Note: Descriptions are shown in the official language in which they were submitted.
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NUTRIENT AND THERAPEUTIC COMPOSITIONS
FOR THE TREATMENT OF CANCER
FIELD OF THE INVENTION
This invention relates to nutrient compositions and to therapeutic
compositions for the
amelioration of cancer. Cancer-protective and cancer-therapeutic compositions
of this
invention include antioxidants, neovascular regulators, promoters or cofactors
involved in
collagen synthesis, as well as vitamins and minerals to supplement nutrient
deficiencies.
BACKGROUND OF THE INVENTION
Cancerous cells exhibit certain characteristics that distinguish them from
normal cells.
These cells exhibit aberrant metabolism and growth, often the result of
genetic damage; they
exhibit proliferation due to inappropriate vascularization leading to tumor
development; and
they can undergo metastasis leading to the spread and recurrence of cancer.
Current cancer therapies are most often directed to the removal of cancerous
tissue
and the direct destruction of cancerous cells. The present invention is, in
contrast, designed
to utilize mufti-component formulations the combined ingredients of which
simultaneously
interfere with a variety of factors or mechanisms that promote the generation,
growth and
spread of cancerous cells and tissue. More specifically the formulas of the
present invention
contain components which inhibit the development of cancer cells, inhibit
proliferation of
cancer cells and inhibit metathesis. Formulas of this invention contain
additional components
that promote cellular repair and the restoration of collagen matrices in
tissues. Further
formula ingredients are provided to restore and maintain pH balance and to
stimulate the
immune system. Vitamins and minerals are also included to supplement
deficiencies
including those that can result from cachexia induced by tumor development and
growth and
help restore normal biochemical function to cells and tissue. Additional
formula components
are included to control the level and type of blood-born lipids which may be
related to
increased cancer risk. The control of lipoprotein (a) is of particular
importance. Further,
optional formula ingredients can be included to control blood glucose levels,
control insulin
levels and reduce homocysteine levels.
The mufti-component compositions of this invention and treatment methods using
them are based, at least in part, on a recognition that cancer is the result
of a mufti-factor
etiology requiring utilization of multiple biochemical factors to successfully
ameliorate or
reverse conditions or symptoms of cancer. Further, the protective and
therapeutic formulas of
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this invention include components that are directed to simultaneously inhibit
cancer at
various stages, i.e., to inhibit development of cancer cells, to inhibit
growth and proliferation
of cancer cells and tissue and to inhibit metathesis.
Formulas provided in the present invention are useful as cancer-protective
nutrient
compositions that may be employed as dietary supplements and as cancer
therapeutic
compositions that may be combined with traditional forms of cancer treatment.
Additional
formulas include those directed to female cancers, including hormone-dependent
cancers.
Compositions of this invention can employ a mixture of different components
having
the same or similar biochemical or therapeutic functionality. These
functionally similar
components may differ in source (e.g., extracts of different plants), differ
in chemical
structure, differ in specific site of action and/or differ in effective half
life on administration.
Such combinations of different components with similar activities provide
synergistic
nonadditive benefits and improvements. Components of the compositions of this
invention
may themselves be mufti-component mixtures with each subcomponent having one
or more
differing functionalities. Different composition components may have more than
one
biological function in the mixture and different components may have distinct,
yet
overlapping, biological functions. The use of functionally similar components
which are
structurally distinct or derived from different sources allows the inclusion
of sufficiently high
levels of total material to achieve a desired level of activity while avoiding
the potential toxic
effect that may result from use of high levels of any single component.
Different but
functionally similar components can have somewhat different site-specific
features.
Additionally, distinct but functionally similar components can have different
half lives
potentially providing for extended effectiveness of the formula.
SUMMARY OF THE INVENTION
The cancer protective and therapeutic compositions of this invention combine
components which control oxidative stress, provide for appropriate neovascular
regulation,
provide factors necessary for stimulation or promotion of collagen maintenance
and synthesis
and tissue restoration. Preferred combinations of antioxidants and neovascular
regulators
include combinations of a plant extract providing antioxidant effect
comprising
bioflavanoids, e.g., proanthocyanidins, with a neovascular regulator selected
from the group
genistein, daidzein, soy isolate (a specific source of plant isoflavones,
e.g., genistein, and
daidzein), cartilage or preferably chondroitin sulphate. A preferred
neovascular regulator is
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genistein from soy isolate. Preferred compositions can further comprise
components which
regulate blood lipids, glucose or insulin, decrease homocysteine levels and
stimulate or
promote immune response or cell differentiation. Preferred compositions-can
further
comprise components which provide cell protection from mutation and toxins.
Without wishing to be bound by any particular theory, the antioxidant
components of
the present formulas are believed to protect cells from damage which may lead
to mutation
and the generation of cancerous cells. Antioxidant components are also
believed to promote
restoration of healthy cells and tissue. Neovascular regulators, i.e.,
angiogenesis inhibitors,
are believed to prevent inappropriate vascularization, help regulate growth
factors to deprive
cancerous cells of a blood supply and to inhibit cancer cell proliferation.
Components that
promote collagen synthesis are believed to also inhibit inappropriate
vascularization help
restore growth factors, and to generally restore or promote healthy tissue
thereby inhibiting
metastasis and recurrence of cancers.
Components that regulate blood lipid levels are believed to generally inhibit
cancer
1 S development, growth and recurrence. Components that control blood glucose
levels are also
believed to generally inhibit (directly or indirectly} cancer development,
growth and
recurrence. Components that stimulate the immune response are believed
generally to inhibit
metastasis and cancer recurrence. Components that promote pH balance are
believed to
provide additional protection from cell damage due to oxidative stress.
Components that
inhibit aberrant methylation protect cells from genetic damage and inhibit
carcinogenesis.
Vitamins, minerals and cofactors are generally believed to improve cell and
tissue health and
to help maintain and/or restore normal biochemical function to cells and
tissue and thereby
prevent development, growth and recurrence of cancer. Nutrient components
provided in the
formulas herein are also believed to protect against and/or ameliorate
cachexia which may
result from tumor growth.
Preferred compositions of this invention combine two or more antioxidant
components, two or more neovascular regulators, a component that stimulates or
enhances
collagen synthesis, a component that regulates blood lipid levels, a component
that stimulates
the body's immune response, a component that regulates blood glucose levels
and mineral,
vitamin and cofactor components to supplement deficiencies and help to
maintain and restore
normal cell biochemistry.
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In a specific embodiment, this invention provides preferred protective and
therapeutic
formulas for female cancers including hormone-dependent cancers and cancers
that have a
higher occurrence rates in women (e.g., breast cancer, ovarian cancer, colon
cancer, etc.).
The formulas of this invention can also be combined with components that
ameliorate the
symptoms and conditions associated with osteoporosis.
In another specific embodiment, this invention provides protective and
therapeutic
formulas for the treatment of osteoporosis. These formulas combine
antioxidants,
components that promote collagen synthesis, contribute bone matrix and
structure and inhibit
bone resorption with selected minerals vitamins and cofactors that provide
particular benefit
to ameliorate other symptoms and conditions associated with osteoporosis which
are more
likely to occur in post-menopausal women.
The formulas of this invention, for both cancer therapy and for treatment of
osteoporosis, can be combined wherein indicated in a given individual with
drugs and
compositions for hormone replacement therapy. Formulas of this invention can
be combined
with male hormone supplements where appropriate in a given individual.
This invention also encompasses methods of treatment to prevent or ameliorate
the
symptoms and disease conditions associated with various forms of cancer. These
methods
comprise administration of the compositions of this invention to an individual
suffering from
symptoms or conditions resulting from cancer. Cancer protection methods
comprise
administration of the nutrient compositions of this invention to an individual
desirous of
obtaining such benefit. Methods of this invention can be combined with other
compatible
known methods for cancer treatment, known methods for hormone replacement
therapy and
known methods for treatment of osteoporosis.
DETAILED DESCRIPTION OF THE INVENTION
A description of various components of the formulas of the present invention
follows:
Antioxidants
Antioxidants and antioxidant precursors are included in the compositions of
this
invention to generally combat oxidative stress and resultant genetic damage
and slow the
deterioration of collagen tissues. In general, antioxidants are believed to
protect cells from
cell damage leading to generation of cancerous cells. Further, antioxidants
generally protect
tissue, particularly vascular and capillary tissue, from deterioration, which
is believed to
inhibit metastasis and cancer recurrence. In the more preferred compositions
of this invention
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a complementary antioxidant strategy is employed. Different chemical types of
antioxidants
are combined to provide enhanced antioxidant effect. Preferred antioxidant
combinations
include both hydrophilic (having affinity for water or polar groups) and
hydrophobic (having
an affinity for lipids) antioxidants and combinations of antioxidants from
different natural
plant sources. In a preferred embodiment, antioxidant vitamins (vitamins C or
E), the mineral
zinc and potassium and different plant bioflavonoid sources are combined to
achieve
complementary and synergistic antioxidant effects related to cell and tissue
protection and
healing.
Bioflavonoids containing proanthocyanidins scavenge free radicals and chelate
some
minerals to prevent them from causing oxidation. These bioflavonoids are found
in most
plants from which they can be extracted. Commercially available
proanthocyanidin-
containing plant extracts include: grape seed extract (also called
leucoanthocyanidin), pine
bark extract (including "Pycnogenol" (Trademark, Horphag)), and bilberry
extract. Ginkgo
biloba and other plants which can also provide bioflavonoids, but of generally
lower
proanthocyanidin content, can also supplement antioxidant effect. These
materials and
extracts contain rather complex mixtures of catechins, tannins, oligomers and
proanthocyanidins, at least some of which protect membranes from lipid
peroxidation, and
inhibit superoxides. They are hydrophilic antioxidants, which are many times
more effective
than most antioxidant nutrients at controlling free radicals, superoxides and
lipid peroxides.
Individual plant materials which can provide proanthocyanidins may also
provide other
therapeutic benefits, for example, garlic and willow bark (a source of
salicylic acid) may
provide additional benefit.
Oligomeric proanthocyanidins (OPCs) are polymer chains of 10 or less catechins
which yield red anthocyanidin when boiled in an aqueous solution of 10%
hydrochloric acid.
