JP5670201B2 - Antiviral agent and antiviral composition against envelope virus belonging to influenza A virus genus - Google Patents

Description

  The present invention relates to human or livestock pathogenic viruses such as enveloped viruses (eg, human influenza virus, avian influenza virus, herpes simplex virus type 1, Newcastle disease virus, vesicular stomatitis virus, viral hemorrhagic septicemia virus, etc. Extract of plants belonging to the genus Oyster which contains tannins, which is highly effective against fish disease virus) and highly safe to human body, catechins, wattle tannins, pentagalloyl glucose, coffee tannins, pyrogallol, gallic acid, pentyl tannins The present invention relates to an antiviral agent as an active ingredient and the like, and an antiviral composition containing the antiviral agent and useful for disinfection of the virus and prevention of infection.

  In general, viral diseases are difficult to treat because antibiotics and the like are ineffective, and have become a major problem for animals such as humans and livestock. In recent years, the fact that SARS and avian influenza have become a hot topic is a new memory. Viral diseases are also a major problem in cultured fish, but there is no effective treatment, and vaccine prevention is the main countermeasure.

  By the way, “Shibutsu” obtained by fermenting an extract of persimmon fruit has long been used as a Chinese medicine for lowering blood pressure in China, and has been popular as a folk medicine in Japan. This astringent astringent is rich in tannins and is said to have astringency (a property that binds to proteins and the like to tighten the tissue), as well as antibacterial and deodorizing effects. Regarding the structure and purification method of tannin (condensed tannin) contained in oysters, the following two academic papers (Matsuo and Itoo, 1981a / 1981b: Non-patent documents 1 and 2) can be referred to.

  Examples of such a composition containing persimmon astringent or persimmon tannin include, for example, an antibacterial dental composition containing a persimmon astringent extract with cyclodextrin to further improve handling and antibacterial properties (special JP 2005-232043: Patent Document 1), anticancer agent and anti-pneumonia virus agent obtained by further adding a mixture of ingredients such as peptide polysaccharide contained in Ganoderma spore (Japanese Patent Laid-Open No. 2004-331641: Patent Document 2) Has been proposed.

  JP-A-2006-206558 (Patent Document 3) describes an antibacterial composition containing a tannin substance, a fatty acid ester, a chelating agent and the like ([Claim 1]), and the tannin substance. Examples thereof include tannic acid, pyrocatechin, gallic acid, persimmon tannin, tea tannin, pentaploid tannin and the like ([Claim 4]). However, the effectiveness of this antibacterial composition has only been demonstrated against Escherichia coli and Staphylococcus aureus when tannic acid is used ([Example]). There is no specific disclosure that it has significant antiviral properties against envelope viruses, and therefore is extremely useful as a component of antiviral compositions.

  JP-A-2006-306836 (Patent Document 4) describes that a specific phenol derivative is effective as an inactivating agent for various non-enveloped or enveloped viruses. As the phenol derivative, gallic acid alkyl ester, (N-propyl gallate, n-octyl gallate, catechin gallate, gallocatechin gallate, epicatechin gallate, etc.) are exemplified. However, in the Examples, although it has been specifically shown that n-octyl gallate has antiviral activity against herpes simplex virus type 1 (HSV-1) and vesicular stomatitis virus (VSV), Whether catechin gallate or the like contained has antiviral activity has not been demonstrated.

  Japanese Patent Application Publication No. 2004-529889 (Patent Document 5) discloses a C1-C3 alcohol (for example, ethanol) or a C2-C4 diol and an acid (a sufficient amount for adjusting the pH of the composition to 4.6 or less). For example, it is described that a composition containing an organic acid) has an inactivating action of envelope virus. However, the examples specifically show that a solution containing ethanol and hydrochloric acid, glycolic acid or succinic acid has antiviral activity against cold sores virus (HSV-1).

  The present inventors have heretofore used an antiviral agent against norovirus that causes food poisoning and infectious gastroenteritis using an oyster extract and an anti-norovirus composition using the same (PCT / JP2008 / 060705). And an antiviral agent against a non-enveloped virus using an oyster extract and other specific tannins or tannin-like substances and an antiviral composition (PCT / JP2009 / 056635) using the same. Sugiyama et al. (Non-patent Document 3) describe that persimmon astringent tannin exhibits a strong anti-norovirus action and the possibility of using it as a disinfectant (ethanol preparation).

JP 2005-232043 A JP 2004-331641 A JP 2006-206558 A JP 2006-306836 A Japanese translation of PCT publication No. 2004-529889

MATSUO, Tomoaki and ITOO, Saburo (1981a): Comparative Studies of Condensed Tannins from Several Young Fruits. J. Japan. Soc. Hort. Sci., 50 (2), 262-269. MATSUO, Tomoaki and ITOO, Saburo (1981b): A Simple and Rapid Purification Method of Condensed Tannins from Several Young Fruits.Agric.Biol.Chem., 45 (8), 1885-1887. Sugiyama, Hiroaki Nakai, Toru Toru, Satoshi Shimamoto, Examination of anti-norovirus action of plant-derived components and development of new ethanol preparations, Proceedings of the Annual Meeting of the Japanese Society of Food Microbiology, 2007, Vol.28th, p.56

  The present invention relates to an antiviral agent excellent in inactivating action of envelope virus and having high safety to the human body, and an antiviral composition containing this antiviral agent and useful for disinfection and prevention of infection of these viruses. The purpose is to provide.

  In order to solve the above problems, the present inventors have searched for substances and plant components that are recognized as foods or food additives, that is, substances that have antiviral activity from materials that are safe to use in the mouth. However, tannin-containing extracts of the genus Occumaceae have been found to have significant antiviral activity against a wide range of enveloped viruses, and other tannins or tannin-like substances, citric acid and / or salts thereof are also enveloped. The present invention has been completed by finding that it has antiviral activity against viruses.

