WO2022244531A1

WO2022244531A1 - Anti-enveloped virus neutral detergent, disinfectant composition, and method for inactivating enveloped virus

Info

Publication number: WO2022244531A1
Application number: PCT/JP2022/016612
Authority: WO
Inventors: 雅彦森岡; 大輔島岡
Original assignee: 合同会社Sth
Priority date: 2021-05-21
Filing date: 2022-03-31
Publication date: 2022-11-24

Abstract

The present invention is an anti-enveloped virus detergent characterized by containing (A) 0.0001-0.4 mass% of a quaternary ammonium salt represented by the following general formula (1) and (B) 0.003-3.0 mass% of sulfobetaine as an amphoteric surfactant, as well as (C) water as a component, the pH of the composition being 6-8 at 25℃. The present invention is thereby provided with an antiviral detergent that has little effect on the human body and has an inactivating effect against enveloped viruses, a disinfectant composition containing the same, and a method for inactivating enveloped viruses using the said detergent and composition.

Description

Anti-enveloped virus neutral detergent, disinfectant composition, and method for inactivating enveloped virus

The present invention relates to an anti-enveloped virus neutral detergent, a disinfectant composition containing the detergent, and a method for inactivating enveloped viruses using them.

Currently, the international community, including Japan, is facing a serious risk of rapid spread of infectious disease (COVID-19) caused by the new coronavirus (SARS-CoV-2), and the establishment of effective infectious disease control is an urgent task. ing.

The principles of infectious disease countermeasures are said to be (1) countermeasures against infected persons, (2) countermeasures against the source of infection, and (3) countermeasures against the infection route. However, in the event of an infectious disease caused by a new virus, many people do not have immunity, and it will take a considerable amount of time for each person to develop immunity through vaccines, etc. (3) It is important to take measures against infection routes.

As measures to reduce the risk of contact infection, (i) wash off the virus attached to the fingers with soap, (ii) disinfect the virus attached to the fingers with alcohol, etc., (iii) touch the virus attachment with the fingers. Reduce the frequency, (iv) remove the attached virus with a wipe or the like to reduce the virus concentration on the environmental surface, (v) actively inactivate the virus on the surface using a product with a virus inactivating effect, ( vi) Avoid touching mouth, nose and eyes with contaminated hands. In the following, removing the adhering virus on the route of contact infection and inactivating the virus are collectively referred to as "virus decontamination".

In such virus decontamination, virus inactivation is important in order to prevent the virus from spreading unintentionally. Therefore, various products (compositions) for inactivating enveloped viruses including SARS-CoV-2 are being investigated.

For example, quaternary ammonium compounds such as alkyldimethylbenzylammonium chloride (ADBAC) and didecyldimethylammonium chloride (DDAC) are known to be useful in a wide variety of applications, including household and industrial disinfectant formulations ( Patent document 1). On the other hand, their use in indirect food contact applications is limited to low levels due to regulations on maximum permissible use levels of these compounds. At such low levels, these quaternary ammonium compounds alone are generally not effective for their intended use.

　Benzalkonium chloride and didecyldimethylammonium chloride have been reported to have many virus inactivating effects, mainly based on US FIFRA regulatory review data (Non-Patent Documents 1 and 2).

Benzalkonium chloride was reported to be able to inactivate SARS-CoV-2 at concentrations between 0.05% and 0.09% to greater than 3.8 Log10, and didecyldimethylammonium chloride was able to inactivate SARS-CoV-2. At 0.01% for 5 minutes of contact, a 4Log10 reduction is confirmed. However, there is no description of pH (Non-Patent Document 1). The pH is an important factor, and Patent Document 2 states that the quaternary ammonium salt does not have a virus inactivating effect unless it is alkaline (pH is 11 or higher) (Patent Document 2).
As described above, quaternary ammonium salts are highly toxic to the skin and strongly irritating to the eyes, so there is concern that their use alone may affect the human body.

In addition, cetylpyridinium chloride (CPC), a quaternary pyridinium salt, reduced feline infectious peritonitis type II (FIP type II) coronavirus by 99.95% at a concentration of 0.025% for 5 minutes of exposure. has been confirmed (Patent Document 3), and is expected to have a virus-inactivating effect against SARS-CoV-2 (Non-Patent Document 3).

Quaternary ammonium compounds (salts) are cationic surfactants, but other surfactants are also being investigated for their ability to inactivate viruses.
For example, alkylamine oxide, which is an amphoteric surfactant, has a 5 log10 inactivation effect on SARS-CoV-2 at a concentration of 0.1% and a contact time of 20 seconds, and a final concentration of 0.045% concentration for 1 minute. more than 4 log 10 inactivation has been observed with the contact of . However, other amphoteric surfactants have not been reported to have an inactivating effect on novel coronaviruses and influenza viruses (Non-Patent Document 1).

Patent Document 4 describes that sulfobetaine and mixtures thereof, including alkylamine oxide, have an inactivating effect on enveloped viruses, but the inactivation of novel coronavirus is not clear. Moreover, Patent Document 4 does not describe the combined use of a quaternary ammonium salt and sulfobetaine.
Rather, it is said that the combination of a quaternary ammonium salt and a betaine-type zwitterionic surfactant may reduce the bactericidal activity of the quaternary ammonium salt due to the ionic interaction of the surfactant (Patent document 5).

As described above, many antiviral detergents (anti-enveloped virus detergents) that inactivate enveloped viruses such as SARS-CoV-2 have been investigated, but they have little effect on humans and livestock, and are non-viral. The advent of a detergent with high activation ability is desired.

Japanese Patent Application Publication No. 2012-521434 JP 2019-052118 A Japanese translation of PCT publication No. 2007-515204 Japanese Patent Publication No. 2015-525572 JP-A-11-035974

As mentioned above, there are problems in using quaternary ammonium salts alone in the human body, etc., so how to reduce the concentration of quaternary ammonium salts and reduce their effects on the human body, etc., and use them as anti-envelope virus agents. The issue was whether it was possible.