Proanthocyanidins do not contain condensed tannins but are composed of nearly
60%
catechin forms which have an extremely high affinity for collagen. Catechin
binds tightly to
collagen, modifies its structure by crosslinking and causes it to be resistant
to enzyme
degradation, such as by collagenase, or by lipid peroxidation and superoxide
radicals.
Proanthocyanidins inhibit capillary resistance and capillary permeability and,
thus, improve
vascular damage and deterioration. Collagen accumulates in vessel walls in
endothelia, the
connective matrix, elastin and phospholipids which helps to maintain
structural integrity and
protect these structures from peroxide anion damage. Plant extracts employed
in this
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invention as sources for proanthocyanidins contain varying levels of OPCs.
Antioxidant
effectiveness of an extract generally increases with increasing levels of OPCs
in the extract.
Red wine extract is a source of proanthocyanidins, bioflavanoids (e.g.,
malvidin) and
tannins. Such extracts have antioxidant effect and may function to prevent
platelet
aggregation.
Catechins normally protect cell membranes from lipid peroxidation.
Proanthocyanidins also help to deliver and bind vitamin C to cell sites and
can function to
replace vitamin C at times of ascorbic acid deprivation.
Compositions of this invention can contain one or more sources of
proanthocyanidins
which are included as antioxidants in the formula. Proanthocyanidins also
promote vascular
healing and integrity by restoring the collagen matrix. Different sources of
proanthocyanidins, i.e., plant extracts, can also display other
therapeutically beneficial
functions in compositions of this invention.
Bilberry extract may contain 5 types of anthocyanocides which account for most
of its
activity and 25% of its volume. While bilberry extract inhibits superoxides
and lipid
peroxide to some degree, it is low in oligomeric proanthocyanidins (OPCs) and
therefore is
less effective at controlling these free radical forms than leucoanthocyanidin
(grape seed
extract, for example) described below. Bilberry has an unusual anti-
inflammatory effect,
possibly because it can suppress leukotriene production.
Proanthocyanidins can achieve concentrations in tissue (kidney and skin) up to
5
times the level contained in the bloodstream. High tissue concentrations can
remain up to 24
hours after serum concentrations have been depleted. These factors contribute
to the
protective effect of proanthocyanidins.
The proanthocyanidin-containing extract of grape seeds includes the material
called
leucoanthocyanidin. This commercially available material is obtained from
white grape pips
and is the most effective form of proanthocyanidin, yet discovered, for
inhibiting superoxides
and lipid peroxidation. This is believed to be due to the high level of
oligomeric
proanthocyanidins (OPCs) in the grape seed extract which strongly relates to
vascular
stabilization as described above. Red grape extract which is a good source of
resveratrol can
also be employed in this invention for antioxidant effect and other benefits.
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Pine bark extract, some preparations of which are known by the trade name
"Pycnogenol," is similar to leucoanthocyanidin, having relatively high OPC
levels, but may
possess better ability to suppress phagocytes.
Ginkgo biloba is a "middle range" proanthocyanidin possessing many of the
functional characteristics of both bilberry extract and grape seed extract,
but these active
components are apparently present in lower concentrations. Ginkgo biloba can
cause dilation
of arteries, capillaries and veins and inhibit platelet aggregation. Ginkgo
biloba also
functions to inhibit high blood pressure and would be a preferred ingredient
in formulations
adapted for use by those with hypertension and related disorders.
Green tea extract, tea polyphenols, contains a small amount of 2-3% of
proanthocyanidin. It nevertheless is a potent antioxidant for lipid peroxides,
superoxides and
hydroxyl radicals. It contains relatively high concentrations of (-)
epigallocatechin gallate
(EGCg), a condensed tannin polyphenol. In addition to antioxidant function,
tea polyphenols
also have anti-platelet, anti-cholesterolemia, anti-hypertension, anti-
hyperglycemic and anti-
mutagenic activities. Tea polyphenols also assist theoflavin digallate in
acting as an
angiotensin converting enzyme inhibitor, but do not have the undesired pro-
oxidant
properties of captopril.
Silymarin is an antioxidant bioflavonoid isolated from milk thistle (Silybum
marianum). Silymarin is contains the flavonoid silybin as a major component
and related
compounds silydianin and silychrysin (among others) as minor components.
Silymarin is
typically obtained as a concentrate (80% silymarin) from milk thistle seed
extract. Silymarin
can also be obtained from milk thistle berries. Silymarin is reported to
provide a protective
effect to the liver and is believed to protect liver cells from damage due to
toxins (Ferenci, P.
et al. (1989) J. Hepatol. 9(1):105-113).
Antioxidant bioflavanoids, also include, among others, the flavanone
glycosides
quercitin, naringin, rutin and their aglucons, which are superoxide scavengers
and inhibit
oxidation of LDL. Additional antioxidant bioflavanoids include: curcumin,
kaempferol,
fisetin, ipriflavone, apigenein, coumadin, zingiber, malviden, galangin,
robinetin, myricitin,
hesperiden, taxifolin, morin, deonidin, chrysin, perlargonidin, caffeic acid
any of which can
be included or admixed for additional antioxidant and/or collagen-binding
effect.
Bioflavanoids may also be contained in plant preparations and extracts, e.g.,
nutgall
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(containing tannins and gallic acid), ginger and cinnamon extract. In
preferred antioxidant
combinations, two or more antioxidant bioflavanoids are combined.
The different sources of bioflavonoids, e.g., bilberry, grape seed extract
(leucoanthocyanidin), Ginkgo biloba, pine bark extract ("Pycnogenol"), green
tea extract (tea
polyphenols) and individual bioflavanoids described above have significant
complementary
and synergistic chemical function that in combination with other ingredients
and antioxidants
in the formulas of this invention promote cell protection and repair.
Bioflavanoids can also exhibit other beneficial activities. For example,
quercitin and
ipriflavone may also have benefit in treatment and prevention of osteoporosis.
l0 Supplementation with these bioflavanoids decreases bone resorption and/or
effects bone
development.
Vitamin C or ascorbic acid can be provided in compositions of this invention
in a
variety of forms. Vitamin C is available from a variety of natural sources,
which may also be
employed in the compositions of this invention. Vitamin C is a hydrophilic
antioxidant
generally found in hydrophilic environments in the body, i.e., the
bloodstream, the eye,
interstitial spaces between cells and within cell membranes. It not only
functions as a
scavenger for singlet oxygen and hydroxy radicals, but it also replenishes
spent vitamin E by
replacing electrons. In the bloodstream, vitamin C reduces platelet
aggregation, an anti-
sclerotic effect. Vitamin C, however, has a short half life and may interfere
with diabetic
glucose testing. Forms of vitamin C suitable far use in the formulas of this
invention include
ascorbic acid, isoascorbic acid, ascorbigen, calcium, zinc, magnesium, and/or
sodium
ascorbate, ascorbyl palmitate, and nicotinamide ascorbate. Mixtures of
ascorbate complexes
are also useful in the formulas of this invention to provide a variety of half
lives, differences
in collagen matrix affinity and in matrix building. In addition, combinations
of vitamin C and
cupric sulfate may have direct cell killing action to inhibit tumor growth.
Vitamin C
supplementation can increase bone mass and may have an additional benefit in
osteoporosis.
Indole-3-carbinol is an antioxidant that provides functions similar to that
provided by
vitamin C, however, it is considered to provide protection against a broader
range of
biological oxidation agents.
Vitamin A or retinol or its derivatives and esters thereof are lipid-based
antioxidants
that can be provided in compositions of this invention in a variety of forms.
Vitamin A is
available from various natural sources. Vitamin A can be provided, for
example, as retinol
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palmitate. Vitamin A and derivatives thereof are included in the formulas of
this invention
far their antioxidant function. Vitamin A function can be provided for example
by retinol,
retinal, retinoic acid (particularly 13-cis-retinoic acid and beta-trans-
retinoic acid), and
aromatic retinoids.
Tocopherols (Vitamin E, d-alpha-tocopheryl salts) are hydrophobic, lipid-based
compounds with antioxidant function. They are believed to have a primary role
in protecting
cell membranes from lipid peroxidation. Tocopherols also scavenge free
radicals in the blood
and help to protect Vitamin A and selenium. D-alpha tocopherol forms, the
natural forms of
Vitamin E, are preferred over the less bioactive d,l-tocopherol forms. _
Tocopherols can be
provided in a variety of forms with different counterions. D-alpha-tocopheryl
acetate and
gamma-tocopherol are preferred for use in the compositions of this invention.
Because some
subjects can exhibit a slight rise in blood pressure when Vitamin E is first
taken, smaller more
frequent doses or a time-released form of Vitamin E may be more appropriate
for those
individuals having hypertension or related conditions. Different forms or
derivatives of
vitamin E may exhibit distinct secondary activities, in addition to
antioxidant properties. For
example, vitamin E succinate has been reported to exhibit inhibition of
proliferation of tumor
cells (Kline et al. (1990) Nutrition and Cancer 14:27-41).
Lutien also called xanthophyll, a carotinoid related to beta-carotene, but not
a pro-
Vitamin A carotinoid, is itself a lipid peroxide scavenger and appears to
promote the
production of zeaxanthin, another abundant and powerful lipid-based
antioxidant. Lutien is
an important blood-borne carotenoid strongly related to cardiovascular health.
It is found in
the human retina and is believed to act, possibly in a complementary manner
with zinc, to
protect retinal and macular tissue from oxidative damage. Zeaxanthin, an
isomer of lutein,
isolated from yellow com grits, can be employed in compositions of this
invention in place of
or in addition to lutien.
Beta-carotene is a lipid-based, pro-vitamin A antioxidant which quenches
singlet
oxygen and scavenges free radicals. It plays a role in protecting against
lipid peroxidation.
Beta-carotene may also have a synergistic effect with other carotenoids,
including lutein or
zeaxanthin, for enhanced antioxidant function. Lycopene, canthaxanthin, and
apo-carotenal
are other antioxidant carotenoids that are useful in the formulas herein. In
preferred
antioxidant combinations, two or more carotinoid antioxidants are combined.
