US20150010604A1 - Bactericidal agent composition - Google Patents

Bactericidal agent composition Download PDF

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Publication number
US20150010604A1
US20150010604A1 US14/377,315 US201314377315A US2015010604A1 US 20150010604 A1 US20150010604 A1 US 20150010604A1 US 201314377315 A US201314377315 A US 201314377315A US 2015010604 A1 US2015010604 A1 US 2015010604A1
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Prior art keywords
bactericidal
ultrafine bubbles
component
bactericidal component
agent composition
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Inventor
Miwa Ishii
Toru Oka
Yoshimitsu Nakayama
Masumi Torii
Masaru Sugimori
Shogo Takashiba
Hiroshi Maeda
Fumi Mineshiba
Kimito Hirai
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Sunstar Inc
Sunstar Engineering Inc
Okayama University NUC
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Sunstar Inc
Sunstar Engineering Inc
Okayama University NUC
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Assigned to SUNSTAR ENGINEERING INC. reassignment SUNSTAR ENGINEERING INC. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: ISHII, MIWA, OKA, TORU, TORII, MASUMI, NAKAYAMA, YOSHIMITSU
Assigned to SUNSTAR INC. reassignment SUNSTAR INC. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: SUGIMORI, MASARU
Assigned to NATIONAL UNIVERSITY CORPORATION OKAYAMA UNIVERSITY reassignment NATIONAL UNIVERSITY CORPORATION OKAYAMA UNIVERSITY ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: HIRAI, Kimito, TAKASHIBA, SHOGO, MAEDA, HIROSHI, MINESHIBA, Fumi
Publication of US20150010604A1 publication Critical patent/US20150010604A1/en
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    • 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
    • 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
    • A01N25/00—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests
    • 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
    • A01N25/00—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests
    • A01N25/02—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests containing liquids as carriers, diluents or solvents
    • 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
    • A01N25/00—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests
    • A01N25/34—Shaped forms, e.g. sheets, not provided for in any other sub-group of this main group
    • 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
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/34—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom
    • A01N43/36—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom five-membered rings
    • 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
    • A01N59/12—Iodine, e.g. iodophors; Compounds thereof
    • 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
    • A01N65/00—Biocides, pest repellants or attractants, or plant growth regulators containing material from algae, lichens, bryophyta, multi-cellular fungi or plants, or extracts thereof
    • A01N65/08—Magnoliopsida [dicotyledons]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/02—Local antiseptics

Definitions

  • the present invention relates to a novel bactericidal agent composition capable of sterilizing in the presence of various kinds of organic contaminations in the environment or sterilizing bacteria in biofilms by means of using water containing ultrafine bubbles, a method for producing the bactericidal agent composition, and a sterilization method using the bactericidal agent composition.
  • Bactericidal agents are used extensively in all areas such as engineering, cosmetics, food processing, pharmaceuticals, agriculture, and dairy husbandry.
  • the types of bactericidal agents are quite versatile and examples used in medical and food fields include chlorine sterilizers, iodine sterilizers, peroxide sterilizers, aldehyde sterilizers, phenolic sterilizers, biguanide sterilizers, mercury sterilizers, alcoholic sterilizers, quaternary ammonium salt sterilizers, and amphoteric surfactant sterilizers.
  • biofilms which can sometimes pose serious problems both in the living environment of humans and in the industry. Take, for example, a dwelling environment; biofilms can be a cause of discomfort if they produce slimes, clogging or malodor in toilets, kitchens, bathrooms, etc. Another potential cause of infections is the bacteria in biofilms formed in water-circulating bathtubs in hot spa facilities and the like.
  • biofilms on production lines in plants can be another cause of microbial contamination.
  • biofilms formed in tubes for dialysis and other applications, as well as in medical devices such as endoscopes and contact lenses can be a source of infection; diseases can also be caused by biofilm formation in skin and other human tissues.
  • endoscopes and contact lenses can be a source of infection; diseases can also be caused by biofilm formation in skin and other human tissues.
  • dental plaques can cause dental caries and periodontal disease.
  • biofilms formed on perishable goods such as vegetables, as well as materials for processed foods and cooking utensils are potential causes of putrefaction and food poisoning. These problems are currently coped by specifying bactericidal concentrations for actual use that are much higher than those found in the laboratory.
