JP5749469B2 - Antihypertensive - Google Patents

Description

  The present invention relates to a composition having a blood pressure lowering effect and use thereof.

  In recent years, due to changes in lifestyle habits, the number of people with lifestyle-related diseases has increased, which has become a major social problem. Hypertension (symptom) is one of the diseases having a high incidence among lifestyle-related diseases. High blood pressure is known to cause various complications such as cerebral hemorrhage, subarachnoid hemorrhage, cerebral infarction, myocardial infarction, angina pectoris, nephrosclerosis and the like. In addition, hypertension sometimes presents severe symptoms due to the combination with obesity, hyperlipidemia, and diabetes, and effective treatment thereof is strongly desired.

  Known antihypertensive substances include diuretics, calcium antagonists, angiotensin I converting enzyme (ACE) inhibitors, angiotensin II receptor antagonists, beta blockers, etc., and many natural products and chemical compounds have been reported. Yes. In view of easy administration, there is a demand for substances that are effective for oral administration and have a safer blood pressure lowering effect.

  Patent Document 1 discloses that a fermented product obtained by subjecting fish meat such as hockey and cod or fish meat-derived protein to lactic acid fermentation using lactic acid bacteria has an action of inhibiting the activity of angiotensin converting enzyme.

  Funazushi is a type of ripe sushi and is a local dish in Shiga Prefecture. Sushi sushi is made by salting fresh crucian fish for several months, then pickled with cooked rice, and fermenting naturally in the sushi for half a year to a year. Rice (rice of sushi sushi (good)) is generated. Most of the sushi sushi rice is discarded after the sushi sushi is produced, and the reuse of the sushi is also desired from the viewpoint of resource reuse and environmental issues. However, it has not yet been reported that rice of sushi has physiological effects such as blood pressure lowering effects.

JP 2008-133251 A

  An object of the present invention is to provide a blood pressure lowering agent which is safe without side effects and exhibits an antihypertensive effect by oral administration or ingestion and its use. Another object of the present invention is to provide a method for effectively using waste.

  As a result of intensive studies in view of the above situation, the present inventors have found that an extract of fermented rice (rice from sushi), which is a byproduct of sushi, has high ACE inhibitory activity. The inventors have also found that a water extract is particularly suitable as a rice sushi extract. As a result of further research, it was found from experiments using spontaneously hypertensive rats (SHR) that an excellent blood pressure-lowering effect can be obtained when the rice extract of sushi is orally administered.

Sushi sushi is a fermented food that has been eaten in the area around Lake Biwa as a special product of Shiga Prefecture, and it has been reported that it is healthier than before, but it has an excellent blood pressure lowering for rice extract, a by-product of sushi. The fact that it has an action was a finding first found by the present inventors. Rice for sushi sushi is fermented rice made from cooked rice, rice cake, and salt, and is a safe and highly effective material that has no side effects even when ingested for a long time as a daily ingested food. For this reason, the rice of sushi and its extract are expected to be used for foods for specified health use, functional foods, animal feeds, etc. for the purpose of lowering blood pressure. Currently, most of the sushi sushi rice is discarded after the sushi sushi is manufactured, but by using it as a blood pressure lowering agent, the waste can be used effectively and the burden on the environment can be reduced.
The present inventors have further studied based on these findings, and have completed the present invention.
That is, the present invention includes the following inventions.

Item 1. An antihypertensive agent characterized by containing rice from sushi or an extract thereof.
Item 2. Item 2. The blood pressure lowering agent according to item 1, comprising an extract of rice from sushi.
Item 3. Item 3. The blood pressure lowering agent according to Item 1 or 2, wherein the extract of rice from the sushi is a water extract of rice from the sushi.
Item 4. Any of paragraphs 1 to 3, wherein the sushi sushi rice or an extract thereof is orally administered at a dose of 1 to 20 mg / kg per body weight as a protein contained in the sushi sushi rice or an extract thereof per day. The blood pressure lowering agent according to one item.
Item 5. Item 5. An agent for preventing or treating hypertension, comprising the blood pressure lowering agent according to any one of Items 1 to 4.
Item 6. Item 5. A food or drink composition for preventing or treating hypertension, comprising the antihypertensive agent according to any one of Items 1 to 4.
Item 7. Item 5. A feed for preventing or treating hypertension, comprising the antihypertensive agent according to any one of items 1 to 4.

  The antihypertensive agent of the present invention is highly safe, has no side effects even when administered or ingested for a long period of time, and exhibits an effective antihypertensive action, so that it has the effect of safely and effectively improving hypertension. In addition, by adding the antihypertensive agent of the present invention to foods and drinks and feeds, food and drinks and feeds such as nutritional supplements suitable for the purpose of lowering blood pressure, foods for specified health use, functional foods, etc. It can be easily manufactured. Furthermore, according to this invention, the rice of the sushi which has been mainly discarded until now as a by-product in the manufacture of the sushi can be used effectively. For this reason, waste can be reduced, the burden on the environment can be reduced, and the cost of disposal can be reduced.

