WO2013012007A1 - Anti-virus agent composition - Google Patents
Anti-virus agent composition Download PDFInfo
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- WO2013012007A1 WO2013012007A1 PCT/JP2012/068213 JP2012068213W WO2013012007A1 WO 2013012007 A1 WO2013012007 A1 WO 2013012007A1 JP 2012068213 W JP2012068213 W JP 2012068213W WO 2013012007 A1 WO2013012007 A1 WO 2013012007A1
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- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N33/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic nitrogen compounds
- A01N33/02—Amines; Quaternary ammonium compounds
- A01N33/12—Quaternary ammonium compounds
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/13—Amines
- A61K31/14—Quaternary ammonium compounds, e.g. edrophonium, choline
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/02—Local antiseptics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Definitions
- the present invention relates to an antiviral composition having a virus inactivating effect.
- Viral infectious diseases such as influenza and colds are considered to be one of the important preventive measures to clean fingers and the environment.
- viral acute gastroenteritis and diarrhea are not only confirmed as outbreaks in nursing homes, schools, hospitals, etc., but also outbreaks due to food poisoning through contaminated food in restaurants, cooking facilities, etc.
- These causative viruses include non-enveloped viruses such as norovirus, sapovirus, and rotavirus, and infection of children and the elderly may cause serious symptoms.
- hand-foot-and-mouth disease which is a typical pediatric infection
- foot-and-mouth disease-causing viruses that cause tremendous damage to livestock are also classified as non-enveloped viruses. is there.
- norovirus has been detected not only in Japan but around the world as a causative virus for non-bacterial food poisoning and acute gastroenteritis.
- bacteria such as Staphylococcus aureus and Bacillus cereus have been conventionally known.
- food poisoning caused by norovirus causing acute gastroenteritis is about 25% of the number of food poisoning cases, and the number of patients is about about the whole. It accounts for half, is the largest, and is regarded as a problem as a virus that causes mass infection.
- the infection route is well-known for oral infection caused by eating shellfish such as raw oysters.
- Norovirus is an RNA virus that does not have an envelope (membrane-like structure) classified in the Caliciviridae and Norovirus genus, has a strong resistance to acid (gastric acid), and a small amount (about 10 to 100). It is known to be infected with. At present, there are no vaccines or treatments for norovirus, and the only treatment is to prevent norovirus infection by eliminating viruses or inactivating the virus by cleaning or disinfecting food, cooking utensils, and fingers that may cause it. Is the law. However, since norovirus has strong physicochemical resistance, ethanol and disinfectants including cationic surfactants that are effective against many bacteria are effective against norovirus in general usage. You may not get.
- disinfectants such as chlorine bleach (sodium hypochlorite, etc.), iodine agents (povidone iodine, etc.), aldehyde agents (glutaral, etc.) and peracetic acid preparations are used for inactivating norovirus.
- disinfectants are highly irritating to humans and corrode metals.
- chlorine-based bleaching agent has the effect of bleaching the color pattern of the fiber, and there is a limit in use for textile products and clothing. For this reason, in consideration of the safety of the user, the object to be used, and the usage scene, there are limitations on using these drugs in living environments, fingers, cooking utensils, clothing, and the like.
- a composition containing a lower alcohol, an alkaline substance and a cationic surfactant (Patent Document 1) , A composition containing hydrogen peroxide, benzyl alcohol and a silver component (Patent Document 2), a composition containing a specific amine and / or a quaternary ammonium salt and a specific alkanolamine (Patent Document 3), A composition having a quaternary ammonium salt as an active ingredient and a pH of 5 to 9 (Patent Document 4) or a composition containing a plant extract containing a natural product tannin as an active ingredient (Patent Document 5) has been reported. Yes.
- the present invention relates to the following 1) to 5).
- a method for enhancing the activation effect (A) Combined with the quaternary ammonium salt of (A) above to enhance the virus inactivating effect of one or more quaternary ammonium salts selected from dialkyldimethylammonium salts and alkylbenzyldimethylammonium salts (B) Use of benzyl alcohol.
- the present invention relates to providing an antiviral composition which has little irritation and corrosivity and has a virus inactivating effect, particularly an excellent inactivating effect against non-enveloped viruses such as Norovirus.
- the present inventors have examined components effective for preventing infection of non-enveloped viruses such as Norovirus. When a specific quaternary ammonium salt and benzyl alcohol are used in combination, the quaternary ammonium salt is used. It was found that the virus inactivating effect was greatly increased as compared with the case of using alone, and it was useful as an antiviral composition.
- the composition of the present invention has an excellent antiviral action against non-enveloped viruses such as Norovirus, and is less irritating and corrosive, so that it can be used safely and for a short time.
- non-enveloped viruses such as Norovirus
- it is possible to inactivate the virus attached to floors and walls of large-scale cooking facilities, kitchen spaces, etc., medical equipment, food processing equipment, cooking utensils and the like.
- it can be effectively used to inactivate viruses and disinfect hands and fingers attached to floors, walls, furniture, and the like in the dwellings of ordinary households.
- Dialkyldimethylammonium salt and alkylbenzyldimethylammonium salt which are quaternary ammonium salts of component (A), are known compounds as antibacterial cationic surfactants. These may be used alone or in combination of two or more.
- the dialkyldimethylammonium salt and the alkylbenzyldimethylammonium salt preferably include a dialkyl (C 8-18 ) dimethylammonium salt and an alkyl (C 12-16 ) benzyldimethylammonium salt, respectively.
- the alkyl group in the dialkyldimethylammonium salt includes an alkyl group having 8 to 18 carbon atoms, preferably a linear alkyl group having 8 to 18 carbon atoms.
- Specific examples include octyl, decyl, dodecyl (lauryl), tetradecyl (myristyl), hexadecyl (cetyl), heptadecyl, octadecyl (stearyl), and more preferably octyl, decyl, and dodecyl.
- the alkyl group in the alkylbenzyldimethylammonium salt includes an alkyl group having 12 to 16 carbon atoms, preferably a linear alkyl group having 12 to 16 carbon atoms. Specific examples include dodecyl (lauryl), tetradecyl (myristyl), and hexadecyl (cetyl).
- Suitable dialkyldimethylammonium salts include didecyldimethylammonium salts, and alkylbenzyldimethylammonium salts include dodecylbenzyldimethylammonium salts, tetradecylbenzyldimethylammonium salts, and hexadecylbenzyldimethylammonium salts.
- Ammonium salts include salts with halide ions such as F ⁇ , Cl ⁇ , Br ⁇ and I ⁇ , NO 3 ⁇ , SO 4 2 ⁇ , etc., and salts with halide ions are preferred and chlorides. More preferred are salts with ions.
- More preferable quaternary ammonium salts include dodecylbenzyldimethylammonium chloride, tetradecylbenzyldimethylammonium chloride, hexadecylbenzyldimethylammonium chloride, and didecyldimethylammonium chloride.
- the quaternary ammonium salt of the present invention can be produced by a known method, and a commercially available product can also be used.
- Cotamin D10P manufactured by Kao Corporation
- Sanizol 08 manufactured by Kao Corporation
- Sanisole C manufactured by Kao Corporation
- the quaternary ammonium salt alone has an inactivating effect against norovirus (by an alternative experiment with feline calicivirus (FCV)) at a contact time of about 60 minutes alone, but the effect is insufficient in a short time. There is no significant inactivation effect unless used for a long time or at a high concentration.
- the component (B) benzyl alcohol can be used by purchasing a commercial product.
- a commercial product For example, products from Kanto Chemical Co., Inc. or Tokyo Chemical Industry Co., Ltd. can be purchased and used.
- other organic solvents can be mixed and used with benzyl alcohol as long as the antiviral effect is not affected.
- composition of the present invention containing the above (A) quaternary ammonium salt and (B) benzyl alcohol, the antiviral activity of the quaternary ammonium salt against norovirus (by an alternative experiment with feline calicivirus (FCV)) is remarkably increased.
- FCV feline calicivirus
- composition of the present invention may be any composition that exhibits a virus inactivation effect that removes or significantly reduces the ability to infect or proliferate viruses, and may denature or disrupt virus particles and nucleic acids (RNA). As a result, it may be possible to reduce or inhibit the ability of the virus to infect or proliferate by adsorption to the surface of the virus or host cell, binding of the virus with an enzyme, or the like.
- RNA nucleic acids
- the “virus” is preferably a non-enveloped virus, that is, a single-stranded (+) RNA virus having no envelope, a single-stranded ( ⁇ ) RNA virus, a double-stranded RNA virus, a single-stranded virus.
- a non-enveloped virus that is, a single-stranded (+) RNA virus having no envelope, a single-stranded ( ⁇ ) RNA virus, a double-stranded RNA virus, a single-stranded virus.
- viruses include DNA viruses and double-stranded DNA viruses. Examples of such viruses include viruses belonging to the Caliciviridae, Picornaviridae, Parvoviridae, Papillomaviridae, Polyomaviridae, and Adenoviridae families.
- the composition of the present invention is excellent in inactivating effect against Caliciviridae virus (single-stranded (+) virus), and among the Caliciviridae viruses, the genera Besivirus, Norovirus and Sapovirus It has an excellent inactivation effect on viruses belonging to the group, and in particular has an excellent inactivation effect on viruses belonging to the genus Besivirus and Norovirus.
- the mass ratio of the components (A) and (B) is such that (A) / (B) is 3/1 to 1/500, more preferably 3/1 to 1/40, and further 2/1 to 1/10 is preferable.
- composition of the present invention comprises only other components (A) and (B) or, if necessary, other components such as a chelating agent in order to further improve the antiviral activity and maintain the effect.
- a chelating agent in order to further improve the antiviral activity and maintain the effect.
- products and preparations used for cleaning of floors and walls of large-scale cooking facilities, kitchen spaces, medical equipment, food processing equipment, cooking utensils, and various living environments Providing antiviral activity to products and preparations used in foods (eg kitchen detergents, faucet care agents, bath detergents, toilet cleaners, floor and furniture cleaning products, etc.) and clothes and textile products Can be used as a material for.
- the chelating agent (1) tripolyphosphoric acid, pyrophosphoric acid, orthophosphoric acid, hexametaphosphoric acid and alkali metal salts thereof, (2) ethylenediaminetetraacetic acid, hydroxyiminodiacetic acid, dihydroxyethylglycine, nitrilotriacetic acid, hydroxyethylenediamine Triacetic acid, diethylenetriaminepentaacetic acid, triethylenetetraminehexaacetic acid and alkali metal salts or alkaline earth metal salts thereof, (3) aminotrimethylenephosphonic acid, 1-hydroxyethylidene-1,1-diphosphonic acid, ethylenediaminetetramethylenephosphone Acid, diethylenetriaminepentamethylenephosphonic acid, N-oxide of aminotrimethylenephosphonic acid and alkali metal salts or alkaline earth metal salts thereof, (4) acrylic acid and methacrylic acid?
- composition of the present invention may further contain, for example, additives such as oil, higher fatty acids, silicones, pH adjusters, thickeners, suspending agents, powder components, natural extracts, pigments, and fragrances as appropriate. It can be used to produce an antiviral composition that is blended and stirred and dispersed or dissolved.
- additives such as oil, higher fatty acids, silicones, pH adjusters, thickeners, suspending agents, powder components, natural extracts, pigments, and fragrances as appropriate. It can be used to produce an antiviral composition that is blended and stirred and dispersed or dissolved.
- acid agents such as inorganic acids such as hydrochloric acid and sulfuric acid, organic acids such as citric acid, succinic acid, malic acid, fumaric acid, tartaric acid, malonic acid, maleic acid, sodium hydroxide and water
- Alkaline agents such as sodium carbonate and potassium carbonate such as potassium oxide, ammonia and derivatives thereof, amine salts such as monoethanolamine, diethanolamine, and triethanolamine may be used alone or in combination.
- these acid agents and alkali agents may be used in combination as a buffer system.
- the above composition is preferably adjusted to have a pH of 2 to 12 at 20 ° C. with the above pH adjuster, and particularly to have a pH of 4 to 11 in terms of effects on humans and substrates. To preferred.
- the content of the quaternary ammonium salt of the component (A) in the composition of the present invention is 0.05 vol% or more and 0.5 vol% or less, more preferably 0.1 vol% or more from the viewpoint of antiviral activity. More preferably, it is 0.2 vol% or more, and 0.5 vol% or less, 0.2 vol% or less, or 0.1 vol% or less is mentioned from the viewpoint of blending into a product or the like. For example, 0.05 to 0.5 vol%, 0.1 to 0.5 vol%, 0.2 to 0.5 vol%, 0.05 to 0.2 vol%, 0.05 to 0.1 vol%, 0.1 to 0.2 vol% etc. are mentioned.
- the content of benzyl alcohol as component (B) is 0.5 to 2 vol%, but from the viewpoint of antiviral activity, it is more preferably 1 vol% or more, and even more preferably 1.5 vol% or more. From the viewpoint of property and blending, 2 vol% or less, 1.5 vol% or less, or 1.0 vol% or less can be mentioned. Examples thereof include 0.5 to 2 vol%, 0.5 to 1 vol%, 0.5 to 1.5 vol%, and 1 to 2 vol%.
- the composition of the present invention is a place where there is a risk of virus attachment, for example, kitchen (kitchen floor, kitchen space such as walls), sink, refrigerator, etc.
- Tableware such as dishes, refrigerators, toilets, baths, toilets, living rooms such as living rooms and bedrooms, textile products such as sofas, cushions, bedding and curtains can be used by contacting them.
- the contact is not particularly limited, and examples include direct application of the composition to the target surface, filling in a spraying device such as a trigger or aerosol, and spraying.
- composition of this invention contact there is no restriction
- it can be liquid, gel, or paste.
- a liquid it can be used as a spray, lotion or the like.
- a known spray container such as a trigger spray container (direct pressure or pressure accumulation type) or a dispenser type pump spray container can be filled, and the spray amount can be adjusted to spray the virus in a place where it is or is thought to exist. And so on.
- the composition of the present invention solubilized on a base material comprising a natural fiber, a regenerated fiber such as rayon, a synthetic fiber such as polyethylene, polypropylene, polyester, or a woven or non-woven web of a mixture of natural fiber and synthetic fiber It can be used by containing a carrier and various additives as required. Specifically, it can be used for sterilization of skin conditioners, pet care products, surfaces of household kitchens and bathrooms, surfaces of exercise equipment, and the like.
- the composition of the present invention can be used by kneading it with a resin.
- resins that can be kneaded include natural, petroleum, synthetic waxes, rosin resins, ethylene-vinyl acetate copolymers, ethylene-vinyl alcohol copolymers, polyesters, polyolefins, acrylic resins, etc. Is mentioned.
- the kneaded material can be used as it is, or can be supported on a porous carrier, formed into a sheet, or used as a laminate.
- porous carrier examples include a natural polymer such as cellulose and chitosan, the above synthetic resin, an inorganic porous material such as calcium silicate, and the like in an arbitrary shape such as a granular shape and a sheet shape.
- the above-mentioned kneaded product or laminate can be used, for example, by installing it in an air conditioner, toilet, bathroom, living room, hospital room, hospital waiting room, dust box, etc. and gradually evaporating the antiviral composition.
- An antiviral composition containing the following components (A) and (B).
- A One or more quaternary ammonium salts selected from dialkyldimethylammonium salts and alkylbenzyldimethylammonium salts 0.05 vol% to 0.5 vol%
- B benzyl alcohol 0.5 vol% to 2 vol% ⁇ 5 >
- A One or more quaternary ammonium salts selected from dialkyldimethylammonium salts and alkylbenzyldimethylammonium salts, and (B) benzyl alcohol is used in combination with the quaternary ammonium salt virus.
