U.S. patent application number 16/915513 was filed with the patent office on 2020-10-15 for oral rehydration composition with oligosaccharides.
This patent application is currently assigned to ABBOTT LABORATORIES. The applicant listed for this patent is ABBOTT LABORATORIES. Invention is credited to JOMAY CHOW, NED MCCOY, PEDRO PRIETO.
Application Number | 20200323890 16/915513 |
Document ID | / |
Family ID | 1000004929047 |
Filed Date | 2020-10-15 |
United States Patent
Application |
20200323890 |
Kind Code |
A1 |
CHOW; JOMAY ; et
al. |
October 15, 2020 |
ORAL REHYDRATION COMPOSITION WITH OLIGOSACCHARIDES
Abstract
The general inventive concepts are directed to compositions and
methods for the prevention and treatment of dehydration. Provided
herein are nutritional compositions including oral rehydration
compositions. Certain embodiments of the nutritional compositions
have an acidic pH, and comprise a digestible carbohydrate, sodium,
citrate, and an oligosaccharide selected from a fucosylated
oligosaccharide and an N-acetylated oligosaccharide.
Inventors: |
CHOW; JOMAY; (Westerville,
OH) ; PRIETO; PEDRO; (Columbus, OH) ; MCCOY;
NED; (Dublin, OH) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
ABBOTT LABORATORIES |
ABBOTT PARK |
IL |
US |
|
|
Assignee: |
ABBOTT LABORATORIES
ABBOTT PARK
IL
|
Family ID: |
1000004929047 |
Appl. No.: |
16/915513 |
Filed: |
June 29, 2020 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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15106568 |
Jun 20, 2016 |
10695358 |
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PCT/US14/71578 |
Dec 19, 2014 |
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16915513 |
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61919004 |
Dec 20, 2013 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61K 2035/115 20130101;
A61K 31/717 20130101; A61K 33/00 20130101; A23L 29/30 20160801;
A23L 2/52 20130101; A23L 33/10 20160801; A61K 9/0095 20130101; A61K
33/14 20130101; A61K 31/194 20130101; A23L 33/16 20160801; A23V
2002/00 20130101; A23L 2/39 20130101; A61K 31/7004 20130101; A23L
33/21 20160801; A61K 33/30 20130101; A61K 35/741 20130101; A61K
31/702 20130101; A23L 33/125 20160801 |
International
Class: |
A61K 31/702 20060101
A61K031/702; A61K 9/00 20060101 A61K009/00; A23L 33/16 20060101
A23L033/16; A23L 33/21 20060101 A23L033/21; A23L 2/52 20060101
A23L002/52; A23L 2/39 20060101 A23L002/39; A23L 29/30 20060101
A23L029/30; A23L 33/10 20060101 A23L033/10; A23L 33/125 20060101
A23L033/125; A61K 31/194 20060101 A61K031/194; A61K 31/7004
20060101 A61K031/7004; A61K 31/717 20060101 A61K031/717; A61K 33/00
20060101 A61K033/00; A61K 33/14 20060101 A61K033/14; A61K 33/30
20060101 A61K033/30; A61K 35/741 20060101 A61K035/741 |
Claims
1-42. (canceled)
43. A nutritional composition comprising: a human milk
oligosaccharide selected from the group consisting of a fucosylated
oligosaccharide, an N-acetylated oligosaccharide, and combinations
thereof in an amount of 10 mg to 5000 mg per liter of the
nutritional composition; a digestible carbohydrate in addition to
the human milk oligosaccharide in an amount of from 10 mM to 150 mM
of carbohydrate of the nutritional composition; and sodium in an
amount of 10 mEq to 100 mEq of sodium per liter of the nutritional
composition; and wherein the nutritional composition is shelf
stable for at least three months.
44. The nutritional composition of claim 43, wherein the human milk
oligosaccharide is selected from 2'-fucosyllactose and
lacto-N-neotetraose.
45. The nutritional composition of claim 44, wherein the human milk
oligosaccharide is 2'-fucosyllactose.
46. The nutritional composition of claim 45, wherein the
2'-fucosyllactose is present in an amount of 20 mg to 4000 mg per
liter of the nutritional composition.
47. The nutritional composition of claim 45 further comprising at
least one neutral human milk oligosaccharide.
48. The nutritional composition of claim 43 wherein the nutritional
composition does not comprise a sialylated oligosaccharide.
49. The nutritional composition of claim 43, wherein the
nutritional composition is shelf stable for at least six
months.
50. The nutritional composition of claim 45 further comprising
galactooligosaccharides.
51. The nutritional composition of claim 45 further comprising at
least one of protein and fat.
52. The nutritional composition of claim 45, wherein the digestible
carbohydrate is selected from the group consisting of dextrose,
maltodextrin, starch, isomaltulose, sucromalt, rice syrup, and rice
syrup solids.
53. The nutritional composition of claim 45, wherein the digestible
carbohydrate is dextrose.
54. The nutritional composition of claim 45, wherein the sodium is
selected from the group consisting of sodium chloride, sodium
phosphate, sodium citrate, sodium carbonate, sodium bicarbonate,
sodium hydroxide, sodium ascorbate and combinations thereof.
55. The nutritional composition of claim 45 further comprising a
probiotic.
56. The nutritional composition of claim 45 further comprising
chloride.
57. The nutritional composition of claim 56, wherein the chloride
is selected from the group consisting of sodium chloride, potassium
chloride, calcium chloride, magnesium chloride, and combinations
thereof.
58. The nutritional composition of claim 45 further comprising
zinc.
59. The nutritional composition of claim 58, wherein the zinc is
selected from the group consisting of zinc gluconate, zinc sulfate,
zinc chloride, zinc citrate, zinc bicarbonate, zinc carbonate, zinc
hydroxide, zinc lactate, zinc acetate, zinc fluoride, zinc bromide,
zinc sulfonate, and combinations thereof.
60. The nutritional composition of claim 45 further comprising
citrate.
61. The nutritional composition of claim 60, wherein the citrate is
selected from the group consisting of potassium citrate, sodium
citrate, zinc citrate, and combinations thereof.
62. An aqueous oral rehydration composition comprising: a human
milk oligosaccharide selected from the group consisting of a
fucosylated oligosaccharide, an N-acetylated oligosaccharide, and
combinations thereof in an amount of 10 mg to 5000 mg per liter of
the nutritional composition; a digestible carbohydrate in addition
to the human milk oligosaccharide in an amount of from 10 mM to 150
mM of carbohydrate of the nutritional composition; and sodium in an
amount of 10 mEq to 100 mEq of sodium per liter of the nutritional
composition; wherein the aqueous oral rehydration composition has a
pH of about 2 to about 6.5 and is shelf stable for at least three
months after heat sterilization.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application claims priority to and any benefit of U.S.
Provisional Application No. 61/919,004, filed Dec. 20, 2013, the
content of which is incorporated herein by reference in its
entirety.
TECHNICAL FIELD
[0002] The general inventive concepts are directed to compositions
and methods for the treatment of dehydration, and more particularly
to oral rehydration compositions and uses thereof.
BACKGROUND
[0003] Dehydration resulting from fever, diarrhea, vomiting, or
combinations thereof, is a leading cause of morbidity and mortality
in the developing world. While not generally considered a
substantial worry for healthy individuals in developed countries,
it remains a considerable health concern for those in poor or
compromised health. One method for treating dehydration is
administration of an Oral Rehydration Composition(s) (ORC). In
general, when consumed by an individual afflicted with dehydration,
an ORC supplies necessary calories and electrolytes that otherwise
the individual would have difficulty absorbing. This is
accomplished through a balance between the amount of carbohydrates
and the amount of electrolytes in the ORC. For example, sodium
absorption improves as the dextrose concentration of the oral fluid
is increased up to about 2.5% w/w. But higher concentrations of
dextrose increase the osmotic load in the gut, which pulls water
out of the blood stream, leading to a net reduction in sodium and
water absorption. This net loss of fluids and electrolytes further
exacerbates dehydration.
[0004] However, only certain carbohydrates have been shown to be
effective in aiding absorption of electrolytes. Generally, simple
sugars such as dextrose and fructose are effective while larger
carbohydrates do not provide the same benefit. Further, many
oligosaccharides are known to have limited stability in acidic
medium such as is common to ORC. Because of this, conventional ORC
generally do not include oligosaccharides or polysaccharides.
SUMMARY
[0005] The general inventive concepts are directed to nutritional
compositions including oral rehydration compositions, and the use
of nutritional compositions including oral rehydration compositions
to prevent or treat dehydration. In certain exemplary embodiments,
an oral rehydration composition comprising a human milk
oligosaccharide is provided.
[0006] In a first exemplary embodiment, a nutritional composition
is provided. The nutritional composition comprises a human milk
oligosaccharide selected from a fucosylated oligosaccharide, an
N-acetylated oligosaccharide, and combinations thereof in an amount
of about 10 mg to about 5000 mg per liter of the nutritional
composition; a digestible carbohydrate in addition to the human
milk oligosaccharide in an amount of from about 10 mM to about 150
mM of carbohydrate per liter of the nutritional composition; and
sodium in an amount of about 10 mEq to about 100 mEq of sodium per
liter of the nutritional composition.
