WO2011009031A2 - Compositions virucides et leurs utilisations - Google Patents

Compositions virucides et leurs utilisations Download PDF

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Publication number
WO2011009031A2
WO2011009031A2 PCT/US2010/042239 US2010042239W WO2011009031A2 WO 2011009031 A2 WO2011009031 A2 WO 2011009031A2 US 2010042239 W US2010042239 W US 2010042239W WO 2011009031 A2 WO2011009031 A2 WO 2011009031A2
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composition
weight per
per volume
sodium dodecyl
dodecyl sulfate
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PCT/US2010/042239
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English (en)
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WO2011009031A3 (fr
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Michael Patrick Doyle
Tong Zhao
Jennifer L. Cannon
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University Of Georgia Research Foundation
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Publication of WO2011009031A2 publication Critical patent/WO2011009031A2/fr
Publication of WO2011009031A3 publication Critical patent/WO2011009031A3/fr
Priority to US13/350,315 priority Critical patent/US20120121679A1/en

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    • 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
    • A01N37/42Biocides, 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 within the same carbon skeleton a carboxylic group or a thio analogue, or a derivative thereof, and a carbon atom having only two bonds to hetero atoms with at the most one bond to halogen, e.g. keto-carboxylic acids

Definitions

  • the present disclosure is generally related to microbicidal compositions and particularly compositions having viricidal activity and to methods of use thereof.
  • Enveloped or "lipophilic” viruses have an outer lipid-based membrane enveloping the capsid (comprised solely of capsomere proteins) that in turn protects the innermost viral genetic material.
  • the enveloping membrane contains both viral and host cell proteins, and is acquired during budding from the host cell at the end of the viral replication process.
  • Enveloped viruses include respiratory syncitial virus (RSV), and coronavirus, as well as influenza, measles, Hepatitis B and C and Herpes simplex viruses.
  • RSV respiratory syncitial virus
  • coronavirus as well as influenza, measles, Hepatitis B and C and Herpes simplex viruses.
  • Non-enveloped viruses do not have an enveloping membrane; their outer surface is the protein capsid.
  • viruses include caliciviruses (norovirus and sapovirus), astrovirus, rhinovirus, rotavirus, adenovirus, Hepatitis E virus and Hepatitis A virus.
  • Non-enveloped viruses may be less susceptible to conventional viricides than enveloped viruses.
  • Typical antimicrobial agents such as alcohol that affect cell membranes may also affect the outer membrane of an enveloped virus, but as a sole active agent may have little or no effect on the capsids of either virus type, either enveloped or non-enveloped.
  • Non-enveloped viruses are particularly difficult to adequately disinfect from environmental surfaces. Strong oxidizers like peracetic acids and bleaches inactivate most viruses with sufficient time, concentration, and no organic load, but they cannot be used on many surfaces without damaging them. Traditional disinfectants based on quaternary ammonium compounds (QACs) as the sole active agent may also have little or no effect on such viruses.
  • QACs quaternary ammonium compounds
  • Norovirus a member of the family Caliciviridae, is one of the most difficult viruses to disinfect.
  • Human noroviruses (NoV) have emerged globally as the leading cause of nonbacterial gastroenteritis and the second most frequent agent of severe childhood
  • MNV Murine Norovirus
  • FCV Feline Calicivirus
  • a levulinic acid plus sodium dodecyl sulfate solution has been shown to be effective in inactivating Salmonella and E. coll 0157:1-17 on fresh lettuce by greater than 6 log CFU/g in less than 20 sec.
  • this composition is highly effective in the presence of organic debris, making it an attractive alternative to chlorine-based wash treatments that become less effective with an increase in organic load.
  • compositions comprising surfactants and an acid, particularly, but not limited to, levulinic acid that has a synergistic effect in reducing the viability of a virus population compared to the efficacy of the individual compounds.
  • This synergy allows the formulation of compositions where the active agents (including an acid and a surfactant) are present at concentrations effective to inactivate viruses on surfaces, including human skin.
  • the viricidal compositions disclosed herein are efficacious without damaging the surface to which they may be applied, or even altering the organoleptic properties of a treated food substance.
  • the viricidal compositions and the wipes containing such compositions are suitable for sanitizing any surface suspected of having a viral load thereon or where it is desirable to ensure that a viral load is as low as possible.
  • a liquid antimicrobial composition comprising: (i) a surfactant, where the total concentration of the surfactant in said composition is about 0.05% to about 5% by weight per volume of solvent, and (ii) a monoprotic organic acid comprising a carbon backbone of 3 to 13 carbons, wherein the total concentration of the acid in said antimicrobial composition is about 0.2% to about 20% by weight per volume of solvent, and (iii) a solvent, and where the antimicrobial composition is effective in reducing the viability of a virusl population.
  • the monoprotic organic acid can have the general structure of:
  • n is an integer selected from 1 to 10.
  • the surfactant can be an anionic surfactant selected from the group consisting of: sodium dodecyl sulfate, sodium laureth sulfate, cetylpyridinium chloride, cetylpyridinium bromide, and benzalkonium chloride.
  • the solvent can be water or an alcohol :water mix, where the alcohol is selected from the group consisting of ethanol, propanol, butanol, propylene glycol, diethylene glycol, dipropylene glycol, or a mixture thereof.
  • the composition can further comprise a cationic agent selected from the group consisting of: benzalkonium chloride, benzethonium chloride, triclocarban, tricolsan, chlorhexidine, and any combination thereof.
  • a cationic agent selected from the group consisting of: benzalkonium chloride, benzethonium chloride, triclocarban, tricolsan, chlorhexidine, and any combination thereof.
  • the compositions may be formed as a foam having a cylinder foam test half life of at least ten minutes.
  • the surfactant is sodium dodecyl sulfate.
  • the monoprotic organic acid is levulinic acid.
  • antimicrobial compositions can comprise about 0.5% to about 5% sodium dodecyl sulfate by weight per volume in water and about 2% to about 20% levulinic acid by weight per volume in water.
  • the composition consists essentially of about 3% sodium dodecyl sulfate by weight per volume in water and about 5% levulinic acid by weight per volume in water.
  • the composition consists essentially of about 2% sodium dodecyl sulfate by weight per volume in water and about 5% levulinic acid by weight per volume in water.
  • Another aspect of disclosure encompasses a composition substantially free of a solvent and comprising: (i) a surfactant, and (ii) a monoprotic organic acid comprising a carbon backbone of 3 to 13 carbons, wherein the surfactant and the monoprotic organic acid are in a weight ratio of between about 1 :400 to about 25:1 , and wherein when the composition is mixed with a solvent provides an antimicrobial composition effective in reducing the viability of a virus population.
  • the composition can comprise a surfactant and a monoprotic organic acid, and where the surfactant can be sodium dodecyl sulfate, and the monoprotic organic acid can be levulinic acid.
