Anti-constipation composition

Abstract

An object of the present invention is to provide an anti-constipation composition containing a halogenated-bi-cyclic compound as an active ingredient in a ratio of bi-cyclic/mono-cyclic structure of at least 1:1. The halogenated-bi-cyclic compound is represented by Formula (I): where X 1 and X 2 are preferably both fluorine atoms. The composition can be used to treat constipation without substantive side-effects, such as stomachache.

What is claimed is: 
     
         1 . A pharmaceutical composition comprising a bi-cyclic compound represented by formula (I) in an amount therapeutically effective for relieving or preventing constipation in a constipated human patient, or for preparation of a bowel prior to preventative, diagnostic or surgical procedures: 
       
         
           
           
               
               
           
         
         where V 1  and V 2  are carbon or oxygen atoms; 
         W 1  and W 2  are 
       
       
         
           
           
               
               
           
         
         R 3  and R 4  are hydrogen atoms or one of them is OH; 
         X 1  and X 2  are hydrogen, lower alkyl or halogen atom, and at least one of these is a halogen atom; 
         Z is a carbon, sulfur or nitrogen atom; 
         R 2  is a hydrogen atom or alkyl; 
         Y is a saturated or unsaturated C 2-10  hydrocarbon chain which is unsubstituted or substituted by oxo, halogen, an alkyl group, hydroxyl or aryl; 
         A is —CH 2 OH, —COCH 2 OH, —COOH or its functional derivative; and 
         R 1  is a saturated or unsaturated, lower hydrocarbon forming a straight-chain, a branched-chain or a ring, which is unsubstituted or substituted by halogen, oxo, hydroxy, lower alkoxy, lower alkanoyloxy, lower cycloalkyl, lower cycloalkyloxy, aryl, or aryloxy; lower cycloalkyl; lower cycloalkyloxy; aryl or aryloxy, 
         a bond between C-13 and C-14 position can be a double or single bond, and 
         C-15 can have a steric configuration of R, S, or a mixture thereof. 
       
     
     
         2 . The pharmaceutical composition according to  claim 1 , further comprising a compound which is a mono-cyclic tautomer of formula (I),
 wherein in the composition a ratio of bi-cyclic to mono-cyclic structure is at least 1:1.   
     
     
         3 . The pharmaceutical composition according to  claim 1 , further comprising a compound which is a mono-cyclic tautomer of formula (I),
 wherein in the composition a ratio of bi-cyclic/mono-cyclic structure is at least 20:1.   
     
     
         4 . A pharmaceutical composition comprising a bi-cyclic compound represented by the following formula (I) in an amount therapeutically effective for relieving or preventing constipation in a constipated human patient, or for preparation of a bowel prior to preventative, diagnostic or surgical procedures; 
       
         
           
           
               
               
           
         
         where V 1  and V 2  are carbon or oxygen atoms; 
         W 1  and W 2  are 
       
       
         
           
           
               
               
           
         
         R 3  and R 4  are hydrogen atoms or one of them is OH; 
         X 1  and X 2  are hydrogen, lower alkyl or halogen atom, and at least one of these is a halogen atom; 
         Z is a carbon, sulfur or nitrogen atom; 
         R 2  is a hydrogen atom or alkyl; 
         Y is a saturated or unsaturated C 2-10  hydrocarbon chain which is unsubstituted or substituted by oxo, halogen, an alkyl group, hydroxyl or aryl; 
         A is —CH 2 OH, —COCH 2 OH, —COOH or its functional derivative; and 
         R 1  is a saturated or unsaturated, lower hydrocarbon forming a straight-chain, a branched-chain or a ring, which is unsubstituted or substituted by halogen, oxo, hydroxy, lower alkoxy, lower alkanoyloxy, lower cycloalkyl, lower cycloalkyloxy, aryl, or aryloxy; lower cycloalkyl; lower cycloalkyloxy; aryl or aryloxy, 
         a bond between C-13 and C-14 position can be a double or single bond, 
         C-15 can have a steric configuration of R, S, or a mixture thereof, 
         and medium chain fatty acid triglyceride. 
       
     
     
         5 . The pharmaceutical composition according to  claim 4 , further comprising a compound which is a mono-cyclic tautomer of formula (I),
 wherein in the composition a ratio of bi-cyclic/monocyclic structure is at least 1:1.   
     
     
         6 . The pharmaceutical composition according to  claim 5 , wherein the ratio of bi-cyclic/mono-cyclic structure is at least 20:1. 
     
     
         7 . The pharmaceutical composition of according to  claim 1 , wherein Z is a sulfur atom or a nitrogen atom. 
     
     
         8 . The pharmaceutical composition according to  claim 4 , wherein Z is a sulfur atom or a nitrogen atom. 
     
     
         9 . The pharmaceutical composition according to  claim 4 , wherein the medium chain fatty acid triglyceride is present in an amount of 1-1,000,000 parts by weight based on one part by weight of the bi-cyclic structure. 
     
     
         10 . The pharmaceutical composition according to  claim 9 , wherein the medium chain fatty acid triglyceride is present in an amount of 5-500,000 parts by weight based on one part by weight of the bi-cyclic structure. 
     
     
         11 . The pharmaceutical composition according to  claim 9 , wherein the medium chain fatty acid triglyceride is present in an amount of 10-200,000 parts by weight based on one part by weight of the bi-cyclic structure. 
     
     
         12 . The pharmaceutical composition according to  claim 4 , wherein the medium chain fatty acid triglyceride is a triglyceride of a fatty acid having 6-14 carbon atoms. 
     
     
         13 . The pharmaceutical composition according to  claim 4 , wherein the medium chain fatty acid triglyceride is caprylic acid triglyceride and/or capric triglyceride. 
     
     
         14 . A method for relieving or preventing constipation in a human constipated patient or preparing a bowel prior to preventative, diagnostic or surgical procedures which comprises administering to the patient a therapeutically effective amount of the pharmaceutical composition of  claim 1 . 
     
     
         15 . A method for relieving or preventing constipation in a human constipated patient or preparing a bowel prior to preventative, diagnostic or surgical procedures which comprises administering to the patient a therapeutically effective amount of the pharmaceutical composition of  claim 2 . 
     
     
         16 . A method for relieving or preventing constipation in a human constipated patient or preparing a bowel prior to preventative, diagnostic or surgical procedures which comprises administering to the patient a therapeutically effective amount of the pharmaceutical composition of  claim 3 . 
     
     
         17 . A method for relieving or preventing constipation in a human constipated patient or preparing a bowel prior to preventative, diagnostic or surgical procedures which comprises administering to the patient a therapeutically effective amount of the pharmaceutical composition of  claim 4 . 
     
     
         18 . A method for relieving or preventing constipation in a human constipated patient or preparing a bowel prior to preventative, diagnostic or surgical procedures which comprises administering to the patient a therapeutically effective amount of the pharmaceutical composition of  claim 5 . 
     
     
         19 . A method for relieving or preventing constipation in a human constipated patient or preparing a bowel prior to preventative, diagnostic or surgical procedures which comprises administering to the patient a therapeutically effective amount of the pharmaceutical composition of  claim 6 . 
     
     
         20 . A method for relieving or preventing constipation in a human constipated patient or preparing a bowel prior to preventative, diagnostic or surgical procedures which comprises administering to the patient a therapeutically effective amount of the pharmaceutical composition of  claim 7 .