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
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A61Q19/10—Washing or bathing preparations
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
    • C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
    • C07D311/58—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4
    • C07D311/60—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4 with aryl radicals attached in position 2
    • C07D311/62—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4 with aryl radicals attached in position 2 with oxygen atoms directly attached in position 3, e.g. anthocyanidins

Definitions

  • the present invention relates to an antiviral agent or the like.
  • Coronavirus is a species of virus belonging to the coronavirus subfamily of the coronavirus family, and is a plus-strand RNA virus that infects humans and animals and causes respiratory, digestive, vascular, or neurological diseases. Coronavirus can be transmitted from any infected host animal and cause a large-scale infectious disease in humans. Examples of coronaviruses include SARS coronavirus 1 (SARS-CoV-1), which was prevalent in 2002 and 2003, and Middle East respiratory syndrome coronavirus (MERS-CoV). Recently, a worldwide epidemic of SARS coronavirus 2 (SARS-CoV-2) has occurred, and since the treatment technology has not been established, serious damage continues in various fields such as medical care and economy.
  • SARS-CoV-1 SARS coronavirus 1
  • MERS-CoV Middle East respiratory syndrome coronavirus
  • An object of the present invention is to provide an antiviral agent, particularly an antiviral agent against a coronavirus such as SARS-CoV-2.
  • the present inventor has found that the above problems can be solved if it is an antiviral agent containing a tea component, particularly catechins or catechin oxidation polymers.
  • the present inventor has completed the present invention as a result of further research based on this finding. That is, the present invention includes the following aspects.
  • Item 1 An antiviral agent containing tea ingredients.
  • Item 2. The antiviral agent according to Item 1, wherein the tea component is polyphenols.
  • Item 3 The antiviral agent according to Item 2, wherein the polyphenols are catechins or catechin oxidation polymers.
  • Item 4. The antiviral agent according to Item 3, wherein the catechins are gallate-type catechins.
  • Item 5. The antiviral agent according to Item 3, wherein the catechin oxide polymers are theacinencins or theaflavins.
  • Item 6 The antivirus according to any one of Items 1 to 5 for use in at least one selected from the group consisting of suppression of virus infection, reduction of virus cell infection titer, suppression of cell death by virus, and virus inactivation. Agent.
  • Item 7 The antiviral agent according to any one of Items 1 to 6, wherein the virus is a coronavirus.
  • Item 8. The antiviral agent according to any one of Items 1 to 7, wherein the virus is SARS-CoV-2.
  • Item 9 The antiviral agent according to any one of Items 1 to 8, which is used for application to a living body.
  • Item 10 The antiviral agent according to Item 9, which is a pharmaceutical, cosmetics, beverage composition, food composition, food additive, disinfectant or detergent.
  • Item 11 The antiviral agent according to Item 9 or 10, which is a preventive or therapeutic agent for COVID-19.
  • Item 12. The antiviral agent according to any one of Items 1 to 8, which is used for applying to articles.
  • Item 13 The antiviral agent according to Item 12, which is a disinfectant or a cleaning agent.
  • Item 14 An antiviral method involving the application of tea ingredients to living organisms or articles.
  • Item 15 An antiviral method that involves ingesting tea ingredients in a subject with a viral infection.
  • Item 16 Tea ingredient for use as an antiviral agent.
  • Item 17 Use of tea ingredients for the production of antiviral agents.
  • Item 18 Use of tea ingredients as an antiviral agent.
  • an antiviral agent particularly an antiviral agent against a coronavirus such as SARS-CoV-2.
  • Test Example 1 The results of Test Example 1 are shown.
  • the vertical axis shows TCID 50/50 ⁇ L.
  • the horizontal axis shows the sample name and its concentration at the time of contact with the virus. In the horizontal axis, Control indicates the case where sterile water is used instead of the sample solution.
  • the Post protocol result of Test Example 2 is shown.
  • the vertical axis shows the OD value after crystal violet staining.
  • the horizontal axis shows the concentration of the sample solution at the time of use (before mixing with virus / cells).
  • the Mix protocol result of Test Example 2 is shown.
  • the vertical axis shows the OD value after crystal violet staining.
  • the horizontal axis shows the concentration of the sample solution at the time of use (before mixing with virus / cells).
  • the outline of the method of Test Example 3 is shown.
  • the results of the TCID 50 assay of Test Example 3 are shown.
  • the vertical axis shows TCID 50/50 ⁇ L.
  • the horizontal axis shows the sample name and its concentration at the time of contact with the virus.
  • Control indicates the case where sterile water is used instead of the sample solution.
  • the results of qRT-PCR of Test Example 3 are shown.
  • the vertical axis shows the relative value of the amount of viral RNA.
  • the horizontal axis shows the sample name and its concentration at the time of contact with the virus. In the horizontal axis, Control indicates the case where sterile water is used instead of the sample solution.
  • an antiviral agent containing a tea component and an antiviral agent containing a catechin oxidative polymer are collectively referred to as "the agent of the present invention” in the present specification. Sometimes.). This will be described below.
  • Active ingredient The active ingredient is a tea ingredient.
  • Tea ingredients include ingredients obtained from green tea, oolong tea, black tea, and post-fermented tea ("Tea Function: New Possibility of Biological Functions", Keiichiro Muramatsu et al. (Ed.), Academic Publishing Center, 2002).
  • the components obtained by extraction can be preferably used. It is not particularly limited as long as it is a component contained in tea or a component derived from the component, and includes either a single compound or a mixture of a plurality of compounds.
  • Tea is not particularly limited as long as it is obtained by extracting from a tea plant.
  • tea plant preferably include Camellia plants, and particularly preferably Camellia sinensis.
  • the part of the tea plant used for extraction is not particularly limited, and examples thereof include leaves and branches. Among these, leaves are preferably mentioned.
  • the tea plant used for extraction may be, for example, an unfermented one in which the enzyme is inactivated by heat treatment (for example, steaming, frying, roasting on fire, sun-drying, etc.) after harvesting, or the enzyme. It may be fermented (semi-fermented) to some extent by an enzyme by weakening the inactivation intensity of the enzyme or delaying the timing thereof, or it may not weaken the inactivation intensity of the enzyme or inactivate the enzyme. It may be completely fermented by an enzyme or the like, or it may be fermented by adding a microorganism such as lactic acid bacteria.
  • heat treatment for example, steaming, frying, roasting on fire, sun-drying, etc.
  • the tea plant used for extraction is preferably tea leaves.
  • the tea leaves include matcha tea leaves, roasted tea leaves, roasted tea leaves, new tea leaves, black tea leaves, pouer tea leaves, oolong tea leaves and the like.
  • examples of tea leaves include green tea leaves (for example, Tamaro, Bancha, brown rice tea, etc.), white tea leaves, yellow tea leaves, black tea leaves, flower tea leaves, and the like.
  • examples of the tea leaves include matcha tea leaves, roasted tea leaves, roasted tea leaves, new tea leaves, tea leaves, pouer tea leaves, oolong tea leaves, and the like, and more preferably matcha tea leaves, roasted tea leaves, and roasted tea leaves.
  • examples thereof include tea leaves of tea, tea leaves of tea, tea leaves of oolong tea, and particularly preferably tea leaves of matcha, tea leaves of roasted tea, and tea leaves of tea.
  • pretreatments such as steaming, rough kneading, kneading, medium kneading, fine kneading, drying, and squeezing can be performed.
  • the tea plant may be one kind alone or a combination of two or more kinds.
  • the extraction solvent is not particularly limited.
  • Extraction solvents include water; lower monohydric alcohols such as methanol, ethanol, propanol and butanol; liquid polyhydric alcohols such as glycerin, propylene glycol and 1,3-butylene glycol; ketones such as acetone; ethers such as ethyl ether.
  • Esters such as methyl acetate, ethyl acetate, propyl acetate, butyl acetate; supercritical carbon dioxide and the like.
  • the extraction solvent may be one kind alone or a combination of two or more kinds. Examples of the extraction solvent include a solvent containing water (for example, 50% by mass or more, 70% by mass or more, 80% by mass or more, 90% by mass or more, or 95% by mass or more), and water is particularly preferable. Be done.
  • the temperature of the solvent at the time of extraction is not particularly limited, but is, for example, 4 to 100 ° C, preferably 50 to 100 ° C, and more preferably 60 to 100 ° C.
  • the temperature can be appropriately set according to the type of tea plant and the like.
  • the amount of the extraction solvent used is not particularly limited, but is, for example, 1 to 2000 parts by mass, 5 to 1000 parts by mass, or 10 to 500 parts by mass with respect to 1 part by mass of the tea plant.
  • the amount used can be appropriately set according to the type of tea plant and the like.
  • the extraction time varies depending on the extraction method, solvent, temperature, etc., and is not particularly limited.
  • the extraction time is, for example, 10 seconds to 1 hour, or 30 seconds to 10 minutes.
  • the extraction time can be appropriately set according to the type of tea plant and the like.
  • the extraction residue can be removed as needed.
  • the method for removing is not particularly limited, and for example, a method such as free fall, centrifugation, or filtration can be adopted by one type or a combination of two or more types.
  • the properties of the tea component are not particularly limited and may be, for example, liquid, slurry, paste, solid, powder or the like.
  • the tea extract may be the extract itself, a concentrate of the extract (including a dried product), or a mixture thereof.
  • polyphenols particularly catechins and catechin oxidation polymers can be preferably used.
  • the catechins in the present invention are not particularly limited as long as they are derivatives in which flavan-3-ols are substituted with a plurality of hydroxy groups or aromatic carboxylic acid (for example, gallic acid) esters thereof. Specifically, it includes those described in "Functions of Tea: New Possibilities of Biological Functions" (Keiichiro Muramatsu et al. (Ed.), Society Publishing Center, 2002), pp. 35-41.
  • epigallocatechin gallate EGCG
  • epicatechin gallate ECC
  • galocacatechin gallate GCG
  • gallate-type catechins of catechin gallate CG
  • epigallocatechin ECC
  • epicatechin ECC
  • epicatechin ECC
  • EC Galocatechin
  • non-gallate-type catechins of catechin (C) can be mentioned as the active ingredient thereof.
  • the catechin oxidation polymer in the present invention is not particularly limited as long as it is a polymer produced from catechin through oxidation, but for example, theaflavins, oolontheanins, proanthocyanidins, assamicines, and oolonhomobisflavans. , Hydrolysable tannins, theaflavins, theaflavins, etc. (see the above book), preferably theacinencins, theaflavins, etc., among which theacinencin A and theaflavin digarates are most preferable. Can be used.
  • Teasinencins are dimers in which catechins are bound to each other in the B ring, and are typically the following general formula:
  • R 1 and R 2 are the same or different and indicate a hydrogen atom or a galloyl group. ] It is a compound represented by.
  • teasinencins for example, the general formula (Ia) or (Ib) :.
  • teasinencin A is particularly preferable.
  • theaflavins include theaflavins (non-gallate type theaflavins), theaflavins-3-monogallate, theaflavin-3'-monogallate, theaflavin-3,3'-digalate and other ester-type theaflavins (gallate-type theaflavins).
  • gallate-type theaflavins are preferable, and theaflavins-3,3'-digalate are more preferable.
  • any of the tea components may be a derivative, and examples thereof include a derivative of a catechin oxide polymer, a derivative of teacinencin, and a derivative of teasinencins.
  • the tea component may be obtained from tea (generated by oxidation treatment if necessary) or may be obtained from plants or foods other than tea. In those cases, it may be obtained by adding some process such as concentration and / or fractionation and / or purification. Further, the tea component may be synthesized and used.
  • the active ingredient may be one kind alone or a combination of two or more kinds.
  • the target virus of the agent of the present invention is not particularly limited.
  • viruses include influenza virus (for example, type A, type B, etc.), ruin virus, Ebola virus, corona virus, measles virus, varicella / herpes zoster virus, mumps virus, arbovirus, RS virus, SARS virus, hepatitis virus (for example).
  • influenza virus for example, type A, type B, etc.
  • ruin virus for example, type A, type B, etc.
  • Ebola virus corona virus
  • measles virus varicella / herpes zoster virus
  • mumps virus arbovirus
  • RS virus SARS virus
  • hepatitis virus for example.
