IP Library Granted Patent US 11,623,054
Granted Patent B2
US 11,623,054 · App. 17/078,821 · Granted Apr 11, 2023

Systems and method for delivery of therapeutic gas to patients, in need thereof, receiving breathing gas from a ventilator that varies at least pressure and/or flow using enhanced therapeutic gas (NO) flow measurement

Inventors: Jaron M. Acker (Madison, WI); Craig R. Tolmie (Stoughton, WI)
Assignee: MALLINCKRODT PHARMACEUTICALS IRELAND LIMITED
A61M16/00A61M16/0003A61M16/0057A61M16/024A61M16/06A61M16/12A61M16/122A61M16/201A61M2016/003A61M2016/0039A61M2202/0275A61M2202/0283A61M2205/15A61M2205/3334A61M2205/35
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Quick Facts
Patent No.
US 11,623,054
App. No.
17/078,821
Granted
Apr 11, 2023
Kind
B2
Abstract

Provided herein are systems and methods for delivery of therapeutic gas to patients, in need thereof, by receiving breathing gas from a high frequency ventilator using at least enhanced therapeutic gas (e.g., nitric oxide, NO, etc.) flow measurement. At least some of these enhanced therapeutic gas flow measurements can be used to address some surprising phenomenon that may, at times, occur when wild stream blending therapeutic gas into breathing gas a patient receives from a breathing circuit affiliated with a high frequency ventilator. Utilizing at least some of these enhanced therapeutic gas flow measurements the dose of therapeutic gas wild stream blended into breathing gas that the patient receives can at least be more accurate and/or under delivery of therapeutic gas into the breathing gas can be avoided and/or reduced.

Claims (47)

1. A nitric oxide delivery system for delivering therapeutic gas into breathing gas in an inspiratory limb of a patient breathing circuit affiliated with a high frequency ventilator or ventilation techniques which provide reverse and/or oscillations in inspiratory pressure or flow, the nitric oxide delivery system comprising:

at least one control valve for providing a flow of nitric oxide gas;

an injector module comprising:

an injector body having a first opening and a second opening, the first opening and the second opening being configured to couple the injector module to the inspiratory limb of a breathing circuit enabling patient breathing gas in the breathing circuit to flow through the first opening and second opening;

a therapeutic gas inlet in the injector body, the therapeutic gas inlet being configured to receive the flow of nitric oxide gas and enable injection of the nitric oxide gas into the injector module, and in turn into patient breathing gas in the inspiratory limb of the breathing circuit;

at least one NO flow sensor in fluid communication with the therapeutic gas inlet; and

a control system in communication with the at least one NO flow sensor to receive flow information from the at least one NO flow sensor, wherein the control system is operable to:

(i) detect use of the high frequency ventilator;

(ii) identify the flow information as missing and interpolate the missing flow information; and/or

(iii) identify the flow information as reverse flow.

2. The nitric oxide delivery system of claim 1 , wherein the therapeutic gas inlet receives the flow of nitric oxide gas from a nitric oxide source, via a conduit.

3. The nitric oxide delivery system of claim 2 , wherein the nitric oxide source is a cylinder storing NO or an NO generator.

4. The nitric oxide delivery system of claim 3 , wherein the NO generator is operable to generate the nitric oxide gas by reaction of a NO-releasing agent with a reductant.

5. The nitric oxide delivery system of claim 4 , wherein the NO-releasing agent is nitrogen dioxide and the reductant is ascorbic acid.

6. The nitric oxide delivery system of claim 1 , wherein the control system is operable to use the flow information to ensure that a desired dose of NO is delivered into the injector module, and in turn into patient breathing gas in the inspiratory limb of the breathing circuit.

7. The nitric oxide delivery system of claim 1 , wherein the control system is operable to use the flow information to ensure that a desired dose of NO is not under delivered and/or under dosed.

8. The nitric oxide delivery system of claim 1 , further comprising a check valve that is one or more of (i) in fluid communication with the therapeutic gas inlet of the injector module and (ii) is integral to the injector module.

9. The nitric oxide delivery system of claim 1 , wherein the at least one NO flow sensor is at least one bi-directional flow sensor.

10. The nitric oxide delivery system of claim 9 , wherein the at least one bi-directional flow sensor is a thermal mass flow meter or a thermal dispersion flow meter.

11. The nitric oxide delivery system of claim 1 , wherein the inspiratory limb is also an expiratory limb in the breathing circuit.

12. The nitric oxide delivery system of claim 1 , wherein the NO flow sensor is downstream of the control valve in the nitric oxide delivery system.

13. The nitric oxide delivery system of claim 1 , wherein the control valve is upstream of the NO flow sensor in the nitric oxide delivery system.

