Virus inactivator

Abstract

To provide a virus inactivator that can inactivate virus in an environment.SOLUTION: A virus inactivator comprises at least one compound selected from formic acid 2-phenylethyl, benzyl acetate, methoxy citronellal, cinnamyl alcohol, hydratropic alcohol, dimethylbenzyl carbinol, trans-2-hexene-1-ol, trans-3-hexenol, cis-3-hexenol and 3-phenylpropionaldehyde as an active ingredient.SELECTED DRAWING: None

Description

Technical Field

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

[0002] Viral infectious diseases are pathologies that cause symptoms ranging from cold-like symptoms to severe conditions such as pneumonia, hepatitis, and encephalitis, and have been a perpetual threat to humanity. In recent years, influenza viruses have spread globally, and pandemics may sometimes occur due to the emergence of novel influenza with altered antigenicity. Furthermore, in 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged and caused a pandemic, affecting not only human life and health, but also economic activities and social functions.

[0003] To respond to such situations, efforts have been made to develop vaccines and antiviral agents, but the development of vaccines and therapeutic agents takes time and cannot be guaranteed to be successful. When viruses are brought into living spaces by infected individuals, infection spreads directly from the patient or indirectly via the environment including clothing, various instruments and members, walls, equipment such as air conditioners, and the like. Therefore, it is considered effective for preventing the spread of infection to remove or inactivate viruses by cleaning and disinfecting fingers, hands, clothing, and various instruments and members that viruses may adhere to, and to inactivate viruses splashed into living spaces and viruses floating in the air as aerosols.

[0004] Conventionally, ethanol, sodium hypochlorite, chlorine dioxide, glutaraldehyde and the like have been used for the purpose of inactivating viruses. However, these common disinfectants are highly irritating to mucous membranes and skin, so their uses are limited due to safety concerns. Additionally, as a method for chemically inactivating viruses present in spaces, spraying chlorine dioxide has been proposed, but its effect is not conclusive.

[0005] Essential oils and the aromatic components they contain are used as fragrances in a variety of products, including cosmetics, but it is also well known that some essential oils and fragrance compounds exhibit specific physiological effects. For example, there are many essential oils and fragrance compounds that have antiviral activity against viruses (see, for example, 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 [Overview of the project] [Problems that the invention aims to solve]

[0008] The present invention relates to providing a virus inactivator that enables the inactivation of viruses present in the environment. [Means for solving the problem]

[0009] The inventors have discovered that certain fragrance compounds have the effect of inactivating influenza viruses, and that these are useful as virus inactivators.

[0010] In other words, the present invention relates to the following 1) to 2). 1) A virus inactivator comprising one or more compounds selected from 2-phenylethyl formate, benzyl acetate, methoxycitronellal, cinnamyl alcohol, hydratropic alcohol, dimethylbenzylcarbinol, trans-2-hexen-1-ol, trans-3-hexenol, cis-3-hexenol, and 3-phenylpropionaldehyde as an active ingredient. 2) A method for inactivating viruses, comprising applying one or more compounds selected from 2-phenylethyl formate, benzyl acetate, methoxycitronellal, cinnamyl alcohol, hydratropic alcohol, dimethylbenzylcarbinol, trans-2-hexen-1-ol, trans-3-hexenol, cis-3-hexenol, and 3-phenylpropionaldehyde, or a composition containing the same, to an object suspected of viral contamination. [Effects of the Invention]

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

[0012] [Figure 1] Influenza virus inactivation effect (gas phase). [Figure 2] Influenza virus inactivation effect (liquid phase). [Modes for carrying out the invention]

