Ocular applications of silk-based products

Abstract

The embodiments disclosed and embraced by the present invention include silk-based products useful in the treatment, diagnosis, palliation, and/or amelioration of ocular diseases or conditions of the eye including those of the structures of the eye and surrounding tissue. Such silk-based products may effect beneficial outcomes alone or in combination with therapeutic modalities, compounds or medicaments.

1 . A silk-based product (SBP) comprising processed silk and an ocular therapeutic agent wherein the SBP comprises from about 0.1% to about 98% (w/w) of the ocular therapeutic agent. 
     
     
         2 . The SBP of  claim 1 , wherein the SBP is in the shape of a rod. 
     
     
         3 - 6 . (canceled) 
     
     
         7 . The SBP of  claim 1 , wherein the SBP comprises a ratio of ocular therapeutic agent concentration to processed silk concentration of from about 0.01 to about 4.2. 
     
     
         8 - 9 . (canceled) 
     
     
         10 . The SBP of  claim 1  comprising at least one excipient, wherein the at least one excipient is present at a concentration of from about 0.01% (w/w) to about 20% (w/w). 
     
     
         11 . The SBP of  claim 10 , wherein the at least one excipient selected from the group consisting of lactose, sorbitol, sucrose, mannitol, lactose USP, Starch 1500, microcrystalline cellulose, Avicel, phosphate salts, sodium chloride, hydrochloric acid, polysorbate 80, potassium phosphate monobasic, potassium phosphate dibasic, sodium phosphate dibasic, sodium phosphate monobasic, phosphate buffer, phosphate buffered saline, sodium hydroxide, dibasic calcium phosphate dehydrate, tartaric acid, citric acid, fumaric acid, succinic acid, malic acid, polyvinylpyrrolidone, copolymers of vinylpyrrolidone and vinylacetate, hydroxypropylcellulose, hydroxyethylcellulose, hydroxypropylmethylcellulose, polyvinyl alcohol, polyethylene glycol, acacia, and sodium carboxymethylcellulose. 
     
     
         12 . The SBP of  claim 11 , wherein one of the at least one excipient is sucrose. 
     
     
         13 - 14 . (canceled) 
     
     
         15 . The SBP of  claim 1 , wherein the SBP is in the shape of a rod and wherein the rod has a diameter of from about 0.1 mm to about 1.5 mm. 
     
     
         16 . (canceled) 
     
     
         17 . The SBP of  claim 1 , wherein the SBP comprises a hydrogel. 
     
     
         18 . (canceled) 
     
     
         19 . The SBP of  claim 17 , wherein the SBP comprises at least one excipient, and wherein the at least one excipient is selected from the group consisting of sorbitol, triethylamine, 2-pyrrolidone, alpha-cyclodextrin, benzyl alcohol, beta-cyclodextrin, dimethyl sulfoxide, dimethylacetamide (DMA), dimethylformamide, ethanol, gamma-cyclodextrin, glycerol, glycerol formal, hydroxypropyl beta-cyclodextrin, kolliphor 124, kolliphor 181, kolliphor 188, kolliphor 407, kolliphor EL (cremaphor EL), cremaphor RH 40, cremophor RH 60, dalpha-tocopherol, PEG 1000 succinate, polysorbate 20, polysorbate 80, solutol HS 15, sorbitan monooleate, poloxamer-407, poloxamer-188, Labrafil M-1944CS, Labrafil M-2125CS, Labrasol, Gellucire 44/14, Softigen 767, mono- and di-fatty acid esters of PEG 300, PEG 400, or PEG 1750, kolliphor RH60, N-methyl-2-pyrrolidone, castor oil, corn oil, cottonseed oil, olive oil, peanut oil, peppermint oil, safflower oil, sesame oil, soybean oil, hydrogenated vegetable oils, hydrogenated soybean oil, medium chain triglycerides of coconut oil, medium chain triglycerides of palm seed oil, beeswax, d-alpha-tocopherol, oleic acid, medium-chain mono-glycerides, medium-chain di-glycerides, alpha-cyclodextrin, betacyclodextrin, hydroxypropyl-beta-cyclodextrin, sulfo-butylether-beta-cyclodextrin, hydrogenated soy phosphatidylcholine, distearoylphosphatidylglycerol, L-alphadimyristoylphosphatidylcholine, L-alpha-dimyristoylphosphatidylglycerol, PEG 300, PEG 300 caprylic/capric glycerides (Softigen 767), PEG 300 linoleic glycerides (Labrafil M-2125CS), PEG 300 oleic glycerides (Labrafil M-1944CS), PEG 400, PEG 400 caprylic/capric glycerides (Labrasol), polyoxyl 40 stearate (PEG 1750 monosterate), polyoxyl 8 stearate (PEG 400 monosterate), polyvinyl pyrrolidone, propylene carbonate, propylene glycol, solutol HS15, sorbitan monooleate (Span 20), sulfobutylether-beta-cyclodextrin, transcutol, triacetin, 1-dodecylazacyclo-heptan-2-one, caprolactam, castor oil, cottonseed oil, ethyl acetate, medium chain triglycerides, methyl acetate, oleic acid, safflower oil, sesame oil, soybean oil, tetrahydrofuran, glycerin, and PEG 4 kDa. 
     