- the component (A) is more preferably 0.1 vol% or more, more preferably 0.2 vol% or more, and 0.5% or less, 0.2 vol%. Hereinafter, it is 0.1 vol% or less.
- the component (B) is more preferably 1 vol% or more, more preferably 1.5 vol% or more, and 2 vol% or less, 1.5 vol% or less, or 1 0.0 vol% or less.
- the mass ratio of the components (A) and (B) is preferably (A) / (B) of 3/1 to 1/500, more preferably Is 3/1 to 1/40, more preferably 2/1 to 1/10.
- the quaternary ammonium salt (A) is preferably one or more selected from octylbenzyldimethylammonium chloride, dodecylbenzyldimethylammonium chloride and didecyldimethylammonium chloride. It is. ⁇ 11> In the above ⁇ 1> to ⁇ 9>, the virus to be suitably applied is a non-enveloped virus. ⁇ 12> In the above items ⁇ 1> to ⁇ 9>, a virus that is preferably applied is a virus belonging to the genus Norovirus.
- Example 1 Preparation of antiviral agent
- alkylbenzyldimethylammonium chloride Sanisol C (manufactured by Kao)
- linear alkyl mixture of 12 to 16 carbon atoms
- benzyldimethylammonium chloride and di Decyldimethylammonium chloride (manufactured by Kao)
- BA, (WAKO) benzyl alcohol
- Feline calicivirus F-9 ATCC VR-782 (feline calicivirus (FCV)) was used as the test virus. Since norovirus culture systems have not been established, feline calicivirus classified into the same caliciviridae from morphology and genetic information is used as an alternative virus for norovirus, and a method for confirming virus infectivity is common. (Journal of Hospital Infection, 41, p51-57, 1999). The cells used were CRFK (Crandell Rees feline kidney) cells (Dainippon Sumitomo Pharma Co., Ltd.).
- the medium used was a cell growth medium prepared by adding 10% fetal calf serum to Eagle MEM “Nissui” (1) (Nissui Pharmaceutical).
- Eagle MEM “Nissui” (1) As the cell maintenance medium, Eagle MEM “Nissui” (1) to which 2% fetal calf serum was added was used.
- CRFK cells were monolayer cultured in tissue culture flasks using cell growth media. After monolayer culture, the cell growth medium was removed from the flask and inoculated with the test virus. Next, cell maintenance medium was added and cultured in a carbon dioxide incubator (CO 2 concentration: 5%) at 37 ° C. ⁇ 1 ° C. for 1 to 5 days. After culturing, cell morphology was observed using an inverted phase contrast microscope to confirm that cytopathic effect (CPE) occurred. Next, the culture solution was centrifuged (3,000 rpm, 10 minutes), and the resulting supernatant was used as a virus suspension.
- CO 2 concentration CO 2 concentration: 5%
- Virus inactivation test 0.1 ml of the virus suspension was added to 1 ml of each specimen shown in Tables 1 to 3 and mixed to obtain a working solution. Acting at room temperature, test 1 was diluted with cell maintenance medium after 5, 10, 20 and 30 minutes. Test 2 was similarly diluted after 0.5, 1 and 5 minutes. However, dilution was performed at a dilution concentration confirmed by a preliminary test. In addition, it tested similarly using purified water as a control, and measured the virus infectious titer at the start.
- didecyldimethylammonium chloride alone (0.05%) reduces the infectious value only by 2.4 log TCID 50 in 5 minutes
- didecyldimethylammonium chloride (0.05%) contains 0.5% BA.
- 5% was added, a decrease of 4log TCID 50 was confirmed in 0.5 minutes when 2% BA was added (Table 3). From this, it was shown that the high FCV inactivation effect (norovirus inactivation effect) can be exhibited in a short time by using the cationic surfactant of the present invention and BA together.
- Example 2 (1) Preparation of test solution Alkylbenzyldimethylammonium chloride (Sanisol C (manufactured by Kao), linear alkyl (mixture of 12 to 16 carbon atoms) benzyldimethylammonium chloride) and didecyl as the quaternary ammonium salt of (a) Dimethylammonium chloride (DDAC; manufactured by Kao) was used as benzyl alcohol (BA, (WAKO)) as (b).
- DDAC Dimethylammonium chloride
- BA benzyl alcohol
- Novirus virus-like particles NoV VLPs Shape test method NoV VLPs are expressed and purified in large quantities of capsid proteins that compose norovirus. I'm taking it.
- NoV VLPs were produced using a recombinant protein mass expression system using baculovirus according to the method of Hansman, G. S. et al. (Non-patent Document 1). That is, the gene region encoding the structural protein (accession No.
- SM-2 Bio-beads suspension 50% w / v dispensed in a microtube, stirred for 2 minutes, and then 10 ⁇ L of the supernatant was subjected to TEM observation.
- SM-2 bio beads were suspended in 10 mM HEPES so as to be 50 (w / v)% and autoclaved.
- the NoV VLPs after the contact test were used for TEM (Transmission Electron Microscope) observation, and the anti-norovirus effect of each test solution was predicted by capturing changes in the particle structure.
- FIG. 1 shows a TEM photograph when Sanisole C (0.05%) and BA (2.00%) were added for 0.5 minutes. From FIG. 1, it was confirmed that the particle structure of Norovirus virus like particles (NoV VLPs) composed only of norovirus structural proteins was deformed by the combined action of alkylbenzyldimethylammonium salt and benzyl alcohol. .
- NoV VLPs Norovirus virus like particles
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Abstract
Provided is an anti-virus agent composition which has low levels of irritation and corrosivity and also has an excellent effect of inactivating viruses, particularly an excellent effect of inactivating non-enveloped viruses such as a norovirus.
An anti-virus agent composition comprising the following components (A) and (B): (A) 0.05 to 0.5 vol% inclusive of at least one quaternary ammonium salt selected from a dialkyldimethylammonium salt and an alkylbenzyldimethylammonium salt; and (B) 0.5 to 2 vol% inclusive of benzyl alcohol.
Description
本発明は、ウイルス不活化効果を有する抗ウイルス剤組成物に関する。
The present invention relates to an antiviral composition having a virus inactivating effect.
インフルエンザや風邪等に代表されるウイルス性の感染症は手指や環境の洗浄が重要な予防法の1つと考えられている。その中でも、ウイルス性の急性胃腸炎や下痢症は介護施設や学校、病院等での集団感染として確認されるだけでなく、レストランや調理施設等においても汚染された食品を介した食中毒による集団感染としても数多く報告されている。これらの原因ウイルスとして、非エンベロープウイルスであるノロウイルスやサポウイルス、ロタウイルス等が挙げられ、小児や高齢者への感染は重篤な症状を引き起こすことがある。また、代表的な小児感染症である手足口病や家畜に甚大な被害をもたらす口蹄疫の原因ウイルスも非エンベロープウイルスに分類され、これらの予防法としても手指や環境の衛生対策は非常に重要である。
Viral infectious diseases such as influenza and colds are considered to be one of the important preventive measures to clean fingers and the environment. Among them, viral acute gastroenteritis and diarrhea are not only confirmed as outbreaks in nursing homes, schools, hospitals, etc., but also outbreaks due to food poisoning through contaminated food in restaurants, cooking facilities, etc. There are many reports. These causative viruses include non-enveloped viruses such as norovirus, sapovirus, and rotavirus, and infection of children and the elderly may cause serious symptoms. In addition, hand-foot-and-mouth disease, which is a typical pediatric infection, and foot-and-mouth disease-causing viruses that cause tremendous damage to livestock are also classified as non-enveloped viruses. is there.
特に、ノロウイルスは非細菌性の食中毒および急性胃腸炎の原因ウイルスとして日本国内のみならず、世界中で検出されている。食中毒の原因としては、従来、黄色ブドウ球菌やセレウス菌等の細菌が知られているが、近年、急性胃腸炎を引き起こすノロウイルスによる食中毒が、食中毒発生件数の約25%、患者数では全体の約半分を占め、最も多くなっており、集団感染を引き起こすウイルスとして問題視されている。感染経路は、生カキ等の貝類を食することによる経口感染がよく知られているが、家庭や公共施設等において、汚染食品に触れた人の手指や調理器具上、患者の嘔吐物や糞便中、あるいは患者の周辺環境に存在しているウイルスからの二次感染も数多く報告されている。特にこのような二次感染は、集団感染や感染拡大につながり、患者数の増加の大きな原因となっている。
In particular, norovirus has been detected not only in Japan but around the world as a causative virus for non-bacterial food poisoning and acute gastroenteritis. As a cause of food poisoning, bacteria such as Staphylococcus aureus and Bacillus cereus have been conventionally known. However, in recent years, food poisoning caused by norovirus causing acute gastroenteritis is about 25% of the number of food poisoning cases, and the number of patients is about about the whole. It accounts for half, is the largest, and is regarded as a problem as a virus that causes mass infection. The infection route is well-known for oral infection caused by eating shellfish such as raw oysters. However, at home and public facilities, the patient's vomit and feces on the fingers and cooking utensils of people who touched contaminated food. A number of secondary infections have been reported from viruses present in or around the patient. In particular, such secondary infection leads to mass infection and spread of infection, and is a major cause of increase in the number of patients.
このようなノロウイルスによる食中毒や感染を防止するためには、集団給食施設や飲食店等の大量調理施設や厨房スペース等の床面や壁面、食品加工機器、調理器具等、あるいは家庭における床面や壁面、調理器具、家具類、繊維製品等、さらには公共施設等の床面や壁面、設備、医療機器等などの除ウイルスやウイルスの不活性、および手指の洗浄などの衛生対策を実施することが非常に重要であり、それらの対策は、人や環境を配慮し、且つ簡便に実施されることが望ましい。
In order to prevent such food poisoning and infection caused by norovirus, the floor and walls of mass cooking facilities and kitchen spaces such as collective meal facilities and restaurants, food processing equipment, cooking utensils, etc. Implement hygiene measures such as wall virus, cooking utensils, furniture, textile products, etc., and virus removal and virus inactivation of floors and walls of public facilities, equipment, medical equipment, etc., and hand washing Is very important, and it is desirable that these measures be implemented simply with consideration for people and the environment.
ノロウイルスは、カリシウイルス科、ノロウイルス属に分類されているエンベロープ(膜状構造)を持たないRNAウイルスであり、酸性(胃酸)に対して強い抵抗力を有し、少量(10~100個程度)で感染することが知られている。
現状では、ノロウイルスに対するワクチンや治療薬は存在せず、原因となり得る食品や調理器具、手指の洗浄や消毒等により除ウイルスやウイルス不活性化をすることでノロウイルス感染を予防することが唯一の対処法である。しかしながら、ノロウイルスは、物理化学的抵抗性が強いため、多くの細菌類に対して有効であるエタノールやカチオン界面活性剤を含む消毒剤などもノロウイルスに対しては一般的な使用法において十分な効果を得られない場合がある。そのため、ノロウイルスの不活化には、塩素系漂白剤(次亜塩素酸ナトリウム等)やヨード剤(ポビドンヨード等)、アルデヒド剤(グルタラール等)、過酢酸製剤などの消毒剤が使用されている。しかしながら、斯かる消毒剤は、人に対して刺激が強く、また金属を腐食するという問題がある。また、塩素系漂白剤などでは繊維の色柄などを漂白する作用があり、繊維製品や衣類への使用においては制限が生じる。そのため、使用者の安全や使用する対象物および使用場面を考慮すると、生活環境、手指や調理器具、衣類等にこれらの薬剤を用いることには制限がある。 Norovirus is an RNA virus that does not have an envelope (membrane-like structure) classified in the Caliciviridae and Norovirus genus, has a strong resistance to acid (gastric acid), and a small amount (about 10 to 100). It is known to be infected with.
At present, there are no vaccines or treatments for norovirus, and the only treatment is to prevent norovirus infection by eliminating viruses or inactivating the virus by cleaning or disinfecting food, cooking utensils, and fingers that may cause it. Is the law. However, since norovirus has strong physicochemical resistance, ethanol and disinfectants including cationic surfactants that are effective against many bacteria are effective against norovirus in general usage. You may not get. Therefore, disinfectants such as chlorine bleach (sodium hypochlorite, etc.), iodine agents (povidone iodine, etc.), aldehyde agents (glutaral, etc.) and peracetic acid preparations are used for inactivating norovirus. However, such disinfectants are highly irritating to humans and corrode metals. In addition, chlorine-based bleaching agent has the effect of bleaching the color pattern of the fiber, and there is a limit in use for textile products and clothing. For this reason, in consideration of the safety of the user, the object to be used, and the usage scene, there are limitations on using these drugs in living environments, fingers, cooking utensils, clothing, and the like.
現状では、ノロウイルスに対するワクチンや治療薬は存在せず、原因となり得る食品や調理器具、手指の洗浄や消毒等により除ウイルスやウイルス不活性化をすることでノロウイルス感染を予防することが唯一の対処法である。しかしながら、ノロウイルスは、物理化学的抵抗性が強いため、多くの細菌類に対して有効であるエタノールやカチオン界面活性剤を含む消毒剤などもノロウイルスに対しては一般的な使用法において十分な効果を得られない場合がある。そのため、ノロウイルスの不活化には、塩素系漂白剤(次亜塩素酸ナトリウム等)やヨード剤(ポビドンヨード等)、アルデヒド剤(グルタラール等)、過酢酸製剤などの消毒剤が使用されている。しかしながら、斯かる消毒剤は、人に対して刺激が強く、また金属を腐食するという問題がある。また、塩素系漂白剤などでは繊維の色柄などを漂白する作用があり、繊維製品や衣類への使用においては制限が生じる。そのため、使用者の安全や使用する対象物および使用場面を考慮すると、生活環境、手指や調理器具、衣類等にこれらの薬剤を用いることには制限がある。 Norovirus is an RNA virus that does not have an envelope (membrane-like structure) classified in the Caliciviridae and Norovirus genus, has a strong resistance to acid (gastric acid), and a small amount (about 10 to 100). It is known to be infected with.
At present, there are no vaccines or treatments for norovirus, and the only treatment is to prevent norovirus infection by eliminating viruses or inactivating the virus by cleaning or disinfecting food, cooking utensils, and fingers that may cause it. Is the law. However, since norovirus has strong physicochemical resistance, ethanol and disinfectants including cationic surfactants that are effective against many bacteria are effective against norovirus in general usage. You may not get. Therefore, disinfectants such as chlorine bleach (sodium hypochlorite, etc.), iodine agents (povidone iodine, etc.), aldehyde agents (glutaral, etc.) and peracetic acid preparations are used for inactivating norovirus. However, such disinfectants are highly irritating to humans and corrode metals. In addition, chlorine-based bleaching agent has the effect of bleaching the color pattern of the fiber, and there is a limit in use for textile products and clothing. For this reason, in consideration of the safety of the user, the object to be used, and the usage scene, there are limitations on using these drugs in living environments, fingers, cooking utensils, clothing, and the like.
したがって、近年、刺激性や腐食性が少なく、あるいは繊維製品にも使用できるウイルスを不活化できる手段が求められ、例えば、低級アルコール、アルカリ性物質及びカチオン界面活性剤を含む組成物(特許文献1)、過酸化水素、ベンジルアルコール及び銀成分を含有する組成物(特許文献2)、特定のアミン及び/又は第四級アンモニウム塩と、特定のアルカノールアミン類を含む組成物(特許文献3)、第四級アンモニウム塩を有効成分とし、pHが5~9である組成物(特許文献4)、あるいは天然物タンニンを含有する植物抽出物を有効成分とする組成物(特許文献5)が報告されている。
Therefore, in recent years, means that can inactivate viruses that are less irritating and corrosive, or that can be used in textile products are required. For example, a composition containing a lower alcohol, an alkaline substance and a cationic surfactant (Patent Document 1) , A composition containing hydrogen peroxide, benzyl alcohol and a silver component (Patent Document 2), a composition containing a specific amine and / or a quaternary ammonium salt and a specific alkanolamine (Patent Document 3), A composition having a quaternary ammonium salt as an active ingredient and a pH of 5 to 9 (Patent Document 4) or a composition containing a plant extract containing a natural product tannin as an active ingredient (Patent Document 5) has been reported. Yes.
