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-8425447-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 present invention provides systems, devices, and methods for treating and/or preventing inflammatory conditions in a subject by extracorporeally sequestering cells associated with inflammation, such as leukocytes and platelets, and then inhibiting or deactivating their inflammatory action. The invention permits sequestration of activated or primed leukocytes or platelets in a defined region within a device, for example, by associating with the surface of hollow fibers, and then exposing these cells to an agent capable of inhibiting the release of pro-inflammatory substances or deactivating them.
A primary problem being addressed is the lack of effective treatments for inflammatory conditions such as sepsis, systemic inflammatory response syndrome (SIRS), and complications arising from trauma, infection, or surgical procedures like cardiopulmonary bypass. Existing therapies, such as broad-spectrum antibiotics, fluid therapy, and certain drugs, do not adequately manage the excessive immune response and may not prevent multi-organ failure or death due to unchecked leukocyte and platelet activation.
The systems and devices of the invention achieve selective cytopheresis by providing a passageway or region configured to bind and sequester the target cells from a biological fluid, most commonly blood, and then expose these cells to agents such as calcium chelators, preferably citrate, to inhibit the release of pro-inflammatory substances or deactivate the cells. The device configurations ensure sufficiently low shear force to allow for prolonged association of the leukocytes with the sequestration surfaces, maximizing the anti-inflammatory effect before the cells or their contents are returned to the subject.
Claims Coverage
The independent claim defines one main inventive feature in the patent relating to a system for treating primed or activated leukocytes with specific structural and functional characteristics.
System for extracorporeal sequestration and inhibition/deactivation of inflammatory leukocytes
A system intended for treating primed or activated leukocytes from a subject, comprising: - A device with a passageway that allows body fluid (such as blood) from the subject to pass through. - Within the passageway, a region is specifically configured to bind (sequester) primed or activated leukocytes present in the fluid. - Inclusion of a calcium chelating agent capable of inhibiting the release of a pro-inflammatory substance from the primed or activated leukocytes or deactivating those leukocytes. The system further covers: - The use of specific calcium chelating agents such as citrate, sodium hexametaphosphate, EDTA, triethylene tetramine, diethylene triamine, o-phenanthroline, or oxalic acid. - The region configured for sequestration may include a membrane (porous or otherwise), may be defined by or include the surface of fibers (including hollow fibers) within a housing, and is designed to have controlled shear force (less than about 1000 dynes/cm2 at 100–500 mL/min flow rates) to facilitate leukocyte binding. - The system can be used for subjects experiencing various inflammatory conditions as specifically exemplified in the claims, such as SIRS, cardiopulmonary bypass syndrome, ARDS, sepsis, rheumatoid arthritis, systemic lupus erythematosis, inflammatory bowel disease, multiple sclerosis, psoriasis, allograft rejection, asthma, acute renal failure, chronic renal failure, cardiorenal syndrome, hepatorenal syndrome, acute organ failures, and conditions associated with end-stage renal disease or cardiopulmonary bypass. - The device may be cell-free and configured to bind leukocytes for a time sufficient for inhibition or deactivation to occur.
The claim coverage is focused on a system utilizing a device and a calcium chelating agent to selectively bind and deactivate or inhibit inflammatory leukocytes (and, in general, other cells associated with inflammation), with defined structural characteristics of the sequestration region and detailed functional limitations, enabling treatment of a wide range of inflammatory conditions.
Stated Advantages
The invention maximizes subject survival across a range of inflammatory diseases and conditions.
It provides unprecedented and surprising success in treating sepsis, SIRS, and other acute and chronic inflammatory conditions.
The systems effectively sequester activated and/or primed leukocytes and platelets, and inhibit their inflammatory activity.
The addition of a calcium chelator, such as citrate, unexpectedly improves a subject's innate immunologic system.
The invention reduces multi-organ effects of inflammatory diseases, such as cardiac output and renal blood flow loss, and lowers inflammatory cytokines in animal and human models.
Device configurations can be integrated into existing treatments such as hemofiltration, hemodialysis, or cardiopulmonary bypass circuits with established safety features and protocols.
The systems and methods provide reduced activation and degranulation of leukocytes, resulting in less vascular and tissue damage.
Documented Applications
Treatment and/or prevention of inflammatory conditions in a subject, including SIRS, sepsis, ARDS, and multi-organ effects of acute or chronic inflammatory diseases.
Use in conjunction with hemofiltration, hemodialysis, or hemodiafiltration systems for extracorporeal blood treatment.
Integration into cardiopulmonary bypass (CPB) circuits for treating or preventing inflammation secondary to surgery, including post-pump syndrome, acute lung injury (ALI), and acute kidney injury (AKI).
Treatment of autoimmune disorders such as rheumatoid arthritis, systemic lupus erythematosis, inflammatory bowel disease, multiple sclerosis, psoriasis, and asthma.
Treatment of organ failure due to ischemic reperfusion injury to heart, central nervous system, liver, kidney, or pancreas, and organ failure due to toxic injury (e.g., chemotherapy).
Use in supporting development and use of tissues and organs ex vivo, including organ harvesting for transplantation, tissue engineering, and ex vivo organ generation.
Support of chronic inflammatory conditions such as end stage renal disease and cardiorenal or hepatorenal syndromes.
Use in treatment of inflammatory conditions associated with medical procedures (e.g., dialysis, surgical trauma).
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