Methods for reducing or preventing transplant rejection in the eye and intraocular implants for use

• US 20050249710A1
• Filed: 07/11/2005
• Published: 11/10/2005
• Est. Priority Date: 11/29/2000
• Status: Active Grant

• Current Assignee: Allergan Incorporated (Abbvie Incorporated)
• Original Assignee: Allergan Incorporated (Abbvie Incorporated)
• Inventors: Wong, Vernon G.
• Granted Patent: US 7,767,223 B2
• Time in Patent Office: Days
• US Class Current: 424/93.700
• CPC Class Codes: A61F 2210/0004 bioabsorbable
• CPC Class Codes: A61F 9/0008 Introducing ophthalmic products into the ocular cavity or retaining products therein putting in contact lenses A61F9/0061; introducing or retaining media in cavities of the body in general A61M31/00
• CPC Class Codes: A61F 9/0017 implantable in, or in contact with, the eye, e.g. ocular inserts
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/56 Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
• CPC Class Codes: A61K 31/573 substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
• CPC Class Codes: A61K 31/715 Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
• CPC Class Codes: A61K 31/765 Polymers containing oxygen
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• 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 9/0048 Eye, e.g. artificial tears
• CPC Class Codes: A61K 9/0051 Ocular inserts, ocular implants
• CPC Class Codes: A61K 9/1641 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poloxamers
• CPC Class Codes: A61K 9/1647 Polyesters, e.g. poly(lactide-co-glycolide)
• CPC Class Codes: A61L 2300/222 Steroids, e.g. corticosteroids
• CPC Class Codes: A61L 2300/41 Anti-inflammatory agents, e.g. NSAIDs
• CPC Class Codes: A61L 2300/416 Anti-neoplastic or anti-proliferative or anti-restenosis or anti-angiogenic agents, e.g. paclitaxel, sirolimus
• CPC Class Codes: A61L 2300/604 Biodegradation
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61P 27/00 Drugs for disorders of the senses
• CPC Class Codes: A61P 27/02 : Ophthalmic agents
• CPC Class Codes: A61P 37/06 : Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 41/00 : Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system

Abstract

Methods for reducing or preventing transplant rejection in the eye of an individual are described, comprising: a) performing an ocular transplant procedure; and b) implanting in the eye a bioerodible drug delivery system comprising an immunosuppressive agent and a bioerodible polymer.

Claims

1. (canceled)

2. An intraocular, bioerodible drug delivery system comprising a steroid effective in preventing or reducing neovascularization in an eye prone to neovascularization, and a bioerodible polymer selected from the group consisting of hydroxyaliphatic carboxylic acids, and polysaccharides, thereby forming an implant for placement in the interior of an eye prone to neovascularization.

3. The drug delivery system of claim 2 wherein the steroid is dexamethasone.

4. The drug delivery system of claim 2 which includes no release modifier.

5. The drug delivery system of claim 2, wherein the steroid comprises about 10% to 90% of the weight of the drug delivery system.

6. The drug delivery system of claim 2, wherein the steroid is the sole active ingredient for preventing or reducing the neovascularization.

7. The drug delivery system of claim 2, wherein the bioerodible polymer comprises a polymer of D-lactic acid.

8. The drug delivery system of claim 2, wherein the bioerodible polymer comprises a polymer of L-lactic acid.

9. The drug delivery system of claim 2, wherein the bioerodible polymer comprises a polymer of racemic lactic acid.

10. The drug delivery system of claim 2, wherein the bioerodible polymer comprises a polymer of glycolic acid.

11. The drug delivery system of claim 2, wherein the bioerodible polymer comprises a polymer of polycaprolactone.

12. The drug delivery system of claim 2, wherein the bioerodible polymer comprises a calcium alginate.

13. The drug delivery system of claim 2, wherein the bioerodible polymer comprises a polymer of carboxymethylcellulose esters.

14. The drug delivery system of claim 2, wherein the bioerodible polymer comprises a polymer of hydroxypropyl methylcellulose.

15. An intraocular, bioerodible drug delivery system comprising

particles of a drug selected from the group consisting of immunosuppressive agents, antibacterial antibiotics, synthetic antibacterials, antifungal antibiotics, synthetic antifungal agents, antineoplastic agents, steroidal anti-inflammatory agents, non-steroidal anti-inflammatory agents, and combinations thereof, and

a polylactic acid polyglycolic acid (PLGA) copolymer,

wherein the system is effective in releasing the drug into the eye over a period of at least about 5 days, and wherein the intraocular, bioerodible drug delivery system is a single pellet or a single extruded filament.

16. The system of claim 15, wherein the system is effective in releasing the drug into the eye over a period of at least about 2 weeks.

17. The system of claim 15, wherein the system is effective in releasing the drug into the eye over a period of at least about 3 weeks.

18. The system of claim 15, wherein the system is effective in releasing the drug into the eye over a period of at least about 4 weeks.

19. The system of claim 15, wherein the system is effective in releasing the drug into the eye over a period of at least about 5 weeks.

20. The system of claim 15, wherein the system is effective in releasing the drug into the eye over a period of at least about 6 weeks.

21. The system of claim 15, wherein the system is effective in releasing the drug into the eye over a period of at least about 7 weeks.

22. The system of claim 15, wherein the system is effective in releasing the drug into the eye over a period of at least about 8 weeks.

23. The system of claim 15, wherein the system is effective in releasing the drug into the eye over a period of at least about 9 weeks.

24. The system of claim 15, wherein the system is effective in releasing the drug into the eye over a period of at least about 10 weeks.

25. The system of claim 15, wherein the system is effective in releasing the drug into the eye over a period of at least about 12 weeks.

26. The system of claim 15, wherein the system is effective in releasing the drug into the eye over a period up to about 6 months.

27. The system of claim 15, wherein the system is effective in releasing the drug into the eye over a period up to 1 year.

28. A method for treating neovascularization and edema in an eye of an individual, comprising:

placing a bioerodible drug delivery system comprising an immunosuppressive agent and a bioerodible polymer in an eye of an individual, thereby treating neovascularization and edema of the eye of the individual.

29. The method of claim 28, wherein the placing comprises placing the bioerodible drug delivery system in the vitreous of the eye.

30. The method of claim 28, wherein the bioerodible drug delivery system comprises dexamethasone.

31. The method of claim 28, wherein the bioerodible polymer comprises a polylactic acid polyglycolic acid (PLGA) copolymer.

32. The method of claim 28, wherein the bioerodible drug delivery system delivers the immunosuppressive agent for at least about 5 days.

33. The method of claim 28, wherein the bioerodible drug delivery system delivers the immunosuppressive agent for at least about 3 weeks.

34. A method for treating edema in an eye of an individual, comprising:

placing a bioerodible drug delivery system comprising an immunosuppressive agent and a bioerodible polymer in an eye of an individual, thereby treating edema of the eye of the individual.

35. The method of claim 34, wherein the placing comprises placing the bioerodible drug delivery system in the vitreous of the eye.

36. An intraocular, bioerodible drug delivery system comprising a drug effective in preventing or reducing edema in an eye prone to edema, and a bioerodible polymer.

37. The drug delivery system of claim 36, wherein the drug is a steroid.

38. The drug delivery system of claim 36, wherein the drug is dexamethasone.

39. The drug delivery system of claim 36 which includes no release modifier.

40. The drug delivery system of claim 36, wherein the drug comprises about 10% to 90% of the weight of the drug delivery system.

41. The drug delivery system of claim 36, wherein the drug is the sole active ingredient for preventing or reducing the edema.