Ocular therapy using alpha-2 adrenergic receptor anterior compounds having enhanced clearance rates

• US 20060257452A1
• Filed: 05/02/2006
• Published: 11/16/2006
• Est. Priority Date: 05/10/2005
• Status: Active Grant

• Current Assignee: Allergan, Inc. (Canada) (Abbvie Incorporated)
• Original Assignee: Allergan, Inc. (Canada) (Abbvie Incorporated)
• Inventors: Hughes, Patrick M., Burke, James A., Chang-Lin, Joan-En
• Granted Patent: US 7,931,909 B2
• Time in Patent Office: Days
• US Class Current: 424/427
• 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 9/1647 Polyesters, e.g. poly(lactide-co-glycolide)
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 27/06 Antiglaucoma agents or miotics
• CPC Class Codes: A61P 27/10 for accommodation disorders, e.g. myopia
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

Ophthalmically therapeutic materials, such as liquid-containing compositions and polymeric drug delivery systems, include a therapeutic component which includes an alpha 2 adrenergic receptor agonist that is cleared from the anterior segment of an individual'"'"'s eye to which the material is administered. The alpha 2 adrenergic receptor agonist may have a vitreal half-life greater than about three hours. The present materials are effective in treating an ocular condition(s) that affect the anterior segment of an eye, or the anterior and posterior segment of the eye. The materials are suitable for intravitreal or periocular administration and can provide prolonged drug delivery and therapeutic benefits to patients to which the materials have been administered. The alpha 2 adrenergic receptor agonists can be provided in liquid-containing formulations and/or bioerodible and/or non-bioerodible polymeric implants and microparticles. Methods of making and using the present materials are also described.

Claims

1. An ophthalmically therapeutic material, comprising:

a therapeutic component comprising a therapeutically effective amount of an alpha 2 adrenergic receptor agonist having a structure effective in providing elimination of the agonist from the anterior chamber of an eye to which the agonist is administered.

2. The material of claim 1, further comprising a liquid carrier component associated with the therapeutic component in the form of a composition suitable for administration to a patient by at least one of intravitreal administration and periocular administration.

3. The material of claim 1, further comprising a polymeric component associated with the therapeutic component in the form of a polymeric drug delivery system suitable for administration to a patient by at least one of intravitreal administration and periocular administration.

4. The material of claim 3, wherein the polymeric drug delivery system is selected from the group consisting of biodegradable polymeric implants, non-biodegradable polymeric implants, biodegradable polymeric microparticles, and combinations thereof.

5. The material of claim 3, wherein the polymeric component comprises a poly (lactide-co-glycolide) polymer.

6. The material of claim 3, wherein the polymeric component comprises a polymer selected from the group consisting of poly-lactic acid (PLA), poly-glycolic acid (PGA), poly-lactide-co-glycolide (PLGA), polyesters, poly(ortho ester), poly(phosphazine), poly(phosphate ester), polycaprolactones, gelatin, collagen, derivatives thereof, and combinations thereof.

7. The system of claim 3, wherein the therapeutic component and the polymeric component are associated in the form of an implant selected from the group consisting of solid implants, semisolid implants, and viscoelastic implants.

8. The material of claim 1, wherein the alpha 2 adrenergic receptor agonist is provided in an amount to provide a therapeutic effect selected from the group consisting of neuroprotection, reduction in intraocular pressure, and combinations thereof.

9. The material of claim 1, wherein the alpha 2 adrenergic receptor agonist has an intravitreal half life after solution dosing greater than about three hours.

10. The material of claim 1, wherein the alpha 2 adrenergic receptor agonist is associated with a bulking agent.

11. The material of claim 1, wherein the alpha 2 adrenergic receptor agonist is coupled to a polyethylene glycol.

12. The material of claim 1, wherein the alpha 2 adrenergic receptor agonist has a molecular weight greater than the molecular weight of a different alpha 2 adrenergic receptor agonist that is eliminated from the posterior segment of an eye of an individual.

13. The material of claim 1, wherein the alpha 2 adrenergic receptor agonist has a structure effective in providing substantially equal elimination rates from the anterior chamber of the eye and the posterior segment of the eye.

14. The material of claim 1, wherein the alpha 2 adrenergic receptor agonist has a structure effective in providing a greater enhanced anterior elimination rate relative to a posterior elimination rate.

15. The material of claim 1, wherein the material is suitable for administration to an eye and delivers the alpha 2 adrenergic receptor agonist to a region of the eye selected from the group consisting of the anterior chamber of the eye, the posterior chamber of the eye, or combinations thereof.

16. The material of claim 1, further comprising an excipient component.

17. The material of claim 1, wherein the therapeutic component is produced by a process comprising selecting an alpha 2 adrenergic receptor agonist that has a vitreous half-life greater than about 3 hours.

18. The material of claim 1, wherein the alpha 2 adrenergic receptor agonist is an organic cation having a pKa less than about 7.

19. The material of claim 1, wherein the alpha 2 adrenergic receptor agonist is a non-cationic agent in the interior of an eye.

25. A method of improving or maintaining vision of an eye of a patient, comprising the step of administering the material of claim 1 to an eye of an individual.

26. The method of claim 25, wherein the method is effective to treat an ocular condition selected from the group consisting of anterior ocular conditions, posterior ocular conditions, and combinations thereof.

27. The method of claim 25, wherein the method is effective to provide neuroprotection to ocular neuronal cells and to reduce elevated intraocular pressure.

28. The method of claim 25, wherein the method is effective in treating glaucoma.

29. The method of claim 25, wherein the material is administered by a step selected from the group consisting of intraocular administration, periocular administration, and combinations thereof.

30. The method of claim 25, wherein the material is administered by intravitreal injection of the material into the eye.

31. The method of claim 25, wherein the administering comprises subconjunctival administration or periocular administration to deliver the alpha 2 adrenergic receptor agonist to a posterior structure of the eye selected from the group consisting of:

the uveal tract, the vitreous, the retina, the choroid, the retinal pigment epithelium, and combinations thereof.

32. The method of claim 25, wherein the administering comprises administering the material to a location in the eye selected from the group consisting of the anterior chamber, the posterior chamber, and combinations thereof.

33. The method of claim 25, wherein the administering comprises using a syringe or a trocar to administer the material to the eye.

20. A method of producing an ophthalmically therapeutic material, comprising:

selecting an alpha 2 adrenergic receptor agonist that has a vitreous half-life greater than about 3 hours; and

combining the selected alpha 2 adrenergic receptor agonist with a liquid carrier component or a polymeric component to form a material suitable for administration to an eye.

21. The method of claim 20, wherein further comprising at least one step selected from the group consisting of:

administering an alpha 2 adrenergic receptor agonist to an eye of a subject and determining the concentration of the alpha 2 adrenergic receptor agonist in at least one of the vitreous humor and aqueous humor as a function of time; and

administering an alpha 2 adrenergic receptor agonist to an eye of a subject and determining at least one of the vitreous half-life and clearance of the alpha 2 adrenergic receptor agonist from the eye.

22. The method of claim 20, wherein the material is selected from the group consisting of a liquid-containing composition, biodegradable polymeric implants, non-biodegradable polymeric implants, and polymeric microparticles.

23. The method of claim 20, wherein the material is selected from the group consisting of solid implants, semisolid implants, and viscoelastic implants.

24. The method of claim 20, wherein the alpha 2 adrenergic receptor agonist is combined with a polymeric component to form a mixture, and the method further comprises extruding the mixture.