IP Library Granted Patent US 8,790,715
Granted Patent B2
US 8,790,715 · App. 11/355,670 · Granted Jul 29, 2014

Method and apparatus for generating nitric oxide for medical use

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Quick Facts
Patent No.
US 8,790,715
App. No.
11/355,670
Granted
Jul 29, 2014
Kind
B2
Abstract

A method and system for generating and delivering nitric oxide directly to a patient. A reaction chamber is provided that is located at or in close proximity to the patient and reactants within the reaction chamber react together to produce a predetermined amount of nitric oxide. The reaction is controlled by metering at least one of the reactants into the reaction chamber to generate a predetermined quantity of nitric oxide as required by the patient. The reactants can include a nitrite salt, such as sodium nitrite, and a reductant such as ascorbic acid, maleic acid or a mixture thereof. By generating and delivering the nitric oxide directly to the patient in close proximity thereto, the formation of NO 2 is minimized. One or both of the reactants may be in liquid form.

Claims (32)

1. A method of controlled delivery of nitric oxide (NO) to the lung of a human patient in need thereof by inhalation comprising:

generating NO by reacting a nitrite salt and a reductant, wherein the nitrite salt is dissolved in aqueous droplets and the reductant is a solid disposed on a rotatable reaction surface;

controlling the amount of NO delivered to the lung of the patient by delivering the aqueous droplets of nitrite salt via pulses to the reductant on a first position on the rotatable reaction surface;

rotating the rotatable reaction surface to a second position; and

delivering the aqueous droplets of nitrite salt via pulses to the reductant on the second position on the rotatable reaction surface.

2. The method of claim 1 , wherein the NO is delivered at a concentration in the range of 5 ppm to 80 ppm.

3. The method of claim 2 , wherein the nitrite salt is sodium nitrite, and, wherein the reductant comprises ascorbic acid, maleic acid or a mixture thereof.

4. The method of claim 2 , wherein the reaction surface is a disc or tape.

5. The method of claim 3 , wherein the lung has an alveolar volume in the range of 300 mL to 400 mL at rest.

6. The method of claim 1 , wherein the reaction surface is adapted to be in movement causing the liquid droplets to contact the solid at different points on the reaction surface.

7. The method of claim 3 , wherein said reductant comprises a mixture of ascorbic acid and maleic acid.

8. The method of claim 1 , wherein an amount of NO delivered to the patient is calculated based upon the alveolar volume of the patient and a desired concentration of NO to be delivered to said patient.

9. A device for controlled intermittent or continuous delivery of NO to the lung of a human patient in need thereof by inhalation, said device comprising:

a reaction chamber in fluid communication by inhalation with the patient;

a rotatable reaction surface having solid nitrite salt or a reductant disposed thereon; and

a controllable liquid dispensing system adapted to deliver liquid aqueous droplets comprising a dissolved nitrite salt or reductant at a controlled pulsed rate onto the rotatable reaction surface to form NO for delivery to the patient by inhalation, the liquid aqueous droplets having a volume in the range of 10 picoliters to 100 picoliters;

wherein delivery of NO to the lung is controlled by controlling the frequency of the droplets, and the frequency is up to 12 MHz; and

the rotatable reaction surface is rotated to advance to a new position after each local reaction from the liquid aqueous droplets thereby delivering the liquid aqueous droplets to all of the available solid nitrite salt or reductant disposed on the rotatable reaction surface.

10. The device of claim 9 , wherein the liquid dispensing system is adapted to spray the droplets from an aqueous solution.

11. The device of claim 10 , wherein the controllable liquid dispensing system sprays droplets at a rate based upon the alveolar volume of the patient and a concentration of NO to be inhaled by the patient.

