Note: Descriptions are shown in the official language in which they were submitted.
CA 02492417 2000-08-28
FORMULATION FOR MENOPAUSAL WOMEN
BACKGROUND OF THE INVENTION
Field of the Invention
The present invention is directed to novel
compositions for use by premenopausal women and
menopausal women for the purpose of providing improved
nutritional support and/or relief from the symptoms of
menopause, as well as to methods for using same.
Description of the Related Art
Menopause, the transition from the reproductive
stage to the non-reproductive stage of a woman's life, is
characterized primarily by the cessation of menstruation.
However, menopause has come to signify much more than
simply the loss of reproductive capability, as it is also
associated with a number of acute and chronic conditions.
Menopausal syndrome consists of a number of varying and
often highly distressing symptoms resulting from hormonal
imbalance and.nutritional deficiency in the female body.
Hot flashes and sweating secondary to vasomotor
instability affect 75% of women. Psychologic and
emotional symptoms of fatigue, insomnia, irritability and
nervousness are common. Lack of sleep due to disturbance
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by recurring hot flashes contributes to fatigue and
irritability. Dizziness, parenthesis and cardiac
symptoms o.f palpitations and tachycardia may also occur;
the incidence of heart disease increases. Other common
symptoms include nausea, constipation, diarrhea,
arthralgia and myalgia. The Merck Manual, 1793 (16t''Ed.
1992).
Menopause is also characterized by osteoporosis, or
loss of bone density, resulting in increased bone
fractures and vertebral column collapse. Bone loss
begins around age 35. This loss accelerates during
menopause, which generally occurs around age 45 to 55.
Bone mass losses average 1-2% each year after menopause.
Primary sites are the vertebrae, which show anterior
collapse resulting in stooping and backache, the hips and
the wrist. The Merck Manual 1793(16th Ed. 1992).
Osteoporosis develops over decades and is related to peak
bone mass, as well as to the degree of bone loss.
Estrogen replacement therapy has been used to
relieve the symptoms of menopause. The Merck Manual
1793(16th Ed. 1992). However, estrogen therapy is not
without its limitations. In some instances the side
effects of estrogen therapy can be quite severe. These
side effects include increased risk of certain cancers,
such as breast cancer. Estrogen has also been implicated
in certain endometrial cancers. Although treatments with
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progestin have been shown to counter these adverse side
effects, postmenopausal women treated with such an
estrogen-progestin regimen frequently experience
undesirable uterine bleeding. Further, hormone therapy
alone is insufficient to meet the varied and heightened
nutritional requirements of a woman during this phase in
her life. Adequate nutritional intake is also necessary.
Appropriate nutritional intake is increasingly
important to menopausal women. For example, adequate
calcium intake prevents osteoporosis. Moreover, certain
vitamins and minerals enhance calcium absorption and
utilization. However, while vitamin and mineral
supplements providing calcium for women is known in the
art, conventional supplements fail to meet other
nutritional requirements of menopausal women.
Specifically, conventional supplements lack certain fatty
acids which are especially useful to treat symptoms of
fatigue or tiredness commonly experienced by a woman
undergoing menopause. Fatty acids are essential in
supporting life's activities as the body derives most of
its energy from triglycerides, a molecule of glycerol
with three fatty acids. Linoleic acid and linolenic
acid, in particular, are two fatty acids which are
indispensable to body functions. The inclusion of these
two fatty acids in nutritional supplements is of
particular significance because they are not produced by
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the body and must be supplied through food. However,
conventional nutritional supplements fail to include
these two fatty acids.
The use of fatty acids in various forms and for
various purposes has been previously disclosed. Horrobin
et al. disclose a method of prevention or treatment of
endometriosis wherein effective amounts of one or both
gamma-linolenic acid and/or dihomo-gamma-linolenic acid
are administered to women. Specifically, the fatty acids
may be administered in the form of the acid itself or as
an ester, amide, salt or any other functional derivative
capable of being converted to the acid within the body
and may be from natural or synthetic sources.
Maxson et al., U.S. Patent No. 4,900,734, disclose
a pharmaceutical composition containing estradiol and
progesterone for oral administration. Specifically, the
pharmaceutical composition comprises estradiol dissolved
in an oil vehicle containing a suspension of micronized
progesterone. Further, the oil vehicle is high in
glycerides of polyunsaturated fatty acids. Specifically,
linoleic and linolenic acids are disclosed as
particularly effective polyunsaturated fatty acids. The
combined administration of these steroids is disclosed as
being useful for replacement hormone therapy in the
treatment of menopausal women.
Cohen, U.S. Patent No. 4,945,103, discloses a method
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for treating women who suffer from premenstrual syndrome
(PMS) which comprises administration of melatonin in
sufficient doses to relieve symptoms associated with PMS.
Specifically, Cohen discloses that progestogen can be
administered in combination with melatonin. Further,
melatonin can be administered to women orally,
parenterally or in the form of an implant. Cohen
specifically discloses that PMS may be linked to a
nutritional deficiency in either vitamin B-complex,
especially vitamin B6 (pyroxidine), or essential fatty
acids, especially linolenic acid.
Horrobin, U.S. Patent No. 5,380,757, discloses a
method of treatment of vulvar dystrophy and/or vaginal
dryness, which medicament comprises gamma-linolenic (GIA)
and/or dihomo-gamma-linolenic acid (DGIA), optionally in
association with other essential fatty acids of the n-6
or n-3 series. Horrobin discloses that deficiency of
linoleic acid in the diet may produce atrophy and
hyperkeratosis of the skin.
Miyamoto et al., U.S. Patent No. 5,461,170,
disclose a glyceride preparation having a branched
saturated fatty acid and/or myristic acid residues for
use in liquid oils and/or solid cosmetics of the same.
Specifically, Miyamoto et al. disclose a polyol fatty-
acid ester having mixed acid group produced by reacting
a partial ester of a polyol and a branched fatty acid
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with a straight chain fatty acid or a lower alcohol ester
thereof in the presence of a lipase. The obtained
glyceride mixture contains a large amount of diglyceride
having a branched, saturated fatty acid group and a
straight chain, fatty acid group. The reference does not
specifically disclose either linoleic or linolenic acid
and/or menopause.
Sultenfuss, U.S. Patent No. 5,514,382, discloses a
daily vitamin and mineral supplement for women comprising
vitamin A, beta-carotene, niacin, riboflavin, pantothenic
acid, pyridoxine, cyanocobalamin, biotin,
paraaminobenzoic acid, inositol, choline, calcium,
chromium, copper, iodine, iron, magnesium, manganese,
molybdenum, selenium, zinc, and bioflavonoid. For women
over 40 years of age, iron is optionally included.
Shylankevich, U.S. Patent No. 5,569,459, discloses
compositions containing various vitamins, minerals and
herbal extracts that can be used for alleviation of
premenstrual syndrome, menopausal disorders, and
stimulating estrogen production. Specifically, the
invention relates to such pharmaceutical compositions and
dietary supplements that contain natural soybean
phytoestrogens of the isoflavone group.
Vitamins For Women disclose a
Calcium/Vitamin/Mineral supplement program for women over
forty. Specifically, the "over forty" formula discloses
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a composition containing ingredients which come in day
and/or night formulas that "assure better utilization and
absorption." Physicians's Desk Reference for
Nonprescription Drugs, ( 9'" Ed., 1988) 718.
However, the previously disclosed formulations are
deficient for various reasons. In particular, none of
the previously disclosed formulations contain critical
components, such as essential fatty acids or calcium, in
amounts specifically tailored to meet the needs of
premenopausal and menopausal women. Moreover, the
previously disclosed formulations fail to disclose the
significance of the proportion of the various components
to one another. Therefore, there is a need for
formulations specifically tailored to meet the needs of
menopausal women. Further, there is a need for drug
delivery regimens which are specifically adapted to meet
the needs of premenopausal and menopausal women.
