CN115399480A - Nutrition composition containing pantothenic acid for promoting neural development and its preparation and application - Google Patents
Nutrition composition containing pantothenic acid for promoting neural development and its preparation and application Download PDFInfo
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- CN115399480A CN115399480A CN202210520202.3A CN202210520202A CN115399480A CN 115399480 A CN115399480 A CN 115399480A CN 202210520202 A CN202210520202 A CN 202210520202A CN 115399480 A CN115399480 A CN 115399480A
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- 238000007634 remodeling Methods 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- SQVRNKJHWKZAKO-OQPLDHBCSA-N sialic acid Chemical compound CC(=O)N[C@@H]1[C@@H](O)C[C@@](O)(C(O)=O)OC1[C@H](O)[C@H](O)CO SQVRNKJHWKZAKO-OQPLDHBCSA-N 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 235000019710 soybean protein Nutrition 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 235000020209 toddler milk formula Nutrition 0.000 description 1
- 235000009492 vitamin B5 Nutrition 0.000 description 1
- 239000011675 vitamin B5 Substances 0.000 description 1
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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
- A23L33/125—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives containing carbohydrate syrups; containing sugars; containing sugar alcohols; containing starch hydrolysates
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- A23C9/00—Milk preparations; Milk powder or milk powder preparations
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- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23C—DAIRY PRODUCTS, e.g. MILK, BUTTER OR CHEESE; MILK OR CHEESE SUBSTITUTES; MAKING THEREOF
- A23C9/00—Milk preparations; Milk powder or milk powder preparations
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- 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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- A23L33/17—Amino acids, peptides or proteins
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
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- A61K31/7016—Disaccharides, e.g. lactose, lactulose
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- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
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Abstract
A neurodevelopmental nutritional composition containing pantothenate is disclosed, the composition including 2' -fucosyllactose and osteopontin and pantothenate. The invention also discloses the preparation and application of the composition. The composition is effective in promoting nerve development.
Description
Technical Field
The invention relates to a pantothenic acid-containing neurodevelopment nutrient composition, and a preparation method and application thereof.
Background
Brain development is influenced by genetic and environmental factors. In the latter, maternal and early-life nutrition plays a key role in neurodevelopmental processes such as neuronal maturation, synaptogenesis and myelination. Myelination is the process by which Oligodendrocytes (OL) 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 generate an adult population of Oligodendrocytes (OLs). Post-mitotic OPC 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 OPC proliferation, OPC differentiation and maturation into myelinated OL, and myelination, is highly regulated by 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 of great importance to provide a composition which is capable of enhancing brain development and intelligence in infants and in particular promoting neural development such as neuronal maturation, synaptogenesis and myelination.
2 '-fucosyllactose (2' -FL) is a neutral fucosylated breast milk oligosaccharide (HMOs). It is helpful for the development of intestinal microorganisms and immune system of infants, and has antibacterial, antiviral and antiinflammatory effects, and can be used for preventing infection, relieving disease course, and promoting cognitive development of infants.
Osteopontin (OPN), which was originally found in bone, is also found in relatively high mass concentrations in human milk and is a highly glycosylated and phosphorylated acidic protein comprising an arginine-glycine-aspartic acid sequence. Many studies have demonstrated that OPN plays an important role in the organism, in particular in immune activation, bone injury repair, angiogenesis, skeletal remodeling, and in the promotion of brain development.
Pantothenic acid, also known as vitamin B5, is a peracid and is widely found in a variety of foods because of its acidic nature. Pantothenic acid is a compound consisting of pantoic acid and beta-alanine and has the molecular formula of C9H17O5N. Pantothenic acid is a light yellow sticky substance, is dissolved in water and acetic acid, is relatively stable to heat, oxidation and reduction in neutral solution, but is easily damaged by acid, alkali and dry heat (2-6 days) to be common pantothenic acid as a calcium salt, is a white powdery crystal, is slightly bitter, is soluble in water, is stable to light and air, and can be damaged by heating in an aqueous solution with the pH of 5-7. It has effects in promoting metabolism, promoting formation of hair, producing antibody, and maintaining hair nutrition.
