U.S. patent application number 16/693738 was filed with the patent office on 2020-03-19 for nutritional compositions containing an elevated level of inositol and uses thereof.
The applicant listed for this patent is Mead Johnson Nutrition Company. Invention is credited to Dirk Hondmann, Chenzhong Kuang, Colin Rudolph, Yan Xiao.
Application Number | 20200085762 16/693738 |
Document ID | / |
Family ID | 55919923 |
Filed Date | 2020-03-19 |
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United States Patent
Application |
20200085762 |
Kind Code |
A1 |
Kuang; Chenzhong ; et
al. |
March 19, 2020 |
Nutritional Compositions Containing An Elevated Level Of Inositol
And Uses Thereof
Abstract
A nutritional composition including no greater than about 7
g/100 kcal of a fat or lipid source; no greater than about 7 g/100
kcal of a protein or protein equivalent source; at least about 5
g/100 kcal of a carbohydrate; and at least about 9 mg/100 kcal of
inositol, wherein the inositol comprises exogenous inositol and
inherent inositol, and wherein the ratio of exogenous inositol to
inherent inositol is at least 75:25.
Inventors: |
Kuang; Chenzhong; (Newburgh,
IN) ; Xiao; Yan; (Newburgh, IN) ; Rudolph;
Colin; (San Francisco, CA) ; Hondmann; Dirk;
(Winnetka, IL) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Mead Johnson Nutrition Company |
Evansville |
IN |
US |
|
|
Family ID: |
55919923 |
Appl. No.: |
16/693738 |
Filed: |
November 25, 2019 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
14729132 |
Jun 3, 2015 |
10525016 |
|
|
16693738 |
|
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|
|
Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61K 31/715 20130101;
A61K 47/42 20130101; A61K 31/047 20130101; A23V 2250/641 20130101;
A61K 47/26 20130101; A23V 2002/00 20130101; A23V 2200/322 20130101;
A23L 33/40 20160801; A61K 47/12 20130101; A23V 2002/00 20130101;
A23V 2200/322 20130101; A23V 2250/641 20130101 |
International
Class: |
A61K 31/047 20060101
A61K031/047; A23L 33/00 20060101 A23L033/00; A61K 31/715 20060101
A61K031/715; A61K 47/12 20060101 A61K047/12; A61K 47/26 20060101
A61K047/26; A61K 47/42 20060101 A61K047/42 |
Claims
1. A nutritional composition for enhancing neurological health and
development in a subject, the nutritional composition comprising: a
fat or lipid; a protein or protein equivalent; a carbohydrate; and
inositol, wherein the inositol comprises exogenous inositol and
inherent inositol, and wherein a ratio of the exogenous inositol to
the inherent inositol is at least 75:25.
2. The nutritional composition of claim 1, which further comprises
a long chain polyunsaturated fatty acid.
3. The nutritional composition of claim 2, wherein the long chain
polyunsaturated fatty acid comprises at least one of
docosahexaenoic acid, arachidonic acid, and combinations
thereof.
4. The nutritional composition of claim 2, wherein the long chain
polyunsaturated fatty acid is present from about 5 mg/100 kcal to
about 75 mg/100 kcal.
5. The nutritional composition of claim 1 further comprising
docosahexaenoic acid, arachidonic acid, phosphatidylethanolamines,
sphingomyelin, alpha-lipoic acid, epigallocatechin gallate,
sulforaphane, or combinations thereof.
6. The nutritional composition of claim 1 further comprising about
10 mg/100 kcal to about 200 mg/100 kcal of lactoferrin.
7. The nutritional composition of claim 1 further comprising a
prebiotic composition comprising polydextrose and
galactooligosaccharides, wherein the prebiotic composition
comprises at least 20% w/w polydextrose and galactooligosaccharides
and mixtures thereof.
8. The nutritional composition of claim 1, wherein the nutritional
composition is an infant formula or a growing up milk.
9. The nutritional composition of claim 1, wherein the nutritional
composition comprises: no greater than about 7 g/100 kcal of the
fat or lipid; no greater than about 7 g/100 kcal of the protein or
protein equivalent; at least about 5 g/100 kcal of the
carbohydrate; and at least about 9 mg/100 kcal of inositol.
10. The nutritional composition of claim 1, wherein the nutritional
composition comprises about 3.5 g/100 kcal to about 4.5 g/100 kcal
of the protein or protein equivalent.
11. The nutritional composition of claim 1, wherein the protein or
protein equivalent comprises intact proteins and hydrolyzed
proteins.
12. The nutritional composition of claim 1, wherein the protein or
protein equivalent comprises hydrolyzed proteins, and wherein the
degree of hydrolysis is from about 20% to about 80%.
13. The nutritional composition of claim 1, wherein the nutritional
composition is protein-free and the protein equivalent comprises
free amino acids.
14. The nutritional composition of claim 1, wherein the nutritional
composition comprises about 6 g/100 kcal to about 22 g/100 kcal of
the carbohydrate.
15. The nutritional composition of claim 1, wherein the
carbohydrate comprises a saccharide, a starch, and combinations
thereof.
16. The nutritional composition of claim 15, wherein the
nutritional composition comprises about 17 mg/100 kcal to about 37
mg/100 kcal of inositol.
17. The nutritional composition of claim 1 further comprising an
enriched lipid fraction derived from milk.
18. The nutritional composition of claim 17, wherein the enriched
lipid fraction comprises milk fat globules.
19. The nutritional composition of claim 1 further comprising a
pectin or gelatinized pectin.
20. The nutritional composition of claim 1, wherein the nutritional
composition comprises: about 2 g/100 kcal to about 7 g/100 kcal of
the fat or lipid; about 1 g/100 kcal to about 7 g/100 kcal of the
protein or protein equivalent; about 5 g/100 kcal to about 25 g/100
kcal of the carbohydrate; and about 12 mg/100 kcal to about 40
mg/100 kcal of inositol.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is a divisional application of, and claims
priority to, U.S. application Ser. No. 14/729,132, filed on 3 Jun.
2015, the disclosure of which is herein incorporated by reference
in its entirety.
BACKGROUND OF THE INVENTION
1. Field of the Invention
[0002] The present disclosure relates to nutritional compositions
that include inositol at levels found to provide neurological
benefits. More particularly, the disclosed nutritional compositions
include a fat, a carbohydrate, a protein or protein equivalent
source, and inositol, for improving neurological health and/or
preventing or protecting against the development of
neurodegenerative diseases. The nutritional compositions described
herein are suitable for administration to adult and pediatric
subjects.
2. Background
[0003] The nervous system is responsible for accumulating and
analyzing sensory input and coordinating the generation of the
appropriate functional response. The successful execution and
integration of these activities is dependent on the transmission of
neuronal action potentials, electrical signals required to generate
functional outputs. While it is the neuronal cell that is
responsible for the actual conduction of the signaling current, the
rate at which the signal travels is greatly enhanced by the
insulating properties of its glial-derived myelin sheath. In the
central nervous system (CNS), glial cells known as oligodendrocytes
are responsible for the formation of myelin. These terminally
differentiated cells arise from progenitors termed oligodendrocyte
precursor cells (OPCs). During development, OPCs are exposed to
proliferative signals as they migrate along axons throughout the
CNS. These developmental cues help ensure that the extent of OPC
proliferation is sufficient to generate the appropriate number of
oligodendrocytes to myelinate all relevant axonal segments. Once
the required number of precursor cells has been generated, the
differentiation process initiates followed by myelination.
[0004] Therefore, the impacts on the myelination process by brain
nutrients are integrated by three basic aspects: (1) the survival
and proliferation of oligodendritic projector cells (OPCs); (2) the
differentiation of OPCs into oligodendric cells (Oligo); and
myelination deposition.
[0005] Myelination and synapse development are very important for
neurological health. This is true in infants and children, for
brain development and to provide improvement in specific brain
function such as cognition, memory function, learning capacity,
social interaction skills, reduced anxiety, visual acuity, motor
skills and/or language skills. Likewise, improved myelination and
synapse development can be beneficial in adults, especially adults
with neurodegenerative diseases like Alzheimer's disease.
[0006] Myelination can be described as the process by which a fatty
layer, called myelin, accumulates around nerve cells (neurons), and
begins in infancy and continues through adulthood. Myelin
particularly forms around the long shaft, or axon, of neurons.
Myelination enables nerve cells to transmit information faster and
allows for more complex brain processes. Thus, the process is
vitally important to healthy central nervous system
functioning.
[0007] In the nervous system, a synapse is a structure that permits
a neuron to pass an electrical or chemical signal to another cell
(neural or otherwise). Thus, synapses are essential to neuronal
function: neurons are cells that are specialized to pass signals to
individual target cells, and synapses are the means by which they
do so. At a synapse, the plasma membrane of the signal-passing
neuron (the presynaptic neuron) comes into close apposition with
the membrane of the target (postsynaptic) cell. Both the
presynaptic and postsynaptic sites contain extensive arrays of
molecular machinery that link the two membranes together and carry
out the signaling process. Synapse development, or synaptogenesis,
is the formation of synapses between neurons in the nervous system.
Although it occurs throughout a healthy person's lifespan, an
explosion of synapse formation occurs during early brain
development, known as exuberant synaptogenesis.
[0008] Myelination begins in the brain stem and cerebellum before
birth, but is not completed in the frontal cortex until late in
adolescence. Breast feeding contributes to more rapid myelination
in the brain. Identification of nutrients that promote survival and
proliferation of oligodendrocytes represents a major unmet need.
Beyond normal development, white matter injury is one of the
leading causes of neurological disease in infants, especially in
infants born premature. In these cases, oligodendrocyte cell death
and a lack of developmental myelination represent leading factors,
resulting in aberrant neural circuit formation and nervous system
refinement.
[0009] Thus, it would be useful to provide nutritional compositions
that are able to improve myelination and synapse development in a
subject. In particular, it may be useful to provide improved
neurological health and function, including cognition, language
development and motor skills in early life in order to reduce or
prevent adult neurological diseases. It would also be useful to
combat neurodegenerative disease through improved myelination and
synapse development in adults.
[0010] Accordingly, the present disclosure provides a nutritional
composition including inositol as described herein. In some
embodiments, the nutritional composition also includes a fat or
lipid, carbohydrate and protein or protein equivalent source.
BRIEF SUMMARY OF THE INVENTION
[0011] Briefly, the present disclosure is directed, in an
embodiment, to a nutritional composition comprising exogenous
inositol, and to a method for providing improved neurological
health and function, including cognition, language development and
motor skills in early life in order to reduce or prevent adult
neurological diseases, in a pediatric subject, the method
comprising administering to the pediatric subject a nutritional
composition comprising inositol, a fat or lipid, a protein or
protein equivalent source and a carbohydrate. In some embodiments,
the nutritional composition can also include one or more long chain
polyunsaturated fatty acids (LCPUFAs) selected from the group
consisting of docosahexaenoic acid (DHA) and arachidonic acid
(ARA), phosphatidylethanolamines (PE), sphingomyelin (SPM),
alpha-lipoic acid (ALA), epigallocatechin gallate (EGCG),
sulforaphane, or combinations thereof, which may synergistically
combine with inositol to further improve neurological health and
development.
[0012] In certain embodiments, the nutritional composition further
comprises an enriched lipid fraction derived from milk. In some
embodiments the nutritional composition may include an enriched
lipid fraction derived from milk that includes milk fat globules.
