WO2023241110A1 - 营养组合物、包含其的食品以及该营养组合物的用途 - Google Patents

营养组合物、包含其的食品以及该营养组合物的用途 Download PDF

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WO2023241110A1
WO2023241110A1 PCT/CN2023/079303 CN2023079303W WO2023241110A1 WO 2023241110 A1 WO2023241110 A1 WO 2023241110A1 CN 2023079303 W CN2023079303 W CN 2023079303W WO 2023241110 A1 WO2023241110 A1 WO 2023241110A1
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Prior art keywords
bone
food
fucosyllactose
nutritional composition
lactose
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PCT/CN2023/079303
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English (en)
French (fr)
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崔东影
解庆刚
陆思宇
蒋士龙
张永久
蔡方良
冷友斌
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黑龙江飞鹤乳业有限公司
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Publication of WO2023241110A1 publication Critical patent/WO2023241110A1/zh

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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
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/115—Fatty acids or derivatives thereof; Fats or oils
    • A23L33/12—Fatty acids or derivatives thereof
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs

Definitions

  • the present invention relates generally to the field of food. Specifically, the present invention relates to a nutritional composition for promoting bone development, a food product comprising the nutritional composition, and the use of the nutritional composition or food product. More specifically, the present invention relates to a milk oligosaccharide (for example selected from 2'-fucosyllactose (2'-FL), 3'-fucosyllactose (3'-FL), lactose- Neutral fucosylation of N-fucopentose I (LNFP I), lactose-N-difucohexaose I (LNDFH I), lactose-N-difucohexaose II (LNDFH II)
  • HMO human milk oligosaccharides
  • ARA arachidonic acid
  • Bone is a highly active connective tissue. It can repair its own micro-damage through bone metabolism and bone remodeling, and maintain the homeostasis balance of bone structure, load and calcium content. At the same time, bone also serves as an endocrine organ to regulate metabolic processes and is essential for maintaining the human body. Vital organs of life. Starting from the newborn period, bone mass increases with age until bone development reaches its peak in adolescence. Research has found that by paying attention to increasing bone mass during adolescence, individual peak bone mass can be achieved in youth. Therefore, bone growth and development during adolescence is crucial to bone maturation. Studies have pointed out that bone mineral density (BMD) in adolescence determines peak bone mass and subsequent bone loss rate in adulthood.
  • BMD bone mineral density
  • Reduced BMD can lead to insufficient bone mass, which can lead to a series of bone diseases such as rickets and rickets, seriously affecting the bone health of adolescents.
  • nutritional supplementation is an important factor affecting peak bone mass. Intake of nutrients can increase peak bone mass and promote bone formation. Therefore, seeking a natural functional nutrient to increase BMD and bone formation in adolescents is of great significance for increasing bone mass, preventing bone diseases such as fractures in adolescents and osteoporosis in middle-aged and elderly people, and maintaining bone health.
  • Bone contains an extracellular protein matrix (osteoid) in which bone cells are interspersed and a mineral component consisting of calcium salts and other minerals is located within the extracellular matrix. Bone undergoes remodeling by a resorption process, in which bone is degraded by osteoclasts and then replaced (reformed) by osteoblasts. Remodeling occurs to regulate calcium homeostasis, repair bone damaged by daily stress, and occurs when growth or mechanical stress patterns change. Bone shaping. Osteoclasts degrade bone in a specific area and then undergo apoptosis. Osteoblasts rebuild new bone and mediate its remineralization. During remineralization, some osteoblasts become encased in calcified material and then become osteocytes.
  • osteoid extracellular protein matrix
  • An object of the present invention is to provide a nutritional composition that can promote bone development, especially the bone development of infants and children.
  • Another object of the present invention is to provide a food containing the nutritional composition.
  • Another object of the present invention is to provide said nutritional composition or food in promoting bone development (for example, in humans or animals) (for example, improving at least one of the following: bone density, absorption of calcium and/or phosphorus in the blood, bone density, etc.). Beam relative volume, trabecular bone thickness, trabecular bone separation, serum alkaline phosphatase ALP content and other indicators related to bone development), especially for non-therapeutic purposes in promoting bone development in infants and children.
  • the inventors of the present invention have found that by combining human milk oligosaccharides (for example, selected from 2'-fucosyllactose (2'-FL), 3'-fucosyllactose (3'-FL), lactose-N- Breast milk has low neutral fucosylation of fucopentose I (LNFP I), lactose-N-difucohexaose I (LNDFH I), and lactose-N-difucohexaose II (LNDFH II).
  • human milk oligosaccharides for example, selected from 2'-fucosyllactose (2'-FL), 3'-fucosyllactose (3'-FL)
  • lactose-N- Breast milk has low neutral fucosylation of fucopentose I (LNFP I), lactose-N-difucohexaose I (LNDFH I), and lactose-N-dif
  • HMOs Polysaccharides
  • 2'-fucosyllactose (2'-FL) 2'-fucosyllactose
  • ARA arachidonic acid
  • HMOs may synergistically promote bone development and health (e.g., in terms of bone density, blood calcium, and /or synergistically improve at least one of the indicators related to bone development and health such as phosphorus absorption, relative volume of trabecular bone, thickness of trabecular bone, separation of trabecular bone, alkaline phosphatase ALP, etc.).
  • the present invention is implemented as follows:
  • a nutritional composition which includes or consists of:
  • human milk oligosaccharides preferably neutral fucosylated human milk oligosaccharides, which are preferably selected from the group consisting of 2'-fucosyllactose, 3'-fucosyllactose, lactose-N-fucopentan One or more of sugar I, lactose-N-difucohexaose I, lactose-N-difucohexaose II, preferably 2'-fucosyllactose; and
  • the amount of breast milk oligosaccharide is 0.01-10000, preferably 0.05-5000, preferably 0.1-3000, preferably 0.3-1000, preferably 2-500, preferably 3-200 parts by mass relative to 1 part by mass of arachidonic acid.
  • Food comprising the nutritional composition according to any one of items 1-3.
  • infant formula food such as infant formula food
  • follow-up formula food toddler formula food
  • infant formula milk powder such as infant formula milk powder, toddler formula milk powder
  • Infant food supplements nutritional or dietary supplements
  • milk powder for pregnant women infant formula food, follow-up formula food
  • infant formula milk powder such as infant formula milk powder, toddler formula milk powder
  • infant food supplements such as infant food supplements
  • nutritional or dietary supplements or milk powder for pregnant women.
  • the mass content of breast milk oligosaccharides is at least 0.005%, preferably at least 0.01%, preferably at least 0.05%, and preferably at most 20.0%, preferably at most 10.0%, and
  • the mass content of arachidonic acid is at least 0.0005%, preferably at least 0.001%, preferably at least 0.003%, and preferably at most 1.0%, preferably at most 0.5%.
  • the mass content of breast milk oligosaccharides is at least 0.05%, preferably at least 0.06%, and preferably at most 10%, preferably at most 6%, preferably at most 3%, and
  • the mass content of arachidonic acid is at least 0.0025%, preferably at least 0.0030%, and preferably at most 1%, preferably at most 0.6%, preferably at most 0.3%;
  • the mass ratio of breast milk oligosaccharides and arachidonic acid is 2-300:1, preferably 3-200:1.
  • promoting bone development includes improving at least one of the following: bone density, absorption of calcium and/or phosphorus in the blood, relative volume of trabecular bone, relative number of trabecular bone, bone density. Trabecular separation, and serum alkaline phosphatase ALP content.
  • infant refers to a person from 0 to 6 months of age.
  • infant refers to persons between the ages of 6 and 12 months.
  • young child refers to a person between the ages of 12 and 36 months.
  • infant refers to persons aged 0-36 months.
  • infant formula encompasses infant formula, follow-on formula and toddler formula.
  • infant formula is used as a substitute for breast milk from the time the baby is born
  • formula for older infants is used as a substitute for breast milk from 6 to 12 months after the baby is born
  • formula for young children is used as a substitute for breast milk from 12 to 36 months after the baby is born.
  • Breast milk substitutes are used as a substitute for breast milk from 12 to 36 months after the baby is born.
  • infant formula refers to liquid or powdered food that is produced and processed using only physical methods, using milk and milk protein products or soybeans and soybean protein products as the main raw materials, adding appropriate amounts of vitamins, minerals and/or other ingredients. product. It is suitable for normal infant consumption, and its energy and nutritional content can meet the normal nutritional needs of infants aged 0-6 months.
  • formula for older infants refers to liquid or food products that are produced and processed using only physical methods, using milk and milk protein products or soybeans and soybean protein products as the main raw materials, adding appropriate amounts of vitamins, minerals and/or other ingredients. Powdered product. It is suitable for consumption by older infants. Its energy and nutritional content can meet part of the nutritional needs of normal older infants aged 6-12 months.
  • young children's formula food refers to liquid or powdered food that is produced and processed using only physical methods, using milk and milk protein products or soybeans and soybean protein products as the main raw materials, adding appropriate amounts of vitamins, minerals and/or other ingredients. product. It is suitable for consumption by young children. Its energy and nutritional content can meet part of the nutritional needs of normal children between 12 and 36 months old.
  • breast milk is understood to mean the mother's breast milk or colostrum.
  • exclusive breastfed infant or young child has its usual meaning and refers to most Infants whose nutrients and/or energy are derived from human breast milk.
  • infant formula has a common meaning and refers to infant formula, older infants and toddlers whose nutritional sources of nutrients and/or energy are mainly derived from physical production and processing. Infant milk or growing milk for babies or toddlers.
  • the term “mainly” means at least 50%, such as at least 75%, of those nutrients and/or energy.
  • compositions of the present invention may comprise, consist of, or consist essentially of the following elements: the essential elements and essential limitations of the invention as described herein, and as described herein or any other or optional ingredients, components or limitations as otherwise required.
  • the individuals described in the present invention are suitable for normal humans, and can be infants and/or older infants, and/or young children, and/or children, and/or young people, and/or middle-aged people, and/or the elderly. More preferred are formula-fed human infants and young children.
  • the present invention relates to a nutritional composition for promoting skeletal development (such as human or animal body), especially for promoting skeletal development of infants and children, a food containing the nutritional composition, and the nutritional composition or food in promoting bone development. , especially for non-therapeutic purposes in promoting bone development in infants and children.
  • the invention provides a nutritional composition comprising:
  • HMO Human milk oligosaccharides
  • HMO neutral fucosylated human milk oligosaccharides
  • 2'-fucosyllactose (2'-FL) 3'-fucosyllactose Fucosyllactose (3'-FL)
  • lactose-N-fucopentose I LNFP I
  • lactose-N-difucohexaose I LNDFH I
  • LNDFH II lactose-N-difucohexaose II
  • HMOs Human milk oligosaccharides
  • Breast milk oligosaccharides HMO are the collective name for oligosaccharides with a degree of polymerization ⁇ 3 that occur naturally in breast milk. It On the basis of the lactose molecule, the terminal position is modified by five monomers, namely glucose (Glc), galactose (Gal), N-acetylglucosamine (GlcNAc), fucose (Fuc) and N-acetylneuramine. Acid (Neu5Ac).
  • HMOs Each HMO molecule contains 3 to 32 monosaccharides, which are connected through different glycosidic bonds, making up the diversity and complexity of HMOs.
  • HMOs can be divided into neutral fucosylated HMOs (which contain fucose at the terminal position), neutral non-fucosylated HMOs (containing N-acetylglucosamine at the terminal position), and acidic or
  • the ratios of three types of sialylated HMO (containing sialic acid at the end) in breast milk oligosaccharides are usually 35-50%, 42-55%, and 12-14% respectively.
  • 2'-Fucosyllactose (2'-FL) is a neutral trisaccharide composed of L-fucose, D-galactose and D-glucose units, in which the monosaccharide L-fucose passes through ⁇ (1 ⁇ 2) bond is connected to the disaccharide D-lactose.
  • Its molecular formula is C 18 H 31 O 15 , its molecular weight is 488.439g/mol, and its molecular structure is as follows.
  • 3'-Fucosyllactose is a neutral trisaccharide composed of L-fucose, D-galactose and D-glucose units, in which the monosaccharide L-fucose passes through ⁇ (1 ⁇ 3) bond is connected to D-glucose.
  • Its molecular formula is C 18 H 32 O 15 , its molecular weight is 488.44g/mol, and its molecular structure is as follows.
