WO2010067869A1 - Anti-viral agent and anti-viral composition - Google Patents

Anti-viral agent and anti-viral composition Download PDF

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Publication number
WO2010067869A1
WO2010067869A1 PCT/JP2009/070764 JP2009070764W WO2010067869A1 WO 2010067869 A1 WO2010067869 A1 WO 2010067869A1 JP 2009070764 W JP2009070764 W JP 2009070764W WO 2010067869 A1 WO2010067869 A1 WO 2010067869A1
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Prior art keywords
virus
antiviral
composition
genus
antiviral agent
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PCT/JP2009/070764
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French (fr)
Japanese (ja)
Inventor
整 島本
泰 冲中
剛正 坂口
徹 辻
義昭 中井
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国立大学法人広島大学
アルタン株式会社
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Priority to JP2010542138A priority Critical patent/JP5670201B2/en
Publication of WO2010067869A1 publication Critical patent/WO2010067869A1/en

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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/44Ebenaceae (Ebony family), e.g. persimmon
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12Antivirals
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12Antivirals
    • A61P31/14Antivirals for RNA viruses
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12Antivirals
    • A61P31/14Antivirals for RNA viruses
    • A61P31/16Antivirals for RNA viruses for influenza or rhinoviruses
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12Antivirals
    • A61P31/20Antivirals for DNA viruses
    • A61P31/22Antivirals for DNA viruses for herpes viruses

Definitions

  • 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.
  • viral diseases are difficult to treat because antibiotics and the like do not show an effect, which is a big problem for animals such as humans and livestock.
  • 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.
  • compositions 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 No. 2005-232043: Patent Document 1), anticancer agent and anti-pneumonia virus agent obtained by further adding astringency to components such as peptide polysaccharides contained in ganoderma spores (Japanese Patent Laid-Open No. 2004-331641: Patent Document 2) Has been proposed.
  • Patent Document 3 describes an antibacterial composition containing a tannin substance, a fatty acid ester, a chelating agent, and the like ([Claim 1]). Examples thereof include tannic acid, pyrocatechin, gallic acid, persimmon tannin, tea tannin, pentaploid tannin and the like ([Claim 4]).
  • tannic acid pyrocatechin, gallic acid
  • persimmon tannin tea tannin
  • pentaploid tannin pentaploid tannin and the like
  • 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.
  • Patent Document 4 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.
  • the phenol derivative include gallic acid alkyl esters, (N-propyl gallate, n-octyl gallate, catechin gallate, gallocatechin gallate, epicatechin gallate, etc.) are exemplified.
  • 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.
  • HSV-1 herpes simplex virus type 1
  • VSV vesicular stomatitis virus
  • Patent Document 5 JP-T-2004-529889 discloses a C1-C3 alcohol (for example, ethanol) or a C2-C4 diol, and an acid (for example) sufficient to adjust the pH of the composition to 4.6 or less.
  • an acid for example
  • a composition containing an organic acid has an inactivating action of envelope virus.
  • the examples specifically show that a solution containing ethanol and hydrochloric acid, glycolic acid or succinic acid has antiviral activity against labial herpesvirus (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).
  • 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.
  • 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.
  • 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 of the genus Diospyros contained in the squeezed or extracted liquid of the fruit of the genus Diospyros plant 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 of the genus Oyster is Diospyros kaki.
  • the antiviral agent in any one.
  • 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.
  • An antiviral alcohol preparation containing at least the antiviral agent according to any one of [1] to [6] and an alcohol.
  • An antiviral cleaning composition comprising at least the antiviral agent according to any one of [1] to [6] and a surfactant.
  • An antiviral disinfecting composition comprising at least the antiviral agent according to any one of [1] to [6] and an antibacterial agent (excluding ethanol, organic acids and salts thereof).
  • the oyster extract processed product (in terms of solid content) in the antiviral agent is contained in a proportion of 0.01 to 5% by weight with respect to the total composition, [7] to [9] The antiviral composition as described.
  • the antiviral composition according to any one of [7] to [10] which contains an organic acid and / or a salt thereof in an amount that results in a pH of the composition of 6.0 to 2.0.
  • 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 (a processed product of oyster extract) is desirable, 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • an envelope virus such as spraying, applying, etc.
  • an antiviral agent or antiviral composition that is a substance containing the above-described components.
  • 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.
  • 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.
  • 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 the 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.
  • the antiviral composition of the present invention 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.
  • 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.
  • the antiviral agent and antiviral composition of the present invention can be applied to a wide range of enveloped viruses.
  • 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).
  • a fish disease virus it can apply to the following various envelope viruses, for example.
  • 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.
  • 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) ...
  • koi herpesvirus disease Viruses that have become very problematic in recent years.
  • Roniviridae single-stranded DNA virus, long spherical Okavirus Yellow head virus ... The causative agent of shrimp yellow head disease.
  • Nucleopolyhedrovirus (Nucleopolyhedrovirus) Monodon-type baculovirus (Penaeus monodon NPV): Cause of monodon-type baculovirus infection.
  • 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.
  • an extract of an oyster genus plant containing tannin that is, an oyster extract (sometimes referred to as persimmon shibutannin) is used.
  • 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
  • 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.
  • 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.
  • 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.
  • 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.
  • the alcohol treatment can be usually performed using 30-100%, preferably 50-100% alcohol such as ethanol.
  • alcohol such as ethanol
  • the aspect of the alcohol treatment step is not particularly limited.
  • 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.
  • 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.
  • pulverization freeze-dried powder is usually slightly yellow
  • 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.
  • the oyster extract in the present invention is a liquid obtained by squeezing immature astringency and then fermenting and aging for a long time (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.
  • 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).
  • a fermentation product obtained by adding an oyster-derived yeast culture solution to oyster juice and fermenting it at 20-25 ° C. for 1 to 3 months can be used (usually a reddish brown solution). It is preferable to store within.
  • Basic, manufacturing method, essence Oyster oyster Diospyros kaki THUNB.
  • the main components are tannin and tannic acid.
  • the additive described as oyster extract in the present invention is used. You can also
  • 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.
  • 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 at a ratio of about 1: 1: 2: 2 (see Matsuo & Itoo (1981a): Non-Patent Document 1 above).
  • 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), and is described in, for example, Matsuo & Itoo (1981b) (Non-Patent Document 2). It is also possible to purify and quantify by a method that has been developed.
  • 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.
  • 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.).
  • 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 contained in plants such as catechu (also known as gan beer, scientific name Acacia catechu) and tea tree (tea tree, scientific name: Camellia sinensis), which are shrubs of the leguminous acacia genus from India. 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.
  • (+)-catechin separated from catechu has the following structural formula (2).
  • catechins (sometimes referred to as “green tea tannin”) contained in tea tree are epicatechin [epicatechin, structural formula (3)] and its epigallocatechin [epigallocatechin, structural formula (4) )], And their gallic esters, epicatechin gallate [epicatechin gallate, structural formula (5)] and epigallocatechin gallate [epigallocatechin gallate, structural formula (6)], which are heated. It may be isomerized by treatment.
  • Catechins are also contained in other plants.
  • these compounds may be isolated and used from a plant containing catechins, or an extract of a plant containing catechins may be used.
  • 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.
  • 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.
  • 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.
  • Watru tannin is a tannin extracted from the bark, leaves, cocoons, etc. of plants of the genus Acacia. ), Derived from Acacia mearnsii (Black Wattle).
  • 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)
  • influenza A virus genus human influenza virus, avian influenza virus, etc.
  • simple virus genus simplex virus type 1 etc.
  • abular virus genus Newcastle disease
  • envelope viruses such as viruses and the like
  • 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 can also be used as an active ingredient.
  • 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.)
  • 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.
  • 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 can also be used as an active ingredient.
  • 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.
  • 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.
  • 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.
  • 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, and 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.
  • the 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 entire antiviral composition (including the solvent and the like).
  • the pH of the antiviral composition is usually 6.0 to 2.0, preferably 5.0 to 2.0, 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.).
  • an antiviral agent containing an organic acid and / or a salt thereof as an active ingredient when 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • the alcohol, surfactant, antibacterial agent, moisturizing agent, and cosmetic fats and oils may naturally be used in combination of two or more.
  • a surfactant such as a fatty acid ester
  • 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.
  • 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.
  • 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.
  • 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 based on 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”.
  • a liquid material such as an extract of persimmon fruit
  • the solid content dried in the liquid material
  • 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.
  • Persimmon fruit juice usually contains about 5-10% solids.
  • vitamin C 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.
  • 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 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.
  • 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 include cationic, anionic, zwitterionic and nonionic surfactants.
  • anionic surfactants it is preferable to use a surfactant and / or a nonionic surfactant.
  • anionic surfactant examples include soap (alkali salt of higher fatty acid), monoalkyl sulfate, alkyl polyoxyethylene sulfate, alkyl benzene sulfonate, monoalkyl phosphate, and the like.
  • nonionic surfactants include polyoxyethylene alkyl ethers, polyoxyethylene fatty acid esters, fatty acid partial esters of polyhydric alcohols (such as glycerin and sugar alcohol), and fatty acid diethanolamides.
  • 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.
  • 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 include 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.
  • antibiotics and synthetic antibacterial agents such as Escherichia coli, Staphylococcus aureus, MRSA, Salmonella, Vibrio parahaemolyticus, Pseudomonas aeruginosa, etc. Those are preferred.
  • 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.
  • 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.
  • 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.
  • 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 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.
  • 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.
  • 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):
  • 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. .
  • the manufacturing method of the composition for anti-viruses of this invention mix
  • blends an antiviral agent as one of the manufacturing raw materials
  • blends vitamin C as needed
  • 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 the same as that for conventional alcohol preparations, cleaning agents, disinfectants, lotions, emulsions, creams and the like.
  • 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.
  • the pH of the aqueous solution is preferably 5.0 to 2.0, more preferably 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.
  • lactose and other sugars 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.
  • 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.
  • 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.
  • envelope viruses such as mammals and 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
  • a method such as “medicine bath” where fish are kept for a certain time or at all times.
  • the antiviral agent of the present invention may be used, for example, as a gargle or an oral spray after being diluted with water to 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.
  • PBS phosphate buffered saline
  • persimmon astringent FD powder 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 (120 to 130 ° C., 7 to 10 seconds), and then freeze-dried and used.
