CN106072654A - 6 ' sialylated lactose purposes in infants and young's nutrient - Google Patents

6 ' sialylated lactose purposes in infants and young's nutrient Download PDF

Info

Publication number
CN106072654A
CN106072654A CN201610421321.8A CN201610421321A CN106072654A CN 106072654 A CN106072654 A CN 106072654A CN 201610421321 A CN201610421321 A CN 201610421321A CN 106072654 A CN106072654 A CN 106072654A
Authority
CN
China
Prior art keywords
purposes
alimentation composition
oligosaccharide
aforementioned
sugar
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
CN201610421321.8A
Other languages
Chinese (zh)
Inventor
B·斯塔尔
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Nutricia NV
Original Assignee
Nutricia NV
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from PCT/NL2010/050239 external-priority patent/WO2011136636A1/en
Application filed by Nutricia NV filed Critical Nutricia NV
Publication of CN106072654A publication Critical patent/CN106072654A/en
Pending legal-status Critical Current

Links

Classifications

    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23LFOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/20Reducing nutritive value; Dietetic products with reduced nutritive value
    • A23L33/21Addition of substantially indigestible substances, e.g. dietary fibres
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23LFOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/40Complete food formulations for specific consumer groups or specific purposes, e.g. infant formula
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00Drugs for immunological or allergic disorders
    • A61P37/02Immunomodulators
    • A61P37/04Immunostimulants
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23VINDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00Food compositions, function of food ingredients or processes for food or foodstuffs

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Immunology (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical & Material Sciences (AREA)
  • Polymers & Plastics (AREA)
  • Food Science & Technology (AREA)
  • Nutrition Science (AREA)
  • Mycology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pediatric Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Coloring Foods And Improving Nutritive Qualities (AREA)
  • Dairy Products (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)

Abstract

The present invention relates to a kind of 6 ' sialylated lactose purposes in infants and young's nutrient.The invention provides the alimentation composition that nutrition is provided for infants and young, wherein apply suitable 6 ' SL absolute magnitudes and the 6 ' SL relative quantity than 3 ' SL.

