DRUG DELIVERY TO THE ANTERIOR AND POSTERIOR SEGMENTS OF THE EYE USING EYE DROPS

• US 20110104155A1
• Filed: 05/05/2008
• Published: 05/05/2011
• Est. Priority Date: 03/11/2008
• Status: Abandoned Application

• Current Assignee: Raouf Rekik
• Original Assignee: Raouf Rekik
• Inventors: Rekik, Raouf
• Application Number:
  US12/921,958
• Publication Number:
  US 20110104155A1
• Time in Patent Office: Days
• US Class Current: 424/133.1
• 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 31/137 Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
• CPC Class Codes: A61K 31/403 condensed with carbocyclic rings, e.g. carbazole
• CPC Class Codes: A61K 31/415 1,2-Diazoles
• CPC Class Codes: A61K 31/4168 having a nitrogen attached in position 2, e.g. clonidine
• 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 31/502 ortho- or peri-condensed with carbocyclic ring systems, e.g. cinnoline, phthalazine
• CPC Class Codes: A61K 31/5377 not condensed and containing further heterocyclic rings, e.g. timolol
• CPC Class Codes: A61K 39/3955 against proteinaceous materials, e.g. enzymes, hormones, lymphokines
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/0048 Eye, e.g. artificial tears
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 27/10 for accommodation disorders, e.g. myopia
• 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: C07K 16/22 against growth factors ; against growth regulators

Abstract

A method and means for delivery of drugs to the chorio-retina and the optic nerve head which comprises contacting the surface of the eye with an effective amount of drug for treatment of chorio-retina and optic nerve head and a physiologically acceptable adrenergic agent for enhancing delivery of the drug to these tissues in an ophtalmologically acceptable carrier, said adrenergic agent being selected from the group consisting of alpha adrenergic agonist agents, derivatives of the alpha adrenergic agonist agents, beta-blocking agents, derivatives of the beta-blocking agents and mixtures thereof.

Claims

1. A method for delivering drugs to the posterior and anterior segments of the eyes comprising:

contacting the surface of the eye with an effective amount of a drug for treating eye disorders and/or diseases of the eye and a physiologically acceptable amount of a an adrenergic agent selected from the group consisting of alpha adrenergic agonist agents, derivatives of the alpha adrenergic agonist agents, beta-blocking agents, derivatives of the beta-blocking agents and mixtures thereof, in an opthamologically acceptable carrier.

2. The method according to claim 1, wherein the drugs are delivered to the posterior segment of the eye.

3. The method according to claim 2, wherein said drug for treating eye disorders and/or diseases of the eye and said adrenergic agent are delivered to the chorio-retina and optic nerve head of the eyes.

4. The method according to any one of claims 1 to 3, wherein the alpha adrenergic agonist agent(s) or derivative(s) thereof contacts the eye prior to said effective amount of said drug for treating eye disorders and/or diseases of the eye.

5. The method according to any one of claims 1 to 3, wherein the beta-blocking agent(s) or derivative(s) thereof contacts the eye prior to the effective amount of said drug for treating eye disorders and/or diseases of the eye.

6. The method according to any one of claims 1 to 3, wherein the alpha adrenergic agonist agent(s) or derivative(s) thereof and the beta-blocking agent(s) or derivative(s) thereof contacts the eye prior to said effective amount of said drug for treating eye disorders and/or diseases of the eye.

7. The method according to any one of claims 1 to 6, wherein the alpha adrenergic agonist agent is selected from the group of neosynephrine, beta-methylepinephrine, brimonidine, apraclonidine, clonidine, guanfacine, guanabenz, tizandine and mixtures thereof.

8. The method according to any one of claims 1 to 7, wherein the beta-blocking agent is selected from the group of timolol, sotalol, propanolol, nadolol, metoprolol, labetalol, esmolol, carteolol, betaxolol, bisoprolol, acebutolol, levobunolol, metipranolol and mixtures thereof.

9. The method according to any one of claims 1 to 8, wherein the drug for treating eye disorders and/or diseases of the eye is selected from the group comprising neuroprotective agents, growth factor vasoactive agents, calcium antagonists, angiotensin converting enzyme inhibitors, nitrates or nitric oxide generators, beta adrenergic agonists, antioxidants and radical scavengers, dopaminergic and serotoninergic agents, monoamine oxidase inhibitors, anti-inflammatory agents, growth factors, neuropeptides, anti-inflammatory mediators, anti-infective agents, anti-ischemic association agents, non-steroidal anti-inflammatory agents, anti-growth factor agents, and mixtures thereof.

