Controlled release compositions for modulating free-radical induced damage and methods of use thereof

Abstract

Disclosed herein are compositions and methods for the treatment of otic diseases or conditions with free-radical modulating agent compositions and formulations administered locally to an individual afflicted with an otic disease or condition, through direct application of these compositions and formulations onto or via perfusion into the targeted auris structure(s).

1 - 20 . (canceled) 
     
     
         21 . An intratympanic composition for use in the treatment of an otic disease or condition, the intratympanic composition comprising
 a micronized NMDA receptor antagonist, or pharmaceutically acceptable salt thereof, wherein the NMDA receptor antagonist is ketamine; and   an auris acceptable gel,   wherein the micronized NMDA receptor antagonist, or pharmaceutically acceptable salt thereof is not provided as polymer-containing particles, and is suspended in the auris acceptable gel.   
     
     
         22 . The intratympanic composition of  claim 21 , wherein the auris acceptable gel is an auris acceptable hydrogel. 
     
     
         23 . The intratympanic composition of  claim 21 , wherein the auris acceptable gel has a gelation viscosity between about 15,000 cP and about 1,000,000 cP. 
     
     
         24 . The intratympanic composition of  claim 21 , wherein the auris acceptable gel is capable of being injected by a narrow gauge needle or cannula through the tympanic membrane. 
     
     
         25 . The intratympanic composition of  claim 21 , wherein the intratympanic composition has an osmolarity of from about 100 mOsm/L to about 1000 mOsm/L. 
     
     
         26 . The intratympanic composition of  claim 21 , wherein the intratympanic composition has a pH between 7.0 and 8.0. 
     
     
         27 . The intratympanic composition of  claim 21 , wherein the auris acceptable gel comprises sodium hyaluronate. 
     
     
         28 . The intratympanic composition of  claim 21 , wherein the otic disease or condition is tinnitus. 
     
     
         29 . The intratympanic composition of  claim 21 , wherein sustained release of ketamine into the ear occurs for a period of at least 3 days after a single administration. 
     
     
         30 . The intratympanic composition of  claim 21 , wherein sustained release of ketamine into the ear occurs for a period of at least 5 days after a single administration. 
     
     
         31 . An intratympanic composition for use in the treatment of an otic disease or condition, the intratympanic composition comprising
 a micronized MAPK/JNK signaling cascade modulator, or pharmaceutically acceptable thereof, wherein the MAPK/JNK signaling cascade modulator is D-JNKI-1; and   an auris acceptable gel,   wherein the micronized MAPK/JNK signaling cascade modulator, or pharmaceutically acceptable prodrug or salt thereof is not provided as polymer-containing particles, and is suspended in the auris acceptable gel.   
     
     
         32 . The intratympanic composition of  claim 31 , wherein the auris acceptable gel is an auris acceptable hydrogel. 
     
     
         33 . The intratympanic composition of  claim 31 , wherein the auris acceptable gel has a gelation viscosity between about 15,000 cP and about 1,000,000 cP. 
     
     
         34 . The intratympanic composition of  claim 31 , wherein the auris acceptable gel is capable of being injected by a narrow gauge needle or cannula through the tympanic membrane. 
     
     
         35 . The intratympanic composition of  claim 31 , wherein the intratympanic composition has an osmolarity of from about 100 mOsm/L to about 1000 mOsm/L. 
     
     
         36 . The intratympanic composition of  claim 31 , wherein the intratympanic composition has a pH between 7.0 and 8.0. 
     
     
         37 . The intratympanic composition of  claim 31 , wherein the auris acceptable gel comprises sodium hyaluronate. 
     
     
         38 . The intratympanic composition of  claim 31 , wherein the otic disease or condition is sensorineural hearing loss. 
     
     
         39 . The intratympanic composition of  claim 31 , wherein sustained release of D-JNKI-1 into the ear occurs for a period of at least 3 days after a single administration. 
     
     
         40 . The intratympanic composition of  claim 31 , wherein sustained release of D-JNKI-1 into the ear occurs for a period of at least 5 days after a single administration.