  • the weight ratio of sodium dodecyl sulfate to levulinic acid can be about about 1 :2 to about 1 :3.
  • Still another aspect of the present disclosure provides embodiments of a method of reducing the viability of a population of viruses, the method comprising obtaining an antimicrobial composition comprising about 0.05% to about 5% sodium dodecyl sulfate by weight per volume in water and about 0.2% to about 20% levulinic acid by weight per volume in water and contacting a population of viruses with said antimicrobial composition, whereby the viability of the virus population is reduced.
  • the virus population is disposed on a non-liquid surface.
  • the composition can comprise about 3% sodium dodecyl sulfate by weight per volume in water and about 5% levulinic acid by weight per volume in water.
  • the composition can comprise about 2% sodium dodecyl sulfate by weight per volume in water and about 5% levulinic acid by weight per volume in water.
  • the composition can be disposed on a flexible base material and the composition is applied to a surface desired to have a reduced viable viral load thereon.
  • the flexible base material includes a positive ionic charge thereon.
  • the antimicrobial composition is applied to a virus population as a liquid wash, a spray, a foam, a paste, a cream, a gel, or a wipe.
  • Yet another aspect of the present disclosure encompasses embodiments of sanitizing wipes comprising an flexible base support material and an antimicrobial composition absorbed thereon, wherein the antimicrobial composition comprises (i) a surfactant, wherein the total concentration of surfactant in said composition is about 0.05% to about 5% by weight per volume of solvent, and (ii) a monoprotic organic acid comprising a carbon backbone of 3 to 13 carbons, wherein the total concentration of the acid in said antimicrobial composition is about 0.2% to about 20% by weight per volume of solvent, and wherein the antimicrobial composition is effective in reducing the viability of a virus population.
  • the antimicrobial composition comprises (i) a surfactant, wherein the total concentration of surfactant in said composition is about 0.05% to about 5% by weight per volume of solvent, and (ii) a monoprotic organic acid comprising a carbon backbone of 3 to 13 carbons, wherein the total concentration of the acid in said antimicrobial composition is about 0.2% to about 20% by weight per
  • the flexible base support material can have a surface positive charge thereon.
  • the antimicrobial composition can comprise about 0.5% to about 5% by weight per volume in water sodium dodecyl sulfate and about 0.2% to about 20% by weight per volume in water levulinic acid.
  • the composition can comprise about 5% by weight per volume in water sodium dodecyl sulfate and about 5% by weight per volume in water levulinic acid.
  • the composition can comprise about 2% by weight per volume in water sodium dodecyl sulfate and about 5% by weight per volume in water levulinic acid.
  • Fig. 1 is a graph showing the log reduction of MNV dried on stainless steel coupons after treatment with dry wipes of various surface charges using 1 or 5 wiping motions. Error bars indicate standard deviation.
  • Fig. 2 is a graph showing the log reduction of murine norovirus (MNV) dried on stainless steel coupons after treatment with wet wipes of various surface charges in combination with levulinic acid plus sodium dodecyl sulfate and compared to water using 1 or 5 wiping motions. Error bars indicate standard deviation.
  • Fig. 3 is a graph showing the log reduction of Hepatitis A virus (HAV) dried on stainless steel coupons after treatment with dry wipes of various surface charges using 1 or 5 wiping motions. Error bars indicate standard deviation.
  • HAV Hepatitis A virus
  • Fig. 4 is a graph showing the log reduction of HAV dried on stainless steel coupons after treatment with wet wipes of various surface charges in combination with levulinic acid plus sodium dodecyl sulfate and compared to water using 5 wiping motions. Error bars indicate standard deviation.
  • Fig. 5 is a graph showing the log reduction of Salmonella enterica dried on stainless steel coupons after treatment with dry wipes of various surface charges using 1 or 5 wiping motions. Error bars indicate standard deviation.
  • Fig. 6 is a graph showing the log reduction of Salmonella enterica dried on stainless steel coupons after treatment with wet wipes of various surface charges in combination with levulinic acid plus sodium dodecyl sulfate and compared to water using 1 or 5 wiping motions. Error bars indicate standard deviation.
  • Fig. 7 is a graph showing the log reduction of MNV dried on latex gloves after treatment with wet wipes of positive and neutral charge in combination with levulinic acid plus sodium dodecyl sulfate and compared to water using 1 or 5 wiping motions. Error bars indicate standard deviation.
  • Fig. 9 is a graph showing the log reduction of MNV on the surface of grapes after treatment with 5% levulinic acid plus 2% sodium dodecyl sulfate or water for 1 min or 5 mins.
  • Embodiments of the present disclosure will employ, unless otherwise indicated, techniques of medicine, organic chemistry, biochemistry, molecular biology, pharmacology, and the like, which are within the skill of the art. Such techniques are explained fully in the literature.
  • compositions comprising, “comprising,” “containing” and “having” and the like can have the meaning ascribed to them in U.S. Patent law and can mean “ includes,” “including,” and the like; “comprising” or “consists essentially” or the like, when applied to methods and compositions encompassed by the present disclosure refers to compositions like those disclosed herein, but which may contain additional structural groups, composition components or method steps (or analogs or derivatives thereof as discussed above).
  • compositions or methods do not materially affect the basic and novel characteristic(s) of the compositions or methods, compared to those of the corresponding compositions or methods disclosed herein.
  • "Comprising” or “consists essentially” or the like when applied to methods and compositions encompassed by the present disclosure have the meaning ascribed in U.S. Patent law and the term is open-ended, allowing for the presence of more than that which is recited so long as basic or novel characteristics of that which is recited is not changed by the presence of more than that which is recited, but excludes prior art embodiments.
  • the following definitions are provided and should be used unless otherwise indicated.
  • antiviral and the term “viricide” as used herein are intended to include any compound or composition that inactivates or decreases the ability of a virus to infect a cell and/or replicate.
  • an effective antiviral or viricide will reduce the viral infectivity by at least a 2-5 log factor for a single application of the compound, although a 7 log factor can also be contemplated. Higher levels of reduction in viral infectivity may be achieved by repeat application of the compound or if used in conjunction with other cleansing or sanitizing agents. It is contemplated that an "antimicrobial” as herein referred may include, in addition to an antiviral activity other antimicrobial activity including, but not limited to, an antibacterial activity.
  • the term "acid” or "organic acid” as used herein refers to a compound having a hydrocarbon chain and an acid group covalently bound to the hydrocarbon chain.
  • the hydrocarbon chain can be of any length and can be a straight chain or branched chain.
  • the most common organic acids are the carboxylic acids whose acidity is associated with their carboxyl group -COOH.
  • additional compounds that lack a carboxylic function group can still function as an acid in accordance with the present invention if the compound ionizes in aqueous solution to yield hydrogen ions. Accordingly, eugenol is considered an acid within the context of the present invention due to the electron withdrawing properties of the phenol ring on the hydroxyl group subsitutent.
