JP2020033279A - Anti-norovirus agent, disinfectant and cleaning agent - Google Patents

Abstract

To provide a novel anti-norovirus agent that has a high norovirus inactivating effect, is plant-derived, and can safely inactivate norovirus for the human body.SOLUTION: Provided is an anti-norovirus agent containing, as an active ingredient, at least one selected from the group consisting of Mallotus japonicus extract, Cinnamomum cassia extract, St. John's Wort extract and mangosteen extract.SELECTED DRAWING: None

Description

  The present invention relates to anti-norovirus agents, disinfectants and cleaning agents.

  In recent years, infectious gastroenteritis and food poisoning caused by norovirus have occurred frequently throughout the year, and the peak of occurrence has been particularly high from November to March. Norovirus is a non-enveloped RNA virus classified into Caliciviridae and Norovirus, and has strong resistance to alcohol (ethanol, isopropanol, etc.), reverse soap, heat, acidity (gastric acid, etc.), drying, etc. Having. It is thought that the incubation period of norovirus is 1-2 days, and the main symptoms of nausea, vomiting and diarrhea appear, but it may also be accompanied by abdominal pain, headache, fever, chills, muscle pain, sore throat, malaise, etc. is there.

  Oral infection is known as one of the infection routes of norovirus, and infection is established by ingesting food, water and the like contaminated with norovirus. Therefore, in places where food is prepared and processed, such as restaurants, lunch facilities, and factories, it is required that food, water, equipment, and the like be not contaminated with norovirus.

  Norovirus has such high infectivity that it can be developed even when a small amount of about 10 to 100 is ingested. Therefore, anti-norovirus agents that act directly on norovirus and reduce or eliminate the infectivity of norovirus are desired.

  According to the Ministry of Health, Labor and Welfare, in order to inactivate norovirus, it is recommended that cooking utensils and the like be heated at 85 ° C. for 1 minute and disinfected with 200 ppm sodium hypochlorite (see Non-Patent Document 1). . However, inactivation of norovirus by heating has a problem of heat resistance of the object, and use of sodium hypochlorite is sometimes limited because of strong metal corrosiveness. Furthermore, in places with a lot of organic dirt such as a cooking place, it is assumed that sodium hypochlorite is decomposed and a sufficient effect cannot be obtained.

  In addition, sodium hypochlorite has a risk of invading the skin and mucous membranes, so it is difficult to apply it to the human body.Furthermore, care must be taken when handling and using it, as it reacts with acids to generate toxic gases. is there. Under such circumstances, there is a strong demand for an anti-norovirus agent which is easy to handle and can exert a sufficient inactivating effect even when sodium hypochlorite cannot be used.

  As a method for safely inactivating a norovirus or the like in a human body, a method using a virus-inactivated substance derived from food has been studied.

  For example, Patent Literature 1 discloses that a composition obtained by mixing a tannin-containing plant extract of the genus Persimmon with ethanol is used, and that this composition can be used to inactivate norovirus and the like.

WO 2008/153077 pamphlet

Ministry of Health, Labor and Welfare website “Q & A for Norovirus”; https://www.mhlw.go.jp/stf/seisakunitsuite/bunya/kenkou_iryou/shokuhin/syokuchu/kanren/yobou/040204-1.html#04

  As described above, Patent Document 1 discloses that a norovirus or the like can be inactivated by a composition containing an extract of a plant of the genus Persimmon containing tannin and ethanol. However, the inactivating effect of this composition on norovirus and the like cannot be said to be sufficient, and there is a need for a food-derived anti-norovirus agent that has a high inactivating effect on norovirus and can safely inactivate norovirus on the human body. ing.

  Under such circumstances, the main object of the present invention is to provide a novel anti-norovirus agent, which has a high norovirus inactivating effect, is plant-derived, and can safely inactivate the norovirus to the human body. And Another object of the present invention is to provide a disinfectant and a detergent using the anti-norovirus agent.

  The present inventors have conducted intensive studies in order to solve the above problems. As a result, it has been found that an extract derived from a specific food suitably suppresses infection by norovirus. The present invention has been completed by further study based on these findings.