12. The device of claim 10 , further comprising a reservoir adapted to contain said aqueous solution.

13. The device of claim 9 , wherein the sodium nitrite or reductant is coated to the rotatable reaction surface.

14. The device of claim 9 , wherein the rotatable reaction surface is adapted to be rotated by a movement system.

15. The device of claim 9 , wherein the reductant is ascorbic acid or maleic acid or mixtures thereof.

16. The device of claim 9 , wherein the device is portable and adapted to be located at or proximate to the patient.

17. The device of claim 16 , further comprising a pump adapted to pump ambient air through the reaction chamber.

18. The device of claim 17 , further comprising a pump controller adapted to control the operation of the pump for continuous or pulsed operation.

19. The device of claim 17 , further comprising a membrane filter adapted to reduce the oxygen content of the ambient air pumped into the reaction chamber, said filter being in fluid communication between the pump and the reaction chamber.

20. The device of claim 16 , further comprising a ventilator adapted to provide an inspiratory gas to the patient through the device for controlled delivery of NO.

21. The device of claim 20 , further comprising a removing device adapted to remove NO 2 from the inspiratory gas delivered to the patient.

22. The device of claim 20 , further including an input device adapted to set the desired concentration of nitric oxide to be delivered to the patient, and a flow sensor adapted to determine the flow of gas being provided by the ventilator, wherein the amount of nitric oxide delivered to the patient is based on the desired concentration entered into the input device.

23. The device of claim 16 , further including an input device adapted to set the desired concentration of nitric oxide to be provided to a patient, and a flow sensor adapted to determine the flow of gas going to the patient through the device for controlled delivery of NO from a gas delivery system, wherein the amount of nitric oxide delivered to the patient is based on said concentration and side flow of gas.