DISCLOSURE OF THE INVENTION The present invention has been made in order to solve the above-mentioned problems, and includes an antiviral cleaning agent that has little effect on the human body and has an inactivating effect against enveloped viruses, a disinfectant composition containing the same, and a disinfectant composition containing the same. An object of the present invention is to provide a method for inactivating the enveloped virus used.

In order to solve the above problems, in the present invention, the following components (A) and (B) are contained in the following proportions with respect to the entire composition, and water is contained as the (C) component, and the composition Provided is an anti-envelope virus detergent characterized by having a pH (JIS Z 8802:2011 "pH measurement method") of 6 to 8 at 25°C.
(A) a quaternary ammonium salt represented by the following general formula (1): 0.0001 to 0.4% by mass;

(In the formula, R ₁ to R ₄ are linear, branched or cyclic C1 to C18 hydrocarbon groups, R ₁ and R ₂ may together form a cyclic group, X is fluorine a halogen atom selected from an atom, a chlorine atom, a bromine atom and an iodine atom, a hydroxy group, an alkoxy group, an acyloxy group, an alkylsulfonate group, a dialkylphosphonate group, an adipate group, a methosulfate group, a bicarbonate group or a carbonate group. )
(B) Sulfobetaine as an amphoteric surfactant: 0.003 to 3.0% by mass

Such an anti-enveloped virus cleanser has little effect on the human body and has an inactivating effect against enveloped viruses.

In this case, R ₁ to R ₄ are preferably linear or branched C1 to C18 alkyl groups.

An anti-enveloped virus detergent containing such a component (A) has a higher inactivating effect on enveloped viruses.

In the anti-enveloped virus detergent, the sulfobetaine is preferably represented by the following general formula (2).

(In the formula, R ₅ to R ₇ are an optionally substituted benzyl group or an optionally branched C1 to C18 alkyl group, and R ₅ and R ₆ together may be cyclic. Y is a C1 to C5 alkylene group.However, when Y is a C3 alkylene group, a substituent may be placed at the 2-position.)

Such a component (B) has a synergistic effect with the component (A) to further enhance the inactivation effect.

In the anti-envelope virus detergent, the quaternary ammonium salt is preferably a dialkyldimethylammonium salt.

The anti-enveloped virus detergent of the present invention particularly preferably contains such component (A).

In the anti-envelope virus detergent, the sulfobetaine is preferably lauryldimethyl-2-hydroxypropyl-3-sulfobetaine.

The anti-enveloped virus detergent of the present invention particularly preferably contains such component (B).

In the anti-envelope virus cleaning agent, the target viruses are influenza virus, novel coronavirus (SARS-CoV-2) and its variants, avian influenza virus, SFTS virus (severe fever with thrombocytopenia syndrome), Ebola virus, coronavirus ( MERS, SARS), dengue, Zika, swine fever virus (CSFV), as well as ASFvirus (African swine fever).

The anti-enveloped virus detergent of the present invention has a high inactivation ability against such viruses.

In this case, the target virus is a novel coronavirus (SARS-CoV-2) and its mutants, and the component (A) is contained in a proportion of 0.0001 or more and less than 0.01% by mass based on the entire composition. is particularly preferred.

Such an anti-envelope virus detergent has a particularly high inactivation ability against the new coronavirus and its mutant strains.

The present invention also provides a disinfectant composition containing the anti-envelope virus detergent.

Such a disinfectant composition has little effect on the human body, etc., and has an inactivating effect against enveloped viruses.

The present invention also provides a method for inactivating an enveloped virus, comprising contacting the enveloped virus with the anti-enveloped virus detergent or the disinfectant composition to inactivate the enveloped virus. .

The method for inactivating enveloped viruses of the present invention has little effect on the human body and the like, and has a high ability to inactivate enveloped viruses. Efficient and sufficient virus inactivation is possible.

According to the present invention, a combination of at least two low-concentration surfactants in a neutral region (pH = 6-8) has little effect on humans and livestock, and has a high ability to inactivate enveloped viruses. Since an anti-enveloped virus detergent and disinfectant composition can be provided, it is effective in inactivating enveloped viruses such as the new coronavirus and its mutant strains, and has a very high utility value as a countermeasure against infectious diseases.

As mentioned above, there has been a demand for the development of an antiviral cleaning agent that has little effect on the human body and has an inactivating effect against enveloped viruses.

As a result of intensive studies on the above problems, the present inventors found that quaternary ammonium salts and other surfactants (amphoteric surfactants: betaine (carbobetaine, sulfobetaine, phosphobetaine), alkylglucoside, alkylamine oxide etc.) at specific concentrations are effective, and among them, sulfobetaine synergistically increases the antiviral properties of ammonium cations, and completed the present invention.

That is, the present invention contains the following components (A) and (B) in the following proportions with respect to the entire composition, water as the component (C), and the pH of the composition (JIS Z 8802: 2011 "pH measurement method") is 6 to 8 at 25°C.
(A) a quaternary ammonium salt represented by the following general formula (1): 0.0001 to 0.4% by mass;

Although the present invention will be described in detail below, the present invention is not limited to these.

<Anti-envelope virus detergent>
An object of the present invention is to provide an anti-enveloped virus detergent (anti-envelope virus neutral detergent) or a disinfectant composition. Furthermore, by using two or more kinds of surfactants as active ingredients, the diluted surfactant exhibits anti-enveloped virus activity and is environmentally friendly.

The present invention has completed the present invention of an anti-enveloped virus detergent or disinfectant composition in the neutral region as described above.
The anti-envelope virus cleansing agent of the present invention is a composition containing components (A) and (B), which will be described later, in specific proportions relative to the entire composition, and water as component (C). The composition is characterized by having a pH of 6 to 8 at 25°C. In this specification, pH refers to a value measured according to JIS Z 8802:2011 "pH measurement method", and neutral refers to a range of pH 6-8.
The anti-envelope virus detergent of the present invention further contains additives such as surfactants other than the above components (A) and (B), if necessary, in addition to the above components (A) to (C). can also Each component will be described below.

[(A) quaternary ammonium salt]
Component (A) is a quaternary ammonium salt represented by the following general formula (1).

