WO2019160023A1 - Stroke-preventing composition - Google Patents

Abstract

Provided is a stroke-preventing composition that has few side effects and is highly safe. The stroke-preventing composition contains casein hydrolysate and resistant dextrin. Ideally, the casein hydrolysate contains a peptide comprising Met-Lys-Pro. Ideally, the casein hydrolysate contains a peptide comprising Met-Lys-Pro, and the amount of resistant dextrin is 5,000–100,000 parts by mass, inclusive, per 1 part by mass of the peptide.

Description

Stroke prevention composition

This technology relates to a composition for preventing stroke.

The number of deaths from stroke in Japan is about 130,000 per year, accounting for the fourth largest cause of death. In Japan, the number of stroke patients is expected to reach the maximum around 2020, reaching 2875,000, but the number of patients may continue to increase as the population structure ages. Expected. There is a high possibility that after-effects will remain once stroke has occurred, and since the prognosis is shortened, establishment of a method for preventing the onset is required. As a preventive measure against stroke, it is said that the risk of developing stroke is improved by improving lifestyle. (Non-Patent Document 1)

In recent years, it has been reported that the sleep state is involved in stroke as research on the sleep state in the lifestyle is progressing. For example, Non-Patent Document 1 discloses that obstructive sleep apnea syndrome significantly increases the risk of stroke and all-cause death, and that this increase is independent of other risk factors including hypertension. ing. Non-Patent Document 2 discloses that a long sleep time increases death due to stroke or death due to cerebral infarction.
While such research for preventing strokes is progressing, it is difficult to improve lifestyle habits in modern adults, and there is a demand for a composition for preventing strokes that has low side effects, high safety and can be taken for a long time.

Therefore, the main object of the present technology is to provide a composition for preventing strokes with less side effects and high safety.

In order to solve the above-mentioned problems, the present inventors diligently searched for an effective ingredient that exhibits a stroke prevention effect using a stroke model. The present inventors considered that it is appropriate to determine a preventive component using a stroke model because various factors are involved in the occurrence of a stroke event and it is difficult to determine only by one factor. The inventors of the present invention have conducted intensive studies. However, the ingestion of casein hydrolyzate or the indigestible dextrin alone did not provide the expected preventive effect against stroke. In addition, since the indigestible dextrin is known to inhibit the absorption of components in the intestine by forming a viscous gel containing water, the present inventors have added the indigestible dextrin and other components. I thought that it would be difficult to obtain the expected stroke prevention effect even if it was taken in combination for a long time.
However, as a result of further intensive studies, the present inventors are able to obtain a preventive effect that can be expected against stroke by ingesting a combination of casein hydrolyzate and indigestible dextrin in a stroke model. As a result, the present invention has been completed.

In Reference Document 1 (Japanese Patent Laid-Open No. 2017-31105), it has been studied that the combined use of casein hydrolyzate and indigestible dextrin has an effect of suppressing an increase in blood glucose level after a meal. However, from the transient effect of suppressing the increase in blood glucose level after meals, there is no long-term and continuous effect of preventing the onset of stroke, which is a disease caused by clogging or rupture of blood vessels in the brain. can not understand. Moreover, since there is a report (for example, nonpatent literature 2 and 3) that the sleep condition is concerned with the occurrence of the event of a stroke, it cannot be said that a stroke can be prevented immediately only by the situation after a meal.

That is, the present technology is as follows.
[1]
A composition for preventing stroke, comprising casein hydrolyzate and indigestible dextrin.
[2]
The composition according to [1] above, wherein the casein hydrolyzate contains a peptide consisting of Met-Lys-Pro.
[3]
The composition according to [1] or [2] above, wherein the indigestible dextrin and casein hydrolyzate are contained in a mass ratio of 10: 0.001 to 1: 1.
[4]
Any of the above [1] to [3], wherein the casein hydrolyzate contains a peptide consisting of Met-Lys-Pro and is in an amount of 5000 to 100,000 parts by weight of indigestible dextrin with respect to 1 part by weight of the peptide. A composition according to one.
[5]
The composition according to any one of [1] to [4], wherein the composition is used for preventing an initial symptom of stroke.
[6]
The composition according to any one of [1] to [5] above, wherein the composition is a pharmaceutical composition or a food / beverage product composition.
[7]
The composition according to any one of [1] to [6], wherein the composition is a fermented food or drink. [8]
The composition according to any one of [1] to [7], comprising a unit package form.

According to the present technology, it is possible to provide a composition for preventing strokes with less side effects and high safety. In addition, the effect described here is not necessarily limited, and may be any effect described in the present technology.

Hereinafter, preferred embodiments for carrying out the present technology will be described. In addition, embodiment described below shows an example of typical embodiment of this indication, and, thereby, the range of this technique is not interpreted narrowly. In the present specification, regarding the numerical value range expressed as “lower limit to upper limit”, the upper limit may be “less than” or “less than”, and the lower limit may be “greater than”. It may be “super”. In the present specification, the percentage is expressed by mass unless otherwise specified.

This technology can prevent stroke by using a casein hydrolyzate and an indigestible dextrin in combination. The present technology is a composition for preventing stroke, which contains a casein hydrolyzate and an indigestible dextrin as active ingredients, and this composition is preferably a pharmaceutical composition or a food and drink composition (more preferably fermented milk). Can be used.

1. Casein hydrolyzate The casein hydrolyzate used in the present technology is obtained by hydrolyzing casein protein derived from milk. The casein hydrolyzate contains various degradation components derived from casein protein.
The casein hydrolyzate contains at least a peptide (SEQ ID NO: 1) consisting of Met-Lys-Pro (hereinafter, also referred to as “tripeptide MKP”) from the viewpoint of better exerting the effect of the present technology. Is preferred.
The tripeptide MKP of the present technology is known to have effects such as angiotensin converting enzyme inhibitory action, dipeptidyl peptidase-IV inhibitory action (eg, Reference 2 (WO2003 / 044044), Reference 3 ( WO2013 / 125622), Reference 4 (Japanese Patent Laid-Open No. 2016-0669343) and the like.

The casein hydrolyzate preferably contains the tripeptide MKP, and is a combination of one or more conditions selected from the following (a), (b) and (c).
(A) the casein hydrolyzate has an average molecular weight of 1200 daltons or less;
(B) the degradation rate of the casein hydrolyzate is 20-30%,
(C) The mass ratio of the free amino acid in the total mass of all amino acids contained in the casein hydrolyzate is 10% by mass or less.

The content of the tripeptide MKP in the casein hydrolyzate is not particularly limited, but the lower limit is preferably 0.001% by mass or more, more preferably, from the viewpoint of better exerting the effect of the present technology. Is 0.005% by mass or more, still more preferably 0.01% by mass or more, and the upper limit is preferably 1% by mass or less from the viewpoint of the production efficiency of the decomposition product of the present technology, Preferably it is 0.5 mass% or less, More preferably, it is 0.2 mass% or less, More preferably, it is 0.1 mass% or less. The content of the tripeptide MKP is more preferably 0.001 to 1% by mass, further preferably 0.005 to 0.5% by mass, and still more preferably 0.01 to 0.1% by mass.
In addition, the range (a), (b) and (c) in the casein hydrolyzate is preferably in the range prepared in “(2) Method for producing casein hydrolyzate” described later.

Below, the manufacturing method of the casein hydrolyzate used for this technique is explained in full detail.
(1) Raw material Casein, which is a raw material, has a protein derived from milk as a main component, and the casein is not particularly limited. For example, commercially available various caseins, caseinates, and the like can be used. More specifically, lactate casein, sulfate casein, casein hydrochloride, sodium caseinate, potassium caseinate, calcium caseinate, magnesium caseinate, or any mixture thereof can be used. Moreover, casein etc. refine | purified by the conventional method from cow's milk, skim milk, whole fat milk powder, and skim milk powder can also be utilized.

