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WO2014115860A1 - Agent virucide - Google Patents

Agent virucide Download PDF

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Publication number
WO2014115860A1
WO2014115860A1 PCT/JP2014/051590 JP2014051590W WO2014115860A1 WO 2014115860 A1 WO2014115860 A1 WO 2014115860A1 JP 2014051590 W JP2014051590 W JP 2014051590W WO 2014115860 A1 WO2014115860 A1 WO 2014115860A1
Authority
WO
WIPO (PCT)
Prior art keywords
metasilicate
virucidal
aqueous solution
virus
sodium metasilicate
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/JP2014/051590
Other languages
English (en)
Japanese (ja)
Inventor
朋子 田島
吉平 ▲高▼畑
亮 門田
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
TMC CO Ltd
Osaka Metropolitan University
TMC Co
Original Assignee
TMC CO Ltd
Osaka Prefecture University PUC
TMC Co
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by TMC CO Ltd, Osaka Prefecture University PUC, TMC Co filed Critical TMC CO Ltd
Priority to JP2014558639A priority Critical patent/JPWO2014115860A1/ja
Publication of WO2014115860A1 publication Critical patent/WO2014115860A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N59/00—Biocides, pest repellants or attractants, or plant growth regulators containing elements or inorganic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2/00—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor
    • A61L2/16—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor using chemical substances
    • A61L2/18—Liquid substances or solutions comprising solids or dissolved gases

