Treatment of helicobacter with isothiocyanates

• US 20020151505A1
• Filed: 08/21/2001
• Published: 10/17/2002
• Est. Priority Date: 08/21/2000
• Status: Active Grant

• Current Assignee: Jed W. Fahey
• Original Assignee: Jed W. Fahey
• Inventors: Fahey, Jed W.
• Granted Patent: US 6,737,441 B2
• Time in Patent Office: Days
• US Class Current: 514/23
• CPC Class Codes: A23L 33/10 using additives addition of substantially indigestible substances A23L33/21
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/26 Cyanate or isocyanate esters; Thiocyanate or isothiocyanate esters
• CPC Class Codes: A61K 31/43 Compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula , e.g. penicillins, penems
• CPC Class Codes: A61K 31/7024 Esters of saccharides
• CPC Class Codes: A61K 31/7048 having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin , digitoxin or digoxin
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 35/00 Antineoplastic agents

Abstract

The present invention relates to methods of preventing or inhibiting the growth of Helicobacter through the use of a composition that comprises a glucosinolate, an isothiocyanate or a derivative or metabolite thereof. The present invention also relates to methods of preventing or treating persistent chronic gastritis, ulcers and/or stomach cancer in subjects at risk for, or in need of treatment thereof.

Claims

1. A method of treating a subject having a Helicobacter infection, comprising administering an antibacterially effective amount of a composition to said subject, said composition comprising a glucosinolate, an isothiocyanate or a derivative thereof.

2. The method of claim 1, wherein said isothiocyanate is sulforaphane, sulforaphene, erysolin, erucin, iberin, alyssin, berteroin, iberverin, cheirolin, 5-methylsulfinylpentyl isothiocyanate, 6-methylsulfinylhexyl isothiocyanate, 7-methylsulfinylheptyl isothiocyanate, 8-methylsulfinyloctyl isothiocyanate, 9-methylsulfinyinonyl isothiocyanate, 10-methylsulfinyidecyl isothiocyanate, phenylethyl isothiocyanate, 4-(α

-L-rhamnopyranosyloxy)benzyl isothiocyanate, 3-(α

-L rhamnopyranosyloxy)benzyl isothiocyanate, 2-(α

-L-rhamnopyranosyloxy)benzyl isothiocyanate, 4-(4′

-O-acetyl-α

-L-rhamnopyranosyloxy)benzyl isothiocyanate or a derivative thereof.

3. The method of claim 2, wherein said isothiocyanate is sulforaphane.

4. The method of claim 1, wherein said composition is a food, food supplement, a dietary supplement or food additive.

5. The method of claim 4, wherein said composition comprises a glucosinolate or a derivative thereof.

6. The method of claim 1, wherein said composition is a pharmaceutical composition.

7. The method of claim 6, wherein said pharmaceutical composition is administered orally.

8. The method of claim 1, wherein said subject having a Helicobacter infection is suffering from an ulcer.

9. The method of claim 1, wherein said subject is suffering from, or at risk for developing stomach cancer.

10. The method of claim 1, wherein said Helicobacter is Helicobacter pylori.

11. The method of claim 1, further comprising administering an antibiotic to said subject.

12. The method of claim 11, wherein said antibiotic is selected from the group consisting of amoxycillin and clarithromycin.

14. The method of claim 13, wherein said isothiocyanate is sulforaphane, sulforaphene, erysolin, erucin, iberin, alyssin, berteroin, iberverin, cheirolin, 5-methylsulfinylpentyl isothiocyanate, 6-methylsulfinylhexyl isothiocyanate, 7-methylsulfinylheptyl isothiocyanate, 8-methylsulfinyloctyl isothiocyanate, 9-methylsulfinyinonyl isothiocyanate, 10-methylsulfinyidecyl isothiocyanate, phenylethyl isothiocyanate, 4-(α

-L-rhamnopyranosyloxy)benzyl isothiocyanate, 3-(α

-L-rhamnopyranosyloxy)benzyl isothiocyanate, 2-(α

-L-rhamnopyranosyloxy)benzyl isothiocyanate, 4-(4′

-O-acetyl-α

-L-rhamnopyranosyloxy)benzyl isothiocyanate or a derivative thereof.

