virus inactivating agents

Abstract

To provide a virus inactivator that can inactivate virus in an environment.SOLUTION: A virus inactivator comprises 2-(4-methylphenyl) acetaldehyde as an active ingredient.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to a virus inactivating agent that inactivates viruses. [Background technology]

[0002] Viral infections are diseases that cause cold-like symptoms as well as severe symptoms such as pneumonia, hepatitis, and encephalitis, and are a perpetual threat to humanity. In recent years, influenza viruses have wreaked havoc around the world, and sometimes pandemics can occur due to the emergence of new strains of influenza with antigenic changes. In 2019, SARS-CoV-2 emerged, causing a pandemic that has not only affected lives and health but also economic activity and social functions.

[0003] To deal with this situation, vaccines and antiviral drugs are being developed, but the development of vaccines and drugs takes time and is not always successful. When a virus is brought into a living space by an infected person, the infection spreads either directly from the patient or through the environment, including clothing, various tools and components, walls, air conditioners, etc. Therefore, it is thought that effective ways to prevent the spread of infection are to remove or inactivate the virus by washing and disinfecting hands, clothing, and various tools and components that the virus may come into contact with, as well as to inactivate viruses that are dispersed into living spaces or floating in the air as aerosols.

[0004] Traditionally, ethanol, sodium hypochlorite, chlorine dioxide, glutaraldehyde, etc. have been used to inactivate viruses. However, these common disinfectants are highly irritating to mucous membranes and skin, and their use is limited due to safety concerns. Furthermore, spraying chlorine dioxide has been devised as a method to chemically inactivate viruses present in air, but its effectiveness is uncertain.

[0005] Essential oils and the aromatic compounds they contain are used as fragrances in a variety of products, including cosmetics, and it is well known that some essential oils and fragrance compounds have specific physiological effects. For example, there are many essential oils and fragrance compounds that have antiviral activity against viruses (e.g., Patent Document 1, Non-Patent Document 1, Non-Patent Document 2). [Prior art documents] [Patent documents]

[0006] [Patent Document 1] Japanese Patent Application Publication No. 5-306217 [Non-patent literature]

[0007] [Non-Patent Document 1] Swamy et al., Evid Based Complement Alternat Med. 2016:3012462. [Non-patent document 2] Hayashi K, et al., Planta Medica, 01 Jun 1995, 61(3):237-241 Summary of the Invention [Problem to be solved by the invention]

[0008] The present invention relates to providing a virus inactivating agent that is capable of inactivating viruses present in the environment. [Means for solving the problem]

[0009] The present inventors have found that certain fragrance compounds have the effect of inactivating influenza viruses and are useful as virus inactivating agents.

[0010] That is, the present invention relates to the following 1) and 2). 1) A virus inactivator whose active ingredient is 2-(4-methylphenyl)acetaldehyde. 2) A method for inactivating viruses, which comprises applying 2-(4-methylphenyl)acetaldehyde or a composition containing same to an object suspected of being contaminated with a virus. [Effects of the Invention]

[0011] The virus inactivating agent of the present invention can inactivate viruses attached to hard or soft surfaces in the living environment, viruses dispersed in droplets in living spaces, and viruses floating in the air as aerosols, thereby preventing or reducing the spread of infection caused by these viruses. [Brief explanation of the drawings]

[0012] [Figure 1] Influenza virus inactivation effect (gas phase). [Figure 2] Influenza virus inactivation effect (liquid phase). DETAILED DESCRIPTION OF THE INVENTION

[0013] The 2-(4-methylphenyl)acetaldehyde of the present invention is a compound used as a fragrance, and a 50% solution of 2-(4-methylphenyl)acetaldehyde obtained by dissolving 2-(4-methylphenyl)acetaldehyde in 2-phenylethanol and (4-methylphenyl)ethanol (50% 2-(4-methylphenyl)acetaldehyde, approximately 25% (4-methylphenyl)ethanol, approximately 25% 2-phenylethanol) is commercially available from Givaudan under the name "Syringa Aldehyde 50%." In the present invention, the 2-(4-methylphenyl)acetaldehyde used may be "Syringa Aldehyde 50%." Alternatively, 2-(4-methylphenyl)acetaldehyde sold as a reagent may be used. Alternatively, 2-(4-methylphenyl)acetaldehyde separated from Syringa Aldehyde 50% by column chromatography or distillation may be used.

[0014] The 2-(4-methylphenyl)acetaldehyde of the present invention can be used in either a liquid or gas phase, but is preferably used in a gas phase from the viewpoint of virus inactivation effect.

