WO2006085975A2 - Organic biocidal decontamination compositions - Google Patents

Organic biocidal decontamination compositions Download PDF

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Publication number
WO2006085975A2
WO2006085975A2 PCT/US2005/023823 US2005023823W WO2006085975A2 WO 2006085975 A2 WO2006085975 A2 WO 2006085975A2 US 2005023823 W US2005023823 W US 2005023823W WO 2006085975 A2 WO2006085975 A2 WO 2006085975A2
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WO
WIPO (PCT)
Prior art keywords
composition
carrier
weight
biocide
silver
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Application number
PCT/US2005/023823
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French (fr)
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WO2006085975A3 (en
Inventor
Kyle Knappenberger
Lisa Martin
Paul S. Malchesky
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Nanoscale Materials, Inc.
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Application filed by Nanoscale Materials, Inc. filed Critical Nanoscale Materials, Inc.
Priority to EP05857504A priority Critical patent/EP1768680A2/en
Priority to JP2007519540A priority patent/JP2008505123A/en
Publication of WO2006085975A2 publication Critical patent/WO2006085975A2/en
Publication of WO2006085975A3 publication Critical patent/WO2006085975A3/en

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Classifications

    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01NPRESERVATION 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
    • A01N43/00Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/48Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
    • A01N43/541,3-Diazines; Hydrogenated 1,3-diazines
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01NPRESERVATION 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
    • A01N31/00Biocides, pest repellants or attractants, or plant growth regulators containing organic oxygen or sulfur compounds
    • A01N31/04Oxygen or sulfur attached to an aliphatic side-chain of a carbocyclic ring system
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01NPRESERVATION 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
    • A01N37/00Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids
    • A01N37/16Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids containing the group; Thio analogues thereof
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01NPRESERVATION 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
    • A01N59/00Biocides, pest repellants or attractants, or plant growth regulators containing elements or inorganic compounds
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01NPRESERVATION 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
    • A01N59/00Biocides, pest repellants or attractants, or plant growth regulators containing elements or inorganic compounds
    • A01N59/16Heavy metals; Compounds thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/13Amines
    • A61K31/14Quaternary ammonium compounds, e.g. edrophonium, choline
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00Medicinal preparations containing inorganic active ingredients
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00Medicinal preparations containing inorganic active ingredients
    • A61K33/04Sulfur, selenium or tellurium; Compounds thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00Medicinal preparations containing inorganic active ingredients
    • A61K33/22Boron compounds
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00Medicinal preparations containing inorganic active ingredients
    • A61K33/40Peroxides
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca

Definitions

  • the present invention is broadly concerned with decontamination compositions and methods useful for the neutralization or destruction of biological agents such as biological weapon (BW) agents and environmentally-derived undesirable biological agents (e.g., spores, bacteria, viruses, fungi, and molds). More particularly, the invention is concerned with such compositions and methods which may be in liquid form as sprayable or foamable products for example, and which include a biocide fraction together with a carrier; the compositions preferably are organic in character and have only minimal quantities of water.
  • biological weapon BW
  • environmentally-derived undesirable biological agents e.g., spores, bacteria, viruses, fungi, and molds.
  • Patent No. 5 ,914,436 describes methods for the destruction of unwanted compounds such as chlorocarbons, chlorofluorocarbons and PCBs, making use of metal oxide composites as adsorbents.
  • Patent No. 6,057,488 describes the use of metal oxide nanoparticles for the destructive adsorption of biological and chemical contaminants, including biological and chemical warfare agents and environmental contaminants.
  • Sandia National Laboratories has recently developed a foam decontamination product referred to as "Sandia Decon Formulation” and includes solubilizing compounds such as cationic surfactants and hydrotropes together with reactive compound(s) such as nucleophilic and oxidizing compounds.
  • the Sandia foam products are available from EnviroFoam Technologies of Huntsville, Alabama, and Modec, Inc. of Denver, Colorado, and are described in PCT Publication WO 02/02192 published January 10, 2002 and incorporated by reference herein.
  • the present invention is concerned with decontamination compositions having a relatively low water content (less than about 10% by weight water, more preferably less than about 2% by weight and still more preferably less than about 0.1% by weight water) and including a biocide fraction together with a carrier.
  • the carrier includes a component different than any component of the biocide fraction and is broadly selected from the group consisting of straight or branched chain substituted or unsubstituted halogen C3-C15 hydrocarbons, Cl -C 12 straight or branched chain alkyl alcohols, and mixtures thereof.
  • the compositions of the invention are useful for the neutralization or destruction of biological agents including biological warfare agents and environmental contaminants.
  • the products of the invention may be in the form of liquid sprayable products or can be used in the form of fogs, mists, vapors, gels, pastes, or wipes.
  • a "wipe” is a sheet of woven or unwoven material, formed of natural or synthetic fibers, onto which a quantity of the inventive composition is absorbed.
  • the biocide fraction is preferably selected from the group consisting of biocidally effective organic peroxides, oxides, aldehydes, phenols, napthas and acids, quaternary ammonium compounds, transition metals and salts thereof, the halogens, compounds containing a halogen, N, S or B atom, ozone and mixtures thereof.
