U.S. patent application number 11/573939 was filed with the patent office on 2008-05-29 for infant formula.
This patent application is currently assigned to N.V. NUTRICA. Invention is credited to Christopher Beermann, Gunther Boehm, Bernd Stahl.
Application Number | 20080125346 11/573939 |
Document ID | / |
Family ID | 34926246 |
Filed Date | 2008-05-29 |
United States Patent
Application |
20080125346 |
Kind Code |
A1 |
Beermann; Christopher ; et
al. |
May 29, 2008 |
Infant Formula
Abstract
The present invention relates to a nutritional composition
containing protein, fat and carbohydrate; and a. a nucleotide
component selected from the group consisting of nucleic acid,
nucleic acid derivatives, nucleotides, nucleoside polyphosphates,
polynucleotides, nucleosides, ribose, desoxyribose, and
dinucleosidpolyphosphates (Np.sub.xN); and b. a non-proteinaceous
negatively charged, glycan or glycoconjugate component with a
molecular weight between 200 and 20.000 dalton. The present
nutritional composition is particularly suited for feeding infants
as it mimics the protective effects of human milk, in particular
against allergies and infections.
Inventors: |
Beermann; Christopher;
(Neu-Anspach, DE) ; Boehm; Gunther; (Echzell,
DE) ; Stahl; Bernd; (Rosbach-Rodheim, DE) |
Correspondence
Address: |
FOLEY AND LARDNER LLP;SUITE 500
3000 K STREET NW
WASHINGTON
DC
20007
US
|
Assignee: |
N.V. NUTRICA
|
Family ID: |
34926246 |
Appl. No.: |
11/573939 |
Filed: |
August 22, 2005 |
PCT Filed: |
August 22, 2005 |
PCT NO: |
PCT/NL05/00609 |
371 Date: |
November 12, 2007 |
Current U.S.
Class: |
424/439 ;
514/18.7; 514/5.5 |
Current CPC
Class: |
A23V 2002/00 20130101;
A23L 33/12 20160801; A61P 37/02 20180101; A61P 29/00 20180101; A23V
2002/00 20130101; A61P 1/12 20180101; A61P 31/04 20180101; A61P
3/02 20180101; A61P 17/02 20180101; A61K 31/702 20130101; A23L
33/22 20160801; A23V 2250/28 20130101; A61P 37/08 20180101; A61K
31/715 20130101; A61K 31/7052 20130101; A61P 1/00 20180101; A61P
17/00 20180101; A23V 2250/5046 20130101; A23V 2250/1868 20130101;
A23V 2250/1872 20130101; A23V 2250/1862 20130101; A23V 2250/1874
20130101; A23V 2250/187 20130101; A61P 43/00 20180101; A23V
2250/5072 20130101; A23L 33/40 20160801; A61K 31/201 20130101; A61P
37/04 20180101; A23L 33/19 20160801 |
Class at
Publication: |
514/2 |
International
Class: |
A61K 38/00 20060101
A61K038/00; A61P 37/08 20060101 A61P037/08; A61P 1/12 20060101
A61P001/12; A61P 17/00 20060101 A61P017/00; A61P 29/00 20060101
A61P029/00 |
Foreign Application Data
Date |
Code |
Application Number |
Aug 20, 2004 |
EP |
04019856.6 |
Claims
1-14. (canceled)
15. A nutritional composition comprising a. a protein, b. a fat, c.
a carbohydrate; d. a nucleotide component selected from the group
consisting of nucleic acid, nucleic acid derivatives, nucleotides,
nucleoside polyphosphates, polynucleotides, nucleosides, ribose,
desoxyribose, and dinucleosidpolyphosphates; and e. a
non-proteinaceous, negatively charged, glycan or glycoconjugate
component with a molecular weight between 200 and 20,000
Dalton.
16. The nutritional composition according to claim 15, wherein the
glycan or glycoconjugate component has a molecular weight between
1,000 and 10,000 Dalton.
17. The nutritional composition according to claim 15, comprising 5
to 15 energy % protein; 30 to 60 energy % fat; and 25 to 65 energy
% carbohydrate.
18. The nutritional composition according to claim 15, comprising,
per 100 gram dry weight of the composition, between 5 and 100 mg
nucleotides; between 5 and 100 mg nucleosides; or both.
