MXPA00002483A - Germicidal compositions for the treatment of animal infectious diseases of the hoof, comprising a copper salt, a quaternary ammonium compound and a peroxide - Google Patents

Abstract

An aqueous germicidal composition for the treatment or prevention of infectious diseases of the hoof in animals, comprising a copper salt, a quaternary ammonium compound, and a peroxide is disclosed. A method for treating or preventing infectious diseases of the hoof in animals, comprising topically administering an effective amount of an aqueous germicidal composition comprising a copper salt, a quaternary ammonium compound, and a peroxide is also disclosed.

Description

GERMICIDAL COMPOSITIONS FOR THE TREATMENT OF INFECTIOUS DISEASES OF ANIMAL FISH, COMPRISING A COPPER SALT, A COMPOSITE OF QUATERNARY AMMONIUM AND A PEROXIDE DESCRIPTION OF THE INVENTION The present invention relates to the treatment and prevention of infectious diseases of the hooves in animals. . Infectious diseases of the hooves such as hairy hoof warts (digital papillomatous dermatitis, or "PDD") hooves of hoof (interdigital phlegmon), and hock of stable hoof (interdigital dermatitis) are common in farm animals such as sheep, goats, horses, dairy cows and cattle for meat. Hoof warts were first reported in Italy in 1974, and since that time, it has spread throughout the world. Since the late '80s, hoof warts have been a significant source of bovine lameness, and have had a broad economic impact on the dairy industry. For example, a recent study by the United States Department of Agriculture concluded that 47% of dairy herds in the United States are affected by the DDA, with 78% of those who reported their first cases in 1993 or later. See Digi tal Derma ti tis on U. S. Dairy Operations, NAHMS Dairy Study, May 1997.

Clinically, the PDD appears as an outbreak of lameness of varying severity within a specific special herd. This is a superficial skin disease of the animal digit with variable presentation, depending on the stage of the lesion, from pain, wet, lesions arising as strawberries, hairy, wart-like lesions. This can result in severe lameness, and even death if not treated properly. With respect to dairy cows, the warts on the hooves are also associated with losses in milk production, efficient reproduction and body weight. Although the PDD was originally believed to be caused by a virus, it is now believed that the PDD is caused by one or more bacteria. Researchers have isolated two different spices of spirocheta bacteria from numerous PDD lesions, but have been unable to replicate the infectious disease in healthy animals using cultures purified from these organisms. This means that the causative agent and / or additional environmental conditions are necessary to bring the disease. The hoarseness of the hoof or interdigital phlegmon, is an infection of the soft tissue between the toenails. In equine animals, they are also known as hoof arestín. In the present, the term "hoof hooves" will be used to indicate both hoof hooves and hoof hooves. The hoof hoarseness is caused by the anaerobic bacteria, Fusuba cterium necrophorum. The anaerobes Díchelobacter (Bacteroides) nodosus and Prevotella melanínogenicus have also been implicated. The bacterium invades the skin of the paw in wounded or damaged areas of the skin, and initially causes a painful swelling of the skin between the nails. A fissure or crack then develops along the swollen area on part or all of the length of the interdigital space. If left untreated, hoof hooves may enter the joints, bones and / or tendons of the paw, causing it to become coated with the undesirable infection. The hoofed animals may have a slight fever, loss of appetite and accompanied by weight loss, and a slight development to severe lameness. Interdigital dermatitis or hock of stable hoof, is usually a chronic inflammation of the skin in the area between the hooves of the legs (cracked interdigital). This infection is caused by the bacteria Dicheloba cter nodosus. The skin in the interdigital cracked area will appear swollen with a dry exudation that will cause a crust in the form. The condition can occasionally cause lameness or heel cracking / heel erosion but generally results in an alteration in the animal's gait.

