CN116268412A - Neural development promoting nutritional composition containing yeast beta-glucan and preparation and application thereof - Google Patents
Neural development promoting nutritional composition containing yeast beta-glucan and preparation and application thereof Download PDFInfo
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- CN116268412A CN116268412A CN202211090064.6A CN202211090064A CN116268412A CN 116268412 A CN116268412 A CN 116268412A CN 202211090064 A CN202211090064 A CN 202211090064A CN 116268412 A CN116268412 A CN 116268412A
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- osteopontin
- fucosyllactose
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- 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
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- A23C9/00—Milk preparations; Milk powder or milk powder preparations
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- 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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- 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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Abstract
The invention discloses a neural development promoting nutritional composition containing yeast beta-glucan, which comprises 2' -fucosyllactose, osteopontin and yeast beta-glucan. 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 nutritional composition containing yeast beta-glucan for promoting neural development, and preparation and application thereof.
Background
The development of the brain is affected by genetic and environmental factors. In the latter, maternal and early life nutrition plays a critical role in neuronal maturation, synaptogenesis and myelination, among other neurological processes. Myelination is the process by which Oligodendrocytes (OL) of the Central Nervous System (CNS) myelinate around axons, which is critical for normal brain connections. For humans, myelination begins in the middle of gestation and peaks in the first few years of life. Environmental factors may affect myelination in human brain development. In particular, different nutrients exhibit 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 (OPC) migrate from within the cortex and produce an adult population of Oligodendrocytes (OL). Post-mitotic OPC differentiates into myelinated OLs which expand many processes, establishing contact with axons of different neurons, initiating myelination, which enhances neuronal connectivity and supports maturation of neonatal cognitive functions.
In the central nervous system, each step of myelination, including proliferation of OPC, differentiation and maturation of OPC into myelinated OL, and myelination, is highly regulated by external and internal factors. In particular, the effects of different nutrients on myelination are different, suggesting that early life nutrition may have a significant impact on the regulation of myelination. Thus, identification of early life nutritional factors that support myelination is critical for optimal brain and cognitive development. It is of great importance to provide a composition which can improve brain development and intelligence in infants, in particular, promote neural development such as neuronal maturation, synaptogenesis, myelination and the like.
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, has antibacterial, antiviral and antiinflammatory effects, can prevent many infections and relieve disease course, and also has the functions of promoting cognitive development of infants.
Osteopontin (OPN), which was originally found in bone and is also a relatively high mass concentration in human milk, is a highly glycosylated and phosphorylated acidic protein comprising an arginine-glycine-aspartic acid sequence. Many studies have demonstrated that OPN has important roles in organisms, in particular in immune activation, bone injury repair, revascularization, bone remodeling, promotion of brain development.
Yeast beta-glucan, also known as dextran, is a polysaccharide. The immune factor can be specifically combined with macrophages to excite and activate the immune factor, so that the abnormal cells can be better removed, the invasion of external viruses can be prevented, and the effect of immunity can be achieved. The yeast beta-glucan has the functions of enhancing immunity, regulating blood fat, resisting radiation, reducing blood sugar, maintaining intestinal flora and the like. The beta-glucan can act on sub-health state of human body, promote the conversion of the beta-glucan to the health state, achieve the purpose of promoting health, and is suitable for people of all ages.
Disclosure of Invention
The present invention has been made in order to enhance the development and maturation of neonatal cognitive functions.
As one aspect of the invention, a neurodevelopmental nutritional composition comprising yeast beta-glucan is provided, the composition comprising 2' -fucosyllactose and osteopontin.
In at least one possible embodiment, the composition wherein the mass ratio of 2' -fucosyllactose to osteopontin is 0.05-2000:1, preferably 0.1-1000:1, further preferably 1-100:1, still further preferably 5-50:1, most preferably 10-20:1.
In at least one possible embodiment, the composition further comprises yeast beta-glucan. In specific embodiments, the yeast β -glucan is a derivative thereof or a combination thereof.
In at least one possible embodiment, the yeast beta-glucan in the composition comprises not less than 0.001%, preferably not less than 0.1%, more preferably not less than 1%, even more preferably not less than 2.5% by mass of the composition.
In at least one possible embodiment, the composition comprises 2' -fucosyllactose, yeast β -glucan and osteopontin in a ratio of 0.01-2000:0.015-150:1, preferably 0.01-1000:0.15-150:1, further preferably 0.1-100:1.5-150:1.
As another aspect of the present invention, it relates to a method for preparing the above composition, mixing the 2' -fucosyllactose, yeast beta-glucan and casein.
As another 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 food product is an infant food product or a maternal food product. In at least one embodiment, the infant food is infant formula.
As a further aspect of the present invention, it relates to an edible product comprising the above composition. The edible product refers to infant food or pregnant woman food. In at least one embodiment, the infant food is infant formula. In at least one embodiment, the 2' -fucosyllactose is present in the food product in an amount of 0.04-4% by weight. In at least one embodiment, the osteopontin is present in the food product in an amount of 0.004-0.4% by weight.
As a further aspect of the invention, it relates to the use of the above composition for the preparation of a medicament for promoting the development of cognitive functions.
In a further aspect, the present invention relates to the use of the above composition or the above edible product for non-therapeutic purposes in promoting the development of cognitive functions.
The nutrition composition for promoting the neural development provided by the embodiment of the invention can obviously promote the development of a nervous system, and the contained components are all conventional nutrition components.
Detailed Description
The neonatal cognitive function in the application comprises neonatal cognitive function in any growth and development stage such as neonatal cognitive function in fetal period, neonatal cognitive function in infant period and the like, and comprises all cell and cytoplasmic activities related to the cognitive function such as nerve cell growth and development, neuron maturation, synapse generation, myelination and the like.
Edible products in this application include all items that are edible to animals and humans, including but not limited to food products, food ingredients, drinks, 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 for illustrating the present invention and should not be construed as limiting the scope of the present invention. The specific conditions are not noted in the examples and are carried out according to conventional conditions or conditions recommended by the manufacturer. The reagents or apparatus or methods used in the examples of the invention, the instruction not specifying the source of the supply, are all conventional products commercially available or available from the applicant.
Based on the object of the invention of enhancing the development and maturation of neonatal cognitive function, the inventors of the present invention have found unexpectedly a nutritional composition having a remarkable enhancing effect on the development and maturation of neonatal cognitive function by screening and combining raw materials usable for neonatal nutrition supply, which can be further applied to the preparation of various foods or health products or medicines, etc. Based on the disclosure of this application, one of ordinary skill in the art can implement the process of the present invention in combination with conventional experimental means in the art.
The present application claims the priority of the chinese patent application No. 202111127689.0, which incorporates the entire content of the priority document, and describes part of the content of the priority document as follows:
the term "infant" refers to a person from 0 to 6 months of age.
The term "older infant" refers to a person of 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, older infant formulas, and toddler formulas. Typically, infant formulas are used as a breast milk substitute from the birth of the infant, and older infant formulas are used as breast milk substitutes from 6 to 12 months after the birth of the infant, and toddler formulas are used as breast milk substitutes from 12 to 36 months after the birth of the infant.
The term "infant formula" refers to a liquid or powder product produced by physical means only, using milk and milk protein products or soy and soy protein products as the main raw material, adding appropriate amounts of vitamins, minerals and/or other ingredients. Is suitable for normal infants, and the energy and nutrient components of the infant formula can meet the normal nutritional requirements of infants in 0-6 months.
The term "infant formula" refers to liquid or powder products made from milk and dairy products or soy and soy protein products as the main raw material, with the addition of appropriate amounts of vitamins, minerals and/or other ingredients, and by physical means only. Is suitable for older infants, and the energy and nutrient components of the older infants can meet the partial nutrient requirements of older infants in 6-12 months.
The term "infant formula" refers to a liquid or powder product which is produced by using milk and milk protein products or soybean and soybean protein products as main raw materials, adding proper amount of vitamins, minerals and/or other ingredients, and producing and processing by using only a physical method. Is suitable for infants, and the energy and nutrient components of the infant feed can meet the partial nutritional requirements of the infants in 12-36 months.
The term "breast milk" is understood to mean the mother's breast milk or colostrum.
The term "completely breast-fed infant or young child" has its ordinary meaning and refers to infants whose vast majority of nutrients and/or energy is derived from human breast milk.
