AND METHODS OF USING SAME

BACKGROUND OF THE INVENTION

The present invention relates to compositions and methods of providing rapid and persistent control of a broad-spectrum of microbes on mammalian surfaces by topical application of compositions.

Lameness of diary cows and sheep is one of the major problems facing the dairy and meat industry, respectively, today. The cost of lameness is measured by lost milk production, culled cows, underweight meat animals, additional labor, veterinary bills, and medicines for treatment. In the United States, the annual overall cost of lameness is estimated to exceed 570 million dollars. It is especially a problem in large herds, which are the fastest growing segment of the market. The prevalence of lameness in large herds is 50% or more.

Lameness is, in many cases, caused by anaerobic organisms such as

Arcanobacterium pyogenes (previously called Corynebacterium pyogenes), in particular where the infection goes into the deep structure of the hoof. In sheep the infection may be accompanied by swelling and a white to black pus discharge.

There are multiple causes for lameness ranging from lack of general stable hygiene, specific hoof hygiene, hoof care, malnutrition, general genetic disposition, specific genetic defects to bacterial and viral infections. For example, fibroma (corns) is a genetic condition found in cattle which causes a hard, fibrous lump to form between the claws of the foot. The corn makes the hoof more susceptible to subsequent bacterial and viral infections. These infections occur at various locations in and around the hooves of the cattle. In addition to the general lesions caused by infection, a disease of unknown etiology has been spreading throughout the western United States. This disease is digital dermatitis. Digital dermatitis is characterized by painful lesions, which often are surrounded by a ridge of hyperkeratotic (thickened) skin with finger like projections. Due to its appearance, the disease is commonly referred to as hairy wart or strawberry disease; it is also known as Mortellaro disease.

Studies have shown that a third of all lameness in cows is caused by digital dermatitis. Digital dermatitis is present worldwide and is estimated to be present in 41% of herds smaller than 100 cows, and from 64% to 82% in larger herds.

Other contagious and debilitating diseases of the bovine foot and hoof include such conditions as bovine hoof rot and interdigital dermatitis. In addition to causing lameness in diary cows, these contagious diseases also cause a significant decrease in milk production and sometimes death. Dairy farmers report as much as 50% less milk being produced per cow. (Linda Leake, Farm Journal, Inc., (1998).) In sheep, in addition to causing lameness and reduced production, foot rot is highly contagious sometimes resulting in a whole flock becoming infected. (Government of Newfoundland and Labarador 2004)

For years, directing animals through hoof baths containing hoof care solutions has been practiced as an aid to general hoof health and hygiene for the prevention of, and a cure for, diseases of the animals' hooves. Materials used for these solutions include copper sulfate, zinc sulfate, formaldehyde, quaternary ammonium compounds, peroxides, organic acids, and their combinations, and certain antibiotics. Additionally, several over the counter commercially compounded liquid products have been and are being used. Major manufacturers of this latter category are Delaval (DoubleAction), Westfalia-Surge (Pedicure Rx), and SSI Corporation (Healthy Foot). Copper sulfate, zinc sulfate and other heavy metal based antimicrobials are usually applied in 5% to 10% solutions to be effective. Recently, the negative environmental impact of the use of heavy metal compounds has been recognized. Efforts have been made to use mixed salts in combination with specific additives in order to reduce the overall use of heavy metal (to concentrations as low as low as 0.5%). However, despite regulatory restrictions, heavy metals are still in use since no effective alternative products are presently on the market.

Hoof baths are generally located in the return alley of dairy milking barns or parlors. After being milked, the animals typically walk through the hoof bath on the way back to where they are housed. The feet and hooves will typically contain accumulated dirt and manure. This is especially true in modern dairy facilities with housing contained in limited areas such as free stall or tie stall barns or dry lots instead of open pasture.

