CN115316660A - Nutritional composition, food product comprising the same and use of the nutritional composition - Google Patents
Nutritional composition, food product comprising the same and use of the nutritional composition Download PDFInfo
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- CN115316660A CN115316660A CN202211056371.2A CN202211056371A CN115316660A CN 115316660 A CN115316660 A CN 115316660A CN 202211056371 A CN202211056371 A CN 202211056371A CN 115316660 A CN115316660 A CN 115316660A
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- nutritional composition
- osteopontin
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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
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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
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/115—Fatty acids or derivatives thereof; Fats or oils
- A23L33/12—Fatty acids or derivatives thereof
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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
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- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
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Abstract
The present invention relates to a nutritional composition, a food product comprising the same and uses of the nutritional composition. The nutritional composition comprises: 2 '-fucosyllactose (2' -FL), docosahexaenoic acid (DHA), and Osteopontin (OPN). The nutritional composition may optionally further comprise: a carbohydrate selected from yeast beta-glucan and/or polydextrose; and/or a peptide or amino acid selected from casein phosphopeptide (CPP) and/or L-cystine and/or L-phenylalanine; and/or a vitamin selected from pantothenic acid and/or biotin; and/or a mineral selected from sodium citrate and/or potassium chloride. The nutritional composition is capable of enhancing brain development and intelligence in infants and infants, and in particular promoting neurological development such as promoting neuronal maturation, synaptogenesis and/or myelination.
Description
Technical Field
The present invention generally relates to the field of food products. In particular, the invention relates to a nutritional composition for improving brain development and intelligence, in particular promoting neural development such as neuronal maturation, synaptogenesis and/or myelination in infants, a food comprising the nutritional composition, and uses of the nutritional composition. More specifically, the present invention relates to a nutritional composition comprising 2 '-fucosyllactose (2' -FL), osteopontin (OPN) and docosahexaenoic acid (DHA), to a food product comprising the nutritional composition, and to the use of the nutritional composition for the non-therapeutic purpose of improving brain development and intelligence, in particular promoting neurological development in infants.
Background
Oligodendrocyte Precursor Cells (OPCs) were first discovered in 1993 by Raff, miller, et al, and have been extensively studied. Both the developing and mature central nervous system contain oligodendrocyte precursor cells. Myelin constituting cells in the central nervous system, derived from oligodendrocyte precursor cells. The types of myelin proteins expressed by OLs, such as myelin-associated glycoprotein (MAG) and myelin-binding protein (MBP), are associated with their maturation phase. Myelinated OLs express MAG, with the expression of MAG increasing during maturation of the OLs. MAG is a sialic acid-binding immunoglobulin-like lectin that is expressed predominantly in the periaxonal region of myelin, although it accounts for a small fraction of the total protein content of myelin. It appears to play an important role in oligodendrocyte-axon interactions and mediates bidirectional signaling between axons and OLs to support myelination. MBP is strongly expressed in mature myelinated OLs and is one of the major components of myelin. MBP appears to play a positive role in myelination and compaction. In fact, MBP is polymerizing and forming a network of viscous reticulins, which is critical for the hopping current.
The development of the brain is influenced by genetic and environmental factors. In the latter, maternal and early-life nutrition plays a key role in promoting neuronal development, such as neuronal maturation, synaptogenesis and/or myelination. Myelination is a process by which Oligodendrocytes (OLs) of the Central Nervous System (CNS) form myelin sheaths around axons, which is critical for normal brain connections. In humans, myelination begins in the middle of gestation and peaks in the first few years of life. Environmental factors may influence myelination during human brain development. In particular, different nutritional components appear to have different effects on myelination, suggesting that early life nutrition may be an important factor in regulating myelination.
During development of the central nervous system, oligodendrocyte Precursor Cells (OPCs) migrate from within the cortex and produce an adult population of Oligodendrocytes (OLs). Post-mitotic OPCs differentiate into myelinated OLs, which extend many processes, establishing contact with axons of different neurons, initiating myelination, a process that enhances neuronal connectivity and supports the maturation of neonatal cognitive function.
In the central nervous system, each step of myelination, including proliferation of OPCs, differentiation and maturation of OPCs into myelinated OLs, and myelination, is highly regulated by both external and internal factors. In particular, different nutrients have different effects on myelination, suggesting that early life nutrition may have important implications for the regulation of myelination. Therefore, identification of early life nutritional factors that support myelination is critical for optimal brain and cognitive development.
It would be desirable to provide a composition that enhances brain development and intelligence in infants, and in particular promotes neural development, e.g., promotes neuronal maturation, synaptogenesis, and/or myelination.
Disclosure of Invention
It is an object of the present invention to provide a nutritional composition for use in improving brain development and intelligence, in particular promoting neurological development such as neuronal maturation, synaptogenesis and/or myelination in infants and young children.
It is another object of the present invention to provide a food product comprising the nutritional composition.
It is another object of the present invention to provide the use of said nutritional composition for non-therapeutic purposes (nutrition and health) in improving brain development and intelligence, especially in promoting neurological development in infants and young children.
The present inventors have found that when Osteopontin (OPN) and 2 '-fucosyllactose (2' -FL) are used in combination, they can synergistically promote the promotion of neuronal development such as neuronal maturation, synaptogenesis and/or myelination, and in particular can synergistically promote the proliferation, maturation and/or differentiation of OPCs into mature OLs and/or myelinating properties of OLs; when further used in combination with docosahexaenoic acid (DHA), it is capable of further promoting, e.g., synergistically promoting, neural development such as neuronal maturation, synaptogenesis and/or myelination, particularly promoting the proliferation, maturation and/or differentiation of OPCs into mature OLs and/or the myelinating properties of OLs.
In particular, the present invention is realized by:
1. a nutritional composition comprising 2 '-fucosyllactose (2' -FL), docosahexaenoic acid (DHA), and Osteopontin (OPN).
2. The nutritional composition of item 1, consisting of 2 '-fucosyllactose (2' -FL), docosahexaenoic acid (DHA), and Osteopontin (OPN).
3. The nutritional composition according to any of the items 1-2, wherein the 2' -fucosyllactose is provided in the form of a natural source, and/or a synthetic source, and/or a bacterial fermentation source.
4. The nutritional composition according to any one of items 1-3, wherein osteopontin is provided in the form of: osteopontin protein powder, and/or osteopontin-containing whey powder.
5. The nutritional composition of any one of items 1-4, wherein:
the mass ratio of 2 '-fucosyllactose (2' -FL) to osteopontin in the nutritional composition is from 0.05 to 2000, preferably from 0.1 to 1000, and 1, preferably from 1 to 1000
The mass ratio of docosahexaenoic acid (DHA) to osteopontin in the nutritional composition is 0.02-1000, preferably 0.05-500;
preferably, the mass ratio of 2 '-fucosyllactose (2' -FL), docosahexaenoic acid (DHA) to osteopontin in the nutritional composition is 0.05-2000.
6. The nutritional composition of any one of items 1-5, further comprising:
-a carbohydrate selected from yeast beta-glucan and/or polydextrose; and/or
-a peptide or amino acid selected from casein phosphopeptide (CPP) and/or L-cystine and/or L-phenylalanine; and/or
-vitamins selected from pantothenic acid and/or biotin; and/or
-minerals selected from sodium citrate and/or potassium chloride;
preferably, the mass ratio of yeast β -glucan, when present, to osteopontin is from 0.0025 to 625, preferably from 0.1 to 15;
preferably, when polydextrose is present, the mass ratio to osteopontin is from 0.05 to 10000, preferably from 3.5 to 2000,
preferably, when casein phosphopeptide (CPP) is present, the mass ratio thereof to osteopontin is 0.025 to 500, preferably 0.025 to 55,
preferably, the mass ratio of L-cystine, when present, to osteopontin is from 0.025 to 200, preferably from 0.05 to 25,
preferably, the mass ratio of L-phenylalanine to osteopontin, when present, is from 0.005 to 200, preferably from 0.025 to 20,
preferably, when pantothenic acid is present, its mass ratio to osteopontin is from 0.0025 to 25, preferably from 0.025 to 2.5,
preferably, when biotin is present, its mass ratio to osteopontin is 0.0000025 to 0.025,
preferably, the mass ratio of sodium citrate, when present, to osteopontin is from 0.05 to 2000, preferably from 0.75 to 100,
preferably, when potassium chloride is present, its mass ratio to osteopontin is from 0.05 to 2000, preferably from 0.75 to 100.
7. A food product comprising the nutritional composition according to any one of items 1-6.
8. The food product of item 7, wherein the food product is in powder or liquid form.
9. The food product of items 7-8, which is an infant formula such as an infant formula, a follow-on formula, a baby formula such as an infant formula, e.g. an infant formula, a baby formula; supplementary food for infants; a nutritional or dietary supplement; or pregnant woman concocting milk powder.
10. The food product according to any one of the items 7-9, wherein the nutritional composition is added in an amount such that the weight content of 2' -fucosyllactose is at least 0.01%, preferably at least 0.02%, preferably at least 0.03%, preferably at least 0.04% and at most 10.0%, preferably at most 8.0%, preferably at most 5.0%, preferably at most 4.0%, relative to the total weight of the food product, the weight content of osteopontin is at least 0.001%, preferably at least 0.002%, preferably at least 0.003%, preferably at least 0.004% and at most 1.0%, preferably at most 0.8%, preferably at most 0.5%, preferably at most 0.4%, the weight content of docosahexaenoic acid is at least 0.005%, preferably at least 0.01%, preferably at least 0.02% and at most 5.0%, preferably at most 4.0%, preferably at most 2.0%; preferably, the weight content of 2 '-fucosyllactose (2' -FL) is 0.04-4%, the weight content of docosahexaenoic acid is 0.02-2.0%, and the weight content of osteopontin is 0.004-0.4%.
