Claims for Patent: 5,256,684

Summary for Patent: 5,256,684

Title:	Methods and compositions for the treatment of gastrointestinal disorders
Abstract:	Methods, for the treatment of humans and lower animal subjects having a gastrointestinal disorder, comprising administering bismuth and administering an antimicrobial. From about 50 to about 5000 milligrams of bismuth are administered, per day, for from 3 to 56 days. A safe and effective amount of antimicrobial is administered for from 1 to 21 days. Preferred processes also include a step for performing a diagnostic test on the subject for detection of a campylobacter-like organism infection of the subject. The invention also provides compositions containing a safe and effective amount of bismuth and a safe and effective amount of antimicrobial.
Inventor(s):	Marshall; Barry J. (Charlottesville, VA)
Assignee:	The Procter & Gamble Company (Cincinnati, OH)
Application Number:	07/737,573
Patent Claims:	1. A method, for the treatment of a human or lower animal subject having an infectious upper gastrointestinal tract disorder caused or mediated by a Campylobacter pyloridis infection in said subject, comprising administering to said subject a pharmaceutically-acceptable bismuth agent and a pharmaceutically-acceptable antimicrobial agent in amounts safe and effective for combatting the Campylobacter pyloridis infection. 2. A method, according to claim 1, for the treatment of a human or lower animal subject having an infectious upper gastrointestinal tract disorder caused or mediated by Campylobacter pyloridis, comprising administering to said subject from about 50 milligrams to about 5000 milligrams of bismuth, per day, for from 3 to 56 days, and administering to said subject a safe and effective amount of an antimicrobial, per day, for from 1 to 21 days. 3. A method, according to claim 1, wherein said antimicrobial is administered at a level of from about 100 milligrams to about 10,000 milligrams, per day. 4. A method, according to claim 2, wherein said bismuth is administered at a level of from about 500 milligrams to about 1500 milligrams, per day. 5. A method, according to claim 2, for the treatment of a human or lower animal subject having an infectious non-ulcerative upper gastrointestinal tract disorder caused or mediated by Campylobacter pyloridis, wherein said bismuth is administered for from 3 to 21 days. 6. A method, according to claim 2, for the treatment of a human or lower animal subject having an infectious peptic ulcer disease caused or mediated by Campylobacter pyloridis, wherein said bismuth is administered for from 14 to 56 days. 7. A method, according to claim 2, wherein said antimicrobial is administered for from 1 to 14 days. 8. A method, according to claim 3, wherein said antimicrobial is an antibiotic. 9. A method, according to claim 4, wherein said bismuth is selected from the group consisting of bismuth aluminate, bismuth subcarbonate, bismuth subcitrate, bismuth citrate, tripotassium dicitrato bismuthate, bismuth subgalate, bismuth subnitrate, bismuth tartrate, bismuth subsalicylate, and mixtures thereof. 10. A method, according to claim 9, wherein said bismuth is tripotassium dicitrato bismuthate. 11. A method, according to claim 9, wherein said bismuth is bismuth subsalicylate. 12. A method, according to claim 2, wherein said step of administering an antimicrobial is commenced from 1 to 21 days after the commencement of said step of administering bismuth. 13. A method, according to claim 2, comprising the steps of administering said bismuth; followed by administering said antimicrobial. 14. A method, for the treatment of a human or lower animal subject having an infectious upper gastrointestinal tract disorder caused or mediated by Campylobacter pyloridis, comprising the steps of: (a) performing a diagnostic test on said subject for the detection of a Campylobacter pyloridis infection of said subject; and upon obtaining a positive result from said diagnostic test, (b) combatting said Campylobacter pyloridis infection in said subject by administering to said subject a composition comprising a pharmaceutically-acceptable bismuth agent and a composition comprising a pharmaceutically-acceptable antimicrobial agent in amounts to clear said subject of symptoms of said infection. 