CN103338775B - Use human milk oligosaccharides reduces the method for the sickness rate of the necrotizing enterocolitis of baby, child or child - Google Patents

Use human milk oligosaccharides reduces the method for the sickness rate of the necrotizing enterocolitis of baby, child or child Download PDF

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CN103338775B
CN103338775B CN201180067021.XA CN201180067021A CN103338775B CN 103338775 B CN103338775 B CN 103338775B CN 201180067021 A CN201180067021 A CN 201180067021A CN 103338775 B CN103338775 B CN 103338775B
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lnnt
gos
fos
inulin
polydextrose
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CN103338775A (en
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J·周
S·R·戴维斯
R·巴克
G·O·杜斯卡-麦克尤恩
H·K·林克
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Abbott GmbH and Co KG
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Abbott GmbH and Co KG
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Priority to CN201610935257.5A priority Critical patent/CN107019701B/en
Priority claimed from PCT/US2011/067018 external-priority patent/WO2012092156A1/en
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Abstract

The invention discloses use and include that the nutritional composition of human milk oligosaccharides is to the method reducing the necrotizing enterocolitis sickness rate of baby, child or child.This nutritional composition including human milk oligosaccharides can effectively reduce the sickness rate of inflammation and inflammatory diseases.

Description

Human milk oligosaccharides is used to reduce the Necrotizing enterocolitis of baby, child or child The method of scorching sickness rate
Cross-Reference to Related Applications
This application claims U.S. Provisional Application No. 61/428,863 and in December, 2010 filed in December in 2010 31 days The rights and interests of U.S. Provisional Application No. 61/428,868 filed in 31 days, combine in its entire disclosure herein in the way of quoting as proof Hold.
The field of the disclosure
It relates to improve the gastrointestinal function of baby, child and child and the human milk oligosaccharides (HMO) of toleration.More Saying, it relates to comprise the human milk reinforcing agent of HMO, premature labor and term infant formula and child's formula, it can stimulate body Enteric nervous cell in gastrointestinal tract, thus treats and/or prevents disease and the disease that many gastrointestinals are relevant.
The background of the disclosure
During growing after birth, neonatal intestinal experience fully-developed process, finally produce gastrointestinal epithelial tissue, this Plant epithelial tissue and play the effect of selectivity barrier (that is, Gut barrie r).Gastrointestinal epithelial tissue absorbs nutrient, electrolyte and water, Prevent from contacting diet and the antigen of microorganism, including food allergen simultaneously.Specifically, this barrier limited antigen pass through into Enter system circulation, be therefore prevented from infection, inflammatory reaction and other gastrointestinal that may occur during infancy stage and life subsequently Disease and disease.For the most immature baby that immune system and intestinal growth are the most complete, the especially baby of premature labor, shape The intestinal flora becoming suboptimum may cause infection, diarrhoea, allergy and food intolerance.
It is believed that formed and keep barrier to be affected by diet.Breast milk comprises some components, and they not only play disease The effect of substance receptor analogs, but also by baby's enterocyte and/or relevant immunocyte group make immunity because of Son activation, thus promote baby's gastrointestinal and immune formation and growth.
But, not every baby can accept human breast milk.It is therefore desirable to provide nutritional composition and The infant formula especially synthesized, it can produce nutritional benefits, and this benefit includes improving gastrointestinal growth, growing and ripe. Infect and the immunity of other gastrointestinal disease, disease and obstacle, then volume for microorganism if nutritional composition can strengthen Other places is the most useful.
The disclosure is summarized
It relates to nutritional composition, including infant formula, the baby formulas of synthesis and the child of synthesis of synthesis Formula, it includes that at least one HMO, this HMO can be used alone, or with other component such as oligosaccharide probiotics (prebiotic oligosaccharides) and/or probiotic bacteria are combined, for improving baby, child, child or adult Intestinal tube function and immunity, the invention still further relates to the using method being correlated with.More specifically, this nutritional composition can be promoted The g and D of intestinal tube barrier, thus treats and/or prevents the formula caused by the dysfunction of intestinal tube barrier is lost not Toleration or other gastrointestinal disease and/or obstacle.
One embodiment relates to reducing sending out of necrotizing enterocolitis in having the baby of these needs, child or child The method of sick rate.The method includes: gives baby, child or child and comprises total quantity about 0.001 mg/ml to about 20 The compositions of mg/ml human milk oligosaccharides.
Another embodiment relates to reducing necrotizing enterocolitis in having the baby of these needs, child or child The method of sickness rate.The method includes: gives baby, child or child and comprises 6'-saliva lactose (sialyllactose), 2'- The auxotype combination of fucosyllactose (fucosyllactose) and the new tetrose of lactoyl-N-(lacto-N-neotetraose) Thing.
Another embodiment relate to synthesis formula, its in the baby having this to need, child or child for improving Feeding intolerance.The formula of synthesis comprises the oligosaccharide mixture of about 0.2 mg/ml to about 20 mg/ml, and wherein this is low Oligosaccharide mixture comprises: selected from oligofructose (fructooligosaccharide), oligomeric galactose, the new tetrose of lactoyl-N-, 2'-fucosyllactose and the first oligosaccharide of its combination form；Selected from 3'-saliva lactose, 6'-saliva lactose and its combination shape Second oligosaccharide of formula；With selected from inulin, natural gum, polydextrose and its combination form the 3rd oligosaccharide.
Another embodiment relate to synthesis formula, its in the baby having this to need, child or child for improving Feeding intolerance.The formula of synthesis comprises the oligosaccharide mixture of about 0.2 mg/ml to about 20 mg/ml, and wherein this is low Oligosaccharide mixture comprises: selected from oligofructose (fructooligosaccharide), oligomeric galactose, the new tetrose of lactoyl-N-, 2'-fucosyllactose and the first oligosaccharide of its combination form；Selected from 3'-saliva lactose, 6'-saliva lactose and its combination shape Second oligosaccharide of formula.
Another embodiment relates to improving the method feeding toleration in having the baby of these needs, child or child. The method includes: give the battalion that baby, child or child comprise about 0.2 mg/ml to about 20 mg/ml oligosaccharide mixture Supporting type compositions, wherein this oligosaccharide mixture comprises: selected from oligofructose (fructooligosaccharide), oligomeric half Lactose, the new tetrose of lactoyl-N-, 2'-fucosyllactose and the first oligosaccharide of its combination form；Selected from 3'-saliva lactose, 6'-saliva lactose and the second oligosaccharide of its combination form；With selected from inulin, natural gum, polydextrose and the of its combination form Three oligosaccharide.
Another embodiment relates to improving the method feeding toleration in having the baby of these needs, child or child. The method includes: give the conjunction that baby, child or child comprise about 0.2 mg/ml to about 20 mg/ml oligosaccharide mixture The pediatric formula become, wherein this oligosaccharide mixture comprises: selected from oligofructose (fructooligosaccharide), oligomeric Galactose, the new tetrose of lactoyl-N-, 2'-fucosyllactose and the first oligosaccharide of its combination form；Selected from 3'-saliva lactose, 6'-saliva lactose and the second oligosaccharide of its combination form；With selected from inulin, natural gum, polydextrose and the of its combination form Three oligosaccharide.
Have been found that being supplied to the HMO of intestinal tube tissue can stimulate intestinal tube-brain-Immune Axis, and improve immune system and Enteric nervous system.In particular, it has been found that, the enteric nervous cell in 2'-fucosyllactose stimulating gastrointestinal road, can improve Intestinal tube function, and make gastrointestinal problems be minimized.
Further, it has been found that by the mixture giving the carbohydrate that baby, child, child or adult select (including HMO), the digestion toleration of baby, child, child or adult can be significantly increased.Specifically, this carbon aquation Polymer mixtures includes quickly, middling speed and the combination of carbohydrate that slowly digests, and it includes specific HMO, such as lactoyl- The new tetrose of N-, 2'-fucosyllactose, 3'-fucosyllactose, 3'-saliva lactose and/or 6'-saliva lactose.
Furthermore, it has been found that by giving baby, child, child or the compositions of adult's Synbiotics (synbiotic) (including HMO), the integrity of the gut barrier of baby, child, child or adult can be significantly increased.Specifically, should Synbiotics (synbiotic) compositions includes probiotic bacteria, oligomeric galactose and oligofructose (fructooligosaccharide) At least one in (such as, short chain oligofructose (fructooligosaccharide)) and at least one HMO.This Synbiotics (synbiotic) compositions promotes the cluster of useful intestinal microflora, thus stops the growth of noxious bacteria.
Although the most briefly discuss the nutritional composition relevant with premature infant and baby and method, but should This understanding, give the single HMO of child, child and adult or its (such as, oligosaccharide is prebiotic with other component described herein Unit and/or probiotic bacteria) compositions, can be that child, child and adult provide many benefits discussed herein.Specifically, In some embodiments, by means of the nutritional composition using the disclosure to include HMO, can reduce what generally impact was grown up The sickness rate of gastrointestinal disease and obstacle (such as, Crohn disease, irritable bowel syndrome etc.).
The brief description of accompanying drawing
Fig. 1 is the figure describing 2'FL and 3'FL measured in embodiment 35 to the impact of intestinal activeness.
Fig. 2 is the table of the microbiological culture media used in the experiment in vitro listing embodiment 36.
Fig. 3 is to describe pH value time dependent curve when being affected by various oligosaccharide substrates of test in embodiment 36.
When Fig. 4 is that in description embodiment 36, the short-chain fat acid product of test is affected by various oligosaccharide substrates at any time Between change curve.
Fig. 5 describe embodiment 37 evaluate various Bifidobacteriums (Bifidobacterium spp.) growth curve.
Fig. 6 describe embodiment 37 evaluate various Bifidobacteriums (Bifidobacterium spp.) growth curve.
Fig. 7 describe embodiment 37 evaluate various Bifidobacteriums (Bifidobacterium spp.) growth curve.
Fig. 8-10 is that (Pre-confluent) HT-29 epithelial cell divides before the fusion in the presence of LNnT, 2'FL and 6'SL The figure changed.
Figure 11-13 is fusion (Confluent) the HT-29 epithelial cell electrical impedance in the presence of LNnT, 2'FL and 6'SL The figure of (cell resistance).
Figure 14-16 is (Post-confluent) CaCo-2Bbe epithelium after the fusion in the presence of LNnT, 2'FL and 6'SL The figure of cell differentiation.
Figure 17-19 is CaCo-2Bbe epithelial cell sucrase active after the fusion in the presence of LNnT, 2'FL and 6'SL Figure.
Figure 20-22 is CaCo-2Bbe epithelial cell electrical impedance (cell after the fusion in the presence of LNnT, 2'FL and 6'SL Resistance) figure.
Figure 23 A-23E is to be described in embodiment 39 human milk oligosaccharides measured to participating in the one of gastrointestinal tract healing response The impact of the expression of a little genes and the figure of its dose dependent.
The detailed description of the disclosure
Nutritional composition described herein and method are used alone HMO, or other the oligosaccharide benefit with at least one Raw unit and/or probiotic combination use HMO, for control with alleviate many to this disease that intestinal tube-brain-immune system is relevant, Obstacle and disease.These and other feature of this nutritional composition and method, and many optional variable are described in detail below With the part in additive.
Herein, term " steaming and decocting (retort) packaging " and " retort sterilization " can intercourse use, unless otherwise mentioned, Otherwise refer to: load the general practice of container (being most typically canister or other similar packing) with nutritional liquid, Then the packaging to topping up carries out the heat sterilizing step of necessity, forms sterilization, the nutritional liquid product of steaming and decocting packaging.
Unless otherwise noted, terms used herein " aseptic packaging " refers to: need not the life of above-mentioned steaming and decocting packaging step Produce packaging product, before filling, nutritional liquid and packaging are sterilized respectively, then closes under sterilization or aseptic processing conditions And, form sterilization, the nutritional liquid product of aseptic packaging.
Unless otherwise noted, terms used herein " fatty " and " oily " can intercourse use, refer to from planting The lipid matter that thing or animal obtain or process with plant or animal.These terms also include the lipid matter of synthesis, as long as this The material planting synthesis is suitable for being orally administered to the mankind.
Unless otherwise noted, terms used herein " human milk oligosaccharides " or " HMO " are commonly referred to as human breast milk Present in many complex carbohydrates, it can be acid or neutral form, and also refer to its precursor.Exemplary Non-limiting human milk oligosaccharides include 3'-saliva lactose, 6'-saliva lactose, 3'-fucosyllactose, 2'-fucosido breast Sugar and the new tetrose of lactoyl-N-.Exemplary human milk oligosaccharides precursor includes sialic acid and/or fucose.
Unless otherwise noted, terms used herein " storage is stable " refers to: after encapsulation, at 18-24 DEG C The nutritional-based product of commodity stabilization is remained in that after preserving at least 3 months, including preserving about 6 months to about 24 months, And include about 12 months to about 18 months.
Terms used herein " auxotype preparation " or " nutritional composition " can intercourse use, and unless separately make Illustrate, otherwise refer to synthesizing formula, including nutritional liquid, auxotype powder, auxotype solid, auxotype semisolid, battalion Support type semiliquid, auxotype enriching substance and other nutritional type food product any known in the art.Auxotype powder can weigh Group forms nutritional liquid, and they all comprise one or more fat, albumen and carbohydrate, and is suitable for that people is oral to be made With.Term " auxotype preparation " or " nutritional composition " do not include human breast milk (human breast milk).
Unless otherwise noted, liquid form that terms used herein " nutritional liquid " refers to drink immediately, The nutritional composition of conc forms, and auxotype produced by auxotype powder described herein of recombinating before the use Liquid.
Unless otherwise noted, terms used herein " auxotype powder " refers to what mobility or available spoon scooped The nutritional composition of form, before the use, it can be recombinated with water or other waterborne liquid, and include being spray-dried and The powder of dry mixed/dry mix.
Unless otherwise noted, terms used herein " auxotype is semi-solid " refers to that characteristic (such as rigidity) is solid Nutritional-based product between body and liquid.Some semisolid examples include pudding, gelatin and mastic.
Unless otherwise noted, terms used herein " auxotype semiliquid " refers to that characteristic (such as mobility) exists Nutritional-based product between liquid and solid.Some semi-liquid examples include milk shake (thick shakes) and liquid gel.
Unless otherwise noted, terms used herein " baby " refers to 12 months or is less than the people of December.Make herein Term " premature infant " referred to before pregnant 36 weeks the people of birth.
Unless otherwise noted, terms used herein " child " refers to the one-year-old people with up to three years old.
Unless otherwise noted, terms used herein " child " refers to three years old with the people of up to 12 years old.
Unless otherwise noted, terms used herein " neonate " refers to from the people that birth to surrounding is big.
Unless otherwise noted, terms used herein " infant formula " or " infant formula of synthesis " can intersect mutually Change use, and refer to be suitable for liquid, semiliquid, solid and the replacement of semisolid human milk or the succedaneum that baby uses.Close The formula become includes the component of half purification or purified source.Unless otherwise noted, terms used herein " half purification " or " purification " refers to the purification by natural materials or by the material prepared by synthesis.Term " infant formula " and " synthesis Infant formula " do not include human breast milk.
Unless otherwise noted, terms used herein " baby formulas of synthesis " refers to be suitable for maximum 36 months Liquid, semiliquid, solid and semisolid human milk (human milk) that the baby of (3 years old) or child use are replaced or are substituted Product.The formula of synthesis includes the component of half purification or purified source.Unless otherwise noted, " half is pure for terms used herein Change " or " purification " refer to the purification by natural materials or by synthesis prepared by material.Term " the child nutrition of synthesis Formula " do not include human breast milk.
Unless otherwise noted, terms used herein " child's formula of synthesis " refers to be suitable for maximum 12 years old Liquid, semiliquid, solid and semisolid human milk that child uses are replaced or succedaneum.The formula of synthesis includes half purification or pure Change the component in source.Unless otherwise noted, terms used herein " half purification " or " purification " refer to pass through natural goods The purification of matter or by the material prepared by synthesis.Term " the child nutrition formula of synthesis " does not include human breast milk.
Unless otherwise noted, terms used herein " preterm formula " refers to be suitable for the liquid that premature infant uses Body and Solid nutritional type product.