     
         20 . The SBP of  claim 19 , wherein the at least one excipient is poloxamer-188. 
     
     
         21 . The SBP  claim 19 , wherein the at least one excipient is PEG 4 kDa. 
     
     
         22 . The SBP  claim 19 , wherein the at least one excipient is glycerol. 
     
     
         23 . The SBP  claim 1 , wherein the processed silk comprises silk fibroin, and wherein the silk fibroin is present in the SBP at a concentration of from about 0.1% (w/v) to about 30% (w/v). 
     
     
         24 - 25 . (canceled) 
     
     
         26 . The SBP  claim 1 , wherein the SBP has an osmolarity which is from about 275 mOsm to about 285 mOsm. 
     
     
         27 - 32 . (canceled) 
     
     
         33 . The SBP of  claim 1 , wherein the ocular therapeutic agent comprises a non-steroidal anti-inflammatory drug (NSAID). 
     
     
         34 . The SBP of  claim 33 , wherein the NSAID comprises one or more of aspirin, carprofen, celecoxib, deracoxib, diclofenac, diflunisal, etodolac, fenoprofen, firocoxib, flurbirofen, ibuprofen, indomethacin, ketoprofen, ketorolac, mefenamic acid, meloxicam, nabumetone, naproxen, oxaprozin, piroxicam, robenacoxib, salsalate, sulindac, and tolmetin. 
     
     
         35 . The SBP of  claim 34 , wherein the NSAID is celecoxib. 
     
     
         36 - 37 . (canceled) 
     
     
         38 . A pharmaceutical composition, wherein the pharmaceutical composition comprises the SBP of  claim 1  and at least one excipient, wherein the SBP is formulated for intraocular administration. 
     
     
         39 . The pharmaceutical composition of  claim 38 , wherein the SBP is formulated for one or more of intravitreal administration, intraretinal administration, intracorneal administration, intrascleral administration, punctal administration, administration to the anterior sub-Tenon's, suprachoroidal administration, administration to the posterior sub-Tenon's, subretinal administration, administration to the fornix, administration to the lens, and intra-aqueous humor administration. 
     
     
         40 - 45 . (canceled) 
     
     
         46 . A method of treating a subject comprising contacting the subject with the pharmaceutical composition of  claim 38 . 
     
     
         47 . The method of  claim 46 , wherein the subject comprises an ocular indication. 
     
     
         48 . (canceled) 
     
     
         49 . The method of  claim 47 , wherein the ocular indication comprises one or more of an infection, refractive errors, age related macular degeneration, cystoid macular edema, cataracts, diabetic retinopathy (proliferative and non-proliferative), glaucoma, amblyopia, strabismus, color blindness, cytomegalovirus retinitis, keratoconus, diabetic macular edema (proliferative and non-proliferative), low vision, ocular hypertension, retinal detachment, eyelid twitching, inflammation, uveitis, bulging eyes, dry eye disease, floaters, xerophthalmia, diplopia, Graves' disease, night blindness, eye strain, red eyes, nystagmus, presbyopia, excess tearing, retinal disorder, conjunctivitis, cancer, corneal ulcer, corneal abrasion, snow blindness, scleritis, keratitis, Thygeson's superficial punctate keratopathy, corneal neovascularization, Fuch's dystrophy, keratoconjunctivitis sicca, iritis, chorioretinal inflammation (e.g. chorioretinitis, choroiditis, retinitis, retinochoroiditis, pars planitis, Harada's disease, aniridia, macular scars, solar retinopathy, choroidal degeneration, choroidal dystrophy, choroideremia, gyrate atrophy, choroidal hemorrhage, choroidal detachment, retinoschisis, hypertensive retinopathy, Bull's eye maculopathy, epiretinal membrane, peripheral retinal degeneration, hereditary retinal dystrophy, retinitis pigmentosa, retinal hemorrhage, retinal vein occlusion, and separation of retinal layers. 
     
     
         50 - 51 . (canceled) 
     
     
         52 . The method of  claim 47 , wherein the pharmaceutical composition is administered to the subject via intravitreal administration. 
     
     
         53 - 57 . (canceled) 
     
     
         58 . The method of  claim 46 , wherein contacting the subject with the pharmaceutical composition results in a concentration of the ocular therapeutic agent in an eye of the subject of from about 0.01 ng/mL to about 60,500 ng/mL. 
     
     
         59 - 66 . (canceled) 
     
     
         67 . The method of  claim 58 , wherein the ocular therapeutic agent is detectable in one or more components of the eye for at least 3 months. 
     
     
         68 - 77 . (canceled) 
     
     
         78 . The method of  claim 67 , wherein the eye component is selected from the group consisting of the retina, the vitreous humor, and/or choroid. 
     
     
         79 - 105 . (canceled)