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 tablet comprising granules and at least one hydrophilic compound, wherein the granules comprise:
 (a) rifamycin SV;   (b) at least one amphiphilic compound; and   (c) at least one lipophilic compound.   
     
     
         2 . The tablet according to  claim 1 , wherein the at least one hydrophilic compound is selected from the group consisting of a hydroxyalkyl cellulose, an alkyl cellulose, a carboxyalkyl cellulose, a polyvinyl alcohol, a carboxyvinyl polymer, a carboxyvinyl copolymer, a polysaccharide derivative, a hyaluronic acid, a glucuronic acid, a glucosamine and a pectin. 
     
     
         3 . The tablet according to  claim 1 , wherein the at least one hydrophilic compound is a hydroxyalkyl cellulose or a carboxyalkyl cellulose. 
     
     
         4 . The tablet according to  claim 1 , wherein the at least one hydrophilic compound is a hydrophilic copolymeric substance. 
     
     
         5 . The tablet according to  claim 1 , wherein the at least one hydrophilic compound is a hydrogel. 
     
     
         6 . The tablet according to  claim 1 , wherein the at least one amphiphilic compound is selected from the group consisting of lecithin, a sphingomyelin, a phospholipid, a ceramide, an alkyl block copolymer, a salt of a sulphated alkyl acid, a polyoxyethylenated alkyl and a sorbitan derivative. 
     
     
         7 . The tablet according to  claim 1 , wherein the at least one amphiphilic compound is lecithin. 
     
     
         8 . The tablet according to  claim 1 , wherein the at least one lipophilic compound is selected from the group consisting a wax, stearic acid and stearin. 
     
     
         9 . The tablet according to  claim 1 , wherein the at least one lipophilic compound is stearic acid. 
     
     
         10 . The tablet according to  claim 1 , further comprising a gastro-resistant film coating. 
     
     
         11 . The tablet according to  claim 10 , wherein the gastro-resistant film coating comprises acrylic and/or methacrylic acid polymers, or copolymers, or cellulose phthalate derivatives. 
     
     
         12 . The tablet according to  claim 10 , wherein the gastro-resistant film coating comprises acrylic and methacrylic acid copolymers. 
     
     
         13 . A tablet coated with a gastro-resistant film, wherein the gastro-resistant film comprises methacrylic acid polymers and/or copolymers, and the tablet comprises:
 (i) a hydrophilic copolymeric substance; and   (ii) granules in the hydrophilic copolymeric substance, wherein the granules comprise:
 (a) rifamycin SV; 
 (b) lecithin; and 
 (c) stearic acid. 
   
     
     
         14 . A tablet comprising rifamycin SV, at least one amphiphilic compound, at least one lipophilic compound and at least one hydrophilic compound prepared by a process comprising the steps:
 (a) mixing rifamycin SV, at least one amphiphilic compound and at least one lipophilic compound to form a first mixture;   (b) granulating the first mixture to form granules;   (c) mixing the granules with at least one hydrophilic compound to form a second mixture; and   (d) tableting the second mixture to form a tablet.   
     
     
         15 . The tablet according to  claim 14 , wherein the at least one hydrophilic compound is selected from the group consisting of a hydroxyalkyl cellulose, an alkyl cellulose, a carboxyalkyl cellulose, a polyvinyl alcohol, a carboxyvinyl polymer, a carboxyvinyl copolymer, a polysaccharide derivative, a hyaluronic acid, a glucuronic acid, a glucosamine and a pectin. 
     
     
         16 . The tablet according to  claim 14 , wherein the at least one hydrophilic compound is a hydroxyalkyl cellulose or a carboxyalkyl cellulose. 
     
     
         17 . The tablet according to  claim 14  wherein the at least one hydrophilic compound is a hydrophilic copolymeric substance. 
     
     
         18 . The tablet according to  claim 14 , wherein the at least one hydrophilic compound is a hydrogel. 
     
     
         19 . The tablet according to  claim 14 , wherein the at least one amphiphilic compound is selected from the group consisting of lecithin, a sphingomyelin, a phospholipid, a ceramide, an alkyl block copolymer, a salt of a sulphated alkyl acid, a polyoxyethylenated alkyl and a sorbitan derivative. 
     
     
         20 . The tablet according to  claim 14 , wherein the at least one amphiphilic compound is lecithin. 
     
     
         21 . The tablet according to  claim 14 , wherein the at least one lipophilic compound is selected from the group consisting a wax, stearic acid and stearin. 
     
     
         22 . The tablet according to  claim 14 , wherein the at least one lipophilic compound is stearic acid. 
     
     
         23 . The tablet according to  claim 14 , wherein the tablet further comprises a gastro-resistant film coating prepared by (e) coating the tablet of step (d). 
     
     
         24 . The tablet according to  claim 23 , wherein the gastro-resistant film coating comprises acrylic and/or methacrylic acid polymers, or copolymers, or cellulose phthalate derivatives. 
     
     
         25 . The tablet according to  claim 23 , wherein the gastro-resistant film coating comprises acrylic and methacrylic acid copolymers. 
     
