Human norovirus inactivation agent

Abstract

The purpose of the present invention is to provide: a human norovirus inactivation agent having an excellent human norovirus inactivation effect; and a sanitary material. The present invention relates to a human norovirus inactivation agent characterized by having a pH of 1 to 6 and comprising (a) ethanol and (b) at least one acid selected from the group consisting of gluconic acid, fumaric acid, lactic acid, malic acid, succinic acid, citric acid, and phosphoric acid.

Description

Human norovirus inactivator

[0001] The present invention relates to an agent for inactivating human norovirus.

[0002] Some viruses can infect humans, and virus inactivators have been used to prevent infection.

[0003] In recent years, cases of infectious gastroenteritis or food poisoning caused by viruses such as human norovirus have been occurring frequently throughout the year, with peak occurrence occurring between November and March. Human norovirus, in particular, is a non-enveloped RNA virus classified in the Caliciviridae family and Norovirus genus, and is highly resistant to alcohol (ethanol, isopropanol, etc.), heat, acidity (gastric acid, etc.), and dryness. The incubation period is thought to be 1 to 2 days, and the main symptoms are nausea, vomiting, and diarrhea, but may also include abdominal pain, headache, fever, chills, muscle pain, sore throat, and fatigue.

[0004] Because human norovirus cannot be cultured, the inactivation of virus inactivating agents has been evaluated using closely related surrogate viruses, feline calicivirus and murine norovirus. For example, the inactivation of feline calicivirus and murine norovirus has been evaluated under protein-loaded conditions, and it has been speculated that formulations effective against both surrogate viruses will also be effective against human norovirus (see, for example, Patent Document 1).

[0005] Although acidic ethanol preparations have been reported to be highly effective in inactivating surrogate viruses, some acidic alcohol preparations on the market are not effective against human norovirus. Therefore, a composition that is effective against surrogate viruses may not necessarily be effective against human norovirus, and a composition that is ineffective against surrogate viruses may not necessarily be ineffective against human norovirus.

[0006] In recent years, the development of methods for propagating human norovirus, such as growing the virus in intestinal epithelial cells prepared from human iPS cell lines, has made it possible to directly evaluate the ability of acidic alcohol preparations to inactivate human norovirus (see, for example, Non-Patent Document 1).

[0007] Japanese Patent Application Laid-Open No. 2018-197205

[0008] Sato, S. , Matsumoto, N. , Hisaie, K. et al. Alcohol abrogates human norovirus infectivity in a pH-dependent manner. Sci Rep 10, 15878 (2020). <URL>https: / / doi. org / 10.1038 / s41598-020-72609-z

[0009] There is a demand for a human norovirus inactivating agent that has an excellent human norovirus inactivating effect, and for sanitary materials that contain the human norovirus inactivating agent.

[0010] The present invention has been made in view of the above-mentioned current situation, and an object of the present invention is to provide a human norovirus inactivating agent and a sanitary material that have excellent human norovirus inactivation effects.

[0011] That is, the present invention (1) relates to a human norovirus inactivating agent comprising (a) ethanol and (b) at least one acid selected from the group consisting of gluconic acid, fumaric acid, lactic acid, malic acid, succinic acid, citric acid, and phosphoric acid, and having a pH of 1 to 6.

[0012] "Human norovirus inactivating agents" refer to agents used to inactivate human norovirus. However, because they can be used to inactivate human norovirus, a type of non-enveloped virus that is highly drug-resistant, they can often also be used to inactivate other viruses.

[0013] The human norovirus inactivating agent of the present invention (1) contains (a) ethanol and (b) at least one acid selected from the group consisting of gluconic acid, fumaric acid, lactic acid, malic acid, succinic acid, citric acid, and phosphoric acid, and has a pH of 1 to 6, thereby exhibiting excellent human norovirus inactivation effects. In this specification, pH is a value measured by the method described in the Examples. At such a pH, the agent can exhibit human norovirus inactivation effects while more sufficiently preventing rough skin, such as rough hands, and further reducing the impact on the target object of use.

