Note: Descriptions are shown in the official language in which they were submitted.
CA 02682589 2009-10-01
WO 2008/122098 PCT/CA2007/000545
Composition for Promoting the Maintenance and Function
of Muscle-Specific Progenitor Cells
Field of the Invention
[001] The present invention is directed towards a composition and method
for inducing muscle hypertrophy via satellite cells fusion to muscle fibres
and for
inducing a substantially simultaneous replenishment of myogenic precursor
cells in
response to exercise.
Background of the Invention
[002] Body composition, including muscle, is influenced both by genetic
factors and environmental stimuli. Important environmental factors or stimuli
which
effect muscle metabolism include food intake and exercise (Rennie MJ. Body
maintenance and repair: how food and exercise keep the musculoskeletal system
in
good shape. Exp Physiol. 2005 Jul;90(4):427-36). Gene and protein expression
patterns change in response to stimuli. This results in muscle adaptations
such as
muscle atrophy (loss) or muscle hypertrophy (gain). The determination of
muscle
loss or gain is the net effect of both positive and negative factors governing
muscle
development.
[003] `True' muscle hypertrophy can be defined as "as an increase in fiber
diameter without an apparent increase in the number of muscle fibers,
accompanied
by enhanced protein synthesis and augmented contractile force" (Sartorelli V,
Fulco
M. Molecular and cellular determinants of skeletal muscle atrophy and
hypertrophy.
Sci STKE. 2004 Jul 27;2004(244):rel1). However, postnatal muscle growth is
known
to involve both myofiber hypertrophy and increased numbers of myonuclei - the
source of which are satellite cells (Olsen S, Aagaard P, Kadi F, Tufekovic G,
Verney
J, Olesen JL, Suetta C, Kjaer M. Creatine supplementation augments the
increase in
satellite cell and myonuclei number in human skeletal muscle induced by
strength
training. J Physiol. 2006 Jun 1;573(Pt 2):525-34). The growth in the size of
muscles
after birth is, in reality, a combination of an increase in the actual
diameter of a given
muscle fiber and an increase in the number of mononuclei.
[004] Satellite cells are a small population of quiescent muscle precursor
cells that occupy a "satellite" position immediately outside of muscle fibers
(Mauro
1
CA 02682589 2009-10-01
WO 2008/122098 PCT/CA2007/000545
A. Satellite cell of skeletal muscle fibers. J Biophys Biochem Cytol. 1961
Feb;9:493-
5). They are normally maintained in a quiescent state and become activated to
fulfill
roles of routine maintenance, repair and hypertrophy. Satellite cells are
thought to be
muscle-specific stem cells which are capable of producing large numbers of
differentiated progeny as well as being capable of self-renewal (Collins CA,
Partridge
TA. Self-renewal of the adult skeletal muscle satellite cell. Cell Cycle. 2005
Oct;4(10):1338-41). In order that satellite cells can fulfill their biological
role, they
must become activated, proliferate, differentiate and fuse to existing muscle
cells
(Anderson JE. The satellite cell as a companion in skeletal muscle plasticity:
currency, conveyance, clue, connector and colander. J Exp Biol. 2006
Jun;209(Pt
12):2276-92). In this way, multinucleate muscle fibers are maintained or
increased in
size in response to stimuli.
[005] Activation of satellite cells is essential for their proper function and
is
defined as "an entry into G1 from quiescence and mobilization" (Anderson JE,
Wozniak AC. Satellite cell activation on fibers: modeling events in vivo--an
invited
review. Can J Physiol Pharmacol. 2004 May;82(5):300-10). One of the main
factors
which has been associated with the activation of satellite cells is nitric
oxide (NO)
(Anderson JE, Wozniak AC. Satellite cell activation on fibers: modeling events
in
vivo--an invited review. Can J Physiol Pharmacol. 2004 May;82(5):300-10). NO
is a
small, freely diffusible signaling molecule produced in muscle by neuronal NO-
synthase. NO release is regulated by stretching in skeletal muscle and is
thought to be
responsible for early satellite cell activation in response to muscle injury
in proximal
and distal muscle fibers (Anderson JE. A role for nitric oxide in muscle
repair: nitric
oxide-mediated activation of muscle satellite cells. Mol Biol Cell. 2000
May;11(5):1859-74).
