JP2006265139A - New peptide - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a peptide having excellent ACE (angiotensin-converting enzyme) inhibitory activity. <P>SOLUTION: The soybean whey protein, one of microcomponents in soybean, is used as a substrate and hydrolyzed with a protease to obtain a peptide of Val-Lys-Pro having high ACE inhibitory activity. The present invention has been achieved based on this finding. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

  The present invention relates to a novel peptide, and particularly to a novel physiologically active peptide having an angiotensin converting enzyme (Angiotensin Converting Enzyme, hereinafter referred to as “ACE”) inhibitory activity.

  It has been noted that peptides obtained by hydrolyzing animal and vegetable proteins have various physiological activities, and in recent years, research on identifying amino acid sequences of peptides that express physiological activities has become active, and the sequences are also being revealed. However, since there are innumerable combinations of amino acid sequences, it is still meaningful to find new physiological activities in peptides having specific sequences.

Among the studies on the physiological activity of the above peptides, the most research has been done on blood pressure.
The number of patients with hypertension, which is a typical lifestyle-related disease, has been increasing year by year, and research has been conducted on its cause and effective countermeasures. In the onset of hypertension, a pressor enzyme system called a renin-angiotensin system (Non-patent Document 1) and a hypotensive enzyme system called a calicin / kinin system play important roles.

  According to this, in the enzyme system, ACE converts angiotensin I into angiotensin II, which is a potent pressor peptide, and inactivates bradykinin, which is a hypotensive peptide, and is deeply involved in increasing blood pressure.

  Therefore, inhibiting the activity of ACE has a close correlation with the action of suppressing an increase in blood pressure. Based on this recognition, various substances having ACE inhibitory activity have been searched and reported so far.

For example, gelatin collagenase digest [Patent Document 1], cattle casein trypsin digest [Patent Documents 2 to 4], zein (γ-zein) thermolysin digest [Patent Document 5], isolated soy protein thermolysin digestion ACE inhibitors and the like have been reported in products [Patent Literature 6], pepsin degradation products of sardine muscle [Patent Literature 7], or thermolysin degradation products of bonito [Patent Literature 8].
It is also known that soybean peptide obtained by enzymatic hydrolysis of soybean protein enhances ACE inhibitory activity [Patent Document 6]. This soy peptide is mainly composed of hydrolyzed 7S globulin (β-conglycinin) and 11S globulin (glycinin), which are the main proteins of soybean.

However, among the peptides whose amino acid sequences are specified, only those that have angiotensin converting enzyme inhibitory activity in in vitro tests are screened, and those that actually have a blood pressure lowering effect in animal tests and clinical tests are recognized. There are few reports, and there are many reports that the effect on humans has not been demonstrated. Even if such a peptide is used for a medicine or health food, the expected effect cannot be obtained.
In addition, when considering preparing a peptide having a highly active specific amino acid sequence at low cost, conventional food materials such as animal and vegetable proteins are expensive, and there are many problems in practical application.

(References)
Japanese Patent Laid-Open No. 52-148631 JP 57-15435 A Japanese Patent Publication No. 60-23086 Japanese Patent Publication No. 60-23087 JP-A-2-36127 JP-A-62-169732 Japanese Patent Laid-Open No. 3-11097 JP-A-4-144696 Itoh H, et al. J. Clin Invest, 91 2268 (1993)

  Therefore, the present invention provides a peptide having a novel sequence, provides a peptide having a high physiological activity, and particularly provides a peptide having an ACE inhibitory activity effective in treating, improving or preventing hypertension. Furthermore, an object of the present invention is to provide a low-cost and highly active ACE inhibitory peptide that can be prepared from inexpensive raw materials such as by-products normally discharged in food production.

  In view of the above problems, the present inventors obtained a substrate for obtaining a higher activity ACE inhibitor in a specific fraction of soybean, and obtained knowledge that the ACE inhibitory activity varies depending on the fraction. It was. As a result of further earnest research, hydrolyzate based on β-conglycinin and glycinin, which are the main storage proteins of soybean, by digesting with soybean whey protein, which is a trace protein in soybean, as a substrate. In addition to the above, it has been found that peptides having high ACE inhibitory activity can be obtained. Furthermore, the present inventors have found that the ACE inhibitory peptide present in the hydrolyzate is a tripeptide composed of Val-Lys-Pro, which is considered to be derived from soybean cystatin, and have completed the present invention.

