CN108697141A - Nutrient formulation object containing indigestible oligosaccharides and non-replicating lactic acid producing bacteria - Google Patents

Nutrient formulation object containing indigestible oligosaccharides and non-replicating lactic acid producing bacteria Download PDF

Info

Publication number
CN108697141A
CN108697141A CN201680082809.0A CN201680082809A CN108697141A CN 108697141 A CN108697141 A CN 108697141A CN 201680082809 A CN201680082809 A CN 201680082809A CN 108697141 A CN108697141 A CN 108697141A
Authority
CN
China
Prior art keywords
alimentation composition
alimentation
oligosaccharides
lactic acid
streptococcus thermophilus
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
CN201680082809.0A
Other languages
Chinese (zh)
Inventor
J·科诺尔
H·鲍里迪尤斯
A·R·奥泽尔
A·J·纳奥塔
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Nutricia NV
Original Assignee
Nutricia NV
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Nutricia NV filed Critical Nutricia NV
Publication of CN108697141A publication Critical patent/CN108697141A/en
Pending legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/20—Reducing nutritive value; Dietetic products with reduced nutritive value
    • A23L33/21—Addition of substantially indigestible substances, e.g. dietary fibres
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/135—Bacteria or derivatives thereof, e.g. probiotics
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/40—Complete food formulations for specific consumer groups or specific purposes, e.g. infant formula
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/702—Oligosaccharides, i.e. having three to five saccharide radicals attached to each other by glycosidic linkages
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/66—Microorganisms or materials therefrom
    • A61K35/74—Bacteria
    • A61K35/741—Probiotics
    • A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/66—Microorganisms or materials therefrom
    • A61K35/74—Bacteria
    • A61K35/741—Probiotics
    • A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
    • A61K35/745—Bifidobacteria
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/04—Immunostimulants

Abstract

A kind of secretory IgA comprising indigestible oligosaccharides and non-replicating bifidobacterium breve and/or the alimentation composition of streptococcus thermophilus collaboration stimulation baby.

