Composition for improving kidney function

Abstract

Providing technologies to improve kidney function. [Solution] A composition for improving renal function, comprising a whey protein hydrolysate having the following physicochemical properties (1) to (3): (1) The average molecular chain length of the whey protein hydrolysate is 2 to 10. (2) The fraction of the whey protein hydrolysate with a molecular weight of 5,000 to 10,000 daltons accounts for 8% or less of the total whey protein hydrolysate. (3) The amount of free amino acids relative to the total amount of amino acids in the whey protein hydrolysate is 10% or less.

Description

【Technical Field】 【0001】 The present disclosure relates to a composition for improving renal function. 【Background Art】 【0002】 Kidney diseases other than acute nephritis are lifelong diseases, and may eventually lead to end-stage renal failure (a state where dialysis is required). Since the kidneys have a significant reserve capacity, chronic kidney damage is mostly asymptomatic until its function drops below 20%. That is, when symptoms appear, there is a high possibility of end-stage renal failure, and in many cases, the symptoms have progressed to the stage where dialysis is necessary. 【0003】 Currently, the number of chronic dialysis patients is said to be about 200,000, and more than 30,000 new dialysis introductions occur every year. For chronic kidney disease (CKD), the goal is to slow down the progression of the disease and keep renal function intact for as long as possible, and there is no treatment to cure the disease itself. Currently, dietary therapy and drug therapy for renal failure are used to suppress the progression of the disease and prolong the remaining function of the kidneys. 【0004】 Under such circumstances, the development of drugs and compositions having an effect of preventing or improving renal function impairment is required. In contrast, for example, a renal function improver containing a specific synthetic compound has been developed (Patent Document 1). Also, a composition for increasing renal function that reduces creatinine and BUN levels in a subject, containing a specific type of probiotic bacteria, has been developed (Patent Document 2). 【0005】 On the other hand, a blood uric acid level reducing agent containing a whey protein hydrolyzate having specific physicochemical properties as an active ingredient has been developed (Patent Document 3). Hyperuricemia may be complicated with gout or metabolic syndrome, and may also be complicated with renal function impairment. However, for example, there is no causal relationship such that improvement of renal function is achieved by reducing blood uric acid levels. 【Prior Art Documents】 [Patent Documents] 【0006】 [Patent Document 1] Special Publication No. 2011-509941 [Patent Document 2] Japanese Patent Publication No. 2013-209396 [Patent Document 3] Japanese Patent Publication No. 2019-043871 [Overview of the Initiative] [Problems that the invention aims to solve] 【0007】 This disclosure aims to provide technology for improving renal function. [Means for solving the problem] 【0008】 The inventors have found that whey protein hydrolysates having specific physicochemical properties can solve the aforementioned problems. 【0009】 This disclosure can provide the following: [1] A composition for improving renal function, comprising a whey protein hydrolysate having the following physicochemical properties (1) to (3). (1) The average molecular chain length of whey protein hydrolysates is 2 to 10. (2) The fraction of whey protein hydrolysate with a molecular weight of 5,000 to 10,000 daltons accounts for 8% or less of the total whey protein hydrolysate. (3) The amount of free amino acids relative to the total amount of amino acids in the whey protein hydrolysate is 10% or less. [2] The composition according to [1], which reduces blood creatinine levels and / or increases estimated glomerular filtration rate. [3] The composition according to [1] or [2], for use with subjects having a GFR classification of G2, and / or subjects having a GFR classification of G3. [4] The composition according to [3], wherein the subject whose GFR classification is G3 is a subject whose GFR classification is G3a. [5] A food and beverage composition, as described in any of [1] to [4]. [6] A pharmaceutical composition, as described in any of [1] to [4]. [Effects of the Invention] 【0010】 This disclosure provides a technology for improving renal function. Furthermore, this disclosure provides a composition for improving renal function that can be safely consumed over a long period of time. [Modes for carrying out the invention] 【0011】 The details of this disclosure are described below. However, this disclosure is not limited to the following forms and may be freely modified within the scope of this disclosure. 【0012】 In this disclosure, percentages are expressed in terms of mass unless otherwise specified. In this disclosure, words such as "ingestion," "ingestion," and "ingested" can be replaced with words such as "administration," "being administered," and "administered," respectively. In this disclosure, "X~Y" indicating a range means "X or greater and Y or less". Furthermore, when numerical ranges expressed as "X~Y" or "X or greater and Y or less" are listed in stages (for example, in preferred order), the upper and lower limits of each numerical range can be any combination. In this disclosure, any phrase such as "one or more selected from the group consisting of X, Y, and Z" means any of X, Y, Z, a combination of X and Y, a combination of X and Z, a combination of Y and Z, or a combination of X, Y, and Z. In this disclosure, any mention of "X such as x1, x2, and x3" is merely an example of X, and does not imply that X is limited to x1, x2, and x3. 【0013】 One aspect of the present disclosure is a composition for improving renal function, comprising a whey protein hydrolyzate having the following physicochemical properties (1) to (3). (1) The average molecular chain length of the whey protein hydrolyzate is 2 to 10. (2) The fraction of the whey protein hydrolyzate with a molecular weight of 5,000 to 10,000 daltons is 8% or less of the total whey protein hydrolyzate. (3) The amount of free amino acids relative to the total amount of amino acids in the whey protein hydrolyzate is 10% or less. 【0014】 The composition of this aspect may contain only the whey protein hydrolyzate. However, it may also contain other components that exhibit the effect of improving renal function when in the form of a composition. When the composition of this aspect contains such other components, the composition of this aspect may be a mixture of the whey protein hydrolyzate and the other components, and these components may be homogeneous or heterogeneous. 