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Alpha-lipoic acid (thioctic acid), which can be provided in the acid form or
as an
appropriate Iipoate salt, e.g., sodium lipoate, is an antioxidant and free
radical scavenger that
reacts with reactive oxygen species including superoxide, hydroxyl radical,
hypochlorous
acid, peroxyl radical, and singlet oxygen. Its reduced form, dihydrolipoate,
is also an
effective antioxidant. The d-form is the naturally-occurnng optical isomer and
preferred.
The dl-form is available and can be employed in place of the d-form. Alpha-
lipoic acid and
its reduced dihydrolipoate form can bind to proteins including albumin which
can prevent
glycation reaction.
The mineral zinc, which is discussed in more detail below, is associated with
protection against lipid peroxidation in retinal and epithelial vascular
tissue, possibly due to
its enhancement of superoxide dismutase function. The mineral potassium, also
discussed
below, inhibits superoxide anion.
N-Acetyl-1-cysteine and glutathione are free radical scavengers. N-Acetyl-1-
cysteine
is also very effective for lowering lipoprotein (a} [LP(a)] concentrations in
vivo.
Neovascular Regulators
Normal angiogenesis regulation appears to be accomplished by a variety of
means.
Endogenous factors, e.g., body chemistry, genetics, as well as exogenous
factors, e.g., types
of food consumed, appear to play a role in this important control mechanism. A
number of
substances have been found to affect angiogenesis. Those substances that
inhibit or moderate
undesired angiogenesis are preferred for use in the compositions of this
invention. Preferred
compositions of this invention comprise more than one chemical type of
angiogenesis
regulator or more than one source of an angiogenesis regulator. Different
regulators are
believed to function in a complimentary manner to achieve a biochemical
balance. In
addition, components of the compositions, other than specifically listed
neovascular agents,
may also affect angiogenesis. For example, antioxidants and free-radical
scavengers can
control free radicals which, by various mechanisms, may destroy angiogenesis
regulation.
The control of oxidative stress due to antioxidants may have a significant
effect on beneficial
neovascular control. As discussed above regarding antioxidants, conservative
doses of
several angiogenic regulators are believed to be more beneficial, i.e.,
enhanced effectiveness
with minimal potential for toxic effect, than larger doses of a single
chemical.
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Cartilage, an avascular tissue, is a source of angiogenesis inhibitor(s).
Shark and
bovine cartilage, among others, are sources of angiogenesis inhibitor and may
provide
collagenase inhibition as well. Chondroitin sulphate, a mucoploysaccharide
found in most
mammalian cartilaginous tissues and shark cartilage, is believed by many to be
the most
active angiogenesis regulating component of shark cartilage. The restoration
of depleted
chondroitin sulphates may also affect collagen stabilization which would help
to normalize
the collagen matrix of vascular tissue and therefore create a more stable
vascular structure.
Chondroitin sulphate can be provided in a number of forms with different
counterions, e.g.,
sodium, potassium, etc. Sodium chondroitin sulphate is the form preferred for
use in
compositions of this invention.
Protamine sulphate is a mixture of the sulphates of basic peptides that can be
prepared
from the sperm or the mature testes of certain species of fish. It is an
arginine rich basic
protein which has been shown to be a specific inhibitor of angiogenesis,
possibly due to its
ability to bind to heparin. Protamine has been used in some insulin
preparations to prolong
the effects of insulin. Protamine is usually given as the sulphate, but the
hydrochloride form
may also be used.
Genistein as well as daidzein are plant-derived isoflavonoids found, for
example, in
soybeans, that exhibit an ability to inhibit neovascularization by controlling
endothelial cell
proliferation in vitro. Soy isolate is a natural source of genistein, daidzein
or the glycoside
derivatives (e.g., genistein, daidzein and sophoricoside) of these
isoflavones. Soy isolate also
provides nutritional benefit and may supplement depleted amino acids.
Additional plant-
derived isoflavonoids include kievitone. Genistein and possibly kievitone may
also function
as a tyrosine kinase inhibitor causing apoptosis in certain cancer cells.
Certain plant derived
isoflavonoids, such as genistein, exhibit estrogenic function. Such
isoflavonoids can
function, like estrogen, to inhibit bone loss. Phytosestrogen, particularly
those isolatable
from soy, can have inhibitory effects upon cancer.
Gymnema sylvestre which normalizes heparin levels is provided in the
compositions
of this invention, at least in part, to affect heparin levels which in turn
may affect angiogenic
regulation due to shark cartilage and protamine sulfate which both bind to
heparin. The
Gymnema sylvestre also provides for insulin/glucose stabilization which can
further reduce
the oxidative stress that contributes to the neovascularization factors
described above.
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Garlic extract (allicin), licorice extract (glyzzeryn), ginger, red wine
extract, citrus
pectin and/or marine tunicates can function for neovascular regulation and may
provide
additional therapeutic or nutritive benefit.
Collagen Factors
Maintenance and restoration of the collagen matrix in vascular and other
tissue,
especially as a means to stabilize and regulate growth factors, is an
important aspect of the
formulations of this invention. In this regard, building blocks for collagen
synthesis, growth
regulators related to collagen synthesis and repair, cofactors for synthesis
of collagen,
calcium binding and/or regulatory agents and nutrients including various
minerals associated
with promotion of collagen synthesis are provided in formulas of this
invention.
Glucosamines stimulate and provide building blocks for collagen synthesis.
Chondroitin
sulphate is a flucosamine that functions for growth regulation and stimulates
collagen
synthesis. Glucosamine sulphate is a preferred glucosamine for promoting
collagen synthesis
and repair.
Manganese is a cofactor which promotes collagen synthesis. Amino acids,
particularly branched chain amino acids (L-leucine, L-isoleucine and L-
valine), provide
protein for synthesis of collagen.
Other components that affect collagen synthesis are inhibitors of mammalian
collagenases and antioxidants. Inhibition of collagen breakdown by oxidative
stress or by
enzymatic degradation combined with stimulation and promotion of collagen
synthesis is
believed to result in improved collagen matrix.
Minerals
The compositions of the present invention include various minerals including
zinc,
chromium, calcium, magnesium, potassium, manganese, and selenium. Other
minerals
which may have beneficial or nutritional value for a given individual,
particularly those
minerals that are depleted can be provided individually or as a mineral
complex. Certain
minerals can have additional therapeutic value in the compositions of this
invention. For
example as discussed above, zinc is believed to play a significant role as an
antioxidant.
In general, minerals can be provided in a variety of forms with various
counterions.
The choice of a given form of mineral will depend generally on the type of
dosage form that
is employed, whether, for example, an oral or intravenous dosage form is
employed.
Preferred forms of minerals are generally those that are more absorbable and
those that have
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lower toxicity. In addition, preferred forms will be generally compatible with
the other
components of a given mixture, will result in minimal irntation or other
undesired side
effects. Choices of form of a given mineral provided in a given composition of
this invention
will also depend on the other ingredients in the composition, particularly to
avoid excessive
levels of a given counter ion.
Zinc can be provided in a variety of forms and with various counter ions,
including
among others zinc citrate, zinc fumarate, zinc gluconate, zinc alpha-
ketoglutarate, zinc
lactate, zinc malate, zinc succinate, zinc picolinate or mixtures thereof. The
preferred form of
zinc in the compositions of this invention is zinc (Krebs) in which the
counter ions are a
mixture of the anions of the five primary organic acids of the tricarboxylic
acid cycle (Krebs
Cycle) i.e., a mixture of the zinc salts of citric, fumaric, malic, alpha-
ketoglutaric and succinic
acids. Zinc may have an indirect effect on bone resorption by inhibiting
cadmium
accumulation.
Chromium can be provided by a variety of dietary sources including, among
others,
brewer's yeast, liver, potatoes with skin, beef, fresh vegetables and cheese.
Chromium exists
in a dinicotino-glutathionine complex in natural foods. Such dietary and
natural materials
can provide sources of chromium for use in compositions of this invention. As
with other
minerals, there are generally a variety of forms of chromium that are useful
in the
compositions of this invention including, for example, chromium sulphate.
Chromium
nicotinate (Chromium-nicotinic acid complex) is a preferred form of chromium
for use in the
formulas of this invention. Chromium picolinate can be employed in the
formulas of this
invention, but is not generally preferred. Chromium enhances insulin activity
and as a result
can affect blood lipids. For example, chromium nicotinate acid complexes can
lower blood
triglyceride levels. Chromium also decreases calcium excretion.
Magnesium can be provided in a variety of forms and with various counter ions,
including among others magnesium citrate, magnesium fumarate, magnesium
gluconate,
magnesium alpha-ketoglutarate, magnesium lactate, magnesium malate, magnesium
succinate, magnesium picolinate, magnesium sulphate or mixtures thereof.
Preferred forms
of magnesium in the compositions of this invention are magnesium citrate,
magnesium
malate, magnesium malate-citrate, and magnesium (Krebs) in which the counter
ions are a
mixture of the anions of the five primary organic acids of the tricarboxylic
acid cycle (Krebs
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Cycle) i.e., a mixture of the magnesium salts of citric, fumaric, malic, alpha-
ketoglutaric and
succinic acids. Magnesium deficiency may be a risk factor in osteoporosis.
Calcium can be provided in a variety of forms and with various counter ions,
including among others calcium ascorbate, calcium carbonate, calcium citrate,
calcium
fumarate, calcium gluconate, calcium alpha-ketoglutarate, calcium levulinate,
calcium lactate,
calcium malate, calcium succinate, calcium picolinate or mixtures thereof.
Calcium can also
be provided in a variety of natural sources including dolomite, oyster shells,
and bone meal.
The more preferred form of calcium in the compositions of this invention is
calcium (Krebs)
in which the counter ions are a mixture of the anions of the five primary
organic acids of the
tricarboxylic acid cycle (Krebs Cycle) i.e., a mixture of the calcium salts of
citric, fumaric,
malic, alpha-ketoglutaric and succinic acids. Also preferred for use in
compositions of this
invention are calcium carbonate, calcium citrate, and calcium malate-citrate
which are noted
for being highly absorbable.