Definitions

  • the present invention relates to a virucidal agent.
  • nosocomial infections in animal hospitals are becoming a problem.
  • One of the causes of nosocomial infections is inadequate disinfection of bacteria and viruses attached to medical devices, breeding cages, and excreta.
  • surfactants that are quaternary ammonium salts such as ethanol, povidone iodine, sodium hypochlorite, glutaraldehyde, benzalkonium chloride, and glycine surfactants are generally used.
  • Various disinfectants are used.
  • Ethanol is effective against most bacteria and some viruses, but it causes deterioration of plastic and rubber products.
  • Popidone iodine can be used for plastic products and rubber products, but its effectiveness is weak and it cannot be used for metal products because it is corrosive.
  • Sodium hypochlorite is effective against most bacteria and viruses and inactivates viruses that are resistant to ethanol, such as parvoviruses and noroviruses, but is corrosive, so it is a metal product such as medical devices and cages. Can not be used.
  • Glutaraldehyde also inactivates viruses resistant to ethanol, such as parvovirus and norovirus, but is difficult to handle because it has the property of denaturing proteins.
  • sodium metasilicate is also called water glass, and its highly concentrated solution has high viscosity.
  • it is used for various purposes because it is highly safe for humans and has little environmental load or corrosivity.
  • it is used as an assistant for soap and detergent, an agglomeration aid for water purification, a peptizer for ceramics (dispersing agent), and an inorganic adhesive, and it contains a glycine surfactant. It is also used in cleaning compositions for appliances, dentures, and orthodontic appliances.
  • Patent Document 1 Japanese Patent Publication No. 2005-514427
  • Patent Document 2 Japanese Patent Publication No. 2005-514427
  • Patent Document 3 Japanese Patent Laid-Open No. 2012-2333058
  • Patent Document 4 Japanese Patent Laid-Open No. 2010-057846
  • compositions contain a component having a virucidal activity as an active ingredient in addition to sodium metasilicate, and sodium metasilicate is only used as a so-called builder such as an alkaline agent in the composition.
  • Patent Document 5 Japanese Patent Publication No. 2012-522011
  • Patent Document 6 Japanese Patent Publication No. 2012-522012 disclose pharmaceutical compositions for respiratory tract infections caused by bacteria such as influenza virus, rhinovirus, and pneumoniae.
  • These pharmaceutical compositions include a sodium salt such as sodium metasilicate and a calcium salt such as calcium citrate, and the ratio of sodium ions to calcium ions is adjusted to a specific range.
  • sodium metasilicate exhibits virucidal activity or bactericidal activity.
  • Non-Patent Document 1 describes that several types of compositions containing sodium metasilicate (including commercially available products) showed effectiveness against rotavirus. However, these compositions are compositions containing a quaternary ammonium salt, and NPL 1 does not suggest anything that sodium metasilicate exhibits a virucidal action.
  • Non-Patent Document 2 describes that a 5% (w / w) sodium metasilicate solution is ineffective against vesicular stomatitis virus.
  • sodium metasilicate is approved by the FDA as a food disinfectant and is effective against Escherichia coli O157, Salmonella and Listeria in meat (Non-Patent Documents 3 to 5)
  • Non-Patent Documents 3 to 5 sodium metasilicate exhibits virucidal activity.
  • sodium metasilicate which is widely used as an alkaline agent, is not only a herpes virus or coronavirus having an envelope, but also a parvo having no envelope. It has been found that viruses and caliciviruses also have a virucidal action, and the present invention has been completed.
  • an object of the present invention is to provide a virucidal agent having a broad virucidal spectrum and easy to handle.
  • the virucidal agent according to the present invention contains a metasilicate such as sodium metasilicate as an active ingredient.
  • the present invention provides a drug that exhibits a virucidal action not only on herpesviruses and coronaviruses having an envelope, but also on parvoviruses and caliciviruses that do not have an envelope, and is easy to handle.
  • the virucidal agent according to the present invention contains water-soluble metasilicate as an active ingredient.
  • the metasilicate is, for example, a sodium salt and may be a potassium salt, but sodium metasilicate is preferred.
  • the object to which the virusicide according to the present invention is applied is not particularly limited as long as it is a place or object in which the presence of a virus is suspected.
  • it may be a dental instrument such as a dental reamer or a denture, a medical instrument such as a scalpel, tweezers or scissors, and may be a cage for various animals including pets.
  • a dental instrument such as a dental reamer or a denture
  • a medical instrument such as a scalpel, tweezers or scissors
  • it is the floors and walls of various facilities such as hospitals, general households, companies, etc., door knobs, window handles, sofas, beds, desks, switches such as lighting switches, It can be a toy.
  • feces and vomits of animals including humans can be objects.
  • perishable foods such as beef, chicken, and vegetables, processed foods, and animals including humans themselves can be objects.
  • metasilicate Since metasilicate is not corrosive, it can be applied to objects in the anti-range including metal products.
  • the virucidal agent according to the present invention acts on viruses present in such objects. Moreover, since the sodium metasilicate should just contact a virus, not only when a virus exists on the surface of a target object, but also when it exists in a target object like feces and a vomit, a virucidal effect is exhibited.
  • the virusicide according to the present invention is mainly used as an aqueous solution of metasilicate.
  • concentration of the aqueous solution of metasilicate varies depending on the object to be used and the contact time, but the minimum concentration of sodium metasilicate is, for example, 0.01 mg / g, 0.05 mg / g, 0 It can be 1 mg / g.
  • the preferred concentration is 0.06 mg / g or more, desirably 0.30 mg / g or more, more desirably 0.6 mg / g or more.
  • the upper limit concentration is not particularly limited, but for example, sodium metasilicate is 200 mg / g, 100 mg / g, 50 mg / g, or 10 mg / g.
  • the virucidal agent according to the present invention is effective by bringing an aqueous solution of sodium metasilicate into contact with the object.
  • the method of contacting is not particularly limited.
  • an object is immersed in an aqueous solution of metasilicate, an aqueous solution of metasilicate is sprayed on the object, an aqueous solution of metasilicate is applied to the object, an aqueous solution of metasilicate
  • the method may include wiping with a wiper that contains metasilicate in the object.
  • sodium metasilicate may be sprinkled on the object.
  • the contact time varies depending on the concentration of metasilicate and the contact temperature, it is preferably at least 1 minute at room temperature, preferably 5 minutes or more, and more preferably 10 minutes or more at a preferred concentration of 1.2 mg / g solution. Yes, for a 0.6 mg / g solution, it is preferably 5 minutes or longer.
  • the contact temperature may be room temperature or a room temperature of about 5 to 35 ° C., and no special heating or cooling is required.
  • the virucidal composition according to the present invention comprises a metasilicate and a base necessary for contacting with an object.
  • a base is, for example, water for making an aqueous solution, a support for making a wiper, and an excipient for making tablets or granules.
  • the support is, for example, a woven fabric and may be a non-woven fabric.
  • a composition formulated with an excipient is dissolved in water to contain a predetermined concentration of metasilicate at the time of use.
