CN102858191A - Use of 6'-sialyl lactose in infant and toddler nutrition - Google Patents
Use of 6'-sialyl lactose in infant and toddler nutrition Download PDFInfo
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- CN102858191A CN102858191A CN2011800210644A CN201180021064A CN102858191A CN 102858191 A CN102858191 A CN 102858191A CN 2011800210644 A CN2011800210644 A CN 2011800210644A CN 201180021064 A CN201180021064 A CN 201180021064A CN 102858191 A CN102858191 A CN 102858191A
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- alimentation composition
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- composition
- sugar
- galactooligosaccharide
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- 235000016709 nutrition Nutrition 0.000 title claims abstract description 14
- 230000035764 nutrition Effects 0.000 title claims abstract description 13
- TYALNJQZQRNQNQ-JLYOMPFMSA-N alpha-Neup5Ac-(2->6)-beta-D-Galp-(1->4)-beta-D-Glcp Chemical compound O1[C@@H]([C@H](O)[C@H](O)CO)[C@H](NC(=O)C)[C@@H](O)C[C@@]1(C(O)=O)OC[C@@H]1[C@H](O)[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O)[C@H](O)O[C@@H]2CO)O)O1 TYALNJQZQRNQNQ-JLYOMPFMSA-N 0.000 title abstract description 4
- TYALNJQZQRNQNQ-UHFFFAOYSA-N #alpha;2,6-sialyllactose Natural products O1C(C(O)C(O)CO)C(NC(=O)C)C(O)CC1(C(O)=O)OCC1C(O)C(O)C(O)C(OC2C(C(O)C(O)OC2CO)O)O1 TYALNJQZQRNQNQ-UHFFFAOYSA-N 0.000 title 1
- 239000000203 mixture Substances 0.000 claims abstract description 75
- 150000001875 compounds Chemical class 0.000 claims description 35
- 239000008101 lactose Substances 0.000 claims description 26
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims description 25
- 239000002253 acid Substances 0.000 claims description 24
- 229920001542 oligosaccharide Polymers 0.000 claims description 24
- 150000002482 oligosaccharides Chemical class 0.000 claims description 22
- 150000001720 carbohydrates Chemical class 0.000 claims description 21
- 235000014633 carbohydrates Nutrition 0.000 claims description 21
- 235000019621 digestibility Nutrition 0.000 claims description 16
- 150000002632 lipids Chemical class 0.000 claims description 15
- 235000013350 formula milk Nutrition 0.000 claims description 13
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- 108090000623 proteins and genes Proteins 0.000 claims description 12
- 235000021255 galacto-oligosaccharides Nutrition 0.000 claims description 11
- 150000003271 galactooligosaccharides Chemical class 0.000 claims description 11
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- 238000002360 preparation method Methods 0.000 claims description 6
- 239000007857 degradation product Substances 0.000 claims description 5
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- 238000000034 method Methods 0.000 description 11
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- SFMRPVLZMVJKGZ-JRZQLMJNSA-N Sialyllacto-N-tetraose b Chemical compound O1[C@@H]([C@H](O)[C@H](O)CO)[C@H](NC(=O)C)[C@@H](O)C[C@@]1(C(O)=O)OC[C@@H]1[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO)O2)O)[C@@H](NC(C)=O)[C@H](O[C@@H]2[C@H]([C@H](O[C@H]([C@H](O)CO)[C@H](O)[C@@H](O)C=O)O[C@H](CO)[C@@H]2O)O)O1 SFMRPVLZMVJKGZ-JRZQLMJNSA-N 0.000 description 8
- QUOQJNYANJQSDA-MHQSSNGYSA-N Sialyllacto-N-tetraose a Chemical compound O1C([C@H](O)[C@H](O)CO)[C@H](NC(=O)C)[C@@H](O)C[C@@]1(C(O)=O)O[C@@H]1[C@@H](O)[C@H](OC2[C@H]([C@H](OC3[C@H]([C@H](O[C@H]([C@H](O)CO)[C@H](O)[C@@H](O)C=O)O[C@H](CO)[C@@H]3O)O)O[C@H](CO)[C@H]2O)NC(C)=O)O[C@H](CO)[C@@H]1O QUOQJNYANJQSDA-MHQSSNGYSA-N 0.000 description 7
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- 229940029339 inulin Drugs 0.000 description 6
- 230000006651 lactation Effects 0.000 description 6
- 102000011632 Caseins Human genes 0.000 description 5
- 108010076119 Caseins Proteins 0.000 description 5
- SHZGCJCMOBCMKK-DHVFOXMCSA-N L-fucopyranose Chemical compound C[C@@H]1OC(O)[C@@H](O)[C@H](O)[C@@H]1O SHZGCJCMOBCMKK-DHVFOXMCSA-N 0.000 description 5
- 239000008103 glucose Substances 0.000 description 5
- 235000004252 protein component Nutrition 0.000 description 5
- RQFCJASXJCIDSX-UHFFFAOYSA-N 14C-Guanosin-5'-monophosphat Natural products C1=2NC(N)=NC(=O)C=2N=CN1C1OC(COP(O)(O)=O)C(O)C1O RQFCJASXJCIDSX-UHFFFAOYSA-N 0.000 description 4
- SHZGCJCMOBCMKK-UHFFFAOYSA-N D-mannomethylose Natural products CC1OC(O)C(O)C(O)C1O SHZGCJCMOBCMKK-UHFFFAOYSA-N 0.000 description 4
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 4
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 4
- 125000004432 carbon atom Chemical group C* 0.000 description 4
- 239000005018 casein Substances 0.000 description 4
- BECPQYXYKAMYBN-UHFFFAOYSA-N casein, tech. Chemical compound NCCCCC(C(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(CC(C)C)N=C(O)C(CCC(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(C(C)O)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(COP(O)(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(N)CC1=CC=CC=C1 BECPQYXYKAMYBN-UHFFFAOYSA-N 0.000 description 4