The term "infant/follow-up/toddler fed mainly with infant formula" has its usual meaning, meaning that the source of nutrition for nutrients and/or energy is mainly derived from infants or toddlers physically produced and processed into infant formula, follow-up or growing-up milk. The term "primarily" refers to at least 50%, such as at least 75%, of those nutrients and/or energy.
The inventors have surprisingly found that Osteopontin (OPN) and 2 '-fucosyllactose (2' -FL) when used in combination are capable of synergistically promoting neuronal maturation, synaptogenesis and myelination, and in particular synergistically promoting proliferation, maturation and differentiation of OPC into mature OLs and/or OL myelination properties.
In one embodiment, the nutritional composition consists of osteopontin and 2 '-fucosyllactose (2' -FL).
In one embodiment, osteopontin may be provided in the following form 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 content of osteopontin in the osteopontin-containing whey powder may be generally 2 to 30% by weight.
In one embodiment, 2 '-fucosyllactose (2' -FL) may be provided in the following source form: natural sources, and/or synthetic sources, and/or bacterial fermentation sources. The 2' -fucosyllactose content of each source may typically be 60-99.9%.
In one embodiment, the mass ratio of 2 '-fucosyllactose (2' -FL) to osteopontin in the nutritional composition may be in the range of 0.05-2000:1, preferably 0.1-1000:1, preferably 1-100:1, preferably 5-50:1, preferably 10-20:1, for example, it may be 0.05:1, 0.1:1, 0.2:1, 0.3:1, 0.4:1, 0.5:1, 0.6:1, 0.7:1, 0.8:1, 0.9:1, 1:1, 1.5:1, 2:1, 2.5:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, 10:1, 11:1, 12:1, 13:1, 14:1, 15:1, 16:1, 17:1, 18:1, 19:1, 20:1, 21:1, 22:1, 23:1, 24:1, 25:1, 26:1, 27:1, 28:1, 29:1, 30:1, 31:1, 32:1, 33:1, 34:1, 35:1, 36:1, 37:1, 38:1, 39:1, 42:1, 41:1). 43:1, 44:1, 45:1, 46:1, 47:1, 48:1, 49:1, 50:1, 51:1, 52:1, 53:1, 54:1, 55:1, 56:1, 57:1, 58:1, 59:1, 60:1, 61:1, 62:1, 63:1, 64:1, 65:1, 66:1, 67:1, 68:1, 69:1, 70:1, 71:1, 72:1, 73:1, 74:1, 75:1, 76:1, 77:1, 78:1, 79:1, 80:1, 81:1, 82:1, 83:1, 84:1, 85:1, 86:1, 87:1, 88:1, 89:1, 90:1, 91:1, 92:1, 93:1, 94:1, 95:1, 96:1, 97:1, 98:1 }. 43:1, 44:1, 45:1, 46:1, 47:1, 48:1, 49:1, 50:1, 51:1, 52:1, 53:1, 54:1, 55:1, 56:1, 57:1, 58:1, 59:1, 60:1, 61:1, 62:1, 63:1, 64:1, 65:1, 66:1, 67:1, 68:1, 69:1, 70:1: 71:1, 72:1, 73:1, 74:1, 75:1, 76:1, 77:1, 78:1, 79:1, 80:1, 81:1, 82:1, 83:1, 84:1, 85:1, 86:1, 87:1, 88:1, 89:1, 90:1, 91:1, 92:1, 93:1, 94:1, 95:1, 96:1, 97:1, 98:1 1800:1, 1900:1, 2000:1, or a range defined by any two thereof, and any values and subranges subsumed within the range.
When the amount of 2 '-fucosyllactose (2' -FL) in the nutritional composition is more pronounced than in the above-mentioned range, the synergistic effect in promoting neuronal maturation, synaptogenesis and myelination, etc. neural development, in particular in promoting proliferation, maturation and differentiation of OPC into mature OLs and/or OL myelination properties is more pronounced.
In one embodiment, the nutritional composition may optionally further comprise, in addition to 2 '-fucosyllactose (2' -FL) and osteopontin:
-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
-a mineral 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
-a mineral 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.
In one embodiment, when yeast beta-glucan is present, its mass ratio to osteopontin may be in the range of 0.0025-625:1, preferably 0.1-15:1, for example, 0.0025:1, 0.005:1, 0.01:1, 0.02:1, 0.03:1, 0.04:1, 0.05:1, 0.06:1, 0.07:1, 0.08:1, 0.09:1, 0.10:1, 0.15:1, 0.20:1, 0.25:1, 0.30:1, 0.40:1, 0.50:1, 0.60:1, 0.70:1, 0.80:1, 0.90:1, 1.0:1, 1.5:1, 2.0:1, 2.5:1, 3.0:1, 4.0:1, 5.0:1, 6.0:1, 7.0:1, 8.0:1, 9.0:1, 10.0:1, 11.0:1, 12.0:1, 13.0:1, 14.0:1, 15:1, 16:1, 0.1, 0:1, 18:1, 0.1, 0:1, 0.1, 20:1, 0.1, 0:1.20:1, 0.1, 0:1); 23.0:1, 24.0:1, 25.0:1, 26.0:1, 27.0:1, 28.0:1, 29.0:1, 30.0:1, 31.0:1, 32.0:1, 33.0:1, 34.0:1, 35.0:1, 36.0:1, 37.0:1, 38.0:1, 39.0:1, 40.0:1, 41.0:1, 42.0:1, 43.0:1, 44.0:1, 45.0:1, 46.0:1, 47.0:1, 48.0:1, 49.0:1, 50.0:1, 51.0:1, 52.0:1, 53.0:1, 54.0:1, 55.0:1, 56.0:1, 57.0:1, 58.0:1, 59.0:1, 60.0:1, 61.0:1, 62.0:1, 63.0:1, 68:1, 68.0:1, 65.0:1, and 1; 23.0:1, 24.0:1, 25.0:1, 26.0:1, 27.0:1, 28.0:1, 29.0:1, 30.0:1, 31.0:1, 32.0:1, 33.0:1, 34.0:1, 35.0:1, 36.0:1, 37.0:1, 38.0:1, 39.0:1, 40.0:1, 41.0:1, 42.0:1, 43.0:1, 44.0:1, 45.0:1, 33.0:1, 38.0:1, 39.0:1, 40.0:1, 41.0:1, 42.0:1, 44.0:1, 45.0:1 46.0:1, 47.0:1, 48.0:1, 49.0:1, 50.0:1, 51.0:1, 52.0:1, 53.0:1, 54.0:1, 55.0:1, 56.0:1, 57.0:1, 58.0:1, 59.0:1, 60.0:1, 61.0:1, 62.0:1, 63.0:1, 64.0:1, 65.0:1, 66.0:1, 67.0:1, 68.0:1, and.
For example, the first and second embodiments of the present invention may be configured to Or a range defined by any two thereof, and any values and subranges subsumed within the range.
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.
In one embodiment, when casein phosphopeptide (CPP) is present, the mass ratio to osteopontin may be 0.025 to 500:1, preferably 0.025 to 55:1, for example 0.025:1, 0.03:1, 0.04:1, 0.05:1, 0.06:1, 0.07:1, 0.08:1, 0.09:1, 0.10:1, 0.15:1, 0.20:1, 0.25:1, 0.30:1, 0.40:1, 0.50:1, 0.60:1, 0.70:1, 0.80:1, 0.90:1, 1.0:1, 1.5:1, 2.0:1, 2.5:1, 3.0:1, 4.0:1, 5.0:1, 6.0:1, 7.0:1, 8.0:1, 9.0:1, 10.0:1, 11.0:1, 12.0:1, 13.0:1, 14.0:1, 15.0:1, 16.0:1, 17.0:1, 18.0:1, 19.0:1, 20:1, 0:1, 20.0:1, 0:1, 0.22:1, 0.1, 0:1, 0.0:1, 0.0.0:1). 23.0:1, 24.0:1, 25.0:1, 26.0:1, 27.0:1, 28.0:1, 29.0:1, 30.0:1, 31.0:1, 32.0:1, 33.0:1, 34.0:1, 35.0:1, 36.0:1, 37.0:1, 38.0:1, 39.0:1, 40.0:1, 41.0:1, 42.0:1, 43.0:1, 44.0:1, 45.0:1, 46.0:1, 47.0:1, 48.0:1, 49.0:1, 50.0:1, 51.0:1, 52.0:1, 53.0:1, 54.0:1, 55.0:1, 56.0:1, 57.0:1, 58.0:1, 59.0:1, 60.0:1, 61.0:1, 62.0:1, 63.0:1). 23.0:1, 24.0:1, 25.0:1, 26.0:1, 27.0:1, 28.0:1, 29.0:1, 30.0:1, 31.0:1, 32.0:1, 33.0:1, 34.0:1, 35.0:1, 36.0:1, 37.0:1, 38.0:1, 39.0:1, 40.0:1, 41.0:1, 42.0:1, 43.0:1, 33.0:1, 35.0:1, 36.0:1, 37.0:1, 38.0:1, 39.0:1, 40.0:1, 41.0:1, 42.0:1, 43.0:1 44.0:1, 45.0:1, 46.0:1, 47.0:1, 48.0:1, 49.0:1, 50.0:1, 51.0:1, 52.0:1, 53.0:1, 54.0:1, 55.0:1, 56.0:1, 57.0:1, 58.0:1, 59.0:1, 60.0:1, 61.0:1, 62.0:1, 63.0:1, and.