  • the virucidal action means that the virus cannot be propagated.
  • a virucidal agent means the compound which has such a virucidal action.
  • the composition according to the present invention may contain other virucidal agents and other bactericides.
  • the virucidal composition according to the present invention is used not only in medical instruments and medical facilities but also in homes, it is preferable to use other virucidal agents and sterilizing agents, particularly in handling.
  • metasilicate has bactericidal effect on bacteria such as Escherichia coli and Salmonella. Therefore, when other fungicides are used in combination, it is preferable to use an alkyl polyaminoethyl glycine salt and / or an alkyl diaminoethyl glycine salt having a moderate effect.
  • the composition for virucidal use according to the present invention contains only the necessary base for bringing the metasilicate into contact with the object and the above-mentioned bactericidal agent added as necessary. It may contain optional ingredients that do not affect the virucidal action, such as agents, fragrances, and chelating agents.
  • the aqueous solution of sodium metasilicate exhibits alkalinity, precipitation occurs in an aqueous solution around pH 7, and the virucidal action is lost, so there is no need for neutralization when used as an aqueous solution. Therefore, the composition according to the present invention does not contain acids such as hydrochloric acid, phosphoric acid and sulfuric acid necessary for neutralization.
  • the virucidal agent or virucidal composition according to the present invention acts on various viruses with or without an envelope.
  • the virus of interest can be, for example, a herpes virus, a coronavirus, a parvovirus, a calicivirus, a feline infectious peritonitis virus, or an influenza virus.
  • Feline parvovirus PLI-IV strain feline calicivirus F9 strain, feline herpesvirus 80-1 strain, feline infectious peritonitis virus 79-1146 strain, Aujeszky's disease virus Yamagata S81 strain were used.
  • Feline parvovirus, feline calicivirus, feline herpes virus and Aujeszky's disease virus were propagated in feline kidney-derived cell line CRFK, and feline infectious peritonitis virus was propagated in fetal fetal cell line fcwf-4.
  • a virus solution containing sterilized distilled water instead of sodium metasilicate was reacted in the same manner. Dilute the treated specimen 10-fold stepwise, inoculate the cells, and for feline calicivirus, feline herpesvirus, feline infectious peritonitis virus, after culturing for 2 days, determine the presence or absence of viral infection by the cytopathic effect of the virus 50% tissue culture infection concentration (TCID 50 / ml) was determined.
  • feline parvovirus After culturing for 4 days, the cells were detached with trypsin and washed with PBS. After re-floating in PBS, it was smeared on a 12-hole highly water-repellent printing slide glass and fixed with acetone. Thereafter, the presence or absence of infection was determined by the indirect fluorescent antibody method using feline serum vaccinated with FPV as the primary serum and FITC-labeled anti-cat IgG goat serum as the secondary serum, and TCID 50 / ml was determined. The results are shown in Table 1.
  • feline parvovirus, feline calicivirus, feline herpes virus, Aujeszky's disease virus is reacted with an equivalent amount of 1.2 mg / g sodium metasilicate aqueous solution at room temperature for 5 minutes, Growth was completely prevented.
  • the feline infectious peritonitis virus was less effective than the above four types of viruses, but the infection concentration was reduced to 1 / 10,000.
  • feline calicivirus When feline calicivirus was treated with 0.6 mg / g sodium metasilicate aqueous solution for 1 minute, the infection concentration decreased to 1 / 10,000 or less, and the growth was completely prevented by treatment for 5 minutes. In addition, no effect was observed at 0.12 mg / g. On the other hand, feline herpesvirus was not effective at both 0.6 mg / g and 0.12 mg / g. In addition, cytotoxicity to CRFK cells was observed in an aqueous solution having a concentration of 15 mg / g, and the action on these viruses could not be observed. However, the antiviral action of the aqueous sodium metasilicate solution was not lost even at the concentration.
  • Pulux (trade name: containing 6 w / v% sodium hypochlorite), which is widely used as a disinfectant, was diluted to contain 1% sodium hypochlorite. The added solution was reacted in the same manner. After 10-fold serial dilution, CRFK cells were inoculated and cultured for 2 days, and then the presence or absence of virus infection was determined by cytopathic effect, and TCID 50 / ml was determined. The results are shown in Table 3.
  • the feline calicivirus was completely inhibited from growing with a 1.2 mg / g sodium metasilicate aqueous solution even in a state in which fetal calf serum was mixed up to 20%.
  • Pulux diluted to contain 1% sodium hypochlorite inhibited the virucidal action only by adding fetal calf serum to a concentration of 1%.
  • Example 2 As shown in Table 4, the approximately 2-fold diluted solution (4.5 mg / g sodium metasilicate aqueous solution) of Example 2 showed a virucidal action upon contact for 1 minute. When the bactericidal agent was used in combination, the virucidal effect of sodium metasilicate tended to decrease, but even when the bactericidal agent was used in combination, the virucidal effect of sodium metasilicate was not lost.
  • the feline parvovirus added to the stool was completely prevented from growing by contact with a 6.0 mg / g sodium metasilicate aqueous solution for 5 minutes. A similar inhibition was seen with 1% Pulux.
  • the virus solution was prepared by reacting 1 ml of the virus solution with 5 ml of a 1.2 mg / g sodium metasilicate aqueous solution.
  • the results are shown in Table 7.
  • the virus adhering to the towel was completely prevented from growing by being immersed in an aqueous sodium metasilicate solution for 30 minutes.
  • Influenza A virus A / panama / 2007/99 (H3N2) used as a vaccine was used.
  • the reaction was carried out with an equivalent amount of 1.2 mg / g sodium metasilicate aqueous solution for 5 minutes at room temperature.
  • MDCK cells were inoculated, cultured for 4 days, and the presence or absence of virus infection was determined by cytopathic effect, and TCID 50 / ml was determined.
  • TCID 50 / ml was determined as a control.
  • a virus solution and an equivalent amount of sterile distilled water were reacted. The results are shown in Table 8.
  • the influenza virus was also prevented from growing.
  • the feline parvovirus used above is a virus belonging to the genus Parvoviridae, and does not have an envelope.
  • Feline calicivirus is a virus belonging to the genus Besivirus of the Caliciviridae family and does not have an envelope.
  • Feline herpesvirus (feline viral rhinotracheitis virus) and Aujeszky's disease virus are viruses belonging to the genus Baricellovirus of the herpesviridae family and have an envelope.
  • the feline infectious peritonitis virus is a virus belonging to the genus Alphacoronavirus of the Coronaviridae family and has an envelope.
  • viruses belonging to the same family and the same genus have similar physicochemical properties, they are considered to have the same susceptibility to virucidal agents. Therefore, canine parvoviruses belonging to the genus Parvoviridae, porcine parvoviruses, B19 viruses belonging to the genus Parvoviridae erythrovirus (infecting humans), noroviruses belonging to the genus Besiviridae (infecting humans), herpes
  • sodium metasilicate is also effective for varicella / zoster virus (infecting humans) belonging to the genus Baricellovirus genus, and for porcine infectious gastroenteritis virus belonging to the coronavirus family Alpha coronavirus genus.
  • sodium metasilicate has a virucidal action on various viruses such as influenza virus regardless of the presence or absence of an envelope.
  • a virucidal agent having a broad virucidal spectrum and easy to handle is provided.

