JPWO2014115860A1 - Viricide - Google Patents
Viricide Download PDFInfo
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- JPWO2014115860A1 JPWO2014115860A1 JP2014558639A JP2014558639A JPWO2014115860A1 JP WO2014115860 A1 JPWO2014115860 A1 JP WO2014115860A1 JP 2014558639 A JP2014558639 A JP 2014558639A JP 2014558639 A JP2014558639 A JP 2014558639A JP WO2014115860 A1 JPWO2014115860 A1 JP WO2014115860A1
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- Prior art keywords
- metasilicate
- virucidal
- aqueous solution
- sodium metasilicate
- virus
- Prior art date
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- NTHWMYGWWRZVTN-UHFFFAOYSA-N sodium silicate Chemical compound [Na+].[Na+].[O-][Si]([O-])=O NTHWMYGWWRZVTN-UHFFFAOYSA-N 0.000 claims abstract description 54
- 239000004115 Sodium Silicate Substances 0.000 claims abstract description 53
- 235000019795 sodium metasilicate Nutrition 0.000 claims abstract description 53
- 229910052911 sodium silicate Inorganic materials 0.000 claims abstract description 53
- 230000003253 viricidal effect Effects 0.000 claims abstract description 44
- 239000007864 aqueous solution Substances 0.000 claims abstract description 35
- 239000003443 antiviral agent Substances 0.000 claims abstract description 21
- 239000004480 active ingredient Substances 0.000 claims abstract description 7
- 238000005507 spraying Methods 0.000 claims abstract 3
- 238000007598 dipping method Methods 0.000 claims abstract 2
- 241000700605 Viruses Species 0.000 claims description 42
- 239000000203 mixture Substances 0.000 claims description 20
- 238000000034 method Methods 0.000 claims description 10
- -1 alkyl diaminoethyl glycine salt Chemical class 0.000 claims description 5
- 230000000844 anti-bacterial effect Effects 0.000 claims description 5
- 125000000217 alkyl group Chemical group 0.000 claims description 3
- 150000001875 compounds Chemical class 0.000 claims description 3
- 125000003630 glycyl group Chemical class [H]N([H])C([H])([H])C(*)=O 0.000 claims 2
- 239000011248 coating agent Substances 0.000 claims 1
- 238000000576 coating method Methods 0.000 claims 1
- 241001465754 Metazoa Species 0.000 abstract description 7
- 210000003608 fece Anatomy 0.000 abstract description 6
- 238000001228 spectrum Methods 0.000 abstract description 3
- 238000009395 breeding Methods 0.000 abstract description 2
- 230000001488 breeding effect Effects 0.000 abstract description 2
- 239000000243 solution Substances 0.000 description 22
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 13
- 241000714201 Feline calicivirus Species 0.000 description 10
- 241000701087 Felid alphaherpesvirus 1 Species 0.000 description 9
- 241000701925 Feline parvovirus Species 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- 241000711475 Feline infectious peritonitis virus Species 0.000 description 7
- 239000005708 Sodium hypochlorite Substances 0.000 description 7
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 description 7
- 241000894006 Bacteria Species 0.000 description 6
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 6
- 239000003899 bactericide agent Substances 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 230000009385 viral infection Effects 0.000 description 6
- 241000711573 Coronaviridae Species 0.000 description 5
- 241000125945 Protoparvovirus Species 0.000 description 5
- 230000000120 cytopathologic effect Effects 0.000 description 5
- 208000015181 infectious disease Diseases 0.000 description 5
- 238000013207 serial dilution Methods 0.000 description 5
- 241000712461 unidentified influenza virus Species 0.000 description 5
- 241001263478 Norovirus Species 0.000 description 4
- 241000701093 Suid alphaherpesvirus 1 Species 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 239000012153 distilled water Substances 0.000 description 4
- 108090000623 proteins and genes Proteins 0.000 description 4
- 102000004169 proteins and genes Human genes 0.000 description 4
- 210000002966 serum Anatomy 0.000 description 4
- 239000004094 surface-active agent Substances 0.000 description 4
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 3
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 3
- 239000004471 Glycine Substances 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- 208000036142 Viral infection Diseases 0.000 description 3
- 238000012258 culturing Methods 0.000 description 3
- 239000000645 desinfectant Substances 0.000 description 3
- 239000012894 fetal calf serum Substances 0.000 description 3
- 230000001605 fetal effect Effects 0.000 description 3
- 235000013305 food Nutrition 0.000 description 3
- 229910052751 metal Inorganic materials 0.000 description 3
- 239000002184 metal Substances 0.000 description 3
- 230000000644 propagated effect Effects 0.000 description 3
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 3
- 241001529453 unidentified herpesvirus Species 0.000 description 3
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- 241000004176 Alphacoronavirus Species 0.000 description 2
- 241000282472 Canis lupus familiaris Species 0.000 description 2
- 206010011409 Cross infection Diseases 0.000 description 2
- 241000282324 Felis Species 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 241000701945 Parvoviridae Species 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 241000607142 Salmonella Species 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 239000004744 fabric Substances 0.000 description 2
- 239000000417 fungicide Substances 0.000 description 2
- WQYVRQLZKVEZGA-UHFFFAOYSA-N hypochlorite Chemical compound Cl[O-] WQYVRQLZKVEZGA-UHFFFAOYSA-N 0.000 description 2
