Use Of A Hemocompatible Porous Polymer Bead Sorbent For Removal Of Endotoxemia-Inducing Molecules
The invention concerns biocompatible polymer systems comprising at least one polymer with a plurality of pores, said polymer comprising either polyol or zwitterionic groups designed to adsorb endotoxins and other inflammatory mediator molecules.
1 . A biocompatible polymer system comprising at least one polymer, said polymer comprising either polyol or zwitterionic functionality; said polymer system capable of adsorbing endotoxins.
2 . The biocompatible polymer system of claim 1 wherein the polymer system is also capable of adsorbing a broad range of toxins and inflammatory mediators.
3 . The biocompatible polymer system of claim 2 wherein the said toxins and inflammatory mediators have a molecular weight of from less than about 0.5 kDa to about 1,000 kDa.
4 . The biocompatible polymer system of claim 2 wherein the said toxins and inflammatory mediators have a molecular weight of from less than about 0.5 kDa to about 60 kDa.
5 . The biocompatible polymer system of claim 2 wherein the toxins and inflammatory mediators comprise one or more of cytokines, pathogen-associated molecular pattern molecules (PAMPs), damage-associated molecular pattern molecules (DAMPs), superantigens, monokines, chemokines, interferons, proteases, enzymes, peptides including bradykinin, soluble CD40 ligand, bioactive lipids, oxidized lipids, cell-free hemoglobin, cell-free myoglobin, growth factors, glycoproteins, prions, toxins, bacterial and viral toxins, drugs, vasoactive substances, foreign antigens, and antibodies.
6 . The biocompatible polymer system of claim 1 wherein the polymer system is also capable of adsorbing one or more of gram-negative bacteria, gram-negative bacteria fragments, and gram-negative bacterial components, such as lipopolysaccharide (LPS).
7 . The biocompatible polymer system of claim 1 wherein the polymer system is also capable of adsorbing one or more of gram-positive bacteria, gram-positive bacteria fragments, and gram-positive bacterial components, such as lipoteichoic acid (LTA).
8 . The biocompatible polymer system of claim 1 wherein said polymer is made using suspension polymerization, emulsion polymerization, bulk polymerization, or precipitation polymerization.
9 . The biocompatible polymer system of claim 1 wherein the polymer is made by modification of a cellulosic polymer, wherein said modifications optionally include the addition of lipophilic substrates that comprise aryl or alkyl groups, along with polyol or zwitterionic substrates, added via free-radical or S N 2 type chemistries.
10 . The biocompatible polymer system of claim 1 wherein the polymer system has the form of a solid support, which may include but is not limited to a bead, fiber, monolithic column, film, membrane, or semi-permeable membrane.
11 . The biocompatible polymer system of claim 10 wherein the solid support has a biocompatible hydrogel coating.
12 . The biocompatible polymer system of claim 1 wherein the polymer comprises a plurality of pores and the polymer's pore structure has a total volume of pore sizes in the range of from 10 Å to 40,000 Å greater than 0.1 cc/g and less than 5.0 cc/g dry polymer.
13 . The biocompatible polymer system of claim 1 wherein the polymer is nonporous.
14 . The biocompatible polymer system of claim 1 wherein said polymer is a hypercrosslinked polymer.
15 . The biocompatible polymer system of claim 1 wherein the polymer is hemocompatible.
16 . The biocompatible polymer system of claim 1 wherein the agent used to imbue biocompatibility is either (i) heparin or (ii) a heparin mimicking polymer.
17 . The biocompatible polymer system of claim 1 wherein the polymer is formed and subsequently modified to be biocompatible.
18 . The biocompatibility imbuing modification of claim 17 wherein the agent used to imbue biocompatibility is either (i) heparin or (ii) a heparin mimicking polymer.
19 . A device for removing endotoxins from physiologic fluid comprising the biocompatible polymer system of any one of claims 1 - 18 .
20 . The device of claim 19 wherein said device also removes a broad range of toxins and inflammatory mediators.
21 . The device of claim 20 wherein the said toxins and inflammatory mediators have a molecular weight of from less than about 0.5 kDa to about 1,000 kDa.
