JP2024044307A - Liquid virus-inactivating composition - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a liquid virus-inactivating composition that exhibits minimal skin irritation and superior virus inactivation effects.

SOLUTION: The present invention provides a liquid virus-inactivating composition comprising a quaternary ammonium salt (I) represented by the formula (I), with a pH of 4 or more and 9 or less (excluding liquid virus-inactivating compositions for treating fiber products). In the formula (I), R¹ and R² independently represent a C8-18 linear or branched alkyl group or C8-18 linear or branched alkenyl group, and at least one of R¹ and R² comprises a C12-14 linear or branched alkyl group, R³ is a methyl group or an ethyl group, R⁴ is a methyl group, X is chlorine, bromine, methyl sulfate or ethyl sulfate.

SELECTED DRAWING: None

COPYRIGHT: (C)2024,JPO&INPIT

Description

The present invention relates to a liquid virus inactivation composition.

To prevent viral infections, it is important to inactivate viruses in the living environment. Quaternary ammonium salts are known as active ingredients in liquid compositions that inactivate viruses (liquid virus inactivation compositions).

For example, Patent Document 1 proposes a method for inactivating viruses that involves applying a textile product treatment composition containing a triazine derivative and didecyldimethylammonium chloride (a quaternary ammonium salt) to viruses on textiles. The invention of Patent Document 1 aims to provide an excellent virus inactivation effect.

Japanese Patent Application Publication No. 2019-151945

Didecyldimethylammonium chloride provides excellent virus inactivation effects. However, didecyldimethylammonium chloride has a problem in that it is highly irritating to the skin and is not suitable for use in contact with the skin.

Therefore, the object of the present invention is to provide a liquid virus inactivating composition that is less irritating to the skin and has an excellent virus inactivating effect.

After extensive research, the inventors discovered that by including a quaternary ammonium salt with a specific number of carbon atoms and setting the pH at a specific level, it is possible to achieve both excellent virus inactivation effects and reduced skin irritation (low skin irritation), and thus completed the present invention.

The present invention has the following aspects.
[1] A quaternary ammonium salt (I) represented by the following formula (I):
A liquid virus inactivating composition having a pH of 4 or more and 9 or less (excluding liquid virus inactivating compositions for treating textile products).

In formula (I), R ¹ and R ² are each independently a linear or branched alkyl group having 8 to 18 carbon atoms or a linear or branched alkenyl group having 8 to 18 carbon atoms, and at least one of R ¹ and R ² contains a linear or branched alkyl group having 12 to 14 carbon atoms, R ³ is a methyl group or an ethyl group, R ⁴ is a methyl group, and X is chlorine, bromine, methyl sulfate, or ethyl sulfate.
[2] The liquid virus inactivating composition according to [1], wherein a ratio of the linear or branched alkyl group having 12 to 14 carbon atoms to the total mass of ^R1 and ^R2 in formula (I) is 50 mass% or more.
[3] The liquid virus inactivating composition according to [1] or [2], wherein the content of the quaternary ammonium salt (I) is 0.01 to 10 mass % relative to the total mass of the liquid virus inactivating composition.
[4] The liquid virus inactivating composition according to any one of [1] to [3], which is for use in hard surface treatment.
[5] The liquid virus inactivating composition according to any one of [1] to [3], which is a hand soap, a body soap, a hair dye, a shampoo, a conditioner, a hairspray, a kitchen detergent, a hand disinfectant, a facial cleanser or a skin care cosmetic.

According to the liquid virus inactivation composition of the present invention, there is little irritation to the skin and an excellent virus inactivation effect is achieved.

[Liquid virus inactivation composition]
The liquid virus inactivation composition of the present invention contains a quaternary ammonium salt (I) represented by the following formula (I).

In formula (I), R ¹ and R ² are each independently a straight chain or branched alkyl group having 8 to 18 carbon atoms or a straight chain or branched alkenyl group having 8 to 18 carbon atoms, and R ¹ and At least one of R ² contains a straight chain or branched alkyl group having 12 to 14 carbon atoms, R ³ is a methyl group or an ethyl group, R ⁴ is a methyl group, and X is chlorine, bromine, methyl sulfate or sulfuric acid. It is ethyl.

In formula (I), R ¹ is a linear or branched alkyl group or a linear or branched alkenyl group, and preferably a linear or branched alkyl group. When R ¹ is a linear or branched alkyl group, the virus inactivation effect can be further enhanced.
^R2 is the same as ^R1 .