Disclosure of Invention
The present invention was made in order to enhance the development and maturation of neonatal cognitive function.
As one aspect of the invention, a neurodevelopmental nutritional composition comprising pantothenic acid, said composition comprising 2' -fucosyllactose and osteopontin.
In at least one possible embodiment, the composition wherein the mass ratio of 2' -fucosyllactose to osteopontin is from 0.05 to 2000, preferably from 0.1 to 1000, further preferably from 1 to 100, further preferably from 5 to 50.
In at least one possible embodiment, the composition further comprises pantothenic acid. In a specific embodiment, the pantothenic acid is a derivative or combination thereof.
In at least one possible embodiment, the composition has a pantothenic acid content of not less than 0.001%, preferably not less than 0.01%, and more preferably not less than 0.1% by weight of the composition.
In at least one possible embodiment, the content ratio of 2' -fucosyllactose, pantothenic acid and osteopontin in the composition is from 0.01 to 2000, preferably from 0.01 to 1000, from 0.15 to 150, and further preferably from 0.1 to 100.
As another aspect of the invention, it relates to a method for preparing the above composition, mixing the 2' -fucosyllactose, pantothenic acid and casein.
As a further aspect of the invention, it relates to the use of the above composition for the preparation of a food product.
In at least one possible embodiment, the comestible is an infant comestible or a pregnant woman comestible. In at least one embodiment, the infant food is an infant formula.
As a further aspect of the invention, it relates to a food product comprising the above composition. The edible product is an infant edible product or a pregnant woman edible product. In at least one embodiment, the infant food product is an infant formula. In at least one embodiment, the 2' -fucosyllactose is present in the edible product in an amount of 0.04 to 4% by weight. In at least one embodiment, the osteopontin is present in an amount of 0.004 to 0.4% by weight of the food product.
As a further aspect of the invention, the invention relates to the use of the above composition for the preparation of a medicament for promoting the development of cognitive functions.
As a further aspect of the invention, it relates to the use of the above composition or the above food product for a non-therapeutic purpose in promoting the development of cognitive functions.
The nutritional composition for promoting the neural development provided by the embodiment of the invention can obviously promote the development of a nervous system, and all the contained components are conventional nutritional components.
Detailed Description
The new cognitive function in the present application includes new cognitive functions in any growth and development stages such as new cognitive function in fetal period and new cognitive function in infant period, and includes all cell and organic activities related to cognitive functions such as nerve cell growth and development, neuron maturation, synaptogenesis and myelination.
Edible items in this application include all items that can be consumed by animals and humans, including but not limited to food, food ingredients, beverages, drink ingredients, and the like.
Embodiments of the present invention will be described in detail below with reference to examples, but it will be understood by those skilled in the art that the following examples are only illustrative of the present invention and should not be construed as limiting the scope of the present invention. The examples, in which specific conditions are not specified, were conducted under conventional conditions or conditions recommended by the manufacturer. The reagents or instruments or methods used in the examples of the present invention are those which are not indicated as providing sources, and are all conventional products which are commercially available or are available from the applicant.
Based on the purpose of the invention of enhancing the development and maturation of the newborn cognitive function, the inventor of the present invention conducts screening and combination among raw materials which can be used for nutrition supply of newborn infants, and unexpectedly finds a nutritional composition having a significant enhancing effect on the development and maturation of the newborn cognitive function, which can be further applied to the preparation of various foods, health products, medicines, and the like. The processes of the present invention can be carried out by one of ordinary skill in the art based on the disclosure of the present application in combination with routine experimentation in the art.
