Note: Descriptions are shown in the official language in which they were submitted.
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DESCRIPTION
NUTRITIONAL COMPOSITIONS CONTAINING BUTYRATE
AND USES THEREOF
TECHNICAL FIELD
[0001] The present disclosure relates generally to nutritional compositions
comprising
dietary butyrate that are suitable for administration to pediatric subjects.
Additionally,
the disclosure relates to methods for improving the shelf-stability of
nutritional
compositions including dietary butyrate, and methods for improving the
organoleptic
properties of nutritional compositions including dietary butyrate. The
disclosed
nutritional compositions may provide additive and or/synergistic beneficial
health
effects.
BACKGROUND ART
[0002] Administration of nutritional compositions or other compositions
including
butyrate or butyrate derivatives often suffer from difficulties regarding the
availability of
butyrate upon administration. For example, certain butyrate derivatives
undergo
degradation or oxidation, which ultimate affect the bioavailability of the
butyrate
derivative upon ingestion. As such, compositions including butyrate
derivatives may not
provide nutritional efficacy upon ingestion given the degradation of the
butyrate
derivative.
[0003] Additionally, nutritional compositions including butyrate may suffer
from poor
palatability. The unpleasant taste and odor of compositions including butyrate
can
make the oral administration of certain nutritional compositions including
butyrate
difficult, especially in the pediatric population. For example, certain
butyric acid
derivatives at room temperature are present as a dense liquid having an
unpleasant
intense odor.
[0004] Accordingly, it would be beneficial to provide a nutritional
composition that
includes dietary butyrate having improved shelf-stability and organoleptic
properties.
Additionally, it is beneficial to provide methods of producing a nutritional
composition
including dietary butyrate having improved shelf stability and organoleptic
properties.
DISCLOSURE OF THE INVENTION
[0005] Briefly, the present disclosure is directed, in an embodiment, to a
nutritional
composition that includes dietary butyrate. In some embodiments, the dietary
butyrate
may be encapsulated. In some embodiments, the dietary butyrate may be provided
by an enriched lipid fraction derived from milk.
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[0006] In certain embodiments, the nutritional composition includes dietary
butyrate
that has improved organoleptic properties. In some embodiments, the
nutritional
composition including dietary butyrate has improved shelf-stability.
[0007] Additionally, the disclosure is directed to a methods for improving the
shelf
stability and/or organoleptic properties of a nutritional composition
including dietary
butyrate.
[0008] It is to be understood that both the foregoing general description and
the
following detailed description present embodiments of the disclosure and are
intended
to provide an overview or framework for understanding the nature and character
of
the disclosure as it is claimed. The description serves to explain the
principles and
operations of the claimed subject matter. Other and further features and
advantages
of the present disclosure will be readily apparent to those skilled in the art
upon a
reading of the following disclosure.
BEST MODE FOR CARRYING OUT THE INVENTION
[0009] Reference now will be made in detail to the embodiments of the present
disclosure, one or more examples of which are set forth herein below. Each
example is
provided by way of explanation of the nutritional composition of the present
disclosure
and is not a limitation. In fact, it will be apparent to those skilled in the
art that various
modifications and variations can be made to the teachings of the present
disclosure
without departing from the scope of the disclosure. For instance, features
illustrated or
described as part of one embodiment, can be used with another embodiment to
yield
a still further embodiment.
[0010] Thus, it is intended that the present disclosure covers such
modifications and
variations as come within the scope of the appended claims and their
equivalents.
Other objects, features and aspects of the present disclosure are disclosed in
or are
apparent from the following detailed description. It is to be understood by
one of
ordinary skill in the art that the present discussion is a description of
exemplary
embodiments only and is not intended as limiting the broader aspects of the
present
disclosure.
[0011] The present disclosure relates generally to nutritional compositions
comprising
dietary butyrate. Additionally, the disclosure relates to methods for
improving the shelf
stability and/or organoleptic properties of nutritional compositions including
butyrate.
[0012] "Nutritional composition" means a substance or formulation that
satisfies at least
a portion of a subject's nutrient requirements. The terms "nutritional(s)",
"nutritional
formula(s)", "enteral nutritional(s)", and "nutritional supplement(s)" are
used as non-
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limiting examples of nutritional composition(s) throughout the present
disclosure.
Moreover, "nutritional composition(s)" may refer to liquids, powders, gels,
pastes, solids,
concentrates, suspensions, or ready-to-use forms of enteral formulas, oral
formulas,
formulas for infants, formulas for pediatric subjects, formulas for children,
growing-up
milks and/or formulas for adults.
[0013] "Pediatric subject" means a human less than 13 years of age. In some
embodiments, a pediatric subject refers to a human subject that is between
birth and
8 years old. In other embodiments, a pediatric subject refers to a human
subject
between 1 and 6 years of age. In still further embodiments, a pediatric
subject refers to
a human subject between 6 and 12 years of age. The term "pediatric subject"
may
refer to infants (preterm or fullterm) and/or children, as described below.
[0014] "Infant" means a human subject ranging in age from birth to not more
than one
year and includes infants from 0 to 12 months corrected age. The phrase
"corrected
age" means an infant's chronological age minus the amount of time that the
infant
was born premature. Therefore, the corrected age is the age of the infant if
it had
been carried to full term. The term infant includes low birth weight infants,
very low
birth weight infants, and preterm infants. "Preterm" means an infant born
before the
end of the 37'" week of gestation. "Full term" means an infant born after the
end of the
37'" week of gestation.
[0015] "Child" means a subject ranging in age from 12 months to about 13
years. In
some embodiments, a child is a subject between the ages of 1 and 12 years old.
In
other embodiments, the terms "children" or "child" refer to subjects that are
between
one and about six years old, or between about seven and about 12 years old. In
other
embodiments, the terms "children" or "child" refer to any range of ages
between 12
months and about 13 years.
[0016] "Infant formula" means a composition that satisfies at least a portion
of the
nutrient requirements of an infant. In the United States, the content of an
infant formula
is dictated by the federal regulations set forth at 21 C.F.R. Sections 100,
106, and 107.
[0017] "Fractionation procedure" includes any process in which a certain
quantity of a
mixture is divided up into a number of smaller quantities known as fractions.
The
fractions may be different in composition from both the mixture and other
fractions.
Examples of fractionation procedures include but are not limited to melt
fractionation,
solvent fractionation, supercritical fluid fractionation and/or combinations
thereof.
[0018] "Milk fat globule membrane" includes components found in the milk fat
globule
membrane including but not limited to milk fat globule membrane proteins such
as
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Mucin 1, Butyrophilin, Adipophilin, CD36, CD14, Lactadherin (PAS6/7), Xanthine
oxidase
and Fatty Acid binding proteins etc.
[0019] The term "growing-up milk" refers to a broad category of nutritional
compositions intended to be used as a part of a diverse diet in order to
support the
normal growth and development of a child between the ages of about 1 and about
6
years of age.
[0020] "Milk" means a component that has been drawn or extracted from the
mammary gland of a mammal. In some embodiments, the nutritional composition
comprises components of milk that are derived from domesticated ungulates,
ruminants or other mammals or any combination thereof.