In formula (I), the carbon number of the alkyl group or alkenyl group (hydrocarbon group) of ^R1 is 8 to 18, preferably 10 to 16, and more preferably 12 to 14. When the carbon number of the hydrocarbon group of ^R1 is equal to or more than the above-mentioned lower limit, irritation to the skin can be further reduced. When the carbon number of the hydrocarbon group of ^R1 is equal to or less than the above-mentioned upper limit, the virus inactivation effect can be further enhanced.
The number of carbon atoms in the hydrocarbon group of ^R2 is the same as the number of carbon atoms in the hydrocarbon group of ^R1 .

In formula (I), the proportion of the linear or branched alkyl group having 12 to 14 carbon atoms relative to the total mass of R ¹ and R ² is preferably 50% by mass or more, more preferably 60% by mass or more, even more preferably 80% by mass or more, and may be 100% by mass. When the proportion of the linear or branched alkyl group having 12 to 14 carbon atoms is equal to or more than the above lower limit, both the virus inactivation effect and low irritation to the skin can be more effectively achieved.
Here, "the proportion of linear or branched alkyl groups having 12 to 14 carbon atoms (hereinafter also referred to as "C12-C14 proportion") is 50 mass% or more" means that in the distribution of the carbon numbers of the hydrocarbon groups in ^R1 and ^R2 , the proportion of C12-C14 is 50 mass% or more.

In formula (I), X is chlorine, bromine, methyl sulfate, or ethyl sulfate. Chlorine or bromine is preferred, and chlorine is more preferred, as this further enhances the virus inactivation effect.

Examples of the quaternary ammonium salt (I) include didodecyldimethylammonium salt, ditetradecyldimethylammonium salt, dialkyldimethylammonium chloride, dialkyl(C14-18)dimethylammonium chloride, and the like.
Commercial products of quaternary ammonium salt (I) include Lipocard (registered trademark) 2C-75 (diasialkyldimethylammonium chloride) and Lipocard (registered trademark), both manufactured by Lion Specialty Chemicals Co., Ltd. Examples include 2HP-75 (dialkyl (C14-18) dimethylammonium chloride).

The content of the quaternary ammonium salt (I) can be adjusted appropriately depending on its usage form and inactivation method, but for example, the content of the quaternary ammonium salt (I) is 0.01 to 10% by mass based on the total mass of the liquid virus inactivation composition. It is preferably 0.01 to 2.0% by mass, more preferably 0.03 to 0.5% by mass. When the content of the quaternary ammonium salt (I) is at least the above lower limit, the virus inactivation effect can be further enhanced. When the content of the quaternary ammonium salt (I) is below the above upper limit, irritation to the skin can be further reduced.

The liquid virus inactivation composition of this embodiment may be used as it is, or may be used after diluting the stock solution with water. When using the stock solution diluted with water, it is preferable to dilute it so that the content of the quaternary ammonium salt (I) is within the range of 0.01 to 10% by mass based on the total mass.

The liquid virus inactivation composition of this embodiment may contain optional components such as water, a surfactant, a solvent, a pH adjuster, and a fragrance within a range that does not inhibit the virus inactivation effect.
Water serves as a solvent for liquid virus inactivation compositions.
Examples of water include tap water, purified water, distilled water, ion exchange water, pure water, ultrapure water, etc., and are not particularly limited.
The content of water is preferably 10 to 99.99% by mass, for example, based on the total mass of the liquid virus inactivation composition.

Examples of surfactants include nonionic surfactants such as polyoxyalkylene alkyl ethers, alkyl polyglucosides, and fatty acid alkanolamides, amphoteric surfactants such as amine oxides and betaines, and cations other than quaternary ammonium salts (I).

Examples of the solvent include ethanol, isopropanol, glycerin, 1,3-butylene glycol, 1,2-pentanediol, polyethylene glycol, dipropylene glycol, propylene glycol, isoprene glycol, diglycerin, and the like.

Examples of pH adjusters include lactic acid, citric acid, glycolic acid, succinic acid, tartaric acid, dl-malic acid, phosphoric acid, sodium phosphate, potassium carbonate, sodium bicarbonate, ammonium bicarbonate, sodium citrate, etc.

Examples of fragrances include fragrance compositions described in JP-A No. 2002-128658 and JP-A No. 2015-21076.