【0015】 The whey protein hydrolyzate in this aspect is obtained by hydrolyzing whey protein derived from milk. Whey protein contains various components, and the hydrolyzate of this aspect is the result of hydrolyzing these components. Examples of the hydrolysis include those by one or more selected from the group consisting of proteolytic enzymes, acids, and alkalis. Examples of whey protein include commercially available products, or whey separated from milk or skim milk by known methods (for example, whey powder, demineralized whey powder, etc.), separated and purified whey protein concentrate (WPC), whey protein isolate (WPI), and mixtures of these in any ratio. In this aspect, it is preferable to use whey protein derived from milk. Also, the whey protein is preferably whey protein concentrate (WPC). Whey protein derived from milk is generally known to contain 15-25% α-lactalbumin, 50-65% β-lactoglobulin, 5-10% bovine serum albumin, lactoferrin, etc. The same is true for whey protein concentrate (WPC) and whey protein isolate (WPI). 【0016】 In this embodiment, the whey protein hydrolysate is preferably a whey protein hydrolysate obtained by hydrolysis with a protein hydrolase (hereinafter sometimes referred to as "whey protein enzyme hydrolysate"). 【0017】 Examples of methods for producing whey protein enzyme hydrolysates in this embodiment are given below, but are not limited thereto. Specifically, first, the whey protein, which is the raw material, is dispersed in water or warm water and dissolved to prepare a whey protein solution. While there are no restrictions on the concentration of the whey protein solution, it is generally preferable, from the standpoint of efficiency and ease of handling, to set the protein concentration in the range of 2-20%, preferably 5-15%. A dissolution concentration of 2% or higher improves manufacturing efficiency, while a dissolution concentration of 20% or lower can suppress the risk of decreased decomposition efficiency, scorching during heat treatment, and increased viscosity during cooling, which is desirable. 【0018】 It is preferable to adjust the pH of the whey protein solution using an acid or alkali solution so that it falls within the optimal pH range for the protein hydrolase used in this embodiment. It is desirable to adjust the pH of the whey protein solution to between 6.5 and 10.0 before hydrolysis. Furthermore, as a pre-hydrolysis treatment step, heat treatment, ion exchange treatment, etc. may be performed before, after, or both of the pH adjustment steps. 【0019】 Hydrolysis is carried out by adding a protein hydrolase to a whey protein solution whose pH has been adjusted as appropriate. The protein hydrolase used in the production of the whey protein hydrolysate in this embodiment is not particularly limited, but is preferably a protease, more preferably an endoprotease, and may be used in combination with an exoprotease as needed. In this embodiment, one enzyme may be used, or multiple enzymes may be used in combination. Examples of endoproteases used in this embodiment include bioprases (Nagase Biochemical Co., Ltd.). Examples of commercially available products include (manufactured by Amano Enzyme Co., Ltd.), Protin SD-AY10 (manufactured by Amano Enzyme Co., Ltd.), Protin NY100 (manufactured by Amano Enzyme Co., Ltd.), Protease N Amano (manufactured by Amano Enzyme Co., Ltd.), Nutrase (manufactured by Novo Nordisk), Alcalase (manufactured by Novo Nordisk), Trypsin (manufactured by Novo Nordisk), Chymotrypsin (manufactured by Novo Nordisk), Papain (manufactured by Amano Enzyme Co., Ltd.), and Bromelain (manufactured by Amano Enzyme Co., Ltd.). Furthermore, examples of commercially available exoproteases used in this embodiment include Protease A Amano (manufactured by Amano Enzyme Co., Ltd.), Sumizyme LP50D (manufactured by Shin Nippon Kagaku Kogyo Co., Ltd.), and Flavorzyme (manufactured by Novo Nordisk). 【0020】 Whey protein solutions to which protein hydrolase has been added are preferably hydrolyzed under predetermined processing conditions. Specifically, it is desirable to hydrolyze them by maintaining the temperature at the optimal temperature for the enzyme used for a predetermined time. The optimal temperature is preferably 30 to 60°C, more preferably 40 to 55°C, and the processing time is preferably 2 to 24 hours, more preferably 3 to 12 hours. The whey protein solution is preferably kept warm in this temperature range for a certain period of time and hydrolyzed by enzymes. Furthermore, the pH of the whey protein solution at this time is preferably adjusted to pH 6 to 11, more preferably to 6.5 to 10, and even more preferably to 7 to 9. Enzymes can be added simultaneously or at appropriate intervals, and immobilized enzymes can also be used. Furthermore, the pH of the solution can be adjusted as needed during hydrolysis to maintain the optimal pH for the enzymes. 【0021】 Furthermore, when whey protein solution is hydrolyzed by batch processing, the hydrolyzed solution is heat-treated by conventional methods to inactivate the enzymes. The heating temperature and holding time should be set appropriately, taking into account the thermal stability of the enzymes used, to ensure sufficient inactivation. After heat treatment, the solution can be cooled by conventional methods, and either used as is or concentrated as needed, dried, and a powder product can be obtained. 【0022】 The whey protein hydrolysate in this embodiment can be appropriately adjusted and manufactured by the previously described method so as to have the physicochemical properties of (1) to (3) above. 【0023】 In this embodiment, the whey protein hydrolysate preferably has one or more physicochemical properties selected from the group consisting of (4) to (6) below. (4) The transmittance at 540 nm in a 10% whey protein hydrolysate solution is 95% or higher. (5) When a 5% by mass whey protein hydrolysate solution is heated at pH 4-7 at 120°C for 10 minutes, no precipitate is formed. (6) A 5% by mass whey protein hydrolysate solution does not gel when heated at 85°C for 10 minutes in the presence of 0.025 mol / L calcium chloride at pH 3-5. 【0024】 The average molecular chain length of the whey protein hydrolysate is preferably 2 to 10, and more preferably 3 to 5. The average molecular chain length of the whey protein hydrolysate can be measured by the TNBS method (see "3) TNBS method for measuring average peptide chain length" in "Journal of the Japanese Society of Nutrition and Food Science, Vol. 47, No. 3, 195-201 (1994)"). 【0025】 Of the whey protein hydrolysates, the fraction with a molecular weight of 5,000 to 10,000 daltons is preferably 8% or less of the total whey protein hydrolysates, more preferably 5% or less, and even more preferably 2% or less. The molecular weight of the whey protein hydrolysate can be measured by the <Measurement of Molecular Weight Distribution> described below. 【0026】 <Measurement of molecular weight distribution> The molecular weight distribution is measured by high-performance liquid chromatography (edited by Nobuo Ui et al., "High-Performance Liquid Chromatography of Proteins and Peptides," Chemical Society Special Issue No. 102, p. 241, Kagaku Dojin Co., Ltd., 1984). Specifically, a polyhydroxyethyl aspartamide column (Poly LC, 4.6 mm in diameter and 220 mm in length) was used, and elution was performed with 20 mM sodium chloride and 50 mM formic acid at an elution rate of 0.5 mL / min. Detection is performed using a UV detector (manufactured by Shimadzu Corporation), and data analysis is performed using a GPC analysis system (manufactured by Shimadzu Corporation). [Percentage of each molecular weight fraction (%)] = [Area of ​​each molecular weight range in the molecular weight distribution / Total area of ​​whey protein hydrolysate in the molecular weight distribution (total area)]. 