JP2022042716A - Agent for lowering extracellular moisture ratio - Google Patents

Abstract

To provide an agent for lowering an extracellular moisture ratio.SOLUTION: An agent for lowering an extracellular moisture ratio contains at least one selected from the group consisting of euglena, paramylon, processed paramylon, and β-1,3-glucan.SELECTED DRAWING: None

Description

The present invention relates to an extracellular water ratio inhibitor and the like.

Edema (swelling) is a condition that is seen on a daily basis and is caused by various causes such as aging, inflammation, disease, and external stimuli. Edema, if left untreated, can lead to tissue fibrosis, skin keratinization, and limited range of motion. In addition, it can be a factor that lowers the QOL (Quality Of Life), mainly for external reasons.

Edema can be regarded as a state in which excess water is accumulated in the tissue gap, and the extracellular water ratio is obtained by dividing the extracellular water content by the body water content (extracellular water content + intracellular water content). appear. That is, a high extracellular water ratio means that it is edema, or that it is close to or can cause edema.

Euglena is a microalgae belonging to the genus Euglena (= genus Euglena) and is used as a food material. In addition, Euglena extract has also been applied to the skin (Patent Document 1).

Special Table 2008-526954 Gazette

An object of the present invention is to provide an extracellular water ratio inhibitor.

As a result of diligent research in view of the above problems, the present inventor contains at least one selected from the group consisting of Euglena, paramylon, paramylon processed product, and β-1,3-glucan, and suppresses the extracellular water ratio. If it is an agent, it has been found that the above problem can be solved. As a result of further research based on this finding, the present invention was completed. That is, the present invention includes the following aspects.

Item 1. An extracellular water ratio inhibitor containing at least one selected from the group consisting of euglena, paramylon, processed paramylon, and β-1,3-glucan.
Item 2. Item 2. The extracellular water ratio inhibitor according to Item 1, which contains at least one selected from the group consisting of euglena, paramylon, and processed paramylon.
Item 3. Item 2. The extracellular water ratio inhibitor according to Item 1 or 2, which contains the Euglena and the Euglena is Euglena gracilis.
Item 4. Item 2. The extracellular water ratio inhibitor according to Item 1 or 2, which contains the Euglena and the Euglena is the Euglena gracilis EOD-1 strain (accession number FERM BP-11530).
Item 5. Item 4. The extracellular water ratio inhibitor according to any one of Items 1 to 4, which is used for preventing or ameliorating edema.
Item 6. The edema is edema caused by decreased function of cell membrane, edema caused by impaired blood flow or decreased metabolism, age-related edema, renal edema, cardiac edema, hepatic edema, endocrine edema, nutritionally impaired edema. Item 5. The extracellular water ratio inhibitor according to Item 5, which is at least one selected from the group consisting of drug-induced edema, idiopathic edema, venous edema, lymphatic edema, inflammatory edema, and vascular edema. ..
Item 7. Item 5. The extracellular water ratio inhibitor according to Item 5 or 6, wherein the edema includes edema in the upper body.
Item 8. Item 6. The extracellular water ratio inhibitor according to any one of Items 1 to 7, which is a food composition, a dietary supplement, a food additive, or a pharmaceutical.
Item 9. Item 6. The extracellular water ratio inhibitor according to any one of Items 1 to 8, which is an oral composition.
Item 10. An agent for preventing or ameliorating edema, which comprises at least one selected from the group consisting of euglena, paramylon, processed paramylon, and β-1,3-glucan.

According to the present invention, it is possible to provide an extracellular water ratio inhibitor, and further to provide a preventive or ameliorating agent for edema.

The measurement result of the extracellular water ratio of the trunk is shown (Test Example 1). The vertical axis shows the relative value of the extracellular water ratio of the trunk. In the horizontal axis, 0W indicates the measurement start date (before the start of ingestion), 4W indicates the measurement result 4 weeks after the start of the test, and 8W indicates the measurement result 8 weeks after the start of the test. The measurement result of the extracellular water ratio of the right arm is shown (Test Example 1). The vertical axis and the horizontal axis are the same as those in FIG. * Indicates that p <0.1 (significant).

