Intraocular implants and methods for improving vision

• US 20050244476A1
• Filed: 04/29/2005
• Published: 11/03/2005
• Est. Priority Date: 04/30/2004
• Status: Active Grant

• Current Assignee: Allergan, Inc. (Canada) (Abbvie Incorporated)
• Original Assignee: Allergan, Inc. (Canada) (Abbvie Incorporated)
• Inventors: Jackson, Brittany A., Hughes, Patrick M., Wheeler, Larry A., Burke, James, Lin, Ton, Zhang, Kai-Ming, Donn, Rosy S., Huang, Glenn
• Granted Patent: US 8,293,741 B2
• Time in Patent Office: Days
• US Class Current: 424/427
• CPC Class Codes: A61K 31/498 Pyrazines or piperazines ortho- and peri-condensed with carbocyclic ring systems, e.g. quinoxaline, phenazine
• 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 9/0051 Ocular inserts, ocular implants
• CPC Class Codes: A61K 9/204 Polyesters, e.g. poly(lactide-co-glycolide)
• CPC Class Codes: A61L 2300/436 of receptors
• CPC Class Codes: A61L 2300/604 Biodegradation
• CPC Class Codes: A61L 27/58 Materials at least partially resorbable by the body
• CPC Class Codes: A61L 31/06 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds A61L31/041 takes precedence
• CPC Class Codes: A61L 31/148 Materials at least partially resorbable by the body
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 27/06 Antiglaucoma agents or miotics
• CPC Class Codes: A61P 27/16 Otologicals
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 31/18 for HIV
• CPC Class Codes: A61P 33/00 Antiparasitic agents
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C08L 67/04 Polyesters derived from hydroxycarboxylic acids, e.g. lactones C08L67/06 takes precedence
• CPC Class Codes: Y02A 50/30 : Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

Biocompatible intraocular implants include an alpha-2 adrenergic receptor agonist and a polymer associated with the alpha-2 adrenergic receptor agonist to facilitate release of the alpha-2 adrenergic receptor agonist into an eye for an extended period of time. The alpha-2 adrenergic receptor agonist may be associated with a biodegradable polymer matrix, such as a matrix of a two biodegradable polymers. The implants can be placed in an eye to treat one or more ocular conditions, such as an ocular vasculopathy or glaucoma, among others or to improve vision in a normal eye.

Claims

1. A biodegradable intraocular implant for improving vision, the implant comprising an alpha-2 adrenergic receptor agonist and a biodegradable polymer, the implant capable of releasing the alpha-2 adrenergic receptor agonist from the polymer, upon intravitreal placement of the implant, in an amount effective to improve the vision of the eye in which the implant is placed.

2. The implant of claim 1, wherein the alpha-2 adrenergic receptor agonist is selected from the group consisting of quinoxalines, (2-imidozolin-2-ylamino) quinoxalines, 5-bromo-6-(2-imidozolin-2-ylamino) quinoxalines, derivatives thereof and mixtures thereof.

3. The implant of claim 1, wherein the alpha-2 adrenergic receptor agonist is selected from the group consisting of brimonidine, salts thereof, and mixtures thereof.

4. The implant of claim 1, wherein the alpha-2 adrenergic receptor agonist is brimonidine tartrate.

5. The implant of claim 1, wherein the alpha-2 adrenergic receptor agonist is dispersed within the biodegradable polymer.

6. The implant of claim 1, wherein the biodegradable polymer comprises a mixture of a first biodegradable polymer of polylactic acid, and a different second biodegradable polymer of polylactic acid.

7. The implant of claim 1, wherein the polymer releases drug at a rate effective to sustain release of an amount of the alpha-2 adrenergic receptor agonist from the implant for more than one month from the time the implant is placed in the vitreous of the eye.

8. The implant of claim 1, wherein the polymer releases drug at a rate effective to sustain release of an amount of the alpha-2 adrenergic receptor agonist from the implant for more than forty days from the time the implant is placed in the vitreous of the eye.

9. The implant of claim 1, wherein the polymer releases drug at a rate effective to sustain release of an amount of the alpha-2 adrenergic receptor agonist from the implant for less than 35 days from the time the implant is placed in the vitreous of the eye.

10. A method of making a biodegradable intraocular implant, comprising the step of:

extruding a mixture of an alpha-2 adrenergic receptor agonist and a biodegradable polymer component to form a biodegradable material that releases drug at a rate effective to sustain release of an amount of the alpha-2 adrenergic receptor agonist from the implant for a time effective to improve vision in an eye in which the implant is placed.

11. The method of claim 10, wherein the alpha-2 adrenergic agonist is selected from the group consisting of quinoxalines, (2-imidozolin-2-ylamino) quinoxalines, 5-bromo-6-(2-imidozolin-2-ylamino) quinoxalines, derivatives thereof and mixtures thereof.

12. A method for improving or for maintaining vision, the method comprising the step of placing in the vitreous of an eye a biodegradable intraocular implant comprising an alpha-2 adrenergic receptor agonist associated with a biodegradable polymer, thereby improving or maintaining vision.