In addition, on passing through the hoof bath, the cows may defecate into the hoof bath. The added organic material or load to the hoof bath compromises the antimicrobial products' ability to work in the disinfection and cleansing of the cow hooves where the causative microorganisms are located. For economic reasons, the use of antibacterial chemical and biological products in doses high enough to compensate for the organic material present in the hoof bath and to penetrate through organic material and whatever tissue may conceal or otherwise harbor the bacterial pathogens, is usually cost prohibitive. Other chemical products that are less expensive to use at higher doses have the disadvantage in that they may be toxic to the animals, to the people working in the dairy facilities, and, particularly, to the environment. Heavy metal moieties of the compounds do not break down and accumulate in the environment. Accordingly, there is a need for a more effective and environmentally friendly manner by which to treat and prevent hoof diseases in bovine livestock. In particular, a need exists for an effective, convenient method to control a broad spectrum of microbes that is fast-acting, has long-lasting efficacy, and is mild to livestock. SUMMARY OF THE INVENTION

In one aspect, the present invention provides a dry composition comprising: active ingredients comprising i) a cosmetic dye selected from a violet, blue or green dye, or combinations thereof, and ii) at least one enhancing ingredient, wherein the relative weight percentage of the cosmetic dye to the enhancing ingredient is about 90 : 1 to about 99 : 1, wherein the cosmetic dye interacts with keratin ous material in an aqueous environment. The dye provides the composition with a color upon exposure to an aqueous environment, wherein the loss of the color signifies the loss of effectiveness of the composition. Preferably, the aqueous environment is a hoof bath.

In one embodiment, the present invention provides a hoof bath sanitation unit comprising: a container which is dissoluble in an aqueous environment, wherein the container contains a dry composition comprising: active ingredients comprising i) a cosmetic dye selected from a violet, blue or green dye, or combinations thereof, and ii) at least one enhancing ingredient, wherein the relative weight percentage of the cosmetic dye to the enhancing ingredient is about 90 : 1 to about 99 : 1, wherein the cosmetic dye interacts with keratinous material in the presence of an aqueous environment. The dye provides a hoof bath with a color, wherein the loss of the color signifies the loss of antimicrobial effectiveness of the hoof bath.

In another aspect, the present invention provides a method of inhibiting disease in a bovine mammal comprising: placing a dry composition into an aqueous bath, wherein the dry composition comprises: active ingredients comprising i) a cosmetic dye selected from a violet, blue or green dye, or combinations thereof, and ii) at least one enhancing ingredient, wherein the relative weight percentage of the cosmetic dye to the enhancing ingredient is about 90 : 1 to about 99 : 1, wherein the relative weight percentage of the active ingredients to water is about 1 : 5 to about 1 : 1000; and exposing the mammal to the aqueous bath, wherein the cosmetic dye interacts with keratinous material of the mammal, and wherein the dye provides the bath with a color, wherein the loss of the color signifies the loss of effectiveness of the aqueous composition.

In a further aspect, the present invention provides a method of maintaining hygiene of a hoof bath comprising: placing a dissoluble pouch containing a dry composition into a hoof bath, wherein the dry composition comprises: active ingredients comprising i) a cosmetic dye selected from a violet, blue or green dye, or combinations thereof, and ii) at least one enhancing ingredient, wherein the relative weight percentage of the cosmetic dye to the enhancing ingredient is about 90 : 1 to about 99 : 1, wherein the relative weight percentage of the active ingredients to water is about 1 : 5 to about 1 : 1000; and wherein the cosmetic dye interacts with keratinous material of a mammal, and wherein the dye provides the bath with a color, wherein loss of the color signifies the loss of hygiene of the hoof bath. In an additional embodiment, the present invention provides a method of indicating whether a hoof bath is antimicrobial comprising: placing a dissoluble pouch containing a dry composition into a hoof bath, wherein the dry composition comprises: active ingredients comprising i) a cosmetic dye selected from a violet, blue or green dye, or combinations thereof, and ii) at least one enhancing ingredient, wherein the relative weight percentage of the cosmetic dye to the enhancing ingredient is about 90 : 1 to about 99 : 1, wherein the relative weight percentage of the active ingredients to water is about 1 : 5 to about 1 : 1000; and wherein the cosmetic dye interacts with keratinous material of a mammal, and wherein the dye provides the bath with a color, wherein loss of the color signifies the loss of antimicrobial effectiveness of the bath.

