JP2023063147A - virus inactivator - Google Patents

Abstract

To provide a virus inactivator that can inactivate virus in a space.SOLUTION: A virus inactivator comprises at least one compound selected from benzyl alcohol, phenylethyl alcohol, isoamyl alcohol, amyl alcohol, octanal, hexanol, hexanoic acid, heptanol, octanol, nonanol, decanol, 1-dodecanol and dodecanal as an active ingredient and inactivates virus in a vapor phase.SELECTED DRAWING: None

Description

TECHNICAL FIELD The present invention relates to a virus inactivating agent that inactivates viruses existing in space.

Viral infections are diseases that cause severe symptoms such as cold symptoms, pneumonia, hepatitis, encephalitis, and the like, and are an everlasting threat to mankind. In recent years, influenza viruses have raged all over the world, and in some cases, outbreaks of new strains of influenza with altered antigenicity have caused pandemics. In 2019, SARS coronavirus-2 (SARS-CoV-2) emerged and caused a pandemic, affecting not only life and health but also economic activities and social functions.

Vaccines and antiviral agents have been developed to deal with such situations, but the development of vaccines and therapeutic agents takes time and is not necessarily successful.
When the virus is brought into the living space by an infected person, the infection spreads directly from the patient or through the environment including clothing, various instruments/members, walls and equipment such as air conditioners. Therefore, it is recommended to remove viruses and inactivate viruses by washing and disinfecting hands, clothes, various instruments and parts that viruses can attach to, and inactivating viruses that are splashed in living spaces and viruses that are floating in the air as aerosols. It is considered effective to prevent the spread of infection.

Conventionally, ethanol, sodium hypochlorite, chlorine dioxide, glutaraldehyde, etc. have been used for the purpose of inactivating viruses. However, these general antiseptics are highly irritating to mucous membranes and skin, and their use is limited due to safety concerns. Spraying chlorine dioxide has also been devised as a method of chemically inactivating viruses in space, but its effectiveness is uncertain.

Some alcohols, aldehydes, and carboxylic acids are known to have virus-inactivating effects in liquid-phase evaluations. For example, hexanol is known to have an inactivating effect on vesicular stomatitis virus, and phenylethyl alcohol has an inactivating effect on enveloped virus at -20°C (Patent Document 1, Non-Patent Document 1). It has also been reported that octanal and dodecanal inactivate herpes simplex virus type 1, and hexanoic acid inactivates hepatitis C virus (Non-Patent Documents 2 and 3).

However, those that are active in these liquid-phase evaluations exhibit virus-inactivating effects when mixed with viruses in liquids, but exhibit virus-inactivating effects when diffused in space as volatile compounds. It is not clear whether or not, or to what extent the virus inactivation effect is exhibited.

U.S. Pat. No. 4,909,940

Roihel et al., Acta Virol. 1969;13(2):139-141 Hayashi K, et al., Planta Med. 1995;61(3):237-241 Pfaender et al., J Infect Dis. 2013;208(12):1943-1952

The present invention relates to providing a virus-inactivating agent capable of inactivating viruses existing in space.

The present inventors have found that a specific volatile compound has an effect of inactivating influenza virus in the gas phase and is useful as a virus inactivating agent.

That is, the present invention relates to the following 1) and 2).
1) One or more compounds selected from benzyl alcohol, phenylethyl alcohol, isoamyl alcohol, amyl alcohol, octanal, hexanol, hexanoic acid, heptanol, octanol, nonanol, decanol, 1-dodecanol and dodecanal are used as active ingredients in a gas phase A virus-inactivating agent that inactivates viruses in
2) One or more compounds selected from benzyl alcohol, phenylethyl alcohol, isoamyl alcohol, amyl alcohol, octanal, hexanol, hexanoic acid, heptanol, octanol, nonanol, decanol, 1-dodecanol and dodecanal, or a composition containing the same A virus inactivation method in which the virus is contacted or reacted in the gas phase.

