JP2008050269A - Oral ingestion material - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To obtain a composition of natural raw material effective for treatment of hypertension and having no adverse effect in which γ-aminobutyric acid being a kind of an amino acid existing in the natural world is a material having a noticeable effect as antihypertensive agent and even a low γ-aminobutyric acid content, more enhances high hypotensive effect of γ-aminobutyric acid. <P>SOLUTION: The composition containing γ-aminobutyric acid is obtained by reacting by-product of refined rice wine brewing as a raw material with lactic acid bacterium. The raw material may comprise rice bran and/or glutamic acid or its salt. The composition exhibits a strong hypotensive effect more than a case of ingesting only γ-aminobutyric acid alone. When both the composition and an ACE (angiotensin converting enzyme) inhibitory peptide are used, even the amount of each component is small, it is found that a synergistic effect is obtained and a strong hypotensive effect is exhibited. <P>COPYRIGHT: (C)2008,JPO&INPIT

Description

  The present invention relates to a composition using a sake brewing by-product as a raw material, and particularly relates to a composition for preventing, treating and improving hypertension.

  Although high blood pressure is listed as one of lifestyle-related diseases, high blood pressure has no special subjective symptoms unless it has progressed to a certain extent. For this reason, high blood pressure is also called a silent killer, and the medical condition may secretly progress without any subjective symptoms, and may cause a number of complications. The blood vessel wall is inherently elastic, but long-term hypertension causes arteriosclerosis and causes cerebral hemorrhage, cerebral infarction, aortic aneurysm, myocardial infarction, fundus bleed, and the like. In addition, as the arterial sclerosis progresses, nephrosclerosis develops and the renal function decreases, leading to renal failure and uremia. In addition, a burden on the heart may cause cardiac hypertrophy or heart failure.

  The hypertension treatment guidelines of the Japanese Society for Hypertension are classified into optimal blood pressure, normal blood pressure, normal high blood pressure, and high blood pressure based on blood pressure, systolic blood pressure (highest blood pressure) 140 mmHg or higher, or diastolic blood pressure (lowest blood pressure). 90 mmHg or more is defined as hypertension. Blood pressure tends to increase with age, and as of 2005, it is said that there are 30 to 35 million hypertensive patients nationwide, of which about 7 million are being treated.

Although the number of hypertensive patients is very large, essential high blood pressure is not found in the current medical examination, and accounts for more than 90% of hypertension. The remaining 10% of hypertension is called secondary hypertension or symptomatic hypertension, and the cause of increasing blood pressure has been found. Secondary hypertension includes aortic constriction, renovascular hypertension, renal parenchymal hypertension, primary aldosteronism, Cushing syndrome, pheochromocytoma, aortitis syndrome, thyroid dysfunction, etc. It is effective to lower blood pressure.

On the other hand, essential hypertension is associated with genetic factors and environmental factors such as lifestyle habits, such as excessive salt intake, obesity, excessive drinking, smoking, mental stress, dysregulation of the autonomic nervous system, excessive physical body. There are labor and inappropriate intake of protein and lipid. These factors have complex effects that make it difficult to identify the factors that cause hypertension. Accordingly, there are currently few effective methods for treating essential hypertension other than lowering blood pressure with antihypertensive agents.

  As antihypertensive agents as therapeutic agents for hypertension, the following are currently mainly mentioned. Diuretics that lower blood pressure by excreting sodium and water in the body to reduce blood volume, β-blockers or α-blockers that are sympathetic nerve inhibitors that relieve heart and blood vessel tension and lower blood pressure, dilate blood vessels and increase blood pressure An angiotensin converting enzyme (ACE) inhibitor that lowers blood pressure by suppressing the production of a hormone that increases blood pressure by constricting blood vessels (angiotensin II), angiotensin-converting enzyme (ACE) inhibitor that lowers blood pressure Angiotensin II receptor antagonists that suppress blood pressure and lower blood pressure.