19. The nutritional composition according to claim 15, wherein the
nucleotide component is ribose.
20. The nutritional composition according to claim 18, wherein the
nucleotide component is ribose.
21. The nutritional composition according to claim 15 further
comprising between 150 and 1000 mg calcium; 2 to 100 mg zinc; or
both.
22. The nutritional composition according to claim 15 wherein the
negatively charged glycan or glycoconjugate component comprises
acidic oligosaccharides, acid gangliosides, or both.
23. The nutritional composition according to claim 22, wherein the
negatively charged glycan or glycoconjugate component is a
polygalacturonic acid with a DP between 2 and 100.
24. The nutritional composition according to claim 23, wherein the
polygalacturonic acid is pectin hydrolysate.
25. The nutritional composition according to claim 8, wherein the
negatively charged glycan or glycoconjugate component is a
ganglioside.
26. A method for providing nutrition to an infant, said method
comprising administering to the infant a nutritional composition
comprising a. a protein, b. a fat, c. a carbohydrate; d. a
nucleotide component selected from the group consisting of nucleic
acid, nucleic acid derivatives, nucleotides, nucleoside
polyphosphates, polynucleotides, nucleosides, ribose, desoxyribose,
and dinucleosidpolyphosphates; and e. a non-proteinaceous,
negatively charged, glycan or glycoconjugate component with a
molecular weight between 200 and 20,000 Dalton.
27. A method of treatment and/or prevention of an inflammatory
disease, diarrhea, eczema and/or atopic dermatitis, comprising
administering to the mammal a nutritional composition comprising a.
a protein, b. a fat, c. a carbohydrate; d. a nucleotide component
selected from the group consisting of nucleic acid, nucleic acid
derivatives, nucleotides, nucleoside polyphosphates,
polynucleotides, nucleosides, ribose, desoxyribose, and
dinucleosidpolyphosphates; and e. a non-proteinaceous, negatively
charged, glycan or glycoconjugate component with a molecular weight
between 200 and 20,000 Dalton.
28. The method according to claim 27, wherein the inflammatory
disease is allergy.
29. The method according to claim 28, wherein the mammal is a
human.
30. The method according to claim 29, wherein the human is an
infant.
Description
FIELD OF THE INVENTION
[0001] The present invention relates to a nutritional composition
for feeding infants, containing fat, protein, carbohydrate, a
nucleotide component and to the use thereof.
BACKGROUND OF THE INVENTION
[0002] Breastfeeding optimally supports the development of the
infant and protects against infections and allergies. However, not
all infants are in the position to receive human milk. It is
therefore a continuing aim to provide infant formula, which
simulates the functions of human milk. In addition to the desired
compositional similarity between infant formula and human milk, it
is also particularly desirable to mimic the protective effects of
human milk, in particular protection against allergies and
infections.
SUMMARY OF THE INVENTION
[0003] The present inventors have recognized that the molecular
structure and density of charge of nucleotides is an important
factor for the bioactivity of nucleotide components, particularly
nucleotides. It was found that by combining nucleotide components
with negatively charged non-protein components the bioactive
effects of the nucleotide component in nutritional formulations may
be enhanced significantly.
[0004] Hence, the present invention provides a nutritional
composition containing a nucleotide component; and a
non-proteinaceous negatively charged, glycan or glycoconjugate
component with a molecular weight between 200 and 20.000 dalton
(hereinafter referred to as NCC).
[0005] The present nutritional composition is particularly
effective in: [0006] Enhancing immune cell proliferation, improving
the development of T-lymphocyte sub populations, and enhancing the
antibody response; [0007] Stimulating the development of the immune
system of neonates [0008] Stimulating the development of the nerve
system of neonates [0009] Stimulating the neonatal development and
repair of the gastrointestinal tract after surgery or disease
[0010] Modulating the gutflora, Stimulating the synthesis of
long-chain polyunsaturated fatty acids [0011] Providing
anti-infective, antibacterial/viral effects
[0012] Without wishing to be bound by theory, the improved activity
is believed to be the result of an improved presentation and
delivery of the negatively charged nucleotide component to the
epithelial cells, due to interaction of the NCC and the nucleotide
component e.g. via hydrogen and salt bridges. The biological active
molecular anionic charge of nucleotides is condensed and the
molecular distribution of charge is beneficially altered.