- 239000011630 iodine Substances 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- 238000006386 neutralization reaction Methods 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 229920003023 plastic Polymers 0.000 description 2
- 239000004033 plastic Substances 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 159000000000 sodium salts Chemical class 0.000 description 2
- 238000004659 sterilization and disinfection Methods 0.000 description 2
- 210000004916 vomit Anatomy 0.000 description 2
- 230000008673 vomiting Effects 0.000 description 2
- CPKVUHPKYQGHMW-UHFFFAOYSA-N 1-ethenylpyrrolidin-2-one;molecular iodine Chemical compound II.C=CN1CCCC1=O CPKVUHPKYQGHMW-UHFFFAOYSA-N 0.000 description 1
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 1
- 241000714198 Caliciviridae Species 0.000 description 1
- 241000701931 Canine parvovirus Species 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 241000709661 Enterovirus Species 0.000 description 1
- 241000121268 Erythroparvovirus Species 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 241001333951 Escherichia coli O157 Species 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 241000287828 Gallus gallus Species 0.000 description 1
- 208000005577 Gastroenteritis Diseases 0.000 description 1
- 208000007514 Herpes zoster Diseases 0.000 description 1
- 241000700586 Herpesviridae Species 0.000 description 1
- XQFRJNBWHJMXHO-RRKCRQDMSA-N IDUR Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 XQFRJNBWHJMXHO-RRKCRQDMSA-N 0.000 description 1
- 241000712431 Influenza A virus Species 0.000 description 1
- 241000186781 Listeria Species 0.000 description 1
- 241000845082 Panama Species 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 241000702619 Porcine parvovirus Species 0.000 description 1
- 229920000153 Povidone-iodine Polymers 0.000 description 1
- 206010057190 Respiratory tract infections Diseases 0.000 description 1
- 241000702670 Rotavirus Species 0.000 description 1
- 102000004142 Trypsin Human genes 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- 241000711975 Vesicular stomatitis virus Species 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 238000005054 agglomeration Methods 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000005215 alkyl ethers Chemical class 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 235000015278 beef Nutrition 0.000 description 1
- 229960000686 benzalkonium chloride Drugs 0.000 description 1
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
- FNAQSUUGMSOBHW-UHFFFAOYSA-H calcium citrate Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O.[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O FNAQSUUGMSOBHW-UHFFFAOYSA-H 0.000 description 1
- 239000001354 calcium citrate Substances 0.000 description 1
- 229910001424 calcium ion Inorganic materials 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 239000000919 ceramic Substances 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 235000013330 chicken meat Nutrition 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 239000003599 detergent Substances 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000000531 effect on virus Effects 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 230000000855 fungicidal effect Effects 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 150000002333 glycines Chemical class 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 235000013372 meat Nutrition 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000004745 nonwoven fabric Substances 0.000 description 1
- NRNCYVBFPDDJNE-UHFFFAOYSA-N pemoline Chemical compound O1C(N)=NC(=O)C1C1=CC=CC=C1 NRNCYVBFPDDJNE-UHFFFAOYSA-N 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 235000019353 potassium silicate Nutrition 0.000 description 1
- 229960001621 povidone-iodine Drugs 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 235000021067 refined food Nutrition 0.000 description 1
- 239000005871 repellent Substances 0.000 description 1
- 208000020029 respiratory tract infectious disease Diseases 0.000 description 1
- 239000000344 soap Substances 0.000 description 1
- 229910001415 sodium ion Inorganic materials 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 239000003206 sterilizing agent Substances 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 235000013337 tricalcium citrate Nutrition 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 229960005486 vaccine Drugs 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 239000002759 woven fabric Substances 0.000 description 1
Classifications
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- 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
Landscapes
- 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
【課題】 広範囲な殺ウイルススペクトルを有し、かつ取り扱いの容易な殺ウイルス剤を提供する。【解決手段】 メタケイ酸ナトリウムなどの水溶性のメタケイ酸塩を有効成分とする殺ウイルス剤とする。具体的には、浸漬、拭き取り、噴霧などの方法により、０.０１mg/g以上、好ましくは０.０６mg/g以上のメタケイ酸ナトリウム水溶液と、医療器具や飼育ケージ、動物の糞などの対象物を常温で、１分間以上、好ましくは１０分間程度接触させる。【選択図】なしPROBLEM TO BE SOLVED: To provide a virucidal agent having a broad virucidal spectrum and easy to handle. A virucidal agent comprising a water-soluble metasilicate such as sodium metasilicate as an active ingredient is provided. Specifically, sodium metasilicate aqueous solution of 0.01 mg / g or more, preferably 0.06 mg / g or more, and objects such as medical instruments, breeding cages, animal feces, etc., by dipping, wiping, or spraying. Is contacted at room temperature for 1 minute or longer, preferably about 10 minutes. [Selection figure] None
Description
本発明は、殺ウイルス剤に関する。 The present invention relates to a virucidal agent.