In any of the methods of the present invention, the dry composition can be enclosed in a dissoluble pouch containing the dry composition when placed into an aqueous environment, such as, for example, a hoof bath. Preferred examples of the cosmetic dye include Gentian Violet, Brilliant Green,

Toluidine Blue, or combinations thereof. Preferred examples of the enhancing ingredient is selected from the group consisting of halogenated isothiazolin-3-ones; formaldehyde depot substances;

chloracetamide; hexetidine; O-phenylphenol; 2,4-dichlorobenzylalcohol; trichlorcarban; glyoxal; chlorocresol, sodium hydroxymethylglycinate; sodium 2-biphenylate, chlorhexidine digluconate; chlorhexidine diacetate; hexamidine; phenoxyethanol;

biphenyl-2-ol, formic acic, benzoic acid, salicylic acid, lactic acid, tannic acid, symclosene, sodium dichloroisocyanurate dehydrate, sorbic acid, methyl paraben;

bronopol; triclosan; chlorhexidine; chlorhexidine digluconate, 5-isopropyl-2- methylphenol; 4-chloroxylol; DMDM-hydantoine; chlorophene, chloramin-T, benzylalcohol; cyanamide, phenoxyisopropanol; dimethyloxazolidine;

benzylhemiformal; silver chloride, chlorobutanol; imazalil, sodium p-chloro-m-cresolate, diamine, troclosene sodium, phenol; herbal extracts, thymol, menthol, rosemary oil, carvacrol, magnolia bark extract and synthetics. BRIEF DESCRIPTION OF THE DRAWINGS

Figure 1 shows the influence of hoof bath contamination on the composition of the present invention (at 2% and 4% concentrations) versus copper sulfate (at 2.5% and 5% concentrations) after 4 hrs, 24 hrs, 48 hrs and 96 hrs.

Figure 2 shows the influence of hoof bath contamination on the composition of the present invention (at 2% and 4% concentrations) versus formaldehyde (at 2% concentration) after 4 hrs, 24 hrs and 48 hrs. Figure 3 shows the influence of hoof bath contamination on the composition of the present invention (at 2% and 4% concentrations) versus glutaraldehyde (at 2% concentration) after 4 hrs, 24 hrs and 48 hrs.

Figure 4 shows the influence of hoof bath contamination on the composition of the present invention (at 2% and 4% concentrations) versus benzalkonium chloride (at 1% concentration) after 4 hrs, 24 hrs, 48 hrs and 72 hrs. DETAILED DESCRIPTION OF THE INVENTION

The present invention provides dry compositions, and methods to topically treat mammalian microbial disease and infection, and lesions and wounds resulting therefrom, with such compositions. The dry compositions are substantially (e.g., entirely) free of moisture, e.g., free of water.

The compositions and methods of the present invention enable killing a broad spectrum of bacteria, while simultaneously inactivating or destroying viruses and fungi. The compositions are fast- acting and provide long-lasting efficacy.

Throughout this specification, quantities are defined by ranges, and by lower and upper boundaries of ranges. Each lower boundary can be combined with each upper boundary to define a range. The lower and upper boundaries should each be taken as a separate element.

In one embodiment, the active ingredients of the dry compositions of the present invention comprise i.) a violet, green or blue cosmetic dye, or combinations thereof, and ii.) at least one cosmetic preservative and/or antimicrobial (hereinafter "enhancing ingredient").

The cosmetic dye comprises a cationic nitrogen, wherein the cationic nitrogen is connected to a double bond of an aromatic carbon. The cationic nitrogen has bonds to only three carbon atoms, including one double bond to an aromatic carbon. This double bond to the cationic nitrogen can oscillate from one to all the other possible cationic nitrogen atoms in the molecule giving the molecule the color.

