WO2005089780A1 - Composition against aids virus and method of selectively inactivating virus-infected cells - Google Patents

Composition against aids virus and method of selectively inactivating virus-infected cells Download PDF

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Publication number
WO2005089780A1
WO2005089780A1 PCT/JP2005/004977 JP2005004977W WO2005089780A1 WO 2005089780 A1 WO2005089780 A1 WO 2005089780A1 JP 2005004977 W JP2005004977 W JP 2005004977W WO 2005089780 A1 WO2005089780 A1 WO 2005089780A1
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Prior art keywords
virus
cells
antiviral
infected
infected cells
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PCT/JP2005/004977
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French (fr)
Japanese (ja)
Inventor
Keiji Umeda
Taro Shirakawa
Katsunobu Sakai
Yositaka Nadachi
Takehiko Fujino
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Umeda Jimusho Ltd.
Institute Of Rheological Function Of Food Co., Ltd.
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Priority to JP2006511247A priority Critical patent/JPWO2005089780A1/en
Publication of WO2005089780A1 publication Critical patent/WO2005089780A1/en

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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00Medicinal preparations containing inorganic active ingredients
    • A61K33/18Iodine; Compounds thereof
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23LFOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/16Inorganic salts, minerals or trace elements
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/045Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • A61K31/05Phenols
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/16Amides, e.g. hydroxamic acids
    • A61K31/18Sulfonamides
    • 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
    • A61P31/18Antivirals for RNA viruses for HIV
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23VINDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00Food compositions, function of food ingredients or processes for food or foodstuffs

Definitions

  • the present invention relates to an anti-AIDS virus composition and a method for selectively inactivating virus-infected cells.
  • the present invention relates to an antiviral composition exhibiting an excellent antiviral action against an AIDS virus or the like, and more particularly, to a virus-infected cell infected with a virus such as an AIDS virus.
  • the present invention relates to an antiviral composition having an inactivating function, a functional food to which the antiviral property is added, and an antiviral drug.
  • INDUSTRIAL APPLICABILITY The present invention has an effect of selectively inactivating and killing virus-infected cells in a living cell system in a technical field such as an antiviral preparation applied to a viral disease caused by infection of various viruses such as an AIDS virus.
  • the present invention provides an antiviral composition and a use thereof. For example, the present invention selectively inactivates AIDS virus-infected cells, viral cancer cells, etc., and prevents, treats, and functional foods for these diseases. It is intended to provide useful new drugs and functional foods.
  • Patent Document 1 Japanese Patent Laid-Open No. 5-294838
  • Patent Document 2 Japanese Patent Application Laid-Open No. 2002-293803
  • the present inventors have considered in view of the above-mentioned prior art that prevention and treatment of viral infectious diseases caused by various viruses such as the AIDS virus, which is low in cost and highly safe, can be performed.
  • the new eodo supply system developed by the present inventors for virus-infected cells using eodo ions.
  • the present inventors have found that the intended purpose can be achieved, and have conducted further studies to complete the present invention.
  • the present invention provides a specific antiviral effect of selectively inactivating virus-infected cells by utilizing an eodo-supply system using oodoion in virus-infected cells such as AIDS virus-infected cells. It is an object of the present invention to provide a novel antiviral composition, a functional food containing the antiviral composition, an antiviral drug, and the like.
  • the present invention for solving the above-mentioned problems includes the following technical means.
  • An antiviral composition having an action to selectively inactivate virus-infected cells, characterized by containing as an active ingredient an ore ion or a compound that produces an ore ion.
  • a functional food having an antiviral function wherein the antiviral composition according to the above (1) or (2) is blended to add an antiviral function.
  • An antiviral drug having an action of selectively inactivating virus-infected cells comprising the antiviral composition according to (1) or (2).
  • the virus (1Z2I) acts to selectively inactivate and kill virus-infected cells.
  • a method for selectively inactivating virus-infected cells comprising:
  • the antiviral composition of the present invention is characterized in that it contains, as an active ingredient, an ode ion or a compound that generates an ode ion. Ode (1Z2I) production to supply specifically to cell lines to produce eodo (1Z2I) in virus-infected cells-
  • the present invention provides the following novel findings discovered by the present inventors; (1) generation of eaves on the anode side due to electrolysis of ionic ion water; ⁇ ⁇ [ ⁇ ⁇ ] ⁇ 1 ⁇ 2 ⁇ , (2) live cells
  • the distribution center of normal cells is neutral ⁇ 0, and the distribution center of virus-infected cells is on the minus side.
  • infectious hematopoietic necrosis virus that infects salmon
  • the mode ion has been found to be deelectronized to produce eodes because it has an environment similar to (1) above, and (4) the inodes in infected cells inactivate viruses or cells. It was created based on the fact that it was recognized.
  • FIG. 1 shows an example of an apparatus used for carrier-free electrophoresis of living cells of a living tissue.
  • a is the anode (platinum)
  • b is the connection of the anode terminal
  • c is the force sword (platinum)
  • e is the filter paper
  • f is the filter paper that prevents cell diffusion
  • g is the buffer
  • h is the buffer.
  • a magnetic ferrite rubber part for mounting means for dividing into two parts, i is a plastic plate used for separating the apparatus into electrophoresis.
  • the device was controlled at 15 ° C for fish cells or 37 ° C for animal cells. The arrow indicates the position of the cross section.
  • FIG. 2 shows an electrophoretic diagram of virus-infected RTG-2 cells (cultivable cells collected from germ-line glands of -mouth trout and cultured host cells of the IHN virus or the like). These are electropherograms of virus-infected RTG-2 cells.
  • electrophoresis was performed at 15 ° C in MEM one day after infection with the IHN virus. Electrophoresis was performed 3 days later.
  • C g-strophantin or sodium azide was added 5 days after the infection and electrophoresis was performed in MEM.
  • D electrophoresis was performed 5 days after the infection.
  • E the cells were electrophoresed at 15 ° C in MEM.
  • FIG. 3 shows electropherograms of live RTG-2 cells and CHSE-214 cells (culturable cells collected from trout (masunosuke) and host culture cells of IHN virus or the like). These cells show that 107 Zlml of RTG-2 cells or CHSE-214 cells were calored in the center of the electrophoresis apparatus.
  • electrophoresis (20 mA, 15 minutes in DC) was performed with EBSS at pH pH 7.0. The results of electrophoresis at 0 are shown.
  • examples of ⁇ and Nal are given as examples of ⁇ or Nal as a compound that produces ⁇ or ion, but any compound that produces ⁇ ⁇ can be used as long as it is not limited to these. .
  • the antiviral activity can be further enhanced by combining a polyphenol compound such as humic acid, tea power techin, or the like with the anode.
  • a polyphenol compound such as humic acid, tea power techin, or the like
  • an antiviral composition can be prepared by combining these compounds with, for example, a pharmaceutically acceptable carrier.
  • a functional food having an antiviral function can be obtained.
  • the antiviral composition can be used as an antiviral drug.
  • sodium eodo-sodium Z polyphenols such as tea catechin or humic acid
  • a net charge in carrier-free electrophoresis of a cell is set as a marker, and a neutral charge is set at a normal point, and a positive / negative charge shift of a neutral point force is calculated.
  • a measure of the metabolic abnormalities of cells it is possible to fractionate sample cells alive using an electrophoresis apparatus and measure their distribution.
  • an active ingredient that controls cell abnormalities can be specified. Also
  • Ode ions or olude ions to be incorporated into the antiviral composition of the present invention The amount of the compound to be produced is as long as the desired effect of the present invention is exhibited.
  • the antiviral composition of the present invention may contain diluents or excipients such as fillers, bulking agents, binders, humectants, disintegrants, surfactants, and lubricants which are usually used in pharmaceutical preparations. It is prepared using The form of this composition can be selected according to the purpose of treatment, and typical examples include tablets, pills, powders, solutions, suspensions, emulsions, granules, capsules, and injections (solutions). , Suspending agents, etc.).
  • composition of the present invention may contain conventional additives such as vitamins, hormonal agents, pharmacologic agents such as amino acids, surfactants, pigments, dyes, pigments, fragrances, ultraviolet absorbers, humectants, and humectants.
  • vitamins, hormonal agents, pharmacologic agents such as amino acids, surfactants, pigments, dyes, pigments, fragrances, ultraviolet absorbers, humectants, and humectants.
  • a tackifier, an antioxidant, a sequestering agent, a pH adjuster, and the like can be arbitrarily added as necessary.
  • examples of the carrier include excipients such as glucose, lactose, starch, cocoa butter, hydrogenated vegetable oil, kaolin, and talc; binders such as gum arabic, tragacanth, gelatin, and ethanol; laminaran; And disintegrating agents such as agar.
  • the solvents, emulsions and suspensions are preferably sterile and isotonic with blood.
  • water, ethyl alcohol, propylene glycol, polyoxyethylene sorbitan fatty acid ester and the like can be used as the diluent.
  • the compounding method and administration method of the antiviral composition or the drug thereof of the present invention are not particularly limited, and are compounded by a method according to various formulation forms, patient age, gender and other conditions, degree of disease, and the like. Or administered. For example, tablets, pills, solutions, suspensions, emulsions, granules, and capsules are orally administered.
  • the dose of the preparation of the present invention is appropriately selected depending on the usage, age of the patient, gender, other conditions, the degree of the disease, and the like.In general, the amount of the active ingredient compound is expressed as It is preferred that the amount be about 11 to 200 mg. In addition, it is preferable that the preparation is usually administered in 1 to 3 divided doses.
  • the antiviral composition of the present invention exhibits an excellent antiviral effect of selectively inactivating virus-infected cells, and has extremely low toxicity and excellent safety. is there. Further, the active ingredient such as the antiviral composition of the present invention is excellent in solubility in water and excellent in absorbability of intestinal tract. Further, the antiviral composition of the present invention And the like have the effect of selectively inactivating virus-infected cells, so that their formulation or administration can be extremely small.
