Anterior segment drug delivery

Abstract

A therapeutic system comprises an ocular insert placed on a region outside an optical zone of an eye. The ocular insert comprises two structures: a first skeletal structure and a second cushioning structure. The first structure functions as a skeletal frame which maintains positioning of the implant along the anterior portion of the eye and provides support to the second, cushioning structure. This first structure maintains the attachment of the therapeutic system to the anterior portion of the eye for at least thirty days. In some embodiments the first structure remains a constant size and shape, e.g. a ring shape, a ring with haptics, or a curvilinear ring that is confined to and restrainingly engages the inferior and superior conjunctival fornices so as to retain the implant within the tear fluid and/or against the tissues of the eye.

1 - 23 . (canceled) 
     
     
         24 . An ocular insert for use in an eye, the eye having upper and lower lids, the insert disposable along an anterior eye surface of the eye outside the optical zone, the insert comprising:
 an inner structure comprising a loop of suture having a circumferential length, the inner structure configured to conform to a radius of curvature of the eye;   an outer structure supported by the inner structure, the outer structure comprising one or more tubular segments of a drug delivery matrix surrounding the circumferential length of the suture, the outer structure forming an anterior surface, a posterior surface, an inner edge, and an outer edge of the ocular insert along the circumferential length; and   at least one drug dispersed in the drug delivery matrix so as to release a safe and therapeutically effective quantity of the drug to the eye for each of a plurality of days.   
     
     
         25 . The ocular insert of  claim 24 , wherein the plurality of days comprises at least 30 days, at least 60 days, at least 90 days, or up to about 180 days. 
     
     
         26 . The ocular insert of  claim 24 , wherein the drug comprises one or more members selected from the group consisting of: steroids, anti-inflammatories, antibiotics, glaucoma treatment compounds, antihistamines, and dry eye medication. 
     
     
         27 . The ocular insert of  claim 24 , wherein the drug is hydrophilic, and wherein the drug is dispersed in a hydrophilic polymer. 
     
     
         28 . The ocular insert of  claim 24 , wherein the drug is hydrophobic, and wherein the insert comprises surfactants to increase the drug solubility. 
     
     
         29 . The ocular insert of  claim 24 , wherein the at least one drug is hydrophobic, and wherein the insert comprises an elution rate decrease material, the elution rate decrease material comprising a coating over the at least one drug, a component of the drug delivery matrix, and/or a coating on the drug delivery matrix. 
     
     
         30 . The ocular insert of  claim 24 , wherein the at least one drug comprises one or more member selected from the group consisting of:
 a steroid selected from the group consisting of at least one of glucocorticoids, aprogestins, amineralocorticoids, corticosteroids, cortisone, hydrocortisone, prednisone, prednisolone, methylprednisone, triamcinolone, fluoromethalone, dexamethasone, medrysone, betamethasone, loteprednol, fluocinolone, flumethasone, rimexolone mometasone, androgens, testosterone, methyltestosterone, and danazol;   a non-steroidal anti-inflammatory (NSAID) selected from the group consisting of at least one of piroxicam, aspirin, salsalate, diflunisal, ibuprofen, ketoprofen, nabumetone, piroxicam, naproxen, diclofenac, indomethacin, sulindac, tolmetin, etodolac, ketorolac, oxaprozin, and celecoxib;   an antibiotic selected from the group consisting of at least one of amoxicillin, penicillin, sulfa drugs, erythromycin, streptomycin, tetracycline, clarithromycin, terconazole, azithromycin, bacitracin, ciprofloxacin, evofloxacin, ofloxacin, levofloxacin, moxifloxacin, gatifloxacin, aminoglycosides, tobramycin, gentamicin, polymyxin B combinations, wherein the polymyxin B combinations are selected from the group consisting of polymyxin B/trimethoprim, polymyxin B/bacitracin, and polymyxin B/neomycin/gramicidin;   a glaucoma treatment medication selected from the group consisting of at least one of beta-blockers, mitotics, carbonic anhydrase inhibitors, prostaglandins, prostaglandin analogs, seretonergics, muscarinics, dopaminergic agonists, and adrenergic agonists,   wherein the beta-blockers are selected from the group consisting of timolol, betaxolol, levobetaxolol, and carteolol,   wherein the mitotics are selected from the group consisting of pilocarpine,   wherein the carbonic anhydrase inhibitors are selected from the group consisting of brinzolamide, and dorzolamide,   wherein the prostaglandin analogs are selected from the group consisting of travoprost, bimatoprost, and latanoprost, and   wherein the adrenergic agonists are selected from the group consisting of apraclonidine, and brimonidine;   an antihistamine and mast cell stabilizer selected from the group consisting of at least one of ketorolac tromethamine, ketotifen fumarate, loteprednol, epinastine HCl, emedastine difumarate, azelastine hydrochloride, olopatadine hydrochloride;   a chronic care anti-allergenic product selected from the group consisting of at least one of pemirolast potassium, nedocromil sodium, lodoxamide tromethamine, and cromolyn sodium; and   a dry eye medication selected from the group consisting of cyclosporine; and   an anesthetic.   
     
