Acetaldehyde metabolism promoter

By employing an aldehyde metabolism promoter containing Euglena or β-1,3-glucan to enhance ALDH2 expression, the solution addresses the issue of low acetaldehyde metabolism, effectively reducing hangover and drunkenness symptoms and lowering blood acetaldehyde levels.

JP7696698B2Active Publication Date: 2025-06-23KOBELCO ECO SOLUTIONS CO LTD +1
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Patent Information

Application Number
JP2020103725
Authority / Receiving Office
JP · JP
Patent Type
Patents
Current Assignee / Owner
Filing Date
2020-06-16
Publication Date
2025-06-23
Estimated Expiration
2040-06-16

AI Technical Summary

Technical Problem

Current technologies do not effectively address the unpleasant symptoms of hangovers and severe drunkenness caused by low acetaldehyde metabolism, which is primarily dependent on the expression level of the ALDH2 enzyme.

Method used

The use of an aldehyde metabolism promoter containing Euglena, paramylon, processed paramylon, or β-1,3-glucan to enhance the expression level of ALDH2 in the liver, thereby promoting acetaldehyde metabolism and reducing blood acetaldehyde levels.

Benefits of technology

The proposed solution effectively suppresses hangover symptoms, reduces the severity of drunkenness, and lowers blood acetaldehyde levels, thereby alleviating discomfort after alcohol consumption and potentially reducing the risk of fatty liver and other health issues.

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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
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Description

Technical Field

[0001] The present invention relates to an acetaldehyde metabolism promoter and the like.

Background Art

[0002] Ethanol ingested by drinking affects brain function itself and causes drunkenness symptoms. Furthermore, acetaldehyde produced by the decomposition of ethanol in the body causes unpleasant symptoms of drunkenness such as nausea and headache. If the metabolism of this acetaldehyde is low, these unpleasant symptoms become stronger and longer, leading to hangovers and severe drunkenness. ALDH2 (aldehyde dehydrogenase 2) is an enzyme that decomposes acetaldehyde, and the level of acetaldehyde metabolism mainly depends on the level of ALDH2 expression (the presence or absence of ALDH2 gene deficiency).

[0003] Euglena is a microalgae belonging to the genus Euglena and is used as a food material. In addition, applying an Euglena extract to the skin has also been carried out (Patent Document 1). Also, 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 or β-1,3-glucan and acetaldehyde metabolism has not yet been clarified.

Prior Art Documents

Patent Documents

[0004]

Patent Document 1

Summary of the Invention

Problems to be Solved by the Invention

[0005] An object of the present invention is to provide an acetaldehyde metabolism promoter.

Means for Solving the Problems

[0006] As a result of intensive research in view of the above problems, the present inventors have found that the above problems can be solved if it is an aldehyde metabolism promoter containing at least one selected from the group consisting of Euglena, paramylon, processed paramylon, and β-1,3-glucan. As a result of further research based on this finding, the present invention has been completed. That is, the present invention includes the following aspects.

[0007] Item 1. An aldehyde metabolism promoter containing at least one selected from the group consisting of Euglena, paramylon, processed paramylon, and β-1,3-glucan.

[0008] Item 2. The aldehyde metabolism promoter according to Item 1, containing at least one selected from the group consisting of Euglena, paramylon, and processed paramylon.

[0009] Item 3. The aldehyde metabolism promoter according to Item 1 or 2, containing the Euglena, and the Euglena being Euglena gracilis.

[0010] Item 4. The aldehyde metabolism promoter according to Item 1 or 2, containing the Euglena, and the Euglena being Euglena gracilis strain EOD-1 (Accession No. FERM BP-11530).

[0011] Item 5. The aldehyde metabolism promoter according to any one of Items 1 to 4, containing the paramylon, and the paramylon being paramylon derived from Euglena gracilis.

[0012] Item 6. The aldehyde metabolism promoter according to any one of Items 1 to 5, for use in enhancing the expression level of ALDH2 in the liver.

[0013] Item 7. The aldehyde metabolism promoter according to any one of Items 1 to 6, for use in suppressing the blood aldehyde level.