10. The method according to claim 9, wherein said anti-growth factor agents are selected from the group consisting of anti-platelet derived growth factor (anti-PDGF) agents, anti-fibroblast growth factor (anti-FGF) agents, anti-placenta growth factor agents, anti-insulin like growth factor (anti-IGF) agents and anti-vascular endothelial growth factor (anti-VEGF) agents and mixtures thereof.

11. The method according to claim 9 or 10, wherein said anti-VEGF agents are selected from the group comprising bevacizumab (Avastin®

), ranibizumab (Iucentis®

), pegaptanib (Macugen®

) and mixtures thereof.

12. The method according to claim 9, wherein said anti-inflammatory agents are selected from the group comprising non-steroidal anti-inflammatory agents, corticosteroids, and mixtures thereof.

13. The method according to claim 9, wherein said anti-infective agents are selected from the group comprising antibiotics, antifungal agents, antiviral agents and mixtures thereof.

15. The method according to any one of claims 1 to 14, wherein said disease of the eye is selected from the group comprising or consisting of glaucomatous neuropathy, diabetic retinopathy, retinal vein occlusion, in particular central retinal vein occlusion or branch retinal vein occlusion, macular choroidal neovascularization, uveitis, optic nerve head inflammation, central arterial occlusion, central serous chorio retinopathy (CSCR), presbyopia, dry and exsudative macular degeneration, age related macular degeneration or high myopia macular degeneration, papillitis, endophthalmitis and pigmentosa retinopathy.

16. The method according to claim 15, wherein said macular choroidal neovasculation is due to age related macular degeneration or high myopia.

17. The method according to claim 15, wherein said uveitis is anterior and/or posterior uveitis.

18. The method according to any one of claims 1 to 17, for improving vision of eyes.

19. The method according to claim 18, wherein distance vision and/or near vision is improved.

20. The method according to any one of claims 1 to 19, to perform topic anaesthesia as a prelude to surgery.

21. The method according to any one of claims 1 to 20, wherein the drug for treatment of eye disorders and/or diseases of the eye is administered topically.

14. A method of treating a eye disorders and/or diseases of the eye by delivering drugs to the chorio-retina and optic nerve head of an eye comprising administering to a person or an animal in need of such treatment an effective amount of a drug for treatment of the chorio-retina and optic nerve head and a physiologically acceptable amount of an adrenergic agent selected from the group consisting of alpha adrenergic agonist agents, derivatives of the alpha adrenergic agonist agents, beta-blocking agents, derivatives of the beta-blocking agents and mixtures thereof.

22. A composition comprising, consisting essentially or consisting of:

a) an adrenergic agent selected from the group consisting of alpha adrenergic agonist agents, derivatives of the alpha adrenergic agonist agents, beta-blocking agents, derivatives of the beta-blocking agents and mixtures thereof, and

b) a drug for treating eye disorders and/or diseases of the eye.

23. The composition according to claim 22, wherein said drug for treating eye disorders and/or diseases of the eye is selected from the group comprising neuroprotective agents, growth factor vasoactive agents, calcium antagonists, angiotensin converting enzyme inhibitors, nitrates or nitric oxide generators, beta adrenergic agonists, antioxidants and radical scavengers, dopaminergic and serotoninergic agents, monoamine oxidase inhibitors, anti-inflammatory agents, growth factors, neuropeptides, anti-inflammatory mediators, anti-infective agents, anti-ischemic association agents, non-steroidal anti-inflammatory agents, anti-growth factor agents, and mixtures thereof.

24. The composition according to claim 22 or 23, wherein said drug for treating eye disorders and/or diseases of the eye is selected from the group consisting of angiotensin converting enzyme inhibitors, non-steroidal anti-inflammatory agents, anti-growth factor agents, corticosteroids, and mixtures thereof.

25. The composition according to according to any one of claims 22 to 24, wherein

a) the adrenergic agent is an alpha adrenergic agonist agent, a derivative or derivatives thereof or mixtures thereof, and

b) the drug for treating eye disorders and/or diseases of the eye is an angiotensin converting enzyme inhibitor and/or a non-steroidal inflammatory agent (anti-ischemic complex).

26. The composition according to any one of claims 22 to 25, for the topical treatment of eye disorders and/or diseases of the eye selected from the group of glaucomatous neuropathy, central serous chorio retinopathy, high myopia chorio-retinopathy, pigmentosa retinopathy, diabetic retinopathy, retinal vein occlusion, in particular central retinal vein occlusion or branch retinal vein occlusion, presbyopia, age related vision degradation, central retinal artery occlusion, dry and exsudative macular degeneration (age related macular degeneration, high myopia), uveitis, papillitis, endophthalmitis and macular oedema.