  However, there are contraindications for the administration of these antihypertensive drugs, for example, thiazide diuretics for gout, antialdosterone diuretics for renal failure and hyperkalemia, and beta blockers for bronchial asthma and chronic obstructive pulmonary Α blockers for orthostatic hypotension, calcium antagonists for congestive heart failure, ACE inhibitors for pregnancy, hyperkalemia and bilateral renal artery stenosis, angiotensin II receptor antagonists It is contraindicated for pregnancy, hyperkalemia and bilateral renal artery stenosis.

  Also, taking these antihypertensive agents may cause side effects. Hypokalemia, hyperuricemia, blood concentration, etc. for diuretics, induction of bronchial asthma, worsening of chronic obstructive pulmonary disease, bradycardia, peripheral circulatory disturbance, lipid metabolism abnormalities, etc. Calcium antagonists include flushing, headache, palpitation, upper and lower limb edema and constipation, ACE inhibitors include dry cough, angioedema, and decreased renal function, and angiotensin II receptor antagonists include angioedema and decreased renal function .

  By the way, in recent years, γ-aminobutyric acid (GABA), which is a kind of amino acid, has attracted attention as a natural antihypertensive material. γ-Aminobutyric acid is an inhibitory neurotransmitter that is produced in vivo from glutamic acid and exists mainly in the hippocampus, cerebellum, spinal cord and the like. It exists mainly in the central nervous system but is also known to exist in peripheral tissues. As a pharmacological action, a blood pressure lowering action is recognized together with a brain metabolism promoting action, a growth hormone secretion promoting action and the like. Although the mechanism of antihypertensive action of γ-aminobutyric acid has not been fully clarified, γ-aminobutyric acid suppresses the increase of peripheral sympathetic nerves and suppresses the secretion of noradrenaline, which has vasoconstrictive action, thereby reducing the antihypertensive action. It is thought to show.

  γ-aminobutyric acid is abundant in seed germs such as brown rice. In addition, among commercially available foods, they are contained in many foods such as a part of yogurt, alcoholic beverages such as sake, wine and beer, vinegar, pickles, kimchi and vegetable juice. In particular, the content of kimchi is large, and it is considered that γ-aminobutyric acid is produced by lactic acid bacteria in kimchi. γ-aminobutyric acid is a non-protein amino acid, and is produced by decarboxylation of glutamic acid by the action of glutamic acid decarboxylase (GAD) widely distributed in microorganisms. For this reason, in order to obtain expensive γ-aminobutyric acid, a method using inexpensive glutamic acid or a salt thereof as a raw material is effective. As a method for producing γ-aminobutyric acid at high yield, there is a report that γ-aminobutyric acid was produced at high yield when sodium glutamate was added to rice bran or germinated brown rice bran and fermented with lactic acid bacteria (Patent Document 1, Patent Document 2).

Thus, γ-aminobutyric acid, which is a kind of naturally occurring amino acid, is expected to be used as an antihypertensive agent in recent years. However, γ-aminobutyric acid has a problem that the antihypertensive action has a certain limit even if its dosage is increased to some extent.

Therefore, there is a report that the antihypertensive effect was increased by administering γ-aminobutyric acid and an ACE inhibitory peptide in combination (Patent Document 3). In Patent Document 3, a sardine-derived peptide or a fermented milk peptide is used as an ACE-inhibiting peptide, but there is a problem of taste, and it is adjusted using a yogurt flavor and administered to a hypertensive subject. The dose of γ-aminobutyric acid was 100 μg / kg, and the blood pressure drop was measured 8 hours after the administration. As a result of the combination with the ACE inhibitory peptide, a blood pressure drop of about 20 mmHg was observed.

As methods for obtaining ACE-inhibiting peptides, isolation from hydrolysates such as milk casein, soy protein, sardine protein, corn, wheat, ovalbumin, etc. has been reported. There is also a report that it was isolated (Patent Document 4).

