Composition for lowering blood pressure and / or reducing neutral fat

Abstract

To provide a composition for lowering blood pressure and / or lowering neutral fat, which has few side effects and is highly safe. [Solution] A composition for lowering blood pressure and / or reducing neutral fat, comprising a casein hydrolysate and indigestible dextrin; preferably, the casein hydrolysate comprises a peptide consisting of Met-Lys-Pro; preferably, the casein hydrolysate comprises a peptide consisting of Met-Lys-Pro, and the indigestible dextrin is present in an amount of 5,000 to 100,000 parts by mass per part by mass of the peptide.

Description

[Technical field]

[0001] The present technology relates to compositions for lowering blood pressure and / or lowering neutral fats. [Background technology]

[0002] Since lifestyle-related diseases are a factor that impedes healthy longevity, the government and medical institutions encourage people with lifestyle-related diseases and those at risk to improve their lifestyles. These lifestyle-related diseases are classified into a wide range of categories, including hypertension, dyslipidemia, and diabetes. Hypertension puts strong pressure on the walls of blood vessels, damaging them and accelerating the aging process, and also adversely affects the entire body (especially the kidneys, brain, retina, etc.). Dyslipidemia also damages the inside of blood vessels due to LDL cholesterol and neutral fats (triglycerides) in the blood, gradually leading to arteriosclerosis. Although neither hypertension nor dyslipidemia has distinctive symptoms, if they manifest as events, they may lead to death, and these events may also cause a decrease in quality of life (QOL).

[0003] For this reason, hypertensive patients, dyslipidemia patients, or potential patients (so-called borderline patients) need to administer or take substances that lower blood pressure, or substances that reduce blood triglycerides and LDL cholesterol. Usually, these people need to administer or take active ingredients for a long period of time to maintain the lowered state of blood pressure and blood triglycerides, etc., so it is desirable for active ingredients to be safe even when taken for as long a period as possible. In addition, from the viewpoint of preventing onset, some people want to take them every day from when their levels are slightly higher than the standard values, so active ingredients with high safety are desirable.

[0004] For example, Patent Document 1 discloses that resistant dextrin is said to have the same effect as ingesting dietary fiber, and has the effect of slowing down the rapid rise in blood glucose, insulin, or triglyceride levels after a meal. However, there are those who strongly desire active ingredients that have fewer side effects, are highly safe, and have better blood pressure lowering and / or neutral fat lowering effects. [Prior art documents] [Patent documents]

[0005] [Patent Document 1] JP 2001-252064 A Summary of the Invention [Problem to be solved by the invention]

[0006] Therefore, a main object of the present technology is to provide a composition for lowering blood pressure and / or lowering neutral fat, which has few side effects and is highly safe. [Means for solving the problem]

[0007] In order to solve the above problems, the present inventors have conducted extensive research into the search for a substance that has few side effects and is highly safe, and exhibits a blood pressure lowering effect and / or a neutral fat lowering effect. It is known that resistant dextrin inhibits the absorption of ingredients in the intestine by absorbing water and becoming a sticky gel. Therefore, the present inventors believed that it would be difficult to obtain the expected blood pressure lowering effect and / or neutral fat lowering effect even if resistant dextrin was taken in combination with other ingredients for a long period of time. However, the inventors discovered in a model rat test that combined intake of a mixture of casein hydrolysate and resistant dextrin exerted excellent blood pressure lowering and triglyceride reducing effects, leading to the completion of the present invention.

[0008] That is, the present technology is as follows. [1] A composition for lowering blood pressure and / or reducing neutral fats, comprising casein hydrolysate and resistant dextrin. [2] The composition described in [1] above, wherein the casein hydrolysate contains a peptide consisting of Met-Lys-Pro. [3] The composition according to [1] or [2] above, wherein the resistant dextrin and the casein hydrolysate are contained in a mass ratio of 10:0.001 to 1:1. [4] The composition according to any one of [1] to [3] above, wherein the casein hydrolysate contains a peptide consisting of Met-Lys-Pro, and the amount of resistant dextrin is 5,000 to 100,000 parts by mass per part by mass of the peptide. [5] The composition according to any one of the above [1] to [4], which is a pharmaceutical composition or a food or drink composition. [6] The composition according to [5] above, which is used for lowering blood pressure and / or reducing neutral fats. [7] The composition according to [5] or [6] above, which is used for the prevention or treatment of hypertension and / or dyslipidemia. [8] The composition according to any one of [1] to [5] above, wherein the composition is a fermented food or drink. [9] The composition according to any one of the above [1] to [6], which is in a unit package form. The technology also provides the following: <1> A composition for lowering blood pressure and suppressing an increase in neutral fat, comprising a casein hydrolysate and a resistant dextrin, The casein hydrolysate contains a peptide consisting of Met-Lys-Pro, The composition is used so that the amount of the resistant dextrin used by a subject who ingests the composition is 0.01 to 1 g / kg body weight / day, The content of the peptide in the composition is 1 part by mass per 5,000 to 100,000 parts by mass of the indigestible dextrin. The composition. <2> The suppression of an increase in neutral fat is the suppression of an increase in neutral fat within 6 hours after a meal that includes ingestion of the composition. <1> The composition described in <3> The composition is used for lowering blood pressure and suppressing an increase in neutral fat within 6 hours after a meal that includes ingestion of the composition. <1> The composition described in <4> The composition is in the form of a powder, granules, tablet, or capsule. <1> ~ <3> 13. The composition according to any one of claims 1 to 12. <5> The composition is a fermented food or drink. <1> ~ <3> 13. The composition according to any one of claims 1 to 12. <6> The composition is a pharmaceutical composition or a food or beverage composition. <1> ~ <3> 13. The composition according to any one of claims 1 to 12. <7> The composition is a composition for lowering blood pressure, suppressing an increase in neutral fat, and suppressing an increase in postprandial blood glucose. <1> ~ <6> 13. The composition according to any one of claims 1 to 12. Effect of the Invention

[0009] According to the present technology, it is possible to provide a composition for lowering blood pressure and / or lowering neutral fat, which has few side effects and is highly safe. Note that the effects described herein are not necessarily limited, and may be any of the effects described in the present technology. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0010] A preferred embodiment for carrying out the present technology will be described below. Note that the embodiment described below shows an example of a typical embodiment of the present disclosure, and the scope of the present technology is not narrowly interpreted by this. Note that in this specification, when a numerical range is expressed as "lower limit to upper limit", the upper limit may be "less than" or "less than", and the lower limit may be "more than" or "greater than". In addition, in this specification, percentages are expressed by mass unless otherwise specified.

[0011] The present technology can exert a blood pressure lowering effect and / or a neutral fat lowering effect by using a casein hydrolysate and a resistant dextrin in combination. The present technology is a composition for lowering blood pressure and / or lowering neutral fat that contains a casein hydrolysate and a resistant dextrin as active ingredients, and the composition can be suitably used in a pharmaceutical composition or a food and drink composition (more suitably fermented milk).

[0012] 1. Casein hydrolysate The casein hydrolysate used in the present technology is obtained by hydrolyzing milk-derived casein protein, and contains various decomposed components derived from casein protein. In order to better exert the efficacy of the present technology, it is preferable that the casein hydrolysate contains at least a peptide consisting of Met-Lys-Pro (Sequence No. 1) (hereinafter also referred to as "tripeptide MKP"). The tripeptide MKP of the present technology is known to have angiotensin-converting enzyme inhibitory activity, dipeptidyl peptidase-IV inhibitory activity, and the like (e.g., Reference 1 (WO2003 / 044044), Reference 2 (WO2013 / 125622), Reference 3 (JP Patent Publication No. 2016-069343), etc.).

[0013] It is preferable that the casein hydrolysate contains the tripeptide MKP and is further subjected to a combination of one or more conditions selected from the following (a), (b), and (c): (a) the average molecular weight of the casein hydrolysate is 1,200 daltons or less; (b) the hydrolysis rate of the casein hydrolysate is 20 to 30%; (c) the mass ratio of free amino acids to the total mass of all amino acids contained in the casein hydrolysate is 10 mass% or less.

[0014] The content of the tripeptide MKP in the casein hydrolysate is not particularly limited, but the lower limit is preferably 0.001% by mass or more, more preferably 0.005% by mass or more, and even more preferably 0.01% by mass or more from the viewpoint of better exerting the efficacy of the present technology, and the upper limit is preferably 1% by mass or less, more preferably 0.5% by mass or less, even more preferably 0.2% by mass or less, and even more preferably 0.1% by mass or less from the viewpoint of the production efficiency of the hydrolysate of the present technology. The content of the tripeptide MKP is more preferably 0.001 to 1% by mass, even more preferably 0.005 to 0.5% by mass, and even more preferably 0.01 to 0.1% by mass. The (a), (b) and (c) in the casein hydrolysate are preferably within the ranges prepared by the "(2) Method for producing casein hydrolysate" described below.