SUMMARY OF THE INVENTION
The compositions of the present inventive subject
matter overcome the deficiencies of currently-available
nutritional supplements byproviding formulations and
drug delivery regimens which.are specifically tailored
for women just prior to, during and after the period of
menopause. The present compositions contain a novel
combination of various components, such as fatty acids,
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in critical ratios and amounts, optionally in combination
with various vitamins and minerals.
One embodiment of the present inventive subject
matter is a composition for administration to a
menopausal woman, which comprises:
an essential fatty acid compound selected from the
group consisting of a linoleic acid compound, a linolenic
acid compound, a docosahexaenoic acid compound, an omega-
3 fatty acid compound, an omega-2 fatty acid compound, a
derivative thereof and a combination thereof in an amount
of about 10 mg to about 1,000 mg;
a calcium compound or derivative thereof in an
amount of about 400 mg to about 2500 mg;
a folic acid compound or derivative thereof in an
amount of about 0.4 mg to about 5.0 mg; and
wherein the weight ratio of the essential fatt.y acid
compound to the calcium compound or derivative thereof is
about 1:0.4 to 250 in a single or multiple dosage unit.
Another embodiment of the present inventive subject
matter is a composition for administration to a
menopausal woman, which comprises:
a first fatty acid compound selected from the group
consisting of a linoleic acid compound, a derivative
thereof and a combination thereof in an amount of about
10 mg to about 1,000 mg;
a second fatty acid compound selected from the group
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consisting of a linolenic acid compound, a derivative
thereof and combinations thereof in an amount of about 10
mg to abQut 1,000 mg;
a third fatty acid compound selected from the group
consisting of a docosahexaenoic acid compound, an omega-3
fatty acid, an omega-2 fatty acid, a derivative thereof
and a combination thereof in an amount of about 10 mg to
about 1,000 mg;
a calcium compound or derivative thereof in an
amount of about 400 mg to about 2500 mg;
a folic acid compound or derivative thereof in an
amount of about 0.4 mg to about 5.0 mg;
wherein the weight ratio of the sum of the amounts
of said first and second fatty acid compounds to the
amount of said third fatty acid compound is about 1:0.5
to 1.5; and
wherein the weight ratio of the sum of the amounts
of said-first, second and third fatty acid compounds to
the amount of said calcium compound or derivative thereof
is about 1:0.4 to 50.
A further embodiment of the present inventive
subject matter is a composition for administration to a
menopausal woman, which comprises:
a first fatty acid compound selected from the group
consisting of a linoleic acid compound, a derivative
thereof and a combination thereof in an amount of about
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mg to about 1,000 mg;
a second fatty acid compound selected from the group
consisting of a linolenic acid compound, a derivative
thereof and combinations thereof in an amount of about 10
5 mg to about 1,000 mg;
a third fatty acid compound selected from the group
consisting of a docosahexaenoic acid compound, an omega-3
fatty acid, an omega-2 fatty acid, a derivative thereof
and a combination thereof in an amount of about 10 mg to
10 about 1,000 mg;
a calcium compound or derivative thereof in an
amount of about 400 mg to about 2500 mg;
a folic acid compound or derivative thereof in an
amount of about 0.4 mg to about 5.0 mg;
a vitamin C compound or derivative thereof in an
amount of about 25 mg to about 500 mg;
a vitamin E compound or derivative thereof in an
amount of about 10 mg to about 500 mg;
wherein the weight ratio of the sum of the amounts
of said first and second fatty acid compounds to the
amount of said third.fatty acid compound is about 1:0.5
to 1.5; and
wherein the weight ratio of the sum of the amounts
of said first, second and third fatty acid compounds to
the amount of said calcium compound or derivative thereof
is about 1:0.4 to 50.
CA 02492417 2000-08-28
An even further embodiment of the present inventive
subject matter is a composition for administration to a
menopausal woman, which comprises:
a first fatty acid compound selected from the group
consisting of a linoleic acid compound, a derivative
thereof and a combination thereof in an amount of about
.10 mg to about 1,000 mg;
a second fatty acid compound selected from the group
consisting of a linolenic acid compound, a derivative
thereof and combinations thereof in an amount of about 10
mg to about 1,000 mg;
a third fatty acid compound selected from the group
consisting of a docosahexaenoic acid compound, an omega-3
fatty acid, an omega-2 fatty acid, a derivative thereof
and a combination thereof in an amount of about 10 mg to
about 1,000 mg;
a calcium compound or derivative thereof in an
amount of about 400 mg to about 2500 mg;
a folic acid compound or derivative thereof in an
amount of about 0.4 mg to about 5.0 mg;
a vitamin C compound or derivative thereof in an
amount of about 25 mg to about 500 mg;
a vitamin E compound or derivative thereof in an
amount of about 10 mg to about 500 mg;
a vitamin A compound or derivative thereof in an
amount of about 2,500 IU to about 6,500 IU;
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wherein the weight ratio of the sum of the amounts
of said first and second fatty acid compounds to the
amount of said third fatty acid compound is about 1:0.5
to 1.5; and
wherein the weight ratio of the sum of said first,
second and third fatty acid compounds to the amount of
said calcium compound or derivative thereof is about
1:0.4 to 50.
Another embodiment of the present inventive subject
matter is a composition for administration to a
menopausal woman, which comprises:
a first fatty acid compound selected from the group
consisting of a linoleic acid compound, a derivative
thereof and a combination thereof in an amount of about
10 mg to about 1,000 mg;
a second fatty acid compound selected from the group
consisting of a linolenic acid compound, a derivative
thereof and combinations thereof in an amount of about 10
mg to about 1,000 mg;
210 a third fatty acid compound selected from the group
consisting of a docosahexaenoic acid compound, an omega-3
fatty acid, an omega-2 fatty acid, a derivative thereof
and a combination thereof in an amount of about 10 mg to
about 1,000 mg;
a calcium compound or derivative thereof in an
amount of about 400 mg to about 2500 mg;
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a folic acid compound or derivative thereof in an
amount of about 0.4 mg to about 5.0 mg;
a vitamin C compound or ester derivative thereof in
an amount of about 25 mg to about 500 mg;
a vitamin E compound or derivative thereof in an
amount of about 10 mg to about 500 mg;
a vitamin B6 compound or derivative thereof in an
amount of about 10 mg to about 50 mg;
a vitamin B12 compound or derivative thereof in an
amount of about 25 mcg to about 75 mcg;
a vitamin D compound or derivative thereof in an
amount of about 200 IU to about 625 IU;
wherein the weight ratio of the sum of the amounts
of said first and second fatty acid compounds to the
.15 amount of said third fatty acid compound is about 1:0.5
to 1.5; and
wherein the weight ratio of the sum of the amounts
of said first, second and third fatty acid compounds to
the amount of said calcium compound or derivative thereof
is about 1:0.4 to 50.
Yet another embodiment of the present inventive
subject matter is a composition for administration to a
menopausal woman, which comprises:
a biologically active substance for treating
symptoms of menopause;
a calcium compound or derivative thereof in an
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amount of about 400 mg to about 2500 mg;
a folic acid compound or derivative thereof in an
amount of about0.4 mg to about 5.0 mg.
A further embodiment of the present inventive
subject matter is a drug delivery regimen, which
comprises:
a first dosage form comprising a first biologically
active substance to be administered to a menopausal woman
at a predetermined time period;
a second dosage form comprising a second
biologically active substance to be administered to the
menopausal woman simultaneously with said first dosage
form;
wherein said first biologically active substance
and said second biologically active substance are
incompatible substances.
An additional embodiment of the present inventive
subject matter is a method for providing nutritional
supplementation to a menopausal woman, which comprises:
administering an essential fatty acid compound to
the woman during the period commencing at the onset of
menopause, said essential fatty acid compound being
selected from the group consisting of a linoleic acid
compound, a linolenic acid compound, a docosahexaenoic
acid compound, an omega-3 fatty acid compound, an omega-2
fatty acid compound, a derivative thereof and a
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combination thereof;
administering about 400 mg to about 2500 mg of a
calcium compound or derivative thereof to the woman
during the period commencing at the onset of menopause;
administering about 0.4 mg to about 5.0 mg of a
folic acid compound or derivative thereof to the woman
during the period commencing at the onset of menopause;
and
wherein the weight ratio of the essential fatty acid
compound to the calcium compound or derivative thereof is
about 1:0.4 to 250.
