Food-grade butyrate

Abstract

Formula (1), (2), (3), or (4) [In the formula, R 1 , R 2 , R 3 , R 4 , R 5 , and R 6 are independently long chain fatty acids having 16 to 20 carbons] or combinations thereof to provide a source of butyrate with improved organoleptic properties. [Selection diagram] None

Description

[Technical Field]

[0001] This invention relates to a butyrate food ingredient having improved sensory stimulation properties. [Background technology]

[0002] Butyric acid salts and esters are called butyrates or butanoates. Butyric acid in ester form is found in many foods, such as milk, especially the milk of goats, sheep, cows, camels, and buffaloes, as well as milk-derived products, such as butter and cheese, such as Parmesan cheese. Butyric acid is also a product of anaerobic fermentation, such as a fermentation product produced by the gut microbiota.

[0003] Numerous beneficial effects of butyrate have been well documented in mammals and livestock. At intestinal concentrations, butyrate acts to regulate transepithelial fluid transport, mucosal inflammation, and oxidation, enhances intestinal barrier function, and influences visceral sensitivity and intestinal motility.

[0004] Butyrate has been shown to improve the structure of the intestines of piglets with short bowel syndrome (Bartholome et al., J of Parenter Enteral Nutr. 2004;28(4):210-222), and in human cell lines, it reduces the proliferation of colorectal cancer cells (Lupton, J Nutr., 2004;134(2):479-482). The production of volatile fatty acids such as butyric acid from fermentable fiber may contribute to the role of dietary fiber in colorectal cancer (Lupton, The Journal of Nutrition. 134(2):479-82). Bacteria in the colon that feed on or ferment non-digestible fiber and / or prebiotics produce short-chain fatty acids (SCFAs). Examples of SCFAs include, but are not limited to, acetic acid, propionic acid, and butyric acid. SCFAs, particularly butyrate, inhibit histone deacetylases at the Foxp3 locus, promoting the generation of regulatory T cells in the colon (Furusawa Y, et al., Nature 2013;504(7480):446-450). Oral supplementation of butyrate enhances the antibacterial activity of intestinal macrophages, limiting the spread of bacteria across the intestinal barrier. Butyrate also benefits colon cells by increasing energy production. In addition, butyrate has been shown to reduce the incidence of diarrhea (Berni Canani et al., Gastroenterol., 2004;127(2):630-634), improve gastrointestinal symptoms in individuals with diarrhea-predominant irritable bowel syndrome (Scarpellini et al., Dig Liver Dis., 2007;1(1):19-22), and enhance small intestinal growth in neonatal pigs (Kotunia et al., J Physiol Pharmacol. 2004;55(2):59-68).

[0005] Tributyrin is a triglyceride consisting of three ester functional groups each having a butyrate moiety and a glycerol backbone. Under hydrolysis conditions such as those that occur during digestion, tributyrin can serve as a source of 3 moles of butyric acid per mole of tributyrin. However, the effectiveness of tributyrin can be limited by rapid lipolysis in the stomach.

[0006] Both butyric acid and tributyrin are generally regarded as safe (GRAS) food additives (21 CFR 582.60 and 21 CFR 184.1903, respectively) and are natural components of many dairy products. However, butyric acid is associated with negative sensory qualities such as the odor characteristics of vomit, feces, and cheese. Tributyrin also has negative sensory qualities, particularly a high degree of bitterness. These unpleasant taste and odor characteristics can make oral administration of compositions containing these compounds particularly difficult, especially in pediatric populations.

[0007] Therefore, it is beneficial to provide a food-grade butyrate source having improved sensory stimulation properties compared to available solutions. The liquid form provides further advantages by virtue of ease of formulation and reduction of dissolution and homogenization problems. SUMMARY OF THE INVENTION

[0008] The present invention provides compounds having improved sensory stimulation properties and which are a source of butyric acid. In particular, the compounds have improved odor and / or taste compared to butyric acid, butyrate salts, and tributyrin. The compounds can be used as a food source of butyric acid. The compounds can be used, for example, in nutritional compositions, dietary supplements, infant formula (infant milk), and follow-on milk.

[0009] Advantageously, it has been found that the compounds of the present invention exhibit a low rate of lipolysis in the stomach and the compounds of the present invention can effect an effective delivery of butyric acid to the intestine.

[0010] According to a first aspect of the present invention, for providing a source of butyric acid or butyrate having improved sensory stimulation properties, a compound of the formula

Chemical formula

[0011] The compounds of formula (1), formula (2), formula (3), and / or formula (4) may be present in a composition such as, for example, a nutritional formulation, a dietary supplement, an infant formula, or a follow-on milk.

[0012] In one embodiment, the improved sensory stimulation property is an improved odor. In one embodiment, the improved sensory stimulation property is an improved taste. In one embodiment, the improved sensory stimulation property is an improved odor and an improved taste. In one embodiment, the improved taste is a reduced bitterness.

[0013] According to another aspect of the present invention, for providing a source of butyrate or butyric acid, a dietary supplement comprising a compound of the formula

Chemical formula

[0014] The dietary supplement may be in the form of, for example, a capsule, a tablet, a sachet, a liquid / oil, or a powder.

[0015] According to another aspect of the present invention, formula [ka] [In the formula, R 1 , R 2 , R 3 , R 4 , R 5 , and R 6 An infant formula or follow-on milk is provided, which independently contains a compound or combination thereof having a long-chain fatty acid having 16 to 20 carbon atoms.

[0016] According to another aspect of the present invention, the use of infant formula or follow-on milk of the present invention is provided to provide a source of butyrate or butyric acid having improved sensory stimulation properties.

[0017] According to another aspect of the present invention, a formula for use in improving or maintaining gastrointestinal (GI) health is [ka] [In the formula, R 1 , R 2 , R 3 , R 4 , R 5 , and R 6 A compound or combination thereof is provided, which independently has a long-chain fatty acid having 16 to 20 carbon atoms.

[0018] According to another aspect of the present invention, a method for improving or maintaining the health of a patient, comprising the formula [ka] [In the formula, R 1 , R 2 , R 3 , R 4 , R 5 , and R 6A method is provided which involves administering an effective amount of a compound or combination thereof that independently has a long-chain fatty acid having 16 to 20 carbon atoms.

[0019] In one embodiment, a combination of a compound having formula (1) and a compound having formula (2) is used as defined herein or present in a composition (e.g., a nutritional composition, a nutritional supplement, infant formula, or follow-on milk) as defined herein. Preferably, the compound having formula (1) is present in an amount of at least 10% by weight of the total triglycerides in the composition, and the compound having formula (2) is present in an amount of at least 10% by weight of the total triglycerides in the composition.