  • Patent Documents 1, 2 and 3 It was proposed that penetrability into biofilms be improved by methods characterized by additional use of anionic surfactants (Patent Documents 1, 2 and 3). These known techniques, however, had their own problems. For example, in actual use, contaminating by organic substances is assumed and bactericidal concentrations are specified that are much higher than those found in the laboratory; however, even such higher concentrations were unable to kill the bacteria found in excessive contaminations or biofilms and, what is more, they were undesirable from the viewpoints of human body and environmental safety. Another problem was that fatty acid esters of glycerol which would not lose bactericidal or antibacterial activity in the contamination by organic substances had no antibacterial activity against Gram-negative bacteria (Non-Patent Document 1).
  • ethylenediaminetetraacetic acid a chelatant having bactericidal power against Gram-negative bacteria
  • Patent Documents 4, 5 and 6 ethylenediaminetetraacetic acid had a problem with the latitude of formulation in that only limited combinations of formulations was permitted, as exemplified by the case where it reacted with hypochlorous acid or salts thereof and the available chlorine concentration decreased to result in a lower bactericidal power.
  • Patent Documents 1, 2 and 3 it was proposed that penetrability into biofilms be improved by methods characterized by additional use of anionic surfactants (Patent Documents 1, 2 and 3) but they also had a problem with the latitude of formulation, as exemplified by the attenuation of bactericidal power due to an electrical interaction that occurred when they were used in combination with cationic sterilizers.
  • Patent Document 1 JP 2006-69909A
  • Patent Document 2 JP 2006-182663A
  • Patent Document 3 JP 2006-312588A
  • Patent Document 4 JP 1997-278610 A
  • Patent Document 5 JP2003-528820 A
  • Patent Document 6 JP1987-269673 A
  • Non-Patent Document 1 Koshohin Bofu/Sakkinzai no Kagaku (Japanese translation of “Cosmetic and Drug Preservation: Principles and Practice”), ed. by John J. Kabara, translated by Koichi Yoshimura & Hirofumi Takigawa, published by Fragrance Journal Ltd. on Apr. 10, 1990, pp. 249-263
  • the present invention has as its objectives providing a bactericidal agent composition which can exhibit an excellent bactericidal effect in the presence of an organic substance and against biofilms, a method for producing the bactericidal agent composition, and a sterilization method using the bactericidal agent composition.
  • the present invention relates to a bactericidal agent composition which comprises ultrafine bubbles having a most frequent particle diameter of 500 nm or less and a bactericidal component.
  • the “density of most frequent particles” among the ultrafine bubbles which is the number per milliliter (mL) of particles having the most frequent particle diameter is 1 ⁇ 10 4 particles or more.
  • the “total particle density” which is the total number of ultrafine bubbles per mL is 1 ⁇ 10 6 or more.
  • the density of ultrafine bubbles each having a particle diameter of 1000 nm or less which is the number per mL of ultrafine bubbles having a particle diameter of 1000 nm or less is preferably 1 ⁇ 10 6 particles or more.
  • the interior of the above-described ultrafine bubbles may be filled with one or more gases selected from among air, oxygen, hydrogen, nitrogen, carbon dioxide, argon, neon, xenon, fluorinated gases, ozone, and inert gases.
  • the bactericidal component which is used in the present invention may be an iodine bactericidal component, a peroxide bactericidal component, an aldehyde bactericidal component, a phenolic bactericidal component, a biguanide bactericidal component, a mercury bactericidal component, an alcoholic bactericidal component, a quaternary ammonium salt bactericidal component, an amphoteric surfactant bactericidal component, and a naturally derived bactericidal component.
  • the present invention provides a method for producing a bactericidal agent composition which comprises mixing water containing ultrafine bubbles having a most frequent particle diameter of 500 nm or less with a bactericidal component.
  • the present invention also provides a method for producing a bactericidal agent composition which comprises generating ultrafine bubbles having a most frequent particle diameter of 500 nm or less within water containing a bactericidal component.
  • the density of most frequent particles among the ultrafine bubbles are 1 ⁇ 10 4 particles or more, with 1 ⁇ 10 5 particles or more being further preferred.
  • the total fine particle density and the density of ultrafine bubbles each having a particle diameter of 1000 nm or less are each 1 ⁇ 10 6 particles or more.
  • the present invention provides a sterilization method using the bactericidal agent composition according to its first aspect; in particular, it provides a sterilization method comprising a step in which the bactericidal agent composition according to its first aspect is brought into contact with a biofilm.
  • biofilm refers to higher structure entities formed by microorganisms and may be exemplified by films formed through binding with extracellular polymeric substances (EPS) such as polysaccharides. More specific examples of biofilms include those which were already mentioned above, i.e., biofilms formed in residential toilets, kitchens and bathrooms, biofilms formed in water-circulating bath tubs as in hot spa facilities, biofilms formed in various kinds of piping such as sewage pipes, biofilms formed on ship bottoms, biofilms formed on production lines in plants, biofilms formed in tubes for dialysis and other applications, biofilms formed in medical devices such as endoscopes and contact lenses, biofilms formed on the skin or in the oral cavity of human body, biofilms formed on perishable goods such as vegetables and materials for processed foods, and biofilms formed on cooking utensils.