  • Sulfonic acids containing the group - OSO 3 H, are another typical, but relatively stronger group of organic acids.
  • the organic acid is a carboxylic acid comprising a maximum of 3 to 8 carbon atoms.
  • the organic acids used in the embodiments of the present disclosure may also include additional functional groups extending from the hydrocarbon backbone.
  • the carbon chain of the orgainic acid is functionalized by a hydroxyl, a carbonyl, an amino, an alkylamino, a sulfonyl, or a thiol group.
  • a monoprotic acid is an acid that is able to donate one proton per molecule during ionization.
  • a quaternary ammonium cation is a compound of the general structure:
  • R 1 , R 2 , R 3 , and R 4 are independently selected from the group consisting of C 1 - C 20 alkyl and salts thereof.
  • benzalkonium chloride refers to a single
  • alkylbenzyldimethylammonium chloride of the general structure
  • n is an integer selected from the group consisting of 6, 8, 10, 12, 14, 16, 18 and 20, or mixtures of two or more such compounds.
  • surface refers to a surface that is desired to be sanitized such as, but not limited to, a glove (latex or non-latex) including surgical gloves, a tool, a surgical tool or apparatus, a machine, equipment, a structure, a building, play materials, bathroom interiors, or other household surfaces, or the like, or the skin surface of an animal or human.
  • food processing surfaces include surfaces of food processing or preparation equipment (e.g., slicing, canning, or transport equipment, including flumes), of food processing wares (e.g., utensils, dishware, wash ware, and bar glasses), and of floors, walls, or fixtures of structures in which food processing occurs.
  • Food processing surfaces are found and employed in food anti-spoilage air circulation systems, aseptic packaging sanitizing, food refrigeration and cooler cleaners and sanitizers, ware washing, blancher cleaning, food packaging materials, cutting boards, beverage chillers and warmers, meat chilling or scalding equipment, cooling towers, food processing garment areas (including drains).
  • Play material surfaces include, but are not limied to, surfaces of toy articles, playground equipment, cards and poker chips.
  • Bathroom surfaces include such as sinks, toilets, walls, door handles, and fixtures.
  • compositions and methods according to the disclosure are especially useful, therefore, for sanitizing, thereby reducing the level of a viable population on the surfaces of buildings where large numbers of individuals may congregate or be confined such as in a hotel or cruise ship, hospital or medical offices, day cares, schools, or military barracks, or where the individuals have access to surfaces where repeated handling or animal or human contact can transmit or have the potential to transmit and cross-contaminate with bacterial and viral organisms.
  • the present compositions have been found to remain effective even in an organic-rich environment (high organic load).
  • the compositions can be used as a single wash treatment of surfaces such as food preparation surfaces that may contain such materials in addition to pathogenic microbes, but the compositions can also be used as a repeat treatment or a treatment used in conjunction with other cleansers or sanitizers which can further assist in the removal of organic debris.
  • cylinder foam test refers to a test for measuring both the foamability of compositions and the persistence of the foamed state.
  • the test comprises the steps of placing a test composition into a stoppered, graduated cylinder so that the composition occupies a predetermined height of the cyclinder (e.g., about 1/3 to about 1/2 of the height of the stoppered, graduated cylinder).
  • the stoppered, graduated cylinder is then inverted approximately 10 times to generate a foam.
  • the height of foam is measured immediately after the inverting step as a measure of the foamability of the composition.
  • the foamed composition is then left undisturbed to determine the foam half life (time required for the foam to lose half its height in the graduated cylinder).
  • the cylinder foam test is conducted at room temperature under 1 standard atmosphere pressure (i.e., 100 kPa (about 750.01 mm Hg) or 29.53 in Hg).
  • Acid stable, non-enveloped enteric viruses such as human norovirus and Hepatitis A virus (HAV) are not readily inactivated by treatment with organic acids, surfactants, or detergents.
  • levulinic acid and SDS provide only minimal ( ⁇ 2 log CFU/ml) inactivation of bacterial pathogens, but the combination acts synergistically for much greater levels of inactivation.
  • compositions that comprises generally recognized as safe (GRAS) chemicals, that has efficacy in rapidly killing both enveloped and non-enveloped viruses on all substrates, absent negative impacts to the environment or to the surface to which the composition is applied. It would also be beneficial for such a composition to have long-lasting residual effects, so that the surfaces would remain free of active viruses long after the application of the composition to the surface.
  • GRAS safe
  • compositions comprising surfactants, and particularly, but not intended to be limiting in any way, levulinic acid that have a synergistic effect in reducing the viability of a virus population compared to the efficacy of the individual compounds.
  • This synergy allows the formulation of compositions where the active agents (including an acid and a surfactant) are present at concentrations effective to inactivate viruses on surfaces, including human skin, between 10 2 - and 10 7 -fold.
  • the viricidal compositions disclosed herein are efficacious with little or no damage to the surface to which they may be applied, or even altering the organoleptic properties of a treated food substance.
  • the viricidal compositions and the wipes containing such compositions are suitable for sanitizing any surface suspected of having a viral load thereon or where it is desirable to reduce a viral load.
  • compositions of the disclosure include human skin (particularly hands) or surfaces likely to come in contact with human skin, as well as the surfaces of food substances such as poultry, meat or fresh produce, and surfaces that come in contact with food substances such as poultry, meat or fresh produce.
  • compositions as described in the present disclosure while comprising a surfactant and a monoprotic acid as the synergistically cooperating active viricidal agents, may further include such as, but not limited to, L-lysine, peroxacetic acid, N-halamine, D- limonene, hydrogen peroxide, Polysorbate 20, Polysorbate 80, allylisothiocyanate, eugenol, cetylpyridinium chloride, cetylpyridinium bromide, ethanolamine, EDTA or other compounds that may serve to increase the antiviral activity of the composition.
  • L-lysine such as, but not limited to, L-lysine, peroxacetic acid, N-halamine, D- limonene, hydrogen peroxide, Polysorbate 20, Polysorbate 80, allylisothiocyanate, eugenol, cetylpyridinium chloride, cetylpyridinium bromide, ethanolamine, EDTA or other compounds
  • the antiviral compositions herein described may be deposited on or within a flexible base and pliable laminar material that may then be used as a wipe to spread the antiviral composition over a surface desired to be sanitized.
  • the present disclosure therefore, further encompasses embodiments of a wipe, including a hand wipe or other flexible base material including but not limited to, a fabric, a woven mesh, a pad, a paper towelette, a paper towel, and the like, that may absorb and/or retain thereon a quantity of the liquid antimicrobial composition.
  • the wipe may then be used to apply the antimicrobial solution to a surface that it is desired to sanitize by reducing or eleiminating the viability of any microorganisms.