Currently, hoof warts, claw hooves and hoof hooves are treated in various ways. The most effective treatment is the use of antibiotics, such as tetracycline, lincomycin, spectinomycin, penicillin, oxytetracycline and ampicillin, which are applied topically to the affected areas through the use of leg baths, sprays or leg wraps. While antibiotics are effective in treating these infectious diseases, there are severe disadvantages with the use of antibiotics. Antibiotics are expensive, and are especially related to dairy cows, that the use of antibiotics can result in the presence of antibiotic residues in the animal or its milk. In addition, the widespread use of antibiotics may result in the development of a strain of bacteria resistant to the antibiotic. Finally, at present, the use of antibiotics for the treatment of hoof hooves, hoof hooves or PDD is "out of level", that is, antibiotics are not specifically approved for these uses. The use of germicides based on chemicals has been proven as a treatment to prevent and / or control hoof hoarseness, hoof warts, and hoof hoarseness. Although some germicides, such as those containing copper sulfate and zinc sulfate, have some efficacy against hoof hooves and hoof hooves are ineffective against hoof hooves. Quaternary ammonium compounds have been used but have never been tested to be effective against PDD. Such • compounds are also ineffective in such solutions, such as those used in leg baths, and many are expensive. Similarly, combinations of hydrogen peroxide and peracetic acid have been used, although they have not been effective against PDD, and suffers from stability and storage problems. This chemical combination is also irritating to the hooves in the concentrations • Recommended treatment. There have been anecdotal reports of success with formaldehyde against PDD, but controlled trials indicate that formaldehyde is more effective than antibiotics.

Additionally, formaldehyde is classified as a carcinogen and toxin, and is illegal in some parts of the United States. In addition, the high use of formaldehyde concentration can result in destruction of the tissues of • the healthy hoof, or can still stop detaching from the hoof In this way, the use of formaldehyde is neither viable nor effective in the treatment * of hoarseness of hoof, hock of stable hoof and PDD. As stated in the foregoing, footbaths comprise a germicide, such as a copper sulfate or Hydrogen peroxide, or even an antibiotic, are commonly used to try to prevent claw hooves, hoof hooves, and / or PDD. Leg baths are typically spray dilutions or compositions that wrap the legs. However, the germicide or antibiotic present in these leg baths can easily be overcome by the harsh environmental conditions to which the bath is subjected. As a result, these baths can become a breeding zone for bacteria, and can thus accelerate the spread of disease from infected hooves, instead of preventing them. Therefore, an existing need for a composition that is effective against hoof hooves, stable hoof hooves, and PDD, that is capable of being administered, and that avoids the use of antibiotics. There is also a need for an effective method of both controlling and treating hoof hooves, hoof hooves and PDD. There is an additional need for a composition that can be effectively used in leg baths, and can withstand the severe conditions associated with the leg bath. These needs are known by the composition and method of the present invention. It has been surprisingly discovered that an aqueous germicidal composition comprising a copper salt, a quaternary ammonium compound, and a peroxide, is effective in the treatment and prevention of PDD, although none of these germicides has been effectively tested against PDD by itself at any level of use. However, although none of these germicides has been proven effective against PDD individually, in the field trials involving dairy cattle afflicted with PDD, the previous composition was as effective in the treatment of PDD as the use of an antibiotic. In addition, the composition of the present invention is more effective against the irritation of • Hoof and hoof hoof stable than any of the above compounds used individually, and is more able to withstand adverse foot bath conditions. Finally, the present invention also provides a The method for the treatment of infectious diseases of the hooves in animals, which typically comprises applying an effective amount of the above aqueous composition. The composition and method of the present invention • are effective under a wide variety of conditions and dilutions, are cheap to use, and do not have any of the disadvantages associated with the use of antibiotics. The Copper Salt The copper salt of the present invention can be any water soluble copper salt, such as sodium sulfate.

