Conversion of nitrogen dioxide (NO2) to nitric oxide (NO)

• US 20080317874A1
• Filed: 03/21/2008
• Published: 12/25/2008
• Est. Priority Date: 03/23/2007
• Status: Active Grant

• Current Assignee: Vero Biotech LLC
• Original Assignee: GENO LLC
• Inventors: Rounbehler, David P., Fine, David H., Vasquez, Greg
• Granted Patent: US 7,947,227 B2
• Time in Patent Office: Days
• US Class Current: 424/718
• CPC Class Codes: A61M 16/10 Preparation of respiratory gases or vapours
• CPC Class Codes: A61M 2016/1025 the O2 concentration
• CPC Class Codes: A61M 2202/0275 Nitric oxide [NO]
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: A61P 9/12 Antihypertensives
• CPC Class Codes: C01B 21/24 Nitric oxide (NO) C01B21/203 takes precedence

Abstract

A nitric oxide delivery system, which includes a gas bottle having nitrogen dioxide in air, converts nitrogen dioxide to nitric oxide and employs a surface-active material, such as silica gel, coated with an aqueous solution of antioxidant, such as ascorbic acid. A nitric oxide delivery system may be used to generate therapeutic gas including nitric oxide for use in delivering the therapeutic gas to a mammal.

Claims

1. A kit for generating a therapeutic gas including nitric oxide for use in delivering the therapeutic gas to a mammal comprising:

a diffusion cell configured to be connected to a source of nitrogen dioxide;

a permeation tube connected to the diffusion cell; and

a receptacle configured to attach to the permeation tube, the receptacle including an inlet, an outlet, and a surface-active material coated with an antioxidant, wherein the inlet is configured to receive the flow of nitrogen dioxide from the permeation tube and fluidly communicate the flow to the outlet through the surface-active material to convert the gaseous nitrogen dioxide to nitric oxide at ambient temperature.

2. The kit of claim 1, wherein the source of nitrogen dioxide is liquid nitrogen dioxide.

3. The kit of claim 1, wherein diffusion cell is configured to provide the nitrogen dioxide at a diffusion rate of 200,000 ng per minute.

4. The kit of claim 1, wherein the diffusion cell is made of stainless steel or plastic.

5. The kit of claim 1, wherein the permeation tube length is scaled to provide a predetermined dose of nitrogen dioxide at a particular temperature.

6. The kit of claim 5, wherein the permeation tube further comprises a movable, non-permeable sheath over the length of the tube.

7. The kit of claim 6, wherein the sheath is configured to be removed prior to use.

8. The kit of claim 1, wherein the permeation tube is connected to the diffusion cell through a diffusion needle.

9. The kit of claim 8, wherein the diffusion needle is a narrow bore diffusion needle.

10. The kit of claim 8, wherein the diffusion needle further comprises holes on the side of needle and an outer sheath surrounding the holes, wherein the sheath has slots fitted around the needle configured to be turned to uncover the uncover the desired hole.

11. The kit of claim 10, wherein the holes on the side of the needle are at ¼

, ½

or ¾

mark.

12. The kit of claim 8, wherein the diffusion cell is connected to multiple permeation tube through multiple narrow bore diffusion needles.

13. The kit of claim 1, wherein the receptacle comprises a cartridge.

14. The kit of claim 1, wherein the surface-active material is saturated with the antioxidant.

15. The kit of claim 1, wherein the surface-active material comprises a substrate that retains water.

16. The kit of claim 1, wherein the surface-active material comprises a silica gel.

17. The kit of claim 1, wherein the antioxidant comprises ascorbic acid.

18. The kit of claim 1, wherein the antioxidant comprises alpha tocopherol or gamma tocopherol.

19. The kit of claim 1, wherein the receptacle is a first receptacle, the kit further comprising a second receptacle including a second inlet, a second outlet, and a second surface-active material coated with an aqueous solution of an antioxidant, wherein the second inlet is configured to receive the flow from the first receptacle and fluidly communicate the flow to the second outlet through the second surface-active material to convert the gaseous nitrogen dioxide to nitric oxide at ambient temperature.

21. The kit of claim 18, further comprising a gas bottle having nitrogen dioxide and capable of providing diffusing gaseous nitrogen dioxide into an air flow.

22. The kit of claim 18, wherein the receptacle is placed on the low pressure side of the pressure regulator.

23. The kit of claim 18, wherein the receptacle is a first receptacle, the kit further comprising a second receptacle including a second inlet, a second outlet, and a second surface-active material coated with an aqueous solution of an antioxidant, wherein the second inlet is configured to receive the flow from the first receptacle and fluidly communicate the flow to the second outlet through the second surface-active material to convert the gaseous nitrogen dioxide to nitric oxide at ambient temperature.

24. The kit of claim 18, wherein the pressure regulator includes an inlet port and an outlet port that connects the receptacle with a gas bottle having nitrogen dioxide in air.

25. The kit of claim 18, wherein the receptacle comprises a cartridge.

26. The kit of claim 18, wherein the surface-active material is saturated with the aqueous solution of the antioxidant.

27. The kit of claim 18, wherein the surface-active material comprises a substrate that retains water.

28. The kit of claim 18, wherein the surface-active material comprises a silica gel.

29. The kit of claim 18, wherein the antioxidant comprises ascorbic acid.

30. The kit of claim 18, wherein the antioxidant comprises alpha tocopherol or gamma tocopherol.

20. A kit for generating a therapeutic gas including nitric oxide for use in delivering the therapeutic gas to a mammal comprising:

a pressure regulator configured to be connected to a source of nitrogen dioxide;

a receptacle configured to attach to the pressure regulator, the receptacle including an inlet, an outlet, and a surface-active material coated with an aqueous solution of an antioxidant, wherein the inlet is configured to receive the flow from a source of gaseous nitrogen dioxide and fluidly communicate the flow to the outlet through the surface-active material to convert the gaseous nitrogen dioxide to nitric oxide at ambient temperature,

wherein the receptacle is configured to attach to the gas bottle having nitrogen dioxide in air and capable of providing a flow of gaseous nitrogen dioxide and air.

31. A method of providing a therapeutic amount of nitric oxide to a mammal comprising:

diffusing nitrogen dioxide into a gas flow;

exposing the nitrogen dioxide to a surface-active material coated with an antioxidant to convert the gaseous nitrogen dioxide to nitric oxide at ambient temperature; and

transporting the nitric oxide in a therapeutic amount to a mammal.

32. The method of claim 31, wherein the nitrogen dioxide is generated from liquid nitrogen dioxide.

33. The method of claim 31, wherein diffusing nitrogen dioxide into a gas flow includes providing the nitrogen dioxide at a diffusion rate of 200,000 ng per minute.

34. The method of claim 31, wherein diffusing nitrogen dioxide into a gas flow includes providing a predetermined dose of nitrogen dioxide at a particular temperature.

35. The method of claim 31, wherein the surface-active material is saturated with the antioxidant.

36. The method of claim 31, wherein the surface-active material comprises a substrate that retains water.

37. The method of claim 31, wherein the surface-active material comprises a silica gel.

38. The method of claim 31, wherein the antioxidant comprises ascorbic acid.

39. The method of claim 31, wherein the antioxidant comprises alpha tocopherol or gamma tocopherol.

40. The method of claim 31, further comprising contacting the nitric oxide a second surface-active material coated with an antioxidant immediately prior to inhalation by the mammal.