Oral antimicrobial pharmaceutical compositions

Abstract

The present invention relates to oral pharmaceutical compositions with controlled and/or programmed release containing at least one active ingredient having antimicrobial and/or anti-infectious activity for the treatment of infections of the large intestine, in particular the colon.

1 . A method of treating an infection of the large intestine in a patient, comprising administering to said patient a pharmaceutical composition comprising:
 (1) a tablet core comprising a homogenous structure comprising:
 (a) a therapeutically effective amount of rifamycin SV; 
 (b) at least one hydrophilic substance; 
 (c) at least one lipophilic substance; and 
 (d) optionally at least one amphiphilic substance; and 
   (2) a coating on said tablet core, said coating comprising a gastro-resistant substance.   
     
     
         2 . The method of  claim 1 , wherein said at least one hydrophilic substance is from at least one of carboxyvinyl polymers, carboxyvinyl copolymers, hydroxyalkyl celluloses, alkyl celluloses, carboxyalkyl celluloses, polysaccharides, pectins, hyaluronic acid, glucuronic acid and glucosamines. 
     
     
         3 . The method of  claim 2 , wherein said at least one hydrophilic substance is chosen from at least one of carboxyvinyl polymers and carboxyvinyl copolymers. 
     
     
         4 . The method of  claim 1 , wherein said at least one lipophilic substance has a melting point less than about 90° C. 
     
     
         5 . The method of  claim 4 , wherein said at least one lipophilic substance is selected from stearic acid, beeswax, carnuba wax, palmitic acid, and palmitostearate. 
     
     
         6 . The method of  claim 1 , wherein said at least one amphiphilic substance is selected from the group consisting of lecithin, polyoxyethylenated sorbitan monooleate, sodium lauryl sulfate, sodium dioctyl sulphosuccinate, and ethylene and/or propylene block copolymers. 
     
     
         7 . The method of  claim 1 , wherein said coating on said tablet core is selected from acrylic and methacrylic acid esters and/or cellulose phthalate. 
     
     
         8 . The method of  claim 1 , wherein:
 (a) said at least one hydrophilic substance is selected from at least one of carboxyvinyl polymers, carboxyvinyl copolymers, hydroxyalkyl celluloses, alkyl celluloses, carboxyalkyl celluloses, polysaccharides, pectins, hyaluronic acid, glucuronic acid and glucosamines; and   (b) said at least one lipophilic substance has melting point less than about 90° C.   
     
     
         9 . The method of  claim 8 , wherein said at least one amphiphilic substance is lecithin. 
     
     
         10 . The method of  claim 1 , wherein said rifamycin SV is in the form of a sodium salt. 
     
     
         11 . The method of  claim 1 , wherein said pharmaceutical composition comprises from about 10% to about 90% by weight of said rifamycin SV. 
     
     
         12 . The method of  claim 1 , wherein said pharmaceutical composition comprises from about 20% to about 60% by weight of said rifamycin SV. 
     
     
         13 . The method of  claim 1 , wherein said pharmaceutical composition comprises from about 1% to about 3.4% by weight of said at least one lipophilic substance. 
     
     
         14 . The method of  claim 1 , wherein said pharmaceutical composition comprises from about 8.4% to about 23% by weight of said at least one hydrophilic substance. 
     
     
         15 . The method of  claim 1 , wherein said pharmaceutical composition comprises:
 (a) from about 10% to about 90% by weight of said rifamycin SV;   (b) from about 1% to about 3.4% by weight of said at least one lipophilic substance; and   (c) from about 8.4% to about 23% by weight of said at least one hydrophilic substance.   
     
     
         16 . The method of  claim 1 , wherein said pharmaceutical composition is resistant to dissolution for 2 hours in an environment at pH 1. 
     
     
         17 . The method of  claim 1 , wherein said pharmaceutical composition is resistant to dissolution for 1 hour in an environment at pH 6.4. 
     
     
         18 . The method of  claim 1 , wherein said infection of the large intestine in said patient is infectious colitis, bacillary dysentery, pseudomembranous colitis, diarrhea, or diverticulitis. 
     
     
         19 . The method of  claim 18 , wherein said infection of the large intestine in said patient is diarrhea. 
     
     
         20 . The method of  claim 19 , wherein said infection of the large intestine in said patient is traveler's diarrhea.