【0027】 The amount of free amino acids relative to the total amount of amino acids in the whey protein hydrolysate is preferably 10% or less, more preferably 8% or less, and even more preferably 6% or less. The aforementioned whey protein hydrolysate is superior in that, because the amount of free amino acids relative to the total amount of amino acids is within the aforementioned range, the characteristic flavor of amino acids is hardly noticeable. Therefore, the whey protein hydrolysate used in this embodiment exhibits a good flavor even when consumed alone without being mixed with other foods or beverages. The amount of free amino acids contained in the whey protein hydrolysate used in this embodiment can be measured by the following formula: Total mass percentage of free amino acids (%) = (Mass of total free amino acids / Mass of total amino acids) × 100 (see <Method for calculating amino acid release rate> described in Japanese Patent Publication No. 2017-31105). 【0028】 The whey protein hydrolysate used in this embodiment preferably has a transmittance of 95% or more, and more preferably 97% or more, at 540 nm in a 10% by mass whey protein hydrolysate solution. The 10% by mass whey protein hydrolysate solution is obtained by dissolving powdered whey protein hydrolysate in water to make a 10% by mass (mass / volume) aqueous solution. The fact that the transmittance at 540 nm in a 10% by mass whey protein hydrolysate solution is within the aforementioned range means that the solution is transparent, which is advantageous as it allows for application in a wide range of products such as food and pharmaceuticals. 【0029】 In this embodiment, it is preferable that the whey protein hydrolysate used does not produce precipitate when a 5% by mass whey protein hydrolysate solution (pH adjusted to 4-7) is heated at 120°C for 10 minutes. Furthermore, it is preferable that the whey protein hydrolysate used in this embodiment does not gel even after adding calcium chloride to a concentration of 0.025 mol / L, adjusting the pH to 3-5 to make a 5% by mass aqueous solution, and then heating it at 85°C for 10 minutes. The 5% by mass whey protein hydrolysate solution is prepared by converting powdered whey protein hydrolysate into a 5% by mass (mass / volume) aqueous solution. 【0030】 Furthermore, the whey protein hydrolysate in this embodiment is highly soluble in water, exhibits excellent processing stability, has little bitterness, and has a good flavor. In addition, since whey protein is empirically known to be highly safe, it can be consumed continuously for a long period of time with peace of mind. 【0031】 The target of ingesting the composition according to this embodiment is a human being. This human being may be male or female. 【0032】 Kidney function includes, for example, the function of eliminating waste products from the body, regulating blood pressure, secreting erythropoietin to produce red blood cells, regulating body fluid volume and ion balance, and producing active vitamin D which allows calcium to be absorbed into the body. 【0033】 When kidney function declines, for example, glomerular filtration may decrease and blood creatinine levels may rise. The glomeruli play a central role in kidney function, and glomerular filtration rate (GFR) and estimated glomerular filtration rate (eGFR), which indicate their function, are known to be indicators of kidney function. When GFR or eGFR decreases, the kidneys are unable to adequately excrete metabolites and other substances. Creatinine is a waste product of protein found in muscles. Normally, it is filtered by the glomeruli of the kidneys and excreted in the urine. However, when kidney function declines, the amount excreted in the urine decreases, and creatinine accumulates in the blood. Therefore, as kidney function declines, blood creatinine levels increase. Therefore, renal function can generally be evaluated using serum creatinine levels (sometimes referred to as "serum creatinine levels") as an indicator, or using estimated glomerular filtration rate (eGFR) calculated from sex, age, and serum creatinine levels as an indicator. In addition to these, glomerular filtration rate (GFR), blood urea nitrogen (BUN), creatinine clearance, etc., can also be used as indicators. When evaluating renal function, one of these indicators may be used, or multiple indicators may be used. 【0034】 The composition of this embodiment can preferably reduce blood creatinine levels and / or increase the estimated glomerular filtration rate (eGFR) in subjects who ingest it. 【0035】 The composition of this embodiment is preferably used for subjects whose renal function improves upon ingestion of the composition of this embodiment. As shown in the examples described later, it is preferably for subjects with a GFR classification of G2 and / or subjects with a GFR classification of G3. Subjects with a GFR classification of G3 may be subjects with a GFR classification of G3a and / or subjects with a GFR classification of G3b. Subjects classified as G2 in the GFR category are those with an eGFR of 60-89 mL / min / 1.73 m². 2 This refers to subjects whose GFR classification is G3, and subjects whose eGFR is 30-59 mL / min / 1.73 m² 2 This refers to subjects whose GFR classification is G3a, and subjects whose eGFR is 45-59 mL / min / 1.73 m² 2 This refers to subjects whose GFR classification is G3b, and subjects whose eGFR is 30-44 mL / min / 1.73 m² 2 It refers to an object that is [that]. 【0036】 The whey protein hydrolysate in this embodiment has a renal function improving effect, as will be shown in the examples described later. Therefore, the composition in this embodiment can be used to improve renal function. Furthermore, the composition of this embodiment can be used to prevent or treat diseases, signs, symptoms, or disorders (in this disclosure, "diseases, signs, symptoms, or disorders" may be referred to as "diseases, etc.") that can be prevented or treated by improving renal function. The diseases in question may be those caused by a decline in renal function. For example, the following diseases introduced by the Japanese Society of Nephrology can be cited: acute kidney injury, chronic kidney disease, tubulointerstitial nephritis, drug-induced kidney injury (e.g., toxic kidney injury, hypersensitivity kidney injury, renal blood flow disorder, etc.), glomerulonephritis (IgA nephropathy, acute glomerulonephritis, rapidly progressive glomerulonephritis, minimal change nephrotic syndrome, membranous nephropathy, membranoproliferative glomerulonephritis, focal segmental glomerulosclerosis, etc.), renal impairment associated with systemic diseases (diabetes-related kidney disease, lupus nephritis, amyloidosis, ANCA-associated vasculitis, These include anti-glomerular basement nephritis, IgA vasculitis, gouty nephritis, polycystic kidney disease, Fabry disease, IgG4-related kidney disease, nephrosclerosis, pregnancy-related kidney damage, etc., edema (swelling), decreased urine output, frequent urination (including nocturia), fatigue, anemia, itchy skin, cardiovascular complications (CVD), bone mineral metabolism disorders, congenital renal and urinary tract abnormalities (CAKUT), cystic kidney disease, tubular disorders, hereditary glomerular disorders (Alport syndrome, etc.), and fatigue. 