Anti-norovirus agents, disinfectants and cleaning agents
Patent Information
- Application Number
- JP2020169961
- Authority / Receiving Office
- JP · JP
- Patent Type
- Patents
- Current Assignee / Owner
- Priority Date
- 2019-10-07
- Filing Date
- 2020-10-07
- Publication Date
- 2025-02-25
- Estimated Expiration
- 2040-10-07
AI Technical Summary
【0015】 本発明によれば、植物由来であって、保存安定性に優れた抗ノロウイルス剤を提供することができる。さらに、本発明によれば、当該抗ノロウイルス剤を用いた消毒剤及び洗浄剤を提供することもできる。
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Abstract
Description
[Technical field]
[0001] The present invention relates to an anti-norovirus agent, a disinfectant, and a cleaning agent. [Background technology]
[0002] In recent years, cases of infectious gastroenteritis and food poisoning caused by norovirus have been occurring frequently throughout the year, with peak occurrences occurring from November to March. Norovirus is an envelopeless RNA virus classified in the Caliciviridae family and Norovirus genus, and is highly resistant to alcohol (ethanol, isopropanol, etc.), cationic soap, heat, acid (gastric acid, etc.), dryness, etc. The incubation period for norovirus 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.
[0003] Oral infection is known to be one of the routes of infection for norovirus, and infection occurs when food or water contaminated with the virus is orally ingested. Therefore, in places where food is prepared and processed, such as restaurants, food service facilities, and factories, it is necessary to take measures to prevent food, water, equipment, etc. from being contaminated by the norovirus.
[0004] Norovirus is so highly infectious that it can cause illness even with as few as 10 to 100 viruses. Therefore, there is a need for an anti-norovirus agent that acts directly on norovirus and reduces or eliminates its infectivity.
[0005] According to the Ministry of Health, Labor and Welfare, in order to inactivate norovirus, it is recommended to heat cooking utensils at 85°C for one minute and disinfect them with 200 ppm sodium hypochlorite (see Non-Patent Document 1). However, inactivating norovirus by heating has the problem of the heat resistance of the target object, and sodium hypochlorite is highly corrosive to metals, so its use may be restricted. Furthermore, in places with a lot of organic dirt such as kitchens, sodium hypochlorite may decompose and may not be sufficiently effective.
[0006] Furthermore, sodium hypochlorite is difficult to apply to the human body because of the risk of damaging the skin and mucous membranes, and it must be handled and used with care because it reacts with acid to generate toxic gases. Under these circumstances, there is a strong demand for an anti-norovirus agent that is easy to handle and can exert a sufficient inactivation effect even when sodium hypochlorite cannot be used.
[0007] As a method for inactivating norovirus and other viruses safely for the human body, the use of virus inactivating substances derived from plants is being investigated.
[0008] For example, Patent Document 1 describes a norovirus killing agent containing a specified amount of proanthocyanidins from grape seed extract. [Prior art documents] [Patent documents]
[0009] [Patent Document 1] JP 2013-47196 A [Non-patent literature]
[0010] [Non-Patent Document 1] Ministry of Health, Labor and Welfare website "Q&A about Norovirus"; https: / / www.mhlw.go.jp / stf / seisakunitsuite / bunya / kenkou_iryou / shokuhin / syokuchu / kanren / yobou / 040204-1.html#17 Summary of the Invention [Problem to be solved by the invention]
[0011] Various plant-derived anti-norovirus agents have been proposed, but they have the problem of poor storage stability.
[0012] The main object of the present invention is to provide an anti-norovirus agent that is derived from a plant and has excellent storage stability. Another object of the present invention is to provide a disinfectant and a cleaning agent that use the anti-norovirus agent. [Means for solving the problem]
[0013] The present inventors have conducted extensive research to solve the above problems. As a result, they have found that an anti-norovirus agent containing a plant-derived polyphenol in combination with a sulfur-containing reducing inorganic salt exhibits excellent anti-norovirus activity even after long-term storage. The present invention has been completed based on these findings and through further research.
[0014] That is, the present invention provides the following aspects. Item 1. An anti-norovirus agent comprising a plant-derived polyphenol and a sulfur-containing reducing inorganic salt. Item 2. The anti-norovirus agent according to Item 1, wherein the concentration of the plant-derived polyphenol is 0.001% by mass or more. Item 3. The anti-norovirus agent according to Item 1 or 2, wherein the concentration of the sulfur-containing reducing inorganic salt is 0.001% by mass or more. Item 4. The anti-norovirus agent according to any one of Items 1 to 3, wherein the plant-derived polyphenol is at least one of flavanols, gallotannins, ellagitannins, and phlorotannins. Item 5. The anti-norovirus agent according to any one of Items 1 to 4, wherein the sulfur-containing reducing inorganic salt is a sulfite. Item 6. The anti-norovirus agent according to any one of Items 1 to 5, further comprising an antioxidant. Item 7. The anti-norovirus agent according to Item 6, wherein the antioxidant is at least one of ascorbic acid and an ascorbate salt. Item 8. The anti-norovirus agent according to any one of Items 1 to 7, wherein the plant-derived polyphenol and the sulfur-containing reducing inorganic salt are contained in an aqueous ethanol solution having a concentration of 30% by mass or more. Item 9. A disinfectant comprising the anti-norovirus agent according to any one of items 1 to 8. Item 10. A cleaning agent comprising the anti-norovirus agent according to any one of items 1 to 8. Effect of the Invention
[0015] According to the present invention, it is possible to provide an anti-norovirus agent that is derived from a plant and has excellent storage stability. Furthermore, according to the present invention, it is also possible to provide a disinfectant and a cleaning agent that use the anti-norovirus agent. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0016] The anti-norovirus agent of the present invention, and the disinfectant and cleaning agent using the same will be described in detail below. In this specification, a numerical value connected with "~" means a numerical range including the numerical values before and after "~" as the lower limit and upper limit. When multiple lower limit values and multiple upper limit values are listed separately, any lower limit value and upper limit value can be selected and connected with "~".