[0015] The viruses that are the target of the virus inactivating agent of the present invention include all types of viruses, regardless of the type of nucleic acid (RNA, DNA) and whether or not they have an envelope. Examples of enveloped viruses include influenza virus, coronavirus, SARS coronavirus, SARS coronavirus-2, respiratory syncytial virus, mumps virus, Lassa virus, dengue virus, rubella virus, and human immunodeficiency virus, which have RNA as their nucleic acid, and human herpes virus, vaccinia virus, and hepatitis B virus, which have DNA as their nucleic acid. Non-enveloped viruses include norovirus, poliovirus, echovirus, hepatitis A virus, hepatitis E virus, rhinovirus, astrovirus, rotavirus, coxsackievirus, enterovirus, and sapovirus, which have RNA as nucleic acid, and adenovirus, B19 virus, papovavirus, and human papillomavirus, which have DNA as nucleic acid.

[0016] Among these, viruses having an envelope are preferred, viruses having an envelope and having RNA as nucleic acid are more preferred, and influenza virus, human coronavirus, SARS coronavirus, and SARS coronavirus-2 are more preferred. SARS-CoV-2 (Severe acute respiratory syndrome coronavirus 2) is a SARS-related coronavirus that causes acute respiratory disease (COVID-19).

[0017] In the present invention, inactivation of a virus means the action of reducing or eliminating the activity of the virus and eliminating its infectivity to host cells. The virus inactivation effect can be confirmed, for example, by contacting a test product with a virus, infecting host cells with the virus, and measuring the virus infectivity. The host cells may be any cells in which the target virus can grow. For influenza virus, for example, canine kidney cells (MDCK), African green monkey kidney epithelial cells (Vero), or a duck embryonic stem cell-derived cell line (EB66) can be used. For human coronavirus, for example, human ileocecal adenocarcinoma cells (HCT-8), African green monkey kidney epithelial cells (VeroE6), or a human liver cancer-derived cell line (Huh7) can be used.

[0018] As shown in the examples described below, when a cotton ball soaked in 2-(4-methylphenyl)acetaldehyde of the present invention or a composition containing the same is placed in a glass bottle and the bottle is filled with the compound, dried influenza viruses are added, and the compound and the virus are allowed to come into contact with each other in the gas phase at room temperature, the viral infectious titer is reduced by 99.99% or more. Therefore, 2-(4-methylphenyl)acetaldehyde can be a virus inactivating agent, preferably a virus inactivating agent that inactivates viruses in the gas phase. Alternatively, 2-(4-methylphenyl)acetaldehyde can be used to produce a virus inactivating agent, preferably a virus inactivating agent that inactivates viruses in the gas phase. 2-(4-methylphenyl)acetaldehyde can also be used to inactivate viruses, preferably in the vapor phase.

[0019] The virus inactivating agent of the present invention may be in the form of 2-(4-methylphenyl)acetaldehyde used alone, or may be in the form of a composition containing it (for example, an antiviral composition, a sanitary product composition, etc.). That is, the virus inactivating agent of the present invention can be used as an antiviral composition that exhibits a virus inactivating effect or a sanitary product composition that exhibits an antiviral effect, or as a material or preparation to be incorporated into these.

[0020] The antiviral compositions described above include those used in a liquid or gaseous phase. Antiviral compositions used in a liquid phase may contain, in addition to 2-(4-methylphenyl)acetaldehyde, antibacterial substances such as hypochlorous acid, hydrogen peroxide, and silver ion compounds, cationic antibacterial agents (e.g., benzethonium chloride), disinfectants (e.g., triclosan and isopropylmethylphenol), ethanol, surfactants, and the like. They are prepared by appropriately blending additives such as chelating agents, humectants, lubricants, builders, buffers, abrasives, electrolytes, bleaches, fragrances, dyes, foam control agents, corrosion inhibitors, essential oils, thickeners, pigments, gloss enhancers, enzymes, detergents, solvents, dispersants, polymers, silicones, and hydrotropic substances. The form of such compositions may be, but is not limited to, liquid, emulsion, cream, lotion, paste, gel, sheet (supported by a substrate), oil, and the like. The antiviral composition can be used by being appropriately blended with various detergents (laundry detergents, household detergents, dish detergents, hair washes, hand washes, body washes, etc.), disinfectants, etc.

