Use of urocanic acid being able to acidify the cell cytoplasm and for preventing or halting cellular proliferation in a person

Abstract

The use of urocanic acid or another pharmaceutically acceptable agent being able to acidify the cell cytoplasm, for the manufacture of a pharmaceutical composition useful for causing inhibition or halting of transformed or non-transformed cell proliferation in a person or an animal, where an effective amount of the agent is administered in an essentially non-dissociated form to the person or animal. The use of the agent as an enhancer for other therapeutically active agents, and a pharmaceutical composition, are also disclosed.

1 - 15 . (canceled)  
   
   
       16 . A method for preventing or halting cellular proliferation in a person or an animal, comprising administering an effective amount of said cis-urocanic acid in an essentially non-dissociated form to the person or animal in the form of a pharmaceutical composition.  
   
   
       17 . The method of  claim 16 , wherein said cis-urocanic acid has a dissociation constant in the range of 5.0 to 7.4.  
   
   
       18 . The method of  claim 17 , wherein said dissociation constant is in the range of 6.0 to 7.3.  
   
   
       19 . The method of  claim 18 , wherein said dissociation constant is about 7.0.  
   
   
       20 . The method of  claim 16 , wherein said person or animal is in need of treatment or prevention of a disease or disorder which is curable by intracellular acidification inducing the inhibition or halting of cell proliferation.  
   
   
       21 . The method of  claim 20 , wherein the disease or disorder is a local or systemic, non-transformed or transformed hyperproliferative disease.  
   
   
       22 . The method of  claim 21 , wherein the disease or disorder is a local or systemic cancer selected from brain, lung, skin, bladder, gastric, pancreatic, breast, head, neck, kidney, ovarian, prostate, colorectal, oesophageal, gynaecological and thyroid cancer.  
   
   
       23 . The method of  claim 16 , wherein the cis-urocanic acid is administered systemically or locally.  
   
   
       24 . The method of  claim 23 , wherein said cis-urocanic acid is administered locally.  
   
   
       25 . The method of  claim 24 , wherein said cis-urocanic acid is administered topically.  
   
   
       26 . A method for enhancing the effect of a therapeutically active agent, comprising administering said therapeutically active agent to a human or animal in need of said treatment in combination with cis-urocanic acid.  
   
   
       27 . Pharmaceutical composition comprising a therapeutically active agent, an enhancer for said agent and a pharmaceutically acceptable agent being able to acidify the cell cytoplasm, in combination with a pharmaceutically acceptable carrier, which carrier essentially prevents the enhancer from dissociating at extracellular pH values.  
   
   
       28 . The composition of  claim 27 , wherein said enhancer is an agent having its dissociation constant in the range 5.0 to 7.4.  
   
   
       29 . The composition of  claim 28 , wherein said dissociation constant is in the range 6.0 to 7.3.  
   
   
       30 . The composition of  claim 29 , wherein said dissociation constant is about 7.0.  
   
   
       31 . The composition of  claim 27 , wherein said enhancer is trans-urocanic acid.  
   
   
       32 . The composition of  claim 27 , wherein said enhancer is cis-urocanic acid.  
   
   
       33 . The composition of  claim 27 , wherein the therapeutically active agent is an anti-proliferative or anticancer agent.