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  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Agronomy & Crop Science (AREA)
  • Inorganic Chemistry (AREA)
  • Pest Control & Pesticides (AREA)
  • Plant Pathology (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Dentistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Environmental Sciences (AREA)
  • Agricultural Chemicals And Associated Chemicals (AREA)

Abstract

Le problème selon l'invention est de fournir un agent virucide facile à manipuler avec un large spectre virucide. La solution de l'invention concerne un agent virucide avec comme principe actif un métasilicate soluble dans l'eau tel que du métasilicate de sodium. Plus spécifiquement, grâce à une méthode telle que la trempe, l'essuyage ou la pulvérisation, une solution aqueuse de métasilicate de sodium avec une teneur d'au moins 0,01 mg/g, de préférence 0,06 mg/g, est mise en contact avec un sujet tel qu'un instrument médical, une cage d'élevage, ou des déjections animales à une température normale pendant au moins une minute, de préférence environ 10 minutes.
PCT/JP2014/051590 2013-01-25 2014-01-25 Agent virucide Ceased WO2014115860A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP2014558639A JPWO2014115860A1 (ja) 2013-01-25 2014-01-25 殺ウイルス剤

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JP2013012398 2013-01-25
JP2013-012398 2013-01-25

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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2019107510A1 (fr) * 2017-11-29 2019-06-06 株式会社フリーキラ製薬 Agent antimicrobien contenant de l'acide hypochloreux
JP2020039263A (ja) * 2018-09-07 2020-03-19 Ｋｔｅｎ Ｂｉｏ株式会社 ウイルス消毒効果判定方法及び該判定方法により選定された抗ウイルス消毒剤
WO2020137157A1 (fr) * 2018-12-27 2020-07-02 東亞合成株式会社 Agent antivirus non enveloppé et composition le contenant, et produit antiviral et son procédé de production
JPWO2022239605A1 (fr) * 2021-05-11 2022-11-17

