Use of borate-polyol complexes in ophthalmic compositions

• US 6,503,497 B2
• Filed: 12/19/2001
• Issued: 01/07/2003
• Est. Priority Date: 05/06/1992
• Status: Expired due to Fees

• Current Assignee: Alcon Research Limited (Nestle SA)
• Original Assignee: Alcon Manufacturing Limited (Alcon Incorporated)
• Inventors: Dassanayake, Nissanke L., Chowhan, Masood
• Primary Examiner(s): Dees, Jose' G.
• Assistant Examiner(s): HAGHIGHATIAN, MINA
• Application Number:
  US10/027,998
• Publication Number:
  US 20020098160A1
• Time in Patent Office: 384 Days
• Field of Search: 424/78.04, 424/427, 514/912, 514/839, 514/840
• US Class Current: 424/78.04
• CPC Class Codes: A61K 9/0048 Eye, e.g. artificial tears
• CPC Class Codes: Y10S 134/901 Contact lens

Abstract

Water-soluble borate-polyol complexes are useful as buffers and/or antimicrobials in aqueous ophthalmic compositions, including those containing polyvinyl alcohol. These compositions have greater antimicrobial activity than comparable compositions containing typical borate buffers and unexpectedly increase the antimicrobial efficacy of other antimicrobial agents when used in combination. In addition, use of the boratepolyol complexes avoids the incompatibility problem typically associated with the combination of borate buffer and polyvinyl alcohol; therefore, the compositions disclosed herein may also contain polyvinyl alcohol.

Claims

1. An aqueous ophthalmic composition comprising:

0.5 to 6.0 wt. % of a water soluble borate-polyol complex to enhance the antimicrobial activity of the composition, and water, said complex containing borate and polyol in a molar ratio of 1;

0.1 to 1;

10.

2. An aqueous ophthalmic composition according to claim 1, wherein the borate-polyol complex comprises a borate selected from the group consisting of boric acid, sodium borate, potassium borate, calcium borate, magnesium borate and manganese borate.

3. An aqueous ophthalmic composition according to claim 1, wherein the polyol is selected from the group consisting of mannitol, glycerin, propylene glycol and sorbitol.

4. An aqueous ophthalmic composition according to claim 3, wherein the polyol comprises mannitol.

5. An aqueous ophthalmic composition according to claim 3, wherein the polyol comprises glycerin.

6. An aqueous ophthalmic composition according to claim 3, wherein the polyol comprises propylene glycol.

7. An aqueous ophthalmic composition according to claim 3, wherein the polyol comprises sorbitol.

8. An aqueous ophthalmic composition according to any one of claims 1 to 7, wherein the borate-polyol complex is included in the composition at a concentration of 1.0 to 2.5 wt. %.

9. An aqueous ophthalmic composition according to any one of claims 1 to 7, wherein the molar ratio of borate to polyol is 1:

0.25 to 1;

2.5.

10. An aqueous ophthalmic composition according to any one of claims 1 to 7, wherein the molar ratio of borate to polyol is 1:

0.1 to 1;

1.

11. An aqueous ophthalmic composition according to any one of claims 1 to 7, wherein the molar ratio of borate to polyol is 1:

0.25 to 1;

0.75.

12. An aqueous ophthalmic composition according to any one of claims 1 to 7, wherein the borate-polyol complex is included in the composition at a concentration of 1.0 to 2.5 wt. %, and the molar ratio of borate to polyol is 1:

0.25 to 1;

2.5.

13. An aqueous ophthalmic composition according to any one of claims 1 to 7, wherein the borate-polyol complex comprises boric acid.

14. An aqueous ophthalmic composition according to claim 13, wherein the borate-polyol complex is included in the composition at a concentration of 1.0 to 2.5 wt. %, and the molar ratio of borate to polyol is 1:

0.1 to 1;

1.

15. An aqueous ophthalmic composition according to any one of the claims 1 to 7, wherein the borate-polyol complex comprises boric acid and sodium borate.

16. An aqueous ophthalmic composition according to claim 15, wherein the borate-polyol complex is included in the composition at a concentration of 1.0 to 2.5 wt. %, and the molar ratio of borate to polyol is 1:

0.1 to 1;

1.

17. An aqueous ophthalmic composition according to any one of claims 1 to 7, wherein the composition further comprises a preservative effective amount of an ophthalmically acceptable antimicrobial agent.

