WO2024080117A1 - Oral composition for preventing and/or improving cold symptoms - Google Patents

Oral composition for preventing and/or improving cold symptoms Download PDF

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WO2024080117A1
WO2024080117A1 PCT/JP2023/034691 JP2023034691W WO2024080117A1 WO 2024080117 A1 WO2024080117 A1 WO 2024080117A1 JP 2023034691 W JP2023034691 W JP 2023034691W WO 2024080117 A1 WO2024080117 A1 WO 2024080117A1
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group
test food
difference
groups
placebo group
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PCT/JP2023/034691
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French (fr)
Japanese (ja)
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綾香 中島
健吾 鈴木
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株式会社ユーグレナ
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    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/66—Microorganisms or materials therefrom
    • A61K35/74—Bacteria
    • A61K35/748—Cyanobacteria, i.e. blue-green bacteria or blue-green algae, e.g. spirulina
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/02—Nasal agents, e.g. decongestants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/04—Drugs for disorders of the respiratory system for throat disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/14—Antitussive agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]

Definitions

  • the present invention relates to an oral composition for preventing and/or improving cold symptoms.
  • Patent Document 1 describes a cold medicine composition that contains an antipyretic and analgesic drug such as ibuprofen.
  • Euglena is a single-celled microorganism classified as a microalgae. Because it has properties of both plants and animals, it contains a wide variety of nutrients, including vitamins, minerals, amino acids, and fatty acids. Since mass cultivation techniques for edible purposes were established in 2005, it has been used as a nutritional food and supplement to this day.
  • the object of the present invention is to provide an oral composition for preventing and/or improving cold symptoms.
  • an oral composition for preventing and/or ameliorating cold symptoms which contains a Euglena algae body substance.
  • the cold symptoms are preferably at least one selected from the group consisting of general malaise, chills, fever, fatigue, sneezing, runny nose, nasal congestion, sore throat, cough, joint pain, muscle pain, and headache.
  • the oral composition is preferably a food product.
  • the oral composition is preferably a beverage.
  • the oral composition may be a pharmaceutical product.
  • the present invention provides an oral composition for preventing and/or improving cold symptoms.
  • 1 is a graph showing the average cumulative number of days with cold symptoms over an 8-week period. Graph showing the mean severity of hot flashes over the entire period (8 weeks). Graph showing mean fatigue severity in the later period (last 4 weeks, periods V-VIII). 1 is a graph showing the mean severity of nasal congestion in the later period (last 4 weeks, periods V to VIII). Graph showing mean severity of sore throat in the later period (last 4 weeks, periods V-VIII). Graph showing the mean severity of muscle pain in the later period (last 4 weeks, periods V to VIII). 1 is a graph showing the change in the cumulative number of days with cold symptoms. 1 is a graph showing the change in cumulative number of fatigue days over time. 1 is a graph showing the total cumulative number of days of fatigue each week.
  • FIG. 13 is a diagram showing the cumulative percentage of each response regarding fatigue over the entire period (8 weeks).
  • FIG. 13 is a diagram showing the cumulative percentage of each response regarding sneezing over the entire period (8 weeks).
  • FIG. 13 is a graph showing the cumulative percentage of each response regarding nasal congestion over the entire period (8 weeks).
  • FIG. 13 is a diagram showing the cumulative percentage of each cough response over the entire period (8 weeks).
  • FIG. 13 is a diagram showing the cumulative percentage of each response regarding muscle pain over the entire period (8 weeks).
  • This embodiment relates to an oral composition for preventing and/or improving cold symptoms, and an agent for preventing and/or treating cold symptoms, which contains a substance derived from Euglena.
  • the preventive and/or therapeutic agent for cold symptoms according to this embodiment contains a Euglena-derived substance as an active ingredient and is used for preventing and/or treating cold symptoms.
  • Cold symptoms refers to at least one selected from the group consisting of general malaise, chills, fever, fatigue, sneezing, runny nose, nasal congestion, sore throat, cough, joint pain, muscle pain, and headache.
  • Prevention and/or treatment of cold symptoms refers to the concept of preventing, treating, alleviating, and improving cold symptoms.
  • the preventive and/or therapeutic agent for cold symptoms according to this embodiment can be used for at least one selected from the group consisting of relieving nasal discomfort, relieving runny nose, relieving nasal congestion, relieving itchy nose, relieving stuffy nose, relieving throat discomfort, relieving throat swelling, relieving redness in the throat, relieving a sore throat, relieving hoarseness, relieving phlegm, relieving chills, relieving tingling, relieving a feeling of sluggishness, relieving a feeling of hot flashes, relieving a feeling of daze, relieving a feeling of lethargy, relieving a feeling of lethargy, and relieving a feeling of fatigue.
  • the Euglena-derived substance includes dried Euglena algae, Euglena extract, and living Euglena cells, as well as paramylon extracted from Euglena cells, paramylon powder, and processed paramylon products.
  • Euglena includes microorganisms taxonomically classified in the genus Euglena, their variants, mutant species, and closely related species in the family Euglenaceae.
  • the genus Euglena refers to a group of organisms belonging to the Excavata, Euglenozoa, Euglenophyceae, Euglenales, and Euglenaceae families among eukaryotes.
  • Euglena chadefaudii Euglena deses, Euglena gracilis, Euglena granulata, Euglena mutabilis, Euglena proxima, Euglena spirogyra, and Euglena viridis.
  • Euglena Euglena gracilis
  • Euglena gracilis Z strain can be used, but other species such as Euglena gracilis Z strain mutant SM-ZK strain (chloroplast-deficient strain) and E. gracilis var. bacillaris variant, genetic mutants such as chloroplast mutants of these species, and other Euglena species such as Astasia longa can also be used.
  • the genus Euglena is widely distributed in freshwater such as ponds and swamps, and may be isolated from these for use, or any Euglena species that has already been isolated may be used.
  • the genus Euglena includes all mutant strains. These mutant strains also include those obtained by genetic methods such as recombination, transduction, transformation, etc.
  • Euglena algae bodies can be used as Euglena.
  • Euglena live cells separated by centrifugation, filtration, sedimentation, or the like can be used as they are as Euglena algae bodies.
  • Euglena live cells can be used as they are after harvesting from the culture tank, but it is preferable to wash them with water or physiological saline.
  • Euglena algae bodies may also be used in the form of a dispersion in which the Euglena algae bodies are dispersed in a liquid such as water.
  • mechanically treated algae bodies obtained by subjecting living Euglena cells to ultrasonic irradiation or mechanical treatment such as homogenization may be used as the Euglena algae bodies.
  • the mechanically treated product may be dried and used as the Euglena algae bodies.
  • defatted Euglena powder obtained by degreasing Euglena algae bodies for example, with a non-polar solvent.
  • a Euglena extract (Euglena extract) can be used as Euglena, and it is particularly preferable to use a Euglena aqueous solvent extract.
  • Euglena aqueous solvent extract refers to an extract extracted from Euglena using an aqueous solvent, and it is particularly preferable to use a water extract, hot water extract, alcohol extract, or glycol extract of Euglena extracted using water, alcohols, or glycols as the aqueous solvent at 5°C to 600°C for several seconds to several tens of hours.
  • the water used for extraction does not necessarily have to be distilled water, pure water, or ultrapure water, and may be, for example, tap water or water containing impurities, but water that does not contain components that interfere with the extraction of active ingredients is preferable.
  • water extract refers to an extract using water at 0 to 50°C (excluding 0°C).
  • water refers to water at 0 to 50°C (excluding 0°C).
  • the temperature of the water is not particularly limited as long as it is within a range in which the active ingredients can be sufficiently extracted without affecting them, but is preferably 1 to 40°C, more preferably 5 to 35°C, and particularly preferably 10 to 30°C.
  • hot water extract refers to an extract using water at a temperature higher than 50°C, and can also be called “warm water extract.”
  • hot water refers to water at a temperature higher than 50°C, and is a concept that includes “hot water,” including water in a boiling state. It is also not limited to hot water in a liquid state, but also includes hot water in a gaseous state and a supercritical state.
  • the temperature of the hot water is not particularly limited as long as it is within a range that can sufficiently extract the active ingredients without affecting them, but is preferably higher than 50°C and lower than 120°C, and more preferably higher than 50°C and lower than 100°C.
  • the pH of the water used for extraction is not particularly limited as long as it is within a range that allows the active ingredients to be sufficiently extracted without affecting them, but a pH of 4 to 10 is preferable, a pH of 5 to 9 is more preferable, and a pH of 6 to 8 is particularly preferable.
  • the aqueous solvent can be one that can sufficiently extract the active ingredient without affecting the active ingredient, and one or more solvents that can be normally used for extraction can be selected and used.
  • solvents that can be normally used for extraction
  • examples include water, alcohols, glycols, etc., but are not limited to these.
  • alcohols include ethanol, methanol, n-propanol, isopropanol, etc.
  • glycols include butylene glycol (BG) and propylene glycol, etc.
  • Other aqueous solvents include acetone, etc. These solvents can be used alone or as an aqueous solution, or as a mixed solvent of any two or more kinds.
  • the temperature of the aqueous solvent used for extraction is, for example, 0°C or higher, and is not particularly limited as long as it does not affect the active ingredients.
  • an aqueous solvent in a boiling or supercritical state can also be used, it is preferable to use an aqueous solvent at 5°C to 600°C, and it is more preferable to use an aqueous solvent at 10°C to 200°C. Therefore, aqueous solvents for extraction include aqueous solvents in a boiling or supercritical state.
  • the amount of aqueous solvent used for extraction is preferably an amount that can fully dissolve the water-soluble active ingredients contained in Euglena.
  • the extraction method is not particularly limited, and for example, extraction can be performed by the method shown below, but ordinary extraction methods can be freely selected and used without being limited thereto. Examples include a method in which dry powder of Euglena algae is soaked in an aqueous solvent for a predetermined time, followed by centrifugation or filtration, and a method in which dry powder of Euglena algae is added to an aqueous solvent, shaken to disperse uniformly, and then centrifuged or filtered. In addition, to promote extraction, it is also possible to heat the aqueous solvent after adding Euglena.
  • Water extraction of Euglena can be performed by a conventional method such as those shown below, but is not limited thereto.
  • Euglena tissue and water are placed in a container, and the container is left to stand for a predetermined time while being appropriately stirred or shaken.
  • the obtained extract can be used as it is as a water extract.
  • the supernatant obtained by centrifuging such an extract can also be used as a water extract.
  • the extract or supernatant can also be concentrated and dried to remove water, and used as a water extract.
  • Water extraction can be performed by adding a small amount of alcohol, for example, 10% by mass or less, preferably ethanol, to water in order to increase the extraction efficiency and shorten the extraction time.
  • the extraction time when performing water extraction is not particularly limited as long as it is a time that allows the active ingredient to be extracted, and can be set appropriately in the range of several seconds to several tens of hours depending on the extraction temperature.
  • Extraction using hot water can be performed by a commonly used method such as, but not limited to, the following.
  • Euglena is introduced into a commonly used extractor together with water, and then heated to perform extraction.
  • the pressure during extraction can be set to 1 to 5,000 atmospheres, and is preferably set to 60 to 400 atmospheres.
  • the extraction time is kept short, for example, within 3 minutes, more preferably within 1 minute, and especially preferably within 30 seconds.
  • the extracted Euglena extract can be used as it is as an active ingredient of the agent for preventing and/or treating cold symptoms according to this embodiment, but the extract can also be further fractionated by appropriate separation means (e.g., partition extraction, gel filtration, silica gel chromatography, reverse-phase or normal-phase high-performance liquid chromatography, etc.) to obtain highly active fractions for use.
  • the Euglena extract or a fraction thereof can be concentrated and dried to remove the aqueous solvent, and used as an aqueous solvent extract.
  • the Euglena extract may be a water-soluble component extracted by enzymatic proteolysis of algae cells belonging to the genus Euglena, specifically, a hydrolyzed Euglena extract obtained by enzymatic hydrolysis of Euglena powder (Euglena algae).
  • the hydrolyzed Euglena extract may be prepared according to the method described in JP 2010-90065 A.
  • the method for preparing hydrolyzed Euglena extract is explained below.
  • Purified water is added to the dried Euglena (weight), preferably in an amount 100 times (weight), and the mixture is subjected to a pressurized heat treatment.
  • a proteolytic enzyme is then added to treat the algae. After the treatment is complete, the mixture is inactivated, for example, at 90°C, and the residue is separated from the water-soluble components by centrifugation or filtration.
  • the conditions for the pressurized heat treatment are preferably heating and pressurizing at 100-150°C, atmospheric pressure to 0.255 MPa, and 1-30 minutes using an autoclave, for example, heating and pressurizing at 0.1-0.14 MPa and 121°C for 10 minutes.
  • the proteolytic enzyme for example, commonly used enzymes with protease activity such as pepsin, pancreatin, and papain may be used alone or in combination, and it is particularly preferable to use an endopeptidase to hydrolyze peptide bonds in the middle of the polypeptide chain and break it down into several peptides.