[0021] Antiviral compositions used in a gaseous state (e.g., compositions for removing viruses in space) may be in liquid or gel form, with liquid being preferred. The composition can be prepared by blending 2-(4-methylphenyl)acetaldehyde with a base material and various additives (polyols (dipropylene glycol, propylene glycol, etc.), surfactants, UV absorbers, antioxidants, preservatives, deodorants, natural extracts, silicones, thickeners, dyes, pigments, coloring materials, oils, fragrances, etc.). Examples of bases include conventionally known ones, whether oil-based or water-based, such as water, methanol, ethanol, propanol, isopropanol, butanol, isobutanol, dimethyl ether, liquid propane, petrolatum, lanolin, castor oil, and paraffinic hydrocarbons (e.g., liquid paraffin), which may be used alone or in combination of two or more. When preparing a gel preparation, it can be prepared by appropriately adding a natural or synthetic gelling agent, for example, a water-soluble gelling agent such as carrageenan or gellan gum, or an oil-soluble gelling agent such as metal soap or aluminum octylate, according to a conventionally known method.

[0022] Examples of the hygiene product compositions include lotions, creams, shampoos, hair conditioners, hand soaps, shampoos, body shampoos, facial cleansers, bath additives, foams, antiperspirants, deodorants, anti-armpit odor agents, and oral hygiene products (mouthwashes, toothpastes, mouth fresheners, mouthwashes, etc.). The composition can be prepared by a conventional method by appropriately combining carriers acceptable for use in cosmetics, etc. (e.g., diluents, dispersants, buffers, pH adjusters, dispersants, emulsifiers, surfactants, preservatives, stabilizers, antioxidants, colorants, moisturizers, thickeners, disinfectants, fragrances, etc.).

[0023] In embodiments in which the virus inactivating agent of the present invention is used as a composition, the content of the active ingredient can be appropriately determined depending on the form of the composition. For example, the content of 2-(4-methylphenyl)acetaldehyde relative to the total amount of the composition is preferably 0.001% by mass or more, more preferably 0.01% by mass or more, and even more preferably 0.1% by mass or more. It is also preferably 99.999% by mass or less, more preferably 50% by mass or less, and even more preferably 10% by mass or less. It is also preferably 0.001 to 99.999% by mass, more preferably 0.01 to 50% by mass, and even more preferably 0.1 to 10% by mass.

[0024] The virus inactivating agent of the present invention can inactivate viruses attached to the skin or mucous membranes of animals contaminated with viruses or to hard or soft surfaces of inanimate objects, or viruses splashed into living spaces. Examples of inanimate surfaces include hard surfaces in homes and business facilities, such as counters, sinks, restrooms, toilets, bathtubs, shower basins, floors, windows, doorknobs, walls, sewer outlets, and pipes; hard surfaces of various appliances, tools, and miscellaneous items, such as kitchenware, furniture, telephones, and toys; and soft surfaces, such as textile products (carpets, area rugs, curtains, fabric furniture, and clothing). Examples of living spaces include dining rooms, bedrooms, children's rooms, bathrooms, and toilets in ordinary homes; stores, restaurants, inns, hospitals, workshops, factories, and other facilities; vehicles, such as automobiles, trains, and airplanes; and semi-enclosed spaces (lockers, storage rooms, closets, and other spaces).

[0025] In the virus inactivating agent of the present invention, 2-(4-methylphenyl)acetaldehyde or a composition containing same is applied to an object where viral contamination is a concern, but the mode of application is not particularly limited, and 2-(4-methylphenyl)acetaldehyde or a composition containing same may be brought into contact with or react with viruses in the gas phase or liquid phase. Methods for bringing 2-(4-methylphenyl)acetaldehyde into contact with viruses in the liquid phase include applying 2-(4-methylphenyl)acetaldehyde or a composition containing same directly to the object to be treated, diffusing 2-(4-methylphenyl)acetaldehyde or a composition containing same and sprinkling it on the object to be treated, or wiping the surface of the object with a sheet, gauze, towel, wet towel, tissue, wet tissue, or the like impregnated with 2-(4-methylphenyl)acetaldehyde or a composition containing same. Furthermore, by filling 2-(4-methylphenyl)acetaldehyde or a composition containing it into a container or device for atomization or diffusion, such as a pressurized liquid atomizing spray, a pressurized air atomizing spray device, a diffuser, or a nebulizer, and dispersing it in mist form into a space where viruses are present, the rate of volatilization can be increased, and the virus inactivation effect can be rapidly exerted. Similar effects can also be achieved when 2-(4-methylphenyl)acetaldehyde or a composition containing it is used in the form of an aerosol, mist spray, etc.