  • preferred biocides are selected from the group consisting of organic peroxides, formaldehyde, glutaraldehyde, peroxyacetic acid, ozone, the alkali metal chlorites and hypochlorites (e.g., sodium or potassium chlorite and hypochlorite), chlorine, chlorine dioxide, alkylene oxides (e.g., ethylene and propylene oxides), 2-amino-2-methyl-l-propanol, cetyltrimethylammonium bromide, cetylpyridinium chloride, 2,4,4-trichloro-2-hydroxydiphenylether, l-(4-chlorophenyl)-3-(3,4- dichlorophenyl) urea, zinc salts, pentachlorophenol, copper naphthenate, tributyltin oxide, dichlorophen, p-nitrophenol, p-chloro-m-xylenol, beta-naphthol, 2,3,5,6-te
  • Known antimicrobial compounds can be used in the compositions such as hydrogen peroxide 0.8% in combination with peroxyacetic acid 0.06%; sodium chlorite 1.52%; amylphenol 7.6%; ethylene oxide 8.5%; sodium hypochlorite 12.5%; sodium chlorite 72.8%; hydrogen peroxide 6.9% in combination with peroxyacetic acid 4.4% and octanoic acid 3.3%; hydrogen peroxide 22% in combination with 4.5% peroxyacetic acid 4.5%; peroxyacetic acid 35%; and hydrogen peroxide 31%.
  • the biocide fraction is present in the overall composition at a level of from about 0.01- 10% by weight, more preferably from about 1-5% by weight.
  • the most preferred class of carriers are the substituted fluorinated C3-C15 hydrocarbons, and especially alkoxy-substituted hydrocarbons of this class.
  • exemplary carriers are the HFE solvents such as HFE 7100 (methoxynonafluorobutane), 71DA (HFE7100, trans- 1,2- dichloroethylene and ethanol azeotrope), 7 HPA (HFE7100 and ethanol azeotrope), and 7500 (2- trifluoromethyl-3-ethoxydodecofluorohexane), and mixtures thereof.
  • HFE solvents such as HFE 7100 (methoxynonafluorobutane), 71DA (HFE7100, trans- 1,2- dichloroethylene and ethanol azeotrope), 7 HPA (HFE7100 and ethanol azeotrope), and 7500 (2- trifluoromethyl-3-ethoxydodecofluorohexane), and mixtures thereof.
  • a carrier in the form of a mixture of one or more of the fluorinated hydrocarbons described above together with a C 1 - C6 alkyl alcohol such as ethanol.
  • the alcohol should be present at a level up to about 20% by weight and more preferably less than about 5% by weight.
  • Particularly effective sporicides have been prepared using this type of combined fluorinated hydrocarbon/alkyl alcohol carrier with a silver salt as a biocide, e.g., silver nitrate or with hydrogen peroxide, peroxyacetic acid, or hypochlorite.
  • compositions of the invention may also be advisable to include a surfactant in the compositions of the invention to increase the dispersibility of the biocide in the carrier.
  • a surfactant in the compositions of the invention to increase the dispersibility of the biocide in the carrier.
  • a large number of surfactants would be suitable, depending upon desired end uses.
  • cationic, anionic, nonionic or amphoteric surfactants may be used in the compositions.
  • the surfactant when used is normally present at a level of from about 0.1 to 20% by weight of the composition, and more preferably less than about 3% by weight.
  • compositions of the invention may be used for decontaminating an area by distributing the compositions into or adjacent the area. That is, the compositions may be used to decontaminate surfaces such as buildings, walls, or other structures, equipment, furniture, and the soil. Additionally, the compositions can be used for decontaminating contaminated ambient atmosphere by distribution in the form of a fog, mist, vapor or spray, or may be incorporated into gels, pastes, and wipes for decontaminating inanimate or animate objects. A variety of application equipment and techniques can be used in this context, for example equipment for pressurized broadcast applications, or for layering onto surfaces. Depending upon the biocide fraction selected, the compositions may be used for the neutralization or destruction of bacterial spores, vegetative bacteria, viruses, fungi and molds, or any other bacteriological or infectious agent.
  • the area or surface to be decontaminated may be incompatible with the biocide compositions used with the present invention.
  • the carrier composition (without the biocide) may be used to collect and remove the biological agent from the area.
  • the biological agent may then be deactivated by adding the biocide to the carrier containing the biological agent.
  • a series of formulations were evaluated by placement in a glass screening vial.
  • 5 ml of distilled water was added to a separate screening vial.
  • a concentration of either 10 5 CFU/100 ⁇ l or 1.5 x 10 7 CFU/100 ⁇ l of bacterial spores ⁇ Bacillus subtilus) was added to each vial for a concentration of approximately 3 x 10 6 CFU/ml (for the higher challenges).
  • the vials were capped and vortexed for 30 seconds, whereupon they were allowed to sit undisturbed for 74.5 minutes. After the 74.5 minute sit time had elapsed, each vial was again vortexed for 30 seconds.
  • the suspensions were then filtered by placing a membrane filter on a filtering apparatus and adding 50 ml of distilled water to each filter followed by 100 ⁇ l of solution from a screening vial (appropriate dilutions were carried out on the higher concentration challenges) . After the initial filtering, the filters were washed twice with 25 ml of distilled water. Once the liquid was removed, the filters were taken from the apparatus and placed on a nutrient agar plate and incubated 24 hours at 37 0 C. All experiments were sampled in triplicate at room temperature.
  • HFE solvents formulations 1 and 2
  • silver compounds Formulations 3-7
  • dichumyl peroxide Formulations 8-10
  • sodium hypochlorite/bleach Formulations 11-18
  • peroxyacetic acid Formulations 19-24
  • hydrogen peroxide Formulamulations 25-26.
  • Different carriers were used in respective formulations, as set forth in Table 1.
  • Example 2 In this test, the surface decontamination properties of certain compositions in accordance with the invention were tested. Initially, 1 inch square glass sides were inoculated with 100 ⁇ l of an approximately 1.5 x 10 8 CFU/ml solution of Bacillus subtilus spores in 40% ethanol, and allowed to dry for 2-3 hours. The biocidal formulations being evaluated were prepared minutes before use. The glass slides were each placed in a small plastic jar with a volume of about 30 ml. Each test slide receiving biocide was sprayed with 2.27 ml of the test formulation. Another slide served as a dry control (no formulation added) while a third slide was sprayed with 2.27 ml distilled water (wet control).
