Hemocompatibility modifiers for cross-linked polymeric material
Inventors
Golobish, Thomas D. • Capponi, Vincent J. • Clay, David R.
Assignees
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Publication Number
US-11020521-B2
Publication Date
2021-06-01
Expiration Date
Abstract
The invention concerns methods of removing undesirable molecules from the blood or physiologic fluid; said method comprising contacting said blood or physiologic fluid with a sorbent, said sorbent comprising a plurality of solid forms and comprising a cross-linked polymeric material having a plurality of ligands attached to the surface of said cross-linked polymeric material, comprising (i) zwitterionic moieties, (ii) oligo(ethylene glycol) moieties or (iii) mixtures thereof; said contacting comprising said sorbent sorbing a plurality of said undesirable molecules when said sorbent is administered within a patient's body.
Core Innovation
The invention provides a method of removing undesirable molecules from a physiologic fluid by contacting the physiologic fluid with a sorbent. The sorbent comprises a cross-linked polymeric material in a plurality of solid forms, with a plurality of ligands attached to the surface of the cross-linked polymeric material, and the ligands comprise zwitterionic moieties, including carboxybetaine and sulfobetaine zwitterionic moieties.
The sorbent is administered orally or rectally. The sorbent comprises particles having a diameter in the range from 0.1 micrometers to 2 centimeters, and the particles are characterized by a pore structure with a total volume of pore sizes in the range of from 10 Å to 10,000 Å, with total volume between greater than 0.5 cc/g dry polymer and 3.0 cc/g dry polymer.
The cross-linked polymeric material is derived from the reaction of a cross-linker with one or more polymerizable monomers including divinyl-benzene and styrene, and other listed polymerizable monomers. The undesirable molecules include biologically active molecules, biological response modifiers, products of hemolysis, products of membrane or cellular degradation, toxins, drugs, antibodies, and prions, including undesirable molecules found in stored blood and blood products.
Claims Coverage
The consolidated set identifies one independent claim, covering removal of undesirable molecules from a physiologic fluid by contacting the fluid with a sorbent having surface-attached zwitterionic ligands, specified particle and pore structure features, a cross-linked polymer composition, and oral or rectal administration. The independent claim contains four inventive feature groups.
Surface-attached zwitterionic ligands on a cross-linked polymer sorbent
A sorbent comprising solid forms of a cross-linked polymeric material having a plurality of ligands attached to the surface of the cross-linked polymeric material, where the ligands comprise zwitterionic moieties, including carboxybetaine and sulfobetaine zwitterionic moieties.
Oral or rectal administration of the sorbent
The sorbent is administered orally or rectally.
Particle size and pore-structure total volume constraints
The sorbent comprises particles having a diameter in the range from 0.1 micrometers to 2 centimeters, with a pore structure having a total volume of pore sizes in the range of from 10 Å to 10,000 Å and a total volume between greater than 0.5 cc/g dry polymer and 3.0 cc/g dry polymer.
Cross-linked polymer derived from specified polymerizable monomers
The sorbent comprises cross-linked polymeric material derived from the reaction of a cross-linker with one or more polymerizable monomers including divinyl-benzene, styrene, ethylstyrene, acrylonitrile, butyl methacrylate, octyl methacrylate, butyl acrylate, octyl acrylate, cetyl methacrylate, cetyl acrylate, ethyl methacrylate, ethyl acrylate, vinyltoluene, vinylnaphthalene, vinylbenzyl alcohol, vinylformamide, methyl methacrylate, and methyl acrylate.
Overall, the claim coverage centers on removing undesirable molecules from a physiologic fluid with a cross-linked polymer sorbent bearing surface-attached zwitterionic ligands, administered orally or rectally, and constrained by specified particle diameter and pore-structure characteristics, with the cross-linked polymer derived from selected polymerizable monomers.
Stated Advantages
Improves hemocompatibility-related performance by using a polymer characterized as hemocompatible.
Provides non-thrombogenicity and reduced fouling.
Removes undesirable molecules associated with stored blood and blood products, and demonstrates removal of cytochrome C and human serum albumin.
Documented Applications
Removal of undesirable molecules from physiologic fluid by contacting the physiologic fluid with the sorbent.
Oral or rectal administration of the sorbent as part of removing undesirable molecules from physiologic fluid.
Purification of blood/physiologic fluid for blood products, including addressing undesirable molecules associated with stored blood and blood products.
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