JP7300243B2 - nutritional composition - Google Patents

Description

FIELD OF THE DISCLOSURE The present disclosure relates to nutritional compositions, and more particularly to flowable nutritional compositions.

Various nutritional compositions for administration to patients and the like are known in the prior art. A nutritional composition supplements, for example, nutritional components that are deficient in patients and the like, and contributes to prevention and improvement of diseases.

Japanese National Publication of International Patent Application No. 2013-515718 discloses a nutritional composition used for prevention or treatment of diseases associated with muscle wasting. The nutritional composition contains at least about 12 g of proteinaceous material per 100 kcal. Proteinaceous substances include about 80% whey protein by weight.

The nutritional composition of JP-A-2013-515718 is low in calories and high in protein. According to Japanese National Publication of International Patent Application No. 2013-515718, when dietary protein is provided in a low-calorie composition, amino acids reach the circulating blood more quickly than when dietary protein is provided in a high-calorie composition. , blood levels of amino acids increase. This stimulates muscle protein synthesis.

Patients undergoing rehabilitation (rehabilitation patients) are generally undernourished in many cases. If rehabilitation patients remain malnourished and do not take in adequate nutrition, their physical function cannot be improved and may even deteriorate. Therefore, it is important that rehabilitation patients maintain proper nutritional status (rehabilitation nutrition (rehabilitation nutrition)).

Diseases that require rehabilitation nutrition include chronic obstructive pulmonary disease (COPD), liver failure, rheumatoid arthritis, chronic heart failure, chronic renal failure, leg amputation, femoral neck fracture, diabetes, stroke, cancer, and disuse syndrome. , Parkinson's disease, aspiration pneumonia, and pressure ulcers. These diseases may be accompanied by inflammation. When inflammation occurs, muscle protein catabolism is accelerated, causing a decrease in muscle mass (secondary sarcopenia) and cachexia accompanied by weight loss. In addition, when inflammation persists, appetite decreases, making it difficult to take in sufficient nutrients. Therefore, control of inflammation is necessary along with nutritional therapy for successful rehabilitative nutrition.

A nutritional composition is administered to a rehab patient to properly maintain the rehab patient's nutritional status. At this time, it is preferable that the nutritional composition has a good flavor so that the rehabilitation patient can easily take it continuously. It is also preferred that the nutritional composition has stable physical properties and maintains good flavor during storage. Furthermore, it is preferable that the nutritional composition is in a high calorie (high energy) liquid form so that rehabilitation patients who tend to suffer from anorexia can take in the required nutritional components in small amounts. Conventionally, for such applications, nutritional compositions containing high-concentration lipids and nutritional compositions containing free amino acids as a protein source have been used. However, these nutritional compositions have problems such as poor flavor, difficulty in continuous intake, or diarrhea associated with intake. In addition, in order to promote muscle protein synthesis and suppress catabolism, it is desirable to increase the protein content of the liquid composition. There were some problems that could occur.

An object of the present disclosure is to provide a nutritional composition that has good flavor and stable physical properties, is high in calories, and can control inflammation.

A nutritional composition according to the present disclosure contains a protein source. Protein sources include whey proteins and whey peptides. The ratio of the sum of the weight of whey protein and the weight of whey peptides to the total weight of protein source is 80% or more by weight. The protein energy ratio of the nutritional composition is greater than or equal to 16% and less than 50%. The nutritional composition has a caloric density of 100 kcal/100 ml or greater. The nutritional composition is acidic.

The nutritional composition according to the present disclosure is acidic and thus has a good flavor. That is, the patient can feel the refreshing flavor of the nutritional composition and can take the nutritional composition without resistance.

In the nutritional compositions of the present disclosure, 80% or more by weight of the total protein source is whey protein and whey peptides. Whey proteins and whey peptides are less likely to solidify under acidic conditions than casein. Therefore, in the nutritional composition, the occurrence of precipitation or the like is suppressed or prevented, and physical properties can be stabilized. Whey proteins and whey peptides also have anti-inflammatory effects. Therefore, the nutritional composition can control inflammation in rehabilitation patients and the like.

The nutritional composition according to the present disclosure has a caloric density of 100 kcal/100 ml or more, and is composed of higher calories than general nutritional compositions. Therefore, according to the nutritional composition according to the present disclosure, it is possible to supplement the necessary nutritional components for the patient with a relatively small intake.

In nutritional compositions according to the present disclosure, the ratio of weight of whey protein to weight of whey peptides may be from 5:1 to 1:10.

Whey peptides have high anti-inflammatory properties. However, too much peptide may increase osmotic pressure and cause diarrhea. However, according to the above configuration, the weight ratio of whey protein to whey peptides is in the range of 5:1 to 1:10, so the content of whey peptides does not become too high. Therefore, it is possible to provide a high anti-inflammatory effect while preventing the osmotic pressure of the nutritional composition from increasing and causing diarrhea or the like.

The nutritional composition according to the present disclosure may have a pH of 3 or more and 5 or less.

According to the above configuration, it is possible to make the patient who ingests the nutritional composition feel a preferable sour taste. Therefore, it becomes easier for the patient to continuously ingest the nutritional composition.

A nutritional composition according to the present disclosure may further contain a lipid source. Lipid sources can include n-3 fatty acids.

According to the above configuration, the n-3 fatty acid can suppress inflammation associated with the patient's disease. Therefore, it is possible to prevent increased catabolism of muscle proteins caused by inflammation, and as a result, it is possible to prevent decrease in muscle mass (secondary sarcopenia) and cachexia accompanied by decrease in body weight. It can also prevent anorexia due to persistence of inflammation.

A nutritional composition according to the present disclosure may further contain zinc.

In nutritional compositions according to the present disclosure, the protein source may further comprise leucine.

A nutritional composition according to the present disclosure can be used for rehabilitation nutrition.

The nutritional composition according to the present disclosure can be used for prevention and/or amelioration of chronic obstructive pulmonary disease.

A nutritional composition according to the present disclosure can be used for anti-inflammatory purposes.

According to the present disclosure, a high-calorie nutritional composition having good flavor and stable physical properties can be obtained, and inflammation can be controlled.

1 is a graph showing MCP-1 concentrations in alveolar lavage fluid in Example 1, Comparative Example 1, and Control Example 1. FIG. 1 is a graph showing KC concentrations in alveolar lavage fluid in Example 1, Comparative Example 1, and Control Example 1. FIG. 1 is a graph showing MMP-9 concentrations in alveolar lavage fluid in Example 1, Comparative Example 1, and Control Example 1. FIG. 1 is a graph showing NE concentrations in alveolar lavage fluid in Example 1, Comparative Example 1, and Control Example 1. FIG. 1 is a graph showing neutrophil counts in alveolar lavage fluid in Example 1, Comparative Example 1, and Control Example 1. FIG. 2 is a graph showing the KC concentration of alveolar lavage fluid in Examples 2-1 to 2-3, Comparative Example 2, and Control Example 2. FIG. 2 is a graph showing MMP-9 concentrations in alveolar lavage fluid in Examples 2-1 to 2-3, Comparative Example 2, and Control Example 2. FIG. 2 is a graph showing neutrophil counts in alveolar lavage fluid in Examples 2-1 to 2-3, Comparative Example 2, and Control Example 2. FIG. 10 is a graph showing plasma AST activity 24 hours after administration of ConA to the tail vein of mice in Example 3 and Comparative Example 3. FIG. 10 is a graph showing plasma ALT activity 24 hours after administration of ConA to the tail vein of mice in Example 3 and Comparative Example 3. FIG. 2 is a graph showing plasma TNF-α concentrations 2 hours and 4 hours after administration of ConA to the tail vein of mice in Example 3 and Comparative Example 3. FIG. 4 is a graph showing plasma IL-6 concentrations 2 hours and 4 hours after administration of ConA to the tail vein of mice in Example 3 and Comparative Example 3. FIG. 4 is a graph showing plasma MCP-1 concentrations 2 hours and 4 hours after administration of ConA to the tail vein of mice in Example 3 and Comparative Example 3. FIG. 10 is a graph showing plasma AST activity 24 hours after administration of ConA to the tail vein of mice in Examples 4-1 to 4-2 and Comparative Example 4. FIG. 10 is a graph showing plasma ALT activity 24 hours after administration of ConA to the tail vein of mice in Examples 4-1 to 4-2 and Comparative Example 4. FIG. 2 is a graph showing plasma TNF-α concentrations 2 hours and 4 hours after administration of ConA to the tail vein of mice in Examples 4-1 to 4-2 and Comparative Example 4. FIG. 2 is a graph showing plasma IL-6 concentrations 2 hours and 4 hours after administration of ConA to the tail vein of mice in Examples 4-1 to 4-2 and Comparative Example 4. FIG.

