EP4228437A1 - Composition nutritionnelle - Google Patents
Composition nutritionnelleInfo
- Publication number
- EP4228437A1 EP4228437A1 EP21782446.5A EP21782446A EP4228437A1 EP 4228437 A1 EP4228437 A1 EP 4228437A1 EP 21782446 A EP21782446 A EP 21782446A EP 4228437 A1 EP4228437 A1 EP 4228437A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- nutritional composition
- calcium
- triglycerides
- milk
- protein
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 184
- 235000016709 nutrition Nutrition 0.000 title claims abstract description 111
- 239000011575 calcium Substances 0.000 claims abstract description 73
- BECPQYXYKAMYBN-UHFFFAOYSA-N casein, tech. Chemical compound NCCCCC(C(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(CC(C)C)N=C(O)C(CCC(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(C(C)O)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(COP(O)(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(N)CC1=CC=CC=C1 BECPQYXYKAMYBN-UHFFFAOYSA-N 0.000 claims abstract description 73
- 235000021240 caseins Nutrition 0.000 claims abstract description 73
- 239000005018 casein Substances 0.000 claims abstract description 65
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims abstract description 62
- 229910052791 calcium Inorganic materials 0.000 claims abstract description 62
- 150000003626 triacylglycerols Chemical class 0.000 claims abstract description 61
- 235000018102 proteins Nutrition 0.000 claims abstract description 54
- 102000004169 proteins and genes Human genes 0.000 claims abstract description 54
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 54
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 53
- 238000000034 method Methods 0.000 claims abstract description 51
- IPCSVZSSVZVIGE-UHFFFAOYSA-N palmitic acid group Chemical group C(CCCCCCCCCCCCCCC)(=O)O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 claims abstract description 32
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 26
- 239000000843 powder Substances 0.000 claims abstract description 19
- 150000001720 carbohydrates Chemical class 0.000 claims abstract description 14
- 235000014633 carbohydrates Nutrition 0.000 claims abstract description 14
- 238000002360 preparation method Methods 0.000 claims abstract description 12
- 206010010774 Constipation Diseases 0.000 claims abstract description 7
- 230000002265 prevention Effects 0.000 claims abstract description 4
- 108010046377 Whey Proteins Proteins 0.000 claims description 35
- 150000003839 salts Chemical class 0.000 claims description 32
- 102000007544 Whey Proteins Human genes 0.000 claims description 26
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- 235000021243 milk fat Nutrition 0.000 claims description 24
- 150000004665 fatty acids Chemical group 0.000 claims description 23
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- 210000004251 human milk Anatomy 0.000 claims description 21
- 241000283690 Bos taurus Species 0.000 claims description 18
- 235000014113 dietary fatty acids Nutrition 0.000 claims description 18
- 239000000194 fatty acid Substances 0.000 claims description 18
- 229930195729 fatty acid Natural products 0.000 claims description 18
- 159000000007 calcium salts Chemical class 0.000 claims description 16
- 229920001542 oligosaccharide Polymers 0.000 claims description 16
- 102000005701 Calcium-Binding Proteins Human genes 0.000 claims description 15
- 108010045403 Calcium-Binding Proteins Proteins 0.000 claims description 15
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- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 claims description 14
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- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 claims description 12
- 239000006071 cream Substances 0.000 claims description 11
- 239000001506 calcium phosphate Substances 0.000 claims description 10
- 229910000389 calcium phosphate Inorganic materials 0.000 claims description 10
- 235000008939 whole milk Nutrition 0.000 claims description 10
- 235000011010 calcium phosphates Nutrition 0.000 claims description 9
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 9
- 238000002156 mixing Methods 0.000 claims description 8
- 229910000019 calcium carbonate Inorganic materials 0.000 claims description 7
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- 239000008101 lactose Substances 0.000 claims description 5
- 239000001508 potassium citrate Substances 0.000 claims description 5
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- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 claims description 5
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical group CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 claims description 4
- SNFSYLYCDAVZGP-UHFFFAOYSA-N UNPD26986 Natural products OC1C(O)C(O)C(C)OC1OC1C(OC2C(OC(O)C(O)C2O)CO)OC(CO)C(O)C1O SNFSYLYCDAVZGP-UHFFFAOYSA-N 0.000 claims description 4
- QEEAPRPFLLJWCF-UHFFFAOYSA-K potassium citrate (anhydrous) Chemical compound [K+].[K+].[K+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O QEEAPRPFLLJWCF-UHFFFAOYSA-K 0.000 claims description 4
- 238000001694 spray drying Methods 0.000 claims description 4
- 229940062827 2'-fucosyllactose Drugs 0.000 claims description 2
- HWHQUWQCBPAQQH-UHFFFAOYSA-N 2-O-alpha-L-Fucosyl-lactose Natural products OC1C(O)C(O)C(C)OC1OC1C(O)C(O)C(CO)OC1OC(C(O)CO)C(O)C(O)C=O HWHQUWQCBPAQQH-UHFFFAOYSA-N 0.000 claims description 2
- 125000004432 carbon atom Chemical group C* 0.000 claims description 2
- HWHQUWQCBPAQQH-BWRPKUOHSA-N 2-fucosyllactose Chemical compound O[C@H]1[C@H](O)[C@H](O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@H]([C@H](O)CO)[C@H](O)[C@@H](O)C=O HWHQUWQCBPAQQH-BWRPKUOHSA-N 0.000 claims 1
- 125000005313 fatty acid group Chemical group 0.000 abstract 1
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- 229960005069 calcium Drugs 0.000 description 57
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- 235000002639 sodium chloride Nutrition 0.000 description 26
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- 239000003925 fat Substances 0.000 description 23
