Virus inactivation composition for liquid atomization
Patent Information
- Application Number
- JP2022067238
- Authority / Receiving Office
- JP · JP
- Patent Type
- Applications
- Current Assignee / Owner
- Priority Date
- 2022-02-09
- Filing Date
- 2022-04-14
- Publication Date
- 2025-04-01
- Estimated Expiration
- Not applicable · inactive patent
AI Technical Summary
Existing antiviral agents for spraying, such as ethanol and chlorine dioxide, are limited due to safety concerns and irritation, and diols with boiling points below 220°C and 2-4 carbon atoms are viscous and cannot be effectively sprayed for virus inactivation.
A composition comprising 40-90% diol with 2-4 carbon atoms and 10-60% water, optionally with glycol ethers and alkyl glyceryl ethers, is formulated for spraying, providing a safe and effective method to inactivate viruses on surfaces and in the air.
The composition effectively inactivates viruses on surfaces and in the air, reducing the spread of infection by ensuring broad-spectrum virus inactivation, including enveloped and non-enveloped viruses, with minimal irritation and safety risks.
Abstract
Description
[Technical Field]
[0001] The present invention relates to a virus inactivation composition for liquid spraying and a virus inactivation method. [Background technology]
[0002] Viral infections are diseases that cause serious symptoms ranging from the common cold to pneumonia, hepatitis, and encephalitis, and remain a perpetual threat to humanity. In recent years, influenza viruses have raged globally, and sometimes pandemics have occurred due to the emergence of novel influenza strains with altered antigenicity. Furthermore, in 2019, SARS coronavirus-2 (SARS-CoV-2) emerged, causing a pandemic that affected not only life and health but also economic activity and social functions.
[0003] Viruses spread through contact transmission via hands and various tools and materials, droplet transmission through direct inhalation of droplets generated by coughing, sneezing, or talking, and airborne transmission through inhalation of airborne droplets. Therefore, it is considered effective in preventing the spread of infection by removing or inactivating viruses by washing and disinfecting objects to which viruses may adhere, and by inactivating viruses that are airborne or have become airborne in the space. [Prior art documents] [Patent Documents]
[0004] [Patent Document 1] Special Publication No. 4-502616 [Overview of the Initiative]
[0005] Traditionally, ethanol, sodium hypochlorite, chlorine dioxide, and glutaraldehyde have been used to inactivate viruses. However, these agents are highly irritating to mucous membranes and skin, limiting their use due to safety concerns and allergy issues. They are particularly unsuitable for use in inactivating viruses using sprayers. For example, disinfection of workspaces in vehicles such as automobiles (garbage trucks, buses, etc.), trains, and aircraft by spraying ethanol is limited due to the risk of ignition. Furthermore, spraying chlorine dioxide has been considered as a method to chemically inactivate viruses present in the air, but its effectiveness is not yet certain.
[0006] Diols with a boiling point of 220°C or lower and having 2 to 4 carbon atoms are a type of polyhydric alcohol used in solvents, antifreeze, lubricants, pharmaceuticals, etc. For example, Patent Document 1 discloses a virucidal liquid composition containing glutaraldehyde and approximately 10 to 20% by weight of a glycol such as propylene glycol to reduce its odor. As described in Patent Document 1, diols with a boiling point of 220°C or lower and having 2 to 4 carbon atoms, such as propylene glycol, have been reported to have an inactivating effect on influenza viruses and the like. However, since diols with a boiling point below 220°C and 2 to 4 carbon atoms are viscous liquids, they cannot be sprayed to inactivate viruses. To date, no antiviral sprays utilizing the virus-inactivating properties of diols with a boiling point below 220°C and 2 to 4 carbon atoms are known. [Problems that the invention aims to solve]
[0007] The present invention relates to providing a virus inactivation composition for liquid spraying and a virus inactivation method that enable the inactivation of viruses present in the environment. [Means for solving the problem]
[0008] The inventors have discovered that any composition containing a diol with 2 to 4 carbon atoms and water at specific concentrations, with a boiling point of 220°C or lower, can be sprayed, and that the diol with 2 to 4 carbon atoms and a boiling point of 220°C or lower exhibits a virus inactivation effect. Furthermore, they have found that alkyl glyceryl ethers and specific fragrances have a virus inactivation effect, and that combining these with a diol with 2 to 4 carbon atoms and a boiling point of 220°C or lower improves the virus inactivation effect.
[0009] In other words, the present invention relates to the following 1) to 3). 1) A virus inactivation composition for liquid spraying, wherein A1) a composition containing 40-90% by mass of a diol having 2-4 carbon atoms and a boiling point of 220°C or less, and 10-60% by mass of water. 2) A1) A method for inactivating viruses, comprising spraying a composition containing 40-90% by mass of a diol having 2-4 carbon atoms and a boiling point of 220°C or lower, and 10-60% by mass of water, onto the hard or soft surface of an inanimate object suspected of viral contamination, or onto waste. 3) A method for inactivating viruses in a target space, comprising spraying a composition containing 40-90% by mass of a diol having 2-4 carbon atoms and a boiling point of 220°C or lower, and 10-60% by mass of water, onto a carrier, and vaporizing the composition from the carrier so that the concentration of the diol having 2-4 carbon atoms and a boiling point of 220°C or lower in the space is 20 ppm or higher. [Effects of the Invention]
[0010] According to the present invention, viruses attached to objects in the living environment and viruses in the air can be inactivated, thereby preventing or reducing the spread of infection caused by such viruses. [Modes for carrying out the invention]
[0011] The virus inactivation composition for liquid spraying of the present invention (hereinafter also referred to as "the composition") contains A1) a diol having a boiling point of 220°C or less and having 2 to 4 carbon atoms. Furthermore, it is preferable that the composition of the present invention uses a diol having a boiling point of 220°C or less and having 2 to 4 carbon atoms as the active ingredient for virus inactivation. In the present invention, the boiling point means the initial boiling point at 1 atm or the temperature range in the boiling state. When the boiling point is 220°C or lower, examples of the diol having 2 to 4 carbon atoms include ethylene glycol (boiling point 197°C), 1,2-propanediol (boiling point 188°C), 1,3-propanediol (boiling point 213°C), 1,2-butanediol (boiling point 192°C), 1,3-butanediol (boiling point 207°C), and 2,3-butanediol (boiling point 177°C). Among these, from the viewpoint of easy vaporization after liquid spraying, 1,2-propanediol (boiling point 188°C), 2,3-butanediol (boiling point 177°C), 1,2-butanediol (boiling point 192°C), and ethylene glycol (boiling point 197°C) are preferable, and from the viewpoint of less odor, 1,2-propanediol (boiling point 188°C) is more preferable.
[0012] The composition of the present invention preferably contains, in addition to the above A1) diol having 2 to 4 carbon atoms with a boiling point of 220°C or lower, A2) glycol ether having 6 carbon atoms with a boiling point of 220°C or lower. The content of A2) in the composition is 50% by mass or less, and the total amount of A1) and A2) exceeds 40% by mass and is 90% by mass or less. Examples of the glycol ether having 6 carbon atoms with a boiling point of 220°C or lower include diethylene glycol monoethyl ether (also known as ethyl carbitol, ethyl diglycol, boiling point 202°C), ethylene glycol monobutyl ether (also known as butyl cellosolve, boiling point 171°C). Among them, diethylene glycol monoethyl ether is preferable from the viewpoint of less odor.
[0013] In the composition, A2) has a boiling point of 220°C or lower, and the content of the glycol ether having 6 carbon atoms is preferably 1% by mass or more, more preferably 3% by mass or more, and still more preferably 7% by mass or more from the viewpoints of reducing the viscosity of the composition and facilitating spraying, and solubilizing the fragrance when the composition contains a fragrance, and enhancing the fragrance indicator property and antiviral effect by the fragrance. Also, from the viewpoint of reducing the base damage of the object to be sprayed, it is preferably 40% by mass or less, more preferably 30% by mass or less, still more preferably 20% by mass or less, still more preferably 15% by mass or less, and still more preferably 10% by mass or less. In the present invention, the fragrance indicator property means that as an indicator of whether it has been sprayed or not, the fragrance is easy to recognize and its disappearance is easy to understand.