[0020] In one embodiment, a combination of a compound having formula (1) and a compound having formula (2) is used as defined herein or present in a composition (e.g., a nutritional composition, a nutritional supplement, infant formula, or follow-on milk) as defined herein, wherein the compound having formula (1) is present in an amount of at least 10% by weight of the total butyric acid-containing triglycerides in the composition, and the compound having formula (2) is present in an amount of at least 10% by weight of the total butyric acid-containing triglycerides in the composition.

[0021] In another embodiment, a combination of a compound having formula (1) and a compound having formula (2) is used as defined herein or present in a composition (e.g., a nutritional composition, a nutritional supplement, infant formula, or follow-on milk) as defined herein, wherein the compound having formula (1) is present in an amount of at least 15% by weight of the total butyric acid-containing triglycerides in the composition, and the compound having formula (2) is present in an amount of at least 15% by weight of the total butyric acid-containing triglycerides in the composition.

[0022] In one embodiment, a combination of a compound having formula (1), a compound having formula (2), a compound having formula (3), and a compound having formula (4) is used as defined herein or present in a composition as defined herein, i.e., in a nutritional composition, a nutritional supplement, infant formula, or follow-on milk.

[0023] In one embodiment, R as defined herein 1 , R 2 , R 3 , R 4 , R 5 , and / or R 6 These are unsaturated fatty acids, preferably monounsaturated ones.

[0024] In one embodiment, R as defined herein 1 , R 2 , R 3 , R 4 , R 5 , and / or R 6 This is selected from the group consisting of oleic acid, palmitic acid, stearic acid, or linoleic acid.

[0025] In one embodiment, R as defined herein 1 , R 2 , R 3 , R 4 , R 5 , and / or R 6 It is oleic acid.

[0026] In one embodiment, R as defined herein 1 , R 2 , R 3 , R 4 , R 5 , and / or R 6 It is palmitic acid.

[0027] In one embodiment, compound (1) is 1,3-dibutyryl-2-palmitoylglycerol.

[0028] In one embodiment, R 1, R 2 , R 3 , R 4 , R 5 , and / or R 6 Each of these is oleic acid.

[0029] In one embodiment, the compound having formula (1) is as follows:

[0030] [ka] In one embodiment, the compound having formula (2) is as follows:

[0031] [ka] In one embodiment, the compound having formula (3) is as follows:

[0032] [ka] In one embodiment, the compound having formula (4) is as follows:

[0033] [ka] According to another aspect of the present invention, formula [ka] A composition is provided comprising a compound having formula (5), wherein the compound having formula (5) constitutes at least 10% by weight of the total triglycerides in the composition, and the compound having formula (6) constitutes at least 10% by weight of the total triglycerides in the composition.

[0034] In one embodiment, the compound having formula (5) constitutes at least 15% by weight of the total triglycerides in the composition, and the compound having formula (6) constitutes at least 15% by weight of the total triglycerides in the composition.

[0035] In one embodiment, the compound having formula (5) constitutes at least 15% by weight of the total triglycerides in the composition, and the compound having formula (6) constitutes at least 20% by weight of the total triglycerides in the composition.

[0036] In one embodiment, the compound having formula (5) constitutes at least 20% by weight of the total triglycerides in the composition, and the compound having formula (6) constitutes at least 20% by weight of the total triglycerides in the composition.

[0037] In one embodiment, the compound having formula (5) constitutes about 15% to about 30% by weight of the total triglycerides in the composition, and the compound having formula (6) constitutes about 20% to about 30% by weight of the total triglycerides in the composition.

[0038] In one embodiment, the composition, formula [ka] The composition further comprises compounds having formula (7), preferably the compound having formula (7) constitutes at least 2% or 3% by weight of the total triglycerides in the composition, and / or formula [ka] The composition further comprises compounds having formula (8), and preferably, the compound having formula (8) constitutes at least 2% or 3% by weight of the total triglycerides in the composition.

[0039] According to another embodiment of the present invention, formula [ka] A composition is provided comprising a compound having formula (5), wherein the compound having formula (5) constitutes at least 10% by weight of the total butyrate-partially-containing triglycerides in the composition, and the compound having formula (6) constitutes at least 10% by weight of the total butyrate-partially-containing triglycerides in the composition.

[0040] In one embodiment, the compound having formula (5) constitutes at least 15% by weight of the total amount of butyrate-partially-containing triglycerides in the composition, and the compound having formula (6) constitutes at least 15% by weight of the total amount of butyrate-partially-containing triglycerides in the composition.

[0041] In one embodiment, the compound having formula (5) constitutes at least 15% by weight, preferably at least 20% by weight, of the total butyrate-containing triglycerides in the composition, and the compound having formula (6) constitutes at least 20% by weight, preferably at least 25% by weight, of the total butyrate-containing triglycerides in the composition.

[0042] In one embodiment, the composition further comprises a compound having formula (7), preferably the compound having formula (7) comprising at least 2% or 3% by weight of the total butyrate-partially-containing triglycerides in the composition, and / or the composition further comprises a compound having formula (8), preferably the compound having formula (8) comprising at least 2% or 3% by weight of the total butyrate-partially-containing triglycerides in the composition.

[0043] The compositions of the present invention are 1,3-dibutylyl-2-linoleoylglycerol, 1,3-dibutylyl-2-stearoylglycerol, 1-butyryl-2-oleoyl-3-palmitoylglycerol, 1-palmitoyl-2-oleoyl-3-butyrylglycerol, 1-butyryl-2-oleoyl-3-linoleoylglycerol, 1-linoleoyl-2-oleoyl-3-butyrylglycerol, 1-oleoyl-2-butyryl-3-oleoylglycerol, 1-butyryl-2-linoleoyl-3-oleoylglycerol , may further contain 1-oleoyl-2-linoleoyl-3-butyrylglycerol, 1-butyryl-2-stearoyl-3-oleoylglycerol, 1-oleoyl-2-stearoyl-3-butyrylglycerol, 1-butyryl-2-oleoyl-3-stearoylglycerol, 1-stearoyl-2-oleoyl-3-butyrylglycerol, 1,2-dioleoyl-3-palmitoylglycerol, 1-palmitoyl-2,3-dioleoylglycerol, 1,2-dioleoyl-3-linoleoylglycerol, and / or 1-linoleoyl-2,3-dioleoylglycerol.

[0044] The composition of the present invention may also be in the form of a nutritional composition.

[0045] The composition of the present invention may be in the form of infant formula or follow-on milk.

[0046] The composition of the present invention may also be in the form of a nutritional supplement.

[0047] According to another aspect of the present invention, the use of compositions defined herein is provided for providing a source of butyrate or butyric acid having improved sensory stimulation properties.

[0048] According to another aspect of the present invention, a method is provided for providing a source of butyric acid having improved sensory stimulation properties for a subject, comprising administering an effective amount of a composition defined herein to the subject.

