Method for Extracorporeal Removal of a Pathogenic Microbe, an Inflammatory Cell or an Inflammatory Protein From Blood

• US 20090136586A1
• Filed: 12/13/2006
• Published: 05/28/2009
• Est. Priority Date: 12/13/2005
• Status: Active Grant

• Current Assignee: ExThera Medical Corporation
• Original Assignee: Exthera AB
• Inventors: Bergstrom, Tomas, Larm, Olle
• Granted Patent: US 9,173,989 B2
• Time in Patent Office: Days
• US Class Current: 424/529
• CPC Class Codes: A61K 31/70 Carbohydrates; Sugars; Derivatives thereof sorbitol A61K31/047
• CPC Class Codes: A61M 1/3679 by absorption A61M1/3675 takes precedence
• CPC Class Codes: A61M 2202/0413 Blood
• CPC Class Codes: A61M 2202/203 Bacteria
• CPC Class Codes: A61M 2202/206 Viruses
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• 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 31/18 for HIV
• CPC Class Codes: A61P 31/20 for DNA viruses
• CPC Class Codes: A61P 31/22 for herpes viruses
• CPC Class Codes: A61P 33/00 Antiparasitic agents
• CPC Class Codes: A61P 33/06 Antimalarials
• CPC Class Codes: A61P 7/08 Plasma substitutes; Perfusion solutions; Dialytics or haemodialytics; Drugs for electrolytic or acid-base disorders, e.g. hypovolemic shock artificial tears A61P27/04
• 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 a method for extracorporeal removal of a pathogenic microbe, an inflammatory cell or an inflammatory protein from mammalian blood/use of a device comprising a carbohydrate immobilized on a solid substrate, said carbohydrate having a binding affinity for a pathogenic microbe, an inflammatory cell or an inflammatory protein, for extracorporeal removal of said pathogenic microbe, inflammatory cell or inflammatory protein from mammalian blood/use of a carbohydrate having a binding affinity for a pathogenic microbe, an inflammatory cell or an inflammatory protein, wherein said carbohydrate is immobilized on a solid substrate, in the preparation of a device for treatment of a condition caused or aggravated by said pathogenic microbe, inflammatory cell or inflammatory protein/and a method for treatment of a mammalian subject suffering from a condition caused or aggravated by a pathogenic microbe, an inflammatory cell or an inflammatory protein.

Claims

1. Method for extracorporeal removal of a pathogenic microbe, an inflammatory cell or an inflammatory protein from mammalian blood, comprising the steps:

a) providing a sample of mammalian blood,

b) bringing said sample into contact with a carbohydrate immobilized on a solid substrate, said carbohydrate having a binding affinity for a pathogenic microbe, inflammatory cell or inflammatory protein, under conditions allowing binding of any pathogenic microbes, inflammatory cells and inflammatory proteins in said blood sample to the carbohydrate,

c) separating the sample from the solid substrate, such that said pathogenic microbe, inflammatory cell or inflammatory protein is at least partially retained on the solid substrate, and

d) recovering said sample containing a reduced amount of said pathogenic microbe, inflammatory cell or inflammatory protein.

2. Method according to claim 1, wherein said pathogenic microbe is selected from the group consisting of bacteria, viruses and parasites.

3. Method according to claim 1, wherein said pathogenic microbe is a virus.

4. Method according to claim 3, wherein said virus is selected from the group consisting of herpes simplex virus type 1, herpes simplex virus type 2, Influenza A virus, cytomegalovirus and human immunodeficiency virus.

5. Method according to claim 4, wherein said virus is selected from the group consisting of herpes simplex virus type 1 and herpes simplex virus type 2.

6. Method according to claim 1, wherein said pathogenic microbe is a bacterium.

7. Method according claim 6, wherein said bacterium is selected from the group consisting of Helicobacter pylori, Streptococcus sanguis, Streptococcus/mutans, Staphylococcus aureus, Escherichia coli, Pseudomonas aureginosa and Mycobacterium tuberculosis.

8. Method according claim 6, wherein said bacterium is Helicobacter pylori or Staphylococcus aureus.

9. Method according to claim 1, wherein said pathogenic microbe is a parasite.

10. Method according to claim 9, wherein said parasite is selected from the group consisting of Plasmodium falciparum and Trypanosoma cruzi.

11. Method according to claim 1, wherein said inflammatory cell is selected from the group consisting of inflammatory lymphocytes and inflammatory macrophages.