  • the shape, form and the like are not particularly limited, and they can be arbitrarily designed.
  • a novel antiviral composition effective for prevention and treatment of viral infections caused by various viruses such as AIDS virus
  • an antiviral function is added.
  • (3) can provide an antiviral drug effective against infectious diseases caused by viruses such as AIDS virus, and (4) can provide virus-infected cells.
  • New evil (1Z2I) that can be selectively deactivated
  • the present invention will be specifically described by an IHN virus infection suppression test.
  • a MEM medium minimum essential nutrient medium containing 1 ⁇ g / ml3 ⁇ 4V and 10 ⁇ g Zml of tea catechin was inoculated with 2 cells of RTG-2 cells derived from dimasu, and 0.1 I / cell was added to each cell.
  • the cells were infected with the HN virus (moiO.1) and cultured at 15 ° C and pH 7.2 for 5 to 10 days. After the culture, the number of viruses (virus titer TCID Zml) was measured using the culture supernatant. That
  • a MEM medium minimum essential nutrient medium containing 1 ⁇ gZml of humic acid and 10 ⁇ gZml of humic acid was inoculated with RTG-2 cultured cells derived from dimasu, and 0.01 IHN / cell was further added.
  • the virus (moiO.01) was infected and cultured at 15 ° C., pH 7.2 for 7 days. After the culture, the number of viruses (virus titer TCID / ml) was measured using the culture supernatant. Table 2 shows the results.
  • Two 60-liter aquariums contain 220 juvenile salmon trout with an average weight of 0.5 g, and feed humic acid and humic acid to one juvenile while supplying breeding water (groundwater) at 10 ° C at a rate of 2 liters Z.
  • the Nal-mixed diet was fed, while the other fry were fed a normal diet without them as a control.
  • Mixing 5 mg of humic acid and 50 mg of NaI per 100 g of small granular feed and coating with 5 g of feed oil prevents dissolution and diffusion of reagents into water.
  • a solution containing the IHN virus (virus solution) was adjusted through a micropump to a virus count (virus titer) of 100 TCID Zml in breeding water, bred for 5 days, and infected with the virus.
  • Bait virus count
  • Two 60-liter aquariums hold 220 juvenile salmon trout with an average weight of 0.3 g, and supply humic acid and humic acid to one juvenile while feeding breeding water (groundwater) at 10 ° C at a rate of 2 liters Z.
  • breeding water groundwater
  • the Nal-mixed diet was fed, while the other fry were fed a normal diet without them as a control.
  • Mixing 5 mg of humic acid and 50 mg of NaI per 100 g of small granular feed and coating with 5 g of feed oil prevents dissolution and diffusion of reagents into water.
  • a solution containing the IHN virus (virus solution) was adjusted through a micropump to a virus count (virus titer) of 100 TCID Zml in breeding water, bred for 5 days, and infected with the virus.
  • Two 60-liter aquariums contain 220 fish salmon fry, averaging 0.6-0.9 g in weight, and feed breeding water (groundwater) at 10 ° C at a rate of 2 liters Z to one fry. Food mixed with humic acid and Nal was not mixed with the other fry as a control! Normal feed was given. A mixture of 10 mg of humic acid and NallOmg per 100 g of small granular feed was coated with 5 g of feed oil to prevent the reagent from dissolving and diffusing into water. A solution containing IHN virus (virus solution) is passed through a micropump and the number of viruses (virus titer) 100TCID
  • a toxicity test was performed.
  • Two 60-liter aquariums contain 220 fish salmon fry, averaging 0.3 g in weight, and feed breeding water (groundwater) at 10 ° C at a rate of 2 liters Z while humic acid and The Nal-mixed diet was given, while the other fry were given normal diet without control as a control.
  • Figure 7 shows the results. You.
  • the cells were added after being adjusted (PH 7.4) with a culture medium, and further inoculated with an avian influenza virus solution whose virus titer had been measured in advance, and cultured at 37 ° C for 3-5 days.
  • CPE Cytopathic effect
  • Test Example 9 A microplate is inoculated with 30 ⁇ L of chicken fetal fibroblast cell suspension X 10 5 cells Zml), and the cell culture medium is adjusted to a prescribed concentration of Nal and green tea catechin (main component: epigallocatechin gallate). 37. Adjusted pH (pH 7.4) and spiked, then inoculated with a solution of Avian Newcastle disease virus whose virus titer had been measured in advance. C. The cells were cultured for 35 days.
  • CPE Cytopathic effect
  • a microplate is inoculated with 30 ⁇ L / well of MDBK cell suspension (1 ⁇ 10 5 cells Zml) of Nishi and green tea catechin (main component: epigallocatechin gallate) at a specified concentration.
  • Cell culture medium pH 7.4
  • a microplate is inoculated with 30 L / well of a feline renal fibroblast suspension (1 ⁇ 10 5 cells / ml), and Nal and green tea catechin (main component: epigallocatechin gallate) are in a prescribed concentration.
  • the cells were adjusted with cell culture medium (PH 7.4), added, and inoculated with a feline virulent virus solution whose virus titer had been measured in advance, and cultured at 37 ° C for 3-5 days.
  • CPE Cytopathic effect
  • the present invention relates to an antiviral composition and the like, and according to the present invention, a novel antiviral composition which is extremely effective in preventing and treating infectious diseases caused by viruses such as AIDS virus.
  • Functional foods having antiviral functions, antiviral preparations, etc. can be manufactured and provided. It is possible to provide a novel antiviral drug having an action of selectively inactivating virus-infected cells.
  • a functional food to which an anti-HIV virus activity is added can be provided.
  • Elucidation of the mechanism of cell death in various virus-infected cells and the pathogenesis of new virus infections can be achieved by utilizing the principle of the present invention, which uses the "degeneration system using eodoion in virus-infected cells". It can contribute to the establishment of an evaluation method. Since the antiviral preparation of the present invention is inexpensive and highly safe, it is possible to quickly and urgently respond to and contribute to AIDS relief activities in South Africa and the like by using the antiviral preparation. it can. Brief Description of Drawings
  • FIG. 1 shows a top view and a cross-sectional view of an electrophoresis apparatus used in a test example of the present invention.
  • FIG. 2 shows an electrophoretogram of virus-infected RTG- 2 cells.
  • FIG. 3 shows electropherograms of RTG-2 cells and CHSE-214 cells.
  • FIG. 4 shows the results of an oral administration test to juvenile salmon in Test Example 4.
  • FIG. 5 shows the results of an oral administration test to juvenile salmon trout in Test Example 5.
  • FIG. 6 shows the results of an oral administration test to juvenile salmon trout in Test Example 6.

Abstract

An antiviral composition having an effect of selectively inactivating virus-infected cells which comprises, as the active ingredient, iodine ion or a compound forming iodine ion; a functional food containing the antiviral composition as described above and thus having an antiviral function imparted thereto; and an antiviral drug comprising the antiviral composition as described above and having an effect of selectively inactivating virus-infected cells. Thus, it is intended to provide a novel antiviral composition and so on having a function of selectively inactivating AIDS virus-infected cells, viral cancer cells, etc.

Description

明 細 書  Specification
抗エイズウイルス性組成物及びウィルス感染細胞の選択的不活化方法 技術分野  TECHNICAL FIELD The present invention relates to an anti-AIDS virus composition and a method for selectively inactivating virus-infected cells.
[0001] 本発明は、エイズウイルス等に優れた抗ウィルス作用を発揮する抗ウィルス性組成 物等に関するものであり、更に詳しくは、エイズウイルス等のウィルスに感染したウイ ルス感染細胞を選択的に不活ィ匕する機能を有する抗ウィルス性組成物、当該抗ウイ ルス性を付加した機能性食品、及び抗ウィルス薬剤に関するものである。本発明は、 エイズウイルス等の各種ウィルスの感染によるウィルス性疾患に適用される抗ウィル ス製剤等の技術分野において、生体細胞系におけるウィルス感染細胞を選択的に 不活化し、死滅させる作用を有する新 ヽ抗ウィルス性組成物及びその用途を提供 するものであり、例えば、エイズウイルス感染細胞、ウィルス性ガン細胞等を選択的に 不活化させ、これらの疾患の予防、治療薬、及び機能性食品等として有用な新規医 薬品及び機能性食品等を提供するものである。  The present invention relates to an antiviral composition exhibiting an excellent antiviral action against an AIDS virus or the like, and more particularly, to a virus-infected cell infected with a virus such as an AIDS virus. The present invention relates to an antiviral composition having an inactivating function, a functional food to which the antiviral property is added, and an antiviral drug. INDUSTRIAL APPLICABILITY The present invention has an effect of selectively inactivating and killing virus-infected cells in a living cell system in a technical field such as an antiviral preparation applied to a viral disease caused by infection of various viruses such as an AIDS virus. The present invention provides an antiviral composition and a use thereof. For example, the present invention selectively inactivates AIDS virus-infected cells, viral cancer cells, etc., and prevents, treats, and functional foods for these diseases. It is intended to provide useful new drugs and functional foods.
