Infant formula for feeding infants who receive infant formula and breast milk

Abstract

FIELD: infant formulas.SUBSTANCE: infant formulas suitable for feeding infants who receive both infant formula and breast milk. Infant formula for feeding infants on mixed feeding, who receive both infant formula and breast milk, contains 2' -fucosyllactose (2' -FL) and 3-fucosyllactose (3-FL) in a mass ratio of 2' -FL : 3-FL not less than 2.5:1. In this case, the infant formula contains 3-FL in a concentration ranging from 50 µg / ml to 240 µg / ml, or ranging from 37 mg / 100 g dry weight to 180 mg / 100 g dry weight, or ranging from 7 mg / 100 kcal to 36 mg / 100 kcal, and 2' -FL in a concentration ranging from 500 μg / ml to 1500 μg / ml, or from 375 mg / 100 g dry weight to 1125 mg / 100 g dry weight, or from 75 mg / 100 kcal to 225 mg / 100 kcal. Non-therapeutic methods of providing nutrition to an infant include feeding the infant with both the above-mentioned infant formula and breast milk. The age of the infant ranges from 0 to 24 months.EFFECT: providing nutrition to infants on mixed feeding.19 cl, 2 tbl, 2 ex

Description

Field of technology to which the invention relates

[0001] The present invention relates to infant formulas suitable for feeding infants who receive both infant formula and breast milk, also known as mixed-fed infants.Background of the invention

[0002] Human milk is considered the gold standard of infant nutrition due to its unique and unrivaled combination of nutritional and functional components. Therefore, the World Health Organization (WHO) and other organizations recommend exclusively breastfeeding infants up to 6 months of age. When a mother is unable to breastfeed her child or chooses not to, infant formula (IF), developed based on the composition of mature human milk, is recognized as the best alternative to breast milk. Research aimed at improving the quality of infant formula is not necessarily aimed at mimicking the exact composition of human milk, but rather at achieving the functional effects observed in infants, which go beyond nutritional benefits.

[0003] Despite the WHO recommendation for exclusive breastfeeding of infants up to 6 months of age, mixed feeding is common worldwide, meaning infants receive both formula and breast milk from birth until 6 months of age. In China, for example, it is common hospital practice for newborns to be given formula first, and only later, i.e., one to three months after birth, do they begin to receive breast milk from their mother. In many European countries, infants often begin exclusively breastfeeding and are then introduced to formula after a couple of months, for example, when maternity leave ends and the mother has to return to work, and infants are left in daycare during the day.

[0004] Human milk contains several bioactive factors that are beneficial for the relatively immature immune system of infants. These components are divided into two distinct groups based on their protective role or their ability to promote maturation. Human milk oligosaccharides (HMOs) are believed to play a role in both protection and maturation. In an effort to improve infant formula and develop a more optimal composition to maximize the beneficial effects of human milk, significant attention has been paid to HMOs.

[0005] Many of the HMO structures discovered to date and described by Urashima et al. (Trends in Glycoscience and Glycotechnolology, 2018, 30; 172, SE51-SE65) are based on lactose and lactosamine or lacto-N-biose, or both, and their polymers, which can be further linked to either fucose or sialic acid, or both. These structures provide high chemical variability and protection from degradation and absorption, allowing most HMOs to escape digestion and metabolization in the proximal intestine and reach the distal intestine undigested, thereby exerting a prebiotic effect on specific bacterial populations, strengthening the intestinal barrier, and protecting against enteropathogenic infections. OGMs are present in breast milk in relatively high proportions (5-20 g / l).The most abundant OSM is 2'-fucosyllactose (2'-FL), which accounts for ~20% of the total oligosaccharides in human milk secretory cells. In vitro and in vivo studies using 2'-FL have demonstrated their immunomodulatory effects, which include promoting anti-inflammatory activity (HE et al. Gut 2016; 65:33–46) and inhibiting pathogen colonization (Ruiz-Palacios et al. J Biol Chem 2003; 278:141–1220).

[0006] Slupski concluded that milk maturation is not a random process (chapter in the book by Donovan et al. (eds.) on the topic “Human Milk: Composition, Clinical Benefits and Future Opportunities”, Nestlé Nutr Inst Workshop Ser 2019, 90:179-190). Slupski noted that the composition of human milk is carefully controlled by the mammary gland, which is guided by maternal genetics, and constantly changes to meet the nutritional needs of the newborn and facilitate the direction of microbial succession during the period of exclusive milk feeding, and possibly beyond. Furthermore, microbial and fecal metabolic profiles have been found to be more similar between formula-fed infants than between breastfed infants (HE et al., mSystems 2016; 1:e00128-16; O'Sullivan et al., J Proteome Res 2013; 12:2833-2845).It has been suggested that this may be due to differences in milk composition between breastfeeding mothers and to changes in milk composition during lactation, while the composition of infant formula does not change. Austin et al., Nutrients 2016, 8, 346; doi: 10:3390 / nu8060346, reports temporal changes in the content of 10 oligosaccharides in the milk of urban Chinese mothers.