  • EPS extracellular polymeric substances
  • a bactericidal agent composition which can exhibit an excellent bactericidal effect in the presence of an organic substance and against biofilms, and a sterilization method using the same.
  • FIG. 1 is a graph showing the result of measuring the particle size distribution of bubbles in water containing ultrafine bubbles (since the apparatus's upper limit of detection was exceeded, water as the analyte was diluted with purified water and the resulting data of measurement was multiplied by the dilution ratio to provide the result shown in Fig.).
  • FIG. 2 is a graph showing the result of measuring the particle size distribution of bubbles in purified water as specified in the Japanese Pharmacopoeia.
  • the ultrafine bubbles to be used in the present invention have a most frequent particle diameter of 500 nm or less, preferably a most frequent particle diameter of 300 nm or less, more preferably a most frequent particle diameter of 150 nm or less, and most preferably a most frequent particle diameter of 110 nm or less; the density of most frequent particles is preferably 1 ⁇ 10 4 particles or more, more preferably 5 ⁇ 10 4 particles or more, even more preferably 5 ⁇ 10 5 particles or more, still more preferably 5 ⁇ 10 6 particles or more, yet more preferably 1 ⁇ 10 7 particles or more, still even more preferably 5 ⁇ 10 7 particles or more, yet more preferably 1 ⁇ 10 8 particles or more, even more preferably 5 ⁇ 10 8 particles or more, and most preferably 7 ⁇ 10 8 particles or more.
  • the density of ultrafine bubbles having a particle diameter of 1000 nm or less and the total particle density are each preferably 1 ⁇ 10 6 particles or more, more preferably 4 ⁇ 10 6 particles or more, even more preferably 4 ⁇ 10 7 particles or more, still more preferably 1 ⁇ 10 8 particles or more, yet more preferably 4 ⁇ 10 8 particles or more, still even more preferably 1 ⁇ 10 9 particles or more, yet more preferably 3 ⁇ 10 9 particles or more, even more preferably 5 ⁇ 10 9 particles or more, still more preferably 7 ⁇ 10 9 particles or more, yet more preferably 1 ⁇ 10 10 particles or more, even more preferably 2 ⁇ 10 10 particles or more, and most preferably 4 ⁇ 10 10 particles or more.
  • total particle density is synonymous with the density of ultrafine bubbles having a particle diameter of 1000 nm or less.
  • bubbles larger than 1000 nm are seldom found, so the two terms are used as synonyms.
  • the particle diameter of the ultrafine bubbles to be used in the present invention is so small that it cannot be measured correctly with an ordinary particle size distribution analyzer.
  • numerical values are employed that were obtained by measurements with the nanoparticle size analyzing system NanoSight Series (product of NanoSight Ltd.)
  • the nanoparticle size analyzing system NanoSight Series (product of NanoSight Ltd.) measures the velocity of nanoparticles moving under Brownian motion and calculates the diameters of the particles from the measured velocity. A most frequent particle diameter can be verified from the size distribution of the particles present and refers to the particle diameter at which the number of particles assumes a maximum value.
  • Water to be used in the present invention can be selected from, but is not limited to, tap water, purified water, ion-exchanged water, pure water, ultrapure water, deionized water, distilled water, buffer solutions, clean water, natural water, filtered water, highly pure water, potable water, and electrolyzed water.
  • Water-soluble solvents such as alcohols, glycols, glycerol, ethers, ketones, and esters may also be added.
  • the zeta potential on the surfaces of ultrafine bubbles affects the stability of the bubbles.
  • the surfaces of the ultrafine bubbles used in the present invention are electrically charged to produce a zeta potential of 5 mV or higher, preferably 7 mV or higher, more preferably 10 mV or higher, even more preferably 20 mV or higher, still more preferably 25 mV or higher, and most preferably 30 mV or higher, in absolute value.
  • the ultrafine bubbles to be used in the present invention can be generated by any known means, such as the use of a static mixer, the use of a venturi tube, cavitation, vapor condensation, sonication, swirl formation, dissolution under pressure, or fine pore formation.
  • a preferred method of bubble generation is by forming a gas-liquid mixture and shearing it.
  • An aqueous solution of the bactericidal component may be treated with a suitable apparatus to generate ultrafine bubbles in it, whereby the composition of the present invention can be produced that has the bactericidal component dissolved in the water.
