Composition for suppressing blood pressure elevation

Abstract

The present invention relates to a composition for suppressing blood pressure elevation, the composition containing a protease decomposition product of phycocyanin.

Description

Composition for suppressing elevated blood pressure

[0001] The present disclosure relates to a composition for suppressing elevated blood pressure.

[0002] Angiotensin-converting enzyme (ACE, EC 3.4.15.1) is an enzyme that catalyzes the reaction in which inactive angiotensin I is converted into physiologically active angiotensin II (Patent Document 1).

[0003] Angiotensin II has a strong peripheral vasoconstrictor effect and also promotes the secretion of aldosterone produced in the adrenal cortex, which is known to induce an increase in blood pressure by excreting potassium from the blood and promoting sodium reabsorption, thereby increasing the water content of the blood (Non-Patent Document 1). Therefore, an increase in blood pressure can be suppressed by inhibiting angiotensin converting enzyme.

[0004] Known active ingredients for inhibiting angiotensin converting enzyme include, for example, specific compounds or salts thereof, or solvates thereof (Patent Document 1), specific tripeptides (Patent Document 2), and the like.

[0005] On the other hand, a pigment protein called phycocyanin is known, and compositions containing protease decomposition products of phycocyanin as active ingredients have been developed. For example, compositions for increasing muscle mass and suppressing its decline, compositions for increasing muscle mass and suppressing muscle atrophy (Patent Document 3), and compositions for improving memory and learning function and / or suppressing decline in cognitive function (Patent Document 4) are known.

[0006] International Publication No. WO 2016 / 111310 JP 2019-94271 A International Publication No. WO 2022 / 158503 International Publication No. WO 2022 / 158504

[0007] "Angiotensinogen," Ministry of Health, Labor and Welfare, Health Information Site for the Prevention of Lifestyle-Related Diseases, e-Health Net, Health Terminology Dictionary, Prevention of Lifestyle-Related Diseases, Angiotensinogen, [online], [Retrieved April 15, 2024], Internet <URL: https: / / www.e-healthnet.mhlw.go.jp / information / dictionary / metabolic / ym-008.html>

[0008] An object of the present disclosure is to provide a technology for inhibiting angiotensin-converting enzyme, and thereby a technology for suppressing an increase in blood pressure.

[0009] The present inventors have conducted extensive research to solve the above problems and have found that a protease digest of phycocyanin can solve the above problems.

[0010] The present disclosure can provide a composition for inhibiting angiotensin-converting enzyme, which contains a protease digest of phycocyanin as an active ingredient. The present disclosure can also provide a composition for suppressing hypertension, which contains a protease digest of phycocyanin as an active ingredient. The composition preferably inhibits angiotensin-converting enzyme. The composition preferably is a food or beverage composition. The composition preferably is a pharmaceutical composition. The composition preferably is a feed composition.

[0011] The present disclosure can provide a technique for inhibiting angiotensin-converting enzyme and a technique for suppressing an increase in blood pressure.

[0012] In the present disclosure, the terms "ingestion," "ingest," "ingested," etc. may be used interchangeably with the terms "administration," "administered," "administered," etc. The terms "administration," "administered," "administered," etc. may be terms used for, for example, feed compositions and pharmaceutical compositions.

[0013] One aspect of the present disclosure is a composition for inhibiting angiotensin-converting enzyme, which contains a protease degradation product of phycocyanin as an active ingredient.

[0014] The active ingredient contained in the composition of this embodiment is a protease decomposition product of phycocyanin.

[0015] Examples of phycocyanin in this embodiment include phycocyanin derived from algae. Specific examples include phycocyanin derived from blue-green algae, red algae, and cryptophyte algae. One or more of these may be used. Among these, blue-green algae-derived phycocyanin is preferred because it can be harvested in large quantities.

[0016] Examples of cyanobacteria include the genus Arthrospira (Spirulina), the genus Arthrospira, the genus Aphanizomenon, the genus Fisherella, the genus Anabaena, the genus Nostoc, and Synechocystis. Examples of cyanobacteria include those of the genus Synechocystis, Synechococcus, Tolypothrix, Aphanothece, Mastigoclaus, and Pleurocapsa, and one or more of these may be used. Among these, cyanobacteria of the genus Spirulina are preferred, as they are produced on an industrial scale and their safety has been confirmed. Cyanobacteria of the genus Arthrospira are also preferred. Cyanobacteria of the genus Spirulina are more preferred. Furthermore, fresh algae or dried algae may be used, and either one or both may be used. As the dried algal cells, raw algal cells may be dried according to a conventional method, or a commercially available dried product may be used. Alternatively, only one of these may be used, or both may be used.

[0017] Examples of phycocyanin include C-phycocyanin, R-phycocyanin, and allophycocyanin, and one or more of these may be used. From the viewpoints of quality, safety, and availability, C-phycocyanin is preferred. Also preferred are embodiments containing both C-phycocyanin and allophycocyanin.

[0018] Any known or commonly used method can be used for extracting phycocyanin without any particular limitations. For example, spirulina can be dried to destroy the cell walls and make it easier to extract, or frozen and thawed to destroy the cell walls and make it easier to extract, and then extracted with a solvent in which phycocyanin dissolves, such as water, a buffer solution, or alcohol. Alternatively, the phycocyanin extraction methods described in International Publication No. 2013 / 105430 (International Application No. PCT / JP2012 / 083471) and JP-A-2022-513061 may be used.

[0019] Furthermore, in order to extract high-purity phycocyanin, it is preferable to remove impurities from spirulina. Specifically, the extraction method described in the following extraction method (i) can be used. By using the following extraction method (i), high-purity phycocyanin with a vivid color tone can be obtained.

[0020] <<Phycocyanin Extraction Method (i)>> Extraction method (i) comprises the following steps: a first step of extracting phycocyanin from cyanobacteria into an aqueous suspension to obtain an extract; a second step of reacting a calcium salt with a phosphate salt in the extract to produce calcium phosphate and allowing the calcium phosphate to adsorb phycocyanin impurities to obtain an adsorbate; and a third step of removing cyanobacterial residues and the adsorbate from the extract.

[0021] Furthermore, it is more preferable that the above extraction method (i) is the following extraction method (ii). <<Phycocyanin Extraction Method (ii)>> Extraction method (ii) comprises the following steps: a first step of extracting phycocyanin from cyanobacteria into an aqueous suspension to obtain an extract; a second step of reacting a calcium salt with a phosphate salt in the extract to produce calcium phosphate and adsorbing phycocyanin impurities onto the calcium phosphate to obtain an adsorbate; a third step of removing cyanobacterial residues and adsorbates from the extract; and a step of adding a chelating agent to the extract prior to the third step.