- 235000019197 fats Nutrition 0.000 description 23
- 239000004615 ingredient Substances 0.000 description 21
- 230000002496 gastric effect Effects 0.000 description 19
- 239000000047 product Substances 0.000 description 15
- 239000005862 Whey Substances 0.000 description 13
- 238000009472 formulation Methods 0.000 description 13
- 230000015572 biosynthetic process Effects 0.000 description 12
- 239000006228 supernatant Substances 0.000 description 12
- 238000000338 in vitro Methods 0.000 description 11
- 239000008188 pellet Substances 0.000 description 10
- 210000002784 stomach Anatomy 0.000 description 10
- 210000001035 gastrointestinal tract Anatomy 0.000 description 9
- PEDCQBHIVMGVHV-UHFFFAOYSA-N glycerol group Chemical group OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 9
- 239000007788 liquid Substances 0.000 description 9
- 239000002245 particle Substances 0.000 description 9
- 229960001714 calcium phosphate Drugs 0.000 description 8
- 229940021722 caseins Drugs 0.000 description 8
- 238000001095 inductively coupled plasma mass spectrometry Methods 0.000 description 8
- 235000020183 skimmed milk Nutrition 0.000 description 8
- 235000020209 toddler milk formula Nutrition 0.000 description 8
- 235000015112 vegetable and seed oil Nutrition 0.000 description 8
- 238000000502 dialysis Methods 0.000 description 7
- IPCSVZSSVZVIGE-UHFFFAOYSA-M hexadecanoate Chemical compound CCCCCCCCCCCCCCCC([O-])=O IPCSVZSSVZVIGE-UHFFFAOYSA-M 0.000 description 7
- 239000008158 vegetable oil Substances 0.000 description 7
- 235000001014 amino acid Nutrition 0.000 description 6
- 229940024606 amino acid Drugs 0.000 description 6
- 235000020218 follow-on milk formula Nutrition 0.000 description 6
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- 239000012528 membrane Substances 0.000 description 6
- 150000003904 phospholipids Chemical class 0.000 description 6
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- 102000014171 Milk Proteins Human genes 0.000 description 5
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- 230000015556 catabolic process Effects 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 235000021239 milk protein Nutrition 0.000 description 5
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical class OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 4
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- 102000057297 Pepsin A Human genes 0.000 description 4
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- FNAQSUUGMSOBHW-UHFFFAOYSA-H calcium citrate Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O.[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O FNAQSUUGMSOBHW-UHFFFAOYSA-H 0.000 description 4
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- SNFSYLYCDAVZGP-OLAZETNGSA-N 2'-fucosyllactose Chemical compound O[C@H]1[C@H](O)[C@H](O)[C@H](C)O[C@H]1O[C@H]1[C@H](O[C@@H]2[C@H](OC(O)[C@H](O)[C@H]2O)CO)O[C@H](CO)[C@H](O)[C@@H]1O SNFSYLYCDAVZGP-OLAZETNGSA-N 0.000 description 3
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- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
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- RFWLACFDYFIVMC-UHFFFAOYSA-D pentacalcium;[oxido(phosphonatooxy)phosphoryl] phosphate Chemical compound [Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O.[O-]P([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O RFWLACFDYFIVMC-UHFFFAOYSA-D 0.000 description 1
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Classifications
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/40—Complete food formulations for specific consumer groups or specific purposes, e.g. infant formula
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/125—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives containing carbohydrate syrups; containing sugars; containing sugar alcohols; containing starch hydrolysates
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/16—Inorganic salts, minerals or trace elements
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/17—Amino acids, peptides or proteins
- A23L33/19—Dairy proteins
Definitions
- the present invention relates to a nutritional composition, to a process for the preparation of such composition in powdered form and to particular uses of the nutritional composition.
- the protein systems of human milk and cows’ milk differ substantially, both quantitatively and qualitatively. Prominent quantitative differences include a lower total protein content, often expressed as the total nitrogen content multiplied by 6.25 or 6.38, of human milk (11 g/L) compared to cows’ milk (33-35 g/L).
- Total nitrogen containing components in milk can be divided into true protein nitrogen and non-protein nitrogen (NPN), with caseins and serum proteins (the latter also called whey proteins) as the main classes of proteins.
- caseins are the proteins from milk that precipitate at pH 4.6, whereas whey proteins remain soluble at this pH.
- the ratio of whey protein to casein is typically about 60:40 to 50:50, whereas the whey protein to casein ratio is approximately 18:82 in cows’ milk.
- infant formulas have become better and better over time, there are still important differences between human milk and cows’ milk based infant formulas that may lead to infants who are fed with such infant formula to suffer from gut discomfort and/or even constipation caused by a poorer gastric digestion. This may lead to babies crying more and hence to more anxiety with parents.
- breast-fed infants exhibit frequent and looser/watery stools which, in return, leads to a better gut comfort.
- Casein molecules are used in food industry as ingredients. Casein molecules can be used as isolated forms and under micellar form consisting in an association of different casein molecules and calcium phosphate (C. Broyard et al "Modifications of structures and functions of caseins: a scientific and technological challenge", Dairy Sciency & Technology, Institute National de la Recherche Agronomique, INRA, FR, vol. 95, no. 6, pages 831-862).
