Nutritional composition with improved segregation resistance

Abstract

The present invention relates to a powdered nutritional composition comprising (i) milk formula particles comprising lipids, proteins, digestible carbohydrates, and (ii) human milk oligosaccharide (HMO) particles wherein the nutritional composition is selected from the group consisting of infant formula, second stage formula, and growing milk wherein the nutritional composition is not human milk, and wherein the nutritional composition is a non-dairy product. And wherein the lipid in the milk formula granules is in the form of lipid globules, and a. The lipid globules have a mode diameter of at least 1 [mu] m on a volume basis, and / or b. At least 40% by volume of the lipid globules have a diameter of 2 to 12 [mu] m, and wherein the HMO granules comprise at least 2'fucosyllactose (2 'FL). The invention also relates to a method for preparing the composition and to the use thereof.

Description

Technical Field

[0001] The present invention relates to powdered nutritional compositions having improved resistance to segregation and comprising milk formula particles comprising lipids, proteins, digestible carbohydrates and human milk oligosaccharide (HMO) particles. The nutritional compositions are particularly infant formulas, second stage formulas or growing-up milks comprising lipid globules having a volume-weighted mode diameter of at least 1.0 μm, preferably at least 40% by volume of which have a diameter of 2 to 12 μm. Background Art

[0002] Infant formula or second formula is often used when breastfeeding is inadequate or unsuccessful due to medical reasons or because of a choice not to breastfeed. Commercial infant formula is often used to provide a supplemental or sole source of nutrition in the early stages of life. These formulas contain a range of nutrients to meet the nutritional needs of growing infants and typically include fat, carbohydrates, protein, vitamins, minerals and other nutrients that contribute to optimal infant growth and development.

[0003] Nutritional compositions for infants and young children are typically sold as powders to be reconstituted with water, or in some cases as ready-to-drink or concentrated liquid compositions. These compositions are intended to cover most or all of the nutritional requirements of an infant or young child.

[0004] Human milk lipids have a unique physical structure consisting of large lipid globules with an average mode diameter of approximately 4 μm, surrounded by a triglyceride core enclosed by a three-layer membrane: the milk fat globule membrane (MFGM). Due to industrial processing procedures to achieve a stable and reproducible end product, the lipid droplets in standard infant formulas are approximately 0.3 to 0.5 μm in diameter and are not surrounded by MFGM, but primarily by proteins such as casein. Standard commercially available formulas also mostly contain vegetable oils and have small lipid droplets with proteins attached to their surface. WO 2021008982 discloses a composition comprising lipids, proteins, and digestible carbohydrates for inducing satiety; wherein the lipids comprise: i) 30% to 90% by weight of vegetable fat, and ii) 10% to 70% by weight of mammalian milk fat, wherein all weight % are based on the total lipid content of the composition, characterized in that the lipids are present in the form of lipid globules, wherein the volume % of lipid globules with a diameter below 2 μm is greater than 60%, preferably greater than 70%, more preferably greater than 80%, and most preferably greater than 90%. The volume percentage of lipid globules with a diameter below 1 μm in the composition is 80%, and the volume % of lipid globules with a diameter below 2 μm is 92%. Based on volume, the mode diameter of the tested products is 0.46 μm. WO '982 discloses that the composition may further comprise one or more human milk oligosaccharides (HMOs), most preferably 2'FL. In addition, the lipid globules may comprise a coating comprising phospholipids (at least 0.5% by weight, such as phospholipids derived from MFGM).

[0005] Human milk is known to contain large amounts of indigestible human milk oligosaccharides, which represent the third largest solid component of breast milk and act as prebiotics. For example, various infant formulas supplemented with prebiotics, such as mixtures of fructooligosaccharides (FOS) and galacto-oligosaccharides (GOS), are commercially available. However, there is ongoing focus on adding human milk oligosaccharides (HMOs) to infant formula to provide a nutritional composition more similar to human breast milk and the associated health benefits.

[0006] It has been found that, as in most commercially available infant milk formulas (where the majority of fat droplets have a diameter below 1 μm), in nutritional compositions containing fat droplets with a low volume-weighted mode diameter (e.g., in WO '982 above), undesirable HMO segregation occurs. Powder segregation is an undesirable phenomenon because it is crucial for infant formula that each range of powders provide the same amount of nutrients. There should be no difference between the powder at the top and the powder at the bottom of the package.

[0007] Powder segregation can be caused by differences in the size, shape, or density of the powder particles. Particle size is probably the most important contributing factor to segregation.

[0008] Small particles may migrate downward by mass, falling into the spaces between larger particles in the powdered formula. Simultaneously, larger particles migrate upward in the so-called "Brazil nut effect," as voids form and are then filled by smaller particles, forcing the larger particles upward. This type of segregation, known as percolation, typically occurs after the powder is packaged, for example, during transportation of the packaged product from the factory to the consumer's home.

[0009] Infant formulas with lipid globules that are more similar to those in human milk have been described. In WO2011115476, WO 201027258 and WO 2012173467, there are disclosed the use of specially designed lipid components for early life diets to improve the development of a healthy body composition (particularly to prevent obesity later in life) and weight development more similar to that of breastfed infants, the lipid components having an optimal fatty acid composition, an increased proportion of palmitic acid residues at the sn-2 position, and being present as lipid globules of a specific size and / or coating.

[0010] These disclosures do not describe the effect of HMOs on the segregation behavior of these formulations when blended into them, especially when compared to formulations without these large fat droplets. While WO 2015067325 discloses that adding micronized lactose or another micronized carbohydrate to nutritional compositions with large fat droplets improves the flow of such products, WO '325 does not mention segregation properties. Regardless, HMOs and micronized lactose have significantly different properties in terms of physical parameters, as HMOs do not have the same micronized particle size and, in contrast to lactose, are indigestible to humans from a functional perspective.

[0011] The present invention provides infant formulas having lipid globules with an architecture more similar to that of lipid globules in human milk, the infant formulas further comprising HMOs, and wherein undesirable segregation is prevented. Summary of the Invention

[0012] A study was conducted on the segregation behavior of powdered milk formula compositions containing human milk oligosaccharides (HMOs). The inventors of the present invention observed that, while conventional compositions containing fat droplets with a low volume-weighted mode diameter (below 1 μm) suffer from undesirable segregation, it was unexpectedly found that this segregation is reduced when using a composition in which the fat droplet diameter is increased (i.e., a product in which the volume-weighted mode diameter of the lipid globules is greater than 1 μm and / or in which the majority of the globules have a diameter of at least 2 μm and up to 12 μm).

[0013] The inventors have found that dairy formula particles comprising the large lipid globules reduce powder segregation in a powdered nutritional composition comprising both the dairy formula particles and the HMO particles when the particle sizes of the dairy formula particles and the HMO particles are different.

[0014] The inventors have discovered that the volume-weighted diameter of the lipid globules of the milk powder particles of the nutritional compositions according to the present invention, as well as the powder particle size distribution of the milk powder particles, are both larger than the powder particle size distribution and lipid globule mode diameter of conventional nutritional compositions combined with HMO particles. The HMO particles have a different, smaller particle size distribution than the milk formula particles according to the present invention, which contain large lipid globules. Surprisingly, the larger particle size distribution of the milk formula particles does not lead to increased segregation in compositions also containing HMO particles. This is significant because, when containing these HMO particles, the particle size variation in the nutritional compositions according to the present invention is greater than in prior art nutritional compositions, and therefore does not conform to expectations based on physical theory of powder segregation.

[0015] While the inventors do not wish to be bound by theory, it is believed that the large lipid globules may have some form of interaction with the HMOs, thereby preventing powder segregation.

[0016] Thus, the present invention provides a powdered nutritional composition comprising (i) milk formula particles comprising lipid, protein, digestible carbohydrates, and (ii) HMO particles, wherein the nutritional composition is selected from infant formula, follow-up formula and growing-up milk, wherein the nutritional composition is not human milk, and wherein the lipids in the milk formula particles are in the form of lipid globules, and

[0017] a. The mode diameter of the lipid globules is at least 1 μm based on volume, and / or

[0018] b. At least 40% by volume of the lipid globules have a diameter of 2 to 12 μm, and wherein the HMO particles comprise at least 2'FL.

[0019] The present invention provides a powdered nutritional composition comprising milk formula particles containing lipids, proteins, and digestible carbohydrates, and HMO particles.

[0020] wherein the nutritional composition is selected from the group consisting of infant formula, stage two formula, and growing-up milk, wherein the nutritional composition is not human milk, and wherein the lipids in the milk formula particles are in the form of lipid globules, and

[0021] a. The mode diameter of the lipid globules is at least 1 μm based on volume, and / or

[0022] b. at least 40% by volume of the lipid globules have a diameter of 2 to 12 μm,

[0023] wherein the HMO comprises at least 2'FL, and wherein

[0024] The powder particle size distribution of the milk formula particles comprises a Dx(10) of at least 60 μm and / or a Dx(50) of at least 200 μm and / or a Dx(90) of at least 400 μm.

[0025] The present invention also provides methods for preparing such nutritional compositions, products obtained therewith (including reconstituted products) and uses thereof.

[0026] The present invention also relates to the use of milk formula particles for reducing powder segregation in a powdered nutritional composition, the nutritional composition comprising (i) milk formula particles comprising lipid, protein, digestible carbohydrates, and (ii) HMO particles, wherein the nutritional composition is selected from the group consisting of infant formula, stage 2 formula and growing-up milk, wherein the nutritional composition is not human milk, wherein the lipids in the milk formula particles are in the form of lipid globules, and

[0027] a. The mode diameter of the lipid globules is at least 1 μm based on volume, and / or

[0028] b. at least 40% by volume of the lipid globules have a diameter of 2 to 12 μm,

[0029] And wherein the HMO particle comprises at least 2'fucosyllactose (2'FL).

[0030] In a preferred aspect of the present invention, the use of milk formula particles further relates to (i) milk formula particles of a nutritional composition having a powder particle size distribution comprising a Dx(10) of at least 60 μm and / or a Dx(50) of at least 200 μm and / or a Dx(90) of at least 400 μm.

[0031] The present invention also provides a nutritional composition (preferably a powdered nutritional composition) for promoting metabolic health, promoting the development of good body composition, preventing the development of obesity later in life, promoting balanced growth, promoting lean growth, promoting cognitive development, improving brain health, improving intestinal health, providing beneficial prebiotic effects, improving immune cell function and enhancing immune health, preventing infection or improving recovery from infection, stimulating intestinal barrier function / epithelial cell regulators to improve intestinal health, and reducing the risk of intestinal health problems and / or improving recovery from intestinal health problems, the nutritional composition comprising (i) milk formula particles comprising lipids, proteins, and digestible carbohydrates, and (ii) HMO particles,

[0032] wherein the nutritional composition is selected from the group consisting of infant formula, stage two formula, and growing-up milk, wherein the nutritional composition is not human milk, and wherein the lipids in the milk formula particles are in the form of lipid globules, and

[0033] a. The mode diameter of the lipid globules is at least 1 μm based on volume, and / or

[0034] b. at least 40% by volume of the lipid globules have a diameter of 2 to 12 μm,

[0035] The HMO particles comprise at least 2'FL.

[0036] Reducing and preventing the segregation of each component in the nutritional product has higher benefits for consumers. Segregation may be visual (the larger particles in the composition are separated from the smaller particles), and can reduce the consumer's liking for the product. When there is no segregation, the consumer will know that for each bottle of product they make, the composition will be basically the same, and therefore reliable and enough nutritional quality is provided. The consumer is more likely to discard the product that suffers from segregation because they think that the composition has gone bad. Therefore, the nutritional composition according to the present invention that does not suffer from this shortcoming has obtained better support and use, and does not suffer from the shortcoming associated with the nutritional composition of segregation. In addition, the product will be more stable, and therefore has the shelf life characteristics of improvement.

[0037] For certain jurisdictions, the invention may also be expressed as a method for (therapeutic) promoting metabolic health, promoting the development of good body composition, preventing the development of obesity later in life, promoting balanced growth, promoting lean growth, promoting cognitive development, improving brain health, improving gut health, providing beneficial prebiotic effects, enhancing immune cell function and promoting immune health, preventing infection or improving recovery from infection, stimulating intestinal barrier function / epithelial cell regulators to improve gut health, and reducing the risk of and / or improving recovery from gut health problems.

[0038] For certain jurisdictions, the present invention may also be expressed as the use of lipids, proteins, digestible carbohydrates, and HMOs (wherein the HMOs contain at least 2'FL) in the manufacture of a nutritional composition for promoting metabolic health, promoting the development of good body composition, preventing the development of obesity later in life, promoting balanced growth, promoting lean growth, promoting cognitive development, improving brain health, improving intestinal health, providing beneficial prebiotic effects, enhancing immune cell function and promoting immune health, preventing infection or improving recovery from infection, stimulating intestinal barrier function / epithelial cell regulators to improve intestinal health, and reducing the risk of intestinal health problems and / or improving recovery from intestinal health problems, wherein the nutritional composition is an infant formula or a second formula or a growing-up milk and comprises lipid globules, and

[0039] a. The volume-weighted mode diameter of the lipid globules is at least 1.0 μm, and / or

[0040] b. At least 40% by volume of the lipid globules have a diameter of 2 to 12 μm.

[0041] In other words, the present invention also relates to the use of the nutritional composition according to the present invention for promoting metabolic health, promoting the development of a good body composition, preventing the development of obesity later in life, promoting balanced growth, promoting lean growth, promoting cognitive development, improving brain health, improving intestinal health, providing beneficial prebiotic effects, improving immune cell function and enhancing immune health, preventing infection or improving recovery from infection, stimulating intestinal barrier function / epithelial cell regulators and thereby improving intestinal health, as well as reducing the risk of intestinal health problems and / or improving recovery from intestinal health problems.