Unless otherwise noted, terms used herein " human milk reinforcing agent " refers to be suitable for and breast milk or premature infant Formula or infant formula mixing and the liquid that consumed by premature labor or term infant and Solid nutritional type product.
Unless otherwise noted, terms used herein " susceptible " and " being in danger " refer to some The resistance of disease or disease is the least, including disease or the genetic predisposition of disease, has disease or the family history of disease and/or has Disease or the symptom of disease.
Unless otherwise noted, terms used herein " cognitive competence " refers to individual study, Memory acquisition and memory Ability.
Unless otherwise noted, terms used herein " growth of virus " or " growth of antibacterial " refer to virus Or the generation of antibacterial, breed or replicate.
Unless otherwise noted, all percentage ratios used herein, number and ratio are the weight by whole compositions Meter.The all this weight relevant with the component listed is based on activity level, therefore, does not includes being purchased that material may contain is molten Agent or by-product, unless otherwise mentioned.
The most specifically disclosing, numerical range used herein includes under each numerical value within the range and numerical value Hyte.Additionally, these numerical rangies should be interpreted as: to any numerical value related in the range of this or the power of the lower hyte of numerical value Profit requires to provide and supports.Such as, it should the disclosure of 1 to 10 is interpreted as: support 2 to 8,3 to 7,5 to 6,1 to 9,3.6 to 4.6, the scope of 3.5 to 9.9 etc..
The single features of all present disclosures mentioned or restriction include corresponding multiple feature or restriction, otherwise also So, unless otherwise mentioned or the context of mentioned content clearly shows that in contrast.
Whole combinations of method used herein or processing step can be carried out in any order, unless otherwise mentioned or institute The context of the combination mentioned clearly shows that in contrast.
This nutritional composition and method can comprise compositions described herein and the major part of method, Yi Jiben Any additional or optional component that is described by literary composition or that use in nutritional composition is applied, or be made up of them, or base It is made up of them on Ben.
Product form
The nutritional composition of the disclosure can according to the preparation of any of or other suitable Orally taken product form and Give.Any solid, semisolid, liquid, semiliquid or powder product form, including a combination thereof or version, be suitable for this Literary composition uses, and condition is, this form can make the oral delivery to individual key component defined herein and any optional components be Safely effectively.
Preferably, the nutritional composition of the disclosure is formulated as diet product form defined herein, such as, product shape Containing those embodiments of the component of the disclosure in formula, this product form contains in fat, albumen and carbohydrate At least one, it is preferable that is possibly together with vitamin, mineral or its combination form.In order to prepare nutritional composition, auxotype combines Thing comprises at least one HMO, and comprises at least two or multiple HMO when many, it is preferable that HMO and albumen, fat, dimension At least one combination in raw element and mineral.
As described below, in order to provide single Major Nutrient source or extra-nutrition source, or in order to be suffered from disease specific, barrier Hinder or the individuality of disease provides specific nutritional composition or offer to have the nutritional composition of target nutritional benefits, this battalion Support type compositions to prepare together with the nutrient of enough kinds and quantity.
The concrete limiting examples of the product form being suitable for the compositions containing HMO disclosed herein includes, Such as, liquid and powdered nutritional type enriching substance, liquid and powder human milk reinforcing agent, liquid and powder preterm formula, liquid and Powder infant formula, liquid and powder constituent and half key element (semi-elemental formulas) formula, liquid and powder Virgin formula, liquid and powder baby formulas, liquid and powder subsequent segment formula (follow-on formulas), it is suitable for suffering from food The liquid of individual use of product intolerance, allergy, dysimmunity and other gastrointestinal disease, disease and/or obstacle, powder With solid adult's nutrient formulation.
Nutritional liquid
Nutritional liquid includes the nutritional liquid concentrating and can drinking immediately.Most typically these nutritional liquids are joined It is made as suspension or emulsion, although other liquid form is also within the scope of the disclosure.
The auxotype emulsion being suitable for using can be the water-based emulsion containing albumen, fat and carbohydrate.These breasts Liquid is typically flowable or drinkable liquid, and typically oil-in-water, Water-In-Oil at about 1 DEG C to about 25 DEG C Or composite water soluble emulsion form, although this emulsion most typically ground is the O/w emulsion with continuous aqueous phase and discontinuous oil phase Form.
This auxotype emulsion can be and typically bin stability emulsion.Auxotype emulsion typically contain to The water of many about 95% weight, including the water of about 50% to about 95% weight, also includes about 60% to about 90% weight Water, also includes the water of about 70% to about 85% weight.Auxotype emulsion can have various product density, but most typically ground has There is the density more than about 1.03 g/ml, including more than about 1.04 g/ml, including more than about 1.055 g/ml, including big About 1.06 g/ml to about 1.12 g/ml, and include about 1.085 g/ml to about 1.10 g/ml.
This auxotype emulsion can have the heat density (caloric density) of applicable end user's nutritional need, Although in most of the cases, this emulsion generally comprises at least 19 kilocalories/ounce fluid ounce (660 kilocalorie/liter), the most greatly About 20 kilocalories/ounce fluid ounce (675-680 kilocalorie/liter) to about 25 kilocalories/ounce fluid ounce (820 kilocalorie/liter), the most more allusion quotation About 20 kilocalories/ounce fluid ounce (675-680 kilocalorie/liter) type to about 24 kilocalories/ounce fluid ounce (800-810 kilocalorie/ Rise).Generally, 22-24 kilocalorie/ounce fluid ounce formula is more commonly used for the baby of premature labor or low birth weight, 20-21 kilocalorie/liquid Amount ounce (675-680 to 700 kilocalorie/liter) formula is more frequently utilized for term infant.In some embodiments, emulsion can have The heat density of about 50-100 kilocalorie/rise to about 660 kilocalories/liter, including about 150 kilocalories/rise to about 500 kilocalories/ Rise.In some specific embodiments, emulsion can have the heat density of 25 or 50 or 75 or 100 kilocalories/liter.
This auxotype emulsion can have a pH value of about 3.5 to about 8, but most preferably, about 4.5 to about 7.5 Scope, including the scope of about 5.5 to about 7.3, including the scope of about 6.2 to about 7.2.
Although the offer amount of auxotype emulsion (serving size) can change according to many variablees, but typically carries For amount generally at least about 1 mL, or the most about 2 mL, or the most about 5 mL, or the most about 10 ML, or the most about 25 mL, including the scope of about 2 mL to about 300 mL, including about 4 mL to about 250 ML, including about 10 mL to about 240 mL.
Auxotype solid
Auxotype solid can be any solid form, but the most flowable or the most flowable granule group Solvate form, or at least particulate composition.Specifically, suitable auxotype solid product form includes being spray-dried, gathering Collection and/or the powder composition of dry mixed.Said composition can easily use bale-out, and easily with spoon or similar other Apparatus measures, and target user can be formed immediately easily by suitable waterborne liquid (typically water) restructuring said composition It is administered orally or the nutritional composition of enteral use.In this respect, " immediately " uses and typically refers to use within about 48 hours, Most typically ground, within about 24 hours, the most just uses after restructuring.
Auxotype powder can be recombinated with water before use, reaches to be suitable for the heat density of the nutritional need of end user, Although in most of the cases, powder is recombinated with water, form the group containing at least 19 kilocalories/ounce fluid ounce (660 kilocalorie/liter) Compound, the most about 20 kilocalories/ounce fluid ounce (675-680 kilocalorie/liter) to about 25 kilocalories/ounce fluid ounce (820,000 Card/liter), the most more it is typically about 20 kilocalories/ounce fluid ounce (675-680 kilocalorie/liter) to about 24 kilocalories/liquid measure big belly Department (800-810 kilocalorie/liter).Generally, 22-24 kilocalorie/ounce fluid ounce formula is more commonly used for the baby of premature labor or low birth weight Youngster, 20-21 kilocalorie/ounce fluid ounce (675-680 to 700 kilocalorie/liter) formula is more frequently utilized for term infant.In some embodiments In, restructuring powder can have the heat density of about 50-100 kilocalorie/rise to about 660 kilocalories/liter, including about 150,000 Block/rise to about 500 kilocalories/liter.In some specific embodiments, emulsion can have 25 or 50 or 75 or 100 kilocalories/liter Heat density.
Human milk oligosaccharides (HMO)
The nutritional composition of the disclosure includes at least one HMO, in many embodiments, including two or more The combination form of HMO.Oligosaccharide is one of key component of human breast milk, every liter of breast milk averagely contain 10 grams of neutral oligosaccharide and Every liter contains 1 gram of acidic oligomer sugar.The composition structure of HMO is the most complicated, it is known that the various oligosaccharides structures having more than 200 kinds.
HMO can be separately included in nutritional composition, or in some embodiments, with described herein other Component (such as, oligosaccharide probiotics, probiotic bacteria, etc.) combination.In many embodiments, HMO and other component bags many Include in nutritional composition.Can separate or be enriched with HMO from the milk of mammal secretes, mammal includes but does not limits In: people, cattle, sheep, pig or goat.Process, chemosynthesis or a combination thereof method can also be urged to prepare by fermentable, enzyme HMO。
Neutral oligosaccharide, acidic oligomer sugar, N-acetyl group is may include that for the suitable HMO of this nutritional composition Glucosylation oligosaccharide and HMO precursor.Can be with the tool of HMO that is independent or that be included in the compositions of the disclosure with combination form Body non-limitative example includes: sialic acid (that is, free sialic acid, the sialic acid of lipid binding, protein bound sialic acid)；D- Glucose (Glc)；D-galactose (Gal)；N-acetyl-glucosamine (GlcNAc)；L-fucose (Fuc)；Fucosido oligosaccharide (that is, lactose-N-rock algae pentasaccharides I；Lactose-rock algae pentasaccharides II；2'-fucosyllactose；3'-fucosyllactose；Lactose-N- Rock algae pentasaccharides III；Lactose-N two rock algae six sugar I；And lactodifucotetraose)；Non-fucosylation, non-sialylated oligomeric Sugar (that is, lacto-N-tetraose and the new tetrose of lactoyl-N-)；Sialic acid oligosaccharide (that is, 3'-sialic acid-3-fucosyllactose；Double New six sugar of sialic acid list fucose lactose-N-；Single fucose list saliva lactose-N-eight sugar (sialic acid Lea)；Saliva lactose-N- Rock algae six sugar II；Double saliva lactose-N-rock algae pentasaccharides II；The double saliva lacto-N-tetraose of single fucose)；With sialic acid fucose Base oligosaccharide (that is, 2'-saliva lactose；2-saliva lactose amine；3'-saliva lactose；3'-saliva lactose amine；6'-saliva lactose； 6'-saliva lactose amine；Saliva lactoyl-N-new tetrose c；Single saliva lactose-N-six sugar；Double saliva lactose-N-six sugar I；Single saliva The new six sugar I of lactose-N-；The new six sugar II of single saliva lactose-N-；New six sugar of double saliva lactose-N-；Double saliva lacto-N-tetraose；Double Saliva lactose-N-six sugar II；Saliva lacto-N-tetraose a；Double saliva lactose-N-six sugar I；With saliva lacto-N-tetraose b).Also Can use other variant, wherein glucose (Glc) reducing end by N-acetyl-glucosamine substitute (such as, 2'-fucosido- N-acetyl-glucosamine (2'-FLNac)) be exactly the variant of this 2'-fucosyllactose).U.S. Patent application No. 2009/ 0098240 has been more fully described these HMO, combines entire contents herein in the way of quoting as proof.The disclosure can be included in Compositions in other suitable example of HMO include: lactose-N-rock algae pentasaccharides V, lactose-N-six sugar, p-lactose-N-six Sugar, new six sugar of lactose-N-, new six sugar of p-lactose-N-, single fucosyllactose-N-six sugar II, the fucosylation breast of isomery Sugar-N-six sugar (1), the fucosylation lactose-N-six sugar (3) of isomery, the fucosylation lactose-N-six sugar (2) of isomery, two New six sugar of fucosido-p-lactose-N-, two fucosidos-p-lactose-N-six sugar, two fucosyllactose-N-six sugar, breast New eight sugar (neoocataose) of sugar-N-, p-lactose-N-eight sugar (octanose), isolactose-N-eight sugar, lactose-N-eight sugar, Single fucosyllactose-new eight sugar (neoocataose), single fucosyllactose-N-eight sugar (ocataose), two fucosidos Lactose-N-eight sugar I, two new eight sugar (neoocataose) II of fucosyllactose-N-eight sugar II, two fucosyllactose-N-, New eight sugar (neoocataose) I, lactose-N-ten sugar of two fucosyllactose-N-, new eight sugar of three fucosyllactose-N-, three Fucosyllactose-N-eight sugar, three fucosidos-isolactose-N-eight sugar, lactose-N-two rock algae-six sugar II, sialic acid-breast Sugar-N-tetrose a, sialic acid-lacto-N-tetraose b, sialic acid-lacto-N-tetraose c, sialic acid-fucosido-lactose-N-four Sugar I, sialic acid-fucosido-lacto-N-tetraose II and two sialic acides-lacto-N-tetraose, and its combination form.It is particularly suitable Nutritional composition include at least one following HMO or HMO precursor: sialic acid (SA)；2'-saliva lactose (2'SL)；3'- Saliva lactose (3'SL)；6'-saliva lactose (6'SL)；2'-fucosyllactose (2'FL)；3'-fucosyllactose (3'FL)； With lacto-N-tetraose and the new tetrose of lactoyl-N-(LNnT), especially, the combination of at least one in 2'FL Yu 6'SL and 3'SL Form；Combination form with at least one in LNnT Yu 6'SL and 3'FL.
Other exemplary combination form includes: SA, 3'SL, 6'SL, 3'FL, 2'FL and LNnT；3'SL、6'SL、3'FL、 2'FL and LNnT；SA, 6'SL, 3'FL, 2'FL and LNnT；SA, 3'SL, 3'FL, 2'FL and LNnT；SA、3'SL、6'SL、2'FL And LNnT；SA, 3'SL, 6'SL, 3'FL and LNnT；SA, 3'SL, 6'SL, 3'FL and 2'FL；SA and 3'SL；SA and 6'SL；SA and 2'FL；SA and LNnT；SA, 3'SL and 6'SL；SA, 3'SL and 3'FL；SA, 3'SL and 2'FL；SA, 3'SL and LNnT；SA、6'SL And 3'FL；SA, 6'SL and 2'FL；SA, 6'SL and LNnT；SA, 3'FL and 2'FL；SA, 3'FL and LNnT；SA, 2'FL and LNnT； SA, 3'SL, 6'SL and 3'FL；SA, 3'SL, 6'SL and 2'FL；SA, 3'SL, 6'SL and LNnT；SA, 3'SL, 3'FL and 2'FL； SA, 3'SL, 3'FL and LNnT；SA, 3'SL, 2'FL and LNnT；SA, 6'SL, 3'FL and 2'FL；SA, 6'SL, 2'FL and LNnT； SA, 6'SL, 3'FL and LNnT；SA, 3'FL, 2'FL and LNnT；SA, 6'SL, 2'FL and LNnT；SA, 3'SL, 3'FL, 2'FL and LNnT；SA, 6'SL, 3'FL, 2'FL and LNnT；SA, 3'SL, 6'SL, 3'FL and LNnT；SA, 3'SL, 3'FL, 2'FL and LNnT； SA, 3'SL, 6'SL, 2'FL and LNnT；3'SL, 6'SL, 3'FL and 2'FL；3'SL, 6'SL, 2'FL and LNnT；3'SL、3'FL、 2'FL and LNnT；3'SL, 6'SL, 3'FL and LNnT；3'SL, 6'SL and 3'FL；3'SL, 3'FL and 2'FL；3'SL, 2'FL and LNnT；3'SL, 6'SL and 2'FL；3'SL, 6'SL and LNnT；3'SL and 3'FL；3'SL and 2'FL；3'SL and LNnT；6'SL and 3'FL；6'SL and 2'FL；6'SL and LNnT；6'SL, 3'FL and LNnT；6'SL, 3'FL, 2'FL and LNnT；3'FL, 2'FL and LNnT；3'FL and LNnT；With 2'FL and LNnT.