  • the virus solution of each test virus shown in Table 3 above and each drug or control shown in Table 2 above were mixed in an equivalent amount (35 ⁇ L each) and reacted at room temperature for 3 minutes, and then DMEMD (Sulbecco's modified minimun Essential dilution medium) was used to prepare a 10-fold serial dilution series.
  • the diluted virus solution was inoculated into a monolayer culture cell of a 96-well plate (100 ⁇ L / well) and cultured. After 4 days, the CPE spread and fixed and stained, and the Behrens-Kaerber method was used to calculate the 50% infectious dose (unit: 50% tissue culture infections dose [TCID50]), and the virus infectivity titer was measured. The results are as shown in Table 4 and FIGS.
  • pentagalloylglucose 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.
  • 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.
  • VHSV Viral hemorrhagic septic virus
  • test reagents are shown in Table 5. Each test reagent was adjusted to a concentration of 0.2% using Hanks' balanced salt solution (Nissui) (HBSS). To 50 ⁇ L of the reagent, 50 ⁇ L 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 HBSS, and a 10-fold dilution series of these samples was prepared using HBSS.
  • HBSS Hanks' balanced salt solution
  • FHM fish cultured cells (derived from Pimephales® promelas) were seeded in a 96-well plate (IWAKI) to 80% confluent, and 90 ⁇ L of the medium was added to each well and cultured for 24 hours.
  • the medium used was MEM.
  • 10 ⁇ L of the previously prepared dilution series solution 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).
  • fermented koji juice oyster extract
  • pentagalloyl glucose wattle tannin
  • green tea tannin catechins
  • pyrogallol 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 ⁇ L 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). .
  • PBS phosphate buffered saline
  • the diluted virus solution was inoculated into a monolayer culture cell of a 96-well plate (100 ⁇ L / 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.
  • 50% infectious dose unit: 50% tissue culture infectious dose [TCID50]
  • the virus solution and the drug were mixed, and after a predetermined time (10, 30, 30 seconds), diluted with DMEM 500 times to stop the reaction with the drug. was measured.
  • the obtained infectious titer was corrected by multiplying by 500 tons.
  • 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
  • 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 ground sufficiently with 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 sterilized by heating 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.
  • aqueous squeezed juice processed oyster extract

Abstract

Disclosed is an anti-viral agent which has an excellent efficacy against enveloped viruses and is highly safe for human bodies.  Also disclosed is an anti-viral composition which contains the anti-viral agent and is useful for the eradication of the viruses or the prevention of infection by the viruses.  The anti-viral agent is characterized by comprising, as an active ingredient, a processed persimmon extract material which is produced by heating a tannin-containing squeezed juice or extract from a fruit of a Diospyros plant or treating the tannin-containing squeezed juice or extract with an alcohol to deactivate an enzyme derived from the Diospyros plant and contained in the squeezed juice or extract.  The anti-viral composition is characterized by comprising the anti-viral agent and an alcohol, a surfactant or an anti-bacterial agent.  Preferably, the anti-viral composition additionally contains vitamin C.

Description

抗ウイルス剤および抗ウイルス用組成物Antiviral agent and antiviral composition
 本発明は、エンベロープウイルス(たとえばヒト型インフルエンザウイルス、トリ型インフルエンザウイルス、単純ヘルペスウイルス1型、ニューカッスル病ウイルス、水疱性口内炎ウイルスなどのヒトまたは家畜の病原ウイルスや、ウイルス性出血性敗血症ウイルスなどの魚病ウイルス)に対する効果に優れかつ人体に対する安全性も高い、タンニンを含有するカキノキ属の植物の抽出物、カテキン類、ワットルタンニン、ペンタガロイルグルコース、コーヒータンニン、ピロガロール、没食子酸、五倍子タンニンなど有効成分とする抗ウイルス剤、およびこの抗ウイルス剤を含有し上記ウイルスの消毒や感染予防のために有用な抗ウイルス用組成物に関する。 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.
 一般的にウイルス病は、抗生物質などが効果を示さないため治療が困難であり、ヒトや家畜などの動物に対して大きな問題となっている。近年、SARSや鳥インフルエンザが話題となったことは記憶に新しいところである。また、養殖魚でもウイルス病が大きな問題となっているが、有効な治療法がなく、ワクチンによる予防が主な対策となっている。 In general, viral diseases are difficult to treat because antibiotics and the like do not show an effect, which is a big 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.
 ところで、柿の実の抽出液を発酵して得られる「柿渋」は、古くから中国において血圧降下等のために漢方薬として用いられ、日本においても民間薬として親しまれているものである。この柿渋はタンニンを豊富に含有し、収斂性(タンパク質等と結合して組織を引き締める性質)のほか、抗菌作用や消臭作用を有するといわれている。なお、カキノキに含有されるタンニン(縮合型タンニン)の構造や精製方法に関しては下記の2つの学術論文(Matsuo and Itoo, 1981a/1981b:非特許文献1および2)を参照することができる。 By the way, “Shibutsu” obtained by fermenting an extract of persimmon fruit has long been used as a Chinese herbal 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. In addition, regarding the structure and purification method of tannin (condensed tannin) contained in oysters, the following two academic papers (Matsuotooand Itoo, 1981a / 1981b: Non-Patent Documents 1 and 2) can be referred to.
 このような柿渋ないし柿のタンニンを含有する組成物としては、たとえば、柿渋抽出物をさらに取り扱い性や抗菌性を向上させるためにシクロデキストリンで包含した上で配合した抗菌性歯科用組成物(特開2005-232043号公報:特許文献1)、霊芝胞子に含まれるペプチド多糖類などの成分にさらに柿渋を添加混合した制癌剤および抗肺炎ビールス剤(特開2004-331641号公報:特許文献2)が提案されている。 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 No. 2005-232043: Patent Document 1), anticancer agent and anti-pneumonia virus agent obtained by further adding astringency to components such as peptide polysaccharides contained in ganoderma spores (Japanese Patent Laid-Open No. 2004-331641: Patent Document 2) Has been proposed.
 また、特開2006-206558号公報(特許文献3)には、タンニン物質、脂肪酸エステル類、キレート剤などを含有する抗菌性組成物が記載されており([請求項1])、当該タンニン物質としてはタンニン酸、ピロカテキン、没食子酸、柿タンニン、茶タンニン、五倍子タンニンなどが挙げられている([請求項4])。しかしながら、この抗菌性組成物の有効性は、タンニン酸を用いた場合における大腸菌および黄色ブドウ球菌に対してのものしか実証されておらず([実施例])、上記タンニン物質、特に柿タンニンが顕著なエンベロープウイルスに対する抗ウイルス性を有すること、したがって抗ウイルス用組成物の成分として極めて有用であることは何ら具体的に開示されていない。 Japanese Patent Application Laid-Open No. 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]). 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.
 特開2006-306836号公報(特許文献4)には、特定のフェノール誘導体が各種非エンベロープまたはエンベロープウイルスの不活性化剤として有効であると記載されており、フェノール誘導体としては没食子酸アルキルエステル、(n-プロピルガレート、n-オクチルガレート、カテキンガレート、ガロカテキンガレート、エピカテキンガレート等)が例示されている。しかしながら実施例では、単純ヘルペスウイルス1型(HSV-1)および水疱性口内炎ウイルス(VSV)に対してn-オクチルガレートが抗ウイルス活性を有することは具体的に示されているものの、緑茶タンニンに含まれるカテキンガレート等が抗ウイルス活性を有するかどうかは実証されていない。 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. Examples of the phenol derivative include gallic acid alkyl esters, (N-propyl gallate, n-octyl gallate, catechin gallate, gallocatechin gallate, epicatechin gallate, etc.) are exemplified. However, in the examples, although it is 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.
 特表2004-529889号公報(特許文献5)には、C1~C3アルコール(たとえばエタノール)またはC2~C4ジオールと、組成物のpHを4.6以下に調整するために十分な量の酸(たとえば有機酸)を含有する組成物がエンベロープウイルスの不活性化作用を有することが記載されている。しかしながら実施例では、口唇ヘルペスウイルス(HSV-1)に対してエタノールと塩酸、グリコール酸またはコハク酸とを含有する溶液が抗ウイルス活性を有することしか具体的に示されていない。 JP-T-2004-529889 (Patent Document 5) discloses a C1-C3 alcohol (for example, ethanol) or a C2-C4 diol, and an acid (for example) sufficient to adjust 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 labial herpesvirus (HSV-1).
 なお、本発明者らはこれまでに、カキ抽出物を用いた、食中毒および感染性胃腸炎の原因となるノロウイルスに対する抗ウイルス剤およびこれを用いた抗ノロウイルス性組成物(PCT/JP2008/060705)、ならびにカキ抽出物およびその他特定のタンニンないしタンニン様物質を用いた、非エンベロープウイルスに対する抗ウイルス剤およびこれを用いた抗ウイルス用組成物(PCT/JP2009/056635)を出願している。また、杉山ら(非特許文献3)は、柿渋タンニンが強い抗ノロウイルス性作用を示すことや、これを消毒剤(エタノール製剤)に用いることの可能性を記載している。 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).
特開2005-232043号公報JP 2005-232043 A 特開2004-331641号公報JP 2004-331641 A 特開2006-206558号公報JP 2006-206558 A 特開2006-306836号公報JP 2006-306836 A 特表2004-529889号公報Special table 2004-529889 gazette
 本発明は、エンベロープウイルスの不活性化作用に優れかつ人体に対する安全性も高い抗ウイルス剤、およびこの抗ウイルス剤を含有しそれらのウイルスの消毒や感染予防のために有用な抗ウイルス用組成物を提供することを目的とする。 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.
 本発明者らは、上記課題を解決するため、食品あるいは食品添加物として認められている物質や植物成分、すなわち口にしても安全な素材の中から抗ウイルス活性を有する物質の探索を行ったところ、タンニンを含有するカキノキ属の植物の抽出物が広範なエンベロープウイルスに対する顕著な抗ウイルス活性を有することを見出し、またその他のタンニンないしタンニン様物質や、クエン酸および/またはその塩などもエンベロープウイルスに対する抗ウイルス活性を有すること見出したことにより、本発明を完成させるに至った。 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.