15. A method, according to claim 14, wherein said bismuth is administered for a period of time ending when said subject is tested with said diagnostic test and a negative result is obtained. 16. A method, for the treatment of a human or lower animal subject having an infectious upper gastrointestinal tract disorder caused or mediated by a Campylobacter pyloridis infection in said subject, comprising administering to said subject a pharmaceutically-acceptable bismuth salt and a pharmaceutically-acceptable antimicrobial agent in amounts safe and effective for combating the Campylobacter pyloridis infection. 17. A method according to claim 16 wherein said pharmaceutically-acceptable bismuth salt is selected from the group consisting of bismuth aluminate, bismuth subcarbonate, bismuth subcitrate, bismuth citrate, tripotassium dicitrato bismuthate, bismuth subgalate, bismuth subnitrate, bismuth tartrate, bismuth subsalicylate, and mixtures thereof. 18. A method according to claim 17 wherein said pharmaceutically-acceptable salt is tripotassium dicitrato bismuthate. 19. A method according to claim 18 wherein said antimicrobial is an antibiotic. 20. A method according to claim 18 wherein said antimicrobial is selected from the group consisting of gentamicin, neomycin, kanamycin, streptomycin, erythromycin, rifampin, penicillin G, penicillin V, ampicillin, amoxycillin, bacitracin, polymyxin, tetracycline, chlortetracycline, oxytetracycline, doxycyline, cephalexin, cephalothin, chloramphenicol, clindamycin, sulfonamides, nitrofurazone, nitrofurantoin, furozolidone, metronidazole, tinidazole, nimorazole, and mixtures thereof. 21. A method according to claim 18 wherein said antimicrobial is selected from amoxicillin, tinidazole, metronidazole, and mixtures thereof. 22. A method according to claim 18 wherein said antimicrobial is metronidazole. 23. A method according to claim 17 wherein said pharmaceutically-acceptable bismuth salt is bismuth subsalicylate. 24. A method according to claim 23 wherein said antimicrobial is an antibiotic. 25. A method according to claim 23 wherein said antimicrobial is selected from the group consisting of gentamicin, neomycin, kanamycin, streptomycin, erythromycin, rifampin, penicillin G, penicillin V, ampicillin, amoxycillin, bacitracin, polymyxin, tetracycline, chlortetracycline, oxytetracycline, doxycyline, cephalexin, cephalothin, chloramphenicol, clindamycin, sulfonamides, nitrofurazone, nitrofurantoin, furozolidone, metronidazole, tinidazole, nimorazole, and mixtures thereof. 26. A method according to claim 25 wherein said antimicrobial is selected from amoxicillin, tinidazole, metronidazole, and mixtures thereof. 27. A method according to claim 26 wherein said antimicrobial is metronidazole. 28. A method, for the treatment of a human or lower animal subject having an infectious non-ulcerative upper gastrointestinal tract disorder caused or mediated by Campylobacter pyloridis, comprising administering to said subject: (a) a safe and effective amount for treating said Campylobacter pyloridis infection of a pharmaceutically-acceptable bismuth salt, wherein said bismuth salt is selected from the group consisting of bismuth aluminate, bismuth subcarbonate, bismuth subcitrate, bismuth citrate, tripotassium dicitrato bismuthate, bismuth subgalate, bismuth subnitrate, bismuth tartrate, bismuth subsalicylate and mixtures thereof; and (b) a safe and effective amount for treating said Campylobacter pyloridis infection of a pharmaceutically-acceptable antimicrobial agent, wherein said antimicrobial agent is selected from the group consisting of gentamicin, neomycin, kanamycin, streptomycin, erythromycin, rifampin, penicillin G, penicillin V, ampicillin, amoxycillin, bacitracin, polymyxin, tetracycline, chlortetracycline, oxytetracycline, doxycyline, cephalexin, cephalothin, chloramphenicol, clindamycin, sulfonamides, nitrofurazone, nitrofurantoin, furozolidone, metronidazole, tinidazole, nimorazole, and mixtures thereof. 29. A method according to claim 28 wherein said bismuth salt is selected from bismuth subsalicylate, tripotassium dicitrato bismuthate, and mixtures thereof, and said antimicrobial agent is selected from amoxicillin, tinidazole, metronidazole, and mixtures thereof. 