  • AU slides were left in the jars, uncapped for 75 minutes. Once the 75 minutes elapsed, 20 ml of distilled water was added to each jar whereupon the jars were capped, vortexed for 30 seconds, and left undisturbed for 10 minutes to elute the spores. Once the 10 minutes had elapsed, the jars were vortexed for a few seconds and 100 ⁇ l of solution removed and diluted in 1.9 ml of distilled water. The diluted mixtures were then filtered by placing a membrane filter on the filtering apparatus and adding 50 ml of distilled water to each filter followed by 100 ⁇ l of test solution (25 ⁇ l for the controls).
  • the filters were washed twice with 25 ml of distilled water. After removing all liquid, the filters were taken from the apparatus and placed on a nutrient agar plate and incubated 24 hours at 37 0 C. All experiments were conducted in triplicate at room temperature.
  • test solutions included HFE-7100 and HFE-7500 solvent supplemented with 13% by weight ethanol and with 0.22% by weight silver nitrate added. These test formulations were prepared by initially dispersing the silver nitrate in ethanol, followed by addition thereof to the HFE solvent. These steps were carried at room temperature with appropriate mixing of the formulation prior to adding it to the cultures. The following table sets forth the results of this test.
  • the spore suspension of the stock specimen was grown on potato dextrose agar (PDA) for approximately one month for the mycelial cultures and on corn meal agar (CMA) for five weeks for the spore cultures, all at room temperature in the dark side of a fume hood.
  • PDA potato dextrose agar
  • CMA corn meal agar
  • the petri dishes were sealed with parafilm.
  • the plates were used to test the effectiveness of the formulations against the mycelial form (PDA) and spore form (CMA). Five ml of each of the formulations were sprayed to evenly cover the entire surface area of the plate in a Biosafety cabinet with vertical flow.
  • PDA mycelial form
  • CMA spore form
  • the formulation was in contact with the specimen for 75 minutes. After the contact time, each treated and control plate had six plugs removed therefrom and transferred to a new PDA plate. The plates were incubated for approximately 1 -2 weeks at room temperature in the dark in a fume hood. The regrowth for each plug was visually determined as emerging mycelium. Untreated controls were used as a gauge of when sufficient growth was achieved. All experiments were sampled in triplicate.
  • Each PDA plate was qualitatively evaluated for the number of plugs that resulted in regrowth on a scale of 0 to 6, with "0" indicating a low level of activity, and "6" indicating a high level of activity.
  • the plates were scored as a number of positive regrowths, the number of kills, and the number of inhibitions.
  • the positive control and distilled water were used to determine the baseline regrowth and for comparison to determine growth inhibition.
  • the sterile distilled water, carrier solvent, and the potato flour treatments were evaluated to determine if the conditions of treatment resulted in reduced growth. All resulted in full regrowth.
  • the results are given in Table 3.
  • the CMA plates were treated in the same manner as the PDA plates for the Stachybotrys mycelia test.
  • the formulation was sprayed evenly on the agar plate in a Biosafety cabinet with vertical flow (Class II) and sealed with parafilm for 75 minutes. Once the 75 minutes had elapsed, 10 ml of sterile deionized water with 0.1% Tween 80 was added to the CMA plate and gently stirred. 150 ⁇ l of the recovered sterile distilled water containing sporces was plated onto PDA in triplicate. The plates were incubated 1-2 weeks at room temperature in a fume hood and the number of established colonies counted. The results are given in Table 4.

Abstract

Organic decontamination compositions and methods of use thereof are provided which include a biocide fraction dispersed in a substantially non-aqueous carrier and having less than about 10% by weight water. The biocide fraction is preferably consisting of biocidally effective organic peroxides, oxides, aldehydes, phenols, napthas and acids, quaternary ammonium compounds, transition metal salts, the halogens, compounds containing a halogen, N, S or B atom, ozone and mixtures thereof. The carrier advantageously includes a component different than the biocide fraction and selected from the group consisting of straight or branched chain, substituted or unsubstituted halogenated C3-C15 hydrocarbons, CI-C12 straight or branched chain alkyl alcohols, and mixtures thereof.

Description

ORGANIC BIOCIDAL DECONTAMINATION COMPOSITIONS
BACKGROUND OF THE INVENTION
Field of the Invention
The present invention is broadly concerned with decontamination compositions and methods useful for the neutralization or destruction of biological agents such as biological weapon (BW) agents and environmentally-derived undesirable biological agents (e.g., spores, bacteria, viruses, fungi, and molds). More particularly, the invention is concerned with such compositions and methods which may be in liquid form as sprayable or foamable products for example, and which include a biocide fraction together with a carrier; the compositions preferably are organic in character and have only minimal quantities of water.
Description of the Prior Art
Governments around the world have become increasingly concerned about the effects of biological warfare agents and other types of hazardous substances, particularly in light of the recent rise in terrorism. The potentially catastrophic results which could ensue in high density population centers subjected to such agents are well known to disaster experts. In addition, concerns over environmental biological contaminants raise concerns over public safety. In particular, concerns and issues of biological contamination of buildings by molds or fungi following flooding or water damage raise concerns to the health of individuals working or living therein.
