Selective cytopheresis devices and related methods thereof
View Patent ↗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.
1. A system for treating primed or activated leukocytes from a subject in need thereof, the system comprising:
a device defining a passageway that permits body fluid from the subject to pass therethrough, the passageway comprising a region configured to bind the primed or activated leukocytes; and
a calcium chelating agent capable of inhibiting release of a pro-inflammatory substance from the primed or activated leukocytes or deactivating the primed or activated leukocytes.
2. The system of claim 1 , further comprising a second device in series with the device defining the passageway.
3. The system of claim 1 , wherein the agent is associated with a surface of the passageway.
4. The system of claim 1 , wherein the agent is infused into the passageway.
5. The system of claim 1 , wherein the calcium chelating agent comprises citrate.
6. The system of claim 1 , wherein the calcium chelating agent is one or more of citrate, sodium hexametaphosphate, ethylene diamine tetra-acetic acid (EDTA), triethylene tetramine, diethylene triamine, o-phenanthroline, and oxalic acid.
7. The system of claim 1 , wherein the region configured to bind the leukocytes comprises a membrane.
8. The system of claim 7 , wherein the membrane is porous.
9. The system of claim 7 , wherein the membrane has a surface area greater than about 0.2 m 2 .
10. The system of claim 7 , wherein the membrane permits the passage of fluid therethrough.
11. The system of claim 7 , wherein the surface of the membrane binds the leukocytes.
12. The system of claim 1 , wherein the region configured to bind the leukocytes is configured such that shear force within the region is less than about 1000 dynes/cm 2 when fluid passes through the passageway at a rate of from about 100 mL/minute to about 500 mL/minute.
13. The system of claim 12 , wherein the region configured to bind leukocytes is configured such that shear force within the region is less than about 100 dynes/cm 2 when fluid passes through the passageway at a rate of from about 100 mL/minute.
14. The system of claim 1 , wherein the region configured to bind the leukocytes comprises a cell-adhesion molecule.
15. The system of claim 1 , wherein the region is defined by the surface of a fiber or plurality of fibers.
16. The system of claim 15 , wherein the device comprises a housing and a fiber or a plurality of fibers disposed therein, wherein each fiber has an exterior surface that binds the leukocytes.
17. The system of claim 16 , wherein the passageway is formed by the space surrounding the fiber or fibers within the housing.
18. The system of claim 16 , wherein the exterior surface of the fiber binds the leukocytes.
19. The system of claim 15 , wherein the fiber is, or plurality of fibers are, hollow.
20. The system of claim 1 , wherein the subject has an inflammatory condition selected from the group consisting of 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; acute renal failure; chronic renal failure; cardiorenal syndrome; hepatorenal syndrome; acute organ failure from ischemic reperfusion injury to myocardium, central nervous system, liver, kidney, or pancreas; and an inflammatory condition associated with end-stage renal disease or a cardiopulmonary-bypass procedure.
21. The system of claim 1 , wherein the subject has sepsis.
22. The system of claim 1 , wherein the subject has acute renal failure or end-stage renal disease.
23. The system of claim 1 , wherein the subject has an inflammatory condition associated with a cardio-pulmonary bypass procedure.
24. The system of claim 1 , wherein the device has an outlet configured to return leukocytes to the subject.
25. The system of claim 1 , wherein the device is cell-free.
26. The system of claim 1 , wherein the device is configured to bind the leukocytes for a time sufficient to permit the subsequent inhibition or release of a pro-inflammatory substance from the leukocytes and/or deactivation of the leukocytes.
27. The system of claim 1 , wherein a surface of the passageway binds the leukocytes.