FIG. 1 is a photograph of rice cake of sushi (A), water extract of rice of sushi (B), and residue (C) after extraction of rice of sushi. FIG. 2 is a diagram showing the results of examining the protein elution amount from rice of sushi with different extraction solvents. FIG. 3 is a diagram showing the ACE inhibitory activity of rice sushi extract from different types of extraction solvents. FIG. 4 is a diagram comparing the ACE inhibitory activity of rice sushi extract from different ripening periods. FIG. 5 is a view showing changes in blood pressure when a rice extract of sushi is administered once to SHR. FIG. 6 is a diagram showing changes in blood pressure when the rice extract of sushi is administered continuously to SHR for 10 days. FIG. 7 is a diagram showing the results of examining the relationship between the dose of the rice extract (converted to protein) and the change in blood pressure when the rice extract of salmon sushi is administered once to SHR.

The antihypertensive agent of the present invention contains sushi rice or an extract thereof.
Rice for sushi is fermented with rice pickled with crucian sushi when making sushi. Rice of sushi can be obtained by manufacturing sushi.

  Sushi sushi can usually be produced using crucian, salt and rice (rice cooked rice) as raw materials by a method conventionally performed around Lake Biwa in Shiga Prefecture, Japan. As described later, the preferred rice for sushi in the present invention is produced using crucian, rice (rice), salt and miso as raw materials.

  As the raw material for the sushi, it is sufficient to use a carp of the carp family, Carassius subfamily, Carassius buergeri grandoculis; 1), giant beech (Carassius buergeri buergeri), common beech (Carassius cuvieri), nagabuna (Carassius buergeri subsp. 2), and European beech (Carassius carassius). In this invention, the sushi using these 1 type (s) or 2 or more types can be used. Of these, rice with sushi made using Nigorobuna is preferred because of its high ACE inhibitory activity and high blood pressure lowering action. Nigorobuna is an endemic species of Lake Biwa. The funa may be male or female.

  Manufacture of sushi is usually performed by performing a salt cutting process and a main pickling (rice pickling) process in this order. Below, the manufacturing method of sushi is demonstrated.

(Salt cutting)
First, remove the gills and scales from the crucian carp, remove the internal organs other than the ovaries from the gills, and wash well. Fill the abdominal cavity with salt. Sprinkle salt around the crucian fish, soak them in salted rice cakes, drop the lid, place the weight, and store in a cool dark place (salthouse). This is called “salt cutting”. The amount of salt at the time of salt cutting can be adjusted as appropriate, but it is generally used in the same amount as that of the funa. The salt cutting (salt storage) period is usually about 1 to 30 months. Preferably, it is about 3 to 15 months.

(Japanese pickles)
Next, the salted crucible is taken out and salted out. Salt removal can be usually performed by washing with water or soaking. It is preferable to carry out the salt removal to such an extent that a little salty taste remains. Then, it is preferable to dry the salt-free crucian carp. Drying is usually performed by sun drying (usually about 1 to 3 hours) or (night) shade drying (usually about 10 to 15 hours).
Next, the rice mixed with the salt is stuffed into the dried laver and / or the belly of the dried crucian carp so that it is pickled. The amount of salt is preferably about 2% to 3% with respect to the mass of cooked rice. In pickling rice, it is preferable to work with miso on the hand as appropriate in order to prevent rice from sticking to the hand and to produce sushi with an excellent blood pressure lowering effect. Thus, the rice of the sushi sushi manufactured by using a crucible, rice (rice cooked rice), salt, and miso as a raw material is used suitably as rice of the sushi sushi in this invention.

  Usually, this rice pickle is also done in a bowl, and not only the crucian fish but also the rice is spread alternately, and the crucian meat is spread between the inside and outside of the body (fish meat). Pickle in this state, drop the lid, put the weight and start the fermentation. After the start of fermentation, if it is summer, it is preferable to store the salmon soaked with crucian carp in a cool and dark place. And fermentation is performed as it is. The fermentation (ripening) period is usually about 2 months or longer, but preferably about 5 to 30 months, more preferably about 5 to 24 months, and further preferably about 12 to 24 months. In this case, not only cooked rice but also koji, liquor, etc. may be mixed and pickled if desired. Rice of sushi sushi fermented with crucible for about 2 months or more, preferably about 5 to 30 months, more preferably about 5 to 24 months, more preferably about 12 to 24 months is a preferred embodiment of the present invention. One.

  Fermented rice (boiled sushi rice) separated from boiled sushi (boiled potato) after being pickled is used as an active ingredient in the present invention. The rice of the sushi may have the shape of a rice grain or a paste. Since it may be difficult to completely separate the sushi and rice, the rice of the sushi used in the present invention may be mixed with the contents of the crucian sushi used in its production. . Preferably, the sushi sushi is preferably 10% by mass or less based on the sushi sushi. More preferably, substantially only the sushi sushi is used.

  In this invention, the rice of the sushi produced in this way can be used conveniently. In addition, commercially available salmon sushi is usually filled with fermented rice (meal of salmon sushi) around or in the belly. In this invention, the rice of the sushi used for such a commercially available sushi can also be used suitably. Rice of sushi sushi made from the above-mentioned crucian, rice (rice cooked rice), salt and miso is commercially available from Kimura Suisan Co., Ltd. together with sushi.

