Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Reexamination Certificate
1999-08-02
2003-09-02
Travers, Russell (Department: 1617)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
C514S419000
Reexamination Certificate
active
06613792
ABSTRACT:
TECHNICAL FIELD
This invention relates to the use of various naturally occurring compounds to treat the symptoms of diseases, and, more particularly, to the use of the natural product indole-3-methanol and related compounds to alleviate the symptoms associated with premenstrual syndrome and menopause.
BACKGROUND
Premenstrual syndrome (“PMS”), a chronic complaint of a substantial percentage of women between the ages of 12 and 50, manifests in symptoms before and during menses. The symptoms include pain, marked general tension, marked irritability, anxiety, depression, abdominal bloating, swelling of subcutaneous tissues, nausea, fatigue, painful swelling of the breasts, headaches, dizziness, and palpitations. J. T. E. Richardson, “The Menstrual Cycle, Cognition, and Paramenstrual Symptomatology”,
Cognition and the Menstrual Cycle
(Springer-Verlag 1992). While virtually all women experience pain at the onset of menstruation, many women also experience some of the listed symptoms several days before the onset of menses. The symptoms vary from one menstrual cycle to another, and vary considerably among individual women. These symptoms are generally conceded to be related to the release of various hormones, including estrogens.
For women who experience severe PMS, there is considerable desire for their pain and suffering to be relieved. Some women find that their cognitive abilities are impaired and hope for ways to improve their cognitive performance during the days when affected by PMS. Id.
Studies have revealed that during PMS, some women develop “food cravings” which adversely affect some aspects of their health. J. J. Rapkin & D. Tonnesses,
A Woman Doctor's Guide to PMS
, (Hyperion, 1994). Generally, these patients are directed to eat regular small meals, decrease their intake of salt, fat, sugar, and caffeine, and increase consumption of whole grains, seed and nuts, vegetables, fruits, and vegetable oils. In addition, vitamins and dietary supplements such as primrose oil are sometimes used by women to alleviate the symptoms of PMS.
Menopause, or “the change of life”, occurs when a woman's cycle of ovulation and menses ends. Common symptoms of menopause include hot flashes, excessive sweating, vaginal atrophy, and sleep disturbances. Menopause is a natural consequence of aging caused when a woman's ovaries begin to produce less estrogen. It is widely accepted that the symptoms of menopause result from decreased estrogen in the body. I. Schiff,
Menopause
(Times Books, a division of Random House, 1996). It is often acknowledged that the manifestations of menopause can be alleviated by controlling the diet. For example, it has been observed that women in Japan and China have decreased menopausal severity compared to women in Western countries. In most texts, this is attributed to the consumption of soy products. However, it must be recognized that Asian women also eat substantial amounts of cruciferous vegetables in addition to soy products. The possibility that menopausal symptoms result from changes in estrogen metabolism is seldom mentioned.
Beginning in the 1960's, many symptoms of menopause have been dealt with through estrogen supplementation. B. Kass-Annese,
Management of the Perimenopausal
&
Postmenopausal Woman
(Lippincott, 1999). More recently, other hormones, such as progesterone, have been employed. Other steroids have been suggested, along with numerous medications, to relieve various symptoms. While many studies have investigated the various hormones which might be taken by various means, little research has been done to investigate the ways in which hormones, particularly estrogens, might be metabolized to alter their physiological effects. 1H-indole-3-methanol (CAS Registry Number [700-06-1]) is a naturally occurring product which is derived from cruciferous vegetables. It is known to exhibit substantial effects in the metabolism of estradiol as reported by many workers, and has been implicated as having potential utility in the treatment of breast cancer. In this regard, one of 1H-indole-3-methanol's pharmacological activities is that of an estradiol 2-hydroxylase inducer. Some of its effects have been summarized in a review by Michnovicz and co-workers. Michnovicz et al. “Changes in Levels of Urinary Estrogen Metabolites After Oral Indole-3-Carbinol Treatment in Humans”, J.
Nat'l Cancer Inst.
, 89(10):718-23 (1997). It has also been observed that 1H-indole-3-methanol reacts with itself in stomach acid and under other conditions such as heat, light and even water solutions to form new compounds (“1H-indole-3-methanol compounds”). See, e.g., Michnovicz & Bradlow, “Dietary Cytochrome P-450 Modifiers in the Control of Estrogen Metabolism”,
Food Phytochemicals for Cancer Prevention I, Fruits
&
Vegetables
, pp. 282-293, nn. 89-93, edited by Mou-Tuan et al. ACS Symposium Series 546 (American Chemical Society, Washington, D.C., 1994). Some of these 1H-indole-3-methanol compounds (e.g., diindolylmethane and indolo(3,2-b)carbazole) are reported to bind the same receptors as the 1H-indole-3-methanol. Id.
Although described for the potential treatment of breast cancer and fibromyalgia (see, e.g., U.S. Pat. No. 5,895,787 to Arffmann et al. (Apr. 20, 1999), heretofore, the use of 1H-indole-3-methanol compounds for treating conditions such as PMS and hormone related difficulties associated with menopause is not believed to have been described.
DISCLOSURE OF THE INVENTION
Dietary indoles, particularly, 1H-indole-3-methanol, have been found to greatly relieve the symptoms of premenstrual syndrome (PMS) and menopause. Patients with PMS have reported decreased menstrual cramping, decreased menstrual flow, shorter duration of menses, decreased fatigue, less frequent headaches, improved mood, and decreased bloating resulting from the oral administration of pharmaceutically effective amounts of dietary indoles derived from 1H-indole-3-methanol. Positive results were sometimes seen within one menstrual cycle of using daily doses of 1H-indole-3-methanol compounds. Patients suffering from menopause have reported considerable reductions in hot flashes and sweating profusion and less sleep disturbances resulting from the oral administration of pharmaceutically effective amounts of dietary indoles derived from 1H-indole-3-methanol.
The invention thus includes a method of treating PMS in a patient believed to be suffering therefrom, the method comprising: administering to the patient an 1H-indole-3-methanol compound in a medically acceptable manner in a pharmaceutically effective amount on a daily basis or during a specific portion of the menstrual cycle, such as days 7-21 after menses.
The invention also includes a method of treating menopause in a patient believed to be suffering therefrom, the method comprising: administering to the patient an 1H-indole-3-methanol compound in a medically acceptable manner in a pharmaceutically effective amount on a daily basis.
The invention also includes methods of making a pharmaceutical compositions containing an 1H-indole-3-methanol compound or compounds for use in the treatment of menopause or PMS.
BEST MODE FOR CARRYING OUT THE INVENTION
1H-indole-3-methanol compounds are naturally occurring compounds. These dietary indoles result from the maceration of cruciferous vegetables by the manner briefly described herein. Glucosinolates, a set of compounds containing a glucose component, a sulfur-carbon-nitrogen component, and a variable component, occur in varying ratios in varietals, leaves, stocks, stems, flowers, seeds, and roots of the brassica (or crucifiers) plants. For example, in glucobrassicin, a glucosinolate, the variable component is 3-indolylmethyl. When the cell walls of the plant are destroyed through chopping, grinding, chewing, for example, an enzyme, myrosinase, is released. Myrosinase aids in the hydrolysis of glucobrassicin resulting in the release of 1H-indole-3-methanol, often called indole-3-carbinol. 1H-indole-
3
-methanol is produced in sufficient quantity that it can be isolat
Andrus G. Merrill
Ellenberger Suzanne R.
Ellenberger William P.
Designed Nutritional Products, Inc.
Travers Russell
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