Non-enveloped virus inactivation composition
Patent Information
- Application Number
- JP2022206900
- Authority / Receiving Office
- JP · JP
- Patent Type
- Applications
- Current Assignee / Owner
- Priority Date
- 2022-01-31
- Filing Date
- 2022-12-23
- Publication Date
- 2025-09-17
AI Technical Summary
Current disinfectants are ineffective against non-enveloped viruses like norovirus due to their strong physicochemical resistance, and existing compositions are either irritating or corrosive, limiting their use in environments such as homes and food handling facilities.
A composition comprising a cationic surfactant and an aliphatic alcohol with a specific CLogP range is used to inactivate non-enveloped viruses, enhancing the inactivation effect by modifying the hydrophobic core of the virus capsid.
The composition achieves high and effective inactivation of non-enveloped viruses, including norovirus, on various surfaces without causing irritation or corrosion, suitable for diverse applications including human skin, food surfaces, and textile products.
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Abstract
Description
[Technical Field]
[0001] The present invention relates to a composition for inactivating non-enveloped viruses, a method for inactivating non-enveloped viruses, an enhancer for the non-enveloped virus inactivation effect of a cationic surfactant, and a method for enhancing the non-enveloped virus inactivation effect of a cationic surfactant. [Background technology]
[0002] Viruses can be broadly classified into enveloped and non-enveloped viruses based on their membrane structure. SARS-related viruses, such as COVID-19 (SARS-CoV-2), which causes the novel coronavirus infection that has become a global problem in recent years, and influenza viruses are classified as enveloped viruses, while noroviruses are classified as non-enveloped viruses. Enveloped viruses have a lipid membrane (envelope) on their surface and a capsid protein inside. Because they are composed of a membrane structure with a lipid membrane, they can be easily inactivated with alcohol or soap, which act on lipid membranes. Therefore, ethanol-based alcohol preparations are routinely and easily used in homes, public facilities, markets, and other places as infection control measures. However, non-enveloped viruses do not have an envelope, but as described below, their membrane is composed of capsid proteins that form a hydrophobic core. Therefore, many viruses are difficult to inactivate with ethanol or soap.
[0003] Hand and environmental hygiene is considered an important preventative measure for viral infections such as influenza and the common cold. Among these, viral acute gastroenteritis and diarrhea have not only been confirmed as outbreaks in nursing homes, schools, and hospitals, but also as food poisoning outbreaks caused by contaminated food in restaurants and food preparation facilities. These infections are caused by non-enveloped viruses such as norovirus, sapovirus, and rotavirus, which can cause severe symptoms in children and the elderly. Furthermore, the viruses that cause hand, foot, and mouth disease, a common childhood infection, and foot-and-mouth disease, which causes devastating damage to livestock, are also classified as non-enveloped viruses. Therefore, hand and environmental hygiene measures are crucial for preventing these diseases.
[0004] Norovirus, in particular, has been detected as a nonbacterial cause of food poisoning and acute gastroenteritis not only in Japan but also around the world. While bacteria such as Staphylococcus aureus and Bacillus cereus have traditionally been known to cause food poisoning, in recent years, food poisoning caused by norovirus, which causes acute gastroenteritis, has become the most common, accounting for approximately 25% of food poisoning cases and roughly half of the total number of patients. It is therefore considered a problematic virus that can cause mass infections. Oral infection via eating raw oysters and other shellfish is well-known as a common route of infection. However, there have also been numerous reports of secondary infections in homes and public facilities, where the virus is present on the hands or cooking utensils of people who have come into contact with contaminated food, in the vomit or feces of patients, or in the surrounding environment. This secondary infection, in particular, can lead to mass infections and the spread of infection, and is a major cause of an increase in the number of patients.
[0005] In order to prevent food poisoning and infection caused by norovirus, it is extremely important to implement hygiene measures such as virus removal and inactivation on floors and walls, food processing equipment, cooking utensils, etc. in mass food service facilities, restaurants, and other mass cooking facilities and kitchen spaces, as well as floors and walls, cooking utensils, furniture, textile products, etc. in homes, and floors and walls, equipment, medical equipment, etc. in public facilities, and it is desirable that these measures be implemented easily and with consideration for people and the environment.
[0006] Norovirus is a non-enveloped RNA virus classified in the Caliciviridae family and Norovirus genus. It is known to be highly resistant to acid (gastric acid) and to be infectious with only a small number (around 10 to 100 viruses). Currently, there are no vaccines or therapeutic drugs for norovirus. The only way to prevent norovirus infection is to remove or inactivate the virus by washing and disinfecting food, cooking utensils, and hands, which may be the source of the infection. However, as mentioned above, norovirus is a non-enveloped virus, and its membrane structure makes it highly physicochemically resistant. Therefore, disinfectants containing ethanol or cationic surfactants, which are effective against many bacteria, may not be sufficiently effective against norovirus when used in a typical manner. Therefore, disinfectants such as chlorine bleach (e.g., sodium hypochlorite), iodine (e.g., povidone-iodine), aldehydes (e.g., glutaraldehyde), and peracetic acid preparations are used to inactivate norovirus. However, these disinfectants are highly irritating to humans and corrode metals, requiring appropriate use. Furthermore, chlorine bleach and other disinfectants have the effect of bleaching the color and pattern of textiles, limiting their use on textile products and clothing. Therefore, in consideration of the safety of the user, the objects and situations in which they are used, there are limitations on the use of these agents on the living environment, hands, cooking utensils, clothing, etc.
[0007] For the inactivation of non-enveloped viruses, we have not yet established an antiviral preparation that can be used in the same way as ethanol, which is used to inactivate enveloped viruses. If a highly infectious, high-mortality non-enveloped virus emerges in the near future, we will lack the simple yet effective hygiene measures available for inactivating influenza and coronaviruses. While hypochlorite aqueous solution exhibits excellent inactivation capabilities even against non-enveloped viruses, due to its strong oxidizing power, caution is required when handling it, given its effects on the human body. Bleach also presents a corrosion problem for metals, etc.
[0008] In recent years, there has been a demand for a method for inactivating viruses that is less irritating and corrosive and can be used on textile products. For example, Patent Document 1 discloses a technology for a virus inactivating composition containing an amine compound, a cationic surfactant, and a lower alcohol. Furthermore, Patent Document 2 discloses a technology relating to an antiviral composition containing a cationic surfactant and benzyl alcohol. Meanwhile, Patent Document 3 describes that a composition containing a cationic surfactant and an aliphatic alcohol such as pentanol is effective in killing bacteria that cause pink stains, such as bacteria of the genus Methylobacterium. Also, Patent Document 4 discloses a technology that contains a cationic surfactant, an amine compound, and an organic solvent with a specific logP value, which is effective in killing bacteria that cause damp odors during laundry. [Prior art documents] [Patent documents]
[0009] [Patent Document 1] Patent No. 6936536 [Patent Document 2] Japanese Patent Application Laid-Open No. 2013-40167 [Patent Document 3] Japanese Patent Application Laid-Open No. 2012-36179 [Patent Document 4] Japanese Patent Application Laid-Open No. 2009-73915 Summary of the Invention [Problem to be solved by the invention]
[0010] However, these technologies are required to further improve the virus inactivation effect. Furthermore, because bacteria and viruses have completely different properties, it is impossible to imagine, based on Patent Documents 3 and 4, that a composition containing a specific solvent and a cationic surfactant has a high inactivation effect on non-enveloped viruses. The present invention provides a composition for inactivating non-enveloped viruses and a method for inactivating non-enveloped viruses, which have a high inactivation effect on non-enveloped viruses. The present invention also provides an enhancer for the non-enveloped virus inactivation effect of a cationic surfactant, which enhances the inactivation effect of a cationic surfactant on non-enveloped viruses, and a method for enhancing the non-enveloped virus inactivation effect of a cationic surfactant. [Means for solving the problem]
[0011] The present invention relates to a non-enveloped virus inactivation composition comprising (a) a cationic surfactant (hereinafter referred to as component (a)), (b) an aliphatic alcohol with a CLogP of 0.80 to 2.40 (hereinafter referred to as component (b)), and water.
[0012] The present invention also relates to a method for inactivating non-enveloped viruses, which comprises contacting the above-mentioned non-enveloped virus inactivating composition with a target surface.
[0013] The present invention also relates to (b) an agent for enhancing the non-enveloped virus inactivating effect of a cationic surfactant, which comprises an aliphatic alcohol having a CLogP of 0.80 or more and 2.40 or less.