[0049] According to another aspect of the present invention, compositions defined herein are provided for improving or maintaining gastrointestinal health.

[0050] According to another aspect of the present invention, a method is provided for improving or maintaining gastrointestinal health in a subject, comprising administering an effective amount of a composition as defined herein to the subject. [Brief explanation of the drawing]

[0051] [Figure 1] This shows the release of fatty acids from an emulsion containing 200 mg of (A) triptyline, (B) high-oleic sunflower oil, and (C) a mixture of butyrate-partially-containing triacylglycerol (TAG) according to the present invention. The mixture is digested either i) in simulated intestinal fluid (SIF) or (ii) sequentially in simulated intestinal fluid (SIF) following gastric juice (SGF). [Figure 2] This shows the overall degree of lipid digestion of a mixture of triptyline, high-oleic sunflower oil, and the butyrate-containing TAG according to the present invention after both SIF and SGF-SIF. [Modes for carrying out the invention]

[0052] Triglycerides Triglycerides (also called triacylglycerols) are triesters derived from glycerol and three fatty acids.

[0053] Fatty acids are carboxylic acids that have a long tail (chain). Fatty acids can be either unsaturated or saturated. Fatty acids that are not bound to other molecules are called free fatty acids (FFAs).

[0054] The term "fatty acid portion" refers to the portion of the triglyceride derived from a fatty acid in the esterification reaction with glycerol. The triglycerides used in this invention include at least one butyric acid portion and at least one long-chain fatty acid portion.

[0055] The long-chain fatty acids preferred for use in this invention are fatty acids having 16 to 20 carbon atoms.

[0056] Examples of long-chain fatty acids include oleic acid, palmitic acid, stearic acid, and linoleic acid.

[0057] The triglycerides of the present invention can be synthesized, for example, by esterification of long-chain fatty acids and butyric acid with glycerol.

[0058] The triglycerides of the present invention can be synthesized, for example, by transesterification between triptyline and another triglyceride containing long-chain fatty acids. In one embodiment, high-oleic sunflower oil is used as the raw material for the long-chain fatty acids. This produces a triglyceride mainly containing a butyrate moiety and an oleate moiety. Oleic acid is the main fatty acid found in breast milk. This compound is free of milk components, cholesterol, and animal-derived components. Fatty acids are detached from the triglycerides in the gastrointestinal tract by naturally occurring lipases. Compared to butyrate salts, this compound does not require the addition of further mineral salts to the final formulation.

[0059] Alternative methods for triglyceride synthesis can be determined by those skilled in the art as part of the usual procedure. As an example, a method for obtaining 1,3-dibutyryl-2-palmitoylglycerol (BPB) is shown below.

[0060] [ka] A single butyrate-partially-containing triglyceride may be used herein. Alternatively, a mixture of different butyrate-partially-containing triglycerides may be used.

[0061] composition The present invention provides compositions comprising a butyrate-partially-containing triglyceride as referred to herein. The compositions may be, for example, nutritional compositions, nutritional supplements, infant formulas, or follow-on milks.

[0062] The term "nutritional composition" means a composition that provides nutrition to a subject. This nutritional composition is preferably taken orally and may contain lipids, or fat sources and protein sources. Such a composition may also contain carbohydrate sources. In one embodiment, the nutritional composition contains only lipids or fat sources. In other specific embodiments, the nutritional composition contains lipid (or fat) sources together with protein sources, carbohydrate sources, or all of these.

[0063] In some specific embodiments, the nutritional composition according to the present invention is an "enteral nutrition composition," i.e., a food product in which the gastrointestinal tract is involved in the administration of the composition. Introduction into the stomach may involve the use of a tube that leads directly to the stomach through the oral / nasal passage or the abdominal cavity. Such a tube can be used particularly in hospitals or clinics.

[0064] The composition according to the present invention may be an infant formula (e.g., infant starter formula), follow-up milk or follow-on milk, growing-up milk, baby food, infant cereal composition, fortifiers such as breast milk fortifiers, or nutritional supplements.

[0065] As used herein, the expression "infant formula" refers to a food intended for specific nutritional supplementation purposes for infants during the first month of life, which, by itself, satisfies the nutritional requirements for infants in this category (e.g., Article 2(c) of the European Commission Directive 91 / 321 / EEC 2006 / 141 / EC of 22 December 2006, for infant formula and follow-on milk).

[0066] Generally, starter formula is a breast milk substitute for infants after birth. Follow-up formula or follow-on formula is given from 6 months of age onward. These formulas constitute the main liquid component in the increasingly diverse diet of infants in this category. "Growing-up formula" (or GUM) is given from 1 year of age onward. This formula is generally a dairy beverage specifically formulated to meet the nutritional needs of children.

[0067] The term "fortifier" refers to a liquid or solid nutritional composition suitable for mixing with breast milk (human milk) or infant formula. The term "breast milk" should be understood as the mother's milk or colostrum, or the donor's milk or colostrum from the donor's milk.

[0068] The term “nutritional supplement” can be used as something that complements an individual’s nutrition (typically used for nutritional supplementation, but also as an addition to any kind of composition intended for ingestion). This may be, for example, in the form of tablets, capsules, lozenges, or liquids. Nutritional supplements may further contain protective hydrophilic colloids (such as gums, proteins, modified starches), binders, membrane-forming agents, encapsulating agents / materials, wall / shell materials, matrix compounds, coatings, emulsifiers, surfactants, solubilizers (such as oils, fats, waxes, lecithins), adsorbents, carriers, fillers, co-compounds, dispersants, wetting agents, processing aids (solvents), flowing agents, taste masking agents, bulking agents, gelling agents, and gelling agents. Dietary supplements may also contain conventional pharmaceutical additives and adjuvants, excipients, and diluents, including, but not limited to, water, gelatin of any origin, vegetable gum, lignin sulfonate, talc, sugar, starch, gum arabic, vegetable oil, polyalkylene glycol, flavoring agents, preservatives, stabilizers, emulsifiers, buffers, lubricants, colorants, wetting agents, and fillers.

[0069] In another specific embodiment, the nutritional composition of the present invention is a fortifier. The fortifier may be a breast milk fortifier or a formula fortifier such as an infant formula fortifier. Therefore, if the infant or toddler is premature, the fortifier is a particularly advantageous embodiment.

[0070] If the composition is a nutritional supplement, it can be provided in the form of a unit dose.

[0071] The nutritional compositions of the present invention, particularly infant formula, generally contain a protein source, a carbohydrate source, and a lipid source. However, in some embodiments, particularly when the nutritional composition of the present invention is a nutritional supplement or fortifier, only lipids (or a lipid source) may be present.