背景技術  Background art
[0002] 現在、アフリカ地区では、最大 20%の一般市民がエイズに感染しているとの調査も あり、これらの国における患者の救済は、非常に重要かつ緊急性の高い問題となつ ている。 WHOが、現時点における最高の治療薬であるカクテル剤を無償供与してい る力 その数には限りがあり、南アフリカ地区では、日々数百人単位で死亡者が発生 しており、その大部分は小児である。現時点で有望性のある薬剤の開発が種々行な われているが、薬事法、医師法などの制約により、臨床試験を経ずに投与することは 禁止されているため、現状では、有望な化学物質ゃ抗ウィルス性物質が開発されて も(特許文献 1一 2)、これらをすぐに使用することはできないという問題がある。  [0002] At present, up to 20% of civilians in the African region are infected with AIDS, and rescue of patients in these countries is a very important and urgent issue. . WHO's ability to provide free cocktails, the best therapeutics available at present, is limited in number, with hundreds of deaths occurring daily in the South African region, most of which I'm a child. At present, various promising drugs are being developed.However, due to restrictions such as the Pharmaceutical Affairs Law and the Physician Law, it is prohibited to administer drugs without going through clinical trials. Substances—Even if antiviral substances are developed (Patent Documents 1-2), there is a problem that they cannot be used immediately.
[0003] 一方、我が国の状況についても、国外力 侵入する各種ウィルス、例えば、エイズ、 脾炎、 SARS、エボラ等の出現で、ウィルス感染の危険にさらされている現在、侵入 ウィルスの防除には、ウィルスのレベルを発病濃度以下に押さえる方法を準備するこ とが肝要である。その方法は、簡便、安価かつ国民全般に受け入れられるものでなけ ればならず、例えば、食品を介するやり方は合目的であると考えられている。また、こ のことは、国民病になりつつあるガンについても共通することである。 [0003] On the other hand, regarding the situation in Japan, the emergence of various viruses that invade foreign countries, for example, AIDS, spleenitis, SARS, Ebola, etc., has put them at risk of virus infection. It is important to prepare a method to keep the virus level below the onset level. The method must be simple, inexpensive and generally accepted by the general public. For example, food-based methods are considered to be suitable. Also this The same is true of cancer, which is becoming a national disease.
[0004] このように、各種ウィルス感染、特に、エイズウイルス感染の問題を中心として、各種 ウィルス感染に対する予防及び防除の問題は、グローバルィ匕を迎えた今日における 国際的な重要課題となっており、特に、途上国において、緊急の対策が求められて いる。しかし、実際には、低コストで、し力も、高い治療効果が期待できる有効な治療 薬が少ないのが現状であり、当技術分野においては、エイズウイルス感染細胞ゃガ ン細胞を選択的に不活化し、死滅させることが可能な新しい治療薬や機能性食品等 の開発が急務の課題として強く要請されていた。  [0004] As described above, the problem of prevention and control of various virus infections, especially the problem of AIDS virus infection, has become an important international issue today with the arrival of Globali Dani. Urgent action is required, especially in developing countries. However, in reality, there are few effective therapeutic agents that can be expected to have a high therapeutic effect at low cost and have a high therapeutic effect. In the art, AIDS virus-infected cells and cancer cells cannot be selectively selected. The development of new therapeutic agents and functional foods that could be activated and killed was urgently required.
[0005] 特許文献 1:特開平 5— 294838号公報  [0005] Patent Document 1: Japanese Patent Laid-Open No. 5-294838
特許文献 2:特開 2002— 293803号公報  Patent Document 2: Japanese Patent Application Laid-Open No. 2002-293803
発明の開示  Disclosure of the invention
発明が解決しょうとする課題  Problems to be solved by the invention
[0006] このような状況の中で、本発明者らは、上記従来技術に鑑みて、低コストで、し力も 安全性が高ぐエイズウイルス等の各種ウィルスによるウィルス感染症の予防、治療 に有効な新し ヽ機能性食品ゃ抗ウィルス製剤等を開発することを目標として鋭意研 究を積み重ねた結果、ョードイオンを使用したウィルス感染細胞における、本発明者 らが開発した新しいョード供給システムを利用することにより、所期の目的を達成し得 ることを見出し、更に研究を重ねて、本発明を完成するに至った。  [0006] Under such circumstances, the present inventors have considered in view of the above-mentioned prior art that prevention and treatment of viral infectious diseases caused by various viruses such as the AIDS virus, which is low in cost and highly safe, can be performed. As a result of intensive research aimed at developing effective new ヽ functional foods ゃ antiviral preparations, etc., we used the new eodo supply system developed by the present inventors for virus-infected cells using eodo ions. As a result, the present inventors have found that the intended purpose can be achieved, and have conducted further studies to complete the present invention.
[0007] 即ち、本発明は、エイズウイルス感染細胞等のウィルス感染細胞におけるョードィ オンを使用したョード供給システムを利用して、当該ウィルス感染細胞を選択的に不 活化する特異的な抗ウィルス作用を発揮する、新しい抗ウィルス性組成物、当該抗ゥ ィルス組成物を配合した機能性食品、及び抗ウィルス薬剤等を提供することを目的と するものである。  [0007] That is, the present invention provides a specific antiviral effect of selectively inactivating virus-infected cells by utilizing an eodo-supply system using oodoion in virus-infected cells such as AIDS virus-infected cells. It is an object of the present invention to provide a novel antiviral composition, a functional food containing the antiviral composition, an antiviral drug, and the like.
課題を解決するための手段  Means for solving the problem
[0008] 上記課題を解決するための本発明は、以下の技術的手段から構成される。 [0008] The present invention for solving the above-mentioned problems includes the following technical means.
( 1)ョードイオン又はョードイオンを生成する化合物を有効成分として含むことを特徴 とするウィルス感染細胞を選択的に不活性化する作用を有する抗ウィルス性組成物 (2)ョードイオンとポリフエノールイ匕合物を組み合わせた前記(1)に記載の抗ウィルス 性組成物。 (1) An antiviral composition having an action to selectively inactivate virus-infected cells, characterized by containing as an active ingredient an ore ion or a compound that produces an ore ion. (2) The antiviral composition according to the above (1), wherein the antiviral composition is a combination of an anode ion and a polyphenol conjugate.
(3)前記(1)又は(2)に記載の抗ウィルス性組成物を配合して抗ウィルス機能を付加 したことを特徴とする抗ウィルス機能を有する機能性食品。  (3) A functional food having an antiviral function, wherein the antiviral composition according to the above (1) or (2) is blended to add an antiviral function.
(4)前記(1)又は(2)に記載の抗ウィルス性組成物からなることを特徴とするウィルス 感染細胞を選択的に不活性化する作用を有する抗ウィルス薬剤。  (4) An antiviral drug having an action of selectively inactivating virus-infected cells, comprising the antiviral composition according to (1) or (2).
(5)ョードイオン又はョードイオンを生成する化合物をウィルス感染細胞を含む生体 細胞系に供給して、ウィルス感染細胞内に特異的にョード(1Z2I )を生成させ、当  (5) Supplying an oluded ion or a compound that produces an iodine ion to a living cell system containing a virus-infected cell to specifically produce an eodo (1Z2I) within the virus-infected cell,
2  2
該ョード(1Z2I )の作用によりウィルス感染細胞を選択的に不活ィ匕させ、死滅させる  The virus (1Z2I) acts to selectively inactivate and kill virus-infected cells.
2  2
ことを特徴とするウィルス感染細胞の選択的不活化方法。  A method for selectively inactivating virus-infected cells, comprising:
(6)ョードイオン又はョードイオンを生成する化合物をウィルス感染細胞を含む生体 細胞系に供給して、ウィルス感染細胞内に特異的にョード(1Z2I )を生成させること  (6) Supplying an ode ion or a compound generating an ode ion to a living cell system containing a virus-infected cell to specifically produce an ode (1Z2I) in the virus-infected cell.
2  2
を特徴とするウィルス感染細胞における選択的ョード(1Z2I )生成 'デリバティブシ  Selective pseudo (1Z2I) generation in virus-infected cells characterized by
2  2
ステム。  Stem.
[0009] 次に、本発明について、更に詳細に説明する。  Next, the present invention will be described in more detail.
本発明の抗ウィルス性組成物は、ョードイオン又はョードイオンを生成する化合物 を有効成分として含有することを特徴とするものであり、本発明は、ョードイオン又は ョードイオンを生成する化合物をウィルス感染細胞を含む生体細胞系に供給してウイ ルス感染細胞において、特異的にョード(1Z2I )を生成させるョード(1Z2I )生成- The antiviral composition of the present invention is characterized in that it contains, as an active ingredient, an ode ion or a compound that generates an ode ion. Ode (1Z2I) production to supply specifically to cell lines to produce eodo (1Z2I) in virus-infected cells-
2 2 デリパテイブシステムを利用して、ウィルス感染細胞を選択的に不活ィ匕させ、死滅さ せることを特徴とする抗ウィルス製剤、抗ウィルス機能を有する機能性食品等を提供 するものである。 22 Provide anti-viral preparations, functional foods with anti-viral function, etc., which are characterized by selectively inactivating and killing virus-infected cells using a derivative system. is there.
[0010] 本発明は、本発明者らが見出した以下のような新規知見;(1)ョードイオン水の電 解により陽極サイドにョードの生成が認められたこと; Γ→[·Ι]→1Ζ2Ι、(2)生細胞  [0010] The present invention provides the following novel findings discovered by the present inventors; (1) generation of eaves on the anode side due to electrolysis of ionic ion water; Γ → [· Ι] → 1Ζ2Ι , (2) live cells
2  2
の無担体電気泳動(ろ紙やゲルを使用せずに細胞を浮遊状態のまま電気泳動する 方法)で、正常細胞の分布中心は中性の ±0、 ΙΗΝウィルス感染細胞の分布中心は マイナスサイドにシフトし、細胞膜内面 (細胞質)電荷はプラスになることが認められた こと、(3) ΙΗΝ (サケマスに感染する伝染性造血器壊死症ウィルス)感染細胞内のョ ードイオンは、上記(1)と類似の環境であるが故に、脱電子されてョードを生成するこ と力 S認められたこと、(4)感染細胞内ョードが、ウィルス、ないし細胞を不活化すること が認められたこと、に基づいて創出されたものである。 In the method of carrier-free electrophoresis (electrophoresis with cells suspended without using filter paper or gel), the distribution center of normal cells is neutral ± 0, and the distribution center of virus-infected cells is on the minus side. (3) ΙΗΝ (infectious hematopoietic necrosis virus that infects salmon) infected cells The mode ion has been found to be deelectronized to produce eodes because it has an environment similar to (1) above, and (4) the inodes in infected cells inactivate viruses or cells. It was created based on the fact that it was recognized.