[006] NO activity is largely controlled by regulating the enzymes responsible
for synthesizing NO - Nitric Oxide Synthases (NOSs). All major nitric oxide
synthase
(NOS) isoforms and splice variants, including a muscle-specific splice
variant, are
expressed in the skeletal muscles of all mammals (Stamler JS, Meissner G.
Physiology of nitric oxide in skeletal muscle. Physiol Rev. 2001 Jan;81(1):209-
237).
Furthermore, the inner lining, or endothelium, of blood vessels uses NO to
signal the
surrounding smooth muscle to relax. This has the effect of dilating the artery
thereby
increasing blood flow in the affected region.
2
CA 02682589 2009-10-01
WO 2008/122098 PCT/CA2007/000545
[007] NO has also been shown to play an important role in myoblast and
satellite cell fusion (Pisconti A, Brunelli S, Di Padova M, De Palma C,
Deponti D,
Baesso S, Sartorelli V, Cossu G, Clementi E. Follistatin induction by nitric
oxide through cyclic GMP: a tightly regulated signaling pathway that controls
myoblast fusion. J Cell Biol. 2006 Jan 16;172(2):233-44) thereby contributing
to
muscle maintenance and growth. Myoblast fusion is itself a complex process
involving migration, recognition and adhesion, each involving several
mechanisms
and factors.
[008] If stem cells are to function properly, their pools must be maintained.
Therefore, a defining feature of stem cells is their ability of self-renewal
in addition to
being able to produce differentiated cells (Collins CA, Partridge TA. Self-
renewal of
the adult skeletal muscle satellite cell. Cell Cycle. 2005 Oct;4(10):1338-41).
Research has shown that the pool of satellite cells is maintained not only by
self-
renewal but also by contributions from the hematopoietic, i.e. blood, system
(Doyonnas R, LaBarge MA, Sacco A, Charlton C, Blau HM. Hematopoietic
contribution to skeletal muscle regeneration by myelomonocytic precursors.
Proc Natl
Acad Sci U S A. 2004 Sep 14;101(37):13507-12).
[009] In the case where hematopoietic stem cells contribute to muscle
maintenance, the cells must migrate to the area at which they are required for
repair or
maintenance. This directed migration of stem/progenitor cells is termed
`mobilization'. A main mechanism for the mobilization of stem cells is through
the
release of signaling molecules at the site of the stem cell requirement
wherein the
stem cells express the corresponding cell surface receptors (Papayannopoulou
T.
Current mechanistic scenarios in hematopoietic stem/progenitor cell
mobilization.
Blood. 2004 Mar 1;103(5):1580-5). An important receptor-ligand system for the
relationship between the hematopoietic and muscle systems is the CXCR-4
receptor
and the secreted chemokine, SDF-1 (Ratajczak MZ, Majka M, Kucia M, Drukala J,
Pietrzkowski Z, Peiper S, Janowska-Wieczorek A Expression of functional CXCR4
by muscle satellite cells and secretion of SDF-1 by muscle-derived fibroblasts
is
associated with the presence of both muscle progenitors in bone marrow and
hematopoietic stem/progenitor cells in muscles. Stem Cells. 2003;21(3):363-
71).
[0010] The foregoing disclosure describes a composition and method for
stimulating the aforementioned for purposes of muscle hypertrophy in a mammal.
3
CA 02682589 2009-10-01
WO 2008/122098 PCT/CA2007/000545
Summary of the Invention
[0011] The present invention comprises, in accordance with an embodiment
thereof, the administration, to a mammal, of a composition comprising at least
creatine or pharmaceutically acceptable derivatives of creatine such as salts
and esters
of creatine and a source of fucoidan, to induce muscle hypertrophy via
satellite cell
fusion to muscle fibres and to provide substantially coincident support for
the
replenishment of myogenic precursor cells in response to exercise.
Detailed Description of the Invention
[0012] In the following description, for the purposes of explanations,
numerous specific details are set forth in order to provide a thorough
understanding of
the present invention. It will be apparent, however, to one of ordinary skill
in the art
that the present invention may be practiced without these specific details.
[0013] The present invention is directed towards inducing muscle hypertrophy
via satellite cell fusion to muscle fibres and provide substantially
coincident support
for the replenishment of myogenic precursor cells in response to exercise. The
composition and method of the present invention accomplishes said support by
encouraging multiple distinct aspects of muscle-specific progenitor cell
biology.