Description

6 '-sialylated lactose purposes in infants and young's nutrient
The application is the of entitled " 6 '-sialylated lactose purposes in infants and young's nutrient " The divisional application of No. 2011800210644 applications for a patent for invention.Original application correspondence international application PCT/NL2011/050285, Shen Please be on April 27th, 2011 day, priority date be on April 27th, 2010.
Technical field
The invention belongs to the field of infants and young's nutrient.
Background technology
Sialylated oligosaccharide is present in the Ruzhong of mammal and has been found to have biologic importance.Known it There is prebiotic activity, and be described bifidobacterium growth effect (bifidogenic effect).Known sialylated Oligosaccharide also has antisticking effect, thus plays in the intestinal infection that suppression or prevention are caused by pathogen and/or toxin Important function.Known sialylated oligosaccharide concentration in such as Lac Bovis seu Bubali is the lowest, but concentration is the highest in human milk.Due to Most infants formula is prepared with milk elements, so compared with breast-fed babies, the baby of formula feeding has Relatively low sialylated oligosaccharide intake.The important member of sialylated oligosaccharide be 3 '-sialylated lactose (3 '-SL) and 6 '-sialylated lactose (6 '-SL).
Mart í n-Sosa et al (2003) J Dairy Sci 86:52-59 has carried out one about different in age of sucking The comparative study of the sialylated oligosaccharide content of Lac Bovis seu Bubali and human milk in stage.
Asakuma et al. (2007) Biosci Biotechnol Biochem, 71 (6): 1447-1451 have studied The change of people's just sialylated concentration of oligosaccharide in Ruzhong in first three day of age of sucking.Find that the concentration of 3 '-sialylated lactose exists Within 1st day, apparently higher than the 2nd day and the 3rd day, and the mean concentration of 3 '-SL was about 297mg/L in puerperal first three sky.6 '-saliva The level of liquid acidifying lactose is at the 3rd day higher than the 1st day, and in puerperal first three sky, the mean concentration of 6 '-SL is 370mg/L.
WO 2009/059996 relates to the alimentation composition of the secondary infection after prophylaxis of viral infections, including sialic acid Change oligosaccharide, particularly 3 '-SL and 6 '-SL.
In view of the purpose in order to prepare the infants and young's food being similar to human milk as far as possible, this area is it has been recognized that make This group food is rich in containing sialic oligosaccharide, the most sialylated lactose.In view of this point, such as at WO 2009/ Describe in 113861 and separate the most sialylated lactose from Ruzhong to make human infant nutrition rich in sialylated lactose Method.And do not differentiate between 3 '-SL and 6 '-SL.
Summary of the invention
Surprisingly, it was found that in order to 6 ' actually existed in human milk-sialylated lactose (6 '-SL) quantity Consistent, need 6 '-SL of the higher amount that preparation ratio is used now in infant formula.
Further, the present inventors have additionally discovered that, be applied to now infant formula 3 '-SL and 6 '-SL relative quantity or Ratio is compared, and actually exists in the relative quantity of 3 ' in human milk-sialylated lactose (3 '-SL) and 6 '-SL and becomes 3 '-SL and account for phase To relatively low ratio.
Therefore, in short, the inventors discovered that, in order to be similar to human milk as far as possible and in order to preferably reach sialic acid Change the more optimal prebiotic activity of oligosaccharide (preferably 6 '-SL and 3 '-SL), bifidobacterium growth effect and/or anti-stick Effect, infant formula needs to prepare, especially with regard to sialylated oligosaccharide (preferably being different from present practice 6 '-SL and 3 '-SL) amount.In doing so, will realize improve intestinal physiology and/or health, preferably implement suppression or Improvement in terms of the intestinal infection that prevention is caused by pathogen and/or toxin.
Detailed description of the invention
Therefore, the present invention relates to a kind of method providing nutrition for baby, described method includes that giving one comprises at least The compositions of 1g/L 6 '-sialylated lactose (6 '-SL), wherein the weight ratio of 6 '-SL:3 '-SL is higher than 2.
The present invention can also be expressed as, and relates to the compositions that one comprises 6 '-sialylated lactose (6 '-SL) and is used for preparing There is provided the purposes in the alimentation composition of nutrition, described alimentation composition to comprise at least 1g/L 6 '-SL for baby, wherein 6 '- The weight ratio of SL:3 '-SL is higher than 2.
The present invention can also be expressed as, and a kind of comprises at least 1g/L6 '-sialylated breast for provide nutrition for baby The compositions of sugar (6 '-SL), wherein the weight ratio of 6 '-SL:3 '-SL is higher than 2.
The invention still further relates to a kind of alimentation composition, be preferably a kind of infant formula, it is the most caloric that it comprises offer The lipid of 35%-50%, it is provided that the protein of total caloric 7.5%-12.5%, and total caloric 40%-is provided The digestible carbohydrates of 55%, comprises at least 1g/L 6 '-SL further, and wherein the ratio of 6 '-SL:3 '-SL is higher than 2.
6’-SL
Described alimentation composition of the present invention preferably comprises at least 1g/L 6 '-SL, more preferably at least 1.1g/L.This Concentration, more like human milk, is commonly used in infant milk formula, and is therefore preferred.Described alimentation composition of the present invention is preferably Comprise less than 3g/L 6 '-SL, more preferably less than 2.5g/L, more preferably less than 2g/L, more preferably less than 1.5g/L 6 '- SL, more preferably between 1.1g/L to 1.5g/L, more preferably between 1.1g/L to 1.4g/L, more preferably at 1.2g/L Between 1.4g/L.
Described alimentation composition of the present invention further preferably includes 3 '-SL, and the weight ratio of 6 '-SL:3 '-SL is higher than 2.Preferably, the weight ratio of 6 '-SL:3 '-SL is higher than 2.5, preferably higher than 2.8, preferably higher than 3, preferably higher than 3.5, It is preferably higher than 4.Preferably, the weight ratio of 6 '-SL:3 '-SL is less than 6.It is preferably lower than 5.5, is preferably lower than 5.Preferably, The weight ratio of 6 '-SL:3 '-SL is between 2.5 to 5.5, preferably between 3 to 5.
In one embodiment, the described present composition comprises based on described compositions overall dry weight at least The 6 '-SL of 0.7wt%, are based preferably on described compositions overall dry weight between 0.7wt% to 2.1wt%, preferably exist Between 0.8wt% to 1.5wt%, preferably between 0.85wt% to 1.0wt%.
