Virus inactivator and virus inactivation method

Abstract

The purpose of the present invention is to provide a novel virus inactivating agent and a virus inactivation method. The virus inactivating agent and virus inactivation method of the present invention have a decomposed product of an azodicarbonamide as an active ingredient.

Description

Technical Field

[0001] The present invention relates to a virus inactivator and a virus inactivation method.

Background Art

[0002] Conventionally, various agents have been known as bactericides for bacteria, virus inactivators, etc., and their usage modes are also various. For example, Patent Document 1 discloses an air disinfection composition containing glycol ether as a disinfectant for microorganisms such as molds, yeasts, viruses, and bacteria present in the air in a closed space such as a room, and it is described that the above microorganisms can be disinfected by volatilizing the composition into the space. Further, Patent Document 2 discloses a disinfectant such as benzalkonium chloride as a disinfectant for microorganisms such as molds that float in the air or adhere to furniture and multiply, and methods such as storing the disinfectant in a pressure spray container and spraying it are described. Also, Patent Document 3 discloses a space disinfection tool that disinfects bacteria and viruses present in a space by releasing chlorine dioxide into the space.

[0003] On the other hand, azodicarbonamide is known as a kind of organic foaming agent, and Patent Document 4 describes a foaming agent composition containing azodicarbonamide as an organic foaming agent.

Prior Art Documents

Patent Documents

[0004]

Patent Document 1

Patent Document 2

Patent Document 3

Patent Document 4

Summary of the Invention

Problems to be Solved by the Invention

[0005] As described in Patent Documents 1 to 3 above, various agents have hitherto been known as bactericidal agents for bacteria and inactivating agents for viruses. Therefore, an object of the present invention is to provide a novel virus inactivating agent and a novel virus inactivating method different from the above agents.

Means for Solving the Problems

[0006] The present inventors have found that the decomposition product of azodicarbonamide acts effectively as a virus inactivating agent. Conventionally, azodicarbonamide has been known as one of the organic foaming agents used in the rubber and plastic industries because it causes a foaming action when thermally decomposed by heating. Also in the foaming agent composition described in Patent Document 4 above, azodicarbonamide is used as an organic foaming agent.

[0007] Thus, it has been well known that azodicarbonamide can be used as an organic foaming agent. However, as a result of intensive research on azodicarbonamide by the present inventors this time, surprisingly, it has been newly found that the decomposition product of azodicarbonamide acts effectively as a virus inactivating agent having a good virus inactivating effect on viruses, and the present invention has been completed.

[0008] That is, the present invention is as follows. (1) A virus inactivating agent containing a decomposition product of azodicarbonamide as an active ingredient. (2) The virus inactivating agent according to (1) above, wherein the decomposition product of azodicarbonamide is a decomposition product generated within 30 minutes immediately after the start of heating of azodicarbonamide. (3) A virus inactivating method using a decomposition product of azodicarbonamide as an active ingredient. (4) Heating azodicarbonamide at a heating temperature of 200 °C or higher to generate a decomposition product of the azodicarbonamide, the virus inactivation method according to (3) above. (5) The virus inactivation method according to (4) above, which is heated by a hydrothermal heating system. (6) Heating the azodicarbonamide in the range of 0.1 to 2 g with respect to a space of 1 m 3 The virus inactivation method according to (4) or (5) above.

Advantages of the Invention

[0009] According to the present invention, the decomposition product of azodicarbonamide can exhibit a good virus inactivation effect on viruses.

Brief Description of the Drawings

[0010]

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Embodiments for Carrying Out the Invention

[0011] The virus inactivator of the present invention is a virus inactivator containing a decomposition product of azodicarbonamide as an active ingredient. Hereinafter, the virus inactivator of the present invention will be described in more detail.

[0012] The decomposition product of azodicarbonamide, which is the active ingredient of the virus inactivator of the present invention, can be obtained, for example, by heating azodicarbonamide. Azodicarbonamide is a kind of organic foaming agent used in the rubber and plastic industries as described above, and commercially available products or those synthesized by known methods can be used. Examples of commercially available products include "Uniform AZ" (trade name) manufactured by Otsuka Chemical Co., Ltd., "Cellmic" (trade name) manufactured by Sankyo Kasei Co., Ltd., and the like.

[0013] Azodicarbonamide has a decomposition start temperature of about 200°C, a large amount of gas generated during decomposition, and excellent diffusibility. When azodicarbonamide is thermally decomposed by heating, a foaming action occurs and decomposition products of azodicarbonamide are generated. These decomposition products of azodicarbonamide are generated as decomposition products in three states: gaseous, liquid (including misty), and solid. Among them, the decomposition products of azodicarbonamide are divided into decomposition products floating in the air mainly composed of gaseous and misty decomposition products (hereinafter referred to as floating substances) and decomposition products falling due to their own weight mainly composed of solid decomposition products (hereinafter referred to as falling substances).

[0014] The decomposition products of azodicarbonamide having an effective virus inactivating effect of the present invention are presumed to be composed of floating substances that are generated during the decomposition of azodicarbonamide and float in the air and falling substances that fall due to their own weight, as described above. From the study by the present inventors, as shown in the following examples, it is presumed that among these decomposition products of azodicarbonamide, the floating substances exhibit a particularly good virus inactivating effect against viruses. In addition, from the viewpoint of the virus inactivating effect, it is preferable that the above floating substances are generated within 30 minutes after the start of heating of azodicarbonamide. More preferably, the floating substances generated immediately after the start of heating of azodicarbonamide are more preferable. In this specification, "immediately after the start of heating" means less than 5 minutes after the start of heating. For example, when heating is carried out using a hydrolysis heating system, it is usually possible to confirm the generation of smoke within less than 5 minutes after the start of heating, and it can be seen that azodicarbonamide decomposes and its decomposition products scatter.

[0015] In the present invention, although the mechanism by which the decomposition product of azodicarbonamide exerts a good inactivating effect on viruses is not clear, it is presumed that the decomposition product of azodicarbonamide denatures the protein shell that surrounds the nucleic acid of the virus.

[0016] From the viewpoint of better virus inactivating effect, the heating temperature for decomposing azodicarbonamide is preferably 200°C or higher, more preferably 200 - 700°C, and even more preferably 300 - 500°C.

[0017] The heating means for decomposing azodicarbonamide is not particularly limited as long as the decomposition product of azodicarbonamide as the active ingredient can be obtained. For example, methods such as directly igniting and heating, contacting with a heat source such as a heater and heating, and heating using a heat source such as a heating agent can be mentioned. Among them, from the viewpoints of ease of handling and efficient volatility of the decomposition product of azodicarbonamide, the method of heating using a heat source such as a heating agent is preferred, and it is more preferred to use a chemical heating system that generates heat using a chemical exothermic substance and a liquid for chemical exothermic reaction as the heat source. When using a chemical heating system, the heating temperature of 200°C or higher can be reached in a short time, so that the decomposition product of azodicarbonamide (the active ingredient of the virus inactivator of the present invention) can be efficiently generated and volatilized, and a large amount of the decomposition product of azodicarbonamide can be diffused to the application site (for example, indoors, etc.).

[0018] As the heating conditions for better exerting this effect, it is preferable to heat azodicarbonamide so that the time when the temperature is 100°C or higher is 700 seconds or more, more preferably 800 seconds or more, and even more preferably 900 seconds or more. Also, it is preferable that the time when the temperature is 200°C or higher is 250 seconds or more, more preferably 300 seconds or more, and even more preferably 350 seconds or more. Also, the time during which the temperature is 250°C or higher is preferably 200 seconds or more, and more preferably 300 seconds or more. Also, the time during which the temperature is 300°C or higher is preferably 150 seconds or more, and more preferably 200 seconds or more. Also, the time during which the temperature is 350°C or higher is preferably 130 seconds or more, and more preferably 150 seconds or more.