That is, the present invention
(1) a novel peptide characterized by being represented by Val-Lys-Pro,
(2) The peptide according to 1 above, which has physiological activity,
(2) The peptide according to 2 above, wherein the physiological activity is an angiotensin converting enzyme inhibitory activity,
(3) The peptide according to the above item 1, obtained by hydrolyzing a protein derived from soybean whey with a protease,
(4) An antihypertensive agent comprising the peptide according to 1 above,
(5) A blood pressure lowering food containing the peptide according to 1 above,
(6) Use of the composition described in 1 above in the production of a blood pressure lowering agent or a food product for blood pressure lowering.

  The present invention can provide a novel peptide. Since this peptide has a high ACE inhibitory activity and has a physiological action to lower blood pressure, it can be provided as a blood pressure lowering agent or a food for lowering blood pressure. This peptide can be obtained inexpensively and efficiently by hydrolyzing soy whey or soy whey protein. In addition, since this peptide is derived from nature, it has high safety and can be used as a food without any problem. Furthermore, since various by-products of various soybean products can be effectively used in the present invention, it can be manufactured at a low cost, and it is very useful in terms of the environment.

The physiologically active peptide of the present invention is represented by the sequence “Val-Lys-Pro” and is a novel peptide not described in any literature. Val here means valine, Lys means lysine, Pro means proline, and all of these amino acids are L-forms.
One of the physiological activities of this peptide is ACE inhibitory activity.

  The bioactive peptide of the present invention is not particularly limited, but for example, a protein derived from a plant or animal such as soybean is hydrolyzed with a protease or synthesized by applying a conventional means for peptide synthesis. Can also be manufactured. These methods will be described. The former is preferable in that an inexpensive raw material can be used. In particular, a method of degrading proteins in soybean whey, which has not been useful as a waste solution in the production of separated soybean protein or concentrated soybean protein, with protease is preferable.

First, a method for hydrolyzing a protein with a protease will be described.
The soy whey preferably used in the present invention is a product obtained by removing most of the main storage proteins of soybeans and concentrating other trace proteins from defatted soybeans and soybeans during or after extraction with water. Specifically, there are by-products generated during the manufacture of various processed soybean products, that is, the supernatant after acid precipitation of the separated soy protein, the cleaning liquid of concentrated soy protein (acid concentrate, etc.), the waste liquid generated during the production of tofu and soy sauce, etc. included. The following is a general production example of soybean whey, but it is not particularly limited as long as it is a method in which most of soybean main storage proteins are removed and other trace proteins are concentrated.

(Isolated soy protein whey)
The defatted soybean flakes are extracted with water or dilute alkaline aqueous solution (about pH 8-9), the residue is removed by centrifugation, and the supernatant is recovered to obtain defatted soymilk. Hydrochloric acid is added to adjust the pH to around 4.5, and the mixture is separated into a whey fraction and an acid precipitation fraction by centrifugation. The obtained acid-precipitated fraction is dispersed in water, neutralized with an aqueous alkaline solution, and spray-dried to obtain a separated soy protein. On the other hand, a separated soy protein whey that is a whey fraction is obtained.

(Concentrated soy protein whey)
Water is added to the defatted soybean and washed with hydrochloric acid adjusted to about pH 4.5. The insoluble fraction is collected, neutralized, dried and ground, and concentrated soy protein (acid concentrate) is obtained by washing with diluted acid. Concentrated soy protein whey, which is a soluble fraction, is obtained as a by-product.

  Depending on the preparation method, the soybean whey usually contains about 15 to 30% by weight of crude protein per total solid content. Its composition is different from the main storage protein of soybean, and lectin in total protein is 10-20%, Kunitz-type trypsin inhibitor is 30-50%, and other minor proteins such as β-amylase, lipoxygenase, soybean cystatin are the main components. ing.

  As a raw material for obtaining the physiologically active peptide of the present invention, the above-described soybean whey may be used as it is, or soybean whey protein in which the protein is further concentrated may be used. Soy whey or soybean whey protein has more crude protein per total solid content, and it is appropriate to contain at least 15% by weight, more preferably 45% by weight or more, and even more preferably 75% by weight or more.

The method for obtaining the soy whey protein is not particularly limited, such as those obtained by further removing low-molecular sugars from soybean whey, further removing ash in them, or excluding most of the non-protein, The degree of purification can be changed according to the purpose.
For example, it is preferable to use a method of recovering heated aggregates denatured by heating as described below, or a method of concentrating proteins by exposing the heated aggregates to an acid, washing impurities, and so on.