 本発明の概要は下記のとおりである。
[1]タンニンを含有するカキノキ属(Diospyros)の植物の果実の搾汁または抽出液を加熱またはアルコールで処理することによりその中に含有されていた当該カキノキ属の植物に由来する酵素を失活させて得られた、カキ抽出物処理物を有効成分とする、エンベロープウイルスに対する抗ウイルス剤。
[2]前記カキ抽出物処理物が少なくとも縮合型タンニンを含有するものである、[1]に記載の抗ウイルス剤。
[3]前記カキノキ属の植物がカキノキ(Diospyros kaki)である、[1]または[2]に記載の抗ウイルス剤。
[4]さらに、カテキン類、ワットルタンニン、ペンタガロイルグルコース、コーヒータンニン、ピロガロール、没食子酸、五倍子タンニン、および有機酸および/またはその塩(前記カキ抽出物処理物中のものを除く。)からなる群から選ばれた少なくとも1種を有効成分として含有する、[1]~[3]のいずれかに記載の抗ウイルス剤。
[5]前記エンベロープウイルスとして、A型インフルエンザウイルス属、ベシクロウイルス属、単純ウイルス属、アビュラウイルス属、またはノビラブドウイルス属に属するエンベロープウイルスを対象とする、[1]~[4]のいずれかに記載の抗ウイルス剤。
[6]前記エンベロープウイルスとして、ヒト型インフルエンザウイルス、トリ型インフルエンザウイルス、水疱性口内炎ウイルス、単純ヘルペスウイルス1型、ニューカッスル病ウイルス、またはウイルス性出血性敗血症ウイルスを対象とする、[5]に記載の抗ウイルス剤。
[7]少なくとも[1]~[6]のいずれかに記載の抗ウイルス剤とアルコールとを含有する、抗ウイルス用アルコール製剤。
[8]少なくとも[1]~[6]のいずれかに記載の抗ウイルス剤と界面活性剤とを含有する、抗ウイルス洗浄用組成物。
[9]少なくとも[1]~[6]のいずれかに記載の抗ウイルス剤と抗菌剤(エタノール、有機酸およびその塩を除く。)とを含有する、抗ウイルス消毒用組成物。
[10]前記抗ウイルス剤中のカキ抽出物処理物(固形分換算)を組成物全体に対して0.01~5重量%の割合で含有する、[7]~[9]のいずれかに記載の抗ウイルス用組成物。
[11]有機酸および/またはその塩を組成物のpHが6.0~2.0となる量で含有する、[7]~[10]のいずれかに記載の抗ウイルス用組成物。
[12]さらにビタミンC類を含有する、[7]~[11]のいずれかに記載の抗ウイルス用組成物。
The outline of the present invention is as follows.
[1] Depressing the enzyme derived from the plant of the genus Diospyros contained in the squeezed or extracted liquid of the fruit of the genus Diospyros plant 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 of 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 as an active ingredient at least one selected from the group consisting of:
[5] The envelope virus according to [1] to [4], wherein the envelope virus belongs to the genus influenza A, vesiculovirus, simple virus, aburavirus, or nobirabrado. 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 comprising 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] The oyster extract processed product (in terms of solid content) in the antiviral agent is contained in a proportion of 0.01 to 5% by weight with respect to the total composition, [7] to [9] 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 an amount that results in a pH of the composition of 6.0 to 2.0.
[12] The antiviral composition according to any one of [7] to [11], further comprising vitamin C.
 本発明の抗ウイルス剤を構成するカキ抽出物としては、カキノキ属の植物の果実の搾汁または抽出液を、加熱またはアルコールで処理することにより、その中に含有されていた当該カキノキ属の植物に由来する酵素を失活させて得られたもの(カキ抽出物処理物)が望ましく、また、少なくとも縮合型タンニンを含有するもの、たとえばカキノキ(Diospyros kaki)から得られるものが好ましい。 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 (a processed product of oyster extract) is desirable, and one containing at least condensed tannin, for example, one obtained from Diospyros kaki is preferable.
 また、本発明の抗ウイルス剤としては、対象とするエンベロープウイルスによっては、カキ抽出物の他、カテキン類(カテキン、エピカテキン、エピガロカテキン、エピカテキンガレート、エピガロカテキンガレート等)、ワットルタンニン、ペンタガロイルグルコース、コーヒータンニン、ピロガロール、没食子酸、五倍子タンニンなどを有効成分として使用することもできる。さらに、有機酸および/またはその塩(前記カキ抽出物またはその処理物中のものを除く。)を抗ウイルス剤の有効成分として使用することもできる。これらの抗ウイルス剤の有効成分は、それぞれ1種単独で用いても、複数を組み合わせて用いてもよい。 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.
 このような抗ウイルス剤は、アルコール、界面活性剤、抗菌剤(エタノール、有機酸およびその塩を除く。)、保湿剤、化粧品用油脂類などと組み合わせた組成物の、エンベロープウイルスに対する有効成分として使用することが好適である。 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.
 すなわち、本発明の抗ウイルス用組成物は、上記抗ウイルス剤と、アルコール、界面活性剤、抗菌剤、保湿剤および化粧品用油脂類からなる群より選ばれた少なくとも1種とを含有することを特徴とする。このような抗ウイルス用組成物は、前記抗ウイルス剤(固形分換算)を組成物全体に対して0.01~5重量%の割合で含有することが好ましい。また、有機酸および/またはその塩を組成物のpHが6.0~2.0となる量で含有することも好ましい。さらに上記の抗ウイルス用組成物は、ビタミンC類を含有することも好ましい。 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.
 たとえば、本発明の抗ウイルス用組成物は、少なくとも前記抗ウイルス剤とアルコールとを含有する抗ウイルス用アルコール製剤、少なくとも前記抗ウイルス剤と界面活性剤とを含有する抗ウイルス洗浄用組成物、少なくとも前記抗ウイルス剤と抗菌剤とを含有する抗ウイルス消毒用組成物として提供される。 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.
 換言すれば、本発明は、上述のような成分を含有する物質である抗ウイルス剤または抗ウイルス用組成物を、エンベロープウイルスによる汚染の可能性がある場所に噴霧、塗布等するなど、エンベロープウイルスの消毒または感染予防のために使用する方法を提供する。 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.
 さらに、本発明の抗ウイルス剤は、エンベロープウイルスに起因する感染症の治療剤または予防剤の有効成分として使用することもできる。すなわち、本発明のエンベロープウイルスに対する感染症の治療剤または予防剤は、上記抗ウイルス剤を有効成分として含有することを特徴とする。 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.
 本発明の抗ウイルス剤として用いるカキ抽出物、カテキン類、ワットルタンニン、ペンタガロイルグルコース、コーヒータンニン、ピロガロール、没食子酸、五倍子タンニン、あるいは有機酸および/またはその塩の、エンベロープウイルスに対する効果は、一般的な抗菌剤等と比較して格段に優れており、それらのウイルスを99%以上消滅させることも可能である。通常、ウイルスはその種類の違いによって、その構造が異なるため、種類ごとに、化学物質や薬品等に対する挙動もしくは耐性が異なるものとされているが、特にカキ抽出物を少なくとも用いた抗ウイルス剤にあっては、そのウイルスの種類によらず、広い範囲のウイルスに対しても効果があるという特徴を有する。また、このような抗ウイルス剤は、そのまま単独で使用することができる物質であるのみならず、アルコール製剤、洗浄用組成物、ハンドソープ、消毒用組成物、ローション、乳液、クリーム等の組成物、あるいはエンベロープウイルスに対する医薬品などの有効成分としても極めて有用である。そして、本発明の抗ウイルス剤またはそれを含有する組成物を、対象とするエンベロープウイルスが付着しているまたは付着している可能性のある場所(一般的には非生体および生体の表面であるが、組成物が医薬品である場合は生体の体内である場合もある)に接触させるようにして、消毒または感染予防のために用いることができる。 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 the 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.
 また、カキ抽出物(カキタンニン)などは食品添加物として認められているため、本発明の抗ウイルス用組成物の全ての成分を食品または食品添加物で構成し、食品・食器類に付着して口にされても問題にならない組成物とすることが可能となる。このようなカキ抽出物などを有効成分とする本発明の抗ウイルス用組成物を用いることにより、食品を取り扱う状況下や医療機関などにおいて、エンベロープウイルスの消毒や感染予防を効率的に行うことができるようになり、それらのウイルスに起因する疾患の発生を大幅に抑制することができるものと期待される。 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.
図1は、実施例1におけるヒト型インフルエンザウイルスに対する各種薬剤の抗ウイルス活性を示す。FIG. 1 shows the antiviral activity of various drugs against human influenza virus in Example 1. 図2は、実施例1におけるトリ型インフルエンザウイルスに対する各種薬剤の抗ウイルス活性を示す。FIG. 2 shows the antiviral activity of various drugs against the avian influenza virus in Example 1. 図3は、実施例1における水疱性口内炎ウイルスに対する各種薬剤の抗ウイルス活性を示す。FIG. 3 shows the antiviral activity of various drugs against vesicular stomatitis virus in Example 1. 図4は、実施例1における単純ヘルペスウイルス1型に対する各種薬剤の抗ウイルス活性を示す。FIG. 4 shows the antiviral activity of various drugs against herpes simplex virus type 1 in Example 1. 図5は、実施例1におけるニューカッスル病ウイルスに対する各種薬剤の抗ウイルス活性を示す。FIG. 5 shows the antiviral activity of various drugs against Newcastle disease virus in Example 1. 図6は、実施例4におけるトリ型インフルエンザウイルスに対する各種薬剤の抗ウイルス活性を示す。FIG. 6 shows the antiviral activity of various drugs against avian influenza virus in Example 4. 図7は、実施例5におけるヒト型インフルエンザウイルスに対する各種薬剤の抗ウイルス活性を示す。FIG. 7 shows the antiviral activity of various drugs against human influenza virus in Example 5.
 - エンベロープウイルス -
 本発明の抗ウイルス剤および抗ウイルス用組成物は、広範なエンベロープウイルスに対して適用することができる。たとえば、ヒトまたは家畜(ほ乳類・鳥類)の病原ウイルスとして知られている、表1の各種エンベロープウイルスに適用することができる。
-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).
