Device and method for restoration of the condition of blood
The present invention relates to a device for extracorporeal removal of harmful agents from blood or blood com-Components, comprising full length heparin immobilized on a solid substrate by covalent end point attachment. The present invention also relates to a method for extracorporeal removal of a harmful agent from mammalian blood or blood components. The present invention further relates to a process for covalent end point attachment of full length heparin to a solid substrate.
1. An apparatus for extracorporeal circulation of blood or blood components, comprising a first extracorporeal blood treatment device; and in combination with a second device for removal of harmful agents, which is in combination with the first extracorporeal blood treatment device, wherein said second device comprises heparin immobilized on a solid substrate by covalent end point attachment and is arranged downstream of the first extracorporeal blood treatment device for removal of harmful agents.
2. The apparatus according to claim 1 , wherein said first extracorporeal blood treatment device is an oxygenator or a hemodialysis machine.
3. The apparatus according to claim 1 , wherein said heparin is covalently end point attached full length heparin.
4. The apparatus according to claim 3 , wherein said full length heparin has a mean molecular weight range of 15-25 kDa.
5. The apparatus according to claim 3 , wherein said full length heparin has a mean molecular weight of more than 21 kDa.
6. The apparatus according to claim 3 , wherein the surface concentration of said full length heparin is 1-20 μg/cm 2 .
7. The apparatus according to claim 6 , wherein the surface concentration of said full length heparin is 5-15 μg/cm 2 .
8. The apparatus according to claim 1 , wherein said heparin is covalently attached to said solid substrate via stable secondary amino groups.
9. The apparatus according to claim 1 , wherein the total surface area of said solid substrate is in the range of 0.1-20 m 2 .
10. The apparatus according to claim 9 , wherein the total surface area of said solid substrate is in the range of 0.5-3 m 2 .
11. The apparatus according to claim 9 , wherein said solid substrate comprises particles or beads.
12. The apparatus according to claim 11 , wherein the particle or bead diameter is in the range of 10-1000 μm.
13. The apparatus according to claim 11 , wherein the particle or bead diameter is in the range of 20-200 μm.
14. The apparatus according to claim 11 , wherein said particle or bead comprises a material selected from the group consisting of polyurethanes, polyolefins, silicones, fluoropolymers, poly(methyl methacrylate), glass, cross linked alginates, and cross linked polysaccharides.
15. The apparatus according to claim 1 , wherein said solid substrate comprises one or more hollow fibers.
16. The apparatus according to claim 15 , wherein the inner diameter of said hollow fiber is in the range of 10-1000 μm.
17. The apparatus according to claim 15 , wherein the inner diameter of said hollow fiber is in the range of 20-200 μm.
18. The apparatus according to claim 15 , wherein said hollow fiber comprises a material selected from the group consisting of polysulfones, polyamides, polynitriles, polypropylenes, cross linked alginates, and cellulose.
19. The apparatus according to claim 1 , wherein the second device is a column comprising a casing containing the heparinized solid substrate, said column having an inlet through which blood enters the column and an outlet through which blood exits the column and said inlet and outlet are arranged such that blood entering through the inlet is brought into contact with said heparinized solid substrate before it exits the column through the outlet.
20. A method for hemodialysis, wherein the method comprises: contacting blood from a patient in need thereof with the apparatus according to claim 1 .
21. A method for oxygenation of blood, wherein the method comprises: contacting blood with the apparatus according to claim 1 .
22. A method for the extracorporeal treatment of blood or blood components, wherein the method comprises: contacting blood with the apparatus according to claim 1 .
23. A method for oxygenation of blood, wherein the method comprises: contacting blood from a patient in need thereof with the apparatus according to claim 1 .
24. A method for the treatment of acute sepsis, wherein the method comprises: contacting blood from a patient suspected of suffering from acute sepsis to the apparatus according to claim 1 .
25. The method according to claim 22 , wherein said blood is contacted with said apparatus at a blood flow rate of 2000-7000 mL/min.
26. The method according to claim 20 , wherein said blood is contacted with said apparatus at a blood flow rate of 200-500 mL/min.
27. The method according to claim 23 , wherein said blood is contacted with said apparatus at a blood flow rate of 1-100 mL/min.
28. The apparatus according to claim 14 , wherein the cross-linked polysaccharide is a member selected from the group consisting of agarose, dextran, cellulose, chitosan and starch.
29. The apparatus of claim 1 , wherein the second device is arranged downstream of the first extracorporeal blood treatment device.