Method and apparatus for nitric oxide generation

• US 20030062043A1
• Filed: 08/28/2002
• Published: 04/03/2003
• Est. Priority Date: 09/05/2001
• Status: Active Grant

• Current Assignee: Vero Biotech LLC
• Original Assignee: GENO LLC
• Inventors: Wheeler, David, Fine, David H., Jarvis, George, MacDonald, Stephen J., Rolfe, Jonathan L., Rounbehler, David
• Granted Patent: US 7,040,313 B2
• Time in Patent Office: Days
• US Class Current: 128/203.12
• CPC Class Codes: A61K 33/00 Medicinal preparations containing inorganic active ingredients
• CPC Class Codes: A61K 33/24 Heavy metals; Compounds thereof
• CPC Class Codes: A61K 33/30 Zinc; Compounds thereof
• CPC Class Codes: A61K 33/34 Copper; Compounds thereof
• CPC Class Codes: A61K 9/007 Pulmonary tract; Aromatherapy
• CPC Class Codes: A61K 9/2031 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers
• CPC Class Codes: A61K 9/205 Polysaccharides, e.g. alginate, gums; Cyclodextrin
• CPC Class Codes: A61K 9/7007 Drug-containing films, membranes or sheets A61K9/0041, A61K9/0043, A61K9/006, A61K9/0063 take precedence
• CPC Class Codes: A61M 16/10 Preparation of respiratory gases or vapours
• CPC Class Codes: A61M 16/12 by mixing different gases
• CPC Class Codes: A61M 2016/1035 the anaesthetic agent concentration
• CPC Class Codes: A61M 2202/0275 Nitric oxide [NO]
• CPC Class Codes: A61M 2209/06 Packaging for specific medical equipment
• CPC Class Codes: C01B 21/24 Nitric oxide (NO) C01B21/203 takes precedence

Abstract

Inhalation of low levels of nitric oxide can rapidly and safely decrease pulmonary hypertension in mammals. Precise delivery of nitric oxide at therapeutic levels of 20 to 100 ppm and inhibition of reaction of nitric oxide with oxygen to form toxic impurities such as nitrogen dioxide can provide effective inhalation therapy for pulmonary hypertension.

Claims

1. An apparatus for delivering a therapeutic gas including nitric oxide comprising:

a receptacle including a therapeutic gas outlet and a non-electrolytic nitric oxide precursor receiver; and

a transport gas inlet fluidly communicating from a source of a transport gas to the therapeutic gas outlet through the non-electrolytic nitric oxide precursor receiver.

2. The apparatus of claim 1 wherein the transport gas inlet includes a gas distributor in the non-electrolytic nitric oxide precursor receiver.

3. The apparatus of claim 1 further including a therapeutic gas delivery system fluidly connectable to the therapeutic gas outlet.

4. The apparatus of claim 3 wherein the therapeutic gas delivery system includes a therapeutic gas purifier.

5. The apparatus of claim 4 wherein the therapeutic gas purifier includes a filter.

6. The apparatus of claim 3 wherein the therapeutic gas delivery system includes a mask fluidly connectable to the therapeutic gas outlet.

7. The apparatus of claim 1 wherein the mask is connectable to a mammal.

8. The apparatus of claim 1 wherein the source of the transport gas includes a gas flow controller.

9. A method of delivering nitric oxide to a mammal comprising:

non-electrolytically generating a therapeutic gas from a nitric oxide precursor, wherein the therapeutic gas includes nitric oxide and is substantially devoid of nitrogen dioxide; and

transporting the therapeutic gas to a mammal.

10. The method of claim 9 wherein non-electrolytically generating the therapeutic gas includes contacting the nitric oxide precursor with a buffer solution to form a mixture.

15. The method of claim 9 wherein transporting the therapeutic gas includes delivering at least 1 ppm nitric oxide to the mammal.

16. The method of claim 9 wherein transporting the therapeutic gas includes delivering less than 100 ppm of nitric oxide to the mammal.

17. The method of claim 9 wherein the therapeutic gas contains 20 to 60 ppm of nitric oxide.

18. The method of claim 9 further comprising controlling a flow rate of a transport gas through the precursor in the range of 1 to 20 liters per minute.

19. The method of claim 9 further comprising controlling a flow rate of the transport gas is in the range of 1 to 5 liters per minute.

20. The method of claim 9 wherein the transport gas includes oxygen.

21. The method of claim 9 wherein the transport gas includes ambient air.

22. The method of claim 9 wherein the transport gas includes an air and oxygen mixture.

23. The method of claim 9 further comprising passing the therapeutic gas through a gas purifier prior to transporting the gas.

24. The method of claim 23 wherein the gas purifier includes a pyrolizer, a reduction oxidation agent, or a semi-permeable membrane.

25. The method of claim 9 wherein the nitric oxide precursor includes a precursor salt.

26. The method of claim 25 wherein the precursor salt includes a nitrite salt.

27. The method of claim 9 wherein the nitric oxide precursor includes a nitrite salt selected from a group consisting of potassium nitrite, sodium nitrite, rubidium nitrite, strontium nitrite, barium nitrite, calcium nitrite, copper nitrite and zinc nitrite.

28. The method of claim 26 wherein the nitrite salt includes sodium nitrite.

29. The method of claim 9 wherein generating the therapeutic gas includes releasing nitric oxide from the precursor for over at least one hour.

30. The method of claim 9 wherein generating the therapeutic gas includes releasing nitric oxide from the precursor over a period of time from one hour to seven days.

31. The method of claim 9 wherein generating the therapeutic gas includes releasing nitric oxide from the precursor over a period of time from two hours to 24 hours.

32. The method of claim 23 wherein the gas purifier includes a ferrous salt.

33. The method of claim 9 wherein the therapeutic gas is substantially devoid of nitrogen dioxide.

34. The method of claim 9 wherein generating the therapeutic gas includes contacting the nitric oxide precursor with a nitric oxide releasing salt.

35. The method of claim 34 wherein the nitric oxide releasing salt includes a ferrous salt.

11. The method of 10 wherein the buffer solution includes a pH buffer combination selected from a group consisting of acetic acid/acetate, hydrochloric acid/chloride, hydrochloric acid/citrate, citric acid-phosphate, phosphoric acid/phosphate and citric acid/citrate.

12. The method of 10 wherein the buffer solution maintains a pH of the mixture in the range of 4 to 7.

13. The method of 10 wherein the buffer solution maintains a pH of the mixture in the range of 6.5-6.9.

14. The method of 9 wherein transporting the therapeutic gas includes contacting the transport gas with the mixture..

36. A kit comprising a nitric oxide precursor and instructional material describing a method of generating a therapeutic gas and transporting the therapeutic gas, the therapeutic gas comprising nitric oxide and being substantially devoid of nitrogen dioxide.

37. The kit of claim 36 wherein the nitric oxide precursor includes a precursor salt.

38. The kit of claim 37 wherein the precursor salt includes a nitrite salt.

39. The kit of claim 36 wherein the nitric oxide precursor includes a nitrite salt selected from a group consisting of potassium nitrite, sodium nitrite, rubidium nitrite, strontium nitrite, barium nitrite, calcium nitrite, copper nitrite and zinc nitrite.

40. The kit of claim 39 wherein the nitrite salt includes sodium nitrite.

41. The kit of claim 36 wherein generating the therapeutic gas includes releasing nitric oxide from the precursor over a period of time from one hour to seven days.

42. The kit of claim 41 wherein generating the therapeutic gas includes releasing nitric oxide from the precursor over a period of time from two hours to 24 hours.