Casein hydrolyzate, which is the active ingredient of this technology, is manufactured by hydrolyzing casein, which is a raw material derived from milk that is relatively inexpensive as a biomaterial. Therefore, it should be manufactured stably and simply in large quantities. Can do.

(2) Method for Producing Casein Hydrolyzate The method for producing casein hydrolyzate is not particularly limited, and examples thereof include a method using an acid or an alkali, a method using an enzyme such as a proteolytic enzyme, and the like. Of these, the use of an enzyme is preferable because it can contain the target peptide and the like.
Hereinafter, although the method to manufacture a casein hydrolyzate using a proteolytic enzyme is demonstrated concretely, this technique is not limited to this.

First, a raw material (casein) is dispersed and dissolved in water.
The concentration of the lysate is not particularly limited, but it is usually preferable from the viewpoint of efficiency and operability to make the concentration range about 5 to 15% by mass in terms of protein.

Next, a raw material aqueous solution is prepared by adjusting the pH of the solution to around the optimum pH of the proteolytic enzyme to be used. Specifically, the pH of the lysis solution is preferably adjusted to pH 7 to 10 in which the optimum pH of many proteolytic enzymes is within the range using an alkaline solution.
Although the alkali agent used for pH adjustment is not specifically limited, For example, sodium hydroxide, potassium hydroxide, potassium carbonate etc. are mentioned.

Next, a proteolytic enzyme is added to the prepared raw material aqueous solution.
Examples of proteolytic enzymes include bacterial, animal and plant derived proteolytic enzymes, and any of them can be used.

The proteolytic enzyme derived from bacteria is not particularly limited. For example, as an endoprotease derived from Bacillus, Alcalase (manufactured by Novozymes), Neutase (manufactured by Novozymes), Protin A (manufactured by Daiwa Kasei), Protin P (Yamato) Kasei Co., Ltd.), Pro Leather (Amano Enzyme), Protease N (Amano Enzyme), Corolase 7089 (Higuchi Trading Co.), Bioprase (Nagase Chemtech), Orientase 90N (Hibiai) Examples include orientase 22BF (manufactured by Hibiai).
The animal-derived proteolytic enzyme is not particularly limited, and examples thereof include PTN mainly composed of trypsin (manufactured by Novozymes), trypsin V (manufactured by Nippon Biocon).
The plant-derived proteolytic enzyme is not particularly limited, and examples thereof include papain (manufactured by Amano Enzyme) and bromelain (manufactured by Amano Enzyme).
Moreover, the proteolytic enzyme mentioned above can also be used individually or in combination of 2 or more types.

Proteolytic enzyme is preferably used after being dispersed in cold water at 4 to 10 ° C. and dissolved. The concentration of the proteolytic enzyme solution is not particularly limited, but it is usually desirable from the viewpoint of efficiency and operability that the enzyme concentration is about 3 to 10%.

The amount of proteolytic enzyme used for casein hydrolysis varies depending on the substrate concentration, enzyme titer, reaction temperature, reaction time, etc., but in general, 1000 to 20000 units (activity units) per gram of protein equivalent of casein. ) Is a desirable embodiment.

The activity unit of proteolytic enzyme can be measured according to the type of proteolytic enzyme used.

When adding the proteolytic enzyme, it is desirable to dissolve and add them one by one, but the order of addition is not particularly limited.

During the enzyme reaction, the temperature of the reaction system is not particularly limited, and is selected from a range that can be put to practical use including the optimum temperature range in which the enzyme action is exhibited, and is usually selected from the range of 30 to 60 ° C.
The reaction duration varies depending on the reaction conditions such as reaction temperature and initial pH.For example, if the reaction duration of the enzyme reaction is constant, a decomposition product having different physicochemical properties may be generated for each production batch. Because there are problems, it may be difficult to make a general decision. Therefore, it is desirable to determine the duration of the reaction by monitoring the enzymatic reaction so that the physicochemical properties of the casein hydrolyzate have a desired value.
Examples of the enzyme reaction monitoring method include a method of collecting a part of the reaction solution and measuring the protein degradation rate and the like.

Next, the enzyme reaction is stopped.
The enzyme reaction is stopped by deactivating the enzyme in the hydrolyzed solution. The deactivation treatment can be performed by a conventional method such as a heat deactivation treatment.
Conditions for the heat deactivation treatment (heating temperature, heating time, etc.) can be appropriately set in consideration of the thermal stability of the enzyme used, and can be appropriately set, for example, in the temperature range of 80 to 130 ° C. In a holding time of 30 minutes to 2 seconds.

After the enzymatic reaction is stopped, the obtained hydrolytic deactivation solution is selected from the group consisting of (1) filtration, (2) microfiltration, membrane separation treatment such as ultrafiltration membrane, and (3) resin adsorption separation. It is preferable to purify by any one or a combination of two or more thereof.

By performing the above-described purification, it is possible to remove insoluble matters contained in the inactivated liquid, reduce fat, lactose, and other unnecessary components. As a result, it is possible to obtain a casein hydrolyzate that is transparent in a solution state and that does not cause turbidity, precipitation, agglomeration, browning or the like even during long-term storage in a solution state, and has excellent storage stability.

In addition, by performing the above-described purification, it is possible to improve the flavor and appearance of the casein hydrolyzate used in the present technology.

Filtration of said (1) can be implemented by a well-known method, for example, can be implemented with a well-known apparatus using diatomaceous earth.
By performing filtration, it is possible to remove the insoluble matter produced during the hydrolysis reaction and / or during the enzyme heating inactivation in the hydrolysis deactivation liquid.

The membrane separation treatment (2) can be performed using a known apparatus. Although it does not specifically limit as a well-known apparatus, For example, ultrafiltration modules etc., ultrafiltration module SEP1053 (Asahi Kasei company make, molecular weight cut off 3,000), SIP1053 (Asahi Kasei company make, molecular weight cut off 6,000), SLP1053 (Manufactured by Asahi Kasei Co., Ltd., molecular weight cut-off 10,000).
In this case, a solution containing a casein hydrolyzate is obtained as a membrane permeation fraction after membrane separation treatment.
By performing the membrane separation treatment, the insoluble matter generated during the hydrolysis reaction and / or during the enzyme heating inactivation, which is present in the hydrolysis deactivation liquid, can be removed as in the case of the filtration in (1) above.

The resin adsorption separation of (3) can be carried out by a known method, and for example, can be carried out by filling a column with resin and allowing the hydrolysis and deactivation liquid to pass through the column. The resin is not particularly limited, and examples thereof include trade names: Diaion, Sepabeads (manufactured by Mitsubishi Chemical), Amberlite XAD (manufactured by Organo), KS-35 (manufactured by Ajinomoto Fine-Techno), and the like.
Resin adsorption separation can also be performed in a continuous manner by filling these resins into a column and continuously flowing in and out of the hydrolysis deactivation liquid. Can be carried out in a batch system in which the hydrolytic deactivation liquid and the resin are separated after being put in contact for a certain period of time.
Factors that cause turbidity, precipitation, agglomeration, browning, etc. during the storage period (for example, peptides containing a large amount of hydrophobic amino acids) may remain in the hydrolyzed deactivation solution. By performing the above, these factors can be removed.

Moreover, you may sterilize the solution containing the obtained casein hydrolyzate after refinement | purification.
As the sterilization method, a conventional heat treatment method or the like can be used.
The heating temperature and holding time at the time of the heat treatment may be set appropriately under conditions for sterilization, and can be sterilized by, for example, heat treatment at 70 to 140 ° C. for 2 seconds to 30 minutes.
The heat sterilization method can be either a batch method or a continuous method, and a plate heat exchange method, an infusion method, an injection method, or the like can also be used in the continuous method.

Furthermore, the solution containing the obtained casein hydrolyzate can be used as it is, and if necessary, the solution can also be used as a concentrated solution by a known method. Further, the concentrated liquid can be dried by a known method and used as a powder.

In addition, after removing the insoluble components of the casein hydrolyzate, secondary hydrolysis may be performed by adding endoprotease or exoprotease for the purpose of improving flavor or improving physical properties.

