Liquid formulations for treatment of diseases or conditions

Abstract

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; 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. A method may be used to administer rapamycin to treat or prevent angiogenesis, choroidal neovascularization, or age-related macular degeneration in a subject.

1 . A method for treating age-related macular degeneration (AMD) 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 AMD in the human subject for at least one month, wherein   the liquid formulation comprises between 0.5% (w/w) to 6.0% (w/w) of the therapeutic agent, between 80% (w/w) to 99% (w/w) of polyethylene glycol, and ethanol,   the therapeutic agent is rapamycin or a pharmaceutical acceptable salt thereof,   the AMD is selected from the group consisting of dry form of AMD, wet form of the AMD and transition from the dry form of AMD to the wet form of AMD, and   the liquid formulation is a liquid solution that forms a non-dispersed mass when injected into the vitreous.   
     
     
         2 . The method of  claim 1 , wherein the AMD is the dry form of AMD. 
     
     
         3 . The method of  claim 1 , wherein the at least one month is at least two months. 
     
     
         4 . The method of  claim 1 , wherein the at least one month is at least three months. 
     
     
         5 . 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. 
     
     
         6 . The method of  claim 1 , wherein the non-dispersed mass does not form a gel or gel-like substance upon injection. 
     
     
         7 . The method of  claim 1 , wherein the liquid formulation has a viscosity of between 40 and 120 centipoise. 
     
     
         8 . The method of  claim 1 , wherein the liquid formulation as a viscosity of between 60 and 80 centipoise. 
     
     
         9 . The method of  claim 1 , wherein the therapeutic agent is rapamycin. 
     
     
         10 . The method of  claim 2 , wherein the AMD is the wet form of AMD. 
     
     
         11 . The method of  claim 9 , wherein the liquid formulation comprises about 2% (w/w) rapamycin, about 94% (w/w) PEG 400, and about 4% (w/w) ethanol. 
     
     
         12 . The method of  claim 9 , wherein the volume of liquid formulation contains between 20 μg to 2 mg rapamycin. 
     
     
         13 . The method of  claim 1 , wherein the therapeutic agent comprises between 0.628% to 5.233% of the total weight of the liquid formulation. 
     
     
         14 . The method of  claim 1 , wherein the therapeutic agent comprises between 1% to 5% of the total weight of the liquid formulation. 
     
     
         15 . The method of  claim 1 , wherein the polyethylene glycol is PEG 300 or PEG 400. 
     
     
         16 . The method of  claim 1 , wherein the polyethylene glycol is PEG 400. 
     
     
         17 . The method of  claim 1 , wherein the at least one month is from one to three months. 
     
     
         18 . The method of  claim 1 , wherein the AMD is the transition from the dry form of AMD to the wet form of AMD. 
     
     
         19 . A method of administering a liquid formulation, the method comprising:
 administering to a human subject by intravitreal injection a volume of a liquid formulation comprising between 0.5% (w/w) to 6.0% (w/w) of a therapeutic agent, between 80% (w/w) to 99% (w/w) of polyethylene glycol, and ethanol, wherein   the therapeutic agent is rapamycin or a pharmaceutical acceptable salt thereof,   the human subject has a form of age-related macular degeneration (AMD) selected from the group consisting of dry form of AMD, wet form of the AMD and transition from the dry form of AMD to the wet form of AMD, and   the liquid formulation is a liquid solution that forms a non-dispersed mass when injected into the vitreous.   
     
     
         20 . The method of  claim 19 , wherein the administering is done once every two to three months. 
     
     
         21 . The method of  claim 19 , wherein the therapeutic agent is rapamycin.