According to the virus inactivating agent of the present invention, viruses adhering to hard and soft surfaces in the living environment, viruses splashed in the living space, and viruses drifting in the space as aerosols can be inactivated, and the spread of infection by the virus can be inactivated. can be prevented or reduced.

Influenza virus inactivation effect (gas phase). Influenza virus inactivation effect (liquid phase).

Benzyl alcohol, phenylethyl alcohol, isoamyl alcohol, amyl alcohol, octanal, hexanol, hexanoic acid, heptanol, octanol, nonanol, decanol, 1-dodecanol and dodecanal of the present invention (hereinafter also referred to as "the compound of the present invention") is also a compound used as a fragrance, and is commercially available as follows.
Benzyl alcohol (alias: phenylmethanol): Tokyo Chemical Industry Co., Ltd. Phenylethyl alcohol (alias: 2-phenylethanol): Sigma-Aldrich, Tokyo Chemical Industry Co., Ltd. Isoamyl alcohol (alias: 3-methyl-1-butanol) : Tokyo Chemical Industry Co., Ltd., Sigma-Aldrich Co. Amyl alcohol (also known as 1-pentanol): Tokyo Chemical Industry Co., Ltd., Sigma-Aldrich Co.
・Octanal (alias: caprolic aldehyde): Sigma-Aldrich, Tokyo Chemical Industry ・Hexanol (alias: 1-hexanol): Tokyo Chemical Industry, Sigma-Aldrich ・Hexanoic acid (alias: caproic acid): Tokyo Chemical Industry Company, Fujifilm Wako Pure Chemical Co., Ltd. ・Heptanol (alias: 1-heptanol): Tokyo Chemical Industry Co., Ltd., Sigma-Aldrich ・Octanol (alias: 1-octanol): Tokyo Chemical Industry Co., Ltd., Sigma-Aldrich ・Nonanol (alias : 1-nonanol): Tokyo Chemical Industry Co., Ltd., Sigma-Aldrich ・Decanol (alias: 1-decanol): Sigma-Aldrich Co., Tokyo Chemical Industry Co., Ltd. ・1-dodecanol (alias: lauryl alcohol): Tokyo Chemical Industry Co., Ltd., Sigma-Aldrich Co. ・Dodecanal (also known as lauryl aldehyde): Sigma-Aldrich Co., Fujifilm Wako Pure Chemical Co., Ltd.

Such compounds may be used alone or in combination of two or more.

Among the compounds of the present invention, benzyl alcohol, isoamyl alcohol, amyl alcohol, octanal, hexanol, phenylethyl alcohol, hexanoic acid, heptanol, odor intensity and quality, and volatility are preferable from the viewpoint of virus inactivation effect. benzyl alcohol, phenylethyl alcohol, and comprehensively benzyl alcohol, phenylethyl alcohol, isoamyl alcohol, amyl alcohol and octanal.
In the present invention, such compounds are used in the gas phase.

Viruses to which the virus inactivating agent of the present invention is applied include all types of viruses, regardless of the types of nucleic acids (RNA, DNA) and the presence or absence of envelopes.
SARS coronavirus; SARS coronavirus-2; respiratory syncytial virus; mumps virus; Lassa virus; dengue virus; human herpes virus; vaccinia virus; hepatitis B virus, etc., having DNA.
In addition, non-enveloped viruses include norovirus, poliovirus, echovirus, hepatitis A virus, hepatitis E virus, rhinovirus, astrovirus, rotavirus, coxsackievirus, enterovirus, and sapovirus. , adenovirus, which has DNA as the nucleic acid; B19 virus; papovavirus; human papillomavirus, and the like.

