Classifications

• • A—HUMAN NECESSITIES
  • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
  • A01P—BIOCIDAL, PEST REPELLANT, PEST ATTRACTANT OR PLANT GROWTH REGULATORY ACTIVITY OF CHEMICAL COMPOUNDS OR PREPARATIONS
  • A01P1/00—Disinfectants; Antimicrobial compounds or mixtures thereof

Definitions

• the present invention pertains to antimicrobial compositions. More particularly, the present invention is directed toward antimicrobial compositions that possess yeasticidal functionality.
• Antimicrobial agents are generally used to kill pathogenic microorganisms that create a risk of infection for humans or animals. Antimicrobial agents are used especially in veterinary applications to control and/or prevent hoof diseases, mastitis, or topical infections. Prevention of mastitis is a major goal of the dairy industry, where the disease may result from the contact of the bovine or ovine mammary gland with pathogenic microorganisms. Mastitis is a potentially serious infection, where severe cases can cause the death of a dairy animal.
• teat dips that are generally administered to the animal’s teat by dipping, spraying, or foaming the teat prior to and after milking.
• teat disinfectants possess yeasticidal functionality and must be effective pre-milking at short contact times.
• Traditional oxidative germicides employing iodine and chlorine dioxide as the primary antimicrobial agents exhibit yeasticidal functionality.
• these compositions are not desirable in some markets because of residue concerns for iodine and chlorate. Teat dip compositions that comprise less concerning active ingredients from a milk quality perspective, such as those comprising one or more organic acids as the antimicrobial active(s) do not exhibit yeasticidal efficacy.
• antimicrobial compositions have been developed that offer broad spectrum in vitro protection against a number of mastitis-causing pathogens. However, these same antimicrobial compositions can cause undesirable irritation of the animal’s skin making the compositions ill suited for in vivo use.
• an antimicrobial composition that includes salicylic acid, glycolic acid, and at least one anionic surfactant.
• an antimicrobial composition that comprises salicylic acid, glycolic acid, and at least one alkyl sulfate surfactant.
• the composition comprises at least one alkyl sulfate surfactant comprising sodium lauryl sulfate.
• an antimicrobial composition that comprises salicylic acid, glycolic acid, and at least one anionic surfactant comprising an alkyl sulfate.
• the antimicrobial composition exhibits at least a four-log reduction in C. albicans when tested in accordance with EN 1657 at a one-minute contact time, at 30°C, and in the presence of 10 g/L bovine albumin and 10 g/L yeast extract as an interfering substance (high soil condition), or with 3 g/L bovine albumin as interfering substance (low soil condition).
• an antimicrobial composition that comprises salicylic acid, glycolic acid, at least one anionic surfactant comprising an alkyl sulfate, and optionally one or more of the following components: a freezing point depressant compound, magnesium oxide, at least one additional anionic surfactant selected from the group consisting of a-olefin sulfonates and alkyl sulfonates, and at least one non-ionic surfactant comprising an alcohol ethoxylate.
• an antimicrobial composition that comprises salicylic acid, glycolic acid, and at least one anionic surfactant.
• the composition is storage stable for at least one month at 4°C.
• an antimicrobial composition that comprises from 0.15% to 0.6% by weight of salicylic acid, from 0.5% to 10% by weight of glycolic acid, from 0.3% to 1 % of at least one anionic surfactant, and optionally from 0.5% to 10% of a freezing point depressant compound and/or from 0.02% to 1 % of magnesium oxide.
• a method for controlling or preventing bovine mastitis includes contacting the teats of a cow with a teat dip, which includes salicylic acid, glycolic acid, and an anionic surfactant, preferably an alkyl sulfate surfactant, and even more preferably sodium lauryl sulfate.
• a teat dip which includes salicylic acid, glycolic acid, and an anionic surfactant, preferably an alkyl sulfate surfactant, and even more preferably sodium lauryl sulfate.
• a method for controlling or preventing bovine mastitis comprising contacting the teats of a cow with a teat dip comprising an antimicrobial composition as described herein.
• an antimicrobial teat dip composition for use in the control or prevention of bovine mastitis when contacted with the teats of a cow.
• the composition comprises salicylic acid, glycolic acid, and at least one anionic surfactant.
• the antimicrobial composition exhibits at least a four-log reduction in C. albicans when tested in accordance with EN 1657 at a one-minute contact time, at 30°C, and in the presence of 10 g/L bovine albumin and 10 g/L yeast extract as an interfering substance (high soil condition), or with 3 g/L bovine albumin as interfering substance (low soil condition).
• an antimicrobial teat dip composition for use in the control or prevention of bovine mastitis when contacted with the teats of a cow, wherein the composition comprises an antimicrobial composition as described herein.
• compositions that exhibit fungicidal efficacy, that include salicylic acid, glycolic acid, and one or more anionic surfactants.
• salicylic acid and glycolic acid are the only organic acids present in the compositions.
• organic acids that possess antimicrobial characteristics may also be included such as lactic acid, tartaric acid, citric acid, ascorbic acid, maleic acid, succinic acid, mandelic acid, dodecylbenzenesulfonic acid, propionic acid, gluconic acid, malic acid, benzoic acid, aspartic acid, acetic acid, oxalic acid, glutamic acid, adipic acid, hexanoic acid, octanoic acid, nonanoic acid, decanoic acid, and undecanoic acid.
• salicylic acid and glycolic acid make up the majority of all organic acids present in the composition.
• inorganic acids having pK a characteristics approximating those of organic acids may also be used, such as, sulfamic acid.
• Anionic surfactants suitable for use in the present invention include, but are not limited to, alkyl sulfonates, secondary alkane sulfonates, alkyl sulfates, alkyl ether sulfates, aryl sulfonates, aryl sulfates, alkylaryl sulfonates, alkylaryl sulfates and alkyl ether sulfonates, and the corresponding acids thereof.
