JP2009203160A - Antiviral and antibacterial agent - Google Patents

Antiviral and antibacterial agent Download PDF

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JP2009203160A
JP2009203160A JP2006145984A JP2006145984A JP2009203160A JP 2009203160 A JP2009203160 A JP 2009203160A JP 2006145984 A JP2006145984 A JP 2006145984A JP 2006145984 A JP2006145984 A JP 2006145984A JP 2009203160 A JP2009203160 A JP 2009203160A
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antiviral
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antibacterial agent
bacteria
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Saihatsu Ko
再発 洪
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/06—Fungi, e.g. yeasts
    • A61K36/062—Ascomycota
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    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
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    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
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    • A01N63/00—Biocides, pest repellants or attractants, or plant growth regulators containing microorganisms, viruses, microbial fungi, animals or substances produced by, or obtained from, microorganisms, viruses, microbial fungi or animals, e.g. enzymes or fermentates
    • A01N63/20—Bacteria; Substances produced thereby or obtained therefrom
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
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    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
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    • A01N63/00—Biocides, pest repellants or attractants, or plant growth regulators containing microorganisms, viruses, microbial fungi, animals or substances produced by, or obtained from, microorganisms, viruses, microbial fungi or animals, e.g. enzymes or fermentates
    • A01N63/30—Microbial fungi; Substances produced thereby or obtained therefrom
    • A01N63/32—Yeast
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K20/00—Accessory food factors for animal feeding-stuffs
    • A23K20/10—Organic substances
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K20/00—Accessory food factors for animal feeding-stuffs
    • A23K20/10—Organic substances
    • A23K20/163—Sugars; Polysaccharides
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K50/00—Feeding-stuffs specially adapted for particular animals
    • A23K50/10—Feeding-stuffs specially adapted for particular animals for ruminants
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K50/00—Feeding-stuffs specially adapted for particular animals
    • A23K50/70—Feeding-stuffs specially adapted for particular animals for birds
    • A23K50/75—Feeding-stuffs specially adapted for particular animals for birds for poultry
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K50/00—Feeding-stuffs specially adapted for particular animals
    • A23K50/80—Feeding-stuffs specially adapted for particular animals for aquatic animals, e.g. fish, crustaceans or molluscs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/06—Aluminium, calcium or magnesium; Compounds thereof, e.g. clay
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/66—Microorganisms or materials therefrom
    • A61K35/74—Bacteria
    • A61K35/741—Probiotics
    • A61K35/742—Spore-forming bacteria, e.g. Bacillus coagulans, Bacillus subtilis, clostridium or Lactobacillus sporogenes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/66—Microorganisms or materials therefrom
    • A61K35/74—Bacteria
    • A61K35/741—Probiotics
    • A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/66—Microorganisms or materials therefrom
    • A61K35/74—Bacteria
    • A61K35/741—Probiotics
    • A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
    • A61K35/747—Lactobacilli, e.g. L. acidophilus or L. brevis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/06—Fungi, e.g. yeasts
    • A61K36/062—Ascomycota
    • A61K36/064—Saccharomycetales, e.g. baker's yeast
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C05—FERTILISERS; MANUFACTURE THEREOF
    • C05D—INORGANIC FERTILISERS NOT COVERED BY SUBCLASSES C05B, C05C; FERTILISERS PRODUCING CARBON DIOXIDE
    • C05D3/00—Calcareous fertilisers
    • C—CHEMISTRY; METALLURGY
    • C05—FERTILISERS; MANUFACTURE THEREOF
    • C05G—MIXTURES OF FERTILISERS COVERED INDIVIDUALLY BY DIFFERENT SUBCLASSES OF CLASS C05; MIXTURES OF ONE OR MORE FERTILISERS WITH MATERIALS NOT HAVING A SPECIFIC FERTILISING ACTIVITY, e.g. PESTICIDES, SOIL-CONDITIONERS, WETTING AGENTS; FERTILISERS CHARACTERISED BY THEIR FORM
    • C05G3/00—Mixtures of one or more fertilisers with additives not having a specially fertilising activity
    • C05G3/60—Biocides or preservatives, e.g. disinfectants, pesticides or herbicides; Pest repellants or attractants
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02E—REDUCTION OF GREENHOUSE GAS [GHG] EMISSIONS, RELATED TO ENERGY GENERATION, TRANSMISSION OR DISTRIBUTION
    • Y02E50/00—Technologies for the production of fuel of non-fossil origin
    • Y02E50/30—Fuel from waste, e.g. synthetic alcohol or diesel
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02W—CLIMATE CHANGE MITIGATION TECHNOLOGIES RELATED TO WASTEWATER TREATMENT OR WASTE MANAGEMENT
    • Y02W30/00—Technologies for solid waste management
    • Y02W30/40—Bio-organic fraction processing; Production of fertilisers from the organic fraction of waste or refuse

Abstract

<P>PROBLEM TO BE SOLVED: To provide a safe and inexpensive antiviral or antibacterial agent having an excellent antiviral or antibacterial activity for animals and plants, an anti-infection agent for poultry and livestock, a feed, a soil disease-controlling agent, a plant disease-controlling agent or a plant growth-controlling agent and an anti-infection agent for humans or the like, containing the same. <P>SOLUTION: This antiviral or antibacterial agent comprises polysaccharides originated from microorganisms including the microorganisms belonging to genera Bacillus, Lactobacillus, Streptococcus, Saccharomyces, Candida and Pichia and calcium sulfate as active ingredients. The anti-infection agent for the poultry and livestock, an anti-infection agent for pets, the feed, the soil disease-controlling agent, a fertilizer, the plant disease-controlling agent or the plant growth-controlling agent, an anti-infection agent for fishes and shellfishes, a controlling agent for aquaculture or the anti-infection agent for humans containing the above agent are also provided. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

本発明は、微生物由来の多糖類と硫酸カルシウムとを有効成分として含有する抗ウイルス又は抗菌剤に関し、より詳しくは、該多糖類は、微生物の生菌体及び／又は死菌体であることを含み、さらに、前記抗ウィルス又は抗菌剤を含有する家禽・家畜用感染防除剤、ペット用感染防除剤、飼料、土壌病害防除剤、肥料、植物病害防除剤又は植物生長調整剤、魚介類の感染防除剤、水産養殖用調整剤又はヒト用感染防除剤に関する。   The present invention relates to an antiviral or antibacterial agent containing a polysaccharide derived from a microorganism and calcium sulfate as active ingredients. More specifically, the polysaccharide is a living cell and / or a dead cell of a microorganism. In addition, an infection control agent for poultry and livestock, a pet infection control agent, a feed, a soil disease control agent, a fertilizer, a plant disease control agent or a plant growth regulator, and an infection of seafood The present invention relates to a control agent, an aquaculture preparation or a human infection control agent.

微生物を適当な培地で培養すると、液体培地を粘稠にしたり、寒天平板上で粘稠性のあるコロニーを形成する場合がある。このような現象は多くの場合、細胞外多糖体の生産によって起こる。これに対して、細菌細胞壁構成成分として細菌細胞表層の基礎構造をなしている多糖体がある。一方、種々のグラム陰性菌細胞壁にはリポ多糖体と呼ばれる多糖体が含まれている。リポ多糖体は抗原としての性質のほか、内毒素としての種々の生理活性を示すことが知られている。リポ多糖体に抗腫瘍作用のあることは古くから知られており、一時制癌剤として注目され活発な研究が行われた。しかし、リポ多糖体は腫瘍に出血壊死を起こし、縮小がみられるにもかかわらず、壊死周辺部分から再び腫瘍細胞が増殖してくるため、治療効果は低い。また、治癒効果を高めるリポ多糖体の投与を増すと、本来の毒性のため死亡率が高まるなど、制癌剤としての基体は未知の段階である。   When microorganisms are cultured in an appropriate medium, the liquid medium may become viscous or a viscous colony may be formed on an agar plate. Such a phenomenon is often caused by the production of extracellular polysaccharides. On the other hand, there is a polysaccharide that forms the basic structure of the bacterial cell surface layer as a component of the bacterial cell wall. On the other hand, various gram-negative bacterial cell walls contain polysaccharides called lipopolysaccharides. Lipopolysaccharides are known to exhibit various physiological activities as endotoxins in addition to their properties as antigens. It has been known for a long time that lipopolysaccharide has an antitumor effect, and has been actively studied as a temporary anticancer drug. However, lipopolysaccharide causes hemorrhagic necrosis in the tumor, and despite its shrinkage, the tumor cells proliferate again from the necrosis peripheral portion, and thus the therapeutic effect is low. In addition, when the administration of lipopolysaccharide that enhances the healing effect is increased, the mortality rate increases due to its inherent toxicity, and the substrate as an anticancer agent is at an unknown stage.

また、ムコ多糖は、本来、動物生体内多糖として見出され、ある種の生理活性を有し、その分布及び構造と機能について多くの研究が行われてきた。ムコ多糖を構成している主な糖成分は、一般的にアミノ酸とウロン酸であり、該ムコ多糖は、ヒアルロン酸に代表される非硫酸ムコ多糖と、コンドロイチン硫酸やヘパリンなど動物の生体内で重要な働きを担っていると考えられている硫酸ムコ多糖に大別される。特に後者の硫酸ムコ多糖は、種々の疾病によって質的及び量的に著しく変化する場合の多いことから病態生理学の分野で注目されてきた。そして、この種の硫酸ムコ多糖である、コンドロイチン硫酸、ヘパリン等が抗ウィルス作用が認められるに及んで、硫酸多糖全般の生理活性が見直されてきた。   In addition, mucopolysaccharides were originally found as animal in vivo polysaccharides and have certain physiological activities, and many studies have been conducted on their distribution, structure and function. The main sugar components that make up mucopolysaccharides are generally amino acids and uronic acids, which are non-sulfated mucopolysaccharides typified by hyaluronic acid, and in vivo in animals such as chondroitin sulfate and heparin. It is roughly divided into mucopolysulfate, which is thought to play an important role. In particular, the latter mucopolysaccharide sulfate has attracted attention in the field of pathophysiology because it often changes qualitatively and quantitatively due to various diseases. In addition, chondroitin sulfate, heparin, and the like, which are mucopolysulfates of this kind, have been reconsidered for their physiological activity as a result of their antiviral activity.

ある種の海洋微生物の菌体が多糖体を含み、これら多糖体を含む菌体が抗ウィルス、抗菌、抗腫瘍作用のあることが報告されている。例えば、ビブリオ（vibrio）ｓｐの多糖体、例えば、ビブリオ アルゴスス（vibrio algosus）の多糖体、ビブリオ アンギラルム（vibrio anguillrum）の多糖体、シュードモナス（pseudomonas）の多糖体、例えば、シュードモナス プトレフェクトマリナ（pseudomonas perfectomarina）の多糖体、その他硫酸多糖体を含む菌等がある。   It has been reported that the cells of certain marine microorganisms contain polysaccharides, and the cells containing these polysaccharides have antiviral, antibacterial and antitumor effects. For example, polysaccharides of vibrio sp, such as polysaccharides of vibrio algosus, polysaccharides of vibrio anguillrum, polysaccharides of pseudomonas, such as pseudomonas pseudomononas perfectomarina) and other bacteria containing sulfate polysaccharides.