[0007] WO 2019 / 110800 discloses spray-dried powders comprising a mixture of structurally distinct human milk oligosaccharides, methods for producing said spray-dried powder, its use in the manufacture of nutritional formulations, and nutritional formulations containing the spray-dried powder. This disclosure justifies the supplementation of nutritional formulations with a combination of different HMOs and is directly related to infant formulas. The structurally distinct HMOs in this mixture can be selected from the group consisting of 2'-FL, 3-FL, LNT, LNnT, LNFPI, 3'-SL, 6'-SL, LST-A, LST-b, LST-c, and DSLNT (p. 7, lines 8-10).

[0008] A product consisting of five breast milk oligosaccharides - 2'-fucosyllactose (2'-FL), 3-fucosyllactose (3-FL), lacto-N-tetraose (LNT), 3'-sialyllactose (3'-SL) and 6'-sialyllactose (6'-SL), is produced by Jennewein Biotechnologie GmbH under the name 5HMO-Mix. The essence of the invention

[0009] The invention is based on a study that analyzed the composition of breast milk from two groups of Chinese mothers. Group I exclusively breastfed (EBF), i.e., without supplementing with infant formula; Group II used mixed milk feeding (MMF), i.e., a combination of breastfeeding and infant formula.

[0010] The inventors found that there were systematic variations in the composition of the OGM between the two groups I and II. Although the content of 2'-fucosyllactose (2'-FL) did not differ significantly between groups I and II, it was found that the content of 3-fucosyllactose (3-FL) differed significantly and was [on average] approximately 92 μg / mL higher in group II (SMV) compared to group I (GV).

[0011] Thus, the inventors identified a need for a modified infant formula suitable for feeding infants receiving both infant formula and breast milk (mixed-fed infants) that would take into account and compensate for the differences observed between Group I (BF) mothers and Group II (SMF) mothers.

[0012] Accordingly, an infant formula suitable for feeding infants receiving both infant formula and human milk (mixed-fed infants) containing 2'-FL and 3-FL is proposed, which utilizes a defined mass ratio of these HMOs and specific quantities of both HMOs. Differences in HMO intake in mixed-fed infants compared to breastfed infants were taken into account and compensated for by introducing the required quantitative restrictions for the use of 2'-FL and 3-FL.

[0013] In addition to 2'-FL and 3-FL, it was also found that the level of 3'-sialyllactose (3'-SL) and 6'-sialyllactose (6'-SL) were significantly different between Groups II and I. It was found that the level of 3'-SL was [on average] about 30 μg / mL higher in Group II (SMW) compared with mothers in Group I (BF), and the level of 6'-SL was [on average] about 76 μg / mL higher in Group II (SMW) compared with mothers in Group I (BF).

[0014] Thus, according to the invention, an infant formula can be improved by including a certain amount of 3'-SL in a certain ratio to 2'-FL and / or by including a certain amount of 6'-SL in a certain ratio to 2'-FL. By introducing additional quantitative restrictions when using 3'-SL or 6'-SL, it is possible to further take into account and compensate for the differences in HMO consumption that are found in infants on a formula-fed diet compared to breastfed infants. The differences in HMO consumption that are found in infants on a formula-fed diet compared to breastfed infants are further taken into account and compensated for by introducing the required quantitative restrictions for both 3'-SL and 6'-SL. Detailed description of the invention

[0015] Thus, the present invention relates to infant formulas suitable for feeding infants receiving both infant formulas and breast milk (mixed-fed infants), containing a) 2'-fucosyllactose (2'-FL) and 3-fucosyllactose (3-FL) in a weight ratio of 2'-FL: 3-FL of at least 2.5:1, and b) 3-FL in a concentration of no more than 240 μg / ml and / or, and c) 2'-FL in a concentration of no less than 500 μg / ml.

[0016] The ingredients of the infant formula according to the invention may also be present in amounts based on dry weight. Therefore, the present invention thus relates to an infant formula suitable for feeding infants receiving both infant formula and breast milk (mixed-fed infants), comprising a) 2'-fucosyllactose (2'-FL) and 3-fucosyllactose (3-FL) in a weight ratio of 2'-FL: 3-FL of at least 2.5:1, and b) 3-FL in a concentration of no more than 180 mg / 100 g dry weight, and c) 2'-FL in a concentration of no more than 375 mg / 100 g dry weight.

[0017] The ingredients in the infant formula of the invention may also be provided in amounts based on calories. Accordingly, the present invention thus relates to an infant formula suitable for feeding infants receiving both infant formula and breast milk (mixed-fed infants), comprising a) 2'-fucosyllactose (2'-FL) and 3-fucosyllactose (3-FL) in a weight ratio of 2'-FL: 3-FL of at least 2.5:1, and b) 3-FL in a concentration of no more than 36 mg / 100 kcal, and c) 2'-FL in a concentration of no more than 75 mg / 100 kcal.

