Nutritional composition, method for producing the nutritional composition, and method for evaluating the bioavailability of copper in the nutritional composition

Abstract

To heighten bioavailability of copper in a nutritive composition.SOLUTION: The present technology relates to a nutritive composition containing a protein component and copper, wherein the nutritive composition contains lysinoalanine in a content of 3,000 μg or less per 1 g of the protein component, and the copper is contained in a content of 0.01 mg or more per 100 g of the nutritive composition. The nutritive composition may contain the protein component in a content of 1 g or more per 100 g of the nutritive composition. The protein component may comprise one or more of milk protein, collagen, soy protein, milk protein hydrolyzate, collagen hydrolyzate, and soy protein hydrolyzate. The present technology also provides a method of manufacturing the nutritive composition and a method of assessing the bioavailability of copper.SELECTED DRAWING: None

Description

Technical Field

[0001] The present technology relates to a nutritional composition, a method for producing the same, and a method for evaluating the same, and particularly relates to a nutritional composition containing a protein component and copper, a method for producing the same, and a method for evaluating the same.

Background Art

[0002] For nutritional supplementation, a nutritional composition such as a liquid diet may be used. Nutritional compositions contain various nutritional components depending on their purpose and use. One of the nutritional components is copper, which is known as a nutrient that helps in the formation of red blood cells. Copper also has various other roles. For example, copper is present at the active center of about 10 types of enzymes and is involved in energy production, iron metabolism, maturation of the extracellular matrix, production of neurotransmitters, and removal of reactive oxygen species. Also, a deficiency of copper can lead to copper deficiency.

[0003] Several techniques have been proposed so far to enhance the absorbability of trace elements such as copper. For example, Patent Document 1 below discloses "a nutritional composition characterized by containing soy milk and milk protein containing undigested casein as a main protein source." (Claim 1). It is described in the same document that "by containing soy milk and milk protein containing undigested casein in the nutritional composition, it is possible to supplement copper and zinc in the form of natural trace elements and has excellent absorption of trace elements into the living body." (Paragraph 0011).

Prior Art Documents

Patent Documents

[0004]

Patent Document 1

Summary of the Invention

Problems to be Solved by the Invention

[0005] If the bioavailability of copper contained in a nutritional composition can be improved, the value of that nutritional composition can be increased. Furthermore, a nutritional composition with improved copper bioavailability would be useful, for example, for people who are concerned about copper deficiency.

[0006] Based on the above, this technology aims to improve the bioavailability of copper contained in nutritional compositions. [Means for solving the problem]

[0007] The inventors have discovered that the bioavailability of copper can be improved by a specific nutritional composition.

[0008] In other words, this technology provides the following: [1] A nutritional composition containing protein components and copper, The nutritional composition, The protein component contains lysinoalanine in an amount of 3,000 μg or less per gram, The aforementioned copper is contained in an amount of 0.01 mg or more per 100 g of the nutritional composition. The aforementioned nutritional composition. [2] The nutritional composition according to [1], wherein the protein component is present in an amount of 1 g or more per 100 g of the nutritional composition. [3] The nutritional composition according to [1] or [2], wherein the protein component comprises one or more of milk protein, collagen, soy protein, milk protein hydrolysate, collagen hydrolysate, and soy protein hydrolysate. [4] The nutritional composition according to any one of [1] to [3], wherein the protein component comprises casein. [5] The nutritional composition according to any one of [1] to [3], wherein the protein component comprises micellar casein. [6] The nutritional composition according to [5], wherein the micelle casein is present in an amount of 1 g or more per 100 g of the nutritional composition. [7] The nutritional composition according to any one of [1] to [3], wherein the protein component comprises a casein hydrolysate or a collagen hydrolysate. [8] A method for producing a nutritional composition containing protein components and copper, The nutritional composition, The protein component contains lysinoalanine in an amount of 3,000 μg or less per gram, The aforementioned copper is contained in an amount of 0.01 mg or more per 100 g of the nutritional composition. The aforementioned manufacturing method. [9] The above manufacturing method is A preparation step of preparing a mixture containing the protein component and the copper, A sterilization step for sterilizing the mixture, The manufacturing method described in [8], including the method described in [8].

[10] The sterilization step is carried out such that the time for which the mixture is maintained at 100°C or above is 3 minutes or less, as described in [9].

[11] The manufacturing method according to [9] or

[10] , wherein the pH of the mixture is 6.5 or less.

[12] A method for evaluating the bioavailability of copper in a nutritional composition, A digestion process in which a nutritional composition containing protein components and copper is subjected to digestion using digestive enzymes to obtain digestive fluid. A separation step of separating the digestate so that at least two phases are formed, including an aqueous liquid phase, and Evaluation step for evaluating the bioavailability of copper in the nutritional composition based on the amount of copper in the aqueous liquid phase. The evaluation method including the above. [Effects of the Invention]

[0009] This technology can enhance the bioavailability of copper in nutritional compositions. This, in turn, increases the value of the nutritional composition. Furthermore, it enables efficient copper supplementation through this nutritional composition. Furthermore, the effects of this technology are not limited to those described herein, but may include any of the effects described in this specification. [Brief explanation of the drawing]

[0010] [Figure 1] It is a diagram for explaining the production of lysinoalanine. [Figure 2] It is a diagram for explaining a method for measuring the bioavailability of copper. [Figure 3] It is a graph plotting the measurement results of lysinoalanine content and the bioavailability of copper.

Embodiments for Carrying Out the Invention

[0011] The preferred embodiments of the present technology will be described below. However, the present technology is not limited to only the following preferred embodiments and can be freely changed within the scope of the present technology.

[0012] The nutritional composition of the present technology contains a protein component and copper. The nutritional composition contains lysinoalanine at a content of 3,000 μg or less per 1 g of the protein component, and contains the copper at a content of 0.01 mg or more per 100 g of the nutritional composition. By controlling the lysinoalanine content in this way, the bioavailability of the copper contained in the nutritional composition of the present technology can be enhanced. Therefore, the nutritional composition of the present technology is particularly suitable for humans who require copper supplementation. The lysinoalanine content can be controlled by, for example, adjusting the type of the protein component and / or the treatment conditions in the sterilization process as described below.

[0013] The present technology also provides a method for producing the nutritional composition. The production method includes, for example, a preparation step of preparing a mixture containing the protein component and the copper, and a sterilization step of sterilizing the mixture. In a preferred embodiment, the sterilization step is performed such that the lysinoalanine content of the nutritional composition does not exceed 3,000 μg per 1 g of the protein component. As described below, the lysinoalanine content can be controlled in this way by adjusting the composition of the mixture and / or by adjusting the conditions of the sterilization step. Further, by controlling the lysinoalanine content in the nutritional composition in this way, the bioavailability of the copper contained in the nutritional composition can be improved.

[0014] The present technology also provides a method for evaluating the bioavailability of copper in a nutritional composition containing a protein component and copper. The evaluation method includes a digestion step of subjecting the nutritional composition to a digestion treatment using a digestive enzyme to obtain a digestive fluid, a separation step of separating the digestive fluid into at least an aqueous liquid phase and a precipitate phase by centrifugation, and an evaluation step of evaluating the bioavailability of the copper in the nutritional composition based on the amount of copper in the aqueous liquid phase. By this evaluation method, the nutritional composition can be evaluated from the viewpoint of the bioavailability of copper. For example, a nutritional composition having better bioavailability of copper can be selected.

[0015] Hereinafter, the composition of the present technology will be described in more detail.

[0016] (1) Protein component The nutritional composition of the present technology contains a protein component. The protein component is a protein, a protein hydrolyzate, or a combination of a protein and a protein hydrolyzate. The protein component may further contain amino acids.

