Liquid formulations for treatment of diseases or conditions
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 uveitis in a human subject, the method comprising
administering to the human subject by periocular 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 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, and
the liquid formulation is a liquid solution that forms a non-dispersed mass when injected between the sclera and the conjunctiva.
2. The method of claim 1 , wherein the periocular injection is subconjunctival injection.
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 9 , wherein the liquid formulation comprises about 2% (w/w) rapamycin, about 94% (w/w) PEG 400, and about 4% (w/w) ethanol.
11. The method of claim 9 , wherein the volume of liquid formulation contains between 20 μg to 2 mg rapamycin.
12. The method of claim 1 , wherein the therapeutic agent comprises between 0.628% to 5.233% of the total weight of the liquid formulation.
13. The method of claim 1 , wherein the therapeutic agent comprises between 1% to 5% of the total weight of the liquid formulation.
14. The method of claim 1 , wherein the polyethylene glycol is PEG 300 or PEG 400.
15. The method of claim 1 , wherein the polyethylene glycol is PEG 400.
16. The method of claim 1 , wherein the at least one month is from one to three months.
17. A method of administering a liquid formulation, the method comprising:
administering to a human subject by periocular 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 uveitis, and
the liquid formulation is a liquid solution that forms a non-dispersed mass when injected between the sclera and the conjunctiva.
18. The method of claim 17 , wherein the administering is done once every two to three months.
19. The method of claim 17 , wherein the therapeutic agent is rapamycin.
20. The method of claim 17 , wherein the periocular injection is subconjunctival injection.