[0026] The method of contacting or reacting 2-(4-methylphenyl)acetaldehyde or a composition containing it with viruses in the gas phase may be either a method of naturally volatilizing 2-(4-methylphenyl)acetaldehyde or a method of forced volatilization. If 2-(4-methylphenyl)acetaldehyde is naturally volatilized, viruses present in the space can be inactivated simply by leaving it in a living space, allowing for easy virus removal (virus removal) from the space. When the virus inactivating agent of the present invention is used for the purpose of natural volatilization, conventionally known methods can be used, such as a method of impregnating a core rod, filter paper, or the like with 2-(4-methylphenyl)acetaldehyde or a composition containing it and volatilizing it, or a method of volatilizing it using a permeable membrane. Also, 2-(4-methylphenyl)acetaldehyde or a composition containing it can be kneaded with a resin and used. Examples of resins that can be kneaded include natural, petroleum, and synthetic waxes, rosin-based resins, ethylene-vinyl acetate copolymers, ethylene-vinyl alcohol copolymers, polyesters, polyolefins, and acrylic resins. The kneaded product can be used as is, or it can be supported on a porous carrier, made into a sheet, or the sheet can be used as a laminate. Examples of porous carriers include natural polymers such as cellulose and chitosan, the above-mentioned synthetic resins, and inorganic porous materials such as calcium silicate, which can be formed into any shape, such as granules or sheets. The above-mentioned kneaded product or laminate can be used by gradually volatilizing 2-(4-methylphenyl)acetaldehyde by placing it in, for example, air conditioning equipment, toilets, bathrooms, living rooms, hospital rooms, hospital waiting rooms, dustbins, etc. 2-(4-methylphenyl)acetaldehyde or a composition containing it can also be used by being supported on a product made of paper, nonwoven fabric, etc. (e.g., an air purifier filter). When 2-(4-methylphenyl)acetaldehyde is used after forced evaporation, examples of such a method include a method of evaporating it using a fan, a method of evaporating it by heating using a heater, and a method of evaporating it by ultrasound.

[0027] When performing space virus removal treatment, the amount of 2-(4-methylphenyl)acetaldehyde or a composition containing it used can be adjusted appropriately depending on the treatment method, the space environment such as temperature and humidity, the vapor pressure of 2-(4-methylphenyl)acetaldehyde, etc., and it is possible to use 2-(4-methylphenyl)acetaldehyde at a concentration equal to or greater than the saturation concentration in the space. For example, the concentration of 2-(4-methylphenyl)acetaldehyde in the target space is 0.1% or more, preferably 1% or more, more preferably 5% or more, and even more preferably 10% or more of the saturation concentration of the compound in the space, and is preferably used so that it volatilizes at 100% or less, more preferably 50% or less, and more preferably 25% or less. The concentration of 2-(4-methylphenyl)acetaldehyde in a target space can be detected by measuring the concentration of the compound in gas collected from the space. Methods include using a volatile organic compound concentration measuring device (VOC measuring device, odor sensor, etc.), or using gas chromatography or gas chromatography / mass spectrometry in combination with a gas collection tube.

[0028] In relation to the above-described embodiment, the present invention further discloses the following aspects. <1> A virus inactivator whose active ingredient is 2-(4-methylphenyl)acetaldehyde. <2> Use of 2-(4-methylphenyl)acetaldehyde for producing a virus inactivating agent. <3> Use of 2-(4-methylphenyl)acetaldehyde or a composition containing same for inactivating viruses. <4> A method for inactivating viruses, comprising applying 2-(4-methylphenyl)acetaldehyde or a composition containing same to an object suspected of being contaminated with a virus. <5> <1> ~ <4> In the present invention, the virus is preferably an enveloped RNA virus. <6> <1> ~ <4> In the method, the virus is preferably an influenza virus or a coronavirus. <7> <1> ~ <6> In the method, the inactivation of viruses is preferably inactivation of viruses in the gas phase. <8> <1> ~ <7> In the composition containing 2-(4-methylphenyl)acetaldehyde, the content of the 2-(4-methylphenyl)acetaldehyde relative to the total amount of the composition is preferably 0.001% by mass or more, more preferably 0.01% by mass or more, even more preferably 0.1% by mass or more, and is preferably 99.999% by mass or less, more preferably 50% by mass or less, even more preferably 10% by mass or less, or is preferably 0.001 to 99.999% by mass, more preferably 0.01 to 50% by mass, even more preferably 0.1 to 10% by mass. <9> The 2-(4-methylphenyl)acetaldehyde or a composition containing the same is used so that the concentration of the 2-(4-methylphenyl)acetaldehyde in the target space is 0.1% or more, preferably 1% or more, more preferably 5% or more, and even more preferably 10% or more of the saturated concentration of the compound in the space, and is preferably volatilized at 100% or less, more preferably 50% or less, and more preferably 25% or less. <4> How to do it. [Example]