Examples of suitable violet, green and blue cosmetic dye include Gentian Violet, Brilliant Green and Toluidine Blue. These dyes can be 4-[(4-dimethylaminophenyl)- phenyl-methyl]-N,N-dimethyl-aniline; and (7-amino-8-methyl- phenothiazin-3-ylidene)- dimethyl-ammonium. Further examples include Brilliant Blue FCF, Ethyl Green, Green S, and Victoria Blue BO.

It has surprisingly been discovered that at a certain relative amount of the cosmetic dye to the enhancing ingredient, the antimicrobial efficacy of the component parts of the compositions of the present invention are synergistically enhanced.

The preferred relative weight percentage of the cosmetic dye to the enhancing ingredient has a range of about 90 : 1 to about 99 : 1. Examples of other preferred boundaries of this range include 95 : 1 and 97 : 1. Examples of other preferred ranges are about 95 : 2 to about 98.9 : 1.

Examples of other ranges of the cosmetic dye to the enhancing ingredient are of about 50 : 1 to about 90 : 1. Examples of other lower boundaries of this range include 60 : 1; 70 : 1 and 80 : 1. Examples of other upper boundaries of this range include 85 : 1; 75 : 1 and 65 : 1.

As specific examples, the relative weight percentage of the cosmetic dye to the enhancing ingredient is about 98.894 : 0.1057 or about 98.8 : 0.2. For example, the enhancing ingredient can be present in about 0.2 to about 5 wt.% of the composition.

In the end use compositions of the present invention, the relative weight percentage of the active ingredients to water is about 1 : 5 to about 1 : 1000, or about 1 : 25 to about 1 : 1000. Examples of other preferred lower boundaries of this range include about 1 : 10; about 1 : 100; 1 : 200, 1 : 400 and 1 : 500. Examples of other preferred upper boundaries of this range include 1 : 500; 1 : 750; and 1 : 900.

For example, in a preferred embodiment, the end use composition contains approximately a maximum of 3 wt.% active ingredients and 97 wt.% water. For instance, the active ingredients can be 0.31 wt.% of the end use composition. Accordingly, in such example, the corresponding amount of water is about 99.69wt. so that the actives to water ratio is about 0.31 : 99.69 or 1 : 322.

In a preferred example, about one pound of a dry composition of the present invention is added to about 50 gallons of water to form an end use composition.

In some embodiments, the compositions of the present invention can further comprise a gelling and/or thickening agent wherein the ratio of the active ingredients to the agent is about 2: 1 to 1 to 40. Examples of such agents include gums, xanthan gum, cellulose, methylcellulose, carboxymethylcellulose, chitosan, alginates, polysaccharides, their derivatives and combinations thereof.

In a preferred embodiment, the compositions do not include quaternary ammonium compounds. (In quaternary ammonium compounds, the cationic nitrogen has four separate bonds to four carbon atoms.) Also, in a preferred embodiment, the compositions also do not include and/or do not include an anticoagulant and/or do not include peroxides and/or do not include heavy metal based antimicrobials. Some examples of anticoagulants include heparin, hirudin, EGTA, urokinase, streptokinase, and hydrogen peroxide. Some examples of heavy metal based antimicrobials include copper sulfate and zinc sulfate. In a preferred embodiment, the compositions do not include cosmetic preservatives based on an organic acid except for tannic acid. The compositions also preferably do not include harsh chemicals, such as, for example, formaldehyde and/or glutaraldehyde, and/or do not contain antibiotics. The synergistic combination of the i) cosmetic dye and ii) the enhancing ingredient(s) decrease the minimum inhibitory concentration (MIC) of each individual component. Also, the active ingredients of the present invention are effective at a much lower concentration than the active ingredients of other antimicrobial compositions which use dyes or cosmetic preservative compounds; and are effective at a much lower concentration than heavy metal based antimicrobials. Additionally, the combination of the cosmetic dye and the enhancing ingredient(s) increase the spectrum of microbes that each component could individually target. The compositions of the present invention enable killing a broad spectrum of bacteria, including Gram positive and Gram negative bacteria such as S. aureus, S. choleraesuis, E. coli, K. pneumoniae, and anaerobic bacteria, such as, for example, Arcanobacterium pyogenes while simultaneously inactivating or destroying viruses and fungi. The cosmetic dyes suitable for the compositions are dyes which interact (e.g., bind) with keratinous material when acting synergistically with the enhancing ingredients of the present invention.