13. The method of claim 12, wherein the method is effective to treat an ocular condition selected from the group consisting of:

macular degeneration, macular edema, retinal arterial occlusive disease, central retinal vein occlusion, disseminated intravascular coagulopathy, branch retinal vein occlusion, hypertensive fundus changes, ocular ischemic syndrome, retinal arterial microaneurysms, hemi-retinal vein occlusion, central retinal artery occlusion, branch retinal artery occlusion, carotid artery disease (cad), eales disease, vasculopathies associated with diabetes, Non-Exudative Age Related Macular Degeneration, Exudative Age Related Macular Degeneration, Choroidal Neovascularization, Diabetic Retinopathy, Acute Macular Neuroretinopathy, Central Serous Chorioretinopathy, Cystoid Macular Edema, Diabetic Macular Edema, Acute Multifocal Placoid Pigment Epitheliopathy, Behcet'"'"'s Disease, Birdshot Retinochoroidopathy, Syphilis, Lyme, Tuberculosis, Toxoplasmosis, Intermediate Uveitis, Multifocal Choroiditis, Multiple Evanescent White Dot Syndrome, Ocular Sarcoidosis, Posterior Scleritis, Serpignous Choroiditis, Subretinal Fibrosis and Uveitis Syndrome, Vogt-Koyanagi-Harada Syndrome, Coat'"'"'s Disease, Parafoveal Telangiectasis, Papillophlebitis, Frosted Branch Angitis, Sickle Cell Retinopathy and other Hemoglobinopathies, Angioid Streaks, Familial Exudative Vitreoretinopathy, Sympathetic Ophthalmia, Uveitic Retinal Disease, Retinal Detachment, Trauma, Laser, photodynamic therapy, Photocoagulation, Hypoperfusion During Surgery, Radiation Retinopathy, Bone Marrow Transplant Retinopathy, Proliferative Vitreal Retinopathy and Epiretinal Membranes, Proliferative Diabetic Retinopathy, Ocular Histoplasmosis, Ocular Toxocariasis, Presumed Ocular Histoplasmosis Syndrome, Endophthalmitis, Toxoplasmosis, Retinal Diseases Associated with HIV Infection, Choroidal Disease Associated with HIV Infection, Uveitic Disease Associated with HIV Infection, Viral Retinitis, Acute Retinal Necrosis, Progressive Outer Retinal Necrosis, Fungal Retinal Diseases, Ocular Syphilis, Ocular Tuberculosis, Diffuse Unilateral Subacute Neuroretinitis, Myiasis, Retinitis Pigmentosa, Systemic Disorders with Associated Retinal Dystrophies, Congenital Stationary Night Blindness, Cone Dystrophies, Stargardt'"'"'s Disease and Fundus Flavimaculatus, Best'"'"'s Disease, Pattern Dystrophy of the Retinal Pigmented Epithelium, X-Linked Retinoschisis, Sorsby'"'"'s Fundus Dystrophy, Benign Concentric Maculopathy, Bietti'"'"'s Crystalline Dystrophy, pseudoxanthoma elasticum, Retinal Detachment, Macular Hole, Giant Retinal Tear, Retinal Disease Associated with Tumors, Congenital Hypertrophy of the RPE, Posterior Uveal Melanoma, Choroidal Hemangioma, Choroidal Osteoma, Choroidal Metastasis, Combined Hamartoma of the Retina and Retinal Pigmented Epithelium, Retinoblastoma, Vasoproliferative Tumors of the Ocular Fundus, Retinal Astrocytoma, Intraocular Lymphoid Tumors, Punctate Inner Choroidopathy, Acute Posterior Multifocal Placoid Pigment Epitheliopathy, Myopic Retinal Degeneration, and Acute Retinal Pigment Epithelitis.

14. The method of claim 12, wherein the alpha-2 adrenergic receptor agonist is selected from the group consisting of brimonidine, salts thereof, and mixtures thereof.

15. The method of claim 12, wherein the method can improve vision in a normal eye.

16. The method of claim 12, wherein the method can improve vision in a normal eye by up to about 56%.

17. The method of claim 12, wherein the method can improve vision in an eye with an ocular condition.

18. The method of claim 16, wherein the method can improve vision in an eye with an ocular condition by up to about 23%.

19. The method of claim 18, wherein the ocular condition is a vasculopathy.

20. The method of claim 18, wherein the ocular condition is due to an elevated intraocular pressure.

21. The method of claim 18, wherein the ocular condition is retinal ischemic injury.

22. The method of claim 12, wherein the implant releases the alpha-2 adrenergic receptor agonist from the polymer, upon intravitreal placement of the implant, for a period of about ninety days.

23. The method of claim 12, wherein the alpha-2 adrenergic receptor agonist is retained in the retina for a period of time longer than it is retained in the vitreous

24. A method for improving, maintaining, restoring or repairing vision, the method comprising the step of placing in the vitreous of an eye a biodegradable intraocular implant comprising a brimonidine associated with a biodegradable polymer, thereby improving, maintaining, restoring or repairing vision.