  • proteolytic enzymes that can be used include Yakult Pharmaceutical Co., Ltd.'s Panchidase MP and Aroase AP-10.
  • concentration of the enzyme to be added, the pH of the reaction solution, the reaction temperature, and other conditions can be selected to be optimal for each enzyme preparation.
  • the water-soluble component thus obtained can be used as is, but it can also be used after undergoing purification procedures such as fractionation, deodorization, decolorization, and concentration, within the scope that does not impair the effects of the present invention.
  • Polysaccharide contained in the genus Euglena, which is a polymer ( ⁇ -1,3-glucan) in which approximately 700 glucose molecules are polymerized through ⁇ -1,3-bonds.
  • Paramylon particles are flat spheroidal particles formed by entangling ⁇ -1,3-glucan chains in a spiral shape.
  • Paramylon exists as granules in the cells of all species and varieties of Euglena, and the number, shape, and uniformity of the particles vary depending on the species.
  • Paramylon consists only of glucose, and the average degree of polymerization of paramylon obtained from the wild strain of E. gracilis Z and the chloroplast-deficient strain SM-ZK is approximately 700 glucose units.
  • Paramylon is insoluble in water and hot water, but is soluble in dilute alkali, concentrated acid, dimethyl sulfoxide, formaldehyde, and formic acid.
  • the average density of paramylon is 1.53 in E. gracilis Z and 1.63 in E. gracilis var. bacillaris SM-L1.
  • paramylon has a loose spiral structure in which three linear ⁇ -1,3-glucans are twisted together like a right-handed rope. Several of these glucan molecules come together to form paramylon granules. Paramylon granules have a very high crystalline structure, accounting for approximately 90%, making it the compound with the highest crystalline structure rate among polysaccharides.
  • the particle size distribution of paramylon (manufactured by Euglena Co., Ltd.) has a median diameter of 1.5 to 2.5 ⁇ m when measured using a laser diffraction/scattering particle size distribution measuring device.
  • Paramylon particles are isolated from cultured Euglena cells by any suitable method, purified into fine particles, and usually provided as a powder.
  • paramylon particles can be obtained by (1) culturing Euglena cells in any suitable medium, (2) isolating Euglena cells from the medium, (3) isolating paramylon from the isolated Euglena cells, (4) purifying the isolated paramylon, and, if necessary, (5) cooling and subsequent freeze-drying.
  • Paramylon is isolated, for example, using a nonionic or anionic surfactant of a type that is largely biodegradable. Paramylon is purified substantially simultaneously with the isolation.
  • Processed paramylon products include water-soluble paramylon obtained by chemically or physically treating paramylon using various known methods, sulfated paramylon, and paramylon derivatives.
  • Processed paramylon products include, for example, amorphous paramylon and emulsion paramylon.
  • Amorphous paramylon is a substance in which crystalline paramylon derived from Euglena has been made amorphous.
  • Amorphous paramylon has a relative crystallinity of 1-20% compared to crystalline paramylon produced from Euglena by known methods. However, this relative crystallinity was determined by the method described in JP 2011-184592 A.
  • Amorphous paramylon is prepared according to the method described in JP 2011-184592 A by treating crystalline paramylon powder with an alkali, neutralizing it with acid, washing, removing moisture, and then drying.
  • Paramylon processed products also include water-soluble paramylon, obtained by chemically or physically processing paramylon using various known methods, sulfated paramylon, and paramylon derivatives.
  • Emsision paramylon is a substance also known as emulsion paramylon because its processing method and physical properties are similar to those of an emulsion. It is obtained by adding water to paramylon and carrying out a collision process in which the resulting fluid is ejected from a fine nozzle at ultra-high pressure and collided with an object to be impacted, according to the method described in JP 2016-199650 A, and is processed paramylon that has combined with more than four times its amount of water and swelled.
  • Emulsion paramylon can be obtained by performing a collision process at least once using a known property modification device (such as the device described in JP 2011-88108 A and JP 6-47264 A) in which a slurry of a powder or other solid with a water-soluble solvent is sprayed at ultra-high pressure from a fine nozzle and collided with a collision target, with a nozzle pressure of 245 MPa during spraying.
  • a known property modification device such as the device described in JP 2011-88108 A and JP 6-47264 A
  • a slurry of a powder or other solid with a water-soluble solvent is sprayed at ultra-high pressure from a fine nozzle and collided with a collision target, with a nozzle pressure of 245 MPa during spraying.
  • the median diameter is more than 7 ⁇ m, which is more than five times that of paramylon, and when observed using an optical electron microscope, the particles are observed to be attached to adjacent particles, and they swell by combining with more than four times as much water as paramylon.
  • the slurry made by mixing raw paramylon with water is a smooth fluid, but in emulsion paramylon, the paramylon disperses in the water molecules, increasing its viscosity and giving it a sticky, elastic texture that sticks to your hand when you touch it, like glue.
  • the processed paramylon obtained is called emulsion paramylon based on its processing method and physical properties, but it is unclear whether it is emulsified or not, and the paramylon is in a swollen state due to binding with water.
  • the preventive and/or therapeutic agent for cold symptoms is configured as an oral composition, for example, a food composition such as a health food or a pharmaceutical composition, and is used, ingested, or administered prophylactically and/or therapeutically to prevent and/or treat cold symptoms.
  • a food composition such as a health food or a pharmaceutical composition
  • the Euglena-derived substance can be ingested as a food and has no side effects, so it can be used, ingested, or administered continuously.
  • the agent for preventing and/or treating cold symptoms of this embodiment can provide a food composition having said effect by blending an effective amount of a Euglena-derived substance capable of effectively exerting a preventive and/or therapeutic effect on cold symptoms as a food ingredient into various foods. That is, in the field of food, the present invention can provide a food composition of a food labeled for anti-aging or the like. Examples of such food compositions include general foods, foods for specified health uses, foods with nutrient functions, foods with functional claims, foods for hospital patients, supplements, and the like. The food composition can also be used as a food additive.
  • Such food compositions include seasonings, processed meat products, processed agricultural products, beverages (lactic acid bacteria beverages, soft drinks, alcoholic beverages, carbonated beverages, dairy beverages, fruit juice beverages, tea, coffee, nutritional drinks, etc.), powdered beverages (powdered juice, powdered soup, etc.), concentrated beverages, confectioneries (candy (throat lozenges), cookies, biscuits, gum, gummies, chewables, tablets, chocolate, etc.), bread, cereals, etc.
  • the foods may be in the form of capsules, lozenges, syrup, granules, powder, etc.
  • a "specified health food” is a food that contains functional ingredients that affect physiological functions, etc., and can be labeled as suitable for a specific health purpose with the permission of the Commissioner of the Consumer Affairs Agency. In the present invention, it is a food that is sold with a label indicating a specific health purpose related to anti-aging.
  • Foods with nutrient functions are foods that are used to supplement nutritional components (vitamins, minerals) and display the function of the nutritional components. To be sold as such, the amount of nutritional components contained in the recommended daily intake must be within the range of set upper and lower limits, and in addition to displaying the nutritional functions, warning labels must also be included.
  • Foods with functional claims are foods that display functionality based on scientific evidence at the responsibility of the business operator. Information on safety and the basis for functionality is submitted to the Commissioner of the Consumer Affairs Agency before sale.
  • the food composition according to this embodiment can contain one or more freely selected ingredients that can be used in regular food compositions.
  • all additives that can be used regularly in the food industry such as various seasonings, preservatives, emulsifiers, stabilizers, flavorings, colorants, preservatives, and pH adjusters, can be included.
  • the agent for preventing and/or treating cold symptoms of this embodiment is a pharmaceutical composition having said effect, which can be provided by combining an amount of a Euglena-derived substance capable of effectively exerting an effect of preventing and/or treating cold symptoms with pharma- ceutical carriers and additives.
  • the pharmaceutical composition may be a drug or a quasi-drug.
  • the pharmaceutical composition is preferably applied internally (particularly orally), but may also be applied externally. Therefore, the pharmaceutical composition can be used in the form of an oral preparation, an injection such as an intravenous injection, a subcutaneous injection, an intradermal injection, an intramuscular injection and/or an intraperitoneal injection, a transmucosal application preparation, a transdermal application preparation, etc.
  • the dosage form of the pharmaceutical composition can be appropriately set depending on the form of application, and examples include solid preparations such as tablets, granules, capsules, powders, and dustings, liquid preparations such as solutions and suspensions, semi-solid preparations such as ointments or gels.
  • the pharmaceutical composition according to this embodiment can contain one or more pharma- ceutically acceptable additives of your choice.
  • the pharmaceutical composition according to this embodiment when applied to an oral preparation, it can contain all additives that are typically used in the field of pharmaceutical preparations, such as excipients, binders, disintegrants, surfactants, preservatives, colorants, flavorings, fragrances, stabilizers, preservatives, antioxidants, etc.
  • it can also be made into a sustained-release preparation by utilizing a drug delivery system (DDS).
  • DDS drug delivery system
  • the method of use of the preventive and/or therapeutic agent for cold symptoms and the food composition for preventing and/or improving cold symptoms of this embodiment may be, for example, orally administered in the form of capsules, powders, tablets, granules, liquids, syrups, etc.
  • the dosage and administration form of the preventive and/or therapeutic agent for cold symptoms and the food composition for preventing and/or improving cold symptoms of this embodiment may be appropriately selected depending on the subject, the disease state and its progression, and other conditions.
  • the Euglena-derived substance when orally administering to humans (adults) for the purpose of preventing and/or treating cold symptoms, is generally administered at a dose of 10 to 5,000 mg, preferably 500 to 5,000 mg, and more preferably 1,000 to 5,000 mg of Euglena per day in dry weight.
  • the frequency of administration is preferably several times a week, once every two days, once a day, or more, more preferably two or more times a day, and even more preferably three times a day, preferably in the morning, midday, and evening, specifically after each meal (after breakfast, lunch, and dinner).
  • the administration should be long-term or sustained, for example, for a period of 5 weeks or more, preferably 8 weeks or more.
  • Euglena algae it is preferable to ingest 500 mg or more of Euglena algae as a Euglena-derived substance per day for at least five weeks.
  • Test food compositions of Example 1 (test food group) and Comparative Example 1 (placebo group) are shown in the following Tables 1 and 2.
  • Euglena gracilis powder Euglena algae, manufactured by Euglena Co., Ltd. was used as Euglena.
  • test food composition was in the form of a hard capsule and packaged in an aluminum pouch. After opening the package, it was stored in the refrigerator.
  • ⁇ Test Effect of Euglena intake on the occurrence of cold symptoms> Men and women in their 20s to 80s were asked to continue taking capsules containing 1,000 mg of Euglena per day (test food group) or placebo capsules (placebo group) for eight weeks, and the presence or absence of cold symptoms was recorded daily.
  • the test was a double-blind study. Participants were asked to answer questions about cold symptoms, including 1. "general malaise,” 2. “chills,” 3. “feeling feverish,” 4. “fatigue,” 5. “sneezing,” 6. “runny nose,” 7. “nasal congestion,” 8. “sore throat,” 9. “cough,” 10. "joint pain,” 11. “muscle pain,” and 12. "headache,” on a five-point scale from 1 to 5 (1. “not at all,” 2. “hardly any,” 3. “a little,” 4. “somewhat,” 5. “severe”). Participants were judged to have developed symptoms if they answered 3 to 5, and the cumulative number of days each symptom developed and the maximum duration during the intake period were recorded.
  • the presence of one or more of the following symptoms was defined as cold symptoms: general malaise, chills, fever, fatigue, sneezing, runny nose, nasal congestion, sore throat, cough, joint pain, muscle pain, or headache.
  • the day on which a response other than 1 or 2 was given on or after the second day after response 1 was defined as the onset date of said symptom or cold symptoms (if a response other than 1 or 2 was given on the first or second day after starting intake, that day was also included in the onset date).
  • the cumulative number of days with cold symptoms, maximum duration, severity, number of cases, cumulative number of days with onset, etc. were recorded.
  • Period I The period from the start of intake to the 7th day of intake will be Period I
  • the period from the 8th to the 14th day will be Period II
  • each subsequent period will be determined as one week apart, with the final week (from the 50th to the 56th day of intake) being Period VIII.
  • the cumulative number of days with cold symptoms (average) from weeks 5 to 8 was significantly less in the Euglena intake group than in the placebo intake group. More specifically, as shown in Figures 2A to 2E, the average severity of feverishness and fatigue over the entire period (8 weeks) was significantly lower in the Euglena intake group than in the placebo intake group, and the average severity of nasal congestion, sore throat, and muscle pain in the later period (last 4 weeks) was significantly lower.
  • Proportion of cough severity level 1 Among the periods in which significant differences were observed, the periods in which the test food group showed higher values than the placebo group were the entire period (placebo group: 82.7%, test food group: 88.8%, difference between groups: 6.1% [4.8, 7.3], P ⁇ 0.001), the early period (placebo group: 82.6%, test food group: 88.2%, difference between groups: 5.6% [3.8, 7.4], P ⁇ 0.001), and the late period (placebo group: 82.8%, test food group: 89.4%, difference between groups: 6.6% [4.9, 8.4], P ⁇ 0.001).
