Compositions and methods for localized therapy of the eye

Abstract

Compositions, and methods of using such compositions, useful for injection into the posterior segments of human or animal eyes are provided. Such compositions include small particles of a poorly soluble therapeutic agent that facilitates formation of concentrated regions of the therapeutic agent in the retinal pigmented epithelium of an eye. The particles are formed by combining a therapeutic agent with an ophthalmically acceptable polymer component. The particles have sizes less than about 3000 nanometers, and in some cases, less than about 200 nanometers. One example of composition includes particles of triamcinolone acetonide and hyaluronic acid have a size less than about 3000 nanometers.

Description

CROSS REFERENCE TO RELATED APPLICATIONS[0001]This application claims the benefit of U.S. Provisional Application 60 / 537,620, filed Jan. 20, 2004, the entire content of which is hereby incorporated by reference.[0002]The present invention relates to compositions that are delivered to the posterior segment of an eye of a human or animal. More particularly, the invention relates to compositions including one or more poorly soluble therapeutic agents present in particles that are sized and / or distributed to provide localized therapy to the posterior of an eye.[0003]Corticosteroids, among other agents, are utilized to treat a wide variety of ophthalmic diseases that affect the posterior segment of an eye. Examples of some diseases treated with corticosteroids includes: central retinal vein occlusion (CRVO), branch retinal vein occlusion (BRVO), choroidal macular edema (CME), diabetic macular edema (DME), diabetic macular retinopathy, uveitis, telangitis, and age related macular degenerat...

AI Technical Summary

Benefits of technology

[0010]Reducing the lens concentration of a corticosteroid may help mitigate the cataractogenic potential of these drugs. Additionally, reducing the anterior segment concentration of the corticosteroids relative to the posterior concentrations may reduce the chance of elevating the TIGR (MYOC, GLC1A) gene activity in the trabecular meshwork thought to be associated with steroid induced glaucoma.

[0012]New compositions and methods for treating posterior segments of eyes of humans or animals have been discovered. The present compositions are highly suitable for intravitreal administration into the posterior segments of eyes and provide localized therapeutic effects to the posterior portion of an eye and reduced adverse side-effects to anterior structures or tissues of an eye.

Problems solved by technology

In treating ocular diseases or disorders, steroids can be administered systemically, however systemic administration of steroids is often associated with side effects that are generally too great for ophthalmic use.

Although direct intravitreal administration of current therapeutic agents may address some problems associated with systemic administration, intravitreal administration of existing ophthalmic compositions may result in ocular hypertension, as well as steroid glaucoma and posterior subcapsular cataracts, when steroids are administered.

In addition, the formulation currently used in clinical practice contains excipients that are toxic to the internal ocular structures.

As such, permeation of compounds into the RPE is quite limited.

Thus, regardless of the administration route, penetration of a therapeutic agent through the outer blood-retinal barrier is limited.

To overcome these limitations extremely high and potentially toxic doses of drugs are frequently used.

Unfortunately, side effects from the existing triamcinolone acetonide formulation include endophthalmitis as well as retinal toxicity from the benzyl alcohol preservative.