27. The composition according to claim 26, wherein the eye disorders and/or diseases of the eye comprises at least one eye disorder and/or disease of the eye.

28. The composition according to claim 26, wherein said dry or exsudative macular degeneration is age related macular degeneration or high myopia macular degeneration.

32. A composition according to any one of claims 22 to 32, wherein said agents and/or factors are delivered to the posterior segment of the eye.

29. A composition for the topical treatment of diabetic retinopathy, macular oedema, central retinal vein occlusion, branch retinal vein occlusion, exsudative macular degeneration (age related macular degeneration, high myopia macular degeneration), uveitis, papillitis, and endophthalmitis comprising, consisting or consisting essentially of

a) an adrenergic agent selected from the group consisting of alpha adrenergic agonist agents, derivatives of the alpha adrenergic agonist agents, beta-blocking agents, derivatives of the beta-blocking agents and mixtures thereof, and

b) an anti-vascular endothelial growth factor agent (anti-VEGF agents), a corticosteroid, a non steroidal anti-inflammatory agent or mixtures thereof.

30. A composition for the topical treatment of diabetic retinopathy macular oedema, exsudative macular degeneration, central retinal vein occlusion or branch retinal vein occlusion, uveitis, papillitis, or endophtalmitis comprising, consisting or consisting essentially of

a) an adrenergic agent selected from the group consisting of alpha adrenergic agonist agents, derivatives of the alpha adrenergic agonist agents, beta-blocking agents, derivatives of the beta-blocking agents and mixtures thereof, and

b) angiotensin converting enzyme inhibitor(s) and/or non steroidal anti-inflammatory agent(s) and/or corticosteroid(s), or mixtures thereof.

31. A composition for the topical treatment of age related vision degradation and presbyopia comprising, consisting or consisting essentially of

a) an alpha adrenergic agonist agent and/or a derivative of an alpha adrenergic agonist agent and

b) an angiotensin converting enzyme inhibitor and/or a non steroidal anti-inflammatory agent and/or an anti vascular endothelial growth factor agent selected from the group comprising bevacizumab (Avastin®

), ranibizumab (Iucentis®

), pegaptanib (Macugen®

) and mixtures thereof.

33. A method for increasing the transfer of a drug into the eye orbit, the posterior sclera and then into chorio-retina and optic nerve head to treat disorders and/or diseases of the eye comprising contacting the surface of an eye or both eyes with a physiologically acceptable adrenergic agent selected from the group consisting of alpha adrenergic agonist agents, derivatives of the alpha adrenergic agonist agents, beta-blocking agents, derivatives of the beta-blocking agents and mixtures thereof, and a pharmaceutically acceptable amount of a second drug that treats disorders and/or diseases of the eyes.

34. An adrenergic agent for the transfer, to the posterior segment of one or both eye(s), of a second drug that treats disorders and/or diseases of the eyes, to treat diseases and/or disorders of the eye, wherein said adrenergic agent is selected from the group consisting of alpha adrenergic agonist agents, derivatives of the alpha adrenergic agonist agents, beta-blocking agents, derivatives of the beta-blocking agents and mixtures thereof.

35. The adrenergic agent according to claim 34, wherein said adrenergic agent and said second drug are delivered to the chorio-retina and optic nerve head.

36. The adrenergic agent according to claim 34 or claim 35, wherein said alpha adrenergic agonist agent is selected from the group consisting of neosynephrine, beta-methylepinephrine, brimonidine, apraclonidine, clonidine, guanfacine, guanabenz, tizandine and mixtures thereof.

37. The adrenergic agent according to any one of claims 34 to 36, wherein the beta-blocking agent is selected from the group of timolol, sotalol, propanolol, nadolol, metoprolol, labetalol, esmolol, carteolo, betaxolol, bisoprolol, acebutolol, levobunolol, metipranolol and mixtures thereof.

38. The adrenergic agent according to any one of claims 34 to 37, wherein the drug for treating eye disorders and/or diseases of the eye is selected from the group comprising neuroprotective agents, growth factor vasoactive agents, calcium antagonists, angiotensin converting enzyme inhibitors, nitric oxide generators, agents for the treatment of vascular disease, antioxidants, radical scavengers, anti-inflammatory agents, anti-infective agents, anti-growth factor agents and mixtures thereof.

