Fat composition for preventing regurgitation in infants

Abstract

A synthetic nutritional composition for use in the treatment and / or prevention of reflux in infants, the synthetic nutritional composition comprising a carbohydrate fraction, a protein fraction and a lipid fraction wherein the amount of butyrate in the lipid fraction is at least 0.2 wt% as determined for the total amount of fatty acids in the lipid fraction; and wherein the amount of butyrate (i.e. C4: 0) attached to sn-1, 3 is greater than 70% of the total amount of butyrate.

Description

[0001] introduction

[0002] The present invention relates generally to improved nutritional products. More particularly, in one aspect, the present invention relates to synthetic nutritional compositions and methods and systems relating thereto.

[0003] To some extent, the purpose of these products is to provide necessary nutrients to consumers. In addition to providing nutrition to consumers, it is important that these products are safe to consume.

[0004] The present invention relates to a synthetic nutritional composition comprising a carbohydrate fraction, a protein fraction and a lipid fraction. More specifically, wherein the lipid fraction comprises butyrate, the amount of butyrate in the lipid fraction is at least 0.2 wt% as measured by the total amount of fatty acids in the lipid fraction; and wherein the amount of butyrate linked to sn-1,3 (i.e. C4:0) is greater than 70% of the total amount of butyrate. The present invention further relates to a synthetic composition of the present invention for use in the treatment and prevention of infant reflux. The present invention also relates to the use of a synthetic composition according to the present invention for the treatment and / or prevention of infant reflux. On the other hand, the present invention relates to a method for treating infant reflux, the method comprising the step of administering a synthetic composition of the present invention. Background Art

[0005] After birth, mothers provide the best nutrition for their infants through breastfeeding. Human milk contains a variety of valuable macro- and micronutrients, bioactive components and microbiota to nourish the newborn, while also supporting the colonization and development of the intestinal microbiota (GM). Human milk is designed to deliver nutrients to the site of action and is easily digestible due to its balanced composition and matrix. For infants, human milk is therefore the nutrition of choice (EU Directive 2006 / 141). However, if breastfeeding is not an option, there are alternatives based on cow's milk on the market, which are often supplemented with ingredients that mimic many of the functions of breast milk components, such as human milk oligosaccharides (HMOs).

[0006] A wide variety of infant formulas are available, with ingredients that differ in their origin and processing. In addition to being important sources of energy, carbohydrates, fats and proteins are considered important for regulating the intestinal comfort of infants. Most infants fed with infant formula suffer from gastrointestinal (GI) discomfort, although to varying degrees. Although these GI problems are generally considered mild and harmless to infants, when they occur, they may cause distress to affected infants and their caregivers. Distress may manifest as more and / or longer crying, irritability and sleep problems in infants, which in turn may increase the stress of their caregivers. Therefore, prevention or management of GI symptoms by nutritional methods is considered relevant and desirable. Intestinal (dis)comfort is affected by a complex combination of several formula parameters: in particular, ingredient composition and digestibility of (macro)nutrients.

[0007] The major functional gastrointestinal disorder in infants is reflux (i.e., gastroesophageal reflux: GER). The prevalence ranges from 8% to 87%, but the overall global prevalence is estimated to be 25% to 30%, peaking at 67% to 87% at 2 to 4 months of age. Reflux is the upward flow of gastric contents through the esophagus to the mouth. It may be accompanied by vomiting or not. When GER leads to troublesome complications, it is classified as GER disease (GERD). The underlying pathophysiological mechanisms include anatomical (e.g., underdeveloped esophageal sphincter and short esophagus), postural (feeding while the child is lying down), and behavioral (overfeeding) mechanisms. Because GER is transient and benign, it does not need to be treated pharmacologically (in most cases), and modifications in feeding style (smaller feedings, more upright posture) and the use of special infant formulas designed to reduce GER symptoms are recommended. There are two main approaches to managing GER:

[0008] a) Thickening the formula with thickeners such as starch, carob bean gum (CBG) or locust bean gum (LBG) will make it more difficult for the liquid in the stomach to enter the esophagus. Studies have found that appropriately thickened formula can reduce the incidence of infant vomiting. Locust bean gum is a good "natural thickener". Adding less than 1% of locust bean gum to milk powder can make the milk sink more easily to the bottom of the baby's stomach and less likely to flow back into the esophagus.

[0009] b) Increase the rate of gastric emptying by using partially hydrolyzed protein to reduce the amount of fluid available for reflux.

[0010] Locust bean gum (Robinia / Carob bean gum / CBG), also known as locust bean gum and carob bean gum, is derived from the endosperm portion of the seeds of the locust tree. It is a natural food thickener whose main component is galactomannan. Locust bean gum is a low-concentration, high-viscosity water-soluble colloid.

[0011] Therefore, there is a consensus in the prior art that GER and GERD can be treated by using specially designed formulas. In addition to existing products and solutions, there is a need for alternative infant formulas that reduce GER and / or GERD and / or help infants sleep better.

[0012] The purpose is to develop an infant formula that meets one or more of these needs. Specifically, there is a need for an alternative infant formula that treats or reduces GER and / or GERD and / or improves children's sleep without further negative effects. This composition is not only beneficial to infants because it causes less discomfort, but also beneficial to parents because the less crying of infants causes less stress to parents. Reflux is a known reason for infants to feel uncomfortable after feeding. Therefore, an object of the present invention is to develop an infant formula that prevents reflux or at least reduces the severity of reflux in infants fed with this formula.

[0013] The inventors unexpectedly found that the lipid fraction (also called fat, i.e. a glycerol unit having up to three fatty acids attached thereto by ester bonds) has a high level of butyrate at the sn1,3 position of the glycerol, and preferably a high level of long-chain saturated fatty acids at the sn-2 position of the glycerol, thereby improving fat digestion into fatty acids and increasing total lipid absorption.