Copper, copper benzoate, copper bicarbonate, copper nitrate, copper nitrite, copper chloride, copper acetate, copper formate, copper trichloroacetate, copper citrate, copper gluconate, and mixtures thereof. Other • Copper salts can be used, as long as the anion is biocidally acceptable and able to solubilize copper cations in water. Preferred copper salts for use in the compositions and methods of the present invention is copper sulfate. Copper salt can be presented in a The amount of about 2% by weight of the composition at • amount in which the composition becomes saturated and the copper salt will no longer dissolve. For copper sulfate, the limit solubility is about 20% copper sulfate by weight of the composition. Preferably, the salt of The copper is present in an amount of about 15% to about 20% by weight of the composition, where the range includes both 15% and 20% of the copper salt contained. Quaternary Ammonium Compound Any quaternary ammonium compound with The germicidal activity can be used in the composition and method of the present invention. Useful quaternary ammonium compounds include alkyl, dialkyl and trialkyl quaternary amino salts, wherein the alkyl groups contain from 1 to 20 carbon atoms in each alkyl group, And quaternary ammonium salts containing one or more substituted or unsubstituted aryl groups, or mixtures of the above quaternary ammonium salts. Quaternary ammonium chlorides are preferred, although other dispersible salts • In water such as acetates, sulfates, nitrates and phosphate, they can also be used. The preferred quaternary ammonium compound in the composition of the present invention is a mixture of N-alkyl (C12-18) -N, N-dimethylbenzylammonium chloride and N-alkyl (C12-18) -N, N- chloride. dimethyl ethylbenzylammonium, which is sold under the tradename BTC 2125 M, and is available from Stepan Company (Norhfield, Illinois). Another quaternary ammonium compound for use in the composition of the present invention is a mixture of N-alkyl (C12-18) N, N-dimethyl-N-benzyl ammonium chloride, N-dodecyl-N, N-dimethyl chloride, N-ethylbenzylammonium, and N-tetradecyl-N, N-dimethyl-N-benzylammonium chloride, which is for sale under the tradename Barquat 4280-Z by Lonza (Fair La n, New Jersey). The quaternary ammonium compound could be • present in an amount of approximately 0.5% a about 2% by weight of the aqueous composition. Preferably, the quaternary ammonium compound may be present in an amount of about 1% to about 2% by weight of the composition. Peroxide Any water-soluble peroxide can be used in the composition and method of the present invention. The preferred peroxide is hydrogen peroxide, and either of the two concentrated or dilute aqueous solutions of hydrogen peroxide can be used. The peroxide could initially be present in an amount of about 0.5% to about 5% by weight in the aqueous compositions of the present invention. Outside the stipulated time, the amount of peroxide in the composition will slowly decrease due to degradation. The preferred range of hydrogen peroxide for the composition of the present invention is from about 1% to about 2% by weight of the composition. General Characteristics The compositions of the present invention could have a pH sufficient to effect the complete dissolution of the copper salt. The pH of the composition could thus be about 3 or less, with a pH of about 1.6 to about 2.0 which is preferred. The aqueous germicidal composition could also be stable under general storage conditions. The viscosity of the composition can be varied depending on the use to make the composition, and it can be made more viscous, if desired, through the use of known thickening agents. Other Components Other components may also be included in the aqueous germicidal compositions of the present invention. For example, agents that adjust the pH can be used to use the pH of the composition at the desired levels. Both mineral acids, organic acids, and mixtures thereof can be used for this purpose. Useful organic acids include hydroxyacetic acid, citric acid, and lactic acid, while mineral acids may be used including phosphoric