[0013] The present nutritional composition can be even further
improved by combining the nucleotide component and NCC with
bivalent cations, preferably calcium and/or zinc. The cation will
increase proximity of the nucleotide component and the NCC in a
liquid environment (e.g. the intestinal tract) by formation of
hydrogen/salt bridges, thereby further increasing the interactive
effects between the NCC and the nucleotide components.
DETAILED DESCRIPTION
[0014] The present invention provides a nutritional composition
containing protein, fat and carbohydrate; and a nucleotide
component selected from the group consisting of nucleic acid,
nucleic acid derivatives, nucleotides, nucleoside polyphosphates,
polynucleotides, nucleosides, ribose, desoxyribose, and
dinucleosidpolyphosphates (Np.sub.xN); and a non-proteinaceous
negatively charged, glycan or glycoconjugate component with a
molecular weight between 200 and 20.000 dalton
Nucleotide Component
[0015] The present composition contains a nucleotide component
selected from the group consisting of nucleic acid, nucleic acid
derivatives, nucleotides, nucleoside polyphosphates,
polynucleotides, nucleosides, ribose, desoxyribose, and
dinucleosidpolyphosphates (Np.sub.xN).
[0016] Nucleic acids are typically heterocyclic pyrimidine bases
cytosine, thymine, uridine and derivatives, like pseudouridine,
dihyderouridine, ribothymidine, 4-thiouridine, 3-methylcytidine,
N-acetylcytidine, lysidine as well as purine bases adenine and
guanosine and derivatives, like 1-methyladenosine,
N6-isopentenyladenosine, inosine, N7-methylguansine,
N2-dimethylguano sine and wyosine. Nucleosides such as N-glycoside
are pyrimidine or purine base glycoconjugates. Preferred
nucleotides are phosphoesters of nucleosides, which are monomers or
polymers in the form of oligo- or polynucleotides. For this
application especially hydrolysates of desoxyribonucleic acid and
ribonucleic acid, t-ribonucleic acid and ribosomes derived from
animal milk, animal and plant tissues, yeasts, bifido- and
lactobacteria and synthetic molecules are suitable raw material
sources. ( Biochemistry, Donald Voet and Judith G. Voet, John Wiley
and Sons, Inc NY second edition chapter 28, pp 849)
[0017] Preferably, the present composition contains at least one,
preferably at least two, even more preferably at least three
nucleotides selected from the group consisting of cytidine
monophosphate (CMP), guanosine monophosphate (GMP), adenosine
monophosphate (AMP), uridine monophosphate (UMP), and inosine
monophosphate (IMP).
[0018] In a further preferred embodiment the present composition
contains ribose as a nucleotide component, preferably D-ribose.
D(-)Ribose is a pentose sugar that can be purchased as crystalline
product. Ribose is a main constituent of nucleic acids. Preferably
the present composition contains between 0.01 wt. % and 50 wt. %
ribose based on dry weight of the product, more preferably between
0.05 and 10 wt. %, even more prefferably between 0.5 and 10 wt.
%
[0019] The present composition preferably comprises between 5 and
100 mg nucleosides and/or between 5 and 100 mg nucleotides per 100
gram dry weight of the composition, more preferably between 5 and
50 mg. The nucleotides and/or nucleosides further stimulate the
immune system, acting synergistically with the NCC of the present
composition.
Negatively Charged Component (NCC)
[0020] The present composition contains a negatively charged
non-proteineous glycan and glycoconjugate component (NCC) with a
molecular weight between 200 and 20.000 dalton.
[0021] The NCC is negatively charged in water with a pH of 7. The
negative charge is preferably provided by a carboxylic, phosphate
and/or sulphate group, most preferably by a carboxylic group.
Preferably the NCC has a MW between 1000 and 10.000 Dalton. The
weight ratio nucleotide component/NCC in the present nutritional
composition is preferably between 100 and 0.1.
[0022] Preferably the NCC is selected from the group consisting of
glycosphingolipids, acid oligosaccharides, and sialysated
oligosaccharides. Preferably the sialysated oligosaccharides is
sialyllactose and/or disialo-lactoneotertaose (DS-LNT).