The HMO being present in nutritional composition total quantity (the mg number of the HMO in every ml compositions) in the composition At least about 0.001 mg/ml, including at least about 0.01 mg/ml, including about 0.001 mg/ml to about 20 mg/ Ml, including about 0.01 mg/ml to about 20 mg/ml, including about 0.001 mg/ml to about 15 mg/ml, including big About 0.01 mg/ml is to about 15 mg/ml, including about 0.001 mg/ml to about 10 mg/ml, including about 0.01 Mg/ml to about 10 mg/ml, including about 0.001 mg/ml to about 5 mg/ml, including about 0.01 mg/ml to about 5 mg/ml, including about 0.001 mg/ml to about 1 mg/ml (the total HMO in nutritional composition), including about 0.001 Mg/ml to about 0.23 mg/ml, including about 0.01 mg/ml to about 0.23 mg/ml.Typically, HMO is in auxotype group Quantity in compound depends on the quantity of other component in existing concrete HMO and nutritional composition.
In a specific embodiment, when nutritional composition is auxotype powder, HMO is in this auxotype powder Total concentration be about 0.0005% to about 5%, (calculate by the weight of auxotype powder) including about 0.01% to about 1%.
In another embodiment, when nutritional composition is the nutritional liquid that can drink immediately, HMO exists Total concentration in this nutritional liquid that can drink immediately is of about 0.0001% to about 0.50%, including about 0.001% to greatly About 0.15%, including about 0.01% to about 0.10%, also include about 0.01% to about 0.03% (by the battalion that can drink immediately The weight supporting type liquid calculates).
In another embodiment, when nutritional composition is the nutritional liquid concentrated, HMO is in this concentration Nutritional liquid in total concentration be of about 0.0002% to about 0.60%, including about 0.002% to about 0.30%, including About 0.02% to about 0.20%, farther include about 0.02% to the about 0.06% (weight by the nutritional liquid concentrated Calculate).
In a specific embodiment, nutritional composition includes neutral human milk oligosaccharides, and quantity is of about 0.001 Mg/ml to about 20 mg/ml, including 0.01 mg/ml to about 20 mg/ml, including about 0.001 mg/ml to less than 2 Mg/ml, including about 0.01 mg/ml to less than 2 mg/ml.
In a specific embodiments of the disclosure, nutritional composition includes 2'FL.2'FL can be uniquely to include HMO in nutritional composition, or other extra HMO can also be included in this nutritional composition (such as, at some In specific embodiments, 2'FL can be combined with 3'SL and/or 6'SL).In one embodiment, this nutritional composition bag Including 2'FL, quantity is of about 0.001 mg/ml to about 20 mg/ml, including about 0.01 mg/ml to about 20 mg/ml, Including about 0.001 mg/ml to less than 2 mg/ml, including about 0.01 mg/ml to less than 2 mg/ml.Implement at another In scheme, this nutritional composition includes that 2'FL, quantity are of about 0.001 mg/ml to about 20 mg/ml, including about 0.01 mg/ml to about 20 mg/ml, including more than 2.5 mg/ml to about 20 mg/ml, including more than 2.5 mg/ml extremely About 15 mg/ml, including more than 2.5 mg/ml to about 10 mg/ml.
In a specific embodiment, nutritional composition includes single 6'SL or its combination shape with other HMO Formula, quantity is of about 0.001 mg/ml to about 20 mg/ml, including about 0.01 mg/ml to about 20 mg/ml, including About 0.001 mg/ml is to less than 0.25 mg/ml, including about 0.01 mg/ml to less than 0.25 mg/ml.Real at another Executing in scheme, nutritional composition includes single 6'SL or its combination form with other HMO, and quantity is of about 0.001 Mg/ml to about 20 mg/ml, including about 0.01 mg/ml to about 20 mg/ml, including more than 0.4 mg/ml to about 20 mg/ml, including more than 0.4 mg/ml to about 15 mg/ml, including more than 0.4 mg/ml to about 10 mg/ml.
In one embodiment, when nutritional composition includes 6'SL, HMO total amount in this nutritional composition Including at least about 88% (based on HMO gross weight) 6'SL, including about 88% (based on HMO gross weight) to about 96% (based on HMO gross weight) 6'SL, including about 88% (based on HMO gross weight) to about 100% (based on HMO gross weight) 6'SL, including big About 100% (based on HMO gross weight) 6'SL.
In another embodiment, nutritional composition includes single 3'SL or its combination form with other HMO, Quantity is of about 0.001 mg/ml to about 20 mg/ml, including about 0.01 mg/ml to about 20 mg/ml, including about 0.001 mg/ml is to less than 0.15 mg/ml, including about 0.01 mg/ml to less than 0.15 mg/ml, including more than 0.25 Mg/ml to about 20 mg/ml, including more than 0.25 mg/ml to about 15 mg/ml, including more than 0.25 mg/ml to about 10 mg/ml。
In one embodiment, when nutritional composition includes 3'SL, HMO total amount in this nutritional composition Including at least about 85% (based on HMO gross weight) 3'SL, including about 85% (based on HMO gross weight) to about 88% (based on HMO gross weight) 3'SL, including about 88% (based on HMO gross weight) to about 100% (based on HMO gross weight) 3'SL, including big About 100% (based on HMO gross weight) 3'SL.
In a specific embodiment, nutritional composition includes single LNnT or its combination shape with other HMO Formula, quantity is of about 0.001 mg/ml to about 20 mg/ml, including about 0.01 mg/ml to about 20 mg/ml, including About 0.001 mg/ml is to less than 0.2 mg/ml, including about 0.01 mg/ml to less than 0.2 mg/ml, including more than 0.32 Mg/ml to about 20 mg/ml, including more than 0.32 mg/ml to about 15 mg/ml, including more than 0.32 mg/ml to about 10 mg/ml。
Other oligosaccharide probiotics
In addition to above-mentioned HMO, the nutritional composition of the disclosure can also comprise other oligosaccharide probiotics (herein In, the total amount of oligosaccharide refers to " oligosaccharide mixture " of this nutritional composition).Suitable for this nutritional composition Other oligosaccharide probiotics source include: be suitable for oral nutrient type compositions and the main component with this compositions Any oligosaccharide probiotics with feature compatibility.In some embodiments, nutritional composition includes one or more HMO and Or the combination form of multiple other oligosaccharide probiotics so that said composition provides synergistic benefits for end user, such as, improves The synergistic benefits of Infants'feeding intolerance.
In some embodiments, it is provided that the HMO of cooperative effect includes with the combination form of other oligosaccharide probiotics: The oligosaccharide (" middling speed of other oligosaccharide probiotics (" rapid fermentation oligosaccharide ") of HMO and rapid fermentation, moderate rate fermentation Fermentation oligosaccharide ") and/or the oligosaccharide (" ferment at a slow speed oligosaccharide ") that ferments at a slow speed.Certain preferred embodiments provides battalion Foster type compositions, it includes at least one HMO and rapid fermentation oligosaccharide, middling speed fermentation oligosaccharide and/or ferments at a slow speed oligomeric The combination form of sugar.
Non-limitative example bag for other oligosaccharide probiotics suitable of nutritional composition described herein Including: have the oligosaccharide probiotics of the degree of polymerization (DP) of at least 2 monosaccharide units, it is deposited in people's upper digestive tract (small intestinal stomach function regulating) Acid or digestive enzyme effect under in intestinal the most digested or the most digested, but it can be fermented by people's intestinal flora. Term " monosaccharide units " refers to the unit with closed-loop structure, preferably hexose, such as, and pyranose or furanose form.In these public affairs In the nutritional composition opened with HMO associated with especially preferred oligosaccharide include: oligomeric galactose (GOS), oligofructose (fructooligosaccharides) (FOS), short chain oligofructose (fructooligosaccharides), inulin, poly-Portugal Grape sugar (PDX), hydrolyzed pectin thing and gum fibre.In a specific embodiment, gum fibre is arabic gum.
The total quantity of the oligosaccharide mixture being present in nutritional composition is at least about 0.001 mg/ml, including At least about 0.01 mg/ml, including at least about 0.1 mg/ml, including at least about 1 mg/ml, including about 0.001 Mg/ml to about 20 mg/ml, including about 1 mg/ml to about 20 mg/ml, including about 1 mg/ml to about 15 mg/ Ml, including about 1 mg/ml to about 10 mg/ml, including about 1 mg/ml to about 5 mg/ml, including about 2 mg/ml To about 20 mg/ml.In one embodiment, the total quantity of the oligosaccharide mixture being present in nutritional composition is About 1 mg/ml to about 4 mg/ml.
Typically, when as oligosaccharide mixture, in addition to HMO, this nutritional composition also includes at least one The oligosaccharide of the oligosaccharide of rapid fermentation, at least one middling speed fermentation and optional at least one oligosaccharide fermented at a slow speed, thus The nutritional composition (that is, reducing flatulence and/or stool frequency) that premature labor and term infant can more preferably tolerate is provided.Rapid fermentation Oligosaccharide be generally of more than 4,000 μ g/g dries/hour fermenting speed；The oligosaccharide of middling speed fermentation is generally of 1, 500 μ g/g dries/hour to 4,000 μ g/g dries/hour fermenting speed；The oligosaccharide fermented at a slow speed is generally of little In 1,500 μ g/g dries/hour fermenting speed.
Illustrate with instantiation, the oligosaccharide of rapid fermentation include FOS, GOS (about 9,304 μ g/g dries/hour), LNnT (about 4,488 μ g/g dries/hour), 2'FL (about 4,872 μ g/g dries/hour) and its combination form.In The oligosaccharide of speed fermentation includes 6'SL (about 1,809 μ g/g dries/hour), 3'SL, 2'FL, 3'FL, LNnT and its combination Form.The oligosaccharide fermented at a slow speed includes: long chain carbohydrates, such as inulin (about Isosorbide-5-Nitrae 35 μ g/g dry/hour), Gum fibre (such as, arabic gum (about 785 μ g/g dries/hour)) and its combination form.
When using in oligosaccharide mixture, the oligosaccharide of rapid fermentation can be included in nutritional composition, number Amount is of about 0.05 mg/ml to about 20 mg/ml, including about 0.5 mg/ml to about 15 mg/ml, including about 0.5 Mg/ml to about 10 mg/ml, including about 1 mg/ml to about 15 mg/ml, including about 1 mg/ml to about 10 mg/ Ml, including about 2 mg/ml to about 8 mg/ml, also includes about 3 mg/ml to about 5 mg/ml.It is oligomeric that middling speed is fermented Sugar can be included in nutritional composition, and quantity is of about 0.05 mg/ml to about 20 mg/ml, including about 0.05 Mg/ml to about 15 mg/ml, including about 0.05 mg/ml to about 10 mg/ml, including about 0.05 mg/ml to about 5 mg/ml, including about 0.05 mg/ml to about 2.5 mg/ml, including about 0.05 mg/ml to about 1 mg/ml, bag Include about 0.05 mg/ml to about 0.5 mg/ml, including about 0.05 mg/ml to about 0.25 mg/ml.Ferment at a slow speed Oligosaccharide can be included in nutritional composition, and quantity is of about 0.05 mg/ml to about 20 mg/ml, including about 0.05 mg/ml to about 15 mg/ml, including about 0.05 mg/ml to about 10 mg/ml, including about 0.05 mg/ml To about 5 mg/ml, also include about 0.05 mg/ml to about 2.5 mg/ml.
In a specific embodiment, this nutritional composition includes oligosaccharide mixture, this oligosaccharide mixture Including LNnT, 6'SL and inulin, the total quantity of oligosaccharide mixture is of about 0.05 mg/ml to about 20 mg/ml.
In another embodiment, this nutritional composition includes oligosaccharide mixture, and this oligosaccharide mixes Thing includes 2'FL, 6'SL and inulin, and the total quantity of oligosaccharide mixture is of about 0.001 mg/ml to about 20 mg/ml, bag Include about 0.01 mg/ml to about 20 mg/ml.
Other exemplary combination form includes: FOS, GOS, 2'FL, LNnT, 3'SL and 6'SL；FOS、GOS、2'FL、3' SL and 6'SL；FOS, GOS, LNnT, 3'SL and 6'SL；FOS, 2'FL, LNnT, 3'SL and 6'SL；GOS、2'FL、LNnT、3'SL And 6'SL；FOS, GOS, 3'SL and 6'SL；FOS, 2'FL, 3'SL and 6'SL；FOS, LNnT, 3'SL and 6'SL；GOS、2'FL、3' SL and 6'SL；GOS, LNnT, 3'SL and 6'SL；2'FL, LNnT, 3'SL and 6'SL；FOS, 3'SL and 6'SL；GOS, 3'SL and 6' SL；2'FL, 3'SL and 6'SL；LNnT, 3'SL and 6'SL；FOS, GOS, 2'FL, LNnT and 3'SL；FOS, GOS, 2'FL and 3' SL；FOS, GOS, LNnT and 3'SL；FOS, 2'FL, LNnT and 3'SL；GOS, 2'FL, LNnT and 3'SL；FOS, GOS and 3'SL； FOS, 2'FL and 3'SL；FOS, LNnT and 3'SL；GOS, 2'FL and 3'SL；GOS, LNnT and 3'SL；2'FL, LNnT and 3'SL； FOS and 3'SL；GOS and 3'SL；2'FL and 3'SL；LNnT and 3'SL；FOS, GOS, 2'FL, LNnT and 6'SL；FOS、GOS、2' FL and 6'SL；FOS, GOS, LNnT and 6'SL；FOS, 2'FL, LNnT and 6'SL；GOS, 2'FL, LNnT and 6'SL；FOS, GOS and 6'SL；FOS, 2'FL and 6'SL；FOS, LNnT and 6'SL；GOS, 2'FL and 6'SL；GOS, LNnT and 6'SL；2'FL, LNnT and 6'SL；FOS and 6'SL；GOS and 6'SL；2'FL and 6'SL；LNnT and 6'SL.