  In the present invention, sushi rice can be used as an active ingredient of an antihypertensive agent as it is, but as long as the effect of the present invention is exhibited, a dried product obtained by drying sushi rice, the rice (or its dried product) Can be used as the rice for sushi. The rice of sushi can be used as it is as the antihypertensive agent of the present invention, but as described later, an appropriate amount of additional components may be added to form a composition.

  As an active ingredient in the present invention, rice sushi extract is suitable. The sushi rice extract is produced by adding a solvent to the above-described sushi rice to extract soluble components. In the present invention, rice from sushi may be used as it is as an extraction raw material, but what has been subjected to pretreatment such as drying and pulverization may be used as an extraction raw material. That is, the rice sushi rice extract is produced by performing a step (extraction step) of extracting the sushi rice, or a dried product, a pulverized product or a ground product thereof with a solvent.

  The solvent for extraction is not particularly limited, but an aqueous solvent is preferable. In other words, the sushi rice extract of the present invention is preferably an aqueous solvent extract of sushi rice. Use of an aqueous solvent is preferable because an extract having an excellent blood pressure lowering effect can be obtained. Further, the aqueous solvent is preferably used from the viewpoints of convenience of extraction work, safety because it is an aqueous solvent extract, and safety when the solvent remains. . As the aqueous solvent, water or a mixed solvent of water and an organic solvent is preferable. Specific examples include water; lower alcohols such as methanol, ethanol, isopropanol, and t-butyl alcohol; and mixed solvents of water and lower alcohols. In the case of using a lower alcohol, it is preferable to use methanol and ethanol from the viewpoint of solvent removal (refer to Japanese Patent Application Laid-Open No. 08-164303 for techniques for removing lower alcohols such as methanol and ethanol). The mixing ratio of water and organic solvent in the mixed solvent can be set as appropriate. Among these, water, ethanol, or a mixed solvent of water and ethanol is preferable, and water is particularly preferable. When water is used as the extraction solvent, an extract exhibiting a particularly excellent blood pressure lowering effect can be obtained. The water extract of rice cake of sushi is one of the most preferred embodiments of the extract in the present invention.

  The amount of the solvent used is preferably about 1 to 25 times, more preferably about 1 to 20 times, and more preferably about 1 to 10 times the mass of the rice, unless the rice of sushi sushi, which is the extraction material, is dried. Is more preferable. If the rice of the sushi is dried, about 2 to 40 times the dry substance amount of the rice is preferable, and about 2 to 20 times is more preferable.

  The extraction temperature is preferably such that the starch does not elute from the rice of the sushi. For example, the extraction is preferably performed at about -3 to 10 ° C. The extraction temperature is more preferably about 0 to 10 ° C, more preferably about 0 to 5 ° C, particularly preferably about 0 to 2 ° C, and most preferably about 0 ° C. The extraction time may be appropriately selected depending on the extraction temperature, and is not particularly limited. For example, when extraction is performed at about −3 to 10 ° C. using an aqueous solvent, the extraction is preferably performed for about 10 minutes or more. 10 minutes to 24 hours are more preferable. In order to suppress the dissolution of starch, the extraction time is more preferably about 10 to 30 minutes, and further preferably about 10 to 20 minutes. In addition, the extraction may be left standing or stirred.

  The particularly preferred extract of the present invention is a sushi rice with water and an extraction temperature of about −3 to 10 ° C. (preferably about 0 to 10 ° C., more preferably about 0 to 5 ° C., more preferably about 0 to 0 ° C. 2 ° C., particularly preferably about 0 ° C.) for about 10 to 20 minutes. It is preferable to stir during extraction.

  The processing after the extraction can be performed according to a conventional method. For example, an extract can be obtained by eluting soluble components in the extraction step and then removing solids. The removal of the solid substance can be performed by a commonly performed method, for example, centrifugation or filtration. If desired, the removed solid can be washed with the solvent used for extraction and combined with the filtrate (extract). What is necessary is just to distill away a solvent by pressure reduction or a heating as needed for the obtained extract. However, excessive heating is not preferred, and it is preferably concentrated under reduced pressure at room temperature to about 50 ° C.

  The obtained extract can be used as an active ingredient of the antihypertensive agent of the present invention as it is in the extracted solution, but as long as the effects of the present invention are exerted, desalting treatment such as dialysis, ion exchange resin treatment, etc. Or may be subjected to further purification treatment. Moreover, you may perform processes, such as concentration, dilution, and filtration, as needed. Preferably, desalting is performed. Since the extract of rice cake of sushi may have a high salt content as it is, an extract exhibiting a superior blood pressure lowering action can be obtained by desalting. Further, the extracted solution may be subjected to treatment such as concentration to dryness, spray drying, freeze drying, etc., and used as a dried product.