【0037】 When the composition of this embodiment is used for subjects with a GFR classification of G2 and / or subjects with a GFR classification of G3, the disease or the like may be, for example, chronic kidney disease. 【0038】 The composition of this embodiment may be used for non-therapeutic purposes or for therapeutic purposes. "Non-therapeutic purposes" refer to purposes that do not involve medical procedures. In other words, purposes that do not involve treatment or intervention on the subject. Examples include purposes for maintaining or promoting health. 【0039】 When the composition of this embodiment is used for non-therapeutic purposes, it can be used on healthy individuals. "Healthy person" means a person who, at the time of ingesting the composition of this embodiment, does not have a disease or other condition that can be prevented or treated by improving renal function (for example, a person who is not a patient with a disease or other condition that can be prevented or treated by improving renal function), and may include a person who is concerned about such a disease or other condition, or a person who is prone to such a disease or other condition. When the composition of this embodiment is used for non-therapeutic purposes, it may improve renal function in healthy individuals. Furthermore, it may help prevent such diseases in healthy individuals. 【0040】 When the composition of this embodiment is used for therapeutic purposes, it may be used on non-healthy individuals. "Non-healthy person" may refer to a person who, at the time of ingesting the composition of this embodiment, has a disease or other condition that can be treated by improving renal function (for example, a patient with a disease or other condition that can be treated by improving renal function). When the composition of this embodiment is used for therapeutic purposes, it may improve renal function in non-healthy individuals. Furthermore, it may be used to treat diseases or other conditions in non-healthy individuals. 【0041】 Furthermore, symptoms resulting from decreased kidney function may be classified into "symptoms caused by diseases, etc." and "symptoms caused by factors other than diseases, etc." For example, in the case of food and beverage compositions (e.g., health foods and beverages), they may be intended for "symptoms caused by factors other than diseases, etc." and may be targeted at healthy individuals. 【0042】 Furthermore, symptoms observed in diseases that can be prevented or treated by improving kidney function may be classified into "symptoms caused by the disease" and "symptoms caused by factors other than the disease." For example, in the case of food and beverage compositions (e.g., health foods and beverages), they may be for "symptoms caused by factors other than the disease" and may be targeted at healthy individuals. To explain with a specific example, the symptom of fatigue can be divided into "fatigue caused by disease, etc." and "fatigue caused by something other than disease, etc." For example, in the case of food and beverage compositions (e.g., health foods and beverages), they may be intended for "fatigue caused by something other than disease, etc." and may be targeted at healthy individuals. Furthermore, the symptoms observed in acute kidney injury may be divided into "symptoms observed in acute kidney injury caused by diseases, etc." and "symptoms observed in acute kidney injury caused by factors other than diseases, etc." For example, in the case of food and beverage compositions (e.g., health foods and beverages), they may be intended for "symptoms observed in acute kidney injury caused by factors other than diseases, etc." and may be targeted at healthy individuals. 【0043】 Furthermore, the effect on "anemia," etc., in food and beverage compositions (for example, health foods and beverages), may be, for example, "helps maintain hemoglobin levels at a healthy level." The same applies to other effects, which may be "helpful in maintaining levels at a level similar to that of healthy individuals." 【0044】 This disclosure provides the use of the whey protein hydrolysate for producing a composition for improving renal function in healthy individuals (which may be a food or beverage composition, for example, a health food or beverage). Furthermore, this disclosure can provide the use of the whey protein hydrolysate for producing food and beverage compositions (e.g., health foods and beverages) that prevent or improve symptoms that appear in healthy individuals due to decreased renal function. Furthermore, this disclosure can provide the use of the whey protein hydrolysate for producing food and beverage compositions (e.g., health foods and beverages) that prevent or improve symptoms appearing in diseases that can be prevented or treated by improving renal function in healthy individuals. 【0045】 When the composition of this embodiment is used for non-therapeutic purposes, it may prevent or improve symptoms that appear in diseases, etc., that can be prevented or treated by improving renal function in healthy individuals. 【0046】 The content of the whey protein hydrolysate in the composition of this embodiment is set appropriately depending on the embodiment of the composition, for example, 5% or more, 10% or more, 20% or more, etc., while on the other hand, it may be 90% or less, 80% or less, 70% or less, etc. A non-inconsistent combination of these may also be acceptable. For example, 5-90%, 10-80%, 20-70%, etc. Furthermore, the content of the whey protein hydrolysate may be the content as a dry product. 【0047】 The proportion of the whey protein hydrolysate in the composition of this embodiment may be determined according to the amount of the composition consumed by the person ingesting it at one time and the amount of the whey protein hydrolysate contained in the composition of this embodiment. 【0048】 The intake amount (effective amount) of the composition in this embodiment is set appropriately depending on the form of the composition, method of use, target, target age, sex, and other conditions, but is not particularly limited as long as the renal function improving effect is exerted in the target who ingests it. For example, the amount of whey protein hydrolysate may be 2g / day or more, 5g / day or more, 8g / day or more, on the other hand, 50g / day or less, 20g / day or less, 12g / day or less, etc. Non-contradictory combinations of these may also be used. For example, 2-50g / day, 5-20g / day, 8-12g / day, etc. The conversion rate per kg of body weight could be, for example, 0.01 g / kg body weight / day or more, 0.05 g / kg body weight / day or more, while on the other hand, it could be 1 g / kg body weight / day or less, 0.5 g / kg body weight / day or less, etc. A non-contradictory combination of these is also acceptable. For example, 0.01 to 1 g / kg body weight / day, 0.05 to 0.5 g / kg body weight / day, etc. Furthermore, the amount of the whey protein hydrolysate may be the amount in dry form. 