また、多糖類の金属塩に抗ウィルス・抗菌活性があることが知られており、例えば、抗ウイルス活性を有するヘパリン亜鉛塩（例えば、特許文献１参照）、同じく抗ウイルス活性を有するデキストラン硫酸亜鉛塩（例えば、特許文献２参照）、病原菌に対する抗菌活性を有するヒアルロン酸重金属塩（例えば、特許文献３参照）や、クレブシエラ（Ｋｌｅｂｓｉｅｌｌａ）に属する微生物が生産する構成糖がＤ−グルクロン酸、Ｌ−ラムノース、Ｄ−ガラクトース及びＤ−グルコースの４種からなり、その構成モル比が、Ｄ−グルクロン酸：Ｌ−ラムノース：Ｄ−ガラクトース：Ｄ−グルコース＝０．８〜１．２ :２．４〜３．６ :０．８〜１．２ :０．８〜１．２である多糖類の抗菌性金属塩を有効成分とする抗ウイルス・菌剤（例えば、特許文献４参照）が知られている。   In addition, it is known that metal salts of polysaccharides have antiviral / antibacterial activity. For example, heparin zinc salt having antiviral activity (see, for example, Patent Document 1), zinc dextran sulfate having antiviral activity as well. Constituent sugars produced by microorganisms belonging to salts (for example, see Patent Document 2), hyaluronic acid heavy metal salts having antibacterial activity against pathogens (for example, see Patent Document 3), and microorganisms belonging to Klebsiella (D-glucuronic acid, L- It consists of four kinds of rhamnose, D-galactose and D-glucose, and the constituent molar ratio thereof is D-glucuronic acid: L-rhamnose: D-galactose: D-glucose = 0.8 to 1.2: 2.4 to 3.6: 0.8-1.2: An antiviral / bacterial agent containing an antibacterial metal salt of polysaccharide (0.8-1.2) as an active ingredient (for example, special Document 4 reference) are known.

さらに、サッカロミセス属に属する酵母から得られるマンナンからなる抗感染性物質（例えば、特許文献５参照）や、乳酸菌由来の多糖類には、薬理作用を有していることが多く、抗腫瘍剤として、或いは、これに関した文献も多数知られている（例えば、特許文献６、特許文献７、特許文献８参照）。   Furthermore, anti-infectious substances consisting of mannan obtained from yeast belonging to the genus Saccharomyces (see, for example, Patent Document 5) and polysaccharides derived from lactic acid bacteria often have a pharmacological action, and as antitumor agents Alternatively, many documents related to this are also known (see, for example, Patent Document 6, Patent Document 7, and Patent Document 8).

一方、硫酸カルシウムは、火力発電所における脱硫装置やリン酸製造の副産物として安価かつ大量に製造されており、製紙用填料、農業用土壌改良剤兼肥料等に幅広く使用され、その形態としてスラリー状として用いる場合に、水と微生物由来の多糖類（例えばアルカリゲネスレータスＢ−１６株菌）とを含む硫酸カルシウムスラリー組成物（例えば、特許文献９参照）が知られている。   Calcium sulfate, on the other hand, is manufactured at low cost and in large quantities as a by-product of desulfurization equipment and phosphoric acid production at thermal power plants, and is widely used in paper-making fillers, agricultural soil conditioners and fertilizers, etc. When used as a calcium sulfate slurry composition (for example, see Patent Document 9) containing water and a polysaccharide derived from a microorganism (for example, Alkaline Genestus B-16 strain).

特公昭６２−２５１２６号公報Japanese Examined Patent Publication No. 62-25126 特公昭６３−４８８４９号公報Japanese Examined Patent Publication No. 63-48849 特表昭６３−５０２６７０号公報JP-T 63-502670 特開平８−３３３２１４号公報JP-A-8-333214 特開昭５８−１０９４２３号公報JP 58-109423 A 特公昭６０−１８７７号公報Japanese Patent Publication No. 60-1877 特公平６−９６６０１号公報Japanese Examined Patent Publication No. 6-96601 特許第２６７８６７３号公報Japanese Patent No. 2678673 特開２００４−１９６５６４号公報JP 2004-196564 A

多糖類は、種々の微生物によって微生物細胞外（菌体外）へ分泌され、また細胞壁に存在しているが、得られる多糖類の性状は、基本的に微生物の種類に依存している。このように微生物由来の多糖類はその性状により、用途も異なり、粘性を有しているものは増粘物質としての用途がある。また、多糖類の薬理作用に注目した研究も活発に行われている。多糖類の中で、前述した、リポ多糖類はグラム陰性菌の細胞壁に存在し、ムコ多糖は、本来、動物生体内多糖として見出され、ある種の生理活性を有し、その分布及び構造と機能について多くの研究が行われてきた。ムコ多糖を構成している主な糖成分は、一般的にアミノ酸とウロン酸であり、該ムコ多糖は、ヒアルロン酸に代表される非硫酸ムコ多糖と、コンドロイチン硫酸やヘパリンなど動物の生体内で重要な働きを担っていると考えられている硫酸ムコ多糖に大別される。本発明の課題は、前述のリポ多糖類、硫酸多糖類等の有する生理活性作用に注目し、微生物が生産する多糖類又は該多糖類を含む生菌又は死菌体に、ある種の化合物と共に用いることで抗ウィルス・抗菌作用を有する物質とすることができ、該物質は動植物に対して、優れた抗ウイルス又は抗菌性能とを有し、安全で安価な抗ウイルス又は抗菌剤、前記抗ウィルス又は抗菌剤を含有する家禽・家畜用感染防除剤、ペット用感染防除剤、飼料、土壌病害防除剤、肥料、植物病害防除剤又は植物生長調整剤、魚介類の感染防除剤、水産養殖用調整剤又はヒト用感染防除剤を提供することにある。   Polysaccharides are secreted outside the microbial cells (outside the cells) by various microorganisms and are present in the cell wall, but the properties of the obtained polysaccharides basically depend on the type of microorganism. In this way, polysaccharides derived from microorganisms have different uses depending on their properties, and those having viscosity have uses as thickening substances. In addition, active research has been conducted focusing on the pharmacological action of polysaccharides. Among the polysaccharides, the above-mentioned lipopolysaccharide is present in the cell wall of Gram-negative bacteria, and mucopolysaccharide is originally found as an in vivo polysaccharide of the animal and has a certain physiological activity, its distribution and structure There has been a lot of research on function. The main sugar components that make up mucopolysaccharides are generally amino acids and uronic acids, which are non-sulfated mucopolysaccharides typified by hyaluronic acid, and in vivo in animals such as chondroitin sulfate and heparin. It is roughly divided into mucopolysulfate, which is thought to play an important role. An object of the present invention is to pay attention to the physiologically active action of the aforementioned lipopolysaccharide, sulfate polysaccharide, etc., and to produce a polysaccharide produced by a microorganism or a living or dead cell containing the polysaccharide together with certain compounds. It can be used as a substance having an antiviral / antibacterial action, and the substance has excellent antiviral or antibacterial performance against animals and plants, and is a safe and inexpensive antiviral or antibacterial agent. Or infection control agents for poultry and livestock containing antibacterial agents, infection control agents for pets, feed, soil disease control agents, fertilizers, plant disease control agents or plant growth control agents, fish and shellfish infection control agents, adjustment for aquaculture It is to provide an agent or a human infection control agent.

グラム陰性細菌の細胞壁に存在するリポ多糖類や海洋微生物の菌体が有するムコ多糖のような多糖類が抗ウィルス、抗病原菌、抗腫瘍作用を有するものの、自然の多糖体類は細菌からの分離、培養、毒性の確認及び該毒性の除去には困難を伴い、実用化が難しいことから、本発明者は、このような多糖類にある種の化合物を反応させることにより、抗ウィルス又は抗菌剤を得ようと鋭意検討した結果、安全性の高い微生物由来の多糖類及び硫酸カルシウム、或いはこのような多糖類を含む生菌又は死菌体と硫酸カルシウルムを含有させることで、優れた抗ウイルス又は抗菌剤が得られることを見出し、本発明を完成するに至った。   Although polysaccharides such as lipopolysaccharides present in the cell walls of gram-negative bacteria and mucopolysaccharides of the cells of marine microorganisms have antiviral, antipathogenic and antitumor effects, natural polysaccharides are separated from bacteria. Since the culture, confirmation of toxicity, and removal of the toxicity are difficult and difficult to put into practical use, the present inventor made an antiviral or antibacterial agent by reacting a certain compound with such a polysaccharide. As a result of earnest study to obtain a highly safe microorganism-derived polysaccharide and calcium sulfate, or by containing live or dead cells containing such polysaccharide and calcium sulfate sulfate, The present inventors have found that an antibacterial agent can be obtained and have completed the present invention.

すなわち本発明は、(１）バチルス（Bacillus）属、ラクトバチルス（Lactobacillus）属、ストレプトコッカス（Strptococcus）属、サッカロミセス（Saccharomyces）属、キャンディダ（Candida）属及びピキア（Pichia）属に属する微生物を含む微生物由来の多糖類と硫酸カルシウムとを有効成分として含有することを特徴とする抗ウイルス又は抗菌剤や、（２）微生物として、さらに、耐塩性酵母菌、耐塩性乳酸菌、硝化細菌、硫黄細菌、メタン酸化細菌、硫黄還元細菌、光合成細菌、好塩菌の群から選ばれる１種又は２種以上を用いることを特徴とする上記（１）記載の抗ウイルス又は抗菌剤や、（３）微生物由来の多糖類が、その生菌体及び／又は死菌体を含むことを特徴とする上記（１）又は（２）記載の抗ウイルス又は抗菌剤や、（４）さらに、藻類を含有することを特徴とする上記（１）〜（３）のいずれか記載のウイルス又は抗菌剤に関する。   That is, the present invention includes (1) microorganisms belonging to the genus Bacillus, the genus Lactobacillus, the genus Strptococcus, the genus Saccharomyces, the genus Candida, and the genus Pichia. An antiviral or antibacterial agent characterized by containing a polysaccharide derived from microorganisms and calcium sulfate as active ingredients; and (2) microorganisms, and further, salt-resistant yeast, salt-resistant lactic acid bacteria, nitrifying bacteria, sulfur bacteria, One or more selected from the group consisting of methane-oxidizing bacteria, sulfur-reducing bacteria, photosynthetic bacteria, and halophilic bacteria, or the antiviral or antibacterial agent according to (1) above, or (3) microorganism-derived The antiviral or antibacterial agent according to the above (1) or (2), wherein the polysaccharide comprises a living cell and / or dead cell, and (4) algae Characterized in that it contains about viruses or antimicrobial agent according to any one of the above (1) to (3).