That is, the extract of rice cake of sushi in the present invention includes an extract obtained using rice of sushi sushi as an extraction raw material, a desalted solution of the extract, a diluted solution or a concentrated solution of the extract or the desalted solution. A crude product or purified product of the extract or desalted solution thereof, a dried product obtained by drying the extract or desalted solution thereof, a crude product or purified product of the extract or desalted solution thereof, Any dried product obtained by drying is included.
The extract thus obtained can be used as it is as the antihypertensive agent of the present invention. However, as described later, an appropriate amount of additional components may be added to form a composition.

  The sushi rice and its extract have an excellent ACE inhibitory activity and have a blood pressure lowering action, so a composition for lowering blood pressure, such as food and drink, health food, functional food, pharmaceutical composition, etc. Used as an active ingredient. In the case of a medicine, it can be a parenteral dosage form or an oral dosage form, but is suitable for oral administration and is preferably an oral dosage form (internal use).

  The composition containing rice cake of sushi or its extract is preferably a solid preparation such as a tablet, capsule, chewable agent, film agent, powder, pill, granule or the like. These preparations can be easily produced by using the sushi sushi rice or its extract as it is, or by mixing various additives as desired, and using a well-known conventional preparation method. Additives are not particularly limited, and known ones can be used. For example, excipients (eg, lactose, starch, crystalline cellulose, dextrin, glucomannan, etc.), binders (eg, starch, gelatin, carme) Sodium, methylcellulose, hydroxypropylmethylcellulose, hydroxypropylcellulose, polyvinylpyrrolidone, etc.), disintegrating agents (eg, starch, carmellose sodium, etc.), lubricants (eg, talc, magnesium stearate, calcium stearate, etc.), antioxidants ( For example, nitrite, ascorbic acid, cysteine, etc.), coloring agents (eg, tar pigment, licorice extract, etc.), preservatives (eg, paraoxybenzoates, benzalkonium chloride, chlorobutanol, etc.), coating agents (eg, , Mud hydroxypropyl cellulose, hydroxypropyl methylcellulose, hydroxypropyl methylcellulose phthalate, hydroxypropyl methylcellulose acetate succinate, ethyl cellulose, cellulose acetate phthalate, etc.), a plasticizer (e.g., glycerin, etc.) and the like. If necessary, it can be used in combination with other drugs.

  The content of the sushi sushi rice or the extract thereof in the preparation is usually about 0.000001 to 99% by mass in the final preparation.

The amount of the sushi sushi rice or the extract thereof is not particularly limited as long as the effects of the present invention are exhibited. For example, the sushi sushi rice or the extract thereof per day, The protein contained in the extract may be orally administered at a dose of usually about 1 mg / kg or more per body weight (in terms of protein), and is preferably orally administered at a dose of about 1 to 20 mg / kg. . More preferably, per day, the protein contained in the sushi sushi rice or extract thereof is about 3 to 15 mg / kg, more preferably about 5 to 15 mg / kg, and particularly preferably about 5 to 10 mg / kg. Is administered orally. This amount may be taken once or divided into 2-3 times.
The amount of protein in the rice sushi extract can be measured by a known method such as the Lowry method. The amount of protein in the sushi sushi rice can be determined from the measurement value obtained by measuring the amount of protein in the sushi sushi rice extract.

  The antihypertensive agent of the present invention has excellent ACE inhibitory activity. The antihypertensive agent of the present invention has few side effects and exhibits an excellent antihypertensive effect by oral administration. Therefore, the antihypertensive agent is suitably used as a medicament for preventing or treating hypertension. An agent for preventing or treating hypertension containing the antihypertensive agent is also one aspect of the present invention. The dosage form, usage method, and the like of a prophylactic or therapeutic agent for hypertension are the same as those of the above-described antihypertensive agent. “Prevention” includes suppressing or delaying the onset. “Treatment” includes not only the complete cure of a symptom or disease, but also the amelioration or alleviation of the symptom.

  The antihypertensive agent of the present invention can be used as the above-mentioned pharmaceuticals, and is a functional food for the purpose of lowering blood pressure, the purpose of improving hypertension or the purpose of preventing hypertension, food and drink such as food for specified health use or drink Can be used. The food or drink composition for preventing or treating hypertension containing the antihypertensive agent of the present invention is also one aspect of the present invention. The amount of sushi rice or its extract contained in the food / beverage product composition can usually be determined by appropriately selecting from the range of about 0.000001 to 99% by mass in the final composition.

  The antihypertensive agent of the present invention is also suitably used as a food additive or the like. A food additive containing rice from sushi or an extract thereof can be suitably used to enhance the blood pressure lowering action of food and drink. For example, when the antihypertensive agent of the present invention is added to a food or drink, the blood pressure lowering action of the food or drink can be enhanced as compared with the case where the agent is not added. Enhancing the blood pressure lowering action of a food or drink includes giving the blood pressure lowering action to a food or drink that does not originally have a blood pressure lowering action.

  The food / beverage composition containing the antihypertensive agent of the present invention is produced by blending the rice of sushi or the extract thereof, or the rice of sushi or the extract-containing preparation at the time of producing the food / beverage product.