Here, the casein hydrolyzate used in the present technology has an average molecular weight of preferably 1200 daltons or less, more preferably 1000 daltons or less, further preferably 800 daltons or less, and even more preferably 450 daltons or less. From the viewpoint of exhibiting better effects of the present technology, it is preferable to prepare a casein hydrolyzate. The average molecular weight is preferably adjusted to 250 to 450 daltons, more preferably 360 to 390 daltons.
Further, the casein hydrolyzate used in the present technology has a decomposition rate such that the lower limit is preferably 10% or more, the upper limit is preferably 40% or less, and even more preferably 20 to 30%. It is preferable to prepare a hydrolyzate from the viewpoint of exhibiting better effects of the present technology.
In the present technology, the degree of hydrolysis is adjusted so that the average molecular weight of the casein hydrolyzate contained in the filtrate after removing insolubles generated by the hydrolysis is within the target range, and / or It is preferable to determine the reaction conditions such as the reaction temperature and the reaction duration so that the decomposition rate falls within the target range.

Moreover, as a casein hydrolyzate used by this technique, the ratio of the mass sum of the free amino acid to the mass sum total of all the amino acids contained in this becomes like this. Preferably it is 15 mass% or less, More preferably, it is 10 mass% or less. Thus, it is more preferable to prepare a casein hydrolyzate from the viewpoint of exhibiting better effects of the present technology.
Further, as the casein hydrolyzate used in the present technology, the ratio of the tripeptide MKP contained therein is preferably 0.001 to 1% by mass, more preferably 0.005 to 0.5% by mass, and still more preferably. Preparation from 0.01 to 0.1% by mass is preferred from the viewpoint of efficacy and production efficiency.
In the present technology, the ratio of the total mass of free amino acids or the ratio of the tripeptide MKP is the target ratio of each, so that the type of enzyme, the amount of enzyme added, the reaction time, and / or Or it can adjust with the refinement | purification conditions (membrane separation, resin adsorption separation), etc. after a hydrolysis.

The <amino acid degradation rate>, <average molecular weight calculation method>, <amino acid release rate calculation method>, and <tripeptide MKP content measurement> in the casein hydrolyzate of the present technology will be described below.

<Method for calculating molecular weight>
The average molecular weight (Da: Dalton) of the casein hydrolyzate in the present technology is determined by the following concept of number average molecular weight.
The number average molecular weight is described in, for example, literature (edited by the Society of Polymer Science, “Basics of Polymer Science”, pages 116 to 119, Tokyo Kagaku Dojin, 1978). As shown, the average value of the molecular weight of the polymer compound is shown based on different indicators as follows.
That is, high molecular weight compounds such as protein hydrolysates are heterogeneous substances and have a distribution in molecular weight. Therefore, the molecular weight of protein hydrolysates must be expressed as an average molecular weight in order to handle them physicochemically. The number average molecular weight (hereinafter sometimes abbreviated as Mn) is an average of the number of molecules, the molecular weight of the peptide chain i is Mi, and when the number of molecules is Ni, the following formula ( Defined by 1).

<Calculation method of decomposition rate>
The degradation rate of casein hydrolyzate can be calculated by the following mathematical formula (2). The formol nitrogen amount can be determined by the formol method, and the total nitrogen amount can be determined by the Kjeldahl method.

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

(A) Measurement of amino acid composition For amino acids other than tryptophan, cysteine and methionine, the sample was hydrolyzed with 6N hydrochloric acid at 110 ° C. for 24 hours, and for tryptophan, alkaline decomposition was performed with barium hydroxide at 110 ° C. for 22 hours to obtain cysteine. And methionine are treated with formic acid, hydrolyzed with 6N hydrochloric acid at 110 ° C. for 18 hours, analyzed by an amino acid analyzer (for example, 835 type, manufactured by Hitachi, Ltd.), and the mass of the amino acid is measured.
In this method, the amount of glutamine and glutamic acid in the sample is quantified as an analytical value of glutamic acid, which is the total amount of both.

(B) Calculation of the ratio of the total mass of free amino acids Each amino acid composition in the sample is measured by the above-mentioned (a) method for measuring amino acid composition, and the total is calculated to calculate the mass of all amino acids in the sample. Next, the sample is deproteinized with sulfosalicylic acid, the mass of each remaining free amino acid is measured by the method (a) above, and the total is calculated to calculate the mass of all free amino acids in the sample. From these values, the ratio of the total mass of free amino acids in the sample is calculated by the following mathematical formula (3).

<Measurement of tripeptide MKP content>
(A) The sample powder is diluted and dissolved in a 0.2% formic acid aqueous solution so as to be 1.0 mg / mL, subjected to ultrasonic crushing for 10 minutes, and then filtered through a PVDF filter having a 0.22 μm aperture (manufactured by Millipore). A powder solution is prepared and LC / MS analysis is performed under the following measurement conditions. On the other hand, several solutions of a tripeptide MKP chemically synthesized standard peptide (manufactured by Peptide Laboratories) are prepared for each concentration, LC / MS analysis is performed under the following measurement conditions, and a calibration curve is created.
Among the peaks in the analysis of the powder solution, those having the same molecular weight and retention time as the standard peptide are identified as 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.

(B) MKP content (mg / casein hydrolyzate 1 g)
MKP content (mg / casein hydrolyzate 1 g) = [measured value of tripeptide MKP in the obtained casein hydrolyzate (mg)] / [mass of the obtained casein hydrolyzate (g)]
[Measured value of tripeptide MKP in the obtained casein hydrolyzate (mg)] is a measured value of tripeptide MKP in the sample by the following “LC / MS”.

(C) LC / MS using device Mass spectrometer: TSQ Quantum Discovery MAX (manufactured by Thermo Fisher Scientific).
High-speed liquid chromatograph: Prominence (manufactured by Shimadzu Corporation), column: XBridge BEH300 C18 φ2.1 mm × 250 mm, 3.5 μm (manufactured by Waters).

(D) LC / MS measurement conditions Mobile phase A: 0.2% by weight Formic acid-aqueous solution Mobile phase B: 0.2% by weight Formic acid-acetonitrile solution Time program: 2% B (0.0 min) -25% B ( 5.0 minutes) -65% B (5.1 minutes) -65% B (10 minutes) -85% B (10.1 minutes) -85% B (13.0%)-2% B (13. 1 minute)-STOP (30.0 minutes).
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)

2. Indigestible dextrin The indigestible dextrin used in this technology is a kind of water-soluble dietary fiber obtained from starch. For example, it can be obtained by enzymatic digestion of roasted dextrin. It may be obtained by subsequent hydrogenation.
The indigestible dextrin of the present technology is, for example, a roasted dextrin obtained by adding and / or heating a starch derived from a plant such as corn, wheat, rice, beans, potatoes, tapioca and / or heating. This is a water-soluble dietary fiber that has been subjected to enzyme treatment with α-amylase and / or glucoamylase as necessary, and then desalted and decolorized as necessary, and has indigestible characteristics. For such indigestible dextrin, high-performance liquid chromatograph, which is a method for analyzing dietary fiber, described in Hoshin No. 13 dated April 26, 1999 (“Analytical Methods for Nutritional Components, etc. in Nutrition Labeling Standards”) Dextrins containing indigestible components measured by a method (enzyme-HPLC method), preferably dextrins containing 85 to 95% by weight of indigestible components. The indigestible dextrin used in the present invention includes a reduced product of indigestible dextrin produced by hydrogenation for convenience.
Indigestible dextrin and its reduced product (reduced indigestible dextrin) are commercially available in the form of powder, fine granules, granules and the like, and any form can be used in the present technology.
In the present specification, “digestibility” of indigestible dextrin means that it is difficult to digest with human digestive enzymes.
Indigestible dextrin can be quantified by high performance liquid chromatography (enzyme-HPLC method (AOAC 2001.03)) (for example, Reference 5 (Japanese Patent Laid-Open No. 2001-252064, Reference 6 ( 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 7 (thermal denaturation and enzymatic action of starch-difficult Characteristics of digestible dextrins, Kazuhiro Otsuki, Isao Matsuda, Yasuo Katsuta, Takao Hanno, Starch Science (Denpun kagaku) Vol.37 No.2 p107-114 (1990)), Reference 8 (difficulty from roasted dextrins) Preparation of digestible dextrin, Kazuhiro Otsuki, Isao Matsuda, J. Appl. Glycosci., Vol.50 No.3 p389-394 (2003)).