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Classifications
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/20—Reducing nutritive value; Dietetic products with reduced nutritive value
- A23L33/21—Addition of substantially indigestible substances, e.g. dietary fibres
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/40—Complete food formulations for specific consumer groups or specific purposes, e.g. infant formula
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
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- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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- General Health & Medical Sciences (AREA)
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- 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)
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- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Abstract
Nutritional composition for providing nutrition to infants and toddlers are provided, wherein adapted absolute amounts of 6'-SL and relative amounts of 6'-SL to 3'-SL are applied.
Description
Technical field
The invention belongs to the field of baby and baby nutrition thing.
Background technology
Sialylated compound sugar is present in mammiferous Ruzhong and has been found to have biology importance.Known they have prebiotic activity, and be described bifidobacterium growth effect (bifidogenic effect).Known sialylated compound sugar also has the antisticking effect, thereby plays an important role in the enteric infection that suppresses or prevent to be caused by pathogen and/or toxin.The concentration of known sialylated compound sugar in cow's milk for example is very low, yet concentration is very high in human milk.Because the most infants prescription is with the milk elements preparation, so compare with breast-fed babies, the baby of formula feeding has lower sialylated compound sugar intake.The important member of sialylated compound sugar is 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 the comparative study of the sialylated oligosaccharide content of cow's milk and human milk in the lactation different phase.
Asakuma et al. (2007) Biosci Biotechnol Biochem, 71 (6): 1447-1451 has studied the just variation of the sialylated concentration of oligosaccharide in Ruzhong of people in first three day of lactation.The concentration of finding 3 '-sialylated lactose obviously was higher than the 2nd day and the 3rd day at the 1st day, and the mean concentration of 3 '-SL is about 297mg/L in first three day in postpartum.The level of 6 '-sialylated lactose was higher than the 1st day at the 3rd day, and the mean concentration of 6 '-SL is 370mg/L in first three day in postpartum.
WO 2009/059996 relates to the alimentation composition for the scabies secondary infection behind the pre-preventing virus infection, comprises sialylated compound sugar, particularly 3 '-SL and 6 '-SL.
In view of in order to prepare the baby that is similar to as far as possible human milk and the purpose of baby food, this area has recognized that, this group food is rich in contains sialic compound sugar, preferred sialylated lactose.Consider this point, for example in WO 2009/113861, described and separated particularly sialylated lactose from the Ruzhong in order to make human infant nutrition be rich in the method for sialylated lactose.Do not distinguish 3 '-SL and 6 '-SL.
Summary of the invention
The inventor is surprised to find, for actually exist in human milk in 6 '-sialylated lactose (6 '-SL) quantity is consistent, need to prepare in infant formula than 6 '-SL of used more a large amount now.
Further, the inventor also finds, compare with the relative quantity that is applied to now 3 ' of infant formula-SL and 6 '-SL or ratio, (relative quantity of 3 '-SL) and 6 '-SL becomes 3 '-SL and accounts for relatively low ratio to actually exist in 3 ' in the human milk-sialylated lactose.
Therefore, in short, the inventor finds, in order to be similar to as far as possible human milk and (to be preferably more best prebiotic activity, bifidobacterium growth effect and/or the antisticking effect of 6 '-SL and 3 '-SL) in order preferably to reach sialylated compound sugar, infant formula need to be prepared to be different from current way, particularly (is preferably the amount of 6 '-SL and 3 '-SL) about sialylated compound sugar.In doing so, with intestinal physiology and/or the health that realizes improving, preferably realize the improvement aspect the enteric infection that suppresses or prevent to be caused by pathogen and/or toxin.
The specific embodiment
Therefore, the present invention relates to a kind of method that nutrition is provided for the baby, described method comprises and gives a kind ofly to comprise at least 1g/L 6 '-sialylated lactose (6 '-SL) composition, wherein the weight ratio of 6 '-SL:3 '-SL is higher than 2.