Other optional ingredients include chelating agents such as ethylenediaminetetraacetic acid (EDTA), and salts such as sodium sulfate, potassium sulfate, sodium sulfite, and sodium phosphate.

The content of these optional components is preferably, for example, 0 to 10% by mass relative to the total mass of the liquid virus inactivation composition.

The pH of the liquid virus inactivating composition is from 4 to 9, preferably from 5 to 8, and more preferably from 6 to 8. When the pH of the liquid virus inactivating composition is within the above range, irritation to the skin can be further reduced.
The pH of the liquid virus inactivating composition is determined by measuring the temperature of the measurement subject at 25° C. using a pH meter (Model MP230, manufactured by Mettler Toledo).

The viscosity of the liquid virus inactivating composition is, for example, preferably 10 mPa·s or less, more preferably 6 mPa·s or less. When the viscosity of the liquid virus inactivating composition is equal to or less than the above upper limit, the composition is easy to apply to the object to be treated and easy to spread. The lower limit of the viscosity is substantially equal to or more than 1 mPa·s, and preferably equal to or more than 2 mPa·s.
The viscosity of the liquid virus inactivating composition is determined by measuring the temperature of the measurement subject at 25° C. using a Brookfield type (B) viscometer at 60 rpm and reading the value after 60 seconds.

<Method for producing liquid virus inactivation composition>
Examples of the method for producing the liquid virus inactivation composition of the present embodiment include a method of mixing the above-mentioned quaternary ammonium salt (I) and optional components as needed.
As a method of mixing each component, for example, quaternary ammonium salt (I) and other components are added to a portion of water, mixed, and then the remainder of the water is added to make the total amount 100% by mass. One method is to do this. Further, as a method of mixing each component, all of the remaining components may be added to all of the water and mixed so that the total amount is 100% by mass.

The liquid virus inactivation composition is used as a so-called cleaner and can take various product forms.
The liquid virus inactivation composition may be placed in a container as it is to form a containerized article. Examples of containers for containerized articles include discharge containers such as spray containers and squeeze containers.
Examples of spray containers include aerosol spray containers, trigger spray containers (direct pressure type or pressure accumulation type), dispenser spray containers, and the like. These containers may be manually operated or electrically operated.
Examples of aerosol spray containers include those described in JP-A-9-3441, JP-A-9-58765, and the like. Examples of propellants include LPG (liquefied propane gas), DME (dimethyl ether), carbon dioxide gas, and nitrogen gas. These propellants may be used alone or in combination of two or more.
Examples of trigger spray containers include those described in JP-A-9-268473, JP-A-10-76196, and the like. Examples of pressure accumulating type trigger spray containers include those described in JP-A No. 2013-154276 and the like.
Examples of dispenser spray containers include those described in JP-A-9-256272 and the like.

The liquid virus inactivating composition may be a container-containing product contained in a refillable container. Examples of the refillable container include plastic containers. Examples of the plastic container include bottle containers and standing pouches.
An example of a standing pouch is described in JP-A-2000-72181. Preferred examples of the film constituting the standing pouch include a two-layer film having an inner layer of linear low-density polyethylene having a thickness of 100 to 250 μm and an outer layer of stretched nylon having a thickness of 15 to 30 μm, and a three-layer film having an inner layer of linear low-density polyethylene having a thickness of 100 to 250 μm, an intermediate layer of stretched nylon having a thickness of 15 μm, and an outer layer of stretched nylon having a thickness of 15 μm.

The liquid virus inactivating composition may also be soaked into a woven or nonwoven fabric to form a sheet cleaner.

<How to use>
A method for using a liquid virus inactivating composition (i.e., a method for virus inactivation treatment) includes an operation of contacting an article to be treated with the liquid virus inactivating composition (contact operation). After the contact operation, a part or all of the liquid virus inactivating composition adhering to the article to be treated may be wiped off (wiping operation), or it may not be necessary to wipe off the liquid virus inactivating composition.

Examples of articles to be processed include articles having hard surfaces such as building equipment and living space fixtures. Examples of building equipment include floors, walls, doors, doorknobs, handrails, window glass, sashes, toilet bowls, toilet seats, bathrooms, kitchens, cooking tables, etc. of houses, etc. Examples of the living space fixtures include tables, chairs, partitions, electrical appliances, and the like.