[0014] Item 8. The acetaldehyde metabolism promoter according to any one of Items 1 to 7 for use in at least one selected from the group consisting of hangover suppression, nausea suppression, suppression of discomfort after drinking, suppression of heartburn after drinking, suppression of heaviness in the head after drinking, suppression of fatigue after drinking, drunkenness suppression, suppression of accumulation of neutral fat in the liver, fatty liver suppression, cancer suppression, and vasospastic angina pectoris.

[0015] Item 9. A composition containing at least one selected from the group consisting of Euglena, paramylon, processed paramylon, and β-1,3-glucan, for use in at least one selected from the group consisting of hangover suppression, nausea suppression, suppression of discomfort after drinking, suppression of heartburn after drinking, suppression of heaviness in the head after drinking, suppression of fatigue after drinking, drunkenness suppression, suppression of accumulation of neutral fat in the liver, fatty liver suppression, cancer suppression, and vasospastic angina pectoris.

[0016] Item 10. The acetaldehyde metabolism promoter according to any one of Items 1 to 9, which is a food composition, a dietary supplement, or a food additive.

[0017] Item 11. The acetaldehyde metabolism promoter according to any one of Items 1 to 10, which is an oral composition.

Advantages of the Invention

[0018] According to the present invention, an acetaldehyde metabolism promoter can be provided.

Brief Description of the Drawings

[0019]

Figure 1

Mode for Carrying Out the Invention

[0020] In this specification, the expressions "containing" and "comprising" include the concepts of "containing", "comprising", "consisting essentially of", and "consisting only of".

[0021] In one aspect, the present invention relates to an acetaldehyde metabolism promoter (which may also be referred to as "the agent of the present invention" in this specification) containing at least one selected from the group consisting of Euglena, paramylon, paramylon processed products, and β-1,3-glucan. This will be described below.

[0022] 1. Euglena Euglena is a microalgae belonging to the genus Euglena ( = Euglena), and is not particularly limited in that regard. Specifically, as Euglena, 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 Examples include the like. Among these, from the viewpoint of more surely exerting the effects of the present invention, Euglena gracilis is preferably mentioned, and more preferably Euglena gracilis EOD-1 strain [deposited internationally under the Budapest Treaty with the accession number FERM BP-11530 at the Patent Biological Depositary, National Institute of Technology and Evaluation (NITE-IPOD, Room 120, 2-5-8 Kazusa Kamashima, Kisarazu City, Chiba Prefecture 292-0818, Japan) on June 28, 2013] is mentioned.

[0023] The form of Euglena is not particularly limited as long as it contains most of the cell body of Euglena or its components. Examples of the form of Euglena include, for example, the dry powder form of Euglena, the suspension of Euglena, Euglena extract, etc. Among these, the dry powder form of Euglena is preferably mentioned.

[0024] The paramylon content in the dry state of Euglena is, for example, 50% or more, preferably 60% or more, more preferably 70% or more.

[0025] Euglena may be a single species or a combination of two or more species.

[0026] 2. β-1,3-glucan, paramylon β-1,3-glucan is not particularly limited as long as it has a single sugar chain (or sugar chain structure) in which glucose is linked only by β1,3 bonds as the main chain. β-1,3-glucan includes not only linear ones but also those having branched chains.

[0027] The weight average molecular weight of the β-1,3-glucan derivative is not particularly limited, but is, for example, 1×10 4 ~2×10 6 , preferably 5×10 4 ~1×10 6 , more preferably 1×10 5 ~1×10 6 . The weight average molecular weight can be measured by the GPC method.

[0028] β-1,3-glucan may be obtained by chemical synthesis, but from the viewpoint of easy availability, etc., natural β-1,3-glucan produced by various organisms is preferred. Examples of natural β-1,3-glucan include paramylon, curdlan, laminaran, callose, lentinan, schizophyllan, etc. Among these, paramylon is preferably mentioned. Hereinafter, paramylon will be described.

[0029] Paramylon is a β-1,3-glucan derived from Euglena and is not particularly limited in that regard.

[0030] Regarding the Euglena from which paramylon is derived, it is the same as the description in the above "1. Euglena".