[0014] In the composition, the mass ratio [A2) / (A1)+A2)] of A2) the glycol ether having 6 carbon atoms with a boiling point of 220°C or lower to the total amount of A1) the diol having 2 to 4 carbon atoms and A2) the glycol ether having 6 carbon atoms with a boiling point of 220°C or lower is preferably 0.05 or more, more preferably 0.1 or more, and still more preferably 0.15 or more from the viewpoints of reducing the viscosity of the composition and facilitating spraying, and solubilizing the fragrance when the composition contains a fragrance, and enhancing the fragrance indicator property and antiviral effect by the fragrance. Also, from the viewpoint of reducing the base damage of the object to be sprayed, it is preferably 1.0 or less, more preferably 0.5 or less, and still more preferably 0.3 or less.
[0015] From the viewpoints of reducing viscosity and virus inactivation, the composition of the present invention preferably further contains A3) alkyl glyceryl ether. Examples of alkylglyceryl ethers include alkylglyceryl ethers having one alkyl group with 8 to 18 carbon atoms, preferably 8 to 14 carbon atoms, more preferably 8 to 12 carbon atoms, and even more preferably 8 to 10 carbon atoms. Examples of alkyl groups include linear alkyl groups and branched alkyl groups, with branched alkyl groups being preferred, a 2-ethylhexyl group, an isononyl group, or an isodecyl group being more preferred, and a 2-ethylhexyl group being even more preferred. Among these, alkylglyceryl ethers having one branched alkyl group with 8 to 12 carbon atoms are preferred, alkylglyceryl ethers having one branched alkyl group with 8 carbon atoms are more preferred, and 2-ethylhexylglyceryl ether is even more preferred.
[0016] The content of A3) alkylglyceryl ether in the composition is preferably 0.1% by mass or more, more preferably 0.2% by mass or more, and even more preferably 0.4% by mass or more, from the viewpoint of reducing viscosity and inactivating viruses, and from the viewpoint of reducing irritation when the spray comes into contact with the human body, it is preferably 2% by mass or less, more preferably 1% by mass or less, even more preferably 0.9% by mass or less, and even more preferably 0.8% by mass or less. The mass ratio of A3) alkyl glyceryl ether to A1) diol having a boiling point of 220°C or lower and having 2 to 4 carbon atoms [A3) / A1)] in the composition is preferably 0.001 or higher, more preferably 0.005 or higher, and even more preferably 0.01 or higher, from the viewpoint of reducing viscosity, and from the viewpoint of reducing irritation when the spray comes into contact with the human body, it is preferably 0.1 or lower, more preferably 0.05 or lower, even more preferably 0.04 or lower, and even more preferably 0.03 or lower.
[0017] The composition of the present invention preferably further contains a fragrance (excluding diols with a boiling point of 220°C or lower and 2 to 4 carbon atoms) as a fragrance indicator to determine whether or not it has been sprayed. A fragrance indicator is a fragrance that can be perceived when sprayed but does not linger for a long time, and serves as an indicator of whether or not it has been sprayed on an object. From the viewpoint of indicator properties, the boiling point of the fragrance is preferably 120°C to 260°C, more preferably 130°C to 220°C, and more preferably 140°C to 220°C. In this invention, the indicator properties of a fragrance refer to the fact that the fragrance is easily recognizable and its disappearance is easily discernible. Examples of fragrances include hydrocarbons, aldehydes, ketones, alcohols, phenols, lactones, esters, ethers, and thiols. Among these, monoterpene hydrocarbons, aldehydes, alcohols, and esters are preferred from the viewpoint of having a desirable fragrance quality and a large number of compounds with low thresholds. These can be used individually or in combination of two or more. Compounds with a low threshold are preferred here because their scent can be perceived even in small amounts.
[0018] Suitable monoterpene hydrocarbons include, for example, limonene (boiling point 177°C). Limonene can be used in the form of essential oils rich in limonene, such as lemon oil, orange oil, grapefruit oil, bergamot oil, and yuzu oil.
[0019] Suitable aldehydes, alcohols, and esters include compounds represented by the following general formula (I).
[0020] [ka]
[0021] (In the formula, R 1 represents a hydrocarbon group having 4 to 10 carbon atoms, which may have substituents; A represents a hydroxyl group or has one of the following structures: (a) or (b);
[0022] [ka]
[0023] R 2 (This represents a hydrogen atom or an alkyl group having 1 to 3 carbon atoms.)
[0024] In general formula (I), R 1 Examples of hydrocarbon groups having 4 to 10 carbon atoms represented by include aliphatic hydrocarbon groups and aromatic hydrocarbon groups. Aliphatic hydrocarbon groups may be linear, branched, or cyclic, and may be saturated or unsaturated. Examples of saturated aliphatic hydrocarbon groups include linear, branched, or cyclic saturated aliphatic hydrocarbon groups, such as alkyl groups including n-butyl, isobutyl, sec-butyl, tert-butyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, pentyl, hexyl, heptyl, octyl, nonyl, and decyl groups; and cycloalkyl groups such as cyclobutyl, cyclopentyl, cyclohexyl, 2-isopropyl-5-methylcyclohexyl (menthyl), cycloheptyl, cyclooctyl, cyclononyl, and cyclodecyl groups. Unsaturated aliphatic hydrocarbon groups include linear, branched, or cyclic unsaturated aliphatic hydrocarbon groups having one or more double bonds in the molecule, such as alkenyl groups like n-butenyl, isobutenyl, pentenyl, hexenyl, heptenyl, octenyl, 3,7-dimethyl-6-octenyl, nonenyl, and decenyl; and cyclobutenyl, cyclopentenyl, and cyclohexenyl groups. Examples include cycloalkenyl groups such as cenyl group and 1-isopropyl-4-methyl-3-cyclohexenyl group; and alkadienyl groups such as butanedienyl group, pentadienyl group, hexadienyl group, heptadienyl group, octadienyl group, nonadienyl group, decanedienyl group, 1,5-dimethyl-1-vinyl-4-hexenyl group, and 3,7-dimethyl-2,6-octadienyl group (geranyl group). Examples of aromatic hydrocarbon groups include aryl groups such as phenyl groups; aralkyl groups such as benzyl and phenethyl groups; and styryl and cinnamyl groups.
[0025] The groups that can be substituted for the C4-C10 hydrocarbon group are preferably C1-C3 alkoxy groups. C1-C3 alkoxy groups are linear or branched alkoxy groups with C1-C3, and include methoxy groups, ethoxy groups, n-propoxy groups, isopropoxy groups, and the like.
[0026] In general formula (I), R 2 The C1-C3 alkyl group represented by represents a linear, branched, or cyclic alkyl group having 1-C3 carbon atoms, and examples include a methyl group, an ethyl group, an n-propyl group, an isopropyl group, and a cyclopropyl group.
[0027] From the viewpoint of virus inactivation and the abundance of low-threshold compounds, the preferred fragrances of the present invention are, in general formula (I), R 1 is an alkyl or alkenyl group having 4 to 10 carbon atoms; A represents a hydroxyl group or has either structure (a) or (b) above; R 2 It is a compound in which the atom is either a hydrogen atom or a methyl group.
