2,2-difluoropropionamide derivatives of bardoxolone methyl, polymorphic forms and methods of use thereof
The present invention relates generally to the compound: N-((4aS,6aR,6bS,8aR,12aS,14aR,14bS)-11-cyano-2,2,6a,6b,9,9,12a-heptamethyl-10,14-dioxo-1,2,3,4,4a,5,6,6a,6b,7,8,8a,9,10,12a,14,14a,14b-octadecahydropicen-4a-yl)-2,2-difluoropropanamide, polymorphic forms thereof, methods for preparation and use thereof, pharmaceutical compositions thereof, and kits and articles of manufacture thereof.
1. A method of treating a condition associated with inflammation or oxidative stress in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of the pharmaceutical composition comprising an active ingredient comprising a polymorphic form of a compound having the formula:
wherein the polymorphic form is crystalline, having an X-ray powder diffraction pattern (CuKα) comprising peaks at about (a) 10.601, 11.638, 12.121, 13.021, 13,435, 15.418, 15.760, 17.830, 18.753, and 19.671 °2θ, or (b) 7.552, 10.339, 11.159, 12.107, 14.729, 15.329, 15.857, 16.824, 17.994, 18.344, 19.444, 19.764, 20.801, and 22.414 °2θ; and
a pharmaceutically acceptable carrier,
wherein the condition is an eye disorder selected from the group consisting of uveitis, macular degeneration, glaucoma, diabetic macular edema, blepharitis, diabetic retinopathy, post-surgical inflammation, dry eye, ocular inflammation, and conjunctivitis.
2. The method of claim 1 , wherein the eye disorder is macular degeneration.
3. The method of claim 2 , wherein the macular degeneration is the dry form.
4. The method of claim 2 , wherein the macular degeneration is the wet form.
5. The method of claim 1 , wherein the pharmaceutical composition is administered in a single dose per day.
6. The method of claim 1 , wherein the pharmaceutical composition is administered in more than one dose per day.
7. The method of claim 1 , wherein the pharmaceutical composition is administered topically.
8. The method of claim 7 , wherein the topical administration is administered to the eye.
9. The method of claim 1 , wherein the pharmaceutical composition is administered intraocularly.
10. The method of claim 1 , wherein the patient is a human.
11. The method of claim 1 , wherein the patient is a non-human animal.
12. The method of claim 1 , wherein the pharmaceutical formulation further comprises an agent that enhances solubility and dispersibility.
13. The method of claim 1 , wherein the polymorphic form is suspended in sesame oil.
14. The method of claim 1 , wherein the amount of the active ingredient is from 0.01% to 3% by weight.
15. The method of claim 1 , wherein the conjunctivitis is allergic conjunctivitis.