The application claims priority of the chinese patent application No. 202111127689.0, which introduces the entire content of the priority document into the application and records part of the content of the priority text as follows:
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-on formulas and baby 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 the product by physical methods only. 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-on" refers to a liquid or powder product made by adding appropriate amounts of vitamins, minerals and/or other ingredients to a milk or milk protein product or soy protein product as the main raw material and producing the product by a physical process. Is suitable for older infants, and has energy and nutritional components capable of meeting partial nutritional requirements of older infants of 6-12 months old.
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 using a physical method. Is suitable for children, and has energy and nutrient 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 whose majority of nutrients and/or energy are derived from human breast milk.
The term "infant/follow-on/older infant/toddler fed primarily with infant formula" has a general meaning and refers to an infant or toddler whose source of nutrients and/or energy is primarily derived from physically produced 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.
The present inventors have surprisingly found that Osteopontin (OPN) and 2 '-fucosyllactose (2' -FL), when used in combination, synergistically promote neuronal maturation, synaptogenesis and myelination, and in particular, synergistically promote the proliferation, maturation and differentiation of OPC to mature OLs and/or the myelinating properties of OL.
In one embodiment, the nutritional composition consists of osteopontin and 2 '-fucosyllactose (2' -FL).
In one embodiment, osteopontin may be provided in or may be derived from: osteopontin protein powder, and/or whey powder containing osteopontin. 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, a 990.
When the mass ratio of 2 '-fucosyllactose (2' -FL) to osteopontin in the nutritional composition is within the above range, the synergistic effect in promoting neural development such as neuronal maturation, synaptogenesis and myelination, in particular promoting the myelination properties of OPC OLs and/or OL in proliferation, maturation and differentiation is more pronounced.
In one embodiment, the nutritional composition may optionally further comprise, in addition to 2 '-fucosyllactose (2' -FL) and osteopontin, 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; and
(3) 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.
1.1.
1.1 6500.
In one embodiment, the nutritional composition comprises casein phosphopeptides (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.
1.1.
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, when present, can be in the range of 0.0000025-0.025, preferably 0.0000125-0.0121, such as 0.0000025, 0.000005, 0.000010, 0.000015.
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) and osteopontin, especially when the mass ratio of the optional substance to osteopontin is within the above range, the synergistic effect in promoting neural development such as neuronal maturation, synaptogenesis and myelination, in particular promoting the proliferation, maturation and differentiation of OPC to mature OLs and/or the myelinating properties of OL is more pronounced.
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 may be in liquid form.
The food product of the invention may be an infant formula (e.g. infant formula, follow-on 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%, </xnotran> 7.20%, 7.25%, 7.30%, 7.35%, 7.40%, 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%, 10.95%, 10.45%, 10%, and any range or both of these values and any subrange or any subrange 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%, </xnotran> 0.745%, 0.750%, 0.755%, 0.760%, 0.765%, 0.770%, 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%, 1.995%, or any subrange therebetween, and any subrange or any subrange therebetween.
In one embodiment, the nutritional composition is added in an amount such that the 2 '-fucosyllactose (2' -FL) is present in an amount of 0.04-4% by weight and osteopontin is present in an amount of 0.004-0.4% by weight, relative to the total weight of the food product.
When the contents of 2' -fucosyllactose and osteopontin in the food are within the above ranges, it is possible to remarkably promote neuronal maturation, synaptogenesis, myelination and other neural developments while balancing various nutrients, and in particular, it is possible to promote the proliferation, maturation and differentiation of OPC into mature OLs and/or the myelination property of OL.
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 β -glucan is present in the nutritional composition, the nutritional composition may be added in an amount such that the weight content of yeast β -glucan in the food product is 0.001-2.5%, 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%, 1.60%, 1.65%, 1.70%, 1.75%, 1.80%, 1.90%, 1.95%, 1.00%, 1.05%, 1.50%, 1.5%, 1.45%, 1.50%, 1.5%, 2.45%, 2.5%, 2.0.0.0.0.0.0.0%, 2.0.0.0.5%, 1.0%, 1.0.5%, 1.35%, 2.35%, 1.0.5%, 1.35%, 1.0.5%, 2.35%, 2.75%, 2.0%, 2.35%, 2.0.0.0%, 2.5%, 2.0.5%, 2.35%, 2.0%, 2.95%, 2.75%, 2.95%, 2.0%, 2.75%, or any of the stated value.