[0017] The anti-norovirus agent of the present invention is characterized by containing a plant-derived polyphenol and a sulfur-containing reducing inorganic salt. Since the anti-norovirus agent of the present invention has such a composition, it is derived from a plant and exhibits excellent storage stability.
[0018] The anti-norovirus agent of the present invention contains a plant-derived polyphenol as an active ingredient. The plant-derived polyphenol exhibiting anti-norovirus activity can inactivate norovirus safely to the human body.
[0019] In the anti-norovirus agent of the present invention, the plant-derived polyphenol may be contained as a simple polyphenol or may be contained as a plant extract containing polyphenol and other components (other than polyphenol). That is, the anti-norovirus agent of the present invention may be an anti-norovirus agent containing a plant extract containing a plant-derived polyphenol and a sulfur-containing reducing inorganic salt.
[0020] The plant-derived polyphenol is not particularly limited as long as it exhibits anti-norovirus activity, and examples thereof include flavanols (e.g., proanthocyanidin, procyanidin, catechin, epicatechin, etc.), gallotannins (e.g., pentagalloylglucose, etc.), ellagitannins (e.g., pedunculagin, tellimagrandin I, casuarinin, tellimagrandin II, rugosin C, etc.), and phlorotannins (e.g., phloroglucinol, etc.). The plant-derived polyphenol contained in the anti-norovirus agent of the present invention may be one type or two or more types.
[0021] In the anti-norovirus agent of the present invention, preferred specific examples of the plant extract containing polyphenols include grape seed extract, apple extract (apple polyphenol), walnut extract (walnut polyphenol), mangosteen extract, peanut seed coat extract, Mallotus japonicus extract, lychee extract, pomegranate extract, evening primrose extract, persimmon tannin, cat's claw extract, seaweed extract, etc. These plant extracts contain polyphenols and exhibit anti-norovirus activity. The anti-norovirus agent of the present invention preferably contains at least one of grape seed extract, apple extract (apple polyphenol), walnut extract (walnut polyphenol), mangosteen extract, peanut seed coat extract, Mallotus japonicus extract, lychee extract, pomegranate extract, evening primrose extract, persimmon tannin, cat's claw extract, and seaweed extract.
[0022] Grape seed extract is not particularly limited as long as it contains proanthocyanidin. Grape seed extract is grape seed extract, and is grape seed extract (particularly contains polyphenol fraction). In the anti-norovirus agent of the present invention, proanthocyanidin can be suitably contained as grape seed extract.
[0023] Proanthocyanidins are polymers (condensed tannins) of flavanols (catechin, epicatechin, etc.). Most naturally occurring proanthocyanidins are procyanidins. More specifically, proanthocyanidins contained in grape seed extracts are mainly small amounts of procyanidins and their gallic acid esters, as represented by the following formula. In the following formula, n is preferably about 1 to 12 (i.e., about a dimer to a trimeric ester). In addition, 13 The average degree of polymerization measured by C-NMR analysis is preferably about 7 to 9. In addition, it is preferable that proanthocyanidins of each degree of polymerization have a gallic acid ester structure in a ratio of about one.
[0024] [ka]
[0025] Specific examples of grape seeds include seeds of plants of the genus Vitis in the family Vitaceae, such as European grape (Vitis vinifera), American grape (Vitis labrusca), and Amur grape (Vitis amurensis), and plants of the genus Muscadine, such as Muscadine (Muscadinia rotundifolia). The grape seed extract can be prepared by the method described in JP-A-11-80148, in which grape seeds are extracted with a water-soluble organic solvent (e.g., ethanol) or a mixture of a water-soluble organic solvent and water while heating and refluxing.
[0026] The grape seed extract may be extracted from the seeds of any variety of grapes, such as white grapes, red grapes, and black grapes, as long as it contains proanthocyanidins. For example, those obtained by organic solvent extraction or the like from grape seeds of various varieties, such as Chardonnay, Riesling, Koshu, Niagara, Neo Muscat, Kyoho, Delaware, Muscat Berry A, Shiraha (Ricattelli), Cereza, and Miratorgau, Vitis vinifera, Vitis vinifera hybrids, and non-Vitis vinifera hybrids, are preferably used. Commercially available grape seed extracts containing proanthocyanidins are easily available, such as those available under the trade names "Gravinol SE" (proanthocyanidin content of 83% by mass or more) and "Gravinol N" (proanthocyanidin content of 38% by mass or more) from Kikkoman Biochemifa Corporation, and "PPBHQ" (proanthocyanidin content of 70% by mass or more) from Began Trading Co., Ltd.