The outline of the present invention is as follows.
[1] Depressing the enzyme derived from the plant belonging to the genus Diospyros contained in the squeezed or extracted liquid of the fruit of the genus Diospyros containing tannin by heating or treating with alcohol The antiviral agent with respect to envelope virus which uses the oyster extract processed material obtained by making it an active ingredient.
[2] The antiviral agent according to [1], wherein the processed product of oyster extract contains at least condensed tannin.
[3] The antiviral agent according to [1] or [2], wherein the plant belonging to the genus Oyster is Diospyros kaki.
[4] Further, catechins, wattle tannins, pentagalloyl glucose, coffee tannins, pyrogallol, gallic acid, pentaploid tannins, and organic acids and / or salts thereof (except those in the processed oyster extract) The antiviral agent according to any one of [1] to [3], which contains at least one selected from the group consisting of as active ingredients.
[5] The envelope virus according to [1] to [4], wherein the envelope virus belongs to an influenza virus genus, vesiculovirus genus, simple virus genus, abular virus genus, or nobirabrado genus. The antiviral agent in any one.
[6] The envelope virus is a human influenza virus, avian influenza virus, vesicular stomatitis virus, herpes simplex virus type 1, Newcastle disease virus, or viral hemorrhagic sepsis virus, according to [5] Antiviral agent.
[7] An antiviral alcohol preparation containing at least the antiviral agent according to any one of [1] to [6] and an alcohol.
[8] An antiviral cleaning composition comprising at least the antiviral agent according to any one of [1] to [6] and a surfactant.
[9] An antiviral disinfecting composition containing at least the antiviral agent according to any one of [1] to [6] and an antibacterial agent (excluding ethanol, organic acids and salts thereof).
[10] In any one of [7] to [9], the processed oyster extract (converted to solid content) in the antiviral agent is contained in a proportion of 0.01 to 5% by weight with respect to the entire composition. The antiviral composition as described.
[11] The antiviral composition according to any one of [7] to [10], which contains an organic acid and / or a salt thereof in such an amount that the pH of the composition is 6.0 to 2.0.
[12] The antiviral composition according to any one of [7] to [11], further containing vitamin Cs.

  As the oyster extract constituting the antiviral agent of the present invention, the squeezed or extracted liquid of the fruit of the genus Oyster plant is heated or treated with alcohol to thereby contain the plant of the genus Oyster What is obtained by inactivating the enzyme derived from the above (treated product of oyster extract) is preferable, and one containing at least condensed tannin, for example, one obtained from Diospyros kaki is preferable.

  The antiviral agent of the present invention includes oyster extracts, catechins (catechin, epicatechin, epigallocatechin, epicatechin gallate, epigallocatechin gallate, etc.), wattle, depending on the target envelope virus. Tannin, pentagalloylglucose, coffee tannin, pyrogallol, gallic acid, pentaploid tannin and the like can also be used as active ingredients. Furthermore, an organic acid and / or a salt thereof (excluding those in the oyster extract or a processed product thereof) can also be used as an active ingredient of an antiviral agent. These active ingredients of the antiviral agent may be used singly or in combination.

  Such an antiviral agent is an active ingredient against an envelope virus of a composition in combination with an alcohol, a surfactant, an antibacterial agent (excluding ethanol, organic acids and salts thereof), a moisturizing agent, cosmetic oils and the like. It is preferred to use.

  That is, the antiviral composition of the present invention contains the antiviral agent and at least one selected from the group consisting of alcohols, surfactants, antibacterial agents, moisturizers and cosmetic oils and fats. Features. Such an antiviral composition preferably contains the antiviral agent (in terms of solid content) in a proportion of 0.01 to 5% by weight based on the entire composition. It is also preferable to contain an organic acid and / or a salt thereof in such an amount that the pH of the composition is 6.0 to 2.0. Further, the antiviral composition preferably contains vitamin Cs.

  For example, the antiviral composition of the present invention comprises an antiviral alcohol preparation containing at least the antiviral agent and an alcohol, an antiviral cleaning composition containing at least the antiviral agent and a surfactant, It is provided as an antiviral disinfecting composition containing the antiviral agent and the antibacterial agent.

  In other words, the present invention relates to an envelope virus, such as spraying, applying, etc., to an area where there is a possibility of contamination by the envelope virus, such as an antiviral agent or antiviral composition that is a substance containing the above-described components. Provide a method for use in disinfecting or preventing infection.

  Furthermore, the antiviral agent of the present invention can also be used as an active ingredient of a therapeutic or prophylactic agent for infectious diseases caused by enveloped viruses. That is, the therapeutic or preventive agent for infectious diseases against the envelope virus of the present invention is characterized by containing the antiviral agent as an active ingredient.

  The effect of oyster extract, catechins, wattle tannin, pentagalloyl glucose, coffee tannin, pyrogallol, gallic acid, pentotannin, or organic acid and / or salt thereof used as an antiviral agent of the present invention on envelope viruses is It is remarkably superior to general antibacterial agents and the like, and 99% or more of these viruses can be eliminated. Usually, viruses have different structures depending on their types, so the behavior or resistance to chemical substances and chemicals is different for each type, but it is particularly useful for antiviral agents that use at least oyster extract. In that case, it has a feature that it is effective against a wide range of viruses regardless of the type of the virus. Such antiviral agents are not only substances that can be used alone, but also compositions such as alcohol preparations, cleaning compositions, hand soaps, disinfecting compositions, lotions, emulsions, creams, etc. Alternatively, it is extremely useful as an active ingredient such as pharmaceuticals against enveloped viruses. Then, the antiviral agent of the present invention or a composition containing the antiviral agent of the present invention is attached to the target envelope virus or a place where it may be attached (generally, a non-living body and a living body surface). However, when the composition is a pharmaceutical, it may be in the body of a living body) and used for disinfection or infection prevention.

  Since oyster extract (oyster tannin) and the like are recognized as food additives, all the components of the antiviral composition of the present invention are composed of food or food additives and adhere to food and tableware. It is possible to obtain a composition that does not cause a problem even if it is consumed. By using the antiviral composition of the present invention containing such an oyster extract as an active ingredient, it is possible to efficiently disinfect envelope viruses and prevent infection in situations where food is handled or in medical institutions. It is expected that the occurrence of diseases caused by these viruses can be greatly suppressed.

FIG. 1 shows the antiviral activity of various drugs against human influenza virus in Example 1. FIG. 2 shows the antiviral activity of various drugs against the avian influenza virus in Example 1. FIG. 3 shows the antiviral activity of various drugs against vesicular stomatitis virus in Example 1. FIG. 4 shows the antiviral activity of various drugs against herpes simplex virus type 1 in Example 1. FIG. 5 shows the antiviral activity of various drugs against Newcastle disease virus in Example 1. FIG. 6 shows the antiviral activity of various drugs against avian influenza virus in Example 4. FIG. 7 shows the antiviral activity of various drugs against human influenza virus in Example 5.

− Envelope virus −
The antiviral agent and antiviral composition of the present invention can be applied to a wide range of enveloped viruses. For example, the present invention can be applied to various enveloped viruses shown in Table 1, which are known as pathogenic viruses of humans or livestock (mammals and birds).