  When the antihypertensive agent of the present invention is used as a food or drink composition, the form is not particularly limited. Moreover, food-drinks compositions can also be made into processing forms, such as a natural liquid food, a semi-digested nutrient food, a component nutrient food, or a drink agent. Furthermore, the food-drinks composition concerning this invention is good also as an easily soluble formulation added to an alcoholic beverage or mineral water at the time of use. More specifically, the food / beverage composition according to the present invention includes, for example, confectionery such as biscuits, cookies, cakes, Japanese confectionery; bread, noodles, cooked rice or processed products thereof; fermented foods such as sake, medicinal liquor; yogurt, It can be in the form of livestock farm foods such as ham, bacon, sausage and mayonnaise; beverages such as fruit juice drinks, soft drinks, sports drinks and alcoholic drinks.

  As one of the preferred embodiments in the present invention, the rice cake of sushi or the extract thereof, or the rice product of the sushi or the extract-containing preparation thereof is added to the ripened sushi (for example, sprinkled on the rice sushi). Is mentioned. Thereby, the blood pressure lowering effect of the sushi can be enhanced while maintaining the flavor of the sushi.

  In addition, the food / beverage composition according to the present invention, for example, under the control of a dietitian based on a doctor's meal, adds the food / beverage composition of the present invention to any food at the time of cooking in a hospital meal, It can also be given to patients in the form of food prepared in The food / beverage composition of the present invention may be liquid or solid such as powder or granule.

  The food-drinks composition which concerns on this invention may contain the auxiliary component conventionally used in the foodstuff field | area. Examples of the auxiliary component include lactose, sucrose, liquid sugar, honey, magnesium stearate, oxypropylcellulose, various vitamins, trace elements, citric acid, malic acid, fragrance, and inorganic salt.

  The amount of intake of the food and beverage composition according to the present invention varies depending on the mammal's symptoms, age, sex, etc., so it cannot be said unconditionally. It is preferable to take the same amount as in the case of the agent.

  Although it does not specifically limit as a subject which ingests or administers the antihypertensive agent of this invention, the prevention or treatment agent of hypertension, the food-drinks composition for prevention or treatment of hypertension, It is possible to develop an animal with high blood pressure or develop hypertension Sexual animals are particularly preferred. The animal is preferably a human.

  The antihypertensive agent of the present invention can also be used to lower the blood pressure of animals other than humans. For example, a composition containing rice from sushi or an extract thereof can be used as animal feed or animal medicine. A feed for preventing or treating hypertension containing the antihypertensive agent is also one aspect of the present invention.

  The veterinary medicine can be prepared by a known preparation method by appropriately mixing the above-described excipients or the like with rice of sushi or its extract as necessary. A feed for preventing or treating hypertension containing an antihypertensive agent is produced by blending rice from sushi or an extract thereof, or the rice containing sushi or an extract-containing preparation thereof at the time of animal feed production.

  The animal is not particularly limited as long as it is a useful animal, and examples thereof include mammals such as dogs, cats, monkeys, rats, mice, cows, pigs and horses, birds such as chickens, and fish. Of these, mammals are preferred. The intake of rice cake of sushi or its extract is not particularly limited, and can be set as appropriate according to the type of animal.

  EXAMPLES Hereinafter, although an Example is given and this invention is demonstrated concretely, this invention is not limited to these Examples at all.

Example 1
(Changes in components and angiotensin I converting enzyme inhibitory activity before and after desalting)
As the rice for the sushi, fermented rice stuffed around and around the sushi commercially available from Kimura Suisan Co., Ltd. was used. Kimura Suisan's crab sushi is a crab sushi that has been pickled for 2 years using crucian, rice, salt and miso as raw materials.

  Extraction from fermented rice was carried out based on a working hypothesis that a water / ethanol system under cooling would be appropriate in order to efficiently elute functional components without eluting starch as much as possible.

1. Extraction method 1) 1000 mL of water was added to 1000 g of fermented rice (untreated).
2) The sample obtained in 1) was extracted by stirring with a stirrer at a water temperature of 0 ° C. for 10 minutes.
3) The fermented rice suspension obtained in 2) was centrifuged (15,400 × G, 10 minutes, 0 ° C.).
4) The supernatant was filtered using filter paper (Toyo Roshi Kaisha, No. 2).
5) The filtrate was allowed to stand and then centrifuged (15,400 × G, 10 minutes, 0 ° C.).
6) The obtained supernatant was used in the following experiment as an extract (fermented rice sample 1, before desalting).

The appearance of the fermented rice before extraction, the water (100%) extract of fermented rice extracted by the above method, and the appearance of the residue are shown in FIG. From the left of FIG. 1, there are A fermented rice (untreated), B fermented rice water (100%) extract, and C fermented rice water (100%) after-extract residue.
The pre-extraction fermented rice (FIG. 1A) had a considerable amount of rice grains and was yellowish. In the residue after extraction (FIG. 1C), the rice grains became slightly finer, and the color became whitish than before extraction. The water extract of fermented rice (FIG. 1B) was slightly cloudy but was a highly transparent solution.