[0027] The content of proanthocyanidin in grape seed extract is not particularly limited, but is preferably 50% by mass or more, more preferably 60% by mass or more, even more preferably 70% by mass or more, and even more preferably 80% by mass or more.The upper limit of the content of proanthocyanidin in grape seed extract is, for example, about 95% by mass.
[0028] Apple polyphenol is an apple extract, for example an extract (polyphenol fraction) of apple skin, fruit, or a mixture thereof. In the anti-norovirus agent of the present invention, apple polyphenol can be suitably contained as apple extract.
[0029] Examples of the extracting solvent for apple extract 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; esters such as methyl acetate and ethyl acetate; ethers 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; polyethers such as polyethylene glycol; and organic solvents such as pyridines. These extracting solvents may be used alone or in combination of two or more. Among these, water, alcohol (e.g., ethanol), and water-containing alcohol (e.g., water-containing ethanol) are effective. That is, the apple extract is preferably a water extract, an alcohol extract, or a water-containing alcohol extract of apple. Only one type of apple extract may be used, or two or more types may be mixed and used.
[0030] Apple polyphenols are readily available as commercially available products. Examples of commercially available products include "Apple Polyphenol Powder" by Frontier Foods, Inc., "ApplePhenon (registered trademark) Apple Phenon SH" and "ApplePhenon (registered trademark) Apple Procyanidin" (procyanidin content of 18.4% by mass or more) by BGG Japan, Inc., "ApplePhenon (registered trademark) Apple Phenon C-100" by Access One, Inc., "Apple Polyphenol" (polyphenol content of 98.0% by mass) by Vidya Japan, Inc., and "Apple Extract Powder".
[0031] Components contained in apple polyphenols include procyanidins (condensed tannins), simple catechins such as (+)-catechin and (-)-epicatechin, phloridzin-series (chalcone) flavonoids, and phenolic acids mainly consisting of chlorogenic acid.
[0032] Walnut polyphenol is a polyphenol component contained in the seed coat (thin skin) of walnut (Juglans regia L.) In the anti-norovirus agent of the present invention, walnut polyphenol can be suitably contained as a walnut seed coat extract.
[0033] As the extraction solvent for walnut polyphenol, water, alcohol (e.g., ethanol), water-containing alcohol (e.g., water-containing ethanol), etc. are effective. That is, the walnut polyphenol is preferably a water extract, an alcohol extract, or a water-containing alcohol extract of walnut seed coat. Only one type of walnut polyphenol may be used, or two or more types may be mixed and used.
[0034] Walnut polyphenol is readily available as a commercially available product, such as walnut polyphenol-P10, walnut polyphenol-P30 (polyphenol content of 30.0% by mass or more), and walnut polyphenol-WSP10 (polyphenol content of 10.0% by mass or more) (all manufactured by Oryza Oil & Fat Chemical Co., Ltd.).
[0035] In addition, components known to be contained in walnut polyphenols include pedunculagin, tellimagrandin I, casuarinin, tellimagrandin II, and rugosin C.
[0036] Mangosteen extract is an extract from the peel of mangosteen (Garcinia mangostana).
[0037] As the extraction solvent for mangosteen extract, water, alcohol (e.g., ethanol), water-containing alcohol (e.g., water-containing ethanol), etc. are effective. That is, the mangosteen extract is preferably a water extract, an alcohol extract, or a water-containing alcohol extract of mangosteen peel, etc. One type of mangosteen extract may be used alone, or two or more types may be mixed and used.
[0038] Commercially available mangosteen extract products are readily available, such as Mangosteen α20 (polyphenol content of 20.0% by mass or more) and Mangosteen Aqua (both manufactured by Nippon Shinyaku Co., Ltd.).
[0039] Various polyphenols such as xanthones, procyanidins, and catechins are known to be contained in mangosteen extract.
[0040] Peanut husk extract is an extract of the husk of peanuts (Arachis hypogaea).
[0041] As the extraction solvent for the peanut seed coat extract, water, alcohol (e.g., ethanol), water-containing alcohol (e.g., water-containing ethanol), etc. are effective. That is, the peanut seed coat extract is preferably a water extract, an alcohol extract, or a water-containing alcohol extract of the peanut seed coat. Only one type of peanut seed coat extract may be used, or two or more types may be mixed and used.
[0042] Peanut seed coat extract is readily available as a commercially available product, such as peanut seed coat extract powder (proanthocyanidin content of 38.0% by mass or more) (manufactured by Tokiwa Yakuhin Phytochemical Laboratory Co., Ltd.).
[0043] Various polyphenols, such as proanthocyanidins, are known to be contained in peanut seed coat extract.
[0044] The Mallotus japonicus extract is an extract of the bark, leaves, roots, etc. of Mallotus japonicus, and is preferably an extract of the bark.
[0045] As the extracting solvent for Mallotus japonicus extract, water, alcohol (e.g., ethanol), water-containing alcohol (e.g., water-containing ethanol), etc. are effective. That is, the Mallotus japonicus extract is preferably a water extract, an alcohol extract, or a water-containing alcohol extract of Mallotus japonicus resin, leaves, roots, etc. Only one type of Mallotus japonicus extract may be used, or two or more types may be mixed and used.