14. The nitric oxide delivery system of claim 1 , wherein the therapeutic gas inlet receives the flow of nitric oxide gas via a conduit, and the conduit has one or more of (i) an internal cross-sectional diameter of about 1/32 of an inch to about ¼ of an inch and (ii) an internal portion within the nitric oxide delivery system and an external portion outside the nitric oxide delivery system, the internal portion of the conduit having a cross-sectional diameter that is substantially the same as a cross-sectional diameter of the external portion of the conduit.

15. The nitric oxide delivery system of claim 1 , further comprising at least a second NO flow sensor in fluid communication with the therapeutic gas inlet and in communication with the control system, wherein the control system receives flow information from the NO flow sensors and detects a leak when the flow information from the NO flow sensors does not match.

16. The nitric oxide delivery system of claim 15 , wherein the flow of nitric oxide gas is increased if a leak is detected.

17. A nitric oxide delivery system for delivering therapeutic gas into breathing gas in an inspiratory limb of a patient breathing circuit affiliated with a high frequency ventilator or ventilation techniques which provide reverse and/or oscillations in inspiratory pressure or flow, the nitric oxide delivery system comprising:

a nitric oxide gas source operable to provide nitric oxide gas;

at least one control valve for providing a flow of the nitric oxide gas;

an injector module comprising:

an injector body having a first opening and a second opening, the first opening and the second opening being configured to couple the injector module to the inspiratory limb of a breathing circuit enabling patient breathing gas in the breathing circuit to flow through the first opening and second opening;

a therapeutic gas inlet in the injector body, the therapeutic gas inlet being configured to receive the flow of the nitric oxide gas and enable injection of the nitric oxide gas into the injector module, and in turn into patient breathing gas in the inspiratory limb of the breathing circuit;

a conduit operable to provide the flow of the nitric oxide gas to the therapeutic gas inlet from the nitric oxide gas source;

at least one bi-directional NO flow sensor in fluid communication with the therapeutic gas inlet, the at least one bi-directional NO flow sensor being capable of measuring flow in a forward direction and in a reverse direction through the therapeutic gas inlet; and

a control system in communication with the at least one bi-directional NO flow sensor to receive bi-directional flow information comprising at least forward flow information and reverse flow information from the at least one bi-directional NO flow sensor.

18. The nitric oxide delivery system of claim 17 , wherein the nitric oxide source is a cylinder storing NO or an NO generator.

19. The nitric oxide delivery system of claim 18 , wherein the NO generator is operable to generate the nitric oxide gas by reaction of a NO-releasing agent with a reductant.

20. The nitric oxide delivery system of claim 19 , wherein the NO-releasing agent is nitrogen dioxide and the reductant is ascorbic acid.

21. The nitric oxide delivery system of claim 17 , wherein the control system is operable to use the flow information to ensure that a desired dose of NO is delivered into the injector module, and in turn into patient breathing gas in the inspiratory limb of the breathing circuit.

22. The nitric oxide delivery system of claim 17 , wherein the control system is operable to use the flow information to ensure that a desired dose of NO is not under delivered and/or under dosed.

23. The nitric oxide delivery system of claim 17 , further comprising a check valve that is one or more of (i) in fluid communication with the therapeutic gas inlet of the injector module and (ii) is integral to the injector module.

24. The nitric oxide delivery system of claim 17 , wherein the at least one bi-directional flow sensor is a thermal mass flow meter (thermal dispersion flow meter).

25. The nitric oxide delivery system of claim 17 , wherein the inspiratory limb is also an expiratory limb in the breathing circuit.

26. The nitric oxide delivery system of claim 17 , wherein the NO flow sensor is downstream of the control valve in the nitric oxide delivery system.

27. The nitric oxide delivery system of claim 17 , wherein the control valve is upstream of the NO flow sensor in the nitric oxide delivery system.

28. The nitric oxide delivery system of claim 17 , wherein the conduit has one or more of (i) an internal cross-sectional diameter of about 1/32 of an inch to about ¼ of an inch and (ii) an internal portion within the nitric oxide delivery system and an external portion outside the nitric oxide delivery system, the internal portion of the conduit having a cross-sectional diameter that is substantially the same as a cross-sectional diameter of the external portion of the conduit.

29. The nitric oxide delivery system of claim 17 , further comprising at least a second NO flow sensor in fluid communication with the therapeutic gas inlet and in communication with the control system, wherein the control system receives flow information from the NO flow sensors and detects a leak when the flow information from the NO flow sensors does not match.

30. The nitric oxide delivery system of claim 29 , wherein the flow of the nitric oxide gas is increased if a leak is detected.

Assignments (9)
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 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 →
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 →
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 →
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 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 3, 2021
From: MALLINCKRODT HOSPITAL PRODUCTS IP UNLIMITED COMPANY
To: MALLINCKRODT PHARMACEUTICALS IRELAND LIMITED
Reel/Frame 056433/0640 →