Indigestible dextrin is a low-calorie, low-fat food material that has physiological activities such as intestinal regulation, blood glucose elevation-inhibiting, serum cholesterol-lowering, intestinal environment improvement, and neutral fat-lowering. (For example, Reference 9 (Japanese Patent Laid-Open No. 2001-252064), Reference 10 (H04-91765), etc.).
Moreover, as a manufacturing method of indigestible dextrin, for example, reference 9 and reference 10 can be referred to. Starch that is a raw material of the hardly digestible dextrin is not particularly limited, and for example, starch such as corn, potato, sweet potato, tapioca, wheat, barley, rice, etc. can be used, among which corn starch is preferred. In addition, examples of the mineral acid when acidifying include hydrochloric acid, nitric acid, sulfuric acid, and the like, among which hydrochloric acid is preferable.

3. Uses of casein hydrolyzate and indigestible dextrin of this technology As shown in [Examples] below, the casein hydrolyzate and indigestible dextrin of this technology were not effective alone when used in combination. It has a preventive effect on stroke, a delay effect, or a life-prolonging effect (hereinafter also referred to as “stroke preventive effect etc.”). Moreover, the casein hydrolyzate and indigestible dextrin of the present technology can be used for the purpose of prevention, delay, or prolongation of life against stroke.
Therefore, the casein hydrolyzate and indigestible dextrin of the present technology can be contained as an active ingredient in a composition or preparation for stroke prevention, and used for various uses such as pharmaceuticals, foods and drinks, and feeds. Alternatively, it may be a material or a preparation used by blending with these foods and drinks.
The casein hydrolyzate and indigestible dextrin of the present technology can be used as they are for animals including humans, or they can be used as usual food- or pharmaceutically-acceptable carriers or It can also be used by mixing with a diluent. Thereby, this technique can exhibit the various effects mentioned above.
Moreover, the casein hydrolyzate and indigestible dextrin of this technique can be used for manufacture of these various compositions or formulations.

In this specification, a stroke is a disease caused by clogging or rupture of blood vessels in the brain. Examples of stroke include cerebral infarction, cerebral hemorrhage, subarachnoid hemorrhage, transient ischemic attack Cerebral thrombosis, cerebral embolism and the like. In general, stroke may be divided into early symptoms and symptoms after the middle phase (cerebral infarction, cerebral hemorrhage, etc.). From the viewpoint of preventing an event from becoming large, emphasis is placed on preventing or responding to early symptoms. Yes.
In the present specification, the initial symptoms of stroke include the occurrence of a transient cerebral ischemic attack, and as a symptom of the transient cerebral ischemic attack, specifically, a mild language disorder (Lu Ritsu does not turn, words do not come out, can not understand), mild pain (one limb, paralysis / numbness of half face), mild behavioral disorder (cannot stand, cannot walk, flutter etc.) ), Minor visual impairments (things appear to be two, half of the visual field is missing, one eye is not visible, etc.).
Moreover, this embodiment may be used for therapeutic purposes or may be used for non-therapeutic purposes.
“Non-therapeutic purpose” is a concept that does not include medical practice, that is, treatment of the human body by treatment. For example, health promotion, beauty acts and the like can be mentioned.
“Improvement” refers to improvement of a disease, symptom or condition; prevention, delay of worsening of the disease, symptom or condition; reversal, prevention or delay of progression of the disease or symptom.
“Prevention” refers to prevention or delay of the onset of a disease or symptom in the application subject, or a reduction in the risk of the disease or symptom to be applied.

The casein hydrolyzate and indigestible dextrin according to the present technology, and the composition for preventing stroke (hereinafter also referred to as “composition etc.”) are used for pharmaceuticals, foods and drinks using their excellent efficacy effects. Or feed (preferably pet food).

The casein hydrolyzate and indigestible dextrin used in the present technology are suitable for oral intake because they are easily soluble in water and have excellent processing stability.

The form of the composition of the present technology is not particularly limited, and a tablet such as a powder or a granule, a tablet that has been compressed, or a capsule filled in a capsule is preferable.
Moreover, the composition of this technique may consist of unit packaging forms. The composition composed of the unit packaging form only needs to contain the two components of the present technology as a unit packaging. For example, a preparation containing casein hydrolyzate and a preparation containing indigestible dextrin are separated. It may be unit-packed in the form of a preparation or composition, or may be unit-packed in a form in which the two components of the present technology are mixed together in a powdery state or the like. From the viewpoint of convenience, a unit packaging form per meal is preferred.

The content or use amount of the casein hydrolyzate used in the composition or the like according to the present technology can be freely set according to age, symptoms, and the like as long as the efficacy of the present technology is not impaired.
In the present technology, the content of casein hydrolyzate can be set to 0.001 to 1% by mass with respect to the final composition.
In the present technology, the content of the tripeptide MKP can be set to 0.00001 to 0.005 mass% with respect to the final composition.
As used herein, the final composition refers to a composition when administered to a subject or taken by a subject.
In the present technology, the amount of casein hydrolyzate used for the 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 still more preferably 0. 0.001 to 0.1 g / kg body weight / day.

The content or use amount of the indigestible dextrin used in the present technology can be freely set according to the age, symptoms and the like as long as the efficacy of the present technology is not impaired.
In the present technology, for example, when the amount of indigestible dextrin per serving is about 5 g, the content of indigestible dextrin can be set to 1 to 10% by mass with respect to the final composition.
In the present technology, the amount of indigestible dextrin used for the subject is preferably 0.001 to 10 g / kg body weight / day, more preferably 0.005 to 5 g / kg body weight / day, and still more preferably 0.01. ~ 1 g / kg body weight / day.

The individual content or use amount of casein hydrolyzate and indigestible dextrin in the present technology is not particularly limited, but the proportion of these content or use amount is from the viewpoint of exhibiting better effects of the present technology. Indigestible dextrin: casein hydrolyzate = 10: 0.001 to 1: 1, preferably indigestible dextrin: casein hydrolyzate = 1: 0.001 to 10: 1 It is more preferable to contain.
Further, in the present technology, the individual content or use amount of the tripeptide MKP: indigestible dextrin is not particularly limited, but from the viewpoint of exerting better effects of the present technology, with respect to 1 part by mass of the tripeptide MKP, The lower limit value of the indigestible dextrin is preferably 5000 parts by mass or more, more preferably 10,000 parts by mass or more, and the upper limit value thereof is preferably 100,000 parts by mass or less, more preferably 80000 parts by mass or less. Is preferably 15000 to 50000 parts by mass of indigestible dextrin.

In the present technology, casein hydrolyzate and indigestible dextrin can be used at the same time or separately as long as the efficacy of the present technology is not impaired.
In addition, the use interval (specifically, administration or intake interval) of the present technology is not particularly limited, and may be once a day or may be divided into a plurality of times. Moreover, it is desirable to use this technique continuously every day (specifically, administer or ingest).
In addition, the casein hydrolyzate and the indigestible dextrin used in the present technology are empirically safe and can be taken continuously for a long time. This technology is superior in terms of being able to continuously demonstrate the preventive effect of this technology by continuously using it for a long period of time, and it is desirable to use it continuously every day, for example, using it for 30 days or more. It is done.

In addition, the present technology preferably starts administration or ingestion before the symptoms of stroke appear, and preferably administers or ingests before the appearance of the initial symptoms of stroke (for example, a transient ischemic attack). It is desirable to start. In addition, even if the initial symptom of a stroke has appeared, this technique can prevent the symptom after the said middle stage by starting administration or ingestion before the symptom after the middle stage appears.