[0011] ここで、上記知見を得た実験系につ 、て説明する。図 1に、生体組織の生細胞の無 担体電気泳動に用い装置の一例を示す。図中、 aはアノード(白金)、 bはアノード端 末のコネクション、 cは力ソード(白金)、 eはフィルター紙部、 fは細胞の拡散を防ぐフィ ルター紙部、 gはバッファー、 hは電気泳動後に、装置の電気泳動タンクを 9個の小室 (八〔=ァノード〕4、八3、八2、八1、3〔=サンプル〕、。〔=カソード〕1、 C2、 C3、 C4) に分ける手段を装着させるための磁気フェライトーラバー部、 iは電気泳動に装置を分 けるために用いるプラスチック板、である。試験の間、装置は、魚細胞に対して 15°C に、又は動物細胞に対して 37°Cにコントロールした。矢印は、断面の位置を示す。 Here, an experimental system that has obtained the above findings will be described. FIG. 1 shows an example of an apparatus used for carrier-free electrophoresis of living cells of a living tissue. In the figure, a is the anode (platinum), b is the connection of the anode terminal, c is the force sword (platinum), e is the filter paper, f is the filter paper that prevents cell diffusion, g is the buffer, and h is the buffer. After electrophoresis, the electrophoresis tank of the device was replaced with 9 compartments (8 [= node] 4, 83, 82, 81, 3 [= sample], [= cathode] 1, C2, C3, C4) A magnetic ferrite rubber part for mounting means for dividing into two parts, i is a plastic plate used for separating the apparatus into electrophoresis. During the test, the device was controlled at 15 ° C for fish cells or 37 ° C for animal cells. The arrow indicates the position of the cross section.
[0012] 図 2に、ウィルスを感染させた RTG— 2細胞(-ジマスの生殖腺カゝら採取した培養可 能な細胞で、 IHNウィルス等の宿主培養細胞)の電気泳動図を示す。これらは、ウイ ルス感染 RTG— 2細胞の電気泳動図であり、図中、(A)では、 IHNウィルス感染後 1 日で MEMで 15°Cで電気泳動を行い、(B)では、同感染後 3日で電気泳動を行い、 (C)では、同感染後 5日で g—strophantin又は sodium azideを添カ卩して、 MEM で電気泳動を行い、(D)では、同感染後 5日で MEMで 15°Cで電気泳動を行い、(E )では、 IPNウィルス感染細胞を用いて、感染後 1日で MEMで電気泳動を行い、 (F )では、 IPNウィルス感染細胞を用いて、感染後 1日で g—strophantin又は sodium azideを添カ卩して、 MEMで電気泳動を行った結果を示す。  FIG. 2 shows an electrophoretic diagram of virus-infected RTG-2 cells (cultivable cells collected from germ-line glands of -mouth trout and cultured host cells of the IHN virus or the like). These are electropherograms of virus-infected RTG-2 cells. In (A), electrophoresis was performed at 15 ° C in MEM one day after infection with the IHN virus. Electrophoresis was performed 3 days later. In (C), g-strophantin or sodium azide was added 5 days after the infection and electrophoresis was performed in MEM. In (D), electrophoresis was performed 5 days after the infection. In (E), the cells were electrophoresed at 15 ° C in MEM. In (E), the cells were electrophoresed in MEM one day after infection. In (F), the cells were infected with IPN virus. One day after infection, g-strophantin or sodium azide was added, and the results of electrophoresis with MEM are shown.
[0013] また、図 3に、生RTG—2細胞及びCHSE—214細胞(マス(マスノスケ)から採取し た培養可能な細胞で、 IHNウィルス等の宿主培養細胞)の電気泳動図を示す。これ らは、 107個 Zlmlの RTG— 2細胞又は CHSE— 214細胞を電気泳動装置の中央に カロえて、(A)では、細胞を電流をカ卩えないで、 EBSSで pH7. 0で 15分間静置し、(B )では、 EBSSで pHpH7. 0で電気泳動(DCで 20mA、 15分)を行い、(C)では、ゥ シ胎児血清及びマス血清を 10%加えて、 EBSSで pH7. 0で電気泳動を行った結果 を示す。これらから、生細胞の無担体電気泳動で、正常細胞の分布中心は中性の士 0、また、 IHNウィルス感染細胞の分布中心はマイナスサイドにシフトし、細胞膜面( 細胞質)電荷はプラスになることが分かる。これらの細胞にョードイオンを供給すると、 IHN感染細胞内のョードイオンは、脱電子されてョードを生成し、このョードの殺菌 作用により感染細胞が選択的に不活化される。 [0013] FIG. 3 shows electropherograms of live RTG-2 cells and CHSE-214 cells (culturable cells collected from trout (masunosuke) and host culture cells of IHN virus or the like). These cells show that 107 Zlml of RTG-2 cells or CHSE-214 cells were calored in the center of the electrophoresis apparatus. After standing, in (B), electrophoresis (20 mA, 15 minutes in DC) was performed with EBSS at pH pH 7.0. The results of electrophoresis at 0 are shown. From these results, in carrier-free electrophoresis of living cells, the distribution center of normal cells was neutral and the distribution center of IHN virus-infected cells shifted to the minus side, and the cell membrane surface ( It can be seen that the (cytoplasmic) charge is positive. When these cells are supplied with iodide ions, the iodide ions in the IHN-infected cells are de-electronized to produce eodo, and the infected cells are selectively inactivated by the bactericidal action of the eodo.
[0014] 本発明では、ョードイオン又はョードイオンを生成する化合物として、例えば、 Γ 、 Nalが例示されるが、これらに制限されるものではなぐョードオンを生成する化合物 であれば同様に使用することができる。また、本発明では、ョードイオンにポリフエノー ル化合物、例えば、フミン酸、茶力テキン等を組み合わせることで、更に、抗ウィルス 活性を高めることができる。本発明では、特に、 Nalとフミン酸及び/又はカテキンを 組み合わせて使用することが好ましい。本発明では、これらの化合物を、例えば、薬 学的に許容される担体と組み合わせることで、抗ウィルス性組成物とすることができる 。また、この抗ウィルス性組成物を任意の食品に配合することにより、抗ウィルス機能 を付加した機能性食品とすることができる。更に、この抗ウィルス性組成物を利用して 、抗ウィルス薬剤とすることができる。  [0014] In the present invention, examples of ョ and Nal are given as examples of 化合物 or Nal as a compound that produces ョ or ion, but any compound that produces オ ン can be used as long as it is not limited to these. . Further, in the present invention, the antiviral activity can be further enhanced by combining a polyphenol compound such as humic acid, tea power techin, or the like with the anode. In the present invention, it is particularly preferable to use Nal in combination with humic acid and / or catechin. In the present invention, an antiviral composition can be prepared by combining these compounds with, for example, a pharmaceutically acceptable carrier. In addition, by blending this antiviral composition with any food, a functional food having an antiviral function can be obtained. Further, the antiviral composition can be used as an antiviral drug.
[0015] 本発明では、後記する試験例に示されるように、強力な魚病発症性の IHNウィルス  [0015] In the present invention, as shown in the test examples described later, a strong fish disease-causing IHN virus
(RNA系)培養系に対し、その力価を有意に下げ、また、サクラマス感染試験におい ても有意に高 、生残率を示したョードナトリウム Zポリフエノール (茶カテキン又はフミ ン酸等)は、抗ウィルス性機能を有することが示された。何れの物質もありふれたもの であり、食して当該機能が発現される点が特に注目に値する。本発明の原理を利用 して、例えば、細胞の無担体電気泳動における正味電荷をマーカーに、また、中性 電荷を正常点に各々設定して、中性点力 の正 ·負の電荷シフトを細胞の代謝異常 性の尺度として、検体細胞を生きたまま電気泳動装置で分画し、その分布を測定す ることが可能となる。また、当該細胞系の正味電荷が正常点に回帰する物質をスクリ 一二ングすることにより、細胞異常を制御する効能成分を特定することができる。また Compared to (RNA-based) cultures, sodium eodo-sodium Z polyphenols (such as tea catechin or humic acid), which significantly reduced the titer and showed a significantly higher survival rate in the salmon infection test, It has been shown to have antiviral function. It is particularly noteworthy that both substances are commonplace and that the function is manifested when eaten. Utilizing the principle of the present invention, for example, a net charge in carrier-free electrophoresis of a cell is set as a marker, and a neutral charge is set at a normal point, and a positive / negative charge shift of a neutral point force is calculated. As a measure of the metabolic abnormalities of cells, it is possible to fractionate sample cells alive using an electrophoresis apparatus and measure their distribution. In addition, by screening a substance whose net charge of the cell system returns to a normal point, an active ingredient that controls cell abnormalities can be specified. Also
、当該特定物質を、魚類系(細胞、稚魚)で評価することにより、低コストで高精度の 性能評価を行うことが可能となる。更に、生きた細胞の異常 Z正常を、その電荷の測 定で代謝の異常を検出することができる。本発明のシステムは、これらの評価方法を 確立することを可能にする方法としても注目に値する。 By evaluating the specific substance in a fish system (cells, fry), it is possible to perform low-cost and high-precision performance evaluation. Furthermore, abnormalities in living cells can be detected as normal and abnormalities in metabolism can be detected by measuring the charge. The system of the present invention is also noteworthy as a method that makes it possible to establish these evaluation methods.
