WO2005063245A1 - Composition destinee a baisser la tension arterielle - Google Patents

Composition destinee a baisser la tension arterielle Download PDF

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Publication number
WO2005063245A1
WO2005063245A1 PCT/JP2004/019397 JP2004019397W WO2005063245A1 WO 2005063245 A1 WO2005063245 A1 WO 2005063245A1 JP 2004019397 W JP2004019397 W JP 2004019397W WO 2005063245 A1 WO2005063245 A1 WO 2005063245A1
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Prior art keywords
blood pressure
composition
sample
protease
bonito
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PCT/JP2004/019397
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English (en)
Japanese (ja)
Inventor
Hitoshi Hariu
Masaaki Tokitaka
Masanori Asukai
Hiromi Imamoto
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Shimaya Co., Ltd.
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Priority to JP2005516656A priority Critical patent/JPWO2005063245A1/ja
Publication of WO2005063245A1 publication Critical patent/WO2005063245A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4164—1,3-Diazoles
    • A61K31/4172—Imidazole-alkanecarboxylic acids, e.g. histidine
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/17—Amino acids, peptides or proteins
    • A23L33/175—Amino acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
    • A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/472—Non-condensed isoquinolines, e.g. papaverine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/12—Antihypertensives
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs

Definitions

  • the present invention relates to a composition for lowering blood pressure comprising, as an active ingredient, at least one of histidine, leucine, isoleucine, glutamic acid, serine or phenylalanine or a salt thereof, or a substance derived from a natural product as an active ingredient. Things.
  • Oligopeptides such as peptides having a Pro-Ala-Gln-Lys skeleton (Patent Document 5) have been reported to exhibit a blood pressure lowering effect based on angiotensin converting enzyme (ACE) inhibitory activity.
  • ACE angiotensin converting enzyme
  • Non-patent Document 1 and 2 a peptide having 2 to 9 amino acids, which is contained in a thermolysin hydrolyzate of dried bonito, has an ACE inhibitory action and exhibits a blood pressure lowering action.
  • VaKTyr contained in sardine peptides obtained by treating sardine surimi with pepsin or alkaline protease has ACE inhibitory activity, and in fact, blood pressure was measured in experiments using spontaneously hypertensive rats (KSHR). It is reported to have a descending effect (Non-Patent Document 3).
  • Non-Patent Document 4 arginine, one of the amino acids, has a blood pressure lowering effect in systole and diastole (Non-Patent Document 4), but arginine exhibits a blood pressure lowering effect.
  • the increase in heart rate is also shown.
  • Non-Patent Documents 5 and 6 It has also been reported that tyrosine or L-tributophan exhibits a blood pressure lowering effect when administered intraperitoneally to rats.
  • histidine, leucine, isoleucine, glutamic acid, serine, or phenylalanine or a salt thereof, or a content thereof has a hypotensive effect upon oral ingestion.
  • Patent Document 1 Patent No. 3193085
  • Patent Document 2 Japanese Patent No. 3110075
  • Patent Document 3 Patent No. 3093378
  • Patent Document 4 Patent No. 3012291
  • Patent Document 5 Patent No. 2922247
  • Non-Patent Document 1 Food and Development 1992, Vol. 27, No. 12, pp. 43-45
  • Non-patent Literature 2 Clinical and Experimental Pnarmacology and Physiology, (1995),
  • Non-Patent Document 3 Journal of the Japanese Society of Nutrition and Dietary Ethics, 2000, Vol. 53, No. 2, pp. 77-75 Special Publication 4: K. hishikaw et al., “Role of L—arginine— nitric oxide pathway in hyper tension ", J. Hypertension 11, 639, 1993
  • Non-Patent Document 5 Alan F. Sved et al., Proc. Natl. Acad. Sci. USA, Vol. 76, No. 7, pp3511-3514, July 1979.
  • Non-Patent Document 6 Alan F. Sved et al., J. Pharmacol.Exp.Ther.221: 329-333, 1982 Disclosure of the invention
  • the present invention relates to amino acid contained in an aqueous solvent extraction residue of bonito dried in the process of producing dried bonito as a fish meat dried product, which has been widely used as a food since ancient times, and further in the process of producing bonito dried seasoning. It is an object of the present invention to make a new use.