In the present specification, the expressions "contains" and "contains" include the concepts of "contains", "contains", "substantially consists" and "consists of only".

The present invention, in one aspect thereof, comprises an extracellular water ratio inhibitor or prevention of edema, which comprises at least one selected from the group consisting of Euglena, paramylon, paramylon processed product, and β-1,3-glucan. It relates to an improving agent (in the present specification, it may be referred to as "the agent of the present invention"). This will be described below.

1. 1. Euglena Euglena is a microalgae belonging to the genus Euglena (= genus Euglena), and is not particularly limited as long as it is. As Euglena, specifically, for example, Euglena gracilis , Euglena longa , Euglena caudata , Euglena oxyuris , Euglena tripteris , Euglena proxima , Euglena viridis , Euglena sociabilis , Euglena ehrenbergii , Euglena Euglena acus , Euglena geniculata , Euglena intermedia , Euglena mutabilis , Euglena sanguinea , Euglena stellata , Euglena terricola , Euglena klebsi , Euglena rubra , Euglena cyclopicola and the like. Among these, Euglena gracilis is preferably mentioned from the viewpoint that the effect of the present invention can be more reliably exerted, and more preferably Euglena gracilis EOD-1 strain [Product Evaluation by Incorporated Administrative Agency on June 28, 2013]. Technology Infrastructure Organization Patent Organism Depositary Center {NITE-IPOD (Postal code 292-0818, 2-5-8 Kazusakamatari, Kisarazu City, Chiba Prefecture, Japan, Room 120)} under the provisions of the Budapest Treaty, as the accession number FERM BP-11530 International deposit].

The morphology of Euglena is not particularly limited as long as it contains most of Euglena's cell body or its components. Examples of the form of Euglena include a dry powder form of Euglena, a suspension of Euglena, a Euglena extract and the like, and among them, a dry powder form of Euglena is preferable.

The paramylon content of Euglena in a dry state is, for example, 50% or more, preferably 60% or more, and more preferably 70% or more.

Euglena may be a single species or a combination of two or more species.

2. If β-1,3-glucan and paramylon β-1,3-glucan have one sugar chain (or sugar chain structure) in which glucose is linked only by β1,3 bonds as the main chain. There are no particular restrictions. β-1,3-glucan is not limited to linear ones, but also includes those having branched chains.

The weight average molecular weight of the β-1,3-glucan derivative is not particularly limited, but is, for example, 1 × 10 ⁴ to 2 × 10 ⁶ , preferably 5 × 10 ⁴ to 1 × 10 ⁶ , and more preferably 1 × 10 ⁵ to. There are 1 x 10 ⁶ . The weight average molecular weight can be measured by the GPC method.

The β-1,3-glucan may be obtained by chemical synthesis, but from the viewpoint of availability and the like, natural β-1,3-glucan produced by various organisms is preferable. Examples of the natural β-1,3-glucan include paramylon, curdlan, laminarin, callose, lentinan, schizophyllan and the like. Among these, paramylon is preferably mentioned. Hereinafter, paramylon will be described.

Paramylon is a β-1,3-glucan derived from Euglena and is not particularly limited as long as it is.

The Euglena from which paramylon is derived is the same as the explanation in "1. Euglena" above.

The mass average molecular weight of paramylon is not particularly limited, but is, for example, 1 × 10 ⁴ to 5 × 10 ⁶ , preferably 2 × 10 ⁴ to 1 × 10 ⁶ , more preferably 5 × 10 ⁴ to 1 × 10 ⁶ , still more preferable. Is 1 × 10 ⁵ to 5 × 10 ⁵ .