[0072] The nutritional composition according to the present invention may contain a protein source. The amount of protein may be 1.6 to 3 g / 100 kcal. In some embodiments, particularly when the composition is intended for premature infants / toddlers, the amount of protein may be 2.4 to 4 g / 100 kcal, or more than 3.6 g / 100 kcal. In some other embodiments, the amount of protein may be less than 2.0 g / 100 kcal, for example, 1.8 to 2 g / 100 kcal, or less than 1.8 g / 100 kcal.

[0073] For example, protein sources based on whey, casein, and mixtures thereof can be used in the same way as plant-based protein sources, such as soybeans. With respect to whey protein, the protein source may be based on acidic whey, sweet whey, or mixtures thereof, and may contain α-lactalbumin and β-lactoglobulin in any desired proportion. In some embodiments, the primary protein source is whey (i.e., more than 50%, for example, more than 60% or more than 70% of the protein is derived from whey protein). The protein may be intact protein, hydrolyzed protein, or a mixture of intact and hydrolyzed protein. The term “intact” means that the main portion of the protein is intact, i.e., its molecular structure remains unchanged, for example, at least 80% of the protein remains unchanged, for example, at least 85% of the protein remains unchanged, preferably at least 90% of the protein remains unchanged, and more preferably at least 95% of the protein remains unchanged, for example, at least 98% of the protein remains unchanged. In certain embodiments, the protein is completely unchanged.

[0074] In the context of this invention, the term "hydrolyzed" means that a protein has been hydrolyzed, or broken down to its constituent amino acids.

[0075] The protein may be either completely hydrolyzed or partially hydrolyzed. If hydrolyzed protein is required, the hydrolysis step may be carried out as desired, as known in the art. For example, a hydrolyzed whey protein can be prepared by enzymatically hydrolyzing a whey fraction in one or more steps. It has been found that if the whey fraction used as a starting material is substantially lactose-free, the protein undergoes significantly less lysine blackage during the hydrolysis step. This can reduce the degree of lysine blackage from about 15% by weight of total lysine to less than about 10% by weight of total lysine, for example, with about 7% by weight of lysine, the nutritional value of the protein source is significantly improved.

[0076] In a particular embodiment, the protein in the composition is hydrolyzed, completely hydrolyzed, or partially hydrolyzed. The degree of hydrolysis (DH) of the protein may be 2 to 20, or 8 to 40, or 20 to 60, or 20 to 80, or greater than 10, greater than 20, greater than 40, greater than 60, greater than 80, or greater than 90. For example, a nutritional composition containing a hydrolysate having a degree of hydrolysis of less than about 15% is commercially available from Nestle Company under the trademark name Peptamen®.

[0077] At least 70%, 80%, 85%, 90%, 95%, or 97% of the protein may be hydrolyzed. In certain embodiments, 100% of the protein is hydrolyzed.

[0078] In one particular embodiment, the protein of the composition is a plant-derived protein.

[0079] The nutritional composition according to the present invention may contain a carbohydrate source. This is particularly preferred when the nutritional composition of the present invention is infant formula. In this case, any carbohydrate source commonly found in infant formula, such as lactose, sucrose, maltodextrin, starch, and mixtures thereof, can be used, but one preferred carbohydrate source for infant formula is lactose. The nutritional composition of the present invention may also contain all vitamins and minerals that are understood to be essential in the daily diet and in nutritionally significant amounts. Minimum requirements for specific vitamins and minerals have been established. Examples of minerals, vitamins, and other nutrients optionally present in the composition of the present invention include vitamin A, vitamin B1, vitamin B2, vitamin B3, vitamin B6, vitamin B12, vitamin E, vitamin K, vitamin C, vitamin D, folic acid, inositol, niacin, biotin, pantothenic acid, choline, calcium, phosphorus, iodine, iron, magnesium, copper, zinc, manganese, chlorine, potassium, sodium, selenium, chromium, molybdenum, taurine, and L-carnitine. Minerals are usually added in salt form. The presence and amount of specific minerals and other vitamins will vary depending on the target population. If necessary, the nutritional composition of the present invention may also contain emulsifiers and stabilizers, such as soy, lecithin, and citrate esters of mono and diglycerides. The nutritional composition of the present invention may also contain other substances that may have beneficial effects, such as lactoferrin, osteopontin, TGFβ, slgA, glutamine, nucleotides, and nucleosides.

[0080] The composition of the present invention may further contain at least one indigestible oligosaccharide (e.g., a prebiotic). These are typically present in an amount of 0.3 to 10% by weight of the composition.

[0081] Prebiotics are typically indigestible, meaning they are not broken down and absorbed in the stomach or small intestine. Therefore, prebiotics remain intact when they enter the large intestine, where they are selectively fermented by beneficial bacteria. Examples of prebiotics include certain oligosaccharides such as fructooligosaccharides (FOS), inulin, xylooligosaccharides (XOS), polydextrose, or any mixture thereof. In certain embodiments, the prebiotics may be fructooligosaccharides and / or inulin. In certain embodiments, the prebiotics may be a combination of FOS and inulin, for example, the combination found in products marketed by BENEO-Orafti under the trademark name Orafti® Oligofructose (formerly Raftilose®), or the combination found in products marketed by BENEO-Orafti under the trademark name Orafti® Inulin (formerly Raftiline®). Another example is a combination of 70% short-chain fructooligosaccharides and 30% inulin, which is registered by Nestle under the trademark name "Prebio1". The nutritional compositions of the present invention may also contain at least one milk oligosaccharide, which may be BMO (milk oligosaccharide) and / or HMO (human milk oligosaccharide). The compositions of the present invention may further contain at least one probiotic (i.e., a probiotic strain), such as a probiotic strain.

[0082] The most commonly used probiotic microorganisms are mainly bacteria and yeasts of the following genera: Lactobacillus spp., Streptococcus spp., Enterococcus spp., Bifidobacterium spp., and Saccharomyces spp.

[0083] In some specific embodiments, the probiotic is a probiotic strain. In some specific embodiments, the probiotic strain is Bifidobacterium and / or Lactobacillus.

[0084] The nutritional composition according to the present invention may contain, on a dry weight basis, 10 e3 to 10 e12 cfu of probiotic strains per gram of composition, more preferably 10 e7 to 10 e12 cfu, for example, 10 e8 to 10 e10 cfu of probiotic strains.

[0085] In one embodiment, the probiotics are viable. In another embodiment, the probiotics are non-replicating or inactivated. The probiotics may also be a portion of the probiotic, such as a cell wall component, or a metabolite of the probiotic. In some other embodiments, both viable and inactivated probiotics may be present. The nutritional composition of the present invention may further include at least one phage (bacteriophage) or mixture of phages, preferably against pathogenic streptococci, Haemophilus, Moraxella, and Staphylococcus.