Described alimentation composition of the present invention can be prepared by the method preparing infant milk formula, and described method includes a) adding Add the non-digestible property oligosaccharide from Lac Bovis seu Bubali, b) add 6 '-SL.
6 '-SL are commercially available and can buy from Sigma-Aldrich.6 '-SL can also be by through metabolism The escherichia coli (E.coli) of transformation synthesize, described escherichia coli expression Photobacterium (Photobacterium sp.) The multi-functional sialyltransferase of one of JT-ISH-224, as Drouillard et al. submits at present in version Described in Carbohydrate Research.The evidence of correction is available from http://www.sciencedirect.com/ science?_ ob=ArticleURL&_udi=B6TFF-4YG1M15-1&_user=3112367&_coverD ate=02% 2F24%2F2010&_rdoc=1&_fmt=high&_orig=search&_sort=d&_doca nchor=&view= C&_searchS trId=1311365313&_rerunOrigin=scholar.google&_acct=C00005 9787&_ Version=1&_urlVersion=0&_userid=3112367&md5= ec8dccad77c1e06a5b102da46d8403b6。
Non-digestible property oligosaccharide in addition to 6 '-sialylated lactose and 3 '-sialylated lactose
Described alimentation composition preferably includes non-digestible property oligosaccharide (NDO, non-in addition to 6 '-SL and 3 '-SL digestible oligosaccharides).Preferably, described NDO stimulation of bifidobacteria in addition to 6 '-SL and 3 '-SL And/or the growth of the growth of lactobacillus, more preferably stimulation of bifidobacteria.Bacillus bifidus and/or the increasing of lactobacillus content Add the formation stimulating healthy gut flora.Described NDO is preferably the most digested in intestinal or the most digested, described Digestion is to carry out, described NDO by being present in the acid of people's upper digestive tract (particularly in small intestinal stomach function regulating) or the effect of digestive enzyme Fermented by people's intestinal microbial population.Such as, sucrose, lactose, maltose and common maltodextrin are considered as digestible.
Preferably, the described present composition comprises DP in the range of 2 to 250, the non-digestible property of more preferably 2 to 60 Oligosaccharide.Described non-digestible property oligosaccharide is preferably selected from least one of following component, more preferably at least two kinds, preferably It is at least three kinds: oligofructose, oligomeric galactose, oligomeric xylose, arabinooligosaccharides, arabinooligosaccharides galactose, oligomeric Glucose, low Chitosan, oligomeric glucose mannose, oligomeric galactose mannose, Oligomeric manna sugar, containing sialic oligosaccharide And uronic acid oligosaccharides.The group of oligofructose includes inulin, and the group of oligomeric galactose includes transgalactooligosac,harides or β-low Poly-galactose, the group of oligomeric glucose includes cyclodextrin, gentian oligose and aspergillus niger oligosaccharide and non-digestible Xing Ju Portugal Grape sugar, the group of oligomeric galactose mannose includes the guar gum of partial hydrolysis, and the group of uronic acid oligosaccharides includes galacturonic acid Oligosaccharide and pectin degradation product.
It is highly preferred that the described present composition includes selected from oligofructose, β-oligomeric galactose and uronic acid oligosaccharides In at least one, more preferably at least two kinds, most preferably three kinds.It is highly preferred that described compositions includes β-oligomeric gala Sugar.
In a preferred embodiment, described compositions includes the mixture of inulin and short chain oligofructose.One In individual preferred embodiment, described compositions includes the mixture of oligomeric galactose and oligofructose, wherein said oligomeric fruit Sugar is selected from short chain oligofructose and inulin, preferably inulin.The mixture of the non-digestible property oligosaccharide that at least two is different has Have stimulated the degree that the beneficial bacteria in intestinal microbial population reaches bigger sharply.Preferably, different non-digestible of the two In the mixture of property oligosaccharide (preferably oligomeric galactose and oligofructose), both weight ratios are between 25 to 0.05, more Preferably between 20 to 1.Oligomeric galactose (preferably β-oligomeric galactose) more can stimulation of bifidobacteria.Preferably, institute State oligomeric galactose (preferably β-oligomeric galactose) that the present composition includes that the degree of polymerization (DP) is 2 to 10 and/or DP is 2 To the oligofructose of 60.
Described oligomeric galactose is preferably β-oligomeric galactose.In an especially preferred embodiment, send out for described Bright compositions includes β-oligomeric galactose ([galactose] n-glucose;Wherein n is the integer from 2 to 60, i.e. 2,3,4,5, 6、....、59、60;Preferably n is selected from 2,3,4,5,6,7,8,9 and 10), wherein said galactose units is mainly by β key (linkage) link together.β-oligomeric galactose is also referred to as transgalactooligosac,harides (TOS).Such as, β-oligomeric galactose It is with trade mark Vivinal(TM)(Borculo Domo Ingredients, Netherlands) sells.Another suitable source is Bi2Munno(Classado).Preferably, described TOS includes β-Isosorbide-5-Nitrae based on total key number meter at least 80% and β-1,6 keys, more It is preferably at least 90%.
In order to comprise, to have DP or average DP be 2 to 250 to oligofructose, preferably 2 to 100, even more preferably 10 to 60 The NDO of fructose units chain of β-connection.Oligofructose includes the polyfructosan of inulin, levan and/or mixed type.A kind of special Not preferably oligofructose is inulin.The oligofructose being suitable for described compositions is also commercially available, such asHP(Orafti).Preferably, the average poly-DP of described oligofructose is more than 20.
Uronic acid oligosaccharides preferably obtains from pectin degradation product.The most described present composition preferably includes DP It it is the pectin degradation product of 2 to 100.Preferably, described pectin degradation product is from apple pectin, beet pectin and/or citrus fruit Prepared by glue.Preferably, described uronic acid oligosaccharides is galactoronic acid oligosaccharides.Preferably, described compositions include FL with And the one in oligomeric galactose and uronic acid oligosaccharides.
Except 6 '-SL and 3 '-SL, most preferably, described compositions includes β-oligomeric galactose, oligofructose and alduronic acid Oligosaccharide.Find described conjugate and 6 '-SL and 3 '-SL synergism.β-oligomeric galactose: oligofructose: uronic acid oligosaccharide The weight ratio of sugar is preferably (20 to 2): 1:(1 to 20), more preferably (20 to 2): 1:(1 to 10), even more preferably (20 arrive 2): 1:(1 to 3), it is even more preferably (12 to 7): 1:(1 to 2).Most preferably, described weight ratio is about 9:1:1.1.