30. A method, for the treatment of a human or lower animal subject having infectious gastritis caused or mediated by Campylobacter pyloridis infection, comprising administering to said subject: (a) a safe and effective amount for treating said Campylobacter pyloridis infection of a pharmaceutically-acceptable bismuth salt, wherein said bismuth salt is selected from the group consisting of bismuth aluminate, bismuth subcarbonate, bismuth subcitrate, bismuth citrate, tripotassium dicitrato bismuthate, bismuth subgalate, bismuth subnitrate, bismuth tartrate, bismuth subsalicylate and mixtures thereof; and (b) a safe and effective amount for treating said Campylobacter pyloridis infection of a pharmaceutically-acceptable antimicrobial agent, wherein said antimicrobial agent is selected from the group consisting of gentamicin, neomycin, kanamycin, streptomycin, erythromycin, rifampin, penicillin G, penicillin V, ampicillin, amoxycillin, bacitracin, polymyxin, tetracycline, chlortetracycline, oxytetracycline, doxycyline, cephalexin, cephalothin, chloramphenicol, clindamycin, sulfonamides, nitrofurazone, nitrofurantoin, furozolidone, metronidazole, tinidazole, nimorazole, and mixtures thereof. 31. A method according to claim 30 wherein said bismuth salt is selected from bismuth subsalicylate, tripotassium dicitrato bismuthate, and mixtures thereof, and said antimicrobial agent is selected from amoxicillin, tinidazole, metronidazole, and mixtures thereof. 32. A method according to claim 31 comprising administering to said subject bismuth subsalicylate and metronidazole. 33. A method according to claim 31 comprising administering to said subject tripotassium dicitrato bismuthate and metronidazole. 34. A method, for the treatment of a human or lower animal subject having infectious non-ulcerative dyspepsia caused or mediated by Campylobacter pyloridis, comprising administering to said subject: (a) a safe and effective amount for treating said Campylobacter pyloridis infection of a pharmaceutically-acceptable bismuth salt, wherein said bismuth salt is selected from the group consisting of bismuth aluminate, bismuth subcarbonate, bismuth subcitrate, bismuth citrate, tripotassium dicitrato bismuthate, bismuth subgalate, bismuth subnitrate, bismuth tartrate, bismuth subsalicylate and mixtures thereof; and (b) a safe and effective amount for treating said Campylobacter pyloridis infection of a pharmaceutically-acceptable antimicrobial agent, wherein said antimicrobial agent is selected from the group consisting of gentamicin, neomycin, kanamycin, streptomycin, erythromycin, rifampin, penicillin G, penicillin V, ampicillin, amoxycillin, bacitracin, polymyxin, tetracycline, chlortetracycline, oxytetracycline, doxycyline, cephalexin, cephalothin, chloramphenicol, clindamycin, sulfonamides, nitrofurazone, nitrofurantoin, furozolidone, metronidazole, tinidazole, nimorazole, and mixtures thereof. 35. A method according to claim 34 wherein said bismuth salt is selected from bismuth subsalicylate, tripotassium dicitrato bismuthate, and mixtures thereof, and said antimicrobial agent is selected from amoxicillin, tinidazole, metronidazole, and mixtures thereof. 36. A method according to claim 35 comprising administering to said subject bismuth subsalicylate and metronidazole. 37. A method according to claim 35 comprising administering to said subject tripotassium dicitrato bismuthate and metronidazole. 38. A method, for the treatment of a human or lower animal subject having an infectious peptic ulcer disease caused or mediated by Campylobacter pyloridis, comprising administering to said subject: (a) a safe and effective amount for treating said Campylobacter pyloridis infection of a pharmaceutically-acceptable bismuth salt, wherein said bismuth salt is selected from the group consisting of bismuth aluminate, bismuth subcarbonate, bismuth subcitrate, bismuth citrate, tripotassium dicitrato bismuthate, bismuth subgalate, bismuth subnitrate, bismuth tartrate, bismuth subsalicylate and mixtures thereof; and (b) a safe and effective amount for treating said Campylobacter pyloridis infection of a pharmaceutically-acceptable antimicrobial agent, wherein said antimicrobial agent is selected from the group consisting of gentamicin, neomycin, kanamycin, streptomycin, erythromycin, rifampin, penicillin G, penicillin V, ampicillin, amoxycillin, bacitracin, polymyxin, tetracycline, chlortetracycline, oxytetracycline, doxycyline, cephalexin, cephalothin, chloramphenicol, clindamycin, sulfonamides, nitrofurazone, nitrofurantoin, furozolidone, metronidazole, tinidazole, nimorazole, and mixtures thereof. 