PARASITICIDAL COMPOSITIONS COMPRISING AN ISOXAZOLINE ACTIVE AGENT, METHODS AND USES THEREOF

• US 20130065846A1
• Filed: 09/12/2012
• Published: 03/14/2013
• Est. Priority Date: 09/12/2011
• Status: Active Grant

• Current Assignee: Merial Incorporated (C.H. Boehringer Sohn AG & Co. KG)
• Original Assignee: Joseph K. Rosentel Jr
• Inventors: Soll, Mark D., Pate, James, Shub, Natalya, Rosentel, Joseph K. Jr., Motwani-Tejwani, Monica, Belansky, Carol
• Granted Patent: US 9,180,121 B2
• Time in Patent Office: Days
• US Class Current: 514/30
• CPC Class Codes: A01N 43/40 six-membered rings
• CPC Class Codes: A01N 43/80 five-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,2
• CPC Class Codes: A01N 49/00 Biocides, pest repellants or attractants, or plant growth regulators, containing compounds containing the group , wherein m+n>=1, both X together may also mean —Y— or a direct carbon-to-carbon bond, and the carbon atoms marked with an asterisk are not part of any ring system other than that which may be formed by the atoms X, the carbon atoms in square brackets being part of any acyclic or cyclic structure, or the group , wherein A means a carbon atom or Y, n>=0, and not more than one of these carbon atoms being a member of the same ring system, e.g. juvenile insect hormones or mimics thereof containing hydrocarbons A01N27/00
• 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 31/215 of carboxylic acids
• CPC Class Codes: A61K 31/22 of acyclic acids, e.g. pravastatin
• CPC Class Codes: A61K 31/231 having one or two double bonds
• CPC Class Codes: A61K 31/366 having six-membered rings, e.g. delta-lactones
• CPC Class Codes: A61K 31/415 1,2-Diazoles
• CPC Class Codes: A61K 31/42 Oxazoles
• CPC Class Codes: A61K 31/44 Non condensed pyridines; Hydrogenated derivatives thereof
• CPC Class Codes: A61K 31/4402 only substituted in position 2, e.g. pheniramine, bisacodyl
• CPC Class Codes: A61K 31/4745 condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines yohimbine derivatives, vinblastine A61K31/475; ergoline derivatives A61K31/48
• CPC Class Codes: A61K 31/7048 having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin , digitoxin or digoxin
• CPC Class Codes: A61K 38/15 Depsipeptides; Derivatives thereof
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 47/08 containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• 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 47/22 Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
• CPC Class Codes: A61K 47/26 : Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
• CPC Class Codes: A61K 9/0017 : Non-human animal skin, e.g. pour-on, spot-on
• CPC Class Codes: A61K 9/06 : Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels composition of ointments, creams or gels A61K47/00
• 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 topical compositions for combating ectoparasites and endoparasites in animals, comprising at least one isoxazoline active agent and a pharmaceutically acceptable carrier, optionally in combination with one or more additional active agents. This invention also provides for an improved methods for eradicating, controlling, and preventing parasite infections and infestations in an animal comprising administering the compositions of the invention to the animal in need thereof.

Claims

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

a) at least one isoxazoline active agent of Formula (I);

2. The topical veterinary composition of claim 1, wherein:

W is O;

R⁴ is H or C₁-C₆ alkyl;

R⁵ is —

CH₂C(O)NHCH₂CF₃;

each of A¹, A², A³, A⁴, A⁵ and A⁶ is CH;

R¹ is C₁-C₆ alkyl each optionally substituted with one or more substituents independently selected from R⁶;

R⁶ is halogen or C₁-C₆ alkyl; and

B¹, B², and B³ are independently CH, C-halogen, C—

C₁-C₆ alkyl, C—

C₁-C₆ haloalkyl, or C—

C₁-C₆ alkoxy.

3. The topical veterinary composition of claim 1, wherein:

W is O;

R¹ is CF₃;

B² is CH;

B¹ is chloro;

B³ is CF₃;

each of A¹, A², A³, A⁴, A⁵ and A⁶ is CH;

R⁴ is H; and

R⁵ is —

CH₂C(O)NHCH₂CF₃.