The addition of the milk fat globules provides an enriched fat and
lipid source to the infant that may be more fully digested by a
pediatric subject.
[0013] In embodiments, the enriched lipid fraction and/or the milk
fat globules may include saturated fatty acids, trans-fatty acids,
monounsaturated fatty acids, polyunsaturated fatty acids,
cholesterol, odd-branched chain fatty acids "OBCFAs", branched
chain fatty acids "BCFAs", conjugated linoleic acid "CLA",
phospholipids, or milk fat globule membrane protein, and mixtures
thereof.
[0014] In one aspect, the disclosure provides a nutritional
composition for enhancing neurological health and development in a
subject, the nutritional composition comprising: a fat or lipid; a
protein or protein equivalent; a carbohydrate; and inositol,
wherein the inositol comprises exogenous inositol and inherent
inositol, and wherein a ratio of the exogenous inositol to the
inherent inositol is at least 75:25.
[0015] In some embodiments, the nutritional composition can further
comprise a long chain polyunsaturated fatty acid. In some
embodiments, the long chain polyunsaturated fatty acid can comprise
at least one of docosahexaenoic acid, arachidonic acid, and
combinations thereof In some embodiments, the long chain
polyunsaturated fatty acid can be present from about 5 mg/100 kcal
to about 75 mg/100 kcal.
[0016] In some embodiments, the nutritional composition can further
comprise docosahexaenoic acid, arachidonic acid,
phosphatidylethanolamines, sphingomyelin, alpha-lipoic acid,
epigallocatechin gallate, sulforaphane, or combinations
thereof.
[0017] In some embodiments, the nutritional composition can further
comprise about 10 mg/100 kcal to about 2500 mg/100 kcal of
lactoferrin.
[0018] In some embodiments, the nutritional composition can further
comprise a prebiotic composition comprising polydextrose and
galactooligosaccharides, wherein the prebiotic composition can
comprise at least 20% w/w polydextrose and galactooligosaccharides
and mixtures thereof.
[0019] In some embodiments, the nutritional composition is an
infant formula or a growing up milk.
[0020] In some embodiments, the nutritional composition can
comprise: no greater than about 7 g/100 kcal of the fat or lipid;
no greater than about 7 g/100 kcal of the protein or protein
equivalent; at least about 5 g/100 kcal of the carbohydrate; and at
least about 9 mg/100 kcal of inositol.
[0021] In some embodiments, the nutritional composition can
comprise about 3.5 g/100 kcal to about 4.5 g/100 kcal of the
protein or protein equivalent. In some embodiments, the protein or
protein equivalent can comprise intact proteins and hydrolyzed
proteins. In some embodiments, the protein or protein equivalent
can comprise hydrolyzed proteins, wherein the degree of hydrolysis
is from about 20% to about 80%.
[0022] In some embodiments, the nutritional composition is
protein-free and the protein equivalent comprises free amino
acids.
[0023] In some embodiments, the nutritional composition can
comprise about 6 g/100 kcal to about 22 g/100 kcal of the
carbohydrate. In some embodiments, the carbohydrate can comprise a
saccharide, a starch, and combinations thereof.
[0024] In some embodiments, the nutritional composition can
comprise about 17 mg/100 kcal to about 37 mg/100 kcal of
inositol.
[0025] In some embodiments, the nutritional composition can further
comprise an enriched lipid fraction derived from milk. In some
embodiments, the enriched lipid fraction can comprise milk fat
globules.
[0026] In some embodiments, the nutritional composition can further
comprise a pectin or gelatinized pectin.
[0027] In some embodiments, the nutritional composition can
comprise: about 2 g/100 kcal to about 7 g/100 kcal of the fat or
lipid; about 1 g/100 kcal to about 7 g/100 kcal of the protein or
protein equivalent; about 5 g/100 kcal to about 25 g/100 kcal of
the carbohydrate; and about 12 mg/100 kcal to about 40 mg/100 kca1
of inositol.
[0028] 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.
[0029] These and other objects, features and advantages of the
present invention will become more apparent upon reading the
following specification in conjunction with the accompanying
description, claims and drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
[0030] The accompanying Figures, which are incorporated in and
constitute a part of this specification, illustrate several aspects
described below. The patent or application file contains at least
one drawing executed in color. Copies of this patent or patent
application publication with color drawing(s) will be provided by
the Office upon request and payment of the necessary fee.
[0031] FIG. 1 illustrates a dose-response for inositol on purified
oligodendrogial cultures, resulting from the testing of Example
1.
[0032] FIG. 2 illustrates the OPCs, normalized to 40 .mu.M
resulting from the testing of Example 2.
[0033] FIG. 3 illustrates the Oligo Number, normalized to 40 .mu.M
resulting from the testing of Example 3.
[0034] FIG. 4 shows the dual-fluorescence labeling of OPCs and
oligodendrytes, as well as myelin deposition, resulting from the
testing of Example 4.
[0035] FIG. 5 illustrates a dose-response of inositol on myelin
extent.
[0036] FIGS. 6 and 7 illustrate the Density Bassoon and Density
Homer counts resulting from the testing of Example 6.
[0037] FIG. 8 illustrates the colocalization of synaptic sites
resulting from the testing of Example 6.
[0038] FIG. 9 illustrates the synaptic site sizes resulting from
the testing of Example 6.
[0039] FIG. 10 shows the effects of inositol on synaptic
development under the florescent microscopy resulting from the
testing of Example 6.
DETAILED DESCRIPTION OF THE INVENTION
[0040] To facilitate an understanding of the principles and
features of the various embodiments of the invention, various
illustrative embodiments are explained below. Although exemplary
embodiments of the invention are explained in detail, it is to be
understood that other embodiments are contemplated. Accordingly, it
is not intended that the invention is limited in its scope to the
details of construction and arrangement of components set forth in
the following description or examples. The invention is capable of
other embodiments and of being practiced or carried out in various
ways. Also, in describing the exemplary embodiments, specific
terminology will be resorted to for the sake of clarity.
[0041] It must also be noted that, as used in the specification and
the appended claims, the singular forms "a," "an" and "the" include
plural references unless the context clearly dictates otherwise.
For example, reference to a component is intended also to include
composition of a plurality of components. References to a
composition containing "a" constituent is intended to include other
constituents in addition to the one named. In other words, the
terms "a," "an," and "the" do not denote a limitation of quantity,
but rather denote the presence of "at least one" of the referenced
item.
[0042] As used herein, the term "and/or" may mean "and," it may
mean "or," it may mean "exclusive-or," it may mean "one," it may
mean "some, but not all," it may mean "neither," and/or it may mean
"both." The term "or" is intended to mean an inclusive "or."
[0043] Also, in describing the exemplary embodiments, terminology
will be resorted to for the sake of clarity. It is intended that
each term contemplates its broadest meaning as understood by those
skilled in the art and includes all technical equivalents which
operate in a similar manner to accomplish a similar purpose. It is
to be understood that embodiments of the disclosed technology may
be practiced without these specific details. In other instances,
well-known methods, structures, and techniques have not been shown
in detail in order not to obscure an understanding of this
description. References to "one embodiment," "an embodiment,"
"example embodiment," "some embodiments," "certain embodiments,"
"various embodiments," etc., indicate that the embodiment(s) of the
disclosed technology so described may include a particular feature,
structure, or characteristic, but not every embodiment necessarily
includes the particular feature, structure, or characteristic.
Further, repeated use of the phrase "in one embodiment" does not
necessarily refer to the same embodiment, although it may.
[0044] Ranges may be expressed herein as from "about" or
"approximately" or "substantially" one particular value and/or to
"about" or "approximately" or "substantially" another particular
value. When such a range is expressed, other exemplary embodiments
include from the one particular value and/or to the other
particular value. Further, the term "about" means within an
acceptable error range for the particular value as determined by
one of ordinary skill in the art, which will depend in part on how
the value is measured or determined, i.e., the limitations of the
measurement system. For example, "about" can mean within an
acceptable standard deviation, per the practice in the art.
Alternatively, "about" can mean a range of up to .+-.20%,
preferably up to .+-.10%, more preferably up to .+-.5%, and more
preferably still up to .+-.1% of a given value. Alternatively,
particularly with respect to biological systems or processes, the
term can mean within an order of magnitude, preferably within
2-fold, of a value. Where particular values are described in the
application and claims, unless otherwise stated, the term "about"
is implicit and in this context means within an acceptable error
range for the particular value. Throughout this disclosure, various
aspects of the invention can be presented in a range format. It
should be understood that the description in range format is merely
for convenience and brevity and should not be construed as an
inflexible limitation on the scope of the invention. Accordingly,
the description of a range should be considered to have
specifically disclosed all the possible subranges as well as
individual numerical values within that range. For example,
description of a range such as from 1 to 6 should be considered to
have specifically disclosed subranges such as from 1 to 3, from 1
to 4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6 etc., as
well as individual numbers within that range, for example, 1, 2,
2.7, 3, 4, 5, 5.3, and 6. This applies regardless of the breadth of
the range.
[0045] Similarly, as used herein, "substantially free" of
something, or "substantially pure", and like characterizations, can
include both being "at least substantially free" of something, or
"at least substantially pure", and being "completely free" of
something, or "completely pure".
[0046] By "comprising" or "containing" or "including" is meant that
at least the named compound, element, particle, or method step is
present in the composition or article or method, but does not
exclude the presence of other compounds, materials, particles,
method steps, even if the other such compounds, material,
particles, method steps have the same function as what is
named.
[0047] Throughout this description, various components may be
identified having specific values or parameters, however, these
items are provided as exemplary embodiments. Indeed, the exemplary
embodiments do not limit the various aspects and concepts of the
present invention as many comparable parameters, sizes, ranges,
and/or values may be implemented. The terms "first," "second," and
the like, "primary," "secondary," and the like, do not denote any
order, quantity, or importance, but rather are used to distinguish
one element from another.
[0048] It is noted that terms like "specifically," "preferably,"
"typically," "generally," and "often" are not utilized herein to
limit the scope of the claimed invention or to imply that certain
features are critical, essential, or even important to the
structure or function of the claimed invention. Rather, these terms
are merely intended to highlight alternative or additional features
that may or may not be utilized in a particular embodiment of the
present invention. It is also noted that terms like "substantially"
and "about" are utilized herein to represent the inherent degree of
uncertainty that may be attributed to any quantitative comparison,
value, measurement, or other representation.
[0049] The dimensions and values disclosed herein are not to be
understood as being strictly limited to the exact numerical values
recited. Instead, unless otherwise specified, each such dimension
is intended to mean both the recited value and a functionally
equivalent range surrounding that value. For example, a dimension
disclosed as "50 mm" is intended to mean "about 50 mm."
[0050] It is also to be understood that the mention of one or more
method steps does not preclude the presence of additional method
steps or intervening method steps between those steps expressly
identified. Similarly, it is also to be understood that the mention
of one or more components in a composition does not preclude the
presence of additional components than those expressly
identified.
[0051] The materials described hereinafter as making up the various
elements of the present invention are intended to be illustrative
and not restrictive. Many suitable materials that would perform the
same or a similar function as the materials described herein are
intended to be embraced within the scope of the invention. Such
other materials not described herein can include, but are not
limited to, materials that are developed after the time of the
development of the invention, for example. Any dimensions listed in
the various drawings are for illustrative purposes only and are not
intended to be limiting. Other dimensions and proportions are
contemplated and intended to be included within the scope of the
invention.