Preferably, the non-digestible property oligosaccharide that the every 100ml of described alimentation composition comprises 100mg to 4g (includes 6 '-SL With 3 '-SL), the non-digestible property that more preferably 500mg to 3g, the most every 100ml comprise 800mg to 2g is oligomeric Sugar.Based on dry weight meter, described compositions preferably comprises the non-digestible property oligosaccharide of 0.5wt% to 25wt% and (includes 6 '-SL With 3 '-SL), more preferably 1wt% to 15wt%, even more preferably 5wt% to 10wt%.The non-digestible property of relatively low amount is low In terms of polysaccharide beneficial bacteria in stimulating flora (microbiota) less effective, but too high amount will cause flatulence with The side effect of abdominal discomfort.
Alimentation composition
Described alimentation composition is not human milk.Described alimentation composition of the present invention preferably gives through enteral, the most oral Give.
Described alimentation composition of the present invention is preferably infant formula.Described alimentation composition of the present invention can be advantageously used for The complete nutrition thing of baby.The described present composition preferably comprises lipid components, protein component becomes with carbohydrate Divide, and the present composition gives the most in liquid form.The present invention includes being dried food, preferably powder, and it is with closing In the explanation that described dry foodstuff mixture is mixed with the liquid (preferably water) being suitable for.
Described alimentation composition of the present invention preferably comprises lipid, protein and digestible carbohydrates, wherein said Lipid components provide the most caloric 5% to 50%, described protein component provide the most caloric 5% to 50%, described in disappear The property changed carbohydrate component provides the most caloric 15% to 85%.Advantageously, described lipid components provides the most caloric 20% to 50%, described protein component provides the most caloric 5% to 30%, and described digestible carbohydrates composition provides The most caloric 30% to 70%.Preferably, described lipid components provides the most caloric 35% to 50%, and described protein becomes Dividing and provide the most caloric 7.5% to 12.5%, described digestible carbohydrates composition provides the most caloric 40% to arrive 55%.Account for total caloric % for calculating described protein component, need to consider to be provided by described protein, peptide and aminoacid Gross energy.
Described alimentation composition preferably comprises at least one selected from animal lipid (except people's lipid) and vegetable lipid Lipid.Preferably, the described present composition includes that vegetable lipid is oily with selected from fish oil, animal oil, algae oil, fungal oil and antibacterial The conjugate of at least one oil.The described present composition preferably includes long-chain polyunsaturated fatty acid (LC-PUFA). LC-PUFA be a length of 20-24 carbon atom, be preferably 20 or 22 carbon atoms containing two or more unsaturated bonds Fatty acid or fatty acyl chain.It is highly preferred that the described present composition comprises eicosapentaenoic acid (EPA, n-3), 22 carbon Acid (DHA, n-3) and/or arachidonic acid (ARA, n-6).
Preferably, the described present composition includes at least 0.1wt% based on total lipid content meter, preferably at least The LC-with 20-22 carbon atom of 0.25wt%, more preferably at least 0.6wt%, even more desirably at least 0.75wt% PUFA。
Since it is desired that human milk simulating as much as possible, LC-PUFA's (particularly there is the LC-PUFA of 20-22 carbon atom) The 3wt% of the 6wt% of content, preferably more than total lipid content, no more than total lipid content.Described LC-PUFA Can provide as free fatty, as a triglyceride, with triglyceride form, with monoglyceride form, with phospholipid shape Formula, or provide as one of the above or multiple mixture.The described present composition preferably comprises based on total buttermeter 5wt%-75wt%, the polyunsaturated fatty acid of preferably 10wt%-50wt%.
Protein in described alimentation composition is preferably chosen from: inhuman animal protein (preferably lactoprotein), Phytoprotein (preferably soybean protein, pea protein and/or rice protein), its hydrolyzate, its free amine group Acid and mixture thereof.Described alimentation composition preferably contains casein, milk surum, the casein of hydrolysis and/or the milk surum of hydrolysis Albumen.Preferably, described protein includes whole protein, the most complete milk albumin and/or complete cattle cheese Protein matter.
Described alimentation composition preferably contain selected from sucrose, lactose, glucose, fructose, corn-syrup solids, starch and The digestible carbohydrates of maltodextrin, more preferably lactose.
Preferably, described liquid food does not have an excessive caloric density, but still provide enough calorie with Feeding infant.Therefore, described liquid food preferably has the caloric density between 0.1 to 2.5kcal/ml, the most excellent Elect the caloric density between 0.5 to 1.5kcal/ml, the caloric density between most preferably 0.6 to 0.8kcal/ml as.
Preferably, described alimentation composition includes nucleotide and/or nucleoside, more preferably nucleotide.Preferably, described group Compound comprises 5'-CMP, 5 '-UMP, AMP, 5'-GMP and/or 5 '-monophosphate Inosine, more preferably 5'-CMP, 5 '-UMP, AMP, 5'-GMP and 5 '-mono-phosphorus Acid inosine.The every 100 grams of described compositions dry weights of the most described compositions comprise 5 to 100mg, more preferably 5 and arrive 50mg, optimum Selection of land 10 arrives nucleotide and/or the nucleoside of 50mg.
Infants and young
Described the inventive method can be advantageously applied for the child of the human infant of 0-36 month, and more preferably 0-18 is individual The human infant of the moon, the human infant of more preferably 0-12 month, the human infant of even more preferably 0-6 month.0-36 The baby of the moon includes child.In one embodiment, child's age is more than 6 months by 36 months, or more than within 12 months, arriving 36 months, or more than 18 months to 36 months.In order to pathogen causes the risk of infection be down to minimum, with according to the present invention's The proportions infant formula of the amount of 6 '-SL and 6 '-SL and 3 '-SL is favourable.Preferably, with the 6 '-SL according to the present invention Amount and proportions 1 stage of 6 '-SL and 3 '-SL and the infant formula in 2 stages.Preferably, with the 6 '-SL according to the present invention Amount and the infant formula in proportions 1 stage of 6 '-SL and 3 '-SL.1 stage formulation is for being preferably less than 6 months Baby provides nutrition, it is therefore preferable to the baby of preferably smaller than 4 months provides nutrition.