Moreover, as a fish disease virus, it can apply to the following various envelope viruses, for example.
(1) Rhabdoviridae, single-stranded RNA virus, cannonball type Novirhabdoviridae
Viral hemorrhagic septicemia virus (Viral hemorrhagic septicemia virus) ... Causes viral hemorrhagic sepsis mainly in salmonids in freshwater fish and flounder in marine fish.
(2) Herpesviridae, double-stranded DNA virus, spherical Ictalurivirus
American catfish herpesvirus (Ictalurid herpesvirus 1) ... causative agent of American catfish virus disease / Koi herpesvirus (genus unknown, unclassified) ... causative agent of koi herpesvirus disease. Viruses that have become very problematic in recent years.
(3) Reoviridae, double-stranded RNA virus, spherical aquareovirus genus (Aquareovirus)
Species unknown ... Goldfish capsized disease.
(4) Nimaviridae, double-stranded DNA virus, long spherical whispovirus genus (Whispovirus)
White spot syndrome virus ... The cause of white spot syndrome in shrimps.
(5) Roniviridae, single-stranded DNA virus, long spherical Okavirus
Yellow head virus ... The causative agent of shrimp yellow head disease.
(6) Baculoviridae, double-stranded DNA virus, amorphous.

Nucleopolyhedrovirus (Nucleopolyhedrovirus)
Monodon-type baculovirus (Penaeus monodon NPV): Cause of monodon-type baculovirus infection.

− Antiviral agent −
The active ingredient of the antiviral agent of the present invention is selected from among oyster extracts, catechins, wattle tannins, pentagalloyl glucose, coffee tannins, pyrogallol, gallic acid, pentaploid tannins, etc., depending on the target envelope virus. Appropriate ones can be selected.

-Oyster extract In the present invention, as an active ingredient of an antiviral agent against a wide range of enveloped viruses, an extract of an oyster genus plant containing tannin, that is, an oyster extract (sometimes referred to as persimmon shibutannin) is used. . In addition, this oyster extract may contain the solvent etc. which were used for extracting not only the substance derived from the plant of the genus Oyster which contains tannin.

  The raw material of the oyster extract is not particularly limited, but it is efficient to use immature fruits of astringents (for example, oyster oysters, varieties such as flat seedless) that are rich in oyster tannins (especially condensed tannins) And economical. Moreover, as long as the oyster extract which consists of a similar component is obtained, it is good also considering a site | parts other than fruits, such as a leaf and a bark of a plant of the genus Oyster.

  A method for preparing an oyster extract from such a raw material is not particularly limited, but generally, a method for recovering squeezed juice by pulverizing and compressing an astringent from which cocoons have been removed, or an appropriate size. For example, a method in which the mixture is cut into a liquid and then liquefied by a mixer, and the supernatant is collected by a centrifuge, or a method in which the extract is collected by extraction with water or an aqueous solvent is used.

-Heating, alcohol and other treatments As the oyster extract of the present invention, squeezed juice or extract of the fruits of the genus Oyster can be used as they are, but those heated or treated with alcohol ( Hereinafter, it is desirable to use “processed oyster extract”. The antiviral properties of the oyster extract are further increased by heating or alcohol treatment, and at the same time, the measurement for verifying the antiviral properties can be prevented from being inhibited. Such a processed product of oyster extract can be prepared relatively easily and has the advantage that color and odor are hardly a problem when used as a component of the composition, and it takes time for fermentation. It is easier to use industrially than amber (see below), which is difficult to use in terms of color and odor. Further, even when stored for a long time by heating or alcohol treatment as described above, no discoloration or precipitation occurs.

  The temperature and time conditions of the heat treatment may be any conditions that can inactivate enzymes derived from plants belonging to the genus Oyster that are contained in juices, etc., and are generally used to deactivate plant enzymes. Conditions can be adopted. That is, the temperature is usually 60 to 130 ° C., and the time is usually 5 seconds to 30 minutes. For example, the heat treatment is performed at 120 ° C. to 130 ° C. for 5 to 10 seconds, or at about 85 ° C. for 5 to 15 minutes. Just do it. Moreover, the aspect of a heat processing process is not specifically limited, For example, the heating in the process which sterilizes juice, the heating in the process which pulverizes, or before the fermentation start for manufacturing a persimmon astringent (details are mentioned later) The treatment can be performed by heating or the like.

  On the other hand, the alcohol treatment can be usually performed using 30 to 100%, preferably 50 to 100% alcohol such as ethanol. For example, it is preferable to treat the oyster juice so as to add approximately the same amount of 95 v / v% ethanol, and then store it in a sealed light-shielding container (usually a light brown solution). Also, the aspect of the alcohol treatment step is not particularly limited. For example, the extraction step using an alcohol-based solvent such as ethanol corresponds to the alcohol treatment step, and typically, the antiviral use of the present invention. As one step for producing an alcohol preparation as a composition, alcohol can be added to the oyster extract that has been subjected to the above heat treatment, if necessary, and mixed. Such alcohol treatment also has an effect of sterilizing miscellaneous bacteria contained in the oyster extract itself.

  The oyster extract of the present invention is solidified by concentration, drying, or freeze-drying as necessary, in addition to the above-mentioned treatment, or in addition to the above-mentioned treatment, as long as the effects of the invention are not impaired. In addition, pulverization (freeze-dried powder is usually slightly yellow) or purification using an ion exchange resin or the like may be performed. The oyster extract contains a large amount of polyphenol, and if it remains in a liquid state, it tends to undergo coloration and other alterations. Therefore, it is desirable that the oyster extract be stored frozen in a solid state using a freeze-drying method. These operations are preferably performed under mild conditions such that oyster tannin and other components contained in the oyster extract are not decomposed.

  In addition, the oyster extract in the present invention is a liquid obtained by squeezing immature astringency and then fermenting and aging for a long period (about 1 to 3 years), and has a solid content of about several percent (oyster tannin) ) And organic acid produced by fermentation or the like may be used. Conventionally, this persimmon has been used as a folk medicine or paint, and is generally marketed as a product such as “Tsubaki Shibu” (Takeyama Shibu Production Center). Alternatively, it is also possible to use a fermentation product obtained by adding oyster-derived yeast culture solution to oyster juice and fermenting at 20 to 25 ° C. for 1 to 3 months (usually a reddish brown solution), and then a sealed container It is preferable to store within.