また本発明は、（５）バチルス（Bacillus）属に属する微生物が、バチルス・ズブチルス（Bacillus subtilis）、バチルス・ナットウ（Bacillus natto）、バチルス・メガテリウム（Bacillus megaterium）の群から選ばれる１種又は２種以上であることを特徴とする上記（１）〜（４）のいずれか記載の抗ウイルス又は抗菌剤や、（６）ラクトバチルス（Lactobacillus）属に属する微生物が、ラクトバチルス・アシドフィラス（Lactobacillus acidophilus）、ラクトバチルス・プランタラム（Lactobacillus plantarum）、ラクトバチルス・ブレビス（Lactobacillus brevis）、ラクトバチルス・カゼイ（Lactobacillus casei）の群から選ばれる１種又は２種以上であることを特徴とする上記（１）〜（４）のいずれか記載の抗ウイルス又は抗菌剤や、（７）ストレプトコッカス（Streptococcus）属に属する微生物が、ストレプトコッカス・フェカリス（Streptococcus faecalis）、ストレプトコッカス・ラクティス（Streptococcus lactis）、ストレプトコッカス・サーモフィルス（Streptococcus thermophillus）の群から選ばれる１種又は２種以上であることを特徴とする上記（１）〜（４）のいずれか記載の抗ウイルス又は抗菌剤や、（８）サッカロミセス（Saccharomyces）属に属する微生物が、サッカロミセス・セレビシアエ（Saccharomyces cerevisiae）であることを特徴とする上記（１）〜（４）のいずれか記載の抗ウイルス又は抗菌剤や、（９）キャンディダ（Candida）属に属する酵母が、キャンディダ・ユーティリス（Candida utilis）であることを特徴とする上記（１）〜（４）のいずれか記載の抗ウイルス又は抗菌剤や、（１０）ピキア属に属する酵母が、ピキア・メンブラナエファシエンス（Pichia membranaefacience）であることを特徴とする上記（１）〜（４）のいずれか記載の抗ウイルス又は抗菌剤に関する。   In the present invention, (5) the microorganism belonging to the genus Bacillus is one or two selected from the group of Bacillus subtilis, Bacillus natto, and Bacillus megaterium. The antiviral or antibacterial agent according to any one of (1) to (4) above, or (6) a microorganism belonging to the genus Lactobacillus, wherein the microorganism belongs to the genus Lactobacillus acidophilus (Lactobacillus acidophilus) ), Lactobacillus plantarum, Lactobacillus brevis, Lactobacillus casei, or one or more selected from the group (1) ) To (4), or (7) Streptococcus genus The above-mentioned (1) characterized in that the microorganism to which the microorganism belongs is one or more selected from the group of Streptococcus faecalis, Streptococcus lactis, Streptococcus thermophillus. (4) The antiviral or antibacterial agent according to any one of (4) and (8) the microorganism belonging to the genus Saccharomyces is Saccharomyces cerevisiae (1) to (4) (9) The antiviral or antibacterial agent according to any one of (1) to (4) above, and (9) the yeast belonging to the genus Candida is Candida utilis. Or an antiviral or antibacterial agent according to any one of (10) and (10) a yeast belonging to the genus Pichia. Men bra seedling tumefaciens above (1) characterized in that it is a (Pichia Membranaefacience) relates to an anti-viral or antibacterial agent according to any one of to (4).

さらに本発明は、（１１）上記（１）〜（１０）記載のいずれかを含むことを特徴とする家禽・家畜用感染防除剤や、（１２）上記（１）〜（１０）記載のいずれかを含むことを特徴とするペット用感染防除剤や、（１３）上記（１）〜（１０）記載のいずれかを含むことを特徴とする飼料や、（１４）上記（１）〜（１０）記載のいずれかを含むことを特徴とする土壌病害防除剤や、（１５）上記（１）〜（１０）記載のいずれかを含むことを特徴とする肥料や、（１６）上記（１）〜（１０）記載のいずれかを含むことを特徴とする植物病害防除剤又は植物生長調整剤や、（１７）上記（１）〜（１０）記載のいずれかを含むことを特徴とする魚介類の感染防除剤や、（１８）上記（１）〜（１０）記載のいずれかを含むことを特徴とする水産養殖用餌や、（１９）上記（１）〜（１０）記載のいずれかを含むことを特徴とするヒト用感染防除剤に関する。   Furthermore, the present invention includes (11) a poultry / livestock infection control agent comprising any one of (1) to (10), and (12) any of (1) to (10). Or (13) feeds characterized by containing any one of the above (1) to (10), and (14) the above (1) to (10) ) A soil disease control agent characterized by containing any of the above, (15) a fertilizer characterized by containing any of the above (1) to (10), and (16) the above (1) A plant disease control agent or plant growth regulator characterized by containing any one of (10), or (17) a fish or shellfish containing any one of (1) to (10) above And (18) any one of (1) to (10) described above. And bait aquaculture, relates (19) above (1) to (10) for humans infected controlling agent characterized by comprising any description.

本発明の抗ウィルス又は抗菌剤は、優れた抗ウイルス又は抗菌性能とを有し、安全で安価な抗ウイルス又は抗菌剤とすること、及びこれらの製剤を含む、優れた抗ウイルス又は抗菌性能とを有する家禽・家畜用感染防除剤、ペット用感染防除剤、飼料、土壌病害防除剤、肥料、植物病害防除剤又は植物生長調整剤、魚介類の感染防除剤、水産養殖用調整剤又はヒト用感染防除剤を得ることができる。   The antiviral or antibacterial agent of the present invention has an excellent antiviral or antibacterial performance, and is a safe and inexpensive antiviral or antibacterial agent. Poultry and livestock infection control agent, pet infection control agent, feed, soil disease control agent, fertilizer, plant disease control agent or plant growth control agent, fish and shellfish infection control agent, aquaculture control agent or human An infection control agent can be obtained.

本発明の抗ウイルス又は抗菌剤としては、微生物由来の多糖類（オリゴ糖を含む）と硫酸カルシウムを有効成分とするものであれば特に制限されるものではなく、糖類としては、フコース、グルコース、ガラクトース、マンノース、アラビノース、キシロース、マジュロース、グルクロン酸及びラムノースを構成単糖として含むリポ多糖類、ムコ多糖類、これらの多糖類を糖鎖と有するペプチドグリカン複合体等又はこれらの１種又は２種以上、これらのオリゴ糖を含む多糖類からなる糖類を挙げることができる。   The antiviral or antibacterial agent of the present invention is not particularly limited as long as it contains microorganism-derived polysaccharides (including oligosaccharides) and calcium sulfate as active ingredients. Examples of sugars include fucose, glucose, Lipopolysaccharides, mucopolysaccharides containing galactose, mannose, arabinose, xylose, majurose, glucuronic acid and rhamnose as constituent monosaccharides, peptidoglycan complexes having these polysaccharides as sugar chains, etc., or one or more of these And saccharides composed of polysaccharides containing these oligosaccharides.

硫酸カルシウムとしては、天然のものである無水物、半水和物、二水和物のいずれも使用でき、天然の鉱物石膏及び塩田から集積された石膏等、また、火力発電所における脱硫装置やリン酸製造の副産物として安価かつ大量に製造されているものも使用することができる。   As calcium sulfate, any of natural anhydrides, hemihydrates and dihydrates can be used, natural mineral gypsum and gypsum accumulated from salt fields, etc., and desulfurization equipment in thermal power plants What is cheaply manufactured in large quantities as a by-product of phosphoric acid manufacture can also be used.

本発明の微生物由来の多糖類としては、微生物の生菌体及び／又は死菌体を含むものを用いてもよく、その微生物としては、多糖類（以下、オリゴ糖を含む）を生産することができる、又は細胞壁に多糖類を含む微生物であれば、特に制限されるものではない。例えば、リポ多糖類などの多糖類を生産又は細胞壁等に含む微生物として、バチルス（Bacillus）属、ラクトバチルス（Lactobacillus）属（乳酸菌）、ストレプトコッカス（Streptococcus）属（連球菌）、サッカロミセス（Saccharomyces）属（ビール酵母）、キャンディダ（Candida）属（トルラ酵母）、ピキア（Pichia）属に属する微生物や、オリゴ糖類を生産又は細胞壁に含む耐塩性酵母菌、耐塩性乳酸菌が挙げられ、その他、硝化細菌、硫黄細菌、メタン酸化細菌、硫黄還元細菌、光合成細菌等を挙げることができる。   As the polysaccharide derived from the microorganism of the present invention, one containing a living microbial cell and / or a dead cell of a microorganism may be used, and as the microorganism, a polysaccharide (hereinafter, including an oligosaccharide) is produced. The microorganism is not particularly limited as long as it is a microorganism capable of producing or containing a polysaccharide in the cell wall. For example, microorganisms that produce polysaccharides such as lipopolysaccharide or contain cell walls and the like include the genus Bacillus, the genus Lactobacillus (lactic acid bacteria), the genus Streptococcus (streptococcus), and the genus Saccharomyces. (Beer yeast), microorganisms belonging to the genus Candida (torula yeast), Pichia, salt-resistant yeasts that produce oligosaccharides or contain cell walls, salt-resistant lactic acid bacteria, and other nitrifying bacteria , Sulfur bacteria, methane oxidizing bacteria, sulfur reducing bacteria, photosynthetic bacteria, and the like.

本発明に係るバチルス（Bacillus）属として、枯草菌（B.subtilis）、納豆菌（B.nattou）、巨大菌（B.megaterium）を挙げることができる。   Examples of the genus Bacillus according to the present invention include Bacillus subtilis, B. nattou, and B. megaterium.

本発明に係るラクトバチルス属（Lactobacillus）に属する菌としては、ラクトバチルス・アシドフィラス（L.acidophilus）、ラクトバチルス・プランタリム（L. plantarum）、ラクトバチルス・ブレビス（L.brevis）、ラクトバチルス・カセイ（L.casei）、ラクトバチルス・デルブリッキ（L. delbriickii）、ラクトバチルス・ヘルベティカス（L.helveticus）又はラクトバチルス・ペントサス（L. pentosus）を挙げることはできる。   As a bacterium belonging to the genus Lactobacillus according to the present invention, Lactobacillus acidophilus (L. acidophilus), Lactobacillus plantarum (L. plantarum), Lactobacillus brevis (L. brevis), Lactobacillus Mention may be made of L. casei, L. delbriickii, L. helveticus or L. pentosus.

本発明に係るストレプトコッカス（Strptococcus）属に属する菌としては、ストレプトコッカス・フェカリス（S.faecalis）、ストレプトコッカス・ラクティス（S.lactis）、ストレプトコッカス・サーモフィルス（S. thermophilus）を挙げることができる。   Examples of the bacteria belonging to the genus Strptococcus according to the present invention include Streptococcus faecalis, S. lactis, and Streptococcus thermophilus.

本発明に係るサッカロミセス（Saccharomyces）属に属する菌としては、サッカロミセス・セレビシアエ（S. cerevisiae）を挙げることができる。   Examples of bacteria belonging to the genus Saccharomyces according to the present invention include S. cerevisiae.

本発明に係るキャンディダ（Candida）属は、キャンディダ・ユーティリス（C.utillis）、キャンディダ アルビカンス（C.albicans）、キャンディダ・リポリチカ（C.lipolytica）、キャンディダ・トロピカリス（C.tropicalis）を代表的なものとして挙げることができるが、その他、C.albicans var.stellatoidea, C.catenulata,Candida curvata, C. famata, C.glabrata, C.guilliermondii, C.humicola, C.intermedia, C. kefyr, C. krusei, C.loxderi, C. macedoniensis, C.magnoliae, C.maltosa, C. melinii, C. nitratophila, C.parapsilosis, C.pelliculosa, C.pintolopesii, C. pinus, C.pulcherrima, C.robusta, C.rugosa, C.zeylanoidesを挙げることができる。   The genus Candida according to the present invention includes C. utillis, C. albicans, C. lipolytica, and C. tropicalis. tropicalis) can be cited as typical examples, but C. albicans var.stellatoidea, C.catenulata, Candida curvata, C. famata, C.glabrata, C.guilliermondii, C.humicola, C.intermedia, C. kefyr, C. krusei, C. loxderi, C. macedoniensis, C. magnoliae, C. maltosa, C. melinii, C. nitratophila, C. parapsilosis, C. pelliculosa, C. pintolopesii, C. pinus, C. pulcherrima, C.robusta, C.rugosa, C.zeylanoides.

