Note: Descriptions are shown in the official language in which they were submitted.
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KITS AND METHODS FOR OPTIMIZING THE EFFICACY OF
CHONDROPROTECTIVE COMPOSITIONS
FIELD OF THE INVENTION
The present invention is directed to kits which are useful for promoting one
or more
health benefits including, for example, joint health, bone health, cardiac
health, and / or anti-
inflammation. The present invention is further directed to methods of using
the kits.
BACKGROUND OF THE INVENTION
Osteoarthritis is a widespread, degenerative disease of the joints, cartilage,
and other
articular components. Osteoarthritis affects all ethnic groups worldwide. In
addition to humans,
osteoarthritis affects nearly all mammals, for example, horses and cows, as
well as domestic cats
and dogs. Many treatments for osteoarthritis have been proposed, all resulting
in varying
degrees of success.
One osteoarthritis treatment which has been recently proposed is oral
administration of
chondroprotective agents such as glucosamine and / or chondroitin. See e.a.,
Henderson, U.S.
Patent No. 5,364,845, assigned to Nutramax Laboratories, issued November 15,
1994. Indeed,
various commercial products are available in the marketplace, including
nutritional supplements
containing such agents and powders which may be formulated into beverage
compositions
immediately prior to use.
Typically, administration of such agents is designed to enhance' proteoglycan
through an
increased concentration of glycosaminoglycans. Enhanced proteoglycan provides
the framework
for collagen and other joint components, as well as imparting flexibility,
resiliency, and resistance
to compression. Thus, these agents may be administered according to various
methods to
enhance the articular compositions or, at a minimum, inhibit the process of
degradation.
The readily available compositions containing various chondroprotective agents
are in
dry-form, for example, in the form of tablets or capsules. These forms offer
the benefit of
enhancing joint or bone health, however, the forms also suffer various
deficiencies. For example,
these dry-forms are not convenient for use and are not beneficial for
compliance to a particular
regimen. Moreover, some dry-forms require formulation in water by the
consumer, which
introduces the 'elements of dosing errors and contamination. Other forms
include aqueous
"syrups" (e.g., highly concentrated compositions) which are also inconvenient,
particularly
unpalatable, and thus do not promote compliance to an effective regimen.
The present inventors have surprisingly discovered that the efficacy of the
chondroprotective agent is dependent upon two factors: 1 ) the form of the
chondroprotective
composition (i.e., whether in dry-form, syrup-form, or ready-to-drink form);
and 2) whether the
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composition is ingested at or near the time of ingestion of a food or
beverage. Excitingly, the
present inventors have discovered that efficacy of the chondroprotective
composition is enhanced
wherein the composition is ingested within about 4 hours of ingestion of a
food or beverage,
relative to not consuming a food or beverage during this time period. In
addition to this finding, it
has been surprisingly discovered that the efficacy of aqueous
chondroprotective compositions is
significantly greater relative to that of dry-forms and syrup-forms of
chondroprotective
compositions (e.g., tablets or capsules), even wherein each of these
compositions is ingested
within about 4 hours of ingestion of a food or beverage.
Accordingly, efficacy of chondroprotective compositions is surprisingly
related to behavior
of the consumer in need of treatment, in particular, the relationship between
1 ) ingestion of a
particular form of chondroprotective composition; and 2) food or beverage
intake.
Consistent with this discovery, the present inventors describe herein kits
which comprise
a ready-to-drink chondroprotective composition as well as information which,
when followed,
improves or aids efficacy of the composition. In particular, the kits comprise
information which
instructs or suggests ingestion of the composition within about 4 hours of
ingestion of a food or
beverage. Alternatively or additionally, the kits comprise information which
informs the consumer
that aqueous chondroprotective compositions provide enhanced efficacy relative
to dry-form and /
or syrup-form chondroprotective compositions having the same, or similar,
chondroprotective
agent. Methods of administering the present compositions within about 4 hours
of administration
of a food or beverage, such that an enhanced health benefit is realized, are
also provided.
SUMMARY OF THE INVENTION
The present invention is directed to kits which are useful for promoting one
or more
health benefits as defined herein. In particular, the present kits comprise:
(a) a composition comprising one or more chondroprotective agents and at least
about
80% water; and
(b) information selected from the group consisting of:
(i) dose-form information;
(ii) instruction or suggestion of ingestion of the composition within about 4
hours of
ingestion of a food or beverage; and
(iii) combinations thereof.
Most preferably, the instruction or suggestion relates to ingestion within
about 2 hours or
concurrently with a food or beverage.
The present invention is further directed to kits comprising:
(a) a composition comprising one or more chondroprotective agents and at least
about
80% water; and
(b) a separate food or beverage.
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Consistent with this discovery, the present invention also relates to methods
of enhancing
a benefit associated with a composition comprising one or more
chondroprotective agents and
water, the method comprising administering to a mammal the composition within
about 4 hours of
administration of a food or beverage.
DETAILED DESCRIPTION OF THE INVENTION
The present invention is directed to kits which are useful for providing
chondroprotective
compositions having enhanced health benefits, and instructions or suggestions
for use which
encourage optimization of these benefits. Wherein this regimen is followed,
compliance, and thus
efficacy, is enhanced. The compositions include those which are traditional,
as well as those
which may be classified as "medical foods" under regulatory guidelines.
Preferably, the
composition is a beverage composition. The present invention is further
directed to methods of
using such compositions.
The compositions are suitable for mammalian use, particularly use in humans
and
domestic animals such as, for example, dogs, cats, horses, and cows.
Publications and patents are referred to throughout this disclosure. All
references cited
herein are hereby incorporated by reference.
All percentages and ratios are calculated by weight unless otherwise
indicated. All
percentages and ratios are calculated based on the total composition unless
otherwise indicated.
All component or composition levels are in reference to the active level of
that component
or composition, and are exclusive of impurities, for example, residual
solvents or by-products,
which may be present in commercially available sources.
Referred to herein are trade names for components including various
ingredients utilized
in the present invention. The inventors herein do not intend to be limited by
materials under a
certain trade name. Equivalent materials (e.g., those obtained from a
different source under a
different name or catalog (reference) number) to those referenced by trade
name may be
substituted and utilized in the compositions, kits, and methods herein.
In the description of the invention various embodiments and / or individual
features are
disclosed. As will be apparent to the ordinarily skilled practitioner, all
combinations of such
embodiments and features are possible and can result in preferred executions
of the present
invention.
The compositions, kits, and methods herein may comprise, consist essentially
of, or
consist of any of the elements as described herein.
Kits of the Present Invention
The kits of the present invention are useful for providing one or more
enhanced health
benefits, including, for example, joint health, bone health, cardiac health,
anti-inflammation and /
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or efficacy benefits. Joint health benefits include, but are not limited to,
preventing, inhibiting,
ceasing and l or reversing the actions associated with arthritis, particularly
osteoarthritis. Thus,
improved joint health will provide, for example, decreased pain in the joints
and / or increased
flexibility. Bone health benefits include, but are not limited to, preventing,
inhibiting, ceasing, and /
or reversing bone loss and / or building bone mass, and ! or preventing,
inhibiting, ceasing, and
or reversing osteoporosis. Thus, improved bone health may provide, for
example, healthy bones,
stronger bones, and / or increased bone mass. Cardiac health benefits include,
but are not
limited to, preventing, inhibiting, ceasing, and / or reversing, for example,
heart disease,
atherosclerosis, and / or restenosis. Anti-inflammation benefits include, for
example, preventing,
inhibiting, ceasing, and / or reversing inflammation, particularly in the
joints. Thus, anti-
inflammation will typically result in pain reduction. Efficacy benefits are
included within all of the
foregoing, and include enhanced efficacy and / or bioavailability in treating,
preventing, and / or
ceasing joint health dysfunction, bone health dysfunction, cardiac health
dysfunction, and / or
inflammation.
In one embodiment of the present invention, the kits comprise:
(a) a composition comprising one or more chondroprotective agents and at least
about
80% water; and
(b) information selected from the group consisting of:
(i) dose-form information;
(ii) instruction or suggestion of ingestion of the composition within about 4
hours of
ingestion of a food or beverage; and
(iii) combinations thereof.
In yet another embodiment of the present invention, the kits comprise:
(a) a composition comprising one or more chondroprotective agents and at least
about
80% water; and
(b) a separate food or beverage.
Each of these various elements of the present invention is described in
considerable detail herein
below. In particular, the compositions used and the information provided is
described.
The Composition Used in the Present Kits and Methods
The present invention is directed to use of compositions which are useful in,
for example,
food, beverage, pharmaceutical, over-the-counter, and dietary supplement
products. The
products are suitable for mammalian use, particularly use in humans and
domestic animals such
as, for example, dogs, cats, horses, and cows. Preferably, the present
compositions are directed
for use in humans and domestic animals. More preferably, the present
compositions are directed
for use in humans, domestic dogs, and domestic cats. Most preferably, the
present compositions
are directed for use in humans.
The present compositions comprise one or more chondroprotective agents and
water:
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A. Chondroprotective Aaent
The chondroprotective agent utilized herein may be any agent which provides
joint
health, bone health, and / or anti-inflammation, as described above. Many of
these agents will
also provide a cardiac health benefit, as also described above.
Chondroprotective agents are
quite well-known in the art, and the ordinarily skilled artisan has the
capability to choose any such
agent for use in the present invention.
Without intending to be limited by theory, the chondroprotective agent is
important for
enhancing joint function as the component aids in the stimulation of
proteoglycan and collagen in
vivo. Proteoglycan provides the connective tissue, for example, collagen,
which is necessary for
joint health. Indeed, proteoglycan is comprised of glycosaminoglycans (often
termed "GAGs")
which are long chains of modified sugars. Aminosugars and
methylsulfonylmethane are useful
for building glycosaminoglycans and proteoglycan. Additionally, the cardiac
benefits of various of
these components is also a beneficial feature of this component. See e.a.,
Morrison et al:,
Coronary Heart Disease and the Mucopolysaccharides (Glycosaminoglycans), pp.
109 - 127
(1973).
Non-limiting examples of chondroprotective agents which are useful herein
include
gelatin, cartilage, aminosugars, glycosaminoglycans, methylsulfonylmethane,
precursors of
methylsulfonylmethane, S-adenosylmethionine, salts thereof, and mixtures
thereof. Preferably,
the chondroprotective agent is selected from gelatin, cartilage, aminosugars,
glycosaminoglycans, S-adenosylmethionine, salts thereof, and mixtures thereof.
More preferably,
the chondroprotective agent is selected from aminosugars, glycosaminoglycans,
S-
adenosylmethionine, salts thereof, and mixtures thereof. Even more preferably,
the
chondroprotective agent is selected from aminosugars, glycosaminoglycans,
salts thereof, and
mixtures thereof. Most preferably, the chondroprotective agent is a salt of an
aminosugar,
particularly wherein the aminosugar is glucosamine.
Examples of these chondroprotective agents, and preferred embodiments thereof,
are
described in expanded detail as follows. With respect to dosing preferences,
all dosage levels
are based on typical human subjects (e.g., a 65 kg subject). Wherein the
present composition is
used in other mammals, it may be necessary to modify the dosage. Modification
of dosages
based on the needs of the subject is well within the skill of the ordinary
artisan. It is therefore
understood that these dosage ranges are by way of example only, and that daily
administration can be adjusted depending on various factors. The specific
dosage of the
chondroprotective agent to be administered, as well as the duration of
treatment are
interdependent. The dosage and treatment regimen will also depend upon such
factors as
the specific chondroprotective agent used, the treatment indication, the
efficacy of the
compound, the personal attributes of the subject (such as, for example,
weight, age, sex,
and medical condition of the subject), and compliance with the treatment
regimen.