  • Hand wipes can be devised that have both cleansing and sanitizing properties, making them an appealing method of delivery of antimicrobial compositions according to the present disclosure for reducing microbial populations on hand surfaces or other surfaces desired to be
  • Suitable flexible base and pliable materials for use in the methods and compositions of the present disclosure include, but are not limited to, a fabric composed partially or entirely of natural fibers including cotton, flax, linen, hemp, and the like, or partially or entirely of artificial materials such as nylon, DACRON. RTM, rayon, polyester, polythene, and the like.
  • the most suitable flexible base materials may be woven or molded as meshes that provide spaces for impregnation of viricidal compositions according to the present disclosure.
  • the fibers of the flexible base material may be hollow to adsorb an increased amount of the antiviral composition.
  • a particularly useful material for impregnating with the antiviral compositions according to the present disclosure are those materials have a net positive ionic charge thereon. Such materials have an increased capacity to attract negatively charged microorganisms thereby furthering the removal of viral and bacterial particles from a surface and contacting the particles with the antimicrobial composition impregnated in the wipe material.
  • a wipe impregnated with the antimicrobial composition of the present disclosure provides a convenient means of delivery of the composition to a surface to be sanitized
  • the composition may be contacted with the surface to be treated by a variety of dispensing methods, including by such as, but not limited to, spraying, wiping, dousing, and the like.
  • Particularly useful is applying the composition as a foam that prolongs the application of the antimicrobial to the applied surface and will assist in the physical removal of dislodged viral, bacterial, and organic debris from the treated surface.
  • the compositions of the disclosure may be formulated to provide a foam having mechanical properties adequate to provide the desired prolonged treatment or debris removal activity.
  • compositions herein described can provide the foaming action or additional foaming agents known in the art may be included.
  • the concentration of total acid present in the composition can be about 0.2 to about 20% by weight per volume in water (2-200 grams/L) and the concentration of total surfactant is about 0.05% to about 5% by weight per volume in water (0.5-50 grams/L).
  • the acid is an acid that has been classified by the US Department of Agriculture as being Generally Regarded As Safe (GRAS) and includes, but is not limited to, levulinic acid, caprylic acid, caproic acid, citric acid, eugenol, adipic acid, tartaric acid, fumaric acid, lactic acid, phosphoric acid, hydrochloric acid, succinic acid, malic acid and sorbic acid.
  • GRAS Generally Regarded As Safe
  • the surfactant can be selected from any ionic (cationic or anionic) or non-ionic surfactants.
  • Surfactants for application to the human skin or which might be in contact with foodstuffs consumed by animals or humans preferably should be compatible for human use and not lead to adverse reactions by the recipients.
  • the surfactant component may comprises one or more functionalized organic acids having a hydrocarbon chain length of 2 to 25 carbons, wherein the functionalizing group is selected from hydroxyl, amino carbonyl, sulphonyl, phosphate and thiol groups.
  • Such surfactants are known in the art in the field of food industry and include, for example, sodium dodecyl sulfate (SDS), sodium laureth sulfate (SLS; or sodium lauryl ether sulfate, SLES), cetylpyridinium chloride (CPC), cocamide MEA (MEA), cocamide DEA (DEA), benzalkonium chloride and ethylenediaamine tetraacetic acid (H 4 EDTA) and salts thereof such as Na 4 EDTA and Na 2 H 2 EDTA.
  • SDS sodium dodecyl sulfate
  • SLS sodium laureth sulfate
  • SLES sodium lauryl ether sulfate
  • CPC cetylpyridinium chloride
  • MEA cocamide MEA
  • DEA cocamide DEA
  • Such substituents can be selected from -PO 3 , C 1 -C 8 hydroxylalkyl and C 5 -C 6 aryl hydroxyl groups.
  • the surfactant may also be selected from the group consisting of mono-, di-, tri- and tetra- alkylammonium halides, sulfates and phosphates wherein at least one of the alkyl substituents of the alkylammonium halide comprises at least carbon atoms and more typically 10-25 carbon atoms.
  • the surfactant can be selected from the group consisting of sodium dodecyl sulfate, sodium laureth sulfate, cetylpyridinium chloride, cetylpyridinium bromide and benzalkonium chloride and the organic acid is levulinic acid.
  • compositions disclosed herein may further comprise two or more different acids or two or more different surfactants provided that the total concentration of acid present in the composition is about 0.2% to about 20% by weight per volume in water (2-200 grams/L) and the total concentration of surfactant is about 0.05% to about 5% by weight per volume in water (0.5-50 grams/L).
  • a viricidal composition can be provided that comprises levulinic acid and a surfactant, where the total concentration of acid in said composition is about 0.5% to about 5.0% (w/v) and the total concentration of surfactant in said composition is about 0.5% to 5% (w/v).
  • compositions disclosed herein are capable of reducing resident virus populations in liquids, on solid surfaces, the surfaces of food substance (or surfaces coming in contact with food substances), or on human skin (or on surfaces coming in contact with human skin) by a factor equal to, or greater than, 10 2 , including by a factor of at least 10 3 , and between a factor of 10 3 and a factor of 10 7 , using a combination of an acid and surfactant at
  • compositions of the disclosure can provide an accumulative effect whereby each application can reduce the viral load by 1-3 log so that after three applications the viral load can be reduced by a factor of 7 log or more.
  • the active ingredients of the present compositions i.e., the acid and surfactant
  • the antimicrobial (viricidal) compositions of the present disclosure comprise a linear monoprotic organic acid and an ionic long chain (C 8 -C 30 ) surfactant.
  • the organic acid is preferably, but not limited to, a linear monoprotic organic acid comprising a carbon backbone of 3 to about 13 carbons.
  • a viricidal composition comprising an acid and a surfactant, wherein the general structure of the acid is CH 3 (CH 2 ) H1 COOH, with m being an integer selected from 2-12, and the surfactant can be, but is not limited to, sodium dodecyl sulfate (SDS), sodium laureth sulfate (SLS), or sodium lauryl ether sulfate (SLES), cetylpyridinium chloride (CPC) and benzalkonium chloride.
  • SDS sodium dodecyl sulfate
  • SLS sodium laureth sulfate
  • SLES sodium lauryl ether sulfate
  • CPC cetylpyridinium chloride
  • benzalkonium chloride benzalkonium chloride
  • the acid has the general structure CH 3 (CH 2 ) m COOH, with m being an integer selected from 2-12 and the surfactant can be sodium dodecyl sulfate (SDS), sodium laureth sulfate (SLS), or sodium lauryl ether sulfate (SLES).
  • SDS sodium dodecyl sulfate
  • SLS sodium laureth sulfate
  • SLES sodium lauryl ether sulfate
  • composition can comprise an acid of the general structure CH 3 (CH 2 ) m COOH, or
  • n is an integer selected from 1-10, and the surfactant is a cation of the general structure:
  • Ri, R 2 , R 3 , and R 4 are independently selected from the group consisting of C 1 -C 20 alkyl, and salts thereof.
