Method for treating gastrointestinal disorder

Abstract

The present invention relates to a method for the long term treatment of gastrointestinal disorders in a human subject, which comprises administering an effective amount of a halogenated prostaglandin compound and/or its tautomer to the subject. The method induces substantially no electrolyte shifting during the term of the treatment. The compound used in the present invention can improve quality of life in the human subjects with gastrointestinal disorders, are similarly effective in treating male and female subjects, and also effective in a human subject aged even 65 years and older.

What is claimed is: 
     
         1 . A method for the long term treatment of gastrointestinal disorders in a human subject, which comprises administering to the subject in need thereof an effective amount of a prostaglandin compound represented by Formula (I) and/or its tautomer: 
       
         
           
           
               
               
           
         
         wherein W 1  and W 2  are 
       
       
         
           
           
               
               
           
         
         R 3  and R 4  are hydrogen; or one of them is OH and the other is hydrogen; 
         X 1  and X 2  are hydrogen, lower alkyl or halogen, provided that at least one of them is halogen; 
         R 2  is hydrogen or alkyl; 
         Y is a saturated or unsaturated hydrocarbon chain, which is unsubstituted or substituted by oxo, halogen, alkyl, hydroxy or aryl; 
         A is —CH 2 OH, —COCH 2 CH, —COOH or its functional derivative; 
         R 1  is a saturated or unsaturated, straight chain-, branched chain- or ring-forming lower hydrocarbon, which is unsubstituted or substituted by halogen, oxo, hydroxy, lower alkyl, lower alkoxy, lower alkanoyloxy, lower cycloalkyl, lower cycloalkyloxy, aryl, or aryloxy; lower cycloalkyl; lower cycloalkyloxy; aryl; or aryloxy; 
         the bond between C-13 and C-14 positions is double or single bond, and 
         the steric configuration at C-15 position is R, S or a mixture thereof. 
       
     
     
         2 . The method of  claim 1 , wherein said prostaglandin compound is a monocyclic tautomer of formula (I). 
     
     
         3 . The method of  claim 1 , wherein the amount of said prostaglandin compound to be administered is in the range of about 6-96 μg per day. 
     
     
         4 . The method of  claim 1 , wherein the amount of said prostaglandin compound to be administered is in the range of about 6-72 μg per day. 
     
     
         5 . The method of  claim 1 , wherein the amount of said prostaglandin compound to be administered is in the range of about 6-60 μg per day. 
     
     
         6 . The method of  claim 1 , wherein the amount of said prostaglandin compound to be administered is in the range of about 8-48 μg per day. 
     
     
         7 . The method of  claim 1 , wherein the prostaglandin compound is administered orally. 
     
     
         8 . The method of  claim 7 , wherein said prostaglandin compound is administered with an oil solvent as an excipient. 
     
     
         9 . The method of  claim 8 , wherein said oil solvent is a medium chain fatty acid. 
     
     
         10 . The method of  claim 1 , wherein A is —COOH; Y is (CH 2 ) 6 ; W 1  is ═O; W 2  is 
       
         
           
           
               
               
           
         
       
       wherein R 3  and R 4  are both hydrogen atoms; R 2  is hydrogen atom, X 1  and X 2  are fluorine atoms; and R 1  is (CH 2 ) 3 CH 3 . 
     
     
         11 . The method of  claim 1 , wherein said gastrointestinal disorder is selected from the group consisting of constipation, irritable bowel syndrome and functional dyspepsia. 
     
     
         12 . The method of  claim 1 , wherein said prostaglandin compound is administered for at least two weeks. 
     
     
         13 . The method of  claim 1 , wherein said prostaglandin compound is administered for at least three weeks. 
     
     
         14 . The method of  claim 1 , wherein said prostaglandin compound is administered for at least four weeks. 
     
     
         15 . The method of  claim 1 , wherein said prostaglandin is administered for at least 2 months. 
     
     
         16 . The method of  claim 1 , wherein said prostaglandin is administered for at least 6 months. 
     
     
         17 . The method of  claim 1 , wherein said prostaglandin is administered for at least 1 year. 
     
     
         18 . The method of  claim 1 , wherein said prostaglandin is administered chronically. 
     
     
         19 . A method for treating gastrointestinal disorders in a human subject aged 65 years and older, which comprises administering to the subject aged 65 years and older in need thereof an effective amount of a prostaglandin compound represented by Formula (I) and/or its tautomer: 
       
         
           
           
               
               
           
         
         wherein W 1  and W 2  are 
       
       
         
           
           
               
               
           
         
         R 3  and R 4  are hydrogen; or one of them is OH and the other is hydrogen; 
         X 1  and X 2  are hydrogen, lower alkyl or halogen, provided that at least one of them is halogen; 
         R 2  is hydrogen or alkyl; 
         Y is a saturated or unsaturated C 2-10  hydrocarbon chain, which is unsubstituted or substituted by oxo, halogen, alkyl, hydroxy or aryl; 
         A is —CH 2 OH, —COCH 2 OH, —COOH or its functional derivative; 
         R 1  is a saturated or unsaturated, straight chain-, branched chain- or ring-forming lower hydrocarbon, which is unsubstituted or substituted by halogen, oxo, hydroxy, lower alkyl, lower alkoxy, lower alkanoyloxy, lower cycloalkyl, lower cycloalkyloxy, aryl, or aryloxy; lower cycloalkyl; lower cycloalkyloxy; aryl; or aryloxy; 
         the bond between C-13 and C-14 positions is double or single bond, and 
         the steric configuration at C-15 position is R, S or a mixture thereof. 
       
     
     
         20 . A method for improving quality of life in a human subject with gastrointestinal disorders, which comprises administering to the subject an effective amount of a prostaglandin compound represented by Formula (I) and/or its tautomer: 
       
         
           
           
               
               
           
         
         wherein W 1  and W 2  are 
       
       
         
           
           
               
               
           
         
         R 3  and R 4  are hydrogen; or one of them is OH and the other is hydrogen; 
         X 1  and X 2  are hydrogen, lower alkyl or halogen, provided that at least one of them is halogen; 
         R 2  is hydrogen or alkyl; 
         Y is a saturated or unsaturated C 2-10  hydrocarbon chain, which is unsubstituted or substituted by oxo, halogen, alkyl, hydroxy or aryl; 
         A is —CH 2 OH, —COCH 2 OH, —COOH or its functional derivative; 
         R 1  is a saturated or unsaturated, straight chain-, branched chain- or ring-forming lower hydrocarbon, which is unsubstituted or substituted by halogen, oxo, hydroxy, lower alkyl, lower alkoxy, lower alkanoyloxy, lower cycloalkyl, lower cycloalkyloxy, aryl, or aryloxy; lower cycloalkyl; lower cycloalkyloxy; aryl; or aryloxy; 
         the bond between C-13 and C-14 positions is double or single bond, and 
         the steric configuration at C-15 position is R, S or a mixture thereof.