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Gelatin
As is commonly known, gelatin is a protein obtained from the partial
hydrolysis of
collagen, which is the major structural and connective protein tissue in
mammals. Gelatin
typically contains from about 84% to about 90% protein, from about 1 % to
about 2% mineral salts,
and from about 8% to about 15% water (these are non-limiting approximations).
Gelatin typically
contains specific amounts of 18 different amino acids, which are joined
together to form
polypeptide chains of approximately 1,000 amino acid residues per chain.
Typically, the collagen obtained for gelatin production is from animal bones
and skins,
e.g., from cows and pigs. Gelatin production will typically involve the
subjection of coilagenous
material to alkaline pre-treatment, followed by hot-water extraction
(providing gelatin having an
iso-electric point of about 5). Acidic pre-treatment may also be utilized
(providing gelatin having
an iso-electric point of from about 7 to 9).
In accordance with the present invention, wherein gelatin is included within a
present
composition, a single dose of gelatin within the composition is preferably
from about 1 mg to
about 2000 mg, more preferably from about 100 mg to about 700 mg, even more
preferably from
about 150 mg to about 600 mg, and most preferably from about 200 mg to about
400 mg.
Typically, the composition comprising the gelatin could be dosed from about
once to about five
times daily, preferably from about once to about three times daily, most
preferably once daily.
Cartilage
Cartilage may be chosen as the chondroprotective agent in the present
compositions. As
is commonly known in the art, cartilage is a tough, elastic tissue present in
the joints (as well as
other locations) of the bodies of various mammals. Cartilage is comprised of
at least one of
calcium, proteins, carbohydate mucopolysaccharides (e.g., chondroitin), and
collagen.
Particularly preferred for use herein is bovine cartilage and shark cartilage.
Bovine
cartilage is primarily derived from the trachea of cows (also known as bovine
tracheal cartilage, or
BTC). It is similar in structure to shark cartilage. Shark cartilage is a
widely utilized cartilage
source, as the skeletons of sharks are primarily composed of cartilage rather
than bone.
In accordance with the present invention, wherein cartilage is included within
a present
composition, a single dose of cartilage within the composition is preferably
from about 1 mg to
about 2000 mg, more preferably from about 100 mg to about 700 mg, even more
preferably from
about 150 mg to about 600 mg, and most preferably from about 200 mg to about
400 mg.
Typically, the composition comprising the cartilage is dosed from about once
to about five times
daily, preferably from about once to about three times daily, most preferably
once daily.
Aminosuaars
One or more aminosugars may be chosen as the chondroprotective agent herein.
The
aminosugars are monosaccharide components (i.e., hexoses) which are modified
with an amine
functionality. The amine functionality may be a free amine moiety or a
protected amine moiety
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(e.g., N-acetyl amine). Preferably, the aminosugar is a precursor to
glycosaminoglycan, which is
important for construction of joint constituents (e.g., collagen).
Additionally, certain aminosugars
may serve to inhibit the activity of enzymes which are implicated in breakdown
the cartilage in
osteoarthritics (e.g., mannosamine, which has been discovered to inhibit
aggrecanase). The
aminosugars are well-known in the art; many aminosugars are naturally
occurring.
Particularly preferred aminosugars include glucosamine, salts of glucosamine,
galactosamine, salts of galactosamine, mannosamine, salts of mannosamine,.as
well as the N-
acetyl derivatives of the foregoing, including N-acetyl glucosamine and N-
acetyl galactosamine.
More preferably, the aminosugars include glucosamine and salts of glucosamine,
most preferably
salts of glucosamine. Particularly preferred salts of glucosamine include
glucosamine sulfate and
glucosamine hydrochloride. The salts of glucosamine are particularly preferred
to aid
bioavailability to the aminosugar in addition to the bioavailability benefit
achieved by the second
component (as described herein below).
As an example, glucosamine provides the building block needed in vivo to
manufacture
glycosaminoglycan, which is found in cartilage. Thus, glucosamine, and other
aminosugars,
function not only to relieve symptoms of joint pain but also inhibits, stops,
and / or reverses the
degenerative process.
Typical single dosing of the aminosugars is preferably from about 1 mg to
about 5000
mg, more preferably from about 100 mg to about 3600 mg, even more preferably
from about 150
mg to about 2200 mg, and most preferably from about 250 mg to about 1900 mg,
based on the
molecular weight of glucosamine hydrochloride. For example, a particularly
preferred dosage of
glucosamine hydrochloride is about 1800 mg, which translates to about 1480 mg
of glucosamine.
All other aminosugars may be similarly dosed, based on the molecular weight of
glucosamine
hydrochloride. Typically, the composition comprising the aminosugar is dosed
from about once to
about five times daily, preferably from about once to about three times daily,
most preferably once
daily.
Glycosaminoalycans
One or more glycosaminoglycans may be utilized as the chondroprotective agent
herein.
The glycosaminoglycans are commonly known as GAGs, and are precursors to joint
structure, for
example, collagen. The glycosaminoglycans may also be important for the
healing of bone.
Suitable glycosaminoglycans will be well-known to the ordinarily skilled
artisan. Preferred
glycosaminoglycans include chondroitin, hyaluronic acid, keratan, heparin, and
dermatin, as well
as salts of the foregoing. For example, chondroitin sulfate is a particularly
preferred chondroitin
salt. As with the aminosugars, salts of the glycosaminoglycans are
particularly preferred for use
herein.
As an example, chondroitin provides the structure and allows various molecules
to
transport through cartilage (which is important, since there is no blood
supply to cartilage).
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Chondroitin is a major constituent of cartilage and contains repeating chains
of
mucopolysaccharides.
Typical single dosing of the glycosaminoglycans is preferably from about 1 mg
to about
grams, more preferably from about 100 mg to about 5 grams, even more
preferably from about
150 mg to about 1000 mg, and most preferably from about 250 mg to about 800
mg, based on
the molecular weight of chondroitin. All other glycosaminoglycans may be
similarly dosed, based
on the molecular weight of chondroitin. Typically, the composition comprising
the
glycosaminoglycan is dosed from about once to about five times daily,
preferably from about once
to about three times daily, most preferably once daily.
Methylsulfonylmethane and Precursors of Methylsulfonylmethane
The chondroprotective agent herein may also be methylsufonylmethane, or a
precursor
thereof. As used herein, the term "precursor thereof' means a compound which,
in mammalian
systems, is converted to methylsulfonylmethane in vivo. Methylsulfonylmethane,
and precursors
thereof, are common ingredients found in vivo and in nature, e.g., in
unprocessed foods. Without
intending to be limited by theory, it is believed that the sulfur moiety
present in
methylsulfonylmethane, and its precursors, provides the disulfide bridging
(also commonly known
as "tie-bars" or "cross-links") necessary to hold the connective tissue in
joints together.
While unprocessed foods contain methylsulfonylmethane, and the precursors
thereof,
conventional food processing and preparation causes the loss of these
compounds from the
foods. Therefore, commonly ingested foods may become deficient in these
compounds. In these
respects, methylsulfonylmethane is similar to vitamins and minerals which are
typically partially or
totally lost during normal food processing and preparation. It is therefore an
important
embodiment of this invention to include methylsulfonylmethane or a precursor
thereof in the
present compositions.
Non-limiting examples of precursors of methylsulfonylmethane include
methionine and
methyl sulfide. See e.a., Herschler et al., U.S. Patent No. 4,863,748, issued
September 5, 1989.
Precursors of methylsulfonylmethane are associated with a variety of health
benefits, including
joint benefits (such as relief from osteoarthritis and rheumatoid arthritis),
as well as anti-
inflammation.
In accordance with the present invention, wherein methanesulfonylmethane is
included
within a present composition, a single dose of methanesulfonylmethane within
the composition is
preferably from about 0.01 mg to about 2000 mg, more preferably from about
0.01 mg to about
500 mg, even more preferably from about 1 mg to about 200 mg, and most
preferably from about
1 mg to about 100 mg. The precursors of methanesulfonylmethane may be
similarly dosed,
based on the molecular weights of the precursors relative to
methanesulfonylmethane. Typically,
the composition comprising methylsulfonyl methane, or a precursor thereof, is
dosed from about
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once to about five times daily, preferably from about once to about three
times daily, most
preferably once daily.
S-Adenosylmethionine
S-adenosylmethionine, which is commonly known as SAM-e, is a compound which is
found in most, if not all, living cells. Without intending to be limited by
theory, SAM-a is produced
through reaction of the essential amino acid methionine and the energy
molecule known as
adenosine triphosphate (commonly known as ATP). SAM-a manufactures the
components of
cartilage and repairs, restores, and maintains joint function. SAM-a is made
in vivo from the
amino acid methionine, and is found in ordinary dietary sources such as meats,
soybeans, eggs,
seeds, and lentils.
In accordance with the present invention, wherein SAM-a is included within a
present
composition, a single dose of SAM-a within the composition is preferably from
about 1 mg to
about 2000 mg, more preferably from about 100 mg to about 700 mg, even more
preferably from
about 150 mg to about 600 mg, and most preferably from about 200 mg to about
400 mg.
Typically, the composition comprising SAM-a is dosed from about once to about
five times daily,
preferably from about once to about three times daily, most preferably once
daily.
B. Water
Water is the second necessary constituent of the present compositions. The
present
inventors have surprisingly discovered that bioavailability and efficacy of
aqueous
chondroprotective compositions is significantly greater relative to that of
dry forms of
chondroprotective compositions (e.g., tablets or capsules), even wherein each
of these
compositions is ingested within about 4 hours of ingestion of a food or
beverage. Accordingly,
efficacy of chondroprotective compositions is surprisingly related to behavior
of the consumer in
need of treatment, in particular, the relationship between 1 ) ingestion of a
particular form of
chondroprotective composition; and 2) food or beverage intake. It has
therefore been found that
aqueous chondroprotective compositions are surprisingly more effective
relative to the
corresponding dry-forms (i.e., those containing less than about 2% water).
The present compositions comprise from about 80% to about 99.9999% water.
Preferably, the compositions preferably comprise at least about 82% water,
more preferably at
least about 83% water, still more preferably at least about 84% water, even
more preferably at
least about 85% water, and most preferably at least about 86% water. The water
included at
these levels includes all added water and any water present in combination
components, for
example, fruit juice.
C. Particularly Preferred Elements of the Present Compositions
The compositions of this invention preferably exhibit a pH of from about 2 to
about 7,
more preferably from about 2 to about 5, still more preferably from about 3 to
about 5, even more
preferably from about 3.5 to about 4.5, and most preferably from about 3.7 to
about 4.2..
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If necessary, the present compositions may comprise one or more acidulants in
order to
reach, and maintain, the presently preferred pH. Composition acidity can be
adjusted to and
maintained within the requisite range by known and conventional methods, e.g.,
the use of one or
more acidulants.
Organic as well as inorganic edible acids may be used to adjust the pH of the
ready-to-
drink beverage compositions. The acids can be present in their undissociated
form or,
alternatively, as their respective salts, for example, potassium or sodium
hydrogen phosphate,
potassium or sodium dihydrogen phosphate salts. The preferred acids are edible
organic acids
which include citric acid, malic acid, fumaric acid, adipic acid, phosphoric
acid, gluconic acid,
tartaric acid, ascorbic acid, acetic acid, phosphoric acid or mixtures
thereof. The most preferred
acids are citric and malic acids.