(In the formula, R ₁ to R ₄ are linear, branched or cyclic C1 to C18 hydrocarbon groups, R ₁ and R ₂ may together form a cyclic group, X is fluorine a halogen atom selected from an atom, a chlorine atom, a bromine atom and an iodine atom, a hydroxy group, an alkoxy group, an acyloxy group, an alkylsulfonate group, a dialkylphosphonate group, an adipate group, a methosulfate group, a bicarbonate group or a carbonate group. )

In general formula (1), R ₁ to R ₄ are linear, branched or cyclic C1 to C18 hydrocarbon groups, and R ₁ and R ₂ may together form a cyclic group. The number of carbon atoms in the above hydrocarbon group is, for example, 8 or more and 15 or less for R ₁ and R ₂ , and 1 or more and 5 or less for R ₃ and R ₄ . Specific examples of the hydrocarbon group include an alkyl group, an alkenyl group such as an allyl group, an alkynyl group, and a cycloalkyl group.
"C1" and "C18" indicate that the number of carbon atoms is 1 and 18, respectively. The same applies below.

Specific examples of the C1-C18 hydrocarbon group include C1-C18 linear alkyl groups such as methyl, ethyl and propyl groups, C2-C18 linear alkenyl groups such as vinyl and allyl groups, and ethynyl groups. linear alkynyl groups such as, C3-C18 branched alkyl groups such as isopropyl group, C3-C18 branched alkenyl groups such as isopropenyl group, and C3-C18 cyclic alkyl groups such as cyclohexyl group. Preferably, R ₁ -R ₄ are linear or branched C1-C18 alkyl groups. More preferably, it is a straight-chain C1-C18 alkyl group, and particularly preferably, R ₃ and R ₄ are a methyl group or an ethyl group.

X is a halogen atom selected from a fluorine atom, a chlorine atom, a bromine atom and an iodine atom, a hydroxy group, an alkoxy group, an acyloxy group, an alkylsulfonate group, a dialkylphosphonate group, an adipate group, a methosulfate group, a bicarbonate group, or a carbonate group is. Although these groups are not particularly limited, examples of hydrocarbon groups possessed by these groups include the same groups as those described above for R ₁ to R ₄ . Since X does not participate in virus inactivation, it may be anything as long as it forms a salt.

The quaternary ammonium salt of component (A) is not particularly limited as long as it is a quaternary ammonium salt represented by the general formula (1) above, but is preferably a dialkyldimethylammonium salt, such as a didecyldimethylammonium salt. is more preferable. The dialkyldimethylammonium salt may be a mixture of two or more different dialkyldimethylammonium salts as long as the alkyl group is C1-C18. Such a dialkyldimethylammonium salt contains a DDAC analog and may be a commercial product, for example, Biocide ST-70H (manufactured by Taisho Technos), which is commercially available as a DDAC analog cationic disinfectant.
If the component (A) is a quaternary ammonium salt different from the quaternary ammonium salt represented by the general formula (1), the synergistic effect of the component (B) described later will not be exhibited, and it will be ineffective against enveloped viruses. Poor activation ability.

The concentration of component (A) is 0.0001% by mass or more and 0.4% by mass or less, preferably 0.0002 to 0.007% by mass. For novel coronavirus (SARS-CoV-2) and its mutants, it can be less than 0.01% by mass. If the concentration of component (A) is less than 0.0001% by mass, the effect of inactivating enveloped viruses is insufficient. Non-Patent Document 1 states that 0.01% by mass or more is effective for the new coronavirus (SARS-CoV-2), but the environment (temperature, pH) etc. is not clear, and in some cases it may affect the human body. is concerned about the impact of Moreover, if it exceeds 0.4 mass, the influence on a human body etc. will become large.

[(B) amphoteric surfactant]
Component (B) is sulfobetaine as an amphoteric surfactant. As used herein, sulfobetaine has a positive charge and a negative charge at non-adjacent positions in the same molecule, and no dissociable hydrogen atom is bound to the positively charged atom (cation such as quaternary ammonium structure), which is an electrically neutral compound as a whole and has a sulfonate group. Sulfobetaine can also have a quaternary ammonium structure, but it is a compound clearly different from component (A) in that it has a sulfonate group.
Although there is no report in Non-Patent Document 1 about the inactivating effect of component (B) alone against enveloped viruses, in combination with the quaternary ammonium salt of component (A), the quaternary ammonium salt enveloped virus It exhibits a synergistic effect of improving the inert effect on In the present invention, by combining the components (A) and (B), the concentration of the quaternary ammonium salt, which is problematic when used alone in the human body, is reduced, and the effect on the human body is reduced, resulting in an anti-envelope composition. It is assumed that it can be used as a virus cleaning agent.

Although the chemical structure of sulfobetaine as component (B) is not particularly limited, it is preferably represented by the following general formula (2).

R ₅ to R ₇ are an optionally substituted benzyl group or an optionally branched C1 to C18 alkyl group, and R ₅ and R ₆ together may be cyclic. Specific examples include the groups shown for R ₁ to R ₄ above. The benzyl group may be substituted with an alkyl group, an alkoxy group, a hydroxyl group, a cyano group, a halogen atom, or the like.

Y is a C1 to C5 alkylene group. However, when Y is a C3 alkylene group (trimethylene group), the 2-position may be substituted. Examples of the substituent include those shown for the benzyl group above. Specific examples of Y include a methylene group, an ethylene group, a trimethylene group, a tetramethylene group, a pentamethylene group and a 2-hydroxypropyl group.
Proper selection of R ₅ to R ₇ can adjust the balance of hydrophobicity and hydrophilicity of sulfobetaine, and proper selection of Y can adjust the distance between positive and negative charges. A desired synergistic effect (inactivation effect against enveloped viruses) can be exhibited by adjusting these according to the component (A) to be combined.