しかしながら、これらの組成物においても、ウイルスの不活性化効果を発揮するのに時間がかかるために手指の消毒や洗浄作業に用いるには効果が不十分であったり、短時間で効果を発揮することが期待されていてもウイルス感染力価の減少が不十分だったりする等のウイルス不活化効果の点で、未だ充分であるとは云えない。また、アルカリ性である、あるいは特定成分を含むなどその組成上限られた製品処方にのみしか応用できないなどの問題もある。
However, even in these compositions, since it takes time to exert the virus inactivating effect, the effect is insufficient for use in hand disinfection and washing operations, or the effect is exhibited in a short time. However, it is still not sufficient in terms of virus inactivation effects such as insufficient reduction of virus infection titer. In addition, there is a problem that it can be applied only to a product formulation that is alkaline or contains a specific component and has an upper composition limit.
本発明は、以下の1)~5)に係るものである。
1)次の成分(A)及び(B)を含有する抗ウイルス剤組成物。
(A)ジアルキルジメチルアンモニウム塩及びアルキルベンジルジメチルアンモニウム塩から選ばれる1種以上の第4級アンモニウム塩 0.05vol%以上0.5vol%以下
(B)ベンジルアルコール 0.5vol%以上2vol%以下
2)次の成分(A)及び(B)を含有する組成物を用いるウイルス不活化方法。
(A)ジアルキルジメチルアンモニウム塩及びアルキルベンジルジメチルアンモニウム塩から選ばれる1種以上の第4級アンモニウム塩 0.05vol%以上0.5vol%以下
(B)ベンジルアルコール 0.5vol%以上2vol%以下
3)ウイルス不活化のための、次の成分(A)及び(B)を含有する組成物の使用。
(A)ジアルキルジメチルアンモニウム塩及びアルキルベンジルジメチルアンモニウム塩から選ばれる1種以上の第4級アンモニウム塩 0.05vol%以上0.5vol%以下
(B)ベンジルアルコール 0.5vol%以上2vol%以下
4)(A)ジアルキルジメチルアンモニウム塩及びアルキルベンジルジメチルアンモニウム塩から選ばれる1種以上の第4級アンモニウム塩に、(B)ベンジルアルコールを併用することを特徴とする、前記第4級アンモニウム塩のウイルス不活化効果の増強方法。
5)(A)ジアルキルジメチルアンモニウム塩及びアルキルベンジルジメチルアンモニウム塩から選ばれる1種以上の第4級アンモニウム塩のウイルス不活化効果を増強するための、前記(A)の第4級アンモニウム塩と併用する(B)ベンジルアルコールの使用。 The present invention relates to the following 1) to 5).
1) Antiviral composition containing the following components (A) and (B).
(A) One or more quaternary ammonium salts selected from dialkyldimethylammonium salts and alkylbenzyldimethylammonium salts 0.05 vol% to 0.5 vol% (B) benzyl alcohol 0.5 vol% to 2 vol% 2) A virus inactivation method using a composition containing the following components (A) and (B).
(A) One or more quaternary ammonium salts selected from dialkyldimethylammonium salts and alkylbenzyldimethylammonium salts 0.05 vol% to 0.5 vol% (B) benzyl alcohol 0.5 vol% to 2 vol% 3) Use of a composition containing the following components (A) and (B) for virus inactivation:
(A) One or more quaternary ammonium salts selected from dialkyldimethylammonium salts and alkylbenzyldimethylammonium salts 0.05 vol% to 0.5 vol% (B) benzyl alcohol 0.5 vol% to 2 vol% 4) (A) One or more quaternary ammonium salts selected from dialkyldimethylammonium salts and alkylbenzyldimethylammonium salts are used in combination with (B) benzyl alcohol. A method for enhancing the activation effect.
5) (A) Combined with the quaternary ammonium salt of (A) above to enhance the virus inactivating effect of one or more quaternary ammonium salts selected from dialkyldimethylammonium salts and alkylbenzyldimethylammonium salts (B) Use of benzyl alcohol.
1)次の成分(A)及び(B)を含有する抗ウイルス剤組成物。
(A)ジアルキルジメチルアンモニウム塩及びアルキルベンジルジメチルアンモニウム塩から選ばれる1種以上の第4級アンモニウム塩 0.05vol%以上0.5vol%以下
(B)ベンジルアルコール 0.5vol%以上2vol%以下
2)次の成分(A)及び(B)を含有する組成物を用いるウイルス不活化方法。
(A)ジアルキルジメチルアンモニウム塩及びアルキルベンジルジメチルアンモニウム塩から選ばれる1種以上の第4級アンモニウム塩 0.05vol%以上0.5vol%以下
(B)ベンジルアルコール 0.5vol%以上2vol%以下
3)ウイルス不活化のための、次の成分(A)及び(B)を含有する組成物の使用。
(A)ジアルキルジメチルアンモニウム塩及びアルキルベンジルジメチルアンモニウム塩から選ばれる1種以上の第4級アンモニウム塩 0.05vol%以上0.5vol%以下
(B)ベンジルアルコール 0.5vol%以上2vol%以下
4)(A)ジアルキルジメチルアンモニウム塩及びアルキルベンジルジメチルアンモニウム塩から選ばれる1種以上の第4級アンモニウム塩に、(B)ベンジルアルコールを併用することを特徴とする、前記第4級アンモニウム塩のウイルス不活化効果の増強方法。
5)(A)ジアルキルジメチルアンモニウム塩及びアルキルベンジルジメチルアンモニウム塩から選ばれる1種以上の第4級アンモニウム塩のウイルス不活化効果を増強するための、前記(A)の第4級アンモニウム塩と併用する(B)ベンジルアルコールの使用。 The present invention relates to the following 1) to 5).
1) Antiviral composition containing the following components (A) and (B).
(A) One or more quaternary ammonium salts selected from dialkyldimethylammonium salts and alkylbenzyldimethylammonium salts 0.05 vol% to 0.5 vol% (B) benzyl alcohol 0.5 vol% to 2 vol% 2) A virus inactivation method using a composition containing the following components (A) and (B).
(A) One or more quaternary ammonium salts selected from dialkyldimethylammonium salts and alkylbenzyldimethylammonium salts 0.05 vol% to 0.5 vol% (B) benzyl alcohol 0.5 vol% to 2 vol% 3) Use of a composition containing the following components (A) and (B) for virus inactivation:
(A) One or more quaternary ammonium salts selected from dialkyldimethylammonium salts and alkylbenzyldimethylammonium salts 0.05 vol% to 0.5 vol% (B) benzyl alcohol 0.5 vol% to 2 vol% 4) (A) One or more quaternary ammonium salts selected from dialkyldimethylammonium salts and alkylbenzyldimethylammonium salts are used in combination with (B) benzyl alcohol. A method for enhancing the activation effect.
5) (A) Combined with the quaternary ammonium salt of (A) above to enhance the virus inactivating effect of one or more quaternary ammonium salts selected from dialkyldimethylammonium salts and alkylbenzyldimethylammonium salts (B) Use of benzyl alcohol.
本発明は、刺激性、腐食性が少なく、ウイルス不活化効果、特にノロウイルスのような非エンベロープ型ウイルスに対して優れた不活化効果を有する抗ウイルス剤組成物を提供することに関する。
The present invention relates to providing an antiviral composition which has little irritation and corrosivity and has a virus inactivating effect, particularly an excellent inactivating effect against non-enveloped viruses such as Norovirus.
本発明者らは、ノロウイルス等の非エンベロープ型ウイルスの感染防止に有効な成分について検討したところ、特定の第4級アンモニウム塩とベンジルアルコールを組み合わせて用いた場合に、当該第4級アンモニウム塩を単独で用いた場合よりもウイルス不活化効果が大きく上昇し、抗ウイルス剤組成物として有用であることを見出した。
The present inventors have examined components effective for preventing infection of non-enveloped viruses such as Norovirus. When a specific quaternary ammonium salt and benzyl alcohol are used in combination, the quaternary ammonium salt is used. It was found that the virus inactivating effect was greatly increased as compared with the case of using alone, and it was useful as an antiviral composition.
本発明の組成物は、ノロウイルス等の非エンベロープ型ウイルスに対して、優れた抗ウイルス作用を有し、且つ刺激性、腐食性が少ないことから、これを用いることにより、安全に、且つ短時間で、大量調理施設、厨房スペース等の床面や壁面、医療機器、食品加工機器、調理器具等に付着した当該ウイルスを不活化できる。さらに、一般家庭における住居内の床面や壁面、家具等に付着したウイルスの不活性化や手指の消毒に有効に使用できる。
The composition of the present invention has an excellent antiviral action against non-enveloped viruses such as Norovirus, and is less irritating and corrosive, so that it can be used safely and for a short time. Thus, it is possible to inactivate the virus attached to floors and walls of large-scale cooking facilities, kitchen spaces, etc., medical equipment, food processing equipment, cooking utensils and the like. Furthermore, it can be effectively used to inactivate viruses and disinfect hands and fingers attached to floors, walls, furniture, and the like in the dwellings of ordinary households.
成分(A)の第4級アンモニウム塩である、ジアルキルジメチルアンモニウム塩及びアルキルベンジルジメチルアンモニウム塩は、抗菌性のカチオン界面活性剤として公知の化合物である。これらは、単独で用いてもよく、2種以上を混合して用いてもよい。
本発明において、ジアルキルジメチルアンモニウム塩及びアルキルベンジルジメチルアンモニウム塩としては、好ましくは、それぞれ、ジアルキル(C8-18)ジメチルアンモニウム塩、アルキル(C12-16)ベンジルジメチルアンモニウム塩が挙げられる。 Dialkyldimethylammonium salt and alkylbenzyldimethylammonium salt, which are quaternary ammonium salts of component (A), are known compounds as antibacterial cationic surfactants. These may be used alone or in combination of two or more.
In the present invention, the dialkyldimethylammonium salt and the alkylbenzyldimethylammonium salt preferably include a dialkyl (C 8-18 ) dimethylammonium salt and an alkyl (C 12-16 ) benzyldimethylammonium salt, respectively.
本発明において、ジアルキルジメチルアンモニウム塩及びアルキルベンジルジメチルアンモニウム塩としては、好ましくは、それぞれ、ジアルキル(C8-18)ジメチルアンモニウム塩、アルキル(C12-16)ベンジルジメチルアンモニウム塩が挙げられる。 Dialkyldimethylammonium salt and alkylbenzyldimethylammonium salt, which are quaternary ammonium salts of component (A), are known compounds as antibacterial cationic surfactants. These may be used alone or in combination of two or more.
In the present invention, the dialkyldimethylammonium salt and the alkylbenzyldimethylammonium salt preferably include a dialkyl (C 8-18 ) dimethylammonium salt and an alkyl (C 12-16 ) benzyldimethylammonium salt, respectively.
すなわち、ジアルキルジメチルアンモニウム塩におけるアルキル基としては、炭素数8~18のアルキル基、好ましくは炭素数8~18の直鎖アルキル基が挙げられる。具体的には、例えばオクチル、デシル、ドデシル(ラウリル)、テトラデシル(ミリスチル)、ヘキサデシル(セチル)、ヘプタデシル、オクタデシル(ステアリル)が挙げられ、より好ましくはオクチル、デシル、ドデシルである。
That is, the alkyl group in the dialkyldimethylammonium salt includes an alkyl group having 8 to 18 carbon atoms, preferably a linear alkyl group having 8 to 18 carbon atoms. Specific examples include octyl, decyl, dodecyl (lauryl), tetradecyl (myristyl), hexadecyl (cetyl), heptadecyl, octadecyl (stearyl), and more preferably octyl, decyl, and dodecyl.
また、アルキルベンジルジメチルアンモニウム塩におけるアルキル基としては、炭素数12~16のアルキル基、好ましくは炭素数12~16の直鎖アルキル基が挙げられる。具体的には、例えばドデシル(ラウリル)、テトラデシル(ミリスチル)、ヘキサデシル(セチル)が挙げられる。
The alkyl group in the alkylbenzyldimethylammonium salt includes an alkyl group having 12 to 16 carbon atoms, preferably a linear alkyl group having 12 to 16 carbon atoms. Specific examples include dodecyl (lauryl), tetradecyl (myristyl), and hexadecyl (cetyl).
好適なジアルキルジメチルアンモニウム塩としては、ジデシルジメチルアンモニウム塩が挙げられ、アルキルベンジルジメチルアンモニウム塩としては、ドデシルベンジルジメチルアンモニウム塩、テトラデシルベンジルジメチルアンモニウム塩、ヘキサデシルベンジルジメチルアンモニウム塩が挙げられる。
Suitable dialkyldimethylammonium salts include didecyldimethylammonium salts, and alkylbenzyldimethylammonium salts include dodecylbenzyldimethylammonium salts, tetradecylbenzyldimethylammonium salts, and hexadecylbenzyldimethylammonium salts.
アンモニウム塩は、F-、Cl-、Br-、I-等のハロゲン化物イオン、NO3
-、及びSO4
2-等との塩が挙げられるが、ハロゲン化物イオンとの塩が好ましく、塩化物イオンとの塩がより好ましい。
Ammonium salts include salts with halide ions such as F − , Cl − , Br − and I − , NO 3 − , SO 4 2−, etc., and salts with halide ions are preferred and chlorides. More preferred are salts with ions.
より好適な第4級アンモニウム塩として、ドデシルベンジルジメチルアンモニウムクロライド、テトラデシルベンジルジメチルアンモニウムクロライド、ヘキサデシルベンジルジメチルアンモニウムクロライド、ジデシルジメチルアンモニウムクロライドを挙げることができる。
More preferable quaternary ammonium salts include dodecylbenzyldimethylammonium chloride, tetradecylbenzyldimethylammonium chloride, hexadecylbenzyldimethylammonium chloride, and didecyldimethylammonium chloride.
上記本発明の第4級アンモニウム塩は、公知の方法を用いて製造することができ、市販品を用いることも可能である。例えば、ジアルキルジメチルアンモニウム塩としてコータミンD10P(花王(株)製)、アルキルベンジルジメチルアンモニウム塩として、サニゾール08、サニゾールC(花王(株)製)等を購入して用いることができる。
The quaternary ammonium salt of the present invention can be produced by a known method, and a commercially available product can also be used. For example, Cotamin D10P (manufactured by Kao Corporation) as a dialkyldimethylammonium salt and Sanizol 08, Sanisole C (manufactured by Kao Corporation), etc. can be purchased and used as an alkylbenzyldimethylammonium salt.
上記第4級アンモニウム塩は、単独でも60分程度の接触時間では、ノロウイルス(ネコカリシウイルス(FCV)による代替実験による)に対して不活化効果を示すが、短時間ではその効果は不十分であり、長時間あるいは高濃度で用いなければ有意な不活化効果が認められない。
The quaternary ammonium salt alone has an inactivating effect against norovirus (by an alternative experiment with feline calicivirus (FCV)) at a contact time of about 60 minutes alone, but the effect is insufficient in a short time. There is no significant inactivation effect unless used for a long time or at a high concentration.