• a non-limiting list of specific anionic surfactants suitable for use in the present invention includes alkali lauryl sulfates, e.g., sodium lauryl sulfate (SLS), alkali dodecylbenzenesulfonates, alkali octane sulfonates, e.g., sodium octane sulfonate (SOS), alkali secondary alkane sulfonates, alkali lauryl ether sulfates and ammonium salts thereof.
• SLS sodium lauryl sulfate
• SOS sodium octane sulfonate
• alkali secondary alkane sulfonates alkali lauryl ether sulfates and ammonium salts thereof.
• Additional anionic surfactants may include: a linear alkyl benzene sulfonate, an alkyl a-sulfomethyl ester, an a-olefin sulfonate, an alcohol ether sulfate, an alkylsulfo succinate, and a dialkylsulfo succinate.
• additional anionic surfactants are linear C10-C16 alkylbenzene sulfonic acid, linear C10-C16 alkylbenzene sulfonate or alkali metal, alkaline earth metal, amine and ammonium salts thereof, e.g., sodium dodecylbenzene sulfonate, sodium C14- C a-olefin sulfonate, sodium methyl a-sulfomethyl ester and disodium methyl a-sulfo fatty acid salts.
• the antimicrobial compositions of the present invention may include a mixture of any of the above listed anionic surfactants.
• anionic surfactants disclosed hereto may be in acid form, or in the form of an alkali metal, an alkaline earth metal, an amine, or an ammonium salt.
• compositions according to the present invention do not comprise an a-olefin sulfonate as the only anionic surfactant.
• SLS comprises an anionic surfactant
• a combination of at least two, and preferably three, anionic surfactants are used.
• these preferred compositions comprise at least two of sodium a-olefin sulfonate, sodium alkane sulfonate, and sodium lauryl sulfate.
• the sodium alkane sulfonate is the predominant anionic surfactant followed by sodium lauryl sulfate and then sodium a-olefin sulfonate; however, this need not always be the case.
• the weight ratio of sodium alkane sulfonate to sodium a-olefin sulfonate is from 2:1 to 4:1 , and preferably about 3:1.
• the weight ratio of sodium alkane sulfonate to sodium lauryl sulfate is 1.1 :1 to 3:1 , and preferably about 1.5:1. In certain embodiments, the weight ratio of sodium a-olefin sulfonate to sodium lauryl sulfate is 1 :1 to 1 :3, and preferably about 1 :2.
• compositions according to the present invention may optionally, but preferably, comprise one or more nonionic surfactants.
• Nonionic surfactants suitable for use in the present invention include, but are not limited to, alkyl polyglucosides, alkyl ethoxylated alcohols, alkyl propoxylated alcohols, ethoxylated- propoxylated alcohols, sorbitans, sorbitan esters, alkanol amides, ethyleneoxidepropyleneoxide block copolymers, and mixtures thereof.
• a non-limiting list of specific nonionic surfactants includes a C9-C11 alcohol with an average of approximately 8 moles of ethylene oxide per mole of alcohol (Neodol® 91 -8 from Shell Chemicals), a Cs-C-is alcohol with odd or even number carbon chain, with an average of 6 to 18 moles of ethylene oxide per mole of alcohol, alkyl polyglucosides (e.g., TritonTM BG10 from Dow Corp, or Lutensol® GD 70 from BASF Corp.), branched secondary alcohol ethoxylates (e.g., TERGITOLTM TMN Series from Dow Corp.), ethylene oxide / propylene oxide copolymers (e.g., TERGITOLTM L Series from Dow Corp.), secondary alcohol ethoxylates (e.g., ECOSURFTM LF-20 or TERGITOLTM 15-S Series from Dow Corp.), polyether polyols (e.g., TERGITOLTM L-61
• nonylphenol ethoxylates e.g., TERGITOLTM NP Series from Dow Corp.
• octylphenol ethoxylates e.g., TRITONTM X Series from Dow Corp
• seed oil surfactants e.g., ECOSURFTM SA surfactants from Dow Corp.
• alkyl polysaccharides e.g., ALKADET® series from Huntsman Chemicals
• alkylamine ethoxylates e.g., SURFONIC® T series from Huntsman Chemicals
• amine oxides e.g., EMPIGEN® 0 series from Huntsman Chemicals
• block copolymers e.g., EMPILAN® KCMP series from Huntsman Chemicals
• castor oil ethoxylates e.g., SURFONIC® CO series from Huntsman Chemicals
• ceto-oleyl alcohol ethoxylates e.g., EMPILAN
• the nonionic surfactant includes an alcohol ethoxylate, such as Neodol® 91 -8 or Surfonic® L12-8.
• an alcohol ethoxylate is the only nonionic surfactant present.
• the bactericidal activity of the compositions of the present invention may be due to the presence of a specific combination of a glycolic acid and one or more anionic surfactants, and, optionally a nonionic surfactant.
• the yeasticidal activity of the compositions may be due to the presence of salicylic acid, especially when combined with glycolic acid and the one or more anionic surfactants.
• the antimicrobial activity (bactericidal and yeasticidal activity) of the compositions of the present invention may be due to the presence of a specific combination of glycolic acid, salicylic acid, and SLS.
• these compositions may further comprise one or more of an alcohol ethoxylate surfactant, an a-olefin sulfonate, and an alkane sulfonate, and preferably all three.
• the glycolic acid may be present in an amount of at least 0.05, 0.1 , 0.5, 0.75, 0.9, 1 , 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, or 6 wt. %. In the same or alternative embodiments, the glycolic acid may be present in an amount of not more than 10, 9.5, 9, 8.5, 8, 7.5, 7, 6.5, 6, 5.5, 5, 4.5, or 4 wt. %. For example, in one or more embodiments, the glycolic acid may be present in an amount of from 0.5-10 wt. %, 0.75-5 wt. %, or 0.9-3.5 wt. %.
