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-8409126-B2
Publication Date
2013-04-02
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 preventing inflammatory conditions by extracorporeally sequestering leukocytes and platelets from a subject and inhibiting their inflammatory activity. By temporarily adhering these cells to surfaces within a device, such as the exterior of hollow fibers, and exposing them to an agent like a calcium chelator (e.g., citrate), the invention inhibits the cells' release of pro-inflammatory substances or deactivates the cells.
This invention addresses the significant clinical problem of inflammation-related diseases, such as systemic inflammatory response syndrome (SIRS), sepsis, and complications following medical procedures like cardiopulmonary bypass, where activated leukocytes and platelets play a critical role in causing tissue injury and multi-organ dysfunction. Traditional therapies, including antibiotics and fluid management, may be inadequate or have significant drawbacks, driving the need for novel, effective interventions.
Within the described systems, a device defines a passageway or region that sequesters primed or activated leukocytes and/or platelets using features such as membranes or controlled shear forces, and applies an agent capable of inhibiting their inflammatory action. Devices may incorporate features such as porous or non-porous membranes, and adjustable flow rates to ensure effective sequestration and exposure to the deactivating agent. After treatment, the modified cells can be returned to the subject.
Claims Coverage
The patent claims cover two core inventive features relating to methods for extracorporeal processing and sequestration of primed or activated leukocytes using a calcium chelator, particularly for subjects with acute renal failure.
Extracorporeal sequestration and treatment of primed or activated leukocytes with a calcium chelator
The claimed method involves: - **Sequestering extracorporeally** the primed or activated leukocytes from a subject's body fluid using a device configured with a passageway or region for sequestration, such as a membrane (which may be porous and have a large surface area), and with specific conditions controlling shear force to enhance binding (e.g., less than about 1000 or 100 dynes/cm² with flow rates from about 100 mL/min to about 500 mL/min). - **Treating the sequestered leukocytes** during this process with a calcium chelator (such as citrate) to inhibit the release of pro-inflammatory substances from the cells or to deactivate the cells. The method specifies that exposure time to the chelator can range from less than an hour up to 24 hours. - The method is explicitly directed to subjects with acute renal failure. - The claims also contemplate returning the processed cells to the subject after treatment.
Method of treating a subject with acute renal failure by sequestration and deactivation of leukocytes using a calcium chelator
This inventive feature covers: - **Treating a subject with acute renal failure** by extracorporeally sequestering primed or activated leukocytes from the subject's body fluid. - **Treating the sequestered leukocytes** with a calcium chelator (such as citrate) to inhibit release of pro-inflammatory substances or deactivate the leukocytes, thereby ameliorating inflammation or inflammatory response associated with these cells. - Specifies that the sequestration is for a sufficient or prolonged period (e.g., at least one hour), possibly using a membrane within a device, and that the calcium chelator is infused into the passageway or region of sequestration. - Includes returning the treated leukocytes to the subject after processing.
The claims define methods and systems for extracorporeal sequestration and chemical deactivation of leukocytes in subjects with acute renal failure by employing a device to sequester the cells and applying a calcium chelator to inhibit their pro-inflammatory action before optional reinfusion.
Stated Advantages
Provides unprecedented and surprising success in maximizing subject survival across a range of inflammatory diseases and conditions.
Effectively ameliorates multi-organ effects of inflammatory conditions, such as sepsis and SIRS, by inhibiting leukocyte inflammatory activity.
Reduces inflammatory injury by sequestering and deactivating activated leukocytes and platelets before returning them to the subject.
Demonstrated to improve cardiovascular parameters, maintain renal blood flow, and increase survival rates in acute inflammatory models.
Demonstrates a marked improvement over traditional therapies, such as heparin anticoagulation, in animal and human studies.
Offers the ability to customize treatment circuits—single or multiple device systems and integration with existing extracorporeal circuits.
Documented Applications
Treatment and/or prevention of inflammatory conditions including systemic inflammatory response syndrome (SIRS), sepsis, cardiopulmonary bypass syndrome, acute respiratory distress syndrome (ARDS), rheumatoid arthritis, systemic lupus erythematosis, inflammatory bowel disease, multiple sclerosis, psoriasis, allograft rejection, asthma, chronic renal failure, cardiorenal syndrome, hepatorenal syndrome, and acute organ failure from ischemic reperfusion injury or toxic injury.
Treatment of inflammatory complications during or after medical interventions, including cardiopulmonary bypass and dialysis procedures.
Therapeutic intervention to ameliorate acute renal failure and related multiorgan dysfunctions.
Support for ex vivo tissue and organ development, organ harvesting procedures for transplantation, tissue engineering, and manufacture/use of bio-micro electromechanical systems (MEMs).
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