  • hepatitis B virus, hepatitis C virus, etc. yellow fever virus
  • AIDS virus mad dog disease virus
  • hunter virus dengue virus
  • nipavirus lissavirus
  • other enveloped viruses enveloped viruses
  • coronavirus is particularly preferred.
  • Coronavirus is a virus belonging to the subfamily Orthocoronavirus.
  • the coronavirus include alpha coronavirus genus, beta coronavirus genus, gamma coronavirus genus, delta coronavirus genus, and the like, and among these, beta coronavirus genus is preferable.
  • the beta coronavirus genus include SARS-related coronavirus (SARSr-CoV), broad coronavirus HKU1, and MERS coronavirus, and among these, SARSr-CoV is preferable.
  • SARSr-CoV include SARS-CoV-2 and SARS-CoV-1, and among these, SARS-CoV-2 is preferable.
  • the agent of the present invention can be particularly preferably used for SARS-CoV-2.
  • the agent of the present invention can exert an antiviral action against a virus.
  • the antiviral action includes a virus infection suppressing action, a virus cell infecting titer lowering action, a virus-induced cell death suppressing action, a virus inactivating action, a virus growth suppressing action, a virus emergence suppressing action, and a virus.
  • the resistance-inducing action and the like can be mentioned.
  • the agent of the present invention is at least selected from the group consisting of virus infection suppression, virus cell infectivity-lowering agent, virus-induced cell death suppression, virus inactivation, virus growth suppression, virus germination suppression, and virus resistance induction. It can be used for one species. In addition, due to these actions, it can also be used as a prophylactic or therapeutic agent for coronavirus infections (particularly COVID-19).
  • the agent of the present invention can be widely used in various fields requiring antiviral properties.
  • the agent of the present invention can be used in various fields such as industry, cleaning, medical care, food, beverages, and daily necessities.
  • the use of the agent of the present invention is mainly divided into a use applied to a living body and a use applied to an article described later.
  • Applications applied to living organisms include, for example, pharmaceuticals, cosmetics, food compositions (including health foods, health promoters, dietary supplements (supplements, etc.)), beverage compositions, food additives, beverages. Examples include additives, disinfectants, cleaning agents and the like.
  • the application target in this case is not particularly limited, and examples thereof include various mammals such as humans, monkeys, mice, rats, dogs, cats, rabbits, pigs, horses, cows, sheep, goats, and deer.
  • the agent of the present invention By applying the agent of the present invention to a living body, it is possible to exert an antiviral effect at a site where the active ingredient comes into contact.
  • the form of the agent of the present invention is not particularly limited, and the form usually used in each application can be taken depending on the use of the agent of the present invention.
  • the use is pharmaceutical, for example, an injection, a drip, a mouthwash, an inhalant, a patch (a plaster, a tape such as a plaster (reservoir type, matrix type, etc.), a pap, a patch).
  • a plaster a tape such as a plaster (reservoir type, matrix type, etc.)
  • a pap a patch
  • Suitable for oral ingestion of including), rounds, granules, fine granules, powders, hard capsules, soft capsules, dry syrups, liquids (including drinks, suspensions and syrups), jelly, etc.
  • examples thereof include a formulation form (oral formulation form), a tube nutritional supplement, an enteral nutritional supplement, a nasal catheter preparation, an esophageal fistula catheter preparation, and a gastric fistula catheter preparation.
  • Examples of the form include liquids, gels, creams, ointments, sprays, sticks, etc. when the use is cosmetics.
  • liquid, gel or solid foods such as juices, soft drinks, tea, soups, soy milk and other beverages, salad oils, dressings, yogurt, jellies, puddings, sprinkles, etc.
  • dairy products eg, powder, liquid, gel, solid, etc.
  • bread e.g., cookies, etc.
  • a health enhancer, a dietary supplement supplied, etc.
  • it includes, for example, tablets (intraoral disintegrating tablets, chewable tablets, effervescent tablets, troches, jelly-like drops, etc.). ), Rounds, granules, fine granules, powders, hard capsules, soft capsules, dry syrups, liquids (including suspensions and syrups), jelly and the like.
  • a disinfectant or cleaning agent for example, a liquid (solution, emulsion, suspension, spray, etc.), a semi-solid (gel, cream, paste, etc.), a solid (tablet, particulate agent, etc.) It can take any form such as a capsule, a film, a kneaded product, a molten solid, a waxy solid, an elastic solid, etc.).
  • dentifrice dentifrice, liquid dentifrice, liquid dentifrice, powdered dentifrice, etc.
  • mouthwash coating agent
  • patch mouth refreshing agent
  • food For example, chewing gum, confectionery, candy, toothpaste, film, troche, etc.
  • a spray-type nasal drop agent, a nasal irrigation agent and the like can be mentioned.
  • soaps, body soaps, shampoos, conditioners, sprays and the like can be mentioned.
  • the agent of the present invention may further contain other components, if necessary.
  • the other components are not particularly limited as long as they are components that can be blended in, for example, pharmaceuticals, cosmetics, disinfectants, cleaning agents, etc., but for example, bases, carriers, solvents, dispersants, emulsifiers, buffers, etc. Stabilizers, excipients, binders, disintegrants, lubricants, thickeners, moisturizers, colorants, fragrances, chelating agents and the like can be mentioned.
  • the buffering agent is not particularly limited, and an appropriate buffering agent that is acceptable can be adopted depending on the intended use.
  • Preferred examples include a phosphate buffer solution and an acetic acid buffer solution.
  • the content of the active ingredient of the agent of the present invention depends on the type, use, mode of use, application target, state of application target, etc. of the active ingredient, and is not limited, but is, for example, 0.000001 to 100% by weight. It can be preferably 0.01 to 50% by weight.
  • the amount of the agent of the present invention applied is not particularly limited as long as it is an effective amount that exerts a desired effect, and is usually 0.1 to 0.1 per day as the weight of the active ingredient. 1000 mg / kg body weight.
  • the above dose is preferably administered once a day or in 2 to 3 divided doses, and may be appropriately increased or decreased depending on the age, pathological condition, and symptoms.
  • Applications applied to articles examples include disinfectants, detergents and the like.
  • the application target in this case is not particularly limited, and examples thereof include industrial products and raw materials thereof used in various fields.
  • articles include masks, face masks, gloves and the like.
  • OA equipment home appliances, air conditioning equipment, vacuum cleaners, desks, chairs, sofas, benches, windows, leather, handles, seats, automatic ticket gates, automatic ticket vending machines, vending machines, doors, fences, handrails, tableware, Cooking utensils, packaging films, packaging bags, bottles, bottles, packaging packs, sinks, toilet bowls, stationery, books, shelves, toothbrushes, mirrors, air conditioning filters, coats, jackets, trousers, skirts, shirts, knit shirts, blouses, sweaters, Cardigan, nightwear, underwear, underwear, diapers, supporters, socks, tights, stockings, hats, scarves, mufflers, scarves, stalls, clothes linings, clothes cores, clothes batting, work clothes, uniforms, for school children Examples include clothing such as uniforms, curtains, ami doors, duvets, cotton duvets, duvet covers, pillowcases, sheets, mats, carpets, towels, handkerchiefs, wall cloths,
  • the agent of the present invention By applying the agent of the present invention to an article, it is possible to exert an antiviral effect at a site where the active ingredient comes into contact.
  • the site where the active ingredient comes into contact is not limited to the site on the article, but also includes the site in the living body when the article is applied to a living body or the like.
  • the dosage form of the agent of the present invention is not particularly limited and can be appropriately selected according to its intended use.
  • the dosage form include liquids such as liquids, emulsions, suspensions, dispersants, sprays and aerosols; solid or semi-solids such as wettable powders, powders, granules, fine granules and flowables. Be done. It can be applied or coated on various articles.
  • the agent of the present invention may further contain other components, if necessary.
  • the other components are not particularly limited as long as they are components that can be blended in, for example, cleaning agents and disinfectants for articles, but are not particularly limited, and are, for example, bases, carriers, solvents, dispersants, emulsifiers, buffers, and stabilizers. , Excipients, binders, disintegrants, lubricants, thickeners, moisturizers, colorants, fragrances, chelating agents and the like.
  • the buffering agent is not particularly limited, and an appropriate buffering agent that is acceptable can be adopted depending on the intended use.
  • Preferred examples include a phosphate buffer solution and an acetic acid buffer solution.
  • the content of the active ingredient of the agent of the present invention depends on the type, use, mode of use, application target, state of application target, etc. of the active ingredient, and is not limited, but is, for example, 0.000001 to 100% by weight. It can be preferably 0.001 to 50% by weight.
  • Test example 1 Evaluation test of antiviral effect 1 ⁇ Preparation of sample solution> Theasinensin A sample solution Theasinensin A was dissolved in sterile filtered water to 100 mM. The treatment was carried out in a constant temperature bath at 78 ° C. for several minutes. A 100 mM sample solution was further adjusted to 2 mM with filtered sterile water, filtered with 0.45 ⁇ m cellulose acetate, and then prepared with sterile water at concentrations of 400 and 80 ⁇ M.
  • EGCG sample solution 1 EGCG (-)-Epigallocatechin Gallate was lysed in DMSO to 100 mM. A 100 mM sample solution was further adjusted to 2 mM with filtered sterile water, filtered with 0.45 ⁇ m cellulose acetate, and then prepared with sterile water at concentrations of 400 and 80 ⁇ M.
  • EGCG sample liquid 2 EGCG (-)-Epigallocatechin Gallate was dissolved in sterile filtered water to 100 mM. The treatment was carried out in a constant temperature bath at 78 ° C. for several minutes. A 100 mM sample solution was further adjusted to 2 mM with filtered sterile water, filtered with 0.45 ⁇ m cellulose acetate, and then prepared with sterile water at concentrations of 400 and 80 ⁇ M.
  • Theaflavin di-gallate sample solution Theaflavin 3,3'-di-O -gallate was dissolved in sterile filtered water to 100 mM. The treatment was carried out in a constant temperature bath at 78 ° C. for several minutes. A 100 mM sample solution was further adjusted to 2 mM with filtered sterile water, filtered with 0.45 ⁇ m cellulose acetate, and then prepared with sterile water at concentrations of 400 and 80 ⁇ M.
  • ⁇ Test protocol> Add 20 ⁇ l of serum-free (SF) 2 X DMEM to 20 ⁇ l of sample solution or sterile water at each concentration (2000, 400, 80 ⁇ M), adjust the osmotic pressure, and immediately perform virus solution (1.5 X 10 ⁇ 6 TCID 50 ). / 50 ⁇ l) were added simultaneously, 40 ⁇ l each (sample concentrations were 500, 100, 20, 0 ⁇ M, respectively). After 1 minute, it was immediately diluted in 10 steps with SF DMEM. The supernatant was removed from VeroE6 / TMPRSS2 cells cultured on a 96-well plate, and 50 ⁇ l of each diluted solution was added.
  • SF serum-free
  • FBS DMEM 0.5% FBS DMEM was added at 100 ⁇ l / well, excluding the virus solution, and the cells were cultured in 37 ° C. and 5% CO 2 /95% air for 3 days. After adding 100 ⁇ L / well of glutaraldehyde and fixing for 30 minutes, the cells were stained with crystal violet, CPE (cytopathic effect) was observed, and TCID 50/50 ⁇ L was calculated by the Reed-Muench method.
  • Test example 2 Evaluation test of antiviral effect 2 ⁇ Preparation of sample solution> Theasinensin A was dissolved in sterile filtered water to 100 mM. The treatment was carried out in a constant temperature bath at 78 ° C. for several minutes. A 100 mM solution was further adjusted to 1 mM with filtered sterile water, and then filtered with 0.45 ⁇ m cellulose acetate to obtain a sample solution.
  • ⁇ Mix protocol> After adjusting the osmotic pressure by adding an equal amount of serum-free (SF) 2X DMEM to the sample solution, it was diluted in two steps with SF DMEM (MS) and used immediately. 10 ⁇ l of SARS-CoV-2 (1.5 X 10 ⁇ 6/50 ⁇ l) was added to 100 ⁇ l of Sample solution of each concentration or SF DMEM (MS), and the mixture was allowed to stand at room temperature for several minutes.