[0014] As used herein, the term "muscle-specific progenitor cell" refers to
any
undifferentiated cell that is, or will be, at any time, capable of
differentiating into any
cell type which contributes to mature, functional adult skeletal muscle. This,
for the
purposes of the present disclosure, includes satellite cells and any other
multi-potent
cells such as hematopoietic stem cells which have the potential to contribute
to
skeletal muscle hypertrophy and growth, development or maintenance. It is
herein
understood that, despite a lack of consensus regarding nomenclature, there
exists a
continuum of cell types that lie between a classical pluripotent `embryonic
stem cell'
capable of giving rise to all cell types on one extreme and a terminally-
differentiated
cell on the other extreme. It is herein understood that a number of
undifferentiated cell
types having increasingly limited developmental potential progressing from an
embryonic stem cell toward a terminally-differentiated cell exist between said
extremes. Furthermore, it is herein understood that such undifferentiated
cells with
limited, yet still multiple, developmental possibilities are generally termed
`tissue-
4
CA 02682589 2009-10-01
WO 2008/122098 PCT/CA2007/000545
specific stem cells'. However, undifferentiated cells with only one
developmental
possibility are generally termed `progenitor cells'.
[0015] Ingredients of the present composition may also be fine-milled in order
to improve the immediacy of absorption, and thus the rate of bioavailability
upon
consumption by an individual. The fine-milling techniques and the immediacy of
absorption employed in the present invention are disclosed in U.S. Patent
Application
No. 11/709,526, entitled "Method For Increasing The Rate And Consistency Of
Bioavailability Of Supplemental Dietary Ingredients" and U.S. Patent
Application No.
11/709,525, entitled "Method for a Supplemental Dietary Composition Having a
Multi-Phase Dissolution Profile," both herein incorporated fully by reference.
Briefly, rate of bioavailability is increased via a narrowing of particle size
range and a
concomitant reduction in the average particle size, improving the immediacy of
absorption of said supplemental dietary ingredient. Furthermore, the
consistency of
dissolution, and thus the absorption of orally administered supplemental
dietary
ingredients, is improved by the fine-milled process.
[0016] As used herein, the term "fine-milled" and/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 a reduction in the
size of the
particle. The force, in the case of micronization may be applied in any manner
such
as, e.g., the collision of particles at high rates of speed, grinding, or by
an air-jet
micronizer. In a preferred embodiment, fine-milled particles are obtained by
jet-
milling with nitrogen and compressed air.
[0017] As used herein, the term "particle size" refers to the diameter of the
particle. 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 given sample will have the specified particle size. For the
purposes
of the present invention, the preferred particle size range for fine-milled
particles is
between 2 and 50 microns.
[0018] The size of a particle can be determined by any of the methods known
within the art. Methods for particle size determination which may be employed
are,
for example, sieves, sedimentation, electrozone sensing (Coulter counter),
5
CA 02682589 2009-10-01
WO 2008/122098 PCT/CA2007/000545
microscopy, and/or Low Angle Laser Light Scattering. The preferred methods for
the
particle size determination of the present invention are the methods which are
most
commonly used in the pharmaceutical industry, such as laser diffraction, e.g.,
via light
scattering Coulter Delsa 440SX.
[0019] The fine-milling process may be employed in the processing of one or
more of the ingredients of the present invention in the dosage forms of
tablets, e.g.,
immediate-release film coated, modified-release and fast-dissolving; capsules,
e.g.,
immediate-release and modified-release; liquid dispersions; powders; drink
mixes,
etc.
Creatine
[0020] Creatine use has been thoroughly studied and is well-established as a
beneficial dietary supplement for replenishing energy stores in working muscle
cells
(Greenhaff PL, Bodin K, Soderlund K, Hultman E. Effect of oral creatine
supplementation on skeletal muscle phosphocreatine resynthesis. Am J Physiol.
