Composition for SARS-CoV-2 virus infection inhibition

Abstract

To provide an inventive SARS-CoV-2 virus infection inhibitor that is simple to use only through oral intake or routine oral care activities and excellent in infection control effect, so as to meet demands of effective agents for infection inhibitor against SARS-CoV-2 virus and methods that allow easy infection control through everyday activities.SOLUTION: There is provided an SARS-CoV-2 virus infection inhibitor, which is rooibos extract, is utilized as an active ingredient.SELECTED DRAWING: None

Description

Technical Field

[0001] The present invention relates to a composition for suppressing SARS-CoV-2 virus infection.

Background Art

[0002] The SARS-CoV-2 virus (severe acute respiratory syndrome coronavirus 2) is the virus that causes coronavirus disease 2019 (COVID-19). As treatments for COVID-19 patients, the administration of various therapeutic agents and plasma therapy have been attempted. In addition, the development of vaccines is underway as a countermeasure for preventing SARS-CoV-2 virus infection.

[0003] As countermeasures for preventing COVID-19 infection in daily life, gargling, handwashing, and wearing masks are being strongly encouraged. There is a need for infection prevention measures that are simple to perform in daily activities, such as gargling and handwashing, and have a high effect. For example, Patent Document 1 proposes a preventive and therapeutic agent for animal coronavirus infection containing specific crude drugs such as clove, schizonepeta, mugwort, and perilla leaf as active ingredients. According to the invention of Patent Document 1, the prevention and treatment of coronavirus infection are achieved by subjecting specific crude drugs to oral ingestion.

Prior Art Documents

Patent Documents

[0004]

Patent Document 1

Summary of the Invention

Problems to be Solved by the Invention

[0005] However, no effective infection inhibitor has yet been provided against the SARS-CoV-2 virus. In addition, there is a need for a method that can be easily performed in daily activities for infection suppression. Therefore, the present invention aims to provide a SARS-CoV-2 virus infection inhibitor that exhibits excellent infection-suppressing effects simply by oral ingestion or daily oral care activities. [Means for solving the problem]

[0006] One aspect of the present invention is "a composition for inhibiting SARS-CoV-2 virus infection, containing rooibos extract as an active ingredient." The present invention has the following aspects. <1> A SARS-CoV-2 virus infection inhibitor, comprising at least one selected from the group consisting of Phellodendron amurense extract, cetylpyridinium chloride, glycyrrhetinic acid, maqui berry extract, evening primrose extract, walnut polyphenol, wasabi sulfinyl, Indian date extract, Gymnema extract, sweet tea extract, rose bud extract, curcumin, olive leaf extract, grape seed extract, rooibos extract, N-acetylglucosamine, and panaxatriol.

[0007] <2> <1> A composition for inhibiting SARS-CoV-2 virus infection, comprising the SARS-CoV-2 virus infection inhibitor described in [reference] as an active ingredient. <3> Pharmaceuticals, quasi-drugs, food products, or oral care products, <2> A composition for suppressing SARS-CoV-2 virus infection as described above.

[0008] <4> An inactivator of the SARS-CoV-2 virus, comprising at least one selected from the group consisting of Phellodendron amurense extract, cetylpyridinium chloride, glycyrrhetinic acid, maqui berry extract, evening primrose extract, walnut polyphenol, wasabi sulfinyl, Indian date extract, Gymnema extract, sweet tea extract, rose bud extract, curcumin, olive leaf extract, grape seed extract, rooibos extract, N-acetylglucosamine, and panaxatriol. <5> A SARS-CoV-2 virus removal agent comprising at least one selected from the group consisting of Phellodendron amurense extract, cetylpyridinium chloride, glycyrrhetinic acid, maqui berry extract, evening primrose extract, walnut polyphenol, wasabi sulfinyl, Indian date extract, Gymnema extract, sweet tea extract, rose bud extract, curcumin, olive leaf extract, grape seed extract, rooibos extract, N-acetylglucosamine, and panaxatriol. <6> A treatment for COVID-19 comprising at least one selected from the group consisting of Phellodendron amurense extract, cetylpyridinium chloride, glycyrrhetinic acid, maqui berry extract, evening primrose extract, walnut polyphenols, wasabi sulfinyl, Indian date extract, Gymnema extract, sweet tea extract, rose bud extract, curcumin, olive leaf extract, grape seed extract, rooibos extract, N-acetylglucosamine, and panaxatriol.

[0009] <7> Use as a SARS-CoV-2 virus infection inhibitor selected from the group consisting of Phellodendron amurense extract, cetylpyridinium chloride, glycyrrhetinic acid, maqui berry extract, evening primrose extract, walnut polyphenols, wasabi sulfinyl, Indian date extract, Gymnema extract, sweet tea extract, rose bud extract, curcumin, olive leaf extract, grape seed extract, rooibos extract, N-acetylglucosamine, and panaxatriol. <8> A method for suppressing SARS-CoV-2 virus infection, comprising ingesting or administering at least one SARS-CoV-2 virus infection suppressant selected from the group consisting of Phellodendron amurense extract, cetylpyridinium chloride, glycyrrhetinic acid, maqui berry extract, evening primrose extract, walnut polyphenol, wasabi sulfinyl, Indian date extract, Gymnema extract, sweet tea extract, rose bud extract, curcumin, olive leaf extract, grape seed extract, rooibos extract, N-acetylglucosamine, and panaxatriol. <9> It is taken or administered orally. <8> The method for suppressing SARS-CoV-2 virus infection described in [the relevant document]. <10> A method for suppressing SARS-CoV-2 virus infection, comprising performing a procedure in the oral cavity using an oral care product containing at least one SARS-CoV-2 virus infection suppressant selected from the group consisting of Phellodendron amurense extract, cetylpyridinium chloride, glycyrrhetinic acid, maqui berry extract, evening primrose extract, walnut polyphenol, wasabi sulfinyl, Indian date extract, Gymnema extract, sweet tea extract, rose bud extract, curcumin, olive leaf extract, grape seed extract, rooibos extract, N-acetylglucosamine, and panaxatriol. [Effects of the Invention]

