USRE47045EActiveUtility

Compositions and methods for treating macular degeneration

74
Assignee: UNIV COLUMBIAPriority: Sep 12, 2007Filed: Sep 12, 2008Granted: Sep 18, 2018
Est. expirySep 12, 2027(~1.1 yrs left)· nominal 20-yr term from priority
Inventors:Ilyas Washington
A61P 27/02A61K 31/135A61K 31/167A61K 31/215A61K 45/06A23V 2002/00A61K 31/203A23L 33/10A61K 9/0048
74
PatentIndex Score
3
Cited by
132
References
54
Claims

Abstract

Methods of retarding formation of a lipofuscin pigment in the retina and of treating or ameliorating the effects of a disease characterized by an accumulation of a lipofuscin pigment in a retina are provided. These methods include the step of administering to a patient in need thereof a substituted C 20 -retinoid in an amount sufficient to reduce accumulation of a lipofuscin pigment in the retina. Further provided are methods of retarding formation of A2E and/or ATR-dimer by replacing an all-frans-retinal (ATR) substrate with a C 20 -D 3 -retinal substrate under conditions sufficient to impede the formation of A2E. Compositions for retarding formation of a lipofuscin pigment in the retina containing a substituted C 20 -retinoid and a pharmaceutically acceptable carrier are also provided.

Claims

exact text as granted — not AI-modified
What is claimed is: 
     
       1. A method of retarding the accumulation of a lipofuscin pigment in a retina, comprising administering an effective amount of a pharmaceutical composition to a patient in need thereof, wherein the pharmaceutical composition comprises a substituted C 20 -D 1-3 -retinoid, wherein the C 20 -D 1-3 -retinoid is selected from the group consisting of C 20 -D 1-3 -retinol, C 20 -D 1-3 -retinol ester, C 20 -D 1-3 -retinal, and C 20 -D 1-3 -pro-vitamin A carotenoids, and a pharmaceutically acceptable carrier. 
     
     
       2. The method according to  claim 1 , wherein the substituted C 20 -D 1-3 -retinoid is a C 20 -D 3 -retinoid. 
     
     
       3. The method according to  claim 1 , wherein the pharmaceutical composition is suitable for use as a nutraceutical composition. 
     
     
       4. The method according to  claim 1 , wherein the patient is in need of treatment for a macular degeneration. 
     
     
       5. The method according to  claim 4 , wherein the macular degeneration is age-related macular degeneration. 
     
     
       6. The method according to  claim 5 , wherein the C 20 -D 1-3 -retinoid is C 20 -D 1-3 -retinol or a C 20 -D 1-3 -retinol ester. 
     
     
       7. The method according to  claim 5 , wherein the C 20 -D 1-3 -retinoid is C 20 -D 3 -retinol, a C 20 -D 3 -retinol ester, C 20 -D 3 -retinal, or a C 20 -D 3 -pro-vitamin A carotenoid. 
     
     
       8. The method according to  claim 5 , wherein the C 20 -D 1-3 -retinoid is C 20 -D 3 -retinol acetate. 
     
     
       9. The method according to  claim 8 , wherein the C 20 -D 3 -retinal, corresponding to the aldehyde of the C 20 -D 3 -retinol acetate, forms A2E in vitro about 7 times slower than non-deuterium-enriched retinal retinol acetate. 
     
     
       10. The method according to  claim 5 , wherein the patient is in need of treatment for dry (non-neovascular) age-related macular degeneration. 
     
     
       11. The method according to  claim 1 , wherein the patient is in need of treatment for Stargardt disease. 
     
     
       12. The method according to  claim 11 , wherein the C 20 -D 1-3 -retinoid is C 20 -D 1-3 -retinol or a C 20 -D 1-3 -retinol ester. 
     
     
       13. The method according to  claim 11 , wherein the C 20 -D 1-3 -retinoid is C 20 -D 3 -retinol, a C 20 -D 3 -retinol ester, C 20 -D 3 -retinal, or a C 20 -D 3 -pro-vitamin A-carotenoid. 
     
