Note: Descriptions are shown in the official language in which they were submitted.
CA 02516678 2005-08-18
Supplemental Dietary Composition For Enhancing Muscle Performance
And/or Recovery from Fatigue
Field of the Invention
The present invention relates to a supplemental dietary composition, including
GAKIC, which enhances muscle performance and/or recovery from fatigue. The
present invention also relates to methods of enhancing muscle performance
and/or
recovery from fatigue by consuming a supplemental dietary composition that
includes
GAKIC. The present invention also provides for a method of manufacturing a
supplemental dietary composition, including GAKIC, which enhances muscle
performance and/or recovery from fatigue.
Background of the Invention
Ketoacids and cationic or dibasic amino acids are known to improve athletic
dynamic muscle strength and muscle work, and recovery from acute exhaustive
anaerobic strength training exercise. For example, U.S. Patent No. 6,100,287
("the '287
patent"), which is incorporated herein by reference in its entirety, discloses
a
supplemental dietary composition containing a glycine and L-arginine (in a
monohydrochloride salt form) alpha-ketoisocaproic acid calcium to enhance
muscle
performance and/or recovery from fatigue. The '287 patent discloses
administration of
this composition in Publix~ low calorie cranberry juice.
Summary of the Invention
The present invention provides for a supplemental dietary composition which
enhances muscle performance and/or recovery from fatigue. GAKIC, or glycine
and L-
CA 02516678 2005-08-18
arginine (which is preferably in base form but may also be in salt, e.g.,
monohydrochloride salt, form) alpha-ketoisocaproic acid calcium, has a strong
bitter
taste which may cause aversive reactions in individuals when ingested
directly. The
present invention provides for GAKIC formulations that effectively reduce,
e.g.,
suppress, the bitter taste of GAKIC. As used herein, the term GAKIC may refer
to any
form of glycine and L-arginine (either in base form or in a salt, e.g.,
monohydrochloride
salt, form) alpha-ketoisocaproic acid calcium.
For example, in an embodiment, the present invention provides a supplemental
dietary composition including GAKIC and an effective amount of a flavor
component,
e.g., a bitter-mask flavor, polyvinylpyrrolidone ("PVP"), a sweetener such as
acesulfame
potassium (ACE-K), etc., that effectively reduces, e.g., suppresses, the
bitter taste of
GAKIC. The flavor component may be present in any amount effective to reduce,
e.g.,
suppress, the bitter taste of GAKIC, and thus improve the palatability of
GAKIC. For
instance, the present invention provides a supplemental dietary composition
including
GAKIC and an effective amount of, e.g., bitter-mask flavor, PVP, a sweetener
such as
ACE-K, and/or fruit flavorings.
In an embodiment, the supplemental dietary composition of the present
invention
including GAKIC and an effective amount of a flavor component is in the form
of a
powder, tablet, caplet or drink, e.g., a ready-to-drink beverage in a
polyethylene bottle
or can. The supplemental dietary composition may be any form, e.g., a powdered
beverage mix, a low-calorie powdered beverage mix, etc. Alternatively, the
supplemental dietary composition may be in the form of a coated tablet or
caplet. For
example, the flavor component may be provided in the coating of a coated
tablet or
caplet. In such an embodiment, the coating may include a flavor component and
a
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CA 02516678 2005-08-18
supplemental dietary composition that includes part-hydrolyzed polyvinyl
alcohol,
titanium dioxide, polyethylene glycol (PEG), and/or talc, and may further
include
hydroxypropyl methylcellulose, soy lecithin, and/or polysorbate.
In an embodiment, the present invention may provide a supplemental dietary
composition including GAKIC and an effective amount of a flavor component,
wherein
the flavor component includes a bitter-mask flavor, e.g., PVP. The bitter-mask
flavor
may be present in any amount that effectively reduces, e.g., suppresses, the
bitter taste
of GAKIC. For example, the bitter-mask flavor may be present in an amount
between
about 0.01 % and about 10 % by weight of the supplemental dietary composition.
In an
embodiment, the bitter-mask flavor is present in an amount between about 0.1 %
and
about 5 %, and in another embodiment, is present in an amount that is about
0.2 % by
weight of the supplemental dietary composition.
In an embodiment, the present invention may provide a supplemental dietary
composition including GAKIC and an effective amount of a flavor component,
wherein
the flavor component includes a sweetener such as ACE-K. The ACE-K may be
present in any amount sufficient to reduce, e.g., suppress, the bitter taste
of GAKIC.
For instance, the ACE-K can be in an amount between about 0.01 % and about 10
% by
weight of the supplemental dietary composition. In an embodiment, the ACE-K is
present in an amount between about 0.1 % and about 5 %, and in another
embodiment,
is present in an amount that is about 0.24 % by weight of the supplemental
dietary
composition.
In an embodiment, the present invention provides a supplemental dietary
composition including GAKIC and an effective amount of a flavor component,
wherein
the GAKIC is present in an amount sufficient to enhance muscle performance
and/or
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CA 02516678 2005-08-18
recovery from fatigue. For example, GAKIC may be present in an amount between
about 10 % and about 90 % by weight of the supplemental dietary composition.
In an
embodiment, GAKIC may be present in an amount between about 20 % and about 80
by weight of the supplemental dietary composition. Additionally, the
supplemental
dietary compositions of the present invention may contain between about 31.1 %
and
about 33.6 % of GAKIC by weight of the supplemental dietary composition.