The present invention can also be expressed as, relate to and a kind ofly comprise 6 '-sialylated lactose (6 '-SL) composition is for the preparation of the purposes in the alimentation composition that nutrition is provided for the baby, described alimentation composition comprises at least 1g/L 6 '-SL, and wherein the weight ratio of 6 '-SL:3 '-SL is higher than 2.
The present invention can also be expressed as, and a kind of baby of being used to provides the 1g/L6 '-sialylated lactose that comprises at least of nutrition, and (6 '-SL) composition, 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 comprises the lipid that total caloric 35%-50% is provided, the protein of total caloric 7.5%-12.5% is provided, and the digestible carbohydrates that total caloric 40%-55% is provided, comprise further at least 1g/L 6 '-SL, 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 1.1g/L at least.This concentration is applied in the baby milk prescription usually more as human milk, and is preferred therefore.Described alimentation composition of the present invention preferably comprises and is less than 3g/L 6 '-SL, more preferably be less than 2.5g/L, more preferably be less than 2g/L, more preferably be less than 1.5g/L 6 '-SL, more preferably at 1.1g/L between the 1.5g/L, more preferably at 1.1g/L between the 1.4g/L, more preferably at 1.2g/L between the 1.4g/L.
Described alimentation composition of the present invention further preferably comprises 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 is higher than 2.8, preferably is higher than 3, preferably is higher than 3.5, preferably is higher than 4.Preferably, the weight ratio of 6 '-SL:3 '-SL is lower than 6.Be preferably lower than 5.5, be 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 composition gross dry weight meter 6 '-SL of 0.7wt% at least, preferably based on described composition gross dry weight meter at 0.7wt% between the 2.1wt%, preferably at 0.8wt% between the 1.5wt%, preferably at 0.85wt% between the 1.0wt%.
Described alimentation composition of the present invention can be by preparing the method preparation of baby milk prescription, and described method comprises the non-digestibility compound sugar that a) adds from cow's milk, b) adds 6 '-SL.
6 '-SL is commercially available and can buys from Sigma-Aldrich.6 '-SL can also come by the Escherichia coli (E.coli) of transforming through metabolism synthetic, a kind of multi-functional sialyltransferase of described Bacillus coli expression Photobacterium (Photobacterium sp.) JT-ISH-224 is submitted at present described in the Carbohydrate of the version Research such as people such as Drouillard.The evidence of proofreading and correct can be available from http://www.sciencedirect.com/science _ ob=ArticleURL﹠amp; _ udi=B6TFF-4YG1M15-1﹠amp; User=3112367﹠amp; CoverDate=02%2F24%2F2010﹠amp; Rdoc=1﹠amp; _ fmt=high﹠amp; _ orig=search﹠amp; _ sort=d﹠amp; _ docanchor=﹠amp; View=c﹠amp; _ searchStrId=1311365313﹠amp; _ rerunOrigin=scholar.google﹠amp; _ acct=C000059787﹠amp; _ version=1﹠amp; UrlVersion=0﹠amp; Userid=3112367﹠amp; Md5=ec8dccad77c1e06a5b102da46d8403b6.
Non-digestibility compound sugar except 6 '-sialylated lactose and 3 '-sialylated lactose
Described alimentation composition preferably includes the non-digestibility compound sugar (NDO, non-digestible oligosaccharides) except 6 '-SL and 3 '-SL.Preferably, described NDO stimulation of bifidobacteria and/or the growth of Bacillus acidi lactici, the more preferably growth of stimulation of bifidobacteria except 6 '-SL and 3 '-SL.The increase of Bifidobacterium and/or Bacillus acidi lactici content stimulates the formation of healthy gut flora.Described NDO is preferably not digested in intestines, and is perhaps only partly digested, and described digestion is to be undertaken by the acid that is present in people's UGI (particularly in small intestine and the stomach) or the effect of digestive ferment, and described NDO is by the fermentation of people's gut flora.For example, sucrose, lactose, maltose and common maltodextrin are considered to digestible.
Preferably, the described present composition comprises DP in 2 to 250 scopes, more preferably 2 to 60 non-digestibility compound sugar.Described non-digestibility compound sugar is preferably and is selected from least a of following composition, more preferably at least two kinds, be preferably at least three kinds: FOS, galactooligosaccharide, xylo-oligosaccharide, low araban, low araban galactolipin, glucose oligosaccharide, oligomeric chitose, glucose oligosaccharide mannose, galactooligosaccharide mannose, Oligomeric manna sugar, contain sialic compound sugar and uronic acid oligosaccharides.The group of FOS comprises inulin, the group of galactooligosaccharide comprises transgalactooligosac,harides or β-galactooligosaccharide, the group of glucose oligosaccharide comprises cyclodextrin, gentian oligose and aspergillus niger compound sugar and non-digestibility polydextrose, the group of galactooligosaccharide mannose comprises the guar gum of partial hydrolysis, and the group of uronic acid oligosaccharides comprises galactoronic acid oligosaccharides and pectin degradation product.