Since the liquid virus inactivation composition of this embodiment causes less irritation to the skin, it can inactivate viruses even when it comes into direct contact with the skin. Examples of such uses include hand soaps, body soaps, hair dyes, shampoos, conditioners, hair sprays, kitchen detergents, hand sanitizers, facial cleansers, skin care cosmetics, and the like. Among these uses, hand soap, body soap, kitchen detergent, and hand sanitizer are preferred, and hand soap is more preferred. It can also be used as a livestock disinfectant and pet supplies.

The liquid virus inactivation composition of this embodiment can be used mainly for home use, but is not limited to home use, and can be used for industrial purposes, hospitals, nursing care facilities, restaurants, hotels, bathhouses, leisure facilities, and amusement facilities. It can also be applied to building maintenance, etc. Specifically, kitchens, refrigerators, and storage areas in medical settings, nursing care settings, food factories, coffee shops, restaurants, hotels, hot springs, public baths, bars, karaoke, schools (school lunches), central kitchens, supermarket backyards, etc. In addition, examples include tables, desks, doorknobs at entrances and exits, toilet bowls and seats, water faucets, floors, walls, windows, etc.

Methods for contacting the article to be treated with the liquid virus inactivating composition include, for example, coating the article in liquid form, spraying the composition in mist or foam form, and the like. Another method includes wiping the article to be treated with a woven or nonwoven fabric soaked in the liquid virus inactivating composition, such as a sheet cleaner.

In the contact operation, the liquid virus inactivation composition may be brought into contact with the article to be treated as it is (undiluted solution), or the liquid virus inactivation composition may be diluted with water to form a diluted solution, and this diluted solution may be used for treatment. It may also be brought into contact with the target article.
When diluting the liquid virus inactivation composition, the dilution rate expressed by [volume of diluent]/[volume of liquid virus inactivation composition before dilution] is preferably 1.1 to 30 times.
In the diluted liquid virus inactivating composition (diluent), the content of quaternary ammonium salt (I) is preferably 0.01 to 10% by mass based on the total mass of the liquid virus inactivating composition. .

Methods for wiping off a part or all of the liquid virus inactivating composition include, for example, wiping off with an implement such as a rag, mop, or brush. When using a sheet cleaner, the contact operation may also serve as the wiping operation.

In this way, by performing a contact operation, the item to be treated can be subjected to a virus inactivation treatment.

The liquid virus inactivating composition of the present invention contains a quaternary ammonium salt (I) as a virus inactivating agent, and therefore exerts an excellent virus inactivating effect.
In addition, since the liquid virus inactivating composition contains a quaternary ammonium salt (I), it can reduce irritation to the skin.
The liquid virus inactivating composition of the present invention has an excellent virus inactivating effect and can therefore be suitably used for articles having hard surfaces such as building facilities, room fixtures, etc. In other words, the liquid virus inactivating composition of the present invention is suitable for treating hard surfaces.
In addition, since the liquid virus inactivating composition of the present invention is less irritating to the skin, it can also be used in applications where it comes into direct contact with the skin, such as hand soap.

The present invention will be described in detail below with reference to examples, but the present invention is not limited to the following description.