  • Lactose-N-fucopentose I is a neutral pentasaccharide composed of L-fucose, D-glucose, 2 molecules of D-galactose, and N-acetylglucosamine units, in which the monosaccharide L- Fucose is linked to D-glucose through an ⁇ (1 ⁇ 3) bond. Its molecular formula is C 32 H 55 NO 25 , its molecular weight is 853.77g/mol, and its molecular structure is as follows.
  • Lactose-N-difucohexaose I is a neutral hexasaccharide composed of 2 molecules of L-fucose, D-glucose, D-galactose, and N-acetylglucosamine units, in which the monosaccharide L -Fucose is connected to D-galactose and N-acetylglucosamine through ⁇ (1 ⁇ 2) and ⁇ (1 ⁇ 4) bonds respectively.
  • Its molecular formula is C 38 H 65 NO 29 , its molecular weight is 999.91g/mol, and its molecular structure is as follows.
  • Lactose-N-difucohexaose II is a neutral hexasaccharide composed of 2 molecules of L-fucose, D-glucose, D-galactose, and N-acetylglucosamine units, in which the monosaccharide L -Fucose is connected to D-glucose and N-acetylglucosamine through ⁇ (1 ⁇ 3) and ⁇ (1 ⁇ 4) bonds respectively.
  • Its molecular formula is C 38 H 65 NO 29 , its molecular weight is 999.91g/mol, and its molecular structure is as follows.
  • Arachidonic acid is an omega-6 polyunsaturated fatty acid, which is fully cis-5,8,11,14-eicosatetraenoic acid.
  • HMO human milk oligosaccharide
  • LNFP I lactose-N-fucopentose I
  • LNDFH I lactose-N-difucohexaose I
  • LNDFH II lactose-N-difucohexaose II
  • ARA arachidonic acid
  • the nutritional composition consists of:
  • HMO Human milk oligosaccharides
  • HMO neutral fucosylated human milk oligosaccharides
  • 2'-fucosyllactose (2'-FL) 3'-fucosyllactose Fucosyllactose (3'-FL)
  • lactose-N-fucopentose I LNFP I
  • lactose-N-difucohexaose I LNDFH I
  • LNDFH II lactose-N-difucohexaose II
  • the human milk oligosaccharide is a neutral fucosylated human milk oligosaccharide (HMO), which is preferably selected from 2'-fucosyllactose (2'-FL ), 3'-fucosyllactose (3'-FL), lactose-N-fucopentose I (LNFP I), lactose-N-difucohexaose I (LNDFH I), lactose-N- One or more of difucohexaose II (LNDFH II), preferably 2'-fucosyllactose (2'-FL).
  • HMO neutral fucosylated human milk oligosaccharide
  • the human milk oligosaccharide is 2'-fucosyllactose (2'-FL).
  • the human milk oligosaccharide (e.g., selected from 2'-fucosyllactose (2'-FL), 3'-fucosyllactose (3'-FL), Neutral fucosyl group of lactose-N-fucopentaose I (LNFP I), lactose-N-difucohexaose I (LNDFH I), lactose-N-difucohexaose II (LNDFH II)
  • Human milk oligosaccharides (HMOs), such as 2'-fucosyllactose (2'-FL) may be provided from natural sources, and/or synthetic sources, and/or bacterial fermentation sources.
  • the 2'-fucosyllactose content in each source can generally be 60-99.9% by mass, or any other content.
  • ARA arachidonic acid
  • breast milk oligosaccharides for example, selected from 2'-fucosyllactose (2'-FL) , 3'-fucosyllactose (3'-FL), lactose-N-fucopentose I (LNFP I), lactose-N-difucohexaose I (LNDFH I), lactose-N-di Neutral fucosylated human milk oligosaccharides (HMO) of fucohexaose II (LNDFH II), such as 2'-fucosyllactose (2'-FL) can be 0.01-10000, preferably 0.05- 5000, preferably 0.1-3000, preferably 0.3-1000, preferably 2-500, preferably 3-200 parts by mass, for example, it can be 0.01, 0.02, 0.03, 0.04, 0.05, 0.06, 0.07, 0.08, 0.09
  • ARA arachidonic acid
  • the nutritional composition may be used to promote bone development in humans or animals (eg, mammals).
  • human milk oligosaccharides for example, selected from 2'-fucosyllactose (2'-FL), 3'-fucosyllactose (3'-FL), lactose-N-fucopentan Neutral fucosylated human milk oligosaccharides (LNFP I), lactose-N-difucohexaose I (LNDFH I), lactose-N-difucohexaose II (LNDFH II) HMO), such as 2'-fucosyllactose (2'-FL)) and arachidonic acid (ARA) when the mass ratio is within the above range, can more significantly promote bone development (such as improving bone density, blood One or more or even all of the indicators related to bone development such as calcium and/or phosphorus absorption, relative volume of trabecular bone, thickness of trabecular bone, degree of separation
  • the components are effective in promoting bone development (such as improving bone density, absorption of calcium and/or phosphorus in the blood, relative volume of trabecular bone, thickness of trabecular bone, bone
  • the synergistic effect is more significant in terms of at least one of the indicators related to bone development such as trabecular separation and alkaline phosphatase ALP content in serum).
  • the invention also relates to a food product comprising said nutritional composition.
  • the food of the present invention may be in powder form or liquid form.
  • the food of the present invention can be infant formula food (such as infant formula food, older infant formula food Prescription foods, infant formula foods) such as infant formula milk powder (such as infant formula milk powder, infant formula milk powder), infant food supplements, nutritional or dietary supplements, or milk powder prepared for pregnant women.
  • infant formula food such as infant formula food, older infant formula food Prescription foods, infant formula foods
  • infant formula milk powder such as infant formula milk powder, infant formula milk powder
  • infant food supplements such as infant formula milk powder, infant food supplements, nutritional or dietary supplements, or milk powder prepared for pregnant women.
  • the nutritional composition is added in an amount such that, relative to the total mass of the food, breast milk oligosaccharides (for example, selected from 2'-fucosyllactose (2'-FL), 3 '-Fucosyllactose (3'-FL), lactose-N-fucopentose I (LNFP I), lactose-N-difucohexaose I (LNDFH I), lactose-N-difucose
  • the mass content of neutral fucosylated human milk oligosaccharides (HMO) of hexasaccharide II (LNDFH II), such as 2'-fucosyllactose (2'-FL) is at least 0.005%, preferably at least 0.01%, preferably at least 0.05%, and preferably up to 20.0%, preferably up to 10.0%.
  • human milk oligosaccharides e.g., selected from 2'-fucosyllactose (2'-FL), 3'-fucosyllactose (3'-FL), lactose -Neutral fucosylation of N-fucopentaose I (LNFP I), lactose-N-difucohexaose I (LNDFH I), lactose-N-difucohexaose II (LNDFH II)
  • the mass content of breast milk oligosaccharides (HMO), such as 2'-fucosyllactose (2'-FL) can be 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%,
  • the nutritional composition is added in an amount such that, relative to the total mass of the food, the mass content of arachidonic acid is at least 0.0005%, preferably at least 0.001%, preferably at least 0.003%, and preferably Up to 1.0%, preferably up to 0.5%.
  • the mass content of arachidonic acid can be 0.0005%, 0.0006%, 0.0007%, 0.0008%, 0.0009%, 0.0010%, 0.0015%, 0.0020%, 0.0025%, 0.0030%, 0.0035%, 0.0040%, 0.0045%, 0.0050%, 0.0055%, 0.0060%, 0.0065%, 0.0070%, 0.0075%, 0.0080%, 0.0085%, 0.0090%, 0.0095%, 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%, 0.10%, 0.11%, 0.12 %, 0.13%, 0.14%, 0.15%, 0.16%, 0.17%, 0.18%, 0.19%, 0.20%, 0.21%, 0.21%, 0.25%, 0.25%,
  • human milk oligosaccharides for example, selected from 2'-fucosyllactose (2'-FL), 3'-fucosyllactose (3'-FL), lactose-N-fucopentan Neutral fucosylated human milk oligosaccharides ( HMO), such as 2'-fucosyllactose (2'-FL)
  • HMO Neutral fucosylated human milk oligosaccharides
  • arachidonic acid when the mass content is within the above range
  • HMO Neutral fucosylated human milk oligosaccharides
  • arachidonic acid when the mass content is within the above range
  • the synergistic effect is more significant; and at the same time, it can balance various aspects of nutrition (such as those needed by the human body or animals).
  • the nutritional composition is added in an amount such that the human milk oligosaccharide (for example, selected from 2'-fucosyllactose (2'-FL), 3'-fucose) in the food Lactose (3'-FL), lactose-N-fucopentose I (LNFP I), lactose-N-difucohexaose I (LNDFH I), lactose-N-difucohexaose II (LNDFH II)
  • the mass ratio of neutral fucosylated human milk oligosaccharides (HMO), such as 2'-fucosyllactose (2'-FL)) and arachidonic acid is 2-300:1, Preferably 3-200:1, or any other value or range within this range mentioned above (in the nutritional composition section), and relative to the total mass of the food product, the human milk oligosaccharides (e.g.
  • the amount of 2'-FL)) is at least 0.05%, preferably at least 0.06%, and preferably at most 10%, preferably at most 6%, preferably at most 3%, or any other value within this range mentioned above or scope.
  • the nutritional composition is added in an amount such that, relative to the total mass of the food, the amount of arachidonic acid is at least 0.0025%, preferably at least 0.0030%, preferably at least 0.0035%, And preferably up to 1%, preferably up to 0.6%, preferably up to 0.3%, or any other value or range mentioned above within this range.
  • the ratio and amount of breast milk oligosaccharides such as 2'-fucosyllactose (2'-FL) and arachidonic acid are within the above range or within the preferred range, these two components promote bone health, In particular, the synergistic effect in increasing bone density is more significant.
  • the food may also contain other ingredients, such as proteins/amino acids, carbohydrates, fats, vitamins, minerals, etc. in formula foods such as infant formulas such as Ingredients often found in milk powder.
  • the present invention relates to the non-therapeutic use of the above-mentioned nutritional composition or the above-mentioned food in promoting bone development, especially in promoting bone development in infants and children.
  • the promotion of bone development includes improving at least one of the following (indicators related to bone development): bone density, absorption of calcium and/or phosphorus in the blood, relative volume of trabecular bone, Trabecular bone thickness, trabecular separation, and serum alkaline phosphatase ALP content.
  • the promotion of skeletal development includes: promoting skeletal development of human bodies, especially skeletal development of infants and children; and/or promoting skeletal development of animals, especially mammals.
  • Alkaline phosphatase kit (211026101), calcium/phosphorus kit (201102301/210305101): Meikang Biotechnology Co., Ltd.;
  • ARA Arachidonic acid
  • Refrigerator BCD-160TMPQ Qingdao Haier Co., Ltd.
  • Vortex oscillator VS-10M Weiwosoko Technology Beijing Co., Ltd.
  • mice Purchase approximately 228 young (4 weeks old) male C56BL/6 mice in stable health condition, SPF grade. Breeding environment: room temperature 20-25°C, alternating light and dark every 12 hours, relative humidity of about 50%, uniform matching of feed and drinking water, keeping the indoor environment well ventilated, cleaning every day, and maintaining a good hygienic environment in the cage; Animal welfare: During the entire process of the experiment, mice were treated with reasonable means, in compliance with the relevant regulations of the Laboratory Animal Ethics Committee, and specifically in accordance with the IAC category and other relevant standard operating procedures (SOP); killing method: mice that were removed after the experiment were First, the body was killed by anesthesia and abdominal artery bleeding, then the body was stored in a special freezer container, and finally, it was disposed of harmlessly.
  • SOP Standard operating procedures
  • mice were anesthetized with 1% sodium pentobarbital and fixed on a small animal in vivo tomography imager with a resolution of 20 ⁇ m. After the scan, image reconstruction was performed, and Inveon Research Workplace 2.2 software was used to analyze the bone density of mice in each group. , relative volume of trabecular bone (Tb.BV/TV), relative number of trabecular bone (Tb.N), trabecular bone separation (Tb.Sp), etc.
  • Tb.BV/TV relative volume of trabecular bone
  • Tb.N relative number of trabecular bone
  • Tb.Sp trabecular bone separation
  • mice In order to evaluate the effect of the test substances alone or mixed on the bone health of mice, the bone density of mice in each group was measured, as shown in Table 2.
  • each embodiment significantly increases bone density. Bone density is an important indicator of bone health, indicating that each embodiment can promote bone development and health.
  • ARA and 2'-FL have a synergistic effect when used in combination, and can synergistically promote bone development and health, such as increasing bone density.
  • Experimental Example 2 is equivalent to the combination of Comparative Examples 2 and 6. Compared with the blank control group, Example 2, Comparative Example 2, and Comparative Example 6 respectively increased bone density. 88.57, 50.47, 18.22. The increment of bone density in Example 2 (88.57) is greater than the sum of the respective increments of Comparative Examples 2 and 6 (68.69).
  • Experimental Example 3 is equivalent to the combination of Comparative Examples 3 and 5. Compared with the blank control group, Example 3, Comparative Example 3, and Comparative Example 5 increased the bone density by 89.57, 60.56, and 18.12 respectively. The bone density in Example 3 The increment (89.57) is greater than the sum of the respective increments of Comparative Examples 3 and 5 (78.68).
  • Experimental Example 7 is equivalent to the combination of Comparative Examples 3 and 6. Compared with the blank control group, Example 7, Comparative Example 3, and Comparative Example 6 increased the bone density by 90.2, 60.56, and 18.22 respectively. The bone density in Example 7 The increment (90.2) is greater than the sum of the respective increments of Comparative Examples 3 and 6 (78.78).
  • mice In order to evaluate the effects of the test substances alone or mixed on the bones of mice, the trabecular bone of mice in each group was measured, as shown in Tables 3, 4, and 5.
  • Relative volume of trabecular bone (Bv/Tv), this ratio can reflect the amount of trabecular bone mass in different samples. An increase in this value indicates that bone anabolism is greater than catabolism, and bone mass increases, and vice versa, which can indirectly reflect bone metabolism. situation.