Another embodiment of the present inventive.subject
matter is a method for providing nutritional
supplementation to a menopausal woman, which comprises:
administering a first fatty acid compound to the
woman during a period commencing at the onset of
menopause, said first fatty acid compound being selected
from the group consisting of a linoleic acid compound, a
derivative thereo.f and a combination thereof;
administering a second fatty acid compound to said
woman during the period commencing at the onset of
menopause, said second fatty acid compound being selected
from the group consisting of a linolenic acid compound,
a derivative thereof and a combination thereof;
administering a third fatty acid compound to said
woman during the period commencing at the onset of
CA 02492417 2000-08-28
menopause, said third fatty acid compound being selected
from the group consisting of a docosahexaenoic acid
compound, an omega-3 fatty acid, an omega-2 fatty acid,
a derivative thereof and a combination thereof, and said
third fatty acid compound being provided to the woman
together with said first and second fatty acid compounds;
adm~-.i-stering about 400 mg to about 2500 mg of a
calcium c"mpound or derivative thereof to said woman;
wherein the weight ratio of the sum of the amounts
of said first and second fatty acid compounds to the
amount of said third fatty acid compound is about 1:0.5
to 1.5; and
wherein the weight ratio of the sum of the amounts
of said first, second and third fatty acid compound to
the amount of said calcium compound or derivative thereof
is about 1:0.4 to 50.
Yet another embodiment of the present inventive
subject matter is a method for providing nutritional
supplementation to a menopausal woman while reducing
symptoms associated with menopause, which comprises:
administering a first fatty acid compound to the
woman during a period commencing at the onset of
menopause, said first fatty acid compound being selected
from the gx-oup consisting of a linoleic acid compound, a
derivative thereof and a combination thereof;
administering a second fatty acid compound to said
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woman during the period commencing at the onset of
menopause, said second fatty acid compound being selected
from the group consisting of a linolenic acid compound,
a derivative thereof and a combination thereof;
administering a third fatty acid compound to said
woman during the period commencing at the onset of
menopause, said third fatty acid compound being selected
from the group consisting of a docosahexaenoic acid
compound, an omega-3 fatty acid, an omega-2 fatty acid,
a derivative thereof and a combination thereof, and said
third fatty acid compound being provided to the woman
together with said first and second fatty acid compounds;
administering about 400 mg to 2500 mg of a calcium
compound or derivative thereof to said woman;
administering a therapeutic substance to said woman;
wherein the weight ratio of the sum of the amounts
of said first and second fatty acid compounds to the
amount of said third fatty acid compound is about 1:0.5
to 1.5; and
wherein the weight ratio of the sum of said first,
second and third fatty acid compound to the amount of
said. calcium compound or derivative thereof is about
1:0.4 to 50.
A further embodiment is a method for delaying the
onset of menopause, which comprises: administering an
essential fatty acid to a woman prior to menopause, said
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fatty acici being selected from the group consisting of a
linoleic acid compound, a linolenic acid compound, a
docosahexaenoic acid compound, an omega-3 fatty acid
compound, an omega-2 fatty acid compound, a derivative
thereof and a combination thereof; wherein said essential
fatty acid is administered in an amount sufficient to
delay the onset of menopause.
A still further embodiment is a method for providing
nutritional supplementation to a menopausal woman while
reducing symptoms associated with menopause, which
comprises:
administering a fatty acid compound to the woman
during a period commencing at the onset of menopause,
said fatty acid compound being selected from the group
consisting of a linoleic acid compound, a linolenic acid
compound, a docosahexaenoic acid compound, an omega-3
fatty acid, an omega-2 fatty acid, a derivative thereof
and a combination thereof;
administering about 400 mg to 2500 mg of a calcium
compound or derivative thereof to said woman;
and aciministering a non-nutritional active to said
woman.
Another embodiment is a method for reducing the
possibility of premature menopause, which comprises:
administering an essential fatty acid to a woman prior to
menopause, said fatty acid being selected from the group
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consisting of a linoleic acid compound, a linolenic acid
compound, a docosahexaenoic acid compound, an omega-3
fatty acid compound, an omega-2 fatty acid compound, a
derivative thereof and a combination thereof; wherein
said essential fatty acid is administered in an amount
sufficient to reduce the risk of premature menopause.
An additional embodiment is a method for providing
nutritional supplementation to a premenopausal woman or
a menopausal woman, which comprises: administering to the
premenopausal woman or menopausal woman a biologically
active substance for treating symptoms of menopause;
administering to the premenopausal woman or menopausal
woman a calcium compound or derivative thereof in an
amount of 400 mg to about 2500; and administering to the
premenopausal woman or menopausal woman a folic acid
compound or derivative thereof in an amount of about 0.4
mg to about 5.0 mg.
DETAILED DESCRIPTION OF THE INVENTION
As used herein, "menopausal woman" refers to any
woman who has experienced ovarian failure. The ovarian
failure can be measured by blood tests for low estrogen
levels (estradiol) or elevated gonadotropin levels
(follicle stimulating hormone) . When menopause occurs it
remains for the life of the woman. The term "menopause"
also encompasses the postmenopause or the postmenopausal
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period. The term "menopause" also encompasses natural
menopause and artificial menopause.
"Premenopausal woman" refers to any woman during the
period commencing five years prior to onset of menopause.
"Nutritional stores" refers to the levels of
vitamins, minerals and other nutrients which will be
available for use by the menopausal woman.
"Nutritional status" refers to the presence or
absence of any nutrient deficiency, or in other words,
the extent to which physiological nutrient demands are
being satisfied such that deficiency is avoided.
"Optimize neurological development" refers to
attainment of the highest degree of neurological
development possible through natural processes without
the use of any unnatural substances or procedures, such
as drugs, surgery and the like.
"Biologically active substance" refers to any
substance or substances comprising a drug, active
therapeutic substance, metabolite, medicament, vitamin,
or mineral, any substance used for treatment, prevention,
diagnosis, cure or mitigation of disease or illness, any
substance which affects anatomical structure or
physiological function, or any substance which alters the
impact of external influences on an animal, or metabolite
thereof, and as used herein, encompasses the terms
CA 02492417 2000-08-28
"active substance", "therapeutic substance", "agent",
"active agent", "drug", "medication", "medicine",
"medicant", and other such similar terms.
"Non-nutritional active" refers to any substance or
substances comprising a drug, active therapeutic
substance, metabolite, or medicament, or any other
substance used for treatment, prevention, diagnosis, cure
or mitigation of disease or illness, any substance which
affects anatomical structure or physiological function,
or any substance which alters the impact of external
influences on an -animal, or metabolite thereof, and as
used herein, that is not a vitamin, mineral, or any other
nutritional compound or compositions.
"Specific physiological needs" refers to the unique
requirements for certain levels of certain nutrients by
one class of persons, such as menopausal women,
premenopausal women, postmenopausal women, etc., as
distinguished from other classes.
"Biologically-acceptable" refers to being safe for
human consumption.
"Storage-incompatible substances" refers to
substances that may not be formulated together in a
single dosage unit or stored together in direct contact
because the substances will interact in a negative manner
and also substances that cannot be formulated together in
a single dosage unit because the sum total of the dosage
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amounts of' the substances would result in a single dosage
unit which is too large to be swallowed. The term also
refers to substances which may be stored in direct
contact, however, one of the substances is preferably
formulated in a dosage form which is either not preferred
or incompatible with the other substance. Storage-
incompatibility also refers to two or more substances
wherein at least one substance is a prescription
substance and at least one substance is a non-
prescription substance.
"Storage-incompatibility" refers to the state that
exists between storage-incompatible substances, as
defined above.
