Method for removing cytokines from blood with surface immobilized polysaccharides
First Claim
1. A device for removing at least one adsorbate selected from cytokines, pathogens and toxins from blood which comprises a container, said container comprising a solid substrate of high surface area having at least one polysaccharide adsorbent on the surface thereof with a binding affinity for the adsorbate, wherein said substrate is sufficiently solid such that the adsorbate does not pass through pores in said substrate, and wherein the size of interstitial channel spaces within said substrate is large enough to permit the transport of blood cells, and the amount of interstitial surface area within said substrate is such that when flowing blood is in contact with said substrate through said device, said cytokine, pathogen or toxin binds to binding sites on said at least one polysaccharide adsorbent, becoming separated from said blood and the transport of said adsorbates from blood to adsorbent sites on said substrate is primarily by convection transport, such that adsorbate binding does not require the Brownian diffusion of adsorbates into pores within said substrate.
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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 micro-porous 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.
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Citations
31 Claims
- 1. A device for removing at least one adsorbate selected from cytokines, pathogens and toxins from blood which comprises a container, said container comprising a solid substrate of high surface area having at least one polysaccharide adsorbent on the surface thereof with a binding affinity for the adsorbate, wherein said substrate is sufficiently solid such that the adsorbate does not pass through pores in said substrate, and wherein the size of interstitial channel spaces within said substrate is large enough to permit the transport of blood cells, and the amount of interstitial surface area within said substrate is such that when flowing blood is in contact with said substrate through said device, said cytokine, pathogen or toxin binds to binding sites on said at least one polysaccharide adsorbent, becoming separated from said blood and the transport of said adsorbates from blood to adsorbent sites on said substrate is primarily by convection transport, such that adsorbate binding does not require the Brownian diffusion of adsorbates into pores within said substrate.
- 14. A device for removing at least one adsorbate selected from cytokines, pathogens and toxins from blood which comprises a container that comprises a solid substrate comprised of a plurality of rigid polyethylene beads comprising heparin on the surface thereof with a binding affinity for the adsorbate, wherein said beads are sufficiently solid such that the adsorbate does not pass through pores in said beads, and wherein the size of interstitial channel spaces within said substrate is large enough to permit the transport of blood cells, and the amount of interstitial surface area within said substrate is such that when flowing blood is in contact with said substrate through said device, said cytokine, pathogen or toxin binds to binding sites on said heparin, becoming separated from said blood and the transport of said adsorbates from blood to adsorbent sites on said beads is primarily by convection transport, such that adsorbate binding does not require the Brownian diffusion of adsorbates into pores within said substrate and wherein said heparin is attached to the substrate by covalent end-point attachment in an amount of 0.5-10 mg heparin per gram of bead.
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23. A device for removing at least one adsorbate selected from cytokines, pathogens and toxins from blood which comprises a container, said container comprising a solid substrate of high surface area comprising:
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i) a first portion of the solid substrate with at least one polysaccharide adsorbent on the surface, wherein said at least one polysaccharide comprises binding sites for the at least one adsorbate; and ii) a second portion of the solid substrate having on the surface thereof a cationic, positively charged molecule being more thrombogenic than heparin, wherein said substrate is sufficiently solid such that the adsorbate does not pass through pores in said substrate, and wherein the size of interstitial channel spaces within said substrate is large enough to permit the transport of blood cells, and the amount of interstitial surface area within said substrate is such that when flowing blood is in contact with said substrate through said device, said cytokine, pathogen and toxin becoming separated from said blood and the transport of said adsorbates from blood to adsorbent sites on said substrate is primarily by convection transport, such that adsorbate binding does not require the Brownian diffusion of adsorbates into pores within said substrate. - View Dependent Claims (24, 25, 26, 27, 28, 29, 30, 31)
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Specification