[0028] From the viewpoint of fragrance indicator properties, more preferred fragrances of the present invention are the following fragrances having a boiling point in the range of 120°C to 260°C. Examples of fragrances with a boiling point of 120°C to 130°C: Examples include isoamyl formate (boiling point 123°C), butyl acetate (boiling point 126°C), and cis-3-hexenal (boiling point 126°C). Examples of fragrances with a boiling point above 130°C to 140°C: Examples include 3-methyl-1-butanol (isoamyl alcohol, boiling point 132°C), 1-pentanol (n-amyl alcohol, boiling point 138°C), etc. Examples of fragrances with boiling points above 140°C to 180°C: Isoamyl acetate (boiling point 142°C), trans-2-hexenal (boiling point 146°C), cis-3-hexenyl formate (boiling point 155°C), hexyl formate (boiling point 155°C), trans-3-hexenol (boiling point 155°C), cis-3-hexenol (boiling point 156°C), hexyl alcohol (boiling point 156°C), trans-2-hexenol (boiling point 159°C), trimethylhexanal (3,5,5-trimethyl Examples include methylhexanal (boiling point 167°C), cis-3-hexenyl acetate (boiling point 169°C), dimitol (registered trademark, 2,4-dimethyl-2-heptanol, boiling point 170°C), hexyl acetate (boiling point 172°C), 3-methyl-3-methoxybutanol (boiling point 174°C), heptyl alcohol (boiling point 175°C), limonene (boiling point 177°C), isoamyl butyrate (boiling point 178°C), benzaldehyde (boiling point 178°C), etc. Examples of fragrances with a boiling point between 180°C and 220°C: Melonal (2,6-dimethyl-5-heptenal, boiling point 188°C), Cyclobertal (registered trademark, 3,6-dimethylcyclohexe-3-ene-1-carboaldehyde, boiling point 189°C), Trimethylhexanol (3,5,5-trimethylhexanol, boiling point 193°C), Dihydromyrcenol (boiling point 194°C), Linalool (boiling point 199°C), Linalyl formate (boiling point 202°C) Examples include benzyl alcohol (boiling point 205°C), benzyl acetate (boiling point 212°C), dimethylbenzylcarbinol (2-methyl-1-phenylpropan-2-ol, boiling point 215°C), geranyl formate (boiling point 216°C), phenylethyl alcohol (boiling point 219°C), linalyl acetate (boiling point 220°C), hydratropic alcohol (2-phenylpropanol, boiling point 220°C), etc. Examples of fragrances with a boiling point between 220°C and 260°C: Syringaldehyde (2-(4-(methylphenyl)acetaldehyde) (boiling point 221°C), phenylpropylaldehyde (boiling point 222°C), hydratropic aldehyde (2-phenylpropanal, boiling point 222°C), phenylethyl formate (boiling point 226°C), geraniol (boiling point 230°C), citronellyl formate (boiling point 235°C), mugol (3,7-dimethyl-4,6-octadien-3-ol, boiling point 237°C), methoxycitronellal (boiling point 238°C), geranyl acetate (boiling point 245°C), cinnamic alcohol (boiling point 250°C), cinnamyl formate (boiling point 252°C), etc. The boiling point values for fragrances are taken from the Good Scents Company website (http: / / www.thegoodscentscompany.com / ) at 760 mmHg. If not specified, the values can be found at https: / / www.chemsrc.com / en / , http: / / www.chemspider.com / , and in "Synthetic Fragrances: Chemistry and Product Knowledge, Revised and Expanded Edition," Chemical Daily Co., Ltd., 2016.
[0029] Even more suitable fragrances are those with boiling points in the range of 120°C to 220°C, such as isoamyl formate (boiling point 123°C), butyl acetate (boiling point 126°C), cis-3-hexenal (boiling point 126°C), 3-methyl-1-butanol (isoamyl alcohol, boiling point 132°C), 1-pentanol (n-amyl alcohol, boiling point 138°C), isoamyl acetate (boiling point 142°C), and trans-2-hexenal 60-3-hexenyl formate (boiling point 146°C), hexyl formate (boiling point 155°C), trans-3-hexenol (boiling point 155°C), cis-3-hexenol (boiling point 156°C), hexyl alcohol (boiling point 156°C), trans-2-hexenol (boiling point 159°C), trimethylhexanal (3,5,5-trimethylhexanal, boiling point 167°C), cis-3-hexenol acetate 3-Hexenyl (boiling point 169°C), Dimitol (boiling point 170°C), Hexyl Acetate (boiling point 172°C), 3-Methyl-3-Methoxybutanol (boiling point 174°C), Heptyl Alcohol (boiling point 175°C), Limonene (boiling point 177°C), Isoamyl Butyrate (boiling point 178°C), Benzaldehyde (boiling point 178°C), Melonal (boiling point 188°C), Cyclobertal (boiling point 189°C), Trimethylhexano Examples include ethanol (boiling point 193°C), dihydromyrcenol (boiling point 194°C), linalool (boiling point 199°C), linalyl formate (boiling point 202°C), benzyl acetate (boiling point 212°C), dimethylbenzylcarbinol (boiling point 215°C), geranyl formate (boiling point 216°C), phenylethyl alcohol (boiling point 219°C), hydratropic alcohol (boiling point 220°C), and linalyl acetate (boiling point 220°C).
[0030] The composition of the present invention preferably contains a fragrance that not only acts as a fragrance indicator but also exhibits a virus inactivation effect. From the viewpoint of virus inactivation, the following fragrances are even more preferable. Isoamyl formate (boiling point 123°C), Butyl acetate (boiling point 126°C), 3-Methyl-1-butanol (boiling point 132°C), 1-Pentanol (boiling point 138°C), Isoamyl acetate (boiling point 142°C), trans-2-hexenal (boiling point 146°C), cis-3-hexenyl formate (boiling point 155°C), trans-3-hexenol (boiling point 155°C), cis-3-hexenol (boiling point 156°C), Hexyl alcohol (boiling point 156°C), trans-2-hexenol (boiling point 159°C), 3,5,5-Trimethylhexanal (trimethylhexanal) (boiling point 167°C), 2,4-Dimethyl-2-heptanol (Dimitol) (boiling point 170°C), 3-Methyl-3-methoxybutanol (boiling point 174°C), Heptyl alcohol (boiling point 175°C), Benzaldehyde (boiling point 178°C), 2,6-Dimethyl-5-heptenal (Melonal) (boiling point 188°C), 3,6-Dimethylcyclohexe-3-ene-1-carboaldehyde (cyclobertal) (boiling point 189°C), 3,5,5-Trimethylhexanol (trimethylhexanol) (boiling point 193°C), Dihydromyrcenol (boiling point 194°C), Linalyl formate (boiling point 202°C), Benzyl alcohol (boiling point 205°C), Benzyl acetate (boiling point 212°C), 2-methyl-1-phenylpropan-2-ol (dimethylbenzylcarbinol) (boiling point 215°C), Phenylate alcohol (boiling point 219°C), 2-Phenylpropanal (hydratropic alcohol) (boiling point 220°C), Phenylpropylaldehyde (boiling point 222°C), Hydratropic aldehyde (boiling point 222°C), Phenylate formate (boiling point 226°C), 3,7-dimethyl-4,6-octadien-3-ol (mugol) (boiling point 237°C), Citronellyl formate (boiling point 235°C), Methoxycitronellal (boiling point 238°C), Cinnamic alcohol (boiling point 250°C), Cinnamyl formate (boiling point 252°C)
[0031] From the viewpoint of fragrance indicator properties and virus inactivation, the composition of the present invention preferably contains a fragrance with a boiling point of 120°C or higher and 260°C or lower in an amount of 0.001 to 1.0% by mass, more preferably 0.01 to 0.5% by mass. The composition may contain other fragrances (with boiling points below 120°C or above 260°C), but the content is preferably 0.5% by mass or less, and more preferably 0.1% by mass or less. Furthermore, in the composition, the proportion of fragrances with boiling points between 120°C and 260°C to the total fragrance is preferably 90% by mass or more, and more preferably 95% by mass or more.
[0032] Furthermore, in the composition of the present invention, A1) the ratio of fragrance with a boiling point of 120°C to 260°C to a diol with a boiling point of 220°C or less and having 2 to 4 carbon atoms (fragrance / diol with a boiling point of 220°C or less and having 2 to 4 carbon atoms) is preferably 0.00001 to 0.1, more preferably 0.0001 to 0.01.
[0033] In addition to the above-mentioned components, the composition of the present invention may contain, in appropriate combinations, additives such as viscosity modifiers like ethanol and isopropanol, non-volatile antiviral and antibacterial agents such as benzalkonium chloride, dialkyldimethylammonium chloride, sodium hypochlorite, hypochlorous acid water, chlorous acid water, and glutaraldehyde, as long as they do not impair the effects of the present invention. For example, chelating agents, humectants, lubricants, builders, buffers, abrasives, electrolytes, bleaches, fragrances, dyes, foaming control agents, corrosion inhibitors, essential oils, thickeners, pigments, gloss enhancers, enzymes, detergents, dispersants, polymers, silicones, and hydrophobic substances. The content of the additives can be appropriately set within a range that does not impair the objectives of the present invention, but it is preferable that the total content of A1) diols with a boiling point of 220°C or less and having 2 to 4 carbon atoms, water, and fragrances in the composition be 80% by mass or more, and more preferably 90% by mass or more. In particular, the aforementioned non-volatile antiviral and antibacterial agents are preferably not included from the viewpoint of reducing human irritation during spraying. If they are included, the amount is preferably 10% by mass or less, more preferably 5% by mass or less, even more preferably 1% by mass or less, and preferably substantially absent. Furthermore, if ethanol is included, from the viewpoint of preventing ignition, it is preferably 10% by mass or less, more preferably 5% by mass or less, even more preferably 1% by mass or less, and preferably substantially absent.