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

In the present invention, virus inactivation means the action of reducing or eliminating virus activity and eliminating the ability to infect host cells.
The virus-inactivating action can be confirmed by, for example, contacting the test article with the virus, infecting the host cell with the virus, and measuring the virus infectivity. Here, the host cell may be any cell in which the target virus can proliferate. In the case of influenza virus, for example, canine kidney cells (MDCK), African green monkey kidney epithelial cells (Vero), duck embryonic stem cell-derived cells. Cell line (EB66), human coronavirus, human ileocecal adenocarcinoma cell line (HCT-8), African green monkey kidney epithelial cell line (VeroE6), human liver cancer-derived cell line line (Huh7) can be done.

As shown in the examples below, the compound of the present invention impregnated into a cotton ball is placed in a glass bottle and filled with the dried influenza virus. , the viral infectious titer is reduced by more than 13%.
Therefore, the compounds of the present invention can be virus-inactivating agents that inactivate viruses in the gas phase. Alternatively, the compounds of the invention can be used to produce virus-inactivating agents that inactivate viruses in the gas phase.
The compounds of the invention can also be used to inactivate viruses in the gas phase.

The virus inactivating agent of the present invention may be in the form of using the compound of the present invention alone, or may be in the form of a composition containing it. That is, the virus inactivating agent of the present invention becomes an antiviral composition that exhibits a virus inactivating effect in the gas phase, more specifically, a composition for removing viruses in space, or a material or formulation for blending into these. obtain.
Spaces include dining kitchen rooms, bedrooms, children's rooms, bathrooms, toilets, and other general household facilities; shops, restaurants, inns, hospitals, workshops, factories, and other facilities; automobiles, trains, aircraft, and other vehicles. Among them, living spaces such as semi-closed spaces (lockers, storerooms, closets, etc.) can be mentioned.

The form of the antiviral composition includes a liquid form, a gel form, and the like, and a liquid form is preferred. In addition to the compound of the present invention, the composition contains a base material and various additives (polyols (dipropylene glycol, propylene glycol, etc.), surfactants, ultraviolet absorbers, antioxidants, preservatives, deodorants, natural extracts, silicones, thickeners, dyes, pigments, pigments, oils, perfumes, etc.). Here, as the base, water, methanol, ethanol, propanol, isopropanol, butanol, isobutanol, dimethyl ether, liquid propane, petrolatum, lanolin, castor oil, paraffinic hydrocarbons (for example, , liquid paraffin, etc.), which can be used alone or in combination of two or more.
In the case of preparing a gel formulation, for example, a natural gelling agent or a synthetic gelling agent such as a water-soluble gelling agent such as carrageenan and gellan gum, a metal soap, an oil-soluble gelling agent such as aluminum octylate, etc. is conventionally used. It may be added as appropriate according to a known method.

The content of the active ingredient in the aspect of using the virus inactivating agent of the present invention as a composition can be appropriately determined according to 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 even more preferably 0.1% by mass or more. Moreover, it is preferably 99.999% by mass or less, more preferably 50% by mass or less, and even more 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, even more preferably 0.1 to 10% by mass.

In the virus inactivating agent of the present invention, the compound of the present invention or a composition containing the same is applied to a subject that is concerned about viral contamination. The compound of the present invention may be brought into contact with or reacted with a virus, and the compound of the present invention may be spontaneously volatilized or forced to volatilize.
If the compound of the present invention is in a form that naturally volatilizes, viruses existing in the space can be inactivated simply by leaving it in the living space, and viruses in the space can be easily removed (virus removal).
When the virus inactivating agent of the present invention is used for the purpose of natural volatilization, for example, the compound of the present invention or a composition containing the same is soaked into a core rod, filter paper, etc. to volatilize, or using a permeable membrane. A conventionally known method such as a volatilization method can be applied. Alternatively, the compound of the present invention or a composition containing the same may be kneaded with a resin for use. 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 above kneaded product can be used as it is, or can be supported on a porous carrier, formed into a sheet, or formed into a laminate from the sheet. Examples of porous carriers include natural polymers such as cellulose and chitosan, synthetic resins described above, inorganic porous substances such as calcium silicate, and the like, which are formed into arbitrary shapes such as granules and sheets. The above-mentioned kneaded product or laminate can be used, for example, by installing it in air conditioning equipment, toilets, bathrooms, living rooms, hospital rooms, hospital waiting rooms, dust boxes, etc., and gradually volatilizing the compound of the present invention. In addition, the compound of the present invention or a composition containing it can also be used by supporting it on a product made of paper, non-woven fabric, etc. (air purifier filter, etc.).