Among them, the sulfobetaine is preferably lauryldimethyl-2-hydroxypropyl-3-sulfobetaine. Such a component (B) has a synergistic effect with the component (A) to further enhance the inactivating effect. This is probably because the sulfobetaine has an appropriate hydrophobic group (lauryl group), a hydrophilic group (hydroxyl group), and an appropriate distance between positive and negative charges (C3 group).

The (B) component sulfobetaine may be a commercially available product. For example, Amphithol 20HD (manufactured by Kao Corporation), which is an amphoteric surfactant that is used in shampoos and the like and is less irritating to the skin, can be used.

The concentration of component (B) is 0.003 to 3.0% by mass, preferably 0.01 to 0.3% by mass. If the concentration of component (B) is less than 0.003% by mass, the synergistic effect when combined with component (A) is insufficient, and if it exceeds 3.0% by mass, the synergistic effect does not change, but the cost increases. It is not preferable because

[(C) Water]
Water (component (C)) used in the cleaning agent of the present invention includes tap water, hard water, soft water, ion-exchanged water, pure water, and purified water. From the viewpoint of the storage stability of the composition, it is preferable to use soft water, ion-exchanged water, pure water, purified water, or the like. Antiviral activity can be maintained. Hard water is defined as having a hardness of more than 100 mg/L, and soft water is defined as having a hardness of less than 100 mg/L.

In the cleaning agent of the present invention, water is blended in an amount (so-called balance) necessary for the sum of other components to be 100% by mass.

[(D) Additive]
The anti-enveloped virus detergent of the present invention may optionally contain surfactants, chelating agents, water-soluble solvents, etc. other than components (A) and (B).

(Surfactant)
The surfactant as component (D) is not particularly limited as long as it is other than components (A) and (B). Examples include cationic surfactants other than component (A), anionic surfactants agents, amphoteric surfactants other than component (B), and nonionic surfactants. Among them, nonionic surfactants having wetting, penetrating, washing, emulsifying and dispersing functions are preferred. Examples of nonionic surfactants include polyoxyalkylene alkyl ethers such as polyoxyethylene alkyl ethers and polyoxypropylene alkyl ethers, copolymers such as polyoxyethyleneoxypropylene block polymers, alkyl glycosides, nonylphenyl ethers, and the like. alkylphenyl ethers and carboxylic acid esters of Specific examples of surfactants include those disclosed in Patent Document 2, for example. In the present invention, polyoxyethylene alkyl ether is particularly preferred. As the polyoxyethylene alkyl ether, commercial products such as Noigen TDX80D (manufactured by Daiichi Kogyo Seiyaku Co., Ltd.) may be used.
The concentration of the surfactant in the detergent can be 0.002 to less than 0.2% by mass.

(chelating agent)
As the chelating agent, those commonly used in antibacterial detergents can be used, and examples thereof include at least one selected from hydroxycarboxylic acids and salts thereof, and aminocarboxylic acids and salts thereof. Examples of hydroxycarboxylic acids include citric acid, malic acid, gluconic acid, succinic acid, tartaric acid, and lactic acid. Examples of aminocarboxylic acids include methylglycinediacetic acid, ethylenediaminetetraacetic acid (EDTA), nitrilotriacetic acid, and diethylenetriaminepentaacetic acid. , hydroxyethylethylenediaminetetraacetic acid, and the like. These salts include alkali metal salts, alkaline earth metal salts, ammonium salts and alkanolamine salts. Aminocarboxylic acids or salts thereof are preferred in terms of availability, detergency, and storage stability. In the composition of the present invention, the chelating agent selected from the above may be used alone, or two or more thereof may be used in combination. For example, ethylenediaminetetraacetic acid (EDTA) can be suitably used in the cleaning agent of the present invention.

In the cleaning agent of the present invention, the chelating agent can be set in the range of 0.1 to 5% by mass, preferably 0.5 to 3% by mass. If the amount of the chelating agent is too small, the cleaning effect and the storage stability of the cleaning agent may be poor. , it may be economically disadvantageous.

The cleaning agent of the present invention contains a surfactant such as nonionic polymer polyether that stabilizes cations, and a chelating agent such as EDTA, so that the solution does not become turbid even at low temperatures. . In addition, by adding nonionic polymer polyether, etc., the antiviral activity can be maintained regardless of whether the water to be diluted is soft or hard water due to its chelating effect.

(water-soluble solvent)
As the water-soluble solvent, those commonly used in antibacterial detergents can be used, and examples thereof include at least one selected from glycol ether solvents and alcohols. Specific examples of the water-soluble solvent include those disclosed in Patent Document 2, for example.

In the cleaning agent of the present invention, the water-soluble solvent selected from the above may be used alone, or two or more of them may be used in combination.

The cleaning agent of the present invention can contain a water-soluble solvent in an amount set in the range of 0 to 20% by mass, preferably 5 to 15% by mass, more preferably 7 to 10% by mass.

(other ingredients)
In addition, the cleaning agent of the present invention may further contain other additives such as skin irritation mitigating agents, dyes, fragrances, preservatives, metal corrosion inhibitors, hop extracts, and disinfectants such as polylysine, if necessary. can do.

<Preparation of anti-envelope virus detergent>
When the cleaning agent of the present invention contains liquid components, it is generally mixed and stirred, and when it contains solid components, it is generally dissolved in water first, then added with other liquid components, and mixed and stirred. However, depending on the composition, the order of addition of each component, the order of dissolution, heating /
Manufacturing procedures such as cooling are not particularly limited.

The pH of the anti-enveloped virus detergent of the present invention (JIS Z 8802:2011 "pH measurement method") is 6 to 8 (neutral range) at 25°C. In the present invention, by setting the pH of the cleaning agent within the above range, the effect on the human body and the like can be reduced, and an effect of inactivating enveloped viruses can also be exhibited.
The pH is adjusted using an alkali agent such as an alkali metal hydroxide, carbonate, hydrogen carbonate, or carboxylate, preferably an alkali metal hydroxide, more preferably sodium hydroxide and/or potassium hydroxide, It can be adjusted within the above range.

The anti-envelope virus detergent (composition) of the present invention may be used after being diluted appropriately, for example, 2 to 1000 times. Dilution can be carried out using water (hardness 0 to 1000 (unit: mg/L, hereinafter the same)).

