Infant nutrition containing hydrolyzed protein, ionized calcium and palmitic acid

Abstract

The present invention relates to a composition for a formula for infants or young children, the composition comprising a partially hydrolyzed protein, ionized calcium and an oil mixture comprising palmitic acid esterified to a triacylglycerol wherein the palmitic acid is esterified at the sn-2 position of the triacylglycerol, the esterified palmitic acid being in an amount of at least 20% by weight of the total palmitic acid. Furthermore, the present invention relates to an infant formula comprising said composition and the use of said composition or infant formula.

Description

[0001] This application is a divisional application of the original application with the application number 201580068747.3, the filing date of 17 December 2015, the priority date of 19 December 2014, and the invention title of "Infant nutrition containing hydrolysed proteins, ionic calcium and palmitic acid". TECHNICAL FIELD

[0002] The present invention relates to a composition for an infant or young child formula, said composition comprising partially hydrolysed proteins, ionic calcium and an oil mixture comprising palmitic acid esterified to triacylglycerols, wherein the palmitic acid comprises palmitic acid esterified in the sn-2 position of the triacylglycerols in an amount of at least 20 wt% of the total palmitic acid. Furthermore, the present invention relates to an infant formula comprising said composition and the use of said composition or infant formula. BACKGROUND

[0003] It is recommended that all infants continue to receive human milk as the sole source of nutrition until the age of 4-6 months, as human milk can provide infants with essential nutrients. However, in some cases breastfeeding is insufficient, or unsuccessful, or not advisable for medical reasons, or the mother does not choose breastfeeding at all or only breastfeeds for a few weeks. Infant formulas have been developed for these cases.

[0004] Research on the components of human milk has been ongoing for many years, and is still ongoing. However, research has shown that the nutrients contained in human milk differ from the nutrients used in commercially available infant formulas on the market today. For example, the type of lipid composition can differ greatly. The lipids present in human breast milk contain, for example, a high amount of palmitic acid esterified in the sn-2 (beta) position of the triacylglycerols, i.e. 68-72% of the palmitic acid in human milk is esterified in the sn-2 position. In infant formulas, vegetable oils are usually used as a source of lipids. The source of palmitic acid in infant formulas used today comprises a high amount, i.e. 80%, of palmitic acid esterified in the sn-1 (3) (alpha) position of the triacylglycerols.

[0005] This difference in oils and fats, in particular the difference in the regiospecific distribution of palmitic acid, causes differences in fat digestion in infants. It has been shown that feeding infants with infant formula comprising a mixture of oils containing palmitic acid and a high amount of said palmitic acid esterified in the sn-1 (3) position of triacylglycerols results in an increased calcium excretion in the stool compared to infants fed with human breast milk. Palmitic acid in the sn-1 and sn-3 position is very susceptible to cleavage and forms free fatty acids. Free palmitic acid can bind calcium in the intestine and form insoluble palmitic acid soaps. Excretion of these soaps in the stool can be part of the reason for the hard stools observed in some formula fed infants. Hard stools are a contributing factor to functional constipation in infants and young children.

[0006] Furthermore, calcium loss in a population such as infants can increase the risk of insufficient bone mineralization.

[0007] Some studies are known in which it was observed that infants fed with infant formula comprising a high relative proportion of sn-2 palmitate such as more than 66% of the total amount of palmitic acid as sn-2 palmitate (and less than 34% as sn-1 (3) palmitate) excreted significantly less calcium in the stool compared to infants fed with standard infant formula. In contrast, infants fed with infant formula having a more moderate content of sn-2 palmitate (about 44% of the total palmitic acid) did not show a significant reduction in stool calcium compared to infants fed with standard infant formula.

[0008] In Carnielli et al "The Intrinsic Fatty Acid Composition of Human Milk Fat and Its Changes With Feeding Pattern and Postpartum Period" Feeding premature newborn infants with palmitic acid in amounts and stereoisomeric position similar to that of human milk; effects on fat and mineral balance ", Am J Clin Nutr. May 1995 vol. 61 no. 5, page 1037-1042 (Carnielli et al, "Feeding premature Newborns with palmitic acid with the amount and stereochemical position similar to that of human milk: effects on fat and mineral balance", Am J Clin Nutr. May 1995 vol. 61 no. 5, page 1037-1042) it is disclosed that an infant formula with a sn-2 palmitate content close to human breast milk results in a reduced calcium excretion compared to infants fed with an infant formula with a high amount of sn-1 (3) palmitate.

[0009] In Carnielli et al "The Intrinsic Fatty Acid Composition of Human Milk Fat and Its Changes With Feeding Pattern and Postpartum Period" Structural position and amount of palmitic acid in infant formulas: effects on fat, fatty acid, and mineral balanceA study disclosed in J. Pediatr Gastroenterol Nutr. 1996, Dec;23(5):553-60 (Carnielli et al., "Structural position and amount of palmitic acid in infant formulas: effects on fat, fatty acid, and mineral balance", J. Pediatr Gastroenterol Nutr. 1996, Dec;23(5):553-60) showed that infants fed with an infant formula comprising 24% palmitic acid, of which 66% is esterified in the sn-2 position of triacylglycerols, would have significantly lower fecal calcium excretion compared to infants fed with an infant formula with intermediate and low amounts of sn-2 palmitate in total palmitic acid (24% palmitic acid of which 39% is esterified in the sn-2 position of triacylglycerols; and 20% palmitic acid of which 13% is esterified in the sn-2 position of triacylglycerols).

[0010] Furthermore, studies have demonstrated that an amount of 36% and less of total palmitic acid esterified in the sn-2 position of triacylglycerols and thus 64% and more of palmitic acid esterified in the sn-l(3) position of triacylglycerols in an infant formula will not result in a significant reduction of fecal calcium excretion.

[0011] Thus, palmitic acid and its regiospecific distribution (sn-2 versus sn-l(3)) are important for reducing calcium excretion in feces.

[0012] However, there is a need in the art for a composition for an infant or young child formula such that the amount of calcium excreted in feces is comparable to or even lower than the calcium level excreted by a human milk fed infant. SUMMARY

[0013] It is therefore an object of the present invention to provide a composition for an infant or young child formula and a human milk fortifier which can result in an amount of calcium excreted in feces which is as low as the calcium in feces when a human mother's breast milk is fed to an infant.