Further, once the compositions of the present invention contain water, the compositions degrade. Thus, the compositions are environmentally friendly and do not interfere with the operation of the digester.

The dry compositions of the present invention are allows ease of transport.

Typically, dry composition comprises about 0.2 to about 5 wt.% of a dry enhancing ingredient (e.g., crystalline form) with the balance being substantially the cosmetic dye dry form. The end use compositions of the present invention are fast-acting and long- lasting. In particular, the end use compositions quickly penetrate porous keratinous material (e.g., keratinous material of skin tissue, hooves, finger/toe nails, and hair). Once the site of interest (i.e., the target site) is in contact with the composition for few seconds, the cosmetic dye interacts with the keratinous material of a mammal in such a way that it is resistant to leaching.

Because the composition is resistant to leaching, the duration of the antimicrobial activity is increased. For example, at least about 90%, about 80%, about 70%, about 60%, about 50%, or about 40% of the composition remains at the target site despite exposure to percolating water. This property of the composition is very beneficial when applied to bovine livestock since such animals are typically exposed to environmental water, for example, while grazing.

Additionally, the cosmetic dye substantially stains the target site. Such staining is a useful property of the compositions. For example, the dye indicates the presence of the active ingredients, and their penetration depth; that is, the protected zone is clearly elucidated. Using this indicator feature of the composition, it has been demonstrated that even after extensive exposure to percolating water, the depth of penetration of the composition and its intensity of staining are not diminished.

In one embodiment, the active ingredients of the present invention consists essentially of (or consists of) a cosmetic dye and at least one enhancing ingredient. That is, other ingredients that may materially affect the basic and novel characteristics of the active ingredients of the invention are specifically excluded from the composition. The active ingredients are the cosmetic dye(s) and the enhancing ingredient(s) of the compositions of the invention. Preferably, such composition also includes a stabilizer.

A typical pH range of the end use compositions of the present invention is from about 2.5 to 7. The end user typically may make about 2% to 5% aqueous solution for a hoof bath. Such a solution typically has a pH of slightly below about 3.5. In actual use, when cows walk through a 2% hoof bath and drop manure, the pH typically gradually rises to above about 4. A pH of below about 7 does not typically decrease the efficacy of the compositions. Methods of Use

The present invention includes a method of treating mammals by topically applying the compositions to desired target sites. In this specification "treating" refers to inhibiting disease; preventing disease; aiding in the prevention of disease; assisting in healing lesions; maintaining or increasing the hygiene level, or combinations thereof. Typical target sites include sites on the body that are susceptible to microbial infection and are prone to lesions and wounds. The diseases which can be treated by the methods of the present invention include any microbial infections; lesions or wounds that result from such infections; and lesions or wounds that are vulnerable to such infections. The invention is particularly well suited for treating bovine mammals, in particular, bovine livestock. Examples of bovine mammals include cows, cattle, and ox, The compositions are also suitable for ovine, caprine, hircine and corvine animals, such as, for example, sheep, goat, deer, yak, buffalo, antelope, bison, deer and elk. Examples of diseases which can be treated include diseases related to hooves, including, for example, hoof rot, hoof wart, digital dermatitis, interdigital dermatitis, foot rot, strawberry disease (Mortellaro disease) and/or bacterial, viral and fungal infections.