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS6425724A (en) * 1987-03-31 1989-01-27 Ueno Seiyaku Oyo Kenkyujo Kk Suppressant against retrovirus
JPH06271472A (ja) * 1992-10-14 1994-09-27 Matsushita Electric Ind Co Ltd 抗ウィルス性組成物およびその製造方法
WO2004032626A2 (fr) * 2002-10-10 2004-04-22 Sequoia Pacific Research Company, L.L.C. Procede de traitement d'un environnement pouvant etre ou etant contamine par une bacterie, un virus et/ou de spore indesirables
WO2010047108A1 (fr) * 2008-10-24 2010-04-29 メルシャン株式会社 Procédé d'inactivation de calicivirus

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS6425724A (en) * 1987-03-31 1989-01-27 Ueno Seiyaku Oyo Kenkyujo Kk Suppressant against retrovirus
JPH06271472A (ja) * 1992-10-14 1994-09-27 Matsushita Electric Ind Co Ltd 抗ウィルス性組成物およびその製造方法
WO2004032626A2 (fr) * 2002-10-10 2004-04-22 Sequoia Pacific Research Company, L.L.C. Procede de traitement d'un environnement pouvant etre ou etant contamine par une bacterie, un virus et/ou de spore indesirables
WO2010047108A1 (fr) * 2008-10-24 2010-04-29 メルシャン株式会社 Procédé d'inactivation de calicivirus

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
JOURNAL OF FOOD PROTECTION, vol. 67, no. 7, 2004, pages 1501 - 1506 *
VETERINARY RECORD, vol. 93, no. 24, 1973, pages 620 - 624 *

Cited By (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2019107510A1 (fr) * 2017-11-29 2019-06-06 株式会社フリーキラ製薬 Agent antimicrobien contenant de l'acide hypochloreux
US12133929B2 (en) 2017-11-29 2024-11-05 Freekira Pharmaceutical Inc. Antimicrobial agent containing hypochlorous acid
JP2020039263A (ja) * 2018-09-07 2020-03-19 Ｋｔｅｎ Ｂｉｏ株式会社 ウイルス消毒効果判定方法及び該判定方法により選定された抗ウイルス消毒剤
JP7338134B2 (ja) 2018-09-07 2023-09-05 Ｋｔｅｎ Ｂｉｏ株式会社 ウイルス消毒効果判定方法及び該判定方法により選定された抗ウイルス消毒剤
EP3903585A4 (fr) * 2018-12-27 2022-09-14 Toagosei Co., Ltd. Agent antivirus non enveloppé et composition le contenant, et produit antiviral et son procédé de production
JPWO2020137157A1 (ja) * 2018-12-27 2021-11-11 東亞合成株式会社 非エンベロープ型抗ウイルス剤及びそれを含む組成物並びに抗ウイルス製品及びその製造方法
KR20210108945A (ko) * 2018-12-27 2021-09-03 도아고세이가부시키가이샤 비엔벨로프형 항바이러스제 및 그것을 포함하는 조성물 그리고 항바이러스 제품 및 그의 제조 방법
JP7264178B2 (ja) 2018-12-27 2023-04-25 東亞合成株式会社 非エンベロープ型抗ウイルス剤及びそれを含む組成物並びに抗ウイルス製品及びその製造方法
TWI812814B (zh) * 2018-12-27 2023-08-21 日商東亞合成股份有限公司 抗非套膜型病毒劑及含其之組成物，以及抗病毒製品及其製造方法
CN112638158A (zh) * 2018-12-27 2021-04-09 东亚合成株式会社 抗无包膜病毒型的抗病毒剂和含有其的组合物以及抗病毒制品及其制造方法
WO2020137157A1 (fr) * 2018-12-27 2020-07-02 東亞合成株式会社 Agent antivirus non enveloppé et composition le contenant, et produit antiviral et son procédé de production
KR102757717B1 (ko) * 2018-12-27 2025-01-21 도아고세이가부시키가이샤 비엔벨로프형 항바이러스제 및 그것을 포함하는 조성물 그리고 항바이러스 제품 및 그의 제조 방법
JPWO2022239605A1 (fr) * 2021-05-11 2022-11-17
WO2022239605A1 (fr) * 2021-05-11 2022-11-17 グラフトン株式会社 Agent virucide

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