The compositions of the present inventive subject
matter provide several specific new and unexpected
benefits. First, the formulations ensure that menopausal
women are provided with adequate energy during the period
of menopause. Secondly, the formulations allow the
menopausal women to maintain adequate fatty acid stores
for both her future use. Thirdly, the fatty acids
optimize the neurological maintenance of the menopausal
women. Fourthly, when administered just prior to
menopause, the present compositions prepare women for the
increased physiological demands and stresses to be placed
upon their bodies. Additionally, the present
compositions provide nutritional supplementation to women
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during the early stage of menopause known as
perimenopause. Finally, the present compositions help
minimize the risk of menopause related disorders and
symptoms resulting from such disorders.
The present inventive subject matter is based, in
part, on the discovery that when compositions having
certain fatty acids, in certain amounts and proportions
to one another, are administered to women just prior to,
during and after menopause, the women will achieve
optimal nutritional supplementation. In particular,
supplementing a menopausal woman's diet with the
formulations described below for a period commencing when
symptoms of menopause are actually experienced, or
preferably just prior to when menopause would generally
be expected, will ensure that the woman has adequate
essential fatty acids for present and future use. The
fatty acid supplement may also further contain vitamins
and=minerals to confer added health benefits to the
menopausal woman. In addition to benefitting humans, the
present invention can also benefit non-human mammals.
The composition of the present invention could be
administered to a mammal in animal feed, pill form, or
other appropriate dosage forms to such mammals.
Without being limited by theory, the present
25' compositions stimulate or play a vital role in one or
more natural biological pathways. For example, the
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arachidonic acid cascade may play a significant role in
the support and maintenance of a menopausal woman's
health. Specifically, in the arachidonic acid cascade,
linoleic acid is converted first to gamma-linolenic acid
and then to further metabolites such as dihomo-gamma-
linolenic acid and arachidonic acid which are precursors
of 1 and 2 series prostaglandin respectively, as shown in
the outline below:
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cis-Linoleic Acid
(9,12-octadecadienoic acid)
GLA
(gamma-linoleic acid i.e.
6,9,12-octadecatrienoic acid)
DGLA DGLA --- I series
ester reserves--> (dihomo-gamma-linoleic acidendoperoxides
(small) i:e. 3,11,14 eicosatrienoic acid) ~
1 serie
AA PG':
(Arachadonic acid, i.e.
5,8,11,14-eicosatrienoic acid)
The present composition may contain an essential
fatty acid compound. The fatty acid compound may be a
linoleic acid compound, derivatives thereof or any
combination of linoleic acid and/or linoleic acid
derivatives. The fatty acid compound may be a linolenic
acid compound, derivatives thereof and/or an combinations
of linolenic acid and/or linoleic acid derivatives. The
fatty acid compound may also be a docosahexaenoic acid
compound, an omega-3 fatty acid compound, an omega-2
fatty acid compound, derivatives thereof or combinations
thereof. The fatty acid may further be a combination of
any of the above discussed fatty acids.
Preferably, the fatty acid compound is present in
the composition in an amount ranging from about 10 mg to
CA 02492417 2000-08-28
1,000 mg. More preferably, the fatty acid compound is
present in the composition in an amount ranging from
about 15 mg to 200 mg, independently of the other fatty
acid compounds. Even more preferably, the fatty acid
compounds is present in the composition in an amount
ranging from about 20 mg to about 100 mg, independently
of the other fatty acid compounds. Most preferably, the
fatty acid compound is present in the composition in an
amount ranging from about 25 mg to 50 mg, independently
of the other fatty acid compounds.
Three fatty acid compounds may be present in the
present composition in critical proportions to one
another. Preferably, the weight ratio of the sum of the
amounts of said first and second fatty acid compounds to
the amount of said third fatty acid compound is about
1:0.5 to 1.5. More preferably, the weight ratio of the
sum of the amounts of said first and second fatty acid
compounds to the amount of said third fatty acid compound
is about 1:0.7 to 1.3. Even more preferably, the weight
ratio of the sum of the amounts of said first and second
fatty acid compounds to the amount of said third fatty
acid compound is about 1:0.9 to 1.2. Most preferably,
the weight ratio of the sum of the amounts of said first
and second fatty acid compounds to the amount of said
third fatty acid compound is about 1:0.9 to 1.1.
The compositions of the present invention may
26
CA 02492417 2000-08-28
incorporate any compound that can react with an essential
fatty acid to form a biochemically active compound.
Preferably,. the compound is a compound which fulfills a
nutritional need, for example, without limitation,
sphingomyelin, myelin, derivatives thereof and
combinations thereof.
Particular classes of fatty acid compound
derivatives used in the present invention, include,
without limitation, phospholipid esters of linoleic acid,
ethers of linoleic acid, sterolderivatives of linoleic
acid, phospholipid esters of linolenic acid, ethers of
linolenic acid, sterolderivatives of linolenic acid and
combinations thereof.
Non-limiting exemplary fatty acid compounds used in
the present invention, include, without limitation,
phosphatidal choline esters of linoleic acid,
phosphatidal ether of linoleic acid, sipolsterol ester of
linoleic acid, phosphatidal choline esters of linolenic
acid, phosphatidal ether of linolenic acid, sipolsterol
ester of linolenic acid and combinations thereof.
The present composition contains a calcium compound,
derivatives thereof or any combination of calcium
compound and derivatives thereof. Preferably, the
calcium is present in the composition in an amount
ranging from about 400 mg to about 2,500 mg. More
preferably, the calcium is present in the composition in
27
CA 02492417 2000-08-28
an amount ranging from about 600 mg to about 1,800 mg.
Even more preferably, the calcium is present in the
composition in an amount ranging from about 800 mg to
about 1600 mg. Most preferably, the calcium is present
in the composition in an amount ranging from about 1,000
mg to about 1400 mg.
The proportion of total fatty acids to total calcium
content in the present inventions is a critical feature.
Where three fatty acid compounds are present,
preferably, the weight ratio of the sum of the amounts of
the first, second and third fatty acid compounds to the
amount of said calcium compound or derivative thereof is
about 1:0.4 to 50. More preferably, the weight ratio of
the sum of the amounts of the first, second and third
fatty acid compounds to the amount of said calcium
compound or derivative thereof is about 1:4 to 20. Even
more preferably, the weight ratio of the sum of the
amounts of the first, second and third fatty acid
compounds to the amount of said calcium compound or
derivative thereof is about 1:7 to 15. Most preferably,
the weight ratio of the sum of the amounts of the first,
second and third fatty acid compounds to the amount of
said calcium compound or derivative thereof is about 1:10
to 14.
The fatty acids of the present inventive subject
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CA 02492417 2000-08-28
matter may be used as such or as biologically acceptable
and physiologically equivalent derivatives as, for
example, detailed later herein. Reference to any of the
fatty acids including reference in the claims is to be
taken as including reference to the acids when in the
form of such derivatives. Equivalence is demonstrated by
entry into the biosynthetic pathways of the body as
evidenced by effects corresponding to those of the acids
themselves or their natural glyceride esters. Thus,
indirect identification of useful derivatives is by their
having the valuable effect in the body of the fatty acid
itself, but conversion, for example, of gamma-linolenic
acid to dihomo-gamma-linolenic acid and on to arachidonic
acid can be shown directly by gas chromatographic
analysis of concentrations in blood, body fat, or other
tissue by standard techniques, well known to persons of
ordinary skill in the art to which the present inventive
subject matter pertains.
Derivatives of linoleic acid, as used in the present
inventive subject matter, include, without limitation,
salts of linoleic acid, alkaline salts of linoleic acid,
esters of linoleic acid and combinations thereof.
Derivatives of linolenic acid, as used in the present
inventive subject matter, include, without limitation,
salts of linolenic acid, alkaline salts of linolenic
acid, esters of linolenic acid and combinations thereof.
