Patent EA-002497-B1 (EA)
Title: Long acting injectable formulations containing hydrogenated castor oil
Inventor: WILLIAMS JAMES B
IPC: A61K31/27
Filed: 1998-09-14
Abstract: 1. A long-acting injectable formulation comprising: (a) a therapeutic agent selected from the group consisting of insecticides, acaricides, parasiticides, growth enhancers and oil-soluble NASIDS, (b) hydrogenated castor oil, and (c) a hydrophobic carrier comprising: (i) triacetin, benzylbenzoate or ethyloleate or a combination thereof; and (ii) acylated monoglycerides, propyldicaprylates/dicaprates, caprylic/capric acid triglycerides, or a combination thereof. 2. A long-acting injectable formulation comprising: (a) a therapeutic agent selected from the group consisting of avermectins, milbemycins, nodulisporic acid and its derivatives, estrogens, progestins, androgens, substituted pyridylmethyl derivatives, phenylpyrazoles, and COX-2 inhibitors, (b) hydrogenated castor oil, and (c) a hydrophobic carrier comprising: (i) triacetin, benzylbenzoate or ethyloleate or a combination thereof; and (ii) acetylated monoglycerides, propyldicaprylates/dicaprates, caprylic/capric triglycerides, or a combination thereof. 3. The long-acting injectable formulation according to Claim 1 comprising (a) about 1.0 to about 10.0 % w/v of a therapeutic agent; (b) about 0.3 to about 5% w/v of hydrogenated castor oil; (c) a hydrophobic carrier comprising: (i) about 30 to about 45% v/v of triacetin; benzylbenzoate or ethyloleate; and (ii) about 55 to 70% of v/v of acetylated monoglycerides, propyl dicaprylates/dicaprates, or caprylic/capric triglycerides. 4. The long-acting injectable formulation according to Claim 2 comprising: (a) about 1.0 to about 10.0% w/v of a therapeutic agent; (b) about 0.3 to about 5% w/v of hydrogenated castor oil; (c) a hydrophobic carrier comprising: (i) about 30 to about 45% v/v of triacetin; benzylbenzoate or ethyloleate; and (ii) about 55 to 70% of v/v of acetylated monoglycerides, propyldicaprylates/dicaprates, or caprylic/capric triglycerides. 5. The long-acting injectable formulation according to Claim 2 wherein about 2.5 to about 5.0% w/v of a therapeutic agent is present. 6. The long-acting injectable formulation according to Claim 2 wherein the therapeutic agent is an avermectin or a milbemycin. 7. The long-acting injectable formulation according to Claim 6, wherein the avermectin is ivermectin, abamectin, ememectin, eprinomectin, or doramectin and the milbemycin is moxidectin. 8. The long-acting injectable formulation according to Claim 2, wherein the therapeutic agent is an estrogen, progestin or androgen. 9. The long-acting injectable formulation according to Claim 8, where the estrogen, progestin or androgen is estradiolbenzoate, progesterone, or trenbolone acetate. 10. The long-acting injectable formulation according to Claim 2, wherein the therapeutic agent is nodulisporic acid or its derivatives. 11. The long-acting injectable formulation according to Claim 2, wherein the therapeutic agent is a substituted pyridylmethyl derivative or a phenylpyrazole. 12. The long-acting injectable formulation according to Claim 11, wherein the therapeutic agent is imidacloprid or fipronil. 13. The long-acting injectable formulation according to Claim 2, wherein the therapeutic agent is a COX-2 inhibitor. 14. The long-acting injectable formulation according to Claim 1, wherein the therapeutic agent is an oil-soluble, nonsteroidal anti-inflammatory drug. 15. The long-acting injectable formulation according to Claim 14, wherein the therapeutic agent is carprofen, flunixin, ketoprofen, meloxicam, naproxen or phenylbutazone. 16. The long-acting injectable formulation according to Claim 1, wherein the therapeutic agent is an insect growth regulator. 17. The long-acting injectable formulation according to Claim 16, wherein the therapeutic agent is difluo-benzuron, lufenuron, methoprene, phenoxycarb, pyriproxyfen, and cy-romazine. 18. The long-acting injectable formulation according to Claim 1, which further comprises an antioxidant or a preservative. 19. The long-acting injectable formulation according to Claim 2 where about 1 to about 3.0 % w/v of hydrogenated caster oil is present and hydrophobic carrier comprises about 40% v/v of triacetin, benzlybenzoate or ethyloleate and about 60% v/v of acetylated monoglycerides, propyl dicaprylates/dicaprates, or caprylic/capric triglycerides. 20. The long-acting injectable formulation of Claim 2, which comprises: (a) about 1.0 to about 5.0% w/v of an avermectin compound, (b) about 1 to about 3% w/v of hydrogenated castor oil, and (c) about 30 to about 45% v/v of triacetin and 55 to 70% v/v of acetylated monoglycerides. 21. The long-acting injectable formulation of Claim 2, which comprises: (a) about 3.15% w/v of ivermectin, (b) about 1% w/v of hydrogenated castor oil, and (c) about 40% of triacetin and up to about 60% v/v of acetylated monoglycerides. 22. The long-acting injectable formulation of Claim 2, which further comprises an antioxidant. 23. The long acting injectable formulation of Claim 2, which further comprises a preservative. 24. The long acting injectable formulation of Claim 22 wherein said antioxidant is selected from n-propylgallate, BHA, BHT and monothioglycerol. 25. The long-acting injectable formulation of Claim 23 wherein said preservative is selected from the parabens. 26. The long-acting injectable formulation of Claim 21, which further comprises an antioxidant selected from n-propylgallate, BHA, BHT and monothioglycerol. 27. The long-acting injectable formulation of Claim 26 which further comprises a preservatives selected from the parabens. 28. The long acting injectable formulation of Claim 21 which further comprises BHT and one or more preservatives from the parabens. 29. A method for the prevention or treatment of parasitic infestation in a host in need thereof, which comprises parentally administering a single dose of a long-acting injectable formulation of Claim 6 to said host. 30. A method for the prevention or treatment of parasitic infestation in a host in need thereof for a minimum of 42 days, which comprises administering to said host a single dose of a long-acting injectable formulation of Claim 1. 31. A method for the prevention or treatment of parasitic infestation in cattle for a minimum of 42 days, which comprises administering to said cattle a single dose of a long-acting injectable formulation of Claim 2. 32. A method for the prevention or treatment of parasitic infestation in cattle for a minimum of 42 days, which comprises administering to said cattle a single dose of a long-acting injectable formulation of Claim 21. 33. A method for treating or preventing insect infestation for an extended period of time in a host in need thereof, which comprises parentally administering a single-dose of a long-acting injectable formulation according to Claim 10 to said host. 34. The method according to Claim 33, wherein the insects are fleas. 35. A method for treating or preventing insect infestation for an extended period of time in a host in need thereof, which comprises parenterally administering a single-dose of a long-acting injectable formulation according to Claim 11 to said host. 36. The method according to Claim 35 wherein the injectable formulation as the therapeutic agent is imidacloprid or fipronil and the insects are fleas. 37. A method for promoting growth in animals, which comprises administering a single does of a long-acting injectable formulation according to Claim 8 to said animal. 38. A method for treating inflammation, pain, or fever for an extended period of time in a host in need thereof which comprises administering a single-dose of a long-acting injectable formulation according to Claim 14 to a host in need thereof.