[0022] By using the above-mentioned phycocyanin extraction method (i) or (ii), high-quality phycocyanin can be extracted from cyanobacteria. In particular, by using the above-mentioned extraction method (i) or (ii) for cyanobacteria of the genus Spirulina, high-quality phycocyanin with a good mixture ratio of C-phycocyanin to allophycocyanin can be extracted. In the above-mentioned extraction method, the mixture ratio of C-phycocyanin to allophycocyanin can be adjusted to a desired range by appropriately selecting the extraction conditions.

[0023] The phycocyanin may be entirely C-phycocyanin. Alternatively, allophycocyanin may be contained, and a mixture of C-phycocyanin and allophycocyanin may be contained in the composition. The mixing ratio of C-phycocyanin to allophycocyanin is, for example, preferably 3-9.5:0.5-7, more preferably 6-9.5:0.5-4, and even more preferably 7-8:2-3 by mass.

[0024] The form of the protease digest of phycocyanin is not limited as long as it has angiotensin-converting enzyme inhibitory activity. Furthermore, the greater the angiotensin-converting enzyme inhibitory activity, the more preferable it is. From these perspectives, the protease digest of phycocyanin may have, for example, the following molecular weight distribution. The "molecular weight" refers to the number-average molecular weight. The molecular weight distribution of the protease digest of phycocyanin in this embodiment is obtained by liquid chromatography using a gel filtration column under the following conditions, as in the Examples described below. The number-average molecular weight of the protease digest of phycocyanin in this embodiment is the number-average molecular weight calculated from the molecular weight distribution. (Liquid Chromatography Conditions) Column: TSKgel G2500PWXL, 7.8 x 300 mm (Tosoh) Column temperature: 40°C Eluent: 45% (v / v) acetonitrile containing 0.1% (v / v) formic acid Flow rate: 0.5 mL / min Detection wavelength: 220 nm

[0025] In the following, the following are given as examples: (a) the proportion of decomposition products with a molecular weight of 6,000 or more; (b) the proportion of decomposition products with a molecular weight of 3,000 or more but less than 6,000; and (c) the proportion of decomposition products with a molecular weight of less than 3,000 (which is also the sum of the proportion of decomposition products with a molecular weight of 1,000 or more but less than 3,000, the proportion of decomposition products with a molecular weight of 500 or more but less than 1,000, and the proportion of decomposition products with a molecular weight of less than 500). However, as long as there is no contradiction, such as the sum of (a), (b), and (c) exceeding 100%, one or more combinations of these may be used.

[0026] That is, for example, the protease decomposition product of phycocyanin may be such that the proportion of decomposition products with a molecular weight of 6,000 or more is 0% to 1% and the proportion of decomposition products with a molecular weight of less than 3,000 is 99% to 100%, and the total proportion does not exceed 100%. Also, for example, the proportion of decomposition products with a molecular weight of 6,000 or more is 0% to 1% and the proportion of decomposition products with a molecular weight of 3,000 to 6,000 is 0% to 1% and the proportion of decomposition products with a molecular weight of less than 3,000 is 99% to 100% (however, the proportion of decomposition products with a molecular weight of 1,000 to 3,000 is 5% to 10%), and the total proportion does not exceed 100%.

[0027] The protease decomposition products of phycocyanin have a proportion of decomposition products with a molecular weight of 6,000 or more of, for example, 65% or less, 60% or less, 55% or less, 50% or less, 45% or less, 40% or less, 35% or less, 30% or less, 25% or less, 20% or less, 15% or less, 14% or less, 13% or less, 12% or less, 11% or less, 10% or less, 9% or less, 8% or less, 7% or less, 6% or less, 5% or less, 4% or less, 3% or less, 2% or less, 1 ... % or less, etc., or alternatively, for example, 0% or more, 1% or more, 2% or more, 3% or more, 4% or more, 5% or more, 6% or more, 7% or more, 8% or more, 9% or more, 10% or more, 11% or more, 12% or more, 13% or more, 14% or more, 15% or more, 20% or more, 25% or more, 30% or more, 35% or more, 40% or more, 45% or more, 50% or more, 55% or more, 60% or more, etc., or 0%, or any combination thereof that does not contradict. For example, it may be 0% to 1%, 1% to 2%, 2% to 3%, 3% to 4%, 4% to 5%, 5% to 6%, 6% to 7%, 7% to 8%, 8% to 9%, 9% to 10%, 10% to 11%, 11% to 12%, 12% to 13%, 13% to 14%, 14% to 15%, 15% to 20%, 20% to 25%, 25% to 30%, 30% to 35%, 35% to 40%, 40% to 45%, 45% to 50%, 50% to 55%, 55% to 60%, 60% to 65%, etc.

[0028] Furthermore, the proportion of protease decomposition products of phycocyanin with a molecular weight of 3,000 or more but less than 6,000 may be, for example, 0% or more, 1% or more, 2% or more, 3% or more, 4% or more, 5% or more, 6% or more, 7% or more, 8% or more, 9% or more, etc., or, for example, 10% or less, 9% or less, 8% or less, 7% or less, 6% or less, 5% or less, 4% or less, 3% or less, 2% or less, 1% or less, etc., or even 0%. A consistent combination thereof is also acceptable. For example, it may be 0% to 1% or less, 1% to 2% or less, 2% to 3% or less, 3% to 4% or less, 4% to 5% or less, 5% to 6% or less, 6% to 7% or less, 7% to 8% or less, 8% to 9% or less, 9% to 10% or less, etc.

