US 7,312,023 B2 · Devices, systems, and methods for reducing levels of pro-inflammatory or anti-inflammatory stimulators or mediators in the blood, generated as a result of extracorporeal blood processing

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.

A blood processing method comprising

selecting for use 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 heperinized blood heperinized 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
The Biocompatibility Index Score Table
Numeric Scores
1
2
3
(Signifying
(Signifying
(Signifying
Most
an
a Least
Desired
Acceptable
Desired
Degree of
Degree of
Degree of
Blood
Biocompati-
Biocompati-
Biocompati-
Indicator
bility)
bility)
bility)
Loss of White
Maximum
Maximum
Maximum
Blood Cells
Difference
Difference
Difference
Between
Between
Between
Baseline
Baseline and
Baseline and
and Medium
Medium (25
Medium (25
(25 ml)
ml)
ml)
≦15%
>15%
>20%
≦20%
Loss of Red
Maximum
Maximum
Maximum
Blood Cells
Difference
Difference
Difference
Between
Between
Between
Baseline
Baseline and
Baseline and
and Medium
Medium (25
Medium (25
(25 ml)
ml)
ml)
≦15%
>15%
>20%
≦20%
Loss of
Maximum
Maximum
Maximum
Platelets
Difference
Difference
Difference
Between
Between
Between
Baseline
Baseline and
Baseline and
and Medium
Medium (25
Medium (25
(25 ml)
ml)
ml)
≦15%
>15%
>20%
≦20%
PMN Elastase
Maximum
Maximum
Maximum
Concentration
Difference
Difference
Difference
Between
Between
Between
Baseline
Baseline and
Baseline and
and Medium
Medium (25
Medium (25
(25 ml)
ml)
ml)
≦15%
>15%
>20%
≦20%
LDH
Maximum
Maximum
Maximum
Concentration
Difference
Difference
Difference
Between
Between
Between
Baseline
Baseline and
Baseline and
and Medium
Medium (25
Medium (25
(25 ml)
ml)
ml)
≦15%
>15%
>20%
≦20%
C3a-desArg
Maximum
Maximum
Maximum
Concentration
Difference
Difference
Difference
Between
Between
Between
Baseline
Baseline and
Baseline and
and Medium
Medium (25
Medium (25
(25 ml)
ml)
ml)
≦20%
>20%
>25%
≦25%
TAT
Maximum
Maximum
Maximum
Concentration
Difference
Difference
Difference
Between
Between
Between
Baseline
Baseline and
Baseline and
and Medium
Medium (25
Medium (25
(25 ml)
ml)
ml)
≦15%
>15%
>20%
≦20%
(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,
conveying blood drawn from an individual to an extracorporeal centrifugal blood separation apparatus,
operating the extracorporeal centrifugal blood separation apparatus to conduct centrifugal separation of a blood component from the blood, the centrifugal separation triggering an incidental generation of cytokines in the blood component,
removing from the blood component the cytokines that are generated as a result of the centrifugal separation of the blood comprising passing the blood component through the absorption medium.

204 more elements

Devices, systems, and methods for reducing levels of pro-inflammatory or anti-inflammatory stimulators or mediators in the blood, generated as a result of extracorporeal blood processing

Life of this patent

Devices, systems, and methods for reducing levels of pro-inflammatory or anti-inflammatory stimulators or mediators in the blood, generated as a result of extracorporeal blood processing

Life of this patent

Abstract

Claims7