[0031] The mass average molecular weight of paramylon is not particularly limited. For example, it is 1×10 4 ~5×10 6 Preferably, it is 2×10 4 ~1×10 6 More preferably, it is 5×10 4 ~1×10 6 Even more preferably, it is 1×10 5 ~5×10 5 and is.

[0032] In addition, the mass average molecular weight can be measured by SEC-MALS analysis under the following conditions: Detector: Multi-angle light scattering detector (DAWN HELEOS II manufactured by Wyatt Technology) Differential refractometer detector (Optilab T-rEX manufactured by Wyatt Technology) Columns used: Two TSKgel α-M (manufactured by Tosoh Corporation) Mobile phase: DMSO added with 0.05 M potassium bromide Flow rate: 0.5 mL / min.

[0033] Paramylon exists in Euglena cells usually as paramylon particles formed by highly aggregating triple helix structures formed by β-1,3-glucan chains on the basis of certain regularity.

[0034] The shape of paramylon particles is not particularly limited, but usually, it is a flat ellipsoid of revolution.

[0035] The particle size distribution of paramylon particles is not particularly limited, but for example, it is 0.5 to 15 μm, preferably 1 to 6 μm. Also, the average particle size of paramylon particles is not particularly limited, but for example, it is 1 to 10, preferably 2 to 4 μm.

[0036] The form of paramylon is not particularly limited as long as it contains paramylon. Examples of the form of Euglena include, for example, the dry powder form of paramylon, the suspension of paramylon, etc. Among them, preferably, the dry powder form of paramylon is mentioned.

[0037] Paramylon may be a single species or a combination of two or more species.

[0038] 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 (culturing step). The culturing step can be carried out, for example, according to a known method (for example, the method described in Japanese Patent No. 5883532). In this culturing step, typically, Euglena microalgae are cultured under aerobic conditions while stirring a liquid (culture solution) containing water, Euglena, and nutrients that Euglena can utilize.

[0039] Nutrients include saccharides (monosaccharides such as glucose (dextrose) and fructose), minerals (such as sodium, potassium, magnesium, calcium, iron, zinc, molybdenum, copper, phosphorus, nitrogen, sulfur, or boron, etc.), vitamin Bs (such as vitamin B1 (thiamine), vitamin B2 (riboflavin), niacin, pantothenic acid, vitamin B6 (pyridoxine, pyridoxal, or pyridoxamine), vitamin B12 (cyanocobalamin), folic acid, biotin, etc.), and the like. The concentration of nutrients in the culture solution is not particularly limited as long as it allows for the survival, growth, etc. of Euglena.

[0040] The light conditions in the culturing process are not particularly limited, and the culturing process may be carried out under either light conditions or dark conditions. When culturing in heterotrophic culture, it is cultured under dark conditions. As the light conditions, the normal light intensity for growing algae can be adopted. As the dark conditions, for example, less than 10 μmol / m 2 / s, preferably a complete dark condition where no light hits, can be mentioned.

[0041] The culturing temperature in the culturing process is not particularly limited as long as Euglena can grow. As the culturing temperature (the temperature of the culture solution), for example, 20°C to 35°C is adopted.

[0042] The pH of the liquid in the culturing process is not particularly limited as long as Euglena can grow. As the pH at which Euglena can grow, for example, 3.0 to 5.5 is adopted.

[0043] After the culturing process, it is preferable to concentrate Euglena by centrifugation or gravity separation of the liquid, etc. The obtained Euglena can be subjected to additional treatments (such as suspension in a liquid, dispersion in water or oil, extraction of extracts, drying and powdering, etc.) according to the desired form.

[0044] Paramylon particles can be produced by separating, isolating, or purifying them from Euglena according to or in accordance with known methods (for example, the method described in Japanese Patent No. 5883532). Paramylon particles can be easily obtained, for example, by recovering the intracellular components obtained by disrupting the cell membrane of Euglena. Further, if necessary, the paramylon particles may be purified. Various methods for purifying paramylon particles are known (for example, Japanese Patent No. 5883532), and they can be carried out according to those methods. Examples of the purification process include a surfactant treatment process, a washing process, and the like. The obtained Euglena can be subjected to additional treatments (for example, suspension in a liquid, dispersion in water or oil, drying and powdering, etc.) according to the desired form.