That is, the present invention provides the following aspects of the invention.
Item 1. An anti-norovirus agent comprising, as an active ingredient, at least one selected from the group consisting of red wrinkle extract, cinnamon extract, St. John's wort extract, and mangosteen extract.
Item 2. Item 2. The anti-norovirus agent according to Item 1, wherein the content of the active ingredient is 0.01 to 10% (W / V).
Item 3. Item 3. The anti-norovirus agent according to item 1 or 2, further comprising at least one of water and a polar organic solvent.
Item 4. Item 4. The anti-norovirus agent according to any one of Items 1 to 3, wherein the pH is in the range of 2 to 10.
Item 5. Item 6. A disinfectant comprising the anti-norovirus agent according to any one of items 1 to 4.
Item 6. A cleaning agent comprising the anti-norovirus agent according to any one of items 1 to 4.

  According to the present invention, it is possible to provide a novel anti-norovirus agent which has a high inactivating effect of norovirus, is plant-derived, and can safely inactivate the norovirus to the human body. Further, according to the present invention, a disinfectant and a cleaning agent using the anti-norovirus agent can be provided.

  Hereinafter, the anti-norovirus agent of the present invention, a disinfectant and a cleaning agent using the same will be described in detail. In this specification, a numerical value connected by “to” means a numerical value range including numerical values before and after “to” as a lower limit value and an upper limit value. When a plurality of lower limits and a plurality of upper limits are separately described, it is assumed that any lower limit and upper limit can be selected and connected by “to”.

  The anti-norovirus agent of the present invention is characterized in that at least one selected from the group consisting of a red oak wrinkle extract, caffeine extract, St. John's wort extract, and a mangosteen extract is used as an active ingredient. In the anti-norovirus agent of the present invention, these active ingredients are derived from plants, have a high inactivating effect on norovirus, and can safely inactivate norovirus on the human body.

  The anti-norovirus agent of the present invention exerts an effect of reducing or eliminating the infectivity of norovirus by, for example, the active ingredient acting directly on the norovirus and affecting the structure of the capsid protein. That is, the anti-norovirus agent of the present invention can also be referred to as a norovirus infection inhibitor.

  The anti-norovirus agent of the present invention exhibits an effect of reducing or eliminating infectivity against viruses belonging to the genus Norovirus, and other Caliciviridae viruses, Picornaviridae viruses, and Parvoviridae (Parvoviridae). ) It shows a favorable effect of reducing or eliminating infectivity to non-enveloped viruses other than norovirus, such as viruses, Papillomaviridae virus, Polyomaviridae virus, and Adenoviridae virus. obtain.

  It is known that the effect of an anti-norovirus agent on norovirus can be confirmed by a virus-like particle (VLP) of a recombinant norovirus. For example, if the norovirus capsid protein encoded by ORF2 in cells from a baculovirus vector or the like in Sf9 cells is recombinantly expressed, as a result, the capsid proteins may spontaneously self-assemble into VLPs. In addition, when the norovirus protein encoded by ORF1 and ORF2 in a cell is recombinantly expressed from, for example, a baculovirus vector in an Sf9 cell, as a result, the capsid protein naturally self-organizes into a VLP. VLPs are structurally similar to Norovirus and similar in antigenicity, but lack the viral RNA genome and are therefore not infectious. Thus, the action of the anti-norovirus agent to reduce or eliminate the ability to infect the norovirus can be confirmed by the action of the anti-norovirus agent on the virus-like particles (VLP) of the recombinant norovirus.

  Norovirus has been found to recognize human tissue blood group antigen (HBGA) as a receptor. Among the tissue blood group antigens, the blood groups most frequently encountered are ABO (ABH) and Lewis, and Norovirus specifically binds to these antigens. The biosynthetic pathways utilized for antigen formation in the ABH, Lewis, P and I systems of blood groups are interrelated. Tissue blood group antigens have been associated with infection by several bacterial and viral pathogens. This suggests that the tissue blood group antigen is a recognition target for the pathogen and can promote entry into cells that express the antigen and form a receptor-ligand bond with the antigen. Although the exact nature of such interactions is currently unknown, the close association of pathogens with antigen binding may play a role in tethering pathogens to cells as an early step in the infection process. Human tissue blood group antigens are glycoconjugates bound to glycoproteins or glycolipids that are present on erythrocytes and mucosal epithelial cells or as free antigens in biological fluids such as blood, saliva, intestinal contents and milk. It is. These antigens are genetically controlled and synthesized by the sequential addition of monosaccharides to antigen precursors by several glycosyltransferases known as ABO, Lewis, and secreted gene families.