Description

Nutrient formulation object containing indigestible oligosaccharides and non-replicating lactic acid producing bacteria
Technical field
The present invention relates to the infant nutrient fields for improving mucosal immune system.
Background technology
It has been recognized that the best nutritional of ewborn infant is human milk.When mother can not its baby of breast-feeding or selection not It is considered as best substitute based on the infant formula (IF) that ripe human milk forms when carrying out breast-feeding.Improve baby The matter quantifier elimination of formulation is not necessarily the accurate composition for human milk simulating, but exceeds in breast-feeding to realize The functional effect in terms of nutrition is only observed in baby.
Human milk is rich in secretory IgA (sIgA), as the first line of defence to protect the gut barrier of baby from enteron aisle The infringement of toxin and pathogenic microorganism.SIgA is resistant to digestive ferment, and by blocking antigen and pathogenic microorganism to enter They are trapped in mucus and promote their removal by the activity of wriggling and mucociliary by epithelial receptor, from And them is promoted to be removed from enteron aisle.In addition, sIgA plays a role in mucosa-immune system of defense and enteral stable state, will not swash It sends out and even improves inflammatory reaction.In contrast, the standard infant formula object based on milk elements has much lower sIgA dense Degree, and compared with breast-fed babies, have the sIgA reduced horizontal with standard infant formula object fed infant.
EP 2 318 046 discloses the combination of probiotics and secretory IgA for treating or preventing inflammation.EP 2 315 595 disclose the purposes of the immunoglobulin secretion of probiotics living for increasing caesarean birth (C section) baby.Birth When, the baby by caesarean deliveries is sterile, and in the case of no micropopulation, and IgA secretions are serious to be reduced, because This needs to take in probiotics living.Fukushima et al. (1998, Int J Food Micribiol 42:39-44) have studied Influence of probiotic bifidobacteria (Bifidobacterium lactis) bacterial strain to the IgA secretions of the larger children of a group, and It was found that the horizontal of the total IgA and IgA of poliomyelitis virus increases.Probiotics is lactic acid producing bacteria living, such as breast living The Bifidobacterium of acidfast bacilli or work.
Indigestible oligosaccharides influence enteron aisle sIgA responses also by them to the influence that micropopulation forms. Scholtens et al. (2008, J Nutr 138:1141-1147) and Bakker-Zierikzee et al. (2006, Pediatr Allergy Immunol 17:134-140) find that feeding is supplemented with the excrement of the healthy babies of the formulation of scGOS/lcFOS SIgA levels are horizontal higher than the excrement sIgA of the baby of feeding standard recipe object, to support this hypothesis.
Mulli é et al. (2004, Ped Res 56:It 791-795) discloses in the newborn of health, fermentating formula object Consumption with give generate after vaccine have the specific increase of enteron aisle sIgA antibody related poliovirus, but Total IgA titres are not influenced.
WO 2009/151330 disclose it is a kind of for surgical neonate by lactic acid producing bacteria and indigestible oligosaccharides Fermentation and the composition that obtains.Purpose is inducing tolerance, to contribute to subsequent work bacteria planting.It does not disclose pair The influence of IgA secretions.WO 2009/151331 discloses a kind of immunostimulatory compositions, it includes indigestible oligosaccharides and with The product that Bifidobacterium obtains after incubating.By stimulating the Th1 responses of systemic immune system and reducing the Th2 of systemic immune system Response, reaction of inoculation increase and allergy are reduced.WO 2009/151329 discloses a kind of composition, and it includes indigestible widows Sugar and the product obtained by being incubated with Bifidobacterium, for reducing bacterial translocation and improving gut barrier function.Its purpose It is to prevent general infection in this way.It includes inactive bifidobacterium breve that WO 2008/153377, which is disclosed a kind of, The infant formula of (Bifidobacterium breve) and indigestible oligosaccharides.This document is not mentioned anti-to mucosa-immune The influence of imperial and IgA secretions.US 2014/193542 is related to providing based on free amino acid and containing prebiotics and probiotics Infant nutritional compositions without anaphylactogen.Although it is horizontal to have monitored IgE and IgG, this document does not mention secretory IgA.WO 2014/201037 disclose probiotics, prebiotics, symphysis unit and antibiotic for treat and antibiosis extract for treating and various immunological diseases The purposes of the relevant mammal micropopulation variation of disease.It is prebiotic in the case of open prebiotics and the conjugate of probiotics Member is considered stimulating growth or the metabolic activity of probiotics.
Invention content
In the clinical test of health full term baby, finds to work as and give without indigestible oligosaccharides and be free of non-replicating The control formula object of lactic acid producing bacteria, comprising the non-replicating lactic acid producing bacteria selected from bifidobacterium breve and streptococcus thermophilus but not Infant formula containing indigestible oligosaccharides or the formulation comprising indigestible oligosaccharides but without non-replicating lactic acid producing bacteria Compared to when, observe and give comprising at least one non-replicating lactic acid producing bacteria bacterium selected from bifidobacterium breve and streptococcus thermophilus Strain and include indigestible oligosaccharides infant formula make intestinal secretion type IgA (sIgA) increase significantly.The secretion collaboration of IgA increases Adduction and more like with the sIgA in the reference group of breast-feeding.This further demonstrates that the collaboration of mucosa-immune system of defense increases By force.
Unexpectedly, synergistic effect cannot be construed to the direct phase interaction between indigestible oligosaccharides and lactic acid producing bacteria With reason is that bacterium is inactivated;It can not be construed to increased enteric microorganism activity, reason is not bright with intestinal pH Aobvious correlation.
Specific implementation mode
Therefore, the present invention relates to a kind of methods of the IgA secretions of human experimenter increasing by 0 to 36 monthly age comprising gives Give human experimenter include at least one non-replicating lactic acid producing bacteria bacterial strain selected from bifidobacterium breve and streptococcus thermophilus and Include the alimentation composition of indigestible oligosaccharides, the composition has 2.5 to 15 weight of dry weight meter based on alimentation composition Measure the indigestible oligosaccharides of %.
In one embodiment, the method for the IgA secretions of the human experimenter for increasing by 0 to 36 monthly age of the invention It is non-therapeutic method.
The present invention can also be expressed as at least one thin selected from the non-replicating lactic acid producing of bifidobacterium breve and streptococcus thermophilus The alimentation composition that bacteria strain and indigestible oligosaccharides are secreted in the IgA for preparing the human experimenter for increasing by 0 to 36 monthly age In purposes, wherein the alimentation composition include 2.5 to the 15 weight % of dry weight meter based on alimentation composition it is indigestible Oligosaccharides.
The present invention can also be expressed as a kind of including at least one non-replicating selected from bifidobacterium breve and streptococcus thermophilus The alimentation composition of lactic acid producing bacteria bacterial strain and indigestible oligosaccharides, wherein the alimentation composition includes to be based on alimentation composition 2.5 to 15 weight % of dry weight meter indigestible oligosaccharides, be used for increase by 0 to 36 monthly age human experimenter IgA secretion.
On the other hand, the present invention relates to it is a kind of improve 0 to 36 monthly age human experimenter mucosa-immune defence method, It includes that give human experimenter include that at least one non-replicating lactic acid producing selected from bifidobacterium breve and streptococcus thermophilus is thin Bacteria strain and include indigestible oligosaccharides alimentation composition, the composition have the dry weight meter 2.5 based on alimentation composition To the indigestible oligosaccharides of 15 weight %.
In one embodiment, the mucosa-immune defence of the human experimenter for improving for 0 to 36 monthly age of the invention Method be non-therapeutic method.
The present invention can also be expressed as at least one thin selected from the non-replicating lactic acid producing of bifidobacterium breve and streptococcus thermophilus The nutrition group that bacteria strain and indigestible oligosaccharides are defendd in the mucosa-immune for preparing the human experimenter for improving for 0 to 36 monthly age Close object in purposes, wherein the alimentation composition include 2.5 to the 15 weight % of dry weight meter based on alimentation composition can not Digest oligosaccharides.
The present invention can also be expressed as a kind of including at least one non-replicating selected from bifidobacterium breve and streptococcus thermophilus The alimentation composition of lactic acid producing bacteria bacterial strain and indigestible oligosaccharides, wherein the alimentation composition includes to be based on alimentation composition 2.5 to 15 weight % of dry weight meter indigestible oligosaccharides, be used for improve 0 to 36 monthly age human experimenter mucosa-immune Defence.
Lactic acid producing bacteria
The method of the present invention or with alimentation composition on the way --- hereinafter also referred to alimentation composition of the invention --- Including the lactic acid producing bacteria selected from bifidobacterium breve and streptococcus thermophilus.
Preferably, composition includes streptococcus thermophilus (S.thermophilus) bacterial strain.Preferably, streptococcus thermophilus is the bottom of at Betagalactosidase activity is played in object fermentation process.The selection of suitable strains of streptococcus thermophilus is recorded in EP's 778885 In embodiment 2 and the embodiment of FR 2,723,960 1.Alimentation composition includes to be less than 106Cfu streptococcus thermophilus bacteriums/g dry weights, Preferably alimentation composition includes to be less than 105Cfu streptococcus thermophilus/g dry weights, even more preferably less than 103Cfu streptococcus thermophilus/ G dry weights.In one embodiment, alimentation composition includes 0-104Cfu streptococcus thermophilus/g dry weights, preferably 0-103Cfu/g groups Close the dry weight of object.
The amount for the non-replicating streptococcus thermophilus that alimentation composition includes is at least 107Cfu streptococcus thermophilus bacteriums/g is dry Weight, preferably greater than 108Cfu/g dry weights, even more preferably greater than 109Cfu/g dry weights.Preferably, alimentation composition includes and is less than 1014Cfu non-replicatings streptococcus thermophilus/g dry weights, even more preferably less than 1012The dry weight of cfu/g alimentation compositions.
For the present invention preferred strains of streptococcus thermophilus by Compagnie Gervais Danone be deposited in by Institut Pasteur, 25rue du Docteur Roux, the Collection Nationale that Paris, France are managed At de Cultures de Microorganismes (CNCM), in the preservation on the 23rd of nineteen ninety-five August registration number be I-1620 and In the preservation on the 25th of August in 1994 registration number be I-1470.
Preferably, composition includes bifidobacterium breve strain.Preferred bifidobacterium breve strain is fed from the human milk of health Those of isolated in the excrement of foster baby.Normally, can be commercially available from the lactic acid bacteria producer, but its also can directly from It detaches, identify, characterize in excrement and produce.According to a preferred embodiment, composition of the invention contains at least one Bifidobacterium breve selected from the following:Bifidobacterium breve Bb-03 (Rhodia/Danisco), bifidobacterium breve M-16V (Morinaga), bifidobacterium breve R0070 (Institute Rosell, Lallemand), bifidobacterium breve BR03 (Probiotical), bifidobacterium breve BR92 (Cell Biotech) DSM 20091, LMG 11613 and it is deposited in Paris, FRA Bifidobacterium breve I-2219 at CNCM.Most preferably, inactive bifidobacterium breve is inactive bifidobacterium breve M-16V (Morinaga) or bifidobacterium breve I-2219, even more preferably bifidobacterium breve I-2219.
Alimentation composition includes to be less than 106Cfu bifidobacterium breves bacterium/g dry weights, preferably alimentation composition include to be less than 105Cfu bifidobacterium breves/g dry weights, even more preferably less than 103Cfu bifidobacterium breves/g dry weights.In one embodiment, Alimentation composition includes 0-104Cfu bifidobacterium breves/g dry weights, preferably 0-103Cfu bifidobacterium breves/g alimentation compositions are done Weight.