[0029] Furthermore, the proportion of protease decomposition products of phycocyanin with a molecular weight of less than 3,000 is, for example, 25% or more, 30% or more, 35% or more, 40% or more, 45% or more, 50% or more, 55% or more, 60% or more, 65% or more, 70% or more, 75% or more, 80% or more, 81% or more, 82% or more, 83% or more, 84% or more, 85% or more, 86% or more, 87% or more, 88% or more, 89% or more, 90% or more, 91% or more, 92% or more, 93% or more, 94% or more, 95% or more, 96% or more, 97% or more, 98% or more, 99% or more, % or more, etc., or, for example, 100% or less, 99% or less, 98% or less, 97% or less, 96% or less, 95% or less, 94% or less, 93% or less, 92% or less, 91% or less, 90% or less, 89% or less, 88% or less, 87% or less, 86% or less, 85% or less, 84% or less, 83% or less, 82% or less, 81% or less, 80% or less, 75% or less, 70% or less, 65% or less, 60% or less, 55% or less, 50% or less, 45% or less, 40% or less, 35% or less, 30% or less, etc., or 100%. Any consistent combination thereof is also acceptable. For example, 25% to 30%, 30% to 35%, 35% to 40%, 40% to 45%, 45% to 50%, 50% to 55%, 55% to 60%, 60% to 65%, 65% to 70%, 70% to 75%, 75% to 80%, 80% to 81%, 81% to 82%, 82% to 83%, 83% to 84%, 84% to 85% %, 85% to 86%, 86% to 87%, 87% to 88%, 88% to 89%, 89% to 90%, 90% to 91%, 91% to 92%, 92% to 93%, 93% to 94%, 94% to 95%, 95% to 96%, 96% to 97%, 97% to 98%, 98% to 99%, 99% to 100%, etc.

[0030] Furthermore, the proportion of protease decomposition products of phycocyanin with a molecular weight of 1,000 to less than 3,000 may be, for example, 0% or more, 1% or more, 5% or more, 10% or more, 15% or more, 20% or more, 25% or more, 30% or more, 35% or more, 40% or more, etc., or, for example, 45% or less, 40% or less, 35% or less, 30% or less, 25% or less, 20% or less, 15% or less, 10% or less, 5% or less, 1% or less, etc., or even 0%. A consistent combination thereof is also acceptable. For example, it may be 0% to 1%, 1% to 5%, 5% to 10%, 10% to 15%, 15% to 20%, 20% to 25%, 25% to 30%, 30% to 35%, 35% to 40%, 40% to 45%, etc.

[0031] Furthermore, the proportion of protease decomposition products of phycocyanin with a molecular weight of 500 or more but less than 1,000 is, for example, 0% or more, 5% or more, 10% or more, 15% or more, 20% or more, 25% or more, 30% or more, 35% or more, 40% or more, 45% or more, 50% or more, 55% or more, 56% or more, 57% or more, 58% or more, 59% or more, 60% or more, 61% or more, 62% or more, 63% or more, 64% or more, 65% or more, 66% or more, 67% or more, 68% or more, 69% or more, 70% or more, 71% or more, 72% or more, 73% or more , 74% or more, etc., or, for example, 75% or less, 74% or less, 73% or less, 72% or less, 71% or less, 70% or less, 69% or less, 68% or less, 67% or less, 66% or less, 65% or less, 64% or less, 63% or less, 62% or less, 61% or less, 60% or less, 59% or less, 58% or less, 57% or less, 56% or less, 55% or less, 50% or less, 45% or less, 40% or less, 35% or less, 30% or less, 25% or less, 20% or less, 15% or less, 10% or less, 5% or less, etc., or 0%. Any consistent combination thereof is also acceptable. For example, 0% to 5%, 5% to 10%, 10% to 15%, 15% to 20%, 20% to 25%, 25% to 30%, 30% to 35%, 35% to 40%, 40% to 45%, 45% to 50%, 50% to 55%, 55% to 56%, 56% to 57%, 57% to 58%, 58% to 59%, 59% to 60% , 60% to 61%, 61% to 62%, 62% to 63%, 63% to 64%, 64% to 65%, 65% to 66%, 66% to 67%, 67% to 68%, 68% to 69%, 69% to 70%, 70% to 71%, 71% to 72%, 72% to 73%, 73% to 74%, 74% to 75%, etc.

[0032] Furthermore, the proportion of protease decomposition products of phycocyanin with a molecular weight of less than 500 may be, for example, 0% or more, 1% or more, 5% or more, 10% or more, 15% or more, 20% or more, 25% or more, 30% or more, 35% or more, 40% or more, 45% or more, 50% or more, 55% or more, etc., or, for example, 60% or less, 55% or less, 50% or less, 45% or less, 40% or less, 35% or less, 30% or less, 25% or less, 20% or less, 15% or less, 10% or less, 5% or less, 1% or less, etc., or 0%. A consistent combination thereof is also possible. For example, it may be 0% to 1%, 1% to 5%, 5% to 10%, 10% to 15%, 15% to 20%, 20% to 25%, 25% to 30%, 30% to 35%, 35% to 40%, 40% to 45%, 45% to 50%, 50% to 55%, 55% to 60%, etc.

[0033] The type of protease is not limited as long as the decomposition product obtained by decomposing phycocyanin has angiotensin converting enzyme inhibitory activity. Furthermore, the more the decomposition product obtained by decomposing phycocyanin has angiotensin converting enzyme inhibitory activity, the more preferable it is.

[0034] From these viewpoints, examples of proteases include proteases derived from microorganisms (e.g., bacteria), mammalian proteases, and plant proteases, and one or more of these may be used.

[0035] Examples of the enzyme include endoproteases, exoproteases, endo / exoprotease complex enzymes, exopeptidase / endoprotease complex enzymes, and protease / peptidase complex enzymes, and one or more of these may be used.

[0036] The protease used in the present disclosure may also be referred to as a peptidase.

[0037] Examples of the microorganisms used in proteases derived from microorganisms (e.g., bacteria) include microorganisms belonging to the genus Aspergillus, Bacillus, Streptomyces, Geobacillus, and Rhizopus.

[0038] Examples of microorganisms belonging to the genus Aspergillus include microorganisms belonging to Aspergillus melleus, microorganisms belonging to Aspergillus niger, and microorganisms belonging to Aspergillus oryzae. Commercially available products include, for example, the following: "Proteax (Amano Enzyme Co., Ltd.)" and "Protease M "Amano" SD (Amano Enzyme Co., Ltd.)," which are proteases derived from microorganisms belonging to the genus Aspergillus (Aspergillus sp.); and "Sumiteam AP (Shin Nippon Chemical Industry Co., Ltd.)" and "MAXIPRO PSP (DSM)," which are proteases derived from microorganisms belonging to Aspergillus niger. Examples of such proteases include "Sumiteam LP (Shin Nippon Chemical Industry Co., Ltd.)," "Protease A "Amano" SD (Amano Enzyme Co., Ltd.)," "Coclase-P Granules (Mitsubishi Chemical Corporation)," "Sumiteam ACP-G (Shin Nippon Chemical Industry Co., Ltd.)," "Sumiteam DPP-G (Shin Nippon Chemical Industry Co., Ltd.)," and "Sumiteam FLAP (Shin Nippon Chemical Industry Co., Ltd.)," which are proteases derived from microorganisms belonging to Aspergillus oryzae. Examples of such proteases include "Protease P "Amano" 3SD (Amano Enzyme Co., Ltd.)," which is a protease derived from microorganisms belonging to Aspergillus melleus.