In an embodiment, the present invention provides a supplemental dietary
composition including GAKIC, wherein some or all of the GAKIC in the
supplemental
dietary composition contains fine-milled particles. Advantageously, the fine-
milled
particles may have an average particle size between about 50 nm and about 1
mm, and
in another embodiment, between about 100 nm and about 1 Nm, and in yet another
embodiment, between about 200 nm and about 800 nm. The supplemental dietary
composition may also include an effective amount of a flavor component. In an
embodiment, the fine-milled particles are present in an amount between about
0.001
and about 10 %, and in another embodiment, between about 0.001 % and about 5
%,
and in yet another embodiment, at, e.g., about 0.003 % by weight of the
supplemental
dietary composition.
In an embodiment, the supplemental dietary compositions of the present
invention contain GAKIC in the form of fine-milled particles, and an effective
amount of
a flavor component. Additionally, the supplemental dietary compositions may
contain
GAKIC in the form of granules and fine-milled particles, and an effective
amount of a
flavor component. In an embodiment, the supplemental dietary compositions
contain
GAKIC in the form of granules and fine-milled particles in a core, and an
effective
amount of a flavor component in a coating surrounding the core.
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CA 02516678 2005-08-18
The present invention provides for methods of enhancing muscle performance
and/or recovery from fatigue by consuming the supplemental dietary
compositions of
the present invention. For example, in an embodiment, the present invention
provides
for methods of increasing fatigue resistance index, increasing total work
output, and/or
improving dynamic performance during concentric or eccentric contraction, by
consuming the supplemental dietary compositions of the present invention. As
set forth
above, the use of GAKIC in the manner described herein may provide various
effects or
benefits. For example, the supplemental dietary composition may perform,
provide or
enable one or more of the following: reduction of muscle fatigue toxin;
getting more
explosive reps and performance in minutes; a substantially immediate 10.5%
increase
in strength; a substantially immediate increase in muscle power; more
explosive reps
and performance substantially immediately; sustaining of greater muscle force
(concentric torque); sustaining of greater muscle torque; an increase in
fatigue
resistance; enhancement of muscle work output; improvement of performance
compared to carbohydrate placebo; an increase in ability to sustain muscle
work by up
to about 12%; improvement in resistance to fatigue by an average of 28% at the
beginning of exercise; providing an ideal environment for intense muscle
anaerobic
exercise; an increase in overall performance by delaying muscle fatigue;
demonstrable
results in greater concentric muscle work; improvement of dynamic muscle
function
under intense exhaustive anaerobic conditions; an increase in ability to
sustain muscle
force, total muscle work and delay fatigue; provide gains in muscle strength
and size
over time (due to the overload principle); force muscles to contract at max or
near max
tension of a given period of time; and attenuation of a drop in mean power
output. The
methods of enhancing muscle performance and/or recovery from fatigue by
consuming
CA 02516678 2005-08-18
the supplemental dietary compositions of the present invention may be used on
a
human or other animals.
The present invention also provides for a method of manufacturing a
supplemental dietary composition which enhances muscle performance and/or
recovery
from fatigue. For example, in an embodiment, the present invention provides
for a
method of manufacturing a supplemental dietary composition by combining GAKIC
and
an effective amount of a flavor component that reduces, e.g., suppresses, the
bitter
taste of GAKIC. The method of manufacturing the supplemental dietary
composition
may include preparing a mixture of GAKIC, forming a core from the mixture, and
coating
the core with a coating that contains an effective amount of a flavor
component to form
the supplemental dietary composition.
In an embodiment, the method of manufacturing the supplemental dietary
composition includes preparing a mixture of GAKIC, fine-milling the mixture,
and
combining an effective amount of a flavor component with the mixture to form
the
supplemental dietary composition. For instance, the method of manufacturing
the
supplemental dietary composition may include preparing a mixture of GAKIC,
fine-
milling the mixture, forming a core from the mixture, and coating the core
with a coating
that contains an effective amount of a flavor component to form the
supplemental
dietary composition.
In another embodiment, the method of manufacturing the supplemental dietary
composition includes preparing a first mixture of GAKIC, granulating the first
mixture to
obtain granules, fine-milling a second mixture of GAKIC to produce fine-milled
particles,
combining the granules with the fine-milled particles to form a third mixture,
and
combining an effective amount of a flavor component with the third mixture to
form the
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CA 02516678 2005-08-18
supplemental dietary composition. The method of manufacturing the supplemental
dietary composition may also include, e.g., preparing a first mixture of
GAKIC,
granulating the first mixture to obtain granules, fine-milling a second
mixture of GAKIC
to produce fine-milled particles, combining the granules with the fine-milled
particles to
form a core, and coating the core with a coating that contains an effective
amount of a
flavor component to form the supplemental dietary composition.
Detailed Description of the Invention
The term "an effective amount", as used herein with respect to the flavor
component, refers to an amount sufficient to reduce, e.g., suppress, the
bitter taste of
GAKIC or otherwise improve the palatability of the GAKIC. As set forth above,
the term
GAKIC, as used herein, may refer to any form of glycine and L-arginine (either
in base
form or in a salt, e.g., monohydrochloride salt, form) alpha-ketoisocaproic
acid calcium.
Preferably, the present invention provides for GAKIC which includes L-arginine
in base
form. Use of the free base may offer the advantage that molar formulations
utilizing L-
arginine free base require only about 82.69% of the gram amount required for
utilizing
L-arginine HCL, thereby enabling the use of a smaller serving size to achieve
a
comparable benefit, as compared to GAKIC that includes L-arginine in a salt,
e.g.,
monohydrochloride salt, form.
The present invention, according to an embodiment, provides for a supplemental
dietary composition including GAKIC which, e.g., enhances muscle performance
and/or
recovery from fatigue and reduces, e.g., suppresses, the bitter taste of
GAKIC. For
example, in an embodiment, the present invention provides a supplemental
dietary
composition including GAKIC and an effective amount of a flavor component such
as,
e.g., bitter-mask flavor, PVP, a sweetener such as acesulfame potassium (ACE-
K), etc.