  • each embodiment can significantly increase the relative volume of trabecular bone, thereby indicating that each embodiment can promote bone development and health.
  • ARA and 2'-FL have a synergistic effect when used in combination, and can synergistically promote bone development and health, such as increasing the relative volume of trabecular bone.
  • Experimental Example 4 is equivalent to the combination of Comparative Examples 1 and 5.
  • Example 4 Comparative Example 1, and Comparative Example 5 respectively make trabecular bone relatively
  • the volume increased by 0.026, 0.009, and 0.016.
  • the increase in relative volume of trabecular bone in Example 4 (0.026) was greater than the sum of the respective increases in Comparative Examples 1 and 5 (0.025).
  • Example 5 is equivalent to the combination of Comparative Examples 2 and 4. Compared with the blank control group, Example 5, Comparative Example 2, and Comparative Example 4 increased the relative volume of trabecular bone by 0.027, 0.009, and 0.006 respectively. Example 5 The increment in the relative volume of trabecular bone (0.027) is greater than the sum of the increments in Comparative Examples 2 and 4 (0.015).
  • Trabecular thickness (Tb.Th) and trabecular separation (trabecular separation, Tb.Sp) is the main index to evaluate the spatial morphological structure of trabecular bone.
  • Tb/Th value decreases; the Tb/Sp value increases.
  • each embodiment can significantly increase the thickness of trabecular bone and significantly reduce the separation of trabecular bone, thereby indicating that each embodiment can significantly promote bone development and health.
  • ARA and 2'-FL have a synergistic effect when used in combination and can synergistically promote bone development and health, such as increasing trabecular bone thickness.
  • Experimental Example 1 is equivalent to the combination of Comparative Examples 1 and 6.
  • Example 1 Comparative Example 1 and Comparative Example 6 respectively increased the thickness of trabecular bone.
  • the increases were 0.0026, 0.0005, and 0.0005.
  • the increase in trabecular bone thickness in Example 1 (0.0026) was greater than the sum of the respective increases in Comparative Examples 1 and 6 (0.001).
  • Example 4 is equivalent to the combination of Comparative Examples 1 and 5. Compared with the blank control group, Example 4, Comparative Example 1 and Comparative Example 5 increased the thickness of trabecular bone by 0.0012, 0.0005 and 0.0002 respectively. In Example 4 The increase in trabecular bone thickness (0.0012) was greater than the sum of the respective increases in Comparative Examples 1 and 5 (0.0007).
  • Example 6 is equivalent to the combination of Comparative Examples 3 and 4. Compared with the blank control group, Example 6, Comparative Example 3 and Comparative Example 4 increased the thickness of trabecular bone by 0.0033, 0.0015 and 0.001 respectively. In Example 6 The increase in trabecular bone thickness (0.0033) was greater than the sum of the respective increases in Comparative Examples 3 and 4 (0.0025).
  • Example 7 is equivalent to the combination of Comparative Examples 3 and 6. Compared with the blank control group, Example 7, Comparative Example 3 and Comparative Example 6 increased the thickness of trabecular bone by 0.0033, 0.0015 and 0.0005 respectively. In Example 7 The increase in trabecular bone thickness (0.0033) was greater than the sum of the respective increases in Comparative Examples 3 and 6 (0.002).
  • mice In order to evaluate the effect of test substances alone or mixed treatment on bone metabolism in mice, the alkaline phosphatase in the serum of mice in each group was measured, as shown in Table 6.
  • ALP is mainly synthesized and secreted by osteoblasts and liver, and is an important indicator reflecting bone metabolism. It is secreted by osteoblasts when osteogenesis is active. 50% of ALP in serum is secreted by osteogenesis. Therefore, to a certain extent, serum ALP levels reflect changes in bone metabolism. Relevant research results show that when rapid bone loss occurs in the body or there is a risk of fracture, the serum ALP level in the body increases significantly. The reason may be an increase in bone resorption, leading to compensatory bone formation and enhanced bone turnover.
  • sample processing results show that compared with the blank control group, each embodiment significantly reduces the content of alkaline phosphatase, indicating that each embodiment can reduce alkaline phosphatase activity, improve bone metabolism, and thereby promote bone development and health.
  • ARA and 2'-FL have a synergistic effect when used in combination, and can synergistically promote bone development and health, such as synergistically reducing the content of alkaline phosphatase in serum and improving bone metabolism.
  • Experimental Example 3 is equivalent to the combination of Comparative Examples 3 and 5.
  • Example 3, Comparative Example 3, and Comparative Example 5 respectively make alkaline phosphatase
  • the reductions were 12.90, 10.90, and 1.47.
  • the reduction in alkaline phosphatase in Example 3 (12.90) was greater than the sum of the respective reductions in Comparative Examples 3 and 5 (12.37).
  • Example 4 is equivalent to the combination of Comparative Examples 1 and 5. Compared with the blank control group, Example 4, Comparative Example 1, and Comparative Example 5 reduced alkaline phosphatase by 6.85, 3.30, and 1.47 respectively. In Example 4 The reduction in alkaline phosphatase (6.85) was greater than the sum of the respective reductions in Comparative Examples 3 and 6 (4.77).
  • Example 6 is equivalent to the combination of Comparative Examples 3 and 4. Compared with the blank control group, Example 6, Comparative Example 3, and Comparative Example 4 reduced alkaline phosphatase by 18.20, 10.90, and 4.83 respectively. In Example 7 The reduction in alkaline phosphatase (18.20) was greater than the sum of the respective reductions in Comparative Examples 3 and 6 (15.73).
  • Experimental Example 7 is equivalent to the combination of Comparative Examples 3 and 6. Compared with the blank control group, Example 7, Comparative Examples 3 and 6 reduced alkaline phosphatase by 20.59, 10.90, and 7.73 respectively. The reduction in alkaline phosphatase in Example 7 (20.59) was greater than the sum of the respective reductions in Comparative Examples 3 and 6 (18.63).
  • Calcium and phosphorus are the main elements that make up bones and coordinate with each other in building bones.
  • sample processing results show that compared with the blank control group, each example significantly increased the contents of Ca and P in the serum, indicating that the two components can coordinate with each other in bone building, increase the absorption of Ca and P, thereby promoting bone Development and health.
  • ARA and 2'-FL have a synergistic effect when used in combination, and can synergistically promote bone development and health, for example, can synergistically increase the levels of Ca and P in serum.
  • Example 3 is equivalent to the combination of Comparative Examples 3 and 5.
  • Comparative Example 3 and Comparative Example 5 respectively make the concentration of Ca in serum The content increased by 0.22, 0.13, and 0.07, and the increment of Ca in Example 3 (0.22) was greater than the sum of the respective increments of Comparative Examples 3 and 5 (0.20).
  • Example 4 is equivalent to the combination of Comparative Examples 1 and 5. Compared with the blank control group, Example 4, Comparative Example 1 and Comparative Example 5 respectively increased the Ca content in serum by 0.13, 0.05 and 0.07. Example 4 The increment of Ca (0.13) is greater than the sum of the respective increments of Comparative Examples 1 and 5 (0.12).
  • the present invention provides breast milk oligosaccharides such as 2'-fucosyllactose (2'-FL), eicosadonic acid (ARA) compositions are beneficial in bone development and health, for example, in improving bone density, calcium and/or phosphorus absorption in the blood, trabecular relative volume, trabecular thickness, trabecular separation, and alkaline phosphatase in serum Research on indicators related to bone development such as ALP content provides new ideas for the development of functional foods in the future.
  • Breast milk oligosaccharides such as 2'-fucosyllactose (2'-FL) and arachidonic acid (ARA) have broad prospects in promoting bone development. Studies have found that they have greater potential in improving bone development and health. Good synergy.
  • DHA Docosahexaenoic acid
  • Infant formula milk powder containing 2’-fucosyllactose (2’-FL) and arachidonic acid (ARA) is prepared from the following mass parts per 1,000 parts of infant formula milk powder:
  • the raw materials used in the milk powder of the present invention include: 180 parts of whole milk powder (each part contains 0.08% eicosadonic acid), 8.3 parts of 2'-fucosyllactose (each part contains 2'-fucosyllactose 96.0%), 15 parts of eicosadonic acid oil powder (10% of eicosadonic acid in each part), 400 parts of desalted whey powder, 119.95 parts of lactose, 50 parts of galacto-oligosaccharide, and 190 parts of mixed vegetable oil , 15 parts of docosahexaenoic acid oil powder, 3 parts of sodium citrate, 3 parts of potassium chloride, 3 parts of calcium carbonate, 4 parts of calcium hydrogen phosphate, 3 parts of compound vitamins, 2 parts of compound minerals, Formulated with 1 part of nutrients, 2.1 parts of compound chlorinated arachidonic acid, and 0.65 parts of compound nucleotides; after mixing the above raw materials evenly, they are pasteurized, homogen
  • Infant formula milk powder containing 2’-fucosyllactose (2’-FL) and eicosadonic acid (ARA) is prepared from the following mass parts per 1,000 parts of infant formula milk powder:
  • the raw materials used in the milk powder of the present invention include: 231.8 parts of raw milk in terms of solid content (each part contains 0.08% eicosadonic acid), 0.83 parts of 2'-fucosyllactose (each part contains 2'-fucosylated lactose) Glycosylated lactose 96.0%), 2 parts eicosadonic acid oil powder (each part contains 10% eicosadonic acid), 275 parts desalted whey powder, 166.12 parts lactose, 125 parts skimmed milk powder, oligomer 50 parts of galactose, 130 parts of mixed vegetable oil, 4 parts of docosahexaenoic acid oil powder, 1 part of sodium citrate, 1 part of potassium chloride, 3.5 parts of calcium carbonate, 1 part of calcium hydrogen phosphate, 3 parts of multivitamins , 2 parts of compound minerals, 1 part of compound nutrients, 2.1 parts of compound chlorinated arachidonic acid, and 0.65 parts of
  • the raw materials used in the milk powder of the present invention include: 231.8 parts of raw milk in terms of solid content (each part contains 0.08% eicosadonic acid), 8.3 parts of 2'-fucosyllactose (each part contains 2'-fucosyllactose) Glycosylated lactose 96.0%), 2 parts eicosadonic acid oil powder (each part contains 10% eicosadonic acid), 275 parts desalted whey powder, 158.65 parts lactose, 125 parts skimmed milk powder, oligomer 50 parts of galactose, 130 parts of mixed vegetable oil, 4 parts of docosahexaenoic acid oil powder, 1 part of sodium citrate, 1 part of potassium chloride, 3.5 parts of calcium carbonate, 1 part of calcium hydrogen phosphate, 3 parts of multivitamins , 2 parts of compound minerals, 1 part of compound nutrients, 2.1 parts of compound chlorinated arachidonic acid, and 0.65 parts of compound
  • Modulated milk powder containing 2’-fucosyllactose (2’-FL) and arachidonic acid (ARA) is suitable for pregnant women.
  • Each 1,000 parts of the modified milk powder is prepared from the following mass parts:
  • the raw materials used in the milk powder of the present invention include: 590 parts of skimmed milk powder, 0.83 parts of 2'-fucosyllactose (96.0% of 2'-fucosyllactose in each part), and 0.8 parts of eicosadonic acid oil powder. (Eicosadonic acid 10% per serving), 96 parts of vegetable oil, 74.37 parts of lactose, 195 parts of solid corn syrup, 40 parts of isomaltooligosaccharide, 2 parts of compound vitamins, 1 part of compound minerals; combine the above After the raw materials are mixed evenly, they are pasteurized, homogenized, evaporated, concentrated and spray-dried into powdery semi-finished products. The evenly mixed milk powder is filled with nitrogen and packaged to obtain the final product. The content of 2’-fucosyllactose in the product is 0.08% and eicosadonic acid is 0.008%.
  • Modulated milk powder containing 2'-fucosyllactose (2'-FL) and arachidonic acid (ARA) is suitable for consumption by middle-aged and elderly people.
  • Each 1,000 parts of the modified milk powder is made of the following mass parts have to:
  • the raw materials used in the milk powder of the present invention include: 436 parts of whole milk powder (each part contains 0.08% eicosadonic acid), 86.34 parts of 2'-fucosyl lactose (each part contains 2'-fucosyl lactose Lactose 96.0%), 17 parts of eicosadonic acid oil powder (each part contains 10% of eicosadonic acid), 250 parts of skim milk powder, 172.66 parts of solid corn syrup, 35 parts of isomaltooligosaccharide, compound 2 parts of vitamins and 1 part of compound minerals; after mixing the above raw materials evenly, pasteurize, homogenize, evaporate, concentrate and spray dry them into a semi-powder
  • the finished product is obtained by filling the uniformly mixed milk powder with nitrogen and packaging.
  • the content of 2'-fucosyllactose in the product is 8.3% and eicosadonic acid is 0.2%.
  • Modulated milk containing 2’-fucosyllactose (2’-FL) and arachidonic acid (ARA) is prepared from the following mass parts per 1,000 parts of modified milk:
  • the prepared milk of the present invention consists of 903.86 parts of raw milk (each part contains 0.01% eicosadonic acid), 83.34 parts of 2'-fucosyllactose (96.0% of 2'-fucosyllactose per part), 3 parts of eicosatetraenoic acid oil powder (each part contains 10% ARA), 9.3 parts of fructooligosaccharides, and 0.5 parts of mono- and diglyceryl fatty acid esters; mix the above raw materials, homogenize, UHT sterilize, homogenize, and sterile Filling is the final product.
  • the content of 2’-fucosyllactose in the product is 8% and arachidonic acid (ARA) is 0.04%.