Calcium is an important component of osteoporosis formulas increasing bone
mass
and decreasing bone fragility. Strontium, in low doses, reduces bone
resorption and maintains
high bone formation. Boron is included in osteoporosis formulas herein to
balance in vivo
potassium and calcium levels.
Potassium can be provided in a variety of forms and with various counter ions,
including among others potassium citrate, potassium carbonate, potassium
fumarate,
potassium gluconate, potassium alpha-ketoglutarate, potassium lactate,
potassium malate,
potassium succinate, potassium picolinate or mixtures thereof. The preferred
form of
potassium in the compositions of this invention is potassium citrate which has
one of the
highest levels of elemental potassium.
Manganese, selenium, and strontium can be provided in a variety of forms with
various counterions. Selenium is preferably supplied as an organoselenium
compound, e.g.,
selenomethionine. Manganese aspartate is a preferred form of manganese for use
in the
formulas of this invention.
Ranges of zinc (Krebs}, calcium (Krebs), magnesium (Krebs), chromium
nicotinate,
potassium citrate and other minerals in an average daily dose of a composition
of this
invention are provided in Table 2. The ranges given are maximum ranges which
may need to
be adjusted dependent upon the amount and form of other ingredients included
in the
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composition. These ranges can be readily adjusted by those of ordinary skill
in the art of
nutrient and therapeutic formulation to other forms of the minerals noted
above.
A mineral complex can optionally be combined with the compositions of this
invention in addition to or substituted for specific minerals in the various
formulas.
Preferably, the mineral complex is used to supplement nutritional minerals not
already
included in specific formulation. A preferred mineral complex includes
absorbable salt or
chelated forms of:
major mineral components: calcium, magnesium, and potassium also chloride
(e.g., as
potassium chloride) and sulphate (e.g., as manganese sulphate);
intermediate level components: zinc, manganese, boron and copper;
minor components: chromium, selenium, iodine, molybdenum, vanadium, lithium,
rubidium, silicon (as silica), nickel, phosphorus, strontium and cadmium;
trace minerals: preferably from natural sources e.g., marine organic minerals
or sea
water concentrate.
The minerals may be provided in a variety of salt and complex forms, i.e., as
the salts
of Krebs cycle acid anions: aspartate, citrate, fumarate, malate and/or
succinate salts; as salts
of amino acids (e.g., arginates); as picolinate salts; as ascorbate salts, as
nicotinate salts.
Silicon is preferably provided as the trisillicate anion, e.g., magnesium
trisillicate. Selenium
is preferably provided as organoselenium compound, e.g., selenomethionine. A
variety of
natural sources of minerals are known to the art including plant extracts, and
can be used to
provide minerals in the formula of this invention. A preferred mineral complex
provided in
Table 1.
Minerals specifically included in a given formulation of this invention are
preferably
provided at the level indicated in that formulation. For an individual
diagnosed with a
particular mineral deficiency (e.g., iron deficiency), dosages of a given
mineral may be
increased as needed and additional minerals, e.g., iron, may be added to the
mineral complex.
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TABLE 1: MINERAL COMPLEX COMPONENTS
Calcium (Krebs) (lactate, aspartate, argininate10 m to 10,000
etc.) m
Magnesium (Krebs),( aspartate, argininate, 3 mg to 10,000
triscilicate (malate), mg
etc.
Potassium Krebs (ar inmate, as artate 2 m to 10,000 m
Zinc Krebs) icolinate) 1 m to 100 m
Man anese (Krebs) 10 me to 100 m
Boron ( luconate) ' 0 me to 100 m
Co er (Krebs) 10 me to 50 m
Chromium icolinate, nicotinate, etc.) 2 me to SO m
Selenium (1-selenomethionine) 1 me to 50 m
Iodine marine or anic minerals, kel , etc.) 1 me to 50 m
Mol bdenum Krebs) 1 me to 50 m
Vanadium Krebs) 1 me to SO m
Lithium as artate, ar inmate, etc. 1 me to 50 m
Rubidium Krebs 1 me to 50 m
Silica sodium melasilica, ma esium trisilicate10 me to 200 m
Trace minerals marine or anic minerals 10 me to 200 m
Cobalt 10 me to 200 m
Nickel 1 me to SO m
Phos horns (e. ., dicalcium hos hate) 1 me to 50 m
Chloride (e. ., otassium chloride) 1 m to 1,000 m
Sul hur (man anese sul hate) 10 me to 100 m
Strontium 1 me to 800 m
Cadmium 1 me to 500 m
Vitamins
Vitamins are included in compositions of this invention to provide
supplementation
for depletion and dietary deficiencies and in some cases for specific
therapeutic benefits.
Vitamins may also complement the activity of other components of the
composition.
Vitamin C, i.e., ascorbic acid, vitamin E, i.e., alpha-tocopherol, and vitamin
A provide
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general nutritional supplementation as well as antioxidant function, as
discussed above.
Vitamin B6, i.e., pyridoxine, vitamin B 12, i.e., cobalamine, and folic acid
(folate) provide
general nutritional supplementation, and more specific benefits. Folate and
vitamins B6 and
B12 have antianemia properties. Folic acid decreases homocysteine levels.
Vitamin B2, i.e.,
riboflavin, provides general nutritional supplementation. Vitamin B6
deficiency may
detrimentally effect bone formation. Vitamin D can provide positive beneficial
effect in
protection and/or inhibition of cancer. A preferred form of vitamin D is
vitamin D3.
A vitamin B complex can be employed in addition to or substituted for Vitamin
B
components of the formulas of this invention. A preferred Vitamin B complex
includes:
Vitamin Bl (thiamine) lOpg - 100 mg (10%))
Vitamin B2 (riboflavin) l Opg - 50 mg (5%)
Vitamin B3 (nicotinamide or niacinamide,
preferably as niacinamide ascorbate) 1 mg-1,000 mg (53%)
Vitamin BS (pantothenic acid) 1 mg -200 mg (26%)
Vitamin B6 (pyridoxine HCl) lOpg - 3 mg (5%)
Vitamin B12 (cyanocobalamin) 1 p,g - 200 wg (0.03%),
where a preferred range and preferred specific relative amounts of the
components are given.
Amino Acids
The formulas of this invention include amino acids that have a particular
therapeutic
function. Formulas of this invention may also contain additional amino acids
for nutrient
supplementation or for compensation for an individual's deficiency.
Compositions of this
invention can include any of the following: alanine, arginine, aspartic acid,
cystine, glutamic
acid, glycine, histidine, isoleucine, leucine, lysine, methionine,
phenylalanine, proline, serine,
threonine, tryptophan, tyrosine, valine, carnitive (all in the biologically
active L-form) and
gamma aminobutyric acid. When present in a given formula, a specifically
listed amino acid
is preferably provided in the amount needed to provide the desired therapeutic
effect.
Additional nutritional amino acids are preferably provided in an nutritionally
effective
amount.
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Lysine
Supplementation of amino acid deficiencies is generally important to maintain
normal biochemical function. Amino acid deficiencies, particularly lysine
deficiency, can
reduce calcium utilization. Lysine is provided in formulas herein to avoid
such deficiency
S and enhance calcium utilization, particularly in osteoporosis formulas.
Methionine/Cysteine
Aberrant methylation can result in DNA damage, mutation and result in
cancerous
cells. Maintenance of normal methionine metabolism, for example by
supplementation with
methionine or cysteine, may avoid DNA damage and insure DNA repair. Normal
methionine
metabolism may also be promoted by supplementation with folic acid, choline
and betaine.
Arginine may function as a non-specific immune modulator stimulating immune
response.
Glutamine deficiency may occur in patients with cancerous tumors due to
significant
consumption of glutamine by the tumor. Glutamine is provided in formulas
herein to
compensate for deficiency.
Branched amino acids (leucine, isoleucine and valine) are benef cial in
collagen
maintenance and synthesis providing protein components for collagen synthesis.
Other components:
Sulforaphane is an isothiocyanate derived from Cruciferae. This material is
reported
to inhibit development of cancer by inducing detoxifying phase 2 enzymes
(Raloff, J. (1997)
Science News 152:183). Broccoli sprout extracts are a good source of
sulforaphane.
Fenugreek (Tigonella foenumgraecum L. Leguminous) is an annual herb, the seeds
of
which contain a number of alkaloids, including trigonelline and coumarin, and
the steroidal
sapogenin, diosgenin. Fenugreek provides phytoestrogens. Fenugreek seeds
reduce serum
cholesterol levels in animals. In particular, the defatted fraction of
fenugreek seed which is
rich in fiber (about 54%) and contains about 5% of steroidal sapogenin,
including diosgenin
significantly lowers plasma cholesterol, blood glucose and plasma glucagon
levels.
Fenugreek is included in certain preferred compositions of this invention for
control of blood
glucose levels. The preferred form of fenugreek for formulations of this
invention is the
defatted, fiber-rich fraction.
Terpenes/monoterpenes and metabolites thereof can exhibit inhibition of cancer
cell
growth. The effect may result from inhibition of enzymes needed for cell
growth. Limonene
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(d-limonene), narigninen, tangeritin, nobelitin, iberene and d-carcone are
exemplary
monoterpenes. D-limonene is a preferred monoterpene for use in the formulas of
this
invention.
Source of omega-3-fatty acids
Omega-3 oils are a family of oils having relatively high concentrations of
omega-3
polyunsaturated fatty acids, including eicosapentaenoic acid (EPA) and alpha-
linolenic acid.
These oils exhibit a hypolipidaemic action, especially a reduction in plasma
triglycerides
linked to a reduction in very-low density lipoproteins (VLDL). They also
exhibit anti-
inflammatory effects. Fish oils and other marine oils typically contain high
levels of omega-
3-fatty acids. In general, omega-3-fatty acids are believed to reduce blood
pressure, and
lower cholesterol and triglyceride levels. Omega-3 fatty acids are found in a
variety of
naturally-occurring sources and may be provided in their acid form or as fatty
acid salts or
fatty acid esters.
Chronic omega-3-fatty acid deficiency correlates with chronic nephropathic
injury.
EPA and DHA (docosahexanoic acid) produce an anti-inflammatory effect by
reducing
prostaglandin production and displacing arachidonic acid. HDL, triglycerides
and fibrinogen
have also been successfully reduced by omega-3-oils. Omega-3-fatty acids are
included in
formulas herein, at least in part, for their function in the control of blood
lipid levels.
