Chlortetracycline-containing animal feed compositions and methods for their use

• US 6,506,402 B1
• Filed: 06/05/2000
• Issued: 01/14/2003
• Est. Priority Date: 10/05/1998
• Status: Expired due to Term

• Current Assignee: Pennfield Oil Company
• Original Assignee: Pennfield Oil Company
• Inventors: Winstrom, Willis L.
• Primary Examiner(s): Dees, José G.
• Assistant Examiner(s): DeWitty, Robert M.
• Application Number:
  US09/587,411
• Time in Patent Office: 953 Days
• Field of Search: 426/633, 426/53, 426/54, 424/80, 435/48
• US Class Current: 424/442
• CPC Class Codes: A23K 20/195 Antibiotics
• CPC Class Codes: C12P 29/00 Preparation of compounds containing a naphthacene ring system, e.g. tetracycline C12P19/00 takes precedence

Abstract

The present invention provides improved chlortetracycline-containing animal feed compositions and processes and apparatuses for their preparation. In certain embodiments, raw fermentation broth comprising chlortetracycline is divided into two portions. The first portion is mixed with a compound that complexes chlortetracycline. The second portion is acidified and the solids are removed. The acidified liquid is treated with a complexing agent to produced a chlortetracycline complex. The first and second portions thus treated are then mixed and the mixture is passed on to a filter press or other means for separation of the solids to produce a wet cake comprising complexed chlortetracycline. In alternative embodiments, the second portion may be acidified and filtered and admixed with the first portion prior to the complexing step. The resulting mixture is passed on to a filter press or other means for separation of the solids. In still further embodiments, the complexing steps are replaced with neutralizing or basification steps to yield the free base form of chlortetracycline. The wet filter cake comprising chlortetracycline and fermentation solids is dried and sized to produce a dried semi-finished product in the form of a powder, meal, granules, pellets, tablets, etc. The semi-finished product may be standardized to produce an animal feed supplement having a desired potency. In a further aspect, the present invention relates to a method of combating microbial infection and promoting growth in animals comprising orally administering to said animals an effective amount of an animal composition according to the present invention.

Claims

1. An animal feed composition comprising complexed chlortetracycline in a solid carrier, said solid carrier comprising fermentation solids derived from a fermentation broth produced by fermentation of an organism producing chlortetracycline, wherein said animal feed composition is prepared by:

(a) providing first and second quantities of fermentation broth comprising chlotetracycline, said first and second quantities of fermentation broth produced by fermentation of an organism producing chlortetracycline, said first and second quantities of fermentation broth comprising fermentation solids and liquids;

(b) adjusting the pH of the first quantity of fermentation broth to a value of about 7 or greater to produce fermentation broth containing chlortetracycline;

(c) lowering the pH of said second quantity of fermentation broth to a level sufficient to dissolve the chlortetracycline in said second quantity of fermentation broth;

(d) removing solids from said pH-adjusted second quantity of fermentation broth and collecting liquid containing dissolved chlortetracycline;

(e) adjusting the pH of said liquid containing dissolved chlortetracycline to a value of about 7 or greater to produce a suspension;

(f) mixing said fermentation broth containing complexed chlortetracycline from step (b) and said suspension from step (e);

(g) removing liquids from the mixture to produce a chlortetracycline containing fermentation product having a low moisture content; and

(h) sizing said low moisture content fermentation product to produce a particulate chlortetracycline-containing fermentation product having a predetermined particle size or range of particle sizes.

2. A composition according to claim 1, wherein adjusting the pH of the first quantity of fermentation broth to a value of about 7 or greater to produce fermentation broth containing chlortetracycline includes adding a chlortetracycline complexing compound in an amount sufficient to produce fermentation broth containing complexed chlortetracycline.

3. A composition according to claim 1, wherein adjusting the pH of the first quantity of fermentation broth to a value of about 7 or greater to produce fermentation broth containing chlortetracycline produces a fermentation broth containing chlortetracycline in free base form.