More preferably, the described present composition comprises and is selected from least a in FOS, β-galactooligosaccharide and the uronic acid oligosaccharides, more preferably at least two kinds, most preferably is three kinds.More preferably, described composition comprises β-galactooligosaccharide.
In a preferred embodiment, described composition comprises the mixture of inulin and short chain oligofructose.In a preferred embodiment, described composition comprises the mixture of galactooligosaccharide and FOS, and wherein said FOS is selected from short chain oligofructose and inulin, is preferably inulin.The mixture of at least two kinds of different non-digestibility compound sugar has advantageously stimulated the beneficial bacteria in the gut flora to reach larger degree.Preferably, in the mixture of described two kinds of different non-digestibility compound sugar (being preferably galactooligosaccharide and FOS), both weight ratios are between 25 to 0.05, more preferably between 20 to 1.Galactooligosaccharide (being preferably β-galactooligosaccharide) more can stimulation of bifidobacteria.Preferably, the described present composition comprises that the degree of polymerization (DP) is that 2 to 10 galactooligosaccharide (being preferably β-galactooligosaccharide) and/or DP are 2 to 60 FOS.
Described galactooligosaccharide is preferably β-galactooligosaccharide.In an especially preferred embodiment, the described present composition comprises β-galactooligosaccharide ([galactolipin] n-glucose; Wherein n is from 2 to 60 integer, namely 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 mainly links together by β key (linkage).β-galactooligosaccharide is also referred to as transgalactooligosac,harides (TOS).For example, β-galactooligosaccharide is with trade mark Vivinal
(TM)(Borculo Domo Ingredients, Netherlands) sells.Another suitable source is Bi2Munno (Classado).Preferably, described TOS comprises based on the β-Isosorbide-5-Nitrae of total key number meter 80% and β-1,6 key at least, more preferably at least 90%.
FOS has DP or average DP is 2 to 250 for comprising, and is preferably 2 to 100, even the NDO of the fructose units chain of 10 to 60 β-connection more preferably.FOS comprises inulin, the polyfructosan of levulan and/or mixed type.A kind of particularly preferred FOS is inulin.The FOS that is suitable for described composition also is commercially available, for example Raftiline
HP (Orafti).Preferably, the average poly-DP of described FOS is greater than 20.
Uronic acid oligosaccharides preferably obtains from pectin degradation product.Therefore to preferably include DP be 2 to 100 pectin degradation product to the described present composition.Preferably, described pectin degradation product prepares from apple pectin, beet pectin and/or citrus pectin.Preferably, described uronic acid oligosaccharides is galactoronic acid oligosaccharides.Preferably, described composition comprise FL and be selected from galactooligosaccharide and uronic acid oligosaccharides in a kind of.
Except 6 '-SL and 3 '-SL, most preferably, described composition comprises β-galactooligosaccharide, FOS and uronic acid oligosaccharides.Find described bond and 6 '-SL and 3 '-SL synergy.β-galactooligosaccharide: FOS: the weight ratio of uronic acid oligosaccharides is preferably (20 to 2): 1:(1 to 20), more preferably (20 to 2): 1:(1 to 10), even more preferably (20 to 2): 1:(1 to 3), even more preferably (12 to 7): 1:(1 to 2).Most preferably, described weight ratio is about 9:1:1.1.
Preferably, the every 100ml of described alimentation composition comprises 100mg (comprise 6 '-SL and 3 '-SL), more preferably 500mg is to 3g, even more preferably every 100ml comprises 800mg to the non-digestibility compound sugar of 2g to the non-digestibility compound sugar of 4g.Based on dry weight basis, described composition preferably comprise 0.5wt% to the non-digestibility compound sugar of 25wt% (comprise 6 '-SL and 3 '-SL), more preferably 1wt% is to 15wt%, in addition more preferably 5wt% to 10wt%.Not too effective aspect the beneficial bacteria of non-digestibility compound sugar in stimulating flora (microbiota) of low amount, however too high amount will cause the side effect of aerogastria and abdominal discomfort.
Alimentation composition
Described alimentation composition is not human milk.Described alimentation composition of the present invention preferably gives in intestines, more preferably oral giving.
Described alimentation composition of the present invention is preferably infant formula.Described alimentation composition of the present invention can be advantageously used for baby's complete nutrition thing.The described present composition preferably comprises lipid components, protein component and carbohydrate component, and the present composition preferably gives with liquid form.The present invention includes dry food, be preferably powder, it is with the explanation about described dry food mixture is mixed with the liquid (being preferably water) that is fit to.
Described alimentation composition of the present invention preferably comprises lipid, protein and digestible carbohydrates, wherein said lipid components provides total caloric 5% to 50%, it is total caloric 5% to 50% that described protein component provides, and described digestible carbohydrates composition provides total caloric 15% to 85%.Advantageously, it is total caloric 20% to 50% that described lipid components provides, and it is total caloric 5% to 30% that described protein component provides, and described digestible carbohydrates composition provides total caloric 30% to 70%.Preferably, it is total caloric 35% to 50% that described lipid components provides, and it is total caloric 7.5% to 12.5% that described protein component provides, and described digestible carbohydrates composition provides total caloric 40% to 55%.Account for total caloric % for calculating described protein component, the gross energy that needs consideration to be provided by described protein, peptide and amino acid.
