OCULAR THERAPY USING GLUCOCORTICOID DERIVATIVES SELECTIVELY PENETRATING POSTERIOR SEGMENT TISSUES

• US 20070088014A1
• Filed: 10/18/2006
• Published: 04/19/2007
• Est. Priority Date: 10/18/2005
• Status: Active Grant

• Current Assignee: Allergan Incorporated (Abbvie Incorporated)
• Original Assignee: Allergan Incorporated (Abbvie Incorporated)
• Inventors: Harrison, Kelly, Edelman, Jeffrey
• Granted Patent: US 8,062,657 B2
• Time in Patent Office: Days
• US Class Current: 514/179
• 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 31/728 Hyaluronic acid
• 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: A61K 9/0051 Ocular inserts, ocular implants
• CPC Class Codes: A61K 9/1647 Polyesters, e.g. poly(lactide-co-glycolide)
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 27/06 Antiglaucoma agents or miotics
• CPC Class Codes: A61P 27/14 Decongestants or antiallergics
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• 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: A61P 5/38 of the suprarenal hormones
• CPC Class Codes: A61P 5/44 Glucocorticosteroids; Drugs increasing or potentiating the activity of glucocorticosteroids
• CPC Class Codes: A61P 7/02 Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• 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

Ophthalmically therapeutic materials, such as liquid-containing compositions and polymeric drug delivery systems, include a therapeutic component that includes an Glucocorticoid Derivative which, upon delivery to the posterior segment of a mammalian eye, does not significantly diffuse to the anterior segment of said eye. Methods of making and using the present materials are also described.

Claims

1. An ophthalmic composition comprising:

a therapeutically effective amount of an Glucocorticoid Derivative (GD) having a structure effective to prevent diffusion of a biologically significant amount of the GD to the anterior chamber when the GD is administered to the posterior chamber of the eye.

2. ) The composition of claim 1 wherein said GD has a lipophilicity greater than 2.53.

3. ) The composition of claim 1 wherein said GD has a lipophilicity greater than about 3.5.

4. ) The composition of claim 1 wherein said GD has a lipophilicity greater than about 4.0.

5. ) The composition of claim 1 wherein said GD has a lipophilicity greater than about 4.2.

6. ) The composition of claim 1 wherein said GD has an aqueous solubility less than 10 mg/ml.

7. ) The composition of claim 1 wherein said GD has an aqueous solubility less than about 5 mg/ml.

8. ) The composition of claim 1 wherein said GD has an aqueous solubility less than about 2 mg/ml.

9. ) The composition of claim 1 wherein said GD has an aqueous solubility less than about 1 mg/ml.

10. ) The composition of claim 1 wherein said GD has an aqueous solubility less than about 0.5 mg/ml.

11. ) The composition of claim 1 wherein said GD has an aqueous solubility less than about 0.2 mg/ml.

12. ) The composition of claim 1 wherein said GD has an aqueous solubility less than about 0.14 mg/ml.

13. ) The composition of claim 1 wherein said GD comprises an acyl group linked to C₁₇ via an ester linkage.

14. ) The composition of claim 13 wherein said acyl group is selected from the group consisting of an acetyl, butyryl, valeryl, propionyl, furoyl, and benzoyl group.

15. ) The composition of claim 1 wherein said GD comprises an acyl group linked to C₂₁ via an ester linkage.

16. ) The composition of claim 15 wherein said acyl group is selected from the group consisting of an acetyl, butyryl, valeryl, propionyl, furoyl, and benzoyl group.

17. ) The composition of claim 1 wherein said GD comprises an acyl group linked to both C₁₇ and C₂₁ via an ester linkage.

18. ) The composition of claim 1 wherein said composition is suitable for administration to a patient by at least one of intravitreal administration and periocular administration.

19. ) The composition of claim 18, further comprising a polymeric component, said composition being in a form suitable for administration to a patient by at least one of intravitreal administration and periocular administration.

20. ) The composition of claim 19 wherein said polymeric component comprises a viscosity inducing component.

21. ) The composition of claim 20 wherein said polymeric component comprises hyaluronic acid.

22. ) The composition of claim 1 wherein said therapeutic component contains particles comprising a GD in solid form.

23. ) The composition of claim 20 wherein said therapeutic component contains particles comprising a GD in solid form.

24. ) The composition of claim 19 wherein said polymeric component is comprised in an implant containing the therapeutic component.

25. ) The composition of claim 24 wherein said polymeric component comprises a biodegradable polymer.