ピキア（Pichia）属に属する菌は、耐塩性酵母菌であり、有胞子酵母（Endomycetaceae科）の一属で、細胞は卵円形ないし円筒形で多極性出芽増殖する。大部分の種類は仮性菌糸を形成し、真正菌糸はごく少数にみられる。胞子はハンゼヌラ（Hansenura）と同様に球形、山高帽子形、土星形を示す。含糖液の表面にしばしば皮膜を形成しない種類もあり、硝酸塩は資化しない。ピキア・ファリノサ（Pichia farinosa）、ピキア・メンブラナエファシエンス（Pichia membranaefacience）が好ましく、その他、Pichia fermentans、Pichia pinus、Pichia subpelliculosaを挙げることができる。   The bacterium belonging to the genus Pichia is a salt-tolerant yeast and belongs to the spore yeast (Endomycetaceae family), and the cells are ovary or cylindrical and multipolar budding and proliferating. Most types form pseudohyphae and very few true hyphae. Spores, like Hansenura, are spherical, bowler hat, and Saturn. Some types often do not form a film on the surface of the sugar-containing liquid, and nitrates are not assimilated. Pichia farinosa and Pichia membranaefacience are preferable, and other examples include Pichia fermentans, Pichia pinus, and Pichia subpelliculosa.

本発明では、オリゴ糖類を生産又は細胞壁に含む耐塩性酵母菌や、耐塩性乳酸菌を用いることができる。耐塩性酵母菌として、サッカロミセス・ロキシ（S.rouxii）を、耐塩性乳酸菌として、ペディオコッカス・ハロフィラス（P.halophilus）を挙げることができる。   In the present invention, a salt-resistant yeast or a salt-resistant lactic acid bacterium that produces an oligosaccharide or contains a cell wall can be used. Examples of the salt-tolerant yeast include S. rouxii, and examples of the salt-tolerant lactic acid bacterium include P. halophilus.

硝化細菌として、ニトロバクタ−属、ニトロソモナス属を挙げることができ、たとえば、Nitrobacter winogradskyi、Nitrobacter agile、Nitrosomonas europaea、Nitrosomonas monocellaを挙げることができる。   Examples of nitrifying bacteria include the genus Nitrobacter and the genus Nitrosomonas, such as Nitrobacter winogradskyi, Nitrobacter agile, Nitrosomonas europaea, and Nitrosomonas monocella.

硫黄細菌として、Thiobacillus属、Thiobacterium属、Macromonas属、Thiovulum属、Thiospira属に属する菌を挙げることができる。   Examples of sulfur bacteria include bacteria belonging to the genera Thiobacillus, Thiobacterium, Macromonas, Thiovulum, and Thiospira.

メタン酸化細菌として、Methylococcus属、Methylomonas属に属する菌をを挙げることができる。   Examples of the methane oxidizing bacteria include bacteria belonging to the genus Methylococcus and the genus Methylomonas.

硫黄還元細菌として、Desulfovibrio属に属する菌を挙げることができる。   Examples of sulfur-reducing bacteria include bacteria belonging to the genus Desulfovibrio.

光合成細菌として、いわゆるphotosynthetic bacteriaに属する菌を挙げることができる。   Examples of photosynthetic bacteria include bacteria belonging to so-called photosynthetic bacteria.

本発明に係る微生物には、細胞表層にオリゴ糖を含有する好塩菌、例えば、Halococcus属球菌、Halobacterium属桿菌、Haloarcula属、Haloferax属、Natronobacterim属、Natronococcus属に属する菌を挙げることができる。   Examples of the microorganism according to the present invention include halophilic bacteria containing oligosaccharides on the cell surface, for example, bacteria belonging to the genus Halococcus spp., Halobacterium spp., Haloarcula spp., Haloferax spp., Natronobacterim spp.

本発明では、藻類として、藍藻等を、例えば、Calothrix scopulorum、Nostoc sp.、Anabaena cylindrica、Anabaena flos-aquae、Tolypothrix tenuisやChlorella vulgaris、Chlorella pyrenoidosa、Chlorella ellipsoida、Ulothrix sp.、Uronema gigas、Spirulina maxima等を用いることができる。   In the present invention, as algae, cyanobacteria and the like, for example, Calothrix scopulorum, Nostoc sp., Anabaena cylindrica, Anabaena flos-aquae, Tolypothrix tenuis and Chlorella vulgaris, Chlorella pyrenoidosa, Chlorella ellipsoida, Ulothrix sp. Can be used.

本発明は、微生物を培養後、多糖類を微生物から分離して用いてもよいが、分離せずに生菌が混入したものを用いることもでき、取扱上、生菌体を含む多糖類混合物を用いることが好ましい。多糖類と硫酸カルシウムとの配合割合は、１〜９：９〜１の割合で用いることができ、好ましくは、１：１の割合で混合する（以下、このように配合した本発明の製品を「Ａ剤製品」（総菌数１×１０３以上）という場合がある）。 In the present invention, after culturing the microorganism, the polysaccharide may be used after being separated from the microorganism, but it is also possible to use a mixture of living bacteria without separation. Is preferably used. The blending ratio of the polysaccharide and calcium sulfate can be used in a ratio of 1-9: 9-1, preferably mixed in a ratio of 1: 1 (hereinafter, the product of the present invention blended in this way “A product” (sometimes more than 1 × 10 3 total bacteria)).

家禽・家畜用感染防除剤として、飼料に配合するには、飼料総重量に対し０．３〜０．５％配合することが好ましい（飼料１０００ｋｇ：Ａ剤３〜５ｋｇ）。   As a poultry / livestock infection control agent, it is preferable to add 0.3 to 0.5% based on the total weight of the feed (feed 1000 kg: A agent 3 to 5 kg).

ペット用の抗ウィルス又は抗菌剤として、餌に配合するには、餌総重量に対して０．３〜０．５％配合することが好ましい（餌１０ｋｇ：Ａ剤３０〜５０ｇ）。   As an antiviral or antibacterial agent for pets, it is preferable to add 0.3 to 0.5% based on the total weight of the feed (10 kg of feed: 30 to 50 g of agent A).

魚介類の感染防除剤として、餌に配合するには、餌総重量に対して０．５〜１％配合することが好ましい（餌１０００ｋｇ：Ａ剤５〜１０ｋｇ）。また、養殖池に散布する場合は、２００〜３００ｋｇ／ｈａ／回で、月１〜２回散布することが好ましい。   In order to mix into a bait as a fish and shellfish infection control agent, it is preferable to mix 0.5 to 1% of the total weight of the bait (1000 kg of feed: 5 to 10 kg of agent A). Moreover, when spraying to an aquaculture pond, it is preferable to spray 200 to 300 kg / ha / time and once or twice a month.

土壌病害防除剤として散布する場合、３００〜５００ｋｇ／ｈａ／回で、Ａ剤製品を直接農地に散布する。肥料に混合して用いる場合は、肥料：Ａ剤を１：１の割合で混合して使用する。   When spraying as a soil disease control agent, the agent A product is sprayed directly onto farmland at 300 to 500 kg / ha / time. When mixed with fertilizer and used, fertilizer: Agent A is mixed and used at a ratio of 1: 1.

ヒトに用いる場合は、飲食品総重量に対して０．３〜０．５％配合することが好ましい。   When used for humans, it is preferable to blend 0.3 to 0.5% with respect to the total weight of the food and drink.

本発明の、抗ウイルス又は抗菌剤とは、ヒト又は家禽・家畜がウィルス又は菌により感染した場合の感染症に対する予防及び／又は治療を意味する。感染症の種類としては、ヒト、家畜・家禽類及び魚介類により様々であるが、微生物が生体宿主に侵入し定着、増殖する病気の全てをいう。本発明の抗ウィルス又は抗菌剤は、感染症の中でも消化器系の感染症の予防及び治療に効果がある。特に家畜についてみると、家畜が感染しやすい病原菌として、サルモネラ、クロストリディウム、浮腫病を引き起こす大腸菌や腸管毒血症性大腸菌等の大腸菌を挙げることができ、これらの病原菌の感染に対して抗菌作用を有する。   The antiviral or antibacterial agent of the present invention means prevention and / or treatment for infectious diseases when humans or poultry / livestock are infected by viruses or fungi. There are various types of infectious diseases depending on humans, livestock / poultry and fish and shellfish, but all diseases in which microorganisms invade a living host, settle and proliferate. The antiviral or antibacterial agent of the present invention is effective in preventing and treating digestive system infections among infectious diseases. Especially regarding livestock, Salmonella, Clostridium, Escherichia coli that causes edema disease, and enterotoxic Escherichia coli such as Escherichia coli can be cited as pathogens that are easily infected by livestock. Has antibacterial action.

サルモネラは各種動物の腸管に保菌され、その感染による家畜の生産性低下などの経済的損失が危惧されている。さらに、乳肉およびその製品や調理食品を媒体としてサルモネラ食中毒が併発している。近年、日本を含めた欧米諸国では鶏卵肉を起因とするSalmonella Enteritidis食中毒の発生が激増してきている。そこで、サルモネラの予防は生産段階で阻止することが最も大切であると考えられる。   Salmonella is carried in the intestinal tract of various animals, and there are concerns about economic losses such as reduced productivity of livestock due to infection. Furthermore, salmonella food poisoning has been accompanied by milk and its products and cooked foods. In recent years, the incidence of Salmonella Enteritidis food poisoning caused by chicken egg has increased dramatically in Western countries including Japan. Therefore, it is considered most important to prevent Salmonella at the production stage.

本発明に係る抗ウィルス又は抗菌剤は、牛、馬、豚、羊、ヤギなどの家畜用に、鶏、うずら、鴨、ダチョウなどの家禽用に、犬、猫などのペット用にそれらの病害の予防治療のため飼料に配合して用いることができ、魚介類としては、ハマチ、ブリ、鯛、鯉、鰻、エビ、アサリ、蛤等通常養殖されている魚介類の餌に適用することができる。   The antiviral or antibacterial agent according to the present invention is used for livestock such as cattle, horses, pigs, sheep and goats, for poultry such as chicken, quail, duck and ostrich, and for diseases such as pets such as dogs and cats. It can be used by mixing with feed for preventive treatment of fish, and as seafood, it can be applied to bait of seafood that is normally cultivated such as yellowtail, yellowtail, salmon, salmon, salmon, shrimp, clam, salmon, etc. it can.