[0029] The present invention will be described in more detail below with reference to examples. Example 1: Inactivation of influenza virus in the gas phase by fragrance compounds 1. Method The influenza virus type A (A / Puerto Rico / 8 / 1934, H1N1) strain was used as the test virus strain. The flavor compounds used were either 50% Syringe Aldehyde (Givaudan; 50% solution of 2-(4-methylphenyl)acetaldehyde), or 2-(4-methylphenyl)acetaldehyde obtained by separating Syringe Aldehyde using silica gel column chromatography (eluent: hexane / ethyl acetate = 85 / 15 (v / v)), or mineral oil (75 μL). A cotton ball was soaked in the cotton ball and attached to the lid of a 15 mL glass bottle (Maruem Co., Ltd.) with double-sided tape, which was then sealed and allowed to fill the bottle for 30 minutes. The saturated vapor pressure concentration of 2-(4-methylphenyl)acetaldehyde (calculated using the Estimation Program Interface Suite (EPI Suite, https: / / www.epa.gov / tsca-screening-tools / epi-suitetm-estimation-program-interface) at 25°C and the saturated vapor pressure concentration at standard atmospheric pressure (101,325 Pa)) is 108.9 ppmv. Influenza virus 1.5 μL (8.3 × 10 5 The virus-infected virus (FFU) was allowed to dry on the lid of a cryovial (Thermo Fisher Scientific) for 30 minutes. The lid of the vial with the virus attached was placed in a glass bottle, and the fragrance compounds and virus were allowed to react for 30 minutes at room temperature (approximately 23°C). The fragrance compounds were placed on the lid of the bottle, and the virus on the bottom of the bottle, ensuring no direct contact between the fragrance compounds and the virus. After the reaction, the virus was recovered using Hybridoma-SFM medium (Thermo Fisher Scientific) and inoculated into MDCK cells (derived from canine kidney tubular epithelial cells) that had been cultured in a 12-well plate. After approximately 18 hours of incubation at 37°C and 5% CO2, the number of foci formed was counted, and the virus infectivity titer was determined. The infectivity titer when reacted with the control mineral oil was set at 100%, and the virus inactivation activity of each fragrance compound was calculated. The test was performed in triplicate.

[0030] 2.Results As shown in Figure 1, compared to the control mineral oil, 2-(4-methylphenyl)acetaldehyde reduced the detectable virus load to 0.10%, and Syringa Aldehyde 50% reduced the detectable virus load to 0.008%.

[0031] Example 2: Inactivation of influenza virus in liquid phase by fragrance compounds 1. Method Influenza virus type A (A / Puerto Rico / 8 / 1934, H1N1) strain was used as the test virus strain. Syringa Aldehyde 50% (Givaudan; 50% solution of 2-(4-methylphenyl)acetaldehyde) was used as a flavor compound. 2-(4-methylphenyl)acetaldehyde obtained by separating this using silica gel column chromatography (developing solvent: hexane / ethyl acetate = 85 / 15 (v / v)) was then dissolved in Hybridoma-SFM medium (Thermo Fisher Scientific) containing 1% (v / v) dipropylene glycol as a solvent so that the final concentration upon reaction with the virus was 0.1% (v / v). The flavor compound solution or 1% (v / v) dipropylene glycol solution was mixed with an influenza virus solution (8.3 × 10 5 60 μL of each (FFU) was added to a 96-well plate and incubated at room temperature (approximately 23°C) for 30 minutes. After incubation, the virus was diluted with medium and inoculated into MDCK cells (derived from canine kidney tubular epithelial cells) that had been previously cultured in a 48-well plate. After incubation at 37°C and 5% CO2 for approximately 18 hours, the number of foci formed was counted and the viral infectivity titer was determined. The infectivity titer when reacted with the control 1% (v / v) dipropylene glycol solution was set at 100%, and the viral infectivity titer of each fragrance compound was calculated. The test was performed in triplicate.

[0032] 2.Results As shown in Figure 2, compared to the control 1% dipropylene glycol solution, 2-(4-methylphenyl)acetaldehyde reduced the detectable virus load to 0.8%, and 50% Syringe Aldehyde reduced the detectable virus load to 2.7%.

Claims

1. An influenza virus inactivating agent containing 2-(4-methylphenyl)acetaldehyde as an active ingredient.

2. The agent according to claim 1, which inactivates influenza viruses in the gas phase.

3. A method for inactivating influenza viruses, comprising applying a composition containing 0.01% by mass or more of 2-(4-methylphenyl)acetaldehyde to a subject (excluding humans) concerned about contamination with influenza viruses.

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