[0034] As shown in the examples below, A1) a composition in which diols with a boiling point of 220°C or less and having 2 to 4 carbon atoms, and water, each within a specific concentration range, is suitable for spraying, and when the composition is sprayed and brought into contact with the influenza virus, the virus can be inactivated. Furthermore, alkyl glyceryl ethers and certain fragrances have been shown to have a virus-inactivating effect, and the virus-inactivating effect is improved by combining these with diols with a boiling point of 220°C or less and having 2 to 4 carbon atoms. Therefore, diols with a boiling point of 220°C or less and having 2 to 4 carbon atoms, as well as combinations of diols with a boiling point of 220°C or less and having 2 to 4 carbon atoms with at least one selected from alkyl glyceryl ethers and specific fragrances, can serve as active ingredients for virus inactivation and can be used to produce virus inactivation compositions for liquid spraying. Furthermore, if a composition containing 40-90% by mass of a diol having 2-4 carbon atoms and 10-60% by mass of water, with a boiling point of 220°C or lower, or a composition containing 40-90% by mass of a diol having 2-4 carbon atoms, 10-60% by mass of water, and at least one selected from alkyl glyceryl ether and a specific fragrance, with a boiling point of 220°C or lower, is sprayed onto an object suspected of viral contamination, the virus in that object can be inactivated.
[0035] The content of A1) diols in the composition having a boiling point of 220°C or lower and having 2 to 4 carbon atoms is 40% by mass or more, preferably 50% by mass or more, more preferably 60% by mass or more, and more preferably 70% by mass or more, from the viewpoint of virus inactivation, and 90% by mass or less, preferably 80% by mass or less, from the viewpoint of spray characteristics. Here, spray characteristics refer to the fact that the composition does not easily remain in the discharge path in the container, and a larger amount of the compound liquid is sprayed onto the target object or space.
[0036] Examples of water include tap water, distilled water, deionized water, and purified water. The water content in the composition is 10% by mass or more, preferably 20% by mass or more, from the viewpoint of spraying characteristics, and 60% by mass or less, preferably 50% by mass or less, and more preferably 40% by mass or less, from the viewpoint of virus inactivation. As described in A1) above, it is preferable to mix and dissolve a diol with a boiling point of 220°C or lower and 2 to 4 carbon atoms with water so that the concentration of the diol and water is such that the diol has a boiling point of 220°C or lower and 2 to 4 carbon atoms is as described above, from the viewpoint of virus inactivation and spray characteristics.
[0037] In the composition, A1) the ratio of diols with a boiling point of 220°C or less and having 2 to 4 carbon atoms to water is, from the viewpoint of virus inactivation, preferably 0.6 to 9.0, more preferably 1.0 to 4.0, even more preferably 1.5 to 4.0, and still more preferably 1.5 to 3.0, in terms of the mass ratio of diols with a boiling point of 220°C or less and having 2 to 4 carbon atoms to water [diols with a boiling point of 220°C or less and having 2 to 4 carbon atoms / water].
[0038] The viscosity of the composition at 20°C is preferably 2 to 40 mPa·s, more preferably 3 to 20 mPa·s, from the viewpoint of spray characteristics. The viscosity can be measured using an ultrasonic viscometer. In use where flammability is not a concern, ethanol and isopropyl alcohol can be included as viscosity modifiers, and if these are included in the composition, their content is preferably about 1 to 10% by mass of the composition.
[0039] The preferred spray volume of the composition is 0.1g to 500g / min, more preferably 10g to 500g / min, and even more preferably 20g to 100g / min. To achieve the above spray volume, it is preferable to use an atomizing nozzle in the sprayer. Alternatively, a spray volume of 0.1g to 1g / min can be achieved using an atomizing device such as a nebulizer, and a spray volume of 50g to 500g / min can be achieved using a diffusion device such as a washer nozzle or misting machine. Furthermore, when spraying in a closed or semi-closed space, the spray volume is preferably 50g to 200g / m² per target space. 3 That is the case.
[0040] The liquid pressure range of the composition supplied to the nozzle of the sprayer is preferably 0.1 MPa or higher, more preferably 0.15 MPa or higher, from the viewpoint of making it easier to spray viscous liquids, and preferably 2.5 MPa or lower, more preferably 0.7 MPa or lower, from the viewpoint of even spraying.
[0041] The diameter of the foreign matter passage through the nozzle of the sprayer (the diameter of the largest sphere that can pass through the smallest flow path in the nozzle) is preferably 0.05 mm or more, more preferably 0.1 mm or more, and even more preferably 0.15 mm or more, from the viewpoint of making it easier to spray viscous liquids. Furthermore, from the viewpoint of even spraying, it is preferably 0.5 mm or less, more preferably 0.4 mm or less, and even more preferably 0.3 mm or less.
[0042] The viruses targeted for virus inactivation in this invention include all types of viruses, regardless of the type of nucleic acid (RNA, DNA) and whether or not they have an envelope. Enveloped viruses include those with RNA as their nucleic acid, such as influenza virus, coronavirus, SARS coronavirus, SARS coronavirus-2, RSV, mumps virus, lassa virus, dengue virus, rubella virus, and human immunodeficiency virus, and those with DNA as their nucleic acid, such as human herpesvirus, vaccinia virus, and hepatitis B virus. Furthermore, examples of viruses that do not have an envelope include those with RNA as their nucleic acid, such as norovirus, poliovirus, echovirus, hepatitis A virus, hepatitis E virus, rhinovirus, astrovirus, rotavirus, coxsackievirus, enterovirus, and sapovirus, and those with DNA as their nucleic acid, such as adenovirus, B19 virus, papovavirus, and human papillomavirus.
[0043] Of these, viruses having an envelope are preferred, viruses having an envelope and RNA as their nucleic acid are more preferred, and influenza virus, human coronavirus, SARS coronavirus, and SARS coronavirus-2 are even more preferred. SARS-CoV-2 (Severe acute respiratory syndrome coronavirus 2) is a SARS-related coronavirus that causes acute respiratory illness (COVID-19).
[0044] 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 then 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.
[0045] Objects of concern regarding viral contamination include the skin or mucous membranes of animals to which the virus may adhere, hard or soft surfaces of inanimate objects, waste materials, and spaces in which the virus may be airborne or dispersed. Examples of inanimate object surfaces include hard surfaces in homes and business facilities such as counters, sinks, restrooms, toilets, bathtubs, showers, floors, windows, doorknobs, walls, drains, and pipes; hard surfaces of kitchen utensils, furniture, telephones, toys, and other various appliances, tools, and miscellaneous goods; and soft surfaces of textile products (carpets, area rugs, curtains, fabric furniture, clothing, masks, etc.). Examples of waste include general waste (household waste such as food scraps, tissues, and masks) and industrial waste (sludge, human waste, medical waste, etc.). If the waste is contained in a bag, the spray can be applied to the surface of the bag. Furthermore, examples of spaces include: the interiors of ordinary homes such as dining kitchens, bedrooms, children's rooms, bathrooms, and toilets; the interiors of facilities such as shops, restaurants, inns, hospitals, workshops, livestock barns, factories, welfare facilities, educational facilities, movie theaters, museums, and karaoke boxes; the interiors of vehicles such as automobiles (garbage trucks, buses, etc.), trains, and airplanes; and semi-enclosed spaces (lockers, storage rooms, closets, etc.; storage boxes (for toys, karaoke microphones, dishes, condiments, writing instruments, and stationery)).
[0046] Methods for spraying the composition include, for example, filling known spray containers such as trigger spray containers (direct pressure or stored pressure type), dispenser-type pump spray containers, and aerosol spray containers equipped with pressure-resistant vessels, and spraying by appropriately adjusting the spray volume. Another method involves filling atomizing devices such as pressurized air atomizing sprayers (electric or manual), nebulizers, and diffusers, and diffusion devices such as washer nozzles and misting machines, and spraying them into a space where viruses are present. In this invention, these containers and devices are also referred to as sprayers. Furthermore, if you do not want to get the object, which may be contaminated with a virus, too wet, you can place the object and a carrier that will temporarily receive the composition in a sealed space, spray the composition onto the carrier, and then vaporize a diol with a boiling point of 220°C or less and 2 to 4 carbon atoms from there, filling the container with the resulting diol, which will indirectly treat the object. The timing for placing the carrier and the target object into a sealed space, and the timing for spraying the composition onto the carrier, can be set arbitrarily. As the carrier, materials with a large surface area, such as foamed sponge, nonwoven fabric, or paper, are preferred, as they have a boiling point of 220°C or lower and allow for easy vaporization of diols with 2 to 4 carbon atoms.