There are currently two general types of decontamination methods for biological agents, namely chemical disinfection and physical decontamination. Chemical disinfectants such as hypochlorite solutions are useful but are corrosive to most metals and fabrics, and to human skin. Liquid-like foam disinfectants have also been used, and generally require water and pressurized gases for efficient application. Further, gaseous disinfectants such as ozone, hydrogen peroxide, or chlorine dioxide may also be used but require containment means usually in their use and are prone to inactivation by building construction materials and contents. Physical decontamination usually involves dry heat up to 16O0C for 2 hours or steam or super-heated steam for about 20 minutes. Sometimes UV light can be used effectively, but it is generally difficult to implement in actual practice and is ineffective when shadowing occurs.
U.S. Patent No . 5 ,914,436 describes methods for the destruction of unwanted compounds such as chlorocarbons, chlorofluorocarbons and PCBs, making use of metal oxide composites as adsorbents. Also, Patent No. 6,057,488 describes the use of metal oxide nanoparticles for the destructive adsorption of biological and chemical contaminants, including biological and chemical warfare agents and environmental contaminants.
Sandia National Laboratories has recently developed a foam decontamination product referred to as "Sandia Decon Formulation" and includes solubilizing compounds such as cationic surfactants and hydrotropes together with reactive compound(s) such as nucleophilic and oxidizing compounds. The Sandia foam products are available from EnviroFoam Technologies of Huntsville, Alabama, and Modec, Inc. of Denver, Colorado, and are described in PCT Publication WO 02/02192 published January 10, 2002 and incorporated by reference herein.
SUMMARY OF THE INVENTION
The present invention is concerned with decontamination compositions having a relatively low water content (less than about 10% by weight water, more preferably less than about 2% by weight and still more preferably less than about 0.1% by weight water) and including a biocide fraction together with a carrier. The carrier includes a component different than any component of the biocide fraction and is broadly selected from the group consisting of straight or branched chain substituted or unsubstituted halogen C3-C15 hydrocarbons, Cl -C 12 straight or branched chain alkyl alcohols, and mixtures thereof. The compositions of the invention are useful for the neutralization or destruction of biological agents including biological warfare agents and environmental contaminants. The products of the invention may be in the form of liquid sprayable products or can be used in the form of fogs, mists, vapors, gels, pastes, or wipes. As used herein, a "wipe" is a sheet of woven or unwoven material, formed of natural or synthetic fibers, onto which a quantity of the inventive composition is absorbed.
The biocide fraction is preferably selected from the group consisting of biocidally effective organic peroxides, oxides, aldehydes, phenols, napthas and acids, quaternary ammonium compounds, transition metals and salts thereof, the halogens, compounds containing a halogen, N, S or B atom, ozone and mixtures thereof. More particularly, preferred biocides are selected from the group consisting of organic peroxides, formaldehyde, glutaraldehyde, peroxyacetic acid, ozone, the alkali metal chlorites and hypochlorites (e.g., sodium or potassium chlorite and hypochlorite), chlorine, chlorine dioxide, alkylene oxides (e.g., ethylene and propylene oxides), 2-amino-2-methyl-l-propanol, cetyltrimethylammonium bromide, cetylpyridinium chloride, 2,4,4-trichloro-2-hydroxydiphenylether, l-(4-chlorophenyl)-3-(3,4- dichlorophenyl) urea, zinc salts, pentachlorophenol, copper naphthenate, tributyltin oxide, dichlorophen, p-nitrophenol, p-chloro-m-xylenol, beta-naphthol, 2,3,5,6-tetrachloro-4-(methyl sulfonyl)-pyridine, salicylanilide, bromoacetic acid, alkyl quaternary ammonium acetate, sodium ethyl mercuric thiosalicylate, sodium orthophenyl phenate, n-alkyl (C12 to C18) dimethyl benzyl ammonium chloride, organoborates, 2,2-(l-methyltrimethylenedioxy)-bis-(4-methyl- 1,3,2- dioxaborinane), 2,2-oxybis(4,4,6-trimethyl)-l,3,2-dioxaborinane, ethylene glycol monomethyl ether, parahydroxy benzoates, organic boron compounds, 8-hydroxyquinoline, sodium pentachlorophenate, dimethylethylalkylbenzyl ammonium chloride, alkylammonium salts of 2- pyridinethiol-1 -oxide, l,3,5-triethylhexahydro-l,3,5-triazine, strontium chromate, halogenated phenols (e.g., 2-bromo-4-phenylphenol), silver, silver salts (e.g., silver nitrate, silver chloride, silver oxide), silver sulfadiazine, elemental copper, copper salts (copper nitrate, copper sulfate, copper oxide) sodium dichloro-s-triazinetrione, substituted paraffins (e.g., 3-chloro-3-nitro-2- butanol, 2-chloro-2-nitro-l-butanol stearate, 2-chloro-2-nitrobutyl acetate, 4-chloro-4-nitro-3- hexanol, 1-chloro-l-nitro-l-propanol, 2-chloro-2-nitro-l-propanol), triethyltin chloride, 2,4,5- trichlorophenol, 2,4,6-trichlorophenol, 2,2-thiobis(3,4,6- trichlorophenol), l,3-dichloro-5,5- dimethylhydantoin, tris(hydoxy-methyl)nitromethane, nitroparaffins, hexahydro-l,3,5-tris(2- hydroxy-ethyl)-s-triazine, 1 ,3 ,5-tris(tetrahydro-2-furanyl)-methyl-hexahydro-s-triazine, methyl bisthiocyanate, 2,2-dibromo-3-nitrilopropionamide, β-bromo-β-nitrostyrene, fluorinated compounds (e.g., N-ethyl-N-methyl-4-(trifluoromethyl)-2-(3,4-dimethoxyphenyl) benzamide), pentachlorophenol, dichlorophene, orthophenyl phenol, di-bicyclo-(3 , 1 , 1 or 2,2, 1 )-heptyl and di- bicyclo-(3,l,l or 2,2,l)-heptenyl polyamines, and mixtures thereof. Known antimicrobial compounds can be used in the compositions such as hydrogen peroxide 0.8% in combination with peroxyacetic acid 0.06%; sodium chlorite 1.52%; amylphenol 7.6%; ethylene oxide 8.5%; sodium hypochlorite 12.5%; sodium chlorite 72.8%; hydrogen peroxide 6.9% in combination with peroxyacetic acid 4.4% and octanoic acid 3.3%; hydrogen peroxide 22% in combination with 4.5% peroxyacetic acid 4.5%; peroxyacetic acid 35%; and hydrogen peroxide 31%. Preferably, the biocide fraction is present in the overall composition at a level of from about 0.01- 10% by weight, more preferably from about 1-5% by weight.