For example, patients undergoing rehabilitation (rehabilitation patients) are generally undernourished in many cases. If rehabilitation patients do not take in adequate nutrition, they may not be able to improve their physical function, and their physical function may deteriorate. Therefore, it is important to pay attention to the nutritional status of patients who are likely to be malnourished, such as rehabilitation patients, and to appropriately maintain the nutritional status.

Diseases for which nutritional status should be noted include, for example, chronic obstructive pulmonary disease (COPD), liver failure, rheumatoid arthritis, chronic heart failure, chronic renal failure, lower limb amputation, femoral neck fracture, diabetes, stroke, cancer, and disability. syndrome, Parkinson's disease, aspiration pneumonia, pressure ulcers, and the like. These diseases can be accompanied by inflammation. When inflammation occurs, the catabolism of muscle proteins is accelerated, causing a decrease in muscle mass (secondary sarcopenia) and cachexia accompanied by a decrease in body weight. In addition, when inflammation persists, appetite decreases, making it difficult to take in sufficient nutrients.

[Configuration of nutritional composition]
The nutritional composition according to the present embodiment is used to appropriately maintain a patient's nutritional status. The nutritional composition according to the present embodiment is mainly used for rehabilitation nutrition or support for rehabilitation nutrition. That is, this nutritional composition can be used for rehabilitation patients and contribute to prevention and/or improvement of malnutrition. The nutritional composition can be administered to patients who are to maintain adequate nutritional status, such as patients with the diseases mentioned above. This nutritional composition is used, for example, for the prevention and/or amelioration of chronic obstructive pulmonary disease (COPD). The nutritional composition is also used to promote muscle protein synthesis and inhibit muscle protein breakdown. This nutritional composition may also contribute to the suppression of inflammation. The composition of this nutritional composition will be described below.

The nutritional composition according to this embodiment is fluid. This nutritional composition is, for example, liquid. This nutritional composition has an acidic character. In this nutritional composition, the pH is preferably 3-5.

If the nutritional composition according to the present embodiment has a pH of 3 to 5, the patient who ingests the nutritional composition can feel a moderate sour taste. Therefore, the patient can easily take this nutritional composition continuously, and the nutritional state of the patient can be appropriately maintained.

The nutritional composition according to this embodiment is relatively high in calories. That is, the nutritional composition preferably has a caloric density of 100 kcal/100 ml or more, more preferably 125 kcal/100 ml or more, even more preferably 150 kcal/100 ml or more.

The nutritional composition according to this embodiment contains a protein source and a lipid source. The nutritional composition may preferably contain a protein source at 2-8 g/100 kcal, more preferably a protein source at 3-6/100 kcal, even more preferably 4-6 g/100 kcal. The nutritional composition preferably contains 1-4 g/100 kcal of lipid source, more preferably 2-3.5 g/100 kcal of lipid source, even more preferably 2-3 g/100 kcal of lipid source. be able to. With the amount of protein source and lipid source as described above, the calorie content is high (the calorie density is high), and the physical properties after storage are better.

In the nutritional composition according to this embodiment, the protein source contributes to promotion of muscle protein synthesis. This protein source includes whey protein and whey peptides. In this nutritional composition, the ratio of the sum of the weight of whey protein and the weight of whey peptides to the total weight of the protein source is preferably 80% by weight or more, more preferably 90% by weight or more. In this nutritional composition, the ratio of the weight of whey protein to the weight of whey peptides is preferably from 5:1 to 1:10, more preferably from 3:1 to 1:7.

The nutritional composition according to the present embodiment contains whey peptides that increase the osmotic pressure in the nutritional composition by setting the weight ratio of whey protein to whey peptides in the range of 5:1 to 1:10. It is possible to prevent the amount from becoming too large. Therefore, in this nutritional composition, an increase in osmotic pressure can be prevented, and an anti-inflammatory action can be imparted while preventing diarrhea and the like from occurring.

The whey according to the present embodiment is, for example, water-soluble components remaining when fat, casein, fat-soluble vitamins, etc. are removed from milk. Whey is generally produced by producing cheese whey and rennet whey (also known as sweet whey) as a by-product of the production of natural cheese and rennet casein, acid casein, fermented milk and quark from skimmed milk. casein whey, acid whey, and quark whey. Whey protein is a generic term for proteins other than casein, such as in milk. Whey protein is composed of multiple components such as β-lactoglobulin, α-lactalbumin, and lactoferrin, and does not contain lactose, vitamins, minerals, and the like. When a dairy raw material such as milk is acidified, the protein that precipitates is casein, and the protein that does not precipitate is whey protein.

In addition, the whey according to the present embodiment includes concentrated whey obtained by concentrating whey, whey powder obtained by drying whey, and the main protein of whey by ultrafiltration (UF) method etc. After concentration treatment, it is dried. Processed whey protein concentrate (hereinafter also referred to as "WPC"), whey is subjected to microfiltration (MF) method, centrifugation method, etc. to remove fat, then concentrated by UF method and then dried Treated defatted WPC (low-fat, high-protein), whey protein isolate (Whey Protein Isolate: hereinafter , Also referred to as "WPI"), desalted whey that has been desalted by nanofiltration (NF) method or electrodialysis method and then dried, whey-derived mineral components are precipitated and then centrifuged. Concentrated mineral-concentrated whey and the like are also included.

The whey peptide according to the present embodiment can be produced, for example, by hydrolyzing whey or whey protein with the following enzymes. Enzymes used for hydrolysis of whey are pepsin, trypsin and chymotrypsin. Research reports using papain derived from plants and proteases derived from bacteria and fungi (Food Technol., 48: 68-71, 1994; Trends Food Sci. Technol., 7:120-125, 1996; Food Proteins and Their Applications, pp. 443-472, 1997). Enzyme activities that hydrolyze whey proteins vary widely. Pepsin degrades α-La and denatured α-La, but not native β-Lg (Neth. Milk dairy J., 47:15-22, 1993). Trypsin slowly hydrolyzes α-La while β-Lg remains largely undegraded (Neth. Milk dairy J., 45:225-240, 1991). Chymotrypsin degrades α-La fast, but β-Lg is slowly degraded. Papain hydrolyzes bovine serum albumin (BSA) and β-Lg, whereas α-La is resistant (Int. Dairy Journal 6:13-31, 1996a). However, α-La with no bound Ca is completely degraded by papain at acidic pH (J. Dairy Sci., 76:311-320, 1993).

Hydrolysis of peptide bonds results in an increase in the number and hydrophobicity of charged groups, a reduction in molecular weight, and a modification of the conformation of the molecule (J. Dairy Sci., 76:311-320, 1993). Changes in functional properties are highly dependent on the degree of hydrolysis. The most common changes in whey protein functionality are increased solubility and decreased viscosity. When the degree of hydrolysis is high, often the hydrolyzate does not precipitate on heating and is highly soluble at pH 3.5-4.2. Hydrolysates are also much less viscous than intact proteins. This difference is particularly pronounced when the protein concentration is high. Other effects are changes in gel properties, increased thermal stability, increased emulsification and foaming properties, decreased emulsification and foam stability.

The whey peptides used in this embodiment preferably have anti-inflammatory effects. For example, the effect of suppressing LPS-induced TNF-α and IL-6 production in vivo is confirmed. Whether or not it has the effect of suppressing LPS-induced TNF-α and IL-6 production can be determined using a known assay system (e.g., Jikken Igaku Supplement, "Biomanual UP Experimental Series", Cytokine Experimental Method, Atsushi Miyajima, Masaru Yamamoto eds. , Yodosha Co., Ltd., 1997). Optimization of whey protein hydrolysis conditions (denaturation temperature, pH, temperature, hydrolysis time and enzyme/substrate ratio) using the inhibitory effect of LPS-induced TNF-α and/or IL-6 production as an index is described in the above literature ( International Dairy Journal 12:813-820, 2002). The whey peptides used in the present embodiment include the whey peptides themselves, the retentate after ultrafiltration membrane treatment, or the permeate (permeate).