[0016] 本発明の抗ウィルス性組成物中に配合されるべきョードイオン又はョードイオンを 生成する化合物の配合量としては、本発明の所期の効果が発現される量である限り[0016] Ode ions or olude ions to be incorporated into the antiviral composition of the present invention The amount of the compound to be produced is as long as the desired effect of the present invention is exhibited.
、特に限定されるものではないが、通常、本発明の組成物中に 0. 01— 10重量%程 度配合することが好ましい。本発明の抗ウィルス性組成物は、製剤で通常使用される 充填剤、増量剤、結合剤、付湿剤、崩壊剤、表面活性剤、及び滑沢剤等の希釈剤あ るいは賦形剤を用いて調製される。この組成物の形態としては、治療目的に応じて選 択でき、その代表的なものとして、錠剤、丸剤、散剤、液剤、懸濁剤、乳剤、顆粒剤、 カプセル剤、及び注射剤 (液剤、懸濁剤等)等が例示される。 Although not particularly limited, it is usually preferable to add 0.01 to 10% by weight to the composition of the present invention. The antiviral composition of the present invention may contain diluents or excipients such as fillers, bulking agents, binders, humectants, disintegrants, surfactants, and lubricants which are usually used in pharmaceutical preparations. It is prepared using The form of this composition can be selected according to the purpose of treatment, and typical examples include tablets, pills, powders, solutions, suspensions, emulsions, granules, capsules, and injections (solutions). , Suspending agents, etc.).
[0017] 本発明の組成物には、慣用の添加物、例えば、ビタミン剤、ホルモン剤、アミノ酸等 の薬効剤、界面活性剤、色素、染料、顔料、香料、紫外線吸収剤、保湿剤、増粘剤、 酸化防止剤、金属封鎖剤、及び pH調整剤等を必要に応じて任意に配合することが できる。本発明において、担体としては、例えば、ブドウ糖、乳糖、デンプン、カカオ 脂、硬化植物油、カオリン、タルク等の賦形剤、アラビアゴム末、トラガント末、ゼラチ ン、及びエタノール等の結合剤、ラミナラン、及びカンテン等の崩壊剤等を使用する ことができる。注射剤として使用される場合、溶剤、乳剤及び懸濁液は殺菌され、か つ血液と等張であることが好ましい。これらの形態にするに際して、希釈剤として、例 えば、水、エチルアルコール、プロピレングリコール、及びポリオキシエチレンソルビタ ン脂肪酸エステル等を使用することができる。  [0017] The composition of the present invention may contain conventional additives such as vitamins, hormonal agents, pharmacologic agents such as amino acids, surfactants, pigments, dyes, pigments, fragrances, ultraviolet absorbers, humectants, and humectants. A tackifier, an antioxidant, a sequestering agent, a pH adjuster, and the like can be arbitrarily added as necessary. In the present invention, examples of the carrier include excipients such as glucose, lactose, starch, cocoa butter, hydrogenated vegetable oil, kaolin, and talc; binders such as gum arabic, tragacanth, gelatin, and ethanol; laminaran; And disintegrating agents such as agar. When used as an injection, the solvents, emulsions and suspensions are preferably sterile and isotonic with blood. In making these forms, for example, water, ethyl alcohol, propylene glycol, polyoxyethylene sorbitan fatty acid ester and the like can be used as the diluent.
[0018] 本発明の抗ウィルス性組成物ないしその薬剤の配合方法、投与方法は、特に制限 はなぐ各種製剤形態、患者の年齢、性別その他の条件、疾患の程度等に応じた方 法で配合又は投与される。例えば、錠剤、丸剤、液剤、懸濁剤、乳剤、顆粒剤及び力 プセル剤の場合には、経口投与される。本発明の製剤の投与量は、用法、患者の年 齢、性別、その他の条件、疾患の程度等により適宜選択されるが、通常、有効成分化 合物の量が、一日当たり体重 lKg当たり、約 1一 200mg程度とすることが好適である 。また、この製剤は、通常 1一 3回に分けて投与することが好ましい。  [0018] The compounding method and administration method of the antiviral composition or the drug thereof of the present invention are not particularly limited, and are compounded by a method according to various formulation forms, patient age, gender and other conditions, degree of disease, and the like. Or administered. For example, tablets, pills, solutions, suspensions, emulsions, granules, and capsules are orally administered. The dose of the preparation of the present invention is appropriately selected depending on the usage, age of the patient, gender, other conditions, the degree of the disease, and the like.In general, the amount of the active ingredient compound is expressed as It is preferred that the amount be about 11 to 200 mg. In addition, it is preferable that the preparation is usually administered in 1 to 3 divided doses.
[0019] 本発明の抗ウィルス性組成物は、ウィルス感染細胞を選択的に不活化するという、 優れた抗ウィルス作用を発現し、しカゝも毒性は極めて低ぐ安全性に優れたものであ る。また、本発明の抗ウィルス性組成物等の有効成分は、水に対する溶解性に優れ ており、腸管力ゝらの吸収性に優れたものである。更に、本発明の抗ウィルス性組成物 等は、ウィルス感染細胞を選択的に不活ィ匕させる作用を有するので、その配合ない し投与を極めて少量にすることができる。本発明の上記抗ウィルス性組成物を食品 原料な!/、し加工食品に配合することで、抗ウィルス機能を付加した機能性食品を製 造することができるが、食品原料ないし加工食品の種類、形態等は特に制限されるも のではなぐこれらは、任意に設計することができる。 [0019] The antiviral composition of the present invention exhibits an excellent antiviral effect of selectively inactivating virus-infected cells, and has extremely low toxicity and excellent safety. is there. Further, the active ingredient such as the antiviral composition of the present invention is excellent in solubility in water and excellent in absorbability of intestinal tract. Further, the antiviral composition of the present invention And the like have the effect of selectively inactivating virus-infected cells, so that their formulation or administration can be extremely small. By blending the above antiviral composition of the present invention with food raw materials and / or processed foods, functional foods with an added antiviral function can be produced. The shape, form and the like are not particularly limited, and they can be arbitrarily designed.
発明の効果  The invention's effect
[0020] 本発明により、(1)エイズウイルス等の各種ウィルスによるウィルス感染症の予防、 治療に有効な新 ヽ抗ウィルス性組成物を提供することができる、 (2)抗ウィルス機 能を付加した機能性食品を提供できる、(3)低コストで、簡便な方法で製造及び利用 できる、エイズウイルス等のウィルスによる感染症に有効な抗ウィルス薬剤を提供でき る、(4)ウィルス感染細胞を選択的に不活ィ匕することが可能な新しいョード(1Z2I )  According to the present invention, (1) a novel antiviral composition effective for prevention and treatment of viral infections caused by various viruses such as AIDS virus can be provided, and (2) an antiviral function is added. (3) can provide an antiviral drug effective against infectious diseases caused by viruses such as AIDS virus, and (4) can provide virus-infected cells. New evil (1Z2I) that can be selectively deactivated
2 生成 ·デリパテイブシステムを提供できる、と ヽぅ格別の効果が奏される。  2 Generation ・ Delivery system can be provided.
発明を実施するための最良の形態  BEST MODE FOR CARRYING OUT THE INVENTION
[0021] 次に、試験例及び実施例に基づいて本発明を具体的に説明するが、本発明は、以 下の事例によって何ら限定されるものではない。 Next, the present invention will be specifically described based on test examples and examples, but the present invention is not limited at all by the following examples.
[0022] まず、 IHNウィルス感染抑制試験により、本発明を具体的に説明する。 First, the present invention will be specifically described by an IHN virus infection suppression test.
試験例 1  Test example 1
本試験例では、茶カテキンの抗ウィルス (IHN ウィルス)効果につ!、て試験した。 1 μ g/ml¾V、し 10 μ gZmlの茶カテキンを含む MEM培地(最小必須栄養培地) に、 -ジマス由来の培養細胞 RTG— 2細胞を接種し、更に、一細胞当たり 0. 1個の I HNウィルス(moiO. 1)を感染させ、 15°C、 pH7. 2で、 5日ないし 10日間培養した。 培養後、ウィルス数 (ウィルス力価 TCID Zml)を培養上清を用いて測定した。その  In this test example, the antiviral (IHN virus) effect of tea catechin was tested. A MEM medium (minimum essential nutrient medium) containing 1 μg / ml¾V and 10 μg Zml of tea catechin was inoculated with 2 cells of RTG-2 cells derived from dimasu, and 0.1 I / cell was added to each cell. The cells were infected with the HN virus (moiO.1) and cultured at 15 ° C and pH 7.2 for 5 to 10 days. After the culture, the number of viruses (virus titer TCID Zml) was measured using the culture supernatant. That
50  50
結果を表 1に示す。  The results are shown in Table 1.
[0023] [表 1] ウィルス力価 ( l o g 1 () T C I D5(1/m 1 ) [Table 1] Virus titer (log 1 () TCID 5 (1 / m 1)
Figure imgf000010_0001
Figure imgf000010_0001
[0024] 試験例 2 [0024] Test Example 2
本試験例では、フミン酸の抗ウィルス (IHNウィルス)効果にっレ、て試験した。  In this test example, the antiviral (IHN virus) effect of humic acid was tested.
1 μ gZmlなレヽし 10 μ gZmlのフミン酸を含む MEM培地(最小必須栄養培地)に 、 -ジマス由来の培養細胞 RTG— 2細胞を接種し、更に、一細胞当たり 0. 01個の IH Nウィルス (moiO. 01)を感染させ、 15°C、 pH7. 2で、 7日間培養した。培養後、ウイ ルス数 (ウィルス力価 TCID /ml)を培養上清を用いて測定した。その結果を表 2に  A MEM medium (minimum essential nutrient medium) containing 1 μgZml of humic acid and 10 μgZml of humic acid was inoculated with RTG-2 cultured cells derived from dimasu, and 0.01 IHN / cell was further added. The virus (moiO.01) was infected and cultured at 15 ° C., pH 7.2 for 7 days. After the culture, the number of viruses (virus titer TCID / ml) was measured using the culture supernatant. Table 2 shows the results.