[Ingredients used]
<Quaternary ammonium salts>
I-1: dioctyldimethylammonium chloride, trade name "Bardac LF-80", manufactured by Lonza, in which R ¹ and R ² in the formula (I) each have 8 carbon atoms, R ³ = R ⁴ = a methyl group, and X = chlorine.
I-2: Didecyldimethylammonium chloride, trade name "Lipocard (registered trademark) 210-80E", manufactured by Lion Specialty Chemicals Co., Ltd., in formula (I), R ¹ and R ² each have 10 carbon atoms, R ³ =R ⁴ =methyl group, X =chlorine, active ingredient 80 mass %.
I-3: Didodecyldimethylammonium chloride, manufactured by Tokyo Chemical Industry Co., Ltd., in formula (I), R ¹ and R ² each have 12 carbon atoms, R ³ =R ⁴ =methyl group, X =chlorine, active ingredient is 98% by mass or more, corresponds to quaternary ammonium salt (I).
I-4: dimethylditetradecylammonium bromide, manufactured by SIGMA ALDRICH, in formula (I), R ¹ and R ^{2 each} have 14 carbon atoms, R ³ =R ⁴ =methyl group, X =bromine, active ingredient 97% by mass or more, corresponds to quaternary ammonium salt (I).
I-5: dihexadecyldimethylammonium bromide, manufactured by SIGMA ALDRICH, in formula (I), R ¹ and R ² each have 16 carbon atoms, R ³ =R ⁴ =methyl group, X =bromine, active ingredient content is 97 mass% or more.
I-6: dimethyldioctadecylammonium bromide, manufactured by Tokyo Chemical Industry Co., Ltd., in formula (I), R ¹ and R ² each have 18 carbon atoms, R ³ =R ⁴ =methyl group, X =bromine, active ingredient 98 mass % or more.
I-7: dialkyldimethylammonium chloride, trade name "Lipocard (registered trademark) 2C-75", manufactured by Lion Specialty Chemicals Co., Ltd., the numbers of carbon atoms of R ¹ and R ² in formula (I) (C8 means that the number of carbon atoms is 8, and C10 means that the number of carbon atoms is 10. The same applies to C12, C14, C16, and C18 below); C8: 0.5 mass%, C10: 6 mass%, C12: 60 mass%, C14: 20 mass%, C16: 8 mass%, C18: 5.5 mass%, R ³ = R ⁴ = methyl group, X = chlorine, corresponds to quaternary ammonium salt (I).
Benzalkonium chloride: product name "Lipocard (registered trademark) CB-50", manufactured by Lion Specialty Chemicals Co., Ltd., active ingredient 50% by mass.

-Purified water: ultrapure water (Milli-Q (registered trademark) water).
pH adjuster 1: a mixture of 50 mM aqueous solution of trisodium phosphate 12-water (manufactured by FUJIFILM Wako Pure Chemical Industries, Ltd.) and 50 mM aqueous solution of phosphoric acid (manufactured by FUJIFILM Wako Pure Chemical Industries, Ltd.) (volume ratio of trisodium phosphate 12-water aqueous solution to phosphoric acid aqueous solution = 58:42), phosphate ion concentration 50 mM, pH = 8.
pH adjuster 2: a mixture of 50 mM aqueous solution of trisodium phosphate 12-water (manufactured by FUJIFILM Wako Pure Chemical Industries, Ltd.) and 50 mM aqueous solution of phosphoric acid (manufactured by FUJIFILM Wako Pure Chemical Industries, Ltd.) (volume ratio of trisodium phosphate 12-water aqueous solution to phosphoric acid aqueous solution = 26:74), phosphate ion concentration 50 mM, pH = 3.
pH adjuster 3: a mixture of a 50 mM aqueous solution of trisodium phosphate 12-water (manufactured by FUJIFILM Wako Pure Chemical Industries, Ltd.) and a 50 mM aqueous solution of phosphoric acid (manufactured by FUJIFILM Wako Pure Chemical Industries, Ltd.) (volume ratio of trisodium phosphate 12-water aqueous solution to phosphoric acid aqueous solution = 62:38), phosphate ion concentration 50 mM, pH = 10.

[Examples 1 to 12, Comparative Examples 1 to 7]
<Preparation of sample solution>
The amounts of each component were adjusted as shown in Tables 1 and 2, and a sample solution of a liquid virus inactivation composition was prepared according to the following procedure.
A quaternary ammonium salt was added to purified water and mixed. For Example 11, a quaternary ammonium salt was added to pH adjuster 1, for Comparative example 5, to pH adjuster 2, and for Comparative example 6, to pH adjuster 3, and the quaternary ammonium salts were added and mixed.
The pH was measured in a room at a room temperature of 25° C. using a pH meter (manufactured by Mettler Toledo, model number MP230) while stirring the sample solution. In Tables 1 and 2, the amounts of purified water or pH adjusters 1 to 3 added are the remaining amounts when the total amount of the sample solution is 100% by mass.
In addition, "-" in the table means that the component is not contained. The blending amounts in the table represent pure equivalent values, and the units are ppm on a mass basis.

