Therapeutic Compositions For Treatment Of Inflammation Of Ocular And Adnexal Tissues

Abstract

The present invention comprises a composition with means to inhibit the function of the inflammatory cytokine IL-1 and methods for using this composition to treat inflammatory disease of ocular and adnexal tissues by topical administration. The present invention also discloses devices for delivering this composition to target tissues.

What is claimed is: 
     
         1 . A method for inhibiting or reducing the severity of an inflammatory disorder affecting the ocular and adnexal tissues, comprising locally administering to ocular and adnexal tissue of a subject a therapeutically effective amount of a composition that inhibits an activity of an inflammatory interleukin-1 cytokine. 
     
     
         2 . The method of  claim 1 , wherein the therapeutically effective amount of a composition is administered when the inflammatory disorder of the subject is improved after administration of the composition compared to the inflammatory disorder in the subject prior to treatment, wherein the improvement is determined using one or more tests selected from the group consisting of meibomian gland secretion quality, meibomian gland occlusion, tear break-up time, corneal and conjunctival staining, Schirmer test with anesthesia, Schirmer test without anesthesia, or ocular surface disease index (OSDI) score. 
     
     
         3 . The method of  claim 2 , wherein a therapeutically effective amount of the composition is determined
 a. by using meibomian gland secretion quality, wherein a mean change in meibomian gland secretion quality from untreated (0-3 scale) of greater than 1 unit by 12 weeks of treatment indicates a therapeutically effective amount was administered; or   b. by using corneal and conjunctival staining, wherein a mean change in average score from untreated (0-5 scale) for corneal and conjunctival staining of greater than 1 unit by 12 weeks after initiation of treatment indicates a therapeutically effective amount was administered.   
     
     
         4 . The method of  claim 1 , wherein the activity comprises binding of an inflammatory IL-1 cytokine to an IL-1 receptor. 
     
     
         5 . The method of  claim 1 , further comprising identifying a subject characterized as suffering from an inflammatory disorder affecting the ocular and adnexal tissues. 
     
     
         6 . The method of  claim 3 , wherein identifying a subject comprises detection of a sign or symptom selected from the group consisting of epithelial overexpression of an inflammatory cytokine, vascular hyperplasia or thickening of lid margin, neovascularization of lid margin or corneal periphery, increase of leukocytes at an ocular surface, or overexpression of a matrix metalloprotease at an ocular surface and wherein the method inhibits or reduces the severity of at least one of the signs or symptoms. 
     
     
         7 . The method of  claim 1 , wherein the inflammatory disorder is characterized as infectious blepharitis, non-infectious blepharitis, meibomian gland dysfunction, dry eye, or Sjogren syndrome. 
     
     
         8 . The method of  claim 1 , wherein the method further comprises administration of an antibiotic compound. 
     
     
         9 . The method of  claim 1 , wherein the composition that inhibits binding of an inflammatory IL-1 cytokine to an IL-1 receptor comprises an amino acid sequence of SEQ ID NO: 15 or SEQ ID NO: 16. 
     
     
         10 . The method of claim, 1 wherein the composition is present in a concentration of 0.1-10% (mg/ml). 
     
     
         11 . The method of  claim 1 , wherein the form of said composition is a solid, a paste, an ointment, a gel, a liquid, an aerosol, a mist, a polymer, a film, an emulsion, or a suspension. 
     
     
         12 . The method of  claim 1 , wherein the composition is administered topically. 
     
     
         13 . The method of  claim 1 , wherein the method does not comprise systemic administration or substantial dissemination to non-ocular tissue. 
     
     
         14 . The method of  claim 13 , wherein seven hours after a single administration the composition is at a serum concentration less than 1200 ng/ml. 
     
     
         15 . The method of  claim 1 , wherein the composition further comprises a compound selected from the group consisting of a physiological acceptable salt, poloxamer analogs with carbopol, carbopol/HPMC, carbopol-methyl cellulose, carboxymethylcellulose (CMC), hyaluronic acid, cyclodextrin, and petroleum. 
     
     
         16 . A formulation comprising a therapeutically effective amount of a composition that inhibits an activity of an inflammatory interleukin-1 cytokine, the formulation being in the form of a solid, a paste, a liquid, an ointment, a gel, an aerosol, a mist, a polymer, a film, an emulsion, or a suspension, and wherein the composition is present at a concentration of 0.1-10% (mg/ml). 
     
     
         17 . The formulation of  claim 16 , wherein said composition comprises a polypeptide comprising the amino acid sequence of SEQ ID NO: 15 or SEQ ID NO: 16. 
     
     
         18 . A method for inhibiting or reducing the severity of an ocular inflammatory disorder, comprising locally administering to the ocular or adnexal tissue of a subject a therapeutically effective amount of a composition that can inhibit transcription, transcript stability, translation, modification, localization, secretion, or function of a polynucleotide or polypeptide encoding an inflammatory interleukin-1 cytokine or an IL-1 receptor. 
     
     
         19 . The method of  claim 18 , wherein the composition comprises a polynucleotide, a polypeptide, an antibody, or a small molecule. 
     
     
         20 . The method of  claim 18 , wherein said composition is administered topically. 
     
     
         21 . A device comprising a polymer and a bioactive composition incorporated into or onto said polymer, wherein said bioactive composition inhibits an activity of an inflammatory interleukin-1 cytokine, and wherein said device is incorporated into or onto an ocular or adnexal tissue. 
     
     
         22 . The device of  claim 21 , wherein the device is a contact lens. 
     
     
         23 . The method of  claim 1 , wherein the method comprises administration of a composition that can inhibit binding of an inflammatory IL-1 cytokine to an IL-1 receptor and a second composition comprising one or more inflammatory antagonist(s). 
     
     
         24 . The method of  claim 23 , wherein the second composition can inhibit a tumor necrosis factor alpha (TNFα), one or more interleukin cytokines, one or more member(s) of the vascular epithelial growth factor (VEGF) family, interferon-gamma, or one or more chemokines and their receptors, or is an immunosuppressant.