[0017] The protein may be an animal protein or a plant protein, or both of them. The aforementioned animal protein may include, for example, one or more of milk protein, egg protein, and collagen. The milk protein may be casein, whey protein, or both. The milk protein may be incorporated into the nutritional composition as a caseinate such as sodium caseinate or calcium caseinate, acid casein, micellar casein concentrate such as micellar casein concentrate (MCC) or micellar casein isolate (MCI), milk protein concentrate (MPC), whey protein concentrate (WPC), or whey protein isolate (WPI). The aforementioned plant protein may include, for example, one or more of soy protein, rice protein, and wheat protein.

[0018] The protein hydrolysates may be hydrolysates of animal protein or plant protein, or both. These hydrolysates may be, for example, hydrolysates obtained by enzymatic treatment. The aforementioned animal protein hydrolysates may include, for example, one or more of milk protein hydrolysates, egg protein hydrolysates, and collagen hydrolysates. More specifically, the milk protein hydrolysates may be casein hydrolysates, whey protein hydrolysates, or both. The casein hydrolysates may contain casein peptides. The whey protein hydrolysates may contain whey peptides. Thus, protein hydrolysates may contain peptides, particularly peptides produced by protein degradation. The aforementioned plant protein hydrolysate may include, for example, one or more of soy protein hydrolysate, rice protein hydrolysate, and wheat protein hydrolysate.

[0019] In a preferred embodiment of this technology, the protein component comprises one or more of the following: milk protein, collagen, soy protein, milk protein hydrolysate, collagen hydrolysate, and soy protein hydrolysate. For example, the protein component comprises casein hydrolysate or collagen hydrolysate. Such protein components can enhance the bioavailability of copper contained in the nutritional composition. These protein components are useful, for example, in reducing the lydinoalanine content in the nutritional composition, and it is believed that this reduction enhances the bioavailability of copper.

[0020] In a preferred embodiment of this technology, the protein component includes casein. The casein may be included in the nutritional composition as, for example, caseinate. The caseinate may be, for example, sodium caseinate, potassium caseinate, or calcium caseinate. The nutritional composition is generally subjected to heat treatment in the sterilization process. Casein is suitable as a protein included in a nutritional composition that is subjected to heat treatment because it has excellent heat stability.

[0021] In a particularly preferred embodiment of this technology, the protein component includes micellar casein. Micellar casein is particularly suitable for enhancing the bioavailability of copper contained in the nutritional composition.

[0022] The protein component may further contain amino acids. These amino acids are amino acids added to the nutritional composition as free amino acids, that is, they are not amino acids contained in the protein or the protein hydrolysate. In this technology, the amino acid may be, for example, an essential amino acid (one or more of isoleucine, leucine, valine, histidine, lysine, methionine, tryptophan, phenylalanine, and threonine), a non-essential amino acid (one or more of asparagine, aspartic acid, alanine, arginine, cysteine, glutamine, glutamic acid, glycine, proline, serine, and tyrosine), or both an essential amino acid and a non-essential amino acid. Furthermore, in this technology, the amino acid may be one or more branched-chain amino acids, that is, it may include one, two, or all three of valine, leucine, and isoleucine.

[0023] The protein content of the aforementioned protein component is, for example, 1g or more, 1.2g or more, or 1.4g or more per 100g of the nutritional composition, preferably 2g or more, and more preferably 3g or more. This allows for efficient protein intake through the nutritional composition. The content of the protein component may be, for example, 15g or less, preferably 12g or less, more preferably 10g or less, 8g or less, or 6g or less per 100g of the nutritional composition. As the content of the protein component increases, the content of lydinoalanine may increase. Therefore, by keeping the content of the protein component below the above upper limit, this possibility can be reduced. The content of the protein component is obtained by multiplying the nitrogen content contained in the nutritional composition by the nitrogen-to-protein conversion factor for each protein component based on the "Standard Tables of Food Composition in Japan 2020 (8th Revised Edition)". The nitrogen content can be quantified, for example, based on the "Analytical Methods for Nutritional Components, etc." (hereinafter referred to as "Analytical Methods in Food Labeling Standards") of the "Food Labeling Standards (Shoshoku No. 139, March 30, 2015)", i.e., using the Kjeldahl method.

[0024] For example, the protein component includes casein, and the casein content may be, for example, 0.5g or more per 100g of the nutritional composition, preferably 1g or more, more preferably 2g or more, and even more preferably 3g or more. In this case, the casein content may be, for example, 15g or less per 100g of the nutritional composition, preferably 12g or less, and more preferably 10g or less.

[0025] Furthermore, for example, the protein component may include micellar casein, and the content of the micellar casein may be, for example, 1 g or more, preferably 2 g or more, and more preferably 3 g or more per 100 g of the nutritional composition. In this case, the content of the micellar casein may be, for example, 15 g or less, preferably 12 g or less, and more preferably 10 g or less per 100 g of the nutritional composition.

[0026] (2) Lydinoalanine

[0027] The nutritional composition of this technology contains lysinoalanine in an amount of 3,000 μg or less per gram of the protein component. More preferably, the nutritional composition contains lysinoalanine in an amount of 2,700 μg or less per gram of the protein component, and even more preferably in amounts of 2,300 μg or less, 2,000 μg or less, 1,500 μg or less, 1,000 μg or less, or 600 μg or less. By controlling the lysinoalanine content per gram of protein component in this way, the bioavailability of copper in the nutritional composition can be increased. The lydinoalanine content of the nutritional composition of this technology may be, for example, 0 μg or more per gram of the protein component, and in particular may be 1 μg or more, 10 μg or more, or 100 μg or more.

[0028] Lydinoalanine is produced by reactions involving multiple amino acids, either within the peptide chain of a protein or in the free. As shown in Figure 1, dehydroalanine is produced by β-elimination of cystine, cysteine, phosphoserine, or serine. Lysine then binds to this dehydroalanine to produce lydinoalanine. When these reactions occur between peptide chains of a protein, a cross-linking structure by lydinoalanine is formed within or between protein molecules. The dehydroalanine mentioned above also reacts with other amino acids to produce various substances that can form crosslinks. For example, when dehydroalanine reacts with cysteine, lanthionine is produced, and similarly, when it reacts with histidine, histidinoalanine is produced. Nutritional compositions containing protein generally undergo a sterilization process, and lydinoalanine is generated during the heat treatment in this sterilization process. By controlling the lydinoalanine content per gram of protein component in the nutritional composition, the bioavailability of copper contained in the nutritional composition can be improved. Furthermore, in the sterilization process, the amount of substances produced by the reaction of other amino acids and dehydroalanine as described above may be controlled, and the bioavailability of copper can also be improved by suppressing such production.

[0029] In this specification, the lydinoalanine content per gram of protein component is measured by weighing a fixed amount of the protein component, hydrolyzing it with hydrochloric acid, evaporating it, dissolving it in a fixed amount of 0.02N hydrochloric acid, and quantifying it by LC-MS using deuterated lysine as an internal standard. Details of this measurement method are described in the following examples within this specification.

[0030] (3)Copper The nutritional composition of this technology contains copper. The nutritional composition may contain copper in an amount of 0.01 mg or more per 100 g of the nutritional composition, preferably 0.03 mg or more, and more preferably 0.05 mg or more. Such a content can increase the amount of copper absorbed by the body, and the effects of copper intake can be more strongly exerted. The copper content may be, for example, 1 mg or less, 0.8 mg or less, or 0.5 mg or less per 100 g of the nutritional composition.

[0031] The copper content is measured by subjecting the evaluation sample to ICP-MS after pretreatment by wet decomposition. Details of the method for measuring the copper content are described in the following examples in this specification as part of the method for measuring the bioavailability of copper.