[0007] In a second exemplary embodiment, an oral rehydration
composition is provided. The oral rehydration composition comprises
sodium, potassium, chloride, a digestible carbohydrate, an
indigestible carbohydrate, and a human milk oligosaccharide in an
amount of about 10 mg to about 5000 mg per liter of the oral
rehydration composition.
[0008] In a third exemplary embodiment, an acidic,
thermally-treated nutritional liquid is provided. The nutritional
liquid comprises at least one of 2'-fucosyllactose and
lacto-N-neotetraose in an amount of from about 10 mg to about 5000
mg per liter of the nutritional liquid.
[0009] In a fourth exemplary embodiment, an oral rehydration
composition is provided. The oral rehydration composition comprises
sodium, potassium, chloride, a digestible carbohydrate, and at
least one human milk oligosaccharide selected from a fucosylated
oligosaccharide and a N-acetylated oligosaccharide.
DETAILED DESCRIPTION
[0010] The general inventive concepts are directed to nutritional
compositions including ORC, and the use of nutritional compositions
to prevent or treat dehydration. In certain embodiments, the ORC
has an acidic pH, and comprises a digestible carbohydrate, sodium,
and an oligosaccharide. Compositions according to the exemplary
embodiments may be useful for at least one of: rehydration,
promoting faster recovery from diarrhea) illness, reducing
intestinal spasms due to diarrhea, reducing the duration of
diarrhea, reducing vomiting and nausea, and promoting faster
re-colonization of the gastrointestinal (GI) tract by beneficial
flora following antibiotic treatment.
[0011] The term "individual" as used herein, unless otherwise
specified, refers to a mammal. In certain exemplary embodiments,
the individual is a human, including an infant, a child and an
adult.
[0012] The term "infant" as used herein, unless otherwise
specified, refers to children not more than about one year of age,
and includes infants from 0 to about 4 months of age, infants from
about 4 to about 8 months of age, infants from about 8 to about 12
months of age, low birth weight infants at less than 2,500 grams at
birth, and preterm infants born at less than about 37 weeks
gestational age, typically from about 26 weeks to about 34 weeks
gestational age. The term "child" or "children" as used herein
refers to children not more than 12 years of age, and includes
children from about 12 months to about 12 years of age. The term
"adult" as used herein refers to adults and children about 12 years
of age and older.
[0013] One "milliequivalent" (mEq) refers to the number of ions in
solution as determined by their concentration in a given volume.
This measure is expressed as the number of milliequivalents per
liter (mEq/L). Milliequivalents may be converted to milligrams by
multiplying mEq by the atomic weight of the mineral and then
dividing that number by the valence of the mineral.
[0014] The terms "administer," "administering," "administered," or
"administration" as used herein, unless otherwise specified, should
be understood to include providing the nutritional composition to
an individual, the act of consuming the nutritional composition,
and combinations thereof. In addition, it should be understood that
the methods of administering disclosed herein may be practiced with
or without doctor supervision or other medical direction.
[0015] The terms "human milk oligosaccharide" or "HMO," unless
otherwise specified, refers generally to a number of complex
carbohydrates found in human breast milk that can be in acidic or
neutral form. Exemplary non-limiting human milk oligosaccharides
include, 2'-fucosyllactose, 3'-fucosyllactose, lacto-N-neotetraose,
and lacto-N-tetraose.
[0016] The term "shelf stable" as used herein, unless otherwise
specified, refers to a nutritional product that remains
commercially stable after being packaged and then stored at
18-24.degree. C. for at least 3 months, including from about 6
months to about 24 months, and also including from about 12 months
to about 18 months
[0017] The exemplary nutritional compositions disclosed herein, and
utilized in the exemplary methods, include those suitable for oral
administration. Oral administration, as defined herein, includes
any form of administration in which the nutritional compositions
passes through the esophagus of the individual. For example, oral
administration includes nasogastric intubation, in which a tube is
run through the nose to the stomach of the individual to administer
food or drugs.
[0018] All percentages, parts and ratios as used herein, are by
weight of the total composition, unless otherwise specified. All
such weights as they pertain to listed ingredients are based on the
active level and, therefore, do not include solvents or by-products
that may be included in commercially available materials, unless
otherwise specified.
[0019] Any reference in the specification or claims to a quantity
of an electrolyte should be construed as referring to the final
concentration of the electrolyte in the nutritional composition.
Tap water often contains residual sodium, chlorine, etc. A value of
15 mEq of sodium in this application means that the total sodium
present in the nutritional composition equals 15 mEq, taking into
account both added sodium as well as the sodium present in the
water used to manufacture the nutritional composition. This holds
true for all electrolytes.
[0020] 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.
[0021] The nutritional compositions of the present disclosure may
also be substantially free of any optional ingredient or feature
described herein, provided that the remaining formula still
contains all of the required ingredients or features as described
herein. In this context, and unless otherwise specified, the term
"substantially free" means that the selected composition contains
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 essential ingredient.
[0022] In certain exemplary embodiments, the nutritional
composition, such as an OIC, is formulated as a clear liquid (i.e.,
a solution) having an acidic pH. In certain exemplary embodiments,
the nutritional composition is an aqueous composition and has a pH
ranging from 2 to 6.5. In certain exemplary embodiments, the pH of
the nutritional composition is about 2.5 to about 4.6. In certain
exemplary embodiments, the pH of the nutritional composition is
about 2.5 to about 3.5.
[0023] Typically, the nutritional composition is desired to be
clear, or at least substantially translucent, and is substantially
free of fat. As used herein "substantially free of fat" refers to a
nutritional composition containing less than 0.5%, including less
than 0.1%, fat by weight of the total composition. "Substantially
free of fat" also may refer to a nutritional composition disclosed
herein that contains no fat, i.e., zero fat. In those embodiments
of the nutritional composition that are substantially free of fat
but have some amount of fat present, the fat may be present as a
result of being inherently present in another ingredient, or the
fat may be present as a result of being added as one or more
separate sources of fat. In certain exemplary embodiments, the term
substantially free of fat refers to a nutritional composition
wherein there is no caloric lipid component (i.e., less than a
functional amount of the ingredient, typically less than 0.5% by
weight, and also including zero percent by weight, of such
ingredient) in the nutritional composition. In certain exemplary
embodiments, a nutritional composition that includes a lipid that
is introduced as a component of one or more ingredients but does
not contribute substantially to the caloric value of the
nutritional composition is considered to be substantially free of
fat. In certain exemplary embodiments, a nutritional composition
that includes emulsifiers, phospholipids or the like, in amounts
that do not contribute substantially to the caloric value of the
nutritional composition, is considered to be substantially free of
fat.
[0024] The nutritional composition and corresponding manufacturing
methods disclosed herein can comprise, consist of, or consist
essentially of the essential elements and limitations of the
disclosure as described herein, as well as any additional or
optional ingredients, components, or limitations described herein
or otherwise useful in oral rehydration applications.
[0025] Oral Rehydration Therapy (ORT) typically involves the
administration of a nutritional composition containing, at a
minimum, a digestible carbohydrate (often dextrose) and sodium in
water. A nutritional composition such as this provides rapid,
effective hydration because sodium ion absorption in the intestines
causes water molecules associated with the sodium ion to also be
absorbed. This sodium absorption is activated by dextrose.
Specifically, dextrose that crosses the intestinal epithelium
brings sodium ions, raising the concentration of sodium ions in the
blood stream and pulling water out of the gut.
[0026] A nutritional composition can thus be used to correct the
fluid and electrolyte losses associated with acute infectious
diarrhea or vomiting, or both, to treat hyponatremia or
hypohydration due to exercise, changes in altitude, or fever, and
to maintain a healthy level of hydration. The general inventive
concepts are directed to an nutritional composition comprising
sodium, a digestible carbohydrate, and an oligosaccharide (in
particular fucosylated oligosaccharides and N-acetylated
oligosaccharides), in particular, an oligosaccharide that is stable
in an acidic environment. The general inventive concepts also
relate to the use of the nutritional compositions for the
prevention/treatment of dehydration due to fever and/or other
medical conditions not associated with diarrhea and vomiting.
[0027] Inclusion of certain oligosaccharides in ORT is complicated
by the fact that many are unstable in acidic medium (many forms of
ORT are acidic), especially when stored for extended (i.e., more
than 3 months) periods of time. When subjected to acidic medium,
the bonds between the sugars that make up the oligosaccharide are
hydrolyzed giving off the individual sugars. Nevertheless, provided
herein are nutritional compositions (including acidic nutritional
compositions such as ORC) comprising oligosaccharides, including
HMOs, which demonstrate enhanced shelf stability.
[0028] Prebiotics are generally defined as non-digestible food
ingredients that beneficially affect the host by stimulating the
growth or activity, or both, of beneficial bacteria in the colon.
These bacteria have been shown to provide benefits for digestion
and boost immune function. In this regard they may provide benefits
to those experiencing dehydration. Oligosaccharides are short to
medium chain polymers of simple carbohydrates (i.e., sugars), and
many have demonstrated prebiotic activity. Examples of
oligosaccharides include galactooligosaccharide (GOS)
2'-fucosyllactose (2'-FL) and lacto-N-neotetraose (LNnT).