[0086] In one embodiment, the nutritional composition according to the present invention may be a dairy product. A dairy product is a product containing dairy products. Dairy products are generally made from a suitable mixture of concentrated milk protein and a fat source. Dairy products can be acidified. Examples of dairy products include ready-to-drink dairy beverages, concentrated milk, evaporated milk, sweetened concentrated milk, milk powder, yogurt, fresh cheese, cheese, ice cream, and dairy spreads, such as spreadable fresh cheese, cottage cheese, quark, crème fraîche, clotted cream, and cream cheese. Milk powder can be produced, for example, by spray drying or freeze-drying.

[0087] Depending on the fat content, dairy products can be prepared from whole milk, whole milk, semi-skimmed milk, skim milk, or low-fat milk. Skim milk is milk containing less than 0.1% milk fat. Semi-skimmed milk contains 1.5% to 2.5% milk fat. Whole milk typically contains 3% to 4% fat. The exact fat content of skim milk, semi-skimmed milk, and whole milk varies mainly depending on local food regulations.

[0088] Dairy products are generally made from cow's milk. Dairy products can also be made from buffalo milk, yak milk, goat milk, sheep's milk, mare's milk, donkey's milk, camel's milk, reindeer's milk, moose's milk, or combinations thereof.

[0089] Acidified dairy products can be obtained by fermentation using suitable microorganisms. Fermentation imparts flavor and acidity to dairy products. Fermentation may also affect the texture of dairy products. In addition, the microorganisms used for fermentation are selected based on their ability to ferment milk into edible fermented dairy products. Typically, these microorganisms are known for their beneficial properties. Examples of such microorganisms include lactic acid bacteria and yeasts. Some of these microorganisms can be considered probiotics. Examples of lactic acid bacteria include Lactobacillus delbrueckii subspecies bulgaricus and Streptococcus thermophilus, both of which are involved in the production of yogurt, or other lactic acid bacteria belonging to the genera Lactobacillus, Streptococcus, Lactococcus, Leuconostoc, Bifidobacterium, Pediococcus, or any mixture thereof.

[0090] Another example of fermented dairy products, also called cultured dairy products or cultured dairy foods, or cultured milk, is fermented buttermilk fermented with Lactococcus lactis (Lactococcus lactis subgenus Lactococcus lactis, Lactococcus lactis subgenus Cremoris, Lactococcus lactis subgenus Lactococcus viover diacetylactis) and / or Leuconostoc mesenteroides subgenus Cremoris.

[0091] The microorganisms can be alive or inactive.

[0092] Dairy-like products are products manufactured in the same manner as the dairy products described above, but using (all or part) protein sources other than milk, and / or (all or part) edible fat sources other than milk. Suitable protein sources include plant proteins, such as soybeans, potatoes, and peas. Suitable fat sources include oils and fats of plant or marine origin. Fats and oils are used as interchangeable terms. Since the separation step can be omitted depending on the formulation of the dairy-like product, preparation in the same manner as described above means product processing in which the conventional whey separation step is omitted.

[0093] The nutritional composition according to the present invention can be prepared by any suitable method.

[0094] For example, infant formula can be prepared by blending a protein source, a carbohydrate source, and a fat source in appropriate proportions. If used, emulsifiers can be added at this stage. Vitamins and minerals may be added at this stage, but are usually added later to avoid thermal decomposition. Any lipophilic vitamins and emulsifiers can be dissolved in the fat source before blending. Then, preferably, reverse osmosis treated water can be mixed in to form a liquid mixture. The water temperature should be in the range of about 50°C to about 80°C, as appropriate, to aid in the dispersion of the components. A commercially available liquefaction device can be used to form the liquid mixture.

[0095] In particular, if the final product is in liquid form, any oligosaccharide can be added at this stage. Similarly, if the final product is in powder form, any oligosaccharide can be added at this stage if desired.

[0096] Next, the liquid mixture is homogenized, for example, in two steps.

[0097] In one embodiment, the nutritional composition of the present invention is given to an infant or toddler as a nutritional supplement composition for breast milk.

[0098] The composition of the present invention may be in the form of, for example, a solid (e.g., powder), a liquid, or a gelatinous substance.

[0099] The compositions of the present invention may be, for example, tablets, sugar-coated tablets, capsules, gel caps, powders, granules, solutions, emulsions, suspensions, coated particles, spray-dried particles, or pills.

[0100] The composition may be in the form of a pharmaceutical composition and may contain one or more suitable pharmaceutically acceptable carriers, diluents, and / or excipients.

[0101] Examples of such excipients suitable for the compositions described herein can be found in "Handbook of Pharmaceutical Excipients," 2nd Edition, (1994), edited by A. Wade and P.J. Weller.

[0102] Carriers or diluents acceptable for therapeutic use are known in the pharmaceutical field and are described, for example, in Remington's Pharmaceutical Sciences, Mack Publishing Co. (ARGennaro edit. 1985).

[0103] The pharmaceutical composition may contain, or in addition to, any suitable binder, lubricant, suspending agent, coating agent, and / or solubilizer as a carrier, excipient, or diluent. Examples of suitable binders include starch, gelatin, natural sugars such as glucose, anhydrous lactose, fluid lactose, and β-lactose, corn sweeteners, natural and synthetic gums such as acacia, tragacanth, or sodium alginate, carboxymethylcellulose, and polyethylene glycol.

[0104] Examples of suitable lubricants include sodium oleate, sodium stearate, magnesium stearate, sodium benzoate, sodium acetate, and sodium chloride.

[0105] Preservatives, stabilizers, dyes, and even flavorings may be included in the composition. Examples of preservatives include sodium benzoate, sorbic acid, and esters of p-hydroxybenzoic acid. Antioxidants and suspending agents may also be used.

[0106] Gastrointestinal health The compounds defined herein are butyrate / butyric acid precursors and can therefore be used to improve or maintain gastrointestinal (GI) health.

[0107] In one embodiment, the compounds and compositions defined herein can be used for the treatment of inflammatory bowel diseases, such as Crohn's disease or ulcerative colitis.

[0108] Butyrate has been well documented for its numerous beneficial effects on GI health. At intestinal concentrations, butyrate acts to regulate transepithelial fluid transport, mucosal inflammation, and oxidation, strengthening the epithelial barrier, and regulating visceral sensitivity and intestinal motility.

[0109] Butyrate-containing fatty acids are the primary energy source for colonic mucosal cells (Roedriger, Gut. 1980;21:793-798) and are most important for colonic cells in the distal region of the colon. The potent nutritional effects of butyrate on the mucosa of the small intestine have been observed in experimental animals (Guilloteau et al., 2 J Anim Feed Sci. 2004;13, Suppl. 1:393-396). A decrease in intestinal butyrate concentration leads to atrophy of the colonic mucosa, which is usually explained by a decrease in the usefulness of the substrate to colonic cells. On the other hand, administration of butyrate into the colonic lumen induces weight gain, increased DNA synthesis, and deeper intestinal crypts (Kripke et al., J Parenter Enter Nutr. 1989;13:109-116).