Further exemplary combination form includes: FOS, GOS, 2'FL, LNnT, 3'SL, 6'SL, inulin, natural gum and poly- Glucose；FOS, GOS, 2'FL, 3'SL, 6'SL, inulin, natural gum and polydextrose；FOS, GOS, LNnT, 3'SL, 6'SL, chrysanthemum Powder, natural gum and polydextrose；FOS, 2'FL, LNnT, 3'SL, 6'SL, inulin, natural gum and polydextrose；GOS、2'FL、LNnT、 3'SL, 6'SL, inulin, natural gum and polydextrose；FOS, GOS, 3'SL, 6'SL, inulin, natural gum and polydextrose；FOS、2'FL、 3'SL, 6'SL, inulin, natural gum and polydextrose；FOS, LNnT, 3'SL, 6'SL, inulin, natural gum and polydextrose；GOS、2' FL, 3'SL, 6'SL, inulin, natural gum and polydextrose；GOS, LNnT, 3'SL, 6'SL, inulin, natural gum and polydextrose；2'FL、 LNnT, 3'SL, 6'SL, inulin, natural gum and polydextrose；FOS, 3'SL, 6'SL, inulin, natural gum and polydextrose；GOS、3' SL, 6'SL, inulin, natural gum and polydextrose；2'FL, 3'SL, 6'SL, inulin, natural gum and polydextrose；LNnT、3'SL、6' SL, inulin, natural gum and polydextrose；FOS, GOS, 2'FL, LNnT, 3'SL, inulin, natural gum and polydextrose；FOS、GOS、2' FL, 3'SL, inulin, natural gum and polydextrose；FOS, GOS, LNnT, 3'SL, inulin, natural gum and polydextrose；FOS、2'FL、 LNnT, 3'SL, inulin, natural gum and polydextrose；GOS, 2'FL, LNnT, 3'SL, inulin, natural gum and polydextrose；FOS、GOS、 3'SL, inulin, natural gum and polydextrose；FOS, 2'FL, 3'SL, inulin, natural gum and polydextrose；FOS, LNnT, 3'SL, chrysanthemum Powder, natural gum and polydextrose；GOS, 2'FL, 3'SL, inulin, natural gum and polydextrose；GOS, LNnT, 3'SL, inulin, natural gum and Polydextrose；2'FL, LNnT, 3'SL, inulin, natural gum and polydextrose；FOS, 3'SL, inulin, natural gum and polydextrose；GOS、 3'SL, inulin, natural gum and polydextrose；2'FL, 3'SL, inulin, natural gum and polydextrose；LNnT, 3'SL, inulin, natural gum and Polydextrose；FOS, GOS, 2'FL, LNnT, 6'SL, inulin, natural gum and polydextrose；FOS, GOS, 2'FL, 6'SL, inulin, tree Glue and polydextrose；FOS, GOS, LNnT, 6'SL, inulin, natural gum and polydextrose；FOS, 2'FL, LNnT, 6'SL, inulin, tree Glue and polydextrose；GOS, 2'FL, LNnT, 6'SL, inulin, natural gum and polydextrose；FOS, GOS, 6'SL, inulin, natural gum and Polydextrose；FOS, 2'FL, 6'SL, inulin, natural gum and polydextrose；FOS, LNnT, 6'SL, inulin, natural gum and polydextrose； GOS, 2'FL, 6'SL, inulin, natural gum and polydextrose；GOS, LNnT, 6'SL, inulin, natural gum and polydextrose；2'FL、 LNnT, 6'SL, inulin, natural gum and polydextrose；FOS, 6'SL, inulin, natural gum and polydextrose；GOS, 6'SL, inulin, natural gum And polydextrose；2'FL, 6'SL, inulin, natural gum and polydextrose；LNnT, 6'SL, inulin, natural gum and polydextrose；FOS、 GOS, 2'FL, LNnT, 3'SL, 6'SL, inulin and natural gum；FOS, GOS, 2'FL, 3'SL, 6'SL, inulin and natural gum；FOS、GOS、 LNnT, 3'SL, 6'SL, inulin and natural gum；FOS, 2'FL, LNnT, 3'SL, 6'SL, inulin and natural gum；GOS、2'FL、LNnT、3' SL, 6'SL, inulin and natural gum；FOS, GOS, 3'SL, 6'SL, inulin and natural gum；FOS, 2'FL, 3'SL, 6'SL, inulin and tree Glue；FOS, LNnT, 3'SL, 6'SL, inulin and natural gum；GOS, 2'FL, 3'SL, 6'SL, inulin and natural gum；GOS、LNnT、3'SL、 6'SL, inulin and natural gum；2'FL, LNnT, 3'SL, 6'SL, inulin and natural gum；FOS, 3'SL, 6'SL, inulin and natural gum；GOS、 3'SL, 6'SL, inulin and natural gum；2'FL, 3'SL, 6'SL, inulin and natural gum；LNnT, 3'SL, 6'SL, inulin and natural gum；FOS、 GOS, 2'FL, LNnT, 3'SL, inulin and natural gum；FOS, GOS, 2'FL, 3'SL, inulin and natural gum；FOS、GOS、LNnT、3'SL、 Inulin and natural gum；FOS, 2'FL, LNnT, 3'SL, inulin and natural gum；GOS, 2'FL, LNnT, 3'SL, inulin and natural gum；FOS、 GOS, 3'SL, inulin and natural gum；FOS, 2'FL, 3'SL, inulin and natural gum；FOS, LNnT, 3'SL, inulin and natural gum；GOS、2' FL, 3'SL, inulin and natural gum；GOS, LNnT, 3'SL, inulin and natural gum；2'FL, LNnT, 3'SL, inulin and natural gum；FOS、3' SL, inulin and natural gum；GOS, 3'SL, inulin and natural gum；2'FL, 3'SL, inulin and natural gum；LNnT, 3'SL, inulin and natural gum； FOS, GOS, 2'FL, LNnT, 6'SL, inulin and natural gum；FOS, GOS, 2'FL, 6'SL, inulin and natural gum；FOS、GOS、LNnT、 6'SL, inulin and natural gum；FOS, 2'FL, LNnT, 6'SL, inulin and natural gum；GOS, 2'FL, LNnT, 6'SL, inulin and natural gum； FOS, GOS, 6'SL, inulin and natural gum；FOS, 2'FL, 6'SL, inulin and natural gum；FOS, LNnT, 6'SL, inulin and natural gum； GOS, 2'FL, 6'SL, inulin and natural gum；GOS, LNnT, 6'SL, inulin and natural gum；2'FL, LNnT, 6'SL, inulin and natural gum； FOS, 6'SL, inulin and natural gum；GOS, 6'SL, inulin and natural gum；2'FL, 6'SL, inulin and natural gum；LNnT, 6'SL, inulin and Natural gum；FOS, GOS, 2'FL, LNnT, 3'SL, 6'SL, inulin and polydextrose；FOS, GOS, 2'FL, 3'SL, 6'SL, inulin and Polydextrose；FOS, GOS, LNnT, 3'SL, 6'SL, inulin and polydextrose；FOS, 2'FL, LNnT, 3'SL, 6'SL, inulin and Polydextrose；GOS, 2'FL, LNnT, 3'SL, 6'SL, inulin and polydextrose；FOS, GOS, 3'SL, 6'SL, inulin and poly-Portugal Grape sugar；FOS, 2'FL, 3'SL, 6'SL, inulin and polydextrose；FOS, LNnT, 3'SL, 6'SL, inulin and polydextrose；GOS、 2'FL, 3'SL, 6'SL, inulin and polydextrose；GOS, LNnT, 3'SL, 6'SL, inulin and polydextrose；2'FL、LNnT、3' SL, 6'SL, inulin and polydextrose；FOS, 3'SL, 6'SL, inulin and polydextrose；GOS, 3'SL, 6'SL, inulin and poly-Portugal Grape sugar；2'FL, 3'SL, 6'SL, inulin and polydextrose；LNnT, 3'SL, 6'SL, inulin and polydextrose；FOS、GOS、2' FL, LNnT, 3'SL, inulin and polydextrose；FOS, GOS, 2'FL, 3'SL, inulin and polydextrose；FOS、GOS、LNnT、3' SL, inulin and polydextrose；FOS, 2'FL, LNnT, 3'SL, inulin and polydextrose；GOS, 2'FL, LNnT, 3'SL, inulin and Polydextrose；FOS, GOS, 3'SL, inulin and polydextrose；FOS, 2'FL, 3'SL, inulin and polydextrose；FOS、LNnT、3' SL, inulin and polydextrose；GOS, 2'FL, 3'SL, inulin and polydextrose；GOS, LNnT, 3'SL, inulin and polydextrose； 2'FL, LNnT, 3'SL, inulin and polydextrose；FOS, 3'SL, inulin and polydextrose；GOS, 3'SL, inulin and poly-Fructus Vitis viniferae Sugar；2'FL, 3'SL, inulin and polydextrose；LNnT, 3'SL, inulin and polydextrose；FOS、GOS、2'FL、LNnT、6'SL、 Inulin and polydextrose；FOS, GOS, 2'FL, 6'SL, inulin and polydextrose；FOS, GOS, LNnT, 6'SL, inulin and poly-Portugal Grape sugar；FOS, 2'FL, LNnT, 6'SL, inulin and polydextrose；GOS, 2'FL, LNnT, 6'SL, inulin and polydextrose；FOS、 GOS, 6'SL, inulin and polydextrose；FOS, 2'FL, 6'SL, inulin and polydextrose；FOS, LNnT, 6'SL, inulin and poly-Portugal Grape sugar；GOS, 2'FL, 6'SL, inulin and polydextrose；GOS, LNnT, 6'SL, inulin and polydextrose；2'FL、LNnT、6' SL, inulin and polydextrose；FOS, 6'SL, inulin and polydextrose；GOS, 6'SL, inulin and polydextrose；2'FL、6'SL、 Inulin and polydextrose；LNnT, 6'SL, inulin and polydextrose；FOS, GOS, 2'FL, LNnT, 3'SL, 6'SL, natural gum and poly- Glucose；FOS, GOS, 2'FL, 3'SL, 6'SL, natural gum and polydextrose；FOS, GOS, LNnT, 3'SL, 6'SL, natural gum and poly- Glucose；FOS, 2'FL, LNnT, 3'SL, 6'SL, natural gum and polydextrose；GOS, 2'FL, LNnT, 3'SL, 6'SL, natural gum and Polydextrose；FOS, GOS, 3'SL, 6'SL, natural gum and polydextrose；FOS, 2'FL, 3'SL, 6'SL, natural gum and polydextrose； FOS, LNnT, 3'SL, 6'SL, natural gum and polydextrose；GOS, 2'FL, 3'SL, 6'SL, natural gum and polydextrose；GOS、LNnT、 3'SL, 6'SL, natural gum and polydextrose；2'FL, LNnT, 3'SL, 6'SL, natural gum and polydextrose；FOS, 3'SL, 6'SL, tree Glue and polydextrose；GOS, 3'SL, 6'SL, natural gum and polydextrose；2'FL, 3'SL, 6'SL, natural gum and polydextrose；LNnT、 3'SL, 6'SL, natural gum and polydextrose；FOS, GOS, 2'FL, LNnT, 3'SL, natural gum and polydextrose；FOS、GOS、2'FL、 3'SL, natural gum and polydextrose；FOS, GOS, LNnT, 3'SL, natural gum and polydextrose；FOS, 2'FL, LNnT, 3'SL, natural gum And polydextrose；GOS, 2'FL, LNnT, 3'SL, natural gum and polydextrose；FOS, GOS, 3'SL, natural gum and polydextrose；FOS、 2'FL, 3'SL, natural gum and polydextrose；FOS, LNnT, 3'SL, natural gum and polydextrose；GOS, 2'FL, 3'SL, natural gum and poly- Glucose；GOS, LNnT, 3'SL, natural gum and polydextrose；2'FL, LNnT, 3'SL, natural gum and polydextrose；FOS, 3'SL, tree Glue and polydextrose；GOS, 3'SL, natural gum and polydextrose；2'FL, 3'SL, natural gum and polydextrose；LNnT, 3'SL, natural gum And polydextrose；FOS, GOS, 2'FL, LNnT, 6'SL, natural gum and polydextrose；FOS, GOS, 2'FL, 6'SL, gummy and poly-Portugal Grape sugar；FOS, GOS, LNnT, 6'SL, natural gum and polydextrose；FOS, 2'FL, LNnT, 6'SL, natural gum and polydextrose；GOS、 2'FL, LNnT, 6'SL, natural gum and polydextrose；FOS, GOS, 6'SL, natural gum and polydextrose；FOS, 2'FL, 6'SL, natural gum And polydextrose；FOS, LNnT, 6'SL, natural gum and polydextrose；GOS, 2'FL, 6'SL, natural gum and polydextrose；GOS、 LNnT, 6'SL, natural gum and polydextrose；2'FL, LNnT, 6'SL, natural gum and polydextrose；FOS, 6'SL, gummy and poly-Fructus Vitis viniferae Sugar；GOS, 6'SL, natural gum and polydextrose；2'FL, 6'SL, natural gum and polydextrose；LNnT, 6'SL, natural gum and polydextrose； FOS, GOS, 2'FL, LNnT, 3'SL, 6'SL and inulin；FOS, GOS, 2'FL, 3'SL, 6'SL and inulin；FOS、GOS、LNnT、 3'SL, 6'SL and inulin；FOS, 2'FL, LNnT, 3'SL, 6'SL and inulin；GOS, 2'FL, LNnT, 3'SL, 6'SL and inulin； FOS, GOS, 3'SL, 6'SL and inulin；FOS, 2'FL, 3'SL, 6'SL and inulin；FOS, LNnT, 3'SL, 6'SL and inulin； GOS, 2'FL, 3'SL, 6'SL and inulin；GOS, LNnT, 3'SL, 6'SL and inulin；2'FL, LNnT, 3'SL, 6'SL and inulin； FOS, 3'SL, 6'SL and inulin；GOS, 3'SL, 6'SL and inulin；2'FL, 3'SL, 6'SL and inulin；LNnT, 3'SL, 6'SL and Inulin；FOS, GOS, 2'FL, LNnT, 3'SL and inulin；FOS, GOS, 2'FL, 3'SL and inulin；FOS, GOS, LNnT, 3'SL and Inulin；FOS, 2'FL, LNnT, 3'SL and inulin；GOS, 2'FL, LNnT, 3'SL and inulin；FOS, GOS, 3'SL and inulin； FOS, 2'FL, 3'SL and inulin；FOS, LNnT, 3'SL and inulin；GOS, 2'FL, 3'SL and inulin；GOS, LNnT, 3'SL and chrysanthemum Powder；2'FL, LNnT, 3'SL and inulin；FOS, 3'SL and inulin；GOS, 3'SL and inulin；2'FL, 3'SL and inulin；LNnT、3' SL and inulin；FOS, GOS, 2'FL, LNnT, 6'SL and inulin；FOS, GOS, 2'FL, 6'SL and inulin；FOS、GOS、LNnT、6' SL and inulin；FOS, 2'FL, LNnT, 6'SL and inulin；GOS, 2'FL, LNnT, 6'SL and inulin；FOS, GOS, 6'SL and chrysanthemum Powder；FOS, 2'FL, 6'SL and inulin；FOS, LNnT, 6'SL and inulin；GOS, 2'FL, 6'SL and inulin；GOS、LNnT、6'SL And inulin；2'FL, LNnT, 6'SL and inulin；FOS, 6'SL and inulin；GOS, 6'SL and inulin；FOS、GOS、2'FL、LNnT、 3'SL, 6'SL and polydextrose；FOS, GOS, 2'FL, 3'SL, 6'SL and polydextrose；FOS, GOS, LNnT, 3'SL, 6'SL and Polydextrose；FOS, 2'FL, LNnT, 3'SL, 6'SL and polydextrose；GOS, 2'FL, LNnT, 3'SL, 6'SL and polydextrose； FOS, GOS, 3'SL, 6'SL and polydextrose；FOS, 2'FL, 3'SL, 6'SL and polydextrose；FOS, LNnT, 3'SL, 6'SL and Polydextrose；GOS, 2'FL, 3'SL, 6'SL and polydextrose；GOS, LNnT, 3'SL, 6'SL and polydextrose；2'FL、LNnT、 3'SL, 6'SL and polydextrose；FOS, 3'SL, 6'SL and polydextrose；GOS, 3'SL, 6'SL and polydextrose；2'FL、3' SL, 6'SL and polydextrose；LNnT, 3'SL, 6'SL and polydextrose；FOS, GOS, 2'FL, LNnT, 3'SL and polydextrose； FOS, GOS, 2'FL, 3'SL and polydextrose；FOS, GOS, LNnT, 3'SL and polydextrose；FOS, 2'FL, LNnT, 3'SL and Polydextrose；GOS, 2'FL, LNnT, 3'SL and polydextrose；FOS, GOS, 3'SL and polydextrose；FOS, 2'FL, 3'SL and Polydextrose；FOS, LNnT, 3'SL and polydextrose；GOS, 2'FL, 3'SL and polydextrose；GOS, LNnT, 3'SL and poly-Portugal Grape sugar；2'FL, LNnT, 3'SL and polydextrose；FOS, 3'SL and polydextrose；GOS, 3'SL and polydextrose；2'FL、3'SL And polydextrose；LNnT, 3'SL and polydextrose；FOS, GOS, 2'FL, LNnT, 6'SL and polydextrose；FOS、GOS、2'FL、 6'SL and polydextrose；FOS, GOS, LNnT, 6'SL and polydextrose；FOS, 2'FL, LNnT, 6'SL and polydextrose；GOS、 2'FL, LNnT, 6'SL and polydextrose；FOS, GOS, 6'SL and polydextrose；FOS, 2'FL, 6'SL and polydextrose；FOS、 LNnT, 6'SL and polydextrose；GOS, 2'FL, 6'SL and polydextrose；GOS, LNnT, 6'SL and polydextrose；2'FL、 LNnT, 6'SL and polydextrose；FOS, 6'SL and polydextrose；GOS, 6'SL and polydextrose；2'FL, 6'SL and poly-Fructus Vitis viniferae Sugar；LNnT, 6'SL and polydextrose；FOS, GOS, 2'FL, LNnT, 3'SL, 6'SL and natural gum；FOS、GOS、2'FL、3'SL、6' SL and natural gum；FOS, GOS, LNnT, 3'SL, 6'SL and natural gum；FOS, 2'FL, LNnT, 3'SL, 6'SL and natural gum；GOS、2'FL、 LNnT, 3'SL, 6'SL and natural gum；FOS, GOS, 3'SL, 6'SL and natural gum；FOS, 2'FL, 3'SL, 6'SL and natural gum；FOS、 LNnT, 3'SL, 6'SL and natural gum；GOS, 2'FL, 3'SL, 6'SL and natural gum；GOS, LNnT, 3'SL, 6'SL and natural gum；2'FL、 LNnT, 3'SL, 6'SL and natural gum；FOS, 3'SL, 6'SL and natural gum；GOS, 3'SL, 6'SL and natural gum；2'FL, 3'SL, 6'SL and Natural gum；LNnT, 3'SL, 6'SL and natural gum；FOS, GOS, 2'FL, LNnT, 3'SL and natural gum；FOS, GOS, 2'FL, 3'SL and tree Glue；FOS, GOS, LNnT, 3'SL and natural gum；FOS, 2'FL, LNnT, 3'SL and natural gum；GOS, 2'FL, LNnT, 3'SL and natural gum； FOS, GOS, 3'SL and natural gum；FOS, 2'FL, 3'SL and natural gum；FOS, LNnT, 3'SL and natural gum；GOS, 2'FL, 3'SL and tree Glue；GOS, LNnT, 3'SL and natural gum；2'FL, LNnT, 3'SL and natural gum；FOS, 3'SL and natural gum；GOS, 3'SL and natural gum；2' FL, 3'SL and natural gum；LNnT, 3'SL and natural gum；FOS, GOS, 2'FL, LNnT, 6'SL and natural gum；FOS、GOS、2'FL、6'SL And natural gum；FOS, GOS, LNnT, 6'SL and natural gum；FOS, 2'FL, LNnT, 6'SL and natural gum；GOS, 2'FL, LNnT, 6'SL and Natural gum；FOS, GOS, 6'SL and natural gum；FOS, 2'FL, 6'SL and natural gum；FOS, LNnT, 6'SL and natural gum；GOS、2'FL、6'SL And natural gum；GOS, LNnT, 6'SL and natural gum；2'FL, LNnT, 6'SL and natural gum；FOS, 6'SL and natural gum；GOS, 6'SL and tree Glue；2'FL, 6'SL and natural gum；And LNnT, 6'SL and natural gum.