39. A method according to claim 38 wherein said bismuth salt is selected from bismuth subsalicylate, tripotassium dicitrato bismuthate, and mixtures thereof, and said antimicrobial is selected from amoxicillin, tinidazole, metronidazole, and mixtures thereof. 40. A method according to claim 38, for the treatment of a human or lower animal subject having a duodenal ulcer, comprising administering to said subject bismuth subsalicylate and metronidazole. 41. A method according to claim 38, for the treatment of a human or lower animal subject having a duodenal ulcer, comprising administering to said subject tripotassium dicitrato bismuthate and metronidazole. 42. A method according to claim 38, for the treatment of a human or lower animal subject having a gastric ulcer, comprising administering to said subject bismuth subsalicylate and metronidazole. 43. A method according to claim 38, for the treatment of a human or lower animal subject having a gastric ulcer, comprising administering to said subject tripotassium dicitrato bismuthate and metronidazole. 44. A method for the treatment of a human or lower animal subject having an infectious non-ulcerative upper gastrointestinal tract disorder caused or mediated by Campylobacter pyloridis, by combatting said Campylobacter pyloridis infection in said subject comprising the step of administering to said subject a composition comprising a pharmaceutically-acceptable bismuth agent and a composition comprising a pharmaceutically-acceptable antimicrobial agent in amounts to clear said subject of symptoms of said infection. 45. A method for the treatment of a human or lower animal subject having infectious gastritis caused or mediated by Campylobacter pyloridis, by combatting said Campylobacter pyloridis infection in said subject comprising the step of administering to said subject a composition comprising a pharmaceutically-acceptable bismuth agent and a composition comprising a pharmaceutically-acceptable antimicrobial agent in amounts to clear said subject of symptoms of said infection. 46. A method for the treatment of a human or lower animal subject having infectious non-ulcerative dyspepsia caused or mediated by Campylobacter pyloridis, by combatting said Campylobacter pyloridis infection in said subject comprising the step of administering to said subject a composition comprising a pharmaceutically-acceptable bismuth agent and a composition comprising a pharmaceutically-acceptable antimicrobial agent in amounts to clear said subject of symptoms of said infection. 47. A method for the treatment of a human or lower animal subject having infectious peptic ulcer disease caused or mediated by Campylobacter pyloridis, by combatting said Campylobacter pyloridis infection in said subject comprising the step of administering to said subject a composition comprising a pharmaceutically-acceptable bismuth agent and a composition comprising a pharmaceutically-acceptable antimicrobial agent in amounts to clear said subject of symptoms of said infection. 48. A method for the treatment of a human or lower animal subject having infectious duodenal ulcers caused or mediated by Campylobacter pyloridis, by combatting said Campylobacter pyloridis infection in said subject comprising the step of administering to said subject a composition comprising a pharmaceutically-acceptable bismuth agent and a composition comprising a pharmaceutically-acceptable antimicrobial agent in amounts to clear said subject of symptoms of said infection. 49. A method for the treatment of a human or lower animal subject having infectious gastric ulcers caused or mediated by Campylobacter pyloridis, by combatting said Campylobacter pyloridis infection in said subject comprising the step of administering to said subject a composition comprising a pharmaceutically-acceptable bismuth agent and a composition comprising a pharmaceutically-acceptable antimicrobial agent in amounts to clear said subject of symptoms of said infection.