[0110] High concentrations of butyrate, obtained by fermentation of insoluble dietary fiber or after rectal administration of butyrate, can inhibit early and advanced colorectal cancer development by regulating the transcription, expression, and activation of key proteins in the apoptosis cascade (Avivi-Green et al., J Nutr..2002;132(7):1812-18).

[0111] Chapman et al. (Gut 1994;35(1):73-76). Inflamed colonic mucosa has been shown to capture far more butyrates than glutamine or glucose.

[0112] Experiments have shown that injection of butyrate significantly reduces inflammation and the degree of colonic wall ulcers in rats (Andoh et al., J Parenter Enter Nutr. 1999;23(5):70-73).

[0113] The effectiveness of butyrate enemas has been demonstrated through clinical observations in patients with ulcerative colitis (Han et al., Gastroenterol Clin North Am. 1999;28:423-443; Scheppach et al., Gastroenterol Suppl. 1997;222:53-57).

[0114] The direct anti-inflammatory activity of butyrate can be linked to the inhibition of nuclear factor kappa B (NFKB) translocation and the binding of butyrate to DNA, and by the same evidence, it can be linked to the inhibition of transcription and production of inflammatory cytokines (Segain et al., Gut. 2000;47:397-403).

[0115] Therefore, the triglyceride compounds used in this invention, which are the raw materials for butyrate, can play a significant role in maintaining intestinal homeostasis and GI health.

[0116] Administration Preferably, the compounds and compositions described herein are administered enterally.

[0117] Enteral administration may be, for example, oral or gastric.

[0118] Generally speaking, the administration of the combinations or compositions described herein may be, for example, administered orally or via another route into the gastrointestinal tract, and may also be administered by enteral nutrition.

[0119] The subject may be mammals such as humans, dogs, cats, horses, goats, cattle, sheep, pigs, deer, and primates. Preferably, the subject is humans. [Examples]

[0120] Example 1. Preparation of a butyrate-containing triglyceride A composition containing a butyrate-containing triglyceride was prepared by chemical transesterification between triptyline and high-oleic sunflower oil in the presence of a catalyst such as sodium methylate. Tributylline was used in a molar excess compared to high-oleic sunflower oil.

[0121] Three reagents, namely triptyline, high-oleic sunflower oil, and a catalyst, were mixed in a reactor under a nitrogen atmosphere and then heated at 80°C for 3 hours with stirring. After the reaction was complete, the product was washed with water and dried under vacuum (25 mBar, 60°C for 2 hours). The resulting oil product was then subjected to a decolorization step using bleaching clay and purified by either short-stroke distillation (130°C, 0.001-0.003 mBar) and / or deodorization by steam-water injection (160°C, 2 mBar, 2 hours).

[0122] Table 1 below shows the components of the obtained oil composition (mostly triglycerides). These triglycerides are represented by the three fatty acids they contain. These fatty acids are represented by their lipid number: 4:0 for butyrate, 16:0 for palmitate, 18:0 for stearate, 18:1 for oleate, and 18:2 for linoleate. The central fatty acid is located at the sn-2 position of the triglyceride. For example, 16:0-4:0-18:1 represents two different triglycerides, each containing either a molecule with butyrate at the sn-2 position and palmitate at the sn-1 position and oleate at the sn-3 position, or oleate at the sn-1 position and palmitate at the sn-3 position.

[0123] Triglyceride profiles and positional isomers were analyzed by liquid chromatography connected to a high-resolution mass spectrometer. The proportion of each lipid was evaluated by liquid chromatography connected to an evaporative light scattering detector (ELSD).

[0124] [Table 1] In the composition sample, the two most abundant triglycerides are 4:0-18:1-4:0 and 18:1-18:1-4:0, which together amount to approximately 40-50g / 100g.

[0125] Example 2. Odor characteristics of a butyrate-containing triglyceride In the odor comparison of solutions containing butyrate-containing triglycerides (mainly composed of oleic acid and butyric acid fatty acids), the solutions were compared with those containing sodium butyrate.

[0126] Sample preparation Solutions containing butyrate-partially-containing triglycerides (see Example 1) or sodium butyrate were prepared and stored at 4°C until delivered to the sensory evaluation panelists. Each 250 mL solution contained 600 mg of butyric acid (equivalent to one capsule of commercially available sodium butyrate as a dietary supplement, at a concentration of 2.4 mg / mL) and 1% by weight / volume of BEBA Optipro1 infant formula in acidified deionized water.

[0127] Samples were prepared the day before the test by placing 4 mL of each solution (triglyceride butyrate solution and sodium butyrate solution) into Agilent vials.

[0128] method A "2-to-5 test" was conducted. In this test, five samples were presented to a panelist. The panelist was instructed to identify two samples that were different from the other three. To avoid bias due to the order of presentation, the order in which the samples were presented was randomized.

[0129] In addition to the 2-to-5 scoring test, panelists were presented with comment boxes and asked to comment on the nature of the perceived differences (e.g., odor intensity, odor quality).

[0130] result Five samples were presented to the panelists simultaneously. The panelists were asked to remove the caps in a predetermined order, smell the samples, and then recap each vial. The results are shown in Table 2.

[0131] [Table 2] The p-value was calculated using a binomial test performed with Fizz software (Biosystems, France).

[0132] According to a panelist who was able to distinguish between the correct response (a butyrate-containing TAG sample that differs from sodium butyrate), sodium butyrate had a "cheese" smell, while the butyrate-containing TAG sample had a significantly reduced "cheese" smell and was described as having almost no distinctive odor.

[0133] Example 3. Taste characteristics of butyrate-containing triglycerides Functional benchmarking of a solution containing a butyrate-containing triglyceride (see Example 1), mainly composed of oleic acid and butyric acid fatty acids, was performed against a solution containing triptyline.

[0134] Sample preparation One tablespoon (4.6g) of BEBA Optipro1 infant formula was added to warm water (boiled water cooled according to the instructions) to a final volume of 150mL (approximately 3 wt / vol% solution). Each triglyceride form of butyrate was weighed separately, and 600mg of butyrate was supplied. Infant formula was then added to each solution to a final volume of 50mL.

[0135] Solution A contained a butyrate-containing triglyceride (see Example 1). Solution B contained triptyline.

[0136] method The group of panelists repeatedly conducted tastings without knowing the contents.