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CA 02516678 2005-08-18
In an embodiment, which is set forth in additional detail in Example 1, the
present
invention provides for a supplemental dietary composition including GAKIC,
microcrystalline cellulose, hydroxypropyl cellulose, Opadry II gray, Opadry fx
silver,
corscarmellose sodium, stearic acid, magnesium stearate, silica, and/or ACE-K.
This
embodiment of the present invention may provide for a supplemental dietary
composition which enhances muscle performance and/or recovery from fatigue and
reduces, e.g., suppresses, the bitter taste of GAKIC.
In another embodiment, set forth in additional detail in Example 2, the
present
invention provides for a supplemental dietary composition including GAKIC,
maltodextrin, citric acid, sodium citrate, sodium gluconate, prosweet flavor,
calcium
silicate, fruit punch flavor, dextrose, red flecks, acesulfame potassium,
bitter mask
flavor, PVP, orange flavor, sucralose and FD&C Red #40. This embodiment may
also
provide for a supplemental dietary composition which enhances muscle
performance
and/or recovery from fatigue and reduces, e.g., suppresses, the bitter taste
of GAKIC.
In another embodiment, set forth in additional detail in Example 3, the
present
invention provides for a supplemental dietary composition including GAKIC,
dextrose,
maltodextrin, citric acid, sodium citrate, sodium gluconate, fruit punch
flavor, ACE-K,
bitter-mask flavor, PVP, orange flavor, sucralose, and/or FD & C Red #40. This
embodiment may also provide for a supplemental dietary composition which
enhances
muscle performance and/or recovery from fatigue and reduces, e.g., suppresses,
the
bitter taste of GAKIC.
A discussion of some of these ingredients is set forth below:
GAKI C
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GAKIC (glycine and L-arginine - in a base form or in a monohydrochloride salt -
-
of alpha-ketoisocaproic acid calcium), is a combination of ketoacids and amino
acids
that enhance muscle performance and/or recovery from fatigue.
In a preferred embodiment, illustrated in further detail by Examples 1 through
3,
GAKIC contains L-arginine (45 %), alpha-ketoisocaproic acid calcium salt (29
%), and
L-glycine (18 %).
GAKIC may be present in the supplemental dietary composition in any amount
sufficient to enhance muscle performance and/or recovery from fatigue. For
example,
GAKIC may be present in an amount between about 10 % and about 90 % by weight
of
the supplemental dietary composition. Preferably, the supplemental dietary
compositions of the present invention contain GAKIC in an amount between about
20
and about 80 % by weight of the supplemental dietary composition. More
preferably,
GAKIC is present in an amount of, e.g., about 33.645% by weight of the
supplemental
dietary composition.
According to an embodiment of the present invention, the supplemental dietary
composition may include between about 10 g and 12 g of GAKIC per serving. For
instance, in an embodiment, the supplemental dietary composition may include
about
10.2 g of GAKIC per serving, the GAKIC including L-arginine in a base form.
Alternatively, in an embodiment, the supplemental dietary composition may
include
about 11.8 g of GAKIC per serving, the GAKIC including L-arginine in a
monohydrochloride salt form. The use of L-arginine in base form enables a
smaller
serving size to be used.
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Flavor Component
As used herein, a "flavor component" refers to any ingredient, e.g., excipient
or
combination of excipients, that may reduce, e.g., suppress, the bitter taste
of GAKIC,
either alone or in combination with other flavor components or excipients.
Examples of flavor components may include, but are not limited to, bitter-mask
flavor, PVP, sweeteners such as ACE-K, fruit flavors e.g., fruit punch flavor
and/or
orange flavor, microcrystalline cellulose, hydroxypropyl cellulose, sugars
such as
dextrose, sucrose, fructose, and/or sucralose, maltodextrin, citric acid,
sodium citrate,
and/or sodium gluconate.
The flavor component may be present in any amount effective to reduce, e.g.,
suppress, the bitter taste of GAKIC. For example, the flavor component may be
present
in an amount between about 10 % and about 90 % by weight of the supplemental
dietary composition. Preferably, the flavor component is present in an amount
between
about 10 % and about 80 %, and more preferably between about 20 % and about 70
by weight of the supplemental dietary composition.
According to an embodiment of the present invention, the supplemental dietary
composition may include about 23 g of flavor component per serving.
Alternatively, the
supplemental dietary composition may include about 3 g of flavor component per
serving.
Bitter-Mask Flavor
As used herein, "bitter-mask flavor" refers to a proprietary group of
ingredients
that is specifically formulated and used to mask the bitter taste of GAKIC.
The bitter-
mask flavor may be present in any amount effective to reduce, e.g., suppress,
the taste
of GAKIC. For example, the supplemental dietary composition of the present
invention
CA 02516678 2005-08-18
may contain bitter-mask flavor, e.g., PVP, in an amount of about 0.0675 grams
per
serving.
ACE-K
ACE-K, or acesulfame potassium, may also be used to mask the taste of GAKIC.
ACE-K is a high-intensity, non-caloric sweetener and is approximately 200
times
sweeter than sucrose. ACE-K is not metabolized by the body and is excreted
unchanged. ACE-K is sold under the brand name SunettT"" by Nutrinova, Inc.
Compositions of the present invention may contain ACE-K in any amount
sufficient to reduce, e.g., suppress, the taste of GAKIC. According to an
embodiment of
the present invention, the supplemental dietary composition may include about
0.08 g of
ACE-K per serving. Alternatively, the supplemental dietary composition of the
present
invention may include about 0.00004 g of ACE-K per serving.
The dosage form of the supplemental dietary composition of the present
invention may be provided as a powder beverage mix, tablet, caplet or drink,
e.g.,
ready-to-drink beverage, etc. The supplemental dietary composition may
alternatively
be provided as a capsule, a liquid ready-to-drink beverage, as a ready-to-eat
bar
product, or in any other forms commonly used in the art.