Figure JPOXMLDOC01-appb-T000001
Figure JPOXMLDOC01-appb-T000001
 また、魚病ウイルスとしては、たとえば次の各種エンベロープウイルスに適用できる。
(1)ラブドウイルス科(Rhabdoviridae)、1本鎖RNAウイルス、砲弾型
 ノビラブドウイルス属(Novirhabdoviridae)
  ウイルス性出血性敗血症ウイルス(Viral hemorrhagic septicemia virus)…淡水魚では主にサケ科魚類、海産魚ではヒラメ等にウイルス性出血性敗血症を起こす。
(2)ヘルペスウイルス科(Herpesviridae)、2本鎖DNAウイルス、球形
 イクタルリウイルス属(Ictalurivirus)
  アメリカナマズヘルペスウイルス(Ictalurid herpesvirus 1)…アメリカナマズウイルス病の原因体/コイヘルペスウイルス(Koi herpesvirus)(属不明、未分類)…コイヘルペスウイルス病の原因体。近年、非常に問題となっているウイルス。
(3)レオウイルス科(Reoviridae)、2本鎖RNAウイルス、球形
 アクアレオウイルス属(Aquareovirus)
  種不明…金魚の転覆病。
(4)ニマウイルス科(Nimaviridae)、2本鎖DNAウイルス、長球形
 ウィスポウイルス属(Whispovirus)
  ホワイトスポット症候群ウイルス(White spot syndrome virus)…エビ類のホワイトスポット症候群の原因体。
(5)ロニウイルス科(Roniviridae)、1本鎖DNAウイルス、長球形
 オカウイルス属(Okavirus)
  イエローヘッド病ウイルス(Yellow head virus)…エビ類のイエローヘッド病の原因体。
(6)バキュロウイルス科(Baculoviridae)、2本鎖DNAウイルス、不定形。
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.
 ヌクレオポリヘドロウイルス属(Nucleopolyhedrovirus)
  モノドン型バキュロウイルス(Penaeus monodon NPV)…モノドン型バキュロウイルス感染症の原因体。
Nucleopolyhedrovirus (Nucleopolyhedrovirus)
Monodon-type baculovirus (Penaeus monodon NPV): Cause of monodon-type baculovirus infection.
 - 抗ウイルス剤 -
 本発明の抗ウイルス剤の有効成分は、対象とするエンベロープウイルスに応じて、カキ抽出物、カテキン類、ワットルタンニン、ペンタガロイルグルコース、コーヒータンニン、ピロガロール、没食子酸、五倍子タンニンなどの中から適切なものを選択することができる。
-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.
  ・カキ抽出物
 本発明では、広範なエンベロープウイルスに対する抗ウイルス剤の有効成分として、タンニンを含有するカキノキ属の植物の抽出物、すなわちカキ抽出物(柿シブタンニンとよばれることもある。)を用いる。なお、このカキ抽出物は、タンニンを含有するカキノキ属の植物に由来する物質のみならず、これを抽出するために用いた溶媒等を含有していてもよい。
-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.
 カキ抽出物の原料は特に限定されるものではないが、カキタンニン(特に縮合型タンニン)を豊富に含む渋柿(たとえばカキノキの蜂屋、平種無などの品種)の未成熟果を用いると効率的かつ経済的である。また、同様の成分からなるカキ抽出物が得られるのであれば、カキノキ属の植物の葉や樹皮など果実以外の部位を原料としてもよい。 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.
 このような原料からカキ抽出物を調製する方法も特に限定されるものではないが、一般的には、蔕を除去した渋柿を、粉砕、圧搾して搾汁を回収する方法、または適度な大きさに切断してからミキサーにかけて液状にし、さらに遠心分離機にかけて上澄み液を回収する方法、あるいは水または水系溶媒で抽出して抽出液を回収する方法などが用いられる。 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.
  ・加熱、アルコールおよびその他の処理
 本発明のカキ抽出物としては、上述のようなカキノキ属の植物の果実の搾汁や抽出液をそのまま用いることもできるが、それらの加熱またはアルコールによる処理物(以下「カキ抽出物処理物」とよぶこともある。)を用いることが望ましい。加熱またはアルコール処理によりカキ抽出物の抗ウイルス性は一層高まり、あわせて抗ウイルス性を検証するための測定が阻害されることを防止できるようになる。このようなカキ抽出物処理物は比較的容易に調製することができ、かつ組成物の成分として使用する上で色や臭気がほとんど問題にならないという利点を有し、発酵に時間がかかる上に色や臭気の点で使用しにくい面のある柿渋(後述)よりも工業的に利用しやすい。また、上記のように加熱またはアルコール処理により、長期間保存しておいても、変色や沈殿等といったことが生じることはない。
-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.
 加熱処理の温度および時間条件は、搾汁等に含有されているカキノキ属の植物に由来する酵素を失活させることができる程度の条件であればよく、植物の酵素を失活させるための一般的な条件を採用することができる。すなわち、温度は通常60~130℃、時間は通常5秒~30分であり、たとえば、120℃~130℃で5~10秒間、あるいは約85℃で5~15分間などの条件で加熱処理を行えばよい。また、加熱処理工程の態様は特に限定されるものではなく、たとえば搾汁を殺菌する工程における加熱や、粉末化する工程における加熱、あるいは柿渋(詳細は後述)を製造するための発酵開始前の加熱などによって当該処理を行うことができる。 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.
 一方、アルコール処理は、通常30~100%、好ましくは50~100%のエタノール等のアルコール類を用いて行うことができる。たとえば、カキ絞汁液に95v/v%エタノールを同量程度添加するように処理し、その後は密閉遮光容器内で保存することが好ましい(通常淡褐色の液となる)。また、アルコール処理工程の態様も特に限定されるものではなく、たとえばエタノール等のアルコール系溶媒を用いて抽出をする工程は当該アルコール処理工程に相当するほか、典型的には本発明の抗ウイルス用組成物としてのアルコール製剤を製造するための一工程として、必要に応じて上記の加熱処理が施されたカキ抽出物にアルコールを添加して混合することにより行うこともできる。なお、このようなアルコール処理は、カキ抽出物自体に含有される雑菌を殺菌する作用も併せ持つ。 On the other hand, the alcohol treatment can be usually performed using 30-100%, preferably 50-100% 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.
 本発明のカキ抽出物については、上記のような処理の他に、あるいは上記のような処理に加えて、発明の効果を阻害しない範囲で必要に応じて、濃縮、乾燥または凍結乾燥による固形化ならびに粉砕による粉末化(凍結乾燥粉末は通常微黄色である)、あるいはイオン交換樹脂等を用いた精製などの処理を施してもよい。カキ抽出物はポリフェノールを多く含有し、液状のままでは着色等の変質が起こりやすいため、凍結乾燥法を用いて固形状態で冷凍保存することが望ましい。これらの操作は、カキ抽出物に含有されるカキタンニンやその他の成分が分解されないような、温和な条件下で行うことが好ましい。 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.
 また、本発明におけるカキ抽出物としては、未成熟の渋柿の搾汁したのち長期間(1~3年程度)発酵、熟成させて得られる液体であって、数パーセント程度の固形分(カキタンニン)および発酵により生成した有機酸などを含有する「柿渋」を利用してもよい。この柿渋は従来民間薬や塗料などとして利用されており、たとえば「柿渋」(冨山柿渋製造場)などの商品として一般的に市販されている。あるいは、カキ絞汁液にカキ由来の酵母培養液を加え、20~25℃で1~3ヶ月間発酵させて得られる発酵物を用いることもでき(通常赤褐色の液となる)、その後は密閉容器内で保存することが好ましい。 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 time (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, a fermentation product obtained by adding an oyster-derived yeast culture solution to oyster juice and fermenting it at 20-25 ° C. for 1 to 3 months can be used (usually a reddish brown solution). It is preferable to store within.
 なお、日本の食品衛生法に基づく「既存添加物名簿収載品目リスト」に「柿タンニン」(品名/別名=柿渋、柿抽出物。基原・製法・本質=カキ科カキ Diospyros kaki THUNB. の実より、搾汁したもの、又は水若しくはエタノールで抽出して得られたものである。主成分はタンニン及びタンニン酸である。)として記載されている添加物を、本発明におけるカキ抽出物として利用することもできる。 In addition, the “list of existing additives listed in the Food Sanitation Law of Japan” 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
  ・カキタンニン
 カキノキ属(Diospyros)の植物、特にその果実には、収斂性や金属イオンと結合するなど所定の性質を有し、渋味を感じさせるもととなる物質、いわゆるタンニンと総称される化合物が豊富に含まれている。このようなカキタンニンには、多くの場合、カテキン、ガロカテキンおよびこれらの没食子酸エステルが結合してなる、下記推定構造式(I)で表される「カキ縮合型タンニン」が主要な成分として含まれていることが特徴的である。たとえば、カキノキ属の植物のうち、中国原産で日本をはじめ世界的に広く栽培されているカキノキ(Diospyros kaki)の果実に含まれているカキ縮合型タンニンは、カテキン、カテキンガレート、ガロカテキンおよびガロカテキンガレートがおよそ1:1:2:2の比率で炭素-炭素結合で縮合している高分子化合物である(Matsuo & Itoo (1981a):前出非特許文献1参照)。
-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 at a ratio of about 1: 1: 2: 2 (see Matsuo & Itoo (1981a): Non-Patent Document 1 above).
Figure JPOXMLDOC01-appb-C000002
Figure JPOXMLDOC01-appb-C000002
 また、カキタンニンには、上記「カキ縮合型タンニン」以外にも、カテキンや加水分解型タンニンなどその他のタンニン性化合物が含まれていることもある。 Further, oyster tannins may contain other tannic compounds such as catechins and hydrolyzable tannins in addition to the above “oyster condensed tannins”.
 なお、加水分解型タンニンは、アルコール(グルコース等)とカルボン酸(没食子酸等)とのエステルまたはそのオリゴマーであって、加水分解により低分子化されるのに対し、カキ縮合型タンニンは加水分解によって低分子化しないため(重合体の基本骨格の炭素-炭素結合は加水分解されない)加水分解型タンニンと区別することができ、たとえばMatsuo & Itoo (1981b)(前出非特許文献2)に記載された方法などにより精製、定量することも可能である。 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), and is described in, for example, Matsuo & Itoo (1981b) (Non-Patent Document 2). It is also possible to purify and quantify by a method that has been developed.
 本発明におけるエンベロープウイルスに対する抗ウイルス性の発現のためには、カキ抽出物中に少なくともカキ縮合型タンニンが含まれていることが好ましいと推測されるが、カキ抽出物中のその他の成分の寄与の可能性は何ら排除されるものではない。カキノキの果実を用いて後述のような調製方法により得られるカキ抽出物等には、通常自ずとカキ縮合型タンニンが含まれており、本発明の抗ウイルス剤は、そのようなカキ抽出物等を原料として用いて製造することが好適であると推測される。 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.
