Drug – bio-affecting and body treating compositions – Plant material or plant extract of undetermined constitution... – Containing or obtained from palmaceae
Reexamination Certificate
2000-04-07
2001-08-21
Tate, Christopher R. (Department: 1651)
Drug, bio-affecting and body treating compositions
Plant material or plant extract of undetermined constitution...
Containing or obtained from palmaceae
C435S067000, C435S183000, C435S189000, C514S691000, C514S724000, C585S351000
Reexamination Certificate
active
06277417
ABSTRACT:
FIELD OF THE INVENTION
This invention relates to methods of inhibiting the activity of the enzyme 5&agr;-reductase. More particularly, this invention relates to methods of inhibiting 5&agr;-reductase by administration of a composition comprising the carotenoid astaxanthin, derivable from
Haematococcus pluvialis
microalgae, to treat or prevent disorders in humans resulting from the activity of the enzyme, in particular benign prostate hyperplasia and prostate cancer.
BACKGROUND OF THE INVENTION
Enlargement of the prostate, which affects fifty percent of men aged 60 and ninety percent of men by age 85, is commonly referred to as benign prostate hyperplasia (BHP). BPH is a slow, progressive enlargement of the fibromuscular and epithelial structures of the prostate gland. The symptoms of BPH include decreased urinary flow, urinary retention, frequent urination and impotency. Substantial evidence indicates that the androgens testosterone and dihydrotestosterone (DHT) are contributing factors in producing BPH in the prostate. Tyler, V. E.,
The Honest Herbal: A sensible guide to the use of herbs and related remedies
. (Pharmaceutical Products Press, New York 1982). Testosterone is converted by 5&agr;-reductase to DHT which is about five times more potent than testosterone. DHT binds to cytoplasmic receptors in the prostate, where it initiates RNA and DNA synthesis. This action, in turn induces protein synthesis and abnormal growth of the prostate. (Tyler, V. E.,
Herbs of Choice: The therapeutic use of phytochemicals
. (Pharmaceutical Products Press, New York 1994)). Current clinical evidence indicates that inhibition of 5&agr;-reductase reverses the symptoms of BPH in human males. (Strauch, G. et al.,
Eur. Urol
., Vol. 26, pp. 247-252 (1994); Rhodes, L. et al.,
Prostate
, Vol. 22, pp. 43-51 (1993)).
There is now substantial evidence that androgen deprivation can decrease the obstructive symptoms of BPH. Further, 5&agr;-reductase activity appears to be higher in cells obtained from BPH tissue than from normal prostate tissue. (Bone, K., The European Journal of Herbal Medicine, Vol. 4(1), pp. 15-24 (1998)). Inhibitors of 5&agr;-reductase, such as the drug finasteride (PROSCAR), block the conversion of testosterone to DHT and have been found to reduce the size of the prostate leading to an increase in peak urinary flow rate and a reduction in symptoms (Strauch et al. 1994; Rhodes et al. 1993). Natural products such as the lipid extracts of Saw Palmetto berries (LESP),
Serenoa repens
, have also been found to reduce the conversion of testosterone to DHT by the inhibition of 5&agr;-reductase both in vitro and in vivo (Bone, 1998; Di Silverio, F. et al.,
Eur. Urol
., Vol. 21, pp. 309-314 (1992)).
Further, 5&agr;-reductase has also been implicated as playing a central role in the proliferation of prostate cancer. Iehlé, C. et al.,
Journal of Steroid Biochemistry and Molecular Biology
, Vol. 54, pp. 273-279 (1995) (and references cited therein). See also, Isaacs, J. T. et al.,
J. Androl
., Vol. 13 p. 457 (1992); Brinkmann, A. O. et al.,
J. Steroid Biochem. Mol. Biol
., Vol. 41, p. 361 (1992); Simental, J. A. et al.,
J. Steroid Biochem. Mol. Biol
., Vol. 43, p. 37 (1992); Ware, L. J. et al.,
Cancer Metastasis Rev
., Vol. 12, p. 287 (1993); Steiner, M. S.,
Urology
, Vol. 42, p. 99 (1993).
