Use of borate-polyol complexes in ophthalmic compositions

• US 20020098160A1
• Filed: 12/19/2001
• Published: 07/25/2002
• Est. Priority Date: 05/06/1992
• Status: Active Grant

• Current Assignee: Alcon Research Limited (Nestle SA)
• Original Assignee: Masood Chowhan, Nissanke L. Dassanayake
• Inventors: Dassanayake, Nissanke L., Chowhan, Masood
• Granted Patent: US 6,503,497 B2
• Time in Patent Office: Days
• US Class Current: 424/78.26
• 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 borate-polyol 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 between about 0.5 and about 6.0 wt% of a water-soluble borate-polyol complex.

2. The aqueous composition of claim 1, wherein the water-soluble borate-polyol complex is present at a concentration between about 1.0 and 2.5 wt%.

3. The aqueous composition of claim 1, wherein the water-soluble borate-polyol complex comprises borate and polyol in a molar ratio between about 1:

0.1 and about 1 ;

10.

4. The aqueous composition of claim 3, wherein the water-soluble borate-polyol complex comprises borate and polyol in a molar ratio between about 1:

0.25 and about 1;

2.5.

5. The aqueous composition of claim 1, wherein the water-soluble borate-polyol complex comprises a polyol selected from the group consisting of sugars, sugar alcohols and sugar acids.

6. The aqueous composition of claim 2, wherein the polyol is selected from the group consisting of mannitol, glycerin, propylene glycol and sorbitol.

7. The aqueous composition of claim 6, wherein the polyol is selected from the group consisting of mannitol and glycerin.

8. The aqueous composition of claim 7, wherein the polyol is mannitol.

9. The aqueous composition of claim 1, further comprising less than or equal to about 10 wt% of a viscosity-enhancing polymer selected from the group consisting of:

polyvinyl alcohol, cellulosic polymers, and carboxy vinyl polymers.

10. The aqueous composition of claim 9, wherein the viscosity-enhancing polymer comprises polyvinyl alcohol.

11. The aqueous composition of claim 9, wherein the polyvinyl alcohol is present at a concentration between about 0.1 and about 1.4 wt%.

12. The aqueous composition of claim 1, further comprising an ophthalmically acceptable antimicrobial agent.

13. The aqueous composition of claim 1, wherein the ophthalmically acceptable antimicrobial agent is selected from the group consisting of:

monomeric and polymeric quaternary ammonium compounds and their ophthalmically acceptable salts, monomeric and polymeric biguanides and their ophthalmically acceptable salts, and combinations thereof.

15. The method of claim 14, wherein the water-soluble borate-polyol complex comprises borate and polyol in a molar ratio between about 1:

0.1 and about 1;

10.

16. The method of claim 15, wherein the water-soluble borate-polyol complex comprises borate and polyol in a molar ratio between about 1:

0.25 and about 1;

2.5.

17. The method of claim 14, wherein the concentration of the water-soluble borate-polyol complex in the final composition is between about 0.5 and about 3.0 wt%.

18. The method of claim 17, wherein the concentration of the water-soluble borate-polyol complex in the final composition is between about 1.0 and about 2.0 wt%.

19. The method of claim 14, wherein the water-soluble borate-polyol complex comprises a polyol selected from the group consisting of sugars, sugar alcohols and sugar acids.

20. The method of claim 19, wherein the polyol is selected from the group consisting of mannitol, glycerin, propylene glycol and sorbitol.

21. The method of claim 20, wherein the polyol is selected from the group consisting of mannitol and glycerin.

22. The method of claim 21, wherein the polyol is mannitol.

14. A method of preparing an aqueous ophthalmic composition, comprising the steps of preparing a water-soluble borate-polyol complex by mixing borate and a polyol together in an aqueous solvent and adding polyvinyl alcohol thereto.

23. A method for buffering an aqueous ophthalmic composition by adding a water-soluble borate-polyol complex to the composition.

24. A method for imparting antimicrobial activity to an ophthalmic composition by adding a water-soluble borate-polyol complex to the composition.