[0014] The presence of distal small intestinal fat is an effective inhibitor of gastric emptying, which results in proximal gastric relaxation and distal gastric contraction attenuation. Therefore, it is believed that the digestion and absorption of fat eliminates the inhibitory stimulus, resulting in restoration of gastric motility. Therefore, the gastric emptying rate depends in particular on the digestion of fat into fatty acids. It was unexpectedly found that milk fat (MF) has such a high level of saturated fatty acids at the sn-2 position of glycerol and a high level of short chain fatty acids (SCFA) at the sn1-3 position of glycerol.

[0015] Therefore, using MF in infant formula can help gastric emptying and reduce the amount of digesta available for regurgitation.Therefore, MF can be used to treat or prevent the symptoms of GER / GERD. Summary of the invention

[0016] The invention relates to the use and method as defined in the claims.

[0017] Thus, in a first aspect, the present invention relates to a synthetic nutritional composition comprising a carbohydrate fraction, a protein fraction and a lipid fraction, wherein the amount of butyrate in the lipid fraction is at least 0.2 wt% as determined with respect to the total amount of fatty acids in the lipid fraction; and wherein the amount of sn-1,3 linked butyrate (i.e. C4:0) is greater than 70%, preferably greater than 80%, more preferably greater than 90% of the total amount of butyrate.

[0018] In another aspect, the present invention relates to a synthetic composition of the present invention for use in the treatment and / or prevention of infantile reflux; preferably the treatment of infantile reflux. In still another aspect, the present invention relates to the use of a synthetic composition according to the present invention for the treatment and / or prevention of infantile reflux; preferably the treatment of infantile reflux. In yet another aspect, the present invention relates to a method of treating infantile reflux, the method comprising the step of administering a synthetic composition of the present invention.

[0019] definition

[0020] A prerequisite for infant formula is that the final product must be microbiologically safe, and for this reason, traditional processing requires that the final product undergoes extensive heat treatment, such as pasteurization. Therefore, products in powder form are usually heat treated before spray drying. However, products in liquid form undergo more stringent treatment, such as by short exposure to high temperatures (UHT-aseptic process).

[0021] As used herein, the term "reconstituted beverage" refers to a drinkable product prepared by dissolving a powder in a liquid (such as dissolving an infant formula in water) according to the manufacturer's instructions. The drinkable product is preferably drinkable by an infant using a bottle with a nipple. Such bottles with nipples are well known and easily commercially available. The drinkable product preferably has a viscosity of less than 800 cP (at 25 ° C and a pressure of 1 atmosphere), such as between 1 cP and 500 cP, preferably between 1 cP and 400 cP, more preferably between 1 cP and 200 cP. The advantage of the product and use of the present invention is that the drinkable product (such as infant formula) does not necessarily have to become more viscous by adding a thickener such as CBG, which is more convenient for caregivers who need to prepare the product. In one other embodiment, it may be necessary to add a thickener to the composition of the present invention. In one embodiment, the synthetic composition of the present invention further comprises a thickener selected from the group consisting of locust bean gum (LBG), carob bean gum (CBG) and starch; wherein the amount of thickener is between 0.001 wt% and 5 wt%, preferably between 0.01 wt% and 2.5 wt%, more preferably between 0.1 wt% and 1.5 wt%, as determined on the dry weight of the composition.

[0022] As used herein, a formula product refers to a product that provides a reconstituted drinkable product when reconstituted with a liquid, preferably water, more preferably boiling water (which is preferably cooled to below 37°C). Once the reconstituted beverage is consumed, the temperature of the reconstituted beverage should not be too high to avoid burning the tongue or mouth of the subject. Therefore, under normal circumstances, the temperature of the liquid should be at or below 37°C.

[0023] Formula products are usually powders, but in some cases can be easily dissolved tablets or cubes. Examples of formula products include products that provide complete nutrition to the subject after reconstitution into a reconstitution beverage, such as IFT products, follow-on formula foods (FOF) and toddler formula foods (YCF-Jr). Formula products have a recommended dose (i.e., amount) of the formula product per subject per day; the number of recommended feeding times per subject per day and the recommended ratio between the desired amount of the formula product and the desired amount of liquid. These recommendations may depend on the type and brand of formula food and are provided by the manufacturer.

[0024] As used herein, the term "infant formula" refers to a nutritional composition intended for infants as defined in the Codex Alimentarius (Codex STAN 72-1981), and Infant Specialties (including foods for special medical purposes) as defined in the Codex Alimentarius (Codex STAN 72-1981). It also refers to foods intended for special nutritional use in the first few months of life for infants and which meet the nutritional needs of such people themselves (Article 2 (c) of the European Commission Directive 2006 / 141 / EC of 22 December 2006 on infant formulae and follow-on formulae)). Infant formula can encompass a section of infant formula, older infant formula or follow-on formula, and toddler formula. Generally speaking, a first-stage formula is used as a breast milk substitute for infants from birth, and follow-on formula or follow-on formula is used from the 6th month onwards. Therefore, infant formula can be designed for infants from 0 to 6 months, 6 to 12 months, or 12 months and older. Toddler formula can be designed for children aged 1-3 years.

[0025] As used herein, the term "preventing" or "preventing" with respect to a given disease or condition means preventing the development of the disease from occurring (if the disease has not yet occurred), preventing the disease or condition from occurring in a subject who may be susceptible to the condition or disease but has not yet been diagnosed with the condition or disease, and / or preventing the disease / condition from further developing (if the disease has already occurred).

[0026] As used herein, the term "treating" or "treating" with respect to a given disease or condition means preventing further disease / condition development, and / or ameliorating symptoms of the disease in the subject.

[0027] As used herein, the term "synthetic nutritional composition" is a composition that is artificially prepared and contains at least one compound produced in vitro chemically and / or biologically and / or physically, for example by a chemical reaction, an enzymatic reaction or by a fractionation process. An example of such a fractionation process is the process of separating cow's milk into different fractions, such as fat and protein fractions. For the avoidance of doubt, a synthetic composition is not produced in vivo by a human or animal.