[0021] "Nutritionally complete" means a composition that may be used as the
sole
source of nutrition, which would supply essentially all of the required daily
amounts of
vitamins, minerals, and/or trace elements in combination with proteins,
carbohydrates,
and lipids. Indeed, "nutritionally complete" describes a nutritional
composition that
provides adequate amounts of carbohydrates, lipids, essential fatty acids,
proteins,
essential amino acids, conditionally essential amino acids, vitamins, minerals
and
energy required to support normal growth and development of a subject.
[0022] A nutritional composition that is "nutritionally complete" for a full
term infant will,
by definition, provide qualitatively and quantitatively adequate amounts of
all
carbohydrates, lipids, essential fatty acids, proteins, essential amino acids,
conditionally
essential amino acids, vitamins, minerals, and energy required for growth of
the full
term infant.
[0023] A nutritional composition that is "nutritionally complete" for a child
will, by
definition, provide qualitatively and quantitatively adequate amounts of all
carbohydrates, lipids, essential fatty acids, proteins, essential amino acids,
conditionally
essential amino acids, vitamins, minerals, and energy required for growth of a
child.
[0024] "Dietary butyrate" as used herein refers to butyrate and butyrate
derivatives.
Non-limiting examples of dietary butyrate include butyric acid, butyrate
salts, and
glycerol esters of butyric acid.
[0025] The term "degree of hydrolysis" refers to the extent to which peptide
bonds are
broken by a hydrolysis method. The degree of protein hydrolysis for purposes
of
characterizing the hydrolyzed protein component of the nutritional composition
is
easily determined by one of ordinary skill in the formulation arts by
quantifying the
amino nitrogen to total nitrogen ratio (AN/TN) of the protein component of the
selected formulation. The amino nitrogen component is quantified by USP
titration
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methods for determining amino nitrogen content, while the total nitrogen
component
is determined by the Kjeldahl method, all of which are well known methods to
one of
ordinary skill in the analytical chemistry art.
[0026] When a peptide bond in a protein is broken by enzymatic hydrolysis, one
amino
group is released for each peptide bond broken, causing an increase in amino
nitrogen. It should be noted that even non-hydrolyzed protein would contain
some
exposed amino groups. Hydrolyzed proteins will also have a different molecular
weight
distribution than the non-hydrolyzed proteins from which they were formed. The
functional and nutritional properties of hydrolyzed proteins can be affected
by the
different size peptides. A molecular weight profile is usually given by
listing the percent
by weight of particular ranges of molecular weight (in Daltons) fractions
(e.g., 2,000 to
5,000 Daltons, greater than 5,000 Daltons).
[0027] The term "molar mass distribution" when used in reference to a
hydrolyzed
protein or protein hydrolysate pertains to the molar mass of each peptide
present in
the protein hydrolysate. For example, a protein hydrolysate having a molar
mass
distribution of greater than 500 Daltons means that each peptide included in
the
protein hydrolysate has a molar mass of at least 500 Daltons. To produce a
protein
hydrolysate having a molar mass distribution of greater than 500 Daltons, a
protein
hydrolysate may be subjected to certain filtering procedures or any other
procedure
known in the art for removing peptides, amino acids, and/or other
proteinaceous
material having a molar mass of less than 500 Daltons. For the purposes of
this
disclosure, any method known in the art may be used to produce the protein
hydrolysate having a molar mass distribution of greater than 500 Dalton.
[0028] The term "protein equivalent" or "protein equivalent source" includes
any
protein source, such as soy, egg, whey, or casein, as well as non-protein
sources, such
as peptides or amino acids. Further, the protein equivalent source can be any
used in
the art, e.g., nonfat milk, whey protein, casein, soy protein, hydrolyzed
protein, amino
acids, and the like. Bovine milk protein sources useful in practicing the
present
disclosure include, but are not limited to, milk protein powders, milk protein
concentrates, milk protein isolates, nonfat milk solids, nonfat milk, nonfat
dry milk, whey
protein, whey protein isolates, whey protein concentrates, sweet whey, acid
whey,
casein, acid casein, caseinate (e.g. sodium caseinate, sodium calcium
caseinate,
calcium caseinate), soy bean proteins, and any combinations thereof. The
protein
equivalent source can, in some embodiments comprise hydrolyzed protein,
including
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partially hydrolyzed protein and extensively hydrolyzed protein. The protein
equivalent
source may, in some embodiments, include intact protein.
[0029] The term "protein equivalent source" also encompasses free amino acids.
In
some embodiments, the amino acids may comprise, but are not limited to,
histidine,
isoleucine, leucine, lysine, methionine, cysteine, phenylalanine, tyrosine,
threonine,
tryptophan, valine, alanine, arginine, asparagine, aspartic acid, glutamic
acid,
glutamine, glycine, praline, serine, carnitine, taurine and mixtures thereof.
In some
embodiments, the amino acids may be branched chain amino acids. In certain
other
embodiments, small amino acid peptides may be included as the protein
component
of the nutritional composition. Such small amino acid peptides may be
naturally
occurring or synthesized.
[0030] The term "partially hydrolyzed" means having a degree of hydrolysis
which is
greater than 0% but less than about 50%.
[0031] The term "extensively hydrolyzed" means having a degree of hydrolysis
which is
greater than or equal to about 50%. Accordingly, "extensively hydrolyzed
casein
fraction(s)" means casein having a degree of hydrolysis which is greater than
or equal
to about 50%. In some embodiments, extensively hydrolyzed may include a degree
of
hydrolysis of greater than about 80%. In further embodiments, extensively
hydrolyzed
may include a degree of hydrolysis of greater than about 90%.
[0032] The term "protein-free" means containing no measurable amount of intact
protein, as measured by standard protein detection methods such as sodium
dodecyl
(lauryl) sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) or size
exclusion
chromatography. In some embodiments, the nutritional composition is
substantially
free of protein, wherein "substantially free" is defined hereinbelow.
[0033] The nutritional composition of the present disclosure may be
substantially free of
any optional or selected ingredients described herein, provided that the
remaining
nutritional composition still contains all of the required ingredients or
features described
herein. In this context, and unless otherwise specified, the term
"substantially free"
means that the selected composition may contain less than a functional amount
of the
optional ingredient, typically less than 0.1% by weight, and also, including
zero percent
by weight of such optional or selected ingredient.
[0034] All percentages, parts and ratios as used herein are by weight of the
total
composition, unless otherwise specified.
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[0035] All references to singular characteristics or limitations of the
present disclosure
shall include the corresponding plural characteristic or limitation, and vice
versa, unless
otherwise specified or clearly implied to the contrary by the context in which
the
reference is made.
[0036] All combinations of method or process steps as used herein can be
performed in
any order, unless otherwise specified or clearly implied to the contrary by
the context in
which the referenced combination is made.
[0037] The methods and compositions of the present disclosure, including
components
thereof, can comprise, consist of, or consist essentially of the essential
elements and
limitations of the embodiments described herein, as well as any additional or
optional
ingredients, components or limitations described herein or otherwise useful in
nutritional
compositions.