  As described above, the norovirus binds to the tissue blood group antigen on the cell surface as a receptor. By focusing on this binding, the effect of the anti-norovirus agent can be measured. (See Zhang XF et al. Bioorganic & Medicinal Chemistry. 2012.20: 1616-1623)

  Therefore, the effect of the anti-norovirus agent of the present invention for reducing or eliminating the infectivity of norovirus can be specifically referred to as the effect of inhibiting the binding of norovirus to HBGA.

  The specific evaluation of the inhibitory effect of the anti-norovirus agent of the present invention on the binding between norovirus and HBGA is performed as follows.

<Norovirus-HBGA binding inhibition assay as an anti-norovirus effect measurement>
A 96-well microtiter plate coated with HBGA derived from human saliva is washed, and a norovirus VLP solution treated with a sample containing a test component (anti-norovirus agent) is added to bind to HBGA. The plate is washed, chicken IgY specific for Norovirus VLP is added, washed, and then incubated with horseradish peroxidase-conjugated sheep anti-IgY antibody. Color with orthophenylenediamine hydrochloride basic and stop with 1N sulfuric acid. After coloring, it is measured at 492 nm. Norovirus VLPs that have lost the ability to bind to HBGA are not detected by this method. Therefore, the binding inhibitory effect of the test component (anti-norovirus agent) can be confirmed by comparison with the negative control.

  As described above, the anti-norovirus agent of the present invention is characterized in that it contains, as an active ingredient, at least one selected from the group consisting of a red oak extract, caffeine extract, St. John's wort extract, and a mangosteen extract.

  The red wrinkle extract is an extract of red wrinkles, for example, an extract of bark, leaves, roots, or a mixture thereof of red wrinkles, and is preferably an extract of bark. Examples of the extraction solvent include water; alcohols such as methanol, ethanol, propanol, and butanol; polyhydric alcohols such as ethylene glycol, propylene glycol, butylene glycol, and glycerin; ketones such as acetone and methyl ethyl ketone; methyl acetate and ethyl acetate. Esters such as tetrahydrofuran and diethyl ether; halogenated hydrocarbons such as dichloromethane, dichloroethane and chloroform; aliphatic hydrocarbons such as hexane and pentane; aromatic hydrocarbons such as toluene; polyethylene glycol and the like. And organic solvents such as pyridines. These extraction solvents may be used alone or in a combination of two or more. Among them, water, alcohol (for example, ethanol), hydrated alcohol (for example, hydrated ethanol) and the like are effective. That is, the red wrinkle extract is preferably a water extract, an alcohol extract, or a hydrous alcohol extract of red wrinkles. The red wrinkle extract may be used alone or in combination of two or more. In addition, examples of a commercial product of the red wrinkle extract include red wrinkle extract powder sold by Nippon Powder Chemical Co., Ltd.

  The cinnamon extract is a bark extract of the camphor tree Tonkinkei and other congeners (Katsui). As the camphoraceae tonkin keikei and other congener plants, for example, tonkin nikkei, javanici, ceylon nikkei and the like can be mentioned. Examples of the extraction solvent include the same solvents as those exemplified as the extraction solvent for the extract of Acacia catechu. Among them, water, alcohol (for example, ethanol), and hydrous alcohol (for example, hydrous ethanol) are effective. That is, the cinnamon extract is preferably an aqueous extract, an alcoholic extract, or a hydroalcoholic extract of the camphor tree Tonkinkei or other congener plants (Katsui). As the calyx extract, only one kind may be used, or two or more kinds may be used in combination. Examples of commercially available caffeine extract include caffeine extract sold by Nippon Powder Chemical Co., Ltd.