<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%, </xnotran> 22.0%, 22.5%, 23.0%, 23.5%, 24.0%, 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, as well as any values and subranges subsumed therein.
In one embodiment, 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 by weight in the food product may be between 0.01 and 2% 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 any range defined by any two thereof and any values or subranges subsumed therein.
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 product, relative to the total weight of the food product, can be 0.001% to 0.1%, 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, relative to the total weight of the food product, can be 0.000001% -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 any range defined by both and including any range subsumed therein.
<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 synergistic effect in promoting nerve development such as neuron maturation, synaptogenesis and myelination, particularly in promoting proliferation, maturation and differentiation of OPC into mature OLs and/or OL myelination property is more remarkable.
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, e.g. milk powder.
In another aspect, the invention relates to the use of the above nutritional composition or the above food product for non-therapeutic purposes in improving brain development and intelligence, in particular in promoting neurological development (e.g. promoting the proliferation, maturation and differentiation of OPC to mature OLs and/or OL) in infants and young children.
Examples
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 weight
Osteopontin: the osteopontin powder Lacprodan OPN-10 of the groups P/S of Arla Foods, denmark, with an osteopontin content of 95.6% by weight
In the following sections, 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) and osteopontin as active ingredients, and the ratio refers to the mass ratio between 2 '-fucosyllactose (2' -FL) and osteopontin as active ingredients.
Various nutritional compositions were prepared by mixing 2 '-fucosyllactose (2' -FL) raw material and Osteopontin (OPN) raw material in the proportions shown in the examples below, 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 nutrient mixtures on myelination and neurons. Through experimental study on the influence of components containing 2' -FL and OPN in different proportions on the development of brain nerve cells, the method systematically and intuitively evaluates the influence on the development of early brain and has profound significance for guiding the application of the two components.
1 materials and methods
1.1 instruments 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 neurons and OLs primary mixed 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 for 10 minutes at 4 ℃ 515 g.
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 ℃ and 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 (nutrient composition containing 2' -FL 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, MAB312 RX) for 2h at room temperature, followed by incubation with neurofilament antibodies (dilution: 1/500, sigma, N4142) for 2h at room temperature. And finally, co-incubating for 1h at room temperature by using a secondary goat anti-rabbit antibody (dilution 1/400, SIGMA, SAB 4600084).
At 18DIV, neural cells were incubated with mouse monoclonal antibody MAG (dilution: 1/400, millipore, MAB 1567) and neurofilamin antibody (dilution: 1/500, sigma, N4142) for 2h. 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, NBP 1-05204) and neurofilament 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-fold 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 quantifying the number of A2B 5-expressing cells under 12DIV conditions and the results were expressed as the average number of A2B 5-expressing cells per well per graph.
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 maturity of MAG-positive cells was assessed by measuring the average surface area of MAG-positive cells in 18DIV wells (μm/map/well).
The degree of maturation of OLs was estimated by calculating 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, positive control and sample intervention groups were compared, respectively, with Olesoxime (300 nM, demonstrated to accelerate OLs maturation and myelination in vitro and in vivo) as positive controls. Immunohistochemistry (MBP, NF, A2B 5) measures the effect of OPN and 2FL 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 doses of cells
1.4 statistical analysis
The results are expressed as mean ± standard error (mean ± SEM), and the SPSS software used for T-test and one-way ANOVA test was judged to have significant difference when p < 0.05.
2 results of the experiment
2.1 Effect of Each sample on nerve cells
To measure the effect of mixed nutrition or single nutrition treatments on OPCs, we assessed the number of labeled A2B5 positive cells after 12DIV to estimate the number of OPCs.
