JP2021193956A - Acetaldehyde metabolism promoter - Google Patents

Abstract

To provide an acetaldehyde metabolism promoter.SOLUTION: An acetaldehyde metabolism promoter contains at least one kind selected from the group consisting of Euglena, paramylum, paramylum processed product and β-1,3-glucan.SELECTED DRAWING: None

Description

The present invention relates to an acetaldehyde metabolism promoter and the like.

Ethanol ingested by drinking affects brain function by itself and causes sickness. Furthermore, acetaldehyde produced by the decomposition of ethanol in the body causes unpleasant symptoms of sickness such as nausea and headache. If the metabolism of acetaldehyde is low, these discomforts become stronger and longer, causing hangovers, hangovers, and the like. ALDH2 (aldehyde dehydrogenase 2) is an enzyme that decomposes acetaldehyde, and the level of acetaldehyde metabolism is mainly due to the high and low levels of ALDH2 expression (presence or absence of ALDH2 gene deficiency).

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). In addition, paramylon is a β-1,3-glucan produced by Euglena and has been reported to be useful for wound treatment and allergy suppression. However, the relationship between Euglena and β-1,3-glucan and acetaldehyde metabolism has not yet been clarified.

Special Table 2008-526954 Gazette

An object of the present invention is to provide an acetaldehyde metabolism promoter.

The present inventor has studied diligently in view of the above problems, and as a result, an acetaldehyde metabolism-promoting agent containing at least one selected from the group consisting of euglena, paramylon, processed paramylon, and β-1,3-glucan. If so, we have found that the above problems 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 acetaldehyde metabolism-promoting agent containing at least one selected from the group consisting of euglena, paramylon, processed paramylon, and β-1,3-glucan.

Item 2. Item 2. The acetaldehyde metabolism-promoting agent 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 acetaldehyde metabolism-promoting agent according to Item 1 or 2, which contains the Euglena and the Euglena is Euglena gracilis.

Item 4. Item 2. The acetaldehyde metabolism-promoting agent 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 6. The acetaldehyde metabolism-promoting agent according to any one of Items 1 to 4, which contains the paramylon and the paramylon is a paramylon derived from Euglena gracilis.

Item 6. Item 6. The acetaldehyde metabolism promoter according to any one of Items 1 to 5, which is used for enhancing the expression level of ALDH2 in the liver.

Item 7. Item 6. The acetaldehyde metabolism promoter according to any one of Items 1 to 6, which is used for suppressing blood acetaldehyde levels.

Item 8. Suppression of hangover, suppression of sickness, suppression of discomfort after drinking, suppression of chest burning after drinking, suppression of head congestion after drinking, suppression of fatigue after drinking, suppression of sickness, accumulation of neutral fat in the liver Item 6. The acetaldehyde metabolism-promoting agent according to any one of Items 1 to 7, for use in at least one selected from the group consisting of suppression, fatty liver suppression, cancer suppression, and vasospastic angover.

Item 9. Containing at least one selected from the group consisting of Euglena, paramylon, paramylon processed product, and β-1,3-glucan.
Suppression of hangover, suppression of sickness, suppression of discomfort after drinking, suppression of chest burning after drinking, suppression of head congestion after drinking, suppression of fatigue after drinking, suppression of sickness, accumulation of neutral fat in the liver A composition for use in at least one selected from the group consisting of suppression, fatty liver suppression, cancer suppression, and vasospastic angover.

Item 10. Item 6. The acetaldehyde metabolism-promoting agent according to any one of Items 1 to 9, which is a food composition, a dietary supplement, or a food additive.

Item 11. Item 6. The acetaldehyde metabolism-promoting agent according to any one of Items 1 to 10, which is an oral composition.

According to the present invention, an acetaldehyde metabolism promoter can be provided.

It is a graph which shows the measurement result of the ALDH2 expression level of Test Example 1. The vertical axis is the ratio of ALDH2 mRNA expression level in the liver to 36B4 mRNA expression level, which is a reference. In the horizontal axis, the control group was ingested with a high-fat diet supplemented with lard, and the test group was ingested with a high-fat diet supplemented with paramilon instead of cellulose contained in the high-fat diet. Yes, the standard group is the group fed the standard diet. It is shown that there is a significant difference (significant difference by Steel-Dwass test) between groups with different alphabets (p <0.05).

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 embodiment, comprises an acetaldehyde metabolism promoter (in the present specification, which comprises at least one selected from the group consisting of euglena, paramylon, processed paramylon, and β-1,3-glucan. 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 gracilis), Euglena longa, Euglena caudata, Euglena oxyuris, Euglena tripteris, Euglena proxima, Euglena viridis, Euglena sociabilis, Euglena ehrenbergii, Euglena deses, Euglena pisciformis, Euglena spirogyra, 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. The β-1,3-glucan is not limited to a linear one, but also includes one having a branched chain.

