Stable S-nitrosothiol formulations

• US 20070243262A1
• Filed: 12/21/2006
• Published: 10/18/2007
• Est. Priority Date: 12/21/2005
• Status: Abandoned Application

• Current Assignee: Nitrox LLC (Marvell Technology Group Limited)
• Original Assignee: Nitrox LLC (Marvell Technology Group Limited)
• Inventors: Stamler, Jonathan, Hurley, Kevin, Bovet, Li
• Application Number:
  US11/644,388
• Publication Number:
  US 20070243262A1
• Time in Patent Office: Days
• US Class Current: 424/499
• CPC Class Codes: A61K 38/063 Glutathione
• CPC Class Codes: A61K 47/12 Carboxylic acids; Salts or anhydrides thereof
• CPC Class Codes: A61K 9/0073 Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy; nasal sprays A61K9/0043; inhalation of vapours of volatile or heated drugs, e.g. essential oils or nicotine, A61K9/007; devices A61M
• CPC Class Codes: A61K 9/008 comprising drug dissolved or suspended in liquid propellant for inhalation via a pressurized metered dose inhaler [MDI]
• CPC Class Codes: A61K 9/145 with organic compounds
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 11/08 Bronchodilators
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 7/02 Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/04 Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
• CPC Class Codes: A61P 9/12 Antihypertensives

Abstract

The invention provides stable S-nitrosothiol, such as S-nitrosoglutathione, formulations for long term storage and in vivo delivery of S-nitrosothiols. The invention provides stable aerosol formulations comprising S-nitrosothiol, such as S-nitrosoglutathione, and methods of treating patients in need of S-nitrosothiol, such as S-nitrosoglutathione, and/or nitric oxide treatment.

Claims

1. A composition comprising S-nitrosoglutathione micronized into particles of about 1.5 μ

m to about 6.0 μ

m.

2. The composition of claim 1 wherein the S-nitrosoglutathione has a purity greater than 95.0% as determined by HPLC.

3. The composition of claim 3, wherein the composition contains less than 5.0% reduced and oxidized L-glutathione.

4. The composition of claim 3, wherein the composition contains less than 2.5% glutathione.

5. The composition of claim 3, wherein the composition contains less than 2.5% glutathione disulfide.

6. The composition of claim 3, wherein the composition contains less than 2.0% H₂O.

7. An S-nitrosoglutathione formulation comprising an S-nitrosoglutathione and a hydrofluorocarbon propellant.

8. The formulation of claim 7, wherein the S-nitrosoglutathione is present in particles of about 1.5 μ

m to about 6.0 μ

m.

9. The formulation of claim 7, wherein the hydrofluorocarbon propellant is HFA 134 or HFA 227.

10. The formulation of claim 7, further comprising one or more co-solvents.

11. The formulation of claim 10, wherein the co-solvent is ethanol.

12. The formulation of claim 11, wherein the ethanol is present in an amount of about 1% to about 20%.

13. The formulation of claim 7, further comprising a surfactant.

14. The formulation of claim 13, wherein the surfactant is oleic acid, salts of oleic acid or oleyl alcohol.

15. The formulation of claim 13, wherein the surfactant is present in an amount of about 1% to about 2% w/w with respect to the amount of S-nitrosoglutathione.

16. The formulation of claim 7, wherein the S-nitrosoglutathione is present in an amount of about 0.1 mg/actuation to about 2.0 mg/actuation.

17. The formulation of claim 16, wherein the S-nitrosoglutathione is present in an amount of about 0.15 mg/actuation to about 1.5 mg/actuation.

18. The formulation of claim 7, wherein the S-nitrosoglutathione is administered in a unit dosage of about 0.1 mg/day to about 160.0 mg/day.

19. The formulation of claim 18, wherein the S-nitrosoglutathione is administered in an amount of about 1.5 mg/day to about 25 mg/day.

20. The formulation of claim 7, filled in a metal canister.

21. The formulation of claim 20, wherein the canister has part or all of its internal metallic surfaces made of stainless steel, anodised aluminum lined with an inert organic coating, or anodised aluminum not lined with an inert organic coating.

22. The formulation of claim 21, wherein the inert organic coating selected from epoxy-phenol resins, perfluoroalkoxyalkane, perfluoroalkoxyalkylene, perfluoroalkylenes such as polytetrafluoroethylene, fluorinated-ethylene-propylene, polyether sulfone and a copolymer fluorinated-ethylene-propylene polyether sulfone.

23. An S-nitrosoglutathione formulation comprising an S-nitrosoglutathione, HFA 134, 5% ethanol and 2% oleic acid.

24. An S-nitrosoglutathione formulation comprising an S-nitrosoglutathione micronized into particles of about 1.5 μ

m to about 6.0 μ

m, HFA 134, 5% ethanol and 2% oleic acid.