  It should be noted that the “List of Existing Additives Listed Items” in accordance with the Japanese Food Sanitation Law includes “柿 tannin” (product name / alias = 柿 shibu, 柿 extract. Basic, manufacturing method, essence = oyster oyster Diospyros kaki THUNB. The additive described as squeezed or obtained by extraction with water or ethanol. The main components are tannin and tannic acid.) The additive described as oyster extract in the present invention is used. You can also

-Oyster Tannins Plants of the genus Diospyros, especially their fruits, are generically called so-called tannins, which have certain properties, such as astringency and binding to metal ions, that make them feel astringent. Rich in compounds. Such oyster tannins often contain “oyster condensed tannin” represented by the following estimated structural formula (I), which is formed by binding catechin, gallocatechin and gallate esters thereof as a main component. It is characteristic that it is. For example, among the plants belonging to the genus Oyster, oyster-condensed tannins contained in the fruit of Diospyros kaki, native to Japan and widely cultivated worldwide, are catechin, catechin gallate, gallocatechin and gallocatechin. It is a polymer compound in which gallate is condensed with a carbon-carbon bond in a ratio of about 1: 1: 2: 2 (see Matsuo & Itoo (1981a): Non-patent Document 1 above).

  Further, oyster tannins may contain other tannic compounds such as catechins and hydrolyzable tannins in addition to the above “oyster condensed tannins”.

  Hydrolyzed tannin is an ester of an alcohol (such as glucose) and a carboxylic acid (such as gallic acid) or an oligomer thereof, and its molecular weight is reduced by hydrolysis, whereas oyster condensed tannin is hydrolyzed. It can be distinguished from hydrolyzed tannins because it does not reduce the molecular weight (the carbon-carbon bond of the basic skeleton of the polymer is not hydrolyzed). For example, it is described in Matsuo & Itoo (1981b) (Non-patent Document 2). It is also possible to purify and quantify by a method that has been developed.

  For antiviral expression against the enveloped virus in the present invention, it is presumed that at least oyster condensed tannin is contained in the oyster extract, but the contribution of other components in the oyster extract The possibility of is not excluded at all. The oyster extract obtained by the preparation method as described later using oyster fruit usually contains oyster condensed tannin, and the antiviral agent of the present invention uses such an oyster extract. It is presumed that it is preferable to use it as a raw material.

-Catechins The antiviral agent of the present invention includes influenza A virus genus (human influenza virus, avian influenza virus, etc.), vesiculovirus genus (vesicular stomatitis virus, etc.), simple virus genus (herpes simplex virus type 1) Etc.), catechins can also be used as active ingredients when targeting envelope viruses such as the genus Aburavirus (Newcastle disease virus etc.), Nobilabd virus genus (virus hemorrhagic sepsis virus etc.).

  Catechins are shrubs of Indian leguminous acacia genus, which are contained in plants such as catechu (also called gan beer; scientific name: Acacia catechu) and tea tree (tea tree, scientific name: Camellia sinensis). 7,3 ′, 4′-pentahydroxyflavan (catechin in the narrow sense), 3,5,7,3 ′, 4 ′, 5′-hexahydroxyflavan (gallocatechin) and their 3-galloyl derivatives, These stereoisomers are also included. For example, (+)-catechin separated from catechu has the following structural formula (2).

  In addition, catechins (sometimes referred to as “green tea tannins”) contained in tea tree are epicatechin [epicatechin, structural formula (3)] and epigallocatechin of its hydroxy form [epigallocatechin, structural formula (4) )], And their gallic acid esters epicatechin gallate [epicatechin gallate, structural formula (5)] and epigallocatechin gallate [epigallocatechin gallate, structural formula (6)] as main components, these compounds are heated. It may be isomerized by treatment.

  Catechins are also contained in other plants. In the present invention, these compounds may be isolated and used from a plant containing catechins, or an extract of a plant containing catechins may be used. Moreover, any one catechin may be used alone, or two or more catechins may be used in combination. It is most convenient to use catechins contained in chanoki.

-Watrutannin The antiviral agent of the present invention includes influenza A virus genus (human influenza virus, avian influenza virus, etc.), becyclovirus genus (vesicular stomatitis virus, etc.), simple virus genus (herpes simplex virus 1) Type), Avuravirus genus (Newcastle disease virus, etc.), Nobilabd virus genus (viral hemorrhagic septic virus, etc.), etc., it is also possible to use Watrutannin as an active ingredient it can.

  Watrutannin is a tannin extracted from the bark, leaves, and cocoons of plants of the genus Acacia. For example, Acacia pycnantha (Golden Wattle), Acacia decurrens (Tan Wattle), Acacia dealbata (Silver Wattle) And Acacia mearnsii (Black Wattle).

-Pentagalloyl glucose The antiviral agent of the present invention includes influenza A virus genus (human influenza virus, avian influenza virus, etc.), simple virus genus (herpes simplex virus type 1 etc.), abular virus genus (Newcastle disease) In the case of targeting envelope viruses such as viruses and the like, and nobirabradoviruses (such as viral hemorrhagic septic virus), pentagalloylglucose can also be used as an active ingredient.

  Pentagalloyl glucose is a compound in which gallic acid is ester-bonded to hydroxyl groups (1, 2, 3, 4 and 6 positions) of glucose, and can be obtained, for example, by decomposing and purifying pentaploid tannin as a raw material.

-Coffee tannin When the antiviral agent of the present invention targets an envelope virus such as Nobilabdovirus genus (such as viral hemorrhagic septic virus), coffee tannin can also be used as an active ingredient.

  Coffee tannins are tannins (or tannin-like substances) extracted from coffee beans, etc., and mainly caffeic acid esterified with chlorogenic acids (hydroxyl groups of quinic acid (any one or more of the 3, 4 or 5 positions)). Compound).

・ Pyrogallol Antiviral agent of the present invention includes influenza A virus genus (human influenza virus, avian influenza virus, etc.), becyclovirus genus (vesicular stomatitis virus, etc.), simple virus genus (herpes simplex virus type 1 etc.) In the case of targeting envelope viruses such as Nobirabridovirus (such as viral hemorrhagic sepsis virus), pyrogallol (1,2,3-trihydroxybenzene) can also be used as an active ingredient.

-Gallic acid In the case where the antiviral agent of the present invention targets an envelope virus such as Nobirabridovirus (viral hemorrhagic sepsis virus, etc.), gallic acid can also be used as an active ingredient.

-Ploidy tannin When the antiviral agent of the present invention targets an envelope virus such as Nobilabdovirus genus (viral hemorrhagic septic virus, etc.), the active ingredient is pentaploid tannin, which is derived from a quintuplet (nulde bug hump). Can also be used.

-Organic acid and / or salt thereof The antiviral agent of the present invention is an influenza A virus genus (human influenza virus, avian influenza virus, etc.), vesiculovirus genus (vesicular stomatitis virus, etc.), simple virus genus ( When targeting envelope viruses such as herpes simplex virus type 1), novirabdovirus (virus hemorrhagic septic virus, etc.), organic acids and / or salts other than those contained in oyster extracts It can also be used as an active ingredient.

