COMPOSITIONS COMPRISING AN ARYL PYRAZOLE AND/OR A FORMAMIDINE, METHODS AND USES THEREOF

• US 20100125097A1
• Filed: 11/13/2009
• Published: 05/20/2010
• Est. Priority Date: 11/19/2008
• Status: Active Grant

• Current Assignee: Merial Incorporated (C.H. Boehringer Sohn AG & Co. KG)
• Original Assignee: Merial Limited (C.H. Boehringer Sohn AG & Co. KG)
• Inventors: Shub, Natalya, Wurtz, Patrice, Pate, James, Cramer, Luiz Gustavo, Soll, Mark David, Timmons, Philip Reid, Le Hir de Fallois, Loic Patrick
• Granted Patent: US 8,450,357 B2
• Time in Patent Office: Days
• US Class Current: 514/407
• CPC Class Codes: A01N 2300/00 Combinations or mixtures of active ingredients covered by classes A01N27/00 - A01N65/48 with other active or formulation relevant ingredients, e.g. specific carrier materials or surfactants, covered by classes A01N25/00 - A01N65/48
• CPC Class Codes: A01N 25/02 containing liquids as carriers, diluents or solvents
• CPC Class Codes: A01N 37/52 containing groups, e.g. carboxylic acid amidines
• CPC Class Codes: A01N 43/36 five-membered rings
• CPC Class Codes: A01N 43/56 1,2-Diazoles; Hydrogenated 1,2-diazoles
• CPC Class Codes: A01N 47/02 the carbon atom having no bond to a nitrogen atom
• CPC Class Codes: A61D 7/00 Devices or methods for introducing solid, liquid, or gaseous remedies or other materials into or onto the bodies of animals for reproduction or fertilisation A61D19/00 ; devices for implanting pellets, radon seeds or the like A61M37/0069
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/155 Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
• CPC Class Codes: A61K 31/231 having one or two double bonds
• CPC Class Codes: A61K 31/415 1,2-Diazoles
• CPC Class Codes: A61K 31/4439 containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole nicotine A61K31/465
• CPC Class Codes: A61K 47/08 containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
• CPC Class Codes: A61K 47/14 Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
• CPC Class Codes: A61K 9/0017 Non-human animal skin, e.g. pour-on, spot-on
• CPC Class Codes: A61P 33/00 Antiparasitic agents
• CPC Class Codes: A61P 33/10 Anthelmintics
• CPC Class Codes: A61P 33/14 Ectoparasiticides, e.g. scabicides
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

This invention relates to compositions for combating parasites in animals, comprising 1-arylpyrazole compounds alone or in combination with formamidine compounds. This invention also provides for an improved methods for eradicating, controlling, and preventing parasite infestation in an animal comprising administering the compositions of the invention to the animal in need thereof.

Claims

1. A veterinary formulation for treating or preventing a parasitic infestation in an animal comprising:

(a) a 1-aryl-5-alkyl or 5-haloalkylpyrazole of formula (IA) or a veterinarily acceptable salt thereof,

2. A composition for the treatment or prevention of a parasitic infestation in an animal comprising at least one 1-arylpyrazole compound in a first veterinarily acceptable carrier, at least one formamidine compound in a second veterinarily acceptable carrier, and optionally at least one crystallization inhibitor, wherein the 1-arylpyrazole compound(s) and first veterinarily acceptable carrier are compartmentalized together, and not in fluid communication with, the formamidine compound(s) and the second veterinarily acceptable carrier.

3. The composition of claim 2, wherein the 1-arylpyrazole compound(s) and the first veterinarily acceptable carrier are in one cavity of a dual-cavity container and the formamidine compound(s) and the second veterinarily acceptable carrier are in a second cavity of a dual-cavity container, wherein the first cavity is defined by a front wall and a divider wall;

and the second cavity is defined by a rear wall and the divider wall.