Examples of whey protein hydrolysates that can be used in the present embodiment include the following. Japanese Patent No. 3183945 is obtained by hydrolyzing a heat-denatured whey protein isolate (WPI) with endopeptidase and exopeptidase, and then adsorbing aromatic amino acids in this hydrolyzate with an ion exchange resin. , disclose whey protein hydrolysates (mixtures of peptides with molecular weights of 200-3,000) having a Fischer ratio of 10 or greater, 15% or greater branched chain amino acids, and less than 2% aromatic amino acids.

Japanese Patent Publication No. 6-50756 describes a 12% aqueous solution of whey protein concentrate (WPC) having a protein content of at least 65%, after heat treatment at a temperature exceeding 60°C, B. alcalase from licheniformis and B. Hydrolyzed with Neutrase from subtilis to 15-35% DH, this hydrolyzate was subjected to Ultrafiltration (UF) with a cut-off value greater than 10,000 followed by Nanofiltration (NF). and spray-drying this NF retentate to obtain odorless, less bitter whey peptides.

Examples of commercially available milk protein hydrolysates used in the present embodiment include Peptigen IF-3080, Peptigen IF-3090, Peptigen IF-3091 and Lacprodan DI-3065 (Arla Foods), WE80BG (DMV) , Hyprol 3301, Hyprol 8361 and Hyprol 8034 (Kerry), Tatua 2016, HMP406 (Tatua), Why Hydrolysate 7050 (Fonterra), Biozate 3 (Davisco), and the like. Methods for preparing protein hydrolysates include, for example, methods for producing whey peptides, including the following steps 1) to 5).

1) mixing whey protein containing at least 65% protein, calculated as dry matter, with water to form a slurry with a protein content of up to 20%;
2) heat treatment up to a temperature above 60°C,
3) The mixture from step 2) is subjected to a non-pH - proteolytically hydrolyzed to between 15 and 35% DH by the Stat method,
4) Separating the mixture from step 3) on an ultrafiltration/microfiltration device with a cut-off value greater than 10,000 such that the permeate constitutes protein hydrolysates (whey peptides). and 5) the hydrolysis is terminated by inactivation of the enzyme.

Preferably, the slurry in step 1) above has a protein content of 7-12%. Preferably, the heat treatment in step 2) above is performed between 70 and 90°C. Preferably, the hydrolysis in step 3) above is performed to a DH between 20-30%. Preferably, the cut-off value of said ultrafiltration/microfiltration device is above 50,000.

Preferably, the mixture at the end of step 3) or step 5) above, in an amount corresponding to between 1 and 5% carbon, calculated on the dry matter content, preferably at a temperature between 50 and 70° C. , is treated with activated charcoal for more than 5 minutes and the activated charcoal is removed. Preferably, after step 5) above, concentration is carried out by nanofiltration/hyperfiltration/reverse osmosis and/or evaporation, preferably at a temperature between 50 and 70° C., followed by retention thereof. The product is recovered as its protein hydrolyzate (whey peptide) solution.

Preferably, the protein hydrolyzate (whey peptide) solution from step 5) above is spray dried to a moisture content of less than 6.5%.

Accordingly, a method for the production of whey protein hydrolysates comprises
1) mixing whey protein containing at least 65% protein, calculated as dry matter, with water to form a slurry having a protein content of up to about 20%, preferably up to 12%;
2) heat treatment up to a temperature above 60°C,
3) making the mixture from step 2) with a protease that can be made by B. licheniformis, preferably Alcalase® and/or by B. subtilis proteolytic hydrolysis by a non-pH-stat method to a DH between 15 and 35% by a protease, preferably Neutrase®, capable of
4) separating the mixture from step 3) on an ultrafiltration/microfiltration device with a cut-off value greater than 10,000 so that the permeate constitutes the protein hydrolysate, and ,
5) terminating the hydrolysis by inactivation of the enzyme;
characterized by

In the nutritional composition according to this embodiment, the protein source can contain proteins other than whey protein, peptides other than whey peptides, and/or amino acids. In this nutritional composition, the protein source may contain, for example, leucine. The nutritional composition preferably contains 0.01-1.0 g/100 kcal of leucine, more preferably 0.05-0.5 g/100 kcal of leucine.

In the nutritional composition according to this embodiment, the protein source is substantially free of casein. Casein is easier to solidify than whey proteins and whey peptides. Casein tends to solidify, especially under acidic conditions. In this nutritional composition, the protein source substantially does not contain casein, so that precipitation or the like is suppressed or prevented in the nutritional composition, and physical properties can be stabilized.

In the nutritional composition according to this embodiment, the protein energy ratio is preferably 16% or more and less than 50%, more preferably 20% or more and less than 30%. That is, the nutritional composition is high in protein and promotes muscle protein synthesis in the patient's body.

In the nutritional composition according to this embodiment, the lipid source contains n-3 fatty acids. The nutritional composition preferably contains 10-100 mg/100 kcal of n-3 fatty acid, and more preferably 30-80 mg/100 kcal of n-3 fatty acid.

In the nutritional composition according to this embodiment, the n-3 fatty acid preferably contains eicosapentaenoic acid (EPA) and/or docosahexaenoic acid (DHA). EPA and DHA have anti-inflammatory effects. In the nutritional composition according to the present embodiment, when the n-3 fatty acid contains EPA, it preferably contains EPA at 1 to 100 mg/100 kcal, more preferably from the viewpoint of the flavor of the nutritional composition. , EPA can be contained at 10-30 mg/100 kcal. In this nutritional composition, when the n-3 fatty acid contains DHA, from the viewpoint of the flavor of this nutritional composition, it preferably contains 1 to 100 mg/100 kcal of DHA, more preferably 10 mg/100 kcal of DHA. It can be contained at ~50 mg/100 kcal.

Fish oil may be used as at least a portion of the lipid source in the nutritional composition according to this embodiment. Fish oil is rich in EPA and DHA. In this nutritional composition, when fish oil is used as a lipid source, this nutritional composition preferably contains 0.05 to 0.5 g/100 kcal of fish oil, and more preferably 0 from the viewpoint of flavor. .1 to 0.3 g/100 kcal.

When inflammation occurs, muscle protein catabolism is accelerated, causing a decrease in muscle mass (secondary sarcopenia) and cachexia accompanied by a decrease in body weight. Also, persistent inflammation reduces the patient's appetite. However, in the nutritional composition according to this embodiment, if the lipid source contains n-3 fatty acids, especially EPA and/or DHA, inflammation associated with the patient's disease can be suppressed. Therefore, the above harmful effects caused by inflammation can be reduced.

In the nutritional composition according to this embodiment, the lipid source may contain medium-chain fatty acid triglycerides. Medium-chain fatty acid triglycerides are digested and absorbed more quickly than long-chain fatty acid triglycerides. The nutritional composition preferably contains 0.2 to 2.0 g/100 kcal of medium chain fatty acid triglyceride, more preferably 0.4 to 0.8 g/100 kcal of medium chain fatty acid triglyceride. can.

The nutritional composition according to this embodiment preferably contains vitamin C and/or vitamin E. Vitamin C and vitamin E have antioxidant properties. The nutritional composition preferably contains 1 to 1000 mg/100 kcal of vitamin C, and more preferably 10 to 100 mg/100 kcal of vitamin C. The nutritional composition preferably contains 0.1 to 100 mg/100 kcal of vitamin E, and more preferably 1 to 10 mg/100 kcal of vitamin E.

The nutritional composition according to this embodiment can contain vitamins other than vitamin C and vitamin E. This nutritional composition can contain, for example, one or more of vitamin B ₁ , vitamin B ₂ , vitamin B ₆ , vitamin B ₁₂ , niacin, pantothenic acid, folic acid, and the like.