Probiotic bacteria
(with other oligosaccharide probiotics the most above-mentioned) in addition to HMO, the nutritional composition of the disclosure can also wrap Containing one or more probiotic bacteria.In some embodiments, nutritional composition includes the combination form of HMO and probiotic bacteria so that Said composition provides synergistic benefits for end user in terms of promoting microflora growth in baby's gastrointestinal tract.
Think that probiotic bacteria is the viable microbial healthy to HOST ORGANISMS.Lactic acid bacteria (LAB) and bacillus bifidus are most common The microorganism as probiotic bacteria of type.Probiotic bacteria keeps the microbial ecological of intestinal tube, and shows physiology, immunomodulating and antibacterial Effect, thus, it is found that use probiotic bacteria can prevent and treat gastrointestinal disease and/or obstacle, the diarrhoea of pathogen-inducible and generation The antibacterial of toxin, urogenical infection and atopic diseases.
In order to make microorganism show useful internal probiotic effect, organism should be survived the most for a long time. It is important, therefore, that selection probiotics strain so that it is there are the product preventing them from quickly eliminating due to intestinal contraction effect Matter.Effectively probiotics strain can be survived under conditions of stomach, and migrates on intestinal epithelial tissue by adhering to (colonize) in intestinal, the most temporarily migrate.
The non-limitative example of the probiotics strain in this paper nutritional composition includes following kind: lactobacillus (Lactobacillus), including, bacillus acidophilus (L. acidophilus), food starch milk bacillus (L.amylovorus), short Lactobacillus (L. brevis), Lactobacillus bulgaricus (L. bulgaricus), lactobacillus casei (L. casei spp. casei), lactobacillus (L. casei spp.rhamnosus), Lactobacillus crispatus (L. crispatus),L.delbrueckii ssp.lactis, Lactobacillus fermenti (L. fermentum), lactobacillus helveticus (L. helveticus), Lactobacillus johnsonii (L.johnsonii), Lactobacillus paracasei (L. paracasei), Lactobacillus pentosus (L. pentosus), Lactobacillus plantarum (L. plantarum), Lactobacillus reuteri (L.reuteri) and Lactobacillus saki (L.sake)；Bifidobacterium (Bifidobacterium), including: animal bifidobacteria (B.animalis), bifidobacterium bifidum (B.bifidum), short double Discrimination bacillus (B.breve), bifidobacterium infantis (B.infantis) and bifidobacterium longum (B.longum)；Mycosphaerella (Pediococcus), including: pediococcus acidilactici (P.acidilactici)；Propionibacterium (Propionibacterium), Including: propionibacterium acide-propionici (P. acidipropionici), propionibacterium freudenreichii (P.freudenreichii), Zhan Shi propanoic acid Bacillus (P. jensenii)With Te Shi propionibacterium (P.theonii)；With Streptococcus (Streptococcus), including: breast Fat streptococcus (S. cremoris), Streptococcus lactis (Lister) Lohnis 1909.554. (S.lactis) and streptococcus thermophilus (S.thermophilus).Particularly preferably Probiotic bacteria include: the probiotic bacteria in human infant source, such as bifidobacterium infantis (B.infantis) M-63, bifidobacterium infantis (B.infantis) ATCC 15697, bifidobacterium infantis (B.infantis) 35624, bifidobacterium infantis (B.infantis) CHCC2228, bifidobacterium infantis (B.infantis) BB-02, bifidobacterium infantis (B.infantis) DSM20088 and baby Bifidus bacillus (B.infantis)R-0033。
Probiotic bacteria is present in nutritional composition, and total quantity is at least about 103CFU/g, including about 103 CFU/g To about 1012CFU/g, including about 106CFU/g to about 107 CFU/g。
In some embodiments, nutritional composition includes that probiotic bacteria and the first oligosaccharide (include oligofructose (fructooligosaccharide) and/or oligomeric galactose) combination form, (include at least with the second oligosaccharide further A kind of HMO, such as 2'FL, 3'FL, 3'SL, 6'SL and/or LNnT) combination.In these embodiments, the first oligosaccharide and Two oligosaccharide are present in compositions, the first oligosaccharide: the weight ratio of the second oligosaccharide is of about 10:1, or the most about 11:1 To about 8:1.
Flood tide nutrient (Macronutrients)
The nutritional composition including HMO can be prepared so that it is include in albumen, fat and carbohydrate At least one.In many embodiments, nutritional composition includes HMO and albumen, carbohydrate and fat.
Although fat, albumen and the total concentration of carbohydrate or quantity can be according to product type (that is, human milk enhancings Agent, preterm formula, infant formula, baby formulas, child's formula, subsequent segment (follow-on) formula, adult nutrient product, etc. Deng), product form (that is, auxotype solid, powder, immediately drinkable liquid or concentrated liquid) and the target diet of target user Need and change, but this concentration or quantity most typically ground fall within the scope of following embodying, including described herein Other main fat any, albumen and/or carbohydrate ingredient.
For premature labor and the liquid formulations of term infant, carbohydrate concentration (includes HMO and other carbon hydrate any Thing/oligomeric both sugar source) most typically ground is in premature labor or the scope of about 5% to about 40% of term infant formulation weight, including big About 7% to about 30%, including about 10% to about 25%；Big in premature labor or term infant formulation weight of fatty consistency most typically ground The scope of about 1% to about 30%, including about 2% to about 15%, and includes about 3% to about 10%；Protein concentration allusion quotation Type ground is in premature labor or the scope of about 0.5% to about 30% of term infant formulation weight, including about 1% to about 15%, and Including about 2% to about 10%.
For liquid human milk reinforcing agent, carbohydrate concentration (includes HMO and other carbohydrate/oligosaccharide any Both sources) most typically ground is in the scope of about 10% to about 75% of human milk reinforcing agent weight, including about 10% to about 50%, Including about 20% to about 40%；Fatty consistency most typically ground is at the model of about 10% to about 40% of human milk reinforcing agent weight Enclose, including about 15% to about 37%, also include from about 18% to about 30%；Protein concentration most typically ground is at human milk reinforcing agent The scope of about 5% to about 40% of weight, including about 10% to about 30%, also includes about 15% to about 25%.
For adult nutrient type liquid, carbohydrate concentration (includes HMO and other carbohydrate/oligosaccharide any Both sources) most typically ground is in the scope of about 5% to about 40% of adult nutrient type liquid weight, including about 7% to about 30%, including about 10% to about 25%；Fatty consistency most typically ground at adult nutrient type liquid weight about 2% to about The scope of 30%, including about 3% to about 15%, also includes about 5% to about 10%；Protein concentration most typically ground is in adult battalion Support the scope of about 0.5% to about 30% of type liquid weight, including about 1% to about 15%, also include about 2% to about 10%。
In addition, or in replacement scheme, the carbon hydrate in any liquid nutritional type compositions described herein The quantity of thing, fat and/or albumen, it is also possible to characterize with the total caloric percentage ratio of liquid nutritional type compositions is as follows Listed by table.In any thermal range (embodiment A-F) described by following table, prepare to most typically the liquid of the disclosure These flood tide nutrients (plus term " about " before each numerical value) of nutritional composition.
In a specific embodiment, liquid infant formula (drinking immediately and concentrated liquid) includes those embodiment party following Case: wherein protein component can comprise formula heat content (caloric content) about 7.5% to about 25%；Carbon water Compound component can comprise (including HMO and other carbohydrate any/oligomeric sugar source) total heat content of infant formula About the 35% of (caloric content) is to about 50%；Fatty ingredient can comprise total heat content of infant formula About the 30% of (caloric content) is to about 60%.These scopes provide as just example, and they are the most restricted. Following table indicates other suitable scope (plus term " about " before each numerical value).
When premature labor or the term infant formula that nutritional composition is powder, the existence quantity of protein component is this premature labor Or about the 5% of term infant formulation weight is to about 35%, including about 8% to about 12%, including about 10% to about 12%；Fat The existence quantity of fat component is about the 10% to about 35% of this premature labor or term infant formulation weight, including about 25% to about 30%, including about 26% to about 28%；Carbohydrate ingredient (includes HMO and other carbohydrate any/oligomeric sugar source Both) existence quantity is this premature labor or term infant formulation weight about 30% to about 85%, including about 45% to about 60%, including about 50% to about 55%.
For powder human milk reinforcing agent, the existence quantity of protein component be human milk reinforcing agent weight about 1% to about 55%, including about 10% to about 50%, including about 10% to about 30%；The existence quantity of fatty ingredient is human milk reinforcing agent About the 1% of weight is to about 30%, including about 1% to about 25%, including about 1% to about 20%；Carbohydrate ingredient Existence quantity is human milk reinforcing agent weight about the 15% of (including HMO and other carbohydrate any/oligomeric sugar source) To about 75%, including about 15% to about 60%, including about 20% to about 50%.
For powder adult nutrient product, the existence quantity of protein component be adult nutrient product weight about 10% to about 90%, including about 30% to about 80%, including about 40% to about 75%；The existence quantity of fatty ingredient is adult nutrient product About the 0.5% of weight is to about 20%, including about 1% to about 10%, including about 2% to about 5%；Carbohydrate ingredient Existence quantity is adult nutrient product weight about the 5% of (including HMO and other carbohydrate any/oligomeric sugar source) To about 40%, including about 7% to about 30%, including about 10% to about 25%.
In the Powdered nutritional type compositions of the disclosure, fat, carbohydrate and the total amount of albumen or concentration are permissible Need according to selected compositions and the diet of target user or medical science and change significantly.Flood tide nutrition is listed below Other suitable embodiment of element concentration.In this respect, total amount or concentration refer to all fat in powder composition, carbon aquation Compound and protein source.For Powdered nutritional type compositions, most typically ground and preferably described by following table any specifically This total amount of latitude of formulation or concentration (plus term " about " before each numerical value).
Fat
The nutritional composition of the disclosure can optionally comprise any fat source.Suitable fat source bag used herein Include: be suitable for that oral nutrient type compositions uses and this main component of compositions and any fat of feature compatibility or fat Fat source.Such as, in a specific embodiment, adipose-derived in long-chain polyunsaturated fatty acid (LCPUFA).
Include for the exemplary LCPUFA of nutritional composition, such as, ω-3 LCPUFA and ω-6 LCPUFA.Tool The LCPUFA of body includes: derived from 22 carbon six of oil sources (such as vegetable oil, halomereid oil, fungal oil and fish oil) Olefin(e) acid (DHA), eicosapentaenoic acid (EPA), clupanodonic acid (DPA), arachidonic acid (ARA), linoleic acid, linolenic acid (alpha linolenic acid) and gamma-Linolenic acid.In a specific embodiment, LCPUFA stems from fish oil, such as, and catfish (menhaden), salmon, long tail anchovy, morrhua, flatfish, tuna or herring oil.Together with HMO in nutritional composition Especially preferred LCPUFA include DHA, ARA, EPA, DPA and its combination form.
In order to make the potential side effect of high dose LCPUFA in nutritional composition reduce, it is preferable that at nutritional composition In, the content of LCPUFA is less than 3% weight of total lipid content, including 2% weight less than total lipid content, including less than total 1% weight of fat content.
Can with free fatty acid form, triglyceride form, triglyceride form, monoglyceride form, phospholipid form, Esterified form or above-mentioned one or more form of mixtures provide LCPUFA, preferably glycerine three ester-formin.Specifically real at another Executing in scheme, fat stems from short-chain fatty acid.
Suitably fat or other limiting examples bag of fat source for nutritional composition described herein Include: Oleum Cocois, fractionated coconut oil, soybean oil, Semen Maydis oil, olive oil, safflower oil, high oleic safflower oil, oleic acid (EMERSOL 6313 oleic acid, Cognis Oleochemicals, Malaysia), miglyol 812 (medium chain triglyceride), Oleum helianthi, high gas oil ratio to Day certain herbaceous plants with big flowers oil, Petiolus Trachycarpi and palm kernel oil, palm olein, Canola oil, marine product oil, fish oil, fungal oil, algal oil, Oleum Gossypii semen and its Combination.
Albumen
The nutritional composition of the disclosure can also comprise albumen the most further.It is suitable for oral nutrient type compositions And with the main component of this compositions and any protein sources of feature compatibility, it is suitable in nutritional composition using.
Include for the suitable albumen of nutritional composition or the limiting examples of protein sources: hydrolysis, partial hydrolysis Or the albumen of non-hydrolytic or protein sources, it can obtain by any of or other suitable source, such as milk (such as, cheese egg In vain, milk surum), animal (such as, meat, fish), frumentum (such as, Oryza glutinosa, Semen Maydis), plant (such as, Semen sojae atricolor) or a combination thereof.This hatching egg White limiting examples includes: lactoprotein separator, lactoprotein concentrate described herein, casein separator, thoroughly The casein of hydrolysis, lactalbumin, casein sidium or calcium caseinate, full Lac Bovis seu Bubali, the partially or completely milk of defat, soybean protein divides From thing, soybean protein concentrate, etc..In a specific embodiment, nutritional composition include derived from the mankind and/or The protein sources of the milk protein of cattle.
In one embodiment, protein sources is the protolysate of hydrolysis.About this point, term " hydrolyzed protein " or " protolysate " can intercourse use in this article, and includes the albumen thoroughly hydrolyzed, and wherein degree of hydrolysis most typically be At least about 20%, including about 20% to about 80%, also include about 30% to about 80%, the most about 40% to About 60%.Degree of hydrolysis is the degree being made peptide bond fission by method for hydrolysis.Formulation art those of ordinary skill, by quantitative institute Select amino nitrogen and the ratio (AN/TN) of total nitrogen of the protein component of liquid preparation, can be easily determined by as characterizing these real Execute the protein hydrolysis degree of the thorough hydrolyzed protein component purpose of scheme.The USP titrimetry measuring amino nitrogen content is utilized to come quantitatively Amino nitrogen component, and total nitrogen component is measured by Tecator Kjeldahl method, these methods are that analytical chemistry field is general Known to logical technical staff.
Suitably hydrolyzed protein may include that soybean protein hydrolyate, casein protein hydrolysate, hydrolyzed whey protein Thing, rice protein hydrolysate, Rhizoma Solani tuber osi protein hydrolysate, fish protein hydrolyzate, egg white protein hydrolysates, hydrolytic collagen (gelatin protein hydrolysate), the compositions of animal and plant protolysate, and a combination thereof.Particularly preferably Protolysate include the sodium caseinate of lactalbumin hydrolysate and hydrolysis.
