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-8430832-B2
Publication Date
2013-04-30
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 extracorporeally sequestering leukocytes and/or platelets and inhibiting their inflammatory activity. The systems utilize a device—specifically, a selective cytopheresis inhibitory device (SCID)—which allows the activated or primed leukocytes or platelets in a biological sample, such as blood, to associate with internal surfaces of the device. An agent, preferably a calcium chelating agent such as citrate, is provided to deactivate the sequestered cells or inhibit release of pro-inflammatory substances.
A main problem addressed is that numerous inflammatory conditions, including systemic inflammatory response syndrome (SIRS), sepsis, ischemia/reperfusion injury, and organ failure, are exacerbated by unwanted activation of immune cells, particularly leukocytes and platelets. Existing treatments, such as antibiotics and fluid therapy, as well as pharmaceutical anti-inflammatory agents, may be ineffective, costly, or even contraindicated in certain cases. Furthermore, medical interventions like cardiopulmonary bypass can induce profound activation of these inflammatory cells, resulting in tissue injury and high mortality rates.
The innovation lies in the extracorporeal manipulation of blood or other fluids by capturing and treating inflammatory cells to reduce their pathological action before returning them to the subject. The SCID's design reduces cell activation during flow by employing a low-shear environment and optionally utilizes membranes or surfaces that facilitate cell adhesion. Treatment with an inhibitor, such as citrate, in situ effectively reduces the risk or severity of inflammation-associated tissue damage. This method aims to directly treat or prevent both acute and chronic inflammatory diseases through this cell-targeted approach.
Claims Coverage
There are two independent claims in this patent, each outlining key inventive features regarding the sequestration and treatment of leukocytes with a calcium chelating agent for inflammatory control.
Extracorporeal sequestration and treatment of primed or activated leukocytes with a calcium chelating agent
The method involves: - Sequestering primed or activated leukocytes extracorporeally from a subject with end-stage renal disease. - Treating the sequestered leukocytes with a calcium chelating agent to inhibit the release of a pro-inflammatory substance or to deactivate the leukocytes. Additional features include: - Sequestration in a device defining a passageway with a region configured to retain the cells. - Use of membranes (optionally porous, with surface area greater than 0.2 m2) as the sequestration surface. - The calcium chelating agent is preferably citrate and may be infused into the passageway. - The region is configured for low shear force (<1000 dynes/cm2) during flow rates of about 100–500 mL/minute, enabling effective cell sequestration.
Treatment of inflammation in end-stage renal disease by extracorporeal sequestration and chemical modulation of leukocytes
This method comprises: - Sequestering primed or activated leukocytes extracorporeally from a subject's body fluid. - Treating the sequestered leukocytes with a calcium chelating agent (preferably citrate) to inhibit release of pro-inflammatory substances or deactivate the leukocytes or platelets. The process also encompasses: - Performing the sequestration in a device with a defined passageway and a membrane-based region for capturing leukocytes. - Ensuring the sequestration region operates at shear forces less than 1000 dynes/cm2 with fluid flow rates between 100–500 mL/minute. - Providing the option of returning the treated leukocytes back to the subject.
The claims protect methods for extracorporeal sequestration of primed or activated leukocytes (and optionally platelets) and their treatment with a calcium chelating agent, specifically detailing device configurations for cell retention, agent delivery, and treatment conditions optimizing inhibition of inflammatory activity.
Stated Advantages
The systems, devices, and methods maximize subject survival by reducing multi-organ effects of inflammatory diseases such as sepsis and SIRS.
They enable effective sequestration and deactivation or inhibition of inflammatory activity of leukocytes and platelets.
Treatment leads to amelioration of the inflammatory state of sequestered cells, reducing the risk or severity of inflammation-associated tissue damage.
These systems can be applied to a wide range of acute and chronic inflammatory conditions, illustrating broad utility.
Use of a calcium chelating agent, such as citrate, in the device improves the innate immunologic system of the subject.
Device design using low shear force surfaces allows for efficient sequestration of targeted cells while minimizing undesired activation.
Documented Applications
Treatment or prevention of systemic inflammatory response syndrome (SIRS), sepsis, ischemia/reperfusion injury, and acute respiratory distress syndrome (ARDS).
Treatment of chronic conditions such as end stage renal disease (ESRD), chronic renal failure, rheumatoid arthritis, systemic lupus erythematosis, inflammatory bowel disease, multiple sclerosis, and psoriasis.
Use in managing inflammatory complications following cardiovascular surgery, including cardiopulmonary bypass-induced acute lung injury (ALI) and acute kidney injury (AKI).
Application during medical interventions that induce inflammatory responses, such as dialysis, hemofiltration, or cardiopulmonary bypass surgery.
Support for organ harvesting procedures for transplantation, tissue engineering applications, ex vivo generation of organs, and manufacture or use of bio-micro electromechanical systems (MEMs).
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