[0032] The copper may be incorporated into the nutritional composition as a component of a copper-containing additive that can be incorporated into the nutritional composition. Examples of such copper-containing additives include copper gluconate, copper-containing mineral yeast, or copper sulfate. The nutritional composition of this technology may contain such a copper-containing additive.

[0033] In one embodiment of this technology, the nutritional composition contains copper gluconate. The copper gluconate content is, for example, 0.05 mg or more per 100 g of the nutritional composition, preferably 0.1 mg or more, and more preferably 0.2 mg or more. The copper gluconate content is, for example, 1.5 mg or less per 100 g of the nutritional composition, preferably 1.2 mg or less, and more preferably 1.0 mg or less. The copper gluconate content may be adjusted as appropriate based on the desired copper content. Furthermore, even if the nutritional composition is copper-containing mineral yeast or copper sulfate, the content of these components may be adjusted as appropriate based on the desired copper content.

[0034] (4) Other ingredients The nutritional composition of this technology may further contain other components. Examples of such other components include carbohydrates, dietary fiber, vitamins, minerals, oils and fats, and other nutritional components. The nutritional composition of this technology may contain one or more of these other components. Furthermore, the other ingredients may include one or more additives selected from emulsifiers, thickeners, and gelling agents. These other components may be appropriately selected depending on, for example, the target recipient or purpose of administration of the nutritional composition, or the form or physical properties of the nutritional composition.

[0035] (Carbohydrates) The aforementioned carbohydrates may include carbohydrates that can be added to food, such as monosaccharides, disaccharides, oligosaccharides, and polysaccharides. For example, the disaccharide is lactose. For example, the polysaccharide is dextrin. That is, the nutritional composition may contain, for example, lactose and / or dextrin.

[0036] The content of the carbohydrates (particularly lactose and / or dextrin) may be, for example, 5g or more, 7g or more, 10g or more, preferably 12g or more, and more preferably 15g or more per 100g of the nutritional composition. Alternatively, the content of the carbohydrates (particularly lactose and / or dextrin) may be, for example, 50g or less, preferably 40g or less, and more preferably 30g or less per 100g of the nutritional composition.

[0037] (Dietary fiber) The dietary fiber may include water-soluble and insoluble dietary fiber, which are dietary fibers that can be added to food. Examples of water-soluble dietary fiber include indigestible dextrin, inulin, and guar gum hydrolysate. Examples of insoluble dietary fiber include cellulose. In other words, the nutritional composition may include, for example, indigestible dextrin and inulin.

[0038] The dietary fiber content may be, for example, 0.1g or more, preferably 0.5g or more, and more preferably 0.7g or more per 100g of the nutritional composition. Furthermore, the nutritional composition of this technology may contain dietary fiber in an amount of, for example, 6g or less, 5g or less, 4g or less, 3g or less, preferably 2g or less, and more preferably 1.5g or less per 100g of the nutritional composition.

[0039] (Vitamins) The aforementioned vitamins may include, for example, one or more of the following: vitamin A, vitamin B (e.g., vitamin B1, vitamin B2, vitamin B6, niacin, pantothenic acid, biotin, vitamin B12, folic acid, etc.), vitamin C, vitamin D, vitamin E, and vitamin K.

[0040] The vitamins preferably include water-soluble vitamins, and more particularly vitamin C. The content of the water-soluble vitamins (especially vitamin C) may be, for example, 0.005g or more, 0.01g or more, preferably 0.02g or more, and more preferably 0.03g or more per 100g of the nutritional composition. Alternatively, the content of the water-soluble vitamins (especially vitamin C) may be, for example, 0.20g or less, preferably 0.15g or less, and more preferably 0.10g or less per 100g of the nutritional composition.

[0041] (Minerals) Examples of the aforementioned minerals include mineral-containing compounds that include minerals other than copper. Examples of the aforementioned mineral-containing compounds include sodium-containing compounds, potassium-containing compounds, calcium-containing compounds, phosphorus-containing compounds, magnesium-containing compounds, iron-containing compounds, and zinc-containing compounds. The aforementioned mineral-containing compounds may contain one or more of these compounds, or for example, all of them. Examples of the sodium-containing compounds include sodium carbonate, sodium bicarbonate, sodium chloride, and trisodium citrate, disodium hydrogen phosphate, sodium dihydrogen phosphate, and sodium hydroxide. The sodium-containing compound may be any one, two, or three of these. Examples of the potassium-containing compounds include potassium chloride, potassium carbonate, and dipotassium hydrogen phosphate and potassium dihydrogen phosphate. The potassium-containing compound may be one or two of these. Examples of the calcium-containing compounds include calcium hydroxide, calcium carbonate, tricalcium phosphate, eggshell calcium, seashell calcium, and calcium chloride. The calcium-containing compound may be one or two of these. Examples of the phosphorus-containing compound include phosphoric acid, potassium dihydrogen phosphate, dipotassium hydrogen phosphate, and tripotassium phosphate, tricalcium phosphate, disodium hydrogen phosphate, and disodium hydrogen phosphate. The phosphorus-containing compound may be any one, two, or three of these. Examples of the magnesium-containing compound include magnesium chloride, trimagnesium phosphate, magnesium hydroxide, magnesium oxide, and magnesium carbonate. The magnesium-containing compound may be any one, two, or three of these. Examples of the iron-containing compounds include sodium ferrous citrate, ferric chloride, iron citrate, ammonium iron citrate, ferrous gluconate, iron lactate, ferric pyrophosphate, and ferrous sulfate. The iron-containing compounds may consist of one, two, or three or more of these compounds. Examples of the zinc-containing compounds include zinc gluconate, zinc sulfate, and zinc yeast. The zinc-containing compound may be one or two of these.

[0042] (oils and fats) As the aforementioned oils and fats, for example, vegetable-derived oils such as soybean oil or rapeseed oil may be used. By including the aforementioned oils and fats in the nutritional composition, efficient energy intake becomes possible. If the nutritional composition contains oils and fats, the nutritional composition may be emulsified, for example, to form an oil-in-water emulsion. For this emulsification, the nutritional composition may further contain an emulsifier.

[0043] The content of the oils and fats may be, for example, 0.5g or more, preferably 1.0g or more, and more preferably 1.5g or more, per 100g of the nutritional composition. Alternatively, the content of the oils and fats may be, for example, 7.0g or less, 6.0g or less, or 5.0g or less, preferably 4.5g or less, and more preferably 4.0g or less, per 100g of the nutritional composition.

[0044] As the emulsifier, one or more combinations of glycerin fatty acid esters (glycerin esters), saponins, sucrose fatty acid esters, lecithin, and enzymatically hydrolyzed lecithin may be used. In a preferred embodiment, the emulsifier comprises a glycerol fatty acid ester and lecithin. Examples of glycerol fatty acid esters include monoglycerides, organic acid monoglycerides, and polyglycerol fatty acid esters, and particularly include organic acid monoglycerides. The organic acid monoglyceride may be one or more of the following: monoglyceride acetate, monoglyceride lactate, monoglyceride citrate, monoglyceride diacetyltartaric acid, and monoglyceride succinic acid.

[0045] The amount of the emulsifier may be, for example, 0.01 g or more, preferably 0.02 g or more, and more preferably 0.05 g or more, per 100 g of the nutritional composition of this technology. The amount of the emulsifier may be, for example, 1 g or less, 0.5 g or less, preferably 0.4 g or less, and more preferably 0.2 g or less, per 100 g of the nutritional composition of this technology.