• the salicylic acid may be present in an amount of at least 0.1 , 0.15, 0.2, 0.25, 0.3, 0.35, 0.4, or 0.5 wt. %. In the same or alternative embodiments, the salicylic acid may be present in an amount of not more than 1 , 0.8, 0.75, 0.7, 0.65, 0.6, 0.55, 0.50, 0.45, or 0.4 wt. %. For example, in one or more embodiments, the salicylic acid may be present in an amount of from 0.15-0.6 wt. %, 0.2- 0.55 wt. %, or 0.25-0.5 wt. %.
• one or more anionic surfactants may each be present in an amount of at least 0.01 , 0.05, 0.1 , 0.2, 0.5, 1 ,1.5, or 2 wt. %.
• one or more anionic surfactants may be present in an amount of not more than 5, 4.5, 4, 3.5, 3, 2.5, 2, 1.5, or 1 wt. %.
• one or more anionic surfactants may each be present in an amount of from 0.01 to 5 wt. %, 0.05 to 3 wt. %, or 0.1 to 2 wt. %.
• the nonionic surfactant may be present in an amount of at least 0.001 , 0.005, 0.01 , 0.05, 0.1 , 0.2, 0.3, 0.4, 0.5, 1 , 2, or 2.5 wt. %. In the same or alternative embodiments, the nonionic surfactant may be present in an amount of not more than 10, 7.5, 6.5, 5.5, 5, 4.5, 4, 3.5, 3, 2.5, 2, 1.5, 1 , 0.5, 0.4, or 0.3 wt. %. For example, in one or more embodiments, the nonionic surfactant may be present in an amount of from 0.01 -10 wt.%, 0.05-5 wt. %, or 0.1 -1 wt.%
• the total concentration of anionic and nonionic surfactants is at least 0.05, 0.1 , 0.5, 0.75, 1 , 1 .25, 1.5, 1 .75, or 2 wt. %. In the same or alternative embodiments, the total concentration of anionic and nonionic surfactants is not more than 10, 7.5, 5, 3, or 2.5 wt. %. For example, in one or more embodiments, the total concentration of anionic and nonionic surfactants is from 0.05 to 10 wt. %, 0.1 to 5 wt. %, or 0.5 to 3 wt. %.
• compositions of the present invention comprise at least two anionic surfactants and a nonionic surfactant.
• weight ratio between the total amount of organic acid and the total anionic surfactant concentration is from 5:1 to 1 :2, from 3:1 to 1 :1 , or from 2:1 to 1.25:1.
• the composition is aqueous comprising water in an amount ranging from at least 50, 60, 70, or 75 wt. %, and/or not more than 99, 97, 95, or 90 wt. %.
• water may be present in amount ranging from 60 to 90 wt. %, 65 to 85 wt. %, or 70 to 80 wt. %.
• solvents includes water, an alcohol, propylene glycol, glycol ethers and/or alcohols. In certain embodiments, a mixture of two or more of the aforementioned solvents may be used.
• the antimicrobial compositions of the present invention may include one or more additives, such as a buffering agent, an emollient, a humectant, a preservative, a barrier forming agent, a surfactant or wetting agent, a foaming agent, a viscosity control agent, a colorant, an opacifying agent, a skin conditioning agent, and an additional antimicrobial agent.
• additives such as a buffering agent, an emollient, a humectant, a preservative, a barrier forming agent, a surfactant or wetting agent, a foaming agent, a viscosity control agent, a colorant, an opacifying agent, a skin conditioning agent, and an additional antimicrobial agent.
• Barrier and film forming agents can be used in compositions formulated as teat dips so that the composition remains in contact with the teat between milking cycles.
• Barrier and film forming agents coat the teat skin and, optionally, the udder.
• Barrier agents may form a plug at the end of the open teat canal.
• Typical barrier and film forming agents include thick creams or emollients (made with viscosity control agents), films, polymers, latex and the like.
• Some nonionic surfactants may help further enhance the barrier properties of a composition, in addition to contributing to surface wetting. Examples of such surfactants may include, without limitation, polyoxyethylenepolyoxypropylene glycol (marketed as Pluronic® F108).
• Suitable barrier forming agents include, for example, latex, arabinoxylanes, glucomannanes, guar gum, johannistree gums, cellulose, methyl cellulose, ethyl cellulose, hydroxyethyl cellulose, hydroxymethyl cellulose, carboxyethyl cellulose, carboxymethyl cellulose, starch, hydroxyethyl starch, gum arabic, curdlan, pullulan, dextran, maltodextran, polysulfonic acid, polyacryl amide, high molecular weight polyacrylate, high molecular weight cross-linked polyacrylate, carbomer, sodium alginate, sodium alginate cross-linked with calcium salt, xanthan gum, poly(vinyl alcohol) (PVA) and poly(N-vinylpyrrolidon
• barrier-forming agents include xanthan gum, carboxymethyl cellulose, sodium alginate, sodium alginate cross- linked with calcium salt, PVA, hydroxyethyl cellulose, PVP, and (2,5-dioxo-4- imidazolidinyl)-urea (Allantoin).
• the compositions of the present invention may include a modified polysaccharide as a barrier film-forming agent to form a long-lasting persistent, continuous, uniform barrier film when applied to the skin.
• a modified polysaccharide as a barrier film-forming agent to form a long-lasting persistent, continuous, uniform barrier film when applied to the skin.
• Such compositions have particular utility as barrier teat dips that are used prophylactically against mastitis.
• Such compositions may include relatively low molecular weight polysaccharides, for example, as may be derived specifically from hydrolyzed starch.
• Such compositions that are capable of forming a long-lasting, persistent, continuous, uniform barrier film may contain from about 0.1 % to about 20% by weight of modified or hydrolyzed polysaccharide material for use as the barrier forming agent.
• the polysaccharide material may have a majority polysaccharide component as starch, modified starch, hydrolyzed starch, a starch derivative, and combinations thereof.
• the majority polysaccharide components may have overall or average Dextrose Equivalence (DE) value ranging from 2 to 50, and this value more preferably ranges from 3 to 27.