[0038] As used herein, the term "about" should be construed to refer to both
of the
numbers specified as the endpoint(s) of any range. Any reference to a range
should
be considered as providing support for any subset within that range.
[0039] The present disclosure is directed to nutritional compositions
including dietary
butyrate. The nutritional compositions may further include a carbohydrate
source, a
protein source, and a fat source.
[0040] In some embodiments, the nutritional composition includes a source of
dietary
butyrate that is present in an amount of from about 0.2 g/100 g fatty acids to
about 1.8
g/100 g fatty acids where the fat source constitutes from about 4 g fat/100
Kcal to
about 6 g fat/100 Kcal.
[0041] In some embodiments the dietary butyrate is provided by one or more of
the
following: butyric acid; butyrate salts, including sodium butyrate, potassium
butyrate,
calcium butyrate, and/or magnesium butyrate; glycerol esters of butyric acid;
and/or
corresponding mixtures and corresponding salts of pharmaceutically acceptable
bases or acids, pure diastereoisomeric forms and enantiomeric forms or
mixtures
thereof.
[0042] In some embodiments, the dietary butyrate is supplied by any suitable
source
known in the art. Non-limiting sources of dietary butyrate includes animal
source fats
and derived products, such as but not limited to milk, milk fat, butter,
buttermilk, butter
serum, cream,; microbial fermentation derived products, such as but not
limited to
yogurt, fermented buttermilk, cheese, beverages; and plant source derived seed
oil
products, such as pineapple, and apricot. In some embodiments, the dietary
butyrate
is synthetically produced. In embodiments where the dietary butyrate is
synthetically
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produced, the chemical structure of the dietary butyrate can be formed and
modified
as necessary. Further, the dietary butyrate produced synthetically can be
purified by
any means known in the art to produce a purified dietary butyrate additive
that can
be incorporated into the nutritional compositions disclosed herein.
[0043] In some embodiments, the dietary butyrate may be provided in an
encapsulated form. In certain embodiments, the encapsulation of the dietary
butyrate
may provide for longer shelf-stability and may provide for improved
organoleptic
properties of the nutritional composition. For example, in some embodiments,
the
dietary butyrate may be coated or encapsulated by the use of, or combination
of, fat
derived materials, such as mono- and di-glycerides, sugar and acid esters of
glycerides, phospholipids; plant, animal and microbial derived proteins and
hydrocolloids, such as starches, maltodextrins, gelatin, pectins, glucans,
caseins, soy
proteins, whey proteins.
[0044] In certain embodiments, the dietary butyrate comprises glycerol esters
of butyric
acid and/or alkyl esters of butyric acid. Glycerol esters of butyric acid may
offer
minimal complexity when formulated and processed in the nutritional
composition.
Additionally, glycerol esters of butyric acid may improve the shelf life of
the nutritional
composition including dietary butyrate and may further have a low impact on
the
sensory attributes of the finished product.
[0045] In some embodiments, dietary butyrate may comprise butyric acid amide
derivatives using other amino acids, for example, tyrosine and/or histidine.
In some
embodiments, any suitable amino acid known in the art may be utilized in
preparing
the butyric acid amide derivative used as a source of dietary butyrate.
Without being
bound by any particular theory, it is believed that dietary butyrate comprised
of butyric
acid amide derivatives may resist the action of gastric acids and the
processing
conditions encountered in nutritional composition, such as infant formula,
manufacturing. Accordingly, in embodiments where the dietary butyrate is
provided
by one or more butyric acid amide derivatives the resulting nutritional
composition
includes a stable dietary butyrate formulation with improved organoleptic
properties.
[0046] The dietary butyrate may in some embodiments comprise butyrate salts,
for
example, sodium butyrate, potassium butyrate, calcium butyrate, magnesium
butyrate, and combinations thereof. In some embodiments, the use of selected
dietary butyrate salts may improve intestinal health when provided to target
subjects.
In certain embodiments, dietary butyrate comprises a suitable butyrate salt
that has
been coated with one or more fats or lipids. In certain embodiments wherein
the
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dietary butyrate comprises a fat coated butyrate salt, the nutritional
composition may
be a dry-powdered composition into which the dietary butyrate is incorporated.
[0047] In embodiments, the dietary butyrate may comprise any of the butyrate
compounds disclosed herein that are formulated to be in complex form with
chitosan
or one or more cyclodextrins. For example, cyclodextrins are cyclic
oligosaccharides
composed of six (a-cyclodextrin), seven (P-cyclodextrin), or eight (gamma-
cyclodextrin) units of a-1,4-glucopyranose. Cyclodextrins are further
characterized by
a hydrophilic exterior surface and a hydrophobic core. Without being bound by
any
particular theory, the aliphatic butyrate chain would form a complex with the
cyclodextrin core, thus increasing its molecular weight and, thus, reducing
the volatility
of the butyrate compound. Accordingly, the bioavailability of dietary butyrate
may be
improved when the dietary butyrate includes butyrate compounds in complex form
with one or more cyclodextrins. Further, cyclodextrins are bulky hydrophobic
molecules
that are resistant to stomach acid as well as gastrointestinal enzymes, thus
administration of the butyrate-cyclodextrin complex as described herein would
promote absorption of the dietary butyrate in the small intestine.
[0048] The dietary butyrate can be provided from an enriched lipid fraction
derived
from milk in certain embodiments. For example, bovine milk fat has a butyric
acid
content that may be 20 times higher than the butyric acid content present in
human
milk fat. Furthermore, among the short chain fatty acids ("SCFAs") present in
human
milk, i.e. fatty acids having a carbon chain length from 4 to 12, butyric acid
(C4) is one
of the most predominant in bovine milk. As such, bovine milk fat and/or
enriched
fractions of bovine milk fat may be included in a nutritional composition to
provide
dietary butyrate.
[0049] In embodiments where the dietary butyrate is provided by an enriched
lipid
fraction derived from milk the enriched lipid fraction derived from milk may
be
produced by any number of fractionation techniques. These techniques include
but
are not limited to melting point fractionation, organic solvent fractionation,
super
critical fluid fractionation, and any variants and combinations thereof.
[0050] Furthermore, mixtures that may be subjected to the fractionation
procedures to
produce the enriched lipid fraction include, but are not limited to, bovine
whole milk,
bovine cream, caprine milk, ovine milk, yak milk and/or mixtures thereof. In a
preferred
embodiment the milk mixture used to create the enriched lipid fraction is
bovine milk.
[0051] In addition to providing dietary butyrate, the enriched lipid fraction
may
comprise an one of the following ingredients: saturated fatty acids; trans-
fatty acids;
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branched-chain fatty acids ("BCFAs"), including odd-branched chain fatty acids
("OBCFAs"); conjugated linoleic acid ("CLA"); monounsaturated fatty acids;
polyunsaturated fatty acids; cholesterol; phospholipids; and milk fat globule
membrane, including milk fat globule membrane protein.
