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Use of aerosolized antithrombin to treat acute lung injury

An acute lung injury and antithrombin technology, which is applied to medical preparations containing active ingredients, peptide/protein components, pharmaceutical formulas, etc., can solve the problems of no improvement in lung injury treatment and no inhibition of fibrin

Inactive Publication Date: 2007-04-11
GTC生物治疗有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Therefore, in the absence of adequate levels of antithrombin in the airways, aerosolized heparin will not inhibit fibrin formation, resulting in little improvement in the treatment of lung injury from smoke or combustion

Method used

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  • Use of aerosolized antithrombin to treat acute lung injury
  • Use of aerosolized antithrombin to treat acute lung injury
  • Use of aerosolized antithrombin to treat acute lung injury

Examples

Experimental program
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Embodiment 1

[0081] Recombinantly produced ATIII was dissolved in saline (42 mg / ml). Ewe sheep (n=24) were used. After 48 breaths of cotton smoke (11 ). All animals used 100% O 2 Mechanical ventilation (Tidal volume 15ml / kg, 30 breaths / min, PEEP 5cmH 2 O). At 2, 4, 8, 12, 16, and 20 hours after injury, recombinant antithrombin (n=6), argatroban (n=8), or the same volume of normal saline (n=10) were sprayed with an ultrasonic nebulizer. No animals died during the study. PaO 2 / FiO 2 Ratio, pulmonary shunt, and histological airway obstruction score were all reduced by antithrombin and argatroban. However, histopathological changes and lung wet / dry weight ratio were only reduced by antithrombin but not by argatroban.

[0082] Materials and methods

[0083] Material

[0084] Human recombinant antithrombin (ATIII) (7, 8) was a gift from GTC Biotherapeutics (Framingham, MA). Argatroban was purchased from Daiichi Pharmaceutical Co. (Tokyo, Japan). All other...

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Abstract

The invention features methods of treating a subject having a lung disorder such as lung inflammation and injury, by administering antithrombin III through pulmonary delivery.

Description

[0001] priority claim [0002] This application claims priority from USSN 60 / 538,678, filed January 23, 2004, the contents of which are incorporated herein by reference. Background of the invention [0003] In inflammatory lung disease, fibrin can be observed in the airways. Formation of alveolar fibrin is known to be a marker of acute and / or chronic lung disease. In inflammatory conditions, plasma exudate enters the airways due to increased permeability of pulmonary vessels. Fibrinogen in extravasated plasma will be activated by tissue factor expressed on activated alveolar macrophages (1) and epithelial cells (2), which leads to clot formation in the airways. Intrabronchial fibrin has several roles in lung pathology. First, it blocks ventilation. We have shown that more than 40% of the bronchi and bronchioles are obstructed by fibrin-containing casts after smoke inhalation and pneumonia in sheep (3). When parts of the lungs are blocked, gas e...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/48
Inventor 村上和纪佩伦雷·恩赫巴塔罗伯特·A·科克斯哈尔·A·霍金斯莉莲·D·特拉伯丹尼尔·L·特拉伯
Owner GTC生物治疗有限公司
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