  ・カテキン類
 本発明の抗ウイルス剤が、A型インフルエンザウイルス属(ヒト型インフルエンザウイルス、トリ型インフルエンザウイルス等)、ベシクロウイルス属(水疱性口内炎ウイルス等)、単純ウイルス属(単純ヘルペスウイルス1型等)、アビュラウイルス属(ニューカッスル病ウイルス等)、ノビラブドウイルス属(ウイルス性出血性敗血症ウイルス等)などのエンベロープウイルスを対象とする場合、カテキン類を有効成分として使用することもできる。
-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.).
 カテキン類は、インド産のマメ科アカシア属の低木であるカテキュー(ガンビールとも呼ばれる。学名Acacia catechu)やチャノキ(茶の木、学名:Camellia sinensis)等の植物に含有される、3,5,7,3′,4′-ペンタヒドロキシフラバン(狭義のカテキン)、3,5,7,3′,4′,5′-ヘキサヒドロキシフラバン(ガロカテキン)およびそれらの3-ガロイル誘導体の総称であり、これらの立体異性体も含まれる。たとえばカテキューから分離される(+)-カテキンは、下記構造式(2)を有する。 Catechins are contained in plants such as catechu (also known as gan beer, scientific name Acacia catechu) and tea tree (tea tree, scientific name: Camellia sinensis), which are shrubs of the leguminous acacia genus from India. 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).
Figure JPOXMLDOC01-appb-C000003
Figure JPOXMLDOC01-appb-C000003
 また、チャノキに含有されるカテキン類(「緑茶タンニン」とよばれることもある。)は、エピカテキン[epicatechin、構造式(3)]とそのヒドロキシ体のエピガロカテキン [epigallocatechin、構造式(4)]、それらの没食子酸エステルであるエピカテキンガレート[epicatechin gallate、構造式(5)]およびエピガロカテキンガレート[epigallocatechin gallate、構造式(6)]を主成分とするが、これらの化合物は加熱処理により異性化することもある。 In addition, catechins (sometimes referred to as “green tea tannin”) contained in tea tree are epicatechin [epicatechin, structural formula (3)] and its epigallocatechin [epigallocatechin, structural formula (4) )], And their gallic esters, epicatechin gallate [epicatechin gallate, structural formula (5)] and epigallocatechin gallate [epigallocatechin gallate, structural formula (6)], which are heated. It may be isomerized by treatment.
Figure JPOXMLDOC01-appb-C000004
Figure JPOXMLDOC01-appb-C000004
Figure JPOXMLDOC01-appb-C000005
Figure JPOXMLDOC01-appb-C000005
Figure JPOXMLDOC01-appb-C000006
Figure JPOXMLDOC01-appb-C000006
Figure JPOXMLDOC01-appb-C000007
Figure JPOXMLDOC01-appb-C000007
 カテキン類はその他の植物にも含有されている。本発明では、カテキン類を含有する植物からこれらの化合物を単離して利用しても、カテキン類を含有する植物の抽出物を利用してもよい。また、カテキン類は、いずれか1種を単独で用いても、2種以上を組み合わせて用いてもよい。チャノキに含有されるカテキン類を利用することが最も好都合である。 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.
  ・ワットルタンニン
 本発明の抗ウイルス剤が、A型インフルエンザウイルス属(ヒト型インフルエンザウイルス、トリ型インフルエンザウイルス等)、ベシクロウイルス属(水疱性口内炎ウイルス等)、単純ウイルス属(単純ヘルペスウイルス1型等)、アビュラウイルス属(ニューカッスル病ウイルス等)、ノビラブドウイルス属(ウイルス性出血性敗血症ウイルス等)などのエンベロープウイルスを対象とする場合、さらにワットルタンニンを有効成分として使用することもできる。
-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.
 ワットルタンニンはアカシア属の植物の樹皮、葉、莢などから抽出されるタンニンであり、たとえばAcacia pycnantha(Golden Wattle), Acacia decurrens(Tan Wattle), Acacia dealbata(Silver Wattle、ミモザワットルとよばれることもある。), Acacia mearnsii (Black Wattle)などに由来するものが挙げられる。 Watru tannin is a tannin extracted from the bark, leaves, cocoons, etc. of plants of the genus Acacia. ), Derived from Acacia mearnsii (Black Wattle).
  ・ペンタガロイルグルコース
 本発明の抗ウイルス剤が、A型インフルエンザウイルス属(ヒト型インフルエンザウイルス、トリ型インフルエンザウイルス等)、単純ウイルス属(単純ヘルペスウイルス1型等)、アビュラウイルス属(ニューカッスル病ウイルス等)、ノビラブドウイルス属(ウイルス性出血性敗血症ウイルス等)などのエンベロープウイルスを対象とする場合、さらにペンタガロイルグルコースを有効成分として使用することもできる。
-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.
 ペンタガロイルグルコースは、グルコースの水酸基(1,2,3,4および6位)に没食子酸がエステル結合した化合物であり、たとえば五倍子タンニンを原料として分解、精製することにより得られる。 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.
  ・コーヒータンニン
 本発明の抗ウイルス剤が、ノビラブドウイルス属(ウイルス性出血性敗血症ウイルス等)などのエンベロープウイルスを対象とする場合、さらにコーヒータンニンを有効成分として使用することもできる。
-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.
 コーヒータンニンは、コーヒー豆等から抽出されるタンニン(ないしタンニン様物質)であり、主としてクロロゲン酸類(キナ酸の水酸基(3,4または5位のいずれか1つ以上)にカフェ酸がエステル結合した化合物)が含まれている。 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).
  ・ピロガロール
 本発明の抗ウイルス剤が、A型インフルエンザウイルス属(ヒト型インフルエンザウイルス、トリ型インフルエンザウイルス等)、ベシクロウイルス属(水疱性口内炎ウイルス等)、単純ウイルス属(単純ヘルペスウイルス1型等)、ノビラブドウイルス属(ウイルス性出血性敗血症ウイルス等)などのエンベロープウイルスを対象とする場合、さらにピロガロール(1,2,3-トリヒドロキシベンゼン)を有効成分として使用することもできる。
・ 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.
  ・没食子酸
 本発明の抗ウイルス剤がノビラブドウイルス属(ウイルス性出血性敗血症ウイルス等)などのエンベロープウイルスを対象とする場合、有効成分として没食子酸を使用することもできる。
-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.
  ・五倍子タンニン
 本発明の抗ウイルス剤がノビラブドウイルス属(ウイルス性出血性敗血症ウイルス等)などのエンベロープウイルスを対象とする場合、有効成分として、五倍子(ヌルデの虫こぶ)に由来する、五倍子タンニンを使用することもできる。
-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.
  ・有機酸および/またはその塩
 本発明の抗ウイルス剤が、A型インフルエンザウイルス属(ヒト型インフルエンザウイルス、トリ型インフルエンザウイルス等)、ベシクロウイルス属(水疱性口内炎ウイルス等)、単純ウイルス属(単純ヘルペスウイルス1型等)、ノビラブドウイルス属(ウイルス性出血性敗血症ウイルス等)などのエンベロープウイルスを対象とする場合、カキ抽出物に含まれているもの以外の有機酸および/またはその塩を有効成分として使用することもできる。
-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.
 なお、有機酸および/またはその塩は、細菌類に対する抗菌性にも優れた物質で、食品添加物としても認められており、タンニンの溶解性を高めるほか、タンニンが鉄と接触したときの着色を防止するキレート剤としても作用する。そのような観点から、本発明の抗ウイルス用組成物に有機酸および/またはその塩を配合することも好ましい。 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.
 有機酸および/またはその塩としては、炭素原子数2~10の有機酸および/またはその塩が好ましく、炭素原子数2~10のヒドロキシル基を含有する有機酸および/またはその塩がより好ましい。さらに具体的には、乳酸、リンゴ酸、クエン酸、酒石酸、サリチル酸、コハク酸、フマル酸およびイタコン酸からなる群から選ばれた少なくとも1種の有機酸および/またはその塩が好ましく、とくにクエン酸またはその塩が好ましい。また、有機酸の塩としては、上記有機酸のナトリウム塩、カリウム塩等が好ましい。 The organic acid and / or salt thereof is preferably an organic acid having 2 to 10 carbon atoms and / or a salt thereof, and 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.
 本発明の抗ウイルス用組成物に、特定のエンベロープウイルスに対する有効成分としておよび/または上記のようなその他の目的のために、有機酸および/またはその塩を配合する場合、有機酸および/またはその塩の割合は、抗ウイルス用組成物全体(溶媒等を含む。)に対して、0.05~5.0重量%が好ましく、0.1~2.0重量%がより好ましい。あるいは、抗ウイルス用組成物のpHが、通常は6.0~2.0となる量で、好ましくは5.0~2.0となる量で、より好ましくは4.8~2.0となる量で、さらに好ましくは4.0~2.0となる量で配合すればよい。水溶液のpHは、一般的なpHメーター(たとえばベックマン・コールター株式会社製のpHメーター)を使用して測定すればよい。 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 entire 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, 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.).
 なお、有機酸および/またはその塩を有効成分とする抗ウイルス剤を単独で用いる場合は当該抗ウイルス剤自体のpHを上記範囲で調整することが好ましいが、抗ウイルス剤を抗ウイルス用組成物に配合して(希釈して)用いる場合は、当該組成物の最終的なpHが上記好ましい範囲となるよう、必要に応じて抗ウイルス剤自体のpHはあらかじめ上記範囲よりも低い範囲で調整しておいてもよい。 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.
 - 抗ウイルス用組成物 -
 本発明の抗ウイルス用組成物は、エンベロープウイルスに対する有効成分としての抗ウイルス剤と、アルコール、界面活性剤、抗菌剤、保湿剤、または化粧品用油脂類のいずれか1種以上の成分とを含有し、必要に応じてさらにクエン酸および/またはその塩やビタミンC類を含有する組成物である。その態様は特に限定されるものではないが、代表的には以下のようなものが挙げられる。
-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.
