Biocompatible devices, systems, and methods for reducing levels of pro-inflammatory or anti-inflammatory stimulators or mediators in the blood

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.

We claim:  
     
         1 . A device for removing cytokines or other species of pro-inflammatory or anti-inflammatory stimulators or mediators from the blood comprising a housing, and an adsorption medium in the housing sized to selectively adsorb cytokines or other species of pro-inflammatory or anti-inflammatory stimulators or mediators from the blood, the adsorption medium being characterized by a Biocompatibility Index of not greater than 14.  
     
     
         2 . A device for removing cytokines or other species of pro-inflammatory or anti-inflammatory stimulators or mediators from a blood component product harvested from the blood drawn from an individual comprising a housing, and an adsorption medium in the housing sized to selectively adsorb cytokines or other species of pro-inflammatory or anti-inflammatory stimulators or mediators from the blood component product, the adsorption medium being characterized by a Biocompatibility Index of not greater than 14.  
     
     
         3 . A device for removing cytokines or other species of pro-inflammatory or anti-inflammatory stimulators or mediators from a physiologic fluid drawn from an individual comprising a housing, and an adsorption medium in the housing sized to selectively adsorb cytokines or other species of pro-inflammatory or anti-inflammatory stimulators or mediators from the physiologic fluid, the adsorption medium being characterized by a Biocompatibility Index of not greater than 14.  
     
     
         4 . A device according to  claim 1  or  2  or  3  
 wherein the Biocompatibility Index is not greater than 7.  
 
     
     
         5 . A system according to  claim 1  or  2  or  3  
 wherein the adsorption medium comprises a polymeric material.  
 
     
     
         6 . A system according to  claim 5   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 of 2-hydroxyethyl methacrylate, N-vinylpyrrolidine, N-vinylcaprolactame and N-acrylamide.    
     
     
         7 . A system for treating an individual experiencing septic shock comprising a flow path adapted to draw the blood from the circulatory system of the individual for return to the circulatory system including an adsorption medium sized to selectively adsorb cytokines or other species of pro-inflammatory or anti-inflammatory stimulators or mediators from the blood, the adsorption medium being characterized by a Biocompatibility Index of not greater than 14.  
     
     
         8 . A system according to  claim 7   wherein the Biocompatibility Index is not greater than 7.    
     
     
         9 . A system according to  claim 7   wherein the adsorption medium comprises a polymeric material.    
     
     
         10 . A system according to  claim 9   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 of 2-hydroxyethyl methacrylate, N-vinylpyrrolidine, N-vinylcaprolactame and N-acrylamide.    
     
     
         11 . A system according to  claim 7   wherein the flow path includes an intravenous catheter.    
     
     
         12 . A system according to  claim 7   wherein the flow path includes an indwelling catheter.    
     
     
         13 . A system according to  claim 7   wherein the flow path includes tubing having a wall impregnated with the adsorption medium.    
     
     
         14 . A system according to  claim 7   wherein the flow path includes an in-line housing, and    wherein the adsorption medium is contained within the housing.    
     
     
         15 . A system according to  claim 7   wherein the flow path includes an in-line exchangeable housing, and    wherein the adsorption medium is contained within the housing.    
     
     
         16 . A system for treating the blood of an individual comprising 
 means for drawing the blood from the circulatory system of the individual for return to the circulatory system, and    means for removing cytokines or other species of pro-inflammatory or anti-inflammatory stimulators or mediators from the blood by bringing the blood into contact with an adsorption medium sized to selectively adsorb cytokines from the blood, the adsorption medium being characterized by a Biocompatibility Index of not greater than 14.    
     
     
         17 . A system according to  claim 16   wherein the Biocompatibility Index is not greater than 7.    
     
     
         18 . A system according to  claim 16   wherein the adsorption medium comprises a polymeric material.    
     
     
         19 . A system according to  claim 18   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 of 2-hydroxyethyl methacrylate, N-vinylpyrrolidine, N-vinylcaprolactame and N-acrylamide.    
     
     
         20 . A system according to  claim 16   wherein the means for drawing the blood includes an intravenous catheter.    
     
     
         21 . A system according to  claim 16   wherein the means for drawing the blood includes an indwelling catheter.    
     
     
         22 . A system according to  claim 16   wherein the means for drawing the blood includes tubing having a wall impregnated with the adsorption medium.    
     
     
         23 . A system according to  claim 16   wherein the means for drawing the blood includes an in-line housing, and    wherein the adsorption medium is contained within the housing.    
     
     
         24 . A system according to  claim 16   wherein the means for drawing the blood includes an in-line exchangeable housing, and    wherein the adsorption medium is contained within the housing.    
     
     
         25 . A method for treating the blood of an individual comprising the steps of 
 drawing the blood from the circulatory system of the individual for return to the circulatory system, and    removing cytokines or other species of pro-inflammatory or anti-inflammatory stimulators or mediators from the blood by bringing the blood into contact with an adsorption medium sized to selectively adsorb cytokines or other species of pro-inflammatory or anti-inflammatory stimulators or mediators from the blood, the adsorption medium being characterized by a Biocompatibility Index of not greater than 14.    
     
     
         26 . A method according to  claim 25   wherein the Biocompatibility Index is not greater than 7.    
     
     
         27 . A method according to  claim 25   wherein the adsorption medium comprises a polymeric material.    
     
     
         28 . A method according to  claim 27   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 of 2-hydroxyethyl methacrylate, N-vinylpyrrolidine, N-vinylcaprolactame and N-acrylamide.    
     
     
         29 . A method for treating an individual experiencing a condition on a continuum from early sepsis to septic shock comprising the steps of 
 drawing the blood from the circulatory system of the individual for return to the circulatory system, and    removing cytokines or other species of pro-inflammatory or anti-inflammatory stimulators or mediators from the blood by bringing the blood into contact with an adsorption medium sized to selectively adsorb cytokines or other species of pro-inflammatory or anti-inflammatory stimulators or mediators from the blood, the adsorption medium being characterized by a Biocompatibility Index of not greater than 14.    
     
     
         30 . A method according to  claim 29   wherein the Biocompatibility Index is not greater than 7.    
     
     
         31 . A system according to  claim 29   wherein the adsorption medium comprises a polymeric material.    
     
     
         32 . A system according to claim  31   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 of 2-hydroxyethyl methacrylate, N-vinylpyrrolidine, N-vinylcaprolactame and N-acrylamide.