[0014] The human norovirus inactivating agent of the present invention (2) comprises (a) ethanol and (b) at least two acids selected from the group consisting of gluconic acid, fumaric acid, lactic acid, malic acid, succinic acid, citric acid, and phosphoric acid, and has a pH of 1 to 6.

[0015] The human norovirus inactivating agent of the present invention (2) contains (a) ethanol and (b) at least two acids selected from the group consisting of gluconic acid, fumaric acid, lactic acid, malic acid, succinic acid, citric acid, and phosphoric acid, and has a pH of 1 to 6, thereby exhibiting an excellent human norovirus inactivating effect.

[0016] The reason why the human norovirus inactivating agent of the present invention (1) or (2) exhibits such an excellent human norovirus inactivation effect is not entirely clear, but it is thought to be as follows: Viral infection and replication occur when the virus adsorbs to and invades the surface of a host cell, replicates the viral genome and synthesizes viral proteins within the cell, and then forms viral particles that are released outside the host cell. Although the details of the mechanism of virus inactivation are not clear, it is thought that ethanol and the acid of the present invention either denature the surface of the viral particles or destroy the viral particles themselves, thereby inhibiting the virus from adsorbing to and invading host cells.

[0017] The present invention (3) relates to the human norovirus inactivating agent of the present invention (1) or (2), wherein the mass proportion of the (a) ethanol is 25 mass% or more, thereby achieving a more excellent human norovirus inactivating effect.

[0018] The present invention (4) is the human norovirus inactivating agent according to any one of the present inventions (1) to (3), wherein the mass proportion of the (a) ethanol is 90 mass % or less.

[0019] The present invention (5) relates to the human norovirus inactivating agent according to any one of the present inventions (1) to (4), wherein the mass proportion of the acid (b) is 0.1 mass% or more, thereby achieving a more excellent human norovirus inactivating effect.

[0020] The present invention (6) relates to the human norovirus inactivating agent according to any one of the present inventions (1) to (5), wherein the mass proportion of the acid (b) is 2 mass% or less. The human norovirus inactivating agent of the present invention (6) exhibits a high virus inactivation effect against human norovirus while sufficiently preventing stickiness.

[0021] The present invention (7) also relates to a sanitary material containing the human norovirus inactivating agent of any of the present inventions (1) to (6). The human norovirus inactivating agent of the present invention sufficiently exhibits the human norovirus inactivating effect, and therefore, by using the sanitary material containing such a human norovirus inactivating agent, human norovirus infection can be prevented.

[0022] The human norovirus inactivating agent and sanitary material of the present invention can exhibit excellent human norovirus inactivation effects.

[0023] The present invention will be described in detail below. However, the present invention is not limited to the following embodiments, and can be applied by making appropriate modifications within the scope of the present invention.

[0024] A combination of two or more of the individual preferred embodiments of the present invention described below is also a preferred embodiment of the present invention.

[0025] <Human Norovirus Inactivating Agent> The human norovirus inactivating agent of the present invention comprises (a) ethanol and (b) at least one acid selected from the group consisting of gluconic acid, fumaric acid, lactic acid, malic acid, succinic acid, citric acid, and phosphoric acid (preferably, (b) at least two acids selected from the group consisting of gluconic acid, fumaric acid, lactic acid, malic acid, succinic acid, citric acid, and phosphoric acid), and has a pH of 1 to 6.

[0026] (Ethanol) The human norovirus inactivating agent of the present invention contains (a) ethanol. The mass proportion of (a) ethanol in 100% by mass of the human norovirus inactivating agent of the present invention is preferably 25% by mass or more, more preferably 30% by mass or more, even more preferably 35% by mass or more, and particularly preferably 40% by mass or more. The mass proportion of (a) ethanol is preferably 90% by mass or less.