18. An aqueous ophthalmic composition according to claim 17, wherein the antimicrobial agent comprises polyquaternium-1.

19. An aqueous ophthalmic composition according to any one of claims 1 to 7, wherein the composition does not contain an ophthalmically acceptable antimicrobial agent.

20. An aqueous ophthalmic composition according to claim 8, wherein the composition is unpreserved.

21. An aqueous, unpreserved ophthalmic solution comprising an amount of a water soluble borate-polyol complex effective to enhance the antimicrobial activity of the solution.

22. An aqueous ophthalmic solution comprising:

0.5 to 6.0 wt. % of a water soluble borate-polyol complex to enhance the antimicrobial activity of the solution, and water, said borate-polyol complex comprising borate and glycerin in a molar ratio of 1;

0.1 to 1;

10.

23. An aqueous ophthalmic solution according to claim 22, wherein the solution further comprises an effective amount of a viscosity enhancing polymer.

24. An aqueous ophthalmic solution according to claim 23, wherein the viscosity-enhancing polymer comprises a cellulosic polymer.

25. An aqueous ophthalmic solution according to claim 24, wherein the cellulosic polymer comprises hydroxypropyl methylcellulose.

26. An aqueous ophthalmic solution according to any one of claims 22 to 25, wherein the solution further comprises a preservative effective amount of an ophthalmically acceptable antimicrobial agent.

27. An aqueous ophthalmic solution according to claim 26, wherein the ophthalmically acceptable antimicrobial agent comprises polyquaternium-1.

28. An aqueous ophthalmic solution according to any one of claims 22 to 25, wherein the solution does not contain an ophthalmically acceptable antimicrobial agent.

29. An aqueous ophthalmic solution according to any one of claims 22 to 25, wherein the solution contains the borate-polyol complex in an amount of 1.0 to 2.5 wt. %.

30. An aqueous ophthalmic solution according to claim 29, wherein the molar ratio of borate to polyol is 1:

0.1 to 1;

1.

31. An aqueous ophthalmic solution according to claim 29, wherein the molar ratio of borate to polyol is 1:

0.25 to 1;

2.5.

32. An aqueous ophthalmic solution according to claim 29, wherein the solution is unpreserved.

33. An aqueous ophthalmic solution comprising:

0.5 to 6.0 wt. % of a water soluble borate-polyol complex to enhance the antimicrobial activity of the solution, and water, wherein the borate-polyol complex comprises borate, propylene glycol and sorbitol and the molar ratio of borate to polyol is 1;

0.1 to 1;

10.

34. An aqueous ophthalmic solution according to claim 33, wherein the solution further comprises an effective amount of a viscosity-enhancing polymer.

35. An aqueous ophthalmic solution according to claim 34, wherein the viscosity-enhancing polymer comprises a cellulosic polymer.

36. An aqueous ophthalmic solution according to claim 35, wherein the cellulosic polymer comprises hydroxypropyl methylcellulose.

37. An aqueous ophthalmic solution according to any of claims 33 to 36, wherein the solution further comprises a preservative effective amount of an ophthalmically acceptable antimicrobial agent.

38. An aqueous ophthalmic solution according to claim 37, wherein the ophthalmically acceptable antimicrobial agent comprises polyquaternium-1.

39. An aqueous ophthalmic solution according to any one of claims 33 to 36, wherein the solution does not contain an ophthalmically acceptable antimicrobial agent.

40. An aqueous ophthalmic solution according to any one of claims 33 to 36, wherein the solution contains the borate-polyol complex in an amount of 1.0 to 2.5 wt. %.

41. An aqueous ophthalmic solution according to claim 40, wherein the molar ratio of borate to polyol is 1:

0.1 to 1;

1.

42. An aqueous ophthalmic composition according to claim 40, wherein the molar ratio of borate to polyol is 1:

0.25 to 1;

2.5.

43. An aqueous ophthalmic solution according to claim 40, wherein the solution is unpreserved.

44. An aqueous ophthalmic solution comprising:

a viscosity-enhancing amount of hydroxypropyl methylcellulose;

1.0 to 2.5 wt. % of a borate-polyol complex, said complex comprising boric acid and glycerin in a molar ratio of 1;

0.1 to 1;

1;

0.001 w/v % of polyquaternium-1; and

water.

45. An aqueous, unpreserved ophthalmic solution comprising:

a viscosity-enhancing effective amount of hydroxypropyl methylcellulose;

1.0 to 2.5 wt. % of a borate-polyol complex comprising boric acid, propylene glycol and sorbitol, wherein the molar ratio of borate to polyol is 1;

0.1 to 1;

1; and

water.