[0137] The samples were prepared immediately before the preliminary bitterness evaluation, and each solution was vigorously shaken. Small amounts of each solution were simultaneously filled into tasting cups labeled A and B.

[0138] Two samples were presented to the panelists simultaneously. The panelists were asked to taste the solutions by taking a sip and spitting them out, and to rate the perceived bitterness on a scale of 0 to 10 (0 representing no bitterness perceived, and 10 representing the highest level of bitterness imaginable).

[0139] result Regarding the bitterness of solution A, the panelists rated it as 4.33 ± 1.52, on a mean ± standard deviation.

[0140] Regarding the bitterness of solution B, the panelists rated it as 8.33 ± 1.52, on a mean ± standard deviation.

[0141] These data indicate that, in infant formula, the butyrate-containing TAG composition exhibited significantly less bitterness in taste compared to triptyline.

[0142] Example 4. Taste characteristics of 1,3-dibutyryl-2-palmitoylglycerol 1,3-Dibutyryl-2-palmitoylglycerol (BPB) was synthesized as a single compound using the following synthesis method.

[0143] [ka] When BPB was evaluated by sensory panelists using descriptive evaluation, it was found to have no unpleasant taste or smell.

[0144] Example 5. Digestion of a butyrate-containing triglyceride 5.1.Materials Sodium taurocholate, sodium chloride, hydrochloric acid, sodium hydroxide, potassium hydroxide, maleic acid, tris(hydroxymethyl)aminomethane, pepsin (Porcine, 800-111 2500 U / mg, P7000, actual activity used 674 U / mg and 561 U / mg), pancreatin (Porcine, USP×8, P7585), and porcine bile extract (total bile salt content = 49% by weight; containing 10-15% glycodeoxycholic acid, 3-9% taurodeoxycholic acid, and 0.5-7% deoxycholic acid; 5% phospholipids, B8631) were used as obtained and purchased from Sigma-Aldrich (St Louis, MO, USA). Rabbit stomach extract (RGE 70 ≥ 70 U / mL RGL, and ≥ 280 U / mL pepsin) was purchased from Lipolytech (Marseille, France). All water used in this test was purified MilliQ quality. Tributyline was from Sigma (food grade), and high-oleic sunflower oil was from Florin. The transesterified triglycerides were obtained by chemical transesterification using sodium methylate (from Evonik) as a catalyst.

[0145] 5.2. Emulsion Preparation Polyoxyethylene sorbitan monooleate (Tween® 80) was mixed with the oil phase at 40°C, and then mixed with the aqueous phase using a magnetic stirrer to prepare a 10% by weight oil-in-water emulsion stabilized with 0.3% by weight of Tween 80. The emulsion was then prepared using a Hielscher UP400S ultrasonic probe homogenizer equipped with a 5 mm diameter rod-shaped probe by applying 100% amplitude at 100% cycle for 2 minutes, during which time the sample was cooled with ice water.

[0146] 5.3. Particle Size Measurement The droplet size of each lipid emulsion was measured by laser light scattering using a Mastersizer3000 equipped with a Hydro SM manufactured by Malvern Instruments (Malvern, Worcestershire, United Kingdom). The laser specifications of the two lasers were 4 mW, 632.8 nm and 10 mW, 470 nm. To avoid multiple scattering effects, the samples were diluted to approximately 0.002 wt%. Information on emulsion particle size was then obtained by the best agreement between the theoretical light scattering (Mie) and the measured particle size distribution. A refractive index of 1.456 and an absorption of 0.01 were used for the oil phase. The emulsion particle size was estimated as two values: the volume-surface mean diameter D3.2 (D3.2 1 / 4 Pnidi 3 / nidi 2) or the volume-length mean diameter D4.3 (D4.3 1 / 4 Pnidi 4 / nidi 3). The average of three measurements of two newly prepared emulsions is used as the result for the emulsion particle size.

[0147] 5.4.Statistical analysis Statistical analysis was performed using a two-sided t-test with unequal variances, employing the Igor Pro software.

[0148] 5.5. Digestion in vitro A lipid emulsion (2 mL) containing 200 mg of fat was subjected to in vitro gastrointestinal lipolysis. Digestion was performed in a thermostat-equipped glass container (37°C) in a pH-STAT assembly controlled by a TIM 856 bi-burette pH-STAT (Radiometer Analytical (France)). For gastric digestion, the sample was incubated with 8.5 mL of simulated gastric juice (SGF) consisting of 150 mM NaCl, 450 U / mL pepsin, and 18 U / mL rabbit gastric lipase at 37°C and pH 5.5 for 90 minutes. Digestion was initiated by adding 18 U / mL of rabbit gastric lipase (value evaluated at pH 5.4 for activity against TBU, triplutylline).

[0149] Enteral digestion was performed in pH-STAT, and the pH was kept constant at 6.8 by adding NaOH (0.05M). Bile salt mixture (bile salt prepared with Tris buffer, 5 mM Tris, and 150 mM NaCl) and calcium solution (20 mM Ca, 176 5 mM Tris, 150 mM NaCl) were added to the SGF sample mixture. This mixture was transferred to pH-STAT and the pH was adjusted to approximately 6.78. When the temperature reached 37±0.5℃, the enteral digestion step was started. The pH was adjusted to 6.8, and after incubation at this pH and temperature for 2 minutes, pancreatin solution (5 mM Tris, 150 mM NaCl, pH 6.8) was added. The final composition of the enteric fluid was 10 mM CaCl2, 12 mM mixed bile salts, 0.75 mM phospholipids, 150 mM NaCl, and 4 mM tris(hydroxymethyl)aminomethane buffer. The enteric digestion step was performed for 3 hours using a Radiometer titration manager. During the enteric digestion stage, the digestion rate was tracked using the pH-STAT (TIM856, Radiometer) method and expressed as titrable acids (not fatty acids) calculated by the following formula.

[0150] TA=V NaOH × 0:05 × 1000 TA: Total amount of titrable acid released, mmol, V NaOH : The volume of NaOH used to titrate the acid released within 3 hours, in mL.

[0151] 5.6.Results Since both gastric and intestinal lipases are involved in the digestion of dietary lipids, lipid digestibility was evaluated using two digestion models: i) simulated intestinal fluid (SIF) mediated by porcine pancreatic lipase (PPL), and ii) sequential digestion of simulated gastric fluid (SGF) mediated by rabbit gastric lipase (RGL) followed by simulated intestinal fluid (SIF) mediated by porcine pancreatic lipase (PPL). All lipids underwent emulsification with polyoxyethylene sorbitan monooleate (Tween® 80) and exhibited similar particle size distributions and specific surface areas (Figure 2). This suggests that the differences in digestion mainly stem from the molecular structure of triglycerides.