Flaxseed (also called Linseed) is a nutrient rich in omega-3-fatty acids. It
is a major
source of alpha-linolenic acid (an omega-3-fatty acid) and lignin. Ground
flaxseed is a
preferred source of omega-3-fatty acids over fish oils for use in compositions
of this
invention. The use of flaxseed oils, particularly in cases where the formula
is being used
chronically for protective or prevention benefit, avoids the potential
toxicity that has been
associated with long term use of fish oils. Fish and marine oils or individual
omega-3-fatty
acids, including EPA, and ALA (and their analogous fatty acid esters) can be
used in these
formulations in place of flaxseed. Omega-3 fatty acids may have a protective
effect against
tumorogenesis.
Essential fatty acids (EFAs) are those fatty acids that cannot be made by the
body
and must be supplied through the diet. Fresh, poly-unsaturated vegetable oils
are a major
source for EFAs (linoleic, linolenic and appropriate levels of arachidonic
acids). EFAs have
a variety of beneficial effects including reduction of blood pressure, lower
cholesterol, and
lower triglyceride levels. Linolenic acid is one essential fatty acid for
formulations of this
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invention. A natural source of linolenic acid is Evening Primrose Oil which
also provides
high levels of GLA (gamma-linoleic acid, about 9%) with minimal toxic
properties.
Conjugated dienoic linoleic acid is a particularly preferred derivative of
linoleic acid which
may provide protection from oxidation that can lead to cell damage, mutation
and
carcinogenesis.
Coenzyme Q,o, also designated ubiquinone(50) is one of a group of
benzoquinones
involved in electron transport. Coenzyme Qn, where n = 1-12, has a 2,3-
dirnethoxy-5-
methylbenzoquinone nucleus with various terpenoid side chains. Coenzyme Q with
10
isoprene units (Coenzyme Quo) is the most common form in animals. Coenzyme Qn,
where n
= 6-10, are naturally occurring. Coenzyme Q,o is a necessary component of the
energy-
generating process of every cell in the body. Coenzyme Q,o can also function
as an
antioxidant. Coenzyme Q,a, the preferred form of coenzyme Q for human
nutrition and
therapy, is provided in formulations of the present invention to supplement
nutritional
deficiencies which are believed to generally exacerbate disease conditions.
Adequate tissue
reserves of Coenzyme Q,o may also facilitate blood sugar regulation. Coenzyme
Q,o is also
believed to generally enhance an individual's energy levels. Other forms of
coenzyme Q,
particularly coenzyme Q", where n is 1-9 and 10-12 and more preferably the
naturally-
occurnng forms where n = 6-9, can be employed along with or in place of
coenzyme Q,o in
the formulas of this invention.
Taurine is found in high concentrations in the brain, retina and kidney
cortex.
Taurine may have a protective effect on tissue and/or act as an antioxidant.
Taurine has also
been linked to inhibition of platelet aggregation and atherosclerotic lesions
and has been
found to help control blood pressure. Taurine can be provided from a variety
of sources in
different forms. Homotaurine, a taurine precursor, is a good bioavailable oral
form to provide
taurine. Compositions herein can contain taurine or homotaurine. Taurine
appears to affect
calcium levels and is included in osteoporosis formulas.
L-Carnitive is an essential co-factor of fatty acid metabolism. Faulty
transport of
fatty acids across mitochondrial membranes may lead to oxidative stress due to
reduced lipid
metabolism. Carnitive supplementation supports increases in fat utilization
and oxygen
uptake while decreasing plasma lactate levels and respiratory quotients.
Carnitive has been
shown to reduce ketones, LDL and triglycerides and increase HDL while acting
as a
vasodilator. L-Carnitive can be provided as N-acetyl-1-carnitive
hydrochloride, the preferred
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form for this invention. Carnitive can be also be provided as the 1- or d,l-
form as
hydrochloride or other salts.
Sesamin/Sesamolia are constituents of sesame oil and/or sesame seeds. These
components are believed to affect blood lipid levels.
Phytosterols, including plant sterols, which comprise beta-sitosterol,
campesterol,
and/or stigmasterol have been shown to reduce the absorption of the LDL
cholesterol
component of foods in the gut on a dose dependent basis of approximately one-
to-one sterols
to cholesterol, while enhancing beneficial HDL to positively effect the LDL-
HDL Ratio.
Plant sterols have been shown to primarily block harmful LDL cholesterol and
admit
beneficial HDL cholesterol, the levels of which can actually be elevated.
Plant sterols can be
provided in the formulas of this invention in soy oil or by addition of
individual sterol
components. A commercially available mixture of phytosterols, "Cholestatin
III" (about 62%
beta-sitosterol, about 24% campesterol and about 14% stigmasterol}, produced
in bacterial
fermentation, is preferred for use in the formulas of this invention. Saw
palmetto is another
1 S useful source of phytosterols.
Gymnema sylvestre
Gymnemic acid, the active ingredient in gymnema sylvestre, suppresses
sensitivity to
sugar and its absorption, thereby reducing blood glucose levels. It also
restores the levels of
three chondroitin sulfates which may assist in collagen repair and/or aid in
angiogenesis
regulation. Heparin sulphate levels are increased in diabetics while three
chondroitin sulfates
are decreased. Gymnema sylvestre which normalizes heparin levels could play a
supporting
role in the angiogenic regulation of other ingredients in this formulation,
namely shark
cartilage and protamine sulfate. Both are angiogenic regulators which bind to
heparin. The
restoration of depleted chondroitin sulfates probably plays a role in collagen
stabilization
which would help to normalize the collagen matrix and therefore create a more
stable
structure upon which angiogenesis regulation could more easily exist. The
insulin/glucose
stabilization effects of Gymnema sylvestre would reduce the oxidative stress
that contributes
to the neovascularization factors described above.
Garlic/Garlic Extract
Alicin and garlicin are active ingredients of garlic and garlic preparations
that have
been associated with control of blood glucose levels, cholesterol reduction
and triglyceride
reduction. These materials are included in the formulas herein for their
general inhibitory
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activity against cancer. Dried powder and extract of Allium species
(particularly garlic) can be
employed to provide these functions.
Chlorophyll is the green pigment of plants found in both higher plants and
algae.
Dependent upon plant/algal source chlorophyll can contain mixtures of
chlorophyll a, b, c or
d. A variety of commercial chlorophyll preparations are available for use in
the formulas
herein. Chlorophyll is employed in the formulas herein to reduce the effect of
carcinogens
and inhibit carcinogenesis.
Chinese Herbs. The herbs Oldenlandia diffusa, Scutellaria barbata, Astragalus
membranaceus, and Ligustrum lucidum are used in traditional Chinese medicine
as adjuncts
to cancer therapy.
Calcitonin (Merck Index, Ninth Edition (1976) 1633 P.208) is a calcium
regulating
hormone secreted by mammalian thyroid gland that is employed in the treatment
of bone
disorders including osteoporosis. Amylin (see U.S. patent 5,405,831 ) is a
peptide found in
amyloid deposits of diabetics (Type 2), which may be a peptide hormone having
a role in
storage and disposal of food as carbohydrate and fat. Amylin increases liver
output of
glucose, increases lactate production in muscle and decreased insulin action.
US 5,405,831
reports that amylin, variants of amylin and amylin agonists are useful, like
calcitonin, for the
treatment of bone disorders to prevent or inhibit bone resorption because of
its role in calcium
metabolism.
Fluoride/Sodium Fluoride
Calcium provided in combination with slow release sodium fluoride can inhibit
development of fractures. Sodium fluoride is provided in osteoporosis formulas
herein.
Other forms of fluoride may provide similar benefit.
Vitamin D3 is associated with calcium transport and bone calcium resorption.
1,25-
dihydroxy vitamin D3 is reported to increase calcium absorption, lower blood
pressure and
increase sensitivity to insulin. Certain analogs and derivatives of 1,25-
dihydroxy vitamin D3
are reported to induce minimal or no hypercalcemia. (Hypercalcemia is a
significant
contributing factor to the toxicity of vitamin D's.) A vitamin D derivative,
22-oxa-vitamin
D3, is thus indicated to have reduced toxicity compared to vitamin D3. See:
Abe, J. et al.
(1991)Endrocrinology 129:832-837 and Mark, R. (1992) Pediatric Nephrology
6:345-348.
Vitamin D3 is also reported to be important in cell differentiation. The
inventor includes
vitamin D3, particularly lower toxicity Vitamin D3 analogs (22-oxa-Vitamin D3)
in the
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formulas of this invention as a calcium regulator that is a factor for
promotion of collagen
synthesis and more importantly for its additional function in stimulating or
enhancing
immune response. Vitamin D3, preferably 22-oxa-vitamin D3, is also provided in
osteoporosis formulas herein.
Vitamin K
Vitamin K is a cofactor involved in blood coagulation. Vitamin Kl, or
phylloquinone, is a preferred form of Vitamin K for use in the formulas
herein. Vitamin K is
also reported to increase calcium binding affinity of certain proteins in bone
formation.
Vitamin K is included in formulas of this invention to supplement any vitamin
or cofactor
deficiency and for its calcium-binding function which indicates usefulness in
tissue
regeneration and benefit for osteoporosis.
Melatonin, a hormone, provides for inhibition of prolactin which is a
stimulator of
growth of breast cancer cells. Melatonin thus provides indirect inhibition of
cancer cells.
Betaine HCI, Pepsin and Sodium Bicarbonate
Inappropriate acidity is believed to be a factor in the pathogenesis of
chronic disease.
Mitochondrial antagonism resulting in oxidative stress is a probable
mechanism. Betaine
HCI, pepsin and sodium bicarbonate have all demonstrated the ability to help
regulate
hyperacidity. In addition, betaine HCl and pepsin are among digestive enzymes
often
deficient in the elderly as well as chronic disease sufferers. Betaine may
also effect
methionine metabolism to provide protection from DNA damage due to aberrant
methylation.
Inappropriate acidity may result in bone dissolution. Factors that control
acidity can provide
benefit in osteoporosis and are included in osteoporosis formulas herein.