  • the inventors of the present invention have conducted intensive studies in the process of developing a new use of the bonito component, with the aim of developing a new use of the amino acid contained in the bonito, particularly the extract and residue of the bonito. It was found that leucine, isoleucine, glutamic acid, serine, and phenylalanine, their salts, and their contents derived from natural products have a hypotensive effect.
  • the present invention it is intended that at least one of histidine, leucine, isoleucine, glutamic acid, serine or phenylalanine or a salt thereof, or a substance derived from a natural product is contained as an active ingredient.
  • the present invention provides a thread and composition for lowering blood pressure and a food containing the composition.
  • the composition for lowering blood pressure mainly comprises histidine, leucine, isoleucine, glutamic acid, serine or phenylalanine, which is one of the amino acids, or a salt thereof, or a substance derived from a natural product. As it is a component, it can be used safely.
  • the aqueous solvent extraction residue of bonito dried in large quantities in the process of producing bonito flavored seasonings can be effectively used as the amino acid content.
  • composition for lowering blood pressure of the present invention comprises at least one of histidine, leucine, isoleucine, glutamic acid, serine or phenylalanine (hereinafter abbreviated as amino acid in the present invention) or a salt thereof, or Contains these natural ingredients as active ingredients
  • the amino acid as an active ingredient may be obtained by a synthesis or fermentation method, or may be derived from natural sources.
  • dried fish meat products For example, bonito may be extracted with an aqueous solvent, and the residue may be decomposed with a proteolytic enzyme.
  • the method using the aqueous solvent extraction residue is particularly preferable because the extraction residue can be effectively used.
  • the extraction method is not particularly limited, but is usually performed using an extraction solvent in an amount of about 50 to 50 times (volume), preferably about 2 to 20 times the amount of the extraction material.
  • the extraction temperature can be arbitrarily set between room temperature and the boiling point of the extraction solvent. For example, it is preferable to perform the extraction at a temperature between room temperature and the boiling point of the extraction solvent while shaking or refluxing. Alternatively, a mixture consisting of an extraction material and an extraction solvent may be boiled.
  • the extraction time is appropriately 5 minutes and several hours, preferably about 20 minutes and 12 hours. Such an extraction operation may be performed only once or may be repeatedly performed a plurality of times.
  • Examples of the extraction solvent include aqueous solvents, that is, aqueous alcohols such as water or aqueous ethanol.
  • the proteolytic enzyme degradation product of the low-molecular-weight fraction or high-molecular-weight fraction of the extracted extract by a conventional method such as ultrafiltration is used. You can use it.
  • the above-mentioned bonito can be used as it is, and it is preferable in terms of extraction efficiency to use the crushed mash and the dried bonito.
  • the separated extraction residue can be subjected to a digestion treatment with a protease.
  • the residue discharged in a large amount in the process of producing the bonito flavored seasoning can be used as it is or after drying.
  • the proteolytic enzyme used to obtain an amino acid or its content from the residue is, for example, a normal proteolytic enzyme such as pepsin, trypsin or chymotrypsin, or derived from Bacillus stearothermophilus.
  • a normal proteolytic enzyme such as pepsin, trypsin or chymotrypsin, or derived from Bacillus stearothermophilus.
  • the protection Pasease S protease derived from ⁇ -silium citrinum, peptidase R derived from Rhizopus oryzae, or anorecalypeptidase.
  • the method for obtaining the amino acid by decomposing the aqueous solvent extraction residue with a protease is not particularly limited.
  • the aqueous solvent extraction residue of bonito is used.
  • Add 4 times the amount of water to the mixture, homogenize it sufficiently, add hydrochloric acid to adjust it to a strong acidity, for example, around ⁇ .6, add 1/100 of the total weight of pepsin, and add 5% at 37 ° C for 5 hours Can be subjected to enzymatic degradation with slow stirring.
  • the mixture is boiled at 100 ° C. for 10 minutes to inactivate the enzyme to terminate the reaction, and a filtrate rich in amino acids can be obtained by suction filtration. If necessary, for example, sodium hydroxide can be added to the filtrate thus obtained to form a salt thereof.