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CA 02492417 2000-08-28
The salts and alkaline salts herein refer to those
regularly used organic or inorganic salts which are
acceptable for pharmaceutical use. Non-limiting
exemplary linolenic acids include gamma-linoleic acid and
dihomo-gamma-linolenic acid.
The fatty acids of the present inventive subject
matter may. be from any source, including, without
limitation, natural or synthetic oils, fats, waxes or
combinations thereof. Moreover, the fatty acids herein
may be derived, without limitation, from non-hydrogenated
oils, partially hydrogenated oils, fully hydrogenated
oils or combinations thereof. Non-limiting exemplary
sources of fatty acids include seed oil, fish or marine
oil, canola oil, vegetable oil, safflower oil, sunflower
oil, nasturtium seed oil, mustard seed oil, olive oil,
sesame oil, soybean oil, corn oil, peanut oil, cottonseed
oil, rice bran oil, babassu nut oil, palm oil, low erucic
rapeseed oil, palm kernel oil, lupin oil, coconut oil,
flaxseed oil, evening primrose oil, jojoba, tallow, beef
tallow, butter, chicken fat, lard, dairy butterfat, shea
butter or combinations thereof. Specific non-limiting
exemplary fish or marine oil sources include shellfish
oil, tuna oil, mackerel oil, salmon oil, menhaden,
anchovy, herring, trout, sardines or combinations
thereof. Preferably, the source of the fatty acids is
fish or marine oil, soybean oil or flaxseed oil.
CA 02492417 2000-08-28
Calcium compounds include, but are not limited to,
any of the well known calcium supplements, such as
calcium carbonate, calcium sulfate, calcium oxide,
calcium hydroxide, calcium apatite, calcium citrate-
malate, bone meal, oyster shell, calcium gluconate,
calcium lactate, calcium phosphate, calcium levulinate,
and the like. Derivatives of calcium compounds, as used
herein, include, without limitation, salts of calcium,
alkaline salts of calcium, esters of calcium, and
combinations thereof. The salts and alkaline salts
herein refer to those regularly used organic or inorganic
salts which are acceptable for pharmaceutical use. The
calcium of the present composition may be from any
source, without limitation.
Folic acid is also incorporated into the composition
of the present inventive subject matter. Preferably,
folic acid is present in an amount ranging from about 0.4
mg to about 5.0 mg. More preferably, folic acid is
present in an amount ranging from about 0.6 mg to about
1.3 mg. Even more preferably, folic acid is present in
an amount ranging from about 0.8 mg to about 1.2 mg.
Most preferably, folic acid is present in an amount
ranging from about 0.9 mg to about 1.1 mg.
The present composition may optionally contain
additional vitamins and biologically-acceptable minerals.
Non-limiting exemplary vitamins and biologically
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CA 02492417 2000-08-28
acceptable minerals and their derivatives thereof for
inclusion in the present compositions include vitamin A,
B vitamins, vitamin C, vitamin D, vitamin E, vitamin K,
iron, calcium, magnesium, potassium, copper, chromium,
zinc, molybdenum, iodine, boron, selenium, manganese,
bioflavonoid, derivatives thereof or combinations
thereof. These vitamins and minerals may be from any
source or combination of sources, without limitation.
Non-limiting exemplary B vitamins include, without
limitation, thiamine, niacinamide, pyridoxine,
riboflavin, cyanocobalamin, biotin, pantothenic acid or
combinations thereof. Other nutritionally active
compounds may also be present, including without
limitation, fiber, carbohydrates, fats, proteins, amino
1.5 acids, derivatives thereof and combinations thereof.
When vitamin C is present in the composition of the
present inventive subject matter, it is preferably
present in an amount ranging from about 10 mg to about
600 mg. More preferably, the vitamin C is present in an
amount ranging from about 25 mg to about 500 mg. Even
more preferably, the vitamin C is present in an immediate
release form in an amount ranging from about 25 mg to
about 50 mg. Most preferably, the vitamin C is present
in a controlled release form in an amount ranging from
about 250 mg to about 500 mg.
When vitamin E is present in the composition of the
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CA 02492417 2000-08-28
present inventive subject matter, it is preferably
present in an amount ranging from about 5 mg to about 500
mg. More preferably, the vitamin E is present in an
amount ranging from about 10 mg to about 400 mg. Even
more preferably, the vitamin E is present in a controlled
release form in an amount ranging from about 250 mg to
about 400 mg. Most preferably, the vitamin E is present
in an immediate release form in an amount ranging from
about 10 mg to about 50 mg.
Vitamin B6 may also be present in the composition of
the present inventive subject matter. Vitamin B6 is
preferably present in an amount ranging from about 5 mg
to about 200 mg. More preferably, vitamin B6 is present
in an amount ranging from about 10 mg to about 50 mg.
Even more preferably, vitamin B6 is present in an amount
ranging from 15 mg to about 40 mg. Most preferably,
vitamin B6 is present in a controlled release form in an
amount ranging from 20 mg to about 30 mg.
Vitamin B12 may also be incorporated into the
present composition. Preferably,, the vitamin B12 is
present in an amount ranging from about 25 mcg to about
75 mcg. More preferably, the vitamin B12 is present in
an amount ranging from about 35 mcg to about 65 mcg.
Even more preferably, the vitamin B12 is present in an
amount ranging from about 40 mcg to about 60 mcg. Most
preferably, the vitamin B12 is present in an amount
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CA 02492417 2000-08-28
ranging from about 45 mcg to about 55 mcg.
Vitamin D may also be incorporated into the present
composition. Preferably, vitamin D is present in an
amount ranging from about 200 IU to about 625 IU. More
preferably, vitamin D is present in an amount ranging
from about 300 IU to about 500 IU. Even more preferably,
vitamin D is present in an amount ranging from about 350
IU to about 450 IU. Most preferably, vitamin D is
present in an amount ranging from about 375 IU to about
425 IU.
Vitamin. A may also be incorporated into the present
composition. Preferably, vitamin A is present in the
composition in an amount ranging from about 2,500 IU to
about 6,500 IU. More preferably, vitamin A is present in
the composition in an amount ranging from about 4,000 IU
to about 6,000 IU. Even more preferably, vitamin A is
present in the composition in an amount ranging from
about 4,500 IU to about
5,500 IU. Most preferably, vitamin A is present in the
composition in an amount ranging from about 4,750 IU to
about 5,250 IU.
Magnesium, when present, is preferably in the
composition of the present inventive subject matter in an
amount ranging from about 25 mg to about 400 mg. More
preferably, magnesium is present in the composition of
the present inventive subject matter in an immediate
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CA 02492417 2000-08-28
release form in an amount ranging from about 25 mg to
about 100 mg. Even more preferably, magnesium is present
in the composition of the present inventive subject
matter in a controlled release form in an amount ranging
from about 100 mg to about 400 mg. Acceptable magnesium
compounds which may be incorporated into the present
inventive subject matter include, but are not limited to,
magnesium stearate, magnesium carbonate, magnesium oxide,
magnesium hydroxide and magnesium sulfate.
The composition of the present inventive subject
matter may also include one or more biologically active
substances or therapeutic substances, including, without
limitation, hormones, steroids, fiber, estrogens,
progestins, sedative-hypnotics, barbiturates,
benzodiazepines, antidepressants, tranquilizers,
sedatives, osteoporotics, anti-platelets,
aminobisphosphonates, herbals, herbal derivatives, plant
derivatives, phyto-chemical derivatives and combinations
thereof.
If the non-nutritional active is a hormone, the
hormone is administered in a dosage amount ranging from
about 0.15 mg to about 11.25 mg. If the non-nutritional
active is an osteoporotic, the osteoporotic is
administered in a dosage amount ranging from about 2.5 mg
to about 60 mg.
Non-limiting exemplary therapeutic substances include,
CA 02492417 2000-08-28
medroxyprogesterone acetate, megestrol acetate,
clonidine, norethindrone acetate, ethinyl estradiol,
conjugated estrogen, natural estrogen, synthetic
estrogen, estradiol, progesterone, clomiphene, clomiphene
citrate, zuclomiphene, zuclomiphene citrate,
enclomiphene, enclomiphene citrate, aspirin, calcitonin,
alendronate, etidronate, pamidronate, clodronate,
tiludronate, residronate, ibandronate and combinations
thereof.
