Compositions containing therapeutically active components having enhanced solubility

• US 20020071874A1
• Filed: 07/10/2001
• Published: 06/13/2002
• Est. Priority Date: 07/14/2000
• Status: Active Grant

• Current Assignee: Allergan, Inc. (Canada) (Abbvie Incorporated)
• Original Assignee: Allergan Sales LLC (Abbvie Incorporated)
• Inventors: Olejnik, Orest, Kerslake, Edward D.S.
• Granted Patent: US 6,562,873 B2
• Time in Patent Office: Days
• US Class Current: 424/661
• CPC Class Codes: A61K 31/4164 1,3-Diazoles
• CPC Class Codes: A61K 31/498 Pyrazines or piperazines ortho- and peri-condensed with carbocyclic ring systems, e.g. quinoxaline, phenazine
• CPC Class Codes: A61K 9/0048 Eye, e.g. artificial tears
• CPC Class Codes: A61P 25/02 for peripheral neuropathies
• CPC Class Codes: A61P 27/00 Drugs for disorders of the senses
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

Compositions which include therapeutically active components, solubility enhancing components other than cyclodextrins, and oxy-chloro components, wherein the oxy-chloro components are substantially effective as preservatives. In one embodiment, the oxy-chloro components are useful for preserving the therapeutically active components. In one embodiment, the oxy-chloro components include chlorite components. In a useful embodiment, the solubility enhancing components include carboxymethylcellulose.

Claims

1. A composition comprising:

a therapeutically active component in an amount effective to provide a desired therapeutic benefit to a patient to whom the composition is administered;

a solubility enhancing component, other than a cyclodextrin, in an amount effective to increase the solubility of the therapeutically active component in the composition relative to the solubility of an identical therapeutically active component in a similar composition without the solubility enhancing component;

an oxy-chloro component in an effective amount to at least aid in preserving the composition; and

a liquid carrier component.

2. The composition of claim 1 wherein the therapeutically active component is selected from the group consisting of antibacterials, antihistamines, decongestants, antiinflammatories, antiparasitics, miotics, anticholinergics, adrenergics, antivirals, local anesthetics, antifungals, amoebicidals, trichomonocidals, analgesics, mydriatics, antiglaucoma drugs, carbonic anhydrase inhibitors, ophthalmic diagnostic agents, ophthalmic agents used as adjuvants in surgery, chelating agents, antineoplastics, antihypertensives, muscle relaxants, diagnostics, derivatives thereof and mixtures thereof.

3. The composition of claim 1 wherein the therapeutically active component is selected from the group consisting of adrenergic agonists and mixtures thereof.

4. The composition of claim 1 wherein the therapeutically active component is selected from the group consisting of alpha-2-adrenergic agonists and mixtures thereof.

5. The composition of claim 1 wherein the therapeutically active component selected from the group consisting of imino-imidazolines, imidazolines, imidazoles, azepines, thiazines, oxazolines, guanidines, catecholamines, derivatives thereof and mixtures thereof.

6. The composition of claim 1 wherein the therapeutically active component includes a quinoxaline component.

7. The composition of claim 6 wherein the quinoxaline component is selected from the group consisting of quinoxaline, derivatives thereof, and mixtures thereof.

8. The composition of claim 6 wherein the quinoxaline component is selected from the group consisting of quinoxaline, (2-imidozolin-2-ylamino) quinoxaline, 5-bromo-6-(2-imidozolin-2-ylamino) quinoxaline, and tartrate of 5-bromo-6-(2-imidozolin-2-ylamino) quinoxaline, derivatives thereof and mixtures thereof.

9. The composition of claim 1 wherein the therapeutically active component comprises a tartrate of 5-bromo-6-(2-imidozolin-2-ylamino) quinoxaline.

10. The composition of claim 1 wherein the therapeutically active component has increased diffusion through a lipid membrane relative to an identical therapeutically active component in a similar composition without the solubility enhancing component.

11. The composition of claim 1 wherein the solubility enhancing component is effective to increase the solubility in a biological environment of the therapeutically active component relative to the solubility in a biological environment of an identical therapeutically active component in a similar composition without the solubility enhancing component.

12. The composition of claim 1 wherein the solubility enhancing component comprises a polyanionic component.

13. The composition of claim 12 wherein said polyanionic components is selected from the group consisting of anionic cellulose derivatives, anionic polymers derived from acrylic acid, anionic polymers derived from methacrylic acid, anionic polymers derived from alginic acid, anionic polymers derived from amino acids and mixtures thereof.

14. The composition of claim 1 wherein the solubility enhancing component is selected from the group consisting of anionic cellulose derivatives and mixtures thereof.

15. The composition of claim 1 wherein the solubility enhancing component is selected from the group consisting of carboxymethylcelluloses and mixtures thereof.

16. The composition of claim 1 wherein the solubility enhancing component is present in an amount in a range of about 0.1% (w/v) to about 30% (w/v).

17. The composition of claim 1 wherein the solubility enhancing component is present in an amount in a range of about 0.2% (w/v) to about 10 (w/v).

18. The composition of claim 1 wherein the solubility enhancing component is present in an amount in a range of about 0.2% (w/v) to about 0.6% (w/v).

19. The composition of claim 1 wherein the oxy-chloro component is selected from the group consisting of hypochlorite components, perchlorate components, chlorite components and mixtures thereof.