When the compound of the present invention is forcibly volatilized and used, such means include, for example, a method of volatilizing using a fan or the like, a method of volatilizing by heating using a heater or the like, a method of volatilizing by ultrasonic waves, and the like.

In addition, the compound of the present invention or a composition containing it is filled into a container or device for atomization or diffusion, such as a pressurized liquid atomizer, a pressurized air atomizer, a diffuser, a nebulizer, etc. By spraying it in the space where the virus exists in the form of a mist, the volatilization rate can be increased, and the virus inactivation effect can be rapidly exhibited. Similar effects can also be obtained by using the compound of the present invention or a composition containing it in the form of an aerosol, mist spray, or the like.

In the case of spatial virus removal treatment, the amount of the compound of the present invention or the composition containing it can be appropriately adjusted depending on the mode of treatment, the spatial environment such as temperature and humidity, the vapor pressure of each compound, etc. The concentration of the compound of the present invention in the space can be higher than the saturation concentration of the compound, but for example, the concentration of the compound of the present invention in the target space is 0.1% or more, preferably 1% or more of the saturation concentration of the compound in the space. It is preferably 5% or more, more preferably 10% or more, preferably 100% or less, more preferably 50% or less, and more preferably 25% or less.
The concentration of the compound of the present invention in the target space can be detected by measuring the concentration of the compound in the gas sampled from the space. Examples thereof include a method of determination using gas chromatography or gas chromatography/mass spectrometry in combination with a collection tube or the like.

The following aspects are further disclosed in this invention regarding embodiment mentioned above.
<1> One or more compounds selected from benzyl alcohol, phenylethyl alcohol, isoamyl alcohol, amyl alcohol, octanal, hexanol, hexanoic acid, heptanol, octanol, nonanol, decanol, 1-dodecanol and dodecanal as an active ingredient, A virus-inactivating agent that inactivates viruses in phase.
<2> Use of one or more compounds selected from <2> for producing a virus-inactivating agent that inactivates viruses in the gas phase.
<3> 1 selected from benzyl alcohol, phenylethyl alcohol, isoamyl alcohol, amyl alcohol, octanal, hexanol, hexanoic acid, heptanol, octanol, nonanol, decanol, 1-dodecanol and dodecanal for inactivating viruses in the gas phase Use of more than one species of compound.
<4> One or more compounds selected from benzyl alcohol, phenylethyl alcohol, isoamyl alcohol, amyl alcohol, octanal, hexanol, hexanoic acid, heptanol, octanol, nonanol, decanol, 1-dodecanol and dodecanal, or a composition containing the same A virus inactivation method in which substances are brought into contact with or react with viruses in the gas phase.
<5> In <1> to <4>, the virus is preferably an enveloped RNA virus.
<6> In <1> to <4>, the virus is preferably influenza virus or coronavirus.
<7> In <1> to <6>, the content of the compound with respect to the total amount of the composition in the composition containing the compound is preferably 0.001% by mass or more, more preferably 0.01% by mass. % or more, more preferably 0.1 mass % or more, and preferably 99.999 mass % or less, more preferably 50 mass % or less, still more preferably 10 mass % or less, or preferably 0.001 mass % ~99.999% by mass, more preferably 0.01 to 50% by mass, still more preferably 0.1 to 10% by mass.
<8> the compound or the composition containing the same, wherein the concentration of the compound in the target space is 0.1% or more, preferably 1% or more, more preferably 5% or more of the saturation concentration of the compound in the space; The method of <4> is more preferably 10% or more, preferably 100% or less, more preferably 50% or less, and more preferably 25% or less.