In one embodiment, when L-cystine is present, its mass ratio to osteopontin may be 0.025-200:1, preferably 0.05-25:1, for example 0.025:1, 0.03:1, 0.04:1, 0.05:1, 0.06:1, 0.07:1, 0.08:1, 0.09:1, 0.10:1, 0.15:1, 0.20:1, 0.25:1, 0.30:1, 0.40:1, 0.50:1, 0.60:1, 0.70:1, 0.80:1, 0.90:1, 1.0:1, 1.5:1, 2.0:1, 2.5:1, 3.0:1, 4.0:1, 5.0:1, 6.0:1, 7.0:1, 8.0:1, 9.0:1, 10.0:1, 11.0:1, 12.0:1, 13.0:1, 14.0:1, 15.0:1, 1, 1.0:1, 2.0:1, 5:1, 1.0:1, 5.0:1, 1.0:0:1, 1, 7.0:0:1, 1). 16.0:1, 17.0:1, 18.0:1, 19.0:1, 20.0:1, 21.0:1, 22.0:1, 23.0:1, 24.0:1, 25.0:1, 26.0:1, 27.0:1, 28.0:1, 29.0:1, 30.0:1, 31.0:1, 32.0:1, 33.0:1, 34.0:1, 35.0:1, 36.0:1, 37.0:1, 38.0:1, 39.0:1, 40.0:1, 41.0:1, 42.0:1, 43.0:1, 44.0:1, 45.0:1, 46.0:1, 47.0:1, 48.0:1, 49.0:1, 50.0:1, 36.0:1 16.0:1, 17.0:1, 18.0:1, 19.0:1, 20.0:1, 21.0:1, 22.0:1, 23.0:1, 24.0:1, 25.0:1, 26.0:1, 27.0:1, 28.0:1, 29.0:1, 30.0:1, 31.0:1, 32.0:1, 33.0:1 34.0:1, 35.0:1, 36.0:1, 37.0:1, 38.0:1, 39.0:1, 40.0:1, 41.0:1, 42.0:1, 43.0:1, 44.0:1, 45.0:1, 46.0:1, 47.0:1, 48.0:1, 49.0:1, 50.0:1, and.
In one embodiment, when L-phenylalanine is present, its mass ratio to osteopontin may be 0.005-200:1, preferably 0.025-20:1, for example 0.005:1, 0.010:1, 0.015:1, 0.020:1, 0.025:1, 0.03:1, 0.04:1, 0.05:1, 0.06:1, 0.07:1, 0.08:1, 0.09:1, 0.10:1, 0.15:1, 0.20:1, 0.25:1, 0.30:1, 0.40:1, 0.50:1, 0.60:1, 0.70:1, 0.80:1, 0.90:1, 1.0:1, 1.5:1, 2.0:1, 2.5:1, 3.0:1, 4.0:1, 5.0:1, 6.0:1, 7.0:1, 8.0:1, 9.0:1, 10.0:1, 11.0:1; 12.0:1, 13.0:1, 14.0:1, 15.0:1, 16.0:1, 17.0:1, 18.0:1, 19.0:1, 20.0:1, 21.0:1, 22.0:1, 23.0:1, 24.0:1, 25.0:1, 26.0:1, 27.0:1, 28.0:1, 29.0:1, 30.0:1, 31.0:1, 32.0:1, 33.0:1, 34.0:1, 35.0:1, 36.0:1, 37.0:1, 38.0:1, 39.0:1, 40.0:1, 41.0:1, 42.0:1, 43.0:1, 44.0:1, 45.0:1, 46.0:1, 47.0:1, 33.0:1, 38.0:1, 39.0:1, 40.0:1: 12.0:1, 13.0:1, 14.0:1, 15.0:1, 16.0:1, 17.0:1, 18.0:1, 19.0:1, 20.0:1, 21.0:1, 22.0:1, 23.0:1, 24.0:1, 25.0:1, 26.0:1, 27.0:1, 28.0:1, 29.0:1 30.0:1, 31.0:1, 32.0:1, 33.0:1, 34.0:1, 35.0:1, 36.0:1, 37.0:1, 38.0:1, 39.0:1, 40.0:1, 41.0:1, 42.0:1, 43.0:1, 44.0:1, 45.0:1, 46.0:1, 47.0:1.
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, when pantothenic acid is present, the mass ratio to osteopontin can be from 0.0025 to 25:1, preferably from 0.025 to 2.5:1, for example 0.0025:1, 0.005:1, 0.01:1, 0.015:1, 0.02:1, 0.025:1, 0.03:1, 0.04:1, 0.05:1, 0.06:1, 0.07:1, 0.08:1, 0.09:1, 0.1:1, 0.15:1, 0.20:1, 0.25:1, 0.30:1, 0.40:1, 0.50:1, 0.60:1, 0.70:1, 0.80:1, 0.90:1, 1.0:1, 1.5:1, 2.0:1, 2.5:1, 3.0:1, 3.5:1, 4.0:1, 4.5:1, 5.0:1, 6.0:1, 6.5:1, 7.0:1, 7.5:1, 8.5:1, 8:9:1, 9:1, 0.5:1, 0.0:1, 0.03:1, 0.0:1, 0.04:1, 0.05:1, 0.5:1). 10.0:1, 10.5:1, 11.0:1, 11.5:1, 12.0:1, 12.5:1, 13.0:1, 13.5:1, 14.0:1, 14.5:1, 15.0:1, 15.5:1, 16.0:1, 16.5:1, 17.0:1, 17.5:1, 18.0:1, 18.5:1, 19.0:1, 19.5:1, 20.0:1, 20.5:1, 21.0:1, 21.5:1, 22.0:1, 22.5:1, 23.0:1, 23.5:1, 24.0:1, 24.5:1, 25.0:1, or any range defined by any two thereof, inclusive of any value and subrange within the range.
In one embodiment, when biotin is present, its mass ratio to osteopontin may be 0.0000025-0.025:1, preferably 0.0000125-0.0125:1, for example 0.0000025, 0.000005:1, 0.000010:1, 0.0000125, 0.000015:1, 0.00002:1, 0.00003:1, 0.00004:1, 0.00005:1, 0.00006:1, 0.00007:1, 0.00008:1, 0.00009:1, 0.0001:1, 0.00015:1, 0.0002:1, 0.00025:1, 0.0003:1, 0.0004:1, 0.0005:1, 0.0006:1, 0.0007:1, 0.0008:1, 0.0009:1, 0.001:1, 0.0015:1, 0.002:1, 0.0025:1, 0.003:1, 0.0035:1, 0.0031 0.004:1, 0.0045:1, 0.005:1, 0.006:1, 0.007:1, 0.008:1, 0.009:1, 0.010:1, 0.011:1, 0.012:1, 0.013:1, 0.014:1, 0.015:1, 0.016:1, 0.017:1, 0.018:1, 0.019:1, 0.020:1, 0.021:1, 0.022:1, 0.023:1, 0.024:1, 0.025:1, or any values and subranges encompassed within this range.
