Topical Localized Isoxazoline Formulation

1 . A topical localized formulation for the treatment or prophylaxis of parasite infestation in animals which comprises an effective amount of at least one isoxazoline compound of the Formula (I)

wherein

R 1 =halogen, CF 3 , OCF 3 , CN,

n=integer from 0 to 3, preferably 1, 2 or 3,

R 2 =C 1 -C 3 -haloalkyl,

T=5- or 6-membered ring, which is optionally substituted by one or more radicals Y,

Y=methyl, halomethyl, halogen, CN, NO 2 , NH 2 —C═S, or two adjacent radicals Y form together a chain CH—CH═CH—CH, N—CH═CH—CH, CH—N═CH—CH, CH—CH═N—CH, or CH—CH═CH—N, HC═HC—CH, CH—CH═CH, CH═CH—N, N—CH═CH

Q=X—NR 3 R 4 or a 5-membered N-heteroaryl ring, which is optionally substituted by one or more radicals;

X=CH 2 , CH(CH 3 ), CH(CN), CO, CS,

R 3 =hydrogen, methyl, haloethyl, halopropyl, halobutyl, methoxymethyl, methoxyethyl, halomethoxymethyl, ethoxymethyl, haloethoxymethyl, propoxymethyl, ethylaminocarbonylmethyl, ethylaminocarbonylethyl, dimethoxyethyl, propynylaminocarbonylmethyl, N-phenyl-N-methyl-amino, haloethylaminocarbonylmethyl, haloethylaminocarbonylethyl, tetrahydrofuryl, methylaminocarbonylmethyl, (N,N-dimethylamino)-carbonylmethyl, propylaminocarbonylmethyl, cyclopropylaminocarbonylmethyl, propenylaminocarbonylmethyl, haloethylaminocarbonylcyclopropyl,

wherein Z A =hydrogen, halogen, cyano, halomethyl (CF 3 );

R 4 =hydrogen, ethyl, methoxymethyl, halomethoxymethyl, ethoxymethyl, haloethoxymethyl, propoxymethyl, methylcarbonyl, ethylcarbonyl, propylcarbonyl, cyclopropylcarbonyl, methoxycarbonyl, methoxymethylcarbonyl, am inocarbonyl, ethylaminocarbonylmethyl, ethylaminocarbonylethyl, dimethoxyethyl, propynylaminocarbonylmethyl, haloethylaminocarbonylmethyl, cyanomethylaminocarbonylmethyl, or haloethylaminocarbonylethyl;

Or R 3 and R 4 together form a substituent selected from the group consisting of:

and a veterinary acceptable liquid carrier vehicle wherein the liquid carrier vehicle comprises N,N-diethyl-3-methylbenzamide as a solvent.

2 . The topical localized formulation according to claim 1 , wherein the isoxazoline compound is a compound of formula II

wherein

R 1a , R 1b , R 1c are independently from each other hydrogen, Cl or CF 3 ,

T=

wherein Y is methyl, bromine, Cl, F, CN or C(S)NH 2 .

3 . The topical localized formulation according to claim 1 , wherein R 3 is H and R 4 is —CH 2 —C(O)—NH—CH 2 —CF 3 , —CH 2 —C(O)—NH—CH 2 —CH 3 , —CH 2 —CH 2 —CF 3 or —CH 2 —CF 3 .

4 . (canceled)

5 . The topical localized formulation according to claim 1 , wherein the formulation comprises 1 to 50% N,N-diethyl-3-methylbenzamide.

6 . The topical localized formulation according to claim 1 , wherein the liquid carrier vehicle comprises N,N-diethyl-3-methylbenzamide as solvent and a co-solvent selected from the group consisting of dimethyl sulfoxide, acetone, dimethylacetamide, ethyl alcohol, eucalyptol, dipropylene glycol monomethyl ether, methylethyl ketone, glycofurol, ethyl-L-lactate, and a mixture of at least two of these co-solvents.

7 . The topical localized formulation according to claim 6 wherein the liquid carrier vehicle comprises N,N-diethyl-3-methylbenzamide as solvent and a mixture of at least two of acetone, ethyl-L-lactate, dimethyl sulfoxide, dimethylacetamide and glycofurol.

8 . The topical localized formulation according to claim 6 wherein there is a weight/weight ratio of the cosolvent/solvent in the spot-on composition and the weight/weight ratio of the cosolvent/solvent is between 4/1 and 1/5.

9 . The topical localized formulation according to claim 1 , wherein the formulation further comprises an effective amount of one or more compounds selected from a macrocyclic lactone compound or an insect growth regulator compound.

10 . (canceled)

11 . A method for treatment or prophylaxis of parasite infestation of an animal comprising spot-on or pour-on administration of a localized topical formulation of claim 1 .

12 . (canceled)

13 . The method of claim 11 wherein the veterinary acceptable liquid carrier comprises a co-solvent of at least two of acetone, ethyl-L-lactate, dimethyl sulfoxide, dimethylacetamide and glycofurol.

14 . The method of claim 11 wherein the topical localized formulation comprises additionally an effective amount of a macrocyclic lactone compound and/or an insect growth regulator compound.

15 . The method of claim 14 wherein the macrocyclic lactone compound is selected from ivermectin, moxidectin, milbemycin, selamectin, emamectin, latidectin and lepimectin or a salt thereof and the insect growth regulator compound is selected from fenoxycarb, lufenuron, diflubenzuron, novaluron, triflumuron, fluazuron, cyromazine, methoprene and pyriproxyfen.

16 . The topical localized formulation of claim 1 , wherein the liquid carrier vehicle comprises N,N-diethyl-3-methylbenzamide as solvent and a co-solvent selected from the group consisting of dimethyl sulfoxide, dimethylacetamide, ethyl alcohol, eucalyptol, dipropylene glycol monomethyl ether, methylethyl ketone, glycofurol, ethyl-L-lactate, and a mixture of at least two of these co-solvents.

17 . The topical localized formulation of claim 16 , wherein the formulation further comprises an effective amount of one of more compounds selected from a macrocyclic lactone compound or an insect growth regulator compound.

18 . The topical localized formulation of claim 17 , wherein the macrocyclic lactone compound is selected from ivermectin, moxidectin, milbemycin, selamectin, emamectin, latidectin and lepimectin or a salt thereof and the insect growth regulator compound is selected from fenoxycarb, lufenuron, diflubenzuron, novaluron, triflumuron, fluazuron, cyromazine, methoprene and pyriproxyfen.

19 . The method of claim 13 , wherein the veterinary acceptable liquid carrier comprises a co-solvent of at least two of ethyl-L-lactate, dimethyl sulfoxide, dimethylacetamide and glycofurol.

20 . The topical localized formulation of claim 1 , wherein R 2 is CF 3 or CF 2 Cl.

21 . The topical localized formulation of claim 2 , wherein R 1a and R 1c are Cl and R 1b is hydrogen,