本発明に係る抗ウィルス又は抗菌剤は、農作物に直接散布することもできるが、牛糞や豚糞の堆肥に混合し、該堆肥を農作物用の土壌に施すことにより、土壌中の病害菌を防除すること、ひいては、農作物を健全に生育することができる。農作物としては、カブの萎黄病・根こぶ病、キャベツの根こぶ病・バーティシリウム萎凋病、コマツナ、シロナの萎黄病、ダイコンの萎黄病・バーティシリウム黒点病、ハクサイの黄化病・根くびれ病・根こぶ病、ミズナの立枯病、ヒロシマナの根こぶ病、カボチャのフザリウム立枯病、キュウリのつる割病・苗立枯病・根立枯病、スイカのつる割病・苗立枯病、メロンの黒点根腐病・つる割病・苗立枯病・半身萎凋病・黒変根腐症、トマトの青枯病・萎凋病・褐色根腐病・苗立枯病、ナスの青枯病・半身萎凋病、イチゴの萎黄病・萎凋病・炭疽病、サヤエンドウの苗立枯病、シソの青枯病、シュンギクの萎凋病、ショウガの根茎腐敗病、タマネギの黒穂病・苗立枯病、ニンジンのしみ腐病、ニンニクの紅色根腐病、ネギの紅色根腐病・白絹病・苗立枯病・小菌核腐敗病、パセリの疫病、ホレンソウの萎凋病・株腐病・立枯病・根腐病、ミョウガの立枯症、ラッキョウの根腐病、ナシの白紋羽病、リンゴ、クワの白紋羽病・紫紋羽病、カーネーションの萎凋細菌病、シャクヤク、ボタンの根黒班病、ストックの萎凋病・立枯病、チューリップ、フリージア、ユリの球根腐敗病・首腐病・白絹病、バラの根頭がんしゅ病、リンドウ、センリョウの立枯病、タバコの疫病・角班病・黒根病・立枯病・野火病、サツマイモの紫紋羽病、コンニャクの白絹病・根腐病、サトイモの乾腐病、ジャガイモのそうか病・粉状そうか病、ヤマイモの褐色腐敗・根腐病、テンサイの叢根病・苗立枯病を挙げることができる。   The antiviral or antibacterial agent according to the present invention can be directly applied to agricultural crops, but it is mixed with cow manure or pig manure compost, and the compost is applied to the soil for agricultural crops to control pests in the soil. And, in turn, produce a healthy crop. Examples of crops include turnip yellowhead and root-knot, cabbage root-knot and verticillium wilt, komatsuna and shirona dwarf, radish yellow and verticillium sunspot, Chinese cabbage yellowing and root Constriction disease, root-knot disease, Mizuna root-knot disease, Hiroshima mana-knot disease, pumpkin fusarium blight disease, cucumber vine split disease, seedling blight disease, root-knot disease, watermelon vine crack disease, seedling blight Disease, black spot root rot, vine split rot, seedling blight, half body wilt, black root rot, tomato bacterial wilt, wilt, brown root rot, seed wilt, eggplant blue Blight, half body wilt, strawberry yellow, wilt, anthracnose, pea seedling blight, perilla wilt, syungia wilt, ginger rhizome rot, onion smut, seedling Disease, carrot blot rot, garlic red root rot, leek red root rot, white silk -Seedling blight, sclerotia nuclear rot, parsley plague, spinach wilt, stock rot, blight, root rot, myoga blight, rakkyo root rot, pear white crest feather Disease, apple, mulberry white scab, purple scab, carnation wilt bacterial disease, peonies, button root black spot disease, stock wilt, blight, tulip, freesia, lily bulb rot Neck rot, white silkworm, rose root cancer disease, gentian, senryo blight, tobacco epidemic, horn horn, black root, blight, wildfire, sweet potato purple crest, Examples include white silkworm and root rot of konjac, dry rot of taro, scab and powdery scab of potato, brown rot and root rot of yam, plexus root disease and seedling blight of sugar beet Can do.

本発明の培養基質原料として、常法の培養基質を用いることができるが、米ぬか、大豆粕、大豆胚芽、小麦フスマ、醤油粕、ポテトパルプ、こんにゃくトビ粉、卵殻、貝殻、天然鉱石等を１種又は２種以上用いることができる。前記培養基質原料を殺菌して用いることが雑菌等の混入を防ぐことができ好ましく、通常の殺菌方法、すなわち加圧水蒸気殺菌等の加熱殺菌を採用することができる。   As the culture substrate raw material of the present invention, a conventional culture substrate can be used. Rice bran, soybean meal, soybean germ, wheat bran, soy sauce cake, potato pulp, konjac powder, eggshell, shell, natural ore, etc. Two or more species can be used. It is preferable to sterilize and use the culture substrate raw material because it can prevent contamination of germs and the like, and a normal sterilization method, that is, heat sterilization such as pressurized steam sterilization can be employed.

本発明の各微生物の培養条件は、微生物の種類によって異なるが、乳酸菌類を含む場合は、温度２０〜４０℃、好ましくは、２５〜３２℃、ｐＨ４．０〜６．５、好ましくは、約ｐＨ５．０で、非通気下又は通気下で公知の方法により培養し、培地から菌体を分離し、菌体を洗浄し、湿菌体を得る。この場合、この湿菌体を公知の方法により凍結乾燥することもできる。得られた湿菌体又は凍結乾燥菌体を公知の方法により破砕し、該破砕物から細胞壁成分を分離する。   The culture conditions of each microorganism of the present invention vary depending on the type of microorganism, but when lactic acid bacteria are included, the temperature is 20 to 40 ° C., preferably 25 to 32 ° C., pH 4.0 to 6.5, preferably about At pH 5.0, the cells are cultured by a known method under non-aeration or aeration, and the cells are separated from the medium, and the cells are washed to obtain wet cells. In this case, the wet cells can be freeze-dried by a known method. The obtained wet cells or freeze-dried cells are crushed by a known method, and cell wall components are separated from the crushed material.

次に、得られた細胞壁成分を、例えば、冷５％トリクロロ酢酸溶液、冷０．５Ｍ水酸化ナトリウム溶液等の水系溶媒で抽出し、抽出画分を水に対して透析し、のち透析内液を凍結乾燥する。得られた水溶性画分を、公知のゲル濾過クロマトグラフィー（例えば、セファクリルＳ−４００等を使用）により精製し、得られる低分子画分を凍結乾燥し、多糖体を得ることができる。本発明の多糖類は、菌の細胞壁を構成する細胞壁成分として、該細胞壁及び／又は細胞壁破砕物から上記の方法により好適に単離されるが、該方法に限らず、それと同効のものであれば適宜の方法を使用することが可能である。   Next, the obtained cell wall component is extracted with an aqueous solvent such as a cold 5% trichloroacetic acid solution or a cold 0.5M sodium hydroxide solution, and the extracted fraction is dialyzed against water, and then the dialyzed internal solution. Freeze-dry. The obtained water-soluble fraction can be purified by known gel filtration chromatography (for example, using Sephacryl S-400 or the like), and the resulting low molecular fraction can be freeze-dried to obtain a polysaccharide. The polysaccharide of the present invention is suitably isolated from the cell wall and / or cell wall crushed material by the above method as a cell wall component constituting the cell wall of the fungus. Any appropriate method can be used.

細胞壁と培養液の両方に多糖類が存在する場合、培養物から目的とする多糖物質を採取するには、遠心分離、溶媒分画、ゲル濾過、イオン交換クロマトグラフィー、透析等の微生物が生産する水溶性多糖類の一般的な採取方法を単独あるいは適宜組み合わせて行えば良い。例えば、多糖物質生産菌の培養物から遠心分離によって、上澄区分と沈澱区分を得る。得られた液体区分にエチルアルコール、アセトン等の有機溶媒を加えることにより沈澱物が得られる。また、沈澱区分は、水、熱水等で抽出を行った後、遠心分離によって上澄を得、この上澄液にエチルアルコール、アセトン等の有機溶媒を加えて沈澱を得る。このようにして上澄区分と沈澱区分から得られた沈澱を水に再溶解し、不溶物を遠心分離、濾過等の方法によって除去した後、再度エチルアルコール、アセトン等の有機溶媒を加え沈澱を得る。得られた沈澱は、トリス−塩酸緩衝液等の適当な緩衝液に溶解し、同様の緩衝液で緩衝化されたジエチルアミノエチルセルロース等のイオン交換体を充填したカラムに負荷する。続いて同様の緩衝液を流し、非吸着区分を分取し、イオン交換水中で透析を行い、透析内液を凍結乾燥することにより、精製された多糖物質が得られる。   When polysaccharides are present in both the cell wall and the culture solution, microorganisms such as centrifugation, solvent fractionation, gel filtration, ion exchange chromatography, and dialysis are produced to collect the desired polysaccharide substance from the culture. A general method for collecting water-soluble polysaccharides may be used alone or in combination. For example, a supernatant section and a precipitate section are obtained from a culture of polysaccharide-producing bacteria by centrifugation. A precipitate is obtained by adding an organic solvent such as ethyl alcohol or acetone to the obtained liquid section. In the precipitation section, after extraction with water, hot water or the like, a supernatant is obtained by centrifugation, and an organic solvent such as ethyl alcohol or acetone is added to the supernatant to obtain a precipitate. In this way, the precipitate obtained from the supernatant section and the precipitation section is redissolved in water, insoluble matter is removed by centrifugation, filtration, etc., and then an organic solvent such as ethyl alcohol or acetone is added again to precipitate. obtain. The obtained precipitate is dissolved in a suitable buffer such as Tris-HCl buffer and loaded onto a column packed with an ion exchanger such as diethylaminoethylcellulose buffered with the same buffer. Subsequently, the same buffer solution is allowed to flow, the non-adsorption section is separated, dialyzed in ion-exchanged water, and the dialysis internal solution is freeze-dried to obtain a purified polysaccharide substance.

微生物を培養後、多糖類を存在させたまま用いる場合は、前述の処理を施すことなく生菌体を混入した培養液を用いることができる。   When microorganisms are cultured and used in the presence of polysaccharides, a culture solution mixed with viable cells can be used without performing the above-described treatment.

以下、実施例により本発明をより具体的に説明するが、本発明の技術的範囲はこれらの例示に限定されるものではない。   EXAMPLES Hereinafter, although an Example demonstrates this invention more concretely, the technical scope of this invention is not limited to these illustrations.

ラクトバチルス・アシドフィラス（L.acidophilus）をロゴサ培地で３７℃、２４時間培養した前培養液を、酵母エキス４％、ポリペプトン３％、乳糖１０％を含む液体培地に０．１（ｖ／ｖ）％接種し、ｐＨスタットを用いてｐＨ６．０〜６．５に苛性ソーダ水溶液で調整しながら３７℃、２２〜２４時間培養を行なった。培養終了後、連続遠心機で菌体を分離、回収した後、水を加えて元の液量まで希釈して再度連続遠心機で菌体を分離、回収した。この操作を合計４回繰り返して菌体を洗浄し、湿菌体を得た。この湿菌体を凍結乾燥した。得られた凍結乾燥菌体を破砕し、該破砕物から細胞壁成分を分離した。冷５％トリクロロ酢酸溶液、冷０．５Ｍ水酸化ナトリウム溶液の水系溶媒で抽出し、抽出画分を水に対して透析し、のち透析内液を凍結乾燥した。得られた水溶性画分を、セファクリルＳ−４００を用いてゲル濾過により精製し、得られた低分子画分を凍結乾燥し、多糖体を得た。同様に、バチルス・ナットウ（B.nattou）、ストレプトコッカス・フェカリス（S.faecalis）、サッカロミセス・セレビシアエ（S.cerevisiae）、キャンディダ・ユーティリス（C.utillis）及びピキア・ファリノサ（P.farinosa）を用いて各菌の適正な培地を用い、各菌の適正な培養条件を採用して、各菌の多糖体を得た。これらの多糖体を等量ずつを混合したものと硫酸カルシウム（三宝化学株式会社製）とを重量比１：１で混合し、混合物を得た。   Lactobacillus acidophilus (L. acidophilus) cultured in Rogosa medium at 37 ° C. for 24 hours is pre-cultured in a liquid medium containing 4% yeast extract, 3% polypeptone and 10% lactose (v / v). Inoculated at 37 ° C. for 22 to 24 hours while adjusting with a sodium hydroxide aqueous solution to pH 6.0 to 6.5 using a pH stat. After completion of the culture, the cells were separated and collected with a continuous centrifuge, then diluted with water to the original liquid volume, and again separated and collected with a continuous centrifuge. This operation was repeated a total of 4 times to wash the cells and obtain wet cells. The wet cells were lyophilized. The obtained freeze-dried cells were crushed, and cell wall components were separated from the crushed material. Extraction was performed with an aqueous solvent of a cold 5% trichloroacetic acid solution and a cold 0.5M sodium hydroxide solution, the extracted fraction was dialyzed against water, and then the dialyzed internal solution was freeze-dried. The obtained water-soluble fraction was purified by gel filtration using Sephacryl S-400, and the obtained low molecular fraction was freeze-dried to obtain a polysaccharide. Similarly, Bacillus nattou, Streptococcus faecalis, S. cerevisiae, C. utillis and P. farinosa. Using the appropriate medium of each bacterium, and employing the appropriate culture conditions for each bacterium, polysaccharides of each bacterium were obtained. An equal amount of these polysaccharides and calcium sulfate (manufactured by Sanpo Chemical Co., Ltd.) were mixed at a weight ratio of 1: 1 to obtain a mixture.

