Use of at least one glycoinhibitor substance

• US 20040176320A1
• Filed: 12/29/2003
• Published: 09/09/2004
• Est. Priority Date: 06/29/2001
• Status: Abandoned Application

• Current Assignee: Biotie Therapies Copr.
• Original Assignee: Biotie Therapies Copr.
• Inventors: Natunen, Jari, Karlsson, Karl-Anders, Miller-Podraza, Halina, Angstrom, Jonas, Teneberg, Susann
• Application Number:
  US10/482,045
• Publication Number:
  US 20040176320A1
• Time in Patent Office: Days
• US Class Current: 514/54
• CPC Class Codes: A61K 31/7028 Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
• CPC Class Codes: A61K 31/739 Lipopolysaccharides
• CPC Class Codes: A61P 1/02 Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
• 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 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 1/18 for pancreatic disorders, e.g. pancreatic enzymes
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 3/02 Nutrients, e.g. vitamins, minerals
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/10 Antimycotics
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 31/16 for influenza or rhinoviruses
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The present invention relates to the use of a glycosidase inhibitor for the manufacture of a medicament for the treatment of a disease, wherein glycosidase enzymes hydrolyze glycoconjugates of a patient to reveal neutral glycan receptors of an pathogenic agent, and wherein the revealed neutral glycan receptor comprise a oligosaccharide sequence.

Claims

1. Use of at least one glycoinhibitor monosaccharide substance comprising a pyranose formed ring structure selected from the group consisting of GlcNAcβ

, GalNAcβ

, Galβ

, Galα

, GalNAcα

, Fucα

, Manα

, and Neu5Acα

, wherein said monosaccharide substance is linked to a aglycon, for the manufacture of a medicament for the treatment of an infectious disease.

2. The use according to claim 1, wherein said aglycon is a monosaccharide mimicking structure.

3. The use according to claim 2, wherein said monosaccharide mimicking structure is a polyhydroxyl substance.

4. The use according to claim 1, wherein said aglycon is a hydrophilic linker.

5. The use according to claim 1, wherein said aglycon is a non monosaccharide spacer linking said glycoinhibitor to a carrier.

6. The use according to claim 1, wherein said glycoinhibitor monosaccharide substance comprising a pyranose formed ring structure is selected from the group consisting of GlcNAcβ

, GalNAcβ

, Galα

, GalNAcα

, Fucα

, Manα

, and Neu5Acα

.

7. The use according to any one of claims 1-6, wherein at least one oligosaccharide sequence according to Formula

[Galβ

y]_p[Hex(NAc)_rα

/β

z]_sGalβ

4Glc(NAc)_u  

 

(I)

wherein p, r, s, and u are each independently 0 or 1, and y is either linkage position 3 or 4, and z is either linkage position 3 or 4, and Hex is either Gal or Glc, so that when p is 1 and y=3, then Hex is Galβ

or Glcβ and

r=1, or p is 1 and y=4 then Hex is Glcβ and

r=1, when p is 0 and z is 4, then Hex is Galβ and

r is 1 or Hex is Galα and

r is 0, is further used with said glycoinhibitor monosaccharide substance for the manufacture of a medicament for the treatment of an infectious disease.

8. The use according to any one of previous claims, wherein the glycoinhibitor monosaccharide substance is glycosically N-, S-, or C-linked.

9. The use according to any one of the claims 1-8, wherein the glycoinhibitor is in oligovalent or in polyvalent form.

10. The use according to any one of the claims 1-8, wherein the glycoinhibitor is in monovalent form.

11. The use according to any one of claims 1-10 for the treatment of a bacterial infection in gastrointestinal tract.

12. The use according to any one of claims 1-10 for the treatment of oral infection.

13. The use according to the claim 1-10 for the treatment of a bacterial infection in lungs.

14. The use according to claim 7, wherein said oligosaccharide sequence is selected from the following group:

Galβ

4Glc, GalNAcβ

4Galβ

4Glc, Galβ

3GalNAcβ

4Galβ

4Glc, Galβ

3GlcNAcβ

3Galβ

4Glc, Galβ

4GlcNAcβ

3Galβ

4Glc, Galα

4Galβ

4GlcNAc, Galα

4Galβ

Glc, Galβ

3GlcNAc, Galβ

4GlcNAc, Galα

3Galβ

4Glc, Galα

3Galβ

4GlcNAc, GalNAcα

/β

3Galβ

4GlcNAc, GlcNAcβ

3Galβ

4GlcNAc or GlcNAcβ

3Galβ

4Glc

15. The use according to claim 1, wherein the glycoinhibitor is α

-anomeric glycoinhibitor.

16. The use according to claim 1, wherein the glycoinhibitor is NeuNAcα

.

17. The use according to claim 1, wherein the glycoinhibitor is Fucα

.