[0046] (Thickening agent) As the thickening agent, one or more of the following may be used: xanthan gum, gellan gum, guar gum, locust bean gum, carrageenan, agar, pectin, and sodium alginate. The thickening agent may impart to the nutritional composition of this technology physical properties other than liquid, such as a viscous or semi-solid state, or it may impart to gastric viscosity properties. The thickening agent is also called a gelling agent when used to gel the composition. By obtaining these physical properties, the nutritional composition produced using this technology can exhibit the effects expected from a nutritional composition with adjusted physical properties, such as adjusting the administration rate and preventing reflux and diarrhea. Furthermore, while the use of thickeners can potentially reduce mineral utilization, this technology can improve copper utilization, thus preventing the reduction in mineral utilization caused by the use of thickeners.

[0047] The amount of the thickening agent may be, for example, 0.01 g or more, preferably 0.05 g or more, and more preferably 0.1 g or more, per 100 g of the nutritional composition of this technology. The amount of the thickening agent may be, for example, 5 g or less, 3 g or less, preferably 2 g or less, and more preferably 1 g or less, per 100 g of the nutritional composition of this technology.

[0048] The nutritional composition of this technology may contain, for example, water, sweeteners, fruit juice, vegetable juice, flavorings, colorings, and acidulants. The types and proportions of these components may be appropriately selected by those skilled in the art according to the desired physical properties, shape, taste, or appearance.

[0049] The water content in the nutritional composition of this technology may be, for example, 50g or more, preferably 55g or more, and more preferably 60g or more, per 100g of the nutritional composition. Alternatively, the water content may be, for example, 90g or less, 88g or less, or 85g or less, preferably 80g or less, and more preferably 75g or less, per 100g of the nutritional composition.

[0050] (5) Physical properties of nutritional composition The nutritional composition of this technology is fluid and may be, for example, a liquid or paste, or a fluid gel. The fluidity makes the nutritional composition easier to consume, for example, by patients or the elderly.

[0051] The nutritional composition of this technology may be in an emulsified state, preferably an oil-in-water emulsion (O / W type). If the nutritional composition of this technology contains oils or fats, it is desirable that the nutritional composition be emulsified.

[0052] The nutritional composition of this technology may preferably contain 10% or more, more preferably 15% or more, even more preferably 20% or more, 25% or more, or 30% or more of copper in terms of bioavailability. The bioavailability of the aforementioned copper is the ratio of the amount of copper released into the aqueous liquid phase by gastric digestion of the nutritional composition in artificial digestion to the amount of copper contained in the nutritional composition before gastric digestion, and can be calculated using the following formula. (Bioavailability (unit: %)) = (Amount of copper released into the aqueous liquid phase by gastric digestion of the nutritional composition) / (Amount of copper contained in the nutritional composition before gastric digestion) × 100 Details of the method and formula for measuring the bioavailability of the aforementioned copper are described in the examples below.

[0053] The osmotic pressure of the nutritional composition of this technology may be, for example, 100 mOsm / L or more, preferably 150 mOsm / L or more. Alternatively, the osmotic pressure may be, for example, 700 mOsm / L or less, preferably 650 mOsm / L or less, and more preferably 400 mOsm / L or less.

[0054] The pH of the nutritional composition of this technology at 20°C may be, for example, 8.0 or less, 7.5 or less, 7.0 or less, 6.5 or less, or 6.0 or less. Alternatively, the pH may be 3.0 or higher, 4.0 or higher, or 5.0 or higher.

[0055] The specific gravity of the nutritional composition of this technology at 20°C may be, for example, 0.8 to 1.5, preferably 0.9 to 1.4, and more preferably 1.0 to 1.2.

[0056] The viscosity of the nutritional composition of this technology at 20°C is, for example, 1 mPa·s or more, 10 mPa·s or more, 100 mPa·s or more, or 1000 mPa·s or more, and more preferably 10000 mPa·s or more. Furthermore, with respect to the gastric viscosity-enhancing nutritional composition, when the nutritional composition is mixed with artificial gastric fluid, the viscosity at 20°C when the ratio of artificial gastric fluid to the nutritional composition is, for example, 25% by mass, 40% by mass, 50% by mass, and 75% by mass, may be, for example, 4,000 mPa·s or more, and more preferably 10,000 mPa·s or more. The gastric viscosity-enhancing nutritional composition may be, for example, 4,000 mPa·s or less, preferably 1,000 mPa·s or less, before ingestion (i.e., before mixing with artificial gastric fluid). The viscosity of the nutritional composition can be measured using a Type B rotational viscometer (measurement temperature: 20°C, rotor speed: 6 rpm). Furthermore, the gastric thickening property of the nutritional composition can be evaluated by measuring the viscosity of a mixture obtained by combining the nutritional composition with artificial gastric fluid. The above artificial gastric juice can be prepared according to the "6.09 Disintegration Test Method" of the 17th edition of the Japanese Pharmacopoeia (pH 1.2, sodium chloride 2.0 g / L, hydrochloric acid 7.0 ml / L).

[0057] In one embodiment of this technology, the energy content per gram of the nutritional composition of this technology may be 0.4 kcal or more, 0.5 kcal or more, 0.6 kcal or more, 0.7 kcal or more, 0.8 kcal or more, or 0.9 kcal or more. Thus, a high energy content per gram of the composition enables efficient energy intake. In this embodiment, the energy content per gram of the nutritional composition of this technology may be, for example, 5 kcal or less, 4 kcal or less, 3 kcal or less, 2 kcal or less, or 1.8 kcal or less.

[0058] (6) Food and drink composition The nutritional composition of this technology may be used as a food or beverage composition. That is, this technology also provides a nutritional composition that is a food or beverage composition. The food or beverage composition may have, for example, a liquid or paste form, or it may be a fluid gel.

[0059] The food and beverage composition of this technology may be used as an oral or enteral nutritional supplement. The food and beverage composition of this technology can be provided or sold as a food or beverage labeled with its intended use, for example, for providing nutrition to people who require protein supplementation, for providing nutrition to people who require copper supplementation, or for providing nutrition to people who are concerned about copper deficiency. Furthermore, the food and beverage composition of this technology can be provided and / or sold with labeling indicating the target audience, for example, "people who require protein supplementation," "people who require copper supplementation," or "people who are concerned about copper deficiency."

[0060] The food and beverage compositions of this technology may be consumed by healthy individuals, or by individuals with a disease or those at risk of developing a disease. An example of such a disease is copper deficiency. For example, premature infants, infants recovering from severe malnutrition, or infants suffering from persistent diarrhea are at risk of copper deficiency. Adults with diseases that inhibit nutrient absorption (such as celiac disease, Crohn's disease, cystic fibrosis, and tropical sprue, which cause malabsorption), adults after weight-loss surgery (bariatric surgery), and adults who have taken excessive amounts of zinc (which reduces copper absorption) are also at risk of copper deficiency. The food and beverage compositions of this technology may be used to prevent or address copper deficiency in such humans. Furthermore, dialysis patients may also suffer from copper deficiency. Dialysis patients may experience reduced copper intake due to, for example, phosphorus restriction, or inhibited copper absorption due to zinc supplementation, and in such cases, copper deficiency may occur. Therefore, the food and beverage compositions of this technology may be used to prevent or address copper deficiency in dialysis patients. Furthermore, patients receiving tube feeding, especially those receiving long-term tube feeding, may also suffer from copper deficiency. Therefore, the food and beverage compositions of this technology may be used for consumption by patients receiving tube feeding. They may be used to prevent or address copper deficiency in patients receiving tube feeding.

[0061] The act of "displaying" includes all acts that inform consumers of the uses of the composition of this technology, and any expression that can evoke and / or infer the said uses, regardless of the purpose of the display, the content of the display, the object and / or medium on which it is displayed, all of these constitute an act of "displaying" this technology.