[0010] The SARS-CoV-2 virus infection inhibitor of the present invention is highly convenient as it only requires oral ingestion or routine oral care. [Modes for carrying out the invention]

[0011] (SARS-CoV-2 virus infection suppressant) The SARS-CoV-2 virus infection inhibitor of the present invention (hereinafter sometimes simply referred to as "infection inhibitor") is at least one selected from the group consisting of Phellodendron amurense extract, cetylpyridinium chloride, glycyrrhetinic acid, Maqui berry extract, Evening primrose extract, Walnut polyphenol, Wasabi sulfinyl, Indian date extract, Gymnema extract, Sweet tea extract, Rose bud extract, Curcumin, Olive leaf extract, Grape seed extract, Rooibos extract, N-acetylglucosamine, and Panaxatriol.

[0012] In the present invention, "infection suppressant" is a concept that includes therapeutic agents for preventing infection, alleviating the symptoms of COVID-19, preventing severe cases of COVID-19, promoting early recovery from COVID-19, inactivating SARS-CoV-2 virus, and removing SARS-CoV-2 virus.

[0013] Phellodendron bark extract is a component extracted from Phellodendron amurense Rupr. The main components of Phellodendron bark extract are berberine, limonin, etc. As the extraction method of Phellodendron bark extract, a conventionally known method is used. For example, there is a method of extracting with water, a hydrophilic solvent, a hydrophobic solvent or a mixed solvent thereof, and purifying as necessary. Examples of the hydrophilic solvent include monohydric alcohols having 1 to 6 carbon atoms, polyhydric alcohols having 2 to 6 carbon atoms, etc. (the same applies hereinafter). Examples of commercially available products of Phellodendron bark extract include Phellodendron bark extract S (trade name, manufactured by Kojima Pharmaceutical Co., Ltd.). When using Phellodendron bark extract as an infection inhibitor, its dosage or intake (hereinafter sometimes collectively referred to as "dosage / intake") is preferably 0.1 to 10 g / day, more preferably 0.5 to 5 g / day, and even more preferably 1.5 to 2 g / day.

[0014] Cetylpyridinium chloride (CPC) is a kind of quaternary ammonium salt. Examples of commercially available products of cetylpyridinium chloride include cetylpyridinium chloride (manufactured by Fujifilm Wako Pure Chemical Corporation). When using cetylpyridinium chloride as an infection inhibitor, its dosage / intake is preferably 0.1 to 100 mg / day, more preferably 1 to 20 mg / day, and even more preferably 3 to 10 mg / day.

[0015] Glycyrrhetinic acid is a kind of pentacyclic terpenoid derivative. Examples of products of glycyrrhetinic acid include β-glycyrrhetinic acid (manufactured by Maruzen Pharmaceutical Co., Ltd.). When using glycyrrhetinic acid as an infection inhibitor, its dosage / intake is preferably 0.001 to 300 mg / day, more preferably 0.01 to 10 mg / day, and even more preferably 0.1 to 1 mg / day.

[0016] Maqui berry extract is an extract derived from the maqui berry. The maqui berry is an evergreen shrub belonging to the Elaeocarpaceae family, native to the Patagonia region of Argentina and Chile. Maqui berry extract contains many anthocyanins, which are antioxidants. Among the anthocyanins, maqui berry extract contains more delphinidins, which have particularly strong antioxidant activity, than blackcurrants or bilberries (a type of blueberry). Conventional methods for extracting maqui berry extract are used, such as extraction with water, a hydrophilic solvent, a hydrophobic solvent, or a mixture thereof, and purification as necessary. When using maqui berry extract as an infection inhibitor, water extraction is preferred. Examples of maqui berry extract products include Maqui Berry Extract-P35 (MaquiBright) (product name, total anthocyanin content: 35% by mass or more, total finidine content: 25% or more, manufactured by Oryza Oil & Fat Chemical Co., Ltd.). When using maqui berry extract as an infection suppressant, the dosage is preferably 1 to 10,000 mg / day, more preferably 10 to 1,000 mg / day, and even more preferably 20 to 500 mg / day.

[0017] Evening primrose extract is an extract obtained from the evening primrose plant. Polyphenols contained in evening primrose extract include gallic acid, ellagic acid, pentagalloyl glucose, catechin, and proanthocyanidin. Conventional methods for extracting evening primrose extract are used, such as extraction with water, a hydrophilic solvent, a hydrophobic solvent, or a mixture thereof, followed by purification as necessary. Examples of evening primrose extract products include Evening Primrose Extract-P (product name, manufactured by Oryza Oil & Fat Chemical Co., Ltd.). When using evening primrose extract as an infection suppressant, the dosage is preferably 1 to 10,000 mg / day, more preferably 10 to 1,000 mg / day, and even more preferably 20 to 500 mg / day.