The nutritional composition according to this embodiment preferably contains zinc. Zinc has an anti-inflammatory action and an action that enhances muscle synthesis. The nutritional composition preferably contains zinc at 0.1-10 mg/100 kcal, and more preferably may contain zinc at 0.5-5 mg/100 kcal.

The nutritional composition according to this embodiment can contain minerals other than zinc. The nutritional composition can contain, for example, one or more of potassium, sodium, calcium, magnesium, iron, and the like.

In the nutritional composition according to this embodiment, the content of potassium is preferably 20-500 mg/100 kcal, more preferably 20-300 mg/100 kcal. The sodium content is preferably 20-500 mg/100 kcal, more preferably 20-300 mg/100 kcal. The content of calcium is preferably 20-300 mg/100 kcal, more preferably 20-250 mg/100 kcal, even more preferably 20-150 mg/100 kcal. The content of magnesium is 5-300 mg/100 kcal, more preferably 10-200 mg/100 kcal, still more preferably 10-100 mg/100 kcal. By setting the content of each mineral within the above range, it is possible to replenish an appropriate amount of minerals for a rehabilitation patient or the like. In addition, it is possible to improve suitability (dispersion) during production of the nutritional composition according to the present embodiment, and to suppress sedimentation of the fluid nutritional composition during storage.

The nutritional composition according to this embodiment may contain ingredients other than those mentioned above. This nutritional composition can contain components at necessary concentrations according to the patient's disease, nutritional status, and the like.

The nutritional composition according to this embodiment may contain carbohydrates such as sugars and dietary fiber. The nutritional composition can contain palatinose and/or dextrin as carbohydrates, for example. The content of carbohydrates such as palatinose and/or dextrin is preferably 10-16 g/100 kcal, more preferably 12-14 g/100 kcal. Many patients with diseases requiring rehabilitation nutrition also have diabetes. Therefore, in the nutritional composition according to the present embodiment, it is preferable to use 20% by weight or more of palatinose, which absorbs sugar slowly, based on the total sugar content. More preferably, the amount of palatinose used is 50% by weight or more of the total carbohydrates.

In the nutritional composition according to the present embodiment, as the dietary fiber, it is preferable to use indigestible dextrin, which has the effect of suppressing postprandial blood sugar elevation and is less likely to cause excessive viscosity during production. The content of dietary fiber such as indigestible dextrin is preferably 0.5-3.0 g/100 kcal, more preferably 1.0-2.0 g/100 kcal.

[Method for producing nutritional composition]
Next, an example of a method for producing the nutritional composition according to this embodiment will be described. However, the method for producing this nutritional composition is not limited to the production method described below.

First, the ingredients of the nutritional composition are prepared. Specifically, 22,000 g of dissolving water is added (thrown in) to a mixing tank (mixer). This dissolved water is, for example, tap water, purified water, ion-exchanged water, RO water from which impurities have been removed by a reverse osmosis (RO) membrane, or the like. The temperature of this dissolved water can be set to about 40 to 80.degree. Then, dextrin (75% by weight dextrin solution): 169 g is added to the preparation tank, and the dissolved water and dextrin are mixed (stirred).

Next, ferrous sulfate: 0.08 g and pH adjuster: 26 g are added to the mixing tank and mixed, and then oil and fat adjustment liquid: 2,328 g (for example, vegetable oil: 2,200 g, animal oil and fat: 128 g, etc.) and mix. Furthermore, whey peptide (whey protein hydrolyzate): 2,640 g, whey protein concentrate: 3,000 g, dietary fiber: 750 g, palatinose: 3,360 g, emulsifier: 780 g, branched chain amino acid: 240 g, stabilizer: 3, After adding 360 g and mixing, add calcium preparation: 630 g, magnesium phosphate: 90 g, selenium yeast: 2 g, zinc gluconate: 7 g, copper gluconate: 0.36 g, salt: 96 g, potassium chloride: 42 g to mix.

The pH adjuster is not particularly limited as long as it can be used for food, and organic acids and inorganic acids can be used alone or in combination of two or more as the pH adjuster. Examples of organic acids that can be used include lactic acid, malic acid, citric acid, succinic acid, tartaric acid, ascorbic acid, gluconic acid, fumaric acid and salts thereof. Examples of inorganic acids that can be used include hydrochloric acid, phosphoric acid and salts thereof. Food additives can be used as the organic acid, but naturally occurring organic acids such as lemon juice and apple juice can also be used. The oil-and-fat adjustment liquid is not particularly limited as long as it can be used for food. More than one species can be mixed and used. The temperature of the oil-and-fat adjustment liquid can be set to about 50 to 60°C.

While mixing (stirring) the above-described components in a mixing tank, the mixture is maintained at, for example, 50 to 60° C. for 15 minutes or more (15 to 60 minutes). This completes the formulation of the ingredients of the nutritional composition.

Next, the preparation liquid (raw material) prepared in the preparation tank is preheated and heat sterilized. In the preheating treatment, for example, a plate heat exchanger, tube heat exchanger, or the like is used to heat the prepared liquid to 75 to 85°C. In the heat sterilization treatment, for example, a plate heat exchanger, a tube heat exchanger, a steam injection heater, a steam infusion heater, etc. are used, and the prepared solution after the preliminary heat treatment is heated to, for example, 120 to 145 ° C., 1 Heat for ~10 seconds.

Next, the heat sterilized liquid preparation is pre-cooled and pre-homogenized. In the pre-cooling treatment, for example, a plate heat exchanger, tube heat exchanger, or the like is used to cool the prepared liquid to 70 to 80°C. In the preliminary homogenization treatment, for example, a homogenizer is used to homogenize (miniaturize) the prepared liquid at, for example, 70 to 80° C. and 40 to 60 MPa. Then, for example, using a plate-type heat exchanger, a tube-type heat exchanger, etc., the pre-homogenized prepared liquid is cooled to, for example, 5 to 25° C. and stored in an intermediate liquid storage tank.

While mixing (stirring) the prepared liquid in the intermediate liquid storage tank, it is maintained at, for example, 5 to 25°C. Vitamins (for example, vitamin C: 87 g, vitamin E: 9 g, etc.) are added and mixed in the intermediate liquid storage tank in which the prepared liquid is stored. Then, 258 g of flavor and 18 g of sweetener are added to the intermediate liquid storage tank and mixed.

Next, the prepared liquid to which vitamins and the like have been added is subjected to preliminary heating treatment and main homogenization treatment. In the preheating treatment, for example, a plate heat exchanger, tube heat exchanger, or the like is used to heat the prepared liquid to 70 to 80°C. In this homogenization treatment, for example, a homogenizer is used to homogenize (miniaturize) the prepared liquid after the preliminary heat treatment at, for example, 70 to 80° C. and 40 to 60 MPa. Then, for example, using a plate heat exchanger, a tube heat exchanger, etc., the homogenized prepared liquid is cooled to, for example, 5 to 25° C. and stored in a final liquid storage tank.

While mixing (stirring) the prepared liquid (nutritional composition, intermediate product) in the final liquid storage tank, it is held at, for example, 5 to 25°C. A suitable container is filled with the prepared liquid from the final liquid storage tank in which the prepared liquid is stored. This completes the nutritional composition (final product) according to the present embodiment.

[effect]
Since the nutritional composition according to the present embodiment is acidic, it has a refreshing and favorable flavor. That is, the patient or the like can feel the refreshing and good flavor of the nutritional composition, and can take the nutritional composition without hesitation. Therefore, for example, it becomes easier for a rehabilitation patient or the like who is likely to be in a state of malnutrition to continuously ingest the nutritional composition, and it is possible to appropriately maintain the nutritional state of the rehabilitation patient or the like.

In the nutritional composition according to this embodiment, 80% or more by weight of the total weight of the protein source is whey protein and whey peptides. Whey proteins and whey peptides are less likely to solidify under acidic conditions than casein. Therefore, in the nutritional composition, the occurrence of precipitation or the like is suppressed or prevented, and physical properties can be stabilized.

