IP Library Granted Patent US 9,278,111
Granted Patent B2
US 9,278,111 · App. 14/307,664 · Granted Mar 8, 2016

Method and apparatus for generating nitric oxide for medical use

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Quick Facts
Patent No.
US 9,278,111
App. No.
14/307,664
Granted
Mar 8, 2016
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 (30)

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

delivering droplets comprising nitrite salt dissolved in aqueous droplets to a first position on a moveable reaction surface at a frequency up to 12 MHz, wherein the moveable reaction surface comprises a solid reductant disposed on the moveable reaction surface;

generating NO through the reaction between the nitrite salt and the reductant;

moving the reaction surface to a second position;

delivering droplets comprising nitrite salt dissolved in aqueous droplets to the second position on the moveable reaction surface; and

controlling the amount of NO delivered to the lung of the patient by controlling the frequency of the droplets delivered to the moveable reaction surface.

2. The method of claim 1 , wherein generating NO comprises continuous reaction of the nitrite salt and the reductant.

3. The method of claim 1 , wherein controlling the frequency of the droplets delivered to the moveable reaction surface is via a controllable micro pump.

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

5. The method of claim 1 , wherein the nitrite salt is sodium nitrite, and, wherein the reductant comprises ascorbic acid, maleic acid or a mixture thereof.

6. The method of claim 5 , wherein said reductant comprises a mixture of ascorbic acid and maleic acid.

7. The method of claim 1 , wherein the moveable reaction surface is a disc or tape.

8. The method of claim 1 , wherein the lung has an alveolar volume in the range of 300 mL to 400 mL at rest.

9. The method of claim 1 , wherein the moveable reaction surface is rotatable.

10. 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.

11. The method of claim 1 , wherein the droplets are delivered at a rate based upon the alveolar volume of the patient and a concentration of NO to be inhaled by the patient.

12. The method of claim 1 , wherein generating NO comprises pulsed reaction of the nitrite salt and the reductant.

13. A device for controlled intermittent or continuous delivery of nitric oxide (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 moveable reaction surface having a reductant disposed thereon; and

a controllable liquid dispensing system adapted to spray liquid aqueous droplets comprising a dissolved nitrite salt at a controlled continuous or pulsed rate onto the reaction surface to form NO for delivery to the patient by inhalation;

wherein delivery of NO to the lung is controlled by controlling the frequency of the droplets; and

wherein the moveable reaction surface is adapted to move to advance to a new position after reaction from the liquid aqueous droplets, thereby delivering the liquid aqueous droplets to reductant disposed on the new position of the moveable reaction surface.

14. The device of claim 13 , wherein the droplets have a volume in the range of 10 picoliters to 100 picoliters.

15. The device of claim 13 , wherein the frequency is up to 12 MHz.

16. The device of claim 13 , wherein the moveable reaction surface is rotatable.

17. The device of claim 13 , wherein the wherein the reductant comprises ascorbic acid, maleic acid or a mixture thereof.

18. The device of claim 13 , wherein the moveable reaction surface is a disc or tape.

19. A system comprising the device of claim 13 and a ventilator adapted to provide an inspiratory gas to the patient through the device for controlled delivery of NO.

20. The system of claim 19 , further comprising an input device adapted to set the desired concentration of NO 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 NO delivered to the patient is based on the desired concentration entered into the input device.

Assignments (22)
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
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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
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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 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
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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
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NOTICE OF GRANT OF SECURITY INTEREST IN INTELLECTUAL PROPERTY Recorded Jun 22, 2022
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To: DEUTSCHE BANK AG NEW YORK BRANCH
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RELEASE OF SECURITY INTEREST Recorded Jun 17, 2022
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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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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
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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
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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
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ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 5, 2016
From: INO THERAPEUTICS LLC
To: THERAKOS, INC.
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ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 5, 2016
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From: MALLINCKRODT CRITICAL CARE FINANCE INC.
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ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 5, 2016
From: THERAKOS, INC.
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ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 5, 2016
From: MALLINCKRODT IP
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ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 27, 2016
From: MONTGOMERY, FREDERICK J.; BATHE, DUNCAN
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SECURITY INTEREST Recorded Apr 19, 2015
From: INO THERAPEUTICS LLC
To: DEUTSCHE BANK AG NEW YORK BRANCH
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