成分(B)のベンジルアルコールは、市販品を購入して用いることができる。例えば、関東化学(株)や東京化成工業(株)の製品を購入して用いることができる。
尚、抗ウイルス作用に影響を及ぼさない範囲で、ベンジルアルコールと共に、他の有機溶剤を混合して用いることができる。 The component (B) benzyl alcohol can be used by purchasing a commercial product. For example, products from Kanto Chemical Co., Inc. or Tokyo Chemical Industry Co., Ltd. can be purchased and used.
In addition, other organic solvents can be mixed and used with benzyl alcohol as long as the antiviral effect is not affected.
尚、抗ウイルス作用に影響を及ぼさない範囲で、ベンジルアルコールと共に、他の有機溶剤を混合して用いることができる。 The component (B) benzyl alcohol can be used by purchasing a commercial product. For example, products from Kanto Chemical Co., Inc. or Tokyo Chemical Industry Co., Ltd. can be purchased and used.
In addition, other organic solvents can be mixed and used with benzyl alcohol as long as the antiviral effect is not affected.
上記(A)第4級アンモニウム塩及び(B)ベンジルアルコールを含有する本発明の組成物では、第4級アンモニウム塩のノロウイルス(ネコカリシウイルス(FCV)による代替実験による)に対する抗ウイルス活性が格段に向上し、第4級アンモニウム塩を単独で用いた場合には抗菌力を十分に発揮し得ない濃度及び接触時間においても、優れたウイルス不活化効果を発揮する。
In the composition of the present invention containing the above (A) quaternary ammonium salt and (B) benzyl alcohol, the antiviral activity of the quaternary ammonium salt against norovirus (by an alternative experiment with feline calicivirus (FCV)) is remarkably increased. When a quaternary ammonium salt is used alone, an excellent virus inactivating effect is exhibited even at a concentration and contact time at which antibacterial activity cannot be sufficiently exhibited.
本発明の組成物は、ウイルスの感染又は増殖能力を除去又は著しく低下させるウイルス不活化効果を発揮するものであればよく、ウイルス粒子や核酸(RNA)を変性させたり、崩壊させたりするものでも、ウイルスや宿主細胞の表面への吸着やウイルスと酵素との結合等により、結果的にウイルスの感染又は増殖能力を低減又は阻害させることができるものでもよい。
The composition of the present invention may be any composition that exhibits a virus inactivation effect that removes or significantly reduces the ability to infect or proliferate viruses, and may denature or disrupt virus particles and nucleic acids (RNA). As a result, it may be possible to reduce or inhibit the ability of the virus to infect or proliferate by adsorption to the surface of the virus or host cell, binding of the virus with an enzyme, or the like.
ここで、「ウイルス」としては、好適には、非エンベロープ型ウイルス、すなわちエンベロープを持たない一本鎖(+)RNAウイルス、一本鎖(-)RNAウイルス、二本鎖RNAウイルス、一本鎖DNAウイルス、および二本鎖DNAウイルスが挙げられる。斯かるウイルスとしては、カリシウイルス科、ピコルナウイルス科、パルボウイルス科、パピローマウイルス科、ポリオーマウイルス科、アデノウイルス科に属するウイルスが挙げられる。
本発明の組成物は、上記の中でも、カリシウイルス科ウイルス(一本鎖(+)ウイルス)に対する不活化効果に優れており、カリシウイルス科ウイルスの中でも、ベシウイルス属、ノロウイルス属及びサポウイルス属に属するウイルスに対する不活化効果に優れ、特にベシウイルス属とノロウイルス属に属するウイルスに対する不活化効果に優れている。 Here, the “virus” is preferably a non-enveloped virus, that is, a single-stranded (+) RNA virus having no envelope, a single-stranded (−) RNA virus, a double-stranded RNA virus, a single-stranded virus. Examples include DNA viruses and double-stranded DNA viruses. Examples of such viruses include viruses belonging to the Caliciviridae, Picornaviridae, Parvoviridae, Papillomaviridae, Polyomaviridae, and Adenoviridae families.
Among the above, the composition of the present invention is excellent in inactivating effect against Caliciviridae virus (single-stranded (+) virus), and among the Caliciviridae viruses, the genera Besivirus, Norovirus and Sapovirus It has an excellent inactivation effect on viruses belonging to the group, and in particular has an excellent inactivation effect on viruses belonging to the genus Besivirus and Norovirus.
本発明の組成物は、上記の中でも、カリシウイルス科ウイルス(一本鎖(+)ウイルス)に対する不活化効果に優れており、カリシウイルス科ウイルスの中でも、ベシウイルス属、ノロウイルス属及びサポウイルス属に属するウイルスに対する不活化効果に優れ、特にベシウイルス属とノロウイルス属に属するウイルスに対する不活化効果に優れている。 Here, the “virus” is preferably a non-enveloped virus, that is, a single-stranded (+) RNA virus having no envelope, a single-stranded (−) RNA virus, a double-stranded RNA virus, a single-stranded virus. Examples include DNA viruses and double-stranded DNA viruses. Examples of such viruses include viruses belonging to the Caliciviridae, Picornaviridae, Parvoviridae, Papillomaviridae, Polyomaviridae, and Adenoviridae families.
Among the above, the composition of the present invention is excellent in inactivating effect against Caliciviridae virus (single-stranded (+) virus), and among the Caliciviridae viruses, the genera Besivirus, Norovirus and Sapovirus It has an excellent inactivation effect on viruses belonging to the group, and in particular has an excellent inactivation effect on viruses belonging to the genus Besivirus and Norovirus.
本発明の組成物において、成分(A)と(B)の質量比は、(A)/(B)が3/1~1/500、より3/1~1/40、更に2/1~1/10であるのが好ましい。
In the composition of the present invention, the mass ratio of the components (A) and (B) is such that (A) / (B) is 3/1 to 1/500, more preferably 3/1 to 1/40, and further 2/1 to 1/10 is preferable.
本発明の組成物は、成分(A)及び(B)のみで、或いは必要に応じて、抗ウイルス活性の更なる向上や効果の持続性等を図るために、他の成分、例えば、キレート剤、水溶性溶剤、その他の界面活性剤等と共に、大量調理施設、厨房スペース等の床面や壁面、医療機器、食品加工機器、調理器具等の洗浄等に使用される製品や製剤および各種住環境に使用される製品や製剤(例えば、台所用洗剤、蛇口ケア剤、風呂用洗剤、トイレ用洗剤、床や家具の掃除用品等)や衣類や繊維製品に使用される製剤に抗ウイルス活性を付与するための素材として使用することができる。
The composition of the present invention comprises only other components (A) and (B) or, if necessary, other components such as a chelating agent in order to further improve the antiviral activity and maintain the effect. Along with water-soluble solvents, other surfactants, etc., products and preparations used for cleaning of floors and walls of large-scale cooking facilities, kitchen spaces, medical equipment, food processing equipment, cooking utensils, and various living environments Providing antiviral activity to products and preparations used in foods (eg kitchen detergents, faucet care agents, bath detergents, toilet cleaners, floor and furniture cleaning products, etc.) and clothes and textile products Can be used as a material for.
ここで、キレート剤としては(1)トリポリリン酸、ピロリン酸、オルソリン酸、ヘキサメタリン酸及びこれらのアルカリ金属塩、(2)エチレンジアミン四酢酸、ヒドロキシイミノ二酢酸、ジヒドロキシエチルグリシン、ニトリロ三酢酸、ヒドロキシエチレンジアミン三酢酸、ジエチレントリアミン五酢酸、トリエチレンテトラミン六酢酸及びこれらのアルカリ金属塩もしくはアルカリ土類金属塩、(3)アミノトリメチレンホスホン酸、1-ヒドロキシエチリデン-1,1-ジホスホン酸、エチレンジアミンテトラメチレンホスホン酸、ジエチレントリアミンペンタメチレンホスホン酸、アミノトリメチレンホスホン酸のN-オキサイド及びこれらのアルカリ金属塩もしくはアルカリ土類金属塩、(4)アクリル酸及びメタクリル酸から選ばれるモノマーの単一重合体又は共重合体、アクリル酸-マレイン酸共重合体、ポリα-ヒドロキアクリル酸及びそのアルカリ金属塩、(5)クエン酸、コハク酸、リンゴ酸、フマル酸、酒石酸、マロン酸、マレイン酸から選ばれる多価カルボン酸及びそれらのアルカリ金属塩から選ばれる1種以上、(6)アルキルグリシン-N,N-ジ酢酸、アスパラギン酸-N,N-ジ酢酸、セリン-N,N-ジ酢酸、グルタミン酸二酢酸、エチレンジアミンジコハク酸又はこれらの塩等が挙げられる。
Here, as the chelating agent, (1) tripolyphosphoric acid, pyrophosphoric acid, orthophosphoric acid, hexametaphosphoric acid and alkali metal salts thereof, (2) ethylenediaminetetraacetic acid, hydroxyiminodiacetic acid, dihydroxyethylglycine, nitrilotriacetic acid, hydroxyethylenediamine Triacetic acid, diethylenetriaminepentaacetic acid, triethylenetetraminehexaacetic acid and alkali metal salts or alkaline earth metal salts thereof, (3) aminotrimethylenephosphonic acid, 1-hydroxyethylidene-1,1-diphosphonic acid, ethylenediaminetetramethylenephosphone Acid, diethylenetriaminepentamethylenephosphonic acid, N-oxide of aminotrimethylenephosphonic acid and alkali metal salts or alkaline earth metal salts thereof, (4) acrylic acid and methacrylic acid? Monomers or copolymers of selected monomers, acrylic acid-maleic acid copolymer, poly α-hydroxyacrylic acid and alkali metal salts thereof, (5) citric acid, succinic acid, malic acid, fumaric acid, tartaric acid, One or more polyvalent carboxylic acids selected from malonic acid and maleic acid and alkali metal salts thereof; (6) alkylglycine-N, N-diacetic acid, aspartic acid-N, N-diacetic acid, serine- Examples thereof include N, N-diacetic acid, glutamic acid diacetic acid, ethylenediamine disuccinic acid, and salts thereof.
また、本発明の組成物には、さらに、例えば、油分、高級脂肪酸、シリコーン類、pH調整剤、増粘剤、懸濁剤、粉末成分、天然抽出物、色素、香料等の添加剤を適宜配合し、撹拌混合して分散又は溶解させる、抗ウイルス剤組成物を製造するために使用することができる。
In addition, the composition of the present invention may further contain, for example, additives such as oil, higher fatty acids, silicones, pH adjusters, thickeners, suspending agents, powder components, natural extracts, pigments, and fragrances as appropriate. It can be used to produce an antiviral composition that is blended and stirred and dispersed or dissolved.
ここで、pH調整剤としては塩酸や硫酸など無機酸や、クエン酸、コハク酸、リンゴ酸、フマル酸、酒石酸、マロン酸、マレイン酸などの有機酸などの酸剤や、水酸化ナトリウムや水酸化カリウム、アンモニアやその誘導体、モノエタノールアミンやジエタノールアミン、トリエタノールアミンなどのアミン塩など、炭酸ナトリウム、炭酸カリウムなどのアルカリ剤を、単独もしくは複合して用いても構わない。また、これらの酸剤とアルカリ剤を組み合わせて緩衝剤系として用いても構わない。
上記組成物は、上記のpH調整剤により、20℃におけるpHが2~12になるように調整することが好ましく、特にpH4~11になるようにすることがヒトや基材への影響の点から好ましい。 Here, as pH adjusters, acid agents such as inorganic acids such as hydrochloric acid and sulfuric acid, organic acids such as citric acid, succinic acid, malic acid, fumaric acid, tartaric acid, malonic acid, maleic acid, sodium hydroxide and water Alkaline agents such as sodium carbonate and potassium carbonate such as potassium oxide, ammonia and derivatives thereof, amine salts such as monoethanolamine, diethanolamine, and triethanolamine may be used alone or in combination. In addition, these acid agents and alkali agents may be used in combination as a buffer system.
The above composition is preferably adjusted to have a pH of 2 to 12 at 20 ° C. with the above pH adjuster, and particularly to have a pH of 4 to 11 in terms of effects on humans and substrates. To preferred.
上記組成物は、上記のpH調整剤により、20℃におけるpHが2~12になるように調整することが好ましく、特にpH4~11になるようにすることがヒトや基材への影響の点から好ましい。 Here, as pH adjusters, acid agents such as inorganic acids such as hydrochloric acid and sulfuric acid, organic acids such as citric acid, succinic acid, malic acid, fumaric acid, tartaric acid, malonic acid, maleic acid, sodium hydroxide and water Alkaline agents such as sodium carbonate and potassium carbonate such as potassium oxide, ammonia and derivatives thereof, amine salts such as monoethanolamine, diethanolamine, and triethanolamine may be used alone or in combination. In addition, these acid agents and alkali agents may be used in combination as a buffer system.
The above composition is preferably adjusted to have a pH of 2 to 12 at 20 ° C. with the above pH adjuster, and particularly to have a pH of 4 to 11 in terms of effects on humans and substrates. To preferred.
本発明組成物中の成分(A)の第4級アンモニウム塩の含有量は、0.05vol%以上0.5vol%以下であるが、抗ウイルス活性の観点から、より好ましくは0.1vol%以上、更に好ましくは0.2vol%以上であり、製品等への配合の観点から、0.5vol%以下、0.2vol%以下、0.1vol%以下が挙げられる。例えば0.05~0.5vol%、0.1~0.5vol%、0.2~0.5vol%、0.05~0.2vol%、0.05~0.1vol%、0.1~0.2vol%等が挙げられる。
成分(B)のベンジルアルコールの含有量は、0.5~2vol%であるが、抗ウイルス活性の点から、より好ましくは1vol%以上、更に好ましくは1.5vol%以上であり、基材損傷性や配合の観点から2vol%以下、1.5vol%以下、1.0vol%以下が挙げられる。例えば、0.5~2vol%、0.5~1vol%、0.5~1.5vol%、1~2vol%等が挙げられる。 The content of the quaternary ammonium salt of the component (A) in the composition of the present invention is 0.05 vol% or more and 0.5 vol% or less, more preferably 0.1 vol% or more from the viewpoint of antiviral activity. More preferably, it is 0.2 vol% or more, and 0.5 vol% or less, 0.2 vol% or less, or 0.1 vol% or less is mentioned from the viewpoint of blending into a product or the like. For example, 0.05 to 0.5 vol%, 0.1 to 0.5 vol%, 0.2 to 0.5 vol%, 0.05 to 0.2 vol%, 0.05 to 0.1 vol%, 0.1 to 0.2 vol% etc. are mentioned.
The content of benzyl alcohol as component (B) is 0.5 to 2 vol%, but from the viewpoint of antiviral activity, it is more preferably 1 vol% or more, and even more preferably 1.5 vol% or more. From the viewpoint of property and blending, 2 vol% or less, 1.5 vol% or less, or 1.0 vol% or less can be mentioned. Examples thereof include 0.5 to 2 vol%, 0.5 to 1 vol%, 0.5 to 1.5 vol%, and 1 to 2 vol%.
成分(B)のベンジルアルコールの含有量は、0.5~2vol%であるが、抗ウイルス活性の点から、より好ましくは1vol%以上、更に好ましくは1.5vol%以上であり、基材損傷性や配合の観点から2vol%以下、1.5vol%以下、1.0vol%以下が挙げられる。例えば、0.5~2vol%、0.5~1vol%、0.5~1.5vol%、1~2vol%等が挙げられる。 The content of the quaternary ammonium salt of the component (A) in the composition of the present invention is 0.05 vol% or more and 0.5 vol% or less, more preferably 0.1 vol% or more from the viewpoint of antiviral activity. More preferably, it is 0.2 vol% or more, and 0.5 vol% or less, 0.2 vol% or less, or 0.1 vol% or less is mentioned from the viewpoint of blending into a product or the like. For example, 0.05 to 0.5 vol%, 0.1 to 0.5 vol%, 0.2 to 0.5 vol%, 0.05 to 0.2 vol%, 0.05 to 0.1 vol%, 0.1 to 0.2 vol% etc. are mentioned.