- US20 16/158287 relates to nutritional compositions for infants for example infant formulas. It describes an experimental formula comprising whey or milk protein concentrate solids rich in phospholipids and milk fat globule membrane (MFGM) for use in the prevention and prophylaxis of otitis, wherein the whey or milk protein concentrate solids rich in phospholipids and MFGM further comprises one or more bioactive compounds selected from the group consisting of lactoferrin, a-lactalbumin, butyrophilin, MUC1, PAS6/7 (lactadherin), gangliosides, CD 14, TLR1 and TLR4, IgG, cGMP, sialic acid, and phospholipids, and wherein said whey or milk protein concentrate solids rich in phospholipids and MFGM comprises at least 20 wt% phospholipids based on total lipid of the enriched phospholipid whey or milk protein concentrate solid source.
- US2016/158287 does not disclose the form of the casein
- US 2014/249103 discloses nutritional compositions including human milk oligosaccharides that can be administered to individuals including preterm infants, infants, toddlers, and children for improving gastrointestinal function and tolerance, as well as the growth of beneficial bacteria; it further discloses suitable methods of using the nutritional compositions including the human milk oligosaccharides.
- An important cause for gut discomfort when using infant formula is the formation of curd in the stomach during gastric digestion. Such curd is formed by casein micelles clogging together. If too much of such solid curd is formed, emptying of the stomach becomes more difficult and a feeling of gut discomfort or even constipation may be the result.
- the present invention aims to provide a nutritional composition which exhibits improved gastric digestion properties by avoiding, or anyhow significantly reducing, curd formation in the stomach during the gastric digestion process, thereby facilitating stomach emptying and improving gut comfort.
- the present invention relates to a synthetic nutritional composition wherein the protein component comprises casein micelles having a protein-bound calcium content of 7.5 mmoles or less per 10 grams of casein and total calcium content is at least 3.5 g/kg with the ratio of non-protein nitrogen (NPN) to total nitrogen (TN) being 0.7 or less and wherein the fat composition comprises triglycerides and the triglycerides comprise palmitic acid residues which make up more than 10% (w/w) of all fatty acid residues present in the triglycerides; and at least 10 % of the palmitic acid residues in the triglycerides being in the Sn2 position of the triglycerides.
- NPN non-protein nitrogen
- TN total nitrogen
- the invention further relates to a process for the preparation of such nutritional composition in powdered form, wherein at certain moments during the preparation salts (sometimes also referred to as minerals) are added which comprise (i) a calcium-binding acid or water-soluble salt thereof and (ii) at least one calcium salt selected from calcium citrate, calcium phosphate and calcium carbonate.
- salts sometimes also referred to as minerals
- at certain moments during the preparation salts are added which comprise (i) a calcium-binding acid or water-soluble salt thereof and (ii) at least one calcium salt selected from calcium citrate, calcium phosphate and calcium carbonate.
- the present invention relates to a synthetic nutritional composition
- a synthetic nutritional composition comprising carbohydrates, protein and a fat composition, wherein:
- the nutritional composition has a total calcium content on dry matter of at least 3.5 g/kg;
- the protein comprises casein
- the nutritional composition has a content of protein-bound calcium of 7.5 mmoles or less, preferably between 3 and 6 mmoles, per 10 grams of casein;
- the ratio NPN to TN is 0.7 or less, preferably between 0.01 and 0.5, more preferably between 0.03 and 0.3, most preferably between 0.05 and 0.15, with:
- NPN non-protein nitrogen in the nutritional composition in grams per 100 grams of nutritional composition (g/100 g);
- TN total nitrogen
- the fat composition comprises triglycerides and the triglycerides comprise palmitic acid residues which make up more than 10% (w/w) of all fatty acid residues present in the triglycerides;
- synthetic means obtained by chemical and/or biological means, to the contrary of “natural (found in the nature)”, for example a synthetic nutritional composition is not of human or animal origin (e.g. it is not breast milk or cow’s milk).
- An infant formula is an example of a synthetic nutritional composition; it aims to replicate the nutritional value of human milk which is not a simple task.
- the term “nutritional” means that it nourishes a subject.
- the synthetic nutritional compositions according to the invention are typically to be taken by enteral, oral, orogastric or nasogastric feeding, preferably orally, and may include a carbohydrate, fat and a protein source.
- the synthetic nutritional compositions according to the invention may be intended for infants and/or young children, and may be for example be formulated as an infant formula, a growing-up milk, or any other milk-based nutritional composition, a supplement (or a complement), or as a fortifier such as a milk fortifier (e.g. human milk fortifier).
- the nutritional compositions can be in powder or liquid form.
- the effect of the specified levels of protein-bound calcium may be increased by using higher proportion of palmitate at the Sn2 position of triacylglycerols, as it is known that this improves dietary fat and calcium absorption compared to a diet with a lower Sn2 palmitate level (e.g. infant formula with only vegetable oil), see e.g. WO2013068879.
- Sn2 palmitate levels is known to reduce gut inflammation, stool fat, constipation, palmitic acid soaps and reduces crying. As such it leads to increased gut comfort.
- Sn2 also referred to as Sn-2, sn2, or sn-2
- Sn-2 also referred to as Sn-2, sn2, or sn-2
- Sn-2 Palmitate structured triglycerides also referred to as structured lipids
- Enzymatic processes on vegetable oils enables changing the position of palmitic acid to the Sn-2 position, such products are commercially available e.g. Betapol ® 45 from Bunge Loders Croklaan.
- the desired level of Sn2 palmitate i.e. % of the palmitic acid residues in the triglycerides being in the Sn2 position, may be obtained by varying the ratio between milk fat, vegetable oils, and structured lipids.
- the wt% of palmitic acid with respect to all fatty acid residues in triglycerides can be varied.
