# US 8,349,550 B2 · Methods for reducing levels of pro-inflammatory or anti-inflammatory stimulators or mediators in the blood

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- Number: US 8,349,550 B2
- Document ID: US8349550B2
- Status: Granted
- Kind: B2
- Application number: 12/928,058
- Filed: 2010-12-02
- Published: 2011-04-28
- Granted: 2013-01-08
- Earliest claimed: 1997-07-30
- Assignees: CytoSorbents Corporation; Stefen Brodie; Donald Brodie
- Inventors: James A Brady; James F Winchester; Vadim Davankov; Maria Tsvurupa; Ludmila Pavlova; Frank M Norris; Peter J Quartararo, Jr.; Jamie A Salsberg
- Web page: https://patentgrep.com/patent/US8349550B2

## CPC

- A61M 1/3679: {by absorption (A61M1/3675 takes precedence)}
- A01N 1/124: Disinfecting agents, e.g. antimicrobials
- A61M 1/28: Peritoneal dialysis {; Other peritoneal treatment, e.g. oxygenation}
- A61M 1/3403: {Regulation parameters}
- B01J 20/26: Synthetic macromolecular compounds
- B01J 20/261: {obtained by reactions only involving carbon to carbon unsaturated bonds (macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds per se C08F)}
- B01J 20/264: {derived from different types of monomers, e.g. linear or branched copolymers, block copolymers, graft copolymers}
- B01J 20/267: {Cross-linked polymers}
- B01J 20/28078: {Pore diameter}
- B01J 20/3064: {Addition of pore forming agents, e.g. pore inducing or porogenic agents}
- B01J 20/321: {consisting of a polymer obtained by reactions involving only carbon to carbon unsaturated bonds}
- B01J 20/327: {Polymers obtained by reactions involving only carbon to carbon unsaturated bonds}
- B01J 20/3276: {Copolymers}
- B01J 20/3293: {Coatings on a core, the core being particle or fiber shaped, e.g. encapsulated particles, coated fibers}
- C07K 14/745: Blood coagulation or fibrinolysis factors
- A61M 1/16: with membranes
- A61M 1/1698: {Blood oxygenators with or without heat-exchangers (intracorporal A61M1/1678; manufacturing of membranes therefor B01D67/00; semi-permeable membranes for separation processes characterised by their properties B01D69/00; semi-permeable membranes characterised by their material B01D71/00)}
- A61M 1/34: Filtering material out of the blood by passing it through a membrane, i.e. hemofiltration or diafiltration
- A61M 1/3486: {Biological, chemical treatment, e.g. chemical precipitation; treatment by absorbents}
- A61M 1/3496: {Plasmapheresis; Leucopheresis; Lymphopheresis (A61M1/3472 takes precedence)}
- A61M 1/38: Removing constituents from donor blood and {storing or} returning remainder to body {, e.g. for transfusion}
- A61M 2202/0421: Beta-2-microglobulin
- A61M 2205/3331: Pressure; Flow
- B01J 2220/445: comprising a mixture of polymers
- B01J 2220/603: serially disposed columns
- A61M: DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY (introducing media into or onto the bodies of animals A61D7/00; means for inserting tampons A61F13/26; devices for administering food or medicines orally A61J; containers for collecting, storing or administering blood or medical fluids A61J1/05); DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY (surgery A61B; chemical aspects of surgical articles A61L); DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR {(Electrotherapy, e.g. producing anaesthesia by the use of alternating or intermittent currents A61N1/36021)}
- A01N: PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF (preservation of food or foodstuff A23); BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES (preparations for medical, dental or toiletry purposes which kill or prevent the growth or proliferation of unwanted organisms A61K); PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- B01J: CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)

## Abstract

Devices, systems, and methods reduce levels of pro-inflammatory or anti-inflammatory stimulators or mediators in blood by selective adsorption. The devices, systems, and methods are useful in situations where abnormal levels of or unregulated or excessive interaction among pro-inflammatory or anti-inflammatory stimulators or mediators occur, or during events that do induce or have the potential for inducing abnormal production of pro-inflammatory or anti-inflammatory stimulators or mediators. The devices, systems, and methods serve to prevent, control, reduce, or alleviate the severity of the inflammatory response and disease states that are associated with abnormal levels of or unregulated or excessive interaction among pro-inflammatory or anti-inflammatory stimulators or mediators.

## Claims

### Claim 1

A method for storing an organ harvested for transplantation comprising
placing the organ in a preservation solution for storage prior to transplantation, and during storage,
removing cytokines from the preservation solution by bringing the preservation solution into contact with an adsorption medium comprising a group of polymeric particles each comprising a hydrophobic core and a biocompatible hydrophilic coating, the adsorption medium selected to have a Biocompatibility Index of not greater than 14 derived by a protocol consisting essentially of:
(i) selecting blood indicators which quantify, physiologic changes based upon contact between the adsorption medium and blood, the blood indicators consisting essentially of
(1) white blood cell count diminution as a result of contact with the adsorption medium ascertained by Coulter Counter;
(2) red blood cell count diminution as a result of contact with the adsorption medium ascertained by Coulter Counter;
(3) platelet count diminution as a result of contact with the adsorption medium ascertained by Coulter Counter;
(4) leukocytes activation as a result of contact with the adsorption medium ascertained by measuring polymorphonuclear leukocyte elastase concentration (PMN Elastase Concentration);
(5) complement activation as a result of contact with the adsorption medium ascertained by measuring anaphylatoxin C3a-desArg concentrations;
(6) occurrence of hemolysis as a result of contact with the adsorption medium ascertained by determining concentrations of Lactate dehydrogenase (LDH); and reduction of clot formation as a result of contact with the adsorption medium ascertained by measuring concentrations of thrombin-antithrombin-complex (TAT),
(ii) for each indicator, ascertaining a maximum difference between the indicator values over 25 ml of flow of heparinized blood heparinized to a final concentration of 1.0 IU heparin/ml blood passed through a biocompatible housing without the adsorption medium, comprising a baseline value, and heparinized blood passed through the housing containing the adsorption medium, and for each indicator, expressing the maximum change as a percentage change, relative to the baseline value,
(iii) scoring the percentage change for each indicator as a dimensionless numeric quantity 1, 2, or 3, depending upon the magnitude of the percentage change, in accordance with Table 1,
(iv) after scoring each indicator with a numeric quantity of 1, 2, or 3, adding the numeric quantities scored for all the indicators to obtain a total, the total comprising the Biocompatibility Index.

### Claim 2 (depends on 1)

A method according to claim 1 wherein the Biocompatibility Index is not greater than 7.

### Claim 3 (depends on 1)

A method according to claim 1 wherein the polymeric material comprises
particles formed from a porous hydrophobic divinylbenzene copolymer having a surface modified to include surface exposed functional groups selected from the group of polymers consisting of: 2-hydroxyethyl methacrylate, and N-vinylpyrrolidine.