11. The food product of any of clauses 7-10, wherein:
-when yeast β -glucan is present in the nutritional composition, the nutritional composition is added in an amount such that the weight content of yeast β -glucan in the food product is 0.001-2.5% relative to the total weight of the food product; and/or
-when polydextrose is present in the nutritional composition, the nutritional composition is added in an amount such that the polydextrose content in the food product is comprised between 0.02 and 40% by weight relative to the total weight of the food product; and/or
-when casein phosphopeptide (CPP) is present in the nutritional composition, the nutritional composition is added in an amount such that the casein phosphopeptide (CPP) content in the food product is between 0.01 and 2% by weight relative to the total weight of the food product; and/or
-when L-cystine is present in the nutritional composition, the nutritional composition is added in an amount such that the content by weight of L-cystine in the food product is between 0.01 and 0.8% relative to the total weight of the food product; and/or
-when L-phenylalanine is present in the nutritional composition, the nutritional composition is added in an amount such that the content by weight of L-phenylalanine in the food product is between 0.002 and 0.8% relative to the total weight of the food product; and/or
-when pantothenic acid is present in the nutritional composition, the nutritional composition is added in an amount such that the pantothenic acid content in the food is from 0.001% to 0.1% by weight, relative to the total weight of the food; and/or
-when biotin is present in the nutritional composition, the nutritional composition is added in an amount such that the content by weight of biotin in the food product is between 0.000001% and 0.0001% with respect to the total weight of the food product; and/or
-when sodium citrate is present in the nutritional composition, the nutritional composition is added in an amount such that the sodium citrate is present in the food product in an amount of 0.02-8% by weight relative to the total weight of the food product; and/or
-when potassium chloride is present in the nutritional composition, the nutritional composition is added in an amount such that the potassium chloride content in the food product is 0.02-8% by weight relative to the total weight of the food product.
12. Use of a nutritional composition according to any of items 1-6 or a food product according to any of items 7-11 for non-therapeutic purposes in improving brain development and intelligence, in particular promoting neurological development, in an infant.
Drawings
Figure 1 shows the effect of different nutritional composition samples on neural cells after 12d in vitro culture-A2B 5 immunostaining pattern (green). Scale bar 50 μm.
FIG. 2 shows the effect of different nutritional composition samples on neural cells after 18d in vitro culture-MAG immunostaining (green). Scale bar 50 μm.
Figure 3 shows the effect of different nutritional composition samples on neural cells after 30d in vitro culture-MBP immunostaining (green). Scale bar 50 μm.
Detailed Description
Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art, but in case of conflict, the definitions in this specification shall control.
As used herein, the following terms have the following meanings.
The term "infant" refers to a person of 0 to 6 months of age.
The term "older infant" refers to a person 6 to 12 months of age.
The term "young child" refers to a person of 12 to 36 months of age.
The term "infant" refers to a person 0-36 months of age.
The term "infant formula" as used herein encompasses infant formulas, follow-up infant formulas and toddler formulas. Typically, infant formulas are used as a substitute for breast milk from the birth of the infant, larger infant formulas are used as a substitute for breast milk from the 6-12 months after the birth of the infant, and infant formulas are used as a substitute for breast milk from the 12-36 months after the birth of the infant.
The term "infant formula" refers to a liquid or powder product made by adding appropriate amounts of vitamins, minerals and/or other ingredients to milk and milk protein products or soy and soy protein products as the main raw materials and producing and processing only by physical methods. Is suitable for normal infants, and the energy and nutrient components of the infant formula can meet the normal nutritional requirements of the infants of 0-6 months.
The term "follow-up infant formula" refers to a liquid or powder product made by adding appropriate amounts of vitamins, minerals and/or other ingredients to milk and milk protein products or soy and soy protein products as the main raw materials and producing and processing by physical methods only. Is suitable for older infants, and has energy and nutritional components capable of meeting partial nutritional requirements of older infants of 6-12 months.
The term "infant formula" refers to a liquid or powder product prepared by using milk and milk protein products or soybean and soybean protein products as main raw materials, adding appropriate amount of vitamins, minerals and/or other components, and producing and processing by a physical method. Is suitable for children, and has energy and nutritional components capable of meeting partial nutritional requirements of normal children of 12-36 months.
The term "breast milk" is understood to mean the mother's breast milk or colostrum.
The term "fully breastfed infant or young child" has the usual meaning and refers to an infant in which the majority of the nutrients and/or energy are derived from human breast milk.
The term "infant/follow-on/older infant/toddler fed primarily with infant formula" has the usual meaning and refers to an infant or toddler whose source of nutrients and/or energy originates primarily from physically processed infant formula, follow-on milk or growing up milk. The term "primarily" refers to at least 50%, such as at least 75%, of those nutrients and/or energies.
Furthermore, in the context of the present invention, the term "comprising" or "comprises" does not exclude other possible elements. The compositions of the present invention (including the various embodiments described herein) may comprise, consist of, or consist essentially of the following elements: essential elements and necessary limitations of the invention described herein, as well as any other or optional ingredients, components or limitations described herein or otherwise required.
The subject of the invention is suitable for normal humans, and may be infants and/or older infants, and/or young children, and/or young adults, and/or middle aged adults, and/or elderly. More preferred are formula fed human infants.
All percentages are by weight unless otherwise indicated.
The invention will now be described in more detail. It should be noted that the various aspects, features, embodiments, examples, and advantages thereof described herein may be compatible and/or may be combined together.
The present invention relates to a nutritional composition for improving brain development and intelligence, in particular for promoting neuronal development, synaptogenesis and/or myelination, in infants, to a food product comprising the nutritional composition, and to the use of the nutritional composition for non-therapeutic purposes in improving brain development and intelligence, in particular for promoting nerve development, in infants.
The present invention will be specifically described below.
Nutritional composition
In one aspect, the present invention provides a nutritional composition comprising 2 '-fucosyllactose (2' -FL), docosahexaenoic acid (DHA), and Osteopontin (OPN).
2 '-fucosyllactose (2' -FL) is a neutral trisaccharide consisting of L-fucose, D-galactose and D-glucose units, in which the monosaccharide L-fucose is linked to the disaccharide D-lactose via an alpha (1 → 2) linkage. The molecular formula is C 18 H 31 O 15 The molecular weight is 488.439g/mol, and the molecular structure is as follows.
Osteopontin (OPN) is an O-glycosylated phosphoprotein, classified as an extracellular matrix protein. Structurally, OPN contains a specific RGD (arginine-glycine-aspartic acid, arg-Glu-Asp) sequence. OPN was originally thought to be an important bone matrix protein, closely related to bone formation and development. It has important physiological effects in immune activation, wound repair, blood vessel regeneration, and bone remodeling.
Docosahexaenoic acid (DHA) refers to cis-4, 7,10,13,16, 19-docosahexaenoic acid, which is a straight chain fatty acid containing 22 carbon atoms and 6 carbon-carbon double bonds, and has a molecular formula of C 22 H 32 O 2 。
The present inventors have surprisingly found that when 2 '-fucosyllactose (2' -FL), and Osteopontin (OPN) are used in combination, they are capable of synergistically promoting neural development such as promotion of neuronal maturation, synaptogenesis, and/or myelination, and in particular may synergistically promote the proliferation, maturation, and/or differentiation of OPCs into mature OLs and/or the myelinating properties of OLs. When 2 '-fucosyllactose (2' -FL) and Osteopontin (OPN) are further used in combination with docosahexaenoic acid (DHA), it is possible to further promote, for example, synergistically promote the neural development such as neuronal maturation, synaptogenesis and/or myelination, in particular the myelination properties of OPC, for example, proliferation, maturation and/or differentiation into mature OLs and/or OLs.
In one embodiment, the nutritional composition consists of 2 '-fucosyllactose (2' -FL), docosahexaenoic acid (DHA), and Osteopontin (OPN).
In one embodiment, osteopontin may be provided in or may be derived from the following form: osteopontin protein powder, and/or osteopontin-containing whey powder. The osteopontin content of the osteopontin protein powder may be generally 30 to 99% by weight. The osteopontin content of the osteopontin-containing whey powder may be generally 2 to 30% by weight.
In one embodiment, 2 '-fucosyllactose (2' -FL) can be provided as a source as follows: natural sources, and/or synthetic sources, and/or bacterial fermentation sources. The 2' -fucosyllactose content in each source can typically be 60-99.9%.
1-1 970.
1-1 900.
In one embodiment, the mass ratio of 2 '-fucosyllactose (2' -FL), docosahexaenoic acid (DHA) to Osteopontin (OPN) in the nutritional composition may be from 0.05 to 2000.
When the mass ratio of 2 '-fucosyllactose (2' -FL), docosahexaenoic acid (DHA) and osteopontin in the nutritional composition is within the above-mentioned range, neurodevelopmental e.g. neuronal maturation, synaptogenesis and/or myelination can be promoted more significantly, e.g. synergistically, in particular to promote the proliferation, maturation and/or differentiation of OPCs into mature OLs and/or myelinating properties of OLs.
In one embodiment, the nutritional composition may optionally further comprise, in addition to 2 '-fucosyllactose (2' -FL), osteopontin, and docosahexaenoic acid (DHA), the following:
-a carbohydrate selected from yeast beta-glucan and/or polydextrose; and/or
-a peptide or amino acid selected from casein phosphopeptide (CPP) and/or L-cystine and/or L-phenylalanine; and/or
-vitamins selected from pantothenic acid and/or biotin; and/or
-minerals selected from sodium citrate and/or potassium chloride.
In one embodiment, the nutritional composition may consist of:
(1) 2 '-fucosyllactose (2' -FL);
(2) Osteopontin;
(3) Docosahexaenoic acid (DHA); and
(4) One or more of the following:
-a carbohydrate selected from yeast beta-glucan and/or polydextrose; and/or
-a peptide or amino acid selected from casein phosphopeptide (CPP) and/or L-cystine and/or L-phenylalanine; and/or
-vitamins selected from pantothenic acid and/or biotin; and/or
-minerals selected from sodium citrate and/or potassium chloride.
