Title:  Upregulation of endogenous prostaglandins to lower intraocular pressure

United States Patent:  6,376,541

Assignee:  Alcon Manufacturing, Ltd. (Fort Worth, TX)

Filed:  December 6, 1999

PCT NO:  PCT/US99/26068

102(e) Date:  December 6, 1999

PCT PUB. Date:  May 18, 2000

A method of lowering intraocular pressure (IOP) employs an upregulating agent that induces increased prostaglandin synthesis in the eye. The method of treatment entails administering to the eye of a mammal in need thereof a prostaglandin upregulating agent to increase endogenous prostaglandin synthesis and thereby effect a reduction in intraocular pressure. In a preferred embodiment the upregulating agent is IL-1.

DETAILED DESCRIPTION OF THE INVENTION

The present invention involves a method of treating the eyes of a mammal suffering from a glaucomatous condition, wherein the intraocular pressure (IOP) of the eye is or is likely to become elevated above its "normal" state. The present method can be employed to reduce, or ameliorate elevated IOP and to prevent or impede increases in normal IOP, thereby controlling or slowing the progression of the disease.

A method of the present invention comprises administering to an eye of the mammal a therapeutically effective amount of a prostaglandin upregulating agent. As used herein, the term "upregulating agent" means any agent which, directly or indirectly, induces increased synthesis of a prostaglandin in the eye to effect a reduction of intraocular pressure. The method of the present invention may be practiced with any agent which directly or indirectly upregulates prostaglandin synthesis in the eye. Preferred among such upregulating agents are IL-1 beta (Genzyme, Mass., USA), TGF-beta 1 or 2 (Oncogene Research Products, Cambridge, Mass., USA), levamisole (Flavine International, Inc., Closter, N.J., USA), muramyl dipeptide (MDP) (Glycotech Corporation, Rockville, Md., USA) (see also U.S. Pat. No. 4,235,771, the disclosure of which is incorporated herein by reference), and muramyl tripeptide (MTP).

Other ingredients which may be desirable to use in the ophthalmic preparations of the present invention include preservatives, co-solvents, and viscosity building agents.

Antimicrobial Preservatives

Ophthalmic products are typically packaged in multidose form. Preservatives are thus required to prevent microbial contamination during use. Suitable preservatives include: benzalkonium chloride, thimerosal, chlorobutanol, methyl paraben, propyl paraben, phenylethyl alcohol, edetate disodium, sorbic acid, Onamer M, or other agents known to those skilled in the art. Such preservatives are typically employed at a level between about 0.001% and about 1.0% by weight.

Co-Solvents

Some upregulating agents of the present invention may have limited solubility in water and therefore may require a surfactant or other appropriate co-solvent in the composition. Such co-solvents include: Polysorbate 20, 60 and 80; Pluronic F-68, F-84 and P-103; CREMOPHORE.RTM. EL (polyoxyl 35 castor oil) cyclodextrin; or other agents known to those skilled in the art. Such co-solvents are typically employed at a level between about 0.01% and about 2% by weight.

Viscosity Agents

Viscosity greater than that of simple aqueous solutions may be desirable to increase ocular absorption of the active compound, to decrease variability in dispensing the formulations, to decrease physical separation of components of a suspension or emulsion of formulation and/or otherwise to improve the ophthalmic formulation. Such viscosity building agents include, for example, polyvinyl alcohol, polyvinyl pyrrolidone, methyl cellulose, hydroxy propyl methyl cellulose, hydroxyethyl cellulose, carboxymethyl cellulose, hydroxy propyl cellulose, chondroitin sulfate and salts thereof, hyaluronic acid and salts thereof, and other agents known to those skilled in the art. Such agents are typically employed at a level between about 0.01% and about 2% by weight.

Claim 1 of 9 Claims

What is claimed is:

1. A method of treating glaucoma or elevated intraocular pressure in an eye of a human comprising topically administering to the eye a therapeutically effective amount of a non-prostanoid prostaglandin upregulating agent that induces endogenous prostaglandin synthesis in said eye to effect a reduction in intraocular pressure.

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