The subject of the present technology is not particularly limited, and may be a human or a non-human animal. In addition, the two ingredients of the present technology are safe and can be ingested for a long period of time. The subject of the present technology is preferably a person who wants to reduce the risk of stroke, a person who is likely to have a risk of stroke, or a person who has a high risk from the viewpoint of stroke prevention.

<Pharmaceuticals and quasi drugs>
This technology uses its excellent efficacy and effects as an active ingredient in human or veterinary drugs, quasi-drugs (hereinafter also referred to as “pharmaceuticals”) for use in the prevention of stroke. It can be used in combination.

When blended with a pharmaceutical or the like, the pharmaceutical can be appropriately formulated into a desired dosage form according to an administration method such as oral administration or parenteral administration. The dosage form is not particularly limited, but for oral administration, for example, solid preparations such as powders, granules, tablets, troches and capsules; liquid preparations such as solutions, syrups, suspensions and emulsions. Can be In the case of parenteral administration, it can be formulated into, for example, suppositories, sprays, inhalants, ointments, patches, injections and the like. In this technique, it is preferable to formulate into a dosage form for oral administration.
The formulation can be appropriately performed by a known method depending on the dosage form.

In the formulation, it may be formulated by appropriately blending a formulation carrier. In addition to the peptides of the present technology, components such as excipients, pH adjusters, colorants, and corrigents that are commonly used for formulation can be used. Furthermore, a component having an effect of preventing, ameliorating and / or treating a known or future disease or symptom can be used in combination according to the purpose.

As the preparation carrier, various organic or inorganic carriers can be used depending on the dosage form. Examples of the carrier in the case of a solid preparation include excipients, binders, disintegrants, lubricants, stabilizers, and flavoring agents.

Examples of the excipient include sugar derivatives such as lactose, sucrose, glucose, mannitol and sorbit; starch derivatives such as corn starch, potato starch, α-starch, dextrin and carboxymethyl starch; crystalline cellulose and hydroxypropylcellulose Cellulose derivatives such as hydroxypropylmethylcellulose, carboxymethylcellulose, carboxymethylcellulose calcium; gum arabic; dextran; pullulan; silicate derivatives such as light anhydrous silicic acid, synthetic aluminum silicate, magnesium magnesium magnesium silicate; phosphate derivatives such as calcium phosphate; Examples thereof include carbonate derivatives such as calcium carbonate; sulfate derivatives such as calcium sulfate.

Examples of the binder include gelatin, polyvinyl pyrrolidone, macrogol and the like in addition to the excipients described above.

Examples of the disintegrant include, in addition to the above excipients, chemically modified starch or cellulose derivatives such as croscarmellose sodium, carboxymethyl starch sodium, and crosslinked polyvinylpyrrolidone.

Examples of the lubricant include talc; stearic acid; stearic acid metal salts such as calcium stearate and magnesium stearate; colloidal silica; waxes such as pea gum and gallow; boric acid; glycol; carboxyl such as fumaric acid and adipic acid Acids; sodium carboxylic acid 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; starch derivatives, etc. Can be mentioned.

Examples of the stabilizer include paraoxybenzoates such as methylparaben and propylparaben; alcohols such as chlorobutanol, benzyl alcohol and phenylethyl alcohol; benzalkonium chloride; acetic anhydride; sorbic acid and the like.

Examples of the flavoring agent include sweeteners, acidulants, and fragrances.
In addition, as a carrier used in the case of a liquid for oral administration, a solvent such as water, a flavoring agent and the like can be mentioned.

The content of casein hydrolyzate used in the pharmaceuticals and the like according to the present technology can be freely set according to age, symptoms, etc., as long as the effects of the present technology are not impaired. In the present technology, in particular, the content of casein hydrolyzate can be set to 0.001 to 1% by mass with respect to the final composition such as a pharmaceutical product.
In the present technology, the amount of casein hydrolyzate used for the 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 still more preferably 0. 0.001 to 0.1 g / kg body weight / day.

In addition, the content of indigestible dextrin used in pharmaceuticals and the like according to the present technology can be freely set according to age, symptoms, etc., as long as the effects of the present technology are not impaired. In the present technology, for example, when the amount of indigestible dextrin per serving is about 5 g, the content of indigestible dextrin may be set to 1 to 10% by mass with respect to the final composition such as a pharmaceutical product. it can. In the present technology, the amount of indigestible dextrin used for the subject is preferably 0.001 to 10 g / kg body weight / day, more preferably 0.005 to 5 g / kg body weight / day, and still more preferably 0.01. ~ 1 g / kg body weight / day.

Thus, in the composition provided in the form of a pharmaceutical or the like, the individual content or use amount of the indigestible dextrin and casein hydrolyzate is not particularly limited, but as a ratio of these content or use amount Is preferably contained in a mass ratio of indigestible dextrin: casein hydrolyzate = 10: 0.001 to 1: 1 from the viewpoint of exhibiting better efficacy of the present technology. Dextrin: casein hydrolyzate is more preferably contained in a ratio of 1: 0.001 to 10: 1.
Further, in the present technology, the individual content or use amount of the tripeptide MKP: indigestible dextrin is not particularly limited, but from the viewpoint of exerting better effects of the present technology, with respect to 1 part by mass of the tripeptide MKP, The lower limit value of the indigestible dextrin is preferably 5000 parts by mass or more, more preferably 10,000 parts by mass or more, and the upper limit value thereof is preferably 100,000 parts by mass or less, more preferably 80000 parts by mass or less. Is preferably 15000 to 50000 parts by mass of indigestible dextrin.

<Food &Drink>
This technology makes use of its excellent efficacy and effects, food or drink for humans or animals, health food, functional food, food for the sick, enteral nutrition food, special-purpose food for use in the prevention of stroke, As an active ingredient of functional health foods, foods for specified health use, functional labeling foods that are useful for preventing strokes, functional nutritional foods (hereinafter also referred to as “food and beverages”), etc. Can be used.

This technique can be prepared by adding to a known food or drink, or can be mixed with a raw material of a food or drink to produce a new food or drink.

The foods and drinks are not limited to liquids, pastes, solids, powders, and the like, and in addition to tablet confections, liquid foods, feeds (including for pets), etc., for example, flour products, instant foods, processed agricultural products, Processed marine products, processed livestock products, milk / dairy products, fats and oils, basic seasonings, compound seasonings / foods, frozen foods, confectionery, beverages, and other commercial products.

Examples of the flour product include bread, macaroni, spaghetti, noodles, cake mix, fried flour, bread crumbs and the like.
Examples of the instant foods include instant noodles, cup noodles, retort / cooked food, cooking canned food, microwave food, instant soup / stew, instant miso soup / soup, canned soup, freeze-dried food, other instant foods, etc. Can be mentioned.
Examples of the processed agricultural products include canned agricultural products, canned fruits, jams and marmalades, pickles, boiled beans, dried agricultural products, and cereals (cereal processed products).
Examples of the processed fishery products include canned fishery products, fish hams and sausages, fishery paste products, fishery delicacies, and tsukudani.
Examples of the processed livestock products include canned livestock products / pastes, livestock meat hams / sausages, and the like.
Examples of the milk / dairy products include processed milk, milk beverages, yogurts, lactic acid bacteria beverages, cheese, ice creams, prepared milk powders, creams, and other dairy products.
Examples of the fats and oils include butter, margarines, and vegetable oils.
Examples of the basic seasonings include soy sauce, miso, sauces, tomato processed seasonings, mirins, vinegars, etc., and the mixed seasonings and foods include cooking mixes, curry ingredients, and sauces , Dressings, noodle soups, spices, and other complex seasonings.
As said frozen food, raw material frozen food, semi-cooked frozen food, cooked frozen food, etc. are mentioned, for example.
Examples of the confectionery include caramel, candy, chewing gum, chocolate, cookies, biscuits, cakes, pie, snacks, crackers, Japanese confectionery, rice confectionery, bean confectionery, dessert confectionery, and other confectionery.
Examples of the beverage include carbonated beverages, natural fruit juices, fruit juice beverages, soft drinks with fruit juice, fruit beverages, fruit beverages with fruit granules, vegetable beverages, soy milk, soy milk beverages, coffee beverages, tea beverages, powdered beverages, and concentrated beverages. Sports drinks, nutritional drinks, alcoholic drinks, other taste drinks, and the like.
Examples of commercially available foods other than the above include baby food, sprinkles, and green tea paste.