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, the mass ratio of the sodium citrate to osteopontin may be from 0.05 to 2000:1, preferably from 0.75 to 100:1, for example, 0.05:1, 0.10:1, 0.15:1, 0.20:1, 0.25:1, 0.30:1, 0.35:1, 0.40:1, 0.45:1, 0.50:1, 0.55:1, 0.60:1, 0.65:1, 0.70:1, 0.75:1, 0.80:1, 0.85:1, 0.90:1, 0.95:1, 1.0:1, 1.5:1, 2.0:1, 2.5:1, 3.0:1, 4.0:1, 5.0:1, 6.0:1, 7.0:1, 8.0:1, 9.0:1, 10.0:1, 11.0:1, 12.0:1, 13.0:1, 14.0:1, 15.0:1, 16.0:1, 17.0:1, 18.0:1, 18.21, 19:1, 2.5:1, 2.0:1, 3.0:1, 4.0:1, 5:1, 6.0:1, 7.0:1, 8.0:1, 9.0:1, 10:1, 10.0:1, 11.0:1, 12.0:1, 13.0:1, 1, 1.0:1, 1.0:1.0.0:1.0:1.0:1, 1.0:1, 1.0:1.0:1:1:1, 0:1:1 10:1 1:1:1 0:1 0:1:1:1 0 0:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1 1 34.0:1, 35.0:1, 36.0:1, 37.0:1, 38.0:1, 39.0:1, 40.0:1, 41.0:1, 42.0:1, 43.0:1, 44.0:1, 45.0:1, 46.0:1, 47.0:1, 48.0:1, 49.0:1, 50.0:1, 51.0:1, 52.0:1, 53.0:1, 54.0:1, 55.0:1, 56.0:1, 57.0:1, 58.0:1, 59.0:1, 60.0:1, 61.0:1, 62.0:1, 63.0:1, 64.0:1, 65.0:1, 66.0:1, 67.0:1, 68.0:1, 69.0:1, 70.0:1, 71.0:1, 72.0:1, 73.0:1, 74:1, 74.0:1, 78:1, 82.1, 82:1, 82.0:1, 82:1, 82.0:1, 60:1, 60.0:1, 61.0:1, 60:1, 62.0:1, 63.0:1, 60:1, 60.0:1, 60.0:0:0 0 0.0:0 0 and 75.0 0 0.0:0 0 0:0 0, and 75.0 0, and 75.0 0 0:0, and 75.0, and, respectively, and, of, and, of, 34.0:1, 35.0:1, 36.0:1, 37.0:1, 38.0:1, 39.0:1, 40.0:1, 41.0:1, 42.0:1, 43.0:1, 44.0:1, 45.0:1, 46.0:1, 47.0:1, 48.0:1, 49.0:1, 50.0:1, 51.0:1, 52.0:1, 53.0:1, 54.0:1, 55.0:1, 56.0:1, 57.0:1, 58.0:1, 59.0:1, 60.0:1: 61.0:1, 62.0:1, 63.0:1, 64.0:1, 65.0:1, 66.0:1, 67.0:1, 68.0:1, 69.0:1, 70.0:1, 71.0:1, 72.0:1, 73.0:1, 74.0:1, 75.0:1, 76.0:1, 77.0:1, 78.0:1, 79.0:1, 80.0:1, 81.0:1, 82.0:1, 83.0:1, 84.0:1, 85.0:1, 86.0:1, or a range defined by any two thereof, and any values and subranges subsumed within the range.
In one embodiment, the mass ratio of potassium chloride to osteopontin, when present, may be 0.05-2000:1, preferably 0.75-100:1, for example, 0.05:1, 0.10:1, 0.15:1, 0.20:1, 0.25:1, 0.30:1, 0.35:1, 0.40:1, 0.45:1, 0.50:1, 0.55:1, 0.60:1, 0.65:1, 0.70:1, 0.75:1, 0.80:1, 0.85:1, 0.90:1, 0.95:1, 1.0:1, 1.5:1, 2.0:1, 2.5:1, 3.0:1, 4.0:1, 5.0:1, 6.0:1, 7.0:1, 8.0:1, 9.0:1, 10.0:1, 11.0:1, 12.0:1, 13.0:1, 14.0:1, 15.0:1, 16.0:1, 17.0:1, 18.0:1, 18.21, 19:1, 2.5:1, 2.0:1, 3.0:1, 4.0:1, 5:1, 6.0:1, 7.0:1, 8.0:1, 9.0:1, 10:1, 10.0:1, 11.0:1, 12.0:1, 13.0:1, 1, 1.0:1, 1.0:1.0.0:1.0:1.0:1, 1.0:1, 1.0:1.0:1:1:1, 0:1:1 10:1 1:1:1 0:1 0:1:1:1 0 0:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1 1 34.0:1, 35.0:1, 36.0:1, 37.0:1, 38.0:1, 39.0:1, 40.0:1, 41.0:1, 42.0:1, 43.0:1, 44.0:1, 45.0:1, 46.0:1, 47.0:1, 48.0:1, 49.0:1, 50.0:1, 51.0:1, 52.0:1, 53.0:1, 54.0:1, 55.0:1, 56.0:1, 57.0:1, 58.0:1, 59.0:1, 60.0:1, 61.0:1, 62.0:1, 63.0:1, 64.0:1, 65.0:1, 66.0:1, 67.0:1, 68.0:1, 69.0:1, 70.0:1, 71.0:1, 72.0:1, 73.0:1, 74:1, 74.0:1, 78:1, 82.1, 82:1, 82.0:1, 82:1, 82.0:1, 60:1, 60.0:1, 61.0:1, 60:1, 62.0:1, 63.0:1, 60:1, 60.0:1, 60.0:0:0 0 0.0:0 0 and 75.0 0 0.0:0 0 0:0 0, and 75.0 0, and 75.0 0 0:0, and 75.0, and, respectively, and, of, and, of, 34.0:1, 35.0:1, 36.0:1, 37.0:1, 38.0:1, 39.0:1, 40.0:1, 41.0:1, 42.0:1, 43.0:1, 44.0:1, 45.0:1, 46.0:1, 47.0:1, 48.0:1, 49.0:1, 50.0:1, 51.0:1, 52.0:1, 53.0:1, 54.0:1, 55.0:1, 56.0:1, 57.0:1, 58.0:1, 59.0:1, 60.0:1: 61.0:1, 62.0:1, 63.0:1, 64.0:1, 65.0:1, 66.0:1, 67.0:1, 68.0:1, 69.0:1, 70.0:1, 71.0:1, 72.0:1, 73.0:1, 74.0:1, 75.0:1, 76.0:1, 77.0:1, 78.0:1, 79.0:1, 80.0:1, 81.0:1, 82.0:1, 83.0:1, 84.0:1, 85.0:1, 86.0:1, or a range defined by any two thereof, and any values and subranges subsumed within the range.
The inventors found that when the above-mentioned optional substances are included in the nutritional composition in addition to 2 '-fucosyllactose (2' -FL) and osteopontin, especially when the quality of the optional substances to osteopontin is within the above-mentioned range, the synergistic effect in promoting neural development such as neuronal maturation, synaptogenesis and myelination, especially in promoting proliferation, maturation and differentiation of OPC into mature OLs and/or myelination 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 present 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-on infant formula) such as an infant formula (e.g. infant formula, follow-on infant 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. For example, the total weight of the food product, relative to the total weight of the food product, the weight content of 2 '-fucosyllactose (2' -FL) may be 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 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%, 3.25%, 2.45%, 2.50%, 2.55%, 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% 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%, and 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%, 3.85%, 2.90%, 3.5%, 3.10%, 3.15%, 3.30%, 3.35% of, 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 and subrange within the range defined by any two thereof and inclusive of the range.
In one embodiment, the nutritional composition is added in an amount such that the osteopontin content by weight relative to the total weight of the food product 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%. For example, the total weight of the food product, relative to the total weight of the food product, the osteopontin may be present in an amount by weight of 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% >. 0.160%, 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%, 0.210%, 0.220%, 0.225%, 0.230%, 0.245%, 0.250%, 0.260%, 0. 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%, 0.310%, 0.315%, 0.320%, 0.325%, 0.335%, 0.350%, 0.360%, 0., 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 values and subranges within the range defined by any two thereof.
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% and the weight content of osteopontin is 0.004-0.4% relative to the total weight of the food product.
When the content of 2' -fucosyllactose and osteopontin in the food is within the above range, the nutrition in each aspect is balanced, and at the same time, the neural development such as neuronal maturation, synaptogenesis and myelination can be remarkably promoted, and particularly, proliferation, maturation and differentiation of OPC into mature OLs and/or myelination characteristics of OL can be promoted.
