Treatment of vascular thrombosis and restenosis with inhaled nitric oxide

• US 6,063,407 A
• Filed: 02/16/1995
• Issued: 05/16/2000
• Est. Priority Date: 02/16/1995
• Status: Expired due to Fees

• Current Assignee: Massachusetts General Hospital (Mass General Brigham, Inc.)
• Original Assignee: The General Hospital Corporation (Mass General Brigham, Inc.)
• Inventors: Bloch, Kenneth D., Zapol, Warren M.
• Primary Examiner(s): Harrison, Robert H.
• Application Number:
  US08/389,304
• Time in Patent Office: 1,916 Days
• Field of Search: 424/718, 424/43, 424/94.4, 435/215, 435/216, 435/359, 514/263, 514/262, 514/258
• US Class Current: 424/718
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/505 Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
• CPC Class Codes: A61K 31/52 Purines, e.g. adenine
• CPC Class Codes: A61K 33/00 Medicinal preparations containing inorganic active ingredients
• CPC Class Codes: A61K 38/446 Superoxide dismutase (1.15)
• 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 9/08 Vasodilators for multiple indications
• 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

Abstract

Disclosed are methods of treating, inhibiting or preventing vascular thrombosis or arterial restenosis in a mammal. The disclosed methods include causing the mammal to inhale a therapeutically-effective concentration of gaseous nitric oxide (NO). Also disclosed are methods that include the administration of the following types of agents in conjunction with inhaled nitric oxide: compounds that potentiate the beneficial effects of inhaled nitric oxide, and antithrombotic agents that complement or supplement the beneficial effects of inhaled nitric oxide.

Claims

1. A method for treating, inhibiting or preventing arterial restenosis in a mammal, which method comprises the steps of:

(a) identifying a mammal that has an existing arterial restenosis or is at risk for developing arterial restenosis; and

(b) causing said mammal to inhale therapeutically effective concentration of gaseous NO; and

(c) administering to said mammal a therapeutically effective amount of a phosphodiesterase inhibitor without inducing acute systemic hypotension.

2. The method of claim 1, wherein said mammal is a human.

3. The method of claim 1, wherein said mammal has undergone or is preparing to undergo a vascular interventional procedure.

4. The method of claim 3, wherein said vascular interventional procedure is selected from the group consisting of angioplasty, coronary artery surgery and coronary artery stents.

5. The method of claim 4 wherein said angioplasty is percutaneous transluminal coronary angioplasty (PTCA).

6. The method of claim 1, wherein said NO is inhaled in a predetermined concentration range.

7. The method of claim 6, wherein said concentration range is 0.1 ppm to 300 ppm.

8. The method of claim 6, wherein said concentration range is 1.0 ppm to 200 ppm.

9. The method of claim 6, wherein said concentration range is 20 ppm to 100 ppm.

10. The method of claim 1, wherein said gaseous NO is inhaled as a mixture comprising NO, O₂, and N₂ gases.

11. The method of claim 10, wherein said mixture comprises between 20% and 99% O₂ gas by volume.

12. The method of claim 10, wherein said O₂ is mixed with said NO immediately before said mixture is inhaled by said mammal.

13. The method of claim 1, wherein said second compound is selected from the group consisting of a phosphodiesterase inhibitor and superoxide dismutase.

14. The method of claim 13, wherein said phosphodiesterase inhibitor is selected from the group consisting of 2-o-propoxyphenyl-8-azapurin-6-one, dipyridamole and theophyline.

15. The method of claim 1, wherein said gaseous NO is inhaled in the absence of tobacco smoke.