[0046] Mallotus japonicus extract is readily available as a commercially available product, for example, Mallotus japonicus extract powder (polyphenol content of 14.0% by mass or more) (manufactured by Nippon Powder Pharmaceutical Co., Ltd.).
[0047] Various polyphenols are known to be contained in Mallotus japonicus extract, such as bergenin, geraniin, rutin, and corilagin.
[0048] Lychee extract is an extract of the seeds or fruit of lychee (Litchi chinensis).
[0049] As the extraction solvent for litchi extract, water, alcohol (e.g., ethanol), water-containing alcohol (e.g., water-containing ethanol), etc. are effective. That is, the litchi extract is preferably a water extract, an alcohol extract, or a water-containing alcohol extract of litchi seeds or fruits. Only one type of litchi extract may be used, or two or more types may be mixed and used.
[0050] Litchi extract is readily available as a commercially available product, such as Litchi Seed Extract-WSP (polyphenol content of 12.0% by mass or more) and Litchi Seed Extract-P (both manufactured by Oryza Oil & Fat Chemical Co., Ltd.).
[0051] Various polyphenols are known to be contained in lychee extract, such as flavonoids (leucocyanidin, saponin, tannin, anthocyanin (cyanidin glycoside, malvidin glycoside, etc.)
[0052] Pomegranate extract is an extract of the peel or flowers of the pomegranate (Punica granatum).
[0053] As the extraction solvent for pomegranate extract, water, alcohol (e.g., ethanol), water-containing alcohol (e.g., water-containing ethanol), etc. are effective. That is, the pomegranate extract is preferably a water extract, an alcohol extract, or a water-containing alcohol extract of the skin or flower of pomegranate. Only one type of pomegranate extract may be used, or two or more types may be mixed and used.
[0054] Commercially available pomegranate extract products are readily available, such as pomegranate peel extract powder and pomegranate flower extract powder (polyphenol content of 40.0% by mass or more) (both manufactured by Koei Kogyo Co., Ltd.).
[0055] Various polyphenols such as tannins and anthocyanins are known to be contained in pomegranate extract.
[0056] Evening primrose extract is an extract of the seeds of evening primrose (Oenothera tetraptera).
[0057] As the extracting solvent for the evening primrose extract, water, alcohol (e.g., ethanol), water-containing alcohol (e.g., water-containing ethanol), etc. are effective. That is, the evening primrose extract is preferably a water extract, an alcohol extract, or a water-containing alcohol extract of evening primrose seeds. Only one type of evening primrose extract may be used, or two or more types may be mixed and used.
[0058] Evening primrose extract is readily available as a commercially available product, such as Evening Primrose Extract-WSPS (polyphenol content of 50.0% by mass or more) and Evening Primrose Extract-P (polyphenol content of 60.0% by mass or more) (both manufactured by Oryza Oil & Fat Chemical Co., Ltd.).
[0059] Various polyphenols such as proanthocyanidins and pentagalloylglucose are known to be contained in evening primrose extract.
[0060] Persimmon tannin is an extract from the juice of persimmon (the fruit of the persimmon tree).
[0061] As the extraction solvent for persimmon tannin, water, alcohol (e.g., ethanol), water-containing alcohol (e.g., water-containing ethanol), etc. are effective. That is, persimmon tannin is preferably a water extract, an alcohol extract, or a water-containing alcohol extract of the juice of astringent persimmon. Only one type of persimmon tannin may be used, or two or more types may be mixed and used.
[0062] Persimmon tannin is readily available commercially, for example, persimmon tannin (tannin content of 3.0% by mass or more) (manufactured by Tomiyama Corporation).
[0063] Tannins are known to be contained in persimmons as polyphenols.
[0064] Cat's claw extract is an extract from the wood and bark of cat's claw (Uncaria tomentosa).
[0065] As the extraction solvent for cat's claw extract, water, alcohol (e.g., ethanol), water-containing alcohol (e.g., water-containing ethanol), etc. are effective. That is, the cat's claw extract is preferably a water extract, an alcohol extract, or a water-containing alcohol extract of the wood and bark of cat's claw. Only one type of cat's claw extract may be used, or two or more types may be mixed and used.
[0066] Cat's claw extract is readily available as a commercially available product, such as Cat's Claw Extract Powder (Nihon Funwa Yakuhin Co., Ltd.) or Bizen Cat's Claw Extract Powder (Bizen Kasei Co., Ltd.).
[0067] Various polyphenols such as proanthocyanidins and catechins are known to be contained in cat's claw extract.
[0068] Seaweed polyphenols are extracts of Ascophyllum nodosum, a member of the Fucus family.
[0069] As the extraction solvent for Ascophyllum nodosum, water, alcohol (e.g., ethanol), water-containing alcohol (e.g., water-containing ethanol), etc. are effective. That is, the seaweed polyphenol is preferably a water extract, an alcohol extract, or a water-containing alcohol extract of Ascophyllum nodosum. Only one type of seaweed polyphenol may be used, or two or more types may be mixed and used.