The nutritional composition according to the present embodiment has a calorie density of 100 kcal/100 ml or more, and has a higher calorie content than general nutritional compositions. Therefore, even if the patient or the like ingests only a small amount of the nutritional composition, it is possible to appropriately maintain the nutritional state of the patient or the like. Then, it becomes possible to effectively improve the nutritional status of patients with anorexia and the like.

Since the nutritional composition according to the present embodiment is high in calories, it is possible to suppress the use of the protein source contained in the nutritional composition as an energy source in the body of a patient or the like. Therefore, the protein source can more reliably contribute to the synthesis of muscle protein, and the decomposition of muscle protein can be suppressed. Therefore, for example, if the nutritional composition according to the present embodiment is used for rehabilitation patients or the like, rehabilitation can be effectively performed. At this time, the QOL (Quality Of Life) of the rehabilitation patient is improved, and it can be expected to prevent an increase in nursing care and a deterioration in the level of nursing care required.

Although the embodiments have been described above, the present disclosure is not limited to the above embodiments, and various modifications are possible without departing from the gist thereof.

Each example will be described below. However, the present disclosure is not limited to the following examples.

[Experiment 1. Evaluation test of a nutritional composition using an animal model of chronic obstructive pulmonary disease (COPD)]
(Method for producing a model animal of COPD)
Twenty-four C57BL/6J strain male mice (3 weeks old) were used. Mice were acclimatized by feeding a general diet (standard purified diet (AIN93G)) for 7 days (1 week), divided into 3 groups based on body weight, and fed a test diet for 14 days (2 weeks). and reared.

Tobacco smoke exposure group (Smoke)
After the mice were fed the test diet for 14 days (2 weeks) and housed, the mice were exposed to tobacco smoke continuously for 10 days. Mice were also fed test diets during periods of tobacco smoke exposure. The method of exposure to tobacco smoke is as follows.

Mice were placed in the chamber for exposure, and cigarettes (pieces, manufactured by Japan Tobacco Inc., tar: 28 mg/ Mainstream smoke (tobacco smoke: air = 1:5, flow rate: 1.05L/min) was generated, and the mainstream tobacco smoke was fed into the chamber. At this time, the mice were exposed to 20 cigarettes for about 1.5 hours per day.

Non-tobacco smoke exposure group (air exposure group) (Air)
After the mice were fed and housed with the test diet for 14 days (2 weeks), the mice were continuously exposed to air for 10 days. The test diet was also fed during the period of air exposure to the mice. As for the air exposure method, mice were placed in an air exposure chamber, and air was sent into the chamber using an air pump.

(Test method)
Example 1
A mixture (Nutrition composition: liquid diet = 70:30 (weight ratio)) was continuously given ad libitum for 24 days (breeding period: 14 days and tobacco smoke exposure period: 10 days). Table 1 shows the composition of the nutritional composition used in Example 1.

The pH of the nutritional composition shown in Table 1 is 4.1. The caloric density of this nutritional composition is 160 kcal/100 ml. The protein energy ratio of this nutritional composition is 20%. The protein source of this nutritional composition includes 2.5 g/100 kcal whey protein and 2.3 g/100 kcal whey peptides. The ratio of the combined weight of whey protein and whey peptides to the total weight of protein source of this nutritional composition is 96% by weight. EPA is 0.10 g/100 kcal. DHA is 0.04 g/100 kcal.

Comparative example 1
Eight mice in the cigarette smoke exposure group were given a freeze-dried powder of a general liquid diet (Meibalance HP, manufactured by Meiji Co., Ltd.) as a test feed for 24 days (breeding period: 14 days, and cigarette smoke exposure period: 10 days). The mice were given ad libitum ingestion continuously for 2 days).

Control example 1
Eight mice in the non-tobacco smoke exposure group were given a freeze-dried powder of a general liquid diet (Meibalance HP, manufactured by Meiji Co., Ltd.) as a test feed for 24 days (breeding period: 14 days, and air exposure period: 10 days). The mice were given ad libitum ingestion continuously for 2 days).

(evaluation)
As indicators of alveolar inflammation, monocyte chemoattractant protein-1 (MCP-1) concentration, neutrophil chemokine Keratinocyte-derived chemokine (KC) concentration, matrix metalloproteinase 9 (Matrix metalloproteinase 9 (MMP-9)) concentration, neutrophil elastase (NE) concentration, and neutrophil count were used. Here, the measured value of each index was evaluated by means±standard error. In statistical analysis, Dunnett's test or Steel's test was used with Comparative Example 1 as a control group.

In Comparative Example 1, when the measured value of each index is higher than in Control Example 1, inflammation is induced in Comparative Example 1. On the other hand, in Example 1, when the measured value of each index is lower than in Comparative Example 1, it means that inflammation is suppressed in Example 1.

For each index measurement, each mouse was exsanguinated and exsanguinated 24 hours after cigarette smoke or air exposure ended. Here, the alveoli were washed with PBS three times (1 mL each) and the alveolar lavage fluid was collected. For measurement of MCP-1 concentration, KC concentration, MMP-9 concentration, and NE concentration, the collected alveolar lavage fluid was centrifuged, and the supernatant of this alveolar lavage fluid was used. On the other hand, for the measurement of the neutrophil count, the alveolar lavage fluid precipitate was suspended in PBS, and a suspension of the lavage fluid precipitate was used.

A Cytometric Bead Array (CBA) Mouse Inflammation kit manufactured by Nippon Becton Dickinson Co., Ltd. was used to measure the MCP-1 concentration. Mouse KC Quantikine ELISA Kit manufactured by R&D was used to measure the KC concentration. Mouse Total MMP-9 Quantikine ELISA Kit manufactured by R&D was used to measure MMP-9 concentration. A Neutrophil Elastase ELISA Kit manufactured by Cusabio was used to measure the NE concentration.

The MCP-1 concentrations in alveolar lavage fluid in Example 1, Comparative Example 1, and Control Example 1 are shown in FIG. As can be seen from FIG. 1, in Comparative Example 1, the MCP-1 concentration was significantly higher than in Control Example 1. In Example 1, the MCP-1 concentration was significantly lower than in Comparative Example 1.

The KC concentration of the alveolar lavage fluid in Example 1, Comparative Example 1, and Control Example 1 is shown in FIG. As can be seen from FIG. 2, in Comparative Example 1, the KC concentration was significantly higher than in Control Example 1. In Example 1, the KC concentration tended to be lower than in Comparative Example 1.

The MMP-9 concentrations in alveolar lavage fluid in Example 1, Comparative Example 1, and Control Example 1 are shown in FIG. As can be seen from FIG. 3, MMP-9 concentration was significantly higher in Comparative Example 1 than in Control Example 1. In Example 1, the MMP-9 concentration was significantly lower than in Comparative Example 1.

The NE concentration of the alveolar lavage fluid in Example 1, Comparative Example 1, and Control Example 1 is shown in FIG. As can be seen from FIG. 4, in Comparative Example 1, the NE concentration was significantly higher than in Control Example 1. In Example 1, the NE concentration was significantly lower than in Comparative Example 1.

The neutrophil count in the alveolar lavage fluid in Example 1, Comparative Example 1, and Control Example 1 is shown in FIG. As can be seen from FIG. 5, in Comparative Example 1, the neutrophil count was significantly higher than in Control Example 1. In Example 1, the neutrophil count was significantly lower than in Comparative Example 1.

(Discussion)
In Comparative Example 1, the measured values of each index were higher than those in Control Example 1. This indicates that exposure to tobacco smoke induces inflammation. On the other hand, in Example 1, compared with Comparative Example 1, the measured values of each index were low. That is, when mice ingested the nutritional composition shown in Table 1, each index value showed a low value even though the mice were exposed to tobacco smoke. From this, it can be seen that the nutritional composition according to the present disclosure reduces the concentration of various inflammatory mediators induced by COPD and suppresses the increase in inflammatory cells (neutrophil count). Furthermore, it can be seen that the nutritional composition according to the present disclosure suppresses secretion of various enzymes that cause damage to alveolar tissue. That is, it was confirmed that the nutritional composition according to the present disclosure has an anti-inflammatory (anti-inflammatory) effect.