  • SF serum-free
  • MS SF DMEM
  • the supernatant was removed from a 96-well plate in which Vero E6 / TMPRSS2 cells were sown at 5 X 10 ⁇ 4/100 ⁇ l / well and cultured for 15 hours the day before, and 50 ⁇ l of the above virus / sample solution was added (MOI 3). After adsorption for 1h, the virus solution was removed, MS was added at 100 ⁇ l / well, and the cells were cultured for 30 hours. The viability of the cells was quantified by the following method.
  • ⁇ Method for quantifying cell Viability> Medium was removed from the Plate and washed with PBS. 20% of Cell Count Reagent SF (Nacalai) was mixed with phenol red-free medium, 50 ⁇ l / well was added to the cells, and the cells were cultured for 50 minutes. As a blank, a well in which only the reagent mixture was added to the well in which the cells were not cultured was also prepared. After completion of the reaction, 20 ⁇ l / well of 10% SDS was added to inactivate the virus remaining in the well. The absorbance at a wavelength of 450 nm was measured with a plate reader. The measurement was performed with tetraplicate.
  • Figure 2 shows the result of ⁇ Post protocol>. Compared with the cells to which Theasinensin A was not added, the cells to which Theasinensin A was added after the infection suppressed the decrease in viability due to the virus infection. Treatment of cells with Theasinensin A after infection could attenuate viral infection.
  • Figure 3 shows the result of ⁇ Mix protocol>. Compared to viruses without Theasinensin A, viruses with Theasinensin A added before infection and during adsorption to cells do not reduce the viability of cells after infection. Treatment of SARS-CoV-2 with Theasinensin A was able to reduce infectivity.
  • Test example 3 Evaluation test of antiviral effect 3 The outline of the method of this test is shown in FIG. VeroE6 / TMPRSS2 cells were seeded on a 24-well plate at 2.5x10 ⁇ 5/500 ⁇ l / well and cultured for 24 hours. The supernatant was removed from the cells, SARS-CoV-2 was added at 1.25x10 6 TCID 50/100 ⁇ L, and the cells were adsorbed at 37 C for 1 h, and then the virus solution was removed. EGCG dissolved in water or DMSO was diluted with 0.5% FBS DMEM (MS), added at 500 ⁇ l / well to 250 ⁇ M or 25 ⁇ M or 0 ⁇ M, and cultured for 16 hours.
  • MS FBS DMEM
  • ⁇ TCID 50 Assay> Day -1 Vero E6 / TMPRSS2 cells were seeded on a 96-well plate at 5.0 x 10 4 cells / 100 ⁇ L.
  • the medium is DMEM medium supplemented with 0.5% fetal bovine serum. Incubated for 24 hours at 37 ° C., 5% CO 2 / 95% air.
  • primers and probes The sequence of primers and probes is as follows.
  • the temperature conditions are as follows. 95 °C 20 seconds 95 °C 01 seconds 60 °C 20 seconds Number of cycles: 50 cycles Analysis was performed with StepOne Software (ABI) (software) using StepOnePlus (ABI) (instrument).

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Abstract

Provided is an anti-viral agent, and in particular, an anti-viral agent for coronaviruses such as SARS-CoV-2. This anti-viral agent contains a tea component.

Description

抗ウイルス剤Antiviral agent
　本発明は、抗ウイルス剤等に関する。 The present invention relates to an antiviral agent or the like.
　コロナウイルスは、コロナウイルス科のコロナウイルス亜科に属するウイルスの種であり、ヒトおよび動物に感染し、呼吸器、消化器、血管、または神経性の疾患を発症させるプラス鎖RNAウイルスである。コロナウイルスは、感染している何らかの宿主動物から伝播して、ヒトに対して大規模な伝染病を引き起こすことが可能である。コロナウイルスとしては、近年では、例えば、2002年及び2003年に流行したSARSコロナウイルス1（SARS-CoV-1）、及び中東呼吸器症候群コロナウイルス（MERS-CoV）が挙げられる。最近では、SARSコロナウイルス2（SARS-CoV-2）の世界的な流行が起こり、治療技術が確立されていないことから、医療、経済等の多方面に亘って甚大な被害が続いている。 Coronavirus is a species of virus belonging to the coronavirus subfamily of the coronavirus family, and is a plus-strand RNA virus that infects humans and animals and causes respiratory, digestive, vascular, or neurological diseases. Coronavirus can be transmitted from any infected host animal and cause a large-scale infectious disease in humans. Examples of coronaviruses include SARS coronavirus 1 (SARS-CoV-1), which was prevalent in 2002 and 2003, and Middle East respiratory syndrome coronavirus (MERS-CoV). Recently, a worldwide epidemic of SARS coronavirus 2 (SARS-CoV-2) has occurred, and since the treatment technology has not been established, serious damage continues in various fields such as medical care and economy.
　本発明は、抗ウイルス剤、特にSARS-CoV-2等のコロナウイルスに対する抗ウイルス剤を提供することを課題とする。 An object of the present invention is to provide an antiviral agent, particularly an antiviral agent against a coronavirus such as SARS-CoV-2.
　本発明者は上記課題に鑑みて鋭意研究を進めた結果、茶成分、特にカテキン類又はカテキン酸化重合物を含有する、抗ウイルス剤、であれば、上記課題を解決できることを見出した。本発明者は、この知見に基づいてさらに研究を進めた結果、本発明を完成させた。即ち、本発明は、下記の態様を包含する。 As a result of diligent research in view of the above problems, the present inventor has found that the above problems can be solved if it is an antiviral agent containing a tea component, particularly catechins or catechin oxidation polymers. The present inventor has completed the present invention as a result of further research based on this finding. That is, the present invention includes the following aspects.
　項１．　茶成分を含有する、抗ウイルス剤。 Item 1. An antiviral agent containing tea ingredients.
　項２．　前記茶成分がポリフェノール類である、項１に記載の抗ウイルス剤。 Item 2. Item 2. The antiviral agent according to Item 1, wherein the tea component is polyphenols.
　項３．　前記ポリフェノール類がカテキン類又はカテキン酸化重合物類である、項２に記載の抗ウイルス剤。 Item 3. Item 2. The antiviral agent according to Item 2, wherein the polyphenols are catechins or catechin oxidation polymers.
　項４．　前記カテキン類がガレート型カテキン類である、項３に記載の抗ウイルス剤。 Item 4. Item 3. The antiviral agent according to Item 3, wherein the catechins are gallate-type catechins.
　項５．　前記カテキン酸化重合物類がテアシネンシン類又はテアフラビン類である、項３に記載の抗ウイルス剤。 Item 5. Item 3. The antiviral agent according to Item 3, wherein the catechin oxide polymers are theacinencins or theaflavins.
　項６．　ウイルス感染抑制、ウイルスの細胞感染力価低下、ウイルスによる細胞死の抑制、及びウイルス不活化からなる群より選択される少なくとも１種に用いるための、項１～５のいずれかに記載の抗ウイルス剤。 Item 6. Item 2. The antivirus according to any one of Items 1 to 5 for use in at least one selected from the group consisting of suppression of virus infection, reduction of virus cell infection titer, suppression of cell death by virus, and virus inactivation. Agent.
　項７．　前記ウイルスがコロナウイルスである、項１～６のいずれかに記載の抗ウイルス剤。 Item 7. Item 2. The antiviral agent according to any one of Items 1 to 6, wherein the virus is a coronavirus.
　項８．　前記ウイルスがSARS-CoV-2である、項１～７のいずれかに記載の抗ウイルス剤。 Item 8. Item 2. The antiviral agent according to any one of Items 1 to 7, wherein the virus is SARS-CoV-2.
　項９．　生体に適用するために用いられる、項１～８のいずれかに記載の抗ウイルス剤。 Item 9. Item 2. The antiviral agent according to any one of Items 1 to 8, which is used for application to a living body.
　項１０．　医薬、化粧品、飲料組成物、食品組成物、食品添加剤、消毒剤又は洗浄剤である、項９に記載の抗ウイルス剤。 Item 10. Item 9. The antiviral agent according to Item 9, which is a pharmaceutical, cosmetics, beverage composition, food composition, food additive, disinfectant or detergent.
　項１１．　COVID-19の予防又は治療剤である、項９又は１０に記載の抗ウイルス剤。 Item 11. Item 9. The antiviral agent according to Item 9 or 10, which is a preventive or therapeutic agent for COVID-19.
　項１２．　物品に適用するために用いられる、項１～８のいずれかに記載の抗ウイルス剤。 Item 12. Item 2. The antiviral agent according to any one of Items 1 to 8, which is used for applying to articles.
　項１３．　消毒剤又は洗浄剤である、項１２に記載の抗ウイルス剤。 Item 13. Item 12. The antiviral agent according to Item 12, which is a disinfectant or a cleaning agent.
　項１４．　茶成分を生体又は物品に適用することを含む、抗ウイルス方法。 Item 14. An antiviral method involving the application of tea ingredients to living organisms or articles.
　項１５．　ウイルス感染症を有する対象に茶成分を摂取させることを含む、抗ウイルス方法。 Item 15. An antiviral method that involves ingesting tea ingredients in a subject with a viral infection.
　項１６．　抗ウイルス剤としての使用のための、茶成分。 Item 16. Tea ingredient for use as an antiviral agent.
　項１７．　茶成分の、抗ウイルス剤の製造のための使用。 Item 17. Use of tea ingredients for the production of antiviral agents.
　項１８．　茶成分の、抗ウイルス剤としての使用。 Item 18. Use of tea ingredients as an antiviral agent.
　本発明によれば、抗ウイルス剤、特にSARS-CoV-2等のコロナウイルスに対する抗ウイルス剤を提供することができる。 According to the present invention, it is possible to provide an antiviral agent, particularly an antiviral agent against a coronavirus such as SARS-CoV-2.
試験例1の結果を示す。縦軸は、TCID50/50μLを示す。横軸に、サンプル名及びそのウイルス接触時濃度を示す。横軸中、Controlは、サンプル液に代えて滅菌水を使用した場合を示す。The results of Test Example 1 are shown. The vertical axis shows TCID 50/50 μL. The horizontal axis shows the sample name and its concentration at the time of contact with the virus. In the horizontal axis, Control indicates the case where sterile water is used instead of the sample solution. 試験例2のPost protocol結果を示す。縦軸は、クリスタルバイオレット染色後のOD値を示す。横軸は、サンプル液の使用時の（ウイルス／細胞との混合前の）濃度を示す。The Post protocol result of Test Example 2 is shown. The vertical axis shows the OD value after crystal violet staining. The horizontal axis shows the concentration of the sample solution at the time of use (before mixing with virus / cells). 試験例2のMix protocol結果を示す。縦軸は、クリスタルバイオレット染色後のOD値を示す。横軸は、サンプル液の使用時の（ウイルス／細胞との混合前の）濃度を示す。The Mix protocol result of Test Example 2 is shown. The vertical axis shows the OD value after crystal violet staining. The horizontal axis shows the concentration of the sample solution at the time of use (before mixing with virus / cells). 試験例3の方法の概略を示す。The outline of the method of Test Example 3 is shown. 試験例3のTCID50アッセイの結果を示す。縦軸は、TCID50/50μLを示す。横軸に、サンプル名及びそのウイルス接触時濃度を示す。横軸中、Controlは、サンプル液に代えて滅菌水を使用した場合を示す。The results of the TCID 50 assay of Test Example 3 are shown. The vertical axis shows TCID 50/50 μL. The horizontal axis shows the sample name and its concentration at the time of contact with the virus. In the horizontal axis, Control indicates the case where sterile water is used instead of the sample solution. 試験例3のqRT-PCRの結果を示す。縦軸は、ウイルスRNA量の相対値を示す。横軸に、サンプル名及びそのウイルス接触時濃度を示す。横軸中、Controlは、サンプル液に代えて滅菌水を使用した場合を示す。The results of qRT-PCR of Test Example 3 are shown. The vertical axis shows the relative value of the amount of viral RNA. The horizontal axis shows the sample name and its concentration at the time of contact with the virus. In the horizontal axis, Control indicates the case where sterile water is used instead of the sample solution.
