IP Library Granted Patent US 10,667,510
Granted Patent B2
US 10,667,510 · App. 15/066,672 · Granted Jun 2, 2020

Administration and monitoring of nitric oxide in ex vivo fluids

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Quick Facts
Patent No.
US 10,667,510
App. No.
15/066,672
Granted
Jun 2, 2020
Kind
B2
Abstract

Described are systems and methods for monitoring administration of nitric oxide (NO) to ex vivo fluids. Examples of such fluids include blood in extracorporeal membrane oxygenation (ECMO) circuits or perfusion fluids used for preserving ex vivo organs prior to transplanting in a recipient. The systems and methods described herein provide for administering nitric oxide to the fluid, monitoring nitric oxide or a nitric oxide marker in the fluid, and adjusting the nitric oxide administration.

Claims (42)

1. A method of perfusion, the method comprising:

perfusing a lung with a perfusion fluid;

monitoring methemoglobin in the perfusion fluid; and

adjusting an amount of NO or NO donor provided to the lung according to the methemoglobin monitored.

2. The method of claim 1 wherein the perfusion fluid includes NO or an NO donor.

3. The method of claim 2 , further comprising:

monitoring at least one additional parameter of the perfusion fluid including at least one of NO, a NO marker and an indicator of tissue damage; and

adjusting the amount of NO or NO donor provided to the lung according to the methemoglobin and the additional parameter monitored.

4. The method of claim 3 wherein the perfusion fluid includes red blood cells.

5. The method of claim 1 wherein the lung is perfused and ventilated simultaneously.

6. The method of claim 1 wherein the lung is perfused and persufflated simultaneously.

7. The method of claim 6 wherein the perfusion fluid has a first composition and a preservation fluid having a second composition is used to store the lung during persufflation.

8. The method of claim 1 wherein the monitoring is continuous.

9. A method of preserving a lung, comprising:

perfusing an ex vivo lung with a perfusion fluid including NO or an NO donor;

continuously monitoring methemoglobin;

and

in response to the methemoglobin being monitored, adjusting an amount of NO or NO donor provided to the lung to maintain NO dosing to the lung within a desired range.

10. The method of claim 9 further comprising monitoring at least one additional parameter of the perfusion fluid including at least one of NO, a NO marker and an indicator of tissue damage.

11. The method of claim 9 wherein the step of monitoring is accomplished by a monitoring device that is part of or integrated with a NO delivery device.

12. The method of claim 9 wherein the perfusion fluid includes at least one of a histidine-tryptophan-ketoglutarate solution and a colloid-containing, extracellular-type low K+electrolyte solution.

13. The method of claim 9 , further comprising:

monitoring at least one secondary parameter including at least one of pulmonary vascular resistance (PVR), pulmonary capillary wedge pressure (PCWP) and mean pulmonary arterial pressure (mPAP); and

adjusting the amount of NO or NO donor provided to the lung according to the monitored secondary parameter.

14. The method of claim 13 wherein the perfusion fluid includes red blood cells.

15. The method of claim 13 wherein the perfusion fluid has a first composition and a preservation fluid having a second composition is used to store the lung during persufflation.

16. A method of preserving a lung for transplant, comprising:

perfusing an ex vivo lung with a perfusion fluid, wherein the perfusion fluid is circulated through a perfusion circuit;

wherein the perfusion fluid includes one of NO or an NO donor provided from a NO source;

continuously monitoring at least one parameter of the perfusion fluid;

wherein the parameter includes a NO marker; and

in response to the parameters being monitored, adjusting an amount of NO or NO donor provided to the lung to avoid at least one of overdosing and underdosing the lung.

17. The method of claim 16 further comprising the steps of:

after perfusion of the lung has begun, persufflating the lung with a persuffation gas.

18. The method of claim 16 , further comprising the steps of:

terminating NO administration to the lung;

flushing the lung in anticipation of implantation.

19. The method of claim 16 , further comprising the steps of:

purging a portion of the perfusion fluid that is circulated through the perfusion circuit.

20. The method of claim 19 , further comprising the steps of:

replacing the purged perfusion fluid with additional perfusion fluid; and

adjusting the amount of NO or NO donor provided to the lung to compensate for the NO content removed by the purging of perfusion fluid.