[0028] The compositions used according to the present invention should be safe and preferably have no side effects.

[0029] Unless otherwise indicated, all amounts are per gram dry weight of the composition. Likewise, wt % or weight percentages are per gram dry weight of the composition. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] exist Figure 1 In, the results of an in vitro digestion experiment as described in Example 1 are disclosed. IF1 is an infant formula containing a fat fraction with 50 wt% milk fat and 50 wt% vegetable oil; IF2 is an infant formula containing a fat fraction with vegetable oil but no milk fat. The pH drops from neutral at the beginning to 6 to 3.5, indicating the progress of digestion in the stomach. ΔFFA is the increase in free fatty acids during gastric digestion. It can be seen from the data that at the end of gastric digestion, i.e. at pH 3.5, the amount of FFA in IF1 is significantly higher than that in IF2. DETAILED DESCRIPTION

[0031] Thus, in a first aspect, the present invention relates to a synthetic nutritional composition comprising a carbohydrate fraction, a protein fraction and a lipid fraction, wherein the amount of butyrate in the lipid fraction is at least 0.2 wt% as determined by the total amount of fatty acids in the lipid fraction; and wherein the amount of butyrate linked to sn-1,3 (i.e. C4:0) is greater than 70%, preferably greater than 80%, more preferably greater than 90% of the total amount of butyrate. In one embodiment, the lipid fraction of the composition of the present invention further comprises long chain saturated fatty acids (LC SFA) linked to glycerol, and at least 20 mol% of the LC SFA are linked to the sn-2 position of glycerol. Preferably, in one embodiment, at least 30 mol% of the LC SFA are linked to the sn-2 position of glycerol, more preferably at least 35 mol%, most preferably at least 41 mol% of the LC SFA are linked to the sn-2 position.

[0032] In another embodiment, the lipid fraction of the composition of the present invention further comprises long-chain saturated fatty acids (LC SFAs) linked to glycerol, and expressed as a percentage of all fatty acids linked to sn2, the percentage of LC SFAs on sn2 is at least 30%, preferably at least 40%; and at least 20 mol% of the LC SFAs are linked to the Sn-2 position of glycerol, preferably at least 30 mol% of the LC SFAs are linked to the sn-2 position of glycerol, more preferably at least 35 mol%, and most preferably at least 41 mol% of the LC SFAs are linked to the sn-2 position.

[0033] In another embodiment, the lipid fraction of the composition of the present invention further comprises saturated fatty acids (SFA) linked to glycerol, and at least 20 mol% of the SFA are linked to the sn-2 position of glycerol. Preferably, in one embodiment, at least 30 mol% of the SFA are linked to the sn-2 position of glycerol, more preferably at least 35 mol%, most preferably at least 41 mol% of the SFA are linked to the sn-2 position.

[0034] As used herein, the term "synthetic" means obtained by chemical and / or biological means, as opposed to "natural" (found in nature), e.g., a synthetic nutritional composition is not of human or animal origin (e.g., it is not breast milk or cow's milk). Infant formula is an example of a synthetic nutritional composition; it is intended to replicate the nutritional value of human milk, which is not a simple task.

[0035] As used herein, the term "nutritional" means that it nourishes the subject.The synthetic nutritional composition according to the invention is typically fed enterally, orally, orogastricly or nasogastricly, preferably orally, and comprises carbohydrate, fat and protein sources.

[0036] The synthetic nutritional composition according to the invention may be intended for infants and / or young children and may, for example, be formulated as an infant formula, a growing-up milk, or any other milk-based nutritional composition, a supplement (or a supplement), or as a fortifier such as a milk fortifier (e.g., a human milk fortifier). The nutritional composition may be in powder or liquid form.

[0037] Synthetic nutritional compositions tailored to infants of a particular age may be prepared by methods well known in the art for preparing synthetic nutritional compositions of the type in question, such as infant formulas, follow-on formulas, compositions for infants intended to be added to or diluted with human milk (e.g., human milk fortifiers), or foods intended for consumption by infants, either alone or in combination with HMs (e.g., complementary foods).

[0038] An exemplary method for preparing powdered infant formula customized for age is as follows. Protein sources, carbohydrate sources, and fat sources may be blended together in appropriate proportions. Emulsifiers may be included in the blend. Vitamins and minerals may be added at this point, but are typically added later to avoid thermal degradation. Any lipophilic vitamins, emulsifiers, etc. may be dissolved in the fat source before blending. Water, preferably water subjected to reverse osmosis, may then be mixed in to form a liquid mixture. The liquid mixture may then be heat treated to reduce bacterial load. For example, the liquid mixture may be rapidly heated to a temperature in the range of about 80°C to about 110°C for about 5 seconds to about 5 minutes. This may be done by injecting steam or by a heat exchanger; for example, a plate heat exchanger. The liquid mixture may then be cooled to about 60°C to about 85°C; for example, by flash cooling. The liquid mixture may then be homogenized; for example, in two stages, at about 7Mpa to about 40Mpa in the first stage, and at about 2Mpa to about 14MPa in the second stage. The homogenized mixture may then be further cooled to add any heat-sensitive components, such as vitamins and minerals. The pH and solid content of the homogenized mixture are conveniently standardized at this point. The homogenized mixture can be transferred to a suitable drying device (such as a spray dryer or freeze dryer) and converted into a powder. The powder should have a moisture content of less than about 3% by weight.