[0014] In particular, it is an object of the present invention to provide a composition which solves the problem of calcium excretion in the prior art described above and which further reduces the amount of calcium excreted by an infant fed with an infant formula.

[0015] Thus, one aspect of the present invention relates to a composition for an infant or young child formula, said composition comprising a partially hydrolyzed protein, ionic calcium and an oil mixture comprising palmitic acid esterified to triacylglycerols, wherein said palmitic acid comprises palmitic acid esterified in the sn-2 position of triacylglycerols in an amount of at least 20 wt.%.

[0016] Another aspect of the present invention is to provide an infant formula comprising the composition according to the present invention.

[0017] Yet another aspect of the present application relates to a composition or infant formula according to the present application for use in administering to an infant or young child for reducing calcium excretion in said infant or young child.

[0018] Still another aspect of the present application relates to a composition or infant formula according to the present application for use in administering to an infant or young child for increasing calcium homeostasis, increasing calcium absorption, increasing calcium retention, increasing calcium utilization and / or reducing palmitic acid soap formation.

[0019] In still another aspect, the present application relates to a composition or infant formula according to the present application for use in administering to an infant or young child for softening stools, preventing stool hardening and / or reducing the risk of stool hardening, preventing constipation and / or reducing the risk of constipation, improving feeding tolerance, reducing the frequency and duration of crying upset, and relieving digestive discomfort and colic.

[0020] In still another aspect, the present application relates to a composition or infant formula according to the present application for use in administering to an infant or young child for improving sleep duration, improving sleep quality and quantity, improving the quality of life of the infant and the parents, and reducing maternal anxiety.

[0021] In yet another aspect, the present application relates to a composition or infant formula according to the present application for use in administering to an infant or young child for increasing bone mineralization, increasing bone strength and / or increasing bone mineral density. DETAILED DESCRIPTION

[0022] Definitions: Before the present application is discussed, it is to be understood that the following definitions and abbreviations are herewith introduced for purposes of the disclosure herein:

[0023] As used herein, numerical ranges include each and every number and subset between the recited range values. Additionally, numerical ranges are inclusive of the recitations of values that are endpoints of the range. Numerical ranges are also inclusive of any values or sub-ranges within the indicated ranges. For example, a range from 1 to 10 is inclusive of the endpoints 1 and 10, as well as any number or subset between 1 and 10. All single feature or limitation values recited herein are inclusive of the corresponding values of any sub-range unless otherwise explicitly indicated or otherwise evident from context. For example, a recitation of a range from 1 to 10 is inclusive of a range from 1 to 8, from 3 to 7, from 1 to 9, from 3.6 to 4.6, from 3.5 to 9.9, etc. All single feature or limitation values recited herein are inclusive of the corresponding values of any sub-range unless otherwise explicitly indicated or otherwise evident from context. For example, a recitation of a range from 1 to 10 is inclusive of a range from 1 to 8, from 3 to 7, from 1 to 9, from 3.6 to 4.6, from 3.5 to 9.9, etc. All single feature or limitation values recited herein are inclusive of the corresponding values of any sub-range unless otherwise explicitly indicated or otherwise evident from context.

[0024] In the context of the present application, the term "weight ratio" (w / w) refers to the ratio between the weight of the compounds. For example, a mixture containing 60 g of whey and 40 g of casein has a weight ratio equal to 60:40, which is also equal to 3:2 or 1.5 (i.e. the result of 3 divided by 2). Similarly, with respect to a mixture containing 50 g of whey and 50 g of casein, the ratio by weight of whey and casein is 50:50, which is also equal to 1:1 or 1 (i.e. the result of 1 divided by 1).

[0025] The term "and / or", used in the context of "X and / or Y", should be interpreted as "X", "Y" or "X or Y".

[0026] As used in this specification, the words "comprises", "comprising", and similar words, are not to be interpreted in an exclusive or exhaustive sense. In other words, they are intended to mean "including, but not limited to".

[0027] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs.

[0028] In the context of the present application, the term "infant" means a child of an age of less than 12 months.

[0029] The term "young child" refers to a child of an age from 12 months to 4 years.

[0030] In the context of the present application, the infant can be any term infant or preterm infant. In one embodiment of the present application, the infant is selected from the group consisting of a preterm infant and a term infant.

[0031] The term "infant formula" as used in the context of the present application means a nutritional composition for infants during the first months of life, such as Codex Alimentarius , as defined in the Codex STAN 72-1981 (Codex Standard 72-1981) and Codex Alimentarius , as defined in the Codex STAN 72-1981 (Codex Standard 72-1981).

[0032] The term "follow-on formula" means a formula designed for use from 6 to 12 months of age. Typically, when a follow-on formula is administered, the infant is also administered other types of food, such as vegetable purees and / or fruit purees.

[0033] The term "growing-up milk" means a formula designed for use starting from one year of age. It is typically a milk-based beverage adapted to the particular nutritional needs of young children.

[0034] In the context of the present application, the term "composition for use in an infant or baby formula" refers to any formula for infants, which comprises all nutrients necessary to meet the standards defined in the Codex Alimentarius to be a formula for infants. Furthermore, the "composition for use in an infant or baby formula" can be a composition comprising nutrients, which can be mixed with other compositions of nutrients to prepare a formula, i.e. the "composition for use in an infant formula" can be added to a mixture intended to be used as an infant formula. Furthermore, the "composition for use in a formula" can be a supplement or fortifier for infant formula, baby formula, growing-up milk or human milk.

[0035] Oil mixture: In the context of the present application, the term "oil mixture" refers to a mixture of vegetable fat and vegetable oil, milk fat and / or animal fat, which comprises triacylglycerols as the main lipid source. The oil mixture can be a mixture of one or more vegetable oils and vegetable fats, for example selected from palm oil, palm kernel oil, esterified vegetable oils such as interesterified palm oil, animal fat and animal fat fractions. The oil mixture can also comprise other vegetable oils and vegetable fats suitable for use in infant nutrition. For example, the oil mixture can comprise one or more selected from the group consisting of soybean oil, coconut oil, rapeseed oil, canola oil, sunflower oil, safflower oil and milk fat.