  • Each amino acid or a salt thereof can be isolated from the above-mentioned amino acid-rich filtrate according to a known technique.
  • the salt of an amino acid in the present invention means a pharmaceutically acceptable salt.
  • an addition salt with an acid such as a hydrochloride, or a salt with an alkali metal atom such as a sodium salt or a potassium salt can be mentioned.
  • pepsin is used except that the pH is adjusted to the optimum pH of each protease and the enzyme reaction is performed. It can be performed according to the case.
  • an amino acid-rich solution can be obtained efficiently by performing the same procedure as in the case of pepsin except that the enzyme reaction is carried out by simultaneously adding trypsin or chymotrypsin or both enzymes.
  • the above amino acid-rich solution may be used as it is or after being concentrated. Further, the above-mentioned concentrated liquid may be freeze-dried or spray-dried and then solid-dried to be used as a composition.
  • Typical examples of the dried fish meat product in the present invention include, in addition to the dried bonito, dried products obtained by processing fish meat such as soda bonito, tobio, sardine, tuna, and mackerel.
  • Naturally occurring amino acids derived from natural products or their contents are not limited to those described above, and any amino acid containing the amino acid can be used as an active ingredient of the present invention.
  • soybean and mung bean having a particularly high content of the amino acid can be used as an active ingredient of the present invention, and can also be used as a raw material for obtaining the content of the amino acid or a salt thereof.
  • the amino acid-containing substance derived from a natural product that can be used as an active ingredient of the composition for blood pressure effect in the present invention is treated with a protease.
  • aqueous solvent extract obtained when producing a dried fish meat product, an extract of a dried fish meat product, or a digestion product of these with a proteolytic enzyme there may be mentioned an aqueous solvent extract obtained when producing a dried fish meat product, an extract of a dried fish meat product, or a digestion product of these with a proteolytic enzyme.
  • aqueous solvent extract obtained when producing the dry product is used as an active ingredient, it is preferable to use a filtrate obtained by filtering the extract and concentrating the filtrate.
  • the aqueous solvent extract of the dried fish meat product may be used as it is, or may be used after being concentrated.
  • the above-mentioned concentrated liquid may be freeze-dried or spray-dried and then solid-dried to be used as the composition.
  • ACE inhibitory activity is weak! Histidine (inhibition at 0.9 mg / ml is 50%), leucine (inhibition at 16 mg / ml or more is 50%), isoleucine (inhibition is 29 mg / ml) 50%), glutamic acid (50% inhibition at ⁇ 5.0 mg / ml), serine (50% inhibition at 16.4 mg / ml) or hue-alanine (50% inhibition at ⁇ 20 mg / ml) (KSHR) in an oral administration experiment with SHR rats without affecting the heart rate was found to significantly reduce blood pressure during systole and diastole.
  • At least one of histidine, leucine, isoleucine, glutamic acid, serine or feralanine, or a salt thereof is provided to a patient with hypertension or a person who is susceptible to hypertension.
  • a method for treating or preventing hypertension which comprises administering an effective amount for treating or preventing a blood pressure lowering composition containing these natural substances as an active ingredient.
  • composition for lowering blood pressure is prepared by adding an appropriate excipient or diluent to the above-mentioned amino acid or a substance derived from a natural product containing the same, and using the usual amino acid used in the field of pharmaceuticals. It can be formulated into a preparation by a known method and used.
  • preparations include solid preparations such as powders, fine granules, granules, tablets and capsules, and liquid preparations such as suspensions, solutions and syrups.
  • the excipients or additives include lactose, sucrose, starch, talc, cellulose, dextrin, sorbitol, calcium phosphate and the like.
  • binders e.g., syrup, gum arabia, gelatin, sorbitol, tragacanth or polyvinylpyrrolidone
  • lubricants e.g., magnesium stearate, talc or polyethylene glycol
  • disintegrants e.g., potato starch
  • humectants e.g., lauryl
  • tablets or capsules they can be formulated in a known manner, for example, as a sugar-coated tablet, for immediate release of the usual active ingredients. Further, as a sustained-release preparation for delaying or sustained release of the active ingredient, it may be coated with a polymer according to a method known to those skilled in the art.