イヌやネコは代表的な伴侶動物である。伴侶動物の増加に伴い、動物病院における院内感染が問題となりつつある。院内感染の原因の一つとして、医療器具や飼育ケージ、排泄物などに付着した細菌やウイルスの不十分な消毒がある。細菌の殺菌やウイルスの不活化には、一般にはエタノールやポビドンヨード、次亜塩素酸ナトリウム、グルタルアルデヒド、塩化ベンザルコニウムなどの４級アンモニウム塩である界面活性剤、グリシン系の界面活性剤などの各種消毒剤が使用される。 Dogs and cats are typical companion animals. With the increase of companion animals, 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. For sterilization of bacteria and virus inactivation, 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.
しかしながら、４級アンモニウム塩はウイルスに対してほとんど効果を示さず、グリシン系の界面活性剤が殺ウイルス作用を示したとの報告はない。エタノールはほとんどの細菌や一部のウイルスに効力を示すが、プラスチック製品やゴム製品の劣化を引き起こす。ポピドンヨードはプラスチック製品、ゴム製品にも使用できるが、その効力が弱く、また、腐食性があるので金属製品には使用できない。次亜塩素酸ナトリウムは、ほとんどの細菌やウイルスには効力を示し、パルボウイルスやノロウイルスなどエタノールには抵抗性を示すウイルスを不活化するが、腐食性を有するので医療器具やケージなどの金属製品には使用できない。また、グルタルアルデヒドはパルボウイルスやノロウイルスなどエタノールに抵抗性を示すウイルスも不活化するが、タンパク質を変性させる性質を有するのでその取扱が容易ではない。 However, quaternary ammonium salts have little effect on viruses, and there is no report that glycine surfactants have demonstrated virucidal action. 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.
このように、現時点では、取扱が容易で、かつ、エンベロープをターゲットとするエタノールなどが効力を示さないパルボウイルスやノロウイルスに対しても効果を示す殺ウイルス剤が存在せず、このような殺ウイルス剤が求められている。 Thus, at present, there is no virucidal agent that is easy to handle and effective against parvoviruses and noroviruses that are not effective for ethanol targeting the envelope. There is a need for agents.
ところで、メタケイ酸ナトリウムは水ガラスとも呼ばれ、その高濃度溶液の粘性は高い。また、ヒトに対する安全性は高く、環境への負荷や腐食性もほとんどないなどの理由から、種々の用途に用いられている。例えば、石けんや洗剤の助剤、浄水用の凝集補助剤、陶業用の解謬剤（分散剤）、無機系の接着剤として用いられており、前記グリシン系の界面活性剤を配合した歯科用の器具、義歯、矯正装置用の洗浄用組成物にも使用されている。 By the way, sodium metasilicate is also called water glass, and its highly concentrated solution has a high viscosity. In addition, it is used for various purposes because it is highly safe for humans and has little environmental load or corrosivity. For example, 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.
また、メタケイ酸ナトリウムを含む殺ウイルス組成物が、例えば、特許文献１（特表２００５−５１４４２７号公報）、特許文献２（特表２００５−５１４４２７号公報）、特許文献３（特開２０１２−２３３０５８号公報）、特許文献４（特開２０１０−０５７８４６号公報）に開示されている。 Moreover, the virusicidal composition containing sodium metasilicate is disclosed in, for example, Patent Document 1 (Japanese Patent Publication No. 2005-514427), Patent Document 2 (Japanese Patent Publication No. 2005-514427), and Patent Document 3 (Japanese Patent Laid-Open No. 2012-2333058). No.) and Patent Document 4 (Japanese Patent Laid-Open No. 2010-057846).
しかしながら、これらの組成物はメタケイ酸ナトリウムの他に有効成分として殺ウイルス活性を有する成分を含み、当該組成物においてメタケイ酸ナトリウムはアルカリ剤などのいわゆるビルダーとして使用されているに過ぎない。 However, these compositions contain a component having a virucidal activity as an active ingredient in addition to sodium metasilicate, and sodium metasilicate is merely used as a so-called builder such as an alkaline agent in the composition.
特許文献５（特表２０１２−５２２０１１号公報）や特許文献６（特表２０１２−５２２０１２号公報）にはインフルエンザウイルスやライノウイルス、肺炎菌などの細菌による気道感染症のための医薬組成物が開示されている。これらの医薬組成物は、メタケイ酸ナトリウムなどのナトリウム塩とクエン酸カルシウムなどのカルシウム塩を含み、ナトリウムイオンとカルシウムイオンの比が特定の範囲に調製された組成物である。しかしながら、メタケイ酸ナトリウムが殺ウイルス活性や殺菌性を示すことについて何も示唆していない。 Patent Document 5 (Special Table 2012-522011) and Patent Document 6 (Special Table 2012-522012) disclose pharmaceutical compositions for respiratory tract infections caused by bacteria such as influenza virus, rhinovirus, and pneumoniae. Has been. 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. However, there is no suggestion that sodium metasilicate exhibits virucidal activity or bactericidal activity.