【0049】 The number of times the composition of this embodiment is taken per day is not particularly limited and can be appropriately determined according to the amount of the whey protein hydrolysate taken per day. The composition of this embodiment is preferably consumed consistently for a certain period of time. The period of consumption is preferably 8 weeks or more, more preferably 10 weeks or more, and even more preferably 12 weeks or more. 【0050】 The composition of this embodiment can be taken orally, but is not limited to this; for example, it may be taken nasally, or by gastrostomy or jejunostomy. For example, it may be taken to a subject via a nasogastric feeding tube or the like. 【0051】 The composition according to this embodiment can be used, for example, as a food or beverage composition or a pharmaceutical composition. For example, it can be provided as a food and beverage composition for improving renal function, containing the whey protein hydrolysate. Hereinafter, this may be referred to as "the food and beverage composition of this embodiment." It can also be provided as a pharmaceutical composition for improving renal function, containing the whey protein hydrolysate. Hereinafter, this may be referred to as "the pharmaceutical composition of this embodiment." 【0052】 The food and beverage composition of this embodiment is not particularly limited as long as it contains the whey protein hydrolysate. The food and beverage composition may be food or beverage in any form, such as liquid, paste, gel-like solid, or powder, and may include tablets, liquid foods, etc., as well as wheat flour products such as bread, macaroni, spaghetti, noodles, cake mix, fried chicken batter, breadcrumbs; instant foods such as instant noodles, cup noodles, retort / prepared foods, canned prepared foods, microwaveable foods, instant soups / stews, instant miso soup / clear soup, canned soups, freeze-dried foods, and other instant foods; canned agricultural products, canned fruits Processed agricultural products such as jams and marmalades, pickles, boiled beans, dried agricultural products, and cereals (grain processed products); processed marine products such as canned seafood, fish ham and sausages, processed seafood products, seafood delicacies, and tsukudani (simmered seafood); processed livestock products such as canned and paste products, and meat ham and sausages; processed milk, milk beverages, yogurts, lactic acid bacteria beverages, cheeses, ice creams, powdered milk, cream, and other dairy products; fats and oils such as butter, margarine, and vegetable oils; soy sauce, miso, and sausages. Basic seasonings such as vinegars, tomato-based seasonings, mirin, and vinegars; compound seasonings and foods such as cooking mixes, curry bases, sauces, dressings, noodle soup bases, spices, and other compound seasonings; frozen foods such as raw frozen foods, semi-cooked frozen foods, and cooked frozen foods; and confectionery such as caramel, candy, gummy candy, chewing gum, chocolate, cookies, biscuits, cakes, pies, snacks, crackers, Japanese sweets, rice sweets, bean sweets, dessert sweets, jelly, and other sweets. Examples of beverages include: carbonated drinks, natural fruit juices, fruit juice beverages, fruit juice-containing soft drinks, fruit pulp beverages, fruit juices with fruit pulp, vegetable beverages, soy milk, soy milk beverages, coffee beverages, tea beverages, powdered beverages, concentrated beverages, sports drinks, nutritional beverages, alcoholic beverages, and other beverages for enjoyment; baby food, furikake (rice seasoning), nori (rice seasoning for ochazuke), and other commercially available foods; infant formula; enteral nutrition; foods for special dietary uses; foods with health claims (foods for specified health uses, foods with nutritional function claims, foods with functional claims); and nutritional supplements. Furthermore, the food and beverage composition of this embodiment may be a supplement, for example, a tablet-type supplement. If it is a supplement, the whey protein hydrolysate can be ingested without being affected by other foods in terms of the amount of food consumed and the calories taken per day. 【0053】 The food and beverage composition according to this embodiment can be manufactured by adding the whey protein hydrolysate to the raw materials of ordinary food and beverages, and can be manufactured in the same manner as ordinary food and beverages, except for the addition of the whey protein hydrolysate. The addition of the whey protein hydrolysate may be carried out at any stage in the manufacturing process of the food and beverage composition. 【0054】 The food and beverage composition in this embodiment also includes raw materials for manufacturing the food and beverage composition, and food additives, etc., that are added to the food and beverage composition during or after the manufacturing process. 【0055】 Furthermore, the food and beverage composition of this embodiment may use known or future-discovered prebiotic components or components that support prebiotic effects (hereinafter referred to as "prebiotics"), as long as they do not impair the effects of this embodiment. For example, the food and beverage composition of this embodiment can be manufactured by blending prebiotics such as whey protein, casein protein, soy protein, or pea protein (pea protein) or mixtures thereof, hydrolyzed products; amino acids such as leucine, valine, isoleucine, or glutamine; vitamins such as vitamin B6 or vitamin C; creatine; citric acid; fish oil; or oligosaccharides such as isomaltoligosaccharide, xylooligosaccharide, soy oligosaccharide, fructooligosaccharide, lactulose, etc., with the whey protein hydrolysate. 【0056】 The content of whey protein hydrolysate in the food and beverage composition of this embodiment is set appropriately depending on the embodiment of the food and beverage composition, for example, 5% or more, 10% or more, 20% or more, etc., while on the other hand, it may be 90% or less, 80% or less, 70% or less, etc. A non-inconsistent combination of these may also be acceptable. For example, 5-90%, 10-80%, 20-70%, etc. Furthermore, the content of the whey protein hydrolysate may be the content as a dry product. 【0057】 The proportion of the whey protein hydrolysate in the food and beverage composition of this embodiment may be determined according to the amount of the food and beverage composition consumed by the person in one serving and the amount of the whey protein hydrolysate contained in the food and beverage composition of this embodiment. 