[0018] Walnut polyphenols are components extracted from walnut seeds. Walnut polyphenols are found only in the outer layer of the seed, and their main components are hydrolyzable polyphenols, with Pedunculagin, Ellagic acid, Tellimagrandin I, Casuarictin, Tellimagranin II, Rugosin C, and Casuarinin. Examples of walnut polyphenol products include Walnut Polyphenol-P30 (product name, manufactured by Oryza Oil & Fat Chemical Co., Ltd.). When using walnut polyphenols as an infection suppressant, the dosage is preferably 1 to 10,000 mg / day, more preferably 10 to 1,000 mg / day, and even more preferably 20 to 500 mg / day.

[0019] Wasabi sulfinyl is an extract from wasabi plants, including the rhizome of wasabi. It is found in high concentrations in the rhizome of wasabi. The main component of wasabi sulfinyl is 6-methylsulfinylhexyl isothiocyanate (6-MSITC), which is a type of mustard oil. Examples of products containing wasabi sulfinyl include Wasabi Sulfinyl (product name, manufactured by Kin'in Co., Ltd.). When using wasabi sulfinil as an infection suppressant, the dosage is preferably 1 to 10,000 mg / day, more preferably 10 to 1,000 mg / day, and even more preferably 20 to 500 mg / day.

[0020] Indian date extract is an ingredient extracted from Indian dates (Tamarindus indica L.). Indian dates are evergreen trees native to Africa, growing wild in tropical regions of Asia and Africa, and are cultivated in India and Thailand. The main component of Indian date extract is polyphenols. Conventional methods for extracting Indian date extract are used, for example, by extracting with water, a hydrophilic solvent, a hydrophobic solvent, or a mixture thereof, and purifying as necessary. Examples of products containing Indian date extract include Indian Date Extract Powder MF (product name, manufactured by Maruzen Pharmaceutical Co., Ltd.). When using Indian date extract as an infection suppressant, the dosage is preferably 1 to 10,000 mg / day, more preferably 10 to 1,000 mg / day, and even more preferably 20 to 500 mg / day.

[0021] Gymnema extract is an ingredient extracted from Gymnema. Gymnema is an evergreen vine plant distributed in tropical regions such as southern China, Taiwan, Vietnam, and India. The main component of Gymnema extract is gymnemic acid. Conventional methods for extracting Gymnema extract are used, for example, by extracting with water, a hydrophilic solvent, a hydrophobic solvent, or a mixture thereof, and purifying as necessary. Examples of products containing Gymnema extract include Gymnema Extract Powder FG (product name, manufactured by Maruzen Pharmaceutical Co., Ltd.). When using Gymnema extract as an infection suppressant, the dosage is preferably 1 to 10,000 mg / day, more preferably 10 to 1,000 mg / day, and even more preferably 20 to 500 mg / day.

[0022] Sweet tea extract is an ingredient extracted from sweet tea. Sweet tea is a deciduous shrub belonging to the genus Rubus in the Rosaceae family, distributed from the Guangxi Zhuang Autonomous Region to Guangdong Province. The main components of sweet tea extract include phenols such as sweet tea polyphenol (GOD) and tannins. Conventional methods known as sweet tea extract are used for extraction, such as extraction with water, a hydrophilic solvent, a hydrophobic solvent, or a mixture thereof, and purification as necessary. When sweet tea extract is used as an infection inhibitor, hot water extraction is preferred. Examples of sweet tea extract products include Sweet Tea Extract M Powder (product name, GOD content: 3.5% by mass or more, polyphenol content: 15% by mass or more, manufactured by Maruzen Pharmaceutical Co., Ltd.). When using sweet tea extract as an infection suppressant, the dosage is preferably 1 to 10,000 mg / day, more preferably 10 to 1,000 mg / day, and even more preferably 20 to 500 mg / day.

[0023] Rosebud extract is an extract derived from the European rose. Examples of European roses include Damask rose, musk rose, French rose, Chinese rose, peony rose, wild rose, and luscious wild rose. The main components of rosebud extract include rose oil (citronellol, geraniol, linalool, etc.), sugars, tannins, gallic acid, and pectin. Conventional methods for extracting rosebud extract are used, such as extraction with water, hydrophilic solvents, hydrophobic solvents, or mixtures thereof, and purification as necessary. Examples of products containing rosebud extract include Rosebud Extract Powder MF (product name, manufactured by Maruzen Pharmaceutical Co., Ltd.). When using rose bud extract as an infection suppressant, the dosage is preferably 1 to 10,000 mg / day, more preferably 10 to 1,000 mg / day, and even more preferably 20 to 500 mg / day.

[0024] Curcumin is a polyphenol compound extracted from turmeric and other plants. Curcumin is a general term for curcumin, demethoxycurcumin, and bisdemethoxycurcumin, and may also be a mixture of the three components. Conventional methods known for curcumin extraction are used, for example, extraction with water, a hydrophilic solvent, a hydrophobic solvent, or a mixture thereof, and purification as necessary. When curcumin is used as an infection inhibitor, ethanol extraction is preferred as the extraction method for curcumin. Examples of curcumin products include Curcumin C3 Complex (product name, total content of curcumin, demethoxycurcumin, and bisdemethoxycurcumin: 95% by mass or more, manufactured by Sabinsa). When curcumin is used as an infection suppressant, the dosage is preferably 1 to 10,000 mg / day, more preferably 3 to 1,000 mg / day, and even more preferably 5 to 100 mg / day.

