Multi-functional hemocompatible porous polymer bead sorbent for removing protein based toxins and potassium from biological fluids
Inventors
Golobish, Thomas • Gruda, Maryann • Guliashvili, Tamaz • O'SULLIVAN, Pamela • SCHEIRER, Andrew • DAN, Vi • Young, Wei-Tai • Capponi, Vincent • Chan, Phillip
Assignees
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Publication Number
US-11040061-B2
Publication Date
2021-06-22
Expiration Date
Abstract
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.
Core Innovation
The invention relates to a biocompatible polymer system comprising at least one polymer that includes a plurality of pores and a sulfonic acid salt functionality. The polymer system is capable of adsorbing protein based toxins, inflammatory mediators, and positively charged ions, and the polymer further includes residues of one or more monomers selected from acrylonitrile, butyl acrylate, butyl methacrylate, cetyl acrylate, cetyl methacrylate, divinylbenzene, ethyl acrylate, ethyl methacrylate, ethylstyrene, methyl acrylate, methyl methacrylate, octyl acrylate, octyl methacrylate, styrene, vinylbenzyl alcohol, vinylformamide, vinylnaphthalene, and vinyltoluene.
The pore structure is defined by a total volume of pore sizes in the range of from 10 1 to 40,000 1 greater than 0.1 cc/g and less than 5.0 cc/g dry polymer. The biocompatible polymer system has improved biocompatibility using a coating selected from poly(hydroxyethyl methacrylate), poly(hydroxyethyl acrylate), poly(dimethylaminoethyl methacrylate), salts of poly(acrylic acid), salts of poly(methacrylic acid), poly(diethylaminoethyl methacrylate), poly(hydroxypropyl methacrylate), poly(hydroxypropyl acrylate), poly(N-vinylpyrrolidone), poly(vinyl alcohol), heparin-mimicking polymers, mixtures thereof, or a coating comprising heparin.
In the polymer’s sulfonated form, the polymer is in the form of a crosslinked polymer or a porous polymer, and sulfonation occurs under mild conditions that retain residual functionality of unreacted double bonds and chloromethyl groups. A related embodiment specifies a macroreticular porous polymer that is sulfonated under mild conditions while retaining residual functionality of any unreacted double bonds.
Claims Coverage
The partial set includes two independent claims. Across these claims, the inventive features are a porous sulfonic acid salt polymer for adsorption of protein based toxins, inflammatory mediators, and positively charged ions; a quantitative pore-volume range; specified coatings for improved biocompatibility; and mild sulfonation that retains residual double-bond/chloromethyl functionality, with the polymer form limited to crosslinked/porous or macroreticular porous polymer in the respective independent claim.
Porous sulfonic acid salt polymer for adsorption of protein based toxins and positively charged ions
A biocompatible polymer system comprising at least one polymer having a plurality of pores and a sulfonic acid salt functionality; the polymer system is capable of adsorbing protein based toxins, inflammatory mediators, and positively charged ions.
Selected sulfonatable monomer residues in the polymer
The polymer comprises residues of one or more monomers selected from acrylonitrile, butyl acrylate, butyl methacrylate, cetyl acrylate, cetyl methacrylate, divinylbenzene, ethyl acrylate, ethyl methacrylate, ethylstyrene, methyl acrylate, methyl methacrylate, octyl acrylate, octyl methacrylate, styrene, vinylbenzyl alcohol, vinylformamide, vinylnaphthalene, and vinyltoluene.
Pore structure total volume constraint
The polymer's pore structure has a total volume of pore sizes in the range of from 10 1 to 40,000 1 greater than 0.1 cc/g and less than 5.0 cc/g dry polymer.
Improved biocompatibility by specified coatings including heparin or heparin-mimicking polymers
The biocompatible polymer system has improved biocompatibility by use of a coating selected from poly(hydroxyethyl methacrylate), poly(hydroxyethyl acrylate), poly(dimethylaminoethyl methacrylate), salts of poly(acrylic acid), salts of poly(methacrylic acid), poly(diethylaminoethyl methacrylate), poly(hydroxypropyl methacrylate), poly(hydroxypropyl acrylate), poly(N-vinylpyrrolidone), poly(vinyl alcohol), heparin-mimicking polymers, mixtures thereof, or a coating comprising heparin.
Mild sulfonation retaining residual functionality in crosslinked or porous polymer
The polymer is in the form of a crosslinked polymer or a porous polymer; the crosslinked polymer or porous polymer has been sulfonated under mild conditions that retain residual functionality of any unreacted double bonds and chloromethyl groups.
Macroreticular porous polymer with mild sulfonation retaining unreacted double bonds
The polymer is in the form of a macroreticular porous polymer that has been sulfonated under mild conditions that retain residual functionality of any unreacted double bonds.
Overall, the independent claims require a biocompatible porous polymer with sulfonic acid salt functionality and defined pore-volume ranges, configured to adsorb protein based toxins and inflammatory mediators while removing positively charged ions. Biocompatibility is improved by specified coatings, including heparin or heparin-mimicking polymers, and sulfonation is performed under mild conditions that retain residual double-bond functionality and chloromethyl groups in the crosslinked/porous embodiment.
Stated Advantages
Improved biocompatibility by use of specified coatings including heparin or heparin-mimicking polymers.
Documented Applications
Not explicitly described in patent.
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