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Abstract

营养组合物、包含其的食品以及该营养组合物的用途。营养组合物包含：母乳低聚糖，例如中性岩藻糖基化的母乳低聚糖，优选选自2'-岩藻糖基乳糖、3'-岩藻糖基乳糖、乳糖-N-岩藻五糖I、乳糖-N-二岩藻六糖I、乳糖-N-二岩藻六糖II；和花生四烯酸。营养组合物能够促进骨骼发育，尤其是促进婴幼儿及儿童骨骼发育。

Description

营养组合物、包含其的食品以及该营养组合物的用途 技术领域
本发明总体上涉及食品领域。具体地，本发明涉及一种用于促进骨骼发育的营养组合物，包含该营养组合物的食品，以及该营养组合物或食品的用途。更具体地，本发明涉及一种包含母乳低聚糖(例如选自2’-岩藻糖基乳糖(2’-FL)、3’-岩藻糖基乳糖(3’-FL)、乳糖-N-岩藻五糖I(LNFP I)、乳糖-N-二岩藻六糖I(LNDFH I)、乳糖-N-二岩藻六糖II(LNDFH II)的中性岩藻糖基化的母乳低聚糖(HMO)，例如2’-岩藻糖基乳糖(2’-FL))和花生四烯酸(ARA)的营养组合物，包含该营养组合物的食品，以及所述营养组合物或食品用于促进骨骼发育，尤其是促进婴幼儿及儿童骨骼发育的非治疗目的的用途。
背景技术
骨是一种高活性结缔组织，可以通过骨代谢及骨重塑来修复自身微损伤，保持骨结构、荷载及钙含量的内稳态平衡，同时骨也作为内分泌器官调控代谢过程，是维持人体生命的重要器官。从新生儿时期开始，骨量随年龄的增长而增加，直到青年时期骨发育成熟，骨量达到峰值。研究发现，青少年时期注意提高骨量，能够在青年时期获得个体峰值骨量。因而青少年时期骨的生长发育对骨的成熟至关重要。有研究指出，青少年时期的骨密度(Bonemineral density，BMD)决定了成年后的骨量峰值和随后的骨丢失速率。BMD降低会导致骨量不足，从而引发佝偻病、软骨病等一系列骨疾病，严重影响青少年的骨健康。在这一时期，营养的补充是影响骨量峰值的重要因素，摄入营养物质能够提高骨量峰值，促进骨的形成。因此寻求一种天然的功能性营养物质来提高青少年BMD，增加骨形成，对提高骨量、预防青少年骨折与中老年骨质疏松症等骨疾病以及维持骨健康有着重要意义。
骨包含细胞外蛋白基质(类骨质)，其中散布着骨细胞且由钙盐和其它矿物质组成的矿物质成分位于细胞外基质内。骨经历重吸收过程的重塑，在这种情况下骨通过破骨细胞降解然后被成骨细胞所取代(再形成)。重塑的发生调节钙体内平衡、修复日常应力损伤的骨以及生长或机械应力模式变化时使 骨成形。破骨细胞使特定区域内的骨降解然后经历细胞凋亡。成骨细胞重建新骨而且介导它的再矿化作用。在再矿化作用期间，一些成骨细胞被包在钙化物质内然后变成骨细胞。
一旦在婴儿至成年早期已达到骨含量峰值，重吸收过程就几乎完全伴随着再形成。然而，随着人老龄化，重塑系统的有效调节变弱。随着女性更年期的开始，这两个过程就可能变得失去同步性，其中重吸收占主导地位。此外，随着老龄化会有骨矿物质密度流失、骨微结构破坏和其他的变化，这些都导致了骨折风险增加。骨质流失的过程经常是逐渐的，在疾病适当进展之前并没有明显的症状呈现。因此随着时间的推移维持骨质量和密度是重要的，这样使骨不会随着老龄化而变得脆弱。
因此，需要提供一种能够促进骨骼发育、尤其是能够促进婴幼儿及儿童骨骼发育的营养组合物。
发明内容
本发明的一个目的是提供一种能够促进骨骼发育、尤其是促进婴幼儿及儿童骨骼发育的营养组合物。
本发明的另一目的是提供一种含有该营养组合物的食品。
本发明的另一目的是提供所述营养组合物或食品在促进(例如人体或动物体)骨骼发育(例如改善如下的至少一种：骨密度、血液中钙和/或磷的吸收、骨小梁相对体积、骨小梁厚度、骨小梁分离度、血清中碱性磷酸酶ALP含量等与骨骼发育相关的指标)、尤其是促进婴幼儿及儿童骨骼发育中的非治疗目的的用途。
本发明人研究发现，通过将母乳低聚糖(例如选自2’-岩藻糖基乳糖(2’-FL)、3’-岩藻糖基乳糖(3’-FL)、乳糖-N-岩藻五糖I(LNFP I)、乳糖-N-二岩藻六糖I(LNDFH I)、乳糖-N-二岩藻六糖II(LNDFH II)的中性岩藻糖基化的母乳低聚糖(HMO)，例如2’-岩藻糖基乳糖(2’-FL))和花生四烯酸(ARA)组合使用，可以协同促进骨骼发育和健康(例如就骨密度、血液中钙和/或磷的吸收、骨小梁相对体积、骨小梁厚度、骨小梁分离度、碱性磷酸酶ALP等与骨骼发育和健康相关的指标而言，协同改善其至少一种)。这些发现使这两种成分的潜在应用范围意料地扩大，无论是作为药物，还是以食物活营养或膳食补充剂的形式，适合于改善骨骼发育。
特别地，本发明通过如下实现：
1.一种营养组合物，其包括如下或者由如下组成：
-母乳低聚糖，优选中性岩藻糖基化的母乳低聚糖，其优选地选自2’-岩藻糖基乳糖、3’-岩藻糖基乳糖、乳糖-N-岩藻五糖I、乳糖-N-二岩藻六糖I、乳糖-N-二岩藻六糖II中的一种或多种，优选2’-岩藻糖基乳糖；和
-花生四烯酸。
2.如条目1所述的营养组合物，其中母乳低聚糖以天然来源，和/或合成来源，和/或细菌发酵来源的形式提供。
3.如条目1-2任一项所述的营养组合物，其中：
相对于1质量份的花生四烯酸，母乳低聚糖的量为0.01-10000、优选0.05-5000、优选0.1-3000、优选0.3-1000、优选2-500、优选3-200质量份。
4.食品，其包含如条目1-3任一项所述的营养组合物。
5.如条目4所述的食品，其中所述食品为粉末或者液体形式。
6.如条目4-5任一项所述的食品，其为婴幼儿配方食品例如婴儿配方食品、较大婴儿配方食品、幼儿配方食品，例如婴幼儿配方奶粉，例如婴儿配方奶粉、幼儿配方奶粉；婴儿辅食；营养或膳食补充剂；或孕妇调制奶粉。
7.如条目4-6任一项所述的食品，其中所述营养组合物的添加量使得，相对于所述食品的总质量：
母乳低聚糖的质量含量为至少0.005％、优选至少0.01％、优选至少0.05％，且优选至多20.0％、优选至多10.0％，和
花生四烯酸的质量含量为至少0.0005％、优选至少0.001％、优选至少0.003％，且优选至多1.0％、优选至多0.5％。
8.如条目4-7任一项所述的食品，其中所述营养组合物的添加量使得，相对于所述食品的总质量：
母乳低聚糖的质量含量为至少0.05％、优选至少0.06％，且优选为至多10％、优选至多6％、优选至多3％，和
花生四烯酸的质量含量为至少0.0025％、优选至少0.0030％，且优选至多1％、优选至多0.6％、优选至多0.3％；
其中母乳低聚糖和花生四烯酸的质量比为2-300∶1、优选3-200∶1。
9.如条目1-3任一项所述的营养组合物或者如条目4-8任一项所述的食品在促进骨骼发育，尤其是促进婴幼儿及儿童骨骼发育中的非治疗目的的用 途。
10.如条目9所述的用途，其中所述促进骨骼发育包括改善如下的至少一种：骨密度、血液中钙和/或磷的吸收、骨小梁相对体积、骨小梁相对数目、骨小梁分离度、和血清中碱性磷酸酶ALP含量。
具体实施方式
如无特殊说明，本说明书中的科技术语的含义与本领域技术人员一般理解的含义相同，但如有冲突，则以本说明书中的定义为准。
如本文所用，下列术语具有如下含义。
术语″婴儿″是指0～6月龄的人。
术语″较大婴儿″是指6～12月龄的人。
术语″幼儿″是指12～36月龄的人。
术语″婴幼儿″是指0-36个月龄的人。
本文中使用的术语″婴幼儿配方食品″涵盖婴儿配方食品、较大婴儿配方食品和幼儿配方食品。通常，婴儿配方食品从婴儿出生起作为母乳替代品，较大婴儿配方食品是从婴儿出生后的6-12个月作为母乳替代品，幼儿配方食品指从婴儿出生后的12-36个月作为母乳替代品。
术语″婴儿配方食品″是指以乳类及乳蛋白制品或大豆及大豆蛋白制品为主要原料，加入适量维生素、矿物质和/或其它成分，仅用物理方法生产加工制成的液态或粉状产品。适用于正常婴儿食用，其能量和营养成分能够满足0-6个月婴儿的正常营养需要。
术语″较大婴儿配方食品″是指以乳类及乳蛋白制品或大豆及大豆蛋白制品为主要原料，加入适量维生素、矿物质和/或其它成分，仅用物理方法生产加工制成的液态或粉状产品。适用于较大婴儿食用，其能量和营养成分能够满足6-12个月正常较大婴儿的部分营养需要。
术语″幼儿配方食品″是指以乳类及乳蛋白制品或大豆及大豆蛋白制品为主要原料，加入适量维生素、矿物质和/或其它成分，仅用物理方法生产加工制成的液态或粉状产品。适用于幼儿食用，其能量和营养成分能够满足12-36个月正常幼儿的部分营养需要。
术语″母乳″应理解为母亲的母乳或初乳。
术语″完全用母乳喂养的婴儿或幼儿″具有通常的含义，指绝大部分营 养物质和/或能量源于人类母乳的婴儿。
术语″主要用婴幼儿配方食品喂养的婴儿/较大婴儿/幼儿″具有通常的含义，指营养物质和/或能量的营养源主要源于物理方法生产加工制成的婴幼儿配方食品、较大婴儿乳或成长乳的婴儿或幼儿。术语″主要″是指至少50％、例如至少75％的那些营养物质和/或能量。
另外，在本发明的上下文中，术语″包含″或″包括″不排除其它可能的要素。本发明的组合物(包括本文所述的多个实施方案)可包含下列要素、由下列要素组成或基本上由下列要素组成：本文所述的本发明的基本要素和必要限制，以及本文所述的或另外视需求而定的任何其它或任选的成分、组分或限制。
本发明所述个体适用于正常人类，可以是婴儿和/或较大婴儿、和/或幼儿、和/或儿童、和/或青年人、和/或中年人、和/或老年人。更优选的是配方食品喂养的人类婴幼儿。
除非另外指明，否则所有百分比均按质量计。
现在开始更详细描述本发明。应当注意，本申请描述的各个方面、特征、实施方式、实施例以及其优点可以相容和/或可以组合在一起。
本发明涉及用于促进(例如人体或动物体)骨骼发育、尤其是促进婴幼儿及儿童骨骼发育的营养组合物，包含该营养组合物的食品，以及所述营养组合物或食品在促进骨骼发育，尤其是促进婴幼儿及儿童骨骼发育中的非治疗目的的用途。
以下将对本发明进行具体说明。
营养组合物
在一个方面中，本发明提供了一种营养组合物，其包括：
-母乳低聚糖(HMO)，优选中性岩藻糖基化的母乳低聚糖(HMO)，其优选地选自2’-岩藻糖基乳糖(2’-FL)、3’-岩藻糖基乳糖(3’-FL)、乳糖-N-岩藻五糖I(LNFP I)、乳糖-N-二岩藻六糖I(LNDFH I)、乳糖-N-二岩藻六糖II(LNDFH II)中的一种或多种，优选2’-岩藻糖基乳糖(2’-FL)；和
-花生四烯酸。
母乳低聚糖(HMO)是母乳中含量仅次于乳糖和脂类的第三大类固体成分。母乳低聚糖HMO是母乳中天然存在的聚合度≥3的低聚糖的统称。它 是在乳糖分子的基础上终端位置由5种单体进行修饰，即葡萄糖(Glc)、半乳糖(Gal)、N-乙酰氨基葡萄糖(GlcNAc)、岩藻糖(Fuc)和N-乙酰神经氨酸(Neu5Ac)。HMO每个分子包含3至32个单糖，这些单糖通过不同的糖苷键加以连接，构成了HMO的多样性和复杂性。HMO基于其核心结构可分为中性岩藻糖基化HMO(其在末端位置含有岩藻糖)、中性非岩藻糖基化的HMO(末端含有N-乙酰氨基葡萄糖)、和酸性或唾液酸化的HMO(末端含有唾液酸)三种类型，其在母乳低聚糖中的比率通常分别为35-50％、42-55％、和12-14％。
2’-岩藻糖基乳糖(2’-FL)为由L-岩藻糖、D-半乳糖和D-葡萄糖单元组成的中性三糖，其中单糖L-岩藻糖通过α(1→2)键与二糖D-乳糖相连。其分子式为C18H31O15，分子量为488.439g/mol，分子结构如下。
3’-岩藻糖基乳糖(3’-FL)为由L-岩藻糖、D-半乳糖和D-葡萄糖单元组成的中性三糖，其中单糖L-岩藻糖通过α(1→3)键与D-葡萄糖相连。其分子式为C18H32O15，分子量为488.44g/mol，分子结构如下。
乳糖-N-岩藻五糖I(LNFP I)为由L-岩藻糖、D-葡萄糖、2分子D-半乳糖、N-乙酰氨基葡萄糖单元组成的中性五糖，其中单糖L-岩藻糖通过α(1→3)键与D-葡萄糖相连。其分子式为C32H55NO25，分子量为853.77g/mol，分子结构如下。
乳糖-N-二岩藻六糖I(LNDFH I)为由2分子L-岩藻糖、D-葡萄糖、D-半乳糖、N-乙酰氨基葡萄糖单元组成的中性六糖，其中单糖L-岩藻糖通过α(1→2)键、α(1→4)键分别与D-半乳糖、N-乙酰氨基葡萄糖相连。其分子式为C38H65NO29，分子量为999.91g/mol，分子结构如下。
乳糖-N-二岩藻六糖II(LNDFH II)为由2分子L-岩藻糖、D-葡萄糖、D-半乳糖、N-乙酰氨基葡萄糖单元组成的中性六糖，其中单糖L-岩藻糖通过α(1→3)键、α(1→4)键分别与D-葡萄糖、N-乙酰氨基葡萄糖相连。其分子式为C38H65NO29，分子量为999.91g/mol，分子结构如下。
花生四烯酸(ARA)是一种ω-6多不饱和脂肪酸，是全顺式-5，8，11，14-二十碳四烯酸，化学式如下：CH3(CH2)4(CH＝CH-CH2)4(CH2)2COOH，属于不饱和脂肪酸，其中含有四个碳-碳双键，一个碳-氧双键，为高级不饱和脂肪酸。其广泛分布于动物界，少量存在于某个种的甘油酯中，也能在甘油磷脂类中找到。其在人体内可由亚油酸合成。
本发明人惊讶地发现，当将母乳低聚糖(HMO)(其优选为选自2’-岩藻糖基乳糖(2’-FL)、3’-岩藻糖基乳糖(3’-FL)、乳糖-N-岩藻五糖I(LNFP I)、乳糖-N-二岩藻六糖I(LNDFH I)、乳糖-N-二岩藻六糖II(LNDFH II)中的一种或多种的中性岩藻糖基化的母乳低聚糖，优选2’-岩藻糖基乳糖(2’-FL))与花生四烯酸(ARA)组合使用时，它们能够协同地促进骨骼发育，特别是可以协同改善骨密度、血液中钙和/或磷的吸收、骨小梁相对体积、骨小梁厚度、骨小梁分离度、血清中碱性磷酸酶ALP含量等与骨骼发育相关的指标的至少一种，同时还改善了所列其余指标的一种或多种、甚至全部。
在一种实施方式中，所述营养组合物由如下组成：
-母乳低聚糖(HMO)，优选中性岩藻糖基化的母乳低聚糖(HMO)，其优选地选自2’-岩藻糖基乳糖(2’-FL)、3’-岩藻糖基乳糖(3’-FL)、乳糖-N-岩藻五糖I(LNFP I)、乳糖-N-二岩藻六糖I(LNDFH I)、乳糖-N-二岩藻六糖II(LNDFH II)中的一种或多种，优选2’-岩藻糖基乳糖(2’-FL)；和
-花生四烯酸。
在一种实施方式，所述母乳低聚糖(HMO)为中性岩藻糖基化的母乳低聚糖(HMO)，其优选地选自2’-岩藻糖基乳糖(2’-FL)、3’-岩藻糖基乳糖(3’-FL)、乳糖-N-岩藻五糖I(LNFP I)、乳糖-N-二岩藻六糖I(LNDFH I)、乳糖-N-二岩藻六糖II(LNDFH II)中的一种或多种，优选2’-岩藻糖基乳糖(2’-FL)。
在一种实施方式中，所述母乳低聚糖为2’-岩藻糖基乳糖(2’-FL)。
在一种实施方式中，所述母乳低聚糖(HMO)(例如选自2’-岩藻糖基乳糖(2’-FL)、3’-岩藻糖基乳糖(3’-FL)、乳糖-N-岩藻五糖I(LNFP I)、乳糖-N-二岩藻六糖I(LNDFH I)、乳糖-N-二岩藻六糖II(LNDFH II)的中性岩藻糖基化的母乳低聚糖(HMO)，例如2’-岩藻糖基乳糖(2’-FL))可以如下来源形式提供：天然来源，和/或合成来源，和/或细菌发酵来源。例如，对于2’-岩藻糖基乳糖，各来源中2’-岩藻糖基乳糖含量通常可以为60-99.9％质量、或者任何其它含量。