D. Other Optional Components of the Present Compositions
The compositions herein are typically beverage compositions, beverage
concentrates,
foods or supplements (including, for example, dietary supplements, over-the-
counter remedies,
and pharmaceutical remedies). The compositions herein may comprise additional
optional
components to enhance, for example, their performance in providing joint
health, bone health,
other health benefits, a desirable nutritional profile, and / or organoleptic
properties. For example,
one or more omega-3-fatty acids, bracers, flavanols, milk base solids, soluble
fibers, non-caloric
sweeteners, nutrients, flavoring agents, coloring agents, preservatives,
emulsifiers, oils,
carbonation components, and the like may be included in the compositions
herein. Such optional
components may be dispersed, solubilized, or otherwise mixed into the present
compositions.
These components may be added to the compositions herein provided they do not
substantially
hinder the properties of the beverage composition, particularly the provision
of joint and / or bone
health. Non-limiting examples of optional components suitable for use herein
are given below.
Omega-3-Fatty Acids
In a particularly preferred embodiment of the present invention, one or more
omega-3-
fatty acids may be added to the present compositions. Omega-3-fatty acids are
anti-inflammatory
compounds which act as competitive inhibitors of the arachidonic acid cascade.
The omega-3-
fatty acids are precursors to the synthesis of prostaglandins which function
in mammals to
regulate inflammation. See e.g., Burger, U.S. Patent No. 5,843,919, issued
December 1, 1998.
The omega-3-fatty acid optionally utilized herein may be any omega-3-fatty
acid or
combination of omega-3-fatty acids. Non-limiting examples of omega-3-fatty
acids which are
suitable for use herein include eicosapentaenoic acid (also known as EPA),
docosahexaenoic
acid (also known as DHA), and mixtures thereof.
Optionally, the omega-3-fatty acid, as well as all other oil soluble
components described
herein, can be added to the present compositions via an emulsion and / or
encapsulation.
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Additionally, in essentially dry compositions, the omega-3-fatty acid may be
spray dried according
to commonly known techniques.
Wherein one or more omega-3-fatty acids is utilized in the present
compositions, the ratio
of the chondroprotective agent herein and the omega-3-fatty acids is often
important for
optimization of health benefits, particularly joint health benefits, bone
health benefits, and anti-
inflammatiori. Preferably, the ratio of the chondroprotective agent to the
total omega-3-fatty
acids) present in the composition (on a weight to weight basis) is from about
95:5 to about 5:95,
more preferably from about 75:25 to about 25:75, most preferably from about
60:40 to about
40:60. The dosage of omega-3-fatty acids) included in the composition is
therefore preferably
administered according to these guidelines. Typically dosage levels of the
chondroprotective
agent has been detailed herein above.
Bracers
As is commonly known in the art, bracers can be obtained by extraction from a
natural
source or can be synthetically produced. Non-limiting examples of bracers
include
methylxanthines, e.g., caffeine, theobromine, and theophylline. Additionally,
numerous other
xanthine derivatives have been isolated or synthesized, which may be utilized
as a bracer in the
compositions herein. See e.a., Bruns, Biochemical Pharmacology, Vol. 30, pp.
325 - 333 (1981 )
which, describes, inter alia, xanthine, 9-methyl xanthine, 7-methyl xanthine,
3-methyl xanthine,
3,7-dimethyl xanthine, 8-chloromethyf-3,7-dimethyl xanthine, 8-hydroxymethyl-
3,7-dimethyl
xanthine, 3,7-diethyl xanthine, 3,7-bis-(2-hydroxyethyl) xanthine, 3-propyl-7-
(dimethylaminoethyl)
xanthine, 1-methyl xanthine, 1,9-dimethyl xanthine, 1-methyl-8-methylthio
xanthine, 8-phenyl-1-
methyl xanthine, 1,7-dimethyl xanthine, 1,7-dimethyl-8-oxo xanthine, 1,3-
dimethyl xanthine, 1,3,9-
trimethyl xanthine, 8-fluoro theophylline, 8-chloro theophylline, 8-bromo
theophylline, 8-thio
theophylline, 8-methylthio theophylline, 8-ethylthio theophylline, 8-nitro
theophylline, 8-
methylamino theophylline, 8-dimethylamino theophyllirie, 8-methyl
theophylline, 8-ethyl
theophylline, 8-propyl theophylline, 8-cyclopropyl theophylline, theophylline-
8-propionate (ethyl
ester), 8-benzyl theophyfline, 8-cyclopentyl theophylline, 8-cyclohexyl
theophylline, 8-(3-indolyl)
theophylline, 8-phenyl theophylline, 9-methyl-8-phenyl theophylline, 8-(p-
chlorophenyl)
theophylline, 8-(p-bromophenyl) theophylline, 8-(p-methoxyphenyl)
theophylline, 8-(p-nitrophenyl)
theophylline, 8-(p-dimethylaminophenyl) theophylline, 8-(p-methylphenyl)
theophylline, 8-(3,4-
dichlorophenyl) theophylline, 8-(m-nitrophenyl) theophylline, 8-(o-
nitrophenyl) theophylline, 8-(0-
carboxyphenyl) theophylline, 8-(1-naphthyl) theophylline, 8-(2,6-dimethyl-4-
hydroxyphenyl)
theophylline, 7-methoxy-8-phenyl theophylline, 1,3,7-trimethyl xanthine, S-
chloro caffeine, S-oxo
caffeine, S-methoxy caffeine, S-methylamino cafFeine, 8-diethylamino cafFeine,
8-ethyl caffeine, 7-
ethyl theophylline, 7-(2-chloroethyl) theophylline, 7-(2-hydroxyethyl)
theophylline, 7-
(carboxymethyl) theophylline, 7-(carboxymethyl) theophylline (ethyl ester), 7-
(2-hydroxypropyl)
theophylline, 7-(2,3-dihydroxypropyl) theophylline, 7-b-D-ribofuranosyl
theophylline, 7-(glycero-
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pent-2-enopyranosyl) theophylline, 7-phenyl theophylline, 7,8-diphenyl
theophylline, 1-methyl-3,7-
diethyl xanthine, 1-methyl-3-isobutyl xanthine, 1-ethyl-3,7-dimethyl xanthine,
1,3-diethyl xanthine,
1,3,7-triethyl xanthine, 1-ethyl-3-propyl-7-butyl-8-methyl xanthine, 1,3-
dipropyl xanthine, 1,3-diallyl
xanthine, 1-butyl-3,7-dimethyl xanthine, 1-hexyl-3,7-dimethyl xanthine, and 1-
(5-oxohexyl)-3,7-
dimethyl xanthine.
Additionally, one or more of these bracers are present in, for example,
coffee, tea, kola
nut, cacao pod, mate', yaupon, guarana paste, and yoco. Natural plant extracts
are the preferred
sources of bracers as they may contain other compounds that delay the
bioavailability of the
bracer thus they may provide mental refreshment and alertness without tension
or nervousness.
The most preferred methylxanthine is caffeine. Caffeine may be obtained from
the
aforementioned plants and their waste or, alternatively, may be synthetically
prepared. Preferred
botanical sources of caffeine which may be utilized as a complete or partial
source of caffeine
include green tea, guarana, mate', black tea, cola nuts, cocoa, and coffee. As
used herein, green
tea, guarana, coffee, and mate' are the most preferred botanical sources of
caffeine, most
preferably green tea, guarana, and coffee. Mate' may have the additional
benefit of an appetite
suppressing effect and may be included for this purpose as well. The total
amount of caffeine, in
any embodiment of the present invention, includes the amount of caffeine
naturally present in the
tea extract, flavoring agent, botanical and any other components, as well as
any added caffeine.
Any bracer utilized herein is preferably present in physiologically relevant
amounts, which
means that the sources used in the practice of this invention provide a safe
and effective quantity
to achieve the desired mental alertness.
Wherein a bracer is utilized in the present compositions, such compositions
will
preferably comprise from about 0.0005°l° to about 1 %, more
preferably from about 0.003% to
about 0.5%, still more preferably from about 0.003% to about 0.2%, even more
preferably from
about 0.005% to about 0.05%, and most preferably from about 0.005% to about
0.02% of a
bracer, by weight of the composition. Of course, as the skilled artisan will
comprehend, the actual
amount of bracer added will depend its biological effect, for example, effect
of mental alertness on
the consumer.
In all of the present compositions, the total amount of bracer includes any
added bracer
as well as any bracer naturally present in any other component of the present
invention.
Flavanols
Flavanols are natural substances present in a variety of plants (e.g., fruits,
vegetables,
and flowers). The flavanols which may be utilized in the present invention can
be extracted from,
for example, fruit, vegetables, green tea or other natural sources by any
suitable method well
known to those skilled in the art. For example, extraction with ethyl acetate
or chlorinated organic
solvents is a common method to isolate flavanols from green tea. Flavanols may
be extracted
from either a single plant or mixtures of plants. Many fruits, vegetables, and
flowers contain
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flavanols but to a lesser degree relative to green tea. Plants containing
flavanols are known to
those skilled in the art. Examples of the most common flavanols which are
extracted from tea
plants and other members of the Catechu gambir (Uncaria family) include, for
example, catechin,
epicatechin, gallocatechin, epigallocatechin, epicatechin gallate, and
epigallocatechin gallate.
The flavanols utilized in all compositions of the present invention can be in
the form of a
tea extract. The tea extract can be obtained from the extraction of
unfermented teas, fermented
teas, partially fermented teas, and mixtures thereof. Preferably, the tea
extracts are obtained
from the extraction of unfermented and partially fermented teas. The most
preferred tea extracts
are obtained from green tea. Both hot and cold extracts can be used in the
present invention.
Suitable methods for obtaining tea extracts are well known. See e.a.,
Ekanayake, U.S. Patent No.
5,879,733, issued March 9, 1999; Tsai, U.S. Patent No. 4,935,256, issued June,
1990; Lunder,
U.S. 4,680,193, issued July, 1987; and Creswick, U.S. Patent No. 4,668,525,
issued May 26,
1987.
The preferred source of flavanols in the compositions of the present invention
is green
tea. Wherein green tea, and in particular the flavanols present in green tea,
are incorporated into
the beverage, the present inventors have discovered that the flavanols are at
least partially
responsible for delaying the bioavailability of bracers, which contributes to
the reduction and / or
elimination of nervousness and tension typically associated with such bracers.
Alternatively, these same flavanols may be prepared by synthetic or other
appropriate
chemical methods and incorporated into the present compositions. Flavanols,
including catechin,
epicatechin, and their derivatives are commercially available.
The amount of flavanols in the compositions of the present invention can vary.
However,
wherein one or more flavanols are utilized, preferably from about 0.001 % to
about 5%, more
preferably from about 0.001 % to about 2%, even more preferably from about
0.01 % to about 1 %,
and most preferably from about 0.01 % to about 0.05% of one or more flavanols
is utilized, by
weight of the composition.
In all of the embodiments of the present invention, the total amount of
flavanols includes
any added flavanols as well as any flavanols naturally present in any other
component of the
present invention.