The amount for the non-replicating bifidobacterium breve that alimentation composition includes is at least 107Cfu/g dry weights, preferably greater than 108Cfu/g dry weights, even more preferably greater than 109Cfu/g dry weights.Preferably, alimentation composition includes to be less than 1013Cfu not replicated Type bifidobacterium breve/g dry weights, even more preferably less than 1011The dry weight of cfu/g alimentation compositions.
Preferably, alimentation composition of the invention includes to be less than 10 in total6The streptococcus thermophilus and bifidobacterium breve/g of cfu Dry weight, preferably alimentation composition include to be less than 10 in total5Streptococcus thermophilus and bifidobacterium breve/g dry weights of cfu, even more Preferably smaller than 103The dry weight of cfu/g alimentation compositions.In one embodiment, alimentation composition includes 0-10 in total4Cfu's Streptococcus thermophilus and bifidobacterium breve/g dry weights, preferably 0-103The dry weight of cfu/g alimentation compositions.
The equivalent of cfu can be suitably by with the bifidobacterium breve probe and primer pair as disclosed in WO 2005/039319 Including the composition (such as infant formula) of inactive bifidobacterium breve carries out 5'Nuclease assay measures, and by its with by Comparable product obtains (such as the standard infant formula object of the active bifidobacterium breve cfu for the drying that known quantity has wherein been added) Calibration curve be compared.Dry active Bifidobacterium can be commercially available as described above.
Most preferably, alimentation composition includes by the lactobacillus-fermented comprising both bifidobacterium breve and streptococcus thermophilus Fermented ingredient.In one embodiment, lactobacillus-fermented is fermented by streptococcus thermophilus and bifidobacterium breve.In a reality It applies in scheme, alimentation composition includes fermented ingredient, and wherein lactic acid bacteria is inactivated after fermentation.
Bacterium of the alimentation composition of the present invention comprising non-replicating lactic acid producing bacteria and/or from lactic acid producing bacteria is broken Piece, wherein lactic acid producing bacteria are selected from bifidobacterium breve and streptococcus thermophilus, and by being more than 107Cfu/g, more preferable 108cfu/g, Even more preferably 109Cfu/g or its equivalent obtain, the dry weight meter based on final composition.Preferably, non-replicating lactic acid producing is thin Bacterium and/or bacterial debris from lactic acid producing bacteria --- wherein lactic acid producing bacteria is selected from bifidobacterium breve and thermophilus Bacterium --- by being less than 1 × 1014Cfu/g, more preferable 1 × 1013Cfu/g, even more preferably 1 × 1012Cfu/g or its equivalent obtain, Dry weight meter based on final composition.
Preferably, alimentation composition of the invention is not by lactobacillus bulgaricus (Lactobacillus bulgaricus) Fermentation.The product of bulgaria lactobacillus fermentation is considered being not suitable for baby, this is because in small baby, by D-lactate It is converted into dehydrogenase of the activity far below conversion Pfansteihl salt of the specific dehydrogenase of acetonate.
The ablation method of bifidobacterium breve and/or streptococcus thermophilus
The living cells of lactic acid producing bacteria bifidobacterium breve and/or streptococcus thermophilus in alimentation composition is preferred after fermentation It is substantially all to become non-replicating.Streptococcus thermophilus and/or bifidobacterium breve cell can be by methods known in the art systems At inactive, including heat treatment step (including sterilization, pasteurization, UHT processing), radiation (UV), with oxygen treatments applied, with killing Bacteriocin for example alcohol treatment, ultrasound, apply hyperpressure, high pressure homogenizing and use cell disruptor, preferably by heat at Reason.
Preferably, streptococcus thermophilus and/or bifidobacterium breve are heat-treated after fermentation step.Make streptococcus thermophilus And/or it is (flash distillation) pasteurization, sterilization, superhigh temperature processing, high temperature/short that bifidobacterium breve, which becomes the preferred method of non-replicating, When be heat-treated and/or be spray-dried at the nonviable temperature of lactic acid producing bacteria.Cell fragment is preferably obtained by being heat-treated.
Pass through the heat treatment, preferably at least 95%, more preferably at least 97.5%, even more desirably at least 99% short bifid Bacillus and/or streptococcus thermophilus become non-replicating.Heat treatment preferably at a temperature of 70 to 180 DEG C, preferably 80 to 150 DEG C into Row preferably from about 3 minutes to 2 hours, preferably carries out 5 minutes to 40 minutes at a temperature of 80-140 DEG C.
The inactivation of lactic acid producing bacteria advantageously causes less rear acidification and safer product.It is given when by alimentation composition When giving baby or child, this is particularly advantageous.Suitably after fermentation, composition can be carried out pasteurization or sterilization and Such as be spray-dried or be lyophilized, it is a kind of suitable in the form of being prepared in the final product to provide.
Non-replicating lactic acid bacteria will not form bacterium colony by conventional electro-plating method.The conventional electro-plating method is summarized in In microbiology books:James Monroe Jay,Martin J.Loessner,David A.Golden.2005.Modern Food microbiology. the 7th edition, Springer Science, New York, N.Y. page 790.Normally, science is thin Born of the same parents lack expressible as follows:It is being inoculated with the bacteria preparation (" non-replicating " sample) of various concentration and is incubating under suitable condition (aerobic and/or oxygen-free atmosphere;Temperature appropriate and growth medium and incubative time appropriate, at least 24 hours) after, There is no there is no increased turbidity in visible bacterium colony or liquid growth media on agar plate.
Non-replicating bacterium is also referred to as nonactive bacterium, not educable bacterium or non-growing bacterium sometimes.It is non-multiple Type bacterium processed includes metabolic active cells, killed cells or dead cell or bacterial cellular debris.
Fermented ingredient
The alimentation composition of the present invention preferably comprises fermented ingredient.Preferably, fermented ingredient is by lactic acid producing bacteria, preferably Streptococcus thermophilus and/or the component of bifidobacterium breve fermentation.It is preferred that fermenting in the preparation process of alimentation composition.It is preferred that Ground, fermented ingredient are newborn derived products, are the newborn substrate to be fermented by lactic acid producing bacteria, and the newborn substrate includes at least one Kind newborn substrate selected from the following:Breast, whey, lactalbumin, lactalbumin hydrolysate, casein, casein hydrolysate and lactose, Or mixtures thereof.Suitably, including the alimentation composition and preparation method thereof of fermented ingredient and indigestible oligosaccharides is recorded in WO 2009/151330, in WO 2009/151331 and WO 2013/187764.
Fermented ingredient preferably comprises bacterial cellular debris, such as glycoprotein, glycolipid, peptide glycan, lipoteichoicacid (LTA), fat egg In vain, nucleotide and/or capsular polysaccharide.Advantageously the fermented ingredient comprising inactivation of bacterial and/or cell fragment is directly used as A part for final nutrition product, because this will lead to the bacterial cellular debris of higher concentration.When using commercial formulation, usually These preparations are washed, and material is detached with the aqueous growth medium comprising bacterial cellular debris, it is thin to reduce or eliminate The presence of bacterium cell fragment.In addition, in the fermentation and/or other interactions of lactic acid producing bacteria and newborn substrate, formed in addition Bioactive compound, such as biologically active peptide and/or oligosaccharides equally stimulate mucosa-immune system of defense.Therefore, with it is non- The newborn derived product of fermentation is compared, and the newborn derived product of fermented ingredient, particularly fermentation is considered to have improved effect.
Preferably, alimentation composition includes based on 5 to 97.5 weight % of dry weight meter, more preferable 10 to 95 weight %, more excellent Select the fermented ingredient of 20 to 90 weight %, even more preferably 25 to 60 weight %.As the mode for indicating attenuation degree, can adopt With the total level of lactic acid in alimentation composition and lactate, produced because this is that the metabolism that lactic acid producing bacteria is generated in fermentation is whole Object.The present invention alimentation composition include the dry weight meter based on composition in total 0.02 to 1.5 weight %, more preferable 0.05 to The lactic acid and lactate of 1.0 weight %, even more preferably 0.05 to 0.5 weight %.Preferably, at least 50 weight %, very in total To the more preferably at least lactic acid of 90 weight % and lactate in the form of L (+)-isomers.Therefore, in one embodiment, L The summation of (+)-lactic acid and L (+)-lactate is more than 50 weight %, more preferably greater than 90 weight %, based on lactic acid and lactate Summation meter.Herein, L (+)-lactate and L (+)-lactic acid are also referred to as Pfansteihl salt and Pfansteihl.
Fermentation process
Newborn substrate to be fermented is suitble to be present in aqueous culture medium.Newborn substrate to be fermented is preferably selected from breast, whey, breast Albumin, lactalbumin hydrolysate, casein, casein hydrolysate and lactose and its mixture.Breast can be rich milk, half degreasing Breast and/or skimmed milk.Preferably, newborn substrate to be fermented includes skimmed milk.Whey can be sweet whey and/or acid whey.It is preferred that Ground, the concentration that whey contains the aqueous culture medium of newborn substrate with 3 to 80g dry weights/L exist, and more preferable 40 to 60g/L.Preferably, Lactalbumin hydrolysate exists with 2 to 80g dry weights/L aqueous culture mediums for containing newborn substrate, and more preferable 5 to 15g/L.Preferably, Lactose exists with the aqueous substrates of 5 to 50g dry weights/L, and more preferable 1 to 30g/L.Preferably, contain the aqueous culture medium packet of newborn substrate Containing buffer salt, pH is kept within the required range.It is preferable to use sodium dihydrogen phosphates or potassium dihydrogen phosphate as buffer salt, preferably It is used with 0.5 to 5g/L, more preferable 1.5 to 3g/L.Preferably, the aqueous culture medium for containing newborn substrate includes cysteine, It is 0.1 to 0.5g/L aqueous substrate to measure, more preferable 0.2 to 0.4g/L.The presence of cysteine causes substrate to have low oxidation Reduction potential, this is conducive to the activity of lactic acid producing bacteria, particularly Bifidobacterium.Preferably, contain the aqueous culture of newborn substrate Base is comprising yeast extract, the aqueous culture medium for containing newborn substrate in an amount of from 0.5 to 5g/L, and more preferable 1.5 to 3g/L.Yeast carries It is the enzyme cofactor of lactic acid producing bacteria and the abundant source of growth factor to take object.It is thin that the presence of yeast extract will enhance lactic acid producing The fermentation of bacterium.
Suitably, before fermentation step to newborn substrate, particularly the aqueous culture medium containing newborn substrate carry out Pasteur go out Bacterium, to eliminate the presence of unwanted bacterium living.Suitably, pasteurization is carried out to product after fermentation, so that enzyme inactivates.It closes Suitable ground, enzyme inactivation carry out 3 minutes at 75 DEG C.Suitably, the aqueous culture medium containing newborn substrate homogenize before fermentation and/or Newborn derived product homogenizes after fermentation.Homogenizing leads to more stable substrate and/or tunning, especially depositing in fat Under.
Inoculum density is preferably 1 × 102To 5 × 1010, preferably 1 × 104To 5 × 109Cfu streptococcus thermophilus and/or short double Discrimination bacillus/ml contains the aqueous culture medium of newborn substrate, and more preferably 1 × 107To 1 × 109Cfu/ml contains the aqueous training of newborn substrate Support base.Final bacterial density after fermentation is preferably 1 × 103To 1 × 1010, more preferable 1 × 104To 1 × 109Cfu/ml contains breast The aqueous culture medium of substrate.
Fermentation is preferably in about 20 DEG C to 50 DEG C, 30 DEG C to 45 DEG C more preferable, even more preferably about 37 DEG C to 42 DEG C of temperature Lower progress.The growth of streptococcus thermophilus and/or bifidobacterium breve and/or active optimum temperature.
Incubation is preferably carried out at 4 to 8, more preferable 6 to 7.5 pH.The pH will not cause protein precipitation and/or not Good taste, while lactic acid producing bacteria such as bifidobacterium breve and/or streptococcus thermophilus can make newborn fermenting substrate.