  A preferred method for preparing soybean whey protein is shown below. For example, soybean whey is heated, and soybean whey protein that is heated and aggregated is recovered. The heating temperature is set to a temperature sufficient to denature soybean whey protein, preferably 80 to 120 ° C, more preferably 85 to 100 ° C. When the heating temperature is less than 80 ° C., the growth to aggregates is insufficient, and when the heating temperature exceeds 120 ° C., coloring due to browning or the like is likely to occur. The heating time may be a time sufficient for the formation of aggregates, and varies depending on the temperature, but it is sufficient to perform the heating in the range of 5 to 60 minutes. Moreover, when heating soy whey, alkaline earth metal ions such as calcium and magnesium coexist in an amount of 0.02 to 1% by weight based on the amount of soybean whey, precipitation of soybean whey protein is promoted. It is appropriate that the pH of soybean whey at the time of heating is 2 to 9, preferably 5 to 6. The obtained soybean whey protein contains about 45 to 55% by weight of crude protein and about 30% by weight of ash per total solid content.

  Furthermore, the solubilized ash and other impurities are removed by adding water to the heat-aggregated soybean whey protein and exposing to pH 4 or less, more preferably pH 3 or less using an acid such as hydrochloric acid. Next, after neutralizing to pH 6.5-9, preferably pH 7-8, and solubilizing by heating at 100-150 ° C., preferably 110-120 ° C., to obtain soybean whey protein of higher purity Can do. The obtained soybean whey protein contains 75 to 85% by weight of crude protein per total solid content, and the ash content is reduced to 10% by weight or less.

  Next, a protease is allowed to act on the soybean whey or soybean whey protein to prepare a hydrolyzate. Further, the hydrolyzate is fractionated by means of fractionation by molecular weight by means of gel filtration, membrane filtration or the like, or fractionation means utilizing adsorption characteristics such as adsorption resin or ion exchange resin. A fraction is obtained by fractionating the fraction.

  The molecular weight of the peptide contained in the hydrolyzate or a fraction thereof is suitably 100 to 2000, preferably 200 to 1000, and more preferably 200 to 500. In the peptide, the peptide showing ACE inhibitory activity is a tripeptide having an amino acid sequence of “Val-Lys-Pro” as a result of analysis by an amino acid sequencer, and the IC50 value of the ACE inhibition rate is 3 μM. The tripeptide is known to be derived from soybean cystatin because it exists in the primary sequence of soybean cystatin in soybean whey protein. Therefore, the higher the content of soybean cystatin, which is the main source of the ACE inhibitory peptide of the present invention, in soybean whey protein is preferable. Soya cystatin is a cystatin contained in soybean, and cystatin is a protein that specifically inhibits cysteine protease (Arai, Journal of Soy Protein Research Society, Vol. 16, 67-69, 1995. ).

  As a method of obtaining a hydrolyzate by causing protease to act on soybean whey or soybean whey protein, after making protease act, the pH is made acidic (preferably pH 4-5) and heated to remove insoluble fractions, A method for recovering the soluble fraction is preferred. Although it does not specifically limit as a protease to be used, In order to obtain higher ACE inhibitory activity, microorganism-derived, plant-derived or animal-derived endo-type proteases are preferable. Specifically, metal proteases (thermolysin etc.), serine proteases (trypsin) , Chymotrypsin, thrombin, plasmin, elastase, subtilisin, etc., thiol protease (papain, ficin, bromelain, cathepsin B, etc.), aspartic protease (pepsin, chymosin, cathepsin D, etc.), etc. can be used. Particularly preferred are thermolysin, subtilisin, papain and bromelain.

The hydrolyzed solution obtained by the above hydrolysis is a mixture containing the novel peptide of the present invention and other peptides, and can be used as it is for a pharmaceutical or food as a peptide-containing product containing the peptide of the present invention. If necessary, the peptide of the present invention can be purified or isolated at a high concentration.
In purifying the peptide of the present invention from the hydrolyzed solution, the hydrolyzed solution is used as it is or after the hydrolyzed solution is filtered by a known operation such as centrifugation, followed by extraction, concentration, drying and the like, Difference in adsorption affinity for various adsorbents, difference in solubility or solubility in various solvents, difference in partitioning between two immiscible liquid phases, difference in elution rate based on molecular size, The peptide of the present invention can be fractionated by appropriately selecting a fractionation means utilizing the difference in precipitation or precipitation rate. These purification means can be applied alone or in combination in any order as necessary, and can be applied in an inverted manner.
The average molecular weight of the obtained fraction is 200 to 1000, more preferably 200 to 500.