<Target virus>
The target virus of the anti-enveloped virus detergent of the present invention is not particularly limited, and can be a virus having an envelope. For example, novel coronavirus (SARS-CoV-2) and its variants, influenza viruses (types A, B and C), avian influenza virus, SFTS virus (severe fever with thrombocytopenia syndrome), Ebola virus, coronavirus (MERS , SARS, etc.), dengue fever, Zika fever, swine fever virus (CSFV), ASFvirus (African swine fever), yellow fever virus, Japanese encephalitis virus, St. Louis encephalitis, Murray Valley encephalitis, West Nile fever, Central European encephalitis, Russian spring and summer encephalitis, hepatitis B virus, hepatitis C virus, hepatitis D virus, rubella virus, Sindbis virus, chikungunya virus, eastern equine encephalitis virus, western equine encephalitis virus, Venezuelan equine encephalitis virus, human T lymphotropic virus, Human Immunodeficiency Virus (HIV), Marburg Virus, Rabies Virus, California Encephalitis Virus, Hunter'n Virus, Crimean-Congo Hemorrhagic Fever Virus, Rift Valley Fever Virus, Togoto Virus, Dori Virus, Parainfluenza Virus, Mump Virus, Measles Virus, Respiratory syncytial virus, Lassa virus, lymphocytic choriomeningitis virus, Hunni virus, Machupo virus, Guanarito virus, human herpes virus, human herpes virus 2-8, smallpox virus, bovine viral diarrhea virus 1 and 2, border disease virus 1, 2 and 3, giraffe pestivirus, and the like. Among them, the target viruses are influenza virus, novel coronavirus (SARS-CoV-2) and its variants, avian influenza virus, SFTS virus (severe fever with thrombocytopenia syndrome), Ebola virus, coronavirus (MERS, SARS), For dengue fever, Zika fever, swine fever virus (CSFV), and ASFvirus (African swine fever), the anti-envelope virus detergent of the present invention exhibits excellent virus inactivation ability.
The anti-enveloped virus detergent of the present invention has little effect on humans and livestock, and has a high inactivation ability against enveloped viruses as described above. Therefore, it is effective for decontamination of enveloped viruses, and has a very high utility value as a countermeasure against infectious diseases in humans and livestock.

<Disinfectant composition>
The disinfectant composition of the present invention contains the anti-enveloped virus detergent described above.
In addition to the anti-enveloped virus detergent, the antiseptic composition may optionally contain the additives described above.

<Virus inactivation method>
The present invention also provides a method for inactivating an enveloped virus, which comprises contacting an enveloped virus with the anti-enveloped virus detergent of the present invention or the disinfectant composition of the present invention to inactivate the enveloped virus. offer.
The anti-enveloped virus detergent or disinfectant composition (hereinafter collectively referred to as the "composition of the present invention") has a low concentration of the quaternary ammonium salt of component (A), so it is not harmful to the human body. low impact. On the other hand, since the coexisting component (B) sulfobetaine synergistically improves the antiviral properties of the ammonium cation, the composition of the present invention has the ability to inactivate enveloped viruses including the novel coronavirus. high.
Since enveloped viruses are inactivated using such a composition of the present invention, more efficient and sufficient virus inactivation can be achieved without causing unintentional spread of the virus.

An object to be washed using the composition of the present invention can be washed by the following method.
(1) The composition of the present invention can be impregnated into a nonwoven fabric to form an antiviral cleaning material (hereinafter sometimes referred to as the "antiviral cleaning material of the present invention"), which can be used to inactivate viruses. By performing the wiping operation on the object to be washed, the virus can be inactivated and the object to be washed can be washed. Items to be washed include medical sites, nursing care sites, food factories, coffee shops, restaurants, hotels, pubs, schools (school lunches), central kitchens, kitchen counters such as supermarket backyards, refrigerators, storage, tables, Examples include desks, doorknobs of entrances and exits, toilet bowls and toilet seats, faucets, floors, walls, and other hard surfaces. In addition, the antiviral cleaning material of the present invention can also be used as wet towels, wet tissues, and the like. In particular, according to the antiviral cleaning material of the present invention, even if the object to be cleaned is contaminated with organic dirt, the virus inactivation and the object to be cleaned can be inactivated by wiping without reducing or losing the virus inactivation effect. cleaning can be performed. The antiviral cleaning material of the present invention can be used, for example, for cleaning livestock barns, or can be spread on roads.

Raw materials for the nonwoven fabric that constitutes the antiviral cleaning material of the present invention include cellulosic materials such as cotton, protein materials such as wool or silk, and chemical polymerization materials such as rayon, polyester, and acrylic. Among them, cellulosic materials and chemically polymerized materials are preferable.

(2) In addition to the above, the composition of the present invention can be used by other suitable methods. For example, it may be sprayed onto the surface of the object to be cleaned by spraying or the like, allowed to stand for a predetermined time, rinsed with water as appropriate, and then dried. Specifically, a special dispenser containing the composition of the present invention is used to spray the surface of the object to be cleaned each time it is used, thereby inactivating the virus and cleaning the object to be cleaned. be able to. Examples of the object to be washed include those described above.

The composition of the present invention is provided by being filled in a plastic container, a container with a pump, a pouch, a tube, or the like. Moreover, it is also possible to individually pack a considerable amount to be used each time and provide it with portability.

EXAMPLES The present invention will be specifically described below using Examples and Comparative Examples, but the present invention is not limited to these.
In addition, below, pH is the value measured at 25 degreeC by JISZ8802:2011 "pH measuring method." In addition, the ability to inactivate enveloped viruses was evaluated using influenza virus (H3N2) and novel coronavirus as enveloped viruses. Moreover, "wt%" shall represent the mass %.

