IP Library Granted Patent US 10,537,697
Granted Patent B2
US 10,537,697 · App. 15/008,048 · Granted Jan 21, 2020

Method and apparatus for generating nitric oxide for medical use

Inventors: Frederick Montgomery (Sun Prairie, WI); Duncan Bathe (Fitchburg, WI)
Assignee: MALLINCKRODT HOSPITAL PRODUCTS IP LIMITED
A61M16/10A61K33/00A61M16/0003A61M16/0057A61M16/107A61M2016/003A61M2016/0021A61M2016/0039A61M2016/102A61M2202/0275A61M2205/33
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Quick Facts
Patent No.
US 10,537,697
App. No.
15/008,048
Granted
Jan 21, 2020
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 (36)

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

delivering aqueous droplets comprising dissolved nitrite salt compound via pulses from a first liquid dispenser to a location on a rotatable reaction surface at a first position in a reaction chamber in fluid communication with the lung by inhalation of the human patient;

rotating the rotatable reaction surface to a second position;

delivering droplets comprising a liquid reductant via pulses from a second liquid dispenser to substantially the same location on the rotatable reaction surface in the reaction chamber as the aqueous droplets comprising dissolved nitrite salt compound;

generating NO gas by reacting the dissolved nitrite salt with the reductant in the reaction chamber; and

delivering an amount of the generated NO to the lung of the human patient;

wherein the reductant comprises ascorbic acid and maleic acid at a 1:1 molar ratio.

2. The method of controlled delivery of nitric oxide (NO) to the lung of a human patient in need thereof by inhalation according to claim 1 , wherein generating NO comprises continuous reaction of the nitrite salt and the reductant.

3. The method of controlled delivery of nitric oxide (NO) to the lung of a human patient in need thereof by inhalation according to claim 1 , wherein the NO is delivered at a concentration in a range of 5 ppm to 80 ppm.

4. The method of controlled delivery of nitric oxide (NO) to the lung of a human patient in need thereof by inhalation according to claim 1 , wherein the nitrite salt compound is sodium nitrite.

5. The method of controlled delivery of nitric oxide (NO) to the lung of a human patient in need thereof by inhalation according to claim 1 , wherein the droplets are delivered at a rate based upon an alveolar volume of the patient and a concentration of NO to be inhaled by the patient.

6. The method of controlled delivery of nitric oxide (NO) to the lung of a human patient in need thereof by inhalation according to claim 1 , further comprising the step of controlling the amount of NO delivered to the lung of the patient by controlling the frequency at which the aqueous nitrite salt compound droplets are contacted with the liquid reductant.

7. A device for controlled intermittent or continuous delivery of nitric oxide (NO) gas to the lung of a human patient in need thereof by inhalation, the device comprising:

a reaction chamber comprising a rotatable reaction surface in fluid communication with the lung by inhalation with the human patient;

a first controllable liquid dispensing system adapted to spray aqueous droplets comprising dissolved nitrite salt compound to a location in the reaction chamber at a pulsed rate into contact with a liquid reductant;

a second controllable liquid dispensing system adapted to spray at a pulsed rate the liquid reductant at substantially the same location on the rotatable reaction surface in the reaction chamber as the aqueous droplets comprising dissolved nitrite salt compound; and

an outlet for discharging NO gas from the reaction chamber for delivery to the patient;

wherein delivery of NO gas to the lung is controlled by controlling the frequency at which the aqueous nitrite salt compound droplets are contacted with the liquid reductant, and

wherein the reductant comprises ascorbic acid and maleic acid at a 1:1 molar ratio.

8. The device for controlled intermittent or continuous delivery of nitric oxide (NO) to the lung of a human patient in need thereof by inhalation according to claim 7 , wherein the first controllable liquid dispensing system is comprised of at least one micropump.

9. The device for controlled intermittent or continuous delivery of nitric oxide (NO) to the lung of a human patient in need thereof by inhalation according to claim 8 , wherein the second controllable liquid dispensing system is comprised of at least one micropump.