  • the primary outcome of this study was the mean and standard deviation of the cumulative number of days with cold symptoms for each participant over the entire period: 15.9 ⁇ 17.5 days for the test food group and 21.3 ⁇ 19.2 days for the placebo group.
  • the difference between the groups and its 95% confidence interval was -5.4 days [-10.4, -0.5], meaning that the cumulative number of days with cold symptoms was significantly less in the test food group than in the placebo group.
  • the cumulative number of days with cold symptoms in the test food group was significantly lower than in the placebo group throughout the entire period and in the early and late periods, and the cumulative number of days with each of the following symptoms was also significantly lower in the test food group: general malaise, chills, fatigue, sneezing, runny nose, nasal congestion, sore throat, cough, and muscle pain.

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Abstract

Provided is an oral composition for preventing and/or improving cold symptoms.　This oral composition for preventing and/or improving cold symptoms contains euglena algae. It is preferable for the cold symptoms in this case to be one or more symptoms selected from the group consisting of general malaise, chills, feverishness, fatigue, sneezing, nasal discharge, nasal congestion, sore throat, coughing, joint pain, myalgia and headache. It is preferable for the oral consumption to be a food product, a beverage or a medicine.

Description

感冒症状の予防及び／又は改善用経口組成物Oral composition for preventing and/or improving cold symptoms
　本発明は、感冒症状の予防及び／又は改善用経口組成物に関する。 The present invention relates to an oral composition for preventing and/or improving cold symptoms.
　風邪は、最もありふれた疾患である。風邪などに罹患した際に生じる全身倦怠感や寒気等の感冒症状が生活上、問題となる。対症療法薬として、感冒症状を緩和する効果を出すように設計された感冒薬が開発され、ＯＴＣ医薬品として販売されている。例えば、特許文献１には、イブプロフェンなどの解熱鎮痛薬を含有する感冒薬組成物が記載されている。 　The common cold is the most common illness. When one is infected with a cold, cold symptoms such as general fatigue and chills become a problem in daily life. As symptomatic treatments, cold medicines designed to alleviate cold symptoms have been developed and are sold as over-the-counter drugs. For example, Patent Document 1 describes a cold medicine composition that contains an antipyretic and analgesic drug such as ibuprofen.
　ユーグレナは、微細藻類に分類される単細胞の微生物である。植物と動物両方の性質を兼ね備えていることから、ビタミン、ミネラル、アミノ酸、脂肪酸等多様な栄養素を含んでいる。２００５年に食用の大量培養技術が確立されて以降、今日に至るまで栄養補助食品やサプリメントとして活用されている。 Euglena is a single-celled microorganism classified as a microalgae. Because it has properties of both plants and animals, it contains a wide variety of nutrients, including vitamins, minerals, amino acids, and fatty acids. Since mass cultivation techniques for edible purposes were established in 2005, it has been used as a nutritional food and supplement to this day.
特開２００８－１４３８０７号公報JP 2008-143807 A
　感冒症状を予防及び改善することが求められている。本発明の目的は、感冒症状の予防及び／又は改善用経口組成物を提供することにある。 There is a need to prevent and improve cold symptoms. The object of the present invention is to provide an oral composition for preventing and/or improving cold symptoms.
　前記課題は、ユーグレナ藻体物質を含有する感冒症状の予防及び／又は改善用経口組成物により解決される。
　このとき、前記感冒症状は、全身倦怠感、寒気、熱っぽさ、疲労、くしゃみ、鼻汁、鼻閉、のどの痛み、せき、関節痛、筋肉痛、頭痛からなる群より選択される少なくとも１種であるとよい。
　このとき、鼻の不快感の軽減、鼻みずの軽減、鼻づまりの軽減、鼻の痒みの軽減、鼻のむずむず感の軽減、喉の不快感の軽減、のどの腫れの軽減、のどの赤味の軽減、のどのイガイガの軽減、声がれの軽減、たんの軽減、悪寒の軽減、ゾクゾク感の軽減、グズグズ感の軽減、ほてり感の軽減、ぼーっと感の軽減、めまいの軽減、ぐったり感の軽減、無気力感の軽減、体のだるさの軽減からなる群より選択される少なくとも１種のために用いられるとよい。
　このとき、前記ユーグレナ藻体が１日あたり５００ｍｇ以上で５週間以上継続して摂取されるとよい。
　このとき、前記経口組成物が食品であるとよい。
　このとき、前記経口組成物が飲料であるとよい。
　このとき、前記経口組成物が医薬品であるとよい。 The above-mentioned problems are solved by an oral composition for preventing and/or ameliorating cold symptoms, which contains a Euglena algae body substance.
In this case, the cold symptoms are preferably at least one selected from the group consisting of general malaise, chills, fever, fatigue, sneezing, runny nose, nasal congestion, sore throat, cough, joint pain, muscle pain, and headache.
In this case, it is preferable to use it for at least one selected from the group consisting of relieving nasal discomfort, relieving runny nose, relieving nasal congestion, relieving itchy nose, relieving stuffy nose, relieving throat discomfort, relieving throat swelling, relieving redness in the throat, relieving a sore throat, relieving hoarseness, relieving phlegm, relieving chills, relieving tingling, relieving a feeling of lethargy, relieving a feeling of hot flashes, relieving a feeling of daze, relieving a feeling of lethargy, relieving a feeling of lethargy, and relieving bodily fatigue.
In this case, it is preferable to continuously ingest the Euglena algae at a dose of 500 mg or more per day for 5 weeks or more.
In this case, the oral composition is preferably a food product.
In this case, the oral composition is preferably a beverage.
In this case, the oral composition may be a pharmaceutical product.
　本発明によれば、感冒症状の予防及び／又は改善用経口組成物を提供できる。 The present invention provides an oral composition for preventing and/or improving cold symptoms.
８週間の感冒症状累積日数平均値を示すグラフである。1 is a graph showing the average cumulative number of days with cold symptoms over an 8-week period. 全期間（８週間）における熱っぽさの重症度の平均値を示すグラフである。Graph showing the mean severity of hot flashes over the entire period (8 weeks). 後期（後半４週間、期間Ｖ～ＶＩＩＩ）における疲労の重症度の平均値を示すグラフである。Graph showing mean fatigue severity in the later period (last 4 weeks, periods V-VIII). 後期（後半４週間、期間Ｖ～ＶＩＩＩ）における鼻閉の重症度の平均値を示すグラフである。1 is a graph showing the mean severity of nasal congestion in the later period (last 4 weeks, periods V to VIII). 後期（後半４週間、期間Ｖ～ＶＩＩＩ）におけるのどの痛みの重症度の平均値を示すグラフである。Graph showing mean severity of sore throat in the later period (last 4 weeks, periods V-VIII). 後期（後半４週間、期間Ｖ～ＶＩＩＩ）における筋肉痛の重症度の平均値を示すグラフである。Graph showing the mean severity of muscle pain in the later period (last 4 weeks, periods V to VIII). 感冒症状の累積日数の推移を示すグラフである。1 is a graph showing the change in the cumulative number of days with cold symptoms. 疲労の累積日数の推移を示すグラフである。1 is a graph showing the change in cumulative number of fatigue days over time. 各週の疲労の累積日数の合計値を示すグラフである。1 is a graph showing the total cumulative number of days of fatigue each week. 各週のくしゃみの累積日数の合計値を示すグラフである。1 is a graph showing the total cumulative number of days with sneezing each week. 各週の鼻汁の累積日数の合計値を示すグラフである。1 is a graph showing the total cumulative number of days with nasal runny nose each week. 各週の鼻閉の累積日数の合計値を示すグラフである。1 is a graph showing the total cumulative number of days with nasal congestion each week. 各週ののどの痛みの累積日数の合計値を示すグラフである。1 is a graph showing the total cumulative number of days with sore throat each week. 各週のせきの累積日数の合計値を示すグラフである。1 is a graph showing the total cumulative number of days with cough each week. 各週の筋肉痛の累積日数の合計値を示すグラフである。1 is a graph showing the total cumulative number of days with muscle pain each week. 全期間（８週間）における疲労の各回答の累積値割合を示す図である。FIG. 13 is a diagram showing the cumulative percentage of each response regarding fatigue over the entire period (8 weeks). 全期間（８週間）におけるくしゃみの各回答の累積値割合を示す図である。FIG. 13 is a diagram showing the cumulative percentage of each response regarding sneezing over the entire period (8 weeks). 全期間（８週間）における鼻閉の各回答の累積値割合を示す図である。FIG. 13 is a graph showing the cumulative percentage of each response regarding nasal congestion over the entire period (8 weeks). 全期間（８週間）におけるせきの各回答の累積値割合を示す図である。FIG. 13 is a diagram showing the cumulative percentage of each cough response over the entire period (8 weeks). 全期間（８週間）における筋肉痛の各回答の累積値割合を示す図である。FIG. 13 is a diagram showing the cumulative percentage of each response regarding muscle pain over the entire period (8 weeks).
　以下、本発明の実施形態について図１乃至図５Ｅを参照して説明する。本実施形態は、ユーグレナ由来物質を含有する感冒症状の予防及び／又は改善用経口組成物、感冒症状の予防及び／又は治療剤に関するものである。 Below, an embodiment of the present invention will be described with reference to Figs. 1 to 5E. This embodiment relates to an oral composition for preventing and/or improving cold symptoms, and an agent for preventing and/or treating cold symptoms, which contains a substance derived from Euglena.
＜感冒症状の予防及び／又は治療剤＞
　本実施形態に係る感冒症状の予防及び／又は治療剤は、ユーグレナ由来物質を有効成分として含有し、感冒症状を予防及び／又は治療するために用いられるものである。 <Agent for preventing and/or treating cold symptoms>
The preventive and/or therapeutic agent for cold symptoms according to this embodiment contains a Euglena-derived substance as an active ingredient and is used for preventing and/or treating cold symptoms.
　「感冒症状」とは、全身倦怠感、寒気、熱っぽさ、疲労、くしゃみ、鼻汁、鼻閉、のどの痛み、せき、関節痛、筋肉痛、頭痛からなる群より選択される少なくとも１種である。「感冒症状の予防及び／又は治療」とは、感冒症状を予防、治療、緩和、改善することを含む概念である。 "Cold symptoms" refers to at least one selected from the group consisting of general malaise, chills, fever, fatigue, sneezing, runny nose, nasal congestion, sore throat, cough, joint pain, muscle pain, and headache. "Prevention and/or treatment of cold symptoms" refers to the concept of preventing, treating, alleviating, and improving cold symptoms.
　本実施形態に係る感冒症状の予防及び／又は治療剤は、鼻の不快感の軽減、鼻みずの軽減、鼻づまりの軽減、鼻の痒みの軽減、鼻のむずむず感の軽減、喉の不快感の軽減、のどの腫れの軽減、のどの赤味の軽減、のどのイガイガの軽減、声がれの軽減、たんの軽減、悪寒の軽減、ゾクゾク感の軽減、グズグズ感の軽減、ほてり感の軽減、ぼーっと感の軽減、めまいの軽減、ぐったり感の軽減、無気力感の軽減、体のだるさの軽減からなる群より選択される少なくとも１種のために用いることができる。 The preventive and/or therapeutic agent for cold symptoms according to this embodiment can be used for at least one selected from the group consisting of relieving nasal discomfort, relieving runny nose, relieving nasal congestion, relieving itchy nose, relieving stuffy nose, relieving throat discomfort, relieving throat swelling, relieving redness in the throat, relieving a sore throat, relieving hoarseness, relieving phlegm, relieving chills, relieving tingling, relieving a feeling of sluggishness, relieving a feeling of hot flashes, relieving a feeling of daze, relieving a feeling of lethargy, relieving a feeling of lethargy, and relieving a feeling of fatigue.
＜ユーグレナ由来物質＞
　本実施形態において、ユーグレナ由来物質とは、ユーグレナの乾燥藻体、ユーグレナ抽出物、ユーグレナ生細胞のほか、ユーグレナ細胞から抽出されたパラミロン、パラミロン粉末や、パラミロンの加工品等が含まれる。 <Substances derived from Euglena>
In this embodiment, the Euglena-derived substance includes dried Euglena algae, Euglena extract, and living Euglena cells, as well as paramylon extracted from Euglena cells, paramylon powder, and processed paramylon products.
＜ユーグレナ＞
　本実施形態において、「ユーグレナ」とは、分類学上、ユーグレナ属（Ｅｕｇｌｅｎａ）に分類される微生物、その変種、その変異種及びユーグレナ科（Ｅｕｇｌｅｎａｃｅａｅ）の近縁種を含む。ここで、ユーグレナ属（Ｅｕｇｌｅｎａ）とは、真核生物のうち、エクスカバータ、ユーグレノゾア門、ユーグレナ藻綱、ユーグレナ目、ユーグレナ科に属する生物の一群である。 <Euglena>
In this embodiment, "Euglena" includes microorganisms taxonomically classified in the genus Euglena, their variants, mutant species, and closely related species in the family Euglenaceae. Here, the genus Euglena refers to a group of organisms belonging to the Excavata, Euglenozoa, Euglenophyceae, Euglenales, and Euglenaceae families among eukaryotes.