The most preferred class of carriers are the substituted fluorinated C3-C15 hydrocarbons, and especially alkoxy-substituted hydrocarbons of this class. Exemplary carriers are the HFE solvents such as HFE 7100 (methoxynonafluorobutane), 71DA (HFE7100, trans- 1,2- dichloroethylene and ethanol azeotrope), 7 HPA (HFE7100 and ethanol azeotrope), and 7500 (2- trifluoromethyl-3-ethoxydodecofluorohexane), and mixtures thereof. It is preferred that the fluorinated hydrocarbons be highly fluorinated, and more preferably at all of the hydrocarbon chain substitution sites thereof. Good results are also obtained by preparing a carrier in the form of a mixture of one or more of the fluorinated hydrocarbons described above together with a C 1 - C6 alkyl alcohol such as ethanol. In such combinations, the alcohol should be present at a level up to about 20% by weight and more preferably less than about 5% by weight. Particularly effective sporicides have been prepared using this type of combined fluorinated hydrocarbon/alkyl alcohol carrier with a silver salt as a biocide, e.g., silver nitrate or with hydrogen peroxide, peroxyacetic acid, or hypochlorite.
In some instances, it may also be advisable to include a surfactant in the compositions of the invention to increase the dispersibility of the biocide in the carrier. A large number of surfactants would be suitable, depending upon desired end uses. Thus, cationic, anionic, nonionic or amphoteric surfactants may be used in the compositions. The surfactant when used is normally present at a level of from about 0.1 to 20% by weight of the composition, and more preferably less than about 3% by weight.
The compositions of the invention may be used for decontaminating an area by distributing the compositions into or adjacent the area. That is, the compositions may be used to decontaminate surfaces such as buildings, walls, or other structures, equipment, furniture, and the soil. Additionally, the compositions can be used for decontaminating contaminated ambient atmosphere by distribution in the form of a fog, mist, vapor or spray, or may be incorporated into gels, pastes, and wipes for decontaminating inanimate or animate objects. A variety of application equipment and techniques can be used in this context, for example equipment for pressurized broadcast applications, or for layering onto surfaces. Depending upon the biocide fraction selected, the compositions may be used for the neutralization or destruction of bacterial spores, vegetative bacteria, viruses, fungi and molds, or any other bacteriological or infectious agent.
In some instances, the area or surface to be decontaminated may be incompatible with the biocide compositions used with the present invention. In such case, the carrier composition (without the biocide) may be used to collect and remove the biological agent from the area.
Next, the biological agent may then be deactivated by adding the biocide to the carrier containing the biological agent.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT The following examples set forth preferred decontamination compositions, as well as methods of formulation and use thereof. It is to be understood, however, that these examples are provided by way of illustration and nothing therein should be taken as a limitation upon the overall scope of the invention.
Example 1
In this test, a series of formulations (each 5 ml total volume) were evaluated by placement in a glass screening vial. As a control, 5 ml of distilled water was added to a separate screening vial. A concentration of either 105 CFU/100 μl or 1.5 x 107 CFU/100 μl of bacterial spores {Bacillus subtilus) was added to each vial for a concentration of approximately 3 x 106 CFU/ml (for the higher challenges). The vials were capped and vortexed for 30 seconds, whereupon they were allowed to sit undisturbed for 74.5 minutes. After the 74.5 minute sit time had elapsed, each vial was again vortexed for 30 seconds. The suspensions were then filtered by placing a membrane filter on a filtering apparatus and adding 50 ml of distilled water to each filter followed by 100 μl of solution from a screening vial (appropriate dilutions were carried out on the higher concentration challenges) . After the initial filtering, the filters were washed twice with 25 ml of distilled water. Once the liquid was removed, the filters were taken from the apparatus and placed on a nutrient agar plate and incubated 24 hours at 370C. All experiments were sampled in triplicate at room temperature.
The potential biocides used in this experiment were: HFE solvents (Formulations 1 and 2); silver compounds (Formulations 3-7); dichumyl peroxide (Formulations 8-10); sodium hypochlorite/bleach (Formulations 11-18); peroxyacetic acid (Formulations 19-24); and hydrogen peroxide (Formulations 25-26). Different carriers were used in respective formulations, as set forth in Table 1.
Table 1 Effect of Biocides on Bacillus subtilus Spores
Figure imgf000007_0001
Figure imgf000008_0001
As expected, the use of preferred carrier materials (HFE solvents) alone gave very little sporicidal activity (Formulations 1 and 2). The silver salts were shown to be effective sporacides, when used in conjunction with the HFE carriers and especially with a carrier made up of ethanol and HFE solvent. When water was used in lieu of an HFE solvent (Formulation 7), only two log reduction was observed, suggesting a synergistic effect when the ethanol and HFE solvent combination was employed (Formulations 3-6).