10. The device for controlled intermittent or continuous delivery of nitric oxide (NO) to the lung of a human patient in need thereof by inhalation according to claim 7 , wherein the droplets have a volume in the range of 10 picoliters to 100 picoliters.

11. The device for controlled intermittent or continuous delivery of nitric oxide (NO) to the lung of a human patient in need thereof by inhalation according to claim 7 , wherein the nitrite salt compound is sodium nitrite.

12. The device for controlled intermittent or continuous delivery of nitric oxide (NO) to the lung of a human patient in need thereof by inhalation according to claim 7 , further comprising a ventilator adapted to provide inspiratory gas to the patient through the device for controlled delivery of NO.

13. The device for controlled intermittent or continuous delivery of nitric oxide (NO) to the lung of a human patient in need thereof by inhalation according to claim 7 , 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 provided by the ventilator, wherein the amount of NO delivered to the patient is based on the desired concentration entered into the input device.

14. A device for controlled intermittent or continuous delivery of nitric oxide (NO) gas to the lung of a human patient in need thereof by inhalation, the device comprising:

a reaction chamber comprising a rotatable reaction surface in fluid communication with the lung by inhalation with the patient;

a first controllable liquid dispensing system adapted to spray aqueous droplets comprising dissolved nitrite salt compound in the range of 10 picoliters to 100 picoliters at a pulsed rate into contact with a liquid reductant;

a second controllable liquid dispensing system adapted to spray at a pulsed rate the liquid reductant at substantially the same location on the rotatable reaction surface in the reaction chamber as the aqueous droplets comprising dissolved nitrite salt compound;

an outlet for discharging NO gas from the reaction chamber for delivery to the patient;

a ventilator in fluid communication with the outlet and adapted to provide inspiratory gas to the patient through the device for controlled delivery of NO gas;

wherein delivery of NO gas to the lung is controlled by controlling the frequency at which the aqueous nitrite salt compound droplets are contacted with the liquid reductant;

wherein the nitrite salt compound is sodium nitrite and the liquid reductant is ascorbic acid and maleic acid; and

wherein the ascorbic acid and maleic acid are at a 1:1 molar ratio.

15. The device for controlled intermittent or continuous delivery of nitric oxide (NO) to the lung of a human patient in need thereof by inhalation according to claim 14 , wherein the first controllable liquid dispensing system is comprised of at least one micropump.

16. The device for controlled intermittent or continuous delivery of nitric oxide (NO) to the lung of a human patient in need thereof by inhalation according to claim 14 , wherein the second controllable liquid dispensing system is comprised of at least one micropump.

Assignments (20)
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 043601, FRAME 0025 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 065610/0233 →
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 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 PATENTS Recorded Aug 18, 2017
From: MALLINCKRODT HOSPITAL PRODUCTS IP LIMITED
To: DEUTSCHE BANK AG NEW YORK BRANCH, AS COLLATERAL AGENT
Reel/Frame 043601/0025 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 12, 2016
From: MALLINCKRODT PHARMA IP TRADING DAC
To: MALLINCKRODT IP
Reel/Frame 040706/0389 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 12, 2016
From: MALLINCKRODT CRITICAL CARE FINANCE INC.
To: MALLINCKRODT PHARMA IP TRADING DAC
Reel/Frame 040706/0326 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 12, 2016
From: THERAKOS, INC.
To: MALLINCKRODT CRITICAL CARE FINANCE INC.
Reel/Frame 040705/0579 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 12, 2016
From: INO THERAPEUTICS LLC
To: THERAKOS, INC.
Reel/Frame 040705/0447 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 12, 2016
From: MALLINCKRODT IP
To: MALLINCKRODT HOSPITAL PRODUCTS IP LIMITED
Reel/Frame 040706/0446 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 1, 2016
From: MONTGOMERY, FREDERICK; BATHE, DUNCAN
To: INO THERAPEUTICS LLC
Reel/Frame 038168/0677 →
Cited By (1)
US 12,252,398