acid, sulfuric acid and hydrochloric acid. The use of an organic acid or a mixture of an organic acid and a mineral acid is preferred, because it is believed that the peroxide can form a "per-acid" biocide with the organic acid. The amount of the present agent that adjusts the pH is depending on the desired pH. Generally, for the agent adjusting the pH it should be present in an amount of from about 0.5% to about 2.0% by weight of the composition. The aqueous compositions of the present invention may also contain a pH control agent or buffer, to ensure that the components of the composition remain soluble throughout the shelf life of the composition. Organic bases such as amines can be used, such as inorganic bases, such as sodium hydroxide and potassium hydroxide. Typically, the pH control agent is present in an amount of about 0 to about 3% by weight of the composition. The optimal amount will vary depending on the specific components of • the composition. The composition of the present invention may also comprise other additives, which may be any substance that improves the composition with respect to (i) improved solubility or dispersion of other components, (ii) improved adhesion of the composition to the hoof area infected, (iii) control of moisture characteristics, and (iv) improved stability, which can be related to such properties as surface tension and viscosity, among other properties. The composition of the present invention may also comprise colorants, for provide a composition that is visible when applied, to ensure proper and complete application. The composition may comprise agents, such as emollients, which act to decrease skin irritation caused by topical application. Method The present invention includes a method for the prevention or treatment of infectious hoof diseases in animals, which comprises typically administering the aqueous composition of the present invention at or near the infected area. Preferably, the composition is used to treat PDD. The composition can be applied by pouring, pressure release, unloading, sponge cleaning, or spraying on or near the infected area, or by incorporation into a leg wrap. In a preferred embodiment, the composition of the present invention is applied by spraying. Alternatively, the hoof of the animal may be soaked, submerged or sunk in the compositions claimed for treatment effect. For control and prevention of PDD, hoof hoof g ^ 10 and hoof stable hoof, the compositions can be used in a foot bath through which the animal walks. Typically, the composition could be diluted with additional water; however, the composition may not be diluted to such an extent that its germicidal capacity may be reasonably and easily overcome by severe environmental conditions to which a foot bath is subjected such as the presence of faeces in the bath. For use in a leg bath, the compositions of the present invention • can be diluted with water up to approximately 1000 times Preferably, a dilution of 200 kisses was used. Manufacturing The aqueous germicidal composition of the present invention can be manufactured by conventional means. Preferably, the quaternary ammonium compound is added before the addition of the copper salt, and the peroxide may not be added until the copper salt is completely dissolved. After all the components are added, the composition could be mixed for an additional period of time to ensure complete dilution of the copper salt and to achieve an acceptable homogeneity. The present invention is illustrated by the following Examples. These examples are illustrative of the aqueous germicidal compositions and methods of the present invention and not to be construed as limitations on the scope of the invention. EXAMPLE 1 The aqueous composition of Example 1 was made by mixing the components in the following order: Material% by weight Water 69. 9% Hydroxyacetic acid 0. 5% Barlox 12 (surfactant) 1. 0% BTC 2125M (quaternary) 1. 0% 75% phosphoric acid 0. 6% sulfate Pentahydrate of 20. 0% copper 35% hydrogen peroxide "10.0% Total: 100% The previous composition had a pH in the range of 1.6 to 2.0, and a viscosity of 7.0 centipoise.