In addition, there is also a report that the antihypertensive effect was increased by combining wheat young leaves and a γ-aminobutyric acid-containing substance (Patent Document 5). According to Patent Document 5, a synergistic antihypertensive effect is obtained by applying a γ-aminobutyric acid-enriched treatment to young wheat leaves and adding a filamentous fungus culture or germ that is a composition containing γ-aminobutyric acid thereto. It is said that was obtained. In the experimental system of Patent Document 5, 9-week-old spontaneously hypertensive rats are administered 8 weeks of fungal culture, rice germ, etc. as a composition containing barley young leaves and γ-aminobutyric acid in the diet for 1 week. The amount of γ-aminobutyric acid calculated from the amount of food intake is considered to be about 2 to 7 mg.

JP-A-11-56276 JP 2005-65691 A JP 2002-241305 A JP-A-5-279263 JP 2002-227 A

Thus, γ-aminobutyric acid, a kind of naturally occurring amino acid, is a material that has attracted attention as an antihypertensive agent, and even if the content of γ-aminobutyric acid is low, the antihypertensive effect of γ-aminobutyric acid is further increased. There is a need to provide a composition of natural ingredients that is highly effective in treating hypertension and has no side effects.

  Therefore, as a result of intensive studies, the present inventors have obtained a fermented composition containing γ-aminobutyric acid by adding lactic acid bacteria to the by-product produced during the sake brewing process, and further adding rice mash to the sake brewing by-product. And / or by adding lactic acid bacteria to a mixture of glutamic acid or a salt thereof, a fermented composition containing γ-aminobutyric acid can be obtained more efficiently, and the composition thus obtained has the same amount. The present inventors have found that it exhibits a blood pressure lowering action stronger than that when γ-aminobutyric acid is taken alone, and has resulted in an effective natural raw material composition by preventing, treating and improving hypertension.

Furthermore, those obtained by further adding an ACE inhibitory peptide to these fermentation compositions exhibit a synergistic blood pressure lowering effect and exhibit a stronger blood pressure lowering effect than when the fermentation composition alone or the ACE inhibitory peptide alone is ingested. I found.

  The present invention has been completed on the basis of the above findings, and hereinafter includes a composition having an antihypertensive effect, an agent for preventing / treating / ameliorating hypertension containing the composition as an active ingredient, and preventing the hypertension. Or it is related with providing the food / beverage products etc. which attached | subjected the display to be used in order to improve, and those manufacturing methods.

Item 1. A composition comprising γ-aminobutyric acid obtained by causing lactic acid bacteria to act on a by-product generated during a sake brewing process.
Item 2. Item 2. The composition according to Item 1, wherein the by-product produced in the sake brewing process is sake lees obtained by brewing liquefied sake.
Item 3. Item 3. The composition according to Item 1 or 2, further comprising rice bran.
Item 4. Furthermore, glutamic acid and / or its salt are added, The composition of any one of claim | item 1 -3 characterized by the above-mentioned.
Item 5. Item 5. The composition according to any one of Items 1 to 4, wherein the lactic acid bacterium is a lactic acid bacterium belonging to Lactobacillus brevis.
Item 6. Item 6. An agent for preventing, treating, or improving hypertension, comprising the composition according to any one of items 1 to 5 as an active ingredient.
Item 7. Food / beverage products which contain the composition of any one of claim | items 1-5, and attached | subjected the display to the effect of being used in order to prevent or improve a hypertension.
Item 8. Item 6. A composition comprising the composition according to any one of Items 1 to 5 and an ACE inhibitory peptide.
Item 9. Item 9. An agent for preventing, treating, or improving hypertension, comprising the composition according to item 8 as an active ingredient.
Item 10. Item 9. A food or drink containing the composition according to item 8 and labeled to indicate that it is used for preventing or improving hypertension.
Item 11. Item 9. The method according to any one of Items 1 to 5, and / or the method according to Item 8.

  Hereinafter, the present invention will be described in detail.