[0018] In one embodiment, the infant formula according to the invention preferably further comprises d) 3'-sialylactose (3'-SL) in a weight ratio of 2'-FL: 3'-SL of at least 11.2:1, and e) 3'-SL in a concentration of not higher than 100 μg / ml.

[0019] If the amounts specified are based on dry weight, the proposed infant formula preferably further comprises d) 3'-sialylactose (3'-SL) in a 2'-FL: 3'-SL weight ratio of at least 11.2:1, and e) 3'-SL in a concentration of not more than 75 mg / 100 g dry weight.

[0020] If the amounts stated are based on calories, the proposed infant formula preferably further comprisesd) 3'-sialylactose (3'-SL) in a 2'-FL:3'-SL weight ratio of at least 11.2:1, ande) 3'-SL in a concentration of not more than 15 mg / 100 kcal.

[0021] In another embodiment, the infant formula according to the invention preferably further comprises f) 6'-sialyllactose (6'-SL) in a weight ratio of 2'-FL: 6'-SL of at least 1.8:1, and g) 6'-SL in a concentration of not higher than 300 μg / ml.

[0022] If the amounts specified are based on dry weight, the proposed infant formula preferably further comprisesf) 6'-sialyllactose (6'-SL) in a weight ratio of 2'-FL : 6'-SL of at least 1.8:1, andg) 6'-SL in a concentration of not more than 225 mg / 100 g dry weight.

[0023] If the amounts stated are based on calories, the proposed infant formula preferably further comprisesf) 6'-sialyllactose (6'-SL) in a 2'-FL:6'-SL weight ratio of at least 1.8:1, andg) 6'-SL in a concentration of not more than 45 mg / 100 kcal.

[0024] In a preferred embodiment, the infant formula according to the invention further comprises d) 3'-sialylactose (3'-SL) in a 2'-FL: 3'-SL weight ratio of at least 11.2:1, and e) 3'-SL in a concentration of no more than 100 μg / ml, and f) 6'-sialyllactose (6'-SL) in a 2'-FL: 6'-SL weight ratio of no less than 1.8:1, and g) 6'-SL in a concentration of no more than 300 μg / ml.

[0025] If the specified amounts are based on dry weight, then in a preferred embodiment, the infant formula according to the invention further comprises d) 3'-sialylactose (3'-SL) in a 2'-FL : 3'-SL weight ratio of at least 11.2:1, and e) 3'-SL in a concentration of at most 75 mg / 100 g dry weight, and f) 6'-sialyllactose (6'-SL) in a 2'-FL : 6'-SL weight ratio of at least 1.8:1, and g) 6'-SL in a concentration of at most 225 mg / 100 g dry weight.

[0026] If the specified amounts are based on calories, then in a preferred embodiment, the infant formula according to the invention further comprises d) 3'-sialylactose (3'-SL) in a 2'-FL : 3'-SL weight ratio of at least 11.2:1, and e) 3'-SL in a concentration of at most 15 mg / 100 kcal, and f) 6'-sialyllactose (6'-SL) in a 2'-FL : 6'-SL weight ratio of at least 1.8:1, and g) 6'-SL in a concentration of at most 45 mg / 100 kcal.

[0027] A preferred infant formula according to the invention contains 2'-FL in a concentration ranging from 500 μg / ml to 1500 μg / ml, preferably in a range from 750 μg / ml to 1250 μg / ml. If the specified amounts are based on dry weight, then a preferred infant formula according to the invention contains 2'-FL in a concentration ranging from 375 mg / 100 g dry weight to 1125 mg / 100 g dry weight, preferably in a range from 560 mg / 100 g dry weight to 940 mg / 100 g dry weight. When the amounts are based on calories, a preferred infant formula according to the invention contains 2'-FL in a concentration in the range of 75 mg / 100 kcal to 225 mg / 100 kcal, preferably in the range of 110 mg / 100 kcal to 190 mg / 100 kcal.

[0028] A preferred infant formula according to the invention contains 3-FL in a concentration ranging from 50 μg / ml to 240 μg / ml. If the stated amounts are based on dry weight, then the preferred infant formula according to the invention contains 3-FL in a concentration ranging from 37 mg / 100 g dry weight to 180 mg / 100 g dry weight. If the stated amounts are based on calories, then the preferred infant formula according to the invention contains 3-FL in a concentration ranging from 7 mg / 100 kcal to 36 mg / 100 kcal.

[0029] A preferred infant formula according to the invention contains 3'-SL in a concentration ranging from 10 μg / ml to 100 μg / ml, preferably in a range from 10 μg / ml to 75 μg / ml. If the said amounts are based on dry weight, the preferred infant formula according to the invention contains 3'-SL in a concentration ranging from 7 mg / 100 g dry weight to 75 mg / 100 g dry weight, preferably in a range from 7 mg / 100 g dry weight to 56 mg / 100 g dry weight. If the said amounts are based on calories, the preferred infant formula according to the invention contains 3'-SL in a concentration ranging from 1 mg / 100 kcal to 15 mg / 100 kcal, preferably in a range from 1 mg / 100 kcal to 12 mg / 100 kcal.

