Airway Administration of Activated Protein C in Inflammatory Conditions Affecting the Respiratory Tract
The present invention provides methods for the local treatment of acute and chronic extravascular pulmonary fibrin deposition and/or reducing unwanted effects associated with systemic administration of anticoagulants to a subject via airway administration to the subject by intratracheal, intrabronchial or intraalveolar routes of human activated protein C or biologically active derivatives thereof.
1 . A method for treating or preventing extravascular fibrin deposition in the airways, in particular the alveolar or bronchoalveolar spaces, in a human subject comprising administering to the subject human activated protein C or a biologically active derivative thereof, via the airway by means of intratracheal, intrabronchial or intraalveolar administration.
2 . The method of claim 1 , wherein the fibrin deposition is caused by an inflammatory lung disease.
3 . The method of claim 2 , wherein the inflammatory lung disease is selected from the group consisting of: ALI, ARDS, pneumonia, acute bronchoalveolar diseases, chronic bronchoalveolar diseases, fibrosing alveolitis or bronchial asthma.
4 . The method of any of the preceding claims, wherein the inflammatory lung disease is related to a condition selected from the group consisting of: direct or indirect pulmonary trauma, pancreatitis, aspiration pneumonitis, sepsis, severe sepsis and/or septic shock and/or drug induced acute lung insufficiency.
5 . The method of any of the preceding claims, wherein the activated protein C is administered by bronchoalveolar lavage with a solution of the activated protein C.
6 . The method of any of the preceding claims, wherein the activated protein C is administered by blind tracheal washing with a solution of the activated protein C.
7 . The method of any of the preceding claims, wherein the activated protein C is administered by causing the inhalation of a nebulized solution of the activated protein C.
8 . The method of any of the preceding claims, wherein the activated protein C is administered by causing the inhalation of the activated protein C in nebulized powder form.
9 . The method of any of the preceding claims, wherein the activated protein C is administered by direct application of the activated protein C during bronchoscopy.
10 . The method of any of claims 1 through 9 wherein the human is an adult.
11 . The method of any of claims 1 through 9 wherein the human is a child.
12 . The method of any of the preceding claims, wherein the APC is administered in an amount of from 0.1 μg/kg to about 10 mg/kg body weight per day.
13 . The method of any of claims 1 through 9 further comprising administering to the human subject an anticoagulant systemically as an adjuvant therapy.
14 . The method of claim 13 wherein the human is an adult.
15 . The method of claim 13 wherein the human is a child.