EXAMPLE 2 The aqueous composition of Example 2 can be made by mixing the components in the following order: • Raw Material% by weight Water 76.1% Natrosol 250 MR-CS 0. 2% 50% NaOH 0. 1% BTC 2125M 1 0% Barlox 12, 30% 1. 0% Hydroxyacetic acid 0. 5% • 75% phosphoric acid 1. 0% Copper pentahydrosulfate 15 .0% 35% hydrogen peroxide 5. 0% FD &C Blue # 1 0. 1% Total: 100% The previous composition had a pH in the range of 5 1.6 to 2.0, a viscosity of 4-6 centipoise, and was extremely stable in storage. EXAMPLE 3 The composition of Example 1 was then tested in the field with dairy cows infected with PDD. A total of 10 of 66 cows that have PDD at various levels of severity were treated with any of the compositions of Example 1, or other commercially available compositions, using oxytetracycline as a positive control, and water as a negative control. Before starting the treatment, each cow was evaluated with respect to the size of the lesion, location of the lesion, appearance of the lesion, dermatitis and • pain. The compositions were sprayed on the infected areas of the hooves during the first week, and once in each of Monday, Wednesday and Friday of the second week. During the two weeks of treatment, and for approximately two weeks, after this, each animal was examined and evaluated with respect to the above factors, ^ 10 An improved percentage of injury was then determined based on the evaluation of the lesion size, and pain with a change in percentage of positive injury that indicates improvement, and a higher positive change that indicates a greater improvement than a minor positive change. The results are shown below in Tables I and II: Table I Two Week Evaluation Two Treatment Group No. of No Pain Sensory Pain% Injury • CH cows. (1) Composition of Example 1 14 12 (86%) * 0 2 (14%) + 68% (2) CuS04 10 1 (10%) 9 (90%) 0 + 6% (3) 27. 5% H202 and 5. 8% peracetic acid 10 0 10 (100%) 0 0% (4) 0.5% CuS04 ionized 11 i (9%: 10 (91%) + 5% (5) Oxi tetracycline • (25mg / ml) 11 10 ( 91%) 0 1 (9%) + 67% (6) Water 10 0 10 (100%) 0 -11% Table II 30 Days of Evaluation Treatment group No. of No pain Pain Sensitive% of Lesion cows CH. (1) Composition of Example 1 13 10 (77%) 1 (8%) 2 (15%) + 74% (2) CuS04 10 2 (20%) 7 (70%) 1 (10%) + 17% ( 3) 27.5% H202 and 5.8% peracetic acid 10 0 10 (100%) 0 0% (4) 0.5% CuS04 ionized 10 0 10 (100%) 0 -5% (5) Oxytetracycline (25mg / ml) 10 8 (80%) 2 (20%) 0 + 68% (6) Water 8 0 8 (100%) 0 -14% The results show that the composition of Example 1 was significantly more effective in PDD treatment than was the case comparative composition, with the exception of oxytetracycline With respect to oxytetracycline, the composition of Example 1 was equally effective in the treatment of PDD EXAMPLE 4 The compositions of Example 1 and Example 2 were tested in the field with dairy cows infected with PDD. A total of 50 cows having PDD at various levels of severity were treated with any of the composition of Example 1, the composition of Example 2, oxytetracycline, a composition comprising 27.5% hydrogen peroxide and 5.8% peracetic acid or water . Oxytetracycline was used as the positive control and water and water was used as the negative control. Before the treatment will begin, each cow was evaluated with respect to injury size, injury color and pain and an initial injury score was calculated. The injury score was calculated by assigning numbers to injury size (0-2), injury color (1-4) and pain (0-2), with a large number indicating a more severe condition. The cows were then divided into test groups, and an average injury score for each test group was calculated. The compositions were sprayed on the infected areas of the hooves once daily during the first week, and once daily for four consecutive days in the second week. Two weeks later the treatment was discontinued, the cows were evaluated with respect to the above factors. An average injury score was determined for each test group, and an improved injury score percentage was determined by subtracting the average post-treatment injury score from the average treatment injury score, dividing that number by the score. of average pretreatment injury. The results are shown in the following Tables III and IV: Table III Treatment group No. of No pain Pain% of Lesions cows CH. • (1) Composition of Example 1 10 10 (100%) + 67! (2) Composition of Example 2 11 ?? (100%: + 65! (3) Oxytetracycline 13 13 (100! + 6 ' (4) 27.5% H202 and • 5.8% acid: (100%; -6th peracetic (5) Water 100! Table IV Average Injury Point Treatment group No. of cows Pre-treatment Post-treatment (1) Composition 10 6 2 of Example 1 (2) Composition of Example 2 11 6 2.09 (3) Oxytetracycline 13 6 2.15 (4) 7.5% H202 and • 5.8% acid 8 5.88 6.25 peracetic (5) Water 8 5.88 6.38 The results show that the compositions of Example 1 and Example 2 were as effective as oxytetracycline in PDD treatment, and were considerably more effective than the peroxide / peracetic acid composition or the negative control (water). • EXAMPLE 5 The composition of Example 1 was tested against commercially available compositions to determine its effectiveness against Fusobactrium necrophum, a bacterium that causes hoof hooves. The compositions were first tested in undiluted form against a predetermined concentration of the bacterium, both in a tube and in a test plate. The compositions were then assayed in an increasingly diluted form, until the point that was reached where the diluted composition does not greatly inhibit bacterial growth. That point is called the minimum inhibitory concentration or "MIC", and is given as a number, N, where N-l represents the number of duplicate dilutions that were made before the composition will fail to inhibit bacterial growth. For example, a MIC of 4 means that three duplicate dilutions were made, in such a way that the final dilution was 1: 8. From • this form, the dilution corresponding to the MIC is given by the formula D = 2N ~ 1, where D is the dilution amount and N is the MIC number. As stated in the above, the compositions were attached to a test tube and to a test plate. The test tube is considered to be more accurate and standardized, while the test plate more exactly emulates the conditions of high organic load found in a leg bath. • The results against Fusubacterium necrophorom are set forth in the following in Table V, with a composition having a higher MIC number that has more germicidal efficacy in the test than a composition having a lower MIC number. The number in parentheses indicates the number of times a particular trial was run.