  Organic acids and / or their salts are excellent in antibacterial properties against bacteria and are also recognized as food additives. In addition to increasing the solubility of tannin, coloring when tannin comes into contact with iron Also acts as a chelating agent to prevent From such a viewpoint, it is also preferable to add an organic acid and / or a salt thereof to the antiviral composition of the present invention.

  The organic acid and / or salt thereof is preferably an organic acid having 2 to 10 carbon atoms and / or a salt thereof, more preferably an organic acid containing a hydroxyl group having 2 to 10 carbon atoms and / or a salt thereof. More specifically, at least one organic acid selected from the group consisting of lactic acid, malic acid, citric acid, tartaric acid, salicylic acid, succinic acid, fumaric acid and itaconic acid and / or a salt thereof is preferable. Or its salt is preferable. Moreover, as a salt of an organic acid, the sodium salt of the said organic acid, potassium salt, etc. are preferable.

  When an organic acid and / or a salt thereof is added to the antiviral composition of the present invention as an active ingredient for a specific envelope virus and / or for other purposes as described above, the organic acid and / or its The proportion of the salt is preferably 0.05 to 5.0% by weight, more preferably 0.1 to 2.0% by weight, based on the whole antiviral composition (including the solvent and the like). Alternatively, the pH of the antiviral composition is usually 6.0 to 2.0, preferably 5.0 to 2.0, and more preferably 4.8 to 2.0. And more preferably in an amount of 4.0 to 2.0. The pH of the aqueous solution may be measured using a general pH meter (for example, a pH meter manufactured by Beckman Coulter, Inc.).

  In addition, when an antiviral agent containing an organic acid and / or a salt thereof as an active ingredient is used alone, it is preferable to adjust the pH of the antiviral agent itself within the above range, but the antiviral agent is an antiviral composition. In the case of using (diluted), the pH of the antiviral agent itself is adjusted in advance to be lower than the above range as necessary so that the final pH of the composition falls within the above preferable range. You may keep it.

− Antiviral composition −
The antiviral composition of the present invention contains an antiviral agent as an active ingredient against an enveloped virus, and at least one component of alcohol, surfactant, antibacterial agent, moisturizing agent, and cosmetic oils and fats. If necessary, the composition further contains citric acid and / or a salt thereof and vitamin C. Although the aspect is not specifically limited, The following are mentioned typically.

-Alcohol preparation containing at least antiviral agent and alcohol-Cleaning composition containing at least antiviral agent and surfactant-Disinfecting composition containing at least antiviral agent and antibacterial agent-At least antiviral Lotions, emulsions or creams containing humectants and moisturizers and / or cosmetic oils, including food, tableware, cooking utensils, fish, and other breeding equipment, breeding aquariums, workers' hands and clothes, etc. The composition of the aspect which can disinfect the virus and disinfect the envelope virus is provided as a liquid or solid detergent, for example. Alcohol preparations and disinfecting compositions are free of enveloped viruses and bacteria adhering to food, tableware, cooking utensils, fish and other breeding equipment, fish tanks, workers' hands, or patients handling filth. The composition of the embodiment used to activate, for example, provided as a propellant similar to conventional ethanol formulations. These cleaning compositions or disinfecting compositions can also be in a mode for disinfecting viruses such as fish, eggs, larvae or parent fish. Lotions, creams and milky lotions are compositions (basic cosmetics) that can be applied to the fingers of workers who are easily roughened by water work to provide skin care and disinfect envelope viruses.

  In the antiviral composition of the present invention, the alcohol, surfactant, antibacterial agent, humectant, and cosmetic fats and oils may naturally be used in combination of two or more. For example, for an alcohol preparation, it is also preferable to further add a surfactant such as a fatty acid ester in order to further improve antibacterial properties. Further, the cleaning composition can take a form such as a hand soap containing an antibacterial agent or an alcohol in addition to a surfactant, and the cream keeps the hand skin clean with components for protecting the hand skin. Therefore, it is possible to take an aspect in which an antibacterial agent or alcohol is added.

  In addition to the components specifically described herein, the antiviral composition of the present invention may be provided with various components, such as an increase in a desired performance and a quality of each composition. In a cosmetic such as a viscous agent (xanthan gum, locust bean gum, sodium polyacrylate, etc.), an antioxidant, a fragrance, a pigment, or a lotion, a rough skin preventing agent, an anti-inflammatory agent, and the like can be appropriately blended.

-Content of antiviral agent The content of the antiviral agent in the antiviral composition of the present invention depends on the compositional composition, usage method, etc., as long as antiviral properties against the envelope virus are expressed. The antiviral agent, more specifically, the active ingredient such as oyster extract in the antiviral agent is preferably 0.01 to 5% by weight with respect to the whole antiviral composition. More preferably, the amount may be 0.1 to 2% by weight.

  The content of the above-mentioned antiviral agent is based on the “solid content”. When a liquid material such as an extract of persimmon fruit is used as a production raw material, the solid content (dried in the liquid material) Alternatively, the blending amount of the liquid material may be adjusted so that the weight of the powder obtained by freeze-drying is within the above range. The squeezed coconut juice usually contains about 5 to 10% solid content.

-Vitamin C It is preferable to mix | blend vitamin C known as antioxidant added to food etc. with the antiviral agent of this invention in addition to the antiviral agent mentioned above. Here, “vitamin Cs” is a general term including DL-ascorbic acid, ascorbic acid ester (such as palmitic acid ester) and the like in addition to L-ascorbic acid generally called vitamin C. By adding vitamin C, the oxidation of oyster extract (especially oyster tannin) is suppressed, and the effect on the virus will be exerted stably and continuously. You can also.

  The amount of vitamin C added is preferably 0.01 to 5.0% by weight, preferably 0.05 to 2.0% by weight, based on the whole antiviral composition (including solvent and the like). Is more preferable.

-Alcohol As alcohol, the same alcohol as that used in general alcohol preparations can be used, but ethanol and / or propanol which have excellent antibacterial properties against bacteria and are recognized as food additives are preferable. The concentration of these alcohols may be about the same as that of a general alcohol preparation and can be adjusted in consideration of antibacterial properties, but is preferably about 10 to 80% with respect to the whole alcohol preparation. Alcohol may be used as a solvent in a composition other than an alcohol preparation, and may be blended in cosmetics or the like as a component that provides astringency and antiseptic properties to the skin.

・ Surfactant Surfactants include cationic, anionic, zwitterionic and nonionic surfactants. In view of chemical properties such as oyster condensed tannin (polyphenol), the present invention uses anionic surfactants. It is preferable to use a surfactant and / or a nonionic surfactant.

