Non-animal product containing veterinary formulations

• US 20040037869A1
• Filed: 08/16/2002
• Published: 02/26/2004
• Est. Priority Date: 08/16/2002
• Status: Abandoned Application

• Current Assignee: Merial Limited (C.H. Boehringer Sohn AG & Co. KG)
• Original Assignee: Merial Limited (C.H. Boehringer Sohn AG & Co. KG)
• Inventors: Chen, Jun, Cleverly, Douglas, Azad, Abul, Muhitch, James, Hagenbuch, Michelle
• Application Number:
  US10/222,559
• Publication Number:
  US 20040037869A1
• Time in Patent Office: Days
• US Class Current: 424/442
• CPC Class Codes: A61K 9/0056 Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
• CPC Class Codes: A61K 9/2013 Organic compounds, e.g. phospholipids, fats
• CPC Class Codes: A61K 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/2059 Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 33/00 Antiparasitic agents

Abstract

This invention provides for a chewable veterinary formulation, which does not contain animal products, which comprises:

effective amount of at least one pharmaceutical agent;

at least one binder;

at least one disintegrant;

at least one non-animal product containing flavor or flavor derived from a non-animal source;

at least one binder;

at least one humectant;

at least one granulating solvent; and

optionally, at least one antioxidant, at least one buffering agent, at least one preservative, or at least one colorant.

This invention further provides for a process of producing chewable veterinary formulations as well as to a method for enhancing the patentability of oral veterinary formulations to an animal by adding a smoke hickory flavor to said formulation. This invention further provides for a tablet, which does not contain animal products.

Claims

1. A chewable veterinary formulation, which does not contain animal products, which comprises:

effective amount of at least one pharmaceutical agent;

at least one filler;

at least one disintegrant;

at least one non-animal product containing flavor or flavor derived from a non-animal source;

at least one binder;

at least one humectant;

at least one granulating solvent; and

optionally, at least one antioxidant, at least one pH modifier, at least one surfactant, at least one preservative, at least one lubricant or at least one colorant.

2. The chewable veterinary formulation according to claim 1, wherein,

the filler is selected from the group consisting of soy protein, corn cob, and corn glutton meal;

the disintegrant is selected from the group consisting of sodium starch glycolate, crospovidone, croscarmellose sodium, starch, micocrystalline cellulose, alginic acid, veegum, crospovidone, bentonite, and pregelatinized starch;

the binder is selected from the group consisting of polyvinyl pyrrolidone, povidone, starch, pregelatinized starch, gelatin, methylcellulose, hydroxypropyl cellulose, carboxymethyl cellulose sodium, ethylcellulose, sodium alginate, tragacanth, and acacia;

the humectant is selected from the group consisting of propylene glycol, glycerin, and polyethylene glycol 400; and

the granulating solvent is water or an aqueous sorbitol solution.

3. The chewable veterinary formulation according to claim 2, which further comprises an antioxidant and the antioxidant is an alpha tocopheral, ascorbic acid, ascrobyl palmitate, sodium ascorbate, sodium metabisulfate, n-propyl gallate, butylated hydroxy anisole, butylated hydoxy toluene, monothioglycerol or a mixture of any of the foregoing.

4. The chewable veterinary formulation according to claim 3, which further comprises a colorant and the colorant is a dye, an aluminum lake, caramel, colorant based upon iron oxide or a mixture of any of the foregoing.

5. The chewable veterinary formulation according to claim 4, which further comprises a preservative and the preservative is a compound selected from the group consisting of benzalkonium chloride, benzethonium chloride, benzoic acid, benzyl alcohol, bronopol, butylparaben, centrimide, chlorhexidine, chlorobutanol, chlorocresol, cresol, ethylparaben, imidurea, methylparaben, propylparaben, phenol, phenoxyethanol, phenylethyl, alcohol, phenylmercuric acetate, pheylmecuric borate, phenylmercuric nitrate, potassium sorbate, sodium benzoate, sodium propionate, sorbic acid, thimerosal, propyl paraben, myristyl gamma-picolinium chloride, paraben methyl, paraben propyl, quaternary ammonium compounds and a mixture of any of the foregoing.