[0152] Figures 1A-Ci) show the digestion (SIF model) of the butyrate-containing triglyceride "C4-C18:1" according to the present invention, prepared by chemical transesterification between tributyline (C4), high-oleic sunflower oil (HOSFO, mostly C18:1), and tributyline and high-oleic sunflower oil (see Example 1), by porcine pancreatic lipase (spleen-derived) in the presence of mixed bile and calcium. The lipids generally exhibited similar lipolysis behavior, with an initial rapid lipolysis period in the first 15 minutes, which gradually slowed down during the last 2.5 hours of simulated enteral digestion. The C4 triglyceride showed an initial maximum lipolysis rate of 223 ± 59 μmol / min. The initial degradation rate with high-oleic sunflower oil, 34.5 ± 2.3 μmol / min, was significantly lower than that of the short-chain triglycerides (p<0.0001). C4-C18:1 showed an initial hydrolysis rate of 153 ± 47 μmol / min between C4 and C18:1. Overall, it can be seen that all triglycerides are rapidly and sufficiently digested in the presence of porcine pancreatic lipase.

[0153] Next, these triglycerides were digested using a continuous SGF(RGL)SIF(PPL) model. Digestion in the SIF portion is shown in Figure 1A-C, ii). Measurements were not performed in the stomach region due to the limited ionization of the target fatty acids. Compared to digestion with SIF alone, the titratable acid released by C4 and C18:1 triglycerides during 3 hours of digestion was generally small. The effect was greatest with triptyline, which had a significantly lower initial lipolysis rate of 44.1±8.8 μmol / min during SGF-SIF digestion compared to 223±59 μmol / min with SIF alone (p<0.0001). The total amount of acid released after SGF-SIF digestion of triptyline, 381±20 μmol, was approximately 1 / 3 of the amount released after digestion with SIF alone, 958±12.5 μmol. These results clearly indicate that the digestion of triptyline in the model's stomach is substantial.

[0154] When exposed to SGF and SIF consecutively, the SIF lipolysis rate of the butyrate-containing triglyceride C4-C18:1 was 124±20 μmol / min, showing a slight, but not statistically significant, decrease compared to SIF alone (124±20 μmol / min). Most interestingly, the secondary fatty acid chain length influenced the decrease in SIF lipolysis caused by prior exposure to RGL. Originally, with triphiline, the total fatty acid release during SIF lipolysis decreased by 60.2% (147±7.6 μmol) after prior exposure to RGL in SGF. In comparison, the C4-C18:1 transesterified triglyceride showed a decrease of 6.1% (45±7.6 μmol).

[0155] Figure 2 shows the overall degree of lipid digestion after both SIF and SGF-SIF for three triglycerides, using direct and back titrations. Many fatty acids are only partially ionized at pH 6.8, and direct titration only provides a partial picture of the degree of lipid digestion. Therefore, to estimate the overall degree of digestion, back titration up to pH 11.5 or GC-FAME analysis is required. The results of back titrations for the three triglycerides show that the tributyline and butyrate-containing triglycerides C4-C18:1 were digested by 101.5±0.9% and 101±1.6%, respectively, indicating that complete digestion releases three fatty acids per molecule. On the other hand, high-oleic sunflower oil was digested by 72.3±2%, indicating that complete digestion releases two fatty acids per molecule.

[0156] In general, triptyline was found to be fully hydrolyzed in the stomach, while high-oleic sunflower oil triglycerides were hydrolyzed very only to a limited extent. Surprisingly, butyrate-partially-containing triglycerides prepared by C4 transesterification with long-chain fatty acids (C4-C18:1) were found to reduce the degree of gastric lipolysis of C4 fatty acids. Approximately 60% of triptyline was lipolytically-mediated by gastric lipase, as indicated by the decrease in total fatty acid release during SIF lipolysis after prior exposure to RGL in SGF. In comparison, C4-C18:1 butyrate-partially-containing triglycerides showed only a 6.1% decrease in total fatty acid release in SGF-SIF. These results suggest that transesterification of C4 by long-chain fatty acids (C4-C18:1) delays and regulates the release of butyrate, causing it to be released in the intestines after digestion rather than in the stomach. Furthermore, lipid designs that incorporate this structure alter the timing (but not the degree) of delivery of short-chain fatty acids to the gastrointestinal tract.

Claims

1. To provide a source of butyrate with improved sensory stimulation properties, formula 【Chemistry 1】 [In the formula, R １ , R ２ , R ３ , R ４ , R ５ , and R ６ Infant formula or follow-on milk comprising a combination of compounds having independently an acyl group of a long-chain fatty acid having 16 to 20 carbon atoms, An infant formula or follow-on milk in which a combination of a compound having formula (1) and a compound having formula (2) is used, wherein the combination is present in a composition containing the compound having formula (1) in an amount of at least 10% by weight of the total amount of butyrate group-containing triglycerides, and the compound having formula (2) in an amount of at least 10% by weight of the total amount of butyrate group-containing triglycerides.

2. The infant formula or follow-on milk according to claim 1, wherein a combination of a compound having formula (1) and a compound having formula (2) is used, and the combination is present in a composition containing the compound having formula (1) in an amount of at least 10% by weight of the total triglycerides and the compound having formula (2) in an amount of at least 10% by weight of the total triglycerides.

3. An infant formula or follow-on milk according to claim 1 or 2, wherein a combination of a compound having formula (1), a compound having formula (2), a compound having formula (3), and a compound having formula (4) is used.

4. R １ 、 R ２ 、 R ３ 、 R ４ 、 R ５ 、 and / or R ６ is an acyl group of an unsaturated fatty acid, or R １ 、 R ２ 、 R ３ 、 R ４ 、 R ５ 、 and / or R ６ is an acyl group of a monounsaturated fatty acid, the infant formula or follow-on milk according to any one of claims 1 to 3.

5. R １ , R ２ , R ３ , R ４ , R ５ , and / or R ６ The infant formula or follow-on milk according to any one of claims 1 to 4, wherein the acyl group is a fatty acid selected from the group consisting of oleic acid, palmitic acid, or linoleic acid.

6. R １ , R ２ , R ３ , R ４ , R ５ , and R ６ Each of the members is an acyl group of oleic acid, according to any one of claims 1 to 5.

7. The infant formula or follow-on milk according to any one of claims 1 to 6, wherein the compound having formula (1) is the following compound. 【Chemistry 2】

8. The infant formula or follow-on milk according to any one of claims 1 to 6, wherein the compound having formula (2) is the following compound. 【Transformation 3】

9. The infant formula or follow-on milk according to any one of claims 1 to 6, wherein the compound having formula (3) is the following compound. 【Chemistry 4】

10. The infant formula or follow-on milk according to any one of claims 1 to 6, wherein the compound having formula (4) is the following compound. 【Transformation 5】

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