Channel modulators

Abstract

The inventions relate to compositions and articles of manufacture comprising connexin modulators, pannexin modulators, gap junction modulators, hemichannel modulators, and pannexin channel modulators and their use, alone or in combination, in treating ocular and other disorders.

What is claimed is: 
     
         1 - 73 . (canceled) 
     
     
         74 . A method for treating a subject for an ocular chronic wound, comprising topically administering to the eye of said subject a composition comprising an pharmaceutically acceptable carrier and from about 0.6 to about 60 mg/mL of a connexin 43 antisense oligonucleotide having the sequence 5′ GTA ATT GCG GCA AGA AGA ATT GTT TCT GTC 3′ (SEQ ID NO: 1). 
     
     
         75 . The method according to  claim 74 , wherein the ocular chronic wound is an ocular ulcer. 
     
     
         76 . The method according to  claim 74 , wherein the ocular chronic wound is an ocular persistent epithelial defect. 
     
     
         77 . The method according to  claim 74 , wherein the ocular chronic wound is a corneal persistent epithelial defect. 
     
     
         78 . The method according to  claim 74 , wherein the connexin 43 antisense oligonucleotide is an unmodified oligonucleotide. 
     
     
         79 . The method according to  claim 74 , wherein the connexin 43 antisense oligonucleotide is a modified oligonucleotide. 
     
     
         80 . The method according to  claim 79 , wherein one or more nucleotide linkages and/or one or more nucleotide sugar moieties in the connexin 43 antisense oligonucleotide are modified. 
     
     
         81 . The method according to  claim 74 , wherein the composition contains about 0.6 mg/mL of said connexin 43 antisense oligonucleotide. 
     
     
         82 . The method according to  claim 74 , wherein the composition comprises a reverse-thermosetting gel. 
     
     
         83 . The method according to  claim 82 , wherein the reverse-thermosetting gel is a nonionic polyoxyethylene-polyoxypropylene copolymer gel. 
     
     
         84 . The method according to  claim 83 , wherein the nonionic polyoxyethylene-polyoxypropylene copolymer is a pluronic gel. 
     
     
         85 . The method according to  claim 84 , wherein the pluronic gel comprises poloxamer 407. 
     
     
         86 . The method according to  claim 82 , wherein the composition further comprises a buffer. 
     
     
         87 . The method according to  claim 74 , wherein the composition comprises a transfection agent. 
     
     
         88 . The method according to  claim 74 , wherein the composition comprises a surfactant. 
     
     
         89 . The method according to  claim 74 , wherein the composition comprises a preservative. 
     
     
         90 . The method according to  claim 74 , wherein the composition comprises a salt. 
     
     
         91 . The method according to  claim 74 , wherein the composition comprises a compound selected from the group consisting of propylene glycol, dimethyl isosorbide, phosphate buffered saline, water, isotonic water, deionized water, a monofunctional alcohol, a symmetrical alcohol, a carboxycellulose, a collagen, tropocollagen, a hyaluronic acid, a derived-hyaluronic acid, a hyaluronan and an oil. 
     
     
         92 . The method according to  claim 74 , wherein the composition comprises a compound selected from the group consisting of hydroxymethylcellulose, hydroxyethylcellulose, carboxymethylcellulose, and hydroxypropylmethylcellulose. 
     
     
         93 . The method according to  claim 74 , wherein the composition is a slow or delayed release preparation. 
     
     
         94 . The method according to  claim 74 , wherein the composition is formulated for delivery under a contact lens. 
     
     
         95 . The method according to  claim 74 , wherein the composition is contained within, delivered by, or attached to a contact lens placed on the eye of said subject. 
     
     
         96 . The method according to  claim 74 , wherein the composition is delivered in conjunction with a contact lens that is placed on the eye of said subject. 
     
     
         97 . A kit including a pharmaceutical composition comprising an ophthalmologically acceptable carrier and from about 0.6 to about 60 mg/mL of a connexin 43 antisense oligonucleotide having the sequence 5′ GTA ATT GCG GCA AGA AGA ATT GTT TCT GTC 3′ (SEQ ID NO: 1) and instructions for use in treating an ocular persistent epithelial defect. 
     
     
         98 . The kit according to  claim 97 , further comprising a contact lens.