[0015] The method for producing the casein hydrolysate used in the present technology will be described in detail below. (1) Raw materials The raw material casein is mainly composed of milk-derived protein, and the casein is not particularly limited, but for example, various commercially available caseins, caseinates, etc. can be used. More specifically, casein lactate, casein sulfate, casein hydrochloride, sodium caseinate, potassium caseinate, calcium caseinate, magnesium caseinate, or any mixture thereof can be used. In addition, casein purified from cow's milk, skim milk, whole milk powder, skim milk powder by a conventional method, etc. can also be used.

[0016] Casein hydrolysate, the active ingredient of this technology, is produced by hydrolyzing casein, a relatively inexpensive milk-derived raw material used as a biomaterial, and can therefore be produced stably, easily, and in large quantities.

[0017] (2) Method for producing casein hydrolysate The method for producing casein hydrolysate is not particularly limited, but examples include a method using an acid or alkali, a method using an enzyme such as a protease, etc. Among these, the method using an enzyme is preferable because it allows the desired peptides, etc. to be contained. A method for producing a casein hydrolysate using a protease will be specifically described below.

[0018] First, the raw material (casein) is dispersed and dissolved in water. The concentration of the dissolving solution is not particularly limited, but is usually preferably in the range of about 5 to 15 mass % in terms of protein from the standpoint of efficiency and operability.

[0019] Next, the pH of the dissolution solution is adjusted to about the optimum pH of the protease to be used to prepare a raw material aqueous solution. Specifically, the pH of the dissolution solution is preferably adjusted to pH 7 to 10 using an alkaline solution, which is within the optimum pH range of many proteases. The alkaline agent used for adjusting the pH is not particularly limited, but examples thereof include sodium hydroxide, potassium hydroxide, potassium carbonate, and the like.

[0020] Next, a protease is added to the prepared raw material aqueous solution. The protease may be derived from bacteria, animals, or plants, and any of these may be used.

[0021] The bacterial proteolytic enzyme is not particularly limited, and examples thereof include endoproteases derived from the genus Bacillus, such as Alcalase (manufactured by Novozymes), Neutrase (manufactured by Novozymes), Protin A (manufactured by Yamato Chemical Industry Co., Ltd.), Protin P (manufactured by Yamato Chemical Industry Co., Ltd.), Proleather (manufactured by Amano Enzyme Co., Ltd.), Protease N (manufactured by Amano Enzyme Co., Ltd.), Corolase 7089 (manufactured by Higuchi Shokai), Bioprase (manufactured by Nagase Chemtec Corporation), Orientase 90N (manufactured by HIBI), and Orientase 22BF (manufactured by HIBI). The animal-derived proteolytic enzyme is not particularly limited, but examples thereof include PTN (manufactured by Novozymes), which contains trypsin as a main component, and Trypsin V (manufactured by Japan Biocon Co., Ltd.). The plant-derived proteolytic enzyme is not particularly limited, but examples thereof include papain (manufactured by Amano Enzyme Inc.) and bromelain (manufactured by Amano Enzyme Inc.). The above-mentioned proteases can be used alone or in combination of two or more kinds.

[0022] The protease is preferably used by dispersing and dissolving it in cold water at 4 to 10° C. The concentration of the protease in the solution is not particularly limited, but it is usually desirable to use the protease in an amount that results in an enzyme concentration of about 3 to 10% in terms of efficiency and operability.

[0023] The amount of proteolytic enzyme used for casein hydrolysis varies depending on the substrate concentration, enzyme titer, reaction temperature, reaction time, etc., but generally, a desirable amount is 1,000 to 20,000 units (activity units) per gram of casein protein equivalent mass.

[0024] The activity unit of a protease can be measured depending on the type of protease used.

[0025] When adding the protease, it is preferable to dissolve and add each type one at a time, but the order of addition is not particularly limited.

[0026] During the enzyme reaction, the temperature of the reaction system is not particularly limited and is selected from a practical range including the optimum temperature range for the expression of the enzyme activity, and is usually selected from the range of 30 to 60°C. The reaction duration varies depending on reaction conditions such as reaction temperature and initial pH, and it can be difficult to determine the reaction duration in general because, for example, if the reaction duration of an enzyme reaction is constant, there is a possibility that hydrolyzates having different physicochemical properties may be generated for each production batch. Therefore, it is desirable to monitor the enzyme reaction and determine the reaction duration so that the physicochemical properties of the casein hydrolysate become the desired values. The enzyme reaction can be monitored, for example, by sampling a portion of the reaction solution and measuring the protein decomposition rate, etc.

[0027] The enzymatic reaction is then stopped. The enzymatic reaction is stopped by inactivating the enzyme in the hydrolyzed solution, which can be carried out by a conventional method such as heat inactivation. The conditions for the heat inactivation treatment (heating temperature, heating time, etc.) can be appropriately set taking into account the thermal stability of the enzyme used so as to ensure sufficient inactivation. For example, the treatment can be performed at a temperature range of 80 to 130°C for a holding time of 30 minutes to 2 seconds.

[0028] After the enzyme reaction is stopped, the resulting hydrolysis-inactivated liquid is preferably purified by any one or a combination of two or more selected from the group consisting of (1) filtration, (2) membrane separation treatments such as microfiltration and ultrafiltration membranes, and (3) resin adsorption separation.

[0029] By carrying out the above-mentioned purification, it is possible to remove insoluble matters contained in the inactivated liquid, reduce fat, lactose, and other unnecessary components, etc. As a result, it is possible to obtain a casein hydrolysate that is transparent in a solution state and does not cause turbidity, precipitation, aggregation, browning, etc. even when stored in a solution state for a long period of time, i.e., has excellent storage stability.

[0030] Furthermore, by carrying out the above-mentioned purification, the flavor, appearance, etc. of the casein hydrolysate used in the present technology can be improved.

[0031] The filtration (1) above can be carried out by a known method, for example, by using diatomaceous earth and a known device. By carrying out filtration, insoluble matters that are present in the hydrolysis-inactivated liquid and that have been produced during the hydrolysis reaction and / or during the enzyme heat-inactivation can be removed.

[0032] The membrane separation treatment of (2) above can be carried out using a known device, which is not particularly limited, and examples thereof include a microfiltration module, ultrafiltration module SEP1053 (manufactured by Asahi Kasei Corporation, molecular weight cutoff 3,000), SIP1053 (manufactured by Asahi Kasei Corporation, molecular weight cutoff 6,000), and SLP1053 (manufactured by Asahi Kasei Corporation, molecular weight cutoff 10,000). In this case, a solution containing casein hydrolysate is obtained as a membrane permeant fraction after membrane separation treatment. By carrying out the membrane separation treatment, insoluble matters produced during the hydrolysis reaction and / or during the enzyme heat inactivation and present in the hydrolysis-inactivated liquid can be removed, as in the filtration in (1) above.

[0033] The resin adsorption separation in (3) above can be carried out by a known method, for example, by filling a column with a resin and passing the hydrolysis deactivation liquid through the column. The resin is not particularly limited, but examples thereof include trade names such as Diaion, Sepabeads (manufactured by Mitsubishi Chemical Corporation), Amberlite XAD (manufactured by Organo Corporation), and KS-35 (manufactured by Ajinomoto Fine-Techno Co., Ltd.). The resin adsorption separation can be carried out in a continuous manner by filling a column with the resin and continuously injecting and discharging the hydrolysis and deactivation liquid into and from the column, or in a batch manner by introducing the resin into the hydrolysis and deactivation liquid and allowing the resin to come into contact with the hydrolysis and deactivation liquid for a certain period of time, followed by separating the hydrolysis and deactivation liquid from the resin. The hydrolysis inactivated solution may contain factors that cause turbidity, precipitation, aggregation, browning, etc. during storage (e.g., peptides containing a large amount of hydrophobic amino acids), and these factors can be removed by performing resin adsorption separation.

[0034] After purification, the resulting solution containing the casein hydrolysate may also be sterilized. The sterilization method may be a conventional heat treatment method or the like. The heating temperature and holding time during the heat treatment may be appropriately set so as to achieve sterilization. For example, sterilization can be achieved by heat treatment at 70 to 140° C. for 2 seconds to 30 minutes. The heat sterilization method may be either a batch method or a continuous method, and in the continuous method, methods such as a plate heat exchange method, an infusion method, and an injection method can be used.

[0035] The obtained solution containing the casein hydrolysate can be used as it is, or, if necessary, the solution can be concentrated by a known method to be used as a concentrate. The concentrate can also be dried by a known method to be used as a powder.

