METHOD OF PREVENTING FIBRIN CLOTS IN PULMONARY TISSUE THROUGH THE USE OF AEROSOLIZED ANTICOAGULANTS

• US 20110070167A1
• Filed: 09/10/2010
• Published: 03/24/2011
• Est. Priority Date: 02/20/2004
• Status: Abandoned Application

• Current Assignee: Board of Regents of the University of Texas System (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:
  US12/879,235
• Publication Number:
  US 20110070167A1
• Time in Patent Office: Days
• US Class Current: 424/43
• 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

1-24. -24. (canceled)

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

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

26. The method of claim 25, wherein the antithrombin III is administered by inhalation.

27. The method of claim 26, wherein the heparin is administered by inhalation.

28. The method of claim 26, wherein the heparin is administered intravenously.

29. The method of claim 25, wherein the antithrombin III is administered intravenously.

30. The method of claim 29, wherein the heparin is administered by inhalation.

31. The method of claim 29, wherein the heparin is administered intravenously.

32. The method of claim 25, wherein the antithrombin III and heparin are administered concurrently.

33. The method of claim 25, wherein the antithrombin III is administered at a dose of about 10-300 U/kg of body weight.

34. The method of claim 33, wherein the antithrombin III is administered at a dose of about 25-125 U/kg of body weight.

35. The method of claim 25, wherein the heparin is administered at a dose of about 10-300 U/kg of body weight.

36. The method of claim 35, wherein the heparin is administered at a dose of about 25-125 U/kg of body weight.

37. The method of claim 25, wherein the antithrombin III is plasma derived antithrombin III.

38. The method of claim 25, wherein the antithrombin III is recombinantly produced antithrombin III.

39. The method of claim 38, wherein the recombinant antithrombin III is transgenically produced antithrombin III.

40. The method of claim 25, wherein the heparin is plasma derived heparin.

41. The method of claim 25, wherein the heparin is administered using an ultrasonic nebulizer.

42. The method of claim 25, wherein the heparin is administered using a dry powder inhalation system.

43. The method of claim 25, wherein the heparin is administered using a jet aerosol.

44. The method of claim 25, wherein said method of treatment is effective in increasing the pulmonary gas exchange fraction.

45. The method of claim 25, wherein said method of treatment is effective in decreasing vascular permeability.

46. The method of claim 25, wherein the lung injury was caused by smoke inhalation.

47. The method of claim 25, wherein the lung injury was caused by burn damage to the lungs.

48. The method of claim 25, wherein the lung injury is septic acute lung injury.

49. The method of claim 25, wherein the lung injury is acute respiratory distress syndrome (ARDS).

50. The method of claim 25, wherein the lung injury is in response to exposure to a biological agent.

51. The method of claim 50, wherein the biological agent is Pseudomonas pneumonia.

52. The method of claim 25, wherein the lung injury is in response to exposure to asbestos.

53. The method of claim 25, wherein the lung injury is in response to exposure to a viral agent.

54. The method of claim 25, wherein the lung injury comprises lung neoplasia.

55. The method of claim 25, wherein the lung injury comprises pleural neoplasia.

56. The method of claim 25, wherein the lung injury comprises interstitial lung disease.

57. The method of claim 25, wherein the lung injury comprises organizing pleuitis.

58. A method for treating acute lung injury in a subject by administering a therapeutically effective amount of aerosolized heparin such that the lung injury is treated, the improvement comprising administering antithrombin III.

59. The method of claim 58, wherein the antithrombin III is administered by inhalation.

60. The method of claim 58, wherein the antithrombin III is administered intravenously.