Topical oral dosage forms containing bismuth compounds

Abstract

Topical oral dosage forms containing bismuth compounds are described, which are useful for treating H. pylori and other bacterial infections that cause gastrointestinal disorders and halitosis, as well as for treating ocular and dermal wounds. Methods of employing topical oral dosage forms for treating bacterial infections that cause gastrointestinal disorders and halitosis, and for treating ocular and dermal wounds, are also described.

1 . A topical oral dosage form comprising a pharmaceutically active agent effective against bacteria in an oral cavity which causes halitosis, wherein the pharmaceutically active agent comprises a bismuth compound, and wherein the topical oral dosage form provides controlled release of the bismuth compound into saliva in the oral cavity for at least 5 minutes in a concentration in the saliva of at least 2 μg/mL.  
   
   
       2 . The topical oral dosage form of  claim 1  wherein the bismuth compound is selected from the group consisting of colloidal bismuth subcitrate, bismuth subcitrate, bismuth citrate, bismuth salicylate, bismuth subsalicylate, bismuth subnitrate, bismuth subcarbonate, bismuth tartrate, bismuth subgallate, tripotassium dicitrato bismuthate, bismuth aluminate, bismuth polysulfates, bismuth polyhydroxy compounds, alpha-D-glucopyranoside bismuth complex, beta-D-fructofuranosyl-oktakis (hydrogen sulfate) bismuth complex, L-dihydro ascorbyl-tetrakis (hydrogen sulfate) bismuth complex, bismuth ascorbyl sulfate, bismuth subascorbate, bismuth sucrose sulfate, bismuth cyclodextrin sulfate, and combinations thereof.  
   
   
       3 . The topical oral dosage form of  claim 1  wherein the bismuth compound is selected from the group consisting of colloidal bismuth subcitrate, bismuth subcitrate, bismuth citrate, bismuth salicylate, bismuth subsalicylate, bismuth subnitrate, bismuth subcarbonate, bismuth tartrate, bismuth subgallate, tripotassium dicitrato bismuthate, bismuth aluminate, and combinations thereof.  
   
   
       4 . The topical oral dosage form of  claim 1  wherein the bismuth compound is selected from the group consisting of bismuth polysulfates, bismuth polyhydroxy compounds, alpha-D-glucopyranoside bismuth complex, beta-D-fructofuranosyl-oktakis (hydrogen sulfate) bismuth complex, L-dihydro ascorbyl-tetrakis (hydrogen sulfate) bismuth complex, bismuth ascorbyl sulfate, bismuth subascorbate, bismuth sucrose sulfate, bismuth cyclodextrin sulfate, and combinations thereof.  
   
   
       5 . The topical oral dosage form of  claim 1  wherein the dosage form is selected from the group consisting of chewing gum, chewable tablets, lozenges, troches, toothpastes, gargling gels, mouth rinses, and combinations thereof.  
   
   
       6 . The topical oral dosage form of  claim 1  wherein the dosage form is selected from the group consisting of chewing gum, chewable tablets, lozenges, troches, and combinations thereof.  
   
   
       7 . The topical oral dosage form of  claim 1  wherein the dosage form is a chewing gum.  
   
   
       8 . The topical oral dosage form of  claim 1  wherein the dosage form is a chewable tablet.  
   
   
       9 . The topical oral dosage form of  claim 1  wherein the dosage form is a lozenge.  
   
   
       10 . The topical oral dosage form of  claim 1  wherein the dosage form is a troche.  
   
   
       11 . The topical dosage form of  claim 1  wherein the bismuth compound is colloidal bismuth subcitrate and the topical dosage form is chewing gum.  
   
   
       12 . The topical dosage form of  claim 11  wherein the chewing gum comprises between about 10 mg and about 200 mg of colloidal bismuth subcitrate.  
   
   
       13 . The topical dosage form of  claim 11  wherein the chewing gum comprises between about 10 mg and about 100 mg of colloidal bismuth subcitrate.  
   
   
       14 . The topical dosage form of  claim 11  wherein the chewing gum comprises between about 10 mg and about 50 mg of colloidal bismuth subcitrate.  
   
   
       15 . The topical dosage form of  claim 1  wherein the controlled release of the bismuth compound in the oral cavity is in an amount of at least ten times the minimum inhibitory concentration for  Helicobacter Pylori.    
   
   
       16 . The topical dosage form of  claim 1  wherein the dosage form is selected from the group consisting of toothpaste, an aerosol, a gargling gel, and a mouth rinse, and wherein the dosage form further comprises a film forming polymer.  
   
   
       17 . The topical dosage form of  claim 1  wherein the dosage form is selected from the group consisting of a chewable tablet and a troche, and wherein the dosage form further comprises a hydrophilic polymer.  
   
   
       18 . The topical dosage form of  claim 1 , further comprising a pharmaceutically effective amount of metronidazole.  
   
   
       19 . The topical dosage form of  claim 1 , further comprising an anti-plaque agent.  
   
   
       20 . The topical dosage form of  claim 19  wherein said anti-plaque agent is selected from the group consisting of glucanase anhydroglucosidase, glucose oxidase, silicon oil, and sanguinarine.  
   
   
       21 . A topical oral dosage form selected from the group consisting of chewing gum, chewable tablets, lozenges, dental paints, viscous gels, dental implants, polymer film adhesives, troches, toothpastes, gargling gels, mouth rinses, and combinations thereof, wherein the topical oral dosage form comprises an effective amount of a pharmaceutically active anti-bacterial agent consisting essentially of a bismuth compound selected from the group consisting of colloidal bismuth subcitrate, bismuth subcitrate, bismuth citrate, bismuth salicylate, bismuth subsalicylate, bismuth subnitrate, bismuth subcarbonate, bismuth tartrate, bismuth subgallate, tripotassium dicitrato bismuthate, bismuth aluminate, bismuth polysulfates, bismuth polyhydroxy compounds, alpha-D-glucopyranoside bismuth complex, beta-D-fructofuranosyl-oktakis (hydrogen sulfate) bismuth complex, L-dihydro ascorbyl-tetrakis (hydrogen sulfate) bismuth complex, bismuth ascorbyl sulfate, bismuth subascorbate, bismuth sucrose sulfate, bismuth cyclodextrin sulfate, and combinations thereof, wherein the topical oral dosage form provides controlled release of the bismuth compound into the saliva in the oral cavity for at least 5 minutes in a concentration in the saliva of at least 2 μg/mL.  
   
   
       22 . The topical oral dosage form of  claim 21  wherein the bismuth compound is colloidal bismuth subcitrate and the topical dosage form is chewing gum.  
   
   
       23 . The topical oral dosage form of  claim 21 , further comprising an effective amount of an antibiotic compound.  
   
   
       24 . The topical oral dosage form of  claim 21  wherein the antibiotic compound is selected from the group consisting of Tetracycline, Amoxicillin, Ampicillin, Doxycycline, Erythromycin, Clarithromycin, Metronidazole, Tinidazole, Ciproflaxacin, Oflaxacin, Norflaxacin, Furazolidine, Nitrofurantoin, and combinations thereof.