[0013] The compounds of the present invention, 2-phenylethyl formate, benzyl acetate, methoxycitronellal, cinnamyl alcohol, hydratropic alcohol, dimethylbenzylcarbinol, trans-2-hexen-1-ol, trans-3-hexenol, cis-3-hexenol, and 3-phenylpropionaldehyde (hereinafter also referred to as "the compounds of the present invention"), are all compounds used as fragrances and are commercially available as follows. ·2-Phenylethyl formate (alias: 2-Phenylethyl formate): Sigma-Aldrich, Tokyo Chemical Industry Co., Ltd. ·Benzyl acetate: Tokyo Chemical Industry Co., Ltd., Sigma-Aldrich ·Methoxycitronellal (alias: 7-methoxy-3,7-dimethyloctanal): Fujifilm Wako Pure Chemical Corporation ·Cinnamyl alcohol (alias: 3-phenyl-2-propen-1-ol): Fujifilm Wako Pure Chemical Corporation, Sigma-Aldrich ·Hydratropic alcohol (alias: 2-phenylpropan-1-ol): Tokyo Chemical Industry Co., Ltd., Sigma-Aldrich ·Dimethylbenzylcarbinol (alias: 2-methyl-1-phenylpropan-2-ol): Sigma-Aldrich, Tokyo Chemical Industry Co., Ltd. ·trans-2-hexen-1-ol (alias: (E)-2-hexen-1-ol): Sigma-Aldrich, Tokyo Chemical Industry Co., Ltd. ·trans-3-hexenol (alias: (E)-3-hexen-1-ol): Sigma-Aldrich ·cis-3-hexenol (alias: (Z)-3-hexen-1-ol): Sigma-Aldrich, Tokyo Chemical Industry Co., Ltd. ·3-phenylpropionaldehyde (alias: 3-phenylpropanal): Tokyo Chemical Industry Co., Ltd.

[0014] These compounds may be used alone or in a mixture of two or more thereof.

[0015] Among the compounds of the present invention, preferred compounds are, from the viewpoint of virus inactivation effect, trans-2-hexen-1-ol, trans-3-hexenol, cis-3-hexenol, and 3-phenylpropionaldehyde; from the viewpoints of scent intensity, quality, and volatility, hydratropic alcohol, dimethylbenzylcarbinol, 2-phenylethyl formate, benzyl acetate, methoxycitronellal, and cinnamyl alcohol; and comprehensively, 2-phenylethyl formate, benzyl acetate, methoxycitronellal, cinnamyl alcohol, hydratropic alcohol, and dimethylbenzylcarbinol.

[0016] The compound of the present invention can be used in either a liquid phase state or a gas phase state, but is preferably used in a gas phase state from the viewpoint of the virus inactivation effect.

[0017] Viruses targeted by the virus inactivating agent of the present invention include all types of viruses, regardless of the type of nucleic acid (RNA, DNA) and the presence or absence of an envelope. Examples of enveloped viruses include: RNA nucleic acid-containing viruses: influenza virus; coronavirus; SARS coronavirus; SARS coronavirus-2; respiratory syncytial virus; mumps virus; Lassa virus; dengue virus; rubella virus; human immunodeficiency virus; and DNA nucleic acid-containing viruses: human herpesvirus; vaccinia virus; hepatitis B virus; and the like. Examples of non-enveloped viruses include: RNA nucleic acid-containing viruses: norovirus; poliovirus; echovirus; hepatitis A virus; hepatitis E virus; rhinovirus; astrovirus; rotavirus; coxsackievirus; enterovirus; sapovirus; and DNA nucleic acid-containing viruses: adenovirus; B19 virus; papovavirus; human papillomavirus; and the like.

[0018] Of these, viruses having an envelope are preferred, viruses having an envelope and RNA as their nucleic acid are more preferred, influenza virus, human coronavirus, SARS coronavirus, SARS coronavirus-2 are more preferred, and influenza virus is even more preferred. SARS-CoV-2 (Severe acute respiratory syndrome coronavirus 2) is a SARS-related coronavirus that causes acute respiratory illness (COVID-19).