[0047] The following describes, in particular, a method of spraying the composition towards objects suspected of viral contamination in a garbage truck. A garbage truck is equipped with an input port for loading collected waste and a cargo box for storing the loaded waste. When workers put waste into the input port, or when scooping or pushing the waste into the loading box, the bags containing the waste may rupture. If the waste contained in the ruptured bag is contaminated with a virus, the virus may spread into the air near the input port, raising concerns about virus exposure to workers operating the garbage truck. From the viewpoint of reducing the possibility of workers in garbage trucks being exposed to the virus, it is preferable to spray the composition towards the inlet. Furthermore, from the viewpoint of evenly spraying the target area where viral contamination is suspected, it is preferable to spray from the top of the inlet towards the bottom and / or inside of the side of the inlet. Furthermore, it is preferable that the spraying timing coincides with the operation of the scraping device or the pushing device.
[0048] The following describes, in particular, a method of spraying the composition towards objects suspected of viral contamination within livestock barns. Inside the livestock barn, it is preferable to install multiple sprayers on the ceiling and spray downwards. The number of sprayers to be installed inside the livestock barn should be 100m 2 From the viewpoint of evenly spraying the area, it is preferable to use one or more, more preferably two or more, and even more preferably three or more. From an economic viewpoint, it is preferable to use 30 or fewer, more preferably 20 or fewer, and even more preferably 10 or fewer. The timing of spraying depends on the livestock barn; it can be done as soon as viral contamination is detected (for example, when avian influenza infection is confirmed), or it can be done preventively.
[0049] The average particle size of the sprayed particles is preferably 5 μm or more, more preferably 10 μm or more, and even more preferably 50 μm or more, from the viewpoint of minimizing the influence of airflow so that spraying can be performed on the target location. Furthermore, from the viewpoint of evenly spraying while minimizing the amount of composition used and facilitating volatilization to inactivate viruses in the space, it is preferably 500 μm or less, more preferably 200 μm or less, even more preferably 150 μm or less, and even more preferably 100 μm or less. Here, the average particle size of the sprayed particles is the volume-based median diameter (D50) measured by a laser diffraction particle analyzer, which can be measured by the method described in the examples below.
[0050] In the present invention, it is preferable to spray the composition without heating it (in an unheated state) in order to appropriately deliver the composition to the surface or space of an object where viral contamination is a concern, in other words, to prevent loss due to the vaporization of diols with a boiling point of 220°C or lower and having 2 to 4 carbon atoms before reaching the target. Methods for spraying in an unheated state include spraying methods using trigger-type sprayers, nebulizers, misting machines, washer nozzles, etc., as described above. The temperature of the composition when spraying is preferably 20 to 40°C. In other words, the present invention allows for virus inactivation without heating, providing a safer method for virus inactivation. Furthermore, because spraying is used, the composition can be applied more precisely to the target object. When spraying a composition onto an object without heating, the distance between the nozzle from which the composition is sprayed and the object is preferably within 3m, and more preferably within 1m, from the viewpoint of efficiently delivering the composition to the object and maximizing virus inactivation. In particular, when a diol with a boiling point of 220°C or lower and having 2 to 4 carbon atoms is sprayed onto a carrier and then vaporized to inactivate the virus, it is preferable to spray the carrier at a distance of preferably within 50cm, more preferably within 30cm, from the viewpoint of preventing the composition from adhering to the surroundings.
[0051] After spraying the composition, it is preferable to leave it for 30 minutes or more to allow the virus to come into contact with the diol, which has a boiling point of 220°C or lower and has 2 to 4 carbon atoms, and to fully exhibit its virus inactivation effect.
[0052] In the present invention, when performing virus inactivation of a space, the concentration of A1) a diol with a boiling point of 220°C or lower and having 2 to 4 carbon atoms in the target space is preferably 20 ppm (volume concentration, the same applies hereinafter) or more, more preferably 50 ppm or more, even more preferably 70 ppm or more, even more preferably 74 ppm or more, even more preferably 80 ppm or more, even more preferably 84 ppm or more, and even more preferably 87 ppm or more, from the viewpoint of virus inactivation. A1) The boiling point is 220°C or lower. Among diols with 2 to 4 carbon atoms, the relationship between the concentration of 1,2-propanediol in the air and virus inactivation can be investigated by the following method. When the concentration in the air is 87 ppm, the virus inactivation effect is 99%, and when the concentration in the air is 20 ppm, the virus inactivation effect is 53%. Also, based on the regression equation from several measurement results, the concentration (predicted value) that exhibits the desired virus inactivation effect can be determined. In addition, the same method can be applied to diols other than 1,2-propanediol that have a boiling point of 220°C or lower and 2 to 4 carbon atoms.
[0053] 1. Method Influenza A virus (A / Puerto Rico / 8 / 1934, H1N1) strain was used as the test virus strain. A cotton ball soaked with 1000 μL of 1,2-propanediol was placed statically on the bottom of a 1 L glass bottle manufactured by Tokyo Glass Kikai Co., Ltd., and the operation of stirring at a rotation speed of 500 rpm for 30 minutes at about 23°C using a stirrer was performed. Alternatively, a glass bottle with 1 μL of an aqueous 1,2-propanediol solution (0.3 g / mL) dropped on the bottom was left standing in a 60°C constant temperature bath for 30 minutes, and then left standing at about 23°C for 30 minutes, and the operation of stirring at a rotation speed of 500 rpm using a rotor and a stirrer was performed. By these operations, the concentration of 1,2-propanediol in the air was balanced. 1.5 μL (8.3×10 5 FFU) of influenza virus was dried on the lid of the tube for 30 minutes. The lid with the attached virus was quickly placed into the glass bottle, and the virus and 1,2-propanediol were reacted at room temperature (about 23°C) for 30 minutes. At that time, a state where the 1,2-propanediol and the virus did not directly contact was maintained. After the reaction, the virus was recovered with a medium and inoculated into MDCK cells (derived from canine kidney tubular epithelial cells) that had been cultured in a 12-well plate in advance. After culturing for about 18 hours under the conditions of 37°C and 5% CO2, the number of formed foci was measured, and the virus infectivity titer was measured. The infectivity titer when reacted with the control mineral oil was set as 100%, and the virus inactivation activity of 1,2-propanediol was calculated from the following formula (5). The test was performed 3 times. Virus inactivation effect = -Log[1,2-propanediol infectivity titer / control infectivity titer] (5)
[0054] When measuring the spatial concentration of 1,2-propanediol, a special analytical lid with a 3.5 mm diameter hole was used. The lid was left to stand for 30 minutes under virus-free conditions, and a gas collection tube fitted with a PTFE tube (manufactured by Nichias Corporation) was inserted through the hole in the lid to determine the spatial concentration of 1,2-propanediol. The analytical method and conditions are as described in the examples below.
[0055] In the present invention, from the viewpoint of virus inactivation, A1) the preferred concentration of a diol having a boiling point of 220°C or lower and having 2 to 4 carbon atoms on the target surface is 0.14 mg / cm³. 2 The above results indicate that a more preferred concentration is 0.20 mg / cm³. 2 More preferably 0.25 mg / cm³ 2 That's all. To measure the concentration of diols with a boiling point of 220°C or lower and containing 2 to 4 carbon atoms on a target surface, the diols can be collected on the surface using a glass or plastic petri dish, then extracted with a common solvent such as methanol, ethanol, or acetone, and finally the concentration can be determined by gas chromatography-mass spectrometry (GC / MS).
[0056] With regard to the embodiments described above, the present invention further discloses the following aspects.
[0057] <1> A virus inactivation composition for liquid spraying, comprising A1) a composition containing 40-90% by mass of a diol having 2-4 carbon atoms and a boiling point of 220°C or lower, and 10-60% by mass of water.
[0058] <2> A1) A method for inactivating viruses, comprising spraying a composition containing 40-90% by mass of a diol having 2-4 carbon atoms and a boiling point of 220°C or lower, and 10-60% by mass of water, onto the hard or soft surface of an inanimate object suspected of viral contamination, or onto waste.
[0059] <3> A1) A method for inactivating viruses in a target space, comprising spraying a composition containing 40-90% by mass of a diol having 2-4 carbon atoms and a boiling point of 220°C or lower, and 10-60% by mass of water, onto a carrier, and vaporizing the composition from the carrier so that the concentration of A1) a diol having 2-4 carbon atoms and a boiling point of 220°C or lower in the space becomes 20 ppm or higher.