[0052] In some embodiments the enriched lipid fraction includes, per 100 Kcal,
one or
more of the following:
from about 0.1 g to 8.0 g of saturated fatty acids;
from about 0.2 g to 7.0 g trans-fatty acids;
from about 0.003 g to about 6.1 g branched-chain fatty acids;
from about 0.026 g to about 2.5 g conjugated linoleic acid;
from about 0.8 g to about 2.5 g monounsaturated fatty acids;
from about 2.3 g to about 4.4 g polyunsaturated fatty acids;
from about 100 mg to about 400 mg of cholesterol;
from about 50 mg to about 400 mg of phospholipids; and/or
from about 10 mg to about 500 mg of milk fat globule membrane.
Example 1
[0053] Illustrated below are two lipid profiles of fractionated milk fat
produced by super
critical carbon extraction fractionation procedure and by melt-fractionation.
g/100 g fatty acids
SCCO2- MeltFrac*-
C 4:0 5.95 4.67
C 6:0 3.28 2.89
C 8:0 1.91 1.76
C 10:0 3.90 3.83
C 12:0 4.14 4.81
C 14:0 12.18 10.87
C 14:1 1.00 1.32
C 15:0 1.03 0.94
C 16:0 29.55 22.27
C 16:1 1.37 2.21
C 17:0 0.50 0.42
C 18:0 8.16 6.08
C 18:1, cis, c,39 16.47 25.27
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18:1, trans,
C co9 1.64 1.88
C 18:2, co 6 2.16 1.90
C 18:3, co 3, co 0.40 0.59
C 20:0 0.06 0.06
C 20:1, co 9 0.08 0.17
Saturated 70.66 58.59
Unsaturated 23.13 33.34
*SCCO2 = super-critical carbon dioxide fraction (super olein).
** MeltFrac = melt crystallization fraction separated at 10 C.
[0054] In certain embodiments, dietary butyrate is incorporated into a
nutritional
composition that is an infant formula. Certain butyrate compounds, such as
acid salts
and alkyl esters of butyric acid, exhibit an odor that makes consuming the
nutritional
composition in which they are incorporated an unpleasant experience.
Furthermore,
the pediatric and infant population will not readily consume products having
an
unpleasant odor, taste, and/or mouthfeel. Accordingly, there exists a need for
a
nutritional composition formulated for administration to a pediatric subject
or an infant
that includes dietary butyrate yet does not have diminished organoleptic
properties.
The incorporation of certain dietary butyrate compounds disclosed herein, i.e.
glycerol
esters of butyric acid, butyrate enriched milk fat fractions, and amide
derivatives of
amino acids, into pediatric and infant nutritional compositions will provide a
source of
dietary butyrate while still providing a pleasant sensory experience.
[0055] The nutritional composition(s) of the present disclosure may also
comprise a
carbohydrate source. Carbohydrate sources can be any used in the art, e.g.,
lactose,
glucose, fructose, corn syrup solids, maltodextrins, sucrose, starch, rice
syrup solids, and
the like. The amount of carbohydrate in the nutritional composition typically
can vary
from between about 5 g and about 25 g/100 Kcal. In some embodiments, the
amount
of carbohydrate is between about 6 g and about 22 g/ 100 Kcal. In other
embodiments, the amount of carbohydrate is between about 12 g and about 14
g/100 Kcal. In some embodiments, corn syrup solids are preferred. Moreover,
hydrolyzed, partially hydrolyzed, and/or extensively hydrolyzed carbohydrates
may be
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desirable for inclusion in the nutritional composition due to their easy
digestibility.
Specifically, hydrolyzed carbohydrates are less likely to contain allergenic
epitopes.
[0056] Non-limiting examples of carbohydrate materials suitable for use herein
include
hydrolyzed or intact, naturally or chemically modified, starches sourced from
corn,
tapioca, rice or potato, in waxy or non-waxy forms. Non-limiting examples of
suitable
carbohydrates include various hydrolyzed starches characterized as hydrolyzed
cornstarch, maltodextrin, maltose, corn syrup, dextrose, corn syrup solids,
glucose, and
various other glucose polymers and combinations thereof. Non-limiting examples
of
other suitable carbohydrates include those often referred to as sucrose,
lactose,
fructose, high fructose corn syrup, indigestible oligosaccharides such as
fructooligosaccharides and combinations thereof.
[0057] The nutritional composition(s) of the disclosure may also comprise a
protein
source. The protein source can be any used in the art, e.g., nonfat milk, whey
protein,
casein, soy protein, hydrolyzed protein, amino acids, and the like. Bovine
milk protein
sources useful in practicing the present disclosure include, but are not
limited to, milk
protein powders, milk protein concentrates, milk protein isolates, nonfat milk
solids,
nonfat milk, nonfat dry milk, whey protein, whey protein isolates, whey
protein
concentrates, sweet whey, acid whey, casein, acid casein, caseinate (e.g.
sodium
caseinate, sodium calcium caseinate, calcium caseinate) and any combinations
thereof.
[0058] In one embodiment, the proteins of the nutritional composition are
provided as
intact proteins. In other embodiments, the proteins are provided as a
combination of
both intact proteins and partially hydrolyzed proteins, with a degree of
hydrolysis of
between about 4% and 10%. In certain other embodiments, the proteins are more
completely hydrolyzed. In still other embodiments, the protein source
comprises amino
acids. In yet another embodiment, the protein source may be supplemented with
glutamine-containing peptides.
[0059] In some embodiments, the nutritional composition may include a protein
equivalent source, wherein at least 1% of the protein equivalent source
comprises
extensively hydrolyzed casein and up to 99% of the protein equivalent source
comprises an intact protein, a partially hydrolyzed protein, amino acids, or
combinations thereof. In embodiments, 1% to 80% of the protein equivalent
source
comprises extensively hydrolyzed casein and 20% to 99% of the protein
equivalent
source comprises intact protein, partially hydrolyzed protein, amino acids, or
combinations thereof. In still other embodiments, from 40% to 100% of the
protein
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13
equivalent source comprises extensively hydrolyzed casein and from 0 to 60% of
the
protein equivalent source comprises an intact protein, a partially hydrolyzed
protein,
amino acids, or combinations thereof. In yet other embodiments, from 40% to
70% of
the protein equivalent source comprises extensively hydrolyzed casein and from
30% to
60% of the protein equivalent source comprises an intact protein, a partially
hydrolyzed
protein, amino acids, or combinations thereof.
[0060] In some embodiments, extensively hydrolyzed casein may be present in
the
nutritional composition in an amount from about 0.2 g/100 kcal to about 5.6
g/100 kcal.
In other embodiments extensively hydrolyzed casein may be present in the
nutritional
composition in an amount from about 1 g/100 kcal to about 4 g/100 kcal. In
still other
embodiments, extensively hydrolyzed casein may be present in the nutritional
composition in an amount from about 2 g/100 kcal to about 3 g/100 kcal.
[0061] The protein equivalent source disclosed herein may be formulated with
other
ingredients in the nutritional composition to provide appropriate nutrient
levels for the
target subject. In some embodiments, the protein equivalent source is included
in a
nutritionally complete formula that is suitable to support normal growth.
