IP Library Granted Patent US 11,752,250
Granted Patent B2
US 11,752,250 · App. 14/230,108 · Granted Sep 12, 2023

Hemocompatibility modifiers for cross-linked polymeric material

Inventors: Thomas D. Golobish (Princeton, NJ); Vincent J. Capponi (Monmouth Junction, NJ); David R. Clay (West Orange, NJ)
Assignee: CytoSorbents Corporation
A61M1/3679A01N1/02A01N1/0215A61M1/0272A61M1/34A61M1/36B01J20/261B01J20/267B01J20/28069B01J20/28078B01J20/28092B01J20/3208B01J20/3246B01J20/3248B01J20/3251B01J20/3272B01J20/3282B01J20/3285B01J2220/62
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Quick Facts
Patent No.
US 11,752,250
App. No.
14/230,108
Granted
Sep 12, 2023
Kind
B2
Abstract

The invention concerns methods of treating blood, blood product, or physiologic fluid to provide at least one of (i) increasing shelf life of the blood, blood product or physiologic fluid, (ii) maintaining freshness of new blood, blood product or physiologic fluid, and (iii) removing undesirable molecules from the blood, blood product or physiologic fluid; said method comprising contacting said blood, blood product or physiologic fluid with a sorbent, said sorbent being primarily in a plurality of solid forms and comprising a cross-linked polymeric material having a plurality of at least one of (1) zwitterionic moieties and (2) oligo(ethylene glycol) moieties attached to the surface of said cross-linked polymeric material.

Claims (19)

1. A method of treating blood, blood product, plasma or physiologic fluid to provide increased shelf life of the blood, blood product or physiologic fluid; said method comprising contacting said blood, blood product 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 inflammatory mediators and stimulators when said sorbent is (a) within a cartridge suitable for filtration of blood, blood product or physiologic fluid, (b) placed within a storage bag suitable for storing blood, blood product or physiologic fluid;

wherein said sorbent comprises particles having a diameter in the range for 0.1 micron meters to 2 centimeters,

wherein said particles are characterized as having a pore structure having a total volume of pore sizes in the range of from 10 Å to 10,000 Å that is between (a) greater than 0.5 cc/g dry polymer and (b) 3.0 cc/g dry polymer; wherein the ratio of pore volume between 10 Å to 3,000 Å in diameter to pore volume between 500 Å to 3,000 Å in diameter of the said cross-linked polymeric material is smaller than 7:1 and wherein the ratio of pore volume between 10 Å to 3,000 Å in diameter to pore volume between 10 Å to 6,000 Å in diameter of said cross-linked polymeric material is less than 2:1 and

wherein when said sorbent is contained within said cartridge or said storage bag, said sorbent being substantially free-flowing within said cartridge or said storage bag; and

wherein the inflammatory mediators and stimulators are selected from cytokines, thromboxanes, leukotrienes, platelet-activating factor, prostaglandins, glycoproteins, kinins, kininogens, complement factors, cell-adhesion molecules, superantigens, monokines, chemokines, interferons, free radicals, proteases, arachidonic acid metabolites, prostacyclins, beta endorphins, myocardial depressant factors, tetrahydrobiopterin, bradykinin, soluble CD40 ligand, hemoglobin, red cell particulates, membrane or cellular components, growth factors, prions, toxins, endotoxins, vasoactive substances, foreign antigens, microvesicles and antibodies;

wherein said sorbent comprises cross-linked polymeric material derived from the reaction of a cross-linker with one or more of the following polymerizable monomers: 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; and

wherein said zwitterionic moieties comprise one or more carboxybetaine and sulfobetaine zwitterionic moieties.

2. The method of claim 1 , wherein said zwitterionic moieties comprise at least one residue of carboxybetaine methacrylate.

3. The method of claim 1 , wherein said zwitterionic moieties comprise at least one group of the formula

4. The method of claim 1 , wherein the inflammatory mediators and stimulators are antibodies.

5. The method of claim 1 , wherein said zwitterionic moieties are covalently bonded to the surface of said cross-linked polymeric material.

6. The method of claim 1 , wherein said zwitterionic moieties are covalently bound to the surface of said cross-linked polymeric material by radical polymerization of ethylenically unsaturated zwitterionic monomers having a sulphobetaine group with an unsaturated group residing on the surface of said cross-linked polymeric material.

7. The method of claim 1 , wherein said sorbent is a biocompatible polymer.

8. The method of claim 1 , wherein said polymer is hemocompatible.

9. The method of claim 1 , wherein said particles comprise a carboxybetaine methacrylate coating.

10. The method of claim 1 , wherein the zwitterionic moieties are selected from:

11. The method of claim 1 , wherein the inflammatory mediators and stimulators comprise cytokines.

12. The method of claim 1 , wherein the oligo(ethylene glycol) moieties comprise at least one group of the formula:

where n is an integer from 3-8.

Assignments (4)
SECURITY INTEREST Recorded Jun 28, 2024
From: CYTOSORBENTS CORPORATION
To: AVENUE CAPITAL MANAGEMENT II, L.P.
Reel/Frame 067964/0382 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 7, 2017
From: CYTOSORBENTS, INC.
To: CYTOSORBENTS CORPORATION
Reel/Frame 044698/0348 →
CONFIRMATORY LICENSE Recorded Oct 6, 2017
From: CYTOSORBENTS, CORPORATION
To: UNITED STATES OF AMERICA AS REPRESENTED BY THE SECRETARY OF THE NAVY
Reel/Frame 044144/0545 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 20, 2014
From: GOLOBISH, THOMAS D.; CAPPONI, VINCENT J.; CLAY, DAVID R.
To: CYTOSORBENTS CORPORATION
Reel/Frame 034218/0167 →
Continuity (2)
Provisional Application 61806990 · Apr 1, 2013
Related Publication 20140294751A1 · Oct 2, 2014