Glycosphingolipids are typically compounds with a monosaccharide
attached directly to a ceramide.
[0023] Preferably the NCC contains a ganglioside (a
glycosphingolipid). Gangliosides are typically highly complex
oligoglycosylceramides, which contain one or more sialic acid
groups (N-acyl, especially acetyl, derivatives of neuraminic acid,
abbreviated to "NANA") in addition to glucose, galactose and
galactosamine. For this application, especially buttermilk, egg
yolk lecithin are suitable raw material sources of gangliosides. (
Biochemistry, Donald Voet and Judith G. Voet, John Wiley and Sons,
Inc NY second edition chapter 23). Hence the present composition
preferably contains egg yolk lecithin and/or buttermilk.
[0024] In a particularly preferred embodiment the present
composition contains a ganglioside selected from the group
consisting GM3, GM1 and GD1.
[0025] In a further preferred embodiment, the present composition
contains sulfoglycosphingolipids as the NCC.
Sulfoglycosphingolipids are sulfate esters of galactosylceramide
and lactosylceramide (often referred as "sulfatides" or "lipid
sulfates"), with a sulfate group linked to position 3 of the
galactosyl moiety.
Acidic Oligosaccharides
[0026] The present composition preferably includes acidic
oligosaccharides with a DP from 2 to 100, preferably from 2 to 60.
The term acid or acidic oligosaccharide refers to oligosaccharides
comprising at least one acidic group selected from the group
consisting of N-acetylneuraminic acid, N-glycoloylneuraminic acid,
free or esterified carboxylic acid, sulfuric acid group and
phosphoric acid group. The acidic oligosaccharide preferably
comprises uronic acid units (i.e. uronic acid polymer), more
preferably galacturonic acid units. The present composition
preferably contains between 0.1 and 10 grams acid oligosaccharides
per 100 gram dry weight of the present composition, more preferably
between 1 and 6 grams per 100 gram dry weight.
##STR00001##
wherein:
[0027] R is preferably selected from the group consisting of
hydrogen, hydroxy or acid group, preferably hydroxy; and at least
one selected from the group consisting of R2, R3, R4 and R5
represents N-acetylneuraminic acid, N-glycoloylneuraminic acid,
free or esterified carboxylic acid, sulfuric acid group and
phosphoric acid group, and the remaining of R2, R3, R4 and R5
representing hydroxy and/or hydrogen. Preferably one selected from
the group consisting of R2, R3, R4 and R5 represents
N-acetylneuraminic acid, N-glycoloylneuraminic acid, free or
esterified carboxylic acid, sulfuric acid group or phosphoric acid
group, and the remaining represent hydroxy and/or hydrogen. Even
more preferably one selected from the group consisting of R2, R3,
R4 and R5 represents free or esterified carboxylic acid and the
remaining of R2, R3, R4 and R5 representing hydroxy and/or
hydrogen; and n is an integer and refers to a number of hexose
units (see also Degree of Polymerisation, below), which may be any
hexose unit. Suitably n is an integer between 1-5000. Preferably
the hexose unit(s) is a uronic acid unit.
[0028] Most preferably R1, R2 and R3 represent hydroxy, R4
represent hydrogen, R5 represents carboxylic acid, n is any number
between 1 and 250, preferably between 1 and 10 and the hexose unit
is galacturonic acid.
[0029] The detection, measurement and analyses of the preferred
acid oligosaccharides as used in the present method are given in
applicants earlier patent application relating to acid
oligosaccharides, i.e. WO 0/160378.
[0030] Preferably, the acid oligosaccharide has one, preferably
two, terminal uronic acid units, which may be free or esterified.
Preferably the terminal uronic acid unit is selected from the group
consisting of galacturonic acid, glucuronic acid, guluronic acid,
iduronic acid, mannuronic acid, riburonic acid and alturonic acid.
