Rapamycin formulations and methods of their use
Described herein are liquid rapamycin formulations. Described herein are methods of treating or preventing diseases or conditions, such as choroidal neovascularization, wet AMD and dry AMD, and preventing transition of dry AMD to wet AMD, using the liquid rapamycin formulations described herein.
1. A method for treating wet age-related macular degeneration in a human subject, the method comprising administering to the human subject by intraocular or periocular injection of a liquid formulation containing an amount of rapamycin effective to treat wet-age macular degeneration in the human subject, wherein the liquid formulation is a liquid solution that forms a non-dispersed mass when injected into the vitreous, and the liquid formulation comprises about 2% (w/w) rapamycin, about 94% (w/w) PEG 400, and about 4% (w/w) ethanol.
2. The method of claim 1 , wherein the volume of liquid formulation contains between 20 μg and 2.5 mg of rapamycin.
3. The method of claim 1 , wherein the volume of liquid formulation contains between 20 μg and 4 mg of rapamycin.
4. The method of claim 1 , wherein the volume of the liquid formulation is administered to the human subject by injection into the vitreous.
5. The method of claim 1 , wherein the volume of the liquid formulation is administered to the human subject by injection between the sclera and conjunctiva.
6. The method of claim 1 , wherein the volume of the liquid formulation when injected into the vitreous delivers an amount of rapamycin sufficient to achieve one or both of:
an average concentration of rapamycin in the retina choroid of at least 0.01 ng/mg for a period of time of at least 30 days following administration of the liquid formulation, and
an average concentration of rapamycin in the vitreous of at least 1000 ng/ml for a period of time of at least 30 days following administration of the liquid formulation.
7. The method of claim 1 , wherein the volume of the liquid formulation when injected between the sclera and conjunctiva delivers an amount of rapamycin sufficient to achieve one or both of:
an average concentration of rapamycin in the vitreous of at least 0.01 ng/ml for a period of time of at least 30 days following administration of the liquid formulation; and
an average concentration of rapamycin in the retina choroid of at least 0.001 ng/mg for a period of time of at least 30 days following administration of the liquid formulation.
8. The method of claim 1 , wherein the non-dispersed mass is a solid depot of rapamycin.