Milk Base Solids
One or more milk base solids may also optionally be included in the
compositions of the
present invention. As used herein, milk base means milk from one or more
mammals or a plant-
derived milk, and includes, for example, fermented milk, lactic acid beverages
obtained by lactic
acid fermentation or otherwise acidified, sterilized milk base, liquid milk,
and milk products such
as skim milk powder or whole milk powder or other powdered forms of milk. As
used herein, milk
base solids means the solids content or dry matter of milk base.
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Wherein one or more milk base solids is utilized, the desired total level of
milk base
solids, calculated on a milk solids basis for the compositions of the present
invention, is from
about 0.001 % to about 15%, preferably from about 0.005% to about 10%, and
most preferably
from about 0.1 % to about 5%. The total amount of milk base solids includes
any added milk base
solid as well as any milk base solid naturally present, in any other component
of the present
invention.
Soluble Fibers
One or more soluble fibers may also optionally be included in the compositions
of the
present invention to provide, for example, nutritive benefits. Soluble fibers
which can be used
singularly or in combination in all embodiments of the present invention
include but are not limited
to pectins, psyllium, guar gum, xanthan gum, alginates, gum arabic, fructo-
oligosaccharides,
inulin, agar, and carrageenan. Preferred among these soluble fibers are at
least one of guar
gum, xanthan, and carrageenan, most preferably at least one of guar gum and
xanthan. These
soluble fibers may also serve as stabilizing agents in the various embodiments
of this invention.
Particularly preferred soluble fibers for use herein are glucose polymers,
preferably those
which have branched chains. Preferred among these soluble fibers is one
marketed under the
trade name Fibersol2, commercially available from Matsutani Chemical Industry
Co., Itami City,
Hyogo, Japan.
Pectin and fructo-oligosaccharides are also preferred soluble fibers herein.
Even more
preferably, pectin and fructo-oligosaccharides are used in combination. The
preferred ratio of
pectin to fructo-oligosaccharide is from about 3:1 to about 1:3, by weight of
the composition. The
preferred pectins have a degree of esterification higher than about 65%.
The preferred fructo-oligosaccharides are a mixture of fructo-oligosaccharides
composed
of a chain of fructose molecules linked to a molecule of sucrose. Most
preferably, they have a
nystose to kestose to fructosyl-nystose ratio of about 40:50:10, by weight of
the composition.
Preferred fructo-oligosaccharides may be obtained by enzymatic action of
fructosyltransferase on
sucrose such as those which are, for example, commercially available from
Beghin-Meiji
Industries, Neuilly-sur-Seine, France.
Preferred pectins are obtained by hot acidic extraction from citrus peels and
may be
obtained, for example, from Danisco Co., Braband, Denmark.
Wherein a soluble fiber is utilized, the desired total level of soluble
dietary fiber for the
compositions of the present invention is from about 0.01 % to about 15%,
preferably from about
0.1 % to about 5%, more preferably from about 0.1 % to about 3%, and most
preferably from about
0.2% to about 2%, by weight of the composition. The total amount of soluble
.dietary fiber
includes any added soluble dietary fiber as well as any soluble dietary fiber
naturally present in
any other component of the present invention.
Sweeteners
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The compositions of the present invention can, and typically will, contain an
effective
amount of one or more sweeteners, including carbohydrate sweeteners and
natural and/or
artificial no/low calorie sweeteners. The amount of the sweetener used in the
beverages of the
present invention typically depends upon the particular sweetener used and the
sweetness
intensity desired. For no/low calorie sweeteners, this amount varies depending
upon the
sweetness intensity of the particular sweetener.
The compositions of the present invention can be sweetened with any of the
carbohydrate sweeteners, preferably monosaccharides and l or disaccharides.
Sweetened
beverages will typically comprise from about 0.1 % to about 20%, most
preferably from about 6 to
about 14%, sweetener. These sugars can be incorporated into the beverages in
solid or liquid
form but are typically, and preferably, incorporated as a syrup, most
preferably as a concentrated
syrup such as high fructose corn syrup. For purposes of preparing beverages of
the present
invention, these sugar sweeteners can be provided to some extent by other
components of the
beverage such as, for example, the fruit juice component and / or flavors.
Preferred sugar sweeteners for use in beverage products of the present
invention are
sucrose, fructose, glucose, and mixtures thereof, particularly sucrose and
fructose. Fructose can
be obtained or provided as liquid fructose, high fructose corn syrup, dry
fructose or fructose
syrup, but is preferably provided as high fructose corn syrup. High fructose
corn syrup (HFCS) is
commercially available as HFCS-42, HFCS-55 and HFCS-90, which comprise 42%,
55% and
90%, respectively, by weight of the sugar solids therein, as fructose. Other
naturally occurring
sweeteners or their purified extracts, such as glycyrrhizin, stevioside, the
protein sweetener
thaumatin, the juice of Luo Han Guo (containing the sweet mogrosides)
disclosed in, for example,
Fischer et al., U. S. Patent No. 5,433,965, issued July 18, 1995, and the like
can also be used in
the beverages of the present invention.
Effective levels of non-caloric sweeteners may optionally be used in the
compositions of
the present invention to further sweeten such compositions. Non-limiting
examples of non-caloric
sweeteners include aspartame, saccharine, cyclamates, acesulfame K, L-aspartyl-
L-
phenylalanine lower alkyl ester sweeteners, L-aspartyl-D-alanine amides such
as, for example,
those disclosed in Brennan et al., U.S. Patent No. 4,411,925, issued 1983, L-
aspartyl-D-serine
amides such as, for example, those disclosed in Brennan et al., U.S. Patent
No. 4,399,163,
issued 1983, L-aspartyl-hydroxymethyl alkane amide sweeteners such as, for
example, those
disclosed in Brand, U.S. Patent No. 4,338,346, issued 1982, L-aspartyl-1-
hydroxyethylalkane
amide sweeteners such as, for example, those disclosed in Rizzi, U.S. Patent
No. 4,423,029,
issued 1983, glycyrrhizins, and synthetic alkoxy aromatics. Aspartame and
acesulfame-K are the
most preferred non-caloric sweeteners utilized herein, and may be utilized
alone or in
combination.
CA 02408611 2002-11-05
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Wherein one or more sweeteners are utilized herein, the total non-caloric
sweetener is
preferably utilized at levels from about 0.0001 % to about 5%, more preferably
from about 0.001
to about 3%, still more preferably from about 0.005% to about 2%, even more
preferably from
about 0.01 % to about 1 %, and most preferably from about 0.01 % to about
0.05%, by weight of
the composition.
Nutrients
The compositions herein may optionally, but preferably, be fortified further
with one or
more nutrients, especially one or more vitamins and / or minerals. The U.S.
Recommended Daily
Intake (USRDI) for vitamins and minerals are defined and set forth in the
Recommended Daily
Dietary Allowance-Food and Nutrition Board, National Academy of Sciences-
National Research
Council.
Unless otherwise specified herein, wherein a given mineral is present in the
composition,
the composition typically comprises at least about 1 %, preferably at least
about 5%, more
preferably from about 10% to about 200%, even more preferably from about 40%
to about 150%,
and most preferably from about 60% to about 125% of the USRDI of such mineral.
Unless
otherwise specified herein, wherein a given mineral is present in the
composition, the composition
comprises at least about 1 %, preferably at least about 5%, more preferably
from about 10% to
about 200%, even more preferably from about 20% to about 150%, and most
preferably from
about 25% to about 120% of the USRDI of such vitamin.
Non-limiting examples of such further vitamins and minerals, include niacin,
thiamin, folic
acid, pantothenic acid, biotin, vitamin A, vitamin C, vitamin B2, vitamin B3,
vitamin B6, vitamin B~2,
vitamin D, vitamin E, vitamin K, iron, zinc, copper, phosphorous, iodine,
chromium, molybdenum,
and fluoride. Preferably, wherein a further vitamin or mineral is utilized the
vitamin or mineral is
selected from niacin, thiamin, folic acid, iodine, vitamin A, vitamin C,
vitamin B6, vitamin B12
vitamin D, vitamin E, iron, zinc, and calcium. Preferably, at least one
vitamin is selected from
vitamin C, vitamin B6, vitamin Biz, vitamin E, pantothenic acid, niacin, and
biotin. Also preferably,
the composition comprises vitamin C and one or more other vitamins selected
from vitamin B6,
vitamin B~2, vitamin E, pantothenic acid, niacin, and biotin.
Commercially available vitamin A sources may also be included in the present
compositions. As used herein, "vitamin A" includes, but is not limited to,
vitamin A (retinol), ~i-
carotene, retinol palmitate, and retinol acetate. The vitamin A may be in any
form, for example,
an oil, beadlets, or encapsulated. Wherein vitamin A is present in the
compositions herein, the
product comprises at least about 1 %, preferably at least about 5%, more
preferably from about
10% to about 200%, even more preferably from about 15% to about 150%, and most
preferably
from about 20% to about 120% of the USRDI of such vitamin. Wherein vitamin A
is present in the
compositions herein, it is especially preferred to include about 25% of the
USRDI of vitamin A.
The quantity of vitamin A to be added is dependent on processing conditions
and the amount of
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vitamin A deliver desired after storage. Preferably, wherein vitamin A is
included within the
present compositions, the compositions comprise from about 0.0001 % to about
0.2%, more
preferably from about 0.0002% to about 0.12%, also preferably from about
0.0003% to about
0.1 %, even more preferably from about 0.0005% to about 0.08%, and most
preferably from about
0.001 % to about 0.06% of vitamin A, by weight of the product.
Commercially available sources of vitamin B2 (also known as riboflavin) may be
utilized
in the present compositions. Wherein vitamin B2 is present in the compositions
herein, the
product comprises at least about 1 %, preferably at least about 5%, more
preferably from about
5% to about 200%, even more preferably from about 10% to about 150%, and most
preferably
from about 10% to about 120% of the USRDI of such vitamin. Wherein vitamin B2
is present in
the compositions herein, it is especially preferred to include from about 15%
to about 35% of the
USRDI of vitamin B2.
Vitamin C (ascorbic acid) is a particularly preferred optional ingredient for
use herein.
Without intending to be limited by theory, it is believed that vitamin C may
be utilized to enhance
the benefits herein, by serving as a co-factor for the enzyme which cross-
links collagen.
Encapsulated ascorbic acid and edible salts of ascorbic acid can also be used.
Wherein
vitamin C is present in the compositions herein, the product comprises at
least about 1 %,
preferably at least about 5%, more preferably from about 10% to about 200%,
even more
preferably from about 20% to about 150%, and most preferably from about 25% to
about 120% of
the USRDI of such vitamin. Wherein vitamin C is present in the compositions
herein, it is
especially preferred to include about 100% of the USRDI of vitamin C. The
quantity of vitamin C
to be added is dependent on processing conditions and the amount of vitamin C
deliver desired
after storage. Preferably, wherein vitamin C is included within the present
compositions, the
compositions comprise from about 0.005% to about 0.2%, more preferably from
about 0.01 % to
about 0.12%, also preferably from about 0.02% to about 0.1 %, even more
preferably from about
0.02% to about 0.08%, and most preferably from .about 0.03% to about 0.06% of
vitamin C, by
weight of the product.
Nutrifiionally supplemental amounts of other vitamins which may be
incorporated herein
include, but are not limited to, vitamins B6 and B12, folic acid, niacin,
pantothenic acid, folic acid,
vitamin D, and vitamin E. Wherein the product comprises one of these vitamins,
the product
preferably comprises at least 5%, preferably at least 25%, and most preferably
at least 35% of the
USRDI for such vitamin.