  • Ri is C 6 -C 20 alkyl and R 2 , R 3 , and R 4 are independently selected from the group consisting of C 1 -C 2 alkyl.
  • Levulinic acid is an organic acid that can be produced cost effectively and in high yield from renewable feedstocks (Bozell, et al., (2000); Fang & Hanna (2002)). Its safety for humans has been widely tested and FDA has given it GRAS status for direct addition to food as a flavoring agent or adjunct (21 CFR, 172.515).
  • SDS Sodium dodecyl sulfate
  • GRAS status 21 CFR, 172.210
  • SDS Sodium dodecyl sulfate
  • It has been widely studied and is used as a surfactant in household products such as toothpastes, shampoos, shaving foams, and bubble baths.
  • the SDS molecule has a tail of 12 carbon atoms attached to a sulfate group, giving the molecule the amphiphilic properties required of a surfactant.
  • compositions of the disclosure may optionally further include one or more additional compounds to increase the antimicrobial activity spectrum, to provide a general cleansing activity, and/or to provide a commercially desirable product having a particular odor, color, consistency and the like such as including one or more compounds selected from the group consisting of peroxacetic acid, N-halamine, D-limonene (1-methyl-4-(prop-1- en-2-yl)-cyclohexene), hydrogen peroxide, acidic copper sulfate, an aliphatic alcohol, an aromatic alcohol, a polyquatemium, allylisothiocyanate, eugenol (4-Allyl-2-methoxyphenol), L-lysine, Polysorbate 20 (TWEEN 20.
  • additional compounds to increase the antimicrobial activity spectrum, to provide a general cleansing activity, and/or to provide a commercially desirable product having a particular odor, color, consistency and the like
  • additional compounds selected from the group consisting of peroxacetic acid, N-halamine,
  • RTM polyoxyethylene (20) sorbitan monolaurate), Polysorbate 80 (TWEEN 80. RTM; polyoxyethylene (20) sorbitan monooleate), ammonium lauryl sulfate, sodium laureth sulfate, benzalkonium chloride, cetylpyridinium chloride, EDTA, alcohols and polyquaterniums (including for example, polyquaternium-1 [Ethanol, 2,2', 2" - nitrilotris-, polymer with 1 ,4-dichloro-2-butene and N,N,N',N'-tetramethyl-2-butene- 1 ,4- diamine]; polyquaternium-2 [Poly[bis(2-chloroethyl) ether-alt-l,3-bis[3- (dimethylamino)propyl]urea]]; polyquaternium-4; polyquaternium-5 [copolymer of acrylamide and quaternized dimethylammoni
  • polyquaternium-14 polyquaternium-[acrylamide-dimethylaminoethyl methacrylate methyl chloride copolymer]; polyquaternium-16 [copolymer of vinylpyrrolidone and quaternized vinylimidazole]; polyquaterniurn-17; polyquaternium-18; polyquaternium-19.
  • the composition When the present composition is provided as a foam, the composition has a cellular structure that can be characterized as having several layers of air cells that provide the composition with a foamy appearance. It should be understood that the characterization of a foam refers to the existence of more than simply a few air bubbles and the foam can retain over 20, 30, 40, 50, 60 or 70% of its maximum height in a cylinder foam test 10 minutes after agitation ceases.
  • the foamed antimicrobial composition of the present disclosure can retain at least 20% of its height in a cylinder foam test 5 minutes after agitation is ceased.
  • the antimicrobial compositions disclosed herein can be formed as a foam using simple mechanical foaming heads known to those skilled in the art that function by mixing air and the composition to create a foamed composition.
  • the use of known chemical foaming mechanisms is also suitable for forming foams in accordance with the present invention.
  • the antimicrobial composition can include ingredients that create foam as a result of a chemical interaction, either with other ingredients in the composition, or with substances present in the applicable environment. These components can be provided as a 2-part composition that can be combined when foaming is desired.
  • Foaming can be accomplished, for example, using a foam application device such as a foaming soap dspenser, tank foamer or an aspirated wall mounted foamer, e.g., employing a foamer nozzle of a trigger sprayer.
  • foaming can be accomplished by placing the composition in a fifteen gallon foam application pressure vessel, such as a fifteen gallon capacity stainless steel pressure vessel with mix propeller. The foaming composition can then be dispensed through a foaming trigger sprayer.
  • a wall mounted foamer can use air to expel foam from a tank or line.
  • the antimicrobial compositions disclosed herein can be optionally administered to a surface as a foam.
  • the foam can be prepared by mixing air with the antimicrobial composition through use of a foam application device.
  • Mechanical foaming heads that can be used according to the invention to provide foam generation include those heads that cause air and the foaming composition to mix and create a foamed composition. That is, the mechanical foaming head causes air and the foaming composition to mix in a mixing chamber and then pass through an opening to create a foam.
  • Suitable mechanical foaming heads that can be used according to the invention include those available from Airspray International, Inc. (Pompano Beach, FIa.), and from Zeller 35, a division of Crown Cork and Seal Co. Suitable mechanical foaming heads that can be used according to the invention are described in, for example, U.S. Pat. No. D- 452,822; U.S. Pat. No. D-452,653; U.S. Pat. No. D-456,260; and U.S. Pat. No. 6,053,364.
  • Mechanical foaming heads that can be used according to the invention includes those heads that are actuated or intended to be actuated by application of finger pressure to a trigger that causes the foaming composition and air to mix and create a foam. That is, a person's finger pressure can cause the trigger to depress thereby drawing the foaming composition and air into the head and causing the foaming composition and air to mix and create a foam.
  • Foam boosting agents can be added to the antimicrobial compositions to enhance either foamability and/or longevity of the formed foam, such as, but not limited to, glycols, glycol ethers, derivatives of glycol ethers, and mixtures thereof.
  • Suitable glycols include those having at least four carbon atoms such as hexylene glycol.
  • the viricidal compositions of the disclosure can further comprise an anti-foam or suds suppression agent. Incorporation of said agents is particularly desired for applications in which the viricidal compositions will be subjected to agitation in conjunction with the treatment of food substances (e.g., viricidal wash solutions).
  • the viricidal compositions may comprise an anti-foam or suds suppression agent, present at a level of from about 0.0001% to about 15%, or about 0.001 % to about 20%, or about 0.005% to about 5.0% by weight of the viricidal composition.
  • Suitable suds suppressing systems for use herein may comprise essentially any known anti-foam compound that exhibits stability at a pH of about 2.0 to about 4.5, including, but not limited to, those selected from the group consisting of silicone antifoam compounds, silicone emulsions, 2-alkyl and alkanol anti-foam compounds, Antifoam A, mineral oil emulsions, hydrocarbon oil emulsions, polyalkylene emulsions and combinations thereof.