[0014] The present invention also relates to a method for enhancing the non-enveloped virus inactivating effect of a cationic surfactant by adding (b) an aliphatic alcohol having a CLogP of 0.80 or more and 2.40 or less to a non-enveloped virus inactivating composition containing (a) a cationic surfactant. [Effects of the Invention]
[0015] The present invention provides a composition for inactivating non-enveloped viruses and a method for inactivating non-enveloped viruses, which have a high inactivation effect on non-enveloped viruses. The present invention also provides an enhancer for the non-enveloped virus inactivation effect of a cationic surfactant, which enhances the inactivation effect of a cationic surfactant on non-enveloped viruses, and a method for enhancing the non-enveloped virus inactivation effect of a cationic surfactant. DETAILED DESCRIPTION OF THE INVENTION
[0016] The reason why the non-enveloped virus inactivating composition of the present invention has such a high inactivating effect on non-enveloped viruses is not entirely clear, but is presumed to be as follows. The capsid protein of a non-enveloped virus is thought to have a hydrophobic core formed by the hydrophobic side chains folding inward. Because this hydrophobic core is not exposed to the surface, it is thought that (a) a cationic surfactant [component (a)] is unlikely to act on the hydrophobic core. Therefore, by allowing component (a) and (b) an aliphatic alcohol [component (b)] with a CLogP of 0.80 to 2.40 to coexist, component (b) modifies the hydrophobic core, making it easier for component (a) to act on the hydrophobic core, presumably resulting in the effects of the present invention. In the present invention, "non-enveloped virus inactivation" may mean killing a non-enveloped virus or eliminating the infectivity of a non-enveloped virus, and "non-enveloped virus inactivation effect" means killing a part or all of a non-enveloped virus or eliminating the infectivity, toxicity, or other activity of a non-enveloped virus.
[0017] [Non-enveloped virus inactivation composition] The non-enveloped virus inactivating composition of the present invention contains (a) a cationic surfactant [component (a)], (b) an aliphatic alcohol with a CLogP of 0.80 or more and 2.40 or less [component (b)], and water.
[0018] <Component (a)> Component (a) is a cationic surfactant. Examples of component (a) include quaternary ammonium salt surfactants. Component (a) may be one or more selected from cationic surfactants. The quaternary ammonium salt surfactant of the component (a) is preferably at least one selected from the compounds represented by the following general formula (a1) and the compounds represented by the following general formula (a2).
[0019] [ka]
[0020] [In the formula, R 1a is an aliphatic hydrocarbon group having 8 to 18 carbon atoms, and R 2a is a group selected from an aliphatic hydrocarbon group having from 8 to 18 carbon atoms, an alkyl group having from 1 to 3 carbon atoms, and a hydroxyalkyl group having from 1 to 3 carbon atoms, and R 3a and R 4a are each independently a group selected from an alkyl group having 1 to 3 carbon atoms and a hydroxyalkyl group having 1 to 3 carbon atoms, and X - is an anion.
[0021] [ka]
[0022] [In the formula, R 5a is an aliphatic hydrocarbon group having 8 to 18 carbon atoms, and R 6a and R 7a are each independently a group selected from an alkyl group having 1 to 3 carbon atoms and a hydroxyalkyl group having 1 to 3 carbon atoms, and X - is an anion.
[0023] In general formula (a1), R 1aFrom the viewpoint of the non-enveloped virus inactivation effect, the number of carbon atoms in R is preferably 9 or more, more preferably 10 or more, even more preferably 12 or more, and preferably 16 or less, more preferably 14 or less. 1a is preferably an alkyl group or an alkenyl group, and is preferably an alkyl group. In general formula (a1), R 2a is a group selected from aliphatic hydrocarbon groups having 8 to 18 carbon atoms, alkyl groups having 1 to 3 carbon atoms, and hydroxyalkyl groups having 1 to 3 carbon atoms. R 2a is an aliphatic hydrocarbon group having 8 to 18 carbon atoms, R 2a From the viewpoint of the non-enveloped virus inactivation effect, is preferably an alkyl or alkenyl group having 8 or more carbon atoms, more preferably 10 or more carbon atoms, and preferably 16 or less, more preferably 14 or less, and even more preferably 12 or less carbon atoms, and an alkyl group is preferred. R 2a is an alkyl group having 1 to 3 carbon atoms, R 2a R can be a methyl group, an ethyl group, or a propyl group. 2a is a group selected from hydroxyalkyl groups having 1 to 3 carbon atoms, R 2a Examples of the alkyl group include a hydroxymethyl group, a hydroxyethyl group, and a hydroxypropyl group.
[0024] In general formula (a1), R 3a and R 4a are each independently a group selected from an alkyl group having 1 to 3 carbon atoms and a hydroxyalkyl group having 1 to 3 carbon atoms. 3a and R 4a are preferably each independently a group selected from alkyl groups having 1 to 3 carbon atoms. Examples of alkyl groups having 1 to 3 carbon atoms include a methyl group, an ethyl group, and a propyl group. Examples of hydroxyalkyl groups having 1 to 3 carbon atoms include a hydroxymethyl group, a hydroxyethyl group, and a hydroxypropyl group.
[0025] In general formula (a1), X -is an anion. Examples of anions include halogen ions such as chloride, bromide, and iodide. Also included are alkyl sulfate ions having 1 to 3 carbon atoms such as methyl sulfate, ethyl sulfate, and propyl sulfate.
[0026] Preferred compounds of the general formula (a1) include one or more selected from N-alkyl-N,N,N-trimethylammonium salts in which the alkyl group has 12 or more and 18 or less carbon atoms, N,N-dialkyl-N,N-dimethyl-ammonium salts in which the alkyl group has 8 or more and 16 or less carbon atoms, and N-alkyl-N,N-dimethyl-N-ethylammonium salts in which the alkyl group has 12 or more and 16 or less carbon atoms.
[0027] In general formula (a2), R 5a is an aliphatic hydrocarbon group having 8 to 18 carbon atoms. 5a From the viewpoint of the non-enveloped virus inactivation effect, the number of carbon atoms in R is preferably 8 or more, more preferably 12 or more, and preferably 18 or less, more preferably 16 or less, and even more preferably 14 or less. 5a is preferably an alkyl group or an alkenyl group, and is preferably an alkyl group.
[0028] In general formula (a2), R 6a and R 7a are each independently a group selected from an alkyl group having 1 to 3 carbon atoms and a hydroxyalkyl group having 1 to 3 carbon atoms. 6a and R 7a are preferably each independently a group selected from alkyl groups having 1 to 3 carbon atoms. Examples of alkyl groups having 1 to 3 carbon atoms include a methyl group, an ethyl group, and a propyl group. Examples of hydroxyalkyl groups having 1 to 3 carbon atoms include a hydroxymethyl group, a hydroxyethyl group, and a hydroxypropyl group.
[0029] In general formula (a2), X -is an anion. Examples of anions include halogen ions such as chloride, bromide, and iodide. Examples of anions also include alkyl sulfate ions having 1 to 3 carbon atoms such as methyl sulfate, ethyl sulfate, and propyl sulfate.
[0030] Specific examples of the compound of general formula (a2) include N-dodecyl-N,N-dimethyl-N-benzyl ammonium salt, N-tridecyl-N,N-dimethyl-N-benzyl ammonium salt, N-tetradecyl-N,N-dimethyl-N-benzyl ammonium salt, N-pentadecyl-N,N-dimethyl-N-benzyl ammonium salt, N-hexadecyl-N,N-dimethyl-N-benzyl ammonium salt, N-dodecyl-N,N-diethyl-N-benzyl ammonium salt, N-tridecyl-N,N-diethyl-N-benzyl ammonium salt, N-tetradecyl-N,N-diethyl-N-benzyl ammonium salt, and N-hexadecyl-N,N-diethyl-N-benzylammonium salt, N-dodecyl-N-methyl-N-ethyl-N-benzylammonium salt, N-tridecyl-N-methyl-N-ethyl-N-benzylammonium salt, N-tetradecyl-N-methyl-N-ethyl-N-benzylammonium salt, N-pentadecyl-N-methyl-N-ethyl-N-benzylammonium salt, and N-hexadecyl-N-methyl-N-ethyl-N-benzylammonium salt.