     
         26 . A tablet comprising rifamycin SV, at least one amphiphilic compound, at least one lipophilic compound and at least one hydrophilic compound prepared by a process comprising the steps:
 (a) mixing rifamycin SV and at least one amphiphilic compound to form a first mixture;   (b) mixing the first mixture with the at least one lipophilic compound to form a second mixture;   (c) mixing the second mixture with the at least one hydrophilic compound to form a third mixture; and   (d) tableting the third mixture to form a tablet.   
     
     
         27 . The tablet according to  claim 26 , wherein the at least one hydrophilic compound is selected from the group consisting of a hydroxyalkyl cellulose, an alkyl cellulose, a carboxyalkyl cellulose, a polyvinyl alcohol, a carboxyvinyl polymer, a carboxyvinyl copolymer, a polysaccharide derivative, a hyaluronic acid, a glucuronic acid, a glucosamine and a pectin. 
     
     
         28 . The tablet according to  claim 26 , wherein the at least one hydrophilic compound is a hydroxyalkyl cellulose or a carboxyalkyl cellulose. 
     
     
         29 . The tablet according to  claim 26  wherein the at least one hydrophilic compound is a hydrophilic copolymeric substance. 
     
     
         30 . The tablet according to  claim 26 , wherein the at least one hydrophilic compound is a hydrogel. 
     
     
         31 . The tablet according to  claim 26 , wherein the at least one amphiphilic compound is selected from the group consisting of lecithin, a sphingomyelin, a phospholipid, a ceramide, an alkyl block copolymer, a salt of a sulphated alkyl acid, a polyoxyethylenated alkyl and a sorbitan derivative. 
     
     
         32 . The tablet according to  claim 26 , wherein the at least one amphiphilic compound is lecithin. 
     
     
         33 . The tablet according to  claim 26 , wherein the at least one lipophilic compound is selected from the group consisting a wax, stearic acid and stearin. 
     
     
         34 . The tablet according to  claim 26 , wherein the at least one lipophilic compound is stearic acid. 
     
     
         35 . The tablet according to  claim 26 , wherein the tablet further comprises a gastro-resistant film coating prepared by (e) coating the tablet of step (d). 
     
     
         36 . The tablet according to  claim 35 , wherein the gastro-resistant film coating comprises acrylic and/or methacrylic acid polymers, or copolymers, or cellulose phthalate derivatives. 
     
     
         37 . The tablet according to  claim 35 , wherein the gastro-resistant film coating comprises acrylic and methacrylic acid copolymers. 
     
     
         38 . A method of treating a pathological condition of the colon comprising administering to a patient in need thereof the controlled release oral pharmaceutical composition according to  claim 1 , wherein the pathological condition is infectious colitis, bacillary dysentery, pseudomembranous colitis, travellers' diarrhoea, diverticular disease and/or diverticulitis. 
     
     
         39 . A method of treating a pathological condition of the colon comprising administering to a patient in need thereof the controlled release oral pharmaceutical composition according to  claim 1 , wherein the pathological condition is travellers' diarrhoea. 
     
     
         40 . A method of treating a pathological condition of the colon comprising administering to a patient in need thereof the controlled release oral pharmaceutical composition according to  claim 1 , wherein the pathological condition is diverticular disease and/or diverticulitis. 
     
     
         41 . A method of treating a pathological condition of the colon comprising administering to a patient in need thereof the controlled release oral pharmaceutical composition according to  claim 13 , wherein the pathological condition is infectious colitis, bacillary dysentery, pseudomembranous colitis, travellers' diarrhoea, diverticular disease and/or diverticulitis. 
     
     
         42 . A method of treating a pathological condition of the colon comprising administering to a patient in need thereof the controlled release oral pharmaceutical composition according to  claim 13 , wherein the pathological condition is travellers' diarrhoea. 
     
     
         43 . A method of treating a pathological condition of the colon comprising administering to a patient in need thereof the controlled release oral pharmaceutical composition according to  claim 13 , wherein the pathological condition is diverticular disease and/or diverticulitis. 
     
     
         44 . A method of treating a pathological condition of the colon comprising administering to a patient in need thereof the controlled release oral pharmaceutical composition according to  claim 14 , wherein the pathological condition is infectious colitis, bacillary dysentery, pseudomembranous colitis, travellers' diarrhoea, diverticular disease and/or diverticulitis. 
     
     
         45 . A method of treating a pathological condition of the colon comprising administering to a patient in need thereof the controlled release oral pharmaceutical composition according to  claim 14 , wherein the pathological condition is travellers' diarrhoea. 
     
     
         46 . A method of treating a pathological condition of the colon comprising administering to a patient in need thereof the controlled release oral pharmaceutical composition according to  claim 14 , wherein the pathological condition is diverticular disease and/or diverticulitis. 
     
     
         47 . A method of treating a pathological condition of the colon comprising administering to a patient in need thereof the controlled release oral pharmaceutical composition according to  claim 26 , wherein the pathological condition is infectious colitis, bacillary dysentery, pseudomembranous colitis, travellers' diarrhoea, diverticular disease and/or diverticulitis. 
     
     
         48 . A method of treating a pathological condition of the colon comprising administering to a patient in need thereof the controlled release oral pharmaceutical composition according to  claim 26 , wherein the pathological condition is travellers' diarrhoea. 
     
     
         49 . A method of treating a pathological condition of the colon comprising administering to a patient in need thereof the controlled release oral pharmaceutical composition according to  claim 26 , wherein the pathological condition is diverticular disease and/or diverticulitis.