(1) Compositions made from sake brewing by-products

  The sake brewing by-product used in the present invention is not particularly limited as long as it is other than the sake obtained in the sake brewing process, and may be a liquid product or a solid product. For example, a sake lees can be mentioned as a liquid product. Moreover, as a solid product, sake lees that are the remaining insoluble residue obtained by separating sake from sake lees can be cited. Any separation method from sake can be used. Any kind of sake lees can be used, but the sake lees obtained by so-called liquefaction preparation (hereinafter referred to as liquefaction lees), which is a brewing method of sake characterized by using a liquefied liquid of raw rice as the rice. Is particularly preferable because it has a feature that it contains more proteins and peptides than ordinary sake lees. Moreover, what is necessary is just to perform the alcohol removal contained in a brewing by-product according to a conventional method.

In the present invention, brewing by-products can be used alone as raw materials, and by adding rice bran and / or glutamic acid or a salt thereof to the brewing by-products, γ-aminobutyric acid can be efficiently contained, resulting in a blood pressure lowering effect. Rise. A fermentation composition is obtained by allowing lactic acid bacteria to act on a composition obtained by mixing or mixing these raw materials. The mixing ratio of the composition is not particularly limited, but the amount of rice bran added to the brewing by-product is preferably 0 to 50% by weight, more preferably 2 to 20% by weight. The addition amount of glutamic acid or a salt thereof is preferably 0 to 30% by weight, more preferably 1 to 15% by weight. The moisture is not particularly limited as long as lactic acid bacteria can grow, but when the brewing by-product is sake lees, it is preferably 0.5 to 10 times, more preferably 1 to 5 times that of sake lees. Furthermore, glucose may be added for the growth of lactic acid bacteria. The amount of glucose added is preferably 0 to 10% by weight, more preferably 0.5 to 5% by weight. After adding these, it grind | pulverizes and suspends using a mixer or a grinder. Lactic acid bacteria that have been pre-cultured are added to this mixed composition, and the amount of lactic acid bacteria added is preferably 10 ⁵ to 10 ⁹ cells / ml, more preferably 10 ⁶ to 10 ⁸ cells in the mixed composition. / Ml is desirable. The fermentation temperature is preferably 15 to 45 ° C, more preferably 30 to 40 ° C. The fermentation time is preferably 16 to 72 hours, more preferably 20 to 50 hours.

In performing lactic acid bacteria fermentation, it is desirable to make the fermentation conditions aerobic in order to improve the aroma and taste of the fermentation composition obtained from the mixed composition. For example, by providing a plurality of small ventilation holes on the lid of the fermentation vessel, lactic acid bacteria fermentation can be performed under aerobic conditions, and as a result, a fermentation composition having a good aroma and excellent taste is obtained. .

The fermentation composition thus obtained is subjected to solid-liquid separation by a method such as centrifugation or filter filtration, and the fermentation liquid supernatant powder is obtained by using a method such as freeze-drying or spray-drying the liquid part. Alternatively, the fermented composition powder can also be obtained by using a method such as freeze-drying or spray-drying as it is without solid-liquid separation of the obtained fermented composition.

The fermentation composition supernatant powder or the fermentation composition powder thus obtained may be hereinafter referred to as a fermentation composition.

(2) Lactic acid bacteria used for lactic acid fermentation

The lactic acid bacteria used in the present invention are not particularly limited as long as they have the ability to produce γ-aminobutyric acid, and examples include those belonging to the genus Lactobacillus, Leuconostoc, Streptococcus, Pediococcus, and Bifidobacterium. . Preferably those belonging to the Lactobacillus genus Among them, as this example, Lactobacillus brevis, Lactobacillus bulgaricus, Lactobacillus delbrueckii, Lactobacillus leichmannii, Lactobacillus plantarum, Lactobacillus lactis, Lactobacillus helveticus, Lactobacillus acidophilus, Lactobacillus casei, and be given Lactobacillus fermentum, etc. it can. Among these, those belonging to Lactobacillus brevis are more preferable.

In addition, the inventors isolated dozens of lactic acid bacteria having high γ-aminobutyric acid producing ability from food. Using each of these lactic acid bacteria, a fermentation test of liquefied koji and a taste sensory test of the fermented liquefied koji were conducted. Among them, one strain of lactic acid bacteria having excellent fermenting power and excellent liquefaction after fermentation was selected. As a result of the identification test of the selected strain, this strain was identified as Lactobacillus brevis.