In a preferred embodiment, the supplemental dietary composition of the present
invention is in the form of a coated tablet or caplet. The coating prevents
the bitter taste
of GAKIC, which is preferably in the core, from contacting the palette during
oral
administration, and also enables the tablet or caplet to be swallowed more
easily as
compared to a tablet or caplet that is not coated. This ease of swallowing may
be
especially advantageous, particularly for compositions containing GAKIC, since
the
preferred serving size is approximately 8 tablets or caplets. Preferably, the
flavor
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CA 02516678 2005-08-18
component is in the coating. More preferably, the coating contains ACE-K,
Opadry II
gray, and/or Opadry fx silver. Other excipients commonly used in the art may
also be
added in the coating.
The supplemental dietary compositions of the present invention may be provided
in accordance with customary processing techniques for dietary supplements
wherein
the ingredients are suitably processed and compressed into a tablet or caplet
with
suitable excipients. For instance, the supplemental dietary compositions of
the present
invention may be processed and compressed into tablets or caplets with
microcrystalline cellulose, hydroxypropyl cellulose, croscarmellose sodium,
stearic acid,
magnesium stearate, and/or silica.
The supplemental dietary compositions of the present invention may also be
provided in accordance with customary processing techniques for dietary
supplements
wherein the ingredients are suitably processed into the form of a powdered
beverage
mix. For instance, the supplemental dietary compositions of the present
invention may
be processed with dextrose, maltodextrin, citric acid, sodium citrate, sodium
gluconate,
sucralose, flavoring agents, and/or food coloring. Those of skill in the art
will appreciate
that compositions of the present invention may contain a variety of
excipients.
The supplemental dietary compositions of the present invention may also
contain
ingredients in the form of fine-milled particles. Formulations containing fine-
milled
particles may improve absorption of the supplemental dietary composition by
the body.
In a preferred embodiment, the supplemental dietary composition contains fine-
milled
particles having an average particle size between about 50 nm and about 1 mm,
more
preferably between about 100 nm and about 1 Nm, and even more preferably
between
about 200 nm and about 800 nm.
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CA 02516678 2005-08-18
As used herein, the term "fine-milled" or "fine-milling" refers to the process
of
micronization. Micronization is a mechanical process that involves the
application of
force to a particle, thereby resulting in the break-up of the particle. Such
force may be
applied by collision of particles at high speeds. Micronization may be carried
out, for
example, by grinding or by an air-jet micronizer. In a preferred embodiment,
fine-milled
particles are obtained by jet-milling with nitrogen and compressed air.
As used herein, the term "particle size" refers to particle diameter. The term
"average particle size" means that at least 50 % of the particles in a sample
will have
the specified particle size. Preferably, at least 80 % of the particles in a
sample will
have the specified particle size, and more preferably, at least 90 % of the
particles in a
sample will have the specified particle size.
The size of a particle can be determined by any of the methods commonly known
in the art. The following methods, for example, may be used: sieves,
sedimentation,
electrozone sensing (coulter counter), microscopy, or Low Angle Laser Light
Scattering
(LALLS). The preferred methods for the present invention are the methods most
commonly used in the pharmaceutical industry, such as laser diffraction, e.g.,
light
scattering Coulter Delsa 440SX.
In an embodiment, e.g., caplet form, of the present invention, the
supplemental
dietary composition may contain fine-milled particles in an amount of about
0.0011
grams per serving, while in another embodiment, e.g., powder form, of the
present
invention, the supplemental dietary composition may contain fine-milled
particles in an
amount of about 0.0010 grams per serving.
In an embodiment, the supplemental dietary compositions of the present
invention contain GAKIC entirely in the form of fine-milled particles, and an
effective
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CA 02516678 2005-08-18
amount of a flavor component. In an alternative embodiment of the present
invention,
the supplemental dietary composition may contain GAKIC in the form of both
granules
and fine-milled particles, and an effective amount of a flavor component. For
example,
the supplemental dietary compositions of the present invention may contain
GAKIC in
the form of granules and fine-milled particles in a core, and an effective
amount of a
flavor component in a coating surrounding the core.
As used herein, the term "granule" refers to particles screened from a mesh
size
of 20 to 80. The term "granulate" refers to processes where granules are
produced.
Granulation may be carried out by any methods known in the art.
The present invention provides for methods of enhancing muscle performance
and/or recovery from fatigue by consuming a supplemental dietary composition
containing GAKIC and an effective amount of a flavor component. For example,
the
present invention provides methods of increasing fatigue resistance index,
increasing
total work output, and/or improving dynamic performance during concentric or
eccentric
contraction, by consuming the supplemental dietary compositions of the present
invention. As set forth above, the use of GAKIC in the manner described herein
may
provide various effects or benefits. For example, the supplemental dietary
composition
may perform, provide or enable one or more of the following: reduction of
muscle
fatigue toxin; getting more explosive reps and performance in minutes; a
substantially
immediate 10.5% increase in strength; a substantially immediate increase in
muscle
power; more explosive reps and performance substantially immediately;
sustaining of
greater muscle force (concentric torque); sustaining of greater muscle torque;
an
increase in fatigue resistance; enhancement of muscle work output; improvement
of
performance compared to carbohydrate placebo; an increase in ability to
sustain muscle
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CA 02516678 2005-08-18
work by up to about 12%; improvement in resistance to fatigue by an average of
28% at
the beginning of exercise; providing an ideal environment for intense muscle
anaerobic
exercise; an increase in overall performance by delaying muscle fatigue;
demonstrable
results in greater concentric muscle work; improvement of dynamic muscle
function
under intense exhaustive anaerobic conditions; an increase in ability to
sustain muscle
force, total muscle work and delay fatigue; provide gains in muscle strength
and size
over time (due to the overload principle); force muscles to contract at max or
near max
tension of a given period of time; and attenuation of a drop in mean power
output. The
methods of enhancing muscle performance and/or recovery from fatigue by
consuming
the supplemental dietary compositions of the present invention may be used on
a
human or other animals.
