INJECTABLE DEPOT FORMULATIONS
Disclosed are compositions and methods related to the use of kinase inhibitors in treating macular degeneration and/or retinal vein occlusion.
1 . An injectable composition, comprising a poorly water-soluble kinase inhibitor dissolved in a water-miscible organic solvent, wherein:
the concentration of the kinase inhibitor in the composition is at least 200 μg/mL; and
the concentration of the kinase inhibitor in the composition is at least 100 times higher than the solubility of the kinase inhibitor in water at 37° C.
2 . The injectable composition of claim 1 , wherein the concentration of the kinase inhibitor in the composition is at least 800 μg/mL.
3 . The injectable composition of claim 1 , wherein the concentration of the kinase inhibitor in the composition is at least 200 times higher than the solubility of the kinase inhibitor in water at 37° C.
4 . The injectable composition of claim 1 , wherein the solubility of the kinase inhibitor in water is less than 10 μg/mL.
5 . The injectable composition of claim 1 , wherein the organic solvent is ethanol.
6 . The injectable composition claim 1 , wherein the kinase inhibitor is selected from bafetinib, bosutinib, dasatinib, imatinib, nilotinib, ponatinib, radotinib, and SU6656.
7 . The injectable composition of claim 1 , wherein the kinase inhibitor is selected from apatinib, axitinib, cabozantinib, cediranib, crenolanib, foretinib, lenvatinib, linifanib, masitinib, motesanib, nintedanib, pazopanib, pegaptanib, regorafenib, semaxanib, sorafenib, sunitinib, tivozanib, toceranib, vandetanib, and vatalanib.
8 . The injectable composition of claim 7 , wherein the kinase inhibitor is sorafenib.
9 . The injectable composition of claim 8 , wherein:
the kinase inhibitor is sorafenib; and
the concentration of the kinase inhibitor is about 800 μg/mL to about 4000 μg/mL.
10 . The injectable composition of claim 1 , wherein the composition is a liquid.
11 - 14 . (canceled)
15 . A syringe comprising the injectable composition of claim 1 .
16 - 19 . (canceled)
20 . The syringe of claim 15 , further comprising a filter.
21 . The syringe of claim 20 , wherein the filter comprises pores with a pore size of about 0.2 μm to about 5 μm.
22 . (canceled)
23 . The syringe of claim 20 , further comprising a needle, wherein the needle is about 0.25 inches long to about 1.0 inches long.
24 - 26 . (canceled)
27 . The syringe of claim 23 , wherein the needle is about 28 gauge to about 33 gauge.
28 . The syringe of claim 27 , wherein the needle is 29 gauge, 30 gauge, 31 gauge, or 32 gauge.
29 . A kit comprising a vial comprising the injectable composition of claim 1 and a syringe.
30 . A method for preventing or treating an eye disease in a subject, comprising injecting the composition of claim 1 into the vitreous of an eye of the subject.
31 . The method of claim 30 , comprising injecting about 10 μL to about 100 μL of the composition into the vitreous of the eye.
32 . The method of claim 31 , comprising injecting about 50 μL of the composition into the vitreous of the eye.
33 . The method of claim 30 , comprising filtering the composition prior to injecting the composition into the eye.
34 . (canceled)
35 . The method of claim 30 , wherein the subject is selected from rodents, lagomorphs, ovines, porcines, canines, felines, equines, bovines, and primates.
36 . The method of claim 35 , wherein the subject is a human.
37 . The method of claim 30 , wherein:
the subject has age-related macular degeneration, dry macular degeneration, wet macular degeneration, geographic atrophy, vision loss, non-ischemic retinal vein occlusion, or ischemic retinal vein occlusion; or
the subject is at risk of developing wet age-related macular degeneration, geographic atrophy, or vision loss.
38 - 47 . (canceled)