[0027] (Acid) The human norovirus inactivating agent of the present invention contains (b) at least one acid selected from the group consisting of gluconic acid, fumaric acid, lactic acid, malic acid, succinic acid, citric acid, and phosphoric acid. From the viewpoint of improving the odor of the human norovirus inactivating agent, the acid is preferably gluconic acid, fumaric acid, lactic acid, malic acid, succinic acid, or phosphoric acid, more preferably gluconic acid, fumaric acid, lactic acid, or succinic acid, and even more preferably gluconic acid, fumaric acid, or lactic acid. From the viewpoint of improving the human norovirus inactivating effect, gluconic acid or fumaric acid is particularly preferred.

[0028] In terms of improving the human norovirus inactivation effect, the mass proportion of the (b) acid relative to 100% by mass of the human norovirus inactivator of the present invention is preferably 0.1% by mass or more, more preferably 0.3% by mass or more, even more preferably 0.5% by mass or more, and particularly preferably 1% by mass or more. In terms of further reducing the stickiness of the human norovirus inactivator, the mass proportion of the (b) acid is preferably 2% by mass or less, more preferably 1.5% by mass or less. The mass proportion of the (b) acid refers to the mass proportion of one or more of gluconic acid, fumaric acid, lactic acid, malic acid, succinic acid, citric acid, and phosphoric acid contained as the (b) acid in the human norovirus inactivator of the present invention. When the human norovirus inactivator of the present invention contains two or more of gluconic acid, fumaric acid, lactic acid, malic acid, succinic acid, citric acid, and phosphoric acid as the (b) acid, the mass proportion refers to the total mass proportion of the (b) acids.

[0029] Furthermore, the human norovirus inactivating agent of the present invention preferably essentially contains, for example, gluconic acid as the acid (b). When the human norovirus inactivating agent of the present invention essentially contains gluconic acid, the mass proportion of gluconic acid relative to 100% by mass of the human norovirus inactivating agent of the present invention is preferably 0.1% by mass or more, and more preferably 0.15% by mass or more. The upper limit of the mass proportion of gluconic acid is not particularly limited, but is preferably, for example, 2% by mass or less, more preferably 1% by mass or less. From the viewpoint of reducing stickiness of the human norovirus inactivating agent of the present invention, it is even more preferably 0.5% by mass or less. This allows the human norovirus inactivating agent of the present invention to be easy to handle while exhibiting excellent human norovirus inactivation effects.

[0030] For example, the human norovirus inactivating agent of the present invention preferably contains 0.1% by mass or more and 0.5% by mass or less of gluconic acid and, optionally, 0.3% by mass or more of gluconic acid and at least one acid selected from the group consisting of fumaric acid, lactic acid, malic acid, succinic acid, citric acid, and phosphoric acid. Here, fumaric acid, lactic acid, malic acid, succinic acid, citric acid, and phosphoric acid are not essential components but are optional components. This allows the human norovirus inactivating agent of the present invention to achieve both reduced stickiness and a human norovirus inactivation effect.

[0031] In particular, the human norovirus inactivating agent of the present invention preferably contains, as the acid (b), at least two acids selected from the group consisting of gluconic acid, fumaric acid, lactic acid, malic acid, succinic acid, citric acid, and phosphoric acid, thereby achieving a more excellent human norovirus inactivating effect.

[0032] The human norovirus inactivating agent of the present invention preferably includes (b) a combination of acids, for example, a combination of gluconic acid and lactic acid, a combination of fumaric acid and lactic acid, a combination of lactic acid and malic acid, a combination of lactic acid and succinic acid, a combination of lactic acid and citric acid, a combination of lactic acid and phosphoric acid, a combination of gluconic acid and fumaric acid, a combination of gluconic acid and malic acid, a combination of gluconic acid and succinic acid, a combination of gluconic acid and citric acid, a combination of gluconic acid and phosphoric acid, a combination of fumaric acid and malic acid, a combination of fumaric acid and succinic acid, a combination of malic acid and succinic acid, or a combination of succinic acid and citric acid.