Minerals which may optionally be included in the compositions herein are, for
example,
calcium, manganese, magnesium, boron, zinc, iodine, iron, and copper. Minerals
may be, for
example, salts, chelated, complexed, or in colloidal form.
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Any soluble salt of these minerals suitable for inclusion edible compositions
can be used,
for example, magnesium citrate, magnesium gluconate, magnesium sulfate, zinc
chloride, zinc
sulfate, potassium iodide, copper sulfate, copper gluconate, and copper
citrate.
Manganese is a particularly preferred mineral for use herein, as this mineral
is involved in
the synthesis of glycosaminoglycans, collagen, and glycoproteins. Additionally
manganese
deficiencies can lead to abnormal bone growth, inflamed joints, bone loss, and
arthritis.
Manganese ascorbate is a particularly preferred form of manganese for use
herein. Typical
manganese dosages range from about 0 mg to about 1000 mg, more preferably from
about 50
mg to about 950 mg, and most preferably from about 50 mg to about 250 mg for a
human or large
mammal (e.g., horse).
Boron is a particularly preferred mineral for use herein, as this mineral is
necessary for
osteocalcin formation in bone.
Calcium is a particularly preferred mineral for use in the present invention.
Preferred
sources of calcium include, for example, amino acid chelated calcium, calcium
carbonate, calcium
oxide, calcium hydroxide, calcium sulfate, calcium chloride, calcium
phosphate, calcium hydrogen
phosphate, calcium dihydrogen phosphate, calcium citrate, calcium malate,
calcium titrate,
calcium gluconate, calcium realate, calcium tantrate, and calcium lactate, and
in particular
calcium citrate-malate. The form of calcium citrate-malate is described in,
e.g., Mehansho et al.,
U.S. Patent No. 5,670,344, issued September 23, 1997; Diehl et al., U.S..
Patent No. 5,612,026,
issued March 18, 1997; Andon et al., U.S. Patent No. 5,571,441, issued
November 5, 1996;
Meyer et al., U.S. Patent No. 5,474,793, issued December 12, 1995; Andon et
al., U.S. Patent
No. 5,468,506, issued November 21, 1995; Burkes et al., U.S. Patent No.
5,445,837, issued
August 29, 1995; Dake et al., U.S. Patent No. 5,424,082, issued June 13, 1995;
Burkes et al.,
U.S. Patent No. 5,422,128, issued June 6, 1995; Burkes et al., U.S. Patent No.
5,401,524, issued
March 28, 1995; Zunigia et al., U.S. Patent No. 5,389,387, issued February 14,
1995; Jacobs,
U.S. Patent No. 5,314,919, issued May 24, 1994; Saltman et al., U.S. Patent
No. 5,232,709,
issued August 3, 1993; Camden et al., U.S. Patent No. 5,225,221, issued July
6, 1993; Fox et al.,
U.S. Patent No. 5,215,769, issued June 1, 1993; Fox et al., U.S. Patent No.
5,186,965, issued
February 16, 1993; Saltman et al., U.S. Patent No. 5,151,274, issued September
29, 1992;
Kochanowski, U.S. Patent No. 5,128,374, issued July 7, 1992; Mehansho et al.,
U.S. Patent No.
5,118,513, issued June 2, 1992; Andon et al., U.S. Patent No. 5,108,761,
issued April 28, 1992;
Mehansho et al., U.S. Patent No. 4,994,283, issued February 19, 1991; Nakel et
al., U.S. Patent
No. 4,786,510, issued November 22, 1988; and Nakel et al., U.S. Patent No.
4,737,375, issued
April 12, 1988. Preferred compositions of the present invention will comprise
from about 0.01 % to
about 0.5%, more preferably from about 0.03% to about 0.2%, even more
preferably from about
0.05% to about 0.15%, and most preferably from about 0.1 % to about 0.15% of
calcium, by
weight of the product.
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iron may also be utilized in the compositions and methods of the present
invention.
Acceptable forms of iron are well-known in the art. The amount of iron
compound incorporated
into the product will vary widely depending upon the level of supplementation
desired in the final
product and the targeted consumer. Iron fortified compositions of the present
invention typically
contain from about 5% to about 100%, preferably from about 15% to about 50%,
and most
preferably about 20% to about 40% of the USRDI for iron.
Ferrous iron is typically better utilized by the body than ferric iron. Highly
bioavailable
ferrous salts that can be used in the ingestible compositions of the present
invention are ferrous
sulfate, ferrous fumarate, ferrous succinate, ferrous gluconate, ferrous
lactate, ferrous tartarate,
ferrous citrate, ferrous amino acid chelates, as well as mixtures of these
ferrous salts. While
ferrous iron is typically more bioavailable, certain ferric salts can also
provide highly bioavailable
sources of iron. Highly bioavailable ferric salts that can be used in the food
or beverage
compositions of the present invention are ferric saccharate, ferric ammonium
citrate, ferric citrate,
ferric sulfate, as well as mixtures of these ferric salts. Combinations or
mixtures of highly
bioavailable ferrous and ferric salts can be used in these edible mixes and
ready-to-serve
beverages. The preferred sources of highly bioavailable iron are ferrous
fumarate and ferrous
amino acid chelates.
Ferrous amino acid chelates particularly suitable as highly bioavailable iron
sources for
use in the present invention are those having a ligand to metal ratio of at
least 2:1. For example,
suitable ferrous amino acid chelates having a ligand to metal mole ratio of
two are those of
formula:
Fe(L)2
where L is an alpha amino acid, dipeptide, tripeptide, or quadrapeptide
ligand. Thus, L can be
any ligand which is a naturally occurring alpha amino acid selected from
alanine, arginine,
asparagine, aspartic acid, cysteine, cystine, glutamine, glutamic acid,
glycine, histidine,
hydroxyproline, isoleucine, leucine, lysine, methionine, ornithine,
phenylalanine, proline, serine,
threonine, tryptophan, tyrosine, and valine; or dipeptides, tripeptides, or
quadrapeptides formed
by any combination of these alpha amino acids. See e.a., Ashmead et al., U.S.
Patent No.
4,863,898, issued September 5, 1989; Ashmead, U.S. Patent No. 4,830,716,
issued May 16,
1989; and Ashmead, U.S. Patent No. 4,599,152, issued July 8, 1986, all of
which are
incorporated by reference. Particularly preferred ferrous amino acid chelates
are those where the
reacting ligands are glycine, lysine, and leucine. Most preferred is the
ferrous amino acid chelate
sold under the mark Ferrochel° (Albion Laboratories, Salt Lake City,
Utah) wherein the ligand is
glycine.
In addition to these highly bioavailable ferrous and ferric salts, other
sources of
bioavailable iron can be included in the food and beverage compositions of the
present invention.
Other sources of iron particularly suitable for fortifying compositions of the
present invention
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included certain iron-sugar-carboxylate complexes. In these iron-sugar-
carboxylate complexes,
the carboxylate provides the counterion for the ferrous (preferred) or ferric
iron: The overall
synthesis of these iron-sugar-carboxylate complexes involves the formation of
a calcium-sugar
moiety in aqueous media (for example, by reacting calcium hydroxide with a
sugar, reacting the
iron source (such as ferrous ammonium sulfate) with the calcium-sugar moiety
in aqueous media
to provide an iron-sugar moiety, and neutralizing the reaction system with a
carboxylic acid (the
"carboxylate counterion") to provide the desired iron-sugar- carboxylate
complex. Sugars that
can be used to prepare the calcium-sugar moiety include any of the ingestible
saccharidic
materials, and mixtures thereof, such as glucose, sucrose and fructose,
mannose, galactose,
lactose, maltose, and the like, with sucrose and fructose being the more
preferred. The
carboxylic acid providing the "carboxylate counterion" can be any ingestible
carboxylic acid such
as citric acid, mafic acid tartaric acid, tactic acid, succinic acid,
propionic acid, etc., as well as
mixtures of these acids.
These iron-sugar-carboxylate complexes can be prepared in the manner described
in,
e.g., Nakel et al., U.S. Patent Nos. 4,786,510 and 4,786,518, issued November
22, 1988, both of
which are incorporated by reference. These materials are referred to as
"complexes", but they
may exist in solution as complicated, highly hydrated, protected colloids; the
term "'complex" is
used for the purpose of simplicity.
Zinc may also be utilized in the compositions and methods of the present
invention.
Acceptable forms of zinc are well-known in the art. Zinc fortified
compositions of the present
invention typically contain from about 5% to about 100%, preferably from about
15% to about
50%, and most preferably about 25% to about 45% of the USRDI for zinc. The
zinc compounds
which can be used in the present invention can be in any of the commonly used
forms such as,
e.g., zinc sulfate, zinc chloride, zinc acetate, zinc gluconate, zinc
ascorbate, zinc citrate, zinc
aspartate, zinc picolinate, amino acid chelated zinc, and zinc oxide. Zinc
gluconate and amino
acid chelated zinc are particularly preferred.
Flavoring Agents
One or more flavoring agents are recommended for the embodiments of the
present
invention in order to enhance their palatability. Any natural or synthetic
flavor agent can be used
in the present invention. For example, one or more botanical and / or fruit
flavors may be utilized
herein. As used herein, such flavors may be synthetic or natural flavors.
Particularly preferred fruit flavors are exotic and lactonic flavors such as,
for example,
passion fruit flavors, mango flavors, pineapple flavors, cupuacu flavors,
guava flavors, cocoa
flavors, papaya flavors, peach flavors, and apricot flavors. Besides these
flavors, a variety of
other fruit flavors can be utilized such as, for example, apple flavors,
citrus flavors, grape flavors,
raspberry flavors, cranberry flavors, cherry flavors, grapefruit flavors, and
the like. These fruit
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flavors can be derived from natural sources such as fruit juices and flavor
oils, or may
alternatively be synthetically prepared.
Preferred botanical flavors include, for example, tea (preferably black and
green tea,
most preferably green tea), aloe vera, guarana, ginseng, ginkgo, hawthorn,
hibiscus, rose hips,
chamomile, peppermint, fennel, ginger, licorice, lotus seed, schizandra, saw
palmetto,
sarsaparilla, safflower, St. John's Wort, ,curcuma, cardimom, nutmeg, cassia
bark, buchu,
cinnamon, jasmine, haw, chrysanthemum, water chestnut, sugar cane, lychee,
bamboo shoots,
vanilla, coffee, and the like. Preferred among these is tea, guarana, ginseng,
ginko, and coffee.
In particular, the combination of tea flavors, preferably green tea or black
tea flavors (preferably
green tea), optionally together with fruit flavors has an appealing taste. In
another preferred
embodiment, coffee is included within the present compositions. A combination
of green tea and
cofFee in the present compositions is often preferred.
The flavor agent can also comprise a blend of various flavors. If desired, the
flavor in the
flavoring agent may be formed into emulsion droplets which are then dispersed
in the beverage
composition or concentrate. Because these droplets usually have a specific
gravity less than that
of water and would therefore form a separate phase, weighting agents (which
can also act as
clouding agents) can be used to keep the emulsion droplets dispersed in the
beverage
composition or concentrate. Examples of such weighting agents are brominated
vegetable oils
(BVO) and resin esters, in particular the ester gums. See L.F. Green,
Developments in Soft
Drinks Technology, Vol: 1, Applied Science Publishers Ltd., pp. 87-93 (1978)
for a further
description of the use of weighting and clouding agents in liquid beverages.