(Example 1-2, Comparative Example 1-5)
According to the composition in Table 1 below, each component was mixed at a ratio of sulfobetaine (10 wt% as Amphithol 20HD), water (89.5 wt%) and test sample (0.5 wt%), and the antiviral detergent composition of each composition prepared the product. All were colorless and transparent. A regulator (NaOHaq) was used for pH adjustment. In the table, the amount of each component is shown in % by mass. In the table, Amphithol 20HD (Kao products) is sulfobetaine, specifically lauryldimethyl-2-hydroxypropyl-3-sulfobetaine (see the formula below). Amphithol 20HD contains 30% by mass of the sulfobetaine.

Each antiviral detergent composition was diluted 100-fold with water (hardness 70) to make an anti-envelope virus detergent and used for the anti-influenza test.

The anti-influenza test (plaque method) was performed for influenza virus (H3N2) with an action time of 10 minutes. A regulator (NaOHaq) was used for pH adjustment. Regarding the effectiveness of the inactivation ability obtained by the plaque method, ◎: sufficient effect (4 Log10 or more), ○: effective (2 Log10 or more and less than 4 Log10), ×: no effect (less than 2 Log10).

The quaternary pyridinium salt in the table is cetylpyridinium chloride.

As shown in Table 1, the anti-envelope virus detergent of the present invention contains a specific quaternary ammonium salt and sulfobetaine at a specific concentration, so that the two exert a synergistic effect, Even at a low concentration of ammonium salt, it has a sufficient ability to inactivate enveloped viruses. Also, since the concentration of the quaternary ammonium salt is low, it has little effect on the human body.
On the other hand, in Comparative Examples 1-3 containing quaternary pyridinium salts and quaternary ammonium salts having a benzyl group, which do not correspond to the component (A) of the present invention, and in Comparative Example 4 containing no quaternary ammonium salts, enveloped viruses are inactivated. had no effect on conversion. In addition, the commercial product (Comparative Example 5) is effective in inactivating enveloped viruses, but has a high pH and has a large effect on the human body. Although the anti-enveloped virus detergent of Comparative Example 1-4 contained sulfobetaine, it was not effective in inactivating enveloped viruses. It can be assumed that there is no effect on

(Example 3-8)
According to the composition in Table 2 below, each component was mixed in the same manner as in Example 1 except that Noigen TDX80D (manufactured by Daiichi Kogyo Seiyaku Co., Ltd.) was used as the polyoxyethylene alkyl ether, and an antiviral detergent composition of each composition was prepared. prepared. All were colorless and transparent. A regulator (NaOHaq) was used for pH adjustment. In the table, the amount of each component is shown in % by mass.

Each antiviral detergent composition was diluted 100-fold with water (hardness 70) to make an anti-envelope virus detergent and used for the anti-influenza test. An anti-influenza test (plaque method) was performed for influenza virus (H3N2) with an action time of 5 minutes. The results were evaluated in the same manner as above.

As shown in Table 2, the anti-enveloped virus detergent of the present invention has sufficient ability to inactivate enveloped viruses at the sulfobetaine concentration of the present invention. In addition, whether the counter anion of the quaternary ammonium is chloride ion or bromide ion, it has sufficient ability to inactivate enveloped viruses.

(Example 9)
Didecyldimethylammonium chloride (0.4 g), Amphitol 20HD (10.0 g), Neugen TDX80D (2.0 g), EDTA (0.2 g), water (87.4 g, hardness 70) were mixed and used as an antiviral wash. A formulation composition was prepared. All were colorless and transparent. A regulator (NaOHaq) was used for pH adjustment (pH=7.2).
The composition of the antiviral detergent composition is as follows.
Part by mass Didecyldimethylammonium chloride 0.4
Sulfobetaine 3.0
Poly(oxyethylene) = alkyl ether 2.0
EDTA 0.2
Water Balance total 100

The antiviral detergent composition was diluted 100-fold with water (natural mineral water: Evian (registered trademark), (Kasha water source: hardness 304)) to form an anti-envelope virus detergent, which was used in the anti-influenza test. The effectiveness of the inactivating ability obtained by the plaque method was evaluated in the same manner as above while changing the exposure time (action time). Table 3 shows the results.

The anti-enveloped virus cleaning agent of the present invention exhibits sufficient ability to inactivate enveloped viruses with an exposure time of 1 minute even when a 100-fold concentrated solution is diluted with water having a hardness of 304. Activation ability can be maintained. This means that a compact 100-fold concentrate that is easy to transport can be diluted with hard water from hot springs or overseas (Las Vegas, Germany, Munich, China, Beijing, etc.) to maintain sufficient antiviral activity. means that
Dialkyl-type quaternary ammonium salts such as dialkyldimethylammonium salts are widely used compared to conventional cationic surfactant-type disinfectants in that they are less susceptible to hard water and have excellent disinfecting performance (Patent document 5). This also supports the results of the above tests (effects of the present invention).

(Example 10)
The anti-enveloped virus cleanser used in Example 9 was tested for skin irritation.
Tested according to the protocol of the Skin Irritation Test Set (OECD TG 439; In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method) to determine cell viability by anti-envelope virus detergents (surfactant formulations).

I-1. Preparation of test solution Positive control: 500 mg of SLS (sodium lauryl sulfate) was weighed and sterilized distilled water was added to make 10 mL.
Negative controls; sterile distilled water, phosphate buffer; 50 mM phosphate buffer (pH 7.2) were prepared and filled into sterilized poly wash bottles.
MTT medium; MTT reagent (6 mg) was dissolved in assay medium (12 mL). MTT [3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide] is a pale yellow substrate that is cleaved by the mitochondria of living cells to produce pale blue formazan (death not cleaved in cells). The amount of formazan produced correlates with the number of viable cells.
Test solution (test substance); Anti-envelope virus detergent prepared in Example 9