非特許文献１には、メタケイ酸ナトリウムを含む数種類の組成物（市販品を含む）がロタウイルスに対して有効性を示したことが記載されている。しかしながら、これらの組成物は４級アンモニウム塩を含む組成物であり、非特許文献１もメタケイ酸ナトリウムが殺ウイルス作用を示すことについて何も示唆していない。また、非特許文献２には、５％（w/w）のメタケイ酸ナトリウム溶液は水胞性口炎ウイルスには無効であることが記載されている。 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.
その他にメタケイ酸ナトリウムはＦＤＡが食品用の殺菌剤として認可しており、食肉中の大腸菌Ｏ１５７やサルモネラ属菌、リステリア属菌に対して有効であることを示す報告（非特許文献３〜５）もあるが、これまでのところ、メタケイ酸ナトリウムが殺ウイルス活性を示すという報告は未だ知られていない。 In addition, sodium metasilicate has been 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) However, so far, there has been no report yet that sodium metasilicate exhibits virucidal activity.
本発明者らは、上記の背景技術に鑑みて、鋭意研究に努めたところ、アルカリ剤として汎用されているメタケイ酸ナトリウムが、エンベロープを持つヘルペスウイルスやコロナウイルスだけでなく、エンベロープを持たないパルボウイルスやカリシウイルスにも殺ウイルス作用を有することを見いだし、本願発明を完成するに至った。 In light of the above-mentioned background art, the inventors of the present invention have made extensive studies and found that 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.
すなわち、本発明は、広範囲な殺ウイルススペクトルを有し、かつ取り扱いの容易な殺ウイルス剤を提供することを目的とする。 That is, an object of the present invention is to provide a virucidal agent having a broad virucidal spectrum and easy to handle.
本発明に係る殺ウイルス剤は、メタケイ酸ナトリウムなどのメタケイ酸塩を有効成分とする。 The virucidal agent according to the present invention contains a metasilicate such as sodium metasilicate as an active ingredient.
本発明は、エンベロープを持つヘルペスウイルスやコロナウイルスだけでなく、エンベロープを持たないパルボウイルスやカリシウイルスにも殺ウイルス作用を示し、かつ取り扱いが容易な薬剤を提供する。 The present invention provides a drug that exhibits virucidal action and is easy to handle not only on herpesviruses and coronaviruses having envelopes but also on parvoviruses and caliciviruses not having envelopes.
本発明に係る殺ウイルス剤は水溶性のメタケイ酸塩を有効成分とする。メタケイ酸塩は、例えば、ナトリウム塩であり、カリウム塩であり得るが、メタケイ酸ナトリウムが好ましい。 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.
本発明に係る殺ウイルス剤が適用される対象物は、ウイルスの存在が疑われる場所や物であれば特に制約は受けない。例えば、歯科用リーマや義歯などの歯科向けの器械器具であり、メスやピンセット、ハサミなどの医療向けの器械器具であり、ペットを含めた各種動物用の飼育用ケージであり得る。また、病院や一般家庭、会社等の各種施設の床や壁であり、ドアノブであり、窓の取っ手であり、ソファであり、ベッドであり、机であり、照明用スイッチなどのスイッチ類であり、玩具などでもあり得る。また、ヒトを含む動物の糞便や嘔吐物も対象物となり得る。さらに、牛肉や鶏肉、野菜などの生鮮食料品や加工食品、ヒトを含む動物自身も対象物となり得る。メタケイ酸塩は腐食性がないので、金属製品を含む抗範囲な対象物に適用できる。本発明に係る殺ウイルス剤はこのような対象物に存在するウイルスに作用を及ぼす。また、メタケイ酸ナトリウムがウイルスに接触すればよいので、ウイルスが対象物の表面に存在する場合に限らず、糞便や嘔吐物のように対象物に内在する場合でも殺ウイルス効果は発揮される。 The object to which the virucidal agent 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. For example, 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. Also, 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. In addition, feces and vomits of animals including humans can be objects. Furthermore, perishable foods such as beef, chicken, and vegetables, processed foods, and animals including humans themselves can be objects. 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.
本発明に係る殺ウイルス剤は主としてメタケイ酸塩の水溶液として使用される。メタケイ酸塩の水溶液の濃度は、使用する対象物や接触時間によっても異なるが、その最低濃度は、メタケイ酸ナトリウムとして、例えば、０.０１mg/gであり、０.０５mg/gであり、０.１mg/gであり得る。好ましい濃度は０.０６mg/g以上、望ましくは０.３０mg/g以上、さらに望ましくは０.６mg/ｇ以上である。また、その上限濃度は特に制約がないが、例えば、メタケイ酸ナトリウムとして２００mg/gであり、１００mg/gであり、５０mg/gであり、１０mg/ｇであり得る。 The virucidal agent according to the present invention is mainly used as an aqueous solution of metasilicate. The 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. Moreover, 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.