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 and/or OPN on the number of A2B5 positive cells.
The sample processing results showed that the 2' -FL high dose, OPN high dose group significantly increased the number of A2B5 positive cells compared to the blank control group, indicating that both components contribute to the proliferation of oligodendrocyte precursor cells.
In addition, the 2' -FL and OPN doses used in cell experiment example 9 (corresponding to example 1) were the same as those used in cell experiment examples 3 and 4 (corresponding to comparative examples 1 and 2), respectively. As can be seen from the above table, cellular experiment example 3 and cellular experiment example 4 increased the number of A2B5 positive cells by 23.334 and 19.834, respectively, relative to cellular experiment example 1 (corresponding to the blank control), while cellular experiment example 9 increased the number of A2B5 positive cells by 47.834, which is greater than the sum of the former two (23.334 +19.834= 43.168), relative to cellular experiment example 1, indicating that there is a synergistic effect between 2' -FL and OPN, which can synergistically increase the number of A2B5 positive cells.
2.2 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.
The average number of MBP-positive cells measured per picture and per well is shown in table 4.
TABLE 4 Effect of different nutritional composition samples containing 2' -FL and/or OPN on the number of MBP positive cells.
As can be seen from table 4, the positive control, olesoxime, showed an increased number of MBP-positive cells compared to the blank control group; the high dose 2' -FL, high dose OPN group significantly increased the number of MBP positive cells, suggesting that both components contribute to the maturation of oligodendrocyte precursor cells.
In addition, as can be seen from the above table, cellular experimental example 3 and cellular experimental example 4 (corresponding to comparative examples 1 and 2, respectively) increased the number of MBP positive cells by 34.667 and 28.834, respectively, relative to cellular experimental example 1 (corresponding to blank control), while cellular experimental example 9 (corresponding to example 1) increased the number of MBP positive cells by 84.167, which is greater than the sum of the two (34.667 +28.834= 63.501), relative to cellular experimental example 1, indicating that there is a synergistic effect between 2' -FL and OPN, which can synergistically increase the number of MBP positive cells.
The invention provides a research on the brain development of Osteopontin (OPN) and 2 '-fucosyllactose (2' -FL) compositions, and provides a new idea for the development of future functional foods. Osteopontin and 2 '-fucosyllactose (2' -FL) are capable of promoting the proliferation, maturation and differentiation of OPCs into mature OLs and/or the myelinating properties of the OL during early brain development. Has wide prospect in the aspects of neuron development and brain development.
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 with osteopontin concentrated whey protein powder (osteopontin 5.2%): arla Foods Ingredients Group P/S, denmark
2 '-fucosyllactose (96.0% 2' -fucosyllactose): glyCare TM 2FL 9000
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: dismaman 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, 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, 38.5 parts of osteopontin-rich concentrated whey protein (5.2 percent of osteopontin in each part), 20.8 parts of 2 '-fucosyllactose (96.0 percent of 2' -fucosyllactose in each part), 350 parts of desalted whey powder, 117 parts of lactose, 83.7 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 uniformly, pasteurizing, homogenizing, evaporating for concentration, spray drying to obtain powdery semi-finished product, and packaging the uniformly mixed milk powder with nitrogen to obtain the final product. The content of 2' -fucosyllactose in the product is 2 percent, and the content of osteopontin is 0.2 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 (5.2 percent of osteopontin in each part), 4.2 parts of 2 '-fucosyllactose (96.0 percent of 2' -fucosyllactose in each part), 350 parts of desalted whey powder, 175 parts of lactose, 85.1 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 and 0.04% of osteopontin.
