Topical formulations comprising 1-N-arylpyrazole derivatives and amitraz
The present invention provides for, inter alia, novel topical formulations comprising at least one 1-N-arypyrazole derivative and amitraz and to methods for treating, controlling, or preventing parasite infestations on mammals or birds The inventive formulations include spot-on, pour-on or spray formulations and may include a further ectoparasiticide, such as an IGR compound, an avermectin or milbemycin derivative, or a pyrethroid insecticides, and anthelmintics, such as benzimidazoles and imidazothiazoles. The inventive formulation provides a larger duration of parasite control at a faster rate of control. The inventive formula remains effective up to three months from the first application. Moreover, the inventive formulations prevent tick attachment to the animal, thereby providing protection against tick borne diseases. The ectoparasites which may be controlled, treated or prevented by the present invention includes ticks, fleas, mites, mange, lice, mosquitoes, flies and cattle grubs.
1. A method for controlling ectoparasites in a mammal or bird in need thereof comprising topically applying an effective amount of a composition comprising an effective amount of an ectoparasiticidal combination of fipronil and amitraz to the mammal or bird.
2. The method of claim 1 , wherein the ectoparasiticidal combination further comprises an insect growth regulator, an avermectin or milbemycin, a pyrethroid, a benzamidazole or an imidazole.
3. The method of claim 2 , wherein the insect growth regulator is a compound that mimics juvenile hormones.
4. The method of claim 3 , wherein the compound that mimics juvenile hormones is azadirchtin, diofenolan, fenoxycarb, hydroprene, kinoprene, methoprene, pyriproxyfen, tetrahydroazadirachtin or 4-chloro-2-(2-chloro-2-methylpyropyl)-5-(6-iodo-3-pyridylmethoxy)pyridazin-3(2H)-one.
5. The method of claim 4 , wherein the compound that mimics juvenile hormones is methoprene or pyriproxyfen.
6. The method of claim 2 , wherein the insect growth regulator is a chitin synthesis inhibitor.
7. The method of claim 6 , wherein the chitin synthesis inhibitor is chlorfluazuron, cyromazine, diflubenzuron, fluazuron, flucycloxuron, flufenoxuron, hexaflumuron, lufenuron, tebufenozide, teflubenzuron, triflumuron, novaluron, 1-(2,6-difluorobenzoyl)-3-(2-fluoro-4-((trifluoromethyl)) phenyl urea, 1-(2,6-difluorobenzoyl)-3-(2-fluoro-4-(1,1,2,2-tetrafluoroethoxy))phenylurea or 1-(2,6-difluorobenzoyl)-3-(2-fluoro-4-trifluoro-methyl)phenylurea.
8. The method of claim 2 , wherein the avermectin or milbemycin is doramectin, emamectin, abamectin, eprinomectin, ivermectin, selamectin, moxidectin or milbemycin oxime.
9. The method of claim 1 , wherein the ectoparasiticidal combination is applied to a localized region on the mammal or bird.
10. The method of claim 9 , wherein the localized region has a surface area of less than 10 cm 2 .
11. The method of claim 1 , wherein the amount of fipronil administered to the mammal or bird is about 0.001 mg to about 100 mg per kg of body weight and the amount of amitraz administered to the mammal or bird is about 0.001 mg to about 100 mg per kg of body weight.
12. The method of claim 1 , wherein the mammal is a cat or a dog, and wherein the volume of the composition applied is about 0.3 to about 1 ml for a cat and about 0.3 to about 5 ml for a dog.
13. The method of claim 1 , wherein the composition is applied monthly to the mammal or bird.
14. The method of claim 1 , wherein the composition is effective for about one month to about three months.
15. The method of claim 1 , wherein the composition is a spot-on formulation.
16. The method of claim 1 , wherein the composition is a pour-on formulation.
17. The method of claim 1 , wherein the composition is a spray formulation.
18. The method of claim 1 , wherein the ectoparasiticidal combination of fipronil and amitraz is in a liquid carrier comprising an organic solvent that has a dielectric constant of about 10 to about 35.
19. The method of claim 1 , wherein the ectoparasiticidal combination of fipronil and amitraz is in a liquid carrier comprising an organic solvent, and wherein the organic solvent is acetone, ethyl acetate, acetonitrile, acetyltributyl citrate, benzyl alcohol, butyldiglycol, dimethylacetamide, dimethylformamide, dipropylene glycol n-butyl ether, dipropylene glycol monomethyl ether, ethylene glycol monomethyl ether, liquid polyoxyethylene glycols, propylene glycol, 2-pyrrolidone, N-methylpyrrolidone, ethyleneglycol monoethyl ether, diethyleneglycol monoethyl ether, ethylene glycol, DMSO, diethyl phthalate, fatty acid esters, diisobutyl adipate, ethanol, isopropanol, or methanol, or a combination thereof.
20. The method of claim 18 , wherein the liquid carrier comprising further comprises an organic co-solvent, and wherein the organic co-solvent has a dielectric constant of between about 10 and about 40.
21. The method of claim 20 , wherein the organic co-solvent is ethanol, isopropanol or methanol.
22. The method of claim 1 , wherein the composition comprises a crystallization inhibitor, and wherein the crystallization inhibitor is polyvinylpyrrolidone, a polyvinyl alcohol, a copolymer of vinyl acetate and vinylpyrrolidone, a polyethylene glycol, benzyl alcohol, mannitol, glycerol, sorbitol, a polyoxyethylenated ester of sorbitan, lecithin, sodium carboxymethylcellulose, an acrylic derivative, an anionic surfactant, a cationic surfactant, an amine salt, a non-ionic surfactant, or an amphoteric surfactant, or a mixture of at least two of these compounds.
23. The method of claim 22 , wherein the crystallization inhibitor is present in a concentration of about 1% (w/v) to about 20% (w/v).
24. The method of claim 21 , wherein the organic solvent is diethyleneglycol monoethyl ether; and the organic co-solvent is ethanol or isopropanol.
25. The method of claim 1 , wherein the composition comprises a combination of fipronil and amitraz in a concentration of from about 1 to about 20% (w/v).
26. The method of claim 1 , wherein composition comprises about 10% (w/v) fipronil and about 12% (w/v) amitraz.
27. The method of claim 1 , wherein composition comprises about 10% (w/v) fipronil and about 15% (w/v) amitraz.
28. The method of claim 11 , wherein the amount of fipronil administered to the mammal or bird is about 0.001 mg to about 10 mg per kg of body weight and the amount of amitraz administered to the mammal or bird is about 0.001 mg to about 10 mg per kg of body weight.
29. The method of claim 22 , wherein the non-ionic surfactant is a polyoxyethylenated ester of sorbitan, a polyoxyethylenated alkyl ether, a polyoxyethylenated derivative of castor oil, a polyoxyethylenated fatty alcohol or a polyoxyethylenated fatty acid.
30. The method of claim 29 , wherein the non-ionic surfactant is Polysorbate 80.