Incubative time is preferably 10 minutes to 48 hours, preferably 2 hours to 24 hours, more preferable 4 hours to 12 hours.Foot Enough the long time makes it possible to largely be fermented and generated simultaneously immunogenicity cell fragment such as glycoprotein, sugar Fat, peptide glycan, lipoteichoicacid (LTA), flagellum, lipoprotein, DNA and/or capsular polysaccharide, however for economic reasons, when incubation Between do not need it is too long.
Preferably, newborn substrate, preferably skimmed milk are subjected to pasteurization, it is cooling, and utilize one or more streptococcus (Streptococcus) strain fermentation is to a degree of acidity, cooling and fermentation product and is stored under the acidity.It is preferred that Ground uses one or more bifidobacterium species for fermentation to prepare the second newborn derived product as replacement in a similar manner. Then, preferably by two kinds of tunnings mix and with constitute infant formula the other components in addition to fatty ingredient Mixing.Preferably, mixture is preheated, then fat is added in (in-line) in the production line, homogenizes, pasteurization is simultaneously done It is dry.
The method for preparing suitable fermented ingredient is known per se.EP 778885 --- it is included in by reference Herein --- a kind of appropriate method preparing fermentation component is specifically disclosed in embodiment 7.FR 2723960 --- by drawing Mode is included in herein --- a kind of appropriate method preparing fermentation component is specifically disclosed in embodiment 6.In brief, Lactose and optional other macronutrients (such as fat (preferred plant fat), casein, lactalbumin, vitamins will be included And/or minerals etc.) newborn derivative products, preferably pasteurization the derivative substrate of breast be concentrated into such as 15 to 50% dry Then matter is inoculated with streptococcus thermophilus, such as with containing 106To 10105% culture of a bacterium/ml is inoculated with.Preferably, institute It includes milk peptide to state newborn derivative products.The temperature of fermentation and duration are as described above.It suitably, after fermentation, can be right Including the composition of fermentation protein carries out pasteurization or sterilization and is for example spray-dried or is lyophilized, to provide a kind of be suitable for The form prepared in final products..
The preferred method for preparing tunning is disclosed in WO 01/01785, is more specifically disclosed in Examples 1 and 2. The preferred method for preparing tunning is recorded in WO 2004/093899, is more specifically recorded in embodiment 1.
Indigestible oligosaccharides
The composition of the present invention includes indigestible oligosaccharides, and preferably comprises at least two kinds of indigestible oligosaccharides, especially It is the indigestible oligosaccharides of two kinds of separate sources.The secretion of the presence stimulation sIgA of indigestible oligosaccharides.Indigestible oligosaccharides In the presence of stimulation mucosa-immune system of defense.Therefore, indigestible oligosaccharides are existed simultaneously and are selected from bifidobacterium breve and/or thermophilic chain The non-replicating lactic acid producing bacteria of coccus synergistically acts on and advantageously causes higher IgA secretions in enteron aisle.Therefore, it deposits simultaneously Synergistically act in indigestible oligosaccharides and non-replicating lactic acid producing bacteria selected from bifidobacterium breve and/or streptococcus thermophilus and Advantageously cause increased mucosa-immune defence.
The term as used herein " oligosaccharides " refer to the degree of polymerization (DP) be 2 to 250, preferably DP be 2 to 100, more preferable 2 to 60, even more preferably 2 to 10 carbohydrate.If the alimentation composition of the present invention includes the oligosaccharides that DP is 2 to 100, this causes Composition containing the oligosaccharides that DP is 2 to 5, DP is 50 to 70 and DP is 7 to 60.The term used in the present invention " can not disappear Change oligosaccharides " refer to not by being present in the effect of acid or digestive ferment in people's upper digestive tract (such as small intestine and stomach) in enteron aisle quilt Digestion, but the oligosaccharides preferably to be fermented by people's intestinal microbiota.For example, sucrose, lactose, maltose and maltodextrin are recognized To be digestible.
Preferably, indigestible oligosaccharides of the invention are soluble.It is used herein when referring to polysaccharide, fiber or oligosaccharides Term " soluble " mean according to L.Prosky et al., J.Assoc.Off.Anal.Chem.71,1017-1023 (1988) method recorded, the substance are at least soluble.
In the method for the present invention or on the way, the indigestible oligosaccharides for including in alimentation composition of the invention preferably include The mixture of indigestible oligosaccharides.Indigestible oligosaccharides are preferably selected from oligofructose, such as inulin;Indigestible dextrin;It is oligomeric Galactolipin, such as transgalactooligosac,harides;Xylo-oligosaccharide, arabinoxylan oligosaccharide (arabino-oligosaccharide), Arab Galactooligosaccharide (arabinogalacto-oligosaccharide), glucose oligosaccharide (gluco-oligosaccharide), Oligomeric dragon gallbladder sugar (gentio-oligosaccharide), mannan oligosaccharide (glucomanno-oligosaccharide), half Newborn manna oligosacchride (galactomannooligosaccharide), manna oligosacchride, oligoisomaltose, nigero-oligosaccharide (nigero-oligosaccharide), mannan oligosaccharide (glucomanno-oligosaccharide), chitosan oligosaccharide (chito- Oligosaccharide), soyabean oligosaccharides (soy oligosaccharide), oligosaccharide (uronic acid oligosaccharide);Sialyloligosaccharide (sialyloligosaccharide), such as 3- sialyl lactoses (3-SL), 6- Sialyl lactose (6-SL), sialyl lactose tetrose a, b, c (LST), two sialyl lactose N tetroses (DSLNT), sialyl lactose N six sugared (sialyl-lactoNhexaose) (S-LNH), DS-LNH;And oligomeric fucose, such as (not) sulphation rock algae Polysaccharide oligosaccharides (fucoidan oligosaccharide), 2'-Fucosyl lactose (2 '-FL), 3- fucosyllactoses (3- FL), two fucosyllactose, lacto-iV-fucopentaose (lacto-N-fucopenatose) (LNFP) I, II, III, V, breast The new rock algae pentoses (Lacto-N-neofucopenaose) (LNnFP) of sugar-N- ,-six sugar (Lacto- of two fucosidos of lactose-N- N-difucosyl-hexaose) (LNDH) and its mixture are even more preferably selected from oligofructose, such as inulin;Oligomeric gala Sugar, such as transgalactooligosac,harides;With fucose and its mixture, even more preferably transgalactooligosac,harides and/or inulin, most It is preferred that transgalactooligosac,harides.In the composition of the present invention or an embodiment of method, indigestible oligosaccharides are selected from anti- Formula galactooligosaccharide, oligofructose and its mixture.
Indigestible oligosaccharides are preferably selected from β-galactooligosaccharide, alpha-galactooligosaccharide and galactan (galactan).Root According to further preferred embodiment, indigestible oligosaccharides are β-galactooligosaccharide.Preferably, indigestible oligosaccharides include have β (1, 4), the galactooligosaccharide of β (1,3) and/or β (1,6) glycosidic bond and terminal glucose.Transgalactooligosac,harides for example can be with commodity NameGOS(Domo FrieslandCampina Ingredients),Bi2muno(Clasado),Cup-oligo (Nissin Sugar) and Oligomate55 (Yakult) are obtained.These oligosaccharides increase sIgA levels and increase to a greater extent Strong mucosa-immune defence activity.
Indigestible oligosaccharides preferably include oligofructose.In other cases, oligofructose can have such as levulan (fructopolysaccharide), oligofructose (oligofructose), polyfructosan (polyfructose), poly- fruit are poly- The title of sugared (polyfructan), inulin, levulan (levan) and levulan (fructan), and can refer to include β-connection Fructose units oligosaccharides, be preferably 2 to 200 by β (2,1) and/or β (2,6) glucosides key connections and preferred DP.It is preferred that Ground, oligofructose contain the glucose of end β (2,1) glucosides key connection.Preferably, oligofructose contains at least seven β-connection Fructose units.In another preferred embodiment, using inulin.Inulin is a kind of oligofructose, wherein at least 75% Glycosidic bond be β (2,1) key.In general, the average chain length of inulin is 8 to 60 monosaccharide units.It is suitable for the invention composition Oligofructose can be with trade nameHP (Orafti) is commercially available.Other suitable sources are Raftilose (Orafti), Fibrulose and Fibruline (Cosucra) and Frutafit and Frutalose (Sensus).
Preferably, alimentation composition of the invention includes the mixture of galactooligosaccharide and oligofructose.Preferably, oligomeric Galactolipin and the mixture of oligofructose with 1/99 to 99/1, it is more preferable 1/19 to 19/1, more preferable 1/1 to 19/1, more preferably 2/1 to 15/1, the weight ratio for being more preferably 5/1 to 12/1, even more preferably 8/1 to 10/1, even more preferably about 9/1 exists. When galactooligosaccharide with low average DP and oligofructose with relatively high DP when, which is particularly advantageous. Most preferably galactooligosaccharides of the averagely DP less than 10, preferably shorter than 6 and average DP are higher than 7, are preferably higher than 11, even more excellent The mixture of oligofructose of the choosing higher than 20.This mixture collaboration increases sIgA levels and enhances mucosa-immune defence activity.
Preferably, alimentation composition of the invention includes the mixture of short chain oligofructose and long chain fructo-oligosaccharides.It is preferred that The mixture of ground, short chain oligofructose and long chain fructo-oligosaccharides with 1/99 to 99/1, it is more preferable 1/19 to 19/1, even more preferably 1/10 to 19/1, more preferable 1/5 to 15/1, more preferable 1/1 to 10/1 weight ratio exists.Preferably be averaged DP less than 10, The oligofructose of preferably shorter than 6 short chain oligofructose and average DP higher than 7, preferably higher than 11, even more preferably more than 20 Mixture.
The alimentation composition of the present invention includes 2.5 to 20 weight %, more preferable 2.5 to 15 weight %, even more excellent in total Select the indigestible oligosaccharides of 3.0 to 10 weight %, most preferably 5.0 to 7.5 weight %, the dry weight meter based on alimentation composition.Base It is counted in 100ml, alimentation composition of the invention preferably comprises 0.35 to 2.5 weight %, more preferable 0.35 to 2.0 weight in total The indigestible oligosaccharides of %, even more preferably 0.4 to 1.5 weight % are measured, 100ml alimentation composition meters are based on.Relatively low amount is not It is poor that oligosaccharides effect in terms of stimulation sIgA formation or mucosa-immune defence can be digested, and excessively high amount can then lead to abdominal distension and abdomen The side effect of portion's discomfort.
Alimentation composition
Alimentation composition used according to the invention can be considered as also pharmaceutical composition, be preferably suitable for baby to Medicine.The preferred enteral administration of alimentation composition of the present invention is more preferably administered orally.
The alimentation composition of the present invention is preferably infant formula, second stage formulation (follow on formula) Or growth is newborn (growing up milk).The alimentation composition of the present invention can be advantageously used for the complete nutrient of baby.It is preferred that Ground, alimentation composition of the invention are infant formula.Infant formula is defined as the formulation for baby, and for example may be used For the initial formula object for 0 to 6 or 0 to 4 month infant.Second stage formulation is used for the baby at 4 or 6 monthly ages to 12 monthly ages Youngster.Growth breast is used for the children at 12 to 36 monthly ages.The composition of the present invention preferably comprises lipid composition, protein component and carbon water Compound component, and preferably give in liquid form.The alimentation composition of the present invention can also be the form of dry food, preferably Powder type, with the explanation for mixing the dry food (preferably powder) with suitable liquid (preferably water).According to The alimentation composition that the present invention uses preferably comprises other compositions, such as vitamin, minerals, trace element and other micro battalion Element is supported, to become complete nutritional composition.Instructed according to the world, preferably infant formula include vitamin, it is minerals, micro- Secondary element and other micronutrients.