[0062] Furthermore, it is preferable that the "display" be made in a way that allows consumers to directly recognize the above-mentioned use. Specifically, this includes acts such as transferring, delivering, displaying for transfer or delivery, or importing food and beverage products or product packaging on which the above-mentioned use is described; displaying or distributing advertisements, price lists, or transaction documents related to products on which the above-mentioned use is described; or providing information containing such information on an electronic (internet, etc.) basis.

[0063] On the other hand, the content of the display is preferably a display approved by the government or other administrative body (for example, a display approved based on various systems established by the government and made in accordance with such approval). Furthermore, it is preferable to attach such display content to packaging, containers, catalogs, brochures, point-of-sale (POP) displays and other promotional materials used at sales sites, and other documents.

[0064] Furthermore, "labeling" also includes labeling as health foods, functional foods, enteral nutrition foods, foods for special dietary uses, health functional foods, foods for specified health uses, nutrient functional foods, foods with functional claims, quasi-drugs, etc.

[0065] (7) Pharmaceutical composition The nutritional composition of this technology may be used as a pharmaceutical composition. That is, this technology also provides a nutritional composition that is a pharmaceutical composition. The pharmaceutical composition may have, for example, a liquid or paste form, or it may be a fluid gel.

[0066] The pharmaceutical composition of this technology may be used, for example, to prevent copper deficiency in humans, or to treat humans who are copper deficient. Such humans are, for example, those who are at risk of developing copper deficiency or who are already suffering from copper deficiency. Such humans who are at risk of developing copper deficiency are as described in (6) above. The pharmaceutical composition of this technology may be used for administration to such humans.

[0067] When the composition relating to this technology is used as a pharmaceutical composition, it may be administered orally or parenterally, and can be formulated into a desired dosage form as appropriate depending on the method of administration. For example, in the case of oral administration, it may be formulated into a desired dosage form (liquid or paste). In the case of parenteral administration, the composition relating to this technology can be administered, for example, via a nasogastric tube, gastrostomy, or jejunostomy.

[0068] Furthermore, when formulating, the pharmaceutical composition relating to this technology may contain additives commonly used in formulation (e.g., pH adjusters, colorants, flavoring agents, etc.). In addition, the pharmaceutical composition relating to this technology may contain known or potentially discovered components for improving the condition of acutely ill patients, as long as they do not impair the effects of this technology. In addition, formulation can be carried out by known methods as appropriate, depending on the dosage form. When formulating, a formulation carrier may be added as appropriate.

[0069] (8) Method for producing nutritional composition The method for producing the nutritional composition of this technology includes a preparation step of preparing a mixture containing the protein component and the copper, and a sterilization step of sterilizing the mixture. These steps will be described below.

[0070] In the preparation step described above, the protein component and the copper are mixed. For example, an aqueous solution containing the protein component and an aqueous solution containing the copper are prepared. These aqueous solutions are then mixed to obtain a mixture. Other components contained in the nutritional composition (as described in (3) above) may also be added to this mixture. In this way, a mixture to be subjected to the sterilization step is prepared.

[0071] In one embodiment, the preparation step may include further mixing the oils and fats (and the emulsifier) ​​into a mixture of an aqueous solution containing a protein component and an aqueous solution containing copper. The preparation step may further include an emulsification process to emulsify the mixture after the mixing. That is, in this embodiment, an emulsion containing a protein component and copper may be prepared in the preparation step. The emulsion may then be subjected to the following sterilization step.

[0072] Preferably, the preparation step may include adjusting the pH of the mixture (e.g., the emulsion). The pH is preferably adjusted to 6.5 or less, more preferably 6.4 or less, and even more preferably 6.3 or less. A nutritional composition produced from a mixture having a pH below such an upper limit, through the following sterilization step, exhibits excellent bioavailability. The pH of the mixture is adjusted to, for example, 3.0 or higher, 4.0 or higher, or 5.0 or higher. If the pH is too low, adverse effects may occur, such as the denaturation of components in the mixture (e.g., protein components). To adjust the pH of the mixture (e.g., the emulsion), pH adjusters known in the art may be used. The pH adjuster may be, for example, an organic acid, an inorganic acid, or a combination thereof. The organic acid may be, for example, one or more combinations of malic acid, citric acid, tartaric acid, succinic acid, ascorbic acid, lactic acid, gluconic acid, and acetic acid. The inorganic acid may be, for example, one or more combinations of hydrochloric acid, phosphoric acid, carbonic acid, and nitric acid.

[0073] In the sterilization step, the mixture prepared in the preparation step is sterilized. The sterilization step is performed so that the lydinoalanine content of the nutritional composition does not exceed 3000 μg per gram of protein component. By controlling the lydinoalanine content in this way, the bioavailability of copper in the nutritional composition after the sterilization step can be increased. Furthermore, the pH of the mixture subjected to the sterilization process may be adjusted to within the numerical range described in relation to the preparation step. By subjecting the pH-adjusted mixture to the sterilization step in this manner, the bioavailability of copper in the resulting nutritional composition can be improved.

[0074] Preferably, the sterilization step is carried out such that the mixture is maintained at 100°C or higher for 3 minutes or less, 2 minutes or less, or 1 minute or less. By maintaining the high temperature for such a short time, the formation of lydinoalanine can be prevented. To perform such short-time sterilization, methods such as high-temperature short-time sterilization (HTST), ultra-high temperature sterilization (UHT), or pressurized heat sterilization may be employed. HTST and UHT may be performed, for example, by direct heat sterilization or indirect heat sterilization. Direct heat sterilization may be performed by injection or infusion, and indirect heat sterilization may be performed by plate or tubular methods.

[0075] The manufacturing method described above may further include a filling step of filling a container with the composition obtained in the mixing step, either before or after the sterilization step. If the filling step is performed after the sterilization step, the filling step may be performed aseptically. The container may be, for example, a paper carton, a plastic bag, a plastic bottle, a plastic cup, an aluminum pouch, a metal can, or a glass container. The filling step results in the nutritional composition being filled into a container. The nutritional composition of this technology may be sold in a filled container.

[0076] (9) Method of using nutritional composition The target recipients of the nutritional composition of this technology may be animals, particularly mammals, more particularly primates, and even more particularly humans or non-human primates, and especially preferably humans. When the target recipient of the composition of this technology is a human, the age of the human may be, for example, 0 to 120 years. For example, the nutritional composition of this technology may be administered to the target recipients as described in (6) or (7) above. Furthermore, the nutritional composition of this technology may be administered in any of the uses described in (6) or (7) above.

[0077] The nutritional composition of this technology may be administered, for example, orally or enterally. In the latter case, the nutritional composition of this technology is administered to humans, for example, via a nasogastric tube, gastrostomy, or jejunostomy. The composition of this technology may be fluid, which facilitates oral intake. Furthermore, this fluidity makes it suitable for enteral administration to patients receiving enteral nutrition.