Assignments (18)
SECURITY INTEREST Recorded Oct 28, 2025
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To: GOLDMAN SACHS BANK USA, AS ADMINISTRATIVE AGENT
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SECURITY INTEREST Recorded Aug 1, 2025
From: MALLINCKRODT PHARMACEUTICALS IRELAND LIMITED
To: COMPUTERSHARE TRUST COMPANY, NATIONAL ASSOCIATION
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RELEASE OF PATENT SECURITY INTERESTS RECORDED AT REEL 060434, FRAME 0536 Recorded Nov 16, 2023
From: DEUTSCHE BANK AG NEW YORK BRANCH, AS COLLATERAL AGENT
To: MALLINCKRODT ENTERPRISES LLC; MALLINCKRODT LLC; SPECGX LLC; OCERA THERAPEUTICS, INC.; STRATATECH CORPORATION; VTESSE LLC; MALLINCKRODT PHARMA IP TRADING UNLIMITED COMPANY; MALLINCKRODT PHARMACEUTICALS IRELAND LIMITED; SUCAMPO PHARMA AMERICAS LLC
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RELEASE OF PATENT SECURITY INTERESTS RECORDED AT REEL 043601, FRAME 0025 Recorded Nov 16, 2023
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To: MALLINCKRODT INTERNATIONAL FINANCE S.A.; MALLINCKRODT CB LLC; MALLINCKRODT FINANCE GMBH; MALLINCKRODT US HOLDINGS LLC (F/K/A MALLINCKRODT US HOLDINGS INC.); MALLINCKRODT CARRIBEAN, INC.; MALLINCKRODT US POOL LLC; MNK 2011 LLC (F/K/A MALLINCKRODT INC.); LUDLOW LLC (F/K/A LUDLOW CORPORATION); CNS THERAPEUTICS, INC.; MALLINCKRODT ENTERPRISES HOLDINGS LLC (F/K/A MALLINCKRODT ENTERPRISES HOLDINGS, INC.); MALLINCKRODT ENTERPRISES LLC; MALLINCKRODT LLC; LAFAYETTE PHARMACEUTICALS LLC; LIEBEL-FLARSHEIM COMPANY LLC; MALLINCKRODT BRAND PHARMACEUTICALS LLC (F/K/A MALLINCKRODT BRAND PHARMACEUTICALS, INC.); MALLINCKRODT VETERINARY, INC.; MALLINCKRODT US HOLDINGS LLC; IMC EXPLORATION COMPANY; MEH, INC.; MALLINCKRODT HOSPITAL PRODUCTS IP UNLIMITED COMPANY (F/K/A MALLINCKRODT HOSPITAL PRODUCTS IP LIMITED); MALLINCKRODT ARD IP UNLIMITED COMPANY (F/K/A MALLINCKRODT ARD IP LIMITED); OCERA THERAPEUTICS LLC (F/K/A OCERA THERAPEUTICS, INC.); SPECGX LLC; STRATATECH CORPORATION; SUCAMPO PHARMA AMERICAS LLC; VTESSE LLC (F/K/A VTESSE INC.); MALLINCKRODT PHARMACEUTICALS IRELAND LIMITED; MALLINCKRODT PHARMA IP TRADING UNLIMITED COMPANY (F/K/A MALLINCKRODT PHARMA IP TRADING D.A.C.); INFACARE PHARMACEUTICAL CORPORATION; ST SHARED SERVICES LLC; THERAKOS, INC.; IKARIA THERAPEUTICS LLC; INO THERAPEUTICS LLC
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From: MALLINCKRODT ENTERPRISES LLC; MALLINCKRODT LLC; MALLINCKRODT PHARMA IP TRADING UNLIMITED COMPANY; MALLINCKRODT PHARMACEUTICALS IRELAND LIMITED; OCERA THERAPEUTICS LLC; SPECGX LLC; STRATATECH CORPORATION; SUCAMPO PHARMA AMERICAS LLC; VTESSE LLC
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To: DEUTSCHE BANK AG NEW YORK BRANCH
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To: WILMINGTON SAVINGS FUND SOCIETY, FSB, AS SECOND LIEN COLLATERAL AGENT
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RELEASE OF SECURITY INTEREST Recorded Jun 17, 2022
From: WILMINGTON SAVINGS FUND SOCIETY, FSB, AS SECOND LIEN COLLATERAL AGENT
To: OCERA THERAPEUTICS, INC.; MALLINCKRODT LLC; MALLINCKRODT ARD IP UNLIMITED COMPANY (F/K/A MALLINCKRODT ARD IP LIMITED); MALLINCKRODT HOSPITAL PRODUCTS IP UNLIMITED COMPANY (F/K/A MALLINCKRODT HOSPITAL PRODUCTS IP LIMITED); MALLINCKRODT PHARMA IP TRADING UNLIMITED COMPANY (F/K/A MALLINCKRODT PHARMA IP TRADING DESIGNATED ACTIVITY COMPANY); SPECGX LLC; STRATATECH CORPORATION; VTESSE LLC (F/K/A VTESSE INC.)
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From: POTENZIANO, JIM; HANSELL, DOUGLAS R.; GRIEBEL, JEFF; COSTA, EDWARD, JR.; COOPER, LISA
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