The alimentation composition of the present invention preferably comprises lipid, protein and digestible carbohydrate, and wherein lipid provides The 5 to 50% of total calorie, protein provides the 5 to 50% of total calorie, and digestible carbohydrate provides the roads Zong Ka In 15 to 90%.Preferably, in the alimentation composition of the present invention, lipid provides the 35 to 50% of total calorie, protein The 7.5 to 12.5% of total calorie are provided, and digestible carbohydrate provides the 40 to 55% of total calorie.In order to calculate Protein accounts for the percentage of total calorie, needs the gross energy for considering to be provided by protein, peptide and amino acid.Preferably, 3 are provided To 7g lipids/100kcal alimentation compositions, preferably 4 to 6g/100kcal alimentation compositions;There is provided 1.6 to 4g protein/ 100kcal alimentation compositions, preferably 1.75 to 2.5g/100kcal alimentation compositions, and offer 5 to 20g can digest carbon aquation Conjunction object/100kcal alimentation compositions, preferably 8 to 15g/100kcal alimentation compositions.Preferably, alimentation composition of the invention Include 4 to 6g lipid/100kcal, 1.6 to 1.9g protein/100kcal, more preferable 1.75 to 1.85g protein/ 100kcal and 8 to 15g digestible carbohydrates/100kcal alimentation compositions.In one embodiment, per 100kcal Alimentation composition provides 3 to 7g lipids, and 4 are preferably provided per 100kcal alimentation compositions to 6g lipids;Per 100kcal nutrition groups It closes object and provides 1.6 to 2.1g protein, 1.6 are preferably provided per 100kcal alimentation compositions to 2.0g protein;And it is every 100kcal alimentation compositions provide 5 to 20g digestible carbohydrates, preferably provide 8 to 15g per 100kcal alimentation compositions Digestible carbohydrate, and wherein preferably digestible carbohydrate component includes at least lactose of 60 weight %, base In total digestible carbohydrate meter, the lactose of more preferably at least 75 weight %, even more desirably at least 90 weight % are based on Total digestible carbohydrate meter.The total amount of calorie is by coming from protein, lipid, digestible carbohydrate and can not disappear The summation for changing the calorie of oligosaccharides determines.
The alimentation composition of the present invention preferably comprises digestible carbohydrate component.Preferred digestible carbohydrate Group is divided into lactose, glucose, sucrose, fructose, galactolipin, maltose, starch and maltodextrin.Lactose is present in human milk Main digestible carbohydrate.The alimentation composition of the present invention preferably comprises lactose.Due to the alimentation composition of the present invention Including the fermented ingredient obtained by lactic acid producing bacteria fermentation, therefore the amount of lactose is reduced relative to its source due to fermentation, It is converted into lactate and/or lactic acid by lactose fermenters.Therefore, it in the preparation of the alimentation composition of the present invention, is preferably added to Lactose.Preferably, alimentation composition of the invention does not include a large amount of carbohydrate in addition to lactose.With can digest carbon aquation Close object such as maltodextrin, sucrose, glucose, maltose and other digestible carbohydrate phases with hyperglycemic index Than lactose has lower glycemic index, is therefore preferred.The alimentation composition of the present invention, which preferably comprises, can digest carbon aquation Close object, wherein at least 35 weight %, more preferably at least 50 weight %, more preferably at least 60 weight %, more preferably at least 75 weights The digestible carbohydrate for measuring %, even more desirably at least 90 weight %, most preferably at least 95 weight % is lactose.Based on dry Restatement, alimentation composition of the invention preferably comprise at least the lactose of 25 weight %, preferably at least 40 weight %, more preferably at least The lactose of 50 weight %.
The alimentation composition of the present invention preferably comprises at least a kind of selected from animal lipid (not including people's lipid) and vegetable butter The lipid of matter.Preferably, composition of the invention includes vegetable lipid and at least one selected from fish oil, animal oil, algae oil, fungi The combination of oily (fungal oil) and the oil of bacterium oily (bacterial oil).The present invention alimentation composition preferably provide 3 to 7g lipids/100kcal alimentation compositions preferably provide 4 to 6g lipids/100kcal alimentation compositions.When in liquid form for example When as instant liquid, alimentation composition preferably comprises 2.1 to 6.5g lipids/100ml, and more preferable 3.0 to 4.0g/100ml.Base In dry weight meter, alimentation composition of the invention preferably comprises the lipid of 12.5 to 40 weight %, more preferable 19 to 30 weight %.It is excellent Selection of land, lipid include essential fatty acid alpha-linolenic acid (ALA), linoleic acid (LA) and/or long-chain polyunsaturated fatty acid (LC- PUFA).LC-PUFA, LA and/or ALA can be used as free fatty, as a triglyceride, triglyceride form, monoglyceride Form, phospholipid form are provided as above-mentioned one or more mixtures.Preferably, alimentation composition of the invention includes At least one, preferably at least two kinds of Lipid sources selected from the following:Rapeseed oil (such as rape oil (colza oil), canola Oil and canola oil), high oleic sunflower oil, high oleic safflower oil, olive oil, marine oil (marine oil), microbial oil, coconut palm Seed oil, palm-kernel oil and butterfat.The alimentation composition of the present invention is not human milk.
The alimentation composition of the present invention preferably comprises protein.The protein used in alimentation composition is preferably selected from inhuman Animal protein, preferably lactoprotein;Vegetable protein, such as preferred soybean protein and/or rice protein;And its mixture.This hair Bright alimentation composition preferably comprises casein and/or lactalbumin, more preferable milk albumin and/or ox casein.Therefore, In one embodiment, the protein in alimentation composition of the invention includes the albumen selected from lactalbumin and casein Matter, preferred whey albumen and casein, preferably lactalbumin and/or casein come from cow's milk.Preferably, protein includes small In free amino acid, dipeptides, tripeptides or the aminosal of 5 weight %, it is based on gross protein meter.The alimentation composition of the present invention Preferably comprise casein and lactalbumin, casein:The weight ratio of lactalbumin is 10:90 to 90:10, more preferable 20:80 to 80:20, even more preferably 35:65 to 55:45.
According to Kjeldahl's method, 6.38 conversion factor or right is used by measurement total nitrogen and in the case of casein 6.25 conversion factor is used in other protein in addition to casein, the dry weight meter of the alimentation composition based on the present invention, Calculate the weight % of protein.The term " protein " used in the present invention or " protein component " refer to protein, peptide and trip The summation of isolated amino acid.
The alimentation composition of the present invention preferably comprises 1.6 to 4.0g protein/100kcal alimentation compositions, preferably every 100kcal alimentation compositions provide 1.6 to 3.5g, even more preferably 1.75 to 2.5g protein.In one embodiment, The alimentation composition of the present invention includes 1.6 to 2.1g protein/100kcal alimentation compositions, preferably per 100kcal nutrient combinations Object provides 1.6 to 2.0g, more preferable 1.75 to 2.1g, even more preferably 1.75 to 2.0g protein.In an embodiment In, the amount of the protein that alimentation composition of the invention includes is less than 2.0g/100kcal, and preferably 1.6 to 1.9g, it is even more excellent It selects 1.75 to 1.85g/100kcal alimentation compositions.It will lead to baby and children based on the total calorie of too low protein content of meter The growth and development of youngster are insufficient.When in liquid form for example as instant liquid when, alimentation composition preferably comprise 0.5 to 6.0g protein/100ml, more preferable 1.0 to 3.0g protein/100ml, even more preferably 1.0 to 1.5g protein/100ml, Most preferably 1.0 to 1.3g protein/100ml.Based on dry weight meter, alimentation composition of the invention preferably comprises 5 to 20 weight % Protein, the preferably at least protein of 8 weight %, the dry weight meter based on total alimentation composition, more preferable 8 to 14 weight %'s Protein, the even more preferably protein of 8 to 9.5 weight %, the dry weight meter based on total alimentation composition.
In order to meet the calorie demand of baby or child, alimentation composition preferably comprises 45 to 200kcal/100ml liquid Body.For baby, alimentation composition is more preferably with 60 to 90kcal/100ml liquid, even more preferably 65 to 75kcal/ 100ml liquid.This caloric density ensures the optimal proportion between water and calorie consumption.For child --- 12 to 36 months The human experimenter in age, alimentation composition more preferably with 45 to 65 caloric density, even more preferably 50 to 60kcal/ 100ml.The present invention composition Morie osmolarity be preferably 150 to 420mOsmol/L, more preferable 260 to 320mOsmol/L.Low Morie osmolarity is further intended to reduce gastrointestinal pressure.
When alimentation composition is liquid form, the preferred volume given daily is daily about 80 to 2500ml, more preferably About 200 to 1200ml.Preferably, daily feeding number is 1 to 10, preferably 3 to 8.In one embodiment, daily with liquid Body form gives alimentation composition, continues at least 2 days, preferably at least 4 weeks, preferably at least 8 weeks, more preferably at least 12 weeks, wherein The total volume given daily be 200ml to 1200ml, and wherein daily feeding number be 1 to 10.
When in liquid form, alimentation composition of the invention preferably have 1 to 60mPa.s, preferably 1 to 20mPa.s, more It is preferred that 1 to 10mPa.s, most preferably 1 to 6mPa.s viscosity.Low viscosity ensures that liquid appropriate is given, for example, fitting through whole A nipple.The viscosity is also very similar to the viscosity of human milk.In addition, low viscosity leads to normal gastric emptying and better energy Intake, this is required to needing baby of the energy for optimum growh and development.The composition of the present invention is preferably by by powder Last shape composition is mixed with water to prepare.In general, infant formula is prepared in this way.Therefore, the invention further relates to one kind The powder composition of packaging, wherein the packaging be provided with powder mix to obtain with appropriate amount of fluid viscosity for 1 to The explanation of the liquid composition of 60mPa.s.Use 300 (Physica Messtechnik of Physica Rheometer MCR GmbH, Ostfilden, Germany) at 20 DEG C with 95s-1Shear rate measure liquid viscosity.
Using
In the context of the present invention, " prevention " of disease or certain illness, which is still meant that, suffers from the disease or " the wind of certain illness Danger reduces ", and still mean that in " treatment of the people of risk " for suffering from the disease or certain illness.
It was found by the inventors of the present invention that after the alimentation composition for eating the present invention, the horizontal collaboration of sIgA increases.This table Bright mucosa-immune system of defense is improved.
With give not comprising selected from bifidobacterium breve and/or streptococcus thermophilus non-replicating lactic acid producing bacteria and can not disappear The alimentation composition for changing the combination of oligosaccharides is compared, and observes that effect as described herein, the i.e. mucous membrane that sIgA increases and/or improves are exempted from Epidemic disease system.It was found that compared with standard infant formula object fed infant, these observed effects are also closer in human milk The level observed in fed infant.
Unexpectedly, these synergies cannot be construed in composition between indigestible oligosaccharides and lactic acid producing bacteria Direct interaction, reason is that bacterium is inactivated;Can not be construed to increased enteric microorganism activity, reason be with Intestinal pH does not have apparent correlation.
In one embodiment, alimentation composition of the invention is used to increase the IgA of the human experimenter at 0 to 36 monthly age Secretion.In one embodiment, alimentation composition of the invention is used to increase the human experimenter, even more at 0 to 18 monthly age It is preferred that the IgA secretions of 12 monthly ages baby below, the even more preferably baby at 0 to 6 monthly age.In one embodiment, this hair Bright alimentation composition be used for increase by 12 to 36 monthly ages child IgA secrete, most preferably 18 to 30 or to 24 monthly ages child IgA secretion.Preferably, alimentation composition of the invention is additionally operable to provide nutrition for the human experimenter.The battalion of the present invention The preferred enteral of composition is supported to give, it is more preferably oral to give.