[0029] Human milk is known to contain more than 100 different
oligosaccharides. Many beneficial functions have been attributed to
HMOs. Certain HMOs have been shown to be beneficial biologically.
For this reason, the supplementation nutritional compositions with
human milk oligosaccharides is desirable. The nutritional
compositions according to the general inventive concepts include at
least one HMO, and in certain embodiments, a combination of two or
more HMOs.
[0030] The HMO may be included in the nutritional compositions
alone, or in some embodiments, in combination with other components
(e.g., prebiotic oligosaccharides, probiotics, etc.) as described
herein. In many embodiments, HMOs are included in the nutritional
compositions with multiple additional components. The HMO may be
isolated or enriched from milk(s) secreted by mammals including,
but not limited to: human, bovine, ovine, porcine, or caprine
species. The 1-IMO may also be produced via microbial fermentation,
enzymatic processes, chemical synthesis, or combinations
thereof.
[0031] Suitable HMOs for use in the nutritional compositions may
generally include neutral oligosaccharides, acidic
oligosaccharides, and more particularly include fucosylated
oligosaccharides and N-acetylated oligosaccharides. Specific
non-limiting examples of HMOs that may be included individually or
in combination in the exemplary nutritional compositions include:
2'-FL; 3'-Fucosyllactose (3'-FL); Lacto-N-tetraose (LNT); and
LNnT.
[0032] Optional HMOs that may be included in certain exemplary
embodiments include sialic acid (i.e., free sialic acid,
lipid-bound sialic acid, protein-bound sialic acid); D-glucose
(Glc); D-galactose (Gal); N-acetylglucosamine (GlcNAc); L-fucose
(L-Fuc); D-fucose (D-fuc); fucosyl oligosaccharides (i.e.,
Lacto-N-fucopentaose I; Lacto-N-fucopentaose II
Lacto-N-fucopentaose III; Lacto-N-difucohexaose I; and
Lactodifucotetraose); non-fucosylated, non-sialylated
oligosaccharides (i.e); sialyl oligosaccharides (i.e.,
3'-Sialyl-3-fucosyllactose; Disialomonofucosyllacto-N-neohexaose;
Monofucosylmonosialyllacto-N-octaose (sialyl Lea);
Sialyllacto-N-fucohexaose 11; Disialyllacto-N-fucopentaose II;
Monofucosyldisialyllacto-N-tetraose); and sialyl fucosyl
oligosaccharides i.e., 2'-Sialyllactose; 2-Sialyllactosamine;
3'-Sialyllactose; 3'-Sialyllactosamine; 6'-Sialyllactose;
6'-Sialyllactosamine; Sialyllacto-N-neotetraose c;
Monosialyllacto-N-hexaose; Disialyllacto-N-hexaose I;
Monosialyllacto-N-neohexaose I; Monosialyllacto-N-neohexaose II;
Disialyllacto-N-neohexaose; Disialyllacto-N-tetraose;
Disialyllacto-N-hexaose 11; Sialyllacto-N-tetraose a;
Disialyllacto-N-hexaose I; and Sialyllacto-N-tetraose. Other
suitable examples of HMOs that may be included in the compositions
of the present disclosure include lacto-N-fucopentaose V,
lacto-N-hexaose, para-lacto-N-hexaose, lacto-N-neohexaose,
para-lacto-N-neohexaose, monofucosyllacto-N-hexaose II, isomeric
fucosylated lacto-N-hexaose (1), isomeric fucosylated
lacto-N-hexaose (3), isomeric fucosylated lacto-N-hexaose (2),
difucosyl-para-lacto-N-neohexaose, difucosyl-para-lacto-N-hexaose,
difucosyllacto-N-hexaose, lacto-N-neooctaose,
para-lacto-N-octanose, iso-lacto-N-octaose, lacto-N-octaose,
monofucosyllacto-neooctaose, monofucosyllacto-N-octaose,
difucosyllacto-N-octaose I, difucosyllacto-N-octaose II,
difucosyllacto-N-neoocataose II, difucosyllacto-N-neoocataose I,
lacto-N-decaose, trifucosyllacto-N-neooctaose,
trifucosyllacto-N-octaose, trifucosyl-iso-lacto-N-octaose,
lacto-N-difuco-hexaose II, sialyl-lacto-N-tetraose a,
sialyl-lacto-N-tetraose b, sialyl-lacto-N-tetraose c,
sialyl-fucosyl-lacto-N-tetraose I, sialyl-fucosyl-lacto-N-tetraose
II, and disialyl-lacto-N-tetraose, and combinations thereof. Due to
acid stability, certain sialylated oligosaccharides (e.g.,
6'-sialyllactose) and fructooligosaccharides (FOS) may be less
preferred, but may still be included in certain exemplary
embodiments in accordance with the exemplary embodiments discussed
below.
[0033] Particularly suitable nutritional compositions include at
least one of the following HMOs: fucosylated oligosaccharides and
N-acetylated oligosaccharides. Specific non-limiting examples of
HMOs that are particularly suited for inclusion individually or in
combination in the exemplary nutritional compositions include:
2'-FL, 3'-FL, LNT, and LNnT.
[0034] 2'-FL is a soluble milk glycan present in human milk. 2'-FL
has been shown to be beneficial for the reduction of inflammation,
fighting infections, regulation of gastrointestinal contractions,
promotion of intestinal differentiation, as well as general
prebiotic properties. Many known ORTs do not properly address the
recovery of intestinal epithelium or the re-colonization of
beneficial gut flora. Provided herein are nutritional compositions
and oral rehydration compositions that address these unmet needs
via the novel inclusion of oligosaccharides. In certain exemplary
embodiments, the nutritional compositions address these needs via
the inclusion of shelf-stable HMOs such as 2'-FL.
[0035] In certain exemplary embodiments, the nutritional
compositions comprise a human milk oligosaccharide selected from a
fucosylated oligosaccharide and an N-acetylated oligosaccharide in
an amount of about 10 mg to about 5000 mg per liter of the
nutritional composition. In certain exemplary embodiments, the
human milk oligosaccharide is selected from 2'-fucosyllactose and
lacto-N-neotetraose. In certain exemplary embodiments, the
nutritional composition comprises 2'-fucosyllactose in an amount of
about 20 mg to about 4000 mg per liter of the nutritional
composition.
[0036] In addition to 2'-FL, other oligosaccharides may provide
similar benefits. In certain exemplary embodiments, the nutritional
composition further comprises a neutral human milk oligosaccharide.
Other human milk oligosaccharides suitable for inclusion in the
exemplary embodiments include fucosylated oligosaccharides and
N-acetylated oligosaccharides, and in particular 3'-fucosyllactose,
LNT, and LNnT. In certain exemplary embodiments, the neutral human
milk oligosaccharide is present in an amount of about 10 mg to
about 5000 mg per liter of the nutritional composition.
[0037] In certain embodiments, the nutritional compositions may
also include an oligosaccharide (also referred to as an
indigestible carbohydrate) or a source of an oligosaccharide
selected from GOS and xylooligosaccharides (XOS). In certain
exemplary embodiments, the nutritional compositions comprise an
indigestible oligosaccharide or a source of indigestible
oligosaccharide. In certain exemplary embodiments, the nutritional
compositions comprise GOS. GOS, also known as
oligogalactosyllactose, oligogalactose, oligolactose, or
transgalactooligosaccharides, is a known prebiotic oligosaccharide.
GOS is a polymer of lactose (a disaccharide itself), and most
sources of GOS comprise some inherent free lactose. This inherent
lactose poses a problem for use of GOS in a nutritional composition
intended for use to treat the symptoms of dehydration. Lactose is
known to exacerbate the symptoms of, for example, diarrhea, and
thus ingredients that include lactose are, as a rule, generally not
included in dehydration/rehydration therapies. Additional
non-limiting examples of indigestible carbohydrates include
oligofructose, inulin, polydextrose, hydrolyzed pectin, and
gums.
[0038] In certain exemplary embodiments, the nutritional
compositions comprise a digestible carbohydrate (or simply a
carbohydrate) or a source of digestible carbohydrate, in addition
to the oligosaccharides. The quantity of digestible carbohydrate
present in the nutritional compositions can vary depending upon the
needs of the ultimate user. In certain exemplary embodiments, the
nutritional composition comprises a digestible carbohydrate in an
amount of about 10 mM to about 150 mM of carbohydrate in the
nutritional composition. In certain exemplary embodiments, the
nutritional composition comprises a digestible carbohydrate in an
amount of about 50 mM to about 150 mM of carbohydrate in the
nutritional composition. Non-limiting examples of carbohydrates
suitable for use in the exemplary embodiments include dextrose,
maltodextrin, starch, isomaltulose, sucromalt, rice syrup, and rice
syrup solids. In certain exemplary embodiments, the digestible
carbohydrate comprises dextrose.
[0039] The amount of dextrose present in exemplary embodiments of
the nutritional composition may also be expressed in an amount of
dextrose in grams per liter. In certain exemplary embodiments,
dextrose is included in the nutritional composition in an amount
from about 1.8 g/L to about 60 g/L of the nutritional composition.