[0060] <4> The composition further contains A2) a glycol ether having a boiling point of 220°C or lower and having 6 carbon atoms. <1> ~ <3> The composition or method described in any of the following. <5> The composition contains, preferably, 1% by mass or more, more preferably 3% by mass or more, even more preferably 7% by mass or more, and also preferably 40% by mass or less, more preferably 30% by mass or less, even more preferably 20% by mass or less, even more preferably 15% by mass or less, and even more preferably 10% by mass or less. <4> The composition or method described above. <6> In the composition, the mass ratio [A2) / (A1)+A2)) of A2) glycol ether having a boiling point of 220°C or less and 6 carbon atoms to the total amount of A1) diol having a boiling point of 220°C or less and 2 to 4 carbon atoms, is preferably 0.05 or more, more preferably 0.1 or more, even more preferably 0.15 or more, and also preferably 1.0 or less, more preferably 0.5 or less, and even more preferably 0.3 or less. <4> or <5> The composition or method described above. <7> The composition further contains A3) alkylglyceryl ether <1> ~ <3> The composition or method described in any of the following. <8> The content of A3) alkylglyceryl ether in the composition is preferably 0.1% by mass or more, more preferably 0.2% by mass or more, even more preferably 0.4% by mass or more, and also preferably 2% by mass or less, more preferably 1% by mass or less, even more preferably 0.9% by mass or less, and even more preferably 0.8% by mass or less. <7> The composition or method described above. <9> In the composition, the mass ratio of A3) alkyl glyceryl ether to A1) diol having a boiling point of 220°C or less and having 2 to 4 carbon atoms [A3) / A1)] is preferably 0.001 or more, more preferably 0.005 or more, even more preferably 0.01 or more, and also preferably 0.1 or less, more preferably 0.05 or less, even more preferably 0.04 or less, and even more preferably 0.03 or less. <7> or <8> The composition or method described. <10> The composition further contains at least one fragrance selected from the following: <1> ~ <3> The composition or method described in any of the following. Isoamyl formate (boiling point 123°C), Butyl acetate (boiling point 126°C), 3-Methyl-1-butanol (boiling point 132°C), 1-Pentanol (boiling point 138°C), Isoamyl acetate (boiling point 142°C), trans-2-hexenal (boiling point 146°C), cis-3-hexenyl formate (boiling point 155°C), trans-3-hexenol (boiling point 155°C), cis-3-hexenol (boiling point 156°C), Hexyl alcohol (boiling point 156°C), trans-2-hexenol (boiling point 159°C), 3,5,5-Trimethylhexanal (boiling point 167°C), 2,4-dimethyl-2-heptanol (boiling point 170°C), 3-Methyl-3-methoxybutanol (boiling point 174°C), Heptyl alcohol (boiling point 175°C), Benzaldehyde (boiling point 178°C), 2,6-dimethyl-5-heptenal (boiling point 188°C), 3,6-Dimethylcyclohexe-3-ene-1-carboaldehyde (boiling point 189°C), 3,5,5-Trimethylhexanol (boiling point 193°C), Dihydromyrcenol (boiling point 194°C), Linalyl formate (boiling point 202°C), Benzyl alcohol (boiling point 205°C), Benzyl acetate (boiling point 212°C), 2-methyl-1-phenylpropan-2-ol (boiling point 215°C), Phenylate alcohol (boiling point 219°C), 2-Phenylpropanal (boiling point 220°C), Phenylpropylaldehyde (boiling point 222°C), Hydratropic aldehyde (boiling point 222°C), Phenylate formate (boiling point 226°C), 3,7-dimethyl-4,6-octadien-3-ol (boiling point 237°C), Citronellyl formate (boiling point 235°C), Methoxycitronellal (boiling point 238°C), Cinnamic alcohol (boiling point 250°C), and Cinnamyl formate (boiling point 252°C) <11> The content of the fragrance in the composition is preferably 0.001% by mass or more, more preferably 0.01% by mass or more, and also preferably 1.0% by mass or less, more preferably 0.5% by mass or less. <10> The composition or method described above. <12> A1) In the composition, the ratio of the fragrance to a diol having a boiling point of 220°C or less and having 2 to 4 carbon atoms (fragrance / diol having a boiling point of 220°C or less and having 2 to 4 carbon atoms) is preferably 0.00001 or more, more preferably 0.0001, and also preferably 0.1 or less, more preferably 0.01 or less. <10> or <11> The composition or method described above. <13> The composition further contains A2) a glycol ether having a boiling point of 220°C or lower and 6 carbon atoms, and at least one fragrance selected from the following: <1> ~ <3> The composition or method described in any of the following. Isoamyl formate (boiling point 123°C), Butyl acetate (boiling point 126°C), 3-Methyl-1-butanol (boiling point 132°C), 1-Pentanol (boiling point 138°C), Isoamyl acetate (boiling point 142°C), trans-2-hexenal (boiling point 146°C), cis-3-hexenyl formate (boiling point 155°C), trans-3-hexenol (boiling point 155°C), cis-3-hexenol (boiling point 156°C), Hexyl alcohol (boiling point 156°C), trans-2-hexenol (boiling point 159°C), 3,5,5-Trimethylhexanal (boiling point 167°C), 2,4-dimethyl-2-heptanol (boiling point 170°C), 3-Methyl-3-methoxybutanol (boiling point 174°C), Heptyl alcohol (boiling point 175°C), Benzaldehyde (boiling point 178°C), 2,6-dimethyl-5-heptenal (boiling point 188°C), 3,6-Dimethylcyclohexe-3-ene-1-carboaldehyde (boiling point 189°C), 3,5,5-Trimethylhexanol (boiling point 193°C), Dihydromyrcenol (boiling point 194°C), Linalyl formate (boiling point 202°C), Benzyl alcohol (boiling point 205°C), Benzyl acetate (boiling point 212°C), 2-methyl-1-phenylpropan-2-ol (boiling point 215°C), Phenylate alcohol (boiling point 219°C), 2-Phenylpropanal (boiling point 220°C), Phenylpropylaldehyde (boiling point 222°C), Hydratropic aldehyde (boiling point 222°C), Phenylate formate (boiling point 226°C), 3,7-dimethyl-4,6-octadien-3-ol (boiling point 237°C), Citronellyl formate (boiling point 235°C), Methoxycitronellal (boiling point 238°C), Cinnamic alcohol (boiling point 250°C), and Cinnamyl formate (boiling point 252°C) <14> The composition further contains A3) alkylglyceryl ether <13> The composition or method described above. <15> The hard or soft surface of an inanimate object suspected of viral contamination, or the waste, is preferably the hard or soft surface of a garbage truck, or the waste itself. <2> , <4> ~ <14> One of the methods described above. <16> The composition is preferably sprayed from the top of the garbage truck's inlet toward the bottom and / or inside of the sides of the inlet. <15> Methods used. [Examples]
[0061] Examples 1-7 and Comparative Examples 1-3: Inactivation of influenza virus Compositions prepared by mixing 1,2-propanediol (PG) with water to the concentrations shown in Table 1 were used to perform virus inactivation tests in a 36L acrylic container (product name: AS ONE Suction Box 10L, 350×490×240mm). In Examples 5, 6, and 7, the fragrance compositions shown in Table 2 a) to c) were further mixed in. Influenza virus type A (A / Puerto Rico / 8 / 1934,H1N1) strain was used as the test virus strain. Specifically, the composition is sprayed into the container three times for 1 minute each (with a 2-minute 30-second interval) using a compressor-type nebulizer (NE-C803, manufactured by Omron, median particle size of sprayed particles approximately 5 μm), while simultaneously the influenza virus solution (5 × 10) is sprayed. 6 The FFU / mL solution was sprayed using a compressor-type nebulizer for 3 minutes, and then allowed to stand for 3 minutes. The total discharge volume for 3 one-minute sessions was 0.63g to 0.79g per 36L. Viruses floating in the container space were collected using an aspirator into a total of 3 mL of serum-free medium in a bubbler for 2 minutes. Viruses that fell onto a dish pre-placed at the bottom of the acrylic container were collected in 3 mL of serum-free medium. After diluting the collected virus solution, it was inoculated into MDCK cells (derived from canine renal tubular epithelial cells) that had been pre-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 virus inactivation effect was determined using the following formula (1). A higher value indicates a better virus inactivation effect, and in this example, a value of less than 30% was considered ineffective. Virus inactivation effect (%) = [1 - (Number of infected cells when test sample is sprayed / Number of infected cells when comparative example 1 (water) is sprayed)] × 100 (1)
[0062] Furthermore, the spray characteristics were determined from the nebulizer's spray weight using the following formula (2), and anything less than 90% was considered defective. Spray characteristics (%) = (Spray weight of test sample / Spray volume of Example 3) × 100 (2)
[0063] The surface concentration of 1,2-propanediol that fell onto the target surface was determined by adding 5 ml of methanol dropwise to the compositions of Comparative Examples 1-3 and Examples 1-7 that fell onto the surface of a 5 cm diameter plastic petri dish, and then determining the abundance of 1,2-propanediol in the extracted solution by GC / MS.
