This invention relates to compositions of matter useful as anti-diarrheal agents and to the method of controlling and treating diarrhea in warm blooded animals. The active anti-diarrheal agents are substituted anilino nicotinic acids, and salts thereof and ester and hydrazine derivatives of said acids.

Schering Corporation

Anti-diarrheal anilino nicotinic acids and method of using same

Pharmaceutical compositions containing an effective amount of a ligand for GPR109 to decrease intracellular cAMP levels of a subject in combination with an effective amount of a DNA methyl transferase inhibito to reduce or inhibit downregulation of GPR109 in the intestinal epithelial cells of the subject relative to a control are provided. It has been discovered that ligands for GPR109 can be used to treat one or more symptoms of cancer, inflammatory disorders, and diarrhea. Representative CPR109 ligands include, but are not limited to butyrate, .beta.-hydroxybutyrate, nicotinic acid, acifran, and octanoate. Suitable DNA methyl transferase inhibitors include 5-azacytidine, 5-aza-2'-deoxytidine, 1-.beta.-D-arabinfarnosyl-5-azacytosine and dihydro-5-azacytidine. Typically, the compositions are formulated to achieve a GPR109 ligand serum blood level of about 1 to about 1000 .mu.M. The compositions are useful for the treatment of one or more symptoms of cancer. Preferred cancers that can be treated using the disclosed compositions include, but are not limited to colon cancer, breast cancer and leukemia. Methods for treating cancer, inflammatory disorders, and diarrhea are also provided.

nicotinic acid/hnačka

Anti-diarrheal anilino nicotinic acids and method of using same

Compositions comprising a GPR109 ligand for treating disorders of the digestive tract and/or cancer

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