In certain exemplary embodiments, dextrose is present in an amount
from about 4.5 g/L to about 60 g/L. In certain exemplary
embodiments, dextrose is present in an amount from about 5 g/L to
about 60 g/L. In certain exemplary embodiments, dextrose is present
in an amount from about 10 g/L to about 10 g/L. In certain
exemplary embodiments, dextrose is present in an amount from about
5 g/L to about 30 g/L. In certain exemplary embodiments, dextrose
is present in an amount from about 10 g/L to about 25 g/L.
[0040] In certain exemplary embodiments, the nutritional
composition may also optionally include a source of digestible
carbohydrate other than dextrose. The carbohydrates may be simple
and/or complex carbohydrates, including monosaccharides,
disaccharides, oligosaccharides, and polysaccharides. Specific
examples of suitable carbohydrates include, but are not limited to
sucrose, fructose, dextrose polymers, corn syrup, high fructose
corn syrup, sucrose, lactose, maltose, amylose, glycogen,
galactose, allose, altrose, mannose, gulose, idose, talose, ribose,
arabinose, lyxose, ribose, xylose, erythrose, threose, and
combinations thereof.
[0041] In certain exemplary embodiments, the nutritional
composition comprises sodium. The sodium in the nutritional
compositions may be present as a cation of a salt. Examples of
suitable sodium sources include sodium chloride, sodium phosphate,
sodium citrate, sodium carbonate, sodium bicarbonate, sodium
hydroxide, sodium ascorbate, and combinations thereof.
[0042] The quantity of sodium ions present in the nutritional
composition varies widely and the ultimate amount may depend on the
needs of the particular user. In certain exemplary embodiments,
sodium is present in the nutritional composition in an amount of
about 10 mEq/L to about 100 mEq/L of the nutritional composition.
In certain exemplary embodiments, sodium is present in the
nutritional composition in an amount of about 10 mEq/L to about 95
mEq/L of the nutritional composition. In certain exemplary
embodiments, a sodium is present in an amount sufficient to provide
from about 15 mEq/L to about 95 mEq/L. In certain exemplary
embodiments, a sodium is present in an amount sufficient to provide
from about 25 mEq/L to about 95 mEq/L. In certain exemplary
embodiments, sodium is present in an amount sufficient to provide
from about 30 mEq/L to about 95 mEq/L. In certain exemplary
embodiments, sodium is present in the nutritional composition in an
amount of about 10 mEq/L to about 90 mEq/L of the nutritional
composition. In certain exemplary embodiments, sodium is present in
an amount sufficient to provide from about 45 mEq/L to about 90
mEq/L of the nutritional composition. In certain exemplary
embodiments, sodium is present in an amount sufficient to provide
from about 15 mEq/L to about 60 mEq/L of the nutritional
composition. In certain exemplary embodiments, sodium is present in
an amount sufficient to provide from about 45 mEq/L to about 60
mEq/L of the nutritional composition.
[0043] In addition to the oligosaccharides, dextrose, and sodium,
the nutritional compositions according to certain exemplary
embodiments may contain all the necessary electrolytes and levels
thereof required by the Food and Drug Administration for oral
rehydration formulations sold in the United States or recommended
by the World Health Organization for use globally.
[0044] In certain exemplary embodiments, the nutritional
composition further comprises citrate or a source of citrate. The
quantity of citrate present in the nutritional composition varies
widely and the ultimate amount may vary depending on the needs of
the particular user. Examples of suitable forms of citrate for
inclusion in the exemplary embodiments include potassium citrate,
sodium citrate and zinc citrate.
[0045] In certain exemplary embodiments, the nutritional
composition comprises citrate in an amount sufficient to provide
from about 1 mEq/L to about 200 mEq/L of the nutritional
composition. In certain exemplary embodiments, the nutritional
composition comprises citrate in an amount sufficient to provide
from about 1 mEq/L to about 180 mEq/L of the nutritional
composition. In certain exemplary embodiments, the nutritional
composition comprises citrate in an amount sufficient to provide
from about 1 mEq/L to about 160 mEq/L of the nutritional
composition. In certain exemplary embodiments, the nutritional
composition comprises citrate in an amount sufficient to provide
from about 1 mEq/L to about 140 mEq/L of the nutritional
composition. In certain exemplary embodiments, the nutritional
composition comprises citrate in an amount sufficient to provide
from about 1 mEq/L to about 130 mEq/L of the nutritional
composition. In certain exemplary embodiments, the nutritional
composition comprises citrate in an amount sufficient to provide
from about 3 mEq/L to about 200 mEq/L of the nutritional
composition. In certain exemplary embodiments, citrate is present
in an amount sufficient to provide from about 3 mEq/L to about 125
mEq/L of the nutritional composition. In certain exemplary
embodiments, citrate is present in an amount sufficient to provide
from about 3 mEq/L to about 100 mEq/L of the nutritional
composition. In certain exemplary embodiments, citrate is present
in an amount sufficient to provide from about 3 mEq/L to about 90
mEq/L of the nutritional composition. In certain exemplary
embodiments, citrate is present in an amount sufficient to provide
from about 3 mEq/L to about 75 mEq/L of the nutritional
composition. In certain exemplary embodiments, citrate is present
in an amount sufficient to provide from about 5 mEq/L to about 125
mEq/L of the nutritional composition. In certain exemplary
embodiments, citrate is present in an amount sufficient to provide
from about 8 mEq/L to about 125 mEq/L of the nutritional
composition. In certain exemplary embodiments, citrate is present
in an amount sufficient to provide from about 8 mEq/L to about 100
mEq/L of the nutritional composition. In certain exemplary
embodiments, citrate is present in an amount sufficient to provide
from about 8 mEq/L to about 50 mEq/L of the nutritional
composition. These amounts include citrates from any source,
including citric acid; citric ester that can be hydrolyzed into
citric acid or a citrate ion; or a citrate salt, such as potassium
citrate, sodium citrate, zinc citrate, and combinations
thereof.
[0046] In certain exemplary embodiments, the nutritional
composition comprises chloride or a source of chloride. The
chloride in an nutritional composition may be present as an ion in
the liquid, and may be in equilibrium with a salt. Examples of
suitable chloride salts include, but are not limited to sodium
chloride, potassium chloride, calcium chloride, magnesium chloride,
and combinations thereof. The amount of chloride present in the
nutritional composition may vary widely and the ultimate amount may
vary depending on the needs of the particular user. In certain
exemplary embodiments, the nutritional composition comprises
chloride in an amount from about 5 mEq/L to about 90 mEq/L of the
nutritional composition. In certain exemplary embodiments, the
nutritional composition comprises chloride in an amount from about
10 mEq/L to about 85 mEq/L of the nutritional composition. In
certain exemplary embodiments, the nutritional composition
comprises chloride in an amount from about 20 mEq/L to about 90
mEq/L of the nutritional composition. In certain exemplary
embodiments, the nutritional composition comprises chloride in an
amount from about 20 mEq/L to about 85 mEq/L of the nutritional
composition. In certain exemplary embodiments, the nutritional
composition comprises chloride in an amount from about 20 mEq/L to
about 80 mEq/L of the nutritional composition. In certain exemplary
embodiments, the nutritional composition comprises chloride in an
amount from about 15 mEq/L to about 80 mEq/L of the nutritional
composition.
[0047] In certain exemplary embodiments, the nutritional
composition may further comprise zinc or a source of zinc. The
source of zinc is generally not critical. Any zinc salt suitable
for human consumption may be used in the nutritional composition.
Examples of suitable zinc sources include zinc gluconate, zinc
sulfate, zinc chloride, zinc citrate, zinc bicarbonate, zinc
carbonate, zinc hydroxide, zinc lactate, zinc acetate, zinc
fluoride, zinc bromide, zinc sulfonate, and combinations thereof.
The amount of zinc used in the nutritional composition can vary
widely and the ultimate amount may vary depending on the needs of
the particular user. In certain exemplary embodiments, zinc is
present in the nutritional composition in an amount from about 0.1
mEq/L to about 95 mEq/L of the nutritional composition.
[0048] In certain exemplary embodiments, the nutritional
composition may further comprise potassium or a source of potassium
ions. The potassium in a nutritional composition may be present as
an ion in the liquid, and may be in equilibrium with a salt.
Examples of potassium salts include potassium chloride, potassium
phosphate, potassium citrate, potassium carbonate, potassium
bicarbonate, potassium hydroxide, and combinations thereof. The
quantity of potassium present in the nutritional composition can
vary widely and the ultimate amount may vary depending on the needs
of the particular user. In certain exemplary embodiments, potassium
is present in an amount sufficient to provide from about 3 mEq/L to
about 100 mEq/L of the nutritional composition. In certain
exemplary embodiments, potassium is present in an amount sufficient
to provide from about 5 mEq/L to about 100 mEq/L of the nutritional
composition. In certain exemplary embodiments, potassium is present
in an amount sufficient to provide from about 3 mEq/L to about 50
mEq/L of the nutritional composition. In certain exemplary
embodiments, potassium is present in an amount sufficient to
provide from about 10 mEq/L to about 50 mEq/L of the nutritional
composition. In certain exemplary embodiments, potassium is present
in an amount sufficient to provide from about 3 mEq/L to about 25
mEq/L of the nutritional composition. In certain exemplary
embodiments, a source of potassium is present in an amount
sufficient to provide from about 15 mEq/L to about 25 mEq/L of the
nutritional composition.