  St. John's wort extract is an extract such as leaves, stems, flowers, or mixtures thereof of St. John's wort (Hypericum perforatum). Examples of the extraction solvent include the same solvents as those exemplified as the extraction solvent for the extract of Acacia catechu. Among them, water, alcohol (for example, ethanol), and hydrous alcohol (for example, hydrous ethanol) are effective. That is, the St. John's wort extract is preferably an aqueous extract, an alcoholic extract, or a hydroalcoholic extract of St. John's wort. St. John's wort extract may be used alone or as a mixture of two or more. Examples of commercially available products of St. John's wort extract include St. John's wort extract powder sold by Tokiwa Plant Chemistry Laboratory Co., Ltd.

  Mangosteen extract is an extract such as mangosteen peel. Examples of the extraction solvent include the same solvents as those exemplified as the extraction solvent for the extract of Acacia catechu. Among them, water, alcohol (for example, ethanol), and hydrous alcohol (for example, hydrous ethanol) are effective. That is, the mangosteen extract is preferably a water extract, an alcohol extract, or a hydroalcoholic extract of mangosteen. One type of mangosteen extract may be used, or two or more types may be used in combination. Examples of commercially available mangosteen extract include mangosteen aqua sold by Nippon Shinyaku Co., Ltd.

  In the anti-norovirus agent of the present invention, the content of at least one selected from the group consisting of a red oak wrinkle extract, caffeine extract, St. John's wort extract, and mangosteen extract as the content of the active ingredient (the total content of these extracts) is determined to be norovirus. There is no particular limitation as long as it can be inactivated, but the lower limit is preferably 0.01% (W / V) or more, more preferably 0.05% (W / V) or more, and still more preferably 0.5%. (W / V) or more, and the upper limit is preferably 10% (W / V) or less, more preferably 5% (W / V) or less, and still more preferably 2% (W / V) or less. Can be

  The anti-norovirus agent of the present invention preferably further contains at least one of water and a polar organic solvent in addition to the above-mentioned active ingredient.

  The polar organic solvent is not particularly limited as long as it does not inhibit the effects of the present invention, but lower alcohols such as ethanol and isopropanol are preferable, and ethanol is more preferable. The anti-norovirus agent of the present invention preferably contains an aqueous ethanol solution.

  For example, when the anti-norovirus agent of the present invention is used as a disinfectant or detergent, the concentration of ethanol in the aqueous ethanol solution is about 43% by mass or more (about 50% by volume or more) for the lower limit and about 52% for the upper limit. The best range is about 43% by mass to about 52% by mass (about 50% to about 60% by mass). In addition, ethanol is generally known to exhibit high bactericidal properties at a high concentration of 60% by mass to 73% by mass (about 68% by mass to about 80% by volume), but is generally 52% by mass (about 60% by mass). An ethanol solution having a concentration exceeding (% by volume) may be deteriorated depending on the material of the object to be disinfected / washed, and the skin may become rough when attached to a finger or the like. Further, if it is 60% by mass or more, it is treated as a dangerous substance under the Fire Service Law, and there are cases where the handling is restricted. On the other hand, when quick-drying is required, if the concentration is lower than 43% by mass, it may be difficult to use because the amount of water is large and it is difficult to dry. When quick drying is not required and there is a possibility that the object to be disinfected and cleaned may be deteriorated by an organic solvent, it is preferable to use water as the solvent. From such a viewpoint, when the anti-norovirus agent of the present invention contains ethanol and is used as a disinfectant or a cleaning agent, the lower limit of the ethanol concentration is about 43% by mass or more (about 50% by volume or more), The upper limit is about 52% by mass or less, and the optimum range is about 43% by mass to about 52% by mass (about 50% by mass to about 60% by mass).

  From the viewpoint of enhancing the inactivating effect on norovirus, the pH of the anti-norovirus agent of the present invention is preferably in the range of 2 to 10, more preferably in the range of 3.5 to 7.0.