In one embodiment, alimentation composition of the invention is used to improve the glutinous of the human experimenter at 0 to 36 monthly age Film immune defense.In one embodiment, alimentation composition of the invention be used for improve 0 to 18 monthly age human experimenter, The mucosa-immune of even more preferably 12 monthly ages baby below, the even more preferably baby at 0 to 6 monthly age are defendd.Implement at one In scheme, the mucosa-immune that alimentation composition of the invention is used to improve the child at 12 to 36 monthly ages is defendd, and most preferably 18 to 30 Or the mucosa-immune defence of the child to 24 monthly ages.Preferably, alimentation composition of the invention is additionally operable to as the human subjects Person provides nutrition.The preferred enteral of alimentation composition of the present invention is given, more preferably oral to give.
In preferred embodiments, method of the invention or purposes are used for the baby of vaginal delivery.
In preferred embodiments, method of the invention or purposes are used for full-term newborn infant, are preferred for the mature of health Baby.
Herein and its in claims, verb "comprising" and its deformation are used with its non-limiting meaning, it is intended that packet The subsequent project of the word is included, but is not excluded for the project being not specifically mentioned.In addition, the member drawn by indefinite article "a" or "an" Element does not exclude the presence of the possibility of more than one element, there is one and only one element unless the context clearly requires otherwise.Therefore, Indefinite article "a" or "an" generally means that "at least one".Weight % means weight percent.
Embodiment
Embodiment 1:Including non-replicating lactic acid producing bacteria selected from bifidobacterium breve and streptococcus thermophilus and indigestible Synergy of the infant formula of oligosaccharides to baby's secretory IgA level
It is random, double blind, control, in parallel group, perspective, polycentric, multinational, intervention study, will be by Examination person is coequally randomly divided into four treatment groups.In addition, (will never receive any infant formula by Pure breast feeding since birth Object) and its mother have intention continue Pure breast feeding until the baby at baby's at least 4 monthly ages be included in breast-feeding refer to group.In total 350 subjects enter group, wherein 280 subjects are given any one of four kinds of test products at random, and 70 tested Person is put into breast-feeding and refers to group.
Test group 1:Infant formula 1 is the baby based on cow's milk of the improvement of the 0-6 month infants for bottle feeding Formulation (Nutrilon 1 is sold by Dutch Nutricia).Formulation contains indigestible oligosaccharides (NDO) --- oligomeric gala Sugar is (purchased from FrieslandCampina Domo'sGOS, average degree of polymerization (are purchased from less than 6) with oligofructose The RaftilinHP of Orafti, average degree of polymerization are higher than 20) with about 9:1 w/w than mixture, in an amount of from about 0.8g/ 100ml.Formulation does not include the non-replicating lactic acid producing bacteria selected from bifidobacterium breve and/or streptococcus thermophilus.Formulation is also Not comprising science lactic acid producing bacteria.
Test group 2:Infant formula 2 is the baby based on cow's milk of the improvement of the 0-6 month infants for bottle feeding Formulation, and be the Partial fermentation for including bacterial strain bifidobacterium breve CNCM 1-2219 and streptococcus thermophilus CNCM 1-1620 Infant formula(being sold by Gallia, France), the bacterial strain is inactivated after fermentation process by heat, bacterium Fermentating metabolism object is such as L- (+) lactic acid.The amount of Pfansteihl salt is higher than 0.05 weight %, the dry weight meter based on composition.Do not add Add NDO.During the fermentation, the galactooligosaccharide of the amount based on about 2 weight % of dry weight meter is generated by streptococcus thermophilus.Not replicated Type bifidobacterium breve and the equivalent of streptococcus thermophilus are higher than 5.107cfu/g.The amount of science bifidobacterium breve and streptococcus thermophilus Less than 1.103cfu/g。
Test group 3:Infant formula 3 is experiment test formulation, and is the 0-6 month infants for bottle feeding The infant formula based on cow's milk of improvement.Formulation contains the indigestible oligosaccharides (average polymerization of the amount of about 0.9g/100ml Oligofructose (Raftilin-HP for being purchased from Orafti) of galactooligosaccharide of the degree less than 6 and average degree of polymerization higher than 20 mixes Close object), and include the infant formula of the fermentation such as in the IF 2 of test group 2It (is sold by French Gallia It sells).The amount of the galactooligosaccharide of addition considers the amount of the galactooligosaccharide generated due to the effect of streptococcus thermophilus.
Control group:Infant formula 4 is control formula object:The improvement of 0-6 month infants for bottle feeding based on The infant formula of cow's milk, without indigestible oligosaccharides and without the not replicated selected from bifidobacterium breve and/or streptococcus thermophilus Type lactic acid producing bacteria, and be free of science lactic acid producing bacteria.
All four test formulations objects all include nucleotide and the fat blend containing long chain fatty acids.Formulation is in card It is similar in terms of content, protein content, fat blend in road, and the digestible carbohydrate with analog quantity.According to For the international instruction 2006/141/EC of infant formula, formulation also include vitamin, minerals, trace element and other Micronutrient.
At the end of the study, 198 randomized subjects complete research, and 82 randomized subjects prematurely exit and grind Study carefully.Effective test product group is compared with control group, ahead of time the conspicuousness of the quantity and property of bolter not statistically Difference.For demography and baseline characteristic, subject is balanced well in seminar.
When medical every time, fecal sample is collected into the faeces container provided by Nutricia Research by parent. Sample directly freezed and is kept at this temperature until giving sample to researcher by parent after collecting at -20 DEG C.Existing , sample is stored at -80 DEG C and is used for subsequent analysis.In each collect, 2 pipes must be filled with half.If due to grinding The practical problem needs for studying carefully scene can arrange other transports and storing mode.Fecal excretion is measured with standard laboratory techniques Type IgA is horizontal.Since the sIgA distributions measured show potential deflection, for statistical analysis, tested using ANOVA Logarithmic transformation has been carried out before difference between seminar.Based on geometrical mean (effect quantity=due to logarithmic transformation table Be shown as geometric average than group difference) to sIgA levels carry out statistical analysis.
As a result it is shown in table 1.In order to analyze initial data, ITT analyses are considered as the Main Analysis of the research.4 When a month --- period of the still complete feeding infant formula of baby ---, 3 groups of IF is (thin comprising non-replicating lactic acid producing The experimental formula object of bacterium and indigestible oligosaccharides) with 4 control groups of IF or the excrement sIgA levels in 2 groups of IF (Calisma) Between there is significant difference (p&lt statistically;0.05).When compared with 1 group of IF (Nutrilon), there are trend (p= 0.07).When IF 1 is when IF 2, IF 1 are compared with IF 4, or when IF 2 is compared with IF 4, not no conspicuousness statistically Difference.
When compared with the reference group with breast-feeding, do not provide statistical data, reason be reference group not and be it is random, Therefore it should not be used to the direct comparison with random research group.The statistical analysis of intermediate value is not carried out, but observes similar mould Formula.
The difference that sIgA between test group 3 and 4 is generated is represented by the effect quantity based on geometrical mean, is equal to 1.65.This can be construed to:When compared with the control group for using IF 4, caused using experimental formula object IF 3 at 4 monthly age SIgA concentration increase about 65%.Similarly, test group 3 is 1.53 relative to the effect quantity of test group 1, and test group 3 is opposite In test group 2 effect quantity be 2.06.
SIgA concentration in the group of edible IF 3, which is synergistically higher than, is expected, based on edible IF 1 and IF 2 and control IF 4 Group as a result, and being valuably more closely similar to the level observed in the reference group of breast-feeding.This shows to exempt from mucous membrane Epidemic disease defence has collaboration to increase effect.
Since bacterium present in IF 3 (and IF 2) is inactivated by heat, this effect cannot be construed to be originated from formulation Enteron aisle lactic acid producing bacteria amount increase, can not be construed to these from formulation lactic acid producing bacterias to being added not The increase of the intestinal fermentation of oligosaccharides can be digested.
Table 1:SlgA concentration (μ the g/g)-ITT crowds of excrement when medical every time
* compared to test IF 3p<0.05
#Compared to test IF 3:P=0.07
Embodiment 2:The edible non-replicating lactic acid producing bacteria comprising selected from bifidobacterium breve and streptococcus thermophilus and can not The infant formula for digesting oligosaccharides increases enteron aisle sIgA levels
In random, polycentric, double blind, prospective clinical trial, baby enters group before 28 ages in days, and is referred to Surely receive a kind of until 17 week old in three kinds of formulations:
Test group 1:Infant formula 1 include per 100ml 66kcal, 1.35g protein (milk albumin/casein, Weight ratio be 1/1), 8.2g digestible carbohydrates (wherein 5.6g lactose and 2.1g maltodextrins), 3.0g fat it is (main Plant fat), 0.8g include weight ratio be 9:1 (the sources scGOS) and (sources lcFOS GOS) indigestible oligosaccharides.Based on dry weight meter, about 50% is originated from the infant formula LactofidusTM, a kind of commercially available infant formula with trade name Gallia sale.LactofidusTMIt is a kind of hair Kefir milk derivative composition, prepares by with streptococcus thermophilus fermentation, and includes bifidobacterium breve.Using mild heat treatment To make lactic acid producing bacteria inactivate.The amount of non-replicating lactic acid producing bacteria selected from bifidobacterium breve and streptococcus thermophilus is more than 107Cfu/g dry weights.The amount of streptococcus thermophilus is about 104To 105Cfu/g dry weights.Infant formula includes to be based on dry weight meter about Lactic acid+lactate of 0.55 weight %, wherein at least 95% is L (+)-lactic acid/lactate.Referred to according to the world of infant formula It also includes vitamin, minerals, trace element and other micronutrients to enable 2006/141/EC, composition.
Test group 2:Infant formula 2, is similar to infant formula 1, but without 0.8g indigestible oligosaccharides scGOS and lcFOS。
Test group 3:Infant formula 3, a kind of standard infant formula object including 0.8g indigestible oligosaccharides, it is described can not It is 9 that digestion oligosaccharides, which is weight ratio,:1 (the sources scGOS) and (sources lcFOS GOS), and And rest part has similar composition with infant formula 1.The formulation does not include bifidobacterium breve and/or thermophilus Bacterium.
At baseline and after intervening 17 weeks, in a manner of similar to described in embodiment 1 collecting fecal specimens is used for Physiology and microbiologic analysis.The only sample of subject group of the analysis with one group of complete fecal specimens (going to a doctor twice) Product, wherein excrement amount are sufficient for all analyses.In addition, eliminating the sample from following baby:After birth whenever The baby for the thickener being added in formulation is used using any systemic antibiotics or during research.
In one group of selected fecal specimens, infant formula used is assessed to secretory immunoglobulin A (sIgA) Influence, the results are shown in Table 2.
Equally, sIgA concentration is higher than the group for eating infant formula 2 or 3 in the group of edible experiment infant formula 1 SIgA concentration, the result being very similar in embodiment 1.This shows to increase the influence that mucosa-immune is defendd.
Enjoyably, inconsistent with the influence to excrement pH to the influence that excrement sIgA is horizontal.In edible infant formula 2 PH is minimum in group, and pH is medium in the group of edible experiment infant formula 1.PH reflects the activity of intestinal microbiota. The lower excrement pH of test group 1 and 2 be attributed to test infant formula present in indigestible oligosaccharides fermentation, and It ferments in test group 2 highest, and the horizontal highests of sIgA in test group 1.
Table 2:The sIgA concentration (μ g/g) of excrement when medical every time
WIn order to analyze, Wilcoxon rank sum tests (W) are used, this is because violating normality assumption and/or there are different Constant value.
* the interested comparison for being tested:IF 1 and IF 3, there are conspicuousness difference (p&lt between group;0.05).
#For the interested comparison tested:IF 1 and IF 2, there are conspicuousness difference (p&lt between group;0.05).

