CONTROLLED-RELEASE OPHTHALMIC VEHICLES

• US 20100226997A1
• Filed: 03/05/2009
• Published: 09/09/2010
• Est. Priority Date: 03/05/2009
• Status: Active Grant

• Current Assignee: Sun Pharma Global Fze (Sun Pharmaceutical Industries Limited)
• Original Assignee: Insite Vision Incorporated (Daiichi Sankyo Company Limited)
• Inventors: Pham, Stephen, Bowman, Lyle
• Granted Patent: US 8,501,800 B2
• Time in Patent Office: Days
• US Class Current: 424/501
• CPC Class Codes: A61K 47/32 Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers , poly(meth)acrylates, or polyvinyl pyrrolidone
• CPC Class Codes: A61K 47/34 Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers A61K47/10 takes precedence
• 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

Abstract

An ophthalmically acceptable vehicle includes an aqueous suspension having a first viscosity. The suspension includes about 0.1% to about 6.5% by weight of a carboxyl-containing polymer prepared by polymerizing one or more carboxyl-containing monoethylenically unsaturated monomers and less than about 5% by weight of a cross-linking agent. The polymer has average particle size of not more than about 50 μm in equivalent spherical diameter. The vehicle includes a second polymer that allows the carboxyl-containing polymer to remain suspended. Upon contact with tear fluid, the vehicle gels to a second viscosity which is greater than the first viscosity. A method of administering a medicament to the eye of a subject includes applying a composition that includes this ophthalmically acceptable vehicle and a medicament contained for treatment of a disease or disorder for which ophthalmic delivery is indicated. The medicament is released from the vehicle in a sustained release manner.

Claims

1. An ophthalmically acceptable vehicle, comprising:

an aqueous suspension having a first viscosity, said suspension comprising from about 0.1% to about 6.5% by weight, based on the total weight of the suspension, of a carboxyl-containing polymer prepared by polymerizing one or more carboxyl-containing monoethylenically unsaturated monomers and less than about 5% by weight of a cross-linking agent, said weight percentages of monomers being based on the total weight of monomers polymerized, said carboxyl-containing polymer having average particle size of not more than about 50 μ

m in equivalent spherical diameter, and

a sufficient amount of a second polymer allowing said carboxyl-containing polymer to remain suspended,

wherein upon contact with tear fluid, said vehicle gels to a second viscosity which is greater than the first viscosity.

2. The vehicle of claim 1, wherein the second polymer is a neutral polymer.

3. The vehicle of claim 2, wherein the neutral polymer is selected from the group consisting of polyvinyl alcohol and polyethylene oxide.

4. The vehicle of claim 1, wherein the second polymer is an anionic polymer.

5. The vehicle of claim 4, wherein the anionic polymer is polyacrylic acid.

6. The vehicle of claim 1, wherein the second polymer is a cationic polymer.

7. The vehicle of claim 6, wherein the cationic polymer is selected from the group consisting of polyglycine, poly-L-lysine, chitosan, Polyquaternium 1, Polyquaternium 7, Polyquarternium 10, and polyethyleneimine.

8. The vehicle of claim 7, wherein the cationic polymer is chitosan.

9. The vehicle of claim 8, where chitosan has a molecular weight in a range from between about 50 kDa to about 100 kDa.

10. The vehicle of claim 8, wherein chitosan is present in a range from between about 0.01% to about 5.0% by weight.

11. The vehicle of claim 8, wherein chitosan has a molecular weight in a range from between about 500 kDa to about 3,000 kDa.

12. The vehicle of claim 8, wherein chitosan is present in a range from between about 0.01% and about 0.05% by weight.

13. A composition comprising the ophthalmically acceptable vehicle of claim 1 and a medicament for treatment of a disease or disorder, wherein ocular delivery of said medicament is indicated for the treatment of said disease or disorder.

14. The composition of claim 13, wherein the second polymer is selected from the group consisting of polyglycine, poly-L-lysine, chitosan, Polyquaternium 1, Polyquaternium 7, Polyquaternium 10, and polyethyleneimine.

15. The composition of claim 14, wherein the second polymer is chitosan.

16. The composition of claim 15, wherein chitosan has a molecular weight in a range from between about 50 kDa to about 100 kDa.

17. The composition of claim 16, wherein chitosan is present in a range from between about 0.01% to about 5.0% by weight.

18. The composition of claim 15, wherein chitosan has a molecular weight in a range from between about 1,000 kDa to about 3,000 kDa.

19. The composition of claim 18, wherein chitosan is present in a range from between about 0.01% and about 0.05%.

20. The composition of claim 13, wherein an osmotic pressure is achieved using a physiologically and ophthalmologically acceptable salt in an amount of from about 0.01% to about 1% by weight, based on the total weight of the suspension.

21. The composition of claim 13, wherein said medicament is present in an amount of from about 0.005% to about 10% by weight, based on the total weight of the suspension.

22. The composition of claim 13, wherein said medicament is selected from the group consisting of an antibacterial antibiotic agent, an antibacterial agent, an antifungal antibiotic agent, an antifungal agent, an antineoplastic agent, a steroidal anti-inflammatory agents, a non-steroidal anti-inflammatory agent, an anti-allergic agent, a glaucoma-treating agent, an antiviral agent, an anti-mycotic agent, an anti-infective agent, an anti-allergic agent, an antiviral agent, an anti-glaucoma agent, an anesthetic agent, a retinal like anti-angiogenesis agent, an agent to treat AMD, an agent to treat diabetic retinopathy, an agent to treat macular edema, and combinations thereof.

23. The composition of claim 22, having at least two medicaments.

24. The composition of claim 23, wherein said at least two medicaments are different non-steroidal anti-inflammatory agents.

25. The composition of claim 23, wherein said at least two medicaments are a non-steroidal anti-inflammatory agent and a steroidal anti-inflammatory agent.

26. The composition of claim 13 further comprising a preservative.

27. The composition of claim 13 further comprising a thickener.

28. The composition of claim 13 further comprising a wetting agent.

29. A method of administering a medicament to the eye of a subject comprising applying to the eye of a subject a composition comprising the ophthalmically acceptable vehicle of claim 1 and a medicament contained therein for treatment of a disease or disorder for which ophthalmic delivery is indicated;

wherein said medicament is released from the vehicle in a sustained release manner.