Embodiment
Embodiment 1 measures 6 '-SL in breast milk
Material and method
Serological test
In three days puerperal, the women passing through hemagglmination collector test determination Lewis blood group the same day of blood sampling.Make With corresponding red blood cell suspension (3%-5% red blood cell suspension is in 0.9%NaCl) and monoclonal anti LeaWith anti-LebAntibody (Immucor,Germany and BAG, Lich, Germany) check hemoagglutination.In room temperature Hatch 15 minutes.Due to the difference between serological test and chromatogram, it was repeated some blood hemocytees 18-25 month puerperal Agglutination test (Thurl et al.1998Milchwissenschaft 53:127-129).The women of reception test does not has at that time Conceived.
Collect sample
All mothers have signed written comment and have agreed to participate in this research, Dresden, Germany university hospital (university hospital of Dresden, Germany) Ethics Committee have approved this research design.30 Caucasia Women lives in area, Dresden, and they at 20 to 35 years old and have given birth to healthy babies at the age, and described baby is during studying For Pure breast feeding.175 whole breast milk samples are mainly acquired in the following time interval including 7 main dates: 3rd day, 2-5 days puerperal;8th day, d6-d9;15th day, d13-d18;22nd day, d20-d26;30th day, d28-d33;60th My god, d57-d65;90th day, d88-d96.If motherhood have collected the milk sample corresponding to above-mentioned time interval of unnecessary This, then all of sample is analyzed with the arithmetic mean of instantaneous value of concentration of oligosaccharide.Once to from Frankfurt, Germany (Frankfurt/Main) area 6 Caucasians, women preliminary examination in, the 7th day puerperal and the 60th day two 24 hours In cycle, inventor does not find that any obvious oligosaccharide changes (data are unlisted).But, even the least in order to get rid of Daylight effect, the sampling time in this research is fixed on when feeding the morning.Described milk sample this generally the morning 6-10 point upper Using (mid-feed) Sampling techniques in feeding to collect between the period of the day from 11 a.m. to 1 p.m, this technology was proved to be a kind of in the past and divided for carbohydrate The suitable Sampling techniques of analysis.It is extruded into manual for the small sample of about 5-10ml in plastic containers in the centre fed.By milk sample This is freezing immediately and is stored at 20 DEG C until analyzing.
The chromatography of oligosaccharide
Sample preparation includes gel permeation chromatography purification, and by method (the Thurl et having been described above Al.1996Anal Biochem.235:202-206) carry out HPAEC analysis.In simple terms, human milk sample is heated at 70 DEG C 30 minutes.In 1ml human milk, add 0.1ml contain internal standard substance stachyose and galacturonic acid aqueous acid.Then by described sample This centrifugal and ultrafiltration (Millipore Centrifree, 30kDa retain).Use Toyopearl HW 40 (S) post (1, 6x80cm TosoHaas, Stuttgart, Germany) pass through gel permeation chromatography by described protein and lipopenic sample This fractionated is lactose, neutral oligosaccharide and acidic oligomer sugar.Carbohydrate fraction is washed with water (flow velocity 1ml/min) And be monitored by refractive index detection.Lactose fraction is abandoned;Neutral and acidic fraction HPAEC-PED analyzes.Acid low The elution requirement of polysaccharide is 0-8min, 100mM NaOH/20mM NaOAc;8-30min,100mM NaOH/20-80mM NaOAc;30-55min,100mM NaOH/80-200mM NaOAc;55-60min,100mM NaOH/200mM NaOAc.
In order to monitor the possible artificial hydrolytic degradation to especially sensitive sialylated oligosaccharide, free N-acetyl is neural Propylhomoserin (Neu5Ac) is quantitative together with acidic oligomer sugar.The Neu5Ac concentration relative constancy (suckling at Lewis blood group Le (a-b+) In mother, mean concentration is 0.019g/L).The amount of free NeuAc with it be reported that on the same order of magnitude, and in suckling The NeuAc that the oligosaccharide of about 2% and 4% combines is corresponded respectively to during beginning and after three months.Therefore, it can get rid of by saliva The obvious degradation to acidic oligomer sugar that acid enzyme effect or heat treated cause.
Statistical analysis
The data analyzed by statistical method are made up of single concentration of oligosaccharide or total by different carbohydrates The concentration composition of sum.Except total neutral oligosaccharide and total acidic oligomer sugar, the carbon water of the most total nuclear structure and fructose Compound is added up to respectively: core Lac=Lac+3-FL+2 '-FL+LDFT+3 '-SL+6 '-SL;Core LNT=LNT+LNFP I+ LNFP II+LNDFH I+LNDFH II+LSTa+LSTb+DSLNT;Core LNnT=LNnT+LNFP III+LSTc;Core LNH= LNH+2’-F-LNH+3’-F-LNH+2’,3’-DF-LNH;Fuc α 1-2Gal=2 '-FL+LDFT+LNFP I+LNDFH I+2 '- F-LNH+2’,3’-DF-LNH;Fuc α 1-4GlcNAc=LNFP II+LNDFH I+LNDFH II;Fuc α 1-3Glc=3-FL+ LDFT+LNDFH II;Fuc α 1-3GlcNAc=LNFP III+3 '-F-LNH+2 ', 3 '-DF-LNH.
Data set presses two factor tissues, respectively three breast milk groups and seven times of nursing.Further, since different samples Quantity, data set is the most uneven.(have the ursing mother of Lewis blood group Le (a-b+)) in breast milk group 1 109 samples altogether In the time being assigned to 10 to 21 sampling ranges, but (there is the non-ursing mother of Lewis blood group Le (a+b-) in the 2nd group; 28 samples) time of nursing by 3-5 sample representation, in the 3rd group, (have the ursing mother of Lewis blood group Le (a-b-);17 Sample) by 2-3 sample representation.Therefore, the several method of analysis concentration of oligosaccharide meansigma methods is applied.In the 1st group of situation, Then use Student-Newman-Keuls inspection to compare time of nursing first by one factor analysis of variance (ANOVA) Meansigma methods.Two factors ANOVA using type III quadratic sum are used for comparing the meansigma methods of three breast milk groups, then calculate minimum Mean value of square.Therefore, each cell mean without departing from and can compare together completely.Difference Tukey-Kramer of meansigma methods Method is checked on the significance level of 5%.In whole two variate models, often group and the sample participating in women of each time Between this concentration, difference produces experimental error.Generally, from oligomeric in the breast milk of the same breast milk group women of given time of nursing Sugar concentration is alterable height.Due to the interindividual variation that these are huge, although there being notable difference on surface, in same situation (P > 5%) it is not significantly different between average.