　本明細書中において、「含有」及び「含む」なる表現については、「含有」、「含む」、「実質的にからなる」及び「のみからなる」という概念を含む。 In the present specification, the expressions "contains" and "contains" include the concepts of "contains", "contains", "substantially consists" and "consists only".
　本発明は、その一態様において、茶成分を含有する、抗ウイルス剤、及びカテキン酸化重合物を含有する、抗ウイルス剤（これらをまとめて、本明細書において、「本発明の剤」と示すこともある。）に関する。以下、これについて説明する。 In one aspect of the present invention, an antiviral agent containing a tea component and an antiviral agent containing a catechin oxidative polymer (these are collectively referred to as "the agent of the present invention" in the present specification. Sometimes.). This will be described below.
　1．有効成分
　有効成分は、茶成分である。 1. 1. Active ingredient The active ingredient is a tea ingredient.
　茶成分は、緑茶・ウーロン茶・紅茶・後発酵茶から得られる成分を包含する（『茶の機能：生体機能の新たな可能性』、村松敬一郎他（編）、学会出版センター、２００２年）が、抽出により得られる成分を好適に用いることができる。茶に含まれる成分又は当該成分由来の成分である限り特に制限されず、単一化合物、及び複数の化合物の混合物のいずれも包含する。 Tea ingredients include ingredients obtained from green tea, oolong tea, black tea, and post-fermented tea ("Tea Function: New Possibility of Biological Functions", Keiichiro Muramatsu et al. (Ed.), Academic Publishing Center, 2002). , The components obtained by extraction can be preferably used. It is not particularly limited as long as it is a component contained in tea or a component derived from the component, and includes either a single compound or a mixture of a plurality of compounds.
　茶は、茶用植物から抽出して得られたものである限り、特に制限されない。 Tea is not particularly limited as long as it is obtained by extracting from a tea plant.
　茶用植物としては、好ましくはツバキ属（Camellia）植物が挙げられ、特に好ましくはチャノキ（Camellia sinensis）が挙げられる。 Examples of the tea plant preferably include Camellia plants, and particularly preferably Camellia sinensis.
　抽出に供される茶用植物の部位としては、特に制限されず、例えば葉、枝等が挙げられる。これらの中でも、好ましくは葉が挙げられる。 The part of the tea plant used for extraction is not particularly limited, and examples thereof include leaves and branches. Among these, leaves are preferably mentioned.
　抽出に供される茶用植物は、例えば、収穫後に熱処理（例えば蒸す、炒める、火で炙る、天日干し等）等により酵素を不活性化させた不発酵のものであってもよいし、酵素の不活性化の強度を弱め或いはそのタイミングを遅らせること等により酵素によりある程度発酵（半発酵）させたものであってもよいし、酵素の不活性化の強度を弱め或いは酵素を不活性化させないこと等により酵素により完全に発酵させたものであってもよいし、乳酸菌等の微生物を加えて発酵させたものであってもよい。 The tea plant used for extraction may be, for example, an unfermented one in which the enzyme is inactivated by heat treatment (for example, steaming, frying, roasting on fire, sun-drying, etc.) after harvesting, or the enzyme. It may be fermented (semi-fermented) to some extent by an enzyme by weakening the inactivation intensity of the enzyme or delaying the timing thereof, or it may not weaken the inactivation intensity of the enzyme or inactivate the enzyme. It may be completely fermented by an enzyme or the like, or it may be fermented by adding a microorganism such as lactic acid bacteria.
　抽出に供される茶用植物として、好ましくは茶葉が挙げられる。茶葉としては、例えば抹茶の茶葉、煎茶の茶葉、ほうじ茶の茶葉、新茶の茶葉、紅茶の茶葉、プーアール茶の茶葉、ウーロン茶の茶葉等が挙げられる。これら以外にも、茶葉としては、上記以外の緑茶（例えば玉露、番茶、玄米茶等）の茶葉、白茶の茶葉、黄茶の茶葉、黒茶の茶葉、花茶の茶葉等が挙げられる。茶葉として、好ましくは抹茶の茶葉、煎茶の茶葉、ほうじ茶の茶葉、新茶の茶葉、紅茶の茶葉、プーアール茶の茶葉、ウーロン茶の茶葉等が挙げられ、より好ましくは抹茶の茶葉、煎茶の茶葉、ほうじ茶の茶葉、紅茶の茶葉、ウーロン茶の茶葉等が挙げられ、特に好ましくは抹茶の茶葉、ほうじ茶の茶葉、紅茶の茶葉等が挙げられる。 The tea plant used for extraction is preferably tea leaves. Examples of the tea leaves include matcha tea leaves, roasted tea leaves, roasted tea leaves, new tea leaves, black tea leaves, pouer tea leaves, oolong tea leaves and the like. In addition to these, examples of tea leaves include green tea leaves (for example, Tamaro, Bancha, brown rice tea, etc.), white tea leaves, yellow tea leaves, black tea leaves, flower tea leaves, and the like. Examples of the tea leaves include matcha tea leaves, roasted tea leaves, roasted tea leaves, new tea leaves, tea leaves, pouer tea leaves, oolong tea leaves, and the like, and more preferably matcha tea leaves, roasted tea leaves, and roasted tea leaves. Examples thereof include tea leaves of tea, tea leaves of tea, tea leaves of oolong tea, and particularly preferably tea leaves of matcha, tea leaves of roasted tea, and tea leaves of tea.
　抽出に供される茶用植物は、必要に応じて裁断しておくことが好ましい。また、必要に応じて、蒸熱、粗揉、揉捻、中揉、精揉、乾燥、圧搾等の前処理を行うこともできる。 It is preferable to cut the tea plants used for extraction as necessary. Further, if necessary, pretreatments such as steaming, rough kneading, kneading, medium kneading, fine kneading, drying, and squeezing can be performed.
　茶用植物は1種単独でもよいし、2種以上の組合せであってもよい。 The tea plant may be one kind alone or a combination of two or more kinds.
　抽出溶媒は、特に制限されない。抽出溶媒としては、水；メタノール、エタノール、プロパノール、ブタノール等の低級1価アルコール；グリセリン、プロピレングリコール、1,3－ブチレングリコール等の液状多価アルコール；アセトン等のケトン類；エチルエーテル等のエーテル類；酢酸メチル、酢酸エチル、酢酸プロピル、酢酸ブチル等のエステル類；超臨界二酸化炭素等が挙げられる。抽出溶媒は1種単独でもよいし、2種以上の組合せであってもよい。抽出溶媒として、好ましくは水を含有（例えば50質量％以上、70質量％以上、80質量％以上、90質量％以上、又は95質量％以上含有）する溶媒が挙げられ、特に好ましくは水が挙げられる。 The extraction solvent is not particularly limited. Extraction solvents include water; lower monohydric alcohols such as methanol, ethanol, propanol and butanol; liquid polyhydric alcohols such as glycerin, propylene glycol and 1,3-butylene glycol; ketones such as acetone; ethers such as ethyl ether. Kind: Esters such as methyl acetate, ethyl acetate, propyl acetate, butyl acetate; supercritical carbon dioxide and the like. The extraction solvent may be one kind alone or a combination of two or more kinds. Examples of the extraction solvent include a solvent containing water (for example, 50% by mass or more, 70% by mass or more, 80% by mass or more, 90% by mass or more, or 95% by mass or more), and water is particularly preferable. Be done.
　抽出時の溶媒の温度は、特に制限されないが、例えば4～100℃、好ましくは50～100℃、より好ましくは60～100℃である。温度は、茶用植物の種類等に応じて、適宜設定することもできる。 The temperature of the solvent at the time of extraction is not particularly limited, but is, for example, 4 to 100 ° C, preferably 50 to 100 ° C, and more preferably 60 to 100 ° C. The temperature can be appropriately set according to the type of tea plant and the like.
　抽出溶媒の使用量は、特に制限されないが、茶用植物1質量部に対して、例えば1～2000質量部、5～1000質量、又は10～500質量部である。使用量は、茶用植物の種類等に応じて、適宜設定することもできる。 The amount of the extraction solvent used is not particularly limited, but is, for example, 1 to 2000 parts by mass, 5 to 1000 parts by mass, or 10 to 500 parts by mass with respect to 1 part by mass of the tea plant. The amount used can be appropriately set according to the type of tea plant and the like.
　抽出時間は、抽出方法、溶媒、温度等によって異なり、特に制限されない。抽出時間は、例えば10秒間～1時間、又は30秒間～10分間である。抽出時間は、茶用植物の種類等に応じて、適宜設定することもできる。 The extraction time varies depending on the extraction method, solvent, temperature, etc., and is not particularly limited. The extraction time is, for example, 10 seconds to 1 hour, or 30 seconds to 10 minutes. The extraction time can be appropriately set according to the type of tea plant and the like.
　抽出後は、必要に応じて、抽出残渣を除去することができる。除去する方法としては、特に制限されず、例えば自然落下、遠心分離、ろ過等の方法を1種又は2種以上を組合わせて採用することができる。 After extraction, the extraction residue can be removed as needed. The method for removing is not particularly limited, and for example, a method such as free fall, centrifugation, or filtration can be adopted by one type or a combination of two or more types.
　茶成分の性状は、特に制限されず、例えば液状、スラリー状、ペースト状、固形状、粉末状等であり得る。茶抽出物は、抽出液そのものであってもよいし、抽出液の濃縮物（乾燥物も包含する）であってもよいし、これらの混合物であってもよい。 The properties of the tea component are not particularly limited and may be, for example, liquid, slurry, paste, solid, powder or the like. The tea extract may be the extract itself, a concentrate of the extract (including a dried product), or a mixture thereof.
　本発明の茶成分としては、ポリフェノール類、特にカテキン類やカテキン酸化重合物を好適に用いることができる。 As the tea component of the present invention, polyphenols, particularly catechins and catechin oxidation polymers can be preferably used.
　本発明におけるカテキン類は、フラバン－３－オールに複数のヒドロキシ基が置換してなる誘導体又はその芳香族カルボン酸（例えば没食子酸）エステルである限り、特に限定されない。具体的には、『茶の機能：生体機能の新たな可能性』（村松敬一郎他（編）、学会出版センター、２００２年）第３５～４１頁に記載されるものを包含するものであるが、例えば、エピガロカテキンガレート（ＥＧＣＧ）、エピカテキンガレート（ＥＧＣ）、ガロカテキンガレート（ＧＣＧ）、カテキンガレート（ＣＧ）のガレート型カテキン類や、エピガロカテキン（ＥＧＣ）、エピカテキン（ＥＣ）、ガロカテキン（ＧＣ）、カテキン（Ｃ）の非ガレート型カテキン類をその有効成分として挙げることができる。 The catechins in the present invention are not particularly limited as long as they are derivatives in which flavan-3-ols are substituted with a plurality of hydroxy groups or aromatic carboxylic acid (for example, gallic acid) esters thereof. Specifically, it includes those described in "Functions of Tea: New Possibilities of Biological Functions" (Keiichiro Muramatsu et al. (Ed.), Society Publishing Center, 2002), pp. 35-41. For example, epigallocatechin gallate (EGCG), epicatechin gallate (EGC), galocacatechin gallate (GCG), gallate-type catechins of catechin gallate (CG), epigallocatechin (EGC), epicatechin (EC), Galocatechin (GC) and non-gallate-type catechins of catechin (C) can be mentioned as the active ingredient thereof.
　また、本発明におけるカテキン酸化重合物は、カテキンから酸化を経て生成される重合物である限りにおいて特に制限されないが、例えばテアシネンシン類、ウーロンテアニン類、プロアントシアニジン類、アッサミカイン類、ウーロンホモビスフラバン類、加水分解型タンニン、テアフラビン類、テアフラガリン類等を挙げることができ（前記書籍を参照）、好ましくはテアシネンシン類、テアフラビン類等を挙げることができ、なかでもテアシネンシンＡ、テアフラビンジガレートを最も好適に用いることができる。 The catechin oxidation polymer in the present invention is not particularly limited as long as it is a polymer produced from catechin through oxidation, but for example, theaflavins, oolontheanins, proanthocyanidins, assamicines, and oolonhomobisflavans. , Hydrolysable tannins, theaflavins, theaflavins, etc. (see the above book), preferably theacinencins, theaflavins, etc., among which theacinencin A and theaflavin digarates are most preferable. Can be used.