In one embodiment, the nutritional composition comprises yeast beta glucan and/or polydextrose. That is, the nutritional composition may include yeast beta glucan, or polydextrose, or both yeast beta glucan and polydextrose.
1, in the following description, the following.
1, 1.50 7500.
In one embodiment, the nutritional composition comprises casein phosphopeptide (CPP) and/or L-cystine and/or L-phenylalanine. That is, the nutritional composition may include casein phosphopeptide (CPP), or L-cystine, or L-phenylalanine, or both casein phosphopeptide (CPP) and L-cystine, or both casein phosphopeptide (CPP) and L-phenylalanine, or both L-cystine and L-phenylalanine, or both casein phosphopeptide (CPP) and L-cystine and L-phenylalanine.
A.
1.5.
1.1, 0.70.
In one embodiment, the nutritional composition may include pantothenic acid and/or biotin. That is, the nutritional composition may include pantothenic acid, or biotin, or both pantothenic acid and biotin.
In one embodiment, the ratio of.
In one embodiment, the mass ratio of biotin to osteopontin can be in the range of 0.0000025 to 0.025, preferably 0.0000125 to 0.0125, such as 0.0000025, 0.000005 to 1, 0.000010, 1, 0.00002.
In one embodiment, the nutritional composition may include sodium citrate and/or potassium chloride. That is, the nutritional composition may include sodium citrate, or potassium chloride, or both sodium citrate and potassium chloride.
In one embodiment, when sodium citrate is present, its mass ratio to osteopontin may be from 0.05 to 2000, preferably from 0.75 to 100, 1.1.
In one embodiment, when potassium chloride is present, its mass ratio to osteopontin may be 0.05 to 2000, preferably 0.75 to 100, 1.1.
The inventors have found that when the above optional substances are included in the nutritional composition in addition to 2 '-fucosyllactose (2' -FL), osteopontin and docosahexaenoic acid (DHA), especially when the mass ratio of the optional substances to osteopontin is within the above range, it is possible to more significantly promote the promotion of neural development such as neuronal maturation, synaptogenesis and/or myelination, for example, the promotion of the proliferation, maturation and/or differentiation of OPCs into mature OLs and/or myelinating properties of OLs.
Food product
In another aspect, the invention also relates to a food product comprising the nutritional composition.
The food product of the invention may be in powder form or in liquid form.
The food product of the invention may be an infant formula (e.g. infant formula, follow-up formula, baby formula) such as an infant formula (e.g. infant formula, baby formula), an infant formula, a nutritional or dietary supplement, or a pregnant woman formula.
In one embodiment, the nutritional composition is added in an amount such that the weight content of 2 '-fucosyllactose (2' -FL) is at least 0.01%, preferably at least 0.02%, preferably at least 0.03%, preferably at least 0.04% and at most 10.0%, preferably at most 8.0%, preferably at most 5.0%, preferably at most 4.0%, relative to the total weight of the food product. <xnotran> , ,2'- (2' -FL) 0.01%, 0.02%, 0.03%, 0.04%, 0.05%, 0.06%, 0.07%, 0.08%, 0.09%, 0.10%, 0.15%, 0.20%, 0.25%, 0.30%, 0.35%, 0.40%, 0.45%, 0.50%, 0.55%, 0.60%, 0.65%, 0.70%, 0.75%, 0.80%, 0.85%, 0.90%, 0.95%, 1.00%, 1.05%, 1.10%, 1.15%, 1.20%, 1.25%, 1.30%, 1.35%, 1.40%, 1.45%, 1.50%, 1.55%, 1.60%, 1.65%, 1.70%, 1.75%, 1.80%, 1.85%, 1.90%, 1.95%, 2.00%, 2.05%, 2.10%, 2.15%, 2.20%, 2.25%, 2.30%, 2.35%, 2.40%, 2.45%, 2.50%, 2.55%, 2.60%, 2.65%, 2.70%, 2.75%, 2.80%, 2.85%, 2.90%, 2.95%, 3.00%, 3.05%, 3.10%, 3.15%, 3.20%, 3.25%, 3.30%, 3.35%, 3.40%, 3.45%, 3.50%, 3.55%, 3.60%, 3.65%, 3.70%, 3.75%, 3.80%, 3.85%, 3.90%, 3.95%, 4.00%, 4.05%, 4.10%, 4.15%, 4.20%, 4.25%, 4.30%, 4.35%, 4.40%, 4.45%, 4.50%, 4.55%, 4.60%, 4.65%, 4.70%, 4.75%, 4.80%, 4.85%, 4.90%, 4.95%, 5.00%, 5.05%, 5.10%, 5.15%, 5.20%, 5.25%, 5.30%, 5.35%, 5.40%, 5.45%, 5.50%, 5.55%, 5.60%, 5.65%, 5.70%, 5.75%, 5.80%, 5.85%, 5.90%, 5.95%, 6.00%, 6.05%, 6.10%, 6.15%, 6.20%, 6.25%, 6.30%, 6.35%, 6.40%, 6.45%, 6.50%, 6.55%, 6.60%, 6.65%, 6.70%, 6.75%, 6.80%, 6.85%, 6.90%, 6.95%, 7.00%, 7.05%, 7.10%, 7.15%, 7.20%, 7.25%, 7.30%, 7.35%, 7.40%, </xnotran> 7.45%, 7.50%, 7.55%, 7.60%, 7.65%, 7.70%, 7.75%, 7.80%, 7.85%, 7.90%, 7.95%, 8.00%, 8.05%, 8.10%, 8.15%, 8.20%, 8.25%, 8.30%, 8.35%, 8.40%, 8.45%, 8.50%, 8.55%, 8.60%, 8.65%, 8.70%, 8.75%, 8.80%, 8.85%, 8.90%, 8.95%, 9.00%, 9.05%, 9.10%, 9.15%, 9.20%, 9.25%, 9.30%, 9.35%, 9.40%, 9.45%, 9.50%, 9.55%, 9.60%, 9.65%, 9.70%, 9.75%, 9.80%, 9.85%, 9.90%, 9.95%, 10.0%, or any value or range defined by any two thereof, and any subrange or range therebetween.
In one embodiment, the nutritional composition is added in an amount such that the osteopontin content is at least 0.001%, preferably at least 0.002%, preferably at least 0.003%, preferably at least 0.004% and at most 1.0%, preferably at most 0.8%, preferably at most 0.5%, preferably at most 0.4% by weight relative to the total weight of the food product. <xnotran> , , 0.001%, 0.002%, 0.003%, 0.004%, 0.005%, 0.006%, 0.007%, 0.008%, 0.009%, 0.010%, 0.015%, 0.020%, 0.025%, 0.030%, 0.035%, 0.040%, 0.045%, 0.050%, 0.055%, 0.060%, 0.065%, 0.070%, 0.075%, 0.080%, 0.085%, 0.090%, 0.095%, 0.100%, 0.105%, 0.110%, 0.115%, 0.120%, 0.125%, 0.130%, 0.135%, 0.140%, 0.145%, 0.150%, 0.155%, 0.160%, 0.165%, 0.170%, 0.175%, 0.180%, 0.185%, 0.190%, 0.195%, 0.200%, 0.205%, 0.210%, 0.215%, 0.220%, 0.225%, 0.230%, 0.235%, 0.240%, 0.245%, 0.250%, 0.255%, 0.260%, 0.265%, 0.270%, 0.275%, 0.280%, 0.285%, 0.290%, 0.295%, 0.300%, 0.305%, 0.310%, 0.315%, 0.320%, 0.325%, 0.330%, 0.335%, 0.340%, 0.345%, 0.350%, 0.355%, 0.360%, 0.365%, 0.370%, 0.375%, 0.380%, 0.385%, 0.390%, 0.395%, 0.400%, 0.405%, 0.410%, 0.415%, 0.420%, 0.425%, 0.430%, 0.435%, 0.440%, 0.445%, 0.450%, 0.455%, 0.460%, 0.465%, 0.470%, 0.475%, 0.480%, 0.485%, 0.490%, 0.495%, 0.500%, 0.505%, 0.510%, 0.515%, 0.520%, 0.525%, 0.530%, 0.535%, 0.540%, 0.545%, 0.550%, 0.555%, 0.560%, 0.565%, 0.570%, 0.575%, 0.580%, 0.585%, 0.590%, 0.595%, 0.600%, 0.605%, 0.610%, 0.615%, 0.620%, 0.625%, 0.630%, 0.635%, 0.640%, 0.645%, 0.650%, 0.655%, 0.660%, 0.665%, 0.670%, 0.675%, 0.680%, 0.685%, 0.690%, 0.695%, 0.700%, 0.705%, 0.710%, 0.715%, 0.720%, 0.725%, 0.730%, 0.735%, 0.740%, 0.745%, 0.750%, 0.755%, 0.760%, 0.765%, 0.770%, </xnotran> 0.775%, 0.780%, 0.785%, 0.790%, 0.795%, 0.800%, 0.805%, 0.810%, 0.815%, 0.820%, 0.825%, 0.830%, 0.835%, 0.840%, 0.845%, 0.850%, 0.855%, 0.860%, 0.865%, 0.870%, 0.875%, 0.880%, 0.885%, 0.890%, 0.895%, 0.900%, 0.905%, 0.910%, 0.915%, 0.920%, 0.925%, 0.930%, 0.935%, 0.940%, 0.945%, 0.950%, 0.955%, 0.960%, 0.965%, 0.970%, 0.975%, 0.980%, 0.985%, 0.990%, 0.995%, 1.0%, or any two thereof, as well as ranges bounded by any values and subranges within the ranges and any values and subranges subsumed therein.