[0019] In the present invention, virus inactivation means reducing or eliminating the activity of the virus and thereby eliminating its ability to infect host cells. The virus inactivation effect can be confirmed, for example, by bringing the test product into contact with the virus, infecting host cells with the virus, and measuring the viral infectivity titer. Here, the host cell can be any cell in which the target virus can proliferate. For influenza virus, for example, canine kidney cells (MDCK), African green monkey kidney epithelial cells (Vero), or duck embryonic stem cell-derived cell lines (EB66) can be used. For human coronavirus, for example, human ileocecal adenocarcinoma cells (HCT-8), African green monkey kidney epithelial cells (VeroE6), or human liver cancer-derived cell lines (Huh7) can be used.

[0020] As shown in the examples described later, when the compound of the present invention, soaked into a cotton ball, is placed in a glass bottle and filled to capacity, and then dried influenza virus is added, and the compound and virus are brought into contact in the gas phase at room temperature, the viral infectivity titer is reduced by 99.7% or more. Therefore, the compounds of the present invention can serve as virus inactivators, preferably virus inactivators that inactivate viruses in the gas phase. Alternatively, the compounds of the present invention can be used to produce virus inactivators, preferably virus inactivators that inactivate viruses in the gas phase. Furthermore, the compounds of the present invention can be used to inactivate viruses, preferably in the gas phase.

[0021] The virus inactivating agent of the present invention may be used in the form of the compound of the present invention alone, or it 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 may be an antiviral composition that exhibits a virus inactivating effect, a sanitary product composition that exhibits an antiviral effect, or a material or formulation for incorporating them.

[0022] The above antiviral compositions include those used in liquid or gas phase. Antiviral compositions used in liquid phase may contain, in addition to the compounds of the present invention, antimicrobial substances such as hypochlorous acid, hydrogen peroxide, silver ion compounds, cationic antimicrobial agents (such as benzethonium chloride), bactericides (such as triclosan and isopropylmethylphenol), ethanol, surfactants, etc., and are prepared by appropriately blending additives such as chelating agents, humectants, lubricants, builders, buffers, abrasives, electrolytes, bleaches, fragrances, dyes, foaming control agents, corrosion inhibitors, essential oils, thickeners, pigments, gloss enhancers, enzymes, detergents, solvents, dispersants, polymers, silicones, and hydrophobic substances. The form of such compositions may be, but is not limited to, liquid, emulsion, cream, lotion, paste, gel, sheet (supported on a substrate), or oil. This antiviral composition can be appropriately incorporated into various cleaning agents (laundry detergents, household cleaning agents, dishwashing detergents, hair washes, hand washes, body washes, etc.), disinfectants, etc.

[0023] Antiviral compositions used in the gas phase (for example, compositions for deviralizing spaces) may be in liquid or gel form, but are preferably liquid. Such compositions can be prepared by blending the compound of the present invention with a base material and various additives (polyols (dipropylene glycol, propylene glycol, etc.), surfactants, ultraviolet absorbers, antioxidants, preservatives, deodorants, natural extracts, silicones, thickeners, dyes, pigments, colorants, oils, fragrances, etc.). Here, examples of conventionally known base materials, whether oily or aqueous, include water, methanol, ethanol, propanol, isopropanol, butanol, isobutanol, dimethyl ether, liquid propane, petrolatum, lanolin, castor oil, and paraffinic hydrocarbons (for example, liquid paraffin, etc.), which can be used alone or in combination of two or more. Furthermore, when preparing a gel-like formulation, it can be prepared by appropriately adding a natural or synthetic gelling agent, such as a water-soluble gelling agent like carrageenan or gellan gum, or an oil-soluble gelling agent like metal soap or aluminum octylate, according to conventionally known methods.

[0024] Examples of the above-mentioned sanitary product compositions include lotions, creams, shampoos, hair conditioners, hand soaps, body washes, facial cleansers, bath additives, foams, antiperspirants, deodorants, underarm odor preventatives, and oral hygiene products (mouthwash, toothpaste, mouth fresheners, gargles, etc.). The composition can be prepared by conventional methods by appropriately combining carriers that are acceptable as cosmetics, etc. (for example, diluents, dispersants, buffers, pH adjusters, emulsifiers, surfactants, preservatives, stabilizers, antioxidants, colorants, humectants, thickeners, disinfectants, fragrances, etc.).

