Use of a hemocompatible porous polymer bead sorbent for removal of endotoxemia-inducing molecules
Inventors
Guliashvili, Tamaz • Golobish, Thomas • Gruda, Maryann • O'SULLIVAN, Pamela • SCHEIRER, Andrew • Capponi, Vincent • Chan, Phillip • Young, Wei-Tai
Assignees
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Publication Number
US-11065600-B2
Publication Date
2021-07-20
Expiration Date
Abstract
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. The inventions are in the field of porous polymeric sorbents, also in the field of broadly reducing endotoxins in blood and blood products that can cause endotoxemia, additionally, in the field of broadly removing endotoxins by perfusion or hemoperfusion.
Core Innovation
The invention relates to hemocompatible porous polymer sorbent systems for adsorbing endotoxins (lipopolysaccharides) and inflammatory mediators in blood or other physiologic fluids. The sorbent includes a solid support bearing a polymer coating with polyol or zwitterionic functionality, and the polymer coating is covalently bound to a porous polymer backbone, including poly(styrene-co-divinylbenzene) beads, with hypercrosslinked or nonporous variants.
The described polymer systems are used by contacting the physiologic fluid with the polymer system, including in perfusion and hemoperfusion configurations using packed bead beds. The document evaluates thrombogenicity and provides pore-structure rationale with quantitative pore-volume distributions, using micropores, mesopores, and macropores, including transport pores, capacity pores, and effective pores, along with cumulative pore metrics.
Material examples describe functionalization that includes diol groups and zwitterion incorporation, with the zwitterionic functionality described as sulfobetaine. The examples report characterization including measured pore volume and cumulative pore metrics and XPS atomic composition, and they report dynamic recirculation model results for endotoxin and cytokine removal. Example protein targets and broad classes of adsorbable toxins and inflammatory proteins are listed along with molecular-weight ranges.
Claims Coverage
The independent claim covers a method of adsorbing endotoxins by contacting physiologic fluid with a solid support polymer system having either polyol or zwitterionic functionality, where the polymer coating is selected from a specified list of poly(vinyl) and poly(acrylate/methacrylate) polymers and salts. The claim set adds five inventive features in dependent claims, covering nonporous polymer, heparin or heparin-mimicking polymer, molecular weight constraints, and repeated extracorporeal circuit passing through a device containing the polymer system.
Contacting physiologic fluid with a polymer system having polyol or zwitterionic functionality
Contacting physiologic fluid with a polymer system comprising either polyol or zwitterionic functionality to adsorb endotoxins, where the polymer system has the form of a solid support having a polymer coating with selected polymer compositions.
Polymer coating selected from specified poly(vinyl) and poly(acrylate/methacrylate) polymers and salts
Using a polymer coating comprising poly(diethylaminoethyl methacrylate), poly(dimethylaminoethyl methacrylate), poly(hydroxyethyl acrylate), poly(hydroxyethyl methacrylate), poly(hydroxypropyl acrylate), poly(hydroxypropyl methacrylate), poly(N-vinylpyrrolidone), poly(vinyl alcohol), salts of poly(acrylic acid), salts of poly(methacrylic) acid, or mixtures thereof.
Nonporous polymer system
Employing the polymer system as a nonporous polymer system.
Heparin or heparin-mimicking polymer as part of the polymer system
Including a polymer system comprising either heparin or a heparin-mimicking polymer.
Molecular weight constrained adsorption targets
Adsorbing toxins and inflammatory mediators having a molecular weight ranging from less than 0.5 kDa to 1,000 kDa.
Repeated extracorporeal circuit passing through a polymer-containing device
Passing the physiologic fluid one or more times through an extracorporeal circuit comprising a device with the polymer system.
Overall, the claim coverage centers on adsorbing endotoxins by contacting physiologic fluid with a solid-support polymer coating exhibiting polyol or zwitterionic functionality, using a defined set of poly(acrylate/methacrylate) and vinyl polymers or their salts. Dependent features further specify nonporous polymer, heparin or heparin-mimicking polymer inclusion, molecular-weight constraints for toxins and inflammatory mediators, and an extracorporeal circuit configuration with one or more passes through a device containing the polymer system.
Stated Advantages
Adsorbs endotoxins by contacting physiologic fluid with the described polymer system.
Provides removal of endotoxin and cytokines as reported by dynamic recirculation model results.
Evaluates thrombogenicity of the polymer system using unactivated partial thromboplastin time (uPTT) and provides associated results for minimal activator behavior in examples.
Documented Applications
Perfusion/hemoperfusion via packed bead beds using the polymer sorbent system for contacting blood or physiologic fluids to remove endotoxin and inflammatory mediators, with dynamic recirculation model reporting endotoxin and cytokine removal.
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