[0042] List of Examples

[0043] 1. A powdered nutritional composition comprising (i) milk formula particles comprising lipid, protein, digestible carbohydrates, and (ii) human milk oligosaccharide (HMO) particles, wherein the nutritional composition is selected from the group consisting of infant formula, follow-up formula, and growing-up milk, wherein the nutritional composition is not human milk, and wherein the lipid in the milk formula particles is in the form of lipid globules, and

[0044] a. The mode diameter of the lipid globules is at least 1 μm based on volume, and / or

[0045] b. at least 40% by volume of these lipid globules have a diameter of 2 to 12 μm,

[0046] And wherein the HMO particles comprise at least 2'fucosyllactose (2'FL).

[0047] 2. The nutritional composition according to embodiment 1, wherein the powder particle size distribution of the milk formula particles comprises a Dx(10) of at least 60 μm and / or a Dx(50) of at least 200 μm and / or a Dx(90) of at least 400 μm.

[0048] 3. The nutritional composition according to embodiments 1 and 2, wherein the powder particle size distribution of the HMO particles comprises a Dx(10) of at least 5 μm and / or a Dx(50) of at least 40 μm and / or a Dx(90) of at most 315 μm.

[0049] 4. The nutritional composition according to the preceding embodiment, wherein the (i) milk formula particles and the (ii) HMO particles have a Euclid difference greater than 0.2.

[0050] 5. The nutritional composition according to the preceding embodiment, wherein the difference between Dx(20) of the milk formula particles and Dx(80) of the HMO particles is at least 10 μm.

[0051] 6. The nutritional composition of any one of embodiments 1 to 5, wherein the lipid globules comprise a coating comprising phospholipids and / or wherein the amount of phospholipids is 0.5-20% by weight of the total lipid content.

[0052] 7. The nutritional composition according to embodiment 6, wherein the phospholipids are derived from milk fat globule membrane (MFGM) or are provided as MFGM, preferably bovine milk MFGM.

[0053] 8. The nutritional composition of embodiments 1 to 7, wherein i) the lipid comprises linoleic acid and α-linolenic acid in a weight ratio of 2 to 20, and / or ii) the lipid comprises at least 10 wt% palmitic acid based on total lipid, and at least 15 wt% of this palmitic acid, based on total palmitic acid, is esterified to the sn-2 position of the triglyceride.

[0054] 9. The nutritional composition according to embodiments 1 to 8, wherein the (ii) HMO particles are present in an amount of 0.1-2 wt.%, preferably 0.3-1 wt.%, based on the weight of dry matter.

[0055] 10. The nutritional composition according to embodiments 1 to 9, wherein the lipid contains both vegetable fat and milk fat, preferably in a weight ratio of 30:70 to 90:10.

[0056] 11. The nutritional composition of embodiments 1 to 10, wherein the amount of lipids is 10-30 wt% of the dry matter, the amount of protein is 9.6-12 wt% of the dry matter, the amount of carbohydrates is 40-70 wt% of the dry matter, and the amount of phospholipids is 0.5-3 wt% based on the total fat weight.

[0057] 12. The nutritional composition according to embodiments 1 to 11, wherein the HMOs comprise 2'FL and at least one selected from the group consisting of lacto-N-neotetraose (LNnT), p-lactose-N-neohexaose (p-LNnH), sialic acid, 3' sialyllactose (3'SL) and 6' sialyllactose (6'SL), 3' fucosyllactose (3-FL), difucosyllactose (DFL), lacto-N-fucopentaose (LNFP, such as lacto-N-fucopentaose), lacto-N-fucopentaose (LNFP), and lacto-N-fucopentaose (LNFP). Pentasaccharide II, lactose-N-fucopentaose III, lactose-N-fucopentaose V), lactose-N-fucohexaose, lactose-N-difucohexaose (LNDFH, such as lactose-N-difucohexaose I and lactose-N-difucohexaose II), sialic acid-lactose-N-tetraose (LSTa), sialic acid-lactose-N-tetraose b (LSTb), sialic acid-lactose-N-tetraose c (LSTc), disialyl lactose-N-tetraose (DSLNT), lactose-N-neodifucohexaose (LNnDFH

[00145] In some embodiments, the present invention relates to a fucosyllactose-N-hexaose, a fucosyllactose-N-neohexa ...

[0058] 13. The nutritional composition according to the preceding embodiment, further comprising additional non-digestible carbohydrates, preferably one or more from the group of FOS and GOS carbohydrates.

[0059] 14. The nutritional composition according to the preceding embodiment, obtainable by dry mixing the HMO particles, and optionally at least part of the digestible carbohydrates and optionally the non-digestible carbohydrates, and a base powder comprising large lipid globules and at least part of the protein and optionally at least part of the digestible carbohydrates.

[0060] 15. The nutritional composition according to embodiment 14, wherein the base powder is obtainable by metering the lipid into an aqueous phase comprising protein and optionally part of the digestible carbohydrates and at least part of the phospholipids, mixing the combined aqueous and lipid phases to obtain an emulsion, and subsequently drying the emulsion, preferably in a spray dryer.

[0061] 16. A method for preparing the nutritional composition according to any one of embodiments 1 to 15, comprising the following steps:

[0062] a) preparing a base powder, wherein the digestible carbohydrates are optionally included in the base powder, added as solids in a dry mixing step, or both, and

[0063] b) dry-mixing said base powder comprising at least the lipid globules and protein with the HMO particles comprising at least 2'FL.

[0064] 17. The method according to embodiment 16, wherein the base powder is prepared by: a) providing an aqueous phase having a dry matter content of 10% to 60% by weight (based on the total weight of the aqueous phase), which comprises at least one protein component, b) providing a liquid lipid phase comprising at least one lipid, and c) mixing the lipid phase with the aqueous phase in a ratio of 5% to 50% by weight using a mixer to provide an oil-water emulsion, and d) drying the emulsion obtained in step c).

[0065] 18. The method according to embodiments 16 and 17, wherein additional ingredients selected from the group of vitamins, minerals, digestible carbohydrates, and additional (non-digestible) oligosaccharides are dry-mixed with the base powder and the HMOs.

[0066] 19. A product obtainable by the process according to any one of embodiments 16 to 18.

[0067] 20. The nutritional composition of embodiments 1 to 15 and 19, wherein the powdered nutritional composition is reconstituted with water or other food grade aqueous liquid to form a ready-to-drink liquid.

[0068] 21. The nutritional composition of embodiments 1 to 15, 19, and 20 for use in promoting metabolic health, promoting the development of good body composition, preventing the development of obesity later in life, promoting balanced growth, promoting lean growth, promoting cognitive development, improving brain health, improving gut health, providing beneficial prebiotic effects, enhancing immune cell function and improving immune health, preventing infection or improving recovery from infection, stimulating intestinal barrier function / epithelial cell regulators to improve gut health, and reducing the risk of and / or improving recovery from gut health problems.

[0069] 22. Use of milk formula particles for reducing powder segregation in a powdered nutritional composition, the nutritional composition comprising (i) milk formula particles comprising lipid, protein, digestible carbohydrates, and (ii) HMO particles, wherein the nutritional composition is selected from infant formula, follow-up formula and growing-up milk, wherein the nutritional composition is not human milk, wherein the lipid in the milk formula particles is in the form of lipid globules, and

[0070] a. The mode diameter of the lipid globules is at least 1 μm based on volume, and / or

[0071] b. at least 40% by volume of these lipid globules have a diameter of 2 to 12 μm,

[0072] And wherein the HMO particles comprise at least 2'fucosyllactose (2'FL). DETAILED DESCRIPTION

[0073] As used herein, the following terms have the following meanings.

[0074] Infants are children under 12 months of age.

[0075] "Infant formula" or "second stage formula" or "toddler formula" means that it relates to an artificially made composition, or in other words, it is a synthetic composition (that is, the synthetic composition is not breast milk). Therefore, the nutritional composition administered is an artificial infant formula or an artificial second stage formula or an artificial toddler formula or a synthetic infant formula or a synthetic second stage formula or a synthetic toddler formula. Infant formula refers to an artificially made nutritional composition intended for infants aged 0 to about 4 to 6 months, and is intended as a substitute for human milk. Typically, infant formula is suitable for use as a sole source of nutrition. Such infant formula is also referred to as first stage formula.

[0076] Second stage formulas are used for infants from 4 to 6 months up to 12 months of age and are intended to be a supplement to other foods when infants are starting to wean themselves off breast milk. Infant formulas and second stage formulas are subject to strict regulations, such as EU Regulations No. 609 / 2013 and 2016 / 127.

[0077] Toddlers are children between the ages of one and three, also known as toddlers.

[0078] Infant formula refers to an artificially prepared nutritional composition intended for infants between 12 and 36 months of age, which is intended as a complementary feeding for infants.

[0079] The term "HMO" or "multiple HMOs" refers to one or more human milk oligosaccharides. These carbohydrates are highly resistant to enzymatic hydrolysis and have biological functions that are not directly related to their caloric value. HMOs play a key role in the early development of infants and young children, including the maturation of the immune system. Human milk contains many different types of HMOs, and to date, more than 130 different types have been identified. HMOs are based on various combinations of glucose, galactose, sialic acid (N-acetylneuraminic acid), fucose and / or N-acetylglucosamine, most of which have a lactose moiety at their reducing end. Sialic acid and / or fucose (when present) occupy the terminal position of the non-reducing end. HMOs can be further divided into acidic (such as oligosaccharides containing charged sialic acid) or neutral (such as fucosylated oligosaccharides). In the context of the present invention, lactose is not considered an HMO species. HMOs can be produced by means known in the art.

[0080] "Fucosylated oligosaccharides" are neutral oligosaccharides having a fucose residue. Examples of fucosylated oligosaccharides are 2'FL (2'-fucosyllactose), 3-FL (3-fucosyllactose), difucosyllactose, lacto-N-fucopentaose (e.g., lacto-N-fucopentaose I, lacto-N-fucopentaose II, lacto-N-fucopentaose III, lacto-N-fucopentaose V), lacto-N-fucohexaose, lacto-N-difucohexaose I, fucosyllactose-N-hexaose, fucosyllactose-N-neohexaose, difucosyllactose-N-hexaose I, difucosyllactose-N-neohexaose II, and any combination thereof.

[0081] Fucosyllactose (FL) is a non-digestible oligosaccharide found in human milk. It is not found in cow's milk. It consists of three monosaccharide units (fucose, galactose, and glucose) linked together. Lactose is a galactose unit linked to a glucose unit via a β1,4 linkage. The fucose unit is further linked to the galactose unit of the lactose molecule via an α1,2 linkage (2'-fucosyllactose, 2'-FL, Fucα1-2Galβ1-4Glc) or to the glucose unit of lactose via an α-1,3 linkage (3-fucosyllactose, 3-FL, Galβ1-4(Fucα1-3)Glc).

[0082] "One or more N-acetylated oligosaccharides" encompass both "N-acetyl-lactosamine" and "one or more oligosaccharides containing N-acetyl-lactosamine". These are neutral oligosaccharides having an N-acetyl-lactosamine residue. Suitable examples are LNT (lactose-N-tetraose), p-lactose-N-neohexaose (p-LNnH), LNnT (lactose-N-neotetraose) and any combination thereof. Other examples are lactose-N-hexaose, lactose-N-neohexaose, p-lactose-N-hexaose, p-lactose-N-neohexaose, lactose-N-octose, lactose-N-neooctose, iso-lactose-N-octose, p-lactose-N-octose and lactose-N-decaose.

[0083] "Sialyl oligosaccharides" are oligosaccharides containing charged sialic acid, i.e., oligosaccharides with sialic acid residues. They are acidic. Some examples are 3-SL (3' sialyllactose) and 6-SL (6' sialyllactose).

[0084] As used herein in the context of powder particle size distribution, percentile Dx(10) is the maximum particle size below which 10% of the sample volume exists. Dx(50) is the maximum particle size below which 50% of the sample volume exists, and is also referred to as the median particle size by volume. Similarly, Dx(90) is the maximum particle size below which 90% of the sample volume exists. Likewise, a percentile Dx(Y) can be determined, where Y% of the sample volume is below this value.

[0085] The particle size distribution of a powder sample can be determined using laser diffraction techniques with the aid of an apparatus such as the Malvern Mastersizer 3000.

[0086] As used herein, Euclidean difference refers to the normalized Euclidean distance statistic to quantify the difference between logarithmic ratio particle size distributions a and b (where a and b are different powders). The Euclidean difference is mathematically determined by the following formula

[0087] (I)

[0088]

[0089] where D is the number of particle size classes (D = 101 for the Malvern 3000 using the default bin size distribution).

[0090] The threshold used here as a cut-off value for powders having different distributions is preferably at least greater than 0.2. The higher the Euclidean difference, the greater the difference in distribution between the two powders.

[0091] The nutritional composition according to the present invention is selected from infant formula, second stage formula, and growing-up milk. This means that the nutritional composition of the present invention is not human milk. Alternatively, the term "formulated food" means that it relates to an artificially made or, in other words, synthetic composition. Therefore, in one embodiment, the nutritional composition is selected from artificial infant formula, artificial second stage formula, and artificial growing-up milk or synthetic infant formula, synthetic second stage formula, and synthetic growing-up milk.

[0092] In this document and its claims, the verb "to comprise" and its conjugations are used in its non-restrictive sense to mean including the items following the word, but not excluding items not specifically mentioned. Furthermore, unless the context clearly requires the presence of one and only one element, reference to an element by the indefinite article "a" or "an" does not exclude the possibility that more than one of the element may be present. Thus, the indefinite article "a" or "an" generally means "at least one."