[Measurement/evaluation method]
<Evaluation of virus inactivation effect>
(Preparation of cat kidney cells)
Minimum Essential Medium Eagle (E-MEM, manufactured by SIGMA, M4655-500ML), 3 mL of penicillin-streptomycin mixture (manufactured by SIGMA, P4333), and fetal bovine serum (FBS) inactivated by incubation at 56°C for 30 minutes. , Fetal Bovine Serum (manufactured by NICHIREI, 175012) was added to prepare a 5% FBS E-MEM culture solution.
Discard the culture supernatant of canine kidney cells (JCRB9029 MDCK (NBL-2)) cultured in a T-75 cell culture flask (manufactured by IWAKI, 75 cm ² , 270 mL, Cantonec, 3123-075), and add the culture supernatant to the flask. 10 mL of Dulbecco's phosphate buffered saline (PBS(-)) kept at 37°C was added to wash the cell surface and drained. Next, 2 mL of trypsin-EDTA (manufactured by GIBCO, TrypLE Express with Phenol Red, 12605-028) at 37°C was placed in the flask, and the mixture was allowed to stand at 37°C for 2 minutes to detach the cells from the flask. 8 mL of E-MEM culture solution not containing FBS was added thereto, the cells were suspended and extracted, and the cells were pelleted by centrifugation at 800 rpm for 5 minutes. The supernatant was removed, and approximately 8 mL of the 5% FBS E-MEM culture solution prepared as described above was added to prepare a cell suspension. 10 mL of 5% FBS E-MEM culture solution was placed in a T-75 cell culture flask, 2 mL of the cell suspension prepared as described above was added, and cultured at 37° C. in a CO ₂ incubator for 3 to 4 days.

(Preparation of MDCK cells for 96-well microplate evaluation)
The MDCK cells (canine kidney cells) cultured as described above were diluted 1/3 to 1/7 with 5% FBS E-MEM culture medium, and 0.2 mL of each dilution was added to a 96-well microplate (Nunc, 167008) and cultured in the same manner for 3 to 4 days.

(Preparation of virus concentrate)
The culture supernatant was removed from a T-75 culture flask in which the cultured cells had sufficiently proliferated (confluent) prepared according to the preparation of canine kidney cells, and the flask was washed twice with 10 mL of PBS(-). Influenza virus (Influenza A/PR/8/34 (H1N1) strain, ATCC strain VR-1469) was suspended in PBS (-) to a TCID50 of approximately 4 log/mL, and 1 mL of the suspension was added to the flask. added inside. After culturing at 37°C for 1 hour, 12 mL of Opti-MEM (manufactured by GIBCO, 31985-070) was added and cultured at 37°C. The estimated culture time was about 20 hours, and cell degeneration (CPE) was observed in about 90% of the cell culture area. The culture supernatant was collected and centrifuged at 4,000 rpm for 10 minutes, and the supernatant was filtered with a 0.2 μm membrane filter. Then, it was added to a centrifugal filter unit (Millipore, Amicon Ultra-15, 100 KDa, 50 mL container) and centrifuged at 4,000 rpm for 5 minutes to concentrate approximately 80 mL of the culture supernatant to 1 mL. A solution (virus concentrate) with a logarithm/mL of 1×8 was prepared.

(Method for evaluating virus inactivation effect)
50 μL of the virus concentrate prepared as above was added to 450 μL of the sample solution prepared as above, and the reaction was allowed to proceed at 25° C. for 1 minute. Then, 100 μL of the reaction solution was mixed with 900 μL of SCDLPB, which is a reaction stop solution, to stop the reaction. In order to prepare a 10-fold dilution series for the solution in which the reaction was stopped, 100 μL of the solution was diluted sequentially with 900 μL of SCDLPB. Next, the 5% FBS E-MEM culture medium was removed from the MDCK cells cultured on a 96-well microplate as described above, and 100 μL of each diluted solution of the 10-fold dilution series was added to each well, and the cells were left to stand at 37° C. for 1 hour in a CO ₂ incubator. Then, 200 μL of 5% FBS E-MEM culture medium containing 3 ppm trypsin was added to each well, and the cells were cultured at 37° C. for 5 days. The presence or absence of viral infection was observed under a stereomicroscope, and the viral infectivity (50% tissue culture infectious dose, TCID50) was determined. TCID50 was determined according to the Behrens-Karber method. The Behrens-Karber method is described in Hierholzer JC, Killington RA, Virus isolation and quantitation, In Mahy BWJ, Kangro HO (ed.), Virology methods manual, Harcourt Brace & Company, London, pp. 25-46 (1996).
log TCID50 = log (dilution in the first row) - (sum of (number of modified wells/total number of wells) in each dilution row - 0.5) x log (dilution rate)
The virus inactivation effect was evaluated based on the virus infectivity value and the following evaluation criteria. The results are shown in Tables 1 and 2.
"Evaluation criteria"
◎◎: Reduction in titer from blank virus infectivity was 3 or more.
⊚: The reduction in the virus infectivity titer from the blank was 2.5 or more and less than 3.
○: The reduction from the blank virus infectivity was 2 or more and less than 2.5.
×: The reduction in the virus infectivity titer from the blank was less than 2.
The term "blank" refers to a test performed in the same manner as described above using a solution prepared in the same manner as the sample solution, except that the quaternary ammonium salt represented by formula (I) was not added instead of the sample solution.