[0062] In some embodiments, the protein equivalent source comprises a
hydrolyzed
protein, such as casein, which includes partially hydrolyzed protein and
extensively
hydrolyzed protein (i.e., the extensively hydrolyzed casein). In some
embodiments, the
extensively hydrolyzed casein comprises an extensively hydrolyzed casein
and/or
fractions thereof including peptides having a molar mass distribution of
greater than
500 Da!tons. In some embodiments, the extensively hydrolyzed casein comprises
peptides having a molar mass distribution in the range of from about 500
Daltons to
about 1,500 Da!tons. Still, in some embodiments the extensively hydrolyzed
casein may
comprise peptides having a molar mass distribution range of from about 500
Da!tons to
about 2,000 Da!tons.
[0063] In some embodiments the protein equivalent source comprises partially
hydrolyzed protein having a degree of hydrolysis of less than 40%. In still
other
embodiments, the protein equivalent source may comprise partially hydrolyzed
protein
having a degree of hydrolysis of less than 25%, or less than 15%.
[0064] In a particular embodiment, the nutritional composition is protein-free
and
contains free amino acids as a protein equivalent source. In this embodiment,
the
amino acids may comprise, but are not limited to, histidine, isoleucine,
leucine, lysine,
methionine, cysteine, phenylalanine, tyrosine, threonine, tryptophan, valine,
alanine,
arginine, asparagine, aspartic acid, glutamic acid, glutamine, glycine,
proline, serine,
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carnitine, taurine and mixtures thereof. In some embodiments, the amino acids
may
be branched chain amino acids. In other embodiments, small amino acid peptides
may be included as the protein component of the nutritional composition. Such
small
amino acid peptides may be naturally occurring or synthesized. The amount of
free
amino acids in the nutritional composition may vary from about 1 to about 5
g/100
kcal. In an embodiment, 100% of the free amino acids have a molecular weight
of less
than 500 Daltons. In this embodiment, the nutritional composition may be
hypoallergenic.
[0065] In an embodiment, where the protein equivalent source comprises intact
proteins, the intact proteins comprise from about 40% to about 85% whey
protein and
from about 15% to about 60% casein.
[0066] In a particular embodiment of the nutritional composition, the
whey:casein ratio
of the protein source is similar to that found in human breast milk. In an
embodiment,
the protein source comprises from about 40% to about 80% whey protein and from
about 20% to about 60% casein.
[0067] In some embodiments, the nutritional composition comprises between
about 1 g
and about 7 g of a protein source per 100 Kcal. In other embodiments, the
nutritional
composition comprises between about 3.5 g and about 4.5 g of protein per 100
Kcal.
[0068] In some embodiments, the nutritional composition described herein
comprises a
fat source. The enriched lipid fraction described herein may be the sole fat
source or
may be used in combination with any other suitable fat or lipid source for the
nutritional
composition as known in the art. Appropriate fat sources include, but are not
limited
to, animal sources, e.g., milk fat, butter, butter fat, egg yolk lipid; marine
sources, such
as fish oils, marine oils, single cell oils; vegetable and plant oils, such as
corn oil, canola
oil, sunflower oil, soybean oil, palm olein oil, coconut oil, high oleic
sunflower oil,
evening primrose oil, rapeseed oil, olive oil, flaxseed (linseed) oil,
cottonseed oil, high
oleic safflower oil, palm stearin, palm kernel oil, wheat germ oil; medium
chain
triglyceride oils and emulsions and esters of fatty acids; and any
combinations thereof.
[0069] In some embodiments the nutritional composition may also include a
source of
long chain polyunsaturated fatty acids (LCPUFAs). In one embodiment the amount
of
LCPUFA in the nutritional composition is advantageously at least about 5
mg/100 Kcal,
and may vary from about 5 mg/100 Kcal to about 100 mg/100 Kcal, more
preferably
from about 10 mg/100 Kcal to about 50 mg/100 Kcal. Non-limiting examples of
LCPUFAs include, but are not limited to, docosahexaenoic acid (DHA),
arachidonic
acid (ARA), linoleic (18:2 n-6), y-linolenic (18:3 n-6), dihomo- y-linolenic
(20:3 n-6) acids
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in the n-6 pathway, a-linolenic (18:3 n-3), stearidonic (18:4 n-3),
eicosatetraenoic (20:4
n-3), eicosapentaenoic (20:5 n-3), and docosapentaenoic (22:6 n-3).
[0070] In some embodiments, the LCPUFA included in the nutritional composition
may
comprise DHA. In one embodiment the amount of DHA in the nutritional
composition is
advantageously at least about 17 mg/100 Kcal, and may vary from about 5 mg/100
Kcal to about 75 mg/100 Kcal, more preferably from about 10 mg/100 Kcal to
about 50
mg/100 Kcal.
[0071] In another embodiment, especially if the nutritional composition is an
infant
formula, the nutritional composition is supplemented with both DHA and ARA. In
this
embodiment, the weight ratio of ARA:DHA may be between about 1:3 and about
9:1.
In a particular embodiment, the ratio of ARA:DHA is from about 1:2 to about
4:1.
[0072] The DHA and ARA can be in natural form, provided that the remainder of
the
LCPUFA source does not result in any substantial deleterious effect on the
infant.
Alternatively, the DHA and ARA can be used in refined form.
[0073] The disclosed nutritional composition described herein can, in some
embodiments, also comprise a source of B-glucan. Glucans are polysaccharides,
specifically polymers of glucose, which are naturally occurring and may be
found in
cell walls of bacteria, yeast, fungi, and plants. Beta glucans (B-glucans) are
themselves
a diverse subset of glucose polymers, which are made up of chains of glucose
monomers linked together via beta-type glycosidic bonds to form complex
carbohydrates.
[0074] 13-1,3-glucans are carbohydrate polymers purified from, for example,
yeast,
mushroom, bacteria, algae, or cereals. (Stone BA, Clarke AE. Chemistry and
Biology of
(1-3)-Beta-Glucans. London:Portland Press Ltd; 1993.) The chemical structure
of 13-1,3-
glucan depends on the source of the 13-1,3-glucan. Moreover, various
physiochemical
parameters, such as solubility, primary structure, molecular weight, and
branching, play
a role in biological activities of 13-1,3-glucans. (Yadomae T., Structure and
biological
activities of fungal beta- l,3-glucans. Yakugaku Zasshi. 2000;120:413-431.)
[0075] 13-1,3-glucans are naturally occurring polysaccharides, with or without
13-1,6-
glucose side chains that are found in the cell walls of a variety of plants,
yeasts, fungi
and bacteria. 13-1,3;1,6-glucans are those containing glucose units with (1,3)
links
having side chains attached at the (1,6) position(s). 13-1,3;1,6 glucans are a
heterogeneous group of glucose polymers that share structural commonalities,
including a backbone of straight chain glucose units linked by a 13-1,3 bond
with13-1,6-
linked glucose branches extending from this backbone. While this is the basic
structure
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for the presently described class of 13-glucans, some variations may exist.
For example,
certain yeast P-glucans have additional regions of 13(1,3) branching extending
from the
13(1,6) branches, which add further complexity to their respective structures.