These units may be free or esterified. In an even more preferred
embodiment, the terminal hexose unit has a double bond, which is
preferably situated between the C4 and C5 position of the terminal
hexose unit. Preferably one of the terminal hexose units comprises
the double bond. The terminal hexose (e.g. uronic acid) preferably
has a structure according to FIG. 2.
wherein;
[0031] R is preferably selected from the group consisting of
hydrogen, hydroxy or acid group, preferably hydroxy (see above);
and at least one selected from the group consisting of R2, R3, R4
and R5 represents N-acetylneuraminic acid, N-glycoloylneuraminic
acid, free or esterified carboxylic acid, sulfuric acid group and
phosphoric acid group, and the remaining of R2, R3, R4 and R5
representing hydroxy and/or hydrogen. Preferably one selected from
the group consisting of R2, R3, R4 and R5 represents
N-acetylneuraminic acid, N-glycoloylneuraminic acid, free or
esterified carboxylic acid, sulfuric acid group and phosphoric acid
group, and the remaining of R2, R3, R4 and R5 represent hydroxy
and/or hydrogen. Even more preferably one selected from the group
consisting of R2, R3, R4 and R5 represents free or esterified
carboxylic acid and the remaining of R2, R3, R4 and R5 represent
hydroxy and/or hydrogen; and n is an integer and refers to a number
of hexose units (see also Degree of Polymerisation, below), which
may be any hexose unit. Suitably n is an integer between 1-100
representing the number of hexose units said hexose units
preferably being uronic acid, even more preferably being
galacturonic acid units. The carboxylic acid groups on these units
may be free or (partly) esterified, and are preferably at least
partly methylated.
[0032] Most preferably, R2 and R3 represent hydroxy, R4 represent
hydrogen and R5 represents free or esterified carboxylic acid.
[0033] The acid oligosaccharides used in the invention are
preferably prepared from pectin, pectate, alginate, chondroitine,
hyaluronic acids, heparine, heparane, bacterial carbohydrates,
sialoglycans, fucoidan, fucooligosaccharides or carrageenan, more
preferably from pectin and/or alginate. Preferably pectin, often
biochemically depolymerized is used. Most preferably pectin
depolymerized with pectin lyase is used.
Bivalent Cation
[0034] The present nutritional composition preferably contains a
bivalent cation. The bivalent cation enhances proximity of the
nucleotide component and the NCC, further modifying the charge
density and improving biological activity. Preferably the present
composition contains at least one bivalent cation selected from the
group consisting of magnesium, calcium, iron, chromium, manganese,
molybdenum, copper and zinc. Preferably the present composition
contains at least calcium and/or zinc.
[0035] Zinc is advantageously included in the present composition.
Zinc enhances the biological activity of the nucleotides when
combined with the present NCC, and also s an essential
micronutrient for growth and development of the immune function,
particularly for infants. Zinc deficiency impairs overall immune
function and resistance to infection. Hence, the present
composition advantageously comprises zinc, preferably in an amount
of 2 to 100 mg zinc per 100 gram dry weight of the present
composition, even more preferably between 3 and 25 mg zinc per 100
g dry weight of the present composition. The weight of zinc is
calculated as elementary zinc.
[0036] In a further preferred embodiment, the present composition
contains calcium for improved charge interaction. Calcium is also
essential in an infants diet, and hence advantageously included in
the present composition. Preferably the present composition
contains between 150 and 1000 mg calcium by weight total dry weight
of the composition.
Macronutrients
[0037] The present composition can be advantageously used as an
infant formula. The infant formula preferably administered to the
infant in liquid form. The term infant includes weaning infants,
and toddlers.
[0038] In a preferred embodiment the present invention relates to
an nutritional composition which provides the macronutrients of the
infant diet. Hence, the present composition preferably contains 30
to 60 en % lipid; 5 to 15 en % protein; and 25 to 65 en %
carbohydrate. Preferably, the present composition contains 43 to 53
en % lipid; 7 to 11 en % protein; and 43 to 53 en % carbohydrate
(en % is short for energy percentage and represents the relative
amount each constituent contributes to the total caloric value of
the preparation). The term "protein" or protein component in this
context is the cumulative of protein, polypeptides, peptides and
amino acids. The carbohydrate in the present composition is
preferably provided largely by lactose, i.e. preferably at least 75
wt. % of total digestible carbohydrate is provided by lactose,
preferably at least 90 wt. %.
Essential Fatty Acids Content
[0039] The present composition preferably contains at least 10 wt.