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 , and more preferably. 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:
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.

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 fibrotic 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 (Japan 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 on 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 conditions for the pending factor and granularity 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 its 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, a defibrated product of paramylon particles obtained by physically defibrating the paramylon particles can be preferably 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 part or all of the β-1,3-glucan chain present in the paramylon particles or the triple spiral structure formed by the chain. 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 grinding (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, and is the object 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") is an ALDH2 expression level (hereinafter, may be referred to as "active ingredient of the present invention"). In particular, it has an effect of increasing ALDH2 expression level in the liver). Therefore, the active ingredient of the present invention can be used for promoting acetaldehyde metabolism (specifically, for example, metabolism of acetaldehyde to acetic acid) and for suppressing blood acetaldehyde levels.

Further, the active ingredient of the present invention is, for example, suppression of hangover, suppression of sickness, suppression of discomfort after drinking, suppression of heartburn after drinking, suppression of head congestion after drinking, suppression of fatigue after drinking, suppression of sickness. It can be used for suppression and the like.

In addition, since the active ingredient of the present invention has an effect of increasing the expression level of ALDH2, it can be used to suppress the accumulation of triglyceride in the liver. In particular, since a person having a low-active genotype of ALDH2 has an increased risk of developing fatty liver due to drinking, it can be expected that the active ingredient of the present invention having an effect of increasing the expression level of ALDH2 will reduce the risk of developing fatty liver. In addition, it can be expected to reduce the risk of developing cancer and vasospasm angina due to smoking and drinking.

The active ingredient of the present invention is preferably plural (two or more, more preferably three or more, still more preferably four or more, even more preferably five or more, still more preferably six) of these uses. It can be used for comprehensive purposes including the above).

Furthermore, the active ingredient of the present invention has the following uses, purposes, and objects:
(A) People who want to support tomorrow's energy (b) People who want to live a healthy and lively life (c) People who want to wake up refreshingly (d) People who want to wake up refreshingly (e) People who are busy working (f) New habits before Kampai (g) People who want to keep youthful (h) People who are worried about lack of stamina (i) It can also be used for nutritional tonicity and physical fatigue.

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, powdered milk 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 suspensions and syrups), jelly 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 exerts an ALDH2 expression level enhancing effect, and is usually used as the dry weight of the active ingredient in general for one day. The body weight is 0.1 to 10000 mg / kg. 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.

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

Reference example 1
As Euglena, 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) was prepared.

Reference example 2
Paramylon particles were prepared as follows.

The prepared Euglena gracilis EOD-1 strain (after culturing and before drying) was collected for 5 flasks, and the collected liquid was centrifuged (500 × g, 4 minutes, room temperature) in a centrifuge tube. .. The supernatant liquid in the centrifuge tube was once removed and collected. The collected supernatant was placed in a centrifuge tube to disperse the precipitate in the centrifuge tube, and the whole was transferred to a graduated cylinder having a volume of 100 mL. Further, the collected supernatant was added to the measuring cylinder, and the solution was increased to 90 mL.

[Enzyme treatment process]
The pH of the liquid was adjusted to 3 by transferring the liquid prepared to 90 mL to a 200 mL beaker and adding an aqueous hydrochloric acid solution with stirring. A proteolytic enzyme (acidic protease product name "Protease YP-SS" manufactured by Yakult Pharmaceutical Co., Ltd., optimum pH 2.5 to 3.0) was added to the liquid so as to have a concentration of 5 g / L. The liquid was treated with an enzyme at 50 ° C. for 2 hours while stirring.

[Surfactant treatment process]
An aqueous solution of sodium dodecyl sulfate was added to the liquid that had undergone the enzyme treatment step so that the concentration of sodium dodecyl sulfate was 3.0% by mass / volume (w / v)%. The pH of the liquid was adjusted to 3 by adding an aqueous hydrochloric acid solution while stirring the liquid containing sodium dodecyl sulfate. Further, the liquid was stirred at 60 ° C. for 30 minutes with a propeller stirrer (rotation speed 200 rpm).

[Separation process]
Paramylon was precipitated by centrifugation (1000 × g, 2 minutes, room temperature), and paramylon was separated from the liquid that had undergone the surfactant treatment step. A surfactant treatment step was further carried out in the same manner except that the concentration of sodium dodecyl sulfate was changed to 1.0% by mass / volume% and the pH was not adjusted. Then, the separation step was performed in the same manner as above. In this way, the surfactant treatment step and the separation step were performed three times each.