[0031] Component (a) is preferably a quaternary ammonium salt surfactant having one or two alkyl groups having from 8 to 16 carbon atoms, and the remainder being groups selected from an alkyl group having from 1 to 3 carbon atoms, a hydroxyalkyl group having from 1 to 3 carbon atoms, and a benzyl group. For example, component (a) is represented by general formula (a1), R 1a is an alkyl group having 8 to 16 carbon atoms, and R 2a is a group selected from an alkyl group having 8 to 16 carbon atoms, an alkyl group having 1 to 3 carbon atoms, and a hydroxyalkyl group having 1 to 3 carbon atoms, and R 3aand R 4a are each independently a group selected from an alkyl group having 1 to 3 carbon atoms and a hydroxyalkyl group having 1 to 3 carbon atoms, and X - is an anion, and compounds of general formula (a2), 5a is an alkyl group having 8 to 16 carbon atoms, and R 6a and R 7a are each independently a group selected from an alkyl group having 1 to 3 carbon atoms and a hydroxyalkyl group having 1 to 3 carbon atoms, and X - is an anion.
[0032] <(b) Component> Component (b) is an aliphatic alcohol with a CLogP of 0.80 or more and 2.40 or less. Component (b) acts on the capsid protein that forms the hydrophobic core on the surface of non-enveloped viruses, and is an important component for loosening the rigid structure. By using component (b) in combination with component (a), component (a) acts more predominantly on non-enveloped viruses. Component (b) may be one or more selected from the above-mentioned aliphatic alcohols. The aliphatic alcohol of component (b) may be a chain saturated alcohol, a chain unsaturated alcohol, or an alicyclic alcohol, and from the viewpoint of the non-enveloped virus inactivation effect, a chain saturated alcohol is preferred. Furthermore, the aliphatic alcohol of component (b) may be either a straight-chain or branched-chain alcohol. From the viewpoint of non-enveloped virus inactivation effect, the number of carbon atoms in component (b) is preferably 4 or more, more preferably 5 or more, and preferably 8 or less, more preferably 7 or less, and even more preferably 6 or less. When component (b) is a chain saturated alcohol, the CLogP of component (b) is 0.80 or more and 2.40 or less, preferably 2.00 or less, more preferably 1.80 or less, and even more preferably 1.60 or less, from the viewpoint of the non-enveloped virus inactivation effect. Furthermore, when component (b) is an alicyclic alcohol, the CLogP of component (b) is, from the viewpoint of the non-enveloped virus inactivation effect, 0.80 or more, preferably 1.00 or more, more preferably 1.20 or more, even more preferably 1.50 or more, and 2.40 or less, preferably 2.00 or less. Component (b) may be a monohydric aliphatic alcohol or a polyhydric aliphatic alcohol, and from the viewpoint of the effect of inactivating non-enveloped viruses, a monohydric aliphatic alcohol is preferred.
[0033] From the viewpoint of non-enveloped virus inactivation effect, component (b) is preferably one or more selected from monohydric chain alcohols and monohydric alicyclic alcohols having from 4 to 8 carbon atoms.
[0034] Specific examples of component (b) include the following aliphatic alcohols (the numbers in parentheses are ClogP values): 1-butanol (0.823), 1-pentanol (1.352), 2-pentanol (1.123), 3-pentanol (1.132), 3-methyl-1-butanol (1.222), 3-methyl-2-butanol (1.002), 2,2-dimethyl-1-propanol (1.092), 1-hexanol (1.881), 2-hexanol (1.661), 3-hexanol (1.751), 2-methyl-1-butanol (1.881), 2-methyl-2-butanol (1.661), 3-methyl-2-butanol (1.751), 2-methyl-1-butanol (1.881), 2-methyl-2-butanol (1.661), 2-methyl-2-butanol (1.751), 2-methyl-2 ... Examples of suitable alcohols include one or more selected from the group consisting of 1-pentanol, 2,2-dimethyl-1-propanol, and 3-methyl-1-butanol. Examples of suitable alcohols include 1-methylcyclohexanol (1.786), 3-methylcyclohexanol (1.786), 4-methylcyclohexanol (1.786), and 4-ethylcyclohexanol (2.351). From the viewpoint of the effect of inactivating non-enveloped viruses, one or more selected from the group consisting of 1-pentanol, 2,2-dimethyl-1-propanol, and 3-methyl-1-butanol are preferred.
[0035] CLogP is an estimated value of the affinity of an organic compound for water and 1-octanol [P = (concentration of the organic compound in the 1-octanol phase) / (concentration of the organic compound in the aqueous phase)], and can be calculated using a calculation program that uses fragment values of atomic groups determined by the number of atoms constituting the compound molecule and the type of chemical bond. In the present invention, CLogP calculated using ChemDraw ver. 18.2 from PerkinElmer is used.
[0036] The non-enveloped virus inactivating composition of the present invention contains water. The water is used in an amount that makes up the remainder of the composition. For example, ion-exchanged water or distilled water can be used as the water.
[0037] <Composition and other ingredients> The non-enveloped virus inactivating composition of the present invention contains component (a) in an amount of preferably 10 ppm or more, more preferably 100 ppm or more, even more preferably 250 ppm or more, and even more preferably 500 ppm or more from the viewpoint of non-enveloped virus inactivation effect, and preferably 10,000 ppm or less, more preferably 5,000 ppm or less, even more preferably 2,000 ppm or less, and even more preferably 1,000 ppm or less from the viewpoint of economy. In the present invention, ppm refers to the mass ratio (parts per million) of each component contained in the composition (the same applies hereinafter). A non-enveloped virus inactivating composition containing component (a) in the above range can be suitably used as a composition that acts on non-enveloped viruses without dilution. In the present invention, the mass of component (a) is defined as a value converted to chloride. Alternatively, the non-enveloped virus inactivating composition may be concentrated in advance and then diluted so that the content of component (a) in the non-enveloped virus inactivating composition at the time of use falls within the above-mentioned range before application to non-enveloped viruses.
[0038] In the non-enveloped virus inactivating composition of the present invention, the content of component (b) is preferably 50% by mass or more, more preferably 60% by mass or more, even more preferably 70% by mass or more, and even more preferably 80% by mass or more, relative to the limit amount of component (b) contained in the non-enveloped virus inactivating composition that can be dissolved in water (20°C) [the content of component (b) in a saturated solution of component (b)], from the viewpoint of non-enveloped virus inactivating effect; and from the viewpoint of formulation stability, it is preferably 100% by mass or less, more preferably 95% by mass or less. A non-enveloped virus inactivating composition having a component (b) content within the above range can be suitably used as a composition that acts on non-enveloped viruses without dilution. Alternatively, the non-enveloped virus inactivating composition may be concentrated in advance and then diluted so that the content of component (b) in the non-enveloped virus inactivating composition at the time of use falls within the above-mentioned range before application to non-enveloped viruses.
[0039] That is, in the non-enveloped virus inactivating composition of the present invention, the content of component (b) per 100 g of water contained in the non-enveloped virus inactivating composition is, from the viewpoint of non-enveloped virus inactivation effect, preferably 50% by mass or more, more preferably 60% by mass or more, even more preferably 70% by mass or more, and even more preferably 80% by mass or more, relative to the solubility of component (b) in water (20°C), and from the viewpoint of blend stability, is preferably 100% by mass or less, more preferably 95% by mass or less. A non-enveloped virus inactivating composition having a component (b) content within the above range can be suitably used as a composition that acts on non-enveloped viruses without dilution. The solubility of component (b) in water (20°C) is the maximum amount (g) of component (b) that can be dissolved in 100 g of water at 20°C.
[0040] In the non-enveloped virus inactivating composition of the present invention, the mass ratio (a) / (b) of the content of component (a) to the content of component (b) is preferably 0.0001 or more, more preferably 0.0008 or more, even more preferably 0.0010 or more, and preferably 10 or less, more preferably 1 or less, even more preferably 0.1 or less, and even more preferably 0.05 or less, from the viewpoint of the non-enveloped virus inactivating effect.
[0041] From the viewpoint of the non-enveloped virus inactivating effect, the non-enveloped virus inactivating composition of the present invention preferably contains 60% by mass or more, more preferably 80% by mass or more, even more preferably 90% by mass or more, and preferably less than 100% by mass of water. Water may be the remainder other than component (a), component (b), and the optional components described below.
[0042] <(c) component> The non-enveloped virus inactivating composition of the present invention may optionally contain (c) a surfactant (excluding component (a) [hereinafter referred to as component (c)] in terms of wettability and penetration into the target object. However, component (c) and the water-soluble organic solvent (d) described below may alter the properties of components (a) and (b) that are necessary to solve the problems of the present invention, and therefore, when blending them, it is necessary to consider the impact on the effectiveness.