[0019] As heating conditions for preferably exhibiting this effect, during the period from the start of heating to the end of heating, when the heating temperature is measured at 1-second intervals, the total sum of the temperatures that reach 100°C or higher is preferably 140,000 °C·s or more, more preferably 170,000 °C·s or more, and even more preferably 200,000 °C·s or more. Also, the total sum of the temperatures that reach 200°C or higher is preferably 70,000 °C·s or more, more preferably 90,000 °C·s or more, and even more preferably 120,000 °C·s or more. Also, the total sum of the temperatures that reach 250°C or higher is preferably 60,000 °C·s or more, more preferably 80,000 °C·s or more, and even more preferably 100,000 °C·s or more. Also, the total sum of the temperatures that reach 300°C or higher is preferably 40,000 °C·s or more, more preferably 60,000 °C·s or more, and even more preferably 80,000 °C·s or more. Also, the total sum of the temperatures that reach 350°C or higher is preferably 30,000 °C·s or more, more preferably 45,000 °C·s or more, and even more preferably 60,000 °C·s or more.

[0020] As an example of a heating means for azodicarbonamide, the means for heating azodicarbonamide using a water-releasing heating system will be described below. A water-releasing heating system is a system in which a water-releasing heating substance and a liquid for a water-releasing heating reaction are subjected to a water-releasing heating reaction, and the heat source in this system is the self-heating device 1 shown in FIG. 1.

[0021] As shown in FIG. 1, the interior of the self-heating device 1 is partitioned into two spaces, an outer space and an inner space, by a bottomed partition member 4. The outer side of the partition member 4 is filled with a water-adding heating substance 8, and the inner side of the partition member 4 houses a preparation 7 (virus inactivator) containing azodicarbonamide. When the self-heating device 1 is immersed in the water-adding heating reaction liquid W, the water-adding heating reaction liquid W that has entered the device from the bottom of the self-heating device 1 reacts with the water-adding heating substance 8 to generate reaction heat. The azodicarbonamide is heated using the reaction heat generated by the water-adding heating reaction, and decomposition products of azodicarbonamide, which are the active ingredients of the virus inactivator of the present invention, are generated and volatilized.

[0022] The water-adding heating substance 8 is a substance that self-heats by reacting with the water-adding heating reaction liquid W. Examples thereof include calcium oxide (quicklime), magnesium chloride, aluminum chloride, and the like. Examples of the water-adding heating reaction liquid W include water or a liquid obtained by adding various additives to water. The additives do not prevent the volatilization of the decomposition products of azodicarbonamide and do not reduce the reactivity of water with the heating substance. Specifically, organic solvents and liquid stabilizers can be mentioned.

[0023] In the present invention, for example, when the self-heating device 1 is used as a heat source, the heating temperature of azodicarbonamide can be obtained by measuring the temperature of the bottom X of the partition member 4 shown in FIG. 1.

[0024] In addition to heating by the exothermic system with water addition, for example, an electric heating system using a heating wire such as nichrome wire, a flat or ring-shaped heating heater, or a heating heater using a semiconductor; mixing iron powder with an oxidizing agent such as ammonium chlorate, mixing a metal with a metal oxide or oxidizing agent having a smaller ionization tendency than the metal, contacting a mixture of iron and potassium sulfate, iron sulfate, metal chloride, iron sulfide, etc. with water or oxygen, contacting a mixture of a metal having a larger ionization tendency than iron and a halide of a metal having a smaller ionization tendency than iron with water, contacting a mixture of a metal and bisulfate with water, adding water to a mixture of aluminum and an alkali metal nitrate, etc., a system that generates heat by an oxidation reaction such as this can also be used for heating.

[0025] In addition to the decomposition products of azodicarbonamide, the virus inactivator of the present invention may contain any components as long as the effects of the present invention are achieved. As optional components, for example, bactericides, antibacterial agents, fragrances, solvents, deodorants, volatilization aids, stabilizers, insecticides, pest repellents, etc. can be used.

[0026] Examples of bactericides and antibacterial agents include phenolic bactericides such as triclosan and isopropylmethylphenol; carbamide bactericides such as trichlorocarbanilide; pyridine bactericides such as zinc pyrithione; cationic bactericides such as cetylpyridinium chloride and benzalkonium chloride, amine bactericides such as trialkyltriamine, etc.; imidazole bactericides such as enilconazole; organic iodine bactericides such as 3-iodo-2-propynyl-n-butylcarbamate (IPBC); one or more of silver zeolite and the like.

[0027] Examples of fragrances include natural fragrances extracted from various plants and animals, synthetic fragrances chemically synthesized, and compound fragrances made by mixing a large number of these fragrance components. Fragrances that can be used are those described in various documents, such as "Perfume and Flavor Materials of Natural Origin", Steffen Arctander, Allured Pub. Co. (1960); "Encyclopedia of Scents", edited by the Japan Flavor Association, Asakura Shoten (1989); "Flower oils and Floral Compounds In Perfumery", Danute Pajaujis Anonis, Allured Pub. Co. (1993); "Perfume and Flavor Chemicals (aroma chemicals)", Vols. I and II, Steffen Arctander, Allured Pub. Co. (1994); "Basic Knowledge of Fragrances and Perfumery", edited by Motoki Nakajima, Sangyo Tosho (1995); "Synthetic Fragrances - Chemistry and Product Knowledge", written by Motokazu Indoh, Chemical Industry Nippo Co., Ltd. (1996); "Encyclopedia Dictionary of Scents", edited by Mitsukazu Tanigai, Maruzen (2005). By citing each of them, it is made part of the disclosure of this specification. Specific representative examples of fragrances are given below, but are not limited thereto.

[0028] Examples of natural fragrances include natural essential oils such as orange oil, lemon oil, lavender oil, lavandin oil, bergamot oil, patchouli oil, cypress oil, peppermint oil, thyme oil, clove oil, cinnamon oil, eucalyptus oil, tea tree oil, and the like. Examples of synthetic fragrances include hydrocarbon terpenes such as α-pinene, β-pinene, limonene, p-cymene, terpinolene, α-terpinene, γ-terpinene, α-farnesene, camphene, etc.; aldehydes such as heptanal, octanal, decanal, benzaldehyde, salicylic aldehyde, phenylacetaldehyde, citronellal, hydroxycitronellal, citral, α-hexylcinnamic aldehyde, linalool, cyclamen aldehyde, lilial, heliotropin, helional, vanillin, ethylvanillin, etc.; esters and lactones such as ethyl formate, methyl acetate, methyl propionate, methyl isobutyrate, propyl butyrate, isobutyl acetate, isobutyl butyrate, isobutyl isovalerate, ethyl-2-methylvalerate, isoamyl acetate, amyl propionate, allyl hexanoate, ethyl acetoacetate, ethyl heptylate, methyl benzoate, ethyl benzoate, ethyl octylate, benzyl acetate, nonyl acetate, ortho-tert-butylcyclohexyl acetate, linalyl benzoate, ethyl cinnamate, methyl salicylate, hexyl salicylate, hexyl butyrate, menthyl acetate, terpinyl acetate, phenylethyl isobutyrate, methyl jasmonate, methyl dihydrojasmonate, ethylene brassylate, γ-undecalactone, γ-nonanolactone, cyclopentadecanolide, coumarin, etc.; ethers such as anisole, p-cresyl methyl ether, dimethylhydroquinone, methyl eugenol, β-naphthol methyl ether, β-naphthol ethyl ether, anethole, diphenyl oxide, rose oxide, galaxolide, ambrox; alcohols such as isopropyl alcohol, cis-3-hexenol, heptanol, 2-octanol, dimethol, dihydromyrcenol, linalool, benzyl alcohol, citronellol, geraniol, nerol, terpineol, l-menthol, cedrol, thymol, anisyl alcohol, phenylethyl alcohol, hexanol, etc.Ketones such as diacetyl, menthone, isomenthone, acetophenone, α- or β-damascone, α- or β-damascenone, α-, β- or γ-ionone, α-, β- or γ-methylionone, methyl-β-naphthyl ketone, benzophenone, tentarome, acetyl cedrene, α- or β-isomethylionone, α-, β- or γ-iron, maltol, cis-jasmone, dihydrojasmone, l-carvone, dihydrocarvone, methyl amyl ketone, etc.; camphor, 1,8-cineole, allyl amyl glycolate, isopulegol, ligustral, allyl caproate, etc. can be mentioned.; These fragrances can be used alone or in any combination of two or more as compounded fragrances. Furthermore, the fragrance can also be used as a mixture (fragrance composition) containing fragrance components, solvents, fragrance stabilizers, etc.