Good results were observed when using the organic peroxide and sodium hypochlorite or commercial household bleach (6% hypochlorite content) (Formulations 8-18). Peroxyacetic acid when added to HFE-7500 (1.25% by weight of the total mass) or HFE-7100 (0.64% by weight of the total mass) was able to achieve greater than six log reduction (Formulations 19, 21, and 23). Likewise these HFE solvents containing hydrogen peroxide (1.25% by weight of the total mass) achieve 6.6 log reduction (Formulations 25-26).
Example 2 In this test, the surface decontamination properties of certain compositions in accordance with the invention were tested. Initially, 1 inch square glass sides were inoculated with 100 μl of an approximately 1.5 x 108 CFU/ml solution of Bacillus subtilus spores in 40% ethanol, and allowed to dry for 2-3 hours. The biocidal formulations being evaluated were prepared minutes before use. The glass slides were each placed in a small plastic jar with a volume of about 30 ml. Each test slide receiving biocide was sprayed with 2.27 ml of the test formulation. Another slide served as a dry control (no formulation added) while a third slide was sprayed with 2.27 ml distilled water (wet control). AU slides were left in the jars, uncapped for 75 minutes. Once the 75 minutes elapsed, 20 ml of distilled water was added to each jar whereupon the jars were capped, vortexed for 30 seconds, and left undisturbed for 10 minutes to elute the spores. Once the 10 minutes had elapsed, the jars were vortexed for a few seconds and 100 μl of solution removed and diluted in 1.9 ml of distilled water. The diluted mixtures were then filtered by placing a membrane filter on the filtering apparatus and adding 50 ml of distilled water to each filter followed by 100 μl of test solution (25 μl for the controls). After the initial filtering, the filters were washed twice with 25 ml of distilled water. After removing all liquid, the filters were taken from the apparatus and placed on a nutrient agar plate and incubated 24 hours at 370C. All experiments were conducted in triplicate at room temperature.
The test solutions included HFE-7100 and HFE-7500 solvent supplemented with 13% by weight ethanol and with 0.22% by weight silver nitrate added. These test formulations were prepared by initially dispersing the silver nitrate in ethanol, followed by addition thereof to the HFE solvent. These steps were carried at room temperature with appropriate mixing of the formulation prior to adding it to the cultures. The following table sets forth the results of this test.
Table 2 Surface Decontamination of Bacillus Subtilis Spores Using AgNO3 In HFE/Ethanol Carrier
Figure imgf000009_0001
The foregoing results confirm that the silver nitrate in ethanol when added to either type of HFE solvent results in high log reduction and surface decontamination. Formulation #30 using silver nitrate/ethanol/HFE-7500 had only one colony present in three samplings suggesting that this formulation is also very effective.
Example 3
In this example, the fungicidal properties of peroxyacetic acid dispersed in an HFE 7500 carrier (Formulation 21) on Stachybotrys species (ATCC#9182), purchased from the American Type Culture Collection, in the mycelial and spore forms were tested. The spore suspension of the stock specimen was grown on potato dextrose agar (PDA) for approximately one month for the mycelial cultures and on corn meal agar (CMA) for five weeks for the spore cultures, all at room temperature in the dark side of a fume hood. The petri dishes were sealed with parafilm.
After incubation, the plates were used to test the effectiveness of the formulations against the mycelial form (PDA) and spore form (CMA). Five ml of each of the formulations were sprayed to evenly cover the entire surface area of the plate in a Biosafety cabinet with vertical flow.
For the mycelium study, the formulation was in contact with the specimen for 75 minutes. After the contact time, each treated and control plate had six plugs removed therefrom and transferred to a new PDA plate. The plates were incubated for approximately 1 -2 weeks at room temperature in the dark in a fume hood. The regrowth for each plug was visually determined as emerging mycelium. Untreated controls were used as a gauge of when sufficient growth was achieved. All experiments were sampled in triplicate.
Each PDA plate was qualitatively evaluated for the number of plugs that resulted in regrowth on a scale of 0 to 6, with "0" indicating a low level of activity, and "6" indicating a high level of activity. The plates were scored as a number of positive regrowths, the number of kills, and the number of inhibitions. The positive control and distilled water were used to determine the baseline regrowth and for comparison to determine growth inhibition. The sterile distilled water, carrier solvent, and the potato flour treatments were evaluated to determine if the conditions of treatment resulted in reduced growth. All resulted in full regrowth. The negative control, full strength bleach, resulted in 0/6 regrowth and 6/6 kills. The results are given in Table 3.
Table 3 Decontamination of Stachybotrys mycelia usin HFE-7500 and peroxyacetic acid at 1 week.
Figure imgf000010_0001
In the decontamination study of the Stachybotrys spores, the CMA plates were treated in the same manner as the PDA plates for the Stachybotrys mycelia test. The formulation was sprayed evenly on the agar plate in a Biosafety cabinet with vertical flow (Class II) and sealed with parafilm for 75 minutes. Once the 75 minutes had elapsed, 10 ml of sterile deionized water with 0.1% Tween 80 was added to the CMA plate and gently stirred. 150 μl of the recovered sterile distilled water containing sporces was plated onto PDA in triplicate. The plates were incubated 1-2 weeks at room temperature in a fume hood and the number of established colonies counted. The results are given in Table 4.
Table 4
Decontamination of Stachybotys spores using HFE 7500 and peroxyacetic acid
Figure imgf000011_0001
The HFE 7500 combined with theperoxyacetic acid inhibited growth, showed kill, and inhibited growth for the mycelia study and showed complete kill in the spore study.