１０％脱脂粉乳培地１ｋｇにラクトバチルス・ヘルベティカスを接種し、３８℃にて３日間培養を行った。得られた培養液を遠心分離し(７,０００ｒｐｍ、２０分)上澄画分と沈澱画分を得た。得られた沈澱画分にイオン交換水３００ｍｌを加え、室温にて１時間攪拌して抽出を行い、その後、遠心分離(７,０００ｒｐｍ、１５分)を行った。得られた上澄画分を培養液からの上澄画分と合わせた後、エチルアルコールを最終濃度５０％になるように加えた。得られた沈澱物を遠心分離(１０,０００ｒｐｍ、１５分)によって回収後、イオン交換水に溶解し不溶性物質を遠心分離(１０,０００ｒｐｍ、１５分)によって除去した。この操作を３回繰り返した後、再度、エチルアルコールを最終濃度５０％になるように加え沈澱を得た。得られた沈澱を０.０２Ｍトリス−塩酸緩衝液(ｐＨ８.５)に溶解し、同緩衝液で緩衝化されたジエチルアミノエチルセルロースカラムに負荷し、同緩衝液を流し非吸着画分を分取した。得られた非吸着面画分を、流水中で１日透析した後、イオン交換水中で２日間透析を行った。得られた透析内液を凍結乾燥し、多糖類２００ｍｇを得た。同様に、バチルス・ズブチリス（B.subtilis）、ストレプトコッカス・ラクティス（S.lactis）、サッカロミセス・ロキシ（S.rouxii）、キャンディダ・アルビカンス（C.albicans）及びピキア・ファリノサ（P.farinosa）を用いて各菌の適正な培地を用い、各菌の適正な培養条件を採用して、各菌の多糖体を得た。これらの多糖体を等量ずつを混合したものと硫酸カルシウム（三宝化学株式会社製）とを重量比１：１で混合し、混合物を得た。   Lactobacillus helveticus was inoculated into 1 kg of 10% nonfat dry milk medium and cultured at 38 ° C. for 3 days. The obtained culture broth was centrifuged (7,000 rpm, 20 minutes) to obtain a supernatant fraction and a precipitate fraction. 300 ml of ion-exchanged water was added to the obtained precipitate fraction, and the mixture was extracted by stirring for 1 hour at room temperature, followed by centrifugation (7,000 rpm, 15 minutes). The obtained supernatant fraction was combined with the supernatant fraction from the culture solution, and then ethyl alcohol was added to a final concentration of 50%. The obtained precipitate was recovered by centrifugation (10,000 rpm, 15 minutes), dissolved in ion-exchanged water, and insoluble materials were removed by centrifugation (10,000 rpm, 15 minutes). After repeating this operation three times, ethyl alcohol was added again to a final concentration of 50% to obtain a precipitate. The resulting precipitate was dissolved in 0.02 M Tris-HCl buffer (pH 8.5), loaded onto a diethylaminoethyl cellulose column buffered with the same buffer, and the buffer was passed through to separate the non-adsorbed fraction. . The obtained non-adsorbed surface fraction was dialyzed in running water for 1 day, and then dialyzed in ion-exchanged water for 2 days. The obtained dialysis internal solution was freeze-dried to obtain 200 mg of polysaccharide. Similarly, using Bacillus subtilis (B. subtilis), Streptococcus lactis (S. lactis), Saccharomyces roxy (S. rouxii), Candida albicans and P. farinosa (P. farinosa) Then, using an appropriate medium for each bacterium, and employing an appropriate culture condition for each bacterium, polysaccharides for each bacterium were obtained. An equal amount of these polysaccharides and calcium sulfate (manufactured by Sanpo Chemical Co., Ltd.) were mixed at a weight ratio of 1: 1 to obtain a mixture.

米ぬか（水分１０％）１００重量部と貝殻（牡蠣粉末水分８％）１００重量部を混合し、この混合物を加圧水蒸気殺菌し、粉砕した。この混合物２００重量部に対し７０重量部の水を加えた。ここへ、バチルス・ナットウ（B.nattou）、ラクトバチルス・アシドフィラス（L.acidophilus）、ストレプトコッカス・フェカリス（S.faecalis）、サッカロミセス・セレビシアエ（S.cerevisiae）、キャンディダ・ユーティリス（C.utilis）及びピキア・ファリノサ（P.farinosa）（自社製の酵母を使用）の各々の菌を別に培養後、各菌数がほぼ１：１：１：１：１の割合となるように混合し、各４０重量部ずつ計２４０重量部を添加した。１ヶ月半、３５℃、ｐＨ６．０で静置発酵させた。その後、４ヶ月熟成し、その間１ヶ月に１度の割合で撹拌した。各菌の菌数は、バチルス・ナットウ（B.nattou）は１０５ＣＦＵ／１ｍｌ、ラクトバチルス・アシドフィラス（L.acidophilus）は１０５ＣＦＵ／１ｍｌ、ストレプトコッカス・フェカリス（S.faecalis）は１０５／１ｍｌ、サッカロミセス・セレビシアエ（S.cerevisiae）は１０５／１ｍｌ、キャンディダ・ユーティリス（C.utilis）は１０４ＣＦＵ／１ｍｌ、ピキア・ファリノサ（P.farinosa）は１０４ＣＦＵ／１ｍｌであった。前述の割合で大規模に培養させ、得られた培養物と硫酸カルシウム（三宝化学株式会社製）とを重量比１：１で配合した。該配合物を以下の実施例で「Ａ剤」と称して用いた。 100 parts by weight of rice bran (moisture 10%) and 100 parts by weight of shell (8% of oyster powder moisture) were mixed, and this mixture was sterilized by pressure steam and pulverized. 70 parts by weight of water was added to 200 parts by weight of this mixture. Here, Bacillus nattou, L. acidophilus, Streptococcus faecalis, S. cerevisiae, C. utilis And P. farinosa (using their own yeast) separately cultured, mixed so that the number of each bacterium is approximately 1: 1: 1: 1: 1, A total of 240 parts by weight was added by 40 parts by weight. It was allowed to stand and ferment at 35 ° C. and pH 6.0 for 1 and a half months. Thereafter, the mixture was aged for 4 months, and stirred at a rate of once per month. Bacterial count of each bacteria, Bacillus natto (B.nattou) is 10 5 CFU / 1 ml, Lactobacillus acidophilus (L. acidophilus) is 10 5 CFU / 1 ml, Streptococcus faecalis (S.faecalis) is 10 5 / 1 ml, Saccharomyces cerevisiae (S. cerevisiae) is 10 5/1 ml, Candida Yu Tirith (C.utilis) is 10 4 CFU / 1ml, Pichia Farinosa (P.farinosa) was 10 4 CFU / 1 ml . The large-scale culture was performed at the aforementioned ratio, and the obtained culture and calcium sulfate (manufactured by Sanpo Chemical Co., Ltd.) were blended at a weight ratio of 1: 1. The formulation was used in the following examples as “Agent A”.

実施例３において、各微生物を、バチルス・メガテリウム（B.megaterium）、ラクトバチルス・プランタラム（L.plantarum）、ストレプトコッカス・ラクティス（S.lactis）、サッカロミセス・セレビシアエ（S.cerevisiae）、キャンディダ・ユーティリス（C.utilis）及びピキア・ファリノサ（P.farinosa）（自社製の酵母を使用）を用いる以外は、実施例３と同様の方法で培養した。培養物中にはバチルス・メガテリウム（B.megaterium）は１０４ＣＦＵ／１ｍｌ、ラクトバチルス・プランタラム（L.plantarum）は１０５ＣＦＵ／１ｍｌ、ストレプトコッカス・ラクティス（S.lactis）は１０５ＣＦＵ／１ｍｌ、サッカロミセス・セレビシアエ（S.cerevisiae）は１０５ＣＦＵ／１ｍｌ、キャンディダ・ユーティリス（C.utilis）は１０５ＣＦＵ／１ｍｌ、ピキア・ファリノサ（P.farinosa）は１０４ＣＦＵ／１ｍｌであった。前述の割合で大規模に培養させて得られた培養物と硫酸カルシウム（塩田から排出された純度２５％以上の石膏）とを重量比１：１で配合し、混合物を得た。 In Example 3, each microorganism was transformed into Bacillus megaterium, L. plantarum, Streptococcus lactis, S. cerevisiae, C. cerevisiae, Candida The cells were cultured in the same manner as in Example 3 except that C.utilis and P.farinosa (using their own yeast) were used. During culture Bacillus megaterium (B.megaterium) is 10 4 CFU / 1ml, Lactobacillus plantarum (L. plantarum) is 10 5 CFU / 1ml, Streptococcus lactis (S.lactis) is 10 5 CFU / 1 ml, S. cerevisiae was 10 5 CFU / 1 ml, C. utilis was 10 5 CFU / 1 ml, and P. farinosa was 10 4 CFU / 1 ml. It was. A culture obtained by culturing on a large scale at the above-mentioned ratio and calcium sulfate (gypsum with a purity of 25% or more discharged from the salt pad) were blended at a weight ratio of 1: 1 to obtain a mixture.

［Ａ剤対動物病原菌の抗菌実験］
（方法）
ブロイラー雛は孵卵場から輸送後、試験区では搬入時に実施例３により製造されたＡ剤をヒナに直接振りかけてからＡ剤を散布してある堆積飼料敷料に雛を放し、０．３％Ａ剤混合の飼料を給与して１８日令まで飼育した。対照区は新鮮なチップを敷料とする通常の方法で飼育した。両区とも３日令の雛にS.Enteritidis１０３、１０５，１０７ ＣＦＵ／ｍｌをそれぞれ２５羽づつに経口投与した（ＣＦＵは、ｃｏｌｏｎｙ ｆｏｒｍｉｎｇ ｕｎｉｔの略）。（１）両区の雛は１１日令にそれぞれ１５羽を、１８日令にそれぞれ１０羽を屠殺して盲腸便を採取した。その盲腸便は１０倍段階希釈を行い、その適切な希釈液をＤＨＬ培地（極東製薬株社製）とＳＳ培地（極東製薬株社製）に塗抹して３７℃で培養した。（２）適切な希釈液と１１日令の屠体から取り出した肝臓を、ＤＨＬ培地とＡ剤培地に塗抹した。その残渣はセレナイト培地に投入して、それぞれ４２℃で１〜２日間の増菌培養を行った後、ＤＨＬ培地とＡ剤培地に画線した。培地上に発現した疑わしい集落は性状試験を実施した。また、１１日令と１８日令の盲腸便ではｐＨと有機酸の定量分析も行った。本試験は再現性を確認するため２回行った。 [Antimicrobial experiment of agent A versus animal pathogens]
(Method)
Broiler chicks are transported from the hatchery, and in the test area, the chicks are released on the piled litter on which the agent A is sprayed after directly spraying the agent A produced in Example 3 at the time of delivery. The mixed feed was fed and reared until the 18th day. The control group was reared by the usual method using fresh chips as a bedding. In both wards, S. Enteritidis 10 3 , 10 5 , and 10 7 CFU / ml were orally administered to 25-day-old chicks (CFU is an abbreviation of colony forming unit). (1) The chicks in both wards were slaughtered on the 11th day and 15 chicks on the 18th day, and the cecal feces were collected. The caecal stool was diluted 10-fold, and the appropriate dilution was smeared on DHL medium (Kyokuto Pharmaceutical Co., Ltd.) and SS medium (Kyokuto Pharmaceutical Co., Ltd.) and cultured at 37 ° C. (2) Appropriate dilutions and livers removed from 11-day-old carcasses were smeared on DHL medium and A-agent medium. The residue was put into a selenite medium and subjected to enrichment culture for 1 to 2 days at 42 ° C., respectively, and then streaked into a DHL medium and an A agent medium. Suspicious settlements developed on the medium were subjected to a property test. In addition, 11-day and 18-day cecal stools were also subjected to quantitative analysis of pH and organic acid. This test was performed twice to confirm reproducibility.

