NITRIC OXIDE DELIVERY DEVICES

• US 20160339197A1
• Filed: 08/02/2016
• Published: 11/24/2016
• Est. Priority Date: 03/30/2012
• Status: Active Grant

• Current Assignee: Board of Regents of the University of Michigan (University of Michigan)
• Original Assignee: Board of Regents of the University of Michigan (University of Michigan)
• Inventors: Meyerhoff, Mark E., Hofler, Lajos, Koley, Dipankar, Ren, Hang
• Granted Patent: US 10,543,337 B2
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: A61K 33/00 Medicinal preparations containing inorganic active ingredients
• CPC Class Codes: A61M 1/1698 Blood oxygenators with or without heat-exchangers intracorporal A61M1/1678; manufacturing of membranes therefor B01D67/00; semi-permeable membranes for separation processes characterised by their properties B01D69/00; semi-permeable membranes characterised by their material B01D71/00
• CPC Class Codes: A61M 1/342 Adding solutions to the blood, e.g. substitution solutions for preventing coagulation A61M1/3672
• CPC Class Codes: A61M 1/3462 Circuits for the preparation thereof
• CPC Class Codes: A61M 16/12 by mixing different gases
• CPC Class Codes: A61M 2025/0057 Catheters delivering medicament other than through a conventional lumen, e.g. porous walls or hydrogel coatings
• CPC Class Codes: A61M 2202/0208 Oxygen
• CPC Class Codes: A61M 2202/0275 Nitric oxide [NO]
• CPC Class Codes: A61M 25/0043 characterised by structural features
• CPC Class Codes: A61M 35/00 Devices for applying media, e.g. remedies, on the human body devices for handling toiletry or cosmetic substances A45D; absorbent pads, e.g. swabs, A61F13/15
• CPC Class Codes: C25B 1/00 Electrolytic production of inorganic compounds or non-metals
• CPC Class Codes: C25B 15/08 Supplying or removing reactants or electrolytes; Regeneration of electrolytes

Abstract

A gas delivery device includes a nitric oxide generating system. The system has a medium including i) a source of nitrite ions, or ii) a source of nitrite ions and a Cu(II)-ligand complex. A working electrode is in contact with the medium, wherein i) when the medium includes the source of nitrite ions, the working electrode is a copper containing conductive material or a base material coated with a copper containing conductive material, or ii) when the medium includes the source of nitrite ions and the Cu(II)-ligand complex, the working electrode is platinum, gold, carbon, a carbon coated material, and/or mercury. A reference/counter electrode is in contact with the medium and electrically isolated from the working electrode. An inlet conduit is to deliver oxygen gas to the medium, and an outlet conduit is to transport a stream of oxygen gas and nitric oxide from the medium.

Claims

1. A gas delivery device, comprising:

a nitric oxide generating system, including;

a medium including i) a source of nitrite ions, or ii) a source of nitrite ions and a Cu(II)-ligand complex;

a working electrode in contact with the medium, wherein i) when the medium includes the source of nitrite ions, the working electrode is a copper containing conductive material or a base material coated with a copper containing conductive material, or ii) when the medium includes the source of nitrite ions and the Cu(II)-ligand complex, the working electrode is selected from the group consisting of platinum, gold, carbon, a carbon coated material, and mercury; and

a reference/counter electrode in contact with the medium and electrically isolated from the working electrode;

an inlet conduit to deliver oxygen gas to the medium; and

an outlet conduit to transport a stream of oxygen gas and nitric oxide from the medium.

2. The gas delivery device as defined in claim 1, further comprising:

an oxygenator operatively connected to the outlet conduit, the oxygenator including a membrane permeable to oxygen gas and nitric oxide, the membrane positioned to receive the stream of oxygen gas and nitric oxide from the outlet conduit at a first surface and to deliver a cleaned stream of oxygen gas and nitric oxide through a second surface.

3. The gas delivery device as defined in claim 2 wherein the oxygenator is a blood oxygenator that further includes:

a housing;

a plurality of the membranes positioned within the housing and operatively connected to the outlet conduit, each of the membranes being a hollow polymeric fiber that is permeable to oxygen gas and nitric oxide, wherein an interior surface of each hollow polymeric fiber is the first surface and an exterior surface of each hollow polymeric fiber is the second surface;

a blood inlet to introduce blood into the housing adjacent to the second surfaces; and

a blood exit to transport blood from the housing.

4. The gas delivery device as defined in claim 2 wherein the oxygenator is an inhalation unit that further includes a patient delivery system.

5. The gas delivery device as defined in claim 1, further comprising an inhalation unit operatively connected to the outlet conduit.

6. The gas delivery device as defined in claim 1 wherein:

the medium includes the source of nitrite ions;

the medium is an aqueous solution or a hydrogel; and

the source of nitrite ions is any water soluble, inorganic nitrite salt.

7. The gas delivery device as defined in claim 1 wherein:

the medium includes the source of nitrite ions and the Cu(II)-ligand complex;

the medium is an aqueous solution or a hydrogel;

the source of nitrite ions is any water soluble, inorganic nitrite salt; and

the Cu(II)-ligand complex is selected from the group consisting of Cu(II)-tri(2-pyridylmethyl)amine, Cu(II)-tri(2-dimethylamino)ethyl]amine, Cu(II)-tri(2-pyridylmethyl)phosphine, and combinations thereof.

8. A method for generating nitric oxide, comprising:

applying a cathodic voltage to a working electrode positioned in contact with a medium including a source of nitrite ions and a Cu(II)-ligand complex, thereby reducing the Cu(II)-ligand complex to a Cu(I)-ligand complex which reacts with nitrite from the source of nitrite ions to form the nitric oxide.

9. The method as defined in claim 8, further comprising modulating a flux of the generated nitric oxide by any of altering an amount of a surface area of the working electrode that is exposed to the medium, or altering a concentration of any of the Cu(II)-ligand complex or the source of nitrite ions in the medium, or altering a magnitude of the cathodic voltage over time.

10. The method as defined in claim 8 wherein the applying of the cathodic voltage is accomplished at predetermined intervals.

11. The method as defined in claim 8 wherein the applying of the cathodic voltage includes:

applying a first cathodic voltage to increase NO production for a predetermined time period; and

then

applying a second cathodic voltage that is less negative than the first cathodic voltage to decrease NO production after the predetermined time period has expired.