[0025] The content of the active ingredient in the embodiment in which the virus inactivating agent of the present invention is used as a composition can be appropriately determined depending on the form of the composition. For example, the content of the compound of the present invention 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 still preferably 0.1% by mass or more. Also, it is preferably 99.999% by mass or less, more preferably 50% by mass or less, and still preferably 10% by mass or less. Also, it is preferably 0.001 to 99.999% by mass, more preferably 0.01 to 50% by mass, and still preferably 0.1 to 10% by mass.

[0026] The virus inactivating agent of the present invention makes it possible to inactivate viruses attached to the skin or mucous membranes of animals contaminated with viruses, or to hard or soft surfaces of inanimate objects, as well as to inactivate viruses that have been airborne in living spaces. Examples of surfaces of inanimate objects include hard surfaces such as counters, sinks, powder rooms, toilets, bathtubs, showers, floors, windows, doorknobs, walls, drains, and pipes in homes and business facilities; hard surfaces of various appliances, tools, and miscellaneous goods such as kitchenware, furniture, telephones, and toys; and soft surfaces of textile products such as carpets, area rugs, curtains, fabric furniture, and clothing. Examples of living spaces include general households such as dining kitchens, bedrooms, children's rooms, bathrooms, and toilets; facilities such as shops, restaurants, inns, hospitals, workshops, and factories; vehicles such as automobiles, trains, and aircraft; and semi-enclosed spaces (lockers, storage rooms, closets, etc.).

[0027] In the virus inactivating agent of the present invention, the compound of the present invention or a composition containing the same is applied to an object where viral contamination is a concern, but the embodiment is not particularly limited, and the compound of the present invention may be brought into contact with or reacted with the virus in the gas phase or liquid phase. Methods for bringing the compound of the present invention into contact with the virus in the liquid phase include directly applying the compound of the present invention or a composition containing the same to the object to be treated, diffusing the compound of the present invention or a composition containing the same and sprinkling it on the object to be treated, or wiping the surface of the object with a sheet, gauze, towel, wet wipe, tissue, wet wipe, etc., impregnated with the compound of the present invention or a composition containing the same. Furthermore, by filling the compound of the present invention or a composition containing the same into a container or device for atomization or diffusion, such as a pressurized liquid spray, pressurized air atomizer, diffuser, or nebulizer, and spraying it in a mist-like manner into a space where viruses are present, the volatilization rate can be accelerated, and the virus inactivation effect can be rapidly exerted. Similar effects can also be obtained by using the compound of the present invention or a composition containing the same in the form of an aerosol or mist spray.

[0028] The method for contacting or reacting the compound of the present invention or a composition containing the same with a virus in the gas phase may be either by allowing the compound of the present invention to volatilize naturally or by forcing its volatilization. If the compound of the present invention is allowed to volatilize naturally, viruses present in the space can be inactivated simply by leaving it in a living space, and virus removal (deviral removal) of the space can be easily performed. When the virus inactivator of the present invention is used for the purpose of natural volatilization, conventionally known methods such as impregnating a core rod, filter paper, etc. with the compound of the present invention or a composition containing it and volatilizing it, or volatilizing it using a permeable membrane can be applied. Alternatively, the compound of the present invention or a composition containing it can be kneaded into a resin and used. Examples of resins that can be kneaded include natural, petroleum, and synthetic waxes, rosin resins, ethylene-vinyl acetate copolymers, ethylene-vinyl alcohol copolymers, polyesters, polyolefins, and acrylic resins. The kneaded material can be used as is, or it can be supported on a porous carrier, formed into a sheet, or used as a laminate of the sheet. Examples of porous carriers include natural polymers such as cellulose and chitosan, the synthetic resins mentioned above, and inorganic porous materials such as calcium silicate, all in any shape such as granules or sheets. The kneaded material or laminate can be used by installing it in, for example, air conditioning equipment, toilets, bathrooms, living rooms, hospital rooms, hospital waiting rooms, dustbins, etc., allowing the compound of the present invention to volatilize gradually. Furthermore, the compound of the present invention or a composition containing it can also be used by supporting it on a product made of paper, nonwoven fabric, or the like (such as an air purifier filter). When the compound of the present invention is used by forced volatilization, such means include, for example, a method of volatilization using a fan, a heating volatilization method using a heater, and a method of volatilization using ultrasound.

