Treatment of ocular disease

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.

Description

CROSS REFERENCE TO RELATED APPLICATIONS

[0001] This application is a continuation of U.S. application Ser. No. 10 / 631,143, filed Jul. 31, 2003.FIELD OF THE INVENTION

[0002] The invention is directed to the use of rapamycin and ascomycin for therapeutic treatment of ocular conditions, including dry eye disease. BACKGROUND

[0003] Dry eye disease encompasses any condition where the tear film loses water and becomes more concentrated. It is a common complaint, affecting three million people in the United States alone, yet it is difficult to diagnose and treat. The loss of water from the tear film causes a corresponding rise in tear osmolarity. The increased osmolarity results in symptoms such as a sandy-gritty feeling in the eye, burning, irritation, or a foreign-body sensation that worsens during the day. Patients suffering from dry eye disease complain of mild to severe symptoms, with signs ranging from minimal superficial punctate keratitis to corneal perforation.

[0004] Dry eye dise...

Examples

Embodiment Construction

[0017] Methods are disclosed to ameliorate ocular conditions in need of treatment by intraocularly administering compositions containing rapamycin, ascomycin, and / or combinations of rapamycin and ascomycin as an active component. Intraocular administration provides direct effects to the eye while avoiding problems associated with systemic administration.

[0018] Rapamycin is also known as sirolimus, RAPA and Rapamune. It is a triene macrolide antibiotic derived from Streptomyces hydroscopicus and originally developed as an antifungal agent. Subsequently, it has shown anti-inflammatory, anti-tumor, and immunosuppressive properties.

[0019] Ascomycin is also known as pimecrolimus, Immunomycin, and FR-900520. It is an ethyl analog of tacrolimus (FK506) and has strong immunosuppressant properties. It inhibits Th1 and Th2 cytokines, and preferentially inhibits activation of mast cells, and is used to treat contact dermatitis and other dermatological conditions. Rapamycin and ascomycin are ...

CROSS REFERENCE TO RELATED APPLICATIONS

[0001] This application is a continuation of U.S. application Ser. No. 10 / 631,143, filed Jul. 31, 2003.FIELD OF THE INVENTION

[0002] The invention is directed to the use of rapamycin and ascomycin for therapeutic treatment of ocular conditions, including dry eye disease. BACKGROUND

[0003] Dry eye disease encompasses any condition where the tear film loses water and becomes more concentrated. It is a common complaint, affecting three million people in the United States alone, yet it is difficult to diagnose and treat. The loss of water from the tear film causes a corresponding rise in tear osmolarity. The increased osmolarity results in symptoms such as a sandy-gritty feeling in the eye, burning, irritation, or a foreign-body sensation that worsens during the day. Patients suffering from dry eye disease complain of mild to severe symptoms, with signs ranging from minimal superficial punctate keratitis to corneal perforation.

[0004] Dry eye dise...

Examples

Embodiment Construction

[0017] Methods are disclosed to ameliorate ocular conditions in need of treatment by intraocularly administering compositions containing rapamycin, ascomycin, and / or combinations of rapamycin and ascomycin as an active component. Intraocular administration provides direct effects to the eye while avoiding problems associated with systemic administration.

[0018] Rapamycin is also known as sirolimus, RAPA and Rapamune. It is a triene macrolide antibiotic derived from Streptomyces hydroscopicus and originally developed as an antifungal agent. Subsequently, it has shown anti-inflammatory, anti-tumor, and immunosuppressive properties.

[0019] Ascomycin is also known as pimecrolimus, Immunomycin, and FR-900520. It is an ethyl analog of tacrolimus (FK506) and has strong immunosuppressant properties. It inhibits Th1 and Th2 cytokines, and preferentially inhibits activation of mast cells, and is used to treat contact dermatitis and other dermatological conditions. Rapamycin and ascomycin are ...