The content of benzyl alcohol as component (B) is 0.5 to 2 vol%, but from the viewpoint of antiviral activity, it is more preferably 1 vol% or more, and even more preferably 1.5 vol% or more. From the viewpoint of property and blending, 2 vol% or less, 1.5 vol% or less, or 1.0 vol% or less can be mentioned. Examples thereof include 0.5 to 2 vol%, 0.5 to 1 vol%, 0.5 to 1.5 vol%, and 1 to 2 vol%.
本発明の組成物は、ウイルスの付着のおそれがある箇所、例えば、台所(厨房の床、壁等の厨房スペース等)、流し台、冷蔵庫等の食品を取り扱う場所、包丁、鍋等の調理器具、皿等の食器類、冷蔵庫、トイレ、バス、洗面所、居室、寝室等の居住空間、ソファー、クッション、寝具、カーテン等の繊維製品等に対して、これらに接触させることにより用いることができる。ここで、接触は、特に限定するものではなく、組成物を対象面へ直接かけること、トリガーやエアゾール等の噴霧装置に充填し噴霧することなどが挙げられる。
The composition of the present invention is a place where there is a risk of virus attachment, for example, kitchen (kitchen floor, kitchen space such as walls), sink, refrigerator, etc. Tableware such as dishes, refrigerators, toilets, baths, toilets, living rooms such as living rooms and bedrooms, textile products such as sofas, cushions, bedding and curtains can be used by contacting them. Here, the contact is not particularly limited, and examples include direct application of the composition to the target surface, filling in a spraying device such as a trigger or aerosol, and spraying.
本発明の組成物を接触させるに際しての使用形態に特に制限はない。例えば、液状、ゲル状、又はペースト状とすることができる。
液状の場合には、特にスプレー、ローション等として用いることができる。例えば、トリガースプレー容器(直圧又は蓄圧型)やディスペンサータイプのポンプスプレー容器等の公知のスプレー容器に充填し、噴霧量を調整して、ウイルスが存在する、又は存在すると考えられる場所に噴霧できるようにしたもの等が挙げられる。 There is no restriction | limiting in particular in the usage form at the time of making the composition of this invention contact. For example, it can be liquid, gel, or paste.
In the case of a liquid, it can be used as a spray, lotion or the like. For example, a known spray container such as a trigger spray container (direct pressure or pressure accumulation type) or a dispenser type pump spray container can be filled, and the spray amount can be adjusted to spray the virus in a place where it is or is thought to exist. And so on.
液状の場合には、特にスプレー、ローション等として用いることができる。例えば、トリガースプレー容器(直圧又は蓄圧型)やディスペンサータイプのポンプスプレー容器等の公知のスプレー容器に充填し、噴霧量を調整して、ウイルスが存在する、又は存在すると考えられる場所に噴霧できるようにしたもの等が挙げられる。 There is no restriction | limiting in particular in the usage form at the time of making the composition of this invention contact. For example, it can be liquid, gel, or paste.
In the case of a liquid, it can be used as a spray, lotion or the like. For example, a known spray container such as a trigger spray container (direct pressure or pressure accumulation type) or a dispenser type pump spray container can be filled, and the spray amount can be adjusted to spray the virus in a place where it is or is thought to exist. And so on.
また、ウェット拭取り用品(ぬれナプキン等)として使用することもできる。例えば、天然繊維、レーヨン等の再生繊維、ポリエチレン、ポリプロピレン、ポリエステル等の合成繊維、又は天然繊維と合成繊維との混合物の織布又は不織布ウェブを含む基材に、本発明の組成物、可溶化キャリア、及び必要に応じて各種添加剤を含ませて使用することができる。具体的には、皮膚コンディショナーや、ペットの手入れ用品、家庭の台所やバスルーム等の表面、運動器具等の表面の殺菌等に使用することができる。
Also, it can be used as a wet wipe (such as a wet napkin). For example, the composition of the present invention, solubilized on a base material comprising a natural fiber, a regenerated fiber such as rayon, a synthetic fiber such as polyethylene, polypropylene, polyester, or a woven or non-woven web of a mixture of natural fiber and synthetic fiber It can be used by containing a carrier and various additives as required. Specifically, it can be used for sterilization of skin conditioners, pet care products, surfaces of household kitchens and bathrooms, surfaces of exercise equipment, and the like.
水溶性ゲルや油性ゲルを用いてゲル状にしたり、ペースト状とした場合には、医療用品として、人体、ペット等に直接塗布して使用したり、紙や不織布等に担持させたものを、空気清浄器のフィルターとして用いることもできる。
When it is made into a gel using a water-soluble gel or oil-based gel, or in a paste form, it is used as a medical product by directly applying it to the human body, pets, etc., or carrying it on paper or non-woven fabric, It can also be used as a filter for an air purifier.
さらに、本発明の組成物を樹脂に混練して使用することもできる。混練しうる樹脂としては、天然系、石油系、合成系のワックス、ロジン系樹脂、エチレン-酢酸ビニル共重合体、エチレン-ビニルアルコール共重合体、ポリエステル、ポリオレフィン、アクリル系樹脂等の合成樹脂等が挙げられる。
上記の混練物は、そのまま用いることもできるし、多孔質担体に担持させたり、シート状にしたり、該シート状物を積層体にして用いることもできる。多孔質担体としては、例えば、セルロース、キトサン等の天然高分子、上記の合成樹脂、ケイ酸カルシウム等の無機多孔性物質等を、粒状、シート状等の任意の形状にしたものが挙げられる。上記の混練物や積層体は、例えば、空調設備、トイレ、浴室、居間、病室、病院の待合室、ダストボックス等に設置して、抗ウイルス剤組成物を徐々に揮散させながら利用することもできる。 Furthermore, the composition of the present invention can be used by kneading it with a resin. Examples of resins that can be kneaded include natural, petroleum, synthetic waxes, rosin resins, ethylene-vinyl acetate copolymers, ethylene-vinyl alcohol copolymers, polyesters, polyolefins, acrylic resins, etc. Is mentioned.
The kneaded material can be used as it is, or can be supported on a porous carrier, formed into a sheet, or used as a laminate. Examples of the porous carrier include a natural polymer such as cellulose and chitosan, the above synthetic resin, an inorganic porous material such as calcium silicate, and the like in an arbitrary shape such as a granular shape and a sheet shape. The above-mentioned kneaded product or laminate can be used, for example, by installing it in an air conditioner, toilet, bathroom, living room, hospital room, hospital waiting room, dust box, etc. and gradually evaporating the antiviral composition.
上記の混練物は、そのまま用いることもできるし、多孔質担体に担持させたり、シート状にしたり、該シート状物を積層体にして用いることもできる。多孔質担体としては、例えば、セルロース、キトサン等の天然高分子、上記の合成樹脂、ケイ酸カルシウム等の無機多孔性物質等を、粒状、シート状等の任意の形状にしたものが挙げられる。上記の混練物や積層体は、例えば、空調設備、トイレ、浴室、居間、病室、病院の待合室、ダストボックス等に設置して、抗ウイルス剤組成物を徐々に揮散させながら利用することもできる。 Furthermore, the composition of the present invention can be used by kneading it with a resin. Examples of resins that can be kneaded include natural, petroleum, synthetic waxes, rosin resins, ethylene-vinyl acetate copolymers, ethylene-vinyl alcohol copolymers, polyesters, polyolefins, acrylic resins, etc. Is mentioned.
The kneaded material can be used as it is, or can be supported on a porous carrier, formed into a sheet, or used as a laminate. Examples of the porous carrier include a natural polymer such as cellulose and chitosan, the above synthetic resin, an inorganic porous material such as calcium silicate, and the like in an arbitrary shape such as a granular shape and a sheet shape. The above-mentioned kneaded product or laminate can be used, for example, by installing it in an air conditioner, toilet, bathroom, living room, hospital room, hospital waiting room, dust box, etc. and gradually evaporating the antiviral composition.
上述した実施形態に関し、本発明においては以下の態様が開示される。
<1>次の成分(A)及び(B)を含有する抗ウイルス剤組成物。
(A)ジアルキルジメチルアンモニウム塩及びアルキルベンジルジメチルアンモニウム塩から選ばれる1種以上の第4級アンモニウム塩 0.05vol%以上0.5vol%以下
(B)ベンジルアルコール 0.5vol%以上2vol%以下
<2>次の成分(A)及び(B)を含有する組成物を用いるウイルス不活化方法。
(A)ジアルキルジメチルアンモニウム塩及びアルキルベンジルジメチルアンモニウム塩から選ばれる1種以上の第4級アンモニウム塩 0.05vol%以上0.5vol%以下
(B)ベンジルアルコール 0.5vol%以上2vol%以下
<3>ウイルスの付着のおそれがある箇所に前記組成物を接触させる<2>の方法。
<4>ウイルス不活化のための、次の成分(A)及び(B)を含有する組成物の使用。
(A)ジアルキルジメチルアンモニウム塩及びアルキルベンジルジメチルアンモニウム塩から選ばれる1種以上の第4級アンモニウム塩 0.05vol%以上0.5vol%以下
(B)ベンジルアルコール 0.5vol%以上2vol%以下
<5>(A)ジアルキルジメチルアンモニウム塩及びアルキルベンジルジメチルアンモニウム塩から選ばれる1種以上の第4級アンモニウム塩に、(B)ベンジルアルコールを併用することを特徴とする、前記第4級アンモニウム塩のウイルス不活化効果の増強方法。
<6>(A)ジアルキルジメチルアンモニウム塩及びアルキルベンジルジメチルアンモニウム塩から選ばれる1種以上の第4級アンモニウム塩のウイルス不活化効果を増強するための、前記(A)の第4級アンモニウム塩と併用する(B)ベンジルアルコールの使用。
<7>上記<1>~<6>において、成分(A)は、より好ましくは0.1vol%以上、より好ましくは0.2vol%以上であり、そして0.5%以下、0.2vol%以下、0.1vol%以下である。
<8>上記<1>~<6>において、成分(B)は、より好ましくは1vol%以上、より好ましくは1.5vol%以上であり、そして2vol%以下、1.5vol%以下、又は1.0vol%以下である。
<9>上記<1>~<6>において、成分(A)と(B)の質量比は、好適には(A)/(B)が3/1~1/500であり、より好適には3/1~1/40であり、更に好適には2/1~1/10である。
<10>上記<1>~<9>において、(A)の第4級アンモニウム塩は、好適にはオクチルベンジルジメチルアンモニウムクロライド、ドデシルベンジルジメチルアンモニウムクロライド及びジデシルジメチルアンモニウムクロライドから選ばれる1種以上である。
<11>上記<1>~<9>において、好適に適用されるウイルスは非エンベロープ型ウイルスである。
<12>上記<1>~<9>において、好適に適用されるウイルスはノロウイルス属に属するウイルスである。 With respect to the above-described embodiment, the following aspects are disclosed in the present invention.
<1> An antiviral composition containing the following components (A) and (B).
(A) One or more quaternary ammonium salts selected from dialkyldimethylammonium salts and alkylbenzyldimethylammonium salts 0.05 vol% to 0.5 vol% (B) benzyl alcohol 0.5 vol% to 2 vol% <2 > A virus inactivation method using a composition containing the following components (A) and (B).
(A) One or more quaternary ammonium salts selected from dialkyldimethylammonium salts and alkylbenzyldimethylammonium salts 0.05 vol% to 0.5 vol% (B) benzyl alcohol 0.5 vol% to 2 vol% <3 > The method of <2>, wherein the composition is brought into contact with a place where there is a risk of virus attachment.
<4> Use of a composition containing the following components (A) and (B) for virus inactivation.
(A) One or more quaternary ammonium salts selected from dialkyldimethylammonium salts and alkylbenzyldimethylammonium salts 0.05 vol% to 0.5 vol% (B) benzyl alcohol 0.5 vol% to 2 vol% <5 > (A) One or more quaternary ammonium salts selected from dialkyldimethylammonium salts and alkylbenzyldimethylammonium salts, and (B) benzyl alcohol is used in combination with the quaternary ammonium salt virus. A method for enhancing the inactivation effect.
<6> (A) the quaternary ammonium salt of (A) above for enhancing the virus inactivating effect of one or more quaternary ammonium salts selected from dialkyldimethylammonium salts and alkylbenzyldimethylammonium salts; (B) Use of benzyl alcohol in combination.
<7> In the above items <1> to <6>, the component (A) is more preferably 0.1 vol% or more, more preferably 0.2 vol% or more, and 0.5% or less, 0.2 vol%. Hereinafter, it is 0.1 vol% or less.
<8> In the above items <1> to <6>, the component (B) is more preferably 1 vol% or more, more preferably 1.5 vol% or more, and 2 vol% or less, 1.5 vol% or less, or 1 0.0 vol% or less.
<9> In the above <1> to <6>, the mass ratio of the components (A) and (B) is preferably (A) / (B) of 3/1 to 1/500, more preferably Is 3/1 to 1/40, more preferably 2/1 to 1/10.
<10> In the above items <1> to <9>, the quaternary ammonium salt (A) is preferably one or more selected from octylbenzyldimethylammonium chloride, dodecylbenzyldimethylammonium chloride and didecyldimethylammonium chloride. It is.
<11> In the above <1> to <9>, the virus to be suitably applied is a non-enveloped virus.
<12> In the above items <1> to <9>, a virus that is preferably applied is a virus belonging to the genus Norovirus.
<1>次の成分(A)及び(B)を含有する抗ウイルス剤組成物。
(A)ジアルキルジメチルアンモニウム塩及びアルキルベンジルジメチルアンモニウム塩から選ばれる1種以上の第4級アンモニウム塩 0.05vol%以上0.5vol%以下
(B)ベンジルアルコール 0.5vol%以上2vol%以下
<2>次の成分(A)及び(B)を含有する組成物を用いるウイルス不活化方法。
(A)ジアルキルジメチルアンモニウム塩及びアルキルベンジルジメチルアンモニウム塩から選ばれる1種以上の第4級アンモニウム塩 0.05vol%以上0.5vol%以下
(B)ベンジルアルコール 0.5vol%以上2vol%以下
<3>ウイルスの付着のおそれがある箇所に前記組成物を接触させる<2>の方法。
<4>ウイルス不活化のための、次の成分(A)及び(B)を含有する組成物の使用。
(A)ジアルキルジメチルアンモニウム塩及びアルキルベンジルジメチルアンモニウム塩から選ばれる1種以上の第4級アンモニウム塩 0.05vol%以上0.5vol%以下
(B)ベンジルアルコール 0.5vol%以上2vol%以下
<5>(A)ジアルキルジメチルアンモニウム塩及びアルキルベンジルジメチルアンモニウム塩から選ばれる1種以上の第4級アンモニウム塩に、(B)ベンジルアルコールを併用することを特徴とする、前記第4級アンモニウム塩のウイルス不活化効果の増強方法。
<6>(A)ジアルキルジメチルアンモニウム塩及びアルキルベンジルジメチルアンモニウム塩から選ばれる1種以上の第4級アンモニウム塩のウイルス不活化効果を増強するための、前記(A)の第4級アンモニウム塩と併用する(B)ベンジルアルコールの使用。
<7>上記<1>~<6>において、成分(A)は、より好ましくは0.1vol%以上、より好ましくは0.2vol%以上であり、そして0.5%以下、0.2vol%以下、0.1vol%以下である。
<8>上記<1>~<6>において、成分(B)は、より好ましくは1vol%以上、より好ましくは1.5vol%以上であり、そして2vol%以下、1.5vol%以下、又は1.0vol%以下である。
<9>上記<1>~<6>において、成分(A)と(B)の質量比は、好適には(A)/(B)が3/1~1/500であり、より好適には3/1~1/40であり、更に好適には2/1~1/10である。
<10>上記<1>~<9>において、(A)の第4級アンモニウム塩は、好適にはオクチルベンジルジメチルアンモニウムクロライド、ドデシルベンジルジメチルアンモニウムクロライド及びジデシルジメチルアンモニウムクロライドから選ばれる1種以上である。
<11>上記<1>~<9>において、好適に適用されるウイルスは非エンベロープ型ウイルスである。
<12>上記<1>~<9>において、好適に適用されるウイルスはノロウイルス属に属するウイルスである。 With respect to the above-described embodiment, the following aspects are disclosed in the present invention.