Specific cancer preventative and therapeutic formulas of this invention
include:
Formula I which comprises:
(i) antioxidants selected from:
(a) a plant extract having antioxidant effect comprising
bioflavanoids, particularly an extract providing a major source
of proanthocyanidins, such as bilberry extract, grape seed
extract, or pine bark extract. Bioflavanoids of lower
proanthocyanidin content, for example, ginkgo biloba, can also
be used to supplement major sources; combinations of plant
materials and extracts can also be employed;
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(b) antioxidant vitamins, e.g., vitamin C and/or vitamin E;
(ii) tea polyphenols providing for additional antioxidant benefit;
(iii) absorbable zinc, preferably zinc(Krebs) to supplement dietary
deficiency; which may be provided in a mineral complex;
(iv) a neovascular regulator selected from genistein, kievitone, daidzein or
a related isoflavonoid, and chondroitin sulphate or cartilage;
Isoflavonid may be provided as soy isolate comprising genistein and/or
daidzein; Genistein is the preferred isoflavonoid; and
2. Formula II which comprises:
(i) antioxidants including the bioflavanoids: pine bark extract (preferably
high OPCs, e.g., 85% or greater oligomeric proanthocyanidins
(OPCs)); and bilberry extract (preferably low OPCs, e.g., 25%
oligomers OPCs); and the antioxidants: vitamin A and vitamin E;
(ii) tea polyphenols;
(iii) absorbable zinc;
(iv) genistein (optionally provided in soy isolate) and chondroitin sulphate
(optionally provided in a cartilage preparation);
(v) arginine which may be provided in an amino acid complex.
3. Formula III which comprises:
(i) pine bark extract, bilberry extract, grape seed extract
(leucoanthocyanidin), and ginkgo biloba;
(ii) vitamin C, vitamin E and vitamin A;
(iii) monoterpene, e.g., limonene;
(iv) antioxidant carotenoids, e.g., beta-carotene, lutein, lycopene, luteolin,
zeaxanthin or apo-carotenal (beta-carotene being preferred);
(v) tea polyphenols;
(vi) absorbable zinc, calcium (e.g., calcium citrate, calcium malate or
calcium maltate citrate) and magnesium (e.g., magnesium citrate,
magnesium malate or magnesium malate citrate);
(vii) genistein and chondroitin sulphate;
(viii) L-arginine or amino acid complex; and
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(ix) a source of omega-3 fatty acids, particularly conjugated dienoic fatty
acids, e.g., linoleic acid (ALA) and/or enosapentaenoic acid (EPA), a
preferred source is ground flax seed;.
4. Formula IV which comprises:
The components of Formula III; and
protamine sulphate and/or glucosamine sulphate (a preferred
glycosaminoglycan and source of glycosamine, a building block for collagen
synthesis);
vitamin D3, preferably derivatives thereof which induce little or
substantially
no hypercalcification (e.g., 22-oxa-vitamin D3); and
branched amino acids.
5. Formula V which comprises:
The components of Formula IV and
quercitin;
Saw palmetto;
vitamin B 12 and folic acid (or optionally vitamin B-complex);
absorbable potassium and selenium;
alpha-lipoic acid (also called thiotic acid); and
allicin (or garlic extract);.
Formula SA which comprises the components of Formula 5 where the
antioxidant carotenoids are a mixture of beta-carotene and lutein.
Formula SB which comprises the components of Formula 5 which contains a
mixture of chondroitin sulphate, protamine sulphate and shark cartilage and
where the antioxidant carotenoids are a mixture of beta-carotene and lutein.
6. Formula VI which comprises:
The components of Formula V, SA or SB and
silymarin;
curcumin;
niacinamide;
a source of essential fatty acids, particularly conjugated dienoic fatty
acids; for
example, linoleic acid and
one or more of sodium bicarbonate, betaine HCI or pepsin.
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Formula 6A comprises the components of Formula 6 and contains a mixture of
chondroitin sulphate, protamine sulphate, glucosamine sulphate and optionally
shark or animal (e.g., bovine) cartilage.
Formula 6B comprises the components of Formula 6 and contains a mixture of
$ the monoterpenes limonene and naringinen and a mixture of the carotenoids
beta-carotene, lutein and lycopene.
7. Formula VII which comprises the components of Formulas VI, A or B and
absorbable chromium;
resveratol;
I 0 kaempferol;
sesamm;
melatonin; and
coenzyme Q, particularly coenzyme Q~p(CoQlO).
Formula 7A comprises the components of Formula 7 and contains a mixture of
I S chondroitin sulphate, protamine sulphate, glucosamine sulphate and a
cartilage
preparation (shark and/or bovine cartilage).
Formula 7B comprises the components of Formula 7 and contains a mixture of
genistein and kievitone.
8. Formula VIII which comprises:
20 The components of Formulas VII, 7A or 7B and
Gymnema sylvestre;
biotin;
garlicin;
chlorophyll;
2$ glutathione; and
a source of taurine.
Formula 8A comprises the components of Formula VIII and contains a
mixture of carotenoids including beta-carotene, lutein, lycopene, and
luteolin.
Formula 8B comprises the components of Formula VIII and contains a
30 mixture of monterpenes including limonene, naringinen, and tangeritin.
9. Formula IX which comprises
26
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The components of Formulas VIII, 8A or 8B and
cinnamon extract;
absorbable copper;
indole-3-carbinol;
fenugreek seed (preferably defatted powder);
N-acetylcysteine;
pectin, e.g., citrus or apple pectin;
betaine HCl and pepsin.
Formula 9A comprises the components of Formula IX containing a mixture of
monoterpenes: lirnonene, naringenin, tangeritin and nobelitin.
10. Formula X which comprises:
The components of Formula IX or 9A and
coumarin;
zingiber;
1 S ginger;
absorbable boron;
vitamin K1;
sesamolin; and
methionine.
Formula l0A comprises the components of Formula X and contains a mixture
of monoterpenes including limonene, naringinen, tangeritin, nobiletin, and
iberene.
Formula lOB comprises the components of Formula X wherein the source of
omega-3 fatty acids is a fish oil.
11. Formula XI which comprises:
The components of Formula X, l0A or l OB and
nutgall; malviden; galangin; robinetin; myricitin;
absorbable manganese;
alpha-linoleic acid; and
lysine.
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Formula 11A comprises the components of Formula XI and contains the
mixture of carotenoids beta-carotene, lutein, lycopene, luteolin, and apo-
carotenal.
Formula 11B comprises the components of Formula XI and contains a mixture
of apple and citrus pectins.
12. Formula XII comprises the components of Formulas XI, 1 lA or 11B and:
hesperiden;
rutin;
taxifolin;
monn;
absorbable strontium;
gamma-linoleic acid;
glutamine; and
dried mushroom or mushroom extract, e.g., shitake or rieshi.
Formula 12A comprises the components of Formula X and contains a mixture
of monoterpenes including limonene, naringinen, tangeritin, nobiletin,
iberene, and d-carvone.
13. Formula XIII comprises the components of Formulas XII and 12A and
denonidin;
chrysin;
perlargonidin;
caffeic acid;
absorbable silicon; and
glyzzeryn (or licorice extract)
Formula 13 A comprises the components of Formula XIII and contains a
mixture of genistein and daidzein.
In a specific embodiment, nutrient and therapeutic formulas for use in the
treatment of
female cancers, including hormone-dependent cancers are provided. Female
cancers include
those cancers that occur only in women or which are more prevalent in women,
including
breast and ovarian cancer as well as cancer of the colon.
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Specific formulas for the treatment of female cancers include:
14. Formula XIV which comprises:
(i) Antioxidants:
A source of proanthocyanidins and/or bioflavanoids (e.g., pine bark
extract, bilberry extract, etc.);
A neovascular regulator (e.g., genistein, cartilage, etc.);
vitamin C;
vitamin E;
vitamin A;
beta-carotene;
(ii) Vitamin D3; and
(iii) calcium.
15. Formula XV which comprises the components of formula XIV and
selenium;
folic acid;
omega-3/omega-b fatty acids (flax seeds or fish oil); and
soy isolate containing phytoestrogens and/ or phytosterols (phytoestrogens can
be
replaced with soy isoflavones, such as genistein or daidzein).
16. Formula XVI which comprises the components of formula XV and
melatonin;
lycopene; and
shark or bovine cartilage.
17. Formula XVII which comprises the components of formula XVI and
limonene;
arginine; and
conjugated dienoic linoleic acid.
18. Formula XVIII which comprises the components of formula XVII and
curcumm;
niacin; and
narmgemn.
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The nutrient and therapeutic formulas of this invention useful in ameliorating
cancer
can be combined in certain applications for the treatment of cancer in females
with hormone
replacement formulas or drugs and or formulas or drugs for the treatment of
osteoporosis.
Specific osteoporosis formula ingredients include:
Osteo I = vitamin C; quercitin; 22-oxa-vitamin D3; calcium and taurine.
Osteo II = Osteo I components with:
N-acetylcysteine, zinc, estrogenic soy components (isoflavones), soy saponins,
and
magnesium,
Osteo III = Oseto II with:
vitamin B6, and sodium bicarbonate.
Osteo IV = Osteo III with
sodium fluoride, l-lysine, and vitamin K.
Osteo V= Osteo VI with:
strontium, chromium, ipriflavone, and boron.
The listed osteoporosis formulas can be combined with any of the cancer
protective or
therapeutic formulas.
The listed osteoporosis formulas can themselves be employed for protection
from or
amelioration of the symptoms and conditions of osteoporosis. Preferred
osteoporosis
formulas for used in the absence of the cancer formulations herein include the
components
listed in Osteo I-V along with a source of proanthocyanidin or bioflavonoid
(pine bark
extract, bilberry extract, tea polyphenols, etc.) and a source of neovascular
regulatory and/or
promoter of collagen synthesis (e.g., genistein, cartilage, etc.).
Formulas 1-18 (including A and B formulas) are optionally combined with
aspirin or
NSAIDS (non-steroid anti-inflammatories, including but not limited to
acetaminophen,
ibuprofen, with the priviso that recommended dosages of NSAIDS are employed)
and may
optionally be combined with DHEA (dehydroepiandrosterone). Red Wine Extract, a
powerful proanthocyanidin-containing extract can also be employed in the above
formulas in
place of, or in addition to, other proanthocyanidins.