     
         31 . The ocular insert of  claim 24 , wherein the inner structure is formed of a synthetic suture material. 
     
     
         32 . The ocular insert of  claim 31 , wherein the synthetic suture material is polypropylene or nylon. 
     
     
         33 . The ocular insert of  claim 24 , wherein the inner structure is selected from the group consisting of nylon, polymethyl methacrylate (PMMA), polycarbonate, polyethylene terepthalate, and polypropylene. 
     
     
         34 . The ocular insert of  claim 24 , wherein the inner structure is a shape memory material. 
     
     
         35 . The ocular insert of  claim 34 , wherein the shape memory material is selected from the group consisting of shape memory polyurethanes, crosslinked trans-polyoctylene rubber, polynorbornene polymers, nitinol, polyethylene, PMMA, polyurethane, cross-linked polyethylene, cross-linked polyisoprene, polycycloocetene, polycaprolactone, copolymers of (oligo)caprolactone, poly(L-lactic acid) (PLLA), poly(L-co-D,L lactide (PL/DLA) copolymers, and PLLA poly(glycolic acid) (PGA) copolymers. 
     
     
         36 . The ocular insert of  claim 24 , wherein the inner structure has a diameter sized to fit on an anterior surface of the eye outside the optical zone of the cornea. 
     
     
         37 . The ocular insert of  claim 36 , wherein the diameter is at least 8 mm. 
     
     
         38 . The ocular insert of  claim 24 , wherein the insert is sized to fit on the sclera, fornix, or cul-de-sac of the eye. 
     
     
         39 . The ocular insert of  claim 24 , wherein the drug delivery matrix is a non-biodegradable material. 
     
     
         40 . The ocular insert of  claim 24 , wherein the drug delivery matrix is formed of a silicone polymer. 
     
     
         41 . The ocular insert of  claim 24 , wherein the outer edges and/or inner edges of the drug delivery matrix are shaped to inhibit friction between the outer edges and/or inner edges and a lid of the eye. 
     
     
         42 . The ocular insert of  claim 24 , wherein the anterior surface and/or posterior surface of the drug delivery matrix are shaped to the radius of the curvature of the eye. 
     
     
         43 . The ocular insert of  claim 24 , wherein the outer edges and/or inner edges of the drug delivery matrix are rounded in cross-section. 
     
     
         44 . The ocular insert of  claim 24 , wherein the outer edges and/or inner edges of the drug delivery matrix are beveled in cross-section. 
     
     
         45 . The ocular insert of  claim 24 , wherein the outer edges and/or inner edges of the drug delivery matrix are tapered in cross-section. 
     
     
         46 . The ocular insert of  claim 24 , wherein the one or more tubular segments of the drug delivery matrix surrounds discrete portions of the circumferential length. 
     
     
         47 . The ocular insert of  claim 24 , wherein a material of the inner structure and the drug delivery matrix have different durometers. 
     
     
         48 . The ocular insert of  claim 24 , wherein the insert is used to treat a condition selected from the group consisting of dry eye, glaucoma, allergies, infections, acne rosacea keratitis, cyclitis, blepharitis, diabetic retinopathy, age related macular degeneration, and amblyopia. 
     
     
         49 . A method of implanting the ocular insert of  claim 24 , the method comprising:
 manually pinching the ocular insert at first and second positions around a circumference of the insert forming a first folded portion and a second folded portion;   manually positioning the first folded portion under at least one of a lower eyelid or an upper eyelid;   manually positioning the second folded portion under the other of the lower eyelid or the upper eyelid; and   encircling with the ocular insert an anterior surface of the eye outside the optical zone of the cornea.   
     
     
         50 . A method of treating an ocular condition with the ocular insert of  claim 24 , the method comprising:
 inserting the ocular insert on an anterior surface of the eye outside the optical zone of the cornea;   releasing the therapeutically effective quantity of the drug for the plurality of days; and   removing the ocular insert from the anterior surface of the eye after the plurality of days.   
     
     
         51 . An ocular insert for use in an eye, the eye having an upper lid and a lower lid, the insert disposable along an anterior eye surface of the eye outside the optical zone, the insert comprising:
 an inner structure comprising a loop of suture having a circumferential length, the inner structure configured to conform to a radius of curvature of the eye;   an outer structure supported by the inner structure, the outer structure comprising one or more tubular segments of a drug delivery matrix disposed along the circumferential length of the suture, the delivery matrix forming an anterior surface, a posterior surface, an inner edge, and an outer edge of the ocular insert along the circumferential length; and   at least one drug dispersed in the drug delivery matrix so as to release a safe and therapeutically effective quantity of the drug to the eye for each of a plurality of days.