本発明に係る殺ウイルス剤はメタケイ酸ナトリウムの水溶液を対象物と接触させることにより効果を発揮する。接触させる方法は特に問われず、例えば、メタケイ酸塩の水溶液に対象物を漬ける、メタケイ酸塩の水溶液を対象物に噴霧する、メタケイ酸塩の水溶液を対象物に塗布する、メタケイ酸塩の水溶液を含むワイパーで拭く、メタケイ酸塩を対象物に含ませる方法であり得る。もちろん、メタケイ酸ナトリウムを対象物に振りかけてもよい。 The virucidal agent according to the present invention exhibits its effect by bringing an aqueous solution of sodium metasilicate into contact with an object. The method of contacting is not particularly limited. For example, 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. Of course, sodium metasilicate may be sprinkled on the object.
接触時間は、メタケイ酸塩の濃度、接触温度によっても異なるが、好ましい濃度である１.２mg/gの溶液で室温下で少なくとも１分以上、好ましくは５分以上、さらに望ましくは１０分以上であり、０.６mg/gの溶液では好ましくは５分以上である。また、接触温度は、室温又は５〜３５℃程度の常温でよく、特段の加温や冷却は必要としない。 Although 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.
本発明に係る殺ウイルス用組成物はメタケイ酸塩と、対象物と接触させるために必要な基剤を含む。係る基剤は、例えば、水溶液にするための水であり、ワイパーにするための支持体であり、錠剤や顆粒剤などにするための賦形剤であり得る。支持体は、例えば、織布であり、不織布であり得る。賦形剤を用いて製剤化された組成物は、用時、所定濃度のメタケイ酸塩を含むように水に溶解される。 The composition for virucidal use according to the present invention comprises a metasilicate and a base necessary for contacting with an object. Such 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.
メタケイ酸塩は単独で殺ウイルス作用を示し、本発明に係る殺ウイルス用組成物は他の殺ウイルス剤や殺菌剤を必要とはしない。本発明において、殺ウイルス作用とはウイルスを増殖できない状態にすることを意味する。また、殺ウイルス剤とはかかる殺ウイルス作用を有する化合物を意味する。もっとも、本発明に係る組成物は他の殺ウイルス剤や他の殺菌剤を含み得る。しかしながら、本発明に係る殺ウイルス用組成物は、医療用器具器械や医療施設のみならず、家庭においても使用されるものであるから、好ましくは、他の殺ウイルス剤や殺菌剤、特に取り扱いが困難であるグルタルアルデヒド、腐食性のあるヨード剤や次亜塩素酸塩を含まない。また、本発明に係る組成物はエタノールやイソプロピルアルコールなどの殺菌性アルコールを含むとメタケイ酸塩の沈殿を生じるおそれがあるので、好ましくは係るアルコールを含まない。一方で、メタケイ酸塩は大腸菌やサルモネラ属菌などの細菌についても殺菌効力を有する。従って、他の殺菌剤を併用する場合には、効力の緩和なアルキルポリアミノエチルグリシン塩及び／又はアルキルジアミノエチルグリシン塩を用いるのが好ましい。 Metasilicates exhibit virucidal action alone, and the virucidal composition according to the present invention does not require other virucidal or bactericidal agents. In the present invention, the virucidal action means that the virus cannot be propagated. Moreover, a virucidal agent means the compound which has such a virucidal action. However, the composition according to the present invention may contain other virucidal agents and other bactericides. However, since 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. Contains no difficult glutaraldehyde, corrosive iodine and hypochlorite. Moreover, since the composition which concerns on this invention may produce precipitation of metasilicate when it contains bactericidal alcohols, such as ethanol and isopropyl alcohol, Preferably it does not contain the alcohol concerned. On the other hand, 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.
本発明に係る殺ウイルス用組成物は、メタケイ酸塩と対象物に接触させるための必要な基剤及び必要に応じて添加される上記殺菌剤のみを含むが、その他、必要に応じて、着色剤や香料、キレート剤など殺ウイルス作用に影響を及ぼさない任意的成分を含み得る。なお、メタケイ酸ナトリウムの水溶液はアルカリ性を示し、ｐＨ７付近の水溶液では沈殿を生じたり、殺ウイルス作用が失われたりするので、水溶液として用いる場合には中和の必要性はない。従って、本発明に係る組成物は中和に必要な塩酸、リン酸、硫酸などの酸は含まない。 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. In addition, since 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.
本発明に係る殺ウイルス剤又は殺ウイルス用組成物は、エンベロープの有無を問わず、各種のウイルスに作用する。対象となるウイルスは、例えば、ヘルペスウイルスであり、コロナウイルスであり、パルボウイルス、カリシウイルスであり、ネコ伝染性腹膜炎ウイルスであり、インフルエンザウイルスであり得る。 The virucidal agent or virucidal composition according to the present invention acts on various viruses regardless of the presence or absence of 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.
次に下記の実施例に基づき本発明についてさらに説明するが、本発明は下記の実施例に限られないのは言うまでもない。 Next, the present invention will be further described based on the following examples, but it is needless to say that the present invention is not limited to the following examples.