[0093] Formulated foods

[0094] The nutritional composition according to the present invention is in the form of an infant formula, a second stage formula, or a toddler formula. This means that the composition administered is not human milk. This also means that the nutritional composition is not natural cow's milk or natural milk from another mammal. In the context of the present invention, toddler formula can also be named as growing-up milk.

[0095] Alternatively, as used herein, the term "infant formula" or "second stage formula" or "toddler formula" means that it relates to a composition that is artificially made or, in other words, synthetic. Thus, in one embodiment, the nutritional composition administered is an artificial infant formula or an artificial second stage formula or an artificial toddler formula or a synthetic infant formula or a synthetic second stage formula or a synthetic toddler formula.

[0096] In the present invention, infant formula refers to a nutritional composition artificially made, intended for 0 months to about 4 months to 6 months of age infants, and is intended as a substitute for human milk. Typically, infant formula is suitable for use as a sole source of nutrition. Such infant formula is also referred to as first stage formula. The second stage formula for the infant starting from 4 months to 6 months of birth to 12 months of birth is intended to be the supplementary feeding on other foods of the infant starting weaning. Infant formula and the second stage formula are subject to strict regulations, such as EU regulations No. 609 / 2013 and No. 2016 / 127. In this article, infant formula refers to a nutritional composition artificially made, intended for 12 months to 36 months of age infants, and is intended as the supplementary feeding of infants.

[0097] The nutritional composition is preferably an infant formula or a stage 2 formula. More preferably, the nutritional composition is an infant formula.

[0098] The nutritional composition comprises digestible carbohydrates, protein and lipids, wherein lipids preferably provide 30% to 60% of the total calories, protein provides 5% to 20% of the total calories, and digestible carbohydrates provide 25% to 75% of the total calories.

[0099] The nutritional composition is preferably an infant formula or a second formula and preferably comprises 3 to 7 g lipid / 100 kcal, preferably 4 to 6 g lipid / 100 kcal, more preferably 4.5 to 5.5 g lipid / 100 kcal, preferably 1.7 to 3.5 g protein / 100 kcal, more preferably 1.8 to 2.1 g protein / 100 kcal, more preferably 1.8 to 2.0 g protein / 100 kcal, and preferably 5 to 20 g digestible carbohydrates / 100 kcal, preferably 6 to 16 g digestible carbohydrates / 100 kcal, more preferably 10 to 15 g digestible carbohydrates / 100 kcal.

[0100] Preferably, the nutritional composition is an infant formula or a second stage formula and, when in ready-to-drink form, preferably has an energy density of 60 to 75 kcal / 100 ml, more preferably 60 to 70 kcal / 100 ml. This density ensures an optimal balance between hydration and calorie intake.

[0101] The nutritional composition is a solid product, preferably a powder. Suitably, the nutritional composition is in powder form that can be reconstituted with water or other food-grade aqueous liquids to form a ready-to-drink liquid. The lipid globules were found to maintain their size and coating upon reconstitution. It was further found that the nutritional composition having milk formula particles and HMO particles according to the present invention did not suffer from segregation.

[0102] The nutritional composition according to the present invention comprises milk formula particles containing carbohydrates, protein and lipid, wherein preferably lipid provides 30% to 60% of the total calories, protein provides 5% to 20% of the total calories and carbohydrates provide 25% to 75% of the total calories. Preferably, the nutritional composition comprises 10% to 50% by weight of lipid based on the dry weight of the total composition.

[0103] The powdered nutritional composition preferably has a dry matter content of at least 90 wt.-%, more preferably 92.5-100 wt.-%, even more preferably 95-99.9 wt.-%.

[0104] Preferably, the powdered nutritional composition comprises 85-99.5 wt% of dairy formula particles, more preferably 90-99 wt% of dairy formula particles.

[0105] Preferably, the powdered nutritional composition comprises 0.1-3 wt% HMO particles, more preferably 0.15-2.5 wt% HMO particles.

[0106] The weight ratio between the milk formula particles and the HMO particles in the powdered nutritional composition is preferably at least 10:1, more preferably 25:1-1500:1, and most preferably 50:1-1000:1.

[0107] Preferably, the particle size distribution of the milk formula particles comprises a Dx(10) of 50 to 110 μm, preferably 50 to 90 μm, more preferably 60 to 80 μm, even more preferably 65 to 75 μm. In an embodiment, the milk formula particles comprise a Dx(10) of at least 50 μm, more preferably at least 60 μm, even more preferably at least 70 μm. The volume of the particles and their size distribution may suitably be determined using a particle size analyzer such as a Mastersizer 3000 (Malvern Instruments, Malvern, UK).

[0108] Preferably, the particle size distribution of the milk formula particles comprises a Dx(20) of 115 to 175 μm, preferably 115 to 145 μm, more preferably 120 to 140 μm, even more preferably 125 to 135 μm. In an embodiment, the milk formula particles comprise a Dx(20) of at least 115 μm, more preferably at least 120 μm, even more preferably at least 125 μm.

[0109] Preferably, the particle size distribution of the milk formula particles comprises a Dx(50) of 200 to 300 μm, preferably 200 to 260 μm, more preferably 210 to 250 μm, even more preferably 220 to 240 μm. In an embodiment, the milk formula particles comprise a Dx(50) of at least 200 μm, more preferably at least 210 μm, even more preferably at least 220 μm.

[0110] Preferably, the particle size distribution of the milk formula particles comprises a Dx(80) of 330 μm to 450 μm, preferably 330 μm to 370 μm, more preferably 340 μm to 360 μm, even more preferably 345 μm to 355 μm. In an embodiment, the milk formula particles comprise a Dx(80) of at least 330 μm, more preferably at least 340 μm, even more preferably at least 345 μm.

[0111] Preferably, the particle size distribution of the milk formula particles comprises a Dx(90) of 400 to 550 μm, preferably 400 to 460 μm, more preferably 410 to 450 μm, even more preferably 420 to 440 μm. In an embodiment, the milk formula particles comprise a Dx(90) of at least 400 μm, more preferably at least 410 μm, even more preferably at least 420 μm.

[0112] Preferably, the particle size distribution of the milk formula particles comprises a range of Dx(10) to Dx(90) of 50 μm to 550 μm, preferably 50 μm to 460 μm, more preferably 60 μm to 450 μm, even more preferably 70 μm to 440 μm. As used herein, Dx(10) is the diameter at which 10% of the volume of the composition consists of particles having a diameter less than this value, while Dx(90) is the diameter at which 90% of the volume of the composition consists of particles having a diameter less than this value; as used herein, the range of Dx(10) to Dx(90) is the range of diameters at which 80% of the volume of the powder consists of particles having a diameter within this range. Similarly, the range of Dx(20) to Dx(80) is the range of diameters at which 60% of the volume of the powder consists of particles having a diameter within said range.

[0113] Preferably, the particle size distribution of the HMO particles comprises a Dx(10) of 10 to 60 μm, more preferably 15 to 55 μm, even more preferably 20 to 50 μm. In an embodiment, the milk formula particles comprise a Dx(10) of at least 5 μm, more preferably at least 10 μm, even more preferably at least 15 μm.

[0114] Preferably, the particle size distribution of the HMO particles comprises a Dx(20) of 20 to 80 μm, more preferably 25 to 75 μm, even more preferably 30 to 70 μm. In an embodiment, the milk formula particles comprise a Dx(20) of at least 20 μm, more preferably at least 25 μm, even more preferably at least 30 μm.

[0115] Preferably, the particle size distribution of the HMO particles comprises a Dx(50) of 40 to 130 μm, more preferably 45 to 125 μm, even more preferably 50 to 120 μm. In an embodiment, the milk formula particles comprise a Dx(50) of at least 40 μm, more preferably at least 45 μm, even more preferably at least 50 μm.

[0116] Preferably, the particle size distribution of the HMO particles comprises a Dx(80) of 65 to 220 μm, more preferably 70 to 215 μm, even more preferably 75 to 210 μm. In an embodiment, the milk formula particles comprise a Dx(80) of at least 65 μm, more preferably at least 70 μm, even more preferably at least 75 μm.

[0117] Preferably, the particle size distribution of the HMO particles comprises a Dx(90) of 80 μm to 315 μm, more preferably 85 μm to 310 μm, even more preferably 90 μm to 305 μm. In an embodiment, the milk formula particles comprise a Dx(90) of at least 80 μm, more preferably at least 85 μm, even more preferably at least 90 μm.

[0118] Preferably, the particle size distribution of the HMO particles comprises a Dx(10) to Dx(90) range of 5 μm to 315 μm, more preferably 10 μm to 310 μm, even more preferably 15 μm to 305 μm.

[0119] In a preferred embodiment, the difference between the Dx(20) of the dairy formula particles and the Dx(80) of the HMO particles is at least 10 μm, more preferably at least 15 μm, even more preferably at least 20 μm. In other words, the Dx(20) of the dairy formula particles is at least 10 μm, more preferably at least 15 μm, even more preferably at least 20 μm higher than the Dx(80) of the HMO particles. The latter therefore means that at a specific Dx(80) value of the HMO particles, the Dx(20) of the dairy formula particles is at least 10 μm greater or higher, e.g., when the Dx(80) of the HMO particles is 80 μm, the Dx(20) of the dairy formula particles is at least 10 μm greater, i.e. at least 90 μm.

[0120] In a preferred aspect, the Dx(20) of the dairy formula particles is at least 5 μm higher than the Dx(50) of the HMO particles, more preferably at least 7.5 μm, and even more preferably at least 10 μm. In some embodiments, the Dx(20) of the dairy formula particles is at least 50 μm higher than the Dx(50) of the HMO particles. In other words, preferably, the difference between the Dx(20) of the dairy formula particles and the Dx(50) of the HMO particles is at least 5 μm, more preferably at least 7.5 μm, and even more preferably at least 10 μm.

[0121] Preferably, the Dx(50) of the milk formula particles is at least 2.5 times greater than the Dx(50) of the HMO particles. More preferably, the Dx(50) of the milk formula particles is at least 3 times greater than the Dx(50) of the HMO particles. Most preferably, the Dx(50) of the milk formula particles is at least 4 times greater than the Dx(50) of the HMO particles.

[0122] In another aspect, preferably, the Dx(10) of the dairy formula particles is at least 2 times the Dx(10) of the HMO particles. More preferably, the Dx(10) of the dairy formula particles is at least 2.5 times the Dx(10) of the HMO particles. Even more preferably, the Dx(10) of the dairy formula particles is at least 3 times the Dx(10) of the HMO particles. Most preferably, the Dx(50) of the dairy formula particles is at least 3.5 times the Dx(50) of the HMO particles.

[0123] Preferably, the Dx(90) of the milk formula particles is at least 2.5 times greater than the Dx(50) of the HMO particles. More preferably, the Dx(90) of the milk formula particles is at least 3 times greater than the Dx(90) of the HMO particles. Most preferably, the Dx(50) of the milk formula particles is at least 4 times greater than the Dx(90) of the HMO particles.

[0124] The Euclidean difference between the milk formula particles and the HMO particles is preferably greater than 0.2, more preferably at least 0.25, even more preferably at least 0.3.As used herein, the Euclidean difference provides a quantitative measure of the difference in particle size distribution between powders.

[0125] HMO

[0126] Human milk is rich in structurally diverse oligosaccharides (collectively referred to as human milk oligosaccharides (HMOs)), which support immune function in several ways. Thus, HMOs are (short) polymers of sugars (oligosaccharides), such as those in human breast milk, that can promote the development of the immune system, reduce pathogen infection, and improve brain development and cognition. In addition, HMOs are thought to shape the infant's gut microbiota by selectively stimulating bacteria (Bode et al., Human milk oligosaccharides: every baby needs a sugar mama. Glycobiology 2012; 22(9): 1147-1162). As used herein, HMOs are preferably in the form of HMO particles.

[0127] The nutritional composition according to the present invention comprises at least one type of HMO, namely 2'-fucosyllactose (2'FL).

[0128] In an embodiment, the HMO contained in the nutritional composition preferably comprises at least 40 wt%, more preferably at least 45 wt%, even more preferably at least 50 wt% 2'FL based on the total HMO weight.

[0129] In an alternative preferred embodiment, the HMO comprises 90-100 wt% 2'FL, even more preferably 95-100 wt% 2'FL, based on the total HMO weight.

[0130] One or more fucosylated oligosaccharides can be isolated from natural sources (such as animal milk) by chromatography or filtration techniques. Alternatively, they can be produced by biotechnological means using specific fucosyltransferases and / or fucosidases using enzyme-based fermentation techniques (recombinant or natural enzymes) or microbial fermentation techniques known in the art. In the latter case, the microorganism can express its natural enzyme and substrate, or can be engineered to produce the corresponding substrate and enzyme. Single microbial cultures and / or mixed cultures can be used. Fucosylated oligosaccharide formation can start from any degree of polymerization (DP) from the acceptor substrate, starting from DP=1. Alternatively, fucosylated oligosaccharides can be produced by chemical synthesis from lactose and free fucose. Fucosylated oligosaccharides can also be obtained, for example, from Kyowa, Hakko, Kogyo of Japan, Friesland Campina, The Netherlands, Glycom DSM, Denmark, and Chr. Hansen, Denmark.

[0131] In an embodiment, the HMO contained in the nutritional composition may further comprise at least one other oligosaccharide, preferably an N-acetylated oligosaccharide, in addition to 2'FL. One or more types of N-acetylated oligosaccharides may be present. The one or more N-acetylated oligosaccharides may be selected from lacto-N-tetraose (LNT), lacto-N-neotetraose (LNnT), or any combination thereof. In some specific embodiments, the N-acetylated oligosaccharide is lacto-N-neotetraose (LNnT), p-lacto-N-neohexaose (p-LNnH), or any combination thereof.