　ユーグレナ属に含まれる種として、具体的には、Euglena chadefaudii、Euglena deses、Euglena gracilis、Euglena granulata、Euglena mutabilis、Euglena proxima、Euglena spirogyra、Euglena viridisなどが挙げられる。ユーグレナとして、ユーグレナ・グラシリス（E. gracilis），特に、ユーグレナ・グラシリス（E. gracilis）Ｚ株を用いることができるが、そのほか、ユーグレナ・グラシリス（E. gracilis）Ｚ株の変異株ＳＭ－ＺＫ株（葉緑体欠損株）や変種のE. gracilis var. bacillaris、これらの種の葉緑体の変異株等の遺伝子変異株、Astasia longa等のその他のユーグレナ類であってもよい。 Specific examples of species that belong to the genus Euglena include Euglena chadefaudii, Euglena deses, Euglena gracilis, Euglena granulata, Euglena mutabilis, Euglena proxima, Euglena spirogyra, and Euglena viridis. As Euglena, Euglena gracilis, in particular Euglena gracilis Z strain, can be used, but other species such as Euglena gracilis Z strain mutant SM-ZK strain (chloroplast-deficient strain) and E. gracilis var. bacillaris variant, genetic mutants such as chloroplast mutants of these species, and other Euglena species such as Astasia longa can also be used.
　ユーグレナ属は、池や沼などの淡水中に広く分布しており、これらから分離して使用しても良く、また、既に単離されている任意のユーグレナ属を使用してもよい。ユーグレナ属は、その全ての変異株を包含する。また、これらの変異株の中には、遺伝的方法、たとえば組換え、形質導入、形質転換等により得られたものも含有される。 The genus Euglena is widely distributed in freshwater such as ponds and swamps, and may be isolated from these for use, or any Euglena species that has already been isolated may be used. The genus Euglena includes all mutant strains. These mutant strains also include those obtained by genetic methods such as recombination, transduction, transformation, etc.
（ユーグレナ藻体）
　本実施形態では、ユーグレナとしてユーグレナ藻体を用いることが可能である。ユーグレナ藻体として、遠心分離，濾過又は沈降等によって分離したユーグレナ生細胞をそのまま用いることができる。ユーグレナ生細胞は、培養槽から収穫後そのままの状態で使用することもできるが、水若しくは生理食塩水で洗浄するのが好ましい。また、ユーグレナ藻体が水などの液体に分散した分散液の状態で用いてもよい。本実施形態において、ユーグレナ生細胞を凍結乾燥処理やスプレー乾燥処理して得たユーグレナの乾燥藻体（ユーグレナ粉末）をユーグレナ藻体として用いると好適である。 (Euglena algae)
In this embodiment, Euglena algae bodies can be used as Euglena. Euglena live cells separated by centrifugation, filtration, sedimentation, or the like can be used as they are as Euglena algae bodies. Euglena live cells can be used as they are after harvesting from the culture tank, but it is preferable to wash them with water or physiological saline. Euglena algae bodies may also be used in the form of a dispersion in which the Euglena algae bodies are dispersed in a liquid such as water. In this embodiment, it is preferable to use dried Euglena algae bodies (Euglena powder) obtained by freeze-drying or spray-drying live Euglena cells as Euglena algae bodies.
　更に、ユーグレナ生細胞を超音波照射処理や、ホモゲナイズ等の機械処理を行うことにより得た藻体の機械的処理物をユーグレナ藻体として用いてもよい。また、機械的処理物に乾燥処理を施した機械的処理物乾燥物をユーグレナ藻体として用いてもよい。さらに、ユーグレナ藻体を、例えば無極性溶媒により脱脂処理を施した脱脂ユーグレナ粉末を用いることも可能である。 Furthermore, mechanically treated algae bodies obtained by subjecting living Euglena cells to ultrasonic irradiation or mechanical treatment such as homogenization may be used as the Euglena algae bodies. Furthermore, the mechanically treated product may be dried and used as the Euglena algae bodies. Furthermore, it is also possible to use defatted Euglena powder obtained by degreasing Euglena algae bodies, for example, with a non-polar solvent.
（ユーグレナ抽出物）
　本実施形態では、ユーグレナとしてユーグレナ抽出物（ユーグレナエキス）を用いることも可能であり、特にユーグレナ水性溶媒抽出物を用いると好適である。本実施形態において、「ユーグレナ水性溶媒抽出物」とは、水性溶媒を用いてユーグレナから抽出される抽出物を意味し、特に、水性溶媒として水やアルコール類、グリコール類を用い、５℃～６００℃で、数秒～数十時間抽出したユーグレナの水抽出物、熱水抽出物、アルコール抽出物、グリコール抽出物を用いることが好ましい。抽出に使用する水は、必ずしも蒸留水や、純水、又は超純水である必要はなく、例えば、水道水や不純物を含むものであってもよいが、活性成分の抽出を妨げる成分を含まない水が好ましい。 (Euglena extract)
In this embodiment, a Euglena extract (Euglena extract) can be used as Euglena, and it is particularly preferable to use a Euglena aqueous solvent extract. In this embodiment, "Euglena aqueous solvent extract" refers to an extract extracted from Euglena using an aqueous solvent, and it is particularly preferable to use a water extract, hot water extract, alcohol extract, or glycol extract of Euglena extracted using water, alcohols, or glycols as the aqueous solvent at 5°C to 600°C for several seconds to several tens of hours. The water used for extraction does not necessarily have to be distilled water, pure water, or ultrapure water, and may be, for example, tap water or water containing impurities, but water that does not contain components that interfere with the extraction of active ingredients is preferable.
　本実施形態において、「水抽出物」とは、０～５０℃（０℃を除く。）の水による抽出物を意味する。ここで、「水」とは、０～５０℃（０℃を除く。）の水を意味する。水の温度は、活性成分に影響を与えずに、活性成分を十分に抽出できる範囲内であれば特に限定されるものではないが、好ましくは１～４０℃、より好ましくは５～３５℃、特に好ましくは１０～３０℃である。 In this embodiment, "water extract" refers to an extract using water at 0 to 50°C (excluding 0°C). Here, "water" refers to water at 0 to 50°C (excluding 0°C). The temperature of the water is not particularly limited as long as it is within a range in which the active ingredients can be sufficiently extracted without affecting them, but is preferably 1 to 40°C, more preferably 5 to 35°C, and particularly preferably 10 to 30°C.
　本実施形態において、「熱水抽出物」とは、５０℃よりも高い温度の水による抽出物を意味し、「温水抽出物」とも呼ぶことができる。ここで、「熱水」とは、５０℃よりも高温の水を意味し、「熱湯」も含む概念であり、沸騰状態にある水も含まれる。また、液体状態の熱水に限定されることなく、気体状態及び超臨界状態の熱水も含まれる。熱水の温度は、活性成分に影響を与えずに、活性成分を十分に抽出できる範囲内であれば特に限定されるものではないが、好ましくは５０℃より高く１２０℃以下、より好ましくは５０℃より高く１００℃以下である。 In this embodiment, "hot water extract" refers to an extract using water at a temperature higher than 50°C, and can also be called "warm water extract." Here, "hot water" refers to water at a temperature higher than 50°C, and is a concept that includes "hot water," including water in a boiling state. It is also not limited to hot water in a liquid state, but also includes hot water in a gaseous state and a supercritical state. The temperature of the hot water is not particularly limited as long as it is within a range that can sufficiently extract the active ingredients without affecting them, but is preferably higher than 50°C and lower than 120°C, and more preferably higher than 50°C and lower than 100°C.
　抽出に使用する水のｐＨは、活性成分に影響を与えずに、活性成分を十分抽出できる範囲内であれば特に限定されるものではないが、好ましくはｐＨ４～１０、より好ましくはｐＨ５～９、特に好ましくはｐＨ６～８であるとよい。 The pH of the water used for extraction is not particularly limited as long as it is within a range that allows the active ingredients to be sufficiently extracted without affecting them, but a pH of 4 to 10 is preferable, a pH of 5 to 9 is more preferable, and a pH of 6 to 8 is particularly preferable.
　なお、本実施形態では、水性溶媒として、活性成分に影響を与えずに、活性成分を十分抽出できるものであって、通常、抽出に用いることができる溶媒を１種または２種以上選択して用いてもよい。例えば、水、アルコール類、グリコール類などを挙げることができるが、これに限定されるものではない。アルコール類としては、エタノール、メタノール、ｎ－プロパノール、イソプロパノール等が挙げられる。グリコール類としては、ブチレングリコール（ＢＧ）及びプロピレングリコール等が挙げられる。その他の水性溶媒としては、アセトン等が挙げられる。これらの溶媒は単独或いは水溶液として用いても良く、任意の２種または３種以上の混合溶媒として用いてもよい。 In this embodiment, the aqueous solvent can be one that can sufficiently extract the active ingredient without affecting the active ingredient, and one or more solvents that can be normally used for extraction can be selected and used. Examples include water, alcohols, glycols, etc., but are not limited to these. Examples of alcohols include ethanol, methanol, n-propanol, isopropanol, etc. Examples of glycols include butylene glycol (BG) and propylene glycol, etc. Other aqueous solvents include acetone, etc. These solvents can be used alone or as an aqueous solution, or as a mixed solvent of any two or more kinds.
　抽出に用いる水性溶媒の温度は、例えば、０℃以上であり、活性成分に影響を与えないのであれば特に限定されることはない。沸騰状態又は超臨界状態にある水性溶媒を使用することもできるが、５℃～６００℃の水性溶媒を使用するのが好ましく、１０℃～２００℃の水性溶媒を使用するのがより好ましい。したがって、抽出用の水性溶媒とは、沸騰状態や超臨界状態にある水性溶媒も含むものである。抽出に使用する水性溶媒の量は、ユーグレナ中に含まれる水溶性活性成分を十分に溶解することができる量であることが好ましい。 The temperature of the aqueous solvent used for extraction is, for example, 0°C or higher, and is not particularly limited as long as it does not affect the active ingredients. Although an aqueous solvent in a boiling or supercritical state can also be used, it is preferable to use an aqueous solvent at 5°C to 600°C, and it is more preferable to use an aqueous solvent at 10°C to 200°C. Therefore, aqueous solvents for extraction include aqueous solvents in a boiling or supercritical state. The amount of aqueous solvent used for extraction is preferably an amount that can fully dissolve the water-soluble active ingredients contained in Euglena.
　抽出方法も特に限定されず、例えば、以下に示す方法により抽出を行うことができるが、これに限定されることなく、通常の抽出方法を自由に選択して用いることができる。例えば、ユーグレナの藻体乾燥粉末を水性溶媒に所定時間浸漬した後に遠心分離又は濾過する方法、ユーグレナの藻体乾燥粉末を水性溶媒に加えて震盪して均一に分散させた後に遠心分離又は濾過する方法、などが挙げられる。また、抽出を促進するために、ユーグレナを添加後の水性溶媒を加熱することも可能である。 The extraction method is not particularly limited, and for example, extraction can be performed by the method shown below, but ordinary extraction methods can be freely selected and used without being limited thereto. Examples include a method in which dry powder of Euglena algae is soaked in an aqueous solvent for a predetermined time, followed by centrifugation or filtration, and a method in which dry powder of Euglena algae is added to an aqueous solvent, shaken to disperse uniformly, and then centrifuged or filtered. In addition, to promote extraction, it is also possible to heat the aqueous solvent after adding Euglena.
　ユーグレナの水抽出は、以下に示すような通常の方法で行うことができるが、これに限定されるものではない。例えば、ユーグレナ組織及び水を容器に入れ、適宜攪拌又は震盪しながら所定時間静置し、得られた抽出液は、そのまま水抽出物として使用可能である。また、例えば、そのような抽出液を遠心して得られる上清を水抽出物として使用することもできる。また、そのような抽出液又は上清を濃縮、乾燥して水分を除去し、これを水抽出物として使用することもできる。水抽出は、抽出効率を上げて抽出時間を短縮するために、水に、少量、例えば、１０質量％以下のアルコール、好ましくはエタノールを添加して行ってもよい。水抽出を行う場合の抽出時間は、活性成分が抽出される時間であれば特に限定されず、数秒～数十時間の範囲で、抽出の温度に応じて適宜設定することができる。 Water extraction of Euglena can be performed by a conventional method such as those shown below, but is not limited thereto. For example, Euglena tissue and water are placed in a container, and the container is left to stand for a predetermined time while being appropriately stirred or shaken. The obtained extract can be used as it is as a water extract. For example, the supernatant obtained by centrifuging such an extract can also be used as a water extract. The extract or supernatant can also be concentrated and dried to remove water, and used as a water extract. Water extraction can be performed by adding a small amount of alcohol, for example, 10% by mass or less, preferably ethanol, to water in order to increase the extraction efficiency and shorten the extraction time. The extraction time when performing water extraction is not particularly limited as long as it is a time that allows the active ingredient to be extracted, and can be set appropriately in the range of several seconds to several tens of hours depending on the extraction temperature.