[0064] The results are shown in Tables 1 and 2.
[0065] [Table 1]
[0066] [Table 2]
[0067] As shown in Table 1, the compositions of Examples 1 to 7 had good spraying characteristics, and when the compositions were sprayed, a virus inactivation effect of 30% or more was exhibited against either or both of the floating viruses on the object surface or in the space. Furthermore, as shown in Table 2, the virus inactivation effects were improved in Examples 5, 6, and 7 in which fragrances having a virus inactivating action were mixed.
[0068] Example 8 Assuming the inlet of a garbage truck (about 1 m for a medium-sized truck) where there is a risk of virus infection when the garbage bursts 3 , a test was conducted to determine whether the effective concentration was reached using a composition with a 1,2-propanediol concentration of 80% by mass and a water concentration of 20% by mass. A 2 m stainless space with a door 3 was used. A total of 40 g of the composition was sprayed onto three sides and the bottom surface using a trigger spray. The median diameter (D50) based on volume of the composition of Example 8 measured according to the following conditions was 89.0 μm for this spraying. <Measurement conditions for D50> Laser diffraction particle size distribution measuring device (manufacturer: Malvern, Spraytec), used lens 300 mm Spraying direction: Sprayed horizontally Measurement area: The measuring device was arranged so that the point 15 cm horizontally (spraying direction) from the spray outlet of the sprayer was the measurement area. Sampling time: 1 s After spraying, the door was closed and left as it was. When analyzing the gas, the 1,2-propanediol concentration in the space was collected by inserting a gas collection tube (Tenax (registered trademark) TA: manufactured by GERSTEL) through a hole in the door and sucking the internal air at a suction rate of 100 mL / min for 1 minute. The collected air was analyzed using a gas chromatograph-mass spectrometer (GC / MS) with a thermal desorption system. The GC / MS analysis conditions were as follows: GC column: DB-WAX (Agilent), heating conditions: 40°C (hold for 3 minutes) - 6°C / min - 70°C - 3°C / min - 240°C. For PG quantification, a fixed amount of methanol dilution was injected into a Tenax adsorption tube, and then analyzed using the GC / MS with a thermal desorption system as described above. A calibration curve was created from the detected values. As a result, it was confirmed that the concentration of 1,2-propanediol in the space reached 84 ppm after 30 minutes.
[0069] Example 9 Assuming a toy box where there is a risk of viral infection through preschoolers and children, a test was conducted to see if an effective concentration could be reached using a composition with a 1,2-propanediol concentration of 80% by mass and a water concentration of 20% by mass. A commercially available 68L polypropylene storage box was used, with 10 sponges placed at the bottom. The composition was sprayed from 30cm above the sponges at a total of 16g (20 sprays) or 24g (30 sprays) using a trigger sprayer. A wire mesh was then placed on top, followed by the placement of 20 toys, and the box was closed and left to stand. The concentration of 1,2-propanediol in the storage box was measured in the same manner as in Example 8. As a result, it was confirmed that after 6 hours, the concentration of 1,2-propanediol in the storage box reached 50 ppm after 20 sprays and 74 ppm after 30 sprays.
[0070] Examples 10-12 The spraying characteristics of a sprayer were tested, simulating application to the waste loading port of a garbage truck. The sprayer itself was a Koshin Mr. Auto 2.5L pressurized air atomizing sprayer (maximum pressure approximately 0.3 MPa), and the nozzle tip was changed to an atomizing nozzle (Ikeuchi Co., Ltd., hollow conical nozzle KB80125N: foreign matter passage diameter 0.3 mm). The spray liquid was prepared using the formulations shown in Examples 10 to 12 in Table 3. As a result, all of them were able to be sprayed in a conical shape without any problems.
[0071] [Table 3]
[0072] Examples 13 and 14 A2) The effect of improving the spraying characteristics of the component addition was tested. The sprayer body used was the Mister Auto 2.5L manufactured by Koushin (maximum pressure: approximately 0.3 MPa), and the tip nozzle part used an atomizing nozzle (manufactured by Ikeuchi Co., Ltd., hollow cone nozzle KB8010N: foreign matter passing diameter 0.25 mm). For the spray liquid, in Example 13, a mixed solution with a 1,2-propanediol concentration of 60% by mass and a water concentration of 40% by mass was used, and in Example 14, a mixed solution with a 1,2-propanediol concentration of 60% by mass, a diethylene glycol monoethyl ether concentration of 10% by mass, and a water concentration of 30% by mass was prepared. Using a metal stand, the nozzle part was fixed so that the height was 30 cm, and it was sprayed vertically downward for 10 seconds, and the diameter of the circle of the wet part obtained on the bottom surface was measured. As a result, Example 14 showed a finer and more stable spraying pattern. The diameters were 20 cm for Example 13 and 23 cm for Example 14. It was shown that the conical spraying pattern could be improved by adding the A2) component. In addition, the median diameter (D50) based on volume of the mixed solution of Example 13 measured according to the following conditions was 75.0 μm. <Measurement conditions for D50> Laser diffraction particle size distribution measuring device (manufacturer: manufactured by Malvern, Spraytec), lens used: 300 mm Spraying direction: Spray in the horizontal direction Measurement area: The measuring device was arranged so that the point 15 cm horizontally (spraying direction) from the spray outlet of the sprayer became the measurement area. Sampling time: 1 s For comparison, instead of the above spraying, the mixed solution of Example 13 was sprayed using the compressor type nebulizer (NE-C803, manufactured by Omron) used in Example 1. Specifically, using the same metal stand as above, the nozzle part was fixed so that the height was 30 cm. Since the ejection direction is horizontal in the state of the product, a hose bent in a crank shape was connected so that it could be sprayed vertically downward, and it was sprayed vertically downward for 10 seconds. As a result, the sprayed particles diffused at a distance of approximately 20 cm from the nozzle, and no stable spray pattern was observed on the landing surface. The volume-based median diameter (D50) of the spray, measured under the above conditions, was 4 μm.
[0073] Examples 15 and 16 (Virus inactivation test by spraying) 1. Method A virus inactivation test was performed in a 36L acrylic container (product name: AS ONE Suction Box 10L, 350 x 490 x 240 mm). Influenza virus type A (A / Puerto Rico / 8 / 1934, H1N1) strain was used as the test virus strain. Influenza virus solution (1.8 x 10⁻⁶) 8 The FFU / mL was atomized using a compressor-type nebulizer (NE-C803, Omron). The composition was prepared by mixing 1,2-propanediol (PG, Fujifilm Wako Pure Chemical Industries, Ltd.) and 2-ethylhexylglyceryl ether (GE-EH, Fujifilm Wako Pure Chemical Industries, Ltd.) with water to the concentrations (mass%) shown in Table 4, and then atomized into an acrylic container through a hole in the center of the lid using a sprayer. The sprayer body used was a Koshin Mr. Auto 2.5L (maximum pressure approximately 0.3 MPa), and the tip nozzle was changed to a fine mist nozzle (Ikeuchi Co., Ltd., hollow conical nozzle KB8010N: foreign matter passage diameter 0.25 mm). Specifically, the composition was sprayed alternately in an acrylic box for 5 seconds, followed by the virus for 10 seconds, then the composition again for 5 seconds, followed by the virus for 10 seconds, and finally the composition again for 5 seconds, and the mixture was allowed to stand. Fifteen minutes after the start of the test, the virus that had fallen onto four 3 cm diameter dishes (manufactured by AGC Technoglass Co., Ltd.) that had been placed on the bottom of the acrylic container beforehand was collected in 1.2 mL of serum-free culture medium (manufactured by Thermo Fisher Scientific Co., Ltd.) per dish. After diluting the collected virus solution, it was used to infect MDCK cells (derived from canine renal tubular epithelial cells) that had been cultured in a 12-well plate beforehand, and the viral titer was measured using a Focus Forming Assay. Specifically, after culturing for approximately 18 hours under conditions of 37°C and 5% CO2, the number of foci formed was measured to determine the viral infectivity titer. Using the infectious titer when reacted with water as a control, the virus inactivating effect of the composition was determined by the following formula (7). Virus inactivating effect (Log reduction amount) = -Log 10 [Infectious titer at the time of spraying the composition / Infectious titer of the control](7)
[0074] Also, the viscosities of the compositions of Example 15 and Example 16 shown in Table 4 were measured under the following conditions. <Measurement conditions for viscosity> · Apparatus: Ultrasonic viscometer (manufactured by Marutasu Kogyo Co., Ltd., ViscoTec) · Measurement temperature: 20 °C · Filling amount into the sensor part: Approximately 0.2 g
[0075] Also, after spraying, the median diameter (D50) of the spray liquid on a volume basis of each composition shown in Table 4 was measured according to the following conditions. <Measurement conditions for D50> Laser diffraction particle size distribution measuring device (manufacturer: manufactured by Malvern Co., Ltd., Spraytec), used lens 300 mm Spraying direction: Spraying in the horizontal direction Measurement area: The measuring device was arranged so that the point 15 cm horizontally (spraying direction) from the spray outlet of the sprayer became the measurement area Sampling time: 1 s
[0076] The results are shown in Table 4. The results show the average of four dishes. The higher the numerical value, the better the virus inactivating effect. The detection limit of this test is 99.97% (3.56 Log reduction amount), and the activity value of the sample (P.G. 40% by mass + GE-EH 0.7% by mass) where the detected amount of virus titer was below the detection limit was shown as >99.97 (>3.56).