4. A composition according to claim 1, wherein adjusting the pH of said liquid containing dissolved chlortetracycline to a value of about 7 or greater to produce a suspension includes adding a chlortetracycline complexing compound in an amount sufficient to produce a suspension of complexed chlortetracycline.

5. A composition according to claim 1, wherein adjusting the pH of said liquid containing dissolved chlortetracycline to a value of about 7 or greater to produce a suspension produces a suspension of chlortetracycline in free base form.

6. A composition according to claim 1, wherein the ratio of said first quantity of fermentation broth to said second quantity of fermentation broth is from about 1:

10 to about 10;

1.

7. A composition according to claim 1, wherein the ratio of said first quantity of fermentation broth to said second quantity of fermentation broth is from about 1:

5 to about 5;

1.

8. A composition according to claim 1, wherein the ratio of said first quantity of fermentation broth to said second quantity of fermentation broth is from about 1:

3 to about 3;

1.

9. A composition according to claim 1, wherein the first quantity of fermentation broth and the second quantity of fermentation broth are from the same fermentation batch.

10. A composition according to claim 1, wherein the first quantity of fermentation broth and the second quantity of fermentation broth are from different fermentation batches.

11. A composition according to claim 2, wherein the chlortetracycline complexing compound added to said first quantity of fermentation broth is calcium carbonate.

12. A composition according to claim 1, wherein the pH of the first quantity of fermentation broth is adjusted by the addition of aqueous ammonia.

13. A composition according to claim 1, wherein the pH of the first quantity of fermentation broth is adjusted to a value of from about 7.5 to about 8.0.

14. A composition according to claim 1, wherein the pH of the second quantity of fermentation broth is adjusted by adding a mineral acid.

15. A composition according to claim 1, wherein the pH of the second quantity of fermentation broth is adjusted by adding one or more acids selected from the group consisting of oxalic acid, hydrochloric acid, and sulfuric acid.

16. A composition according to claim 1, wherein the pH of the second is quantity of fermentation broth is adjusted to a value of about 4.0 or less.

17. A composition according to claim 1, wherein the pH of the second quantity of fermentation broth is adjusted to a value of about 2.0 or less.

18. A composition according to claim 1, wherein the pH of the second quantity of fermentation broth is adjusted to a value of about 1.0 to about 1.3.

19. A composition according to claim 2, wherein said chlortetracycline complexing compound added to said liquid containing dissolved chlortetracycline is calcium carbonate and the pH of said liquid containing dissolved chlortetracycline is adjusted by the addition of aqueous ammonia.

20. A composition according to claim 5, wherein the pH of said liquid containing dissolved chlortetracycline is adjusted by the addition of aqueous ammonia.

21. A composition according to claim 1, wherein the pH of said liquid containing dissolved chlortetracycline is adjusted to a pH of from about 7.5 to about 8.0.

22. A composition according to claim 1, wherein the removal of liquids in step g) utilizes one or more of the following:

a filter press, centrifugal filter, rotary vacuum filter, oven, tray dryer, tunnel dryer, spray dryer, spray granulator, fluid bed dryer, shelf dryer, drum dryer, rotary dryer, microwave dryer, and contact dryer.

23. A composition according to claim 1, wherein the removal of liquids in step (g) utilizes at least one of:

a filter press, a centrifuge, and an oven.

24. A composition according to claim 1, wherein said filter cake is dried to a moisture content of from about 2% to about 12%.

25. A composition according to claim 1, wherein said filter cake is dried to a moisture content of from about 2% to about 6%.

26. A composition according to claim 1, wherein said low moisture content fermentation product comprises chlortetracycline in an amount from about 30% to about 75%.

27. A composition according to claim 1, wherein said solid having low moisture content comprises chlortetracycline in an amount from about 35% to about 65%.

28. A composition according to claim 1, wherein said solid having low moisture content comprises chlortetracycline in an amount from about 44% to about 55%.

29. A composition according to claim 1, wherein said particles are in the form of a powder, meal, pellets, granules, or tablets.

30. A composition according to claim 1, wherein said particles have a diameter of from about 150 μ

m to about 2 mm.