[0052] Reference now will be made in detail to the embodiments of
the present disclosure, one or more examples of which are set forth
hereinbelow. 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.
[0053] 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 obvious
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.
[0054] The present disclosure relates generally to nutritional
compositions that are suitable for administration to a pediatric
subject. Additionally, the disclosure relates to methods for
improving neurological health and development in children and
adults via administration of the nutritional composition(s)
disclosed herein.
[0055] "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-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.
[0056] The term "enteral" means deliverable through or within the
gastrointestinal, or digestive, tract. "Enteral administration"
includes oral feeding, intragastric feeding, transpyloric
administration, or any other administration into the digestive
tract. "Administration" is broader than "enteral administration"
and includes parenteral administration or any other route of
administration by which a substance is taken into a subject's
body.
[0057] "Pediatric subject" means a human no greater 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 full
term) and/or children, as described below.
[0058] "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, extremely low
birth weight infants and preterm infants. "Preterm" means an infant
born before the end of the 37th week of gestation. "Late preterm"
means an infant from between the 34th week and the 36th week of
gestation. "Full term" means an infant born after the end of the
37th week of gestation. "Low birth weight infant" means an infant
born weighing less than 2500 grams (approximately 5 lbs, 8 ounces).
"Very low birth weight infant" means an infant born weighing less
than 1500 grams (approximately 3 lbs, 4 ounces). "Extremely low
birth weight infant" means an infant born weighing less than 100
grams (approximately 2 lbs, 3 ounces).
[0059] "Child" means a subject ranging in age from 12 months to 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.
[0060] "Children's nutritional product" refers to a composition
that satisfies at least a portion of the nutrient requirements of a
child. A growing-up milk is an example of a children's nutritional
product.
[0061] 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 methods for
determining amino nitrogen content, while the total nitrogen
component is determined by the Tecator Kjeldahl method, all of
which are well known methods to one of ordinary skill in the
analytical chemistry art.
[0062] The term "partially hydrolyzed" means having a degree of
hydrolysis which is greater than 0% but less than about 50%.
[0063] The term "extensively hydrolyzed" means having a degree of
hydrolysis which is greater than or equal to about 50%.
[0064] The term "protein-free" means containing no measurable
amount of 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.
[0065] "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.
These regulations define macronutrient, vitamin, mineral, and other
ingredient levels in an effort to simulate the nutritional and
other properties of human breast milk.
[0066] 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.
[0067] "Milk-based" means comprising at least one component that
has been drawn or extracted from the mammary gland of a mammal. In
some embodiments, a milk-based nutritional composition comprises
components of milk that are derived from domesticated ungulates,
ruminants or other mammals or any combination thereof. Moreover, in
some embodiments, milk-based means comprising bovine casein, whey,
lactose, or any combination thereof. Further, "milk-based
nutritional composition" may refer to any composition comprising
any milk-derived or milk-based product known in the art.
[0068] "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.
[0069] "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.
[0070] "Fat globule" refers to a small mass of fat surrounded by
phospholipids and other membrane and/or serum proteins, where the
fat itself can be a combination of any vegetable or animal fat.
[0071] "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.
[0072] Therefore, a nutritional composition that is "nutritionally
complete" for a preterm infant will, by definition, provide
qualitatively and quantitatively adequate amounts of carbohydrates,
lipids, essential fatty acids, proteins, essential amino acids,
conditionally essential amino acids, vitamins, minerals, and energy
required for growth of the preterm infant.
[0073] 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.
[0074] 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.
[0075] As applied to nutrients, the term "essential" refers to any
nutrient that cannot be synthesized by the body in amounts
sufficient for normal growth and to maintain health and that,
therefore, must be supplied by the diet. The term "conditionally
essential" as applied to nutrients means that the nutrient must be
supplied by the diet under conditions when adequate amounts of the
precursor compound is unavailable to the body for endogenous
synthesis to occur.
[0076] "Probiotic" means a microorganism with low or no
pathogenicity that exerts a beneficial effect on the health of the
host.
[0077] The term "inactivated probiotic" means a probiotic wherein
the metabolic activity or reproductive ability of the referenced
probiotic has been reduced or destroyed. The "inactivated
probiotic" does, however, still retain, at the cellular level, its
cell structure or other structure associated with the cell, for
example exopolysaccharide and at least a portion its biological
glycol-protein and DNA/RNA structure. As used herein, the term
"inactivated" is synonymous with "non-viable".
[0078] "Prebiotic" means a non-digestible food ingredient that
beneficially affects the host by selectively stimulating the growth
and/or activity of one or a limited number of bacteria in the
digestive tract that can improve the health of the host.
[0079] "Inherent inositol", "endogenous inositol" or "inositol from
endogenous sources" each refer to inositol present in the
composition that is not added as such, but is present in other
components or ingredients of the composition; the inositol is
naturally present in such other components. Contrariwise,
"exogenous" inositol is inositol which is intentionally included in
the nutritional composition of the present disclosure itself,
rather than as an element of another component.
[0080] "Branched Chain Fatty Acid" ("BCFA") means a fatty acid
containing a carbon constituent branched off the carbon chain.
Typically the branch is an alkyl branch, especially a methyl group,
but ethyl and propyl branches are also known. The addition of the
methyl branch lowers the melting point compared with the equivalent
straight chain fatty acid. This includes branched chain fatty acids
with an even number of carbon atoms in the carbon chain. Examples
of these can be isomers of tetradecanoic acid, hexadecanoic
acid.
[0081] "Odd- and Branched-Chain Fatty Acid" ("OBCFA") is a subset
of BCFA that has an odd number of carbon atoms and have one or more
alkyl branches on the carbon chain. The main odd- and
branched-chain fatty acids found in bovine milk include, but are
not limited to, the isomers of tetradecanoic acid, pentadecanoic
acid, hexadecanoic acid, and heptadecanoic acid. For the purposes
of this disclosure, the term "BCFA" includes both branched-chain
fatty acids and odd-and-branched chain fatty acids.
[0082] "Trans-fatty acid" means an unsaturated fat with a
trans-isomer. Trans-fats may be monounsaturated or polyunsaturated.
Trans refers to the arrangement of the two hydrogen atoms bonded to
the carbon atoms involved in a double bond. In the trans
arrangement, the hydrogens are on opposite sides of the bond. Thus
a trans-fatty acid is a lipid molecule that contains one or more
double bonds in trans geometric configuration.
[0083] "Phospholipids" means an organic molecule that contains a
diglyceride, a phosphate group and a simple organic molecule.
Examples of phospholipids include but are not limited to,
phosphatidic acid, phosphatidylethanolamine, phosphatidylcholine,
phosphatidylserine, phsphatidylinositol, phosphatidylinositol
phosphate, phosphatidylinositol biphosphate and
phosphatidylinositol triphosphate, ceramide phosphorylcholine,
ceramide phosphorylethanolamine and ceramide phosphorylglycerol.
This definition further includes sphigolipids, glycolipids, and
gangliosides.
[0084] "Phytonutrient" means a chemical compound that occurs
naturally in plants. Phytonutrients may be included in any
plant-derived substance or extract. The term "phytonutrient(s)"
encompasses several broad categories of compounds produced by
plants, such as, for example, polyphenolic compounds, anthocyanins,
proanthocyanidins, and flavan-3-ols (i.e. catechins, epicatechins),
and may be derived from, for example, fruit, seed or tea extracts.
Further, the term phytonutrient includes all carotenoids,
phytosterols, thiols, and other plant-derived compounds. Moreover,
as a skilled artisan will understand, plant extracts may include
phytonutrients, such as polyphenols, in addition to protein, fiber
or other plant-derived components. Thus, for example, apple or
grape seed extract(s) may include beneficial phytonutrient
components, such as polyphenols, in addition to other plant-derived
substances. ".beta.-glucan" means all .beta.-glucan, including
specific types of .beta.-glucan, such as .beta.-1,3-glucan or
.beta.-1,3;1,6-glucan. Moreover, .beta.-1,3;1,6-glucan is a type of
.beta.-1,3-glucan. Therefore, the term ".beta.-1,3-glucan" includes
.beta.-1,3;1,6-glucan.
[0085] "Pectin" means any naturally-occurring oligosaccharide or
polysaccharide that comprises galacturonic acid that may be found
in the cell wall of a plant. Different varieties and grades of
pectin having varied physical and chemical properties are known in
the art. Indeed, the structure of pectin can vary significantly
between plants, between tissues, and even within a single cell
wall. Generally, pectin is made up of negatively charged acidic
sugars (galacturonic acid), and some of the acidic groups are in
the form of a methyl ester group. The degree of esterification of
pectin is a measure of the percentage of the carboxyl groups
attached to the galactopyranosyluronic acid units that are
esterified with methanol.
[0086] Pectin having a degree of esterification of less than 50%
(i.e., less than 50% of the carboxyl groups are methylated to form
methyl ester groups) are classified as low-ester, low methoxyl, or
low methylated ("LM") pectins, while those having a degree of
esterification of 50% or greater (i.e., more than 50% of the
carboxyl groups are methylated) are classified as high-ester, high
methoxyl or high methylated ("HM") pectins. Very low ("VL")
pectins, a subset of low methylated pectins, have a degree of
esterification that is less than approximately 15%.
[0087] As used herein, "lactoferrin from a non-human source" means
lactoferrin which is produced by or obtained from a source other
than human breast milk. For example, lactoferrin for use in the
present disclosure includes human lactoferrin produced by a
genetically modified organism as well as non-human lactoferrin. The
term "organism", as used herein, refers to any contiguous living
system, such as animal, plant, fungus or micro-organism.
[0088] As used herein, "non-human lactoferrin" means lactoferrin
that has an amino acid sequence that is different than the amino
acid sequence of human lactoferrin.
[0089] "Pathogen" means an organism that causes a disease state or
pathological syndrome. Examples of pathogens may include bacteria,
viruses, parasites, fungi, microbes or combination(s) thereof.
[0090] "Modulate" or "modulating" means exerting a modifying,
controlling and/or regulating influence. In some embodiments, the
term "modulating" means exhibiting an increasing or stimulatory
effect on the level/amount of a particular component. In other
embodiments, "modulating" means exhibiting a decreasing or
inhibitory effect on the level/amount of a particular
component.
[0091] All percentages, parts and ratios as used herein are by
weight of the total formulation, unless otherwise specified.
[0092] All amounts specified as administered "per day" may be
delivered in one unit dose, in a single serving or in two or more
doses or servings administered over the course of a 24 hour
period.
[0093] 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.
[0094] 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.
[0095] 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.
[0096] 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.
[0097] 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.
[0098] The present disclosure is directed to nutritional
compositions comprising inositol, to uses thereof, and to methods
comprising administration of those nutritional compositions to a
pediatric or adult subject. The nutritional compositions of the
present disclosure support and improve neurological health and
development.
[0099] Inositol is transported across the blood-brain barrier by
simple diffusion and a stereospecific saturation transport system.
Moreover, the brain can take up inositol after exogenous
administration. It has thus been found that oral administration of
inositol can engender enhance neurological conditions for brain
benefits.