  • the composition of the present invention can be produced by dissolving the bactericidal component in water containing ultrafine bubbles.
  • the aforementioned water containing ultrafine bubbles may have the most frequent particle diameter and density that have been specified above.
  • the bactericidal component may be dispersed in water containing ultrafine bubbles.
  • ultrafine bubbles may be generated in a dispersion having the bactericidal component dispersed in water.
  • the bactericidal component may be added to water containing ultrafine bubbles and then dispersed in the water.
  • the expression of “comprising the bactericidal component” embraces two cases, one where the bactericidal component is dissolved in water and one where it is dispersed in water.
  • the bactericidal component to be used in the present invention may be a chlorine bactericidal component, an iodine bactericidal component, a peroxide bactericidal component, an aldehyde bactericidal component, a phenolic bactericidal component, a biguanide bactericidal component, a mercury bactericidal component, an alcoholic bactericidal component, a quaternary ammonium salt bactericidal component, an amphoteric surfactant bactericidal component, or a naturally derived bactericidal component.
  • Examples of the chlorine bactericidal component include sodium hypochlorite, chlorine, chloroisocyanuric acid, etc.
  • iodine bactericidal component examples include iodine, povidone iodine, nonoxynol iodine, phenoxy iodine, etc.
  • peroxide bactericidal component examples include hydrogen peroxide, potassium permanganate, ozone, strongly acidic water, etc.
  • aldehyde bactericidal component examples include glutaraldehyde, phtharal, formaldehyde, etc.
  • phenolic bactericidal component examples include isopropylmethylphenol, thymol, eugenol, triclosan, cresol, phenol, chlorocresol, parachloromethacresol, parachlorometaxylenol, ortho phenylphenol, alkyl esters of paraoxybenzoic acid, resorcin, hexachlorophene, salicylic acid, salts thereof, etc.
  • Examples of the biguanide bactericidal component include chlorhexidine, chlorhexidine gluconate, chlorhexidine hydrochloride, etc.
  • mercury bactericidal component examples include mercurochrome, mercury (II) chloride, thimerosal, etc.
  • the alcoholic bactericidal component may be exemplified by ethanol, isopropanol, etc.
  • quaternary ammonium salt bactericidal component examples include cetylpyridinium chloride, benzethonium chloride, benzalkonium chloride, dequalinium chloride, etc.
  • amphoteric surfactant bactericidal component examples include N-alkyldiaminoethylglycines (e.g. N-lauryldiaminoethylglycine and N-myristyldiethylglycine), N-alkyl-N-carboxymethylammonium betaine, 2-alkyl-1-hydroxyethyl imidazoline betaine sodium, etc.
  • the bactericidal component to be used in the present invention may also be the naturally derived bactericidal component described below.
  • Examples of the naturally derived bactericidal component include: plant derived materials such as Hinokitiol, anethole, anise oil, borneol, camphor, carvone, cassia oil, Chenopodiaceae oil, cineol, citral, citronellal, eugenol, pinene, geraniol, lemon oil, linalol, menthol, orange oil, saflol, thymol, etc.; animal derived materials such as chitin and chitosan prepared from the shells of crustaceans, and fired seashell powders obtained by firing the shells of scallops and oysters; microbial materials such as polylysine; and enzymatic materials such as lysozyme.
  • plant derived materials such as Hinokitiol, anethole, anise oil, borneol, camphor, carvone, cassia oil, Chenopodiaceae oil, cineol, citral,
  • Antibacterial peptides that organisms produce in order to defend themselves against external microorganisms may also be used and they include, for example, histatin, defensins, lactoferrin, lactoferricin which is a decomposition product of lactoferrin, magainin, cecropin, melititin, etc. Since these peptides are innately produced by organisms, they have extremely small side effect or inhibitory actions on the living body. In addition, it would be expected that by simply cleaning the body with water containing the ultrafine bubbles, the bactericidal effect of the antibacterial peptides on the surface of the skin is so much enhanced that adequate bactericidal effects can be obtained without using additional bactericidal agents.
  • Antibacterial plant extracts can also be used as the naturally derived antibacterial component. Specific examples include: grapefruit seed extract, as well as plant extracts from; Kochia scoparia, etc. of the family Chenopodiaceae; Belamcanda chinensis , etc. of the family Iridaceae; Hypericum perforatum of the family Hypericaceae; Boswellia carterii Birdw, Cedronella canariensis , etc. of the family Burseraceae; Adenophora triphylla var.
  • an iodine bactericidal component such as povidone iodine
  • a biguanide bactericidal component such as chlorhexidine gluconate
  • quaternary ammonium salt bactericidal component such as benzalkonium chloride
  • plant extract such as grapefruit seed extract.