[0076] 13-glucans derived from baker's yeast, Saccharomyces cerevisiae, are
made up
of chains of D-glucose molecules connected at the 1 and 3 positions, having
side
chains of glucose attached at the 1 and 6 positions. Yeast-derived 13-glucan
is an
insoluble, fiber-like, complex sugar having the general structure of a linear
chain of
glucose units with a 13-1,3 backbone interspersed with 13-1,6 side chains that
are
generally 6-8 glucose units in length. More specifically,13-glucan derived
from baker's
yeast is poly-(1,6)-13-D-glucopyranosyl-(1,3)-13-D-glucopyranose.
[0077] Furthermore,13-glucans are well tolerated and do not produce or cause
excess
gas, abdominal distension, bloating or diarrhea in pediatric subjects.
Addition of 13-
glucan to a nutritional composition for a pediatric subject, such as an infant
formula, a
growing-up milk or another children's nutritional product, will improve the
subject's
immune response by increasing resistance against invading pathogens and
therefore
maintaining or improving overall health.
[0078] In some embodiments, the 13-glucan is13-1,3;1,6-glucan. In some
embodiments,
the 13-1,3;1,6-glucan is derived from baker's yeast. The nutritional
composition may
comprise whole glucan particle 13-glucan, particulate P-glucan, PGG-glucan
(poly-1,6-
13-D-glucopyranosy1-1,313-D-glucopyranose) or any mixture thereof.
[0079] In some embodiments, the amount of 13-glucan in the nutritional
composition is
between about 3 mg and about 17 mg per 100 Kcal. In another embodiment the
amount of 13-glucan is between about 6 mg and about 17 mg per 100 Kcal.
[0080] The disclosed nutritional composition described herein can, in some
embodiments, also comprise a source of probiotic. The term "probiotic" means a
microorganism that exerts beneficial effects on the health of the host. Any
probiotic
known in the art may be acceptable in this embodiment. In a particular
embodiment,
the probiotic may be selected from any Lactobacillus species, Lactobacillus
rhamnosus
GG (ATCC number 53103), Bifidobacterium species, Bifidobacterium iongum BB536
(BL999, ATCC: BAA-999), Bifidobacterium longum AH1206 (NCIMB: 41382),
Bifidobacterium breve AH1205 (NCIMB: 41387), Bifidobacterium infantis 35624
(NCIMB:
41003), and Bifidobacterium animalis subsp. lactis BB-12 (DSM No. 10140) or
any
combination thereof.
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[0081] If included, the nutritional composition may comprise between about 1 x
104 to
about 1.5 x 10' cfu of probiotics per 100 Kcal, more preferably from about 1
x 106 to
about 1 x 109 cfu of probiotics per 100 Kcal.
[0082] In an embodiment, the probiotic (s) may be viable or non-viable. As
used
herein, the term "viable", refers to live microorganisms. The term "non-
viable" or "non-
viable probiotic" means non-living probiotic microorganisms, their cellular
components
and/or metabolites thereof. Such non-viable probiotics may have been heat-
killed or
otherwise inactivated, but they retain the ability to favorably influence the
health of
the host. The probiotics useful in the present disclosure may be naturally-
occurring,
synthetic or developed through the genetic manipulation of organisms, whether
such
new source is now known or later developed.
[0083] The disclosed nutritional composition described herein can, in some
embodiments, also comprise a source of prebiotics. The term "prebiotic" as
used herein
refers to indigestible food ingredients which exert health benefits upon the
host. Such
health benefits may include, but are not limited to, selective stimulation of
the growth
and/or activity of one or a limited number of beneficial gut bacteria,
stimulation of the
growth and/or activity of ingested probiotic microorganisms, selective
reduction in gut
pathogens, and favorable influence on gut short chain fatty acid profile. Such
prebiotics may be naturally-occurring, synthetic, or developed through the
genetic
manipulation of organisms and/or plants, whether such new source is now known
or
developed later. Prebiotics useful in the present disclosure may include
oligosaccharides, polysaccharides, and other prebiotics that contain fructose,
xylose,
soya, galactose, glucose and mannose.
[0084] More specifically, prebiotics useful in the present disclosure may
include
polydextrose, polydextrose powder, lactulose, lactosucrose, raffinose, gluco-
oligosaccharide, inulin, fructo-oligosaccharide, isomalto-oligosaccharide,
soybean
oligosaccharides, lactosucrose, xylo-oligosaccharide, chito-oligosaccharide,
manno-
oligosaccharide, aribino-oligosaccharide, siallyl-oligosaccharide, fuco-
oligosaccharide, galacto-oligosaccharide, and gentio-oligosaccharides. In one
preferred embodiment, the prebiotic comprises galacto-oligosaccharide,
polydextrose, or mixtures thereof.
[0085] The amount of galacto-oligosaccharide in the nutritional composition
may, in an
embodiment, be from about 0.1 g/100 Kcal to about 1.5 g/100 Kcal. In another
embodiment, the amount of galacto-oligosaccharide in the nutritional
composition
may be from about 0.1 g/100 Kcal to about 1.0 g/100 Kcal. The amount of
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polydextrose in the nutritional composition may, in an embodiment, be within
the
range of from about 0.1 g/100 Kcal to about 1.5 g/100 Kcal. In a particular
embodiment, galacto-oligosaccharide and polydextrose are supplemented into the
nutritional composition in a total amount of about at least about 0.2 g/100
Kcal and
can be about 0.2 g/100 Kcal to about 1.5 g/100 Kcal. In some embodiments, the
nutritional composition may comprise galactooligosaccharide and polydextrose
in a
total amount of from about 0.6 to about .8 g/100 Kcal.
[0086] The disclosed nutritional composition described herein, can, in some
embodiments also comprise an effective amount of iron. The iron may comprise
encapsulated iron forms, such as encapsulated ferrous fumarate or encapsulated
ferrous sulfate or less reactive iron forms, such as ferric pyrophosphate or
ferric
orthophosphate.
[0087] One or more vitamins and/or minerals may also be added in to the
nutritional
composition in amounts sufficient to supply the daily nutritional requirements
of a
subject. It is to be understood by one of ordinary skill in the art that
vitamin and mineral
requirements will vary, for example, based on the age of the child. For
instance, an
infant may have different vitamin and mineral requirements than a child
between the
ages of one and thirteen years. Thus, the embodiments are not intended to
limit the
nutritional composition to a particular age group but, rather, to provide a
range of
acceptable vitamin and mineral components.
