Antiparasitic isoxazoline compounds, long-acting injectable formulations comprising them, methods and uses thereof

Patent metadata

Field	Value
Publication number	US-11497732-B2
Application number	US-201916534912-A
Country	US
Kind code	B2
Filing date	Aug 7, 2019
Priority date	Feb 24, 2016
Publication date	Nov 15, 2022
Grant date	Nov 15, 2022

Abstract

This invention relates to long-acting injectable compositions for combating parasites in animals, comprising at least one isoxazoline active agent, a liquid PEG and/or a neutral oil, optionally a co-solvent, and optionally a pharmaceutically acceptable additive or excipient. This invention also provides new isoxazoline active agents with long-lasting efficacy against ectoparasites. The invention also provides for improved methods for eradicating, controlling, and preventing parasite infections and infestations in an animal comprising administering the novel isoxazoline compounds and long-acting injectable compositions of the invention to the animal in need thereof.

First claim

What is claimed is:

1. A long-acting injectable composition for the treatment of an ectoparasitic infection or infestation in an animal, said composition comprising
a) an effective amount of a parasiticidal isoxazoline active agent, which is a compound of formula (Ie):

or a pharmaceutically acceptable salt thereof;
b) a pharmaceutically acceptable polymer which is a liquid PEG and,
c) optionally, a co-solvent wherein said co-solvent is a polar solvent miscible in water, wherein no other pharmaceutically acceptable polymers are present, and wherein the composition treats the ectoparasitic infection or infestation for about 3 to 6 months.

2. The long-acting injectable composition according to claim 1 , wherein the parasiticidal isoxazoline active agent is enriched in an enantiomer.

3. The long-acting injectable composition according to claim 2 , wherein the enantiomer is a compound of formula (S)-Ie:

or a pharmaceutically acceptable salt thereof.

4. The long-acting injectable composition according to any one of claims 1 and 2 - 3 , wherein the liquid PEG is PEG 200, PEG 300 or PEG 400, or a mixture thereof.

5. The long-acting injectable composition according to any one of claims 1 and 2 - 3 , wherein the composition further comprises a co-solvent, and wherein the co-solvent is ethanol or isopropanol, or a mixture thereof.

6. The long-acting injectable composition according to claim 1 , wherein the composition further comprises a pharmaceutically acceptable excipient, and wherein the excipient is a surfactant.

7. The long-acting injectable composition according to claim 6 , wherein the surfactant is selected from the group consisting of glyceryl monooleate, sorbitan monooleate, sodium lauryl sulfate, poloxamers, propylene glycol monolaurate, glycerol caprylate/caprate, and a combination thereof.

8. The long-acting injectable composition according to claim 1 , wherein the composition comprises:
a) about 5 to 15% (w/v) of the parasiticidal isoxazoline compound of formula (Ie):

or a pharmaceutically acceptable salt thereof;
b) a pharmaceutically acceptable polymer which is a liquid PEG;
c) optionally, about 5% to 40% (w/v) of co-solvent, wherein said co-solvent is selected
from ethanol and isopropanol;
d) optionally, about 0.01% to about 2.0% (w/v) of an antioxidant; and
e) optionally, about 0.01% to about 5.0% (w/v) of a pharmaceutically acceptable additive, excipient or mixtures thereof

wherein the only pharmaceutically acceptable polymer present in said long-acting injectable composition is a liquid PEG and wherein the liquid PEG is present in the overall composition in a proportion representing the complement to 100% of the composition.

9. The long-acting injectable composition according to any one of claims 1 , 2 - 3 , and 8 , wherein said composition provides an efficacy of at least 90% against ticks for about 3 to 4 months.

10. The long-acting composition according to any one of claims 1 , 2 , 3 , and 8 , which further comprises an effective amount of at least one additional active agent.

11. The long-acting composition according to claim 10 , wherein the at least one additional pharmaceutically active agent is a macrocyclic lactone, a neonicotinoid active agent, a 1-N-arylpyrazole active agent, a cyclic depsipeptide, a benzimidazole, an imidazothiazole, a tetrahydropyrimidine active agent, an organophosphate active agent, levamisole, a paraherquamide active agent, a marcfortine active agent, praziquantel, closantel, pyrantel, morantel, clorsulon, a spinosyn active agent, a spinosoid active agent, an amino acetonitrile active agent, an aryloazol-2-yl cyanoethyl active agent or an insect growth regulator.

12. The long-acting composition according to claim 11 , wherein the macrocyclic lactone is abamectin, dimadectin, doramectin, emamectin, eprinomectin, ivermectin, latidectin, lepimectin, selamectin, ML-1,694,554, milbemectin, milbemycin D, moxidectin or nemadectin.

13. A method for treating ectoparasites in an animal in need thereof for a period of 3 to 6 months which comprises administering the long-acting injectable composition according to any one of claims 1 and 8 to said animal.

14. The method according to claim 13 wherein the animal is a dog, a cat, an ovine or a bovine.

15. The method according to claim 13 wherein the parasites are treated for about 5 to 6 months.

16. The method according to claim 13 wherein the ectoparasites are fleas and/or ticks.

17. The composition according to claim 1 , wherein the about 3 to 6 month treatment period is associated with a dose of the composition that is about 0.5 mg to about 2.5 mg of the isoxazoline active agent per kg of body weight of said animal.

18. The composition according to claim 3 , wherein the about 3 to 6 month treatment period is associated with a dose of the composition that is about 0.5 mg to about 2.5 mg of the isoxazoline active agent per kg of body weight of said animal.

19. The composition according to claim 8 , wherein the about 3 to 6 month treatment period is associated with a dose of the composition that is about 0.5 mg to about 2.5 mg of the isoxazoline active agent per kg of body weight of said animal.

Assignees

• Boehringer Ingelheim Animal Health Usa Inc

Inventors

• Le Hir De Fallois Loic Patrick
• Meng Charles Q
• Cady Susan Mancini
• Cheifetz Peter
• Galeska Izabela

Classifications

• A61K47/14

  Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters · CPC title

• A61K31/42 Primary

  Oxazoles · CPC title

• A61K47/10

  Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers · CPC title

• A61K31/69

  Boron compounds · CPC title

• C07F5/025

  Boronic and borinic acid compounds · CPC title