Selective cytopheresis devices and related methods thereof
Inventors
Humes, H. David • Buffington, Deborah
Assignees
University of Michigan Ann Arbor • Seastar Medical Inc
Publication Number
US-9341626-B2
Publication Date
2016-05-17
Expiration Date
2028-08-29
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Abstract
The present invention relates to systems and devices to treat and/or prevent inflammatory conditions within a subject and to related methods. More particularly, the invention relates to systems, devices, and related methods that sequester leukocytes and/or platelets and then inhibit their inflammatory action.
Core Innovation
The invention provides systems, devices, and methods for treating and/or preventing inflammatory conditions within a subject by extracorporeal sequestration of cells associated with inflammation, such as leukocytes and platelets, and inhibiting their inflammatory activity. This is accomplished by sequestering activated or primed leukocytes and/or platelets in a device and treating them with an agent to inhibit the release of pro-inflammatory substances or to deactivate them, after which the treated blood is returned to the subject.
A primary approach employs a device containing hollow fibers, where blood passes along the exterior of these fibers under conditions of low shear force, allowing the activated leukocytes and/or platelets to adhere to the fiber surfaces. An agent, preferably a calcium chelating agent such as citrate, is provided to inhibit the release of pro-inflammatory substances from these cells and/or to deactivate them. The device is designed so that the exterior fiber surface area ranges from about 0.2 m2 to about 2.0 m2, and blood flow along the fibers maintains a shear force of less than 10 dynes/cm2.
The invention addresses the problem that current therapies for inflammatory conditions such as SIRS, sepsis, and related disorders are insufficient, often relying on broad-spectrum antibiotics, fluid therapy, and expensive or risky molecular agents. There remains an unmet need for an effective treatment that targets the inflammatory activity of leukocytes and platelets, which are central to many acute and chronic inflammatory pathologies.
Claims Coverage
The patent claims cover one independent inventive feature embodied in an extracorporeal device for treating inflammation in a subject, as described in claim 1.
Extracorporeal device with hollow fibers for selective sequestration and deactivation of inflammatory cells
The device comprises: - A housing with a fluid inlet to receive blood from a subject and a fluid outlet to return the blood after treatment. - Plurality of parallel hollow fibers within the housing, each with an intracapillary space (interior) and an exterior surface. The first ends of the hollow fibers are capped so that fluid cannot enter the interiors during operation. - The exterior surfaces of the hollow fibers, together providing a surface area from about 0.2 m2 to about 2.0 m2, are configured for binding activated leukocytes and/or activated platelets from the blood. - The device permits blood, after entering from the fluid inlet, to pass along the exterior surfaces of the hollow fibers from inlet to outlet, allowing sequestration of inflammatory cells under a shear force of less than 10 dynes/cm2 at fluid flow rates from about 100 mL/minute to about 500 mL/minute. - The housing is configured to preclude attachment of a tube in fluid communication with the first ends of the fibers during operation. Additional features in dependent claims include: - Caps preventing fluid access at both ends of the hollow fibers. - Locking connectors for blood line attachment. - Systems for infusing citrate into the blood entering the device and for infusing calcium into the blood leaving the device.
The patent claims cover a device focused on extracorporeal binding and inhibition of inflammatory action from leukocytes and platelets using hollow fibers, specific flow dynamics, and configuration to maximize efficacy and safety in the treatment of inflammatory conditions.
Stated Advantages
The system and methods effectively treat or prevent a variety of inflammatory conditions by directly deactivating or inhibiting pro-inflammatory activity of leukocytes or platelets in blood before returning it to the subject.
Addition of a calcium chelator such as citrate, combined with the sequestration device, results in unprecedented and surprising improvements in subject survival and amelioration of the inflammatory state.
The device can successfully maximize subject survival across a range of inflammatory diseases and conditions, including those where standard treatments are ineffective.
The configuration allows for selective sequestration and deactivation of activated or primed leukocytes and/or activated platelets, minimizing multi-organ effects of inflammatory responses.
The device achieves sequestration of inflammatory cells without the need for additional cell-based therapies within the cartridge.
Documented Applications
Treatment and/or prevention of systemic inflammatory response syndrome (SIRS), sepsis, cardiopulmonary bypass syndrome, acute respiratory distress syndrome (ARDS), and related acute inflammatory conditions.
Therapy for chronic inflammatory states such as end stage renal disease (ESRD).
Reduction of organ dysfunction and failure arising from trauma, infection, ischemia/reperfusion injury, burns, and major surgical procedures.
Application within extracorporeal circuits such as hemofiltration, hemodialysis, or cardiopulmonary bypass systems for inflammatory cell sequestration and deactivation.
Support for organ harvesting procedures, tissue engineering applications, ex vivo organ generation, and use in bio-microelectromechanical systems (MEMs).
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