15. The method of claim 14, wherein said isothiocyanate is sulforaphane.

16. The method of claim 13, wherein said Helicobacter is Helicobacter pylori.

17. The method of claim 13, wherein said composition is a food, food supplement, dietary supplement or a food additive.

18. The method of claim 17, wherein wherein said composition comprises a glucosinolate or a derivative thereof.

19. The method of claim 13, wherein said composition is a pharmaceutical composition.

20. The method of claim 19, wherein said pharmaceutical composition is administered orally.

13. A method of preventing a Helicobacter infection in a subject, comprising treating said subject with an antibacterially effective amount of a composition, said composition comprising a glucosinolate, an isothiocyanate or a derivative thereof.

21. A method for inhibiting the growth of Helicobacter, comprising administering to said Helicobacter an antibacterially effective amount of an agent selected from the group consisting of a glucosinolate, an isothiocyanate or a derivative thereof.

22. The method of claim 21, wherein said isothiocyanate is sulforaphane, sulforaphene, erysolin, erucin, iberin, alyssin, berteroin, iberverin, cheirolin, 5-methylsulfinylpentyl isothiocyanate, 6-methylsulfinylhexyl isothiocyanate, 7-methylsulfinylheptyl isothiocyanate, 8-methylsulfinyloctyl isothiocyanate, 9-methylsulfinyinonyl isothiocyanate, 10-methylsulfinyldecyl isothiocyanate, phenylethyl isothiocyanate, 4-(α

-L-rhamnopyranosyloxy)benzyl isothiocyanate, 3-(α

-L-rhamnopyranosyloxy)benzyl isothiocyanate, 2-(α

-L-rhamnopyranosyloxy)benzyl isothiocyanate, 4-(4′

-O-acetyl-α

-L-rhamnopyranosyloxy)benzyl isothiocyanate or a derivative thereof.

23. The method of claim 21, wherein said isothiocyanate is sulforaphane.

24. The method of claim 21, wherein said Helicobacter is Helicobacter pylori.

25. The method of claim 21, wherein said agent is administered as a composition.

26. The method of claim 25, wherein said composition is a food, a food supplement, dietary supplement or a food additive.

27. The method of claim 26, wherein said composition comprises a glucosinolate or a derivative thereof.

28. The method of claim 25, wherein said composition is a pharmaceutical composition.

29. The method of claim 21, further comprising administering an antibiotic to said Helicobacter.

30. The method of claim 29, wherein said antibiotic is selected from the group consisting of amoxycillin and clarithromycin.

31. A method of identifying an agent that modulates the growth of Helicobacter comprising

a. treating Helicobacter with said agent and assaying for growth of said Helicobacter;

b. treating said Helicobacter with a known modulator of Helicobacter growth and assaying for growth of said Helicobacter, wherein said known modulator of Helicobacter growth is selected from the group consisting of an isothiocyanate, a glucosinolate and a derivative thereof; and

c. comparing the levels of Helicobacter growth in (a) and (b) to determine if said agent modulates said growth of Helicobacter.

32. The method of claim 31, wherein said isothiocyanate is sulforaphane, sulforaphene, erysolin, erucin, iberin, alyssin, berteroin, iberverin, cheirolin, 5-methylsulfinylpentyl isothiocyanate, 6-methylsulfinylhexyl isothiocyanate, 7-methylsulfinylheptyl isothiocyanate, 8-methylsulfinyloctyl isothiocyanate, 9-methylsulfinyinonyl isothiocyanate, 10-methylsulfinyldecyl isothiocyanate, phenylethyl isothiocyanate, 4-(α

-L-rhamnopyranosyloxy)benzyl isothiocyanate, 3-(α

-L-rhamnopyranosyloxy)benzyl isothiocyanate, 2-(α

-L-rhamnopyranosyloxy)benzyl isothiocyanate, 4-(4′

-O-acetyl-α

-L-rhamnopyranosyloxy)benzyl isothiocyanate or a derivative thereof.

33. The method of claim 32, wherein said isothiocyanate is sulforaphane.

34. The method of claim 31, wherein (b) is performed on said Helicobacter in (a) after said agent in (a) is removed.

35. The method of claim 31, wherein said Helicobacter is Helicobacter pylori.

36. The method of claim 31, wherein said Helicobacter occurs in or around animal cells.

37. The method of claim 31, wherein said method is performed in vivo.

38. The method of claim 31, wherein said method is performed in vitro.