[0025] Olive leaf extract is an ingredient extracted from olive leaves. The main component of olive leaf extract is oleuropein. Conventional methods for extracting olive leaf extract are used, such as extraction with water, a hydrophilic solvent, a hydrophobic solvent, or a mixture thereof, and purification as necessary. Examples of olive leaf extract products include Olive Leaf (product name, manufactured by Sabinsa). When using olive leaf extract as an infection suppressant, the dosage is preferably 1 to 10,000 mg / day, more preferably 10 to 1,000 mg / day, and even more preferably 20 to 500 mg / day.

[0026] Grape seed extract is an ingredient extracted from grape seeds. The main components of grape seed extract are proanthocyanidins, anthocyanins, flavonols, etc. Conventional methods are used to extract grape seed extract, for example, by extracting with water, a hydrophilic solvent, a hydrophobic solvent, or a mixture thereof, and purifying as necessary. When grape seed extract is used as an infection inhibitor, ethanol extraction is preferred. Examples of commercially available grape seed extract products include Grape Seed (product name, manufactured by Sabinsa). When using grape seed extract as an infection suppressant, the dosage is preferably 1 to 10,000 mg / day, more preferably 10 to 1,000 mg / day, and even more preferably 20 to 500 mg / day.

[0027] Rooibos extract is an ingredient extracted from Aspalathus linearis. Conventional methods for extracting rooibos extract are used, for example, by extracting with water, ethanol, or a mixture thereof, but extraction with water is preferred. After extraction, the process may include a step of contacting the solvent with a porous adsorbent such as activated carbon or synthetic adsorbent. The main components contained in rooibos extract are luteolin, aspalathin, eriodictyol-6-C-glucoside, orientin, etc. Examples of commercially available rooibos extracts include Pure Rooibos Extract L (product name, manufactured by Maruzen Pharmaceutical Co., Ltd.). When using rooibos extract as an infection suppressant, the dosage is preferably 1 to 10,000 mg / day, more preferably 10 to 1,000 mg / day, and even more preferably 20 to 500 mg / day.

[0028] N-acetylglucosamine is an amino sugar synthesized from glucosamine, a type of sugar, via glucosamine-6-phosphate. When using N-acetylglucosamine as an infection suppressant, the dosage is preferably 10 to 10,000 mg / day, more preferably 50 to 5,000 mg / day, and even more preferably 100 to 3,000 mg / day.

[0029] Panaxatriol is a compound belonging to the dammarane triterpene class, and can be obtained from commercially available sources, by synthesis, or from plants, such as ginseng and Panax notoginseng. Panaxatriol may be used as an isolated infection inhibitor, or processed Panax notoginseng may be used as an infection inhibitor. A method for obtaining panaxatriol from Panax notoginseng is disclosed in Japanese Patent Publication No. 2011-263313. The invention described in the above publication involves extracting Panax notoginseng powder with a water-ethanol solution containing hydrochloric acid to obtain a hydrolyzed Panax notoginseng solution, neutralizing this with caustic soda to reduce the ethanol concentration, filtering the solution, and drying the residue to obtain panaxatriol (PT).

[0030] Panaxatriol (PT) can be obtained, for example, by the following method: 1 kg of Panax notoginseng powder (manufactured by Matsuura Pharmaceutical Co., Ltd.) is suspended in 10 L of a 25% by mass ethanol aqueous solution containing 5.9% by mass hydrochloric acid (2 mol / L hydrochloric acid), and reacted at 70°C for 6 hours with slow stirring. The reaction solution is then cooled on ice, and a 5 mol / L sodium hydroxide aqueous solution is added to adjust the pH to 7.0. The pH-adjusted solution is then diluted 10-fold with distilled water, filtered by suction, and separated into filtrate and residue. The resulting residue is freeze-dried to obtain 180 g of freeze-dried powder. An ethanol solution containing 3% by mass of the freeze-dried powder is prepared. Insoluble matter is then removed from the ethanol solution using filter paper, and the ethanol solution is concentrated 8-fold using a rotary evaporator. The concentrated ethanol solution is added to a glass column packed with silica gel (silica gel 60N, manufactured by Kanto Chemical Co., Ltd.), and column fractionation is performed using chloroform:ethanol = 10:1 (V / V) as the eluent. On a normal-phase TLC with chloroform:ethanol = 10:1 (V / V) as the developing solvent, the fraction corresponding to an Rf value of 0.4 is concentrated to obtain high-purity panaxatriol (PT).

[0031] When using panaxatriol as an infection suppressant, the dosage is preferably 1 to 100 mg / day, more preferably 2 to 50 mg / day, and even more preferably 3 to 30 mg / day. When using panaxatriol as an infection suppressant, the dosage is preferably 1 to 100 mg / day, more preferably 2 to 50 mg / day, and even more preferably 3 to 30 mg / day.

[0032] Among the above-mentioned infection inhibitors, cetylpyridinium chloride, maqui berry extract, sweet tea extract, curcumin, grape seed extract, and rooibos extract are preferred. These infection inhibitors can further enhance the inhibitory effect against the SARS-CoV-2 virus. The above-mentioned infection inhibitors may be used individually or in combination of two or more.