Non-limiting exemplary herbals and herbal
derivatives include agrimony, alfalfa, aloe vera,
amaranth, angelica, anise, barberry, basil, bayberry, bee
pollen, birch, bistort, blackberry, black cohosh, black
walnut, blessed thistle, blue cohosh, blue vervain,
boneset, borage, buchu, buckthorn, bugleweed, burdock,
capsicum, cayenne, caraway, cascara sagrada, catnip,
celery, centaury, chamomile, chaparral, chickweed,
chicory, chinchona, cloves, coltsfoot, comfrey, cornsilk,
couch grass, cramp bark, culver's root, cyani,
cornflower, damiana, dandelion, devils claw, dong quai,
echinacea, elecampane, ephedra, eucalyptus, evening
primrose, eyebright, false unicorn, fennel, fenugreek,
figwort, flaxseed, garlic, gentian, ginger, ginseng,
golden seal, gotu kola, gum weed, hawthorn, hops,
horehound, horseradish, horsetail, hoshouwu, hydrangea,
hyssop, iceland moss, irish moss, jojoba, juniper, kelp,
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CA 02492417 2000-08-28
lady's slipper, lemon grass, licorice, lobelia, mandrake,
marigold, marjoram, marshmallow, mistletoe, mullein,
mustard, myrrh, nettle, oatstraw, oregon grape, papaya,
parsley, passion flower, peach, pennyroyal, peppermint,
periwinkle, plantain, pleurisy root, pokeweed, prickly
ash, psyllium, quassia, queen of the meadow, red clover,
red raspberry, redmond clay, rhubarb, rose hips,
rosemary, rue, safflower, saffron, sage, St. Johnswort,
sarsaparilla, sassafras, saw palmetto, scullcap, senega,
senna, shepherd's purse, slippery elm, spearmint,
spikenard, squawvine, stillingia, strawberry, taheebo,
thyme, uva ursi, valerian, violet, watercress, white oak
bark, white pine bark, wild cherry, wild lettuce, wild
yam, willow, wintergreen, witch hazel, wood betony,
wormwood, yarrow, yellow dock, yerba santa, yucca and
combinations thereof. Herbal derivatives, as used
herein, refers to herbal extracts, and substances derived
from plants and plant parts, such as leaves, flowers and
roots, without limitation. Preferably, the herbal or
herbal derivative is black cohosh, licorice, false
unicorn, siberian ginseng, sarsaparilla, squaw vine,
blessed thistle and combinations thereof.
Various additives may be incorporated into the
present composition. Optional additives of the present
composition include, without limitation, starches,
sugars, fats, antioxidants, amino acids, proteins,
37
CA 02492417 2000-08-28
nucleic acids, electrolytes, derivatives thereof or
combinations thereof.
Non-limiting exemplary amino acids of the present
inventive subject matter include histidine, isoleucine,
leucine, lysine, methionine, phenylalanine, threonine,
tryptophan, valine, alanine, arginine, asparagine,
aspartic acid, cysteine, glutamic acid, glutamine,
glycine, proline, serine, tyrosine, derivatives thereof,
and combinations thereof. Preferably, the amino acid
present is leucine, isoleucine, valine, derivatives
thereof or combinations thereof.
The compositions, methods and drug delivery regimens
of the present inventive subject matter may facilitate
the simultaneous administration of storage-incompatible
substances, particularly storage incompatible substances
tailored to the needs of premenopausal and menopausal
women. Storage-incompatible substances may be any
substances that may not be formulated together in a
single dosage unit or stored together in direct contact
because the substances will interact in a negative manner
and also substances that cannot be formulated together in
a single dosage unit because the sum total of the dosage
amounts of the substances would result in a single dosage
unit which is too large to be swallowed. Storage-
incompatible substances also include those substances
which may be stored in direct contact, however, one of
38
CA 02492417 2000-08-28
the substances is preferably formulated in a dosage form
which is either not preferred or incompatible with the
other substance. The storage-incompatible substances may
include any storage-incompatible substances, without
limitation.
For example, the storage incompatible substances may
be hydrophobic compounds and hydrophilic compounds,
olefinic compounds and non-olefinic compounds, pH
sensitive compounds and non-pH sensitive compounds,
substances requiring an anhydrous environment and
substances requiring a non-anhydrous environment, acidic
drugs and basic drugs, effervescent tablets and high
water content drugs or dosage forms, gelatin capsules and
aldehydes, quaternar.y ammonium compounds and anionic
substances or any combination of the above.
Storage incompatible substances also include
substances that cannot be formulated together in a single
dosage unit because the sum total of the dosage amounts
of the substances results in a single dosage unit too
large to swallow. The compositions, methods and drug
delivery regimens of the present inventive subject matter
address this problem by separating the large dosage into
multiple doses small enough to swallow comfortably, while
keeping all of the substances and doses together in one
package.
Non-limiting exemplary storage incompatible
39
CA 02492417 2005-07-20
substances include, without limitation, ascorbic acid and
aluminum hydroxide, ascorbic acid and sodium bicarbonate,
citric acid and sodium carbonate, folic acid and calcium
carbonate, activated charcoal and amyl nitrate, gelatin
capsules and formaldehyde, gelatine capsules and
gluteraldehyde, konicin chloride and soap, cetylpyridinium
chloride and sodium stearate, omega fatty acids and
combinations thereof.
It is also possible in the nutritional composition
of the present inventive subject matter for the dosage
form to combine any forms of release well known to
persons of ordinary skill in the art. These include,
without limitation, immediate release, extended release,
pulse release, variable release, controlled release,
timed release, sustained release, delayed release, long
acting, and combinations thereof.. The ability to obtain
immediate release, extended release, pulse release,
variable release, controlled release, timed release,
sustained release, delayed release, long acting
characteristics and combinations thereof is performed
using well known procedures and techniques available to
the ordinary artisan. Each of these specific techniques
or procedures for obtaining the release characteristics
does not constitute an inventive aspect of this inventive
subject matter all of which procedures are well known to
those of ordinary skill in the art. As used herein, a
CA 02492417 2000-08-28
"controlled release form" means any form having at least
one component formulated for controlled release. As used
herein, "immediate release form" means any form having
all its components formulated for immediate release.
Any biologically-acceptable dosage form well known
to persons of ordinary skill in the art, and combinations
thereof, are contemplated by the inventive subject
matter. Examples of such dosage forms include, without
limitation, chewable tablets, quick dissolve tablets,
effervescent tablets, reconstitutable powders, elixirs,
liquids, solutions, suspensions, emulsions, tablets,
multi-layer tablets, bi-layer tablets, capsules, soft
gelatin capsules, hard gelatin capsules, caplets,
lozenges, chewable lozenges, beads, powders, granules,
particles, microparticles, dispersible granules, cachets,
douches, suppositories, creams, topicals, inhalants,
aerosol inhalants, patches, particle inhalants, implants,
depot implants, ingestibles, injectables, infusions,
health bars, confections, animal feeds, cereals, yogurts,
cereal coatings, foods, nutritive foods, functional foods
and combinations thereof. The preparation of the above
dosage forms are well known to persons of ordinary skill
in the art.
The following procedures represent, without
limitation, acceptable methods of preparing formulations
falling within the scope of the inventive subject matter.
41
CA 02492417 2000-08-28
For example, animal feed may be made by methods well
known to persons of ordinary skill in the art. Animal
feeds may be prepared by mixing the formulation with
binding ingredients to form a plastic mass. The mass is
then extruded under high pressure to form tubular (or
"spaghetti-like") structures that are cut to pellet'size
and dried.
Quick dissolve tablets may be prepared, for example,
without limitation, by mixing the formulation with agents
such as sugars and cellulose derivatives, which promote
dissolution or disintegration of the resultant tablet
after oral administration, usually within 30 seconds.
