Liquid formulations for treatment of diseases or conditions
Diseases and conditions associated with tissues of the body, including but not limited to tissues in the eye, can be effectively treated, prevented, inhibited, onset delayed, or regression caused by administering therapeutic agents to those tissues. Described herein are liquid formulations which deliver a variety of therapeutic agents, including but not limited to rapamycin, to a subject for an extended period of time; liquid formulations which form a non-dispersed mass when placed in an aqueous medium of a subject; non-dispersed mass-forming liquid formulations which form a gel or gel-like substance in an aqueous medium; liquid formulations, comprising a therapeutic agent and a plurality of polymers; and methods for delivering therapeutic agents to a subject for an extended period of time using the liquid formulations. The liquid formulation may be placed in an aqueous medium of a subject, including but not limited to via intraocular or periocular administration, or placement proximate to a site of a disease or condition to be treated in a subject. A method may be used to administer rapamycin to treat or prevent angiogenesis, choroidal neovascularization, or age-related macular degeneration, or wet age-related macular degeneration in a subject. The liquid formulations may comprise rapamycin or other therapeutic agents.
1. A method for treating uveitis in a human subject, the method comprising
administering to the human subject by intravitreal injection a volume of a liquid formulation comprising an effective amount of a therapeutic agent to treat uveitis in the human subject for at least two months,
wherein the liquid formulation comprises the therapeutic agent, polyethylene glycol and ethanol,
wherein the therapeutic agent is selected from the group consisting of rapamycin, and pharmaceutically acceptable salts thereof,
wherein the liquid formulation is a liquid solution that forms a non-dispersed mass when injected into the vitreous, and
wherein the therapeutic agent comprises between 0.5% to 6.0% of the total weight of the liquid formulation, and the polyethylene glycol comprises between 80% to 99% of the total weight of the liquid formulation.
2. The method of claim 1 , wherein the polyethylene glycol and the ethanol diffuse out of the non-dispersed mass upon said injection leaving a precipitate of the therapeutic agent.
3. The method of claim 1 , wherein the non-dispersed mass does not form a gel or gel-like substance upon injection.
4. The method of claim 1 , wherein the liquid formulation has a viscosity of between 40 and 120 centipoise.
5. The method of claim 1 , wherein the liquid formulation as a viscosity of between 60 and 80 centipoise.
6. The method of claim 1 , wherein the therapeutic agent is rapamycin.
7. The method of claim 1 , wherein the uveitis is chronic uveitis.
8. The method of claim 6 , wherein the liquid formulation comprises about 2% (w/w) rapamycin, about 94% (w/w) PEG 400, and about 4% (w/w) ethanol.
9. The method of claim 6 , wherein the volume of liquid formulation contains between 20 μg to 2 mg rapamycin.
10. The method of claim 1 , wherein the therapeutic agent comprises between 0.628% to 5.233% of the total weight of the liquid formulation.
11. The method of claim 1 , wherein the therapeutic agent comprises between 1% to 5% of the total weight of the liquid formulation.
12. The method of claim 1 , wherein the polyethylene glycol is PEG 300 or PEG 400.
13. The method of claim 1 , wherein the polyethylene glycol is PEG 400.
14. The method of claim 1 , comprises administering to the human subject by intravitreal injection a volume of a liquid formulation comprising an effective amount of a therapeutic agent to treat uveitis in the human subject for two to three months.