[0049] In certain exemplary embodiments, calcium or a calcium
containing substance may also be included in the nutritional
composition. Examples of suitable calcium containing substances
include calcium chloride, calcium oxide, calcium hydroxide, calcium
carbonate, calcium orthophosphate (including mono-, di- and
tricalcium phosphate), calcium lactate, calcium gluconate, calcium
citrate, calcium acetate, calcium ascorbate, calcium tartarate,
calcium malate and mixtures of these. The quantity of calcium
present in the nutritional composition can vary widely and the
ultimate amount may vary depending on the needs of the particular
user. In certain exemplary embodiments, calcium is present in an
amount sufficient to provide from about 0.25 mEq/L to about 30
mEq/L the nutritional composition. In certain exemplary
embodiments, calcium is present in an amount sufficient to provide
from about 0.25 mEq/L to about 20 mEq/L the nutritional
composition. In certain exemplary embodiments, calcium is present
in an amount sufficient to provide from about 0.4 mEq/L to about 20
mEq/L the nutritional composition. In certain exemplary
embodiments, calcium is present in an amount sufficient to provide
from about 15 mEq/L to about 20 mEq/L the nutritional
composition.
[0050] In certain exemplary embodiments, the nutritional
composition comprises at least one of protein and fat.
[0051] In certain exemplary embodiments, the nutritional
composition comprises protein from one or more sources. Suitable
sources of protein or sources thereof include, but are not limited
to, animal products (e.g., dairy proteins, meat, fish, egg
albumen), cereals (e.g., rice, corn), vegetables (e.g., soy, pea,
potato), and combinations thereof. Additional protein sources can
also include, peptides and free amino acids known for use in
nutritional compositions, non-limiting examples of which include
L-tryptophan, L-glutamine, L-tyrosine, L-methionine, L-cysteine,
L-arginine, L-threonine, L-serine, and combinations thereof.
[0052] In certain exemplary embodiments, the nutritional
composition comprises fat from one or more sources. Suitable
sources of fat or sources thereof include, but are not limited to,
coconut oil, fractionated coconut oil, soy oil, corn oil, olive
oil, safflower oil, high oleic safflower oil, MCT (medium chain
triglycerides) oil, sunflower oil, high oleic sunflower oil, palm
and palm kernel oils, palm olein, canola oil, marine oils,
cottonseed oils, non-dairy creamer, and combinations thereof.
[0053] In certain exemplary embodiments, the nutritional
composition further comprises a probiotic. In certain exemplary
embodiments, the probiotic is selected from the group of B.
animalis spp lactis BB-12, B. infintis ATCC15697, B. infantis M-63,
B. infantis 35624, B. lactis HNO19, B. lactis Bi07, L. rhaninosus
LGG, L. rhamnosus HN001, L. acidophilus LA-5, L. acidpohilus NCFM,
L. fermentum CECT5716, B. longum BB536, B. longum AH 1205, B. breve
M-16V, L. reuteri ATCC 55730, L. reuteri ATCC PTA-6475, L. reuteri
DSM 17938, and combinations thereof.
[0054] In certain exemplary embodiments, the nutritional
composition includes one or more additional ingredients. Examples
of additional ingredients for inclusion in the exemplary
embodiments include postbiotics (metabolites of prebiotics) long
chain polyunusaturated fatty acids (DHA, ARA, DPA, EPA, etc.),
nucleotides, antioxidant/anti-inflammatory compounds such as
tocopherols; carotenoids; ascorbate/vitamin C; ascorbyl palmitate;
polyphenols; glutathione; and superoxide dismutase, bioactive
factors (e.g., growth hormones, cytokines, antibodies, and
immunoglobulins), of human or bovine origin, tributyrin or other
SCFA-containing mono-, di-, or triglycerides, human milk derived
lipids, free amino acids or peptides (e.g., HMB, arginine, leucine,
and glutathione), lactose, other water- and fat-soluble vitamins,
minerals and trace elements. Further examples of additional
ingredients that may be used in exemplary embodiments include
flavorants, colorants, preservatives, excipients, gelling agents,
amino acids, calcium, vitamins, dietary supplements, and
combinations thereof. In general, the amount of any additional
ingredients in an nutritional composition is such that the primary
ingredients remain within the desired ranges.
[0055] In certain exemplary embodiments, a flavorant may be present
to add or modify a flavor in the nutritional composition, or to
enhance its palatability, especially in a pediatric population.
Examples of suitable flavorants include anise oil, cinnamon oil,
vanilla, vanillin, cocoa, chocolate, menthol, grape, fruit punch
flavoring, bubble gum flavoring, peppermint oil, oil of
wintergreen, clove oil, bay oil, anise oil, eucalyptus, thyme oil,
cedar leaf oil, oil of nutmeg, oil of sage, oil of bitter almonds,
cassia oil, citrus oils such as lemon, orange, lime and grapefruit
oils, and fruit essences, including apple, pear, peach, berry,
wildberry, date, blueberry, kiwi, strawberry, raspberry, cherry,
plum, pineapple, and apricot.
[0056] In certain exemplary embodiments, artificial sweeteners may
also be added to complement the flavor of the nutritional
composition. The concentration of sweetener in the nutritional
composition may be from about 0.01 to about 0.5 g/L of the
nutritional composition. Useful artificial sweeteners include
saccharin, nutrasweet, sucralose, aspartame, acesulfame-K (ace-K),
and the like.
[0057] In certain exemplary embodiments, a colorant may be present
to add or modify a color in the nutritional composition. Examples
of colorants include FD&C Red No. 3, FD&C Red No. 20,
FD&C Yellow No. 6, FD&C Blue No. 2, D&C Green No. 5,
FD&C Orange No. 5, D&C Red No. 8, caramel, ferric oxide,
pigments, dyes, tints, titanium dioxide, grape skin extract, beet
red powder, beta carotene, annato, carmine, turmeric, paprika, and
the like.
[0058] In certain exemplary embodiments, a preservative may be
present to provide a longer shelf life to a pre-packaged
nutritional composition, or to extend the potability lifetime of a
nutritional composition. Examples of suitable preservatives
include, but are not limited to, potassium sorbate and sodium
benzoate.
[0059] In certain exemplary embodiments, a gelling agent may be
present in the nutritional composition, such that the nutritional
composition can be formed into a gel, such as a flowable gel or a
self-supporting gel. Nutritional composition gels may provide
improved patient compliance in consuming a nutritional composition,
especially in a pediatric population. Gelled rehydration formulas
are described in U.S. Pat. No. 6,572,898, hereby incorporated by
reference herein. Gelling agents may be included in the nutritional
composition in amounts of from about 0.05 to about 50% (w/w).
[0060] The nutritional composition according to certain exemplary
embodiments can be manufactured using techniques well known to
those skilled in the art. For instance, the nutritional composition
may be prepared by combining the non-aqueous (i.e. "dry")
ingredients of the nutritional composition, for example by dry
blending, and dispersing the dry ingredients in a suitable amount
of water to provide a liquid having the appropriate concentrations
of ingredients, as set forth herein. Alternately, one or more of
the dry ingredients may be added separately to the water. The
nutritional composition may optionally be heated to the appropriate
temperature to dissolve all the ingredients, filtered, packaged,
and sterilized (sterilization may include heating, pasteurization,
radiation, an aseptic process, etc.) sterilization to food grade
standards as is known in the art.
[0061] The nutritional composition according to certain exemplary
embodiments may generally be heat sterilized either by a retort
process, an aseptic process, or a hot fill process.
[0062] A typical retort process involves introducing the
nutritional composition into a metal or plastic container, sealing
the container, and then heating the sealed container for a time
period and to a temperature sufficient for sterilization. Aseptic
sterilization involves separately sterilizing a metal or plastic
container and the nutritional composition, and then combining the
sterilized container and the nutritional composition in a clean
room environment and sealing the container. In a hot fill process,
the container is filled with the nutritional composition and sealed
at product temperatures above room temperature.
[0063] More specifically, in an exemplary retort sterilization
method, the nutritional composition is usually preheated and then
filled into a clean can, hermetically sealed, and placed in a steam
chamber and sterilized, at a temperature of about 100.degree. C.,
or in certain embodiments about 121.degree. C. for about 15 to
about 45 minutes. The batch is then cooled and the retort filled
with a new batch. Because sterilization takes place after filling,
the need for aseptic handling is eliminated, although heat
resistant plastic (or another heat resistant material) must be used
due to the high temperatures involved. In one specific retort
sterilization embodiment, a hydrostatic tower method is utilized
and includes conveying slowly the sealed containers through
successive heating and cooling zones in a sterilizer. The zones are
dimensioned to correspond to the required temperatures and holding
times in the various treatment stages.