  • the amount of the bactericidal component to be used varies with its kind, use, etc. While the preferred amount can be determined appropriately by experiment, the bactericidal component can generally be used in amounts ranging from 10 to 0.00001 wt % of the bactericidal agent composition.
  • any optional component that is appropriate for a specific dosage form of the bactericidal agent composition of the present invention may be incorporated in it on the condition that the effects of the present invention will not be impaired; examples of such optional component are a wetting agent, a thickening agent, a stabilizer, a pH modifier, an antiseptic, a sweetener, a fragrance, a surfactant, an active ingredient, a colorant, a chelating agent, a UV absorber, a bleaching agent, an antifoaming agent, an enzyme, etc.
  • a further improvement in the bactericidal effect can be expected by incorporating an auxiliary agent as a potentiator. If povidone iodine is used as the bactericidal component, a component that enhances its stability at low concentration may also be incorporated (JP 1993-43891A).
  • sugar alcohols and polyhydric alcohols such as butylene glycol, ethylene glycol, xylit, maltit, and lactit may be used in addition to the above-described component (B).
  • Exemplary thickening agents include cellulosic binders (e.g. carboxymethylcellulose sodium, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropylmethyl cellulose, hydroxymethylethyl cellulose, and methyl cellulose), xanthan gum, carrageenan, guar gum, sodium alginate, cationized cellulose, montmorillonite, gelatin, sodium polyacrylate, etc.
  • cellulosic binders e.g. carboxymethylcellulose sodium, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropylmethyl cellulose, hydroxymethylethyl cellulose, and methyl cellulose
  • xanthan gum e.g. carboxymethylcellulose sodium, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropylmethyl cellulose, hydroxymethylethyl cellulose, and methyl cellulose
  • carrageenan e.g. carboxymethylcellulose sodium, hydroxyeth
  • Exemplary pH modifiers include phthalic acid, phosphoric acid, citric acid, succinic acid, acetic acid, fumaric acid, malic acid, and carbonic acid, as well as salts thereof with potassium, sodium, and ammonium; ribonucleic acid and salts thereof; sodium hydroxide, etc.
  • antiseptics include benzoates such as sodium benzoate, alkyldiaminoethylglycine hydrochloride, potassium sorbate, etc.
  • Exemplary sweeteners include saccharin sodium, aspartame, stevioside, Stevia rebaudiana extract, para-methoxycinnamic aldehyde, neohesperidin dihydrochalcone, perillartin, etc.
  • fragrances include: natural fragrances such as eucalyptus oil, wintergreen oil, cassia oil, clove oil, thyme oil, sage oil, basil oil, cardamom oil, coriander oil, spearmint oil, orange oil, lemon oil, mandarin oil, lime oil, grapefruit oil, yuzu oil, sweetie (orobranco) oil, lavender oil, rosemary oil, laurel oil, chamomile oil, caraway oil, marjoram oil, celery oil, bay oil, origanum oil, pine needle oil, neroli oil, lemon grass oil, rose oil, jasmine oil, patchouli oil, iris concrete, rose absolute, orange flower absolute, vanilla absolute, mango absolute, patchouli absolute, ginger oleoresin, pepper oleoresin, capsicum oleoresin, and Capsicum annuum Linne extract; fragrances prepared by processing the above-mentioned natural fragrances (as by cutting the initial or last run, fractionation, liquid-liquid extraction, rendering
  • Exemplary surfactants include nonionic surfactants, anionic surfactants, cationic surfactants, and amphoteric surfactants.
  • Anionic surfactants include, for example, sodium alkyl sulfates such as sodium lauryl sulfate and sodium myristyl sulfate; acyl sarcosine salts such as sodium lauryl sarcosinate and sodium myristyl sarcosinate; sodium dodecylbenzenesulfonate, sodium hydrogenated coconut fatty acid monoglyceride monosulfate, and sodium lauryl sulfoacetate; N-acylglutamates such as N-acyl glutamates and sodium N-palmitoyl glutamate; as well as sodium salt of N-methyl-N-acyl taurine, sodium salt of N-methyl-N-acyl alanine, and sodium a-olefin sulfonate.
  • Exemplary pigments include Blue No. 1, Green No. 3, Yellow No. 4, Red No. 105, etc.
  • auxiliary agent as a bactericidal potentiator examples include anionic surfactants, nonionic surfactants, amphoteric surfactants, cationic surfactants, and sugar alcohols that enhance the penetration into biofilms; an exemplary anionic surfactant is sodium lauryl sulfate, and exemplary sugar alcohols include erythritol, xylitol, sorbitol, etc.