[0078] (10) Examples of nutritional composition of nutritional composition An example of the nutritional composition of the nutritional composition of this technology is described below. The nutritional composition of this technology contains a protein component (particularly casein), and the amount of said protein component may be as described in (1) above. The nutritional composition of this technology contains fat in an amount of, for example, 0.5 g or more, preferably 1 g or more, and more preferably 1.5 g or more per 100 g of the nutritional composition. Furthermore, the nutritional composition of this technology contains fat in an amount of, for example, 5 g or less, preferably 4.5 g or less, and more preferably 4 g or less per 100 g of the nutritional composition. The nutritional composition of this technology may contain carbohydrates. The amount of such carbohydrates may be, for example, as described in (4) above. The nutritional composition of this technology may contain dietary fiber. The amount of dietary fiber may be, for example, as described in (4) above. The nutritional composition of this technology contains ash in an amount of, for example, 0.1g or more, preferably 0.2g or more, and more preferably 0.3g or more per 100g of the nutritional composition. Furthermore, the nutritional composition of this technology contains ash in an amount of, for example, 1.5g or less, preferably 1.2g or less, and more preferably 1.0g or less per 100g of the nutritional composition. The nutritional composition of this technology contains solids in an amount of, for example, 10g or more, preferably 15g or more, and more preferably 20g or more per 100g of the nutritional composition. Furthermore, the nutritional composition of this technology contains solids in an amount of, for example, 40g or less, preferably 30g or less, and more preferably 25g or less per 100g of the nutritional composition. The nutritional composition of this technology contains sodium (Na) in an amount of, for example, 10 mg or more, 15 mg or more, 50 mg or more, preferably 100 mg or more, and more preferably 150 mg or more per 100 g of the nutritional composition. Furthermore, the nutritional composition of this technology contains sodium in an amount of, for example, 400 mg or less, preferably 300 mg or less, and more preferably 250 mg or less per 100 g of the nutritional composition. The nutritional composition of this technology contains potassium (K) in an amount of, for example, 30 mg or more, preferably 50 mg or more, and more preferably 70 mg or more per 100 g of the nutritional composition. Furthermore, the nutritional composition of this technology contains potassium in an amount of, for example, 300 mg or less, preferably 250 mg or less, and more preferably 200 mg or less per 100 g of the nutritional composition. The nutritional composition of this technology contains calcium (Ca) in an amount of, for example, 10 mg or more, preferably 20 mg or more, and more preferably 40 mg or more per 100 g of the nutritional composition. Furthermore, the nutritional composition of this technology contains calcium in an amount of, for example, 150 mg or less, preferably 120 mg or less, and more preferably 100 mg or less per 100 g of the nutritional composition. The nutritional composition of this technology contains phosphorus (P) in an amount of, for example, 10 mg or more, preferably 20 mg or more, and more preferably 40 mg or more per 100 g of the nutritional composition. Furthermore, the nutritional composition of this technology contains phosphorus in an amount of, for example, 150 mg or less, preferably 120 mg or less, and more preferably 100 mg or less per 100 g of the nutritional composition. The nutritional composition of this technology contains magnesium (Mg) in an amount of, for example, 5 mg or more, preferably 10 mg or more, and more preferably 20 mg or more per 100 g of the nutritional composition. Furthermore, the nutritional composition of this technology contains magnesium in an amount of, for example, 80 mg or less, preferably 60 mg or less, and more preferably 50 mg or less per 100 g of the nutritional composition. The nutritional composition of this technology contains chlorine (Cl) in an amount of, for example, 30 mg or more, 40 mg or more, 50 mg or more, preferably 100 mg or more, and more preferably 150 mg or more per 100 g of the nutritional composition. Furthermore, the nutritional composition of this technology contains chlorine in an amount of, for example, 400 mg or less, preferably 300 mg or less, and more preferably 250 mg or less per 100 g of the nutritional composition. The nutritional composition of this technology contains iron (Fe) in an amount of, for example, 0.2 mg or more, preferably 0.5 mg or more, and more preferably 0.8 mg or more per 100 g of the nutritional composition. Furthermore, the nutritional composition of this technology contains iron in an amount of, for example, 2.0 mg or less, preferably 1.8 mg or less, and more preferably 1.5 mg or less per 100 g of the nutritional composition. The nutritional composition of this technology contains zinc (Zn) in an amount of, for example, 0.3 mg or more, preferably 0.6 mg or more, and more preferably 1.0 mg or more per 100 g of the nutritional composition. Furthermore, the nutritional composition of this technology contains zinc in an amount of, for example, 3.0 mg or less, preferably 2.5 mg or less, and more preferably 2.0 mg or less per 100 g of the nutritional composition. The nutritional composition of this technology contains copper (Cu), and the amount of copper may be as described above.

[0079] (11) Method for evaluating the bioavailability of copper in nutritional compositions This technology also provides a method for evaluating the bioavailability of copper in a nutritional composition. The evaluation method may include a digestion step of subjecting a nutritional composition containing protein components and copper to digestion using digestive enzymes to obtain a digestate; a separation step of separating the digestate so that at least two phases, including an aqueous liquid phase, are formed; and an evaluation step of evaluating the bioavailability of copper in the nutritional composition based on the amount of copper in the aqueous liquid phase. By performing these steps, the bioavailability of copper in a nutritional composition can be appropriately evaluated.

[0080] Each step included in the evaluation method according to this technology is described below.

[0081] In the digestion process described above, a nutritional composition containing protein components and copper is subjected to digestion using digestive enzymes. Digestive fluid is obtained by this digestion process. The digestive enzyme is preferably an intragastric digestive enzyme, and more specifically, pepsin. The digestion process may include, for example, dissolving the nutritional composition in water and adding digestive enzymes to the resulting solution. The solution obtained by dissolving the nutritional composition in water may be adjusted to a pH of, for example, 1 to 3, particularly 1.5 to 2.5. Alternatively, the digestion process may include dissolving the nutritional composition in water containing digestive enzymes. The resulting solution may be adjusted to a pH of, for example, 1 to 3, particularly 1.5 to 2.5. In the digestion process described above, the state in which the nutritional composition is in contact with digestive enzymes is maintained for a predetermined time. The predetermined time may be set appropriately depending on the type of nutritional composition or the expected duration of gastric dwell time. The predetermined time may be, for example, 30 minutes to 5 hours, particularly 1 hour to 3 hours, and in one embodiment 2 hours. The digestion process may be carried out at, for example, 30°C to 40°C, particularly 35°C to 40°C, and in one embodiment 37°C.

[0082] The separation step may be carried out, for example, by centrifugation. The centrifugation may be carried out at a range of, for example, 2000 × g to 100000 × g, more particularly 5000 × g to 75000 × g, and more particularly 10000 × g to 50000 × g. The time spent on the centrifugation may be, for example, 10 minutes to 60 minutes, more particularly 30 minutes to 50 minutes. In the separation step, for example, the digestate may be separated into at least an aqueous liquid phase and a precipitate phase, for example, into three phases: an oil phase, an aqueous liquid phase, and a precipitate phase, or into two phases: an aqueous liquid phase and a precipitate phase. In addition, in the separation step, it may be separated into two phases: an oil phase and an aqueous liquid phase. In the separation step described above, the resulting aqueous liquid phase is recovered. The amount of copper contained in this aqueous liquid phase is used to evaluate the bioavailability of copper.

[0083] In the evaluation step, the bioavailability of copper in the nutritional composition is evaluated based on the amount of copper in the aqueous liquid phase. For example, the copper concentration in the aqueous liquid phase may be quantified in the evaluation step. To determine the amount of copper (particularly to quantify the copper concentration), mass spectrometry may be performed, for example, inductively coupled plasma mass spectrometry (also known as ICP-MS). Furthermore, the amount of copper contained in the entire nutritional composition may be referenced in the evaluation step. For example, in the evaluation step, the bioavailability of copper in the nutritional composition may be evaluated based on the amount of copper contained in the entire nutritional composition and the amount of copper in the aqueous liquid phase. Mass spectrometry may be performed to determine the amount of copper contained in the entire nutritional composition (particularly to determine the copper concentration in the nutritional composition), for example, ICP-MS may be performed. The index representing the bioavailability of copper may be an index (particularly an index shown by a numerical value) calculated using, for example, "(amount of copper released into the aqueous liquid phase by gastric digestion of the nutritional composition) / (amount of copper contained in the nutritional composition before gastric digestion)". In the evaluation process described above, the amount of copper may be a quantified amount, but alternatively, data that indirectly represents the amount of copper, such as intensity data from mass spectrometry results, may be used as the amount of copper. Furthermore, in the evaluation process, a numerical index (e.g., a percentage index) may be used as an indicator of the bioavailability of copper, but it is not necessary to derive a numerical index. For example, for two or more nutritional compositions, which nutritional composition has higher copper availability may be evaluated based on the amount of copper.