% linoleic acid (LA) based on total fatty acids, preferably between
11 and 20 wt. %, more preferably between 12 and 15 wt. %. The
present composition preferably contains at least 1 wt. % alpha
linolenic acid (ALA) based on total fatty acids, preferably between
1.5 and 4 wt. % ALA, even more preferably between 2 and 2.5 wt. %.
To reduce intestinal stress, the weight ratio LA/ALA is preferably
between 2 and 10, preferably between 5 and 7.5. The present
composition preferably includes between 0.05 and 5 wt %
gamma-linolenic acid (GLA) based on total fatty acids, preferably
between 0.1 and 1 wt. %. Preferably the present composition
contains between 0.05 and 5 wt % steraidonic acid (STA) preferably
more preferably between 0.1 and 1 wt. %.
Long Chain-polyunsaturated Fatty Acid Content
[0040] The present composition preferably comprises at least one
long chain-polyunsaturated fatty acid with 20 or 22 carbon atoms
(LCPUFA) in an amount exceeding 0.1 wt. % based on total fatty
acids, selected from the group consisting of docosahexaenoic acid
(DHA), arachidonic acid (AA) and eicosapentaenoic acid (EPA).
Preferably the composition contains DHA in an amount exceeding 0.1
wt. % based on total fatty acids; and AA in an amount exceeding 0.1
wt. % based on total fatty acids.
[0041] Preferably at least one LCPUFA of this group is included in
an amount between 0.15 and 1 wt. % based on total fatty acid
content of the composition. Preferably at least two of these
LCPUFA's are present in an amount of between 0.15 and 1 wt. % based
on total fatty acid content of the composition. Preferably the
composition contains AA and DHA, even more preferably AA, DHA and
EPA.
[0042] The AA content preferably does not exceed 5 wt. %, more
preferably does not exceed 1 wt. %, most preferably between 0.1 and
0.6 wt. % of the total fatty acids. In the present composition, EPA
and/or DHA are advantageously added to balance the action of AA,
e.g. reduce the potential pro-inflammatory action of AA
metabolites. Excess metabolites from AA may cause inflammation.
Hence, the present composition preferably comprises AA, EPA and/or
DHA, wherein the weight ratio AA/DHA preferably is above 0.25,
preferably above 0.5, even more preferably above 1. The ratio
AA/DHA is preferably below 25, preferably below 10. The weight
ratio AA/EPA is preferably between 1 and 100, more preferably
between 5 and 20. The weight ratio EPA/DHA is preferably 1 or
lower, more preferably below 0.5.
[0043] In a preferred embodiment, the content of LCPUFA does not
exceed 3 wt. % of the total fatty acids as it is desirable to mimic
human milk as closely as possible. For the same reason, the present
composition preferably contains less than 1 gram omega-3 LCPUFA per
100 gram fatty acids, more preferably between 0.1 and 0.75 gram per
100 gram fatty acids. The omega-6 LCPUFA content preferably does
not exceed 2 gram per 100 gram fatty acids and is preferably
between 0.1 and 0.75 gram per 100 gram fatty acids.
[0044] The LCPUFAs and the other fatty acids may be provided as
free fatty acids, in riglyceride form, in phospholipid form, or as
a mixture of one of more of the above. The present composition
advantageously comprises at least one of AA and HA in phospholipid
form, as these reduce the incidence of inflammatory disorders of
the intestine. The present composition preferably comprises between
0.1 and 5 mg AA from phospholipid per gram total fat and between
0.1 and 5 mg HA from phospholipid per gram total fat. Preferably
the AA and/or DHA are at east partly present in the form of
phosphatidylcholine (PC) and/or hosphatidylethanolamine (PE), e.g.
AA and/or DHA containing PE and/or PC.