The mass average molecular weight can be measured by SEC-MALS analysis under the following conditions:
Detector: Multi-angle scattering detector (DAWN HELEOS II manufactured by Wyatt Technology)
Differential refractometer detector (Optilab T-rEX manufactured by Wyatt Technology)
Column used: 2 TSKgel α-M (manufactured by Tosoh)
Mobile phase: 0.05M potassium bromide added DMSO
Flow rate: 0.5 mL / min.

Paramylon exists in Euglena cells as paramylon particles in which triple helical structures formed by β-1,3-glucan chains are usually highly integrated under a certain regularity.

The shape of the paramylon particles is not particularly limited, but is usually a flat spheroid.

The particle size distribution of the paramylon particles is not particularly limited, but is, for example, 0.5 to 15 μm, preferably 1 to 6 μm. The average particle size of the paramylon particles is also not particularly limited, but is, for example, 1 to 10, preferably 2 to 4 μm.

The form of paramylon is not particularly limited as long as it contains paramylon. Examples of the form of Euglena include a dry powder form of paramylon, a suspension of paramylon, and the like, and among them, a dry powder form of paramylon is preferable.

Paramylon may be used alone or in combination of two or more.

3. 3. Method for Producing Euglena and Paramylon Euglena can be prepared in large quantities by a method including a step of culturing Euglena contained in a liquid (culture step). The culturing step can be performed, for example, according to a known method (for example, the method described in Japanese Patent No. 5883532). In the culturing step, Euglena microalgae are typically cultivated under aerobic conditions while stirring a liquid (culture solution) containing water, Euglena, and nutrients available to Euglena.

Nutrients include sugars (monosaccharides such as glucose (dextrose) and fructose (fruit sugar)) and minerals (eg sodium, potassium, magnesium, calcium, iron, zinc, molybdenum, copper, phosphorus, nitrogen, sulfur, or boron. Vitamin Bs (eg, vitamin B1 (thiamine), vitamin B2 (riboflavin), niacin, pantothenic acid, vitamin B6 (pyridoxine, pyridoxal, or pyridoxamine), vitamin B12 (cyanocobalamine), folic acid, biotin, etc.) Be done. The concentration of nutrients in the culture solution is not particularly limited as long as Euglena can survive, proliferate, and the like.

The light conditions of the culturing step are not particularly limited, and the culturing step may be carried out under either light or dark conditions. When culturing in heterotrophic culture, it is cultivated under dark conditions. As a bright condition, normal light intensity for growing algae can be adopted. Dark conditions include, for example, less than 10 μmol / m ² / s, preferably complete dark conditions with no light.

The culture temperature in the culture step is not particularly limited as long as it is a temperature at which Euglena can grow. As the culture temperature (temperature of the culture solution), for example, 20 ° C to 35 ° C is adopted.

The pH of the liquid in the culturing step is not particularly limited as long as it is a pH at which Euglena can grow. For example, 3.0 to 5.5 is adopted as the pH at which Euglena can grow.

After the culturing step, it is preferable to concentrate Euglena by centrifugation or gravity separation of the liquid. The resulting Euglena can be subjected to additional treatments (eg, suspension in liquid, dispersion in water or oil, extract extraction, dry powdering, etc.), depending on the desired form.

Paramylon particles can be produced by separation, isolation, or purification from Euglena according to or according to known methods (eg, the method described in Japanese Patent No. 5883532). Paramylon particles can be easily obtained, for example, by recovering the cell content component obtained by destroying the cell membrane of Euglena. In addition, paramylon particles may be purified as needed. Various types of purification of paramylon particles are known (for example, Japanese Patent No. 5883532), and these methods can be used. Examples of the purification step include a surfactant treatment step and a cleaning step. The resulting Euglena can be subjected to additional treatments (eg, suspension in liquid, dispersion in water or oil, dry powdering, etc.), depending on the desired form.