<1> An antiviral composition containing the following components (A) and (B).
(A) One or more quaternary ammonium salts selected from dialkyldimethylammonium salts and alkylbenzyldimethylammonium salts 0.05 vol% to 0.5 vol% (B) benzyl alcohol 0.5 vol% to 2 vol% <2 > A virus inactivation method using a composition containing the following components (A) and (B).
(A) One or more quaternary ammonium salts selected from dialkyldimethylammonium salts and alkylbenzyldimethylammonium salts 0.05 vol% to 0.5 vol% (B) benzyl alcohol 0.5 vol% to 2 vol% <3 > The method of <2>, wherein the composition is brought into contact with a place where there is a risk of virus attachment.
<4> Use of a composition containing the following components (A) and (B) for virus inactivation.
(A) One or more quaternary ammonium salts selected from dialkyldimethylammonium salts and alkylbenzyldimethylammonium salts 0.05 vol% to 0.5 vol% (B) benzyl alcohol 0.5 vol% to 2 vol% <5 > (A) One or more quaternary ammonium salts selected from dialkyldimethylammonium salts and alkylbenzyldimethylammonium salts, and (B) benzyl alcohol is used in combination with the quaternary ammonium salt virus. A method for enhancing the inactivation effect.
<6> (A) the quaternary ammonium salt of (A) above for enhancing the virus inactivating effect of one or more quaternary ammonium salts selected from dialkyldimethylammonium salts and alkylbenzyldimethylammonium salts; (B) Use of benzyl alcohol in combination.
<7> In the above items <1> to <6>, the component (A) is more preferably 0.1 vol% or more, more preferably 0.2 vol% or more, and 0.5% or less, 0.2 vol%. Hereinafter, it is 0.1 vol% or less.
<8> In the above items <1> to <6>, the component (B) is more preferably 1 vol% or more, more preferably 1.5 vol% or more, and 2 vol% or less, 1.5 vol% or less, or 1 0.0 vol% or less.
<9> In the above <1> to <6>, the mass ratio of the components (A) and (B) is preferably (A) / (B) of 3/1 to 1/500, more preferably Is 3/1 to 1/40, more preferably 2/1 to 1/10.
<10> In the above items <1> to <9>, the quaternary ammonium salt (A) is preferably one or more selected from octylbenzyldimethylammonium chloride, dodecylbenzyldimethylammonium chloride and didecyldimethylammonium chloride. It is.
<11> In the above <1> to <9>, the virus to be suitably applied is a non-enveloped virus.
<12> In the above items <1> to <9>, a virus that is preferably applied is a virus belonging to the genus Norovirus.
以下、実施例に基づき本発明をさらに詳細に説明する。
実施例1
(1)抗ウイルス剤の調製
(a)の第4級アンモニウム塩としてアルキルベンジルジメチルアンモニウムクロライド(サニゾールC(花王製)、直鎖アルキル(炭素数12~16の混合物)ベンジルジメチルアンモニウムクロライド)およびジデシルジメチルアンモニウムクロライド(花王製)を、(b)としてベンジルアルコール(BA、(WAKO))を用い、滅菌水にて希釈して、下記表1~表3に示した濃度になるように調製した。 Hereinafter, the present invention will be described in more detail based on examples.
Example 1
(1) Preparation of antiviral agent As the quaternary ammonium salt of (a), alkylbenzyldimethylammonium chloride (Sanisol C (manufactured by Kao), linear alkyl (mixture of 12 to 16 carbon atoms) benzyldimethylammonium chloride) and di Decyldimethylammonium chloride (manufactured by Kao) was prepared using benzyl alcohol (BA, (WAKO)) as (b) and diluted with sterilized water to the concentrations shown in Tables 1 to 3 below. .
実施例1
(1)抗ウイルス剤の調製
(a)の第4級アンモニウム塩としてアルキルベンジルジメチルアンモニウムクロライド(サニゾールC(花王製)、直鎖アルキル(炭素数12~16の混合物)ベンジルジメチルアンモニウムクロライド)およびジデシルジメチルアンモニウムクロライド(花王製)を、(b)としてベンジルアルコール(BA、(WAKO))を用い、滅菌水にて希釈して、下記表1~表3に示した濃度になるように調製した。 Hereinafter, the present invention will be described in more detail based on examples.
Example 1
(1) Preparation of antiviral agent As the quaternary ammonium salt of (a), alkylbenzyldimethylammonium chloride (Sanisol C (manufactured by Kao), linear alkyl (mixture of 12 to 16 carbon atoms) benzyldimethylammonium chloride) and di Decyldimethylammonium chloride (manufactured by Kao) was prepared using benzyl alcohol (BA, (WAKO)) as (b) and diluted with sterilized water to the concentrations shown in Tables 1 to 3 below. .
(2)試験ウイルス及びウイルス浮遊液の調製
試験ウイルスは、Feline calicivirus F-9 ATCC VR-782(ネコカリシウイルス(FCV))を用いた。ノロウイルスは培養系が確立されていないため、ノロウイルスの代替ウイルスとして、形態および遺伝子情報から同じカリシウイルス科に分類されているネコカリシウイルスが用いられており、ウイルス感染力を確認する方法が一般的に採用されている(Journal of Hospital Infection, 41, p51-57, 1999)。
使用細胞はCRFK (Crandell Rees feline kidney) 細胞(大日本住友製薬)を用いた。使用培地は細胞増殖培地としてイーグルMEM「ニッスイ」(1)(日水製薬)に10%牛胎仔血清を添加したものを用いた。細胞維持培地としてイーグルMEM「ニッスイ」(1)に2%牛胎仔血清を添加したものを用いた。 (2) Preparation of test virus and virus suspension Feline calicivirus F-9 ATCC VR-782 (feline calicivirus (FCV)) was used as the test virus. Since norovirus culture systems have not been established, feline calicivirus classified into the same caliciviridae from morphology and genetic information is used as an alternative virus for norovirus, and a method for confirming virus infectivity is common. (Journal of Hospital Infection, 41, p51-57, 1999).
The cells used were CRFK (Crandell Rees feline kidney) cells (Dainippon Sumitomo Pharma Co., Ltd.). The medium used was a cell growth medium prepared by adding 10% fetal calf serum to Eagle MEM “Nissui” (1) (Nissui Pharmaceutical). As the cell maintenance medium, Eagle MEM “Nissui” (1) to which 2% fetal calf serum was added was used.
試験ウイルスは、Feline calicivirus F-9 ATCC VR-782(ネコカリシウイルス(FCV))を用いた。ノロウイルスは培養系が確立されていないため、ノロウイルスの代替ウイルスとして、形態および遺伝子情報から同じカリシウイルス科に分類されているネコカリシウイルスが用いられており、ウイルス感染力を確認する方法が一般的に採用されている(Journal of Hospital Infection, 41, p51-57, 1999)。
使用細胞はCRFK (Crandell Rees feline kidney) 細胞(大日本住友製薬)を用いた。使用培地は細胞増殖培地としてイーグルMEM「ニッスイ」(1)(日水製薬)に10%牛胎仔血清を添加したものを用いた。細胞維持培地としてイーグルMEM「ニッスイ」(1)に2%牛胎仔血清を添加したものを用いた。 (2) Preparation of test virus and virus suspension Feline calicivirus F-9 ATCC VR-782 (feline calicivirus (FCV)) was used as the test virus. Since norovirus culture systems have not been established, feline calicivirus classified into the same caliciviridae from morphology and genetic information is used as an alternative virus for norovirus, and a method for confirming virus infectivity is common. (Journal of Hospital Infection, 41, p51-57, 1999).
The cells used were CRFK (Crandell Rees feline kidney) cells (Dainippon Sumitomo Pharma Co., Ltd.). The medium used was a cell growth medium prepared by adding 10% fetal calf serum to Eagle MEM “Nissui” (1) (Nissui Pharmaceutical). As the cell maintenance medium, Eagle MEM “Nissui” (1) to which 2% fetal calf serum was added was used.
細胞増殖培地を用い、CRFK細胞を組織培養用フラスコ内に単層培養した。単層培養後にフラスコ内から細胞増殖培地を除き、試験ウイルスを接種した。次に、細胞維持培地を加えて37℃±1℃の炭酸ガスインキュベーター(CO2濃度:5%)内で1~5日間培養した。培養後、倒立位相差顕微鏡を用いて細胞の形態を観察し、細胞変性効果(cytopathic effect; CPE)が起こっていることを確認した。次に、培養液を遠心分離(3,000rpm,10分間)し、得られた上澄み液をウイルス浮遊液とした。
CRFK cells were monolayer cultured in tissue culture flasks using cell growth media. After monolayer culture, the cell growth medium was removed from the flask and inoculated with the test virus. Next, cell maintenance medium was added and cultured in a carbon dioxide incubator (CO 2 concentration: 5%) at 37 ° C. ± 1 ° C. for 1 to 5 days. After culturing, cell morphology was observed using an inverted phase contrast microscope to confirm that cytopathic effect (CPE) occurred. Next, the culture solution was centrifuged (3,000 rpm, 10 minutes), and the resulting supernatant was used as a virus suspension.
(3)ウイルス不活化試験
表1~表3に記載したそれぞれの検体1mlにウイルス浮遊液0.1mlを添加、混合し、作用液とした。室温で作用させ、試験1は5,10,20及び30分後に細胞維持培地を用いて希釈した。また、試験2は0.5,1及び5分後に同様に希釈した。ただし、希釈は予備試験により確認した希釈濃度で行った。なお、対照として精製水を用いて同様に試験し、開始時にウイルス感染力価の測定を行った。 (3) Virus inactivation test 0.1 ml of the virus suspension was added to 1 ml of each specimen shown in Tables 1 to 3 and mixed to obtain a working solution. Acting at room temperature, test 1 was diluted with cell maintenance medium after 5, 10, 20 and 30 minutes. Test 2 was similarly diluted after 0.5, 1 and 5 minutes. However, dilution was performed at a dilution concentration confirmed by a preliminary test. In addition, it tested similarly using purified water as a control, and measured the virus infectious titer at the start.
表1~表3に記載したそれぞれの検体1mlにウイルス浮遊液0.1mlを添加、混合し、作用液とした。室温で作用させ、試験1は5,10,20及び30分後に細胞維持培地を用いて希釈した。また、試験2は0.5,1及び5分後に同様に希釈した。ただし、希釈は予備試験により確認した希釈濃度で行った。なお、対照として精製水を用いて同様に試験し、開始時にウイルス感染力価の測定を行った。 (3) Virus inactivation test 0.1 ml of the virus suspension was added to 1 ml of each specimen shown in Tables 1 to 3 and mixed to obtain a working solution. Acting at room temperature, test 1 was diluted with cell maintenance medium after 5, 10, 20 and 30 minutes. Test 2 was similarly diluted after 0.5, 1 and 5 minutes. However, dilution was performed at a dilution concentration confirmed by a preliminary test. In addition, it tested similarly using purified water as a control, and measured the virus infectious titer at the start.
(4)ウイルス感染力価の測定方法
細胞増殖培地を用い、使用細胞を組織培養用マイクロプレート(96well)内で単層培養した後、細胞増殖培地を除き細胞維持培地を0.1mlずつ加えた。次に、作用液を細胞維持培地を用いて10倍段階希釈した。各作用液の希釈液0.1mlを4wellずつに接種し、37℃±1℃の炭酸ガスインキュベーター(CO2濃度:5%)内で4~7日間培養した。培養後、倒立位相差顕微鏡を用いてCPEの有無を観察し、Reed-Muench法(The American journal of hygiene, 27, 493-497, 1938)により50%組織培養感染量(Tissue Culture Infectious Dose; TCID50)を算出して作用液1ml当たりのウイルス感染価に換算した。 (4) Method of measuring virus infection titer Using cell growth medium, the cells used were cultured in a monolayer in a tissue culture microplate (96 well), and then the cell growth medium was removed and 0.1 ml of cell maintenance medium was added. . Next, the working fluid was diluted 10-fold using a cell maintenance medium. 0.1 ml of each working solution was inoculated into 4 wells and cultured in a carbon dioxide incubator (CO 2 concentration: 5%) at 37 ° C. ± 1 ° C. for 4-7 days. After culturing, the presence or absence of CPE was observed using an inverted phase contrast microscope, and 50% tissue culture infectious dose (TCID50) was obtained by the Reed-Muench method (The American journal of hygiene, 27, 493-497, 1938). ) Was calculated and converted to the virus infectivity per ml of working fluid.
細胞増殖培地を用い、使用細胞を組織培養用マイクロプレート(96well)内で単層培養した後、細胞増殖培地を除き細胞維持培地を0.1mlずつ加えた。次に、作用液を細胞維持培地を用いて10倍段階希釈した。各作用液の希釈液0.1mlを4wellずつに接種し、37℃±1℃の炭酸ガスインキュベーター(CO2濃度:5%)内で4~7日間培養した。培養後、倒立位相差顕微鏡を用いてCPEの有無を観察し、Reed-Muench法(The American journal of hygiene, 27, 493-497, 1938)により50%組織培養感染量(Tissue Culture Infectious Dose; TCID50)を算出して作用液1ml当たりのウイルス感染価に換算した。 (4) Method of measuring virus infection titer Using cell growth medium, the cells used were cultured in a monolayer in a tissue culture microplate (96 well), and then the cell growth medium was removed and 0.1 ml of cell maintenance medium was added. . Next, the working fluid was diluted 10-fold using a cell maintenance medium. 0.1 ml of each working solution was inoculated into 4 wells and cultured in a carbon dioxide incubator (CO 2 concentration: 5%) at 37 ° C. ± 1 ° C. for 4-7 days. After culturing, the presence or absence of CPE was observed using an inverted phase contrast microscope, and 50% tissue culture infectious dose (TCID50) was obtained by the Reed-Muench method (The American journal of hygiene, 27, 493-497, 1938). ) Was calculated and converted to the virus infectivity per ml of working fluid.