[0100] It has been found that nutritional supplementation of
inositol represents a feasible and effective approach to promote
oligodendrocyte survival and proliferation in a dose dependent
manner, resulting in a consistent increase in the number of
oligodendrocyte precursor cells. Nutritional supplementation with
inositol provides benefits for enhanced developmental myelination
by which it translates into a fundamental benefit for brain
development. Given the importance of functional myelination,
nutritional supplementation of inositol is beneficial to pediatric
and adult subjects by enhancing brain development and health.
Because the nature and characteristics of inositol allow it to
cross the blood brain barrier, inositol can be considered a novel
brain nutrient, synergizing with other nutrients to provide
comprehensive brain development benefits. Moreover, the positive
effects on enhanced developmental myelination from inositol can be
beneficial for preterm infants as well as those diagnosed with
white matter diseases (such as cerebral palsy and periventricular
leukomalacia). Inositol can also be beneficial in other situations
where myelination can be an issue, such as with patients having
multiple sclerosis and in post radiation supplementation for
promotion of recovery of OPCs. Moreover, the sweet taste of
inositol provides further advantages in terms of palatability to
consumers, especially infants and children.
[0101] In certain embodiments, inositol is present in the
nutritional compositions of the present disclosure at a level of at
least about 9 mg/100 kcal; in other embodiments, inositol should be
present at a level of no greater than about 42 mg/100 kcal. In
still other embodiments, the nutritional composition comprises
inositol at a level of about 12 mg/100 kcal to about 40 mg/100
kcal. In a further embodiment, inositol is present in the
nutritional composition at a level of about 17 mg/100 kcal to about
37 mg/100 kcal. Moreover, inositol can be present as exogenous
inositol or inherent inositol. In embodiments, a major fraction of
the inositol (i.e., at least 40%) is exogenous inositol. In certain
embodiments, the ratio of exogenous to inherent inositol is at
least 50:50; in other embodiments, the ratio of exogenous to
inherent inositol is at least 65:35. In still other embodiments,
the ratio of exogenous inositol to inherent inositol in the
disclosed nutritional composition is at least 75:25.
[0102] In some embodiments, the nutritional composition(s) of the
disclosure may also comprise at least one protein or protein
equivalent source, which 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.
[0103] In some embodiments, 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 hydrolyzed proteins. In certain embodiments, the proteins may
be partially hydrolyzed or extensively hydrolyzed. In still other
embodiments, the protein equivalent source comprises amino acids.
In yet another embodiment, the protein source may be supplemented
with glutamine-containing peptides. In another embodiment, the
protein component comprises extensively hydrolyzed protein. In
still another embodiment, the protein component of the nutritional
composition consists essentially of extensively hydrolyzed protein
in order to minimize the occurrence of food allergy. In yet another
embodiment, the protein source may be supplemented with
glutamine-containing peptides.
[0104] Accordingly, in some embodiments, the protein component of
the nutritional composition comprises either partially or
extensively hydrolyzed protein, such as protein from cow's
milk.
[0105] The hydrolyzed proteins may be treated with enzymes to break
down some or most of the proteins that cause adverse symptoms with
the goal of reducing allergic reactions, intolerance, and
sensitization. Moreover, the proteins may be hydrolyzed by any
method known in the art.
[0106] The terms "protein hydrolysates" or "hydrolyzed protein" are
used interchangeably herein and refer to hydrolyzed proteins,
wherein the degree of hydrolysis is may be from about 20% to about
80%, or from about 30% to about 80%, or even from about 40% to
about 60%.
[0107] 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).
[0108] 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, 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 formulation may be hypoallergenic.
[0109] In an embodiment, the protein source comprises from about
40% to about 85% whey protein and from about 15% to about 60%
casein.
[0110] In some embodiments, the nutritional composition comprises
no greater than 7 g/100 kcal, and, in certain embodiments, between
about 1 g and about 7 g of a protein and/or protein equivalent
source per 100 kcal. In other embodiments, the nutritional
composition comprises between about 3.5 g and about 4.5 g of
protein or protein equivalent per 100 kcal.
[0111] In some embodiments, the nutritional composition comprises
at least one 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 the additional carbohydrate component in the
nutritional composition typically can be greater than 5 g/100 kcal;
in some embodiments, it 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 desirable for inclusion in the
nutritional composition due to their easy digestibility.
Specifically, hydrolyzed carbohydrates are less likely to contain
allergenic epitopes.
[0112] 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.
[0113] In one particular embodiment, the carbohydrate component of
the nutritional composition is comprised of 100 % lactose. In
another embodiment, the additional carbohydrate component comprises
between about 0% and 60% lactose. In another embodiment, the
carbohydrate component comprises between about 15% and 55% lactose.
In yet another embodiment, the carbohydrate component comprises
between about 20% and 30% lactose. In these embodiments, the
remaining source of carbohydrates may be any carbohydrate known in
the art. In an embodiment, the carbohydrate component comprises
about 25% lactose and about 75% corn syrup solids.
[0114] In some embodiments, the carbohydrate may comprise at least
one starch or starch component. A starch is a carbohydrate composed
of two distinct polymer fractions: amylose and amylopectin. Amylose
is the linear fraction consisting of .alpha.-1,4 linked glucose
units. Amylopectin has the same structure as amylose, but some of
the glucose units are combined in an .alpha.-1,6 linkage, giving
rise to a branched structure. Starches generally contain 17-24%
amylose and from 76-83% amylopectin. Yet special genetic varieties
of plants have been developed that produce starch with unusual
amylose to amylopectin ratios. Some plants produce starch that is
free of amylose. These mutants produce starch granules in the
endosperm and pollen that stain red with iodine and that contain
nearly 100 % amylopectin. Predominant among such amylopectin
producing plants are waxy corn, waxy sorghum and waxy rice
starch.
[0115] The performance of starches under conditions of heat, shear
and acid may be modified or improved by chemical modifications.
Modifications are usually attained by introduction of substituent
chemical groups. For example, viscosity at high temperatures or
high shear can be increased or stabilized by cross-linking with di-
or polyfunctional reagents, such as phosphorus oxychloride.
[0116] In some instances, the nutritional compositions of the
present disclosure comprise at least one starch that is gelatinized
or pregelatinized. As is known in the art, gelatinization occurs
when polymer molecules interact over a portion of their length to
form a network that entraps solvent and/or solute molecules.
Moreover, gels form when pectin molecules lose some water of
hydration owing to competitive hydration of cosolute molecules.
Factors that influence the occurrence of gelation include pH,
concentration of cosolutes, concentration and type of cations,
temperature and pectin concentration. Notably, LM pectin will gel
only in the presence of divalent cations, such as calcium ions. And
among LM pectins, those with the lowest degree of esterification
have the highest gelling temperatures and the greatest need for
divalent cations for crossbridging.
[0117] Meanwhile, pregelatinization of starch is a process of
precooking starch to produce material that hydrates and swells in
cold water. The precooked starch is then dried, for example by drum
drying or spray drying. Moreover the starch of the present
disclosure can be chemically modified to further extend the range
of its finished properties. The nutritional compositions of the
present disclosure may comprise at least one pregelatinized
starch.
[0118] Native starch granules are insoluble in water, but, when
heated in water, native starch granules begin to swell when
sufficient heat energy is present to overcome the bonding forces of
the starch molecules. With continued heating, the granule swells to
many times its original volume. The friction between these swollen
granules is the major factor that contributes to starch paste
viscosity.
[0119] The nutritional composition of the present disclosure may
comprise native or modified starches, such as, for example, waxy
corn starch, waxy rice starch, corn starch, rice starch, potato
starch, tapioca starch, wheat starch or any mixture thereof.
Generally, common corn starch comprises about 25% amylose, while
waxy corn starch is almost totally made up of amylopectin.
Meanwhile, potato starch generally comprises about 20% amylose,
rice starch comprises an amylose:amylopectin ratio of about 20:80,
and waxy rice starch comprises only about 2% amylose. Further,
tapioca starch generally comprises about 15% to about 18% amylose,
and wheat starch has an amylose content of around 25%.
[0120] In some embodiments, the nutritional composition comprises
gelatinized and/or pre-gelatinized waxy corn starch. In other
embodiments, the nutritional composition comprises gelatinized
and/or pre-gelatinized tapioca starch. Other gelatinized or
pre-gelatinized starches, such as rice starch or potato starch may
also be used.
[0121] Suitable fats or lipids for use in the nutritional
composition of the present disclosure may be any known or used in
the art, including but 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;
[0122] vegetable and plant oils, such as corn oil, canola oil,
sunflower oil, soybean oil, palmolein, 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.
[0123] The amount of lipids or fats is, in one embodiment, no
greater than about 7 g/100 kcal; in some embodiments, the lipid or
fat is present at a level of from about 2 to about 7 g/100
kcal.
[0124] The nutritional composition may also contain one or more
prebiotics (also referred to as a prebiotic component) in certain
embodiments. Prebiotics exert health benefits, which 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.
[0125] More specifically, prebiotics useful in the present
disclosure may include polydextrose (PDX), polydextrose powder,
lactulose, lactosucrose, raffinose, gluco-oligosaccharide, inulin,
fructo-oligosaccharide (FOS), isomalto-oligosaccharide, soybean
oligosaccharides, lactosucrose, xylo-oligosaccharide (XOS),
chito-oligosaccharide, manno-oligosaccharide,
aribino-oligosaccharide, siallyl-oligosaccharide,
fuco-oligosaccharide, galacto-oligosaccharides (GOS) and
gentio-oligosaccharides.
[0126] In an embodiment, the total amount of prebiotics present in
the nutritional composition may be from about 1.0 g/L to about 10.
g/L of the composition. More preferably, the total amount of
prebiotics present in the nutritional composition may be from about
2.0 g/L and about 8.0 g/L of the composition. In some embodiments,
the total amount of prebiotics present in the nutritional
composition may be from about 0.01 g/100 kcal to about 1.5 g/100
kcal. In certain embodiments, the total amount of prebiotics
present in the nutritional composition may be from about 0.15 g/100
kcal to about 1.5 g/100 kcal. Moreover, the nutritional composition
may comprise a prebiotic component comprising PDX. In some
embodiments, the prebiotic component comprises at least 20% w/w
PDX, GOS or a mixture thereof.
[0127] The amount of PDX in the nutritional composition may, in an
embodiment, be within the range of from about 0.015 g/100 kcal to
about 1.5 g/100 kcal. In another embodiment, the amount of
polydextrose is within the range of from about 0.2 g/100 kcal to
about 0.6 g/100 kcal. In some embodiments, PDX may be included in
the nutritional composition in an amount sufficient to provide
between about 1.0 g/L and 10. g/L. In another embodiment, the
nutritional composition contains an amount of PDX that is between
about 2.0 g/L and 8.0 g/L. And in still other embodiments, the
amount of PDX in the nutritional composition may be from about 0.05
g/100 kcal to about 1.5 g/100 kcal.
[0128] The prebiotic component also comprises GOS in some
embodiments. The amount of GOS in the nutritional composition may,
in an embodiment, be from about 0.015 g/100 kcal to about 1.0 g/100
kcal. In another embodiment, the amount of GOS in the nutritional
composition may be from about 0.2 g/100 kcal to about 0.5 g/100
kcal.
[0129] In a particular embodiment of the present disclosure, PDX is
administered in combination with GOS.