  Examples of the anionic surfactant include soap (alkali salt of higher fatty acid), monoalkyl sulfate, alkyl polyoxyethylene sulfate, alkyl benzene sulfonate, monoalkyl phosphate, and the like.

  Examples of the nonionic surfactant include polyoxyethylene alkyl ether, polyoxyethylene fatty acid ester, fatty acid partial ester of polyhydric alcohol (glycerin, sugar alcohol, etc.), fatty acid diethanolamide and the like.

  Among these surfactants, those recognized as food additives such as glycerin fatty acid partial ester, sorbitan fatty acid partial ester, and sucrose fatty acid partial ester do not pose a problem even if they adhere to food, tableware or cooking utensils. Therefore, it is a preferable surfactant in the present invention.

  The surfactants described above also have an action of destroying bacterial cell membranes and viral envelopes. For example, partial esters of glycerin with fatty acids having 6 to 18 carbon atoms (capric acid having 10 carbon atoms, etc.) Because of its excellent antiviral properties against enveloped viruses and antibacterial properties against Escherichia coli and Staphylococcus aureus, it is also suitable to incorporate these surfactants as active ingredients in the aforementioned antiviral agents or in compositions such as alcohol preparations. It is. The surfactant is also used as a component for mixing the oil phase and the aqueous phase in creams and emulsions.

Antibacterial agents Antibacterial agents (including substances called bactericides and disinfectants) other than the aforementioned organic acids such as ethanol and citric acid and salts thereof that can be used in the present invention are not particularly limited. Not known, but effective against known antibiotics and synthetic antibacterial agents such as Escherichia coli, Staphylococcus aureus, MRSA, Salmonella, Vibrio parahaemolyticus, Pseudomonas aeruginosa, etc. Those are preferred. Among them, synthetic antibacterial agents such as isopropylmethylphenol, butyl parahydroxybenzoate, and triclosan are preferable antibacterial agents in the present invention in terms of excellent antibacterial action and compatibility with oyster extract. In addition, the substance used as an antibacterial agent as described above may be blended in the ethanol preparation described above, and may be used as a preservative in cosmetics and the like.

-Moisturizer The moisturizer (humectant) that can be used in the present invention is the same as that used in cosmetics such as general lotions, emulsions, creams, etc., for example, glycerin, propylene glycol, sorbitol, polyethylene Examples include glycol, hyaluronic acid, sodium chondroitin sulfate, ceramide, and aloe extract. Among these humectants, those recognized as foods or food additives such as aloe extract are preferred humectants in the present invention in that they do not pose a problem even if they adhere to foods, tableware, and cooking utensils.

・ Cosmetic oils and fats Cosmetics and oils form a film on the skin surface to play a role in protecting the skin, providing flexibility and lubricity, and providing cosmetics with an appropriate feeling of use. It is. In the present invention, cosmetic oils and fats similar to those used in general cosmetics such as emulsions and creams can be used, and examples thereof include the following.

・ Fats and oils (esters of higher fatty acids and glycerin) ... vegetable oils, animal fats and oils or hydrogenated products thereof (partially hydrogenated rapeseed oil, etc.), synthetic triglycerides (tri (capryl / capric acid) glyceryl, etc.), etc .;
・ Wax (esters of higher fatty acids and higher alcohols that are solid at room temperature): vegetable wax, animal wax (eg, beeswax, lanolin, etc.);
・ Hydrocarbons: mineral hydrocarbons (liquid paraffin, petrolatum, paraffin, etc.), animal hydrocarbons (squalane, etc.);
・ Higher fatty acids: Lauric acid, myristic acid, palmitic acid, stearic acid, oleic acid, isostearic acid, etc .;
・ Higher alcohol: cetanol, stearyl alcohol, lanolin alcohol, etc .;
Esters (esters of fatty acids and alcohols other than waxes): myristyl myristate, propylene glycol dioleate, cetyl lactate, etc.

  Among these cosmetic oils and fats, those recognized as foods or food additives such as beeswax are preferable cosmetic oils and fats in the present invention in that they do not pose a problem even if they adhere to foods, tableware, and cooking utensils. .

-Manufacturing method The manufacturing method of the composition for anti-viruses of this invention mix | blends an antiviral agent (oyster extract) as one of the manufacturing raw materials, and also mix | blends vitamin C as needed, These things It is the same as the conventional methods for producing alcohol preparations, cleaning agents, disinfectants, lotions, emulsions, creams, etc., except that appropriate adjustments are made. That is, in addition to the conventional (or fine-tuned if necessary) production raw materials of these conventional products, antiviral agents are blended, and the same as the conventional products (or fine-tuned as necessary) by the production process, The antiviral composition of the present invention can be produced. For example, if it takes the form of a cream, an antiviral agent and other ingredients are added to purified water to prepare an aqueous phase part, while an oil phase part composed of cosmetic fats and oils is prepared. What is necessary is just to manufacture so that it may mix in a predetermined ratio.

  The method of using the antiviral composition of the present invention is also the same as that for conventional alcohol preparations, cleaning agents, disinfectants, lotions, emulsions, creams and the like. Furthermore, for example, if it is a cleaning agent, it may be a concentrated type that is diluted when used, or if it is an alcohol preparation or disinfectant, in addition to a spray type, it may be impregnated into a non-woven fabric to be a wiping type. The antiviral composition of the present invention can be appropriately commercialized in a preferable mode depending on the method of use.

In addition, when mix | blending an organic acid and / or its salt with the antiviral agent or antiviral composition of this invention, the pH of those aqueous solution becomes like this. Preferably it is 5.0-2.0, More preferably, it is 4.8. It is preferable to add an organic acid and / or a salt thereof in an amount of -2.0, more preferably 4.0-2.0.
− Pharmaceuticals −
The antiviral agent of the present invention can be used as an active ingredient of a therapeutic or prophylactic agent for infectious diseases caused by enveloped viruses. Such pharmaceutical dosage forms can be appropriately selected from, for example, oral ingestion types such as liquids, syrups, tablets, capsules, powders, granules, and injections, and excipients as necessary. (For example, lactose and other sugars), binders (for example, starch, methylcellulose, polyvinyl alcohol), stabilizers (for example, ascorbic acid), preservatives (for example, paraoxybenzoic acid esters), sweeteners, solvents, and other various additives. It can be used in combination and manufactured according to a general formulation method. In addition, the effective dosage of these pharmaceuticals can be appropriately determined according to the patient's age, weight, symptoms, route of drug administration, administration schedule, formulation form, strength of inhibitory activity of the material, etc. What is necessary is just to adjust content of these antiviral agents according to those conditions.