[0043] Examples of the (c) component include one or more selected from (c1) anionic surfactants (hereinafter referred to as (c1) component), (c2) nonionic surfactants (hereinafter referred to as (c2) component), (c3) semi-polar surfactants (hereinafter referred to as (c3) component), and (c4) amphoteric surfactants (hereinafter referred to as (c4) component).
[0044] Examples of component (c1) include one or more selected from alkyl sulfate esters in which the alkyl group has from 8 to 22 carbon atoms, alkylbenzenesulfonic acids in which the alkyl group has from 8 to 22 carbon atoms, polyoxyalkylene alkyl ether sulfates in which the alkyl group has from 8 to 22 carbon atoms (the oxyalkylene group is an oxyalkylene group having 2 or 3 carbon atoms, preferably an oxyethylene group, and the average number of moles added of the oxyalkylene group is preferably from 0.5 to 5, more preferably from 0.5 to 3), fatty acids having from 8 to 22 carbon atoms, and salts thereof. Examples of salts of the anionic surfactant that is component (c1) include alkali metal salts such as sodium and potassium, and alkanolamine salts having from 2 to 8 carbon atoms. Alkali metal salts are preferred, sodium salts or potassium salts are more preferred, and sodium salts are even more preferred. Examples of the (c2) component include one or more selected from polyoxyalkylene alkyl ethers having an alkyl group with 8 to 22 carbon atoms (the oxyalkylene group is an oxyalkylene group with 2 or 3 carbon atoms, preferably an oxyethylene group, and the average number of moles of the oxyalkylene group added is preferably 3 to 50, more preferably 3 to 20), and alkyl glycosides having an alkyl group with 8 to 14 carbon atoms (the average degree of condensation of the sugar skeleton, such as glucose, is 1 to 5, preferably 1 to 2). The component (c3) may be an amine oxide surfactant having one or more, preferably one, alkyl group having from 8 to 22 carbon atoms. Examples of the component (c4) include sulfobetaine surfactants having one or more, preferably one, alkyl group having from 8 to 22 carbon atoms, and carbobetaine surfactants having one or more, preferably one, alkyl group having from 8 to 22 carbon atoms.
[0045] The non-enveloped virus inactivating composition of the present invention can contain component (c) to the extent that the effects of the present invention are not impaired. From the viewpoint of wettability to an object, the non-enveloped virus inactivating composition of the present invention can contain component (c) in an amount of preferably 10 ppm or more and preferably 50,000 ppm or less, more preferably 10,000 ppm or less, even more preferably 5,000 ppm or less, still more preferably 2,000 ppm or less, even more preferably 1,000 ppm or less, still more preferably 500 ppm or less, and still more preferably 100 ppm or less. From the viewpoint of non-enveloped virus inactivation effect, it is preferable that the non-enveloped virus inactivating composition of the present invention does not contain component (c). In the present invention, when component (c1) is used as component (c), the mass of component (c1) is defined as the value converted into the sodium salt.
[0046] Furthermore, the non-enveloped virus inactivating composition of the present invention can contain component (c2) to the extent that the effects of the present invention are not impaired. From the viewpoint of wettability to an object, the non-enveloped virus inactivating composition of the present invention can contain component (c2) in an amount of preferably 10 ppm or more and preferably 50,000 ppm or less, more preferably 10,000 ppm or less, even more preferably 5,000 ppm or less, still more preferably 2,000 ppm or less, even more preferably 1,000 ppm or less, still more preferably 500 ppm or less, and still more preferably 100 ppm or less. From the viewpoint of non-enveloped virus inactivating effect, it is preferable that the non-enveloped virus inactivating composition of the present invention does not contain component (c2).
[0047] As described above, the non-enveloped virus inactivating composition of the present invention preferably contains component (c) in an amount of 10 ppm or more, and preferably 50,000 ppm or less, more preferably 10,000 ppm or less, even more preferably 5,000 ppm or less, even more preferably 2,000 ppm or less, even more preferably 1,000 ppm or less, even more preferably 500 ppm or less, and even more preferably 100 ppm or less, as a whole. From the viewpoint of non-enveloped virus inactivation efficacy, the non-enveloped virus inactivating composition of the present invention preferably does not contain component (c). Note that component (c) may be carried over from other components into the non-enveloped virus inactivating composition of the present invention. However, if the amount carried over is so small as to not reach the aforementioned concentration, the non-enveloped virus inactivating composition of the present invention may not contain component (c).
[0048] In the non-enveloped virus inactivating composition of the present invention, the content of component (a) relative to the total content of surfactants contained in the composition may be, from the viewpoint of non-enveloped virus inactivation effect, preferably 40% by mass or more, more preferably 60% by mass or more, even more preferably 80% by mass or more, still more preferably 90% by mass or more, even more preferably 95% by mass or more, and preferably 100% by mass or less. The total content of surfactants contained in the non-enveloped virus inactivating composition of the present invention may be the combined content of component (a) and component (c).
[0049] <(d) component> The non-enveloped virus inactivating composition of the present invention may optionally contain (d) a water-soluble organic solvent (excluding component (b)) [hereinafter referred to as component (d)] in terms of wettability and permeability to the target object. The water-soluble organic solvent of the present invention is one that dissolves 20 g or more in 100 g of deionized water at 20°C.
[0050] Component (d) is a water-soluble organic solvent other than the aliphatic alcohol of component (b) having a ClogP of 0.80 to 2.40, and examples thereof include water-soluble organic solvents having a ClogP outside the range of 0.80 to 2.40, and which may contain an ether bond and include one or more water-soluble organic solvents selected from hydrocarbon compounds having 2 or more carbon atoms, preferably 3 or more carbon atoms, and 12 or less carbon atoms, preferably 10 or less carbon atoms, and having a hydroxy group. Component (d) can be further classified into the following categories (d1) to (d4). Examples of the alkylene glycol include one or more selected from (d1) polyhydric alcohols having 2 to 4 carbon atoms, (d2) di- or trialkylene glycols having 2 to 4 carbon atoms in the alkylene glycol unit, (d3) monoalkoxy (preferably methoxy, ethoxy, propoxy, or butoxy) ethers, phenoxy ethers, or benzooxy ethers of di- or tetraalkylene glycols having 2 to 4 carbon atoms in the alkylene glycol unit, and (d4) monohydric alcohols having 1 to 3 carbon atoms.
[0051] Examples of component (d) include water-soluble organic solvents other than component (b) having 2 or more carbon atoms, preferably 3 or more carbon atoms, and 10 or less carbon atoms, preferably 8 or less carbon atoms. Specifically, (d1) includes ethylene glycol, propylene glycol, glycerin, and isoprene glycol; (d2) includes diethylene glycol and dipropylene glycol; (d3) includes propylene glycol monomethyl ether, propylene glycol monoethyl ether, diethylene glycol monobutyl ether (also known as butyl diglycol), phenoxyethanol, phenoxytriethylene glycol, and phenoxyisopropanol; and (d4) includes monohydric alcohols having 1 to 3 carbon atoms, and these may be used alone or in combination. Component (d) is preferably one or more water-soluble organic solvents selected from propylene glycol, dipropylene glycol, diethylene glycol monobutyl ether, phenoxyethanol, phenyl glycol, phenoxyisopropanol, and propanol. Component (d) preferably contains an alkoxy group, and diethylene glycol monobutyl ether is more preferred.
[0052] In the non-enveloped virus inactivating composition of the present invention, component (d) may alter the properties of components (a) and (b) in the composition. Therefore, like component (c), it is preferable to limit the amount of component (d). However, if formulation stability needs to be considered from a product perspective, component (d) can be included to the extent that does not significantly impair the effects of the present invention. The content of component (d) in the non-enveloped virus inactivating composition of the present invention is preferably 30% by mass or less, more preferably 20% by mass or less, even more preferably 10% by mass or less, even more preferably 5% by mass or less, even more preferably 1% by mass or less, and even more preferably 0.1% by mass or less. From the viewpoint of non-enveloped virus inactivation effect, the non-enveloped virus inactivating composition of the present invention preferably does not contain component (d). However, if component (d) needs to be included, component (d) may be included preferably at least 0.01% by mass, more preferably at least 0.1% by mass, although the content of component (d) should be less than the content of component (b).