[0033] (Composition for suppressing SARS-CoV-2 virus infection) The SARS-CoV-2 virus infection suppression composition of the present invention (hereinafter sometimes simply referred to as the "infection suppression composition") contains the infection suppressant of the present invention as an active ingredient. "Contained as an active ingredient" means that it is contained in an amount that produces an infection suppression effect.

[0034] The infection-inhibiting composition of the present invention is not particularly limited by its route of intake or administration (hereinafter collectively referred to as "intake / administration route"), as long as it achieves the desired effect of the present invention. Examples of intake / administration routes include oral administration (e.g., oral cavity, sublingual, etc.) and parenteral administration (eye drops, intravenous, intramuscular, subcutaneous, transdermal, nasal, transpulmonary, etc.). Among these, less invasive routes are preferred, with oral administration being more preferred. Furthermore, it may be incorporated into oral care products such as toothpaste, mouthwash, and mouth spray, which are not intended for oral administration but are used for oral treatment. Examples of infection-inhibiting compositions include pharmaceuticals, quasi-drugs, foods (including functional foods and beverages), oral care products, cosmetics, air fresheners (fragrances, etc.), and cleaning agents, among which pharmaceuticals, quasi-drugs, foods, or oral care products are preferred.

[0035] The dosage form of the infection-suppressing composition is determined appropriately, taking into consideration the route of ingestion and administration, and may be in solid or liquid form. Dosage forms of infection-inhibiting compositions for oral ingestion or administration include, for example, solids such as powders, granules, capsules, sachets, tablets, boluses, and lozenges; liquids such as aqueous solutions, extracts, suspensions, syrups, elixirs, emulsions, and dispersions; and semi-liquid, creamy, and paste-like forms. Infection-inhibiting compositions may be ingested or administered in pill form (powder or concentrated liquid in a capsule) or in powder or granular form (including freeze-dried granules) that can be dispersed in a liquid such as water or hot water (similar to drinking powdered tea).

[0036] Examples of infection-suppressing compositions that are pharmaceuticals or quasi-drugs taken orally or administered orally include tablets, granules, fine granules, capsules, powders, lozenges, pills, chewables, liquids, emulsions, suspensions, jellies, mouthwashes, sprays, and the like.

[0037] There are no particular restrictions on food-based infection-inhibiting compositions, and examples include beverages (soft drinks, carbonated drinks, nutritional drinks, powdered drinks, fruit drinks, milk drinks, jelly drinks, etc.), confectionery (cookies, cakes, gum, candy, tablets, gummies, manju, yokan, pudding, jelly, ice cream, sherbet, etc.), processed seafood (kamaboko, chikuwa, hanpen, etc.), processed livestock products (hamburgers, ham, sausages, wieners, cheese, butter, yogurt, fresh cream, margarine, fermented milk, etc.), soups (powdered soups, liquid soups, etc.), staple foods (rice, noodles (dried noodles, fresh noodles), bread, cereals, etc.), and seasonings (mayonnaise, shortening, dressings, sauces, dips, soy sauce, etc.).

[0038] Examples of infection-inhibiting compositions for oral care products (hereinafter sometimes referred to as "oral compositions") include toothpaste, mouthwash, mouth spray, oral paste, ointment, and patch. Examples of toothpaste include paste toothpaste, liquid toothpaste, liquid toothpaste, and moistened toothpaste. In addition, oral compositions include tablets, gummies, candies, chewing gum, etc., which are placed in the oral cavity and used for oral treatment. Examples of tablets include lozenges, candies, and tablets. Oral compositions can be prepared and used in various forms, such as paste, gel, liquid, or solid, depending on the method of use. Among the above, toothpaste, mouthwash, tablets, gummies, and candies are preferred as oral compositions, with toothpaste and mouthwash being more preferred.

[0039] The dosage form of the parenterally administered infection-suppressing composition is not particularly limited and may be solid, liquid, semi-liquid, cream, paste, gel, etc. Examples of infection-suppressing compositions for parenteral administration include pharmaceuticals and quasi-drugs such as eye drops, ophthalmic preparations, injections, transdermal preparations, nasal preparations, and pulmonary preparations. Examples of eye drops include liquid compositions such as aqueous solutions, extracts, suspensions, emulsions, and dispersions. Examples of ophthalmic preparations include compositions such as semi-liquid, cream, and paste. Examples of injectable preparations include intravenous, intramuscular, or subcutaneous injection preparations in the form of liquids such as solutions, extracts, suspensions, emulsions, and dispersions. Examples of transdermal administration agents include liquid compositions such as aqueous solutions, extracts, suspensions, emulsions, and dispersions, as well as creams and gels (such as patches). Nasal administration preparations include liquids such as aqueous solutions, extracts, suspensions, emulsions, and dispersions, as well as powders and granules. Examples of transpulmonary administration agents include liquids such as aqueous solutions, extracts, suspensions, emulsions, and dispersions, as well as powders and granules.