  In addition, the antiviral agent of this invention and the pharmaceutical containing this can take not only the aspect administered to a human but the aspect administered to animals other than a human which can be infected with envelope viruses, such as mammals and fish. . For example, for fish, an antiviral agent or a medicine containing it can be mixed with the feed and administered orally, or by forced oral administration using a syringe or the like, or an antiviral agent added to the breeding water Thus, it is possible to take a method such as “medicine bath” where fish are kept for a certain time or at all times.

  Furthermore, the antiviral agent of the present invention may be used, for example, as a gargle or an oral spray after being diluted with water so as to have an appropriate concentration, and its use is not particularly limited.

[Example 1]
A drug according to the composition shown in Table 2 was prepared, and human influenza virus, avian influenza virus, and vesicular stomatitis virus were diluted as they were, and herpes simplex virus type 1 and Newcastle disease virus were further diluted in half with water. The following examples were used. As a control, phosphate buffered saline (PBS) was used. In addition, persimmon astringent FD powder (oyster extract) is sterilized by cutting the immature fruit of the persimmon that has been thoroughly sterilized (NaClO), washed, discoloration-prevented (vitamin C), etc. The obtained fruit / fruit juice solution was passed through a 200 mesh sieve, centrifuged, subjected to high temperature sterilization treatment (120 to 130 ° C., 7 to 10 seconds), and then prepared by freeze drying treatment.

  The virus solution of each test virus shown in Table 3 above and the drug or control shown in Table 2 above were mixed in an equivalent amount (35 μL each) and reacted at room temperature for 3 minutes, and then DMEM (Sulbecco's modified minimun A 10-fold serial dilution series was prepared using an essential medium). The diluted virus solution was inoculated into a monolayer culture cell of a 96-well plate (100 μL / well) and cultured. After 4 days, the CPE spread and fixed and stained, the 50% infection dose (unit: 50% tissue culture infections dose [TCID50]) was calculated using the Behrens-Kaerber method, and the virus infection titer was measured. The results are as shown in Table 4 and FIGS.

  All of the above five viruses are hardly affected by 20% or 10% (w / w) ethanol, but the infectivity titration is greatly reduced when blended with persimmon astringent FD powder, wattle tannin, or green tea tannin. Antiviral activity was confirmed. This result indicates that each of these substances is an excellent active ingredient against a wide range of enveloped viruses.

  Moreover, although pentagalloyl glucose was somewhat weak against vesicular stomatitis virus, antiviral activity against each virus was confirmed. Pyrogallol was also confirmed to have antiviral activity against four types of viruses except Newcastle disease virus. Furthermore, glycerin monocaprate was confirmed to have antiviral activity against all of the above five viruses, and citric acid / trisodium citrate was confirmed to have antiviral activity against four viruses excluding Newcastle disease virus.

  On the other hand, coffee tannin showed almost no antiviral activity against any of the above five viruses. Propyl gallate showed some antiviral activity depending on the type of virus.

[Example 2]
Viral hemorrhagic septic virus (VHSV) causes hemorrhagic sepsis in trout, but this disease has been confirmed recently in flounder and the like (Takano et al., 2001).

  Table 5 shows the test reagents. Each test reagent was adjusted to a concentration of 0.2% using Hanks' balanced salt solution (Nissui) (HBSS). To 50 μL of the reagent, 50 μL of various virus solutions were mixed (final reagent concentration 0.1%) and allowed to stand at room temperature for 2 minutes. Thereafter, the reaction was stopped by adding 9.9 mL of HBSS, and a 10-fold dilution series of these samples was prepared using HBSS.

  In the virus titer measurement test, FHM fish cultured cells (derived from Pimephales promelas) were first seeded in a 96-well plate (IWAKI) to 80% confluent, and 90 μL of the medium was added to each well and cultured for 24 hours. The medium used was MEM. Thereafter, 10 μL of the previously prepared dilution series was inoculated into each well and further cultured for 10 days to confirm the appearance of cytopathic effect (indicator of virus infection). The limiting dilution point at which no cytopathic effect was observed was confirmed, and the virus titer was measured according to the method of Reed and Muench (1938). The ratio of the virus titer of the test group to the virus titer (100%) of the control group was calculated to evaluate the antiviral activity (Table 6).

  For viral hemorrhagic sepsis virus, fermented koji juice (oyster extract), pentagalloyl glucose, wattle tannin, green tea tannin (catechins) and pyrogallol are highly effective, and these are excellent active ingredients. It has been shown that In addition, gallic acid and pentaploid tannin showed similar effects, and coffee tannin showed a certain effect.

[Example 3]
By mixing the following ingredients with stirring, an ethanol preparation, a hand-washing foam and a hand lotion could be prepared.

  Ethanol preparation (HA-72A): Kojibu FD powder 0.3 parts by weight / ethanol 50 parts by weight / citric acid 1.6 parts by weight / trisodium citrate 0.5% by weight / glycerin monocaprate 0.5 parts by weight / Water (remainder).

  Ethanol preparation: 0.3 parts by weight of strawberry astringent FD / 50 parts by weight of ethanol / 1.6 parts by weight of citric acid / 0.5 parts by weight of trisodium citrate / 0.5 parts by weight of glycerin monocaprate / 0.5% by weight of vitamin C Parts / water (remainder).

  Hand-washing foam: 0.1 parts by weight of isopropylmethylphenol / 0.5 parts by weight of persimmon FD powder / 20 parts by weight of 95% ethanol / Mydol 12 (manufactured by Kao Corporation. 7.0 parts by weight of lauryl glucoside) / 15 glycerin 0.0 part by weight / 1.0 part by weight of citric acid / 0.3 part by weight of glycerol monocaprate / 56.1 parts by weight of purified water.

  Hand-washing foam (KSF15-2): 0.1 parts by weight of isopropylmethylphenol / 0.5 parts by weight of persimmon FD powder / 18 parts by weight of 95% ethanol / Mydol 12 (produced by Kao Corporation. Lauryl glucoside) 7.0 Parts by weight / glycerin 15.0 parts by weight / citric acid 1.0 part by weight / glycerin monocaprate 0.3 part by weight / purified water 58.1 parts by weight.

  Hand lotion: Allantoin 0.1 part by weight / Dipotassium glycyrrhizinate 0.1 part by weight / Ashibu Shibu FD powder 0.3 part by weight / 95% ethanol 54.0 part by weight / Glycerin 2.0 part by weight / Citric acid 0.7 Parts by weight / trisodium citrate 0.3 parts by weight / glycerin monocaprate 0.3 parts by weight / purified water 42.0 parts by weight.