The concentration of oligosaccharide trend during suckling is simulated with regression analysis.Notable regression coefficient has carried out simple line Property return and matching that secondary and cubic polynomial return and inspection.If regression coefficient is notable (P < 5%), accept this mould Type.All regression analyses are carried out with single numerical value.All calculating uses SAS system to complete (SAS Institute Inc.2002-2003SAS/STAT release 9.1SAS Institute Inc.,Cary,NC,USA)。
Result
Carbohydrate fraction
The acidic oligomer sugar of six kinds of as shown in table 1 main non-fucosylations, 3 '-SL, 6 '-SL, LSTa, LSTb, LSTc, DSLNT, can measure with chromatograph.These carbohydrate summations approximation represents the acidic oligomer sugar in human milk Fraction.Due to the importance of Lewis blood group system, these sugar are also checked respectively according to described three breast milk groups.All three The milk sample planting breast type originally demonstrates six kinds of acidic oligomer sugar as above.The amount of described acidic oligomer sugar fraction is three mothers Breast group do not has significant difference.It addition, all breast milk groups show about three times of similar acid sugar concentration during studying Decline.
The structure of the acid breast oligosaccharide measured in this research of table 1.
3 '-SL, 3 '-sialylated lactose;6 '-SL, 6 '-sialylated lactose;LSTa-c, sialylated lactose-N-four Sugar a-c (Sialyllacto-N-tetraoses a-c);DSLNT, two sialylated lacto-N-tetraose (Disialyllacto- N-tetraose)。
Acidic saliva acidifying oligosaccharide
The mean concentration of the described six kinds of acidic oligomer sugar measured in this research shows in table 2.Quantitatively 6 '-SL are The most important acidic carbohydrate in current all Ruzhongs.Detect 3 '-SL of moderate quatity, LSTc and DSLNT, but The concentration level of LSTa and LSTb is less than 0.1g/L.The individually mean concentration of acid sugar, although in some cases in statistics Differ on, change the most to a great extent in three breast milk groups, thus confirm about whole carbohydrate level The result divided.
Similarly, the time effect of breast milk group 1 in table 2 and the trend phase of other breast milk groups (data are unlisted) are shown Seemingly.The concentration of 6 '-SL reaches peak value in the transition period breast milk of the 8th day, until after Fen Mian the 90th day have dropped at least 3 times. LSTc, also contains Neu5Ac α 2-6Gal-key, have dropped about 5 times during studying in a similar fashion.3 '-SL are in age of sucking After 1st stage was decreased obviously, with the horizontal expression of relative constancy in ripe breast milk.LSTa, has Neu5Ac α 2-3Gal-key Secondary acid sugar, its concentration declines producing one week after, to such an extent as to is not detected by several breast milk samples after one month. By contrast, the concentration of the LSTb with Neu5Ac α 2-6GlcNAc-key increases in first month and keeps later relatively Constant.DSLNT, the unique two sialylated carbohydrates analyzed, a kind of mixing between LSTa and LSTb Structure, demonstrates the highest time graph.
Table 2. acidic oligomer sugar1)Concentration (g/L)
1)The average having same letter is the most significantly different;Student-Newman-Keuls inspection is compared in group 1, Tukey-Kramer inspection is for the comparison of the least square average (as the result of unbalanced data) of 1-3 group.
Discuss
Acidic oligomer sugar
Six kinds of acidic oligomer sugar that this research measures do not demonstrate great difference in three breast milk groups.This is the most unexpectedly It is outer because these sugar lack fucose moiety.Acid sugar main in this research, the concentration of 6 '-SL is beyond being reported from other groups Amount at least twice, but the concentration of DSLNT relatively low (Coppa et al., 1999Acta Paediatr.Suppl.430:89-94;Martin-Sosa et al.,2003J Dairy Sci.86:52-59;Asakuma et al.,2007Biosci Biotechnol Biochem.71:1447-1451;Bao et al.,2007Anal Biochem.370:206-214).The amount that 3 '-SL, amount and Asakuma et al. of LST a, LSTb and LSTc are detected is in approximation In the range of, the concentration reported less than Coppa et al., the numerical value found higher than Bao et al..Although from difference research (bag Include this research) quantitative result show huge difference, but generally had been found that acid sugar in age of sucking in first month Being decreased obviously of fraction entirety and great majority individually sugar.
6 '-SL and LSTc decline in a similar manner, this following hypothesis of true support: single sialyltransferase, Being probably ST6Gall, unique 2 type structures accepted participate in the biosynthesis of these carbohydrates.LSTc more significantly under Fall can be explained with the decline of the precursor core LNnT of LSTc, but the amount of the precursor lactose of 6 '-SL is producing one week after Rear holding is constant.The 3 '-SL that during research, little degree declines can be synthesized (two kinds of α 2,3-by ST3Gal IV or ST3Gal VI 2 type structures are preferentially worked by sialyltransferase), and it is the most to the inventors discovered that secondary acid sugar LSTa declines, Can not or can only partly detect behind 2 and 3 months.The present inventor guesses the 2,3-sialic acid preferentially worked 1 type structure Transferring enzyme ST3Gall III participates in the biosynthesis of LSTa and DSLNT.LSTb is unique increase in first month puerperal Acid sugar, the result before which demonstrating.So-called ST6GlcNAc can shift sialic acid moities to the GlcNAc of near-end, produces Raw LSTb and DSLNT (a kind of oligosaccharide showing that α 2,6-connects and α 2,3-connection neuraminic acid).
Embodiment 2 infant formula
The every 100ml of infant formula (dry weight 13.9g) comprises:
1.4g protein (milk surum and casein)
7.3g digestible carbohydrates (includes lactose)
3.6g fat (vegetablefats, fish oil)
1.03g non-digestible property oligosaccharide, wherein has 120mg 6 '-SL, 30mg 3 '-SL, 80mg 2 '-fucosido breast Sugar, 720mg β-oligomeric galactose and 80mg oligofructose
Farther include: choline, inositol, taurine, mineral, trace element and vitamin known in the art.
Embodiment 3 child's dairy compositions
Child's dairy compositions (for 1-3 year baby's design) every 100ml (67kcal;Dry weight 15.1g) including:
1.5g protein (lactalbumin/casein 1/1w/w)
8.5g digestible carbohydrates (wherein has 6.0g lactose, 1.1g maltodextrin)
3.0g fat (vegetablefats)
1.23g non-digestible property oligosaccharide, wherein has 120mg 6 '-SL, 30mg 3 '-SL, 80mg 2 '-fucosido breast Sugar, 900mg β-oligomeric galactose and 100mg oligofructose
Mineral, trace element, vitamin known in the art, include choline and taurine.

