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-10086126-B2
Publication Date
2018-10-02
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 present invention provides a method for the removal of cytokines and/or pathogens from blood by contacting the blood with a solid, essentially non-microporous substrate that has been surface treated with heparin, heparan sulfate, or other molecules with a binding affinity for the targeted cytokines or pathogens. The solid substrate is engineered so that its interstitial channel size is balanced with surface area and the concentration of binding sites, achieving high adsorptive capacity while permitting relatively high blood flow rates through the media. This approach ensures that transport of adsorbates to the binding sites primarily occurs by forced convection, rather than the much slower diffusion processes typical in microporous media.
The patent addresses the problem of elevated cytokine and/or pathogen concentrations in blood, which are characteristic of a variety of disease conditions. Existing removal strategies frequently rely on porous adsorbent media that necessitate low flow rates to be effective, resulting in slow molecular diffusion and potential complications such as clot formation due to blood stasis. The invention circumvents these limitations by employing a nonporous, high-surface area substrate with immobilized adsorbents, facilitating rapid removal of harmful substances from blood or serum under clinically relevant, high flow conditions.
The method can be applied for therapeutic or prophylactic purposes, such as during blood transfusion or direct treatment of patients suffering from diseases characterized by undesirable cytokine or pathogen presence. The system is adapted for integration into extracorporeal blood circuits commonly used in clinical settings, including dialysis, cardiopulmonary bypass, and extracorporeal membrane oxygenation, providing a safe and efficient technique for selective adsorption and removal of disease-contributing blood components without introducing free, systemic heparin and its associated risks.
Claims Coverage
There are two independent claims, each defining core inventive features related to an extracorporeal cartridge utilizing heparinized and cationic media for adsorbate removal.
Cartridge with heparinized media and cationic, more thrombogenic media
A cartridge for extracorporeal removal of at least one adsorbate comprising: - A first media that is heparinized, enabling binding and removal of cytokines or pathogens from blood. - A second media, which is cationic and more thrombogenic than the first media, providing additional adsorption functionality (such as endotoxin removal). - The cartridge may contain further inventive arrangements (as in dependent claims), such as layering, blending, bead composition, coating with specific agents (e.g., PEI, chitosan, sialic acid), ratios, and inclusion of a third media (e.g., mannose-functionalized beads).
Cartridge adapted for extracorporeal blood circuit with heparinized and cationic, more thrombogenic media
A cartridge specifically adapted for use in an extracorporeal blood circuit, comprising: - A first media being heparinized media for adsorption of targeted blood-borne substances. - A second media that is cationic and more thrombogenic than the first media, intended to complement the adsorption profile of the cartridge.
The inventive features are focused on the construction of a cartridge utilizing both heparinized media and cationic, more thrombogenic media, with flexibility in their arrangement and adaptation for efficient extracorporeal removal of adsorbates.
Stated Advantages
Enables removal of cytokines and/or pathogens from blood at relatively high flow rates, allowing clinically relevant flow in extracorporeal blood circuits.
Provides rapid and efficient adsorptive capacity by relying on forced convection transport instead of slower diffusion-based methods.
Reduces or eliminates the risk of bleeding complications since no free, systemic heparin is required for efficacy; heparin is immobilized on the substrate.
Offers improved safety and biocompatibility by maintaining high flow rates that reduce stagnation and clot formation in blood contacting devices.
Facilitates selective removal of a range of target molecules, including cytokines, pathogens, endotoxins, and even specific bacteria, by enabling mixed or layered media functionality.
Provides a stable coating with no clinically significant leakage of carbohydrate into the blood during use.
Documented Applications
Therapeutic removal of cytokines and/or pathogens from mammalian blood in patients suffering from diseases such as sepsis or other conditions with elevated cytokines or pathogens.
Prophylactic use during blood collection, transfusion of banked blood, or direct patient-to-patient transfusion to lessen or eliminate the spread of disease.
Integration with extracorporeal blood circuits in clinical procedures, including dialysis, cardiopulmonary bypass, hemofiltration, blood oxygenation, and related therapies.
Use in a continuous loop with a part of the patient's bloodstream for ongoing treatment.
Removal of heparin-binding viruses, bacteria, and parasites from blood, such as adenovirus, coronavirus, HIV, Staphylococcus aureus, MRSA, Giardia lambitia, and others.
Selective removal of specific blood components, such as TNF-α, IL-6, IL-8, RANTES, and others, for immune modulation or organ preservation.
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