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示す。  Show.
[0025] [表 2] ウィルス力価 ( l o g i。 T C I D5。ノ m l ) [Table 2] Virus titer (logi. TCID 5 ; ml)
Figure imgf000010_0002
Figure imgf000010_0002
[0026] 試験例 3 [0026] Test Example 3
本試験例では、茶カテキンな!/、しフミン酸に Nalを添加したときの相乗的な抗ウィル ス(IHNウィルス)効果につ!、て試験した。  In this test example, we tested the synergistic antiviral (IHN virus) effect of adding Nal to catechin, which is a tea catechin!
10 gZmlの茶カテキンないし 1 μ g/mlのフミン酸を含む MEM培地(最小必須 栄養培地)に、更に、 1, 5, 10, 20/zgZmlの Nalを加え、 -ジマス由来の培養細胞 RTG— 2細胞を接種し、更に、一細胞当たり 0. 01個の IHNウィルス(moiO. 01)を 感染させ、 15°C、 pH7. 2で、 10日間培養した。培養後、ウィルス数 (ウィルス力価 T CID /ml)を培養上清を用いて測定した。その結果を表 3に示す。 To a MEM medium containing 10 gZml of tea catechin or 1 μg / ml of humic acid (minimum essential nutrient medium), add 1, 5, 10, 20 / zgZml of Nal. RTG-2 cells were inoculated, and further infected with 0.01 IHN virus (moiO.01) per cell, and cultured at 15 ° C and pH 7.2 for 10 days. After the culture, the number of viruses (virus titer TCID / ml) was measured using the culture supernatant. The results are shown in Table 3.
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[表 3]  [Table 3]
ウィルス力価 ( l o g 1 0 T C I D 5。ノ m l ) Virus titer (log 10 TCID 5 , ml)
Figure imgf000011_0001
次に、サクラマス稚魚への経口投与試験及び毒性試験により、本発明を具体的に 説明する。
Figure imgf000011_0001
Next, the present invention will be specifically described by an oral administration test and a toxicity test on juvenile salmon.
試験例 4 Test example 4
二つの 60リットル水槽に、平均体重 0. 5gのサクラマス稚魚 220尾を収容し、 10°C の飼育水(地下水)を 2リットル Z分の割合で供給しながら、一方の稚魚にフミン酸及 び Nalを混合した餌を、他方の稚魚にはコントロールとしてそれらを混合しない通常 の餌を与えた。小さい粒状の餌 100g当たりフミン酸 5mgと NaI50mgを混合し、フィ ードオイル 5gでコーティングすることによって試薬の水への溶解拡散を防 、だ。 IHN ウィルスを含んだ液(ウィルス液)をマイクロポンプを通してウィルス数(ウィルス力価) 100TCID Zml飼育水になるように調整して、 5日間飼育し、ウィルス感染した。餌  Two 60-liter aquariums contain 220 juvenile salmon trout with an average weight of 0.5 g, and feed humic acid and humic acid to one juvenile while supplying breeding water (groundwater) at 10 ° C at a rate of 2 liters Z. The Nal-mixed diet was fed, while the other fry were fed a normal diet without them as a control. Mixing 5 mg of humic acid and 50 mg of NaI per 100 g of small granular feed and coating with 5 g of feed oil prevents dissolution and diffusion of reagents into water. A solution containing the IHN virus (virus solution) was adjusted through a micropump to a virus count (virus titer) of 100 TCID Zml in breeding water, bred for 5 days, and infected with the virus. Bait
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はウィルス感染 4日前力も与えた。 30日間稚魚の死亡数を記録した。その結果を図 4 に示す。 Helped four days before the virus infection. Fry deaths were recorded for 30 days. Figure 4 shows the results. Shown in
[0029] 試験例 5  Test Example 5
二つの 60リットル水槽に、平均体重 0. 3gのサクラマス稚魚 220尾を収容し、 10°C の飼育水(地下水)を 2リットル Z分の割合で供給しながら、一方の稚魚にフミン酸及 び Nalを混合した餌を、他方の稚魚にはコントロールとしてそれらを混合しない通常 の餌を与えた。小さい粒状の餌 100g当たりフミン酸 5mgと NaI50mgを混合し、フィ ードオイル 5gでコーティングすることによって試薬の水への溶解拡散を防 、だ。 IHN ウィルスを含んだ液(ウィルス液)をマイクロポンプを通してウィルス数(ウィルス力価) 100TCID Zml飼育水になるように調整して、 5日間飼育し、ウィルス感染した。餌  Two 60-liter aquariums hold 220 juvenile salmon trout with an average weight of 0.3 g, and supply humic acid and humic acid to one juvenile while feeding breeding water (groundwater) at 10 ° C at a rate of 2 liters Z. The Nal-mixed diet was fed, while the other fry were fed a normal diet without them as a control. Mixing 5 mg of humic acid and 50 mg of NaI per 100 g of small granular feed and coating with 5 g of feed oil prevents dissolution and diffusion of reagents into water. A solution containing the IHN virus (virus solution) was adjusted through a micropump to a virus count (virus titer) of 100 TCID Zml in breeding water, bred for 5 days, and infected with the virus. Bait
50  50
はウィルス感染 20日前力も与えた。 30日間稚魚の死亡数を記録した。その結果を図 5に示す。  Helped 20 days before the virus infection. Fry deaths were recorded for 30 days. Figure 5 shows the results.
[0030] 試験例 6 [0030] Test example 6
二つの 60リットル水槽に、平均体重 0. 6-0. 9gのサクラマス稚魚 220尾を収容し、 10°Cの飼育水(地下水)を 2リットル Z分の割合で供給しながら、一方の稚魚にフミン 酸及び Nalを混合した餌を、他方の稚魚にはコントロールとしてそれらを混合しな!ヽ 通常の餌を与えた。小さい粒状の餌 100g当たりフミン酸 10mgと NallOmgを混合し 、フィードオイル 5gでコーティングすることによって試薬の水への溶解拡散を防 、だ。 IHNウィルスを含んだ液(ウィルス液)をマイクロポンプを通してウィルス数(ウィルス 力価) 100TCID  Two 60-liter aquariums contain 220 fish salmon fry, averaging 0.6-0.9 g in weight, and feed breeding water (groundwater) at 10 ° C at a rate of 2 liters Z to one fry. Food mixed with humic acid and Nal was not mixed with the other fry as a control! Normal feed was given. A mixture of 10 mg of humic acid and NallOmg per 100 g of small granular feed was coated with 5 g of feed oil to prevent the reagent from dissolving and diffusing into water. A solution containing IHN virus (virus solution) is passed through a micropump and the number of viruses (virus titer) 100TCID
50 Zml飼育水になるように調整して、 5日間飼育し、ウィルス感染し た。餌はウィルス感染 20日前から与えた。 30日間稚魚の死亡数を記録した。その結 果を図 6に示す。  They were adjusted to 50 Zml breeding water, bred for 5 days, and infected with the virus. Food was given 20 days before virus infection. Fry deaths were recorded for 30 days. Figure 6 shows the results.
[0031] 試験例 7 [0031] Test example 7
本試験例では、毒性試験を行った。二つの 60リットル水槽に、平均体重 0. 3gのサ クラマス稚魚 220尾を収容し、 10°Cの飼育水(地下水)を 2リットル Z分の割合で供給 しながら、一方の稚魚にフミン酸及び Nalを混合した餌を、他方の稚魚にはコントロー ルとしてそれらを混合しない通常の餌を与えた。小さい粒状の餌 100g当たりフミン酸 10mgと NallOmgを混合し、フィードオイル 5gでコーティングすることによって試薬の 水への溶解拡散を防いだ。 30日間稚魚の死亡数を記録した。その結果を図 7に示 す。 In this test example, a toxicity test was performed. Two 60-liter aquariums contain 220 fish salmon fry, averaging 0.3 g in weight, and feed breeding water (groundwater) at 10 ° C at a rate of 2 liters Z while humic acid and The Nal-mixed diet was given, while the other fry were given normal diet without control as a control. Mixing 10 mg of humic acid and NallOmg per 100 g of small granular feed and coating with 5 g of feed oil prevented dissolution and diffusion of reagents into water. Fry deaths were recorded for 30 days. Figure 7 shows the results. You.
[0032] 以上の試験結果から、(1)フミン酸と Nalの経口投与はサクラマスに対してウィルス 感染を防止する効果があること、 (2)フミン酸 5mgZlOOg餌及び NaI50mgZlOOg 餌の混合がウィルス抑制効果をより強く発揮し、この量は、魚体重に換算して、フミン 酸 1. 5mgZkg餌、 NaI15mgZkgに相当すること、(3)フミン酸及び Nalには毒性 は無いこと、等が確認された。  [0032] From the above test results, (1) oral administration of humic acid and Nal has the effect of preventing virus infection against salmon, and (2) mixing of humic acid 5mgZlOOg diet and NaI50mgZlOOg diet has virus inhibitory effect. It was confirmed that, in terms of fish body weight, this amount was equivalent to 1.5 mg Zkg of humic acid diet and 15 mg Zkg of NaI, and (3) humic acid and Nal had no toxicity.
[0033] 試験例 8  [0033] Test Example 8
マイクロプレートに-ヮトリ胎児線維芽細胞浮遊液 X 105細胞 Zml)の 30 IX L/ ゥエルを接種して、 Nal及び緑茶カテキン (主成分:ェピガロカテキンガレート)を所定 濃度になるように細胞培養培地で調整 (PH7. 4)して添加し、更に、予めウィルス力 価測定済みのトリインフルエンザウイルス溶液を接種して感染させ、 37°Cで 3— 5日 間培養した。 Inoculate a microplate with 30 IX L / well of-ヮ fetal embryo fibroblast suspension X 10 5 cells Zml), and inoculate Nal and green tea catechin (main component: epigallocatechin gallate) to a prescribed concentration. The cells were added after being adjusted (PH 7.4) with a culture medium, and further inoculated with an avian influenza virus solution whose virus titer had been measured in advance, and cultured at 37 ° C for 3-5 days.