[0039] Examples of microorganisms belonging to the genus Bacillus include microorganisms belonging to Bacillus licheniformis, microorganisms belonging to Bacillus subtillus, microorganisms belonging to Bacillus amyloliquefaciens, and microorganisms belonging to Bacillus polymyxa. Commercially available products include, for example, the following: "Protin SD-AY10 (Amano Enzyme Inc.)" and "Protin SD-NY10 (Amano Enzyme Inc.)," ​​which are proteases derived from microorganisms (Bacillus sp.) belonging to the genus Bacillus. Examples include "Alcalase 2.4 LFG (Novozymes Co., Ltd.)" and "Bioprase SP-20FG (Nagase ChemteX Corporation)," which are proteases derived from microorganisms belonging to Bacillus licheniformis. Examples include "Sumiteam BNP (Shin Nippon Chemical Industry Co., Ltd.)," which is a protease derived from microorganisms belonging to Bacillus subtilis. Examples include "Neutrase (Novozymes Co., Ltd.)," which is a protease derived from microorganisms belonging to Bacillus amyloliquefaciens.

[0040] Examples of microorganisms belonging to the genus Streptomyces include microorganisms belonging to Streptomyces caespitosus and microorganisms belonging to Streptomyces griseus. Commercially available products include, for example, the following: Denatym CPO PEPRICH (Nagase ChemteX Corporation) and Denatym PMC SOFTER (Nagase ChemteX Corporation), which are proteases derived from microorganisms belonging to the genus Streptomyces (Streptomyces sp.).

[0041] Examples of microorganisms belonging to the genus Geobacillus include microorganisms belonging to Geobacillus stearothermophilus. Commercially available products include, for example, the following: "Thermoase PC10F (Amano Enzyme Co., Ltd.)," a protease derived from a microorganism (Geobacillus sp.) belonging to the genus Geobacillus.

[0042] Examples of microorganisms belonging to the genus Rhizopus include microorganisms belonging to Rhizopus niveus. Commercially available products include, for example, the following: "Neurase F3G (Amano Enzyme Inc.)" and "Peptidase R (Amano Enzyme Inc.)," ​​which are proteases derived from microorganisms belonging to the genus Rhizopus (Rhizopus sp.).

[0043] Further examples of proteases derived from microorganisms (e.g., bacteria) include "Protamex (Novozymes Inc.)," ​​which is a mixture of two types of microorganisms (Bacillus sp.) belonging to the genus Bacillus. Further examples of proteases derived from microorganisms (e.g., bacteria) include, in addition to the above, "Formia CTL Formiasol (Novozymes Inc.)" and "Formia TL Formia Prime (Novozymes Inc.)."

[0044] Examples of mammalian proteases include porcine proteases, bovine proteases, and equine proteases. Examples of porcine proteases include porcine pancreatic proteases and porcine gastric mucosa proteases. Commercially available products include the following: "Pancreatin F (Amano Enzyme Inc.)," ​​a porcine pancreatic protease, and "Pepsibio 1:10,000 (Japan Biocon Co., Ltd.)," a porcine gastric mucosa protease.

[0045] Examples of plant-derived proteases include papaya-derived proteases and pineapple-derived proteases. Examples of papaya-derived proteases include proteases derived from the milk of unripe papaya fruits. Examples of pineapple-derived proteases include proteases derived from pineapple stems. Examples of commercially available products include the following: "Papain 300 (Nippon Biocon Co., Ltd.)," which is a protease derived from the milk of unripe papaya fruits, and "Bromelain 200 GDU (Nippon Biocon Co., Ltd.)," which is a protease derived from pineapple stems.

[0046] Angiotensin-converting enzyme inhibitory activity can be measured by a conventional method. For example, it can be measured as an ACE inhibitory activity value (%) using a commercially available ACE inhibitory activity measurement kit (Dojindo Laboratories, product code: A502 ACE Kit-WST) according to the instruction manual. A higher ACE inhibitory activity value (%) indicates a higher ACE inhibitory activity.

[0047] The angiotensin converting enzyme inhibitory activity in this embodiment is, for example, as an ACE inhibitory activity value (%), in order of increasing preference, 50% or more, 55% or more, 60% or more, 65% or more, 70% or more, 75% or more, 80% or more, 81% or more, 82% or more, 83% or more, 84% or more, 85% or more, 86% or more, 87% or more, 88% or more, 89% or more, 90% or more, 91% or more, 92% or more, 93% or more, 94% or more, 95% or more, 96% or more, 97% or more, 98% or more, 99% or more, 100% or more, 101% or more, 102% or more, 103% or more, 104% or more, 105% or more, 106% or more, 107% or more, 108% or more, 109% or more, 110% or more, 111% or more, 112% or more, 113% or more, 114% or more, 115% or more, 116% or more, 117% or more, 118% or more, 119% or more, 120% or more, 121% or more, 122% or more, 123% or more, 124% or more, 125% or more, 126% or more, 127% or more, 128% or more, 129% or more, 130% or more, 131% or more, 132% or more, 133% or more, 134% or more, 135% or more, 136% 9% or more, while a larger upper limit is preferable, but examples include 100% or less, 99% or less, 98% or less, 97% or less, 96% or less, 95% or less, 94% or less, 93% or less, 92% or less, 91% or less, 90% or less, 89% or less, 88% or less, 87% or less, 86% or less, 85% or less, 84% or less, 83% or less, 82% or less, 81% or less, 80% or less, 75% or less, 70% or less, 65% or less, 60% or less, 55% or less, and may also be 100%. Consistent combinations of these are also acceptable. For example, 50% to 55%, 55% to 60%, 60% to 65%, 65% to 70%, 70% to 75%, 75% to 80%, 80% to 81%, 81% to 82%, 82% to 83%, 83% to 84%, 84% to 85%, 85% to 86%, 86% to 87%, 87% to 88%, 88% to 89%, 89% to 90%, 90% to 91%, 91% to 92%, 92% to 93%, 93% to 94%, 94% to 95%, 95% to 96%, 96% to 97%, 97% to 98%, 98% to 99%, 99% to 100%, etc.