在一种实施方式中，所述营养组合物中，相对于1质量份的花生四烯酸(ARA)，母乳低聚糖(例如选自2’-岩藻糖基乳糖(2’-FL)、3’-岩藻糖基乳糖(3’-FL)、乳糖-N-岩藻五糖I(LNFP I)、乳糖-N-二岩藻六糖I(LNDFH I)、乳糖-N-二岩藻六糖II(LNDFH II)的中性岩藻糖基化的母乳低聚糖(HMO)，例如2’-岩藻糖基乳糖(2’-FL)可以为0.01-10000、优选0.05-5000、优选0.1-3000、优选0.3-1000、优选2-500、优选3-200质量份，例如可以为0.01、0.02、0.03、0.04、0.05、0.06、0.07、0.08、0.09、0.10、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、1.0、1.1、1.2、1.3、1.4、1.5、1.6、1.7、1.8、1.9、2.0、2.1、2.2、2.3、2.4、2.5、2.6、2.7、2.8、2.9、3.0、3.1、3.2、3.3、3.4、3.5、3.6、3.7、3.8、3.9、4.0、4.1、4.2、4.3、4.4、4.5、4.6、4.7、4.8、4.9、5.0、5.1、5.2、5.3、5.4、5.5、5.6、5.7、5.8、5.9、6.0、6.1、6.2、6.3、6.4、6.5、6.6、6.7、6.8、6.9、7.0、7.1、7.2、7.3、7.4、7.5、7.6、7.7、7.8、7.9、8.0、8.1、8.2、8.3、8.4、8.5、8.6、8.7、8.8、8.9、9.0、9.1、9.2、9.3、9.4、9.5、9.6、9.7、9.8、9.9、10.0、11.0、12.0、13.0、14.0、15.0、16.0、17.0、18.0、19.0、20.0、21.0、22.0、23.0、24.0、25.0、26.0、27.0、28.0、29.0、30.0、31.0、32.0、33.0、34.0、35.0、36.0、37.0、38.0、39.0、40.0、41.0、42.0、43.0、44.0、45.0、46.0、47.0、48.0、49.0、50.0、51.0、52.0、53.0、54.0、55.0、56.0、57.0、58.0、59.0、60.0、61.0、62.0、63.0、64.0、65.0、66.0、67.0、68.0、69.0、70.0、71.0、72.0、73.0、74.0、75.0、76.0、77.0、78.0、79.0、80.0、81.0、82.0、83.0、84.0、85.0、86.0、87.0、88.0、89.0、90.0、91.0、92.0、93.0、94.0、95.0、96.0、97.0、98.0、99.0、100、110、120、130、140、150、160、170、180、190、200、210、220、230、240、250、260、270、280、290、300、310、320、 330、340、350、360、370、380、390、400、410、420、430、440、450、460、470、480、490、500、510、520、530、540、550、560、570、580、590、200、610、620、630、640、650、660、670、680、690、300、710、720、730、740、750、760、770、780、790、800、810、820、830、840、850、860、870、880、890、900、910、920、930、940、950、960、970、980、990、1000、1100、1200、1300、1400、1500、1600、1700、1800、1900、2000、2100、2200、2300、2400、2500、2600、2700、2800、2900、3000、3100、3200、3300、3400、3500、3600、3700、3800、3900、4000、4100、4200、4300、4400、4500、4600、4700、4800、4900、5000、5100、5200、5300、5400、5500、5600、5700、5800、5900、6000、6100、6200、6300、6400、6500、6600、6700、6800、6900、7000、7100、7200、7300、7400、7500、7600、7700、7800、7900、8000、8100、8200、8300、8400、8500、8600、8700、8800、8900、9000、9100、9200、9300、9400、9500、9600、9700、9800、9900、10000、或者由其任意两者限定的范围。
所述营养组合物可以用于促进人体或动物体(例如哺乳动物)的骨骼发育。当营养组合物中母乳低聚糖(例如选自2’-岩藻糖基乳糖(2’-FL)、3’-岩藻糖基乳糖(3’-FL)、乳糖-N-岩藻五糖I(LNFP I)、乳糖-N-二岩藻六糖I(LNDFH I)、乳糖-N-二岩藻六糖II(LNDFH II)的中性岩藻糖基化的母乳低聚糖(HMO)，例如2’-岩藻糖基乳糖(2’-FL))与花生四烯酸(ARA)的质量比在上述范围内时，能够更显著地促进骨骼发育(例如改善骨密度、血液中钙和/或磷的吸收、骨小梁相对体积、骨小梁厚度、骨小梁分离度、血清中碱性磷酸酶ALP含量等与骨骼发育相关的指标的一种或多种、甚至全部)，尤其是促进婴幼儿及儿童骨骼发育，并且组分之间在促进骨骼发育(例如在改善骨密度、血液中钙和/或磷的吸收、骨小梁相对体积、骨小梁厚度、骨小梁分离度、血清中碱性磷酸酶ALP含量等与骨骼发育相关的指标的至少一种)方面的协同作用更加显著。
食品
在另一方面中，本发明还涉及包含所述营养组合物的食品。
本发明的食品可以是粉末形式，也可以是液体形式。
本发明的食品可以是婴幼儿配方食品(例如婴儿配方食品、较大婴儿配 方食品、幼儿配方食品)例如婴幼儿配方奶粉(例如婴儿配方奶粉、幼儿配方奶粉)、婴儿辅食、营养或膳食补充剂、或孕妇调制奶粉。
在一种实施方式中，所述营养组合物的添加量使得，相对于所述食品的总质量，母乳低聚糖(例如选自2’-岩藻糖基乳糖(2’-FL)、3’-岩藻糖基乳糖(3’-FL)、乳糖-N-岩藻五糖I(LNFP I)、乳糖-N-二岩藻六糖I(LNDFH I)、乳糖-N-二岩藻六糖II(LNDFH II)的中性岩藻糖基化的母乳低聚糖(HMO)，例如2’-岩藻糖基乳糖(2’-FL))的质量含量为至少0.005％、优选至少0.01％、优选至少0.05％，且优选至多20.0％、优选至多10.0％。例如，相对于所述食品的总质量，母乳低聚糖(例如选自2’-岩藻糖基乳糖(2’-FL)、3’-岩藻糖基乳糖(3’-FL)、乳糖-N-岩藻五糖I(LNFP I)、乳糖-N-二岩藻六糖I(LNDFH I)、乳糖-N-二岩藻六糖II(LNDFH II)的中性岩藻糖基化的母乳低聚糖(HMO)，例如2’-岩藻糖基乳糖(2’-FL))的质量含量可以为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％、0.10％、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％、1.0％、1.1％、1.2％、1.3％、1.4％、1.5％、1.6％、1.7％、1.8％、1.9％、2.0％、2.1％、2.2％、2.3％、2.4％、2.5％、2.6％、2.7％、2.8％、2.9％、3.0％、3.1％、3.2％、3.3％、3.4％、3.5％、3.6％、3.7％、3.8％、3.9％、4.0％、4.1％、4.2％、4.3％、4.4％、4.5％、4.6％、4.7％、4.8％、4.9％、5.0％、5.1％、5.2％、5.3％、5.4％、5.5％、5.6％、5.7％、5.8％、5.9％、6.0％、6.1％、6.2％、6.3％、6.4％、6.5％、6.6％、6.7％、6.8％、6.9％、7.0％、7.1％、7.2％、7.3％、7.4％、7.5％、7.6％、7.7％、7.8％、7.9％、8.0％、8.1％、8.2％、8.3％、8.4％、8.5％、8.6％、8.7％、8.8％、8.9％、9.0％、9.1％、9.2％、9.3％、9.4％、9.5％、9.6％、9.7％、9.8％、9.9％、10.0％、11.1％、11.2％、11.3％、11.4％、11.5％、11.6％、11.7％、11.8％、11.9％、12.0％、12.1％、12.2％、12.3％、12.4％、12.5％、12.6％、12.7％、12.8％、12.9％、13.0％、13.1％、13.2％、13.3％、13.4％、13.5％、13.6％、13.7％、13.8％、13.9％、14.0％、14.1％、14.2％、14.3％、14.4％、14.5％、14.6％、14.7％、14.8％、14.9％、15.0％、15.1％、15.2％、15.3％、15.4％、15.5％、15.6％、15.7％、15.8％、15.9％、16.0％、16.1％、16.2％、16.3％、16.4％、16.5％、16.6％、16.7％、16.8％、16.9％、17.0％、17.1％、17.2％、17.3％、17.4％、 17.5％、17.6％、17.7％、17.8％、17.9％、18.0％、18.1％、18.2％、18.3％、18.4％、18.5％、18.6％、18.7％、18.8％、18.9％、19.0％、19.1％、19.2％、19.3％、19.4％、19.5％、19.6％、19.7％、19.8％、19.9％、20.0％、或者由其任意两者限定的范围。
在一种实施方式中，所述营养组合物的添加量使得，相对于所述食品的总质量，花生四烯酸的质量含量为至少0.0005％、优选至少0.001％、优选至少0.003％，且优选至多1.0％、优选至多0.5％。例如，相对于所述食品的总质量，花生四烯酸的质量含量可以为0.0005％、0.0006％、0.0007％、0.0008％、0.0009％、0.0010％、0.0015％、0.0020％、0.0025％、0.0030％、0.0035％、0.0040％、0.0045％、0.0050％、0.0055％、0.0060％、0.0065％、0.0070％、0.0075％、0.0080％、0.0085％、0.0090％、0.0095％、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％、0.10％、0.11％、0.12％、0.13％、0.14％、0.15％、0.16％、0.17％、0.18％、0.19％、0.20％、0.21％、0.22％、0.23％、0.24％、0.25％、0.26％、0.27％、0.28％、0.29％、0.30％、0.31％、0.32％、0.33％、0.34％、0.35％、0.36％、0.37％、0.38％、0.39％、0.40％、0.41％、0.42％、0.43％、0.44％、0.45％、0.46％、0.47％、0.48％、0.49％、0.50％、0.51％、0.52％、0.53％、0.54％、0.55％、0.56％、0.57％、0.58％、0.59％、0.60％、0.61％、0.62％、0.63％、0.64％、0.65％、0.66％、0.67％、0.68％、0.69％、0.70％、0.71％、0.72％、0.73％、0.74％、0.75％、0.76％、0.77％、0.78％、0.79％、0.80％、0.81％、0.82％、0.83％、0.84％、0.85％、0.86％、0.87％、0.88％、0.89％、0.90％、0.91％、0.92％、0.93％、0.94％、0.95％、0.96％、0.97％、0.98％、0.99％、1.0％、或者由其任意两者限定的范围。
当所述食品中母乳低聚糖(例如选自2’-岩藻糖基乳糖(2’-FL)、3’-岩藻糖基乳糖(3’-FL)、乳糖-N-岩藻五糖I(LNFP I)、乳糖-N-二岩藻六糖I(LNDFH I)、乳糖-N-二岩藻六糖II(LNDFH II)的中性岩藻糖基化的母乳低聚糖(HMO)，例如2’-岩藻糖基乳糖(2’-FL))和花生四烯酸的质量含量在上述范围内时，可以更显著地促进(例如人体或动物体)骨骼发育(例如改善骨密度、血液中钙和/或磷的吸收、骨小梁相对体积、骨小梁厚度、骨小梁分离度、血清中碱性磷酸酶ALP含量等与骨骼发育相关的指标的一种或多种、甚至全部)，尤其是促进婴幼儿及儿童骨骼发育，并且组分之间在促进骨骼发育(例如在改善骨 密度、血液中钙和/或磷的吸收、骨小梁相对体积、骨小梁厚度、骨小梁分离度、血清中碱性磷酸酶ALP含量等与骨骼发育相关的指标的至少一种)方面的协同作用更加显著；并且同时还能够平衡(例如人体或动物所需要的)各方面营养。
在一种实施方式中，所述营养组合物的添加量使得，所述食品中母乳低聚糖(例如选自2’-岩藻糖基乳糖(2’-FL)、3’-岩藻糖基乳糖(3’-FL)、乳糖-N-岩藻五糖I(LNFP I)、乳糖-N-二岩藻六糖I(LNDFH I)、乳糖-N-二岩藻六糖II(LNDFH II)的中性岩藻糖基化的母乳低聚糖(HMO)，例如2’-岩藻糖基乳糖(2’-FL))和花生四烯酸的质量比为2-300∶1、优选3-200∶1、或者上文中(在营养组合物部分中)提及的在此范围内的任何其它值或范围，并且相对于所述食品的总质量，母乳低聚糖(例如选自2’-岩藻糖基乳糖(2’-FL)、3’-岩藻糖基乳糖(3’-FL)、乳糖-N-岩藻五糖I(LNFP I)、乳糖-N-二岩藻六糖I(LNDFH I)、乳糖-N-二岩藻六糖II(LNDFH II)的中性岩藻糖基化的母乳低聚糖(HMO)，例如2’-岩藻糖基乳糖(2’-FL))的量为至少0.05％、优选至少0.06％，且优选为至多10％、优选至多6％、优选至多3％，或者上文中提及的在此范围内的任何其它值或范围。在一种进一步优选的实施方式中，所述营养组合物的添加量使得，相对于所述食品的总质量，花生四烯酸的量为至少0.0025％、优选至少0.0030％、优选至少0.0035％，且优选至多1％、优选至多0.6％、优选至多0.3％，或者上文中提及的在此范围内的任何其它值或范围。当母乳低聚糖例如2’-岩藻糖基乳糖(2’-FL))与花生四烯酸的比例以及用量在上述范围内或者优选范围内时，这两种组分在促进骨骼健康，尤其是增加骨密度方面的协同作用更为显著。
除了以上对于所述营养组合物中所描述的组分之外，所述食品还可以包含其它成分，例如蛋白质/氨基酸、碳水化合物、脂肪、维生素、矿物质等在配方食品例如婴幼儿配方食品如奶粉中经常含有的成分。
用途
在另一方面中，本发明涉及上述营养组合物或者上述食品在促进骨骼发育，尤其是促进婴幼儿及儿童骨骼发育中的非治疗目的的用途。
在一种实施方式中，所述促进骨骼发育包括改善如下(与骨骼发育有关的指标)的至少一种：骨密度、血液中钙和/或磷的吸收、骨小梁相对体积、 骨小梁厚度、骨小梁分离度、和血清中碱性磷酸酶ALP含量。
在一种实施方式中，所述促进骨骼发育包括：促进人体骨骼发育、尤其是促进婴幼儿及儿童骨骼发育；和/或促进动物体、尤其是哺乳动物骨骼发育。
实施例
为了使本发明的目的、技术方案及优点更加清楚明白，以下结合实施例，对本发明进行进一步详细说明。应当理解，此处所描述的具体实施例仅用以解释本发明，并不用于限定本发明。除非特别说明，本发明采用的试剂、方法和设备为本技术领域常规的试剂、方法和设备。
1.材料与方法
1.1主要试剂
1％戊巴比妥钠：德国Merck公司
碱性磷酸酶试剂盒(211026101)、钙/磷试剂盒(201102301/210305101)：美康生物科技股份有限公司；
花生四烯酸(ARA)：嘉必优生物技术(武汉)有限公司，CAB-AP-FP2-1-21052101，产品批号APKD14，ARA含量21.2％质量
2′-岩藻糖基乳糖：GlyCareTM 2FL 9000，纯度96.0％质量
基础饲料：大小鼠繁殖饲料，上海普路腾生物科技有限公司，斯莱康(SLACOM)，产品标准编号Q31/0117000777C001-2017，产品编号P1101F-25，生产批号：P110F-25-20220107001，实验动物饲料物营养标准GB14924.3-2010，饲料卫生标准GB13078-2017，实验动物饲料卫生标准GB14924.2-2001，其中以质量计，水分≤10％，粗蛋白质≥20.5％，粗脂肪≥4％；粗纤维≤5％，粗灰分≤8％，钙1.0-1.8％，总磷0.6-1.2％；赖氨酸≥1.32％，蛋氨酸+胱氨酸≥0.78％，氯化钠0.4％
1.2仪器设备
万分之一电子天平BS110：北京赛多利斯仪器系统有限公司
电热恒温水浴锅DZW：天津莱斯特仪器有限公司
电冰箱BCD-160TMPQ：青岛海尔股份有限公司
涡旋振荡器VS-10M：惟沃索科技术北京有限公司
离心机TG16K-II：上海化工机械公司
超低温冰箱88300V：美国ThermoFisher公司)
小动物活体断层扫描成像系统U-CT-XUHR：荷兰Milabs
全自动生化分析仪HITACHI 7020：日本日立公司
1.3实验动物
购入健康状况稳定的幼年(4周龄)雄性C56BL/6小鼠，SPF级，约228只。饲养环境：室温20-25℃，每12小时光照明暗交替，相对湿度约50％，饲料、饮水等均统一匹配，保持室内环境良好通风，每天清洁，维持笼内良好卫生环境；动物福利：在进行实验的全部处理过程中，对小鼠进行合理手段，符合实验动物伦理委员会的相关规定，具体按IAC类及其他相关标准操作规程(SOP)进行；处死方法：实验结束及剔除的小鼠均先进行麻醉腹动脉放血处死，然后将尸体存放专用冰柜容器，最后无害化统一处理。
1.4实验分组
各实施例中所使用的如表1所示，其中ARA和2’-FL的量均指的是该具体活性物的量。
表1：动物实验剂量
1.5指标检测
1.5.1骨密度及骨骼相关指标检测
采用1％戊巴比妥钠麻醉小鼠，将其固定于小动物活体断层扫描成像仪上，分辨率为20μm，扫描结束后进行图像重建，采用Inveon Research Workplace 2.2软件分析各组小鼠骨密度、骨小梁相对体积(Tb.BV/TV)、骨小梁相对数目(Tb.N)、骨小梁分离度(Tb.Sp)等。
1.5.2小鼠血钙、磷和碱性磷酸酶的测定
将小鼠血样进行转速为3000r/min离心，离心15min后，分管-80℃保存，待用。取制备后血清上层液，用相应试剂盒进行相应的钙、磷和碱性磷酸酶(ALP)含量指标检测，操作步骤严格按照试剂盒说明书进行。
1.6统计学分析
实验数据以平均数±标准差(mean±SD)的方式来表示，每个实验至少独立重复三次，采用GraphPad Prism 8.00、Excel 2018及R语言绘制图表，应用SPSS 16.0软件对实验数据进行统计分析，运用单因素方差分析(Duncan’s multiple range test)。P＜0.05代表差异显著。
2.实验结果
2.1各受试物对小鼠骨密度的影响
为评价受试物单独或混合处理对小鼠骨骼健康的影响，测定了各组小鼠骨密度情况，如表2所示。
表2：各受试物对小鼠骨密度的影响(mean±SD，n＝3)