[0132] In an embodiment, the N-acetylated oligosaccharide is LNnT. In an embodiment, the HMO contained in the nutritional composition preferably comprises 10-40 wt% LNnT, more preferably 15-35 wt% LNnT, even more preferably 20-30 wt% LNnT based on the total HMO weight.

[0133] In preferred embodiments, the N-acetylated oligosaccharide is LNT. In embodiments, the HMO preferably comprises 10-40 wt% LNT, more preferably 15-35 wt% LNT, and even more preferably 20-30 wt% LNT, based on the total HMO weight. In particularly advantageous embodiments of the present invention, the HMO contained in the nutritional composition comprises 2'-fucosyllactose (2FL) and lacto-N-neotetraose (LNnT).

[0134] In some other specific embodiments, the N-acetylated oligosaccharide is a mixture of LNT and LNnT. In some specific embodiments, the composition comprises both LNT and LNnT in a LNT:LNnT ratio of 5:1 to 1:2, or 2:1 to 1:1, or 2:1.2 to 2:1.6.

[0135] One or more N-acetylated oligosaccharides can be synthesized by enzymatic transfer of sugar units using glycosyltransferases as described in US 5288637, or by other conversion methods known in the art. Suitable N-acetylated oligosaccharides for use in the preparation and nutritional composition according to the present invention include commercially available variants such as those from DSM Glycom and Chr. Hansen.

[0136] In a particular embodiment, the HMOs of the nutritional composition according to the invention may comprise one or more sialylated oligosaccharides.One or several sialylated oligosaccharides may be present.

[0137] The sialylated oligosaccharide may be selected from the group consisting of 3'-sialyllactose (3'SL), 6'-sialyllactose (6'SL), and any combination thereof. In some embodiments of the present invention, the composition comprises 3'SL and 6'SL. In some specific embodiments, the ratio of 3'-sialyllactose (3'SL) to 6'-sialyllactose (6'SL) may range from 5:1 to 1:10, or from 3:1 to 1:1, or from 1:1 to 1:10.

[0138] The composition according to the present invention may also optionally include at least one oligosaccharide precursor. One or more oligosaccharide precursors may be present. For example, human milk oligosaccharide precursors are sialic acid, fucose, or a mixture thereof. In some specific embodiments, the composition includes sialic acid.

[0139] In another embodiment, the HMO comprises 2'FL and one or more additional HMO components. The HMO component comprises 2'FL and may comprise at least one, preferably more, selected from the group consisting of sialic acid (SA), lactose-N-neotetraose (LNnT), p-lactose-N-neohexaose (p-LNnH), sialic acid, 3' sialyllactose (3'SL) and 6' sialyllactose (6'SL), 3' fucosyllactose (3-FL), difucosyllactose (DFL), lactose-N-fucopentaose (LNFP, such as lactose-N-fucopentaose I), lactose-N-fucopentaose (LNFP), and lactose-N-fucopentaose (LNFP). I, lactose-N-fucopentaose III, lactose-N-fucopentaose V), lactose-N-fucohexaose, lactose-N-difucohexaose (LNDFH, such as lactose-N-difucohexaose I and lactose-N-difucohexaose II), sialic acid lactose-N-tetraose (LSTa), sialic acid lactose-N-tetraose b (LSTb), sialic acid lactose-N-tetraose c (LSTc), disialyl lactose-N-tetraose (DSLNT), lactose-N-neodifucohexaose (LNnDFH I), fucosyllactose-N-hexaose, fucosyllactose-N-neohexaose (such as fucosyllactose-N-neohexaose I, fucosyllactose-N-neohexaose II), difucosyllactose-N-hexaose I, difucosyllactose-N-neohexaose, difucosyllactose-N-neohexaose I, difucosyllactose-N-neohexaose II, fucosyl-p-lactose-N-hexaose and trifucosyllactose-p-lactose-N-hexaose I, and lactose-N-tetraose (LNT), or any combination thereof. In some specific embodiments, the HMO component comprises 2'FL and one or more of: 3'fucosyllactose (3-FL), lacto-N-tetraose (LNT), lacto-N-neotetraose (LNnT), difucosyllactose (DFL), 3'sialyllactose (3'SL), and 6'sialyllactose (6'SL).

[0140] Exemplary HMO combinations include, but are not limited to: SA, 3'SL, 6'SL, 3-FL, 2'FL, and LNnT; SA, 3'SL, 6'SL, 3-FL, 2'FL, LNT, and LNnT; SA, 3'SL, 6'SL, 3-FL, 2'FL, DFL, LNT, and LNnT; 3'SL, 6'SL, 3-FL, 2'FL, DFL, LNT, and LNnT; 3'SL, 6'SL, 3-FL, 2'FL, and LNnT; 3'SL, 6'SL, 3-FL, 2'FL, and LNT; 3'SL, 6'SL, 3-FL, 2'FL, and DFL; 3'SL, 6'SL, 2'FL, LNT and DFL; SA, 6'SL, 3-FL, 2'FL, and LNnT; SA, 6'SL, 3-FL, 2'FL, and LNT; SA, 6'SL, 3-FL, 2'FL, and DFL; SA, 3'SL, 3-FL, 2'FL, and LNnT; SA, 3'SL, 6'SL, 2'FL, and LNnT SA, 3'SL, 6'SL, 2'FL and LNT; SA, 3'SL, 6'SL, 2'FL and DFL; SA, 3'SL, 6'SL, 3-FL and 2'FL; SA and 2'FL; 3'SL and 2'FL; SA, 6'SL and 2'FL; SA, 3-FL and 2'FL; SA, 2'F L and LNnT; 2'FL and LNT, 2'FL and DFL, SA, 3'SL, 6'SL and 2'FL; SA, 3'SL, 3-FL and 2'FL; SA, 3'SL, 2'FL and LNnT; SA, 6'SL, 3-FL and 2'FL; SA, 6'SL, 2'FL and LNnT; SA SA, 3'SL, 3-FL, 2'FL and LNnT; SA, 3'SL, 6'SL, 2' FL and LNnT; 3'SL, 6'SL, 3-FL and 2'FL; 3'SL, 6'SL, 2'FL and LNnT; 3'SL, 3-FL, 2'FL and LNnT; 3'SL, 3-FL and 2'FL; 3'SL, 2'FL and LNnT; 3'SL, 2'FL and LNT; 3'SL, 2'FL and DFL; 3'SL, 6'SL and 2'FL; 3'SL and 3-FL; 3'SL and 2'FL; 6'SL and 2'FL; 6'SL, 3-FL, 2'FL and LNnT; 3-FL, 2'FL and LNnT; 2'FL and LNT; 2'FL and DFL, and 2'FL and LNnT.

[0141] In a preferred aspect, in addition to 2'FL, the HMO may be selected from 3-FL (3-fucosyllactose), 6'SL (6-sialyllactose), 3'SL (3'-sialyllactose), LNT (lacto-N-tetraose), LNnT (lacto-N-neotetraose) and difucosyllactose (DFL).

[0142] In a preferred embodiment, the HMO comprises 40-60 wt% 2'FL, 10-20 wt% 3-FL, 2-7 wt% 3'SL, 4-8 wt% 6'SL, and 20-30 wt% LNT, based on the total HMO weight.

[0143] In embodiments where both 2'-fucosyllactose (2'FL) and 3'-fucosyllactose (3-FL) are incorporated into the composition, they are preferably used in a 2'FL:3-FL weight ratio of at least 2.5: 1. When 3'-sialyllactose (3'SL) is incorporated into the composition, it is preferably in a 2'FL:3'SL weight ratio of at least 11.2: 1. When 6'-sialyllactose (6'SL) is included in the composition, it is preferably in a 2'FL:6'SL weight ratio of at least 1.8: 1.

[0144] In a preferred embodiment of the present invention, the HMOs may be present in an amount of 300-2500 μg / ml of the reconstituted powder composition, more preferably 400-2200 μg / ml, and even more preferably 750-2000 μg / ml of the composition. In a specific embodiment, the amount of the HMO mixture is 1500-2000 μg / ml of the composition. Such amounts are particularly sufficient for complete nutrition (such as infant formula, second stage formula, or in the case of growing-up milk).

[0145] In the case where the nutritional composition is in powder form, HMO may preferably be present in an amount in the range of 300 mg / 100 g dry weight to 1400 mg / 100 g dry weight, preferably in the range of 450 mg / 100 g dry weight to 1250 mg / 100 g dry weight. When expressed in calorie-based amounts, preferably the nutritional composition according to the present invention comprises HMO in a concentration in the range of 60 mg / 100 kcal to 300 mg / 100 kcal, preferably in the range of 100 mg / 100 kcal to 270 mg / 100 kcal.

[0146] In one embodiment, the amount of HMOs provided in the nutritional composition of the present invention is such that normal consumption of the nutritional composition would provide an infant or toddler, respectively, with a total daily dose thereof of 0.1 to 10 g, such as 0.2-9 g, 0.3-8 g, 0.4-7 g, 0.5-6 g, 0.6-5 g, 0.8-3 g, 0.9-2 g, or 1 to 1.5 g per day.

[0147] Preferably, the nutritional composition according to the present invention comprises 2'FL at a concentration in the range of 200 μg / ml - 1500 μg / ml, more preferably in the range of 250 μg / ml - 1250 μg / ml upon reconstitution.

[0148] When expressed as an amount based on dry weight, the nutritional composition according to the present invention preferably comprises 2'FL in a concentration range of 175 mg / 100 g dry weight to 1125 mg / 100 g dry weight, preferably in a range of 560 mg / 100 g dry weight to 940 mg / 100 g dry weight. When expressed as an amount based on calories, the nutritional composition according to the present invention preferably comprises 2'FL in a concentration range of 35 mg / 100 kcal to 225 mg / 100 kcal, preferably in a range of 50 mg / 100 kcal to 190 mg / 100 kcal.

[0149] As indicated for the individual HMOs, HMOs suitable for preparing the nutritional compositions according to the present invention are commercially available, for example, from Kyowa Hakko Kogyo Co., Ltd., FrieslandCampina AB, DSM Glycom, and Chr. Hansen AB. Otherwise, it is well within the capabilities of the skilled person to obtain the HMOs by isolation from a suitable source or by chemical synthesis using methods known in the art.

[0150] Base powder with large fat droplets

[0151] lipids

[0152] The nutritional composition for use according to the invention comprises milk powder particles comprising lipids present in globules as defined above.

[0153] The lipids of the present invention comprise one or more selected from the group consisting of triglycerides, polar lipids (such as phospholipids, cholesterol, glycolipids, sphingomyelin), free fatty acids, monoglycerides and diglycerides. Preferably, the composition comprises at least 70% by weight, more preferably at least 80% by weight, even more preferably at least 85% by weight of triglycerides, and most preferably at least 90% by weight of triglycerides based on the total lipids.

[0154] Lipid provides 30% to 60% of the total calories of preferably nutritional composition. More preferably, nutritional composition includes the lipid that 35% to 55% of total calories is provided, and even more preferably, nutritional composition includes the lipid that 40% to 50% of total calories is provided. Lipid is preferably with the amount of 3g to 7g / 100kcal, more preferably the amount of 4g to 6g lipid / 100kcal and most preferably the amount of 4.5g to 5.5g lipid / 100kcal exists. When in liquid form (for example, as reconstructed instant feeding liquid), nutritional composition preferably includes 2.1g to 6.5g lipid / 100ml, more preferably 3.0g to 4.0g / 100ml. Based on dry weight, nutritional composition preferably includes 10 weight % to 50 weight %, more preferably 12.5 weight % to 40 weight % lipid, even more preferably 19 weight % to 30 weight % lipid. In other words, when the nutritional composition is in powder form, the lipid is preferably present in an amount of 10-50g / 100g dry weight of the composition, more preferably 12.5-40g / 100g dry weight of the composition, even more preferably 19-30g / 100g dry weight of the composition.

[0155] Lipid preferably comprises vegetable lipid.The presence of vegetable lipid advantageously allows optimal fatty acid composition, high content of polyunsaturated fatty acids and / or is more like human milk fat.Lipid only from non-human mammal milk (for example, cow's milk) can not provide optimal fatty acid composition.In non-human mammal milk, the amount of essential fatty acids is too low.

[0156] Preferably, the nutritional composition comprises at least one, preferably at least two, plant lipid sources selected from the group consisting of flaxseed oil (linseed oil), rapeseed oil (such as colza oil, canola oil and rapeseed oil), sunflower oil, high oleic sunflower oil, safflower oil, high oleic safflower oil, olive oil, coconut oil, palm oil and palm kernel oil.

[0157] In a preferred embodiment, the nutritional composition comprises 30 to 90 wt% of vegetable lipids based on total lipids, more preferably 35 to 80 wt% based on total lipids, more preferably 40 to 70 wt% based on total lipids, more preferably 40 to 60 wt% of vegetable lipids.

[0158] The lipids in the nutritional composition preferably further comprise mammalian milk fat, preferably ruminant milk fat, more preferably the mammalian milk fat is derived from cow's milk, goat's milk, sheep's milk, buffalo's milk, yak's milk, reindeer's milk, and / or camel's milk, and most preferably the mammalian milk fat is cow's milk fat. Preferably, the mammalian milk fat is not human milk fat. Preferably, the mammalian milk fat comprises at least 70% triglycerides by weight, more preferably at least 90% triglycerides, and even more preferably at least 97% triglycerides by weight, based on the weight of the mammalian milk fat.

[0159] Preferably, the mammalian milk fat is derived from butter, butter fat, butter oil, and / or anhydrous milk fat, more preferably, the mammalian milk fat is derived from anhydrous milk fat and / or butter oil. Such mammalian milk fat sources have a higher triglyceride level. These mammalian milk fat sources may be in the form of a continuous lipid phase or a water-in-oil emulsion. The use of these mammalian milk fat sources during the manufacture of the nutritional composition of the present invention enables the formation of lipid globules, wherein each globule comprises a mixture of vegetable fat and mammalian milk fat.