[0048] The composition of this embodiment may contain the active ingredient alone, or may contain, as another ingredient, an ingredient that exhibits an angiotensin-converting enzyme inhibitory effect when in the form of a composition. When the composition of this embodiment contains such an ingredient, the composition of this embodiment may be a mixture of the active ingredient and such an ingredient, and these ingredients may be homogeneous or heterogeneous.

[0049] The subject to be ingested with the composition of this embodiment may be a mammal. Mammals include humans and non-human mammals. Non-human mammals include, for example, pet animals and livestock animals, more specifically, cows, horses, goats, sheep, pigs, monkeys, dogs, cats, rats, mice, hamsters, guinea pigs, etc.

[0050] The composition of this embodiment has angiotensin-converting enzyme inhibitory activity and can be used to prevent or treat diseases, signs, symptoms, or disorders that can be prevented or treated by inhibiting angiotensin-converting enzyme (in the present disclosure, "diseases, signs, symptoms, or disorders" may be referred to as "diseases, etc."). The subject may have one or more diseases, signs, symptoms, or disorders. Examples of such diseases, etc. include hypertension and heart failure.

[0051] The use of the composition of this embodiment may be for non-therapeutic purposes or for therapeutic purposes. "Non-therapeutic purposes" are purposes that do not include medical procedures. In other words, purposes that do not include treatment of a subject through therapy. Examples include uses for maintaining or promoting health.

[0052] When the composition of this embodiment is used for non-therapeutic purposes, it can be targeted at healthy individuals. A "healthy individual" may be an individual who, at the time of ingesting the composition of this embodiment, does not have a disease that can be prevented or treated by inhibiting angiotensin-converting enzyme, an individual who is concerned about the disease, an individual who is at risk of the disease, or the like. When the composition of this embodiment is used for non-therapeutic purposes, it becomes possible to prevent the disease in healthy individuals.

[0053] When the composition of this embodiment is used for therapeutic purposes, the target may be an unhealthy individual. The "unhealthy individual" may be a person who, at the time of ingesting the composition of this embodiment, suffers from a disease that can be treated by inhibiting angiotensin-converting enzyme. When the composition of this embodiment is used for therapeutic purposes, the disease can be treated in the unhealthy individual.

[0054] The total content of the active ingredient in the composition of this embodiment is appropriately set depending on the embodiment of the composition, but is, for example, 20% by mass or more, 50% by mass or more, or, for example, 100% by mass or less, 99% by mass or less, calculated on a dry weight basis of the active ingredient. It may also be any compatible combination thereof, such as 20% by mass to 100% by mass or 50% by mass to 99% by mass.

[0055] The total intake amount (effective amount) of the composition of this embodiment is appropriately determined depending on the form of the composition, the method of use, the subject, the subject's age, sex, and other conditions, but is not particularly limited as long as the angiotensin-converting enzyme inhibitory effect or subsequent effects are exhibited in the subject who ingests it, and is, for example, 0.01 g or more, 0.03 g or more, or, for example, 10 g or less, 4 g or less, per 60 kg body weight, calculated as the dry weight of the active ingredient. A consistent combination thereof is also acceptable, for example, 0.01 g to 10 g, 0.03 g to 4 g or less, etc.

[0056] The composition of this embodiment can be taken once a day or in divided doses. It may also be taken once every few days or weeks, but is preferably taken daily. For example, daily intake for 4 or more days, daily intake for 5 or more days, daily intake for 7 or more days, daily intake for 14 or more days, daily intake for 21 or more days, daily intake for 28 or more days, etc.

[0057] The composition of this embodiment can be taken orally, nasally, or via a gastrostomy or enterostomy.

[0058] The composition of this embodiment can be used, for example, as a food or beverage composition, a feed composition, a pharmaceutical composition, etc. For example, it can be provided as a "food or beverage composition for angiotensin-converting enzyme inhibition, containing a protease digest of phycocyanin as an active ingredient." Hereinafter, this may be referred to as the "food or beverage composition of this embodiment." The "food or beverage composition of this embodiment" includes supplements. It can also be provided as a "feed composition for angiotensin-converting enzyme inhibition, containing a protease digest of phycocyanin as an active ingredient." Hereinafter, this may be referred to as the "feed composition of this embodiment." It can also be provided as a "pharmaceutical composition for angiotensin-converting enzyme inhibition, containing a protease digest of phycocyanin as an active ingredient." Hereinafter, this may be referred to as the "pharmaceutical composition of this embodiment."

[0059] When the active ingredient is used as a material for the food and drink composition of this embodiment, it can be used as a general food and drink composition, as well as a food for specified health uses, a nutritional supplement, a functional food, a food for the sick, a food additive, etc. (These also include beverages.) As for the form of the food and drink composition, for example, after adding an appropriate auxiliary agent, it may be formed into an edible form, such as granules, particles, tablets, capsules, paste, etc. using conventional means and then provided for consumption, or it may be added to various foods, for example, processed meat foods such as ham and sausage, processed seafood foods such as kamaboko and chikuwa, bread, confectionery, butter, powdered milk, fermented dairy products, or beverages such as water, fruit juice, milk, and soft drinks.

[0060] The food and beverage composition of this embodiment can be administered to any subject, including healthy and unhealthy individuals, but in the case of a food and beverage composition labeled for a specific use (particularly a health use) or function, it may be used for the above-mentioned non-therapeutic purposes.

[0061] The food and beverage composition of this embodiment can contain, as its main components, water, proteins, carbohydrates, lipids, vitamins, minerals, organic acids, organic bases, fruit juice, flavors, etc. Examples of proteins include animal and vegetable proteins such as whole milk powder, skim milk powder, partially skim milk powder, casein, soy protein, egg protein, and meat protein, as well as hydrolysates thereof, and butter. Examples of carbohydrates include sugars, modified starch (dextrin, soluble starch, British starch, oxidized starch, starch ester, starch ether, etc.), dietary fiber, etc. Examples of lipids include vegetable oils and fats such as lard, safflower oil, corn oil, rapeseed oil, palm oil, fractionated oils thereof, hydrogenated oils, and interesterified oils. Examples of vitamins include vitamin A, carotenes, B vitamins, vitamin C, D vitamins, vitamin E, K vitamins, vitamin P, vitamin Q, niacin, nicotinic acid, pantothenic acid, biotin, inositol, choline, and folic acid. Examples of minerals include calcium, potassium, magnesium, sodium, copper, iron, manganese, zinc, selenium, and whey minerals. Examples of organic acids include malic acid, citric acid, lactic acid, and tartaric acid.

