RU2023117591A - INJECTABLE ISOXAZOLINE PHARMACEUTICAL COMPOSITIONS AND THEIR USE - Google Patents

Claims (50)

1. An injectable pharmaceutical composition containing particles of an isoxazoline compound of formula (I) Formula (I), Where R ¹ is halogen, CF ₃ , OCF ₃ or CN; n is an integer from 0 to and including 3, preferably 1, 2 or 3: m is 1 or 2; R ² is C ₁ -C ₃ haloalkyl, CF ₃ or CF ₂ Cl; T is a 5 or 6 membered ring or bicycle which is optionally substituted with one or more Y radicals; Y is methyl, halomethyl, halogen, CN, NO ₂ , NH ₂ -C=S, or two neighboring Y radicals together form a chain; Q is X-NR ³ R ⁴ , NR ⁵ -NR ⁶ -XR ³ , XR ³ or a 5-membered N-heteroaryl ring which is optionally substituted with one or more radicals; X is CH ₂ , CH(CH ₃ ), CH(CN), CO, CS; R ³ is hydrogen, methyl, haloethyl, halopropyl, halobutyl, methoxymethyl, methoxyethyl, halomethoxymethyl, ethoxymethyl, haloethoxymethyl, propoxymethyl, ethylaminocarbonylmethyl, ethylaminocarbonylethyl, dimethoxyethyl, propynylaminocarbonylmethyl, N-phenyl-N-methylamino, haloethylaminocarbonylmethyl, haloethylaminocarbonylethyl, tetrahydrofuryl, methylaminocarbonylmethyl , (N, N-dimethylamino)-carbonylmethyl, propylaminocarbonylmethyl, cyclopropylaminocarbonylmethyl, propenylaminocarbonylmethyl, haloethylaminocarbonylcyclopropyl, alkylsulfanylalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, cycloalkyl,
R3-1 ^_ _
R3-2 ^_ _
R3-3 ^_ _
R3-4 ^_ _
R3-5 ^_ _
R3-6 ^_ _
R3-7 ^_ _
R3-8 ^_ _
R3-9 ^_ _
R3-10 ^_ _
R3-11 ^_ _
R3-12 ^_ _
R3-13 ^_ _
R3-14 ^_ _
R3-15 ^_ _
R3-16 ^_ _ or
R3-17 ^_ _
R3-18 ^_ _ Where Z ^A is hydrogen, halogen, cyano or halomethyl (CF ₃ ); R ⁴ is hydrogen, ethyl, methoxymethyl, halomethoxymethyl, ethoxymethyl, haloethoxymethyl, propoxymethyl, methylcarbonyl, ethylcarbonyl, propylcarbonyl, cyclopropylcarbonyl, methoxycarbonyl, methoxymethylcarbonyl, aminocarbonyl, ethylaminocarbonylmethyl, ethylaminocarbonylethyl, dimethoxyethyl, propylaminocarbonylmethyl, haloethylaminocarbonylmethyl, cyanomethylaminocarbonylmethyl or haloethylaminocarbonylethyl; R ⁵ is H, alkyl or haloalkyl; R ⁶ is H, alkyl or haloalkyl; or where R ³ and R ⁴ together form a substituent selected from the group consisting of: And or a salt or N-oxide thereof and a pharmaceutically acceptable excipient, wherein the isoxazoline compound has a volume-weighted particle size distribution D50, as measured by a static light scattering instrument, of about 25 microns to about 250 microns. 2. An injectable pharmaceutical composition according to claim 1, wherein the isoxazoline compound is present as a suspension in the composition. 3. An injectable pharmaceutical composition according to any one of claims 1 to 2, wherein the particle size distribution D50 is from about 75 microns to about 150 microns. 4. The injectable pharmaceutical composition of claim 3 wherein the D50 particle size distribution is from about 90 microns to about 110 microns. 5. An injectable pharmaceutical composition according to any one of claims 1 to 4, wherein the isoxazoline compound is fluralaner. 6. Injectable pharmaceutical composition according to any one of claims 1 to 5, in which the isoxazoline compound is present in an amount ranging from about 5% wt./about. up to about 50% wt./about. 7. Injectable pharmaceutical composition according to claim 6, in which the isoxazoline compound is present in an amount ranging from about 25% wt./about. up to about 35% wt./about. 8. Injectable pharmaceutical composition according to claim 6, in which the isoxazoline compound is present in an amount in the range from about 5% wt./about. up to about 10% wt./about. 9. An injectable pharmaceutical composition according to any one of claims 1 to 8, wherein the composition is to be reconstituted in a carrier medium. 10. An injectable pharmaceutical composition according to any one of claims 1 to 9, wherein the composition further comprises another parasiticide compound. 11. An injectable pharmaceutical composition according to claim 10, wherein the parasiticide compound is a macrocyclic lactone. 12. An injectable pharmaceutical composition according to claim 11 wherein the macrocyclic lactone compound is selected from moxidectin and milbemycin. 13. An injectable pharmaceutical composition according to claim 12, wherein the parasiticide compound is moxidectin. 14. Injectable pharmaceutical composition according to claim 13, in which moxidectin is presented in an amount in the range from about 0.1% wt./about. up to about 1.0% wt./about. 15. A method of treating or preventing infestation of an animal, comprising administering to an animal in need thereof an effective amount of an injectable pharmaceutical composition according to any one of claims 1-14. 16. The method of claim 15 wherein the animal experiences minimal irritation at the injection site. 17. The method according to any one of claims 15, 16, wherein the animal is a pet. 18. The method of claim 17 wherein the pet is a dog. 19. The method of any one of claims 15-18, wherein the injectable isoxazoline pharmaceutical composition is administered with a separate injectable parasiticide composition. 20. The method of claim 19, wherein the administration is simultaneous or sequential. 21. An injectable pharmaceutical composition according to any one of claims 1 to 13, wherein the D50 particle size distribution is from about 75 microns to about 130 microns and the D10 particle size is from about 30 microns to about 50 microns. 22. A kit for treating or preventing infestation of an animal, wherein the kit contains two or more containers a) a solid crystalline isoxazoline compound; b) a carrier medium containing a pharmaceutically acceptable excipient capable of forming a suspension with compound a); And c) instructions for combining the solid crystalline isoxazoline compound with the vehicle prior to injection, where for solid crystalline isoxazoline compound D50 volume-weighted particle size is from about 75 microns to about 130 microns and D10 particle size is from about 30 microns to about 50 microns. 23. The kit of claim 22 wherein the isoxazoline compound is fluralaner. 24. A method of treating or preventing infestation of an animal with parasites, comprising administering to an animal in need of this kit according to claims 22 or 23.