  • water is usually used as a diluent.
  • Other additives may include sweeteners (e.g., sucrose or sorbitol), preservatives (e.g., methyl P-hydroxybenzoate, propyl p-hydroxybenzoate, or sorbic acid), coloring agents or flavors. Good.
  • Liquid preparations may be, for example, aqueous suspensions, solutions or syrups, or lyophilized products which are dissolved in water at room temperature before use or warmed before use.
  • the food containing the composition for lowering blood pressure of the present invention is mainly used as a health food for preventing hypertension.
  • the type is not particularly limited.
  • the food include ordinary foods such as sweets such as ukan, yogurt, and bun, soft drinks, teas, nutritional drinks, soups, breads and udon, and other health foods.
  • Healthy foods are foods that are more aggressive than normal foods and are intended to promote health, maintain health, and promote health.For example, liquid or semi-solid or solid products, specifically powders, Examples include granules, tablets, capsules and the like.
  • An ordinary food containing the composition for lowering blood pressure of the present invention is prepared by mixing or applying the composition of the present invention to the final food product or by adding, spraying, or the like. Can be manufactured.
  • the amount of the composition for lowering blood pressure of the present invention used as a medicament may be appropriately increased or decreased depending on the weight or symptoms of the patient, and the daily dose to an adult is, for example, histidine, leucine, isoleucine, glutamic acid, serine or About 0.1 to 10 g of feniralanine respectively.
  • composition for lowering blood pressure of the present invention when used in foods, histidine, leucine, iso-mouth, etc. are used in an amount that does not adversely affect the taste or appearance of the foods, for example, 1 kg of the target foods. It is appropriate to use it in the range of about 1.5 to 100 g as isine, glutamic acid, serine, or phenylalanine.
  • the amount of the amino acid can be appropriately increased or decreased without being limited to the above-mentioned amount of the amino acid.
  • composition of the present invention when used for cooking food, it is used in the form of a stick or pouch-shaped package containing a single use amount, or in the form of granules contained in a sprinkle container. Is appropriate.
  • compositions for lowering blood pressure of the present invention and their effects will be specifically described with reference to Examples, Production Examples and Test Examples, but the present invention is limited by these Examples and Production Examples. Not something.
  • Filter paper Advantech, type 5C
  • Microfilter Millex-LH (trademark)
  • Pepsin Sigma, from swine gastric mucosa
  • Chymotrypsin Sigma, from bovine spleen
  • Protease S Amano Enzym, from Bacillus stearothermophilus
  • Protease B from Amano Enzym, Penicillium citrinum
  • ⁇ Peptidase R Amano Enzym, derived from Rhizopus oryzae
  • Histidine Wako Pure Chemical Industries, Ltd., special grade
  • Water for oral administration Water for injection (Otsuka distilled water, manufactured by Otsuka Pharmaceutical Factory, lot number: 2G90P)
  • HPLC column Pharmacia, Superdex peptide 10 / 300GL
  • the above extraction residue was dried in a hot air drier at 70 ° C for 2 hours, allowed to cool, finely pulverized, and passed through a 60-mesh sieve to obtain a sample (1).
  • the above sample 1 (16.8 g, protein: 89.31%) was suspended in 168 ml of pure water. This suspension was adjusted to pH 2.0 with 20% HC1, 339 mg of pepsin was added, and the mixture was stirred at 37 ° C. for 12 hours. Subsequently, the pH was adjusted to 7.8 with a 20% NaOH solution, 169.5 mg of each of trypsin and chymotrypsin was added, and the mixture was stirred at 37 ° C for 12 hours. After completion of the reaction, the enzyme was inactivated by heating at 90 ° C. for 15 minutes, allowed to cool to room temperature, suction-filtered, and the filtrate was further filtered with a microfilter. The filtrate was freeze-dried to obtain a sample (2) (10 g).
  • Sample (5) (7.5 g) was obtained in exactly the same manner as for sample 4 above, except that the enzyme reaction was carried out at 45 ° C. using protease B.