[0034] 培養終了後、アラマ一ブルー染色を施して細胞変性効果 (CPE)を顕微鏡観察し た。 Nal及びカテキンのそれぞれ単独、両者の種々の組み合わせでウィルス抑制効 果を CPEで判定した。その結果を「トリインフルエンザウイルスに対するョードイオン 及びカテキンのウィルス抑制効果」として表 4に示した。  [0034] After completion of the culture, the cells were stained with Alamar Blue, and the cytopathic effect (CPE) was observed under a microscope. Virus suppression effects were determined by CPE for Nal and catechin alone and in various combinations of both. The results are shown in Table 4 as "The virus-suppressing effect of aodeon and catechin on avian influenza virus".
[0035] [表 4]  [Table 4]
Cytopathic effect(CPE ) of host cells Cytopathic effect (CPE) of host cells
Dilution of virus solution  Dilution of virus solution
Iodo - ion and/or catechin 10° 10' 102 103 104 105 106 Iodo-ion and / or catechin 10 ° 10 '10 2 10 3 10 4 10 5 10 6
Na【 1 jt g/ml ++++ ++++ ++++ +-H- ++ - -Na [1 jt g / ml ++++ ++++ ++++ + -H- ++--
Nal 1 0 U g/ml ++++ ++++ ++++ +++ - - -Nal 1 0 U g / ml ++++ ++++ ++++ +++---
Catechin 1 fi g/ml ++++ l i l t ++++ +++ ++ - -Catechin 1 fi g / ml ++++ l i l t ++++ +++ ++--
Catechin 1 0 U g/ml ++++ ++++ +++ -H- + - - -Catechin 10 0 U g / ml ++++ ++++ +++ -H- +---
Nal 1 g/ml + Catechin 1 μ g/ml + ++++ M M -H-+ + - -Nal 1 g / ml + Catechin 1 μg / ml + ++++ M M -H- + +--
Nal 1 0 g/ml + Catechin 1 U g/ml ++++ ++++ ++ + ++ - - -Nal 10 g / ml + Catechin 1 U g / ml ++++ ++++ ++ + ++---
Nal 1 g/ml + Catechin 1 0 U g/ml ++++ ++++ +++ -H- - - -Nal 1 g / ml + Catechin 10 U g / ml ++++ ++++ +++ -H----
Nal 5 g/ml + Catechin l O jU /ml M M 1 ++ ++++ ++ 一 - -Nal 5 g / ml + Catechin l O jU / ml M M 1 ++ ++++ ++ one--
Na【 1 0 g/ml + Catechin 1 0 g/ml M M M i l ++++ + - 一 -Na 【10 g / ml + Catechin 10 g / ml M M M i ++++++--
Virus alone(=positive control) ++++ + 1 1 ++++ +-H- - No virus(=negative control) Virus alone (= positive control) ++++ + 1 1 ++++ + -H--No virus (= negative control)
*CPE ; ++++ > +++ > ++ > + > - 「 ^ Effective on virus  * CPE; ++++> +++> ++> +>-"^ Effective on virus
[0036] 試験例 9 マイクロプレートにニヮトリ胎児線維芽細胞浮遊液 X 105細胞 Zml)の 30 μ LZ ゥエルを接種して、 Nal及び緑茶カテキン (主成分:ェピガロカテキンガレート)を所定 濃度になるように細胞培養培地で調整 (pH7. 4)して添カ卩し、更に、予めウィルス力 価測定済みのトリニューカッスル病ウィルス溶液を接種して感染させ、 37。Cで 3 5 日間培養した。 [0036] Test Example 9 A microplate is inoculated with 30 μL of chicken fetal fibroblast cell suspension X 10 5 cells Zml), and the cell culture medium is adjusted to a prescribed concentration of Nal and green tea catechin (main component: epigallocatechin gallate). 37. Adjusted pH (pH 7.4) and spiked, then inoculated with a solution of Avian Newcastle disease virus whose virus titer had been measured in advance. C. The cells were cultured for 35 days.
[0037] 培養終了後、アラマ一ブルー染色を施して細胞変性効果 (CPE)を顕微鏡観察し た。 Nal及びカテキンのそれぞれ単独、両者の種々の組み合わせでウィルス抑制効 果を CPEで判定した。その結果を「トリニューカッスル病ウィルスに対するョードイオン 及びカテキンのウィルス抑制効果」として表 5に示した。  [0037] After completion of the culture, the cells were stained with Alamar Blue, and the cytopathic effect (CPE) was observed under a microscope. Virus suppression effects were determined by CPE for Nal and catechin alone and in various combinations of both. The results are shown in Table 5 as "The virus-suppressing effect of aodeon and catechin on avian Newcastle disease virus".
[0038] [表 5]  [0038] [Table 5]
Cytopathic effect(CPE ) of host cells Cytopathic effect (CPE) of host cells
Dilution of virus solution  Dilution of virus solution
lodo-ιοη and/ or catechin 10° 101 102 103 104 105 106 lodo-ιοη and / or catechin 10 ° 10 1 10 2 10 3 10 4 10 5 10 6
Nal 1 U g/ml ■H- ■H-H- ++Nal 1 U g / ml ■ H- ■ H-H- ++
Nal \ Q u g/ml +++ Nal \ Q u g / ml +++
Catechin 1 g/ml -H- ++ Catechin 1 g / ml -H-++
Catechin 1 0 g/ml -HH- ++ Catechin 10 g / ml -HH-++
Nal 1 jt g/ml + Catechin 1 U g/ml ■H-+ ■H-+  Nal 1 jt g / ml + Catechin 1 U g / ml ■ H- + ■ H- +
Nal 1 0 i g/ml + Catechin 1 g/ml +++ -H- Nal 10 i g / ml + Catechin 1 g / ml +++ -H-
Nal 1 U g/ml + Catechin 1 0〃 g/ml +++ +++ Nal 1 U g / ml + Catechin 10 0 g / ml +++ +++
Nal 5 jU g/ml + Catechin 1 0 jU g/ml +-H- Nal 5 jU g / ml + Catechin 10 jU g / ml + -H-
Nal 1 0 /ml + Catechin 1 0 g/ml ■H-H- -H-Nal 10 / ml + Catechin 10 g / mlH-H- -H-
Virus alone(=positive control) +H-H- ++Virus alone (= positive control) + H-H- ++
No virus(=negative control) No virus (= negative control)
CPE ; ++++ > +++> ++> >  CPE; ++++> +++> ++>>
Effective on virus  Effective on virus
[0039] 試験例 10 [0039] Test example 10
マイクロプレートにニヮトリ胎児線維芽細胞浮遊液 X 105細胞 Zml)の 30 IX L/ ゥエルを接種して、 Nal及び緑茶カテキン (主成分:ェピガロカテキンガレート)を所定 濃度になるように細胞培養培地で調整 (pH7. 4)して添カ卩し、更に、予めウィルス力 価測定済みのトリニューカッスル病ウィルス溶液を接種して感染させ、 37°Cで 3 5 日間培養した。 Was inoculated 30 IX L / Ueru of Niwatori fetal fibroblast cell suspension X 10 5 cells ZML) microplates, Nal and green tea catechins (ingredient: the E pin gallocatechin gallate) to a predetermined concentration cell culture The mixture was adjusted with a medium (pH 7.4), supplemented with cauliflower, and inoculated with a solution of Avian Newcastle Disease Virus, whose virus titer had been previously measured, for infection, and cultured at 37 ° C for 35 days.
[0040] 培養終了後、アラマ一ブルー染色を施してマイクロプレートの吸光度 (O. D. )をマ イク口プレートリーダーで測定し、ウィルスを接種しない陰性対照を基にして生細胞の 生残率を求めた。その結果を図 8に示した。 After completion of the culture, the cells were stained with Alamar Blue and the absorbance (OD) of the microplate was measured using a microplate reader. The survival rate was determined. The results are shown in FIG.
[0041] 試験例 11 Test Example 11
(1)試験 1  (1) Test 1
マイクロプレートに、ゥシ株化細胞の MDBK細胞浮遊液(1 X 105細胞 Zml)の 30 μ L/ゥエルを接種して、 Nal及び緑茶カテキン (主成分:ェピガロカテキンガレート) を所定濃度になるように細胞培養培地で調整 (PH7. 4)して添加し、更に、予めウイ ルスカ価測定済みのゥシウィルス性下痢症ウィルス溶液を接種して感染させ、 37°C で 3— 5日間培養した。 A microplate is inoculated with 30 μL / well of MDBK cell suspension (1 × 10 5 cells Zml) of Nishi and green tea catechin (main component: epigallocatechin gallate) at a specified concentration. Cell culture medium (pH 7.4), add, and inoculate with a Psivirus diarrhea virus solution whose whisker value has been measured in advance, and incubate for 3-5 days at 37 ° C. did.
[0042] 培養終了後、アラマ一ブルー染色を施して細胞変性効果 (CPE)を顕微鏡観察し た。 Nal及びカテキンのそれぞれ単独、両者の種々の組み合わせでウィルス抑制効 果を CPEで判定した。その結果を「ウィルス感染ほ乳動物細胞に対するョード 'カテ キンのウィルス抑制効果」として表 6の上段に示した。  [0042] After completion of the culture, the cells were stained with Alamar Blue, and the cytopathic effect (CPE) was observed under a microscope. Virus suppression effects were determined by CPE for Nal and catechin alone and in various combinations of both. The results are shown in the upper part of Table 6 as "Effective effect of odo'catechin on virus-infected mammalian cells".