Oligosaccharides
[0045] The present composition preferably comprises indigestible
oligosaccharides with a degree of polymerisation (DP) of between 2
and 100. The oligosaccharides are believed to be important for
providing a suitable intestinal environment for improved
presentation and charge density of the combination of nucleotide
component and NCC. The indigestible oligosaccharides reduce the pH
of the intestinal environment, improving biological activity of the
nucleotides. Preferably, the present composition contains 0.1 to 12
grams indigestible oligosaccharides per 100 gram dry weight of the
composition, preferably between 3 and 8 grams, more preferably
between 5 and 7.5 grams. After reconstitution of the powder in
liquid and administration of the liquid formula to the infant,
these amounts of indigestible oligosaccharides provide the desired
effects without causing intestinal discomfort. Suitable
indigestible oligosaccharides are not or only partially digested in
the intestine by the action of acids or digestive enzymes present
in the human upper digestive tract (small intestine and stomach),
but are fermentable by the human intestinal flora. The
oligosaccharides are preferably water-soluble (exceeding a
solubility of 1 gram oligosaccharide per liter water). The average
DP of the present oligosaccharide is preferably below 40, even more
preferably below 20. Optimally, the present composition comprises
between 2 and 12 grams oligosaccharides with a DP of 2 to 60, more
preferably with a DP of 2 to 10 (i.e. the sum of the weights of
those oligosaccharides with a DP of 2, 3, 4, 5, 6, 7, 8, 9 and
10).
[0046] According to a further embodiment at least one of the
oligosaccharides of the present composition is selected from the
group consisting of inulin, fructooligosaccharides, indigestible
dextrins, galactooligosaccharides (including
transgalactooligosaccharides), xylooligosaccharides,
arabinooligosaccharides, glucooligosaccharides,
mannooligo-saccharides, lacto-N-neotetraose, fucooligosaccharides
(containing at least one fucose saccharide unit), acidic
oligosaccharides (e.g. uronic acid oligosaccharides such as pectin
oligosaccharides) and mixtures thereof.
[0047] Preferably, the present composition comprises at least one
selected from the group consisting of inulins and
fructooligosaccharides and at least one selected from the group
consisting of galactooligosaccharides (including
transgalactooligosaccharides) and pectin hydrolysate. In a
particularly preferred embodiment, the present composition
comprises 2 to 12 grams oligosaccharides with a DP of 2 to 10 and
.beta.-linked galactose and glucose saccharides, more preferably
transgalactooligosaccharides (i.e. [gal].sub.n-glu, wherein n is 2
to 10). In a particularly preferred embodiment, the present
composition comprises transgalactooligosaccharides (i.e.
[gal].sub.n-glu, wherein n is 2 to 10), pectin hydrolysate and at
least one selected from the group consisting of
fructooligosaccharides and inulin. The present oligosaccharide is
preferably derived from animal milk, a mixture of oligosaccharides
derived from animal milk or a fucosylated oligosaccharide
(oligosaccharide containing at least one fucose saccharide
unit).
[0048] For further improvement of gut maturation over the whole
area of the colon, preferably at least 10 wt. % of the
oligosaccharides in the present composition has a DP of 2 to 5
(i.e. 2, 3, 4 and/or 5) and at least 5 wt. % has a DP of 10 to 100.
Preferably at least 50 wt. %, more preferably at least 75 wt. % of
the oligosaccharides have a DP of 2 to 10 (i.e. 2, 3, 4, 5, 6, 7,
8, 9 and/or 10), because these are believed to work throughout the
ileum and proximal and middle parts of the colon and because the
weight percentage of oligosaccharides that needs to be incorporated
in the composition to achieve the desired effect is reduced.
Preferably, the Weight Ratios:
[0049] (oligosaccharides with DP 2 to 5): (oligosaccharides with DP
6 to 9); and
[0050] (oligosaccharides with DP 10 to 100): (oligosaccharides with
DP 6 to 9) are both above 1. Preferably both weight ratios are
above 2, even more preferably above 5.
[0051] The present composition preferably comprises 0.5 to 10 gram
galactooligosaccharide with DP between 2 and 10 per 100 gram dry
weight of the composition, more preferably between 1 and 5 gram.
The preferred galactooligosaccharides is
transgalactooligosaccharide, as this best mimics human milk
oligosaccharides. The present invention preferably comprises 0.5 to
10 gram fructopolysaccharide with DP between 10 and 60 per 100 gram
dry weight of the composition, more preferably between 1 and 5
gram. The term "fructopolysaccharide" refers to a polysaccharide
carbohydrate comprising a chain of at least 10 .beta.-linked
fructose units.