- the fatty acid composition from various vegetable oils may for example be found from various sources such as Wikipedia or from E.G. Giakoumis (E. G. Giakoumis, Renewable Energy 126 (2016) pp 403- 419, Table 1).
- Calcium is an important element that needs to be present in the nutritional composition. Minimum levels are prescribed by the relevant regulations. Calcium could come from various sources, such as from any milk-based ingredient, notably skimmed milk, whole milk and/or cream, or from one or more calcium salts that are added separately. For the purpose of the present invention it is important that the total calcium content on dry matter in the nutritional composition is at least 3.5 grams of Ca per kilogram (g/kg). Preferably, total calcium content is in the range from 3.5 to 9.5, more preferably 3.6 to 8.0 g/kg on dry matter.
- ICP-MS Inductively Coupled Plasma Mass Spectrometry
- the calcium in the nutritional composition can essentially come from two sources. Firstly, calcium could come from the dairy ingredients used as starting materials for the nutritional composition. Such dairy ingredients could, for example, include cream, skimmed milk, whole milk and/or a whey ingredient such as native whey, demineralized whey or a combination of both. Secondly, calcium could also originate from calcium salts that are added. Such calcium salts should be salts that are allowable for use in food products and in particular in nutritional compositions for infants and young children. Examples of suitable calcium salts are calcium citrate, calcium phosphate and calcium carbonate. Using a combination of two or more of such calcium sources is also possible. As will be appreciated by those skilled in the art calcium phosphate salts can appear in different forms.
- the calcium phosphate salt can be in various forms, provided that in each case one mole of the salt contains at least one mole of calcium and one mole of orthophosphate.
- Suitable examples include calcium hydrogen phosphate, calcium dihydrogen phosphate, calcium phosphate, dicalcium disphosphate, calcium triphosphate and tricalcium phosphate.
- the nutritional composition of the present invention comprises a protein component. It was found to be critical that the calcium bound to the proteins present is carefully controlled and should not exceed a certain value in order to minimize or even completely avoid curd formation in the stomach.
- cows’ milk proteins can be divided into caseins and serum proteins (also called whey proteins). The ratio of whey protein to casein in cows’ milk is approximately 18:82. Under neutral conditions the vast majority of caseins will be present as micelles.
- the calcium can be present as (dissolved) salt and as protein-bound calcium. The majority of the protein-bound calcium (more than 90 wt%, typically more than 95 wt%) will be bound into the caseins and casein micelles with the remainder up to 100% being associated with whey proteins.
- the content of such protein-bound calcium should be 7.5 mmoles or less, preferably between 3 and 6 mmoles, per 10 grams of casein.
- the amount of protein-bound calcium in a nutritional composition is determined as follows. Referring to Figure 1 for a schematic representation of the procedure, the liquid nutritional composition NC (if in powder form, the nutritional composition is first reconstituted in water) is first equilibrated at 20 °C for 1 hour and centrifuged at 200 x g for 15 minutes at 20 °C to remove insoluble calcium salts, followed by separation of the pellet (PEL1) and supernatant (SUP). The SUP is subsequently equilibrated at 20°C for 2 hours prior to centrifugation at 100,000 x g for 60 minutes at 20°C.
- the resulting liquid serum layer (SER) is separated from the cream layer (CRE) and pellet (PEL2) and subsequently filtered through a 10 kDa membrane to obtain the 10 kDa-permeable fraction of the sample (permeate, PERlOkD).
- Total calcium ( ⁇ Ca>) concentration in grams per kilogram (g/kg) in the SUP and the PERlOkD is determined by the ICP-MS method described above.
- concentration of protein-bound calcium (PBCa, in g/kg) is then determined as the fraction of calcium in milk that does not permeate through the 10 kDa membrane:
- Casein nitrogen content (CN) in a milk based liquid is determined as described in ISO17997/IDF 29-1 - Determination of casein nitrogen content - Part 1 - Indirect method (Reference method). Casein content in the milkbased liquid (Cas) in g/100 g then is:
- Casein content (Cas) in nutritional compositions can also be determined differently, particularly if the processing history of the composition is unknown and whey protein denaturation may have occurred during such processing. In such a case, some of the whey protein will be determined as CN in aforesaid method ISO17997/IDF 29-1 and, as a result, inaccurate values for CN will arise and the resulting casein content will not be correct. When using the more elaborate method described below, however, one would always find the correct casein content.
- TN total nitrogen content
- NPN non-protein nitrogen
- amino acid composition of the composition are determined first.
- TN is determined using the Kjeldahl method as described in method ISO 8968-1 I IDF 020-1 (Milk and milk products - Determination of Nitrogen Content - Part 1: Kjeldahl Principle and Crude Protein Calculation).
- NPN is determined as described in method ISO 8968-4 I IDF 020-4 (Milk and milk products - Determination of Nitrogen Content - Part 4: Determination of non-protein-nitrogen content). Both TN and NPN are expressed in grams per 100 grams of nutritional composition (g/100 g).
- Amino acid composition is determined by ion exchange chromatography based on methods described in AO AC Official Method 994.12 - Amino Acids in Feeds. From the concentrations of the amino acids proline (Pro), phenylalanine (Phe), aspartic acid plus asparagine (Asp + Asn) and alanine (Ala) the ratio of whey proteins to casein in the nutritional composition is subsequently calculated as described in AO AC Official Method 2012.7 - Calculation of Whey Protein Fraction in Milk-Based Infant Formula. Based on TN and NPN total protein content can be calculated as (TN-NPN)*6.38. Based on total protein content and the ratio of whey proteins to casein, casein content in the nutritional composition (in g/100 g) can subsequently be determined.