I-2. Test Procedure The assay medium was warmed in a 37°C water bath. 0.5 mL of assay medium was dispensed to the first row of four assay plates (4 rows x 6 columns). The culture cup was removed from within the LabCyte EPI-Model and transferred to a well of the assay plate dispensed with assay medium. The assay plate was placed in a sealed container containing a carbon dioxide culture pack, and cultured in a 25° C. incubator for 18 hours. 1.0 mL of the assay medium heated to 37° C. in a water bath was dispensed onto the third row of the assay plate removed from the incubator. The assay plate was placed in a sealed container containing a carbon dioxide culture pack, and cultured in an incubator at 25°C for 3 hours. 25 μL of test article was pipetted and dropped onto the cultured epidermis surface in row 1 (n=3). After 15 minutes of exposure to the test substance, the culture cup was taken out with forceps, and the inside of the cup was washed with a phosphate buffer. After repeating washing 15 times, excess phosphate buffer solution was wiped off the outside of the cup with a sterile cotton swab. The cup containing the washed cultured epidermis was transferred into the medium of row 3. After culturing, the assay plate was removed from the incubator, and 0.5 mL of MTT medium warmed in a water bath at 37° C. was dispensed into the wells of the fourth row. The assay plate was placed in a sealed container containing a carbon dioxide culture pack and cultured in an incubator at 25°C for 42 hours. The cultured epidermis was removed from row 3 and transferred to wells in row 4 containing MTT medium. The assay plate was placed in a sealed container containing a carbon dioxide gas culture pack, and cultured in a 25° C. incubator for 3 hours. After the reaction, the cultured epidermis in each well of row 4 was picked up with tweezers and placed in a 1.5 mL microtube. 300 μL of isopropanol was added to completely immerse the cultured epidermis. The dye was extracted by leaving it in a refrigerator for 48 hours, and the absorbance at 570 nm and 650 nm of the MTT reaction extract was measured. The viable cell rate was calculated by applying the following formula.

Measured value = [absorbance of specimen (570 nm) - absorbance of specimen (650 nm)] - [absorbance of blank (570 nm) - absorbance of blank (650 nm)]

Viability = (average test article measurements/average negative control measurements) x 100 (mean value is the average of n = 3 tests)

I-3. Judgment Criteria Viable cell rate: 50% or less --- Judged as irritating.
More than 50% of viable cells -- Judged as non-irritating.

Judgment: The viable cell rate was 104%, and no skin irritation was confirmed in the surfactant formulation prepared this time.

In Japan, solutions of didecyldimethylammonium chloride (DDAC) with a concentration of 0.4 wt% or more are designated as deleterious substances. However, the anti-envelope virus cleaning agent of the present invention exhibits anti-influenza activity in a 0.004 wt % aqueous solution at a concentration of 1/100 of 0.4 wt %, which is the lower limit of the deleterious substance designation of DDAC, and does not damage the skin. (Cell viability: 104%) was confirmed.

(Manufacturing example)
An anti-enveloped virus detergent (DEA-171) was prepared as follows.
(1) Production of DEA-171 100-fold concentrated solution (antiviral detergent composition) Biocide ST-70H (manufactured by Taisho Technos): dialkyldimethylammonium cation (1.4 g titer as didecyldimethylammonium chloride 0.00) 8 g), sulfobetaine (20 g, Amphithol 20HD: containing 30% lauryldimethyl-2-hydroxypropyl-3-sulfobetaine), Neugen TDX80D (manufactured by Daiichi Pharmaceutical Co., Ltd.): poly(oxyethylene) = alkyl ether (4. 0 g) was mixed with water (150 g, Lawson's natural water (hardness 59)) and homogenized (pH=7.6). To this, 20 g (0.4 g as EDTA) of a 2% EDTA (ethylenediaminetetraacetic acid 2Na) aqueous solution dissolved in preliminarily prepared "Lawson Natural Water" was slowly added. When uniform, the total amount was adjusted to 200 g with water to obtain an antiviral detergent composition (100-fold concentrate of DEA-171). The pH of this detergent composition was pH 7.1.
(2) Production of DEA-171 and DEA-172 (4-fold diluted solution of DEA-171) 20 g of the antiviral detergent composition (100-fold concentrated solution of DEA-171) produced in (1) 2 kg of DEA-171 was produced by diluting with 1.98 kg of tap water (hardness 61) from Katsushika Ward, Tokyo. The pH was 6-8.

The composition of DEA-171 is as follows.
Parts by mass Dialkyldimethylammonium salt 0.007
(0.004 as didecyldimethylammonium chloride)
Sulfobetaine 0.030
Poly(oxyethylene) = alkyl ether 0.020
EDTA 0.002
Water 99.941
Total 100

Furthermore, 300 g of water (tap water in Katsushika Ward) was added to 100 g of this DEA-171 to make DEA-172 (anti-envelope virus detergent). The pH was 6-8.

(Example 11) Novel coronavirus inactivation test To 100 μL of virus solution, 900 μL of anti-envelope virus detergent (DEA-171) was added, and after reacting for 1 minute and 30 minutes, the reaction solution was serially diluted 10 times. Immediately after that, the virus titer of the reaction solution was measured by the plaque method (performed in triplicate).
Regarding the effectiveness of the inactivation ability obtained by the plaque method, ◎: sufficient effect (3.8 Log10 or more), ○: effective (2 Log10 or more and less than 3.8 Log10), ×: no effect (less than 2 Log10) and

All strains inactivated the virus to below the detection limit with a sensitization time of 1 minute.
In addition, persistence of 30 minutes or more was also observed, unlike alcohol.

Subsequently, DEA-172 was also evaluated in the same way.

Compared to the concentration of 0.01 wt% (contact time of 5 minutes) at which dialkyldimethylammonium cations are currently said to be effective against the new corona, this is about one-tenth the concentration and one-fifth the time. It means that it came out.

(Example 12) Biological safety (reverse mutation: Ames) test of DEA-171 The test method conformed to OECD TG471.
Test and results:
A reverse mutation test was performed using 5 strains (TA100, TA98, TA1535, TA1537, WP2uvrA) described in OECD TG471. In this test, both S9Mix (-) and S9Mix (+) were tested using the product concentration. No mutant colony numbers were observed. That is, the mutagenicity of DEA-171 is negative.