[0039] If necessary, one or more desired probiotics may be added, which may be cultured according to any suitable method and prepared for addition to infant formula by, for example, freeze drying or spray drying. Alternatively, bacterial preparations prepared in a form suitable for addition to food products such as infant formula may be purchased from professional suppliers such as Christian Hansen and Morinaga. Such bacterial preparations may be added to powdered infant formulas customized for age by dry mixing. Similarly, prebiotics and human milk oligosaccharides (HMOs) may be added to formula by dry mixing. Prebiotics and HMOs may be purchased from professional suppliers such as FrieslandCampina.

[0040] Examples of prebiotics include, but are not limited to, galacto-oligosaccharides (GOS), inulin and fructo-oligosaccharides (FOS) or combinations thereof. Examples of HMOs include, but are not limited to, 2'FL, 3FL, LNT, LNnT, 3'GL, 6'GL, 3SL, 6SL and combinations thereof. 2' fucosyllactose (2'FL) is a preferred HMO.

[0041] Human milk oligosaccharides, also known as human milk polysaccharides, are oligomers of monosaccharides that are only present in high concentrations in human breast milk. Human milk oligosaccharides promote the development of the immune system, can reduce pathogen infection and improve brain development and cognition. Human milk oligosaccharides (HMO) are the third most abundant solid component in human milk after lactose and fat. HMOs are present in concentrations of 9.9-24.9 g / L. About 200 structurally different human milk oligosaccharides are known. The composition of human milk oligosaccharides in breast milk varies from mother to mother and changes during lactation. The main oligosaccharide in 80% of all women is 2'-fucosyllactose (2'FL), which is present in human breast milk at a concentration of about 2.5 g / L. Other oligosaccharides include lactose-N-tetraose (LNT), lactose-N-neotetraose (LNnT) and lactose-N-fucopentaose (LNFP). (Bode, L (2012) Human milk oligosaccharides: every baby needs a sugar mama. Glycobiology. 22(9): 1147-1162. doi: 10.1093 / glycob / cws074). Preferably, the HMO is selected from the group consisting of 2'FL, 3FL, LNT, LNnT, LNFP, 3'GL, 3'SL and 6'SL.

[0042] In one embodiment, the protein fraction comprises goat or cow milk protein, and the amount of goat or cow milk protein in the protein fraction of the composition of the present invention is greater than 80 wt%, preferably the amount of protein is greater than 90 wt%, as measured relative to the total amount of protein in the composition. In another embodiment, the amount of cow milk protein in the protein fraction of the composition of the present invention is greater than 80 wt%, preferably the amount of cow protein is greater than 90 wt%, as measured relative to the total amount of protein in the composition. In yet another embodiment, the amount of goat protein in the protein fraction of the composition of the present invention is greater than 80 wt%, preferably the amount of goat protein is greater than 90 wt%, as measured relative to the total amount of protein in the composition.

[0043] The protein fraction may be a milk protein such as casein or whey, alternatively, a vegetable protein such as soy protein, rice protein. Preferably, it is a ruminant milk protein, more preferably from cow's milk, sheep's milk or goat's milk or a combination thereof, most preferably from cow's milk. WPC and SPC are well known milk fractions containing whey proteins. Both WPC and SPC are the result of separating skim milk into casein-rich and whey-rich fractions; by curdling (i.e. cheese making), acidification or microfiltration.

[0044] Whey protein concentrate (WPC) is a product obtained by ultrafiltration and optionally reverse osmosis of acid or cheese whey to further concentrate the product (remove water), and optionally demineralization. By ultrafiltration, most of the water, lactose and ash are removed from the product, thereby concentrating the whey protein. Reverse osmosis can be used to remove water and further concentrate WPC.

[0045] Serum protein concentrate (SPC) is also a concentrated protein product, which differs from WPC in the source of the whey fraction. In contrast to acid whey or cheese whey, the protein in SPC comes from the microfiltration of skim milk. The microfiltration produces a concentrated casein retentate fraction and a serum fraction containing most of the whey protein as a permeate fraction. Routinely, this permeate fraction is then subjected to ultrafiltration and / or reverse osmosis to remove lactose, ash and water. If desired, the product obtained can be demineralized.

[0046] As used herein, FA refers to fatty acids; SFA refers to saturated fatty acids, and LC SFA refers to long-chain saturated fatty acids. Long-chain saturated fatty acids refer to saturated fatty acids having 12 or more carbon atoms.

[0047] The lipid fraction in the synthetic composition of the present invention may comprise different oils, such as vegetable oils, fish oils, ruminant milk fat or a combination thereof. Preferably, the composition comprises ruminant milk fat, more preferably a combination of vegetable oils and ruminant milk fat. Even more preferably, this combination of lipids is supplemented with fish oil.

[0048] Fats consist of a glyceride residue linked to a carboxylic acid via an ester bond. Thus, a fat molecule contains a glyceride residue and three fatty acid acyl groups. The acyl group linked to the first carbon of the glyceride is also called a sn1-linked acyl group, just as the acyl group linked to the second carbon of the glyceride is called a sn2-linked acyl group and the acyl group linked to the third carbon of the glyceride is called a sn3-linked acyl group.

[0049] An acyl group contains a carbonyl group (a C double-bonded oxygen atom) attached to an alkyl group, R; (RC=O). In organic chemistry, an acyl group (IUPAC name: alkanoyl) is typically derived from a carboxylic acid and has the chemical formula RCO-, where R represents an alkyl group attached to the carbon atom of the C=O group by a single bond. As used herein, an alkanoyl group refers to the name of the corresponding anion, which is the conjugate base of the acid. For example, a C4 acyl group (CH3-CH2-CH2-C(O)-) refers to butyrate or C4:0, where the "4" refers to the total number of carbon atoms in the group and the "0" refers to the number of unsaturated carbon-carbon bonds. Similarly, C16:0 refers to palmitic acid (CH3(CH2) 14COOH) and palmitate refers to CH3(CH2) 14 CO.