[0064] In certain exemplary embodiments according to the aseptic
sterilization method, the nutritional composition is sterilized and
a container is separately sterilized. The nutritional composition
may be sterilized utilizing a heating process, for example. The
container may be sterilized by spraying the interior wall of the
container with hydrogen peroxide and then drying the interior wall.
Once the container and the nutritional composition have both been
sterilized, the nutritional composition is introduced into the
container in a clean room environment and the container sealed.
[0065] In certain exemplary embodiments, a hot fill processes alone
can be used to sterilize a high acid product (approximately below
pH 4.6). In hot fill sterilization, the container is filled with
the nutritional composition and the container is sealed at
approximately 180.degree. F. The filled container is then rotated
end-over-end so that the hot nutritional composition contacts all
surfaces and, finally, it is held hot for approximately five to ten
minutes to kill all viable microorganisms. Microorganisms which are
viable at low pH are molds and yeasts. If the product is a low acid
product, approximately above pH 4.6, the hot fill process does not
produce adequate sterility. Terminal sterilization is used to kill
harmful organisms potentially viable above pH 4.6. Terminal
sterilization kills potentially viable organisms by raising product
and container temperatures to the equivalent of 250.degree. F. for
a time equivalent to at least 3 minutes, more often, in excess of
10 minutes as determined using established practices to calculate
sterilization process time as a function of product temperature
history. The length of time the product and container are held at
an elevated temperature can be reduced markedly by using sterilizer
and product temperatures in excess of 250.degree. F. Sterilizer and
product temperatures well in excess of 250.degree. F. are commonly
used to reduce sterilization process time.
[0066] In certain exemplary embodiments, a nutritional composition
may be packaged in a container such as a glass or plastic bottle, a
plastic pouch, or a paper-based carton. In certain exemplary
embodiments, a nutritional composition may be formed by combining
water with the remaining nutritional composition ingredients,
agitating and/or heating the mixture to dissolve the ingredients,
and then packaging the nutritional composition in a container. The
nutritional composition may be sterilized before or after being
packaged, such as by retort, aseptic, or hot fill sterilization, as
discussed above. The nutritional composition may be packaged in a
container that includes an oxygen barrier, an oxygen scavenger,
and/or an ultraviolet radiation barrier. A single package of
nutritional composition may contain a single serving, such as 12
fl. oz. (0.35 L) or 1 L. A single package of nutritional
composition may contain multiple servings, such as multiples of 12
fl. oz. (0.35 L) or of 1 L.
[0067] In certain exemplary embodiments, a nutritional composition
may also be packaged in non-liquid forms, provided the nutritional
composition has undergone heat sterilization. In certain exemplary
embodiments, a nutritional composition may be packaged as a gel
containing one or more gelling agents as described above. In
certain exemplary embodiments, a nutritional composition may be
packaged as a frozen solution. Frozen nutritional compositions may
be in the form of ice cubes, ice on a stick (i.e. "freezer pop"),
crushed ice, or shaved ice, for example. Advantageously, frozen
nutritional composition may provide improved patient compliance,
particularly in pediatric populations. Frozen nutritional
compositions are disclosed, for example, in U.S. Pat. No.
5,869,459, hereby incorporated by reference herein.
[0068] Nutritional compositions according to the exemplary
embodiments may be administered in a variety of different forms,
depending upon patient preference. For example, some children will
consume a nutritional composition more readily if it is frozen,
like a freezer pop. The nutritional composition may be administered
as a frozen nutritional composition if the patient desires such a
choice. Other examples of suitable product forms are set forth
herein, such as powders and gels.
[0069] In certain exemplary embodiments, the nutritional
composition is an oral rehydration composition in the form of a gel
or frozen pop comprising sodium, potassium, chloride, a digestible
carbohydrate, and at least one human milk oligosaccharide selected
from a fucosylated oligosaccharide and a N-acetylated
oligosaccharide present in an amount of about 10 mg to about 5000
mg per liter of the oral rehydration composition.
[0070] In certain exemplary embodiments, the nutritional
composition is an oral rehydration composition in the form of a
reconstitutable powder and the at least one human milk
oligosaccharide is present in an amount of 0.2 to 13% by weight of
the powder.
[0071] In certain exemplary embodiments, the nutritional
composition may be used to prevent dehydration in an individual,
particularly in individuals suffering from fever. In certain
embodiments, an oral rehydration formula is prepared, and orally
administered to an individual at risk of developing
dehydration.
[0072] The total amount of calories provided by the nutritional
composition may vary widely. In certain exemplary embodiments, the
nutritional composition provides from about 10 kcal/L and 200
kcal/L. In certain exemplary embodiments, the nutritional
composition provides from about 30 kcal/L to about 150 kcal/L. In
certain exemplary embodiments, the nutritional composition provides
from about 50 kcal/L to about 100 kcal/L.
[0073] As mentioned previously, certain oligosaccharides are known
to have limited stability in acidic medium. This limited stability
is also known to decrease even further when subjected to heat while
in an acidic medium. Because of this, oligosaccharides are not
generally used in nutritional compositions with an acidic pH, such
as that in most compositions intended to treat or prevent
dehydration. However, provided herein are nutritional compositions
including oligosaccharides, such as fucosylated oligosaccharides
and N-acetylated oligosaccharides, with enhanced stability in
acidic medium.
EXAMPLES
[0074] The following examples illustrate certain exemplary
embodiments or features of the nutritional composition and methods
encompassed by the general inventive concepts. The examples are
given solely for the purpose of illustration and are not to be
construed as limitations of the present disclosure, as many
variations thereof are possible without departing from the spirit
and scope of the general inventive concepts.
[0075] A study was conducted to determine the relative stabilities
of GOS, FOS, 2'-FL, 6'-SL, and LNnT in an oral rehydration
solution. A master batch of product was prepared (shown in Table
1), the pH adjusted to approx. 4.25, and subsequently divided into
five sub-batches.
TABLE-US-00001 TABLE 1 Ingredient Amount per 1000 lb batch Water
983.4 lb Dextrose 8.5 lb Potassium citrate 1.042 kg Sodium chloride
0.970 kg Sodium citrate, dihydrate 0.511 kg Citric acid, anhydrous
1.222 kg
[0076] Oligosaccharide ingredients were added to each of the
sub-batches in amounts shown Table 2, and the pH of each sub-batch
was subsequently adjusted to 3.5 with citric acid. The solutions
were filled into 1 L plastic bottles, capped and retorted with a
cook temperature of 217.degree. F. for 25 minutes. Duplicate
samples were collected immediately prior to sterilization and
within 24 h after sterilization. Prior to sample analysis, the
unsterile samples were stored at refrigerated temperature
(.about.40.degree. F.) and the sterilized samples were held ambient
temperature.
TABLE-US-00002 TABLE 2 Oligosaccharide Target concentration in
product (g/L) GOS 3.20 FOS 3.20 2'FL 0.20 6'SL 0.20 LNnT 0.256
[0077] Samples were analyzed by HPAEC using a Dionex ICS3000 Ion
Chromatography System (Thermo Scientific, Inc., Sunnyvale, Calif.)
equipped with a pulsed amperometric detector comprised of a AgCl
reference electrode, gold working electrode, and CarboPac PA1 guard
(4.times.50 mm) and analytical columns (4.times.250 mm). Mobile
phases were degassed and pressurized with 3 to 5 psi helium, and
oligosaccharides eluted from the columns using various gradients
detailed in Tables 3-5 at a flow rate of 1.0 mL/min. The column and
detector were held at 20.+-.2.degree. C. Oligosaccharide
identification and concentration were determined from quadratic fit
(not forced through the origin) standard curves.
[0078] Table 3 shows an exemplary chromatography gradient used for
analysis of GOS, wherein Eluent 1=Laboratory Water, Eluent 2=50 mM
Sodium Acetate, Eluent 3=500 mM Sodium Hydroxide, and Eluent 4=300
mM Sodium Acetate.
TABLE-US-00003 TABLE 3 Time (min) % 1 % 2 % 3 % 4 0.0 90 6 4 0 26.0
90 6 4 0 26.1 16.7 0 0 83.3 29.0 16.7 0 0 83.3 29.1 60 0 40 0 32.0
60 0 40 0 32.1 90 6 4 0 46.0 90 6 4 0
[0079] Table 4 shows an exemplary chromatography gradient used for
analysis of FOS, wherein Eluent 1=Laboratory Water, Eluent 2=Not
Used, Eluent 3=500 mM Sodium Hydroxide, and Eluent 4=300 mM Sodium
Acetate.
TABLE-US-00004 TABLE 4 Time (min) % 1 % 2 % 3 % 4 0.0 80 0 20 0 2.0
80 0 20 0 2.1 76 0 20 4 25.0 48 0 20 32 25.1 0 0 20 80 35.1 0 0 20
80 35.2 80 0 20 0 60.0 80 0 20 0
[0080] Table 5 shows an exemplary chromatography gradient used for
analysis of HMO's, wherein Eluent 1=Laboratory Water, Eluent 2=Not
Used, Eluent 3=500 mM Sodium Hydroxide, Eluent 4=300 mM Sodium
Acetate.