One common application mode for hoof diseases is a hoof bath or a foot bath. For example, the composition can be used in such a way that animals walk through an aqueous composition of the dry composition, thereby preventing the spread of microorganisms, and also providing an opportunity to treat any infections on the hooves of the animals. Alternatively, the composition can be formulated and applied such that farm workers walk through the aqueous composition, thereby preventing microorganisms on their boots from spreading. In one embodiment, the present invention provides a hoof bath sanitation unit comprising: a container which is dissoluble in an aqueous environment, wherein the container contains a dry composition of the present invention. For example, the dry composition of the present invention is placed into a substantially dissolvable container, e.g., a pouch, a bag. Examples of such containers include polyvinyl alcohol bags. Such bags are available in a variety of grades, e.g., cold, warm and hot water soluble. The container holding the dry composition is placed into a hoof bath. The container and the dry composition dissolve quickly into the hoof bath.

For example, a pouch containing about one pound of a dry composition of the present invention can be added to 50 gallons of water in a hoof bath. One such pouch can be used for about 250 cows. In some embodiments, the present invention provides a hoof bath which comprises an indicator by which to determine whether the hoof bath is effective. The cosmetic dye provides the bath with a color. For example, brilliant green provides the bath with a uniform blue color. Once the bath loses its color (e.g., its blue color), the bath is no longer effective. Also, the hooves are stained with the dye. Once the hooves lose the dye color, the hooves are no longer protected. Thus, the methods of the present invention provide an easily discernable visual cue signaling whether the compositions are still effective.

In some embodiments, the present invention provides a method for preventing microbes in a hoof bath from spreading, and a method for keeping a hoof bath hygienic. The dry composition is placed into a hoof bath, as described above.

In some embodiments, the present invention provides a method for determining whether a hoof bath is effective in killing microbes. The dry composition is placed into a hoof bath, as described above. Once it is observed that the hoof bath loses its original color, the hoof bath is no longer effective.

The compositions of the present invention have a biodegradation time of about two weeks. Thus, hoof/foot baths using these compositions in conjunction with biogas generators is valuable, since they do not impair the biogas generation. Copper sulfate is not suitable for such use because of its long term influence on the digester system stopping the biogas production, in addition to their negative environmental impact.

In one embodiment, an application mode for treating mastitis is a teat dip. The composition is placed in a small container with a shape adapted to the teat. The teat is then dipped into the container filled with the composition. Another application mode is spraying the udder including the teats. "Enhancing Ingredients"

Preferably, the enhancing ingredients include cosmetic preservative(s) and/or antimicrobials, such as, for example, halogenated isothiazolin-3-ones; formaldehyde depot substances; chloracetamide; hexetidine; O-phenylphenol; 2,4-dichlorobenzyl- alcohol; trichlorcarban; glyoxal; sodium hydroxymethyl-glycinate; chlorhexidine digluconate; chlorhexidine diacetate; hexamidine; phenoxyethanol; methyl paraben; bronopol; triclosan; chlorhexidine; 5-isopropyl-2-methylphenol; 4-chloroxylol; DMDM- hydantoine; benzylalcohol; phenoxyisopropanol; dimethyloxazolidine;

benzylhemiformal; chlorobutanol; phenol; and herbal extracts and/or synthetics, for example, thymol, menthol, rosemary oil, carvacrol, and the like.

Other example of preferred enhancing ingredients (i.e., specific cosmetic preservative(s) and/or antimicrobials) is/are chlorocresol; sodium 2-biphenylate;

biphenyl-2-ol; formic acid; benzoic acid; salicylic acid; lactic acid; tannic acid;

symclosene; sodium dichloroisocyanurate dehydrate; sorbic acid; chlorhexidine digluconate; chlorophene; chloramin-T; cyanamide; silver chloride; imazalil; sodium p- chloro-m-cresolate; diamine; troclosene sodium; and magnolia bark extract. Further examples include polycarboxylic acid (e.g., malic acid, tartaric acid, citric acid, glutaric acid); saturated organic aliphatic mono carbonic acids; alpha/beta mono carbonic acids (e.g., hydroxyl in alpha/beta position, keto in the alpha/beta position); aromatic monocarbonic acids, including those with substituents in the rings; and mandelic acid and its derivatives. These organic acids are provided in crystalline form in the dry compositions.