2. Desalination method 850 mL of the obtained extract (fermented rice sample 1, before desalting) was electrodialyzed assylator G3 (trade name, Asahi Kasei Co., Ltd.) and Neoceptor cartridge AC-110-400 (trade name, Astom Corp.) Was used to obtain a desalted extract (fermented rice sample 1, after desalting).

3. Angiotensin I converting enzyme inhibitory activity measured desalted extract (fermented rice sample 1 was desalted) for, in accordance with Ito et al. Method ^*, it was measured of angiotensin I converting enzyme (ACE) inhibitory activity. The value was expressed as IC50 (ACE 50% inhibitory concentration).
* The method of Ito et al. Is described in K. Itou and Y. Akahane, Fisheries Science, vol. 70, 1121-1129 (2004).

The ACE inhibition activity (ACE inhibition rate) (%) was calculated by the following formula.
ACE inhibitory activity (%) = 100 x (CS) / (CB)
C: Value of ultraviolet absorption 228nm of control (distilled water) (OD228)
S: UV absorption value of sample 228nm (OD228)
B: Value of blank UV absorption 228nm (OD228)

  The pH was measured with a Horiba pH meter (model number TOA HM-30V, manufactured by HORIBA, Ltd.). Salinity was measured with a simple salinometer (Horiba Compact Salinometer Model No. C-121 CARDY SALT, manufactured by HORIBA, Ltd.). The protein concentration was measured using the standard substance as bovine serum albumin by the Lowry method.

4). Result The result regarding fermented rice sample 1 (before desalting and after desalting) is shown in Table 1.

Desalination with the electrodialyzer acylator G3 was very good. Since there were few impurities etc. affecting the desalting treatment, the salt concentration and the liquid amount of this time were reduced to a salt concentration appropriate for a physiological activity measurement sample by a short time treatment (about 8 hours).
The ACE 50% inhibitory concentration (IC50: inhibitor concentration to inhibit 50% of enzyme activity) of the fermented rice extract (fermented rice sample 1, before desalting) was 0.079 mg / mL in terms of protein amount by the Lowry method. It was. Although the ACE inhibitory activity of the extract after desalting (fermented rice sample 1, after desalting) was slightly reduced, these ACE inhibitory activities were sufficiently high. Although the pH of the water extract was as low as 4.5, there was concern about the effect on the measurement system, but there was no effect on the measurement system.

Example 2
(Examination of functional component extraction method)
In Example 1, a considerable amount of Lowry reaction positive substance (protein) could be confirmed in the extract with water (100%) under cooling. Further, the aqueous extract showed high ACE inhibitory activity.
Furthermore, in order to obtain an efficient extraction method, the difference by the extraction solvent which changed the water / ethanol mixing ratio was examined. In the same manner as in Example 1, fermented rice stuffed around and around the rice cake sushi commercially available from Kimura Suisan Co., Ltd. was used as rice for the rice cake sushi.

  As shown in Table 2, the amounts of extraction solvent and fermented rice used are shown in Table 2 using water (sample No. 1) or a mixture of water and ethanol (sample No. 2-5) as the extraction solvent. Except for the above, 1. The fermented rice was extracted in the same manner as above to obtain an extract. The mixing ratio of water and ethanol shown in Table 2 is a volume ratio.

Table 2 and FIG. 2 show protein elution amounts (protein concentration (mg / mL) in each extract) depending on the extraction solvent.
In Table 2 and FIG. 3, the ACE inhibitory activity (IC50, protein concentration (mg / mL) conversion amount) of the extract obtained using each extraction solvent is shown. 2 and 3, W / E represents a volume mixing ratio of water (W) and ethanol (E).

The IC50 for ACE inhibitory activity indicates the concentration at which the activity is inhibited to 50%. Therefore, the lower the value, the higher the inhibitory activity. There was no difference in the elution degree of the Lowry method positive substance (protein) depending on the extraction solvent (Table 2 and FIG. 2). In addition, the ACE inhibitory activity was highest when extracted with 100% water (Table 2 and FIG. 3).
For comparison, cooked rice (not fermented) was treated as in Example 1. In the same manner as above, the rice extract was obtained by stirring and extracting with a 100% solvent at 0 ° C. and a stirrer. This cooked rice extract showed no ACE inhibitory activity.

  Therefore, in Examples 1 and 2, the simplest extraction method of “extracting fermented rice without treatment and using water (100%) as an extraction solvent while stirring under cooling” is the most efficient ACE inhibitory activity. The substance could be extracted. This extraction method does not require a special reagent, is a simple operation, and is an effective method for obtaining a sample for measuring ACE inhibitory activity.

Reference example 1
Natto (commercial product, trade name Hokkaido small soybean natto, manufactured by Azuma Foods Co., Ltd.) was freeze-dried.
Ten times the amount of distilled water was added to freeze-dried natto, and the mixture was stirred and extracted with a stirrer for 2 hours. Thereafter, the mixture was centrifuged (20000 × g, 2 ° C., 10 minutes), and the supernatant was used as a sample solution for measurement. The ACE inhibitory activity was measured using ACE Kit-WST (trade name, manufactured by Dojindo).
The ACE inhibitory activity value of the natto extract was 0.11 mg / mL (converted to protein concentration). In addition, the ACE inhibitory activity value of the rice bran extract measured by the same method was 0.028 mg / mL (protein concentration conversion).