[0050] The lipid fraction in the composition for use of the present invention may comprise a mixture of different oils, such as a mixture of vegetable oils and milk fat. Optionally, long chain polyunsaturated fatty acids (LC-PUFA) (such as selected from the group consisting of DHA, ARA and EPA in one embodiment) can be added to the lipid fraction; preferably, the composition comprises DHA, ARA and EPA. Such LC-PUFA is present in fish oil. It should be understood that fish oil can be replaced by polyunsaturated fatty acids (PUFA) from any other source providing docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA) and optionally arachidonic acid (ARA).

[0051] The lipid fraction in the synthetic composition of the present invention comprises at least 0.2 wt% butyrate, preferably at least 0.5 wt%, more preferably at least 1.0 wt%, particularly preferably at least 1.5 wt%, most preferably at least 1.8 wt%, as determined based on the total amount of fatty acids in the lipid fraction; further, the amount of butyrate (C4:0) linked to sn-1,3 is greater than 70%, preferably greater than 80%, more preferably greater than 90% of the total amount of butyrate.

[0052] In another embodiment, the lipid fraction of the synthetic composition of the present invention comprises at least 0.5 wt% butyrate, and further, the amount of butyrate linked to sn-1,3 is greater than 70% of the total amount of butyrate, preferably greater than 80%, more preferably greater than 90%. Preferably, in another embodiment, the lipid fraction of the synthetic composition of the present invention comprises at least 1.0 wt% butyrate, and further, the amount of butyrate linked to sn-1,3 is greater than 70% of the total amount of butyrate, preferably greater than 80%, more preferably greater than 90%. More preferably, in another embodiment, the lipid fraction of the synthetic composition of the present invention comprises at least 1.5 mol%, and further, the amount of butyrate linked to Sn-1,3 is greater than 70% of the total amount of butyrate, preferably greater than 80%, more preferably greater than 90%. Even more preferably, in another embodiment, the lipid fraction of the synthetic composition of the present invention comprises at least 1.8 wt%, and further, the amount of butyrate linked to Sn-1,3 is greater than 70% of the total amount of butyrate, preferably greater than 80%, more preferably greater than 90%.

[0053] In one embodiment the amount of milk fat is at least 10 wt%, preferably at least 20 wt%, more preferably at least 30 wt%, even more preferably at least 40 wt%, most preferably at least 50 wt% as measured relative to the total amount of fat in the composition of the invention.

[0054] In yet another embodiment, the lipid fraction further comprises vegetable oil, and the amount of vegetable oil is at least 10 wt%, preferably at least 20 wt%, more preferably at least 30 wt%, most preferably at least 40 wt% as measured relative to the total amount of fat in the synthetic composition of the present invention.

[0055] Preferably, in an embodiment, the amount of milk fat, as measured relative to the total amount of fat in the composition of the present invention, is at least 10wt%, and the amount of vegetable oil, as measured relative to the total amount of fat in the synthetic composition of the present invention, is at least 10wt%, preferably at least 20wt%, more preferably at least 30wt%, most preferably at least 40wt%.

[0056] Preferably, in an embodiment, the amount of milk fat, as measured relative to the total amount of fat in the composition of the present invention, is at least 30wt%, and the amount of vegetable oil, as measured relative to the total amount of fat in the synthetic composition of the present invention, is at least 10wt%, preferably at least 20wt%, more preferably at least 30wt%, most preferably at least 40wt%.

[0057] Preferably, in an embodiment, the amount of milk fat, as measured relative to the total amount of fat in the composition of the present invention, is at least 40wt%, and the amount of vegetable oil, as measured relative to the total amount of fat in the synthetic composition of the present invention, is at least 10wt%, preferably at least 20wt%, more preferably at least 30wt%, most preferably at least 40wt%.

[0058] Preferably, in yet another embodiment, the amount of milk fat, as measured relative to the total amount of fat in the composition of the present invention, is at least 50 wt%, and the amount of vegetable oil, as measured relative to the total amount of fat in the synthetic composition of the present invention, is at least 10 wt%, preferably at least 20 wt%, more preferably at least 30 wt%, most preferably at least 40 wt%.

[0059] Vegetable oils for human consumption are well known in the art and include sunflower oil, palm oil, and rapeseed oil.

[0060] Suitable milk fat for the composition of the present invention is mammalian milk fat. Preferably milk fat from ruminants, more preferably wherein the milk fat is selected from the group consisting of: cow milk fat, sheep milk fat, goat milk fat, camel milk fat and horse milk fat; even more preferably from cow milk fat or goat milk fat; most preferably cow milk fat, particularly preferably cow milk fat. Milk fat can be obtained from different milk fractions, such as whole milk, cream, butter, anhydrous milk fat, etc. The term "ruminant milk fat" as used in this regard refers to a milk fat source from the milk of a ruminant, preferably cow milk fat. In principle, the milk fat source can be any available ruminant milk fat source, such as whole milk, cream, anhydrous milk fat (AMF) or a milk fat fraction produced by dry fractionation, critical CO2 extraction or other fractionation methods known in the art. However, it is found to be particularly suitable to use whole milk and / or cream as a milk fat source.

[0061] Preferably, the ruminant milk fat is bovine milk fat, and the fat is selected from the group consisting of whole milk, cream, and anhydrous milk fat (AMF). More preferably, the cow is a dairy cow. In one embodiment, the milk fat is bovine whole milk or cream. In one embodiment, the ruminant milk fat is bovine whole milk; in another embodiment, the ruminant milk fat is cow milk oil; in still another embodiment, the ruminant milk fat is bovine AMF.

[0062] In still another embodiment, the protein in the protein fraction of the composition of the present invention is partially hydrolyzed. This improves the digestibility of the composition, thereby helping to prevent and / or treat GER (D). In one embodiment, the protein fraction contains at least 10 wt% of partially hydrolyzed protein as measured by the total amount of protein. Hydrolyzed proteins suitable for the composition of the present invention can be obtained using methods known in the art, such as by chemical hydrolysis or enzymatic hydrolysis, such as disclosed in WO 2006130204 or EP 0922392. As used herein, the hydrolyzed protein has a molar mass of 5000 Daltons or less.