  The pH of the anti-norovirus agent of the present invention can be adjusted with a known pH adjuster or buffer. Examples of the pH adjuster include inorganic acids such as hydrochloric acid, nitric acid, sulfuric acid, and phosphoric acid; organic acids such as lactic acid, citric acid, succinic acid, gluconic acid, and ascorbic acid and salts thereof; Hydroxides of alkali metals; carbonates such as potassium carbonate and sodium hydrogencarbonate; Examples of the buffer include a phosphate buffer, a citrate phosphate buffer, and a lactate buffer. In the present invention, it is preferable to adjust the pH using an organic acid and an organic acid salt such as lactic acid and sodium lactate, ascorbic acid and sodium ascorbate.

  The anti-norovirus agent of the present invention includes, in addition to the above-mentioned active ingredient, water, and a polar organic solvent, other general anti-viral components such as acyclovir, phenoxyethanol, chlorhexidine gluconate, and benza chloride as long as the characteristics of the present invention are not impaired. General antibacterial components such as ruconium, benzethonium chloride, cetylpyridinium chloride, alkyldiaminoethylglycine hydrochloride, and isopropylmethylphenol can also be contained.

  In addition, even if glycerin fatty acid ester is added in order to enhance the eradication ability against general viable bacteria, there is no problem because it does not affect the inactivating effect on norovirus. Examples of glycerin fatty acid esters include glycerin monocaprate, glycerin monolaurate, glycerin monomyristate, glycerin monopalmitate, glycerin monostearate, glycerin monoisostearate, glycerin monooleate, and glycerin monobehenate. Glycerin monofatty acid esters such as acid esters; glycerin distearate esters, glycerin diisostearate esters, glycerin dioleate esters and the like; glycerin difatty acid esters; Monoglyceride derivatives and the like. In the present invention, one or more of these can be selected and used. It is preferable to use a glycerin monofatty acid ester of a fatty acid having 8 to 12 carbon atoms, such as glycerin monocaprylate, glycerin monocaprate, glycerin monolaurate, etc. from the viewpoint of enhancing the disinfecting power against general living bacteria.

  Further, the anti-norovirus agent of the present invention has a surfactant other than the glycerin fatty acid ester for the purpose of imparting detergency and foaming property within a range that does not affect the inactivation of the norovirus or the stability of the composition. Agents can be added. Examples of the surfactant include cationic surfactants such as primary to tertiary fatty amine salts, quaternary ammonium salts, and 2-alkyl-1-alkyl-1-hydroxyethylimidazolinium salts; Alkyl betaine type such as N, N-dimethyl-N-alkyl-N-carboxymethylammonium betaine; aminocarboxylic acid type such as N, N-dialkylaminoalkylenecarboxylic acid; N, N, N-trialkyl-N-sulfo An alkylsulfobetaine type such as alkylene ammonium betaine, and an imidazoline type amphoteric surfactant such as 2-alkyl-1-hydroxyethyl-1-carboxymethylimidazolinium betaine can be used. Water-soluble polymers such as gum arabic, carrageenan, sodium carboxymethylcellulose, hydroxycellulose, sodium polyacrylate; sodium ethylenediaminetetraacetate, and tripolyphosphoric acid for the purpose of increasing foaming, improving formulation stability, coloring, flavoring, etc. And sequestering agents such as hexametaphosphate; inorganic salts such as sodium chloride, potassium chloride and sodium sulfate; pigments;

  The anti-norovirus agent of the present invention can be used as a disinfectant or detergent (sterile detergent) by itself or by adding various carriers, other surfactants, and additional components such as a bactericide. That is, the disinfectant and the cleaning agent of the present invention each contain the anti-norovirus agent of the present invention.

  The disinfectant or cleaning agent of the present invention can be provided in various forms such as a liquid, a gel, and a powder. . The liquid disinfectant or cleaning agent can be provided as a lotion, spray, etc., filled into a bottle with a measuring cap, a trigger type spray container, a squeeze type or dispenser type pump spray container, and sprayed or sprayed. Can be used.