(3) Blood pressure drop test

  Spontaneously hypertensive rat (SHR) is an inbred strain established by selective mating from normotensive Wistar Kyoto rat (WKY) in Kyoto University School of Medicine, Department of Pathology. Develops hypertension. Rats that develop hereditary hypertension have been established all over the world, but only SHR can surely develop hypertension, and this animal model is most commonly used in the research of hypertension and the development of new drugs. Yes.

In the present invention, the above SHR was used in the evaluation of blood pressure reduction. SHR gradually develops hypertension from around 3 months of age, and causes the same symptoms and lesions as human essential hypertension. For this reason, the SHR used in the test is preferably 20 to 30 weeks after the onset of hypertension. After each sample was administered to this SHR, the blood pressure of the SHR was measured with the cuff pressure of the tail, and the blood pressure drop was evaluated.

(4) ACE inhibitory peptide

  The ACE inhibitory peptide used in the present invention was prepared as follows. An appropriate amount of water was added to sake lees, and protease was added thereto to decompose proteins in the sake lees, and the supernatant after centrifugation was concentrated and dried. The protease used for the degradation may be any of acidic protease, neutral protease, and alkaline protease. For example, coculase, samoyase, rennet, protease A “Amano” G, protease M “Amano” G, protease N “Amano” G, Commercially available food industry enzymes such as Neurase F3G, Papain W-40, Equinezyme G, Promeline F, Samoaase PC10F, Peptidase R, Thermolysin, Morsine F, Sumiteam AP, Neutase, Actinase AS can be widely used.

When the ACE inhibitory activity of the composition thus obtained was measured, the ACE inhibitory activity was observed. Therefore, this liquor protease degradation product was used as an ACE inhibitory peptide. In the present invention, this composition is hereinafter referred to as an ACE inhibitory peptide, but no further purification or the like is performed on this composition in the present invention.

(5) Antihypertensive and therapeutic agent comprising fermented composition as active ingredient

  The antihypertensive / therapeutic agent using the fermented composition of the present invention can be used as it is or a pharmaceutically acceptable carrier (excipient, extender, binder, disintegrant, lubricant, moisturizer, colorant, And a flavoring agent are included) to obtain a suitable preparation. Moreover, this formulation can be prepared as a pharmaceutical composition by mixing conventional additives and the like.

  The formulation form is not particularly limited. For example, this pharmaceutical composition is prepared in a form (tablet, pill, capsule, powder, granule, syrup or the like; oral injection, infusion, external preparation, And various preparation forms such as parenteral administration agents such as suppositories). Orally administered agents are easier to use because they place less burden on patients than parenterally administered agents.

  As the excipient, known ones can be widely used, for example, various sugars such as lactose, sucrose and glucose, various starches such as potato starch, wheat starch and corn starch, various celluloses such as crystalline cellulose, Examples include various inorganic salts such as anhydrous calcium hydrogen phosphate and calcium carbonate.

  As the binder, known ones can be widely used, and examples thereof include crystalline cellulose, pullulan, gum arabic, sodium alginate, polyvinyl pyrrolidone, macrogol and the like.

  As the disintegrant, known ones can be widely used, and examples thereof include carboxymethyl cellulose, carboxymethyl cellulose calcium, hydroxypropyl cellulose, hydroxypropyl starch, starch, sodium alginate and the like.

  Examples of the lubricant include magnesium stearate, talc, and hardened oil.

  Known humectants can be widely used, and examples thereof include coconut oil, olive oil, sesame oil, peanut oil, soybean phospholipid, glycerin, and sorbitol.

As the flavoring agent, commonly used ones such as commonly used sweeteners, acidulants, and fragrances can be widely used, such as sucrose, glucose, fructose, xylitol, sorbitol, mannitol, cinnamon oil, mint oil, menthol and the like. It is done.