Cereal coatings may be prepared, for example,
without limitation, by passing the cereal formulation,
after it has been formed into pellets, flakes, or other
geometric shapes, under a precision spray coating device
to deposit a film of active ingredients, plus excipients
onto the surface of the formed elements. The units thus
treated are then dried to form a cereal coating.
For example, health bars may be prepared, without
limitation, by mixing the formulation plus excipients
(e.g., binders, fillers, flavors, colors, etc.) to a
plastic mass consistency. The mass is then either
extended or molded to form "candy bar" shapes that are
2.5 then dried or allowed to solidify to form the final
product.
42
CA 02492417 2000-08-28
Soft gel or soft gelatin capsules may be prepared,
for example, without limitation, by dispersing the
formulation in an appropriate vehicle (vegetable oils are
commonly used) to form a high viscosity mixture. This
mixture is then encapsulated with a gelatin based film
using technology and machinery known to those in the soft
gel industry. The industrial units so formed are then
dried to constant weight.
Chewable tablets, for example, without limitation,
may be prepared by mixing the formulations with
excipients designed to form a relatively soft, flavored,
tablet dosage form that is intended to be chewed rather
than swallowed. Conventional tablet machinery and
procedures, that is both direct compression and
granulation, i.e., or slugging, before compression, can
be utilized. Those individuals involved in
pharmaceutical solid dosage form production are well
versed in the processes and the machinery used as the
chewable dosage form is a very common dosage form in the
pharmaceutical industry.
Film coated tablets, for example, without
limitation, may be prepared by coating tablets using
techniques such as rotating pan coating methods or air
suspension methods to deposit a contiguous film layer on
a tablet. This procedure is often done to improve the
aesthetic appearance of tablets, but may also be done to
43
CA 02492417 2000-08-28
improve the swallowing of tablets, or to mask an
obnoxious odor or taste, or to improve the usual
properties of an unsightly uncoated tablet.
Compressed tablets, for example, without limitation,
may be prepared by mixing the formulation with excipients
intended to add binding qualities to disintegration
qualities. The mixture is either directly compressed or
granulated then compressed using methods and machinery
quite well. known to those in the industry. The resultant
compressed tablet dosage units are then packaged
according to market need, i.e., unit dose, rolls, bulk
bottles, blister packs, etc.
The present inventive subject matter contemplates
nutritional compositions formulated for administration by
any route, including without limitation, oral, buccal,
sublingual, rectal, parenteral, topical, inhalational,
injectable and transdermal. The physicochemical
properties . of nutritional compositions, their
formulations, and the routes of administration are
important in absorption. Absorption refers to the
process of nutritional composition movement from the site
of administration toward the systemic circulation. Most
orally administered nutritional compositions are in the
form of tablets or capsules primarily for convenience,
economy, stability, and patient acceptance. They must
disintegrate and dissolve before absorption can occur:
44
CA 02492417 2000-08-28
Using the present inventive subject matter with any of
the above routes of administration or dosage forms is
performed using well known procedures and techniques
available to the ordinary skilled artisan.
The present inventive subject matter contemplates
the use of biologically-acceptable carriers which may be
prepared from a wide range of materials. Without being
limited thereto, such materials include diluents, binders
and adhesives, lubricants, plasticizers, disintegrants,
colorants, bulking substances, flavorings, sweeteners and
miscellaneous materials such as buffers and adsorbents in
order to prepare a particular medicated composition.
Binders may be selected from a wide range of
materials such as hydroxypropylmethylcellulose,
ethylcellulose, or other suitable cellulose derivatives,
povidone, acrylic and methacrylic acid co-polymers,
pharmaceutical glaze, gums, milk derivatives, such as
whey, starches, and derivatives, as well as other
conventional binders well known to persons skilled in the
art. Exemplary non-limiting solvents are water, ethanol,
isopropyl alcohol, methylene chloride or mixtures and
combinations thereof. Exemplary non-limiting bulking
.substances include sugar, lactose, gelatin, starch, and
silicon dioxide.
The plasticizers used in the dissolution modifying
system are preferably previously dissolved in an organic
CA 02492417 2000-08-28
solvent and added in solution form. Preferred
plasticizers may be selected from the group consisting of
diethyl phthalate, diethyl sebacate, triethyl citrate,
cronotic acid, propylene glycol, butyl phthalate, dibutyl
sebacate, caster oil and mixtures thereof, without
limitation. As is evident, the plasticizers may be
hydrophobic as well as hydrophilic in nature. Water-
insoluble hydrophobic substances, such as diethyl
phthalate, diethyl sebacate and caster oil are used to
delay the release of water-soluble vitamins, such as
vitamin B6 and vitamin C. In contrast, hydrophilic
plasticizers are used when water-insoluble vitamins are
employed which aid in dissolving the encapsulated film,
making channels in the surface, which aid in nutritional
compositiori release.
The composition of the present inventive subject
matter may be administered in a partial, i.e., fractional
dose, one or more times during a 24 hour period, a single
dose during a 24 hour period of time, a double dose
during a 24 hour period of time, or more than a double
dose during a 24 hour period of time. Fractional, double
or other multiple doses may be taken simultaneously or at
different times during the 24 hour period. The doses may
be uneven doses with regard to one another or with regard
to the individual components at different administration
times. For example, without limitation, the amount of
46
CA 02492417 2000-08-28
calcium in a morning dose is different from the amount of
calcium in an evening dose.
The compositions of the present invention are
intended for use by humans and other mammals. The
dosages are adjusted according to body weight and thus
may be set forth herein on a per body weight basis. For
example, if the formula specifies a range of about 10-
1000 mg for a 55 kg individual, that range would be
adjusted for a 35 kg individual to about 6.3-63 mg (e.g.,
the lower range limit= (35 kg/55 kg) *10mg =6.3 mg).
Decimal amounts may be rounded to the nearest whole
number. In the above manner the present compositions may
thus be adapted to be suitable for any individual,
including any mammal, regardless of its size.
The present composition is adapted to meet the
specific physiological needs of a menopausal woman.
For example, the formulations may focus on special
nutritional needs of a menopausal woman that are not
generally or adequately addressed in nutritional or
dietary supplements, such as essential fatty acids,
without limitation. The iron and calcium, when present,
are provided in amounts to optimize nutritional benefit
to the menopausal woman, while minimizing unpleasant side
effects which may accompany overly large doses. The
formulation can be further tailored based upon the
specific needs, genetic predispositions or identified
47
CA 02492417 2000-08-28
deficiencies of individual women, on either a generalized
or case by case basis for greater specificity. Further,
the composition may be specifically adapted for treating
conditions associated with menopause or to maximize
neurological maintenance of a menopausal woman. The
composition may also be.adapted for inhibiting loss in
bone mass and preventing deficiency of essential fatty
acids in menopausal women. Moreover, the present
composition can be used as one component of a prescribed
therapy.
The compositions of the inventive subject matter may
be provided in a blister pack or other such
pharmaceutical package, without limitation. Further, the
compositions of the present inventive subject matter may
further include or be accompanied by indicia allowing
women to identify the compositions as products for
menopausal women. The indicia may further additionally
include an indication of the above specified time periods
for using said compositions. For example, without
limitation, the indicia may be time indicia indicating a
specific or general time of day for administration of the
composition, or the indicia may be a day indicia
indicating a day of the week for administration of the
composition.
The composition of the present invention may be used
prior to and during menopause. Use of the compositions
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CA 02492417 2000-08-28
may commence at the onset of menopause. The composition
of the present inventive subject matter is preferably
administered during a period commencing no later than the
appearance of the first symptoms associated with
menopause and continuing throughout a woman's life. More
preferably, the composition is administered during a
period of time commencing just prior to menopause or just
prior to any symptoms of menopause. The phrases "just
prior to menopause" and "prior to any symptoms of
menopause" are intended herein to include commencement of
administration of compositions approximately one month to
five years prior to an age generally identified with
initiation of menopause.