Typically the
flavoring agents are conventionally available as concentrates or extracts or
in the form of
synthetically produced flavoring esters, alcohols, aldehydes, terpenes,
sesquiterpenes, and the
like.
Coloring Aqent
Small amounts of one or more coloring agents may be utilized in the
compositions of the
present invention. FD&C dyes (e.g., yellow #5, blue #2, red # 40) and / or
FD&C lakes are
preferably used. By adding the lakes to the other powdered ingredients, all
the particles, in
particular the colored iron compound, are completely and uniformly colored and
a uniformly
colored beverage mix is attained. Preferred lake dyes which may be used in the
present
invention are the FDA-approved Lake, such as Lake red #40, yellow #6, blue #1,
and the like.
Additionally, a mixture of FD&C dyes or a FD&C lake dye in combination with
other conventional
food and food colorants may be used. Riboflavin and b-carotene may also be
used. Additionally,
other natural coloring agents may be utilized including, for example, fruit,
vegetable, and / or plant
extracts such as grape, black currant, aronia, carrot, beetroot, red cabbage,
and hibiscus.
The amount of coloring agent used will vary, depending on the agents used and
the
intensity desired in the finished product. The amount can be readily
determined by one skilled in
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the art. Generally, if utilized, the coloring agent should be present at a
level of from about
0.0001 % to about 0.5%, preferably from about 0.001 % to about 0.1 %, and most
preferably from
about 0.004% to about 0.1 %, by weight of the composition.
Preservatives
Optionally, one or more preservatives may additionally be utilized herein.
Preferred
preservatives include, for example, sorbate, benzoate, and polyphosphate
preservatives.
Preferably, wherein a preservative is utilized herein, one or more sorbate or
benzoate
preservatives (or mixtures thereof) are utilized. Sorbate and benzoate
preservatives suitable for
use in the present invention include sorbic acid, benzoic acid, and salts
thereof, including (but not
limited to) calcium sorbate, sodium sorbate, potassium sorbate, calcium
benzoate, sodium
benzoate, potassium benzoate, and mixtures thereof. Sorbate preservatives are
particularly
preferred. Potassium sorbate is particularly preferred for use in the present
invention.
Wherein a composition comprises a preservative, the preservative is preferably
included
at levels from about 0.0005% to about 0.5%, more preferably from about 0.001 %
to about 0.4% of
the preservative, still more preferably from about 0.001 % to about 0.1 %,
even more preferably
from about 0.001 % to about 0.05%, and most preferably from about 0.003% to
about 0.03% of
the preservative, by weight of the composition. Wherein the composition
comprises a mixture of
one or more preservatives, the total concentration of such preservatives is
preferably maintained
within these ranges.
Emulsifiers and Oils
One or more emulsifiers and / or oils may also be included in the present
compositions
for texture and opacity purposes. Typical emulsifiers and oils useful herein
include, for example,
mono-di glycerides, lecithin, pulp, cotton seed oil, and vegetable oil.
Carbonation Component
Carbon dioxide can be introduced into the water which is mixed with a beverage
concentrate or into the beverage composition after dilution to achieve
carbonation. The
carbonated beverage can be placed into a container, such as a bottle or can,
and then sealed.
Any conventional carbonation methodology may be utilized to make carbonated
beverage
compositions of this invention. The amount of carbon dioxide introduced into
the beverage will
depend upon the particular flavor system utilized and the amount of
carbonation desired.
The Information Used in the Present Kits and Methods
In one embodiment of the present invention, the kits further comprise
information
selected from the group consisting of:
(i) dose-form information;
(ii) instruction or suggestion of ingestion of the composition within about 4
hours of
ingestion of a food or beverage; and
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(iii) combinations thereof.
As the present inventors have discovered, this information is critical to the
success of the
compositions herein. For example, the present inventors have surprisingly
discovered that the
behavior of the consumer in need of treatment affects the success of the
chondroprotective
regimen. In particular, the relationship between 1 ) ingestion of a particular
form of
chondroprotective composition; and 2) food or beverage intake has been found
to be critical to
the success of the regimen. Accordingly, the information described herein,
which guides the
consumer toward an optimized.regimen, is a critical and surprisingly effective
element of the
presentinvention.
Accordingly, the present kits comprise an aqueous chondroprotective
composition as well
as information which improves or aids efficacy of the composition. In
particular, the kits comprise
information which informs the consumer that aqueous chondroprotective
compositions provide
enhanced efficacy relative to dry-form chondroprotective compositions having
the same, or
similar, chondroprotective agent. Alternatively or additionally, the kits
comprise information which
instructs or suggests ingestion of the composition within about 4 hours of
ingestion of a food or
beverage. As the ordinarily skilled artisan will understand, the information
defined within the
present invention is not limited to specific words or descriptions herein.
As is well-known, language used to provide information can be modified
extensively
without substantially modifying the overall message to the consumer.
Accordingly, the
descriptions which follow are not intended to be limiting in any way, but
serve to exemplify the
particular information which is important for the success of the present
regimens.
The information included within the kit may be in the form of words, pictures,
symbols,
and / or the like. The information may, as non-limiting examples, be present
on: 1 ) a label visible
on the exterior of packaging (e.g., a label on a bottle, carrier, or case); or
2) a packaging insert
included within the packaging utilized (including, for example, within
carriers, cases, or even
under a bottle cap). Additionally, the information of the kit need not be
physically present with the
aqueous chondroprotective composition. For example, the information may be
associated with
the composition, for example, advertising or information accessible by
computer (e.g., the
Internet), television, print advertisement, and physician recommendations).
In a particularly preferred embodiment, the information is printed on a device
containing
the composition, e.g., a bottle. These preferred kits may be in the form of
one bottle containing
the composition, or may be obtained as a plurality of bottles each containing
the composition. For
example, the kits may be obtained as one bottle, or cases of four, six, seven
(e.g., a weekly
supply), or eight bottles co-packaged together. Additionally, monthly kits may
be obtained as
cases of, for example, twenty-eight or thirty bottles co-packaged together.
The information need not use the actual words described herein (e.g.,
"enhanced
efficacy"). The information is preferably presented in a manner such that the
consumer can
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readily understand and follow the instructions. Preferably, the information is
provided at a low
readability level, i.e., is written such that the average consumer can
understand the information.
Complex and difficult medical terminology or diagnostic indicators (e.g.,
photos showing a clinical
difference between subjects treated with traditional products and subjects
treated with the
compositions herein) are preferably translated into more simple words,
pictures, and / or symbols.
The readability level of the information is very important since it has been
reported that patients
do not understand many medical terms used in typical patient information
materials. See e.ct.,
D.L. Smith, "Compliance Packaging: A Patient Education Tool", Amer. Pharm.,
Vol. NS29, No. 2,
p. 42 - 53 (1989).
A. Dose-form Information
As stated, the present inventors have discovered that efficacy of
chondroprotective
compositions is unexpectedly related to the particular form of
chondroprotective composition
used. In particular, the present inventors have discovered that the aqueous
chondroprotective
compositions used herein provide substantially increased efficacy, and thus
health benefit,
relative to the corresponding dry-forms. As used herein, the "corresponding
dry-form" will contain
the same chondroprotective agents) as the aqueous chondroprotective
composition to which it is
compared. However, this "corresponding dry-form" comprises less than about 2%
water, by
weight of the dry-form composition.
Dry-form compositions comprise less than about 2% water, by weight of the
composition.
Preferably, dry-form compositions comprise less than about 1 % water, by
weight of the
composition. Most preferably, dry-form compositions comprise less than about
0.5% water, by
weight of the composition.
Non-limiting examples of dry-form compositions include tablets, capsules,
pills, granules,
and powders. Dry-form compositions are often compressed, tablet triturates,
enteric-coated,
sugar-coated, film-coated, or multiple-compressed, containing suitable
binders, lubricants,
diluents, disintegrating agents, coloring agents, flavoring agents, flow-
inducing agents, and
melting agents. Dry-form compositions will often contain one or more
conventional adjuvants
such as inert diluents, for example, calcium carbonate, sodium carbonate,
mannitol, lactose and
cellulose; binders such as starch, gelatin and sucrose; disintegrants such as
starch, alginic acid
and croscarmelose; lubricants such as magnesium stearate, stearic acid, and
talc. Glidants such
as silicon dioxide can be used to improve flow characteristics of the powder
mixture. Coloring
agents, such as the FD&C dyes are often added for appearance. Sweeteners and
flavoring
agents, such as aspartame, saccharin, menthol, peppermint, and fruit flavors,
are useful
adjuvants for chewable tablets.
As used herein, the "dose-form information" distinguishes efficacy of the
present aqueous
chondroprotective compositions from that exhibited by the foregoing dry-form
compositions. Such
information will inform the consumer (by words, pictures, symbols and / or the
like) that use of the
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aqueous chondroprotective present as part of the kit will exhibit enhanced
efficacy relative to a
dry-form composition, for example, a corresponding dry-form composition.
It is therefore necessary to inform the consumer that use of the present
aqueous
chondroprotective compositions will provide an enhanced health benefit (e.g.,
a joint health
benefit, bone health benefit, cardiac health benefit, and / or anti-
inflammation benefit) relative to
dry-form compositions). Preferably, the dose-form information will inform the
consumer that the
present aqueous chondroprotective compositions provide an enhanced joint
health benefit, bone
health benefit, and / or anti-inflammation benefit relative to the dry-form
composition. It is most
preferred to convey that a joint health benefit is optimized through use of
the present aqueous
chondroprotective compositions, relative to the dry-form composition.
Non-limiting examples of such dose-form information include the following
phrases (other
words, pictures, symbols, and / or the like can alternatively be used to
convey the same or similar
meaning):
1. "More efficacious than tablets or capsules."
2. "More efficacious than X-Brand Joint Improver" (i.e., any brand name of dry-
form
chondroprotective product).
3. "Works better than tablets, capsules, pills, or powders."
4. "Scientists have found that this product works better than the leading
tablets,
capsules, pills, and powders."
5. "Clinically-proven to provide better joint flexibility than the leading
tablet."
6. "Clinically-proven to decrease the pain associated with inflammation - even
better
than the leading tablet!"
7. "Helps restore your joint and bone health in a way that no tablet or
capsule can."
8. "Each day of treatment helps your joints better than the leading tablet."
9. "Just think - freedom from your symptoms is now nearer than when you took
the
leading tablet!"
10. "You are now in control of you symptoms - you have just purchased the best
available joint health product on the market."
11. "You can feel relief faster because this product is more efficacious and
more
bioavailable than tablets."
B. Instruction or Suq_gestion of Ingestion Within About 4 Hours of Ingestion
of a Food or
Beverage
As stated, the present inventors have discovered that efficacy of the
chondroprotective
composition is also enhanced wherein the composition is ingested within about
4 hours of
ingestion of a food or beverage, relative to not consuming a food or beverage
during this time
period. In addition to this finding, it has been surprisingly discovered that
the efficacy of aqueous
chondroprotective compositions is significantly greater relative to that of
dry forms of
CA 02408611 2002-11-05
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chondroprotective compositions (e.g., tablets or capsules), even wherein each
of these
compositions is ingested within about 4 hours of ingestion of a food or
beverage.