As mentioned above, the nutritional composition may optionally further comprise 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
-a mineral selected from sodium citrate and/or potassium chloride.
In one embodiment, when yeast beta-glucan is present in the nutritional composition, the nutritional composition may be added in an amount such that the yeast beta-glucan may be present in the food product in an amount of 0.001-2.5% by weight relative to the total weight of the food product, for example 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%, 0.40%, 0.15%, 0.60%, 0.5%, 0.75%, 1.00%, 1.05% and the like 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 any value and subrange encompassed within the range.
In one embodiment, when polydextrose is present in the nutritional composition, the nutritional composition may be added in an amount such that the polydextrose content of the food product may be between 0.02 and 40% by weight relative to the total weight of the food product, for example 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%, 0.45%, 0.50%, 0.55%, 0.60%, 0.65%, 0.70%, 0.85%, 1.30%, 1.40%, 1.50%, 1.80%, 1.00% 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%, 3.70%, 4.40%, 4.70%, 4.80%, 5.00%, 5.10%, 5.20%, 5.30%, 5.40%, 5.60% and the like 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%, and 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%, and, 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, including any value and subrange within the range.
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) weight content in the food product is 0.01-2%, such as 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%, 1.95%, 1.80%, 1.85%, 1.90%, or any range therein, or any two of the ranges thereof, and any range therein, relative to the total weight of the food product.
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 relative to the total weight of the food product may be 0.01-0.8%, such as 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 any value and subrange within this range, as defined by any two thereof.
In one embodiment, when L-phenylalanine is present in the nutritional composition, the nutritional composition may be added in an amount such that the weight content of L-phenylalanine in the food relative to the total weight of the food product is 0.002-0.8%, such as 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 encompassed within the range.
In one embodiment, when pantothenic acid is present in the nutritional composition, the nutritional composition can be added in an amount such that the weight content of pantothenic acid in the food relative to the total weight of the food can be from 0.001% -0.1%, such as 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 amount of biotin in the food relative to the total weight of the food product can be 0.000001% -0.0001%, for example 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 any two thereof and any value and subrange within the range.
In one embodiment, when sodium citrate is present in the nutritional composition, the nutritional composition is added in an amount such that the sodium citrate may be present in the food product in an amount of 0.02-8% by weight relative to the total weight of the food product, for example 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%, and 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%, and 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%, or a range defined by any two thereof, or any value and subrange encompassed within that range.
In one embodiment, when potassium chloride is present in the nutritional composition, the nutritional composition may be added in an amount such that the weight content of potassium chloride in the food may be 0.02-8% relative to the total weight of the food, for example 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%, and 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%, and 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%, or a range defined by any two thereof, or any value and subrange encompassed within that range.
When the above-mentioned optional substances are further contained in the food in the above-mentioned content ranges, the synergistic effect in promoting neural development such as neuronal maturation, synaptogenesis and myelination, in particular, promoting proliferation, maturation and differentiation of OPC into mature OLs and/or OL myelination characteristics is more remarkable.
In addition to the components described above for the nutritional composition, the food product may also comprise other ingredients, such as other proteins, carbohydrates, fats, vitamins, minerals, etc. that are often contained in a formula, such as an infant formula, e.g. milk powder.
In a further aspect, the present invention relates to the use of the above nutritional composition or the above food for non-therapeutic purposes in improving brain development and intelligence in infants, in particular in promoting neurodevelopment (e.g. promoting proliferation, maturation and differentiation of OPC into mature OLs and/or OL).
Examples
Raw materials
In the examples section below, the raw materials used are as follows, unless otherwise indicated.
2 '-fucosyllactose (2' -FL): glyCare TM 2FL 9000,2' -fucosyllactose content 96.0 wt%
Osteopontin: danish Arla Foods Ingredients Group P/S osteopontin powder Lacprodan OPN-10, osteopontin content 95.6 wt%
In the following sections, unless otherwise specified, in referring to parts by mass of components in the nutritional composition and ratios, the parts by mass refer to parts by mass of 2 '-fucosyllactose (2' -FL) and osteopontin as active ingredients, and the ratios refer to the mass ratio between 2 '-fucosyllactose (2' -FL) and osteopontin as active ingredients.
A variety of nutritional compositions were formulated 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
| Numbering device | 2' -FL (parts by mass) | OPN (quality) |
| Example 1 | 10 | 1 |
| Example 2 | 0.1 | 1 |
| Example 3 | 100 | 1 |
| Example 4 | 1000 | 1 |
| Comparative example 1 | 0 | 1 |
| Comparative example 2 | 1 | 0 |
Experimental examples of cells
At present, the research on brain development is limited to the research on passive memory by utilizing animal experiments, the development of neuron cells is not discussed, and the influence of specific doses of the composition on the early brain development is not explored. The present invention uses an in vitro model of primary cell culture containing neurons and OPCs to assess the effects of nutritional mixtures on myelination and neurons. The influence of components containing 2' -FL and OPN in different proportions on the development of brain nerve cells is experimentally researched, and the method systematically and intuitively evaluates the influence on early brain development and has profound significance on guiding the application of the two components.
1 materials and methods
1.1 instruments and reagent consumables
A cell incubator; a confocal laser fluorescence microscope; a centrifuge; an electronic balance; vortex appearance, water-bath, tissue homogenizer.
Neural cell culture medium; antibodies such as A2B5, MAG and MBP.
1.2 Experimental methods
1.2.1 neural primary cell acquisition
All experiments were ethically approved and primary mixed cultures of neurons and OLs were performed as follows. Briefly, forebrains of neonatal mice were dissociated with Trypsin (Trypsin EDTA 1X, PAN BIOTECH) for 20 min at 37 ℃. The reaction was stopped after adding Dulbecco's modified Eagle's Medium (DMEM, PAN BIOTECH) containing DNAase grade I II (0.1 mg/ml, PAN BIOTECH) and 10% fetal calf serum (FCS, GIBCO). The cells were mechanically separated three times by a 10ml pipette and then centrifuged at 515g for 10 minutes 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 (L Glu, 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 incubator at 37℃under air (95%) -CO2 (5%).
1.2.2 neural cell culture
The same number of cells were placed on 48 well plates and then incubated between 12, 18 or 30DIV, half of the medium was changed every other day, and the mixture or individual nutrients (nutritional composition comprising 2' -FL and/or OPN prepared above) were added to fresh medium.
1.2.3 immunohistochemical experiments
12. After 18 and 30DIV, cells were fixed with a cold mixture of 95% ethanol and acetic acid (5%) for 5 minutes. The non-specific sites were then blocked with Phosphate Buffered Saline (PBS) containing 0.1% saponin (Sigma) and 1% FCS (GIBCO) for 15 min at room temperature.
At 12DIV, the neural cells were incubated with the mouse monoclonal antibody A2B5 (dilution: 1/200, millipore, MAB312 RX) for 2h at room temperature, followed by 2h at room temperature with the neurofilament antibody (dilution: 1/500, sigma, N4142). Finally, a secondary anti-goat anti-rabbit antibody (diluted 1/400, SIGMA, SAB 4600084) was used for co-incubation for 1h at room temperature.
At 18DIV, the neural cells were incubated with the mouse monoclonal antibody MAG (dilution: 1/400, millipore, MAB 1567) and the neuromicrofilament antibody (dilution: 1/500, sigma, N4142) for 2h. Then incubated with a secondary anti-goat anti-rabbit antibody (dilution: 1/400, sigma, SAB 4600042) and a secondary anti-goat anti-rabbit antibody (dilution: 1/400, SIGMA, SAB 4600084) for 1h at room temperature.
At 30DIV, the 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 incubated with a secondary goat anti-mouse antibody (dilution: 1/800, sigma, SAB 4600042) and a secondary goat anti-rabbit (dilution: 1/400, SIGMA, SAB 4600084) for 1h at room temperature.
1.2.4 microscope photographs
20-fold magnification was performed using ImageXpress and equipped with LED lights (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 A2B5 expressing cells under 12DIV conditions, and the results were expressed as the average number of A2B5 expressing cells per well per figure.
Differentiation of OPCs to OLs was assessed by counting the number of MAG positive cells in cell culture at 18 DIV. Results are expressed as average cell number per picture and per well. The morphological maturity of MAG-positive cells was assessed by measuring the average surface area (μm/graph/well) of MAG-positive cells in 18DIV wells.