[0062] The food and beverage composition of this embodiment can be produced according to a conventional method. For example, it can be produced by adding the active ingredient to ordinary raw materials for a food and beverage composition. Except for the addition of the active ingredient, it can be produced in the same manner as ordinary food and beverage compositions. Furthermore, the amount, method, and timing of the active ingredient can be selected appropriately. Furthermore, the food and beverage composition of this embodiment can be sealed in an appropriate container such as a bottle, bag, can, box, or pack, as needed.

[0063] The total content of the active ingredient in the food and beverage composition of this embodiment is appropriately set depending on the embodiment of the food and beverage composition, but is, for example, 20% by mass or more, 50% by mass or more, or, for example, 100% by mass or less, 99% by mass or less, calculated on a dry weight basis of the active ingredient. It may also be any compatible combination thereof, such as 20% by mass to 100% by mass, 50% by mass to 99% by mass, etc.

[0064] The total intake amount (effective amount) of the food and beverage composition of this embodiment is appropriately determined depending on the form of the food and beverage composition, the method of use, the subject, the subject's age, sex, and other conditions, but is not particularly limited as long as the angiotensin-converting enzyme inhibitory effect or subsequent effects are exhibited in the subject who ingests it, and is, for example, 0.01 g or more, 0.03 g or more, or, for example, 10 g or less, 4 g or less, per 60 kg body weight, calculated as the dry weight of the active ingredient. A consistent combination thereof is also acceptable, for example, 0.01 g to 10 g, 0.03 g to 4 g or less, etc.

[0065] The food and drink composition of this embodiment can be taken once a day or in divided doses. It may also be taken once every few days or weeks, but is preferably taken daily. For example, daily intake for 4 days or more, daily intake for 5 days or more, daily intake for 7 days or more, daily intake for 14 days or more, daily intake for 21 days or more, daily intake for 28 days or more, etc.

[0066] When the subject is a mammal other than a human, the active ingredient can be used as an ingredient in the feed composition of this embodiment. In this case, the feed ingredients and the active ingredient can be appropriately mixed depending on the type of mammal, developmental stage, region, and other rearing environments. Examples of feed ingredients include grains or processed grains (corn, milo, barley, etc.), bran (bran, rice bran, corn gluten feed, etc.), vegetable oil cakes (soybean oil cake, sesame oil cake, cottonseed oil cake, etc.), animal ingredients (skim milk powder, fish meal, meat and bone meal, etc.), minerals (calcium carbonate, calcium phosphate, salt, silicic acid anhydride, etc.), vitamins, amino acids, yeasts such as brewer's yeast, and inorganic powders (crystalline cellulose, talc, silica, etc.).

[0067] The feed composition of this embodiment may contain, in addition to the above-mentioned feed raw materials, feed additives commonly used in compound feeds, such as excipients, bulking agents, binders, thickeners, emulsifiers, coloring agents, flavorings, food additives, and seasonings, as well as other ingredients (antibiotics, disinfectants, anthelmintics, preservatives, etc.) as desired.

[0068] The form of the feed composition of this embodiment is not particularly limited, and examples thereof include powder, granules, paste, pellets, capsules (hard capsules, soft capsules), tablets, etc., and the feed composition may be used as pet food for companion animals or feed for laboratory animals.

[0069] The total content of the active ingredients in the feed composition of this embodiment is appropriately determined depending on the embodiment of the feed composition, but is, for example, 20% by mass or more, 50% by mass or more, or, for example, 100% by mass or less, 99% by mass or less, calculated on a dry weight basis of the active ingredients. It may also be any compatible combination thereof, such as 20% to 100% by mass or 50% to 99% by mass.

[0070] The total dose (effective amount) of the feed composition of this embodiment is appropriately determined depending on the form of the feed composition, the method of use, the subject, the subject's age, sex, and other conditions, but is not particularly limited as long as the angiotensin-converting enzyme inhibitory effect or subsequent effects are exhibited in the subject to which it is administered. The total dose is, for example, 0.01 g or more, 0.03 g or more, or, for example, 10 g or less, 4 g or less, per 60 kg body weight, calculated as the dry weight of the active ingredient. A consistent combination thereof is also acceptable, for example, 0.01 g to 10 g, 0.03 g to 4 g or less, etc.

[0071] The feed composition of this embodiment can be administered once a day or in divided doses. It may also be administered once every few days or weeks, but daily administration is preferred. Examples of daily administration include administration for 4 or more days, 5 or more days, 7 or more days, 14 or more days, 21 or more days, and 28 or more days.

[0072] When the active ingredient is used as a material for the pharmaceutical composition of this embodiment, the pharmaceutical composition can be administered orally or parenterally. For administration, the active ingredient can be mixed with a solid or liquid non-toxic pharmaceutical carrier suitable for oral, rectal, or injection administration, and administered in the form of a conventional pharmaceutical formulation. Examples of such formulations include solids such as tablets, granules, powders, and capsules; liquids such as solutions, suspensions, and emulsions; and lyophilized preparations. These formulations can be prepared by conventional pharmaceutical methods. Examples of the non-toxic pharmaceutical carrier include glucose, lactose, sucrose, starch, mannitol, dextrin, fatty acid glycerides, polyethylene glycol, hydroxyethyl starch, ethylene glycol, polyoxyethylene sorbitan fatty acid esters, amino acids, gelatin, albumin, water, and physiological saline. Conventional additives such as stabilizers, humectants, emulsifiers, binders, and isotonicity agents can also be added as needed.

[0073] The pharmaceutical composition of this embodiment is administered to unhealthy subjects and used for the above-mentioned therapeutic purposes.

[0074] The total content of the active ingredient in the pharmaceutical composition of this embodiment is appropriately set depending on the embodiment of the pharmaceutical composition, but is, for example, 20% by mass or more, 50% by mass or more, or, for example, 100% by mass or less, 99% by mass or less, calculated as the dry weight of the active ingredient. It may also be any compatible combination thereof, such as 20% by mass to 100% by mass, 50% by mass to 99% by mass, etc.

[0075] The total dose (effective amount) of the pharmaceutical composition of this embodiment is appropriately determined depending on the form of the pharmaceutical composition, the dosage, the subject, the subject's age, sex, and other conditions, but is not particularly limited as long as the angiotensin-converting enzyme inhibitory effect or subsequent effects are exhibited in the subject to which it is administered, and is, for example, 0.01 g or more, 0.03 g or more, or, for example, 10 g or less, 4 g or less, per 60 kg body weight, calculated in terms of the dry weight of the active ingredient. It may also be a compatible combination thereof, for example, 0.01 g to 10 g, 0.03 g to 4 g or less, etc.