  The disinfectant or cleaning agent of the present invention can be used for disinfection, sterilization cleaning, furniture such as tables, chairs, bedding, tableware, cooking utensils, and medical supplies in facilities such as hospital rooms, living rooms, cooking rooms, bathrooms, toilets, and toilets. It can be widely used for disinfection, sterilization cleaning, etc. of instruments, devices, devices, and the like, where there is a possibility that a virus is present, or for disinfection, sterilization cleaning, and the like of a substance that may be contaminated with the virus.

  The disinfectant or cleaning agent of the present invention may be used in such an amount that the surface of the object to be disinfected is evenly wetted. In addition, the disinfectant or the cleaning agent of the present invention can act on the object to be disinfected in a short time, and a sufficient disinfection or sterilization cleaning effect can be obtained in 1 to 5 minutes.

  Hereinafter, the present invention will be described in detail with reference to Examples and Comparative Examples. In addition, "%" of each component in Table 1 means% (w / v) unless otherwise specified. Details of each component used in Examples and Comparative Examples are as follows.

・ Akamega wrinkle extract (Akamega wrinkle extract powder manufactured by Nippon Powder Chemical Co., Ltd.)
・ Keihi Extract (Keihi Extract manufactured by Nippon Powder Chemical Co., Ltd.)
・ St. John's wort extract (St. John's wort extract powder manufactured by Tokiwa Plant Chemical Laboratory Co., Ltd.)
-Mangosteen extract a (mangosteen aqua manufactured by Nippon Shinyaku Co., Ltd.)
・ Mangostin extract b (mangosteen α20 manufactured by Nippon Shinyaku Co., Ltd.)
-Garcinia extract (Gardenia powder J, manufactured by Nippon Shinyaku Co., Ltd.)
-Sugarcane extract (Mitsui Sugar Co., Ltd. product name sugarcane extract MSX-245)
-Perilla extract (Perilla extract powder RK manufactured by Nippon Shinyaku Co., Ltd.)
・ Huscup Extract (Hasscup Powder S, manufactured by Nippon Shinyaku Co., Ltd.)

<Examples 1 to 6 and Comparative Examples 1 to 4>
Each component was added to ion-exchanged water and mixed so that the components shown in Table 1 became 1.0% to prepare an anti-norovirus agent. Table 1 shows the pH of each of the obtained anti-norovirus agents.

<Evaluation of inactivation of norovirus>
Using each of the above-mentioned anti-norovirus agents, the inactivation of norovirus by the anti-norovirus agent was evaluated based on the method described in <Norovirus-HBGA binding inhibition assay as measurement of anti-norovirus effect>. The negative control was a case where PBS was allowed to act for 30 minutes instead of the anti-norovirus agent, and the binding inhibition rate (%) of the anti-norovirus agent with respect to the negative control was calculated and evaluated. The evaluation criteria are as follows. Table 1 shows the results.
++++: Binding inhibition rate of 90% or more (very high binding inhibition effect)
++: binding inhibition rate of 50% or more (high binding inhibition effect)
++: Binding inhibition rate of 30% or more +: Binding inhibition rate of less than 30% (no effect)

  As is evident from the results shown in Table 1, the anti-norovirus agent containing the red oak wrinkle extract, cayenne extract, St. John's wort extract, or mangosteen extract as an active ingredient shows a strong norovirus-HBGA binding inhibitory effect and excellent norovirus inactivity. It can be seen that the chemical effect is exhibited. Furthermore, the anti-norovirus agent containing the extract of Akameigawa and the extract of cinnamon showed a binding inhibitory effect close to 100% and exhibited a particularly excellent norovirus inactivating effect.

Claims (6)

  An anti-norovirus agent comprising, as an active ingredient, at least one selected from the group consisting of red wrinkle extract, cinnamon extract, St. John's wort extract, and mangosteen extract.   The anti-norovirus agent according to claim 1, wherein the content of the active ingredient is 0.01 to 10% (W / V).   3. The anti-norovirus agent according to claim 1, further comprising at least one of water and a polar organic solvent.   The anti-norovirus agent according to any one of claims 1 to 3, wherein the pH is in the range of 2 to 10.   A disinfectant comprising the anti-norovirus agent according to any one of claims 1 to 4.   A cleaning agent comprising the anti-norovirus agent according to any one of claims 1 to 4.