[0088] In embodiments providing a nutritional composition for a child, the
composition
may optionally include, but is not limited to, one or more of the following
vitamins or
derivations thereof: vitamin B1 (thiamin, thiamin pyrophosphate, TPP, thiamin
triphosphate, TTP, thiamin hydrochloride, thiamin mononitrate), vitamin B2
(riboflavin,
flavin mononucleotide, FMN, flavin adenine dinucleotide, FAD, lactoflavin,
ovoflavin),
vitamin B3 (niacin, nicotinic acid, nicotinamide, niacinamide, nicotinamide
adenine
dinucleotide, NAD, nicotinic acid mononucleotide, NicMN, pyridine-3-carboxylic
acid),
vitamin B3-precursor tryptophan, vitamin B6 (pyridoxine, pyridoxal,
pyridoxamine,
pyridoxine hydrochloride), pantothenic acid (pantothenate, panthenol), folate
(folic
acid, folacin, pteroylglutamic acid), vitamin B12 (cobalamin, methylcobalamin,
deoxyadenosylcobalamin, cyanocobalamin, hydroxycobalamin, adenosylcobalamin),
biotin, vitamin C (ascorbic acid), vitamin A (retinol, retinyl acetate,
retinyl palmitate,
retinyl esters with other long-chain fatty acids, retinal, retinoic acid,
retinol esters),
vitamin D (calciferol, cholecalciferol, vitamin D3, 1,25,-dihydroxyvitamin D),
vitamin E (a-
tocopherol, a-tocopherol acetate, a-tocopherol succinate, a-tocopherol
nicotinate,
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a-tocopherol), vitamin K (vitamin K1, phylloquinone, naphthoquinone, vitamin
K2,
menaquinone-7, vitamin K3, menaquinone-4, menadione, menaquinone-8,
menaquinone-8H, menaquinone-9, menaquinone-9H, menaquinone-10,
menaquinone-11, menaquinone-12, menaquinone-13), choline, inositol, 13-
carotene
and any combinations thereof.
[0089] In embodiments providing a children's nutritional product, such as a
growing-up
milk, the composition may optionally include, but is not limited to, one or
more of the
following minerals or derivations thereof: boron, calcium, calcium acetate,
calcium
gluconate, calcium chloride, calcium lactate, calcium phosphate, calcium
sulfate,
chloride, chromium, chromium chloride, chromium picolonate, copper, copper
sulfate,
copper gluconate, cupric sulfate, fluoride, iron, carbonyl iron, ferric iron,
ferrous
fumarate, ferric orthophosphate, iron trituration, polysaccharide iron,
iodide, iodine,
magnesium, magnesium carbonate, magnesium hydroxide, magnesium oxide,
magnesium stearate, magnesium sulfate, manganese, molybdenum, phosphorus,
potassium, potassium phosphate, potassium iodide, potassium chloride,
potassium
acetate, selenium, sulfur, sodium, docusate sodium, sodium chloride, sodium
selenate,
sodium molybdate, zinc, zinc oxide, zinc sulfate and mixtures thereof. Non-
limiting
exemplary derivatives of mineral compounds include salts, alkaline salts,
esters and
chelates of any mineral compound.
[0090] The minerals can be added to growing-up milks or to other children's
nutritional
compositions in the form of salts such as calcium phosphate, calcium glycerol
phosphate, sodium citrate, potassium chloride, potassium phosphate, magnesium
phosphate, ferrous sulfate, zinc sulfate, cupric sulfate, manganese sulfate,
and sodium
selenite. Additional vitamins and minerals can be added as known within the
art.
[0091] The nutritional compositions of the present disclosure may optionally
include one
or more of the following flavoring agents, including, but not limited to,
flavored
extracts, volatile oils, cocoa or chocolate flavorings, peanut butter
flavoring, cookie
crumbs, vanilla or any commercially available flavoring. Examples of useful
flavorings
include, but are not limited to, pure anise extract, imitation banana extract,
imitation
cherry extract, chocolate extract, pure lemon extract, pure orange extract,
pure
peppermint extract, honey, imitation pineapple extract, imitation rum extract,
imitation
strawberry extract, or vanilla extract; or volatile oils, such as balm oil,
bay oil, bergamot
oil, cedarwood oil, cherry oil, cinnamon oil, clove oil, or peppermint oil;
peanut butter,
chocolate flavoring, vanilla cookie crumb, butterscotch, toffee, and mixtures
thereof.
The amounts of flavoring agent can vary greatly depending upon the flavoring
agent
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used. The type and amount of flavoring agent can be selected as is known in
the art.
[0092] The nutritional compositions of the present disclosure may optionally
include one
or more emulsifiers that may be added for stability of the final product.
Examples of
suitable emulsifiers include, but are not limited to, lecithin (e.g., from egg
or soy), alpha
lactalbumin and/or mono- and di-glycerides, and mixtures thereof. Other
emulsifiers
are readily apparent to the skilled artisan and selection of suitable
emulsifier(s) will
depend, in part, upon the formulation and final product.
[0093] The nutritional compositions of the present disclosure may optionally
include one
or more preservatives that may also be added to extend product shelf life.
Suitable
preservatives include, but are not limited to, potassium sorbate, sodium
sorbate,
potassium benzoate, sodium benzoate, calcium disodium EDTA, and mixtures
thereof.
[0094] The nutritional compositions of the present disclosure may optionally
include one
or more stabilizers. Suitable stabilizers for use in practicing the
nutritional composition of
the present disclosure include, but are not limited to, gum arabic, gum
ghatti, gum
karaya, gum tragacanth, agar, furcellaran, guar gum, gellan gum, locust bean
gum,
pectin, low methoxyl pectin, gelatin, microcrystalline cellulose, CMC (sodium
carboxymethylcellulose), methylcellulose hydroxypropyl methyl cellulose,
hydroxypropyl cellulose, DATEM (diacetyl tartaric acid esters of mono- and
diglycerides), dextran, carrageenans, and mixtures thereof.
[0095] The nutritional compositions of the disclosure may provide minimal,
partial or
total nutritional support. The compositions may be nutritional supplements or
meal
replacements. The compositions may, but need not, be nutritionally complete.
In an
embodiment, the nutritional composition of the disclosure is nutritionally
complete and
contains suitable types and amounts of lipid, carbohydrate, protein, vitamins
and
minerals. The amount of lipid or fat typically can vary from about 1 to about
25 g/100
Kcal. The amount of protein typically can vary from about 1 to about 7 g/100
Kcal. The
amount of carbohydrate typically can vary from about 6 to about 22 g/100 Kcal.
[0096] In an embodiment, the children's nutritional composition may contain
between
about 10 and about 50% of the maximum dietary recommendation for any given
country, or between about 10 and about 50% of the average dietary
recommendation
for a group of countries, per serving of vitamins A, C, and E, zinc, iron,
iodine, selenium,
and choline. In another embodiment, the children's nutritional composition may
supply about 10- 30% of the maximum dietary recommendation for any given
country,
or about 10- 30% of the average dietary recommendation for a group of
countries,
per serving of B-vitamins. In yet another embodiment, the levels of vitamin D,
calcium,
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magnesium, phosphorus, and potassium in the children's nutritional product may
correspond with the average levels found in milk. In other embodiments, other
nutrients in the children's nutritional composition may be present at about
20% of the
maximum dietary recommendation for any given country, or about 20% of the
average dietary recommendation for a group of countries, per serving.
[0097] In some embodiments the nutritional composition is an infant formula.
Infant
formulas are fortified nutritional compositions for an infant. The content of
an infant
formula is dictated by federal regulations, which define macronutrient,
vitamin,
mineral, and other ingredient levels in an effort to simulate the nutritional
and other
properties of human breast milk. Infant formulas are designed to support
overall
health and development in a pediatric human subject, such as an infant or a
child.
