Doxepin trans isomers and isomeric mixtures and methods of using the same to treat sleep disorders

Abstract

The invention relates to use of the trans-(E) isomer or isomeric mixtures containing specified ratios of the trans-(E) and cis-(Z) isomers of doxepin, metabolites of doxepin, pharmaceutically-acceptable salts of doxepin and prodrugs of the same; compositions containing the same, for the treatment of sleep disorders

1 . A method for the treatment of a patient suffering from insomnia comprising administering to said patient doxepin, a pharmaceutically-acceptable salt or a prodrug thereof in a daily dosage ranging from about 0.0001 to about 499 milligrams, wherein the doxepin, the salt or the prodrug is a geometric isomer mixture containing about 88.3% to about 100.0% of the trans-(E) isomer or is 100% trans-(E) isomer. 
   
   
       2 . The method of  claim 1 , wherein said geometric isomer mixture contains more than 90% of the trans-(E) isomer. 
   
   
       3 . The method of  claim 1 , wherein said geometric isomer mixture contains more than 95% of the trans-(E) isomer. 
   
   
       4 . The method of  claim 1 , wherein said geometric isomer mixture contains more than 98% of the trans-(E) isomer. 
   
   
       5 . The method of  claim 1 , wherein said geometric isomer mixture contains more than 99% of the trans-(E) isomer. 
   
   
       6 . The method of  claim 1 , wherein said geometric isomer mixture contains at least 99.5% or 99.9% of the trans-(E) isomer. 
   
   
       7 . The method of  claim 1 , wherein said geometric isomer mixture contains 100.0% of the trans-(E) isomer. 
   
   
       8 . The method of  claim 1 , wherein said geometric isomer mixture contains about 89% to about 99.9% of the trans-(E) isomer. 
   
   
       9 - 20 . (canceled) 
   
   
       21 . The method of  claim 1 , wherein the daily dosage is about 0.01 to about 20 milligrams. 
   
   
       22 - 31 . (canceled) 
   
   
       32 . A composition comprising a pharmaceutically-acceptable carrier and doxepin, a pharmaceutically-acceptable salt of doxepin, or a prodrug of doxepin in a unit dosage form of about 0.0001 milligrams to about 499 milligrams, wherein the doxepin, the salt or the prodrug is a geometric isomer mixture containing about 88.3% to about 100.0% of the trans-(E) isomer or is 100% trans-(E) isomer. 
   
   
       33 . The composition of  claim 32 , wherein said geometric isomer mixture contains more than 90% of the trans-(E) isomer. 
   
   
       34 - 38 . (canceled) 
   
   
       39 . The composition of  claim 32 , wherein said geometric isomer mixture contains about 89% to about 99.9% of the trans-(E) isomer. 
   
   
       40 - 50 . (canceled) 
   
   
       51 . The composition of  claim 32 , wherein the amount is about 0.1 to about 20 milligrams. 
   
   
       52 - 58 . (canceled) 
   
   
       59 . A method for treating insomnia comprising administering to a patient a metabolite of doxepin, a pharmaceutically-acceptable salt thereof, or a prodrug thereof in a dosage ranging from about 0.0001 to about 499 milligrams, wherein the metabolite of doxepin, the salt or the prodrug is a geometric isomer mixture containing about 88.3% to about 100.0% of the trans-(E) isomer or is 100% trans-(E) isomer. 
   
   
       60 - 86 . (canceled) 
   
   
       87 . A composition comprising a pharmaceutically-acceptable carrier and a metabolite of doxepin, a pharmaceutically-acceptable salt of the metabolite, or a prodrug of the metabolite in unit dosage form of about 0.0001 milligrams to about 499 milligrams, wherein doxepin, the salt or the prodrug is a geometric isomer mixture containing about 88.3% to about 100.0% of the trans-(E) isomer of the metabolite or is 100% trans-(E) isomer. 
   
   
       88 - 117 . (canceled)