[0029] Examples of the solvent include alcohols such as water, ethanol, propanol, and benzyl alcohol; polyhydric alcohols such as ethylene glycol, diethylene glycol, dipropylene glycol, glycerin, and 1,3 - butanediol; glycol ethers such as ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, ethylene glycol monopropyl ether, ethylene glycol monobutyl ether, diethylene glycol monomethyl ether, diethylene glycol monoethyl ether, diethylene glycol monopropyl ether, diethylene glycol monobutyl ether, diethylene glycol mono - isobutyl ether, triethylene glycol monobutyl ether, propylene glycol monomethyl ether, propylene glycol dimethyl ether, dipropylene glycol monomethyl ether, tripropylene glycol monomethyl ether, tripropylene glycol monobutyl ether, propylene glycol monopropyl ether, dipropylene glycol monopropyl ether, propylene glycol monobutyl ether, propylene glycol - tert - butyl ether, dipropylene glycol monobutyl ether, dipropylene glycol dimethyl ether, phenyl carbitol, phenyl cellosolve, and benzyl carbitol; paraffins such as liquid paraffin and n - paraffin; esters such as diethyl phthalate, benzyl benzoate, triethyl citrate, and isopropyl myristate; and others such as 3 - methyl - 4 - methoxybutanol, N - methylpyrrolidone, and propylene carbonate. These solvents can be used alone or in any combination of two or more. They can also be mixed with the above - mentioned fragrance components and used as a fragrance composition.

[0030] The fragrance can be appropriately contained in the virus inactivator of the present invention so as to achieve a predetermined balance. The fragrance is preferably contained in the virus inactivator in an amount of 0.01 to 20% by mass, more preferably 0.1 to 10% by mass. When the fragrance is contained, if the content is less than 0.01% by mass, sufficient fragrance intensity may not be obtained, and if it exceeds 20% by mass, the fragrance may be too strong. In addition, when volatilizing the fragrance into the space together with the decomposition product of azodicarbonamide, it is preferably contained in the virus inactivator of the present invention so that the volatilization concentration of the fragrance becomes 1 to 300 mg / m 3 and more preferably contained so as to be 5 to 150 mg / m 3 By setting it within the above range, the virus inactivating effect can be synergistically enhanced with the decomposition product of azodicarbonamide. In addition, it is possible to suppress the unpleasant odor generated when volatilizing azodicarbonamide and enhance the actual feeling of use.

[0031] Examples of the deodorant include lauryl methacrylate, geranyl crotonate, catechin, polyphenol, charcoal, and the like.

[0032] Examples of the volatilization aid include zinc stearate, aluminum stearate, barium stearate, calcium stearate, zinc carbonate, calcium carbonate, titanium dioxide, carbon black, antimony trioxide, decabromodiphenylene oxide, trimellitic anhydride, maleic anhydride, benzotriazole, 4,4'-oxybis(benzenesulfonyl hydrazide), urea, and the like.

[0033] Examples of the stabilizer include dibutylhydroxytoluene, butylhydroxyanisole, tocopherol, and the like.

[0034] Examples of the insecticide include pyrethroid insecticides such as natural pyrethrin, pyrethrin, allethrin, phthalothrin, resmethrin, flumethrin, permethrin, phenothrin, silafluofen, etc.; carbamate insecticides such as propoxur, carbaryl, etc.; organophosphorus insecticides such as fenitrothion, DDVP, etc.; oxadiazole insecticides such as methoxadiazone, etc.; phenylpyrazole insecticides such as fipronil, etc.; neonicotinoid insecticides such as imidacloprid, dinotefuran, etc.; sulfonamide insecticides such as amidoflumet, etc.; benzamide insecticides such as broflanilide, etc.; pyrrole compounds such as chlorfenapyr, etc.; insect juvenile hormone-like compounds such as methoprene, hydroprene, etc.; anti-juvenile hormone-like compounds such as precocene, etc.; ecdyson-like compounds such as ecdyson, etc.; essential oils such as phytolaccoside, peppermint oil, orange oil, cinnamon oil, clove oil, etc.; and one or more of IBTA, IBTE, quaternary ammonium salts, benzyl salicylate, etc. Among them, pyrethroid insecticides, carbamate insecticides, oxadiazole insecticides and sulfonamide insecticides are preferable because their volatilization is improved, and particularly, phenothrin, silafluofen, permethrin, methoxadiazone, propoxur, amidoflumet, etofenprox are preferable.

[0035] Examples of the pest repellent include one or more of diet, di-n-butyl succinate, hydroxyanisole, rotenone, ethyl-butylacetylaminopropionate, ikaridin, ethyl 3-(N-n-butyl-N-acetyl)aminopropionate, etc.

[0036] In the present invention, "virus inactivation" means removing or significantly reducing the infectivity or growth ability of a virus, and also reducing the virus that can grow from an object (for example, the ceiling, wall, floor surface, etc. indoors).

[0037] In the present invention, the viruses to be inactivated are not particularly limited, and various viruses can be mentioned regardless of the type of genome, the presence or absence of an envelope, etc. In addition, the targets to be inactivated also include bacteriophages, which are viruses that infect bacteria. Examples of viruses include influenza virus, SARS coronavirus, MERS coronavirus, human coronavirus, feline enteric coronavirus, SARS-CoV-2 virus, hepatitis A virus, hepatitis B virus, hepatitis C virus, Japanese encephalitis virus, dengue virus, yellow fever virus, West Nile virus, Zika virus, rubella virus, measles virus, human RSV, rabies virus, Crimean Congo hemorrhagic fever virus, Ebola virus, Marburg virus, varicella-zoster virus, smallpox virus, human immunodeficiency virus, human T-cell leukemia virus, adenovirus, human papillomavirus, poliovirus, polyomavirus, norovirus, rotavirus, monkeypox virus, vaccinia virus, molluscipox virus, parapox virus, herpes virus, eastern and western equine encephalitis viruses, rhinovirus, foot-and-mouth disease virus, enterovirus, coxsackievirus, hepatovirus, astrovirus, sapovirus, hepatitis E virus, parainfluenza virus, mumps virus (epidemic parotitis), human metapneumovirus, Nipah virus, Hendra virus, onion yellow dwarf virus, Lassa virus, Funin virus, Machupo virus, Guanarito virus, Sabia virus, Sin Nombre hantavirus, Seoul virus, Epstein-Barr virus, cytomegalovirus, etc. Among them, preferably, influenza virus, SARS coronavirus, MERS coronavirus, human coronavirus, feline enteric coronavirus, SARS-CoV-2 virus, hepatitis A virus, hepatitis B virus, hepatitis C virus, human RSV, adenovirus, poliovirus, norovirus, rotavirus, rhinovirus, and enterovirus can be targeted for inactivation. Examples of bacteriophages, which are viruses that infect bacteria, include φX174 phage, M13 phage, MS2 phage, λ phage, T4 phage, and the like.

