POLYMERIC ARTIFICIAL TEAR SYSTEM

• US 20120070402A1
• Filed: 11/22/2011
• Published: 03/22/2012
• Est. Priority Date: 04/26/2008
• Status: Active Grant

• Current Assignee: Alcon Research, LLC (Alcon Incorporated)
• Original Assignee: Alcon Research Limited (Nestle SA)
• Inventors: Ketelson, Howard Allen, Davis, James W., Meadows, David L.
• Granted Patent: US 8,685,945 B2
• Time in Patent Office: Days
• US Class Current: 424/78.04
• CPC Class Codes: A61K 31/08 acyclic, e.g. paraformaldehyde
• CPC Class Codes: A61K 31/736 Glucomannans or galactomannans, e.g. locust bean gum, guar gum
• CPC Class Codes: A61K 47/02 Inorganic compounds
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 47/26 Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
• CPC Class Codes: A61K 47/36 Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
• CPC Class Codes: A61K 9/0048 Eye, e.g. artificial tears
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 27/04 Artificial tears; Irrigation solutions

Abstract

The present invention relates to artificial tear formulations and ophthalmic formulations suitable for drug delivery. The formulations comprise galactomannans such as guar or hydroxypropyl guar and a borate source such as boric acid. The formulations further comprise a cis-diol such as sorbitol that interferes with the cross-linking of galactomannan and borate. Optionally, the formulations are substantially free of divalent cations.

Claims

1. An ophthalmic formulation comprising a galactomannan, borate, and a cis-diol, wherein said formulation is substantially free of divalent cations.

2. A formulation according to claim 1 wherein said galactomannan is present at a concentration of about 0.1 w/v % to about 2.0 w/v % and said borate is present at a concentration of about 0.2 w/v % to about 2.0 w/v %.

3. A formulation according to claim 1 wherein said galactomannan is present at a concentration of about 0.16 w/v % to about 0.19 w/v % and said borate is present at a concentration of about 0.7 w/v %.

4. A formulation according to claim 1 wherein said galactomannan is selected from the group consisting of:

guar, hydroxylpropyl guar, and combinations thereof.

5. A formulation according to claim 1 wherein said cis-diol is selected from the group consisting of sorbitol, mannitol, polyethylene glycols, polypropylene glycols, polyethyleneoxide-polybutyleneoxide block copolymers, and combinations thereof.

6. A formulation according to claim 1 wherein said cis-diol is sorbitol or mannitol.

7. A formulation according to claim 6 wherein said cis-diol is present at a concentration of about 1.4 w/v %.

8. A formulation according to claim 1 wherein said borate is boric acid.

9. A formulation according to claim 1 further comprising a demulcent selected from the group consisting of:

glycerin, polyvinyl pyrrolidone, polyethylene oxide, polyethylene glycol, propylene glycol, polyacrylic acid, and combinations thereof.

10. A formulation according to claim 9 wherein said demulcent is polypropylene glycol or polyethylene glycol.

13. A method for lubricating the eye comprising administering to the eye a formulation of claim 1.

14. A method for delivering a pharmaceutically active agent to the eye comprising:

administering to the eye a formulation of claim 1 further comprising a pharmaceutically active agent.

11. In an ophthalmic formulation comprising a galactomann and borate, the improvement comprising adding a cis-diol to prevent galactomann and borate cross-linking, thereby reducing the viscosity of the formulation.

12. A formulation according to claim 11, said formulation further being substantially free of divalent cations, thereby reducing the viscosity of the formulation.

15. An improved ophthalmic formulation comprising galactomannan and borate, said formulation comprising a cis-diol that is eliminated from tear film more rapidly than said galactomannan when the formulation is instilled in an eye.

16. An improved ophthalmic formulation according to claim 15 wherein said galactomannan is present at a concentration of about 0.16 w/v % to about 0.19 w/v % and said borate is present at a concentration of about 0.7 w/v %.

17. An improved ophthalmic formulation according to claim 16 wherein said galactomannan is selected from the group consisting of:

guar, hydroxylpropyl guar, and combinations thereof.

18. An improved ophthalmic formulation according to claim 15 wherein said cis-diol is selected from the group consisting of sorbitol, mannitol, polyethylene glycols, polypropylene glycols, polyethyleneoxide-polybutyleneoxide block copolymers, and combinations thereof.

19. An improved ophthalmic formulation according to claim 18 wherein said cis-diol is sorbitol or mannitol.

20. An improved ophthalmic formulation according to claim 15, said formulation further being substantially free of divalent cations, thereby reducing the viscosity of the formulation.

21. An improved ophthalmic formulation according to claim 15, said formulation further comprising a demulcent selected from the group consisting of:

glycerin, polyvinyl pyrrolidone, polyethylene oxide, polyethylene glycol, propylene glycol, polyacrylic acid, and combinations thereof.