[0036] In addition, after removing the insoluble components from the casein hydrolysate, a secondary hydrolysis may be carried out by adding an endoprotease or an exoprotease for the purpose of improving flavor or physical properties.

[0037] In addition, after removing the insoluble components from the casein hydrolysate, a secondary hydrolysis may be carried out by adding an endoprotease or an exoprotease for the purpose of improving flavor or physical properties.

[0038] Here, in order to achieve better efficacy of the present technology, it is preferable to prepare the casein hydrolysate to have an average molecular weight of preferably 1200 daltons or less, more preferably 1000 daltons or less, even more preferably 800 daltons or less, and even more preferably 450 daltons or less. It is more preferable to prepare the casein hydrolysate to have an average molecular weight of more preferably 250 to 450 daltons, and even more preferably 360 to 390 daltons. Furthermore, from the viewpoint of exerting better efficacy of the present technology, it is preferable to prepare the casein hydrolysate to have a hydrolysis rate of preferably 10% or more at the upper limit and 40% or less at the lower limit, and even more preferably 20 to 30%. In the present technology, it is preferable to determine the reaction conditions, such as the reaction temperature and reaction duration, so that the degree of hydrolysis is such that the average molecular weight of the casein hydrolysate contained in the filtrate after removing insoluble matter generated during hydrolysis by filtration falls within a target range, and / or the decomposition rate falls within a target range.

[0039] Furthermore, from the viewpoint of exerting a better efficacy of the present technology, it is more preferable to prepare the casein hydrolysate used in the present technology so that the proportion of the total mass of free amino acids to the total mass of all amino acids contained therein is preferably 15% by mass or less, more preferably 10% by mass or less. Furthermore, from the viewpoints of efficacy and production efficiency, the casein hydrolysate used in the present technology is preferably prepared so that the proportion of the tripeptide MKP contained therein is preferably 0.001 to 1 mass%, more preferably 0.005 to 0.5 mass%, and even more preferably 0.01 to 0.1 mass%. In the present technology, the ratio of the total mass of free amino acids or the ratio of tripeptide MKP can be adjusted to the desired ratio by adjusting the type of enzyme used to hydrolyze casein, the amount of enzyme added, the reaction time, and / or the purification conditions after hydrolysis (membrane separation, resin adsorption separation), etc.

[0040] The following describes the <amino acid decomposition rate>, <method of calculating average molecular weight>, <method of calculating amino acid release rate>, and <measurement of tripeptide MKP content> in the casein hydrolysate of the present technology.

[0041] <How to calculate molecular weight> The average molecular weight (Da: Daltons) of the casein hydrolysate in this technology is determined based on the following concept of number average molecular weight. The number average molecular weight, as described in, for example, the literature ("Basics of Polymer Science," edited by the Society of Polymer Science, pp. 116-119, Tokyo Kagaku Dojin Co., Ltd., 1978), indicates the average value of the molecular weight of a polymer compound based on different indices as follows: That is, since polymeric compounds such as protein hydrolysates are heterogeneous substances and have a distribution in molecular weight, the molecular weight of a protein hydrolysate must be expressed as an average molecular weight in order to handle it physicochemically. The number average molecular weight (hereinafter sometimes abbreviated as Mn) is the average for the number of molecules, and is defined by the following mathematical formula (1), where Mi is the molecular weight of peptide chain i and Ni is the number of molecules.

[0042]

number

[0043] <Calculation method for decomposition rate> The decomposition rate of casein hydrolysate can be calculated using the following formula (2).

[0044]

number

[0045] <Calculation method for amino acid release rate> In the present technology, the proportion of the total mass of free amino acids can be determined, for example, by the following procedure.

[0046] (a) Amino acid composition measurement For amino acids other than tryptophan, cysteine, and methionine, the sample is hydrolyzed with 6N hydrochloric acid at 110°C for 24 hours, tryptophan is subjected to alkaline hydrolysis with barium hydroxide at 110°C for 22 hours, and cysteine ​​and methionine are treated with performic acid and then hydrolyzed with 6N hydrochloric acid at 110°C for 18 hours. Each is analyzed using an amino acid analyzer (Hitachi, Model 835) and the masses of the amino acids are measured. In this method, the amounts of glutamine and glutamic acid in a sample are quantified as the glutamic acid analysis value, which is the total amount of both.

[0047] (b) Calculation of the total mass percentage of free amino acids The composition of each amino acid in the sample is measured by the method for measuring amino acid composition (a) above, and the mass of the total amino acids in the sample is calculated by adding them up. The sample is then deproteinized with sulfosalicylic acid, and the mass of each remaining free amino acid is measured by the method (a) above, and the mass of the total free amino acids in the sample is calculated by adding them up. From these values, the ratio of the total mass of the free amino acids in the sample is calculated by the following formula (3).

[0048]

number

[0049] <Measurement of Tripeptide MKP Content> (a) The sample powder is diluted and dissolved in 0.2% formic acid aqueous solution to a concentration of 1.0 mg / mL, and then ultrasonically crushed for 10 minutes, filtered through a 0.22 μm PVDF filter (Millipore) to prepare a powder solution, and LC / MS analysis is performed under the following measurement conditions. Meanwhile, solutions of chemically synthesized standard peptides of the tripeptide MKP (Peptide Institute) are prepared at several concentrations, and LC / MS analysis is performed under the following measurement conditions to create a calibration curve. Among the peaks in the analysis of the powder solution, those that have the same molecular weight and retention time as the standard peptide are identified as having the same sequence as the standard peptide. The content of the tripeptide MKP in the powder solution is determined by comparing the peak area of ​​the standard peptide with the peak area of ​​the sample powder.

[0050] (b) MKP content (mg / g casein hydrolysate) MKP content (mg / g of casein hydrolysate) = [measured tripeptide MKP content (mg) in the obtained casein hydrolysate] / [mass (g) of the obtained casein hydrolysate] [Measured amount (mg) of tripeptide MKP in the obtained casein hydrolysate] is the measured amount of tripeptide MKP in the sample by "LC / MS" described below.

[0051] (c) LC / MS equipment Mass spectrometer: TSQ Quantum Discovery MAX (Thermo Fisher Scientific). High performance liquid chromatograph: Prominence (Shimadzu Corporation), column: XBridge BEH300 C18 φ2.1 mm×250 mm, 3.5 μm (Waters Corporation).

[0052] (d) LC / MS measurement conditions Mobile phase A: 0.2 wt% formic acid-water solution Mobile phase B: 0.2% by weight formic acid-acetonitrile solution Time program: 2%B (0.0 min)-25%B (5.0 min)-65%B (5.1 min)-65%B (10 min)-85%B (10.1 min)-85%B (13.0%)-2%B (13.1 min)-STOP (30.0 min). Sample injection volume: 10 μL, column temperature: 40°C, liquid flow rate: 200 μL / min Analysis mode: SRM measurement. Product Mass: m / z=260.10(Parent m / z = 375.21)

[0053] 2. Resistant dextrin The resistant dextrin used in the present technology is a type of water-soluble dietary fiber obtained from starch, and may be obtained, for example, by enzymatically digesting roasted dextrin, or may be obtained by enzymatically digesting roasted dextrin and then hydrogenating the resulting product. The resistant dextrin of the present technology is a water-soluble dietary fiber that is obtained by adding acid (e.g., adding hydrochloric acid) and / or heating starch derived from plants such as corn, wheat, rice, beans, potatoes, and tapioca, and then enzymatically treating the roasted dextrin with α-amylase and / or glucoamylase as necessary, and then desalting and decolorizing as necessary, and has the characteristic of being resistant to digestion. Such resistant dextrin includes dextrin containing resistant components measured by high performance liquid chromatography (enzyme-HPLC method), which is a dietary fiber analysis method described in Eishin No. 13 dated April 26, 1999 ("Regarding the analysis method of nutritional components, etc. in the nutrition labeling standard"), preferably dextrin containing 85 to 95% by weight of resistant components. For convenience, the resistant dextrin used in the present invention also includes reduced products of resistant dextrin produced by hydrogenation. Resistant dextrin and its reduced product (reduced resistant dextrin) are commercially available in the form of powder, fine particles, granules, etc., and any of these forms can be used in the present technology. In this specification, the term "resistant to digestion" in resistant dextrin means that it is difficult to digest with human digestive enzymes. Resistant dextrin can be quantified by high performance liquid chromatography (enzyme-HPLC method (AOAC2001.03)) (see, for example, Reference 4 (JP Patent Publication 2001-252064 A, Reference 5 (Indigestible Fractions of Starch Hydrolysates and Their Determination Method, Kazuhiro Okuma and Isao Matsuda, J. Appl. Glycosci., Vol. 49 No. 4 p479-485 (2002)), Reference 6 (Thermal Denaturation of Starch and Enzyme Action - Characteristics of Resistant Dextrin -, Kazuhiro Okuma, Isao Matsuda, Yasuo Katsuta, Takao Hanno, Denpun Kagaku Vol. 37 No. 2 p107-114 (1990)), Reference 7 (Preparation of Resistant Dextrin from Roasted Dextrin, Kazuhiro Okuma, Isao Matsuda, J. Appl. Glycosci., Vol. 10, No. 1, p107-114 (1990))). Glycosci., Vol.50 No.3 p389-394(2003)).