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, 10.42 parts of 2 '-fucosyllactose (96.0% of 2' -fucosyllactose in each part), 1.05 parts of osteopontin-rich concentrated whey protein powder (95.6% of osteopontin in each part), 350 parts of desalted whey powder, 48 parts of lactose, 73.53 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 uniformly, pasteurizing, homogenizing, evaporating for concentration, spray drying to obtain powdery semi-finished product, and nitrogen-filling and packaging the uniformly mixed milk powder to obtain the final product. The content of 2' -fucosyllactose in the product is 1 percent, and the content of osteopontin is 0.1 percent.
Application example 4
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 (5.2 parts of osteopontin in each part), 2.08 parts of 2 '-fucosyllactose (96.0 parts of 2' -fucosyllactose in each part), 350 parts of desalted whey powder, 48 parts of lactose, 79.07 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 uniformly, pasteurizing, homogenizing, evaporating for concentration, spray drying to obtain powdery semi-finished product, and nitrogen-filling and packaging the uniformly mixed milk powder to obtain the final product. The content of 2' -fucosyllactose in the product is 0.2%, and the content of osteopontin is 0.02%.
Application example 5
The modified milk powder containing 2' -fucosyllactose and osteopontin is suitable for middle-aged and elderly people, and each 1000 parts of modified milk powder is prepared from the following components in parts by weight:
the milk powder of the invention uses the following raw materials: 750 parts of whole milk powder, 4.18 parts of osteopontin powder (each part contains osteopontin 95.6%), 195 parts of solid corn syrup, 46.4 parts of fructo-oligosaccharide, 0.42 part of 2 '-fucosyl lactose (each part contains 2' -fucosyl lactose 96.0%), 3 parts of compound vitamin and 1 part of compound mineral substance; 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 0.04% of 2' -fucosyllactose and 0.4% of osteopontin.
Application example 6
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), 350 parts of skimmed milk powder, 74.8 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%, and the content of osteopontin is 0.004%.
Application example 7
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 944.35 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), 9.3 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 content of 2' -fucosyllactose in the product is 4 percent, and the content of osteopontin is 0.4 percent.
Application example 8
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 941.49 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), 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 content of 2' -fucosyllactose in the product is 4 percent, and the osteopontin is 0.004 percent.
Based on the contents described in the priority application, the inventors conducted further experiments as follows.
The protocol for the combination of 2' -FL and OPN was not repeated in the following section. The inventors directly refer to the results of the experiments described in the priority text in performing data analysis.
The following experimental section and the experimental section described in the priority application are two separate sections, with the experimental groupings and the results display charts encoded separately.
The present invention uses an in vitro model of primary cell culture containing neurons and OLs to evaluate the effect of a breast milk oligosaccharide composition on myelination. Mixed nutrients are added to mixed cell cultures to promote proliferation, maturation and differentiation of OPC into mature OLs and/or the myelinating properties of OLs. OPC density was first assessed after 12d in vitro culture. The level of OPC differentiation into OL and OL maturation was then assessed by quantifying MAG-positive cells and MBP-positive cells at 18 days and 30 days, respectively. Finally, the level of myelination after 18 and 30d cell culture was further assessed.
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), osteopontin (OPN), and pantothenic acid as active ingredients, and the ratios refer to mass ratios between 2 '-fucosyllactose (2' -FL), osteopontin (OPN), and pantothenic acid as active ingredients.
A2B5 is an oligodendrocyte marker.
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 percentage 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 OL to support myelination.
MBP is strongly expressed in mature myelinated OL 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 adhesive reticulins, which correlates with maturation of the OL.
In the examples of the present invention, 2' -fucosyllactose was replaced with GlyCare TM 2FL 9000 (content of 2' -FL 96.0%).
In the examples of the present invention, osteopontin was added in the form of Arla Foods Ingredients Group P/S, lacprodan OPN-10 (OPN content 95.6%).
In the examples of the present invention, pantothenic acid is added in the form of vitamin complexes from Dismann.
At present, the research on the brain development is limited to the research on 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 nutrient mixtures on myelination and neurons. Through experimental study on the influence of components containing 2' -FL, osteopontin and pantothenic acid in different proportions on the development of brain nerve cells, the method systematically and intuitively evaluates the influence on the early brain development and has profound significance for guiding the application of the composition.