[0070] Seaweed polyphenols are readily available as commercial products, such as Seaweed Polyphenol (polyphenol content of 75.0% by mass or more) (manufactured by Riken Vitamin Co., Ltd.).
[0071] Phloroglucinol is known to be one of the polyphenols contained in seaweed polyphenols.
[0072] In the anti-norovirus agent of the present invention, the concentration of the plant-derived polyphenol (content, meaning the total content if there are multiple types) is preferably 0.001% by mass or more, more preferably 0.005% by mass or more, and even more preferably 0.008% by mass or more. The upper limit of the concentration of the plant-derived polyphenol is not particularly limited, but is preferably 0.80% by mass or less, more preferably 0.50% by mass or less, and even more preferably 0.30% by mass or less. When grape seed extract, apple polyphenol, walnut polyphenol, mangosteen extract, peanut seed coat extract, Mallotus japonicus extract, lychee extract, pomegranate extract, evening primrose extract, or cat's claw extract is used as the plant-derived polyphenol, the concentration of these (content, meaning the total content if there are multiple types) is preferably about 0.001 to 0.50% by mass, more preferably about 0.005 to 0.10% by mass, and even more preferably about 0.008 to 0.08% by mass. Furthermore, when persimmon tannin or seaweed polyphenols are used as plant-derived polyphenols, their concentration (content, meaning the total content if multiple types are used) is preferably about 0.001 to 1.0 mass%, more preferably about 0.005 to 0.50 mass%, and even more preferably about 0.01 to 0.30 mass%.
[0073] The sulfur-containing reducing inorganic salt is a reducing inorganic salt containing sulfur. The anti-norovirus agent of the present invention contains a sulfur-containing reducing inorganic salt in addition to a plant-derived polyphenol having anti-norovirus activity, and thus the storage stability of the anti-norovirus agent is improved. More specifically, the storage stability of the anti-norovirus agent of the present invention means that the decrease in activity of the anti-norovirus agent over time is suppressed.
[0074] The sulfur-containing reducing inorganic salt is not particularly limited, but is preferably a sulfite. Specific examples of the sulfite include sulfites such as sodium sulfite and potassium sulfite; pyrosulfites such as sodium pyrosulfite and potassium pyrosulfite; and hydrogen sulfites such as sodium hydrogen sulfite and potassium hydrogen sulfite. The sulfur-containing reducing inorganic salt contained in the anti-norovirus agent of the present invention may be one type or two or more types.
[0075] In the anti-norovirus agent of the present invention, the concentration (content) of the sulfur-containing reducing inorganic salt is preferably 0.001% by mass or more, more preferably 0.005% by mass or more, and even more preferably 0.008% by mass or more. The upper limit of the concentration of the sulfur-containing reducing inorganic salt is not particularly limited, and may be, for example, 1.0% by mass or less, preferably 0.80% by mass or less, more preferably 0.50% by mass or less, and even more preferably 0.30% by mass or less.
[0076] The viruses that the anti-norovirus agent of the present invention inactivates are at least one of human norovirus (HNV), feline calicivirus (FCV), and murine norovirus (MNV), with human norovirus being a particularly suitable target for inactivation.
[0077] From the viewpoint of further enhancing the storage stability, the anti-norovirus agent of the present invention preferably further contains an antioxidant in addition to the plant-derived polyphenol and the sulfur-containing reducing inorganic salt.
[0078] Specific examples of antioxidants include ascorbic acid or ascorbic acid salts (specifically, L-ascorbic acid, L-ascorbic acid salts (e.g., sodium salts, potassium salts, and other metal salts), D-ascorbic acid, D-ascorbic acid salts (e.g., sodium salts, potassium salts, and other metal salts), L-ascorbic acid phosphate Mg, L-ascorbic acid palmitate, L-ascorbic acid 2-glucoside, and the like), L-cysteine, N-acetyl L-cysteine, cystine, glutathione (oxidized form), glutathione (reduced form), L-methionine, L-ergothioneine, thioctic acid, trans-ferulic acid, edetate, propyl gallate, tocopherol, dibutylhydroxytoluene, butylhydroxyanisole, sulfur dioxide, chlorogenic acid, catechin, and epicatechin. The antioxidants contained in the anti-norovirus agent of the present invention may be one type or two or more types.
[0079] As the antioxidant for the anti-norovirus agent, L-ascorbic acid, L-ascorbate salts, etc., as exemplified above, are generally used, and in the anti-norovirus agent of the present invention, they can be suitably used in combination with plant-derived polyphenols and sulfur-containing reducing inorganic salts. The storage stability of the anti-norovirus agent of the present invention is suitably improved compared to anti-norovirus agents using plant-derived polyphenols and antioxidants such as L-ascorbic acid and L-ascorbate salts instead of sulfur-containing reducing inorganic salts. In the present invention, the storage stability of the anti-norovirus agent is effectively improved by using the sulfur-containing reducing inorganic salts. In addition, the coloring of the anti-norovirus agent due to oxidation can be significantly suppressed.
[0080] Furthermore, when the anti-norovirus agent of the present invention contains an antioxidant, the concentration thereof is not particularly limited as long as it does not inhibit the effects of the present invention, and is preferably about 0.001 to 0.50 mass%, more preferably 0.003 to 0.05 mass%, and even more preferably 0.005 to 0.03 mass%.