Four. Paramylon processed product The paramylon processed product is obtained by processing paramylon, for example, physical treatment, chemical treatment, or the like, and is not particularly limited as long as it is. Examples of the processed paramylon product include fibrous paramylon and amorphous paramylon. Amorphal paramylon can be obtained by chemically treating according to or in accordance with a known method, for example, using the method described in JP-A-2011-184592.

As the processed paramylon product, fibrous paramylon is preferable. The fibrous paramylon will be described below.

The fibrous paramylon is a β-1,3-glucan derived from Euglena and is not particularly limited as long as it is in a fibrous form. Amorphous paramylon obtained by chemically treating paramylon particles (alkali treatment, etc.) has been reported so far, but this is not recognized as fibrosis when observed with an electron microscope, and its shape and size are Since it is an amorphous mass, it is not included in fibrous paramylon.

The weight average molecular weight of the fibrous paramylon is not particularly limited, but is, for example, 1 × 10 ⁴ to 2 × 10 ⁷ , preferably 1 × 10 ⁵ to 5 × 10 ⁵ .

The weight average molecular weight can be measured by the following method by SEC-MALS analysis: SEC device: LC-10ADvp system (Shimadzu Co., Japan), column used: KD-806M (shodex., Japan). ,
MALS detector: DAWN HELEOSII (wyatt Technologies., USA), eluent: 1% LiCl / DMI,
Flow rate: 0.5 mL / min.

The diameter of the fiber of the fibrous paramylon is not particularly limited, but is, for example, 10 to 500 nm, preferably 20 to 300 nm, and more preferably 50 to 200 nm. The diameter of the fibers of the fibrous paramylon can usually be measured based on the electron micrograph of the fibrous paramylon.

The settling volume of the fibrous paramylon in water is not particularly limited, but is, for example, 30 to 300 mL / g, preferably 50 to 250 mL / g, and more preferably 70 to 200 mL / g.

The submerged volume can be measured according to or according to the following method:
Measure according to the method described in "Supervised by the Japanese Society of Dietary Fiber, edited by the Editorial Board of the Japanese Society of Dietary Fiber (2008) Dietary Fiber-Basics and Applications-Third Edition, p.111 First Publishing, Tokyo". .. Specifically, it is as follows. Weigh 125 mg of the sample slurry-like test sample into a 25 mL volume plastic tube in terms of dry mass, and shake the plastic tube vigorously by hand to stir the contents. Then transfer the contents to a graduated cylinder with a volume of 25 mL and add pure water until it reaches 25 mL. After stirring the liquid in the measuring cylinder, let it stand at 37 ° C for 24 hours. This causes the sample to precipitate, resulting in two layers separated across the interface: a layer predominantly containing the precipitated sample (lower layer) and a layer predominantly containing water (upper layer). The volume of the lower layer is obtained from the scale of the measuring cylinder, and the obtained volume is divided by the sample mass (dry mass) to calculate the submerged volume (mL / g). The test is performed 3 or 4 times and the mean and standard deviation are calculated.

Fibrotic paramylon has a relatively high resistance to enzymatic degradation. For example, the amount of monomer (glucose) produced by the decomposition of β-glucanase is, for example, 0.1 to 50 mg, preferably 1 to 10 mg per 1 g of fibrous paramylon.

This amount can be measured according to or according to the following method:
Reaction solution [Test substance 30 mg (dry weight), buffer solution (Tokyo Kasei Kogyo Co., Ltd. B0156, potassium hydrogen phthalate-sodium hydroxide buffer (pH 4.0)) 5 mL, enzyme solution (Nippon Biocon Co., Ltd. endo- 1,3-β-Glucanase (enzyme content: 50 units / mL)) 0.1 mL, pure water, reaction solution volume 10 mL] is prepared and shaken horizontally at 40 ° C for 24 hours at 45 rpm. Immediately after shaking, freeze and store and lyophilize for concentration. After lyophilization, add 0.5 mL of pure water to each sample and stir (concentrate 20 times). Centrifuge (10000G, 5 minutes, 4 ° C) and repeat the work of collecting the supernatant twice. The glucose concentration in the recovered supernatant is measured using a measurement kit (Glucose CII-Test Wako, manufactured by Wako Pure Chemical Industries, Ltd.). Based on the measured values, the amount of glucose produced per 1 g of the test substance (mg) is calculated.