[0030] A preferred infant formula according to the invention contains 6'-SL in a concentration ranging from 50 μg / ml to 300 μg / ml, preferably in a range from 50 μg / ml to 250 μg / ml. If the specified amounts are based on dry weight, then a preferred infant formula according to the invention contains 6'-SL in a concentration ranging from 37 mg / 100 g dry weight to 225 mg / 100 g dry weight, preferably in a range from 37 mg / 100 g dry weight to 190 mg / 100 g dry weight. When the amounts are based on calories, a preferred infant formula according to the invention contains 6'-SFL in a concentration in the range of 7 mg / 100 kcal to 45 mg / 100 kcal, in the range of 7 mg / 100 kcal to 38 mg / 100 kcal.

[0031] In a further aspect, the invention also relates to a method for providing nutrition to an infant using the infant formula according to the invention, wherein feeding the infant includes both the infant formula and breastfeeding, and wherein the age of the infant is from 0 to 12 months, more preferably from 0 to 6 months, and particularly preferably from 0 to 4 months.

[0032] In some countries or territories, feeding an infant is considered therapeutic, in other countries or territories, feeding an infant is considered not therapeutic, therefore, the invention also relates to a non-therapeutic method of feeding an infant using the infant formula according to the invention, wherein feeding the infant includes both the infant formula and breastfeeding, and where the age of the infant is from 0 to 12 months, more preferably from 0 to 6 months, and particularly preferably from 0 to 4 months.

[0033] In another similar embodiment, the invention relates to the use of an infant formula according to the invention for providing nutrition to an infant, wherein the feeding of the infant includes both infant formula and breastfeeding, and wherein the age of the infant is from 0 to 12 months, more preferably from 0 to 6 months, and particularly preferably from 0 to 4 months.

[0034] Thus, according to the invention, an infant formula suitable for feeding infants receiving both infant formula and breast milk (mixed-fed infants) provides balanced nutrition and / or provides overall nutrition that is more similar to the nutrition of infants of the same age who are exclusively breastfed, and where the age of the infant is from 0 to 12 months, more preferably from 0 to 6 months, and more preferably from 0 to 4 months.

[0035] Similarly, according to the invention, an infant formula suitable for feeding infants receiving both infant formula and breast milk (mixed-fed infants) provides a balance of the observed differences between the two study groups and, thus, provides overall nutrition that is more similar to the nutrition of infants of the same age who are exclusively breastfed, and where the age of the infant is from 0 to 12 months, more preferably from 0 to 6 months, and more preferably from 0 to 4 months.

[0036] In other words, according to the invention, an infant formula suitable for feeding infants receiving both infant formula and human milk (mixed-fed infants) provides a balance between the observed systematic differences in the compositions of the HMO between the two study groups I and II, i.e. between exclusive breastfeeding (EBF) without supplementary feeding with infant formula, and mixed feeding (MF) and, thus, provides overall nutrition that is more similar to the nutrition of infants of the same age who are fed exclusively with breast milk, and where the age of the infant is from 0 to 12 months, more preferably from 0 to 6 months, and more preferably from 0 to 4 months.

[0037] In the context of the present invention, infants receiving both infant formula and breast milk preferably receive breast milk from mothers of the Asian race, or, in other words, infants who are breastfed with breast milk from a Asian mother. In general, it can be said that in the context of the present invention, infants receiving both infant formula and breast milk preferably receive breast milk from mothers of Chinese descent. Similarly, in the context of the present invention, infants receiving both infant formula and breast milk preferably belong to the Asian race or, more generally, are of Chinese descent. It is preferable that infants receiving both infant formula and breast milk belong to the Asian race and receive breast milk from mothers of the Asian race.More generally, it is preferable for infants receiving both formula and breast milk to be of Chinese descent and to receive breast milk from mothers of Chinese descent.

[0038] OGMs suitable for the preparation of infant formula according to the present invention are commercially available, for example, from Jennewein Biotechnologie GmbH. In other cases, it is entirely possible to obtain OGMs by isolation from suitable sources or by chemical synthesis.

[0039] In a preferred embodiment, an infant formula suitable for feeding infants receiving both infant formula and breast milk (mixed-fed infants) can be prepared by mixing the individual components of the OGM together with other known ingredients of the infant formula to obtain the quantitative composition of the infant formula according to the invention.