（結果）
(１)盲腸中のサルモネラについて
（ａ）Ａ剤給与の試験区においては、S.Enteritidis１０３ＣＦＵ／ｍｌ感染雛の盲腸便からサルモネラは、１１日令と１８日令の両方で検出されなかった。またS.Enteritidis１０５ＣＦＵ／ｍｌ感染雛の盲腸便からサルモネラは１１日令の１５個体と１８日令の１０個体のうち、それぞれ３例と２例で１０３〜１０５／ｇの範囲で検出され、増菌培地からは１１日令の１５個体のうちから１例から分離された。しかし、平均菌数では試験区は対照区の１０分の１であった。さらにS.Enteritidis１０７ＣＦＵ／ｍｌ感染雛の盲腸では１１日令と１８日令に、それぞれ１５個体のうち６例と１０個体のうち３例から１０２〜１０７／ｇの範囲で検出され、またそれぞれ１例づつが増菌培地から分離された。（ｂ）一方、Ａ剤給与を行わなかった対照区では、１１日令と１８日令ともに全ての接種濃度で１００％サルモネラが検出された。具体的に表１に示す。 (result)
(1) Salmonella in the cecum (a) Salmonella was not detected from the cecal feces of S. Enteritidis 10 3 CFU / ml infected chicks in both the 11th and 18th ages in the A-group-fed test plot . Salmonella was detected in the range of 10 3 to 10 5 / g in 3 cases and 2 cases out of 15 individuals at 11 days and 10 individuals at 18 days from the cecal feces of S. Enteritidis 10 5 CFU / ml infected chicks. From the enrichment medium, it was isolated from 1 case out of 15 individuals aged 11 days. However, in the average number of bacteria, the test group was 1/10 of the control group. Furthermore, in the cecum of S. Enteritidis 10 7 CFU / ml infected chicks, it was detected in the range of 10 2 to 10 7 / g from 6 of 15 individuals and 3 of 10 individuals at 11 and 18 days of age, respectively. Each one was isolated from the enrichment medium. (B) On the other hand, 100% Salmonella was detected at all inoculation concentrations in the control group in which the agent A was not fed. Specifically, it is shown in Table 1.

（結果）
（２）肝臓中のサルモネラについて
肝臓中のサルモネラ検査は１１日令の１０屠体について行った。S.Enteritidis１０３ＣＦＵ／ｍｌ感染雛の場合、試験区ではサルモネラは検出されず、対照区では半数がサルモネラに侵されていた。またS.Enteritidis１０５ＣＦＵ／ｍｌ感染雛では試験区１０％と対照区６０％で、S.Enteritidis１０７ＣＦＵ／ｍｌ感染雛でも、それぞれ５０％と８０％で検出され、各接種濃度においてサルモネラの検出割合は対照区が試験区を上回っていた。具体的に表２に示す。 (result)
(2) About Salmonella in the liver The Salmonella test in the liver was conducted on 10 carcasses of 11 days old. In the case of S. Enteritidis 10 3 CFU / ml infected chicks, no Salmonella was detected in the test group, and half was affected by Salmonella in the control group. In addition, S. Enteritidis 10 5 CFU / ml infected chicks were detected in 10% test group and 60% control group, and S. Enteritidis 10 7 CFU / ml chicks were detected in 50% and 80%, respectively. The ratio was higher in the control plot than in the test plot. Specifically, it is shown in Table 2.

[Ａ剤堆肥のキュウリつる割病菌（Fusarium oxy.f.sp.cucumerinum）の静菌作用試験]
（試料の調整）
試料はミキサーで粉砕後、４０〜５０％の水分になるよう加え、２４時間室温で放置した。試料の減菌処理は、試料をガラスシャーレ（９ｃｍ）に１５ｇ入れ、蓋をした状態で１２１℃、１５分間オートクレーブを用いて行った。
（静菌作用の確認）
（１）病原菌の培養
予めＰＤＡ寒天培地（ポテト・デキストロース寒天培地）に平板培養したキュウリつる割病原菌を寒天ごと１ｃｍ角に切り取り、ＰＤ液体培地（ポテト・デキストロース液体培地）に接種し。３０℃、１２０ｒｐｍ、５日間振とう培養した。
（２）静菌作用の確認
（i）病原菌胞子の洗浄
液体培養したキュウリつる割病菌を３層ガーゼでろ過し、ろ液を遠心分離（３，６００ｒｐｍ、１０分間）して上澄み液を除去する。次に沈殿物に減菌水を加え懸濁し、再度、遠心分離し、上澄み液を除去する。この操作を３度繰り返し、胞子を洗浄する。
（ii）病原菌胞子のスライドガラスへの固定
洗浄した胞子に減菌水を加え、懸濁し、懸濁液を減菌処理した１％素寒天溶液（４３℃前後に冷ましたもの）と混合する。
（iii) 静菌作用の確認
試料を１５ｇ入れたガラスシャーレ（９ｃｍ）に、胞子を固定したスライドガラスを、固定した面が堆肥に接するように押し付け、ふたをして２８℃、２０時間培養する。培養後スライドガラスを取り出し、水で洗浄して乾燥する。乾燥後、フェノールローズベンガル染色液で胞子を染色し、顕微鏡で胞子の発芽率を測定する。尚、各試料とも減菌処理なし、および減菌処理あり、ともに反復を２とした。 [Bacteriostatic action test of Fusarium oxy.f.sp.cucumerinum]
(Sample adjustment)
The sample was pulverized with a mixer, added to 40 to 50% moisture, and left at room temperature for 24 hours. The sample was sterilized by placing 15 g of the sample in a glass petri dish (9 cm) and covering the sample with an autoclave at 121 ° C. for 15 minutes.
(Confirmation of bacteriostatic action)
(1) Cultivation of pathogenic bacteria Cucumber vine split pathogens previously plated on PDA agar medium (potato dextrose agar medium) were cut into 1 cm squares together with agar and inoculated into PD liquid medium (potato dextrose liquid medium). The culture was shaken at 30 ° C., 120 rpm for 5 days.
(2) Confirmation of bacteriostatic action (i) Washing of pathogenic fungus spores Liquid-cultured cucumber vine split fungi are filtered with a three-layer gauze, and the filtrate is centrifuged (3,600 rpm, 10 minutes) to remove the supernatant. . Next, sterilized water is added to the precipitate to suspend it, and centrifuged again to remove the supernatant. This operation is repeated three times to wash the spores.
(Ii) Fixation of pathogenic spore on slide glass Add sterilized water to the washed spore, suspend, and mix the suspension with sterilized 1% undiluted agar solution (cooled to around 43 ° C).
(Iii) Confirmation of bacteriostatic action A glass slide (9 cm) containing 15 g of a sample is pressed with a glass slide with spores fixed so that the fixed surface is in contact with the compost, covered, and cultured at 28 ° C. for 20 hours. . After incubation, the slide glass is taken out, washed with water and dried. After drying, the spores are stained with a phenol rose bengal stain and the germination rate of the spores is measured with a microscope. Each sample had no sterilization treatment and sterilization treatment, and the number of repetitions was 2.

（Ａ剤対土壌病原菌の拮抗実験）
健全な土壌にフザリウム菌を予め接種しておき、本発明のＡ剤添加各堆肥は、各堆肥のＡ剤５０重量％となるように混合し、土壌に通常の堆肥の半分の量を土壌に散布した。比較例として、堆肥なし土壌を用いた。比較例の堆肥なし土壌区、本発明のＡ剤添加牛糞堆肥土壌区、本発明のＡ剤添加豚糞土壌区、比較例の一般豚糞堆肥土壌区において、キュウリの苗を５月の初旬に植え、６〜７月のキュウリ生育量、つる割病の発生状況を調べた。その結果を表３に示す。 (Competition experiment of agent A versus soil pathogen)
Fusarium bacteria are inoculated in a healthy soil in advance, and each compost added with the agent A of the present invention is mixed so that it becomes 50% by weight of the compost A, and half the amount of normal compost is added to the soil. Scattered. As a comparative example, soil without compost was used. At the beginning of May in the compost-free soil section of the comparative example, the A-added cow manure compost soil section of the present invention, the A-added pig manure soil section of the present invention, and the general swine manure compost soil section of the comparative example Planting, cucumber growth from June to July, and the occurrence of vine split disease were examined. The results are shown in Table 3.

表３に示すように、フザリウム菌の接種によって、比較例の堆肥なし土壌区及び一般豚糞堆肥土壌区共に高い比率でキュウリつる割病が発生したのに対し、本発明のＡ剤牛糞堆肥土壌区及びＡ剤豚糞堆肥土壌区は、共に顕著な抑制効果を示した。それによって、キュウリ生育量も増加していることがわかった。   As shown in Table 3, the inoculation with Fusarium fungus caused cucumber vine split disease at a high rate in both the non-compostable soil area and the general swine dung compost soil area of the comparative example, whereas the A agent cattle dung compost soil of the present invention Both the ward and the A agent swine manure compost soil group showed a remarkable inhibitory effect. As a result, it was found that cucumber growth also increased.

［フザリウム菌に対する静菌作用(胞子伸長抑制) ］
（１）試験方法
フザリウム菌を培養したシャーレに一定量のＡ剤堆肥を添加して（Ａ剤添加豚糞、Ａ剤添加鶏糞）一定時間経過後の菌の胞子の伸長抑制効果（静菌作用）を、対照区とあわせて調査し、フザリウム菌の胞子伸張の様子を撮ったものを図１（写真、Ａ剤添加豚糞）、図２（写真、Ａ剤添加鶏糞）、図３（写真、豚糞の対照区）に示す。
図１〜３で明らかなように、Ａ剤添加堆肥は、いずれもフザリウム菌胞子の伸張を抑制する効果（静菌作用）を有することが判明した。この結果は、実施例の植物を用いた栽培試験の結果を裏付けるものといえる。 [Bacteriostatic action against Fusarium bacteria (suppression of spore elongation)]
(1) Test method
Add a certain amount of agent A compost to the petri dish with Fusarium cultivated (agent A-added swine feces, agent A-added chicken manure) to prevent the growth of fungal spores (bacteriostatic action) after a certain period of time. Figure 1 (photograph, A-pigmented pig feces), Figure 2 (photograph, A-pigmented chicken feces), Figure 3 (photograph, pig feces control) Ward).
As is apparent from FIGS. 1 to 3, it was found that the A-agent-added compost has an effect (bacteriostatic action) for suppressing the extension of Fusarium spore. It can be said that this result supports the result of the cultivation test using the plant of the Example.

