Methods for removing cytokines from blood with surface immobilized polysaccharides

• US 10,086,126 B2
• Filed: 06/30/2016
• Issued: 10/02/2018
• Est. Priority Date: 12/01/2009
• Status: Active Grant

• Current Assignee: ExThera Medical Corporation
• Original Assignee: ExThera Medical Corporation
• Inventors: Ward, Robert S, McCrea, Keith R, Larm, Olle, Adolfsson, Lars
• Primary Examiner(s): Marcetich, Adam
• Application Number:
  US15/199,737
• Publication Number:
  US 20160331886A1
• Time in Patent Office: 824 Days
• CPC Class Codes: A61K 31/60 Salicylic acid; Derivatives thereof
• CPC Class Codes: A61K 31/722 Chitin, chitosan
• CPC Class Codes: A61K 31/727 Heparin; Heparan
• CPC Class Codes: A61K 31/728 Hyaluronic acid
• CPC Class Codes: A61M 1/3472 with treatment of the filtrate
• CPC Class Codes: A61M 1/3486 Biological, chemical treatment, e.g. chemical precipitation; treatment by absorbents
• CPC Class Codes: A61M 1/3496 Plasmapheresis; Leucopheresis; Lymphopheresis A61M1/3472 takes precedence
• CPC Class Codes: A61M 1/36 Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits
• CPC Class Codes: A61M 1/362 changing physical properties of target cells by binding them to added particles to facilitate their subsequent separation from other cells, e.g. immunoaffinity
• CPC Class Codes: A61M 1/3621 Extra-corporeal blood circuits single-needle circuits A61M1/30
• CPC Class Codes: A61M 1/3673 Anticoagulant coating, e.g. Heparin coating
• CPC Class Codes: A61M 1/3679 by absorption A61M1/3675 takes precedence
• CPC Class Codes: A61M 1/3687 Chemical treatment A61M1/3675 takes precedence
• CPC Class Codes: A61M 1/38 Removing constituents from donor blood and storing or returning remainder to body , e.g. for transfusion
• CPC Class Codes: A61M 2202/0057 retained by adsorption
• 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 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection

Abstract

The present invention is directed to a method for removing cytokines and/or pathogens from blood or blood serum (blood) by contacting the blood with a solid, essentially non microporous substrate which has been surface treated with heparin, heparan sulfate and/or other molecules or chemical groups (the adsorbent media or media) having a binding affinity for the cytokine or pathogen(s) to be removed (the adsorbates), and wherein the size of the interstitial channels within said media is balanced with the amount of media surface area and the surface concentration of binding sites on the media in order to provide adequate adsorptive capacity while also allowing relatively high flow rates of blood through the adsorbent media.

Claims

1. A cartridge for extracorporeal removal of at least one adsorbate, the cartridge comprising:

a first media being a heparinized media; and

a second media, which is cationic and more thrombogenic than the first media.

2. The cartridge of claim 1, wherein the first media and the second media are arranged in a layered approach.

3. The cartridge of claim 1, wherein the first media and the second media are blended.

4. The cartridge of claim 3, wherein the blend is random.

5. The cartridge of claim 1, wherein the first media and the second media are arranged in a parfait fashion.

6. The cartridge of claim 1, wherein the first media are beads comprising a polymer of polyethylene.

7. The cartridge of claim 6, wherein the beads have a diameter ranging from 100 and 450 microns.

8. The cartridge of claim 7, wherein the beads have an average diameter of 300 microns.

9. The cartridge of claim 1, wherein the beads are coated with 0.5 mg to 10 mg heparin per gram of bead.

10. The cartridge of claim 9, wherein the heparin is attached to the bead by covalent end-point attachment.

11. The cartridge of claim 1, wherein the second media are beads.

12. The cartridge of claim 11, wherein the beads are coated with a member selected from the group consisting of PEI, chitosan or sialic acid.

13. The cartridge of claim 1, wherein the first media and the second media are present in a ratio of 1:

1.

14. The cartridge of claim 1, wherein the first media and the second media are present in a ratio of 2:

1.

15. The cartridge of claim 1, wherein the cartridge comprises a third media.

16. The cartridge of claim 15, wherein the third media is mannose functionalized beads.

17. The cartridge of claim 1, wherein the cartridge is adapted to be used in series with extracorporeal circuits.

18. A cartridge adapted for extracorporeal blood circuit, the cartridge comprising:

a first media being a heparinized media; and

a second media, which is cationic and more thrombogenic than the first media.