12. Method according to claim 1, wherein said inflammatory protein is a pro-inflammatory cytokine.

13. Method according to claim 12, wherein said pro-inflammatory cytokine is selected from the group consisting of tumor necrosis factor alpha (TNF-α

), tumor necrosis factor beta (TNF-β

), interleukin-1 (IL-1), and interleukin-6 (IL-β

).

14. Method according to claim 1, wherein said mammalian blood is human blood.

15. Method according to claim 1, wherein said carbohydrate is selected from the group consisting of heparin, heparan sulfate, chondroitin sulfate, carbohydrates comprising sialic acid and carbohydrates comprising neuramic acid.

16. Method according to claim 15, wherein said carbohydrate is heparin.

17. Method according to claim 1, wherein said solid substrate comprises microparticles.

18. Method according to claim 1, wherein said solid substrate comprises one or more hollow fibres.

19. Method according to claim 1, wherein the material of said solid substrate is selected from the group consisting of glass, cellulose, cellulose acetate, chitin, chitosan, crosslinked dextran, crosslinked agarose, polypropylene, polyethylene, polysulfone, polyacrylonitrile, silicone, Teflon and polyurethanes.

20. Method according to claim 1, wherein said carbohydrate is covalently linked to said solid substrate.

21. Method according to claim 1, wherein said carbohydrate is linked to said solid substrate by covalent end-point attachment.

22-41. -41. (canceled)

42. Method for treatment of a mammalian subject suffering from a condition caused or aggravated by a pathogenic microbe, an inflammatory cell or an inflammatory protein, comprising the steps:

a) extracting blood from the subject,

b) bringing the extracted blood into contact with a device comprising a carbohydrate immobilized on a solid substrate, said carbohydrate having a binding affinity for a pathogenic microbe, an inflammatory cell or an inflammatory protein, under conditions allowing binding of a pathogenic microbe, an inflammatory cell or an inflammatory protein to the carbohydrate, and

c) reintroducing the blood, containing a reduced amount of said pathogenic microbe, inflammatory cell or inflammatory protein, into the bloodstream of the subject.

43. Method according to claim 42, wherein the extraction and reintroduction of blood is performed in a continuous loop, which loop comprises a part of the bloodstream of the subject.

44. Method according to claim 42, wherein said pathogenic microbe is selected from the group consisting of bacteria, viruses and parasites.

45. Method according to claim 44, wherein said pathogenic microbe is a virus.

46. Method according to claim 45, wherein said virus is selected from the group consisting of herpes simplex virus type 1, herpes simplex virus type 2, Influenza A virus, cytomegalovirus and human immunodeficiency virus.

47. Method according to claim 46, wherein said virus is selected from the group consisting of herpes simplex virus type 1 and herpes simplex virus type 2.

48. Method according to claim 44, wherein said pathogenic microbe is a bacterium.

49. Method according claim 48, wherein said bacterium is selected from the group consisting of Helicobacter pylori, Streptococcus sanguis, Streptococcus mutans, Staphylococcus aureus, Escherichia coli, Pseudomonas aureginosa and Mycobacterium tuberculosis.

50. Method according claim 49, wherein said bacterium is Helicobacter pylori or Staphylococcus aureus.

51. Method according to claim 44, wherein said pathogenic microbe is a parasite.

52. Method according to claim 51, wherein said parasite is selected from the group consisting of Plasmodium falciparum and Trypanosoma cruzi.

53. Method according to claim 42, wherein said inflammatory cell is selected from the group consisting of inflammatory lymphocytes and inflammatory macrophages.

54. Method according to claim 42, wherein said inflammatory protein is a pro-inflammatory cytokine.

55. Method according to claim 54, wherein said pro-inflammatory cytokine is selected from the group consisting of tumor necrosis factor alpha (TNF-α

), tumor necrosis factor beta (TNF-β

), interleukin-1 (IL-1), and interleukin-6 (IL-6).

56. Method according to claim 42, wherein said carbohydrate is selected from the group consisting of heparin, heparan sulfate, chondroitin sulfate, and carbohydrates comprising sialic acid and carbohydrates comprising neuramic acid.

57. Method according to claim 56, wherein said carbohydrate is heparin.

58. Method according to claim 42, wherein said solid substrate comprises microparticles.

59. Method according to claim 42, wherein said solid substrate comprises one or more hollow fibres.

60. Method according to claim 42, wherein said solid substrate is selected from the group consisting of glass, cellulose, cellulose acetate, chitin, chitosan, crosslinked dextran, crosslinked agarose, polypropylene, polyethylene, polysulfone, polyacrylonitrile, silicone, Teflon and polyurethanes.