[0033] Among these, it is more preferable that the human norovirus inactivating agent of the present invention contains a combination of gluconic acid and lactic acid, a combination of fumaric acid and lactic acid, a combination of lactic acid and succinic acid, a combination of lactic acid and phosphoric acid, a combination of gluconic acid and fumaric acid, a combination of gluconic acid and malic acid, a combination of gluconic acid and succinic acid, a combination of gluconic acid and citric acid, a combination of gluconic acid and phosphoric acid, a combination of fumaric acid and malic acid, a combination of fumaric acid and succinic acid, a combination of malic acid and succinic acid, or a combination of succinic acid and citric acid.

[0034] Furthermore, the human norovirus inactivating agent of the present invention preferably contains, as the acid (b), for example, lactic acid and / or gluconic acid as an essential component, and more preferably contains, for example, lactic acid as an essential component.

[0035] When the human norovirus inactivating agent of the present invention essentially contains lactic acid, the mass proportion of lactic acid is preferably 0.1 mass% or more, more preferably 0.2 mass% or more, and even more preferably 0.5 mass% or more, based on 100 mass% of the human norovirus inactivating agent of the present invention. The upper limit of the mass proportion of lactic acid is not particularly limited, but is preferably, for example, 2 mass% or less. This allows the human norovirus inactivating agent of the present invention to be easy to handle while exhibiting excellent human norovirus inactivation effects.

[0036] It is also more preferable that the human norovirus inactivating agent of the present invention essentially contains gluconic acid as the acid (b). When the human norovirus inactivating agent of the present invention essentially contains gluconic acid, the mass proportion of gluconic acid relative to 100% by mass of the human norovirus inactivating agent of the present invention is preferably 0.05% by mass or more. The upper limit of the mass proportion of gluconic acid is not particularly limited, but is preferably, for example, 2% by mass or less, more preferably 1% by mass or less, and from the viewpoint of reducing stickiness of the human norovirus inactivating agent of the present invention, even more preferably 0.5% by mass or less. This makes the human norovirus inactivating agent of the present invention easy to handle while exhibiting excellent human norovirus inactivation effects.

[0037] For example, the human norovirus inactivating agent of the present invention preferably contains, based on 100% by mass of the human norovirus inactivating agent, 0.2% by mass or more and 1.5% by mass or less of lactic acid and 0.3% by mass or more and 2.5% by mass or less of lactic acid and at least one acid selected from the group consisting of gluconic acid, fumaric acid, malic acid, succinic acid, citric acid, and phosphoric acid in a total amount of 0.3% by mass or more and 2.5% by mass or less of lactic acid and at least one acid selected from the group consisting of gluconic acid, fumaric acid, malic acid, succinic acid, citric acid, and phosphoric acid. It is particularly preferable that the human norovirus inactivating agent of the present invention contains 2% by mass or less of lactic acid and at least one acid selected from the group consisting of gluconic acid, fumaric acid, malic acid, succinic acid, citric acid, and phosphoric acid in a total amount of 2% by mass or less. This ensures that the human norovirus inactivating agent of the present invention has well-balanced and excellent performance.

[0038] Furthermore, for example, the human norovirus inactivating agent of the present invention preferably contains, as (b) acid, 0.05% by mass or more and 0.5% by mass or less of gluconic acid, and 0.3% by mass or more and 2% by mass or less of gluconic acid and at least one acid selected from the group consisting of lactic acid, fumaric acid, malic acid, succinic acid, citric acid, and phosphoric acid, in a total amount based on 100% by mass of the human norovirus inactivating agent. Of these, the human norovirus inactivating agent of the present invention more preferably contains 40% by mass or more and 90% by mass or less of (a) ethanol. Furthermore, the human norovirus inactivating agent of the present invention more preferably has a pH of 2 to 5.5.