[0040] Each of the HMOs used according to the invention, i.e., 2'-FL, 3'-FL, 3'-SL, and 6'-SL, is known to inhibit one or more pathogens present in the human intestine, such as Campylobacter jejuni, Salmonella species, Streptococcici species, noroviruses, and rotaviruses. HMOs are also beneficial for the natural gut microbiome by promoting the growth of beneficial gut bacteria, such as Bifidobacteria species, Lactobacilli, and Bacteroides species. 2'-FL, 3-FL, and 6'-SL are also known to promote intestinal motility and the maturation of intestinal epithelial cells. Fucosylated and sialylated OGMs typically exhibit immunoregulatory functions and positively influence cytokine and inflammatory marker levels in non-breastfed and mixed-fed infants. 3SL and 6SL are also involved in infant brain development and play a role in cognitive and neural regulation.

[0041] Preferably, the proposed infant formula contains fructooligosaccharides (FOS). Fructooligosaccharides are indigestible oligosaccharides (NOS) consisting of a chain of beta-linked fructose units with a degree of polymerization (DP) or average DP of 2 to 250, preferably 2 to 100, and even more preferably 10 to 60. Fructooligosaccharide includes inulin, levan, and / or a mixed type of polyfructan. A particularly preferred fructooligosaccharide is inulin. Fructooligosaccharide suitable for use in the compositions can also be purchased from, for example, Raftiline®HP (Orafti). Preferably, the fructooligosaccharide has an average DP of over 20.

[0042] Preferably, the proposed infant formula comprises galactooligosaccharides (GOS), preferably, the galactooligosaccharides comprise beta-galactooligosaccharides and / or alpha-galactooligosaccharides. The galactooligosaccharides are preferably beta-galactooligosaccharides. In the most preferred embodiment, the proposed infant formula comprises beta-galactooligosaccharides ([galactose]n-glucose; where n is an integer from 2 to 60, i.e. 2, 3, 4, 5, 6, ...., 59, 60; the preferred n is selected from 2, 3, 4, 5, 6, 7, 8, 9 and 10), where the galactose units are in most cases linked to each other via a beta bond. Beta-galactooligosaccharides are also known as trans-galactooligosaccharides (TOS). Beta-galactooligosaccharides, for example, are sold under the brand name Vivinal(TM) (Borculo Domo Ingredients, Netherlands). Another suitable source is Bi2Munno (Classado).Preferably, the galactooligosaccharides comprise beta-1,3, beta-1,4 and / or beta-1,6 linkages. In a preferred embodiment, the galactooligosaccharides comprise at least 80% beta-1,4 and beta-1,6 linkages of the total number of linkages, preferably at least 90%. In another preferred embodiment, the galactooligosaccharides comprise at least 50% beta-1,3 linkages of the total number of linkages, preferably at least 60% of the total number of linkages.

[0043] Galactooligosaccharides, preferably beta-galactooligosaccharides, have a greater ability to stimulate bifidobacteria. The proposed infant formula preferably contains galactooligosaccharides, preferably beta-galactooligosaccharides, with a degree of polymerization (DP) of 2 to 10, preferably with an average DP of 3 to 7.

[0044] In a further embodiment, the proposed infant formula comprises fructooligosaccharides and galactooligosaccharides (GOS), preferred galactooligosaccharides comprise beta-galactooligosaccharides. More preferably, the fructooligosaccharides are long-chain fructooligosaccharides (lcFOS) with an average DP of over 20. More preferably, the galactooligosaccharides are short-chain galactooligosaccharides (scGOS) with an average DP in the range of 3 to 7. The weight ratio of short-chain galactooligosaccharides to long-chain fructooligosaccharides ranges from 100:1 to 1:10, preferably from 20:1 to 1:1, preferably is about 9:1.

[0045] The proposed infant formula preferably contains lipids, proteins, and digestible carbohydrates, wherein lipids provide 5 to 50% of the total calories, proteins provide 5 to 50% of the total calories, and digestible carbohydrates provide 15 to 90% of the total calories. Preferably, in the proposed infant formula, lipids provide 35 to 50% of the total calories, proteins provide 7.0 to 12.5% ​​of the total calories, and digestible carbohydrates provide 40 to 55% of the total calories. To calculate the percentage of total calories for proteins, it is necessary to take into account the total energy provided by proteins, peptides, and amino acids.Preferably, the lipid content is from 3 to 7 g lipid per 100 kcal, preferably from 4 to 6 g per 100 kcal, the protein content is from 1.6 to 4 g per 100 kcal, preferably from 1.7 to 2.5 g per 100 kcal, and the digestible carbohydrate content is from 5 to 20 g per 100 kcal, preferably from 8 to 15 g per 100 kcal of the nutritional composition. Preferably, the proposed infant formula contains lipids comprising from 4 to 6 g per 100 kcal, proteins comprising from 1.6 to 2.0 g per 100 kcal, more preferably from 1.7 to 1.9 g per 100 kcal, and digestible carbohydrates comprising from 8 to 15 g per 100 kcal of the nutritional composition.In one embodiment, the lipid content is from 3 to 7 g lipids per 100 kcal, preferably from 4 to 6 g per 100 kcal, the protein content is from 1.6 to 2.1 g per 100 kcal, preferably from 1.6 to 2.0 g per 100 kcal, and the digestible carbohydrates are from 5 to 20 g per 100 kcal, preferably from 8 to 15 g per 100 kcal of the infant formula, where it is preferred that the digestible carbohydrate component contains a lactose weight fraction of at least 60% of the total amount of digestible carbohydrates, more preferably at least 75% and even more preferably at least 90% of the total amount of digestible carbohydrates. The total amount of calories is determined by the sum of calories obtained from proteins, lipids, digestible carbohydrates and indigestible oligosaccharides.