[0054] Resistant dextrin is a low-calorie, low-fat food material that is said to have physiologically active effects such as intestinal regulation, suppression of blood sugar rise, serum cholesterol reduction, improvement of the intestinal environment, and neutral fat reduction (e.g., Reference 8 (JP Patent Publication No. 2001-252064), Reference 9 (H04-91765), etc.). For example, references 8 and 9 can be referred to for the method for producing resistant dextrin according to the present invention. The starch used as the raw material for resistant dextrin is not particularly limited, and starches such as corn, potato, sweet potato, tapioca, wheat, barley, and rice can be used, among which corn starch is preferred. In addition, examples of mineral acids used for acidification include hydrochloric acid, nitric acid, and sulfuric acid, among which hydrochloric acid is preferred.

[0055] 3. Uses of casein hydrolysate and resistant dextrin produced by this technology As shown in the Examples below, the casein hydrolysate and resistant dextrin of the present technology have a blood pressure lowering effect and / or a neutral fat reducing effect when used in combination, and can therefore be used to prevent, improve, or treat hypertension and / or dyslipidemia (hyperlipidemia). Furthermore, the casein hydrolysate and resistant dextrin of the present technology are effective for those who have these diseases or symptoms or those at risk of developing them. The present technology can be used to prevent, improve, or treat arteriosclerosis, the symptoms of which tend to progress due to complications of hypertension and dyslipidemia, in particular.

[0056] In general, diuretics used as drugs for lowering blood pressure are said to have the potential to cause hyperglycemia, and there are reports that transglycosylated hesperidin, which has been reported to have a blood neutral fat reducing effect, has not been shown to have any effect on postprandial blood glucose levels. However, in Reference 10 (JP Patent Publication No. 2017-31105), it has been reported that the combined use of casein hydrolysate and resistant dextrin has the potential to suppress postprandial blood glucose rise. That is, although conventional reports have shown that blood pressure lowering compositions or neutral fat reducing compositions may have a risk of hyperglycemia or may not suppress blood glucose rise, the casein hydrolysate and resistant dextrin of the present technology have a low risk of causing hyperglycemia, and can provide an excellent blood pressure lowering and / or neutral fat lowering composition with unprecedented synergistic effects that combine the three elements of blood pressure lowering, neutral fat lowering, and postprandial blood glucose rise suppression. The present technology can provide a blood pressure lowering and / or neutral fat lowering composition or formulation with a reduced risk of side effects for patients with hypertension or dyslipidemia.

[0057] Therefore, the casein hydrolysate and resistant dextrin of the present technology can be contained as active ingredients in compositions or preparations for lowering blood pressure and / or reducing neutral fats, for hypertension and / or dyslipidemia (hyperlipidemia), and can be used for various purposes such as pharmaceuticals, food and beverages, feed, etc., or may be materials or preparations that are incorporated into these foods and beverages, etc. The casein hydrolysate and resistant dextrin of the present technology can be used as they are for animals including humans, or can be mixed with a conventional carrier or diluent that is nutrient- or medicamentally acceptable for use, thereby enabling the present technology to exert the various effects described above. Furthermore, the casein hydrolysate and resistant dextrin of the present technology can be used for producing these various compositions or preparations, etc.

[0058] Additionally, the present embodiments may be for therapeutic or non-therapeutic uses. "Non-therapeutic purposes" is a concept that does not include medical procedures, i.e., treatment of the human body through therapy. Examples include health promotion and cosmetic procedures. "Amelioration" refers to improving a disease, symptom, or condition; preventing or slowing the worsening of a disease, symptom, or condition; or reversing, preventing, or slowing the progression of a disease or symptom. "Prevention" refers to preventing or delaying the onset of a disease or condition in a subject, or reducing the risk of a disease or condition in a subject.

[0059] The casein hydrolysate and resistant dextrin according to the present technology, and compositions containing them for lowering blood pressure and / or lowering neutral fats, and for lowering blood pressure and / or lowering neutral fats, and for preventing, ameliorating, or treating hypertension and / or dyslipidemia (hyperlipidemia) (hereinafter also referred to as "compositions, etc.") may be used in any of pharmaceuticals, foods and beverages, or feeds (preferably pet food) by taking advantage of their excellent blood pressure lowering effect and / or neutral fat lowering effect.

[0060] The casein hydrolysate and resistant dextrin used in this technology are easily soluble in water and therefore have excellent processing stability. In addition, since the efficacy of this technology is exerted by oral ingestion, it is preferable to use them for oral ingestion.

[0061] The form of the composition of the present technology is not particularly limited, but powder or granules, compressed tablets, or tablets such as capsules filled in capsules are preferred. The composition of the present technology may be in a unit package form. The composition in the unit package form may contain the two components of the present technology as a unit package, and may be packaged in the form of separate formulations or compositions, such as a formulation containing casein hydrolysate and a formulation containing resistant dextrin, or may be packaged in a form in which the two components of the present technology are mixed together in a powdered state or the like. From the viewpoint of convenience, a unit package form per meal is preferred.

[0062] The content or amount of casein hydrolysate used in the composition etc. according to the present technology can be freely set according to age, symptoms etc., as long as it does not impair the efficacy of the present technology. In this technique, the content of casein hydrolysate can be set to 0.001 to 1% by mass with respect to the final composition. Furthermore, in the present technology, the content of the tripeptide MKP can be set to 0.00001 to 0.005% by mass with respect to the final composition. As used herein, final composition refers to the composition as it is administered to or ingested by a subject. In the present technology, the amount of casein hydrolysate used for a subject is preferably 0.0001 to 1 g / kg body weight / day, more preferably 0.0005 to 0.5 g / kg body weight / day, and even more preferably 0.0001 to 0.1 g / kg body weight / day.

[0063] The content or amount of resistant dextrin used in the present technology can be freely set according to age, symptoms, etc., as long as it does not impair the efficacy of the present technology. In the present technology, for example, when the amount of resistant dextrin per meal is about 5 g, the content of resistant dextrin can be set to 1 to 10% by mass with respect to the final composition. In the present technology, the amount of resistant dextrin used for a subject is preferably 0.001 to 10 g / kg body weight / day, more preferably 0.005 to 5 g / kg body weight / day, and even more preferably 0.01 to 1 g / kg body weight / day.

[0064] The individual contents or amounts of casein hydrolysate and resistant dextrin used in the present technology are not particularly limited; however, in terms of the ratio of their contents or amounts used, in order to better exert the efficacy of the present technology, it is preferable that they are contained in a ratio of resistant dextrin:casein hydrolysate=10:0.001 to 1:1, and it is even more preferable that they are contained in a ratio of resistant dextrin:casein hydrolysate=1:0.001 to 10:1. In addition, the individual contents or amounts of tripeptide MKP:resistant dextrin used in the present technology are not particularly limited, but in order to better exert the efficacy of the present technology, the lower limit of the resistant dextrin relative to 1 part by mass of tripeptide MKP is preferably 5,000 parts by mass or more, more preferably 10,000 parts by mass or more, and the upper limit is preferably 100,000 parts by mass or less, more preferably 80,000 parts by mass or less, and within this range, the resistant dextrin is preferably 15,000 to 50,000 parts by mass.

[0065] In the present technology, the casein hydrolysate and the resistant dextrin can be used simultaneously or separately, as long as the efficacy of the present technology is not impaired. In addition, the interval of use of the present technology (specifically, the interval of administration or ingestion) is not particularly limited, and may be once a day or may be divided into several times a day. In addition, it is preferable to use the present technology continuously every day (specifically, administer or ingestion). In addition, the casein hydrolysate and resistant dextrin used in the present technology are empirically highly safe, and can be taken continuously for a long period of time. The present technology is excellent in that the preventive effect of the technology can be continuously exerted by continuous long-term use, and it is desirable to use it continuously every day, for example, for 30 days or more.

[0066] The subject of the present technology is not particularly limited, and may be humans or non-human animals. In addition, since both ingredients of the present technology are highly safe and can be taken for a long period of time, they can be used by people of all ages and genders. Since the present technology has a blood pressure lowering effect and / or a triglyceride lowering effect, the target subjects of the present technology are preferably those expecting to lower blood pressure and / or reduce triglycerides, and those who may be at risk or are at high risk of hypertension and / or dyslipidemia.