【0058】 The intake amount (effective amount) of the food and beverage composition in this embodiment is set appropriately depending on the form of the food and beverage composition, method of use, target, target age, sex, and other conditions, but is not particularly limited as long as the renal function improving effect is exerted in the target who ingests it. For example, the amount of whey protein hydrolysate may be 2g / day or more, 5g / day or more, 8g / day or more, on the other hand, 50g / day or less, 20g / day or less, 12g / day or less, etc. Non-contradictory combinations of these may also be used. For example, 2-50g / day, 5-20g / day, 8-12g / day, etc. The conversion rate per kg of body weight could be, for example, 0.01 g / kg body weight / day or more, 0.05 g / kg body weight / day or more, while on the other hand, it could be 1 g / kg body weight / day or less, 0.5 g / kg body weight / day or less, etc. A non-contradictory combination of these is also acceptable. For example, 0.01 to 1 g / kg body weight / day, 0.05 to 0.5 g / kg body weight / day, etc. Furthermore, the amount of the whey protein hydrolysate may be the amount in dry form. 【0059】 The number of times the food and beverage composition of this embodiment is consumed per day is not particularly limited and can be appropriately determined according to the amount of the whey protein hydrolysate consumed per day. The food and beverage composition of this embodiment is preferably consumed regularly for a certain period of time. The period of consumption is preferably 8 weeks or more, more preferably 10 weeks or more, and even more preferably 12 weeks or more. 【0060】 The food and beverage composition of this embodiment may be taken alone, or together with other food and beverage compositions or foods, or pharmaceutical compositions or pharmaceuticals. For example, it may be taken together with other food and beverage compositions or foods for improving kidney function, or pharmaceutical compositions or pharmaceuticals for improving kidney function. 【0061】 The food and beverage composition according to this embodiment can be sold as a food or beverage composition or food product labeled with the use of improving kidney function, etc. Furthermore, it goes without saying that any other wording that describes a secondary effect resulting from the above-mentioned use can also be used. 【0062】 The term "display" as used herein refers to all actions taken to inform consumers of the above-mentioned uses. Any display that can evoke or evoke the above-mentioned uses falls under the definition of "display" in this embodiment, regardless of the purpose of the display, the content of the display, the object or medium on which it is displayed, etc. However, it is preferable to display the above-mentioned uses in a way that allows consumers to directly recognize them. Specifically, examples include the act of describing the above-mentioned use on food and beverage compositions or products related to food and beverages according to this embodiment, or on the packaging of such products; the act of transferring, delivering, displaying for transfer or delivery, or importing products or products on which the above-mentioned use is described; describing the above-mentioned use on advertisements, price lists, or transaction documents relating to the products and displaying or distributing them; or describing the above-mentioned use on information containing such materials and providing it by electromagnetic means (such as the Internet). In particular, it is preferable to describe the use on promotional materials at sales sites such as packaging, containers, catalogs, brochures, POP displays, and other documents. 【0063】 Furthermore, it is preferable that the display be one authorized by the government or other administrative body (for example, a display that has been approved based on various systems established by the government and is carried out in accordance with such approval). For example, examples include labels such as health functional foods, health foods, functional foods, enteral nutrition foods, foods for special dietary uses, nutrient function foods, and quasi-drugs. Other examples include labels approved by the Consumer Affairs Agency, such as foods for specified health uses, nutrient function foods, foods with functional claims, and labels approved under similar systems. Examples of the latter include labels as foods for specified health uses, labels as conditionally specified health uses, labels indicating an effect on the structure or function of the body, labels indicating a reduction in disease risk, and labels indicating scientifically based functionality. More specifically, examples include labels as foods for specified health uses (especially labels indicating health uses) as defined in the Cabinet Office Ordinance concerning the permission of special use labels as stipulated in the Health Promotion Act (Cabinet Office Ordinance No. 57 of August 31, 2009), and similar labels. 【0064】 Examples of such claims include: "Maintains kidney function," "May contribute to kidney health," "For those with mild kidney dysfunction," "Reduces swelling," "Alleviates anemia," "Reduces fatigue," and "Reduces the inconvenience of urinating." 【0065】 The food and beverage composition of this embodiment can be used for any subject, including healthy and unhealthy individuals. However, if the food or beverage is labeled with a specific use or function, it may be used for the non-therapeutic purposes described above. 【0066】 The pharmaceutical composition of this embodiment is not particularly limited as long as it contains the whey protein hydrolysate. The pharmaceutical composition of this embodiment may use the whey protein hydrolysate as is, or it may be formulated by incorporating a physiologically acceptable liquid or solid pharmaceutical carrier. 【0067】 The dosage form of the pharmaceutical composition in this embodiment is not particularly limited, and specific examples include tablets, pills, powders, liquids, suspensions, emulsions, granules, capsules, syrups, suppositories, injections, ointments, patches, eye drops, and nasal drops. Furthermore, in formulation, additives such as excipients, binders, disintegrants, lubricants, stabilizers, flavoring agents, diluents, surfactants, or solvents for injections, which are commonly used as formulation carriers, can be used. 【0068】 Furthermore, various organic or inorganic carriers can be used as the formulation carrier, depending on the dosage form. Examples of carriers in the case of solid formulations include excipients, binders, disintegrants, lubricants, stabilizers, flavoring agents, and odor-masking agents. 【0069】 Examples of excipients include sugar derivatives such as lactose, sucrose, glucose, mannitol, and sorbitol; starch derivatives such as corn starch, potato starch, α-starch, dextrin, and carboxymethyl starch; cellulose derivatives such as crystalline cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, carboxymethylcellulose, and carboxymethylcellulose calcium; gum arabic; dextran; pullulan; silicate derivatives such as light anhydrous silicic acid, synthetic aluminum silicate, and magnesium aluminometasilicate; phosphate derivatives such as calcium phosphate; carbonate derivatives such as calcium carbonate; and sulfate derivatives such as calcium sulfate. 【0070】 Examples of binders include, in addition to the above-mentioned excipients, gelatin, polyvinylpyrrolidone, macrogol, and the like. 