1994
May;266(5 Pt 1):E725-30). The resultant increase in muscular energy stores
from
creatine supplementation in an individual, combined with physical exercise
leads to
increased strength, and a reduction in fatigue resulting from high-intensity
exercise
(Greenhaff PL, Casey A, Short AH, Harris R, Soderlund K, Hultman E. Influence
of
oral creatine supplementation of muscle torque during repeated bouts of
maximal
voluntary exercise in man. Clin Sci (Lond). 1993 May;84(5):565-71) as well as
increasing muscle growth (Volek JS, Duncan ND, Mazzetti SA, Staron RS,
Putukian
M, Gomez AL, Pearson DR, Fink WJ, Kraemer WJ. Performance and muscle fiber
adaptations to creatine supplementation and heavy resistance training. Med Sci
Sports
Exerc. 1999 Aug;31(8):1147-56).
[0021] More recently however, creatine supplementation has been shown to
augment the increase in satellite cell numbers in response to exercise (Olsen
S,
Aagaard P, Kadi F, Tufekovic G, Verney J, Olesen JL, Suetta C, Kjaer M.
Creatine
supplementation augments the increase in satellite cell and myonuclei number
in
human skeletal muscle induced by strength training. J Physiol. 2006 Jun
1;573(Pt
2):525-34). Furthermore, it was suggested by the results of Olsen et al., that
the rate
of fusion of satellite cells was also increased in response to creatine
supplementation
and exercise, adding to an observed increase in the size of muscle fibers.
6
CA 02682589 2009-10-01
WO 2008/122098 PCT/CA2007/000545
[0022] In various embodiments of the present invention, which are set forth in
greater detail in Examples 1 to 4 below, the supplemental composition
comprises
creatine or derivatives thereof. A serving of the supplemental composition
comprises
from about 1.00 g to about 10.00 g of creatine or derivatives thereof. The
preferred
dosage of a serving of the supplemental composition of the present invention
comprises about 3.50 g of creatine or pharmaceutically acceptable derivatives
of
creatine such as salts and esters of creatine.
[0023] For example, the creatine may be present in various embodiments of
the present invention as creatine salts of malate, maleate, fumarate,
tartrate, citrate,
succinate, pyruvate, pyroglutamate, glutamate or any other pharmaceutically
acceptable salt as known in the art.
[0024] Additionally or alternatively, the creatine may be present in various
embodiments of the present invention as creatine esters of phosphate, sulphate
or any
other pharmaceutically acceptable esters as known in the art.
[0025] The present invention, as set forth in greater detail in Example 4
below, may further comprise creatine pyroglutamate as a pharmaceutically
acceptable
derivative of creatine. A serving of the supplemental composition may comprise
from
about 0.005 g to about 0.10 g of creatine pryoglutamate. The preferred dosage
of a
serving of the supplemental composition comprises about 0.01 g of creatine
pyroglutamate.
[0026] The present invention may further comprise at least a portion of the
creatine or pharmaceutically acceptable salts or esters thereof in a fine-
milled format.
In various embodiments of the present invention, the supplemental composition
comprises fine-milled creatine or pharmaceutically acceptable salts or esters
of said
creatine. A serving of the supplemental composition comprises from about 0.005
g to
about 0.05 g of fine-milled creatine or pharmaceutically acceptable salts or
esters of
said creatine. The preferred dosage of a serving of the supplemental
composition
comprises about 0.02 g of fine-milled creatine or pharmaceutically acceptable
salts or
esters of said creatine.
Fucoidan
[0027] Fucoidans are naturally-occurring sulfated sugar polymers. They are
constituents of edible seaweed and have been consumed by humans for centuries.
7
CA 02682589 2009-10-01
WO 2008/122098 PCT/CA2007/000545
The specific type of fucoidan differs dependent upon the source. Brown
seaweed, in
particular, is a source of branched-chain Fucoidans and several species have
been
used experimentally as a source of Fucoidans including Fucus vesiculosus,
Undaria
pinnatifida and Laminaria japonica. One of the main and earliest mechanisms
elucidated for the activity of Fucoidans has been the binding with L- and P-
selectin,
members of a family of cell surface receptors involved in the inflammatory
response.
The selectins mediate the binding and adhesion of cells expressing the
selectins to
other cells such as those on the endothelium upon cytokine activation
(Bevilacqua
MP, Nelson RM. Selectins. J Clin Invest. 1993 Feb;91(2):379-87).
[0028] A number of potential beneficial uses have been suggested for
Fucoidan (Berteau 0, Mulloy B. Sulfated fucans, fresh perspectives:
structures,
functions, and biological properties of sulfated fucans and an overview of
enzymes
active toward this class of polysaccharide. Glycobiology. 2003 Jun;13(6):29R-
40R).
