Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Ketone doai
Reexamination Certificate
1999-07-28
2001-11-06
Goldberg, Jerome D. (Department: 1614)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Ketone doai
Reexamination Certificate
active
06313178
ABSTRACT:
BACKGROUND OF THE INVENTION
The treatment and/or cure of cancer has been intensely investigated culminating in a wide range of therapies. Cancer has been typically treated with surgery, radiation and chemotherapy, alone or in conjunction with various therapies employing drugs, biologic agents, antibodies, and radioactive immunoconjugates, among others. The common goal of cancer treatment has been, and continues to be, the elimination or amelioration of cancerous tumors and cells with minimal unpleasant or life-threatening side effects, due to toxicity to normal tissues and cells. However, despite efforts, these goals remain largely unmet.
Even where effective non-invasive drug therapies have been developed, patients having solid malignant tumors and hematological malignant disorders often develop multidrug resistance. Current therapies involve the administration of increased dosages of the anticancer drug or drugs to which the cancer cells have become resistant and/or administration of agents designed to reverse drug accumulation defects in drug resistant cells. However, these therapies are limited by risk of toxicity to the patient.
Alpha- and beta-acids, derived from hops, possess the ability to inhibit the growth of microorganisms. Some of these acids have been used as antibiotic and antifungal agents. In addition, alpha acids (also known as humulons) have been shown to inhibit the tumor promoting effect of 12-O-tetradecanoylphorbol-13-acetate in mice (Yasukawa et al.,
Oncology
52:156-158 (1995)). Colupulone has been reported to be active against Hela cells, CEM leukemia cells, and adriamycin- and vinbiastin-resistant CEM cells (Mannering et al.,
Food, Nutrition and Chemical Toxicity
, Parke et al., eds, Smith Gordon, G. B. (1993) at ch. 28).
Thus, a need exists for new and effective drug therapies for treating cancer which have minimal side effects and are also effective against multidrug resistant cancer cells.
SUMMARY OF THE INVENTION
The present invention provides a method to inhibit cancer cell growth, and thereby to treat cancer comprising administering to a mammal afflicted with cancer an effective amount of the compound
wherein R is (C
3
-C
8
)alkyl, preferably —CH
2
CH(CH
3
)
2
, —CH(CH
3
)
2
, or —CH(CH
3
)CH
2
CH
3
, or a pharmaceutically acceptable salt thereof. In a preferred embodiment of the invention, R is —CH(CH
3
)
2
. The present invention further provides a method of inhibiting bacterial cell growth by contacting bacterial cells with an effective amount of a compound of formula (I). The present invention also provides pharmaceutical compositions, such as compositions adapted for topical administration, comprising an effective amount of a compound of formula (I) in combination with a pharmaceutically acceptable carrier. The compounds of the invention are particularly effective against gram positive bacteria, such as mycobacterium strains, including drug-resistant M. tuberculosis strains or Mycobacterial avian complex (MHC). The compounds are also active against S. aureus, including methocillin-resistant S. aureus.
As used herein, the term alkyl encompasses branched and straight-chain alkyl groups, as well as cycloalkyl and (cycloalkyl)alkyl.
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Carson, J.F., “The Hydrogenatio of Lupulone and Humulone”Journal of the American Chemical Society,73, pp. 1850-1852, (Apr. 1951).
Gomez-Flores, “Enhanced Intramacrophage Aactivity of Resorcinomycin a AgainstMycobacterium avium-Mycobacterium intracellulare Complex after Liposome Encapsulation”,Antimicrobial Agents&Chemotheraphy,40 (11), pp. 2545-2549, (Nov. 1996).
Ji, et al., “How Effective is KRM-1648 in Treatment of DisseminatedMycobacterium aviumcomplex Infections in Beige Mice?”,Antimicrobial Agents&Chemotherapy,40 (2), pp. 437-442, (Feb. 1996).
Mannering, G.J., et al., “Effects of the Hop Component, Colupulone, on the Induction of Cytochrome P4503A and the Replication of Human Tumour Cells”,Food, Nutrition and Chemical Toxicity,Chapter 28, Smith-Gordon and Company Limited, London, UK, pp. 311-323, (1993).
Mizobuchi, S., et al., “Antifungal Activities of Hop Bitter Resins and Related Compounds”,Agric. Biol. Chem.,49 (2), pp. 399-403, (1985).
Mizobuchi, S., et al., “Antifungal Activities of Hop Bitter Resins and Related Compounds”,Rep. Res. Lab. Kirin Brew. Co.,No. 28, pp. 39-44, (1985).
Yasukawa, K., 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,52, pp. 156-158, (1995).
Mannering Gilbert J.
Ngo Emily O.
Nutter Louise
Stephan Thomas
Goldberg Jerome D.
Regents of the University of Minnesota
Schwegman Lundberg Woessner & Kluth P.A.
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