|Title:||Ocular implant made by a double extrusion process|
|Abstract:||The invention provides biodegradable implants sized for implantation in an ocular region and methods for treating medical conditions of the eye. The implants are formed from a mixture of hydrophilic end and hydrophobic end PLGA, and deliver active agents into an ocular region without a high burst release.|
|Inventor(s):||Shiah; Jane-Guo (Irvine, CA), Bhagat; Rahul (Irvine, CA), Blanda; Wendy M. (Tustin, CA), Nivaggioli; Thierry (Atherton, CA), Peng; Lin (South San Francisco, CA), Chou; David (Palo Alto, CA), Weber; David A. (Danville, CA)|
|Assignee:||Allergan, Inc. (Irvine, CA)|
1. A method for treating a medical condition of the eye comprising implanting into an ocular region of the eye a bioerodible implant and delivering a therapeutic amount of an active
agent to the ocular region, wherein a) the bioerodible implant is a double extruded rod comprising an active agent homogeneously dispersed within a biodegradable polymer matrix; wherein b) the biodegradable polymer matrix comprises a mixture of
hydrophilic ended poly(D,L-lactide-co-glycolide) (PLGA) and hydrophobic ended poly(D,L-lactide-co-glycolide) (PLGA); wherein the hydrophilic- and hydrophobic-end PLGAs are milled prior to extrusion with the active agent; wherein c) the bioerodible
implant is sized for implantation in an ocular region; and wherein d) the medical condition of the eye is selected from the group consisting of uveitis, macular edema, macular degeneration, retinal detachment, ocular tumors, fungal infections, viral
infections, multifocal choroiditis, diabetic retinopathy, proliferative vitreoretinopathy (PVR), sympathetic ophthalmia, Vogt Koyanagi-Harada (VKH) syndrome, histoplasmosis, uveal diffusion, and vascular occlusion.
2. The method of claim 1, wherein the implant is implanted into the anterior chamber, posterior chamber, or vitreous cavity of the eye.
3. The method of claim 1, wherein the medical condition of the eye is uveitis and the active agent is dexamethasone.
4. The method of claim 1, wherein the mean particle size of the milled PLGAs is no greater than 20 .mu.m.
5. The method of claim 1, wherein the medical condition of the eye is macular edema and the active agent is dexamethasone.
6. The method of claim 1, wherein the active agent comprises particles of dexamethasone, and wherein at least 75% of the particles of dexamethasone have a diameter of less than about 20 .mu.m.
7. The method of claim 1, wherein the ratio of hydrophilic end PLGA to hydrophobic end PLGA in the bioerodible implant is 3:1 by weight.
8. The method of claim 1, wherein the active agent is selected from the group consisting of ace-inhibitors, endogenous cytokines, agents that influence basement membrane, agents that influence the growth of endothelial cells, adrenergic agonists, adrenergic blockers, cholinergic agonists, cholinergic blockers, aldose reductase inhibitors, analgesics, anesthetics, antiallergics, anti-inflammatory agents, antihypertensives, pressors, antibacterials, antivirals, antifungals, antiprotozoals, anti-infectives, antitumor agents, antimetabolites, and antiangiogenic agents.
9. The method of claim 8, wherein the active agent is an anti-inflammatory agent selected from the group consisting of steroidal anti-inflammatory agents and non-steroidal anti-inflammatory agents.
10. The method of claim 9, wherein the active agent is a non-steroidal anti-inflammatory agent selected from the group consisting of aspirin, diclofenac, flurbiprofen, ibuprofen, ketorolac, naproxen, and suprofen.
11. The method of claim 8, wherein the active agent is a steroidal anti-inflammatory agent selected from the group consisting of 21-acetoxypregnenolone, alclometasone, algestone, amcinonide, beclomethasone, betamethasone, budesonide, chloroprednisone, clobetasol, clobetasone, clocortolone, cloprednol, corticosterone, cortisone, cortivazol, deflazacort, desonide, desoximetasone, dexamethasone, diflorasone, diflucortolone, difluprednate, enoxolone, fluazacort, flucloronide, flumethasone, flunisolide, fluocinolone acetonide, fluocinonide, fluocortin butyl, fluocortolone, fluorometholone, fluperolone acetate, fluprednidene acetate, fluprednisolone, flurandrenolide, fluticasone propionate, formocortal, halcinonide, halobetasol propionate, halometasone, halopredone acetate, hydrocortamate, hydrocortisone, loteprednol etabonate, mazipredone, medrysone, meprednisone, methylprednisolone, mometasone furoate, paramethasone, prednicarbate, prednisolone, prednisolone 25-diethylamino-acetate, prednisolone sodium phosphate, prednisone, prednival, prednylidene, rimexolone, tixocortol, triamcinolone, triamcinolone acetonide, triamcinolone benetonide, triamcinolone hexacetonide, and fluocinolone.
12. The method of claim 11, wherein the steroidal anti-inflammatory agent constitutes from about 10% to about 90% by weight of the implant.
13. The method of claim 11, wherein the medical condition of the eye is uveitis, vascular occlusion, or macular edema.