[0084] In one embodiment, the bioavailability of copper in the nutritional composition may be measured in the evaluation step. That is, a numerical value that serves as a measure of bioavailability may be determined, and in this case, the evaluation method may be used as a measurement method. In other words, this technology also provides a method for measuring the bioavailability of copper in a nutritional composition containing protein components and copper.

[0085] The following examples illustrate a more detailed example of the evaluation method of this technology, but the specific operating procedures in each step may be modified as appropriate depending on the type of nutritional composition.

[0086] The present technology will be described in more detail below with reference to examples, but the present technology is not limited to these examples. [Examples]

[0087] <Test 1: Changes in the bioavailability of copper> By changing the type and amount of protein, four types of nutritional compositions with different raw material formulations were established, as shown in Table 1 below. Nutritional compositions with raw material formulations A and B are standard liquid foods that do not contain thickeners, while nutritional compositions with raw material formulations C and D are thickened liquid foods that contain thickeners. Of these nutritional compositions, those with sodium caseinate as the protein source are raw material formulations A or C, and those with micellar casein concentrate (MCC) as the protein source are raw material formulations B or D. The nutritional composition of the compositions prepared according to each formulation type is shown in Table 2 below. The values ​​shown in Table 2 are per 100g of the nutritional composition.

[0088] [Table 1]

[0089] [Table 2]

[0090] Raw material compositions were prepared by mixing the raw materials according to the raw material blending type listed in Table 1. Then, each raw material composition was divided into three equal parts and treated under three different sterilization conditions: unsterilized, UHT sterilization, and retort sterilization, as described in Table 3. This resulted in the preparation of 12 different nutritional compositions with varying raw material blends and sterilization conditions. After preparation, the lydinoalanine content and copper utilization of these nutritional compositions were measured to confirm the correlation between lydinoalanine production and copper utilization. The methods for measuring lydinoalanine content and copper bioavailability (hereinafter also referred to as "copper utilization") are as follows.

[0091] <Method for measuring lysinoalanine content> (Sample preparation) A nutritional composition sample containing approximately 20 mg of protein was weighed into a glass bottle. HCl was added to achieve a final concentration of approximately 6 M, and the bottle was sealed with a butyl stopper and an aluminum cap. The inside of the glass bottle was then subjected to negative pressure by degassing. The sample was acid hydrolyzed at 110°C for 24 hours, filtered through cotton wool, and collected in a round-bottom flask for evaporative treatment. The evaporatively treated sample was dissolved in 5 mL of 0.02 N hydrochloric acid and passed through a 0.22 μm filter. 1 μg / mL of L-lysine dihydrochloride 4,4,5,5-d4 (Cambridge Isotope Laboratories, Inc.) was added to the 0.02 N hydrochloric acid as an internal standard. (LC-MS measurement) LC-MS analysis of samples was performed using solvent A (acetonitrile / formic acid = 100 / 0.3) and solvent B (100 mM ammonium formate) under gradient conditions of "85-0% A, 15-100% B (0-8 min)" and "0% A, 100% B (8-16 min)" at a flow rate of 0.6 mL / min using an Intrada Amino acid column (150 × 3 mm, Imtakt). Lydinoalanine (m / z 234.10) was quantified by correcting with L-lysine 4,4,5,5-d4 (m / z 151.0) as an internal standard.

[0092] <Method for measuring the bioavailability of copper> The nutritional composition was subjected to a digestion process simulating digestion in the stomach. In this digestion process, 40 g of MilliQ water was added to 72 g of the nutritional composition in a beaker, the pH was adjusted to 2.0 with 6 M HCl, and then more MilliQ water was added to make up to 120 g to obtain a sample to be digested. 24 g of the sample after making up was quantified into a tube, and 3 mL of pepsin solution (2% w / v pepsin, 0.1 M HCl, company name: Sigma, product number: P7000-100G) was added. After this addition, it was incubated for 2 hours at 37°C and 105 rpm in a water bath (company name: Yamato Scientific Co., Ltd., product number: BT100). After incubation, the nutritional composition was cooled with ice and centrifuged at 45,000 × g at 4°C for 40 minutes. This centrifugation formed three phases in the tube: an oil phase, an aqueous liquid phase, and a precipitate phase. Figure 2 shows a schematic diagram of the state inside the tube before and after the digestion process and centrifugation. As shown in the figure, the nutrient composition in tube T is separated into three phases: an oil phase, an aqueous liquid phase, and a precipitate phase, through the digestion process and centrifugation. Of these phases, the aqueous liquid phase was recovered through a 0.45 μm filter (Company name: Toyo Roshi Co., Ltd., Product number: DISMIC-25CS). A fixed amount (0.8 g) of the aqueous liquid phase after filtering was measured into a tube and mixed with 5 mL of 70% (v / v) nitric acid aqueous solution. Wet decomposition was then performed using a heat block (Company name: GL Sciences Co., Ltd., Product number: DigiPREP MS). Specifically, the temperature was raised from room temperature to 65°C (0-25 mins), held at 65°C for 30 minutes (25-55 mins), then raised again from 65°C to 105°C (55-80 mins), and held at 105°C for 50 minutes. At that point, the sample was removed from the heat block, hydrogen peroxide (30% v / v, 1 ml) was added, and the sample was held at 105°C for a further 20 minutes. The solution obtained after the thermal wet decomposition was diluted to 50 mL with Milli-Q water, and the copper concentration was quantified by ICP-MS (Agilent 7700x, Agilent Technologies, Santa Clara, CA, USA). The total copper concentration in the nutritional composition was also measured by subjecting the nutritional composition to ICP-MS after the same wet decomposition treatment as described above. Based on the quantified copper concentration in the aqueous liquid phase and the total copper concentration in the nutritional composition, the bioavailability of copper was calculated using the following formula. (Bioavailability (unit: %)) = (Copper concentration in aqueous liquid phase after digestion process × 27) / (Copper concentration in nutritional composition × 72 / 120 × 24) × 100 (In the formula, "27" is the value obtained by adding 3 mL (≒ 3 g) of the pepsin solution to 24 g of the sample quantified in the tube during the digestion process. "72" is the value of the amount of nutritional composition in the beaker during the digestion process. "120" is the value of the sample volume after making up with Milli-Q water during the digestion process. "24" is the value of the amount of sample quantified in the tube during the digestion process.) While the bioavailability of nutrients is generally evaluated after digestion in the intestines, copper is reported to be mainly absorbed from the duodenum after gastric digestion. Therefore, evaluating the bioavailability of copper present in the soluble portion (aqueous liquid phase) after gastric digestion is considered to better reflect actual bioavailability. Accordingly, the amount of copper present in the aqueous liquid phase after the digestion and centrifugation processes described above can be used as an indicator of the bioavailability of copper in the nutritional composition. In other words, the bioavailability in the above formula corresponds to (amount of copper released into the aqueous liquid phase by gastric digestion of the nutritional composition) / (amount of copper contained in the nutritional composition before gastric digestion) × 100.

[0093] Table 3 shows the formulation types, pH of the raw material compositions, sterilization conditions, lysinoalanine content, and copper utilization of the 12 nutritional compositions described above. It was confirmed that the lysinoalanine content in the nutritional compositions varied by changing the formulation and sterilization methods and conditions. Furthermore, among the 12 nutritional compositions, the viscosity of nutritional composition No. 011, which is a raw material formulation type A without a thickener and has been retort sterilized, was measured to be 16.4 mPa·s. In addition, the viscosity of nutritional composition No. 012, which is a raw material formulation type C containing a thickener and has been retort sterilized, was 1662 mPa·s.