Reference example 2
The ACE inhibitory activity IC50 value of the mackerel extract of mackerel was 0.10 mg / mL (converted to protein concentration). This value is according to “Yoshiaki Akabane, Mitsufumi Ito; Journal of Japanese Society of Taste and Smell, Vol. 14, 117-128, 2007”. This method for measuring ACE inhibitory activity is the same as in Example 1. In addition, the ACE inhibitory activity value of the rice bran extract measured by the same method was 0.03 mg / mL (protein concentration conversion).

Example 3
(ACE inhibitory action of rice cakes with different production sites and aging periods)
In Reference Examples 1 and 2, the rice bran extract showed a higher ACE inhibitory activity than mackerel duck and natto, indicating that it has the effect of suppressing an increase in blood pressure. Therefore, the ACE inhibitory activity of rice cakes with different production sites and different aging periods was examined.

1. Method Four types of sushi sushi rice water extracts with different aging (rice pickles) periods (about 2 to 24 months) were used as samples.

Extraction was performed as described in Example 1 of Example 1 except that four types of sushi rice with different aging periods (about 2 to 24 months) were used as fermented rice. It was performed in the same manner as the above method. The following four types of extracts were obtained and used as Sample A (1), Sample A (2), Sample B, and Sample C, respectively.
Sample A (1): Sushi sushi rice water extract using sushi sushi rice (manufactured by “Sumimi” Co., Ltd.) produced by aging for about 2 months Sample A (2): Aged for about 5 months鮒 Sushi rice water extract sample B using sushi sushi rice (manufactured by “Shomi” Co., Ltd) Ｃ Sushi rice water extract sample C: 鮒 Sushi rice water extract solution using sushi rice (manufactured by Kimura Suisan Co., Ltd.) produced by aging for about 24 months

  The protein concentration of the extract was measured by DC Protein Assay Kit (trade name, manufactured by Bio Rad), and bovine serum albumin was used as a standard substance. Unlike the methods of Examples 1 and 2, the ACE inhibition rate was measured using ACE Kit-WST (trade name, manufactured by Dojin Chemical Co., Ltd.). The amount of sample corresponding to an inhibition rate of 50% (value converted to protein concentration) IC50 was expressed as ACE inhibitory activity. The salinity concentration and pH were measured by the same method as in Example 1.

2. Results The results are shown in Table 3 and FIG. From these results, it was found that rice of sushi with an aging period of about 2 months or more shows high ACE inhibitory activity.

Example 4
(Administrative effect 1 on spontaneously hypertensive rats (SHR))
1. Method 1) Breeding of SHR A group of six 7-week-old male spontaneously hypertensive rats (SHR) obtained from Japan SLC (Hamamatsu City) was used for a 2-week preliminary breeding. After preliminary breeding, individuals with systolic blood pressure (maximum blood pressure) exceeding 180 mmHg were selected and used for subsequent experiments. SHR is raised in a constant environment of temperature 23 ± 2 ° C, humidity 55 ± 5%, light / dark cycle 12 hours (light period 8-20 o'clock), artificial feed (CE-2; Nippon Claire), and sterilized tap water Was ad libitum.

2) Administration experiment Administration was by gavage using a stainless steel sonde, and the dose was 1 mL per 100 g body weight of SHR measured immediately before. For the administration sample (boiled sushi rice extract), a water dilution of sample C (an extract using fermented rice manufactured by Kimura Suisan Co., Ltd.) prepared in Example 3 with the protein concentration adjusted to 1.0 mg / mL. Was used. The dose of the sample was 10 mg / SHR body weight 1 kg as protein (in terms of protein). Further, the salt concentration of this administration sample was 0.88%. As a control sample, saline having the same salt concentration was used. For comparison, a cooked rice extract obtained by extracting unfermented cooked rice by the method described in Example 1 was administered. The dose of cooked rice extract was 10 mg / SHR body weight of 1 kg as protein.
In a single administration, the animals were fasted from 24 hours before administration to 8 hours after administration, but the food was freely fed for 10 consecutive days. In the experiment of continuous administration for 10 days, the amount of the sushi rice extract or the control sample was administered once a day for 10 consecutive days.

3) Measurement of blood pressure After fixing SHR to the chamber and warming it at 37 ° C for 15 minutes, the blood pressure was measured at systolic blood pressure at the base of the tail using a non-invasive blood pressure meter (model number MK-1030; Muromachi Kikai). Was measured at least 5 times per animal and the average of 6 animals was determined. In a single administration experiment, blood pressure was measured immediately before administration (0 hour) and every 2 hours after administration up to 8 hours. In continuous administration for 10 days, blood pressure was measured immediately before administration (day 0), 1, 4, 7, and 10 days after administration, and 5 days after administration was discontinued. In continuous administration, the sushi rice extract was forcibly orally administered once a day immediately after blood pressure measurement by the above method.