In one embodiment, the nutritional composition is added in an amount such that the weight content of docosahexaenoic acid is at least 0.005%, preferably at least 0.01%, preferably at least 0.02% and at most 5.0%, preferably at most 4.0%, preferably at most 2.0%, relative to the total weight of the food product. <xnotran> , , 0.005%, 0.006%, 0.007%, 0.008%, 0.009%, 0.010%, 0.015%, 0.020%, 0.025%, 0.030%, 0.035%, 0.040%, 0.045%, 0.050%, 0.055%, 0.060%, 0.065%, 0.070%, 0.075%, 0.080%, 0.085%, 0.090%, 0.095%, 0.100%, 0.105%, 0.110%, 0.115%, 0.120%, 0.125%, 0.130%, 0.135%, 0.140%, 0.145%, 0.150%, 0.155%, 0.160%, 0.165%, 0.170%, 0.175%, 0.180%, 0.185%, 0.190%, 0.195%, 0.200%, 0.205%, 0.210%, 0.215%, 0.220%, 0.225%, 0.230%, 0.235%, 0.240%, 0.245%, 0.250%, 0.255%, 0.260%, 0.265%, 0.270%, 0.275%, 0.280%, 0.285%, 0.290%, 0.295%, 0.300%, 0.305%, 0.310%, 0.315%, 0.320%, 0.325%, 0.330%, 0.335%, 0.340%, 0.345%, 0.350%, 0.355%, 0.360%, 0.365%, 0.370%, 0.375%, 0.380%, 0.385%, 0.390%, 0.395%, 0.400%, 0.405%, 0.410%, 0.415%, 0.420%, 0.425%, 0.430%, 0.435%, 0.440%, 0.445%, 0.450%, 0.455%, 0.460%, 0.465%, 0.470%, 0.475%, 0.480%, 0.485%, 0.490%, 0.495%, 0.500%, 0.505%, 0.510%, 0.515%, 0.520%, 0.525%, 0.530%, 0.535%, 0.540%, 0.545%, 0.550%, 0.555%, 0.560%, 0.565%, 0.570%, 0.575%, 0.580%, 0.585%, 0.590%, 0.595%, 0.600%, 0.605%, 0.610%, 0.615%, 0.620%, 0.625%, 0.630%, 0.635%, 0.640%, 0.645%, 0.650%, 0.655%, 0.660%, 0.665%, 0.670%, 0.675%, 0.680%, 0.685%, 0.690%, 0.695%, 0.700%, 0.705%, 0.710%, 0.715%, 0.720%, 0.725%, 0.730%, 0.735%, 0.740%, 0.745%, 0.750%, 0.755%, 0.760%, 0.765%, 0.770%, 0.775%, 0.780%, 0.785%, 0.790%, </xnotran> 0.795%, 0.800%, 0.805%, 0.810%, 0.815%, 0.820%, 0.825%, 0.830%, 0.835%, 0.840%, 0.845%, 0.850%, 0.855%, 0.860%, 0.865%, 0.870%, 0.875%, 0.880%, 0.885%, 0.890%, 0.895%, 0.900%, 0.905%, 0.910%, 0.915%, 0.920%, 0.925%, 0.930%, 0.935%, 0.940%, 0.945%, 0.950%, 0.955%, 0.960%, 0.965%, 0.970%, 0.975%, 0.980%, 0.985%, 0.990%, 0.995%, 1.00%, 1.05%, 1.10%, 1.15%, 1.20%, 1.25%, 1.30%, 1.35%, 1.40%, 1.45%, 1.50%, 1.55%, 1.70%, 1.90%, 1.75%, 1.80%, 1.0.80%, 1.75%, 1.85%, 1.0.05%, 1.80%, 1.0.80%, 1.75%, 1.0.80%, 1.05%, 1.10%, 1.15%, 1.80%, 1.0.95%, 1.0.80%, 1.75%, 1.0%, 1.75%, 1. 2.20%, 2.25%, 2.30%, 2.35%, 2.40%, 2.45%, 2.50%, 2.55%, 2.60%, 2.65%, 2.70%, 2.75%, 2.80%, 2.85%, 2.90%, 2.95%, 3.00%, 3.05%, 3.10%, 3.15%, 3.20%, 3.25%, 3.30%, 3.35%, 3.40%, 3.45%, 3.50%, 3.55%, 3.60%, 3.65%, 3.70%, 3.75%, 3.80%, 3.85%, 3.90%, 3.95%, 4.00%, 4.05%, 4.10%, 4.15%, 4.20%, 4.25%, 4.30%, 4.35%, 4.40%, 4.45%, 4.50%, 4.55%, 4.60%, 4.65%, 4.70%, 4.75%, 4.80%, 4.85%, 4.90%, 4.95%, 5.00%, or any range or both of these values and any range subsumed therein.
In one embodiment, the nutritional composition is added in an amount such that the weight content of 2 '-fucosyllactose (2' -FL) is 0.04-4%, the weight content of docosahexaenoic acid is 0.02-2.0%, and the weight content of osteopontin is 0.004-0.4%, relative to the total weight of the food product.
When the contents of 2' -fucosyllactose, docosahexaenoic acid, and osteopontin in the food are in the above ranges, neural development promoting neuronal maturation, synaptogenesis, and/or myelination can be significantly promoted while balancing various nutrients, and in particular, the myelination property of OPC, which is proliferated, matured, and/or differentiated into mature OLs and/or OL, can be promoted.
As mentioned above, the nutritional composition may optionally further comprise:
-a carbohydrate selected from yeast beta-glucan and/or polydextrose; and/or
-a peptide or amino acid selected from casein phosphopeptide (CPP) and/or L-cystine and/or L-phenylalanine; and/or
-vitamins selected from pantothenic acid and/or biotin; and/or
-minerals selected from sodium citrate and/or potassium chloride.
In one embodiment, when yeast beta-glucan is present in the nutritional composition, the nutritional composition is added in an amount such that the weight content of yeast beta-glucan in the food product may be 0.001-2.5% relative to the total weight of the food product, e.g., 0.001%, 0.002%, 0.003%, 0.004%, 0.005%, 0.006%, 0.007%, 0.008%, 0.009%, 0.01%, 0.02%, 0.03%, 0.04%, 0.05%, 0.06%, 0.07%, 0.08%, 0.09%, 0.10%, 0.15%, 0.20%, 0.25%, 0.30%, 0.35%, 0.40%, 0.45%, 0.50%, 0.55%, 0.60%, 0.65%, 0.70%, 0.75%, 0.80%, 0.85%, 0.90%, 0.95%, 1.00%, 1.05% 1.10%, 1.15%, 1.20%, 1.25%, 1.30%, 1.35%, 1.40%, 1.45%, 1.50%, 1.55%, 1.60%, 1.65%, 1.70%, 1.75%, 1.80%, 1.85%, 1.90%, 1.95%, 2.00%, 2.05%, 2.10%, 2.15%, 2.20%, 2.25%, 2.30%, 2.35%, 2.40%, 2.45%, 2.50%, or a range defined by any two thereof and including any values and subranges within the range.
<xnotran> , , , , 0.02-40%, 0.02%, 0.03%, 0.04%, 0.05%, 0.06%, 0.07%, 0.08%, 0.09%, 0.10%, 0.15%, 0.20%, 0.25%, 0.30%, 0.35%, 0.40%, 0.45%, 0.50%, 0.55%, 0.60%, 0.65%, 0.70%, 0.75%, 0.80%, 0.85%, 0.90%, 0.95%, 1.00%, 1.10%, 1.20%, 1.30%, 1.40%, 1.50%, 1.60%, 1.70%, 1.80%, 1.90%, 2.00%, 2.10%, 2.20%, 2.30%, 2.40%, 2.50%, 2.60%, 2.70%, 2.80%, 2.90%, 3.00%, 3.10%, 3.20%, 3.30%, 3.40%, 3.50%, 3.60%, 3.70%, 3.80%, 3.90%, 4.00%, 4.10%, 4.20%, 4.30%, 4.40%, 4.50%, 4.60%, 4.70%, 4.80%, 4.90%, 5.00%, 5.10%, 5.20%, 5.30%, 5.40%, 5.50%, 5.60%, 5.70%, 5.80%, 5.90%, 6.00%, 6.10%, 6.20%, 6.30%, 6.40%, 6.50%, 6.60%, 6.70%, 6.80%, 6.90%, 7.00%, 7.10%, 7.20%, 7.30%, 7.40%, 7.50%, 7.60%, 7.70%, 7.80%, 7.90%, 8.00%, 8.10%, 8.20%, 8.30%, 8.40%, 8.50%, 8.60%, 8.70%, 8.80%, 8.90%, 9.00%, 9.10%, 9.20%, 9.30%, 9.40%, 9.50%, 9.60%, 9.70%, 9.80%, 9.90%, 10.0%, 10.5%, 11.0%, 11.5%, 12.0%, 12.5%, 13.0%, 13.5%, 14.0%, 14.5%, 15.0%, 15.5%, 16.0%, 16.5%, 17.0%, 17.5%, 18.0%, 18.5%, 19.0%, 19.5%, 20.0%, 20.5%, 21.0%, 21.5%, 22.0%, 22.5%, 23.0%, 23.5%, 24.0%, </xnotran> 24.5%, 25.0%, 25.5%, 26.0%, 26.5%, 27.0%, 27.5%, 28.0%, 28.5%, 29.0%, 29.5%, 30.0%, 30.5%, 31.0%, 31.5%, 32.0%, 32.5%, 33.0%, 33.5%, 34.0%, 34.5%, 35.0%, 35.5%, 36.0%, 36.5%, 37.0%, 37.5%, 38.0%, 38.5%, 39.0%, 39.5%, 40.0%, or a range defined by any two thereof and any values and subranges encompassed within that range.