• DE Dextrose Equivalence
• the term “majority polysaccharide component” is used to describe a majority weight percentage of all polysaccharides in the composition, i.e. , more than 50% of all polysaccharides in the composition.
• a foaming agent may be used in the disclosed antimicrobial compositions.
• a foaming agent aerates a liquid composition to produce a foam that may increase surface area of the composition and improve contact with the surface to be treated (e.g., an animal hoof or a teat).
• a foaming agent is in the form of a compressed gas, or a material that will decompose to release gas under certain conditions. Suitable gases include but are not limited to nitrogen, argon, air, carbon dioxide, helium and mixtures thereof.
• solid carbon dioxide (dry ice), liquid nitrogen, hydrogen peroxide and other substances that release gas via a change in state or through decomposition are contemplated for use with the present compositions.
• a high foaming surfactant such as sodium lauryl sulfate, dodecylbenzene sulfonic acid, sodium alkylaryl polyether sulfate, sodium lauryl ether sulfate, sodium decyl sulfate, cocamine oxide, or C12-C14 whole coconut amido betaines
• the foam may be produced when agitation in the form of a compressed gas is mixed with the solution either by bubbling the gas into the solution or spraying the solution or solution-gas mixture through spray equipment.
• foam may also be generated by the mechanical action, or by other mechanical means that mix atmospheric air with the composition.
• Surfactants are well known for foaming and are widely used as foaming agents in hand soap and manual/hand dishwashing detergents and may also be used as foaming agents in applications where foaming boosts the performance and increases the contact time of the composition to particular substrates.
• anionic surfactants can be chosen from a linear alkyl benzene sulfonic acid, a linear alkyl benzene sulfonate, an alkyl a-sulfomethyl ester, an a-olefin sulfonate, an alcohol ether sulfate, an alkyl sulfate, an alkylsulfo succinate, a dialkylsulfo succinate, and alkali metal, alkaline earth metal, amine and ammonium salts thereof.
• linear C10-C16 alkyl benzene sulfonic acid linear C10-C16 alkyl benzene sulfonate or alkali metal, alkaline earth metal, amine and ammonium salts thereof, e.g., sodium dodecylbenzene sulfonate, sodium C14-C16 a-olefin sulfonate, sodium methyl a-sulfomethyl ester and disodium methyl a-sulfo fatty acid salts.
• Suitable nonionic surfactants may be chosen from an alkyl polyglucoside, an alkyl ethoxylated alcohol, an alkyl propoxylated alcohol, an ethoxylatedpropoxylated alcohol, sorbitan, sorbitan ester, and an alkanol amide.
• Amphoteric surfactants can be chosen from alkyl betaines and alkyl amphoacetates.
• Suitable betaines include cocoamidopropyl betaine, and suitable amphoacetates include sodium cocoamphoacetate, sodium lauroamphoacetate and sodium cocoamphodiacetate.
• Alkyl amine oxides based on C12-C14 alkyl chain length feedstock such as those derived from coconut oil, palm kernel oil may also be suitable foaming agents.
• viscosity control agents may be added to formulate the antimicrobial compositions according to an intended environment of use.
• This type of viscous product especially one having a suitable thixotropic, pseudoplastic or viscoelastic gel strength, minimizes dripping of the product to avoid wastage and is particularly advantageous in teat dip compositions.
• Teat dip compositions may benefit from a preferred dynamic viscosity ranging from 1 cPs to 3000 cPs.
• Other applications including hard surface disinfectants have a preferred dynamic viscosity ranging from about 1 cPs to 300 cPs.
• the amount of viscosity control agents may be substantially reduced or even eliminated in other compositions, such as surface or floor disinfectants where easy cleanup is desired.
• An intermediate or medium viscosity composition may be useful in a hand cleaner or personal care product. It is within the scope of the present invention for the antimicrobial compositions to be formulated for a wide variety of applications by altering the amount of viscosity control agents.
• the viscosity referred to throughout this application is Brookfield viscosity measured in cPs by a Brookfield LV viscometer at ambient temperature (25° C.) with either spindle # 1 @ 60 - 100 rpm or spindle # 2 @ 15 to 30 rpm.
• a thickener may be added to achieve a viscosity range of from 50 cPs to 10000 cPs, or from 100 cPs to 4000 cPs.
• Suitable viscosity control agents include hemicellulose, for example arabinoxylanes and glucomannanes; plant gum materials, for example guar gum and johannistree gums; cellulose and derivatives thereof, for example methyl cellulose, ethyl cellulose, hydroxypropyl cellulose, hydroxyethyl cellulose or carboxymethyl cellulose; starch and starch derivatives, for example hydroxyethyl starch or cross linked starch; microbial polysaccharides, for example xanthan gum, sea weed polysaccharides, for example sodium alginate, carrageenan, curdlan, pullulan or dextran, dextran sulfate, whey, gelatin, chitosan, chitosan derivatives, polysulfonic acids and their salts, polyacrylamide, and glycerol.
• plant gum materials for example guar gum and johannistree gums
• cellulose and derivatives thereof for example methyl
• Preferred viscosity controlling agents are xantham gum, different types of cellulose and derivatives thereof, particularly hydroxyalkyl cellulose, methyl cellulose, and glycerol.
• high molecular weight (MW>1 ,000,000) crosslinked polyacrylic acid type thickening agents may be used, such as those sold by B.F. Goodrich (now Lubrizol) under their Carbopol® trademark, especially Carbopol® 941 , which is the most ion-insensitive of this class of polymers, Carbopol® 940, and Carbopol® 934.
• the Carbopol® resins also known as “Carbomer”, are reported in U.S. Pat. No.
• Carbopol® 941 has a molecular weight of about 1 ,250,000
• Carbopol® 940 has a molecular weight of approximately 4,000,000
• Carbopol® 934 has a molecular weight of approximately 3,000,000.
• the Carbopol® resins are cross-linked with polyalkenyl polyether, e.g. about 1 % of a polyallyl ether of sucrose having an average of about 5.8 alkyl groups for each molecule of sucrose. Further detailed information on the Carbopol® resins is available from B.F. Goodrich (Lubrizol), see for example, the B. F.