　テアシネンシン類は、カテキン類がB環同士で結合した二量体であり、典型的には以下の一般式： Teasinencins are dimers in which catechins are bound to each other in the B ring, and are typically the following general formula:
Figure JPOXMLDOC01-appb-C000001
 ［式中：R1及びR2は同一又は異なって、水素原子又はガロイル基を示す。］
で表される化合物である。
Figure JPOXMLDOC01-appb-C000001
 [In the formula: R 1 and R 2 are the same or different and indicate a hydrogen atom or a galloyl group. ]
It is a compound represented by.
　テアシネンシン類として、より具体的には、例えば、一般式（Ia）又は（Ib）： More specifically, as the teasinencins, for example, the general formula (Ia) or (Ib) :.
Figure JPOXMLDOC01-appb-C000002
 ［式中：R1及びR2は前記に同じである。］
で表される化合物、さらに具体的にはテアシネンシンA（Ia：R1=R2=ガロイル基）、テアシネンシンB（Ia：R1=ガロイル基、R2＝水素原子）、テアシネンシンC（Ia：R1＝R2＝水素原子）、テアシネンシンD（Ib：R1=R2=ガロイル基）、テアシネンシンE（Ib：R1＝R2＝水素原子）等が挙げられる。これらの中でも、特に好ましくは、テアシネンシンAが挙げられる。
Figure JPOXMLDOC01-appb-C000002
 [In the formula: R 1 and R 2 are the same as above. ]
Compounds represented by, more specifically, teasinencin A (Ia: R 1 = R 2 = galloyl group), teasinencin B (Ia: R 1 = galloyl group, R 2 = hydrogen atom), teasinencin C (Ia: R). 1 = R 2 = hydrogen atom), teasinencin D (Ib: R 1 = R 2 = galloyl group), teasinencin E (Ib: R 1 = R 2 = hydrogen atom) and the like. Among these, teasinencin A is particularly preferable.
　テアフラビン類としては、例えばテアフラビン（非ガレート型テアフラビン）の他、テアフラビン-3-モノガレート、テアフラビン-3’-モノガレート、テアフラビン-3,3’-ジガレート等のガレート基を有するエステル型テアフラビン（ガレート型テアフラビン類）が挙げられる。これらの中でも、好ましくはガレート型テアフラビン類が挙げられ、より好ましくはテアフラビン-3,3’-ジガレートが挙げられる。 Examples of theaflavins include theaflavins (non-gallate type theaflavins), theaflavins-3-monogallate, theaflavin-3'-monogallate, theaflavin-3,3'-digalate and other ester-type theaflavins (gallate-type theaflavins). Kind). Among these, gallate-type theaflavins are preferable, and theaflavins-3,3'-digalate are more preferable.
　また、前記茶成分はいずれも誘導体であってよく、例えば、カテキン酸化重合物の誘導体、テアシネンシンの誘導体、テアシネンシン類の誘導体を挙げることができる。 Further, any of the tea components may be a derivative, and examples thereof include a derivative of a catechin oxide polymer, a derivative of teacinencin, and a derivative of teasinencins.
　茶成分は、茶から得て（必要に応じて酸化処理により生成して）用いてもよいし、茶以外の植物や食品などから得て用いてもよい。それらの場合、何らかの濃縮、および・または分画、および・または精製等のプロセスを加えて得てもよい。また、茶成分は合成して用いてもよい。 The tea component may be obtained from tea (generated by oxidation treatment if necessary) or may be obtained from plants or foods other than tea. In those cases, it may be obtained by adding some process such as concentration and / or fractionation and / or purification. Further, the tea component may be synthesized and used.
　有効成分は、1種単独であってもよいし、2種以上の組合わせであってもよい。 The active ingredient may be one kind alone or a combination of two or more kinds.
　2．用途
　本発明の剤の対象ウイルスとしては、特に制限されない。ウイルスとしては、例えばインフルエンザウイルス（例えばA型、B型等）、風疹ウイルス、エボラウイルス、コロナウイルス、麻疹ウイルス、水痘・帯状疱疹ウイルス、ムンプスウイルス、アルボウイルス、RSウイルス、SARSウイルス、肝炎ウイルス（例えば、B型肝炎ウイルス、C型肝炎ウイルス等）、黄熱ウイルス、エイズウイルス、狂犬病ウイルス、ハンタウイルス、デングウイルス、ニパウイルス、リッサウイルス等のエンベロープウイルス（エンベロープを有するウイルス）；　アデノウイルス、ノロウイルス、ロタウイルス、ヒトパピローマウイルス、ポリオウイルス、エンテロウイルス、コクサッキーウイルス、ヒトパルボウイルス、脳心筋炎ウイルス、ポリオウイルス、ライノウイルス等の非エンベロープウイルス（エンベロープを有さないウイルス）等が挙げられる。これらの中でも、コロナウイルスが特に好ましい。 2. Use The target virus of the agent of the present invention is not particularly limited. Examples of viruses include influenza virus (for example, type A, type B, etc.), ruin virus, Ebola virus, corona virus, measles virus, varicella / herpes zoster virus, mumps virus, arbovirus, RS virus, SARS virus, hepatitis virus (for example). For example, hepatitis B virus, hepatitis C virus, etc.), yellow fever virus, AIDS virus, mad dog disease virus, hunter virus, dengue virus, nipavirus, lissavirus and other enveloped viruses (enveloped viruses); adenovirus, norovirus, rotavirus. , Human papillomavirus, poliovirus, enterovirus, coxsackie virus, human parvovirus, encephalomyelitis virus, poliovirus, rhinovirus and other non-enveloped viruses (viruses without envelope) and the like. Of these, coronavirus is particularly preferred.
　コロナウイルスは、オルトコロナウイルス亜科に属するウイルスである。コロナウイルスとしては、アルファコロナウイルス属、ベータコロナウイルス属、ガンマコロナウイルス属、デルタコロナウイルス属等が挙げられ、これらの中でも、ベータコロナウイルス属が好ましい。ベータコロナウイルス属としては、SARS関連コロナウイルス（SARSr-CoV）、広コロナウイルスHKU1、MERSコロナウイルス等が挙げられ、これらの中でも、SARSr-CoVが好ましい。SARSr-CoVとしては、SARS-CoV-2、SARS-CoV-1等が挙げられ、これらの中でもSARS-CoV-2が好ましい。本発明の剤は、特にSARS-CoV-2に対して好適に使用することができる。 Coronavirus is a virus belonging to the subfamily Orthocoronavirus. Examples of the coronavirus include alpha coronavirus genus, beta coronavirus genus, gamma coronavirus genus, delta coronavirus genus, and the like, and among these, beta coronavirus genus is preferable. Examples of the beta coronavirus genus include SARS-related coronavirus (SARSr-CoV), broad coronavirus HKU1, and MERS coronavirus, and among these, SARSr-CoV is preferable. Examples of SARSr-CoV include SARS-CoV-2 and SARS-CoV-1, and among these, SARS-CoV-2 is preferable. The agent of the present invention can be particularly preferably used for SARS-CoV-2.
　本発明の剤によれば、ウイルスに対して抗ウイルス作用を発揮することができる。抗ウイルス作用としては、具体的には、ウイルス感染抑制作用、ウイルスの細胞感染力価低下作用、ウイルスによる細胞死を抑制する作用、ウイルス不活化作用、ウイルス増殖抑制作用、ウイルス出芽抑制作用、ウイルス抵抗性誘導作用等が挙げられる。本発明の剤は、ウイルス感染抑制、ウイルスの細胞感染力価低下剤、ウイルスによる細胞死の抑制、ウイルス不活化、ウイルス増殖抑制、ウイルス出芽抑制、ウイルス抵抗性誘導からなる群より選択される少なくとも1種に用いることができる。また、これらの作用により、コロナウイルス感染症（特に、COVID-19）の予防又は治療剤として使用することもできる。 According to the agent of the present invention, it can exert an antiviral action against a virus. Specifically, the antiviral action includes a virus infection suppressing action, a virus cell infecting titer lowering action, a virus-induced cell death suppressing action, a virus inactivating action, a virus growth suppressing action, a virus emergence suppressing action, and a virus. The resistance-inducing action and the like can be mentioned. The agent of the present invention is at least selected from the group consisting of virus infection suppression, virus cell infectivity-lowering agent, virus-induced cell death suppression, virus inactivation, virus growth suppression, virus germination suppression, and virus resistance induction. It can be used for one species. In addition, due to these actions, it can also be used as a prophylactic or therapeutic agent for coronavirus infections (particularly COVID-19).
　本発明の剤は、抗ウイルス性を要する各種分野において広く使用することができる。本発明の剤は、例えば工業、洗浄、医療、食品、飲料、日用品等の各種分野において使用することができる。本発明の剤の用途は、主に、生体に適用する用途と、後述の物品に適用する用途とに分けられる。 The agent of the present invention can be widely used in various fields requiring antiviral properties. The agent of the present invention can be used in various fields such as industry, cleaning, medical care, food, beverages, and daily necessities. The use of the agent of the present invention is mainly divided into a use applied to a living body and a use applied to an article described later.
　2-1．生体に適用する用途
　生体に適用する用途としては、例えば医薬、化粧品、食品組成物（健康食品、健康増進剤、栄養補助食品（サプリメントなど）を包含する）、飲料組成物、食品添加剤、飲料添加物、消毒剤、洗浄剤等が挙げられる。この場合の適用対象は特に限定されず、例えば、ヒト、サル、マウス、ラット、イヌ、ネコ、ウサギ、ブタ、ウマ、ウシ、ヒツジ、ヤギ、シカなどの種々の哺乳類動物などが挙げられる。 2-1. Applications applied to living organisms Applications applied to living organisms include, for example, pharmaceuticals, cosmetics, food compositions (including health foods, health promoters, dietary supplements (supplements, etc.)), beverage compositions, food additives, beverages. Examples include additives, disinfectants, cleaning agents and the like. The application target in this case is not particularly limited, and examples thereof include various mammals such as humans, monkeys, mice, rats, dogs, cats, rabbits, pigs, horses, cows, sheep, goats, and deer.
　本発明の剤を生体に適用することによって、有効成分が接触する部位において抗ウイルス作用を発揮することができる。 By applying the agent of the present invention to a living body, it is possible to exert an antiviral effect at a site where the active ingredient comes into contact.
　本発明の剤の形態は、特に限定されず、本発明の剤の用途に応じて、各用途において通常使用される形態をとることができる。 The form of the agent of the present invention is not particularly limited, and the form usually used in each application can be taken depending on the use of the agent of the present invention.
　形態としては、用途が医薬である場合は、例えば注射剤、点滴剤、うがい剤、吸入剤、貼付剤（プラスター剤、硬膏剤等のテープ剤（リザーバー型、マトリックス型等）、パップ剤、パッチ剤、マイクロニードル等）、軟膏剤、外用液剤（リニメント剤、ローション剤等）、スプレー剤（外用エアゾール剤、ポンプスプレー剤等、クリーム剤、ゲル剤、点眼剤、眼軟膏剤、点鼻剤、坐剤、直腸用半固形剤、注腸剤等の非経口摂取に適した製剤形態；　錠剤（口腔内側崩壊錠、咀嚼可能錠、発泡錠、トローチ剤、ゼリー状ドロップ剤、舌下錠などを含む）、丸剤、顆粒剤、細粒剤、散剤、硬カプセル剤、軟カプセル剤、ドライシロップ剤、液剤（ドリンク剤、懸濁剤、シロップ剤を含む）、ゼリー剤などの経口摂取に適した製剤形態（経口製剤形態）、経管栄養剤、経腸栄養剤、経鼻カテーテル剤、食道ろうカテーテル剤、胃ろうカテーテル剤などが挙げられる。 As for the form, when the use is pharmaceutical, for example, an injection, a drip, a mouthwash, an inhalant, a patch (a plaster, a tape such as a plaster (reservoir type, matrix type, etc.), a pap, a patch). Agents, microneedles, etc.), ointments, external liquids (liniment agents, lotions, etc.), sprays (external aerosols, pump sprays, etc., creams, gels, eye drops, eye ointments, nasal drops, etc.) Pharmaceutical form suitable for parenteral ingestion of suppositories, semi-solids for rectal, enema, etc .; tablets (intraoral disintegrating tablets, chewable tablets, effervescent tablets, troches, jelly-like drops, sublingual tablets, etc. Suitable for oral ingestion of (including), rounds, granules, fine granules, powders, hard capsules, soft capsules, dry syrups, liquids (including drinks, suspensions and syrups), jelly, etc. Examples thereof include a formulation form (oral formulation form), a tube nutritional supplement, an enteral nutritional supplement, a nasal catheter preparation, an esophageal fistula catheter preparation, and a gastric fistula catheter preparation.
