Methods for inhibition of angiogenesis with a composition comprising 3-hydroxythalidomide

Abstract

The present invention comprises a group of compounds that effectively inhibit angiogenesis. More specifically, thalidomide and various related compounds such as thalidomide precursors, analogs, metabolites and hydrolysis products have been shown to inhibit angiogenesis. Importantly, these compounds can be administered orally.

1. A method of treating undesired angiogenesis in a human or animal comprising the step of administering to the human or animal with the undesired angiogenesis a composition comprising an effective amount of an angiogenesis-inhibiting compound selected from the group consisting of 3-amothalidomide, and 3-hydroxythalidomide, and metabolities or hydrolysis products of 3-aminothalidomide and metabolites or hydrolysis products of 3-hydroxythalidomide, and mixtures thereof. 
     
     
       2. The method of  claim 1 , wherein the undesired angiogenesis is associated with retinal neovascularization. 
     
     
       3. The method of  claim 1 , wherein the undesired angiogenesis is associated with choroidal neovascularization. 
     
     
       4. The method of  claim 1  wherein the undesired angiogenesis is associated with diabetic retinopathy. 
     
     
       5. The method of  claim 1 , wherein the undesired angiogenesis is associated with macular degeneration. 
     
     
       6. The method of  claim 1 , wherein the undesired angiogenesis is associated with corneal neovascularization. 
     
     
       7. The method of  claim 1  wherein the undesired angiogenesis occurs in retinopathy of prematurity. 
     
     
       8. The method of  claim 1  wherein the undesired angiogenesis occurs in corneal graft rejection. 
     
     
       9. The method of  claim 1  wherein the undesired angiogenesis occurs in neovascular glaucoma. 
     
     
       10. The method of  claim 1  wherein the undesired angiogenesis occurs in retrolental fibroplasia. 
     
     
       11. The method of  claim 1  wherein the undesired angiogenesis occurs in epidemic keratoconjunctivitis. 
     
     
       12. The method of  claim 1  wherein the undesired angiogenesis occurs due to Vitamin A deficiency. 
     
     
       13. The method of  claim 1  wherein the undesired angiogenesis occurs due to contact lens overwear. 
     
     
       14. The method of  claim 1  wherein the undesired angiogenesis occurs in stopitc keratitis. 
     
     
       15. The method of  claim 1  wherein the undesired angiogenesis occurs in superior limbic keratitis. 
     
     
       16. The method of  claim 1  wherein the undesired angiogenesis occurs in pterygium keratitis sicca. 
     
     
       17. The method of  claim 1  wherein the undesired angiogenesis occurs in sjogrens. 
     
     
       18. The method of  claim 1  wherein the undesired angiogenesis occurs in acne rosacea. 
     
     
       19. The method of  claim 1  wherein the undesired angiogenesis occurs in phylectemolosis. 
     
     
       20. The method of  claim 1  wherein the undesired angiogenesis occurs in syhilis. 
     
     
       21. The method of  claim 1  wherein the undesired angiogenesis occurs in Myobacteria infections other than leprosy. 
     
     
       22. The method of  claim 1  wherein the undesired angiogenesis occurs in lipid degeneration. 
     
     
       23. The method of  claim 1  wherein the undesired angiogenesis occurs in chemical burns. 
     
     
       24. The method of  claim 1  wherein the undesired angiogenesis occurs in bacterial ulcers. 
     
     
       25. The method of  claim 1  wherein the undesired angiogenesis occurs in fungal ulcers. 
     
     
       26. The method of  claim 1  wherein the undesired angiogenesis occurs in Herpes simplex infections. 
     
     
       27. The method of  claim 1  wherein the undesired angiogenesis occurs in Herpes zoster infections. 
     
     
       28. The method of  claim 1  wherein the undesired angiogenesis occurs in protozona infections. 
     
     
       29. The method of  claim 1  wherein the undesired angiogenesis occurs in Kaposi's sarcoma. 
     
     
       30. The method of  claim 1  wherein the undesired angiogenesis occurs in Mooren ulcer. 
     
     
       31. The method of  claim 1  wherein the undesired angiogenesis occurs in Terrien's marginal degeneration. 
     
     
       32. The method of  claim 1  wherein the undesired angiogenesis occurs in marginal keratolysis. 
     
     
       33. The method of  claim 1  wherein the undesired angiogenesis is caused by trauma. 
     
     
       34. The method of  claim 1  wherein the undesired angiogenesis occurs in rheumatoid arthritis. 
     
     
       35. The method of  claim 1  wherein the undesired angiogenesis occurs in systemic lupus. 
     
     
       36. The method of  claim 1  wherein the undesired angiogenesis occurs in polyarteritis. 
     
     
       37. The method of  claim 1  wherein the undesired angiogenesis occurs in Wegeners sarcoidosis. 
     
     
       38. The method of  claim 1  wherein the undesired angiogenesis occurs in scleritis. 
     
     
       39. The method of  claim 1  wherein the undesired angiogenesis occurs in Steven's Johnson disease. 
     
     
       40. The method of  claim 1  wherein the undesired angiogenesis occurs in radial keratotomy. 
     
     
       41. The method of  claim 1  wherein the undesired angiogenesis occurs in sickle cell anemia. 
     
     
       42. The method of  claim 1  wherein the undesired angiogenesis occurs in sarcoid. 
     
     
       43. The method of  claim 1  wherein the undesired angiogenesis occurs in pseudoxanthoma elasticum. 
     
     
       44. The method of  claim 1  wherein the undesired angiogenesis occurs in Pagets disease. 
     
     