[0160] Mammalian milk fat as used herein refers to all lipid components of milk produced by mammals (e.g., cows) and is present in commercial milk and milk-derived products. Butter as used herein is a water-in-oil emulsion consisting of more than 80% by weight of milk fat. Butter fat as used herein refers to all fat components of milk that can be separated by churning, in other words, all fat components present in butter. Anhydrous milk fat (AMF) is a term known in the art and refers to extracted milk fat. Typically, AMF contains more than 99% by weight of lipids, based on the total weight. It can be prepared by extracting milk fat from cream or butter. Anhydrous butter oil as used herein is synonymous with AMF. Butter oil is also a term known in the art. It typically refers to a milk fat extract having more than 98% by weight of lipids and is typically a precursor in the process of preparing anhydrous milk fat or anhydrous butter oil.

[0161] Preferably, the composition comprises 10 to 70 wt% mammalian milk fat based on total lipids, more preferably 20 to 65 wt% based on total lipids, more preferably 30 to 60 wt% based on total lipids, more preferably 40 to 60 wt% mammalian milk fat.

[0162] Preferably, the ratio of vegetable fat to mammalian milk fat ranges from 3 / 7 to 9 / 1.

[0163] In other words, in a preferred embodiment the lipid contains both vegetable fat and milk fat, preferably in a weight ratio of 30:70 to 90:10.

[0164] In a preferred embodiment, the lipids in the nutritional composition comprise:

[0165] a) 35% to 80% by weight of vegetable lipids, based on total lipids, and

[0166] b) 20% to 65% by weight of mammalian milk fat, based on total lipids, wherein the mammalian milk fat is selected from butter, butter fat, butter oil or anhydrous milk fat.

[0167] More preferably, the lipids in the nutritional composition comprise:

[0168] a) 40% to 70% by weight of vegetable lipids, based on total lipids, and

[0169] b) 30% to 60% by weight of mammalian milk fat, based on total lipids, wherein the mammalian milk fat is selected from butter, butter fat, butter oil or anhydrous milk fat.

[0170] Most preferably, the lipids in the nutritional composition comprise:

[0171] a) 40% to 60% by weight of vegetable lipids, based on total lipids, and

[0172] b) 40% to 60% by weight of mammalian milk fat, based on total lipids, wherein the mammalian milk fat is selected from butter, butter fat, butter oil or anhydrous milk fat.

[0173] The nutritional composition preferably further comprises fish oil, egg lipids, and one or more of a microbial oil, an algal oil, a fungal oil, or a single cell oil.

[0174] Compared to vegetable fats, mammalian milk fat is known to have a higher content of palmitic acid (PA) at the sn-2 position of triglycerides. In a preferred embodiment, the lipids in the nutritional composition comprise at least 10% by weight of PA based on total fatty acids, and at least 15% by weight of PA based on total palmitic acid is located at the sn-2 position of the triglycerides. Preferably, the amount of PA is less than 30% by weight based on total fatty acids. More preferably, the amount of PA is between 12% and 26% by weight, even more preferably between 14% and 24% by weight, based on total fatty acids.

[0175] Preferably, at least 15 wt% of PA, more preferably at least 20 wt% of PA, even more preferably at least 25 wt% of PA, and most preferably at least 30 wt% of PA, based on the total PA, is in the sn-2 or β position in the triglyceride. Preferably, the amount of PA in the sn-2 position in the triglyceride is no more than 45 wt%, preferably no more than 40 wt%, based on the total PA present in the lipid. Preferably, the amount of PA in the sn-2 position in the triglyceride is from 25 wt% to 40 wt%, based on the total PA.

[0176] Compared to plant fats, mammalian milk fat is known to have a higher content of the short-chain fatty acids (SCFAs) butyric acid (BA; C4:0) and caproic acid (CA; C6:0). In a preferred embodiment, the lipids in the nutritional composition comprise 0.6% to 5% by weight of SCFAs (i.e., the sum of BA and CA), based on total fatty acids. Preferably, the nutritional composition comprises less than 5% by weight, preferably less than 4% by weight, of BA, based on total fatty acids. Preferably, the nutritional composition comprises at least 0.5% by weight of butyric acid, based on total fatty acids, preferably at least 0.6% by weight, preferably at least 0.9% by weight, and more preferably at least 1.2% by weight of BA, based on total fatty acids.

[0177] In a preferred embodiment, the lipids in the nutritional composition comprise:

[0178] at least 10 wt.-% of PA based on total fatty acids, and at least 15 wt.-% of PA based on total PA is located in the sn-2 position of the triglyceride; and

[0179] 0.6 to 5 wt% SCFAs (ie the sum of BA and CA), based on total fatty acids.

[0180] Fatty acid composition

[0181] SFA refers to saturated fatty acids and / or acyl chains, MUFA refers to monounsaturated fatty acids and / or acyl chains, PUFA refers to polyunsaturated fatty acids and / or acyl chains with two or more unsaturated bonds; LC-PUFA refers to long-chain polyunsaturated fatty acids and / or acyl chains containing at least 20 carbon atoms and having two or more unsaturated bonds in the fatty acyl chain; medium-chain fatty acids (MCFA) refer to fatty acids and / or acyl chains with a chain length of 6, 8, or 10 carbon atoms. n3 or ω-3 PUFA refers to polyunsaturated fatty acids and / or acyl chains with two or more unsaturated bonds, with the unsaturated bond located at the third carbon atom from the methyl end of the fatty acyl chain; n6 or ω-6 PUFA refers to polyunsaturated fatty acids and / or acyl chains with two or more unsaturated bonds, with the unsaturated bond located at the sixth carbon atom from the methyl end of the fatty acyl chain.

[0182] In the context of the present invention, the weight percentages of fatty acids based on total fatty acids are calculated assuming that all fatty acids are free fatty acids, and therefore do not take into account whether the fatty acids are attached to a glycerol backbone.

[0183] DHA refers to docosahexaenoic acid and / or acyl chains (22:6n3); DPA refers to docosapentaenoic acid and / or acyl chains (22:5n3); n6 DPA refers to ω-6 docosapentaenoic acid and / or acyl chains (22:5n6). EPA refers to eicosapentaenoic acid and / or acyl chains (20:5n3); ARA refers to arachidonic acid and / or acyl chains (20:4n6). LA refers to linoleic acid and / or acyl chains (18:2n6); ALA refers to alpha-linolenic acid and / or acyl chains (18:3n3). PA refers to palmitic acid and / or acyl chains (C16:0). BA refers to butyric acid (C4:0). CA refers to caproic acid (C6:0).

[0184] LA refers to linoleic acid and / or acyl chains and is a precursor of n6 PUFA (18:2n6) and n6 LC-PUFA and is an essential fatty acid because it cannot be synthesized by the human body. The nutritional composition preferably comprises LA. LA is preferably present in a sufficient amount to promote healthy growth and development, but in an amount as low as possible to prevent a negative competitive effect on the formation of n3 PUFA and to prevent the n6 / n3 ratio from being too high. Therefore, the nutritional composition preferably comprises less than 20% by weight of LA based on total fatty acids, preferably 5% to 16% by weight, more preferably 10% to 14.5% by weight. Preferably, the nutritional composition comprises at least 5% by weight of LA based on total fatty acids, preferably at least 6% by weight of LA, more preferably at least 7% by weight of LA based on total fatty acids. Per 100 kcal, the nutritional composition preferably comprises 350 mg-1400 mg of LA.

[0185] ALA refers to alpha-linolenic acid and / or acyl chains and is a precursor of n3 PUFA (18:3n3) and n3 LC-PUFA and is an essential fatty acid because it cannot be synthesized by the human body. The nutritional composition preferably comprises ALA. Preferably, ALA is present in a sufficient amount to promote healthy growth and development of the infant. The nutritional composition preferably comprises at least 1.0 wt%, more preferably the nutritional composition comprises at least 1.5 wt%, even more preferably at least 2.0 wt% ALA based on total fatty acids. Preferably, the nutritional composition comprises less than 10 wt%, more preferably less than 5.0 wt% ALA based on total fatty acids.

[0186] Preferably, the nutritional composition comprises an LA / ALA weight ratio of 2 to 20, more preferably 3 to 16, even more preferably 4 to 14, most preferably 5 to 12.

[0187] The lipids in the nutritional composition preferably comprise 5 to 35 wt% PUFAs comprising LA and ALA in a LA / ALA weight ratio of 2 to 20, based on total fatty acids.

[0188] Preferably, the nutritional composition comprises n3 LC-PUFAs, such as EPA, DPA, and / or DHA, more preferably DHA. Because the conversion of ALA to DHA may be less efficient in infants, preferably both ALA and DHA are present in the nutritional composition. Preferably, the nutritional composition comprises at least 0.05 wt. %, preferably at least 0.1 wt. %, more preferably at least 0.2 wt. % DHA, based on total fatty acids. Preferably, the nutritional composition comprises no more than 2.0 wt. %, preferably no more than 1.0 wt. % DHA, based on total fatty acids.

[0189] The nutritional composition preferably includes ARA. Preferably, the nutritional composition includes at least 0.05% by weight based on total fatty acids, preferably at least 0.1% by weight, more preferably at least 0.2% by weight of ARA. Because n6 fatty acids (especially arachidonic acid (ARA)) offset n3 fatty acids (especially DHA), the nutritional composition preferably includes a relatively low amount of ARA. Preferably, the nutritional composition includes no more than 2.0% by weight based on total fatty acids, preferably no more than 1.0% by weight of ARA. Preferably, the weight ratio between DHA and ARA is 1:4 to 4:1, more preferably 1:2 to 2:1, more preferably 0.6 to 1.5.

[0190] Lipid globule size

[0191] Lipids are present in the form of lipid globules in milk formula particles. The lipid globules comprise a core and a surface.

[0192] The powdered nutritional composition thus comprises lipid globules. The lipids in the nutritional composition are in the form of lipid globules, and wherein:

[0193] a. The mode diameter of the lipid globules is at least 1.0 μm based on volume; and / or

[0194] b. At least 40% by volume of the lipid globules, based on the total lipid volume, have a diameter of 2 to 12 μm.

[0195] Lipid is typically present in the form of lipid globules in the milk formula particles of the nutritional composition. When the powdered nutritional composition is reconstituted in liquid form, these lipid globules are emulsified in an aqueous phase. Alternatively, when the nutritional composition is in powder form, the lipid globules are present in a milk formula powder, and the powder is suitable for reconstitution with water or another food-grade aqueous phase. The lipid globules comprise a core and a surface.

[0196] The core preferably comprises a plant lipid. The core preferably comprises at least 90% by weight triglycerides and more preferably consists essentially of triglycerides. All of the plant lipids present in the composition do not necessarily have to be contained in the core of the lipid globule, but preferably a majority of the plant lipids present in the composition, preferably greater than 50% by weight, more preferably greater than 70% by weight, even more preferably greater than 85% by weight, even more preferably greater than 95% by weight, most preferably greater than 98% by weight, are contained in the core of the lipid globule. In one embodiment, the core of the lipid globule comprises at least 40% by weight triglycerides of plant origin, more preferably at least 50% by weight, even more preferably at least 70% by weight triglycerides of plant origin, more preferably, the core of the lipid globule comprises at least 85% by weight, more preferably at least 95% by weight triglycerides of plant origin.

[0197] The mode diameter of the lipid globules in the milk formula particles of the nutritional composition is preferably at least 1.0 μm, more preferably at least 2.0 μm, and most preferably at least 3.0 μm, based on volume. Preferably, the mode diameter of the lipid globules is from 1.0 to 10 μm, more preferably from 2.0 to 8.0 μm, even more preferably from 3.0 to 7.0 μm, and most preferably from 3.0 to 6.0 μm, based on volume.

[0198] Alternatively or preferably in addition, the size distribution of the lipid globules is preferably in such a way that at least 45% by volume (volume %), preferably at least 55% by volume, even more preferably at least 65% by volume, and most preferably at least 75% by volume of the lipid globules have a diameter of 2 to 12 μm. In a more preferred embodiment, at least 45% by volume, preferably at least 55% by volume, more preferably at least 65% by volume, and most preferably at least 75% by volume of the lipid globules have a diameter of 2 to 10 μm. In an even more preferred embodiment, at least 45% by volume, more preferably at least 55% by volume, yet even more preferably at least 65% by volume, and most preferably at least 75% by volume of the lipid globules have a diameter of 4 to 10 μm. Preferably, less than 5% by volume of the lipid globules have a diameter higher than 12 μm.

[0199] Standard infant formula, follow-on formula or toddler formula typically has lipid globules with a mode diameter of about 0.3-0.5 μm on a volume basis and / or less than 45% by volume of the lipid globules have a diameter above 2 μm.

[0200] The volume percentage of lipid globules is based on the volume of total lipids. The mode diameter relates to the most abundant diameter based on the volume % of total lipids, or the peak in a graphical representation (diameter on the X-axis and volume % on the Y-axis).

[0201] The volume of lipid globules and their size distribution may be suitably determined, for example, by the method described in Michalski et al., 2001, Lait [Food Science] 81: 787-796, using a particle size analyzer such as the Mastersizer 2000 (Malvern Instruments, Malvern, UK).