[0094] [Table 3]

[0095] Furthermore, as shown in Table 3, it can be seen that copper utilization decreases as the lysinoalanine content in the nutritional composition increases. In this regard, lysinoalanine content and copper utilization were plotted. The results of this plot are shown in Figure 3. As shown in the figure, a correlation can be seen between lysinoalanine content and copper utilization.

[0096] Furthermore, the correlation between lydinoalanine content and copper utilization obtained from this study estimated that copper utilization would be approximately 10% when the lydinoalanine content per gram of protein component was around 3000 μg. Therefore, it can be seen that, for example, by setting the lydinoalanine content per gram of protein component to 3000 μg or less, the copper utilization of the nutritional composition can be increased to 10% or more. Furthermore, in order to enhance the copper utilization of the nutritional composition, the lydinoalanine content per gram of protein component is preferably 2500 μg or less, more preferably 2300 μg or less, and even more preferably 2100 μg. This makes it possible to achieve a copper utilization of 20% or more, and even more preferably 30% or more, of the nutritional composition. Furthermore, in order to further enhance the copper utilization of the nutritional composition, the lydinoalanine content per gram of protein component is preferably 1300 μg or less, more preferably 1200 μg or less, even more preferably 1100 μg or less, and particularly preferably 1000 μg or less. This makes it possible to achieve a copper utilization of 50% or more, 60% or more, and even 70% or more.

[0097] Furthermore, it is understood that UHT sterilization is preferable to retort sterilization in order to suppress the amount of lydinoalanine produced. Therefore, it is thought that the amount of lydinoalanine produced can be suppressed by maintaining the temperature above 100°C for, for example, 3 minutes or less, preferably 2 minutes or less, and more preferably 1 minute or less during sterilization. Furthermore, it is found that using micellar casein as a protein source is preferable to sodium caseinate in order to suppress the production of lydinoalanine.

[0098] <Test 2: Verification of the amount of lydinoalanine produced> In the above experiment 1, it was shown that the bioavailability of copper changes depending on the lydinoalanine content. It is thought that if the lydinoalanine content can be controlled, the bioavailability of copper can be more reliably increased. Therefore, in experiment 2, the factors that cause changes in lydinoalanine content were investigated. Specifically, the effects of raw material composition (type of protein) on lydinoalanine content and the effects of pH during sterilization on lydinoalanine content were investigated.

[0099] As nutritional compositions, we designed raw material formulations for four types of variable viscosity liquid foods, E, F, G, and H, as described in Table 4 below. Formulation types E, F, G, and H are nutritional compositions in which the protein source is sodium caseinate, hydrolyzed casein, and soy protein, respectively, or hydrolyzed collagen. The nutritional composition of the compositions prepared by each formulation type is shown in Table 5 below.

[0100] Next, the raw materials were mixed according to the respective formulation types listed in Table 4 to prepare four raw material compositions. Furthermore, three pH-adjusted samples (hereinafter referred to as E-1, E-2, or E-3, respectively) were prepared by further adding malic acid, citric acid, or hydrochloric acid to raw material formulation type E to adjust the pH of the raw material composition to 6.0. The seven raw material compositions thus obtained were each filled into containers and retort-sterilized at 123°C for 10.5 minutes to obtain nutritional compositions. Subsequently, the lysinoalanine content of the nutritional compositions was measured. The nutritional composition of raw material blend type F had a viscosity of 15,810 mPa·s at 20°C when mixed with artificial gastric juice at a ratio of 40% by mass to the nutritional composition, while its viscosity before mixing with artificial gastric juice was 30 mPa·s or less.

[0101] [Table 4]

[0102] [Table 5]

[0103] As a result, the lydinoalanine content of each sample was as shown in Table 6 below. A comparison of the results for raw material formulation types E, F, G, and H confirmed that the lydinoalanine content fluctuated depending on the protein source. Furthermore, a comparison of the results for raw material formulation types E, E-1, E-2, and E-3 showed that the lydinoalanine content could be suppressed by lowering the pH during sterilization. Regarding copper utilization, the copper utilization of raw material formulations E-1, E-2, and E-3, which have a pH of 6, was higher than that of raw material formulation type E, which has a pH of 6.8. This indicates that lowering the pH improves copper utilization. In particular, raw material formulation type H, which had a low lydinoalanine content, showed a copper utilization of over 90%.

[0104] [Table 6]

[0105] <Test 3: Verification with compositions that have changed protein and copper concentrations> In Test 2 above, the influence of raw material composition (type of protein) and pH during sterilization on lydinoalanine content was investigated as factors that cause changes in lydinoalanine content. In Test 3, compositions were prepared with altered protein and copper concentrations in the nutritional composition, and the utilization of lydinoalanine and copper was verified.

[0106] Desalted milk whey protein powder (manufactured by Mirai Co., Ltd.), milk caseinate sodium powder (manufactured by Fonterra Co., Ltd.), lactose (manufactured by Mirai Co., Ltd.), mineral mixture (manufactured by Tomita Pharmaceutical Co., Ltd.), and vitamin mixture (manufactured by Tanabe Seiyaku Co., Ltd.) were mixed and dissolved in warm water, then processed fat (manufactured by Taiyo Yushi Co., Ltd.) was added and homogenized. The raw material composition thus obtained was filled into a container and retort-sterilized at 120°C for 4 minutes or more to prepare a liquid composition with the nutritional composition shown in Table 7.

[0107] Subsequently, the lydinoalanine and copper utilization of the composition were measured. As a result, the amount of lydinoalanine produced was 940 μg per gram of protein, and the copper utilization showed a rate of 70% or more. From the above, it was shown that even if the protein concentration and copper concentration in the nutritional composition differ, similar effects can be obtained by reducing the amount of LAL produced.

[0108] [Table 7]

Claims

1. A nutritional composition, It contains casein as a protein component and a copper-containing additive as copper. The nutritional composition, The protein component contains lysinoalanine in an amount of 3,000 μg or less per gram, The aforementioned copper is contained in an amount of 0.01 mg or more per 100 g of the nutritional composition. The aforementioned nutritional composition.

2. The nutritional composition according to claim 1, wherein the nutritional composition contains the protein component in an amount of 2 g or more per 100 g of the nutritional composition.

3. The nutritional composition according to claim 1 or 2, wherein the viscosity of the nutritional composition at 20°C is 10 mPa·s or more.

4. The nutritional composition according to any one of claims 1 to 3, further comprising a thickening agent.

5. The nutritional composition according to any one of claims 1 to 4, wherein the energy content per gram of the nutritional composition is 0.8 kcal or more.

6. The nutritional composition according to any one of claims 1 to 5, wherein the protein component comprises micellar casein.

7. The nutritional composition according to claim 6, wherein the nutritional composition contains the micellar casein in an amount of 1 g or more per 100 g of the nutritional composition.

8. The nutritional composition according to any one of claims 1 to 5, wherein the protein component comprises a casein hydrolysate or a collagen hydrolysate.

9. A method for producing a nutritional composition, The nutritional composition, It contains casein as a protein component and a copper-containing additive as copper. The nutritional composition, The protein component contains lysinoalanine in an amount of 3,000 μg or less per gram, The aforementioned copper is contained in an amount of 0.01 mg or more per 100 g of the nutritional composition. A preparation step of preparing a mixture containing the protein component and the copper, A sterilization step for sterilizing the mixture, Includes, The sterilization step is carried out such that the time during which the mixture is maintained at 100°C or above is 3 minutes or less. The pH of the mixture is 6.5 or less. The aforementioned manufacturing method.

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