(6) Food and beverage composition containing antihypertensive agent

  The agent for preventing and treating hypertension of the present invention can be used as a food additive. The food additive may contain carriers and additives such as sugars, starches, cellulose, magnesium stearate, and vegetable oil, in addition to the antihypertensive agent for hypertension of the present invention. The dosage form of the food additive is not particularly limited. For example, it may be a powder form, a granule form, or a liquid form.

  The composition of the present invention does not have a taste or smell that impairs the flavor of food. Therefore, the type of food is not particularly limited. For example, sweets such as candy, gum, cake, pie, cookies, crackers, jelly, chocolate, pudding, ice cream, potato chips, sheep candy, rice crackers, buns, Chinese buns; liquors, teas, coffees, sports drinks Beverages such as soft drinks, soups and milk drinks; dairy products such as yogurt, butter and cheese; kneaded products such as ham, sausage, strawberries and bamboo rings; sauces, dressings, mayonnaise, soy sauce, miso, vinegar, miso , Processed tomato products (ketchup, tomato paste, tomato puree), seasonings such as kala soup, sake lees, granule soup; regular prepared vegetables such as sprinkles, pickles, boiled boiled fish, salted kelp; side dishes; noodles, cooked rice Major staple foods.

  Moreover, since the powder composition of only the liquid part of the present invention has high water solubility, liquid foods such as beverages, liquid seasonings such as sauces, dressings, soy sauce, vinegar, miso are preferable, Alcoholic beverages, teas, coffees, sports drinks, and soft drinks are more preferred. Further, since it exhibits high water solubility even under low pH conditions, there is an advantage that it can be suitably used as an additive for liquid acidic foods such as mayonnaise and dressings. Moreover, the composition pulverized without solid-liquid separation can be used for seasonings such as sauces, dressings and mayonnaises of the above liquid foods that do not require transparency. Furthermore, in order to withstand high-temperature and high-pressure treatment, there is an advantage that foods to which the composition of the present invention has been added can be subjected to heat and pressure sterilization and can be subjected to a special production process such as retort treatment. In addition, the present composition is suitable as a food additive from the viewpoint that its safety has historically been confirmed since it is contained in the sake-making raw material.

  In addition to the above, the food composition of the present invention may contain various additives that are usually added to processed foods. Various additives conventionally used in the preparation of food compositions can be added and blended. Examples of additives include stabilizers, pH adjusters, sugars, sweeteners, fragrances, various vitamins, minerals, antioxidants, excipients, solubilizers, binders, lubricants, and suspensions. Examples include agents, wetting agents, film-forming substances, flavoring agents, flavoring agents, colorants, preservatives and the like.

  In addition, the food composition of the present invention can be suitably used as a dietary supplement for preventing or improving hypertension, that is, a supplement. In this case, the food composition only needs to contain components known as a supplement carrier in addition to the composition of the present invention. Examples of such carriers include sugars, starches, cellulose, magnesium stearate, and vegetable oils.

  Although the shape of a supplement is not specifically limited, For example, shapes, such as a tablet form, powder form, and granular form, are mentioned.

  EXAMPLES Hereinafter, although an Example is shown and this invention is demonstrated in detail, this invention is not limited to these Examples.

Production of Fermentation Composition High in γ-Aminobutyric Acid (1)

150 ml of water was added to a composition in which 0, 5, 10, 20% rice bran was added to 50 g of liquefied rice cake, heated at 100 ° C. for 10 minutes, and cooled to room temperature. This was inoculated with 1 ml of 10 ⁷ cells / ml of a pre-cultured isolated lactic acid bacterium Lactobacillus brevis and fermented with lactic acid at 36 ° C. for 70 hours. The centrifuged supernatant was subjected to amino acid analysis (L-8800 type high-speed amino acid analyzer manufactured by Hitachi High-Technologies Corporation), and the concentrations of glutamic acid (Glu) and γ-aminobutyric acid (GABA) were measured.