When using protein sources in nutritional composition, protein sources can include at least about 20% (by total protein by weight Calculate) protolysate, including about 30% to 100% (calculating by total protein by weight) protolysate, including about 40% to greatly About 80% (calculating by total protein by weight) protolysate, including about 50% (calculating by total protein by weight) protolysate.? In one specific embodiments, nutritional composition includes 100% (calculating by total protein by weight) protolysate.
Carbohydrate
The nutritional composition of the disclosure can the most optionally comprise any carbohydrate, and this carbohydrate is fitted Share in oral nutrient type compositions, and with the main component of this compositions and feature compatibility.
Permissible for the suitable carbohydrates of nutritional composition described herein or the limiting examples in its source Including: maltodextrin, hydrolysis or modified starch or corn starch, glucose polymer, corn syrup, corn syrup solids, The carbohydrate obtained by Oryza glutinosa, the carbohydrate obtained from Semen Pisi sativi, the carbohydrate obtained from Rhizoma Solani tuber osi, Maninot esculenta crantz., Sucrose, glucose, fructose, lactose, high-fructose corn syrup, Mel, sugar alcohol (such as, maltose alcohol, erithritol, sorbose Alcohol), and artificial sweetening (such as, sucralose (sucralose), acesulfame potassium (acesulfame Potassium), Stevia rebaudiana) and a combination thereof.Particularly desirable carbohydrate is the Fructus Hordei Germinatus magma of low DE (DE) Essence.
Other optional component
The nutritional composition of the disclosure can comprise other optional component further, and this component can regulate this group The physics of compound, chemistry, aesthetic property or processing characteristics, or when using in target group, medicine or other battalion can be played Support the effect of component.Many this optional components are known components, or are additionally suitable for medical food or other nutrition Type product or pharmaceutical dosage form, and also can use in compositions herein, condition is, is orally administered to this optional component It is safe, and compatible with the key component in selected product form and other component.
The limiting examples of this optional components includes: preservative, emulsifying agent, buffer agent, pharmaceutical active thing, antiinflammatory Agent, other nutrient described herein, coloring agent, flavoring agent, thickening agent and stabilizer, emulsifying agent, lubricant, etc..
This nutritional composition can comprise sweeting agent further, preferably includes at least one sugar alcohol, such as maltose alcohol, Erithritol, Sorbitol, xylitol, mannitol, hydroxyl isomaltulose (isolmalt) and lactose, and preferably include to Few a kind of artificial or dynamical sweeting agent, such as acesulfame K (acesulfame K), aspartame, sucralose, Saccharin, Stevia rebaudiana and Tagatose.The combination of these sweeting agents, especially sugar alcohol and artificial sweetening agent, it is especially useful in preparation has conjunction The liquid beverage embodiment of the disclosure of the advantageous feature needed.These combinations of sweeteners are shielding unwelcome taste Aspect is particularly effective, and this taste is sometimes relevant with interpolation vegetable protein in liquid beverage.In this nutritional composition, optionally Sugar alcohol concentration can be in the scope of at least the 0.01% of this nutritional composition weight, including 0.1% to about 10%, and bag Include about 1% to about 6%.Optional artificial sweeteners's agent concentration can be at the model of about the 0.01% of this nutritional composition weight Enclose, including about 0.05% to about 5%, also include about 0.1% to about 1.0%.
Flowable or anti-caking agent can be included in nutritional composition described herein, thus postpone powder along with The passage of time and produce condensation or caking, and powder embodiment is easily flowed out from its container.Known or applicable Being suitable for using herein for auxotype powder or any of flowable of product form or anti-caking agent, it is non-limiting Example includes: tricalcium phosphate, silicate and a combination thereof.In this nutritional composition, the concentration root of flowable or anti-caking agent Change according to product form, other component selected, object mobility etc., but most typically ground is in this nutritional composition weight The scope of about 0.1% to about 4%, including about 0.5% to about 2%.
Stabilizer can also be included in this nutritional composition.Known or be suitable for nutritional composition any surely Determining agent to be also suitable for using herein, some of limiting examples includes: natural gum, such as xanthan gum.Stabilizer can be this battalion Support about the 0.1% to about 5.0% of type composition weight, including about 0.5% to about 3%, including about 0.7% to about 1.5%。
It addition, this nutritional composition can comprise one or more antioxidant, thus provide nutritional support, and reduce Oxidative stress (oxidative stress).In the nutritional composition of the disclosure, can include being suitable for being orally administered to Any antioxidant, including, such as, vitamin A, vitamin E, vitamin C, retinol, tocopherol and carotenoid.
In a specific embodiment, the antioxidant in nutritional composition includes carotenoid, such as, Phylloxanthin, zeaxanthin, lycopene, beta-carotene and a combination thereof thing, especially carotenoid phylloxanthin, lycopene and The compositions of beta-carotene.Nutritional composition containing these combination forms the most selected and defined can be used for adjusting Save premature labor and the inflammation of term infant and/or the level of C reactive protein.
This nutritional composition can comprise other vitamin various or related nutritional element, its limiting examples further Including: vitamin D, vitamin K, vitamin B1(thiamine), riboflavin, pyridoxol, vitamin B12, vitamin PP (niacin), folic acid, pantothenic acid, biotin, choline, inositol, its salt and derivant, and a combination thereof.
This nutritional composition can comprise any other extra mineral various, its limiting examples bag further Include: calcium, phosphorus, magnesium, ferrum, zinc, manganese, copper, sodium, potassium, molybdenum, chromium, chloride, and a combination thereof.
In order to improve the integrity of gut barrier further and/or reach maturity, the nutritional composition of the disclosure also may be used To comprise selected from following nucleotide and/or nucleotide precursor thing: nucleoside, purine base, pyrimidine base, ribose and deoxyribose.Core Thuja acid can be a phosphoric acid (phosphate), diphosphonic acid (phosphate) or triphosphoric acid (phosphate) form.Nucleotide can To be ribonucleotide or deoxyribonucleotide.Nucleotide can be monomer, dimer or polymer (including RNA and DNA). Nucleotide can be present in nutritional composition with free acid or salt form, preferably one sodium salt.
Suitable nucleotide in nutritional composition include following in one or more: cytidine 5'-mono-phosphoric acid, urine Glycosides 5'-mono-phosphoric acid, adenosine 5'-mono-phosphoric acid, guanosine 5'-1-mono-phosphoric acid and/or inosine 5'-mono-phosphoric acid, more preferably cytidine 5'-mono-phosphorus Acid, uridnine 5'-mono-phosphoric acid, adenosine 5'-mono-phosphoric acid, guanosine 5' mono-phosphoric acid and inosine 5'-mono-phosphoric acid.
Preparation method
Effectively can make with the solid product selected by any of technology of preparing or preparation or other of liquid form Standby technology, the nutritional composition of the preparation disclosure.For any given product form, such as nutritional liquid or powder End, many this technology are known, and those of ordinary skill in the art can be readily applied to battalion described herein Support type compositions.
Therefore, it can with any various known or other effectively preparation or preparation method, nutrition of the preparation disclosure Type compositions.In a suitable preparation method, such as, the serosity of preparation at least three independence, including albumen in fat (PIF) serosity, carbohydrate-mineral (CHO-MIN) serosity and albumen (PIW) serosity in water.The following PIF that formed starches Liquid: by oil (such as, Canola oil, Semen Maydis oil, etc.) heat and mix, then add emulsifying agent (such as, lecithin), liposoluble A part for property vitamin and total protein (such as, cmps, etc.), continuous heating and stirring.Form CHO-MIN as follows Serosity: under heated and stirred, by mineral (such as, potassium citrate, dipotassium hydrogen phosphate, sodium citrate, etc.), trace and super trace Amount mineral (TM/UTM premix), thickening or suspending agent (such as, Avicel (avicel), gellan (, Gellan), carrageenan) it is added to the water.The CHO-MIN serosity obtained is kept 10 minutes, continuous heating and stirring simultaneously, and The extra mineral of rear addition (such as, potassium chloride, magnesium carbonate, potassium iodide, etc.) and/or carbohydrate (such as, HMO is low Polyfructose. (fructooligosaccharide), sucrose, corn syrup, etc.).Then, under heating and stirring, will residue Albumen (if any) mixing, formed PIW serosity.
Then, under heated and stirred, the serosity obtained is mixed, and pH value is regulated to 6.6-7.0, the most right Said composition carries out short time high temperature (HTST) and processes, and during this period, said composition is heat-treated, emulsifying and homogenizing, then cools down. Add water soluble vitamins and ascorbic acid, if necessary, by pH value regulation to target zone, add flavoring agent, add Water, it is thus achieved that target total solid level.Then, aseptic packaging said composition, form the auxotype emulsion of aseptic packaging.Then, may be used So that this emulsion is diluted further, heat treatment and packaging, form the liquid drunk immediately or concentrate, maybe it can be carried out at heat Reason, with post-treatment and be packaged into the powder that can prepare again, such as, spray-dried powders, dry mixing mixed-powder, the powder of reunion.
Auxotype solid, such as, the auxotype powder of spray drying or the auxotype powder of dry mixing mixing, it is possible to use suitable Together in preparation and preparation auxotype powder known collection or other effective technology prepare.
Such as, when auxotype powder is the auxotype powder being spray-dried, spray drying step can also include known Or be suitable for preparing any spray drying technology of auxotype powder.Spray drying method and technology that known many is different can For field of nutrition, they are suitable for preparation spray dried nutritional type powder herein.
A kind of method preparing spray dried nutritional type powder includes: formed containing the fatty and optional albumen of predigestion, Carbohydrate and the aqueous slurry of other fat source or liquid, and by its homogenizing, then this serosity or liquid spray are dried, system The standby auxotype powder being spray-dried.The method may further include the following step: (other nutrition composition is included institute herein Describe one or more component any) be spray-dried, dry mixing be mixed or added to be spray-dried auxotype powder in.
Prepare other suitable method of nutritional composition, such as, be described in United States Patent (USP) 6,365,218 (Borschel et al.), United States Patent (USP) 6,589,576 (Borschel et al.), United States Patent (USP) 6,306,908 (Carlson et al.) With in U.S. Patent application 20030118703 A1 (Nguyen et al.), in the most consistent degree, its description is being combined To herein by reference as.
Using method
Nutritional composition described herein can be used for tackling one or more disease, obstacle or disease discussed herein, Or can be used for providing one or more benefit described herein for premature infant, baby, child, child and adult's (including anemia of pregnant woman) Place.Use the premature infant of nutritional composition described herein, baby, child, child, adult and anemia of pregnant woman, can actually suffer from The disease being described or disease, or bothered by it, or easily suffer from this disease or disease or be in and suffer from this disease or disease Danger among (it is to say, actually may not suffer from disease or disease, but compared with population, owing to some is sick Disease, family history etc., be among the high-risk suffering from this disease or disease).No matter premature infant, baby, child, child, one-tenth People and anemia of pregnant woman the most actually suffer among this disease or disease or the danger being in this disease or disease or easily suffer from this Disease or disease, classify as premature infant, baby, child, child, adult and anemia of pregnant woman " needs " herein and help tackle and resist this Disease or the crowd of disease.Such as, premature infant, baby, child, child, adult and anemia of pregnant woman may actually suffer from breathing inflammation, Or be likely to be at due to family history or other medical condition and to suffer among the danger breathing inflammation (easily suffering from breathing inflammation). No matter premature infant, baby, child, child, adult and anemia of pregnant woman the most actually suffer from this disease or disease or are only in this disease Among the sick or danger of disease or easily suffer from this disease or disease, help early with nutritional composition described herein Newborn baby, baby, child, child, adult and anemia of pregnant woman are within the scope of the present disclosure.
Based on foregoing teachings, because the certain methods embodiment of the disclosure relates to concrete lower hyte or the Asia determining individuality Group is (it is to say, " needs " helps to solve one or more disease specific noted herein or the individual lower hyte of concrete disease Or subgroup), so, for some disease or disease, not all premature infant, baby, child, child, Cheng Renhe Anemia of pregnant woman all fall the lower hyte of premature infant described herein, baby, child, child, adult and anemia of pregnant woman or subgroup scope it In.
Nutritional composition described herein comprise single HMO or with one or more other component associated with HMO, carry For can at least improve the nutrient source of intestinal/intestinal tube function.Specifically, this nutritional composition can stimulate the gastrointestinal tract of individuality In enteric nervous cell, thus improve intestinal/intestinal tube barrier integrity；Improve and feed toleration (such as, minimizing diarrhoea, loose stool, gas Body and abdominal distention)；Reduce the angor (colic) of baby；Prevent necrotizing enterocolitis and other obstacle of premature infant；To paying Gastrointestinal disease that enteric nervous system is relevant and obstacle；Tackle intestinal contraction and the gastrointestinal disease of inflammation and obstacle；Correction intestinal tube is raw The effect of state imbalance；Affect the long-term regulation of allergy toleration.
More particularly, in some embodiments, can suffer from, easily suffer from relevant to enteric nervous system and/or The gastrointestinal disease relevant to intestinal contraction and inflammation and obstacle or be in the individuality among the danger of this gastrointestinal disease and obstacle This nutritional composition, this gastrointestinal disease and obstacle can include, such as, irritable bowel syndrome, colitis is (such as, downright bad Property enterocolitis, Crohn disease, ischemic colitis, hidden pityrosporion ovale enterocolitis, pseudomembranous colitis, giant cell is sick Poison, ulcerative colitis), food intolerance and food allergy.
As it has been described above, along with the g and D degree of individual immunity system improves, the nutritional composition of the disclosure also may be used To play, enhancing is individual to be resisted microorganism infection and promotes that beneficial microbe clump is at the gastrointestinal tract of baby, child, child or adult The effect of middle growth.
Further, when HMO Yu LCPUFA and/or antioxidant are combined, being especially combined with carotenoid, HMO can To reduce oxidative stress, this oxidative stress is metabolic disorder, in this disease, and biomolecule (such as, the lipid mistake of oxidation Oxide and their catabolite, protein carbonyl and the DNA of oxidative damage) generation and accumulation increase.The knot of oxidative stress The scope of fruit is: from harmful change of metabolic mechanism to inflammation and cell and tissue die.Correspondingly, by reducing the nothing of baby The inflammation limited and the incidence rate of oxidation, reduce the destruction to tissue inwall, reduces cell death, reduces inflammatory disease further Disease, such as, the sickness rate of necrotizing enterocolitis (NEC).
It addition, the nutritional composition of the disclosure can be also used for improving individual cognitive competence, the most easily suffer from The individuality of neurodegenerative disease or be in the individuality among neurodegenerative disease danger, neurodegenerative disease can include, such as, Alzheimer's disease, Heng Tingdunshi chorea, Parkinson's disease and schizophrenia, or it is caused to suffer from cognitive development weakening Disease or the individuality of neuronal development disease, for example it is to be noted that the how dynamic obstacle of defect and autism.
Embodiment
The following example illustrates the nutritional composition of the disclosure and the specific embodiments of method and/or spy Levy.These embodiments purpose just to illustrating is provided, should not be considered to restriction of this disclosure, do not carrying on the back Under conditions of the spirit and scope of the disclosure, it can be carried out many changes.The quantity of all illustrations is based on group The percetage by weight of the gross weight of compound, unless otherwise mentioned.
The compositions illustrated is to store stable auxotype combination according to prepared by preparation method described herein Thing, therefore, unless otherwise noted, the compositions of each illustration includes embodiment and the steaming and decocting bag of sterile-processed The embodiment of dress.
Nutritional liquid embodiment is oil-in-water type water-based emulsion, is packaged in 240 ml plastic containers, compositions/ After packaging, store at a temperature of 1-25 DEG C, the physical stability of 12-18 month can be kept.
Embodiment 1-5
Embodiment 1-5 illustrates the auxotype emulsion that can drink immediately of the disclosure, and component therein is listed in the table below In.Kilogram to list the quantity of all components, according to every batch of product 1000 kilograms calculating, unless otherwise mentioned.
