Selective cytopheresis devices and related methods
Inventors
Humes, H. David • Buffington, Deborah
Assignees
University of Michigan Ann Arbor • Seastar Medical Inc
Publication Number
US-8425446-B2
Publication Date
2013-04-23
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 by extracorporeally sequestering leukocytes and/or platelets and inhibiting their inflammatory actions. The core of the invention involves collecting cells associated with inflammation, such as activated or primed leukocytes, exposing them to an agent—preferably a calcium chelating agent like citrate—to either deactivate the cells or inhibit the release of pro-inflammatory substances, and then returning the processed cells or blood to the subject.
The problem being solved is that various medical conditions (including infections, trauma, cardiovascular events, and endogenous inflammatory reactions) lead to unwanted or uncontrolled inflammation. This uncontrolled activation of immune cells such as leukocytes and platelets contributes to organ dysfunction, microvascular injury, and may result in life-threatening or fatal outcomes. Current therapies (such as antibiotics, fluids, and anti-inflammatory agents) are often insufficient, expensive, or have adverse side effects. There is thus a need for an effective, targeted treatment for inflammatory conditions like sepsis, SIRS, and related syndromes.
The devices, termed selective cytopheresis inhibitory devices (SCIDs), are designed to sequester these inflammatory cells on specific surfaces (such as the exterior of hollow fibers) within a passageway of the device, under conditions of low shear force to facilitate cell association. These cells are then treated with a leukocyte inhibiting agent, most notably calcium chelators like citrate, which deactivates the cells and/or inhibits the release of pro-inflammatory substances. The invention can be used as a standalone device or as part of a system, potentially in combination with other blood treatment devices. The methods address both acute and chronic inflammatory conditions.
Claims Coverage
The patent contains two independent claims, each focusing on core inventive features related to extracorporeal sequestration and treatment of activated leukocytes with a calcium chelator.
Extracorporeal sequestration and calcium chelator treatment of primed or activated leukocytes
A method for processing cells contained within a body fluid from a subject with sepsis, where: - Primed or activated leukocytes are extracorporeally sequestered from the subject. - The sequestered cells are treated during sequestration with a calcium chelator to inhibit the release of a pro-inflammatory substance or to deactivate the cells. - The method may comprise returning the treated cells to the subject. - The calcium chelator may comprise citrate. - The sequestration may occur over a sufficient or prolonged period, including at least one hour or from 1 to 24 hours. - The sequestration uses a device defining a passageway with a region configured to sequester the cells, potentially a membrane (which may be porous and have a surface area >0.2 m²) and configured for low shear force (<1000 dynes/cm² or <100 dynes/cm² at specified flow rates). - The calcium chelator may be infused into the passageway.
Treatment of sepsis by extracorporeal sequestration and calcium chelator treatment of leukocytes
A method for treating a subject with sepsis, where: - Primed or activated leukocytes in a body fluid from the subject are extracorporeally sequestered. - The leukocytes sequestered during sequestration are treated with a calcium chelator to inhibit release of a pro-inflammatory substance or to deactivate the leukocytes. - The calcium chelator may ameliorate an inflammatory response, and includes citrate. - The method includes aspects such as sufficient or prolonged sequestration time (including at least one hour or from 1 to 24 hours), possibly returning treated leukocytes to the subject, use of devices as described for sequestration, membrane characteristics, and low shear force regions. - The calcium chelator can be infused into the device's passageway.
The independent claims broadly cover methods for extracorporeally sequestering primed/activated leukocytes from a subject with sepsis, treating them during sequestration with a calcium chelator (including citrate), and structural features of the device (passageway, membrane, low shear force) to facilitate sequestration and inhibition of inflammatory activity.
Stated Advantages
The systems, devices, and methods provide unprecedented and surprising success in maximizing subject and patient survival across a range of inflammatory diseases and conditions.
The invention effectively ameliorates the multi-organ effects of inflammatory diseases such as sepsis and SIRS, including improving cardiac output, renal blood flow, and reducing mortality rates.
Treatment with these devices shows compelling utility for both acute and chronic pro-inflammatory conditions, such as end stage renal disease, by targeting activated and/or primed leukocytes and platelets.
The selective cytopheresis approach enables direct treatment of a subject's blood to deactivate or inhibit inflammatory cells, potentially addressing limitations of standard therapies like antibiotics and anti-inflammatory drugs.
The system allows use of single or multiple device configurations, offering flexibility in therapeutic interventions with simplified circuits when appropriate.
Documented Applications
Treatment and/or prevention of inflammatory conditions including systemic inflammatory response syndrome (SIRS), cardiopulmonary bypass syndrome, acute respiratory distress syndrome (ARDS), sepsis, rheumatoid arthritis, systemic lupus erythematosis, inflammatory bowel disease, multiple sclerosis, psoriasis, allograft rejection, asthma, chronic renal failure, cardiorenal syndrome, hepatorenal syndrome, acute organ failure from ischemic reperfusion injury, and acute organ failure due to toxic injury.
Use as part of extracorporeal circuits for treatment during cardiopulmonary bypass procedures to reduce organ dysfunction and inflammatory complications.
Application for treating inflammation associated with acute renal failure in human subjects, specifically for improving survival in patients with multiple organ failure receiving continuous hemofiltration.
Treatment of chronic inflammatory states in end stage renal disease (ESRD) patients undergoing dialysis, aiming to reduce mortality and improve clinical outcomes.
Use in research, diagnostic applications, and support of the development and use of tissues and organs ex vivo, including organ harvesting for transplantation and tissue engineering.
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