  • Samples (6) and (8 g) were obtained in exactly the same manner as in Sample 4 above, except that the enzyme reaction was carried out at 45 ° C. using Peptidase R.
  • Roasted Aramoto Yushi (Roasted Katsuo Aramoto Yushi) is crushed to 2-3 mm or less, dried in hot air at 70 ° C for 2 hours, allowed to cool, finely pulverized, and passed through a 60 mesh sieve. (8) was obtained.
  • crushed mackerel product (Maruhachi Muramatsusha, crushed mackerel product HF) was extracted in 1.5 L of hot water (97 ° C or more) for 30 minutes, and the extracted mixture was filtered with a filter cloth. The extraction residue was dried in a hot air dryer at 70 ° C for 2 hours, allowed to cool, finely pulverized, and sieved through a 60 mesh sieve to obtain a sample (10).
  • the above dried bonito extract was dissolved in 10 ml of 30% aqueous acetonitrile per 1 g of extract and subjected to HPLC using 30% aqueous acetonitrile containing 0.1% trifluoroacetic acid as a mobile phase to obtain a fraction and a molecular weight of 2,000 or more. It was fractionated into fractions of 1500 or less and freeze-dried to obtain Sample (13) and Sample (14).
  • Table 1 Composition of free amino acids in bonito extract and raw bonito extract
  • 9-week-old male rats were subjected to a temperature of 22 ⁇ 3 ° C, a humidity of 50 ⁇ 20%, 12 hours of light (8: 00—20: 00)
  • the animals were preliminarily reared for 1 week in an environment with a ventilation rate of 13 to 17 times / hour.
  • the blood pressure and heart rate of SHR rats before and after administration of each sample were measured using a small animal non-warmed non-invasive sphygmomanometer (MK-2000, manufactured by Muromachi Kikai Co., Ltd.).
  • 10-week-old SHR rats are divided into groups of 5 so that systolic blood pressure is almost the same.
  • a predetermined amount of each sample obtained in the above example was dissolved in an aqueous solution for injection at the time of use, and orally administered at a rate of 4 ml / kg to 5 overnight fasted SHR rats per sample, The systolic and diastolic blood pressure and heart rate were measured 24 hours after administration.
  • the control group was orally administered distilled water for injection at a rate of 4 ml / kg.
  • the average value and standard error of each group were calculated for the values obtained in the sample administration test.
  • the significant difference between the groups was determined by testing the homogeneity of variance by the Bartlett method (5% significance level). The average values were compared according to the method). The significance levels were 5% and 1%.
  • Sample (1) was 500 mg / kg and 100 mg / kg, sample (3) per rat body weight Were administered to rats at 1000 mg / kg and 200 mg / kg, samples (9) and (10) at 500 mg / kg, and histidine at 100 mg / kg, respectively. After 24 hours Changes in systolic and diastolic blood pressure were measured. Table 4 shows the measurement results of systolic blood pressure and Table 5 shows the measurement results of diastolic blood pressure.
  • Sample (7) was administered to rats at 100 mg / kg per rat body weight as described above, and changes in systolic and diastolic blood pressure 4 hours after administration were measured. Table 7 shows the measurement results of systolic and diastolic blood pressure.
  • Samples (2), (5) and (9) were 100 mg / kg, sample (3) was 100 mg / kg and 500 mg / kg, and samples (8), (11) and (12) ) was administered to rats at 500 mg / kg and histidine at 50 mg / kg and 10 mg / kg, respectively, as described above, and changes in systolic and diastolic blood pressure 24 hours after administration were measured. It was measured.
  • Table 7 shows the measurement results of systolic blood pressure
  • Table 8 shows the measurement results of diastolic blood pressure. [0067] Table 7: Blood pressure lowering effects of samples (2), (3), (5), (8), (9), (11), (12) and histidine in rat systolic phase
  • Table 8 Blood pressure lowering effect of samples (2), (3), (5), (8), (9), (11), (12) and histidine in diastolic phase of rats
  • Control distilled water for injection
  • BSA control, bovine serum albumin
  • 10-week-old male rats were subjected to a temperature of 22 ⁇ 3 ° C, a humidity of 50 ⁇ 20%, 12 hours of light (8: 00-20: 00) and a ventilation rate of 13-17 times / hour for 1 week. Preliminarily reared.