Assignments (33)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 10, 2026
From: MALLINCKRODT HOSPITAL PRODUCTS IP UNLIMITED COMPANY
To: MALLINCKRODT PHARMACEUTICALS IRELAND LIMITED COMPANY
Reel/Frame 075393/0361 →
CORRECTIVE ASSIGNMENT TO CORRECT THE INCLUSION OF US PATENT 10828415 AND REMOVE IT FROM THE LISTING PREVIOUSLY RECORDED ON REEL 73375 FRAME 395. ASSIGNOR(S) HEREBY CONFIRMS THE SECURITY INTEREST. Recorded Mar 6, 2026
From: MALLINCKRODT PHARMACEUTICALS IRELAND LIMITED
To: GOLDMAN SACHS BANK USA, AS ADMINISTRATIVE AGENT
Reel/Frame 075021/0263 →
CORRECTIVE ASSIGNMENT TO CORRECT THE INCLUSION OF US PATENT 10828415 AND REMOVE IT FROM THE LISTING PREVIOUSLY RECORDED ON REEL 72331 FRAME 1. ASSIGNOR(S) HEREBY CONFIRMS THE SECURITY INTEREST. Recorded Mar 6, 2026
From: MALLINCKRODT PHARMACEUTICALS IRELAND LIMITED
To: COMPUTERSHARE TRUST COMPANY, NATIONAL ASSOCIATION
Reel/Frame 075021/0204 →
SECURITY INTEREST Recorded Oct 28, 2025
From: MALLINCKRODT PHARMACEUTICALS IRELAND LIMITED
To: GOLDMAN SACHS BANK USA, AS ADMINISTRATIVE AGENT
Reel/Frame 073375/0395 →
RELEASE OF SECURITY INTEREST Recorded Aug 14, 2025
From: ACQUIOM AGENCY SERVICES LLC
To: 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
Reel/Frame 072324/0740 →
SECURITY INTEREST Recorded Aug 1, 2025
From: MALLINCKRODT PHARMACEUTICALS IRELAND LIMITED
To: COMPUTERSHARE TRUST COMPANY, NATIONAL ASSOCIATION
Reel/Frame 072331/0001 →
RELEASE OF PATENT SECURITY INTERESTS RECORDED AT REEL 035454, FRAME 0768 Recorded Nov 16, 2023
From: DEUTSCHE BANK AG NEW YORK BRANCH, AS COLLATERAL AGENT
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
Reel/Frame 065610/0035 →
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
Reel/Frame 065601/0347 →
RELEASE OF PATENT SECURITY INTERESTS RECORDED AT REEL 049822, FRAME 0674 Recorded Nov 16, 2023
From: DEUTSCHE BANK AG NEW YORK BRANCH, AS COLLATERAL AGENT
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
Reel/Frame 065609/0454 →
RELEASE OF SECURITY INTERESTS IN PATENTS AT REEL 060389/FRAME 0913 Recorded Nov 15, 2023
From: WILMINGTON SAVINGS FUND SOCIETY, FSB, AS SECOND LIEN COLLATERAL AGENT
To: OCERA THERAPEUTICS LLC (F/K/A OCERA THERAPEUTICS, INC.); MALLINCKRODT LLC; MALLINCKRODT ENTERPRISES LLC; MALLINCKRODT PHARMA IP TRADING UNLIMITED COMPANY; SPECGX LLC; STRATATECH CORPORATION; SUCAMPO PHARMA AMERICAS LLC; VTESSE LLC; MALLINCKRODT PHARMACEUTICALS IRELAND LIMITED
Reel/Frame 065583/0465 →
SECURITY INTEREST Recorded Nov 15, 2023
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
To: ACQUIOM AGENCY SERVICES LLC
Reel/Frame 065595/0376 →
NOTICE OF GRANT OF SECURITY INTEREST IN INTELLECTUAL PROPERTY Recorded Jun 22, 2022
From: MALLINCKRODT ENTERPRISES LLC; MALLINCKRODT LLC; SPECGX LLC; OCERA THERAPEUTICS, INC.; STRATATECH CORPORATION; SUCAMPO PHARMA AMERICAS LLC; VTESSE LLC; MALLINCKRODT PHARMACEUTICALS IRELAND LIMITED; MALLINCKRODT PHARMA IP TRADING UNLIMITED COMPANY
To: DEUTSCHE BANK AG NEW YORK BRANCH
Reel/Frame 060434/0536 →
SECURITY INTEREST Recorded Jun 17, 2022
From: MALLINCKRODT ENTERPRISES LLC; MALLINCKRODT LLC; SPECGX LLC; OCERA THERAPEUTICS, INC.; STRATATECH CORPORATION; SUCAMPO PHARMA AMERICAS LLC; VTESSE LLC; MALLINCKRODT PHARMACEUTICALS IRELAND LIMITED
To: WILMINGTON SAVINGS FUND SOCIETY, FSB, AS SECOND LIEN COLLATERAL AGENT
Reel/Frame 060389/0913 →
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.)