  • Exemplary cationic surfactants include: alkyl trimethyl ammonium salts such as stearyl trimethyl ammonium chloride and lauryl trimethyl ammonium chloride, alkyl pyridinium salts such as cetylpyridinium chloride, dialkyl dimethyl ammonioum salts such as distearyl dimethyl ammonium chloride, poly(N,N′-dimethyl-3,5-methylenepiperidinium chloride), alkyl quaternary ammonium salts, alkyl dimethyl benzyl ammonium salts, alkyl isoquinolinium salts; dialkyl morpholinium salts, POE-alkyl amines, alkyl amine salts, polyamine fatty acid derivatives; POE-amine fatty acid derivatives; polyamine fatty acid derivatives, amyl alcohol fatty acid derivatives, benzalkonium chloride, and benzethonium chloride.
  • alkyl trimethyl ammonium salts such as stearyl
  • nonionic surfactant examples include polyoxyethylene alkyl ethers, polyoxyethylene polyoxypropylene alkyl ethers, polyoxyethylene alkylphenyl ethers, polyglycerol esters of fatty acids, sugar esters of fatty acids, fatty acid alkanolamides, alkyl amine oxides, alkyl amide amine oxides, etc.
  • Exemplary chelating agent include alkaline builders such as sodium tripolyphosphate, sodium metasilicate, sodium carbonate, sodium hydroxide, and potassium hydroxide, as well as ethylenediaminetetraacetate (EDTA), N-hydroxyethyl-ethylenediaminetriacetate (HEDTA), and triethanolamine.
  • alkaline builders such as sodium tripolyphosphate, sodium metasilicate, sodium carbonate, sodium hydroxide, and potassium hydroxide, as well as ethylenediaminetetraacetate (EDTA), N-hydroxyethyl-ethylenediaminetriacetate (HEDTA), and triethanolamine.
  • UV absorbers may be benzophenone-based (e.g. 2-hydroxybenzophenone and 2,4-dihydroxybenzophenone), salicylate-based (e.g. phenyl salicylate and 2,4-di-t-butylphenyl-3,5-di-t-butyl-4-hydroxybenzoate), benzotriazole-based [(2′-hydroxyphenyl) benzotriazole and (2′-hydroxy-5′-methylphenyl)benzotriazole], acrylate-based [ethyl-2-cyano-3,3-diphenyl acrylate and methyl-2-carbomethoxy-3-(paramethoxybenzyl)acrylate], and so forth.
  • benzophenone-based e.g. 2-hydroxybenzophenone and 2,4-dihydroxybenzophenone
  • salicylate-based e.g. phenyl salicylate and 2,4-di-t-butylphenyl-3,5-di-t-buty
  • Exemplary antifoaming agents include silicones (e.g. dimethyl polysiloxane), mineral oils (e.g. spindle oil and kerosene), and metal soaps having 12-22 carbon atoms (e.g. calcium stearate).
  • silicones e.g. dimethyl polysiloxane
  • mineral oils e.g. spindle oil and kerosene
  • metal soaps having 12-22 carbon atoms e.g. calcium stearate
  • Exemplary enzymes include proteases, lipases, amylases, cellulases, oxidases, etc.
  • Ultrafine bubbles were generated in purified water (Japanese Pharmacopoeia) using BUVITAS of KYOWA KISETSU which was a device for generating ultrafine bubbles by the gas-liquid mix and shear method.
  • the particle diameters of the generated ultrafine bubbles were measured with the nanoparticle size analyzing system NanoSight Series (product of NanoSight Ltd.)
  • NanoSight Series product of NanoSight Ltd.
  • FIG. 1 The horizontal axis of the graph in FIG.
  • FIG. 1 represents the particle diameter in nanometers and the vertical axis represents the number of ultrafine bubbles particles per millimeter (10 8 /mL).
  • FIG. 2 shows the result of a measurement of fine bubbles in the purified water of the Japanese Pharmacopoeia.
  • the water containing the generated ultrafine bubbles had a most frequent particle diameter of 77 nm; the particle density at the most frequent particle diameter was 7.44 ⁇ 10 8 per milliliter and the total particle density was 4.11 ⁇ 10 10 per milliliter.
  • the purified water of the Japanese Pharmacopoeia had such low particle densities that the size distribution was not a normal distribution; the result of the measurement was therefore attributed to noise.
  • water containing ultrafine bubbles were prepared by the same method as described above, and the blanks as Comparative Examples used the purified water of the Japanese Pharmacopoeia in place of the water containing ultrafine bubbles.
  • test was conducted in accordance with AOAC Official Method 964.02 Testing Disinfectants against Pseudomonas aeruginosa.