[0038] Examples of the dosage forms of the virus inactivator of the present invention include granules, powders, fine granules, liquid preparations, and the like. Among them, it is preferable to use solid forms such as granules, powders, and fine granules.

[0039] In order to granulate and dry the virus inactivator of the present invention, the following binders, excipients, etc. can be contained in the virus inactivator of the present invention. Thereby, the dosage form of the virus inactivator of the present invention can be made into granules, powders, fine granules, etc. When granulating the virus inactivator of the present invention, for example, if it is a granule, the particle size is preferably about 1 to 5 mm.

[0040] Examples of the binder used when granulating the virus inactivator of the present invention include celluloses such as carboxymethyl cellulose, hydroxymethyl cellulose, and hydroxypropyl methyl cellulose; starch-based substances such as starch and starch; natural polymer compounds such as gum arabic; and synthetic polymer compounds such as polyvinyl alcohol. One or more of these can be mentioned. These binders may be contained in an amount of 0.5 to 5% by mass based on the virus inactivator of the present invention.

[0041] Examples of excipients include minerals such as perlite, talc, diatomaceous earth, bentonite, and clay minerals; sugars such as sucrose and glucose; and sugar alcohols such as maltitol, sorbitol, and xylitol.

[0042] When the dosage form of the virus inactivator of the present invention is a liquid preparation, for example, it can be made into a liquid preparation by dissolving the above-mentioned powder preparation in a liquid carrier. Examples of the carrier used in preparing the liquid preparation include alcohols such as water, methyl alcohol, and ethyl alcohol; ketones such as acetone and methyl ethyl ketone; ethers such as tetrahydrofuran and dioxane; aliphatic hydrocarbons such as hexane, kerosene, paraffin, and petroleum benzine; aromatic hydrocarbons such as benzene and toluene; esters such as ethyl acetate; and halogenated hydrocarbons such as dichloroethane.

[0043] The virus inactivator of the present invention may further contain a disintegrant or the like as necessary. For example, when using disintegrants such as organic acid esters such as paraoxybenzoic acid ester, stearic acid ester, ethyl lactate, and chlorophenyl salicylate; and organic acids such as malic acid, fumaric acid, tartaric acid, adipic acid, and succinic acid, the disintegration of the preparation by heating can be promoted, and the volatilization of the virus inactivator of the present invention can be made smooth. If necessary, various surfactants, potency enhancers, dyes, etc. can also be contained.

[0044] The virus inactivation effect of the virus inactivator of the present invention can be evaluated by the inactivation rate. The inactivation rate is represented by the following formula (1). Details are determined by the method described in the examples below.

[0045]

Number

[0046] LRV: log reduction value, logarithm reduction value of virus infectivity titer PFU: plaque formation unit, plaque forming unit

[0047] When the inactivation rate is 70% or more, it can be evaluated that there is an inactivation effect, preferably 85% or more, more preferably 90% or more, and even more preferably 99% or more.

[0048] The present invention also provides a virus inactivation method using a decomposition product of azodicarbonamide as an active ingredient. In the virus inactivation method of the present invention, the virus inactivator of the present invention is heated at a heating temperature of 200°C or higher, preferably 200 - 700°C, more preferably 300 - 500°C, to generate a decomposition product of azodicarbonamide.

[0049] The heating means is not particularly limited as long as it can generate a decomposition product of azodicarbonamide. For example, there are means such as the method of directly igniting and heating the virus inactivator as described above, the method of heating by contacting a heat source such as a heater, and the method of heating using a heat source such as a heating agent. Among them, from the viewpoints of ease of handling and efficient volatility of the decomposition product of azodicarbonamide, the method of heating using a heat source such as a heating agent is preferred, and it is more preferred to use a self-heating system that generates heat using a self-heating substance and a liquid for self-heating reaction as the heat source for heating.

[0050] In the virus inactivation method of the present invention, the decomposition product of azodicarbonamide is volatilized as an active ingredient into a desired space, preferably a sealed space. However, in order to obtain the inactivation effect by the decomposition product of azodicarbonamide, it is preferred to heat azodicarbonamide in the range of 0.1 - 2 g for a space of 1 m 3 , more preferably in the range of 0.3 - 1.5 g for a space of 1 m 3 , and even more preferably in the range of 0.5 - 1 g for a space of 1 m 3 .

Example

[0051] Hereinafter, the present invention will be further described by way of examples and comparative examples, but the present invention is not limited to the following examples in any way.

[0052] <Test Example 1> Using a self-heating system, azodicarbonamide was heated, and the inactivation effect of the decomposition product of azodicarbonamide, which is the active ingredient, on bacteriophage was evaluated.

[0053] (Example 1) [Preparation of formulation] According to the formulation described in Table 1, each component was mixed, granulated, and dried to prepare a granular formulation. The particle size per granule of the formulation was about 3 mm, and the length was about 5 mm.

[0054]

Table 1

[0055] The following were used as active ingredients. Active ingredient: Azodicarbonamide (trade name: Uniform AZ Ultra #1067-1 (manufactured by Otsuka Chemical Co., Ltd.))

[0056] [Preparation of self-heating device] In order to heat the formulation by a water-releasing heating system, a self-heating device 1 as shown in Fig. 1 was prepared as follows. 65 g of calcium oxide was contained as a water-releasing heating substance 8 from the bottom to the side of a bottomed cylindrical outer container 2 with a diameter of 53 mm, a height of 63 mm, and a depth of 40 mm. The outer container 2 had a plurality of water-passing holes at the bottom, and the water-passing holes were blocked by a water-permeable non-woven fabric sheet 3. Further, the inside of the outer container 2 was partitioned into two spaces by a partitioning member 4. The partitioning member 4 was cylindrical and had a bottom that was substantially hollow hemispherical, and its side wall was arranged concentrically with the peripheral wall of the outer container 2. The water-releasing heating substance 8 was filled in the space formed by the peripheral wall of the outer container 2, the partitioning member 4, and the non-woven fabric sheet 3, and 3.9 g (3.8 g of azodicarbonamide) of the above-prepared formulation 7 was contained inside the partitioning member 4. Further, on the upper open surface of the outer container 2, a lid member 5 having 7 openings with an opening of 0.8 cm 2 was covered, and the openings of the lid member 5 were blocked by a heat-meltable resin film 6 having air holes to prepare the self-heating device of Example 1.

[0057] [Preparation of medium] <Medium A NA + 0.5% NaCl medium> To Difco Nutrient Agar (manufactured by Becton, Dickinson and Company), 0.5% by volume of the total prepared medium of NaCl (manufactured by Wako Pure Chemical Industries, Ltd.) was added, and it was autoclaved (121 °C, 20 minutes). 15 mL of the autoclaved medium was dispensed into each petri dish (deep sterilized petri dish φ90×20 mm, manufactured by Atech Co., Ltd.) to obtain Medium A. <Medium B NB + 0.5% NaCl Medium> To Difco Nutrient Broth (manufactured by Becton, Dickinson and Company), 0.5% by volume of the total prepared medium of NaCl (manufactured by Wako Pure Chemical Industries, Ltd.) was added, and 10 mL portions were dispensed into test tubes and autoclaved (121 °C, 20 minutes). The autoclaved product was designated as Medium B. <Medium C NB + 0.5% Agar + 0.5% NaCl Medium> To Difco Nutrient Broth (manufactured by Becton, Dickinson and Company), 0.5% by volume of the total prepared medium of Bacto Agar (manufactured by Becton, Dickinson and Company) and NaCl (manufactured by Wako Pure Chemical Industries, Ltd.) were added, and the autoclaved product (121 °C, 20 minutes) was designated as Medium C.