Described alimentation composition preferably comprises at least a lipid that is selected from animal lipid (except people's lipid) and vegetable lipid.Preferably, the described present composition comprises the bond of vegetable lipid and at least a oil that is selected from fish oil, animal oil, algae oil, fungal oil and bacterium oil.The described present composition preferably includes long-chain polyunsaturated fatty acid (LC-PUFA).LC-PUFA is that length is 20-24 carbon atom, is preferably the aliphatic acid that contains two or more unsaturated bonds or the fatty acyl chain of 20 or 22 carbon atoms.More preferably, the described present composition comprises eicosapentaenoic acid (EPA, n-3), DHA (DHA, n-3) and/or arachidonic acid (ARA, n-6).
Preferably, the described present composition comprises at least 0.1wt% based on the total lipid content meter, preferred 0.25wt% at least, more preferably 0.6wt% at least, even the more preferably LC-PUFA with 20-22 carbon atom of 0.75wt% at least.
Because need as much as possible human milk simulating, LC-PUFA(particularly has the LC-PUFA of 20-22 carbon atom) content, preferably be no more than the 6wt% of total lipid content, more preferably be no more than the 3wt% of total lipid content.Described LC-PUFA can be used as free fatty and provides, and with the triglycerides form, with triglyceride form, with the monoglyceride form, with phospholipid form, or provides as above one or more mixture.The described present composition preferably comprises the 5wt%-75wt% based on total buttermeter, the polyunsaturated fatty acid of preferred 10wt%-50wt%.
Protein in the described alimentation composition preferably is selected from: inhuman animal protein (being preferably lactoprotein), phytoprotein (being preferably soybean protein, pea protein and/or rice protein), its hydrolysate, its free amino acid and composition thereof.Described alimentation composition preferably contains the casein of casein, whey, hydrolysis and/or the lactalbumin of hydrolysis.Preferably, described protein comprises whole protein, more preferably complete milk albumin and/or complete ox casein protein.
Described alimentation composition preferably contains the digestible carbohydrates that is selected from sucrose, lactose, glucose, fructose, corn-syrup solids, starch and maltodextrin, more preferably lactose.
Preferably, described liquid food does not have excessive caloric density, but still provides enough calories with feeding infant.Therefore, described liquid food preferably has the caloric density between 0.1 to 2.5kcal/ml, even the caloric density between 0.5 to 1.5kcal/ml more preferably, most preferably is the caloric density between 0.6 to 0.8kcal/ml.
Preferably, described alimentation composition comprises nucleotides and/or nucleosides, more preferably nucleotides.Preferably, described composition comprises 5'-CMP, 5 '-UMP, AMP, 5'-GMP and/or 5'-IMP, more preferably 5'-CMP, 5 '-UMP, AMP, 5'-GMP and 5'-IMP.Preferably the described composition dry weight of per 100 grams of described composition comprises 5 to 100mg, more preferably 5 arrives 50mg, most preferably 10 to 50mg nucleotides and/or nucleosides.
Baby and child
Described the inventive method can advantageously be applied to the child of 0-36 month human infant, 0-18 month human infant more preferably, 0-12 month human infant more preferably, even 0-6 month human infant more preferably.0-36 month baby comprises the child.In one embodiment, child's age is greater than 6 months to 36 months, or greater than 12 months to 36 months, or greater than 18 months to 36 months.Be down to minimum for the risk that pathogen is caused infection, it is favourable using the ratio preparation infant formula of amount and 6 ' according to 6 '-SL of the present invention-SL and 3 '-SL.Preferably, use amount and 6 ' according to 6 '-SL of the present invention-ratio of SL and 3 '-SL to prepare the infant formula in 1 stage and 2 stages.Preferably, use amount and 6 ' according to 6 '-SL of the present invention-ratio of SL and 3 '-SL to prepare the infant formula in 1 stage.1 stage formulation is used to preferred baby less than 6 months that nutrition is provided, and is preferably preferred baby less than 4 months nutrition is provided.
Embodiment
6 '-SL that embodiment 1 measures in the breast milk
Materials and methods
Serological test
In three days postpartum, the women who passed through hemagglmination collector test determination Lewis blood group the same day of blood sampling.The red blood cell suspension (the 3%-5% red blood cell suspension is in 0.9%NaCl) that use is corresponding and the anti-Lea of monoclonal and anti-Leb antibody (Immucor,
Germany and BAG, Lich, Germany) the inspection hemoagglutination.Incubated at room 15 minutes.Because the difference between serological test and the chromatogram has repeated some blood hemagglutination tests (Thurl et al.1998Milchwissenschaft 53:127-129) 18-25 month postpartum.The women of reception test does not have pregnancy at that time.