[0067] <Medicines, quasi-drugs> Taking advantage of its excellent efficacy, this technology can be used by being incorporated into human or animal pharmaceuticals, quasi-drugs, etc. (hereinafter referred to as "pharmaceuticals, etc.") as an active ingredient for use in lowering blood pressure and / or reducing neutral fats, and in the prevention, improvement, and treatment of hypertension and / or dyslipidemia (hyperlipidemia).

[0068] When compounded with pharmaceuticals, the pharmaceuticals can be formulated into a desired dosage form depending on the administration method, such as oral administration or parenteral administration. The dosage form is not particularly limited, but in the case of oral administration, it can be formulated into solid preparations such as powders, granules, tablets, lozenges, capsules, and liquid preparations such as solutions, syrups, suspensions, and emulsions. In the case of parenteral administration, it can be formulated into suppositories, sprays, inhalants, ointments, patches, injections, and the like. In the present technology, it is preferable to formulate into a dosage form for oral administration. The formulation can be carried out by a known method depending on the dosage form.

[0069] When preparing a formulation, a formulation may be prepared by appropriately blending a pharmaceutical carrier. In addition to the peptide of the present technology, components such as excipients, pH adjusters, colorants, and flavorings that are usually used in formulations can be used. Furthermore, components that have known or future-discovered effects for preventing, improving, and / or treating diseases or symptoms can also be used in combination as appropriate depending on the purpose.

[0070] As the pharmaceutical carrier, various organic or inorganic carriers can be used depending on the dosage form. Examples of carriers in the case of solid preparations include excipients, binders, disintegrants, lubricants, stabilizers, flavoring agents, etc.

[0071] Examples of the excipient 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, hydroxypropylmethyl cellulose, carboxymethyl cellulose, and carboxymethyl cellulose 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.

[0072] Examples of the binder include gelatin, polyvinylpyrrolidone, macrogol, and the like, in addition to the above-mentioned excipients.

[0073] Examples of the disintegrant include the above-mentioned excipients, as well as chemically modified starch or cellulose derivatives such as croscarmellose sodium, sodium carboxymethyl starch, and crosslinked polyvinylpyrrolidone.

[0074] Examples of the lubricants include talc; stearic acid; metal stearates such as calcium stearate and magnesium stearate; colloidal silica; waxes such as pea gum and geranium stearate; boric acid; glycol; carboxylic acids such as fumaric acid and adipic acid; sodium carboxylates 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 silicic anhydride and silicic acid hydrate; starch derivatives, and the like.

[0075] Examples of the stabilizer include paraoxybenzoic acid esters such as methylparaben and propylparaben; alcohols such as chlorobutanol, benzyl alcohol and phenylethyl alcohol; benzalkonium chloride; acetic anhydride; and sorbic acid.

[0076] Examples of the flavoring agent include sweeteners, acidulants, and fragrances. In the case of a liquid preparation for oral administration, examples of the carrier used include a solvent such as water, a flavoring agent, and the like.

[0077] The content of casein hydrolysate used in the pharmaceutical product of the present technology can be freely set according to age, symptoms, etc., as long as it does not impair the effect of the present technology. In particular, the content of casein hydrolysate in the present technology can be set to 0.001 to 1% by mass of the final composition of the pharmaceutical product. In the present technology, the amount of casein hydrolysate used for a subject is preferably 0.0001 to 1 g / kg body weight / day, more preferably 0.0005 to 0.5 g / kg body weight / day, and even more preferably 0.001 to 0.1 g / kg body weight / day.

[0078] Furthermore, the content of resistant dextrin used in the pharmaceutical product, etc. according to the present technology can be freely set according to age, symptoms, etc., as long as it does not impair the effects of the present technology. In the present technology, for example, when the amount of resistant dextrin per meal is about 5 g, the content of resistant dextrin can be set to 1 to 10% by mass of the final composition of the pharmaceutical product, etc. In the present technology, the amount of resistant dextrin used for a subject is preferably 0.001 to 10 g / kg body weight / day, more preferably 0.005 to 5 g / kg body weight / day, and even more preferably 0.01 to 1 g / kg body weight / day.

[0079] Thus, in a composition provided in the form of a pharmaceutical or the like, the individual contents or amounts of resistant dextrin and casein hydrolysate used are not particularly limited; however, in terms of the ratio of the contents or amounts used, from the viewpoint of better exerting the efficacy of the present technology, it is preferable that the contents be in a mass ratio of resistant dextrin:casein hydrolysate=10:0.001 to 1:1, and it is more preferable that the contents be in a mass ratio of resistant dextrin:casein hydrolysate=1:0.001 to 10:1. Furthermore, in the present technology, the individual contents or amounts of tripeptide MKP:resistant dextrin used are not particularly limited, but from the viewpoint of better exerting the efficacy of the present technology, the lower limit of the resistant dextrin relative to 1 part by mass of tripeptide MKP is preferably 5,000 parts by mass or more, more preferably 10,000 parts by mass or more, and the upper limit is preferably 100,000 parts by mass or less, more preferably 80,000 parts by mass or less, and within this range, the resistant dextrin is preferably 15,000 to 50,000 parts by mass.

[0080] <Food and drink> Taking advantage of its excellent efficacy, this technology can be used by being blended into human or animal foods and beverages, health foods, functional foods, foods for the sick, enteral nutritional foods, special dietary foods, health functional foods, foods for specified health uses, functional foods and foods with nutritional claims that are labeled as being useful for lowering blood pressure and / or lowering neutral fats, and for preventing, improving, or treating hypertension and / or dyslipidemia (hyperlipidemia), etc. (hereinafter referred to as "foods and beverages, etc.").

[0081] The present technology can be used to prepare food and beverage products by adding it to known foods and beverage products, or to produce new food and beverage products by mixing it into the ingredients of foods and beverage products.

[0082] The food and beverages may be in any form, such as liquid, paste, solid, powder, etc., and may include, for example, wheat flour products, instant foods, processed agricultural products, processed marine products, processed livestock products, milk and dairy products, oils and fats, basic seasonings, compound seasonings and foods, frozen foods, confectioneries, beverages, and other commercially available products.

[0083] Examples of the wheat flour products include bread, macaroni, spaghetti, noodles, cake mix, fried chicken flour, bread crumbs, etc. Examples of the instant foods include instant noodles, cup noodles, retort / prepared foods, preparatory canned foods, microwave foods, instant soups / stews, instant miso soup / cleansing liquids, canned soups, freeze-dried foods, and other instant foods. Examples of the processed agricultural products include canned agricultural products, canned fruits, jams and marmalades, pickles, boiled beans, dried agricultural products, and cereals (processed grain products). Examples of the processed marine products include canned marine products, fish ham and sausage, marine paste products, marine delicacies, and tsukudani. Examples of the processed livestock products include canned livestock products, pastes, livestock ham, sausages, and the like. Examples of the milk and dairy products include processed milk, milk drinks, yogurts, lactic acid bacteria drinks, cheese, ice creams, infant formula, cream, and other dairy products. Examples of the fats and oils include butter, margarines, vegetable oils, and the like. Examples of the basic seasonings include soy sauce, miso, sauces, tomato processed seasonings, mirin, vinegars, etc., and examples of the complex seasonings and foods include cooking mixes, curry bases, sauces, dressings, noodle soups, spices, and other complex seasonings. Examples of the frozen foods include raw frozen foods, semi-cooked frozen foods, cooked frozen foods, and the like. Examples of the sweets include caramel, candy, chewing gum, chocolate, cookies, biscuits, cakes, pies, snacks, crackers, Japanese sweets, rice sweets, bean sweets, dessert sweets, and other sweets. Examples of the beverages include carbonated beverages, natural fruit juices, fruit juice beverages, soft drinks containing fruit juice, fruit pulp beverages, fruit beverages containing fruit particles, vegetable beverages, soy milk, soy milk beverages, coffee beverages, tea beverages, powdered beverages, concentrated beverages, sports beverages, nutritional beverages, alcoholic beverages, and other beverages of your choice. Other commercially available foods include, for example, baby food, furikake, and ochaku-nori seaweed.

[0084] [Method for producing food and beverages according to the present technology] The food and drink of the present technology can be produced by adding casein hydrolysate and resistant dextrin to the raw materials of the food and drink composition, and can be produced in the same manner as a normal food and drink composition except for adding the casein hydrolysate and resistant dextrin. The casein hydrolysate and resistant dextrin of the present technology may be added at any stage of the production process of the food and drink composition. The food and beverage products of the present technology can be supplemented with beneficial bacteria, and among the food and beverage products that contain beneficial bacteria, fermented food and beverage products are preferred, as they can add a probiotic effect through the fermentation of beneficial bacteria. In the method for producing the fermented food or drink, the casein hydrolysate and the resistant dextrin may be added at any stage of the production process. For example, the fermented food or drink may be produced by containing these as raw materials and undergoing a fermentation process. Examples of such food or drink include lactic acid bacteria beverages and fermented milk.