31. A composition according to claim 1, wherein said particles are produce without any compression or compaction step.

32. A composition according to claim 1, wherein said particles are produced with a compression or compaction step.

33. A composition according to claim 1, further comprising the step of blending said particulate chlortetracycline-containing fermentation product with at least one diluent selected from the group consisting of an edible feed material, a mineral product, and an oil.

34. A composition according to claim 33, further comprising the step of admixing said granules with a nonmedicated animal feedstuff.

35. A composition according to claim 33, wherein said edible feed material is rice hulls.

36. A composition according to claim 33, wherein said mineral product is limestone.

37. A composition according to claim 33, wherein said oil is mineral oil.

55. A composition according to claim 33, wherein the removal of liquids in step (g) utilizes at least one of:

a filter press, a centrifuge, and an oven.

56. A composition according to claim 33, wherein said filter cake is dried to a moisture content of from about 2% to about 12%.

57. A composition according to claim 33, wherein said filter cake is dried to a moisture content of from about 2% to about 6%.

58. A composition according to claim 33, wherein said low moisture content fermentation product comprises chlortetracycline in an amount from about 30% to about 75%.

59. A composition according to claim 33, wherein said solid having low moisture content comprises chlortetracycline in an amount from about 35% to about 65%.

60. A composition according to claim 33, wherein said solid having low moisture content comprises chlortetracycline in an amount from about 189% to about 55%.

61. A composition according to claim 33, wherein said particles are in the form of a powder, meal, pellets, granules, or tablets.

62. A composition according to claim 33, wherein said particles have a diameter of from about 150 μ

m to about 2 mm.

63. A composition according to claim 33, wherein said particles are produced without any compression or compaction step.

64. A composition according to claim 33, wherein said particles are produced with a compression or compaction step.

65. A composition according to claim 33, further comprising the step of blending said particulate chlortetracycline-containing fermentation product with at least one diluent selected from the group consisting of an edible feed material, a mineral product, and an oil.

66. A composition according to claim 65, further comprising the step of admixing said granules with a nonmedicated animal feedstuff.

67. A composition according to claim 65, wherein said edible feed material is rice hulls.

68. A composition according to claim 65, wherein said mineral product is limestone.

69. A composition according to claim 65, wherein said oil is mineral oil.

102. A composition according to claim 1, wherein the fermentation product has a sufficient antibiotic activity to treat an animal.

38. An animal feed composition comprising complexed chlortetracycline in a solid carrier, said solid carrier comprising fermentation solids derived from a fermentation broth produced by fermentation of an organism producing chlortetracycline, wherein said animal feed composition is prepared by:

(a) providing first and second quantities of fermentation broth comprising chlortetracycline, said first and second quantities of fermentation broth produced by fermentation of an organism producing chlortetracycline, said first and second quantities of fermentation broth comprising fermentation solids and liquids;

(b) lowering the pH of said second quantity of fermentation broth to a level sufficient to dissolve the chlortetracycline in said second quantity of fermentation broth;

(c) removing solids from said pH-adjusted second quantity of fermentation broth and collecting liquid containing dissolved chlortetracycline;

(d) mixing said liquid containing dissolved chlortetracycline with said first quantity of fermentation broth to produce a mixture;

(e) adjusting the pH of the mixture of step (d) to a value of about 7 or greater;

(f) removing liquids from the mixture of step (e) to produce a complexed chlortetracycline-containing fermentation product having a low moisture content; and

(h) sizing said low moisture content fermentation product to produce a particulate chlortetracycline-containing fermentation product having a predetermined particle size or range of particle sizes.

39. A composition according to claim 38, wherein adjusting the pH of the mixture of step (d) to a value of about 7 or greater includes adding a chlortetracycline complexing compound in an amount sufficient to complex the chlortetracycline in the mixture.

40. A composition according to claim 38, wherein the pH of the mixture of step (d) is adjusted to a value of about 7 or greater to form a mixture containing chlortetracycline in the free base formula.