【0071】 Examples of disintegrants include, in addition to the above-mentioned excipients, chemically modified starches or cellulose derivatives such as croscarmellose sodium, carboxymethyl starch sodium, and cross-linked polyvinylpyrrolidone. 【0072】 Examples of lubricants include talc; stearic acid; metal stearate salts such as calcium stearate and magnesium stearate; colloidal silica; beegum; waxes such as gayl wax; boric acid; glycol; carboxylic acids such as fumaric acid and adipic acid; sodium carboxylate salts such as sodium benzoate; sulfates such as sodium sulfate; leucine; lauryl sulfates such as sodium lauryl sulfate and magnesium lauryl sulfate; silicic acids such as anhydrous silicic acid and silicic acid hydrate; and starch derivatives. 【0073】 Examples of stabilizers include para-hydroxybenzoic acid esters such as methylparaben and propylparaben; alcohols such as chlorobutanol, benzyl alcohol, and phenylethyl alcohol; benzalkonium chloride; acetic anhydride; and sorbic acid. 【0074】 Examples of flavoring and odor-modifying agents include sweeteners, acidulants, and flavorings. In the case of liquid formulations for oral administration, examples of carriers used include solvents such as water, and flavoring and odor-masking agents. 【0075】 The content of the whey protein hydrolysate in the pharmaceutical composition of this embodiment is set appropriately depending on the embodiment of the pharmaceutical composition, for example, 5% or more, 10% or more, 20% or more, etc., while on the other hand, it may be 90% or less, 80% or less, 70% or less, etc. A non-inconsistent combination of these may also be acceptable. For example, 5-90%, 10-80%, 20-70%, etc. Furthermore, the content of the whey protein hydrolysate may be the content as a dry product. 【0076】 The proportion of the whey protein hydrolysate in the pharmaceutical composition of this embodiment may be determined according to the amount of the pharmaceutical composition administered to the recipient in one dose and the amount of the whey protein hydrolysate contained in the pharmaceutical composition of this embodiment. 【0077】 The dosage (effective dose) of the pharmaceutical composition in this embodiment is set appropriately depending on the form of the pharmaceutical composition, method of use, target, age, sex, and other conditions of the target, but is not particularly limited as long as the renal function improving effect is exerted in the target to whom it is administered. For example, the amount of whey protein hydrolysate may be 2 g / day or more, 5 g / day or more, 8 g / day or more, etc., while on the other hand, it may be 50 g / day or less, 20 g / day or less, 12 g / day or less, etc. Non-contradictory combinations of these may also be used. For example, 2 to 50 g / day, 5 to 20 g / day, 8 to 12 g / day, etc. The conversion rate per kg of body weight could be, for example, 0.01 g / kg body weight / day or more, 0.05 g / kg body weight / day or more, while on the other hand, it could be 1 g / kg body weight / day or less, 0.5 g / kg body weight / day or less, etc. A non-contradictory combination of these is also acceptable. For example, 0.01 to 1 g / kg body weight / day, 0.05 to 0.5 g / kg body weight / day, etc. Furthermore, the amount of the whey protein hydrolysate may be the amount in dry form. 【0078】 The number of times the pharmaceutical composition of this embodiment is administered per day is not particularly limited and can be appropriately determined according to the daily dose of the whey protein hydrolysate. The pharmaceutical composition of this embodiment is preferably administered continuously for a certain period of time. The administration period is preferably 8 weeks or more, more preferably 10 weeks or more, and even more preferably 12 weeks or more. 【0079】 The pharmaceutical composition according to this embodiment may be administered to non-healthy individuals for the therapeutic purpose of treating diseases that can be prevented or treated by improving renal function. Furthermore, the pharmaceutical composition according to this embodiment may be administered to healthy individuals for the non-therapeutic purpose of preventing diseases that can be prevented or treated by improving renal function. 【0080】 The pharmaceutical composition of this embodiment may be administered alone or in combination with other pharmaceutical compositions or pharmaceuticals, or food and beverage compositions or foods. For example, it may be administered in combination with other pharmaceutical compositions or pharmaceuticals for improving renal function, or food and beverage compositions or foods for improving renal function, etc. 【0081】 In addition to the embodiments described herein, this disclosure may also provide, for example, the following embodiments: Use of whey protein hydrolysates having the physicochemical properties of (1) to (3) above for the production of a composition for improving renal function. Use of whey protein hydrolysates having the physicochemical properties described in (1) to (3) above to improve kidney function. Use of a composition containing a whey protein hydrolysate having the physicochemical properties of (1) to (3) described above, for the purpose of improving kidney function. Non-therapeutic use of whey protein hydrolysates having the physicochemical properties of (1) to (3) described above to improve renal function. Non-therapeutic use of a composition containing a whey protein hydrolysate having the physicochemical properties of (1) to (3) described above, for the purpose of improving renal function. A whey protein hydrolysate having the physicochemical properties of (1) to (3) described above, for use in improving renal function. A composition containing a whey protein hydrolysate having the physicochemical properties of (1) to (3) described above, for use in improving renal function. A method for improving renal function, comprising administering an effective amount of a whey protein hydrolysate having the physicochemical properties of (1) to (3) described above to a subject requiring improvement. A method for improving renal function, comprising administering an effective amount of a composition containing a whey protein hydrolysate having the physicochemical properties of (1) to (3) above to a subject requiring improvement. [Examples] 【0082】 The present disclosure will be further described below using examples, but the present disclosure is not limited to these examples. 【0083】 [Test Example 1] (1) Preparation of test samples A commercially available whey protein concentrate (WPC, Milei80, manufactured by Mirai Co., Ltd.) was dissolved in water at a concentration of 10%, and sodium hydroxide was added to adjust the pH of the solution to 8.0 to prepare a whey protein aqueous solution. To this whey protein aqueous solution, 5,000 units of protease N Amano (manufactured by Amano Enzyme Co., Ltd.) were added per gram of protein, and the solution was decomposed at 50°C for 7 hours at pH 8.0. Next, the enzyme was inactivated by heating at 90°C for 10 minutes, and the solution was powdered using a spray dryer to obtain a dried whey protein hydrolysate. The dried whey protein hydrolysate produced in this manner was then individually packaged in 5g portions. In this study, Milei80 (manufactured by Mirai Co., Ltd.) was used as the WPC. Generally, WPC (whey protein concentrate) contains 15-25% α-lactalbumin, 50-65% β-lactoglobulin, 5-10% bovine serum albumin, lactoferrin, etc. 