[0053] In the present invention, use of component (d) may impair the effect of component (b), and therefore, from the viewpoint of non-enveloped virus inactivation effect, the mass ratio (d) / (b) of the content of component (d) to the content of component (b) contained in the non-enveloped virus inactivation composition is preferably 0 or more and preferably 1 or less, more preferably less than 1, even more preferably 0.1 or less, and still more preferably 0.01 or less. From the viewpoint of non-enveloped virus inactivation effect, it is particularly preferable that the non-enveloped virus inactivation composition of the present invention does not contain component (d), and it is preferable that the mass ratio (d) / (b) is 0.
[0054] The non-enveloped virus inactivating composition of the present invention may optionally contain a chelating agent, an antifoaming agent, a stabilizer, a pH adjuster, a dye, a fragrance, or a preservative, as long as the effects of the present invention are not impaired.
[0055] The viruses targeted by the non-enveloped virus inactivation composition of the present invention are non-enveloped viruses, such as non-enveloped viruses that have capsid proteins on their surface that are difficult to inactivate with ethanol, and further include non-enveloped viruses belonging to the Norovirus genus. Non-enveloped viruses may be, for example, single-stranded (+) RNA viruses, single-stranded (-) RNA viruses, double-stranded RNA viruses, single-stranded DNA viruses, and double-stranded DNA viruses that do not have a lipid layer or lipid bilayer on the viral surface. Examples of non-enveloped viruses include viruses with DNA genomes such as adenovirus, parvovirus, papovavirus, and human papillomavirus, and viruses with RNA genomes such as rotavirus, coxsackievirus, enterovirus, sapovirus, norovirus, poliovirus, echovirus, hepatitis A virus, hepatitis E virus, rhinovirus, astrovirus, and bacteriophage MS2. Incidentally, the non-enveloped virus inactivating composition of the present invention is also effective against enveloped viruses. Enveloped viruses may be single-stranded (+)RNA viruses, single-stranded (-)RNA viruses, double-stranded RNA viruses, single-stranded DNA viruses, and double-stranded DNA viruses that have a lipid layer or lipid bilayer on the virus surface. Examples of enveloped viruses include herpesvirus, influenza virus, paramyxovirus, rabies virus, respiratory syncytial virus, coronavirus, HIV, smallpox virus, hepatitis B virus, hepatitis C virus, hepatitis D virus, rubella virus, SARS coronavirus (SARS-CoV), and MERS coronavirus (MERS-CoV). The non-enveloped virus inactivating composition of the present invention can also inactivate these enveloped viruses. The non-enveloped virus inactivating composition of the present invention has a high non-enveloped virus inactivating effect against non-enveloped viruses, and further against non-enveloped viruses belonging to the genus Norovirus.
[0056] The non-enveloped virus inactivating composition of the present invention has a high non-enveloped virus inactivating effect against non-enveloped viruses even in the pH range from acidic to alkaline. The non-enveloped virus inactivating composition of the present invention has an excellent virus inactivating effect even in the pH range from acidic to neutral, which is an effect not found in conventional non-enveloped virus inactivating compositions. The pH of the non-enveloped virus inactivating composition of the present invention at 20°C can be selected from 0 or more, further 1 or more, further 2 or more, further 3 or more, further 4 or more, and 11 or less, further 10 or less, further 9 or less, further 8 or less, further 7 or less, from the viewpoint of irritation to the skin. The pH of the present invention is measured by the glass electrode method. This pH is measured by the following measurement method.
[0057] <Measurement method of pH> A pH measurement composite electrode (e.g., a glass-ground sleeve type manufactured by Horiba, Ltd.) with a saturated potassium chloride aqueous solution (3.33 mol / L) as the pH electrode internal solution is connected to a pH meter (e.g., a pH / ion meter F-23 manufactured by Horiba, Ltd.). Next, a pH 4.01 standard solution (phthalate standard solution), a pH 6.86 standard solution (neutral phosphate standard solution), and a pH 9.18 standard solution (borate standard solution) are each filled into 100 mL beakers and immersed in a thermostatic bath at 20°C for 30 minutes. The pH measurement electrode is immersed in the thermostatically adjusted standard solutions for 3 minutes, and calibration is performed in the order of pH 6.86 → pH 9.18 → pH 4.01. The non-enveloped virus inactivating composition to be measured is adjusted to 20°C, and the electrode of the pH meter is immersed in the sample. The pH is measured after 1 minute.
[0058] The non-enveloped virus inactivating composition of the present invention can be used in the form of, for example, a liquid, a gel, or a paste. Depending on the form of use, the non-enveloped virus inactivating composition of the present invention can contain, as appropriate, a solubilizing carrier such as water or a solvent, a gelling agent, or the like.
[0059] The non-enveloped virus inactivating composition of the present invention can be used for (1) the body, for example, on human skin, fingers, hair, and the oral cavity; (2) food, for example, on the surface of food materials such as vegetables; (3) hard articles; (4) textile products, for example, textile materials such as cloth and thread, and products made therefrom; and (5) livestock, for example, cows, pigs, and birds. Examples of hard articles include hard articles with hard surfaces, such as bathrooms, toilets, kitchens, floors, doorknobs, tableware, food processing equipment, desks, chairs, and walls. These hard articles may be used in homes or in public facilities and factories, such as swimming pools, bathhouses, cafeterias, hospitals, and livestock facilities. The non-enveloped virus inactivating composition of the present invention may be used on hard surfaces.
[0060] <Method for inactivating non-enveloped viruses> The present invention provides a method for inactivating non-enveloped viruses, which comprises contacting a target surface with the non-enveloped virus inactivating composition of the present invention. In the method for inactivating non-enveloped viruses of the present invention, the aspects described for the non-enveloped virus inactivating composition of the present invention can be appropriately applied to the non-enveloped virus inactivating composition to be brought into contact with a target surface.
[0061] The target surfaces of the non-enveloped virus inactivation method of the present invention can be (1) the body, such as human skin, fingers, hair, and the inside of the mouth; (2) food, such as the surface of food materials such as vegetables; (3) hard objects; (4) textile products, such as textile materials such as cloth and thread, and products made therefrom; and (5) livestock, such as cows, pigs, and birds. Examples of hard objects include hard objects with hard surfaces, such as bathrooms, toilets, kitchens, floors, doorknobs, tableware, food processing equipment, desks, chairs, and walls. These hard objects may be used in homes or in public facilities and factories, such as swimming pools, bathhouses, cafeterias, hospitals, and livestock facilities. The target surfaces of the non-enveloped virus inactivation method of the present invention may be hard surfaces.
[0062] In the method for inactivating non-enveloped viruses of the present invention, a concentrated composition containing components (a) and (b) of the present invention may be prepared in advance, and the concentrated composition may be diluted with water to prepare the non-enveloped virus inactivating composition of the present invention, which may then be brought into contact with the target surface. That is, the method for inactivating non-enveloped viruses of the present invention may also be a method for inactivating non-enveloped viruses in which a concentrated composition containing components (a) and (b) of the present invention is diluted with water to prepare the non-enveloped virus inactivating composition of the present invention, and the non-enveloped virus inactivating composition is brought into contact with the target surface without dilution.
[0063] Methods for contacting the non-enveloped virus inactivating composition of the present invention with a target surface include contacting the non-enveloped virus inactivating composition of the present invention with a target surface on which a non-enveloped virus is present or is thought to be present. Methods for contacting the non-enveloped virus inactivating composition with a target surface include spraying or applying the composition, and immersing the target surface, such as a textile product, in the non-enveloped virus inactivating composition of the present invention. Alternatively, the non-enveloped virus inactivating composition of the present invention may be impregnated into a nonwoven fabric and then contacted with the target surface.
[0064] When the non-enveloped virus inactivating composition of the present invention is sprayed or applied to a target surface, the non-enveloped virus inactivating composition of the present invention can be filled into a container equipped with a sprayer and sprayed in the form of droplets or foam, or the non-enveloped virus inactivating composition of the present invention can be poured from the container onto the target surface and applied with a brush or the like. Examples of containers equipped with a sprayer include manual spray devices that do not use a propellant, such as trigger-type spray containers and pump-type spray containers, and aerosols that use a propellant. The container equipped with the sprayer is preferably a trigger-type sprayer that can spray the contents in the form of droplets or foam, and more preferably a trigger-type sprayer equipped with a mechanism for spraying the contents in the form of droplets or a trigger-type sprayer equipped with a mechanism for forming foam (foam-forming mechanism).