[0063] Alternatively or additionally, in one embodiment, the composition of the present invention further comprises a thickener, in another embodiment, the thickener is selected from the group consisting of: locust bean gum (LBG), carob bean gum (CBG) and starch; preferably, wherein the amount of thickener is between 0.001 wt% and 5 wt%, more preferably between 0.01 wt% and 2.5 wt%, even more preferably between 0.1 wt% and 1.5 wt%, as determined on the dry weight of the composition.

[0064] In still another embodiment, the synthetic nutritional product is a complete nutritional product, preferably an infant formula product, such as a neonatal food product, an IFT product, a follow-on formula (FOF) and / or a toddler formula (YCF-Jr). Preferably, the product is an IFT product, a follow-on formula (FOF) and / or a toddler formula (YCF-Jr).

[0065] The composition of the present invention may further comprise vitamins and minerals. The level and type of added vitamins and minerals depends on the type of product and is known to those skilled in the art.

[0066] The composition of the present invention may be used for the treatment and / or prevention of infantile reflux (GER / GERD). Thus, in one aspect, the present invention relates to a synthetic composition of the present invention for use in the treatment and / or prevention of infantile reflux; preferably for the treatment of infantile reflux. In another aspect, the present invention relates to the use of a synthetic composition according to the present invention for the treatment and / or prevention of infantile reflux; preferably for the treatment of infantile reflux. In yet another aspect, the present invention relates to a method for the treatment of infantile reflux, the method comprising the step of administering a synthetic composition of the present invention.

[0067] In still another aspect, the present invention relates to the use of the composition of the present invention for increasing the digestion of lipids into free fatty acids in the stomach, as measured by the level of free fatty acids, and compared with infant formulas having similar macronutrient levels comprising a fat fraction consisting essentially of vegetable oils and fats, an increase of at least 15%. Preferably, the increase in free fatty acids is at least 30%, more preferably at least 45%, most preferably at least 60%. In one embodiment, the fat fraction in the composition of the present invention comprises at least 50wt% milk fat, and the increase in free fatty acids is at least 30%, preferably at least 45%, more preferably at least 60%. In another embodiment, the fat fraction in the composition of the present invention comprises at least 30wt% milk fat, and the increase in free fatty acids is at least 20%, preferably at least 25%, more preferably at least 30%. In yet another embodiment, the fat fraction in the composition of the present invention comprises at least 20wt% milk fat, and the increase in free fatty acids is at least 15%, preferably at least 20%, more preferably at least 30%.

[0068] In yet another aspect, the invention relates to the use of a composition according to the invention for the manufacture of a medicament for treating and / or preventing reflux in infants. In another aspect, the invention relates to the use of a composition according to the invention for the manufacture of a medicament for increasing the digestion of lipids into free fatty acids in the stomach, as measured by the level of free fatty acids, and an increase of at least 15% compared to an infant formula with similar macronutrient levels comprising a fat fraction consisting essentially of vegetable oils and fats; preferably, the increase in free fatty acids is at least 30%, more preferably at least 45%, most preferably at least 60%.

[0069] In a preferred aspect, the composition of the present invention does not contain yak milk.

[0070] It must also be noted that, as used in the specification, aspects, embodiments and appended claims, the singular forms "a", "an" and "the" include plural referents unless the context clearly dictates otherwise. For example, components mentioned in the singular are intended to include plural components.

[0071] Unless defined otherwise, all technical and scientific terms used herein generally have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.

[0072] Except in the examples or otherwise explicitly indicated, all numerical values ​​indicating the amount of material or reaction and / or use conditions in the specification should be understood as being modified by the word "about" when describing the broadest scope of the invention. It is usually preferred to implement within the stated numerical limits. In addition, unless explicitly stated to the contrary: percentages, "parts" and ratio values ​​are by weight; descriptions of groups or classes of materials suitable or preferably used for a given purpose related to the present invention mean that mixtures of any two or more components of the group or class may be equally suitable or preferred; descriptions of ingredients in chemical terms refer to the ingredients when added to any combination specified in the specification, and do not necessarily exclude chemical interactions between the ingredients of the mixture once mixed; the first definition of an acronym or other abbreviation applies to all subsequent uses of the same abbreviation herein, and the necessary modifications are applied to normal grammatical variations of the initially defined abbreviation; and, unless explicitly stated to the contrary, the measurement of a property is determined by the same technique as the same property cited previously or later.

[0073] Hereinafter, the present invention is illustrated with reference to the following non-limiting examples.

[0074] Examples

[0075] Fatty acid determination

[0076] The content of different fatty acids in the lipids of the composition of the invention can be determined by the standard methods ISO 15884 / IDF 182:2002 (milk fat - preparation of fatty acid methyl esters) and ISO15885 / IDF 184 (milk fat - determination of fatty acid composition by gas-liquid chromatography). These ISO methods allow the determination of the molar concentration of fatty acids relative to the total number of moles of this fatty acid in TAG ([FA-TAG]). The distribution of fatty acids on the glycerol backbone can be determined according to the method disclosed in JOCS / AOCS Official Method Ch 3a-19: Determination of the composition of fatty acids at the 2-position of oils and fats by enzymatic transesterification using Candida antarctica lipase (approved in 2019). In essence, this method involves the hydrolysis of triacylglycerols (TAG) using sn-1,3 specific pancreatic lipase (porcine). The desired 2-monoacylglycerols formed were separated by thin layer chromatography and then methylated for gas chromatography analysis and quantified in molar concentration relative to the total moles of fatty acids in the sn-2 position ([FA(sn-2)]).

