Novel anti-inflammatory androstane derivative compositions

• US 20040224932A1
• Filed: 06/08/2004
• Published: 11/11/2004
• Est. Priority Date: 08/05/2000
• Status: Abandoned Application

• Current Assignee: Andrew L. Theophilus, Andrew S. Craig, Brian M. Noga, David M. Crowe, John F. Seager, Keith Biggadike, Michael J. Millan, Rosalyn K. Nice, Steven John Coote, Victor Jacewicz
• Original Assignee: Andrew L. Theophilus, Andrew S. Craig, Brian M. Noga, David M. Crowe, John F. Seager, Keith Biggadike, Michael J. Millan, Rosalyn K. Nice, Steven John Coote, Victor Jacewicz
• Inventors: Noga, Brian M., Biggadike, Keith, Coote, Steven John, Theophilus, Andrew L., Jacewicz, Victor, Seager, John F., Millan, Michael J., Nice, Rosalyn K., Crowe, David M., Craig, Andrew S.
• Application Number:
  US10/863,878
• Publication Number:
  US 20040224932A1
• Time in Patent Office: Days
• US Class Current: 514/172
• 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 37/08 Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 5/44 Glucocorticosteroids; Drugs increasing or potentiating the activity of glucocorticosteroids
• CPC Class Codes: C07J 17/00 Normal steroids containing carbon, hydrogen, halogen or oxygen, having an oxygen-containing hetero ring not condensed with the cyclopenta(a)hydrophenanthrene skeleton cardanolide, bufanolide C07J19/00
• CPC Class Codes: C07J 31/00 Normal steroids containing one or more sulfur atoms not belonging to a hetero ring

Abstract

There is provided a crystalline chemical composition comprising a compound of formula (I)

in which the crystal lattice is stabilised by the presence of a guest molecule, characterised in the crystalline composition is of space group P2₁2₁2₁ having unit cell dimensions of about 12.1±0.6 Å, 14.9±0.7 Å, and 16.2±0.8 Å when determined at either 120K or 150K.

Claims

1. A crystalline chemical composition comprising a compound of formula (I)

2. The composition of claim 1, which exhibits XRPD profiles (i)-(v).

3. A crystalline chemical composition comprising a compound of formula

4. The composition of claim 3, which exhibits both of XRPD profiles (i) and (ii).

5. A crystalline chemical composition comprising a compound of formula (I)

6. A crystalline chemical composition comprising a compound of formula (I)

7. A crystalline chemical composition comprising a compound of formula (I)

8. A crystalline chemical composition comprising a compound of formula (I)

9. A crystalline chemical composition comprising a compound of formula (I)

10. A crystalline chemical composition comprising a compound of formula (I)

11. A crystalline chemical composition comprising a compound of formula (I)

12. The composition according to claim 11, wherein the composition is a dry powder.

13. The composition according to claim 11, wherein the composition is a spray.

14. A crystalline chemical composition comprising a compound of formula (I)

19. The composition according to claim 14, which contains lactose or starch as the diluent or carrier.

15. A crystalline chemical composition comprising a compound of formula (I)

16. A crystalline chemical composition comprising a compound of formula (I)

17. The composition according to claim 16, wherein said anti-histamine is methapyrilene or loratadine, said anti-inflammatory agent is an NSAID and said antiinfective agent is an antibiotic or antiviral.

18. A crystalline chemical composition comprising a compound of formula (I)

20. A pharmaceutical composition comprising a crystalline chemical composition comprising a compound of formula (I)

21. A pharmaceutical aerosol formulation comprising a crystalline chemical composition comprising a compound of formula (I)

24. A pharmaceutical aerosol formulation according claim 21, wherein the propellant is selected from the group consisting of 1,1,1,2-tetrafluoroethane, 1,1,1,2,3,3,3-heptafluoro-n-propane and mixtures thereof.

25. A pharmaceutical aerosol formulation according to claim 21, which consists essentially of a compound of formula (I) optionally in combination with another therapeutically active agent and a propellant selected from 1,1,1,2-tetrafluoroethane, 1,1,1,2,3,3,3-heptafluoro-n-propane and mixtures thereof.