[Method of manufacturing food and drink of the present technology]
The food and drink etc. of this technology can be manufactured by adding casein hydrolyzate and indigestible dextrin to the raw material of the food and drink composition, and adding the casein hydrolyzate and indigestible dextrin Except for the above, it can be produced in the same manner as a normal food and drink composition. Addition of the casein hydrolyzate and indigestible dextrin of the present technology may be performed at any stage of the production process of the food or drink composition.
The foods and drinks of this technology can be added with good bacteria, and among the foods and drinks containing good bacteria, the probiotic effect by fermentation of good bacteria can be added. It is.
In the method for producing a fermented food or drink, casein hydrolyzate and indigestible dextrin may be added at any stage of the production process. For example, fermented foods and drinks may be manufactured through the fermentation process containing these as raw materials. Examples of such foods and beverages include lactic acid bacteria beverages and fermented milk.

[Fermented food and drink of this technology and method for producing the same]
Although the manufacturing method of the fermented food / beverage products of this technique is demonstrated below, it is not limited to this.
The manufacturing method of fermented food / beverage products of this technique can use a casein hydrolyzate and an indigestible dextrin as a raw material of fermented food / beverage products. The casein hydrolyzate and / or indigestible dextrin of the present technology can be used both before and / or after the fermentation step of the fermented food or drink.

In addition, the raw material used for the manufacturing method of this technique is a raw material which may be used in any process of the manufacturing method of fermented milk unless there is particular limitation, and is used as a raw material for pre-fermentation and / or post-fermentation. May be.
As the raw material, it is preferable to use one or more selected from the group consisting of a low-calorie sweetener, a rare monosaccharide, and a milk oligosaccharide from the viewpoint of more suitably exerting the efficacy of the present technology. .
As the raw material, it is preferable to use a low calorie sweetener and / or a rare sugar because of improving the flavor, and it is more preferable to use a low calorie sweetener and a rare sugar in combination.
As a raw material, milk oligosaccharide (preferably lactulose) is used from the viewpoints of imparting milk flavor, reaching the large intestine without being decomposed and absorbed and becoming an assimilation component of bifidobacteria and promoting absorption of calcium and magnesium. It is preferable to use it.
The content of the low calorie sweetener is preferably 0.001 to 0.1% by mass in the final product.
The content of the rare sugar is preferably 0.005 to 0.25% by mass in the final product.
The content of the lactulose is preferably 0.5 to 6% by mass in the final product.

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, and the like. You may use goods. One or two or more selected from the group consisting of these can be selected, and sucralose is preferred.
Examples of the rare monosaccharides include D-psicose and D-allose, and commercially available products may be used. Examples of the commercially available products include rare sugar-containing syrup (rare sugar sweet (manufactured by Matsutani Chemical Industry Co., Ltd.)). ). Of these, D-psicose and / or D-allose are preferred, and the combined use of D-psicose and D-allose is more preferred.
It contains lactulose, and a commercially available product may be used. Examples of the commercially available product include milk oligosaccharides MLC-90, MLP-95, MLS-95 (manufactured by Morinaga Milk Industry Co., Ltd.) and the like. The milk oligosaccharide preferably contains lactulose in an amount of 30% by mass or more, more preferably 40% by mass or more, and still more preferably 50% by mass or more.

Hereinafter, the casein hydrolyzate and indigestible dextrin will be described with an example when used as a raw material before fermentation, but the method for producing a fermented food or drink of the present technology of the present technology is not limited thereto. Absent.
In the production method of the present technology, a milk preparation containing a casein hydrolyzate and an indigestible dextrin as a raw material for fermented milk can be sterilized, and fermented bacteria can be added to the sterilized milk preparation and fermented until the pH is 5.0 or lower. .
It is preferable to ferment by adding a lactic acid bacteria starter and / or a Bifidobacterium bacterium as the fermentation bacteria.

As a raw material for fermented milk used in the present technology, a general raw material for fermented milk can be used except that a casein hydrolyzate and an indigestible dextrin are blended.
As a general fermented milk raw material, it is not particularly limited as long as it includes a raw material derived from milk and capable of producing a fermented food or drink by fermenting using fermenting bacteria, and milk or a fraction thereof Products or processed products (for example, milk, skim milk, fresh cream, butter, whole milk powder, skim milk powder, or a mixture, solution, or suspension of these in water). Milk is not particularly limited in animal origin, but is preferably derived from cattle.
As the fermented milk material, optional components such as sweeteners such as sucrose, pectin, fruit, fruit juice, agar, gelatin, fats and oils, fragrances, coloring agents, stabilizers, reducing agents and the like may be blended as necessary.
The fermented milk raw material may be sterilized, homogenized, cooled, etc. according to a conventional method before fermentation.

Fermentation bacteria containing a lactic acid bacteria starter and / or a Bifidobacterium genus may be added to the fermented milk raw material (preferably milk preparation) for fermentation. Any of these fermenting bacteria may be inoculated multiple times.

The “lactic acid bacteria starter” inoculated into the fermented milk raw material may be a single strain or a combination of a plurality of strains.
The “lactic acid bacteria starter” in the present technology is not particularly limited as long as it is used for the production of food and drink. Examples of the “lactic acid bacteria starter” include, for example, when the fermented food or drink is yogurt, Lactobacillus bulgaricus, Lactobacillus delbruecki subspecies bulgaricus, Streptococcus thermophilus, and the like. A single strain may be used, or a combination of a plurality of strains may be used.

The inoculation amount of the fermented bacteria of the present technology to the fermented milk raw material is not particularly limited.
The lactic acid bacteria and Bifidobacterium bacteria of the present technology are preferably 10 ⁴ to 10 ⁹ CFU / mL milk raw material, more preferably 10 ⁶ to 10 ⁸ CFU / mL milk raw material.
The Bifidobacterium is preferably 10 ⁵ to 10 ⁹ CFU / mL milk material, more preferably 10 ⁷ to 10 ⁸ CFU / mL milk material.

Bifidobacterium and / or other lactic acid bacteria inoculated into the fermented milk raw material are preferably seeded or pre-cultured in another medium in advance.
The medium used before the main culture is not particularly limited as long as it is a medium suitable for culturing Bifidobacterium and / or other lactic acid bacteria, and examples thereof include a medium containing reduced skim milk powder.
The concentration of the reduced skim milk powder is preferably 3% (W / W) or more, and particularly preferably 8% (W / W) or more. In addition, a growth promoting substance 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 Bifidobacterium is used, it contains a growth promoting substance, for example, 0.1 to 1% (W / W) yeast extract because of low growth in a medium containing reduced skim milk powder. It is preferable to use a medium. The sterilization conditions for the medium are the same as described above.

In the method for producing a fermented food / beverage product according to the present technology, the fermentation conditions such as the culture temperature and the culture time can be the same as those used for producing a normal fermented food / beverage product. 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 usually 4 to 18 hours are preferable.

</ RTI> The fermented food and drink obtained by the method for producing fermented food and drink according to the present technology can be appropriately processed in the same manner as normal fermented food and drink. For example, the fermented food or drink after fermentation may be used as it is, or may be homogenized and processed into a liquid form. Furthermore, sweeteners such as sucrose, pectin, fruit, fruit juice, agar, gelatin, fats and oils, fragrances, coloring agents, stabilizers, reducing agents and the like may be added. Moreover, you may fill a container with fermented food-drinks suitably.