6. The chewable veterinary formulation according to claim 1, wherein the pharmaceutical agent is a compound selected from the group consisting of antiparasitic agent, nordulisporic acid and its derivatives, estrogens, progestins, androgens, substituted pyridyl methyl derivatives, phenylpyrazols, COX-2 inhibitors, and proton pump inhibitors.

7. The chewable veterinary formulation according to claim 5, wherein the pharmaceutical agent is selected from the group consisting of avermectins, milbemycins, nordulisporic acid and its derivatives, estrogens, progestins, androgens, substituted pyridyl methyl derivatives, phenylpyrazols, COX-2 inhibitors, 2-acyl-4-oxopyrazino-isoquinoline derivatives, 1,4,5,6-tetrahydro-2-[(2-substituted)vinyl pyrimidine derivatives, 2-[(2-substituted)vinyl]-2-imidazoline derivatives and proton pump inhibitors.

8. The chewable veterinary formulation according to claim 7, which further comprises a surfactant selected from the group consisting of glyceryl monooleate, polyoxyethylene, sorbitan esters, polyvinyl alcohol, sodium lauryl sulfate and poloxomers.

9. The chewable veterinary formulation according to claim 7, which further comprises a lubricant and the lubricant is selected from the group consisting of corn oil, polyethylene glycol, mineral oil, hydrogenated vegetable oil, peanut oil or castor oil.

10. The chewable veterinary formulation, according to claim 1 which comprises:

an effective amount of a pharmaceutical agent selected from the group consisting of avermectins, milbemycins, nordulisporic acid and its derivatives, estrogens, progestins, androgens, substituted pyridyl methyl derivatives, phenylpyrazols, COX-2 inhibitors, 2-acyl-4-oxopyrazino-isoquinoline derivatives, 1,4,5,6-tetrahydro-2-[(2-substituted)vinyl pyrimidine derivatives, 2-[(2-substituted)vinyl]-2-imidazoline derivatives and proton pump inhibitors;

about 20 to about 60% of a filler selected from the group consisting of soy protein, corn cob, or corn glutton meal;

about 1 to about 20% of a disintegrant;

about 0.1 to about 20% of a non-animal product containing flavor or a flavor derived from a non-animal source;

about 0.5 to 10% a binder;

about 5 to about 20% of a humectant; and

about 5 to about 20% granulating solvent,

based upon total weight of formulation.

11. The chewable veterinary formulation according to claim 10, which further comprises 0.05% to about 1.0% of an antioxidant, about 0.05 to about 1.0% of a preservative, about 0.01 to 20% of a lubricant and about 0.01 to about 10% of a colorant.

12. The chewable veterinary formulation according to claim 1, wherein the pharmaceutical agent is a compound selected from the group consisting of fipronil, imidacloprid, ivermectin, praziquantel, abamectin, ememectin, epinomectin, doramectin, moxidectin, selemectin, 3-(cyclopropylmethoxy)-5,5-dimethyl-4-(4-methylsulfonyl)phenyl)-5H-furan-2-one, 3-(cyclopropylethoxy)5,5-dimethyl-4-(4-methylsulfonyl)phenyl)-5H-furan-2-one, and omeprazole or, if available, a pharmaceutically acceptable salts or hydrates of said compounds.

13. The chewable veterinary formulation as claimed in claim 1 which comprises two pharmaceutical agents.

40. A process for preparing a chewable veterinary formulation according to claim 1, which comprises the step of:

(a) blending the pharmaceutical agent, binder, disintegrant, and non-animal containing flavor or a flavor derived from a non-animal source;

(b) adding the water and the humectant to the mixture from step (a) and mixing the mixture; and

(c) without drying, extruding the mixture.

14. The chewable veterinary formulation wherein one of the pharmaceutical agents is an avermectin or a milbenycin and the second pharmaceutical agent is a 2-acyl-4-oxo-pyrazino-isoquinoline derivative or pyrantel.

15. The chewable veterinary formulation according to claim 14, wherein the avermectin or milbemycin is eprinomectin and the second pharmaceutical agent is praziquantel.