2. Results FIG. 5 shows the results of a single-dose experiment, and FIG. 6 shows the results of a 10-day continuous administration experiment. In FIG. 5, ◯ is a control (control to which 0.88% saline was administered) group, ▲ is a group to which rice extract is administered, and ■ is a group to which sushi rice extract is administered. is there. All were administered at a dose of 10 mg / kg per body weight in terms of protein. In FIG. 6, ◯ is a control group (administered with 0.88% saline), and ■ is a group administered with salmon sushi rice extract.
* In FIG.5 and FIG.6 has shown that there exists a significant difference (P <0.01) compared with a control group as a result of comparing the average value of each group in each measurement time. In FIG. 5, one-way analysis of variance was used, and in FIG. 6, t-test was used. # Indicates that there is a significant difference (P <0.01) compared to the blood pressure immediately before administration (0 hour or 0 day). The t-test was used in both FIGS.

  In a single administration of the sushi rice extract, blood pressure decreased from 2 hours to 6 hours after administration, and a significant difference was observed between the control group and the cooked rice extract group (FIG. 5). ). Moreover, when the sushi sushi rice extract was administered continuously for 10 days, the blood pressure gradually decreased, and the blood pressure decreased after 7 days was maintained, and returned to the original state 5 days after the administration was discontinued (FIG. 6). In the control group, there was no significant decrease in blood pressure after administration in either single administration or continuous administration. Therefore, the reduction in blood pressure of SHR caused by the administration of sushi sushi rice extract was due to the extract components of sushi sushi rice. I found out. The sushi sushi rice extract showed a blood pressure lowering action on SHR, and it was expected that the action could be sustained by continuous administration.

Example 5
(Administrative effect 2 on spontaneously hypertensive rats (SHR) 2)
Next, a single dose experiment was conducted in which the dose of the sushi sushi rice extract was 10 mg, 5 mg, and 1 mg, respectively, in terms of protein per kg body weight of the rat. In the same manner as in Example 4, an aqueous diluted solution of Sample C (an extract using fermented rice manufactured by Kimura Suisan Co., Ltd.) prepared in Example 3 in which the protein concentration was adjusted to 1.0 mg / mL was administered to the administration sample (鮒Used as sushi rice extract). The experimental method is the same as the single-dose experiment of Example 4 except that the dose was changed.

  The results are shown in FIG. In FIG. 7, □ is a group (5 mg / kg administration group) administered with sushi sushi rice extract as a protein (5 mg / kg administration group), and ■ is a group (10 mg / kg administration with sushi sushi rice extract as a protein). / Kg administration group) and ● are groups (1 mg / kg administration group) administered with 1 mg / kg of sushi rice extract as protein. A circle represents a control group to which a control sample (0.88% saline) was administered. As a result, the blood pressure decreasing tendency was hardly different between the case where 5 mg / kg of the sample C water dilution (sushi sushi rice extract) was administered as protein and the case where 10 mg / kg was administered.

  As shown in FIG. 7, when 1 mg / kg of persimmon sushi rice extract per day as a protein was ingested as protein, the blood pressure of SDR decreased compared to before intake. When 5 mg / kg or 10 mg / kg of persimmon sushi rice extract was ingested as protein per day, a blood pressure lowering action superior to that ingested 1 mg / kg of protein was obtained. Furthermore, since the blood pressure lowering tendency hardly changed between 5 mg / kg administration of sushi sushi rice extract as a protein and 10 mg / kg administration, the effect of suppressing blood pressure elevation on SHR Is considered to be sufficiently expected at a dose of 5 mg / kg as protein per day per body weight (in terms of protein).

Although an example of the formulation example of the blood pressure lowering agent of this invention is shown below, this invention is not limited to these.
Sample C produced in Example 3 was lyophilized. The freeze-dried product obtained from 1 mL of this fermented rice sample was 105 mg.

1. Manufacture of tablets 1050 mg of dry powder (containing 49 mg of protein) obtained by drying 10 mL of sample C prepared in Composition Example 3 in 1 tablet
Lactose 100mg
Magnesium stearate 2mg
After mixing the above-mentioned components, the tablet is produced by a conventional tablet production method to produce a tablet.

2. Preparation of capsule 1 Composition in capsule 1 1050 mg of dry powder obtained by drying 10 mL of sample C prepared in Example 3 (containing 49 mg of protein)
Corn starch 100mg
Lactose 100mg
Magnesium stearate 2mg
After the above components are mixed, the capsules are manufactured by filling gelatin capsules by a conventional capsule manufacturing method.

Claims (5)

  An antihypertensive agent comprising a water extract of rice from a sushi.   The blood pressure according to claim 1, wherein the water extract of rice cake of sushi is orally administered at a dosage of 1 to 20 mg / kg per body weight as protein contained in the water extract of rice of sushi per day. Depressant.   A prophylactic or therapeutic agent for hypertension comprising the antihypertensive agent according to any one of claims 1 and 2. Prophylactic or therapeutic drink food composition of hypertension containing antihypertensive agent according to any one of claims 1 or 2.   A feed for preventing or treating hypertension, comprising the antihypertensive agent according to any one of claims 1 and 2.