The maturity of OLs was estimated by counting the number of MBP-positive cells (average number of cells per well per picture) and the average surface area of MBP-positive cells at 30DIV (μm per picture per well).
1.3 cell experiment grouping
Cell inoculation was performed on 96-well plates for a certain period of time, half of the medium was replaced every other day, and different concentrations of the mixture or 2 FL-alone mixture (12, 18, 30d added respectively) was added to fresh primary cell-specific medium, 6 replicates each. The blank, positive and sample intervention groups were compared with an Olesoxim (300 nM, demonstrated accelerated OLs maturation and myelination in vitro and in vivo) as positive control, respectively. Immunohistochemistry (MBP, NF, A2B 5) measures the effect of OPN and 2FL alone or in combination on OPCs population, OL maturation and differentiation, myelin formation, and neurite outgrowth. The specific experimental dosages are shown in Table 2 below.
TABLE 2 cell experiment dose
1.4 statistical analysis
Results are expressed as mean ± standard error (mean ± SEM), and are determined to have significant differences when p <0.05 using SPSS software for T-test and one-way ANOVA.
2 experimental results
2.1 Effect of samples on nerve cells
To measure the effect of mixed nutrition or individual nutrition treatments on OPCs, we assessed the number of positive cells labeled A2B5 after 12DIV to estimate the number of OPCs.
The average A2B5 positive cell numbers measured per picture and per well are shown in table 3.
Table 3 effects of different nutritional composition samples comprising 2' -FL and/or OPN on the number of A2B5 positive cells.
Sample treatment results showed that the 2' -FL high dose, OPN high dose group significantly increased the number of A2B5 positive cells compared to the blank group, indicating that both components contributed to proliferation of oligodendrocyte-like precursor cells.
In addition, the dosages of 2' -FL and OPN used in cell experimental example 9 (corresponding example 1) were the same as those of cell experimental examples 3 and 4 (corresponding examples 1 and 2), respectively. As can be seen from the above table, cell experiment example 3 and cell experiment example 4 increased the number of A2B5 positive cells by 23.334 and 19.834, respectively, relative to cell experiment example 1 (corresponding to the blank control group), while cell 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), indicating that there was a synergistic effect between 2' -FL and OPN, which could synergistically increase the number of A2B5 positive cells.
2.2 Effect of samples on OPC cell maturation
To measure the effect of mixed or individual nutritional treatments on OPCs cell maturation, we assessed the number of positive cells for MBP-labeled after 30 DIV.
The average MBP positive cell numbers measured per picture and per well are shown in table 4.
Table 4. Effects of different nutritional composition samples comprising 2' -FL and/or OPN on the number of MBP positive cells.
As can be seen from table 4, the positive control, olesoxim, showed an increase in the number of MBP positive cells compared to the blank control; the 2' -FL high dose, OPN high dose group significantly increased the number of MBP positive cells, suggesting that both components contribute to oligodendrocyte precursor cell maturation.
In addition, as can be seen from the above table, cell experiment example 3 and cell experiment 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 cell experiment example 1 (corresponding to the blank control group), while cell experiment example 9 (corresponding to example 1) increased the number of MBP-positive cells by 84.167, which is greater than the sum of the former two (34.667+28.834= 63.501), indicating that there was a synergistic effect between 2' -FL and OPN, capable of synergistically increasing the number of MBP-positive cells.
The invention provides research on the composition of Osteopontin (OPN) and 2 '-fucosyllactose (2' -FL) in the aspect of brain development, and provides a new idea for developing future functional foods. Osteopontin and 2 '-fucosyllactose (2' -FL) are able to promote proliferation, maturation and differentiation of OPC into mature OLs and/or myelination properties of OL at early brain development stages. Has wide prospect in the aspects of neuron development and brain development.
Application examples
In the following application examples, "parts" are parts by weight, and% contents of components are% by weight.
In addition, in the following application examples, the following sources of raw materials are used unless otherwise indicated.
Whole milk powder: heilongjiang Feihe milk Co.Ltd
Concentrated whey protein powder rich in osteopontin (osteopontin 5.2%): denmark Arla Foods Ingredients Group P/S
2 '-fucosyllactose (2' -fucosyllactose 96.0%): glyCare TM 2FL 9000
Desalted whey powder: french Euros (Red bird)
Galacto-oligosaccharides: bowling-bowl biological stock Co.Ltd
Mixing vegetable oil: jiaji grain oil (Nantong) Co., ltd
And (3) compounding vitamins: dissmann vitamins (Shanghai) Co., ltd
Compounding minerals: dissmann vitamins (Shanghai) Co., ltd
Whole milk powder: heilongjiang Feihe milk Co.Ltd
Osteopontin powder (osteopontin 95.6%): danish Arla Foods Ingredients Group P/S, lacprodan OPN-10
Solid corn syrup, bowling organism stock Co.Ltd
Fructo-oligosaccharides: bowling-bowl biological stock Co.Ltd
Skimmed milk powder: ireland Kerry
Isomaltooligosaccharides: bowling-bowl biological stock Co.Ltd
Raw milk: heilongjiang Feihe milk Co.Ltd
Mono-di-glycerol fatty acid ester: danish Ke (China Co., ltd.)
Application example 1
An 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 comprises the following raw materials: 195 parts of whole milk powder, 38.5 parts of osteopontin-enriched concentrated whey protein powder (5.2% of osteopontin in each part), 20.8 parts of 2 '-fucosyllactose (96.0% of 2' -fucosyllactose in each part), 350 parts of desalted whey powder, 117 parts of lactose, 83.7 parts of galactooligosaccharide, 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 vitamins and 2 parts of compound minerals; and uniformly mixing the raw materials, pasteurizing, homogenizing, evaporating, concentrating and spray drying to obtain a powdery semi-finished product, and filling nitrogen into the uniformly mixed milk powder and packaging to obtain the final product. The product contains 2% of 2' -fucosyllactose and 0.2% of osteopontin.
Application example 2
An 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 comprises the following raw materials: 183 parts of whole milk powder, 7.7 parts of osteopontin-enriched 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), 350 parts of desalted whey powder, 175 parts of lactose, 85.1 parts of galactooligosaccharide, 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 vitamins and 2 parts of compound minerals; and uniformly mixing the raw materials, pasteurizing, homogenizing, evaporating, concentrating and spray drying to obtain a powdery semi-finished product, and filling nitrogen into the uniformly mixed milk powder and packaging to obtain the final product. 0.4% of 2' -fucosyllactose and 0.04% of osteopontin in the product.
Application example 3
The infant formula containing 2' -fucosyllactose and osteopontin is prepared from the following components in parts by weight per 1000 parts of infant formula:
the milk powder of the invention comprises 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-enriched 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 galactooligosaccharide, 75 parts of mixed vegetable oil, 5 parts of calcium citrate, 3 parts of compound vitamin and 1 part of compound mineral; and uniformly mixing the raw materials, pasteurizing, homogenizing, evaporating, concentrating and spray drying to obtain a powdery semi-finished product, and filling nitrogen into the uniformly mixed milk powder and packaging to obtain the final product. The content of 2' -fucosyllactose in the product is 1%, and the osteopontin is 0.1%.
Application example 4
The infant formula containing 2' -fucosyllactose and osteopontin is prepared from the following components in parts by weight per 1000 parts of infant formula:
the milk powder of the invention comprises the following raw materials: 433 parts of whole milk powder, 3.85 parts of osteopontin-enriched concentrated whey protein powder (5.2% of osteopontin in each part), 2.08 parts of 2 '-fucosyllactose (96.0% of 2' -fucosyllactose in each part), 350 parts of desalted whey powder, 48 parts of lactose, 79.07 parts of galactooligosaccharide, 75 parts of mixed vegetable oil, 5 parts of calcium citrate, 3 parts of compound vitamin and 1 part of compound mineral; and uniformly mixing the raw materials, pasteurizing, homogenizing, evaporating, concentrating and spray drying to obtain a powdery semi-finished product, and filling nitrogen into the uniformly mixed milk powder and packaging to obtain the final product. The content of 2' -fucosyllactose in the product is 0.2%, and the osteopontin is 0.02%.