In one embodiment, when casein phosphopeptides (CPP) are present in the nutritional composition, the nutritional composition is added in an amount such that the casein phosphopeptides (CPP) may be present in the food product in an amount of 0.01-2% by weight relative to the total weight of the food product, for example, 0.01%, 0.02%, 0.03%, 0.04%, 0.05%, 0.06%, 0.07%, 0.08%, 0.09%, 0.10%, 0.15%, 0.20%, 0.25%, 0.30%, 0.35%, 0.40%, 0.45%, 0.50%, 0.55%, 0.60%, 0.65%, 0.70%, 0.75%, 0.80%, 0.85%, 0.90%, 0.95%, 1.00%, 1.05%, 1.10%, 1.15%, 1.20%, 1.25%, 1.30%, 1.35%, 1.40%, 1.45%, 1.50%, 1.55%, 1.60%, 1.65%, 1.70%, 1.75%, 1.80%, 1.85%, 1.90%, 1.95%, 2.00%, or a range defined by any two thereof, as well as any values and subranges encompassed within this range.
In one embodiment, when L-cystine is present in the nutritional composition, the nutritional composition is added in an amount such that the weight content of L-cystine in the food product, relative to the total weight of the food product, can be 0.01-0.8%, e.g., 0.01%, 0.02%, 0.03%, 0.04%, 0.05%, 0.06%, 0.07%, 0.08%, 0.09%, 0.10%, 0.15%, 0.20%, 0.25%, 0.30%, 0.35%, 0.40%, 0.45%, 0.50%, 0.55%, 0.60%, 0.65%, 0.70%, 0.75%, 0.80%, or a range defined by any two thereof and any values and subranges subsumed therein.
In one embodiment, when L-phenylalanine is present in the nutritional composition, the nutritional composition is added in an amount such that the weight content of L-phenylalanine in the food product, relative to the total weight of the food product, can be 0.002-0.8%, for example, 0.002%, 0.003%, 0.004%, 0.005%, 0.006%, 0.007%, 0.008%, 0.009%, 0.01%, 0.02%, 0.03%, 0.04%, 0.05%, 0.06%, 0.07%, 0.08%, 0.09%, 0.10%, 0.15%, 0.20%, 0.25%, 0.30%, 0.35%, 0.40%, 0.45%, 0.50%, 0.55%, 0.60%, 0.65%, 0.70%, 0.75%, 0.80%, or a range defined by any two thereof and any values and subranges subsumed therein.
In one embodiment, when pantothenic acid is present in the nutritional composition, the nutritional composition is added in an amount such that the weight content of pantothenic acid in the food can be 0.001% to 0.1% relative to the total weight of the food, e.g., 0.001%, 0.0015%, 0.002%, 0.0025%, 0.003%, 0.004%, 0.005%, 0.006%, 0.007%, 0.008%, 0.009%, 0.01%, 0.015%, 0.02%, 0.025%, 0.03%, 0.035%, 0.04%, 0.045%, 0.05%, 0.055%, 0.06%, 0.065%, 0.07%, 0.075%, 0.08%, 0.085%, 0.09%, 0.095%, 0.10%, or a range defined by any two thereof and any values and subranges subsumed therein.
In one embodiment, when biotin is present in the nutritional composition, the nutritional composition is added in an amount such that the weight content of biotin in the food product can be 0.000001% to 0.0001%, e.g., 0.000001%, 0.000002%, 0.000003%, 0.000004%, 0.000005%, 0.000006%, 0.000007%, 0.000008%, 0.000009%, 0.00001%, 0.000015%, 0.00002%, 0.000025%, 0.00003%, 0.000035%, 0.00004%, 0.000045%, 0.00005%, 0.000055%, 0.00006%, 0.000065%, 0.00007%, 0.000075%, 0.00008%, 0.000085%, 0.00009%, 0.000095%, 0.0001%, or a range defined by any two thereof and any values and subranges subsumed therein, relative to the total weight of the food product.
<xnotran> , , , , 0.02-8%, 0.02%, 0.03%, 0.04%, 0.05%, 0.06%, 0.07%, 0.08%, 0.09%, 0.10%, 0.15%, 0.20%, 0.25%, 0.30%, 0.35%, 0.40%, 0.45%, 0.50%, 0.55%, 0.60%, 0.65%, 0.70%, 0.75%, 0.80%, 0.85%, 0.90%, 0.95%, 1.00%, 1.10%, 1.20%, 1.30%, 1.40%, 1.50%, 1.60%, 1.70%, 1.80%, 1.90%, 2.00%, 2.10%, 2.20%, 2.30%, 2.40%, 2.50%, 2.60%, 2.70%, 2.80%, 2.90%, 3.00%, 3.10%, 3.20%, 3.30%, 3.40%, 3.50%, 3.60%, 3.70%, 3.80%, 3.90%, 4.00%, 4.10%, 4.20%, 4.30%, 4.40%, 4.50%, 4.60%, 4.70%, 4.80%, 4.90%, 5.00%, 5.10%, 5.20%, 5.30%, 5.40%, 5.50%, 5.60%, 5.70%, 5.80%, 5.90%, 6.00%, 6.10%, 6.20%, 6.30%, 6.40%, 6.50%, 6.60%, 6.70%, 6.80%, 6.90%, 7.00%, 7.10%, 7.20%, 7.30%, 7.40%, 7.50%, 7.60%, 7.70%, 7.80%, 7.90%, 8.00%, . </xnotran>
<xnotran> , , , , 0.02-8%, 0.02%, 0.03%, 0.04%, 0.05%, 0.06%, 0.07%, 0.08%, 0.09%, 0.10%, 0.15%, 0.20%, 0.25%, 0.30%, 0.35%, 0.40%, 0.45%, 0.50%, 0.55%, 0.60%, 0.65%, 0.70%, 0.75%, 0.80%, 0.85%, 0.90%, 0.95%, 1.00%, 1.10%, 1.20%, 1.30%, 1.40%, 1.50%, 1.60%, 1.70%, 1.80%, 1.90%, 2.00%, 2.10%, 2.20%, 2.30%, 2.40%, 2.50%, 2.60%, 2.70%, 2.80%, 2.90%, 3.00%, 3.10%, 3.20%, 3.30%, 3.40%, 3.50%, 3.60%, 3.70%, 3.80%, 3.90%, 4.00%, 4.10%, 4.20%, 4.30%, 4.40%, 4.50%, 4.60%, 4.70%, 4.80%, 4.90%, 5.00%, 5.10%, 5.20%, 5.30%, 5.40%, 5.50%, 5.60%, 5.70%, 5.80%, 5.90%, 6.00%, 6.10%, 6.20%, 6.30%, 6.40%, 6.50%, 6.60%, 6.70%, 6.80%, 6.90%, 7.00%, 7.10%, 7.20%, 7.30%, 7.40%, 7.50%, 7.60%, 7.70%, 7.80%, 7.90%, 8.00%, . </xnotran>
When the food further comprises the optional substances in the content range, the food can more remarkably promote the neural development such as neuron maturation, synaptogenesis and/or myelination, particularly promote the proliferation, maturation and/or differentiation of OPC into mature OLs and/or OL myelination characteristics, and simultaneously more balance various nutrients required by the body.
In addition to the components described above for the nutritional composition, the food product may comprise other ingredients, such as other proteins, carbohydrates, fats, vitamins, minerals, etc. that are often contained in formulas, such as infant formulas like milk powder.
Use of
In a further aspect the present invention relates to the use of the above nutritional composition or the above food product for non-therapeutic purposes (nutritional and health) in improving brain development and intelligence, especially in promoting neurological development (e.g. promoting the proliferation, maturation and/or differentiation of OPC into mature OLs and/or OLs) in infants and young children.
Examples
In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is further described in detail with reference to the following embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention. The reagents, methods and apparatus employed in the present invention are those conventional in the art, unless otherwise specified.
Raw materials
In the examples section that follows, the starting materials used are as follows, unless otherwise indicated.
2 '-fucosyllactose (2' -FL): glyCare TM 2FL 9000,2' -fucosyllactose content 96.0% by mass
Osteopontin: the osteopontin powder Lacprodan OPN-10 of the groups P/S of Arla Foods, denmark, with an osteopontin content of 95.6% by mass
Docosahexaenoic acid: docosahexaenoic acid oil of Jiabiyou Biotech (Wuhan) Co., ltd., DHA content 7% by mass
In the following section, unless otherwise specified, when referring to parts by mass and ratios of ingredients in the nutritional composition, the parts by mass refer to parts by mass of 2 '-fucosyllactose (2' -FL), docosahexaenoic acid and osteopontin as active ingredients, and the ratios refer to mass ratios between 2 '-fucosyllactose (2' -FL), docosahexaenoic acid and osteopontin as active ingredients.
Various nutritional compositions were formulated by mixing 2 '-fucosyllactose (2' -FL) raw material, docosahexaenoic acid (DHA) raw material, and Osteopontin (OPN) raw material in the proportions shown in the following examples, the compositions of which are shown in table 1.
TABLE 1 composition of nutritional compositions
Examples of cell experiments
At present, the research on the brain development is limited to the research on the passive memory by using animal experiments, the development of neuronal cells is not discussed, and the influence of the specific dosage of the composition on the early development of the brain is not explored. The present invention uses an in vitro model of primary cell culture containing neurons and OPCs to assess the effect of the nutritional cocktail on myelination and neurons. Through experimental study on the influence of components containing 2' -FL, DHA and OPN in different proportions on the development of brain nerve cells, the method systematically and intuitively evaluates the influence on early brain development, and has profound significance for guiding the application of the composition.
1 materials and methods
1.1 Instrument and reagent consumables
A cell incubator; laser confocal fluorescence microscopy; a centrifuge; an electronic balance; vortex instrument, water bath, tissue homogenizer.
A neural cell culture medium; antibodies such as A2B5, MAG, MBP, etc.
