Use of Docosatrienes, Resolvins and Their Stable Analogs in the Treatment of Airway Diseases and Asthma
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Abstract
The present invention is generally drawn to novel isolated therapeutic agents, termed resolving, generated from the interaction between a dietary omega-3 polyunsaturated fatty acid (PUFA) such as eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA), cyclooxygenase-II (COX-2) and an analgesic, such as aspirin (ASA). Surprisingly, careful isolation of compounds generated from the combination of components in an appropriate environment provide di- and tri-hydroxy EPA or DHA compounds having unique structural and physiological properties. The present invention therefore provides for many new useful therapeutic di- or tri-hydroxy derivatives of EPA or DHA (resolvins) that diminish, prevent, or eliminate inflammation or PMN migration, for example. The present invention also provides methods of use, methods of preparation, and packaged pharmaceuticals for use as medicaments for the compounds disclosed throughout the specification.
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Citations
23 Claims
- 1. An isolated compound selected from:
- 2. An isolated compound of the formula:
- 12. A compound selected from:
- 13. A compound of the formula:
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23. A method of treating an individual suffering from or susceptible to a disease or condition selected from asthma, airway inflammation, chronic bronchitis, bronchiectasis, cystic fibrosis, non-cystic fibrosis-related bronchiectasis, eosinophilic lung diseases including parasitic infection, idiopathic eosinophilic pneumonias and Churg-Strauss vasculitis, allergic bronchopulmonary aspergillosis, allergic inflammation of the respiratory tract, including rhinitis, and sinusitis, bronchiolitis, bronchiolitis obliterans, bronchiolitis obliterans with organizing pneumonia, eosinophilic granuloma, Wegener'"'"'s granulomatosis, sarcoidosis, hypersensitivity pneumonitis, idiopathic pulmonary fibrosis, pulmonary manifestations of connective tissue diseases, acute or chorionic lung injury, and adult respiratory distress syndrome, comprising the steps of administering to the individual in need thereof:
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a. a therapeutically effective amount of a COX-2 inhibitor; and
b. a therapeutically effective amount of an omega-3 polyunsaturated fatty acid.
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Specification