  • Silicone suds suppressors can be the compounded types known for use in antimicrobial compositions, including, for example, polydimethylsiloxanes having
  • Such compounds may be compounded with silica and/or with surface-active nonsilicon components, as illustrated by a suds suppressor comprising 12% silicone/silica, 18% stearyl alcohol and 70% starch.
  • the viricidal composition according to the disclosure can comprise about 0.05 to about 5% sodium dodecyl sulfate by weight per volume in water, about 0.2 to about 20% levulinic acid by weight per volume in water and, optionally: 1) about 0.05% to about 70%, or about 0.05% to about 62%, or about 0.05% to about 20% or about 0.05% to about 1%, of an alcohol solvent.
  • the alcohol solvent is about 50% to about 80% or about 75% to about 85%.
  • Suitable alcohol solvents include, but are not limited to, ethanol, propanol, butanol, propylene glycol, diethylene glycol, dipropylene glycol and mixtures thereof; 2) about 0.05% to about 20% or about 0.05% to about 5%, or about 0.05% to about 1 % of a cationic agent selected from the group consisting of benzalkonium chloride, benzethonium chloride, triclocarban, tricolsan, chlorhexidine and mixtures thereof; 3) about 0.05% to about 5%, or about 0.05% to about 2%, or about 0.05% to about 1 % of a heavy metal salt selected from the group consisting of silver, zinc, copper and mixtures thereof.
  • a cationic agent selected from the group consisting of benzalkonium chloride, benzethonium chloride, triclocarban, tricolsan, chlorhexidine and mixtures thereof
  • a heavy metal salt selected from the group consisting of silver, zinc, copper and mixtures
  • the present disclosure further provides composition substantially free of a solvent and comprising: a surfactant; and a monoprotic organic acid comprising a carbon backbone of 3 to 13 carbons, where the pharmaceutically acceptable surfactant and the monoprotic organic acid are in a weight ratio of between about 1 :400 to about 25:1 that when added to an appropriate solvent will provide an antimicrobial (antiviral) composition according to the present disclosure.
  • the viricidal compositions disclosed herein can be used to reduce the population of an undesirable virus on a surface. Successful reduction of a population of a virus can be achieved when the infectivity of a virus population is reduced by at least 2 log.
  • the viricidal compositions can be used to inactivate a wide range of viruses including, but not limited to, gastroenteritis viruses and their surrogates, caliciviruses such as Murine norovirus, Feline Calicivirus, Human Norovirus and Sapovirus, Human Rotavirus, Sapovirus, Astrovirus, Bocavirus; Hepatitis viruses, such as Hepatitis A and Hepatitis E virus; and respiratory viruses, such as Rhinovirus, Corona virus, Influenza virus, and Adenovirus serotypes.
  • gastroenteritis viruses and their surrogates caliciviruses such as Murine norovirus, Feline Calicivirus, Human Norovirus and Sapovirus, Human Rotavirus, Sapovirus, Astrovirus, Bocavirus
  • Hepatitis viruses such as Hepatitis A and Hepatitis E virus
  • respiratory viruses such as Rhinovirus, Corona virus, Influenza virus, and Adenovirus serotypes.
  • the viricidal compositions can be formulated in various carriers for administration to inactivate viruses on a surface.
  • the compositions can be formulated as a hand sanitizer (either as a water based or water free formulation) using standard techniques known to those skilled in the art.
  • the composition can be added to fibrous materials to formulate hand sanitizing wipes or towelettes for sanitizing hard surfaces.
  • Such sanitizing wipes may further include such components as alumina nanofibers, charged glass and the like, and which may aid in attracting charged microorganisms from the contaminated surface.
  • These additional compounds can be interwoven in such as NANOCERAM. RTM filters.
  • the viricidal compositions can be formulated as a packaging insert for fresh produce or meat products consisting of a cellulose-based material soaked in viricidal composition, wherein any virus present will be inactivated upon food contact with the insert.
  • the viricidal compositions can be encapsulated (using standard techniques) to provide delayed or prolonged release of the active components.
  • a packaging insert for fresh produce or meat products which consists of a cellulose based material soaked in a slow-release viricide composition for virus inactivation within the package (not necessarily coming into contact with the insert).
  • the viricidal composition can be provided as a foodstuff wash solution, optionally containing an antifoaming agent.
  • the composition is provided as a foaming decontamination spray for use on hard surfaces (especially in cruise- ships, daycares, hospitals, and the like).
  • MNV was rapidly inactivated on stainless steel surfaces using a 5% levulinic acid plus 2% sodium dodecyl sulfate solution and a 5% levulinic acid plus 2% sodium dodecyl sulfate foam, resulting in > 3 log reductions of MNV within 5 min of treatment, regardless of the presence of up to 10% organic material.
  • the levulinic acid plus sodium dodecyl sulfate solution disclosed herein therefore, demonstrates rapid efficacy against the Human Norovirus surrogates, MNV and FCV in solution and when used on the surfaces of stainless steel and in the context of organic debris.
  • the liquid sanitizer was also effective against Human Rhinovirus and, therefore, provides an alternative to alcohol-based sanitizers which have limited efficacy against non-enveloped viruses.
  • Combinations of 5% levulinic acid plus 2% sodium dodecyl sulfate were more effective than lower concentrations of levulinic acid plus sodium dodecyl sulfate (2% levulinic acid plus 1% sodium dodecyl sulfate and 5% levulinic acid plus 2% sodium dodecyl sulfate) and water.
  • Dry wipes regardless of charge or number of wipes were ineffective, resulting in ⁇ 1 log for removal of norovirus, Hepatitis A virus, and Salmonella enterica.
  • wet wipes particularly those carrying a cationic charge on the base material and those impregnated with levulinic acid plus sodium dodecyl sulfate sanitizer effectively reduced populations of MNV on stainless steel surfaces by > 1 log.
  • Multiple (5) wiping passages (motions) in most of the tested scenarios was more effective than a single wipe and the 5% levulinic acid plus 2% sodium dodecyl sulfate solution effectively reduced MNV on stainless steel surfaces by > 2 log after 5 wipes.
  • a liquid antimicrobial composition comprising: (i) a surfactant, where the total concentration of the surfactant in said composition is about 0.05% to about 5% by weight per volume of solvent, and (ii) a monoprotic organic acid comprising a carbon backbone of 3 to 13 carbons, wherein the total concentration of the acid in said antimicrobial composition is about 0.2% to about 20% by weight per volume of solvent, and where the antimicrobial composition is effective in reducing the viability of a virus population.
  • the monoprotic organic acid can have the general structure of:
  • n is an integer selected from 1 to 10.
  • the surfactant can be an anionic surfactant selected from the group consisting of: sodium dodecyl sulfate, sodium laureth sulfate, cetylpyridinium chloride, cetylpyridinium bromide, and benzalkonium chloride.