[0045] 4. Processed paramylon Paramylon processed products are obtained by subjecting paramylon to processing treatments, such as physical treatments, chemical treatments, etc., and are not particularly limited as long as they are within that scope. Examples of paramylon processed products include fibrillated paramylon, amorphous paramylon, and the like. Amorphous paramylon can be obtained by chemically treating it according to or in accordance with known methods, for example, using the method described in JP-A-2011-184592.

[0046] As the paramylon processed product, fibrillated paramylon is preferred. Fibrillated paramylon will be described below.

[0047] Fibrillated paramylon is a β-1,3-glucan derived from Euglena and is not particularly limited as long as it is in a fibrous form. So far, amorphous paramylon obtained by chemically treating paramylon particles (such as alkali treatment) has been reported, but this is not recognized as being fibrillated when observed with an electron microscope and is an irregularly shaped mass in terms of shape and size, and thus is not included in fibrillated paramylon.

[0048] The weight average molecular weight of fibrillated paramylon is not particularly limited, but for example, 1×10 4 ~2×107 Preferably, it is 1×10 5 ~5×10 5 .

[0049] The weight average molecular weight can be measured by SEC-MALS analysis in the following manner: Detector: Multi-angle light scattering detector (DAWN HELEOS II manufactured by Wyatt Technology) Differential refractometer detector (Optilab T-rEX manufactured by Wyatt Technology) Columns used: Two TSKgel α-M columns (manufactured by Tosoh Corporation) Mobile phase: DMSO added with 0.05 M potassium bromide Flow rate: 0.5 mL / min.

[0050] The diameter of the fibers of the fibrillated paramylon is not particularly limited, but for example, it is 10 to 500 nm, preferably 20 to 300 nm, more preferably 50 to 200 nm. The diameter of the fibers of the fibrillated paramylon can usually be measured based on the electron microscope image of the fibrillated paramylon.

[0051] The sedimentation volume of the fibrillated paramylon in water is not particularly limited, but for example, it is 30 to 300 mL / g, preferably 50 to 250 mL / g, more preferably 70 to 200 mL / g.

[0052] The sedimentation volume in water can be measured according to or in accordance with the following method: Measurement is carried out according to the method described in "Dietary Fiber - Basics and Applications - 3rd Edition, p.111, First Edition, Tokyo, published by Daiichi Shuppan, edited by the Editorial Committee of the Japanese Society for Dietary Fiber, supervised by the Japanese Society for Dietary Fiber (2008)". Specifically, it is as follows. A slurry-like test sample of the sample is weighed into a 25 mL plastic tube in an amount of 125 mg in terms of dry mass, and the plastic tube is shaken vigorously by hand to stir the contents. Then, the contents are transferred to a 25 mL graduated cylinder, and pure water is added until the volume reaches 25 mL. After stirring the liquid in the graduated cylinder, it is allowed to stand at 37 °C for 24 hours. As a result, the sample precipitates, and two layers (a layer mainly containing the precipitated sample (lower layer) and a layer mainly containing water (upper layer)) are formed through the interface. The volume of the lower layer is determined from the scale of the graduated cylinder, and the obtained volume is divided by the sample mass (dry mass) to calculate the sedimentation volume in water (mL / g). The test is performed three or four times, and the average value and standard deviation are calculated.

[0053] Fibrillated paramylon has relatively high resistance to enzymatic degradation. For example, the amount of monomers (glucose) produced by the degradation of β-glucanase is, per 1 g of fibrillated paramylon, for example, 0.1 to 50 mg, preferably 1 to 10 mg.