Collect sample
All mothers have signed written comment and have agreed to participate in this research, and Ethics Committee of Dresden, Germany university hospital (university hospital of Dresden, Germany) has ratified this research and design.30 Caucasia women lived in the area, Dresden, and they have also given birth to healthy babies at the age at 20 to 35 years old, and described baby is pure breast-feeding during studying.175 whole breast milk samples mainly gather in the following time interval that comprises 7 main dates: the 3rd day, and 2-5 days postpartum; The 8th day, d6-d9; The 15th day, d13-d18; The 22nd day, d20-d26; The 30th day, d28-d33; The 60th day, d57-d65; The 90th day, d88-d96.If the motherhood has collected unnecessary one the newborn sample corresponding to the above-mentioned time interval, so all samples are analyzed with the arithmetic mean of instantaneous value of concentration of oligosaccharide.In once to the preliminary examination from 6 regional Caucasia women of Frankfurt, Germany (Frankfurt/Main), in two 24 hours periods in the 7th day postpartum and the 60th day, the inventor does not find that any obvious compound sugar changes (data are unlisted).Yet even in order to get rid of very little daylight effect, the sampling time in this research is fixed on when feeding the morning.(mid-feed) Sampling techniques were collected during the use that 6-10 is ordered in the morning usually of described newborn sample was fed the time in the morning, and this technology was proved to be a kind of suitable Sampling techniques for carbohydrate analysis in the past.Aliquot sample in the centre of feeding with about 5-10ml is extruded in the plastic containers by hand.With newborn sample immediately freezing and be stored in-20 ℃ lower until analyze.
The chromatography of compound sugar
The sample preparation comprises the gel permeation chromatography purifying, and carries out HPAEC by the method for having described (Thurl et al.1996Anal Biochem.235:202-206) and analyze.In simple terms, the human milk sample was heated 30 minutes under 70 ℃.In the 1ml human milk, add 0.1ml and contain internal standard compound stachyose and galacturonic aqueous acid.Then described sample is centrifugal and ultrafiltration (Millipore Centrifree, 30kDa holds back).Use Toyopearl HW 40 (S) post (1,6x 80cmTosoHaas, Stuttgart, Germany) by gel permeation chromatography described protein and lipopenic sample classification to be separated into lactose, neutral compound sugar and acidic oligomer sugar.The carbohydrate fraction is washed with water (flow velocity 1ml/min) and detect by refractive index and monitor.Lactose fraction is abandoned; Neutral and acidic fraction is analyzed with HPAEC-PED.The elution requirement of acidic oligomer sugar 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 manually hydrolytic degradation to responsive especially sialylated compound sugar, free N-acetyl-neuraminate (Neu5Ac) is quantitative with acidic oligomer sugar.Neu5Ac relative concentration constant (mean concentration is 0.019g/L in the ursing mother of Lewis blood group Le (a-b+)).The amount of free NeuAc with reported on the same order of magnitude, and correspond respectively to the NeuAc of about 2% and 4% compound sugar combination when lactation begins and after three months.Therefore, can get rid of the obvious degradation to acidic oligomer sugar that is caused by sialidase effect or heat treated.
Statistical analysis
Data by the statistical method analysis are comprised of single concentration of oligosaccharide or are comprised of the concentration of the summation of different carbohydrate.Except total neutral compound sugar and total acidic oligomer sugar, following total nuclear structure and the carbohydrate of fructose are added up to respectively: nuclear Lac=Lac+3-FL+2 '-FL+LDFT+3 '-SL+6 '-SL; Nuclear LNT=LNT+LNFP I+LNFP II+LNDFH I+LNDFH II+LSTa+LSTb+DSLNT; Nuclear LNnT=LNnT+LNFP III+LSTc; Nuclear 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+LNDFHII; Fuc α 1-3GlcNAc=LNFP III+3 '-F-LNH+2 ', 3 '-DF-LNH.
Data set is respectively three breast milk groups and seven times of nursing by two factor tissues.In addition, because different sample sizes, data set is very uneven.In breast milk group 1 (ursing mother that Lewis blood group Le (a-b+) is arranged) altogether 109 samples be assigned in the time of 10 to 21 sample ranges, yet in the 2nd group (the non-ursing mother that Lewis blood group Le (a+b-) is arranged; 28 samples) time of nursing is represented by 3-5 sample, (the ursing mother that Lewis blood group Le (a-b-) is arranged in the 3rd group; 17 samples) by 2-3 sample representative.Therefore, used the several method of analyzing concentration of oligosaccharide mean value.In the 1st group of situation, at first use one-way analysis of variance (ANOVA) then to check the mean value of comparison time of nursing with Student-Newman-Keuls.Two factor ANOVA of use III type quadratic sum are used to the mean value of three breast milk groups of comparison, then calculate the least square average.Therefore, each cell mean does not depart from and can compare together fully.The difference of mean value is checked in 5% significance with the Tukey-Kramer method.In whole two variate models, every group of concentration of specimens difference with the participation women of each time produces experimental error.Usually, be alterable height from concentration of oligosaccharide in the same breast milk group women's of given time of nursing the breast milk.Because these huge interindividual variations, although notable difference is arranged on the surface, in same situation, there is not significant difference (P〉5%) between the average.
