Method and compositions for the treatment of H. pylori and dermatitis

• US 5,409,903 A
• Filed: 02/18/1992
• Issued: 04/25/1995
• Est. Priority Date: 02/18/1992
• Status: Expired due to Fees

• Current Assignee: Urecap Corporation
• Original Assignee: Urecap Corporation
• Inventors: Kappas, Attallah, Polak, Robert B.
• Primary Examiner(s): GRIFFIN, RONALD
• Application Number:
  US07/837,332
• Time in Patent Office: 1,162 Days
• Field of Search: 514/925, 514/23, 514/870, 514/865, 128/360, 602/904, 424/402, 424/447, 424/449, 424/451, 424/464, 424/489, 424/499
• US Class Current: 514/23
• CPC Class Codes: A61F 13/8405 Additives, e.g. for odour, disinfectant or pH control
• CPC Class Codes: A61K 31/19 Carboxylic acids, e.g. valproic acid salicylic acid A61K31/60
• CPC Class Codes: A61K 31/7004 Monosaccharides having only carbon, hydrogen and oxygen atoms
• CPC Class Codes: A61K 31/715 Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
• CPC Class Codes: A61K 33/06 Aluminium, calcium or magnesium; Compounds thereof , e.g. clay
• CPC Class Codes: A61K 33/14 Alkali metal chlorides; Alkaline earth metal chlorides
• CPC Class Codes: A61K 33/42 Phosphorus; Compounds thereof
• CPC Class Codes: Y10S 602/904 Film-forming bandage material

Abstract

A method of treating a mammal for the presence or the activity of H. pylori in the gastrointestinal tract is disclosed. The method encompasses orally administering to said mammal a sufficient amount of a scavenging, reacting or inactivating compound to remove bicarbonate ions, ammonium ions or urea which are present in combination with the microorganisms which colonize and infect the gastric mucosa. Such microorganisms have been implicated in gastritis, gastric ulcer disease and as a risk factor in gastric carcinoma.

Also, the invention encompasses a method, utilizing similar compounds, for the treatment or prevention of dermatitis such as diaper rash wherein these compounds are preapplied to the skin or used to treat the diaper prior to use.

Also included are compositions which are used for the methods described above.

Claims

1. A method of treating a mammal to inhibit the presence or activity of H. pylori in the gastrointestinal tract comprising inactivating the H. pylori protective environment by orally administering to said mammal an effective amount of a scavenging, reacting or inactivating compound to remove the bicarbonate ions, ammonium ions or urea which afford the H. pylori protective environment, thereby exposing the H. pylori to deactivation by the acid environment of the gastrointestinal tract.

2. A method according to claim 1, wherein the compound is a chemical salt which reacts with the bicarbonate ions to form an insoluble bicarbonate compound.

3. A method according to claim 2 wherein the chemical salt is a magnesium or calcium compound which reacts with bicarbonate ions to form a water-insoluble calcium or magnesium bicarbonate compound.

4. A method according to claim 1 wherein the compound is an ion exchange material which inactivates ammonium or bicarbonate ions.

5. A method according to claim 1 wherein the compound is selected from the group consisting of a dibasic magnesium phosphate, dialdehyde polysaccharide, calcium acetate, calcium chloride, calcium gluconate, calcium lactate, magnesium chloride, magnesium citrate and zeolite.

6. A method according to claim 5 wherein the compound is a dialdehyde polysaccharide.

7. The method according to claim 5 wherein the zeolite administered is a mixed sodium/potassium zeolite which has ammonium ion selectivity.

8. The method according to claim 7 wherein the zeolite is pretreated with a sodium chloride solution in an amount effective for exchanging potassium ions contained therein for sodium ions.

9. The method according to claim 7 wherein the zeolite is pretreated with a calcium chloride solution in an amount effective for exchanging potassium and sodium ions for calcium ions.

10. The method according to claim 5 wherein the dibasic magnesium phosphate administered is represented by the formula, exclusive of water of hydration,

11. The method according to claim 10 wherein the Mg to PO₄ ratio (x/z) is about 1.1.

12. The method according to claim 5 wherein the compound is administered in combination with a mucoadhesive.

13. A method according to claim 12 wherein the mucoadhesive is selected from the group consisting of sucralfate, polycarbophil, hydroxyethyl methacrylate, polyacrylic acid, carboxymethylcellulose, hydroxypropylcellulose, polyethylene glycol and polyalkyl cyanoacrylate.

14. A method according to claim 5 wherein one or more of the selected compounds is contained within microcapsules, each such microcapsule having a water-insoluble wall permeable to urea, ammonia, water and other small molecules and ions, but impermeable to proteins, polypeptides, dialdehyde polysaccharide, other large molecules and particulate matter.

15. A method of treating a patient for gastrointestinal disease in which H. pylori is suspected as an etiologic agent comprising inactivating the H. pylori protective environment by orally administering to said patient an effective amount of a compound selected from the group consisting of dibasic magnesium phosphate, dialdehyde polysaccharide, calcium acetate, calcium chloride, calcium gluconate, calcium lactate, magnesium chloride, magnesium citrate and zeolite, sufficient to remove the bicarbonate ions, ammonium ions or urea which result in the H. pylori protective environment, thereby exposing the H. pylori to deactivation by the acid environment of the gastrointestinal tract.