[0040] <Infection inhibitors in infection control compositions> The amount of infection inhibitor contained in the infection-inhibiting composition is determined appropriately, taking into consideration the oral / ingestion route of the infection-inhibiting composition, the dosage form of the infection-inhibiting composition, the type of infection-inhibiting composition, the amount administered / ingested of the infection inhibitor, the type of infection inhibitor, etc. When an infection-inhibiting composition is an oral drug, an oral quasi-drug, an injection, or a food product, etc., which may be hereinafter referred to as an "ingestion / administration type composition", the amount of infection inhibitor in the infection-inhibiting composition is preferably, for example, 0.001 to 100% by mass, and more preferably 0.01 to 90% by mass, based on the total mass of the infection-inhibiting composition. The infection inhibitor in the infection-inhibiting composition may be a single type or a combination of two or more types.

[0041] In ingestible / administered compositions, when one or more selected from Phellodendron bark extract, cetylpyridinium chloride, and glycyrrhetinic acid are incorporated as infection inhibitors, the amount of infection inhibitors is preferably 0.01 to 90% by mass, and more preferably 1 to 80% by mass, relative to the total mass of the infection inhibitory composition.

[0042] In ingestible / administered compositions, when maqui berry extract, evening primrose extract, walnut polyphenol, wasabi sulfinyl, Indian date extract, Gymnema extract, sweet tea extract, rose bud extract, olive leaf extract, rooibos extract, and N-acetylglucosamine are incorporated as infection inhibitors, the amount of infection inhibitors incorporated is preferably 1 to 90% by mass, and more preferably 10 to 80% by mass, relative to the total mass of the infection inhibitory composition.

[0043] In ingestible / administered compositions, when panaxatriol is incorporated into the infection-inhibiting composition as an infection inhibitor, the amount of the infection inhibitor is preferably 0.5 to 80% by mass, and more preferably 1 to 50% by mass, relative to the total mass of the infection-inhibiting composition.

[0044] When the infection prevention composition is an oral composition, the amount of infection inhibitor in the oral composition can be appropriately determined considering the dosage form, type, etc. of the oral composition. The amount of infection inhibitor in the oral composition can be appropriately determined within the range of 0.0001 to 100% by mass of the total mass of the oral composition. The infection inhibitor in the oral composition may be a single type or a combination of two or more types.

[0045] In oral compositions, when infection inhibitors such as Phellodendron amurense extract, cetylpyridinium chloride, glycyrrhetinic acid, Maqui berry extract, Evening primrose extract, Walnut polyphenol, Wasabi sulfinyl, Indian date extract, Gymnema extract, Sweet tea extract, Rose bud extract, Curcumin, Olive leaf extract, Grape seed extract, Rooibos extract, N-acetylglucosamine, and Panaxatriol are included, the amount of infection inhibitor is preferably 0.0001 to 10% by mass, and more preferably 0.001 to 5% by mass, relative to the total mass of the infection inhibitory composition.

[0046] <Optional components in infection-inhibiting compositions> The ingestible / administered composition may contain optional components as needed, provided that they do not impair the effects of the present invention. Examples of optional components include various additives. The content of optional components can be appropriately set according to the purpose, as long as it does not interfere with the effects of the present invention.

[0047] Additives include various sweeteners (sucrose, fructose-glucose liquid sugar, honey, erythritol, maltitol, fructose, reduced palatinose, xylitol, aspartame, acesulfame potassium, sucralose, etc.), stabilizers (sodium edetate, water-soluble polymers, etc.), solubilizers (anionic surfactants, nonionic surfactants, amphoteric surfactants, etc.), solvents (purified water, etc.), polyols (glycerin, polyethylene glycol, etc.), and preservatives (ethyl parahydroxybenzoate, methyl parahydroxybenzoate, parahydroxybenzoate, parahydroxybenzoate, parahydroxybenzoate). Examples of ingredients include propyl oxybenzoate, butyl parahydroxybenzoate, etc., excipients (crystalline cellulose, lactose, mannitol, low-substituted hydroxypropyl cellulose, crospovidone, etc.), binders (starch, crystalline cellulose, etc.), film-forming agents (gelatin, glycerin, succinylated gelatin, pectin, etc.), bases (medium-chain triglyceride, rapeseed oil, etc.), suspending agents (beeswax, glycerin fatty acid ester, etc.), antioxidants, flavorings, cooling agents (menthol, etc.), colorants, pH adjusters, buffering agents, etc. If the ingestible / administered composition is a pharmaceutical or quasi-drug, it may contain a pharmacoactive ingredient in addition to the above-mentioned additives, or in addition to the above-mentioned additives. If the ingestible / administered composition is a food product, it may contain food ingredients in addition to or in addition to the above-mentioned additives. The food ingredients are not particularly limited and include water, grains, fruits, vegetables, meat, etc.

[0048] The content of any optional component in the ingestible / administered composition is determined appropriately, taking into consideration the type of infection-inhibiting composition, etc., and is determined, for example, within a range of 0 to 99.9% by mass relative to the total mass of the infection-inhibiting composition.

[0049] In addition to the infection inhibitor, the oral composition may optionally contain other known components as appropriate, depending on the dosage form, as long as they do not interfere with the effects of the present invention. If the oral composition is a toothpaste, it may contain abrasives, viscosity enhancers, binders, surfactants, and, if necessary, sweeteners, colorants, preservatives, fragrances, active ingredients, etc. If the oral composition is a mouthwash, it may contain viscosity agents, binders, surfactants, and, if necessary, sweeteners, colorants, preservatives, fragrances, active ingredients, etc. When the oral composition is in tablet form, it may contain sugar alcohols such as sorbitol and maltitol, excipients such as cellulose, lactose, and dextrin, fine silicon dioxide, acidulants, sweeteners, colorants, emulsifiers, thickeners, gelling agents, fruit juice, spices, active ingredients, and the like. If the oral composition is a gummy, it may contain thickeners and gelling agents such as glycerin and gelatin, sugars, acidulants, sweeteners, colorants, emulsifiers, fruit juice, active ingredients, etc. If the oral composition is chewing gum, it may contain a gum base, binders such as edible gum, sweeteners, colorants, acidulants, preservatives, glazing agents, flavorings, active ingredients, etc. If necessary, the chewing gum may be coated with a sugar coating.