In an embodiment, e.g., a powder, the present invention provides for methods
of
enhancing muscle performance and/or recovery from fatigue by consuming a
supplemental dietary composition containing GAKIC, dextrose, maltodextrin,
citric acid,
sodium citrate, sodium gluconate, fruit punch flavor, ACE-K, bitter-mask
flavor, orange
flavor, sucralose, and/or FD & C Red #40.
In another embodiment, e.g., a powder, the present invention provides for
methods of enhancing muscle performance and/or recovery from fatigue by
consuming
a supplemental dietary composition containing GAKIC, maltodextrin, citric
acid, sodium
citrate, sodium gluconate, prosweet flavor, calcium silicate, fruit punch
flavor, dextrose,
red flecks, acesulfame potassium, bitter mask flavor, orange flavor, sucralose
and
FD&C Red #40.
In another embodiment, e.g., a caplet, the present invention provides for
methods of enhancing muscle performance and/or recovery from fatigue by
consuming
CA 02516678 2005-08-18
a supplemental dietary composition containing GAKIC, microcrystalline
cellulose,
hydroxypropyl cellulose, Opadry II gray, Opadry fx silver, corscarmellose
sodium,
stearic acid, magnesium stearate, silica, and/or ACE-K.
Compositions of the present invention are optionally administered to any
animal
for of enhancing muscle performance and/or recovery from fatigue. The animal
is
preferably a human, a horse, a dog or a pig. The human may be an athlete or a
non-
athlete.
In a preferred method of enhancing muscle performance and/or recovery from
fatigue, the supplemental dietary composition of the present invention is
administered
once daily, and more preferably is administered approximately 45 minutes
before a high
intensity workout. The supplemental dietary composition of the present
invention is
optionally administered at meals. In an embodiment, a serving is 8 tablets or
caplets.
The present invention also provides for a method of making a supplemental
dietary composition useful for enhancing muscle performance and/or recovery
from
fatigue without the bitter taste associated with GAKIC. For example, in an
embodiment,
the method of manufacturing the supplemental dietary composition includes
combining
GAKIC with an effective amount of a flavor component to form the supplemental
dietary
composition. The method of manufacturing the supplemental dietary composition
may
also include preparing a mixture of GAKIC, forming a core from the mixture,
and coating
the core with a coating that contains an effective amount of a flavor
component to form
the supplemental dietary composition.
In an embodiment, the method of manufacturing the supplemental dietary
composition includes preparing a mixture of GAKIC, fine-milling the mixture,
and
combining an effective amount of a flavor component with the mixture to form
the
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CA 02516678 2005-08-18
supplemental dietary composition. For instance, in an embodiment, the method
of
manufacturing the supplemental dietary composition includes preparing a
mixture of
GAKIC, fine-milling the mixture, forming a core from the mixture, and coating
the core
with a coating that contains an effective amount of a flavor component to form
the
supplemental dietary composition.
In another embodiment, the method of manufacturing the supplemental dietary
composition includes preparing a first mixture of GAKIC, granulating the first
mixture to
obtain granules, fine-milling a second mixture of GAKIC to produce fine-milled
particles,
combining the granules with the fine-milled particles to form a third mixture,
and
combining an effective amount of a flavor component with the third mixture to
form the
supplemental dietary composition. The method of manufacturing the supplemental
dietary composition may also include preparing a first mixture of GAKIC,
granulating the
first mixture to obtain granules, fine-milling a second mixture of GAKIC to
produce fine-
milled particles, combining the granules with the fine-milled particles to
form a core, and
coating the core with a coating that contains an effective amount of a flavor
component
to form the supplemental dietary composition.
In a preferred embodiment, illustrated in further detail by Example 4, the
method
of manufacturing the supplemental dietary composition includes premixing L-
glycine, L-
arginine, and alpha-ketoisocaproic acid calcium monohydrochloride salt to form
a
GAKIC premix, grinding the GAKIC premix, mixing 7 % polyvinylpyrrolidone (PVP)
with
the GAKIC premix to form a GAKIC-PVP mixture, granulating the GAKIC-PVP
mixture
to obtain granules, screening the granules at a mesh size of 20 to 80,
combining the
granules with fine-milled GAKIC particles, and adding an effective amount of
bitter-mask
flavor and/or a sweetener such as ACE-K to form the supplemental dietary
composition.
17
CA 02516678 2005-08-18
Preferably, the granules and fine-milled GAKIC particles are formed into a
core, and the
core is coated with a coating that contains an effective amount of a bitter-
mask flavor
and/or a sweetener such as ACE-K to form the supplemental dietary composition.
Preferably, the method further includes the step of checking for
uniformity/homogeneity
and then aliquoting into a serving for formulation.
Although the following examples illustrate the practice of the present
invention in
some of its embodiments, the examples should not be construed as limiting the
scope
of the invention. Other embodiments will be apparent to one skilled in the art
from
consideration of the specification and examples.
18
CA 02516678 2005-08-18
Example 1
A serving of a GAKIC composition comprises the following ingredients in caplet
form.
~~-~~:Dieta In redient.-Name==~~,Actives ~ t~ et -~ A~tN~I °_
~ormtitat~
~~ ~Y . 9 ~ f ~ a~',. °.
.,a , _ ~, '-.c,A ,,. ~ r;~x..., .. an,~"'~;.~- :: r~ h.~K~h.;"'~,,~,
'~ro..,~'r ".~."~.'r .;.