[0065] When a target surface, such as a textile product, is immersed in the non-enveloped virus inactivating composition of the present invention, the target surface and the non-enveloped virus inactivating composition of the present invention may be left to stand during immersion or may be stirred. When stirring the non-enveloped virus inactivating composition of the present invention, stirring may be performed by hand or using a rotary stirrer. A rotary stirrer is an instrument that stirs the target surface and the non-enveloped virus inactivating composition of the present invention by rotating them around a certain axis of rotation. A rotary stirrer may stir in one direction only or in the opposite direction. Furthermore, stirring can be performed continuously or intermittently. Examples of rotary stirrers available to users include pulsator-type washing machines, agitator-type washing machines, and drum-type washing machines.
[0066] When the non-enveloped virus inactivating composition of the present invention is impregnated into a nonwoven fabric and brought into contact with a target surface, the nonwoven fabric may be processed into a sheet, and the fibers constituting the nonwoven fabric are preferably composed of one or more types of fibers selected from hydrophilic fibers and hydrophobic fibers. In the present invention, hydrophilic fibers refer to fibers having a moisture regain under standard conditions (20°C, 65% RH) of more than 5% by mass. The moisture regain under standard conditions is measured by the method specified in JIS L 1013 and JIS L 1015. Hydrophobic fibers refer to fibers having a moisture regain under standard conditions (20°C, 65% RH) of 5% by mass or less. The method for contacting the non-enveloped virus inactivating composition of the present invention with the target surface can be any of rubbing, kneading, and tapping, by pressing the non-woven fabric impregnated with the non-enveloped virus inactivating composition of the present invention against the target surface and applying an external force within a range that does not damage the target object.
[0067] From the viewpoint of the non-enveloped virus inactivation effect, the time for which the non-enveloped virus inactivating composition of the present invention is brought into contact with the target surface (time for which it is left standing) is preferably 30 seconds or more, more preferably 1 minute or more, even more preferably 5 minutes or more, and preferably 120 minutes or less, more preferably 60 minutes or less, even more preferably 10 minutes or less. After contact, you can let it dry, wipe it off with a clean cloth, or rinse it with water. When rinsing, you can apply external force (physical force) with a sponge or simply rinse it with running water.
[0068] <An enhancer of cationic surfactants' inactivation effect on non-enveloped viruses> The present invention provides an agent for enhancing the non-enveloped virus inactivation effect of a cationic surfactant, which comprises (b) an aliphatic alcohol having a CLogP of 0.80 or more and 2.40 or less [hereinafter referred to as component (b)]. As the component (b) in the agent for enhancing the non-enveloped virus inactivation effect of a cationic surfactant of the present invention, the aspects of the component (b) described in the non-enveloped virus inactivation composition of the present invention can be appropriately applied. Furthermore, the non-enveloped virus inactivation effect enhancer of a cationic surfactant of the present invention may be an enhancer of the non-enveloped virus inactivation effect of a cationic surfactant that enhances the non-enveloped virus inactivation effect of the cationic surfactant described as component (a) in the non-enveloped virus inactivation composition of the present invention. Furthermore, the non-enveloped virus inactivation effect enhancer of a cationic surfactant of the present invention may be, for example, an enhancer of a non-enveloped virus inactivation effect of a cationic surfactant that is used in a composition containing component (a) in the amount described for the non-enveloped virus inactivation composition of the present invention, and that enhances the non-enveloped virus inactivation effect of component (a) contained in the composition. Furthermore, although the viruses to be inactivated by component (a) are non-enveloped viruses as described in the non-enveloped virus inactivating composition of the present invention, the non-enveloped virus inactivating composition of the present invention can also inactivate enveloped viruses. Therefore, the non-enveloped virus inactivation effect enhancer of a cationic surfactant of the present invention may be an enhancer of the virus inactivation effect of a cationic surfactant.
[0069] The enhancer of the non-enveloped virus inactivation effect of a cationic surfactant of the present invention can contain component (b) in an amount of preferably 0.1% by mass or more, more preferably 0.5% by mass or more, and even more preferably 1.0% by mass or more, from the viewpoint of non-enveloped virus inactivation effect, and preferably 100% by mass or less, more preferably 50% by mass or less, and even more preferably 20% by mass or less, from the viewpoint of formulation stability. The enhancer of the non-enveloped virus inactivation effect of a cationic surfactant of the present invention may be a composition consisting of component (b).
[0070] Furthermore, from the viewpoint of non-enveloped virus inactivation effect, the cationic surfactant non-enveloped virus inactivation effect enhancer of the present invention can be used for component (a) or a composition containing component (a) so that the mass ratio (a) / (b) of component (a) to component (b) is preferably 0.0001 or more, more preferably 0.0008 or more, even more preferably 0.0010 or more, and preferably 10 or less, more preferably 1 or less, even more preferably 0.1 or less, and even more preferably 0.05 or less.
[0071] Furthermore, in a mixture containing component (a), component (b), and water obtained by mixing the cationic surfactant non-enveloped virus inactivation effect enhancer of the present invention with a composition containing component (a), the content of component (b) can be mixed with a composition containing component (a) so that, from the viewpoint of non-enveloped virus inactivation effect, the content of component (b) is preferably 50% by mass or more, more preferably 60% by mass or more, even more preferably 70% by mass or more, even more preferably 80% by mass or more, and preferably 100% by mass or less, more preferably 95% by mass or less, relative to the limit amount of component (b) that can be dissolved in water (20°C) contained in the mixture (the content of component (b) in a saturated solution of component (b)).
[0072] That is, in a mixture containing component (a), component (b), and water obtained by mixing the cationic surfactant non-enveloped virus inactivation effect enhancer of the present invention with a composition containing component (a), the content of component (b) per 100 g of water contained in the mixture can be mixed with a composition containing component (a) so that, from the viewpoint of non-enveloped virus inactivation effect, the content of component (b) per 100 g of water contained in the mixture is preferably 50% by mass or more, more preferably 60% by mass or more, even more preferably 70% by mass or more, even more preferably 80% by mass or more, and preferably 100% by mass or less, more preferably 95% by mass or less, relative to the solubility of component (b) in water (20°C). The solubility of component (b) in water (20°C) is the maximum amount (g) of component (b) that can be dissolved in 100 g of water at 20°C.
[0073] <Method for enhancing the non-enveloped virus inactivation effect of cationic surfactants> The present invention provides a method for enhancing the non-enveloped virus inactivating effect of a cationic surfactant by adding (b) an aliphatic alcohol [component (b)] having a CLogP of 0.80 or more and 2.40 or less to a non-enveloped virus inactivating composition containing (a) a cationic surfactant [component (a)]. In the method of enhancing the non-enveloped virus inactivating effect of the cationic surfactant of the present invention, the aspects described for the non-enveloped virus inactivating composition of the present invention can be appropriately applied as component (a) and component (b). Furthermore, the method for enhancing the non-enveloped virus inactivation effect of the cationic surfactant of the present invention may be, for example, a method for enhancing the non-enveloped virus inactivation effect of a cationic surfactant, in which the cationic surfactant is used in a composition containing component (a) in the amount described for the non-enveloped virus inactivation composition of the present invention, thereby enhancing the non-enveloped virus inactivation effect of component (a) contained in the composition. Furthermore, the method for enhancing the non-enveloped virus inactivation effect of the cationic surfactant of the present invention can be achieved by using component (b) so as to achieve the (a) / (b) mass ratio, the content of component (b) relative to the limit amount of component (b) that can be dissolved in water (20°C) contained in the non-enveloped virus inactivation composition, and the like, as described above in the description of the enhancer for the non-enveloped virus inactivation effect of a cationic surfactant of the present invention. Furthermore, the viruses to be inactivated by component (a) may be not only non-enveloped viruses as described in the non-enveloped virus inactivating composition of the present invention, but also enveloped viruses. Therefore, the method of the present invention for enhancing the non-enveloped virus inactivating effect of a cationic surfactant may be a method for enhancing the virus inactivating effect of a cationic surfactant. [Example]
[0074] <Composition ingredients> The following components were used in the examples, comparative examples and formulation examples. <Component (a)> a-1: benzalkonium chloride, Sanizol 50 (manufactured by Kao Corporation), general formula (a2), R 5a is an alkyl group having 12 to 16 carbon atoms, and R 6a and R 7a is a methyl group, and X - is a compound of chloride ions. a-2: Didecyldimethylammonium chloride (DDAC) (manufactured by Kao Corporation), general formula (a1), R 1a and R 2a is an alkyl group having 10 carbon atoms, and R 3a and R 4a is a methyl group, and X - is a compound of chloride ions.