　熱水による抽出は、以下に示すような、通常用いられている方法で行なうことができるが、これに限定されるものではない。ユーグレナを、通常用いられる抽出器に水とともに導入した後に、加熱することで抽出を行う。沸騰水または超臨界状態にある水を使用して抽出する場合には、水の蒸気圧に耐え得る抽出器を使用する必要がある。抽出時の圧力は１～５０００気圧に設定することができ、６０～４００気圧に設定するのが好ましい。 　Extraction using hot water can be performed by a commonly used method such as, but not limited to, the following. Euglena is introduced into a commonly used extractor together with water, and then heated to perform extraction. When extracting using boiling water or water in a supercritical state, it is necessary to use an extractor that can withstand the vapor pressure of water. The pressure during extraction can be set to 1 to 5,000 atmospheres, and is preferably set to 60 to 400 atmospheres.
　高温高圧下で抽出を行なう場合には、抽出時間が長過ぎると活性成分が分解したり、化学反応を起こすことがある。従って、高温高圧下で抽出を行なうときには、抽出時間を短時間、例えば、３分以内とするのが好ましく、１分以内とするのがより好ましく、３０秒以内とすることが特に好ましい。 When extraction is performed under high temperature and pressure, if the extraction time is too long, the active ingredients may decompose or undergo a chemical reaction. Therefore, when extraction is performed under high temperature and pressure, it is preferable to keep the extraction time short, for example, within 3 minutes, more preferably within 1 minute, and especially preferably within 30 seconds.
　抽出したユーグレナ抽出物は、そのままでも本実施形態に係る感冒症状の予防及び／又は治療剤の有効成分として用いることができるが、当該抽出物を更に、適当な分離手段（例えば、分配抽出、ゲル濾過法、シリカゲルクロマトグラフィー、逆相若しくは順相の高速液体クロマトグラフィーなど）により活性の高い画分を分画して用いることも可能である。また、ユーグレナ抽出物やその画分を、濃縮、乾燥して水性溶媒を除去し、これを水性溶媒抽出物として使用することもできる。 The extracted Euglena extract can be used as it is as an active ingredient of the agent for preventing and/or treating cold symptoms according to this embodiment, but the extract can also be further fractionated by appropriate separation means (e.g., partition extraction, gel filtration, silica gel chromatography, reverse-phase or normal-phase high-performance liquid chromatography, etc.) to obtain highly active fractions for use. In addition, the Euglena extract or a fraction thereof can be concentrated and dried to remove the aqueous solvent, and used as an aqueous solvent extract.
（加水分解ユーグレナエキス）
　ユーグレナ抽出物として、ユーグレナ属に属する藻類の細胞を蛋白質酵素分解して抽出される水溶性成分、具体的には、ユーグレナ粉末（ユーグレナ藻体）を酵素で加水分解抽出した加水分解ユーグレナエキスを用いても良い。加水分解ユーグレナエキスは、特開２０１０－９００６５号記載の方法に従い、調製することが可能である。 (Hydrolyzed Euglena extract)
The Euglena extract may be a water-soluble component extracted by enzymatic proteolysis of algae cells belonging to the genus Euglena, specifically, a hydrolyzed Euglena extract obtained by enzymatic hydrolysis of Euglena powder (Euglena algae). The hydrolyzed Euglena extract may be prepared according to the method described in JP 2010-90065 A.
　以下、加水分解ユーグレナエキスの調製方法について説明をする。ユーグレナの乾燥体（重量）に対し、好ましくは１００倍量（重量）の精製水を加え、加圧加熱処理を行う。その後、蛋白質分解酵素を添加し藻体を処理する。処理終了後、例えば９０℃で失活し、遠心分離または濾過することにより、残渣と水溶性成分を分離する。 The method for preparing hydrolyzed Euglena extract is explained below. Purified water is added to the dried Euglena (weight), preferably in an amount 100 times (weight), and the mixture is subjected to a pressurized heat treatment. A proteolytic enzyme is then added to treat the algae. After the treatment is complete, the mixture is inactivated, for example, at 90°C, and the residue is separated from the water-soluble components by centrifugation or filtration.
　具体的には、加圧加熱処理条件は、オートクレーブを用いて１００～１５０℃、大気圧～０．２５５ＭＰａ、1分～３０分の加熱加圧処理であることが好ましく、例えば、０．１～０．１４ＭＰａ、１２１℃で１０分間の加熱加圧処理をするとよい。蛋白質分解酵素としては、例えばペプシン、パンクレアチン、パパインなど一般的に用いられるプロテアーゼ活性を有する酵素を単独または併用すればよい特に、ポリペプチド鎖の途中のペプチド結合を加水分解し、幾つかのペプチドに分解するためにエンド型ペプチダーゼを採用することが好ましい。 Specifically, the conditions for the pressurized heat treatment are preferably heating and pressurizing at 100-150°C, atmospheric pressure to 0.255 MPa, and 1-30 minutes using an autoclave, for example, heating and pressurizing at 0.1-0.14 MPa and 121°C for 10 minutes. As the proteolytic enzyme, for example, commonly used enzymes with protease activity such as pepsin, pancreatin, and papain may be used alone or in combination, and it is particularly preferable to use an endopeptidase to hydrolyze peptide bonds in the middle of the polypeptide chain and break it down into several peptides.
　市販の蛋白質分解酵素としては、ヤクルト薬品工業社製のパンチダーゼＭＰ、アロアーゼＡＰ－１０なども採用できる。酵素の添加濃度、反応液のｐＨや反応温度、その他の条件等は、各酵素剤にとって最適な条件を選択すればよい。 Commercially available proteolytic enzymes that can be used include Yakult Pharmaceutical Co., Ltd.'s Panchidase MP and Aroase AP-10. The concentration of the enzyme to be added, the pH of the reaction solution, the reaction temperature, and other conditions can be selected to be optimal for each enzyme preparation.
　このようにして得られた水溶性成分は、そのまま用いることもできるが、本発明の効果を失わない範囲内で分画、脱臭，脱色，濃縮等の精製操作を加えて用いることもできる。 The water-soluble component thus obtained can be used as is, but it can also be used after undergoing purification procedures such as fractionation, deodorization, decolorization, and concentration, within the scope that does not impair the effects of the present invention.
＜パラミロン＞
　「パラミロン（ｐａｒａｍｙｌｏｎ）」とは、約７００個のグルコースがβ－１，３－結合により重合した高分子体（β－１，３－グルカン）で多孔質であり、ユーグレナ属が含有する貯蔵多糖である。パラミロン粒子は、扁平な回転楕円体粒子であり、β－１，３－グルカン鎖がらせん状に絡まりあって形成されている。 <Paramylon>
"Paramylon" is a porous storage polysaccharide contained in the genus Euglena, which is a polymer (β-1,3-glucan) in which approximately 700 glucose molecules are polymerized through β-1,3-bonds. Paramylon particles are flat spheroidal particles formed by entangling β-1,3-glucan chains in a spiral shape.
　パラミロンは、すべての種，変種のユーグレナ細胞内に顆粒として存在し、その個数,形状，粒子の均一性は、種により特徴がある。パラミロンは、グルコースのみからなり、E. gracilis Zの野生株と葉緑体欠損株SM-ZKから得られたパラミロンの平均重合度は、グルコース単位で約７００である。パラミロンは、水，熱水には不溶性であるが、希アルカリ，濃い酸，ジメチルスルホキシド，ホルムアルデヒド，ギ酸に溶ける。パラミロンの平均密度は、E. gracilis Zでは１．５３、E. gracilis var. bacillaris SM-L1では１．６３である。 Paramylon exists as granules in the cells of all species and varieties of Euglena, and the number, shape, and uniformity of the particles vary depending on the species. Paramylon consists only of glucose, and the average degree of polymerization of paramylon obtained from the wild strain of E. gracilis Z and the chloroplast-deficient strain SM-ZK is approximately 700 glucose units. Paramylon is insoluble in water and hot water, but is soluble in dilute alkali, concentrated acid, dimethyl sulfoxide, formaldehyde, and formic acid. The average density of paramylon is 1.53 in E. gracilis Z and 1.63 in E. gracilis var. bacillaris SM-L1.
　パラミロンは、粉末図形法を用いたＸ線解析によれば、３本の直鎖状β－１，３－グルカンが右巻きの縄のようにねじれあったゆるやかならせん構造をとっている。このグルカン分子がいくつか集まってパラミロン顆粒を形成する。パラミロン顆粒は結晶構造部分が非常に多く約９０％を占め、多糖類の中で最も結晶構造率の高い化合物である。なお、パラミロン（（株）ユーグレナ製）の粒度分布は、レーザ回折／散乱式粒度分布測定装置で測定したときのメジアン径が、１．５～２．５μｍである。 According to X-ray analysis using the powder patterning method, paramylon has a loose spiral structure in which three linear β-1,3-glucans are twisted together like a right-handed rope. Several of these glucan molecules come together to form paramylon granules. Paramylon granules have a very high crystalline structure, accounting for approximately 90%, making it the compound with the highest crystalline structure rate among polysaccharides. The particle size distribution of paramylon (manufactured by Euglena Co., Ltd.) has a median diameter of 1.5 to 2.5 μm when measured using a laser diffraction/scattering particle size distribution measuring device.
　パラミロン粒子は、培養されたユーグレナ細胞から任意の適切な方法で単離及び微粒子状に精製され、通常、粉末体として提供されている。例えば、パラミロン粒子は、（１）任意の適切な培地中でのユーグレナ細胞の培養、（２）当該培地からのユーグレナ細胞の分離、（３）分離されたユーグレナ細胞からのパラミロンの単離、（４）単離されたパラミロンの精製、および必要に応じて（５）冷却及びその後の凍結乾燥によって得ることができる。パラミロンの単離は、例えば、大部分が生物分解される種類の非イオン性又は陰イオン性の界面活性剤を用いて行われる。パラミロンの精製は、実質的には単離と同時に行われる。 Paramylon particles are isolated from cultured Euglena cells by any suitable method, purified into fine particles, and usually provided as a powder. For example, paramylon particles can be obtained by (1) culturing Euglena cells in any suitable medium, (2) isolating Euglena cells from the medium, (3) isolating paramylon from the isolated Euglena cells, (4) purifying the isolated paramylon, and, if necessary, (5) cooling and subsequent freeze-drying. Paramylon is isolated, for example, using a nonionic or anionic surfactant of a type that is largely biodegradable. Paramylon is purified substantially simultaneously with the isolation.
（パラミロンの加工品）
　パラミロンの加工品としては、公知の種々の方法によりパラミロンを化学的又は物理的に処理して得た水溶性パラミロン、硫酸化パラミロン等や、パラミロン誘導体も含まれる。 (Paramylon processed products)
Processed paramylon products include water-soluble paramylon obtained by chemically or physically treating paramylon using various known methods, sulfated paramylon, and paramylon derivatives.
　パラミロンの加工品としては、例えば、アモルファスパラミロンやエマルジョンパラミロンが挙げられる。アモルファスパラミロンとは、ユーグレナ由来の結晶性パラミロンをアモルファス化した物質である。アモルファスパラミロンは、ユーグレナから公知の方法で生成された結晶性のパラミロンに対する相対結晶度が、１～２０％である。但し、この相対結晶度は、特開２０１１－１８４５９２号記載の方法により求めたものである。 Processed paramylon products include, for example, amorphous paramylon and emulsion paramylon. Amorphous paramylon is a substance in which crystalline paramylon derived from Euglena has been made amorphous. Amorphous paramylon has a relative crystallinity of 1-20% compared to crystalline paramylon produced from Euglena by known methods. However, this relative crystallinity was determined by the method described in JP 2011-184592 A.
　つまり、アモルファスパラミロン及びパラミロンを、それぞれ、粉砕機（Ｒｅｔｓｈ社製ボールミルＭＭ４００）にて、振動数２０回／秒で５分間粉砕後、Ｘ線回折装置（スペクトリス社製Ｈ‘ＰｅｒｔＰＲＯ）を用い、管電圧４５ＫＶ、管電流４０ｍＡにて、２θが５°乃至３０°の範囲でスキャンを行い、パラミロンとアモルファスパラミロンの２θ＝２０°の付近の回折ピークＰｃ，Ｐａを得る。このＰｃ，Ｐａの値を用い、アモルファスパラミロンの相対結晶度を、アモルファスパラミロンの相対結晶度＝Ｐａ／Ｐｃ×１００（％）により算出する。 In other words, amorphous paramylon and paramylon are each ground in a grinder (Retsh ball mill MM400) at a frequency of 20 revolutions per second for 5 minutes, and then an X-ray diffraction device (Spectris H'PertPRO) is used to scan in the 2θ range of 5° to 30° at a tube voltage of 45 KV and a tube current of 40 mA to obtain the diffraction peaks Pc and Pa of paramylon and amorphous paramylon near 2θ = 20°. Using these Pc and Pa values, the relative crystallinity of amorphous paramylon is calculated from the formula: Relative crystallinity of amorphous paramylon = Pa/Pc x 100 (%).