 ・ 少なくとも抗ウイルス剤とアルコールとを含有するアルコール製剤
 ・ 少なくとも抗ウイルス剤と界面活性剤とを含有する洗浄用組成物
 ・ 少なくとも抗ウイルス剤と抗菌剤とを含有する消毒用組成物
 ・ 少なくとも抗ウイルス剤と保湿剤および/または化粧品用油脂類とを含有するローション、乳液またはクリーム
 洗浄用組成物は、食品、食器、調理器具、魚類等の飼育器具類や飼育水槽、作業者の手指や着衣などの汚れを落とすとともにエンベロープウイルスを消毒することができる態様の組成物であり、たとえば液状または固形状の洗剤として提供される。アルコール製剤および消毒用組成物は、食品、食器、調理器具、魚類等の飼育器具類や飼育水槽、作業者の手指、あるいは患者の汚物を取り扱った器具などに付着したエンベロープウイルスおよび細菌類を不活性化するために使用される態様の組成物であり、たとえば従来のエタノール製剤と同様の噴霧剤として提供される。これらの洗浄用組成物ないし消毒用組成物は、魚類等の卵、稚仔魚または親魚に感染したウイルスを消毒するための態様とすることもできる。ローション、クリームおよび乳液は、水仕事等で荒れやすい作業者の手指に塗ってスキンケアをするとともにエンベロープウイルスを消毒することができる態様の組成物(基礎化粧品)である。
-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.
 なお、本発明の抗ウイルス用組成物において、アルコール、界面活性剤、抗菌剤、保湿剤、および化粧品用油脂類は当然ながら2種以上を組み合わせて用いてもよい。たとえばアルコール製剤については、抗菌性をより高めるために脂肪酸エステル等の界面活性剤をさらに配合することも好ましい。また、上記洗浄用組成物は、界面活性剤に加えて抗菌剤やアルコールを配合したハンドソープなどの態様をとることができ、上記クリームは、手肌を保護する成分と共に手肌を清浄に保つための抗菌剤やアルコールを配合した態様をとることができる。 In addition, in the antiviral composition of the present invention, the alcohol, surfactant, antibacterial agent, moisturizing agent, 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.
 さらに、本発明の抗ウイルス用組成物には、本明細書中で具体的に説明している成分以外にも、所望の性能を賦与し各組成物の品質を高めるための各種成分、たとえば増粘剤(キサンタンガム、ローカストビーンガム、ポリアクリル酸ナトリウム等)、酸化防止剤、香料、色素など、またローション等の化粧品にあっては肌荒れ防止剤、消炎剤などを、適宜配合することができる。 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.
  ・抗ウイルス剤の含有量
 本発明の抗ウイルス用組成物における抗ウイルス剤の含有量は、エンベロープウイルスに対する抗ウイルス性が発現される範囲において、組成物の成分構成や使用方法等の態様に応じて適宜調整することができるが、抗ウイルス剤、より具体的には抗ウイルス剤中のカキ抽出物などの有効成分が、抗ウイルス用組成物全体に対して好ましくは0.01~5重量%、より好ましくは0.1~2重量%となるような量にすればよい。
-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 based on the whole antiviral composition. More preferably, the amount may be 0.1 to 2% by weight.
 なお、上記の抗ウイルス剤の含有量は「固形分」に基づくものであり、柿の実の抽出液のような液状物を製造原料として用いる場合には、その液状物中の固形分(乾燥または凍結乾燥により得られる粉末)の重量が上記範囲内となるよう、液状物の配合量を調節すればよい。柿の実の搾汁には、通常5~10%程度の固形分が含有されている。 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. Persimmon fruit juice usually contains about 5-10% solids.
  ・ビタミンC類
 本発明の抗ウイルス用組成物には、上述した抗ウイルス剤に加えて、食品等に添加される酸化防止剤として知られているビタミンC類を配合することが好ましい。ここで「ビタミンC類」とは、一般的にビタミンCと呼ばれているL-アスコルビン酸のほか、DL-アスコルビン酸や、アスコルビン酸エステル(パルミチン酸エステルなど)などを含む総称である。ビタミンC類を配合することによりカキ抽出物(特にカキタンニン)の酸化が抑制され、ウイルスに対する効果が安定的、持続的に発揮されるようになり、あわせて酸化による赤色の発色を抑制することもできる。
-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 C” 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.
  ビタミンC類の添加量は、抗ウイルス用組成物全体(溶媒等を含む。)に対して、0.01~5.0重量%の割合が好ましく、0.05~2.0重量%の割合がより好ましい。 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.
  ・アルコール
 アルコールとしては、一般的なアルコール製剤と同様のものを用いることができるが、細菌類に対する優れた抗菌性を有し食品添加物としても認められているエタノールおよび/またはプロパノールが好ましい。これらのアルコールの濃度は一般的なアルコール製剤と同程度であればよく、抗菌性を考慮しながら調整することができるが、アルコール製剤全体に対して10~80%程度とすることが好ましい。なお、アルコールは溶剤としてアルコール製剤以外の組成物に用いられることもあり、また肌への収斂性や防腐性をもたらす成分として化粧品等に配合することもできる。
-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.
  ・界面活性剤
 界面活性剤には、カチオン系、アニオン系、両イオン系および非イオン系のものがあるが、カキ縮合型タンニン(ポリフェノール)などの化学的性質を考慮すると、本発明ではアニオン系界面活性剤および/または非イオン系界面活性剤を用いることが好ましい。
・ 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.
 アニオン系界面活性剤としては、たとえば、石けん(高級脂肪酸のアルカリ塩)、モノアルキル硫酸塩、アルキルポリオキシエチレン硫酸塩、アルキルベンゼンスルホン酸塩、モノアルキルリン酸塩などが挙げられる。 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.
 非イオン系界面活性剤としては、たとえば、ポリオキシエチレンアルキルエーテル、ポリオキシエチレン脂肪酸エステル、多価アルコール(グリセリン、糖アルコール等)の脂肪酸部分エステル、脂肪酸ジエタノールアミドなどが挙げられる。 Examples of nonionic surfactants include polyoxyethylene alkyl ethers, polyoxyethylene fatty acid esters, fatty acid partial esters of polyhydric alcohols (such as glycerin and sugar alcohol), and fatty acid diethanolamides.
 これらの界面活性剤のうち、グリセリン脂肪酸部分エステル、ソルビタン脂肪酸部分エステル、ショ糖脂肪酸部分エステルなど食品添加物として認められているものは、食品、食器、調理器具に付着しても問題にならない点で本発明における好ましい界面活性剤である。 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.
 なお、上記のような界面活性剤には細菌類の細胞膜やウイルスのエンベロープを破壊する作用もあり、たとえばグリセリンの炭素数6~18の脂肪酸(炭素数10のカプリン酸など)との部分エステルはエンベロープウイルスに対する抗ウイルス性および大腸菌や黄色ブドウ球菌に対する抗菌性に優れているため、前述の抗ウイルス剤に有効成分として、あるいはアルコール製剤などの組成物にこれらの界面活性剤を配合することも好適である。また、界面活性剤はクリームや乳液において油相と水相とを混和するための成分としても用いられる。 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.
  ・抗菌剤
 本発明で用いることのできる、前述のエタノール、クエン酸等の有機酸およびその塩以外の抗菌剤(殺菌剤、除菌剤とよばれる物質を含む。)は特に限定されるものではないが、公知の抗生物質や合成抗菌剤など、たとえば食品加工の際の感染あるいは院内感染が問題となる大腸菌、黄色ブドウ球菌、MRSA、サルモネラ、腸炎ビブリオ、緑膿菌などに対して有効であるものが好適である。なかでも、イソプロピルメチルフェノール、ブチルパラヒドロキシベンゾエート、トリクロサンなどの合成抗菌剤は、抗菌作用に優れている点およびカキ抽出物との相溶性の点で本発明における好ましい抗菌剤である。なお、上記のような抗菌剤として用いられる物質は、前述のエタノール製剤に配合してもよく、化粧品等において防腐剤として利用されることもある。
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.
  ・保湿剤
 本発明で用いることのできる保湿剤(湿潤剤)は、一般的なローション、乳液、クリーム等の化粧品に用いられているものと同様であり、たとえば、グリセリン、プロピレングリコール、ソルビトール、ポリエチレングリコール、ヒアルロン酸、コンドロイチン硫酸ナトリウム、セラミド、アロエエキスなどが挙げられる。これらの保湿剤のうち、アロエエキスなど食品または食品添加物として認められているものは、食品、食器、調理器具に付着しても問題にならない点で本発明における好ましい保湿剤である。
-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.
  ・化粧品用油脂類
 化粧品用油脂類は、皮膚面に被膜を形成して皮膚の保護や柔軟性、滑沢性の賦与などの役割を果たし、また化粧品に適度な使用感を持たせるための成分である。本発明では、一般的な乳液、クリーム等の化粧品に用いられているものと同様の化粧品用油脂類を用いることができ、たとえば下記のようなものが挙げられる。
・ 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.
 ・ 油脂(高級脂肪酸とグリセリンのエステル)…植物性油脂、動物性油脂またはこれらの水素添加物(部分水添ナタネ油等)、合成トリグリセリド(トリ(カプリル/カプリン酸)グリセリル等)など;
 ・ ロウ(高級脂肪酸と高級アルコールの常温で固体のエステル)…植物性ロウ、動物性ロウ(蜜蝋、ラノリン等)など;
 ・ 炭化水素…鉱物性炭化水素(流動パラフィン、ワセリン、パラフィン等)、動物性炭化水素(スクワラン等)など;
 ・ 高級脂肪酸…ラウリン酸、ミリスチン酸、パルミチン酸、ステアリン酸、オレイン酸、イソステアリン酸など;
 ・ 高級アルコール…セタノール、ステアリルアルコール、ラノリンアルコールなど;
 ・ エステル(ロウ類以外の、脂肪酸とアルコールとのエステル)…ミリスチン酸ミリスチル、ジオレイン酸プロピレングリコール、乳酸セチルなど。
・ 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.
 これらの化粧品用油脂類のうち、蜜蝋など食品または食品添加物として認められているものは、食品、食器、調理器具に付着しても問題にならない点で本発明における好ましい化粧品用油脂類である。 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. .
  ・製造方法
 本発明の抗ウイルス用組成物の製造方法は、製造原料の一つとして抗ウイルス剤(カキ抽出物)を配合し、必要に応じてさらにビタミンC類を配合し、これらのことにあわせて適宜調整を施すこと以外は、従来のアルコール製剤、洗浄剤、消毒剤、ローション、乳液、クリーム等の製造方法と同様である。すなわち、それらの従来品の一般的な(または必要に応じて微調整した)製造原料に加えて抗ウイルス剤を配合し、従来品と同様(または必要に応じて微調整した)製造工程により、本発明の抗ウイルス用組成物を製造することができる。たとえば、クリームの態様をとるのであれば、精製水に抗ウイルス剤やその他の成分を添加して水相部を調製し、一方で化粧品用油脂類などからなる油相部を調製し、これらを所定の割合で混合するようにして製造すればよい。
-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.