[0077] experiment

[0078] Two different infant formulas (IF1 and IF2) were used in this experiment. The fat fraction in IF1 consisted of a blend of vegetable oil and milk fat (fat blend containing 50 wt% milk fat). The fat fraction in IF2 consisted of vegetable oil (IF2). The macronutrient levels of IF1 and IF2 are shown in Table 1.

[0079] Table 1 Macronutrient levels of IF1 and IF2.

[0080]

[0081] *50% of which is milk fat

[0082] Table 2 Fatty acid composition of IF1 and IF2*.

[0083]

[0084] IF1 and IF2 were subjected to an in vitro digestion model simulating infant conditions according to INFOGEST conditions (as described in Brodkorb et al. Nat Protoc. 2019 Apr;14(4):991-1014). Over time, the pH of the samples decreased, indicating a longer duration in the stomach. During simulated gastric acidification, samples were taken (i.e., sampled) at different fixed pHs (from neutral to acidic pH) and analyzed for lipid digestion. Compared to the formula containing vegetable oil alone (IF2), the formula containing milk fat (IF1) had higher gastric lipid digestion during simulated infant digestion, as shown by increased free fatty acid (FFA) levels, which is a result of triglyceride hydrolysis during gastric digestion. This was Figure 1 As shown in Figure 1 As shown, ΔFFA refers to the amount of free fatty acids (FFA) released during the gastric digestion experiment.

[0085] As can be seen from the data, at the end of gastric digestion, i.e., pH 3.5, the amount of FFA in IF1 was significantly higher than that in IF2 (230 μmol and 137.5 μmol, respectively). Therefore, replacing 50 wt% of the vegetable oil resulted in an increase of about 67% in fat digestion in the stomach. It is believed that this increased lipid digestion in the stomach improves digestion of products (e.g., infant formula) and / or reduces the level of GER / GERD.

[0086] explain

[0087] Compared to vegetable oils, milk fat has a more complex triglyceride structure, especially with more saturated fatty acids at the sn-2 position and a greater percentage of short-chain fatty acids at the sn1-3 position than vegetable oils. The latter in particular may explain the observed higher gastric lipid digestion of formula foods containing milk fat. Because of the known differences between human milk and IF regarding (gastric) lipid digestion, this is generally beneficial for IF. For example, studies in infants have demonstrated that gastric lipid digestion of human milk is higher than that of formula foods (Armand et al. Pediatr Res. [Pediatric Research] 1996 Sep; 40(3): 429-37).

[0088] Gastric lipid digestion of human milk is higher than that of infant formula containing mainly vegetable oils and fats (Armand et al. Pediatr Res. 1996 Sep; 40(3): 429-37).

[0089] Extrapolation of these results

[0090] The presence of distal small intestinal fat is a potent inhibitor of gastric emptying, specifically leading to proximal gastric relaxation and reduced distal gastric contraction, which inhibits gastric emptying. Higher gastric digestion of lipid sources may allow for more rapid fat absorption in the proximal small intestine, thereby potentially reducing the inhibitory stimulus of distal small intestinal lipids on overall gastric emptying, which could benefit infants with GER(D).

[0091] Formula containing milk fat (50% of the fat fraction was milk fat, IF1) had higher gastric lipid digestion during simulated infant digestion compared to formula containing vegetable oil (IF2), as shown by the increase in free fatty acid levels during gastric digestion (from neutral pH to acidic pH).

[0092] Numbered Examples

[0093] 1. A synthetic nutritional composition comprising a carbohydrate fraction, a protein fraction and a lipid fraction, wherein the amount of butyrate in the lipid fraction is at least 0.2 wt % as determined by the total amount of fatty acids in the lipid fraction; and wherein the amount of sn-1,3 linked butyrate (i.e. C4:0) is greater than 70%, preferably greater than 80%, more preferably greater than 90% of the total amount of butyrate.

[0094] 2. The synthetic composition as described in embodiment 1, wherein the lipid fraction comprises milk fat and preferably further comprises vegetable oil.

[0095] 3. The synthetic composition of any of the preceding embodiments, wherein the lipid fraction comprises long chain saturated fatty acids (LC SFA) linked to glycerol, and at least 20 mol % of the LC SFA are linked to the sn-2 position of glycerol, preferably at least 30 mol %.

[0096] The synthetic composition of any of the preceding embodiments, wherein the lipid fraction comprises saturated fatty acids (SFA) linked to glycerol, and at least 20 mol % of the SFA are linked to the sn-2 position of glycerol, preferably at least 30 mol %, more preferably at least 35 mol %, most preferably at least 41 mol %.

[0097] 5. A synthetic composition as described in any of embodiments 2-4, wherein the amount of milk fat, as measured relative to the total amount of fat in the composition, is at least 10wt%, preferably at least 20wt%, more preferably at least 30wt%, even more preferably at least 40wt%, most preferably at least 50wt%.

[0098] 6. A synthetic composition as described in any of Examples 2-5, wherein the lipid fraction further comprises vegetable oil, and wherein the amount of vegetable oil is at least 10 wt %, preferably at least 20 wt %, more preferably at least 30 wt %, most preferably at least 40 wt % as measured relative to the total amount of fat in the composition.

[0099] 7. The synthetic composition of any one of claims 2-6, wherein the milk fat is mammalian milk fat, preferably from ruminants.

[0100] 8. The synthetic composition of any preceding embodiment, wherein the protein fraction comprises goat or cow milk protein, and wherein the amount of goat or cow milk protein in the protein fraction, as determined by the amount of protein in the protein fraction, is greater than 80 wt%, preferably greater than 90 wt%.

[0101] 9. The synthetic composition of any preceding embodiment, wherein the protein fraction comprises at least 10 wt% partially hydrolyzed protein.

[0102] 10. The synthetic composition of any of the preceding embodiments, further comprising a thickener selected from the group consisting of locust bean gum (LBG), carob bean gum (CBG) and starch; preferably, wherein the amount of thickener is between 0.001 wt% and 5 wt%, more preferably between 0.01 wt% and 2.5 wt%, even more preferably between 0.1 wt% and 1.5 wt%, as determined on the dry weight of the composition.