[0076] The pharmaceutical composition of this embodiment can be administered once a day or in divided doses. It may also be administered once every few days or weeks, but daily administration is preferred. Examples of such administration include daily administration for 4 or more days, daily administration for 5 or more days, daily administration for 7 or more days, daily administration for 14 or more days, daily administration for 21 or more days, and daily administration for 28 or more days.

[0077] Another aspect of the present disclosure is a composition for suppressing hypertension, which contains a protease degradation product of phycocyanin as an active ingredient.

[0078] As described in the Background Art, the inhibition of angiotensin-converting enzyme suppresses an increase in blood pressure. For this embodiment, the explanation of the "composition for inhibiting angiotensin-converting enzyme containing a protease-decomposed product of phycocyanin as an active ingredient" according to the previous embodiment is incorporated herein by reference.

[0079] In addition to the above-mentioned aspects, the present disclosure can also provide the following aspects, for example: Use of the active ingredient for producing a composition for inhibiting angiotensin-converting enzyme. The active ingredient for use in the prevention or treatment of diseases, etc. that can be prevented or treated by inhibiting angiotensin-converting enzyme. Use of the active ingredient in the production of a prophylactic or therapeutic drug for diseases, etc. that can be prevented or treated by inhibiting angiotensin-converting enzyme. A composition containing the active ingredient for use in the prevention or treatment of diseases, etc. that can be prevented or treated by inhibiting angiotensin-converting enzyme. Non-therapeutic use of the active ingredient, where the active ingredient is used for the prevention of diseases, etc. that can be prevented by inhibiting angiotensin-converting enzyme. Non-therapeutic use of a composition containing the active ingredient, where the composition is used for the prevention of diseases, etc. that can be prevented by inhibiting angiotensin-converting enzyme. A method for preventing or treating diseases, etc. that can be prevented or treated by inhibiting angiotensin-converting enzyme, comprising administering a prophylactically effective amount or therapeutically effective amount of the active ingredient to a subject in need of prevention or treatment. A method for preventing or treating a disease that can be prevented or treated by inhibiting angiotensin-converting enzyme, comprising administering a prophylactically effective amount or a therapeutically effective amount of a composition containing the active ingredient to a subject in need of prevention or treatment.

[0080] In addition to the above-mentioned aspects, the present disclosure can also provide the following aspects, for example: Use of the active ingredient for producing a composition for suppressing blood pressure increase. The active ingredient for use in the prevention or treatment of diseases, etc. that can be prevented or treated by suppressing blood pressure increase. Use of the active ingredient in the production of a prophylactic or therapeutic drug for diseases, etc. that can be prevented or treated by suppressing blood pressure increase. A composition containing the active ingredient for use in the prevention or treatment of diseases, etc. that can be prevented or treated by suppressing blood pressure increase. Non-therapeutic use of the active ingredient, in which the active ingredient is used for the prevention of diseases, etc. that can be prevented by suppressing blood pressure increase. Non-therapeutic use of a composition containing the active ingredient, in which the composition is used for the prevention of diseases, etc. that can be prevented by suppressing blood pressure increase. A method for preventing or treating diseases, etc. that can be prevented or treated by suppressing blood pressure increase, comprising administering a prophylactically effective amount or therapeutically effective amount of the active ingredient to a subject in need of prevention or treatment. A method for preventing or treating a disease that can be prevented or treated by suppressing blood pressure elevation, comprising administering a prophylactically effective amount or a therapeutically effective amount of a composition containing the active ingredient to a subject in need of prevention or treatment.

[0081] The present disclosure will be specifically described below using examples, but the present disclosure is not limited to these examples.

[0082] Test Example 1 (Extraction of Spirulina) Spirulina platensis was grown in an outdoor culture pond under basic conditions (pH 11). Next, 50 g of spray-dried algal powder of the grown Spirulina platensis was suspended in 500 mL of distilled water in an autoclave, and extracted for 1 hour at an extraction temperature of 120°C by adjusting the pressure. The pH of the extract was adjusted to 4.0 with citric acid. The extract was centrifuged to remove algal residue and protein (insoluble fraction), yielding a spirulina extract, which was a hot water extract of spirulina. The resulting spirulina extract was spray-dried and then crushed to obtain powdered spirulina.

[0083] (Phycocyanin Extraction) 65 kg of dried Spirulina algae (spray-dried product) produced in an outdoor culture tank was added to 1300 L of 1% calcium chloride (anhydrous) solution, and the mixture was stirred for 15 minutes to form a uniform suspension. The suspension was then left to stand at 20°C for 15 hours to extract the phycocyanin from the cyanobacteria. 32 kg of sodium dihydrogen phosphate was added to the extract, which was then stirred for 0.5 hours and then left to stand at 20°C for 2.5 hours to produce calcium phosphate, which adsorbed phycocyanin impurities to the calcium phosphate, yielding an adsorbate. The extract was then centrifuged at a gravitational acceleration of 10,000 G for 15 minutes to remove the cyanobacteria residue and adsorbed materials from the extract. The obtained phycocyanin extract was subjected to ultrafiltration using a separation membrane with a molecular weight cutoff of 10,000 to remove low-molecular-weight components and salts, after which trehalose and trisodium citrate were added, mixed, and spray-dried to obtain 15 kg of dried phycocyanin pigment. This was designated phycocyanin. The phycocyanin content was approximately 30% by mass (C-phycocyanin: approximately 22% by mass, allophycocyanin: approximately 8% by mass) of 100% by mass of phycocyanin pigment powder.

[0084] (Preparation of Protease Decomposition Products of Phycocyanin) Phycocyanin protease decomposition products were prepared as follows. Phycocyanin was decomposed using the proteases listed in Tables 1, 2, and 3 at the temperatures and pHs listed in the tables, followed by centrifugation at 2,000 × g for 3 minutes, and the supernatant was recovered. Specifically, phycocyanin was added to water to a concentration of 3% by mass, and the pH of the resulting phycocyanin aqueous solution was adjusted to the pH listed in the tables. Next, 3% by mass of enzyme (based on the phycocyanin) was added, and the mixture was stirred for 3, 6, or 20 hours at the temperatures listed in the tables to decompose the phycocyanin. The enzyme was then inactivated or heated or cooled to terminate the enzymatic degradation. The mixture was then centrifuged at 2,000 × g for 3 minutes, and the supernatant was recovered. The resulting supernatant was concentrated to dryness or lyophilized to obtain a protease decomposition product of phycocyanin.