Claims

We claim:
1. A decontamination composition comprising a biocide fraction dispersed in a substantially non-aqueous carrier, said composition having less than about 10% by weight water, said carrier including a component different than said biocide fraction and selected from the group consisting of straight or branched chain, substituted or unsubstituted halogenated C3- Cl 5 hydrocarbons, Cl -C 12 straight or branched chain alkyl alcohols, and mixtures thereof.
2. The composition of claim 1 , said biocide fraction selected from the group consisting of biocidally effective organic peroxides, oxides, aldehydes, phenols, napthas and acids, quaternary ammonium compounds, transition metals and salts thereof, the halogens, compounds containing a halogen, N, S or B atom, ozone and mixtures thereof.
3. The composition of claim 2, said biocide selected from the group consisting of formaldehyde, glutaraldehyde, peroxyacetic acid, ozone, the alkali metal hypochlorites, chlorine, chlorine dioxide, alkylene oxides, 2-amino-2-methyl-l-propanol, cetyltrimethylammonium bromide, cetylpyridinium chloride, 2,4,4-trichloro-2- hydroxydiphenylether, l-(4-chlorophenyl)-3-(3s4-dichlorophenyl) urea, zinc salts, pentachlorophenol, copper naphthenate, tributyltin oxide, dichlorophen, p-nitrophenol, p-chloro- m-xylenol, beta-naphthol, 2,3,5,6-tetrachloro-4-(methyl sulfonyl)-pyridine, salicylanilide, bromoacetic acid, alkyl quaternary ammonium acetate, sodium ethyl mercuric thiosalicylate, sodium orthophenyl phenate, n-alkyl (C12 to C18) dimethyl benzyl ammonium chloride, organoborates, 2,2-(l-methyltrimethylenedioxy)-bis-(4-methyl-l,3,2- dioxaborinane), 2,2- oxybis(4,4,6-trimethyl)-l,3,2-dioxaborinane, ethylene glycol monomethyl ether, parahydroxy benzoates, organic boron compounds, 8-hydroxyquinoline, sodium pentachlorophenate, dimethylethylalkylbenzyl ammonium chloride, alkylammonium salts of 2-pyridinethiol- 1 -oxide, l,3,5-triethylhexahydro-l,3,5-triazine, strontium chromate, halogenated phenols, silver salts, silver oxide, silver, silver sulfadiazine, copper, copper salts, sodium dichloro-s-triazinetrione, substituted paraffins, triethyltin chloride, 2,4,5-trichlorophenol, 2,4,6-trichlorophenol, 2,2- thiobis(3,4,6- trichlorophenol), l,3-dichloro-5,5-dimethylhydantoin, tris(hydoxy- methyl)nitromethane, nitroparaffms, hexahydro-l,3,5-tris(2-hydroxy-ethyl)-s-triazine, 1,3,5- tris(tetrahydro-2-furanyl)-methyl-hexahydro-s-triazine, methyl bisthiocyanate, 2,2-dibromo-3- nitrilopropionamide, β-bromo-β-nitrostyrene, fluorinated compounds, pentachlorophenol, dichlorophene, orthophenyl phenol, di-bicyclo-(3,l,l or 2,2,l)-heptyl and di-bicyclo-(3,l,l or 2,2,l)-heptenyl polyamines, and mixtures thereof.
4. The composition of claim 1 , said composition having less than about 2% by weight water.
5. The composition of claim 1 , said composition having less than about 0.1% by weight water.
6. The composition of claim 1 , said biocide fraction being present at a level of from about 0.01-10% by weight in said composition.
7. The composition of claim 6, said level being from about 1 -5% by weight in said composition.
8. The composition of claim 1 , said carrier including a substituted fluorinated
C3-C15 hydrocarbon.
9. The composition of claim 8, said substituted C3 -C 15 hydrocarbon having fluorine atoms at all of the hydrocarbon chain substitutions sites thereof.
10. The composition of claim 8, said fluorinated C3-C15 hydrocarbon being alkoxy-substituted.
11. The composition of claim 10, said carrier selected from the group consisting of methoxynonafluorobutane and 2-trifluoromethyl-3-ethoxydodecofluorohexane.
12. The composition of claim 1, said carrier comprising a mixture of a Cl -C6 alkyl alcohol and a substituted fluorinated C3-C15 hydrocarbon.
13. The composition of claim 12, said C1-C6 alkyl alcohol being present at a level of up to about 20% by weight in said carrier.
14. The composition of claim 12, said level being less than about 5% by weight in said carrier.
15. The composition of claim 12, said substituted fluorinated C3-C15 hydrocarbon selected from the group consisting of methoxynonafluorobutane and 2- trifluoromethyl-3-ethoxydodecofluorohexane.
16. The composition of claim 15, said biocide comprising a silver salt.
17. The composition of claim 1 , including a surfactant.
18. The composition of claim 17, said surfactant selected from the group consisting of cationic, anionic, nonionic or amphoteric surfactants.
19. The composition of claim 17, said surfactant being present at a level of from about 0.1 to 20% by weight in said composition.
20. The composition of claim 17, said surfactant being present at a level of less than about 3% by weight in said composition.
21. A decontamination composition comprising silver or a silver salt dispersed in a substantially non-aqueous carrier, said composition having up to about 10% by weight water, said carrier comprising a mixture of a C1-C6 alkyl alcohol and a substituted fluorinated C3-C15 hydrocarbon.
22. The composition of claim 21, said C1-C6 alkyl alcohol being present at a level of up to about 20% by weight in said carrier.
23. The composition of claim 21, said level being less than about 5% by weight in said carrier.
24. The composition of claim 21, said substituted fluorinated C3-C15 hydrocarbon selected from the group consisting of methoxynonafluorobutane and 2- trifluoromethyl-3 -ethoxydodecofluorohexane .