[0085] [Fermented food and beverages and their manufacturing method according to the present technology] The method for producing fermented food and drink according to the present technology will be described below, but is not limited thereto. In the method for producing a fermented food or drink according to the present invention, a casein hydrolysate and / or a resistant dextrin can be used as raw materials for the fermented food or drink. The casein hydrolysate and / or the resistant dextrin can be used either before and / or after the fermentation process of the fermented food or drink.

[0086] In addition, the raw materials used in the manufacturing method of the present technology are raw materials that may be used in any step of the manufacturing method of fermented milk, unless otherwise specified, and may be used as raw materials for pre-fermentation and / or post-fermentation. In order to more effectively exert the effects of the present technology, it is preferable to use, as the raw material, one or more kinds selected from the group consisting of low-calorie sweeteners, rare monosaccharides, and milk oligosaccharides. As the raw materials, in order to improve flavor, it is preferable to use a low-calorie sweetener and / or a rare sugar, and it is more preferable to use a low-calorie sweetener and a rare sugar in combination. It is preferable to use milk oligosaccharides (preferably lactulose) as the raw material, because they can impart a milk flavor, reach the large intestine without being broken down and absorbed, become a nutrient for bifidobacteria, and promote the absorption of calcium and magnesium. The content of the low-calorie sweetener in the final product is preferably 0.001 to 0.1% by mass. The content of the rare sugar in the final product is preferably 0.005 to 0.25% by mass. The content of lactulose in the final product is preferably 0.5 to 6% by mass.

[0087] Examples of the low-calorie sweetener include aspartame, acesulfame K, sucralose (also known as 4,1',6'-trichlorogalactosucrose), stevia sweetener, saccharin, sodium saccharinate, licorice extract, etc. Commercially available products may be used. One or more types selected from the group consisting of these may be selected, and among these, sucralose is preferred. Examples of the rare monosaccharide include D-psicose and D-allose, and commercially available products may be used, such as rare sugar-containing syrup (Rare Sugar Sweet (manufactured by Matsutani Chemical Industry Co., Ltd.)). Among these, D-psicose and / or D-allose are preferred, and a combination of D-psicose and D-allose is more preferred. As the lactulose-containing product, a commercially available product may be used, and examples of the commercially available product include milk oligosaccharides MLC-90, MLP-95, and MLS-95 (manufactured by Morinaga Milk Industry Co., Ltd.) The milk oligosaccharide contains preferably 30% by mass or more of lactulose, more preferably 40% by mass or more, and even more preferably 50% by mass or more.

[0088] An example of using casein hydrolysate and resistant dextrin as raw materials before fermentation will be described below, but the method for producing fermented foods and beverages of the present technology is not limited to this. In the manufacturing method of the present technology, a milk preparation containing casein hydrolysate and resistant dextrin as fermented milk ingredients is sterilized, and fermentation bacteria is added to the sterilized milk preparation to ferment it until the pH reaches 5.0 or less. It is preferable to add a lactic acid bacteria starter and / or a Bifidobacterium genus bacterium as the fermentation bacteria for fermentation.

[0089] As the raw material for the fermented milk used in this technology, general raw materials for fermented milk can be used, except that casein hydrolysate and resistant dextrin are blended. Common fermented milk ingredients are not particularly limited as long as they are milk-derived ingredients that can be fermented with fermenting bacteria to produce fermented foods and beverages, and examples of such ingredients include milk or its fractions or processed products (e.g., cow's milk, skim milk, fresh cream, butter, whole milk powder, skim milk powder, or mixtures, dissolution or suspension of these in water, etc.) The origin of the milk from an animal is not particularly limited, but milk derived from cows is preferred. The fermented milk raw material may contain optional ingredients such as sweeteners such as sucrose, pectin, fruit, fruit juice, agar, gelatin, oils and fats, flavorings, coloring agents, stabilizers, reducing agents, etc., as necessary. The fermented milk raw material may be subjected to sterilization, homogenization, cooling, etc., according to conventional methods before fermentation.

[0090] Fermentation may be carried out by adding fermentation bacteria including a lactic acid bacteria starter and / or a Bifidobacterium genus bacterium to the fermented milk raw material (preferably a milk preparation). Any of these fermentation bacteria may be inoculated multiple times.

[0091] Furthermore, the "lactic acid bacteria starter" to be inoculated into the fermented milk raw material may be a single strain or a combination of multiple strains. The "lactic acid bacteria starter" in the present technology is not particularly limited as long as it is used in the production of food and drink. For example, when the fermented food and drink is yogurt, the "lactic acid bacteria starter" may be Lactobacillus bulgaricus, Lactobacillus delbrueckii subsp. bulgaricus, Streptococcus thermophilus, etc., and these lactic acid bacteria may be a single strain or a combination of multiple strains.

[0092] The amount of the fermentation bacteria of the present technology to be inoculated into the fermented milk raw material is not particularly limited. The lactic acid bacteria and Bifidobacterium bacteria of the present technology are preferably 10 4 ~10 9 CFU / mL milk ingredient, preferably 10 6 ~10 8 CFU / mL milk source. The Bifidobacterium bacterium is preferably 10 5 ~10 9 CFU / mL milk ingredient, preferably 10 7 ~10 8 CFU / mL milk source.

[0093] It is preferable that the Bifidobacterium bacteria and / or other lactic acid bacteria to be inoculated into the fermented milk raw material are seed-cultured or pre-cultured in advance in another medium. The medium used prior to the main culture is not particularly limited as long as it is a medium suitable for culturing Bifidobacterium genus bacteria and / or other lactic acid bacteria, and examples thereof include a medium containing reconstituted skim milk powder. The concentration of the reduced skim milk powder is preferably 3% (W / W) or more, particularly preferably 8% (W / W) or more. A growth promoter such as yeast extract, a reducing agent such as L-cysteine, etc. may be added to the medium used for seed culture or preculture. In particular, when using Bifidobacterium bacteria, the proliferation rate in a medium containing reduced skim milk powder is low, so it is preferable to use a medium containing a growth promoter, for example, 0.1 to 1% (w / w) yeast extract. The sterilization conditions for the medium are the same as those described above.

[0094] In the method for producing a fermented food or drink according to the present technology, the fermentation conditions such as culture temperature and culture time can be the same as those for producing a fermented food or drink from a normal milk raw material. For example, the culture temperature is preferably 30° C. to 42° C., more preferably 36° C. to 40° C. The culture time can be appropriately set depending on the type of fermented food or drink to be produced, but is usually preferably 4 to 18 hours.

[0095] The fermented food and drink obtained by the method for producing the fermented food and drink of the present technology can be appropriately processed in the same manner as fermented food and drink made from normal dairy raw materials. For example, the fermented food and drink after fermentation may be used as it is, or may be homogenized and processed into a liquid form. In addition, sweeteners such as sucrose, pectin, fruit, fruit juice, agar, gelatin, oils and fats, flavors, colorants, stabilizers, reducing agents, etc. may be added. The fermented food and drink may also be filled into a container as appropriate.

[0096] The fermented food and beverage obtained as described above contains casein hydrolysate and resistant dextrin, which allows the efficacy of the present technology to be effectively exerted.

[0097] [Food and beverages with functional claims] In addition, the foods and beverages defined by this technology can also be provided and sold as foods and beverages with specific uses (especially health uses) or functions indicated. The act of "representation" includes all acts aimed at informing consumers of the above-mentioned uses, and any expression that can recall or infer the above-mentioned uses falls under the act of "representation" of this technology, regardless of the purpose of the representation, the content of the representation, the object or medium on which it is displayed, etc.

[0098] Furthermore, it is preferable that the "labeling" be done in an expression that allows consumers to directly recognize the above-mentioned uses.Specific examples include the act of transferring, delivering, displaying for the purpose of transferring or delivering, or importing food and beverage products or product packaging on which the above-mentioned uses are written, displaying or distributing advertisements, price lists, or transaction documents related to the products and writing the above-mentioned uses in information containing the above-mentioned uses and providing them by electromagnetic means (such as the Internet), etc.

[0099] On the other hand, the content of the labeling is preferably a labeling approved by the government etc. (for example, a labeling approved based on various systems established by the government and made in a manner based on such approval, etc.) In addition, it is preferable that such a labeling content is affixed to the packaging, containers, catalogs, pamphlets, POP and other sales site promotional materials, other documents, etc.