[0077]
Table 4
[0078] Formulation Examples 1 and 2 for virus inactivating compositions for liquid spraying and Reference Example 1 Inactivation of influenza virus in the liquid phase 1. Method Influenza virus strain A (A / Puerto Rico / 8 / 1934, H1N1) was used as the test virus strain. Sample solutions were prepared so that the final concentration (v / v%) was as shown in Table 4 below. Influenza virus solution (6.0 × 10⁶) in Hybridoma-SFM medium (Thermo Fisher Scientific) as the solvent. 5 5 μL of FFU and 45 μL of the sample solution were reacted at room temperature (approximately 23°C) for 5 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 pre-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 assess the virus inactivation effect. The infectivity titer when reacted with water was used as a control, and the virus inactivation effect of each sample solution was calculated using the following formula (6). The test was performed the following number of times. Virus inactivation effect = -Log[Infectivity titer of sample solution / Infectivity titer of control] (6)
[0079] 2.Results The results are shown in Table 5. For studies where multiple tests were conducted, the average value is shown with two significant figures. As shown in Table 5, 2-ethylhexylglyceryl ether was found to have a virus-inactivating effect, and the virus-inactivating effect was improved in the composition of Formulation Example 2, which was mixed with 2-ethylhexylglyceryl ether. As a result, it is understood that a composition containing A1) 40-90% by mass of a diol having 2-4 carbon atoms and a boiling point of 220°C or lower, 10-60% by mass of water, and A3) an alkyl glyceryl ether is useful as a virus inactivation composition for liquid spraying.
[0080] [Table 5]
[0081] Reference Example 2: Aroma Indicator Test 1. Method Compositions A to M, prepared by mixing 1,2-propanediol (PG) with water and fragrance to the concentrations shown in Table 6, were placed in trigger containers and tested as fragrance indicators. Specifically, 40L garbage bags were filled with paper waste and left outdoors (at approximately 15°C). Each garbage bag surface was sprayed 10 or 20 times from an oblique angle above, and the fragrance intensity was evaluated from a distance of 30 cm immediately after spraying, 30 minutes later, and 60 minutes later, according to the following 6-level odor intensity scale. Compositions with an odor intensity of 2.5 or higher immediately after spraying and a decrease to 1 or less after 30 or 60 minutes were judged to be suitable as indicators. Compositions with an odor intensity above 1 were judged to be unsuitable. (6-level odor intensity scale) 0: Odorless, 1: Barely detectable odor, 2: Weak odor that can be identified, 3: Easily detectable odor, 4: Strong odor, 5: Intense odor
[0082] 2.Results The results are shown in Table 6.
[0083] [Table 6]
[0084] Reference Example 3: Inactivation of influenza virus by fragrances 1. Method Influenza virus type A (A / Puerto Rico / 8 / 1934, H1N1) strain was used as the test virus strain. 75 μL of the fragrance shown in Table 7 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 added. 5The 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 fragrance compound and virus were reacted at room temperature (approximately 23°C) for 30 minutes. During this time, the fragrance 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 fragrance 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 viral inactivation activity of each fragrance was calculated using the following formula (3), with the infectivity titer when reacted with mineral oil as a control. The test was performed three times. Virus inactivation effect = -Log[infectivity titer of fragrance / infectivity titer of control] (3)
[0085] 2.Results The results are shown in Table 7. The average of the three trials is shown with one significant figure.
[0086] [Table 7]
[0087] Reference Example 4: Inactivation of coronavirus by the present invention 1. Method SARS-CoV-2 JPN / Kanagawa / KUH003 was used as the test virus strain. 27 μL of a solution with the composition shown in Table 7 was mixed with 3 μL of virus suspension. The mixture was allowed to react at room temperature for 5 minutes. After 5 minutes, it was diluted 10-fold using cell maintenance medium (Dulbecc's modified Eagle medium (Nacalai Tesque Co., Ltd.) with 2% fetal bovine serum, 100 U / mL penicillin, 100 μg / mL streptomycin, and 1 mg / mL Geneticin G418), and then serially diluted 3-fold using cell maintenance medium. 100 μL of the diluted reaction solution was inoculated into each well of VeroE6 / TMPRSS2 cells that had been previously cultured in a 96-well plate, and the cells were infected at 37°C under 5% CO2 conditions for approximately 1 hour. After infection, all dilution was removed, the wells were washed twice with cell maintenance medium, and fresh cell maintenance medium was added for 3 days. After culturing, the presence or absence of morphological changes in cells (cytopathic effect: CPE) was observed using an inverted phase-contrast microscope, and the 50% tissue culture infectious dose (TCID) was determined by the Behrens-Karber method. 50 The infectivity titer was calculated and converted to the viral infectivity titer per 1 mL of reaction solution. The infectivity titer when reacted with water was used as a control, and the viral inactivation activity of each solution was calculated using the following formula (4). The test was performed three times. Virus inactivation effect = control logTCID 50 / mL - logTCID of reaction solution 50 [Infectious titer of control / mL] (4)
[0088] 2.Results The results are shown in Table 8.
[0089] [Table 8]
Claims
1. A1) A method for inactivating viruses, comprising spraying a composition having a boiling point of 220°C or lower and containing 40 to 90% by mass of a diol having 2 to 4 carbon atoms and 10 to 60% by mass of water onto a surface of an object that is likely to be contaminated with viruses.
2. 2. The method for inactivating a virus according to claim 1, wherein the spraying method is a non-heating method.
3. 2. The method for inactivating a virus according to claim 1, wherein spraying is carried out using a sprayer selected from the group consisting of a pressurized air atomizing spray device, an atomizing device, and a diffusing device.
4. 4. The virus inactivation method according to claim 3, wherein the average particle diameter of the sprayed particles at a point 15 cm away from the nozzle of the sprayer in the spraying direction is 5 μm or more and 500 μm or less.
5. The virus inactivation method according to claim 1, wherein the composition is sprayed at an amount of 0.1 g to 500 g / min.
6. 3. The method for inactivating viruses according to claim 2, wherein when the composition is sprayed onto an object in an unheated state, the distance between the object and the nozzle for spraying the composition is within 3 m.
7. The method for inactivating a virus according to any one of claims 1 to 6, wherein the virus is an enveloped RNA virus.
8. A1) a method for inactivating viruses in a target space, comprising spraying a composition onto a carrier, the composition comprising 40 to 90% by mass of a diol having 2 to 4 carbon atoms and a boiling point of 220°C or less, and 10 to 60% by mass of water, and vaporizing the composition from the carrier so that the concentration of A1) the diol having 2 to 4 carbon atoms and a boiling point of 220°C or less in the space is 20 ppm or more.
9. A virus inactivating composition for liquid spray, comprising: A1) a composition having a boiling point of 220°C or lower and containing 40 to 90% by mass of a diol having 2 to 4 carbon atoms and 10 to 60% by mass of water.
10. The composition of claim 9, further comprising A3) an alkyl glyceryl ether.
11. The composition according to claim 9, further comprising a fragrance having a boiling point of 120°C or higher and 260°C or lower.
12. The composition according to any one of claims 9 to 11, wherein the composition has a viscosity at 20°C of 2 to 40 mPa·s.