[0036] In one aspect of the present application, the oil mixture used comprises palmitic acid, wherein the proportion of palmitic acid esterified in the sn-2 position of the triacylglycerols is at least 20% by weight of the total palmitic acid.

[0037] Palmitic acid: In the context of the present application, the term "palmitic acid" refers to the saturated fatty acid 16:0. The term "palmitate" can also be used for "palmitic acid" when esterified with glycerol, such as in triacylglycerols. Most of the palmitic acid in a lipid composition is esterified with triacylglycerols and can be located in the outer (sn-1 (3)) or inner (sn-2) position of the triacylglycerol. Palmitic acid is in the sn-1 (3) position of the triacylglycerol when it is esterified in the (outer) first or third position of the triacylglycerol. Such palmitic acid is referred to as sn-1 (3) palmitate in the context of the present application. Palmitic acid esterified in the inner position of the triacylglycerol is palmitic acid with the palmitic acid position in the sn-2 position of the triacylglycerol, and such palmitic acid is referred to as sn-2 palmitate in the context of the present application. The oil mixture according to the present application comprises triacylglycerols, and some of the triacylglycerols have esterified palmitic acid.

[0038] In the context of the present application, the term "amount of sn-2 palmitic acid" refers to the amount of beta-palmitic acid, calculated on the total amount of palmitic acid.

[0039] Similarly, the term "sn-1 (3) palmitic acid amount" refers to the amount of a- palmitic acid, calculated on the total amount of palmitic acid.

[0040] In one embodiment according to the application, the palmitic acid content of the fat blend is at least 8 wt%, such as at least 10 wt%, preferably at least 12 wt%, such as at least 15 wt%, even more preferably at least 18 wt%, of the total amount of fatty acids. [Jonathan will come back to this minimum amount]

[0041] In yet another embodiment according to the application, the palmitic acid content of the oil mixture is 8-30 wt%, such as a content of 10-26 wt%, preferably a content of 12-25 wt%. In particular, the oil mixture comprises 20-24 wt% palmitic acid.

[0042] In human milk, more than 98% of the fat is in the form of triacylglycerols containing saturated and unsaturated fatty acids. The main saturated fatty acid in human milk is palmitic acid, which accounts for 22-25% of the total amount of fatty acids.

[0043] In human milk, about 68-72% of the palmitic acid is esterified in the sn-2 position of the triacylglycerol.

[0044] In palm olein, which is a palm oil fraction widely used in infant formulae containing a high amount of palmitic acid, the amount of sn-1 (3) palmitate is 90-95%, so only about 5-10% of the palmitic acid is esterified in the sn-2 position of the triacylglycerol.

[0045] In most commercially available infant formulae, the majority (about 80-90%) of the palmitic acid present is esterified in the sn-1 (3) position of the triacylglycerol, i.e. in the form of sn-1 (3) palmitate.

[0046] However, it has been found that the position of the palmitic acid in the triacylglycerol has an impact on the absorption of minerals, e.g. the absorption of calcium, since free palmitic acid can form complexes with minerals. When palmitic acid is esterified in the sn-1 (3) position of the triacylglycerol, free palmitic acid is released from the triacylglycerol during digestion and forms insoluble complexes with minerals, such as calcium, which are present in sufficient amounts in the diet (this is called palmitic acid soap). These palmitic acid soaps are not absorbable and are therefore excreted in the form of faeces. The excretion of palmitic acid soaps leads to a loss of minerals and to poor nutrient absorption.

[0047] Palmitic acid soaps can be expressed in various ways, e.g. calcium soap, palmitic acid soap, calcium-fatty acid complex or insoluble complex. These terms can be used interchangeably, but are understood to be the same.

[0048] In contrast, when palmitic acid is esterified at the sn-2 position of triacylglycerols, the unsaturated fatty acids esterified at the sn-1 (3) position of triacylglycerols are released during digestion and are well absorbed, thus avoiding the formation of palmitic acid soaps. Furthermore, the sn-2 palmitate ester in the form of monacylglycerols is well absorbed. Therefore, if a large amount of palmitic acid is at the sn-1 (3) position of triacylglycerols, a large amount of calcium will be excreted in the feces. Studies have demonstrated that the use of oil mixtures comprising palmitic acid with a high amount of sn-2 palmitate ester, such as an amount similar to that in human milk, preferably greater than 65-70%, causes a reduction in calcium excretion compared to the use of oil mixtures with a smaller amount of sn-2 palmitate ester.

[0049] A high amount of sn-2 palmitate ester is considered to be an amount of sn-2 palmitate ester close to the amount in human milk, i.e. a high amount of sn-2 palmitate ester is considered to be in the range of 68-80% by weight of total palmitic acid, such as at least 65% by weight of total palmitic acid as sn-2 palmitate ester.

[0050] The inventors of the present application have surprisingly found that the combination of an oil mixture containing palmitic acid, a partially hydrolyzed protein and ionic calcium has a synergistic effect on calcium absorption when combined with sn-2 palmitate ester lipids. The inventors have found that when an oil mixture containing a moderate amount, for example about 20-60% by weight, and a high amount (65-80%) of sn-2 palmitate ester is combined with a partially hydrolyzed protein and ionic calcium, the amount of calcium excreted in the feces after digestion by an infant or young child is close to the amount excreted by an infant fed with human milk.

[0051] Therefore, another aspect of the present application is to provide a composition for an infant or young child formula, the composition comprising a partially hydrolyzed protein, ionic calcium and an oil mixture containing palmitic acid esterified into triacylglycerols, wherein the palmitic acid comprises palmitic acid esterified at the sn-2 position of palmitic acid in an amount of at least 20% by weight of total palmitic acid.

[0052] In one embodiment according to the present application, the oil mixture comprises sn-2 palmitate ester in an amount of 2-15% of the total fatty acids present in the oil mixture, and sn-1 (3) palmitate ester in an amount of 5-14% of the total fatty acids in the oil mixture.