Claims (12)

1. the compositions comprising 6 '-sialylated lactose (6 '-SL) provides the nutrient combination of nutrition for being prepared as baby The purposes of thing, described alimentation composition comprises at least 1g/L 6 '-SL, and the ratio of wherein 6 '-SL:3 '-SL is higher than 2.
Purposes the most according to claim 1, the concentration of wherein said 6 '-SL is at least 1.1g/L.
3., according to the purposes of claim 1 or 2, the ratio of wherein said 6 '-SL:3 '-SL is higher than 3.
4., according to the purposes of aforementioned any one of claim, the ratio of wherein said 6 '-SL:3 '-SL is higher than 4.
5. according to the purposes of aforementioned any one of claim, wherein said alimentation composition farther include selected from oligofructose and The non-digestible property oligosaccharide of oligomeric galactose.
6., according to the purposes of aforementioned any one of claim, wherein said alimentation composition farther includes selected from galacturonic acid Oligosaccharide and the uronic acid oligosaccharides of pectin degradation product.
7., according to the purposes of aforementioned any one of claim, wherein said compositions includes providing total caloric 35%-50% Lipid, it is provided that the protein of total caloric 7.5%-12.5%, and digesting of total caloric 40%-55% is provided Property carbohydrate.
8., according to the purposes of aforementioned any one of claim, wherein said alimentation composition is for providing to the baby of 0-36 month Nutrition.
9., according to the purposes of aforementioned any one of claim, wherein said alimentation composition is for providing to the baby of 0-6 month Nutrition.
10. an alimentation composition, including providing total caloric 35%-50% fat, it is provided that total caloric 7.5%- 12.5% protein, and total caloric 40%-55% digestible carbohydrates is provided, and farther include 1-3g/L 6 '-SL, wherein the ratio of 6 '-SL:3 '-SL is between 2.5 to 5.5.
11. alimentation compositions according to claim 10, farther include β-oligomeric galactose, oligofructose and uronic acid oligosaccharide Sugar.
12. according to the alimentation composition of claim 10 or 11, and it is 1 stage infant formula.
CN201610421321.8A 2010-04-27 2011-04-27 6 ' sialylated lactose purposes in infants and young's nutrient Pending CN106072654A (en)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
NLPCT/NL2010/050239 2010-04-27
PCT/NL2010/050239 WO2011136636A1 (en) 2010-04-27 2010-04-27 Use of 6'-sialyl lactose in infant nutrition
EP10162555 2010-05-11
EP10162555.6 2010-05-11
CN2011800210644A CN102858191A (en) 2010-04-27 2011-04-27 Use of 6'-sialyl lactose in infant and toddler nutrition