39. The adrenergic agent according to claim 38, wherein said anti-growth factor agents are selected from the group consisting of anti-platelet derived growth factor (anti-PDGF) agents, anti-fibroblast growth factor (anti-FGF) agents, anti-placenta growth factor agents, anti-insulin like growth factor agents and anti-vascular endothelial growth factor (anti-VEGF) agents and mixtures thereof.

40. The adrenergic agent according to claim 39, wherein said anti-VEGF agent is selected from the group consisting of bevacizumab (Avastin®

), ranibizumab (Iucentis®

), pegaptanib (Macugen®

) and mixtures thereof.

41. The adrenergic agent according to claim 38, wherein said anti-inflammatory agents are selected from the group comprising corticosteroids, non-steroidal inflammatory agents, and mixtures thereof.

42. The adrenergic agent according to claim 38, wherein said anti-infective agents are selected from the group comprising antibiotics, antifungal agents, antiviral agents and mixtures thereof.

43. A kit comprising, consisting or consisting essentially of

a) an adrenergic agent selected from the group consisting of alpha adrenergic agonist agents, derivatives of the alpha adrenergic agonist agents, beta-blocking agents, derivatives of the beta-blocking agents and mixtures thereof;

and

b) a drug for treating eye disorders and/or diseases of the eye.

45. The kit according to claim 43 or 44, wherein said drug for treating eye disorders and/or diseases of the eye is selected from the group comprising neuroprotective agents, growth factor vasoactive agents, calcium antagonists, angiotensin converting enzyme inhibitors, nitrates or nitric oxide generators, beta adrenergic agonists, antioxidants and radical scavengers, dopaminergic and serotoninergic agents, monoamine oxidase inhibitors, anti-inflammatory agents, growth factors, neuropeptides, anti-inflammatory mediators, anti-infective agents, anti-ischemic association agents, non-steroidal anti-inflammatory agents, anti-growth factor agents, and mixtures thereof.

46. The kit according to an one of claims 43 to 45, wherein said drug for treating eye disorders and/or diseases of the eye is selected from the group consisting of angiotensin converting enzyme inhibitors, non-steroidal anti-inflammatory agents, anti-growth factor agents, steroidal anti-inflammatory agents, in particular corticosteroids, and mixtures thereof.

47. The kit according to an one of claims 43 to 46, wherein

a) said adrenergic agent is an alpha adrenergic agonist agent and/or a derivative or derivative(s) thereof, and

b) said drug for treating eye disorders and/or diseases of the eye is an angiotensin converting enzyme inhibitor and/or a non-steroidal anti-inflammatory agent (anti-ischemic complex).

48. The kit according to any one of claims 43 to 46, wherein said drug for treating eye disorders and/or diseases of the eye is selected from the group consisting of:

anti-VEGF agents, in particular bevacizumab (Avastin®

), ranibizumab (Iucentis®

), pegaptanib (Macugen®

) and mixtures thereof;

angiotensin converting enzyme inhibitors,

a non-steroidal anti-inflammatory agent, and

mixture thereof.

49. The kit according to any one of claims 43 to 46, wherein said drug for treating eye disorders and/or diseases of the eye is selected from the group consisting of:

corticosteroids,

angiotensin converting enzyme inhibitors,

a non-steroidal anti-inflammatory agent, and

mixture thereof.

50. The kit according to any one of claims 43 to 46, wherein said drug for treating eye disorders and/or diseases of the eye is an anti-growth factor agents selected from the group consisting of anti-platelet growth factor (anti-PDGF) agents, anti-fibroblast growth factor (anti-FGF) agents, anti-placenta growth factor agents, anti-insulin like growth factor agents and anti-vascular endothelial growth factor (anti-VEGF) agents and mixtures thereof.

44. A kit comprising, consisting or consisting essentially of

a) a composition comprising or consisting of an adrenergic agent selected from the group consisting of alpha adrenergic agonist agents, derivatives of the alpha adrenergic agonist agents, beta-blocking agents, derivatives of the beta-blocking agents and mixtures thereof;

and

b) a drug for treating eye disorders and/or diseases of the eye.

51. Use of an adrenergic agent and a pharmaceutically acceptable amount of a second drug that treats disorders and/or diseases of the eyes a drug for the manufacture of a medicament to treat disorders and/or diseases of the eye, wherein said adrenergic agent is selected from the group consisting of alpha adrenergic agonist agents, derivatives of the alpha adrenergic agonist agents, beta-blocking agents, derivatives of the beta-blocking agents and mixtures thereof.