  The results are shown in Table 1. The concentration of γ-aminobutyric acid in the fermented composition to which rice bran was added as compared with the case where rice bran was not added was extremely high, and the conversion rate from glutamic acid to γ-aminobutyric acid was 0, 5, 10, 20 for rice bran. % Was 21, 88, 94, and 94%, respectively. From the above results, it was found that the production efficiency of γ-aminobutyric acid was drastically improved by adding rice bran.

  Furthermore, even when adding glutamic acid or a salt thereof to the raw material, a phenomenon in which the production efficiency of γ-aminobutyric acid was improved by adding rice bran was recognized, and a γ-aminobutyric acid-rich fermentation composition was obtained.

Production of fermented composition with high content of γ-aminobutyric acid (2)

300 g of liquefied rice bran, 15 g of rice bran, 15 g of sodium glutamate and 6 g of glucose were added, and 750 ml of water was further added and pulverized and suspended with a mixer. This was inoculated with 10 ml of 10 ⁷ cells / ml of the pre-cultured isolated lactic acid bacterium Lactobacillus brevis and fermented with lactic acid at 36 ° C. for 48 hours. At this time, a vent hole was provided in the lid of the fermentation vessel so that the fermentation would not be under anaerobic conditions. By making fermentation aerobic, it was possible to obtain a fermented product with good aroma and excellent taste. This was centrifuged at 3000 g for 15 minutes, and the supernatant was lyophilized to obtain about 50 g of powder. When the γ-aminobutyric acid content of this powder was measured, 20% of the total weight was γ-aminobutyric acid. Thus, the powder of the fermentation composition with high content of γ-aminobutyric acid was obtained.

SHR blood pressure drop test

  The sample solution was orally administered to rats and blood pressure was measured after several hours. The short-term decrease in blood pressure at this time was regarded as an immediate effect of the sample. Rats were males of SHR / Izm (Shimizu Experimental Materials), 22 to 24 weeks old, and samples were administered by oral gavage using a gastric sonde at a single dose of 10 ml per kg body weight. did. When the sample was solid, the sample was dissolved in water to prepare 10 ml of an aqueous solution. Blood pressure was measured twice immediately before sample administration and 6 hours after administration. UR-5000 (manufactured by Ueda Seisakusho) was used for blood pressure measurement, and three points of systolic blood pressure (SBP), median blood pressure (MBP), and diastolic blood pressure (DBP) were recorded. The number of individuals per group was 6 and the test was conducted. Statistical processing was t-tested, and p <0.05 was considered significant.

In the following examples, blood pressure was measured using this method, and the effect of lowering blood pressure was evaluated.

Antihypertensive action of fermented liquefied koji composition

  The antihypertensive effect of the fermented liquefied koji composition obtained in Example 1 was examined. The fermented liquefied koji composition 20 μg / kg was administered to a 22-week-old male SHR. Since this fermented liquefied koji contains 20% γ-aminobutyric acid, the dose of γ-aminobutyric acid is 4 μg / kg. Moreover, 10 ml of water was administered as a blank, and 20 μg / kg of commercially available γ-aminobutyric acid (purity 98%; manufactured by Wako Pure Chemical Industries, Ltd.) was administered as a control. Blood pressure was measured according to the method of Example 3 before and after each administration.

The results are shown in Table 2. There was little change in blood pressure before and after administration of blank water. In addition, no change was observed in blood pressure before and after administration by administration of 20 μg / kg of commercially available γ-aminobutyric acid. However, administration of the fermented liquefied koji composition according to the present invention showed a decrease in blood pressure with a significant difference (p <0.05) between SBP and MBP after administration. The fermented liquor composition of the present invention administered in this test has a γ-aminobutyric acid content of 4 μg / kg, which is 1/5 of the control commercial γ-aminobutyric acid administration group. The blood pressure lowering effect was observed only in the liquefied sputum composition administration group. From this, the fermented liquefied koji composition of the present invention has an action of lowering blood pressure in addition to the effect of γ-aminobutyric acid, and has a stronger blood pressure lowering action than when the same amount of γ-aminobutyric acid is administered. I understood.