       45. The method of  claim 1  wherein the undesired angiogenesis occurs in vein occlusion. 
     
     
       46. The method of  claim 1  wherein the undesired angiogenesis occurs in artery occlusion. 
     
     
       47. The method of  claim 1  wherein the undesired angiogenesis occurs in carotid obstructive disease. 
     
     
       48. The method of  claim 1  wherein the undesired angiogenesis occurs in chronic uvetitis. 
     
     
       49. The method of  claim 1  wherein the undesired angiogenesis occurs in chronic vitritis. 
     
     
       50. The method of  claim 1  wherein the undesired angiogenesis occurs in Lyme's disease. 
     
     
       51. The method of  claim 1  wherein the undesired angiogenesis occurs in Eales disease. 
     
     
       52. The method of  claim 1  wherein the undesired angiogenesis occurs in Bechets disease. 
     
     
       53. The method of  claim 1  wherein the undesired angiogenesis occurs in myopis. 
     
     
       54. The method of  claim 1  wherein the undesired angiogenesis occurs in optic pits. 
     
     
       55. The method of  claim 1  wherein the undesired angiogenesis occurs in Stargarts disease. 
     
     
       56. The method of  claim 1  wherein the undesired angiogenesis occurs in pars planitis. 
     
     
       57. The method of  claim 1  wherein the undesired angiogenesis occurs is chronic retinal detachment. 
     
     
       58. The method of  claim 1  wherein the undesired angiogenesis occurs in hyperviscosity syndromes. 
     
     
       59. The method of  claim 1  wherein the undesired angiogenesis occurs in toxoplasmosis. 
     
     
       60. The method of  claim 1  wherein the undesired angiogenesis occurs in post-laser complications. 
     
     
       61. The method of  claim 1  wherein the undesired angiogenesis occurs in abnormal proliferation of fibrovascular tissue. 
     
     
       62. The method of  claim 1  wherein the undesired angiogenesis occurs in hemangiomas. 
     
     
       63. The method of  claim 1  wherein the undesired angiogenesis occurs in Osler-Weber-Rendu. 
     
     
       64. The method of  claim 1  wherein the undesired angiogenesis occurs in solid tumors. 
     
     
       65. The method of  claim 1  wherein the undesired angiogenesis occurs in blood borne tumors. 
     
     
       66. The method of  claim 1  wherein the undesired angiogenesis occurs in acquired immune deficiency syndrome. 
     
     
       67. The method of  claim 1  wherein the undesired angiogenesis occurs in occular neovascular disease. 
     
     
       68. The method of  claim 1  wherein the undesired angiogenesis occurs in osteoarthritis. 
     
     
       69. The method of  claim 1  wherein the undesired angiogenesis occurs in diseases caused by chronic inflammation. 
     
     
       70. The method of  claim 1  wherein the undesired angiogenesis occurs in Chron's disease. 
     
     
       71. The method of  claim 1  wherein the undesired angiogenesis occurs in ulceritive colitis. 
     
     
       72. The method of  claim 1  wherein the undesired angiogenesis occurs in the tumors of rhabdomyosarcoma. 
     
     
       73. The method of  claim 1  wherein the undesired angiogenesis occurs in the tumors of retinoblastoma. 
     
     
       74. The method of  claim 1  wherein the undesired angiogenesis occurs in the tumors of Ewing sarcoma. 
     
     
       75. The method of  claim 1  wherein the undesired angiogenesis occurs in the tumors of neuroblastoma. 
     
     
       76. The method of  claim 1  wherein the undesired angiogenesis occurs in the tumors of osteosarcoma. 
     
     
       77. The method of  claim 1  wherein the undesired angiogenesis occurs in leukemia. 
     
     
       78. The method of  claim 1  wherein the undesired angiogenesis occurs in psoriasis. 
     
     
       79. The method of  claim 1  wherein the undesired angiogenesis occurs in atherosclerosis. 
     
     
       80. The method of  claim 1  wherein the undesired angiogenesis occurs in pemphigoid. 
     
     
       81. A method of treating undesired angiogenesis in a human or animal comprising administering to the human or animal with the undesired angiogenesis a composition comprising an effective amount of  3 - hydroxythalidomide, wherein the undesired angiogenesis is associated with retinal neovascularization, choroidal neovascularization, diabetic retinopathy, macular degeneration, corneal neovascularization, retinopathy of prematurity, corneal graft rejection, neovascular glaucoma, retrolental fibroplasia, epidemic keratoconjunctivitis, Vitamin A deficiency, contact lens overwear, atopic keratitis, superior limbic keratitis, pterygium keratitis sicca, sjorgrens, acne rosacea, phyletenulosis, syphilis, Mycobacteria infections other than leprosy, lipid degeneration, chemical burns, bacterial ulcers, fungal ulcers, Herpes simplex infections, Herpes zoster infections, protozoan infections, Kaposi's sarcoma, Mooren ulcer, Terrien's marginal degeneration, marginal keratolysis, trauma, rheumatoid arthritis, systemic lupus, polyarteritis, Wegeners sarcoidosis, scleritis, Steven's Johnson disease, radial keratotomy, sickle cell anemia, sarcoid, pseudoxanthoma elasticium, Pagets disease, vein occlusion, artery occlusion, carotid obstructive disease, chronic uveitus, chronic vitritis, Lyme's disease, Eales disease, Bechets disease, myopia, optic pits, Stargarts disease, pars planitis, chronic retinal detachment, hyperviscosity syndromes, toxoplasmoisis, post - laser complications, abnormal proliferation of fibrovascular tissue, hemangiomas, Osler - Weber - Rendu disease solid tumors, blood borne tumors, acquired immune deficiency syndrome, ocular neovascular disease, osteoarthritis, Crohn's disease, ulcerative colitis, rhabdomyosarcoma, retinoblastoma, Ewing sarcoma, neuroblastoma, osteosarcoma, leukemia, psoriasis, atherosclerosis or pemphigoid.