Adsorbing pathogen-inactivating compounds with porous particles immobilized in a matrix

Abstract

Methods and devices are provided for reducing the concentration of low molecular weight compounds in a biological composition containing cells while substantially maintaining a desired biological activity of the biological composition. The device comprises highly porous adsorbent particles, and the adsorbent particles are immobilized by an inert matrix.

1 . A device for reducing the concentration of a low molecular weight compound in a biological composition containing cells, wherein the device comprises an inert matrix containing highly adsorbent particles, and wherein the diameter of the adsorbent particles ranges from about 100 μm to about 1500 μm, and wherein the cells in the biological composition treated with the device substantially maintain their desired biological activity, and wherein the device is for use in a batch process.  
     
     
         2 . A device according to  claim 1  further comprising a container that is compatible with the biological composition.  
     
     
         3 . A device according to  claim 1 , wherein the adsorbent particles have a surface area greater than about 750 m 2 /g.  
     
     
         4 . A device according to  claim 3 , wherein the adsorbent particles have a surface area between about 1000 m 2 /g and 3000 m 2 /g.  
     
     
         5 . A device according to  claim 1 , wherein the adsorbent particles are polyaromatic adsorbent particles.  
     
     
         6 . A device according to  claim 5 , wherein the polyaromatic adsorbent particles possess superior wetting properties.  
     
     
         7 . A device according to  claim 5 , wherein the polyaromatic adsorbent particles comprise a hypercrosslinked polystyrene network.  
     
     
         8 . A device according to  claim 1 , wherein the adsorbent particles are activated carbon particles.  
     
     
         9 . A device according to  claim 8 , wherein the activated carbon particles are derived from a synthetic source.  
     
     
         10 . A device according to  claim 9 , wherein the low molecular weight compound is a quencher.  
     
     
         11 . A device according to  claim 9 , wherein the activated carbon particles are roughly spherical and are of a diameter ranging from about 300 μm to about 900 μm.  
     
     
         12 . A device selected from devices according to  claim 1 ,  5  or  8 , wherein the inert matrix is a synthetic polymer fiber.  
     
     
         13 . A device according to  claim 12 , wherein the synthetic polymeric fiber comprises a polymer core with a high melting temperature surrounded by a sheath with a lower melting temperature.  
     
     
         14 . A device according to  claim 12 , wherein the inert matrix is a particulate network.  
     
     
         15 . A device according to  claim 14 , wherein the particulate network comprises polyethylene particles.  
     
     
         16 . A device according to  claim 1 , wherein the adsorbent particles are immobilized in the matrix.  
     
     
         17 . A device according to  claim 1 , wherein the low molecular weight compound is a nucleic acid targeting agent or a photosensitizer.  
     
     
         18 . A device according to  claim 1 , wherein the low molecular weight compound is an acridine derivative, a psoralen derivative or a dye.  
     
     
         19 . A device according to  claim 1 , wherein the low molecular weight compound is a biological response modifier.  
     
     
         20 . A device according to  claim 19 , wherein the biological response modifier is activated complement.  
     
     
         21 . A device according to  claim 1 , wherein the low molecular weight compound is a quencher.  
     
     
         22 . A device according to  claim 1 , wherein the low molecular weight compound is a polyamine derivative.  
     
     
         23 . A device according to  claim 1 , wherein the desired biological activity maintained by the cells is suitability for infusion.  
     
     
         24 . A device according to  claim 1 , wherein the biological composition comprises platelets.  
     
     
         25 . A device according to  claim 24 , wherein treatment of the biological composition with a device over a period of about 5 days results in less than about a 10% loss in platelet count.  
     
     
         26 . A device according to  claim 25 , wherein the device further comprises a container that is compatible with the biological composition, and wherein the inert matrix is a synthetic polymer fiber comprising a polymer core with a high melting point surrounded by a sheath with a lower melting temperature, and wherein the adsorbent particles are polyaromatic adsorbents comprising a hypercrosslinked polystyrene network, and wherein the surface area of the particles is greater than about 750 m 2 /g, and wherein the adsorbent particles are immobilized in the matrix.  
     