Application example 5
The prepared milk powder containing 2' -fucosyllactose and osteopontin is suitable for middle-aged and elderly people, and each 1000 parts of prepared milk powder is prepared from the following components in parts by weight:
the milk powder of the invention comprises the following raw materials: 750 parts of whole milk powder, 4.18 parts of osteopontin powder (95.6% of osteopontin in each part), 195 parts of solid corn syrup, 46.4 parts of fructo-oligosaccharides, 0.42 part of 2 '-fucosyllactose (96.0% of 2' -fucosyllactose in each part), 3 parts of compound vitamin and 1 part of compound mineral; and uniformly mixing the raw materials, pasteurizing, homogenizing, evaporating, concentrating and spray drying to obtain a powdery semi-finished product, and filling nitrogen into the uniformly mixed milk powder and packaging to obtain the final product. 0.04% of 2' -fucosyllactose and 0.4% of osteopontin in the product.
Application example 6
The prepared milk powder containing 2' -fucosyllactose and osteopontin is suitable for pregnant women, and each 1000 parts of prepared milk powder is prepared from the following components in parts by weight:
the milk powder of the invention comprises the following raw materials: 336 parts of whole milk powder, 0.78 part of osteopontin powder (5.2% of osteopontin in each part), 0.42 part of 2 '-fucosyllactose (96.0% 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; and uniformly mixing the raw materials, pasteurizing, homogenizing, evaporating, concentrating and spray drying to obtain a powdery semi-finished product, and filling nitrogen into the uniformly mixed milk powder and packaging to obtain the final product. The 2' -fucosyllactose content in the product is 0.04%, and the 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:
according to the invention, 944.35 parts of raw cow 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 are mixed; mixing the above materials, homogenizing, UHT sterilizing, homogenizing, and aseptically packaging to obtain the final product. The 2' -fucosyllactose content in the product is 4%, and the osteopontin content is 0.4%.
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:
according to the invention, 941.49 parts of raw cow 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 parts of mono-diglyceride fatty acid ester are mixed; mixing the above materials, homogenizing, UHT sterilizing, homogenizing, and aseptically packaging to obtain the final product. The 2' -fucosyllactose content in the product is 4%, and the osteopontin is 0.004%.
Based on what is described in the priority application, the inventors have made further experiments as follows.
The protocol for the combination of 2' -FL and OPN was not repeated in the following sections. The inventors directly refer to the results of the experiments described in the priority text in performing data analysis.
The following experimental part and the experimental part recorded in the priority application are two independent parts, and the experimental group and the result display chart are respectively and independently encoded.
The present invention uses an in vitro model of primary cell culture containing neurons and OL to assess the effect on myelination by breast milk oligosaccharide compositions. A mixotrophic substance is added to the mixed cell culture to promote proliferation, maturation and differentiation of OPC into mature OL and/or myelination properties of OL. The density of OPC after 12d in vitro culture was first assessed. OPC differentiation to OL and the level of 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 sections, unless otherwise specified, in referring to parts by mass of components in the nutritional composition and ratios, the parts by mass refer to parts by mass of 2 '-fucosyllactose (2' -FL), osteopontin (OPN) and yeast β -glucan as active ingredients, and the ratios refer to mass ratios between 2 '-fucosyllactose (2' -FL), osteopontin (OPN) and yeast β -glucan as active ingredients.
A2B5 is a marker of oligodendrocytes.
MAG is a sialic acid binding immunoglobulin-like lectin, which is expressed predominantly in periaxon regions of myelin, although it represents only a small fraction of the total protein content of myelin. It appears to play an important role in oligodendrocyte-axon interactions and mediate bi-directional signaling between axons and OLs to support myelination.
MBP is strongly expressed in mature myelinated OL, 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 cohesive reticulin network, which is associated with OL maturation.
In the examples of the present invention, 2' -fucosyllactose was expressed as GlyCare TM 2FL 9000 (2' -FL content 96.0%) was added.
In the examples of the present invention, osteopontin was added as Danish Arla Foods Ingredients Group P/S, lacprodan OPN-10 (OPN content 95.6%).
In the examples of the present invention, yeast beta-glucan was added in the form of HH1006 from Shanghai garden food technologies Co., ltd.
At present, the research on brain development is limited to the research on passive memory by utilizing animal experiments, the development of neuron cells is not discussed, and the influence of specific doses of the composition on the early brain development is not explored. The present invention uses an in vitro model of primary cell culture containing neurons and OPC to evaluate the effect of a nutritional mixture on myelination and neurons. The influence of components containing 2' -FL, osteopontin and yeast beta-glucan in different proportions on the development of brain nerve cells is experimentally researched, and the method systematically and intuitively evaluates the influence on early brain development and has profound significance on the application of a guiding composition.
1 materials and methods
1.1 instruments and reagent consumables
Cell incubator, laser confocal fluorescence microscope, centrifuge, electronic balance, vortex appearance, water bath, tissue homogenizer.
Neural cell culture medium, antibodies such as A2B5, MAG, MBP, and the like.
1.2 Experimental methods
1.2.1 neural primary cell acquisition
All experiments were ethically approved and neuronal and OL primary mixed cultures were performed as follows. Briefly, forebrains of neonatal mice were dissociated with Trypsin (Trypsin EDTA 1X, PAN BIOTECH) for 20 min at 37 ℃. Trypsin was then stopped by adding cell culture medium DMEM (PAN BIOTECH) containing DNase (0.1 mg/ml, PAN BIOTECH) and 10% fetal bovine serum (GIBCO). The cells were mechanically separated three times by a 10ml pipette and then centrifuged at 515g for 10 minutes 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 (L Glu, PAN BIOTECH), 2% P/S solution (PAN BIOTECH), 1% FCS and 10ng/ml platelet derived growth factor (PDGF-AA, PAN BIOTECH). The 48-well plate is stored in a humidified incubator at 37 ℃ and the environment is air (95%) -CO 2 (5％)。
1.2.2 neural cell culture
Starting cell numbers were the same, in 48 well plates, in vitro experiments were incubated for 12, 18 or 30d, half of the medium was changed every other day, and the nutritional composition comprising 2' -FL, OPN and/or yeast beta-glucan prepared in the examples of the present invention was added to fresh medium.
1.2.3 immunohistochemical experiments
12. After 18 and 30d in vitro cultures, cells were fixed with a cold mixture of 95% ethanol and acetic acid (5%) for 5 minutes. The non-specific sites were then blocked with Phosphate Buffered Saline (PBS) containing 0.1% saponin (Sigma) and 1% FCS (GIBCO) for 15 min at room temperature.
At 12d in vitro culture, the neural cells were incubated with the mouse monoclonal antibody A2B5 (dilution: 1/200, millipore, MAB312 RX) for 2h at room temperature, followed by 2h at room temperature with the neurofilament antibody (dilution: 1/500, sigma, N4142). Finally, a secondary anti-goat anti-rabbit antibody (diluted 1/400, SIGMA, SAB 4600084) was used for co-incubation for 1h at room temperature.
At 18d in vitro culture, the neural cells were incubated with the mouse monoclonal antibody MAG (dilution: 1/400, millipore, MAB 1567) and the neuromicrofilament antibody (dilution: 1/500, sigma, N4142) for 2h. Then incubated with a secondary anti-goat anti-rabbit antibody (dilution: 1/400, sigma, SAB 4600042) and a secondary anti-goat anti-rabbit antibody (dilution: 1/400, SIGMA, SAB 4600084) for 1h at room temperature.
At 30d in vitro culture, the 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 incubated with a secondary goat anti-mouse antibody (dilution: 1/800, sigma, SAB 4600042) and a secondary goat anti-rabbit (dilution: 1/400, SIGMA, SAB 4600084) for 1h at room temperature.
1.2.4 microscope photographs
20-fold magnification was performed using ImageXpress and equipped with LED lights (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 A2B5 expressing cells under in vitro culture conditions for 12d, and the results were expressed as the average number of A2B5 expressing cells per well per figure.
Differentiation of OPCs to 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 maturity of OLs was estimated by counting the number of MBP positive cells (average number of cells per well per picture).
1.3 cell experiment grouping
The prepared cells were inoculated on a 48-well plate and cultured for a certain period of time, half of the culture medium was replaced every other day, and experimental reagents (12, 18, 30d were added respectively) at different concentrations were added to the fresh primary cell culture medium, 6 replicates per sample. The blank, positive and experimental groups (comparative and example) were compared with Olesoxim (300 nM) as a positive control, which was demonstrated to accelerate OLs maturation and myelination in vitro and in vivo, respectively. Immunohistochemistry was performed to determine the effect of OPN and 2FL, yeast beta-glucan, alone or in combination, on OPC population, OL maturation and differentiation, myelin formation, and neurite outgrowth. The specific experimental dosages are shown in Table 1 below (concentrations are final concentrations).