[0081] 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 plant-derived polyphenol and the sulfur-containing reducing inorganic salt.
[0082] The polar organic solvent is not particularly limited as long as it does not inhibit the effects of the present invention, but a lower alcohol such as ethanol or isopropanol is preferred, and ethanol is more preferred. In addition, the anti-norovirus agent of the present invention preferably contains an ethanol aqueous solution. That is, it is particularly preferred that the anti-norovirus agent of the present invention contains a plant-derived polyphenol and a sulfur-containing reducing inorganic salt in an ethanol aqueous solution.
[0083] For example, when the anti-norovirus agent of the present invention is used as a disinfectant or cleaning agent, the lower limit of the ethanol concentration in the aqueous ethanol solution is about 30% by mass or more, and the optimum range is about 30% by mass to about 80% by mass.
[0084] From the viewpoint of enhancing the inactivation effect against norovirus, the pH of the anti-norovirus agent of the present invention is preferably in the range of 2.0 to 10.0, and more preferably in the range of 2.5 to 7.0.
[0085] The pH of the anti-norovirus agent of the present invention can be adjusted using a known pH adjuster or buffer solution. Examples of pH adjusters include inorganic acids such as hydrochloric acid, nitric acid, sulfuric acid, and phosphoric acid; organic acids such as acetic acid, malic acid, citric acid, lactic acid, fumaric acid, succinic acid, tartaric acid, gluconic acid, phosphoric acid, benzoic acid, sorbic acid, adipic acid, cinnamic acid, itaconic acid, and phytic acid, and their salts (which may be the same as or different from the above-mentioned organic acids and organic acid salts); alkali metal hydroxides such as sodium hydroxide and potassium hydroxide; and carbonates such as potassium carbonate and sodium hydrogen carbonate. Examples of buffer solutions include phosphate buffer, citrate phosphate buffer, and lactate buffer.
[0086] The anti-norovirus agent of the present invention may contain an additive. The additive is not particularly limited, and additives that can be used in known anti-virus agents can also be used in the present invention. Examples of additives include amino acids. Only one type of additive may be used, or two or more types may be mixed and used. When the anti-norovirus agent of the present invention contains an additive, the concentration of the additive is not particularly limited as long as it does not inhibit the effects of the present invention, and may be, for example, about 0.001 to 4.0% by mass.
[0087] Examples of amino acids include L-phenylalanine, L-methionine, L-isoleucine, L-alanine, DL-alanine, L-serine, L-arginine, L-lysine, L-valine, L-glycine, L-theanine, L-threonine, L-proline, L-histidine, L-glutamine, L-glutamic acid, L-leucine, L-tryptophan, L-ornithine, L-citrulline, L-tyrosine, L-carnitine, and salts thereof. By including an amino acid, the pH of the anti-norovirus agent of the present invention can be adjusted, and coloring due to oxidation can be suppressed.
[0088] The anti-norovirus agent of the present invention may also contain general antiviral components such as acyclovir, and general antibacterial components such as phenoxyethanol, chlorhexidine gluconate, benzalkonium chloride, benzethonium chloride, cetylpyridinium chloride, alkyldiaminoethylglycine hydrochloride, and isopropylmethylphenol, as long as the characteristics of the present invention are not impaired.
[0089] In addition, even if glycerin fatty acid ester is added to enhance the disinfecting power against general bacteria, it does not affect the inactivation action against norovirus, so there is no problem. Examples of glycerin fatty acid ester include glycerin monocaprate, glycerin monolaurate, glycerin monomyristate, glycerin monopalmitate, glycerin monostearate, glycerin monoisostearate, glycerin monooleate, and glycerin monobehenate; glycerin difatty acid ester such as glycerin distearate, glycerin diisostearate, and glycerin dioleate; and monoglyceride derivatives such as acetate monoglyceride, citrate monoglyceride, succinate monoglyceride, diacetyltartarate monoglyceride, and lactate monoglyceride. In the present invention, one or more of these can be selected and used. In terms of enhancing the disinfecting power against general bacteria, it is preferable to use glycerin monofatty acid esters of fatty acids having 8 to 12 carbon atoms, such as glycerin monocaprylic acid ester, glycerin monocapric acid ester, and glycerin monolauric acid ester.
[0090] Furthermore, surfactants other than the above-mentioned glycerol fatty acid esters can be added to the anti-norovirus agent of the present invention for the purpose of imparting cleaning properties and foaming properties, within a range that does not affect the inactivation of norovirus or the stability of the composition, etc. Examples of such surfactants that can be used include cationic surfactants such as primary to tertiary fatty amine salts, quaternary ammonium salts, and 2-alkyl-1-alkyl-1-hydroxyethyl imidazolinium salts; alkyl betaine-type surfactants such as N,N-dimethyl-N-alkyl-N-carboxymethyl ammonium betaine; amino carboxylic acid-type surfactants such as N,N-dialkyl amino alkylene carboxylic acid; alkyl sulfobetaine-type surfactants such as N,N,N-trialkyl-N-sulfo alkylene ammonium betaine; and imidazoline-type amphoteric surfactants such as 2-alkyl-1-hydroxyethyl-1-carboxymethyl imidazolinium betaine. Furthermore, for the purposes of increasing foaming, improving the stability of the formulation, flavoring, etc., water-soluble polymers such as gum arabic, carrageenan, sodium carboxymethylcellulose, hydroxycellulose, sodium polyacrylate, etc.; sequestering agents such as sodium ethylenediaminetetraacetate, tripolyphosphate, hexametaphosphate, etc.; inorganic salts such as sodium chloride, potassium chloride, sodium sulfate, etc.; flavorings, etc. may be added.