〔メタケイ酸ナトリウムの殺ウイルス作用〕
ネコパルボウイルスPLI-IV株、ネコカリシウイルスF9株、ネコヘルペスウイルス80-1株、ネコ伝染性腹膜炎ウイルス79−1146株、オーエスキー病ウイルスYamagata S81株を用いた。ネコパルボウイルス、ネコカリシウイルス、ネコヘルペスウイルスならびにオーエスキー病ウイルスは、ネコ腎由来株化細胞CRFKで、ネコ伝染性腹膜炎ウイルスはネコ胎仔由来株化細胞fcwf-4で増殖させた。[Virucidal action of sodium metasilicate]
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.
ウイルス液０.５mlに１.２mg/g濃度のメタケイ酸ナトリウム０.５mlを加え、室温で５分間反応させた。対照としてメタケイ酸ナトリウムの代わりに滅菌蒸留水を加えたウイルス液を同様に反応させた。処理した検体は１０倍階段希釈を行ない、細胞に接種してネコカリシウイルス、ネコヘルペスウイルス、ネコ伝染性腹膜炎ウイルスについては、２日間培養後、ウイルスによる細胞変性効果でウイルス感染の有無を判定し、５０％組織培養感染濃度(TCID50/ml)を求めた。ネコパルボウイルスについては、４日間培養後、細胞をトリプシンで剥離し、PBSで洗浄した。PBSに再浮遊後、１２穴高撥水性印刷スライドグラスに塗抹し、アセトン固定を行なった。その後、一次血清としてFPVワクチン接種ネコ血清を、二次血清として、FITC標識抗ネコIgGヤギ血清を用いた間接蛍光抗体法で感染の有無を判定し、TCID50/mlを求めた。その結果を表１に示す。To 0.5 ml of the virus solution, 0.5 ml of sodium metasilicate having a concentration of 1.2 mg / g was added and reacted at room temperature for 5 minutes. As a control, 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 of viral infection by the cytopathic effect of the virus 50% tissue culture infection concentration (TCID 50 / ml) was determined. For 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.
表１に示すように、ネコパルボウイルス、ネコカリシウイルス、ネコヘルペスウイルス、オーエスキー病ウイルスは、ウイルス液と等量の１.２mg/gのメタケイ酸ナトリウム水溶液で室温５分間反応させることで、完全に増殖が阻止された。ネコ伝染性腹膜炎ウイルスについては、上記４種類のウイルスに比べると効果が低いが、感染濃度は１万分の１にまで低下した。 As 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.
〔メタケイ酸ナトリウム水溶液の濃度と反応時間による殺ウイルス作用の変化〕
メタケイ酸ナトリウムの濃度による殺ウイルス作用を検討するため、ネコカリシウイルス、ネコヘルペスウイルスを用いた。メタケイ酸ナトリウムを１.２mg/g、０.６mg/g、０.１２mg/gの水溶液に調製し、ウイルス液０.５mlに、０.５mlのメタケイ酸ナトリウム水溶液を加え、室温で１分あるいは５分反応させた。１０倍階段希釈後、CRFK細胞に接種した。２日間培養後、細胞変性効果でウイルス感染の有無を判定し、TCID50/mlを求めた。その結果を表２に示した。[Changes in virucidal action by concentration of sodium metasilicate aqueous solution and reaction time]
Feline calicivirus and feline herpesvirus were used to examine the virucidal action by the concentration of sodium metasilicate. Prepare sodium metasilicate in aqueous solution of 1.2mg / g, 0.6mg / g, 0.12mg / g, add 0.5ml of sodium metasilicate aqueous solution to 0.5ml of virus solution and at room temperature for 1 minute or Reacted for 5 minutes. CRFK cells were inoculated after 10-fold serial dilution. After culturing for 2 days, the presence or absence of viral infection was determined by cytopathic effect, and TCID 50 / ml was determined. The results are shown in Table 2.
ネコカリシウイルスは０.６mg/gのメタケイ酸ナトリウム水溶液で１分間処理した場合、感染濃度が１万分の１以下に低下し、５分間処理で完全に増殖が阻止された。また、０.１２mg/gでは効果がみられなかった。一方、ネコヘルペスウイルスは、０.６mg/g、０.１２mg/gともに、効果がみられなかった。なお、１５mg/g濃度の水溶液ではCRFK細胞に対する細胞毒性が観察され、これらの各ウイルスに対する作用は観察できなかったが、当該濃度でもメタケイ酸ナトリウム水溶液の抗ウイルス作用が失われるものではない。 When feline calicivirus was treated with a 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.