Fibrotic paramylon has relatively low solubility in alkaline solutions. For example, fibrous paramylon is insoluble in 0.1-0.3 M aqueous sodium hydroxide solution. Here, "insoluble" means that, for example, the absorbance (660 nm) of the solution after suspending the fibrous paramylon in the aqueous solution (for example, immediately after 1 hour has elapsed) is, for example, 0.1 or more, preferably 1.0. It means that it is the above.

Solubility can be measured according to or according to the following method:
Suspend 250 mg (dry weight) of the test substance in 10 mL of the test solution (pure water, 0.1 M NaOH aqueous solution, 0.3 M NaOH aqueous solution) in the vial. After shaking the vial vigorously by hand for 20 seconds and shaking at 80 rpm for 1 hour in a shaker, measure the absorbance of the liquid in the vial at 660 nm, respectively. The absorbance is measured using a spectrophotometer V-730 manufactured by JASCO Corporation.

The relative value of the crystallinity of the fibrous paramylon with respect to the granular paramylon (crystallinity of the fibrous paramylon / crystallinity of the granular paramylon) is, for example, 0.60 to 0.90, preferably 0.65 to 0.80.

Crystallinity can be measured according to or according to the following method:
XRD measurement is performed on the test substance. The conditions are as follows. Equipment: PANalytical X'Pert3 Powder, tube voltage: 45kV, tube current: 40mA, measurement range: 5.005 to 50.018 °, measurement interval: 0.013 °, analysis software: High Score. The crystallinity is analyzed by the ratio of the strength of the amorphous part to the strength of the crystalline part at 2θ = 5 to 80 °. The analysis is performed after removing the background from each measurement device (background setting Auto, venting factor 0, granularity 100), and the amorphous part is determined by the tangent line passing through 2θ = 14, 29 °. do. The pending factor and granularity conditions that determine each amorphous part are 0/20.

The fibrous paramylon may be in a form dispersed in a solvent such as water, or may be in a dry form. The fibrous paramylon can be redispersed in water, even in dry form.

In addition, in this specification, a "dry form" means a water content of 15% by mass or less, preferably 10% by mass or less, more preferably 5% by mass or less.

As the fibrous paramylon, preferably, a defibrated product of paramylon particles obtained by physically defibrating the paramylon particles can be used. Further, the euglena defibrated product obtained by applying this defibration treatment to Euglena can also be used as a fibrous paramylon.

The defibration treatment hardly cleaves the hydrogen bonds of β-1,3 glucan present in the paramylon particles (for example, 10% or less, 5% or less, 2% or less of the hydrogen bonds of β-1,3 glucan). A process that can be defibrated (without cutting less than 1%), or unraveling some or all of the β-1,3-glucan chains present in the paramylon particles or the triple spiral structure they form. There are no particular restrictions as long as the processing can be performed. It is preferable to defibrate the β-1,3 glucan present in the paramylon particles with almost no breakage to form a fibrous form. A known treatment capable of grinding (shearing) or crushing (preferably grinding (shearing)) fine particles such as paramylon particles can be adopted as the defibration treatment.

The defibration treatment can be performed using a device such as a known grinder (shearing machine) or crusher. Examples of the apparatus used for the defibration treatment include a stone mill type grinder, a jet mill, a twin-screw kneader, a high-pressure homogenizer, a high-pressure emulsifier, a twin-screw extruder, and a bead mill. Among these, a stone mill type grinder and a bead mill are preferable.