[0091] The anti-norovirus agent of the present invention can be used as a disinfectant or cleaner (germicidal cleaner) as it is or by adding various carriers, other surfactants, bactericides, and other additives. That is, the disinfectant and cleaner of the present invention each contain the anti-norovirus agent of the present invention.
[0092] The disinfectant or cleaner of the present invention can be provided in various forms such as liquid, gel, powder, etc., but in order to act on a wide range of disinfection objects in a short time, it is preferable to provide it in the form of a liquid or a sheet impregnated with a liquid. The liquid disinfectant or cleaner can be provided as a lotion, spray, etc., and can be filled into a bottle with a measuring cap, a trigger type spray container, a squeeze type or dispenser type pump spray container, etc., and used by scattering or spraying. The liquid-impregnated sheet disinfectant or cleaner, or the liquid of the disinfectant or cleaner can be impregnated into paper, cloth, etc., and filled into a container such as a bottle or bucket, and provided as a wet sheet.
[0093] The disinfectant or cleaning agent of the present invention can be widely used for disinfecting, sterilizing and cleaning facilities such as hospital rooms, rooms, kitchens, bathrooms, washrooms and toilets, and for disinfecting, sterilizing and cleaning furniture such as tables, chairs and bedding, and instruments, devices and equipment such as tableware, cooking utensils and medical supplies, and for disinfecting, sterilizing and cleaning places where norovirus may be present or objects that may be contaminated with norovirus.
[0094] The disinfectant or cleaner of the present invention may be used in an amount sufficient to thoroughly wet the surface of the object to be disinfected. The disinfectant or cleaner of the present invention may be allowed to act on the object to be disinfected for a short period of time, and sufficient disinfection or germicidal cleaning effect can be obtained in 1 to 5 minutes. EXAMPLES
[0095] The present invention will be described in detail below with reference to examples and comparative examples. The numerical values of each component in the table mean mass % unless otherwise specified. Details of each component used in the examples and comparative examples are as follows.
[0096] Grape seed extract: Kikkoman Biochemifa Corporation's product name "Gravinor SE" (active ingredient concentration 100%) Apple polyphenol: BGG Japan Co., Ltd.'s product name "ApplePhenon (registered trademark) Applephenon SH" (active ingredient concentration 100%) Walnut polyphenol: Oryza Oil & Fat Chemical Co., Ltd.'s product name "Walnut Polyphenol-P30" (active ingredient concentration 90%) Mangosteen extract: Nippon Shinyaku Co., Ltd.'s product name "Mangosteen α20" (active ingredient concentration 100%) Peanut seed coat extract: "Peanut seed coat extract powder" (active ingredient concentration 100%) manufactured by Tokiwa Phytochemical Laboratory Co., Ltd. Mallotus japonicus Extract: Product name "Mallotus japonicus Extract Powder" manufactured by Nippon Powder Pharmaceutical Co., Ltd. (active ingredient concentration 100%) Lychee extract: Oryza Oil & Fat Chemical Co., Ltd.'s product name "Lychee Seed Extract-WSP" (active ingredient concentration 100%) Pomegranate extract: Product name "Pomegranate peel extract powder" by Koei Kogyo Co., Ltd. (active ingredient concentration 100%) Evening primrose extract: Oryza Oil & Fat Chemical Co., Ltd.'s product name "Evening primrose extract-WSPS" (active ingredient concentration 100%) Persimmon tannin: Tomiyama Co., Ltd.'s product name "Persimmon tannin" (active ingredient concentration 100%) Cat's Claw Extract: Nippon Powder Pharmaceutical Co., Ltd.'s product name "Cat's Claw Extract Powder" (active ingredient concentration 66%) Seaweed polyphenol: Riken Vitamin Co., Ltd.'s product name "Seaweed polyphenol" (active ingredient concentration 100%) (extract of Ascophyllum nodosum) Sodium sulfite: Sodium sulfite (effective concentration 100%), a product of Shinshu Chemical Co., Ltd. Potassium pyrosulfite: Potassium pyrosulfite (effective concentration 100%), a product of Shinshu Chemical Co., Ltd. · L-Ascorbic acid: "Vitamin C" product by Fuso Chemical Co., Ltd. (effective concentration 100%) · Sodium L-ascorbate: Fujifilm Wako Pure Chemical Corporation's product "Sodium L(+)-ascorbate" (effective concentration 100%) D-Ascorbic acid: Sodium isoascorbate monohydrate (effective concentration 100%), a product of Fujifilm Wako Pure Chemical Corporation · L-cysteine hydrochloride: Fujifilm Wako Pure Chemical Corporation's product "L-cysteine hydrochloride monohydrate" (effective concentration 100%) · trans-Ferulic acid: Fujifilm Wako Pure Chemical Corporation's product "(E)-Ferulic acid" (effective concentration 100%) Citric acid: "Purified citric acid (crystals)" (effective concentration 100%), a product of Fuso Chemical Co., Ltd. Sodium citrate: "Purified sodium citrate" (effective concentration 100%), a product of Fuso Chemical Co., Ltd. Lactic acid: Fermented lactic acid (effective concentration 88%), a product of CSM Japan Co., Ltd. Sodium lactate: "Fermented sodium lactate" (effective concentration 50%), a product of CSM Japan Co., Ltd.