　アモルファスパラミロンは、特開２０１１－１８４５９２号記載の方法に従い、結晶性のパラミロン粉末を、アルカリ処理した後に酸で中和し、その後洗浄、水分除去工程を経て、乾燥を行うことにより調製される。パラミロンの加工品としては、そのほか、公知の種々の方法によりパラミロンを化学的又は物理的に処理して得た水溶性パラミロン、硫酸化パラミロン等や、パラミロン誘導体も含まれる。 Amorphous paramylon is prepared according to the method described in JP 2011-184592 A by treating crystalline paramylon powder with an alkali, neutralizing it with acid, washing, removing moisture, and then drying. Paramylon processed products also include water-soluble paramylon, obtained by chemically or physically processing paramylon using various known methods, sulfated paramylon, and paramylon derivatives.
　「エマルジョンパラミロン」とは、その加工方法及び物性が乳化物に類似していることから、エマルジョンパラミロンとも呼ばれる物質であって、特開２０１６－１９９６５０号記載の方法に従い、パラミロンに水を加えて得た流体を超高圧で細孔ノズルから噴出させて被衝突物に衝突させる衝突処理を行うことにより得られ、４倍以上の水と結合して膨潤した加工パラミロンである。 "Emulsion paramylon" is a substance also known as emulsion paramylon because its processing method and physical properties are similar to those of an emulsion. It is obtained by adding water to paramylon and carrying out a collision process in which the resulting fluid is ejected from a fine nozzle at ultra-high pressure and collided with an object to be impacted, according to the method described in JP 2016-199650 A, and is processed paramylon that has combined with more than four times its amount of water and swelled.
　エマルジョンパラミロンは、粉体等の固体に水溶性溶媒を加えたスラリーを、細孔ノズルから超高圧で噴出させて被衝突物に衝突させる公知の物性改質装置（例えば、特開２０１１－８８１０８号公報、特開平６－４７２６４号公報記載の装置）で、噴出時のノズル圧力２４５ＭＰａで、１回以上衝突処理を行うことにより得ることができる。 Emulsion paramylon can be obtained by performing a collision process at least once using a known property modification device (such as the device described in JP 2011-88108 A and JP 6-47264 A) in which a slurry of a powder or other solid with a water-soluble solvent is sprayed at ultra-high pressure from a fine nozzle and collided with a collision target, with a nozzle pressure of 245 MPa during spraying.
　エマルジョンパラミロンは、レーザ回折／散乱式粒度分布測定装置で粒度を測定したときのメジアン径が、パラミロンの５倍以上であり、７μｍ以上であって、光学電子顕微鏡により、粒子が、隣接する粒子と付着していることが観察され、パラミロンに対して４倍以上の水と結合して膨潤している。 When the particle size of emulsion paramylon is measured using a laser diffraction/scattering particle size distribution analyzer, the median diameter is more than 7 μm, which is more than five times that of paramylon, and when observed using an optical electron microscope, the particles are observed to be attached to adjacent particles, and they swell by combining with more than four times as much water as paramylon.
　原料パラミロンと水を混合したスラリーは、さらさらした流体であるが、エマルジョンパラミロンは、パラミロンが水分子中に分散して、粘度が増加して粘性を有し、触ったときに手に付着するような粘着性と、弾力性を有し、糊のような触感を備えている。なお、その処理方法と物性から、得られた加工パラミロンを本明細書においてエマルジョンパラミロンと呼んでいるが、エマルジョン化しているか否かは不明であり、パラミロンが水と結合して膨潤している状態である。 The slurry made by mixing raw paramylon with water is a smooth fluid, but in emulsion paramylon, the paramylon disperses in the water molecules, increasing its viscosity and giving it a sticky, elastic texture that sticks to your hand when you touch it, like glue. In this specification, the processed paramylon obtained is called emulsion paramylon based on its processing method and physical properties, but it is unclear whether it is emulsified or not, and the paramylon is in a swollen state due to binding with water.
＜用途＞
　本実施形態に係る感冒症状の予防及び／又は治療剤は、経口組成物、例えば、健康食品等の食品組成物又は医薬品組成物として構成され、感冒症状を予防及び／又は治療するために、予防的及び／又は治療的に使用・摂取・投与される。ユーグレナ由来物質は、食品としても摂取可能で副作用がないため、継続的に使用・摂取・投与可能である。 <Applications>
The preventive and/or therapeutic agent for cold symptoms according to this embodiment is configured as an oral composition, for example, a food composition such as a health food or a pharmaceutical composition, and is used, ingested, or administered prophylactically and/or therapeutically to prevent and/or treat cold symptoms. The Euglena-derived substance can be ingested as a food and has no side effects, so it can be used, ingested, or administered continuously.
（食品組成物）
　本実施形態の感冒症状の予防及び／又は治療剤は、食品の分野では、感冒症状の予防作用及び／又は治療作用を有効に発揮できる有効な量のユーグレナ由来物質を食品素材として、各種食品に配合することにより、当該作用を有する食品組成物を提供することができる。すなわち、本発明は、食品の分野において、抗老化用等と表示された食品の食品組成物を提供することができる。当該食品組成物としては、一般の食品のほか、特定保健用食品、栄養機能食品、機能性表示食品、病院患者用食品、サプリメント等が挙げられる。また、食品添加物として用いることもできる。 (Food composition)
In the field of food, the agent for preventing and/or treating cold symptoms of this embodiment can provide a food composition having said effect by blending an effective amount of a Euglena-derived substance capable of effectively exerting a preventive and/or therapeutic effect on cold symptoms as a food ingredient into various foods. That is, in the field of food, the present invention can provide a food composition of a food labeled for anti-aging or the like. Examples of such food compositions include general foods, foods for specified health uses, foods with nutrient functions, foods with functional claims, foods for hospital patients, supplements, and the like. The food composition can also be used as a food additive.
　当該食品組成物としては、例えば、調味料、畜肉加工品、農産加工品、飲料（乳酸菌飲料、清涼飲料、アルコール飲料、炭酸飲料、乳飲料、果汁飲料、茶、コーヒー、栄養ドリンク等）、粉末飲料（粉末ジュース、粉末スープ等）、濃縮飲料、菓子類（キャンディ（のど飴）、クッキー、ビスケット、ガム、グミ、チュアブル、タブレット剤、チョコレート等）、パン、シリアル等が挙げられる。また、特定保健用食品、栄養機能食品、機能性表示食品等の場合、カプセル、トローチ、シロップ、顆粒、粉末等の形状であっても良い。 Examples of such food compositions include seasonings, processed meat products, processed agricultural products, beverages (lactic acid bacteria beverages, soft drinks, alcoholic beverages, carbonated beverages, dairy beverages, fruit juice beverages, tea, coffee, nutritional drinks, etc.), powdered beverages (powdered juice, powdered soup, etc.), concentrated beverages, confectioneries (candy (throat lozenges), cookies, biscuits, gum, gummies, chewables, tablets, chocolate, etc.), bread, cereals, etc. In addition, in the case of foods for specified health uses, foods with nutritional functions, foods with functional claims, etc., the foods may be in the form of capsules, lozenges, syrup, granules, powder, etc.
　ここで特定保健用食品とは、生理学的機能等に影響を与える保健機能成分を含む食品であって、消費者庁長官の許可を得て特定の保健の用途に適する旨を表示可能なものである。本発明においては、抗老化に関する特定の保健用途を表示して販売される食品となる。 Here, a "specified health food" is a food that contains functional ingredients that affect physiological functions, etc., and can be labeled as suitable for a specific health purpose with the permission of the Commissioner of the Consumer Affairs Agency. In the present invention, it is a food that is sold with a label indicating a specific health purpose related to anti-aging.
　また栄養機能食品とは、栄養成分（ビタミン、ミネラル）の補給のために利用される食品であって、栄養成分の機能を表示するものである。栄養機能食品として販売するためには、一日当たりの摂取目安量に含まれる栄養成分量が定められた上限値、下限値の範囲内にある必要があり、栄養機能表示だけでなく注意喚起表示等もする必要がある。 Foods with nutrient functions are foods that are used to supplement nutritional components (vitamins, minerals) and display the function of the nutritional components. To be sold as such, the amount of nutritional components contained in the recommended daily intake must be within the range of set upper and lower limits, and in addition to displaying the nutritional functions, warning labels must also be included.
　また機能性表示食品とは、事業者の責任において、科学的根拠に基づいた機能性を表示した食品である。販売前に安全性及び機能性の根拠に関する情報などが消費者庁長官へ届け出られたものである。 Foods with functional claims are foods that display functionality based on scientific evidence at the responsibility of the business operator. Information on safety and the basis for functionality is submitted to the Commissioner of the Consumer Affairs Agency before sale.
　本実施形態に係る食品組成物には、ユーグレナ由来物質に加え、通常食品組成物に用いることができる成分を、１種または２種以上自由に選択して配合することが可能である。例えば、各種調味料、保存剤、乳化剤、安定剤、香料、着色剤、防腐剤、ｐＨ調整剤などの、食品分野で通常使用し得る全ての添加剤を含有させることができる。 In addition to the Euglena-derived substances, the food composition according to this embodiment can contain one or more freely selected ingredients that can be used in regular food compositions. For example, all additives that can be used regularly in the food industry, such as various seasonings, preservatives, emulsifiers, stabilizers, flavorings, colorants, preservatives, and pH adjusters, can be included.
（医薬品組成物）
　本実施形態の感冒症状の予防及び／又は治療剤は、医薬の分野では、感冒症状の予防作用及び／又は治療作用を有効に発揮できる量のユーグレナ由来物質と共に、薬学的に許容される担体や添加剤を配合することにより、当該作用を有する医薬品組成物が提供される。当該医薬品組成物は、医薬品であっても医薬部外品であってもよい。 Pharmaceutical Compositions
In the field of medicine, the agent for preventing and/or treating cold symptoms of this embodiment is a pharmaceutical composition having said effect, which can be provided by combining an amount of a Euglena-derived substance capable of effectively exerting an effect of preventing and/or treating cold symptoms with pharma- ceutical carriers and additives. The pharmaceutical composition may be a drug or a quasi-drug.
　当該医薬品組成物は、内用的（特に経口的）に適用されることが好適であるが、外用的に適用されても良い。従って、当該医薬品組成物は、内服剤、静脈注射、皮下注射、皮内注射、筋肉注射及び／又は腹腔内注射等の注射剤、経粘膜適用剤、経皮適用剤等の製剤形態で使用することができる。当該医薬品組成物の剤型としては、適用の形態により、適当に設定できるが、例えば、錠剤、顆粒剤、カプセル剤、粉末剤、散剤などの固形製剤、液剤、懸濁剤などの液状製剤、軟膏剤、またはゲル剤等の半固形剤が挙げられる。 The pharmaceutical composition is preferably applied internally (particularly orally), but may also be applied externally. Therefore, the pharmaceutical composition can be used in the form of an oral preparation, an injection such as an intravenous injection, a subcutaneous injection, an intradermal injection, an intramuscular injection and/or an intraperitoneal injection, a transmucosal application preparation, a transdermal application preparation, etc. The dosage form of the pharmaceutical composition can be appropriately set depending on the form of application, and examples include solid preparations such as tablets, granules, capsules, powders, and dustings, liquid preparations such as solutions and suspensions, semi-solid preparations such as ointments or gels.
　本実施形態に係る医薬品組成物には、薬学的に許容される添加剤を１種または２種以上自由に選択して含有させることができる。例えば、本実施形態に係る医薬品組成物を経口剤に適用させる場合、例えば、賦形剤、結合剤、崩壊剤、界面活性剤、保存剤、着色剤、矯味剤、香料、安定化剤、防腐剤、酸化防止剤等の、医薬製剤の分野で通常使用し得る全ての添加剤を含有させることができる。また、ドラックデリバリーシステム（ＤＤＳ）を利用して、徐放性製剤等にすることもできる。 The pharmaceutical composition according to this embodiment can contain one or more pharma- ceutically acceptable additives of your choice. For example, when the pharmaceutical composition according to this embodiment is applied to an oral preparation, it can contain all additives that are typically used in the field of pharmaceutical preparations, such as excipients, binders, disintegrants, surfactants, preservatives, colorants, flavorings, fragrances, stabilizers, preservatives, antioxidants, etc. In addition, it can also be made into a sustained-release preparation by utilizing a drug delivery system (DDS).
＜用法・用量＞
　本実施形態の感冒症状の予防及び／又は治療剤、感冒症状の予防及び／又は改善用食品組成物の用法としては、例えば、カプセル剤、粉末剤、錠剤、顆粒、液剤又はシロップ等によって経口投与すると良い。本実施形態の感冒症状の予防及び／又は治療剤、感冒症状の予防及び／又は改善用食品組成物の投与量や投与形態は、対象、病態やその進行状況、その他の条件によって適宜選択すればよい。 <Dosage and Administration>
The method of use of the preventive and/or therapeutic agent for cold symptoms and the food composition for preventing and/or improving cold symptoms of this embodiment may be, for example, orally administered in the form of capsules, powders, tablets, granules, liquids, syrups, etc. The dosage and administration form of the preventive and/or therapeutic agent for cold symptoms and the food composition for preventing and/or improving cold symptoms of this embodiment may be appropriately selected depending on the subject, the disease state and its progression, and other conditions.