     
       14. The method according to  claim 11 , wherein the C 20 -D 1-3 -retinoid is C 20 -D 3 -retinol acetate. 
     
     
       15. The method according to  claim 14 , wherein the C 20 -D 3 -retinal, corresponding to the aldehyde of the C 20 -D 3 -retinol acetate, forms A2E in vitro about 7 times slower than non-deuterium-enriched retinal retinol acetate. 
     
     
       16. The method according to  claim 1 , wherein the patient is in need of treatment for a macular degeneration selected from the group consisting of Vitelliform or Best disease, Sorsby's fundus dystrophy, retinitis pigmentosa, and Malattia Leventinese. 
     
     
       17. The method according to  claim 16 , wherein the C 20 -D 1-3 -retinoid is C 2 O-D 3 -retinol C 20 -D 3 -retinol acetate. 
     
     
       18. The method according to  claim 1 , wherein the patient is in need of treatment for a macular degeneration characterized by one or more mutation(s) in the ABCA4 gene. 
     
     
       19. The method according to  claim 1 , wherein the substituted C 20 -D 1-3 -retinoid is present in the pharmaceutical composition at a level sufficient to deliver on average about 0.1 to about 90 mg/day to a patient. 
     
     
       20. The method according to  claim 1 , further comprising an additional active. 
     
     
       21. The method according to  claim 20 , wherein the additional active is selected from the group consisting of eye antioxidants, minerals, negatively-charged phospholipids, carotenoids, and combinations thereof. 
     
     
       22. The method according to  claim 21 , wherein the eye antioxidant is selected from the group consisting of vitamin C, vitamin E, beta-carotene, coenzyme Q, OT-551, 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl, butylated hydroxytoluene, resveratrol, a trolox analogue (PNU-83836-E), bilberry extract, and combinations thereof. 
     
     
       23. The method according to  claim 21 , wherein the mineral is selected from the group consisting of cupric oxide, zinc oxide; selenium-containing compounds, and combinations thereof. 
     
     
       24. The method according to  claim 21 , wherein the negatively charged phospholipid is selected from the group consisting of cardiolipin, phosphatidylglycerol, and combinations thereof. 
     
     
       25. The method according to  claim 21 , wherein the carotenoid is selected from the group consisting of zeaxanthin, lutein, and combinations thereof. 
     
     
       26. The method according to claim  1  2, wherein the C 20 -D 3 -retinal, corresponding to the aldehyde of the C 20 -D 3 -retinol acetate, C 20 -D 1-3 -retinoid forms A2E in vitro about 7 times slower than non-deuterium-enriched retinal the corresponding non-deuterated retinoid. 
     
     
       27. The method according to claim  1  2, wherein the pharmaceutical composition is administered directly to the eye. 
     
     
       28. A method of treating a macular degeneration, comprising administering an effective amount of a substituted C 20 -D 1-3 -retinoid to a patient in need thereof, wherein the substituted C 20 -D 1-3 -retinoid is selected from the group consisting of C 20 -D 1-3 -retinol, C 20 -D 1-3 -retinol ester, C 20 -D 1-3 -retinal and C 20 -D 1-3 -pro-vitamin A carotenoids.  
     
     
       29. A method of treating a macular degeneration, comprising administering an effective amount of a pharmaceutical composition to a patient in need thereof, wherein the pharmaceutical composition comprises a substituted C 20 -D 1-3 -retinoid, wherein the C 20 -D 1-3 -retinoid is selected from the group consisting of C 20 -D 1-3 -retinol, C 20 -D 1-3 -retinol ester, C 20 -D 1-3 -retinal and C 20 -D 1-3 -pro-vitamin A carotenoids, and a pharmaceutically acceptable carrier.  
     
     
       30. The method according to claim 29, wherein the substituted C 20 -D 1-3 -retinoid is a C 20 -D 3 -retinoid.  
     
     
       31. The method according to claim 29, wherein the pharmaceutical composition is suitable for use as a nutraceutical composition.  
     