〔殺ウイルス作用へのタンパク質の影響〕
タンパク質がメタケイ酸ナトリウムの殺ウイルス作用に与える影響を調べるため、ネコカリシウイルス液に牛胎仔血清を１v/v％、５v/v％、１０v/v％、２０v/v％濃度で加えたもの０.５mlと、１.２mg/gのメタケイ酸ナトリウム水溶液０.５mlを室温で５分間反応させた。対照として、メタケイ酸ナトリウム水溶液の代わりに、消毒薬として汎用されているピューラックス（商品名：６w/v％の次亜塩素酸ナトリウムを含む）を１％の次亜塩素酸ナトリウムを含むように希釈した溶液を加えたものを同様に反応させた。１０倍階段希釈後、CRFK細胞に接種し、２日間培養の後、細胞変性効果でウイルス感染の有無を判定し、TCID50/mlを求めた。その結果を表３に示す。[Influence of protein on virucidal action]
To examine the effect of protein on the virucidal action of sodium metasilicate, fetal calicivirus solution with fetal calf serum added at 1 v / v%, 5 v / v%, 10 v / v%, 20 v / v% concentration 0 0.5 ml and 0.5 ml of a 1.2 mg / g sodium metasilicate aqueous solution were reacted at room temperature for 5 minutes. As a control, instead of sodium metasilicate aqueous solution, 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.
ネコカリシウイルスは、２０%にまで牛胎仔血清が混じった状態でも１.２mg/gメタケイ酸ナトリウム水溶液で完全に増殖が阻止された。一方、１％の次亜塩素酸ナトリウムを含むように希釈したピューラックスでは、１％の濃度に牛胎仔血清を加えただけで、殺ウイルス作用が阻害された。 The feline calicivirus was completely inhibited by the 1.2 mg / g sodium metasilicate aqueous solution even in a state where the fetal calf serum was mixed to 20%. On the other hand, Pulux diluted to contain 1% sodium hypochlorite inhibited the virucidal action only by adding fetal calf serum to a concentration of 1%.
以上の結果から、約１分以上、約０.３mg/gのメタケイ酸ナトリウム水溶液と接触させることで、ネコパルボウイルスやネコカリシウイルス、ネコヘルペスウイルスに対して殺ウイルス作用が認められた。また、ネコ伝染性腹膜炎ウイルスに対しても、これらのウイルスに比べて弱いながらも、殺ウイルス作用が認められた。そして、メタケイ酸ナトリウム水溶液の殺ウイルス作用は、タンパク質の影響を受けにくいことが示された。 From the above results, a virucidal action was observed against feline parvovirus, feline calicivirus, and feline herpesvirus by contact with about 0.3 mg / g sodium metasilicate aqueous solution for about 1 minute or longer. Moreover, although it was weak against the feline infectious peritonitis virus compared with these viruses, the virucidal action was recognized. And it was shown that the virucidal action of the sodium metasilicate aqueous solution is hardly affected by the protein.
〔殺菌剤入りの殺ウイルス剤の殺ウイルス作用〕
次に、下記の組成からなる殺ウイルス剤（メタケイ酸ナトリウムとして９.０mg/gを含む）の殺ウイルス効果を調べた。殺ウイルス剤とウイルス液を表４に示す容量比で混合し、室温で１分間又は５分間接触させた。対照として蒸留水とウイルス液を５０％容量比で混合し、同様に接触させた。また、１％の次亜塩素酸ナトリウムを含むように希釈したピューラックスの希釈溶液についても同様に接触させ、実施例１と同様にしてウイルス力価を求めた。その結果を表４及び表５に示した。表４に示すように実施例２の殺ウイルス剤の約２倍希釈液（４.５mg/gのメタケイ酸ナトリウム水溶液）は１分間の接触で殺ウイルス作用を示した。殺菌剤を併用した場合にはメタケイ酸ナトリウムの殺ウイルス効果が低下する傾向にあったが、殺菌剤を併用した場合でも、メタケイ酸ナトリウムの殺ウイルス効果は失われることはなかった。[Virucidal action of a virucidal agent containing a bactericidal agent]
Next, the virucidal effect of a virucidal agent having the following composition (containing 9.0 mg / g as sodium metasilicate) was examined. Viralicide and virus solution were mixed at a volume ratio shown in Table 4 and contacted at room temperature for 1 minute or 5 minutes. As a control, distilled water and virus solution were mixed at a volume ratio of 50% and contacted in the same manner. In addition, a diluted solution of Pulux diluted to contain 1% sodium hypochlorite was also brought into contact in the same manner, and the virus titer was determined in the same manner as in Example 1. The results are shown in Tables 4 and 5. 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.
（殺菌剤入り殺ウイルス剤）
無水メタケイ酸ナトリウム ０.９２ｇ
ポリオクチルポリアミノエチルグリシン ０.０６ｇ
ポリオキシエチレンアルキルエーテル ０.０４ｇ
水 １００.９０ｇ(Viricide with fungicide)
0.92 g of anhydrous sodium metasilicate
Polyoctyl polyaminoethylglycine 0.06g
Polyoxyethylene alkyl ether 0.04g
100.90 g of water
〔糞便中のウイルスに対する効果〕
０.１ｇのイヌ糞便にネコパルボウイルス106TCID50を加え、混合後、０.９mlの６.０mg/gメタケイ酸ナトリウム水溶液又は１％の次亜塩素酸ナトリウムを含むように希釈したピューラックス溶液０.９mlを加えて室温で５分間反応させた。対照として、滅菌蒸留水を同様に反応させた。１０倍階段希釈後、CRFK細胞に接種し、４日間培養後、間接蛍光抗体法でウイルス感染の有無を判定し、TCID50/mlを求めた。その結果を表６に示す。[Effects on viruses in feces]
Purax solution diluted to contain 0.9 ml of 6.0 mg / g sodium metasilicate aqueous solution or 1% sodium hypochlorite after adding feline parvovirus 10 6 TCID 50 to 0.1 g of dog feces and mixing. 0.9 ml was added and reacted at room temperature for 5 minutes. As a control, sterilized distilled water was reacted in the same manner. After 10-fold serial dilution, CRFK cells were inoculated, cultured for 4 days, the presence or absence of viral infection was determined by the indirect fluorescent antibody method, and TCID 50 / ml was determined. The results are shown in Table 6.