4. The topical veterinary composition of claim 1, wherein the pharmaceutically acceptable carrier comprises a diester of a dicarboxylic acid, a glycol ester, a glycol ether, a fatty acid ester, a polyethylene glycol, or polyethylene glycol ester, an oil, an alcohol, a glycerol ester, a glycerol ether, propylene glycol, ethylene glycol, a glycol carbonate, dimethyl isosorbide, N-methylpyrrolidone, or a mixture thereof.

5. The topical veterinary composition of claim 4, wherein the diester of a dicarboxylic acid is a diester of a C₆-C₁₆ dicarboxylic acid.

6. The topical veterinary composition of claim 5, wherein the diester of a C₆-C₁₆ dicarboxylic acid is diethyl sebacate or diisopropyl adipate.

7. The topical veterinary composition of claim 4, wherein the pharmaceutically acceptable carrier comprises mixture of a diester of a dicarboxylic acid and a propylene glycol ester, a fatty acid ester, a polyethylene glycol ester, a polyethylene glycol, an oil, a C₆-C₂₀ long-chain aliphatic alcohol, a C₁-C₈ alcohol, glycol ether, or a combination thereof.

8. The topical veterinary composition of claim 4, wherein the pharmaceutically acceptable carrier comprises a mixture of a diester of a dicarboxylic acid and further comprises a mixed ester of sucrose and acetic and isobutyric acid, a low melting wax, a hard fat or a block co-polymer of ethylene oxide and propylene oxide, or a combination thereof.

9. The topical veterinary composition of claim 4, wherein the pharmaceutically acceptable carrier comprises dimethyl isosorbide, glycerol formal, propylene carbonate, triacetin, diethyleneglycol monoethyl ether, polyethylene glycol 400 or benzyl alcohol, or a mixture thereof.

10. The topical veterinary composition of claim 1, further comprising at least a second active agent.

11. The topical veterinary composition of claim 10, wherein the at least second active agent is an insect growth regulator, a neonicotinoid or an avermectin or milbemycin.

12. The topical veterinary composition of claim 11, wherein the isoxazoline active agent is 4-[5-[3-chloro-5-(trifluoromethyl)phenyl]-4,5-dihydro-5-(trifluoromethyl)-3-isoxazolyl]-N-[2-oxo-2-[(2,2,2-trifluoroethyl)amino]ethyl]-1-naphthalanecarboxamide and the neonicotinoid is nitenpyram.

13. The topical veterinary composition of claim 11, wherein the at least second active agent is an insect growth regulator.

14. The topical veterinary composition of claim 13, wherein the insect growth regulator is (S)-methoprene, pyriproxyfen, hydroprene, cyromazine, fluazuron, lufenuron, or novaluron.

15. The topical veterinary composition of claim 11, wherein the avermectin or milbemycin is eprinomectin, ivermectin, selamectin, milbemectin, milbemycin D, milbemycin oxime, or moxidectin

16. The topical veterinary composition of claim 10, wherein the at least second active agent is an anthelmintic active agent selected from thiabendazole, oxibendazole, mebendazole, fenbendazole, oxfendazole, albendazole, triclabendazole, febantel, levamisole, pyrantel, morantel, praziquantel, closantel, clorsulon, an amino acetonitrile active agent, or an aryloazol-2-yl cyanoethylamino active agent.

17. The topical veterinary composition of claim 1, wherein the composition is a spot-on composition.

18. The topical veterinary composition of claim 1, wherein the composition is a pour-on composition.

19. A method for the treatment or prevention of a parasitic infestation or infection in an animal comprising administering to the animal an effective amount of the topical veterinary composition of claim 1.

20. The method of claim 19, wherein the isoxazoline is 4-[5-[3-chloro-5-(trifluoromethyl)phenyl]-4,5-dihydro-5-(trifluoromethyl)-3-isoxazolyl]-N-[2-oxo-2-[(2,2,2-trifluoroethyl)amino]ethyl]-1-naphthalenecarboxamide.

21. Use of an isoxazoline of formula (I) in claim 1 in the preparation of a topical veterinary composition for the treatment or protection of an animal against parasites.