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 Title: |
US5905089:
Use of sesquiterpene lactones for treatment of severe inflammatory disorders
[ Derwent Title ]
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| Country: |
US United States of America
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| Inventor: |
Hwang, Daniel H.; Baton Rouge, LA
Fischer, Nikolaus H.; Baton Rouge, LA
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| Assignee: |
Board of Supervisors of Louisiana State University and Agricultural and Mechanical College, Baton Rouge, LA
other patents from LOUISIANA STATE UNIVERSITY (343025) (approx. 62)
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| Published / Filed: |
1999-05-18
/ 1998-04-13
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| Application Number: |
US1998000059480
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| IPC Code: |
Advanced:
A61K 31/365;
Core:
more...
IPC-7:
A61K 31//34;
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| ECLA Code: |
A61K31/365;
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| U.S. Class: |
Current:
514/468;
Original:
514/468;
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| Field of Search: |
514/468
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| Government Interest: |
The development of this invention was partially funded by the Government under grant R01 DK-41868 from the National Institute of Health and grant 93-37200-8961 from the U.S. Department of Agriculture. The Government may have certain rights in this invention.
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| Priority Number: |
| 1998-04-13 |
US1998000059480 |
| 1997-04-14 |
US1997000080224P |
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| Abstract: |
Sesquiterpene lactones are useful in suppressing the early proinflammatory cytokines, and in ameliorating septic shock and other severe inflammatory disorders. Sesquiterpene lactones with an α-methylene-γ-lactone functional group suppress the expression of the inducible cyclooxygenase-2 and proinflammatory cytokines (Interleukin-1α and β, IL-1, and tumor necrosis factor-α (TNFα)) in mammalian macrophages stimulated with lipopolysaccharide. This suppression correlated with the inhibition of protein-tyrosine phosphorylation including the mitogen-activated protein kinases.
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| Attorney, Agent or Firm: |
Davis, Bonnie J. ;
Runnels, John H. ;
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| Primary / Asst. Examiners: |
MacMillan, Keith D.;
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| Parent Case: |
The benefit of the Apr. 14, 1997 filing date of provisional application 60/080,224 (which was a conversion of nonprovisional application 08/839,514), now abandoned, is claimed under 35 U.S.C. § 119(e).
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| Family: |
None
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First Claim:
Show all 24 claims |
We claim:
1. A method of ameliorating or preventing, in a mammal, the symptoms of a severe inflammatory disorder that is associated with the production of an agent selected from the group consisting of endotoxin, protein-tyrosine kinase, cyclooxygenase-2, tumor necrosis factor alpha, interleukin-1, interleukin-6, macrophage chemotactic protein, inducible nitric oxide synthetase, mitogen-activated protein kinase, macrophage inflammatory protein, interferon-gamma, tissue factor, granulocyte-macrophage-colony stimulating factor, and phosphotyrosine phosphatase; said method comprising administering to the mammal a therapeutically effective amount of an active sesquiterpene lactone, or a pharmaceutically acceptable salt of an active sesquiterpene lactone; wherein said active sesquiterpene lactone contains an α-methylene-γ-lactone functional group.
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| Background / Summary: |
Show background / summary
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| Drawing Descriptions: |
Show drawing descriptions
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| Description: |
Show description
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| Forward References: |
Show 12 U.S. patent(s) that reference this one
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| Foreign References: |
None
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| Other Abstract Info: |
CHEMABS 130(25)332886T
CHEMABS 130(25)332886T
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| Other References: |
U.S. application No. 08/394,148, Feng et al., filed Feb. 24, 1995.
I. Hall et al., "Anti-Inflammatory Activity of Sesquiterpene Lactones and Related Compounds," J. Pharm. Sci., vol. 68, pp. 537-542 (1979).
(6 pages)
Cited by 2 patents
I. Hall et al., "Mode of Action of Sesquiterpene Lactones as Anti-Inflammatory Agents," J. Pharm. Sci., vol. 69, pp. 537-543 (1980).
(7 pages)
Cited by 3 patents
K. Lee, "Antitumor Agents. 32. Synthesis and Antitumor Activity of Cyclopentenone Derivatives Related to Helenalin," J. Med. Chem., vol. 21, pp. 819-822 (1978).
(4 pages)
Cited by 4 patents
K. Lee et al., "Cytotoxicity of Sesquiterpene Lactones," Cancer Research, vol. 31, pp. 1649-1654 (1971).
J. Cassady, "Potential Antitumor Agents. Synthesis, Reactivity, and Cytotoxicity of α-Methylene Carbonyl Compounds," J. Med. Chem., vol. 21, pp. 815-819 (1978).
(5 pages)
Cited by 3 patents
G. Howie et al., "Potential Antitumor Agents. Synthesis of Bifunctional α-Methylene-γ-butyrolactones," J. Med. Chem., vol. 19, pp. 309-313 (1976).
(5 pages)
Cited by 4 patents
S. Kupchan, "Tumor Inhibitors. 69. Structure-Cytotoxicity Relationships among the Sesquiterpene Lactones," J. Med. Chem., vol. 14, pp. 1147-1152 (1971).
T. Waddell et al., "Antitumor Agents: Structure-Activity Relationships in Tenulin Series," J. Pharm. Sci., vol. 68, pp. 715-718 (1979).
(4 pages)
Cited by 4 patents
R. Stone, "Search for Sepsis Drugs Goes On Despite Past Failures," Science, vol. 264, pp. 365-367 (1994).
(3 pages)
Cited by 4 patents
[ISI abstract]
A. Fein, "Treatment of Severe Systemic Inflammatory Response Syndrome and Sepsis with a Novel Bradykinin Antagonist, Deltibant (CP-0127)," J. Am. Med. Assoc., vol. 277, pp. 482-487 (1997).
(6 pages)
[ISI abstract]
P. Chanmugam, "Radicicol, a Protein Tyrosine Kinase Inhibitor, Suppresses the Expression of Mitogen-Inducible Cyclooxygenase in Macrophages Stimulated with Lipopolysaccharide and in Experimental Glomerulonephritis," J. Biol. Chem., vol. 270, pp. 5418-5426 (1995).
(9 pages)
Cited by 5 patents
[ISI abstract]
A. Novogrodsky et al., "Prevention of Lipopolysaccharide-Induced Lethal Toxicity by Tyrosine Kinase Inhibitors," Science, vol. 264, pp. 1319-1322 (1994).
(4 pages)
Cited by 9 patents
[ISI abstract]
T. Akiyama et al., "Genistein, a Specific Inhibitor of Tyrosine-Specific Protein Kinases," Journal of Biological Chemistry, vol. 262, pp. 5592-5595 (1986).
Hwang et al., "Inhibition of the Expression of Inducible Cyclooxygenase and Proinflammatory Cytokines by Sesquiterpene Lactones in Macrophages Correlates with the Inhibition of MAP Kinases," Biochem. and Biophys. Res. Comm., vol. 226, pp. 810-818 (1996).
(9 pages)
Cited by 3 patents
[ISI abstract]
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