The defibration treatment can be performed by a wet method or a dry method. Wet defibration treatment is preferable because it enables more efficient dispersion of fibrous paramylon in the solution. The solvent used in a wet manner is not particularly limited as long as it is a solvent in which fibrous paramylon can be dispersed, and water can be preferably used.

The defibration treatment may be performed by one type alone or in combination of two or more types. Further, the paramylon may be partially defibrated, which is the intention of the present invention as long as the defibrated paramylon is contained.

Five. Use At least one selected from the group consisting of Euglena, paramylon, paramylon processed product, and β-1,3-glucan (hereinafter, may be referred to as "active ingredient of the present invention") has an extracellular water ratio. It has an inhibitory effect and a preventive or ameliorating effect on edema. Therefore, the active ingredient of the present invention can be used for suppressing the extracellular water ratio and / or for preventing or ameliorating edema.

In addition, "suppression" includes not only decreasing but also suppressing an increase in what is on an increasing trend (decreasing or not increasing the amount of increase). Further, "improvement" means improvement or alleviation of symptom or condition, prevention or delay of deterioration of symptom or condition, reversal, prevention or delay of progression of symptom or condition.

The extracellular water content ratio is a value obtained by dividing the extracellular water content by the body water content (extracellular water content + intracellular water content), and can be measured according to a known method. For example, it can be measured by a bioelectrical impedance analysis method.

Edema is not particularly limited and includes various types of edema. Edema includes, for example, edema caused by decreased function of cell membrane, edema caused by impaired blood flow or decreased metabolism, age-related edema, renal edema (eg, caused by acute glomerular nephritis, nephrosis syndrome, etc.). , Cardiac edema (eg caused by congestive heart failure, etc.), Liver edema (eg caused by liver cirrhosis, etc.), Endocrine edema (eg, caused by hypothyroidism / hyperactivity, etc.), Nutritional disorders Edema (eg, due to protein-losing gastroenteropathy, etc.), drug-induced edema (eg, due to glycyrrhizin, oral contraceptives, etc.), idiopathic edema, venous edema (eg, superior / inferior large vein syndrome, venous aneurysm) , Extremity vein thrombosis, venous valve insufficiency, etc.), Lymphatic edema (eg, congenital familial lymphedema, cancer metastasis, filariasis, etc.), Inflammatory edema (eg, vasculitis, allergies, etc.) (Caused by inflammation, etc.), vascular edema (eg, hereditary vascular edema, quinque edema, etc.) and the like.

In one aspect of the invention, edema includes edema in the upper body (eg, trunk, arms, etc.).

The active ingredient of the present invention can be used for comprehensive purposes including a plurality of uses (for example, 2 or more, 3 or more, 4 or more, 5 or more, 6 or more) among various uses.

In one aspect of the invention, the subject of the agent of the invention is an older person, eg, 40 years or older, preferably 50 years or older, more preferably 60 years or older, who is more likely to develop age-related edema. , More preferably it can be applied to people over the age of 65. Further, from the viewpoint of another classification, the agent of the present invention can be applied to, for example, middle-aged people, preferably elderly people. Furthermore, the active ingredient of the present invention can be used for the uses, purposes and objects listed below:
(A) For those who want to improve the quality of their muscles (b) For those who feel that their body is swollen (c) For those who think they are a little fat (d) For those who have a flat face (e) Clean and healthy For those who aim for the line (f) For those who are worried about taking too much salt (g) For those who feel that blood flow is stagnant (h) For those who are on a diet (i) For those who want to avoid fattening (i) j) For those who are worried about their face the next morning after drinking too much alcohol.

The agent of the present invention is used in various fields such as food compositions (including health foods, health enhancers, dietary supplements (supplements, etc.)), food additives, cosmetics, cosmetic additives, pharmaceuticals, reagents, feeds, etc. Can be used as. The agent of the present invention is preferably an oral composition.

The form of the agent of the present invention is not particularly limited, and can take a form usually used in each use depending on the intended use.