- the amount of protein-bound calcium (i.e. the ratio PBCa/Cas) is then calculated as amount of protein-bound calcium in mmoles per 10 grams of casein by using the formula:
- Cas with MW(Ca) being the mole weight of calcium in g/mole ( 40 g/mole), PBCa being the protein-bound calcium in g/kg and Cas being the amount of casein in g/100 g (which is equivalent to an amount *10g/kg).
- the amount of protein-bound calcium is determined at standard pH of about 7 (i.e between 6.5 and 7.5). In order to ensure that the amount of protein-bound calcium is below the 7.5 mmoles/10 g casein-threshold, specific measures in the preparation of the nutritional composition may be needed. However, it could also be that certain cow breeds produce milk having a protein-bound calcium content in the desired range.
- calcium-binding acids or water-soluble salts thereof that can be used in food products can be used.
- Suitable examples are citric acid and citrate salts. Since potassium and sodium are usually also added as salts, the use potassium and/or sodium citrate as calcium binding substances is preferred.
- the amount of calcium-binding substance(s) to be used will depend on the proteinbound calcium level in the milk which is used as the starting material.
- measures to bring the protein-bound calcium to the right level could also involve adding caseinates as low calcium casein source or processing of the starting milk to reduce the amount of protein-bound calcium.
- processing could involve membrane filtration under specific conditions, treating the starting milk with an ion exchange resin and/or subjecting the milk to a electrodialysis treatment.
- the ratio of NPN to TN in the nutritional composition should be 0.7 or less and preferably ranges between 0.01 and 0.5, more preferably between 0.03 and 0.3 and most preferably between 0.05 and 0.15.
- a high ratio of NPN/TN in nutritional compositions i.e. above 0.7 is indicative of the use of extensively hydrolyzed proteins in these products.
- a key aspect of the present invention is that a large proportion of the proteins present in the nutritional composition have their native form and hence are in a non-hydrolyzed state.
- Total nitrogen, TN is determined using the Kjeldahl method as described in method ISO 8968-1 I IDF 020-1 (Milk and milk products - Determination of Nitrogen Content - Part 1: Kjeldahl Principle and Crude Protein Calculation).
- non-protein nitrogen content, NPN for the reconstituted samples is determined as described in method ISO 8968-4 I IDF 020-4 (Milk and milk products - Determination of Nitrogen Content - Part 4: Determination of non- protein-nitrogen content). Both TN and NPN are expressed in grams per 100 grams of nutritional composition (g/100 g).
- the nutritional composition of the invention has a content of protein-bound calcium of between 3 and 7 mmole per 10 grams of casein, preferably between 4 and 7 mmole per 10 grams of casein, more preferably between 4 and 6.5 mmole per 10 grams of casein, most preferably between 4 and 6 mmole per 10 grams of casein.
- the triglycerides in the nutritional composition of the invention comprise palmitic acid residues which make up more than 15% (w/w) of all fatty acid residues present in the triglycerides, preferably more than 20%.
- the nutritional composition of the invention comprises at least 15 % of the palmitic acid residues in the triglycerides in the Sn2 position of the triglycerides, preferably at least 20%, 25%, 30%, or even, at least 35% of the palmitic acid residues in the triglycerides being in the Sn2 position.
- the triglycerides in the nutritional composition of the invention comprise palmitic acid residues which make up more than 15% (w/w) of all fatty acid residues present in the triglycerides and at least 15 % of the palmitic acid residues in the triglycerides being in the Sn2 position of the triglycerides, preferably at least 20%, 25%, 30%, or even at least 35% of the palmitic acid residues in the triglycerides being in the Sn2 position.
- the triglycerides in the nutritional composition of the invention comprise palmitic acid residues which make up more than 25% (w/w) of all fatty acid residues present in the triglycerides and at least 15 % of the palmitic acid residues in the triglycerides being in the Sn2 position of the triglycerides, preferably at least 20%, 25%, 30%, or even at least 35% of the palmitic acid residues in the triglycerides being in the Sn2 position.
- the fat composition used in the nutritional composition could in principle be any fat composition known for use in infant formula and formula for young children. Such fat composition could consist of two or more components added at different stages in the preparation process. It is, however, preferred that at least part of the total fat composition used originates from bovine milk fat. More specifically, it is preferred that the fat composition comprises at least 20% by weight, preferably at least 45% by weight, based on total weight of the fat composition of triacylglycerols (TAG) originating from a bovine milk fat source.
- TAG triacylglycerols
- Preferred bovine milk fat sources are whole milk, cream and anhydrous milk fat. Any one of these bovine milk fat sources could be used as well as any combination of two or more of these bovine milk fat sources.
- the content of the different fatty acids in the fat composition can be determined by standard method ISO 15884/IDF 182:2002 (Milk fat - Preparation, of fatty acid methyl esters) and ISO 15885/IDF 184 (Milk fat - Determination of the fatty acid composition by gas-liquid chromatography).
- the distribution of fatty acids over the glycerol backbone can be determined according to the method disclosed in Luddy,F.E., Barford, R.A., Herb,S.F., Magidman,P. and Riemenschneider,R.W. J. Am. Oil Chem. Soc., 41, 693-696 (1964).
- this method involves hydrolysis of TAG by a sn-1,3 specific pancreatic lipase (porcine).
- the required 2 -monoacylglycerols formed are isolated by thin layer chromatography and these are subsequently methylated for gas chromatographic analysis and quantified in molar concentrations.