16. A chewable veterinary formulation, which does not contain animal products, which comprises:

effective amount of at least one pharmaceutical agent;

a filler selected from the group consisting of soy protein, corn cob, or corn glutton meal;

disintegrant;

a non-animal product containing flavor or a flavor derived from non-animal sources which is a hickory smoke flavor or a beef flavor;

a binder;

humectant;

granulating solvent; and

optionally, an antioxidant, a pH modifier, preservative, a surfactant, a lubricant or a colorant.

17. The chewable veterinary formulation, according to claim 16, which comprises:

an effective amount of at least one pharmaceutical agent;

about 20 to about 60% of a filler selected from the group consisting of soy protein, corn cob, or corn glutton meal;

about 1 to about 20% of a disintegrant;

about 0.1 to about 20% of a the hickory smoke flavor;

about 0.5 to about 10% a binder;

about 5 to about 20% of a humectant; and

about 5 to about 20% granulating solvent;

and, optionally

about 0.05% to about 1.0% of an antioxidant;

about 0.05 to about 1.0% of a preservative; and

a pH modifier;

about 0.001% to about 1% of a surfactant;

about 0.01% to about 20% of a lubricant

about 0.01 to about 10% of a colorant,

based upon total weight of formulation.

18. The chewable veterinary formulation, according to claim 17, wherein the pharmaceutical agent is an avermectin or a milbemycin.

19. The chewable veterinary formulation according to claim 18, wherein the avermectin or milbemycin is ivermectin, abamectin, ememectin, eprinomectin, doramectin, moxidectin, or selamectin.

20. The chewable veterinary formulation according to claim 16, which further comprises a second pharmaceutical agent.

21. The chewable veterinary formulation according to claim 20 wherein the avermectin or milbemycin is eprinomectin, the second pharmaceutical agent is praziquantel, the filler is soy protein, the disintegrant is crospovidone, the binder is povidone, the humectant is polyethylene glycol 400, the pH modifier is citric acid, the preservative is sodium propionate, the surfactant is a poloxomer, the lubricant is corn oil and the non-animal product containing flavor or flavor derived from non-animal source is a beef flavor.

22. The chewable veterinary formulation according to claim 17, wherein the pharmaceutical agent is a COX-2 inhibitor.

23. The chewable veterinary formulation according to claim 22, wherein the COX-2 inhibitor is 3-(cyclopropylmethoxy)-5,5-dimethyl-4-(4-methylsulfonyl)phenyl)-5H-furan-2-one or 3-(cyclopropylethoxy)-5,5-dimethyl-4-(4-methylsulfonyl)phenyl)-5H-furan-2-one or pharmaceutically acceptable salts or hydrates of these compounds.

24. The chewable veterinary formulation according to claim 23, wherein the COX-2 inhibitor is the polymorphic B form of 3-(cyclopropylmethoxy)-4-[4-(methylsulfonyl)phenyl-5,5-dimethyl]-5H-furan-2-one.

25. The chewable veterinary formulation according to claim 17, wherein the pharmaceutical agent is a substituted pyridylmethyl derivative or a phenylpyrazole.

26. The chewable veterinary formulation according to claim 25, wherein the pharmaceutical agent is imidacloprid or fipronil.

27. The chewable veterinary formulation according to claim 16, wherein the pharmaceutical agent is a NSAID.

28. The chewable veterinary formulation according to claim 27, wherein the pharmaceutical agent is carprofen, flunixin, ketoprofen, meloxicam, naproxen or phenylbutazone.

29. The chewable veterinary formulation according to claim 17, wherein the pharmaceutical agent is a proton pump inhibitor.

30. The chewable veterinary formulation according to claim 29, wherein the proton pump inhibitor is omeprazole or a salt thereof.

31. The chewable veterinary formulation according to claim 17, wherein the pharmaceutical agent is an estrogen, a progenstin, or an androgen.

32. The chewable veterinary formulation according to claim 17, wherein the pharmaceutical agent is an insect growth regulator.