As the form of the agent of the present invention, when the use is a food composition, liquid, gel or solid foods such as juices, soft drinks, teas, soups, soymilk and other beverages, salad oils, dressings, yogurts and jellies. , Pudding, sprinkle, milk powder for childcare, cake mix, dairy products (eg, powder, liquid, gel, solid, etc.), bread, confectionery (eg, cookies, etc.) and the like.

When the use of the agent of the present invention is cosmetics, for example, milky lotion, cosmetic liquid, face cream, hand cream, lotion, body soap, shampoo, conditioner, cosmetic gel, facial mask, foundation, lip balm, face wash. Agents and the like can be mentioned.

When the use of the agent of the present invention is pharmaceutical, for example, an ointment, an external liquid agent (liniment agent, lotion agent, etc.), a spray agent (external aerosol agent, pump spray agent, etc.), a cream agent, a gel agent, etc. , Patches (plasters, tapes such as plasters (reservoir type, matrix type, etc.), paps, patches, microneedles, etc.), eye drops, eye ointments, nasal drops, suppositories, half for rectal Pharmaceutical form suitable for parenteral ingestion of solids, enema, etc. (particularly, external formulation); tablets (including medially disintegrating tablets, chewable tablets, effervescent tablets, troches, jelly-like drops, etc.), Pharmaceutical form suitable for oral ingestion such as rounds, granules, fine granules, powders, hard capsules, soft capsules, dry syrups, liquids (including drinks, suspensions and syrups), jelly (including drinks, suspensions and syrups) Oral formulation form).

As the form of the agent of the present invention, when the use is an additive, a health enhancer, a dietary supplement (supplement, etc.), for example, a tablet (intraoral disintegrating tablet, chewable tablet, effervescent tablet, troche agent, jelly) (Including pills and the like), pills, granules, fine granules, powders, hard capsules, soft capsules, dry syrups, liquids (including suspending agents and syrups), jelly agents and the like.

The agent of the present invention may further contain other components, if necessary. Other ingredients include ingredients that can be incorporated into food compositions (including health foods, health enhancers, dietary supplements (supplements, etc.)), food additives, cosmetics, cosmetic additives, pharmaceuticals, reagents, feeds, etc. As long as it is, the present invention is not particularly limited, but for example, a base, a carrier, a solvent, a dispersant, an emulsifier, a buffer, a stabilizer, an excipient, a binder, a disintegrant, a lubricant, a thickener, and a coloring agent. Examples include foodstuffs, fragrances, and chelating agents.

The content of the active ingredient in the agent of the present invention depends on the intended use, usage mode, state of application, etc., and is not limited, but is, for example, 0.0001 to 100% by mass, preferably 0.001 to 50% by mass. can do.

The amount of the agent of the present invention applied (for example, administration, ingestion, inoculation, etc.) is not particularly limited as long as it is an effective amount that exhibits an extracellular water ratio inhibitory effect, and is usually generally 1 as the dry weight of the active ingredient. The body weight is 0.1 to 10000 mg / kg per day. The above-mentioned application amount is preferably applied once or more once a day (for example, 1 to 3 times), and may be appropriately increased or decreased depending on the age, pathological condition, and symptom.

In a preferred embodiment of the present invention, the amount of Euglena applied (dry weight) is preferably 100 to 1000 mg, more preferably 250 to 750 mg, still more preferably 400 to 600 mg per day. It is preferably applied once a day, and is preferably applied daily. The application period is preferably 3 days or longer, more preferably 1 week or longer, further preferably 2 weeks or longer, still more preferably 4 weeks or longer, particularly preferably 6 weeks or longer, and particularly preferably 8 weeks or longer. Since the active ingredient of the present invention is naturally derived and highly safe, the upper limit of the applicable period is not particularly limited, but is, for example, 3 years, 1 year, 6 months, 3 months, or 2 months.

Hereinafter, the present invention will be described in detail based on examples, but the present invention is not limited to these examples.