[0058] [Preparation of Test Phage Solution] <Preparation of Host Bacterial Solution> Escherichia coli NBRC 13898 was cultured with shaking at 37 °C (150 - 200 rpm, 18 hours) using the NB + 0.5% NaCl medium of Medium B to obtain a host bacterial solution. <Preparation of Test Phage Solution> 100 μL of the host bacterial solution prepared above (about 10 8~9 CFU / mL) and 100 μL of bacteriophage (E.coli phage Phi-X174 NBRC 103405) (about 10 5~6PFU / mL) was added and mixed, and the mixture was allowed to stand at 35°C for 10 - 20 minutes. After adding 4 mL of Medium C warmed to 45 - 50°C to the mixture and mixing, it was overlaid on Medium A and cultured at 35 ± 1°C for 18 ± 2 hours without inversion. After culturing, the upper layer was collected into a Stomacher bag (15 × 11 cm, manufactured by Atech Co., Ltd.) using a Conrage rod, crushed, and allowed to stand for 1 hour. This liquid was transferred to a centrifuge tube and centrifuged at 3500 rpm for 10 minutes, and the supernatant was transferred to another centrifuge tube. After repeating this centrifugation operation two more times, the supernatant was filtered through a membrane filter with a pore size of 0.22 μm to obtain a phage stock solution. The phage stock solution was diluted with a PBS solution (Phosphate Buffered Saline (PBS) Tablets, manufactured by Takara Bio Inc.) to prepare a solution with approximately 10 6 PFU / mL, which was used as the test phage solution.

[0059] [Preparation of test specimens] [Preparation of test specimen for hard surface with drying (FRP)] 100 μL of the test phage solution was divided into 20 drops and dropped onto a 5 × 5 cm FRP (fiber-reinforced plastic). Then the FRP was dried for about 30 minutes to obtain a test specimen for a hard surface with drying. [Preparation of test specimen for hard surface without drying (FRP)] 100 μL of the test phage solution was divided into 20 drops and dropped onto a 5 × 5 cm FRP (fiber-reinforced plastic) to obtain a test specimen for a hard surface without drying. [Preparation of test specimen for fiber (cotton cloth)] A 5 × 5 cm cotton cloth (Kanakin No. 3, conforming to JIS L 0803) was attached to the lid of a petri dish (deep sterilized petri dish φ90 mm × height 20 mm, manufactured by Atech Co., Ltd.). 100 μL of the test phage solution was dropped onto the center of the cotton cloth to obtain a test specimen for fiber. [Preparation of test specimen for hard surface with unevenness (ground glass)] 100 μL of the test phage solution was divided into 20 drops and dropped onto a 4.95 × 5 cm area of ground glass (parallel plate glass, 49.5 mm × 99.5 mm × thickness 1 mm, one-sided wire-edge chamfered). The test phage solution was spread over a 4.95 × 5 cm area using a Conrage rod to obtain a test specimen for a hard surface with unevenness.

[0060] [Test method] Approximately 3.8 m shown in Fig. 2 3 (1.2 m (vertical) × 1.6 m (horizontal) × 2 m (height) ≒ 3.8 m 3 ) At the center of the floor part 14 of the test chamber 11 (specimen installation part 12, the location indicated by the black triangle in Fig. 2), one self-heating device of Example 1 was installed. Then, the test pieces prepared above were installed at the ceiling part 13 of the test chamber 11 (directly above the specimen installation part 12) and at a location approximately 15 cm away from the specimen installation part 12 of the floor part 14, respectively (the locations indicated by black circles in Fig. 2). Note that, as a control (untreated), the above test pieces were left standing outside the test chamber 11. The temperature and humidity of the place where the test chamber 11 and the control (untreated) were left standing were set to approximately 25 °C and approximately 70%, respectively.

[0061] As shown in Fig. 1, the self-heating device 1 started a hydrolysis heating reaction by immersing it in a container 9 containing 22 mL of water as the hydrolysis heating reaction liquid W, and heated the preparation 7. After starting the heating, the ventilation fan of the test chamber 11 was stopped and the door was closed to make it in a non-ventilated state, and it was sealed for 1 hour.

[0062] Thereafter, when the test piece is FRP, the FRP was collected in a stomacher bag (15 × 11 cm, manufactured by Atech Co., Ltd.) containing 10 mL of SCDLP medium (Soybean-Casein Digest Broth with Lecithin & Polysorbate 80 “DAIGO”, manufactured by Nippon Pharmaceutical Co., Ltd.). The surface of the collected FRP was washed out while rubbing it from the outside of the stomacher bag. The washed-out SCDLP medium was used as the test stock solution, and the test stock solution was appropriately diluted using a PBS solution (Phosphate Buffered Saline (PBS) Tablets, manufactured by Takara Bio Inc.). When the test piece is cotton cloth, the cotton cloth peeled off from the lid of the petri dish is rolled up and placed in a Falcon tube (15 mL Centrifuge tube, manufactured by IWAKI) containing 7 mL of SCDLP medium. The SCDLP medium in the petri dish where the cotton cloth was attached was rinsed into the Falcon tube while washing the petri dish. The Falcon tube containing the cotton cloth was shaken by vortex and washed out. The washed-out liquid was used as the test stock solution and appropriately diluted using a PBS solution (Phosphate Buffered Saline (PBS) Tablets, manufactured by Takara Bio Inc.). When the test piece is ground glass, it was collected in a stomacher bag containing 10 mL of SCDLP medium. The surface of the collected ground glass was washed out while rubbing it from the outside of the stomacher bag. The washed-out SCDLP medium was used as the test stock solution, and the test stock solution was appropriately diluted using a PBS solution. 100 μL of the test stock solution or diluted solution was mixed with 100 μL of pre-cultured Escherichia coli and allowed to stand at 35°C for 20 minutes to obtain a mixed solution. After adding 4 mL of medium C warmed to 45 - 50°C to the mixed solution and mixing, it was overlaid on medium A and cultured at 35°C for 18 hours without inversion.

[0063] [Evaluation] The number of plaques (PFU) on the medium was counted, and the virus infectivity titer (PFU / test piece) for each of the ceiling and floor parts of the laboratory was calculated. Also, the inactivation rate (%) was calculated using the following formula (1).

[0064]

Number

[0065] LRV: log reduction value, logarithmic reduction value of virus infectivity titer PFU: plaque formation unit, plaque forming unit

[0066] The results are shown in Tables 2 to 5. The virus infection titer (PFU / specimen) in Tables 2 to 5 is the average value of the values calculated in the two tests conducted. Based on this average value, the inactivation rate (%) was calculated using the above formula (1).

[0067]

Table 2

[0068]

Table 3

[0069]

Table 4

[0070]

Table 5

[0071] As shown in Tables 2 to 5, when the virus inactivator of the present invention was volatilized by the hydrothermal heating system, a good virus inactivation effect was observed on both the ceiling and floor of the laboratory. In particular, a high virus inactivation effect was observed when the object was a fibrous or uneven hard surface.

[0072] <Test Example 2> Using a hydrothermal heating system, azodicarbonamide was heated, and the inactivation effect of the decomposition product of azodicarbonamide, which is the active ingredient, against the SARS-CoV-2 virus was evaluated.

[0073] (Example 2) [Formulation] The same formulation as the formulation prepared in Test Example 1 was used.