[0039] For example, it is particularly preferred that the human norovirus inactivating agent of the present invention contains, based on 100% by mass of the human norovirus inactivating agent, (a) 40% by mass or more and 90% by mass or less of ethanol, (b) 0.05% by mass or more and 0.5% by mass or less of gluconic acid as an acid, and 0.3% by mass or more and 2% by mass or less in total of gluconic acid and at least one acid selected from the group consisting of lactic acid, fumaric acid, malic acid, succinic acid, citric acid, and phosphoric acid, and has a pH of 2 to 5.5. This ensures that the human norovirus inactivating agent of the present invention has well-balanced and excellent performance.

[0040] In the human norovirus inactivating agent of the present invention, the mass ratio of (a) ethanol to (b) acid ((a) / (b)) is preferably 1 to 500, more preferably 3 to 450, even more preferably 5 to 400, and particularly preferably 10 to 300.

[0041] (Inorganic Salt) The human norovirus inactivating agent of the present invention may further contain an inorganic salt. Examples of inorganic salts include magnesium sulfate, iron sulfate, copper sulfate, potassium sulfate, potassium bromide, sodium iodide, sodium sulfite, potassium sulfite, sodium nitrate, ammonium nitrate, sodium nitrite, potassium nitrite, ammonium nitrite, and sodium thiocyanate, and one or more of these may be used. Note that the inorganic salt typically exists in the form of a cation and an anion in the human norovirus inactivating agent.

[0042] When the human norovirus inactivating agent of the present invention contains an inorganic salt, the mass proportion of the inorganic salt is preferably 0.001 to 5 mass% based on 100 mass% of the human norovirus inactivating agent of the present invention.

[0043] (pH Adjuster) The human norovirus inactivating agent of the present invention may further contain a pH adjuster, such as an acidic agent such as sulfuric acid, hydrochloric acid, or sulfamic acid, or an alkaline agent such as sodium hydroxide, potassium hydroxide, sodium silicate, or potassium silicate. The amount of the acidic agent or alkaline agent can be appropriately adjusted depending on the desired pH.

[0044] (Water) The human norovirus inactivating agent of the present invention preferably further contains water. The water is not particularly limited, but examples thereof include tap water, distilled water, purified water, pure water, and ion-exchanged water. The mass concentration of water in the human norovirus inactivating agent of the present invention is preferably 0.1 to 90 mass%, more preferably 1 to 80 mass%, even more preferably 3 to 70 mass%, and particularly preferably 5 to 60 mass%.

[0045] (Surfactant) The human norovirus inactivating agent of the present invention may further contain a surfactant. Examples of the surfactant include anionic surfactants, cationic surfactants, nonionic surfactants, and amphoteric surfactants, and one or more of these can be used. In the human norovirus inactivating agent of the present invention, the concentration of the surfactant is preferably 10% by mass or less. The concentration of the surfactant is more preferably 1% by mass or less. Furthermore, it is even more preferable that the human norovirus inactivating agent of the present invention does not contain a surfactant. When multiple types of surfactants are used, the surfactant concentration refers to the total concentration of the multiple types of surfactants.

[0046] (Alcohols Other Than Ethanol) The human norovirus inactivating agent of the present invention may further contain an alcohol other than ethanol. Examples of alcohols other than ethanol include lower alcohols having 1, 3 to 5 carbon atoms, and one or more of these may be used. The concentration of the alcohol other than ethanol is preferably 40% by mass or less, based on 100% by mass of the human norovirus inactivating agent of the present invention. The concentration of the alcohol other than ethanol is more preferably 20% by mass or less, and even more preferably 10% by mass or less. It is particularly preferred that the human norovirus inactivating agent of the present invention does not contain any alcohol other than ethanol. When multiple types of alcohol other than ethanol are used, the concentration of the alcohol other than ethanol refers to the total concentration of the multiple types of alcohol other than ethanol.