[0130] In a particular embodiment, GOS and PDX are supplemented
into the nutritional composition in a total amount of at least
about 0.015 g/100 kcal or about 0.015 g/100 kcal to about 1.5
mg/100 kcal. In some embodiments, the nutritional composition may
comprise GOS and PDX in a total amount of from about 0.1 to about
1.0 mg/100 kcal.
[0131] Lactoferrin can also be included in some embodiments of the
nutritional composition of the present disclosure. Lactoferrins are
single chain polypeptides of about 80 kD containing 1-4 glycans,
depending on the species. The 3-D structures of lactoferrin of
different species are very similar, but not identical. Each
lactoferrin comprises two homologous lobes, called the N- and
G-lobes, referring to the N-terminal and C-terminal part of the
molecule, respectively. Each lobe further consists of two sub-lobes
or domains, which form a cleft where the ferric ion (Fe.sup.3+) is
tightly bound in synergistic cooperation with a (bi)carbonate
anion. These domains are called N1, N2, C1 and C2, respectively.
The N-terminus of lactoferrin has strong cationic peptide regions
that are responsible for a number of important binding
characteristics. Lactoferrin has a very high isoelectric point
(.sup..about.pI 9) and its cationic nature plays a major role in
its ability to defend against bacterial, viral, and fungal
pathogens. There are several clusters of cationic amino acids
residues within the N-terminal region of lactoferrin mediating the
biological activities of lactoferrin against a wide range of
microorganisms. For instance, the N-terminal residues 1-47 of human
lactoferrin (1-48 of bovine lactoferrin) are critical to the
iron-independent biological activities of lactoferrin. In human
lactoferrin, residues 2 to 5 (RRRR) and 28 to 31 (RKVR) are
arginine-rich cationic domains in the N-terminus especially
critical to the antimicrobial activities of lactoferrin. A similar
region in the N-terminus is found in bovine lactoferrin (residues
17 to 42; FKCRRWQWRMKKLGAPSITCVRRAFA).
[0132] Lactoferrins from different host species may vary in their
amino acid sequences though commonly possess a relatively high
isoelectric point with positively charged amino acids at the end
terminal region of the internal lobe. Suitable non-human
lactoferrins for use in the present disclosure include, but are not
limited to, those having at least 48% homology with the amino acid
sequence of human lactoferrin. For instance, bovine lactoferrin
("bLF") has an amino acid composition which has about 70% sequence
homology to that of human lactoferrin. In some embodiments, the
non-human lactoferrin has at least 55% homology with human
lactoferrin and in some embodiments, at least 65% homology.
Non-human lactoferrins acceptable for use in the present disclosure
include, without limitation, bLF, porcine lactoferrin, equine
lactoferrin, buffalo lactoferrin, goat lactoferrin, murine
lactoferrin and camel lactoferrin.
[0133] In one embodiment, lactoferrin is present in the nutritional
composition in an amount of at least about 15 mg/100 kCal. In
certain embodiments, the nutritional composition may include
between about 15 and about 300 mg lactoferrin per 100 kCal. In
another embodiment, where the nutritional composition is an infant
formula, the nutritional composition may comprise lactoferrin in an
amount of from about 60 mg to about 150 mg lactoferrin per 100
kCal; in yet another embodiment, the nutritional composition may
comprise about 60 mg to about 100 mg lactoferrin per 100 kCal.
[0134] In some embodiments, the nutritional composition can include
lactoferrin in the quantities of from about 0.5 mg to about 1.5 mg
per milliliter of formula. In nutritional compositions replacing
human milk, lactoferrin may be present in quantities of from about
0.6 mg to about 1.3 mg per milliliter of formula. In certain
embodiments, the nutritional composition may comprise between about
0.1 and about 2 grams lactoferrin per liter. In some embodiments,
the nutritional composition includes between about 0.6 and about
1.5 grams lactoferrin per liter of formula.
[0135] The bLF that is used in certain embodiments may be any bLF
isolated from whole milk and/or having a low somatic cell count,
wherein "low somatic cell count" refers to a somatic cell count
less than 2500,000 cells/mL. By way of example, suitable bLF is
available from Tatua Co-operative Dairy Co. Ltd., in Morrinsville,
New Zealand, from FrieslandCampina Domo in Amersfoort, Netherlands
or from Fonterra Co-Operative Group Limited in Auckland, New
Zealand.
[0136] Lactoferrin for use in the present disclosure may be, for
example, isolated from the milk of a non-human animal or produced
by a genetically modified organism. For example, in U.S. Pat. No.
4,791,193, incorporated by reference herein in its entirety,
Okonogi et al. discloses a process for producing bovine lactoferrin
in high purity. Generally, the process as disclosed includes three
steps. Raw milk material is first contacted with a weakly acidic
cationic exchanger to absorb lactoferrin followed by the second
step where washing takes place to remove nonabsorbed substances. A
desorbing step follows where lactoferrin is removed to produce
purified bovine lactoferrin. Other methods may include steps as
described in U.S. Pat. Nos. 7,368,141, 5,849,885, 5,919,913 and
5,861,491, the disclosures of which are all incorporated by
reference in their entirety.
[0137] In certain embodiments, lactoferrin utilized in the present
disclosure may be provided by an expanded bed absorption ("EBA")
process for isolating proteins from milk sources. EBA, also
sometimes called stabilized fluid bed adsorption, is a process for
isolating a milk protein, such as lactoferrin, from a milk source
comprises establishing an expanded bed adsorption column comprising
a particulate matrix, applying a milk source to the matrix, and
eluting the lactoferrin from the matrix with an elution buffer
comprising about 0.3 to about 20 M sodium chloride. Any mammalian
milk source may be used in the present processes, although in
particular embodiments, the milk source is a bovine milk source.
The milk source comprises, in some embodiments, whole milk, reduced
fat milk, skim milk, whey, casein, or mixtures thereof.
[0138] In particular embodiments, the target protein is
lactoferrin, though other milk proteins, such as lactoperoxidases
or lactalbumins, also may be isolated. In some embodiments, the
process comprises the steps of establishing an expanded bed
adsorption column comprising a particulate matrix, applying a milk
source to the matrix, and eluting the lactoferrin from the matrix
with about 0.3 to about 2.0M sodium chloride. In other embodiments,
the lactoferrin is eluted with about 0.5 to about 1.0 M sodium
chloride, while in further embodiments, the lactoferrin is eluted
with about 0.7 to about 0.9 M sodium chloride.
[0139] The expanded bed adsorption (EBA) column can be any known in
the art, such as those described in U.S. Pat. Nos. 7,812,138,
6,620,326, and 6,977,046, the disclosures of which are hereby
incorporated by reference herein. In some embodiments, a milk
source is applied to the column in an expanded mode, and the
elution is performed in either expanded or packed mode. In
particular embodiments, the elution is performed in an expanded
mode. For example, the expansion ratio in the expanded mode may be
about 1 to about 3, or about 1.3 to about 1.7. EBA technology is
further described in international published application nos. WO
92/00799, WO 02/18237, WO 97/17132, which are hereby incorporated
by reference in their entireties.
[0140] The isoelectric point of lactoferrin is approximately 8.9.
Prior EBA methods of isolating lactoferrin use 200 mM sodium
hydroxide as an elution buffer. Thus, the pH of the system rises to
over 12, and the structure and bioactivity of lactoferrin may be
comprised, by irreversible structural changes. It has now been
discovered that a sodium chloride solution can be used as an
elution buffer in the isolation of lactoferrin from the EBA matrix.
In certain embodiments, the sodium chloride has a concentration of
about 0.3 M to about 2.0 M. In other embodiments, the lactoferrin
elution buffer has a sodium chloride concentration of about 0.3 M
to about 1.5 M, or about 0.5 m to about 1.0 M.
[0141] The nutritional composition of the disclosure can also
contain a source of LCPUFAs in certain embodiments; especially a
source of LCPUFAs that comprises DHA. Other suitable LCPUFAs
include, but are not limited to, .alpha.-linoleic acid,
.gamma.-linoleic acid, linoleic acid, linolenic acid,
eicosapentaenoic acid (EPA) and ARA. Indeed, DHA and/or ARA may act
synergistically with inositol to further improve neurological
health and development.
[0142] In an 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.
[0143] The amount of long chain polyunsaturated fatty acid 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.
[0144] The nutritional composition may be supplemented with oils
containing DHA and/or ARA using standard techniques known in the
art. For example, DHA and ARA may be added to the composition by
replacing an equivalent amount of an oil, such as high oleic
sunflower oil, normally present in the composition. As another
example, the oils containing DHA and ARA may be added to the
composition by replacing an equivalent amount of the rest of the
overall fat blend normally present in the composition without DHA
and ARA.
[0145] If utilized, the source of DHA and/or ARA may be any source
known in the art such as marine oil, fish oil, single cell oil, egg
yolk lipid, and brain lipid. In some embodiments, the DHA and ARA
are sourced from single cell Martek oils, DHASCO.RTM. and
ARASCO.RTM., or variations thereof. 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.
[0146] In an embodiment, sources of DHA and ARA are single cell
oils as taught in U.S. Pat. Nos. 5,374,567; 5,550,156; and
5,397,591, the disclosures of which are incorporated herein in
their entirety by reference. However, the present disclosure is not
limited to only such oils.
[0147] In some embodiments the nutritional composition may include
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. In some embodiments the nutritional
composition may include an enriched lipid fraction derived from
milk that contains milk fat globules.
[0148] In certain embodiments, the addition of the enriched lipid
fraction or the enriched lipid fraction including milk fat globules
may provide a source of saturated fatty acids, trans-fatty acids,
monounsaturated fatty acids, polyunsaturated fatty acids, OBCFAs,
BCFAs, CLA, cholesterol, phospholipids, and/or milk fat globule
membrane proteins to the nutritional composition.
[0149] The milk fat globules may have an average diameter
(volume-surface area average diameter) of at least about 2 .mu.m.
In some embodiments, the average diameter is in the range of from
about 2 .mu.m to about 13 .mu.m. In other embodiments, the milk fat
globules may range from about 2.5 .mu.m to about 10 .mu.m. Still in
other embodiments, the milk fat globules may range in average
diameter from about 3 .mu.m to about 6 .mu.m. The specific surface
area of the globules is, in certain embodiments, less than 3.5
m.sup.2/g, and in other embodiments is between about 0.9 m.sup.2/g
to about 3 m.sup.2/g. Without being bound by any particular theory,
it is believed that milk fat globules of the aforementioned sizes
are more accessible to lipases therefore leading to better
digestion lipid digestion.
[0150] In some embodiments the enriched lipid fraction and/or milk
fat globules contain saturated fatty acids. The saturated fatty
acids may be present in a concentration from about 0.1 g/100 kcal
to about 8.0 g/100 kcal. In certain embodiments the saturated fatty
acids may be present from about 0.5 g/100 kcal to about 2.0 g/100
kcal. In still other embodiments the saturated fatty acids may be
present from about 3.5 g/100 kcal to about 6.9 g/100 kcal.
[0151] Examples of saturated fatty acids suitable for inclusion
include, but are not limited to, butyric, valeric, caproic,
caprylic, decanoic, lauric, myristic, palmitic, steraic, arachidic,
behenic, alignoceric, tetradecanoic, hexadecanoic, palmitic, and
octadecanoic acid, and/or combinations and mixtures thereof.