33. The chewable veterinary formulation according to claim 17, wherein the disintegrant is selected from the group consisting of sodium starch glycolate, crospovidone, croscarmellose sodium, starches, microcrystalline cellulose, alginic acid, veegum, crospovidone, bentonite, and pregelatinized starch.

34. The chewable veterinary formulation according to claim 17, wherein the binder is selected from the group consisting of polyvinyl pyrrolidone, povidone, starch, pregelatinized starch, gelatin, methylcellulose, hydroxypropyl cellulose, carboxymethyl cellulose sodium, ethylcellulose, sodium alginate, tragacanth, and acacia.

35. The chewable veterinary formulation according to claim 17, wherein the humectant is selected from the group consisting of propylene glycol, glycerin, and polyethylene glycol 400.

36. The chewable veterinary formulation according to claim 17, wherein the granulating solvent is water or an aqueous sorbitol solution.

37. The chewable veterinary formulation according to claim 16, which comprises an antioxidant and the antioxidant is selected from the group consisting of alpha tocopherol, ascorbic acid, ascrobyl palmitate, sodium ascorbate, sodium metobisulfate, n-propyl gallate, butylated hydroxy anisole, butylated hydroxy toluene of a mixture of any of the foregoing and monothioglycerol.

38. The chewable veterinary formulation according to claim 16, which comprises a preservative and the preservative and the preservative is selected from the group consisting of the parabens, benzalkonium chloride, benzethonium chloride, benzoic acid, benzyl alcohol, bronopol, cetrimide, chlorhexidine, chlorobutanol, chlorocresol, cresol, imidurea, phenol, phenoxyethanol, phenylethyl alcohol, phenylmercuric acetate, phenylmercuric borate, phenylmercuric nitrate, potassium sorbate, sodium benzoate, sodium propionate, sorbic acid, and thimerosal, propyl paraben, myristyl gamma-picolinium chloride, paraben methyl, paraben propyl, quaternary ammonium compounds, and a mixture of any of the foregoing.

39. The chewable veterinary formulation according to claim 38, comprises a pH modifier and a lubricant and the pH modifier is selected from the group consisting of citric acid, fumeric acid and malic acid and a lubricant which is selected from the group consisting of polyethylene glycols, corn oil, mineral oil, hydrogenated vegetable oils, peanut oil and castor oil.

41. An oral veterinary formulation, which does not contain animal products, that comprises an effective amount of at least one pharmaceutical active agent and a non-animal product containing or flavor derived from non-animal sources which is a hickory smoke flavor.

42. The oral veterinary formulation according to claim 41, wherein the pharmaceutical agent is a compound selected from the group consisting of avermectins, milbemycins, nordulisporic acid and its derivatives, estrogens, progestins, androgens, substituted pyridyl methyl derivatives, phenylpyrazols, COX-2 inhibitors, 2-acyl-4-oxo-pyrazino-isoquinoline derivative, pyrantel and proton pump inhibitors.

43. The oral veterinary formulation according to claim 41, wherein the pharmaceutical agent is fipronil or a COX-2 inhibitor.

44. The oral veterinary formulation according to claim 41, which comprises two active pharmaceutical agents which are eprinomectin and praziquantel.

45. The oral veterinary formulation according to claim 41, wherein the COX-2 inhibitor is 3-(cyclopropylmethoxy)-5,5-dimethyl-4-(4-methylsulfonyl)phenyl)-5H-furan-2-one or 3-(cyclopropylethoxy)5,5-dimethyl-4-(4-methylsulfonyl)phenyl)-5H-furan-2-one.

46. The oral veterinary formulation according to claim 41, which is in the form of a tablet.

47. The oral veterinary formulation according to claim 41, which is in the form of a liquid.

48. A method for enhancing the palatability an oral veterinary formulation, which does not contain animal products, to an animal which comprises adding a hickory smoke flavor, which is a non-animal product containing or a flavor derived from a non-animal source, to the oral veterinary formulation.