The fermented foods and drinks obtained above contain casein hydrolysates and indigestible dextrins, and thereby the effects of the present technology can be exhibited well.

[Functional indication food and drink]
In addition, foods and beverages and the like defined in the present technology can be provided and sold as foods and beverages displaying specific uses (particularly health uses) and functions.
The “display” act includes all acts for informing the consumer of the use, and if the expression can remind the user of the use, the purpose of the display, the content of the display, the display Regardless of the target object / medium, etc., all fall under the “display” act of this technology.

In addition, it is preferable that the “display” is performed by an expression that allows the consumer to directly recognize the use. Specifically, it is the act of transferring, displaying, importing, displaying, or importing products that are related to food or drinks or products that describe the use, on advertisements, price lists, or transaction documents. For example, an act of describing and displaying the above uses or distributing them, or describing the above uses in information including the contents and providing them by an electromagnetic (Internet or the like) method can be given.

On the other hand, the display content is preferably a display approved by the government or the like (for example, a display that is approved based on various systems determined by the government and is performed in a mode based on such approval). Moreover, it is preferable to attach such display contents to advertising materials at sales sites such as packaging, containers, catalogs, pamphlets, POPs, and other documents.

“Indications” include health foods, functional foods, foods for the sick, enteral nutritional foods, special purpose foods, health functional foods, foods for specified health use, functional labeling foods, nutritional functional foods, and pharmaceutical departments. The display as a foreign article etc. is also mentioned. Among these, in particular, indications approved by the Consumer Affairs Agency, for example, indications approved by food systems for specific health use, functional indication food systems, systems similar to these, and the like. More specifically, indication as food for specified health use, indication as conditional health food, indication as functional indication food, indication to affect body structure and function, indication of reduced disease risk, etc. Can be mentioned. A typical example of this is the indication of food for specified health use (particularly indication of health use) as stipulated in the Enforcement Regulations of the Health Promotion Act (Ministry of Health, Labor and Welfare Ordinance No. 86 of April 30, 2003) This is a display as a functional indication food defined by the Food Labeling Act (Act No. 70 of 2013) and a similar indication.

The content of the casein hydrolyzate used for food and drink according to the present technology can be freely set according to age, symptoms, etc., as long as the effects of the present technology are not impaired. In the present technology, in particular, the content of the casein hydrolyzate can be set to 0.001 to 1% by mass with respect to the final composition such as food or drink.
In the present technology, the amount of casein hydrolyzate used for the 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 still more preferably 0. 0.001 to 0.1 g / kg body weight / day.

In addition, the content of indigestible dextrin used in foods and drinks and the like according to the present technology can be freely set according to age, symptoms, and the like as long as the effects of the present technology are not impaired. In the present technology, for example, when the amount of indigestible dextrin per serving is about 5 g, the content of indigestible dextrin is set to 1 to 10% by mass with respect to the final composition of food or drink. Can do.
In the present technology, the amount of indigestible dextrin used for the subject is preferably 0.001 to 10 g / kg body weight / day, more preferably 0.005 to 5 g / kg body weight / day, and still more preferably 0.01. ~ 1 g / kg body weight / day.

Thus, the composition provided in the form of food and drink, etc., the individual content of the indigestible dextrin and casein hydrolyzate is not particularly limited, but as the ratio of these content or use amount, From the viewpoint of exhibiting better effects of the present technology, it is preferably contained in a mass ratio of indigestible dextrin: casein hydrolyzate = 10: 0.001 to 1: 1, and indigestible dextrin: casein More preferably, the hydrolyzate is contained in a ratio of 1: 0.001 to 10: 1.
Further, in the present technology, the individual content or use amount of the tripeptide MKP: indigestible dextrin is not particularly limited, but from the viewpoint of exerting better effects of the present technology, with respect to 1 part by mass of the tripeptide MKP, The lower limit value of the indigestible dextrin is preferably 5000 parts by mass or more, more preferably 10,000 parts by mass or more, and the upper limit value thereof is preferably 100,000 parts by mass or less, more preferably 80000 parts by mass or less. Is preferably 15000 to 50000 parts by mass of indigestible dextrin.

<Feed>
The present technology can be used as an active ingredient of animal feed for use in preventing strokes by utilizing its excellent effect. The present technology can be prepared by adding to a known feed, or a new feed can be produced by mixing in a feed raw material.

Examples of raw materials for the feed include cereals such as corn, wheat, barley, and rye; bran such as bran, wheat straw, rice bran, and defatted rice bran; production of corn gluten meal, corn jam meal, and the like; Animal feeds such as fish meal and bone meal; yeasts such as beer yeast; mineral feeds such as calcium phosphate and calcium carbonate; fats and oils; amino acids; In addition, examples of the form of the feed include pet animal feed (pet food, etc.), livestock feed, fish feed, and the like.

The content of the casein hydrolyzate used in the feed according to the present technology can be freely set according to body weight, symptoms, etc., as long as the effects of the present technology are not impaired. In the present technology, in particular, the content of casein hydrolyzate 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 hydrolyzate 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 still more preferably 0.0001 to 0. .1 g / kg body weight / day.

In addition, the content of indigestible dextrin used in the feed according to the present technology can be freely set according to body weight, symptoms, and the like as long as the effects of the present technology are not impaired. In the present technology, for example, when the amount of indigestible dextrin per serving is about 5 g, the content of indigestible dextrin can be set to 1 to 10% by mass with respect to the final composition of the feed. .
In the present technology, the amount of indigestible 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 still more preferably 0.01 to 1 g / kg. Weight / day.

Thus, the composition provided in the form of feed is not particularly limited in individual content or use amount of the indigestible dextrin and casein hydrolyzate, but as a ratio of these content or use amount From the viewpoint of exhibiting better effects of the present technology, it is preferably contained in a mass ratio of indigestible dextrin: casein hydrolyzate = 10: 0.001 to 1: 1. : Casein hydrolyzate = 1 to 0.001 to 10: 1 is more preferable.
Further, in the present technology, the individual content or use amount of the tripeptide MKP: indigestible dextrin is not particularly limited, but from the viewpoint of exerting better effects of the present technology, with respect to 1 part by mass of the tripeptide MKP, The lower limit value of the indigestible dextrin is preferably 5000 parts by mass or more, more preferably 10,000 parts by mass or more, and the upper limit value thereof is preferably 100,000 parts by mass or less, more preferably 80000 parts by mass or less. Is preferably 15000 to 50000 parts by mass of indigestible dextrin.

In addition, this technique can also employ | adopt the following structures.
[1]
A composition for preventing stroke, comprising casein hydrolyzate and indigestible dextrin.
[2]
A method for preventing stroke, comprising administering or ingesting a casein hydrolyzate and an indigestible dextrin.
[3]
Casein hydrolyzate and indigestible dextrin used for the prevention of stroke, or use thereof.
[4]
Use of casein hydrolyzate and indigestible dextrin for the manufacture of a composition for preventing stroke.
[5]
Preferably, use of casein hydrolyzate and indigestible dextrin used for preventing the onset of early symptoms of stroke.

[6]
Preferably, the casein hydrolyzate according to any one of [1] to [5] includes a peptide consisting of Met-Lys-Pro.
[7]
Preferably, in any one of [1] to [6], the indigestible dextrin and casein hydrolyzate are contained in a mass ratio of 10: 0.001 to 1: 1.
[8]
Preferably, the casein hydrolyzate according to any one of [1] to [7] includes a peptide composed of the Met-Lys-Pro. More preferably, it is 5000 to 100,000 parts by mass of indigestible dextrin with respect to 1 part by mass of the peptide.
[9]
Preferably, any one of the above [1] to [8] is used for preventing an initial symptom of stroke.
[10]
Preferably, in any one of the above [1] to [9], it is for pharmaceuticals or foods and drinks.
[11]
Preferably, in any one of the above [1] to [9], the composition is for fermented foods and drinks.
[12]
Preferably, in any one of the above [1] to [11], the unit packaging form is used.
[13]
Preferably, any one of the above [1] to [12] is a powder or granule, a tablet characterized by filling a tablet or capsule, or these are used.
[14]
Preferably, in any one of the above [1] to [13], the casein hydrolyzate is contained in an amount of 0.001 to 1% by mass based on the mass of the final composition.
[15]
Preferably, in any one of the above [1] to [14], the indigestible dextrin is contained in an amount of 1 to 10% by mass based on the mass of the final composition.
[16]
A method for suppressing stroke, a method for preventing stroke, or a method for treating stroke, or a method for preventing cerebral infarction, cerebral hemorrhage, or edema, using the composition according to any one of [1] to [15].