[0050] Examples of abrasives include silica-based abrasives, calcium phosphate-based abrasives, and calcium carbonate-based abrasives. The amount of abrasive added is usually 2 to 50% by mass of the total mass of toothpaste, and 0 to 30% by mass of the total mass of liquid toothpaste. Examples of thickening agents include sugar alcohols such as sorbitol and xylitol, and polyhydric alcohols such as glycerin and propylene glycol. The amount of thickening agent added is usually 5 to 50% by mass of the total mass of the toothpaste. Examples of binders include cellulose derivatives such as sodium carboxymethylcellulose, gums such as xanthan gum, and organic or inorganic binders such as gelling silica and gelling aluminum silica. The amount of binder added is usually 0.5 to 10% by mass of the total mass of the toothpaste.

[0051] As surfactants, anionic surfactants, nonionic surfactants, cationic surfactants, and amphoteric surfactants commonly used in oral compositions can be included. Examples of anionic surfactants include alkyl sulfates such as sodium lauryl sulfate and N-acyl sarcosinates. Examples of nonionic surfactants include sugar fatty acid esters, sugar alcohol fatty acid esters, sorbitan fatty acid esters, glycerin fatty acid esters, polyoxyethylene fatty acid esters such as polyoxyethylene hydrogenated castor oil, polyoxyethylene higher alcohol ethers, and fatty acid alkanolamides. Examples of cationic surfactants include alkylammonium salts, and examples of amphoteric surfactants include betaine-based and imidazoline-based surfactants. The amount of surfactant included is usually preferably 0 to 10% by mass, and more preferably 0.01 to 5% by mass, relative to the total mass of the toothpaste.

[0052] Examples of sweeteners include sodium saccharin. Examples of coloring agents include Red No. 2, Blue No. 1, and Yellow No. 4, while examples of preservatives include parahydroxybenzoic acid esters. The fragrances include peppermint oil, spearmint oil, anise oil, eucalyptus oil, wintergreen oil, cassia oil, clove oil, thyme oil, sage oil, lemon oil, orange oil, peppermint oil, cardamom oil, coriander oil, mandarin oil, lime oil, lavender oil, rosemary oil, laurel oil, chamomile oil, caraway oil, marjoram oil, bay oil, lemongrass oil, origanum oil, pine needle oil, neroli oil, rose oil, jasmine oil, grapefruit oil, and Natural fragrances such as wheat oil, yuzu oil, iris concrete, absolute peppermint, absolute rose, and orange blossom, and fragrances obtained by processing these natural fragrances (cutting the pre-distillate, cutting the post-distillate, fractional distillation, liquid-liquid extraction, essence production, powder production, etc.), and menthol, carvone, anethole, cineole, methyl salicylate, cinnamic aldehyde, eugenol, 3-l-mentoxypropane-1,2-diol, thymol, linalool, linali Examples of individual fragrances include ethyl acetate, limonene, menthone, menthyl acetate, N-substituted paramenthane-3-carboxamide, pinene, octyl aldehyde, citral, pulegone, carbyl acetate, anisaldehyde, ethyl acetate, ethyl butyrate, allylcyclohexanepropionate, methyl anthranilate, ethyl methylphenyl glycidate, vanillin, undecalactone, hexanal, butanol, isoamyl alcohol, hexenol, dimethyl sulfide, cyclotene, furfural, trimethylpyrazine, ethyl lactate, ethyl thioacetate, and other single fragrances, as well as blended fragrances such as strawberry, apple, banana, pineapple, grape, mango, butter, milk, fruit mix, and tropical fruit flavors. Known fragrance materials used in oral compositions can be used. The amount of these fragrances is usually 0.00001 to 1% by mass relative to the total mass of the toothpaste or mouthwash. Furthermore, the amount of these fragrances is 0.001 to 50% by mass relative to the total mass of the tablets, gummies, or chewing gum. It is preferable to use 0.1 to 10% of the above-mentioned fragrance materials in the oral composition.

[0053] The oral composition may contain active ingredients other than the infection inhibitor of the present invention. Other active ingredients may include known ingredients commonly used in oral compositions, provided they do not interfere with the effects of the present invention. Examples of active ingredients include nonionic disinfectants such as isopropylmethylphenol, cationic disinfectants such as benzalkonium chloride, anti-inflammatory agents such as tranexamic acid and epsilon-aminocaproic acid, enzymes such as dextranase, fluorides such as sodium fluoride and sodium monofluorophosphate, water-soluble phosphate compounds, copper compounds, potassium nitrate, aluminum lactate, various vitamins, and plant extracts. The amount of each active ingredient is set within a range that does not interfere with the effects of the infection inhibitor of the present invention.