Manufacturing example 1
Euglena Gracilis EOD-1 strain (NITE-IPOD, National Institute of Technology and Evaluation) dry powder (manufactured by Kobelco Eco-Solutions, paramylon content of 70% or more) in capsule tablets with the following composition Was used as a test meal, and a capsule tablet containing cornstarch as a control meal was produced.

Test Example 1
The outline of the test is as follows.
・ Test meal intake period: 8 weeks ・ Test meal intake: 2 capsules / day
・ Subjects: 30 (15 males, 15 females; 68.9 ± 3.1 years) (15 test meals, 15 control meals) * One of them (control meal) dropped out during the test, so it is reflected in the results. I didn't let you.

There were two types of test meals, a test meal and a control meal (placebo) (Production Example 1), the test meal was a food containing Euglena gracilis EOD-1 strain, and the control meal (placebo) was a food containing no Euglena gracilis EOD-1 strain. ..

Two capsules of the test meal were ingested once a day at dinner (in the test meal, 500 mg of Euglena gracilis EOD-1 strain (350 mg of paramylon derived from Euglena gracilis EOD-1 strain) was contained), and this was continued for 8 weeks. If it could not be taken at dinner, it was taken by bedtime on that day.

At the start date of the test (before the start of ingestion), 4 weeks after the start of the test, and 8 weeks after the start of the test (at the end of the test), a body composition analyzer (InBody, manufactured by Inbody Japan, BIA method (Bio). -The extracellular water ratio of the trunk and right arm was measured using an analyzer) by the electrical impedance analysis method). The extracellular water ratio is the measured extracellular water content (ECW: ExtraCellular Water) and the measured body water content (TBW: Total Body Water) (= extracellular water content + intracellular water content (ICW: IntraCelular Water). )) Is the value divided by.

The results obtained were statistically analyzed using IBM SPSS Statistics 25. The test was performed with the Mann-Whitney U test. A p-value less than 0.1 indicates significant.

The results are shown in FIGS. 1 and 2. Regarding the trunk, although no significant difference was obtained in this study, the extracellular water ratio tended to decrease in the test diet group as compared with the control diet group. Regarding the right arm, the extracellular water ratio was significantly lower in the test diet group than in the control diet group. From these results, it was found that the extracellular water ratio can be suppressed by ingesting Euglena.

Claims (10)

An extracellular water ratio inhibitor containing at least one selected from the group consisting of euglena, paramylon, processed paramylon, and β-1,3-glucan. The extracellular water ratio inhibitor according to claim 1, which comprises at least one selected from the group consisting of euglena, paramylon, and processed paramylon. The extracellular water ratio inhibitor according to claim 1 or 2, which contains the Euglena and the Euglena is Euglena gracilis. The extracellular water ratio inhibitor according to claim 1 or 2, which contains the Euglena and the Euglena is the Euglena gracilis EOD-1 strain (accession number FERM BP-11530). The extracellular water ratio inhibitor according to any one of claims 1 to 4, which is used for preventing or ameliorating edema. The edema is edema caused by decreased function of cell membrane, edema caused by impaired blood flow or decreased metabolism, age-related edema, renal edema, cardiac edema, hepatic edema, endocrine edema, nutritionally impaired edema. The extracellular water ratio suppression according to claim 5, which is at least one selected from the group consisting of drug-induced edema, idiopathic edema, venous edema, lymphatic edema, inflammatory edema, and vascular edema. Agent. The extracellular water ratio inhibitor according to claim 5 or 6, wherein the edema includes edema in the upper body. The extracellular water ratio inhibitor according to any one of claims 1 to 7, which is a food composition, a dietary supplement, a food additive, or a pharmaceutical. The extracellular water ratio inhibitor according to any one of claims 1 to 8, which is an oral composition. An agent for preventing or ameliorating edema, which comprises at least one selected from the group consisting of euglena, paramylon, processed paramylon, and β-1,3-glucan.

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