[Experiment 2. Evaluation test of whey protein, whey peptide, fish oil using animal model of chronic obstructive pulmonary disease (COPD)]
(Method for producing a model animal of COPD)
Thirty C57BL/6J strain female mice (6 weeks old) were used. Mice were acclimatized by feeding a general diet (standard purified diet (AIN93G)) for 7 days (1 week), divided into 4 groups based on body weight, and fed a test diet for 14 days (2 weeks). and reared.

Tobacco smoke exposure group (Smoke)
After the mice were fed the test diet for 14 days (2 weeks) and housed, the mice were exposed to cigarette smoke for 3 consecutive days. Mice were also fed test diets during periods of tobacco smoke exposure. The method of exposure to tobacco smoke is as follows.

Mice of the cigarette smoke exposure group (Smoke) were placed in the chamber for exposure, and tobacco (piece, manufactured by Japan Tobacco Inc., tar: 28 mg/piece, nicotine: 2.3 mg/piece) was introduced using a peristaltic pump. of tobacco smoke (tobacco smoke:air=1:5, flow rate: 600 mL/min) was generated, and the mainstream tobacco smoke was fed into the chamber. At this time, the mice were exposed to tobacco smoke for 3 hours on the first day and for 4 hours on the second and third days.

Non-tobacco smoke exposure group (air exposure group) (Air)
After the mice were fed and housed with the test diet for 14 days (2 weeks), the mice were exposed to air for 3 consecutive days. The test diet was also fed during the period of air exposure to the mice. As for the air exposure method, mice were placed in an air exposure chamber, and air was sent into the chamber using an air pump.

(Test method)
Example 2-1
A whey diet was prepared by substituting the entire protein source of the standard purified feed (AIN93G) with whey protein and whey peptide (whey protein:whey peptide=1:1 (weight ratio)). Six mice in the tobacco smoke exposure group were allowed to freely ingest the whey diet as the test feed continuously for 17 days (the breeding period after switching to the whey diet: 14 days, and the tobacco smoke exposure period: 3 days). rice field.

Example 2-2
A fish oil diet was prepared by substituting half the lipid source (50% by weight) of the standard refined diet (AIN93G) with fish oil. Six mice in the tobacco smoke exposure group were allowed to freely ingest a fish oil diet as a test feed for 17 days (raising period after switching to fish oil diet: 14 days, and tobacco smoke exposure period: 3 days). rice field.

Example 2-3
Replace the entire amount of the protein source of the standard refined feed (AIN93G) with whey protein and whey peptide (whey protein: whey peptide = 1: 1 (weight ratio)), and half the lipid source (50% by weight) to fish oil Instead, a whey/fish oil diet was prepared. Six mice in the cigarette smoke exposure group were fed whey/fish oil diet as a test feed for 17 days (breeding period after switching to whey/fish oil diet: 14 days, and tobacco smoke exposure period: 3 days) continuously. were given ad libitum.

Comparative example 2
6 mice in the tobacco smoke exposure group were continuously fed a standard purified diet (AIN93G) as a test diet for 17 days (standard refined diet feeding period: 14 days, and tobacco smoke exposure period: 3 days). let me

Control example 2
6 mice in the non-tobacco smoke exposure group were continuously given a standard purified diet (AIN93G) as a test diet for 17 days (standard refined diet feeding period: 14 days, and air exposure period: 3 days). let me

(evaluation)
Neutrophil chemokine (KC) levels, matrix metalloproteinase 9 (MMP-9) levels, and neutrophil counts were used as indicators of alveolar inflammation. Here, the measured value of each index was evaluated by means±standard error. In statistical analysis, Dunnett's test or Steel's test was used with Comparative Example 2 as a control group.

In Comparative Example 2, when the measured value of each index is higher than in Control Example 2, inflammation is induced in Comparative Example 2. On the other hand, in Examples 2-1 to 2-3, when the measured values of each index were lower than in Comparative Example 2, inflammation was suppressed in Examples 2-1 to 2-3. becomes. The same method as in Experiment 1 was used to measure each index.

FIG. 6 shows the KC concentration of the alveolar lavage fluid in Examples 2-1 to 2-3, Comparative Example 2, and Control Example 2. As can be seen from FIG. 6, in Comparative Example 2, the KC concentration was significantly higher than in Control Example 2. In Example 2-1, the KC concentration tended to be lower than in Comparative Example 2. In Example 2-2, the KC concentration was significantly lower than in Comparative Example 2. In Example 2-3, the KC concentration tended to be lower than in Comparative Example 2. Also, in Example 2-3, the KC concentration was about the same value as in Example 2-2.

FIG. 7 shows the MMP-9 concentrations in alveolar lavage fluid in Examples 2-1 to 2-3, Comparative Example 2, and Control Example 2. As can be seen from FIG. 7, the MMP-9 concentration was significantly higher in Comparative Example 2 than in Control Example 2. In Example 2-1, MMP-9 concentration tended to be lower than in Comparative Example 2. In Example 2-2, MMP-9 concentration was significantly lower than in Comparative Example 2. In Example 2-3, MMP-9 concentration was significantly lower than in Comparative Example 2.

FIG. 8 shows the neutrophil count in alveolar lavage fluid in Examples 2-1 to 2-3, Comparative Example 2, and Control Example 2. As can be seen from FIG. 8, in Comparative Example 2, the neutrophil count was significantly higher than in Control Example 2. In Example 2-1, the neutrophil count tended to be lower than in Comparative Example 2. In Example 2-2, the neutrophil count was significantly lower than in Comparative Example 2. In Example 2-3, the neutrophil count was significantly lower than in Comparative Example 2.

(Discussion)
In Comparative Example 2, the measured values of each index were higher than those in Control Example 2. This indicates that exposure to tobacco smoke induces inflammation. On the other hand, in Examples 2-1 to 2-3, compared with Comparative Example 2, the measured values of each index were low. That is, when mice ingested a nutritional composition enriched with whey protein and whey peptides and a nutritional composition enriched with fish oil, each index value was low despite exposure to tobacco smoke. . From this, it can be seen that the nutritional composition according to the present disclosure reduces the concentration of neutrophil chemokines induced by COPD and suppresses the increase in inflammatory cells (neutrophil count). Furthermore, it can be seen that the nutritional composition according to the present disclosure inhibits the secretion of enzymes that are released from inflammatory cells and cause tissue damage. In other words, it was confirmed that the nutritional composition, whey protein, whey peptide, and fish oil according to the present disclosure have an inflammation-improving (anti-inflammatory) effect.

[Experiment 3. Evaluation test of nutritional composition using hepatitis model animal (1)]
(Method for producing model animal of hepatitis)
Seventeen C57BL/6J strain male mice (6 weeks old) were used.

(Test method)
Example 3
Eight mice were allowed to continuously ingest the same nutritional composition (Table 1) as in Experiment 1 ad libitum for 14 days (2 weeks) as a test feed. Hepatitis was then induced by administering 11 mg/kg-body weight (11 mg/kg mouse body weight) of Concanavalin A (ConA) into the tail vein of the mice.

Comparative example 3
Nine mice were allowed to freely ingest a general liquid diet (Meibalance HP, manufactured by Meiji Co., Ltd.) as a test feed continuously for 14 days (2 weeks). Hepatitis was then induced by administering 11 mg/kg-body weight (11 mg/kg mouse body weight) of Concanavalin A (ConA) into the tail vein of the mice.

(evaluation)
Plasma aspartate aminotransferase (AST) activity and plasma alanine aminotransferase (ALT) activity were used as indicators of hepatitis. Plasma albumin and plasma total protein were used as indicators of nutritional status. Plasma TNF-α, plasma IL-6, and plasma MCP-1 were used as indices of inflammation. The measured values for each index of hepatitis, nutritional status, and inflammation were evaluated as mean ± standard deviation. In statistical analysis, using Comparative Example 3 as a control group, the Student's t-test was used when the variances were equal, and the Mann-Whitney test was used when the variances were unequal.

In Example 3, when the measured values of each index of hepatitis were lower than those in Comparative Example 3, it means that hepatitis was suppressed in Example 3. On the other hand, in Example 3, when the measured value of each index of nutritional status is higher than in Comparative Example 3, deterioration of nutritional status is prevented and/or reduced in Example 3. In Example 3, when the measured value of each index of inflammation is lower than in Comparative Example 3, inflammation is suppressed.