4. The composition of claim 2, wherein at least one 1-arylpyrazole compound has formula (IB):

5. The composition of claim 4, wherein:

R_1b is methyl, CN or halogen;

R_2b is S(O)_nR_14b;

R_14b is C₁-C₆-alkyl or C₁-C₆-haloalkyl;

R_3b is —

NR_7bR_8b,

R_7b and R_8b independently represent a hydrogen, C₁-C₆-alkyl, C₁-C₆-haloalkyl, —

C(O)C₁-C₆-alkyl, —

S(O)_rCF₃, C₁-C₆-acyl or C₁-C₆-alkoxycarbonyl radical;

R_6b is a halogen, C₁-C₆-haloalkyl, or C₁-C₆-haloalkoxy;

m, n, q and r represent, independently of one another, an integer equal to 0 or 1; and

Z is a C—

R_13b radical.

6. The composition of claim 4, wherein:

R_1b is methyl, CN or halogen;

R_2b is S(O)_nR_14b;

R_14b is C₁-C₆-alkyl or C₁-C₆-haloalkyl;

R_3b is alkyl or haloalkyl;

R_6b is a halogen, C₁-C₆-haloalkyl, or C₁-C₆-haloalkoxy;

m, n, q and r represent, independently of one another, an integer equal to 0 or 1; and

Z is a C—

R_13b radical.

7. The composition of claim 2, wherein the first veterinarily acceptable carrier comprises acetone, acetonitrile, benzyl alcohol, ethanol, isopropanol, diisobutyl adipate, diisopropyl adipate, butyl diglycol, dipropylene glycol n-butyl ether, ethylene glycol monoethyl ether, ethylene glycol monomethyl ether, dipropylene glycol monomethyl ether, liquid polyoxyethylene glycols, propylene glycol monomethyl ether, propylene glycol monoethyl ether, 2-pyrrolidone, N-methylpyrrolidone, diethylene glycol monoethyl ether, triacetin, butyl acetate, octyl acetate, propylene carbonate, butylene carbonate, dimethyl sulfoxide, an amide, dimethylformamide, dimethylacetamide, or any combination thereof.

8. The composition of claim 2, wherein the second veterinarily acceptable carrier comprises aryl ethers, alkoxybenzene compounds, aliphatic carboxylic acid esters, aromatic carboxylic acid esters, aliphatic ketones, cyclic ketones, or mixtures thereof.

9. The composition of claim 2, wherein the second veterinarily acceptable carrier comprises methoxybenzene, butyl acetate, benzyl acetate, methyl isobutyl ketone, ethyl benzoate, benzyl benzoate, octyl acetate, or mixtures thereof.

10. The composition of claim 2, wherein the second veterinarily acceptable carrier comprises an aprotic solvent with a dielectric constant of about 2 to about 30.

20. A method for the treatment or prevention of a parasitic infestation in an animal comprising administering an effective amount of the composition of claim 2 to the animal.

21. The method of claim 20, wherein at least one 1-arylpyrazole compound is fipronil.

22. The method of claim 20, wherein at least one formamidine compound is amitraz.

23. The method of claim 20, wherein the composition is administered using a dual-cavity container, wherein the 1-arylpyrazole compound(s) and the first veterinarily acceptable carrier are administered from a first cavity of the dual-cavity container and the formamidine compound(s) and the second veterinarily acceptable carrier are administered from a second cavity of the dual-cavity container.

24. The method of claim 22, wherein the 1-arylpyrazole compound(s) and the formamidine compound(s) are administered simultaneously.

11. A composition for the treatment and prevention of a parasitic infestation in an animal comprising at least one formamidine compound;

at least one 1-arylpyrazole compound of formula (IA), or veterinarily acceptable salts thereof,

12. The composition of claim 2 or 11, wherein at least one formamidine compound has the formula (II):

13. The composition of claim 2 or 11, wherein at least one formamidine compound is amitraz, formetanate, chloromebuform, formparanate or chlodimeform.