- the molar concentration of a fatty acid at the sn-1,3 positions of the glycerol backbone [FA(sn-l,3)] is calculated from the molar concentration of this fatty acid in the total fat [FA- TAG] and the molar concentration of this fatty acid at the sn-2 position [FA(sn-2)] via the formula:
- the nutritional composition of the invention also comprises carbohydrates.
- carbohydrates will largely consist of lactose.
- Other carbohydrate ingredients such as oligosaccharides (for example, fructo-oligosaccharides and/or galacto-oligosaccharides), may be included as well.
- the carbohydrates include non-digestible oligosaccharides such as galacto-oligosaccharides, fructooligosaccharides, inulin, xylo-oligosaccharides, which are all readily commercially available.
- the non-digestible oligosaccharides include galacto-oligosaccharides and fructo-oligosaccharides.
- the composition of the invention comprises between 0.1 and 10 gram of non-digestible oligosaccharides per 100 gram of composition, preferably between 1.0 and 6.0 gram, more preferably it comprises between 0.1 and 10 gram of galactooligosaccharides per 100 gram of composition, preferably between 1.0 and 6.0 gram of galacto-oligosaccharides.
- the composition of the invention comprises between 1 and 30 gram of non-digestible oligosaccharides per 100 gram of composition, preferably between 2.0 and 25 gram, more preferably it comprises between 5 and 20 gram of galacto-oligosaccharides per 100 gram of composition, preferably between 10 and 20 gram of galacto-oligosaccharides.
- Galacto-oligosaccharides are for example offered for sale by FrieslandCampina (NL).
- the nutritional composition of the invention also comprises at least one human milk oligosaccharide.
- Suitable human milk oligosaccharides include fucosylated lactoses, in particular 2’-fucosyllactose (2’-FL) and 3-fucosyllactose (3-FL), lacto-N-tetraose (LNT), lacto-N-neotetraose (LNnT) and 6’-siallyllactose (6’-SL). Of these, 2’-FL is most preferred.
- the total amount of human milk oligosaccharide on dry matter in the nutritional composition is suitably 0.05 to 2.0 grams, more suitably 0.1 to 1.0 grams, per 100 grams (g/100 g).
- the nutritional composition is particularly suitable for human subjects of 0 to 36 months of age, in particular infants (a person of 0-12 months of age according to the CODEX Alimentarius (CODEX STAN 72-1981), further referred to as the CODEX) and young children up to the age of 36 months.
- Nutritional compositions for infants are commonly referred to as infant formula, for older children the terms follow on formula and growing up milk, as described hereinbefore, are also commonly used.
- the nutritional composition according to the present invention should contain the ingredients in the amounts as prescribed by the CODEX and, if needed, as prescribed by additional regulations of individual countries.
- the nutritional composition according to the invention for infants comprises the protein, carbohydrates and fat composition as described above, and will also comprise vitamins, salts and trace elements and the other substances in accordance with the specifications prescribed by the CODEX and, if needed, by additional national regulations.
- the nutritional composition of the invention can be in the form of ready-to- feed formulation, either in drinkable or spoonable form, or in the form of a powdered formula. In the form as produced, transported and sold, it is suitably in powder form. The powder can subsequently be mixed with water to obtain the ready-to-drink or ready-to-spoon formula as consumed by the infant or young child.
- the pH of the final nutritional composition in its ready-to-drink or ready-to-spoon form would typically be between 6.5 and 7.5, which is the standard pH for this type of food product.
- the present invention also relates to a process for the preparation of a nutritional composition in powder form as described above, which process comprises the steps of
- step (b) spray drying the mixture resulting from step (a) into a powder
- step (c) optionally dry-blending salts into the powder resulting from step (b) to obtain the nutritional composition, wherein the salts comprise
- step (ii) at least one calcium salt selected from calcium phosphate and calcium carbonate, and wherein the calcium-binding acid or water-soluble salt thereof is added in step (a) and the at least one calcium salt is added in step (a) and/or in step (c).
- Step (a) of the process can be carried out by any way known in the art.
- Each of the components of the mixture i.e. the whey protein source, the casein source, the fat source, the carbohydrate source and the salts, may itself consist of two or more sub-components or may be combined with one or more of the other components into a single ingredient.
- the fat source could consist of one or more bovine milk fat components and one or more vegetable fats and/or oils components, each of which could be added at different stages during step (a).
- whole milk would be used as fat source, whey protein source, casein source, carbohydrate source and source of salts, all combined in a single ingredient.
- skimmed milk would be a combined whey protein source, casein source, carbohydrate source and source of salts.
- the salts could also comprise multiple different salt components, which could be added during step (a), but possibly also during dry-blending step (c).
- the salts should anyhow comprise
- calcium citrate, calcium phosphate and calcium carbonate being preferred.
- the calcium-binding acid or water-soluble salt thereof is suitably selected from citric acid, sodium citrate, potassium citrate and any combination of two or more of these, preferably a combination of sodium citrate and potassium citrate.
- the whey protein source used could in principle be any whey protein source conventionally used or useful in the preparation of nutritional compositions.
- demineralized whey is suitably used.
- a whey product isolated from raw milk with a minimum of heat treatments to retain as much of the whey proteins in their native state could also be used.
- step (a) could be carried out by the successive steps of:
- the resulting homogenized mixture can subsequently be spray dried in step (b).
- the casein source and milk fat source used in step (al) could be two distinct components, such as skimmed milk (casein source) and cream or anhydrous milk fat (milk fat source), but could also be combined into as single component, such as whole milk.
- step (a) As is well known evaporation, pasteurization and homogenization, if needed, can be carried out at different moments in different orders during step (a).