1.2 Experimental methods
1.2.1 neural Primary cell acquisition
All experiments were ethically approved and primary mixed neuronal and OLs cultures were performed as follows. Briefly, the forebrains of newborn mice were dissociated with Trypsin (Trypsin EDTA 1X, PAN BIOTECH) at 37 ℃ for 20 minutes. After adding Dulbecco's modified Eagle's medium (DMEM, PAN BIOTECH) containing DNAse class I II (0.1 mg/ml, PAN BIOTECH) and 10% fetal calf serum (FCS, GIBCO), the reaction was stopped. Cells were mechanically separated three times by a 10ml pipette and then centrifuged at 515g for 10 min at 4 ℃.
Viable cells were seeded in 96-well plates (20000/well) pre-coated with poly-L-lysine (BD Falcon) and laminin (Sigma). The medium consisted of Neurobasal (GIBCO) supplemented with 2% B27 (GIBCO), 2mM L-glutamine (LGlu, PAN BIOTECH), 2% P/S solution (PAN BIOTECH), 1% FCS and 10ng/ml platelet-derived growth factor (PDGF-AA, PAN BIOTECH). The 96-well plates were stored in humidified incubators at 37 ℃ with ambient air (95%) -CO2 (5%).
1.2.2 neural cell culture
The same number of cells were placed in 48-well plates and then incubated between 12, 18 or 30DIV, half of the medium was changed every other day, and either the mixture or individual nutrients (nutritional composition containing 2' -FL, DHA and/or OPN prepared above) were added to the fresh medium.
1.2.3 immunohistochemical experiments
12. After 18 and 30DIV, the cells were fixed by exposure to a cold mixture of 95% ethanol and acetic acid (5%) for 5 minutes. Non-specific sites were then blocked with Phosphate Buffered Saline (PBS) solution containing 0.1% saponin (Sigma) and 1% FCS (GIBCO) for 15 min at room temperature.
At 12DIV, neural cells were incubated with mouse monoclonal antibody A2B5 (dilution: 1/200, millipore, MAB312RX) for 2h at room temperature, followed by incubation with neurofilamin antibody (dilution: 1/500, sigma, N4142) for 2h at room temperature. Finally, a secondary goat anti-rabbit antibody (dilution 1/400, SIGMA, SAB4600084) was used for co-incubation at room temperature for 1h.
At 18DIV, the neural cells were incubated for 2h with the mouse monoclonal antibody MAG (dilution: 1/400, millipore, MAB1567) and the neurofilament antibody (dilution: 1/500, sigma, N4142). The cells were then incubated with secondary goat anti-rabbit antibodies (dilution: 1/400, sigma, SAB4600042) and secondary goat anti-rabbit antibodies (dilution: 1/400, SIGMA, SAB4600084) for 1h at room temperature.
At 30DIV, neural cells were incubated with mouse monoclonal antibody MBP (dilution: 1/1000, novus, NBP1-05204) and neurofilamin antibody (dilution: 1/500, sigma, N4142) for 2h. Then, the cells were incubated with a secondary goat anti-mouse antibody (dilution: 1/800, sigma, SAB4600042) and a secondary goat anti-rabbit antibody (dilution: 1/400, SIGMA, SAB4600084) for 1h at room temperature.
1.2.4 microscopic photograph
ImageXpress was used for 20 magnification and equipped with LED lamps (excitation 360/480/565 and emission 460/535/620). All images were acquired using the same settings.
The number of OPCs was calculated by quantification of the number of A2B5 expressing cells under 12DIV conditions and the results were expressed as the average number of A2B5 expressing cells per well per panel.
Differentiation of OPCs into OLs was assessed by counting the number of MAG positive cells in cell culture at 18 DIV. Results are expressed in mean cell number per picture and per well. The morphological maturation of MAG-positive cells was assessed by measuring the average surface area of MAG-positive cells in 18DIV wells (. Mu.m/map/well).
The maturation of the OLs was estimated by counting the number of MBP positive cells (average number of cells per picture per well) and the average surface area of MBP positive cells at 30DIV (μm per picture per well) at 30 DIV.
1.3 cell assay grouping
Cells were seeded in 96-well plates and cultured for a period of time, half of the medium was replaced every other day, and fresh primary cell-specific medium was supplemented with different concentrations of either mixed or individual 2FL mixtures (12, 18, 30d added separately), 6 replicates per sample. The blank control group, positive control group and sample run group were compared with each other using Olesoxime (300 nM, demonstrated to accelerate OLs maturation and myelination in vitro and in vivo) as a positive control. Immunohistochemistry (MBP, NF, A2B 5) measures the effect of OPN and 2FL, DHA, alone or in combination, on the population of OPCs, OL maturation and differentiation, myelin formation and neurite outgrowth. The specific experimental doses are given in table 2 below.
TABLE 2 Experimental dosages of cells
1.4 statistical analysis
Results are expressed as mean ± standard error, and significant differences were judged when p <0.05 using SPSS software for both T-test and one-way ANOVA (T-test and one-way ANOVA) tests.
2 results of the experiment
2.1 Effect of Each sample on nerve cells
To evaluate the effect of mixed nutrition or nutrient treatment alone on OPCs, we assessed the number of labeled A2B5 positive cells after 12DIV to estimate the number of OPCs.
FIG. 1 shows the effect of samples of different nutritional compositions on neural cells after 12d in vitro culture-A2B 5 immunostaining (green). Scale bar 50 μm. The average A2B5 positive cell number per picture and per well measured is shown in table 3.
TABLE 3 Effect of different nutritional composition samples comprising 2' -FL, OPN and/or DHA on the number of A2B5 positive cells
2.2 Effect of samples on OPC cell myelination
To measure the effect of mixed or single nutrient treatments on OPCs cell myelination, we assessed the number of positive cells labeled MAG after 18 DIV.
FIG. 2 shows the effect of samples of different nutritional compositions on neural cells after 18d in vitro culture-MAG immunostaining (green). Scale bar 50 μm. The average MAG-positive cell number per picture and per well measured is shown in Table 4.
TABLE 4 Effect of different nutritional composition samples containing 2' -FL, OPN and/or DHA on MAG-positive cell number
2.3 Effect of samples on OPC cell maturation
To measure the effect of mixed or single nutrient treatments on cell maturation of OPCs, we assessed the number of positive cells labeled MBP after 30 DIV.
FIG. 3 shows the effect of different nutrient composition samples on nerve cells after 30d in vitro culture-MBP immunostaining (green). Scale bar 50 μm. The average number of MBP-positive cells per picture and per well measured is shown in table 5.
TABLE 5 Effect of different nutritional composition samples comprising 2' -FL, OPN and/or DHA on the number of MBP-positive cells
2.4 discussion of results
(2.4.1) combination of 2' -FL and OPN
As can be seen from tables 3 to 5, the cell experiment examples 24 to 28 (corresponding to examples 1 to 3) using 2' -FL in combination with OPN significantly increased the number of A2B 5-positive cells, MAG-positive cells, and/or MBP-positive cells compared to the blank control group (cell experiment example 1), and the combination thereof could achieve better effects than the individual components thereof, indicating that the combination thereof contributes to the proliferation of oligodendrocyte precursor cells, myelination of oligodendrocyte precursor cells, and/or maturation of oligodendrocyte precursor cells.
In addition, as can be seen from tables 3-5, when 2' -FL and OPN were used in combination, there was a synergistic effect between the two, which synergistically increased the number of A2B 5-positive cells, the number of MAG-positive cells and/or the number of MBP-positive cells.
For example, with respect to the components used and the amounts thereof,
cell experiment example 24 corresponds to a combination of cell experiment examples 4 and 8. Compared with the blank control group (namely the cell experiment example 1), the number of the MBP positive cells is increased by 21.5, 12.207 and 3.047 respectively, wherein the former (21.5) is larger than the sum (15.254) of the latter two, which shows that the MBP positive cells can be increased synergistically.
Cell experiment example 25 corresponds to the combination of cell experiment examples 5 and 9. Compared with the blank control group (namely the cell experiment example 1), the number of the MBP positive cells is increased by 53.334, 30.927 and 7.317 respectively, the former (53.334) is larger than the sum (38.244) of the latter two, which shows that the MBP positive cells can be increased synergistically.
Cell experiment example 26 corresponds to the combination of cell experiment examples 7 and 8, and with respect to the blank control group (i.e., cell experiment example 1),
it increases the number of A2B5 positive cells by 35.5, 23.334, 4.117, respectively, the former (35.5) being greater than the sum of the latter (27.451), indicating that both are able to synergistically increase the number of A2B5 positive cells;
it increases the number of A2B5 positive cells by 26.667, 21.834, 1.207, respectively, the former (26.667) being greater than the sum of the latter (23.041), indicating that both are able to synergistically increase the number of MAG positive cells;
it increases the number of MBP positive cells by 45.167, 34.667, 3.047, respectively, the former (45.167) being greater than the sum of the latter (37.714), indicating that both are able to increase the number of MBP positive cells synergistically.
Cellular experiment example 27 corresponds to the combination of cellular experiment examples 7 and 11, and with respect to the blank control group (i.e., cellular experiment example 1),
it increases the number of A2B5 positive cells by 47.834, 23.334, 19.834, respectively, the former (47.834) being greater than the sum of the latter (43.168), indicating that both are able to synergistically increase the number of A2B5 positive cells;
it increases the number of MBP positive cells by 84.167, 34.667, 28.834, respectively, the former (84.167) being greater than the sum of the latter (63.501), indicating that both are able to synergistically increase the number of MBP positive cells.
Cellular experiment example 28 corresponds to a combination of cellular experiment examples 6 and 10. Compared with a blank control group (namely cell experiment example 1), the number of the MBP positive cells is increased by 78.5, 25.227 and 17.697 respectively, and the former (78.5) is larger than the sum (42.924) of the two, which shows that the MBP positive cells can be synergistically increased by the two.