[0046] The proposed infant formula preferably includes a digestible carbohydrate component. Preferred digestible carbohydrate components are lactose, glucose, sucrose, fructose, galactose, maltose, starch, and maltodextrin. Lactose is the main digestible carbohydrate in breast milk. The proposed infant formula preferably includes lactose. It is preferable that the proposed infant formula not contain large amounts of carbohydrates other than lactose. Compared with digestible carbohydrates such as maltodextrin, sucrose, glucose, maltose, and other digestible carbohydrates with a high glycemic index, lactose has a lower glycemic index and is therefore preferable.The proposed infant formula preferably contains digestible carbohydrates, wherein the mass fraction of lactose therein is at least 35%, preferably at least 50%, more preferably at least 60%, more preferably at least 75%, even more preferably at least 90%, particularly preferably at least 95%. Based on dry weight, the proposed infant formula preferably contains a mass fraction of at least 25% lactose, preferably at least 40%, and more preferably at least 50% lactose.

[0047] The composition of the proposed infant formula preferably includes at least one lipid selected from the group consisting of animal lipids (except human lipids) and plant lipids. It is preferable that the composition of the proposed infant formula includes plant lipids and at least one type of fat selected from the group consisting of fish oil, animal fat, algae oil, fungal oil and bacterial oil. The lipids in the proposed infant formula preferably make up from 3 to 7 g per 100 kcal of the nutritional composition, preferably the lipids make up from 4 to 6 g per 100 kcal. In liquid form, for example in the form of a ready-to-feed liquid, the infant formula preferably contains from 2.1 to 6.5 g of lipids per 100 ml, more preferably from 3.0 to 4.0 g per 100 ml. On a dry weight basis, the proposed infant formula preferably contains a lipid mass fraction of 2.5 to 40%, more preferably 19 to 30%.Preferably, the lipids comprise essential fatty acids: alpha-linolenic acid (ALA), linoleic acid (LA) and / or long-chain polyunsaturated fatty acids (LC-PUFA). LC-PUFA, LA and / or ALA can be used in the form of free fatty acids, in the form of triglycerides, in the form of diglycerides, in the form of monoglycerides, in the form of phospholipids, or as a mixture of one or more of the above. Preferably, the proposed infant formula contains at least one, preferably at least two, lipid sources selected from the group consisting of rapeseed oil (e.g., rapeseed oil, low-erucic rapeseed oil, and canola oil), high-oleic sunflower oil, high-oleic safflower oil, olive oil, seafood oils, microbial oils, coconut oil, and palm oil. The infant formula offered is not breast milk.

[0048] The composition of the proposed infant formula preferably includes proteins. The protein used in the infant formula is preferably selected from the group consisting of proteins from animals other than humans, preferably milk proteins, plant proteins, such as preferably soy protein and / or rice protein, and mixtures thereof. The proposed infant formula preferably contains casein and / or whey proteins, more preferably bovine whey proteins and / or bovine casein. Thus, in one embodiment, the protein in the proposed infant formula comprises a protein selected from the group consisting of whey proteins and casein, preferably whey proteins and casein, preferably whey proteins and / or casein from cow's milk. It is preferable that the protein contain a weight fraction of unbound amino acids, dipeptides, tripeptides or hydrolyzable protein of less than 5% of the total protein content.The proposed infant formula preferably contains casein and whey proteins in a casein: whey proteins weight ratio of 10:90 to 90:10, more preferably from 20:80 to 80:20, even more preferably from 35:65 to 55:45.

[0049] To meet the caloric needs of infants and toddlers, it is preferable for the caloric density of the infant formula to be between 45 and 200 kcal / 100 ml of fluid. It is preferable for the caloric density of the infant formula to be between 55 and 80 kcal / 100 ml of fluid, and even more preferably between 60 and 70 kcal / 100 ml of fluid. This caloric density ensures an optimal balance between water and calorie intake. The osmolarity of the proposed infant formula is preferably between 150 and 420 mOsmol / L, more preferably between 260 and 320 mOsmol / L. Low osmolarity is intended to further reduce gastrointestinal stress.

[0050] When the infant formula is in a ready-to-feed liquid form, the preferred volume fed per day is in the range of 80 to 2500 ml, more preferably 200 to 1200 ml per day. It is preferable that the number of feedings per day is from 1 to 10, preferably from 3 to 8. In one embodiment, the infant formula is given daily for at least 2 days, preferably for a period of at least 4 weeks, preferably for a period of at least 8 weeks, more preferably for a period of 25 at least 12 weeks, in liquid form, wherein the daily total feeding volume is from 200 ml to 1200 ml, and wherein the number of feedings per day is from 1 to 10.