[0085] The resulting protease-digested phycocyanin was redissolved in water to prepare samples for use in the "measurement of angiotensin-converting enzyme inhibitory activity" described below. Tables 1, 2, and 3 show the results after protease treatment for 3, 6, and 20 hours, respectively.

[0086] The molecular weight distribution of the protease digest was obtained by liquid chromatography using a gel filtration column under the following conditions: (Liquid Chromatography Conditions) Column: TSKgel G2500PWXL, 7.8 x 300 mm (Tosoh Corporation) Column temperature: 40°C Eluent: 45% (v / v) acetonitrile containing 0.1% (v / v) formic acid Flow rate: 0.5 mL / min Detection wavelength: 220 nm

[0087] A negative control was prepared in the same manner as above except that the phycocyanin was not treated with the protease.

[0088] (Measurement of Angiotensin-Converting Enzyme Inhibitory Activity) Using a commercially available ACE inhibitory activity measurement kit (Dojindo Laboratories, product code: A502 ACE Kit-WST), the ACE inhibitory activity (%) of the sample prepared above was measured according to the manual. Note that the following test examples show results of n=1 to 4.

[0089] (Results) The results are shown in Tables 1, 2 and 3. For the negative control, the ACE inhibitory activity value (%) was 20.59, with a standard error of 2.77.

[0090]

[0091]

[0092]

[0093] <Test Example 2> A part of the protease decomposition product of phycocyanin prepared in Test Example 1 was used as a test substance to examine the effect of the test substance on blood pressure.

[0094] (Spontaneous Hypertension Model) Male rats of the "SHR / Izm" strain (Japan SLC Co., Ltd.), a model of spontaneous hypertension, were used. After arrival at 8 weeks of age, rats were subjected to an 8-day quarantine and acclimation period. During the quarantine and acclimation period, general conditions were observed once daily, and body weights were measured the day after arrival and on the day of completion of quarantine and acclimation. Based on blood pressure and body weight on the day of acclimation, 25 rats were selected and assigned to five groups using a computer-assisted complete random sampling method, ensuring equal mean values ​​for each group. Rats were allowed free access to commercially available solid feed (trade name "MF"; Oriental Yeast Co., Ltd.). Tap water was available via a water bottle.

[0095] (Test Substances) The test substances used were the protease hydrolysates of phycocyanin prepared in Test Example 1, including a papaya milk-derived enzymatic hydrolysate of phycocyanin (using No. 2-4 "Papain 300"; Group A2), a Bacillus-derived enzymatic hydrolysate of phycocyanin (using No. 2-22 "Protin SD-NY10"; Group A3), a Bacillus-derived enzymatic hydrolysate of phycocyanin (using No. 2-1 "Alcalase 2.4 LFG"; Group A4), and sesame peptide (positive control; Group A5). The positive control sesame peptide was commercially available Sesame Peptide KM-20 (KISCO Corporation). 180 mg of the bulk powder of the test substance was weighed out and placed in a brown bottle, and 9 mL of water for injection was added and stirred thoroughly to prepare a 5 mL administration solution containing 100 mg.

[0096] (Test system) The experimental group, test substance, administration dose, administration volume, number of animals, and animal number are shown in Table 4 below. A single oral administration was performed using a disposable syringe and oral probe. The administration volume was calculated for each individual based on the body weight measured on the day of administration. Group A1 (water for injection) is also referred to as the vehicle group (negative control), and Group A5 (sesame peptide) is also referred to as the positive control group.

[0097]

[0098] (Weight Measurement) Body weight was measured on the day after arrival, on the day of grouping, and on the day of administration.

[0099] (Blood Pressure Measurement) The rats' blood pressure was measured using a non-invasive automatic sphygmomanometer ("BP-98A-L" (trade name), Softron Co., Ltd.) by the tail cuff method, including systolic blood pressure (SBP), mean blood pressure (MBP), and diastolic blood pressure (DBP). Blood pressure measurements were performed three times for each individual, and the average of the three measurements was calculated for SBP, MBP, and DBP. Each measurement value was expressed as the mean ± standard error for each group. Two-group tests were performed between Group A1 and Groups A2 to A5. For the two-group tests, Student's t-test was used when homogeneity of variance was confirmed by the F-test, and Aspin-Welch's t-test was used when homogeneity of variance was not confirmed. Statistical analysis was performed using "Stat Light" (registered trademark) (Yukkums Co., Ltd.), with a significance level of P<0.01 or P<0.05.

[0100] (Measurement results) <Systolic blood pressure (maximum blood pressure)> Table 5 shows the systolic blood pressure of rats that received a single oral dose of the test substance. A significant decrease in systolic blood pressure was observed in the sesame peptide group 3 and 6 hours after administration compared to the vehicle group, and a similar decrease was also observed in the systolic blood pressure ratio (%). A significant decrease in systolic blood pressure was observed in groups A2 and A3 6 hours after administration compared to the vehicle group. A significant decrease in systolic blood pressure ratio (%) was observed in group A4 3 and 6 hours after administration compared to the vehicle group.

[0101]

[0102] <Mean Blood Pressure> The mean blood pressure of rats given a single oral dose of the test substance is shown in Table 6. No significant difference in mean blood pressure was observed in any of the test substance groups, including the positive control A5, compared to the vehicle group. Regarding the mean blood pressure ratio (%), a significant decrease was observed in the A4 group compared to the vehicle group 6 hours after administration.

[0103]

[0104] <Diastolic Blood Pressure (Diastolic Blood Pressure)> The diastolic blood pressure of rats given a single oral dose of the test substance is shown in Table 7. No significant differences were observed in the diastolic blood pressure and diastolic blood pressure ratio (%) between the test substance-administered groups, including the sesame peptide group (positive control), and the vehicle group.

[0105]

[0106] (Discussion) Groups A3, A4, and A5 all significantly reduced systolic blood pressure in spontaneously hypertensive rats, with a particularly pronounced effect observed 6 hours after administration. These results suggest that the phycocyanin enzymatic hydrolysate is effective in suppressing and lowering blood pressure.

Claims

1. A composition for suppressing elevated blood pressure, containing a protease-digested product of phycocyanin as an active ingredient.

2. The composition of claim 1, which inhibits angiotensin converting enzyme.

3. The composition according to claim 1 or 2, which is a food or beverage composition.

4. The composition according to claim 1 or 2, which is a pharmaceutical composition.

5. The composition according to claim 1 or 2, which is a feed composition.

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