20. The composition of claim 1 wherein the oxy-chloro component comprises a chlorite component.

21. The composition of claim 1 wherein the oxy-chloro component comprises stabilized chlorine dioxide.

22. The composition of claim 1, wherein the oxy-chloro component is present in an amount of about 500 ppm (w/v) or less.

23. The composition of claim 1 wherein the oxy-chloro component is present in an amount in a range of about 10 ppm (w/v) to about 200 ppm (w/v).

24. The composition of claim 1 which further comprises an additional preservative component other than the oxy-chloro component in an amount effective to at least aid in preserving the composition.

25. The composition of claim 24, wherein the additional preservative component is selected from the group consisting of sorbic acid, benzalkonium chloride, chlorbutol and alkyl esters of p-hydroxybenzoic acid and mixtures thereof.

26. The composition of claim 1 wherein the liquid carrier is an aqueous liquid carrier component.

27. The composition of claim 1 which is a solution.

28. The composition of claim 1 which has a pH of about 7 or greater.

29. The composition of claim 1 which has a pH in a range of about 7 to about 9.

30. The composition of claim 1 which is ophthalmically acceptable.

31. A composition comprising:

a therapeutically active component selected from the group consisting of alpha-2-adrenergic agonists and mixtures thereof in an amount effective to provide a therapeutic benefit to a patient to whom the composition is administered;

an anionic cellulose derivative in an amount effective to increase the solubility of the therapeutically active component;

a chlorite component in an effective amount to at least aid in preserving the composition; and

an aqueous liquid carrier component.

32. The composition of claim 31 wherein the therapeutically active component comprises a tartrate of 5-bromo-6-(2-imidozolin-2-ylamino) quinoxaline.

33. The composition of claim 31 wherein the anionic cellulose derivative comprises carboxymethylcellulose.

34. The composition of claim 31 wherein the anionic cellulose derivative is present in an amount in a range of about 0.2% to about 0.6% (w/v).

36. The composition of claim 35 wherein the solubility enhancing component comprises a carboxymethylcellulose.

37. The composition of claim 35 which is ophthalmically acceptable.

39. The composition of claim 38 wherein the therapeutically active component is selected from the group consisting of antibacterials, antihistamines, decongestants, antiinflammatories, antiparasitics, miotics, anticholinergics, adrenergics, antivirals, local anesthetics, antifungals, amoebicidals, trichomonocidals, analgesics, mydriatics, antiglaucoma drugs, carbonic anhydrase inhibitors, ophthalmic diagnostic agents, ophthalmic agents used as adjuvants in surgery, chelating agents, antineoplastics, antihypertensives, muscle relaxants, diagnostics, derivatives thereof and mixtures thereof.

40. The composition of claim 38 wherein the therapeutically active component is selected from the group consisting of adrenergic agonists and mixtures thereof.

41. The composition of claim 38 wherein the therapeutically active component is selected from the group consisting of alpha-2-adrenergic agonists and mixtures thereof.

42. The composition of claim 38 wherein the therapeutically active component selected from the group consisting of imino-imidazolines, imidazolines, imidazoles, azepines, thiazines, oxazolines, guanidines, catecholamines, derivatives thereof and mixtures thereof.

43. The composition of claim 38 wherein the therapeutically active component includes a quinoxaline component.

44. The composition of claim 43 wherein the quinoxaline component is selected from the group consisting of quinoxaline, derivatives thereof, and mixtures thereof.

45. The composition of claim 43 wherein the quinoxaline component is selected from the group consisting of quinoxaline, (2-imidozolin-2-ylamino) quinoxaline, 5-bromo-6-(2-imidozolin-2-ylamino) quinoxaline, and tartrate of 5-bromo-6-(2-imidozolin-2-ylamino) quinoxaline, derivatives thereof and mixtures thereof.

46. The composition of claim 38 wherein the therapeutically active component comprises a tartrate of 5-bromo-6-(2-imidozolin-2-ylamino) quinoxaline.

47. The composition of claim 38, which further includes a solubility enhancing component, other than a cyclodextrin, in an amount effective to increase the solubility of the therapeutically active component in the composition relative to the solubility of an identical therapeutically active component in a similar composition without the solubility enhancing component.

48. The composition of claim 47 wherein the solubility enhancing component comprises a polyanionic component.

49. The composition of claim 38 wherein the oxy-chloro component is selected from the group consisting of hypochlorite components, perchlorate components, chlorite components and mixtures thereof.

50. The composition of claim 38 wherein the oxy-chloro component comprises a chlorite component.

51. The composition of claim 38 wherein the oxy-chloro component comprises stabilized chlorine dioxide.

52. The composition of claim 38 which is ophthalmically acceptable.

35. A composition comprising:

a tartrate of 5-bromo-6-(2-imidozolin-2-ylamino) quinoxaline in an amount effective to provide a therapeutic benefit to a patient to whom the composition is administered;

a solubility enhancing component in an amount effective to increase the solubility of the tartrate of 5-bromo-6-(2-imidozolin-2-ylamino) quinoxaline;

a chlorite component in an effective amount to at least aid in preserving the composition; and

an aqueous liquid carrier component.

38. A composition comprising:

a therapeutically active component in an amount effective to provide a desired therapeutic benefit to a patient to whom the composition is administered;

an oxy-chloro component in an effective amount to at least aid in preserving the composition; and

a liquid carrier component, wherein the composition is substantially free of cyclodextrins.