[0202] phospholipids

[0203] The nutritional composition preferably comprises phospholipids, more preferably phospholipids derived from mammalian milk, even more preferably phospholipids derived from non-human mammalian milk. Phospholipids derived from non-human mammalian milk include phospholipids separated from milk lipids, cream lipids, butter serum lipids, butter serum lipids, beta serum lipids, serum lipids, casein lipids and / or buttermilk lipids. Buttermilk lipids are typically obtained during the manufacture of buttermilk. Butter serum lipids or beta serum lipids are typically obtained during the manufacture of anhydrous milk fat from cream or butter. Preferably, the phospholipids are obtained from dairy cream. The phospholipids are preferably derived from cow's milk, mare's milk, sheep's milk, goat's milk, buffalo's milk, horse's milk and camel's milk, most preferably cow's milk. Most preferably, a lipid extract isolated from cow's milk is used. A suitable source of phospholipids derived from non-human mammalian milk is the fraction isolable from milk called milk fat globule membrane (MFGM). Thus, in one embodiment the phospholipids used in the nutritional composition in the method or use according to the invention originate from or form part of milk fat globule membrane (MFGM) or are provided as MFGM, preferably bovine milk MFGM.

[0204] The nutritional composition preferably comprises 0.5 to 20 wt% phospholipids based on total lipids, preferably 0.5 to 10 wt% based on total lipids, even more preferably 0.75 to 8 wt%, even more preferably 1.2 to 8 wt%, and most preferably 1.35 to 5 wt% phospholipids.

[0205] In a preferred embodiment, the lipids in the nutritional composition are in the form of lipid globules, wherein:

[0206] a. The mode diameter of the lipid globules is at least 1.0 μm based on volume; and / or

[0207] b. at least 40% by volume, more preferably at least 45% by volume, of the lipid globules have a diameter of 2 μm to 12 μm, based on the total lipid volume,

[0208] And wherein the lipid globules are at least partially coated with phospholipids on the surface.

[0209] In a more preferred embodiment, the lipids in the nutritional composition are in the form of lipid globules, wherein:

[0210] a. The mode diameter of the lipid globules is at least 1.0 μm based on volume, and / or

[0211] b. at least 40% by volume, even more preferably at least 45% by volume of the lipid globules have a diameter of 2 to 12 μm,

[0212] and wherein the lipids comprise at least 0.5 wt% phospholipids based on total lipids.

[0213] "Coating" means that the outer surface layer of the lipid globules contains phospholipids, while the presence of phospholipids in the core of the lipid globules is much less. A suitable way to determine whether phospholipids are located on the surface of the lipid globules is confocal laser scanning microscopy or transmission electron microscopy; see, for example, Gallier et al. (A novel infant milk formula concept: Mimicking the human milk fat globule structure [New infant milk formula food concept: Simulating human milk fat globule structure], Colloids and Surfaces B: Biointerfaces [Colloids and surfaces B series: biological surface interface] 136 (2015) 329-339).

[0214] The nutritional composition preferably comprises glycerophospholipids. Examples of glycerophospholipids are phosphatidylcholine (PC), phosphatidylserine (PS), phosphatidylethanolamine (PE), phosphatidylinositol (PI) and phosphatidylglycerol (PG). Preferably, the nutritional composition comprises one or more of PC, PS, PI and PE, more preferably the nutritional composition comprises at least PC.

[0215] The nutritional composition preferably comprises sphingomyelin. Sphingomyelin has a phosphocholine or phosphoethanolamine molecule esterified to the 1-hydroxyl group of ceramide. They are classified as phospholipids and sphingolipids, but are not classified as glycerophospholipids or glycosphingolipids. Preferably, the nutritional composition comprises 0.05 wt % to 10 wt % of sphingomyelin based on the total lipids, more preferably 0.1 wt % to 5 wt % based on the total lipids, even more preferably 0.2 wt % to 2 wt % of sphingomyelin. Preferably, the nutritional composition comprises at least 5 wt % based on the total phospholipids, more preferably 5 wt % to 40 wt %, more preferably 10 wt % to 35 wt % based on the total phospholipids, even more preferably 15 wt % to 35 wt % of sphingomyelin.

[0216] The nutritional composition preferably comprises glycosphingolipids. Preferably, the nutritional composition comprises 0.1% to 10% by weight based on the total lipids, more preferably 0.5% to 5% by weight based on the total lipids, and even more preferably 2% to 4% by weight of glycosphingolipids. The term glycosphingolipids herein refers in particular to glycolipids having the amino alcohol sphingosine. The sphingosine backbone is O-linked to a charged head group such as an ethanolamine, serine, or choline backbone. The backbone is also amide-linked to a fatty acyl group. Glycosphingolipids are ceramides with one or more sugar residues linked to them by a β-glycosidic bond at the 1-hydroxy position, and include gangliosides. Preferably, the nutritional composition contains gangliosides, more preferably at least one ganglioside selected from the group consisting of GM3 and GD3.

[0217] The nutritional composition preferably comprises phospholipids derived from mammalian milk. Preferably, the nutritional composition comprises phospholipids and glycosphingolipids derived from mammalian milk. The nutritional composition preferably comprises phospholipids and optionally glycosphingolipids from the milk of mammals such as cows, mares, sheep, goats, buffaloes, horses and / or camels. More preferably, the nutritional composition comprises phospholipids and optionally glycosphingolipids from bovine milk.

[0218] The phospholipids derived from milk preferably include phospholipids separated from milk fat, cream lipids, butter serum lipids, butter serum lipids (β serum lipids), serum lipids, cheese lipids and / or buttermilk lipids. Buttermilk lipids are typically obtained during the manufacture of buttermilk. Butter serum lipids or β serum lipids are typically obtained during the manufacture of anhydrous milk fat from butter. Preferably, phospholipids and optionally glycosphingolipids are obtained from dairy cream. Examples of suitable commercially available sources of phospholipids from milk are BAEF, SM2, SM3 and SM4 powders from Corman, Salibra from Glanbia, Lipamin M20 from Lecico, Vivinal MFGM from Royal FrieslandCampina and LacProdan MFGM-10 or PL20 from Arla.

[0219] The use of phospholipids from milk fat advantageously includes the use of milk fat globule membranes that are more similar to those found in human milk. Thus, the combined use of milk-derived phospholipids and triglycerides derived from a mixture of plant lipids and mammalian milk fat enables the production of lipid globules coated with a coating that is more similar to human milk, while providing an optimal fatty acid composition.

[0220] Preferably, the phospholipids are derived from mammalian milk fat, more preferably bovine mammalian milk fat.Preferably, the phospholipids are derived from or form part of the milk fat globule membrane (MFGM), more preferably bovine MFGM.

[0221] Preferably, the nutritional composition comprises phospholipids and glycosphingolipids. In preferred embodiments, the weight ratio of phospholipids:glycosphingolipids is 2:1 to 12:1, more preferably 2:1 to 10:1 and even more preferably 2:1 to 5:1.

[0222] Methods for obtaining lipid globules of increased size and coated with phospholipids are disclosed in, for example, WO 2010 / 027258 and WO 2010 / 027259.

[0223] digestible carbohydrates

[0224] Powdered nutritional composition includes digestible carbohydrates. The digestible carbohydrates are contained in the milk formula particles. Digestible carbohydrates preferably provide 25% to 75% of the total calories of the nutritional composition. Preferably, digestible carbohydrates provide 40% to 60% of the total calories. Based on calorie meter, the nutritional composition preferably includes 5g to 20g digestible carbohydrates / 100kcal, more preferably 6g to 16g / 100kcal. When in liquid form (for example, as instant feeding liquid), the nutritional composition preferably includes 3g to 30g digestible carbohydrates / 100ml, more preferably 6g to 20g, even more preferably 7g to 10g / 100ml. Based on dry weight, the nutritional composition preferably includes 20% to 80% by weight, more preferably 40% to 65% by weight of digestible carbohydrates. In other words, when the nutritional composition is in powder form, digestible carbohydrates are preferably present in an amount of 20g-80g / 100g dry weight, more preferably 40g-65g / 100g dry weight.

[0225] Preferred digestible carbohydrate sources are one or more of lactose, glucose, sucrose, fructose, galactose, maltose, starch and maltodextrin. Lactose is the main digestible carbohydrate present in human milk. Lactose advantageously has a low glycemic index. The nutritional composition preferably comprises lactose. The nutritional composition preferably comprises digestible carbohydrates, wherein at least 35% by weight, more preferably at least 50% by weight, more preferably at least 75% by weight, even more preferably at least 90% by weight, and most preferably at least 95% by weight of the digestible carbohydrates are lactose. Based on dry weight, the nutritional composition preferably comprises at least 25% by weight of lactose, preferably at least 40% by weight of lactose.

[0226] protein

[0227] The nutritional composition comprises protein. Protein preferably provides 5% to 20% of the total calories. Preferably, the nutritional composition comprises protein that provides 6% to 12% of the total calories. Preferably, the nutritional composition comprises less than 3.5g protein / 100kcal, more preferably, the nutritional composition comprises 1.5g to 2.1g protein / 100kcal, even more preferably 1.6g to 2.0g protein / 100kcal. Low protein concentration is advantageously closer to human milk because human milk contains a lower amount of protein based on total calories compared to cow's milk. The protein concentration in the nutritional composition is determined by the sum of protein, peptides and free amino acids. Based on dry weight, the nutritional composition preferably comprises less than 12% by weight, more preferably 9.6% to 12% by weight, even more preferably 10% to 11% by weight of protein.

[0228] In other words, when the nutritional composition is in powder form, the protein is preferably present in an amount of 9-12 g / 100 g dry weight, more preferably 10-11 g / 100 g dry weight of the composition. Based on the ready-to-drink liquid product, the nutritional composition preferably comprises less than 1.5 g protein / 100 ml, more preferably 1.2 to 1.5 g / 100 ml, even more preferably 1.25 to 1.35 g / 100 ml.

[0229] The source of protein is preferably selected in such a way that the minimum requirements for the content of essential amino acids are met and satisfactory growth is ensured. Therefore, protein sources based on milk proteins (such as whey, casein and mixtures thereof), as well as proteins based on soy, potato or pea are preferred. In the case of using whey protein, the protein source is preferably based on acid whey or sweet whey, modified sweet whey, whey protein isolate or mixtures thereof. Preferably, the nutritional composition comprises at least 3% by weight of casein based on dry weight. Preferably, the casein is complete and / or non-hydrolyzed.

[0230] indigestible carbohydrates

[0231] In addition to the HMO particles, the nutritional composition preferably further comprises additional non-digestible oligosaccharides. Preferably, the powdered nutritional composition comprises non-digestible oligosaccharides having a degree of polymerization (DP) of 2 to 250, more preferably 3 to 60. In a preferred aspect, the non-digestible oligosaccharides are comprised in the milk formula particles of the powdered nutritional composition.

[0232] Preferably, the nutritional composition comprises as additional non-digestible carbohydrates fructooligosaccharides, galactooligosaccharides and / or galacturonic acid oligosaccharides, more preferably fructooligosaccharides and / or galactooligosaccharides, even more preferably galactooligosaccharides, most preferably transgalactooligosaccharides. In a preferred embodiment, the nutritional composition comprises a mixture of galactooligosaccharides and fructooligosaccharides, more preferably a mixture of transgalactooligosaccharides and fructooligosaccharides.

[0233] Preferably, the nutritional composition comprises 80 mg to 2 g of additional non-digestible oligosaccharides per 100 ml, more preferably 150 mg to 1.5 g / 100 ml, even more preferably 300 mg to 1 g / 100 ml. Based on dry weight, the nutritional composition preferably comprises 0.25 wt% to 20 wt%, more preferably 0.5 wt% to 10 wt%, even more preferably 1.5 wt% to 7.5 wt% of non-digestible oligosaccharides. In other words, when the nutritional composition is in powder form, the non-digestible oligosaccharides are preferably present in an amount of 0.25 g to 20 g / 100 g of the dry weight of the composition, more preferably 0.5 g to 10 g / 100 g of the dry weight of the composition, even more preferably 1.5 g to 8.5 g / 100 g of the dry weight of the composition.

[0234] Preferably, the infant formula of the present invention further comprises fructooligosaccharides (FOS). Fructooligosaccharides are non-digestible oligosaccharides (NDO) comprising a chain of beta-linked fructose units with a degree of polymerization (DP) or average DP of 2 to 250, more preferably 2 to 100, even more preferably 10 to 60. Fructooligosaccharides include inulin, fructan and / or mixed polyfructans. A particularly preferred fructooligosaccharide is inulin. Fructooligosaccharides suitable for use in the composition are also commercially available, for example HP (Orafti). Preferably, the average DP of the fructooligosaccharide is higher than 20.

[0235] Preferably, the infant formula of the present invention further comprises galacto-oligosaccharides (GOS), preferably galacto-oligosaccharides comprising β-galacto-oligosaccharides and / or α-galacto-oligosaccharides. The galacto-oligosaccharides are preferably β-galacto-oligosaccharides. In a particularly preferred embodiment, the infant formula of the present invention comprises β-galacto-oligosaccharides ([galactose] n-glucose; wherein n is an integer in the range of 2 to 60, i.e., 2, 3, 4, 5, 6, ...., 59, 60; preferably, n is selected from 2, 3, 4, 5, 6, 7, 8, 9 and 10, wherein the galactose units are mostly linked together via β bonds). β-galacto-oligosaccharides are also known as trans-galacto-oligosaccharides (TOS). β-galacto-oligosaccharides are sold, for example, under the trademark Vivinal™ (Borculo Domo Ingredients, Netherlands). Another suitable source is Bi2Munno (Classado). Preferably, the galacto-oligosaccharides comprise β1,3, β-1,4 and / or β-1,6 bonds. In a preferred embodiment, the galacto-oligosaccharide comprises at least 80% (more preferably at least 90%) of β-1,4 and β-1,6 linkages based on the total linkages. In another preferred embodiment, the galacto-oligosaccharide comprises at least 50% (more preferably at least 60%) of β-1,3 linkages based on the total linkages. Galacto-oligosaccharides, preferably β-galacto-oligosaccharides, are more stimulating to bifidobacteria. Preferably, the infant formula of the present invention comprises galacto-oligosaccharides, preferably β-galacto-oligosaccharides, with a degree of polymerization (DP) of 15, 2 to 10, preferably with an average DP in the range of 3 to 7. In another embodiment, the infant formula of the present invention comprises fructo-oligosaccharides and galacto-oligosaccharides (GOS), preferably the galacto-oligosaccharide comprises β-galacto-oligosaccharide. More preferably, the fructo-oligosaccharide is a long-chain fructo-oligosaccharide (lcFOS) with an average DP greater than 20. More preferably, the galacto-oligosaccharide is a short-chain galacto-oligosaccharide (scGOS) with an average DP in the range of 3 to 7. The weight ratio of short-chain galacto-oligosaccharides to long-chain fructo-oligosaccharides ranges from 100:1 to 1:10, preferably from 20:1 to 1:1, preferably from 7:1 to 10:1, especially about 9:1.

