Controlled-release cns modulating compositions and methods for the treatment of otic disorders

Abstract

Disclosed herein are compositions and methods for the treatment of otic disorders with CNS modulating agent compositions and compositions administered locally to an individual afflicted with an otic disorder, through direct application of these compositions and compositions onto or via perfusion into the targeted auris structure(s).

1 .- 20 . (canceled) 
     
     
         21 . An otic composition for intratympanic administration comprising:
 a) an active agent; and   b) from about 10% to about 40% by weight of Poloxamer 407;
 wherein the active agent is from about 2% to about 15% by weight of valproic acid or sodium valproate, and 
 wherein the composition is a suspension and wherein the composition provides sustained release of the active agent into the ear after intratympanic administration. 
   
     
     
         22 . The otic composition of  claim 21 , wherein the composition comprises from about 14% to about 21% by weight of Poloxamer 407. 
     
     
         23 . The otic composition of  claim 21 , wherein the composition comprises from about 14% to about 17% by weight of Poloxamer 407. 
     
     
         24 . The otic composition of  claim 21 , wherein the composition comprises from about 6% to about 10% by weight of valproic acid or sodium valproate. 
     
     
         25 . The otic composition of  claim 21 , wherein the active agent is not in the form of nanoparticles, microspheres or microparticles. 
     
     
         26 . The otic composition of  claim 21 , wherein the composition has a pH between about 5.5 and about 9.0. 
     
     
         27 . The otic composition of  claim 21 , wherein the composition has a gelation temperature from about 19° C. to about 37° C. 
     
     
         28 . The otic composition of  claim 21 , wherein the composition has a gelation temperature from about 19° C. to about 30° C. 
     
     
         29 . The otic composition of  claim 21 , wherein the composition provides sustained release of the active agent into the ear for at least 3 days after intratympanic administration. 
     
     
         30 . The otic composition of  claim 21 , wherein the composition provides sustained release of the active agent into the ear for at least 5 days after intratympanic administration. 
     
     
         31 . The otic composition of  claim 21 , wherein the composition provides sustained release of the active agent into the ear for at least 7 days after intratympanic administration. 
     
     
         32 . The otic composition of  claim 21 , wherein the composition comprises DMSO. 
     
     
         33 . The otic composition of  claim 21 , wherein the composition is injectable through a 18-31 gauge needle. 
     
     
         34 . The otic composition of  claim 21 , wherein the active agent reduces hair cell damage. 
     
     
         35 . The otic composition of  claim 21 , wherein the active agent has a trophic effect. 
     
     
         36 . A method of treating an otic disease or condition comprising administering to an individual in need thereof an intratympanic composition comprising:
 a) an active agent; and   b) from about 10% to about 40% by weight of a polyoxyethylene-polyoxypropylene triblock copolymer;
 wherein the active agent is from about 2% to about 15% by weight of valproic acid or sodium valproate, and 
 wherein the composition is a suspension and wherein the composition provides sustained release of the active agent into the ear after intratympanic administration. 
   
     
     
         37 . The method of  claim 36 , wherein the composition comprises from about 14% to about 17% by weight of the polyoxyethylene-polyoxypropylene triblock copolymer. 
     
     
         38 . The otic composition of  claim 21 , wherein the composition comprises from about 6% to about 10% by weight of valproic acid or sodium valproate. 
     
     
         39 . The method of  claim 36 , wherein the composition has a gelation temperature from about 19° C. to about 30° C. 
     
     
         40 . The method of  claim 36 , wherein the otic disease or condition is hearing loss.