Examples of Organic Acids Used as Enhancing Ingredient(s)

The testing of organic acids used as an enhancing ingredient in the present invention against microorganisms involved in hoof rot/wart was done according to Hydromer QC Testing protocol MCR 3.0 Membrane Filter Technique. The results summarized in the Table below.

Low Efficacy - up to 50% of Growth inhibition.

Moderate Efficacy - from 50 to 70 % of Growth Inhibition.

Strong Efficacy - up to 90 % of Growth Inhibition

Auxiliary Substances

In addition to the active components, the above mentioned compositions can include other, non-toxic auxiliary agents, as long as such agents do not detract from the benefits provided by the present therapeutic compositions. These agents can, for example, facilitate the delivery and efficiency of the therapeutic agent and/or stabilize the composition (e.g., cosmetic stabilizers) with respect to its shelf life or its actual outdoor applications. The preferred range of these agents in the composition is about 0.05% to 12%. For example, these compositions can contain water-soluble skin conditioning or moisturizing agents that do not interfere with the synergistic antimicrobial properties of the compositions. Examples of these ingredients are glycerin; glycols; polyols, such as polyethylene glycol; lanolin; aloe vera, grapefruit seed extract, and vitamins, such as E, C and A. These agents serve to assist in soothing and retaining moisture on the skin.

Examples of stabilizing agents (i.e., stabilizers) include cosmetic stabilizers; radical scavengers; antioxidants; and UV absorbers e.g., cinnamate derivatives, benzophenone derivatives, vitamins and the like.

Agents such as colorants, fragrances and insect repellants (e.g., citronella) may also be included in the composition. Other examples of agents include preservatives, excipients, pH buffering agents, alcohols, chelating agents (e.g., EDTA), film-forming or barrier forming hydrophilic binder combinations ( e.g. polyurethanes and polyvinyl pyrrolidone) or other therapeutics that do not contaminate meat or dairy products produced by the animal, and mixtures thereof.

Carrier agents can also be included in the end use aqueous compositions of the present invention. However, typically, the composition is used without being placed on, or in, a substrate. For example, the composition is not placed onto a polyurethane polymer and/or not used in moldable/pliable compositions. An example of a

moldable/pliable composition is a composition which comprises flour.

EXAMPLES

Digital dermatitis, mastitis and other related microbial infections in animals can effectively be treated by a topical application of the compositions of the present invention.

Example 1

Dry Composition contains the following ingredients:

The composition is placed into a one pound dissolvable pouch, and placed into a 50 gallon hoof bath.

Example 2

Comparative Example

This example shows the influence of hoof bath contamination by dirt and manure on the effectiveness of a composition of the present invention (at 2% and 4%

concentrations) as compared with copper sulfate (at 2.5% and 5% concentrations). As can be seen in Figure 1, the present composition remains effective up to at least 48 hours after contamination; whereas, the control lose effectiveness even after 4 hours. .

Example 3

Comparative Example

This example shows the influence of hoof bath contamination by dirt and manure on the effectiveness of a composition of the present invention (at 2% and 4%

concentrations) as compared with formaldehyde (at 2% concentration). As can be seen in Figure 2, the present composition remains effective up to at least 48 hours after contamination; whereas, the control lose effectiveness even after 24 hours. Example 4

Comparative Example

This example shows the influence of hoof bath contamination by dirt and manure on the effectiveness of a composition of the present invention (at 2% and 4%

concentrations) as compared with glutaraldehyde (at 2% concentration). As can be seen in Figure 3, the present composition remains effective up to at least 48 hours after contamination; whereas, the control lose effectiveness even after 24 hours. Example 5

Comparative Example

This example shows the influence of hoof bath contamination by dirt and manure on the effectiveness of a composition of the present invention (at 2% and 4%

concentrations) as compared with benzalkonium chloride (at 1% concentration). As can be seen in Figure 4, the present composition remains effective up to at least 72 hours after contamination; whereas, the control lose effectiveness even after 24 hours.