Table V Composition Test Tiubo MIC Test Plate MIC Example 1 14 (3) 13 (3) • Example 2 12 (1) 0.5% ionized copper sulphate 7 (2) 7 (1) 27.5% hydrogen peroxide 5.8 % peracetic acid 12 (3) 11 (2) Quaternary ammonium compound and testosterone 13 (1) amphoteric Zinc Sulfate 4 (1) Limonene and surfactant 4 (1) 5% copper sulfate 12 (1) 10 (1) 5% copper sulfate in granules 8 (1) 7 (3) 5% paraformaldehyde 4 (1) Lincomycin 11 (1) EXAMPLE 6 The tests in Example 4 were repeated against Dichelobacter nodosus, an organism believed to cause morriña of hoof and hoof of stable hoof. The results are shown in the following Table VI. Table VI Composition MIC Test Tube MIC Assay Plate Example 1 14 (1) 13 (3) 0.5% ionized copper sulfate 5 (1) 27.5% hydrogen peroxide 5.8% '8 (1) peracetic acid Quaternary ammonium compound and surfactants 14.5 (1) amphoteric 5% paraformaldehyde 12 (3) 2 (1)

Claims (29)

1. CLAIMS 1. An aqueous germicidal composition for the treatment or prevention of infectious diseases of the hooves in animals, characterized in that it comprises a copper salt, a quaternary ammonium compound and a peroxide.
2. 2. The composition according to claim 1, characterized in that the pH of the composition is less than about 3.
3. The composition according to claim 1, characterized in that the copper salt is present in an amount of about 2. % to about 20% by weight of the solution, the quaternary ammonium compound is present in an amount of about 0.5 to about 2% by weight of the composition, and the peroxide is present in an amount of about 0.5% to about 5% by weight of the composition.
4. The composition according to claim 3, characterized in that the copper salt is present in an amount of about 15% to about 20% by weight of the composition, the quaternary ammonium compound is present in an amount of about 1% to about 2% by weight of the composition, and the peroxide is present in an amount of about 1% to about 4% by weight of the composition.
5. 5. Composition in accordance with • claim 1, characterized in that the copper salt is 5 copper sulfate.
6. 6. The composition according to claim 5, characterized in that the quaternary ammonium compound is in at least one of the trialkyl benzyl ammonium chlorides, where the benzyl group can be substituted or 10 unsubstituted. #
7. 7. The composition according to claim 6, characterized in that the peroxide is hydrogen peroxide.
8. 8. The composition according to claim 1, further characterized in that it comprises an agent that adjusts the pH.
9. 9. The composition according to claim 8, further characterized in that it comprises a pH control agent.
10. 10. The composition according to claim 9, further characterized in that it comprises a surfactant.
11. 11. The composition according to claim 10, further characterized in that it comprises a 25 agent that improves the viscosity.
12. 12. An aqueous germicidal composition for the treatment or prevention of infectious diseases of the hooves in animals, comprising (a) from about 15% to about 20% copper sulfate by weight of the 5) composition, (b) from about 0.5 to about 2% by weight of the composition of a quaternary ammonium compound comprising at least one trialkyl benzyl ammonium chloride, wherein the benzyl group can be substituted or unsubstituted, and (c) from about 1% to about 10% hydrogen peroxide by weight of the # composition wherein the pH of the composition is less than about 3.
13. 13. A method for treating or preventing infectious diseases of the hooves in animals, comprising 15 administering topically an effective amount of an aqueous germicidal composition comprising a copper salt, a quaternary ammonium compound, and a peroxide.
14. 14. The method according to the claim • 13, characterized because the disease is digital dermatitis 20 papillomatous.
15. 15. The method according to claim 13, characterized in that the copper salt is present in an amount from about 2% to about 20% by weight of the composition, the quaternary ammonium compound is 25 present in an amount of about 0.5% to about 2% by weight of the composition, and the peroxide is present in an amount of about 0.5% a? about 5% by weight of the composition.
16. 16. The method according to claim 5, characterized in that the disease is papillomatous digital dermatitis.
17. 17. The method according to claim 15, characterized in that the disease is hoarseness of the hoof.
18. 18. The method according to claim ^? 10 15, characterized in that the disease is hoarseness of a stable hoof.
19. 19. The method according to claim 13, characterized in that the copper salt is a copper sulfate, the quaternary ammonium compound comprises at least 15 a trialkyl benzyl ammonium chloride, wherein the benzyl group is substituted or unsubstituted, and the peroxide is hydrogen peroxide.
20. 20. The method of compliance with the claim • 13, characterized in that the copper salt is present in a The amount of about 15% to about 20% by weight of the composition, the quaternary ammonium compound is present in an amount of about 1% to about 2% by weight of the composition, and the peroxide is present in an amount of about 1% a 25 about 4% by weight of the composition.
21. 21. The method according to claim 20, characterized in that the disease is papillomatous digital dermatitis.
22. 22. The method according to claim 20, characterized in that the disease is hoarseness of the hoof.
23. 23. The method according to claim 20, characterized in that the disease is hoarseness of a stable hoof.
24. 24. The method according to claim 13, characterized in that the composition is administered as a spray.
25. 25. The method according to claim 13, characterized in that the composition is administered as a leg bath.
26. 26. A method for treating or preventing infectious diseases of the hooves in animals, comprising topically administering an effective amount of an aqueous germicidal composition comprising (a) from about 15% to about 20% copper sulfate by weight of the composition , (b) from about 0.5% to about 2% by weight of the composition of a quaternary ammonium compound comprising at least one trialkyl benzyl ammonium chloride, wherein the benzyl group can be substituted or unsubstituted, and (c) about 1% to about 4% hydrogen peroxide by weight of the composition, wherein the pH of the composition is less than about 3.
27. 27. The method according to claim 26, characterized in that the disease is PDD.
28. 28. The method according to claim 26, characterized in that the disease is hoarseness of the hoof.
29. 29. The method according to claim 26, characterized in that the disease is hoarseness of a stable hoof.