,~,,~~~v~ ~1~ sesf~n~~~ ,~~i~n ~ ~ ~.~~~~
.v;' ~ r ~ _~~ ~"'*k y, ~' =': d
f~t'"'..:~p.° .,'s.~ ;....r.- ,.,n:x.:a~'~ ' ..-~'r'v;~.'k'r .,.~'~' ,
GAKIC (glycine-I-arginine-alpha-
ketoisocaproic acid calcium),
ranulated, 89%' 10.1800 99.9902%
2;:u:, ~y~.~~~~ ;~,~,
L-ar inine 43.5000 ;:; -- ~'~,34.9756
Alpha-ketoisocaproic acid
.:5, ," ff,' ~;
calcium salt 28.0000 ~ ~:~x3.2027
L- lycine 17.5000 .' y~2.0017
M~~~YIYI,:Sk'e'?_?"
GAKIC (glycine-I-arginine-alpha-
ketoisocaproic acid calcium),
nanomilled, 89%Z 0.0010 0.0098%
;,.i~,.,.~::f";.rf. iYit,:~,i
L-ar inine 43.5000 ~~ ' '" '0.000489
Alpha-ketoisocaproic acid
calcium salt 28.0000 f ~~a0.000315
L- I cine 17.5000 , ,~.': %0.000197
i f~~ F~ .&' ~ ~ , ~~ ..~° fna x
'_; _r~ , ;.;Other In retiients~~ ~~~~ ~k , ~~-~~~ ~~ ~ . ~>rt ~ _ ~ x~ #". r~
~. . ''
Microc stalline cellulose ~~~~~ r ~' 1.5270 - ~~q~~~' ~ ~ ~f
z ..~.; ,sf~~: .. .
q
H dro ro I cellulose k~~~ 0.8800
~'w, ~. n
r,..;2,~ y~ ~;;=w ~.:: ~. ~_,u ..;, ~'. ;. ., _ ~:~ ~..".;~ .: -~ ,':a,.
Opadry II gray (polyvinyl alcohol ~~~~~~
part. hydrolyzed, polyethylene ' "~~~='-°~'~ , r:
:,..~ ,;,
r f- ~ ;qF ~ . ,.
glycol, titanium dioxide, talc, ..'~:v
FD&C -red #40, FD&C yellow #6, ,~~;~::. ,~~.y,, ~~, '.~.
FD&C blue #2 ~~~~~~~,~~~~~ 0.3840 r "_~, y:f~" "
r : a,
,~.:r...,f; y:"~~'~;-, ~.~~-,.f:;
O ad fx silver of vin 1 ri':~;;~»:~ ry y:,.,,:~.. ~~.,:,A~rf
P rY ( P Y Y ~-; ~ x ;~<~~~=-~-:f~ ~ .~ ~ f
'r f~,y'~a'~ % ~ ' ~ :: -a ~-' c;q,'-.-:
~,_ " m ' ~ , .,~ ~ ~i ...
alcohol-part. hydrolyzed, talc, y ~ ~ ,~ f . =, ,
=.,'.~~<..: ~ : wj~~ s a-
rrre/~rf N. ~rrx' ' .'t:
~~~,'."-r~:v;: .;s~-f:,"i, =d~i~~._,:.r,- -ae:r..
;l~Yqfpl,'n";#': :ld't..~r.J :Sd'. ~ .,';~i,i~ , r'..i"s"m::~-~.'jf,~f 7_- 1
hydroxypropyl cellulose, ~'~~~.-~,~~,~~=HjH,~:: ~~~:~: : ~ :- :~~-'_.
..~~~r.~o,~ ~ ::~..,
~~ ~ ~~ = f ~ j ~~ ~~~ ~~
polyethylene glycol, soy lecithin ~~f~
titanium dioxide, of sorbate 80) ~~~~'~~, 0.2560 ~ x~, _., ~, ~'~ "..~s~
,.S~fp~ ~ ' , ~ /
Croscarmellose sodium3 ~~ ~~~~~~0.1760 ~f~ ~~~ %° ~ '~' /~~
, a,w_ "u.: ,~' r ~?r r r~'~~,~..~~' ~ ~E
:,", SJ'xETD' ~iw '~ ~ / ~~ :r i~3 ,Wy° ~ ~:9 '~T"~ ~_,
-,xgly.4' v'9.,~r;. , ~:f,:~ ,.",:3e ...
_" ,~F.,.~~,_,93r:f- ;.yf; :;;: ~'~~ ~ -'.,.. "mss."~":m~.~. ..,
Stearic acid 0.17 s. .
m.-:~":~s,u,~_~:::::::~:;: 60 ~N~~x.,:=~~~~~N~y:,.~..,s,,, :z:~~N:;~~.:,
,,HS;~;;~.
w ! ~ r~~r~ 0.088 'x~'f~~~ ~'~
Ma nesium stearate a,
Silica4 °~~~~~a 0.0440 x~~' y ~~ ~'~~fi,~~ k~~
f~.slr f',~u, ~..i'6~ , a ~ ~r'~.~
Acesulfame otassium ,~ , .~~_~0.0004 ~'~,:~,f~~ y
s. qs-a~4 r ~ ,.
:°,5314vFw
_ _ ' ',' '~ , . ~ x',7'124-. . ~' , , . ;" , : .; :-.:- ,
19
CA 02516678 2005-08-18
One serving, which consists of 8 caplets, of the supplement of Example 1 is
consumed once a day, preferably on workout days and 45 minutes before a high
intensity workout.
