Controlled delivery of tetracycline compounds and tetracycline derivatives

• US 20040115261A1
• Filed: 10/03/2003
• Published: 06/17/2004
• Est. Priority Date: 04/05/2001
• Status: Abandoned Application

• Current Assignee: Galderma Laboratories Incorporated (Nestle SA)
• Original Assignee: Galderma Laboratories Incorporated (Nestle SA)
• Inventors: Ashley, Robert A.
• Application Number:
  US10/474,240
• Publication Number:
  US 20040115261A1
• Time in Patent Office: Days
• US Class Current: 424/468
• CPC Class Codes: A61K 31/166 having the carbon of a carboxamide group directly attached to the aromatic ring, e.g. procainamide, procarbazine, metoclopramide, labetalol
• CPC Class Codes: A61K 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 21/06 Anabolic agents androgens A61P5/26
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

A composition is provided for delivering a tetracycline compound to a mammal. The composition includes an antibiotic tetracycline compound and a controlled-release agent having at least one controlled-release agent. The tetracycline compound is associated with the controlled- release matrix to provide a release profile whereby the mammal is treated substantially without antibiotic activity. Methods for treating a mammal with a tetracycline compound and a dosage unit are also provided utilizing the controlled-release tetracycline composition.

Claims

1. A composition for delivering tetracycline compound to a mammal comprising:

a. an antibiotic tetracycline compound, and

b. at least one controlled-release agent;

said tetracycline compound associated with said at least one controlled-release agent to provide a tetracycline-release-profile in said mammal, whereby said mammal is treated with said tetracycline compound substantially without antibiotic activity.

2. A composition as described in claim 1 wherein said release profile provides a blood serum concentration level of said tetracycline compound in said mammal of about 0.1 μ

g/ml to about 1.0 μ

g/ml.

3. A composition as described in claim 2 wherein said release profile provides a blood serum concentration level of said tetracycline compound in said mammal of about 0.3 μ

g/ml to about 0.8 μ

g/ml.

4. A composition as described in claim 1 wherein said release profile is maintained at a substantially constant rate for between about 6-24 hours.

5. A composition as described in claim 1 wherein said antibiotic tetracycline compound is selected from the group consisting of tetracycline, doxycycline, demeclocycline, minocycline, and lymecycline.

6. A composition as described in claim 5 wherein said tetracycline compound is doxycycline.

7. A composition as described in claim 6 wherein said release profile provides a blood serum concentration level of said doxycycline in said mammal of about 0.4 μ

g/ml to about 0.8 μ

g/ml.

8. A composition as described in claim 1 wherein said controlled-release agent is selected from the group consisting of an instantaneous release agent, a sustained-release agent, a delayed-release agent, and combinations thereof.

9. A composition according to claim 8 wherein said instantaneous release agent is a surfactant.

10. A composition according to claim 8 wherein said sustained release agent is selected from the group consisting of gels, waxes, fats, emulsifiers, polymers, starch, cellulose polymers, and combinations thereof.

11. A composition according to claim 10 wherein said cellulose polymers are selected from the group consisting of hydroxypropyl methyl cellulose (HPMC), hydroxyethyl cellulose (HEC), hydroxypropyl cellulose (HPC), carboxy methyl cellulose (CMC), and mixtures thereof.

12. A composition according to claim 8 wherein said delayed release agent is selected from the group consisting of a polymeric or biodegradable coating or matrix, or combinations thereof.

13. A composition as described in claim 1 wherein said association between said tetracycline compound and said controlled-release agent is selected from the group consisting of physical association, chemical association and combinations thereof.

14. A method of treating a mammal with a tetracycline compound comprising administering to said mammal an antibiotic tetracycline compound associated with a controlled-release matrix having at least one controlled-release agent to provide a release profile having a nonantibiotic activity over a pre-selected time period.

15. A method as described in claim 14 wherein said release profile provides a blood serum concentration level of said tetracycline compound in said mammal of about 0.1 to about 1.0 μ

g/ml.

16. A method as described in claim 15 wherein said release profile provides a blood serum concentration level of said tetracycline compound in said mammal of about 0.3 to about 0.8 μ

g/ml.

17. A method as described in claim 14 wherein said release profile is maintained at a substantially constant rate for between about 6-24 hours.

18. A method as described in claim 14 wherein said antibiotic tetracycline compound is selected from the group consisting of tetracycline, doxycycline, demeclocycline, minocycline, and lymecycline.

19. A method as described in claim 18 wherein said tetracycline compound is doxycycline.

20. A method as described in claim 19 wherein said release profile provides a blood serum concentration level of said doxycycline in said mammal of about 0.4 μ

g/ml to about 0.8 μ

g/ml.

21. A method as described in claim 14 wherein said control release agent is selected from the group consisting of an instantaneous release agent, a sustained-release agent, a delayed-release agent, and combinations thereof.

22. A method according to claim 21 wherein said instantaneous release agent is a surfactant.

23. A method according to claim 21 wherein said sustained release agent is selected from the group consisting of gels, waxes, fats, emulsifiers, polymers, starch, cellulose polymers, and combinations thereof.

24. A method according to claim 23 wherein said cellulose polymers are selected from the group consisting of hydroxypropyl methyl cellulose (HPMC), hydroxyethyl cellulose (HEC), hydroxypropyl cellulose (HPC), carboxy methyl cellulose (CMC), and mixtures thereof.

25. A method according to claim 21 wherein said delayed release agent is selected from the group consisting of a polymeric or biodegradable coating or matrix, or combinations thereof.

26. A method as described in claim 14 wherein said association between said tetracycline compound and said controlled-release agent is selected from the group consisting of physical association, chemical association and combinations thereof.

27. A method according to claim 14 wherein said tetracycline compound associated with a controlled-release matrix having at least one controlled-release agent are formed into a tablet.

28. A method according to claim 14 wherein said administration to said mammal is enteral administration.

29. A unit dosage for controlled delivery of a tetracycline comprising:

a. an antibiotic tetracycline compound, and

b. at least one controlled-release agent; and

said tetracycline compound associated with said at least one controlled-release agent to provide a tetracycline-release-profile in said mammal, whereby said mammal is treated with said tetracycline substantially without antibiotic activity.

30. A unit dosage as described in claim 29 which is a capsule.

31. A unit dosage as described in claim 29 which is a tablet.

32. A unit dosage as described in claim 29 wherein said release profile provides a blood serum concentration level of said tetracycline compound in said mammal of about 0.1 μ

g/ml to about 1.0 μ

g/ml.

33. A unit dosage as described in claim 32 wherein said blood serum concentration level of said tetracycline compound in said mammal is between about 0.3 μ

g/ml to about 0.8 μ

g/ml.

34. A unit dosage as described in claim 29 wherein said release profile is maintained at a substantially constant rate for between about 6-24 hours.

35. A unit dosage as described in claim 29 wherein said antibiotic tetracycline compound is selected from the group consisting of tetracycline, doxycycline, demeclocycline, minocycline, and lymecycline.

36. A unit dosage as described in claim 35 wherein said tetracycline compound is doxycycline.

37. A unit dosage as described in claim 36 wherein said release profile provides a blood serum concentration level of said tetracycline compound in said mammal of about 0.4 μ

g/ml to about 0.8 μ

g/ml.