Astaxanthin, a red carotenoid has the following structure:
Haematococcus pluvialis
microalgae is a natural source of astaxanthin. The microalgae also contains fatty acids such as palmitic, oleic, linoleic and stearic acids, protein, minerals, carbohydrates and vitamins. As explained more fully below, the present invention comprises the discovery that when tested in a 5&agr;-reductase in vitro assay with a pre-digestion model,
Haematococcus pluvialis
algae meal containing the carotenoid astaxanthin demonstrated 98% inhibition of 5&agr;-reductase at a concentration of 300 &mgr;g/mL.
Thus, the major advantage provided by the present invention is a method of inhibiting the enzyme 5&agr;-reductase in a human subject by the administration of a composition comprising the carotenoid astaxanthin. Because of its ability to inhibit the enzyme 5&agr;-reductase, a composition comprising the carotenoid astaxanthin would therefore be useful for preventing and/or treating Benign Prostate Hyperplasia in a human subject, and preventing and/or treating prostate cancer in a human subject by administering a composition comprising astaxanthin to the subject.
These and additional objects and advantages of the present invention are shown from the description below. The disclosures of the publications cited above and throughout this specification are incorporated in their entirety to more fully describe the invention and to demonstrate the state of the art.
SUMMARY OF THE INVENTION
This invention provides a method for inhibiting the activity of the enzyme 5&agr;-reductase in a human subject which comprises administering to the subject a composition comprising the carotenoid astaxanthin.
The invention also provides a method for treating Benign Prostate Hyperplasia in a human subject which comprises administering to the subject a composition comprising the carotenoid astaxanthin.
The invention further provides a method for preventing Benign Prostate Hyperplasia in a human subject which comprises administering to the subject a composition comprising the carotenoid astaxanthin.
The invention further provides a method for treating prostate cancer in a human subject which comprises administering to the subject a composition comprising the carotenoid astaxanthin.
Finally the invention provides a method for preventing prostate cancer in a human subject which comprises administering to the subject a composition comprising the carotenoid astaxanthin.
DETAILS OF THE INVENTION
In the practice of the methods of this invention, astaxanthin is administered to a human subject in need of treatment and/or prevention of ailments caused by the activity of the enzyme 5&agr;-reductase. The enzyme 5&agr;-reductase is known to exist in two distinct isozymes, designated type 1 (displaying maximal activity at neutral-basic pH) and type 2 (displaying maximal activity at acidic pH). There is evidence for the expression of both types in the prostate. Hirsh, K. S. et al.,
Proc. Natl. Acad. Sci. USA
, Vol. 90, pp. 5277-5281 (1990); Bonnet, P. et al.,
J. Clin. Endocr. Metab
., Vol. 77, pp. 1203-1208 (1993). As used herein, the term “5&agr;-reductase”, and the ability of the compounds described herein to inhibit the activity of the enzyme “5&agr;-reductase”, is meant to encompass both type 1 and type 2. Compositions containing astaxanthin are demonstrated herein to inhibit the activity of the enzyme 5&agr;-reductase in in vitro assays that are closely predictive of the ability of such compounds to inhibit the enzyme in a human subject.
In the practice of the methods of this invention astaxanthin from any source, whether natural or synthetic, can be used. Synthetic methods for preparing astaxanthin are known (R. D. G. Cooper et al.,
J. Chem Soc. Perkins Trans. I
, (1975) p. 2195; F. Kienzle, H. Mayer,
Helv. Chim. Acta
., (1978) Vol. 61, p. 2609) as are methods of isolating astaxanthin from natural sources (Tischer,
Z. Physiol. Chem
., (1941) Vol. 267 p. 281; Seybold and Goodwin, Nature, (1959) Vol. 184, p. 1714).
Haematococcus pluvialis
microalgae is a preferred natural, commercially available source of the astaxanthin used in the methods of this invention. Thus, astaxanthin can be administered in a pure form as synthesized or isolated from natural sources. Alternatively, and as a preferred embodiment of the methods of the invention, astaxanthin is administered as part of a composition comprising protein, carbohydrate, and fatty acids. When
Haemotococcus pluvialis
algae meal is used as the source of astaxanthin, the composition is preferrably administered as derived from the microalgae, comprising the natural protein, carbohydrate, and fatty acid components of the microalgae. Such microalgae is commercially available (Cyanotech Corporation
Fitzpatrick ,Cella, Harper & Scinto
Tate Christopher R.
Triarco Industries, Inc.
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