Synergistic effect of fermented liquefied koji composition and ACE inhibitory peptide

  The blood pressure lowering effect of the fermented liquefied koji composition and the ACE-inhibiting peptide was examined by administering each of the rats alone or a combination thereof. As the ACE inhibitory peptide, the above-mentioned unpurified ACE inhibitory peptide-containing product derived from sake lees was used. Rats were 24 week old SHR males, and the administration method was the same as in Example 3. The administration groups were the following three groups. Administration group 1: fermented liquefied koji composition of the present invention 10 μg / kg, administration group 2: ACE inhibitory peptide 10 mg / kg, administered group 3: fermented liquefied koji composition of the present invention 5 μg / kg + ACE inhibitory peptide 5 mg / kg. The blood pressure before and after administration was measured according to the method of Example 3, and the change in blood pressure before and after administration in each administration group and the difference in blood pressure between administration groups after administration were examined.

  First, Table 3 shows the results of changes in blood pressure before and after administration in each administration group. As a result, when the fermented liquefied koji composition of the present invention alone (10 μg / kg) in administration group 1 was observed, blood pressure decreased in all of SBP, MBP, and DBP, but in Example 4, it was observed at the time of administration of 20 μg / kg. As a result, no significant difference was observed. Even in the administration group 2 with ACE inhibitory peptide alone (10 mg / kg), some blood pressure decrease was observed with SBP, but almost no blood pressure decrease was observed with MBP and DBP. On the other hand, in the combined administration of the fermented liquefied koji composition of the present invention and ACE inhibitory peptide (fermented liquefied koji 5 μg / kg, ACE inhibitory peptide 5 mg / kg) of administration group 3, the blood pressure of all of SBP, MBP and DBP In particular, SBP and MBP showed a blood pressure decrease with a significant difference of p <0.01. Moreover, the blood pressure lowering value of SBP in administration group 3 was 27 mmHg, which was the largest among the three groups.

Then, the blood pressure after administration of each administration group is shown in Table 4. Administration group 1 and administration group 3, administration group 2 and administration group 3 were compared. As a result, the blood pressure after administration was lower in the administration group 3 than in the administration group 1, and in the administration group 3 was lower in both SBP and MBP than in the administration group 2. In particular, in SBP, a significant difference of p <0.05 was observed in comparison between administration groups 1 and 3, and a significant difference of p <0.01 was observed in comparison between administration group 2 and administration group 3. From this, in the group where the fermented liquefied koji composition of the present invention and the ACE inhibitory peptide were used in combination, the blood pressure lowering effect superior to both the fermented liquefied koji composition alone and the ACE inhibitory peptide alone was observed, and the present invention. It was found that when the ACE inhibitory peptide was further used in combination with the fermented liquefied koji composition, a synergistic blood pressure lowering effect was obtained.

Claims (11)

A composition comprising γ-aminobutyric acid obtained by causing lactic acid bacteria to act on a by-product generated during a sake brewing process. The composition according to claim 1, wherein the by-product generated in the sake brewing process is sake lees obtained by brewing liquefaction-added sake. Furthermore, the rice bran is mix | blended, The composition of Claim 1 or 2 characterized by the above-mentioned. Furthermore, glutamic acid and / or its salt are added, The composition of any one of Claims 1-3 characterized by the above-mentioned. The composition according to any one of claims 1 to 4, wherein the lactic acid bacterium is a lactic acid bacterium belonging to Lactobacillus brevis. An agent for preventing, treating, or improving hypertension, comprising the composition according to any one of claims 1 to 5 as an active ingredient. Food / beverage products which contain the composition of any one of Claims 1-5, and were attached | subjected with the display to be used in order to prevent or improve a hypertension. A composition comprising the composition according to any one of claims 1 to 5 and an ACE inhibitory peptide. An agent for preventing, treating or improving hypertension, comprising the composition according to claim 8 as an active ingredient. A food / beverage product comprising the composition according to claim 8 and having a display indicating that the composition is used for preventing or improving hypertension. The manufacturing method of the composition of any one of Claims 1-5, and / or the composition of Claim 8.