Next, a method for producing the peptide of the present invention by a peptide synthesis method will be described. The synthesis method is performed by a liquid phase method or a solid phase method, and any known means may be applied. For example, a raw material having a reactive carboxyl group corresponding to one of two kinds of fragments that are bisected at an arbitrary position of a peptide bond and a raw material having a reactive amino group corresponding to the other fragment are 2- (1H- Benzotriazole-1-yl) -1,1,3,3-tetramethyluronium hexafluorophosphate (HBTU) can be condensed by a method using an active ester or a method using carbodiimide.
Functional groups that should not participate in the reaction in this condensation are protected by protecting groups. Examples of the amino-protecting group include benzyloxycarbonyl (Bz) and t-butyloxycarbonyl (Boc). Examples of the protecting group for the carboxyl group include groups capable of forming alkyl esters, benzyl esters, etc. In the case of the solid phase method, the carboxyl group at the C-terminal is chlorotrityl resin, chloromethyl resin, oxymethyl resin, P-alkoxy. Bound to a carrier such as benzyl alcohol resin.
After completion of the condensation reaction, the protecting group is removed, but in the case of the solid phase method, the bond between the C-terminal of the peptide and the resin is further cleaved, and the product is purified according to the usual method. Examples of such purification include reverse phase liquid chromatography, ion exchange chromatography, affinity chromatography, and the like. Analysis of the synthesized peptide is performed by a method such as a protein sequencer or LC-MS that reads an amino acid sequence from the C-terminal by Edman degradation.

Using the peptide of the present invention or a content thereof as a basic raw material, if necessary, using other known pharmaceutically acceptable raw materials, it can be formulated into various dosage forms by a known production method into a medicine. . The use of the medicine is not particularly limited, but can be a blood pressure lowering agent having an ACE inhibitory action. This blood pressure lowering agent is effective for lowering blood pressure when administered to a hypertensive human.
Examples of other raw materials used here include various materials commonly used in ordinary drugs, such as diluents or excipients such as fillers, binders, disintegrants, surfactants, lubricants, and the like.
The mode of administration is not particularly limited and can be appropriately selected depending on the therapeutic purpose. For example, in the case of oral administration, tablets, pills, powders, solutions, suspensions, emulsions, granules, hard capsules, soft capsules It can be administered in the form of a capsule or the like, or in the case of parenteral administration, in the form of an injection, a suppository or the like. Oral administration is desirable from the viewpoint of simplicity.

Various foods containing the peptide of the present invention can be produced by a known production method using the peptide of the present invention or a content thereof as a basic raw material and using other known raw materials as necessary. The physiological function expressed by the intake of this food is not particularly limited, but is particularly effective for humans with hypertension and those who tend to have high blood pressure, and is effective for the prevention and improvement of hypertension.
The food is not particularly limited. For example, oil-in-water emulsified foods such as cream; water-in-oil emulsified foods such as margarine; edible oils; beverages such as soft drinks, tea-based drinks, and milk drinks; milk, cheese, yogurt, etc. Dairy products; Soy milk, fermented soy milk, soy protein beverages, tofu, natto, deep-fried, deep-fried, deep-fried soy products such as hamburgers; processed meat products such as hamburger, meatballs, deep-fried chicken, nuggets, etc .; And confectionery such as chocolate, cake, frozen dessert, cereal, rice cake, gum, and tablet; bread such as bread, confectionery bread, and donut; and cooked rice such as rice, sushi, and rice cake.
Since the content of the peptide of the present invention can be easily measured in food, it can be used as an active ingredient (involved ingredient) in the main body of food or food packaging, containers, labels, advertisements, pamphlets, etc., for example, “angiotensin converting enzyme Since it has an inhibitory action, it lowers blood pressure and is suitable for the prevention and improvement of hypertension "and other physiological functions," Val-Lys-Pro is included as an active ingredient "," Val-Lys- It can be a food for health use such as a food for specified health, which directly displays “effective intake of Pro” and the like. Of course, even if such a direct indication is not made, an indirect indication that makes it possible to imagine that taking food containing Val-Lys-Pro is effective in preventing and improving diseases such as hypertension is effective. Foods for health uses that are equivalent to the above are also encompassed by the present invention.