Fucoidan has been shown to have immunomodulating effects by stimulating
lymphocytes and macrophages (Choi EM, Kim AJ, Kim YO, Hwang JK.
Immunomodulating activity of arabinogalactan and fucoidan in vitro. J Med
Food.
2005 Winter;8(4):446-53). As well, Herpes virus reactivation can be inhibited
by
treatment with Fucoidan (Cooper R, Dragar C, Elliot K, Fitton JH, Godwin J,
Thompson K. GFS, a preparation of Tasmanian Undaria pinnatifida is associated
with
healing and inhibition of reactivation of Herpes. BMC Complement Altern Med.
2002
Nov 20;2:11). Importantly, orally administered Fucoidan in humans has been
shown
to increase the number of CXCR-4-expressing stem cells which can replenish the
pool
of satellite cells (Irhimeh MR et al. Fucoidan and CXCR4+ hemopoietic
progenitor
stem cell population, 2004, The Sydney Convention Centre North, Darling
Harbour,
Australian StemCell Centre). Furthermore, fucoidan can induce the mobilization
of
these stem cells to muscles (Sweeney EA, Priestley GV, Nakamoto B, Collins RG,
Beaudet AL, Papayannopoulou T. Mobilization of stem/progenitor cells by
sulfated
polysaccharides does not require selectin presence. Proc Natl Acad Sci U S A.
2000
Jun 6;97(12):6544-9). This effect is most likely due to the observed effect of
increasing SDF-1 plasma levels (Sweeney EA, Lortat-Jacob H, Priestley GV,
Nakamoto B, Papayannopoulou T. Sulfated polysaccharides increase plasma levels
of
SDF-1 in monkeys and mice: involvement in mobilization of stem/progenitor
cells.
Blood. 2002 Jan 1;99(1):44-51).
8
CA 02682589 2009-10-01
WO 2008/122098 PCT/CA2007/000545
[0029] In a preferred embodiment of the present invention, the supplemental
composition comprises fucoidan. A serving of the supplemental composition
comprises from about 0.01 g to about 0.1 g of fucoidan. The preferred dosage
of a
serving of the supplemental composition of the present invention comprises
about
0.024 g of fucoidan.
[0030] In various embodiments of the present invention, which are set forth in
greater detail in Examples 1 to 4 below, the supplemental composition
comprises
Laminariajaponica extract as a source of fucoidan.
Sphinoglipids
[0031] Sphingolipids are important constituents of eukaryotic organisms.
Complex sphingolipids and their metabolic products are highly bioactive
molecules
which are involved in the regulation of many important biological functions
including
cell growth, differentiation and apoptosis (Vesper H, Schmelz EM, Nikolova-
Karakashian MN, Dillehay DL, Lynch DV, Merrill AH Jr. Sphingolipids in food
and
the emerging importance of sphingolipids to nutrition. J Nutr. 1999
Ju1;129(7):1239-
50). Sphingolipid metabolism and biological function can be modulated by
dietary
intake of sphingolipids. Supplying supplemental sphingolipids promotes the
synthesis
of sphingosine 1-phosphate.
[0032] Sphingosine 1-phosphate is a bioactive sphingolipid metabolite that
has been shown to regulate a number of important biological functions
including
satellite cell activation (Nagata Y, Partridge TA, Matsuda R, Zammit PS. Entry
of
muscle satellite cells into the cell cycle requires sphingolipid signaling. J
Cell Biol.
2006 Jul 17;174(2):245-53) and myogenic differentiation (Donati C, Meacci E,
Nuti
F, Becciolini L, Farnararo M, Bruni P. Sphingosine 1-phosphate regulates
myogenic
differentiation: a major role for S1P2 receptor. FASEB J. 2005 Mar;19(3):449-
51),
both of which are processes important for increasing muscle hypertrophy.
[0033] In embodiments of the present invention, which are set forth in greater
detail in Examples 2 to 4 below, the supplemental composition comprises a
source of
sphingolipids. A serving of the supplemental composition of the present
invention
comprises from about 0.005 g to about 0.05 g of a source of sphingolipids. The
preferred dosage of a serving of the supplemental composition of the present
invention comprises about 0.014 g of a source of sphingolipids.