　形態としては、用途が化粧品である場合は、例えば液剤、ジェル剤、クリーム剤、軟膏剤、スプレー剤、スティック剤等が挙げられる。 Examples of the form include liquids, gels, creams, ointments, sprays, sticks, etc. when the use is cosmetics.
　形態としては、用途が食品組成物の場合は、液状、ゲル状あるいは固形状の食品、例えばジュース、清涼飲料、茶、スープ、豆乳などの飲料、サラダ油、ドレッシング、ヨーグルト、ゼリー、プリン、ふりかけ、育児用粉乳、ケーキミックス、乳製品（例えば、粉末状、液状、ゲル状、固形状等）、パン、菓子（例えば、クッキー等）などが挙げられる。また、用途が食品添加剤、健康増進剤、栄養補助食品（サプリメントなど）などである場合は、例えば錠剤（口腔内側崩壊錠、咀嚼可能錠、発泡錠、トローチ剤、ゼリー状ドロップ剤などを含む）、丸剤、顆粒剤、細粒剤、散剤、硬カプセル剤、軟カプセル剤、ドライシロップ剤、液剤（懸濁剤、シロップ剤を含む）、ゼリー剤などが挙げられる。 In terms of form, when the application is a food composition, liquid, gel or solid foods such as juices, soft drinks, tea, soups, soy milk and other beverages, salad oils, dressings, yogurt, jellies, puddings, sprinkles, etc. Examples include milk powder for childcare, cake mixes, dairy products (eg, powder, liquid, gel, solid, etc.), bread, confectionery (eg, cookies, etc.). When the application is a food additive, a health enhancer, a dietary supplement (supplement, etc.), it includes, for example, tablets (intraoral disintegrating tablets, chewable tablets, effervescent tablets, troches, jelly-like drops, etc.). ), Rounds, granules, fine granules, powders, hard capsules, soft capsules, dry syrups, liquids (including suspensions and syrups), jelly and the like.
　形態としては、用途が消毒剤又は洗浄剤である場合は、例えば液体（溶液、乳液、懸濁液、スプレーなど）、半固体（ゲル、クリーム、ペーストなど）、固体（錠剤、粒子状剤、カプセル剤、フィルム剤、混練物、溶融固体、ロウ状固体、弾性固体など）などの任意の形態を採ることができる。例えば、口腔に適用する場合であれば、より具体的には、歯磨剤（練歯磨、液体歯磨、液状歯磨、粉歯磨など）、洗口剤、塗布剤、貼付剤、口中清涼剤、食品（例えば、チューインガム、錠菓、キャンディ、グミ、フィルム、トローチなど）などが挙げられる。また、鼻腔に適用する場合であれば、より具体的には、スプレー型点鼻剤、鼻うがい剤等が挙げられる。皮膚に適用する場合であれば、石鹸、ボディソープ、シャンプー、リンス、スプレー剤等が挙げられる。 In terms of form, when the application is a disinfectant or cleaning agent, for example, a liquid (solution, emulsion, suspension, spray, etc.), a semi-solid (gel, cream, paste, etc.), a solid (tablet, particulate agent, etc.) It can take any form such as a capsule, a film, a kneaded product, a molten solid, a waxy solid, an elastic solid, etc.). For example, when applied to the oral cavity, more specifically, dentifrice (dentifrice, liquid dentifrice, liquid dentifrice, powdered dentifrice, etc.), mouthwash, coating agent, patch, mouth refreshing agent, food ( For example, chewing gum, confectionery, candy, toothpaste, film, troche, etc.). Further, when applied to the nasal cavity, more specifically, a spray-type nasal drop agent, a nasal irrigation agent and the like can be mentioned. When applied to the skin, soaps, body soaps, shampoos, conditioners, sprays and the like can be mentioned.
　本発明の剤は、必要に応じてさらに他の成分を含んでいてもよい。他の成分としては、例えば医薬、化粧品、消毒剤、洗浄剤などに配合され得る成分である限り特に限定されるものではないが、例えば基剤、担体、溶剤、分散剤、乳化剤、緩衝剤、安定剤、賦形剤、結合剤、崩壊剤、滑沢剤、増粘剤、保湿剤、着色料、香料、キレート剤などが挙げられる。 The agent of the present invention may further contain other components, if necessary. The other components are not particularly limited as long as they are components that can be blended in, for example, pharmaceuticals, cosmetics, disinfectants, cleaning agents, etc., but for example, bases, carriers, solvents, dispersants, emulsifiers, buffers, etc. Stabilizers, excipients, binders, disintegrants, lubricants, thickeners, moisturizers, colorants, fragrances, chelating agents and the like can be mentioned.
　緩衝剤としては、特に制限されず、用途に応じて、許容される適切なものを採用することができる。好ましくはリン酸緩衝液、酢酸緩衝液等が挙げられる。 The buffering agent is not particularly limited, and an appropriate buffering agent that is acceptable can be adopted depending on the intended use. Preferred examples include a phosphate buffer solution and an acetic acid buffer solution.
　本発明の剤の有効成分の含有量は、有効成分の種類、用途、使用態様、適用対象、適用対象の状態などに左右されるものであり、限定はされないが、例えば0.000001～100重量％、好ましくは0.01～50重量％とすることができる。 The content of the active ingredient of the agent of the present invention depends on the type, use, mode of use, application target, state of application target, etc. of the active ingredient, and is not limited, but is, for example, 0.000001 to 100% by weight. It can be preferably 0.01 to 50% by weight.
　本発明の剤の適用（例えば、投与、摂取、接種など）量は、所望の効果を発現する有効量であれば特に限定されず、通常は、有効成分の重量として、一般に一日あたり0.1～1000　mg／kg体重である。上記投与量は1日1回又は2～3回に分けて投与するのが好ましく、年齢、病態、症状により適宜増減することもできる。 The amount of the agent of the present invention applied (for example, administration, ingestion, inoculation, etc.) is not particularly limited as long as it is an effective amount that exerts a desired effect, and is usually 0.1 to 0.1 per day as the weight of the active ingredient. 1000 mg / kg body weight. The above dose is preferably administered once a day or in 2 to 3 divided doses, and may be appropriately increased or decreased depending on the age, pathological condition, and symptoms.
　2-2．物品に適用する用途
　物品に適用する用途としては、例えば消毒剤、洗浄剤等が挙げられる。この場合の適用対象は、特に制限されず、各種分野において用いられている工業製品やその原材料が挙げられる。 2-2. Applications applied to articles Examples of applications applied to articles include disinfectants, detergents and the like. The application target in this case is not particularly limited, and examples thereof include industrial products and raw materials thereof used in various fields.
　物品の具体例としては、マスク、フェイスマスク、手袋等が挙げられる。また気管内挿管チューブ、バイトブロック、喉頭鏡、電極、計測機器、点滴装置、酸素マスク、鼻カテーテル、チューブ、カテーテル、白衣、ガウン、キャップ、防護服、防護シールド、手術器具等の医療器具、手術台、ベッド、ストレッチャー、車いす等が挙げられる。また、OA機器、家電、空調機器、掃除機、机、椅子、ソファー、ベンチ、窓、つり革、ハンドル、シート、自動改札機、自動券売機、自動販売機、扉、柵、手摺、食器、調理用具、包装フィルム、包装袋、瓶、ボトル、包装パック、シンク、便器、文房具、書籍、棚、歯ブラシ、鏡、空調フィルター、コート、ジャケット、ズボン、スカート、ワイシャツ、ニットシャツ、ブラウス、セーター、カーディガン、ナイトウエア、肌着、下着、オムツ、サポーター、靴下、タイツ、ストッキング、帽子、スカーフ、マフラー、襟巻き、ストール、服の裏地、服の芯地、服の中綿、作業着、ユニフォーム、学童用制服等の衣料、カーテン、アミ戸、布団地、布団綿、布団カバー、枕カバー、シーツ、マット、カーペット、タオル、ハンカチ、壁布、バンドエイド、包帯等が挙げられる。 Specific examples of articles include masks, face masks, gloves and the like. Intratracheal intubation tube, bite block, laryngoscope, electrode, measuring device, drip device, oxygen mask, nasal catheter, tube, catheter, white robe, gown, cap, protective clothing, protective shield, surgical instrument and other medical instruments, surgery Examples include operating tables, beds, stretchers, and wheelchairs. In addition, OA equipment, home appliances, air conditioning equipment, vacuum cleaners, desks, chairs, sofas, benches, windows, leather, handles, seats, automatic ticket gates, automatic ticket vending machines, vending machines, doors, fences, handrails, tableware, Cooking utensils, packaging films, packaging bags, bottles, bottles, packaging packs, sinks, toilet bowls, stationery, books, shelves, toothbrushes, mirrors, air conditioning filters, coats, jackets, trousers, skirts, shirts, knit shirts, blouses, sweaters, Cardigan, nightwear, underwear, underwear, diapers, supporters, socks, tights, stockings, hats, scarves, mufflers, scarves, stalls, clothes linings, clothes cores, clothes batting, work clothes, uniforms, for school children Examples include clothing such as uniforms, curtains, ami doors, duvets, cotton duvets, duvet covers, pillowcases, sheets, mats, carpets, towels, handkerchiefs, wall cloths, band aids, bandages and the like.
　本発明の剤を物品に適用することによって、有効成分が接触する部位において抗ウイルス作用を発揮することができる。なお、有効成分が接触する部位は、物品上の部位に限られず、物品が生体等に適用された場合には生体中の部位も包含される。 By applying the agent of the present invention to an article, it is possible to exert an antiviral effect at a site where the active ingredient comes into contact. The site where the active ingredient comes into contact is not limited to the site on the article, but also includes the site in the living body when the article is applied to a living body or the like.
　本発明の剤の剤形は特に制限されず、その用途に応じて適宜選択することができる。剤形としては、例えば液剤、乳剤、懸濁剤、分散剤、スプレー剤、エアゾール剤等の液剤；　水和剤、粉剤、粒剤、微粒剤、フロアブル剤等の固形又は半固形剤等が挙げられる。種々の物品に塗布またはコーティングすることができる。 The dosage form of the agent of the present invention is not particularly limited and can be appropriately selected according to its intended use. Examples of the dosage form include liquids such as liquids, emulsions, suspensions, dispersants, sprays and aerosols; solid or semi-solids such as wettable powders, powders, granules, fine granules and flowables. Be done. It can be applied or coated on various articles.
　本発明の剤は、必要に応じてさらに他の成分を含んでいてもよい。他の成分としては、例えば物品の洗浄剤、消毒剤などに配合され得る成分である限り特に限定されるものではないが、例えば基剤、担体、溶剤、分散剤、乳化剤、緩衝剤、安定剤、賦形剤、結合剤、崩壊剤、滑沢剤、増粘剤、保湿剤、着色料、香料、キレート剤などが挙げられる。 The agent of the present invention may further contain other components, if necessary. The other components are not particularly limited as long as they are components that can be blended in, for example, cleaning agents and disinfectants for articles, but are not particularly limited, and are, for example, bases, carriers, solvents, dispersants, emulsifiers, buffers, and stabilizers. , Excipients, binders, disintegrants, lubricants, thickeners, moisturizers, colorants, fragrances, chelating agents and the like.