22 . The device of claim 20 wherein the said toxins and inflammatory mediators have a molecular weight of from less than about 0.5 kDa to about 60 kDa.
23 . The device of claim 20 wherein the toxins and inflammatory mediators comprise one or more of cytokines, pathogen-associated molecular pattern molecules (PAMPs), damage-associated molecular pattern molecules (DAMPs), superantigens, monokines, chemokines, interferons, proteases, enzymes, peptides including bradykinin, soluble CD40 ligand, bioactive lipids, oxidized lipids, cell-free hemoglobin, cell-free myoglobin, growth factors, glycoproteins, prions, toxins, bacterial and viral toxins, drugs, vasoactive substances, foreign antigens, and antibodies.
24 . The device of claim 19 wherein said device also removes one or more of gram-negative bacteria, gram-negative bacteria fragments, and gram-negative bacterial components, such as lipopolysaccharide (LPS).
25 . The device of claim 19 wherein said device also removes one or more of gram-positive bacteria, gram-positive bacteria fragments, and gram-positive bacterial components, such as lipoteichoic acid (LTA).
26 . A device for removing endotoxins from non-physiologic fluid comprising the biocompatible polymer system of any one of claims 1 - 18 .
27 . The device of claim 26 wherein said device also removes a broad range of toxins and inflammatory mediators.
28 . The device of claim 27 wherein the said toxins and inflammatory mediators have a molecular weight of from less than about 0.5 kDa to about 1,000 kDa.
29 . The device of claim 27 wherein the said toxins and inflammatory mediators have a molecular weight of from less than about 0.5 kDa to about 60 kDa.
30 . The device of claim 27 wherein the toxins and inflammatory mediators comprise one or more of cytokines, pathogen-associated molecular pattern molecules (PAMPs), damage-associated molecular pattern molecules (DAMPs), superantigens, monokines, chemokines, interferons, proteases, enzymes, peptides including bradykinin, soluble CD40 ligand, bioactive lipids, oxidized lipids, cell-free hemoglobin, cell-free myoglobin, growth factors, glycoproteins, prions, toxins, bacterial and viral toxins, drugs, vasoactive substances, foreign antigens, and antibodies.
31 . The device of claim 26 wherein said device also removes one or more of gram-negative bacteria, gram-negative bacteria fragments, and gram-negative bacterial components, such as lipopolysaccharide (LPS).
32 . The device of claim 26 wherein said device also removes one or more of gram-positive bacteria, gram-positive bacteria fragments, and gram-positive bacterial components, such as lipoteichoic acid (LTA).
33 . The biocompatible polymer system of any one of claims 1 - 18 is in a device suitable to retain the polymer and be incorporated into an extracorporeal circuit.
34 . A method of perfusion comprising passing a physiologic fluid once through or multiple times by way of a suitable extracorporeal circuit through a device comprising the biocompatible polymer system of any one of claims 1 - 18 .
35 . The biocompatible polymer system of any one of claims 1 - 18 is housed in a container suitable to retain the polymer and for transfusion of blood products, including whole blood, packed red blood cells, platelets, albumin, plasma or any combination thereof.
36 . The biocompatible polymer system of any one of claims 1 - 18 that removes endotoxin from blood products, including whole blood, plasma, or serum, or from other physiologic fluids.
37 . The biocompatible polymer system of any one of claims 1 - 18 wherein the polymer is enterally or rectally administered.
38 . A polymer system comprising at least one polymer, said polymer comprising either polyol or zwitterionic functionality; said polymer system capable of adsorbing endotoxins.
39 . The polymer system of claim 38 wherein the polymer system is also capable of adsorbing one or more of a broad range of toxins, gram-negative bacteria, gram-negative bacteria fragments, gram-negative bacterial components, such as lipopolysaccharide (LPS), gram-positive bacteria, gram-positive bacteria fragments, and gram-positive bacterial components, such as lipoteichoic acid (LTA).
40 . The polymer system of claim 39 wherein the said toxins have a molecular weight of from less than about 0.5 kDa to about 1,000 kDa.