Cartridge and method for increasing myocardial function
Inventors
Humes, H. David • Buffington, Deborah A. • Pino, Christopher J.
Assignees
Innovative Biotherapies Inc • Seastar Medical Inc
Publication Number
US-10695482-B2
Publication Date
2020-06-30
Expiration Date
2032-10-10
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Abstract
The present invention relates to a cytopheretic cartridge for use in treating and/or preventing inflammatory conditions that affect myocardial function and to related methods. The cartridge can be used in treating a subject with myocardial dysfunction, such as a subject with chronic heart failure and/or acute decompensated heart failure.
Core Innovation
The invention relates to methods and cytopheretic cartridges for treating and/or preventing inflammatory conditions that affect myocardial function. The approach centers on extracorporeally sequestering activated leukocytes and/or platelets from a subject's body fluid in a specialized cartridge, then inhibiting their inflammatory actions by deactivation or inhibition of pro-inflammatory substance release, especially through the application of agents such as calcium chelators.
This invention is designed to address the need for improved treatments for inflammatory conditions that cause or worsen myocardial dysfunction, such as chronic heart failure and acute decompensated heart failure. Existing therapies have limited efficacy and can lead to significant complications, including further declines in renal function or adverse cardiac events. The central problem is the uncontrolled activation of leukocytes and platelets, which drives damaging inflammation and contributes to microvascular injury and cardiac dysfunction.
The cytopheretic cartridge consists of a rigid housing with an inner volume, equipped with a solid support that presents a fluid contacting surface capable of sequestering activated leukocytes and platelets. The method involves introducing the subject’s body fluid into the cartridge, exposing these cells to agents—typically calcium chelators such as citrate—that inhibit inflammatory activity, and then returning the treated fluid and deactivated cells to the subject. This process aims to improve myocardial parameters such as ejection fraction, cardiac output, and vascular resistance while reducing the risk and progression of inflammation-driven heart dysfunction.
Claims Coverage
The patent contains two independent method claims, each emphasizing inventive features around extracorporeal sequestration of activated leukocytes and/or platelets in a specially configured cartridge, treatment with a calcium chelating agent, and return of the processed cells to the subject.
Extracorporeal sequestration in a cartridge with specific SA/IV ratio
A method involving: - Sequestration of activated leukocytes and/or platelets from a subject’s body fluid in a cartridge containing a rigid housing, fluid inlet/outlet ports, and a solid support. - The cartridge is defined by a surface area (SA) to inner volume (IV) ratio greater than 80 cm−1 or within the range 25 cm−1 to 2,000 cm−1, ensuring effective sequestration. - Body fluid is introduced and conditions permit binding of activated cells on the solid support's fluid contacting surface.
Treatment of sequestered leukocytes/platelets with a calcium chelating agent
- The method requires treating the leukocytes and/or platelets sequestered in the cartridge with a calcium chelating agent. - Treatment is designed to inhibit the release of pro-inflammatory substances or deactivate the leukocytes/platelets. - Calcium chelating agents may include citrate.
Return of treated leukocytes/platelets to the subject
- After treatment with the calcium chelating agent, the processed leukocytes and/or platelets are returned to the subject. - This step completes the extracorporeal therapy to treat or prevent chronic heart failure or related inflammatory myocardial conditions.
In summary, the inventive features cover a defined cartridge system for extracorporeal sequestration of activated leukocytes/platelets using specific surface area ratios, treatment of these cells with a calcium chelating agent to inhibit inflammatory action, and the return of these cells to the subject to address myocardial inflammatory conditions.
Stated Advantages
Improves myocardial function by increasing parameters such as left ventricular ejection fraction, cardiac output, and stroke volume in subjects with chronic heart failure or acute decompensated heart failure.
Reduces systemic inflammation by sequestering and deactivating activated leukocytes and/or platelets, thereby inhibiting release of pro-inflammatory substances.
Demonstrates enhanced survival time and protection against organ dysfunction in animal models of sepsis and chronic heart failure through combined use of the cartridge and calcium chelating agent.
Enables sustained improvement in cardiac parameters that can persist for hours or days after treatment termination.
Provides a means for selectively targeting inflammatory cells without causing clinically significant leukopenia or thrombocytopenia by using a controlled cartridge design.
Documented Applications
Treating subjects with chronic heart failure or acute decompensated heart failure by improving myocardial function and controlling inflammation.
Therapeutic or prophylactic treatment for subjects experiencing or at risk of organ or tissue rejection following transplantation (such as heart, liver, or kidney).
Preventing or treating inflammatory myocardial conditions linked to inflammatory cell migration into heart tissue.
Increasing myocardial function in subjects with chronic inflammation-related organ dysfunction, including use in conjunction with procedures such as cardiopulmonary bypass or continuous hemofiltration.
Use in the treatment of acute inflammatory conditions like sepsis to stabilize cardiovascular and renal function.
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