[0074] [Preparation of self-heating device] In the same manner as in Test Example 1, a self-heating device of Example 2 was fabricated. The amount of the preparation contained inside the partition member was 1.0 g (0.98 g of azodicarbonamide).

[0075] [Eluate] As the eluate, a solution obtained by diluting SCDLP 10-fold with DMEM (Dulbecco’s modified Eagle’s Medium (low-Glucose), manufactured by SIGMA, Cat#D6046) containing 2% FBS (Fetal Bovine Serum, manufactured by NICHIREI, Cat#174012) was used.

[0076] [Preparation of test virus solution] VeroE6 / TMPRSS2 JCRB1819, a host cell, was infected with SARS-CoV-2 (Severe acute respiratory Syndrome coronavirus2, NIID isolate; JPN / TY / WK-521). After culturing, the cell residue was removed by centrifugation to obtain a test virus solution (>10 8 PFU / mL).

[0077] [Preparation of test piece] [Preparation of fiber test piece (cotton cloth)] A 5×5 cm cotton cloth (Kanakin No. 3, compliant with JIS L 0803) was attached to the lid of a petri dish (deep sterilized petri dish φ90 mm × height 20 mm, manufactured by ATECT Co., Ltd.). 100 μL of the test virus solution was dropped onto the center of the cotton cloth to obtain a fiber test piece.

[0078] [Test method] As shown in Figure 3, 1 m 3 (1 m (vertical) × 1 m (horizontal) × 1 m (height) = 1 m 3) In the central part of the floor surface portion 24 of the sealed container 21 (the specimen installation portion 22, the location indicated by the black triangle in Fig. 3), one self-heating device of Example 2 was installed. Then, as shown in Fig. 3, the test pieces prepared above were installed at the central part of the ceiling portion 23 of the sealed container 21 and at positions approximately 10 cm away from the central part to the left and right (the locations indicated by the black circles in Fig. 3). And as a control (untreated), the above test pieces were left standing in another sealed container. Note that the sealed container in which the self-heating device was installed and the sealed container of the control (untreated) were left standing in a place with a temperature of about 25 °C and a humidity of about 75%.

[0079] As shown in Fig. 1, the self-heating device 1 was immersed in a container 9 containing 22 mL of water as the liquid W for the hydrolysis exothermic reaction to start the hydrolysis exothermic reaction and heat the preparation 7. After starting the heating, the sealed container was sealed and left in a non-ventilated state for 1 hour.

[0080] Thereafter, the test pieces were collected in a 50 mL Falcon tube, 10 mL of eluent was added, and they were eluted. The eluted liquid was used as the test stock solution and appropriately diluted using DMEM (Dulbecco’s modified Eagle’s Medium (low-Glucose), manufactured by SIGMA, Cat#D6046) containing 2% FBS (Fetal Bovine Serum, manufactured by NICHIREI, Cat#174012). The virus infectivity titer per 100 μL of the test stock solution or the diluted solution was measured by the plaque assay method.

[0081] [Evaluation] The number of plaques (PFU) on the culture medium was counted, and the virus infectivity titer (PFU / specimen) for each of the ceiling portion (center), ceiling portion (right side), and ceiling portion (left side) of the sealed container was calculated. Also, in the same manner as in Test Example 1, the inactivation rate (%) was calculated using Equation (1).

[0082] The results are shown in Table 6. Note that the virus infectivity titer (PFU / specimen) in Table 6 is the average value of the values calculated from the tests conducted at three points: the ceiling portion (center), ceiling portion (right side), and ceiling portion (left side). Based on this average value, the inactivation rate (%) was calculated using the above Equation (1).

[0083]

Table 6

[0084] As shown in Table 6, when the virus inactivator of the present invention was volatilized by a hydrothermal heating system, a good virus inactivating effect was observed on the test pieces installed on the ceiling of the sealed container even against the SARS-CoV-2 virus.

[0085] <Test Example 3> Using a hydrothermal heating system, azodicarbonamide was heated, and the inactivating effect of the decomposition product of azodicarbonamide, which is the active ingredient, against influenza virus was evaluated.

[0086] (Example 3) [Formulation] The same formulation as the one prepared in Test Example 1 was used.

[0087] [Preparation of self-heating device] In the same manner as in Test Example 1, the self-heating device of Example 3 was prepared. The amount of the formulation accommodated inside the partition member was 1.0 g (0.98 g of azodicarbonamide).

[0088] [Preparation of test virus solution] Host cells (MDCK cells ATCC CCL-34) were infected with influenza virus (Influenza A virus (H1N1): A / PR / 8 / 34; ATCC VR-1469). After culturing, the cell residue was removed by centrifugation, and the resulting solution was used as the test virus solution (>10 8 PFU / mL).

[0089] [Preparation of test piece] [Preparation of test piece with dry hard surface (FRP)] 100 μL of the test virus solution was divided into 20 drops and dropped onto a 5×5 cm FRP (fiber reinforced plastic). Then, the FRP was dried for about 30 minutes to obtain a test piece with a dry hard surface. <Preparation of Fiber Specimen (Cotton Cloth)> A 5×5 cm cotton cloth (Kanakin No. 3, compliant with JIS L 0803) was attached to the lid of a petri dish (deep sterilization petri dish φ90 mm × height 20 mm, manufactured by Atect Co., Ltd.). 100 μL of the test virus solution was dropped onto the center of the cotton cloth to obtain a fiber specimen.

[0090] [Test Method] As shown in Fig. 4, 1 m 3 (1 m (vertical) × 1 m (horizontal) × 1 m (height) = 1 m 3 ) of the central part of the floor surface 34 of the sealed container 31 (specimen installation part 32, the location indicated by the black triangle in Fig. 4), one self-heating device of Example 3 was installed. Then, as shown in Fig. 4, the specimens prepared above were installed on the ceiling part 33, the floor surface 34, and the wall surface 35 of the sealed container 31 (the locations indicated by black circles in Fig. 4). The installation of the specimen on the floor surface 34 was made at a location about 15 cm away from the specimen installation part 32, and the installations on the ceiling part 33 and the wall surface 35 were made at the central parts respectively. And as a control (untreated), the above specimen was left standing in another sealed container. The sealed container with the self-heating device installed and the sealed container of the control (untreated) were left standing in a place with a temperature of about 25°C and a humidity of about 75%.

[0091] As shown in Fig. 1, the self-heating device 1 started the hydrolysis heating reaction by immersing the container 9 containing 22 mL of water as the hydrolysis heating reaction liquid W, and heated the preparation 7. After starting the heating, the sealed container was sealed and left in a non-ventilated state for 1 hour.

[0092] After that, when the test piece is FRP, the FRP was collected into a stomacher bag (15×11 cm, manufactured by Atech Co., Ltd.) containing 10 mL of SCDLP medium (Soybean-Casein Digest Broth with Lecithin & Polysorbate 80 “DAIGO”, manufactured by Nippon Pharmaceutical Co., Ltd.). The surface of the collected FRP was washed out while rubbing it from the outside of the stomacher bag. The washed-out SCDLP medium was used as the test stock solution, and the test stock solution was appropriately diluted using EMEM (Minimum Essential Medium Eagle, manufactured by SIGMA, Cat#4655). Also, when the test piece is a cotton cloth, 10 mL of the washing solution was added to a 50 mL Falcon tube and washed out. The washed-out solution was used as the test stock solution and appropriately diluted using a cell culture solution (Minimum Essential Medium Eagle; EMEM, manufactured by SIGMA, Cat#M4655). The viral infectivity titer per 100 μL of the test stock solution or dilution was measured by the plaque assay method.