[0029] When performing airborne virus removal treatment, the amount of the compound of the present invention or a composition containing the same used can be appropriately adjusted depending on the treatment method, the ambient environment such as temperature and humidity, and the vapor pressure of each compound. It is also possible to use a concentration of each compound above its saturation concentration in the space. For example, the concentration of the compound of the present invention in the target space is 0.1% or more, preferably 1% or more, more preferably 5% or more, even more preferably 10% or more, and preferably 10% or less of the saturation concentration of the compound in the space, and is used so that it volatilizes at 100% or less, more preferably 50% or less, and more preferably 25% or less. The concentration of the compound of the present invention in a target space can be detected by measuring the concentration of the compound in a gas sample taken from the space. This can be done using a volatile organic compound concentration meter (VOC meter, odor sensor, etc.), or by using gas chromatography or gas chromatography / mass spectrometry in combination with a gas collection tube.

[0030] With regard to the embodiments described above, the present invention further discloses the following embodiments. <1> A virus inactivator comprising one or more compounds selected from 2-phenylethyl formate, benzyl acetate, methoxycitronellal, cinnamyl alcohol, hydratropic alcohol, dimethylbenzylcarbinol, trans-2-hexen-1-ol, trans-3-hexenol, cis-3-hexenol, and 3-phenylpropionaldehyde as an active ingredient. <2> Use of one or more compounds selected from 2-phenylethyl formate, benzyl acetate, methoxycitronellal, cinnamyl alcohol, hydratropic alcohol, dimethylbenzylcarbinol, trans-2-hexen-1-ol, trans-3-hexenol, cis-3-hexenol, and 3-phenylpropionaldehyde for the production of a virus inactivator. <3> Use of one or more compounds selected from 2-phenylethyl formate, benzyl acetate, methoxycitronellal, cinnamyl alcohol, hydratropic alcohol, dimethylbenzylcarbinol, trans-2-hexen-1-ol, trans-3-hexenol, cis-3-hexenol, and 3-phenylpropionaldehyde, or a composition containing the same, for inactivating viruses. <4> A method for inactivating viruses, comprising applying one or more compounds selected from 2-phenylethyl formate, benzyl acetate, methoxycitronellal, cinnamyl alcohol, hydratropic alcohol, dimethylbenzylcarbinol, trans-2-hexen-1-ol, trans-3-hexenol, cis-3-hexenol, and 3-phenylpropionaldehyde, or a composition containing the same, to an object suspected of viral contamination. <5> <1> ~ <4> In this context, the virus is preferably an enveloped RNA virus. <6> <1> ~ <4> In this context, the virus is preferably an influenza virus or a coronavirus. <7> <1> ~ <6> In this context, virus inactivation is preferably performed in the gas phase. <8> <1> ~ <7> In this case, the content of the compound in the composition containing the compound 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 preferably 99.999% by mass or less, more preferably 50% by mass or less, even more preferably 10% by mass or less, or 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. <9> The compound or a composition containing the same is used such that the concentration of the compound in the target space is 0.1% or more, preferably 1% or more, more preferably 5% or more, even more preferably 10% or more, preferably 100% or less, more preferably 50% or less, and more preferably 25% or less of the saturation concentration of the compound in the space when it volatilizes. <4> The method. [Examples]