[0152] Additionally, the enriched lipid fraction and/or milk fat
globules may comprise, in some embodiments, lauric acid. Lauric
acid, also known as dodecanoic acid, is a saturated fatty acid with
a 12-carbon atom chain and is believed to be one of the main
antiviral and antibacterial substances currently found in human
breast milk. The milk fat globules may be enriched with
triglycerides containing lauric acid at either the Sn-1, Sn-2
and/or Sn-3 positions. Without being bound by any particular
theory, it is believed that when the enriched lipid fraction is
ingested, the mouth lingual lipase and pancreatic lipase will
hydrolyze the triglycerides to a mixture of glycerides including
mono-lauric and free lauric acid.
[0153] The concentration of lauric acid in the globules varies from
80 mg/100 ml to 800 mg/100 ml. The concentration of monolauryl in
the globules can be in the range of 20 mg/100 ml to 300 mg/100 ml
feed. In some embodiments, the range is 60 mg/100 ml to 130 mg/100
ml.
[0154] The enriched lipid fraction and/or milk fat globules may
contain trans-fatty acids in certain embodiments. The trans-fatty
acids included in the milk fat globules may be monounsaturated or
polyunsaturated trans-fatty acids. In some embodiments the
trans-fatty acids may be present in an amount from about 0.2 g/100
kcal to about 7.0 g/100 kcal. In other embodiments the trans-fatty
acids may be present in an amount from about 3.4 g/100 kcal to
about 5.2 g/100 kcal. In yet other embodiments the trans-fatty
acids may be present from about 1.2 g/100 kcal to about 4.3 g/100
kcal.
[0155] Examples of trans-fatty acids for inclusion include, but are
not limited to, vaccenic, or elaidic acid, and mixtures thererof.
Moreover, when consumed, mammals convert vaccenic acid into rumenic
acid, which is a conjugated linoleic acid that exhibits
anticarcinogenic properties. Additionally, a diet enriched with
vaccenic acid may help lower total cholesterol, LDL cholesterol and
triglyceride levels.
[0156] In some embodiments the enriched lipid fraction and/or milk
fat globules may contain OBCFAs. In certain embodiments, the OBCFAs
may be present in an amount from about 0.3 g/100 kcal to about 6.1
g/100 kcal. In other embodiments OBCFAs may be present in an amount
from about 2.2 g/100 kcal to about 4.3 g/100 kcal. In yet another
embodiment OBCFAs may be present in an amount from about 3.5 g/100
kcal to about 5.7 g/100 kcal. In still other embodiments, the milk
fat globules comprise at least one OBCFA.
[0157] Typically, an infant may absorb OBCFAs while in utero and
from the breast milk of a nursing mother. Therefore, OBCFAs that
are identified in human milk are preferred for inclusion in the
milk fat globules of the nutritional composition. Addition of
OBCFAs to infant or children's formulas allows such formulas to
mirror the composition and functionality of human milk and to
promote general health and well-being.
[0158] In some embodiments, the enriched lipid fraction and/or milk
fat globules may comprise BCFAs. In some embodiments the BCFAs are
present at a concentration from about 0.2 g/100 kcal and about 5.82
g/100 kcal. In another embodiment, the BCFAs are present in an
amount of from about 2.3 g/100 kcal to about 4.2 g/100 kcal. In yet
another embodiment the BCFAs are present from about 4.2 g/100 kcal
to about 5.82 g/100 kcal. In still other embodiments, the milk fat
globules comprise at least one BCFA.
[0159] BCFAs that are identified in human milk are preferred for
inclusion in the nutritional composition. Addition of BCFAs to
infant or children's formulas allows such formulas to mirror the
composition and functionality of human milk and to promote general
health and well-being.
[0160] In certain embodiments the enriched lipid fraction and/or
milk fat globules may comprise CLA. In some embodiments CLA may be
present in a concentration from about 0.4 g/100 kcal to about 2.5
g/100 kcal. In other embodiments CLA may be present from about 0.8
g/100 kcal to about 1.2 g/100 kcal. In yet other embodiments CLA
may be present from about 1.2 g/100 kcal to about 2.3 g/100 kcal.
In still other embodiments, the milk fat globules comprise at least
one CLA.
[0161] CLAs that are identified in human milk are preferred for
inclusion in the nutritional composition. Typically, CLAs are
absorbed by the infant from the human milk of a nursing mother.
Addition of CLAs to infant or children's formulas allows such
formulas to mirror the composition and functionality of human milk
and to promote general health and wellbeing.
[0162] Examples of CLAs found in the milk fat globules for the
nutritional composition include, but are not limited to, cis-9,
trans-11 CLA, trans-10, cis-12 CLA, cis-9, trans-12 octadecadienoic
acid, and mixtures thereof.
[0163] The enriched lipid fraction and/or milk fat globules of the
present disclosure comprise monounsaturated fatty acids in some
embodiments. The enriched lipid fraction and/or milk fat globules
may be formulated to include monounsaturated fatty acids from about
0.8 g/100 kcal to about 2.5 g/100 kcal. In other embodiments the
milk fat globules may include monounsaturated fatty acids from
about 1.2 g/100 kcal to about 1.8 g/100 kcal.
[0164] Examples of monounsaturated fatty acids suitable include,
but are not limited to, palmitoleic acid, cis-vaccenic acid, oleic
acid, and mixtures thereof.
[0165] In certain embodiments, the enriched lipid fraction and/or
milk fat globules of the present disclosure comprise
polyunsaturated fatty acids from about 2.3 g/100 kcal to about 4.4
g/100 kcal. In other embodiments, the polyunsaturated fatty acids
are present from about 2.7 g/100 kcal to about 3.5 g/100 kcal. In
yet another embodiment, the polyunsaturated fatty acids are present
from about 2.4 g/100 kcal to about 3.3 g/100 kcal.
[0166] In some embodiments, the enriched lipid fraction and/or milk
fat globules of the present disclosure comprise polyunsaturated
fatty acids, such as, for example linoleic acid, linolenic acid,
octadecatrienoic acid, arachidonic acid (ARA), eicosatetraenoic
acid, eicopsapentaenoic acid (EPA), docosapentaenoic acid (DPA),
and docosahexaenoic acid (DHA). Polyunsaturated fatty acids are the
precursors for prostaglandins and eicosanoids, which are known to
provide numerous health benefits, including, anti-inflammatory
response, cholesterol absorption, and increased bronchial
function.
[0167] The enriched lipid fraction and/or milk fat globules of the
present disclosure can also comprise cholesterol in some
embodiments from about 100 mg/100 kcal to about 400 mg/100 kal. In
another embodiment, cholesterol is present from about 200 mg/100
kcal to about 300 mg/100 kcal. As is similar to human milk and
bovine milk, the cholesterol included in the milk fat globules may
be present in the outer bilayer membrane of the milk fat globule to
provide stability to the globular membrane.
[0168] In some embodiments, the enriched lipid fraction and/or milk
fat globules of the present disclosure comprise phospholipids from
about 50 mg/100 kcal to about 200 mg/100 kcal. In other
embodiments, the phospholipids are present from about 75 mg/100
kcal to about 150 mg/100 kcal. In yet other embodiments, the
phospholipids are present at a concentration of from about 100
mg/100 kcal to about 250 mg/100 kcal.
[0169] In certain embodiments, phospholipids may be incorporated
into the milk fat globules to stabilize the milk fat globule by
providing a phospholipid membrane or bilayer phospholipid membrane.
Therefore, in some embodiments the milk fat globules may be
formulated with higher amounts of phospholipids than those found in
human milk.
[0170] The phospholipid composition of human milk lipids, as the
weight percent of total phospholipids, is phosphatidylcholine
("PC") 24.9%, phosphatidylethanolamine ("PE") 27.7%,
phosphatidylserine ("PS") 9.3%, phosphatidylinositol ("PI") 5.4%,
and sphingomyelin ("SPM") 32.4%, (Harzer, G. et al., Am. J. Clin.
Nutr., Vol. 37, pp. 612-621 (1983)). Thus in one embodiment, the
milk fat globules comprise one or more of PC, PE, PS, PI, SPM, and
mixtures thereof. Further, the phospholipid composition included in
the milk fat globules may be formulated to provide certain health
benefits by incorporating desired phospholipids.
[0171] In certain embodiments, the enriched lipid fraction and/or
milk fat globules of the present disclosure comprise milk fat
globule membrane protein. In some embodiments, the milk fat globule
membrane protein is present from about 50 mg/100 kcal to about 500
mg/100 kcal.
[0172] Galactolipids may be included, in some embodiments, in the
enriched lipid fraction and/or milk fat globules of the present
disclosure. For purposes of this disclosure "galactolipids" refer
to any glycolipid whose sugar group is galactose. More
specifically, galactolipids differ from glycosphingolipids in that
they do not have nitrogen in their composition. Galactolipids play
an important role in supporting brain development and overall
neuronal health. Additionally, the galactolipids,
galactocerebroside and sulfatides constitute about 23% and 4% of
total myelin lipid content respectively, and thus may be
incorporated into the milk fat globules in some embodiments.
[0173] Additionally, the nutritional compositions of the present
disclosure comprise at least one source of pectin. The source of
pectin may comprise any variety or grade of pectin known in the
art. In some embodiments, the pectin has a degree of esterification
of less than 50% and is classified as low methylated ("LM") pectin.
In some embodiments, the pectin has a degree of esterification of
greater than or equal to 50% and is classified as high-ester or
high methylated ("HM") pectin. In still other embodiments, the
pectin is very low ("VL") pectin, which has a degree of
esterification that is less than approximately 15%. Further, the
nutritional composition of the present disclosure may comprise LM
pectin, HM pectin, VL pectin, or any mixture thereof. The
nutritional composition may include pectin that is soluble in
water. And, as known in the art, the solubility and viscosity of a
pectin solution are related to the molecular weight, degree of
esterification, concentration of the pectin preparation and the pH
and presence of counterions.
[0174] Moreover, pectin has a unique ability to form gels.
Generally, under similar conditions, a pectin's degree of gelation,
the gelling temperature, and the gel strength are proportional to
one another, and each is generally proportional to the molecular
weight of the pectin and inversely proportional to the degree of
esterification. For example, as the pH of a pectin solution is
lowered, ionization of the carboxylate groups is repressed, and, as
a result of losing their charge, saccharide molecules do not repel
each other over their entire length. Accordingly, the
polysaccharide molecules can associate over a portion of their
length to form a gel. Yet pectins with increasing degrees of
methylation will gel at somewhat higher pH because they have fewer
carboxylate anions at any given pH. (J. N. Bemiller, An
Introduction to Pectins: Structure and Properties, Chemistry and
Function of Pectins; Chapter 1; 1986.)
[0175] The nutritional composition may comprise a gelatinized
and/or pregelatinized starch together with pectin and/or
gelatinized pectin. While not wishing to be bound by this or any
other theory, it is believed that the use of pectin, such as LM
pectin, which is a hydrocolloid of large molecular weight, together
with starch granules, provides a synergistic effect that increases
the molecular internal friction within a fluid matrix. The
carboxylic groups of the pectin may also interact with calcium ions
present in the nutritional composition, thus leading to an increase
in viscosity, as the carboxylic groups of the pectin form a weak
gel structure with the calcium ion(s), and also with peptides
present in the nutritional composition. In some embodiments, the
nutritional composition comprises a ratio of starch to pectin that
is between about 12:1 and 20:1, respectively. In other embodiments,
the ratio of starch to pectin is about 17:1. In some embodiments,
the nutritional composition may comprise between about 0.05 and
about 2.0% w/w pectin. In a particular embodiment, the nutritional
composition may comprise about 0.5% w/w pectin.