<Evaluation of skin irritation>
(Method of evaluating protein denaturation)
The skin irritation was evaluated by the following protein denaturation evaluation.
750 μL of an aqueous ovalbumin solution (concentration 0.5% by mass) and 750 μL of an aqueous quaternary ammonium salt solution (concentration 0.3% by mass) were placed in a vial and left at 40° C. for 20 hours. The solution was then filtered through a 0.45 μm filter and analyzed by liquid chromatography. Only the aqueous ovalbumin solution was treated under the same conditions and analyzed by liquid chromatography. Using these results, the protein denaturation rate was calculated according to the following formula.
Protein denaturation rate (%)=(1-(peak height after treatment with aqueous quaternary ammonium salt solution)/(peak height of untreated protein))×100
From the protein denaturation rate, the skin irritation was evaluated according to the following criteria. The results are shown in Tables 1 and 2.
"Evaluation criteria"
○: Protein denaturation rate is less than 15%.
Δ: Protein denaturation rate is 15% or more and less than 20%.
×: Protein denaturation rate is 20% or more.

As shown in Tables 1 and 2, in Examples 1 to 12 to which the present invention was applied, the virus inactivation effect was evaluated as "◎◎", "◎", or "○", and the skin irritation evaluation was " A rating of ``○'' or ``△'' indicates that both an excellent virus inactivation effect and less irritation to the skin were achieved.
On the other hand, in Comparative Example 1, in which the number of carbon atoms of R ¹ and R ² in formula (I) are both 8 and is outside the scope of the present invention, the virus inactivation effect was evaluated as "x". Comparative Example 2, in which R ¹ and R ² in formula (I) both have 10 carbon atoms and is outside the scope of the present invention, was evaluated for skin irritation as "x". In Comparative Examples 3 and 4, in which R ¹ and R ² in formula (I) both have 16 or 18 carbon atoms and are outside the scope of the present invention, the virus inactivation effect was evaluated as "x". Comparative Examples 5 and 6, in which the pH was outside the range of the present invention, were rated "x" for skin irritation. Comparative Example 7, in which benzalkonium chloride was used in place of the quaternary ammonium salt (I), was evaluated as "x" for virus inactivation effect.

From these results, it was found that the present invention causes less irritation to the skin and has an excellent virus inactivation effect.

Below is an example of a formulation using the liquid virus inactivating composition of the present invention. In the example below, each component is indicated by its name. The number written after each component indicates the content (mass%), with the total amount being 100 mass%. The amount of purified water "balance" indicates that the amount of purified water was adjusted so that the total amount was 100 mass%. "pH" indicates the value at 25°C.

[Prescription example 1: Hand soap 1]
Diasialkyldimethylammonium chloride: 1.0
Amidopropyl betaine laurate: 1.5
Polyoxyethylene lauryl ether: 2.0
Glycerin: 0.5
Propylene glycol: 0.5
Purified water: Total balance: 100
pH: 7

[Prescription example 2: hand mist 1]
Diasialkyldimethylammonium chloride: 0.05
Ethanol: 20 (volume%)
Glycerin: 0.3
Sodium citrate: 0.1
Polyoxyethylene hydrogenated castor oil: 0.2
Purified water: Total balance: 100
pH: 8

[Formulation example 3: Hard surface cleaning disinfectant 1]
Diasialkyldimethylammonium chloride: 0.1
Amidopropyl betaine laurate: 2
EDTA: 1
Sodium citrate: 1
Purified water: Total balance: 100
pH: 8

[Formulation example 4: Hard surface cleaning disinfectant 2]
Diasialkyldimethylammonium chloride: 1.0
Amidopropyl betaine laurate: 3.0
Propylene glycol: 3.0
Citric acid: 0.25
Purified water: Total balance: 100
pH: 7