[0047] (Organic Solvent Other Than Alcohol) The human norovirus inactivating agent of the present invention may further contain an organic solvent other than alcohol. However, the concentration of the organic solvent other than alcohol is preferably 40% by mass or less relative to 100% by mass of the human norovirus inactivating agent of the present invention. The concentration of the organic solvent other than alcohol is more preferably 20% by mass or less, and even more preferably 10% by mass or less. It is particularly preferable that the human norovirus inactivating agent of the present invention does not contain any organic solvent other than alcohol. When multiple organic solvents other than alcohol are used, the concentration of the organic solvent other than alcohol refers to the total concentration of the multiple organic solvents other than alcohol.

[0048] (Other Components) In addition to the above components, the human norovirus inactivating agent of the present invention may contain other components such as solubilizers, thickeners, enzymes, fragrances, coloring agents, dyes, etc. The mass proportion of these other components in 100% by mass of the human norovirus inactivating agent of the present invention is preferably 10% by mass or less, and more preferably 1% by mass or less.

[0049] (pH) The human norovirus inactivating agent of the present invention has a pH of 1 to 6. From the viewpoints of more adequately preventing rough skin such as rough hands and further reducing the impact on the target object of use, the pH is preferably 2 or higher, more preferably 2.5 or higher, and even more preferably greater than 3. From the viewpoint of further improving the human norovirus inactivation effect, the pH is preferably 5.5 or lower, more preferably 5 or lower, and even more preferably 4.5 or lower. As described above, the pH can be adjusted using a pH adjuster. The pH is measured at 25°C using the method described in the Examples.

[0050] <Uses> Next, uses of the human norovirus inactivating agent of the present invention will be described. As shown in the Examples below, the human norovirus inactivating agent of the present invention is effective in inactivating human norovirus and can be suitably used for inactivating human norovirus. Furthermore, the human norovirus inactivating agent of the present invention also exhibits a high virus inactivation effect against enveloped viruses such as influenza virus and coronavirus, which have lower drug resistance than human norovirus.

[0051] The human norovirus inactivating agent of the present invention may be added to a disinfectant. The human norovirus inactivating agent of the present invention or the disinfectant of the present invention may also be used in sanitary materials. The human norovirus inactivating agent of the present invention exhibits excellent virus inactivation effects against various viruses, including human norovirus, and therefore, by using a disinfectant containing such a human norovirus inactivating agent, viral infection can be sufficiently prevented.

[0052] The sanitary material of the present invention is not particularly limited, but examples thereof include masks, disposable gloves, disposable dish towels, tissue paper, wet tissues, and the like.

[0053] The human norovirus inactivating agent of the present invention may be added to a cleaning agent. The human norovirus inactivating agent of the present invention, and disinfectants and cleaning agents containing the human norovirus inactivating agent of the present invention, are preferably packed in pump bottles or spray bottles for use.

[0054] Examples are provided below to more specifically explain the present invention, but the present invention is not limited to these examples. In the examples, "%" means "% by mass" unless otherwise specified. In the tables of the examples, the mass percentage of each component is the mass percentage (% by mass) of the pure content, and the total of all components is 100% by mass.

[0055] (Examples 1-1 to 1-27, Examples 2-1 to 2-24, Examples 3-1 to 3-5) and (Comparative Examples 1-1 to 1-3, Comparative Example 2-1) Human norovirus inactivating agents according to Examples 1-1 to 1-27, Examples 2-1 to 2-24, Examples 3-1 to 3-5, and Comparative Examples 1-1 to 1-3 and 2-1 were prepared according to the formulations shown in Tables 1 to 5. The manufacturers of the compounds in Tables 1 to 5 are as follows:

[0056] <(a) Ethanol> Ethanol: Ethanol (99.5%) manufactured by Yoneyama Pharmaceutical Co., Ltd.

