Method of preventing fibrin clots in pulmonary tissue through the use of aerosolized anticoagulants

• US 20050192226A1
• Filed: 02/14/2005
• Published: 09/01/2005
• Est. Priority Date: 02/20/2004
• Status: Abandoned Application

• Current Assignee: GTC Biotherapeutics, Inc., Board of Regents of the University of Texas System (University of Texas System), The University of Texas Medical Branch at Galveston (University of Texas System)
• Original Assignee: Board of Regents of the University of Texas System (University of Texas System)
• Inventors: Murakami, Kazunori, Traber, Daniel L., Enkhbaatar, Perenlei
• Application Number:
  US11/057,522
• Publication Number:
  US 20050192226A1
• Time in Patent Office: Days
• US Class Current: 514/1.5
• 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 31/727 Heparin; Heparan
• CPC Class Codes: A61K 38/57 from animals; from humans A61K38/553, A61K38/556 take precedence
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/12 Mucolytics
• CPC Class Codes: A61P 11/16 Central respiratory analeptics
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• 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 9/14 Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers

Abstract

ATIII is a serine proteinase inhibitor (serpin) with anti-coagulant, anti-inflammatory, anti-proliferative and anti-angiogenic properties. The invention features methods of treating a subject having lung injury due to burns and smoke inhalation by administering a synergistic combination of antithrombin III and heparin through pulmonary delivery means.

Claims

1. A method of treating acute lung injury in a subject, comprising:

administering by inhalation a therapeutically effective amount of antithrombin III and Heparin such that the lung injury is treated.

2. The method of claim 1, wherein the lung injury is septic acute lung injury.

3. The method of claim 1, wherein the lung injury is acute respiratory distress syndrome (ARDS).

4. The method of claim 1, wherein the lung injury is in response to exposure to a viral agent.

5. The method of claim 1, wherein the biological agent is Pseudomonas pneumonia.

6. The method of claim 1, wherein the lung injury is in response to one or more of smoke and asbestos.

7. The method of claim 1, wherein the antithrombin III and Heparin combination is administered using an ultrasonic nebulizer.

8. The method of claim 1, wherein the antithrombin III is plasma derived antithrombin III.

9. The method of claim 1, wherein the antithrombin III is recombinantly produced antithrombin III.

10. The method of claim 9, wherein the recombinant ed antithrombin III is transgenically produced antithrombin III.

11. The method of claim 1, wherein the subject is administered more than one dose of the antithrombin III.

12. The method of claim 1, wherein the antithrombin III is administered at a dose of about 10-300 U/kg of body weight.

13. The method of claim 1, wherein the anfithrombin III is administered at a dose of about 25-125 U/kg of body weight.

14. The method of claim 1, wherein the lung injury is treated both with ATIII and heparin.

15. The method of claim 1, wherein the lung injury treated was caused by smoke inhalation.

16. The method of claim 1, wherein the lung injury treated was caused by burn damage to the lungs.

19. The method of claim 1, wherein the heparin is plasma derived heparin.

20. The method of claim 1, wherein the heparin is recombinantly produced heparin.

21. The method of claim 9, wherein the recombinant heparin is transgenically produced heparin.

22. The method of claim 1, wherein the subject is administered more than one dose of the heparin.

23. The method of claim 1, wherein the heparin is administered at a dose of about 10-300 U/kg of body weight.

24. The method of claim 1, wherein the heparin is administered at a dose of about 25-125 U/kg of body weight.

17. A process for treating a human acute lung injury with a composition of matter containing a protein, said protein being encoded by a transgene DNA construct comprising ATIII.

18. A process for treating a human acute lung injury with a composition of matter containing a protein, said protein being encoded by a transgene DNA construct comprising ATIII., an improvement comprising treating a patient with a substantially pharmaceutically pure composition of said protein with an effective amount of heparin.