　例えば、ヒト（成人）を対象に感冒症状の予防作用及び／又は治療作用を得ることを目的として経口投与する場合には、一般に、ユーグレナ由来物質として、例えば、ユーグレナを乾燥重量で１日当たり１０～５０００ｍｇ、好ましくは５００～５０００ｍｇ、さらに好ましくは１０００～５０００ｍｇ程度の用量で投与するとよい。 For example, when orally administering to humans (adults) for the purpose of preventing and/or treating cold symptoms, the Euglena-derived substance is generally administered at a dose of 10 to 5,000 mg, preferably 500 to 5,000 mg, and more preferably 1,000 to 5,000 mg of Euglena per day in dry weight.
　投与（服用）の頻度は、好ましくは１週間に数回、２日に１回、１日１回、またはそれ以上であり、より好ましくは１日２回以上であり、さらに好ましくは１日３回であり、これを、好ましくは朝、昼、晩、具体的には毎食後（朝食後、昼食後、夕食後）に投与する。 The frequency of administration (taking the medicine) is preferably several times a week, once every two days, once a day, or more, more preferably two or more times a day, and even more preferably three times a day, preferably in the morning, midday, and evening, specifically after each meal (after breakfast, lunch, and dinner).
　投与（服用）の期間は、長期的または持続的に服用することが望ましく、例えば５週間以上、好ましくは８週間以上である。 The administration (taking of the drug) should be long-term or sustained, for example, for a period of 5 weeks or more, preferably 8 weeks or more.
　例えば、ユーグレナ由来物質として、ユーグレナ藻体が１日あたり５００ｍｇ以上で５週間以上継続して摂取されると好適である。 For example, it is preferable to ingest 500 mg or more of Euglena algae as a Euglena-derived substance per day for at least five weeks.
　以下、具体的実施例に基づいて本発明を具体的に説明するが、本発明はこれらに限定されるものではない。 The present invention will be described in detail below based on specific examples, but the present invention is not limited to these.
＜試験食品組成物について＞
　実施例１（被験食品群）及び比較例１（プラセボ群）の試験食品組成物の組成を以下の表１及び表２に示す。ユーグレナとして、ユーグレナ・グラシリス粉末（ユーグレナ藻体、（株）ユーグレナ製）を用いた。 <Test food composition>
The compositions of the test food compositions of Example 1 (test food group) and Comparative Example 1 (placebo group) are shown in the following Tables 1 and 2. Euglena gracilis powder (Euglena algae, manufactured by Euglena Co., Ltd.) was used as Euglena.
Figure JPOXMLDOC01-appb-T000001
Figure JPOXMLDOC01-appb-T000001
　試験食品組成物の剤形はハードカプセルであり、包装はアルミパウチ包であった。包装開封後は、冷蔵庫に保管した。 The test food composition was in the form of a hard capsule and packaged in an aluminum pouch. After opening the package, it was stored in the refrigerator.
＜試験：ユーグレナの摂取が感冒症状の発生に及ぼす影響＞
　２０代～８０代の男女を対象にして、８週間ユーグレナ１，０００ｍｇ／日含有カプセル（被験食品群）又はプラセボカプセル（プラセボ群）の摂取を継続し、毎日の感冒症状の有無を記録した。 <Test: Effect of Euglena intake on the occurrence of cold symptoms>
Men and women in their 20s to 80s were asked to continue taking capsules containing 1,000 mg of Euglena per day (test food group) or placebo capsules (placebo group) for eight weeks, and the presence or absence of cold symptoms was recorded daily.
　試験参加に同意した３５６例のうち、適格基準を満たした２２０例を本試験に組入れ、被験食品群とプラセボ群に１１０例ずつ割り付けた。全員が割り付けられた介入の提供を受けたが、摂取８週間後検査に来院しなかった症例が７例（プラセボ群に３例、被験食品群に４例）確認された。ＦＡＳおよびＳＡＦでは、いずれも割り付け後に介入を一度も受けていない症例７例（プラセボ群に３例、被験食品群に４例）が除外された。よって、解析データセットの症例数はいずれも２１３例（プラセボ群に１０７例、被験食品群に１０６例）であった。 Of the 356 subjects who agreed to participate in the study, 220 who met the eligibility criteria were enrolled in the study, with 110 subjects each being assigned to the test food group and the placebo group. All subjects received the intervention to which they were assigned, but seven subjects (three in the placebo group and four in the test food group) were identified as not attending the hospital for testing eight weeks after ingestion. In both the FAS and SAF, seven subjects (three in the placebo group and four in the test food group) who never received the intervention after allocation were excluded. Therefore, the number of subjects in the analysis dataset was 213 for both cases (107 in the placebo group and 106 in the test food group).
　試験は二重盲検法で行った。感冒症状は、１．「全身倦怠感」、２．「寒気」、３．「熱っぽさ」、４．「疲労」、５．「くしゃみ」、６．「鼻汁」、７．「鼻閉」、８．「のどの痛み」、９．「せき」、１０．「関節痛」、１１．「筋肉痛」、１２．「頭痛」について、１～５の５段階で回答し（１．「全くない」、２．「ほとんどない」、３．「少しだけある」、４．「多少はある」、５．「ひどい」）、３～５のいずれかを回答した場合を発症ありと判定し、摂取期間中における各症状の累積発症日数および最大持続日数を記録した。 The test was a double-blind study. Participants were asked to answer questions about cold symptoms, including 1. "general malaise," 2. "chills," 3. "feeling feverish," 4. "fatigue," 5. "sneezing," 6. "runny nose," 7. "nasal congestion," 8. "sore throat," 9. "cough," 10. "joint pain," 11. "muscle pain," and 12. "headache," on a five-point scale from 1 to 5 (1. "not at all," 2. "hardly any," 3. "a little," 4. "somewhat," 5. "severe"). Participants were judged to have developed symptoms if they answered 3 to 5, and the cumulative number of days each symptom developed and the maximum duration during the intake period were recorded.
　また、全身倦怠感、寒気、熱っぽさ、疲労、くしゃみ、鼻汁、鼻閉、のどの痛み、せき、関節痛、筋肉痛、頭痛のいずれかが１つ以上あった場合を感冒症状、１と回答した日の２日目以降に１、２以外の回答をした日を当該症状または感冒症状の発症日（摂取開始１日目または２日目に１、２以外の回答を行った場合は、当該日も発症日に含む）と定義し、感冒症状の累積日数および最大持続日数、重症度、症例数、発症日の累積日数等を記録した。 In addition, the presence of one or more of the following symptoms was defined as cold symptoms: general malaise, chills, fever, fatigue, sneezing, runny nose, nasal congestion, sore throat, cough, joint pain, muscle pain, or headache. The day on which a response other than 1 or 2 was given on or after the second day after response 1 was defined as the onset date of said symptom or cold symptoms (if a response other than 1 or 2 was given on the first or second day after starting intake, that day was also included in the onset date). The cumulative number of days with cold symptoms, maximum duration, severity, number of cases, cumulative number of days with onset, etc. were recorded.
　集計は摂取開始日から摂取７日目までを期間Ｉ、８日目から１４日目を期間ＩＩ、以降１週間おきに期間を定め、最後の１週間（摂取５０日目から摂取５６日目）を期間ＶＩＩＩとする。 The period from the start of intake to the 7th day of intake will be Period I, the period from the 8th to the 14th day will be Period II, and thereafter each subsequent period will be determined as one week apart, with the final week (from the 50th to the 56th day of intake) being Period VIII.
　摂取開始前５日間において、２群間の感冒症状の累積日数や重症度には群間の差異はなかった。 In the five days prior to the start of intake, there were no differences between the two groups in the cumulative number of days with cold symptoms or their severity.
＜結果＞
　図１に示されるように、８週間における感冒症状累積日数（平均）について、ユーグレナ摂取群でプラセボ摂取群と比較して有意に少なくなった。 <Results>
As shown in FIG. 1, the cumulative number of days with cold symptoms (average) over the 8-week period was significantly shorter in the Euglena intake group than in the placebo intake group.
　図３Ａに示されるように、５週目～８週目における感冒症状累積日数（平均）について、ユーグレナ摂取群でプラセボ摂取群と比較して有意に少なくなった。より詳細には、図２Ａ～２Ｅに示されるように、ユーグレナ摂取群でプラセボ摂取群と比較して、全期間（８週間）の熱っぽさ、疲労の重症度平均値が有意に低くなり、後期（後半４週間）の鼻閉、のどの痛み、筋肉痛の重症度平均値が有意に低くなった。 As shown in Figure 3A, the cumulative number of days with cold symptoms (average) from weeks 5 to 8 was significantly less in the Euglena intake group than in the placebo intake group. More specifically, as shown in Figures 2A to 2E, the average severity of feverishness and fatigue over the entire period (8 weeks) was significantly lower in the Euglena intake group than in the placebo intake group, and the average severity of nasal congestion, sore throat, and muscle pain in the later period (last 4 weeks) was significantly lower.
　ユーグレナ摂取群では、感冒症状の中でも、とくに熱っぽさ、疲労の重症度が減った。また、ユーグレナ摂取群では、後期（後半４週間、５週目～８週目）においては、鼻閉、のどの痛み、筋肉痛の重症度が減った。また、ユーグレナ摂取群では、後期における疲労の累積日数（平均）が有意に少なくなった（図３Ｂ）。 In the Euglena intake group, the severity of cold symptoms, especially fever and fatigue, was reduced. In addition, in the Euglena intake group, the severity of nasal congestion, sore throat, and muscle pain was reduced in the later stages (last 4 weeks, weeks 5 to 8). Furthermore, in the Euglena intake group, the cumulative number of days of fatigue in the later stages (average) was significantly shorter (Figure 3B).
　図４Ａ～４Ｇに示されるように、８週間における感冒症状、その中でも疲労、くしゃみ、鼻汁、鼻閉、のどの痛み、せき、筋肉痛の累積日数がユーグレナ摂取群でプラセボ摂取群と比較して有意に少なくなった。 As shown in Figures 4A to 4G, the cumulative number of days with cold symptoms over an 8-week period, including fatigue, sneezing, runny nose, nasal congestion, sore throat, cough, and muscle pain, was significantly less in the Euglena intake group than in the placebo intake group.
　図５Ａ～５Ｅに示されるように、疲労、くしゃみ、鼻閉、せき、筋肉痛に関して、１．「全くない」と回答した被験者の８週間の累積数が有意に増加し、２．「ほとんどない」、３．「少しだけある」、４．「多少はある」、５．「ひどい」と回答した被験者の累積数が有意に減少した。 As shown in Figures 5A to 5E, regarding fatigue, sneezing, nasal congestion, coughing, and muscle pain, the cumulative number of subjects who answered 1. "not at all" significantly increased over the 8-week period, while the cumulative number of subjects who answered 2. "hardly any," 3. "a little," 4. "somewhat," and 5. "severe" significantly decreased.
（試験参加者ごとの感冒症状の累積日数・最大持続日数・重症度・発症回数）
　累積日数・最大持続日数・重症度・発症回数において、有意差が認められた項目の、期間、ＭｅａｎとＳＤ、群間差とその９５％ＣＩ－、９５％ＣＩ＋、有意確率を示した。 (Cumulative number of days with cold symptoms, maximum duration, severity, and number of episodes for each study participant)
For items in which significant differences were observed, such as cumulative number of days, maximum duration of symptoms, severity, and number of episodes, the duration, mean and SD, intergroup differences and their 95% CI-, 95% CI+, and significance probability are shown.
（１）感冒症状の累積日数
　有意差が認められた期間のうち、被験食品群でプラセボ群よりも低値を示した期間は、全期間（プラセボ群：２１．３±１９．２日、被験食品群：１５．９±１７．５日、群間差：－５．４日［－１０．４、－０．５］、Ｐ＝０．０３２）、後期（プラセボ群：１１．０±１０．４日、被験食品群：７．７±９．３日、群間差：－３．３日［－６．０、－０．７］、Ｐ＝０．０１５）であった。 (1) Cumulative number of days with cold symptoms Among the periods in which significant differences were observed, the periods in which the test food group showed lower values than the placebo group were the entire period (placebo group: 21.3 ± 19.2 days, test food group: 15.9 ± 17.5 days, difference between groups: -5.4 days [-10.4, -0.5], P = 0.032) and the late period (placebo group: 11.0 ± 10.4 days, test food group: 7.7 ± 9.3 days, difference between groups: -3.3 days [-6.0, -0.7], P = 0.015).
（２）疲労の累積日数
　有意差が認められた期間のうち、被験食品群でプラセボ群よりも低値を示した期間は、後期（プラセボ群：６．８±８．８日、被験食品群：４．５±７．５日、群間差：－２．３日［－４．５、－０．１］、Ｐ＝０．０４２）であった。 (2) Cumulative number of days of fatigue Among the periods in which a significant difference was observed, the period in which the test food group showed lower values than the placebo group was the late period (placebo group: 6.8 ± 8.8 days, test food group: 4.5 ± 7.5 days, difference between groups: -2.3 days [-4.5, -0.1], P = 0.042).