[0053] In yet another embodiment of the present application, the oil mixture comprises palmitic acid, wherein the amount of palmitic acid comprises 20-80% by weight of sn-2 palmitate ester. In a preferred embodiment, the palmitic acid comprises sn-2 palmitate ester in an amount of 25-75% by weight, such as sn-2 palmitate ester in an amount of 30-70% by weight, preferably sn-2 palmitate ester in an amount of 35-65% by weight.

[0054] Oil mixtures comprising specific amounts of sn-2 palmitate can be prepared by mixing different vegetable oils or by mixing vegetable oils with milk fat. An example of an oil mixture can be a mixture of cow milk fat with one or more vegetable oils such as sn-2 palmitate, palm oil, coconut oil, soybean oil, high oleic safflower oil and sunflower oil. These fats and oils can be blended in ratios sufficient to provide a fatty acid profile similar to that found in human milk.

[0055] A commercially available composition sold by Lipid Nutrition is Betapol ™ B-55, which is a triglyceride mixture derived from vegetable oil in which at least 54% of the palmitic acid is in the sn-2 position of the glycerol molecule. In one embodiment, the oil mixture present in the composition according to the application is Betapol ™ Mixtures of B-55 with other vegetable oils. Those skilled in the art will appreciate that the percentage of sn-2 palmitate used in the formula, as well as the total amount of palmitate, can vary and different sn-2 palmitate oils can be used without departing from the spirit and scope of the application.

[0056] In another embodiment of the application, the oil mixture further comprises stearic acid, i.e. triacylglycerols with stearic acid attached to them via an ester bond.

[0057] Protein: In one aspect of the application, the composition comprises partially hydrolyzed protein.

[0058] The inventors of the present application surprisingly found that hydrolyzed protein has a positive effect on calcium absorption and that even if the palmitic acid is not all located in the sn-2 position, hydrolyzed protein in combination with palmitic acid reduces the formation of palmitic acid soaps and thus reduces calcium excretion. Furthermore, the inventors found that ionic calcium in combination with palmitic acid and hydrolyzed protein further reduces calcium excretion. And the inventors also surprisingly found that feeding infants with a formula containing partially hydrolyzed protein, ionic calcium and palmitic acid containing triacylglycerols results in a lower amount of calcium excretion than infants fed with a large amount of sn-2 palmitate and intact or hydrolyzed protein, but more similar to the amount of calcium excretion of infants fed with human milk.

[0059] Without being bound by any theory, the inventors of the present application believe that peptides obtained by proteolysis have a weaker protection against proteolysis of digestive enzymes compared to intact proteins. Thus, peptides from protein hydrolysates can not be able to protect the digestive enzyme lipase from proteolysis during digestion, whereas intact proteins will protect the lipase. Therefore, hydrolyzed protein peptides in combination with a palmic acid containing oil mixture will result in less release of sn-1 (3) palmitic acid from the lipase, preventing soap formation and improving calcium absorption.

[0060] This effect of hydrolyzed proteins on digestive enzymes is further improved by the addition of ionic calcium. Without being bound by any theory, the inventors believe that ionic calcium binds to peptides formed by proteolysis. These calcium bound peptides are particularly bad at protecting the lipase compared to unbound peptides formed by hydrolyzed proteins, and thus further impair lipase activity. Therefore, the less the lipase is protected, the less palmitic acid is released from the sn-1 and sn-3 positions of triglycerides, and the less calcium soap is formed. Palmitic acid will remain bound to triglycerides and be absorbed. Thus, more calcium is excreted through the feces.

[0061] In the context of the present application, the term "protein" refers to one or more proteins.

[0062] The protein used in the present application can be any protein suitable for administration to an infant. The protein source may, for example, be one or more selected from whey protein, casein, soy protein, pea protein, rice protein or protein from legumes. Preferably, however, the protein source is based on cow milk protein, such as whey, casein or a mixture thereof.

[0063] In one embodiment of the present application, the protein is a milk protein, and in a preferred embodiment, the protein is a combination of casein and whey protein.

[0064] Casein is a common milk protein in mammalian milk. Casein constitutes about 80% of the protein in cow milk and about 40% of the protein in human milk.

[0065] Whey protein is a mixture of globular proteins isolated from whey, which is a liquid material made as a by-product of cheese making processes. Whey protein constitutes about 20% of the protein in cow milk, while about 60% of the protein in human milk is whey protein.

[0066] Whey protein is typically a mixture of several proteins, such as beta-lactoglobulin, alpha-lactalbumin, lactoferrin and bovine serum albumin and immunoglobulins.

[0067] In another preferred embodiment of the present application, the protein is whey protein.

[0068] The whey protein can be in the form of, for example, whey protein isolate (WPI) or whey protein concentrate (WPC).

[0069] In one aspect of the application, the protein is a partially hydrolysed protein.

[0070] In one embodiment of the application, the partially hydrolysed protein is a partially hydrolysed whey protein.

[0071] The term "hydrolysed protein" refers to a protein which has undergone hydrolysis to break down the protein into a mixture of peptides and free amino acids. Hydrolysis of proteins is well known and can be performed by a number of different methods, for example by enzymatic hydrolysis, i.e. using enzymes such as trypsin to stimulate the naturally occurring hydrolysis process. Hydrolysis can also be performed by prolonged boiling in strong acids or alkalis. In the context of the present application, the partially hydrolysed protein can be produced by any suitable method known in the art. For example, a whey protein hydrolysate can be prepared by enzymatic hydrolysis of a whey fraction in two steps as described in EP 0322589 A1. To hydrolyse the protein sufficiently, the whey protein can be triple-hydrolysed using the enzymes Alcalase 2.4L (EC 940459) at a temperature of about 55°C, followed by Neutrase 0.5L, and then trypsin.

[0072] An example of a whey protein hydrolysate which can be used in the present application is a whey protein hydrolysate comprising about 79% protein and having a degree of hydrolysis of about 13%.

[0073] In the context of the present application, "partially hydrolysed" refers to a protein which has undergone hydrolysis in which only a part of the peptide bonds in the protein have been hydrolysed. The partial hydrolysis of a protein is measured in terms of the degree of hydrolysis.

