Diagnostic agents for pancreatic exocrine function

Abstract

The present invention provides a 13 C-labeled oligosaccharide or polysaccharide or a salt thereof excluding U- 13 C-maltose, 13 C-starch, 1 - 13 C-maltotetraose and 1 - 13 C-amylose; a derivative of the 13 C-labeled oligosaccharide or polysaccharide or salt thereof; a 13 C-labeled inclusion complex or a salt thereof, which comprises a cyclodextrin or a modified derivative thereof as a host molecule; a 13 C- or 14 C-labeled fluorescein ester compound or a salt thereof; and a diagnostic agents for pancreatic exocrine function comprising these compounds 13 C- or 14 C-labeled.

1 . A  13 C-labeled oligosaccharide or polysaccharide or a salt thereof excluding U- 13 C-maltose,  13 C-starch, 1- 13 C-maltotetraose and 1- 13 C-amylose.  
     
     
         2 . The  13 C-labeled oligosaccharide or polysaccharide or salt thereof according to  claim 1 , which is hydrolyzed with α-amylase.  
     
     
         3 . The  13 C-labeled oligosaccharide or polysaccharide or salt thereof according to  claim 2 , which is not hydrolyzed with α-glucosidase.  
     
     
         4 . The  13 C-labeled oligosaccharide or polysaccharide or salt thereof according to any one of  claims 1  to  3 , wherein at least one sugar molecule constituting the oligosaccharide or polysaccharide is  13 C-labeled.  
     
     
         5 . The  13 C-labeled oligosaccharide or polysaccharide or salt thereof according to any one of  claims 1  to  3 , wherein at least one sugar molecule constituting the oligosaccharide or polysaccharide is modified with at least one  13 C-labeled modifying group.  
     
     
         6 . The  13 C-labeled oligosaccharide or polysaccharide or salt thereof according to any one of  claims 1  to  5 , which is a linear or branched oligosaccharide or polysaccharide.  
     
     
         7 . The  13 C-labeled oligosaccharide or polysaccharide or salt thereof according to any one of  claims 1  to  5 , which is a cyclic oligosaccharide or polysaccharide.  
     
     
         8 . The  13 C-labeled oligosaccharide or polysaccharide or salt thereof according to  claim 6 , which is modified at the non-reducing terminal.  
     
     
         9 . The  13 C-labeled oligosaccharide or polysaccharide or salt thereof according to  claim 1 , which is a  13 C-cyclodextrin or β-galactosyl- 13 C-maltooligosaccharide.  
     
     
         10 . A derivative of the  13 C-labeled oligosaccharide or polysaccharide or salt thereof according to any one of  claims 1  to  9 .  
     
     
         11 . A  13 C-labeled inclusion complex or a salt thereof, which comprises a cyclodextrin or a modified derivative thereof as a host molecule.  
     
     
         12 . The inclusion complex or salt thereof according to  claim 11 , wherein the host molecule is  13 C-labeled.  
     
     
         13 . The inclusion complex or salt thereof according to  claim 11 , wherein the guest molecule is  13 C-labeled.  
     
     
         14 . The inclusion complex or salt thereof according to any one of  claims 11  to  13 , wherein the guest molecule is selected from the group consisting of oligosaccharides, amino acids, peptides, organic acids, fatty acids, fatty acid glycerides, vitamins, catechins, carotinoids, flavonoids and cholesterol.  
     
     
         15 . The inclusion complex or salt thereof according to  claim 14 , wherein the guest molecule is selected from the group consisting of  13 C-phenylalanine, benzoylphenylalanyl- 13 C-leucine and benzoylphenylalanyl- 13 C-leucine methyl ester.  
     
     
         16 . A diagnostic agent for pancreatic exocrine function comprising a  13 C or  14 C-labeled oligosaccharide or polysaccharide or a salt thereof or a derivative thereof other than  13 C-starch.  
     
     
         17 . The diagnostic agent for pancreatic exocrine function according to  claim 16 , wherein the  13 C- or  14 C-labeled oligosaccharide or polysaccharide or salt thereof or derivative thereof is hydrolyzed with β-amylase.  
     
     
         18 . The diagnostic agent for pancreatic exocrine function according to  claim 17 , wherein the  13 C- or  14 C-labeled oligosaccharide or polysaccharide or salt thereof or derivative thereof is not hydrolyzed with α-glucosidase.  
     
     
         19 . The diagnostic agent for pancreatic exocrine function according to any one of  claims 16  to  18 , wherein the  13 C or  14 C-labeled oligosaccharide or polysaccharide is a linear or branched oligosaccharide or polysaccharide.  
     
