Medicinal composition for treating urinary tract infection (uti)

Abstract

Provided is a pharmaceutical composition for use in a method of preventing or treating a urinary tract infection (UTI), chronic cystitis, overactive bladder, partial bladder obstruction or urethritis, said composition comprising one or more oligomeric tannins, selected from proanthocyanidins and/or hydrolysable tannins, where in said method said composition is administered intraurethrally, intravesically, intraureterally and/or intrarenally, as well as a pharmaceutical composition for use in a method of preventing or treating bladder cancer, where in said method said composition is administered intravesically, said composition comprising one or more oligomeric tannins, selected from proanthocyanidins and/or hydrolysable tannins, wherein said tannins are optionally bound to an anti-cancer agent and/or liposomes containing an anti-cancer agent, together with compositions related thereto.

What is claimed is: 
     
         1 . A method for treating or inhibiting a urinary tract infection (UTI) in a subject comprising administering to the bladder of a subject in need thereof an effective amount of a composition of oligomeric tannins, selected from proanthocyanidins and hydrolysable tannins, wherein:
 the composition of oligomeric tannins comprises oligomeric tannins having an average degree of polymerization of 4 or greater; the composition is substantially free of monomeric tannin base units and monomeric polyphenols; and   the composition is administered intraurethrally, intravesically, intraureterally and/or intrarenally;   thereby treating or inhibiting the urinary tract infection.   
     
     
         2 . The method of  claim 1  wherein the UTI is a uropathogenic  Escherichia coli  infection. 
     
     
         3 . The method of  claim 1  wherein the oligomeric tannins are hydrolysable tannins. 
     
     
         4 . The method of  claim 1  wherein the oligomeric tannins are proanthocyanidins. 
     
     
         5 . The method of  claim 4  wherein the proanthocyanidins have an average degree of polymerization of 4 to 25. 
     
     
         6 . The method of  claim 4  wherein the proanthocyanidins each have at least one A-type interflavan linkage, and a flavanol/flavan degree of polymerization of 4 to 25 or an average degree of polymerization of 4 to 25. 
     
     
         7 . The method of  claim 1  wherein the composition administered to the subject has a concentration of oligomeric tannins of about 0.3125 microgram per milliliter or greater. 
     
     
         8 . The method of  claim 1  wherein the oligomeric tannins agglutinate pathogenic bacteria and increase clearance of the pathogenic bacteria. 
     
     
         9 . The method of  claim 1  wherein the administration inhibits the invasion of epithelial cells by pathogenic bacteria or inhibits the establishment of persistent or transient bacterial colonies. 
     
     
         10 . The method of  claim 9  wherein the oligomeric tannins increase the barrier integrity between epithelial cells of the bladder, thereby increasing resistance to pathogenic bacterial invasion of epithelial cells. 
     
     
         11 . The method of  claim 1  wherein the composition additionally comprises one or more additional agents selected from the group consisting of an anti-infective agent, an anti-muscarinic agent, an anti-inflammatory agent, an anesthetic, a glycosaminoglycan, and an anti-cancer agent. 
     
     
         12 . The method of  claim 11  wherein, for any additional agent, part or all of the proanthocyanidins are bound to at least part of the additional agent, and/or liposomes containing part or all of the additional agent. 
     
     
         13 . The method of  claim 4  wherein the proanthocyanidins form a web-like prophylactic network on the epithelial surface of the urogenital tract that agglutinates bacteria by entrapment, thereby promoting urothelial impermeability to bacterial adherence or bacterial invasion; 
     
     
         14 . A method for treating or inhibiting a urinary tract infection in a subject comprising administering, intraurethrally, intravesically, intraureterally or intrarenally, to a subject in need thereof an effective amount of a composition comprising oligomeric proanthocyanidins, the oligomeric proanthocyanidin having an average degree of polymerization of 4 or greater; wherein the composition is substantially free of monomeric tannin base units and monomeric polyphenols, thereby treating or inhibiting the urinary tract infection. 
     
     
         15 . The method of  claim 14  wherein the UTI is a uropathogenic  Escherichia coli  infection. 
     
     
         16 . The method of  claim 14  wherein the composition administered to the subject has a concentration of oligomeric proanthocyanidins of 0.3125 microgram per milliliter or greater. 
     
     
         17 . The method of  claim 14  wherein the proanthocyanidins form a web-like prophylactic network on the epithelial surface of the urogenital tract that agglutinates bacteria by entrapment, thereby promoting urothelial impermeability to bacterial adherence or bacterial invasion; 
     
     
         18 . The method of  claim 14  wherein the composition comprising oligomeric proanthocyanidins further comprises one or more hydrolysable tannins. 
     
     
         19 . A method for treating chronic cystitis, overactive bladder, partial bladder obstruction, or urethritis, comprising administering to a subject in need thereof an effective amount of a composition comprising one or more oligomeric tannins, selected from proanthocyanidins and/or hydrolysable tannins, the oligomeric tannins having an average degree of polymerization of 4 or greater; wherein the composition is substantially free of monomeric tannin base units and monomeric polyphenols and the composition is administered intraurethrally, intravesically, intraureterally and/or intrarenally.