Pharmaceutical Compositions for the Treatment of Inner Ear Disorders

Abstract

The present invention provides compositions containing (i) a pharmaceutically active agent selected from a group consisting of an arylcycloalkyamine or a derivative, analogue or pharmaceutically active salt thereof, and (ii) a biocompatible polymer or a combination of biocompatible polymers. These compositions or medicaments containing these compositions may be used for the prevention and/or treatment of inner ear diseases, e.g. tinnitus.

1 . A composition containing (i) a pharmaceutically active agent selected from a group consisting of an arylcycloalkyamine or a derivative, analogue or pharmaceutically active salt thereof, and (ii) a biocompatible polymer or a combination of biocompatible polymers. 
   
   
       2 . Composition according to  claim 1 , wherein the composition is solid, semi-solid, gel-like, or liquid. 
   
   
       3 . Composition according to  claim 1  or  2 , wherein the composition is a solution, suspension, an emulsion or a thermosetting gel. 
   
   
       4 . Composition according to any of preceding  claims 1  to  3 , wherein the biocompatible polymer is selected from the group consisting of naturally occurring polysaccharides or synthetic polymers or a mixture thereof. 
   
   
       5 . Composition according to  claim 4 , wherein the biocompatible polymer is selected from block (co)polymers. 
   
   
       6 . Composition according to  claim 4  or  5 , wherein the biocompatible polymer is selected from hyaluronic acid, lecithin gels, (poly)alanine derivatives, pluronics, poly(ethylene)glycol, poloxamer, chitosan, xyloglucane, collagen, fibrin or a mixture thereof. 
   
   
       7 . Composition according to any of preceding  claims 4  to  6 , wherein the biocompatible polymer is biodegradable. 
   
   
       8 . Composition according to any of preceding  claims 1  to  7 , wherein the arylcycloalkylamine is an NMDA antagonist. 
   
   
       9 . Composition according to  claim 7  or  8 , wherein the arylcycloalkylamine has the general formula I: 
     
       
         
         
             
             
         
       
     
     wherein R1, R2, R3, R4, R5, R6 and R7 are H, Cl, F, I, CH 3 , CH 2 CH 3 , NH 2 , OH, CONH 2 , COCl or COOH. 
   
   
       10 . Composition according to any of preceding  claims 7  to  9 , wherein the pharmaceutically active agent is 2-(2-chlorophenyl)-2-(methylamino)-cyclohexanone (ketamine), preferably (S)-ketamine. 
   
   
       11 . Composition according to any of preceding  claims 1  to  10  containing further components selected from the group consisting of pharmaceutically acceptable vehicles, buffers, excipients, additives and substances increasing the permeability of the middle-inner ear interface tissue structure. 
   
   
       12 . Composition according to  claim 11 , wherein the substance increasing the permeability is histamine. 
   
   
       13 . A medicament containing a composition according to  claims 1  to  12 . 
   
   
       14 . Medicament according to  claim 13  formed as a release-of-drug-formulation. 
   
   
       15 . Medicament according to  claim 13  or  14 , wherein the medicament as release-of-drug-formulation releases the pharmaceutically active agent over several hours up to several weeks. 
   
   
       16 . Medicament according to any of preceding  claims 14  to  15  being injectable and modifying its viscosity upon insertion into the middle ear. 
   
   
       17 . Medicament according to  claims 13  to  16  altering its release profile by exposition to chemical agents. 
   
   
       18 . Medicament according to  claims 13  to  17  for targeted release at the selected middle-inner ear interface tissue structure by bio-adhesion or mechanical properties. 
   
   
       19 . Medicament according to  claims 13  to  18  which is provided in form of an implant. 
   
   
       20 . Use of a composition according to  claims 1  to  12  for the preparation of a medicament or use of a medicament according to  claims 13  to  19  for treating inner ear diseases. 
   
   
       21 . Use of a composition according to  claim 20  for the treatment of tinnitus, hearing loss, inner ear inflammations or infections, auto-immune disorders, vertigo or Meniere's Disease. 
   
   
       22 . Use according to  claim 20  or  21  for the preparation of a medicament for the treatment of excitotoxicity-induced ear cell degeneration or age-induced ear cell degeneration. 
   
   
       23 . Method of treating the inner ear of a mammal suffering from an inner disease by administering a composition according to  claims 1  to  12  or a medicament according to  claims 13  to  19  to a mammal suffering from an inner ear disease. 
   
   
       24 . Method according to  claim 23 , wherein the composition is administered by inserting it into the middle ear. 
   
   
       25 . Method according to  claim 24 , wherein the composition is administered by infusion, injection or by deposition by means of a surgical instrument.