Plasma TNF-α, plasma IL-6, and plasma MCP-1 were measured by collecting blood from the tail vein of each mouse at 2 and 4 hours after administration of ConA into the tail vein of each mouse. Blood was used. On the other hand, for the measurement of plasma AST activity, plasma ALT activity, plasma albumin, and plasma total protein, 24 hours after administration of ConA into the tail vein of each mouse, the abdomen of each mouse was placed under ether anesthesia. Blood was collected from a vein and this blood was used.

Dedicated slide chips (Fuji Drychem NX500, manufactured by Fuji Film Co., Ltd.) were used to measure plasma AST activity, plasma ALT activity, plasma albumin, and plasma total protein. Cytometric Bead Array (CBA) Mouse Inflammation kit (Nippon Becton Dickinson) was used to measure plasma TNF-α, plasma IL-6 and plasma MCP-1.

Evaluation results of hepatitis Plasma AST activity 24 hours after administration of ConA to the tail vein of mice in Example 3 and Comparative Example 3 is shown in FIG. As can be seen from FIG. 9, in Example 3, the plasma AST activity was significantly lower than in Comparative Example 3.

FIG. 10 shows the plasma ALT activity 24 hours after administration of ConA to the tail vein of mice in Example 3 and Comparative Example 3. As can be seen from FIG. 10, plasma ALT activity was significantly lower in Example 3 than in Comparative Example 3.

Results of evaluation of nutritional status Table 2 shows plasma albumin concentration and plasma total protein concentration 24 hours after administration of ConA to the tail vein of mice in Example 3 and Comparative Example 3. As can be seen from Table 2, in Example 3, the concentrations of plasma albumin and plasma protein tended to be higher than in Comparative Example 3.

In addition, it is generally believed that when pneumonia is induced in mice by administering ConA to the tail vein of mice, the concentration of plasma albumin decreases.

Evaluation Results of Inflammation Plasma TNF-α concentrations 2 hours and 4 hours after administration of ConA to the tail vein of mice in Example 3 and Comparative Example 3 are shown in FIG. As can be seen from FIG. 11, in Example 3, the plasma TNF-α concentration was significantly lower than in Comparative Example 3.

FIG. 12 shows plasma IL-6 concentrations 2 hours and 4 hours after administration of ConA to the tail vein of mice in Example 3 and Comparative Example 3. As can be seen from FIG. 12, in Example 3, the plasma IL-6 concentration was significantly lower than in Comparative Example 3.

FIG. 13 shows the respective plasma MCP-1 concentrations 2 hours and 4 hours after administration of ConA to the tail vein of mice in Example 3 and Comparative Example 3. As can be seen from FIG. 13, in Example 3, the plasma MCP-1 concentration was significantly lower than in Comparative Example 3.

(Discussion)
In Example 3 (mice that orally ingested the nutritional composition shown in Table 1), compared to Comparative Example 3 (mice that did not orally ingest the nutritional composition shown in Table 1), the measured values of each index were lower. Met. From this, it can be seen that the nutritional composition according to the present disclosure prevents and/or reduces deterioration of hepatitis, nutritional status, and inflammation caused by hepatitis over time. That is, it was confirmed that the nutritional composition according to the present disclosure has an anti-inflammatory (anti-inflammatory) effect.

[Experiment 4. Evaluation test of nutritional composition using hepatitis model animal (2)]
Nineteen C57BL/6J strain male mice (6 weeks old) were used.

(Test method)
Example 4-1
A mixture of a liquid nutritional composition according to the present disclosure and a general liquid diet (Meibalance HP, manufactured by Meiji Co., Ltd.) as a test feed for 7 mice (nutrition composition: liquid diet = 50: 50 ( Weight ratio))) was continuously fed ad libitum for 14 days. Hepatitis was then induced by administering concanavalin A (ConA) at 12 mg/kg-body weight (12 mg/kg body weight of mouse) into the tail vein of mice. Table 3 shows the compositions of the nutritional compositions used in Examples 4-1 and 4-2.

The pH of the nutritional composition shown in Table 3 is 4.1. The caloric density of this nutritional composition is 159 kcal/100 ml. The protein energy ratio of this nutritional composition is 20%. The protein source of this nutritional composition contains 4.2 g/100 kcal whey protein and 0.6 g/100 kcal whey peptides. The ratio of the combined weight of whey protein and whey peptides to the total weight of protein source of this nutritional composition is 96% by weight. EPA is 0.098 g/100 kcal. DHA is 0.035 g/100 kcal.

Example 4-2
Six mice with hepatitis were allowed to freely ingest the same nutritional composition (Table 3) as in Example 4-1 as a test feed for 14 consecutive days.

Comparative example 4
Six mice with hepatitis were allowed to freely ingest a general liquid diet (Meibalance HP, manufactured by Meiji Co., Ltd.) as a test feed continuously for 14 days.

(evaluation)
Plasma AST activity and plasma ALT activity were used as indicators of hepatitis. Plasma albumin and plasma total protein were used as indicators of nutritional status. Plasma TNF-α and plasma IL-6 were used as indices of inflammation. Here, the measured values for each index of hepatitis, nutritional status, and inflammation were evaluated by means±standard deviation. In the statistical analysis, using Comparative Example 4 as a control group, the Student's t-test was used when the variances were equal, and the Mann-Whitney test was used when the variances were unequal. The same method as in Experiment 3 was used to measure each index.

Evaluation results of hepatitis Plasma AST activity 24 hours after administration of ConA to the tail vein of mice in Examples 4-1 to 4-2 and Comparative Example 4 is shown in FIG. As can be seen from FIG. 14, the plasma AST activity was significantly lower in Examples 4-1 and 4-2 than in Comparative Example 4.

FIG. 15 shows plasma ALT activity 24 hours after administration of ConA to the tail vein of mice in Examples 4-1 to 4-2 and Comparative Example 4. As can be seen from FIG. 15, plasma ALT activity was significantly lower in Examples 4-1 and 4-2 than in Comparative Example 4.

Evaluation results of nutritional status Table 4 shows plasma albumin concentration and plasma total protein concentration 24 hours after administration of ConA to the tail vein of mice in Examples 4-1 to 4-2 and Comparative Example 4. shown in As can be seen from Table 4, plasma albumin concentrations tended to be higher in Example 4-1 than in Comparative Example 4. In Example 4-2, the concentration of plasma albumin was significantly higher than in Comparative Example 4. In Examples 4-1 and 4-2, the plasma total protein concentration tended to be higher than in Comparative Example 4.

Results of evaluation of inflammation Plasma TNF-α concentrations 2 hours and 4 hours after administration of ConA to the tail vein of mice in Examples 4-1 to 4-2 and Comparative Example 4 are shown in FIG. show. As can be seen from FIG. 16, plasma TNF-α concentrations were significantly lower in Examples 4-1 and 4-2 than in Comparative Example 4.

FIG. 17 shows plasma IL-6 concentrations 2 hours and 4 hours after administration of ConA to the tail vein of mice in Examples 4-1 to 4-2 and Comparative Example 4. As can be seen from FIG. 17, plasma IL-6 concentrations were significantly lower in Examples 4-1 and 4-2 than in Comparative Example 4.

(Discussion)
In Examples 4-1 and 4-2 (mice that orally ingested the nutritional composition shown in Table 3), compared with Comparative Example 4 (mice that did not orally ingest the nutritional composition shown in Table 3), The measured value of each index was low. From this, it can be seen that the nutritional composition according to the present disclosure prevents and/or reduces deterioration of hepatitis, nutritional status, and inflammation caused by hepatitis over time. That is, it was confirmed that the nutritional composition according to the present disclosure has an anti-inflammatory (anti-inflammatory) effect.

[Experiment 5. Flavor and physical property evaluation test of fresh and preserved products of nutritional compositions]
The flavor and physical properties of fresh and preserved nutritional compositions shown in Table 5 were evaluated.