　緩衝剤としては、特に制限されず、用途に応じて、許容される適切なものを採用することができる。好ましくはリン酸緩衝液、酢酸緩衝液等が挙げられる。 The buffering agent is not particularly limited, and an appropriate buffering agent that is acceptable can be adopted depending on the intended use. Preferred examples include a phosphate buffer solution and an acetic acid buffer solution.
　本発明の剤の有効成分の含有量は、有効成分の種類、用途、使用態様、適用対象、適用対象の状態などに左右されるものであり、限定はされないが、例えば0.000001～100重量％、好ましくは0.001～50重量％とすることができる。 The content of the active ingredient of the agent of the present invention depends on the type, use, mode of use, application target, state of application target, etc. of the active ingredient, and is not limited, but is, for example, 0.000001 to 100% by weight. It can be preferably 0.001 to 50% by weight.
　以下に、実施例に基づいて本発明を詳細に説明するが、本発明はこれらの実施例によって限定されるものではない。 Hereinafter, the present invention will be described in detail based on examples, but the present invention is not limited to these examples.
　試験例1．抗ウイルス作用の評価試験1
　＜サンプル液の調製＞
　Theasinensin Aサンプル液
　Theasinensin Aをろ過滅菌水で100 mMになるよう溶解した。78℃の恒温槽で数分間処理した。100 mMのサンプル液をさらに、ろ過滅菌水で2 mMに調整後、 0.45 μm cellulose acetateでフィルトレーションした後、滅菌水で400、80 μMの濃度のものを作製した。 Test example 1. Evaluation test of antiviral effect 1
<Preparation of sample solution>
Theasinensin A sample solution Theasinensin A was dissolved in sterile filtered water to 100 mM. The treatment was carried out in a constant temperature bath at 78 ° C. for several minutes. A 100 mM sample solution was further adjusted to 2 mM with filtered sterile water, filtered with 0.45 μm cellulose acetate, and then prepared with sterile water at concentrations of 400 and 80 μM.
　EGCGサンプル液1
　EGCG (-)-Epigallocatechin GallateをDMSOで100 mMになるよう溶解した。100 mMのサンプル液をさらに、ろ過滅菌水で2 mMに調整後、 0.45 μm cellulose acetateでフィルトレーションした後、滅菌水で400、80 μMの濃度のものを作製した。 EGCG sample solution 1
EGCG (-)-Epigallocatechin Gallate was lysed in DMSO to 100 mM. A 100 mM sample solution was further adjusted to 2 mM with filtered sterile water, filtered with 0.45 μm cellulose acetate, and then prepared with sterile water at concentrations of 400 and 80 μM.
　EGCGサンプル液2
　EGCG (-)-Epigallocatechin Gallateをろ過滅菌水で100 mMになるよう溶解した。78℃の恒温槽で数分間処理した。100 mMのサンプル液をさらに、ろ過滅菌水で2 mMに調整後、 0.45 μm cellulose acetateでフィルトレーションした後、滅菌水で400、80 μMの濃度のものを作製した。 EGCG sample liquid 2
EGCG (-)-Epigallocatechin Gallate was dissolved in sterile filtered water to 100 mM. The treatment was carried out in a constant temperature bath at 78 ° C. for several minutes. A 100 mM sample solution was further adjusted to 2 mM with filtered sterile water, filtered with 0.45 μm cellulose acetate, and then prepared with sterile water at concentrations of 400 and 80 μM.
　Theaflavin di-gallateサンプル液
　Theaflavin 3,3’-di-O -gallateをろ過滅菌水で100 mMになるよう溶解した。78℃の恒温槽で数分間処理した。100 mMのサンプル液をさらに、ろ過滅菌水で2 mMに調整後、 0.45 μm cellulose acetateでフィルトレーションした後、滅菌水で400、80 μMの濃度のものを作製した。 Theaflavin di-gallate sample solution Theaflavin 3,3'-di-O -gallate was dissolved in sterile filtered water to 100 mM. The treatment was carried out in a constant temperature bath at 78 ° C. for several minutes. A 100 mM sample solution was further adjusted to 2 mM with filtered sterile water, filtered with 0.45 μm cellulose acetate, and then prepared with sterile water at concentrations of 400 and 80 μM.
　＜試験プロトコール＞
　各濃度（2000, 400, 80 μM)のサンプル液あるいは滅菌水20μlに、serum-free (SF) 2 X DMEMを20μlずつ添加して浸透圧調整後、直ちにウイルス液（1.5 X 10^6 TCID50/50 μl）を各40μlずつ同時に添加した（サンプルの濃度はそれぞれ500, 100, 20, 0 μM）。1分後、速やかにSF DMEMで10段階希釈した。96-well plate に培養したVeroE6 /TMPRSS2細胞から上清を除き、各希釈液を50 μl添加した。1時間吸着後、ウイルス液を除き0.5％ FBS DMEMを100μl/wellで添加して、37℃、5％CO2/95％空気で3日間培養した。グルタルアルデヒドを100 μL/well添加して30分間固定したのち、細胞をcrystal violetで染色し、CPE（cytopathic effect）を観察し、TCID50/50μLをReed-Muench法で算出した。 <Test protocol>
Add 20 μl of serum-free (SF) 2 X DMEM to 20 μl of sample solution or sterile water at each concentration (2000, 400, 80 μM), adjust the osmotic pressure, and immediately perform virus solution (1.5 X 10 ^ 6 TCID 50 ). / 50 μl) were added simultaneously, 40 μl each (sample concentrations were 500, 100, 20, 0 μM, respectively). After 1 minute, it was immediately diluted in 10 steps with SF DMEM. The supernatant was removed from VeroE6 / TMPRSS2 cells cultured on a 96-well plate, and 50 μl of each diluted solution was added. After adsorption for 1 hour, 0.5% FBS DMEM was added at 100 μl / well, excluding the virus solution, and the cells were cultured in 37 ° C. and 5% CO 2 /95% air for 3 days. After adding 100 μL / well of glutaraldehyde and fixing for 30 minutes, the cells were stained with crystal violet, CPE (cytopathic effect) was observed, and TCID 50/50 μL was calculated by the Reed-Muench method.
　＜結果＞
　結果を図１に示す。EGCG, Theasinensin AとTheaflavin 3, 3’di-gallateをウイルスに添加すると、感染力価が著しく低下することが分かった。 EGCG, Theasinensin AとTheaflavin 3, 3’di-gallateは、いずれも濃度依存的にSARS-CoV-2を不活化することが示された。 <Result>
The results are shown in FIG. Addition of EGCG, Theasinensin A and Theaflavin 3, 3'di-gallate to the virus was found to significantly reduce the infectious titer. EGCG, Theasinensin A and Theaflavin 3, 3'di-gallate were all shown to inactivate SARS-CoV-2 in a concentration-dependent manner.
　試験例2．抗ウイルス作用の評価試験2
　＜サンプル液の調製＞
　Theasinensin Aをろ過滅菌水で100 mMになるよう溶解した。78℃の恒温槽で数分間処理した。100 mMの溶液をさらに、ろ過滅菌水で1 mMに調整後、 0.45 μm cellulose acetateでフィルトレーションして、サンプル液を得た。 Test example 2. Evaluation test of antiviral effect 2
<Preparation of sample solution>
Theasinensin A was dissolved in sterile filtered water to 100 mM. The treatment was carried out in a constant temperature bath at 78 ° C. for several minutes. A 100 mM solution was further adjusted to 1 mM with filtered sterile water, and then filtered with 0.45 μm cellulose acetate to obtain a sample solution.
　＜Post protocol＞
　サンプル液に1.0％ FBS ２XDMEMを等量添加して浸透圧を調整した後0.5％ FBS DMEM （MS)で2段階希釈し、直ちに使用した。96-well plate にVeroE6 /TMPRSS2細胞を5 X 10^4/100μl/wellで播き15時間培養した後、細胞から上清を除きSARS-CoV-2 をMOI 5で添加し、1h 吸着させた。ウイルス液を除き各濃度のSample液あるいはMSを100μl/wellで添加し、30時間培養した。細胞のviabilityを下記の方法で定量した。 <Post protocol>
After adjusting the osmotic pressure by adding an equal amount of 1.0% FBS 2XDMEM to the sample solution, it was diluted in two steps with 0.5% FBS DMEM (MS) and used immediately. VeroE6 / TMPRSS2 cells were seeded on a 96-well plate at 5 X 10 ^ 4/100 μl / well and cultured for 15 hours. After removing the supernatant from the cells, SARS-CoV-2 was added with MOI 5 and adsorbed for 1 h. The sample solution or MS of each concentration excluding the virus solution was added at 100 μl / well, and the cells were cultured for 30 hours. The viability of the cells was quantified by the following method.
　＜Mix protocol＞
　サンプル液にserum-free (SF) 2X DMEMを等量添加して浸透圧を調整した後SF DMEM（MS)で2段階希釈し、直ちに使用した。各濃度のSample液、あるいはSF DMEM（MS）100μlに、SARS-CoV-2 （1.5 X 10^6/50 μl）を10μl添加し、数分間室温に静置した。前日にVeroE6 /TMPRSS2細胞を5 X 10^4/100μl/wellで播き15時間培養した96-well plateから上清を除き、上記のウイルス/サンプル液を50 μ l添加した(MOI 3)。1h 吸着後ウイルス液を除きMSを100μl/wellで添加し、30時間培養した。細胞のviabilityを下記の方法で定量した。 <Mix protocol>
After adjusting the osmotic pressure by adding an equal amount of serum-free (SF) 2X DMEM to the sample solution, it was diluted in two steps with SF DMEM (MS) and used immediately. 10 μl of SARS-CoV-2 (1.5 X 10 ^ 6/50 μl) was added to 100 μl of Sample solution of each concentration or SF DMEM (MS), and the mixture was allowed to stand at room temperature for several minutes. The supernatant was removed from a 96-well plate in which Vero E6 / TMPRSS2 cells were sown at 5 X 10 ^ 4/100 μl / well and cultured for 15 hours the day before, and 50 μl of the above virus / sample solution was added (MOI 3). After adsorption for 1h, the virus solution was removed, MS was added at 100 μl / well, and the cells were cultured for 30 hours. The viability of the cells was quantified by the following method.
　＜細胞のViabilityの定量方法＞
Plateから培地を除去し、PBSで洗浄した。フェノールレッドフリー培地にCell Count Reagent SF （ナカライ）を20%混合し、細胞に50 μl/well添加して50分培養した。ブランクとして、細胞を培養していないウェルに試薬混合液のみを添加したウェルも準備した。反応終了後、10% SDSを20 μl/well加え、ウェルに残存しているウイルスを不活化した。プレートリーダーにて波長450 nmの吸光度を測定した。測定はテトラプリケートで行った。 <Method for quantifying cell Viability>
Medium was removed from the Plate and washed with PBS. 20% of Cell Count Reagent SF (Nacalai) was mixed with phenol red-free medium, 50 μl / well was added to the cells, and the cells were cultured for 50 minutes. As a blank, a well in which only the reagent mixture was added to the well in which the cells were not cultured was also prepared. After completion of the reaction, 20 μl / well of 10% SDS was added to inactivate the virus remaining in the well. The absorbance at a wavelength of 450 nm was measured with a plate reader. The measurement was performed with tetraplicate.
　＜結果＞
　結果を図２～３に示す。 <Result>
The results are shown in FIGS.
　図２は＜Post protocol＞の結果である。TheasinensinAを添加しなかった細胞に比べて、TheasinensinAを感染後に添加した細胞は、ウイルス感染によるviabilityの低下が抑制されている。感染後に細胞をTheasinensinAで処理することにより、ウイルス感染を減弱させることができた。 Figure 2 shows the result of <Post protocol>. Compared with the cells to which Theasinensin A was not added, the cells to which Theasinensin A was added after the infection suppressed the decrease in viability due to the virus infection. Treatment of cells with Theasinensin A after infection could attenuate viral infection.
　図３は＜Mix protocol＞の結果である。TheasinensinAを添加しなかったウイルスに比べて、感染前と細胞への吸着のときにTheasinensinAを添加したウイルスは、感染後に細胞のviabilityを低下させない。SARS-CoV-2をTheasinensinAで処理することにより、感染力を低下させることができた。 Figure 3 shows the result of <Mix protocol>. Compared to viruses without Theasinensin A, viruses with Theasinensin A added before infection and during adsorption to cells do not reduce the viability of cells after infection. Treatment of SARS-CoV-2 with Theasinensin A was able to reduce infectivity.