     
         27 . A device according to  claim 26 , wherein the desired biological activity maintained by the cells is suitability for infusion.  
     
     
         28 . A device according to  claim 27 , wherein the biological composition is treated with the device at a temperature of about 22° C. for between 0.5 hour and 7 days.  
     
     
         29 . A device according to  claim 26 , wherein the low molecular weight compound is an acridine derivative, a psoralen derivative or a dye.  
     
     
         30 . A device according to  claim 26 , wherein the low molecular weight compound is a biological response modifier.  
     
     
         31 . A device according to  claim 30 , wherein the biological response modifier is activated complement.  
     
     
         32 . A device according to  claim 1 , wherein the biological composition comprises red blood cells.  
     
     
         33 . A device according to  claim 32 , wherein treatment of the biological composition with the device over a period of up to 35 days results in less than about 1% hemolysis.  
     
     
         34 . A device according to  claim 33 , wherein the device further comprises a container that is compatible with the biological composition, and wherein the inert matrix is a synthetic polymer fiber comprising a polymer core with a high melting point surrounded by a sheath with a lower melting temperature, and wherein the adsorbent particles are activated carbon particles derived from a synthetic source, and wherein the diameter of the particles ranges from about 300 μm to about 900 μm, and wherein the surface area of the particles is greater than about 750 m 2/ g, and wherein the adsorbent particles are immobilized in the matrix.  
     
     
         35 . A device according to  claim 34 , wherein the desired biological activity maintained by the cells is suitability for infusion.  
     
     
         36 . A device according to  claim 34 , wherein the low molecular weight compound is an acridine derivative, a psoralen derivative or a dye.  
     
     
         37 . A device according to  claim 34 , wherein the low molecular weight compound is a biological response modifier.  
     
     
         38 . A device according to  claim 37 , wherein the biological response modifier is activated complement.  
     
     
         39 . A method for reducing the concentration of a low molecular weight compound in a biological composition containing cells comprising treating the biological composition with a device of  claim 1  or  34  for between 0.5 hour and 5 weeks, wherein the cells in the biological composition treated with the device substantially maintain their desired biological activity.  
     
     
         40 . A method according to  claim 39 , wherein the cells in the biological composition treated with the device substantially maintain their desired biological activity after being treated with the device for between 1.0 hour and 5 weeks.  
     
     
         41 . A method according to  claim 39 , wherein the low molecular weight compound is an acridine derivative.  
     
     
         42 . A method according to  claim 39 , wherein the low molecular weight compound is a psoralen derivative.  
     
     
         43 . A method according to  claim 39 , wherein the low molecular weight compound is a dye.  
     
     
         44 . A method according to  claim 39 , wherein the low molecular weight compound is a biological response modifier.  
     
     
         45 . A method according to  claim 44 , wherein the biological response modifier is activated complement.  
     
     
         46 . A method according to  claim 39 , wherein the biological composition is first treated with the device at a temperature of about 22° C. for between about 0.5 and about 36 hours.  
     
     
         47 . A method according to  claim 39 , wherein the biological composition is first treated with the device at a temperature of about 22° C. for between about 0.5 and about 24 hours.  
     
     
         48 . A method according to  claim 39 , wherein the biological composition is first treated with the device at a temperature of about 22° C. for between about 0.5 and about 12 hours.  
     
     
         49 . A method according to  claim 47 , wherein the blood product i s subsequently treated with the device at a temperature of about 4° C. for up to 5 weeks.  
     
     
         50 . A biological composition containing cells, wherein the biological composition is suitable for infusion, and wherein the biological composition is produced by treating a biological composition containing cells with a device according to  claim 1  or  34  for a period between about 0.5 hour and 5 weeks.  
     
     
         51 . A device for reducing the concentration of small organic compounds in a blood product while substantially maintaining a desired biological activity of the blood product, the device comprising highly porous adsorbent particles, wherein the adsorbent particles are immobilized by an inert matrix.  
     
     
         52 . A method for reducing the concentration of a low molecular weight compound in a biological composition containing cells comprising treating the biological composition with a device according to  claim 26  for between about 0. 5 hours and about 7 days, wherein the cells in the biological composition treated with the device substantially maintain their desired biological activity.