注：*与空白对照组比较P＜0.05，**与空白对照组比较P＜0.01，***与空
白对照组比较P＜0.001。
样品处理结果显示，与空白对照组相比，各实施例均使骨密度显著增加。骨密度是衡量骨骼健康的重要指标，说明各实施例均能够促进骨骼发育和健康。
本发明人还发现，ARA与2’-FL在组合使用时存在协同效应，能够协同地促进骨骼发育和健康，例如增加骨密度。
例如，就使用的组分以及用量而言，实验例2相当于对比例2和6的组合，相对于空白对照组而言，实施例2、对比例2、对比例6分别使得骨密度增加了88.57、50.47、18.22，实施例2中骨密度的增量(88.57)大于对比例2和6各自的增量之和(68.69)。
实验例3相当于对比例3和5的组合，相对于空白对照组而言，实施例3、对比例3、对比例5分别使得骨密度增加了89.57、60.56、18.12，实施例3中骨密度的增量(89.57)大于对比例3和5各自的增量之和(78.68)。
实验例7相当于对比例3和6的组合，相对于空白对照组而言，实施例7、对比例3、对比例6分别使得骨密度增加了90.2、60.56、18.22，实施例7中骨密度的增量(90.2)大于对比例3和6各自的增量之和(78.78)。
2.2各受试物对小鼠Bv/Tv骨小梁相对体积的影响
为评价受试物单独或混合处理对小鼠骨骼的影响，测定了各组小鼠骨小梁的情况，如表3、4、5所示。
2.2.1各受试物对小鼠Bv/Tv骨小梁相对体积的影响
表3：各受试物对小鼠Bv/Tv骨小梁相对体积的影响(mean±SD，n＝3)