[0103] 11. The synthetic nutritional product of any preceding embodiment, wherein the product is a complete nutritional product, preferably a neonatal food product, an IFT product, a follow-on formula (FOF) and / or a toddler formula (YCF-Jr).

[0104] 12. The synthetic nutritional product of any preceding embodiment, wherein the food product further comprises vitamins and minerals.

[0105] 13. The synthetic nutritional product of any preceding embodiment, the lipid fraction comprising one or more from the group consisting of DHA, ARA and EPA, preferably comprising DHA, ARA and EPA.

[0106] 14. The synthetic composition of any preceding embodiment for use in the treatment and / or prevention of infantile reflux.

[0107] 15. Use of the synthetic composition of any one of embodiments 1-13 for treating and / or preventing infantile reflux.

[0108] 16. Use of a composition as described in any of embodiments 1-13 for increasing the digestion of lipids into free fatty acids in the stomach, as measured by the level of free fatty acids, and an increase of at least 15% compared to an infant formula with similar macronutrient levels comprising a fat fraction consisting essentially of vegetable oils and fats; preferably, the increase in free fatty acids is at least 30%, more preferably at least 45%, most preferably at least 60%.

[0109] 17. Use of the composition of any one of embodiments 1-13 for the manufacture of a medicament for treating and / or preventing infantile reflux.

[0110] 18. Use of a composition as described in any of embodiments 1-13 for the manufacture of a medicament for increasing the digestion of lipids into free fatty acids in the stomach, as measured by the level of free fatty acids, and an increase of at least 15% compared to an infant formula with similar macronutrient levels comprising a fat fraction consisting essentially of vegetable oils and fats; preferably, the increase in free fatty acids is at least 30%, more preferably at least 45%, most preferably at least 60%.

Claims

1. A synthetic nutritional composition for use in the treatment and / or prevention of reflux in infants, the synthetic nutritional composition comprising a carbohydrate fraction, a protein fraction and a lipid fraction, wherein the amount of butyrate in the lipid fraction is at least 0.2 wt% as determined by the total amount of fatty acids in the lipid fraction; and wherein the amount of sn-1,3 linked butyrate (i.e. C4:0) is greater than 70% of the total amount of butyrate, preferably wherein the amount of sn-1,3 linked butyrate (i.e. C4:0) is greater than 80%, more preferably greater than 90%.

2. The synthetic composition for use as claimed in claim 1, wherein the lipid fraction comprises milk fat and preferably further comprises vegetable oil.

3. A synthetic composition for use as claimed in any one of the preceding claims, wherein the lipid fraction comprises long chain saturated fatty acids (LC SFA) linked to glycerol and at least 20 mol % of the LC SFA are linked to the sn-2 position of glycerol, preferably at least 30 mol %.

4. A synthetic composition for use as claimed in any one of claims 2 or 3, wherein the amount of milk fat, as measured relative to the total amount of fat in the composition, is at least 10 wt%, preferably at least 20 wt%, more preferably at least 30 wt%, even more preferably at least 40 wt%, most preferably at least 50 wt%.

5. A synthetic composition for use as claimed in any one of claims 2 to 4, wherein the lipid fraction further comprises vegetable oils and fats, and wherein the amount of vegetable oils and fats, as measured relative to the total amount of fat in the composition, is at least 10 wt%, preferably at least 20 wt%, more preferably at least 30 wt%, most preferably at least 40 wt%.

6. The synthetic composition for use as claimed in any one of claims 2 to 5, wherein the milk fat is mammalian milk fat, preferably from ruminants.

7. A synthetic composition for use as claimed in any one of the preceding claims, wherein the protein fraction comprises goat or cow milk protein and wherein the amount of goat or cow milk protein in the protein fraction as determined by the amount of protein in the protein fraction is greater than 80 wt%, preferably greater than 90 wt%.

8. The synthetic composition for use as claimed in any one of the preceding claims, wherein the protein fraction comprises at least 10 wt% of partially hydrolyzed proteins.

9. A synthetic composition for use according to any one of the preceding claims, further comprising a thickener selected from the group consisting of locust bean gum (LBG), carob bean gum (CBG) and starch; preferably, wherein the amount of thickener is between 0.001 wt% and 5 wt%, more preferably between 0.01 wt% and 2.5 wt%, even more preferably between 0.1 wt% and 1.5 wt%, as determined on the dry weight of the composition.

10. The synthetic nutritional composition for use according to any of the preceding claims, wherein the product is a complete nutritional product, preferably a neonatal food, an IFT product, a follow-on formula (FOF) and / or a toddler formula (YCF-Jr).

11. The synthetic nutritional composition for use according to any one of the preceding claims, wherein the food product further comprises vitamins and minerals.

12. The synthetic nutritional composition for use according to any of the preceding claims, wherein the lipid fraction comprises one or more from the group consisting of: DHA, ARA and EPA, preferably DHA, ARA and EPA.

13. Use of a synthetic composition as claimed in any one of claims 1 to 12 for treating and / or preventing reflux in infants, or alternatively, a synthetic composition as claimed in any one of claims 1 to 12 for use in treating and / or preventing reflux in infants.

14. Use of a composition as claimed in any one of claims 1 to 12 for increasing the digestion of lipids into free fatty acids in the stomach as measured by the level of free fatty acids and an increase of at least 15% compared to an infant formula with similar macronutrient levels comprising a fat fraction consisting essentially of vegetable oils and fats; preferably, the increase in free fatty acids is at least 30%, more preferably at least 45%, most preferably at least 60%.

15. Use of the composition according to any one of claims 1 to 12 for the manufacture of a medicament for the treatment and / or prevention of infantile reflux.

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