Embodiment 6-10
Embodiment 6-10 illustrates the auxotype emulsion that can drink immediately of the disclosure, and component therein is listed in the table below In.Kilogram to list the quantity of all components, according to every batch of product 1000 kilograms calculating, unless otherwise mentioned.
Embodiment 11-15
Embodiment 11-15 illustrates the concentrated liquid emulsion of the disclosure, and component therein is listed in the following table.With kilogram List the quantity of all components, according to every batch of product 1000 kilograms calculating, unless otherwise mentioned.
Embodiment 16-20
Embodiment 16-20 illustrates the auxotype powder of the spray drying of the disclosure, and component therein is listed in the table below In.Kilogram to list the quantity of all components, according to every batch of product 1000 kilograms calculating, unless otherwise mentioned.
Embodiment 21-25
Embodiment 21-25 illustrates the auxotype powder of the spray drying of the disclosure, and component therein is listed in the table below In.Kilogram to list the quantity of all components, according to every batch of product 1000 kilograms calculating, unless otherwise mentioned.
Embodiment 26-30
Embodiment 26-30 illustrates the auxotype emulsion that can drink immediately of the disclosure, and component therein is listed in down In table.Kilogram to list the quantity of all components, according to every batch of product 1000 kilograms calculating, unless otherwise mentioned.
Embodiment 31-34
Embodiment 31-34 illustrates the concentrated liquid human milk reinforcing agent of the disclosure, and component therein is listed in the following table. Kilogram to list the quantity of all components, according to every batch of product 1000 kilograms calculating, unless otherwise mentioned.
Embodiment 35
In this embodiment, analyze 2'-fucosyllactose (2'FL) or 3'-fucosyllactose (3'FL) is nibbled in stimulation The effect in terms of enteric nervous cell in the gastrointestinal tract of tooth class.
Specifically, using enterokinesia model (using the mouse Colon of luminal perfusion), test 2'FL or 3'FL is to intestinal god Effect of stimulation through cell.With concentration be 1 mg/ml, 2'FL or 3'FL of 0.5 mg/ml and 0.1 mg/ml irrigate colon muscle 15 minutes.Analyze frequency and the amplitude of muscle contraction.Result is shown in Figure 1.
As shown in the results, 2'FL or 3'FL directly stimulates neurocyte, with intestinal tube microflora and/or their metabolite Unrelated.Specifically, the frequency of contraction and amplitude are as one man, reduce in dose response mode.This result represents, 3'FL compares 2'FL More effectively.
Embodiment 36
In this embodiment, the fermenting speed of various stodgy carbohydrate is measured.
For selecting eight the including of babies participating in experiment/exclusion standards to include: baby's subjects born at term, gestational age 38 to 42 Week；The weight of baby is higher than 5 the percent of birth weight or above (the infant was at or above the Fifth percentile for weight at birth)；Prove baby fetus is not had undesirable effect diabetes, Pulmonary tuberculosis or the maternal medical history of perinatal infection；Vagina is born；When entering research, the age is at least 2 months, but less than the age 4 Month；There is no known heart, breathing, gastrointestinal or other systemic disease, such as urinary tract infection or otitis media；Seriously draw to being enough to Play the blood group incompatibility history of blood problems；Do not accept any medicine (except supplementary vitamin), never received antibiotic. Eight babies are allowed to use normal breast milk or infant formula.Four breast feedings for baby, four formula feedings (four for baby Plant and be purchased one of infant formula).
On the same day of experiment in vitro, collect the fecal specimens on diaper, and be ready within 15 minutes of defecation.Prepare Time, sample is placed in the container with warm water, and analyzes.At CO2Under air-flow, by mixing 15 in Waring agitator Second, fecal specimens is diluted in (1:10, wt/vol) in anaerobism dilute solution.And at CO2In atmosphere, by four layers of cheese bag Cloth filters the feces of this mixing, dilution, is sealed in 125 mL serum bottle.Inoculum is saved at 37 DEG C, until in pipe Till external inoculation.
The oligosaccharide substrate being suitable for growing antibacterial includes: oligomeric galactose (GOS) 95 (GOS；Inalco Pharmaceuticals, San Luis Obispo, California), α-(2-6')-N-acetyl-neuraminate base-lactose Sodium salt (6'SL；Inalco Pharmaceuticals, San Luis Obispo, California)；2'-α-L-pyrans rock Algae glycosyl-D-lactose (2'FL； Inalco Pharmaceuticals, San Luis Obispo, California)； LNnT； Orafti®HP inulin (HP inulin) (BENEO-Orafti, Belgium)；With arabic gum (Fisher Scientific, Pittsburgh, Pennsylvania)。
In Vitro Fermentation model
Each substrate is weighed about 80 mg, and sampling is triplicate every time, and each sample is put into 16 mL Balch pipes In, this Balch pipe is for simulating the model of big intestinal fermentation.By culture medium (table 1；An aliquot sample (7.2 mL) Fig. 2) It is transferred aseptically in Balch pipe, covers with butyl rubber bung, and seal with aluminum cap.The pipe of HP inulin and arabic gum will be comprised Preserve at 4 DEG C about 12 hours, made substrate be hydrated before starting fermentation.Before inoculation, these pipes are placed on 37 DEG C In water-bath about 30 minutes.Due to the expense of substrate be difficult at baby obtain sample, so, once obtain fecal specimens, The pipe comprising GOS, 6'SL, 2'FL and LNnT is hydrated, and puts in 37 DEG C of water-baths, until inoculation.
With feces aseptic inoculation sample and the blank tube of 0.8 ml dilution.By pipe 37 DEG C of cultivations, periodically mixing in every 2 hours Once, till 12 hours.After inoculation 0,3,6 and 12 hours, take out pipe from 37 DEG C of couveuses, and immediately treat Analyze.The pH value of inclusions in pipe is measured with standard pH meter.Collect 3 ml double sampling sample (subsample) liquid, be used for Short-chain fatty acid and lactic acid (lactate) are analyzed.Obtain 2 mL double sampling samples, and freezing at-80 DEG C, divide for antibacterial Analysis.
Short-chain fatty acid (SCFA) is analyzed
3 mL liquid (taking out from sample cell, analyze for SCFA) aliquot sample is joined 0.75 mL immediately In 25% Metaphosphoric acid.Use Hewlett-Packard 5890A Series II gas chromatograph and glass column (180 cm x 4 mm I.d., with 10% SP-1200/1% H3PO4Filling 80/100+ mesh Chromosorb WAW (Supelco Inc., Bellefonte, PA)) measure acetate, propionate and the concentration of butyrate.Oven temperature, detector temperature and syringe temperature Degree is 125,175 and 180 DEG C respectively.SCFA that SCFA concentration value produces for blank tube and the concentration of 0 hour of each substrate It is corrected for.The total SCFA of total amount form calculus with acetate, propionate and butyrate.
Use the combination process of SAS (SAS Inst., Inc., Cary, NC), set with completely random district group (block) Split plot again (split-split-plot) the methods analyst data of meter.District's group is defined as the diet (breast milk or formula) of baby. Fixing test effect includes diet, substrate and time, has also probed into interaction (if meaningful).At this model In, including baby and time, it is random effect.Use the LSD of protection, meansigma methods is distinguish between with Tukey regulation, with Control release error.Report least square meansigma methods, report the set SEM for all response criteria simultaneously.P < The probability of 0.05 regards as statistically having significance.
Result and discussion
For all substrates (except arabic gum), pH value change (from the beginning of baseline) As time goes on reduces (P < 0.0001) (Fig. 3).After inoculation 3,6 and 12 hours, for arabic gum substrate, pH value change (from the beginning of baseline) is minimum (P < 0.0001), for LNnT, 2'FL and GOS substrate, pH value change maximum.PH value reduces the mark being to ferment, and these Data reflect SCFA and produce.
3,6 and 12 hours of fermentation, in the middle of substrate, total SCFA produces different (Fig. 4) (P < 0.0001).Arabic gum Produce the SCFA of minimum number, and be As time goes on not changed in.After fermenting 3 and 6 hours, with other substrates all Compare, total SCFA lower (P < 0.05) that HP inulin produces, and compared with GOS, total SCFA that 6'SL produces lower (P < 0.05).Ferment 12 hours, relative to 2'FL, 6'SL, GOS and LNnT substrate, total the lowest (P of SCFA that HP inulin produces <0.05).Additionally, after fermentation 12 hours, compared with 2'FL, total SCFA that 6'SL and GOS substrate produces more (P < 0.05)。
Embodiment 37
In this embodiment, HMO, HMO precursor of purification and the probiotics fermention ginseng of other oligosaccharide probiotics are measured Number.
Bacterial cultures
Start to inoculate all of bifidobacterium strain with freezing storing solution, be grown in being supplemented with 0.5 g/L L-half Guang ammonia In deMan Rogosa Sharpe (MRS) gravy (Difco, Detroit, MI) of acid/HCl, and at anaerobic chamber (90% N2、5% CO2With 5% H2Cultivate 24 hours in), at 37 DEG C.Subsequently, make this culture in semisynthetic MRS culture medium (sMRS)+0.5 g/L Cys/HCl (supplements the glucose of 1% (w/v) filter-sterilized as single carbohydrate Source) on by twice.Second time, by afterwards, gets out culture, as the inoculum of growth test as described below.For All bacterial strains of this embodiment are listed in the following table.
Bacteriagrowthtest
Second time is by after sMRS+ glucose+cysteine, by culture 10 mL aseptic sMRS+ cysteine (not having carbohydrate) washed once, and is resuspended in 10 mL aseptic sMRS+ cysteine (not having carbohydrate), and It is used as 1% inoculum afterwards.Carbohydrate for this embodiment is shown in following table.Carbohydrate is used 0.22 Mm filter Device is sterilized, and uses under 1% ultimate density.In the cellular board of Bioscreen 100 hole, make cell at 250 μ L sMRS+ half Guangs Growth in propylhomoserin (covering with 50 μ L mineral oil).Bioscreen C automatic microbe growth curve is used to analyze system, 600 Nm measures absorbance (OD600), monitoring cell growth.With intermittent mode running plate reader, read with the interval times of 30 minutes Go out absorbance, and shake 30 seconds with maximal rate at first.Tester is by the culture medium of the inoculation of not carbohydrate containing Composition.Owing to the space of microtitration plate limits, carbohydrate is divided into three independent group: A plate (HMO precursors: Fructus Vitis viniferae Sugar, galactose, lactose, NAG, fucose, fructose and sialic acid), B plate (prebiotics: glucose, PurimuneTMGOS is pure PurimuneTMGOS, Vivinal GOS, pure Vivinal GOS, scFOS and PDX) and C plate (HMO: glucose, 6'- SL, 3'-SL, 2'-FL, 3'-FL and LNnT).All three plate includes that positive control (glucose) and negative control (do not have carbon water Compound).
Growth curve of bacteria
Deduct the OD600 of basal medium (sMRS)+cysteine from the sample panel of each probiotic bacteria, thus correct each The OD600 data of carbohydrate.The growth data corrected by inspection, determines maximum OD.At the beginning of the OD of maximum correction deducts Begin the OD (time point 0) corrected, and thus measures OD.Make sample grow the most in triplicate by biology, use these parallel assays Meansigma methods represent the growth kinetics data obtained.
For growth curve chart, the antibacterial that first drafting is grown in the culture medium (sMRS) of not carbohydrate containing The OD600 figure to the time.For other carbohydrates all, by deducting the OD600 of sMRS, correct OD600 data.
The purification of GOS
By PurimuneTMGOS (GTC Nutrition) and Vivinal GOS (Friesland Foods Domo) is pure Change, it is thus achieved that the GOS of purification.It is applied to the stock solution of 1.5 g/100 mL fill Sephadex's G25 medium (Sigma) In XK post (XK 50/100 post, 5.0 x 100 cm, GE healthcare).With pure this post of distilled water eluting, elution speed is 8 Ml/min, and utilize Gilson FC 203B fraction collector to collect 12 mL fractions.
Use phenolsulfuric acid is tested, and detects the carbohydrate in every 2-3 fraction.In brief, drip at 96 hole trace Determine in plate, 50 μ L sample (2 μ L fractions and 48 μ L distilled water, in hole) are joined in 150 μ l concentrated sulphuric acids rapidly.Then stand I.e. add 30 μ l 5% phenol, and by plate 80 DEG C, keep 30 minutes in static water-bath.After being cooled to room temperature 5 minutes, by it Dry, and with the absorbance at SpectraMax Plus384 spectrophotometric determination 490 nm.Based on carbohydrate analysis, The fraction comprising minimum two and monosaccharide is merged, lyophilization (freeze-drying system/Freezezone 4.5/LABCONCO), be used for Bacterial fermentation is tested.It addition, in order to obtain enough purification GOS for growth experiment, collect the lyophilization of multi-pass operation GOS (use PurimuneTMGOS carries out 5 operations, carries out 3 operations with Vivinal GOS).
Result and discussion:
GOS purification
GOS is that the glycosyl galactose that turns by lactose produces, and already functions as the prebiotics fill-in of child nutriment. Due to the problem of GOS synthesis, commodity GOS product is the mixture of many different carbohydrates, and it can include list and disaccharide. In order to test GOS's rather than be generally not capable of arriving the list of colon and the fermentation parameter of disaccharide, it is thus achieved that be substantially free of list and two The pure GOS fraction of sugar.Glucose (monosaccharide), lactose (disaccharide) and Raffinose (trisaccharide) are used as standard sample.With supplier's Information is consistent, PurimuneTM List and disaccharide that GOS contains are more less than what Vivinal GOS contained.Such as, before Raffinose peak The Purimune in faceTMGOS peak explanation PurimuneTM GOS is mainly made up of the sugar of trisaccharide or bigger.For Vivinal GOS, observes peak, for lactose at similar fraction numbering.Owing to lactose starts appearance at fraction 55, so, two supplies Commercial city uses fraction 30 to 55 as the GOS of purification.
HMO precursor ferments
The bacillus bifidus of all tests is seldom grown in basal medium (sMRS+ cysteine) (Fig. 5 A), and they The most preferably it is grown in glucose (Fig. 5 B).Generally, it is impossible to the life on lactose of the bacillus bifidus (Fig. 5 C) of ferment galactose Long also minimizing (Fig. 5 D).Do not have a kind of bacillus bifidus can ferment HMO and mucinous two key component L-fucoses (figure 5E) or sialic acid (Fig. 5 F).Only bifidobacterium breve (B.breve) ATCC 15700 can ferment NAG (Fig. 5 G), it is HMO With mucinous key component.Finally, major part bacillus bifidus can ferment fructose (Fig. 5 H).
Prebiotics ferments
From PurimuneTM GOS removes list and disaccharide, causes the growth of all bacillus bifiduss to reduce (Fig. 6 A).True On, Bifidobacterium lactis (B.lactis) DSM 10140, animal bifidobacteria (B. animalis)The double qi of ATCC 25527, two qi Bacillus (B. bifidum)ATCC 29521, Bifidobacterium lactis (B.lactis) Bf-6 and bifidobacterium longum (B.longum) can not The Purimune of fermentation purificationTMGOS (Fig. 6 D).For the Vivinal GOS of purification, it also seen that similar figure (Fig. 6 F), only But see with Vivinal GOS ratio PurimuneTMIt is more that GOS grows.In order to simulate colonic environment, need to remove The free list being present in these products and disaccharide.Again it is apparent that PurimuneTMThe relative concentration of the oligosaccharide of GOS is more High.Measured by Δ OD, two kinds of bifidobacterium infantises (B.infantis) bacterial strain on the GOS of purification all best raw elder Row, this prove, if target be to increase bifidobacterium infantis (B.infantis), GOS is incorporated into the conjunction in infant formula The prebiotics of reason.All bacillus bifiduss of test, animal bifidobacteria (B. animalis) except ATCC 25527, can Fermentation scFOS (Fig. 6 G), and do not have a kind of bacillus bifidus can ferment polydextrose (PDX) (Fig. 6 H).