[0031] The present invention will be described in more detail below with reference to examples. Example 1: Inactivation of influenza virus in the gas phase using fragrance compounds. 1. Method Influenza virus type A (A / Puerto Rico / 8 / 1934, H1N1) strain was used as the test virus strain. 75 μL of the compounds shown in Table 1 below or mineral oil was soaked into a cotton ball, attached to the lid of a 15 mL glass bottle (Maruemu Co., Ltd.) with double-sided tape, sealed, and left to fill for 30 minutes. 1.5 μL of influenza virus (8.3 × 10⁻⁶) was then added. 5 The FFU was dried on the lid of a cryovial (Thermo Fisher Scientific) for 30 minutes. The lid of the vial, which had the virus attached, was placed in a glass bottle, and the compound and virus were reacted at room temperature (approximately 23°C) for 30 minutes. During this time, the compound was placed on the lid of the bottle and the virus was placed at the bottom of the bottle, maintaining a state where the compound and virus did not come into direct contact. After the reaction, the virus was collected in Hybridoma-SFM medium (Thermo Fisher Scientific) and inoculated into MDCK cells (derived from canine renal tubular epithelial cells) that had been previously cultured in a 12-well plate. After incubation at 37°C under 5% CO2 conditions for approximately 18 hours, the number of foci formed was measured to determine the viral infectivity titer. The infectivity titer when reacted with control mineral oil was set to 100%, and the viral inactivation activity of each compound was calculated. The test was performed three times.

[0032] [Table 1]

[0033] 2.Results As shown in Figure 1, compared to the control mineral oil, compounds 1 to 10 reduced the detectable viral load to 0.001% or less, 0.001% or less, 0.13%, 0.16%, 0.26%, 0.30%, 0.001% or less, 0.001% or less, 0.001% or less, and 0.07%, respectively.

[0034] Example 2: Inactivation of influenza virus in the liquid phase using fragrance compounds 1. Method Influenza virus strain A (A / Puerto Rico / 8 / 1934, H1N1) was used as the test virus strain. The compounds shown in Table 1 were dissolved in Hybridoma-SFM medium (Thermo Fisher Scientific) containing 1% (v / v) dipropylene glycol as a solvent so that the final concentration when reacting with the virus was 0.1% (v / v). The compound solution or the 1% (v / v) dipropylene glycol solution was used to prepare the influenza virus solution (8.3 × 10⁻¹⁰) using the medium as a solvent. 5 60 μL of each FFU was added to a 96-well plate and reacted at room temperature (approximately 23°C) for 30 minutes. After the reaction, the virus was diluted with culture medium and inoculated into MDCK cells (derived from canine renal tubular epithelial cells) that had been previously cultured in a 48-well plate. After incubation at 37°C under 5% CO2 conditions for approximately 18 hours, the number of foci formed was measured to determine the viral infectivity titer. The infectivity titer when reacted with a control 1% (v / v) dipropylene glycol solution was set as 100%, and the viral infectivity titer of each compound was calculated. The test was performed three times.

[0035] 2.Results As shown in Figure 2, compared to the control 1% dipropylene glycol solution, compounds 1-10 reduced the detectable viral load to 68.9%, 71.5%, 65.6%, 67.1%, 68.0%, 59.7%, 67.1%, 79.5%, 80.3%, and 57.2%, respectively.

Claims

1. A virus inactivating agent used to inactivate a virus in the gas phase, comprising one or more compounds selected from 2-phenylethyl formate, methoxycitronellal, hydratropic alcohol, and dimethylbenzylcarbinol as an active ingredient, wherein the virus is an enveloped RNA virus.

2. The virus inactivator according to claim 1, wherein the virus is an influenza virus or a coronavirus.

3. A method for inactivating a virus, comprising contacting or reacting a virus in the gas phase with one or more compounds selected from 2-phenylethyl formate, methoxycitronellal, hydratropic alcohol, and dimethylbenzylcarbinol, or a composition containing the same, wherein the virus is an enveloped RNA virus.

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