Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Reexamination Certificate
1999-07-30
2001-02-06
Jarvis, William R. A. (Department: 1614)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
C514S457000
Reexamination Certificate
active
06184246
ABSTRACT:
BACKGROUND OF THE INVENTION
This invention relates to a method of inhibiting the production of cytokines, particularly inhibiting the production of tumor necrosis factor&agr;, interleukin-10, and macrophage inflammatory protein-1&agr;, in a mammal, including a human, in need thereof which involves administering to such mammal an effective, cytokine production inhibiting amount of a polymethoxylated flavone.
Flavonoids are widely distributed in the plant kingdom and as many as 4000 flavonoid-related compounds have been described (Brandi, M. L., Bone Miner., 1992, (Suppl. 1), S3-14). Ingested at hundreds of mg per day in the Western diet, flavonoids appear to have several beneficial effects on human health. Of particular interest are the flavonoids derived from citrus, many of which exhibit anticancer, anticarcinogenic, antiviral, antioxidant, antithrombogenic, and antiatherogenic properties (Benavente-Garcia, O., et al., J. Agr. Food Chem., 45: 4505-4515 (1997)). Polymethoxylated flavones from citrus have been shown to reduce the invasiveness of tumors in animal models (Vermeulen, S., et al., Pathology Res. Practice, 192: 694-707 (1996)) and to induce the differentiation of myeloid leukemic cells and suppress proliferation while promoting apoptosis (Sugiyama, S., et al., Chem. Pharm. Bull., 41: 714-719 (1993); Hirano, T., et al., Brit. J. Cancer, 72: 11380-1388 (1995)). These polymethoxylated flavones have further been shown to reduce lymphocyte proliferation (Mookerjee, B. K., et al., J. Immunopharmacol., 8:371-392 (1986)), platelet aggregation (Beret, A., et al., in Plant Flavonoids in Biology and Medicine II: Biochemical, Cellular, and Medicinal Properties; Cody, V., Middleton, E. Jr., Harborne, J. B., Beretz, A., Eds.; Progress in Clinical and Biological Research 280; Alan R. Liss Inc.: New York, 1988; p 187-200), and to suppress ethanol-induced gastric hemorrhagic lesions (Takase, H., et al.,. Japan. J. Pharmacol., 66: 139-147 (1994)), while promoting chloride secretion by human colonic epithelial cells (Nguyen, T. D., et al., J. Nutrition, 123: 259-268 (1993)). The antiinflammatory properties of dietary flavonoids have also received considerable attention. Select hydroxylated flavones block adhesion molecule biosynthesis by cytokine-induced endothelial cells (Baloch, Z., et al., Cell Immunol., 160: 98-103 (1995); Gerritsen, M. E., et al., Am. J. Pathol., 147: 278-292 (1995)). In other studies, flavonoids have been shown to block activation-induced degranulation of neutrophils and mast cells (Middleton, E., Jr., et al., Biochem. Pharmacol., 43: 1167-1179 (1992)). A formulation of citrus flavonoids has been shown to block capillary leakage and leukocyte infiltration in animal models (Bouskela, E., et al., Angiology, 48: 391-399 (1997); Friesenecker, B., et al.,. Int. J. Microcirc., (suppl. 1), 17-21 (1995).
Central to many aspects of inflammation are the cytokines which behave as autocrine or paracrine protein factors. In particular, the cytokine, tumor necrosis factor-&agr; (TNF&agr;), drives many critical components of inflammatory processes (Feldmann, M., et al., Annu. Rev. Immunol., 14: 397-440 (1996); Moreland, L. W., N. Engl. J. Med., 337:141-147 (1997)). Monocytes are a major cellular source of TNF&agr; and other cytokines. Recently the main flavanone glycoside in grapefruit, naringin, has been reported to suppress lipopolysaccharide-induced TNF&agr; release and liver injury in mice (Kawaguchi, K., et al., Eur. J. Pharmacol., 368: 245-250 (1999)). However, apparently there have been no reports of polymethoxylated flavonoids inhibiting the production of cytokines (e.g., tumor necrosis factor&agr;, interleukin-10, macrophage inflammatory protein-1&agr;).
SUMMARY OF THE INVENTION
This invention provides a method of inhibiting the production of cytokines, particularly inhibiting the production of tumor necrosis factor&agr;, interleukin-10, and macrophage inflammatory protein-1&agr;, in a mammal, including a human, in need thereof which involves administering to such mammal an effective amount, preferably cytokine production inhibiting amount, of a polymethoxylated flavone.
