Lfa-1 inhibitor formulations

Abstract

The present invention provides formulations, methods and kits for the treatment of dry eye diseases. In particular, stabilized pharmaceutical compositions comprising the compound of Formula 1 are described herein for a variety of uses including the treatment of dry eye syndrome. In one aspect, methods and ingredients for improving the stability of compositions of the compound of Formula 1 are described.

1 .- 52 . (canceled) 
     
     
         53 . A method of treating disease in a subject in need thereof comprising the step of administering an effective amount of a composition to said subject, wherein the composition comprises a compound of Formula 1: 
       
         
           
           
               
               
           
         
         or a salt thereof,
 a pharmaceutically acceptable carrier, and 
 a thiosulfate salt, 
 
         wherein the composition has less than about 1% of total degradation products of the compound of Formula 1 when stored at a temperature of about 40° C. for a period of at least one month. 
       
     
     
         54 . The method of  claim 53 , wherein the disease is an eye disease. 
     
     
         55 . The method of  claim 60 , wherein the dry eye disease is secondary to presumed ocular surface inflammation. 
     
     
         56 . The method of  claim 54 , wherein said administering comprises topical administration to the eye. 
     
     
         57 . The method of  claim 56 , wherein said composition is administered in the form of eye drops. 
     
     
         58 .- 59 . (canceled) 
     
     
         60 . The method of  claim 54 , wherein the eye disease is dry eye syndrome. 
     
     
         61 . The method of  claim 53 , wherein the composition comprises thiosulfate salt in an amount of about 0.01% to about 0.5% w/v. 
     
     
         62 . The method of  claim 61 , wherein the thiosulfate salt is present in an amount of about 0.3% w/v. 
     
     
         63 . The method of  claim 53 , wherein the thiosulfate salt in the composition is sodium thiosulfate. 
     
     
         64 . The method of  claim 53 , wherein the composition is buffered to a pH of about 6.0 to about 8.5. 
     
     
         65 . The method of  claim 53 , wherein the compound of Formula 1 is present in the composition in an amount of about 1% to about 5% w/v. 
     
     
         66 . The method of  claim 65 , wherein the compound of Formula 1 is present in an amount of about 5% w/v. 
     
     
         67 . The method of  claim 53 , wherein the composition exhibits less than about 1% of total degradation products of the compound of Formula 1 upon storage at a temperature of about 40° C. for a time period selected from the group consisting of 2 months, 3 months, 4 months, 5 months, and 6 months. 
     
     
         68 . The method of  claim 53 , wherein the composition further comprises a sparged nitrogen gas. 
     
     
         69 . The method of  claim 53 , wherein the composition comprises:
 about 5% w/v of the compound of Formula 1;   about 0.3% w/v thiosulfate salt;   sodium chloride; and   sodium phosphate, and   
       wherein the composition has a pH of about 7.0 to about 8.0. 
     
     
         70 . The method of  claim 69 , wherein the sodium phosphate is dibasic sodium phosphate. 
     
     
         71 . A method of treating a disease in a subject in need thereof, comprising the step of administering an effective amount of a composition to said subject, wherein the composition comprises:
 4 to 10 w/v % compound of Formula 1:   
       
         
           
           
               
               
           
         
       
       or a salt thereof; and 
       0.2 to 0.4% antioxidant, the antioxidant being sodium thiosulfate; 
       wherein the composition is an aqueous solution with the compound of Formula 1 dissolved therein, and 
       wherein the composition is suitable for topical administration to the eye, and wherein the disease is an eye disease. 
     
     
         72 . The method of  claim 71 , wherein the composition comprises:
 about 5 w/v % compound of Formula 1 or a salt thereof;   about 0.3% w/v of sodium thiosulfate;   sodium phosphate for buffering the compositions at a pH of 6.0 to 8.0; and   sodium chloride for providing isotonicity to the composition.   
     
     
         73 . The method of  claim 72 , wherein the composition is buffered to a pH of about 7.5. 
     
     
         74 . The method of  claim 71 , wherein the eye disease is dry eye disease. 
     
     
         75 . The method of  claim 74 , wherein the dry eye disease is secondary to presumed ocular surface inflammation.