• the viscosity control agent may include carboxymethyl cellulose, sodium alginate, sodium alginate cross-linked with calcium salt, polysulfonic acids and their salts, polyacrylamide, polyvinyl alcohol (PVA), hydroxyethyl cellulose and poly-N-vinylpyrrolidone) (PVP).
• a buffering agent, or a pH adjusting agent may be added to the disclosed compositions.
• a composition pH value may be selectively adjusted by the addition of acidic or basic ingredients. Generally, an acidic pH is preferred. Suitable acids for use as pH adjusting agents may include, for example, citric acid, formic acid, acetic acid, lactic acid, phosphoric acid, phosphorous acid, sulfamic acid, nitric acid, nitrous acid and hydrochloric acid. It will be recognized by those skilled in the art that the organic acid, e.g., glycolic acid, selected as the antimicrobial organic acid will also influence pH, and thus, have an adjusting effect as discussed in this paragraph.
• the organic acid e.g., glycolic acid
• Mineral acids may be used to drastically lower the pH.
• the pH may be raised or made more alkaline by addition of an alkaline agent such as sodium hydroxide, potassium hydroxide, sodium carbonate, sodium bicarbonate, monosodium acid diphosphonate or combinations thereof.
• Traditional acid buffering agents such as citric acid, lactic acid, and phosphoric acid may also be used to maintain a desired pH.
• the pH value of the composition may be adjusted by the addition of acidic or basic or buffering materials.
• the physical property of pH may be adjusted by acid or base addition and is broadly preferred in the range of from about 2.0 to about 8.0 for use in teat dip compositions and other compositions that are intended to contact the skin. More preferred ranges include about 2.0 to about 7.5, about 2.2 to about 6.0, and about 2.5 to about 4.5.
• Hard surface and commercial disinfectants may be provided with lower pH values, such as about 2.0 or about 1 .0.
• the inventive compositions may include a wetting agent.
• Wetting agents or surface-active agents are also known as surfactants. Typical wetting agents are used to wet the surface of application, reduce surface tension of the surface of application so that the product can penetrate easily on the surface and remove unwanted soil.
• the wetting agents or surfactants of the disclosed compositions may increase overall detergency of the formula, solubilize or emulsify some of the organic ingredients that otherwise would not dissolve or emulsify, and facilitate penetration of active ingredients deep onto the surface of the intended application surfaces, such as teat skin.
• Suitable surfactants used as wetting agents in the present invention include anionic, cationic, nonionic, zwitterionic, and amphoteric surfactants.
• Wetting agents and surfactants used in the inventive applications can be high foaming, low foaming, and non-foaming type.
• Suitable anionic surfactants can be chosen from a linear alkyl benzene sulfonic acid, a linear alkyl benzene sulfonate, an alkyl a-sulfomethyl ester, an a-olefin sulfonate, an alcohol ether sulfate, an alkyl sulfate, an alkylsulfo succinate, a dialkylsulfo succinate, and alkali metal, alkaline earth metal, amine, and ammonium salts thereof.
• a linear C10-C16 alkyl benzene sulfonic acid or alkali metal, alkaline earth metal, amine, and ammonium salts thereof e.g., sodium dodecylbenzene sulfonate; sodium C14-C16 a-olefin sulfonate; sodium methyl a- sulfomethyl ester; and disodium methyl a-sulfo fatty acid salt.
• Suitable nonionic surfactants can be chosen from an alkyl polyglucoside, an alkyl ethoxylated alcohol, an alkyl propoxylated alcohol, an ethoxylatedpropoxylated alcohol, sorbitan, sorbitan ester, an alkanol amide.
• Pluronic® poloxamers commercialized by BASF Chemical Co.
• Amphoteric surfactants can be chosen from alkyl betaines and alkyl amphoacetates.
• Suitable betaines include cocoamidopropyl betaine
• suitable amphoacetates include sodium cocoamphoacetate, sodium lauroamphoacetate and sodium cocoamphodiacetate.
• An opacifying agent or dye may be optionally included in the present compositions.
• color on a teat tells a farmer that a particular cow has been treated.
• FD&C Certified (food grade) dyes be used.
• FD&C dyes There are many FD&C dyes available, such as FD&C Red #40 (E129), FD&C Yellow #6 (E110), FD&C Yellow #5 (E102), and FD&C Blue #1 (E133).
• Dyes used either alone or in combination are preferred.
• D&C Orange #4 can also be used. Titanium dioxide (TiO2) is widely used as an opacifier and can also be used in combination with various colorants.
• a preservative may be included in the inventive compositions.
• preservatives includes ethylenediaminetetraacetic acid (EDTA) and its alkali salts, paraban, methyl paraban, ethyl paraban, glutaraldehyde, benzyl alcohol, and low molecular weight alcohols having a carbon number less than five.
• EDTA ethylenediaminetetraacetic acid
• more than one type of preservative may be utilized.
• chelating agents such as EDTA, function as preservatives by sequestering or removing metal ions from hard water. The metal ions, if not removed from the composition, serve as reaction sites for enzymes within the bacteria; the metalloenzyme reactions produce energy for bacterial cell replication.
• one or more skin conditioning agents may be included in the inventive compositions.
• Skin conditioning agents may provide extra protection for human or animal skin prior to or subsequent to being exposed to adverse conditions.
• skin conditioning agents may include moisturizers, such as glycerin, sorbitol, propylene glycol, D-Panthenol, Poly Ethylene Glycol (PEG) 200-10,000, Poly Ethylene Glycol Esters, Acyl Lactylates, Polyquaternium-7, Glycerol Cocoate/Laurate, PEG-7 Glycerol Cocoate, Stearic Acid, Hydrolyzed Silk Peptide, Silk Protein, Aloe Vera Gel, Guar Hydroxypropyltrimonium Chloride, Alkyl Poly Glucoside/Glyceryl Luarate, shea butter and coco butter; sunscreen agents, such as titanium dioxide, zinc oxide, octyl methoxycinnamate (OMC), 4-methylbenzylidene camphor (4-MBC),
• OMC oct
• the antimicrobial compositions of the present invention may be used in combination with traditional antimicrobial agents to achieve effective kill rates at lower concentrations of traditional antimicrobial agents than those typically used when the traditional antimicrobial agents provide the sole source of antimicrobial activity.