It has therefore been discovered that efficacy of the chondroprotective
regimen is
dependent upon food or beverage intake and, in order to provide efficacious
treatments,
consumers need to be aware of this discovery. Accordingly, the present kits
further comprise
information which is instruction or suggestion of ingestion of the
chondroprotective composition
within about 4 hours of ingestion of a food or beverage. As used herein,
"instruction of ingestion
of the composition" is information which instructs the consumer to ingest the
composition within
about 4 hours of ingestion of a food or beverage. As used herein, "suggestion
of ingestion of the
composition" is information which merely suggests this use or merely informs
the consumer that
certain results may be achieved when ingested within about 4 hours of
ingestion of a food or
beverage.
As also used herein, the term "ingested within about 4 hours of ingestion of a
food or
beverage" includes within both about 4 hours before or after ingestion of a
chondroprotective
composition described herein. Additionally, "within about 4 hours" includes
any amount of time
which is less than, or equal to, about 4 hours. For example, "within about 4
hours" includes within
about 3 hours, within about 2 hours, within about 1 hour, within about 45
minutes, and even
concurrently with ingestion of a food or beverage. As used herein,
"concurrently" means
ingestion of a chondroprotective composition as described herein at about the
same time as
ingesting a food or beverage, within about fifteen .to about thirty minutes
after completely
ingesting a food or beverage, or within about fifteen to about thirty minutes
before commencing
the ingestion of a food or beverage. As further used herein, the term
"concurrently" includes
instruction to ingest the chondroprotective composition "with a food or
beverage." Preferably, the
food or beverage is ingested within about 2 hours, more preferably within
about 1 hour, and most
preferably concurrently with, ingestion of the chondroprotective composition.
The chondroprotective composition may be in any form, e.g., a ready-to-drink
beverage
composition or a concentrate which is formulated by the consumer. Therefore,
"within about 4
hours of ingestion of a food or beverage" refers to a food or beverage which
is additional to the
chondroprotective composition ingested herein. The food or beverage ingested
is not limited and
need not be specifically described in the information (i.e., the information
may be "for best results,
take this product with the food of your choice"). Most preferably, the present
kits comprise
information that the aqueous chondroprotective composition should be ingested
within about 4
hours of ingestion of a food. Such food may be a full meal (e.g., a meal
comprised of a meat and
vegetable) or a snack (e.g., a piece of fruit, crackers, or a candy bar).
Therefore, the information
may instruct or suggest ingestion of a chondroprotective composition within 4
hours of ingestion
of breakfast, lunch, dinner, or a snack.
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The food or beverage preferably comprises at least one of a carbohydrate, fat,
or protein
source. Non-limiting examples of foods include fruits, vegetables, savory
snacks (e.g., potato
chips and pretzels), cracker snacks (e.g., cheese and cracker snacks), health
bars (e.g.,
PowerBar° (commercially available from PowerBar Inc., Berkeley, CA),
NutriGrain~ Bar
(commercially available from Kellogg's), HeartBar (commercially available from
Cooke Pharma,
Belmont, CA), and Clif Bar~ and Luna Bar~ (both commercially available from
Clif Bar, Inc.,
Berkeley, CA), and Prevesse~, commercially available from Procter & Gamble
Co., Cincinnati,
OH)), yogurts, cheeses, breads, cereals, meat products, rice products, and
baked goods (e.g.,
cookies and other snack foods). Most preferably, the food is.a health bar. Non-
limiting examples
of beverages include fruit juices (including all levels of fruit juice), milk
products, sodas, and
coffee products.
Preferably, the food or beverage is nutritionally-balanced. As used herein,
the term
"nutritionally-balanced", means that that a single serving or reference
serving of the food provides
a nutritionally desirable level of fat, protein or amino acid source, and
dietary fiber. Preferably,
"nutritionally balanced" foods provide a relatively low level of digestible
fat (e.g., about 3 grams or
less per reference serving and / or about 27% or less of total calories from
fat), are a good source
of dietary protein or other amino acid source (e.g., about 5 g or more per
reference serving and /
or about 19% or more of total calories from protein), and / or are a good
source of dietary fiber
(e.g., about 2.5 g or more of dietary fiber per reference serving). More
preferably, "nutritionally
balanced" foods provide a relatively low level of digestible fat (e.g., about
3 grams or less per
reference serving and / or about 27% or less of total calories from fat), are
a good source of
dietary protein or other amino acid source (e.g., about 5 g or more per
reference serving and
about 19% or more of total calories from protein), and / or are a good source
of dietary fiber (e.g.,
about 2.5 g or more of dietary fiber per reference serving).
Preferably, the kit is labeled with the time of day that the chondroprotective
composition is
to be administered, for example, "Breakfast", "Lunch", "Dinner" and / or
"Snack" (i.e., between,
before, and / or after a meal). This aids the consumer to ingest the aqueous
chondroprotective
composition with a meal or snack. It is a preferred embodiment of the present
invention to inform
or suggest the consumer to ingest the chondroprotective composition within 4
hours of ingestion
of breakfast or dinner, preferably breakfast.
Since ingestion of a food or beverage is important, the information of the kit
may also be,
for example, recipes and healthy diet literature which recommends the
ingestion of healthy foods
to the user.
Preferably, the information will inform the consumer that the present aqueous
chondroprotective compositions provide an enhanced joint health benefit, bone
health benefit,
and / or anti-inflammation when ingested within about 4 hours of ingestion of
a food or beverage.
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It is most preferred to convey that a joint health, bone health, and / or anti-
inflammation benefit is
enhanced. Most preferably, the information conveys that a joint health benefit
is enhanced.
Non-limiting examples of such information include the following phrases (other
words,
pictures, symbols, and / or the like can alternatively be used to convey the
same or similar
meaning):
1. "For best results, take this product with food or soft drink."
2. "For best results, take this product with your favorite meal."
3. "We suggest taking this product around the time of a meal or snack."
4. "For best results, take this product with a healthy diet."
5. "For best results, take this product with your favorite healthy meal - full
of proteins
and carbohydrates."
6. "Drink this product with breakfast for optimal performance."
7. "A healthy lifestyle includes eating the right meal before or after you
drink this
product."
8. "Your flexibility performance will be optimal if you take this product
around the time
you eat your favorite snack or meal."
9. "Your joints will appreciate a snack with this product!"
The Separate Food or Beverage of the Present Kits
In yet another embodiment of the present invention, the kits comprise:
(a) a composition comprising one or more chondroprotective agents and at least
about
80% water; and
(b) a separate food or beverage.
As has been stated, the present inventors have discovered that efficacy of the
chondroprotective composition is enhanced wherein the composition is ingested
within about 4
hours of a food or beverage, relative to not consuming a food or beverage
during this time period.
Therefore, as has been discovered, in order to provide an efficacious
chondroprotective regimen,
it is important for the consumer to have access not only to the composition
comprising the
chondroprotective agent, but also a separate food or beverage. This ensures
compliance with the
optimal regimen described herein, particularly for the modern consumer who is
extremely busy
with the tasks and responsibilities of daily life. It is understood herein
that the composition
comprising the chondroprotective agent and water may, and often will be, a
beverage
composition. Thus, the "separate food or beverage" is a distinct composition
which may be, for
example, a solid or semi-solid food, or even a further beverage composition.
Preferably, the kit
comprises a separate food. As will be understood herein, the importance is
that a source of one
or more of a carbohydrate, fat (lipid), protein, or other common food
component is included as a
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WO 01/93833 PCT/USO1/17721
composition which is separate from the chondroprotective composition also
provided within the
kit.
As stated, the separate food or beverage preferably comprises at least one of
a
carbohydrate, fat, or protein source. Non-limiting examples of separate foods
include fruits,
vegetables, savory snacks (e.g., potato chips and pretzels), cracker snacks
(e.g., cheese and
cracker snacks), health bars (e.g., PowerBar° (commercially available
from PowerBar Inc.,
Berkeley, CA), NutriGrain~ Bar (commercially available from Kellogg's),
HeartBar (commercially
available from Cooke Pharma, Belmont, CA), and Clif Bar° and Luna Bar~
(both commercially
available from Clif Bar, Inc., Berkeley, CA), and Prevesse~, commercially
available from Procter &
Gamble Co., Cincinnati, OH)), yogurts, cheeses, breads, cereals, meat
products, rice products,
and baked goods (e.g., cookies and other snack foods). Most preferably, the
separate food is a
health bar. Non-limiting examples of separate beverages include fruit juices
(including all levels
of fruit juice), milk products, sodas, and coffee products.
Preferably, the separate food or beverage is nutritionally-balanced. As used
herein, the
term "nutritionally-balanced", means that that a single serving or reference
serving of the food
provides a nutritionally desirable level of fat, protein or amino acid source,
arid dietary fiber.
Preferably, "nutritionally balanced" foods provide a relatively low level of
digestible fat (e.g., about
3 grams or less per reference serving and / or about 27% or less of total
calories from fat), are a
good source of dietary protein or other amino acid source (e.g., about 5 g or
more per reference
serving and l or about 19% or more of total calories from protein), and / or
are a good source of
dietary fiber (e.g., about 2.5 g or more of dietary fiber per reference
serving). More preferably,
"nutritionally balanced" foods provide a relatively low level of digestible
fat (e.g., about 3 grams or
less per reference serving and / or about 27% or less of total calories from
fat), are a good source
of dietary protein or other amino acid source (e.g., about 5 g or more per
reference serving and
about 19% or more of total calories from protein), and / or are a good source
of dietary fiber (e.g.,
about 2.5 g or more of dietary fiber per reference serving).
The kits comprising the separate food or beverage may optionally further
comprise:
(a) the foregoing dose-form information;
(b) the foregoing instruction or suggestion of ingestion of the composition
within about 4
hours of ingestion of the separate food or beverage; or
(c) combinations thereof.
Methods of the Present Invention
The methods of the present invention comprise enhancing a benefit associated
with a
composition comprising one or more chondroprotective agents and water, the
method comprising
orally administering to a mammal the composition within about 4 hours of oral
administration of a
food or beverage.
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The compositions are preferably administered to mammals who experience joint
and / or
bone dysfunction or those who desire to maintain current joint and / or bone
function (i.e.,
prophylactic use). The compositions of this invention may be ingested as a
supplement to normal
dietetic requirements. Frequency of administration is not limited, however,
such administration is
typically at least once weekly, more preferably at least 3 times weekly, and
most preferably at
least once daily.
As used herein, the term "orally administering" with respect to the mammal
(preferably,
human) means that the mammal ingests or is directed to ingest (preferably, for
the purpose of
providing joint and l or bone health): 1 ) one or more aqueous
chondroprotective compositions of
the present invention; and also according to the method 2) a food or beverage
within 4 hours of
administration of the composition. Preferably, the composition is a beverage
composition having
the foregoing preferred limitations. Preferably, the food or beverage is a
food, having the
foregoing preferred limitations. As set forth above, preferably the
composition is administered
within about 2 hours, more preferably within about 1 hour, and most preferably
concurrently with
administration of a food or beverage.
Wherein the mammal is directed to ingest one or more of the compositions or
the food or
beverage, such direction may be that which instructs and / or informs the user
that use of the
composition may and / or will provide one or more general health and / or
general physiological
benefits including, but not limited to, joint health, bone health, cardiac
health, anti-inflammation,
refreshment, satiation, and nutrition. Non-limiting examples of such
instruction or information is
set forth herein above as part of the description of the present kits.