Simulated concentration of oligosaccharide trend between lactation with regression analysis.Carried out match and the check that simple linear regression and secondary and cubic polynomial return in remarkable regression coefficient.If regression coefficient is (P＜5%) then accept this model significantly.All regression analyses are carried out with independent numerical value.All calculate and use the SAS system to finish (SAS Institute Inc.2002-2003SAS/STATrelease9.1SAS Institute Inc., Cary, NC, USA).
The result
The carbohydrate fraction
The acidic oligomer sugar of six kinds of main non-fucosylations as shown in table 1,3 '-SL, 6 '-SL, LSTa, LSTb, LSTc, DSLNT can measure by chromatograph.The approximate sugared fraction of the acidic oligomer in the human milk that represented of these carbohydrate summations.Because the importance of Lewis blood group system, these sugar are also checked respectively according to described three breast milk groups.The newborn sample of all three kinds of newborn types demonstrates aforesaid six kinds of acidic oligomer sugar.The amount of described acidic oligomer sugar fraction does not have significant difference in three breast milk groups.In addition, all breast milk groups have shown about three times of declines of similar acid sugar concentration during studying.
The structure of the acid newborn compound sugar that table 1. was measured in should studying
3 '-SL, 3 '-sialylated lactose; 6 '-SL, 6 '-sialylated lactose; LSTa-c, sialylated lactose-N-tetrose a-c (Sialyllacto-N-tetraoses a-c); DSLNT, two sialylated lactose-N-tetrose (Disialyllacto-N-tetraose).
Acidic saliva acidifying compound sugar
The mean concentration of described six kinds of acidic oligomer sugar of measuring in this research is presented in the table 2.Quantitatively 6 '-SL is the most important acid carbohydrate in present all Ruzhongs.Detected 3 '-SL, LSTc and the DSLNT of moderate quatity, yet the concentration level of LSTa and LSTb is no more than 0.1g/L.The independent mean concentration of acid sugar, although not identical statistically in some cases, in three breast milk groups, change to a great extent, thereby confirmed result about whole carbohydrate fraction.
Similarly, be presented at the similar trend of time effect and other breast milk groups (data are unlisted) of breast milk group 1 in the table 2.The concentration of 6 '-SL reaches peak value in the 8th day transitional period breast milk, until minute the 90th a day puerperium has descended at least 3 times.LSTc also contains Neu5Ac α 2-6Gal-key, has descended in a similar fashion about 5 times during studying.3 '-SL after the 1st stage of lactation obviously descends, in ripe breast milk with relatively constant horizontal expression.LSTa has the less important acid sugar of Neu5Ac α 2-3Gal-key, and its concentration descended in one week of postpartum, to such an extent as to do not detect in the several breast milk samples after month.By contrast, the concentration that has a LSTb of Neu5Ac α 2-6GlcNAc-key in first month, increase and after keep relatively constant.DSLNT, the unique two sialylated carbohydrate of analyzing, a kind of mixed structure between LSTa and LSTb demonstrates the highest time graph.
Table 2. acidic oligomer sugar
1)Concentration (g/L)
1) there is the average of same letter obviously not different; The Student-Newman-Keuls check is used for group 1 interior comparison, and the Tukey-Kramer check is used 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 is measured do not demonstrate great difference in three breast milk groups.This is not unexpected because these sugar lack the fucose part.Main acid sugar in this research, the concentration of 6 '-SL exceed at least twice of the amount reported from other groups, however the relative concentration of DSLNT lower (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 the people such as the amount of 3 '-SL, LST a, LSTb and LSTc and Asakuma detect is lower than the concentration that the people such as Coppa report in approximate extents, be higher than the numerical value that the people such as Bao find.Although the quantitative result from difference research (comprising this research) has shown huge difference, in the lactation first month, usually all found the obvious decline of the whole and most of independent sugar of acid sugar fraction.
6 '-SL and LSTc descend in a similar manner, and the following hypothesis of this true support: single sialyltransferase may be ST6Gall, and 2 type structures of unique acceptance participate in the biosynthesis of these carbohydrate.Descending more significantly of LSTc can be with the precursor of LSTc---the amount of the decline explanation of nuclear LNnT, yet the precursor of 6 '-SL---lactose keeps constant after one week of postpartum.3 '-SL that little degree descends during the research can be by ST3Gal IV or synthetic (the two kinds of α 2 of ST3Gal VI, the 3-sialyltransferase, preferentially 2 type structures are worked), and it is very many that the inventor finds that less important acid sugar LSTa descends, 2 and 3 months after can not or can only partly detect.The inventor guess preferentially to 1 type structure work 2,3-sialyltransferase ST3Gall III participates in the biosynthesis of LSTa and DSLNT.LSTb is the unique acid sugar that increases in the first month in postpartum, the result before this has confirmed.So-called ST6GlcNAc can shift sialic acid part to the GlcNAc of near-end, produce one kind of LSTb and DSLNT(and show α 2,6-connect with α 2, the compound sugar of the neuraminic acid that 3-connects).