[0236] Because HMOs are short chain oligosaccharides, in embodiments the ratio of total non-digestible short chain oligosaccharides to total long chain oligosaccharides is from 100:1 to 1:10, preferably from 20:1 to 1:1, most preferably from 8:1 to 12:1, especially about 10:1.

[0237] As with all ingredients in nutritional compositions for infants, the exact amount of HMOs can be adjusted depending on the age of the infant to whom the composition is fed. In such embodiments, the range is specifically about 0.5-2.0 g / l HMOs for IMF, about 0.2-1.0 g / l for second stage formula, and about 0.1-0.5 g / l HMOs for toddler formula. Because the amount of 2'FL is preferably 40% to 100% based on total HMOs, the amount of 2'FL is preferably about 0.2-2.0 g / l in IMF, about 0.1-1.0 g / l in FOF, and about 0.05-0.5 g / l in YCF. In ungraded embodiments, the amount of HMOs is specifically the levels described above for IMF for all ages (thus, these values ​​for HMOs also apply to FOF and YCF).

[0238] Additional ingredients

[0239] In embodiments, additional ingredients may be added to the base powder, such as ingredients compatible with the lipid fraction, such as, in preferred embodiments, oil-soluble vitamins. Additionally, in embodiments, vitamins, minerals, and / or nucleotides may be added via dry mixing. Vitamins may be selected from the group consisting of vitamin C, any B vitamin, vitamin K1, and vitamin K2. Minerals may be selected from the group consisting of Fe, Zn, Mn, Cu, Se, I, Ca, Mg, Na, K, and P, as well as food-approved compounds containing these elements.

[0240] Application of nutritional compositions

[0241] The powdered nutritional composition of the present invention and its reconstituted, ready-to-drink liquid are suitable for achieving a beneficial effect in a subject, preferably a human subject, preferably an infant, toddler, and child.

[0242] Thus, the present invention also provides a powdered nutritional composition for promoting metabolic health, promoting the development of good body composition, preventing the development of obesity later in life, promoting balanced growth, promoting lean growth, promoting cognitive development, improving brain health, improving gut health, providing a beneficial prebiotic effect, enhancing immune cell function and promoting immune health, preventing infection or improving recovery from infection, stimulating intestinal barrier function / epithelial cell regulators to improve gut health, and reducing the risk of and / or improving recovery from gut health problems, the powdered nutritional composition comprising (i) dairy formula particles comprising lipid, protein, digestible carbohydrates, and (ii) HMO particles, wherein the nutritional composition is selected from infant formula, stage II formula, and growing-up milk, wherein the nutritional composition is not human milk, and wherein the lipids in the dairy formula particles are in the form of lipid globules, and

[0243] a. The mode diameter of the lipid globules is at least 1 μm based on volume, and / or

[0244] b. at least 40% by volume of the lipid globules have a diameter of 2 to 12 μm,

[0245] And wherein the HMO particle comprises at least 2'FL.

[0246] Therefore, the present invention also encompasses the powdered nutritional composition of the present invention and the reconstituted, ready-to-drink liquid thereof of the present invention for beneficially providing the health effects associated with providing HMOs and the health effects associated with providing a nutritional composition comprising large lipid globules.

[0247] For certain jurisdictions, the invention may also be expressed as a method for (therapeutic) promoting metabolic health, promoting the development of good body composition, preventing the development of obesity later in life, promoting balanced growth, promoting cognitive development, improving brain health, improving gut health, providing beneficial prebiotic effects, enhancing immune cell function and promoting immune health, preventing infection or improving recovery from infection, stimulating intestinal barrier function / epithelial cell regulators to improve gut health, and reducing the risk of and / or improving recovery from gut health problems.

[0248] For certain jurisdictions, the present invention may also be expressed as the use of (i) a dairy formula particle comprising lipid, protein, digestible carbohydrates and (ii) an HMO particle in the manufacture of a powdered nutritional composition (infant formula or second formula or growing-up milk) for promoting metabolic health, promoting the development of good body composition, preventing the development of obesity later in life, promoting balanced growth, promoting lean growth, promoting cognitive development, improving brain health, improving gut health, providing a beneficial prebiotic effect, enhancing immune cell function and improving immune health, preventing infection or improving recovery from infection, stimulating intestinal barrier function / epithelial cell regulators to improve gut health, and reducing the risk of and / or improving recovery from gut health problems, wherein the HMO comprises at least 2'FL, wherein the lipid in the dairy formula particle comprises lipid globules, and wherein

[0249] a. The volume-weighted mode diameter of the lipid globules is at least 1.0 μm, and / or

[0250] b. At least 40% by volume of the lipid globules have a diameter of 2 to 12 μm.

[0251] In other words, the present invention also relates to the use of the powdered nutritional composition according to the present invention for promoting metabolic health, promoting the development of a good body composition, preventing the development of obesity later in life, promoting balanced growth, promoting lean growth, promoting cognitive development, improving brain health, improving intestinal health, providing beneficial prebiotic effects, improving immune cell function and enhancing immune health, preventing infection or improving recovery from infection, stimulating intestinal barrier function / epithelial cell regulators to improve intestinal health, and reducing the risk of intestinal health problems and / or improving recovery from intestinal health problems.

[0252] To support the effective use of the nutritional composition as described above, reference is made to the following literature:

[0253] 1. Berger, B. et al., Linking Human Milk Oligosaccharides, Infant Fecal Community Types, and Later Risk To Require Antibiotics. mBio, 2020, 11(2).

[0254] 2. Berger, PK, et al. Human milk oligosaccharide 2'-fucosyllactose links feedings at 1 month to cognitive development at 24 months in infants of normal and overweight mothers. PLoS One, 2020, 15(2): e0228323.

[0255] 3. Bode, L., Human milk oligosaccharides: every baby needs a sugar mama. Glycobiology, 2012, 22(9): 1147-62.

[0256] 4. Donovan, SM and SS Comstock, Human Milk Oligosaccharides Influence Neonatal Mucosal and Systemic Immunity. Ann Nutr Metab, 2016, 69 Suppl 2: 42–51.

[0257] 5. Natividad, JM, et al., Blends of Human Milk Oligosaccharides Confer Intestinal Epithelial Barrier Protection in Vitro. Nutrients, 2020, 12(10).

[0258] 6. Newburg, DS, et al., Human Milk Oligosaccharides and Synthetic Galactosyloligosaccharides Contain 3'-, 4-, and 6'-Galactosyllactose and Attenuate Inflammation in Human T84, NCM-460, and H4 Cells and Intestinal Tissue Ex Vivo. J Nutr, 2016, 146(2): 358-67.

[0259] 7. Goehring, KC, et al., Similar to Those Who Are Breastfed, Infants Fed a Formula Containing 2'-Fucosyllactose Have Lower Inflammatory Cytokines in a Randomized Controlled Trial. J Nutr, 2016, 146(12): 2559-2566.

[0260] 8. Marriage, BJ, et al., Infants Fed a Lower Calorie Formula With 2'FL Show Growth and 2'FL Uptake Like Breast-Fed Infants. J Pediatr Gastroenterol Nutr, 2015, 61(6): 649-58.

[0261] 9. Puccio, G., et al., Effects of Infant Formula With Human Milk Oligosaccharides on Growth and Morbidity: A Randomized Multicenter Trial. J Pediatr Gastroenterol Nutr, 2017, 64(4): 624-631.

[0262] 10. Reverri, EJ, et al., Review of the Clinical Experiences of Feeding Infants Formula Containing the Human Milk Oligosaccharide 2'-Fucosyllactose. Nutrients, 2018, 10(10).

[0263] 11. Marcobal, A. et al., Consumption of human milk oligosaccharides by gut-related microbes. J Agric Food Chem, 2010, 58(9): 5334-40.

[0264] 12. Asakuma, S. et al., Physiology of consumption of human milkoligosaccharides by infant gut-associated bifidobacteria. J Biol Chem, 2011, 286(40): 34583-92.

[0265] 13. Yu, ZT, NNNanthakumar and DSNewburg, The Human Milk Oligosaccharide 2'-Fucosyllactose Quenches Campylobacter jejuni-Induced Inflammation in Human Epithelial Cells HEp-2 and HT-29 and in Mouse Intestinal Mucosa. J Nutr, 2016, 146(10): 1980-1990.

[0266] 14. Newburg, DS, et al., Innate protection conferred by fucosylated oligosaccharides of human milk against diarrhea in breastfed infants. Glycobiology, 2004, 14(3): 253-63.

[0267] 15. Ruiz-Palacios, GM, et al., Campylobacter jejuni binds intestinal H(O)antigen (Fuc alpha 1, 2Gal beta 1, 4GlcNAc), and fucosyloligosaccharides of human milk inhibit its binding and infection. J Biol Chem, 2003, 278(16): 14112-20.

[0268] 16. Bienenstock, J., et al., Fucosylated but not sialylated milkoligosaccharides diminish colon motor contractions. PLoS One, 2013, 8(10): e76236.

[0269] 17. Mezoff, EA, et al. The human milk oligosaccharide 2'-fucosyllactoseaugments the adaptive response to extensive intestinal. Am J Physiol Gastrointest Liver Physiol, 2016, 310(6): G427-38.

[0270] 18. Azagra-Boronat, I. et al., Oligosaccharides Modulate Rotavirus-Associated Dysbiosis and TLR Gene Expression in Neonatal Rats. Cells, 2019, 8(8).

[0271] 19. Azagra-Boronat, I. et al., Immunomodulatory and Prebiotic Effects of 2'-Fucosyllactose in Suckling Rats. Front Immunol, 2019, 10: 1773.

[0272] 20. Xiao, L. et al., The Combination of 2'-Fucosyllactose with Short-ChainGalacto-Oligosaccharides and Long-Chain Fructo-Oligosaccharides that EnhanceInfluenzaVaccineResponsesIsAssociatedwithMucosalImmuneRegulationinMice. J Nutr, 2019, 149(5): 856-869.

[0273] 21. Gallier S. et al., Natural and processed milk and oil body emulsions: Bioavailability, bioaccessibility and functionality. Food Structure 13, 2017, 13-23.

[0274] 22. Breij L. et al., An infant formula with large, milk phospholipid-coated lipid droplets containing a mixture of dairy and vegetable lipids supports adequate growth and is well tolerated in healthy, term infants. Am J Clin Nutr, 2019; 109(3): 586-596; and

[0275] The following pre-published patent applications:

[0276] WO 2010027258,

[0277] WO 2010027259,

[0278] WO 2011115490,

[0279] WO 2011115491,

[0280] WO 2012173485,

[0281] WO 2012173486,

[0282] WO 2013191542,

[0283] WO 2015065193,

[0284] WO 2016163881,

[0285] WO 2017064304, and

[0286] WO 2018104512.

[0287] method

[0288] The nutritional composition according to the present invention can be prepared by dry-mixing a base powder containing milk particles with HMOS particles.

[0289] The present invention encompasses a nutritional composition obtainable by dry mixing HMO particles, and optionally at least partially digestible carbohydrates and optionally non-digestible carbohydrates, and a base powder comprising particles of a milk formula comprising large lipid globules and at least partially protein and optionally at least partially digestible carbohydrates.

[0290] In an embodiment, the method for preparing the nutritional composition comprises the following steps:

[0291] a) preparing a base powder, wherein digestible carbohydrates are optionally included in the base powder, added as solids during a dry mixing step, or both, and

[0292] b) dry mixing said base powder comprising milk formula particles containing at least lipid globules and protein with HMO particles comprising at least 2'FL.

[0293] Additional ingredients which may be selected from the group of vitamins, minerals, digestible carbohydrates, and additional (non-digestible) oligosaccharides are dry mixed with the base powder and the HMO.

[0294] The present invention also encompasses products obtainable by the above methods.The present invention also encompasses products in the form of ready-to-drink liquids for reconstitution with water or other food grade aqueous liquids.

[0295] In a preferred embodiment, the amount of lipids in the nutritional composition is 10-30% by weight of the dry matter, the amount of carbohydrates is 40-70% by weight of the dry matter, and the amount of phospholipids is 0.5-3% by weight, based on the weight of the total fat. Even more preferably, the amount of lipids in the nutritional composition is 10-30% by weight of the dry matter, the amount of protein is 10-30% by weight of the dry matter, the amount of carbohydrates is 40-70% by weight of the dry matter, and the amount of phospholipids is 0.5-3% by weight, based on the weight of the total fat.

[0296] In an embodiment, the method according to the present invention comprises a process of preparing a base powder comprising at least fat droplets, protein and carbohydrates, and a subsequent step of adding HMO and optionally further dry ingredients by dry mixing with the base powder. In an embodiment, the base powder is prepared by: a) providing an aqueous phase having a dry matter content of 10% to 60% by weight (based on the total weight of the aqueous phase), comprising at least one protein component and optionally carbohydrates, b) providing a liquid lipid phase comprising at least one lipid, and c) mixing the lipid phase with the aqueous phase in a ratio of 5% to 50% by weight using a mixer to provide an oil-water emulsion, and d) drying the emulsion obtained in step c).