Sulforaphane, an isothiocyante that can be provided in extracts of broccoli
sprouts can
be combined with any of Formulas I - XVIII to provide inhibition of
carcinogenesis.
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Creatine phosphate and eugenol have antioxidant activity and can be employed
in
formulas of this invention to provide additional protection against oxidative
stress and cell
damage.
Phosphatidylcholine, particularly polyunsaturated phosphalidyl choline, can be
added
to any of the formulas herein to provide control of the blood lipid levels.
All of the above specific formulas can be combined with cellular antioxidants
including glutathione peroxidase, superoxide dismutase andlor catalayze. All
of the above
specific formulas can be combined with fruit and/or grain fiber.
All of the above formulas can be combined with taxol, or structurally related
anticancer agents as well as Juniper yew extract with the proviso that these
materials can
exhibit significant toxic effect. Similarly, the formulas of this invention
can be combined
with mistletoe extract again with the proviso that this material can exhibit
toxic effect.
The formulas of this invention can optionally include nutrients, vitamins and
minerals
other than those specifically listed to supplement particular nutritional
deficiencies of given
1 S individuals, for example, chromium, iron, or other mineral may be provided
or its
concentration increased to supplement a given deficiency. Similarly, a
particular vitamin or
amino acid deficiency can be supplemented. Analogously, a given formulation
can be
adapted for sensitivities or allergies of a given individual.
Specific components listed in Table 2 and in the Formulas herein which are
natural
isolates can be replaced or supplemented with extracts and/or powders (seeds,
etc.) derived
from the natural source of the component.
A number of the components of formulas herein can be obtained from natural
sources.
Isolated major active ingredients can be recombined with extract obtained from
the natural
source to provide minor components that may enhance function of the major
ingredient, e.g.,
purified genistein can be combined with soybean extract for enhanced effect.
The formulas of this invention an also be combined with enzymes such as papain
and
bromelaine to aid digestion.
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TABLE 2: Component Functions for Cancer Formulations
FUNCTIONS
1. Function as antioxidant to control
oxidative stress
2. Function as neovascular regulators
controlling angiogenesis
3. Collagen maintenance; collagen
synthesis
4. Regulate blood lipid levels,
regulate lipoprotein (A)
5. Decrease acidity, pH balance,
digestion/absorption
6. Supplement deficiencies
7. Inhibit aberrant methylation
8. Stimulate immune response and/or
differentiation
9. Regulate blood glucose and/or
insulin
10. Regulate homocysteine, inhibit
homocysteine
11. Anti-tumor/Anti-cancer effect
Average Adult
Formula Components Functions Daily Dose
Range
dose/da
Pine Bark Extract (<85% OPC 1, 2, 3 3 - 2,000 m
Bilbe Extract 25% OPC 1, 2, 3 S - 1,500 m
Gra a Seed Extract Extract 95-100%1, 2, 3 5 - 2,000 m
OPC
Gin ko Biloba 24% 1, 2, 3 5 - 1,500 m
Green Tea Pol henol 1, 3, 4, 9 10 - 10,000
m
Sil arin 80% concentrate 1, 2 10 - 1,000
m
Saw Palmetto 1, 4, 11 S - 1,500 m
I Vitamin C ascorbic acid 1, 3, 4, 6, 10 - 5,000
10, 11 m
Vitamin E D-al ha-toco he 1 acetate1, 4, 6 5 - 800 m
Vitamin A 1, 6, 11 1,000 ILJ -
25,000 IU
Antioxidant carotenoids: 1, 4, 6, 10,
11
lutein 1 - 300 mg
zeaxanthin 1 - 300 mg
lycopene 1 - 300 mg
beta carotene, etc. 10 - 100,000
IU
uercitin and other antioxidant 1, 3, 11 1 - 2,000 m
bioflavanoids
Taurine homotaurine 1, 6 5 - 7,000 m
Thioctic acid a-li oic acid 1 5 - 1 000 m
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TABLE 2 (CONTINUED
N-acet 1-L-c steine 1, 4, 6, 7, 5 - 3,000 m
10
L-c steine 1, 6, 7, 10 1 - 2,000 m
Glutathione 1 1 - 1,000 m
Co 10 1,6 4-400m
Chondroitin Sulfate 2, 3 10 - 10,000
m
Glucosamine Sulfate 2, 3 10 - 10,000
m
Soy Isolate (e.g., genistein and 2, 3 50 - 1,500
other plant mg
isoflavones
Protamine Sul hate 2, 3, 9 10 - 900 m
Cartila a bovine 2, 3 1 - 30,000
m
Cartila a shark 2, 3 1 - 1,499 m
Vitamin B5 antothentic 6 1 - 200 m
Vitamin B1 thiamine 6 10 - 100 m
Folic Acid 6, 10 100 -1,500m
Vitamin B2 Riboflavin 6 1 - 50 m
Vitamin B6 P ridoxine HCl 6, 10 1 - 200 m
Vitamin B 12 C anocobalamin 1 % 6, 10 1 - 100 m
Nicotinamide (Vitamin B3, nicotinamide6 1 - 500 mg
ascorbate
B com lext 6, 10 1 - 500 m
Calcium Krebs 4, 6, 11 10 -10,000
m
Zinc Krebs 1, 6, 9 10 - 3,000
m
Ma esium Krebs 6, 9 3 - 10,000
m
Chromium nicotinate 1, 4, 6, 9 2 - 50 m
Selenium 1-selenomethionine) 1, 6, 11 1 - 50 m
Potassium citrate 1, 6 30 - 18,000
m
Strontium 6 1 - 800 m
Co er cu ric sulfate 6, 11 1 - 500 m
Man anese Krebs 3, 6 10 - 100 m
I
Silicon ma nesium trisillicate 6 10 - 200 m
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TABLE 2 CONTINUED
Mineral Com lex l, 4, 6, 9, 1 - 50,000
11 m
Sulfora hane 1, 11 1 me - 20 m
Chloro h 11 1, 11 1 m - 3,000
m
Pectin 1, 11 1 mg -
10,000 m
Ome a-3-fatt acids flax seed owder 4, 6, 11 10 - 30,000
m
Essential fatty acids (dienoic conjugated1, 4, 6, 11 10 - 10,000
linoleic mg
acid
G1 zze n licorice 3, 11 1 me - 20 m
Allicin arlic extract 3, 11 1 me - 50 m
Vitamin D3 6, 8 1 - 10,000
IU
Melatonin 11 1 - 100 m
L-carnitine Acet 1-L-carnitine 1, 4 10 - 3,000
m
Indole-3-carbinol 1 1 - 1,000 m
Ph osterols Cholestatin III 1, 4, 11 10 - 3,000
m
Creatine hos hate 1 10 - 20,000
m
Fenu reek Seed owder 4, 9 10 - 30,000
m
G ema s Ivestre 1, 3, 9 10 - 3,000
m
Vitamin K1 6 15 - 75
Monoterpene (e.g., Limonene, Naringinen11 100 mcg -
200 m
Sesamin/Sesamolin 4 1 me - 40 m
Biotin 6, 8 1 mcg - 5 mg
Dried mushroom extract 11 1 mg -
10,000 m
Phosphatidyl choline (lecithin) 4, 6 100 mg -
50,000 m
L-I sine 6 10 - 13,000
m
L-ar mine 6, 8 10 - 9,000
m
L- lutamine 6 10 - 13 000
m
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TABLE 2 (CONTINUED
L-methionine 6, 7 10 - 300 m
Branched Chain Amino Acids' 3, 6 10 - 70,000
m
Betain HCl 5, 6 1 - 10,000
m
Pe sin 5, 6 1 - 10,000
m
Sodium Bicarbonate S, 6 1 - 10,000
m
~ B complex = Vit. B1, Vit. B2, Vit. B3, Vit. B5, Vit. B6, and Vit. B12.
*Branched Chain Amino Acids = L-leucine, L-isoleucine, and L-valine.
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Components that enhance or facilitate desirable enzyme activity, e.g., lysyl
oxidase
(an enzyme which participates in collagen synthesis); nitric oxide inhibitors,
other antioxidant
carotenoids or flavonoids, additional antihyperlipoproteinemics, including
probucol and
blood thinning agents, e.g., heparin can be combined with any of the formulas
listed above.
Cellular antioxidants, such as the enzymes: superoxide dismutase and catalyze
or
thiols, including glutathione peroxidase, can be included in any of specific
formulas listed
above. L-carnitine (which may be in the form of L-acetyl carnitine or L-
propionyl carnitive)
can be combined with any of the specific formulas above.
Treatment using the compositions of this invention can be combined with
hormone
therapy and or hormone supplementation, including estrogenic hormone therapy
or
supplementation, thyroid hormone therapy or supplementation, treatment or
supplementation
with human growth hormone (HGH) and/or treatment or supplementation with DHEA
(dehydroepiandrosterol).
The formulas of this invention can also be combined with appropriate growth
factors,
1 S growth factor inhibitors and growth factor binding agents including, among
others, fibroblast,
epidermal, interleuken transforming and platelet-derived growth factors,
agents that bind
hyaluronic acid and/or collagen. The formulas of this invention can be used in
combination
with immune suppression of T-lymphocytes.
The formulas of this invention can also be employed in combination with
therapeutic
methods shown to have beneficial effect for the disorders, conditions and
diseases discussed
herein.
Other optional components of the formulas of this invention include
antioxidants
and/or preservatives, such as BHT (Butylated hydroxytoluene), BHA (Butylated
hydroxyanisole), ethoxiquin and diphenyl phenylenediamine.
In general the amount of each component employed in the different compositions
of
this invention is sufficient to provide the desired therapeutic effects) or
nutritive effect(s), as
discussed herein, to an individual and avoid toxicity with continuing regular
dosing. Because
compositions of this invention can have multiple components with similar
functionality, the
effective amount of any given component needed to provide a given level of
function in a
given composition will depend on the quantities of other functionally similar
or otherwise
related components to be included in the composition.