14. The composition of claim 11, wherein the 1-arylpyrazole compound(s) is combined with a first veterinarily acceptable carrier and the formamidine compound(s) is combined with a second veterinarily acceptable carrier;

and wherein the 1-arylpyrazole compound(s) and the first veterinarily acceptable carrier are compartmentalized together, and not in fluid communication with, the formamidine compound(s) and the second veterinarily acceptable carrier.

25. A method for the treatment or prevention of a parasitic infestation in an animal comprising administering an effective amount of the composition of claim 11 to the animal.

26. The method of claim 25, wherein the 1-arylpyrazole compound(s) is in a first veterinarily acceptable carrier, and the formamidine compound(s) is in a second veterinarily acceptable carrier;

wherein the 1-arylpyrazole compound(s) and first veterinarily acceptable carrier are compartmentalized together, and not in fluid communication with, the formamidine compound(s) and the second veterinarily acceptable carrier.

27. The method of claim 26, wherein the 1-arylpyrazole compound(s) and the formamidine compound(s) are administered simultaneously.

28. The method of claim 25, wherein at least one formamidine compound is amitraz.

15. A composition for the treatment and prevention of a parasitic infestation in an animal comprising at least one formamidine compound and at least one aprotic solvent with a dielectric constant of about 2 to about 30, wherein the composition is stable for at least 24 months at 25°

C.

16. The composition of claim 15, wherein at least one formamidine compound is amitraz.

17. The composition of claim 15, wherein the aprotic solvent(s) with a dielectric constant of about 2 to about 30 has a water content of less than about 0.05% (w/w).

18. The composition of claim 15, wherein the aprotic solvent(s) with a dielectric constant of about 2 to about 30 is a C₁-C₁₀ carboxylic acid ester, a phenyl carboxylic acid ester, a carboxylic acid benzyl ester, a benzoic acid C₁-C₄ alkyl ester, a C₁-C₆ saturated aliphatic ketone, or a mixture thereof.

19. The composition of claim 15, comprising at least two aprotic solvents with a dielectric constant of about 2 to about 30, wherein a dissipation of an unpleasant odor from the composition occurs within about 5 minutes to within about 25 minutes after application.

29. A method for the treatment or prevention of a parasitic infestation in an animal comprising administering to the animal an effective amount of a composition comprising at least one 1-arylpyrazole compound in a first veterinarily acceptable carrier and at least one formamidine compound in a second veterinarily acceptable carrier from a dual-cavity container;

wherein the 1-arylpyrazole compound(s) and the first veterinarily acceptable carrier are in one cavity of the dual-cavity container and the formamidine compound(s) and the second veterinarily acceptable carrier are in a second cavity of the dual-cavity container; and

wherein the first cavity is defined by a front wall and a divider wall, and the second cavity is defined by a rear wall and the divider wall.

30. The method of claim 29, wherein at least one 1-arylpyrazole compound is fipronil.

31. The method of claim 29, wherein the at least one 1-arylpyrazole compound is 3-cyano-1-(2-chloro-6-fluoro-4-trifluoromethylphenyl)-4-dichlorofluoromethylsulfinyl-5-methyl-1H-pyrazole.

32. The method of claim 29, wherein at least one formamidine compound is amitraz.

33. The method of claim 29, wherein the 1-arylpyrazole compound(s) and the formamidine compound(s) are administered simultaneously.

34. A kit for the treatment or prevention of a parasitic infestation in an animal, comprising:

at least one 1-arylpyrazole compound in a first veterinarily acceptable carrier, at least one formamidine compound in a second veterinarily acceptable carrier, and a multiple-cavity container;

wherein the 1-arylpyrazole compound(s) in a first veterinarily acceptable carrier is in a first cavity of the multiple-cavity container and the formamidine compound(s) in a second veterinarily acceptable carrier is in a second cavity of the multiple-cavity container; and

wherein the first cavity is defined by a front wall and a divider wall, and the second cavity is defined by a rear wall and the divider wall.