[0097] <Examples 1 to 31 and Comparative Examples 1 to 16> The components were mixed to obtain the compositions shown in Tables 1 to 12, respectively, to prepare anti-norovirus agents.
[0098] <Norovirus inactivation evaluation> Using each of the norovirus agents obtained in Examples 1 to 31 and Comparative Examples 1 to 16, the disappearance of human norovirus (HNV) genes was confirmed by the following procedure, and the inactivation of norovirus was evaluated. Each anti-norovirus agent was used after it was prepared and stored in a 40°C environment for 2 weeks, 3 weeks, 4 weeks, 6 weeks, 8 weeks, or 10 weeks, or after it was stored in a 50°C environment for 2 weeks or 4 weeks. As for the storage environment conditions of the samples, 100 g of each sample was placed in a PP sampler bottle (100 mL) manufactured by Sanplatec Co., Ltd., and stored at a predetermined temperature in a high-temperature incubator (TVN680TA) manufactured by ADVANTEC. The results are shown in Tables 1 to 12. The effect of each norovirus agent against norovirus was examined by RT-PCR as follows. Since norovirus cannot be cultured in a laboratory, a norovirus sample roughly purified from the feces of a norovirus patient was diluted 10-fold with PBS to prepare a test norovirus solution, and 900 μL of the sample solution and 100 μL of the virus solution were mixed and allowed to act on a rotator for 1 minute. Immediately after that, 140 μL of the working solution was collected, and viral RNA was extracted using QIAGEN's QIAamp (registered trademark) Viral RNA Mini kit. cDNA was obtained from the extracted viral RNA using random hexamers and reverse transcriptase. PCR was performed using the obtained cDNA as a template and G2-SKF (CNTGGGAGGGCGATCGCAA: sequence number 3) and G2-SKR (CCRCCNGCATRHCCRTTRTACAT: sequence number 4) as primers. The primers were referenced in Figure 3 and Table 11 in the appendix to Food Safety Inspection No. 0514004 dated May 14, 2007, "Method of detecting norovirus." It is also possible to use other primers as long as they can detect the norovirus gene. The PCR products obtained were separated by agarose gel electrophoresis to detect the viral gene. ○: The band derived from the human norovirus (HNV) gene has disappeared, and the antibody has an inactivating effect against HNV. ×: The band derived from the human norovirus (HNV) gene did not disappear, and there was no inactivation effect against HNV.
[0099]
Table 1
[0100]
Table 2
[0101]
Table 3
[0102]
Table 4
[0103]
Table 5
[0104]
Table 6
[0105]
Table 7
[0106]
Table 8
[0107]
Table 9
[0108]
Table 10
[0109]
Table 11
[0110] [Table 12]
[0111] In Tables 1 to 12, the units of the composition of the anti-norovirus agent are mass %. The concentrations of each component are the concentrations of the active ingredient. In the item of the presence or absence of HNV electrophoretic gene loss in Tables 1 to 12, "-" means that the evaluation was not performed.
[0112] As is clear from the results shown in Tables 1 to 12, it is found that the anti-norovirus agent containing a plant-derived polyphenol and a sulfur-containing reducing inorganic salt has an excellent anti-norovirus effect.
Claims
1. Plant-derived polyphenols (excluding persimmon tannins) and sulfur-containing reducing inorganic salts, The anti-norovirus agent, wherein the sulfur-containing reducing inorganic salt is a sulfite.
2. The anti-norovirus agent according to claim 1 , wherein the concentration of the plant-derived polyphenol is 0.001% by mass or more.
3. The anti-norovirus agent according to claim 1 or 2, wherein the concentration of the sulfur-containing reducing inorganic salt is 0.001% by mass or more.
4. The anti-norovirus agent according to any one of claims 1 to 3, wherein the plant-derived polyphenol is at least one of flavanols, gallotannins, ellagitannins, and phlorotannins.
5. The anti-norovirus agent according to any one of claims 1 to 4, further comprising an antioxidant.
6. The anti-norovirus agent according to claim 5 , wherein the antioxidant is at least one of ascorbic acid and an ascorbate salt.
7. The anti-norovirus agent according to any one of claims 1 to 6, wherein the plant-derived polyphenol and the sulfur-containing reducing inorganic salt are contained in an aqueous ethanol solution having a concentration of 30 mass% or more.
8. A disinfectant for use in a facility, comprising the anti-norovirus agent according to any one of claims 1 to 7.
9. A cleaning agent for instruments, equipment, or devices, comprising the anti-norovirus agent according to any one of claims 1 to 7.
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