［ネコブ病に対するＡ剤牛糞堆肥の効果］
お互いに隣接する農家のブロッコリー栽培圃場で、Ａ剤添加牛糞堆肥施用の圃場でネコブ病が大幅に抑制され（図４参照）、隣接土壌では大発生したので（図５参照）、これらの土壌、ネコブ病菌を接種した健全土壌、常時ネコブ病発生の汚染土壌を用いて発病株率、発病度を調べた。その結果を表４に示す。 [Effects of cattle manure compost A for feline disease]
In the field of broccoli cultivation of the farmhouses adjacent to each other, the root-knot disease was greatly suppressed in the field where the A-agent-added cow manure compost was applied (see FIG. 4), and a large outbreak occurred in the adjacent soil (see FIG. 5). The disease strain rate and disease severity were examined using healthy soil inoculated with root-knot fungus and contaminated soil with normal root-knot disease. The results are shown in Table 4.

表４に示すように、Ａ剤添加牛糞堆肥を施用した土壌は、ネコブ病の発生を完全に抑制したのに対し、他の区はいずれもネコブ病が全面的に発生し、現地における栽培状況を裏付ける結果となった。   As shown in Table 4, the soil applied with A-added cattle manure compost completely suppressed the occurrence of root-knot disease, while all other areas were completely affected by root-knot disease, and the local cultivation situation As a result,

［Ａ剤対エビウィルス病拮抗試験］
ベトナム公平郡の養殖池で、ブラックタイガーを養殖中２００４年７月１５日にホワイトスポット複合ウィルス感染症を発症、その病症は、頭部が赤く、腫れがあり、胸部には白点があった（図６、写真参照）。２００４年７月１６日にＡ剤を２〜３ｋｇ／ａ／回投入したところ、３日後には、エビは元気に回復し、前述の病症は消えた（図７，８、写真参照）。これより、Ａ剤に抗ウィルス効果が認められた。また、２００４年８月１５日においてもウィルス発症の再発はなく（図９〜１１、写真参照）、Ａ剤の抗ウィルス持続効果が認められた。 [A drug versus shrimp virus disease antagonism test]
A black tiger was cultivated in an aquaculture pond in Viet Nam, Vietnam. A white spot compound virus infection developed on July 15, 2004. The disease was red in the head, swollen, and white on the chest. (See FIG. 6, photo). When 2-3 kg / a / injection of agent A was introduced on July 16, 2004, shrimp recovered well after 3 days, and the above-mentioned disease disappeared (see FIGS. 7 and 8 and photographs). From this, the antiviral effect was recognized by the A agent. Further, on August 15, 2004, there was no recurrence of virus onset (see FIGS. 9 to 11 and photographs), and the antiviral sustained effect of agent A was observed.

本発明のＡ剤添加豚糞におけるフザリウム菌の胞子伸張抑制の様子を示す写真である。It is a photograph which shows the mode of the spore expansion | extension suppression of a Fusarium bacterium in swine stool addition of A agent of this invention. 本発明のＡ剤添加鶏糞におけるフザリウム菌の胞子伸張抑制の様子を示す写真である。It is a photograph which shows the mode of the spore expansion | extension suppression of a Fusarium microbe in the A-drug addition chicken feces of this invention. 対照区（豚糞）のフザリウム菌の胞子伸張の様子を示す写真である。It is a photograph which shows the mode of the spore expansion | swelling of a Fusarium microbe in a control plot (pig feces). 本発明のＡ剤添加牛糞堆肥施用の圃場でネコブ病が抑制された様子を示す写真である。It is a photograph which shows a mode that the root-knot disease was suppressed in the field of A agent addition cow manure compost application of this invention. 対照区のＡ剤を施用しない本発明圃場の隣接圃場におけるネコブ病多発を示す写真である。It is a photograph which shows frequent occurrence of the root-knot disease in a field adjacent to the field of the present invention where the agent A of the control group is not applied. Ａ剤を養殖池無投入のホワイトスポット複合ウィルス感染症に罹ったブラックタイガーを撮った写真である。It is the photograph which took the black tiger who suffered from the white spot compound virus infection without culture pond input of A agent. 本発明のＡ剤を養殖池に投入３日後の手のひらにのせて撮ったブラックタイガーの写真である。It is the photograph of the black tiger taken on the palm 3 days after throwing the A agent of this invention into a culture pond. 図７の方向を変えて撮ったブラックタイガーの写真である。It is the photograph of the black tiger taken by changing the direction of FIG. 本発明のＡ剤投入１月後のブラックタイガーを撮った写真である。It is the photograph which took the black tiger one month after A agent introduction of this invention. 図９と同日の本発明の多数のブラックタイガーを撮った写真である。10 is a photograph of a number of black tigers of the present invention on the same day as FIG. 9. 図９と同日の本発明の養殖池におけるブラックタイガーを撮った写真である。It is the photograph which took the black tiger in the culture pond of this invention on the same day as FIG.

Claims (19)

バチルス（Bacillus）属、ラクトバチルス（Lactobacillus）属、ストレプトコッカス（Strptococcus）属、サッカロミセス（Saccharomyces）属、キャンディダ（Candida）属及びピキア（Pichia）属に属する微生物を含む微生物由来の多糖類と硫酸カルシウムとを有効成分として含有することを特徴とする抗ウイルス又は抗菌剤。 Polysaccharides and calcium sulfate derived from microorganisms including microorganisms belonging to the genera Bacillus, Lactobacillus, Strptococcus, Saccharomyces, Candida and Pichia As an active ingredient. 微生物として、さらに、耐塩性酵母菌、耐塩性乳酸菌、硝化細菌、硫黄細菌、メタン酸化細菌、硫黄還元細菌、光合成細菌、好塩菌の群から選ばれる１種又は２種以上を用いることを特徴とする請求項１記載の抗ウイルス又は抗菌剤。 Further, as the microorganism, one or more kinds selected from the group of salt-resistant yeast, salt-resistant lactic acid bacteria, nitrifying bacteria, sulfur bacteria, methane oxidizing bacteria, sulfur-reducing bacteria, photosynthetic bacteria, and halophilic bacteria are used. The antiviral or antibacterial agent according to claim 1. 微生物由来の多糖類が、その生菌体及び／又は死菌体を含むことを特徴とする請求項１又は２記載の抗ウイルス又は抗菌剤。 3. The antiviral or antibacterial agent according to claim 1 or 2, wherein the microorganism-derived polysaccharide contains its living cells and / or dead cells. さらに、藻類を含有することを特徴とする請求項１〜３のいずれか記載のウイルス又は抗菌剤。 Furthermore, algae are contained, The virus or antibacterial agent in any one of Claims 1-3 characterized by the above-mentioned. バチルス（Bacillus）属に属する微生物が、バチルス・ズブチルス（Bacillus subtilis）、バチルス・ナットウ（Bacillus natto）、バチルス・メガテリウム（Bacillus megaterium）の群から選ばれる１種又は２種以上であることを特徴とする請求項１〜４のいずれか記載の抗ウイルス又は抗菌剤。 The microorganism belonging to the genus Bacillus is one or more selected from the group of Bacillus subtilis, Bacillus natto, and Bacillus megaterium. The antiviral or antibacterial agent according to any one of claims 1 to 4. ラクトバチルス（Lactobacillus）属に属する微生物が、ラクトバチルス・アシドフィラス（Lactobacillus acidophilus）、ラクトバチルス・プランタラム（Lactobacillus plantarum）、ラクトバチルス・ブレビス（Lactobacillus brevis）、ラクトバチルス・カゼイ（Lactobacillus casei）の群から選ばれる１種又は２種以上であることを特徴とする請求項１〜４のいずれか記載の抗ウイルス又は抗菌剤。 The microorganism belonging to the genus Lactobacillus is from the group of Lactobacillus acidophilus, Lactobacillus plantarum, Lactobacillus brevis, Lactobacillus casei (Lactobacillus casei) The antiviral or antibacterial agent according to any one of claims 1 to 4, wherein the antiviral or antibacterial agent is one or more selected. ストレプトコッカス（Streptococcus）属に属する微生物が、ストレプトコッカス・フェカリス（Streptococcus faecalis）、ストレプトコッカス・ラクティス（Streptococcus lactis）、ストレプトコッカス・サーモフィルス（Streptococcus thermophillus）の群から選ばれる１種又は２種以上であることを特徴とする請求項１〜４のいずれか記載の抗ウイルス又は抗菌剤。 The microorganism belonging to the genus Streptococcus is one or more selected from the group of Streptococcus faecalis, Streptococcus lactis, Streptococcus thermophillus The antiviral or antibacterial agent according to any one of claims 1 to 4. サッカロミセス（Saccharomyces）属に属する微生物が、サッカロミセス・セレビシアエ（Saccharomyces cerevisiae）であることを特徴とする請求項１〜４のいずれか記載の抗ウイルス又は抗菌剤。 The antiviral or antibacterial agent according to any one of claims 1 to 4, wherein the microorganism belonging to the genus Saccharomyces is Saccharomyces cerevisiae. キャンディダ（Candida）属に属する酵母が、キャンディダ・ユーティリス（Candida utilis）であることを特徴とする請求項１〜４のいずれか記載の抗ウイルス又は抗菌剤。 The antiviral or antibacterial agent according to any one of claims 1 to 4, wherein the yeast belonging to the genus Candida is Candida utilis. ピキア属に属する酵母が、ピキア・メンブラナエファシエンス（Pichia membranaefacience）であることを特徴とする請求項１〜４のいずれか記載の抗ウイルス又は抗菌剤。 The antiviral or antibacterial agent according to any one of claims 1 to 4, wherein the yeast belonging to the genus Pichia is Pichia membranaefacience. 請求項１〜１０記載のいずれかを含むことを特徴とする家禽・家畜用感染防除剤。 The infection control agent for poultry and livestock characterized by including either of Claims 1-10. 請求項１〜１０記載のいずれかを含むことを特徴とするペット用感染防除剤。 A pet infection control agent comprising any one of claims 1 to 10. 請求項１〜１０記載のいずれかを含むことを特徴とする飼料。 A feed comprising any one of claims 1 to 10. 請求項１〜１０記載のいずれかを含むことを特徴とする土壌病害防除剤。 A soil disease control agent comprising any one of claims 1 to 10. 請求項１〜１０記載のいずれかを含むことを特徴とする肥料。 A fertilizer comprising any one of claims 1 to 10. 請求項１〜１０記載のいずれかを含むことを特徴とする植物病害防除剤又は植物生長調整剤。 A plant disease control agent or plant growth regulator comprising any one of claims 1 to 10. 請求項１〜１０記載のいずれかを含むことを特徴とする魚介類の感染防除剤。 An infection control agent for fish and shellfish comprising any one of claims 1 to 10. 請求項１〜１０記載のいずれかを含むことを特徴とする水産養殖用餌。 An aquaculture bait comprising any one of claims 1 to 10. 請求項１〜１０記載のいずれかを含むことを特徴とするヒト用感染防除剤。 A human infection control agent comprising any one of claims 1 to 10.
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