Use of a steroid prodrug for the treatment of disease of the posterior segment of the eye

Abstract

Use of a composition comprising at least one prodrug of a steroid, preferably of a corticosteroid, for the preparation of an ophthalmic composition intended for the treatment of an ocular condition or disease of a human being or an animal.

1 . A method for the treatment of an ocular condition or disease of a human being or an animal, comprising administering to said human or animal in need thereof at least one prodrug of a steroid in the form of a medicament or ophthalmic composition said medicament or ophthalmic composition being administered by invasive means, preferably by intraocular injection. 
     
     
         2 . The method according to the  claim 1 , wherein the prodrug is a long chain ester of steroid, preferably of corticosteroid, said ester group comprising an alkyl group of more than 10 carbons preferentially of more than 14 carbons, even more preferentially of 16 carbons. 
     
     
         3 . The method according to  claim 1 , wherein the steroid is selected from the group consisting of alclometasone dipropionate, amcinonide, amcinafel, amcinafide, beclamethasone, betamethasone, betamethasone dipropionate, betamethasone valerate, clobetasone propionate, chloroprednisone, clocortelone, Cortisol, cortisone, cortodoxone, difluorosone diacetate, descinolone, desonide, defluprednate, dihydroxycortisone, desoximetasone, dexamethasone, deflazacort, diflorasone, diflorasone diacetate, dichlorisone, esters of betamethasone, fluazacort, flucetonide, flucloronide, fludrotisone, fluorocortisone, flumethasone, flunisolide, fluocinonide, fluocinolone, fluocinolone acetonide, flucortolone, fluperolone, fluprednisolone, fluroandrenolone acetonide, fluocinolone acetonide, flurandrenolide, fluorametholone, fluticasone propionate, hydrocortisone, hydrocortisone butyrate, hydrocortisone valerate, hydrocortamate, loteprendol, medrysone, meprednisone, methylprednisone, methylprednisolone, mometasone furoate, paramethasone, paramethasone acetate, prednisone, prednisolone, prednidone, triamcinolone acetonide, triamcinolone hexacatonide, and triamcinolone, salts, derivatives, and a mixture thereof. 
     
     
         4 . The method according to  claim 1 , wherein the steroid is selected from the group consisting of cortisone, dexamethasone, fluocinolone, hydrocortisone, methylprednisolone, prednisolone, prednisone, and triamcinolone. 
     
     
         5 . The method according to  claim 1 , wherein the prodrug is dexamethasone palmitate. 
     
     
         6 . The method according to  claim 1 , wherein the prodrug is comprised in the composition in an amount of about 0.01% to about 10% w/w preferably about 0.5% to about 3% w/w, more preferably about 2% w/w or about 1% w/w of the composition. 
     
     
         7 . The method according to  claim 1 , wherein said prodrug is in combination with any ophthalmically acceptable excipient or carrier, or within an implant. 
     
     
         8 . The method according to  claim 7 , wherein the carrier is selected from a ophthalmic acceptable oil, phospholipid vesicles or oil-in-water emulsion or water-in-oil emulsion or any other suitable carrier. 
     
     
         9 . The method according to  claim 8  wherein the oil phase comprises at least about 1, at least about 5, at least about 10, at least about 20, at least about 30 or at least about 40 weight percent of the composition/emulsion, preferably 10% of the emulsion. 
     
     
         10 . The method according to  claim 1  wherein the administrated prodrug will gradually release through its hydrolysis by endogenous enzymes in situ, to generate therapeutic levels of the active drug. 
     
     
         11 . The method according to  claim 1 , wherein said prodrug is administered through one intraocular injection every one, two or six months. 
     
     
         12 . The method according to  claim 1 , wherein the amount of the composition of the invention administered is such that, after one month, the molar ratio drug/prodrug in the retina or in the choroid is equal or less than 1, preferentially of 0.5, more preferentially of 0.1. 
     
     
         13 . The method according to  claim 1 , wherein the disease is a condition or disease of the interior of the eye, preferably of the back of the eye. 
     
     
         14 . The method according to  claim 13 , characterized in that said diseases are: uveitis, macular edema, macular degeneration, retinal detachment, ocular tumors, bacterial, fungal but viral infections, multifocal choroiditis, diabetic retinopathy, proliferative vitreoretinopathy (PVR), sympathetic opthalmia, Vogt Koyanagi-Harada (VKH) syndrome, histoplasmosis, uveal diffusion, and vascular occlusion. 
     
     
         15 . The method according to  claim 1 , wherein the composition further comprises an active agent selected from cyclosporine, anti-VEGF, and/or an antibiotic. 
     
     
         16 . The method according to  claim 1 , wherein the composition comprises dexamethasone palmitate and at least one active agent selected from the group consisting of cyclosporine, anti-VEGF, and an antibiotic.