[0074] The term "degree of hydrolysis" of a protein refers to the number of peptide bonds in the intact protein which are cleaved during hydrolysis divided by the number of peptide bonds in the intact protein, expressed as a percentage.

[0075] In the context of the present application, the term "intact" refers to a protein whose molecular structure has not been altered according to the conventional meaning of intact protein. By the term "intact" is meant that the major portion of the protein is intact, i.e. the molecular structure has not been altered, for example at least 95% of the protein has not been altered, such as at least 98% of the protein has not been altered.

[0076] In one embodiment of the application, the partially hydrolysed protein has a degree of hydrolysis of 8% to 24%, preferably 11% to 18%, such as 13% to 16%.

[0077] A partially hydrolysed protein comprises a protein in which substantially all the protein has been hydrolysed to some extent. However, a partially hydrolysed protein can comprise some intact protein, in which the peptide bonds in some of the proteins have been broken by hydrolysis. In the context of the present application, a partially hydrolysed protein hydrolysate comprises at most 10% intact protein, such as at most 5% intact protein, preferably at most 3% intact protein, even more preferably at most 1% intact protein. The term "substantially all" means that a major part has been hydrolysed, such as at least 95% of the protein has been hydrolysed, preferably at least 98% of the protein has been hydrolysed.

[0078] In one embodiment of the present application, the composition, such as an infant formula, can comprise a partially hydrolysed protein hydrolysate and another protein source comprising intact protein. For example, the protein source can comprise intact protein and partially hydrolysed protein, such as a whey protein isolate. Furthermore, the composition or infant formula according to the present application can comprise a partially hydrolysed protein hydrolysate and another protein source, which other protein source comprises intact protein. For example, a partially hydrolysed whey protein isolate and skim milk protein.

[0079] The amount of hydrolysed protein should be at least 50%, such as at least 60%, preferably at least 70%, such as at least 80%, even more preferably at least 90%, based on total protein.

[0080] Skim milk (may also be referred to as skimmed milk) is a product made from whole milk, in which substantially all the milk fat has been removed from the product. In skim milk, the amount of fat is zero to 0.3%. Thus, skim milk will comprise whey protein and casein.

[0081] Another example can be a combination of a partially hydrolysed whey protein isolate and whole milk protein.

[0082] In one embodiment of the present application, the content of partially hydrolysed protein is at least 5 g / L, such as at least 7 g / L, preferably at least 9 g / L. For example, the content of protein in the composition is 5 g to 35 g / L, such as 8 g to 30 g / L, preferably 9 to 17 g / L or 15 to 30 g / L.

[0083] In yet another embodiment of the present application, the ratio between partially hydrolysed protein and sn-2 palmitate is 1.5:1 to 35:1 by weight, such as 2.0:1 to 30:1, preferably 2.5:1 to 25:1, even more preferably 2.5:1 to 15:1, such as 2.5:1 to 10:1 by weight.

[0084] In yet another embodiment of the application, the ratio between the partially hydrolyzed protein and the sn-1 (3) palmitate is between 2:1 and 20:1 by weight, such as between 2.5:1 and 15:1, preferably between 3:1 and 10:1 by weight.

[0085] Calcium: In one aspect of the application, the composition comprises ionic calcium.

[0086] The ionic calcium can be any calcium source suitable for administration to an infant. For example, the ionic calcium can be one or more selected from the group consisting of calcium citrate, calcium hydroxide, calcium oxide, calcium chloride, calcium carbonate, calcium gluconate, calcium phosphate, calcium pyrophosphate, calcium triphosphate, calcium glycerophosphate, calcium lactate, and calcium sulphate.

[0087] In a preferred embodiment, the ionic calcium is one or more selected from the group consisting of calcium hydroxide, calcium chloride, and calcium citrate.

[0088] However, the ionic calcium can also be one or more selected from the group consisting of calcium phosphate, calcium gluconate, and calcium carbonate.

[0089] In the context of the present application, ionic calcium refers to calcium that is not attached to a protein. The ionic calcium can also be referred to as free calcium. The ionic calcium can be measured using ionometry.

[0090] Calcium phosphate is not ionic per se, but the chemical reactions that take place under digestion release some free calcium. For example, calcium pyrophosphate obeys the following solubility equilibrium:

[0091] Thus, in the context of the present application, calcium phosphate is considered a source of ionic calcium.

[0092] In one embodiment of the application, the composition has an ionic calcium content of at least 1.7 mmol / L.

[0093] The inventors of the present application have surprisingly found that ionic calcium in combination with a hydrolyzed protein hydrolysate and a palm acid containing oil mixture provides an improved effect on calcium excretion, which can improve calcium absorption. Without being bound by any theory, the inventors of the present application believe that ionic calcium provides a significant calcium-peptide interaction, where the peptide is from the hydrolyzed protein, which indirectly affects different digestive enzymes. The calcium-peptide creates a weaker protection against lipase compared to intact protein and peptides not bound to calcium. Lipase is responsible for releasing sn-1 (3) palmitate from triacylglycerol under digestion, and less sn-1 (3) palmitate will be released when a blend of hydrolyzed protein and calcium is present. This reduces the formation of palmitic acid soap, and thus more calcium can be absorbed.

[0094] Furthermore, ionic calcium and magnesium are able to form bridges between negatively charged protein molecules and substantially increase the formation of whey protein's re- precipitate. These calcium and magnesium bridges are more readily formed during heat denaturation, which favours the formation of a more flexible open structure of protein chains.

[0095] In yet another embodiment of the application, the composition has an ionic calcium content of at least 2.0 mmol / L, such as at least 2.2 mmol / L, preferably at least 2.5 mmol / L.

[0096] In yet another embodiment of the application, the composition has an ionic calcium content of 1.7 to 5.0 mmol / L, such as 2.0 to 4.5 mmol / L, preferably 2.5 to 4.2 mmol / L, such as 3.0 to 4.0 mmol / L.

[0097] Infant formula: In one aspect, the composition according to the application is an infant formula.

[0098] However, in another aspect, the composition according to the application is a fortifier or supplement for human breast milk or an infant formula, or the composition is a composition to be used for the preparation of an infant formula.