REFERENCES:
patent: H1427 (1995-04-01), Briet et al.
patent: 3867541 (1975-02-01), Robbins
patent: 3903266 (1975-09-01), Robbins
patent: 4886806 (1989-12-01), Walenta et al.
patent: 5013852 (1991-05-01), Walenta et al.
patent: 5096906 (1992-03-01), Mandell et al.
patent: 5336685 (1994-08-01), Prochaska et al.
patent: 5399584 (1995-03-01), Ares et al.
patent: 5443839 (1995-08-01), Meybeck
patent: 5547970 (1996-08-01), Weithmann et al.
patent: 5646154 (1997-07-01), Irie et al.
patent: 5658949 (1997-08-01), Aggarwal
patent: 5792448 (1998-08-01), Dubief et al.
patent: 5847123 (1998-12-01), Yokoyama et al.
patent: 5877151 (1999-03-01), Pereira
patent: 5900430 (1999-05-01), Badger et al.
patent: 5900434 (1999-05-01), Pyun et al.
Tatum, J.H., et al., “Six New Flavonoids From Citrus”,Phytochemistry,vol. 11, pp. 2283-2288, 1972.
Chen, J., et al., “Two New Polymethoxylated Flavones, a Class of Compounds with Potential Anticancer Activity, Isolated from Cold Pressed Dancy Tangerine Peel Oil Solids”,J. Agric. Food Chem.,vol. 45(2), pp. 364-368, 1997.
Middleton, E., et al., “Tumor promoter-induced basophil histamine release: effect of selected flavonids”,Biochemical Pharmacology,vol. 36(12), pp. 2048-2052, 1987.
Ballesteros, J.F., et al., “Synthesis and Pharmacological Evaluation of 2′-Hydroxychalcones and Flavones as Inhibitors of Inflammatory Mediators Generation”,J. Med. Chem.,vol. 38(14), pp. 2794-2797, 1995.
Gerritsen, M.E., et al., “Flavonoids Inhibit Cytokine-Induced Enodtheial Cell Adhesion Protein Gene Expression”,American Journal of Pathology,vol. 147(2), pp. 278-292, 1995.
Montanari, A., et al., Citrus Flavonoids: A Review of Past Biological Activity Against Disease, in: Flavonoids in the Living System, Manthey and Buslig (eds.), Plenum Press, New York, pp. 103-116, 1998.
Internet Reference,Doctor's Guide to Medical&Other News,“TNF Shown to Be a Principal Trigger of Allergic Asthma in Animal Models”, 1996.
Horowitz, R.M., et al., “Flavonoid Constituents of Citrus”, in: Citrus Science and Technology, S. Nagy, P.E. Shaw, and M.K. Veldhuis (eds.), Avi Publishing Co., Inc., Westport, Conn., vol. 1, pp. 397-426, 1977.
Nikaido, T., et al., “Inhibition of Cyclic AMP Phosphodiesterase by Flavonoids”,Medicinal Plant Research,vol. 46, pp. 162-166, 1982.
Manthey, J.A., et al., Abstract 050, “Methoxylated Citrus Flavones Suppress Cytokine Expression By Monocytes”, Abstracts of Papers—Part 2, American Chemical Society, 216th ACS National Meeting 0-8412-3627-5, Boston, MA, Aug. 23-27, 1998.
Freedman, L., et al., “Citrus Flavonoid Complex: Chemical Fractionation and Biological Activity”,Science,pp. 344-345, 1963.
Kawaguchi, K., et al., “Suppression of lipopolysaccharide-induced tumor necrosis factor-release and liver injury in mice by naringin”,European Journal of Pharmacology,vol. 368,pp. 245-250, 1999.
Manthey, J.A., et al., “Polymethoxylated Flavones Derived from Citrus Suppress Tumor Necrosis Factor-alpha Expression by Human Monocytes”,Journal of Natural Products,vol. 62(3), pp. 441-444, 1999.
Lale et al., Ability of Different Flavonoids to inhibit . . . , J. Nat. Prod., vol. 59/3, pp. 273-6, (1996).
Louis et al., Interleukin -10 controls neutrophilic . . . , Hepatology, vol. 28/6, pp. 1607-1615 (1998).
Hurme et al., Gene polymorphisms of interleukins 1 and 10 . . . , Ann. Med., vol. 30/5, pp. 469-473, (1998).
Gerritsen et al., Flavonoids inhibit cytokine-induced endothelial,,,,, Am. J. Pathol., vol. 147/2, pp. 278-292, (1995).
Panthong e tal, antiinflammatory activity of flavonoids, Phytomedicine, vol. 1/2, pp. 141-144, (1994).
Middleton et al., The effects of citrus flavonoids on . . . , Planta med., vol. 53/4., pp. 325-328, (1987).
Busse et al., Flavonoid modulation of human neutrophil function, J. Allergy Clin. Immunol., vol. 73/6., pp. 801-809, (1984).
Manthey Carl L.
Manthey John A.
Montanari Antonio
Fado John D.
Jarvis William R. A.
Kim Vickie
Silverstein M. Howard
Stover G. Byron
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