[0043] (2)試験 2  (2) Test 2
マイクロプレートに、ネコ腎線維芽細胞浮遊液(1 X 105細胞/ ml)の 30 L/ゥェ ルを接種して、 Nal及び緑茶カテキン (主成分:ェピガロカテキンガレート)を所定濃 度になるように細胞培養培地で調整 (PH7. 4)して添加し、更に、予めウィルス力価 測定済みのネコ力リシウィルス溶液を接種して感染させ、 37°Cで 3— 5日間培養した A microplate is inoculated with 30 L / well of a feline renal fibroblast suspension (1 × 10 5 cells / ml), and Nal and green tea catechin (main component: epigallocatechin gallate) are in a prescribed concentration. The cells were adjusted with cell culture medium (PH 7.4), added, and inoculated with a feline virulent virus solution whose virus titer had been measured in advance, and cultured at 37 ° C for 3-5 days.
[0044] 培養終了後、アラマ一ブルー染色を施して細胞変性効果 (CPE)を顕微鏡観察し た。 Nal及びカテキンのそれぞれ単独、両者の種々の組み合わせでウィルス抑制効 果を CPEで判定した。その結果を「ウィルス感染ほ乳動物細胞に対するョード 'カテ キンのウィルス抑制効果」として表 6の下段に示した。 [0044] After completion of the culture, the cells were stained with Alamar Blue, and the cytopathic effect (CPE) was observed under a microscope. Virus suppression effects were determined by CPE for Nal and catechin alone and in various combinations of both. The results are shown in the lower part of Table 6 as "Effective effect of eodo'catechin on virus-infected mammalian cells".
[0045] [表 6] ウィルス力価 動物ウイルス Nal濃度 ·力テキン¾度 (logio TCIDso/ml) ゥシウィルス性下痢症ウィルス 1 10 /1^ +カテキン 10 ^¾^1 105 0 [Table 6] Viral titer Animal virus Nal concentration · Viscosity (logio TCIDso / ml) Psivirus diarrhea virus 1 10/1 ^ + catechin 10 ^ ¾ ^ 1 10 5 0
コントロール (Nalなし、 カテキンなし) 106.5 Control (no Nal, without catechin) 10 6.5
ウィルスを数十分の 1 に抑 ¾ Reduce virus to tens of minutes ¾
Cytopathic effect (CPE) Cytopathic effect (CPE)
Dilution of virus solution  Dilution of virus solution
Nal and catechin 105 106 Nal and catechin 10 5 10 6
Nal 10 g/ml + catechin 10 μg/mi +++ ——  Nal 10 g / ml + catechin 10 μg / mi +++ ——
Control {virus alone) +++ - - + ネコ力リシウィルス Nal 10 i/g/ml +カテキン 10 g ml 106 5 Control (virus alone) +++--+ Feline riculovirus Nal 10 i / g / ml + Catechin 10 g ml 10 6 5
コントロール (Nalなし、 カテキンなし) 107-5 Control (no Nal, without catechin) 10 7 - 5
ウィルスを 1 /10に抑 a  Reduce virus by 1/10 a
[0046] 製造例 [0046] Manufacturing example
通常の製パン原料に対し、予め調製したフミン酸を 5mgZl00g原料及び NaI150 mgZlOOg原料力もなる抗ウィルス性組成物を配合して混合し、常法により、食パン 製品を製造し、目的の機能性食品を製造した。  5 mg Zl00 g raw material and NaI 150 mg ZlOOg raw material are blended with ordinary bakery raw material and mixed with an antiviral composition that also has the power of the raw material, and bread products are manufactured in a conventional manner to produce the intended functional food. Manufactured.
産業上の利用可能性  Industrial applicability
[0047] 以上詳述したように、本発明は、抗ウィルス性組成物等に係るものであり、本発明に より、エイズウイルス等のウィルスによる感染症の予防、治療に著効を発揮する新規 抗ウィルス機能を有する機能性食品、抗ウィルス製剤等を製造し、提供することがで きる。ウィルス感染細胞を選択的に不活化する作用を有する新規抗ウィルス薬剤を 提供できる。また、本発明により、例えば、抗 HIVウィルス活性を付加した機能性食 品を提供することができる。本発明の原理であるウィルス感染細胞におけるョードィ オンを使用したョード生成'デリパテイブシステムを利用することにより、各種ウィルス 感染細胞の細胞死の発現機序の解明や新しいウィルス感染症の病理学的評価方法 の確立に資することができる。本発明の抗ウィルス製剤は、低コストで、しかも安全性 が高いことから、当該抗ウィルス製剤を用いることにより、例えば、南アフリカ等におけ るエイズ救済活動に迅速かつ緊急に対応し貢献することができる。 図面の簡単な説明 [0047] As described in detail above, the present invention relates to an antiviral composition and the like, and according to the present invention, a novel antiviral composition which is extremely effective in preventing and treating infectious diseases caused by viruses such as AIDS virus. Functional foods having antiviral functions, antiviral preparations, etc. can be manufactured and provided. It is possible to provide a novel antiviral drug having an action of selectively inactivating virus-infected cells. Further, according to the present invention, for example, a functional food to which an anti-HIV virus activity is added can be provided. Elucidation of the mechanism of cell death in various virus-infected cells and the pathogenesis of new virus infections can be achieved by utilizing the principle of the present invention, which uses the "degeneration system using eodoion in virus-infected cells". It can contribute to the establishment of an evaluation method. Since the antiviral preparation of the present invention is inexpensive and highly safe, it is possible to quickly and urgently respond to and contribute to AIDS relief activities in South Africa and the like by using the antiviral preparation. it can. Brief Description of Drawings
[0048] [図 1]本発明の試験例で用いた電気泳動装置の上面図及び断面図を示す。 [図 2]ウィルス感染 RTG—2細胞の電気泳動図を示す。 FIG. 1 shows a top view and a cross-sectional view of an electrophoresis apparatus used in a test example of the present invention. FIG. 2 shows an electrophoretogram of virus-infected RTG- 2 cells.
[図 3]RTG— 2細胞及び CHSE— 214細胞の電気泳動図を示す。 FIG. 3 shows electropherograms of RTG-2 cells and CHSE-214 cells.
[図 4]試験例 4のサクラマス稚魚への経口投与試験の結果を示す。 FIG. 4 shows the results of an oral administration test to juvenile salmon in Test Example 4.
[図 5]試験例 5のサクラマス稚魚への経口投与試験の結果を示す。 FIG. 5 shows the results of an oral administration test to juvenile salmon trout in Test Example 5.
[図 6]試験例 6のサクラマス稚魚への経口投与試験の結果を示す。 FIG. 6 shows the results of an oral administration test to juvenile salmon trout in Test Example 6.
圆 7]毒性試験の結果を示す。 [7] Shows the results of the toxicity test.
圆 8]試験の手順及びトリ-ユーカツスル病ウィルス感染鶏胎児繊維芽細胞に対する ョードイオン及び茶カテキンの細胞生残効果を示す。 [8] This section shows the test procedure and the cell survival effect of bode ion and tea catechin on chicken fetal fibroblasts infected with avian-Eucasian disease virus.

Claims

請求の範囲 The scope of the claims
[1] ョードイオン又はョードイオンを生成する化合物を有効成分として含むことを特徴と するウィルス感染細胞を選択的に不活性化する作用を有する抗ウィルス性組成物。  [1] An antiviral composition having an action of selectively inactivating virus-infected cells, characterized by containing, as an active ingredient, an iodine ion or a compound that produces an iodine ion.
[2] ョードイオンとポリフエノールイ匕合物を組み合わせた請求項 1に記載の抗ウィルス性 組成物。  [2] The antiviral composition according to claim 1, wherein a combination of an anode and a polyphenol conjugate is used.
[3] 請求項 1又は 2に記載の抗ウィルス性組成物を配合して抗ウィルス機能を付加した ことを特徴とする抗ウィルス機能を有する機能性食品。  [3] A functional food having an antiviral function, wherein the antiviral composition according to claim 1 or 2 is blended to add an antiviral function.
[4] 請求項 1又は 2に記載の抗ウィルス性組成物力 なることを特徴とするウィルス感染 細胞を選択的に不活性化する作用を有する抗ウィルス薬剤。 [4] An antiviral agent having an action of selectively inactivating virus-infected cells, characterized in that the antiviral composition according to claim 1 or 2 is used.
[5] ョードイオン又はョードイオンを生成する化合物をウィルス感染細胞を含む生体細 胞系に供給して、ウィルス感染細胞内に特異的にョード(1Z2I )を生成させ、当該ョ [5] Supplying an anode or a compound generating an anode to a living cell system containing a virus-infected cell to specifically produce an anode (1Z2I) in the virus-infected cell,
2  2
ード(1Z2I )の作用によりウィルス感染細胞を選択的に不活ィ匕させ、死滅させること  To selectively inactivate and kill virus-infected cells by the action of the drug (1Z2I)
2  2
を特徴とするウィルス感染細胞の選択的不活化方法。  A method for selectively inactivating virus-infected cells, characterized in that:
[6] ョードイオン又はョードイオンを生成する化合物をウィルス感染細胞を含む生体細 胞系に供給して、ウィルス感染細胞内に特異的にョード(1Z2I )を生成させることを [6] It is necessary to supply an olive ion or a compound that produces an iodide ion to a living cell system containing a virus-infected cell to specifically produce an eodo (1Z2I) in the virus-infected cell.
2  2
特徴とするウィルス感染細胞における選択的ョード(1Z2I )生成 'デリバティブシス  Characteristic selective generation of (1Z2I) in virus-infected cells' Derivative cis
2  2
テム。  Tem.
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