Methods for removing cytokines from blood with surface immobilized polysaccharides
Inventors
Ward, Robert S. • McCrea, Keith R. • Larm, Olle • Adolfsson, Lars
Assignees
EXTHERA MEDICAL LLC • Exthera Medical Corp
Publication Number
US-11123466-B2
Publication Date
2021-09-21
Expiration Date
2030-12-01
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Abstract
The present invention is directed to a method for removing cytokines and/or pathogens from blood or blood serum (blood) by contacting the blood with a solid, essentially non microporous substrate which has been surface treated with heparin, heparan sulfate and/or other molecules or chemical groups (the adsorbent media or media) having a binding affinity for the cytokine or pathogen(s) to be removed (the adsorbates), and wherein the size of the interstitial channels within said media is balanced with the amount of media surface area and the surface concentration of binding sites on the media in order to provide adequate adsorptive capacity while also allowing relatively high flow rates of blood through the adsorbent media.
Core Innovation
The invention relates to methods and devices for removing cytokines and/or pathogens from blood by using a solid, essentially non-microporous substrate surface-treated with polysaccharides such as heparin, heparan sulfate, or other molecules with binding affinity for the target cytokines or pathogens. The adsorbent media are engineered so that the size of their interstitial channels is balanced with overall surface area and the concentration of binding sites, allowing high adsorptive capacity at relatively high flow rates typical of clinical extracorporeal blood circuits.
This approach addresses the problem of conventional porous adsorbent media which rely on slow molecular diffusion for adsorbate transport, requiring very low flow rates that are impractical or unsafe for clinical blood treatment. The present invention instead uses primarily forced convection to deliver adsorbates to binding sites, providing rapid and efficient separation while enabling safe operational blood flow velocities and minimizing pressure drop and blood cell damage.
The method and corresponding devices are suitable for both treating existing diseases by removing cytokines and/or pathogens from patient blood and for prophylactic use, such as during blood collection or transfusion, to reduce or prevent the spread of disease. The invention includes a variety of substrate forms, such as rigid polymer beads, fibers, reticulated foams, and spiral-wound dense membranes, all designed to optimize surface exposure and blood compatibility, and allows for the inclusion of multiple adsorbent chemistries to target diverse pathogenic entities.
Claims Coverage
The patent includes two independent claims, covering a device and a method for removing cytokines, pathogens, and toxins from blood using solid substrates with immobilized polysaccharide adsorbents.
Device for removing cytokines, pathogens, and toxins using solid substrate with polysaccharide adsorbent
A device comprising: - A container containing a solid substrate of high surface area with at least one polysaccharide adsorbent on its surface, having binding affinity for cytokines, pathogens, or toxins. - The polysaccharide includes a carbohydrate with mannose sequences. - The solid substrate has interstitial channel spaces large enough to allow transport of blood cells. - During blood flow, the adsorbates bind to the binding sites on the polysaccharide adsorbent, becoming separated from the blood. - Transport of adsorbates from blood to adsorbent sites on the substrate is primarily by convection transport.
Method for removing cytokines, pathogens, and toxins using a high surface area polysaccharide-coated substrate
A method comprising: - Contacting blood with a device containing a solid substrate of high surface area with at least one polysaccharide adsorbent having binding affinity for the adsorbate. - The polysaccharide adsorbent comprises a carbohydrate with mannose sequences. - The solid substrate has interstitial channel spaces large enough to allow transport of blood cells. - During blood flow, adsorbates bind to the binding sites on the polysaccharide adsorbent and are removed from the blood. - The transport of adsorbates from blood to adsorbent sites is primarily by convection transport.
The inventive features focus on devices and methods utilizing high surface area solid substrates with immobilized, select polysaccharide adsorbents for the forced convection-based removal of cytokines, pathogens, and toxins from blood.
Stated Advantages
Provides clinically relevant adsorptive capacity at high flow rates typical of extracorporeal blood circuits, improving treatment efficiency and safety.
Reduces the risk of blood clot formation by allowing high blood flow and minimizing stagnation compared to diffusive, porous media.
Eliminates bleeding complications associated with free systemic heparin by using immobilized heparin on a solid substrate.
Allows rapid and efficient removal of large proteins and pathogens from blood due to dominant convection kinetics.
Reduces or eliminates the spread of disease during blood collection or transfusion by removing pathogens and cytokines.
Enables multifunctional removal of various compounds, including cytokines, endotoxins, and certain bacteria, by combining different adsorbent chemistries.
Documented Applications
Treatment of diseases characterized by elevated blood cytokines or pathogens, including sepsis and immune-mediated conditions.
Use during collection or transfusion of banked blood to reduce or eliminate the spread of disease.
Application in extracorporeal blood circuits such as dialysis, cardiopulmonary bypass, and extracorporeal membrane oxygenation.
Use for removing specific pathogens (e.g., viruses, bacteria, parasites) from blood as listed in the detailed description.
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