[0075] <(b) Component> b-1: 1-butanol (0.823), manufactured by Fujifilm Wako Pure Chemical Industries, Ltd. b-2: 1-pentanol (1.352), manufactured by Tokyo Chemical Industry Co., Ltd. b-3: 2-pentanol (1.123), manufactured by Tokyo Chemical Industry Co., Ltd. b-4: 3-pentanol (1.132), manufactured by Tokyo Chemical Industry Co., Ltd. b-5: 3-methyl-1-butanol (1.222), manufactured by Tokyo Chemical Industry Co., Ltd. b-6: 3-methyl-2-butanol (1.002), manufactured by Tokyo Chemical Industry Co., Ltd. b-7: 2,2-dimethyl-1-propanol (1.092), manufactured by Tokyo Chemical Industry Co., Ltd. b-8: 1-Hexanol (1.881), manufactured by Fujifilm Wako Pure Chemical Industries, Ltd. b-9: 2-Hexanol (1.661), manufactured by Fujifilm Wako Pure Chemical Industries, Ltd. b-10: 3-Hexanol (1.751), manufactured by Fujifilm Wako Pure Chemical Industries, Ltd. b-11: 2-Methylcyclohexanol (1.786), manufactured by Tokyo Chemical Industry Co., Ltd. b-12: 3-Methylcyclohexanol (1.786), manufactured by Tokyo Chemical Industry Co., Ltd. b-13: 4-Methylcyclohexanol (1.786), manufactured by Tokyo Chemical Industry Co., Ltd. b-14: 4-Ethylcyclohexanol (2.351), manufactured by Tokyo Chemical Industry Co., Ltd. The values in parentheses for components (b) and (b') are CLogP values.
[0076] <(b') component> ·b'-1:1-propanol (0.294), Fujifilm Wako Pure Chemical Industries, Ltd. ·b'-2:2-Propanol (0.074), Fujifilm Wako Pure Chemical Industries, Ltd. ·b'-3:2-butanol (0.603), Fujifilm Wako Pure Chemical Industries, Ltd. b'-4: t-butanol (0.473) (2-methyl-2-propanol), manufactured by Fujifilm Wako Pure Chemical Industries, Ltd. ·b'-5:1-heptanol (2.410), Fujifilm Wako Pure Chemical Industries, Ltd. ·b'-6:1-octanol (2.939), Fujifilm Wako Pure Chemical Industries, Ltd.
[0077] <(c) component> c-1: Sodium dodecyl sulfate (SDS) c-2: Polyoxyethylene alkyl ether (alkyl group carbon number 12 to 14, average number of moles added 3), Softanol 30 (manufactured by Nippon Shokubai Co., Ltd.) c-3: Lauryl dimethylamine oxide, Amphitol 20N (Kao Corporation) c-4: Lauryl amide propyl betaine, Amphitol 20AB (Kao Corporation) <(d) component> d-1: Diethylene glycol monobutyl ether (butyl diglycol) d-2: 2-propanol <Other> ·SM buffer: 0.58% NaCl, 0.2% MgSO4·7H2O, 50mM Tris-HCl (pH 7.5)
[0078] Example 1 and Comparative Example 1: Bacteriophage MS2 Evaluation Method (1) Preparation of bacterial suspension Escherichia coli NBRC 13965 (provided by NBRC) was inoculated onto standard agar medium (Nissui Pharmaceutical) and cultured overnight at 37°C. 12 mL of LB medium (BD Difco LB Broth, Lennox) was dispensed into a cell culture flask, and the resulting single colony was suspended and cultured overnight with shaking at 37°C and 200 rpm. 12 mL of LB medium was dispensed into a new cell culture flask, and 100 μL of the resulting culture was added. Culture was continued at 37°C and 200 rpm until the OD600 reached 0.3, preparing a bacterial suspension for use in preparing double-plate agar medium.
[0079] (2) Preparation of double agar plates A bottom agar plate was prepared by pouring 25 mL of autoclaved LB agar medium (agar concentration 1.5% by mass) into a square Petri dish (120 × 120 × 17 mm, Greiner Japan) and allowing it to cool and harden. 4.0 mL of the bacterial solution prepared in (1) was added to 36 mL of autoclaved LB soft agar medium (agar concentration 0.6% by mass) kept at 50°C, and the mixture was stirred quickly. 15 mL of the mixture was poured onto the bottom agar plate prepared earlier to prepare a double agar plate.
[0080] (3) Contact of the non-enveloped virus inactivating composition with the non-enveloped virus 1.0 × 10 IgG suspended in SM buffer was added to each 1.5 mL plastic tube containing 990 μL of the non-enveloped virus inactivation composition shown in Tables 1 and 2. 11 Ten microliters of Escherichia coli phage MS2 NBRC 102619 (distributed by NBRC) containing pfu / mL of virion was added, stirred thoroughly, and then allowed to stand for 5 minutes to allow contact between the non-enveloped virus inactivation composition and the non-enveloped virus. Ten microliters of the mixture was added to 990 μL of neutralizing medium to terminate contact between the non-enveloped virus inactivation composition and the non-enveloped virus. The mixture was then mixed with the neutralizing medium and serially diluted (10- to 1,000,000-fold) with SM buffer to prepare samples for spot testing. A control sample was also prepared by the same procedure, using SM buffer instead of the non-enveloped virus inactivation composition.
[0081] (4) Evaluation of non-enveloped virus inactivation effect by spot test 5.0 μL of the sample prepared in (3) was spotted onto the double agar plate prepared in (2) and cultured overnight at 37°C. The dilution ratio at which death (plaques) of E. coli caused by virus infection was no longer observed was visually confirmed, and the non-enveloped virus inactivation effect of the non-enveloped virus inactivation composition was evaluated by comparing with the results of the control sample. The evaluation results of the non-enveloped virus inactivation effect are shown in Tables 1 and 2.
[0082] In Tables 1 and 2, the MS2 inactivation effect (Δlog) is defined by the following formula: MS2 inactivation effect (Δlog) = LogC - LogS C: The dilution ratio at which the death of E. coli in the control sample was no longer confirmed. S: Dilution ratio at which the death of E. coli in the test sample is no longer confirmed It can be said that the larger the value of the MS2 inactivation effect (Δlog), the higher the non-enveloped virus inactivation effect of the non-enveloped virus inactivation composition.
[0083] [Table 1]
[0084] [Table 2]
[0085] In Tables 1 and 2, the content of component (a) is expressed in parts per million (ppm) based on the non-enveloped virus inactivating composition. Furthermore, the content of component (b) is expressed as a percentage (% by mass) based on the non-enveloped virus inactivating composition. In other words, the non-enveloped virus inactivating compositions shown in Tables 1 and 2 in (3) above are compositions containing component (a) and component (b) as blended ingredients, with the remainder being water. The non-enveloped virus inactivating compositions shown in Table 3, which will be described in detail later, are similar to the non-enveloped virus inactivating compositions shown in Tables 1 and 2. Furthermore, the pH at 20°C of the non-enveloped virus inactivating compositions shown in Tables 1 to 3 is in the range of 6 or more and 8 or less. In Tables 1 to 3, the "limit amount of (b) that can be dissolved in water (20°C)" in "(b) / limit amount of (b) that can be dissolved in water (20°C)" refers to the limit amount of component (b) contained in the non-enveloped virus inactivating composition that can be dissolved in water (20°C). In the tables, "(b) / limit amount of (b) that can be dissolved in water (20°C)" indicates the ratio of the amount of component (b) in the composition to the limit amount of component (b) in mass %. In addition, in Table 2, b'-1, b'-2, and b'-4 are miscible with water in any proportion, so the "maximum amount of (b) that can be dissolved in (b) / water (20°C)" was not calculated.
[0086] The results in Tables 1 and 2 show that the non-enveloped virus inactivating composition of the example containing components (a) and (b) has a higher non-enveloped virus inactivating effect than the non-enveloped virus inactivating composition of the comparative example.