[0297] WO 2010027259, WO 2013135739, WO 2013135738 and WO 2016146496 disclose examples of the above-mentioned methods for preparing base powders, which can be used in the method of the present invention to obtain base powders and dry-mix with HMO particles.

[0298] The method essentially comprises the following steps: a) providing an aqueous mixture comprising lipids and comprising proteins, digestible carbohydrates and optionally non-digestible oligosaccharides, wherein the lipids comprise 50% to 100% by weight of vegetable lipids, based on the total lipids, and wherein 0.2% to 20% by weight, based on the total lipids, are phospholipids, and b) homogenizing the mixture in two steps, wherein in the first step preferably 5-100 bar, more preferably 30-100 bar and in the second step 5-50 bar, and c) preferably sterilizing the homogenized mixture, and d) preferably spray drying the sterilized mixture. In the context of the present invention, the base powder or dairy formula granules are preferably dry-blended with the HMO granules after these steps.

[0299] Alternatively, the process can be described as a two-step emulsification process by the following steps:

[0300] a) providing an aqueous phase having a dry matter content of 5 to 75 wt.-% (based on the total weight of the aqueous phase), which comprises at least one protein component, b) providing a liquid lipid phase comprising at least one lipid, and c) performing a first homogenization step by homogenizing the lipid phase to the aqueous phase in a ratio of 3 to 50% (w / w) so as to obtain a first lipid- and protein component-containing composition comprising lipid globules, wherein at least 10% by volume of the lipid globules have a diameter > 12 μm and / or wherein the volume-weighted mode diameter of the lipid globules is from 5 to 25 μm, d) performing a second homogenization step by homogenizing the first lipid- and protein component-containing composition obtained in step c) with a nebulizer, wherein the particle size of the lipid globules obtained in step c) is reduced so as to obtain a second lipid- and protein component-containing composition comprising lipid globules, wherein less than 10% by volume of the lipid globules have a diameter > 12 μm and / or wherein the volume-weighted mode diameter of the lipid globules is from 2.5 to 7 μm. In the context of the present invention, these steps are preferably followed by dry blending of the base powder with the HMO.

[0301] use

[0302] Another aspect of the present invention relates to the use of dairy formula particles for reducing powder segregation in a powdered nutritional composition comprising (i) dairy formula particles and (ii) HMO particles, wherein the dairy formula particles comprise digestible carbohydrates, lipids and proteins, and wherein the lipids in the dairy formula particles are in the form of lipid globules, and

[0303] a. The mode diameter of the lipid globules is at least 1 μm based on volume, and / or

[0304] b. At least 40% by volume of the lipid globules have a diameter of 2 to 12 μm, wherein the HMO particles comprise at least 2'fucosyllactose (2'FL).

[0305] Preferably, the milk formula particles and the HMO particles are of different sizes, more preferably they are different in Dx(10), Dx(50) and / or Dx(90).

[0306] Examples

[0307] Example 1

[0308] Material

[0309] Small blends were prepared by dry-blending a base powder (BP) according to the invention (prepared in a manner similar to Example 1B of WO 2010 / 027259, wherein the volume-weighted mode diameter of the fat globules was between 3 and 7 μm) with lactose (Royal FrieslandCampina, Veghel), a premix (a mixture of powdered vitamins and minerals), and 2'FL (GlyCare 2FL 9000, DSM). For reference, a standard infant milk base powder (BP, having essentially the same composition and a volume-weighted mode diameter of fat globules between 0.3 and 0.5 μm) was also mixed with the same ingredients and tested for segregation. The amounts of the materials used in the blends are shown in Table 1.

[0310] Table 1: Quantities of ingredients used for 2'FL

[0311]

[0312] method

[0313] For physical analysis, the segregation risk of different blends was evaluated. Segregation was evaluated using a Jenike & Johanson segregation tester using the method described in ASTM D6941-12. The goal of the fluidized segregation test is to allow the material in the test chamber to reach a fully fluidized / aerated state and then allow the powder to slowly degas (sediment). When the test is complete and all powder in the chamber has settled, samples can be collected. The powder column is divided into three sections, and each section (top, middle, bottom) can be subjected to segregation analysis.

[0314] Both the top and bottom samples as well as the original sample (before fluidization) were characterized with the aid of a Malvern Mastersizer 3000 with respect to particle size distribution (PSD).

[0315] Based on the PSD, three characteristic parameters of each sample were recorded: d10, d50 and d90. Then, the segregation potential (SP) was calculated as:

[0316]

[0317] where d is the three quantiles (d 10 d 50 or d 90 , both by volume). Lower SP values ​​indicate lower segregation potential. The subscripts bottom and top refer to separation completed after fluidization, while d0 refers to the percentile value before the powder enters the test chamber.

[0318] The test results are shown in Table 2. As can be seen from the table, the product of the present invention does not undergo segregation, which is due to the SP d10 、SP d50 、SP d90 The SP value is indicated.

[0319] Table 2: Segregation potential results

[0320]

[0321] Example 2

[0322] The particle size distribution of 2'-FL particles (DSM), a reference infant milk based powder with small lipid globules (Reference) and a powder according to the invention with large lipid globules (Invention) was determined (Table 3).

[0323] The particle size distribution was measured using laser diffraction (Malvern Mastersizer 3000) equipped with a dry dispersion device (Aero S) operating at a dispersion pressure of 1 bar. The optical characteristics used for the data evaluation were 1.52 / 0.1 and non-spherical particle types were used.

[0324] Furthermore, using the particle size distribution values, the Euclidean differences between the powder according to the invention and the 2'-FL particles, and between the reference powder and the 2'-FL particles, were determined according to the following mathematical formula (Table 4):

[0325] (I)

[0326]

[0327] The Euclidean difference indicates how similar two distributions are by using the mathematical expression (Euclidean distance). The larger the value, the more different the distributions are.

[0328] The particle size distribution of the powder according to the invention is significantly larger; the Dx(10) to Dx(90) distribution of the powder according to the invention is 355 μm, compared to the reference powder product, which has a distribution range of 153 μm. The Dx(50) of the powder according to the invention is also more than twice the size of the Dx(50) of the reference powder.

[0329] The Euclidian difference values ​​of the milk formula powder according to the invention and 2'-FL were found to be significantly higher than those of the reference powder and 2'-FL. The higher Euclidian difference values ​​of the milk formula powder according to the invention and 2'-FL show that the two powders are very different in size.

[0330] Despite the differences between the milk formula particles and the HMO particles according to the invention, the latter combination advantageously does not segregate.

[0331] Table 3: Quantiles of powder particle size distribution

[0332]

[0333] Table 4: Euclidean difference of combinations of powder and 2'-FL

[0334] combination Euclidean difference The present invention + 2-FL 0.329 Reference +2-FL 0.200

Claims

1. A powdered nutritional composition comprising (i) milk formula particles comprising lipid, protein, digestible carbohydrates, and (ii) human milk oligosaccharide (HMO) particles, wherein the nutritional composition is selected from the group consisting of infant formula, follow-up formula, and growing-up milk, wherein the nutritional composition is not human milk, and wherein the lipid in the milk formula particles is in the form of lipid globules, and a. The mode diameter of the lipid globules is at least 1 μm based on volume, and / or b. at least 40% by volume of these lipid globules have a diameter of 2 to 12 μm, And wherein the HMO particles comprise at least 2'fucosyllactose (2'FL).

2. The nutritional composition according to claim 1, wherein the powder particle size distribution of the milk formula particles comprises a Dx(10) of at least 60 μm and / or a Dx(50) of at least 200 μm and / or a Dx(90) of at least 400 μm.

3. Nutritional composition according to claims 1 and 2, wherein the powder particle size distribution of the HMO particles comprises a Dx(10) of at least 5 μm and / or a Dx(50) of at least 40 μm and / or a Dx(90) of at most 315 μm.

4. The nutritional composition according to the preceding claim, wherein the (i) milk formula particles and the (ii) HMO particles have a Euclidian difference greater than 0.

2.

5. Nutritional composition according to the preceding claim, wherein the difference between the Dx(20) of the milk formula particles and the Dx(80) of the HMO particles is at least 10 μm.

6. The nutritional composition according to any one of claims 1 to 5, wherein the lipid globules comprise a coating comprising phospholipids and / or wherein the amount of phospholipids is 0.5-20% by weight of the total lipid content.

7. Nutritional composition according to claim 6, wherein the phospholipids originate from milk fat globule membrane (MFGM) or are provided as MFGM, preferably bovine milk MFGM.

8. The nutritional composition according to claims 1 to 7, wherein i) the lipids comprise linoleic acid and α-linolenic acid in a weight ratio of 2 to 20, and / or ii) the lipids comprise at least 10 wt.-% palmitic acid, based on the total lipids, and at least 15 wt.-% of this palmitic acid, based on the total palmitic acid, is esterified to the sn-2 position of the triglyceride.

9. Nutritional composition according to claims 1 to 8, wherein the (ii) HMO particles are present in an amount of 0.1-2 wt.-%, preferably 0.3-1 wt.-%, based on the weight of dry matter.

10. Nutritional composition according to claims 1 to 9, wherein the lipid contains both vegetable fat and milk fat, preferably in a weight ratio of 30:70 to 90:

10.

11. The nutritional composition according to claims 1 to 10, wherein the amount of lipids is 10-30% by weight of the dry matter, the amount of proteins is 9.6-12% by weight of the dry matter, the amount of carbohydrates is 40-70% by weight of the dry matter, and the amount of phospholipids is 0.5-3% by weight, based on the weight of the total fat.

12. The nutritional composition according to claims 1 to 11, wherein the HMOs comprise 2'FL and at least one selected from the group consisting of lacto-N-neotetraose (LNnT), p-lactose-N-neohexaose (p-LNnH), sialic acid, 3' sialyllactose (3'SL) and 6' sialyllactose (6'SL), 3' fucosyllactose (3-FL), difucosyllactose (DFL), lacto-N-fucopentaose (LNFP, such as lacto-N-fucopentaose I, lacto-N-fucopentaose II), lacto-N-fucopentaose (LNFP ... Lactose II, lactose-N-fucopentaose III, lactose-N-fucopentaose V), lactose-N-fucohexaose, lactose-N-difucohexaose (LNDFH, such as lactose-N-difucohexaose I and lactose-N-difucohexaose II), sialic acid lactose-N-tetraose (LSTa), sialic acid lactose-N-tetraose b (LSTb), sialic acid lactose-N-tetraose c (LSTc), disialyl lactose-N-tetraose (DSLNT), lactose-N-neodifucohexaose (LNnDFH [00145] In some embodiments, the present invention relates to a fucosyllactose-N-hexaose, a fucosyllactose-N-neohexa ...

13. Nutritional composition according to claims 1 to 12, further comprising additional non-digestible carbohydrates, preferably one or more from the group of FOS and GOS carbohydrates.

14. Nutritional composition according to claims 1 to 13, obtainable by dry mixing HMO particles, and optionally at least part of the digestible carbohydrates and optionally the non-digestible carbohydrates, and a base powder comprising large lipid globules and at least part of the protein and optionally at least part of the digestible carbohydrates.

15. Nutritional composition according to claim 14, wherein the base powder is obtainable by metering the lipid into an aqueous phase comprising protein and optionally part of the digestible carbohydrates and at least part of the phospholipids, mixing the combined aqueous and lipid phases to obtain an emulsion, and subsequently drying the emulsion, preferably in a spray dryer.

16. A method for preparing a nutritional composition according to any one of claims 1 to 15, comprising the following steps: a) preparing a base powder, wherein the digestible carbohydrates are optionally included in the base powder, added as solids in a dry mixing step, or both, and b) dry-mixing said base powder comprising at least the lipid globules and protein with the HMO particles comprising at least 2'FL.

17. The method according to claim 16, wherein the base powder is prepared by: a) providing an aqueous phase having a dry matter content of 10% to 60% by weight (based on the total weight of the aqueous phase), comprising at least one protein component, b) providing a liquid lipid phase comprising at least one lipid, and c) mixing the lipid phase with the aqueous phase in a ratio of 5% to 50% by weight using a mixer to provide an oil-water emulsion, and d) drying the emulsion obtained in step c).

18. Process according to claims 16 and 17, wherein additional ingredients selected from the group of vitamins, minerals, digestible carbohydrates, and additional (non-digestible) oligosaccharides are dry-mixed with the base powder and the HMOs.

19. A product obtainable by a process according to any one of claims 16 to 18.

20. The nutritional composition according to claims 1 to 15 and 19, wherein the powdered nutritional composition is reconstituted with water or other food grade aqueous liquid to form a ready-to-drink liquid.

21. The nutritional composition of claims 1 to 15, 19 and 20 for use in promoting metabolic health, promoting the development of good body composition, preventing the development of obesity later in life, promoting balanced growth, promoting lean growth, promoting cognitive development, improving brain health, improving gut health, providing a beneficial prebiotic effect, enhancing immune cell function and improving immune health, preventing infection or improving recovery from infection, stimulating intestinal barrier function / epithelial cell regulators to improve gut health, and reducing the risk of and / or improving recovery from gut health problems.

22. Use of milk formula particles for reducing powder segregation in a powdered nutritional composition, the nutritional composition comprising (i) milk formula particles comprising lipid, protein, digestible carbohydrates, and (ii) HMO particles, wherein the nutritional composition is selected from infant formula, follow-up formula and growing-up milk, wherein the nutritional composition is not human milk, wherein the lipid in the milk formula particles is in the form of lipid globules, and a. The mode diameter of the lipid globules is at least 1 μm based on volume, and / or b. at least 40% by volume of these lipid globules have a diameter of 2 to 12 μm, And wherein the HMO particles comprise at least 2'fucosyllactose (2'FL).

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