• Traditional antimicrobial agents include iodophors, quaternary ammonium compounds, hypochlorite releasing compounds (e.g. alkali hypochlorite, hypochlorous acid), oxidizing compounds (e.g. peracids and hypochlorite), carboxylic acids (e.g. heptanoic, octanoic, nonanoic, decanoic, undecanoic acids), acid anionics (e.g.
• Phenolic antimicrobial agents may be chosen from 2,4,4'-trichloro-2"-hydroxydiphenylether, which is known commercially as triclosan and may be purchased from Ciba Specialty Chemicals as IRGASANTM and IRGASAN DP 300TM.
• Another such antimicrobial agent is 4-chloro- 3,5-dimethyl phenol, which is also known as PCMX and is commercially available as NIPACIDE PX and NIPACIDE PX-P.
• Other traditional germicides include formaldehyde releasing compounds such as glutaraldehyde and 2-bromo-2-nitro-1 ,3-propanediol (Bronopol), polyhexamethyl biguanide (CAS 32289-58-0), guanidine salts such as polyhexamethylene guanidine hydrochloride (CAS 57028-96-3), polyhexamethylene guanidine hydrophosphate (89697-78-9), and poly[2-(2-ethoxy)-ethoxyethyl]-guanidinium chloride (CAS 374572-91 -5) and mixtures thereof.
• the disclosed antimicrobial compositions may be used in combination with traditional antimicrobial agents, such as copper sulfate, zinc sulfate, sulfamethazine, quaternary ammonium compounds, hydrogen peroxide and/or peracetic acid, for example, to achieve an effective kill at lower concentrations of traditional antimicrobial agents.
• traditional antimicrobial agents such as copper sulfate, zinc sulfate, sulfamethazine, quaternary ammonium compounds, hydrogen peroxide and/or peracetic acid, for example, to achieve an effective kill at lower concentrations of traditional antimicrobial agents.
• the antimicrobial compositions of the present invention do not include hydrogen peroxide (or hydrogen peroxide generating compounds), chlorine dioxide (or chlorine dioxide generating compounds), chlorhexidine, iodophors, and/or iodine. In one or more embodiments, the antimicrobial compositions of the present invention are iodine free. In certain embodiments, the antimicrobial compositions of the present invention are hydrogen peroxide free. In one or more embodiments, the antimicrobial compositions of the present invention are chlorhexidine free. In certain embodiments, the antimicrobial compositions of the present invention are chlorine dioxide free. In certain embodiments, the antimicrobial compositions are lactic acid free.
• the antimicrobial compositions of the present invention may provide a substantial reduction in Gram positive and Gram negative bacteria, as well other numerous classes of microbes.
• the reduction may be at least a three, four, five, or six log reduction in Gram positive and/or Gram negative bacteria.
• the antimicrobial compositions may exhibit a substantially complete kill that is at least a five log (99.999%) reduction in bacterial populations.
• the antimicrobial compositions may provide any of the foregoing log reductions within one minute, 45 seconds, or 30 seconds of contact time when tested according to EN 1656, at 30°C, as described in the Examples below.
• the antimicrobial compositions of the present invention may provide a substantial reduction in fungi, especially yeast.
• the reduction may be at least a two, three, or four log reduction in fungi, and yeast in particular.
• the antimicrobial compositions may exhibit a substantially complete kill that is at least a four log reduction in yeast populations
• the antimicrobial compositions may provide any of the foregoing log reductions within two minutes, one minute, or 30 seconds of contact time when tested according to EN 1657, at 30°C, as described in the Examples below.
• the antimicrobial compositions of the present invention may comprise components that assist in providing low temperature stability for the compositions.
• Preferred cold temperature-stabilizing components include, but are not limited to, propylene glycol and magnesium oxide.
• the compositions are storage stable for at least one week, at least one month, at least three months, or at least six months at 4°C.
• storage stable refers to the characteristic of the compositions that various components present within the composition do not separate out from the other components following formulation and until usage, or until at least passage of a specified period of time.
• Compositions according to certain embodiments of the present invention are formulated so that these components that may not be particularly highly water soluble, or that may interact with other components to precipitate out, remain suspended and/or in solution for the indicated periods of time under low temperature storage conditions.
• the antimicrobial compositions may be used for prophylactic treatment of a dairy animal's teats to provide a long lasting persistent protective germicidal barrier film that demonstrates persistence between milkings, and is controllably reproducible to yield a continuous, uniform persistent barrier.
• This treatment process may include milking the animal, coating the teats with the composition after milking, allowing the composition to dry and so also form a layer of persistent barrier film on the teats.
• the compositions of the present invention may be used as a germicide on an animal’s teats but may not form a long-lasting persistent barrier film on the teats.
• the composition may be applied topically by painting, foaming, dipping or spraying.
• use of the composition is not limited to use against mastitis, and the composition may be used generally to treat or protect against any infectious skin condition.
• the antimicrobial compositions may be used to clean and/or disinfect a dairy animal’s teats prior to milking in order to avoid contamination of the milk produced from the animal with various bacteria and yeasts.
• the antimicrobial compositions may also be applied post-milking, in a barrier or non-barrier form, in order to clean and/or disinfect the dairy animal’s teats thereby lessening the animal’s chances of developing mastitis.
• the antimicrobial compositions of the present invention may be used, for example, in any manner where application of antimicrobial agents is desired.
• the antimicrobial compositions of the present invention may be used as a hand sanitizer, a skin cleanser, a surgical scrub, a wound care agent, a disinfectant, a mouthwash, a bath/shower gel, a hard surface sanitizer and the like.