Reel/Frame 060389/0839 →
SECURITY INTEREST Recorded Dec 10, 2019
From: MALLINCKRODT ARD IP LIMITED; MALLINCKRODT HOSPITAL PRODUCTS IP LIMITED; SPECGX LLC; OCERA THERAPEUTICS, INC.; MALLINCKRODT PHARMA IP TRADING DESIGNATED ACTIVITY COMPANY; STRATATECH CORPORATION; VTESSE INC.; MALLINCKRODT LLC
To: WILMINGTON SAVINGS FUND SOCIETY, FSB, AS SECOND LIEN COLLATERAL AGENT
Reel/Frame 051256/0829 →
NOTICE OF GRANT OF SECURITY INTEREST IN INTELLECTUAL PROPERTY Recorded Jul 22, 2019
From: MALLINCKRODT HOSPITAL PRODUCTS IP LIMITED
To: DEUTSCHE BANK AG NEW YORK BRANCH, AS COLLATERAL AGENT
Reel/Frame 049822/0674 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 5, 2016
From: MALLINCKRODT CRITICAL CARE FINANCE INC.
To: MALLINCKRODT PHARMA IP TRADING DAC
Reel/Frame 038038/0009 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 5, 2016
From: MALLINCKRODT IP
To: MALLINCKRODT HOSPITAL PRODUCTS IP LIMITED
Reel/Frame 038009/0016 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 5, 2016
From: INO THERAPEUTICS LLC
To: THERAKOS, INC.
Reel/Frame 038008/0956 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 5, 2016
From: THERAKOS, INC.
To: MALLINCKRODT CRITICAL CARE FINANCE INC.
Reel/Frame 038008/0824 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 5, 2016
From: MALLINCKRODT PHARMA IP TRADING DAC
To: MALLINCKRODT IP
Reel/Frame 038009/0058 →
SECURITY INTEREST Recorded Apr 19, 2015
From: INO THERAPEUTICS LLC
To: DEUTSCHE BANK AG NEW YORK BRANCH
Reel/Frame 035454/0768 →
RELEASE OF SECURITY INTEREST Recorded Apr 17, 2015
From: CREDIT SUISSE AG, CAYMAN ISLANDS BRANCH
To: INO THERAPEUTICS LLC
Reel/Frame 035453/0513 →
RELEASE OF SECURITY INTEREST Recorded Apr 17, 2015
From: CREDIT SUISSE AG, CAYMAN ISLANDS BRANCH
To: INO THERAPEUTICS LLC
Reel/Frame 035453/0487 →
PATENT SECURITY AGREEMENT (SECOND LIEN) Recorded Mar 11, 2014
From: INO THERAPEUTICS LLC
To: CREDIT SUISSE AG, CAYMAN ISLANDS BRANCH, AS ADMINISTRATIVE AGENT
Reel/Frame 032426/0848 →
PATENT SECURITY AGREEMENT (FIRST LIEN) Recorded Mar 11, 2014
From: INO THERAPEUTICS LLC
To: CREDIT SUISSE AG, CAYMAN ISLANDS BRANCH, AS ADMINISTRATIVE AGENT
Reel/Frame 032426/0747 →
RELEASE OF SECURITY INTEREST Recorded Feb 18, 2014
From: CREDIT SUISSE AG, CAYMAN ISLANDS BRANCH, AS COLLATERAL AGENT
To: INO THERAPEUTICS LLC
Reel/Frame 032274/0768 →
RELEASE OF SECURITY INTEREST Recorded Feb 14, 2014
From: CREDIT SUISSE AG, CAYMAN ISLANDS BRANCH, AS COLLATERAL AGENT
To: IKARIA INC.; INO THERAPEUTICS LLC
Reel/Frame 032264/0517 →
SECURITY AGREEMENT Recorded Jul 10, 2013
From: IKARIA, INC.; IKARIA ACQUISITION INC.; INO THERAPEUTICS LLC
To: CREDIT SUISSE AG, AS COLLATERAL AGENT
Reel/Frame 030764/0549 →
SECURITY AGREEMENT Recorded Jul 31, 2011
From: IKARIA, INC.; INO THERAPEUTICS LLC
To: CREDIT SUISSE AG, CAYMAN ISLANDS BRANCH, AS COLLATERAL AGENT
Reel/Frame 026676/0954 →
RELEASE OF SECURITY INTERESTS Recorded Jun 24, 2010
From: CREDIT SUISSE AG, CAYMAN ISLANDS BRANCH, AS COLLATERAL AGENT
To: INO THERAPEUTICS, LLC; IKARIA RESEARCH, INC. (F/K/A IKARIA, INC.)
Reel/Frame 024576/0868 →
SECURITY AGREEMENT Recorded Apr 2, 2007
From: INO THERAPEUTICS LLC; IKARIA, INC.
To: CREDIT SUISSE, AS COLLATERAL AGENT
Reel/Frame 019094/0784 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 16, 2006
From: MONTGOMERY, FREDERICK J.; BATHE, DUNCAN P. L.
To: INO THERAPEUTICS LLC
Reel/Frame 017664/0795 →