     
       32. The method according to claim 29, wherein the macular degeneration is age-related macular degeneration.  
     
     
       33. The method according to claim 32, wherein the C 20 -D 1-3 -retinoid is C 20 -D 1-3 -retinol or a C 20 -D 1-3 -retinol ester.  
     
     
       34. The method according to claim 32, wherein the C 20 -D 1-3 -retinoid is C 20 -D 3 -retinol, a C 20 -D 3 -retinol ester, C 20 -D 3 -retinal, or a C 20 -D 3 -pro-vitamin A carotenoid.  
     
     
       35. The method according to claim 32, wherein the C 20 -D 1-3 -retinoid is C 20 -D 3 -retinol acetate.  
     
     
       36. The method according to claim 35, wherein the C 20 -D 3 -retinol acetate forms A2E about 7 times slower than non-deuterium-enriched retinol acetate.  
     
     
       37. The method according to claim 32, wherein the patient is in need of treatment for dry (non-neovascular) age-related macular degeneration.  
     
     
       38. The method according to claim 29, wherein the macular degeneration is Stargardt disease.  
     
     
       39. The method according to claim 38, wherein the C 20 -D 1-3 -retinoid is C 20 -D 1-3 -retinol or a C 20 -D 1-3 -retinol ester.  
     
     
       40. The method according to claim 38, wherein the C 20 -D 1-3 -retinoid is C 20 -D 3 -retinol, a C 20 -D 3 -retinol ester, C 20 -D 3 -retinal, or a C 20 -D 3 -pro-vitamin A-carotenoid.  
     
     
       41. The method according to claim 38, wherein the C 20 -D 1-3 -retinoid is C 20 -D 3 -retinol acetate.  
     
     
       42. The method according to claim 41, wherein the C 20 -D 3 -retinol acetate forms A2E about 7 times slower than non-deuterium-enriched retinal acetate.  
     
     
       43. The method according to claim 29, wherein the macular degeneration is selected from the group consisting of Vitelliform or Best disease, Sorsby's fundus dystrophy, retinitis pigmentosa, and Malattia Leventinese.  
     
     
       44. The method according to claim 43, wherein the C 20 -D 1-3 -retinoid is C 20 -D 3 -retinol acetate.  
     
     
       45. The method according to claim 29, wherein the macular degeneration is characterized by one or more mutation(s) in the ABCA4 gene.  
     
     
       46. The method according to claim 29, wherein the substituted C 20 -D 1-3 -retinoid is present in the pharmaceutical composition at a level sufficient to deliver on average about 0.1 to about 90 mg/day to a patient.  
     
     
       47. The method according to claim 29, further comprising an additional active.  
     
     
       48. The method according to claim 47, wherein the additional active is selected from the group consisting of eye antioxidants, minerals, negatively-charged phospholipids, carotenoids, and combinations thereof.  
     
     
       49. The method according to claim 47, wherein the eye antioxidant is selected from the group consisting of vitamin C, vitamin E, beta-carotene, coenzyme Q, OT-551, 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl, butylated hydroxytoluene, resveratrol, a trolox analogue (PNU-83836-E), bilberry extract, and combinations thereof.  
     
     
       50. The method according to claim 47, wherein the mineral is selected from the group consisting of cupric oxide, zinc oxide, selenium-containing compounds, and combinations thereof.  
     
     
       51. The method according to claim 47, wherein the negatively charged phospholipid is selected from the group consisting of cardiolipin, phosphatidylglycerol, and combinations thereof.  
     
     
       52. The method according to claim 47, wherein the carotenoid is selected from the group consisting of zeaxanthin, lutein, and combinations thereof.  
     
     
       53. The method according to claim 29, wherein the C 20 -D 1-3 -retinoid forms A2E about 7 times slower than non-deuterium enriched retinoid.  
     
     
       54. The method according to claim 29, wherein the pharmaceutical composition is administered directly to the eye.

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