TABLE-US-00005 TABLE 5 Time (min) % 1 % 2 % 3 % 4 0.0 80 0 20 0
10.0 80 0 20 0 18.0 70 0 20 10 28.0 70 0 20 10 32.0 48 0 20 32 39.0
48 0 20 32 39.01 0 0 20 80 43.0 0 0 20 80 43.01 80 0 20 0 50.0 80 0
20 0
[0081] Table 6 shows the results of testing the sample prepared
with GOS both before (unsterile) and after sterilization (sterile),
as well as 3-weeks after sterilization (3-week). GOS fortification
was calculated to be 3.19 g/L. Galactooligosaccharide content was
based upon the determination of the enzymatically released
galactose from the GOS oligomers. The samples were enzymatically
treated with .beta.-galactosidase (pH 6.0 at 60.degree. C. for 1 h)
in order to hydrolyze the GOS oligomers to galactose and glucose
(note GOS content is calculated from galactose only). Based on the
results in Table 6, there appears to be minimal loss of GOS during
a retort process. Additionally, there is also no loss relative to
the sterilized sample 3-weeks after sterilization.
TABLE-US-00006 TABLE 6 Galactose Lactose GOS % Theoretical Sample
g/L g/L g/L GOS Unsterile 1 0.0670 0.767 3.09 97 Unsterile 2 0.0667
0.769 3.14 98.5 Average 0.0668 0.768 3.12 97.8 Sterile 1 0.0679
0.754 3.08 96.7 Sterile 2 0.0689 0.764 3.10 97.3 Average 0.0684
0.759 3.09 97 3-week 1 0.0679 0.0754 3.08 96.7 3-week 2 0.0689
0.0764 3.10 97.3 Average 0.0684 0.0759 3.09 97
[0082] Table 7 shows the results of testing the sample prepared
with FOS both before (unsterile) and after sterilization (sterile),
as well as 3-weeks after sterilization (3-week). FOS fortification
was calculated to be 3.2 g/L. Testing samples were reconstituted at
10 mL to 500 mL with water, and then filtered using a 0.2 .mu.m PES
membrane syringe filter. Fructooligosaccharide content was
determined from the levels of GF.sub.2 (1-kestose), GF.sub.3
(nystose), and GF.sub.4 (1-fructofuranosylnystose) in commodity and
product and then applying the following formula: FOS in
product=(GF.sub.2+GF.sub.3+GF.sub.4).sub.product*(potency of FOS
commodity/[GF.sub.2+GF.sub.3+GF.sub.4].sub.commodity). FOS has a
loss of approximately 88% during sterilization, with continued loss
over 3-weeks.
TABLE-US-00007 TABLE 7 GF2 GF3 GF4 FOS % Theoretical Sample g/L g/L
g/L g/L FOS Unsterile 1 1.14952 1.4819 0.2680 3.25 101.6 Unsterile
2 1.14636 1.4738 0.2664 3.24 101.2 Average 1.14794 1.4778 0.2672
3.24 101 Sterile 1 0.19958 0.1220 0.0123 0.374 11.70 Sterile 2
0.19907 0.1219 0.0130 0.375 11.71 Average 0.199325 0.12196 0.01264
0.375 11.7 3-week 1 0.18267 0.1156 0.0118 0.3477 10.87 3-week 2
0.18309 0.1144 0.0121 0.3471 10.85 Average 0.18288 0.114985 0.01192
0.347 10.9
[0083] Table 8 shows the results of testing the sample prepared
with 2'-FL both before (unsterile) and after sterilization
(sterile), as well as 3-weeks after sterilization (3-week). 2'-FL
fortification was calculated to be 0.2 g/L. Testing samples were
reconstituted at 20 mL to 100 mL with water, and then filtered
using a 0.2 .mu.m PES membrane syringe filter. 2'-FL shows a slight
decrease after sterilization, however, there is no further loss
observed after 3-weeks.
TABLE-US-00008 TABLE 8 Lactose Lactulose 2'-FL % Theoretical Sample
mg/L mg/L mg/L 2'-FL Unsterile 1 13.94 NAP 200.8 100.4 Unsterile 2
14.43 NAP 202.1 101.0 Average 14.2 NAP 201 101 Sterile 1 14.5 3.401
194.8 97.38 Sterile 2 14.33 2.617 196.7 98.35 Average 14.4 3.01 196
97.9 3-week 1 15.59 3.25 196.6 98.31 3-week 2 15.01 2.792 196.8
98.38 Average 15.3 3.02 197 98.3
[0084] Table 9 shows the results of testing the sample prepared
with LNnT both before (unsterile) and after sterilization
(sterile), as well as 3-weeks after sterilization (3-week). LNnT
fortification was calculated to be 0.256 g/L. Testing samples were
reconstituted at 20 mL to 100 mL with water, and then filtered
using a 0.2 m PES membrane syringe filter. As can be seen from the
table, LNnT shows a no decrease after sterilization. Additionally
there is no further loss of LNnT observed after 3-weeks.
TABLE-US-00009 TABLE 9 Sample Lactose mg/L LNnT mg/L % Theoretical
LNnT Unsterile 1 25.78 257.6 100.7 Unsterile 2 25.46 259.4 101.4
Average 25.6 258 101 Sterile 1 26.34 261 102.1 Sterile 2 27.26
261.1 102.1 Average 26.8 261 102 3-week 1 28.03 266.5 104.2 3-week
2 28.19 271.0 106 Average 28.1 269 105
[0085] Table 10 shows the results of testing the sample prepared
with 6'-SL both before (unsterile) and after sterilization
(sterile), as well as 3-weeks after sterilization (3-week). 6'-SL
fortification was calculated to be 0.2 g/L. Testing samples were
reconstituted at 20 mL to 100 mL with water, and then filtered
using a 0.2 .mu.m PES membrane syringe filter. Significant loss of
6'-SL was observed upon sterilization. No additional loss of 6'-SL
was observed after 3-weeks.
TABLE-US-00010 TABLE 10 Lactose Sialic Acid 6'-SL % Theoretical
Sample mg/L mg/L mg/L 6'-SL Unsterile 1 24.22 5.055 170.8 85.42
Unsterile 2 24.90 4.842 174.5 87.24 Average 24.6 4.95 173 86.3
Sterile 1 149.4 83.46 10.39 5.195 Sterile 2 149.4 83.79 11.0 5.502
Average 149 83.6 10.7 5.35 3-week 1 152.2 82.89 10.5 5.249 3-week 2
154 82.96 10.6 5.3 Average 153 82.9 10.5 5.27
[0086] As can be seen from the tables, GOS, 2'-FL, and LNnT
demonstrated enhanced stability in the exemplary formulations,
especially in comparison to the relative stability of FOS and
6'-SL. Therefore, nutritional compositions comprising fucosylated
oligosaccharide, N-acetylated oligosaccharide and combinations
thereof, would be expected to demonstrate shelf stability even
after a heat sterilization process.
[0087] Table 11 is a listing of ingredients for a liquid
nutritional composition (in the form of an ORC) having an acidic
pH, a fruit flavor, and comprising a human milk oligosaccharide
according to certain exemplary embodiments disclosed herein.
TABLE-US-00011 TABLE 11 Ingredient Amount per 1000 kg batch Kg/g/mg
Water Q.S. Dextrose monohydrate 27.67 Kg Citric acid 2.7 Kg Flavor
2.503 Kg Potassium Citrate 2.3 Kg Sodium Chloride 2.140 Kg Sodium
Citrate 1.129 Kg Sucralose 395.3 g Acesulfame Potassium 83.99 g
Zinc Gluconate 63.70 g 2'-fucosyllactose 20.00 g Color 20.00 g
[0088] Table 12 is a listing of ingredients for a liquid
nutritional composition (in the form of an ORC) having an acidic
pH, a fruit flavor, and comprising a human milk oligosaccharide and
an indigestible oligosaccharide according to certain exemplary
embodiments disclosed herein.
TABLE-US-00012 TABLE 12 Ingredient Amount per 1000 kg batch Kg/g/mg
Water Q.S. Dextrose monohydrate 17.9 Kg Galacto-oligosaccharides
6.3 Kg Citric acid 2.7 Kg Flavor 2.5 Kg Potassium Citrate 2.3 Kg
Sodium Chloride 2.1 Kg Sodium Citrate 1.1 Kg Sucralose 395.3 g
Acesulfame Potassium 84 g Zinc Gluconate 63.7 g 2'-fucosyllactose
20.0 g Color 16.0 g
[0089] Table 13 is a listing of ingredients for a nutritional
composition in the form of a frozen pop having an acidic pH, a
fruit flavor, and comprising a human milk oligosaccharide and an
indigestible oligosaccharide according to certain exemplary
embodiments disclosed herein.
TABLE-US-00013 TABLE 13 Ingredient Amount per 1000 kg batch Kg/g/mg
Water Q.S. Dextrose 25.5 Kg Citric acid 5.2 Kg Sodium Chloride 2.1
Kg Sodium Carboxy-methyl 2.0 Kg cellulose Potassium Citrate 1.9 Kg
monohydrate Potassium sorbate 513 g Sodium benzoate 500 g Flavor
500 g Sucralose 198 g Acesulfame Potassium 148 g 2'-fucosyllactose
20 g Color 11.00 g
[0090] Another study was performed to determine the stability of
2'-FL, LNnT, and 6'-SL in an ORC over time (e.g., 1 week, 3 weeks,
6 weeks, and 14 weeks).