[0093] [Evaluation] The number of plaques (PFU) on the medium was counted, and the viral infectivity titer (PFU / test piece) for each of the ceiling, wall, and floor surfaces of the sealed container was calculated. Also, in the same manner as in Test Example 1, the inactivation rate (%) was calculated using Equation (1).

[0094] The results are shown in Tables 7 and 8. The viral infectivity titer (PFU / test piece) in Tables 7 to 8 is the average value of the values calculated in a total of three tests. Based on this average value, the inactivation rate (%) was calculated using the above Equation (1).

[0095]

Table 7

[0096]

Table 8

[0097] As shown in Tables 7 to 8, when the virus inactivator of the present invention was volatilized by a hydrothermal heating system, a good virus inactivating effect against influenza virus was observed on any of the ceiling, wall, and floor surfaces of the sealed container.

[0098] <Test Example 4> The inactivation effect of the decomposition product of azodicarbonamide, which is an active ingredient, against bacteriophage was evaluated by changing the size of the treatment space.

[0099] (Example 4) [Formulation] The same formulation as the formulation prepared in Test Example 1 was used.

[0100] [Preparation of self-heating device] In order to heat the formulation by a hydrothermal heating system, a self-heating device 1 as shown in FIG. 1 was prepared as follows. 76 g of calcium oxide was contained as a hydrothermal heating substance 8 from the bottom to the side of a bottomed cylindrical outer container 2 having a diameter of 60 mm, a height of 70 mm, and a depth of 45 mm. The outer container 2 had a plurality of water passage holes at the bottom, and the water passage holes were blocked by a water-permeable non-woven fabric sheet 3. Further, the inside of the outer container 2 was partitioned into two spaces by a partition member 4. The partition member 4 was cylindrical and had a bottom portion substantially in the shape of a hollow hemisphere, and its side wall was arranged concentrically with the peripheral wall of the outer container 2. The hydrothermal heating substance 8 was filled in the space formed by the peripheral wall of the outer container 2, the partition member 4, and the non-woven fabric sheet 3, and 11.7 g (11.5 g of azodicarbonamide) of the above-prepared formulation 7 was contained inside the partition member 4. Further, on the upper open surface of the outer container 2, a lid member 5 having nine openings with an area of 0.8 cm 2 was covered, and the openings of the lid member 5 were blocked by a heat-meltable resin film 6 having air holes to prepare a self-heating device of Example 4.

[0101] [Medium] The same media as Media A to Media C prepared in Test Example 1 were used.

[0102] [Test phage solution] A test phage solution similar to the test phage solution prepared in Test Example 1 was used.

[0103] [Preparation of Test Specimens] [Preparation of Fiber Test Specimens (Cotton Cloth)] A 5×5 cm cotton cloth (Kanakin No. 3, conforming to JIS L 0803) was affixed to the lid of a petri dish (deep sterilized petri dish φ90 mm × height 20 mm, manufactured by Atech Co., Ltd.). 100 μL of the test virus solution was dropped onto the center of the cotton cloth to obtain a fiber test specimen.

[0104] [Test Method] Approximately 15 m shown in Figure 5 3 (1.74 m (length) × 3.56 m (width) × 2.39 m (height) ≒ 15 m 3 ) or approximately 23 m 3 (2.66 m (length) × 3.60 m (width) × 2.39 m (height) ≒ 23 m 3 ) One self-heating device of Example 4 was installed at the center of the floor surface 44 of the test chamber 41 (specimen installation part 42, the location indicated by the black triangle in the figure below). Then, as shown in Figure 5, the test specimens prepared above were installed on the ceiling part 43, floor surface 44, and wall surface 45 of the test chamber 41 (the locations indicated by black circles a~f in Figure 5). The installation of the test specimen on the ceiling part 43 was at the center (directly above the specimen installation part 42, the location indicated by black circle a in Figure 5), the installation on the floor surface 44 was at a location approximately 15 cm away from the specimen installation part 42 (the location indicated by black circle b in Figure 5), the central part along the short side wall surface 45A and the central part along the long side wall surface 45B (the locations indicated by black circles c, d in Figure 5), and the installation on the wall surface 45 was at a height of 1 m from black circles c and d (the locations indicated by black circles e, f in Figure 5). And as a control (untreated), the above test specimens were left standing in a test chamber without specimen treatment. The temperature and humidity of the test chamber with the self-heating device of Example 4 installed and the control (untreated) test chamber were set to approximately 25°C and approximately 75%.

[0105] As shown in Figure 1, the self-heating device 1 initiated a hydrolysis heating reaction by immersing a container 9 containing 28 mL of water as the hydrolysis heating reaction solution W, and heated the preparation 7. After starting the heating, the ventilation fan in Laboratory 41 was stopped and the door was closed to create a non-ventilated state, and it was sealed for 1 hour.

[0106] After that, the cotton cloth peeled from the lid of the petri dish was rolled up and placed in a Falcon tube (15 mL Centrifuge tube, manufactured by IWAKI) containing 7 mL of SCDLP medium, and the SCDLP medium was recovered into the Falcon tube while washing the petri dish to which the cotton cloth was attached with 3 mL of SCDLP medium. The Falcon tube containing the cotton cloth was shaken by vortex and washed out. The washed-out liquid was used as the test stock solution and appropriately diluted using a PBS solution (Phosphate Buffered Saline (PBS) Tablets, manufactured by Takara Bio Inc.). 100 μL of the test stock solution or diluted solution was mixed with 100 μL of pre-cultured Escherichia coli and allowed to stand at 35°C for 20 minutes to obtain a mixed solution. After adding 4 mL of Medium C warmed to 45 - 50°C to the mixed solution and mixing, it was overlaid on Medium A and cultured at 35°C for 18 hours without inversion.

[0107] [Evaluation] The number of plaques (PFU) on the medium was counted, and the virus infection titer (PFU / specimen) for each of the ceiling, wall, and floor parts of the laboratory was calculated. Also, in the same manner as in Test Example 1, the inactivation rate (%) was calculated using Equation (1).

[0108] The results are shown in Tables 9 and 10. The virus infection titer (PFU / specimen) in Tables 9 - 10 is the average value of the values calculated in two tests. Based on this average value, the inactivation rate (%) was calculated using the above Equation (1).

[0109]

Table 9

[0110]

Table 10

[0111] As shown in Tables 9 to 10, when the virus inactivator of the present invention was volatilized by a hydrothermal heating system, in a space of about 15 m 3 and about 23 m 3 , a good virus inactivating effect was observed on any of the ceiling, wall, and floor surfaces of the laboratory.

[0112] From the above results, it was found that the decomposition product of azodicarbonamide generated by heating azodicarbonamide has a good virus inactivating effect under all conditions.

[0113] <Test Example 5> In this test, the self-heating device of Example 1 in Test Example 1 and the self-heating device of Example 4 in Test Example 4 were used. The self-heating device was heated, and the heating temperature of azodicarbonamide was measured by measuring the temperature every second. The times when the temperature reached 100 °C or higher, 150 °C or higher, 200 °C or higher, 250 °C or higher, 300 °C or higher, and 350 °C or higher were measured respectively. Also, the sum of the temperatures of 100 °C or higher, the sum of the temperatures of 150 °C or higher, the sum of the temperatures of 200 °C or higher, the sum of the temperatures of 250 °C or higher, the sum of the temperatures of 300 °C or higher, and the sum of the temperatures of 350 °C or higher were obtained respectively.