[0176] Pectins for use herein typically have a peak molecular
weight of 8,00 Daltons or greater. The pectins of the present
disclosure have a preferred peak molecular weight of between 8,000
and about 500,00, more preferred is between about 10,00 and about
200,00 and most preferred is between about 15,00 and about 100,00
Daltons. In some embodiments, the pectin of the present disclosure
may be hydrolyzed pectin. In certain embodiments, the nutritional
composition comprises hydrolyzed pectin having a molecular weight
less than that of intact or unmodified pectin. The hydrolyzed
pectin of the present disclosure can be prepared by any means known
in the art to reduce molecular weight. Examples of said means are
chemical hydrolysis, enzymatic hydrolysis and mechanical shear. A
preferred means of reducing the molecular weight is by alkaline or
neutral hydrolysis at elevated temperature. In some embodiments,
the nutritional composition comprises partially hydrolyzed pectin.
In certain embodiments, the partially hydrolyzed pectin has a
molecular weight that is less than that of intact or unmodified
pectin but more than 3,300 Daltons.
[0177] The nutritional composition may contain at least one acidic
polysaccharide. An acidic polysaccharide, such as negatively
charged pectin, may induce an anti-adhesive effect on pathogens in
a subject's gastrointestinal tract. Indeed, nonhuman milk acidic
oligosaccharides derived from pectin are able to interact with the
epithelial surface and are known to inhibit the adhesion of
pathogens on the epithelial surface.
[0178] In some embodiments, the nutritional composition comprises
at least one pectin-derived acidic oligosaccharide. Pectin-derived
acidic oligosaccharide(s) (pAOS) result from enzymatic
pectinolysis, and the size of a pAOS depends on the enzyme use and
on the duration of the reaction. In such embodiments, the pAOS may
beneficially affect a subject's stool viscosity, stool frequency,
stool pH and/or feeding tolerance. The nutritional composition of
the present disclosure may comprise between about 2 g pAOS per
liter of formula and about 6 g pAOS per liter of formula. In an
embodiment, the nutritional composition comprises about 0.2 g
pAOS/dL, corresponding to the concentration of acidic
oligosaccharides in human milk. (Fanaro et al., "Acidic
Oligosaccharides from Pectin Hydrolysate as New Component for
Infant Formulae: Effect on Intestinal Flora, Stool Characteristics,
and pH", Journal of Pediatric Gastroenterology and Nutrition, 41:
186-190, August 2005)
[0179] In some embodiments, the nutritional composition comprises
up to about 20% w/w of a mixture of starch and pectin. In some
embodiments, the nutritional composition comprises up to about 19%
starch and up to about 1% pectin. In other embodiments, the
nutritional composition comprises about up to about 15% starch and
up to about 5% pectin. In still other embodiments, the nutritional
composition comprises up to about 18% starch and up to about 2%
pectin. In some embodiments the nutritional composition comprises
between about 0.05% w/w and about 20% w/w of a mixture of starch
and pectin. Other embodiments include between about 0.05% and about
19% w/w starch and between about 0.05% and about 1% w/w pectin.
Further, the nutritional composition may comprise between about
0.05% and about 15% w/w starch and between about 0.05% and about 5%
w/w pectin.
[0180] In some embodiments the nutritional composition comprises
sialic acid. Sialic acids are a family of over 50 members of
9-carbon sugars, all of which are derivatives of neuroaminic acid.
The predominant sialic acid family found in humans is from the
N-acetylneuraminic acid sub-family. Sialic acids are found in milk,
such as bovine and caprine. In mammals, neuronal cell membranes
have the highest concentration of sialic acid compared to other
body cell membranes. Sialic acid residues are also components of
gangliosides.
[0181] If included in the nutritional composition, sialic acid may
be present in an amount from about 0.5 mg/100 kcals to about 45
mg/100 kcal. In some embodiments sialic acid may be present in an
amount from about 5 mg/100 kcals to about 30 mg/100 kcals. In still
other embodiments, sialic acid may be present in an amount from
about 10 mg/100 kcals to about 25 mg/100 kcals.
[0182] In one embodiment, the nutritional composition may contain
one or more probiotics. 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 (LGG) (ATCC number 53103),
Bifidobacterium species, Bifidobacterium longum BB.sub.536 (BL999,
ATCC: BAA-999), Bifidobacterium longum AH1206 (NCIMB : 41382),
Bifidobacterium breve AH1205 (NCIMB: 41387), Bifidobacterium
infantis 35624 (NCIMB: 4100 3), and Bifidobacterium animalis subsp.
lactis BB-12 (DSM No. 10140) or any combination thereof.
[0183] If included in the composition, the amount of the probiotic
may vary from about 1.times.10.sup.4to about 1.5.times.10.sup.12cfu
of probiotic(s) per 100 kcal. In some embodiments the amount of
probiotic may be from about 1.times.10.sup.6to about
1.times.10.sup.9 cfu of probiotic(s) per 100 kcal. In certain other
embodiments the amount of probitic may vary from about
1.times.10.sup.7cfu/100 kcal to about 1.times.10.sup.8cfu of
probiotic(s) per 100 kcal.
[0184] 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 source is now known or
later developed.
[0185] In some embodiments, the nutritional composition may include
a source comprising probiotic cell equivalents, which refers to the
level of non-viable, non-replicating probiotics equivalent to an
equal number of viable cells. The term "non-replicating" is to be
understood as the amount of non-replicating microorganisms obtained
from the same amount of replicating bacteria (cfu/g), including
inactivated probiotics, fragments of DNA, cell wall or cytoplasmic
compounds. In other words, the quantity of non-living,
non-replicating organisms is expressed in terms of cfu as if all
the microorganisms were alive, regardless whether they are dead,
non-replicating, inactivated, fragmented etc. In non-viable
probiotics are included in the nutritional composition, the amount
of the probiotic cell equivalents may vary from about
1.times.10.sup.4 to about 1.5.times.10.sup.10 cell equivalents of
probiotic(s) per 100 kcal. In some embodiments the amount of
probiotic cell equivalents may be from about 1.times.10.sup.6to
about 1.times.10.sup.9cell equivalents of probiotic(s) per 100 kcal
nutritional composition. In certain other embodiments the amount of
probiotic cell equivalents may vary from about 1.times.10.sup.7to
about 1.times.10.sup.8 cell equivalents of probiotic(s) per 100
kcal of nutritional composition.
[0186] In some embodiments, the probiotic source incorporated into
the nutritional composition may comprise both viable colony-forming
units, and non-viable cell-equivalents.
[0187] In some embodiments, the nutritional composition includes a
culture supernatant from a late-exponential growth phase of a
probiotic batch-cultivation process. Without wishing to be bound by
theory, it is believed that the activity of the culture supernatant
can be attributed to the mixture of components (including
proteinaceous materials, and possibly including (exo)polysaccharide
materials) as found released into the culture medium at a late
stage of the exponential (or "log") phase of batch cultivation of
the probiotic. The term "culture supernatant" as used herein,
includes the mixture of components found in the culture medium. The
stages recognized in batch cultivation of bacteria are known to the
skilled person. These are the "lag," the "log" ("logarithmic" or
"exponential"), the "stationary" and the "death" (or "logarithmic
decline") phases. In all phases during which live bacteria are
present, the bacteria metabolize nutrients from the media, and
secrete (exert, release) materials into the culture medium. The
composition of the secreted material at a given point in time of
the growth stages is not generally predictable.
[0188] In an embodiment, a culture supernatant is obtainable by a
process comprising the steps of (a) subjecting a probiotic such as
LGG to cultivation in a suitable culture medium using a batch
process; (b) harvesting the culture supernatant at a late
exponential growth phase of the cultivation step, which phase is
defined with reference to the second half of the time between the
lag phase and the stationary phase of the batch-cultivation
process; (c) optionally removing low molecular weight constituents
from the supernatant so as to retain molecular weight constituents
above 5-6 kiloDaltons (kDa); (d) removing liquid contents from the
culture supernatant so as to obtain the composition.
[0189] The culture supernatant may comprise secreted materials that
are harvested from a late exponential phase. The late exponential
phase occurs in time after the mid exponential phase (which is
halftime of the duration of the exponential phase, hence the
reference to the late exponential phase as being the second half of
the time between the lag phase and the stationary phase). In
particular, the term "late exponential phase" is used herein with
reference to the latter quarter portion of the time between the lag
phase and the stationary phase of the LGG batch-cultivation
process. In some embodiments, the culture supernatant is harvested
at a point in time of 75% to 85% of the duration of the exponential
phase, and may be harvested at about of the time elapsed in the
exponential phase.
[0190] As noted, the disclosed nutritional composition may comprise
a source of .beta.-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 (.beta.-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.
[0191] .beta.-1,3-glucans are carbohydrate polymers purified from,
for example, yeast, mushroom, bacteria, algae, or cereals. (Stone B
A, Clarke A E. Chemistry and Biology of (1-3)-Beta-Glucans.
London:Portland Press Ltd; 1993.) The chemical structure of
.beta.-1,3-glucan depends on the source of the .beta.-1,3-glucan.
Moreover, various physiochemical parameters, such as solubility,
primary structure, molecular weight, and branching, play a role in
biological activities of .beta.-1,3-glucans. (Yadomae T., Structure
and biological activities of fungal beta-1,3-glucans. Yakugaku
Zasshi. 2000; 120:413-431.)
[0192] .beta.-1,3-glucans are naturally occurring polysaccharides,
with or without .beta.-1,6-glucose side chains that are found in
the cell walls of a variety of plants, yeasts, fungi and bacteria.
.beta.l -1,3;1,6-glucans are those containing glucose units with
(1,3) links having side chains attached at the (1,6) position(s).
.beta.-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 .beta.-1,3 bond with
.beta.-1,6-linked glucose branches extending from this backbone.
While this is the basic structure for the presently described class
of .beta.-glucans, some variations may exist. For example, certain
yeast .beta.-glucans have additional regions of .beta.(1,3)
branching extending from the .beta.(1,6) branches, which add
further complexity to their respective structures.
[0193] .beta.-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 .beta.-glucan is an insoluble,
fiber-like, complex sugar having the general structure of a linear
chain of glucose units with a .beta.-1,3 backbone interspersed with
.beta.-1,6 side chains that are generally 6-8 glucose units in
length. More specifically, .beta.-glucan derived from baker's yeast
is
poly-(1,6)-.beta.-D-glucopyranosyl-(1,3)-.beta.-D-glucopyranose.
[0194] Furthermore, .beta.-glucans are well tolerated and do not
produce or cause excess gas, abdominal distension, bloating or
diarrhea in pediatric subjects. Addition of .beta.-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.
[0195] The nutritional composition of the present disclosure
comprises .beta.-glucan. In some embodiments, the .beta.-glucan is
.beta.-1,3;1,6-glucan. In some embodiments, the
.beta.-1,3;1,6-glucan is derived from baker's yeast. The
nutritional composition may comprise whole glucan particle
.beta.-glucan, particulate .beta.-glucan, PGG-glucan
(poly-1,6-.beta.-D-glucopyranosyl-1,3-.beta.-D-glucopyranose) or
any mixture thereof.