  The intake of the peptide of the present invention can be appropriately selected depending on the usage, age of the subject, sex, other conditions, degree of disease, purpose, etc., and is not particularly limited. Usually, the amount is in the range of about 0.1 mg to 2 g, preferably about 1 mg to 1 g per day. The intake amount as an agent or food may be set in relation to the peptide content so as to satisfy the above-described peptide intake range. However, many of the pharmaceuticals may cause safety problems if taken in excess of the appropriate amount, whereas this peptide is obtained by fractionating and purifying soy whey, so there is almost no worry about side effects. It does not prevent the setting of the range exceeding the upper and lower limits. It can also be taken in two to four times a day.

  The content of the peptide of the present invention in the agent or food is preferably 0.01 to 100% by weight. More preferably 0.5 to 80% by weight is appropriate.

  EXAMPLES Examples of the present invention will be described below, but the present invention is not limited to these examples, and it goes without saying that various modifications can be made without departing from the gist of the present invention.

◎ Production Example 1 (Preparation of soy whey protein hydrolyzate)
Ten times of water (20 L) was added to 2 kg of defatted soybeans, pH was adjusted to 4.3 with hydrochloric acid while stirring, and the mixture was centrifuged to remove insoluble matters, and 16 L of supernatant was collected.
Next, slaked lime was added to adjust the pH to 5.3, and the protein content insoluble and aggregated by heating to 95 ° C. was recovered by centrifugation. 2 L of water was added to the resulting precipitate, hydrochloric acid was added to adjust the pH to 2.0, and acid-soluble components were removed by centrifugation (1000 g × 5 minutes). Further, 0.2 L of water was added to the precipitate, and the pH was adjusted to 8.5 with sodium hydroxide, followed by heating at 120 ° C. for 10 minutes to solubilize the protein to obtain soybean whey protein. The crude protein content in the total solid content of the protein was 81% by weight. According to electrophoresis, soy globulin (glycinin and β-conglycinin), which is the main storage protein of soybean, was hardly present, and soy lectin and Kunitz-type trypsin inhibitor were mainly present. Soy cystatin was also present.

Add 8% endo-type protease "Protease S" (manufactured by Amano Enzyme) with a crude protein content of 8% to the crude purified whey protein, and adjust the pH to 8 (or 7.5 or higher)
The reaction was carried out at 70 ° C. for 4 hours while maintaining at 8.5 or lower). The reaction solution was heated at 100 ° C. for 5 minutes to stop the reaction, centrifuged (18,000 g, 10 minutes), and the supernatant was recovered to obtain soybean whey protein hydrolyzate.

This was subjected to gel filtration (gel filtration conditions: Sephadex G-25 (bed: 2.6X96 cm), flow rate: 30 ml / h, mobile phase: deionized water, detection: 280 nm), and a molecular weight fraction with a molecular weight of 200 to 1000 was obtained. Collected and reversed-phase HPLC (reverse-phase HPLC conditions: Wakosil-II 5C18AR (4.6X250mm), CAPCELL PAK C18AQ (
4.6X250mm), YMC-Pack C4 (4.6x250mm), flow rate 1ml / min, mobile phase: milli-Q water containing 0.1% trifluoroacetic acid (TFA) and acetonitrile containing 0.1% TFA, detection: 216nm) A high peak was detected and collected. Furthermore, as a result of examining the peptide sequence with an amino acid sequencer, it was found to be Val-Lys-Pro.

◎ Production Example 2 (Production of synthetic peptide Val-Lys-Pro)
Based on the result obtained in Production Example 1, a synthetic peptide Val-Lys-Pro was produced.
0.6 g of commercially available Fmoc-Pro (tBu) resin (substitution rate 0.5 meq / g) is dispensed into a reaction vessel of a PS3 type peptide synthesizer (Protein Technologies), and a new peptide is synthesized as follows. It was. First, the above resin is put in a reaction vessel, and 1 mmol of Fmoc-Lys and 1 mmol of HBTU as an activator dissolved in 10 ml of dimethylformamide containing 0.4 M N-methylmorpholine are added to the reaction vessel. The reaction was stirred at room temperature for 20 minutes.

  Fmoc-Val was coupled from the C-terminal in the same manner as in the above-mentioned method in which Fmoc group was removed in 20 ml of dimethylformamide containing 20% by volume of piperidine, and then Fmoc-Lys was coupled, Val-Lys-Pro (tBu) resin was obtained. The resin was mixed in 10 ml of deprotection solution (mixture of 90% by volume trifluoroacetic acid, 5% by volume thioanisole, 3% by volume ethanedithiol, 2% by volume ethyl methyl sulfide, 1% by volume methyl indole) at room temperature. Stir for hours to release the peptide from the resin.