Claims (12)

1. at least one non-replicating lactic acid producing bacteria bacterial strain and indigestible widow selected from bifidobacterium breve and streptococcus thermophilus Purposes of the sugar in preparing alimentation composition, the alimentation composition are used to increase IgA points of the human experimenter at 0 to 36 monthly age It secretes, wherein the alimentation composition includes the indigestible oligosaccharides of 2.5 to the 15 weight % of dry weight meter based on alimentation composition.
2. at least one non-replicating lactic acid producing bacteria bacterial strain and indigestible widow selected from bifidobacterium breve and streptococcus thermophilus Purposes of the sugar in preparing alimentation composition, the alimentation composition are used to improve the mucous membrane of the human experimenter at 0 to 36 monthly age Immune defense, wherein the alimentation composition includes the indigestible of 2.5 to the 15 weight % of dry weight meter based on alimentation composition Oligosaccharides.
3. purposes according to any one of the preceding claims, wherein the alimentation composition includes the short bifid of non-replicating Bacillus.
4. purposes according to any one of the preceding claims, wherein the alimentation composition includes the short bifid of non-replicating Bacillus and/or streptococcus thermophilus, amount are equal at least about 107The dry weight of cfu/g alimentation compositions, more preferably at least 108Cfu/g is dry Weight.
5. purposes according to any one of the preceding claims, wherein bifidobacterium breve and/or streptococcus thermophilus are inactivated To less than 106The dry weight of cfu/g alimentation compositions, more preferably less than 105It is the dry weight of cfu/g alimentation compositions, even more preferably low In 103The level of the dry weight of cfu/g alimentation compositions.
6. purposes according to any one of the preceding claims is infant formula, second stage formulation or growth Breast.
7. purposes according to any one of the preceding claims, wherein the indigestible oligosaccharides are selected from oligofructose, no It can peptic dextrin, galactooligosaccharide, xylo-oligosaccharide, arabinoxylan oligosaccharide, Arabic galactooligosacchari(es, glucose oligosaccharide, oligomeric rough gentian Sugar, mannan oligosaccharide, galactomannan-oligosaccharide, manna oligosacchride, oligoisomaltose, nigero-oligosaccharide, mannan oligosaccharide, shell are few Sugar, soyabean oligosaccharides, oligosaccharide, sialyloligosaccharide and oligomeric fucose and its mixture.
8. purposes according to any one of the preceding claims, wherein the indigestible oligosaccharides include galactooligosaccharide And/or oligofructose.
9. purposes according to any one of the preceding claims, wherein the alimentation composition includes by bifidobacterium breve And/or the fermented ingredient of streptococcus thermophilus fermentation, and the wherein described alimentation composition includes 0.05 to 1.5 weight %'s in total L (+)-lactic acid and L (+)-lactate.
10. purposes according to any one of the preceding claims, wherein the alimentation composition includes protein, can digest Carbohydrate and lipid, and 1.6 to 4g protein/100kcal alimentation compositions are wherein provided, providing 5 to 20g can digest Carbohydrate/100kcal alimentation compositions, and 3 to 7g lipids/100kcal alimentation compositions are provided.
11. a kind of method of the IgA secretions of human experimenter increasing by 0 to 36 monthly age comprising give human experimenter's one kind Including at least one non-replicating lactic acid producing bacteria bacterial strain selected from bifidobacterium breve and streptococcus thermophilus and include indigestible The alimentation composition of oligosaccharides, the composition are indigestible with 2.5 to the 15 weight % of dry weight meter based on alimentation composition Oligosaccharides.
12. a kind of method of the mucosa-immune defence of human experimenter improving for 0 to 36 monthly age comprising give human experimenter It is a kind of comprising at least one non-replicating lactic acid producing bacteria bacterial strain selected from bifidobacterium breve and streptococcus thermophilus and include can not Digest oligosaccharides alimentation composition, the composition with 2.5 to the 15 weight % of dry weight meter based on alimentation composition can not Digest oligosaccharides.
CN201680082809.0A 2015-12-29 2016-12-29 Nutrient formulation object containing indigestible oligosaccharides and non-replicating lactic acid producing bacteria Pending CN108697141A (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
EP15202858.5 2015-12-29
EP15202858 2015-12-29
PCT/EP2016/082848 WO2017114901A1 (en) 2015-12-29 2016-12-29 Nutritional formula with non-digestible oligosaccharides and non-replicating lactic acid producing bacteria