  • the blood pressure and heart rate of SHR rats before and after administration of each sample were measured using a small animal non-warmed non-invasive sphygmomanometer (MK-2000, manufactured by Muromachi Kikai Co., Ltd.).
  • the numerical values obtained in the sample administration test are values obtained by calculating the average value and the standard error in each group.
  • the significant difference between the groups was determined by the test of equal variance by the Bartlett method (significance level 5%), and because of equal variance, one-way analysis of variance was performed.
  • the average values were compared according to the method).
  • the significance levels were 5% and 1%.
  • Samples (16)-(30) were applied to 5 rats per sample at the ratios shown in Tables 9 and 10, and the change in blood pressure during systole and diastole 12 hours after administration was measured.
  • Table 9 shows the measurement results of systolic blood pressure
  • Table 10 shows the measurement results of diastolic blood pressure.
  • Control distilled water for injection
  • Each number represents the standard error of the instep average.
  • a stick-shaped package containing 0.7 g per sample of the sample (13) obtained in the preparation of the sample (13) and the sample (14) in Example 1 was produced.
  • Example 5 1 part by weight of the sample (13) obtained in the preparation of the sample (13) and the sample (14) in Example 1 was mixed with 1 part by weight of lactose, and a stick-shaped bag containing 2 g of the sample (13) per packet Manufactured packaging Example 5
  • a stick-shaped package containing 0.7 g per sample of the sample (14) obtained in the preparation of the sample (13) and the sample (14) in Example 1 was produced.
  • a stick-shaped package containing 1 g of the sample (30) obtained in Production Example 1 per packet was produced.
  • One part by weight of the sample (30) obtained in Production Example 1 was mixed with 1 part by weight of ratatose to produce a stick-shaped package containing 4 g of the sample (30) per packet.
  • Histidine, leucine, isoleucine, glutamic acid, serine, and phenylalanine were each mixed one part at a time to obtain a mixture of amino acids.
  • a stick-shaped package containing 0.7 g of the mixture obtained in Example 9 per packet was produced.
  • Example 13 50 parts by weight of rice flour, 5 parts by weight of sugar, 10 parts by weight of whole egg, and 1 part by weight of the sample (30) obtained in Production Example 1 were weighed.
  • the rice flour that had been passed through a sieve was added in advance and mixed gently to form a dough, which was formed into an appropriate shape and baked in an oven to make a rice cracker.
  • Example 9 50 parts by weight of rice flour, 5 parts by weight of sugar, 10 parts by weight of whole egg, and 0.5 part by weight of the amino acid mixture of Example 9 were weighed.
  • the rice flour that had been passed through a sieve was added in advance and mixed gently to form a dough, which was formed into an appropriate shape and baked in an oven to make a rice cracker.
  • a rice cracker was prepared in the same manner as in Example 14, except that the amount of the amino acid mixture of Example 9 was changed to 0.5 part by weight and 2 parts by weight were used.
  • a cracker was prepared in the same manner as in Example 14, except that the amount of the amino acid mixture of Example 9 was changed to 0.5 part by weight and 5 parts by weight was used.
  • Example 17 in place of the sample (30) of Production Example 1 and 40 parts by weight of water instead of 5 parts by weight of the dried bonito extract and 45 parts by weight of water obtained in Example 2, • La 7 pieces.
  • Example 9 10 parts by weight of the amino acid mixture obtained in Example 9 was mixed with 15 parts by weight of ratatose and filled into a gelatin capsule to obtain a gelatin capsule containing 1 g of the amino acid mixture in one capsule.
  • At least one of amino acids or salts thereof, or a substance thereof can be used as an active ingredient of a safe composition for lowering blood pressure in medicine or food.

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Abstract

L'invention concerne une composition destinée à baisser la tension artérielle, qui se caractérise en ce qu'elle contient, comme principe actif, au moins un élément sélectionné dans le groupe constitué par histidine, leucine, isoleucine, acide glutamique, sérine, phénylalanine et leurs sels; ou une matière d'origine naturelle contenant ledit élément.