[0054] This amount can be measured according to or in accordance with the following method: Reaction solution [30 mg (dry weight) of the test substance, 5 mL of buffer solution (B0156 manufactured by Tokyo Chemical Industry Co., Ltd., potassium hydrogen phthalate - sodium hydroxide buffer (pH 4.0)), 0.1 mL of enzyme solution (endo - 1,3 - β - Glucanase manufactured by Nippon Biocon Co., Ltd. (enzyme content: 50 units / mL)), pure water, reaction solution volume 10 mL] was prepared and horizontally shaken at 40 °C for 24 hours at 45 rpm. After shaking, it was immediately stored frozen and freeze - dried for concentration. After freeze - drying, 0.5 mL of pure water was added to each sample and stirred (20 - fold concentration). The operation of centrifugation (10000G, 5 minutes, 4 °C) and collecting the supernatant was repeated twice. The glucose concentration in the collected supernatant was measured using a measurement kit (Glucose CII - Test Wako manufactured by Wako Pure Chemical Industries, Ltd.). Based on the measured value, the glucose production amount (mg) per 1 g of the test substance was calculated.

[0055] Fibrillated paramylon has relatively low solubility in alkaline solutions. For example, fibrillated paramylon does not dissolve in 0.1 - 0.3 M aqueous sodium hydroxide solution. Here, "does not dissolve" means that, for example, the absorbance (660 nm) of the solution after suspending fibrillated paramylon in the aqueous solution (for example, immediately after ~ 1 hour later) is, for example, 0.1 or more, preferably 1.0 or more.

[0056] Solubility can be measured according to or in accordance with the following method: 250 mg (dry weight) of the test substance is suspended in 10 mL of the test solution (pure water, 0.1 M NaOH aqueous solution, 0.3 M NaOH aqueous solution) in a vial. After shaking the vial vigorously by hand for 20 seconds and then shaking it on a shaker at 80 rpm for 1 hour, the absorbance at 660 nm of the liquid in the vial is measured respectively. The measurement of absorbance is performed using a spectrophotometer V - 730 manufactured by JASCO Corporation.

[0057] The relative value of the crystallinity of fibrillated paramylon to granular paramylon (crystallinity of fibrillated paramylon / crystallinity of granular paramylon) is, for example, 0.60 - 0.90, preferably 0.65 - 0.80.

[0058] The crystallinity can be measured according to or in accordance with the following method: For the test substance, XRD measurement is performed. The conditions are as follows. Instrument: PANalytical X’Pert3 Powder, tube voltage: 45 kV, tube current: 40 mA, measurement range: 5.005 - 50.018°, measurement interval: 0.013°, analysis software: HighScore. The crystallinity is analyzed by the ratio of the intensity of the amorphous part to the intensity of the crystalline part at 2θ = 5 - 80°. The analysis is carried out after removing the background by the device from each measurement data (background setting Auto, venting factor 0, granularity 100), and the amorphous part is determined by the tangent line passing through 2θ = 14, 29°. The conditions of the pending factor and granularity for determining each amorphous part are 0 / 20.

[0059] The fibrillated paramylon may be in a form dispersed in a solvent such as water or in a dry form. The fibrillated paramylon can be redispersed in water even in a dry form.

[0060] In this specification, the “dry form” means that the moisture content is 15% by mass or less, preferably 10% by mass or less, more preferably 5% by mass or less.

[0061] As the fibrillated paramylon, preferably, the defibrated product of paramylon particles obtained by physically defibrating the paramylon particles can be used. Also, the defibrated product of Euglena obtained by applying this defibrating treatment to Euglena can be used as the fibrillated paramylon.

[0062] The defibrination treatment is not particularly limited as long as it can defibrinate without substantially cleaving the hydrogen bonds of β-1,3 glucan present in paramylon particles (for example, cleaving no more than 10%, 5%, 2%, or 1% of the hydrogen bonds of β-1,3 glucan), or as long as it can dissolve part or all of the β-1,3-glucan chains present in paramylon particles or the triple helix structures formed thereby. Preferably, the defibrination treatment is performed without substantially cleaving the hydrogen bonds of β-1,3 glucan present in paramylon particles to make it fibrous. Known treatments capable of grinding (shearing) or pulverizing (preferably grinding (shearing)) fine particles such as paramylon particles can be employed as the defibrination treatment.

[0063] The defibrination treatment can be carried out using devices such as known grinding machines (shearing machines) and pulverizers. Examples of the devices used for the defibrination treatment include, for example, mortar-type grinding machines, jet mills, twin-screw kneaders, high-pressure homogenizers, high-pressure emulsifiers, twin-screw extruders, bead mills, and the like. Among these, mortar-type grinding machines and bead mills are preferably mentioned.