  • the water prepared as described above to contain oxygen-filled ultrafine bubbles or the purified water of the Japanese Pharmacopoeia was used to dilute povidone iodine such that it was conditioned to 100 mg/L.
  • a cryopreserved bacterial strain ( Pseudomonas aeruginosa NBRC13275) was grown in a tryptic soy agar (Difco; hereinafter referred to as TSA medium) at 36 ⁇ 1° C. for 18-24 hours.
  • the grown cells were transplanted into a tryptic soy broth (Difco; hereinafter referred to as TSB medium) where they were cultured at 36 ⁇ 1° C. for 18-24 hours.
  • the liquids of the thus cultured cells were conditioned with a TSB medium to an approximate value of 10 6 CFU/mL and the resulting liquids were used as test bacterial liquids.
  • a sterile bioassay cup (stainless steel Penicillin Cup 441-01 made by Sogo Rikagagu glass; hereinafter designated as a carrier) was placed in a 100-mL beaker, into which test bacterial liquids were poured in such amounts that the carrier would be completely immersed (ca. 30-40 mL). After allowing the beaker to stand for 10-15 minutes, the carrier was transferred onto a Petri dish with sterile filter paper spread on the bottom and by allowing the Petri dish to stand at 36 ⁇ 1° C. for 40 ⁇ 2 minutes, the bacterial cells and the organic substance derived from the mediums were dried and adhered to the carrier.
  • a carrier stainless steel Penicillin Cup 441-01 made by Sogo Rikagagu glass
  • test liquids preliminarily held at 25 ⁇ 2° C. were each dispensed in 10 mL into centrifugal tubes having a capacity of 50 mL; using a hook of platinum wire, the carriers to which the test bacterium adhered were put into the centrifugal tubes, one for each, and allowed to act at 25 ⁇ 2° C. for 20 minutes. Thereafter, the carriers were transferred into centrifugal tubes containing 10 mL of an inactivator SCDLP medium (Eiken Chemical Co., Ltd.) , one for each, so as to inactivate the bactericidal component in the test liquid adhering to the carrier. The carriers were then treated with a sonicator at 20 ⁇ 2° C.
  • SCDLP medium Eiken Chemical Co., Ltd.
  • test liquids were agitated for an additional minute with a vortex mixer to prepare sample liquids for cell count and the number of surviving cells was counted.
  • a control was prepared by the same procedure as described above, except that the test liquids were replaced by sterile physiological saline.
  • sample liquids for cell count were serially diluted 10-fold with sterile physiological saline; the sample liquids or the series of dilutions, each weighing a volume of 1 mL, were transferred aseptically into Petri dishes and, after mixing with 20 mL of a TSA medium, they were solidified and cultured at 36 ⁇ 1° C. for 48 hours. Thereafter, colonies growing on the medium were counted to determine the number of surviving cells per carrier (lower limit for quantification: 10 CFU/carrier).
  • the control had a surviving cell count of 4.9.
  • the povidone iodine conditioned with purified water had a value of 3.9 whereas the povidone iodine conditioned with the water containing oxygen-filled ultrafine bubbles had a value of 1.4; an obvious difference was recognized between the bactericidal efficacies of the two.
  • Povidone particle particle Total particle iodine Sample Conditioning diameter density density concentration Cell count CFU/carrier description Water (nm) (10 8 particles/ml) (10 10 particles/ml) (mg/L) n1 n2 n3 average Log value Control — — — — — — 68000 110000 62000 80000 4.9 (physiological saline) Povidone water — — — 100 23000 19000 26000 8000 3.9 iodine water 91 3.1 2.3 100 10 10 50 23 1.4 containing oxygen-filled ultrafine bubbles
  • a grapefruit seed extract as a natural antibacterial agent was diluted with the water containing ultrafine bubbles or purified water so that it was conditioned to 0.5%.
  • a sterile conical flask was charged with about 5 mL of a 1 ⁇ 2 nutrient medium acclimatized to a test temperature (25 ⁇ 1° C.) and a suitable quantity of sterilized glass beads; thereafter, a platinum loop of cells of an incubated test bacterium was added. The contents of the flask were agitated with a test tube agitator. Subsequently, about 1 mL of the contents were transferred into a sterilized test tube and, after adding a suitable amount of a 1 ⁇ 2 nutrient medium, the contents were agitated with the test tube agitator such that the viable cell count was adjusted to be within the range of 2.5 ⁇ 10 8 to 12.5 ⁇ 10 8 cfu/ml.
  • a substance serving as a model contamination bovine serum albumin in aqueous solution; 30 g/L was added and mixed; the resulting mixture was left to stand for 2 minutes to prepare a test bacterial liquid.