Related Parent Applications (1)

Application Number Title Priority Date Filing Date
CN2011800210644A Division CN102858191A (en) 2010-04-27 2011-04-27 Use of 6'-sialyl lactose in infant and toddler nutrition

Publications (1)

Publication Number Publication Date
CN106072654A true CN106072654A (en) 2016-11-09

Family

ID=44080128

Family Applications (2)

Application Number Title Priority Date Filing Date
CN201610421321.8A Pending CN106072654A (en) 2010-04-27 2011-04-27 6 ' sialylated lactose purposes in infants and young's nutrient
CN2011800210644A Pending CN102858191A (en) 2010-04-27 2011-04-27 Use of 6'-sialyl lactose in infant and toddler nutrition

Family Applications After (1)

Application Number Title Priority Date Filing Date
CN2011800210644A Pending CN102858191A (en) 2010-04-27 2011-04-27 Use of 6'-sialyl lactose in infant and toddler nutrition

Country Status (3)

Country Link
EP (1) EP2563165A1 (en)
CN (2) CN106072654A (en)
WO (1) WO2011136647A1 (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115209745A (en) * 2019-12-09 2022-10-18 雀巢产品有限公司 Composition comprising human milk oligosaccharides for use in supporting language development in an individual

Families Citing this family (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
MY166945A (en) 2010-12-31 2018-07-25 Abbott Lab Nutritional formulations including human milk oligosaccharides and long chain polyunsaturated polyunsaturated fatty acids and uses thereof
MX338174B (en) 2010-12-31 2016-04-06 Abbott Lab Methods for reducing the incidence of oxidative stress using human milk oligosaccharides, vitamin c and anti-inflammatory agents.
NZ612472A (en) 2010-12-31 2015-02-27 Abbott Lab Nutritional compositions comprising human milk oligosaccharides and nucleotides and uses thereof for treating and/or preventing enteric viral infection
CN103391783A (en) 2010-12-31 2013-11-13 雅培制药有限公司 Methods of using human milk oligosaccharides for improving airway respiratory health
EP3338784B1 (en) 2010-12-31 2020-07-22 Abbott Laboratories Human milk oligosaccharides for modulating inflammation
NZ612455A (en) 2010-12-31 2015-02-27 Abbott Lab Human milk oligosaccharides to promote growth of beneficial bacteria
US9539269B2 (en) 2010-12-31 2017-01-10 Abbott Laboratories Methods for decreasing the incidence of necrotizing enterocolitis in infants, toddlers, or children using human milk oligosaccharides
WO2012107865A2 (en) * 2011-02-10 2012-08-16 Wyeth Llc Modulation of growth of bifidobacteria using a combination of oligosaccharides found in human milk
SG2014013478A (en) 2011-08-29 2014-05-29 Abbott Lab Human milk oligosaccharides for preventing injury and/or promoting healing of the gastrointestinal tract
EP2836218A4 (en) * 2012-04-13 2015-10-21 Trustees Boston College Prebiotic compositions and methods of use
EP2745705A1 (en) * 2012-12-18 2014-06-25 Abbott Laboratories Nutritional use of human milk oligosaccharides
ES2725464T3 (en) 2014-09-25 2019-09-24 Nestle Sa Infant formula system with adaptive levels of human milk oligosaccharides (OLH)
US20180103675A1 (en) * 2016-10-14 2018-04-19 Mead Johnson Nutrition Company Personalized pediatric nutrition products comprising human milk oligosaccharides
JP2021505171A (en) * 2017-12-08 2021-02-18 イェンネワイン バイオテクノロジー ゲーエムベーハーJennewein Biotechnologie GmbH Spray-dried sialyll lactose

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1406111A (en) * 2000-02-17 2003-03-26 惠氏公司 Nutritional formulation containing prebiotic substances
CN1863463A (en) * 2003-06-23 2006-11-15 雀巢技术公司 Nutritional formula for optimal gut barrier function
WO2010002241A1 (en) * 2008-06-30 2010-01-07 N.V. Nutricia Nutritional composition for infants delivered via caesarean section
CN102065872A (en) * 2008-05-27 2011-05-18 雀巢产品技术援助有限公司 Probiotics to improve gut microbiota

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
NL1027262C2 (en) * 2004-04-08 2005-10-13 Friesland Brands Bv Composition for reducing intestinal wall permeability, used in e.g. baby food, comprises whey protein, proline and sialic acid
EP2060257A1 (en) * 2007-11-08 2009-05-20 Nestec S.A. Prevention and treatment of secondary infections following viral infection
NL2001377C2 (en) 2008-03-14 2009-09-15 Friesland Brands Bv Process for isolating sialic acid-containing oligosaccharides, as well as the compositions containing sialic acid-containing oligosaccharides.
EP2143341A1 (en) * 2008-07-08 2010-01-13 Nestec S.A. Nutritional Composition Containing Oligosaccharide Mixture

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1406111A (en) * 2000-02-17 2003-03-26 惠氏公司 Nutritional formulation containing prebiotic substances
CN1863463A (en) * 2003-06-23 2006-11-15 雀巢技术公司 Nutritional formula for optimal gut barrier function
CN102065872A (en) * 2008-05-27 2011-05-18 雀巢产品技术援助有限公司 Probiotics to improve gut microbiota
WO2010002241A1 (en) * 2008-06-30 2010-01-07 N.V. Nutricia Nutritional composition for infants delivered via caesarean section

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
YUANWU BAO ET AL.: "Simultaneous quantification of sialyloligosaccharides from human milk by capillary electrophoresis", 《ANALYTICAL BIOCHEMISTRY》 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115209745A (en) * 2019-12-09 2022-10-18 雀巢产品有限公司 Composition comprising human milk oligosaccharides for use in supporting language development in an individual

Also Published As

Publication number Publication date
EP2563165A1 (en) 2013-03-06
CN102858191A (en) 2013-01-02
WO2011136647A1 (en) 2011-11-03

Similar Documents

Publication Publication Date Title
CN106072654A (en) 6 &#39; sialylated lactose purposes in infants and young&#39;s nutrient
US11135290B2 (en) Fucosyllactose as breast milk identical non-digestible oligosaccharide with new functional benefit
US11090321B2 (en) Mixture of non-digestible oligosaccharides for stimulating the immune system
CN101945589A (en) Use of non-digestible carbohydrates for improving intestinal microbiota
EP2563166B1 (en) Use of human milk oligosaccharides in infant nutrition
TW201225852A (en) Oligosaccharide mixture and food product comprising this mixture, especially infant formula
CN101987107A (en) Immunemodulating oligosaccharides
WO2011136636A1 (en) Use of 6&#39;-sialyl lactose in infant nutrition
TW201824998A (en) Personalized pediatric nutrition products comprising human milk oligosaccharides
CN1871015B (en) Immunemodulating oligosaccharides
WO2011136637A1 (en) Use of human milk oligosaccharides in infant nutrition
Zhao Oligosaccharides in Food
CA3198961A1 (en) Synthetic compositions comprising lnfp iii and lsta
BR122021007429B1 (en) USE OF 2&#39;-FUCOSYLACTOSIS IN THE MANUFACTURING OF AN ENTERAL COMPOSITION

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
WD01 Invention patent application deemed withdrawn after publication
WD01 Invention patent application deemed withdrawn after publication

Application publication date: 20161109