Multi-functional hemocompatible porous bead sorbent for removing protein based toxins and potassium from biological fluids
The invention concerns biocompatible polymer systems comprising at least one polymer with a plurality of pores, said polymer comprising a sulfonic acid salt functionality designed to adsorb a broad range of protein based toxins from less than 0.5 kDa to 1,000 kDa and positively charged ions including but not limited to potassium.
1. A method of removing 1) at least one of protein based toxins and inflammatory mediators; and 2) positively charged ions, the method comprising
contacting a physiological fluid with a biocompatible polymer system comprising at least one polymer, the at least one polymer comprising (i) a plurality of pores and (ii) a sulfonic acid salt functionality;
wherein the at least one polymer is in the form of hypercrosslinked or a macroreticular porous polymer that has been sulfonated under mild conditions that retain residual functionality of any unreacted double bonds and chloromethyl groups.
2. The method of claim 1 , wherein the said toxins and inflammatory mediators have a molecular weight of from about 0.5 kDa to about 1,000 kDa.
3. The method of claim 1 , wherein the said toxins and inflammatory mediators have a molecular weight of from about 1 kDa to about 1,000 kDa.
4. The method of claim 1 , wherein the at least one polymer's pore structure has a total volume of pore sizes in the range of from 10 A to 40,000 A greater than 0.1 cc/g and less than 5.0 cc/g dry polymer.
5. The method of claim 1 , wherein the at least one polymer is hemocompatible.
6. The method of claim 1 , wherein an agent is used to imbue biocompatibility that is either (i) heparin or (ii) a heparin mimicking polymer.
7. The method of claim 1 , wherein the at least one polymer is formed and subsequently made to be biocompatible.
8. The method of claim 7 , wherein an agent used to imbue biocompatibility is either (i) heparin or (ii) a heparin mimicking polymer.
9. The method of claim 1 , wherein the polymer system has the form of a solid support.
10. The method of claim 9 , wherein the solid support is a bead, fiber, monolithic column, film, membrane, or semi-permeable membrane.
11. The method of claim 1 , wherein the toxins and inflammatory mediators comprise of one or more of cytokines, superantigens, monokines, chemokines, interferons, proteases, enzymes, peptides including bradykinin, soluble CD40 ligand, bioactive lipids, oxidized lipids, cell-free hemoglobin, cell-free myoglobin, DAMPS, growth factors, glycoproteins, prions, toxins, bacterial and viral toxins, PAMPS, endotoxins, drugs, vasoactive substances, foreign antigens, antibodies, and positively charged ions.
12. The method of claim 9 , wherein the solid support has a biocompatible hydrogel coating.
13. The method of claim 1 , wherein the positively charged ion is potassium.
14. The method of claim 1 , wherein the at least one polymer is made using suspension polymerization, emulsion polymerization, bulk polymerization, or precipitation polymerization.
15. The method of claim 1 , wherein the at least one polymer is a hypercrosslinked polymer.
16. The method of claim 1 , wherein the unreacted double bonds or chloromethyl groups can be modified via free radical or SN type chemistry to attach one or more of biocompatible and hemocompatible monomers, cross-linkers or low molecular weight oligomers.
17. The method of claim 1 , wherein the at least one polymer comprises sulfonic acid groups or a salt thereof, sulfonyl chloride, or sulfonate ester groups.
18. The method of claim 17 , wherein the at least one polymer comprising sulfonic acid groups or a salt thereof, sulfonyl chloride, or sulfonate ester groups is produced by graft copolymerization of (i) premade porous polymer that contains unreacted double bonds with (ii) polymerizable vinyl monomers containing sulfonic acid groups or a salt thereof to form a mixture comprising hemocompatible vinyl monomers.
19. The method of claim 1 , wherein the biocompatible polymer system is constructed from polymerizable vinyl monomers containing sulfonic acid groups or a salt thereof which are copolymerized in the presence of cross-linker, hemocompatible monomer, monomer and suitable porogen to yield porous polymeric polymer containing a sulfonic acid salt functionality.
20. The method of claim 1 , wherein the at least one polymer is housed in a container suitable to retain the polymer and for transfusion of whole blood, packed red blood cells, platelets, albumin, plasma or any combination thereof.
21. The method of claim 1 , wherein the at least one polymer is in a device suitable to retain the polymer and be incorporated into an extracorporeal circuit.