注：*与空白对照组比较P＜0.05，**与空白对照组比较P＜0.01。
骨小梁相对体积(Bv/Tv)，该比值能够反应不同样本骨小梁骨量的多少，该值增高说明骨合成代谢大于分解代谢，骨量增加，反之亦然，从而能够间接反映骨代谢状况。
样品处理结果显示，与空白对照组相比，各实施例均能够显著增加骨小梁相对体积，从而表明各实施例均能够促进骨骼发育和健康。
本发明人还发现，ARA与2’-FL在组合使用时存在协同效应，能够协同地促进骨骼发育和健康，例如增加骨小梁相对体积。
例如，就使用的组分以及用量而言，实验例4相当于对比例1和5的组合，相对于空白对照组而言，实施例4、对比例1、对比例5分别使得骨小梁相对体积增加了0.026、0.009、0.016，实施例4中骨小梁相对体积的增量(0.026)大于对比例1和5各自的增量之和(0.025)。
实验例5相当于对比例2和4的组合，相对于空白对照组而言，实施例5、对比例2、对比例4分别使得骨小梁相对体积增加了0.027、0.009、0.006，实施例5骨小梁相对体积的增量(0.027)大于对比例2和4自的增量之和(0.015)。
2.2.2各受试物对小鼠Tb/Th骨小梁厚度、Tb/Sp骨小梁分离度的影响
表4：各受试物对小鼠Tb/Th骨小梁厚度的影响(mean±SD，n＝3)


注：*与空白对照组比较P＜0.05。
表5：各受试物对小鼠Tb/Sp骨小梁分离度的影响(mean±SD，n＝3)

注：*与空白对照组比较P＜0.05，**与空白对照组比较P＜0.01，***与空
白对照组比较P＜0.001。
骨小梁厚度(trabecular thickness，Tb.Th)和骨小梁分离度(trabecular  separation，Tb.Sp)是评价骨小梁空间形态结构的主要指标。骨分解代谢大于骨合成代谢时情况下，如发生骨质疏松时，Tb/Th数值减少；Tb/Sp数值增加。
样品处理结果显示，与空白对照组相比，各实施例均能显著增加骨小梁厚度，并且显著降低骨小梁分离度，从而表明各实施例均能够显著促进骨骼发育和健康。
本发明人还发现，ARA与2’-FL在组合使用时存在协同效应，能够协同地促进骨骼发育和健康，例如增加骨小梁厚度。
例如，就使用的组分以及用量而言，实验例1相当于对比例1和6的组合，相对于空白对照组而言，实施例1、对比例1和对比例6分别使得骨小梁厚度增加了0.0026、0.0005、0.0005，实施例1中骨小梁厚度的增量(0.0026)大于对比例1和6各自的增量之和(0.001)。
实验例4相当于对比例1和5的组合，相对于空白对照组而言，实施例4、对比例1和对比例5分别使得骨小梁厚度增加了0.0012、0.0005、0.0002，实施例4中骨小梁厚度的增量(0.0012)大于对比例1和5各自的增量之和(0.0007)。
实验例6相当于对比例3和4的组合，相对于空白对照组而言，实施例6、对比例3和对比例4分别使得骨小梁厚度增加了0.0033、0.0015、0.001，实施例6中骨小梁厚度的增量(0.0033)大于对比例3和4各自的增量之和(0.0025)。
实验例7相当于对比例3和6的组合，相对于空白对照组而言，实施例7、对比例3和对比例6分别使得骨小梁厚度增加了0.0033、0.0015、0.0005，实施例7中骨小梁厚度的增量(0.0033)大于对比例3和6各自的增量之和(0.002)。
2.2各受试物对大鼠血液中碱性磷酸酶的影响
为评价受试物单独或混合处理对小鼠骨代谢的影响，测定了各组小鼠血清中碱性磷酸酶的情况，如表6所示。
表6：各受试物对小鼠血清中碱性磷酸酶的影响(mean±SD，n＝8)


注：*与空白对照组比较P＜0.05，**与空白对照组比较P＜0.01，***与空
白对照组比较P＜0.001。
ALP主要由成骨细胞和肝脏合成分泌，是反映骨代谢的重要指标。在成骨活跃时是由成骨细胞分泌。在血清中50％的ALP是由成骨分泌产生，因此，在一定程度上，血清ALP水平反映骨代谢的变化情况。相关研究结果显示，在机体内出现骨质快速流失或是存在骨折风险时，机体内血清ALP水平明显升高，分析其原因可能是骨吸收的加剧，导致代偿性骨形成以及骨转换增强。
样品处理结果显示，与空白对照组相比，各实施例均显著减少了碱性磷酸酶的含量，说明各实施例均能够降低碱性磷酸酶活性，改善骨代谢，从而促进骨骼发育和健康。
本发明人还发现，ARA与2’-FL在组合使用时存在协同效应，能够协同地促进骨骼发育和健康，例如协同地减少血清中碱性磷酸酶含量，改善骨代谢。
例如，就使用的组分以及用量而言，实验例3相当于对比例3和5的组合，相对于空白对照组而言，实施例3、对比例3、对比例5分别使得碱性磷酸酶降低了12.90、10.90、1.47，实施例3碱性磷酸酶减量(12.90)大于对比例3和5各自的减量之和(12.37)。
实施例4相当于对比例1和5的组合，相对于空白对照组而言，实施例4、对比例1、对比例5分别使得碱性磷酸酶降低了6.85、3.30、1.47，实施例4中碱性磷酸酶减量(6.85)大于对比例3和6各自的减量之和(4.77)。
实验例6相当于对比例3和4的组合，相对于空白对照组而言，实施例6、对比例3、对比例4分别使得碱性磷酸酶降低了18.20、10.90、4.83，实施例7中碱性磷酸酶减量(18.20)大于对比例3和6各自的减量之和(15.73)。
实验例7相当于对比例3和6的组合，相对于空白对照组而言，实施例7、 对比例3、对比例6分别使得碱性磷酸酶降低了20.59、10.90、7.73，实施例7中碱性磷酸酶减量(20.59)大于对比例3和6各自的减量之和(18.63)。
2.4各受试物对大鼠血清中Ca、P含量的影响
为评价受试物单独或混合处理对小鼠骨骼健康的影响，测定了各组小鼠血清中Ca、P的含量，如表7、8所示。
表7：各受试物对小鼠血清中Ca含量的影响(mean±SD，n＝8)
注：*与空白对照组比较P＜0.05，**与空白对照组比较P＜0.01，***与空白对照组比较P＜0.001。
表8：各受试物对小鼠血清中P含量的影响(mean±SD，n＝8)