22. A pharmaceutical aerosol formulation comprising a crystalline chemical composition comprising a compound of formula (I)

23. A pharmaceutical aerosol formulation according to claim 22, wherein the suspending agent is an oligolactic acid.

26. The method for the treatment of a human or animal subject with an anti-inflammatory and/or allergic condition according to, which method comprises administering to said human or animal subject an effective amount of a crystalline chemical composition comprising a compound of formula (I)

27. The method for the treatment of a human or animal subject with an anti-inflammatory and/or allergic condition which method comprises administering to said human or animal subject an effective amount of a crystalline chemical composition comprising a compound of formula (I)

28. The method for the treatment of a human or animal subject with an anti-inflammatory and/or allergic condition which method comprises administering to said human or animal subject an effective amount of a crystalline chemical composition comprising a compound of formula (I)

29. The method of treatment of a human or animal subject with an anti-inflammatory and/or allergic condition which method comprises administering to said human or animal subject an effective amount of a crystalline chemical composition comprising a compound of formula (I)

30. The method of treatment of a human or animal subject with an anti-inflammatory and/or allergic condition which method comprises administering to said human or animal subject an effective amount of a crystalline chemical composition comprising a compound of formula (I)

31. A method for the treatment of at least one condition selected from the group consisting of skin disease, inflammatory condition of the nose, throat or lungs, inflammatory bowel condition, auto-immune disease, conjunctiva and conjunctivitis in a human or animal subject, which comprises administering an effective amount of a crystalline chemical composition comprising a compound of formula (I)

32. The method of treatment as recited in claim 31, wherein the skin disease is at least one selected from the group consisting of eczema, psoriasis, allergic dermatitis neurodermatitis, pruritis and hypersensitivity reactions.

33. The method of treatment as recited in claim 31, wherein the inflammatory condition of the nose, throat or lungs is at least one selected from the group consisting of asthma, rhinitis, nasal polyps, chronic obstructive pulmonary disease, interstitial lung disease and fibrosis.

34. The method of treatment as recited in claim 33, wherein the inflammatory condition of the nose, throat or lungs is asthma.

35. The method of treatment as recited in claim 33, wherein the inflammatory condition of the nose, throat or lungs is rhinitis.

36. The method of treatment as recited in claim 33, wherein the inflammatory condition of the nose, throat or lungs is chronic obstructive pulmonary disease.

37. The method of treatment as recited in claim 33, wherein the inflammatory bowel condition is at least one selected from the group consisting of ulcerative colitis and Crohn'"'"'s disease.

38. The method of treatment as recited in claim 31, wherein said composition is administered by inhalation or by nebulisation.

39. The method of treatment as recited in claim 31, wherein said composition is administered orally, buccally, sublingually, parenterally, locally or rectally.

40. The method for the treatment as recited in claim 31, wherein said effective amount of the composition is administered topically to said human or animal subject.

41. The method for the treatment as recited in claim 31, wherein said effective amount of the compound of formula (I) is administered topically as a dry powder to the lung via the buccal cavity.

42. The method for the treatment as recited in claim 31, wherein said effective amount of the compound of formula (I) is administered once per day.

43. An inhaler comprising a crystalline chemical composition comprising a compound of formula (I)

44. The inhaler of claim 43, further comprising propellant.

45. The inhaler of claim 43, further comprising at least one excipient selected from the group consisting of surfactant and cosolvent.

46. The inhaler of claim 43, wherein the composition is free of excipient.

47. The inhaler of claim 43, wherein the composition is retained in a pressurized canister closed with a valve.

48. The inhaler of claim 43, wherein said composition has a particle size in the range of 1-10 μ

m.

49. A process for preparing a crystalline chemical composition comprising a compound of formula (I)

50. The process of claim 49, wherein the compound of formula (I) is in the form of substantially amorphous particles.

51. A process for preparing a crystalline chemical composition comprising a compound of formula (I)

52. The process of claim 51, wherein the compound of formula (I) as crystalline unsolvated Form 1 polymorph is prepared by dissolving the compound of formula (I) in ethyl acetate and producing the compound of formula (I) as unsolvated Form 1 by addition of toluene as the anti-solvent.

53. A process for preparing a crystalline chemical composition comprising a compound of formula (I)