[0064] The defibrination treatment can be carried out either wet or dry. Performing the defibrination treatment wet is preferable as it enables more efficient dispersion of fibrillated paramylon in a solution. The solvent in the case of wet treatment is not particularly limited as long as it can disperse fibrillated paramylon, and water can be preferably used.

[0065] The defibrination treatment may be a single type or a combination of two or more types. Also, it may be paramylon that has been partially defibrinated, and as long as it contains defibrinated paramylon, it is within the scope intended by the present invention.

[0066] 5. Use At least one selected from the group consisting of Euglena, paramylon, processed paramylon, and β-1,3-glucan (hereinafter, may also be referred to as "the active ingredient of the present invention") has an enhancing effect on the ALDH2 expression level (particularly, the ALDH2 expression level in the liver). Therefore, the active ingredient of the present invention can be used for promoting acetaldehyde metabolism (specifically, for example, the metabolism of acetaldehyde to acetic acid) and further for suppressing the blood acetaldehyde level.

[0067] In addition, the active ingredient of the present invention can be used, for example, for suppressing hangover, suppressing severe drunkenness, suppressing discomfort after drinking, suppressing heartburn after drinking, suppressing heaviness in the head after drinking, suppressing fatigue after drinking, suppressing drunkenness, etc.

[0068] In addition, since the active ingredient of the present invention has an enhancing effect on the ALDH2 expression level, it can be used for suppressing the accumulation of neutral fat in the liver. In particular, people with a low-activity genotype of ALDH2 have a high risk of developing fatty liver due to drinking, so it is expected that the active ingredient of the present invention having an enhancing effect on the ALDH2 expression level can reduce the risk of onset. In addition, it is expected to reduce the risk of developing cancer and vasospastic angina due to smoking and drinking.

[0069] The active ingredient of the present invention can preferably be used for an inclusive use including a plurality (two or more, more preferably three or more, still more preferably four or more, even more preferably five or more, even more preferably six or more) of these uses.

[0070] Furthermore, the active ingredient of the present invention has the following uses, purposes, and targets: (a) People who want to support tomorrow's vitality (b) People who want to have a lively and energetic daily life (c) People who want to wake up refreshed (d) People who want to wake up feeling refreshed (e) People who are working busily (f) A new habit before a toast (g) People who want to maintain youthfulness (h) Those who are concerned about lack of stamina (i) It can also be used for nourishing and strengthening the body and relieving physical fatigue.

[0071] The agent of the present invention can be used in various fields, for example, as food compositions (including health foods, health promoters, nutritional supplements (such as supplements, etc.)), food additives, cosmetics, cosmetic additives, pharmaceuticals, reagents, feeds, etc. The agent of the present invention is preferably an oral composition.

[0072] The form of the agent of the present invention is not particularly limited, and depending on the use, it can take the form usually used in each use.

[0073] As the form of the agent of the present invention, when the use is a food composition, it includes liquid, gel-like or solid foods, such as beverages like juice, soft drinks, tea, soup, soy milk, salad oil, dressing, yogurt, jelly, pudding, furikake, powdered milk for infants, cake mix, dairy products (such as powdered, liquid, gel-like, solid, etc.), bread, confectioneries (such as cookies, etc.).

[0074] As the form of the agent of the present invention, when the use is cosmetics, it includes, for example, emulsion, lotion, face cream, hand cream, lotion, body soap, shampoo, conditioner, cosmetic gel, pack, foundation, lip cream, facial cleanser, etc.

[0075] As the dosage form of the agent of the present invention, when the use is for pharmaceuticals, for example, ointments, topical liquids (liniments, lotions, etc.), sprays (topical aerosols, pump sprays, etc.), creams, gels, patches (tape agents such as plasters and cataplasms (reservoir type, matrix type, etc.), poultices, patches, microneedles, etc.), eye drops, eye ointments, nasal drops, suppositories, semi-solid rectal agents, enemas, etc., dosage forms suitable for parenteral intake (particularly, topical dosage forms); tablets (including buccal disintegrating tablets, chewable tablets, effervescent tablets, troches, jelly drops, etc.), pills, granules, fine granules, powders, hard capsules, soft capsules, dry syrups, liquids (including drinks, suspensions, syrups), jelly agents, etc., dosage forms suitable for oral intake (oral dosage forms).