18. The use according to claim 1, wherein a glycoinhibitor substance comprising a pyranose formed ring structure is selected from a group consisting of GlcNAcβ

, GalNAcβ

, and Galα

.

19. The use according to claim 1, wherein a glycoinhibitor substance comprising a pyranose formed ring structure is selected from a group consisting of GlcNAcβ

and GalNAcβ

.

20. The use according to claim 1, wherein a glycoinhibitor substance comprising a pyranose formed ring structure is selected from a group consisting of GlcNAcβ

, Manα

, and Fucα

.

21. The use according to any one of the preceding claims, wherein at least two different glycoinhibitors are used.

22. The use according to any of the claims 1-21, wherein at least three different glycoinhibitors are used.

23. The use according to claim 1, wherein said disease is caused by the presence of Helicobacter pylori or diarrhea causing E. coli in the gastrointestinal tract of said patient.

24. The use according to claim 1 for the treatment of influenza or coinfection of bacterium and influenza virus, wherein said glycoinhibitor is NeuNAcα

.

26. The use according to claim 1 or 25, wherein the glycoinhibitor is for the treatment of coinfection of bacterium and influenza virus

27. The use according to claim 1 or 25, wherein the coinfection causes pneumonia or bronchitis.

28. The use according to claim 1 or 25, wherein said disease is a secondary bacterial infectious disease associated with influenza and said glycoinhibitor substance is used together with an oligosaccharide substance defined in Formula I of claim 7.

29. The use according to claim 1 or 25, wherein the infecting bacterium is selected from the group consisting of Streptococcus pneumoniae, Escherichia coli, Klebsiella pneumoniae, Pseudomonas auruginosa, Pseudomonas cepacia, Xanthomonas maltophilia, Haemophilus influenzae, Haemophilus parainfluenzae, and Staphylococcus aureus.

31. A composition comprising a substance as defined in claims 1-8, 14-20 and 30 for production of therapheutic or nutritional composition as an additive used for improving quality of a food or feed stuff.

32. Use of a composition comprising a purified fraction(s) of at least two compounds as defined in claims 1-8, 14-20 and 30 for the manufacture of a medicament for prophylaxis or treatment of a gastrointestinal infection.

33. The composition comprising a substance as defined in claims 1-8, 14-20 and 30, wherein said composition is for prophylaxis or treatment of a lung disease.

34. The composition comprising a substance as defined in claims 1-8, 14-20 and 30, wherein said composition is used for the treatment of a human patient.

35. The composition comprising a substance as defined claims 1-8, 14-20 and 30, wherein said composition is used for the treatment of an animal patient.

36. A nutritional composition or a nutritional additive comprising a purified fraction(s) of at least of two substancess as defined in claims 1-8, 14-20 and 30 for prophylaxis or treatment of gastrointestinal infection.

37. A nutritional composition or a nutritional additive according to claim 36 further comprising a probiotic microorganism or a prebiotic substance.

38. Use of a composition comprising a glycoinhibitor as defined in claims 1-8, 14-20 and 30 as a part of filter material to purify pathogens from liquid food, beverages and water by filtering.

39. Use of a composition comprising glycoinhibitors as defined in claims 1-8, 14-20 and 30 in diagnostics.

40. The substance as defined in claims 1-8, 14-20 and 30 for production of therapheutic or nutritional composition is an additive used for improving quality of a food or feed stuff.

41. Infant formula comprising at least two types of glycoinhibitors defined in claims 1-8, 14-20 and 30.

42. A food preservative comprising at least two types of glycoinhibitors defined in claims 1-8, 14-20 and 30.

43. Use of a composition comprising glycoinhibitors defined in claims 1-8, 14-20 and 30 for coating surfaces of food products for improved food safety.

44. A mouth hygiene product comprising at least two types of glycoinhibitors defined in claims 1-8, 14-20 and 30.

45. A mouth hygiene product comprising at least two types of glycoinhibitors defined in claims 1-8, 14-20 and 30.

46. A mouth hygiene product according to the claim 44 or 45 when the product is chosen from group tooth pastes, mouth wash solutions, tablets, and chewing gums.

47. A topical, washing or cosmetic product comprising at least one of the oligosaccharide sequences defined in claims 1-8, 14-20 and 30.

48. A topical, washing or cosmetic product comprising at least two of the oligosaccharide sequences from two different groups defined in claims 1-8, 14-20 and 30.

49. A topical, washing or cosmetic product according to the claim 47 or 48 when the product is chosen from group tooth pastes, mouth wash solutions, tablets, and chewing gums.

50. Use of a composition defined in claims 1-8, 14-20 and 30 for non-diagnostic inhibition or agglutination of pathogen ex vivo.