[0100] In addition, "labeling" also includes labeling as health food, functional food, food for the sick, enteral nutritional food, special purpose food, health functional food, food for specified health uses, functional food, nutritional functional food, medical drug, etc. Among these, in particular, labeling approved by the Consumer Affairs Agency, such as labeling approved under the Food for Specified Health Uses system, the Food for Functional Uses system, and similar systems, can be mentioned. More specifically, labeling as a food for specified health uses, labeling as a food with conditional health use, labeling as a food with functional claims, labeling that affects the structure or function of the body, labeling for reducing the risk of disease, etc. Among these, typical examples include labeling as a food for specified health uses (especially labeling of health uses) as specified in the Enforcement Regulations of the Health Promotion Act (Ministry of Health, Labor and Welfare Ordinance No. 86 of April 30, 2003), labeling as a food with functional claims as specified in the Food Labeling Act (Act No. 70 of 2013), and similar labels.

[0101] The content of casein hydrolysate used in the food, beverage, etc. according to the present technology can be freely set according to age, symptoms, etc., as long as it does not impair the effect of the present technology. In particular, the content of casein hydrolysate in the present technology can be set to 0.001 to 1% by mass with respect to the final composition of the food, beverage, etc. In the present technology, the amount of casein hydrolysate used for a subject is preferably 0.0001 to 1 g / kg body weight / day, more preferably 0.0005 to 0.5 g / kg body weight / day, and even more preferably 0.001 to 0.1 g / kg body weight / day.

[0102] Furthermore, the content of resistant dextrin used in the food, beverage, etc. according to the present technology can be freely set according to age, symptoms, etc., as long as it does not impair the effects of the present technology. In the present technology, for example, when the amount of resistant dextrin per meal is about 5 g, the content of resistant dextrin can be set to 1 to 10% by mass with respect to the final composition of the food, beverage, etc. In the present technology, the amount of resistant dextrin used for a subject is preferably 0.001 to 10 g / kg body weight / day, more preferably 0.005 to 5 g / kg body weight / day, and even more preferably 0.01 to 1 g / kg body weight / day.

[0103] As described above, in a composition provided in the form of a food or beverage, etc., the individual contents of resistant dextrin and casein hydrolysate are not particularly limited; however, in terms of the content or ratio of the amounts of these contained, from the viewpoint of exerting better efficacy of the present technology, it is preferable that the mass ratio of resistant dextrin:casein hydrolysate be 10:0.001 to 1:1, and it is more preferable that the mass ratio of resistant dextrin:casein hydrolysate be 1:0.001 to 10:1. Furthermore, in the present technology, the individual contents or amounts of tripeptide MKP:resistant dextrin used are not particularly limited, but from the viewpoint of better exerting the efficacy of the present technology, the lower limit of the resistant dextrin relative to 1 part by mass of tripeptide MKP is preferably 5,000 parts by mass or more, more preferably 10,000 parts by mass or more, and the upper limit is preferably 100,000 parts by mass or less, more preferably 80,000 parts by mass or less, and within this range, the resistant dextrin is preferably 15,000 to 50,000 parts by mass.

[0104] <Feed> Taking advantage of its excellent efficacy, this technology can be used as an active ingredient in animal feed for lowering blood pressure and / or reducing neutral fat, and for preventing, improving, and treating hypertension and / or dyslipidemia (hyperlipidemia). This technology can be added to existing feed to prepare it, or it can be mixed into the raw materials of feed to produce new feed.

[0105] Examples of the raw materials for the feed include cereals such as corn, wheat, barley, rye, etc.; bran, wheat bran, rice bran, defatted rice bran, etc.; production residues such as corn gluten meal and corn jam meal; animal feeds such as skim milk powder, whey, fish meal, bone meal, etc.; yeasts such as brewer's yeast; mineral feeds such as calcium phosphate and calcium carbonate; oils and fats; amino acids; sugars, etc. Examples of the form of the feed include pet feeds (pet food, etc.), livestock feeds, fish feeds, etc.

[0106] The content of the casein hydrolysate used in the feed according to the present technology can be freely set according to the body weight, symptoms, etc., as long as it does not impair the effects of the present technology. In particular, the content of the casein hydrolysate in the present technology can be set to 0.001 to 1% by mass with respect to the final composition of the feed. In the present technology, the amount of casein hydrolysate used is preferably 0.0001 to 1 g / kg body weight / day, more preferably 0.0005 to 0.5 g / kg body weight / day, and even more preferably 0.0001 to 0.1 g / kg body weight / day.

[0107] Furthermore, the content of resistant dextrin used in the feed according to the present technology can be freely set according to the body weight, symptoms, etc., as long as it does not impair the effects of the present technology. In the present technology, for example, when the amount of resistant dextrin per meal is about 5 g, the content of resistant dextrin can be set to 1 to 10 mass% of the final composition of the feed. In the present technology, the amount of resistant dextrin used is preferably 0.001 to 10 g / kg body weight / day, more preferably 0.005 to 5 g / kg body weight / day, and even more preferably 0.01 to 1 g / kg body weight / day.

[0108] Thus, in a composition provided in the form of a feed, the individual contents or amounts of resistant dextrin and casein hydrolysate used are not particularly limited; however, in terms of the ratio of the contents or amounts used, from the viewpoint of better exerting the efficacy of the present technology, it is preferable that the resistant dextrin:casein hydrolysate be contained in a mass ratio of 10:0.001 to 1:1, and it is more preferable that the resistant dextrin:casein hydrolysate be contained in a mass ratio of 1:0.001 to 10:1. Furthermore, in the present technology, the individual contents or amounts of tripeptide MKP:resistant dextrin used are not particularly limited, but from the viewpoint of better exerting the efficacy of the present technology, the lower limit of the resistant dextrin relative to 1 part by mass of tripeptide MKP is preferably 5,000 parts by mass or more, more preferably 10,000 parts by mass or more, and the upper limit is preferably 100,000 parts by mass or less, more preferably 80,000 parts by mass or less, and within this range, the resistant dextrin is preferably 15,000 to 50,000 parts by mass.

[0109] It should be noted that the present technology can also employ the following configuration. [1] A composition for lowering blood pressure and / or reducing neutral fats, and for preventing, improving and treating hypertension and / or dyslipidemia (hyperlipidemia), comprising casein hydrolysate and resistant dextrin. [2] A method for lowering blood pressure and / or reducing neutral fat, and a method for preventing, ameliorating, or treating hypertension and / or dyslipidemia (hyperlipidemia), which comprises administering or ingesting casein hydrolysate and resistant dextrin. [3] A casein hydrolysate and a resistant dextrin for use in lowering blood pressure and / or reducing neutral fats, and for preventing, improving or treating hypertension and / or dyslipidemia (hyperlipidemia), or use thereof. [4] Use of a casein hydrolysate and a resistant dextrin for producing a composition for lowering blood pressure and / or reducing neutral fats, and a composition for preventing, improving and treating hypertension and / or dyslipidemia (hyperlipidemia).

[0110] [5] Preferably, any one of the casein hydrolysates [1] to [4] above contains a peptide consisting of Met-Lys-Pro. [6] Preferably, in any one of the above items [1] to [5], the resistant dextrin and the casein hydrolysate are contained in a mass ratio of 10:0.001 to 1:1. [7] Preferably, any one of the casein hydrolysates [1] to [6] contains the peptide consisting of Met-Lys-Pro. More preferably, the amount of indigestible dextrin is 5,000 to 100,000 parts by mass per part by mass of the peptide. [8] Preferably, in any one of the above [1] to [7], the composition is for use in medicines or foods and beverages. [9] Preferably, in any one of the above [1] to [8], the composition is for use in a fermented food or drink.

[10] Preferably, any one of the above items [1] to [9] is in a unit package form.

[11] Preferably, in any one of the above items [1] to

[10] , the composition is in the form of a powder or granules, a compressed tablet, or a tablet filled in a capsule, or these are used.

[12] Preferably, in any one of the above [1] to

[11] , the casein hydrolysate is contained in an amount of 0.001 to 1 mass % relative to the mass of the final composition.

[13] Preferably, in any one of the above [1] to

[12] , the indigestible dextrin is contained in an amount of 1 to 10% by mass relative to the mass of the final composition.

[14] A method for lowering blood pressure and / or a method for lowering neutral fat, and a method for preventing, improving or treating hypertension and / or dyslipidemia (hyperlipidemia), using any one of the compositions according to [1] to

[13] . EXAMPLES

[0111] The present technology will be described in more detail below based on examples. Note that the examples described below are representative examples of the present technology, and the scope of the present technology is not to be interpreted narrowly by these examples.