49. The method according to claim 48, wherein the hickory smoke flavor is absorbed on the surface of dextrose.

50. The method according to claim 48, wherein the hickory smoke flavor is absorbed on the surface of yeast.

51. The method according to claim 48, wherein the hickory barbecue flavor further comprises carmel.

52. A tablet, which does not contain animal products, which comprises

an effective amount of at least one pharmaceutical agent;

at least one filler;

at least one non-animal product containing flavor or flavor derived from a non-animal source;

at least one lubricant;

at least one flow aid; and

optionally, at least one antioxidant, at least one pH modifier, at least one binder, at least one disintegrant, at least one surfactant, at least one preservative, and at least one colorant, and

is optionally coated with at least one coating.

53. The tablet according to claim 52, wherein

the filer is selected from the group consisting of anhydrous lactose, hydrated lactose, spray-dried lactose, crystalline maltose, and a maltodextin;

the flow aid is selected from the group consisting of silicone dioxide, silica gel, talc, starch, calcium stearate, magnesium stearate, and aluminum magnesium stearate; and

the lubricant is selected from the group consisting of magnesium stearate, calcium stearate, stearic acid and waxes.

54. The tablet according to claim 53, wherein

the disintegrant is selected from the group consisting of sodium starch glycolate, crospovidone, croscarmellose sodium, starch, micocrystalline cellulose, alginic acid, veegum, crospovidone, bentonite, and pregelatinized starch;

and

the binder is selected from the group consisting of polyvinyl pyrrolidone, povidone, starch, pregelatinized starch, gelatin, methylcellulose, hydroxypropyl cellulose, carboxymethyl cellulose sodium, ethylcellulose, sodium alginate, tragacanth, and acacia.

55. The tablet according to claim 54, which further comprises a colorant and the colorant is a dye, an aluminum lake, caramel, colorant based upon iron oxide or a mixture of any of the foregoing.

56. The tablet according to claim 55, wherein the oxide is yellow iron oxide or red iron oxide.

57. The tablet according to claim 52, wherein pharmaceutical agent is a compound selected from the group consisting of an antiparasitic agent, nordulisporic acid and its derivatives, estrogens, progestins, androgens, substituted pyridyl methyl derivatives, phenylpyrazols, COX-2 inhibitors, and proton pump inhibitors.

58. The tablet according to claim 54, wherein the pharmaceutical agent is pharmaceutical therapeutic agent is selected from the group consisting of avermectins, milbemycins, nordulisporic acid and its derivatives, estrogens, progestins, androgens, substituted pyridyl methyl derivatives, phenylpyrazols, COX-2 inhibitors, 2-acyl-4-oxopyrazino-isoquinoline derivatives, 1,4,5,6-tetrahydro-2-[(2-substituted)vinyl pyrimidine derivatives, 2-[(2-substituted)vinyl]-2-imidazoline derivatives and proton pump inhibitors.

59. The tablet according to claim 55, wherein the pharmaceutical agent is a COX-2 inhibitor.

60. The tablet according to claim 59, which comprises microcrystalline cellulose, caramel, yellow iron oxide, hydroxypropyl cellulose, croscasmellose sodium, collodial silicone dioxide, magnesium stearate, and lactose monohydrate.

61. The tablet according to claim 60, wherein the COX-2 inhibitors is 3-(cyclopropylmethoxy)-5,5-dimethyl-4-(4-methylsulfonyl)phenyl)-5H-furan-2-one, 3-(cyclopropylethoxy)-5,5-dimethyl-4-(4-methylsulfonyl)phenyl)-5H-furan-2-one.

62. The tablet according to claim 58, wherein pharmaceutical agent is a melbemycin or avermectin and is selected from the group consisting of is ivermectin, abamectin, ememectin, eprinomectin, doramectin, moxidectin, and selamectin.

63. The tablet according to claim 58, which comprises two pharmaceutical agents.

64. The tablet according to claim 63, wherein one pharmaceutical agent is an avermectin or a milbemycin and the second is praziquantel or pyrantel.

65. The tablet according to claim 64, wherein avermectin or milbemycin is the aprinomectin.

66. The tablet according to claim 54, is coated.

67. The tablet according to claim 66, wherein the coating is a sugar coating or a film coating.