糞便に加えたネコパルボウイルスは６.０mg/gのメタケイ酸ナトリウム水溶液と５分接触させることで完全に増殖が阻止された。また、１％ピューラックスでも同様の阻止がみられた。 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.
〔布に付着したウイルスに対する効果〕
布に付着したウイルスにメタケイ酸ナトリウムが殺ウイルス作用を示すかどうかを検討した。ネコカリシウイルスのウイルス液１mlに２cm×２cmの滅菌したタオルを浸し、ウイルス液をしっかりと浸み込ませた。その後、１.２mg/gのメタケイ酸ナトリウム水溶液又は培養液の５mlに３０分間、浸漬した。１０倍階段希釈後、CRFK細胞に接種し、２日間培養後、細胞変性効果でウイルス感染の有無を判定し、TCID50/mlを求めた。対照として、ウイルス液のみ、ウイルス液１mlと１.２mg/gメタケイ酸ナトリウム水溶液５mlを反応させたものを用いた。結果を表７に示す。タオルに付着したウイルスもメタケイ酸ナトリウム水溶液に３０分間浸漬することで完全に増殖が阻止された。
It was investigated whether sodium metasilicate exerted a virucidal action on the virus attached to the cloth. A 2 cm × 2 cm sterilized towel was soaked in 1 ml of the feline calicivirus virus solution, so that the virus solution was firmly immersed. Then, it was immersed in 5 ml of 1.2 mg / g sodium metasilicate aqueous solution or culture solution for 30 minutes. After 10-fold serial dilution, CRFK cells were inoculated, cultured for 2 days, and the presence or absence of virus infection was determined by cytopathic effect, and TCID 50 / ml was determined. As a control, only 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.
〔インフルエンザウイルスに対する殺ウイルス効果〕
ワクチンとして用いられているＡ型インフルエンザウイルスA/panama/2007/99（H3N2）を用いた。ウイルス液と等量の1.2mg/gのメタケイ酸ナトリウム水溶液で室温５分間反応させた。10倍階段希釈後、MDCK細胞に接種し、４日間培養後、細胞変性効果でウイルス感染の有無を判定し、TCID50/mlを求めた。対照として、ウイルス液と等量の滅菌蒸留水を反応させたものを用いた。その結果を表８に示す。インフルエンザウイルスも増殖が阻止された。
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. After 10-fold serial dilution, 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. 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.
上記に用いられたネコパルボウイルスは、パルボウイルス科パルボウイルス属に属するウイルスであり、エンベロープを有しない。ネコカリシウイルスは、カリシウイルス科ベシウイルス属に属するウイルスであり、エンベロープを有しない。ネコヘルペスウイルス（ネコウイルス性鼻気管炎ウイルス）やオーエスキー病ウイルスは、ヘルペスウイルス科バリセロウイルス属に属するウイルスであり、エンベロープを有する。ネコ伝染性腹膜炎ウイルスはコロナウイルス科アルファコロナウイルス属に属するウイルスであり、エンベロープを有する。 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.
同じ科や同じ属に属するウイルスは物理化学的性状が似通っているので、殺ウイルス剤に対する感受性は同じと考えられている。従って、パルボウイルス科パルボウイルス属に属するイヌパルボウイルスやブタパルボウイルス、パルボウイルス科エリスロウイルス属に属するB19ウイルス（ヒトに感染）、カリシウイルス科ベシウイルス属に属するノロウイルス（ヒトに感染）、ヘルペスウイルス科バリセロウイルス属に属する水痘・帯状疱疹ウイルス（ヒトに感染）、コロナウイルス科アルファコロナウイルス属に属する豚伝染性胃腸炎ウイルスなどにも、メタケイ酸ナトリウムは有効であると結論づけられる。もっともメタケイ酸ナトリウムはエンベロープの有無に関係なく、インフルエンザウイルスなど各種のウイルスに殺ウイルス作用があると考えられる。 Viruses belonging to the same family and the same genus are considered to have the same susceptibility to virucidal agents because they have similar physicochemical properties. 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 It can be concluded that 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. However, it is considered that sodium metasilicate has a virucidal action on various viruses such as influenza virus regardless of the presence or absence of an envelope.
本発明によると、広範囲の殺ウイルススペクトルを有し、かつ、取り扱いが容易な殺ウイルス剤が提供される。 According to the present invention, a virucidal agent having a broad virucidal spectrum and easy to handle is provided.
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