1 materials and methods
1.1 instruments and reagent consumables
Cell culture box, laser confocal fluorescence microscope, centrifuge, electronic balance, vortex instrument, water bath pot, tissue homogenizer.
Nerve 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 mixed neuronal and OL primary 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. Subsequently, cell culture medium DMEM (PAN BIOTECH) containing DNase (0.1 mg/ml, PAN BIOTECH) and 10% fetal bovine serum (GIBCO) was added to terminate the trypsin action. The 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 48-well plates (20000/well) pre-coated with poly-L-lysine (BD Falcon) and laminin (Sigma). The growth 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 48-well plates were kept in humidified incubator at 37 ℃ and ambient air (95%) -CO 2 (5％)。
1.2.2 neural cell culture
Starting cells were of the same number, incubated in 48-well plates for 12, 18 or 30d in vitro experiments, half of the culture medium was changed every other day, and fresh medium was supplemented with the nutrient composition containing 2' -FL, OPN and/or pantothenic acid prepared in the examples of the present invention.
1.2.3 immunohistochemical experiments
12. After 18 and 30d in vitro culture, 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.
In 12d in vitro cultures, neural cells were incubated with the mouse monoclonal antibody A2B5 (dilution: 1/200, millipore, MAB312 RX) for 2h at room temperature, followed by incubation with the neurofilamin antibody (dilution: 1/500, sigma, N4142) for 2h at room temperature. And finally, co-incubating for 1h at room temperature by using a secondary goat anti-rabbit antibody (dilution 1/400, SIGMA, SAB 4600084).
In 18d in vitro cultures, neural cells were incubated for 2h with the mouse monoclonal antibody MAG (dilution: 1/400, millipore, MAB 1567) and the neurofilamin antibody (dilution: 1/500, sigma, N4142). Then incubated with secondary goat anti-rabbit antibody (dilution: 1/400, sigma, SAB4600042) and secondary goat anti-rabbit antibody (dilution: 1/400, SIGMA, SAB4600084) for 1h at room temperature.
In 30d in vitro cultures, neural cells were incubated with the mouse monoclonal antibody MBP (dilution: 1/1000, novus, NBP 1-05204) and the neurofilament 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-fold 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 quantifying the number of A2B 5-expressing cells under in vitro culture conditions of 12d and the results were expressed as the average number of A2B 5-expressing cells per well per graph.
Differentiation of OPCs into OLs was assessed by counting the number of MAG positive cells in cell culture. Results are expressed as the average number of cells per well.
At 30d, the degree of maturation of OLs was estimated by counting the number of MBP-positive cells (average number of cells per well per picture).
1.3 cell assay grouping
The prepared cells were seeded on 48-well plates and cultured for a fixed period of time, half of the culture medium was replaced every other day, and different concentrations of the test reagents (12, 18, 30d added, respectively) were added to fresh primary cell culture medium, 6 replicates per sample. Blank, positive and experimental groups (comparative and examples) were compared, respectively, with the positive control, olesoxime (300 nM) demonstrated to accelerate OLs maturation and myelination in vitro and in vivo. Immunohistochemistry measured the effect of OPN and 2FL, pantothenic acid, alone or in combination, on OPC populations, OL maturation and differentiation, myelin formation and neurite outgrowth. The specific experimental doses are given in table 1 below (final concentrations).
Table 1: dose for cell experiments
1.4 statistical analysis
Results are expressed as mean ± standard error (mean ± SEM), and the T-test and one-way ANOVA test using SPSS software was judged to be significantly different when p < 0.05.
2 results of the experiment
To measure the effect of the added reagent on OPC, the number of labeled A2B5 positive cells after 12d in vitro culture was evaluated to estimate the number of OPCs. The average number of A2B5 positive cells measured per well is presented in table 2.