The supplement of Example 1 may also include the following excipients added,
e.g., during the manufacturing process:
Ingredient Details
Primary Ingredient Secondary Ingredient% in Amount
Primary in
IngredientFormula
Polyvinylpyrrolidone
'GAKIC, ranulated, PVP 4 0.4573
89%
Polyvinylpyrrolidone
ZGAKIC, nanomilled (PVP 4 0.000044
89%
3Croscaramelose sodiumSodium chloride < 0.05 0.000088
3Croscaramelose sodiumSodium I colate
< 0.05 0.000088
4Silica Sodium sul hate
< 4 0.00176
CA 02516678 2005-08-18
Example 2
A serving of a GAKIC composition comprises the following ingredients in
powdered beverage mix form.
Dietary ActivesDietary Activesl=.. Formula
Ingredient Ingredientserving I;
Name Rer serving(9)a'
(91
GAKIC
(glycine-I-arginine-alpha- 10.1800 99.990%
ketoisocaproic
acid
calcium),
ranulated
I-ar 48.85% 4.9724
inine
calcium 31.48% 3.2042
keto
isoca
roic
acid
I- 19.68% 2.0034
I
cine
GAKIC
(glycine-I-arginine-alpha- 0.0010 0.010%
ketoisocaproic
acid
calcium),
nanomilled
I-ar 48.85% 0.0005
inine
calcium 31.48% 0.0003
keto
isoca
roic
acid
I- 19.68% 0.0002
1
cine
Wei 10.1810 ' 100.000%
ht' ':
Other Iservin
In
redients
Maltodextrin 18.3100
DE
Citric 2.1760
acid,
fine
gran
Sodium 0.5000
citrate
Sodium 0.5000
luconate
Prosweet 0.3400
flavor,
nat
Calcium 0.2040
silicate
Fruit 0.1687
Punch
flavor,
N&A
Dextrose 0.1000
99
DE
S 0.0850
ectra
flecks,
red
Acesulfame 0.0800
otassium
Bitter 0.0675
mask
flavor,
nat
Oran 0.0169
a
flavor,
nat
Sucralose 0.0100
FD&C 0.0025
Red
#40
Wei ht 22.5606
Totalwei ht 32.7416
One 33 g serving of the supplemental dietary composition of Example 2 may be
consumed once a day, preferably on workout days and 45 minutes before a high
intensity workout.
21
CA 02516678 2005-08-18
The supplement of Example 2 may also include the following excipients added,
e.g., during the manufacturing process:
,-
',
;' 'In'ceitEe i
t Secort~ar ,in red'ent... s:
redient Qt ,gin Puma ~=Ira,i~ Forinu
a~ ~ . - Q
_~.... . _ I. . -.
..~~ra~,. . ~
.n
~
'Prosweet flavor,dextrose 90 - 99%
nat
natural flavor 1 - 10%
ZFruit Punch maltodextrin
flavor, N&A
modified food
starch
corn s ru solids
N&A flavor
3Red spectra um arabic 99.6 - 99.7%
flecks
FD&C Red #40 0.3 - 0.4%
4Bitter mask maltodextrin 96% 0.0648
flavor, nat
natural flavors 3% 0.0020
um acacia 1 % 0.0007
50range flavor, maltodextrin 47% 0.0169
nat
silicon dioxide 35% 0.0059
citric acid 14% 0.0024
natural flavors 4% 0.0007
* 10.18 g of granulated GAKIC is supplied by 11.4382 g of 89% granulated GAKIC
with 4% polyvinylpyrrolidone
(PVP, Providone K-30)
** 0.001 g of nanomilled GAKIC is supplied by 0.0011 g of 89% nanomilled GAKIC
with 4% polyvinylpyrrolidone
(PVP, Providone K-30)
22
CA 02516678 2005-08-18
Example 3
A serving of a GAKIC composition comprises the following ingredients in
powdered beverage mix form.
k,-~s ~. f Fe~~45".,~xH3 '; ' C s , ra~~a
:S'-
-,.' ~ e'
j
w ... Dieta . . ~ . . ,pctdr
Dieta : ~n- redie'rit Nape _ Act es.-: -, t~0~'-
,: 9 ' !~~~'~ , ~ *:
~'f :~ ., n .~ s ~~ >a , r , m , ~.. .
z~.,.-: - ~- -, ~,:> ~V 1 ~-=alt -- ,~g
. .. ~. . ~ : /a ~, ~tl eCt e"~:,; ~ , c
c~ , H . .~ .a - :~ " ~~'. ~:s~ ~ . . ,q eF.~ ., _ ,:., .~ , r ~ r .-
..
. >.., . . d ~ x a.~ : *~ t.~ ~ s le~ ~:*-, .~.
,r ~r,x,.r "~ ~~~ -:z r~'r~ ~:-r -<'s'.~,.?:...,~sa,~.:~..>.'.. ~, s,
a,,iE~... ,..,Yo--N=r
~. s .. ~.,. ..~~ r ~
z'°',~~ ~, ~' .~'~ R.~ s~ ' , ",k.r..~ a ? ~, ~ :,~. ,aye;,-p
~. s .,..~..~
,."~ aF :.~ ~ ,~ a= "t '. -~?"'~'~ y ~-; .l ~L %,:.f.'~ -w ",fix. , ,;~ '~ "
x,.
y
GAKIC (glycine-I-arginine-alpha- 4 ~~;~ ~~
s~.,~~t~wy~%~
ketoisocaproic acid calcium), ~~, , , ,,
1 ranulated 93%' ~v~~H=~- 10.9357 :. ~ 32.164%
I-ar inine 45.47/ %~::~fr~:ev~~;~~~~~~ 4.9725 ."
g -~.:.,~............~;;._..,. .~.*... :.... ,
o N~~~...y;~wl , ~.
calcium keto isoca roic acid 29.30/ ~,:~:~~~a:::.~~~~ " 3.2042 r
r::
~~W~~~"~.uu~.", - x
I- I cine 18. 32 % _~~ ~ ~ , ~ =%2. 0034 . ' ,
GAKIC I cine-I-ar inine-al ha-
(9 Y 9 P ~ ._ -~~c-a :;_
~:r
ketoisocaproic acid calcium),
--~,:::. .~, ,tl ,_,~r y ~;~r, ~ O
2 nanomilled ~~ ~,fr;,~~,_~,;;"f;" 0.0010 ,~ ~,,,~,. _,_: fa 0.003 /0
I-ar inine 48 9 % ~ ~k~~~ ~~~"~ Y 0.0005
calcium keto isoca roic acid 31.5% ~~'~~~~'~~.~~r,~, ; w 0.0003
~. :a. ; ; a . .