26. ) The composition of claim 25 wherein said polymeric component is selected from the group consisting of poly(lactide-co-glycolide) polymer (PLGA), poly-lactic acid (PLA), poly-glycolic acid (PGA), polyesters, poly(ortho ester), poly(phosphazine), poly(phosphate ester), polycaprolactones, gelatin, and collagen, and derivatives and combinations thereof.

27. ) A method of treating a condition of the posterior segment of a mammalian eye selected from the group consisting of macular edema, dry and wet macular degeneration, choroidal neovascularization, diabetic retinopathy, acute macular neuroretinopathy, central serous chorioretinopathy, cystoid macular edema, and diabetic macular edema, uveitis, retinitis, choroiditis, acute multifocal placoid pigment epitheliopathy, Behcet'"'"'s disease, birdshot retinochoroidopathy, syphilis, lyme, tuberculosis, toxoplasmosis, intermediate uveitis (pars planitis), multifocal choroiditis, multiple evanescent white dot syndrome (mewds), ocular sarcoidosis, posterior scleritis, serpiginous choroiditis, subretinal fibrosis and uveitis syndrome, Vogt-Koyanagi-and Harada syndrome;

retinal arterial occlusive disease, anterior uveitis, retinal vein occlusion, central retinal vein occlusion, disseminated intravascular coagulopathy, branch retinal vein occlusion, hypertensive fundus changes, ocular ischemic syndrome, retinal arterial microaneurysms, Coat'"'"'s disease, parafoveal telangiectasis, hemiretinal vein occlusion, papillophlebitis, central retinal artery occlusion, branch retinal artery occlusion, carotid artery disease (CAD), frosted branch angiitis, sickle cell retinopathy, angioid streaks, familial exudative vitreoretinopathy, and Eales disease;

traumatic/surgical conditions such as sympathetic ophthalmia, uveitic retinal disease, retinal detachment, trauma, photocoagulation, hypoperfusion during surgery, radiation retinopathy, and bone marrow transplant retinopathy;

proliferative vitreal retinopathy and epiretinal membranes, and proliferative diabetic retinopathy;

infectious disorders such as ocular histoplasmosis, ocular toxocariasis, presumed ocular histoplasmosis syndrome (POHS), endophthalmitis, toxoplasmosis, retinal diseases associated with HIV infection, choroidal disease associate with HIV infection, uveitic disease associate with HIV infection, viral retinitis, acute retinal necrosis, progressive outer retinal necrosis, fungal retinal diseases, ocular syphilis, ocular tuberculosis, diffuse unilateral subacute neuroretinitis, and myiasis;

genetic disorders such as 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, and pseudoxanthoma elasticum;

retinal tears/holes such as retinal detachment, macular hole, and giant retinal tear;

tumors such as retinal disease associated with tumors, congenital hypertrophy of the retinal pigmented epithelium, 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, and intraocular lymphoid tumors;

punctate inner choroidopathy, acute posterior multifocal placoid pigment epitheliopathy, myopic retinal degeneration, acute retinal pigement epitheliitis, retinitis pigmentosa, proliferative vitreal retinopathy (PVR), age-related macular degeneration (ARMD), diabetic retinopathy, diabetic macular edema, retinal detachment, retinal tear, uveitus, cytomegalovirus retinitis and glaucoma, comprising administering to the posterior segment of said eye a composition comprising a GD in an ophthalmically effective vehicle.

28. ) The method of claim 27 wherein said composition is administered intravitreally.

29. ) The method of claim 28 wherein said composition comprises a suspension of GD particles.

30. ) The method of claim 29 wherein said composition comprises a polymeric component.

31. ) The method of claim 30 wherein said polymeric component comprises hyaluronic acid.

32. ) The method of claim 31 wherein said pathological condition comprises macular edema.

33. ) The method of claim 32 wherein said pathological condition comprises macular degeneration.

34. ) The method of claim 28 wherein said composition comprises an intravitreal implant comprising a GD and a biocompatible polymer.

35. ) The method of claim 32 wherein said polymer is a biodegradable polymer.

36. ) The method of claim 35 wherein said biodegradable polymer is selected from the group consisting of poly(lactide-co-glycolide) polymer (PLGA), poly-lactic acid (PLA), poly-glycolic acid (PGA), polyesters, poly(ortho ester), poly(phosphazine), poly(phosphate ester), polycaprolactones, gelatin, and collagen, and derivatives and combinations thereof.