[Washing process]
Paramylon precipitated by centrifugation in the separation step was suspended in pure water and allowed to stand at 40 ° C. for 10 minutes. Paramylon was then precipitated by centrifugation (1000 xg, 2 minutes, room temperature). Such an operation was performed a total of three times.

[Drying process]
Paramylon precipitated by centrifugation in the washing step was dried at 50 ° C. to obtain paramylon particles. The obtained paramylon particles were used as paramylon in the following test examples.

Test example 1. Analysis of effect on ALDH2 expression level Mice were bred on a feed containing paramylon (Reference Example 2), and the ALDH2 expression level was measured. Specifically, it was carried out as follows.

<1-1. Test method>
<1-1-1. Experimental animals and breeding conditions>
A 4-week-old male C57BL / 6J mouse (manufactured by Charles River Laboratories, Japan) was used. After pre-breeding for 1 week with solid feed (NMF, manufactured by Oriental Yeast Co., Ltd.), the animals were divided into 3 groups, 10 animals per group, so that the body weight would be uniform.

The feed used in the test is as follows. 20% lard was added to the control and test feeds to a fat energy ratio of 50%. Cellulose was added to the feed of the control group so that the dietary fiber weight ratio was 5%, and paramylon was added to the feed of the test group so that the dietary fiber weight ratio was 5%. The feed composition of each group is shown in Table 1.

In the test, mice were allowed to freely ingest the above feed and water for 87 days. The breeding environment was a temperature of 22 ± 1 ° C, a humidity of 50 ± 5%, and a 12-hour light-dark cycle (light period: 8:00 → 20:00, dark period: 20:00 → 8:00). On the final day of the test, they were fasted for 8 hours and euthanized with isoflurane / carbon dioxide. The liver was excised and stored in RNA later (Qiagen) as a sample for RNA extraction.

<1-1-2. Measurement of ALDH2 expression level>
After RNA was extracted from the liver using the RNeasy mini kit (Qiagen), the ALDH2 mRNA expression level was measured by the real-time PCR method. As the primer, the forward primer shown in SEQ ID NO: 1 and the reverse primer shown in SEQ ID NO: 2 were used.

As a reference, the expression level of 36B4 mRNA was also measured in the same manner. As the primer, the forward primer shown in SEQ ID NO: 3 and the reverse primer shown in SEQ ID NO: 4 were used.

<1-2. Result>
The results are shown in FIG. As shown in FIG. 1, the test group (paramylon + high-fat diet) tended to be significantly higher than the standard group (standard diet) and higher than the control group (high-fat diet) (p = 0.055). From this, it was found that paramylon (and Euglena containing it) has an acetaldehyde metabolism promoting action.

Claims (11)

An acetaldehyde metabolism-promoting agent containing at least one selected from the group consisting of euglena, paramylon, processed paramylon, and β-1,3-glucan. The acetaldehyde metabolism-promoting agent according to claim 1, which comprises at least one selected from the group consisting of euglena, paramylon, and processed paramylon. The acetaldehyde metabolism-promoting agent according to claim 1 or 2, which contains the Euglena and the Euglena is Euglena gracilis. The acetaldehyde metabolism-promoting agent 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 acetaldehyde metabolism-promoting agent according to any one of claims 1 to 4, which contains the paramylon and the paramylon is a paramylon derived from Euglena gracilis. The acetaldehyde metabolism-promoting agent according to any one of claims 1 to 5, which is used for enhancing the expression level of ALDH2 in the liver. The acetaldehyde metabolism-promoting agent according to any one of claims 1 to 6, which is used for suppressing blood acetaldehyde levels. Suppression of hangover, suppression of sickness, suppression of discomfort after drinking, suppression of chest burning after drinking, suppression of head congestion after drinking, suppression of fatigue after drinking, suppression of sickness, accumulation of neutral fat in the liver The acetaldehyde metabolism-promoting agent according to any one of claims 1 to 7, for use in at least one selected from the group consisting of suppression, fatty liver suppression, cancer suppression, and vasospastic angover. Containing at least one selected from the group consisting of Euglena, paramylon, paramylon processed product, and β-1,3-glucan.
Suppression of hangover, suppression of sickness, suppression of discomfort after drinking, suppression of chest burning after drinking, suppression of head congestion after drinking, suppression of fatigue after drinking, suppression of sickness, accumulation of neutral fat in the liver A composition for use in at least one selected from the group consisting of suppression, fatty liver suppression, cancer suppression, and vasospastic angover. The acetaldehyde metabolism-promoting agent according to any one of claims 1 to 9, which is a food composition, a dietary supplement, or a food additive. The acetaldehyde metabolism-promoting agent according to any one of claims 1 to 10, which is an oral composition.

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