HMO ferments
Only bifidobacterium infantis (B.infantis) ATCC 15697 and bifidobacterium infantis (B. infantis)M-63 Can be fermented 6'-SL, 3'-SL, 2'-FL and 3'-FL (Fig. 7 C-7F).In all cases, bifidobacterium infantis (B. infantis)M-63 than bifidobacterium infantis (B.infantis) ATCC 15697 growth more preferable.On more complicated LNnT (Fig. 7 G), bifidobacterium breve (B.breve) ATCC 15700 and two kind of bifidobacterium infantis (B.infantis) strain growth More preferably rather than bifidobacterium breve (B.breve) M16-V growth more preferable.It addition, two kinds of bifidobacterium infantises (B. infantis)Bifidobacterium infantis in the presence of the ability of strain fermentation HMO and breast feeding babies (B.infantis) Quantity is relevant.Curiously, two kinds of bifidobacterium infantises (B. infantis)The most unfermentable fucose of bacterial strain or sialic acid.
Conclusion:
About bifidobacterium fermentation HMO precursor, prebiotics and the ability of HMO, exist among the bacillus bifidus of test Significant difference.In the middle of 12 kinds of bacillus bifiduss of test, do not have one can ferment sialic acid.About prebiotics, major part is double Discrimination bacillus can be fermented GOS and scFOS, but they unfermentable PDX.Among the bifidobacterium strain of test, only baby Bifidus bacillus (B.infantis) ATCC 15697 and bifidobacterium infantis (B.infantis) M-63 can ferment 6'-SL, 3'- SL, 2'-FL and 3'-FL.Bifidobacterium breve (B.breve) ATCC 15700, bifidobacterium infantis (B.infantis)ATCC 15697 and bifidobacterium infantis (B.infantis) M-63 can ferment LNnT.
Embodiment 38
In this embodiment, make the cell culture model of employment small intestinal, evaluate the new tetrose of lactoyl-N-(LNnT), 2'-rock algae Glycosyl lactose (2'FL) and 6'-saliva lactose (6'SL) by induction epithelial cell differentiation and barrier function (cell resistance resists), Facilitating digestion function and promotion antibacterial functions, and prevent feeding intolerance and the ability of necrotizing enterocolitis (NEC).Make With the In vitro culture thing in each stage of the intestinal epithelial tissue representing differentiation, evaluate LNnT, 2'FL and 6'SL and play these protections Property and the ability of beneficial effect.Each right of LNnT, 2'FL, 6'SL of various concentration or these human milk oligosaccharides (HMO) In the presence of oligosaccharide, cultivate epithelial cell, and measure LNnT, 2'FL, 6'SL or tester to cell differentiation, barrier merit Can, digestive function and prevent the impact of antibacterial.
In first experiment, at 37 DEG C, LNnT or 2'FL (concentration is 0 mg/L (" 0 "), 20 mg/L (" 20 "), 200 mg/L (" 200 ") and 2000 mg/L (" 2000 ")) in the presence of, or 6'SL (concentration be 0 mg/mL (" 0 "), 40 Mg/mL (" 40 "), 400 mg/mL (" 400 ") and 4000 mg/mL (" 4000 ")) in the presence of, by HT-29 cell, (it imitates Immature intestinal epithelial cell) cultivate 72 hours in the moistening atmosphere of 5% carbon dioxide.The culture medium used is to be supplemented with Eagle culture medium that the Dulbecco's of 10% hyclone and 2 mM glutamine improves (Life Technologies, Foster City California).For LNnT, tester (" energy ") is by 91.5 mg lactose and 64.2 mg N-acetyl Base lactose amine/L composition；For 2'FL, tester is made up of 133 mg lactose and 67 mg fucose/L；For 6'SL, tester It is made up of 195 mg lactose and 205 mg/L sialic acides.For HT-29 cell, measure LNnT, 2'FL and 6'SL of various level With the tester impact on alkaline phosphatase activities (every milligram of albumen).Alkaline phosphatase activities is the heaviest for nutrient digestion Want, critically important for the decomposition of noxious bacteria lipopolysaccharide molecule of induction inflammation, and be the mark of cell differentiation.Measurement result Being shown in Fig. 8-10, result shows, in the presence of high dose 2'FL, alkaline phosphatase activities significantly improves (thus to be increased thin Born of the same parents' differentiation, digestive function and prevent the adverse effect of antibacterial), the cell processed with LNnT occurs increasing tendency, to 6'SL process Cell there is no positive effect.
Figure 11-13 illustrates LNnT, 2'FL and 6'SL (cell resistance) (cross-film electrical impedance anti-to cell resistance (Transepithelial resistance)) effect, it is the mark of epithelial barrier function, the most higher electrical impedance with Higher barrier function is relevant.Epithelial cell electrical impedance or barrier function are the yardsticks of the epithelial cell function measuring differentiation.Tool Say body, due to cell maturation, formed between cell and connect more closely, produce higher epithelial cell barriers.This screen Barrier prevents macromole, antibacterial or virus to be transferred to another side from the one side of barrier, and this can improve infection, septicemia and NEC Resistance.The following cross-film electrical impedance (Transepithelial resistance) that measures: use and comprise target cell culture Transwell Snapwell dummy slider, and at 37 DEG C, under 95% oxygen and 5% carbon dioxide conditions, proceed to improve In Ussing cabin, it is immersed among the Kreb's solution of modification.Along with ion passive transport strides across multiple monolayer, measure cross-film electricity Impedance.
In testing at second, at 37 DEG C, LNnT or 2'FL (concentration is 0 mg/L (" 0 "), 20 mg/L (" 20 "), 200 mg/L (" 200 ") and 2000 mg/L (" 2000 ")) in the presence of, or 6'SL (concentration be 0 mg/mL (" 0 "), 40 Mg/mL (" 40 "), 400 mg/mL (" 400 ") and 4000 mg/mL (" 4000 ")) in the presence of, by Caco-2 cell, (it imitates More ripe intestinal epithelial cell) cultivate 72 hours in the moistening atmosphere of 5% carbon dioxide.The culture medium used is to be supplemented with Eagle culture medium that the Dulbecco's of 10% hyclone and 2 mM glutamine improves (Life Technologies, Foster City California).For LNnT, tester (" energy ") is by 91.5 mg lactose and 64.2 mg N-acetyl Base lactose amine/L composition；For 2'FL, tester is made up of 133 mg lactose and 67 mg fucose/L；For 6'SL, tester It is made up of 195 mg lactose and 205 mg sialic acid/L.For nutrient digestion, the noxious bacteria lipopolysaccharide molecule of induction inflammation Decomposition for, LNnT, 2'FL and 6'SL of various levels and tester are critically important on the impact of alkaline phosphatase activities, And it is the mark of cell differentiation.To this end, the bigger intestinal tissue of anticipated alkaline phosphatase activities is to inflammation and NEC more resistance. Measurement result is shown in Figure 14-16, and result shows, in the culture that 2'FL processes, has what alkaline phosphatase activities increased Tendency (thus increases cell differentiation, digestive function and prevents the adverse effect of antibacterial), and increasing occurs in the cell processed with LNnT Tendency, the cell processing 6'SL does not has positive effect.
As another symbol of digestive function, for Caco-2 cell, measure LNnT, 2'FL and 6'SL of various level With the tester impact on sucrase active (every milligram of albumen).Measurement result is shown in Figure 17-19, and result shows, at 2'FL In the culture processed, there is the tendency (thus increasing digestive function) of sucrase active, thin to process with LNnT or 6'SL Born of the same parents do not have positive effect.
Figure 20-22 illustrates LNnT, 2'FL and 6'SL impact on cell resistance anti-(cross-film electrical impedance), and it is epithelium screen The mark of barrier function, the most higher electrical impedance is relevant with higher barrier function.Epithelial cell electrical impedance or barrier function are Measure the yardstick of the epithelial cell function of differentiation.Specifically, due to cell maturation, formed between cell and connect more closely Connect, produce higher epithelial cell barriers.This barrier prevents macromole, antibacterial or virus to be transferred to another from the one side of barrier Face, this can improve infection, septicemia and the resistance of NEC.This result shows, LNnT comes for more ripe Caco-2 cell Say, to cell resistance is anti-, there is positive-effect.Following mensuration cross-film electrical impedance (Transepithelial resistance): use Comprise the Transwell Snapwell dummy slider of target cell culture, and at 37 DEG C, in 95% oxygen and 5% carbon dioxide conditions Under, proceed to, in the Ussing cabin improved, be immersed among the Kreb's solution of modification.Along with ion passive transport strides across multiple list Layer, measures cross-film electrical impedance.
Conclusion:
The data of Fig. 8-22 report show, LNnT and 2'FL promotes intestinal function, including digesting, barrier function and prevent known The cell component of induction inflammation.Facilitating digestion function is carried out by increasing digestive enzyme activity (saccharase and alkali phosphatase), permissible Contribute to preventing or reducing the order of severity of feeding intolerance.With to barrier function and the effect that prevents noxious bacteria metabolite In conjunction with, these data provide these HMO of proof and can aid in the ample evidence preventing enteritis and NEC.
Embodiment 39
In this embodiment, by the gastrointestinal barrier function strengthened produced by HMO and healing function, HMO is analyzed to increasing Add TFF3 and other effect and its dose dependent promoting to feed the goblet cell gene expression of toleration.
In mankind's LS174T cell culture model of goblet cell, the HMO that test merges is in inductionMUC2、TFF3、RELMβ、CHST5WithGAL3ST2Ability in terms of expression.Obtain from American Type Culture Collection (ATCC) Mankind LS174T colorectal cancer cell system.At 37 DEG C, at 5% CO2In atmosphere, LS174T cell is maintained at and is supplemented with 10% Fetalplex(Gemini Biosciences)、1.5 g/L Na2CO3, 10 ml/L benzylpenicillins-Streptomycin Solution In the minimum essential medium (minimum essential medium, MEM) of (Gemini Bio-products).From Lars Bode (University of California, San Diego) obtains the HMO merged, and is dissolved in the water of cell cultivation grade In, reach the concentration needed.Subsequently by this solution filter-sterilized, and for cell culture studies.With comprising 0,1 or 5 mg The above-mentioned medium treatment LS174T cell of HMO/mL.
Collect LS174T cell, and be suspended in Trizol reagent, use RNeasy Plus test kit (Qiagen), press According to the description of manufacturer, separate whole RNA.Measure RNA by Nanodrop (Thermo Fisher Scientific) to divide Quality and quantity from thing.Use high power capacity cDNA Reverse Transcriptase kit (Applied Biosystems), by inverse for RNA separator Transcribe, form cDNA, evaluate its gene expression by quantitative PCR.
For quantitative RT-PCR, obtain specificity T aqMAN gene expression test from Applied Biosystems, its bag IncludeMUC2(Hs00159374_m1)、TFF3(Hs00173625_m1)、RELMβ(Hs00395669_m1)、CHST5 (Hs00375495_m1)、GAL3ST2(Hs00223271_m1) andGUSB(Hs99999908_m1) expression test.Use TaqMAN PCR Master Mix (Applied Biosystems), carries out PCR the most in real time.Use Applied Biosystems 7900HT Fast real-time PCR system, reacts in 384 orifice plates, and reaction is duplicate.Use SDS 2.3 Software analysis result, and utilize delta delta Ct method to calculate.By all samples to Gus-β expression normalization, and relatively Fold induction is calculated in undressed tester.Gene expression is expressed as: compared to the multiple of the compared with control cells without HMO Increase.By this experiment in triplicate.Data represent meansigma methods+SEM (n=3 plate of each experiment).With different letter representation systems Meter difference (P < 0.05).
Figure 23 A-23E represents the amalgamation result of three parallel laboratory tests.Specifically, Figure 23 A, 23B and 23C illustrate, compare In control cultures, with the HMO process of at least 1 mg/ml level, addMUC2、TFF3WithRELM β geneExpression.Cup-shaped The expression increase of cytogene is specific and non-general, and this can be by with the HMO process of 1 mg/ml or 5 mg/ml 'sCHST5WithGAL3ST2It is that induction is minimum or shortage induction proves respectively.
It addition, Figure 23 A and 23B showsMUC2WithTFF3The dose dependent expressed increases, and processes level at 1 mg/ml The lower induction (~ 1.5 times) that appropriateness occurs, and more specific increase (~ 2 times) occurs under 5 mg/ml levels.It addition, at 1 mg/ Ml processes under level and 5 mg/ml each process level,RELMβExpression (Figure 23 C) increase (~ 1.5 times).With this phase Instead, under any dosage, do not interfere significantly onCHST5(Figure 23 D) andGAL3ST2The gene expression of (Figure 23 E).Therefore, may be used To conclude, the impact of the HMO some gene expressions on participating in gastrointestinal tract healing response is dose dependent.
These results indicate that HMO promotes the expression of some genes involved by GI barrier function and gastrointestinal tract healing response. First, HMO induction is allMUC2、TFF3WithRELMβThe protein product collaborative work of gene, forms protection gastrointestinal tract defence disease The mucus barrier of substance.Additionally,TFF3Express the protection with the gastrointestinal damage of mammal enterocyte and recover forward Association.In animal model, oralTFF3Process can reduce the damage relevant to various forms colitis.It addition, HMO inductionMUC2Expression, its provide defence gastrointestinal infection and other injury source barrier.Further, HMO inductionRELMβTable Reaching, it is to eliminate relevant albumen to inflammation.Because when there is a large amount of inflammation, tissue injury is difficult to heal, and HMO inductionRELMβInflammation eradicating efficacy also support this healing.HMO pairTFF3、MUC2WithRELMβThe combined effect expressed, by it Cell is healed, diminishes inflammation and promotes the cooperative effect of barrier function, it is possible to prevention necrotizing enterocolitis, and support wound Recover from injury and close.

Claims (10)

1. the human milk oligosaccharides selected from 2'-fucosyllactose and the new tetrose of lactoyl-N-and its combination form is used for dropping in preparation Purposes in the medicine of the sickness rate of the necrotizing enterocolitis of low baby, child or child, wherein said medicine is to comprise Sum is the nutritional composition of the human milk oligosaccharides of 0.001 mg/ml to 20 mg/ml.
2. the purposes of claim 1, wherein said composition comprises 0.001 mg/ml to the 2'-fucosido breast less than 2 mg/ml Sugar.
3. the purposes of claim 1, wherein said composition comprises 0.001 mg/ml to the lactoyl-N-new four less than 0.2 mg/ml Sugar.
4. the purposes of claim 1, wherein said composition comprise further prebiotics, probiotic bacteria, long-chain polyunsaturated fatty acid, In the lactoprotein of antioxidant, the lactoprotein in people source, the lactoprotein of Niu Laiyuan and the people of combination and Niu Laiyuan at least one Kind.
5.6'-saliva lactose, 2'-fucosyllactose and the new tetrose of lactoyl-N-are used for reducing baby, child and child in preparation Necrotizing enterocolitis sickness rate medicine in purposes, wherein said medicine is nutritional composition.
6. the purposes of claim 5, wherein the existence of 6'-saliva lactose, 2'-fucosyllactose and the new tetrose of lactoyl-N-is total Quantity is 0.001 mg/ml to 20 mg/ml.
7. the purposes of claim 5, wherein this nutritional composition comprises 0.001 mg/ml to the 6'-less than 0.25 mg/ml Saliva lactose.
8. the purposes of claim 5, wherein this nutritional composition comprises 0.001 mg/ml to the 2'-rock algae less than 2 mg/ml Glycosyl lactose.
9. the purposes of claim 5, wherein this nutritional composition comprise 0.001 mg/ml to less than 0.2 mg/ml lactoyl- The new tetrose of N-.
10. the purposes of claim 5, wherein how unsaturated comprise prebiotics, probiotic bacteria, long-chain further for this nutritional composition In the lactoprotein of fatty acid, antioxidant, the lactoprotein in people source, the lactoprotein of Niu Laiyuan and the people of combination and Niu Laiyuan At least one.
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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009113861A2 (en) * 2008-03-14 2009-09-17 Friesland Brands B.V. Process for isolating sialic acid containing oligosaccharides, and the compositions containing sialic acid containing oligosaccharides obtainable thereby

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
Human milk oligosaccharides prevent Necrotizing Enterocolitis in neonatal rats;Lar Bode, et al.;《The FASEB Journal》;20100430;第24卷;摘要 *
ヒトミルクオリゴ糖の生理作用;浦島匡 等;《Milk Science》;20081231;第56卷(第4期);第167页右栏第1段，第168页右栏第3段，第170页右栏倒数第1段，第171页左栏第2段 *

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