(Example 13) Biological safety (skin sensitization) test of DEA-171 A skin sensitization test was conducted as follows.
Test mouse; CBA/J (Charles River Japan)
Group 1; negative control (NC); acetone:olive oil (4:1 v/v)
Second group; DEA-171 (undiluted solution)
Group 3; positive control (PC); 25% hexylcinnamaldehyde Each mouse was measured for (1) body weight and (2) determination of auricular erythema, and (3) ATP concentration in the auricular lymph node.

Test results:
In mice to which DEA-171 was applied, (1) no abnormal changes in body weight were observed. (2) Erythema was not confirmed. (3) No change in ATP concentration was confirmed.
Therefore, no skin sensitization was confirmed for DEA-171.

(Example 14) Confirmation of antibacterial action of DEA-171 and DEA-172 DEA-171 and DEA-172 showed antibacterial action against Escherichia coli and Staphylococcus aureus from 30 seconds to 10 minutes.

As described above, the anti-envelope virus cleansing agent (antiviral cleansing agent) of the present invention can be composed of 99% or more of water, is neutral, tasteless, odorless and transparent, and has skin sensitization and mutagenicity. Both sex and sex tests were negative, and no abnormalities were observed even after a single oral administration, indicating high safety.

In the present invention, by combining the components (A) and (B), the concentration of the quaternary ammonium salt, which is problematic when used alone in the human body, is reduced, thereby reducing the effects on the human body. A cleaning agent can be provided.
This is because the inactivating effect of the quaternary ammonium salt on the enveloped virus was confirmed by combining the component (B), which had not been reported for its inactivating effect against the enveloped virus, with the specific quaternary ammonium salt of the component (A). This is based on the fact that the present inventors discovered for the first time an unexpected synergistic effect of improving the
In particular, component (B) can adjust the balance of hydrophobicity and hydrophilicity of sulfobetaine and the distance between positive and negative charges by appropriately selecting substituents. A desired synergistic effect (inactivation effect against enveloped viruses) can be exhibited by appropriately adjusting these substituents according to the component (A) to be combined.

Furthermore, the anti-enveloped virus detergent of the present invention exhibits strong inhibitory activity not only against influenza viruses, but also against the enveloped virus novel coronavirus and its mutant strains. It can be assumed that the cations (positive charge) of the components (A) and (B) attack the negatively charged (anion) phospholipids that constitute the envelope, thereby inactivating the enveloped virus. In addition, even for viruses whose RNA genes are prone to mutation, such as the new coronavirus, the envelope phospholipid is derived from infected cells, so it is not affected by viral mutation, and has strong inhibitory activity against various mutant strains of the new coronavirus. indicates

Conventionally, the combination of a quaternary ammonium salt and a betaine-type amphoteric surfactant has been considered to reduce the bactericidal activity of the quaternary ammonium salt due to the ionic interaction of the surfactant. . The present invention surprisingly overturns such a conventional opinion, and exhibits the unexpected and remarkable effects as described above.

As described above, the anti-enveloped virus detergent of the present invention has a definite mechanism of action, is neutral and highly safe, and is strongly enveloped virus-specific (irrespective of the type and mutation of the virus gene). It is a cleaning agent that inactivates viruses and can be provided at a low cost. For this reason, it has high utility value as an effective infectious disease countermeasure against the serious risk of the rapid spread of infectious diseases caused by the new coronavirus, which the international community is facing.

The present invention is not limited to the above embodiments. The above-described embodiment is an example, and any device having substantially the same configuration as the technical idea described in the claims of the present invention and exhibiting the same effect is the present invention. included in the technical scope of

Claims

The following components (A) and (B) are contained in the following proportions with respect to the entire composition, water is contained as component (C), and the pH of the composition (JIS Z 8802: 2011 "pH measurement method" ) is 6-8 at 25°C.
(A) a quaternary ammonium salt represented by the following general formula (1): 0.0001 to 0.4% by mass;

(In the formula, R 1 to R 4 are linear, branched or cyclic C1 to C18 hydrocarbon groups, R 1 and R 2 may together form a cyclic group, X is fluorine a halogen atom selected from an atom, a chlorine atom, a bromine atom and an iodine atom, a hydroxy group, an alkoxy group, an acyloxy group, an alkylsulfonate group, a dialkylphosphonate group, an adipate group, a methosulfate group, a bicarbonate group or a carbonate group. )
(B) Sulfobetaine as an amphoteric surfactant: 0.003 to 3.0% by mass
The anti-envelope virus detergent according to claim 1, wherein R 1 to R 4 are linear or branched C1 to C18 alkyl groups.
3. The anti-envelope virus detergent according to claim 1 or 2, wherein the sulfobetaine is represented by the following general formula (2).

(In the formula, R 5 to R 7 are an optionally substituted benzyl group or an optionally branched C1 to C18 alkyl group, and R 5 and R 6 together may be cyclic. Y is a C1 to C5 alkylene group.However, when Y is a C3 alkylene group, a substituent may be placed at the 2-position.)
The anti-envelope virus detergent according to any one of claims 1 to 3, wherein the quaternary ammonium salt is a dialkyldimethylammonium salt.
The anti-envelope virus detergent according to any one of claims 1 to 4, wherein the sulfobetaine is lauryldimethyl-2-hydroxypropyl-3-sulfobetaine.
Target viruses are influenza virus, novel coronavirus (SARS-CoV-2) and its variants, avian influenza virus, SFTS virus (severe fever with thrombocytopenia syndrome), Ebola virus, coronavirus (MERS, SARS), dengue fever, Zika The anti-enveloped virus cleansing agent according to any one of claims 1 to 5, characterized in that it is fever, classical swine fever virus (CSFV), and ASFvirus (African swine fever).
The target virus is a novel coronavirus (SARS-CoV-2) and its mutants, and the component (A) is contained in a proportion of 0.0001 or more and less than 0.01% by mass based on the entire composition. The anti-enveloped virus detergent according to claim 6, characterized in that:
A disinfectant composition comprising the anti-enveloped virus detergent according to any one of claims 1 to 7.
Contacting the enveloped virus with the anti-enveloped virus detergent according to any one of claims 1 to 7 or the disinfectant composition according to claim 8 to inactivate the enveloped virus A method for inactivating enveloped viruses.