Publications (1)

Publication Number Publication Date
CN108697141A true CN108697141A (en) 2018-10-23

Family

ID=55068877

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201680082809.0A Pending CN108697141A (en) 2015-12-29 2016-12-29 Nutrient formulation object containing indigestible oligosaccharides and non-replicating lactic acid producing bacteria

Country Status (3)

Country Link
EP (1) EP3397075A1 (en)
CN (1) CN108697141A (en)
WO (1) WO2017114901A1 (en)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113015440A (en) * 2018-11-01 2021-06-22 N·V·努特里奇亚 Nutritional composition comprising urea and indigestible oligosaccharides
CN113163835A (en) * 2019-05-15 2021-07-23 N·V·努特里奇亚 Fermentation formula for promoting intestinal development
CN113423288A (en) * 2019-02-04 2021-09-21 N·V·努特里奇亚 Fermented formula containing non-digestible oligosaccharides for sleep improvement

Citations (23)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH0464063A (en) * 1990-07-03 1992-02-28 Sapporo Breweries Ltd Method for detecting contamination bacteria of food
US20020182600A1 (en) * 2001-04-11 2002-12-05 Smith Jack V. Method for assaying biological and other constituents using synthetic nucleounits in lateral flow, liquid, and dry chemistry techniques
KR20030091247A (en) * 2002-05-25 2003-12-03 이현철 Non-oral vaccine for preventing dental caries using mannose-coated polymeric micelle-immunoregulator-immunogen complex
US20030232396A1 (en) * 2002-02-22 2003-12-18 Biolife Solutions, Inc. Method and use of protein microarray technology and proteomic analysis to determine efficacy of human and xenographic cell, tissue and organ transplant
CN1554250A (en) * 2003-12-29 2004-12-15 石家庄三鹿集团股份有限公司 SOD milk powder
CN1589405A (en) * 2001-11-20 2005-03-02 斯达高诊断公司 Method for detecting analyte(s) using magnetic colloidal particles
JP2005068092A (en) * 2003-08-26 2005-03-17 Ala:Kk Composition for immunostimulation
JP2006067881A (en) * 2004-09-01 2006-03-16 Nichimo Co Ltd New lactic acid bacterium and lactic acid bacterium preparation
CN101043904A (en) * 2004-08-24 2007-09-26 N·V·努特里奇亚 Nutritional composition comprising indigestible oligosaccharides
CN101049162A (en) * 2007-05-21 2007-10-10 北京东方兴企食品工业技术有限公司 Nutrition protein powder containing beneficial bacteria
CN101144064A (en) * 2007-09-03 2008-03-19 江南大学 Lactobacillus brevis with anti-mutagenesis active and capable of producing exopolysaccharide and use thereof
CN101218942A (en) * 2008-02-02 2008-07-16 内蒙古蒙牛乳业（集团）股份有限公司 Serum albumin added liquid condition milk for baby
JP2008533002A (en) * 2005-03-08 2008-08-21 フォンテラ コ−オペレイティブ グループ リミティド High pressure treatment of bioactive compositions
CN101278688A (en) * 2008-05-22 2008-10-08 澳大利亚迪唯恩乳业有限公司 Infant nutrition immunity formula milk powder and method of preparing the same
EP2093573A2 (en) * 2008-01-31 2009-08-26 Hitachi High-Technologies Corporation Automatic analyzer
CN101795579A (en) * 2006-08-04 2010-08-04 Shs国际有限公司 Protein free formula
CN101801220A (en) * 2007-06-15 2010-08-11 努特里希亚公司 nutrition with non-viable bifidobacterium and non-digestible oligosaccharide
CN102065867A (en) * 2008-06-13 2011-05-18 N.V.努特里奇亚 Nutrition for prevention of infections
CN102076360A (en) * 2008-06-24 2011-05-25 雀巢产品技术援助有限公司 Probiotics, secretory IgA and inflammation
CN102159226A (en) * 2008-07-21 2011-08-17 雀巢产品技术援助有限公司 Probiotics to increase iga secretion in infants born by caesarean section
CN103497861A (en) * 2013-08-30 2014-01-08 靳建伟 Preparation method of thick wine
CN103637219A (en) * 2013-12-27 2014-03-19 浙江贝因美科工贸股份有限公司 Probiotics composition as well as application and infant food thereof
WO2014201037A2 (en) * 2013-06-10 2014-12-18 New York University Methods for manipulating immune responses by altering microbiota

Patent Citations (25)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH0464063A (en) * 1990-07-03 1992-02-28 Sapporo Breweries Ltd Method for detecting contamination bacteria of food
US20020182600A1 (en) * 2001-04-11 2002-12-05 Smith Jack V. Method for assaying biological and other constituents using synthetic nucleounits in lateral flow, liquid, and dry chemistry techniques
CN1589405A (en) * 2001-11-20 2005-03-02 斯达高诊断公司 Method for detecting analyte(s) using magnetic colloidal particles
US20030232396A1 (en) * 2002-02-22 2003-12-18 Biolife Solutions, Inc. Method and use of protein microarray technology and proteomic analysis to determine efficacy of human and xenographic cell, tissue and organ transplant
KR20030091247A (en) * 2002-05-25 2003-12-03 이현철 Non-oral vaccine for preventing dental caries using mannose-coated polymeric micelle-immunoregulator-immunogen complex
JP2005068092A (en) * 2003-08-26 2005-03-17 Ala:Kk Composition for immunostimulation
CN1554250A (en) * 2003-12-29 2004-12-15 石家庄三鹿集团股份有限公司 SOD milk powder
CN101043904A (en) * 2004-08-24 2007-09-26 N·V·努特里奇亚 Nutritional composition comprising indigestible oligosaccharides
JP2006067881A (en) * 2004-09-01 2006-03-16 Nichimo Co Ltd New lactic acid bacterium and lactic acid bacterium preparation
JP2008533002A (en) * 2005-03-08 2008-08-21 フォンテラ コ−オペレイティブ グループ リミティド High pressure treatment of bioactive compositions
CN104012838A (en) * 2006-08-04 2014-09-03 努特里希亚公司 Non-allergenic ingredients and food products
CN101795579A (en) * 2006-08-04 2010-08-04 Shs国际有限公司 Protein free formula
CN101049162A (en) * 2007-05-21 2007-10-10 北京东方兴企食品工业技术有限公司 Nutrition protein powder containing beneficial bacteria
CN101801220A (en) * 2007-06-15 2010-08-11 努特里希亚公司 nutrition with non-viable bifidobacterium and non-digestible oligosaccharide
CN101144064A (en) * 2007-09-03 2008-03-19 江南大学 Lactobacillus brevis with anti-mutagenesis active and capable of producing exopolysaccharide and use thereof
EP2093573A2 (en) * 2008-01-31 2009-08-26 Hitachi High-Technologies Corporation Automatic analyzer
CN101218942A (en) * 2008-02-02 2008-07-16 内蒙古蒙牛乳业（集团）股份有限公司 Serum albumin added liquid condition milk for baby
CN101278688A (en) * 2008-05-22 2008-10-08 澳大利亚迪唯恩乳业有限公司 Infant nutrition immunity formula milk powder and method of preparing the same
CN102065867A (en) * 2008-06-13 2011-05-18 N.V.努特里奇亚 Nutrition for prevention of infections
CN102076360A (en) * 2008-06-24 2011-05-25 雀巢产品技术援助有限公司 Probiotics, secretory IgA and inflammation
CN102159226A (en) * 2008-07-21 2011-08-17 雀巢产品技术援助有限公司 Probiotics to increase iga secretion in infants born by caesarean section
CN102159226B (en) * 2008-07-21 2014-02-26 雀巢产品技术援助有限公司 Probiotics to increase iga secretion in infants born by caesarean section
WO2014201037A2 (en) * 2013-06-10 2014-12-18 New York University Methods for manipulating immune responses by altering microbiota
CN103497861A (en) * 2013-08-30 2014-01-08 靳建伟 Preparation method of thick wine
CN103637219A (en) * 2013-12-27 2014-03-19 浙江贝因美科工贸股份有限公司 Probiotics composition as well as application and infant food thereof

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
MONIKA ROLLER等: "Prebiotic Inulin Enriched with Oligofructose in Combination with the Probiotics Lactobacillus rhamnosus and Bifidobacterium lactis Modulates Intestinal Immune Functions in Rats", 《AMERICAN SOCIETY FOR NUTRITIONAL SCIENCES》 *
YAN ZHONG等: "Protective effect of galactooligosaccharide-supplemented enteral nutrition on intestinal barrier function in rats with severe acute pancreatitis", 《CLINICAL NUTRITION》 *
李伟等: "肠道黏膜免疫屏障及其菌群与机体健康关系的研究进展", 《食品科学》 *

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113015440A (en) * 2018-11-01 2021-06-22 N·V·努特里奇亚 Nutritional composition comprising urea and indigestible oligosaccharides
CN113015440B (en) * 2018-11-01 2024-04-05 N·V·努特里奇亚 Nutritional composition comprising urea and non-digestible oligosaccharides
CN113423288A (en) * 2019-02-04 2021-09-21 N·V·努特里奇亚 Fermented formula containing non-digestible oligosaccharides for sleep improvement
CN113163835A (en) * 2019-05-15 2021-07-23 N·V·努特里奇亚 Fermentation formula for promoting intestinal development

Also Published As

Publication number Publication date
WO2017114901A1 (en) 2017-07-06
EP3397075A1 (en) 2018-11-07

Similar Documents

Publication Publication Date Title
CN102123715B (en) Immune system stimulating nutrition
AU2010293145B2 (en) Probiotic derived non-viable material for allergy prevention and treatment
CN107019701B (en) Methods of using human milk oligosaccharides to reduce the incidence of necrotizing enterocolitis in infants, toddlers, or children
TW201304692A (en) Synbiotic combination of probiotic and human milk oligosaccharides to promote growth of beneficial microbiota
TW201233334A (en) Human milk oligosaccharides to promote growth of beneficial bacteria
CN101917873A (en) Composition with synbiotics
RU2724536C2 (en) Fermented milk mixture with indigestible oligosaccharides
CN105848499A (en) Fermented formula with non digestible oligosaccharides
TW201105252A (en) Prevention and treatment of allergic diarrhoea
CN108697141A (en) Nutrient formulation object containing indigestible oligosaccharides and non-replicating lactic acid producing bacteria
CN112273657A (en) Probiotic composition for preventing or improving allergic diseases, preparation method and application
US20160206658A1 (en) Nutrition for prevention of infections
CN109688839A (en) The infant formula of fermentation
CN109475165A (en) The infant formula of fermentation
CN113423288A (en) Fermented formula containing non-digestible oligosaccharides for sleep improvement
EP3968787A1 (en) Fermented formula for improving intestinal development
WO2019155044A1 (en) Fermented formula with non-digestible oligosaccharides
EP3749328A1 (en) Fermented formula with non-digestible oligosaccharides

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
WD01 Invention patent application deemed withdrawn after publication

Application publication date: 20181023

WD01 Invention patent application deemed withdrawn after publication