9
CA 02682589 2009-10-01
WO 2008/122098 PCT/CA2007/000545
Resveratrol
[0034] Resveratrol is a polyphenol found in many plant sources, most notably
in grape skins, grape juice and red wine. One of the most abundant sources is
from
the roots of Polygonum cuspidatum. In plants, the biological function of
resveratrol is
as an antibiotic to fight infection. However, as a component of the diet,
either as a
constituent of plant-based foods or as a nutritional supplement, resveratrol
has been
reported to confer many health benefits. The main beneficial function of
polyphenols
from plant sources is generally attributed to antioxidant activity. However,
resveratrol has been shown to increase NO production by tissue-specific
induction of
NOSs (Das S, Alagappan VK, Bagchi D, Sharma HS, Maulik N, Das DK.
Coordinated induction of iNOS-VEGF-KDR-eNOS after resveratrol consumption: a
potential mechanism for resveratrol preconditioning of the heart. Vascul
Pharmacol.
2005 Apr-May;42(5-6):281-9 Abstract).
[0035] In various embodiments of the present invention, which are set forth in
greater detail in Examples 3 and 4 below, the supplemental composition of the
present
invention comprises Polygonum cuspidatum as a source of resveratrol. A serving
of
the supplemental composition of the present invention comprises from about
0.001 g
to about 0.01 g of Polygonum cuspidatum as a source of resveratrol. The
preferred
dosage of a serving of the supplemental composition of the present invention
comprises about 0.004 g of Polygonum cuspidatum as a source of resveratrol.
[0036] In a preferred embodiment of the present invention, the composition of
the present invention comprises at least creatine or pharmaceutically
acceptable
derivatives of creatine such as salts and esters of creatine and a source of
fucoidan.
[0037] In another embodiment of the present invention, the composition of the
present invention comprises creatine or pharmaceutically acceptable
derivatives of
creatine such as salts and esters of creatine, a source of fucoidan and a
source of
sphingolipids.
[0038] In yet another embodiment of the present invention, the composition of
the present invention comprises creatine or pharmaceutically acceptable
derivatives of
creatine such as salts and esters of creatine, a source of fucoidan, a source
of
sphinoglipids and a source of resveratrol.
CA 02682589 2009-10-01
WO 2008/122098 PCT/CA2007/000545
[0039] The compositions of the present invention may also comprise, in
addition to the aforementioned constituents, any number of amino acids in
sufficient
quantities to be effective in inducing muscle hypertrophy, or salts or esters
of said
amino acids. For example, proteins, such as whey protein, casein protein, milk
proteins, or soy protein, may further be included in the compositions of the
present
invention in quantities effective to induce muscle hypertrophy. Amino acids
and
proteins are well known in the art to aid in the generation and repair of
muscle
protein.
[0040] Not wishing to be bound by theory, it is believed that the various
components of the present invention will act via multiple, distinct biological
pathways
to aid in the maintenance and function of myogenic precursor cells in repair
and
growth of skeletal muscle. The composition of the present invention, when used
in
conjunction with the method provided herein, induces muscle hypertrophy via
satellite cells fusion to muscle fibres and induces the substantially
simultaneous
replenishment of myogenic precursor cell in response to exercise.
[0041] Additionally, by way of ingestion of the composition of the present
invention, a method for enhancing the effectiveness of the immune system in an
individual is provided. The method of the present invention comprises at least
the
step of administering to an individual a therapeutically effective and
acceptable
amount of the composition of the present invention.
[0042] According to additional methods, the compositions of the present
invention may be administered to a mammal via any therapeutically acceptable
format. For example, the compositions of the present invention may be
administered
to a mammal intravenously, intramuscularly, or interperitoneally as routes of
administration distinct from the aforementioned oral method. These instantly
disclosed routes of administration may also be combined with an oral
administration
of the composition of the present invention as an additional method of
administration
to a mammal.
[0043] According to various embodiments of the present invention, the
nutritional supplement may be consumed in any form. For instance, the dosage
form
of the nutritional supplement may be provided as, e.g., a powder beverage mix,
a
liquid beverage, a ready-to-eat bar or drink product, a capsule, a liquid
capsule, a
11
CA 02682589 2009-10-01
WO 2008/122098 PCT/CA2007/000545
tablet, a caplet, or as a dietary gel. The preferred dosage forms of the
present
invention are as a caplet or as a liquid capsule. The present composition may
also be
provided in various time-release formats, e.g. a slow-release format, a quick-
release
format, or a phase-release format, as are known in the art as well.