- the example given above is just one way of blending all ingredients together. In principle, any order of steps resulting in a uniform mixture of all ingredients could be used.
- step (b) the mixture resulting from step (a) is spray-dried to obtain the nutritional composition in powder form.
- Spray-drying is a well-known technique and any spray drying technique suitable for producing a powder from the liquid nutritional composition mixture resulting from step (a) could be used.
- step (c) further ingredients can be dry-blended into the powder resulting from step (b) to obtain the final nutritional composition powder.
- One ingredient that could be dry -blended in this step (c) is (part of) the salts, in particular calcium citrate, calcium phosphate and/or calcium carbonate.
- the calcium-binding acid or water-soluble salt thereof is added in step (a) whilst the calcium salt(s) is(are) added in step (a) and/or in step (c).
- the calcium-binding component is suitably added before the addition of the calcium salt(s).
- other ingredients could also be added during dry-blending step (c).
- Such ingredients include, for example, vitamins, lactose, galacto-oligosaccharides (GOS), human milk oligosaccharides (HMOs) and (premixes of) trace elements that are suitably present in nutritional compositions. This is well known in the art.
- the nutritional composition of the invention was found to lead to less curd formation in the stomach -or even no curd formation at all-, thereby facilitating stomach emptying and gastric digestion. This helps to prevent gut discomfort and constipation in infants and little children. Accordingly, in a further aspect the present invention relates to the nutritional composition as described above for use in the prevention of gut discomfort and constipation in human subjects, suitably human subjects of 0 to 36 months of age.
- Figure 1 is a schematic representation of the procedure for determining protein -bound calcium.
- Figure 2 shows the set-up of the in vitro gastric digestion model used.
- Figure 3 shows photographic images after in-vitro gastric digestion of two samples according to the invention and one comparative sample at different pH values.
- Figure 4 shows SDS-PAGE electrophoretograms of the model formulations tested.
- Figure 5 shows photographic images after in-vitro gastric digestion of a nutritional composition according to the invention.
- Figure 6 shows SDS-PAGE electrophoretograms of the nutritional composition of Example 3.
- Example 2 For this purpose, a batch of 50 kg of pasteurized skim milk was obtained. Three subsamples (200 g each) were taken, one of which (Sample 2) was kept at its original pH, whereas Sample 1 was adjusted to pH 5.7 by the addition of 1 M hydrochloric acid (acid) and Sample 3 was adjusted to pH 8.0 by the addition of 1 M sodium hydroxide (base). The pH adjustment was carried out at 5°C, with milk samples as well as acid and base equilibrated at this temperature for 1 hour prior to pH adjustment.
- the dialysis tubes were transferred to another container containing 5000 g of the original pasteurized skim milk at 5°C and dialysis was again conducted under the same conditions for 24 h. Following this dialysis step, samples were removed from the dialysis tubing.
- the pH of the dialyzed Samples 1DIA (dialyzed sample obtained from Sample 1), 2DIA (dialyzed sample obtained from Sample 2) and 3DIA (dialyzed sample obtained from Sample 3) was 6.8 as measured at 20 °C using standard equipment.
- Samples 1DIA, 2DIA and 3DIA were subsequently used to prepare Model Formulations MFI, MF2 and MF3, respectively, by mixing 21 g of the respective dialyzed sample with 21 g of demineralized whey (DEMINAL® 90 Liquid ex FrieslandCampina Ingredients, having total protein content on dry matter of 13.5 wt%, lactose content on dry matter of 84.5 wt%, calcium content on dry matter of 0.040 wt% and total solids content of 28 wt%) and 58 g of milk permeate produced by ultrafiltration of pasteurized skimmed milk at 50°C using a 10 kDa membrane and having TN of less than 0.05 g/100 g, a lactose content of 4.9 wt%, and calcium content 0.028 wt%.
- demineralized whey DEMINAL® 90 Liquid ex FrieslandCampina Ingredients, having total protein content on dry matter of 13.5 wt%, lactos
- TN total nitrogen content
- NPN non-protein nitrogen content
- CN casein nitrogen content
- Ca calcium content
- PBCa/Cas protein-bound calcium to casein
- NPN was determined as described in method ISO 8968-4 / IDF 020-4 (Milk and milk products - Determination of Nitrogen Content - Part 4: Determination of non-protein-nitrogen content).
- CN was determined as described in ISO17997/IDF 29-1 - Determination of casein nitrogen content - Part 1 - Indirect method (Reference method). Casein content of the dialyzed sample is then calculated as CN*6.38.
- ICP-MS Inductively Coupled Plasma Atomic Mass Spectrometry
- ISO 21424 I IDF 243:2018 Milk, milk products, infant formula and adult nutritionals - Determination of minerals and trace elements - Inductively coupled plasma atomic mass spectrometry (ICP-MS) method .
- PBCa was determined as described hereinbefore with reference to Figure 1. Accordingly, samples of MFI, MF2 and MF3 were first equilibrated at 20 °C for 1 hour and centrifuged at 200 x g for 15 minutes at 20 °C to remove any insoluble calcium salts, followed by separation of the pellet and supernatant (SUP). The SUP is subsequently equilibrated at 20°C for 2 hours prior to centrifugation at 100,000 x g for 60 minutes at 20°C. The resulting liquid serum layer is separated from the cream layer and pellet and subsequently filtered through a 10 kDa membrane to obtain the 10 kDa-permeable fraction of the sample (PERlOkD). Total calcium ( ⁇ Ca>) concentration in grams per kilogram (g/kg) in the SUP and the PERlOkD was determined by the ICP-MS method described above. The concentration of protein-bound calcium (PBCa, in g/kg) was calculated as:
- the content of the different fatty acids in the lipid composition of the composition of the invention was be determined by standard method ISO 15884/IDF 182:2002 (Milk fat - Preparation of fatty acid methyl esters) and ISO 15885/IDF 184 (Milk fat - Determination of the fatty acid composition by gas-liquid chromatography). These ISO methods allow for determination of molar concentration of a fatty acid relative to total moles of this fatty acid in TAG ([FA- TAG]).