Embodiment 2 infant formulas
The every 100ml(dry weight of infant formula 13.9g) comprise:
1.4g protein (whey and casein)
7.3g digestible carbohydrates (comprising lactose)
3.6g fat (vegetablefats, fish oil)
1.03g non-digestibility compound sugar wherein has 120mg 6 '-SL, 30mg 3 '-SL, 80mg 2FL, 720mg β-galactooligosaccharide and 80mg FOS
Further comprise: choline, inositol, taurine, mineral matter, trace element and vitamin known in the art.
Embodiment 3 child's dairy compositions
The every 100ml(67kcal of child's dairy compositions (be 1-3 year baby design); Dry weight 15.1g) comprising:
1.5g protein (lactalbumin/casein 1/1w/w)
8.5g digestible carbohydrates (6.0g lactose, 1.1g maltodextrin are wherein arranged)
3.0g fat (vegetablefats)
1.23g non-digestibility compound sugar wherein has 120mg 6 '-SL, 30mg 3 '-SL, 80mg 2FL, 900mg β-galactooligosaccharide and 100mg FOS
Mineral matter, trace element, vitamin known in the art, comprise choline and taurine.
Claims (12)
1. one kind comprises 6 '-sialylated lactose (6 '-SL) composition is for the preparation of the purposes that the alimentation composition of nutrition is provided for the baby, and described alimentation composition comprises at least 1g/L 6 '-SL, and wherein the ratio of 6 '-SL:3 '-SL is higher than 2.
2. according to claim 1 purposes, the concentration of wherein said 6 '-SL is at least 1.1g/L.
3. according to claim 1 and 2 purposes, the ratio of wherein said 6 '-SL:3 '-SL is higher than 3.
4. according to each purposes of aforementioned claim, the ratio of wherein said 6 '-SL:3 '-SL is higher than 4.
5. according to each purposes of aforementioned claim, wherein said alimentation composition further comprises the non-digestibility compound sugar that is selected from FOS and galactooligosaccharide.
6. according to each purposes of aforementioned claim, wherein said alimentation composition further comprises the uronic acid oligosaccharides that is selected from galactoronic acid oligosaccharides and pectin degradation product.
7. according to each purposes of aforementioned claim, wherein said composition comprises the lipid that total caloric 35%-50% is provided, and the protein of total caloric 7.5%-12.5% is provided, and the digestibility carbohydrate that total caloric 40%-55% is provided.
8. according to each purposes of aforementioned claim, wherein said alimentation composition is used for providing nutrition to 0-36 month baby.
9. according to each purposes of aforementioned claim, wherein said alimentation composition is used for providing nutrition to 0-6 month baby.
10. alimentation composition, comprise total caloric 35%-50% fat is provided, total caloric 7.5%-12.5% protein is provided, and provide total caloric 40%-55% digestibility carbohydrate, and further comprise 6 ' of 1-3g/L-SL, wherein the ratio of 6 '-SL:3 '-SL is between 2.5 to 5.5.
11. alimentation composition according to claim 10 further comprises β-galactooligosaccharide, FOS and uronic acid oligosaccharides.
12. according to claim 10 or 11 alimentation composition, it is 1 stage infant formula.
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| CN109890222A (en) * | 2016-10-14 | 2019-06-14 | Mjn 美国控股有限责任公司 | Personalized formulation product comprising human milk oligosaccharides |
| CN111447845A (en) * | 2017-12-08 | 2020-07-24 | 詹尼温生物技术有限责任公司 | Spray dried sialyllactose |
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| WO2012092156A1 (en) | 2010-12-31 | 2012-07-05 | Abbott Laboratories | Methods for decreasing the incidence of necrotizing enterocolitis in infants, toddlers, or children using human milk oligosaccharides |
| MY192208A (en) | 2010-12-31 | 2022-08-08 | Abbott Lab | Nutritional formulations including human milk oligosaccharides and antioxidants and uses thereof |
| 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 |
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- 2011-04-27 CN CN2011800210644A patent/CN102858191A/en active Pending
- 2011-04-27 CN CN201610421321.8A patent/CN106072654A/en active Pending
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| CN109890222A (en) * | 2016-10-14 | 2019-06-14 | Mjn 美国控股有限责任公司 | Personalized formulation product comprising human milk oligosaccharides |
| CN111447845A (en) * | 2017-12-08 | 2020-07-24 | 詹尼温生物技术有限责任公司 | Spray dried sialyllactose |
| US11582994B2 (en) | 2017-12-08 | 2023-02-21 | Chr. Hansen HMO GmbH | Spray-dried 3-fucosyllactose |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2011136647A1 (en) | 2011-11-03 |
| EP2563165A1 (en) | 2013-03-06 |
| CN106072654A (en) | 2016-11-09 |
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