Treatment of Mucocillary Clearance in Cystic Fibrosis Patients and Respiratory Inflammation by Using Alkylaryl Polyether Alcohol Polymers
The present invention provides a novel method to use alkylaryl polyether alcohol polymers as antioxidants to block oxidant reactions and prevent tissue injury and disease that are related to overproduction of partially reduced dioxygen (O2) species, such as chronic pulmonary inflammation, myocardial infarction and stroke, adult respiratory distress syndrome, and oxygen toxicity of the lung. This invention shows that by inhibiting the activation of nuclear transcription factor NF-?B, alkylaryl polyether alcohol polymers can inhibit the cellular production of pro-inflammatory cytokines TNF-?, IL-1, IL-6, IL-8, and the growth factor GM-CSF. Also, this invention provides methods for using alkylaryl polyether alcohol polymers as mucolytic agents for breaking up cystic fibrosis sputum or mucous, as inhibitors of monocyte tumor necrosis factor, and as inhibitors of production of IL-8 in patients with cystic fibrosis.
One main strategy to treat diseases which are related to overproduction of partially reduced O2 species, such as adult respiratory distress syndrome and oxygen toxicity of the lung, is to introduce exogenous antioxidant compounds which will restore oxidant-antioxidant balance in biologic and chemical systems. Alkylaryl polyether alcohol polymers are potent antioxidants that can be used pharmaceutically in treating respiratory inflammations.
Cystic fibrosis (CF) is the most common lethal recessive genetic disease in the United States. The airway cells in CF patients are at risk of oxidant-mediate injury, and the major cause of mortality and morbidity in these patients is progressive pulmonary disease. This invention provides the method of using alkylaryl polyether alcohol polymers for mucocillary clearance in CF patients.
Stage of Development
Patents (#5,512,270, #6,165,445, #5,474,760, #5,830,436, #5,840,237, #6,024,940, and #5,849,263) have been issued from the U.S. Patent and Trademark Office. Patents have been issued under the PCT with nationalization to Austria (0910390), New Zealand (263986), Canada (2,216,789 and 2,159,485), Europe (0910390), Australia (717537), Italy (0910390), Ireland (0910390), Great Britain (0910390) and France (0910390). And PCT patent applications are pending in Germany, Canada, Japan, and Spain.
This technology is available for licensing under either exclusive or non-exclusive terms.
Ghio AJ, Marshall BC, Diaz JL, Hasegawa T, Samuelson W, Povia D, Kennedy TP, Piantodosi CA. (1996) Tyloxapol inhibits NF-kappa B and cytokine release, scavenges HOCI, and reduces viscosity of cystic fibrosis sputum. Am J Respir Crit Care Med. 154(3 Pt 1):783-8.
Thomas Kennedy, Claude Piantadosi, Andrew Ghio
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