Thus, the results of tables 3-5 indicate that when 2' -FL and OPN are used in combination (e.g. at a mass ratio of 10.
(2.4.2) combination of 2' -FL, OPN and DHA
As can also be seen from tables 3-5, when DHA was further added to the combination of 2'-FL and OPN, cell experiment examples 16-23 (corresponding to examples 4-7) could further significantly increase the number of A2B5 positive cells, MAG positive cells, and/or MBP positive cells, and could achieve better effects than the individual components therein and/or better effects than the combination of 2' -FL and OPN, indicating that their combination contributed to the proliferation of oligodendrocyte precursor cells, myelination of oligodendrocyte precursor cells, and/or maturation of oligodendrocyte precursor cells.
In addition, as can be seen from tables 3-5, when 2' -FL, OPN and DHA are used in combination, there may be a synergistic effect between the three, for example, the number of A2B5 positive cells, the number of MAG positive cells and/or the number of MBP positive cells may be synergistically increased.
For example, the cell experiment example 16 corresponds to the combination of the cell experiment examples 4, 8 and 12 in terms of the components used and the amounts thereof, which respectively increase the number of MBP-positive cells by 28.334, 12.204, 3.047 and 6.307, the former (28.334) being greater than the sum (21.561) of the latter, compared to the blank control group (i.e., cell experiment example 1), indicating that the three can synergistically increase the number of MBP-positive cells. In addition, the cellular experiment example 16 also corresponds to the combination of the cellular experiment examples 24 and 12, and the number of MBP-positive cells was increased by 28.334, 21.5, and 6.307, respectively, with the former (28.334) being greater than the sum (27.807) of the latter, compared with the blank control group (i.e., the cellular experiment example 1).
Cell experiment example 17 corresponds to the combination of cell experiment examples 5, 9 and 13, which respectively increased the number of MBP-positive cells by 57.687, 30.927, 7.317 and 15.867, the former (57.687) being greater than the sum of the latter (54.111), indicating that the three synergistically increased the number of MBP-positive cells, relative to the blank control group (i.e., cell experiment example 1).
Cellular experiment example 20 corresponds to the combination of cellular experiment examples 6, 10, and 14, and it was found that the number of MBP-positive cells was increased by 90.667, 25.227, 17.697, and 33.157, respectively, in comparison with the blank control group (i.e., cellular experiment example 1), and the former (90.667) was greater than the sum (76.081) of the latter, indicating that the three groups synergistically increased the number of MBP-positive cells.
Cellular experiment example 23 corresponds to the combination of cellular experiment examples 3, 8 and 15, and with respect to the blank control group (i.e., cellular experiment example 1),
it increases the number of A2B5 positive cells by 34.277, 2.897, 4.117, 25.5, respectively, the former (34.277) being greater than the sum of the latter (32.514), indicating that the three are able to synergistically increase the number of A2B5 positive cells;
it increased the number of MAG positive cells by 25.317, 0.607, 1.207, 18.167, respectively, the former (25.317) being greater than the sum of the latter (19.981), indicating that the three were able to synergistically increase the number of MAG positive cells.
Thus, the results of tables 3-5 indicate that when 2' -FL, OPN and DHA are used in combination, the number of A2B5 positive cells, MAG positive cells and/or MBP positive cells may be further significantly increased, and there may be synergy between the three, indicating that the combination may significantly promote, for example, the myelinating properties of OPCs to synergistically promote their proliferation, maturation and/or differentiation into mature OLs and/or OLs.
The invention provides a research on the brain development, especially the neural development of Osteopontin (OPN), 2 '-fucosyllactose (2' -FL) and docosahexaenoic acid (DHA) compositions, and provides a new idea for the development of future functional foods. Osteopontin, 2 '-fucosyllactose (2' -FL) and docosahexaenoic acid (DHA) have wide prospects in improving memory and brain development, and researches show that an extracellular environment plays an important role in regulating brain homeostasis, controlling myelination and other cell mechanisms in the development process of a central nervous system. Deficiency of key nutrients can significantly affect brain development. Our studies show that brain cell cultures treated with a combination of 2' -FL, OPN, DHA increase the number of OPCs, differentiate or mature into the myelin properties of OLs and OLs in an in vitro model, with a better synergistic effect between the components.
Application examples
In the following application examples, the "parts" are parts by weight, and the% contents of the components are% by weight.
In addition, in each application example below, the following raw material sources were used as follows unless otherwise specified.
Whole milk powder: heilongjiang Feihe Dairy Co Ltd
Enriched osteopontin concentrated whey protein powder (osteopontin 5.2%): ara Foods Ingredients Group P/S, denmark
2 '-fucosyllactose (96.0% 2' -fucosyllactose): glyCare TM 2FL 9000
Docosahexenoic acid fat (DHA 7%): jiabiyou biotechnology (Wuhan) Limited
Desalting whey powder: french Euroserum (Red bird)
Galacto-oligosaccharide: bowling Bao biological shares Ltd
Mixing vegetable oil: jiaji grain oil (Nantong) Co., ltd
Compounding vitamins: dismanan vitamin (Shanghai) Co Ltd
Compounding minerals: dismaman vitamin (Shanghai) Co Ltd
Whole milk powder: heilongjiang Feihe Dairy Co Ltd
Osteopontin powder (osteopontin 95.6%): ara Foods Ingredients Group P/S, lacprodan OPN-10, denmark
Solid corn syrup bowling-Bao biological shares Ltd
Fructo-oligosaccharide: bowling Bao biological shares Ltd
And (3) skim milk powder: ireland Kerry
Isomaltooligosaccharide: bowling Bao biological shares Ltd
Raw milk: heilongjiang Feihe Dairy Co Ltd
Mono-diglycerol fatty acid ester: danisco (China) Ltd
Application example 1
Infant formula containing 2' -fucosyllactose and osteopontin, docosacene hexa-acid (DHA), prepared from the following components in parts by weight per 1000 parts of infant formula:
the milk powder of the invention uses the following raw materials: 195 parts of whole milk powder, 3.85 parts of osteopontin-rich concentrated whey protein powder (5.2 percent of osteopontin in each part), 2.08 parts of 2' -fucosyllactose (96.0 percent of 2' -fucosyllactose in each part), 14 parts of docosahexenoic acid grease (DHA, 14 parts of DHA 7 percent in each part), 350 parts of desalted whey powder, 117 parts of lactose, 123.07 parts of galacto-oligosaccharide, 180 parts of mixed vegetable oil, 2 parts of sodium citrate, 2 parts of potassium chloride, 6 parts of calcium citrate, 3 parts of compound vitamin and 2 parts of compound mineral, wherein the raw materials are uniformly mixed, pasteurized, homogenized, evaporated, concentrated and spray-dried to obtain a powdery semi-finished product, and the uniformly mixed milk powder is filled with nitrogen to be packaged to obtain the final product, wherein the content of the 2' -fucosyllactose in the product is 0.2 percent, the osteopontin is 0.02 percent, and the docosahexenoic acid is 0.1 percent.
Application example 2
Infant formula containing 2' -fucosyllactose and osteopontin, prepared from the following components in parts by weight per 1000 parts of infant formula:
the milk powder of the invention uses the following raw materials: 183 parts of whole milk powder, 7.7 parts of osteopontin-rich concentrated whey protein powder (5.2% of osteopontin in each part), 4.2 parts of 2 '-fucosyllactose (96.0% of 2' -fucosyllactose in each part), 28.57 parts of docosacene hexaacid grease (DHA) (7% of DHA in each part), 350 parts of desalted whey powder, 175 parts of lactose, 52.07 parts of galacto-oligosaccharide, 180 parts of mixed vegetable oil, 2 parts of sodium citrate, 2 parts of potassium chloride, 6 parts of calcium citrate, 3 parts of compound vitamin and 2 parts of compound mineral; mixing the above materials, pasteurizing, homogenizing, evaporating for concentration, spray drying to obtain semi-finished powder, and packaging the mixed milk powder with nitrogen to obtain the final product. The product contains 0.4% of 2' -fucosyllactose, 0.04% of osteopontin and 0.2% of docosacene hexaacid.
Application example 3
The infant formula milk powder containing 2' -fucosyllactose and osteopontin is prepared from the following components in parts by weight per 1000 parts of infant formula milk powder:
the milk powder of the invention uses the following raw materials: 433 parts of whole milk powder, 3.85 parts of osteopontin-rich concentrated whey protein powder (5.2 parts of osteopontin in each part), 2.08 parts of 2 '-fucosyllactose (96.0 parts of 2' -fucosyllactose in each part), 14.29 parts of docosacene hexaacid grease (DHA) (7 parts of DHA in each part), 350 parts of desalted whey powder, 48 parts of lactose, 64.78 parts of galacto-oligosaccharide, 75 parts of mixed vegetable oil, 5 parts of calcium citrate, 3 parts of compound vitamin and 1 part of compound mineral; mixing the above materials, pasteurizing, homogenizing, evaporating for concentration, spray drying to obtain semi-finished powder, and packaging the mixed milk powder with nitrogen to obtain the final product. The product contains 0.2% of 2' -fucosyllactose, 0.02% of osteopontin and 0.1% of docosacene hexaacid.
Application example 4
The modified milk powder containing 2' -fucosyllactose and osteopontin is suitable for pregnant women, and each 1000 parts of the modified milk powder is prepared from the following components in parts by weight:
the milk powder of the invention uses the following raw materials: 336 parts of whole milk powder, 0.78 part of osteopontin powder (5.2 percent of osteopontin in each part), 0.42 part of 2 '-fucosyllactose (96.0 percent of 2' -fucosyllactose in each part), 0.45 part of docosahexenoic acid grease (DHA) (44.8 percent of DHA in each part), 350 parts of skimmed milk powder, 74.35 parts of lactose, 195 parts of solid corn syrup, 40 parts of isomaltooligosaccharide, 2 parts of compound vitamin and 1 part of compound mineral; mixing the above materials, pasteurizing, homogenizing, evaporating for concentration, spray drying to obtain semi-finished powder, and packaging the mixed milk powder with nitrogen to obtain the final product. The content of 2' -fucosyllactose in the product is 0.04%, osteopontin is 0.004%, and docosacene hexaacid is 0.02%.