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Table 2 provides a summary of certain biochemical functions of components that
are
useful in cancer-protective and cancer-therapeutic formulas of this invention.
A single
component may provide more than one of the listed biological functions in a
given
composition. Table 2 provides a list of exemplary components of the formulas
of this
invention providing a preferred range of amounts of individual components that
can be
combined in the formulas of this invention. The amounts listed in Table 2 are
average daily
adult dosages. Biological functions associated with osteoporosis are not
listed.
As listed in Table 2, the cancer-preventative and therapeutic formulas of this
invention comprise components that ( 1 ) have antioxidant function to control
oxidative stress
and prevent cell damage, (2) promote and/ or stimulate collagen synthesis to
provide healthy
tissue and inhibit metastasis and recurrence, are (3) neovascular regulators
which control
angiogenesis and function to limit blood supply to cancers, (4) regulate blood
lipid,
particularly lipoprotein (a), levels, (5) decrease cell/tissue acidity and
promote pH balance,
(6) supplement dietary deficiencies, non-absorption, cachexia or nutrient
spillage, (7) inhibit
or prevent aberrant methylation, (8) stimulate or enhance immune response or
cell
differentiation, (9) control blood glucose levels, (10) lower homocysteine
levels or (11) have
other antitumor or anticancer activity.
One or more of the functionalities listed in Table 2 can be provided in the
compositions of this invention by art-known equivalents including equivalents
from natural
sources and/or drug equivalents.
Compositions of this invention can be provided in a variety of nutrient and
dosage
forms including pills, tablets, capsules, lozenges, powders, solutions,
suspensions, injection
dosage forms and the like. Compositions of this invention can be administered
to individuals
orally, intravenously, and by various forms of injection and various forms of
absorption (e.g.,
dermal, sublingual). Active ingredients of the formulas of this invention can
be combined
with excipients, fillers, buffering agents and the like to prepare desired
dosage forms.
Generally preferred dosage forms are those appropriate for oral
administration. In cases of
use for cancer therapy, the optimum mode of administration can depend upon the
type of
cancer.
The formulas of this invention that are useful in the treatment and prevention
of the
various disease conditions discussed above combine a number of related
ingredients. The
therapeutic and preventative compositions of this invention are based at least
in part on the
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inventor's recognition of similarities in etiology of the various cancers. In
particular, the
inventor considers that the development, growth and metastasis of
malignancies, is at least in
part, caused by or exacerbated by oxidative stress and tissue destruction
associated with
oxidative damage. Further, the inventor considers that in each of the disease
conditions and
symptoms, for which formulas are provided herein, that stimulating and or
promoting
collagen synthesis is an important factor in prevention and treatment. in this
regard, the
various disease conditions discussed herein also relate in part aberrant
tissue growth, for
example due to lack of proper growth factors or lack of growth factor
inhibitors.
Furthermore, individuals with cancer also suffer from the effects of
deprivation of adequate
nutrient, vitamin, cofactor and mineral supplies and particularly from
inadequate supplies of
nutrients, cofactors and the building blocks needed for restoration of the
collagen matrix
which is necessary for regeneration and healing of tissue in general.
The treatment methods described herein employing the formulations of this
invention
are believed to derive unique and unexpected benefits from complementary and
synergistic
interactions between the various formula components acting together upon the
various
symptoms and conditions associated with the various diseases and disorders
discussed herein.
The success of these compositions in the treatments described is, at least in
part, attributable
to the multi-factor strategy employed to balance nutrient and metabolic
deficiencies and to
control oxidative stress, while promoting or stimulating cell and tissue
repair or healing
and/or collagen matrix repair, and inhibiting angiogenesis.
The proposed function of components listed in the specific formulas of this
invention
and stated to be options herein are discussed above, are specified in Table 2
or are known to
those of ordinary skill in the art.
A broad effective dose range (daily adult dose) for individual active
components of
the formulas of this invention. The broad dose range given in the table
provides guidance
regarding approximate minimal effective amounts of given components from any
source and
guidance for dosage of equivalents. The maximum dosages listed are estimates
based
generally upon what is known in the art concerning the individual components
listed. The
maxima listed may merely be based on an estimate of maximum amount that can be
practically provided in a daily oral dosage form. Dosages can be readily
adapted by those of
ordinary skill in the art for use of alternate forms or sources of the
components listed or for
use of functional equivalents. Dosages can be readily adapted for desired
dosing schedules
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and to match individual needs or problems of a given patient by those of
ordinary skill in the
art.
U.S. Patent application 08/018,273, filed February 4, 1998, which is
incorporated in
its entirety by reference herein relates to nutrient and therapeutic
formulations for treatment
of cardiovascular disease and the complications of diabetes. The formulas
therein combine
antioxidants, neovascular regulators and other components having particular
benefits for
cardiovascular disease and diabetes complications. This patent application
provides
exemplary formulations including certain of the components herein and provides
additional
guidance for appropriate dosage. Formulas of this invention can be adapted for
treatment of
diabetics having cancer using components and dosages provided in this U.S.
application.
Table 2 provides a summary of the general biological functions of most
components
that are believed to be beneficial for the treatment of cancer. This listing
provides the
inventor's current understanding of the functions provided by components
included in the
preferred composition and provides guidance for the choice of alternative
components with
similar functionality. The inventor, however, does not wish to be bound by the
specific
functional correlations listed in these tables or by proposed functionality of
individual
activity. The etiology of the diseases and conditions discussed herein is
complex and a given
component of a formula of this invention may have several different effects.
In some cases,
the component listed in the table is itself a mixture, for example, pine bark
extract is a
combination of naturally occurring compounds. In these cases, different
components of the
listed mixtures may contribute to different functions listed in Table 2.
The compositions of this invention specifically ameliorate cancer. The
diagnosis and
symptoms of various cancer conditions are understood in the medical arts and a
variety of
methods are known in the art to evaluate the severity and extent of the
conditions.
Exemplary sources of certain components of the formulas herein are as follows:
The following are sources of ingredients listed in Table 2:
Bilberry extract, as a dry hydroalcohol extract containing anthocyanosides
corresponding to 25% (by weight)of anthocyanidines obtained from Indena
(Milan, Italy).
Grape Seed Extract (Leucocyanidins) (90-100% OPCs) can be obtained from Indena
(Milan,
Italy).
Pine Bark Extract (OPC 90%) can be obtained from Euromed (Barcelona, Spain).
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Green tea polyphenols (95%, min. 75% catechins, low caffeine) can be obtained
from
TSI, International, Inc. (New York, NY).
N-Acetyl-1-cysteine (99%), L-carnitive base (Product No. 18-1870-00), CoQlO
(ubidecarenone), 1-(+)-ascorbic acid, riboflavin (USP, FCC, Water CAS 7732-18-
5 max
1.5%), pyridoxine hydrochloride (USP, FCC), and vitamin B12 (USP) were
obtained from
Schweizerhall, Inc. (Piscataway, NJ). Vitamin B12 (cyanocobalamine can be
diluted in
inactive filler to give a 1 % by weight mixture). Acetyl-R-carnitive is
available from several
manufacturers.
Vitamin A acetate (T-500A) cam be obtained from Hoffinann-La Roche (Belvidere,
NJ).
Taurine (98.5% min.) and folic acid (USP) were obtained from Seltzer
Chemicals,
Inc. (Carlsbad, CA). Homotaurine is available from several manufacturers.
Linoleic Acid (High Purity, 99% min) can be obtained from Spectrum Quality
Products (Gardena, CA).
Lipoic Acid (99.8%) and protamine sulphate (USP) were obtained from Maypro
Industries, Inc. (Harrison NY).
Lutein is provided in a nutrient composition "FloraGlo" Lutien (Trademark,
Kemin
Industries, Des Moines, IA) comprising 5% by weight lutein and 0.22%
zeaxanthin. This
material is in beadlet form and also comprises vegetable oil, natural vitamin
E (as a
preservative), rosemary, natural citric acid, gelatin, sucrose and starch. See
U.S. Patent
5,382,714.
Chondroitin sulphate as the sodium salt produced by the Strandberg method from
beef
trachea can be obtained from Weinstein Nutritional Products (Irvine, CA).
Chromium picolinate "Chromax" can be obtained from Nutrition 21 (San Diego,
CA).
Calcium (Krebs)22%, Zinc (Krebs) 30% and Magnesium (Krebs) were obtained from
Monarch Nutritional Laboratories (Ogden, UT}.
Potassium citrate (NF granular) complying with USP, FCC and FAO/WHO Food
additive specifications can be obtained from Archer Daniels Midland.
Shark cartilage powder (100%, 200 mesh) can be obtained from Global Trading
{USA) Inc. (Union, NJ).
Isolated soy protein ("Supro" HD90, Trademark) can be obtained from Protein
Technologies International (St. Louis, MO). Isolate soy protein products from
this source are
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reported to typically contain (in mg/g protein) 0.15 to 0.72 mg daidzein, 0.48
to 1.51 mg
genistein, 0.05 to 0.26 glycitein with a total isoflavone content of 0.68 to
2.49 mg (aglucone
units adjusted for molecular weight).
Phytosterol complex, "Cholestatin III" can be obtained from several sources.
Vitamin E, d-alpha-tocopheryl acetate {natural source, powder) can be obtained
from
B&D Nutritional Ingredients, Inc. (Carlsbad, CA).
Flax seed powder containing about 23 mg of alpha-linolenic acid (omega-3-fatty
acid)
per 100 grams powder can be obtained from Honeyville Grain Inc. (Salt Lake
City, UT).
Fenugreek seed powder can be obtained from Botanicals International (Long
Beach,
CA).
Ginkgo biloba L. powder extract about 26% flavonglycosides and Gymnema
sylvestre
powder can be obtained from Motherland International Inc. (Chino, CA).
Other components listed in Table 2 can be obtained from a variety of
commercial
sources.
Those of ordinary skill in the art of formulation of nutrients and therapeutic
compositions will appreciate that components functionally equivalent to those
specifically
disclosed herein, as well as alternative forms and sources in addition to
those specifically
disclosed herein for individual composition ingredients are available. This
invention is
intended to encompass all such functional equivalents and alternatives that
are readily known
to the art.
41
