Method for treating irritable bowel syndrome by administration of chloride channel opener

Abstract

A chloride channel opener, especially a prostaglandin compound, is used for the treatment of functional gastrointestinal disorders. The prostaglandin compound can be, for example, a 13,14-dihydro-15-keto-16,16-difluoro-prostaglandin E 1 compound or 13,14-dihydro-15-keto-16,16-difluoro-18-methyl-prostaglandin E 1 compound. The functional gastrointestinal disorders can be, for example, irritable bowel syndrome and/or functional dyspepsia. The treatment can include, for example, systemic administration 1-4 times per day or continuous administration of the compound in an amount of 0.01-100 μg per day.

What is claimed is: 
     
         1 . A method for treating irritable bowel syndrome in a mammalian subject, which comprises administration of an effective amount of a chloride channel opener to the subject. 
     
     
         2 . The method as described in  claim 1 , wherein said chloride channel opener is a ClC channel opener. 
     
     
         3 . The method as described in  claim 2 , wherein said ClC channel opener is a ClC-2 channel opener. 
     
     
         4 . The method as described in  claim 1 , wherein said chloride channel opener is a prostaglandin compound. 
     
     
         5 . The method as described in  claim 4 , wherein said prostaglandin compound is the compound as shown by the following formula (I): 
       
         
           
           
               
               
           
         
         wherein L, M and N are hydrogen atom, hydroxy, halogen atom, lower alkyl, hydroxy (lower) alkyl , lower alkanoyloxy or oxo, wherein at least one of L and M is a group other than hydrogen, and the five-membered ring may have at least one double bond; 
         A is —CH 3 , or —CH 2 OH, —COCH 2 OH, —COOH or a salt, ether, Ester or amide thereof; 
         B is single bond, —CH 2 —CH 2 —, —CH═CH—, —C≡C—, d—CH 2 —CH 2 —CH 2 —, —CH═CH—CH 2 —, —CH 2 —CH═CH—, —C≡C—CH 2 — or —CH 2 —C≡C—; 
         Z is 
       
       
         
           
           
               
               
           
         
         or single bond 
         wherein R 4  and R 5  are hydrogen, hydroxy, halogen, lower alkyl, lower alkoxy or hydroxy(lower)alkyl, wherein R 4  and R 5  are not hydroxy and lower alkoxy at the same time; 
         R 1  is a saturated or unsaturated bivalent lower or medium aliphatic hydrocarbon residue, which is unsubstituted or substituted with halogen, alkyl, hydroxy, oxo, aryl or heterocyclic group selected from the group consisting of furyl, thienyl, pyrrolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, imidazolyl, pyrazolyl, furazanyl, pyranyl, pyridyl, pyridazinyl, pyrimidyl, pyrazinyl, 2-pyrrolinyl, pyrrolidinyl, 2-imidazolinyl, imidazolidinyl, 2-pyrazolinyl, pyrazolidinyl, piperidino, piperazinyl, morpholino, indolyl, benzothienyl, quinolyl, isoquinolyl, purinyl, quinazolinyl, carbazolyl, acridinyl, phenanthridinyl, benzimidazolyl, benzimidazolinyl, benzothiazolyl and phenothiazinyl, and at least one of carbon atom in the aliphatic hydrocarbon is optionally substituted by oxygen, nitrogen or sulfur; and 
         Ra is a saturated or unsaturated straight or branched chain hydrocarbon group having 1 to 14 carbon atoms, which is unsubstituted or substituted with halogen, oxo, hydroxy, lower alkyl, lower alkoxy, lower alkanoyloxy, cyclo(lower)alkyl, cyclo(lower)alkyloxy, aryl, aryloxy, heterocyclic group selected from the group consisting of furyl, thienyl, pyrrolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, imidazolyl, pyrazolyl, furazanyl, pyranyl, pyridyl, pyridazinyl, pyrimidyl, pyrazinyl, 2-pyrrolinyl, pyrrolidinyl, 2-imidazolinyl, imidazolidinyl, 2-pyrazolinyl, pyrazolidinyl, piperidino, piperazinyl, morpholino, indolyl, benzothienyl, quinolyl, isoquinolyl, purinyl, quinazolinyl, carbazolyl, acridinyl, phenanthridinyl, benzimidazolyl, benzimidazolinyl, benzothiazolyl and phenothiazinyl, or heterocyclic-oxy group; lower alkoxy; lower alkanoyloxy; cyclo(lower)alkyl; cyclo(lower)alkyloxy; aryl; aryloxy; heterocyclic group selected from the group consisting of furyl, thienyl, pyrrolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, imidazolyl, pyrazolyl, furazanyl, pyranyl, pyridyl, pyridazinyl, pyrimidyl, pyrazinyl, 2-pyrrolinyl, pyrrolidinyl, 2-imidazolinyl, imidazolidinyl, 2-pyrazolinyl, pyrazolidinyl, piperidino, piperazinyl, morpholino, indolyl, benzothienyl, quinolyl, isoquinolyl, purinyl, quinazolinyl, carbazolyl, acridinyl, phenanthridinyl, benzimidazolyl, benzimidazolinyl, benzothiazolyl and phenothiazinyl; heterocyclic-oxy. 
       
     
     
         6 . The method as described in  claim 4 , wherein said prostaglandin compound is 16-mono or dihalogen-prostaglandin compound. 
     
     
         7 . The method as described in  claim 4 , wherein said prostaglandin compound is 13,14-dihydro-16-mono or dihalogen-prostaglandin compound. 
     
     
         8 . The method as described in  claim 4 , wherein said prostaglandin compound is 13,14-dihydro-15-keto-16-mono or dihalogen-prostaglandin compound. 
     
     
         9 . The method as described in  claim 4 , wherein said prostaglandin compound is 13,14-dihydro-16-mono or difluoro-prostaglandin compound. 
     
     
         10 . The method as described in  claim 4 , wherein said prostaglandin compound is 13,14-dihydro-15-keto-16-mono or difluoro-prostaglandin compound. 
     
     
         11 . The method as described in  claim 4 , wherein said prostaglandin compound is 13,14-dihydro-16-mono or dihalogen-prostaglandin E compound. 
     
     
         12 . The method as described in  claim 4 , wherein said prostaglandin compound is 13,14-dihydro-15-keto-16-mono or dihalogen-prostaglandin E compound. 
     
     
         13 . The method as described in  claim 4 , wherein said prostaglandin compound is 13,14-dihydro-16,16-difluoro-prostaglandin E 1  compound. 
     
     
         14 . The method as described in  claim 4 , wherein said prostaglandin compound is 13,14-dihydro-15-keto-16,16-difluoro-prostaglandin E 1  compound or 13,14-dihydro-15-keto-16,16-difluoro-18-methyl-prostaglandin E 1  compound. 
     
     
         15 . The method as described in  claim 4 , which comprises systemic administration 1-4 times per day or continuous administration at the amount of 0.01-100 μg/kg per day. 
     
     
         16 . The method as described in  claim 4 , wherein the administration is at the amount of 0.1-10 μg/kg per day.