注：*与空白对照组比较P＜0.05，**与空白对照组比较P＜0.01，***与空
白对照组比较P＜0.001。
钙和磷是构成骨骼的主要元素，在骨骼的建立中相互协调。
样品处理结果显示，与空白对照组相比，各实施例均显著增加了血清中Ca、P的含量，说明两种组分在骨骼建立中可以相互协调，增加Ca、P的吸收，从而促进骨骼发育和健康。
本发明人还发现，ARA与2’-FL在组合使用时存在协同效应，能够协同地促进骨骼发育和健康，例如能够协同地增加血清中Ca、P的含量。
例如，就使用的组分以及用量而言，实施例3相当于对比例3和5的组合，相对于空白对照组而言，实施例3、对比例3和对比例5分别使得血清中Ca的含量增加了0.22、0.13、0.07，实施例3中Ca的增量(0.22)大于对比例3和5各自的增量之和(0.20)。
实施例4相当于对比例1和5的组合，相对于空白对照组而言，实施例4、对比例1和对比例5分别使得血清中Ca的含量增加了0.13、0.05、0.07，实施例4中Ca的增量(0.13)大于对比例1和5各自的增量之和(0.12)。
由表2-8可见，当将母乳低聚糖例如2’-FL和ARA两者组合使用时，能够显著地改善骨密度、血液中钙和磷的吸收、骨小梁相对体积、骨小梁厚度、骨小梁分离度、血清中碱性磷酸酶ALP含量等与骨骼发育相关的指标，并且同时能够协同地改善骨密度、血液中钙和/或磷的吸收、骨小梁相对体积、骨小梁厚度、骨小梁分离度、碱性磷酸酶ALP等与骨骼发育相关的指标的至少一种，从而能够促进骨骼发育和健康。
本发明提供了母乳低聚糖例如2’-岩藻糖基乳糖(2’-FL)、二十碳四烯酸 (ARA)组合物在骨骼发育和健康，例如在改善骨密度、血液中钙和/或磷的吸收、骨小梁相对体积、骨小梁厚度、骨小梁分离度、血清中碱性磷酸酶ALP含量等与骨骼发育相关的指标的研究，为未来功能性食品的开发提供了新思路。母乳低聚糖例如2’-岩藻糖基乳糖(2’-FL)、二十碳四烯酸(ARA)在机体促进骨骼发育方面的前景广阔，研究发现在改善骨骼发育和健康方面具有较好的协同效应。
应用实施例
以下应用例中的″份″均为质量份数，成分的％含量均为质量％含量。
另外，在以下各应用例中，除非另有说明，否则所使用的以下原料来源如下。
全脂乳粉：黑龙江飞鹤乳业有限公司
生牛乳：黑龙江飞鹤乳业有限公司
脱脂乳粉：爱尔兰Kerry
花生四烯酸(ARA)：嘉必优生物技术(武汉)有限公司
二十二碳六烯酸(DHA)：嘉必优生物技术(武汉)有限公司
2′-岩藻糖基乳糖(2′-岩藻糖基乳糖96.0％)：GlyCareTM 2FL 9000
脱盐乳清粉：法国Euroserum(红鸟)
乳糖：美国Hilmar
低聚半乳糖：保龄宝生物股份有限公司
混合植物油：嘉吉粮油(南通)有限公司
复配维生素：帝斯曼维生素(上海)有限公司
复配矿物质：帝斯曼维生素(上海)有限公司
固体玉米糖浆：保龄宝生物股份有限公司
碳酸钙：南通励成生物工程有限公司
磷酸氢钙：郑州瑞普生物工程有限公司
柠檬酸钠：日照金禾生化集团股份有限公司
氯化钾：郑州瑞普生物工程有限公司
复配氯化花生四烯酸：北京金康普食品科技有限公司
复配核苷酸：大连珍奥生物工程股份有限公司
低聚半乳糖：保龄宝生物股份有限公司
低聚异麦芽糖：保龄宝生物股份有限公司
单双甘油脂肪酸酯：丹尼斯克(中国)有限公司
应用例1
含有2’-岩藻糖基乳糖(2’-FL)、二十碳四烯酸(ARA)的婴儿配方奶粉，每1000份婴儿配方奶粉由如下质量份的组分制得：
本发明的奶粉所用的原料有：全脂奶粉180份(每份含二十碳四烯酸0.08％)、2’-岩藻糖基乳糖8.3份(每份中2’-岩藻糖基乳糖96.0％)、二十碳四烯酸油脂粉15份(每份中二十碳四烯酸10％)、脱盐乳清粉400份、乳糖119.95份、低聚半乳糖50份，混合植物油190份、二十二碳六烯酸油脂粉15份、柠檬酸钠3份、氯化钾3份、碳酸钙3份、磷酸氢钙4份、复配维生素3份、复配矿物质2份、复配营养素1份、复配氯化花生四烯酸2.1份、复配核苷酸0.65份；将上述原料混合均匀后，经巴氏杀菌、均质、蒸发浓缩和喷雾干燥成粉状半成品，将混合均匀后的奶粉充氮包装即得终产品。产品中含量2′-岩藻糖基乳糖0.8％，二十碳四烯酸(ARA)0.16％。
应用例2
含有2’-岩藻糖基乳糖(2’-FL)、二十碳四烯酸(ARA)的幼儿配方奶粉，每1000份幼儿配方奶粉由如下质量份的组分制得：
本发明的奶粉所用的原料有：生牛乳以固形物计231.8份(每份含二十碳四烯酸0.08％)、2’-岩藻糖基乳糖0.83份(每份中2’-岩藻糖基乳糖96.0％)、二十碳四烯酸油脂粉2份(每份中二十碳四烯酸10％)、脱盐乳清粉275份、乳糖166.12份、脱脂乳粉125份、低聚半乳糖50份，混合植物油130份、二十二碳六烯酸油脂粉4份、柠檬酸钠1份、氯化钾1份、碳酸钙3.5份、磷酸氢钙1份、复配维生素3份、复配矿物质2份、复配营养素1份、复配氯化花生四烯酸2.1份、复配核苷酸0.65份；将上述原料混合均匀后，经巴氏杀菌、均质、蒸发浓缩和喷雾干燥成粉状半成品，将混合均匀后的奶粉充氮包装即得终产品。产品中含量2’-岩藻糖基乳糖0.08％，二十碳四烯酸(ARA)0.04％。
应用例3
含有2’-岩藻糖基乳糖(2’-FL)、二十碳四烯酸(ARA)的幼儿配方奶粉， 每1000份幼儿配方奶粉由如下质量份的组分制得：
本发明的奶粉所用的原料有：生牛乳以固形物计231.8份(每份含二十碳四烯酸0.08％)、2’-岩藻糖基乳糖8.3份(每份中2’-岩藻糖基乳糖96.0％)、二十碳四烯酸油脂粉2份(每份中二十碳四烯酸10％)、脱盐乳清粉275份、乳糖158.65份、脱脂乳粉125份、低聚半乳糖50份，混合植物油130份、二十二碳六烯酸油脂粉4份、柠檬酸钠1份、氯化钾1份、碳酸钙3.5份、磷酸氢钙1份、复配维生素3份、复配矿物质2份、复配营养素1份、复配氯化花生四烯酸2.1份、复配核苷酸0.65份；将上述原料混合均匀后，经巴氏杀菌、均质、蒸发浓缩和喷雾干燥成粉状半成品，将混合均匀后的奶粉充氮包装即得终产品。产品中含量2’-岩藻糖基乳糖0.8％，二十碳四烯酸(ARA)0.04％。
应用例4
含有2’-岩藻糖基乳糖(2’-FL)、二十碳四烯酸(ARA)的调制乳粉，适用于孕妇食用，每1000份调制奶粉由如下质量份的组分制得：
本发明的奶粉所用的原料有：脱脂奶粉590份、2’-岩藻糖基乳糖0.83份(每份中2’-岩藻糖基乳糖96.0％)、二十碳四烯酸油脂粉0.8份(每份中二十碳四烯酸10％)、植物油96份、乳糖74.37份、固体玉米糖浆195份、低聚异麦芽糖40份、复配维生素2份、复配矿物质1份；将上述原料混合均匀后，经巴氏杀菌、均质、蒸发浓缩和喷雾干燥成粉状半成品，将混合均匀后的奶粉充氮包装即得终产品。产品中2’-岩藻糖基乳糖含量0.08％，二十碳四烯酸0.008％。
应用例5
含有2’-岩藻糖基乳糖(2’-FL)、二十碳四烯酸(ARA)的调制乳粉，适用于中老年食用，每1000份调制乳粉由如下质量份的组分制得：
本发明的奶粉所用的原料有：全脂乳粉436份(每份含二十碳四烯酸0.08％)、2’-岩藻糖基乳糖86.34份(每份中2’-岩藻糖基乳糖96.0％)、二十碳四烯酸油脂粉17份(每份中二十碳四烯酸10％)、脱脂乳粉250份、固体玉米糖浆172.66份、低聚异麦芽糖35份、复配维生素2份、复配矿物质1份；将上述原料混合均匀后，经巴氏杀菌、均质、蒸发浓缩和喷雾干燥成粉状半 成品，将混合均匀后的奶粉充氮包装即得终产品。产品中2’-岩藻糖基乳糖含量8.3％，二十碳四烯酸0.2％。
应用例6
含有2’-岩藻糖基乳糖(2’-FL)、二十碳四烯酸(ARA)的调制乳，每1000份调制乳由如下质量份的组分制得：
本发明的调制乳，生牛乳903.86份(每份含二十碳四烯酸0.01％)、2’-岩藻糖基乳糖83.34份(每份中2’-岩藻糖基乳糖96.0％)、二十碳四烯酸油脂粉3份(每份中ARA 10％)、低聚果糖9.3份、单双甘油脂肪酸酯0.5份；将上述原料混合、均质、UHT杀菌、均质，无菌灌装即得终产品。产品中2’-岩藻糖基乳糖含量8％，二十碳四烯酸(ARA)0.04％。
以上所述的仅是本发明的示例性实施方式。在此应当指出，对于本领域的普通技术人员来说，在不脱离本发明创造构思的前提下，还可以对本发明做出改进，但这些均属于本发明的保护范围。

Claims (10)

  1. 一种营养组合物，其包括如下或者由如下组成：
    -母乳低聚糖，优选中性岩藻糖基化的母乳低聚糖，其优选地选自2’-岩藻糖基乳糖、3’-岩藻糖基乳糖、乳糖-N-岩藻五糖I、乳糖-N-二岩藻六糖I、乳糖-N-二岩藻六糖II中的一种或多种，优选2’-岩藻糖基乳糖；和
    -花生四烯酸。
  2. 如权利要求1所述的营养组合物，其中母乳低聚糖以天然来源，和/或合成来源，和/或细菌发酵来源的形式提供。
  3. 如权利要求1-2任一项所述的营养组合物，其中：
    相对于1质量份的花生四烯酸，母乳低聚糖的量为0.01-10000、优选0.05-5000、优选0.1-3000、优选0.3-1000、优选2-500、优选3-200质量份。
  4. 食品，其包含如权利要求1-3任一项所述的营养组合物。
  5. 如权利要求4所述的食品，其中所述食品为粉末或者液体形式。
  6. 如权利要求4-5任一项所述的食品，其为婴幼儿配方食品例如婴儿配方食品、较大婴儿配方食品、幼儿配方食品，例如婴幼儿配方奶粉，例如婴儿配方奶粉、幼儿配方奶粉；婴儿辅食；营养或膳食补充剂；或孕妇调制奶粉。
  7. 如权利要求4-6任一项所述的食品，其中所述营养组合物的添加量使得，相对于所述食品的总质量：
    母乳低聚糖的质量含量为至少0.005％、优选至少0.01％、优选至少0.05％，且优选至多20.0％、优选至多10.0％，和
    花生四烯酸的质量含量为至少0.0005％、优选至少0.001％、优选至少0.003％，且优选至多1.0％、优选至多0.5％。
  8. 如权利要求4-7任一项所述的食品，其中所述营养组合物的添加量使得，相对于所述食品的总质量：
    母乳低聚糖的质量含量为至少0.05％、优选至少0.06％，且优选为至多10％、优选至多6％、优选至多3％，和
    花生四烯酸的质量含量为至少0.0025％、优选至少0.0030％，且优选至多1％、优选至多0.6％、优选至多0.3％；
    其中母乳低聚糖和花生四烯酸的质量比为2-300∶1、优选3-200∶1。
  9. 如权利要求1-3任一项所述的营养组合物或者如权利要求4-8任一项所述的食品在促进骨骼发育，尤其是促进婴幼儿及儿童骨骼发育中的非治疗目的的用途。
  10. 如权利要求9所述的用途，其中所述促进骨骼发育包括改善如下的至少一种：骨密度、血液中钙和/或磷的吸收、骨小梁相对体积、骨小梁相对数目、骨小梁分离度、和血清中碱性磷酸酶ALP含量。
PCT/CN2023/079303 2022-06-15 2023-03-02 营养组合物、包含其的食品以及该营养组合物的用途 WO2023241110A1 (zh)

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