51. Use according to claim 50 when the pathogen is E. coli.

66. A method of the treatment for a condition, wherein glycosidase enzymes hydrolyze glycoconjugates of a patient to reveal neutral glycan receptors of a pathogenic agent, and wherein the revealed neutral glycan receptor comprise an oligosaccharide sequence according to the following formula

[Galβ

y]_p[Hex(NAc)_rα

/β

z]_sGalβ

4Glc(NAc)_u  

 

(I)

wherein p, r, s, and u are each independently 0 or 1, and y is either linkage position 3 or 4, and z is either linkage position 3 or 4, and Hex is either Gal or Glc, so that when p is 1 and y=3, then Hex is Galβ

or Glcβ and

r=1, or p is 1 and y=4 then Hex is Glcβ and

r=1, when p is 0 and z is 4, then Hex is Galβ and

r is 1 or Hex is Galα and

r is 0, and wherein the pathogenic agent is fungus, virus, toxin, or bacterium, wherein a pharmaceutically effective amount of the glycosidase inhibitor as defined in claim 2 or 11 is administered to a subject in need of such treatment.

25. Use of Oseltamivir, Zanamivir, or RWJ-270201 as glycoinhibitor substance for the manufacture of a medicament for the treatment of a secondary bacterial infectious disease associated with influenza.

30. A substance inhibiting glycosidase enzymes, comprising a glycoinhibitor substance comprising a pyranose formed ring structure selected from the group consisting of:

GlcNAcβ

, GalNAcβ

, Galβ

, Galα

, GalNAcα

, Fucα

, Manα

, and Neu5Acα

.

52. Use of a glycosidase inhibitor for the manufacture of a medicament for the treatment of a disease, wherein glycosidase enzymes hydrolyze glycoconjugates of a patient to reveal neutral glycan receptors of a pathogenic agent, and wherein the revealed neutral glycan receptor comprise an oligosaccharide sequence according to the following formula

[Galβ

y]_p[Hex(NAc)_rα

/β

z]_sGalβ

4Glc(NAc)_u  

 

(I)

wherein p, r, s, and u are each independently 0 or 1, and y is either linkage position 3 or 4, and z is either linkage position 3 or 4, and Hex is either Gal or Glc, so that when p is 1 and y=3, then Hex is Galβ

or Glcβ and

r=l, or p is 1 and y=4 then Hex is Glcβ and

r=1, when p is 0 and z is 4, then Hex is Galβ and

r is 1 or Hex is Galα and

r is 0

and wherein the pathogenic agent is fungus, virus, toxin, or bacterium.

53. Use according to claim 52, wherein said glycosidase inhibitor inhibits one or several glycosidases of the following group:

α

-sialidase, α

-fucosidase, β

-galactosidase, β

-N-acetylhexosaminidase, endo-β

-galactosidase, α

-galactosidase and α

-N-acetylhexosaminidase.

54. Use according to claim 52, wherein said revealed neutral glycan receptor is a part of a glycolipid or glycoprotein

55. Use according to claim 52, wherein said oligosaccharide sequence is selected from the following group:

Galβ

4Glc, GalNAcβ

4Galβ

4Glc, Galβ

3GalNAcβ

4Galβ

4Glc, Galα

4Galβ

4GlcNAc/Glc, Galβ

3GlcNAc, Galβ

4GlcNAc, Galα

3Galβ

4GlcNAc/Glc, GalNAcα

/β

3Galβ

4GlcNAc, or GlcNAcβ

3Galβ

4GlcNAc/Glc,

56. Use according to claim 52, wherein said pathogenic agent is a virus.

57. Use according to claim 56, wherein said virus is a human influenza virus or a rotavirus.

58. Use according to claim 52, wherein said pathogenic agent is a toxin.

59. Use according to claim 58, wherein said toxin is a shiga toxin, a shiga like toxin, heat labile toxin of Escherichia coli or toxin A of Clostridium difficile.

60. Use according to claim 52, wherein said disease is an urinary tract infection, chronic superficial gastritis, gastric ulcer, duodenal ulcer, non-Hodgkin lymphoma in human stomach, gastric adenocarcinoma, heart disease, skin disease, liver disease, pancreatic disease, sudden infant death syndrome or diarrhea caused by Clostridium difficile.

61. Use according to claim 52, wherein said pathogenic agent is a bacterium selected from the group of Streptococcus pneumoniae, Escherichia coli, Klebsiella pneumoniae, Pseudomonas auruginosa, Pseudomonas cepacia, Xanthomonas maltophilia, Haemophilus influenzae, Haemophilus parainfluenzae, Helicobacter pylori and Staphylococcus aureus.

62. Use according to claim 52, wherein said glycosidase inhibitor is Oseltamivir, Zanamivir or RWJ-270201.

63. Use according to claim 52, wherein said disease is a secondary infectious disease associated with influenza.

64. Use according to claim 63, wherein said secondary infectious disease is pneumonia.

65. Use according to claim 52, wherein said disease is caused by the presence of Helicobacter pylori in the gastrointestinal tract of said patient.