1- I cine 19.7% ;;; , - ~~~ 0.0002
-3~'~~'t S ~., dry' ."~Y~' ,% t ~ Y'~' /~' G ~~i ~a ,
3-~~ ". , "' r~s .,z~ d' :
, ~,:.~%~ .,.:~'"'.~j ,$< '', y: y,. ~> ,.r.. .
"~~._: ~.W'e~ '~ ~v ~t.:'~ , :10:936,.
~.. ~ -- ~ - w:
,~;: ~~ ~~ ,
....~f~ ~r.~ ~".~ ~.n~-. pt~Or;ln reclients =, ~# ~ " .~ tsei~rln ~. ~:'
,a .: . . .~' -
3 Dextrose 99 DE 3~~'.~~~._,~!;, 15.0000 ~'y 44.118%
"~~~~ sl~s~°
4 Maltodextrin 10 DE n,::.,~:.-...~=,;;:,~.: 4.5417 13.358 /°
Citric acid, fine ran ~"~~ ~~::~:;2.1760 ~ 6.400%
6 Sodium citrate ~~=~= ";%x=y ~_= 0.5000 ~-~ 1.471
:.-.,a:~.:,.::...,.;~:..df:,.="s:;. : ~r:z~'
t~Z:>%,~ %f%~i% O
7 Sodium luconate ~;u;;~~"*;*;y;;.: 0.5000 ~~;' , 1.471 /o
0.1687 :~ 0.496 /o
8 Fruit Punch flavor, N&A ,_~~r~~~ ,.~ " . °
..... . ..... . ..
::::x?T,~:;y=~zu;;;a°~;. =.~;s=~-r;a~'y n .~.
9 Acesulfame otassium ~~~x=:::;~*::~~.:r;~5~ °
..-,~:*y~,:::,::..:;~:.",.:*:: 0.0800 , 0.235 /o
s ~~"_~:=~s~~-y
~..~~,...r .;...,:- o
Bitter mask flavor, nat ==~r~,~ k%-.m°,~ 0.0675 ... 0.199 /o
-...-.. .._. ~r,:.=~-~ ~ ...:-_ ..
11 Oran a flavor, nat' ~~ ' ~ ~ 0.0169 ~~, . ~ 0.050%
" 3,.,.,:,a",."...., , ,. ; <
;::~x:a~;rvr~~:~"-;:ors; ;,~., ,,.~",::,.", "y.,. O
12 Sucralose '~ ~ i," " f 0.0100 'Y~~~ ~. W. .~*.== 0.029 /0
13 FD&C Red #40 ~s~::~ ' 0.0025 ~ ~~:,t,, -, ."~ := 0.007%
Wei tit ' 23:0633; ~ ~i~F,~' ~7 $33°~a::
r~- ;:Total wei ht 34 0000 . r;~ ,~'~~."100 0~1~%
One 34 g serving of the supplemental dietary composition of Example 3 may be
consumed once a day, preferably on workout days and 45 minutes before a high
intensity workout.
23
CA 02516678 2005-08-18
The supplement of Example 3 may also include the following excipients added,
e.g., during the manufacturing process:
ox_..~ ~ .n ;. a .. ~ redient' ~.zg_._ ~r~.Fomiula
~a P 'ma In re~l~e~.=.~b .
a ~ ~: _~ Se~onr~a . ~~E~t
n redient Qt' m. Prim r ,~~,.,~ y . (g)
~. . . ra. ~Y _ ._ 1 . I ~-
. J .~ _ ~~ .
~
'Prosweet flavor,dextrose 90 - 99%
nat
natural flavor 1 - 10%
ZFruit Punch flavor,maltodextrin
N&A
modified food
starch
corn s ru solids
N&A flavor
3Red spectra flecksum arabic 99.6 - 99.7%
FD&C Red #40 0.3 - 0.4%
4Bitter mask flavor,maltodextrin 96% 0.0648
nat
natural flavors 3% 0.0020
um acacia 1 % 0.0007
50range flavor, maltodextrin 47% 0.0169
nat
silicon dioxide 35% 0.0059
citric acid 14% 0.0024
natural flavors 4% 0.0007
* 10.18 g of granulated GAKIC is supplied by 11.4382 g of 89% granulated GAKIC
with 4% polyvinylpyrrolidone
(PVP, Providone K-30)
** 0.001 g of nanomilled GAKIC is supplied by 0.0011 g of 89% nanomilled GAKIC
with 4% polyvinylpyrrolidone
(PVP, Providone K-30)
24
CA 02516678 2005-08-18
Example 4
L-arginine, calcium keto isocaproic acid, and L-glycine are grinded and
blended
into a premix, which is transferred into a fluid bed for granulation. Air is
blown into the
premix, and 7 % PVP in water solution is added to the premix. The mixture is
form
granulated with final PVP at %, and the granules are dried in a granulator and
transferred to a screener. The granules are collected using a mesh size of 20-
80,
checked for uniformity/homogeneity, and then aliquoted into a serving for
formulation
into a powered beverage mix, tablet, caplet or ready-to-drink beverage
product.