(5)試験結果
BA単独では、5分間の接触でFCVの感染力価を減少させないことを確認した(表1)。アルキルベンジルジメチルアンモニウムクロライド単独(0.05%)では、FCVの5分間の接触で感染価を2.2logTCID50しか減少しないのに対し、アルキルベンジルジメチルアンモニウムクロライド(0.05%)に1.0%および2.0%のBAを添加することでそれぞれ5分および0.5分の接触で4logTCID50感染価が減少し、アルキルベンジルジメチルアンモニウムクロライドとBAの併用により短時間で高い抗ウイルス効果を発揮することが確認された(表2)。同様にジデシルジメチルアンモニウムクロライド単独(0.05%)では5分で2.4logTCID50しか感染価が減少しないのに対して、ジデシルジメチルアンモニウムクロライド(0.05%)に0.5% BAを添加すると5分で、2% BAを添加したときは0.5分で4logTCID50の減少が確認された(表3)。このことから、本発明のカチオン性界面活性剤とBAは併用することで高いFCV不活化効果(ノロウイルス不活化効果)を短時間で発揮できることが示された。 (5) Test result It was confirmed that BA alone did not reduce the infectious titer of FCV by contact for 5 minutes (Table 1). Alkylbenzyldimethylammonium chloride alone (0.05%) reduces the infectivity only by 2.2 log TCID 50 after 5 minutes of FCV contact, compared to 1.0% for alkylbenzyldimethylammonium chloride (0.05%). % And 2.0% of BA reduces the 4 log TCID 50 infectivity in 5 minutes and 0.5 minutes of contact, respectively, and the combination of alkylbenzyldimethylammonium chloride and BA provides a high antiviral effect in a short time. It was confirmed that this was exhibited (Table 2). Similarly, didecyldimethylammonium chloride alone (0.05%) reduces the infectious value only by 2.4 log TCID 50 in 5 minutes, whereas didecyldimethylammonium chloride (0.05%) contains 0.5% BA. When 5% was added, a decrease of 4log TCID 50 was confirmed in 0.5 minutes when 2% BA was added (Table 3). From this, it was shown that the high FCV inactivation effect (norovirus inactivation effect) can be exhibited in a short time by using the cationic surfactant of the present invention and BA together.
BA単独では、5分間の接触でFCVの感染力価を減少させないことを確認した(表1)。アルキルベンジルジメチルアンモニウムクロライド単独(0.05%)では、FCVの5分間の接触で感染価を2.2logTCID50しか減少しないのに対し、アルキルベンジルジメチルアンモニウムクロライド(0.05%)に1.0%および2.0%のBAを添加することでそれぞれ5分および0.5分の接触で4logTCID50感染価が減少し、アルキルベンジルジメチルアンモニウムクロライドとBAの併用により短時間で高い抗ウイルス効果を発揮することが確認された(表2)。同様にジデシルジメチルアンモニウムクロライド単独(0.05%)では5分で2.4logTCID50しか感染価が減少しないのに対して、ジデシルジメチルアンモニウムクロライド(0.05%)に0.5% BAを添加すると5分で、2% BAを添加したときは0.5分で4logTCID50の減少が確認された(表3)。このことから、本発明のカチオン性界面活性剤とBAは併用することで高いFCV不活化効果(ノロウイルス不活化効果)を短時間で発揮できることが示された。 (5) Test result It was confirmed that BA alone did not reduce the infectious titer of FCV by contact for 5 minutes (Table 1). Alkylbenzyldimethylammonium chloride alone (0.05%) reduces the infectivity only by 2.2 log TCID 50 after 5 minutes of FCV contact, compared to 1.0% for alkylbenzyldimethylammonium chloride (0.05%). % And 2.0% of BA reduces the 4 log TCID 50 infectivity in 5 minutes and 0.5 minutes of contact, respectively, and the combination of alkylbenzyldimethylammonium chloride and BA provides a high antiviral effect in a short time. It was confirmed that this was exhibited (Table 2). Similarly, didecyldimethylammonium chloride alone (0.05%) reduces the infectious value only by 2.4 log TCID 50 in 5 minutes, whereas didecyldimethylammonium chloride (0.05%) contains 0.5% BA. When 5% was added, a decrease of 4log TCID 50 was confirmed in 0.5 minutes when 2% BA was added (Table 3). From this, it was shown that the high FCV inactivation effect (norovirus inactivation effect) can be exhibited in a short time by using the cationic surfactant of the present invention and BA together.
実施例2
(1)試験液の調製
(a)の第4級アンモニウム塩としてアルキルベンジルジメチルアンモニウムクロライド(サニゾールC(花王製)、直鎖アルキル(炭素数12~16の混合物)ベンジルジメチルアンモニウムクロライド)およびジデシルジメチルアンモニウムクロライド(DDAC;花王製)を、(b)としてベンジルアルコール(BA, (WAKO))を用いた。
(2)Novirus virus-like particles (NoV VLPs) 形状に対する評価試験方法
NoV VLPsはノロウイルスを構成するカプシドタンパク質を大量に発現させ、精製したものであり、カプシドタンパク質が自己集合することで、粒子構造をとっている。遺伝因子であるRNAを有していない以外は、形態学的にも免疫学的にもノロウイルスと同様であることが確認されている(Hansman, G. S., et al. Genetic and antigenic diversity among noroviruses. J. Gen. Virol. 87:909-919, 2006)。
NoV VLPsは、上記Hansman, G. S.らの方法に従い、バキュロウイルスを用いた組換えタンパク質の大量発現系を用いて作製した(非特許文献1)。即ち、バキュロウイルスのゲノムにNoV VLPsを構成する構造タンパク質をコードする遺伝子(accession No. AB365435)の構造タンパク質をコードする遺伝子領域をベクターに組み換え、組換えバキュロウイルスを作製し、昆虫細胞に感染させることで組換えタンパク質を大量に発現させ、NoV VLPsを回収・精製した。
表4、5、6に示した値の2倍濃度の試験液を作製し、NoV VLPs溶液と等量混合した。0.5,1,5分間接触させた後、30μLを抜き取り、試験液の除去操作を行った。即ち、抜き取った30μLをマイクロチューブに分取した360μLのSM-2 Bio-beads懸濁液(50% w/v)に接触させ、2分間攪拌した後、上清10μLをTEM観察に供した。SM-2 bio beadsは50(w/v)%になるように10mM HEPESに懸濁し、オートクレーブ滅菌したものを使用した。
接触試験後のNoV VLPsはTEM(Transmission Electron Microscope;透過型電子顕微鏡)観察に供試し、その粒子構造の変化を捉えることで各試験液の抗ノロウイルス効果を予想した。 Example 2
(1) Preparation of test solution Alkylbenzyldimethylammonium chloride (Sanisol C (manufactured by Kao), linear alkyl (mixture of 12 to 16 carbon atoms) benzyldimethylammonium chloride) and didecyl as the quaternary ammonium salt of (a) Dimethylammonium chloride (DDAC; manufactured by Kao) was used as benzyl alcohol (BA, (WAKO)) as (b).
(2) Novirus virus-like particles (NoV VLPs) Shape test method NoV VLPs are expressed and purified in large quantities of capsid proteins that compose norovirus. I'm taking it. It has been confirmed that morphologically and immunologically it is similar to norovirus except that it does not have RNA as a genetic factor (Hansman, GS, et al. Genetic and antigenic diversity among noroviruses. J Gen. Virol. 87: 909-919, 2006).
NoV VLPs were produced using a recombinant protein mass expression system using baculovirus according to the method of Hansman, G. S. et al. (Non-patent Document 1). That is, the gene region encoding the structural protein (accession No. AB365435) encoding the structural protein constituting NoV VLPs in the genome of baculovirus is recombined into a vector to produce a recombinant baculovirus and infect insect cells. As a result, the recombinant protein was expressed in large quantities, and NoV VLPs were recovered and purified.
Test solutions having a concentration twice the values shown in Tables 4, 5 and 6 were prepared and mixed in equal amounts with NoV VLPs solution. After contact for 0.5, 1, 5 minutes, 30 μL was extracted and the test solution was removed. Specifically, 30 μL extracted was brought into contact with 360 μL SM-2 Bio-beads suspension (50% w / v) dispensed in a microtube, stirred for 2 minutes, and then 10 μL of the supernatant was subjected to TEM observation. SM-2 bio beads were suspended in 10 mM HEPES so as to be 50 (w / v)% and autoclaved.
The NoV VLPs after the contact test were used for TEM (Transmission Electron Microscope) observation, and the anti-norovirus effect of each test solution was predicted by capturing changes in the particle structure.
(1)試験液の調製
(a)の第4級アンモニウム塩としてアルキルベンジルジメチルアンモニウムクロライド(サニゾールC(花王製)、直鎖アルキル(炭素数12~16の混合物)ベンジルジメチルアンモニウムクロライド)およびジデシルジメチルアンモニウムクロライド(DDAC;花王製)を、(b)としてベンジルアルコール(BA, (WAKO))を用いた。
(2)Novirus virus-like particles (NoV VLPs) 形状に対する評価試験方法
NoV VLPsはノロウイルスを構成するカプシドタンパク質を大量に発現させ、精製したものであり、カプシドタンパク質が自己集合することで、粒子構造をとっている。遺伝因子であるRNAを有していない以外は、形態学的にも免疫学的にもノロウイルスと同様であることが確認されている(Hansman, G. S., et al. Genetic and antigenic diversity among noroviruses. J. Gen. Virol. 87:909-919, 2006)。
NoV VLPsは、上記Hansman, G. S.らの方法に従い、バキュロウイルスを用いた組換えタンパク質の大量発現系を用いて作製した(非特許文献1)。即ち、バキュロウイルスのゲノムにNoV VLPsを構成する構造タンパク質をコードする遺伝子(accession No. AB365435)の構造タンパク質をコードする遺伝子領域をベクターに組み換え、組換えバキュロウイルスを作製し、昆虫細胞に感染させることで組換えタンパク質を大量に発現させ、NoV VLPsを回収・精製した。
表4、5、6に示した値の2倍濃度の試験液を作製し、NoV VLPs溶液と等量混合した。0.5,1,5分間接触させた後、30μLを抜き取り、試験液の除去操作を行った。即ち、抜き取った30μLをマイクロチューブに分取した360μLのSM-2 Bio-beads懸濁液(50% w/v)に接触させ、2分間攪拌した後、上清10μLをTEM観察に供した。SM-2 bio beadsは50(w/v)%になるように10mM HEPESに懸濁し、オートクレーブ滅菌したものを使用した。
接触試験後のNoV VLPsはTEM(Transmission Electron Microscope;透過型電子顕微鏡)観察に供試し、その粒子構造の変化を捉えることで各試験液の抗ノロウイルス効果を予想した。 Example 2
(1) Preparation of test solution Alkylbenzyldimethylammonium chloride (Sanisol C (manufactured by Kao), linear alkyl (mixture of 12 to 16 carbon atoms) benzyldimethylammonium chloride) and didecyl as the quaternary ammonium salt of (a) Dimethylammonium chloride (DDAC; manufactured by Kao) was used as benzyl alcohol (BA, (WAKO)) as (b).
(2) Novirus virus-like particles (NoV VLPs) Shape test method NoV VLPs are expressed and purified in large quantities of capsid proteins that compose norovirus. I'm taking it. It has been confirmed that morphologically and immunologically it is similar to norovirus except that it does not have RNA as a genetic factor (Hansman, GS, et al. Genetic and antigenic diversity among noroviruses. J Gen. Virol. 87: 909-919, 2006).
NoV VLPs were produced using a recombinant protein mass expression system using baculovirus according to the method of Hansman, G. S. et al. (Non-patent Document 1). That is, the gene region encoding the structural protein (accession No. AB365435) encoding the structural protein constituting NoV VLPs in the genome of baculovirus is recombined into a vector to produce a recombinant baculovirus and infect insect cells. As a result, the recombinant protein was expressed in large quantities, and NoV VLPs were recovered and purified.
Test solutions having a concentration twice the values shown in Tables 4, 5 and 6 were prepared and mixed in equal amounts with NoV VLPs solution. After contact for 0.5, 1, 5 minutes, 30 μL was extracted and the test solution was removed. Specifically, 30 μL extracted was brought into contact with 360 μL SM-2 Bio-beads suspension (50% w / v) dispensed in a microtube, stirred for 2 minutes, and then 10 μL of the supernatant was subjected to TEM observation. SM-2 bio beads were suspended in 10 mM HEPES so as to be 50 (w / v)% and autoclaved.
The NoV VLPs after the contact test were used for TEM (Transmission Electron Microscope) observation, and the anti-norovirus effect of each test solution was predicted by capturing changes in the particle structure.
(3)ネガティブ染色方法
TEM観察用のグリッドは、銅製コロジオン膜貼り付け400メッシュ(カーボン蒸着補強)(日新EM)を用い、使用直前にイオンスパッタ(E-1030:日立)にてクリーニングモードでグロー放電(1mA,30sec)を行い、グリッド表面野を親水化した。サンプル上清10μLを速やかにグリット上に滴下し、約3分後にキムタオルを用いてグリッド上の余分な水分をゆっくりと吸い取った。約1分間乾燥させ、次に、パラフィルム上に滴下しておいた染色液(2%リンタングステン酸溶液:pH6.8)にサンプル上清を吸着させたグリッド面を接触させ、約1分後にキムタオルを用いてグリッド上の余分な染色液をゆっくりと吸い取った。その後、0.45μmフィルターを通したイオン交換水10μLをグリッド上に滴下し、30秒間洗浄後、キムタオルを用いてグリッド上の余分な水分吸い取り、十分に乾燥させた。 (3) Negative staining method The grid for TEM observation is 400 mesh (carbon deposition reinforcement) with a copper collodion film (Nisshin EM), and in the cleaning mode by ion sputtering (E-1030: Hitachi) immediately before use. Glow discharge (1 mA, 30 sec) was performed to make the grid surface field hydrophilic. 10 μL of the sample supernatant was quickly dropped on the grit, and after about 3 minutes, excess water on the grid was slowly sucked off using a Kim towel. The sample was dried for about 1 minute, and then the grid surface on which the sample supernatant was adsorbed was brought into contact with a staining solution (2% phosphotungstic acid solution: pH 6.8) dripped on the parafilm. Using a Kim towel, the excess staining solution on the grid was slowly blotted out. Thereafter, 10 μL of ion-exchanged water passed through a 0.45 μm filter was dropped onto the grid, washed for 30 seconds, and then excess water on the grid was blotted using a Kim towel and dried sufficiently.
TEM観察用のグリッドは、銅製コロジオン膜貼り付け400メッシュ(カーボン蒸着補強)(日新EM)を用い、使用直前にイオンスパッタ(E-1030:日立)にてクリーニングモードでグロー放電(1mA,30sec)を行い、グリッド表面野を親水化した。サンプル上清10μLを速やかにグリット上に滴下し、約3分後にキムタオルを用いてグリッド上の余分な水分をゆっくりと吸い取った。約1分間乾燥させ、次に、パラフィルム上に滴下しておいた染色液(2%リンタングステン酸溶液:pH6.8)にサンプル上清を吸着させたグリッド面を接触させ、約1分後にキムタオルを用いてグリッド上の余分な染色液をゆっくりと吸い取った。その後、0.45μmフィルターを通したイオン交換水10μLをグリッド上に滴下し、30秒間洗浄後、キムタオルを用いてグリッド上の余分な水分吸い取り、十分に乾燥させた。 (3) Negative staining method The grid for TEM observation is 400 mesh (carbon deposition reinforcement) with a copper collodion film (Nisshin EM), and in the cleaning mode by ion sputtering (E-1030: Hitachi) immediately before use. Glow discharge (1 mA, 30 sec) was performed to make the grid surface field hydrophilic. 10 μL of the sample supernatant was quickly dropped on the grit, and after about 3 minutes, excess water on the grid was slowly sucked off using a Kim towel. The sample was dried for about 1 minute, and then the grid surface on which the sample supernatant was adsorbed was brought into contact with a staining solution (2% phosphotungstic acid solution: pH 6.8) dripped on the parafilm. Using a Kim towel, the excess staining solution on the grid was slowly blotted out. Thereafter, 10 μL of ion-exchanged water passed through a 0.45 μm filter was dropped onto the grid, washed for 30 seconds, and then excess water on the grid was blotted using a Kim towel and dried sufficiently.
