Bioactive compositions derived from humulus lupulus

Drug – bio-affecting and body treating compositions – Plant material or plant extract of undetermined constitution...

Reexamination Certificate

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Reexamination Certificate

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07144590

ABSTRACT:
Disclosed is a novel anti-inflammatory pharmaceutical composition that exhibits potent and selective inhibition of the cycloooxygenase-2 (COX-2) enzyme. The formulation consists of a hops extract that exhibits COX-2 selectivity as defined by dividing the IC50 COX-2/IC50COX-1 concentrations that are determined by testing with the William Harvey Whole Blood Assay (WHMA), and falls in the range of 0.011 to 0.2. Such compositions may also optionally contain high levels of alpha acids and low levels of beta acids, some flavonoid compounds, and virtually no essential oils. Such compositions are useful for treating conditions that manifest as inflammatory pain, or are impacted by the COX-2 enzyme. The recited compositions are particularly beneficial for treating osteoarthritis and rheumatoid arthritis, and can be used for chronic pain with reduced gastric side-effects.

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Wolfe M. Michael, M.D. et al. “Gastrointestinal Toxicity of Nonsteroidal Antinflammatory Drugs”, New England Journal of Medicine, vol. 340, No. 24, pp. 1888-1899, Jun. 17, 1999.
Brooks P. et al. “Interpreting the clinical significance of the differential inhibition of cyclooxygenase-1 and cyclooxygenase-2”, British Society for Rheumatology, vol. 38, pp. 779-788, 1999.
Warner Timothy D. et al. “Nonsteroid drug selectivities for cyclo-oxygenase-1 rather than cyclo-oxygenase-2 are associated with human gastrointestinal toxicity: A full in vitro analysis”, Proc. Natl. Acad. Sci. USA, vol. 96, pp. 7563-7568, Jun. 1999.
Yasukawa Ken et al. “Humulon, a Bitter in the Hop, Inhibits Tumor Promotion by 12-0-Tetradecanoylphorbol-13-Acetate in Two-Stage Carcinogenesis in Mouse Skin”, Oncology, vol. 52, pp. 156-158, 1995.
Yamamoto Kei et al. “Suppression of cyclooxygenase-2 gene transcription by humulon of beer hop extract studied with reference to glucocorticoid”, Federation of European Biochemical Societies, vol. 465, pp. 103-106, 2000.
Wallace J.L. et al., “NSAID-Induced Gastric Damage in the rat: Requirement for Inhibition of Both Cyclooxygenase-1 and Cyclooxygenase-2”, Gastroenterology, vol. 119, pp. 706-714, 2000.

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