[0098] In some embodiments, the nutritional composition of the present
disclosure is a
growing-up milk. Growing-up milks are fortified milk-based beverages intended
for
children over 1 year of age (typically from 1-3 years of age, from 4-6 years
of age or
from 1-6 years of age). They are not medical foods and are not intended as a
meal
replacement or a supplement to address a particular nutritional deficiency.
Instead,
growing-up milks are designed with the intent to serve as a complement to a
diverse
diet to provide additional insurance that a child achieves continual, daily
intake of all
essential vitamins and minerals, macronutrients plus additional functional
dietary
components, such as non-essential nutrients that have purported health-
promoting
properties.
[0099] The exact composition of a growing-up milk or other nutritional
composition
according to the present disclosure can vary from market-to-market, depending
on
local regulations and dietary intake information of the population of
interest. In some
embodiments, nutritional compositions according to the disclosure consist of a
milk
protein source, such as whole or skim milk, plus added sugar and sweeteners to
achieve desired sensory properties, and added vitamins and minerals. The fat
composition includes an enriched lipid fraction derived from milk. Total
protein can be
targeted to match that of human milk, cow milk or a lower value. Total
carbohydrate is
usually targeted to provide as little added sugar, such as sucrose or
fructose, as
possible to achieve an acceptable taste. Typically, Vitamin A, calcium and
Vitamin D
are added at levels to match the nutrient contribution of regional cow milk.
Otherwise,
in some embodiments, vitamins and minerals can be added at levels that provide
approximately 20% of the dietary reference intake (DRI) or 20% of the Daily
Value (DV)
per serving. Moreover, nutrient values can vary between markets depending on
the
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identified nutritional needs of the intended population, raw material
contributions and
regional regulations.
[0100] The disclosed nutritional composition(s) may be provided in any form
known in
the at such as a powder, a gel, a suspension, a paste, a solid, a liquid, a
liquid
concentrate, a reconstituteable powdered milk substitute or a ready-to-use
product.
The nutritional composition may, in certain embodiments, comprise a
nutritional
supplement, children's nutritional product, infant formula, human milk
fortifier, growing-
up milk or any other nutritional composition designed for an infant or a
pediatric
subject. Nutritional compositions of the present disclosure include, for
example, orally-
ingestible, health-promoting substances including, for example, foods,
beverages,
tablets, capsules and powders. Moreover, the nutritional composition of the
present
disclosure may be standardized to a specific caloric content, it may be
provided as a
ready-to-use product, or it may be provided in a concentrated form. In some
embodiments, the nutritional composition is in powder form with a particle
size in the
range of 5 pm to 1500 pm, more preferably in the range of 10 pm to 300pm.
[0101] In certain embodiments, the disclosure is directed to a method of
producing a
nutritional composition comprising dietary butyrate that has improved
organoleptic
properties. For example, in certain embodiments, the nutritional composition
includes
dietary butyrate that has been encapsulated or coated according to the
disclosure
provided herein.
[0102] All combinations of method or process steps as used herein can be
performed in
any order, unless otherwise specified or clearly implied to the contrary by
the context in
which the referenced combination is made.
[0103] The methods and compositions of the present disclosure, including
components
thereof, can comprise, consist of, or consist essentially of the essential
elements and
limitations of the embodiments described herein, as well as any additional or
optional
ingredients, components or limitations described herein or otherwise useful in
nutritional
compositions.
[0104] Formulation examples are provided to illustrate some embodiments of the
nutritional composition of the present disclosure but should not be
interpreted as any
limitation thereon. Other embodiments within the scope of the claims herein
will be
apparent to one skilled in the art from the consideration of the specification
or practice
of the nutritional composition or methods disclosed herein. It is intended
that the
specification, together with the example, be considered to be exemplary only,
with the
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scope and spirit of the disclosure being indicated by the claims which follow
the
example.
FORMULATION EXAMPLES
Table 1
[0105] Table 1, illustrated below, provides an example embodiment of the
nutritional
profile of a nutritional composition including dietary butyrate and describes
the
amount of each ingredient to be included per 100 Kcal serving of nutritional
composition.
Table 1. Nutrition profile of an example nutritional composition including
dietary
butyrate
per 100 Kcal
Nutrient! Lipid
Minimum Maximum
Protein (g) 1.2 6.8
Fat total including enriched lipid
fraction (g) 1.4 10.3
Carbohydrates (g) 6 22
Prebiotic (g) 0.3 1.2
DHA (mg) 4 32
Beta glucan (mg) 2.9 17
Saturated Fatty acids (g) 0.1 2.3
Trans-fatty acid (g) 0.1 1.2
OBCFAs (g) 0.05 1.0
CLA (g) 0.05 1.0
Cholesterol (mg) 100 400
Milk Phospholipids (mg) 50 500
Phosphotidylcholine (mg) 130 400
SphingoMyelin (mg) 5 60
BCFAs (g) 0.3 2.3
Probiotics (cfu) 9.60x 108 3.80x 108
Vitamin A (IU) 134 921
Vitamin D (IU) 22 126
Vitamin E (IU) 0.8 5.4
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24
Vitamin K (mcg) 2.9 18
Thiamin (mcg) 63 328
Riboflavin (mcg) 68 420
Vitamin B6 (mcg) 52 397
Vitamin B12 (mcg) 0.2 0.9
Niacin (mcg) 690 5881
Folic acid (mcg) 8 66
Panthothenic acid (mcg) 232 1211
Biotin (mcg) 1.4 5.5
Vitamin C (mg) 4.9 24
Choline (mg) 4.9 43
Calcium (mg) 68 297
Phosphorus (mg) 54 210
Magnesium (mg) 4.9 34
Sodium (mg) 24 88
Potassium (mg) 82 346
Chloride (mg) 53 237
Iodine (mcg) 8.9 79
Iron (mg) 0.7 2.8
Zinc (mg) 0.7 2.4
Manganese (mcg) 7.2 41
Copper (mcg) 16 331
[0106] All references cited in this specification, including without
limitation, all papers,
publications, patents, patent applications, presentations, texts, reports,
manuscripts,
brochures, books, internet postings, journal articles, periodicals, and the
like, are hereby
incorporated by reference into this specification in their entireties. The
discussion of the
references herein is intended merely to summarize the assertions made by their
authors
and no admission is made that any reference constitutes prior art. Applicants
reserve
the right to challenge the accuracy and pertinence of the cited references.
[0107] Although embodiments of the disclosure have been described using
specific
terms, devices, and methods, such description is for illustrative purposes
only. The
words used are words of description rather than of limitation. It is to be
understood that
changes and variations may be made by those of ordinary skill in the art
without
departing from the spirit or the scope of the present disclosure, which is set
forth in the
CA 03004737 2018-05-08
WO 2017/083067 PCT/US2016/057641
following claims. In addition, it should be understood that aspects of the
various
embodiments may be interchanged in whole or in part. Therefore, the spirit and
scope
of the appended claims should not be limited to the description of the
versions
contained therein.