Application example 5
The modified milk containing 2' -fucosyllactose and osteopontin is prepared from the following components in parts by weight per 1000 parts of modified milk:
the modified milk comprises 900.74 parts of raw milk, 41.67 parts of 2 '-fucosyllactose (96.0% of 2' -fucosyllactose in each part), 4.18 parts of osteopontin powder (95.6% of osteopontin in each part), 44.6 parts of docosahexenoic acid grease (DHA) (44.8% of DHA in each part), 8.3 parts of fructo-oligosaccharide and 0.5 part of mono-diglycerol fatty acid ester; mixing the above materials, homogenizing, UHT sterilizing, homogenizing, and aseptic packaging to obtain the final product. The product contains 4% of 2' -fucosyllactose, 0.4% of osteopontin and 2% of docosacene hexaacid.
Application example 6
The modified milk containing 2' -fucosyllactose and osteopontin is prepared from the following components in parts by weight per 1000 parts of modified milk:
the modified milk comprises 930.29 parts of raw milk, 41.67 parts of 2 '-fucosyllactose (96.0% of 2' -fucosyllactose in each part), 0.78 parts of osteopontin powder (5.2% of osteopontin in each part), 11.2 parts of docosahexenoic acid grease (DHA) (44.8% of DHA in each part), 15.56 parts of fructo-oligosaccharide and 0.5 part of mono-diglycerol fatty acid ester; mixing the above materials, homogenizing, UHT sterilizing, homogenizing, and aseptic packaging to obtain final product. The product contains 1% of 2' -fucosyllactose, 0.1% of osteopontin and 0.5% of docosacene hexaacid.
While the foregoing is directed to embodiments of the present invention, other and further embodiments of the invention may be devised without departing from the basic scope thereof, and the scope thereof is determined by the claims that follow.
Claims (10)
1. A nutritional composition comprising 2' -fucosyllactose, docosahexaenoic acid, and osteopontin.
2. The nutritional composition of claim 1, consisting of 2' -fucosyllactose, docosahexaenoic acid, and osteopontin.
3. The nutritional composition of any one of claims 1-2, wherein:
2' -fucosyllactose is provided in the form of a natural source, and/or a synthetic source, and/or a bacterial fermentation source; and/or
Osteopontin is provided in the form: osteopontin protein powder, and/or osteopontin-containing whey powder.
4. The nutritional composition of any one of claims 1-3, wherein:
the mass ratio of 2' -fucosyllactose to osteopontin in the nutritional composition is from 0.05 to 2000, preferably from 0.1 to 1000, and 1, preferably from 1 to 1000, and
the mass ratio of docosahexaenoic acid to osteopontin in the nutritional composition is 0.02-1000, preferably 0.05-500;
preferably, the mass ratio of 2' -fucosyllactose, docosahexaenoic acid and osteopontin in the nutritional composition is from 0.05 to 2000.
5. The nutritional composition of any one of claims 1-4, further comprising:
-a carbohydrate selected from yeast beta-glucan and/or polydextrose; and/or
-a peptide or amino acid selected from casein phosphopeptide (CPP) and/or L-cystine and/or L-phenylalanine; and/or
-vitamins selected from pantothenic acid and/or biotin; and/or
-minerals selected from sodium citrate and/or potassium chloride;
preferably, when yeast β -glucan is present, its mass ratio to osteopontin is from 0.0025 to 625, preferably from 0.1 to 15;
preferably, when polydextrose is present, the mass ratio thereof to osteopontin is from 0.05 to 10000, preferably from 3.5 to 2000,
preferably, when casein phosphopeptide (CPP) is present, the mass ratio thereof to osteopontin is 0.025 to 500, preferably 0.025 to 55,
preferably, the mass ratio of L-cystine, when present, to osteopontin is from 0.025 to 200, preferably from 0.05 to 25,
preferably, the mass ratio of L-phenylalanine to osteopontin, when present, is from 0.005 to 200, preferably from 0.025 to 20,
preferably, when pantothenic acid is present, its mass ratio to osteopontin is from 0.0025 to 25, preferably from 0.025 to 2.5,
preferably, when biotin is present, its mass ratio to osteopontin is 0.0000025 to 0.025,
preferably, the mass ratio of sodium citrate, when present, to osteopontin is from 0.05 to 2000, preferably from 0.75 to 100,
preferably, when potassium chloride is present, its mass ratio to osteopontin is from 0.05 to 2000, preferably from 0.75 to 100.
6. A food product comprising the nutritional composition of any one of claims 1-5; preferably the food product is in powder or liquid form.
7. The food product of claim 6, which is an infant formula such as an infant formula, a follow-on formula, a toddler formula such as an infant formula, e.g. an infant formula, a toddler formula; supplementary food for infants; a nutritional or dietary supplement; or pregnant woman concocting with milk powder.
8. A food product as claimed in any one of claims 6 to 7, wherein the nutritional composition is added in an amount such that the weight content of 2' -fucosyllactose is at least 0.01%, preferably at least 0.02%, preferably at least 0.03%, preferably at least 0.04% and at most 10.0%, preferably at most 8.0%, preferably at most 5.0%, preferably at most 4.0%, relative to the total weight of the food product, the weight content of osteopontin is at least 0.001%, preferably at least 0.002%, preferably at least 0.003%, preferably at least 0.004% and at most 1.0%, preferably at most 0.8%, preferably at most 0.5%, preferably at most 0.4%, the weight content of docosahexaenoic acid is at least 0.005%, preferably at least 0.01%, preferably at least 0.02% and at most 5.0%, preferably at most 4.0%, preferably at most 2.0%; preferably, the weight content of 2' -fucosyllactose is 0.04-4%, the weight content of docosahexaenoic acid is 0.02-2.0%, and the weight content of osteopontin is 0.004-0.4%.
9. The food product of any one of claims 6-8, wherein:
-when yeast β -glucan is present in the nutritional composition, the nutritional composition is added in an amount such that the weight content of yeast β -glucan in the food product is 0.001-2.5% relative to the total weight of the food product; and/or
-when polydextrose is present in the nutritional composition, the nutritional composition is added in an amount such that the polydextrose content in the food product is comprised between 0.02 and 40% by weight relative to the total weight of the food product; and/or
-when casein phosphopeptide (CPP) is present in the nutritional composition, the nutritional composition is added in an amount such that the casein phosphopeptide (CPP) content in the food product is between 0.01 and 2% by weight relative to the total weight of the food product; and/or
-when L-cystine is present in the nutritional composition, the nutritional composition is added in an amount such that the content by weight of L-cystine in the food product is between 0.01 and 0.8% relative to the total weight of the food product; and/or
-when L-phenylalanine is present in the nutritional composition, the nutritional composition is added in an amount such that the content by weight of L-phenylalanine in the food product is between 0.002 and 0.8% relative to the total weight of the food product; and/or
-when pantothenic acid is present in the nutritional composition, the nutritional composition is added in an amount such that the pantothenic acid content in the food is from 0.001% to 0.1% by weight, relative to the total weight of the food; and/or
-when biotin is present in the nutritional composition, the nutritional composition is added in an amount such that the content by weight of biotin in the food product is between 0.000001% and 0.0001% with respect to the total weight of the food product; and/or
-when sodium citrate is present in the nutritional composition, the nutritional composition is added in an amount such that the sodium citrate is present in the food product in an amount of 0.02-8% by weight relative to the total weight of the food product; and/or
-when potassium chloride is present in the nutritional composition, the nutritional composition is added in an amount such that the potassium chloride content in the food product is 0.02-8% by weight relative to the total weight of the food product.
10. Use of the nutritional composition according to claims 1-5 or the food product according to any one of claims 6-9 for non-therapeutic purposes in improving brain development and intelligence, in particular promoting neurological development, in infants and young children.
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| CN115843880A (en) * | 2022-11-29 | 2023-03-28 | 黑龙江飞鹤乳业有限公司 | Nutritional composition containing breast milk oligosaccharide and osteopontin, food and application |
| CN116671637A (en) * | 2023-07-25 | 2023-09-01 | 美维仕(北京)健康管理有限公司 | Nutritional composition, food and use |
Citations (2)
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|---|---|---|---|---|
| CN110074188A (en) * | 2019-05-16 | 2019-08-02 | 福建农林大学 | A kind of baby formula milk powder and preparation method thereof adding human milk oligosaccharides |
| CN112841317A (en) * | 2021-02-04 | 2021-05-28 | 合生元（广州）健康产品有限公司 | Nutritional composition suitable for infants fed by elderly puerperae |
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2022
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110074188A (en) * | 2019-05-16 | 2019-08-02 | 福建农林大学 | A kind of baby formula milk powder and preparation method thereof adding human milk oligosaccharides |
| CN112841317A (en) * | 2021-02-04 | 2021-05-28 | 合生元（广州）健康产品有限公司 | Nutritional composition suitable for infants fed by elderly puerperae |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115843880A (en) * | 2022-11-29 | 2023-03-28 | 黑龙江飞鹤乳业有限公司 | Nutritional composition containing breast milk oligosaccharide and osteopontin, food and application |
| CN116671637A (en) * | 2023-07-25 | 2023-09-01 | 美维仕(北京)健康管理有限公司 | Nutritional composition, food and use |
| CN116671637B (en) * | 2023-07-25 | 2023-10-27 | 美维仕(北京)健康管理有限公司 | Use of nutritional compositions |
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