For example, such direction may be oral direction (e.g., through oral
instruction from, for
example, a physician, health professional, sales professional or organization,
and l or radio or
television media (i.e., advertisement) or written direction (e.g., through
written direction from, for
example, a physician or other health ,professional (e.g., scripts), sales
professional or
organization (e.g., through, for example, marketing brochures, pamphlets, or
other instructive
paraphernalia), written media (e.g., Internet, electronic mail, or other
computer-related media),
and / or packaging associated with the composition (e.g., a label present on a
package containing
the composition). As used herein, "written" means through words, pictures,
symbols, and / or
other visible descriptors. Such direction need not utilize the actual words
used herein, for
example, "joint", "bone", "human", or "mammal", but rather use of words,
pictures, symbols, and
the like conveying the same or similar meaning are contemplated within the
scope of this
invention.
Methods of Making
The presently described aqueous chondroprotective compositions are made
according to
methods which will be well known by the ordinarily skilled artisan. To
illustrate, the compositions
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herein may be prepared by dissolving, dispersing, or otherwise mixing all
components singularly
or in suitable combinations together and in water where appropriate, agitating
with a mechanical
stirrer until all of the ingredients have been solubilized or adequately
dispersed. Where
appropriate, all separate solutions and dispersed may then be combined. When
using the
present chondroprotective agents which have been discovered to be pH sensitive
as described
herein, it may be important to adjust the desired pH with an acidulant and /
or buffer system
before adding the chondroprotective agent to the mixture. Wherein a shelf
stable composition is
desired, the final mixture can optionally, but preferably, be pasteurized or
filled aseptically at
appropriate process conditions.
In making a beverage composition, a beverage concentrate may optionally be
formed
first. One method to prepare the concentrate form of the beverage composition
would be to start
with less than the required volume of water that is used in the preparation of
the beverage
composition. Another method would be to partially dehydrate the finally
prepared beverage
compositions to remove only a portion of the water and any other volatile
liquids present.
Dehydration may be accomplished in accordance with well known procedures, such
as
evaporation under vacuum. The concentrate can be in the form of a relatively
thick liquid. A
syrup is typically formed by adding suitable ingredients such as electrolytes
or emulsions to the
beverage concentrate. The syrup is then mixed with water to form a finished
beverage or finished
beverage concentrate. The weight ratio of water to syrup is typically from
about 1:1 to about 5:1.
Carbon dioxide can be introduced either into the water to be mixed with the
beverage
concentrate, or into the ready-to-drink beverage composition, to achieve
carbonation. The
carbonated beverage composition can then be stored in a suitable container and
then sealed.
Techniques for making and carbonating beverage embodiments of the present
invention are
described in the following references: L.F. Green (ed.), Developments in Soft
Drinks Technology,
Vol. 1 (Elsevier, 1978); G.S. Cattell and P.M. Davies, "Preparation and
Processing of Fruit Juices,
Cordials and Drinks", Journal of the Society of Dairy Technology; Vol. 38 (1),
pp. 21-27, A.H.
Varnam and J.P. Sutherland, Beverages - Technology, Chemistry and
Microbiology, Chapman
Hall, 1994; and A.J. Mitchell (ed.), Formulation and Production of Carbonated
Soft Drinks, Blackie
and Sons Ltd., 1990.
EXAMPLES
The following are non-limiting examples of the present kits and methods. The
compositions utilized are prepared utilizing conventional methods. The
following examples are
provided to illustrate the invention and are not intended to limit the scope
thereof in any manner.
Example 1
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An 8 oz. ready-to-drink beverage composition is prepared by combining the
following
components in a conventional manner:
Component Wt%
Glucosamine Hydrochloride 0.8
Fructose 9.3
Thickeners 0.04
Calcium citrate malate 0.67
Fruit Juice Concentrate 1.65
Natural Flavors 0.02
Ascorbic Acid 0.04
Citric Acid 0.35
Water quantum satis
In a particularly preferred example of this beverage composition,
approximately 1800 mg of the
glucosamine hydrochloride is used in the composition. If needed, the pH of the
beverage
composition is adjusted to around 3.7. Various flavors of the beverage
composition may be
formulated according to standard techniques, for example, grapefruit and / or
cranberry flavors.
This composition is contained within a bottle. The bottle is labeled with
various information,
including the information described herein. The label states that "Best
results are achieved when
taking this product with food." The label also states that "This product
provides greater joint
health benefit relative to any benefit provided by the leading tablet or
capsule."
As a result of the labeled information, a 45-year-old human female orally
ingests the composition
concurrently with her daily breakfast, which typically includes buttered toast
and a banana. After
ingesting the composition once-daily for about 4 weeks, she reports enhanced
flexibility relative to
when she was ingesting corresponding dry-forms.
Example 2
A 4 oz. ready-to-drink beverage composition is prepared by combining the
following
components in a conventional manner:
Component Wt%
Glucosamine Hydrochloride 1.6
Fructose 9.3
Thickeners 0.04
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Calcium citrate malate 1.14
Fruit Juice Concentrate 1.65
Natural Flavors 0.02
Ascorbic Acid 0.08
Citric Acid 0.35
Water quantum satis
If needed, the pH of the beverage composition is adjusted to from about 3.7 to
about 3.9. Various
flavors of the beverage composition may be formulated according to standard
techniques, for
example, grapefruit and / or cranberry flavors. If desired, this beverage
composition may be
further diluted by the consumer prior to ingestion with additional water, or a
beverage of the
consumer's choice.
This composition is contained within a bottle. The bottle is labeled with
various information,
including the information described herein. The label instructs the consumer
to "Take this product
within about 1 hour of eating your favorite snack or meal." The label also
instructs the consumer
to "Take this product as a superior substitute to the leading capsule or
tablet."
As a result of the labeled information, a ~50-year-old human male orally
ingests the composition.
After ingesting the composition once-daily for about 4 weeks concurrently with
his daily dinner,
which typically includes meat and vegetables (e.g., a salad), he reports
decreased joint pain
relative to when he was ingesting corresponding dry-forms.
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Example 3
A 2 oz, ready-to-drink beverage composition is prepared by combining the
following
components in a conventional manner:
Component Wt%
Glucosamine Hydrochloride 3.2
Fructose 9.3
Thickeners 0.04
Calcium citrate malate 2.3
Natural Flavors 0.02
Ascorbic Acid 0.16
Citric Acid 0.35
Water quantum satis
If needed, the pH of the beverage composition is adjusted to from about 3.7 to
about 3.9. Various
flavors of the beverage composition may be formulated according to standard
techniques, for
example, grapefruit and / or cranberry flavors. If desired, this beverage
composition may be
further diluted by the consumer prior to ingestion with additional water, or a
beverage of the
consumer's choice.
This composition is contained within a bottle. The bottle is labeled with
various information,
including the information described herein. The label instructs the consumer
to "Add this to the
water you provide with your pet's daily meal." The label also instructs the
consumer to "Feed this
as a substitute to the leading dry powder."
As a result of the labeled information, the owner of a large dog administers
the composition to the
dog. After the dog ingests the composition once-daily with his daily meal for
about 4 weeks, the
owner reports that the dog exhibits increased physical activity (including
running and jumping)
relative to when the dog was ingesting corresponding dry-forms.
Example 4
A kit according to the present invention comprises the composition according
to Example
1 and a distinct, nutritionally-balariced health bar composition (having a
filling (according to the
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"filling formula") sandwiched between two "crackers" (according to the crumb
formula) and having
the following composition:
Ingredient Crumb Formula Filling
grams/100 grams Formula
grams/100
rams
62DE Corn Syrup (Quality Ingredients-0.61
Corp.,
Chester, N.J.
Olean~ Procter & Gamble Co., Cincinnati,8.95 22.2
OH.
Malt Syrup (Hawkeye 5900 Quality 1.22
Ingredients
Cor .,Chester N.J.
Natural Butter Flavor (Flavors 1.47
of North America,
Inc., Carol Stream, IL.
Processed De-fatted (20%) Peanut 49.8
Flour from
US#1 Medium Runner Peanuts (Cargill
Peanut,
Dawson GA.
Su ar 12X Amal amated Su ar Co.,O 13.8
den, UT.
Granulated Su ar Holl Su ar Co., 5.49
Worland,WY.
Salt - TFC Purex (Morton International,0.29
Inc.,
Philadel hia, PA.
Iodized Salt (Morton International, 1.1
Inc., Chicago,
I L.
L-Cysteine HCI Monohydrate (Quality.041
Ingredients
Cor .,Chester N.J.
Lecithin - Centrophase HR (Central .2
Soya Co., Inc.,
Fort Wa ne, IN.
Flour - soft wheat (Siemer Milling40.28
Co., Teutopolis,
IL.
Fiber- insoluble wheat (Vitacel~ 2.94
WF-600/30,
J.Rettenmaier, Ellwan en/J, German
Fiberaid~ Larex Cor ., White Bear1.47 9.0
Lake, MN.
Isolated Soy Protein (Supro~ 661,6.27 3.5
Protein
Technolo ies Intl., St. Louis,
MO.
Sodium Bicarbonate (Church & DwightI 0.74
Co.,
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Princeton, NJ.
Calcium Phosphate Monobasic (Regent0.59
12XX,
Rhodia, Cranbu , N.J.
Sodium Aluminum Phosphate (Levair,0.59
Rhodia,
Cranbu , N.J.
Ammonium Bicarbonate (Church & 1.86
Dwight Co.,
Princeton, NJ.
Whey Protein Isolate (BiPRO, Davisco2.69
Food
International, Inc., Le Sueur,
MN.
Water 19.40
Wheat Gluten (Gluvital 21000, 1.96
Cerestar,
Hammond, IN.
Calcium Carbonate (USP AIbaGlos, 1.96
Specialty
Minerals, Inc., Bethlehem, PA.
Egg White Solids (Henningsen Foods,0.98
Omaha,
NE.
Constant Behenic Stabilizer ADM, 0.4
Macon, GA.
Vitamin Mix: Com onents & ratios 0.8
as listed below
Vitamin A,D3, IC1 blend (Watson 39.09
Foods Co., West
Haven, CT.
Vit E alpha-tocopherol acetate 19.81
50% type CWS/F
Roche Vitamins, Parsi an , NJ.
(vit B1 ) Thiamine Hydrochloride 0.75
(Roche Vitamins,
Parsi an , NJ.
(vit B2) Riboflavin (Roche Vitamins, 0.82
Parsippany,
NJ.
(vit B3) Niacin USP FCC (Roche 7.19
Vitamins,
Parsi an , NJ.
(vit B6) Pyridoxine Hydrochloride 0.96
(Roche Vitamins,
Parsi an , NJ.
(vit B12) 1 % Trituration of Vitamin 0.25
B12 (Roche
Vitamins, Parsi an , NJ.
Vitamin C ultra fine powder (Roche 21.55
Vitamins,
Parsi an , NJ.
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Zinc Citrate Trih drate Tate & 6.88
L 1e, Decatur, IL.
Iron (reduced) (100% ) (Roche 2.64
Vitamins,
Parsi an , NJ.
The health bar is manufactured under standard conditions well-known to one of
ordinary skill in
the art.
As stated in Example 1, the chondroprotective composition is contained within
a bottle.
The bottle is labeled with various information, including the information
described herein. The
label states that "Best results are achieved when taking this product with
food." The label also
states that "This product provides greater joint health benefit relative to
any benefit provided by
the leading tablet or capsule."
The health bar is packaged in a standard plastic wrapper, the
chondroprotective
composition is contained within a bottle, and the two of these are co-packaged
(e.g., inside a
containing device such as a box) as the kit. A 30-year-old athletic male
obtains the kit, eats the
health bar, and drinks the chondroprotective composition 'over a 15 minute
period.
37
