Treatment of ocular disease

• US 7,083,802 B2
• Filed: 07/31/2003
• Issued: 08/01/2006
• Est. Priority Date: 07/31/2003
• Status: Expired due to Fees

• Current Assignee: Gholam A. Peyman
• Original Assignee: Advanced Ocular Systems Limited (IFS Construction Services Ltd.)
• Inventors: Peyman, Gholam
• Primary Examiner(s): Sheikh, Humera N.
• Application Number:
  US10/631,143
• Publication Number:
  US 20050025810A1
• Time in Patent Office: 1,097 Days
• Field of Search: 424/400, 424/422, 424/423, 424/427, 424/428
• US Class Current: 424/422
• CPC Class Codes: A61K 31/33 Heterocyclic compounds
• CPC Class Codes: A61K 31/4745 condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines yohimbine derivatives, vinblastine A61K31/475; ergoline derivatives A61K31/48
• CPC Class Codes: A61K 9/0051 Ocular inserts, ocular implants
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 19/08 for bone diseases, e.g. rachitism, Paget's disease
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 27/12 for cataracts
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 33/02 Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 37/08 Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

Abstract

A formulation to treat ocular conditions such as dry eye disease, as well as other conditions, is disclosed. Rapamycin and/or ascomycin is administered intraocularly, such as by topical application, injection into the eye, or implantation in or on the eye. For example, a topical administration may contain between about 50 pg/ml drug to about 50 μg/ml drug in a formulation which may be applied at bedtime or throughout the day. For injection, a dose of about 50 pg/ml to about 200 μg/ml may be used. Rapamycin and/or ascomycin may also be administered in milligram quantities as a surgical implant, for example, in a diffusible walled reservoir sutured to the wall of the sclera, or may be contained within an inert carrier such as microspheres or liposomes to provide a slow-release drug delivery system.

Claims

1. A method to treat a posterior segment ocular condition selected from diabetic retinopathy, retinitis pigmentosa, or age related macular degeneration in a patient comprising intraocularly administering a composition comprising a drug selected from the group consisting of rapamycin, ascomycin, and combinations thereof, the drug at a concentration up to about 200 μ

g/ml in a pharmaceutically acceptable formulation effective to treat the diabetic retinopathy, retinitis pigmentosa, or age related macular degeneration condition without substantial toxicity wherein the composition is administered by at least one of intraocular injection.

2. The method of claim 1 wherein the composition further comprises Cyclosporin A, tacrolimus, or combinations thereof.

3. A method to treat a posterior segment ocular condition selected from diabetic retinopathy, retinitis pigmentosa, or age related macular degeneration in a patient comprising intraocularly administering a composition consisting essentially of rapamycin in a pharmaceutically acceptable formulation effective to treat the diabetic retinopathy, retinitis pigmentosa, or age related macular degeneration condition by a method selected from the group consisting of topical administration at a concentration of about 50 pg/ml to less than 1 μ

g/ml, subconjunctival injection at a dose in the range of about 1 ng/ml to about 200 μ

g/ml, intravitreal injection at a dose in the range of about 1 ng/0.1 ml to about 200 μ

g/ml, or retrobulbar injection at a dose in the range of about 20 μ

g/ml to about 200 μ

g/ml.

4. The method of claim 3 wherein injection is intravitreal at a dose of about 50 μ

g/0.1 ml.

5. An ocular treatment method comprising intraocularly administering to a patient after corneal surgery a composition consisting essentially of rapamycin in a pharmaceutically acceptable formulation and in an amount effective to enhance post-surgical ocular moisture in the patient wherein the composition is administered at a concentration up to about 200 μ

g/ml by at least one of intraocular injection, or the composition is administered topically at a concentration in the range between about 50 pg/ml to less than 1 μ

g/ml.

6. The method of claim 5 wherein the composition is administered by subconjunctival injection at a dose in the range of about 1 ng/ml to about 200 μ

g/ml, intravitreal injection at a dose in the range of about 1 ng/0.1 ml to about 200 μ

g/ml, or retrobulbar injection at a dose in the range of about 20 μ

g/ml to about 200 μ

g/ml.

7. An ocular treatment method comprising intraocularly administering to a patient after corneal surgery a composition consisting essentially of ascomycin in a pharmaceutically acceptable formulation and in an amount effective to enhance post-surgical ocular moisture in the patient wherein the composition is administered at a concentration up to about 200 μ

g/ml by at least one of intraocular injection, or the composition is administered topically at a concentration in the range between about 50 pg/ml to less than 1 μ

g/ml.

8. The method of claim 7 wherein the composition is administered by subconjunctival injection at a dose in the range of about 1 ng/ml to about 200 μ

g/ml, intravitreal injection at a dose in the range of about 1 ng/0.1 ml to about 200 μ

g/ml, or retrobulbar injection at a dose in the range of about 20 μ

g/ml to about 200 μ

g/ml.

9. A method to treat an ocular condition in a patient comprising intraocularly administering to the patient a pharmaceutically acceptable formulation of a drug selected from the group consisting of rapamycin, ascomycin, and combinations thereof, in an amount up to about 200 μ

g/ml effective to treat an ocular condition selected from diabetic retinopathy, retinitis pigimentosa, or age related macular degeneration without substantial toxicity and at least one antibiotic, wherein the composition is administered by at least one of intraocular injection at a concentration up to about 200 μ

g/ml, or the composition is administered topically at a concentration in the range between about 50 pg/ml to less than 1 μ

g/ml.

10. A method to treat an ocular posterior segment condition selected from diabetic retinopathy, retinitis pigmentosa, or age related macular degeneration in a patient comprising intraocularly administering a composition consisting essentially of ascomycin in a pharmaceutically acceptable formulation effective to treat the diabetic retinopathy, retinitis pigmentosa, or age related macular degeneration condition by a method selected from the group consisting of topical administration at a concentration between about 50 pg/ml to less than 1 μ

g/ml, subconjunctival injection at a dose in the range of about 1 ng/ml to about 200 μ

g/ml, intravitreal injection at a dose in the range of about 1 ng/0.1 ml to about 200 μ

g/ml, or retrobulbar injection at a dose in the range of about 20 μ

g/ml to about 200 μ

g/ml.

11. The method of claim 10 wherein injection is intravitreal at a dose of about 50 μ

g/0.1 ml.