  • the solvent can be water or an alcohohwater mix, where the alcohol is selected from the group consisting of ethanol, propanol, butanol, propylene glycol, diethylene glycol, dipropylene glycol or a mixture thereof.
  • the composition can further comprise a cationic agent selected from the group consisting of: benzalkonium chloride, benzethonium chloride, triclocarban, tricolsan, chlorhexidine, and any combination thereof.
  • a cationic agent selected from the group consisting of: benzalkonium chloride, benzethonium chloride, triclocarban, tricolsan, chlorhexidine, and any combination thereof.
  • the compositions may be formed as a foam having a cylinder foam test half life of at least ten minutes.
  • the surfactant is sodium dodecyl sulfate.
  • the monoprotic organic acid is levulinic acid.
  • antimicrobial compositions can comprise about 0.05% to about 5% sodium dodecyl sulfate by weight per volume in water and about 2% to about 20% levulinic acid by weight per volume in water.
  • the composition consists essentially of about 5% sodium dodecyl sulfate by weight per volume in water and about 5% levulinic acid by weight per volume in water.
  • the composition consists essentially of about 2% sodium dodecyl sulfate by weight per volume in water and about 5% levulinic acid by weight per volume in water.
  • compositions substantially free of a solvent comprising: (i) a surfactant, and (ii) a monoprotic organic acid comprising a carbon backbone of 3 to 13 carbons, wherein the surfactant and the monoprotic organic acid are in a weight ratio of between about 1 :400 to about 25:1 , and wherein when the composition is mixed with a solvent provides an antimicrobial composition effective in reducing the viability of a virus population.
  • the composition can comprise a surfactant and a monoprotic organic acid, and where the surfactant can be sodium dodecyl sulfate, and the monoprotic organic acid can be levulinic acid.
  • the weight ratio of sodium dodecyl sulfate to levulinic acid can be about about 1 :2 to about 1 :5.
  • Still another aspect of the present disclosure provides embodiments of a method of reducing the viability of a population of viruses, the method comprising obtaining an antimicrobial composition comprising about 0.05% to about 5% sodium dodecyl sulfate by weight per volume in water and about 0.2% to about 20% levulinic acid by weight per volume in water and contacting a population of viruses with said antimicrobial composition, whereby the viability of the virus population is reduced.
  • the virus population can be disposed on a non-liquid surface.
  • the composition can comprise about 5% sodium dodecyl sulfate by weight per volume in water and about 5% levulinic acid by weight per volume in water.
  • the composition can comprise about 2% sodium dodecyl sulfate by weight per volume in water and about 5% levulinic acid by weight per volume in water.
  • the composition can be disposed on a flexible base material and the composition is applied to a surface desired to have a reduced viable viral load thereon.
  • the flexible base material includes a positive ionic charge thereon.
  • the antimicrobial composition is applied to a virus population as a liquid wash, a spray, a foam, a paste, a cream, a gel, or a wipe.
  • Yet another aspect of the present disclosure encompasses embodiments of sanitizing wipes comprising an flexible base support material and an antimicrobial composition absorbed thereon, wherein the antimicrobial composition comprises (i) a surfactant, wherein the total concentration of surfactant in said composition is about 0.05% to about 5% by weight per volume of solvent, and (ii) a monoprotic organic acid comprising a carbon backbone of 3 to 13 carbons, wherein the total concentration of the acid in said antimicrobial composition is about 0.2% to about 20% by weight per volume of solvent, and wherein the antimicrobial composition is effective in reducing the viability of a virus population.
  • the antimicrobial composition comprises (i) a surfactant, wherein the total concentration of surfactant in said composition is about 0.05% to about 5% by weight per volume of solvent, and (ii) a monoprotic organic acid comprising a carbon backbone of 3 to 13 carbons, wherein the total concentration of the acid in said antimicrobial composition is about 0.2% to about 20% by weight per
  • the flexible base support material can have a surface positive charge thereon.
  • the antimicrobial composition can comprise about 0.05% to about 5% sodium dodecyl sulfate by weight per volume in water and about 0.2% to about 20% levulinic acid by weight per volume in water.
  • the composition can comprise about 5% by weight per volume in water sodium dodecyl sulfate and about 5% by weight per volume in water levulinic acid.
  • the composition can comprise about 2% by weight per volume in water sodium dodecyl sulfate and about 5% by weight per volume in water levulinic acid.
  • the specific examples below are to be construed as merely illustrative, and not limitative of the remainder of the disclosure in any way whatsoever. Without further elaboration, it is believed that one skilled in the art can, based on the description herein, utilize the present disclosure to its fullest extent. All publications recited herein are hereby incorporated by reference in their entirety.
  • ratios, concentrations, amounts, and other numerical data may be expressed herein in a range format. It is to be understood that such a range format is used for convenience and brevity, and thus, should be interpreted in a flexible base manner to include not only the numerical values explicitly recited as the limits of the range, but also to include all the individual numerical values or sub-ranges encompassed within that range as if each numerical value and sub-range is explicitly recited.
  • a concentration range of "about 0.1 % to about 5%” should be interpreted to include not only the explicitly recited concentration of about 0.1 wt% to about 5 wt%, but also include individual concentrations (e.g., 1%, 2%, 5%, and 4%) and the sub-ranges (e.g., 0.5%, 1.1%, 2.2%, 3.5%, and 4.4%) within the indicated range.
  • the term "about” can include ⁇ 1%, ⁇ 2%, ⁇ 5%, ⁇ 4%, ⁇ 5%, ⁇ 6%, ⁇ 7%, ⁇ 8%, ⁇ 9%, or ⁇ 20%, or more of the numerical value(s) being modified.
  • RAW 264.7 cells ATCC# TIB-71
  • Crandell Reese Feline Kidney (CRFK) cells ATCC# CCL-94
  • DMEM Dulbecco's Modified Eagles Medium
  • FBS low endotoxin fetal bovine serum
  • FBS FBS
  • FBS FBS
  • Virus was harvested after complete CPE (cytopathic effect) was apparent (typically after 48 h) by three cycles of freeze-thawing. Cellular debris was removed by centhfugation for 10 min at 1 ,731 x g and the supernatant was filtered through a 0.2 ⁇ m membrane filter (Millipore, Billerica, MA) before storing as 1-4 ml aliquots at -70 0 C until use.
  • Manassas, VA Manassas, VA), supplemented with either (a) 5% low endotoxin FBS, penicillin (100 U/ml), and streptomycin (100 ⁇ g/ml) with 100 mM HEPES, and 10 mM sodium pyruvate for MNV or (b) 4% FBS, 1% L-glutamine and 1% non-essential amino acids for FCV.