Liquid
[0052] The present nutritional composition is preferably in powder
or liquid form or in tablet form, wherein said tablet has a weight
between 5 and 25 grams. Preferably, the present composition is
provided in powered form as this increases shelf life. The present
composition is preferably administered orally in liquid form. Prior
to the administration of the present composition, it is preferably
admixed with a liquid, preferably water.
[0053] Stool irregularities (e.g. hard stools, insufficient stool
volume, diarrhea) is a major problem in many babies and ill
subjects that receive liquid foods. It was found that stool
problems may be reduced by administering the present composition in
liquid form, having an osmolality between 50 and 500 mOsm/kg, more
preferably between 100 and 400 mOsm/kg, most preferably between 220
and 300 mOsm/kg.
[0054] In view of the above diarrhea problem, it is also important
that the liquid food does not have an excessive caloric density as
this causes significant intestinal stress. However, the formula
needs to provide sufficient calories to feed the infant. Hence, the
liquid food preferably has a caloric density between 0.5 and 0.9
kcal/ml, preferably between 0.6 and 0.8 kcal/ml.
Application
[0055] The present composition is advantageously administered to
infants with the age between 0 and 2 years. The present composition
can also be advantageously used in a method for providing the
nutritional requirements of a premature infant (an infant born
before 37 weeks gestation). In a preferred embodiment, the present
invention provides a method for feeding infants with an age between
0 and 30 day.
[0056] The present composition can be advantageously used to treat
or prevent diseases wherein a comprised immune system and/or
intestinal barrier immaturity is underlying the development of the
course of the disease. The present composition can thus be
advantageously used to treat or prevent diarrhea or allergy,
particularly in infants with an age between 0 and 2. The present
composition is particularly suitable for the treatment and/or
prevention of allergic rhinitis, allergic conjunctivitis, allergic
dermatitis, atopic dermatitis and/or food allergy. In a preferred
embodiment, the present method provides for a method for the
treatment and/or prevention of infections, said method comprising
administering the present composition.
[0057] The invention is further illustrated by means of the
following examples:
EXAMPLE 1
Infant nutrition
[0058] A liquid infant nutrition, prepared by admixing 13.9 g
powder with water to yield 100 ml final product, said liquid
product comprising per 100 ml:
TABLE-US-00001 Energy: 66 kcal Protein: 8 en % 1.3 g (containing
0.6 g casein; 0.8 g whey; 0.072 g L-arginine) Digestible 44 en %
carbohydrates: 7.4 g (containing 7.3 g lactose) Fat: 48 en % 3.5 g
(containing 0.41 g linoleic acid; 0.08 g .alpha.-linolenic acid;
0.012 g arachidonic acid; 0.002 g eicosapentanoic acid; 0.006 g
docosahexaenoic acid; 1.4 g oleic acid;) Fibre: 0.8 g (containing
0.05 g fructopolysaccharide (Raftiline HP .TM., Orafti, Tienen,
Belgium); 0.55 g transgalactooligosaccharides (Vivinal-GOS .TM.
(Borculo Domo Ingredients, Netherlands); 0.20 g pectin hydrolysate
prepared as described in EP1373543, example 1. Nucleotide
components: 0.89 mg Cytidine-5-monophosphate; 0.55 mg
Uridine-5-monophosphate; 0.82 mg Adenosine-5-monophosphate; 0.20 mg
Guanosine-5-monophosphate; 0.34 mg Inosine-5monophosphate. NCC: 5
mg GM3, 50 mg pectin derived oligosaccharides with DP between 5 and
50, and 20 mg sialyllactose Calcium: 53 mg calcium Zinc: 0.8 mg
zinc Osmolarity: 300 mOsmol/l
[0059] The composition further contains choline (6 mg/100 ml) and
taurine (6.3 mg/100 ml); minerals and trace elements and vitamins
in amounts in compliance with the international guidelines for
infant milk formula.
EXAMPLE 2
[0060] Composition according to example 1, wherein the nucleotide
component is replaced by dinucleosidpolyphosphates (NpxN) Gp4G
EXAMPLE 3
[0061] Composition according to example 1, wherein the nucleotide
component is an DNA/RNA oligomers extract
EXAMPLE 4
[0062] Composition according to example 1, comprising 1 wt. %
D-ribose based on total dry weight of the composition.
* * * * *