  40 ml of cold ether was added thereto to precipitate the peptide, and further washed with cold ether three times to obtain a crude peptide. This was developed and purified by reverse phase chromatography on an ODS column (Cosmosil5C18-ARII, 20 × 250mm) with a linear concentration gradient of acetonitrile containing 0.1% by weight trifluoroacetic acid, and the sequence of Val-Lys-Pro was determined. Peptide having was obtained. This product was analyzed by a protein sequencer (“type 492” manufactured by Applied Biosystems) and confirmed to have the above sequence.

Example 1 (Measurement of angiotensin converting enzyme inhibitory activity)
The synthetic peptide Val-Lys-Pro produced in Production Example 2 was measured for ACE inhibitory activity according to a known measurement method (Cushman-cheung method).
Rabbit-derived ACE (manufactured by Sigma) was dissolved in 125 mM borate buffer (pH 8.3) to prepare 0.1 Unit / ml. On the other hand, as a substrate, Bz-Gly-His-Leu (manufactured by Sigma) was dissolved in 125 mM borate buffer (pH 8.3) containing NaCl so as to be 4.2 mM. Moreover, the sample which measures inhibitory activity measured the density | concentration of the proteolysate by the Raleigh method, and prepared the thing with a known density | concentration. 150 μl of substrate solution, 50 μl of sample solution, and 50 μl of ACE solution were mixed and reacted at 37 ° C. for 30 minutes. The final concentration in the reaction solution is 3.5 mM substrate and 400 mM NaCl. Next, 250 μl of 1N hydrochloric acid was added to stop the reaction, 1.5 ml of ethyl acetate was added, and the mixture was stirred for 15 seconds, further centrifuged at 3000 G × 2 minutes, and 1 ml of the ethyl acetate layer was collected. The mixture was heated to 140 ° C. for 10 minutes with a block heater while blowing nitrogen gas, evaporated to dryness, 1 ml of distilled water was added thereto, and the absorption of extracted hippuric acid (absorbance at 228 nm) was measured. The angiotensin converting enzyme inhibition rate was determined by the following equation [1]. However, ODs is the absorbance when the sample is added and measured as described above, ODsb is the absorbance when 250 μl of 1N hydrochloric acid is added and measured before reacting the above mixed solution, and ODc is the above mixture. Absorbance when measured without adding a sample to the solution, ODcb is the absorbance when 250 μl of 1N hydrochloric acid was added and measured before reacting without adding the sample to the above mixed solution.

(Equation 1)
ODs−ODsb
(1- ──────) × 100 [1]
ODc−ODcb

  Then, from the obtained inhibition rate, in order to confirm the inhibition activity of each sample, a concentration (IC50) at which the ACE inhibition rate of the degradation product was 50% was obtained. The obtained results are shown in Table 1.

(Table 1) ACE inhibitory activity of each protein hydrolyzate ───────────────────────────
Peptide ACE inhibitory activity (IC50)
────────────────────────────
Example 1 Val-Lys-Pro 3 μmol / L
────────────────────────────

  From the experimental results, the IC50 concentration was low and showed high ACE inhibitory activity.

Example 2 (single administration test of synthetic peptide Val-Lys-Pro to spontaneously hypertensive rats)
Using 10 spontaneously hypertensive rats (SHR / Izm, Japan SLC), 5 were distilled water, 5 were Val-Lys-Pro peptide at a rate of 100 mg / kg, and a single dose was administered with a gastric sonde. did. Blood pressure was measured by the tail-cuff method using an unheated non-invasive sphygmomanometer model MK-2000 (Muromachi Kikai) before administration and every 2 hours until 8 hours after administration. As a result, a statistically significant difference was observed after 4 hours and 8 hours, and the blood pressure decreased (FIG. 1).

Effect of Val-Lys-Pro administration on blood pressure of SHR rats (19 weeks old) of Example 1

Claims (10)

A novel peptide characterized by being represented by Val-Lys-Pro. The peptide according to claim 1, which has physiological activity. The peptide according to claim 2, wherein the physiological activity is an angiotensin converting enzyme inhibitory activity. The peptide according to claim 1, which is obtained by hydrolyzing a protein derived from soybean whey with a protease. The peptide according to claim 1, which is derived from soybean cystatin. The pharmaceutical containing the peptide of Claim 1, or its content. The medicament according to claim 5, which is an antihypertensive agent. A food containing the peptide according to claim 1 or a content thereof. The food according to claim 7, which is used for lowering blood pressure. Use of the novel peptide according to claim 1 in medicine or food production.

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