EXAMPLES Hereinafter, the present invention will be described more specifically by showing examples.
Example 1 Inactivation of Influenza Virus in Vapor Phase by Fragrance Compounds 1 . Methods Influenza virus type A (A/Puerto Rico/8/1934, H1N1) strain was used as the test virus strain. A cotton ball was impregnated with 75 μL of the compound shown in Table 1 below or mineral oil, and the cap of a 15 mL glass bottle (Maruem Co., Ltd.) was sealed with double-sided tape and filled for 30 minutes. 1.5 μL (8.3×10 ⁵ FFU) of influenza virus was allowed to dry on the lid of a cryovial (Thermo Fisher Scientific) for 30 minutes. The virus-attached vial lid was placed in a glass bottle, and the compound was allowed to react with the virus at room temperature (approximately 23° C.) for 30 minutes. At that time, the compound was placed on the lid of the bottle, and the virus was placed on the bottom of the bottle, so that the compound and the virus did not come into direct contact with each other. After the reaction, the virus was recovered with Hybridoma-SFM medium (Thermo Fisher Scientific), inoculated into MDCK cells (derived from canine kidney tubular epithelial cells) previously cultured in a 12-well plate, and placed at 37°C in 5% CO. After culturing for about 18 hours under _{the two} conditions, the number of foci formed was measured, and the virus infection titer was determined. The virus-inactivating activity of each compound was calculated based on the infectious titer when reacted with the control mineral oil as 100%. The test was performed 3 times.

2. Results As shown in FIG. 1, compounds 1-13 reduced the detectable viral load to 0.001% or less, 0.04%, 0.001% or less, 0.001% or less, respectively, compared to the control mineral oil. 0.01%, 0.01%, 0.13%, 0.67%, 23.7%, 44.7%, 65.5%, 67.3% and 86.6%.

Reference Example Inactivation of Influenza Virus in Liquid Phase by Perfume Compound 1. Methods Influenza virus type A (A/Puerto Rico/8/1934, H1N1) strain was used as the test virus strain. Hybridoma-SFM medium (Thermo Fisher Scientific). Compound solution or 1% (v/v) dipropylene glycol solution and influenza virus solution (8.3 × 10 ⁵ FFU) using medium as solvent (60 µL each) were added to a 96-well plate and incubated at room temperature (approximately 23°C). React for 30 minutes. After the reaction, the virus was diluted with a medium, inoculated into MDCK cells (derived from canine renal tubular epithelial cells) previously cultured in a 48-well plate, and cultured at 37°C, 5% _CO2 for about 18 hours. The number of foci formed was measured and the virus infection titer was determined. The virus infection titer of each compound was calculated by setting the infection titer when reacted with the control 1% (v/v) dipropylene glycol solution as 100%. The test was performed 3 times.

2. Results As shown in Figure 2, compared to the control 1% dipropylene glycol solution, compounds 1-9 reduced the amount of virus detected by 76.2%, 84.1%, 69.9%, 73.0%, respectively. 67.0%, 81.5%, 82.0%, 65.3%, 73.4%, 76.9%, 20.6%, 21.1% and 33.8%.

Claims (4)

One or more compounds selected from benzyl alcohol, phenylethyl alcohol, isoamyl alcohol, amyl alcohol, octanal, hexanol, hexanoic acid, heptanol, octanol, nonanol, decanol, 1-dodecanol and dodecanal are used as active ingredients, and the virus in the gas phase A virus inactivating agent that inactivates The virus-inactivating agent according to claim 1, wherein the virus is an enveloped RNA virus. 3. The virus inactivating agent according to claim 1 or 2, wherein the virus is influenza virus or coronavirus. One or more compounds selected from benzyl alcohol, phenylethyl alcohol, isoamyl alcohol, amyl alcohol, octanal, hexanol, hexanoic acid, heptanol, octanol, nonanol, decanol, 1-dodecanol and dodecanal, or a composition containing the same A virus inactivation method in which the virus is contacted or reacted in phase.

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