[0057] <(b) Acid according to the present invention> Gluconic acid: 50% gluconic acid solution manufactured by FUJIFILM Wako Pure Chemical Industries, Ltd. Fumaric acid: fumaric acid manufactured by FUJIFILM Wako Pure Chemical Industries, Ltd. Lactic acid: lactic acid manufactured by FUJIFILM Wako Pure Chemical Industries, Ltd. Malic acid: DL-malic acid manufactured by FUJIFILM Wako Pure Chemical Industries, Ltd. Succinic acid: succinic acid manufactured by FUJIFILM Wako Pure Chemical Industries, Ltd. Citric acid: citric acid manufactured by FUJIFILM Wako Pure Chemical Industries, Ltd. Phosphoric acid: phosphoric acid manufactured by FUJIFILM Wako Pure Chemical Industries, Ltd.

[0058] <(b)' Acids other than the acid according to the present invention> Acetic acid: acetic acid manufactured by Fujifilm Wako Pure Chemical Industries, Ltd. Tartaric acid: tartaric acid manufactured by Fujifilm Wako Pure Chemical Industries, Ltd. Ferulic acid: ferulic acid manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.

[0059] <Alcohols other than ethanol> Isopropanol: 2-propanol manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.

[0060] <Organic solvents other than alcohol> Propylene glycol: Fujifilm Wako Pure Chemical Industries, Ltd. Propylene glycol

[0061] <Surfactant> Polysorbate 60: Polysorbate 60 manufactured by NOF Corporation

[0062] <pH adjuster> Sodium hydroxide: 50 w / v% sodium hydroxide solution manufactured by Fujifilm Wako Pure Chemical Industries, Ltd. Hydrochloric acid: Hydrochloric acid manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.

[0063]

[0064]

[0065]

[0066]

[0067] Test Methods and Evaluation Criteria <pH Measurement> The pH of the undiluted solution of each composition was measured at 25°C using a pH meter F-53 (manufactured by Horiba, Ltd.) according to the method specified in JIS Z-8802:2011 "pH Measurement Method." The results are shown in Tables 1 to 5.

[0068] <Human Norovirus Inactivation Effect> [Preparation of Human Norovirus Solution] Nine parts of PBS were added to one part of feces collected from a human norovirus-positive patient and mixed. After centrifugation at 4°C and 10,000 g for 5 minutes, the supernatant was collected and filtered through a 0.22 μm membrane filter to be used as the human norovirus solution.

[0069] [Procedure for inactivating human norovirus using a human norovirus inactivator] 9 parts of a human norovirus inactivator were added to 1 part of a human norovirus solution diluted 10-fold with PBS, mixed, and allowed to act for 1 minute. After the act, the solution was diluted 10-fold with culture medium to stop the action of the human norovirus inactivator.

[0070] [Cultivation of human norovirus] A mixture of the inactivated human norovirus inactivator and human norovirus solution was inoculated onto human iPS cell-derived intestinal epithelial cells seeded in a 96-well flat-bottom plate, creating two plates, and cultured for 3 hours. The cells were then washed twice with medium, and 100 μL of culture medium was added. The cell monolayer and supernatant from one of the plates were collected, and the other plate was cultured for an additional 69 hours, for a total of 72 hours.

[0071] [Quantification of Human Norovirus Genome Amount] Monolayers of human iPS cell-derived intestinal epithelial cells 3 hours (3 hpi) and 72 hours (72 hpi) post-infection and RNase-treated supernatants were dissolved in a phenol extraction reagent, and quantitative RT-PCR was performed using a human norovirus-specific primer / probe set and the Luna® Universal Probe One-Step RT-qPCR Kit (Biolabs, E3006) according to the instruction manual to calculate the human norovirus genome amount.