[0099] In the context of the present application, the term "infant formula" refers to an infant formula comprising the nutrients that an infant typically requires to obtain proper growth, wherein the infant formula comprises protein, carbohydrate, lipids, vitamins, minerals and trace elements.

[0100] The infant formula according to the application can be a starter formula suitable for infants from birth to 4 to 6 months of age, which provides all the nutrients suitable for this age group (both for term and preterm infants). Furthermore, the infant formula can be a follow-on formula suitable for infants between four and six months of age and twelve months of age, which is typically fed to the infant in combination with increasing amounts of food such as infant cereals and fruit and vegetable purees, and other foods during weaning.

[0101] The infant formula according to the application comprises an oil mixture, wherein the oil mixture comprises palmitic acid, and wherein the proportion of sn-2 palmitic acid is at least 35% based on total palmitic acid. Thus, the amount of sn-1 (3) palmitic acid is less than 35% by weight of total palmitic acid.

[0102] In one embodiment according to the application, the oil mixture comprises sn-2 palmitate in an amount of 2-15% of the total fatty acids present in the oil mixture, and sn-1 (3) palmitate in an amount of 5-14% of the total fatty acids in the oil mixture.

[0103] The oil mixture can comprise other fatty acids than palmitic acid, most of which are bound to triacylglycerols, but some of which can be present as free fatty acids. Examples of other fatty acids are stearic acid and myristic acid (like palmitic acid, saturated acids), monounsaturated fatty acids (e.g. oleic acid), and polyunsaturated fatty acids (e.g. linoleic acid, alpha-linolenic acid, arachidonic acid and docosahexaenoic acid).

[0104] In a preferred embodiment, the oil mixture comprises stearic acid.

[0105] Typically, the oil mixture content of the infant formula is 20 to 45 g / L of infant formula.

[0106] All features and embodiments described above in connection with the oil mixture, the palmitic acid, the hydrolyzed protein and the ionic calcium in relation to the composition according to the application also apply to the infant formula.

[0107] Thus, in one embodiment, the infant formula comprises an oil mixture, wherein the palmitic acid content of the oil mixture is 15 to 25 wt%, such as a content of 18 to 22 wt%.

[0108] The protein content in infant formula (term and preterm) is typically 1.6 to 3.6 g / 100 kcal, but can be lower. The protein content in starter formula is in the lower range, while the protein content in follow-on formula is at the upper end of the range.

[0109] In yet another embodiment, the protein content of the infant formula is 5.0 to 35.0 g / L.

[0110] As mentioned before, not all of the protein present in the infant formula can be hydrolyzed protein, but part of the protein in the infant formula can be another protein source, which is for example intact. However, to obtain the desired effect, a specific amount of hydrolyzed protein must be present in the infant formula. Thus, the amount of partially hydrolyzed protein in the infant formula is at least 50% of the total amount of protein, such as at least 60% of the total amount of protein, preferably at least 70% of the total amount of protein, and even more preferably at least 80% of the total protein. In one embodiment, the protein present in the infant formula is substantially all partially hydrolyzed protein.

[0111] By the term "substantially all" is meant the major part, i.e. substantially all of the protein is partially hydrolyzed, for example at least 95% is partially hydrolyzed, such as at least 98%.

[0112] The infant formula according to the present application can also comprise a carbohydrate source. The composition can comprise one or more carbohydrates. The preferred carbohydrate source is lactose, but other carbohydrates such as sucrose, maltodextrin and starch can also be added. Preferably, between 9 and 14 g / 100 kcal of carbohydrate is present in the infant formula according to the present application. Preferably, the carbohydrate present in the infant formula is lactose.

[0113] The infant formula can also comprise all vitamins and minerals considered essential for the daily diet, which are present in the infant formula in nutritionally significant amounts. Minimum requirements have been established for certain vitamins and minerals. Examples of minerals, vitamins and other nutrients present in the nutritional composition include vitamin A, vitamin B1, vitamin B2, vitamin B6, vitamin E, vitamin K, vitamin C, vitamin D, folic acid, inositol, niacin, biotin, pantothenic acid, choline, calcium, phosphorus, iodine, iron, magnesium, copper, zinc, manganese, chloride, potassium, sodium, selenium, chromium, molybdenum, taurine and L-carnitine. Minerals are usually added in the form of salts.

[0114] Other components such as prebiotics, prebiotic fibres, emulsifiers and stabilisers can be added to the infant formula.

[0115] Preparation: The composition and infant formula according to the present application can be prepared by any known or otherwise suitable means. For example, the infant formula can be prepared by mixing together the protein source with the carbohydrate source and the lipid source in suitable proportions. If an emulsifier is used, it can be added at this stage. Vitamins and minerals can be added at this stage, but can also be added later, in order to avoid thermal degradation. Water, preferably reverse osmosis or deionised water, can then be added and mixed in, to form a liquid mixture. The temperature of mixing is preferably room temperature, but can also be higher. The liquid mixture can then be heat treated, in order to reduce the bacterial load. The mixture can then be homogenised.

[0116] If a powdered composition is desired, the homogenised mixture is dried in a suitable drying apparatus, such as a spray drier or a freeze drier, and converted into a powder.

[0117] The process for the manufacture of infant and baby formulae is based on the concept that the product must be nutritionally adequate and safe to consume from a microbiological point of view. Therefore, steps to eliminate or limit microbial growth are essential to the manufacturing process. The processing technique for each particular formula is the property of the manufacturer, but in general, for powder products it involves the preservation of an oil-in-water (o / w) emulsion by dehydration, or for ready-to-feed or concentrated liquid products it involves sterilization. Powdered infant formulae can be produced by various methods, such as dry mixing of the dehydrated ingredients to constitute a uniform formula, or hydration and wet mixing of a mixture of macro-ingredients such as fat, protein and carbohydrate ingredients, followed by evaporation and spray-drying of the resulting mixture. A combination of the two methods can be used, where a base powder is first prepared by wet mixing and spray-drying of all or some of the macro-ingredients, followed by dry mixing of the remaining ingredients, including carbohydrates, minerals and vitamins and other micronutrients, to give the final formula. Liquid formulae are provided in ready-to-feed form or as a concentrated liquid which needs to be diluted with water, usually 1 :1. The manufacturing process for these products is similar to those used for the manufacture of reconstituted milk.