[0076] As the dosage form of the agent of the present invention, when the use is for additives, health promoters, nutritional supplements (such as supplements), etc., for example, tablets (including buccal disintegrating tablets, chewable tablets, effervescent tablets, troches, jelly drops, etc.), pills, granules, fine granules, powders, hard capsules, soft capsules, dry syrups, liquids (including suspensions, syrups), jelly agents, etc.

[0077] The agent of the present invention may further contain other components as necessary. The other components are not particularly limited as long as they are components that can be incorporated into food compositions (including health foods, health promoters, nutritional supplements (such as supplements)), food additives, cosmetics, cosmetic additives, pharmaceuticals, reagents, feeds, etc. Examples include bases, carriers, solvents, dispersants, emulsifiers, buffers, stabilizers, excipients, binders, disintegrants, lubricants, thickeners, colorants, fragrances, chelating agents, etc.

[0078] The content of the active ingredient in the agent of the present invention depends on the use, usage mode, condition of the application target, etc., and is not limited, but can be, for example, 0.0001 to 100% by mass, preferably 0.001 to 50% by mass.

[0079] The dosage of the agent of the present invention (for example, administration, ingestion, inoculation, etc.) is not particularly limited as long as it is an effective amount that exhibits the effect of enhancing the ALDH2 expression level. Usually, as the dry weight of the active ingredient, it is generally 0.1 to 10,000 mg / kg body weight per day. The above dosage is preferably applied in divided doses of once or more a day (for example, 1 to 3 times), and can be appropriately increased or decreased depending on age, disease state, and symptoms.

Examples

[0080] Hereinafter, the present invention will be described in detail based on examples, but the present invention is not limited by these examples.

[0081] Reference Example 1 As Euglena, dry powder of Euglena gracilis EOD-1 strain (manufactured by Shinko Environmental Solutions Co., Ltd., paramylon content 70% or more) of the National Institute of Technology and Evaluation Patent Biological Depositary Center (NITE-IPOD) was prepared.

[0082] Reference Example 2 Paramylon particles were prepared as follows.

[0083] The prepared Euglena gracilis EOD-1 strain (in the state before drying after culturing) was collected in five flasks of liquid, and the collected liquid was centrifuged (500×g, 4 minutes, room temperature) in a centrifuge tube. The supernatant in the centrifuge tube was removed and collected once. The collected supernatant was put into the centrifuge tube to disperse the precipitate in the centrifuge tube, and all of it was transferred to a 100 mL volumetric cylinder. Further, the collected supernatant was added to the volumetric cylinder to make up to 90 mL.

[0084] [Enzyme treatment step] The liquid made up to 90 mL was transferred to a 200 mL beaker, and the pH of the liquid was adjusted to 3 by adding an aqueous hydrochloric acid solution while stirring. A proteolytic enzyme (acid protease, product name "Protease YP-SS", manufactured by Yakult Pharmaceutical Industry Co., Ltd., optimal pH 2.5 - 3.0) was added to the liquid to a concentration of 5 g / L. The liquid was subjected to enzymatic treatment at 50 °C for 2 hours while stirring.

[0085] [Surfactant treatment step] An aqueous solution of sodium dodecyl sulfate was added to the liquid that had undergone the enzymatic treatment step so that the concentration of sodium dodecyl sulfate became 3.0 mass / volume (w / v)%. While stirring the liquid containing sodium dodecyl sulfate, the pH of the liquid was adjusted to 3 by adding an aqueous hydrochloric acid solution. Furthermore, the liquid was stirred at 60 °C for 30 minutes with a propeller stirrer (rotation speed 200 rpm).

[0086] [Separation step] 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. Except for the point of changing the concentration of sodium dodecyl sulfate to 1.0 mass / volume% and the point of not adjusting the pH, the surfactant treatment step was performed in the same manner. Then, the separation step was performed in the same manner as above. In this way, the surfactant treatment step and the separation step were each performed three times.