Table 2: effect of reagent addition on the number of A2B 5-Positive cells
Sample treatment results show that both 2' -FL and OPN can significantly increase the number of A2B5 positive cells compared to the blank control group, and it appears that both components contribute to the proliferation of oligodendrocyte precursor cells. Pantothenic acid can obviously increase the number of A2B5 positive cells after being mixed with 2-FL and OPN.
Effect of added Agents on OPC cell myelination
To measure the effect of the added agent on the myelination of OPC cells, the number of positive cells labeled MAG after 18d in vitro culture was evaluated. The average number of MAG-positive cells measured per well is shown in Table 3.
Table 3: effect of reagent addition on the number of MAG-positive cells
Both 2' -FL and OPN significantly increased the number of MAG positive cells compared to the blank control group, and both components appeared to contribute to myelination of oligodendrocyte precursor cells. Pantothenate, when mixed with 2-FL and OPN, significantly increased the number of MAG positive cells, indicating a synergistic effect of the combination.
Effect of Agents addition on OPC cell maturation
To measure the effect of the added reagent on the maturation of OPCs, the number of positive cells labeled MBP after 30d in vitro culture was evaluated. The average number of MBP-positive cells measured per well is shown in table 4.
Table 4.: effect of reagent addition on the number of MBP-Positive cells
Both 2-FL and OPN significantly increased the number of MBP-positive cells, suggesting that both components contribute to the maturation of oligodendrocyte precursor cells. Pantothenic acid mixed with 2-FL and OPN can obviously increase the number of MBP positive cells, and the combination has synergistic effect
The above-mentioned embodiments are merely preferred embodiments for fully illustrating the present invention, and the scope of the present invention is not limited thereto. The equivalent substitution or change made by the technical personnel in the technical field on the basis of the invention is all within the protection scope of the invention. The protection scope of the invention is subject to the claims.
Claims (17)
1. A neurodevelopmental nutritional composition comprising pantothenate, wherein said composition comprises 2' -fucosyllactose and osteopontin and pantothenate.
2. The composition according to claim 1, wherein the mass ratio of 2' -fucosyllactose to osteopontin in the composition is from 0.05 to 2000, preferably from 0.1 to 1000, further preferably from 1 to 100, further preferably from 5 to 50, and most preferably from 10 to 20.
3. The composition of claim 2, wherein the composition comprises pantothenic acid in an amount of no less than 0.001%, preferably no less than 0.01%, and more preferably no less than 0.1% by weight of the composition.
4. The composition of claim 3, wherein the ratio of the contents of 2' -fucosyllactose, pantothenic acid and osteopontin in the composition is 0.01 to 2000.
5. Process for the preparation of a composition according to any one of claims 1 to 4, characterized in that the 2' -fucosyllactose, osteopontin and pantothenic acid are mixed.
6. Use of a composition according to any one of claims 1 to 4 for the preparation of a food product.
7. The use of claim 6, wherein the food product is an infant food product.
8. The use of claim 6, wherein said infant food product is an infant formula.
9. The use of claim 6, wherein the consumable is a consumable for a pregnant woman.
10. A food product comprising the composition of any one of claims 1 to 4.
11. The food product of claim 10, wherein the food product is an infant food product.
12. The food product of claim 10, wherein said infant food product is an infant formula.
13. The consumable of claim 10, wherein the consumable is a consumable for a pregnant woman.
14. The edible product of any one of claims 10 to 13, wherein the 2' -fucosyllactose is present in the edible product in an amount of from 0.04 to 4% by weight.
15. The food product of claim 14, wherein the osteopontin is present in the food product in an amount of 0.004 to 0.4% by weight.
16. Use of a composition according to any one of claims 1 to 4 for the manufacture of a medicament for promoting the development of cognitive functions.
17. Use of a composition according to any one of claims 1 to 4 or a food product according to any one of claims 10 to 15 for a non-therapeutic purpose in promoting the development of cognitive functions.
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