[0072] Control: A human norovirus inactivator diluted 10-fold with culture medium was mixed with a human norovirus solution at a ratio of 99:1. This mixture was inoculated onto human iPS cell-derived intestinal epithelial cells seeded in a 96-well flat-bottom plate, creating two plates. One plate was cultured for 3 hours, and the other for 72 hours. The human iPS cell-derived intestinal epithelial cell monolayer and supernatant at 3 hours post-infection (hpi) and 72 hours post-infection (hpi) were dissolved in phenol extraction reagent, and quantitative RT-PCR was performed using a human norovirus-specific primer / probe set and the Luna® Universal Probe One-Step RT-qPCR Kit (Biolabs, E3006) according to the manufacturer's instructions to calculate the human norovirus genome amount.

[0073] [Evaluation of Human Norovirus Inactivation] The human norovirus genome amounts at 3 hpi and 72 hpi were compared to evaluate the degree of human norovirus inactivation. The evaluation criteria are as follows: ◎: The human norovirus genome at 3 hpi and 72 hpi was reduced to below the detection limit (inactivation was achieved by destroying virus particles). ○: The virus genome amounts at 3 hpi and 72 hpi were above the detection limit, but the genome amounts at 3 hpi and 72 hpi were equivalent, and the increase in genome amount was suppressed (inactivation was achieved by denaturing the surface of virus particles). △: The genome amount at 72 hpi increased compared to 3 hpi, but the increase was less than the control (some of the virus was inactivated). ×: The genome amount at 72 hpi increased compared to 3 hpi to the same or greater extent than the control (virus inactivation was not achieved). Note that a rating of △ or higher for human norovirus inactivation indicates a good human norovirus inactivation effect.

[0074] <Stickiness> Using a trigger sprayer T-95 Mist Trigger (manufactured by Canyon Co., Ltd.) with a spray volume of approximately 1 mL per spray, the human norovirus inactivator was sprayed once toward a polypropylene plate (manufactured by Nippon Test Panel Co., Ltd.) from a distance of approximately 25 cm, and then allowed to dry. The above process was repeated three times. After that, a sensory evaluation was conducted by touching the plastic surface with the hand. The evaluation criteria are as follows: ◎: No residual ingredients felt ○: Residual ingredients felt, but no stickiness △: Slightly sticky ×: Clearly sticky If the stickiness rating is △ or higher, the stickiness rating is good.

[0075] <Odor> After storing the human norovirus inactivating agent at 45°C for 30 days or more, a sensory evaluation was conducted to determine any odors other than ethanol. ◎: No unpleasant odor other than ethanol ○: An odor other than ethanol is detectable, but it is not unpleasant △: A slightly unpleasant odor other than ethanol is detected ×: A clearly unpleasant odor other than ethanol is detected An odor rating of △ or higher is considered to be good.

[0076] Tables 1 to 5 demonstrate that the human norovirus inactivating agents according to the examples exhibit excellent human norovirus inactivation effects. Furthermore, the human norovirus inactivating agents according to the examples are less sticky and have less odor, making them highly suitable for a variety of uses.

Claims

1. A human norovirus inactivating agent comprising: (a) ethanol; and (b) at least one acid selected from the group consisting of gluconic acid, fumaric acid, lactic acid, malic acid, succinic acid, citric acid, and phosphoric acid, and having a pH of 1 to 6.

2. A human norovirus inactivating agent comprising (a) ethanol and (b) at least two acids selected from the group consisting of gluconic acid, fumaric acid, lactic acid, malic acid, succinic acid, citric acid, and phosphoric acid, and having a pH of 1 to 6.

3. A human norovirus inactivating agent according to claim 1 or 2, wherein the mass proportion of (a) ethanol is 25 mass% or more.

4. A human norovirus inactivating agent according to claim 1 or 2, wherein the mass proportion of (a) ethanol is 90 mass% or less.

5. A human norovirus inactivating agent according to claim 1 or 2, wherein the mass proportion of the acid (b) is 0.1 mass% or more.

6. A human norovirus inactivating agent according to claim 1 or 2, wherein the mass proportion of the acid (b) is 2 mass% or less.

7. A sanitary material comprising the human norovirus inactivating agent according to claim 1 or 2.

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