 また、本発明の抗ウイルス用組成物の使用方法も、従来のアルコール製剤、洗浄剤、消毒剤、ローション、乳液、クリーム等と同様である。さらに、たとえば洗浄剤であれば使用時に希釈して用いるような濃縮型のものにしたり、アルコール製剤や消毒剤であればスプレー型のほか、不織布に含浸させて拭き取り型のものにしたりするなど、本発明の抗ウイルス用組成物は使用方法に応じて適宜好ましい態様で製品化することもできる。 Also, the method of using the antiviral composition of the present invention is 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.
 なお、本発明の抗ウイルス剤または抗ウイルス用組成物に有機酸および/またはその塩を配合する場合は、それらの水溶液のpHが好ましくは5.0~2.0、より好ましくは4.8~2.0となる量で、さらに好ましくは4.0~2.0となる量の有機酸および/またはその塩を添加することが好適である。
- 医薬品等 -
 本発明の抗ウイルス剤は、エンベロープウイルスに起因する感染症の治療剤または予防剤の有効成分として使用することができる。このような医薬品の剤型は、たとえば液剤、シロップ剤、錠剤、カプセル剤、散剤、顆粒剤などの経口摂取型、あるいは注射剤といった中から適宜選択することができ、必要に応じて賦形剤(たとえば乳糖やその他の糖類)、結合材(たとえば澱粉、メチルセルロース、ポリビニルアルコール)、安定化剤(たとえばアスコルビン酸)、保存剤(たとえばパラオキシ安息香酸エステル)、甘味料、溶剤など各種の添加剤を併用し、一般的な製剤方法に従って製造することができる。また、これらの医薬品の有効投与量は、患者の年齢、体重、症状、薬剤の投与経路、投与スケジュール、製剤形態、素材の阻害活性の強さなどに応じて適宜決定することができ、医薬品中の抗ウイルス剤の含有量もそれらの条件に応じて調節すればよい。
When an organic acid and / or a salt thereof is added to the antiviral agent or antiviral composition of the present invention, the pH of the aqueous solution is preferably 5.0 to 2.0, more preferably 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.
 なお、本発明の抗ウイルス剤およびこれを含有する医薬品は、ヒトに対して投与する態様のみならず、ほ乳類や魚類などエンベロープウイルスが感染しうるヒト以外の動物に対して投与する態様をもとりうる。たとえば魚類については、抗ウイルス剤ないしこれを含有する医薬品を餌料に混合して経口投与することができるほか、注射器などを用いて強制的に経口投与する方法や、飼育水に抗ウイルス剤を添加して一定時間あるいは常時魚を飼う“薬浴”などの方法をとることもできる。 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.
 さらに、本発明の抗ウイルス剤は、たとえば適度な濃度になるよう水で希釈した上でうがい液または口腔用スプレーとして用いてもよく、用途は特に限定されるものではない。 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 to an appropriate concentration, and its use is not particularly limited.
 [実施例1]
 表2に示す配合組成に従った薬剤を調製し、ヒト型インフルエンザウイルス、トリ型インフルエンザウイルス、水疱性口内炎ウイルスについてはそのまま、単純ヘルペスウイルス1型およびニューカッスル病ウイルスについてはさらに水で半分に希釈して、以下の実施例に用いた。対照としてはリン酸緩衝生理食塩水(PBS)を用いた。なお、柿渋FD末(カキ抽出物)は、十分に殺菌(NaClO)、洗浄、変色防止(ビタミンC)等の処理をした、蔕を切除した柿の未成熟果をダイス状にカットして潰し、得られた果実・果汁溶液を200メッシュ篩にかけ、遠心分離し、高温殺菌処理(120~130℃、7~10秒)をした後、フリーズドライ処理をして調製したものを用いた。
[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 (120 to 130 ° C., 7 to 10 seconds), and then freeze-dried and used.
Figure JPOXMLDOC01-appb-T000008
Figure JPOXMLDOC01-appb-T000008
Figure JPOXMLDOC01-appb-T000009
Figure JPOXMLDOC01-appb-T000009
 上記表3に示した試験ウイルスそれぞれのウイルス液と、上記表2に示した薬剤または対照それぞれとを当量ずつ(各35μL)混和して、室温で3分間反応させた後、DMEM (Sulbecco's modified minimun essential medium)で10倍段階希釈列を調製した。希釈したウイルス液を96穴プレートの単層培養細胞に接種し(100μL/well)、培養した。4日後以降にCPEが広がったところで固定・染色し、Behrens-Kaerber法を用いて50%感染量(単位:50% tissue culture infections dose [TCID50])を算出し、ウイルス感染価を測定した。結果は表4および図1~5に示す通りである。 The virus solution of each test virus shown in Table 3 above and each 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 DMEMD (Sulbecco's modified minimun Essential dilution medium) was used to prepare a 10-fold serial dilution series. 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, and the Behrens-Kaerber method was used to calculate the 50% infectious dose (unit: 50% tissue culture infections dose [TCID50]), and the virus infectivity titer was measured. The results are as shown in Table 4 and FIGS.
Figure JPOXMLDOC01-appb-T000010
Figure JPOXMLDOC01-appb-T000010
 上記5種類のウイルスはいずれも、20%または10%(w/w)エタノールではほとんど影響を受けない一方、さらに柿渋FD末、ワットルタンニン、または緑茶タンニンを配合した場合に感染価が大きく低下し、抗ウイルス活性が確認された。この結果は、これらの物質がそれぞれが単独で、広範なエンベロープウイルスに対する優れた有効成分となることを示している。 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.
 また、ペンタガロイルグルコースは、水疱性口内炎ウイルスに対してはやや弱いものの、各ウイルスに対する抗ウイルス活性が確認された。ピロガロールも、ニューカッスル病ウイルスを除く4種のウイルスに対する抗ウイルス活性が確認された。さらに、グリセリンモノカプレートは上記5種のウイルス全てに対して、クエン酸・クエン酸三ナトリウムはニューカッスル病ウイルスを除く4種のウイルスに対して、抗ウイルス活性が確認された。 Moreover, although pentagalloylglucose 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.
 一方、コーヒータンニンについては、上記5種のいずれのウイルスに対しても抗ウイルス活性をほとんど示さなかった。プロピルガレートは、ウイルスの種類によって多少の抗ウイルス活性を示した。 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.
 [実施例2]
 ウイルス性出血性敗血症ウイルス(VHSV)は、マス類に出血性敗血症をもたらすが、近年ヒラメ等でも本病が確認されている(Takano et al., 2001)。
[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).
 被検試薬を表5に示す。各被検試薬は、Hanks' balanced salt solution (日水)(HBSS)を用いて0.2%の濃度に調整した。その試薬50 μLに対し、各種ウイルス液50 μLを混合し(試薬終濃度0.1%)、常温で2分間静置した。その後、9.9 mLのHBSSを加えて反応を止め、さらにこれらサンプルの10倍の希釈系列をHBSSを用いて作製した。 The test reagents are shown in Table 5. 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 HBSS, and a 10-fold dilution series of these samples was prepared using HBSS.
Figure JPOXMLDOC01-appb-T000011
Figure JPOXMLDOC01-appb-T000011
 ウイルス力価測定試験は、まずFHM魚類培養細胞(Pimephales promelas由来)を96穴プレート(IWAKI)に80% confluentとなるように播き、培地を各wellに90 μLずつ加えて24時間培養した。なお、培地はMEMを使用した。その後、先に作製した希釈系列液を各wellに10 μLずつ接種し、さらに10日間培養を行って細胞変性効果(ウイルス感染の指標)の出現を確認した。細胞変性効果が見られなくなる限界希釈点を確認し、Reed and Muench (1938)の方法に従ってウイルス力価を測定した。コントロール区のウイルス力価(100%)に対する試験区のウイルス力価の割合を計算し、抗ウイルス活性を評価した(表6)。 In the virus titer measurement test, first, FHM fish cultured cells (derived from Pimephales® promelas) were 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 solution 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).
Figure JPOXMLDOC01-appb-T000012
Figure JPOXMLDOC01-appb-T000012
 ウイルス性出血性敗血症ウイルスに対しては、発酵柿渋液(カキ抽出物)、ペンタガロイルグルコース、ワットルタンニン、緑茶タンニン(カテキン類)、ピロガロールが高い効果を示し、これらが優れた有効成分となりうることが示されている。また、没食子酸、五倍子タンニンもこれらに近い効果を示し、コーヒータンニンも一定の効果を示した。 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.
 [実施例3]
 以下の成分を撹拌混合することにより、エタノール製剤、手洗いフォーム剤およびハンドローションを調製することができた。
[Example 3]
By mixing the following ingredients with stirring, an ethanol preparation, a hand-washing foam and a hand lotion could be prepared.
 エタノール製剤(HA-72A):柿渋FD末0.3重量部/エタノール50重量部/クエン酸1.6重量部/クエン酸三ナトリウム0.5%重量部/グリセリンモノカプレート0.5重量部/水(残部)。 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).
 エタノール製剤:柿渋FD末0.3重量部/エタノール50重量部/クエン酸1.6重量部/クエン酸三ナトリウム0.5重量部/グリセリンモノカプレート0.5重量部/ビタミンC0.5%重量部/水(残部)。 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).
 手洗いフォーム剤:イソプロピルメチルフェノール0.1重量部/柿渋FD末0.5重量部/95%エタノール20重量部/マイドール12(花王(株)製。ラウリルグルコシド)7.0重量部/グリセリン15.0重量部/クエン酸1.0重量部/グリセリンモノカプレート0.3重量部/精製水56.1重量部。 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.
 手洗いフォーム剤(KSF15-2):イソプロピルメチルフェノール0.1重量部/柿渋FD末0.5重量部/95%エタノール18重量部/マイドール12(花王(株)製。ラウリルグルコシド)7.0重量部/グリセリン15.0重量部/クエン酸1.0重量部/グリセリンモノカプレート0.3重量部/精製水58.1重量部。 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.
 ハンドローション:アラントイン0.1重量部/グリチルリチン酸二カリウム0.1重量部/柿渋FD末0.3重量部/95%エタノール54.0重量部/グリセリン2.0重量部/クエン酸0.7重量部/クエン酸三ナトリウム0.3重量部/グリセリンモノカプレート0.3重量部/精製水42.0重量部。 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.