[0054] <Method for producing infection-inhibiting compositions> The manufacturing method for ingestible / administered compositions is determined by conventionally known manufacturing methods, depending on the type and dosage form of the ingestible / administered composition. One method for producing a solid ingestible or administered composition is to mix an infection inhibitor with optional components as needed, and then mold the mixture into a desired dosage form (powder, granules, capsules, tablets, etc.). One method for producing a liquid ingestible / administered composition is to disperse an infection inhibitor and, if necessary, an optional component in a solvent.

[0055] Methods for producing oral compositions include mixing an infection inhibitor with optional components as needed, or dispersing them in a solvent.

[0056] <Method of using infection-inhibiting compositions> If the infection-inhibiting composition is an ingestible or administered composition, the method of use (ingestion or administration) of the infection-inhibiting composition shall be appropriately determined according to the type of infection inhibitor, the dosage form of the infection-inhibiting composition, etc. For example, it is preferable to ingest or administer the ingestible / administered composition once to ten times a day, such that the daily intake / administration amount falls within the range of the preferred intake / administration amount for each infection inhibitor.

[0057] If the infection-inhibiting composition is an oral composition, the method of use of the oral composition will be determined appropriately according to the type of infection-inhibiting agent, the dosage form of the oral composition, etc. For example, it is preferable to use the oral composition for oral treatment 1 to 10 times a day, so that the daily amount used allows for intake within the preferred intake / administration range of each infection inhibitor. [Examples]

[0058] The present invention will be described in detail below with reference to examples, but the present invention is not limited to the following description. In Tables 1 and 2, "%" represents "mass%" unless otherwise specified.

[0059] (Raw materials used) Table 1 lists the components used in the evaluation (evaluation components). In the table, Nos. 1-17 are infection inhibitors. Nos. 18-19 are comparative components of the infection inhibitors.

[0060] (Examples 1-29, Comparative Examples 1-4) According to Table 1, each evaluation component was dispersed in a solvent to obtain infection-inhibiting compositions at the concentrations shown in the table. The infection-inhibiting effect of the obtained infection-inhibiting compositions was evaluated.

[0061] (Infection control effect) • SARS-CoV-2 virus suspension: 2019-nCoV / Japan / AI / I-004 / 2020 strain (as described in the National Institute of Infectious Diseases distribution approval document dated March 2nd). Infectivity titer was determined using the TCID50 method with the following cells. • Cells infected with the SARS-CoV-2 virus: "Vero E6" (kidney-derived cells from African green monkeys) are strongly expressed with TMPRSS2 to enable efficient infection with SARS-CoV-2 (VeroE6+TMPRSS2).

[0062] <Evaluation Procedure> The day the virus was introduced was designated as Day 0. • Day 1 (the day before Day 0) VeroE6+TMPRSS2(5×10 4 Cells (100 μL / 96 wells) were seeded into 96-well plates and cultured in a CO2 incubator (37°C, 5% CO2 / 95% air). The culture medium was Dulbecco's modified Eagle's minimum essential medium (DMEM) (Nissui Pharmaceutical Co. Ltd., Tokyo, Japan) supplemented with G418 disulfate (1 mg / mL), penicillin (100 units / mL), streptomycin (100 μg / mL), and 5% fetal bovine serum. Day 0 (1) 2 μL of the infection-suppressing composition for each case, diluted with MS (DMEM supplemented with 0.5% FBS), was placed in the 96 wells of another plate. 200 μL of virus solution was added to each of the 96 wells of this plate, and the mixture was allowed to stand for 5 minutes to obtain a mixture of the infection-suppressing composition and virus for each case. (2) The culture medium of the cells seeded in the 96-well plate was removed. (3) Immediately add 100 L of the mixture prepared in (1) to each well of the plate after treatment in (2), and incubate (37°C, 5 vol% CO2 / 95 vol% air). Day 3 (1) After culturing, 100 μL of glutaraldehyde (fixative) was added to each well of the plate and left to stand for 30 minutes to fix the cells. (2) Remove the fixative added in (1) and wash with tap water. (3) After (2), 1% by mass of crystal violet solution (staining solution) was added to each well and allowed to stand for 30 minutes to stain. (4) Remove the staining solution added in (3), wash with tap water, and dry. (5) The OD570 of the contents of each well was measured using a plate reader. Based on the OD570 measurement, the infection suppression rate was calculated and evaluated according to the evaluation criteria below.

[0063] ≪Evaluation Criteria≫ 〇: Infection suppression rate of 50% or more. △: Infection suppression rate greater than 0% but less than 50%. ×: Infection suppression rate 0%.

[0064] [Table 1]

[0065] [Table 2]

[0066] As shown in Table 2, all of the Examples 1 to 29 to which the present invention was applied showed an inhibitory effect on SARS-CoV-2 virus infection. Comparative Examples 1 to 4, which used extracts other than the infection inhibitor of the present invention, did not show any effect in suppressing SARS-CoV-2 virus infection. From these results, it has been confirmed that applying the present invention can suppress infection by the SARS-CoV-2 virus. However, Examples 1-25, 28, and 29 are for reference only.

Claims

1. A composition for inhibiting SARS-CoV-2 virus infection, containing as an active ingredient a rooibos extract which is an aqueous extract containing 0.24 to 0.32% by mass of eriodictiol-6-C-glucoside, which is a SARS-CoV-2 virus infection inhibitor.

2. A composition for suppressing SARS-CoV-2 virus infection according to claim 1, which is a pharmaceutical product, a quasi-drug, a food product, or an oral care product.

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