Formulations for treating ocular diseases and conditions

• US 8,663,639 B2
• Filed: 08/18/2008
• Issued: 03/04/2014
• Est. Priority Date: 02/09/2005
• Status: Active Grant

• Current Assignee: Santen Pharmaceutical Company Limited
• Original Assignee: Santen Pharmaceutical Company Limited
• Inventors: Dor, Philippe J. M., Mudumba, Sreenivasu, Nivaggioli, Thierry, Weber, David A., Farooq, Sidiq, Takhar, Sudeep
• Primary Examiner(s): BASQUILL, SEAN M
• Application Number:
  US12/193,686
• Publication Number:
  US 20090074786A1
• Time in Patent Office: 2,024 Days
• Field of Search: 424/141.1, 514/291
• US Class Current: 424/141.1
• CPC Class Codes: A61K 31/436 the heterocyclic ring system containing a six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin
• CPC Class Codes: A61P 27/02 Ophthalmic agents

Abstract

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.

Claims

1. A method for treating wet age-related macular degeneration in a human subject by repeated administration of a first formulation and a second formulation, the method comprising:

(a) administering to the human subject two or more doses of a volume of the first formulation by intravitreal placement, wherein the volume of the first formulation comprises an amount of and about 500 μ

g of ranibizumab; and

(b) administering to the human subject two or more doses of a volume of the second formulation by intravitreal or subconjuctival placement, wherein the volume of the second formulation comprises an amount of between about 200 μ

g and about 2000 μ

g of rapamycin, or a pharmaceutically acceptable salt or ester thereof;

wherein the administration of rapamycin or a pharmaceutically acceptable salt or ester thereof decreases the frequency at which ranibizumab is administered to treat wet age-related macular degeneration in the human subject.

2. The method of claim 1, wherein step (a) is coincident with step (b).

3. The method of claim 1, wherein step (b) is subsequent to step (a).

4. The method of claim 1, wherein step (b) is prior to step (a).

5. The method of claim 1, wherein the volume of the second formulation contains a rapamycin dose selected from the group consisting of about 220 μ

g, about 440 μ

g, about 880 μ

g, and about 1320 μ

g of rapamycin.

6. The method of claim 1, wherein the second formulation is a liquid solution that consists essentially of about 2% (w/w) rapamycin, about 4% (w/w) ethanol, and about 94% (w/w) polyethylene glycol 400 (PEG 400).

7. The method of claim 1, wherein the second formulation is a liquid solution that consists essentially of about 4% (w/w) rapamycin, about 4% (w/w) ethanol, and about 92% (w/w) polyethylene glycol 400 (PEG 400).

8. The method of claim 1, wherein the second formulation is a liquid solution that consists essentially of about 1% (w/w) rapamycin, about 4% (w/w) ethanol, and about 95% (w/w) polyethylene glycol 400 (PEG 400).

9. The method of claim 1, wherein the second formulation is a solution of rapamycin dissolved in a solvent system.

10. The method of claim 9, wherein the solvent system comprises polyethylene glycol.

11. The method of claim 10, wherein the solvent system further comprises ethanol.