Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Reexamination Certificate
2000-09-20
2002-02-26
Goldberg, Jerome D. (Department: 1614)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
C514S762000
Reexamination Certificate
active
06350776
ABSTRACT:
1. INTRODUCTION
The present application relates to methods of treating or preventing proliferative disease, particularly cancer, by administering to a subject a composition comprising lycopene and alpha-tocopherol.
2. BACKGROUND OF THE INVENTION
Lycopene, a natural red carotenoid found in nature in high amounts in tomatoes and also in tomato-derived products, is a potent antioxidant and free radical quencher. Lycopene has been found concentrated in various body tissues, such as liver, adrenal, and adipose tissues, as well as in the prostate. In vitro studies have shown that lycopene has a growth inhibitory effect on mammary, lung, and endometrial carcinoma cell proliferation at and an inhibitory effect on prostate carcinoma cell proliferation at concentrations of 50 &mgr;M and above. Little physiological significance can be attributed to the latter finding as the inhibitory concentrations in vitro far exceeded typical physiological plasma concentrations for lycopene. Epidemiological studies have associated lycopene intake with a decreased risk of prostate cancer.
Tocopherol compounds, also called vitamin E, are active components in vegetable oils. Vitamin E activity refers to the physiological activity of this group of nutrient materials. Materials having a vitamin E activity all belong to a distinct series of compounds which are all derivatives of chroman-6-ol. These compounds are all tocol derivatives having an isoprenoid C16-sidechain. The term “tocol” is used to mean 2-methyl-2-(4′,8′,12′-trimethyltridecyl) chroman-6-ol. These compounds are alpha-, beta-, gamma-, and delta-tocopherol, and are of primary importance for vitamin E activity.
Alpha-tocopherol is produced commercially for use as a feed supplement for domestic animals as a source of Vitamin E activity and as a nutrient supplement for humans. Tocopherols are also used in food technology as an antioxidant to retard the development of rancidity in fatty materials. The tocopherols are found widely distributed in normal foods, occurring in the highest concentration in the cereal grain oils, principally in corn and wheat oils, but also in barley and rye oils. They are also found in other vegetable oils such as safflower, soybean, peanut, cottonseed, linseed, sunflower, rapeseed and palm, and in other vegetable sources, e.g., palm leaves, lettuce, alfalfa, rubber latex and a variety of other plant materials. The proportion of the most active form, the D-alpha-tocopherol, varies widely among the different sources. Two sources having the highest levels of D-alpha-tocopherol are safflower oil and sunflower oil, although the most commonly available source is soybean oil, which has a considerably lower percent of D-alpha-tocopherol than safflower and sunflower oils, and with significantly higher percentages of the gamma- and delta-homologues. In addition to being a source for tocopherol homologues, palm oil, oats, rye, and barley also contain tocotrienol.
Of the tocopherols, alpha-tocopherol has the highest vitamin E activity and is the most valuable. Biochemical studies have shown that alpha-tocopherol inhibits cell proliferation in certain sensitive cell lines. Epidemiological studies also have associated alpha-tocopherol intake with a decreased risk of prostate cancer.
3. SUMMARY OF THE INVENTION
The present invention is based upon the discovery that lycopene and alpha-tocopherol synergize to inhibit cancer cell proliferation, that is, the combination of lycopene and alpha-tocopherol inhibits cancer cell proliferation to a greater extent than the additive inhibitory effects of lycopene and alpha-tocopherol alone on cancer cell proliferation.
Accordingly, the present invention provides methods of treating or preventing proliferative disease, particularly cancer, in a subject in need thereof, preferably a human subject, by administration of a composition comprising both lycopene and alpha-tocopherol. The composition containing lycopene and alpha-tocopherol is preferably administered so as to result in plasma levels of 0.01 to 5.0 &mgr;M lycopene and 1 to 100 4&mgr;M alpha-tocopherol.
REFERENCES:
patent: 7400862 (1975-07-01), None
patent: WO 96/19215 (1996-06-01), None
patent: WO 96/19217 (1996-06-01), None
Wang et al, J. Cell. Biochem., 62(1), pp 19-26 Abstract Only, 1996.*
Sharoni et al, Spec. Publ.-R. Soc. Chem., pp 378-385, Abstract Only 1996.*
Giovannucci and Clinton, 1998, “Tomatoes, lycopene, and prostate cancer”, Proc. Soc. Exp. Biol. Med. 218(2):129-39.
Heinonen et al., 1998, “Prostate cancer and supplementation with alpha-tocopherol and beta-carotene: incidence and mortality in a controlled trial”, J. Natl. Cancer. Inst. 90(6):440-6.
Pastori et al., 1998, “Lycopene in association with &agr;-tocopherol inhibits at physiological concentrations proliferation of prostate carcinoma cells”, Biochem. Biophys. Res. Comm. 250:582-5.
Sharoni and Levy, 1996, “Anticarcinogenic properties of lycopene”, Spec. Publ. R Soc. Chem. 181:378-85.
Sigounas et al., 1997, “dl-&agr;-tocopherol induces apoptosis in erythroleukemia, prostate, and breast cancer cells”, Nutr. Cancer 28(1):30-5.
Tasinato et al., 1995, “D-alpha-tocopherol inhibition of vascular smooth muscle cell proliferation occurs at physiological concentrations, correlates with protein kinase C inhibition, and is independent of its antioxidant properties”, Proc. Natl. Acad. Sci. 92(26):12190-4.
Upston et al., 1999, “Tocopherol-mediated peroxidation of lipoproteins: implications for vitamin E as a potential antiatherogenic supplement”, FASEB J. 13(9):977-94.
Wang et al., 1996, “Reproducibility of erythocyte polyamine measurements and correlation with plasma micronutrients in an antioxidant vitamin intervention study”, J. Cell. Biochem. 62(1):19-26.
Goldberg Jerome D.
Pennie & Edmonds LLP
LandOfFree
Method of treating proliferative disease with lycopene and... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Method of treating proliferative disease with lycopene and..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Method of treating proliferative disease with lycopene and... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2973947