PCT/JP2004/019397 2003-12-26 2004-12-24 Composition destinee a baisser la tension arterielle WO2005063245A1 (fr)

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JP2005206528A (ja) * 2004-01-23 2005-08-04 Calpis Co Ltd アンジオテンシン変換酵素阻害剤及び該阻害剤を含む食品
JP2007228963A (ja) * 2006-02-02 2007-09-13 Ajinomoto Co Inc 血流改善作用を有する食品組成物
WO2009057725A1 (fr) * 2007-10-31 2009-05-07 Ito En, Ltd. Composition d'extrait de jute tossa traitée par une protéase, procédé de production de la composition et agent anti-hypertenseur ou boisson/aliment comprenant ladite composition
JP2010209084A (ja) * 2010-04-15 2010-09-24 Calpis Co Ltd アンジオテンシン変換酵素阻害剤
CN103054079A (zh) * 2012-08-09 2013-04-24 浙江省海洋开发研究院 一种鲐鱼鱼松的生产方法
JP2014141443A (ja) * 2013-01-25 2014-08-07 Ajinomoto Co Inc 血圧降下用アミノ酸含有組成物
WO2017002895A1 (fr) * 2015-07-01 2017-01-05 サントリーホールディングス株式会社 Composition comprenant un acide aminé et un dipeptide cyclique

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JPH01110695A (ja) * 1987-02-19 1989-04-27 Asahi Breweries Ltd アミノ酸誘導体その製造方法及び血圧降下剤
JPH0616568A (ja) * 1991-09-17 1994-01-25 Chiba Seifun Kk アンジオテンシン変換酵素阻害剤
JP2003081997A (ja) * 2001-03-27 2003-03-19 Tohoku Techno Arch Co Ltd 血圧降下作用があるペプチド

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JPH01110695A (ja) * 1987-02-19 1989-04-27 Asahi Breweries Ltd アミノ酸誘導体その製造方法及び血圧降下剤
JPH0616568A (ja) * 1991-09-17 1994-01-25 Chiba Seifun Kk アンジオテンシン変換酵素阻害剤
JP2003081997A (ja) * 2001-03-27 2003-03-19 Tohoku Techno Arch Co Ltd 血圧降下作用があるペプチド

Cited By (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2005206528A (ja) * 2004-01-23 2005-08-04 Calpis Co Ltd アンジオテンシン変換酵素阻害剤及び該阻害剤を含む食品
JP4605631B2 (ja) * 2004-01-23 2011-01-05 カルピス株式会社 アンジオテンシン変換酵素阻害剤
JP2007228963A (ja) * 2006-02-02 2007-09-13 Ajinomoto Co Inc 血流改善作用を有する食品組成物
WO2009057725A1 (fr) * 2007-10-31 2009-05-07 Ito En, Ltd. Composition d'extrait de jute tossa traitée par une protéase, procédé de production de la composition et agent anti-hypertenseur ou boisson/aliment comprenant ladite composition
JP2010209084A (ja) * 2010-04-15 2010-09-24 Calpis Co Ltd アンジオテンシン変換酵素阻害剤
CN103054079A (zh) * 2012-08-09 2013-04-24 浙江省海洋开发研究院 一种鲐鱼鱼松的生产方法
CN103054079B (zh) * 2012-08-09 2013-12-25 浙江省海洋开发研究院 一种鲐鱼鱼松的生产方法
JP2014141443A (ja) * 2013-01-25 2014-08-07 Ajinomoto Co Inc 血圧降下用アミノ酸含有組成物
WO2017002895A1 (fr) * 2015-07-01 2017-01-05 サントリーホールディングス株式会社 Composition comprenant un acide aminé et un dipeptide cyclique
CN107922458A (zh) * 2015-07-01 2018-04-17 三得利控股株式会社 含有氨基酸及环状二肽的组合物
AU2016285054B2 (en) * 2015-07-01 2020-07-02 Suntory Holdings Limited Composition comprising amino acid and cyclic dipeptide
CN107922458B (zh) * 2015-07-01 2022-01-21 三得利控股株式会社 含有氨基酸及环状二肽的组合物

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