[0114] First, heat generation was started for the self-heating device (heat source) with the formulation removed from the self-heating device of Example 1 or Example 4, and the change in the heat generation temperature was measured respectively. Specifically, after removing the formulation 7 from the self-heating device 1 in Fig. 1, a temperature probe (K-type thermocouple (manufactured by Shin Nippon Kogyo Co., Ltd.: sheath thermocouple φ0.3 mm (MAX 600 °C))) was brought into contact with the center of the bottom X of the partition member 4. Since the temperature probe is linear, it was passed through the glass tube, the tip was bent, and the probe was pressed against the end of the glass tube to be in close contact with and fixed to the bottom of the can vertically. In this state, heat generation was started, and the heat generation temperature was measured and recorded over time every second using MT100 manufactured by Graph-Tech Co., Ltd. This test was conducted 3 times (specimens 1 to 3) in total. Next, based on the obtained temperature data, the times when the temperature reached 100°C or higher, 150°C or higher, 200°C or higher, 250°C or higher, 300°C or higher, and 350°C or higher were measured respectively. The results are shown in Tables 11 to 12. Also, the sum of the temperatures of 100°C or higher, the sum of the temperatures of 150°C or higher, the sum of the temperatures of 200°C or higher, the sum of the temperatures of 250°C or higher, the sum of the temperatures of 300°C or higher, and the sum of the temperatures of 350°C or higher were obtained respectively. The results are shown in Tables 13 to 14.

[0115]

Table 11

[0116]

Table 12

[0117]

Table 13

[0118]

Table 14

[0119] As can be seen from the results of Tables 11 to 12, the average time for the temperature to reach 100°C or higher was 900 seconds or more, the average time for the temperature to reach 150°C or higher was 450 seconds or more, the average time for the temperature to reach 200°C or higher was 350 seconds or more, the average time for the temperature to reach 250°C or higher was 250 seconds or more, the average time for the temperature to reach 300°C or higher was 200 seconds or more, and the average time for the temperature to reach 350°C or higher was 150 seconds or more. Also, as can be seen from the results in Tables 13 to 14, the total sum of temperatures of 100°C or higher is on average 170,000 °C·s or higher, the total sum of temperatures of 150°C or higher is on average 140,000 °C·s or higher, the total sum of temperatures of 200°C or higher is on average 120,000 °C·s or higher, the total sum of temperatures of 250°C or higher is on average 100,000 °C·s or higher, the total sum of temperatures of 300°C or higher is on average 80,000 °C·s or higher, and the total sum of temperatures of 350°C or higher is on average 60,000 °C·s or higher.

[0120] <Test Example 6> In the decomposition products of azodicarbonamide as the active ingredient, the virus inactivation effects of the floating substances were evaluated respectively.

[0121] [Formulation] The same formulation as the formulation prepared in Test Example 1 was used.

[0122] [Medium] The same media as Media A to Media C prepared in Test Example 1 were used.

[0123] [Test phage solution] The same test phage solution as the test phage solution prepared in Test Example 1 was used.

[0124] [Preparation of test pieces] <Preparation of test pieces of fiber (cotton cloth)> A 5×5 cm cotton cloth (Kanakin No. 3, conforming to JIS L 0803) was attached to the lid of a petri dish (deep sterilized petri dish φ90 mm × height 20 mm, manufactured by Atect Co., Ltd.). 100 μL of the test virus solution was dropped onto the center of the cotton cloth to obtain a test piece of fiber.

[0125] [Collection of floating substances of decomposition products of azodicarbonamide] The decomposition products of azodicarbonamide were collected by the following procedure. 1. The self-heating device of Example 1 prepared in Test Example 1 was placed in a 200 L Tedlar bag, and as shown in Fig. 1, it was immersed in a container 9 containing 22 mL of water as the liquid W for the exothermic reaction upon addition of water, thereby starting the exothermic reaction upon addition of water in the above Tedlar bag, heating the preparation, and generating smoke. 2. After starting the heating, at regular intervals (less than 5 minutes after the start of heating, 5 minutes later, 15 minutes later, 30 minutes later, 60 minutes later, 90 minutes later), while removing the solid components from the above Tedlar bag using a 0.22 μm PTFE filter (Millex-FG (registered trademark), MILLIPORE) made of PTFE, the gas was extracted with a glass syringe, and the suspended matter of the decomposition product of azodicarbonamide was collected. The collection of the suspended matter of the decomposition product of azodicarbonamide less than 5 minutes after the start of heating was performed after confirming the generation of smoke after starting the heating.

[0126] [Test method] The two test pieces prepared above were placed in a 2 L Tedlar bag, and the suspended matter of the decomposition product of azodicarbonamide collected at regular intervals was injected respectively. After injection, the test pieces were left standing in the Tedlar bag for 60 minutes. Thereafter, the cotton cloth peeled off from the lid of the petri dish was rolled up and placed in a Falcon tube (15 mL Centrifuge tube, manufactured by IWAKI) containing 7 mL of SCDLP medium, and the SCDLP medium was recovered in the Falcon tube while washing the petri dish with the cotton cloth attached with 3 mL of SCDLP medium. The Falcon tube containing the recovered cotton cloth was shaken by vortex and washed out. The washed-out liquid was used as the test stock solution and appropriately diluted using a PBS solution (Phosphate Buffered Saline (PBS) Tablets, manufactured by Takara Bio Inc.). 100 μL of the test stock solution or diluted solution was mixed with 100 μL of pre-cultured Escherichia coli, left standing at 35 °C for 20 minutes to obtain a mixed solution. 4 mL of medium C warmed to 45 - 50 °C was added to the mixed solution and mixed, then overlaid on medium A, and cultured at 35 °C for 18 hours without inversion.

[0127] [Evaluation] The number of plaques (PFU) on the medium was counted, and the viral infection titer (PFU / specimen) was calculated. Also, in the same manner as in Test Example 1, the inactivation rate (%) was calculated using Equation (1).

[0128] The suspension of the decomposition product of azodicarbonamide collected within less than 5 minutes after the start of heating had a high virus inactivation effect of 90% or more. And the virus inactivation effect of the suspension of the decomposition product of azodicarbonamide collected after 5 minutes was less than 80%. From the above results, it was found that the suspension of the decomposition product of azodicarbonamide contains a component that inactivates the virus, and it was suggested that the suspension generated within less than 5 minutes after the start of heating, that is, immediately after the start of heating, has the highest virus inactivation effect.

[0129] Although the present invention has been described in detail with reference to specific embodiments, it will be apparent to those skilled in the art that various changes and modifications can be made without departing from the spirit and scope of the present invention. This application is based on a Japanese patent application filed on July 22, 2020 (Japanese Patent Application No. 2020-137131), the content of which is incorporated herein by reference.

Explanation of Signs

[0130] 1 Self-heating device 2 Outer container 3 Non-woven fabric sheet 4 Partition member 5 Lid member 6 Heat-melt resin film 7 Preparation 8 Water-releasing heat-generating substance 9 Container 11,41 Laboratory 12,22,32,42 Specimen placement part 13,23,33,43 Ceiling part 14,24,34,44 Floor part 21,31 Sealed container 35,45 Wall part 45A Short-side wall part 45B Long-side wall part W Liquid for water-releasing heat-generating reaction X Bottom of partition member

Claims

A virus inactivator comprising a decomposition product of azodicarbonamide obtained by heating azodicarbonamide using a water-adding heating system, wherein the decomposition product generated within 30 minutes immediately after the start of heating of the azodicarbonamide is used as an active ingredient. A virus inactivation method using a decomposition product of azodicarbonamide generated within 30 minutes immediately after the start of heating of azodicarbonamide by heating azodicarbonamide using a water-adding heating system as an active ingredient. The virus inactivation method according to claim 2, wherein the azodicarbonamide is heated at a heating temperature of 200 °C or higher to generate a decomposition product of the azodicarbonamide.

4. The azodicarbonamide is heated in the range of 0.1 to 2 g with respect to a space of 1 m ３ The virus inactivation method according to claim 2 or 3.

Images