Preferably, the commencement of administration of
the composition is when the woman is thirty five to fifty
years of age. More preferably, the commencement of
administration is one month prior to the woman turning
forty years of age. Even more preferably, the
commencement of administration is one year prior to the
20. woman turning forty years of age. Most preferably, the
commencement of administration is five years prior to the
woman turning forty years of age.
The present inventive subject matter includes a
method for providing nutritional supplementation to a
menopausal woman. The methods include administration of
the present composition to women during a critical
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CA 02492417 2000-08-28
period. The critical period of administration is the
period commencing just prior to menopause and continuing
through the postmenopausal period of a woman's life.
The method of the present inventive subject matter
may prevent or at least minimize fatty acid deficiency in
menopausal women. The present method may also be used to
prevent or treat symptoms associated with menopause.
Further, the present method may inhibit the loss in bone
mass commonly experienced by menopausal women. The
present method may delay onset of menopause andlor reduce
possibility of premature menopause.
The present methods may be carried out alone-or in
conjunctiori with a therapeutic therapy or regimen,
without limitation. The therapeutic therapy or regimen
may be for 'treating symptoms associated with menopause or
may be entirely unrelated to menopause. For example,
without limitation, the present method may be
incorporated as part of hormonal or estrogen therapy, or
in combination with dietary manipulation.
The foregoing is considered as illustrative only of
the principles of the inventive subject matter. Further,
since numerous modifications and changes will readily
occur to those skilled in the art, it is not desired to
limit the inventive subject matter to the exact
construction and operation shown and described, and
accordingly all suitable modifications and equivalents
CA 02492417 2000-08-28
may be resorted to, falling within the scope of the
inventive subject matter.
The following examples are illustrative of preferred
embodiments of the inventive subject matter and are not
to be construed as limiting the inventive subject matter
thereto. All percentages are based on the percent by
weight of the final delivery system or formulation
prepared unless otherwise indicated and all totals equal
100% by weight.
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CA 02492417 2000-08-28
EXAMPLES
Example 1
The following formulations are used to prepare
compositions for administration to premenopausal and
menopausal women:
Component Dose Units
Vitamin A (Beta Carotene) 5,000 I.U.
Vitamin D 400 I.U.
Vitamin E 400 I.U.
Vitamin C 100 mg.
Vitamin B1 20 mg.
Vitamin B2 20 mg.
Vitamin B6 25 mg.
Vitamin B12 50 mcg.
Vitamin B3 100 mg.
Folic Acid 1.0 mg.
Calcium Carbonate 1,200 mg.
Copper 2 mg.
Zinc 15 mg.
Selenium 65 mcg.
DHA/Liriolenic/Linoleic Acid 50/25/25 mg.
It would be anticipated that upon administration of
the above composition, an average normal menopausal woman
would be expected to have reduced incidence of
nutritional deficiency and reduced menopausal.-related
symptoms or disorders when compared to an average normal
menopausal woman following a conventional nutritional
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CA 02492417 2000-08-28
regimen.
Example 2
The following compositions are for administration to
premenopausal women and menopausal women in accordance
with the regimen indicated below:
Regimen Component Dose
First Morning Calcium Carbonate 350 mg
Tablet (orange):
B Complex 55 mg
Second Morning Calcium Carbonate 350 mg
Tablet (white):
Vitamin A 3,000 IU
Vitamin C 100 IU
Vitamin D 400 IU
Selenium 65 mcg
Zinc 15 mg
Copper 2 mg
Evening Tablet Calcium Carbonate 350 mg
B Complex 110 mg
Vitamin A 2,000 IU
Folic Acid 1 mg
Evening Capsule Vitamin E 400 IU
DHA 50 mg
Linolenic Acid 25 mg
Linoleic Acid 25 mg
Calcium Carbonate 150 mg
It would be anticipated that upon following the
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CA 02492417 2000-08-28
above regimen, an average normal menopausal woman would
be expected to have reduced incidence of nutritional
deficiency and reduced menopausal-related symptoms or
disorders when compared to an average normal menopausal
woman following a conventional nutritional regimen.
Example 3
A soft gelatin supplement in accordance with the
compositions of Examples 1 and 2 above, may be prepared,
by first combining mineral oil and soybean oil in a first
vessel and blending it to form a uniform oil mixture,
heating the oil mixture to 45 degrees Celsius, and then
adding propylene glycol. In a second vessel preheated to
70 degrees Celsius, yellow beeswax and soybean oil are
added and blended until a uniform wax mixture is formed.
The wax mixture is cooled to 35 degrees Celsius and then
added to tt-e oil mixture. To this combined oil and wax
mixture, folic acid, vitamin B61 iron, magnesium, and
calcium are then added and blended together to form a
uniform biologically active mixture. The mixture is then
cooled to 30 degrees Celsius to form a viscous
biologically active core composition, after which time
the composition is ready for encapsulation in a soft
gelatin shell.
A soft gelatin shell is prepared by heating purified
water in a suitable vessel and then adding gelatin. This
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CA 02492417 2000-08-28
water gelatin mixture is mixed until the gelatin is fully
dissolved, and then glycerin, preservatives, one or more
flavors, and one or more colorants are added. This
gelatin inixture is blended well and cooled. The shells
are then filled with the core composition and formed in
accordance with soft gelatin techniques commonly used and
well known to persons of skill in the art.
Example 4
The following compositions are for administration to
premenopausal women and menopausal women in accordance
with the regimen indicated below:
CA 02492417 2000-08-28
Regimen Component Dose
First Morning Calcium Carbonate 350 mg
Tablet (orange) :
B Complex 55 mg
Second Morning Calcium Carbonate 350 mg
Tablet (white) :
Vitamin A 3,000 IU
Vitamin C 100 IU
Vitamin D 400 IU
Selenium 65 mcg
Zinc 15 mg
Copper 2 mg
Evening Tablet Calcium Carbonate 350 mg
B Complex 110 mg
Vitamin A 2,000 IU
Folic Acid 1 mg
Evening Capsule Vitamin E 400 IU
DHA 50 mg
Linolenic Acid 25 mg
Linoleic Acid 25 mg
Calcium Carbonate 150 mg
Evening Tablet Alendronate 10 mg
It would be anticipated that upon following the
above regimen, an average normal menopausal woman would
be expected to have reduced incidence of nutritional
deficiency and reduced menopausal-related symptoms or
disorders when compared to an average normal menopausal
woman following a conventional nutritional regimen.
:15
56
CA 02492417 2000-08-28
Example 5
The following compositions are for administration to
premenopausal women and menopausal women in accordance
with the regimen indicated below:
Regimen Component Dose
First Morni.ng Calcium Carbonate 350 mg
Tablet (orange) :
B Complex 55 mg
Second Morning Calcium Carbonate 350 mg
Tablet (white) :
Vitamin A 3,000 IU
Vitamin C 100 IU
Vitamin D 400 IU
Selenium 65 mcg
Zinc 15 mg
Copper 2 mg
Evening Tablet Calcium Carbonate 350 mg
B Complex 110 mg
Vitamin A 2,000 IU
Folic Acid 1 mg
Evening Capsule Vitamin E 400 IU
DHA 50 mg
Linolenic Acid 25 mg
Linoleic Acid 25 mg
Calcium Carbonate 150 mg
Evening Tablet PREMPRO'N
conjugated estrogens 2.5 mg
progesterone 2.5 mg
It would be anticipated that upon following the
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CA 02492417 2000-08-28
above regimen, an average normal menopausal woman would
be expected to have reduced incidence of nutritional
deficiency and reduced menopausal-related symptoms or
disorders when compared to an average normal menopausal
woman following a conventional nutritional regimen.
The inventive subject matter being thus described,
it will be apparent that the same may be varied in many
ways. Such variations are not to be regarded as a
departure from the spirit and scope of the inventive
subject matter, and all such modifications are intended
to be within the scope of the appended claims.
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