[Example 4]
(1) Agents used HA-72A and KSF15-2 prepared according to Example 3, and phosphate buffered saline (PBS) as a control
(2) Virus used Avian influenza virus A / swan / Shimane / 499/83 (H5N3)
(3) Cells
MDCK (+) cells
(Canine renal tubular epithelial cell origin: Noma K et al. Arch. Virol. 143: 1893-1909, 1998.)
(4) Virus infectivity titration method Equal volumes of virus solution and drug (35 μL each) were mixed, reacted at room temperature for 3 minutes, and 10-fold serial dilutions were prepared with DMEM (Dulbecco's modified minimum essential medium). . The diluted virus solution was inoculated into a monolayer culture cell of a 96-well plate (100 μL / well) and cultured. After 4 days, when the CPE spread, the cells were fixed and stained, the 50% infectious dose (unit: 50% tissue culture infectious dose [TCID50]) was calculated using the Behrens-Kaerber method, and the virus infectivity titer was measured.

  To examine the treatment time, the virus solution and the drug were mixed, and after a predetermined time (10, 30, 60 seconds), diluted with DMEM 500 times to stop the reaction with the drug. Was measured. The obtained infectious titer was corrected to 500 times.

(5) Results Action of drug:
In both HA-72A and KSF15-2, the viral activity decreased below the detection limit after 3 minutes of treatment. Since both drugs are toxic to cells to some extent, the result of “3.2E + 03 TCID50 / ml” is the limit for detecting the action of the virus.

Effect of processing time:
Since it is diluted 500 times, 1.6.E + 04 TCID50 / ml is the detection limit of virus activity. Therefore, it is considered that the virus activity has already decreased to 10 years after treatment. As described above, both reagents are inactivated (more than about 3000 times) so that the avian influenza virus cannot be detected. Also, it is considered effective at least for 10 seconds.

[Example 5]
(1) Agents used HA-72A and KSF15-2 prepared according to Example 3, and phosphate buffered saline (PBS) as a control
(2) Viruses and cells used

(3) Method for measuring virus infectivity titer Equal amounts of virus solution and drug (35 μL each) were mixed and reacted at room temperature for 3 minutes, and then a 10-fold serial dilution series was prepared with PBS. The diluted virus solution was inoculated into a monolayer culture cell of a 96-well plate (50 μL / well), and virus adsorption was performed for 30 minutes. Thereafter, the virus inoculum was removed by suction, and DMEM, 20 μg / ml trypsin (100 μL / well) was added. Six days later, when the CPE spread, the cells were fixed and stained, and a 50% infectious dose (unit: 50% tissue culture infectious dose [TCID50]) was calculated using the Behrens-Kaerber method, and the virus infectivity titer was measured.

(4) Results and discussion
Both HA-72A and KSF15-2 highly inactivated the H1N1 virus. Although the infection value of the original virus was not so high, it was the result that it was suppressed to 0.06% or less, but it may actually be highly inactivated.

[Example 6]
(1) Manufacturing method of aqueous juice liquid After washing and drying 330 g of raw material blue koji (chiba prefecture Chimoku rice, collected on August 22, 2009) to remove koji, the seeds were removed at the same time as cutting to about 2 cm square. (280 g). This was taken in a mixer and sufficiently ground with about 2.8 g (1%) of L-ascorbic acid (vitamin C) and 280 ml of purified water over about 3 minutes. This was squeezed several times with a non-woven fabric and heat-sterilized at 70-80 ° C. for about 30 minutes to obtain a pale yellow liquid (460 g). When this aqueous squeezed juice (processed oyster extract) was placed in a sealed container and placed at room temperature, it could be stored for a long period (at least 3 months) without producing off-flavors, discoloration, or precipitation.

Sugar content of strawberry flesh 9.4% (sugar content meter ATAGO Pal-1)
Tannin content 2.2% (quantitative Folin-Denis method)
(2) Manufacturing method of ethanolic juice After washing and drying 300 g of raw rice koji (Chiba Prefecture Hyakumoku, collected on August 22, 2009) to remove the koji, the seeds were removed at the same time as cutting to about 2 cm square. (260 g). This was taken up in a mixer and pulverized in about 3 portions with 2.6 g (1%) of L-ascorbic acid (vitamin C) and 260 ml (210 g) of 95% ethanol. When this was squeezed several times with a nonwoven fabric, a pale yellowish green liquid was obtained (430 g). When this ethanolic juice (treated product of oyster extract) was placed in a sealed container and placed at room temperature, it could be stored for a long period (at least 3 months) without causing off-flavors, discoloration, or precipitation.

Sugar content 9.5% (sugar content meter AYAGO Pal-1)
Tannin content 2.4% (quantitative Folin-Denis method)

Claims (11)

  It is obtained by inactivating the enzyme derived from the plant of the genus Diospyros which was contained in the juice or extract of the fruit of the genus Diospyros plant containing tannin by heating or treating with alcohol. An antiviral agent against an influenza virus belonging to the genus Influenza A, comprising the processed oyster extract as an active ingredient.   The antiviral agent according to claim 1, wherein the processed product of oyster extract contains at least condensed tannin.   The antiviral agent according to claim 1 or 2, wherein the plant of the genus Oyster is Diospyros kaki.   Further, at least one selected from the group consisting of catechins, wattle tannins, pentagalloyl glucose, pyrogallol, and organic acids and / or salts thereof (except those in the processed oyster extract) is effective. The antiviral agent according to any one of claims 1 to 3, which is contained as a component.   The antiviral agent according to any one of claims 1 to 4, which targets human influenza virus or avian influenza virus as the envelope virus of the influenza A genus. The antiviral alcohol formulation with respect to the envelope virus of the influenza A genus which contains the antiviral agent and alcohol in any one of Claims 1-5 at least. An antiviral cleaning composition for an influenza virus belonging to the genus influenza A virus, comprising at least the antiviral agent according to any one of claims 1 to 5 and a surfactant. A composition for antiviral disinfection against an enveloped virus of the influenza A genus, comprising at least the antiviral agent according to any one of claims 1 to 5 and an antibacterial agent (excluding ethanol, organic acids and salts thereof). .   The antiviral agent according to any one of claims 6 to 8, which contains a processed product of oyster extract (converted to solid content) in the antiviral agent at a ratio of 0.01 to 5% by weight with respect to the entire composition. Composition.   The antiviral composition according to any one of claims 6 to 9, comprising an organic acid and / or a salt thereof in such an amount that the composition has a pH of 6.0 to 2.0.   Furthermore, the antiviral composition in any one of Claims 6-10 containing vitamin C.