16. A method according to claim 15 wherein the gastrointestinal disease is gastric or duodenal ulcer disease.

17. A method according to claim 15 wherein the gastrointestinal disease is gastritis.

18. The method according to claim 15 wherein the compound is administered in combination with a mucoadhesive.

19. A method according to claim 18 wherein the mucoadhesive is selected from the group consisting of sucralfate, polycarbophil, hydroxyethyl methacrylate, polyacrylic acid, carboxymethylcellulose, hydroxypropylcellulose, polyethylene glycol and polyalkyl cyanoacrylate.

20. A method according to claim 15 wherein one or more of the selected compounds is contained within microcapsules, each such microcapsule having a water-insoluble wall permeable to urea, ammonia, water and other small molecules and ions, but impermeable to proteins, polypeptides, dialdehyde polysaccharide, other large molecules and particulate matter.

21. A method of treating or preventing skin rash in a mammal resulting from exposure to the urease, urea, ammonia and/or bicarbonate of urine and feces, comprising:

exposing the skin to a substantially non-irritating compound selected from the group consisting of dibasic magnesium phosphate, dialdehyde polysaccharide and zeolite, which scavenges, reacts with or deactivates the urea, ammonia or bicarbonate.

22. A method according to claim 21 wherein the skin is exposed to the compound by pre-application of said compound to a diaper in an amount effective to prevent or minimize the occurrence or severity of said rash, and wrapping the skin in said diaper.

23. A method according to claim 21 wherein said compound is used in combination with at least one compound selected from the group consisting of calcium acetate, calcium chloride, calcium gluconate, calcium lactate, magnesium chloride and magnesium citrate.

24. An oral pharmaceutical composition for the inhibition of H. pylori which consists essentially of at least one compound selected from the group consisting of dibasic magnesium phosphate and dialdehyde polysaccharide, in combination with at least one compound selected from the group consisting of calcium acetate, calcium chloride, calcium gluconate, calcium lactate, magnesium chloride and magnesium citrate;

said compounds being present in the composition in an amount effective for the inactivation of the H. pylori protective environment in the gastrointestinal tract of a patient in need of such treatment, and

an oral pharmaceutically acceptable carrier therefor.

25. The pharmaceutical composition according to claim 24 in the form of a powder, solution, suspension, slurry, gel, tablet or capsule.

26. A topical composition for the treatment or prevention of skin rash resulting from exposure to the urease, urea, ammonia and/or bicarbonate of urine and feces which consists essentially of at least one compound selected from the group consisting of dibasic magnesium phosphate, dialdehyde polysaccharide and zeolite, and a compound selected from the group consisting of calcium acetate, calcium chloride, calcium gluconate, calcium lactate, magnesium chloride and magnesium citrate;

said compounds being present in the composition in an amount effective to deactivate the urea, ammonia and/or bicarbonate, and

a topical carrier therefor.

27. A composition according to claim 26 in the form of a solution, suspension, slurry, gel, powder, patch, bandage, cloth, paper, ointment or cream.

28. A composition according to claim 26, further comprising a mucoadhesive compound which forms a film essentially impermeable to enzymes and particulate matter, but permeable to gases and water vapor.

29. A composition according to claim 28 wherein the film forming composition is a mucoadhesive material selected from the group consisting of polycarbophil, hydroxyethyl methacrylate, polyacrylic acid, carboxymethylcellulose, hydroxypropylcellulose, polyethylene glycol and polyalkylcyanoacrylate.

30. A composition according to claim 29 in the form of a solution, suspension, slurry, gel, powder, patch, bandage, cloth, paper, ointment or cream.

31. A composition according to claim 26, further comprising a mucoadhesive compound which forms a film which is permeable to gases and water vapor, but essentially impermeable to large molecules, such as enzymes and particulate matter.

32. A composition according to claim 31 wherein the film forming composition is a mucoadhesive material selected from the group consisting of polycarbophil, hydroxyethyl methacrylate, polyacrylic acid, carboxymethylcellulose, hydroxypropylcellulose, polyethylene glycol and polyalkylcyanoacrylate.

33. A diaper comprised of a substrate material in combination with a composition according to claim 26.

34. An oral pharmaceutical composition for the inhibition of H. pylori which consists essentially of a zeolite and at least one compound selected from the group consisting of calcium acetate, calcium chloride, calcium gluconate, calcium lactate, magnesium chloride and magnesium citrate;

said zeolite and said compound being present in the composition in an amount effective for the inactivation of the H. pylori protective environment in the gastrointestinal tract of a patient in need of such treatment, and administered in combination with a mucoadhesive, and an oral pharmaceutically acceptable carrier therefor.

35. An oral pharmaceutical composition for the inhibition of H. pylori which comprises a dialdehyde polysaccharide and at least one compound selected from the group consisting of calcium acetate, calcium chloride, calcium gluconate, calcium lactate, magnesium chloride and magnesium citrate,

said dialdehyde polysaccharide and said compound being present in the composition in an amount effective for the inactivation of the H. pylori protective environment in the gastrointestinal tract of a patient in need of such treatment, and administered in combination with a mucoadhesive, and an oral pharmaceutically acceptable carrier therefor.