Table 1: cell experiment dose
1.4 statistical analysis
Results are expressed as mean ± standard error (mean ± SEM), and the T-test and one-way ANOVA test is performed using SPSS software, and a significant difference is determined when p < 0.05.
2 experimental results
To measure the effect of the addition of reagent on OPC, the number of positive cells labeled A2B5 after 12d in vitro culture was evaluated to estimate the number of OPC. The average A2B5 positive cell numbers measured per well are shown in table 2.
Table 2: effect of added reagents on the number of A2B 5-positive cells
Sample treatment results showed that both 2' -FL and OPN significantly increased the number of A2B5 positive cells compared to the blank, as if both components contributed to proliferation of oligodendrocyte-like precursor cells. After being mixed with 2-FL and OPN, the yeast beta-glucan can obviously increase the number of the A2B5 positive cells.
Effect of additive reagents on OPC cell myelination
To measure the effect of the addition of the reagent on the myelination of OPC cells, the number of positive cells labeled MAG after 18d in vitro culture was assessed. The average MAG positive cell numbers measured per well are shown in Table 3.
Table 3: effect of additive agents on MAG-positive cell number
Both 2' -FL and OPN significantly increased the number of MAG positive cells compared to the placebo group, as it appears that both components contribute to myelination of oligodendrocyte precursor cells. After mixing with 2-FL and OPN, yeast beta-glucan can significantly increase the number of MAG positive cells, indicating that the combination has a synergistic effect.
Effect of added reagents on OPC cell maturation
To measure the effect of the addition of the reagent on OPCs cell maturation, the number of positive cells for labeled MBP after 30d in vitro culture was assessed. The average MBP positive cell numbers measured per well are shown in table 4.
Table 4: effect of added reagents on MBP-positive cell number
Both 2-FL and OPN significantly increased MBP positive cell numbers, suggesting that both components contribute to maturation of oligodendrocyte-like precursor cells. After being mixed with 2-FL and OPN, the yeast beta-glucan can obviously increase the number of MBP positive cells, which proves that the combination has a synergistic effect
The above-described embodiments are merely preferred embodiments for fully explaining the present invention, and the scope of the present invention is not limited thereto. Equivalent substitutions and modifications will occur to those skilled in the art based on the present invention, and are intended to be within the scope of the present invention. The protection scope of the invention is subject to the claims.
Claims (18)
1. A neurodevelopmental nutritional composition comprising yeast beta-glucan, characterized in that the composition comprises 2' -fucosyllactose and osteopontin and yeast beta-glucan.
2. Composition according to claim 1, characterized in that the mass ratio of 2' -fucosyllactose to osteopontin in the composition is 0.05-2000:1, preferably 0.1-1000:1, further preferably 1-100:1, still further preferably 5-50:1, most preferably 10-20:1.
3. Composition according to claim 2, characterized in that the mass fraction of yeast β -glucan in the composition is not less than 0.001%, preferably not less than 0.1%, more preferably not less than 1%, even more preferably not less than 2.5%.
4. A composition according to claim 3, characterized in that the content ratio of 2' -fucosyllactose, yeast β -glucan and osteopontin in the composition is 0.01-2000:0.015-150:1, preferably 0.01-1000:0.15-150:1, further preferably 0.1-100:1.5-150:1.
5. A method for preparing the composition according to any one of claims 1-4, characterized in that the 2' -fucosyllactose, osteopontin and yeast beta-glucan 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 according to claim 6, wherein the food product is an infant food product.
8. The use according to claim 6, wherein the infant food is infant formula.
9. The use according to claim 6, wherein the food is a maternal food.
10. An edible product comprising a composition according to any one of claims 1 to 4.
11. The edible product of claim 10, wherein the edible product is an infant edible product.
12. The edible product of claim 10, wherein the infant food product is infant formula.
13. The edible product according to claim 10, wherein the edible product is a maternal edible product.
14. The edible product according to any one of claims 10 to 13, wherein the weight content of 2' -fucosyllactose in the edible product is 0.04 to 4%.
15. The food product of claim 14, wherein the osteopontin is present in the food product in an amount of 0.004-0.4% by weight.
16. The food product of claim 14, wherein the yeast beta-glucan is present in the food product in an amount of 0.01 to 0.05%.
17. Use of a composition according to any one of claims 1-4 for the preparation of a medicament for promoting the development of cognitive function.
18. Use of a composition according to any one of claims 1 to 4 or an edible product according to any one of claims 10 to 15 for non-therapeutic purposes in promoting the development of cognitive functions.
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Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20150305385A1 (en) * | 2014-04-25 | 2015-10-29 | Mead Johnson Nutrition Company | Pediatric nutritional composition with human milk oligosaccahrides, prebiotics and probiotics |
| CN106998775A (en) * | 2014-11-26 | 2017-08-01 | 雅培制药有限公司 | Infant formula with RRR alpha tocopherols, 2 ' fucosyllactoses and probiotics |
| CN109043542A (en) * | 2018-09-11 | 2018-12-21 | 内蒙古伊利实业集团股份有限公司 | The application of human milk oligosaccharides and/or its precursor in the composition of preparation prevention children caries disease |
| CN112040973A (en) * | 2018-04-25 | 2020-12-04 | 健合香港有限公司 | Combination of osteopontin and 2' -fucosyllactose for use as a medicament |
| CN112535218A (en) * | 2020-12-08 | 2021-03-23 | 石家庄君乐宝乳业有限公司 | Maternal emulsified infant formula milk powder for promoting intelligence development and intestinal health and preparation method and application thereof |
| 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 |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US10328091B2 (en) * | 2014-10-31 | 2019-06-25 | Nestec S.A. | Composition comprising Fut2-dependent oligosaccharides and Lacto-N-neotetraose for use in promoting brain development and cognition |
| 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 |
| CN110973263A (en) * | 2019-12-19 | 2020-04-10 | 河北三元食品有限公司 | Infant nutrition composition containing human milk oligosaccharide |
| CN112841316B (en) * | 2021-02-03 | 2021-11-05 | 合生元（广州）健康产品有限公司 | Personalized nutritional composition comprising oligosaccharides |
| CN112890200B (en) * | 2021-03-08 | 2021-11-12 | 合生元（广州）健康产品有限公司 | Nutritional composition for promoting growth pursuit of low-weight infants |
| CN112914104B (en) * | 2021-03-08 | 2021-11-12 | 合生元（广州）健康产品有限公司 | Nutritional composition for preventing obesity in infants |
-
2022
- 2022-05-12 CN CN202210520202.3A patent/CN115399480A/en active Pending
- 2022-08-31 CN CN202211060565.XA patent/CN115413789A/en active Pending
- 2022-09-07 CN CN202211090064.6A patent/CN116268412A/en active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20150305385A1 (en) * | 2014-04-25 | 2015-10-29 | Mead Johnson Nutrition Company | Pediatric nutritional composition with human milk oligosaccahrides, prebiotics and probiotics |
| CN106998775A (en) * | 2014-11-26 | 2017-08-01 | 雅培制药有限公司 | Infant formula with RRR alpha tocopherols, 2 ' fucosyllactoses and probiotics |
| CN112040973A (en) * | 2018-04-25 | 2020-12-04 | 健合香港有限公司 | Combination of osteopontin and 2' -fucosyllactose for use as a medicament |
| CN109043542A (en) * | 2018-09-11 | 2018-12-21 | 内蒙古伊利实业集团股份有限公司 | The application of human milk oligosaccharides and/or its precursor in the composition of preparation prevention children caries disease |
| CN112535218A (en) * | 2020-12-08 | 2021-03-23 | 石家庄君乐宝乳业有限公司 | Maternal emulsified infant formula milk powder for promoting intelligence development and intestinal health and preparation method and application thereof |
| 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 |
Non-Patent Citations (1)
| Title |
|---|
| RULAN JIANG 等: "Effects of Milk Osteopontin on Intestine，Neurodevelopment，and Immunity", NESTLE NUTRITION INSTITUTE WORKSHOP SERIES, vol. 94, 31 March 2020 (2020-03-31), pages 3 - 4 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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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