[0087] Example 2 and Comparative Example 2: Human Norovirus Evaluation Method (1) Human Intestinal Enteroid (HIE) Culture HIEs were embedded in Matrigel (Corning, 356231) and cultured in three dimensions on 48-well plates. IntestiCult Organoid Growth Medium (Human) (STEMCELL Technologies, ST-06010) was used as the medium. Medium changes, passaging, and monolayer formation using 96-well plates were performed according to the user's manual. CultureSure Y-27632 (Fujifilm Wako Pure Chemical Industries, 036-24023), a ROCK (Rho-associated coiled-coil forming kinase / Rho-binding kinase) inhibitor, was added to the medium at a final concentration of 10 μM to inhibit anoikis for two days after trypsinization. Basal medium was prepared by adding 5 mL of GlutaMAX I (100x) (Gibco, 35050-061), 5 mL of 1 M HEPES (Gibco, 15630080), and 5 mL of Penicillin-Streptomycin (Gibco, 15140122) to 500 mL of Advanced DMEM / F12 (Gibco, 12634010). Differentiation medium was prepared by mixing equal volumes of basal medium and IntestiCult Organoid Growth Medium component A. Cells were monolayered in a 96-well plate and induced to differentiate for a total of 7 days by changing the differentiation medium at 200 μL per well every 2 days.
[0088] (2) Preparation of a 10% emulsion of human norovirus (HNV)-containing feces A 10% fecal emulsion was prepared from feces of a GII.4 HNV patient. One tablet of Complete protease inhibitor cocktail tablets (Sigma-Aldrich, 11697498001) was suspended in 50 mL of D-PBS(-). 1 g of feces was suspended in 10 mL of D-PBS(-) containing Complete and mixed thoroughly using a test tube mixer. The suspension was left to stand at 4°C for 20 minutes and then centrifuged at 2000 × g for 10 minutes at 4°C. The supernatant was collected in a new tube and stored at -80°C until use in the infection experiment.
[0089] (3) HNV inactivation and infection of differentiated HIE A 10% fecal emulsion containing HNV was diluted 10-fold with differentiation medium and filtered using a 1 mL syringe and a Millex HV Filter unit (Millipore, SLHVR04NL). 5 μL of the filtered fecal solution was mixed with 45 μL of the non-enveloped virus inactivation composition shown in Table 3 in a PA microcentrifuge tube (Beckmancoulter, 357448) and allowed to come into contact with the non-enveloped virus inactivation composition for 5 minutes at 25°C. Next, 1.45 mL of FBS (fetal bovine serum; BIOWEST) inactivated at 56°C for 30 minutes was added to the fecal solution treated with the non-enveloped virus inactivation composition. The centrifuge tube was placed in a fixed-angle rotor, TLA-55 (Beckman Coulter), and ultracentrifuged using an Optima MAX-TL (Beckman Coulter) at the maximum radius of rotation (Rmax) at a centrifugal force of 186,047 × g (equivalent to 55,000 rpm) for 1.5 hours, after which the supernatant was removed. The precipitate was resuspended in 1.45 mL of FBS that had been heat-inactivated at 56°C for 30 minutes, and then ultracentrifuged under the same conditions. The supernatant was removed. The pellet was suspended in 100 μL of differentiation medium and applied to the differentiation-induced HIE wells, from which the existing medium had been removed. Incubation was carried out at 37°C for 3 hours. After washing three times with 300 μL of basal medium, 250 μL of differentiation medium supplemented with porcine bile extract (Sigma-Aldrich, B8631-100G) at a final concentration of 125 ppm was added, and the cells were cultured at 37°C and 5% CO2 until sampling. The start of the test was the time when the pellet suspension was applied to the HIE, and 10 μL of supernatant was collected 7 days after the start of the test (day 7). The collected supernatant was stored at -80°C until subjected to RT-qPCR. A sample was also cultured for 7 days using fecal solution without contact with the non-enveloped virus inactivating composition, and the supernatant was collected as a "control (untreated with non-enveloped virus inactivating composition)."
[0090] (4) RT-qPCR The HNV genome copy number in the collected supernatant was quantified, and the human norovirus inactivation effect of the non-enveloped virus inactivation composition was evaluated based on the quantified virus amount. The Norovirus Detection Kit G1 / G2 (Toyobo, FIK-273) was used to quantify the HNV genome copy number in the collected supernatant, following the protocol. PCR amplification and data collection were performed using a LightCycler 480 II (Roche). Based on the measured virus amount, the human norovirus inactivation effect of the non-enveloped virus inactivation composition was evaluated using the following three-point scale. ◎: HNV is inactivated to the lowest detectable level. ○: HNV was detected but was reduced compared to the control (not treated with the non-enveloped virus inactivating composition). ×: HNV proliferated at a rate equivalent to that of the control (not treated with the non-enveloped virus inactivating composition).
[0091] [Table 3]
[0092] Formulation examples of the non-enveloped virus inactivating composition of the present invention are shown in Table 4. The non-enveloped virus inactivating compositions of each formulation example in Table 4 have a high non-enveloped virus inactivating effect against non-enveloped viruses. The non-enveloped virus inactivating compositions shown in Table 4 contain components (a) and (b), and optionally also contain components (c) or (d), with the remainder being water. The pH of the non-enveloped virus inactivating compositions shown in Table 4 at 20°C is in the range of 6 to 8.
[0093] [Table 4]
Claims
1. A non-enveloped virus inactivation composition comprising: (a) a cationic surfactant (hereinafter referred to as component (a)); (b) an aliphatic alcohol having a CLogP of 0.80 or more and 2.40 or less (hereinafter referred to as component (b)); and water.
2. 2. The non-enveloped virus inactivating composition according to claim 1, wherein component (a) is a quaternary ammonium salt surfactant having one or two alkyl groups each having from 8 to 16 carbon atoms, and the remainder being a group selected from an alkyl group having from 1 to 3 carbon atoms, a hydroxyalkyl group having from 1 to 3 carbon atoms, and a benzyl group.
3. 2. The non-enveloped virus inactivating composition according to claim 1, wherein component (a) is one or more compounds selected from the group consisting of a compound represented by the following general formula (a1) and a compound represented by the following general formula (a2): 【Chemical 1】 [In the formula, R 1a is an aliphatic hydrocarbon group having 8 to 18 carbon atoms, and R 2a is a group selected from an aliphatic hydrocarbon group having from 8 to 18 carbon atoms, an alkyl group having from 1 to 3 carbon atoms, and a hydroxyalkyl group having from 1 to 3 carbon atoms, and R 3a and R 4a are each independently a group selected from an alkyl group having 1 to 3 carbon atoms and a hydroxyalkyl group having 1 to 3 carbon atoms, and X - is an anion. 【Chemistry 2】 [In the formula, R 5a is an aliphatic hydrocarbon group having 8 to 18 carbon atoms, and R 6a and R 7a are each independently a group selected from an alkyl group having 1 to 3 carbon atoms and a hydroxyalkyl group having 1 to 3 carbon atoms, and X - is an anion.
4. 2. The non-enveloped virus inactivating composition according to claim 1, wherein component (b) is at least one selected from the group consisting of monohydric chain alcohols and monohydric alicyclic alcohols having from 4 to 8 carbon atoms.
5. 2. The non-enveloped virus inactivating composition according to claim 1, wherein the content of component (a) is 10 ppm or more and 10,000 ppm or less.
6. 2. The non-enveloped virus inactivating composition according to claim 1, wherein the content of component (b) per 100 g of water in the non-enveloped virus inactivating composition is 50% by mass or more and 100% by mass or less of the maximum amount of component (b) that can be dissolved in 100 g of water (20°C) contained in the non-enveloped virus inactivating composition.
7. 2. The non-enveloped virus inactivating composition according to claim 1, wherein the pH of the non-enveloped virus inactivating composition at 20°C is 4 or higher and 10 or lower.
8. The non-enveloped virus inactivating composition according to claim 1, wherein the non-enveloped virus is a virus belonging to the Norovirus genus.
9. 2. The non-enveloped virus inactivating composition according to claim 1, wherein the content of the nonionic surfactant is 50,000 ppm or less.
10. A method for inactivating non-enveloped viruses, comprising contacting a target surface with the non-enveloped virus inactivating composition according to any one of claims 1 to 9.
11. (b) An agent for enhancing the non-enveloped virus inactivation effect of a cationic surfactant, comprising an aliphatic alcohol having a CLogP of 0.80 or more and 2.40 or less.
12. A method for enhancing the non-enveloped virus inactivation effect of a cationic surfactant by adding (b) an aliphatic alcohol having a CLogP of 0.80 or more and 2.40 or less to a non-enveloped virus inactivation composition containing (a) a cationic surfactant.