[0087] [Washing step] The paramylon precipitated by centrifugation in the separation step was suspended in pure water and allowed to stand at 40 °C for 10 minutes. Next, paramylon was precipitated by centrifugation (1000×g, 2 minutes, room temperature). Such operations were performed a total of three times.

[0088] [Drying step] The 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.

[0089] Test Example 1. Analysis of the effect on ALDH2 expression level Mice were fed with a diet containing paramylon (Reference Example 2) as food, and the ALDH2 expression level was measured. Specifically, it was carried out as follows.

[0090] <1-1. Test method> <1-1-1. Experimental animals and breeding conditions> Four-week-old male C57BL / 6J mice (manufactured by Charles River Japan, Inc.) were used. After preliminary breeding for one week with a solid diet (NMF, manufactured by Oriental Yeast Co., Ltd.), they were divided into three groups of 10 mice each so that their body weights were uniform.

[0091] The diets used in the test were as follows. Lard was added to the diets of the control group and the test group at 20% so that the fat energy ratio was 50%. Cellulose was added to the diet of the control group so that the dietary fiber weight ratio was 5%, and paramylon was added to the diet of the test group so that the dietary fiber weight ratio was 5%. The feed compositions of each group are shown in Table 1.

[0092]

Table 1

[0093] In the test, the mice were allowed to freely ingest the above diet and water for 87 days. The breeding environment was set at 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 last day of the test, the mice were fasted for 8 hours and euthanized with isoflurane / carbon dioxide gas. The liver was removed and stored in RNA later (Qiagen) to be used as a sample for RNA extraction.

[0094] <1-1-2. Measurement of ALDH2 expression level> RNA was extracted from the liver using the RNeasy mini kit (Qiagen), and the ALDH2 mRNA expression level was measured by real-time PCR. As primers, a forward primer represented by SEQ ID NO: 1 and a reverse primer represented by SEQ ID NO: 2 were used.

[0095] Also, as a reference, the 36B4 mRNA expression level was measured in the same manner. As primers, the forward primer represented by SEQ ID NO: 3 and the reverse primer represented by SEQ ID NO: 4 were used.

[0096] <1-2. Results> The results are shown in Fig. 1. As shown in Fig. 1, the test group (paramylon + high-fat diet) was significantly higher than the standard group (standard diet) and tended to be higher than the control group (high-fat diet) (p = 0.055). From this, it was found that paramylon (and Euglena containing it) has an effect of promoting aldehyde metabolism.

Claims

1. An oral composition containing at least one selected from the group consisting of Euglena and paramylon, for use in enhancing the expression level of ALDH2 in the liver.

2. The oral composition according to claim 1, which contains the Euglena and the Euglena is Euglena gracilis.

3. The oral composition according to claim 1, which contains the Euglena and the Euglena is the Euglena gracilis EOD-1 strain (accession number FERM BP-11530).

4. The oral composition according to claim 1, which contains the paramylon and the paramylon is paramylon derived from Euglena gracilis.

5. The oral composition according to claim 1, which contains the paramylon and the paramylon is paramylon derived from the Euglena gracilis EOD-1 strain (accession number FERM BP-11530).

6. The oral composition according to any one of claims 1 to 5, for use in suppressing the blood acetaldehyde level.

7. The oral composition according to any one of claims 1 to 6, for use in at least one selected from the group consisting of hangover suppression, nausea suppression, suppression of discomfort after drinking, suppression of heartburn after drinking, suppression of heaviness in the head after drinking, suppression of fatigue after drinking, drunkenness suppression, suppression of neutral fat accumulation in the liver, fatty liver suppression, cancer suppression, and vasospastic angina.

8. The oral composition according to any one of claims 1 to 7, which is a food composition or a food additive.

Citation Information

Patent Citations

  • Cosmetic or dermatological pharmaceutical composition containing Euglena extract

    JP2008526954A

  • Composition for relieving hangover or composition for preventing, alleviating or treating alcoholic liver disease, comprising β-glucan as active ingredient

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