[0118] If a liquid infant formula is to be produced, the homogenized mixture is filled into suitable containers, preferably under aseptic conditions. However, it is also possible to retort the liquid composition in the container, suitable apparatus for carrying out such filling and retorting are commercially available.

[0119] Use of the composition / infant formula: The present application also relates to the composition or infant formula according to the present application for use in reducing the calcium excretion of an infant or baby. The composition or infant formula is administered to the infant by feeding the infant.

[0120] The infant can be any infant, i.e. a term infant and a preterm infant. The composition or infant formula according to the present application can advantageously be administered to an infant or baby. In a particular embodiment, it is for an infant of less than 12 months, i.e. less than 6 months or less than 3 months. In one embodiment, the composition or infant formula is a preterm infant formula. In another embodiment, the composition or infant formula is designed to be consumed by an infant from birth to 12 months of age.

[0121] The product of the present application can be in a fluid (liquid) form. These products can be sold in ready-to-feed form (without further dilution required).

[0122] The product of the present application can be in the form of a dehydrated powder which is prepared for post-consumption reconstitution with water or milk.

[0123] The product of the application can also be in the form of an extruded snack product, in particular for young children.

[0124] Furthermore, the present application relates to a composition or infant formula according to the present application for use in improving calcium homeostasis, increasing calcium absorption, increasing calcium retention, increasing calcium utilization and / or reducing insoluble palmitic acid soap formation in an infant or young child.

[0125] Without being bound by theory, increased calcium absorption is believed to have beneficial physiological effects as well as playing a role in bone mineralization. The inventors of the present application surprisingly found that if ionized calcium is combined with a mixture of hydrolyzed protein and palmitic acid containing oil for use in an infant formula, a synergistic effect is obtained and the efficiency of calcium absorption is higher compared to using a composition comprising a mixture of palmitic acid containing oil combined with intact protein or with hydrolyzed protein. Without being bound by any theory, it is believed that the hydrolyzed protein influences the action of pancreatic lipase to release palmitic acid from the sn-1 and sn-3 (a) positions of triacylglycerols. Thus, when hydrolyzed protein is present, less sn-1 (3) palmitic acid is released from triacylglycerols and thus less free palmitic acid is available to form soap with calcium. The reduced palmitic acid soap can result in reduced constipation and improved gastrointestinal tolerance compared to standard infant formula. Thus, more calcium is absorbed when less calcium is excreted.

[0126] Furthermore, the combination of ionized calcium with hydrolyzed protein further reduces the action of lipase because calcium binds to peptides from the hydrolyzed protein. Thus, the hydrolyzed protein and ionized calcium provide a synergistic effect such that less palmitic acid is released from the sn-1 and sn-3 positions of triacylglycerols.

[0127] Thus, if hydrolyzed protein and ionized calcium are present, less sn-2 palmitic acid is released and thus less free palmitic acid is released that can bind to free calcium. Thus, less palmitic acid soap is formed. The reduced palmitic acid soap can result in reduced constipation and improved gastrointestinal tolerance compared to standard infant formula. Thus, more calcium is absorbed when less calcium is excreted.

[0128] Similar calcium excretion effects can be obtained with a formula comprising a mixture of palmitic acid containing oil, hydrolyzed protein and ionized calcium that are similar to the calcium excretion obtained when human milk is used.

[0129] The present application also relates to a composition or infant formula according to the present application, for use in administering to an infant or young child for softening stools, preventing stool hardening and digestive discomforts associated with stool hardening and / or reducing the risk of stool hardening and digestive discomforts associated with stool hardening, preventing constipation and / or reducing the risk of constipation, reducing the frequency and duration of crying, and relieving digestive discomforts and colic. The relief of digestive discomforts can improve sleep duration, improve sleep quality and quantity, improve the quality of life of the infant and the parents, and reduce maternal anxiety.

[0130] Increased calcium absorption and retention can result in increased bone mineralization. The increased calcium absorption is due to the reduced formation of calcium soaps, which are not well absorbed but are instead excreted. These palmitic acid soaps (calcium-fatty acid complexes) can make stools harden when excreted in the stool. Therefore, it is also an object of the present application to soften stools.

[0131] Furthermore, one aspect of the present application relates to a composition or infant formula according to the present application, for use in administering to an infant or young child for increasing bone mineralization, increasing bone strength and increasing bone mineral density.

[0132] Especially for preterm infants or infants with low or very low birth weight, which have a high incidence of metabolic bone disease of 30-50%, it is therefore desirable to increase bone mineralization in such infants. Metabolic bone disease increases the risk of bone fractures and abnormal growth. It is believed that insufficient calcium absorption is a major factor in metabolic bone disease.

[0133] It should be noted that embodiments and features described in the context of one of the aspects of the present application also apply to the other aspects of the present application.

[0134] All patents and non-patent literature references cited in the present application are hereby incorporated by reference in their entirety.

[0135] The present application will now be described in further detail in the following non-limiting examples.

[0136] Example

[0137] The following examples illustrate specific embodiments of the composition and infant formula according to the present application and the use of the composition and infant formula. These examples are given only for illustrative purposes and should not be construed as limiting the present application, as many variations of the present application can be made without departing from the spirit thereof.

[0138] Example 1

[0139] Example 1 describes a comparison of different studies, which were performed to study infants fed with different infant formulas and compared to a control infant formula.

[0140] In Group I, infants were fed an infant formula comprising intact protein and a fat blend comprising triacylglycerols with 35.9% palmitic acid at the sn-2 position of the triacylglycerols. The infants were fed the infant formula for four weeks and then the fecal palmitic acid soap (calcium palmitate complex), total fatty acid soap, and calcium were measured and compared to the amounts in a control infant formula.

[0141] In Group II, infants were fed an infant formula comprising intact protein and a fat blend comprising triacylglycerols with 35.9% palmitic acid at the sn-2 position of the triacylglycerols, as in Group I. The infants were fed the infant formula for eight weeks and then the fecal palmitic acid soap (calcium palmitate complex), total fatty acid soap, and calcium were measured and compared to the amounts in a control infant formula.