25. The composition of claim 21 , said silver salt being silver nitrate.
26. The composition of claim 21 , including a surfactant.
27. The composition of claim 26, said surfactant selected from the group consisting of cationic, anionic, nonionic or amphoteric surfactants.
28. The composition of claim 27, said surfactant being present at a level of from about 0.1 to 20% by weight in said composition.
29. The composition of claim 27, said surfactant being present at a level of less than about 3% by weight in said composition.
30. A method of decontaminating an area comprising the step of distributing a composition according to claim 1 into or adjacent said area.
31. The method of claim 30, said composition being in the form of a liquid, said distributing step comprising the step of applying the composition as a spray, fog, mist, vapor or layer into or adjacent said area.
32. The method of claim 30, said composition being in the form of a gel or paste, said distributing step comprising the step of applying the composition as a layer into or adjacent said area.
33. The method of claim 30, said composition being absorbed onto a wipe, said distributing step comprising the step of applying the composition by contacting the wipe into or adjacent said area.
34. A method of decontaminating an area comprising the step of applying a composition according to claim 21 into or adjacent said area.
35. The method of claim 34, said composition being in the form of a liquid, said distributing step comprising the step of applying the composition as a spray, fog, mist, vapor or layer into or adjacent said area.
36. The method of claim 34, said composition being in the form of a gel or paste, said distributing step comprising the step of applying the composition as a layer into or adjacent said area.
37. The method of claim 34, said composition being absorbed onto a wipe, said applying step comprising the step of applying the composition by contacting the wipe into or adjacent said area.
38. A method of decontaminating an area containing a biological agent comprising the steps of: providing a carrier composition having less than about 10% by weight water; distributing said carrier composition into or adjacent a contaminated area to collect the biological agent; and deactivating the biological agent by adding a biocide to said carrier, said carrier including a component different than said biocide and selected from the group consisting of straight or branched chain, substituted or unsubstituted halogenated C3-C15 hydrocarbons, Cl -C 12 straight or branched chain alkyl alcohols, and mixtures thereof.
39. The method of claim 38, said biocide selected from the group consisting of biocidally effective organic peroxides, oxides, aldehydes, phenols, napthas and acids, quaternary ammonium compounds, transition metals and salts thereof, the halogens, compounds containing a halogen, N, S or B atom, ozone and mixtures thereof.
40. The method of claim 39, said biocide selected from the group consisting of formaldehyde, glutaraldehyde, peroxyacetic acid, ozone, the alkali metal hypochlorites, chlorine, chlorine dioxide, alkylene oxides, 2-amino-2-methyl- 1 -propanol, cetyltrimethylammo- nium bromide, cetylpyridinium chloride, 2,4,4-trichloro-2-hydroxydiphenylether, l-(4- chlorophenyl)-3-(3,4-dichlorophenyl) urea, zinc salts, pentachlorophenol, copper naphthenate, tributyltin oxide, dichlorophen, p-nitrophenol, p-chloro-m-xylenol, beta-naphthol, 2,3,5,6- tetrachloro-4-(methyl sulfonyl)-pyridine, salicylanilide, bromoacetic acid, alkyl quaternary ammonium acetate, sodium ethyl mercuric thiosalicylate, sodium orthophenyl phenate, n-alkyl (C12 to C18) dimethyl benzyl ammonium chloride, organoborates, 2,2-(l- methyltrimethylenedioxy)-bis-(4-methyl-l,3,2- dioxaborinane), 2,2-oxybis(4,4,6-trimethyl)- 1,3,2-dioxaborinane, ethylene glycol monomethyl ether, parahydroxy benzoates, organic boron compounds, 8-hydroxyquinoline, sodium pentachlorophenate, dimethylethylalkylbenzyl ammonium chloride, alkylammonium salts of 2-pyridinethiol- 1 -oxide, 1 ,3,5-triethylhexahydro- 1,3,5-triazine, strontium chromate, halogenated phenols, silver salts, silver oxide, silver, silver sulfadiazine, copper, copper salts, sodium dichloro-s-triazinetrione, substituted paraffins, triethyltin chloride, 2,4,5-trichlorophenol, 2,4,6-trichlorophenol, 2,2-thiobis(3,4,6- trichlorophe- nol), l,3-dichloro-5,5-dimethylhydantoin, tris(hydoxy-methyl)nitromethane, nitroparaffins, hexahydro-1 ,3,5-tris(2-hydroxy-ethyl)-s-triazine, 1 ,3,5-tris(tetrahydro-2-furanyl)-methyl- hexahydro-s-triazine, methyl bisthiocyanate, 2,2-dibromo-3-nitrilopropionamide, β-bromo-β- nitrostyrene, fluorinated compounds, pentachlorophenol, dichlorophene, orthophenyl phenol, di- bicyclo-(3,l , 1 or 2,2, 1 )-heptyl and di-bicyclo-(3 , 1 , 1 or 2,2, 1 )-heptenyl polyamines, and mixtures thereof.
41. The method of claim 38, said carrier including a substituted fluorinated C3-C15 hydrocarbon.
42. The method of claim 41, said carrier selected from the group consisting ofmethoxynonaIluorobutane and 2-trifiuoromethyl-3-ethoxydodecofiuorohexane.
43. The method of claim 38, said carrier comprising a mixture of a C1-C6 alkyl alcohol and a substituted fluorinated C3-C15 hydrocarbon.
44. The method of claim 43 , said C 1 -C6 alkyl alcohol being present at a level of up to about 20% by weight in said carrier.
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US10238107B2 (en) 2014-07-31 2019-03-26 Kimberly-Clark Worldwide, Inc. Anti-adherent composition
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