Hereinafter, the present technology will be described in more detail based on examples. In addition, the Example described below shows an example of a typical example of the present technology, and the scope of the present technology is not interpreted narrowly.

[Production Example 1]
Add 900 mg of water to 100 mg of commercially available casein (made by New Zealand Daily Board), disperse well, adjust the pH of the solution to 7.0 by adding sodium hydroxide, completely dissolve casein, concentration about 10% A casein aqueous solution was prepared.
The aqueous casein solution was sterilized by heating at 85 ° C. for 10 minutes, adjusted to 50 ° C., sodium hydroxide was added to adjust the pH to 9.0, pancreatin 2 mg (manufactured by Amano Enzyme), protease A 4 mg ( The Amano Enzyme Co.) was added to start the hydrolysis reaction. After 8 hours, the enzyme reaction was stopped by heating at 80 ° C. for 6 minutes to stop the enzyme reaction and cooled to 10 ° C.
This hydrolyzed solution was ultrafiltered with an ultrafiltration membrane (manufactured by Nippon Pall Co., Ltd.) having a fractional molecular weight of 1000, concentrated and freeze-dried to obtain 85 mg of casein degradation product.

As a result of carrying out a plurality of lots of the above steps, the casein hydrolyzate had a degradation rate of 20 to 30%, an average molecular weight of 800 Da or less, an amino acid release rate of 10% or less, and a tripeptide MKP of 0.01 to 0.1% by mass. . These were calculated by the above-mentioned <Amino acid degradation rate>, <Average molecular weight calculation method>, <Amino acid release rate calculation method>, and <Tripeptide MKP content measurement>. The casein hydrolyzate can be prepared to have an average molecular weight of 360 to 390 Da.

[Example 1]
In the Examples, stroke-prone hypertensive spontaneously hypertensive rats (SHRSP rats) were used as animals for observing the effects on stroke. SHRSP rats are known to spontaneously develop stroke.
In this example, the effect of preventing the stroke by the combined use of casein hydrolyzate and indigestible dextrin in SHRSP rats was examined.

(1) Sample preparation Test sample 1 containing 0.1% by mass of casein hydrolyzate with respect to SP feed (manufactured by Funabashi Farm Co., Ltd.); indigestible dextrin (fiber sol 2 (derived from corn): Matsutani Test sample 2 containing 1% by mass of Chemical Industries Co., Ltd .; 0.1% by mass of casein hydrolyzate alone, and 1% of indigestible dextrin (Matsuya Chemical Co., Ltd.) alone % Of each test sample 3 was prepared. In addition, SP feed was used as a control sample.
SP feed; moisture 8.0 g; crude protein 20.8 g; crude lipid 4.8 g; crude fiber 3.2 g; ash 5.0 g; soluble nitrogen free 58.2 g.

(2) Test method SHRSP / Izm and WKY / Izm (non-pathological control) were purchased from Nippon SLC at the age of 5 weeks. Both SHRSP / Izm rats and WKY / Izm rats were preliminarily raised for 1 week at Labo MR Stock (Nippon Agricultural Industry Co., Ltd.), then WKY / Izm rats (10 rats) were fed SP diet, and SHRSP / Izm rats were divided into 10 groups, 4 groups in total, 1 group was given control samples, and the remaining 4 groups were given test sample 1, test sample 2 or test sample 3 respectively and were raised for 26 weeks . The test groups are shown in Table 1.
The survival days during the breeding period were compared, and the effect of the test sample on the prevention of stroke was evaluated.

(3) Test results Table 2 shows the number of survivors in each group 150 days after the start of breeding. In addition, Table 3 shows the test results of the difference in survival rate between groups. The survival function was estimated by the Kaplan-Meier method, and the significance probability was calculated by the generalized Wilcoxon test.

As shown in Tables 1 to 3, neither casein hydrolyzate nor indigestible dextrin alone had a life-prolonging effect on stroke. On the other hand, it was found that the group to which the test sample 3 was given compared with the control group had an extremely long survival time. Surprisingly, it has been found that casein hydrolyzate also has a life-prolonging effect on stroke which was not effective by itself when used together with indigestible dextrin.
From the above results, it was found that casein hydrolyzate also has an effect of preventing stroke by using indigestible dextrin together. Thus, the present technology can be used for prevention of stroke or delay of onset.

[Production Example 1]
Mixing casein hydrolyzate and indigestible dextrin of Production Example 1 with sucralose (manufactured by San-Eigen F.F.) and rare monosaccharide (trade name: Rare Sugar Sweet (manufactured by Matsutani Chemical Industry Co., Ltd.)) (B) milk fat 3.5 mass% or less, (C) carbohydrate 5.0 mass% or more, and (D) calcium 0.15 mass% or more. Prepare the formula as follows.
A mixture in which the milk preparation, lactic acid bacteria and bifidobacteria are uniformly mixed is fermented. As a result, a composition for preventing stroke (fermented milk) containing a casein hydrolyzate and an indigestible dextrin is obtained. The fermented milk includes (E) 0.3 to 0.8% by mass of the casein hydrolyzate of Example 1, (F) 4 to 8% by mass of indigestible dextrin, and (G) 0.05 to 0. 02 mass%, (H) D-psicose and D-allose 0.05 to 0.1 mass%, and (I) lactulose 1 to 4 mass%.
The daily intake of casein hydrolyzate and indigestible dextrin is 0.0001 to 1 g / kg body weight / day and 0.001 to 10 g / kg body weight / day indigestible dextrin, respectively. The fermented milk for stroke prevention of this technology is continuously taken every day. Thereby, the stroke prevention effect can be expected.

[Formulation Example 1: Stroke prevention powder]
Each component (powder) shown in Table 4 is mixed to obtain a stroke prevention powder. The powder can be used as a supplement, and can be made into a beverage by mixing with water. Moreover, the said powder can be used as the capsule for stroke prevention by filling or encapsulating a capsule cell. The powder can be made into a tablet for preventing stroke by compression molding. The powder can be expected to prevent stroke. In addition, the casein hydrolyzate and indigestible dextrin of manufacture example 1 can be used as a raw material of the said powder.

Claims (11)

1. A composition for preventing stroke, comprising casein hydrolyzate and indigestible dextrin.
2. The composition according to claim 1, wherein the casein hydrolyzate contains a peptide consisting of Met-Lys-Pro.
3. The composition according to claim 1 or 2, wherein the indigestible dextrin and casein hydrolyzate are contained in a mass ratio of 10: 0.001 to 1: 1.
4. The casein hydrolyzate contains a peptide composed of Met-Lys-Pro, and is in an amount of 5000 to 100,000 parts by weight of indigestible dextrin with respect to 1 part by weight of the peptide. The composition as described.
5. The composition according to any one of claims 1 to 4, which is used for preventing an initial symptom of stroke.
6. The composition according to any one of claims 1 to 5, which is a pharmaceutical composition or a food / beverage product composition.
7. The composition according to any one of claims 1 to 6, which is a fermented food or drink.
8. The composition according to any one of claims 1 to 7, comprising a unit packaging form.
9. A method for preventing stroke, in which casein hydrolyzate and indigestible dextrin are administered or ingested.
10. Casein hydrolyzate and indigestible dextrin used for the prevention of stroke.
11. Use of casein hydrolyzate and indigestible dextrin for the manufacture of a composition for preventing stroke.