[0142] In Group III, infants were fed an infant formula comprising partially hydrolyzed protein and a fat blend comprising triacylglycerols with 35.9% palmitic acid at the sn-2 position of the triacylglycerols. The infants were fed the infant formula for eight weeks and then the fecal palmitic acid soap (calcium palmitate complex), total fatty acid soap, and calcium were measured and compared to the amounts in a control infant formula.

[0143] The control infant formula comprised a fat blend with an amount of beta-palmitic acid of about 11.7%. In addition, the control formula comprised standard intact bovine milk protein as the protein source.

[0144] The calcium content of the feces was also measured for a group of infants fed human milk.

[0145] The primary objective of these studies was to measure the amount of calcium and calcium fatty acid soap in the feces of infants fed different infant formulas and compared to a control infant formula.

[0146] The three test formulas (Groups I, II, and III) and the control formula were prepared as ready-to-feed liquids. The three test formulas and the control formula are described in Table 1A below.

[0147] Table 1A:

[0148] The ionized calcium content of Groups III and the control group is shown in Table IB below:

[0149] The calcium excreted in the feces was measured in the three groups and the control formula.

[0150] Table 2 below shows the fecal calcium content measured in the stools of infants in Groups I, II, and III. In addition, Table 2 shows the fecal calcium content of infants fed a control formula and infants fed human breast milk. Table 2 also shows the calcium content of the different infant formulas.

[0151] Table 2:

[0152] NS = not significant; ND = not determined; NA = not applicable

[0153] As can be seen from Table 2, the calcium content of the test formulas and the control formula were essentially similar, i.e., there was no significant difference.

[0154] In addition, Table 2 shows that the fecal calcium content of infants fed the test formula in Group III was more similar to that of infants fed human breast milk than infants fed the test formula in Groups I and II. Thus, infants fed an infant formula containing a moderate amount of beta palmitic acid and partially hydrolyzed protein excreted a calcium content in their stool that was more similar to that of infants fed human breast milk than infants fed an infant formula with a high amount of beta palmitic acid and intact protein.

[0155] In addition to the calcium content excreted in the stool, the three groups were also measured for fatty acid soaps. The calcium content and fatty acid soap content of the stool were measured and compared to the content in the control formula. The data can be found in Table 3.

[0156] Table 3: : means decreased compared to control.

[0157] : means increased compared to control.

[0158] The infants in the test groups were fed the test infant formulas as the sole nutrition.

[0159] In Table 3, the infant formula containing a combination of beta palmitic acid (35.9%) and hydrolyzed protein had an improved effect on reducing the amount of palmitate calcium complex (soap) compared to an infant formula containing 35.9% palmitic acid and intact protein. Thus, it was shown that hydrolyzed protein has an effect on calcium excretion in the stool when administered with a moderate amount of beta palmitic acid. The calcium excretion of the infants in Group III was reduced by 20% compared to infants fed the control infant formula, while there was no significant difference in the calcium excretion of the infants in Groups I and II. In addition, the fecal calcium content of the infants fed in Group III was closer to the fecal calcium content in infants fed human breast milk.

Claims

1. A composition for an infant or young child formula comprising a partially hydrolysed protein, ionic calcium and an oil mixture comprising palmitic acid esterified to triacylglycerols, wherein the palmitic acid comprises palmitic acid esterified at the sn-2 position of triacylglycerols in an amount of at least 20% by weight of total palmitic acid.

2. The composition according to claim 1, wherein the ionic calcium is one or more selected from the group consisting of calcium citrate, calcium hydroxide, calcium oxide, calcium chloride, calcium carbonate, calcium gluconate, calcium phosphate, calcium pyrophosphate, calcium triphosphate, calcium glycerophosphate, calcium lactate and calcium sulphate.

3. The composition according to any one of claims 1 or 2, wherein the ionic calcium content of the composition is at least 1.7 mmol / L.

4. The composition according to any one of claims 1 to 3, wherein the partially hydrolysed protein is a partially hydrolysed whey protein.

5. The composition according to any one of claims 1 to 4, wherein the partially hydrolysed protein has a degree of hydrolysis of 8% to 24%.

6. The composition according to any one of claims 1 to 6, wherein the oil mixture comprises at least 8% by weight of palmitic acid of the total amount of fatty acids.

7. The composition according to any one of claims 1 to 6, wherein the ratio between the partially hydrolysed protein and the sn-2 palmitic acid is 1.5:1 to 35:1 by weight.

8. An infant formula comprising the composition according to any one of claims 1 to 7.

9. The infant formula according to claim 8, wherein the sn-2 palmitic acid content of the oil mixture is 15% to 25% by weight.

10. The infant formula according to claim 8, wherein the amount of partially hydrolysed protein is at least 50% of the total amount of protein.

11. The composition according to any one of claims 1 to 7 or the infant formula according to any one of claims 8 to 10 for use in administering to an infant or young child to reduce calcium excretion in the infant or young child.

12. The composition according to any one of claims 1 to 7 or the infant formula according to any one of claims 8 to 10 for use in administering to an infant or young child to improve calcium homeostasis, increase calcium absorption, increase calcium retention, increase calcium utilisation and / or reduce palmitic acid soap formation.

13. The composition according to any one of claims 1 to 7 or the infant formula according to any one of claims 8 to 10 for use in administering to an infant or young child to soften stools, prevent stool hardening and / or reduce the risk of stool hardening, prevent constipation and / or reduce the risk of constipation, improve feeding tolerance, reduce the frequency and duration of crying episodes, and relieve digestive discomfort and colic.

14. The composition according to any one of claims 1 to 7 or the infant formula according to any one of claims 10 to 14 for use in administering to an infant or young child to improve sleep duration, improve sleep quality and quantity, improve infant and parent quality of life, and reduce maternal anxiety.

15. The composition according to any one of claims 1 to 7 or the infant formula according to any one of claims 8 to 10 for use in administering to an infant or young child to increase bone mineralization, increase bone strength and / or increase bone mineral density.

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