The pH of the nutritional composition shown in Table 5 is 4.1. The caloric density of this nutritional composition is 151 kcal/100 ml. The protein energy ratio of this nutritional composition is 21%. The protein source of this nutritional composition includes 2.4 g/100 kcal whey protein and 2.5 g/100 kcal whey peptides. The ratio of the combined weight of whey protein and whey peptides to the total weight of protein source of this nutritional composition is 96% by weight. EPA is 0.157 g/100 ml. DHA is 0.056 g/100 ml.

The manufacturing conditions for the nutritional composition shown in Table 5 are as follows: dissolution temperature of preparation (raw material): 50 to 60 ° C. (target: 55 ° C.), sterilization temperature and time of preparation: 124 ° C., 5 seconds, homogenization of sterilization solution Homogenization pressure: 40 MPa (preliminary homogenization), 25 MPa (main homogenization), container shape and volume: brick paper container (manufactured by Tetra), 125 ml. In addition, each nutritional composition shown in Tables 1 and 3 was also manufactured under the same manufacturing conditions.

(Test method)
The flavor and physical properties of the fresh and preserved nutritional compositions shown in Table 5 (3 months storage, 6 months storage) were evaluated.

flavor

The flavor of the fresh product and the preserved product of the nutritional composition was sensory evaluated by a panel of 10 experts on a scale of 5 (5: very good, 4: good, 3: fair, 2: somewhat poor, 1: poor). .

The physical properties of fresh and preserved physical nutritional compositions were evaluated in terms of specific gravity, pH, viscosity, particle size distribution, centrifugal sedimentation amount, and cream flotation rate.

In measuring the specific gravity of fresh and preserved nutritional compositions, the samples were adjusted to 20° C., and then a density hydrometer (DA-130N, manufactured by Kyoto Electronics Industry Co., Ltd.) was used.

In measuring the pH of fresh and preserved nutritional compositions, a pH meter (F-53, manufactured by Horiba, Ltd.) was used after adjusting the sample to 20°C.

The viscosities of fresh and stored nutritional compositions were measured using a B-type rotational viscometer (TVB10, manufactured by Toki Sangyo Co., Ltd.) after the samples were adjusted to 20°C. The operating conditions were rotation speed: 60 rpm and holding time: 60 seconds.

A laser refractive particle size distribution analyzer (SALD-2200, manufactured by Shimadzu Corporation) was used to measure the particle size distribution of fresh and preserved nutritional compositions. In addition, this index was taken as the median diameter (median value).

The following method was used to measure the amount of centrifugal sediment in fresh and preserved nutritional compositions. First, the weight of a glass centrifuge tube (50 ml, round bottom, transparent centrifuge tube with a horizontal line drawn in the center (1/2 of the total height and 5 cm from the top)) is measured, and 50 g of each sample (sample Amount) is accurately weighed. Subsequently, after centrifuging the glass centrifuge tube (containing the sample) (1800 g, 30 minutes), the liquid surface is gently discarded by decantation. Furthermore, after inverting the glass centrifuge tube (with sediment) and allowing it to stand for 30 minutes, wipe the inner wall surface of the glass centrifuge tube from the top to the horizontal line with Kimwipe, and then measure the weight of the glass centrifuge tube (with residue). do. Then, the centrifugal sedimentation amount is calculated by the following formula (1).

Amount of centrifugal sediment [% by weight] = (weight of centrifuge tube (with residue) [g] - weight of centrifuge tube (tare) [g]) / weight of sample [g] x 100 (1)
The following method was used to measure the cream floating rate of fresh and preserved nutritional compositions. First, the weight of a glass centrifuge tube (50 ml, round bottom, transparent centrifuge tube with a horizontal line drawn in the center (1/2 of the total height and 5 cm from the top)) is measured, and 50 g of each sample (sample Amount) is accurately weighed. Subsequently, after the glass centrifuge tube (containing the sample) is centrifuged (1800 g, 30 minutes), the cream layer (upper portion) is taken out into another glass centrifuge tube with a spatula. Furthermore, after inverting the glass centrifuge tube (with cream layer) and allowing it to stand for 30 minutes, wipe the inner wall surface of the glass centrifuge tube from the top to the horizontal line with Kimwipe, then weigh the glass centrifuge tube (with residue). Measure. Then, the cream floating rate is calculated by the following formula (2).

Cream flotation rate [% by weight] = (weight of centrifuge tube (with residue) [g] - weight of centrifuge tube (tare) [g]) / weight of sample [g] x 100 (2)
(evaluation)
Table 6 shows the evaluation criteria for flavor and physical properties, and the evaluation values of fresh and preserved nutritional compositions (Table 5) used in Experiment 5 (3 months storage, 6 months storage). When the evaluation values of the fresh and preserved nutritional composition satisfy each evaluation criterion, it means that the flavor and physical properties of the nutritional composition are good.

The specific gravity of the nutritional composition is preferably 1.1 to 1.2 g/cm ³ from the viewpoint that the nutritional composition can be drunk in a small amount and a large amount of energy can be ingested. The pH of the nutritional composition is preferably 3 to 5 from the viewpoints that sterilization conditions can be set moderately and moderate sourness (flavor) can be obtained. The viscosity of the nutritional composition is preferably 10 to 100 mPs·s from the viewpoints of suppressing or preventing scorching and the like in production equipment and having good fluidity. The particle size distribution (median diameter) of the nutritional composition is preferably 10 µm or less from the viewpoint of improving the emulsion stability. The centrifugal sedimentation amount of the nutritional composition is preferably 3% by weight or less from the viewpoint of improving the emulsion stability. The cream floating rate of the nutritional composition is preferably 5% by weight or less from the viewpoint of maintaining good physical properties and quality.

flavor

As shown in Table 6, the flavor of the fresh nutrient composition and the preserved product (storage conditions: 25°C, 3 months storage) were evaluated to be very good. The flavor of the stored nutritional composition (storage conditions: 25° C., 6 months storage) was evaluated as good.

As shown in physical properties Table 6, the specific gravity, pH, viscosity, particle size distribution, The centrifugal sedimentation amount and cream floating rate satisfied the evaluation criteria. That is, in the nutritional composition according to the present disclosure, the physical properties of the nutritional composition hardly changed even after being stored at room temperature for a long period of time.

(Discussion)
The nutritional composition shown in Table 5 has good flavor and physical properties not only for fresh products but also for preserved products (storage conditions: 25 ° C. for 3 months and storage conditions: 25 ° C. for 6 months). It was confirmed that That is, although the nutritional composition according to the present disclosure contains ingredients that affect flavor and physical properties such as fish oil (DHA and EPA), even if it is stored at room temperature for a long period of time, It was confirmed that the flavor was good and the physical properties were stable.

Claims (10)

A flowable nutritional composition comprising:
containing a protein source comprising whey protein and whey peptides;
The ratio of the sum of the weight of the whey protein and the weight of the whey peptides to the total weight of the protein source is 80% by weight or more,
The ratio of the whey protein weight to the whey peptide weight is 2.5:2.3 to 1:10,
a protein energy ratio of 16% or more and less than 50%,
having a calorie density of 100 kcal/100 ml or more,
containing 1 to 100 mg/100 kcal of EPA and 1 to 100 mg/100 kcal of DHA,
A nutritional composition that is acidic. A nutritional composition according to claim 1,
A nutritional composition, wherein the nutritional composition has a pH of 3 or more and 5 or less. A nutritional composition according to claim 2,
A nutritional composition further comprising zinc. A nutritional composition according to claim 2,
A nutritional composition, wherein the protein source further comprises leucine. A nutritional composition according to any one of claims 1 to 4,
A nutritional composition, which is a nutritional composition for rehabilitation nutrition. A nutritional composition according to any one of claims 1 to 4,
A nutritional composition for preventing and/or improving chronic obstructive pulmonary disease. A nutritional composition according to any one of claims 1 to 4,
A nutritional composition, which is an anti-inflammatory nutritional composition. A nutritional composition according to any one of claims 1 to 7,
A nutritional composition further comprising palatinose as a carbohydrate. A nutritional composition according to claim 8,
A nutritional composition containing 10 to 16 g/100 kcal of the palatinose. A nutritional composition according to claim 8,
A nutritional composition containing the palatinose in an amount of 20% by weight or more of the total carbohydrates.

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