[0091] Sample Preparation: A master batch with a pH of 4.25 is
sub-divided. The oligosaccharides are added to the respective ORC
in an amount of 0.2 g/L for 2'-FL and 6'-SL, LNnT was fortified in
an amount of 0.256 g/L. The pH was then adjusted from 4.25 to 3.5
by addition of citric acid. Prior to sterilization, samples are
collected to evaluate oligosaccharide levels. The formulas were
then delivered into 1 L bottles and subjected to heat sterilization
and allowed to cool to room temperature.
[0092] Initial Time Analysis: total solids, sodium, potassium,
chloride and pH are measured and the results are shown in Table
14.
TABLE-US-00014 TABLE 14 Assay 2'-FL 6'-SL LNnT Total solids 2.04
1.93 1.94 pH 3.44 3.46 3.46 Chloride mg/kg 1330 1330 1330 Potassium
mg/100 g 83.5 83.7 83.2 Sodium mg/100 g 111 111 111
[0093] Table 15 shows the results of sample measurements
determining the levels of 2'-FL (mg/L), lactose (mg/L), and
lactulose (mg/L), as determined at 0 days, 3 weeks, 6 weeks, and 14
weeks. The data on day 0 was collected in duplicate for samples
prior to sterilization (unsterile) and after sterilization
(sterile), thereafter the data was collected only on the sterilized
samples. 2'-FL shows very little change over the course of the
study. The slight fluctuation in lactose and lactulose levels are
likely due to method variability.
TABLE-US-00015 TABLE 15 Intervals 0 D 3 WK 6 WK 14 WK % % % % Assay
Sample mg/L Remaining * mg/L Remaining ** mg/L Remaining ** mg/L
Remaining ** 2'-FL Unsterile 1 200.8 100.4% NAP NAP NAP NAP NAP NAP
mg/L Unsterile 2 202.1 .sup. 101% NAP NAP NAP NAP NAP NAP Average
201 .sup. 101% NAP NAP NAP NAP NAP NAP Sterile 1 194.8 97.38% 196.6
98.31% 197.7 98.83% 201.2 100.6% Sterile 2 196.7 98.35% 196.8
98.38% 200.3 100.2% 200.8 100.4% Average 196 97.9% 197 98.30% 199
99.5% 201 .sup. 101% Lactose Unsterile 1 13.94 NAP NAP NAP NAP NAP
NAP NAP mg/L Unsterile 2 14.43 NAP NAP NAP NAP NAP NAP NAP Average
14.2 NAP NAP NAP NAP NAP NAP NAP Sterile 1 14.5 NAP 15.59 NAP 15.35
NAP 15.05 NAP Sterile 2 14.33 NAP 15.01 NAP 14.77 NAP 15.4 NAP
Average 14.4 NAP 15.30 NAP 15.1 NAP 15.2 NAP Lactulose Unsterile 1
NAP NAP NAP NAP NAP NAP NAP NAP mg/L Unsterile 2 NAP NAP NAP NAP
NAP NAP NAP NAP Average NAP NAP NAP NAP NAP NAP NAP NAP Sterile 1
3.401 NAP 3.25 NAP 3.103 NAP 2.445 NAP Sterile 2 2.617 NAP 2.792
NAP 2.644 NAP 2.937 NAP Average 3.01 NAP 3.02 NAP 2.870 NAP 2.690
NAP * % Remaining denotes the % loss or % increase for results
calculated comparing the average results for unsterile to average
sterile results to the target fortification. The assumed target
fortification for 2'-FL is 200 mg/L. ** % Remaining denotes % loss
or % increase of 3, 6, and 14 weeks test results and is calculated
comparing the average interval results to the average 0 D
results.
[0094] Table 16 shows the results of sample measurements
determining the levels of LNnT (mg/L) and % remaining, as
determined at 0 days, 3 weeks, 6 weeks, and 14 weeks. The data on
day 0 was collected in duplicate for samples prior to sterilization
(unsterile) and after sterilization (sterile), thereafter the data
was collected only on the sterilized samples. No substantial loss
of LNnT was observed during the test period.
TABLE-US-00016 TABLE 16 Intervals 0 D 3 WK 6 WK 14 WK % % % % Assay
Sample mg/L Remaining * mg/L Remaining ** mg/L Remaining ** mg/L
Remaining ** LNnT Unsterile 1 257.6 100.7% NAP NAP NAP NAP NAP NAP
mg/L Unsterile 2 259.4 101.4% NAP NAP NAP NAP NAP NAP Average 258
.sup. 101% NAP NAP NAP NAP NAP NAP Sterile 1 261 102.1% 266.5
104.2%.sup. 265.8 103.9% 272.7 106.6% Sterile 2 261.1 102.1% 271.0
106% 268.4 104.9% 264.3 103.4% Average 261 .sup. 102% 269 105% 267
.sup. 104% 269 .sup. 105% Lactose Unsterile 1 25.78 NAP NAP NAP NAP
NAP NAP NAP mg/L Unsterile 2 25.46 NAP NAP NAP NAP NAP NAP NAP
Average 25.6 NAP NAP NAP NAP NAP NAP NAP Sterile 1 26.34 NAP 28.03
NAP 30.89 NAP 27.94 NAP Sterile 2 27.26 NAP 28.19 NAP 28.6 NAP
28.14 NAP Average 26.8 NAP 28.10 NAP 29.7 NAP 28 NAP * % Remaining
denotes the % loss or % increase for results calculated comparing
the average results for unsterile to average sterile results to the
target fortification. The assumed target fortification for 2'-FL is
200 mg/L. ** % Remaining denotes % loss or % increase of 3, 6, and
14 weeks test results and is calculated comparing the average
interval results to the average 0 D results.
[0095] Table 17 shows the results of sample measurements
determining the levels of 6'-SL (mg/L), Lactose (mg/L), and Sialic
acid (mg/L) and % remaining, as determined at 0 days, 3 weeks, 6
weeks, and 14 weeks. The data on day 0 was collected in duplicate
for samples prior to sterilization (unsterile) and after
sterilization (sterile), thereafter the data was collected only on
the sterilized samples. A significant decrease in 6'-S levels was
observed post sterilization and throughout the testing intervals.
At 14 weeks, the concentration was 2.3% of the target fortification
amount. Slight discoloration was observed relative to the other
test compositions.
TABLE-US-00017 TABLE 17 Intervals 0 D 3 WK 6 WK 14 WK % % % % Assay
Sample mg/L Remaining * mg/L Remaining ** mg/L Remaining ** mg/L
Remaining ** 6'-SL Unsterile 1 170.8 85.42% NAP NAP NAP NAP NAP NAP
mg/L Unsterile 2 174.5 87.24% NAP NAP NAP NAP NAP NAP Average 173
86.3% NAP NAP NAP NAP NAP NAP Sterile 1 10.39 5.195% 10.5 5.249%
10.47 5.234% 4.66 2.330% Sterile 2 11 5.502% 10.6 5.3% 10.59 5.295%
4.57 2.285% Average 10.7 5.35% 10.5 5.27% 10.5 5.26% 4.6 2.31%
Lactose Unsterile 1 24.22 NAP NAP NAP NAP NAP NAP NAP mg/L
Unsterile 2 24.9 NAP NAP NAP NAP NAP NAP NAP Average 24.6 NAP NAP
NAP NAP NAP NAP NAP Sterile 1 149.4 NAP 152.2 NAP 170.5 NAP 149.5
NAP Sterile 2 149.4 NAP 154.0 NAP 174.4 NAP 155.1 NAP Average 149
NAP 153 NAP 172 NAP 152 NAP Sialic Unsterile 1 5.055 NAP NAP NAP
NAP NAP NAP NAP acid Unsterile 2 4.842 NAP NAP NAP NAP NAP NAP NAP
mg/L Average 4.95 NAP NAP NAP NAP NAP NAP NAP Sterile 1 83.46 NAP
82.89 NAP 98.77 NAP 91.10 NAP Sterile 2 83.79 NAP 82.96 NAP 97.2
NAP 92.22 NAP Average 83.6 NAP 82.9 NAP 98 NAP 91.7 NAP * %
Remaining denotes the % loss or % increase for results calculated
comparing the average results for unsterile to average sterile
results to the target fortification. The assumed target
fortification for 2'-FL is 200 mg/L. ** % Remaining denotes % loss
or % increase of 3, 6, and 14 weeks test results and is calculated
comparing the average interval results to the average 0 D
results.
[0096] While the general inventive concepts have been illustrated
by the description of various exemplary embodiments, and while the
exemplary embodiments have been described in considerable detail,
it is not the intention of the applicants to restrict or in any way
limit the scope of the general inventive concepts or the appended
claims to such detail. Additional advantages and modifications will
readily appear to those skilled in the art. Therefore, the general
inventive concepts are not limited to the specific details, the
representative compositions and processes, and illustrative
examples shown and described. Accordingly, departures may be made
from such details without departing from the spirit or scope of the
general inventive concepts.
* * * * *