 [実施例4]
  (1)使用薬剤
 実施例3に従って調製されたHA-72AおよびKSF15-2、および対照としてリン酸緩衝生理食塩水(PBS)
  (2)使用ウイルス
 鳥インフルエンザウイルス A/swan/Shimane/499/83(H5N3)
  (3)細胞
 MDCK(+) cells
(イヌ腎尿細管上皮細胞由来:Noma K et al. Arch. Virol. 143:1893-1909, 1998.)
  (4)ウイルス感染価測定法
 ウイルス液と薬剤を等量ずつ(各35μL)混和して、室温で3 分間反応させたのち、DMEM (Dulbecco's modified minimum essential medium)で10 倍段階希釈列を調製した。希釈したウイルス液を96 穴プレートの単層培養細胞に接種し(100μL/well)、培養した。4 日後以降にCPE が広がったところで固定・染色し、Behrens-Kaerber 法を用いて50%感染量(単位:50% tissue culture infectious dose[TCID50])を算出し、ウイルス感染価を測定した。
[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.
 処理時間の検討のためには、ウイルス液と薬剤を混合して、所定の時間(10, 30,60 秒)後にDMEM で500 倍に希釈して薬剤との反応を停止させ、同様に感染価を測定した。得られた感染価は500 倍にして補正した。 In order to examine the treatment time, the virus solution and the drug were mixed, and after a predetermined time (10, 30, 30 seconds), diluted with DMEM 500 times to stop the reaction with the drug. Was measured. The obtained infectious titer was corrected by multiplying by 500 tons.
  (5)結果
 薬剤の作用:
 HA-72AおよびKSF15-2ともに3分間の処理でウイルス活性が検出限界以下に低下した。両薬剤ともに細胞に対して、ある程度傷害性があるので、結果の「3.2E+03 TCID50/ml」というのはウイルスの作用が検出できる限界である。
(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.
Figure JPOXMLDOC01-appb-T000013
Figure JPOXMLDOC01-appb-T000013
 処理時間の効果:
 500 倍に希釈しているために1.6.E+04 TCID50/ml がウイルス活性の検出限界であるので、10 秒間の処理で、すでにウイルス活性が検出できないほど低下していると考えられる。以上、両試薬とも、鳥インフルエンザウイルスを検出できないほど不活化(約3000 倍以上)する。また、少なくとも10 秒の処理で有効であると考えられる。
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.
Figure JPOXMLDOC01-appb-T000014
Figure JPOXMLDOC01-appb-T000014
 [実施例5]
  (1)使用薬剤
 実施例3に従って調製されたHA-72AおよびKSF15-2、および対照としてリン酸緩衝生理食塩水(PBS)
  (2)使用ウイルスおよび細胞
[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
Figure JPOXMLDOC01-appb-T000015
Figure JPOXMLDOC01-appb-T000015
  (3)ウイルス感染価測定法
 ウイルス液と薬剤を等量ずつ(各35μL)混和して、室温で3分間反応させたのち、PBSで10倍段階希釈列を調製した。希釈したウイルス液を96穴プレートの単層培養細胞に接種し(50μL/well)、30分間ウイルス吸着を行った。その後、ウイルス接種液を吸引除去し、DMEM, 20μg/mlトリプシン(100μL/well)を加えた。6日後にCPEが広がったところで固定・染色し、Behrens-Kaerber法を用いて50%感染量(単位:50% tissue culture infectious dose [TCID50])を算出し、ウイルス感染価を測定した。
(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)結果および考察
 HA-72AおよびKSF15-2ともに、H1N1ウイルスを高度に不活化した。元のウイルスの感染価がそれほど高くなかったので、0.06%以下に抑制したという結果であるが、実際にはこれよりも高度に不活化している可能性がある。
(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.
Figure JPOXMLDOC01-appb-T000016
Figure JPOXMLDOC01-appb-T000016
 [実施例6]
  (1)水性搾汁液の製造法
 原料青柿(千葉産県百目柿,2009年8月22日採取)330gを洗浄乾燥し蔕を除去した後、約2センチ角に切断すると同時に種を取り除いた(280g)。これをミキサーに取り、L-アスコルビン酸(ビタミンC)2.8g(1%)と精製水280mlと共に約3分間かけて十分に粉砕した。これを不織布で数回に分けて搾り70~80℃で約30分加熱滅菌すると淡黄色液が得られた(460g)。この水性搾汁液(カキ抽出物処理物)を密閉容器に入れて常温に置いたところ、長期間(少なくとも3ヶ月間)、異臭、変色、沈殿を生じることなく保存可能であった。
[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 ground sufficiently with 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 sterilized by heating 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.
   柿果肉の糖度   9.4%(糖度計 ATAGO Pal-1)
   タンニン含有量  2.2%(定量法 Folin-Denis法)
  (2)エタノール性絞汁液の製造法
 原料青柿(千葉県産百目柿,2009年8月22日採取)300gを洗浄乾燥し蔕を除去した後、約2センチ角に切断すると同時に種を取り除いた(260g)。これをミキサーに取り、L-アスコルビン酸(ビタミンC)2.6g(1%)と95%エタノール260ml(210g)と共に約3分かれて十分に粉砕した。これを不織布で数回に分けて搾ると淡黄緑色液が得られた(430g)。このエタノール性搾汁液(カキ抽出物処理物)を密閉容器に入れて常温に置いたところ、長期間(少なくとも3ヶ月間)、異臭、変色、沈殿を生じることなく保存可能であった。
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 was 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.
   柿果肉の糖度   9.5%(糖度計 AYAGO Pal-1)
   タンニン含有量  2.4%(定量法 Folin-Denis法)
Sugar content 柿 9.5% (sugar content meter AYAGO Pal-1)
Tannin content 2.4% (Quantitative Folin-Denis method)

Claims (12)

  1.  タンニンを含有するカキノキ属(Diospyros)の植物の果実の搾汁または抽出液を加熱またはアルコールで処理することによりその中に含有されていた当該カキノキ属の植物に由来する酵素を失活させて得られた、カキ抽出物処理物を有効成分とする、エンベロープウイルスに対する抗ウイルス剤。 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 enveloped virus, comprising the processed oyster extract as an active ingredient.
  2.  前記カキ抽出物処理物が少なくとも縮合型タンニンを含有するものである、請求項1に記載の抗ウイルス剤。 The antiviral agent according to claim 1, wherein the processed product of oyster extract contains at least condensed tannin.
  3.  前記カキノキ属の植物がカキノキ(Diospyros kaki)である、請求項1または2に記載の抗ウイルス剤。 The antiviral agent according to claim 1 or 2, wherein the plant belonging to the genus Oyster is Diospyros kaki.
  4.  さらに、カテキン類、ワットルタンニン、ペンタガロイルグルコース、コーヒータンニン、ピロガロール、没食子酸、五倍子タンニン、および有機酸および/またはその塩(前記カキ抽出物処理物中のものを除く。)からなる群から選ばれた少なくとも1種を有効成分として含有する、請求項1~3のいずれかに記載の抗ウイルス剤。 Further, the group consisting of catechins, wattle tannins, pentagalloyl glucose, coffee tannins, pyrogallol, gallic acid, pentaploid tannins, and organic acids and / or their salts (except those in the processed oyster extract). The antiviral agent according to any one of claims 1 to 3, which contains at least one selected from the above as an active ingredient.
  5.  前記エンベロープウイルスとして、A型インフルエンザウイルス属、ベシクロウイルス属、単純ウイルス属、アビュラウイルス属、またはノビラブドウイルス属に属するエンベロープウイルスを対象とする、請求項1~4のいずれかに記載の抗ウイルス剤。 The envelope virus according to any one of claims 1 to 4, wherein the envelope virus belongs to an influenza virus genus, a vesiculovirus genus, a simple virus genus, an abular virus genus, or a nobilabdovirus genus. Antiviral agent.
  6.  前記エンベロープウイルスとして、ヒト型インフルエンザウイルス、トリ型インフルエンザウイルス、水疱性口内炎ウイルス、単純ヘルペスウイルス1型、ニューカッスル病ウイルス、またはウイルス性出血性敗血症ウイルスを対象とする、請求項5に記載の抗ウイルス剤。 The antiviral according to claim 5, wherein the enveloped 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. Agent.
  7.  少なくとも請求項1~6のいずれかに記載の抗ウイルス剤とアルコールとを含有する、抗ウイルス用アルコール製剤。 An antiviral alcohol preparation containing at least the antiviral agent according to any one of claims 1 to 6 and an alcohol.
  8.  少なくとも請求項1~6のいずれかに記載の抗ウイルス剤と界面活性剤とを含有する、抗ウイルス洗浄用組成物。 An antiviral cleaning composition comprising at least the antiviral agent according to any one of claims 1 to 6 and a surfactant.
  9.  少なくとも請求項1~6のいずれかに記載の抗ウイルス剤と抗菌剤(エタノール、有機酸およびその塩を除く。)とを含有する、抗ウイルス消毒用組成物。 An antiviral disinfecting composition comprising at least the antiviral agent according to any one of claims 1 to 6 and an antibacterial agent (excluding ethanol, organic acids and salts thereof).
  10.  前記抗ウイルス剤中のカキ抽出物処理物(固形分換算)を組成物全体に対して0.01~5重量%の割合で含有する、請求項7~9のいずれかに記載の抗ウイルス用組成物。 The antiviral agent according to any one of claims 7 to 9, comprising a processed product of oyster extract (converted to solid content) in the antiviral agent in a proportion of 0.01 to 5% by weight with respect to the whole composition. Composition.
  11.  有機酸および/またはその塩を組成物のpHが6.0~2.0となる量で含有する、請求項7~10のいずれかに記載の抗ウイルス用組成物。 The antiviral composition according to any one of claims 7 to 10, comprising 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.  さらにビタミンC類を含有する、請求項7~11のいずれかに記載の抗ウイルス用組成物。 The antiviral composition according to any one of claims 7 to 11, further comprising vitamin Cs.
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JP2013014568A (en) * 2011-07-06 2013-01-24 Georgia Health Sciences Univ Research Inst Inc Composition and method for treating herpes simplex virus
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US8603227B2 (en) 2009-10-16 2013-12-10 Woongjin Coway Co., Ltd. Composition for prevention of influenza viral infection comprising tannic acid, air filter comprising the same and air cleaning device comprising the filter
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