41. A composition according to claim 38, wherein the ratio of said first quantity of fermentation broth to said second quantity of fermentation broth is from about 1:

10 to about 10;

1.

42. A composition according to claim 38, wherein the ratio of said first quantity of fermentation broth to said second quantity of fermentation broth is from about 1:

5 to about 5;

1.

43. A composition according to claim 38, wherein the ratio of said first quantity of fermentation broth to said second quantity of fermentation broth is from about 1:

3 to about 3;

1.

44. A composition according to claim 38, wherein the first quantity of fermentation broth and the second quantity of fermentation broth are from the same fermentation batch.

45. A composition according to claim 38, wherein the first quantity of fermentation broth and the second quantity of fermentation broth are from different fermentation batches.

46. A composition according to claim 39, wherein the chlortetracycline complexing compound added to said first quantity of fermentation broth is calcium carbonate.

47. A composition according to claim 38, wherein the pH of the mixture is adjusted in step (e) by the addition of aqueous ammonia.

48. A composition according to claim 38, wherein the pH of the mixture is adjusted in step (e) to a value of from about 7.5 to about 8.0.

49. A composition according to claim 38, wherein the pH of the second quantity of fermentation broth is adjusted by adding a mineral acid.

50. A composition according to claim 38, wherein the pH of the second quantity of fermentation broth is adjusted by adding one or more acids selected from the group consisting of oxalic acid, hydrochloric acid, and sulfuric acid.

51. A composition according to claim 38, wherein the pH of the second quantity of fermentation broth is adjusted to a value of about 4.0 or less.

52. A composition according to claim 38, wherein the pH of the second quantity of fermentation broth is adjusted to a value of about 2.0 or less.

53. A composition according to claim 38, wherein the pH of the second quantity of fermentation broth is adjusted to a value of about 1.0 to about 1.3.

54. A composition according to claim 38, wherein the removal of liquids in step (g) utilizes one or more of the following:

a filter press, centrifugal filter, rotary vacuum filter, oven, tray dryer, tunnel dryer, spray dryer, spray granulator, fluid bed dryer, shelf dryer, drum dryer, rotary dryer, microwave dryer, and contact dryer.

103. A composition according to claim 38, wherein the fermentation product has a sufficient antibiotic activity to treat an animal.

70. An animal feed composition comprising complexed chlortetracycline in a solid carrier, said solid carrier comprising fermentation solids derived from a fermentation broth produced by fermentation of an organism producing chlortetracycline, wherein said animal feed composition is prepared by:

(a) providing first and second quantities of fermentation broth comprising chlortetracycline, said first and second quantities of fermentation broth produced by fermentation of an organism producing chlortetracycline, said first and second quantities of fermentation broth comprising fermentation solids and liquids;

(b) adjusting the pH of the first quantity of fermentation broth to a value of about 7 or greater and adding a chlortetracycline complexing compound in an amount sufficient to produce fermentation broth containing complexed chlortetracycline;

(c) lowering the pH of said second quantity of fermentation broth to a level sufficient to dissolve the chlortetracycline in said second quantity of fermentation broth;

(d) removing solids from said pH-adjusted second quantity of fermentation broth and collecting liquid containing dissolved chlortetracycline;

(e) adjusting the pH of said liquid containing dissolved chlortetracycline to a value of about 7 or greater and adding a chlortetracycline complexing compound in an amount sufficient to produce a suspension of complexed chlortetracycline;

(f) mixing said fermentation broth containing complexed chlortetracycline from step (b) and said suspension of complexed chlortetracycline from step (e);

(g) removing liquids from the mixture of step (f) to produce a complexed chlortetracycline-containing fermentation product having a low moisture content; and

(h) sizing said low moisture content fermentation product to produce a particulate chlortetracycline-containing fermentation product having a predetermined particle size or range of particle sizes.

71. A composition according to claim 70, wherein the ratio of said first quantity of fermentation broth to said second quantity of fermentation broth is from about 1:

10 to about 10;

1.

72. A composition according to claim 70, wherein the ratio of said first quantity of fermentation broth to said second quantity of fermentation broth is from about 1:

5 to about 5;

1.