[0044] Furthermore, the dosage form of the nutritional supplement may be
provided in accordance with customary processing techniques for herbal and
nutritional supplements in any of the forms mentioned above. Additionally, the
nutritional supplement set forth in the example embodiments herein may contain
any
appropriate number and type of excipients, as is well known in the art.
[0045] The present nutritional composition or those similarly envisioned by
one of skill in the art, may be utilized in methods to support the biological
function of
muscle-specific progenitor cells required for skeletal muscle recovery and
growth in
response to exercise. Specifically, the present compositions and method
disclosed
herein are provided to induce muscle hypertrophy via satellite cell fusion to
muscle
fibres and induce a substantially coincident replenishment of myogenic
precursor cell
in response to exercise.
[0046] Although the following examples illustrates the practice of the present
invention in several of its embodiments, the examples should not be construed
as
limiting the scope of the invention. Other embodiments will be apparent to one
of
skill in the art from consideration of the specifications and examples.
12
CA 02682589 2009-10-01
WO 2008/122098 PCT/CA2007/000545
Examples
Example 1
[0047] A nutritional supplement for inducing muscle hypertrophy via satellite
cell fusion to muscle fibres and inducing a substantially simultaneous
replenishment
of myogenic precursor cell in response to exercise is provided. The
nutritional
supplement is in the form of caplets. One serving of the nutritional
supplement is 7
caplets and each serving comprises:
[0048] about 3.5 g of creatine monohydrate (fine-milled), and about 0.024 g
of Laminaria japonica extract (standardized to 85% fucoidan).
Example 2
[0049] A nutritional supplement for inducing muscle hypertrophy via satellite
cells fusion to muscle fibres and inducing a substantially simultaneous
replenishment
of myogenic precursor cell in response to exercise is provided. The
nutritional
supplement is in the form of caplets. One serving of the nutritional
supplement is 7
caplets and each serving comprises:
[0050] about 3.5 g of creatine monohydrate (fine-milled), about 0.024 g of
Laminaria japonica extract (standardized to 85% fucoidan), and about 0.0145 g
of
soy/milk sphingolipids.
Example 3
[0051] A nutritional supplement for inducing muscle hypertrophy via satellite
cells fusion to muscle fibres and inducing a substantially simultaneous
replenishment
of myogenic precursor cell in response to exercise is provided. The
nutritional
supplement is in the form of caplets. One serving of the nutritional
supplement is 7
caplets and each serving comprises:
[0052] about 3.5 g of creatine monohydrate (fine-milled), about 0.024 g of
Laminaria japonica extract (standardized to 85% fucoidan), about 0.0145 g of
soy/milk sphingolipids, and about 0.004 g of Polygonum cuspidatum,.
Example 4
[0053] A nutritional supplement for inducing muscle hypertrophy via satellite
cells fusion to muscle fibres and inducing a substantially simultaneous
replenishment
13
CA 02682589 2009-10-01
WO 2008/122098 PCT/CA2007/000545
of myogenic precursor cell in response to exercise is provided. The
nutritional
supplement is in the form of caplets. One serving of the nutritional
supplement is 7
caplets and each serving comprises:
[0054] about 2.00 g of creatine monohydrate (fine-milled), about 0.02 g of
creatine monohydrate (nanodiffuse), about 0.01 g of creatine pyroglutamate,
about
1.30 g of creatine citrate, about 0.001 g of creatine malate, about 0.02 g of
creatine
pyruvate, about 0.024 g of Laminaria japonica extract (standardized to 85%
fucoidan), about 0.0145 g of soy/milk sphingolipids, about 0.004 g of
Polygonum
cuspidatum, about 0.05 g of L-glycine ethyl ester, about 2.9 g of L-tyrosine,
about
0.001 g of L-tyrosine methyl ester, and about 0.002 g of Yohimbe.
Extensions and Alternatives
[0055] In the foregoing specification, the invention has been described with
specific embodiments thereof. However, it will be evident that various
modifications
and changes may be made thereto without departing from the broader spirit and
scope
of the invention.
14