- the distribution of fatty acids over the glycerol backbone can be determined according to the method disclosed in Luddy,F.E., Barford, R.A., Herb,S.F., Magidman,P. and Riemenschneider,R.W.
- the milk fat source can in principle be any available bovine milk fat source, such as whole milk, cream, anhydrous milk fat (AMF) or milk fat fractions resulting from dry fractionation, critical CO2 extraction or other fractionation methods known in the art. It was, however, found particularly suitable to use whole milk and/or cream as the milk fat source.
- AMF anhydrous milk fat
- the amount of palmitic acid residues in the fat composition (also referred to as fat fraction) of MFI, MF2 and MF was 32 wt% of total fatty acid residues and 43% of the palmitic acid residues in the triglycerides was linked to the Sn2 position of the triglycerides.
- buffering curves of samples were first determined. For this purpose, samples were mixed with different volumes of 30 mM HC1 and the pH was determined. Based on the amount of 30 mM HC1 required to reach a certain pH and the pumping speed, the time point at which the sample should be taken could be calculated.
- a pepstatin A stock solution (0.02 g Pepstatin A in 18 mL methanol + 2 mL glacial acetic acid) was added at a level of 50 pL/10 mL of digested sample.
- Figure 3 shows photographic images of the model formulations after the in- vitro gastric digestion at different pH values. Diameter of the container in which the samples were photographed was 88 mm. Figure 3 shows that visible curd formation was not observed in Sample MFI (according to the invention) at any pH. In Sample MF2 (according to the invention), visible coagulation was not observed at pH 6.0, but as digestion progressed coagulation was observed at pH 5.0. Upon further progression, however no residual curd particles were observed in this sample, indicating the breakdown of curd particles formed initially. For Sample MF3 (comparative), strong coagulation was already observed at pH 6.0 and although some breakdown of particles was observed over time, even at the end of digestion (pH 3.5; >120 min) large residual curd particles were still observed.
- the samples MFI, MF2 and MF3 were also centrifuged, yielding a pellet and a supernatant (serum), and analyzed by SDS-PAGE under reducing conditions. As outlined in Figure 4, intact caseins, observed on SDS-PAGE gels in the range 25- 35 kDa, were only observed in the original samples and in the pellets formed.
- a composite blend was prepared from thermised whole milk, cream and demineralized whey. To that effect 145 kg of the whole milk was blended with 163 kg of the demineralized whey and 16 kg of the cream.
- TN, NPN, total calcium content and casein content of each ingredient and of the composite blend were determined as described above.
- protein-bound calcium (PBCa) of the milk and the composite blend was determined as described above.
- Fat content was determined using the Rose Gottlieb method (ISO 1211/IDF 1, Milk - Determination of fat content - Gravimetric method (Reference method). The results are indicated in Table 3. Table 3 Properties
- the composite blend was subjected to an evaporation treatment and further ingredients were added (see Table 4 for recipe).
- the resulting mixture was pasteurized, homogenized and spray-dried, yielding a spray-dried base powder with a moisture content of 2.5%.
- further ingredients were added by dry blending, which are shown in Table 4.
- the final nutritional composition powder had a moisture content of ⁇ 3.0%.
- Table 4 Nutritional composition recipe The powdered nutritional composition was reconstituted in demineralized water at 40°C for 60 min at a level of 13 g powder per 90 g of water. The level of casein mineralization (i.e. protein-bound calcium, PBCa/Cas) in the product was determined using the methods described above. The nutritional composition was analyzed using the methods described hereinbefore. Casein content was determined via TN, NPN and amino acid composition as described hereinbefore. Results are indicated in Table 5.
- casein mineralization i.e. protein-bound calcium, PBCa/Cas
- Example 4 Formulation of Infant formula and Growing up Milk
- Table 6 Infant formula and Growing- up Formula composition It is understood that the recipe for the infant formulation may likewise be used for a Follow-on-Formula.
- the infant formula or Follow-on-Formula may be powdered using techniques known in the art.
- the invention relates to a composition as specified in Table 6.
- the invention relates to a composition as specified in Table 6 wherein the galacto-oligosaccharides have been replaced with one or more other non-digestible oligosaccharides such as fructo-oligosaccharides, inulin or xylooligosaccharides.
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Abstract
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EP1062873A1 (fr) * | 1999-12-13 | 2000-12-27 | N.V. Nutricia | Aliment amélioré pour bébés, hydrolysat de protéines utilisables dans un tel aliment pour bébés, et procédé de préparation de cet hydrolysat |
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MY167583A (en) | 2011-11-10 | 2018-09-20 | Nestec Sa | Infant formula with high sn-2 palmitate and oligofructose |
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US20160015068A1 (en) * | 2014-07-16 | 2016-01-21 | Mead Johnson Nutrition Company | Nutritional formulas containing oil blends and uses thereof |
WO2016097220A1 (fr) * | 2014-12-19 | 2016-06-23 | Nestec S.A. | Nutrition de nourrisson avec des protéines hydrolysées, du calcium ionique et de l'acide palmitique |
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