  • a stainless steel disk was prepared as described in the Test for Bacteria Eradiating Activity of Residential Synthetic Detergents and Soaps; 0.01 mL of the test bacterial liquid, after being agitated again, was metered onto the disk and spread uniformly on a surface of the test piece.
  • the disk (test piece) was lidded with a Petri dish and allowed to stand at 25 ⁇ 1° C. until the test bacterial liquid became apparently dry. Thereafter, 0.1 mL of the test liquid was metered and spread uniformly onto a surface of the disk.
  • the disk was lidded with the Petri dish and allowed to stand at 25 ⁇ 1° C. for a minute. Thereafter, inactivation was conducted as instructed and the viable cells were counted.
  • the natural antibacterial agent conditioned with water had a viable cell count of 4.9 whereas the natural antibacterial agent conditioned with the water containing ultrafine bubbles had a value of 2.5; an obvious difference was recognized between the bactericidal efficacies of the two.
  • Streptococcus mutans (ATCC25175) was grown in a Tryptic soy Broth supplemented with 0.5% yeast extract (the resulting medium is hereinafter referred to as TSBY medium) at 37° C. until the OD 660 was between 0.6 and 0.8 (10 8 cells/mL); the product was used as a test bacterial liquid.
  • a TSBY medium (plus 1% sucrose) placed in a test tube in a volume of 4950 ⁇ L was inoculated with 50 ⁇ L of the test bacterial liquid and was cultured at 37° C. for 18 hours to form a biofilm.
  • the culture broth was removed by means of an aspirator and the biofilm was washed with 5 mL of an added PBS. After removing the PBS, 5 mL of the test liquid was treated for reaction as it was shaken with a shaking machine (37° C. ⁇ 20 min). After the 20-min reaction, 5 mL of 0.4% (w/v) sodium thiosulfate in solution was added into the test tube so as to inactivate the bactericidal agent. Using a sonicator, the biofilm was detached from the inner surfaces of the test tube and dispersed with a vortex mixer thereby prepare a sample liquid for cell count; the number of surviving cells in the biofilm was then counted.
  • sample liquids for cell count were diluted with a buffer solution; after culture in an MS agar medium (37° C. ⁇ 36-48 hours), the number of colonies formed was counted to determine the number of surviving cells in the biofilms.
  • the povidone iodine samples that had been conditioned with the purified water had cell counts in biofilms that were equivalent to 616.6 cfu and 9.2 cfu, whereas the povidone iodine samples conditioned with the water containing ultrafine bubbles had corresponding values of 149.2 cfu and 0 cfu; an obvious difference was recognized between the bactericidal efficacies of the two.
  • Povidone particle particle density (10 9 iodine Sample Conditioning diameter density particles/ concentration Cell count CFU description Water (nm) (10 7 particles/ml) ml) (mg/L) n1 n2 n3 n4 n5 average Povidone water — — — 1 612 439 1050 386 596 616.6 iodine water 100 2.0 1.6 250 35 178 150 133 149.2 containing oxygen-filled ultrafine bubbles water — — — 10 9 22 13 0 2 9.2 water 100 2.0 1.6 0 0 0 0 0 0 0 containing oxygen-filled ultrafine bubbles
  • Povidone particle particle Total particle iodine Sample Conditioning diameter density density concentration Cell count CFU/carrier description Water (nm) (10 8 particles/ml) (10 10 particles/ml) (mg/L) n1 n2 n3 average Log value Control — — — — — — 22000 34000 41999 32000 4.5 (physiological saline) Povidone water — — — 100 3200 1800 8600 4500 3.7 iodine water 75 5.7 4.6 10 75 ⁇ 10 32 1.5 containing atmospheric air-filled ultrafine bubbles water 76 2.7 1.3 ⁇ 10 ⁇ 10 ⁇ 10 ⁇ 10 1.0 containing C 3 F 8 filled ultrafine bubbles

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US10556256B2 (en) * 2014-05-28 2020-02-11 Takeda Pharmaceutical Company Limited Antibacterial water
WO2018003087A1 (ja) * 2016-06-30 2018-01-04 マルハニチロ株式会社 塩素系殺菌剤と微細気泡を組み合わせた殺菌剤、及び殺菌方法
JPWO2018003087A1 (ja) * 2016-06-30 2019-04-18 マルハニチロ株式会社 塩素系殺菌剤と微細気泡を組み合わせた殺菌剤、及び殺菌方法
US20200390919A1 (en) * 2017-11-29 2020-12-17 Freekira Pharmaceutical Inc. Antimicrobial agent containing hypochlorous acid
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