【0084】 The physicochemical properties of the obtained whey protein hydrolysate were as follows: 1) The average molecular chain length of whey protein hydrolysate was 3-5. The average molecular chain length was measured by the TNBS method (described in "3) Average Peptide Chain Length Measurement Method: TNBS Method" in "Journal of the Japanese Society of Nutrition and Food Science, Vol. 47, No. 3, 195-201 (1994)"). 2) The fraction of whey protein hydrolysate with a molecular weight of 5,000 to 10,000 daltons accounted for less than 2% of the total whey protein hydrolysate. The percentage within each fraction was measured using the method described in <Measurement of Molecular Weight Distribution> above. 3) The amount of free amino acids relative to the total amount of amino acids in the whey protein hydrolysate was 6% or less. The amount of free amino acids contained in the whey protein hydrolysate was measured using the formula: Percentage of total mass of free amino acids (%) = (Mass of total free amino acids / Mass of total amino acids) × 100 (see <Method for calculating amino acid free rate> described in Japanese Patent Publication No. 2017-31105). 4) The transmittance of the 10% by mass whey protein hydrolysate solution was measured using a spectrophotometer (U-2000, Hitachi, Ltd.: 540 nm), and the transmittance at 540 nm for the 10% by mass whey protein hydrolysate solution was 97% or higher. 5) When a 5% by mass whey protein hydrolysate solution (pH 4-7) was heated at 120°C for 10 minutes, the presence or absence of precipitate was visually checked, but no precipitate was observed. 6) When a 5% by mass whey protein hydrolysate solution was heated at 85°C for 10 minutes at pH 3-5 in the presence of 0.025 mol / L calcium chloride, the presence or absence of gelation was visually confirmed, but no gelation occurred. 【0085】 (2) Administration study Fifty-two adult males without chronic diseases were selected as subjects. These subjects were divided into two groups: a test group of 25 subjects who ingested the whey protein hydrolysate prepared in "(1) Preparation of Test Samples" (2 subjects with GFR classification G1, 17 subjects with GFR classification G2, 6 subjects with GFR classification G3a, and 0 subjects with GFR classification G3b), and a control group of 27 subjects who ingested the control product (2 subjects with GFR classification G1, 20 subjects with GFR classification G2, 4 subjects with GFR classification G3a, and 1 subject with GFR classification G3b). The test group was given a 5g packet of the dried whey protein hydrolysate prepared in "(1) Preparation of Test Samples" above, dissolved in 100mL of drinking water, once a day for 12 weeks. The control group, on the other hand, was given a sample containing 5g of dextrin (manufactured by Matsutani Chemical Industry Co., Ltd.) per packet, dissolved in 100mL of drinking water, once a day for 12 weeks as a control. Blood samples were collected from subjects before each sample intake (week 0) and after the final intake (week 12), and serum creatinine levels were measured. Estimated glomerular filtration rate (eGFR) was calculated using these measurements along with age. Statistical significance of serum creatinine levels and eGFR between pre-intake (week 0) and post-intake (week 12) was examined using t-tests, and the values ​​for both the test group and the control group after intake (week 12) were examined using ANCOVA to verify statistical significance. 【0086】 (3) Results The blood creatinine levels and eGFR of the subjects in each group are as shown in the table below. ** This indicates a significant improvement (p<0.01) compared to week 0. P† indicates a significant difference between the test group and the control group after intake (week 12). In the test group, the mean blood creatinine level decreased by 0.03 mg / dL after intake (week 12) compared to before intake (week 0). On the other hand, in the control group, there was no change in the mean blood creatinine level after intake (week 12) compared to before intake (week 0). Furthermore, based on this, when eGFR was calculated, the mean eGFR in the test group was 2 mL / min / 1.73 m² after intake (week 12) compared to before intake (week 0). 2 The above increase was observed. On the other hand, in the control group, the eGFR (mean value) after intake (week 12) was 0.5 mL / min / 1.73 m² compared to before intake (week 0). 2 The decrease was as follows: 【0087】 [Table 1] 【0088】 These results clearly show that consuming the whey protein hydrolysate prepared in "(1) Preparation of Test Samples" over a long period of 12 weeks or more significantly reduces blood creatinine levels and significantly increases eGFR. In other words, this whey protein hydrolysate can be used as an active ingredient in compositions for improving renal function. Furthermore, this whey protein hydrolysate can be effectively used to prevent chronic kidney disease (CKD). In other words, because the whey protein hydrolysate has a renal function-improving effect, it can effectively improve blood creatinine levels and eGFR that have worsened due to, for example, the intake of food and beverages, and is also effective in preventing, for example, chronic kidney disease (CKD) caused by the intake of food and beverages. Furthermore, the whey protein hydrolysate has excellent processing stability, low bitterness, and a good flavor, making it safe for continuous consumption. Therefore, according to this disclosure, it is possible to provide a renal function improving composition that has excellent renal function improving effects, a good flavor, and is easy to drink, such as a pharmaceutical composition or a food and beverage composition for improving renal function.

Claims

[Claim 1] A composition for improving renal function, comprising a whey protein hydrolysate having the following physicochemical properties (1) to (3). (1) The average molecular chain length of whey protein hydrolysates is 2 to 10. (2) The fraction of whey protein hydrolysate with a molecular weight of 5,000 to 10,000 daltons accounts for 8% or less of the total whey protein hydrolysate. (3) The amount of free amino acids relative to the total amount of amino acids in the whey protein hydrolysate is 10% or less. [Claim 2] The composition according to claim 1, which reduces blood creatinine levels and / or increases estimated glomerular filtration rate. [Claim 3] The composition according to claim 1, which is used for a subject whose GFR classification is G2, and / or a subject whose GFR classification is G3. [Claim 4] The composition according to claim 3, wherein the subject whose GFR classification is G3 is the subject whose GFR classification is G3a. [Claim 5] A food and beverage composition according to any one of claims 1 to 4. [Claim 6] A pharmaceutical composition, as described in any one of claims 1 to 4.

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