[0051] The proposed infant formula generally contains a non-digestible oligosaccharide in a mass fraction of 2.5 to 20%, preferably 2.5 to 15%, even more preferably 3.0 to 10%, and particularly preferably 5.0 to 7.5%, based on the dry weight of the nutritional composition. Based on 100 ml of the proposed infant formula, the non-digestible oligosaccharide generally preferably contains a mass fraction of 0.35 to 2.5%, more preferably 0.35 to 2.0%, and even more preferably 0.4 to 1.5%, based on 100 ml of the nutritional composition. A smaller amount of non-digestible oligosaccharide will be less effective in improving the function of the intestinal microbiota, while too much will lead to side effects of bloating and abdominal discomfort.

[0052] The proposed infant formula may be in liquid form. The proposed infant formula may also be in the form of a dry product, preferably a powder, accompanied by instructions for mixing said dry product—preferably a powder—with a suitable liquid—preferably water. The infant formula used in accordance with the invention preferably contains other ingredients, such as vitamins, minerals, trace elements, and other micronutrients, to create a complete nutritional composition. Preferably, the infant formula contains vitamins, minerals, trace elements, and other micronutrients in accordance with international guidelines.

[0053] In a further aspect, the invention also relates to a non-therapeutic method for providing nutrition to an infant using an infant formula according to the invention, wherein feeding the infant includes both the infant formula and breastfeeding, and wherein the age of the infant is from 0 to 12 months, more preferably from 0 to 6 months, and particularly preferably from 0 to 4 months.

[0054] In a similar embodiment, the invention relates to a method for providing nutrition to an infant using an infant formula according to the invention, wherein feeding the infant includes both the infant formula and breastfeeding, and wherein the age of the infant is from 0 to 12 months, more preferably from 0 to 6 months, and particularly preferably from 0 to 4 months.

[0055] In another similar embodiment, the invention relates to the use of an infant formula according to the invention for providing nutrition to an infant, wherein the feeding of the infant includes both infant formula and breastfeeding, and wherein the age of the infant is from 0 to 12 months, more preferably from 0 to 6 months, and particularly preferably from 0 to 6 months. Examples Example 1

[0056] Breast milk samples were collected from 72 exclusively breastfeeding Chinese mothers and 65 Chinese mothers who used mixed feeding at 42 ± 2 days postpartum. All mothers were healthy, aged 20–40 years, and had given birth to a healthy infant.

[0057] Human milk samples were analyzed for NOS (3'-SL, 2'-FL, 3-FL, and 6'-SL) by liquid chromatography-tandem mass spectrometry based on the method described in Bao et al. 2013 (Bao, Y., Chen, C., & Newburg, D.S. (2013). Quantitative analysis of human milk neutral oligosaccharides was performed by high-performance liquid chromatography-tandem mass spectrometry. Analytical biochemistry, 433(1), 28-35.).

[0058] The results are shown in Table 1Table 1: Average amount of GM in milk of mothers exclusively breastfeeding (BF - group I) and of mothers using a combination of breastfeeding and formula feeding, i.e. mixed milk feeding (MMF - group II) 2'-FL (μg / ml) 3-FL (mcg / ml) 3'-SL (μg / ml) 6'-SL (μg / ml) GV Group I 997 423 84 309 SMV Group II 993 515* 114 385 Example 2

[0059] Infant formulas developed for infants aged 0-12 months are prepared using traditional infant formula production methods. Specific amounts of HMOs were added to the infant formula, suitable for feeding infants receiving both infant formula and breast milk (mixed-milk-fed infants). Table 2 shows the infant formula according to the invention.Table 2: Infant Formula Ingredients (unit) Infant formula for babies aged 0-12 months Proteins (g / 100 ml) 1,3 Fats (g / 100 ml) 3,4 Carbohydrates (g / 100 ml) 7,3 Lactose (g / 100 ml) 6,6 GOS+FOS (g / 100 ml) 0,7 Total nucleotide content (mg / 100 ml) 2,3 2'-FL (mg / 100 ml) 100 3-FL (mg / 100 ml) 20 3'-SL (mg / 100 ml) 5 6'-SL (mg / 100 ml) 25

Claims

1. Infant formula for feeding infants on mixed feeding, who receive both infant formula and breast milk, containing a) 2'-fucosyllactose (2'-FL) and 3-fucosyllactose (3-FL) in a mass ratio of 2'-FL: 3-FL of at least 2.5:1, and b) 3-FL in a concentration ranging from 50 μg / ml to 240 μg / ml, or ranging from 37 mg / 100 g dry weight to 180 mg / 100 g dry weight, or ranging from 7 mg / 100 kcal to 36 mg / 100 kcal, and c) 2'-FL in a concentration ranging from 500 μg / ml to 1500 μg / ml, or ranging from 375 mg / 100 g dry weight to 1125 mg / 100 g dry weight, or ranging from 75 mg / 100 kcal to 225 mg / 100 kcal.