• Preferred compositions for skin applications have a pH of about 2.0 to about 8.0 and provide a substantial reduction, e.g., greater than a five- log reduction (99.999%), in Gram positive and Gram negative bacterial populations.
• the antimicrobial compositions of the present invention may be applied as a wound healing agent, where the composition assists in a faster and qualitatively improved healing of wounds by decreasing the number of microorganisms in the vicinity of the wound.
• the antimicrobial compositions of the present invention may be non-irritating when topically applied to animal or human skin.
• a composition may be determined to be non-irritating based on its Lysis/Denaturation (L/D) ratio as determined by Blood Cell Irritation testing.
• the Blood Cell Irritation tests measures the L/D ratio of a particular composition and is used to determine if a particular composition is mild enough for topical application to the skin or human or animal. Measuring the L/D ratio requires measuring the half haemolysis value (H50) and the denaturation index (DI).
• H50 value relates to the tendency of the red blood cells to rupture when in contact with the test product.
• DI value relates to the denaturation of protein caused by the test product.
• Haemolysis Values H50
• Product Denaturation Index Values DI
• Lysis/Denaturation Ratios L/D
• H50 Haemolysis Values
• DI Product Denaturation Index Values
• L/D Lysis/Denaturation Ratios
• red blood cells To separate the red blood cells, 50 mL of sodium citrate buffer (17.03 g trisodium citrate+8.45 g citric acid diluted to 1 L with bacteria-free DI water) is added to every 450 mL of fresh calf blood and mixed. The blood is then centrifuged to isolate the red blood cells (RBC), which are then washed with phosphate buffered saline solution (PBS) (3.15 g of Na 2 HPO 4 + 0.762 g of KH2PO4 + 7.21 g of NaCI + 1.8 g of glucose diluted to 1 L with bacteria-free DI water), and centrifuged several times to remove white cells and plasma, according to a known method. The red blood cells (“RBC stock”) are then placed into containers for use in testing the compositions of interest.
• PBS phosphate buffered saline solution
• a Standard Surfactant Solution is prepared that includes 1000 ppm sodium lauryl sulfate in PBS. Also, this Standard Surfactant Solution is diluted to 0 ppm, 20 ppm, 30 ppm, and 40 ppm.
• a Test Product Solution is also prepared, which includes 1000 ppm test product in PBS. In addition, this Test Product is diluted to 0 ppm, 25 ppm, 50 ppm, and 100 ppm.
• the H50 value of the Standard Surfactant Solution is first measured. 0.25 mL of adjusted RBC stock suspension is mixed with 9.75 mL of the 40 ppm Standard Surfactant Solution. The mixture is then shaken for 10 minutes and centrifuged for 3 minutes at 5000 rpm to precipitate any intact RBC. The absorbance at 560 nm is measured using the 0 ppm test Standard Surfactant Solution as a blank. This procedure is then repeated for the 20 ppm and 30 ppm Standard Surfactant Solutions. A graph of concentration in ppm vs. absorbance at 560 nm is plotted for the Standard Surfactant Solution.
• the H50 concentration is the concentration where the absorbance is equal to half the absorbance of the 100% haemolysis value (H100), which is determined by mixing 0.25 mL of adjusted RBC Stock with 9.75 mL of DI water, then shaking the mixture for 10 minutes, and then measuring the absorbance at 560 nm.
• the half-maximal haemolytic concentration of sodium lauryl sulfate is 22 + 4 ppm. Obtaining a value in this range confirms that the proper procedure is being followed.
• the H50 value of the Test Product is then measured. 0.25 mL of adjusted RBC Stock suspension is mixed with 9.75 mL of one of the Test Product solutions. The mixture is then shaken for 10 minutes and centrifuged for 3 minutes at 5000 rpm to precipitate any intact RBC. The absorbance at 560 nm is measured using the 0 ppm Test Product sample as a blank. These steps are repeated for each concentration of Test Product solutions. A graph of concentration in ppm vs. absorbance at 560 nm for the Test Product is then plotted. The H50 concentration is the concentration where the absorbance is equal to half the absorbance of the H100. If necessary, additional concentrations of the test product can be prepared so the H50 can be measured accurately.
• the Standard Surfactant Denaturation Index R2 value is measured. 0.25 mL of adjusted RBC Stock suspension is mixed with 9.75 mL of the OOppm Standard Surfactant Solution. The mixture is then shaken for 10 minutes and centrifuged for 3 minutes at 5000 rpm to precipitate any intact RBC. All of the RBC should dissolve. The absorbance at 575 nm and 540 nm is measured using the 0 ppm Standard Surfactant Solution as a blank. The ratio of ABS575/ABS540 is equal to R2. R2 is approximately equal to 0.8. Obtaining a value in this range confirms that the proper procedure is being followed.
• the DI value of the Test Product is determined by first mixing 0.25 mL of adjusted RBC Stock suspension with 9.75 mL of the 1000 ppm Test Product solution. The mixture is then shaken for 10 minutes and centrifuged for 3 minutes at 5000 rpm to precipitate any intact RBC. All of the RBC should dissolve. If the RBC are not completely dissolved, repeat with a higher concentration of Test Product. The absorbance at 575 nm and 540nm is measured using the 0 ppm Test Product solution as a blank. The ratio of ABS575/ABS540 is equal to Ri. The Ri and R2 values are then used to calculate the DI from formula 1 below.
• the H50 score which measures haemolysis alone, usually shows a similar irritation correlation to the L/D ratio. The higher the ppm value for H50 the less irritating the product.
• a crude scale is H50>500 ppm (non-irritant); 120-500 (slight irritant), 30-120 (moderate irritant), 10-30 (irritant), 0-10 (strong irritant).
• the antimicrobial compositions of the present invention may exhibit an H50 value of at least 300, 400, 500, 600, 700, or 800 ppm.
• the DI score which measures denaturation of protein also shows a correlation to the L/D ratio.