[Formulation example 5: Hard surface cleaning disinfectant 3]
Diasialkyldimethylammonium chloride: 0.15
Polyoxyethylene tridecyl ether: 0.2
Amidopropyl betaine laurate: 0.8
Sodium citrate: 0.3
Ethanol: 1
Purified water: Total balance: 100
pH: 7

[Formulation Example 6: Hard Surface Cleaning and Disinfecting Agent 4]
Dialkyldimethylammonium chloride: 0.05
Myristyl dimethylamine oxide: 0.3
Trisodium methylglycine diacetate: 0.5
Sodium citrate: 0.3
Citric acid: 1
Purified water: Remainder Total: 100
pH: 7

[Formulation Example 7: Hard Surface Cleaning and Disinfecting Agent 5]
Dialkyldimethylammonium chloride: 0.05
Myristyl dimethylamine oxide: 0.1
Alkyl glucoside: 0.1
Purified water: Remainder Total: 100
pH: 7

[Formulation example 8: Hard surface cleaning disinfectant 6]
Diasialkyldimethylammonium chloride: 0.3
Myristyldimethylamine oxide: 6.0
Amidopropyl betaine laurate: 3.0
EDTA-3 sodium: 0.2
Ethanol: 4
Purified water: Total balance: 100
pH: 8

[Formulation Example 9: Hand Soap 2]
Dialkyldimethylammonium chloride: 1.5
Polyoxyethylene lauryl ether: 5.0
Lauryl dimethylamine oxide: 2.0
Coconut oil fatty acid diethanolamide: 1.5
Coconut oil alkyl dimethyl amino acetic acid betaine: 1.0
Disodium EDTA: 1.0
Purified water: Remainder Total: 100
pH: 7

[Formulation Example 10: Hand Soap 3]
Dialkyldimethylammonium chloride: 0.5
Lauryl glucoside: 2.5
Monoethanolamine: 0.05
Purified water: Remainder Total: 100
pH: 8

[Formulation Example 11: Hand Soap 4]
Dialkyldimethylammonium chloride: 1.0
Disodium EDTA: 0.75
Sodium laureth-4 carboxylate: 15
Purified water: Remainder Total: 100
pH: 7

[Prescription example 12: Hand mist 2]
Diasialkyldimethylammonium chloride: 0.2
Lactic acid: 0.2
Sodium lactate: 2.4
1,3-butylene glycol: 0.2
Purified water: Total balance: 100
pH: 5

[Prescription example 13: Hand mist 3]
Diasialkyldimethylammonium chloride: 0.1
Phosphoric acid: 1.0
Trisodium phosphate: 1.5
Ethanol: 30
Purified water: Total balance: 100
pH: 5

[Formulation Example 14: Hand Gel 1]
Dialkyldimethylammonium chloride: 0.05
Acrylic acid-alkyl methacrylate copolymer: 0.15
Ethanol: 40
Triethanolamine: 0.08
Sodium hyaluronate: 0.001
Glycerin: 0.2
Purified water: Remainder Total: 100
pH: 7

Claims (5)

Contains a quaternary ammonium salt (I) represented by the following formula (I),
A liquid virus inactivation composition having a pH of 4 or more and 9 or less (excluding liquid virus inactivation compositions for treating textile products).

In formula (I), R ¹ and R ² are each independently a straight chain or branched alkyl group having 8 to 18 carbon atoms or a straight chain or branched alkenyl group having 8 to 18 carbon atoms, and R ¹ and At least one of R ² contains a straight chain or branched alkyl group having 12 to 14 carbon atoms, R ³ is a methyl group or an ethyl group, R ⁴ is a methyl group, and X is chlorine, bromine, methyl sulfate or sulfuric acid. It is ethyl. 2. The liquid virus inactivating composition according to claim 1, wherein a ratio of the linear or branched alkyl group having 12 to 14 carbon atoms to the total mass of ^R1 and ^R2 in formula (I) is 50 mass% or more. The liquid virus inactivating composition according to claim 1 or 2, wherein the content of the quaternary ammonium salt (I) is 0.01 to 10% by mass based on the total mass of the liquid virus inactivating composition. . The liquid virus inactivating composition according to claim 1 or 2, which is for use in treating hard surfaces. The liquid virus inactivating composition according to claim 1 or 2, which is a hand soap, a body soap, a hair dye, a shampoo, a conditioner, a hair spray, a kitchen detergent, a hand sanitizer, a facial cleanser, or a skin care cosmetic.