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, oxygen, 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 . The pharmaceutical composition according to  claim 1 , wherein A is —COOH, W 1  is a ketone, Z is an oxygen atom, R 2  is a hydrogen atom, and X 1  and X 2  are fluorine atoms.  
     
     
         5 . 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, oxygen, 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.  
 
     
     
         6 . The pharmaceutical composition according to  claim 5 , further comprising a compound which is a mono-cyclic tautomer of formula (1), 
 wherein in the composition a ratio of bi-cyclic/monocyclic structure is at least 1:1.    
     
     
         7 . The pharmaceutical composition according to  claim 6 , wherein the ratio of bi-cyclic/mono-cyclic structure is at least 20:1.  
     
     
         8 . The pharmaceutical composition according to  claim 5 , wherein A is —COOH, W 1  is a ketone, Z is an oxygen atom, and X 1  and X 2  are fluorine atoms.  
     
     
         9 . The pharmaceutical composition of according to  claim 1 , wherein Z is a sulfur atom or a nitrogen atom.  
     
     
         10 . The pharmaceutical composition according to  claim 5 , wherein Z is a sulfur atom or a nitrogen atom.  
     
     
         11 . The pharmaceutical composition according to  claim 5 , 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  
     
     
         12 . The pharmaceutical composition according to  claim 11 , 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.  
     
     
         13 . The pharmaceutical composition according to  claim 11 , 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.  
     
     
         14 . The pharmaceutical composition according to  claim 5 , wherein the medium chain fatty acid triglyceride is a triglyceride of a fatty acid having 6-14 carbon atoms.  
     
     
         15 . The pharmaceutical composition according to  claim 5 , wherein the medium chain fatty acid triglyceride is caprylic acid triglyceride and/or capric triglyceride.  
     
     
         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 1 .  
     
     
         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 2 .  
     
     
         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 3 .  
     
     
         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 4 .  
     
     
         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 5 .  
     
     
         21 . 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 .  
     
     
         22 . 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 .  
     
     
         23 . 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 8 .  
     
     
         24 . 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 9 .  
     
     
         25 . 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 10 .  
     
     
         26 . 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 11   
     
     
         27 . 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 12 .  
     
     
         28 . 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 13 .  
     
     
         29 . 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 14 .  
     
     
         30 . 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 15 .  
     
     
         31 . A pharmaceutical composition according to  claim 1 , wherein A is COOH; Y is (CH 2 ) 6 ; W 1  is ═O; R 3  and R 4  are hydrogen atoms; V 1  and V 2  are carbon atoms; Z is a oxygen atom, X 1  and X 2  are fluorine atoms; and R 1  is (CH 2 ) 3 CH 3 .  
     
     
         32 . A pharmaceutical composition according to  claim 5 , wherein A is COOH; Y is (CH 2 ) 6 ; W 1  is ═O; R 3  and R 4  are hydrogen atoms; V 1  and V 2  are carbon atoms; Z is a oxygen atom, X 1  and X 2  are fluorine atoms; and R 1  is (CH 2 ) 3 CH 3 .  
     
     
         33 . 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 31 .  
     
     
         34 . 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 32.