[0196] In some embodiments, the amount of .beta.-glucan present in
the composition is at between about 0.010 and about 0.080 g per 100
g of composition. In other embodiments, the nutritional composition
comprises between about 10 and about 30 mg .beta.-glucan per
serving. In another embodiment, the nutritional composition
comprises between about 5 and about 30 mg .beta.-glucan per 8 fl.
oz. (236.6 mL) serving. In other embodiments, the nutritional
composition comprises an amount of .beta.-glucan sufficient to
provide between about 15 mg and about 90mg 3-glucan per day. The
nutritional composition may be delivered in multiple doses to reach
a target amount of .beta.-glucan delivered to the subject
throughout the day.
[0197] In some embodiments, the amount of .beta.-glucan in the
nutritional composition is between about 3 mg and about 17 mg per
100 kcal. In another embodiment the amount of .beta.-glucan is
between about 6 mg and about 17 mg per 100 kcal.
[0198] The nutritional composition of this disclosure may also
include phosphatidylethanolamine ("PE"), recognized as having
neurogenesis-promoting effects, particularly in infants, as taught
by Ser. No. 13/739,787, filed Jan. 11, 2013. It is believed that PE
may synergistically work with inositol to enhance the effects noted
herein. Examples of PE suitable for inclusion in the neurologic
component include, but are not limited to,
1,2-Dierucoyl-sn-glycero-3-phosphoethanolamine,
1,2-Dilauroyl-sn-glycero-3-phosphoethanolamine,
1,2-Dimyristoyl-sn-glycero-3-phosphoethanolamine,
1,2-Dioleoyl-sn-glycero-3-phosphoethanolamine,
1,2-Dipalmitoyl-sn-glycero-3 -phosphoethanolamine,
1,2-Distearoyl-sn-glycero-3 -phosphoethanolamine,
1-Palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine,
1-arachidonoyl-2-stearoyl-sn-glycerol 3 -phosphoethanolamine,
N,1-Diarachi donoyl-2-stearoyl-sn-glycerol 3-phosphoethanolamine,
and phosphoethanolanime containing any fatty acid at the 1 and/or 2
positions.
[0199] PE may be present, in some embodiments, in an amount from
about 3.7 mg/100 kcal to about 37 mg/100 kcal. In other
embodiments, PE may be present from about 10 mg/100 kcal to about
30 mg/100 kcal. In still other embodiments, PE may be present from
about 15 mg/100 kcal to about 25 mg/100 kcal.
[0200] Sphingomyelin has also been recognized as having
neurogenesis-promoting effects, particularly in infants, as taught
by Ser. No. 13/739,787, filed Jan. 11, 2013, and can be
incorporated into the nutritional composition of the present
disclosure in certain embodiments, to synergistically combine with
inositol to further improve the disclosed neurological benefits.
Sphingomyelin refers to a class of sphingolipids found in animal
cell membranes, particularly in the myelin sheath that surrounds
nervous cell axons. In humans, sphingomyelin typically makes up 10%
to 20% of plasma membrane lipids. It is believed that sphingomyelin
serves to electrically insulate nerve cell axons as it makes up 25%
the total lipids in the myelin sheath that surround and insulate
cells of the central nervous system. Membrane sphingomyelin is the
precursor for sphingosine which is the precursor for
sphingosine-1-phosphate, which may have a role in neurogenesis and
is neuroprotective. Sphingosine-1-phosphate may also facilitate
neural stem/progenitor cell ("NSPC") migration, which is essential
to the development of the nervous system as well as the ongoing
neurogenesis that occurs in the mature central nervous system.
[0201] Examples of sphingomyelin suitable for inclusion in the
neurologic component of the nutritional composition include but are
not limited to ceramide phosphorylcholine and ceramide
phosphorylethanolamine, N-oleoyl sphingomyelin, N-stearoyl
sphingomyelin, and/or D-erythro N-palmitoyl sphingomyelin, and
mixtures thereof. For example, in one embodiment the sphingomyelin
included in the neurologic component may be synthetic sphingomyelin
prepared according to the procedures of U.S. Pat. No. 7,687,652 to
Rochlin et al., however, the present disclosure can also include
other processes for production of synthetic sphingomyelin.
[0202] When present, sphingomyelin can be incorporated at a level
of about 0.15 mg/100 kcal to about 73 mg/100 kcal.
[0203] Alpha-lipoic acid (ALA) can also be incorporated into the
nutritional composition of the present disclosure in some
embodiments. ALA has been recognized as having
neurogenesis-promoting effects, particularly in infants, as taught
by Ser. No. 13/942,794, filed Jul. 16, 2013. ALA may, under certain
circumstances, synergistically combine with inositol to further
improve the neurological benefits of inositol. Examples of ALA
suitable for use herein include, but are not limited to,
enantiomers and racemic mixtures of ALA, including, R-lipoic acid
"RLA", S-lipoic acid "SLA", and R/S-LA. Also suitable is R-lipoic
acid stabilized with either sodium ("Na-RALA") or potassium as
Potassium-R-Lipoate.
[0204] When incorporated into the disclosed nutritional
composition, ALA may be present, in some embodiments, in an amount
from about 0.1 mg/100 kcal to about 35 mg/100 kcal. In some
embodiments, ALA may be present in an amount from about 20 mg/100
kcal to about 25 mg/100 kcal. In still other embodiments, ALA may
be present in an amount from about 5.0 mg/100 kcal to about 15
mg/100 kcal.
[0205] In certain embodiments, the nutritional composition of the
present disclosure further comprises epigallocatchin-gallate
(EGCG), which has been recognized as having neurogenesis-promoting
effects, particularly in infants, as taught by Ser. No. 14/044,913,
filed Oct. 3, 2013. It is believed that EGCG may synergistically
combine with inositol to further improve the neurological benefits
of inositol, especially when EGCG is present in the disclosed
nutritional composition at a level of about 5 mg/100 kcal to about
120 mg/100 kcal.
[0206] Sulforaphane, which includes L-sulforaphane, may be
incorporated into the nutritional composition in an amount from
about 1.5 mg/100 kcal to about 7.5 mg/100 kcal. Still in some
embodiments, sulforaphane may be present in an amount from about 2
mg/100 kcal to about 6 mg/100 kcal. In some embodiments,
sulforaphane may be present in an amount from about 3 mg/100 kcal
to about 5 mg/100 kcal. Sulforaphane has been recognized as having
neurogenesis-promoting effects, particularly in infants, as taught
by Ser. No. 13/942,794, filed Jul. 16, 2013, and may also exhibit
synergy with inositol herein.
[0207] 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.
[0208] The nutritional composition may optionally include, but is
not limited to, one or more of the following vitamins or
derivations thereof: vitamin Bi (thiamin, thiamin pyrophosphate,
TPP, thiamin triphosphate, TTP, thiamin hydrochloride, thiamin
mononitrate), vitamin B.sub.2 (riboflavin, flavin mononucleotide,
FMN, flavin adenine dinucleotide, FAD, lactoflavin, ovoflavin),
vitamin B.sub.3 (niacin, nicotinic acid, nicotinamide, niacinamide,
nicotinamide adenine dinucleotide, NAD, nicotinic acid
mononucleotide, NicMN, pyridine-3-carboxylic acid), vitamin
B.sub.3-precursor tryptophan, vitamin B.sub.6 (pyridoxine,
pyridoxal, pyridoxamine, pyridoxine hydrochloride), pantothenic
acid (pantothenate, panthenol), folate (folic acid, folacin,
pteroylglutamic acid), vitamin B.sub.12 (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 D.sub.3, 1,25,-dihydroxyvitamin D), vitamin E
(.alpha.-tocopherol, .alpha.-tocopherol acetate, .alpha.-tocopherol
succinate, .alpha.-tocopherol nicotinate, .alpha.-tocopherol),
vitamin K (vitamin Ki, phylloquinone, naphthoquinone, vitamin
K.sub.2, menaquinone-7, vitamin K.sub.3, menaquinone-4, menadione,
menaquinone-8, menaquinone-8H, menaquinone-9, menaquinone-9H,
menaquinone-10, menaquinone-11, menaquinone-12, menaquinone-13),
choline, inositol, .beta.-carotene and any combinations
thereof.
[0209] Further, the nutritional 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.
[0210] The minerals can be added to 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.
[0211] In an embodiment, the 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, 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.
[0212] 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 used. The type and
amount of flavoring agent can be selected as is known in the
art.
[0213] 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.
[0214] 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.
[0215] 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.
[0216] The disclosed nutritional composition(s) may be provided in
any form known in the art, such as a powder, a gel, a suspension, a
paste, a solid, a liquid, a liquid concentrate, a reconstitutable
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 .mu.m to 1500 .mu.m,
more preferably in the range of 10 .mu.m to 300 .mu.m.
[0217] If the nutritional composition is in the form of a
ready-to-use product, the osmolality of the nutritional composition
may be between about 100 and about 1100 mOsm/kg water, more
typically about 200 to about 700 mOsm/kg water.
[0218] 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 7 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.
[0219] The nutritional composition of the present disclosure may
further include at least one additional phytonutrient, that is,
another phytonutrient component in addition to the pectin and/or
starch components described hereinabove. Phytonutrients, or their
derivatives, conjugated forms or precursors, that are identified in
human milk are preferred for inclusion in the nutritional
composition. Typically, dietary sources of carotenoids and
polyphenols are absorbed by a nursing mother and retained in milk,
making them available to nursing infants. Addition of these
phytonutrients to infant or children's formulas allows such
formulas to mirror the composition and functionality of human milk
and to promote general health and well being.
[0220] For example, in some embodiments, the nutritional
composition of the present disclosure may comprise, in an 8 fl. oz.
(236.6 mL) serving, between about 80 and about 300 mg anthocyanins,
between about 100 and about 600 mg proanthocyanidins, between about
50 and about 500 mg flavan-3-ols, or any combination or mixture
thereof. In other embodiments, the nutritional composition
comprises apple extract, grape seed extract, or a combination or
mixture thereof. Further, the at least one phytonutrient of the
nutritional composition may be derived from any single or blend of
fruit, grape seed and/or apple or tea extract(s).
[0221] For the purposes of this disclosure, additional
phytonutrients may be added to a nutritional composition in native,
purified, encapsulated and/or chemically or enzymatically-modified
form so as to deliver the desired sensory and stability properties.
In the case of encapsulation, it is desirable that the encapsulated
phytonutrients resist dissolution with water but are released upon
reaching the small intestine. This could be achieved by the
application of enteric coatings, such as cross-linked alginate and
others.
[0222] Examples of additional phytonutrients suitable for the
nutritional composition include, but are not limited to,
anthocyanins, proanthocyanidins, flavan-3-ols (i.e. catechins,
epicatechins, etc.), flavanones, flavonoids, isoflavonoids,
stilbenoids (i.e. resveratrol, etc.), proanthocyanidins,
anthocyanins, resveratrol, quercetin, curcumin, and/or any mixture
thereof, as well as any possible combination of phytonutrients in a
purified or natural form. Certain components, especially
plant-based components of the nutritional compositions may provide
a source of phytonutrients.
[0223] Some amounts of phytonutrients may be inherently present in
known ingredients, such as natural oils, that are commonly used to
make nutritional compositions for pediatric subjects. These
inherent phytonutrient(s) ma