  • Plaques were subsequently counted 5-8 h after a second agarose overlay (0.5% agarose diluted in deionized water and including 1% neutral red solution (Sigma-Aldrich, St. Louis, MO)) was added. Plates with 5 to 50 plaques were used to determine the virus titer in plaque forming units (PFU).
  • a second agarose overlay (0.5% agarose diluted in deionized water and including 1% neutral red solution (Sigma-Aldrich, St. Louis, MO)
  • a Most Probable Number (MPN) technique was employed. HeLa-Ohio cells were grown to 80-90% confluence in 96-well tissue culture dishes in complete MEM. Virus was serially diluted (10x) in PBS and inoculated onto eight replicate wells (50 ⁇ l each) per sample. Cells were incubated for 1 h at 33°C with 5% CO 2 with gentle rocking every 15 min. After removal of inoculums, cells were supplemented with complete MEM and incubated for an additional 48 hrs. Replicate wells were visually scored (positive for cytopathic effect (CPE) or negative) for virus infection and MPNs were determined using the Build 23 MPN Calculator. Virus log reductions for each treatment were determined by comparison to a positive control (serial dilution of virus stock).
  • CPE cytopathic effect
  • Partially purified virus cell culture lysate or concentrated virus cell culture lysate (0.1 ml) was added to each concentration of levulinic acid plus sodium dodecyl sulfate solution (0.9 ml) and mixed on a shaking platform (200 rpm) at 21 0 C.
  • plaques numbers on duplicate cell culture plates were averaged for each treatment group and compared to control plates containing the same quantity of virus, but without containing the levulinic acid plus sodium dodecyl sulfate solution.
  • Levulinic acid plus sodium dodecyl sulfate solutions prepared at 2% levulinic acid plus 1% sodium dodecyl sulfate, 5% levulinic acid plus 2% sodium dodecyl sulfate, 5% levulinic acid plus 1% sodium dodecyl sulfate or 5% levulinic acid plus 2% sodium dodecyl sulfate concentrations were used as a liquid solution (50 ml) or aerated by a hand pumping device (foaming soap container) to create a foaming solution (approximately 25 ml) that was applied to completely cover the virus inoculated stainless steel coupons.
  • the coupon or grape was transferred to a 50 ml conical tube containing 10 ml of complete DMEM containing 20% FBS and gently rocked for 5 seconds to neutralize the sanitizer.
  • the stainless steel coupon or grape was then transferred to a 50 ml conical tube containing 10 ml of 0.1 M PBS with 1 M NaCI and vigorously vortexed to elute viruses from the stainless steel coupon.
  • a non-inoculated stainless steel coupon and uninoculated grape was also processed and served as a negative control.
  • Neutralization controls where virus was added to 50 ml conical tubes containing the elution buffer after sanitizer neutralization, were also included.
  • FBS proteinaceous material
  • MNV was not inactivated at 1 min, but was reduced by 3.41 log after the 5 min treatment with 5% levulinic acid plus 2% sodium dodecyl sulfate. MNV removal from the grape surface by water was only 2.11 log after 5 min, as shown in Fig. 9.
  • Bacteria cultivation and plaque assay Five serovars of Salmonella enterica, (Typhimurium, Enteritidis, Gaminara, Agona, and Montevideo) were inoculated separately in 10 ml. of tryptic soy broth (Difco, Franklin Lakes, NJ). Cultures were incubated at 37 0 C and transferred twice to fresh vials of TSB, 24 hours apart. For each strain, 5 ml of inoculated broth was transferred to a conical 50 ml tube and centrifuged at 8,000 x g at 4 0 C for 10 minutes. The supernatant was removed and replaced with 25 ml of 0.1 M phosphate buffered saline before the tube was vortexed for 1 minute to resuspend the pellet.
  • Coupons were placed on an electronic scale, sterilized by exposure to UV light for 15 minutes. For each repetition, 1 or 5 wiping motions was made over the inoculated area using a gloved hand at 50 ⁇ 5 g pressure. All wipes were cut into 1.5x1.5 cm squares and autoclaved at 121 0 C and 16 psi for 30 minutes before use.
  • Wipes tested included water filters containing nano-alumina fibers
  • NANOCERAM. RTM Sanford, FL
  • charge modified glass fibers VIROSORB.RTM 1 MDS, Cuno, Meriden, CT
  • cellulose filters Millipore, Billerica, MA and (Whatman, Kent, UK).
  • each wipe was immersed into a 50 ml conical tube containing the desired sanitizer (2% levulinic acid plus 1% sodium dodecyl sulfate, 5% levulinic acid plus 2% sodium dodecyl sulfate, 5% levulinic acid plus 1 % sodium dodecyl sulfate or 5% levulinic acid plus 2% sodium dodecyl sulfate) or water, removed with a pipet tip and gently squeezed by pressing the wipe against the side of the tube with the tip to remove excess moisture.
  • the desired sanitizer 2% levulinic acid plus 1% sodium dodecyl sulfate, 5% levulinic acid plus 2% sodium dodecyl sulfate, 5% levulinic acid plus 1 % sodium dodecyl sulfate or 5% levulinic acid plus 2% sodium dodecyl sulfate
  • Homogenate was plated in 1 :10 dilutions on TSA and XLT4 media as previously described. Duplicate cell culture plates for all pathogens were averaged and used to calculate titer after treatment. For a positive control, an inoculated coupon or latex glove finger was dried and pathogen was recovered without any wipe treatment. Negative controls, stainless steel without inoculation, were performed in duplicate and included with each experimental trial. Log reduction of pathogen was calculated as follows: log value of pfu recovered from wiped coupon or glove subtracted from the log value recovered from positive control.
  • NANOCERAM NANOCERAM.
  • RTM and 1MDS vs. Whatman wipes soaked in water of Lev plus sodium dodecyl sulfate showed no significant difference in log reduction (p > 0.05). Comparison of 1 or 5 wiping motions yielded a significant difference using Whatman wipes with water for both 1 and 5 swiping motions (p ⁇ 0.02).

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Abstract

La présente invention porte sur des compositions comprenant un agent tensio-actif, et un acide tel que, mais sans y être limité, l'acide lévulinique, qui ont ensemble un effet synergique pour réduire la viabilité d'une population de virus par comparaison à l'efficacité des composés individuels. Cette synergie permet la formulation de compositions dans lesquelles les agents actifs (comprenant un acide et un agent tensio-actif) sont présents à des concentrations efficaces pour inactiver des virus sur des surfaces, comprenant la peau humaine. Les compositions virucides décrites ici sont efficaces sans endommager la surface à laquelle elles peuvent être appliquées, ou sans même altérer les propriétés organoleptiques d'une substance alimentaire traitée. Les compositions virucides et lingettes contenant de telles compositions sont appropriées pour désinfecter toute surface suspectée avoir une charge virale sur celle-ci, ou lorsqu'il est souhaitable d'assurer qu'une charge virale soit aussi faible que possible.
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