2. Infant formula according to paragraph 1, additionally containing d) 3'-sialylactose (3'-SL) in a weight ratio of 2'-FL: 3'-SL of at least 11.2:1, and e) 3'-SL at a concentration of not more than 100 μg / ml, or not more than 75 mg / 100 g dry weight, or not more than 15 mg / 100 kcal.

3. Infant formula according to paragraph 1, additionally containing f) 6'-sialyllactose (6'-SL) in a 2'-FL:6'-SL weight ratio of at least 1.8:1, and g) 6'-SL at a concentration of not more than 300 μg / mg, or not more than 225 mg / 100 g dry weight, or not more than 45 mg / 100 kcal.

4. Infant formula according to paragraph 1, additionally containing d) 3'-sialylactose (3'-SL) in a weight ratio of 2'-FL: 3'-SL of at least 11.2:1, and e) 3'-SL at a concentration of not more than 100 μg / ml, or not more than 75 mg / 100 g dry weight, or not more than 15 mg / 100 kcal, and f) 6'-sialyllactose (6'-SL) in a 2'-FL:6'-SL weight ratio of at least 1.8:1, and g) 6'-SL at a concentration of not more than 300 μg / mg, or not more than 225 mg / 100 g dry weight, or not more than 45 mg / 100 kcal.

5. The infant formula according to any one of paragraphs 1-4, wherein the 2'-FL content varies in the range from 750 μg / ml to 1250 μg / ml, or in the range from 560 mg / 100 g dry weight to 940 mg / 100 g dry, or in the range from 110 mg / 100 kcal to 190 mg / 100 kcal.

6. The infant formula according to any one of claims 1 to 5, wherein the 3'-SL content ranges from 10 μg / ml to 100 μg / ml, preferably from 10 μg / ml to 75 μg / ml, or from 7 mg / 100 g dry weight to 75 mg / 100 g dry weight, preferably from 7 mg / 100 g dry weight to 56 mg / 100 g dry weight, or from 1 mg / 100 kcal to 15 mg / 100 kcal, preferably from 1 mg / 100 kcal to 12 mg / 100 kcal.

7. The infant formula according to any one of claims 1 to 6, wherein the 6'-SL content ranges from 50 μg / ml to 300 μg / ml, preferably from 50 μg / ml to 250 μg / ml; or from 37 mg / 100 g dry weight to 225 mg / 100 g dry weight, preferably from 37 mg / 100 g dry weight to 190 mg / 100 g dry weight; or from 7 mg / 100 kcal to 45 mg / 100 kcal, preferably from 7 mg / 100 kcal to 38 mg / 100 kcal.

8. An infant formula according to any one of paragraphs 1-7, additionally containing fructooligosaccharides, preferably fructooligosaccharides with an average degree of polymerization greater than 20.

9. The infant formula according to any one of claims 1 to 8, further comprising galactooligosaccharides, preferably galactooligosaccharides with an average degree of polymerization in the range from 3 to 7.

10. An infant formula according to any one of claims 1 to 9, containing fructooligosaccharides with an average degree of polymerization of over 20 and galactooligosaccharides with an average degree of polymerization in the range of 3 to 7, in a preferred weight ratio of fructooligosaccharides to galactooligosaccharides in the range of 10:1 to 1:

100.

11. An infant formula according to any one of claims 1 to 10, comprising lipids, proteins and digestible carbohydrates, wherein the lipids provide 3 to 7 g of lipids per 100 kcal, the proteins provide 1.6 to 4 g per 100 kcal, and the digestible carbohydrates provide 5 to 20 g per 100 kcal of the nutritional composition.

12. A non-therapeutic method of providing nutrition to an infant using infant formula according to any of the preceding paragraphs, wherein the feeding of the infant includes both infant formula and breastfeeding and wherein the age of the infant is between 0 and 24 months.

13. Non-therapeutic method according to paragraph 12, where the age of the infant is from 0 to 12 months.

14. Non-therapeutic method according to paragraph 12 or 13, where the age of the infant is from 0 to 6 months.

15. The use of an infant formula according to any of paragraphs 1-11 for providing nutrition to an infant, wherein the feeding of the infant includes both infant formula and breastfeeding, and wherein the age of the infant is from 0 to 24 months.

16. Use according to paragraph 15, where the age of the infant is from 0 to 12 months.

17. Use according to paragraph 15 or 16, where the age of the infant is from 0 to 6 months.

18. The non-therapeutic method according to paragraph 12, where the infant is fed with the breast milk of a mother of the Mongoloid race.

19. Use according to paragraph 15, where the infant is fed with breast milk of a mother of the Mongoloid race.