• a crude scale is DI 0-5% (non-irritant); 5-10% (slight irritant), 10-75% (moderate irritant), 75-100% (irritant), and >100% (strong irritant).
• the antimicrobial compositions of the present invention may exhibit a DI score of less than about 10, 7, 5, 3, 1 , 0.5, or 0.3%.
• the L/D ratio is the primary value typically used to determine irritation.
• An L/D value greater than 100 is an indication that the composition is a non-irritant; levels between 10 and 100 are considered slight irritants; levels between 1 and 10 are considered moderate irritants; levels between 0.1 to 1 are considered irritants; and levels lower than 0.1 are considered strong irritants.
• the antimicrobial compositions of the present invention exhibit an L/D ratio of at least 100, 150, 200, 250, or 300.
• skin conditioning and moisturizing agents are at best unnecessary, and at least may be minimized in a particular product.
• Methods of preparing the antimicrobial compositions of the present invention may involve dissolving a desired concentration of antimicrobial agents and, optionally, any desired additives in a selected solvent, namely water. The solution is then mixed, for example in a mixer, to form a final antimicrobial composition.
• the components of the disclosed antimicrobial compositions fall within the ranges set forth in Tables I and II below.
• Table I identifies exemplary ready-to-use antimicrobial compositions in accordance with certain embodiments of the present invention.
• Table II describes preferred ready-to-use antimicrobial compositions in accordance with certain embodiments of the present invention.
• compositions that are efficacious as bactericides and yeasticides.
• the compositions can be formulated to be physically stable at cold temperatures.
• each component concentration is 100% active unless that component is expressly identified as having a certain percentage of active versus inert ingredients. For example, if a component is listed as “Glycolic acid, 70%” and is shown to be present at 4.28 wt. %, this means that glycolic acid is present in that composition at 3 wt % (0.7 * 4.28 wt. %).
• Example 1 Microbiological Activity of Formulations Having Varying Concentrations of Salicylic Acid, Glycolic Acid, and Anionic Surfactants
• test methods are in place for comparatively testing the efficacy of antimicrobial agents.
• test methods EN 1656 bacteriaicidal activity
• EN 1657 yeasticidal activity
• the microorganisms E. coli (ATCC 11229), S. aureus (ATCC 6538), and Streptococcus uberis) are prepared from glycerol stocks that are spread onto tryptic soy agar plates and allowed in incubate for 24 hours. This is the stock culture. A subculture is then prepared from the stock culture by streaking tryptic soy agar plates and allowing incubation for 24 hours. Second and third subcultures are prepared from the first subculture in the same way. These subcultures are the working cultures. Loopfuls of the working cultures are then transferred to diluent to create a standardized cell suspension, this suspension is used in the testing against the compositions. The bacteria were diluted to form a suspension having an initial concentration of about 10 8 cfu/mL.
• a mixture of 10 g/L bovine albumin and 10 g/L yeast extract was used as an interfering substance under high soil conditions, and 3 g/L bovine albumin was used as interfering substance under low soil conditions, in testing under EN 1656 protocol.
• Yeast extract comprises the cell contents of yeast without the cell walls and are often used as food additives or flavorings, or as nutrients for bacterial culture media.
• yeast are exposed to an interfering substance before being exposed to the composition.
• the interfering substance was a mixture of 10 g/L bovine albumin and 10 g/L yeast extract (high soil), and 3 g/L bovine albumin (low soil), respectively.
• the microorganism used to evaluate disinfection was Candida albicans ATCC 10231 (C. albicans).
• the microorganisms are prepared from glycerol stocks that are spread onto malt extract plates and allowed in incubate for 42-48 hours. This is the stock culture. A subculture is then prepared from the stock culture by streaking malt extract agar plates and allowing incubation for 42-72 hours. Second and third subcultures are prepared from the first subculture in the same way. These subcultures are the working cultures. Loopfuls of the working cultures are then transferred to diluent to create a standardized cell suspension, this suspension is used in the testing against the compositions. The yeasts were diluted to form a suspension having an initial concentration of about 10 7 cfu/mL.
• Standard general disinfection temperature is 10°C; however, 30°C is a more realistic teat disinfection temperature. All reagents used in the testing of the compositions are equilibrated to temperature before the testing begins. The standard contact time for general disinfection is 30 minutes; however, the practical contact time for pre-milking teat disinfection is 1 minute.
• Table III Table IV [0080] The results from Table III and IV demonstrate several noteworthy trends. Yeasticidal efficacy appears to be influenced by several factors, namely the presence of salicylic acid, the quantity of glycolic acid, and the quantity of the anionic surfactant sodium lauryl sulfate (SLS). As can be seen in Formulations 33 and 34, when no salicylic acid is present, the formulations do not exhibit acceptable yeasticidal efficacy. And, although in Formulation 18, yeasticidal efficacy can be achieved in the absence of salicylic acid, this formulation requires at least 10% glycolic acid, which would render it quite irritating to animal skin, and the formulation does not exhibit passing low temperature stability.
• SLS sodium lauryl sulfate
• At least a certain minimal level of glycolic acid is required to support the yeasticidal efficacy of salicylic acidcontaining formulations under high soil conditions.
• formulation 41 has a 5.4 log reduction of C. albicans under high soil conditions.
• formulations 14, 15, 27, and 35 at least a certain minimal level of SLS is required to support the yeasticidal efficacy of formulations comprising both salicylic and glycolic acids.
• the term “and/or,” when used in a list of two or more items, means that any one of the listed items can be employed by itself or any combination of two or more of the listed items can be employed. For example, if a composition is described as containing components A, B, and/or C, the composition can contain A alone; B alone; C alone; A and B in combination; A and C in combination, B and C in combination; or A, B, and C in combination.
• the terms “comprising,” “comprises,” and “comprise” are open-ended transition terms used to transition from a subject recited before the term to one or more elements recited after the term, where the element or elements listed after the transition term are not necessarily the only elements that make up the subject.

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