　試験例3．抗ウイルス作用の評価試験3
　本試験の方法の概略を図４に示す。VeroE6/TMPRSS2細胞を24-well plate に2.5x10^5/500μl/wellで播き24時間培養した。細胞から上清を除き、SARS-CoV-2 を1.25x106TCID50/100μLで添加して37 Cで1h 吸着させたのち、ウイルス液を除いた。水またはDMSOに溶解したEGCGを、0.5％ FBS DMEM（MS)で希釈し、250μMまたは25μMまたは0μMになるように500μl/wellで添加し、16時間培養した。Wellから上清を除き、 MSで洗い、MSを添加して8時間培養した。上清を回収し、TCID50アッセイに供した。また上清からRNAを抽出し、qRT-PCRにてN geneのRNAを定量した。 Test example 3. Evaluation test of antiviral effect 3
The outline of the method of this test is shown in FIG. VeroE6 / TMPRSS2 cells were seeded on a 24-well plate at 2.5x10 ^ 5/500 μl / well and cultured for 24 hours. The supernatant was removed from the cells, SARS-CoV-2 was added at 1.25x10 6 TCID 50/100 μL, and the cells were adsorbed at 37 C for 1 h, and then the virus solution was removed. EGCG dissolved in water or DMSO was diluted with 0.5% FBS DMEM (MS), added at 500 μl / well to 250 μM or 25 μM or 0 μM, and cultured for 16 hours. The supernatant was removed from Well, washed with MS, MS was added, and the cells were cultured for 8 hours. The supernatant was collected and subjected to the TCID 50 assay. RNA was also extracted from the supernatant, and RNA of N gene was quantified by qRT-PCR.
　＜TCID50アッセイ＞
　Day -1
　VeroE6/TMPRSS2細胞を5.0 x 104 cells/100μLで96穴プレートに播種した。培地は0.5%ウシ胎仔血清添加DMEM培地である。37℃、5% CO2/95% 空気下で、24時間培養した。 <TCID 50 Assay>
Day -1
Vero E6 / TMPRSS2 cells were seeded on a 96-well plate at 5.0 x 10 4 cells / 100 μL. The medium is DMEM medium supplemented with 0.5% fetal bovine serum. Incubated for 24 hours at 37 ° C., 5% CO 2 / 95% air.
　Day 0
　各サンプル500μLにSARS-CoV-2（5 X 105 TCID50/50μL）20μLを添加してインキュベートした。添加してから1分間経過後、直ちに、希釈液として0.5％FBS DMEMを使用して10倍希釈系列を調製した。前日（Day -1）に細胞を播種し培養を開始した96穴プレートから培養上清を棄て、各希釈液を50μL添加した（quadruplicate）。50分間吸着させ（10分毎にtilting）た後、0.5％FBS DMEMを50μL添加した。37℃、5% CO2/95% 空気下で、72時間培養した。 Day 0
20 μL of SARS-CoV-2 (5 X 10 5 TCID 50/50 μL) was added to 500 μL of each sample and incubated. Immediately after 1 minute of addition, a 10-fold dilution series was prepared using 0.5% FBS DMEM as the diluent. The culture supernatant was discarded from the 96-well plate in which the cells were seeded and cultured on the previous day (Day -1), and 50 μL of each diluted solution was added (quadruplicate). After adsorbing for 50 minutes (tilting every 10 minutes), 50 μL of 0.5% FBS DMEM was added. Incubated for 72 hours at 37 ° C. and 5% CO 2 / 95% air.
　Day 3
細胞（96穴プレート）にグルタルアルデヒド溶液（25％W/V）を100 μL添加して、室温で30分間静置した。培養液・グルタルアルデヒド混合液を捨てて、ウェルを水道水で洗浄した。室温で静置して乾燥させた。固定した細胞（96穴プレート）に1％クリスタルバイオレット染色液を100μL添加して、室温で30分間静置した。染色液を捨てて、ウェルを水道水で洗浄した。室温で静置して乾燥させた後、プレートを写真撮影して、染色の有無、CPEを観察した。TCID50/50μLをReed-Muench法で算出し、得られた値に基づいてウイルス減少率を算出した。 Day 3
100 μL of glutaraldehyde solution (25% W / V) was added to the cells (96-well plate), and the cells were allowed to stand at room temperature for 30 minutes. The culture solution and glutaraldehyde mixture were discarded, and the wells were washed with tap water. It was allowed to stand at room temperature and dried. 100 μL of 1% crystal violet stain was added to the fixed cells (96-well plate), and the cells were allowed to stand at room temperature for 30 minutes. The stain was discarded and the wells were washed with tap water. After allowing to stand at room temperature and drying, the plate was photographed to observe the presence or absence of staining and CPE. TCID 50/50 μL was calculated by the Reed-Muench method, and the virus reduction rate was calculated based on the obtained values.
　＜RNA抽出とqRT-PCR＞
　TRI Reagent(R) LS、またはSepasol RNA I Super Gにて、培養上清からRNAを抽出した。回収したRNA(8μL)は、ReverTra Ace(R) qPCR RT Master Mix（TOYOBO）にて逆転写した。温度条件は、37℃(30min),50℃(5min)で行った。qPCRは、以下を混ぜて行った。5μL        GoTaq(R) Probe qPCR MasterMix (Promega)0.22μL     40μM Primer (F)   Final: 880nM0.22μL     40μM Primer (R)   Final: 880nM0.06μL     40μM Probe       Final: 240nM2μL        cDNA
2.5μL      D2W
10μL       Total。 <RNA extraction and qRT-PCR>
RNA was extracted from the culture supernatant with TRI Reagent (R) LS or Sepasol RNA I Super G. The recovered RNA (8 μL) was reverse transcribed with ReverTra Ace (R) qPCR RT Master Mix (TOYOBO). The temperature conditions were 37 ° C (30 min) and 50 ° C (5 min). qPCR was performed by mixing the following. 5 μL GoTaq (R) Probe qPCR MasterMix (Promega) 0.22 μL 40 μM Primer (F) Final: 880nM 0.22 μL 40 μM Primer (R) Final: 880nM 0.06 μL 40 μM Probe Final: 240nM 2 μL cDNA
2.5 μL D2W
10 μL Total.
　プライマーとプローブの配列は以下のとおりである。
Primer (F)： 5’- AAATTTTGGGGACCAGGAAC -3’（配列番号1）;Primer (R)： 5’ - TGGCAGCTGTGTAGGTCAAC-3’’（配列番号2）;Probe： 5’- (FAM) ATGTCGCGCATTGGCATGGA（配列番号3） (BHQ) -3’)。 The sequence of primers and probes is as follows.
Primer (F): 5'-AAATTTTGGGGACCAGGAAC -3'(SEQ ID NO: 1); Primer (R): 5'--TGGCAGCGTGTGTAGGTCAAC-3'' (SEQ ID NO: 2); Probe: 5'-(FAM) ATGTCGCGCATTGGCATGGA (SEQ ID NO: 3) ) (BHQ) -3').
　温度条件は以下のとおりである。
95℃ 20秒
95℃ 01秒
60℃ 20秒     
サイクル数：50cycles 
StepOnePlus（ABI）（器械）を用いStepOne Software（ ABI ）（ソフト）で解析した。 The temperature conditions are as follows.
95 ℃ 20 seconds
95 ℃ 01 seconds
60 ℃ 20 seconds
Number of cycles: 50 cycles
Analysis was performed with StepOne Software (ABI) (software) using StepOnePlus (ABI) (instrument).
　＜結果＞
　結果を図５及び図６に示す。感染後の細胞にEGCGを添加し、培養後に上清を回収して、ウイルス力価の測定とウイルスRNAの定量を行ったところ、どちらも濃度依存的に減少したことが分かった。EGCGが感染後の細胞に作用して、ウイルス感染を抑制したことが示された。 <Result>
The results are shown in FIGS. 5 and 6. When EGCG was added to the infected cells and the supernatant was collected after culturing, the virus titer was measured and the virus RNA was quantified, and it was found that both decreased in a concentration-dependent manner. It was shown that EGCG acted on post-infection cells to suppress viral infection.

Claims (18)

  1. 茶成分を含有する、抗ウイルス剤。 An antiviral agent containing a tea component.
  2. 前記茶成分がポリフェノール類である、請求項１に記載の抗ウイルス剤。 The antiviral agent according to claim 1, wherein the tea component is polyphenols.
  3. 前記ポリフェノール類がカテキン類又はカテキン酸化重合物類である、請求項２に記載の抗ウイルス剤。 The antiviral agent according to claim 2, wherein the polyphenols are catechins or catechin oxidation polymers.
  4. 前記カテキン類がガレート型カテキン類である、請求項３に記載の抗ウイルス剤。 The antiviral agent according to claim 3, wherein the catechins are gallate-type catechins.
  5. 前記カテキン酸化重合物類がテアシネンシン類又はテアフラビン類である、請求項３に記載の抗ウイルス剤。 The antiviral agent according to claim 3, wherein the catechin oxidation polymers are theacinencins or theaflavins.
  6. ウイルス感染抑制、ウイルスの細胞感染力価低下、ウイルスによる細胞死の抑制、及びウイルス不活化からなる群より選択される少なくとも１種に用いるための、請求項１～５のいずれかに記載の抗ウイルス剤。 The anti-antifecty according to any one of claims 1 to 5 for use in at least one selected from the group consisting of virus infection suppression, virus cell infection titer reduction, virus-induced cell death suppression, and virus inactivation. Viral agent.
  7. 前記ウイルスがコロナウイルスである、請求項１～６のいずれかに記載の抗ウイルス剤。 The antiviral agent according to any one of claims 1 to 6, wherein the virus is a coronavirus.
  8. 前記ウイルスがSARS-CoV-2である、請求項１～７のいずれかに記載の抗ウイルス剤。 The antiviral agent according to any one of claims 1 to 7, wherein the virus is SARS-CoV-2.
  9. 生体に適用するために用いられる、請求項１～８のいずれかに記載の抗ウイルス剤。 The antiviral agent according to any one of claims 1 to 8, which is used for application to a living body.
  10. 医薬、化粧品、飲料組成物、食品組成物、食品添加剤、消毒剤又は洗浄剤である、請求項９に記載の抗ウイルス剤。 The antiviral agent according to claim 9, which is a pharmaceutical, cosmetics, beverage composition, food composition, food additive, disinfectant or detergent.
  11. COVID-19の予防又は治療剤である、請求項９又は１０に記載の抗ウイルス剤。 The antiviral agent according to claim 9 or 10, which is a prophylactic or therapeutic agent for COVID-19.
  12. 物品に適用するために用いられる、請求項１～８のいずれかに記載の抗ウイルス剤。 The antiviral agent according to any one of claims 1 to 8, which is used for application to an article.
  13. 消毒剤又は洗浄剤である、請求項１２に記載の抗ウイルス剤。 The antiviral agent according to claim 12, which is a disinfectant or a cleaning agent.
  14. 茶成分を生体又は物品に適用することを含む、抗ウイルス方法。 An antiviral method comprising applying a tea ingredient to a living body or an article.
  15. ウイルス感染症を有する対象に茶成分を摂取させることを含む、抗ウイルス方法。 An antiviral method comprising feeding a subject with a viral infection a tea component.
  16. 抗ウイルス剤としての使用のための、茶成分。 A tea ingredient for use as an antiviral agent.
  17. 茶成分の、抗ウイルス剤の製造のための使用。 Use of tea ingredients for the production of antiviral agents.
  18. 茶成分の、抗ウイルス剤としての使用。 Use of tea ingredients as an antiviral agent.
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WO2023026867A1 (en) * 2021-08-24 2023-03-02 株式会社Hpg Aqueous catechin-containing solution composition having excellent storage stability, and use thereof

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2023026867A1 (en) * 2021-08-24 2023-03-02 株式会社Hpg Aqueous catechin-containing solution composition having excellent storage stability, and use thereof

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