     
         20 . The diagnostic agent for pancreatic exocrine function according to  claim 19 , wherein the  13 C- or  14 C-labeled oligosaccharide or polysaccharide is modified at the non-reducing terminal.  
     
     
         21 . The diagnostic agent for pancreatic exocrine function according to any one of  claims 16  to  18 , wherein the  13 C- or  14 C-labeled oligosaccharide or polysaccharide is a cyclic oligosaccharide or polysaccharide.  
     
     
         22 . A diagnostic agent for pancreatic exocrine function comprising a  13 C- or  14 C-labeled inclusion complex or a salt thereof having a cyclodextrin or a modified derivative thereof as a host molecule.  
     
     
         23 . The diagnostic agent for pancreatic exocrine function according to any one of  claims 16  to  22 , wherein the pancreatic exocrine function to be diagnosed is the ability of the pancreas to secrete α-amylase.  
     
     
         24 . The diagnostic agent for pancreatic exocrine function according to any one of  claims 16  to  22 , wherein the pancreatic exocrine function to be diagnosed is the ability of the pancreas to secrete α-amylase and at least one pancreatic exocrine enzyme other than α-amylase.  
     
     
         25 . A  13 C- or  14 C-labeled fluorescein ester compound or a salt thereof.  
     
     
         26 . The compound or salt, thereof according to  claim 25 , which is a compound or salt thereof resulting from a reaction of a  13 C- or  14 C-labeled acid with fluorescein at both or either of the two hydroxyl groups at 3′ and 6′ positions to form an ester linkage.  
     
     
         27 . The compound or salt thereof according to  claim 26 , wherein the acid is a carboxylic acid.  
     
     
         28 . The compound or salt thereof according to  claim 27 , wherein the carboxylic acid is a fatty acid.  
     
     
         29 . The compound or salt thereof according to  claim 28 , wherein the fatty acid has 2 to 16 carbon atoms.  
     
     
         30 . The compound or salt thereof according to  claim 29 , wherein the fatty acid is selected from the group consisting of lauric, acetic and octanoic acids.  
     
     
         31 . The  13 C-labeled fluorescein ester compound or salt thereof according to  claim 25 , which is selected from the group consisting of the following compounds: 
 (a)  13 C-dilaurylfluorescein;    (b)  13 C-diacetylfluorescein; and    (c)  13 C-dioctanoylfluorescein.    
     
     
         32 . A diagnostic agent for pancreatic exocrine function comprising a  13 C- or  14 C-labeled fluorescein ester compound or a pharmaceutically acceptable salt thereof.  
     
     
         33 . The diagnostic agent for pancreatic exocrine function according to  claim 32 , comprising a compound or salt thereof resulting from a reaction of a  13 C- or  14 C-labeled acid with fluorescein at both or either of the two hydroxyl groups at 3′ and 6′ positions to form an ester linkage.  
     
     
         34 . The diagnostic agent for pancreatic exocrine function according to  claim 33 , wherein the acid is a carboxylic acid.  
     
     
         35 . The diagnostic agent for pancreatic exocrine function according to  claim 34 , wherein the carboxylic acid is a fatty acid.  
     
     
         36 . The diagnostic agent for pancreatic exocrine function according to  claim 35 , wherein the fatty acid has 2 to 16 carbon atoms.  
     
     
         37 . The diagnostic agent for pancreatic exocrine function according to  claim 32 , which is selected from the group consisting of the following compounds: 
 (a)  13 C-dilaurylfluorescein;    (b)  13 C-diacetylfluorescein; and    (c)  13 C-dioctanoylfluorescein.    
     
     
         38 . The diagnostic agent for pancreatic exocrine function according to any one of  claims 32  to  37 , wherein the  13 C- or  14 C-labeled fluorescein ester compound or pharmaceutically acceptable salt thereof is subjected to the action of the pancreatic exocrine cholesterol ester hydrolase and pancreatic exocrine esterase and decarboxylated to generate  13 CO 2  or  14 CO 2 .  
     
     
         39 . A  13 C-labelled oligosaccharide or polysaccharide or salt thereof according to any one of  claims 1  to  10  for use in a method of diagnosis.  
     
     
         40 . An inclusion complex according to any of  claims 11  to  15  for use in a method of diagnosis.  
     
     
         41 . A  13 C or  14 C-labelled fluorescein ester compound or salt thereof according to any one of  claims 25  to  31  for use in a method of diagnosis.  
     
     
         42 . A compound according to any one of  claims 39  to  41  wherein the diagnosis is the diagnosis of pancreatic exocrine function.