(4)TEM観察方法
染色した試料は、透過型電子顕微鏡H7650(日立)を用いて、加圧電圧10kV、Emission Current 10μA、コンデンサーレンズ目盛りNo.2、対物レンズ目盛りNo.3の条件で速やかに観察した。 (4) TEM observation method A dyed sample was obtained by using a transmission electron microscope H7650 (Hitachi), a pressurization voltage of 10 kV, an emission current of 10 μA, a condenser lens scale No. 2, objective lens scale No. Observation was made promptly under the condition of 3.
染色した試料は、透過型電子顕微鏡H7650(日立)を用いて、加圧電圧10kV、Emission Current 10μA、コンデンサーレンズ目盛りNo.2、対物レンズ目盛りNo.3の条件で速やかに観察した。 (4) TEM observation method A dyed sample was obtained by using a transmission electron microscope H7650 (Hitachi), a pressurization voltage of 10 kV, an emission current of 10 μA, a condenser lens scale No. 2, objective lens scale No. Observation was made promptly under the condition of 3.
(5)TEM観察による粒子形状評価結果
- :効果が全く期待できない(粒子構造に変化無)
-/+:効果がほとんど期待できない(わずかに変形した粒子有)
+ :効果がわずかに期待できる(半数程度の粒子が変形)
++ :効果が期待できる(変形した粒子形状が大多数)
+++:顕著な効果が期待できる(変形した粒子のみ) (5) Results of particle shape evaluation by TEM observation-: No effect can be expected (no change in particle structure)
-/ +: Little effect expected (with slightly deformed particles)
+: Slight effect can be expected (about half of the particles are deformed)
++: An effect can be expected (the majority of deformed particle shapes)
+++: Significant effect can be expected (only deformed particles)
- :効果が全く期待できない(粒子構造に変化無)
-/+:効果がほとんど期待できない(わずかに変形した粒子有)
+ :効果がわずかに期待できる(半数程度の粒子が変形)
++ :効果が期待できる(変形した粒子形状が大多数)
+++:顕著な効果が期待できる(変形した粒子のみ) (5) Results of particle shape evaluation by TEM observation-: No effect can be expected (no change in particle structure)
-/ +: Little effect expected (with slightly deformed particles)
+: Slight effect can be expected (about half of the particles are deformed)
++: An effect can be expected (the majority of deformed particle shapes)
+++: Significant effect can be expected (only deformed particles)
BA単独で5分間の接触ではNoV VLPsの粒子構造が全く変化しないことが確認された(表4)。アルキルベンジルジメチルアンモニウムクロライド単独(0.05%)では5分間の接触でわずかにNoV VLPsの粒子構造の変形が確認されるのに対し、アルキルベンジルジメチルアンモニウムクロライド(0.05%)に0.5%,1.0%,2.0%のBAを添加することで各々5,1,0.5分の接触で効果が期待できる程度の粒子形状の変化が確認され、抗菌剤/溶剤の併用によりノロウイルスに対しても短時間で抗ウイルス効果を発揮することが示唆された(表5)。同様にジデシルジメチルアンモニウムクロライド(DDAC)単独(0.05%)では効果がわずかに期待できる程度しか粒子形状の変化が観察されなかったのに対して、DDAC(0.05%)にBAを0.5%を添加すると1分で、さらに2.0%のBAを添加したときは0.5分で効果が期待できる程度の粒子形状の変化が観察された(表6)。このことから、カチオン性界面活性剤とBAは併用することで抗ノロウイルス効果を短時間で発揮できることが示唆された。
サニゾールC (0.05%)及びBA(2.00%)を0.5分添加した場合のTEM写真を図1に示した。図1より、アルキルベンジルジメチルアンモニウム塩及びベンジルアルコールを併用して作用させたことで、ノロウイルスの構造タンパク質のみで構成されたNorovirus virus like particles (NoV VLPs) の粒子構造が変形した状態が確認された。 It was confirmed that the particle structure of NoV VLPs did not change at all by contact with BA alone for 5 minutes (Table 4). Alkylbenzyldimethylammonium chloride alone (0.05%) shows slight deformation of the particle structure of NoV VLPs after 5 minutes of contact, whereas alkylbenzyldimethylammonium chloride (0.05%) has 0.5% %, 1.0%, and 2.0% of BA added to confirm the change in particle shape to the extent that the effect can be expected by contact for 5, 1 and 0.5 minutes, respectively. It was suggested that the antiviral effect was exhibited in a short time against Norovirus (Table 5). Similarly, with didecyldimethylammonium chloride (DDAC) alone (0.05%), only a slight change in particle shape was observed, whereas BA was added to DDAC (0.05%). When 0.5% was added, 1 minute was observed, and when 2.0% BA was further added, a change in the particle shape was observed to such an extent that an effect could be expected in 0.5 minutes (Table 6). This suggests that the anti-norovirus effect can be exhibited in a short time by using a cationic surfactant and BA in combination.
FIG. 1 shows a TEM photograph when Sanisole C (0.05%) and BA (2.00%) were added for 0.5 minutes. From FIG. 1, it was confirmed that the particle structure of Norovirus virus like particles (NoV VLPs) composed only of norovirus structural proteins was deformed by the combined action of alkylbenzyldimethylammonium salt and benzyl alcohol. .
サニゾールC (0.05%)及びBA(2.00%)を0.5分添加した場合のTEM写真を図1に示した。図1より、アルキルベンジルジメチルアンモニウム塩及びベンジルアルコールを併用して作用させたことで、ノロウイルスの構造タンパク質のみで構成されたNorovirus virus like particles (NoV VLPs) の粒子構造が変形した状態が確認された。 It was confirmed that the particle structure of NoV VLPs did not change at all by contact with BA alone for 5 minutes (Table 4). Alkylbenzyldimethylammonium chloride alone (0.05%) shows slight deformation of the particle structure of NoV VLPs after 5 minutes of contact, whereas alkylbenzyldimethylammonium chloride (0.05%) has 0.5% %, 1.0%, and 2.0% of BA added to confirm the change in particle shape to the extent that the effect can be expected by contact for 5, 1 and 0.5 minutes, respectively. It was suggested that the antiviral effect was exhibited in a short time against Norovirus (Table 5). Similarly, with didecyldimethylammonium chloride (DDAC) alone (0.05%), only a slight change in particle shape was observed, whereas BA was added to DDAC (0.05%). When 0.5% was added, 1 minute was observed, and when 2.0% BA was further added, a change in the particle shape was observed to such an extent that an effect could be expected in 0.5 minutes (Table 6). This suggests that the anti-norovirus effect can be exhibited in a short time by using a cationic surfactant and BA in combination.
FIG. 1 shows a TEM photograph when Sanisole C (0.05%) and BA (2.00%) were added for 0.5 minutes. From FIG. 1, it was confirmed that the particle structure of Norovirus virus like particles (NoV VLPs) composed only of norovirus structural proteins was deformed by the combined action of alkylbenzyldimethylammonium salt and benzyl alcohol. .
Claims (14)
- 次の成分(A)及び(B)を含有する抗ウイルス剤組成物。
(A)ジアルキルジメチルアンモニウム塩及びアルキルベンジルジメチルアンモニウム塩から選ばれる1種以上の第4級アンモニウム塩 0.05vol%以上0.5vol%以下
(B)ベンジルアルコール 0.5vol%以上2vol%以下 An antiviral composition containing the following components (A) and (B).
(A) One or more quaternary ammonium salts selected from dialkyldimethylammonium salts and alkylbenzyldimethylammonium salts 0.05 vol% to 0.5 vol% (B) benzyl alcohol 0.5 vol% to 2 vol% - (A)の第4級アンモニウム塩が、ドデシルベンジルジメチルアンモニウムクロライド、テトラデシルベンジルジメチルアンモニウムクロライド、ヘキサデシルベンジルジメチルアンモニウムクロライド及びジデシルジメチルアンモニウムクロライドから選ばれる1種以上である請求項1に記載の組成物。 The quaternary ammonium salt of (A) is at least one selected from dodecylbenzyldimethylammonium chloride, tetradecylbenzyldimethylammonium chloride, hexadecylbenzyldimethylammonium chloride and didecyldimethylammonium chloride. Composition.
- ウイルスが非エンベロープ型ウイルスである請求項1又は2に記載の組成物。 The composition according to claim 1 or 2, wherein the virus is a non-enveloped virus.
- ウイルスがノロウイルス属に属するウイルスである請求項1又は2に記載の組成物。 The composition according to claim 1 or 2, wherein the virus is a virus belonging to the genus Norovirus.
- 次の成分(A)及び(B)を含有する組成物を用いるウイルス不活化方法。
(A)ジアルキルジメチルアンモニウム塩及びアルキルベンジルジメチルアンモニウム塩から選ばれる1種以上の第4級アンモニウム塩 0.05vol%以上0.5vol%以下
(B)ベンジルアルコール 0.5vol%以上2vol%以下 A virus inactivation method using a composition containing the following components (A) and (B).
(A) One or more quaternary ammonium salts selected from dialkyldimethylammonium salts and alkylbenzyldimethylammonium salts 0.05 vol% to 0.5 vol% (B) benzyl alcohol 0.5 vol% to 2 vol% - (A)の第4級アンモニウム塩が、ドデシルベンジルジメチルアンモニウムクロライド、テトラデシルベンジルジメチルアンモニウムクロライド、ヘキサデシルベンジルジメチルアンモニウムクロライド及びジデシルジメチルアンモニウムクロライドから選ばれる1種以上である請求項5に記載の方法。 The quaternary ammonium salt of (A) is at least one selected from dodecylbenzyldimethylammonium chloride, tetradecylbenzyldimethylammonium chloride, hexadecylbenzyldimethylammonium chloride and didecyldimethylammonium chloride. Method.
- ウイルスが非エンベロープ型ウイルスである請求項5又は6に記載の方法。 The method according to claim 5 or 6, wherein the virus is a non-enveloped virus.
- ウイルスがノロウイルス属に属するウイルスである請求項5又は6に記載の方法。 The method according to claim 5 or 6, wherein the virus is a virus belonging to the genus Norovirus.
- ウイルス不活化のための、次の成分(A)及び(B)を含有する組成物の使用。
(A)ジアルキルジメチルアンモニウム塩及びアルキルベンジルジメチルアンモニウム塩から選ばれる1種以上の第4級アンモニウム塩 0.05vol%以上0.5vol%以下
(B)ベンジルアルコール 0.5vol%以上2vol%以下 Use of a composition containing the following components (A) and (B) for virus inactivation:
(A) One or more quaternary ammonium salts selected from dialkyldimethylammonium salts and alkylbenzyldimethylammonium salts 0.05 vol% to 0.5 vol% (B) benzyl alcohol 0.5 vol% to 2 vol% - (A)の第4級アンモニウム塩が、ドデシルベンジルジメチルアンモニウムクロライド、テトラデシルベンジルジメチルアンモニウムクロライド、ヘキサデシルベンジルジメチルアンモニウムクロライド及びジデシルジメチルアンモニウムクロライドから選ばれる1種以上である請求項9に記載の使用。 The quaternary ammonium salt of (A) is at least one selected from dodecylbenzyldimethylammonium chloride, tetradecylbenzyldimethylammonium chloride, hexadecylbenzyldimethylammonium chloride and didecyldimethylammonium chloride. use.
- ウイルスが非エンベロープ型ウイルスである請求項9又は10に記載の使用。 The use according to claim 9 or 10, wherein the virus is a non-enveloped virus.
- ウイルスがノロウイルス属に属するウイルスである請求項9又は10に記載の使用。 The use according to claim 9 or 10, wherein the virus is a virus belonging to the genus Norovirus.
- (A)ジアルキルジメチルアンモニウム塩及びアルキルベンジルジメチルアンモニウム塩から選ばれる1種以上の第4級アンモニウム塩に、(B)ベンジルアルコールを併用することを特徴とする、前記第4級アンモニウム塩のウイルス不活化効果の増強方法。 (A) One or more quaternary ammonium salts selected from dialkyldimethylammonium salts and alkylbenzyldimethylammonium salts are used in combination with (B) benzyl alcohol. A method for enhancing the activation effect.
- (A)ジアルキルジメチルアンモニウム塩及びアルキルベンジルジメチルアンモニウム塩から選ばれる1種以上の第4級アンモニウム塩のウイルス不活化効果を増強するための、前記(A)の第4級アンモニウム塩と併用する(B)ベンジルアルコールの使用。 (A) In combination with the quaternary ammonium salt of (A) above for enhancing the virus inactivating effect of one or more quaternary ammonium salts selected from dialkyldimethylammonium salts and alkylbenzyldimethylammonium salts ( B) Use of benzyl alcohol.
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---|---|---|---|---|
CN111455655A (en) * | 2020-04-24 | 2020-07-28 | 广东溢达纺织有限公司 | Antiviral fabric and preparation method thereof |
WO2020210789A1 (en) * | 2019-04-12 | 2020-10-15 | Ecolab Usa Inc. | Hard surface cleaning solution with rapid viricidal activity |
CN112546034A (en) * | 2020-12-18 | 2021-03-26 | 上海海禾医疗科技有限公司 | Virus-inactivating wash-free foam type disinfectant |
CN112618525A (en) * | 2020-12-18 | 2021-04-09 | 上海海禾医疗科技有限公司 | Disinfectant for quickly inactivating coronavirus |
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JP6574119B2 (en) * | 2015-08-31 | 2019-09-11 | 大王製紙株式会社 | Norovirus inactivation evaluation method |
JP7022216B2 (en) * | 2018-07-27 | 2022-02-17 | 富士フイルム株式会社 | Antiviral compositions, antinorovirus compositions, sprays, wipers, compounds |
WO2023145619A1 (en) * | 2022-01-31 | 2023-08-03 | 花王株式会社 | Non-enveloped virus inactivation composition |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH03163007A (en) * | 1989-08-22 | 1991-07-15 | Eastman Kodak Co | Anti-microbial composition |
US20090191288A1 (en) * | 1996-02-12 | 2009-07-30 | Squires Meryl J | Composition to Treat Herpes, Pseudomonas, Staph, Hepatitis and Other Infectious Diseases |
WO2011002929A1 (en) * | 2009-06-30 | 2011-01-06 | The Trustees Of Columbia University In The City Of New York | Antimicrobial/preservative compositions comprising botanicals |
-
2012
- 2012-07-18 JP JP2012159593A patent/JP2013040167A/en active Pending
- 2012-07-18 WO PCT/JP2012/068213 patent/WO2013012007A1/en active Application Filing
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH03163007A (en) * | 1989-08-22 | 1991-07-15 | Eastman Kodak Co | Anti-microbial composition |
US20090191288A1 (en) * | 1996-02-12 | 2009-07-30 | Squires Meryl J | Composition to Treat Herpes, Pseudomonas, Staph, Hepatitis and Other Infectious Diseases |
WO2011002929A1 (en) * | 2009-06-30 | 2011-01-06 | The Trustees Of Columbia University In The City Of New York | Antimicrobial/preservative compositions comprising botanicals |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2020210789A1 (en) * | 2019-04-12 | 2020-10-15 | Ecolab Usa Inc. | Hard surface cleaning solution with rapid viricidal activity |
AU2020271558B2 (en) * | 2019-04-12 | 2023-03-02 | Ecolab Usa Inc. | Hard surface cleaning solution with rapid viricidal activity |
CN111455655A (en) * | 2020-04-24 | 2020-07-28 | 广东溢达纺织有限公司 | Antiviral fabric and preparation method thereof |
CN112546034A (en) * | 2020-12-18 | 2021-03-26 | 上海海禾医疗科技有限公司 | Virus-inactivating wash-free foam type disinfectant |
CN112618525A (en) * | 2020-12-18 | 2021-04-09 | 上海海禾医疗科技有限公司 | Disinfectant for quickly inactivating coronavirus |
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