[0112] [Production Example 1] 900 mg of water was added to 100 mg of commercially available casein (manufactured by New Zealand Dairy Board) and thoroughly dispersed. Sodium hydroxide was added to adjust the pH of the solution to 7.0 to completely dissolve the casein, preparing an aqueous casein solution with a concentration of approximately 10%. The casein aqueous solution was sterilized by heating at 85°C for 10 minutes, the temperature was adjusted to 50°C, sodium hydroxide was added to adjust the pH to 9.0, and then 2 mg of pancreatin (Amano Enzyme Co., Ltd.) and 4 mg of protease A (Amano Enzyme Co., Ltd.) were added to initiate the hydrolysis reaction. After 8 hours, the enzyme reaction was stopped by inactivating the enzyme by heating at 80°C for 6 minutes, and cooled to 10°C. This hydrolyzate was ultrafiltered using an ultrafiltration membrane with a molecular weight cutoff of 1000 (manufactured by Nippon Pall Corporation), concentrated and then freeze-dried to obtain 85 mg of casein hydrolyzate.

[0113] As a result of carrying out the above process for multiple lots, the casein hydrolysate had a decomposition rate of 20-30%, an average molecular weight of 800 Da or less, an amino acid release rate of 10% or less, and a tripeptide MKP content of 0.01-0.1% by mass. These were calculated using the above-mentioned <Amino acid decomposition rate>, <Calculation method for average molecular weight>, <Calculation method for amino acid release rate>, and <Measurement of tripeptide MKP content>. Casein hydrolysate can be prepared to have an average molecular weight of 360-390 Da.

[0114] [Example 1] In this example, changes in serum triglyceride (TG) levels were evaluated when rats were loaded with lipids.

[0115] (1) Sample preparation Test sample 1 + test sample 2 were prepared by using water for injection (manufactured by Otsuka Pharmaceutical Factory, Inc.) containing 1% by mass of casein hydrolysate (test sample 1) alone and 10% by mass of indigestible dextrin (Fibersol 2: manufactured by Matsutani Chemical Industry Co., Ltd.) (test sample 2) alone. Water for injection was used as a control sample. (2) Test method Male Slc:SD (SPF) rats were purchased from Japan SLC Co., Ltd. at 6 weeks of age. After one week of preliminary breeding in Labo MR Stock (Nihon Nosan Kogyo Co., Ltd.), they were divided into two groups of eight rats each: Group A (control) and Group B (administered test sample 1 + test sample 2). They were fasted overnight (approximately 16 hours) from the evening of the day before the lipid loading test, and blood was collected from the tail vein (blood collection at 0 hours elapsed). The control sample or test sample was forcefully administered orally at a rate of 10 mL / kg. Immediately after administration, corn oil was forcibly administered orally at a rate of 3 g / kg. Blood samples were taken 2, 4, 5, and 6 hours after administration. After blood collection at each time point, the blood was centrifuged and serum was separated. The serum was used to measure blood triglycerides using a 7070 automatic analyzer (Hitachi, Ltd.).

[0116] (3) Test results The time course of serum TG concentration is shown in Table 1. The values ​​in the table are shown as the mean and standard error. Significant differences were examined by testing for homogeneity of variance using the Bartlett method, and if homogeneity of variance was found, one-way analysis of variance was performed. If significant, the mean values ​​were compared using the Dunnett method.

[0117] [Table 1]

[0118] As shown in Table 1, suppression of blood TG increase was observed in group B compared to group A. From the above results, it was found that the combined use of casein hydrolysate and resistant dextrin has the effect of suppressing the increase in blood lipids.

[0119] [Example 2] In this example, the blood pressure lowering effect in hypertensive rats was evaluated.

[0120] (1) Sample preparation Test sample 1 + test sample 2 were prepared by using water for injection (manufactured by Otsuka Pharmaceutical Factory, Inc.) containing 1% by mass of casein hydrolysate (test sample 1) alone and 10% by mass of indigestible dextrin (Fibersol 2: manufactured by Matsutani Chemical Industry Co., Ltd.) (test sample 2) alone. Water for injection was used as a control sample. (2) Test method Male SHR / Hos rats (SPF) were purchased from Japan SLC Co., Ltd. at 10 weeks of age. After one week of preliminary breeding, the rats were divided into two groups of six rats each: group A (control) and group B (administered with test sample 1 + test sample 2). After grouping, blood pressure was measured for the animals before administration and at 2, 4, 6, 8, and 24 hours after administration. For blood pressure, systolic blood pressure was measured by the tail cuff method using a non-invasive automatic blood pressure measuring device (BP-98A, Softron Co., Ltd.) under no anesthesia. Measurements are performed three times, and the average is used as the measured value for each individual. Before measurement, place the animal in a warming box (set temperature: 38°C) for about 5 minutes to raise its body temperature.

[0121] (3) Test results Changes in systolic blood pressure over time are shown in Table 2. Note that the table significance test is a two-group comparison test. The F test is used to test for homogeneity of variance between the two groups, and in the case of equal variance, a Student's t-test is used. For all tests, a significance level of less than 5% is considered significant, and values ​​are displayed separately for less than 5% (p < 0.05) and less than 1% (p < 0.01).

[0122] [Table 2]

[0123] As shown in Table 2, a decrease in blood pressure was observed in group B compared with group A. From the above results, it was found that the combined use of casein hydrolysate and resistant dextrin has a blood pressure lowering effect.

[0124] [Production Example 1] The casein hydrolysate and indigestible dextrin of Production Example 1, as well as sucralose (manufactured by San-Ei Gen FF Co., Ltd.) and a rare monosaccharide (product name: Rare Sugar Sweet (manufactured by Matsutani Chemical Industry Co., Ltd.)) were blended with milk or skim milk to produce a beverage containing (A) 3.5% by mass or more of milk protein and (B) milk fat. The infant formula is prepared to contain (A) 3.5% by mass or less of niacin, (B) 5.0% by mass or more of carbohydrates, and (C) 0.15% by mass or more of calcium. The milk preparation liquid, lactic acid bacteria, and bifidobacteria are mixed uniformly and then fermented. This produces a composition for lowering blood pressure and / or reducing neutral fat, which contains casein hydrolysate and resistant dextrin (fermented milk). The fermented milk contains (E) 0.3-0.8% by mass of the casein hydrolysate of Example 1, (F) 4-8% by mass of resistant dextrin, (G) 0.05-0.02% by mass of sucralose, (H) 0.05-0.1% by mass of D-psicose and D-allose, and (I) 1-4% by mass of lactulose. The fermented milk for lowering blood pressure and / or lowering neutral fat of the present technology is consumed every day so that the daily intake of casein hydrolysate and resistant dextrin is 0.0001-1 g / kg body weight / day for casein hydrolysate and 0.001-10 g / kg body weight / day for resistant dextrin, respectively. This is expected to have the effect of lowering blood pressure and / or lowering neutral fat.

[0125] [Formulation Example 1: Powder for lowering blood pressure and / or reducing neutral fat] The components (powders) shown in Table 3 are mixed to obtain a powder for lowering blood pressure and / or reducing neutral fat. The powder can be used as a supplement, and can be mixed with water to make a beverage. The powder can be filled into a capsule container or encapsulated to make a capsule for lowering blood pressure and / or reducing neutral fat. The powder can be compressed to make a tablet for lowering blood pressure and / or reducing neutral fat. The powder is expected to have the effect of lowering blood pressure and / or reducing neutral fat. The casein hydrolysate and indigestible dextrin of Production Example 1 can be used as raw materials for the powder.

[0126] [Table 3]

Claims

1. A composition for lowering blood pressure and suppressing an increase in neutral fat, comprising a casein hydrolysate and a resistant dextrin, the casein hydrolysate comprises a peptide consisting of Met-Lys-Pro, The composition is used so that the amount of the resistant dextrin administered to a subject of the composition is 0.01 to 1 g / kg body weight / day, The content of the peptide in the composition is 1 part by mass per 5,000 to 100,000 parts by mass of the resistant dextrin. The composition.

2. The composition according to claim 1 , wherein the suppression of an increase in neutral fat is within 6 hours after a meal that includes ingestion of the composition.

3. The composition according to claim 1, which is used for lowering blood pressure and suppressing an increase in neutral fat levels within 6 hours after a meal that includes ingestion of the composition.

4. The composition according to any one of claims 1 to 3, wherein the composition is in the form of a powder, granules, tablet, or capsule.

5. The composition according to any one of claims 1 to 3, wherein the composition is a fermented food or drink.

6. The composition according to any one of claims 1 to 3, which is a pharmaceutical composition or a food or beverage composition.

7. The composition according to any one of claims 1 to 6, which is a composition for lowering blood pressure, suppressing an increase in neutral fat, and suppressing an increase in postprandial blood glucose.

8. A functional food for lowering blood pressure and suppressing an increase in neutral fat, comprising the composition according to any one of claims 1 to 7 as an active ingredient.

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