73. A composition according to claim 70, wherein the ratio of said first quantity of fermentation broth to said second quantity of fermentation broth is from about 1:

3 to about 3;

1.

74. A composition according to claim 70, wherein the first quantity of fermentation broth and the second quantity of fermentation broth are from the same fermentation batch.

75. A composition according to claim 70, wherein the first quantity of fermentation broth and the second quantity of fermentation broth are from different fermentation batches.

76. A composition according to claim 70, wherein the chlortetracycline complexing compound added to said first quantity of fermentation broth is calcium carbonate.

77. A composition according to claim 70, wherein the pH of the first quantity of fermentation broth is adjusted by the addition of aqueous ammonia.

78. A composition according to claim 70, wherein the pH of the first quantity of fermentation broth is adjusted to a value of from about 7.5 to about 8.0.

79. A composition according to claim 70, wherein the pH of the second quantity of fermentation broth is adjusted by adding a mineral acid.

80. A composition according to claim 70, wherein the pH of the second quantity of fermentation broth is adjusted by adding one or more acids selected from the group consisting of oxalic acid, hydrochloric acid, and sulfuric acid.

81. A composition according to claim 70, wherein the pH of the second quantity of fermentation broth is adjusted to a value of about 4.0 or less.

82. A composition according to claim 70, wherein the pH of the second quantity of fermentation broth is adjusted to a value of about 2.0 or less.

83. A composition according to claim 70, wherein the pH of the second quantity of fermentation broth is adjusted to a value of about 1.0 to about 1.3.

84. A composition according to claim 70, wherein said chlortetracycline complexing compound added to said liquid containing dissolved chlortetracycline is calcium carbonate and the pH of said liquid containing dissolved chlortetracycline is adjusted by the addition of aqueous ammonia.

85. A composition according to claim 70, wherein the pH of said liquid containing dissolved chlortetracycline is adjusted to a pH of from about 7.5 to about 8.0.

86. A composition according to claim 70, wherein the removal of liquids in step (g) utilizes one or more of the following:

a filter press, centrifugal filter, rotary vacuum filter, oven, tray dyer, tunnel dryer, spray dryer, spray granulator, fluid bed dryer, shelf dryer, drum dryer, rotary dryer, microwave dryer, and contact dryer.

87. A composition according to claim 70, wherein the removal of liquids in step (g) utilizes at least one of:

a filter press, a centrifuge, and an oven.

88. A composition according to claim 70, wherein said filter cake is dried to a moisture content of from about 2% to about 12%.

89. A composition according to claim 70, wherein said filter cake is dried to a moisture content of from about 2% to about 6%.

90. A composition according to claim 70, wherein said low moisture content fermentation product comprises chlortetracycline in an amount from about 30% to about 75%.

91. A composition according to claim 70, wherein said solid having low moisture content comprises chlortetracycline in an amount from about 35% to about 65%.

92. A composition according to claim 70, wherein said solid having low moisture content comprises chlortetracycline in an amount from about 44% to about 55%.

93. A composition according to claim 70, wherein said particles are in the form of a powder, meal, pellets, granules, or tablets.

94. A composition according to claim 70, wherein said particles have a diameter of from about 150 μ

m to about 2 mm.

95. A composition according to claim 70, wherein said particles are produced without any compression or compaction step.

96. A composition according to claim 70, wherein said particles are produced with a compression or compaction step.

97. A composition according to claim 70, further comprising the step of blending said particulate chlortetracycline-containing fermentation product with at least one diluent selected from the group consisting of an edible feed material, a mineral product, and an oil.

98. A composition according to claim 97, further comprising the step of admixing said granules with a nonmedicated animal feedstuff.

99. A composition according to claim 97, wherein said edible feed material is rice hulls.

100. A composition according to claim 97, wherein said mineral product is limestone.

101. A composition according to claim 97, wherein said oil is mineral.

104. A composition according to claim 70, wherein the fermentation product has a sufficient antibiotic activity to treat an animal.