（３）熱っぽさの重症度
　有意差が認められた期間のうち、被験食品群でプラセボ群よりも低値を示した期間は、全期間　（プラセボ群：１．１±０．３、被験食品群：１．０±０．２、群間差：－０．１［－０．２、０．０］、Ｐ＝０．０４０）であった。 (3) Severity of feverishness Among the periods in which significant differences were observed, the test food group showed lower values than the placebo group throughout the entire period (placebo group: 1.1 ± 0.3, test food group: 1.0 ± 0.2, difference between groups: -0.1 [-0.2, 0.0], P = 0.040).
（４）疲労の重症度
　有意差が認められた期間のうち、被験食品群でプラセボ群よりも低値を示した期間は、後期（プラセボ群：１．８±０．９、被験食品群：１．５±０．７、群間差：－０．３［－０．５、－０．１］、Ｐ＝０．００７）であった。 (4) Severity of fatigue Among the periods in which significant differences were observed, the period in which the test food group showed lower values than the placebo group was the later period (placebo group: 1.8 ± 0.9, test food group: 1.5 ± 0.7; difference between groups: -0.3 [-0.5, -0.1], P = 0.007).
（５）鼻閉の重症度
　有意差が認められた期間のうち、被験食品群でプラセボ群よりも低値を示した期間は、後期（プラセボ群：１．３±０．６、被験食品群：１．１±０．４、群間差：－０．１［－０．３、０．０］、Ｐ＝０．０２９）であった。 (5) Severity of nasal congestion Among the periods in which significant differences were observed, the period in which the test food group showed lower values than the placebo group was the late period (placebo group: 1.3 ± 0.6, test food group: 1.1 ± 0.4, difference between groups: -0.1 [-0.3, 0.0], P = 0.029).
（６）のどの痛みの重症度
　有意差が認められた期間のうち、被験食品群でプラセボ群よりも低値を示した期間は、後期（プラセボ群：１．２±０．５、被験食品群：１．１±０．３、群間差：－０．１［－０．２、０．０］、Ｐ＝０．０２３）であった。 (6) Severity of sore throat Among the periods in which a significant difference was observed, the period in which the test food group showed lower values than the placebo group was the later period (placebo group: 1.2 ± 0.5, test food group: 1.1 ± 0.3, difference between groups: -0.1 [-0.2, 0.0], P = 0.023).
（７）筋肉痛の重症度
　有意差が認められた期間のうち、被験食品群でプラセボ群よりも低値を示した期間は、後期（プラセボ群：１．２±０．５、被験食品群：１．１±０．４、群間差：－０．１［－０．３、０．０］、Ｐ＝０．０３６）であった。 (7) Severity of muscle pain Among the periods in which significant differences were observed, the period in which the test food group showed lower values than the placebo group was the later period (placebo group: 1.2 ± 0.5, test food group: 1.1 ± 0.4, difference between groups: -0.1 [-0.3, 0.0], P = 0.036).
（８）のどの痛みの発症回数
　有意差が認められた期間のうち、被験食品群でプラセボ群よりも低値を示した期間は、全期間（プラセボ群：２．０±２．７回、被験食品群：１．０±２．２回、群間差：－０．９回［－１．６、－０．３］、Ｐ＝０．００７）、前期（プラセボ群：１．１±１．７回、被験食品群：０．６±１．３回、群間差：－０．５回［－０．９、－０．１］、Ｐ＝０．０１３）、後期（プラセボ群：０．８±１．３回、被験食品群：０．４±１．０回、群間差：－０．４回［－０．７、－０．１］、Ｐ＝０．０１５）であった。 (8) Number of episodes of sore throat Among the periods in which significant differences were observed, the periods in which the test food group showed lower values than the placebo group were the entire period (placebo group: 2.0 ± 2.7 times, test food group: 1.0 ± 2.2 times, difference between groups: -0.9 times [-1.6, -0.3], P = 0.007), the early period (placebo group: 1.1 ± 1.7 times, test food group: 0.6 ± 1.3 times, difference between groups: -0.5 times [-0.9, -0.1], P = 0.013), and the late period (placebo group: 0.8 ± 1.3 times, test food group: 0.4 ± 1.0 times, difference between groups: -0.4 times [-0.7, -0.1], P = 0.015).
（９）関節痛の発症回数
　有意差が認められた期間のうち、被験食品群でプラセボ群よりも低値を示した期間は、全期間（プラセボ群：１．５±２．５回、被験食品群：０．９±１．７回、群間差：－０．６回［－１．２、－０．１］、Ｐ＝０．０２８）、後期（プラセボ群：０．７±１．４回、被験食品群：０．４±１．０回、群間差：－０．３回［－０．７、０．０］、Ｐ＝０．０４０）であった。 (9) Number of episodes of joint pain Among the periods in which significant differences were observed, the periods in which the test food group showed lower values than the placebo group were the entire period (placebo group: 1.5 ± 2.5 times, test food group: 0.9 ± 1.7 times, difference between groups: -0.6 times [-1.2, -0.1], P = 0.028) and the late period (placebo group: 0.7 ± 1.4 times, test food group: 0.4 ± 1.0 times, difference between groups: -0.3 times [-0.7, 0.0], P = 0.040).
（１０）筋肉痛の発症回数
　有意差が認められた期間のうち、被験食品群でプラセボ群よりも低値を示した期間は、全期間（プラセボ群：２．０±２．４回、被験食品群：１．３±２．２回、群間差：－０．７回［－１．３、０．０］、Ｐ＝０．０３６）であった。 (10) Number of episodes of muscle pain Among the periods in which a significant difference was observed, the test food group showed lower values than the placebo group over the entire period (placebo group: 2.0 ± 2.4 times, test food group: 1.3 ± 2.2 times, difference between groups: -0.7 times [-1.3, 0.0], P = 0.036).
（各感冒症状を発症した症例数）
　感冒症状を発症した症例数において、有意差が認められた項目の、期間、発症率、群間差とその９５％ＣＩ－、９５％ＣＩ＋、有意確率を示した。 (Number of cases with each cold symptom)
For items in which significant differences were found in the number of cases that developed cold symptoms, the duration, incidence rate, intergroup differences, their 95% CI-, 95% CI+, and significance probability are shown.
（１）疲労を発症した症例数
　有意差が認められた期間のうち、被験食品群でプラセボ群よりも低値を示した期間は、後期（プラセボ群：６６．４％、被験食品群：５１．９％、群間差：－１４．５％［－２７．７、－１．３］、Ｐ＝０．０３７）であった。 (1) Number of cases who developed fatigue Among the periods in which significant differences were observed, the period in which the test food group showed lower values than the placebo group was the later period (placebo group: 66.4%, test food group: 51.9%, difference between groups: -14.5% [-27.7, -1.3], P = 0.037).
（２）鼻閉を発症した症例数
　有意差が認められた期間のうち、被験食品群でプラセボ群よりも低値を示した期間は、後期（プラセボ群：２３．４％、被験食品群：１２．３％、群間差：－１１．１％［－２１．４、－０．８］、Ｐ＝０．０４８）であった。 (2) Number of cases who developed nasal congestion Among the periods in which significant differences were observed, the period in which the test food group showed lower values than the placebo group was the later period (placebo group: 23.4%, test food group: 12.3%, difference between groups: -11.1% [-21.4, -0.8], P = 0.048).
（３）筋肉痛を発症した症例数
　有意差が認められた期間のうち、被験食品群でプラセボ群よりも低値を示した期間は、後期（プラセボ群：２９．０％、被験食品群：１５．１％、群間差：－１３．９％［－２５．０、－２．７］、Ｐ＝０．０２０）であった。 (3) Number of cases that developed muscle pain Among the periods in which significant differences were observed, the period in which the test food group showed lower values than the placebo group was the later period (placebo group: 29.0%, test food group: 15.1%, difference between groups: -13.9% [-25.0, -2.7], P = 0.020).
（４）頭痛を発症した症例数
　有意差が認められた期間のうち、被験食品群でプラセボ群よりも低値を示した期間は、後期（プラセボ群：４３．０％、被験食品群：２８．３％、群間差：－１４．７％［－２７．６、－１．８］、Ｐ＝０．０３２）であった。 (4) Number of cases that developed headaches Among the periods in which significant differences were observed, the period in which the test food group showed lower values than the placebo group was the late period (placebo group: 43.0%, test food group: 28.3%, difference between groups: -14.7% [-27.6, -1.8], P = 0.032).
（群ごとの感冒症状の累積日数・各回答（重症度）の割合）
　累積日数、各回答の割合において、有意差が認められた項目のみ、期間、該当率、群間差とその９５％ＣＩ－、９５％ＣＩ＋、有意確率を示した。 (Cumulative number of days with cold symptoms and percentage of each response (severity) by group)
Only for items where significant differences were found in the cumulative number of days and the proportion of each response, the period, applicable rate, between-group difference, its 95% CI-, 95% CI+, and significance probability are shown.
（１）感冒症状の累積日数
　有意差が認められた期間のうち、被験食品群でプラセボ群よりも低値を示した期間は、全期間（プラセボ群：３８．０％、被験食品群：２８．３％、群間差：－９．７％［－１１．４、－８．０］、Ｐ＜０．００１）、前期（プラセボ群：３６．９％、被験食品群：２９．３％、群間差：－７．５％［－９．９、－５．１］、Ｐ＜０．００１）、後期（プラセボ群：３９．２％、被験食品群：２７．３％、群間差：－１１．９％［－１４．３、－９．５］、Ｐ＜０．００１）であった。 (1) Cumulative number of days with cold symptoms Among the periods in which significant differences were observed, the periods in which the test food group showed lower values than the placebo group were the entire period (placebo group: 38.0%, test food group: 28.3%, difference between groups: -9.7% [-11.4, -8.0], P<0.001), the early period (placebo group: 36.9%, test food group: 29.3%, difference between groups: -7.5% [-9.9, -5.1], P<0.001), and the late period (placebo group: 39.2%, test food group: 27.3%, difference between groups: -11.9% [-14.3, -9.5], P<0.001).
（２）全身倦怠感の累積日数
　有意差が認められた期間のうち、被験食品群でプラセボ群よりも低値を示した期間は、後期（プラセボ群：１１．３％、被験食品群：８．５％、群間差：－２．８％［－４．３、－１．３］、Ｐ＜０．００１）であった。 (2) Cumulative number of days with general fatigue Among the periods in which a significant difference was observed, the period in which the test food group showed lower values than the placebo group was the later period (placebo group: 11.3%, test food group: 8.5%, difference between groups: -2.8% [-4.3, -1.3], P<0.001).
（３）寒気の累積日数
　有意差が認められた期間のうち、被験食品群でプラセボ群よりも低値を示した期間は、後期（プラセボ群：１．７％、被験食品群：０．９％、群間差：－０．８％［－１．４、－０．２］、Ｐ＝０．００６）であった。 (3) Cumulative number of days with chills Among the periods in which a significant difference was observed, the period in which the test food group showed lower values than the placebo group was the later period (placebo group: 1.7%, test food group: 0.9%, difference between groups: -0.8% [-1.4, -0.2], P = 0.006).
（４）疲労の累積日数
　有意差が認められた期間のうち、被験食品群でプラセボ群よりも低値を示した期間は、全期間（プラセボ群：２２．８％、被験食品群：１７．５％、群間差：－５．４％［－６．８、－３．９］、Ｐ＜０．００１）、前期（プラセボ群：２１．５％、被験食品群：１８．９％、群間差：－２．６％［－４．６、－０．６］、Ｐ＝０．０１３）、後期（プラセボ群：２４．１％、被験食品群：１６．０％、群間差：－８．２％［－１０．２、－６．１］、Ｐ＜０．００１）であった。 (4) Cumulative number of days of fatigue Among the periods in which significant differences were observed, the periods in which the test food group showed lower values than the placebo group were the entire period (placebo group: 22.8%, test food group: 17.5%, difference between groups: -5.4% [-6.8, -3.9], P<0.001), the early period (placebo group: 21.5%, test food group: 18.9%, difference between groups: -2.6% [-4.6, -0.6], P=0.013), and the late period (placebo group: 24.1%, test food group: 16.0%, difference between groups: -8.2% [-10.2, -6.1], P<0.001).
（５）くしゃみの累積日数
　有意差が認められた期間のうち、被験食品群でプラセボ群よりも低値を示した期間は、全期間（プラセボ群：７．７％、被験食品群：６．２％、群間差：－１．５％［－２．４、－０．６］、Ｐ＝０．００１）、前期（プラセボ群：６．８％、被験食品群：５．２％、群間差：－１．６％［－２．８、－０．４］、Ｐ＝０．００９）であった。 (5) Cumulative number of days with sneezing Among the periods in which significant differences were observed, the periods in which the test food group showed lower values than the placebo group were the entire period (placebo group: 7.7%, test food group: 6.2%, difference between groups: -1.5% [-2.4, -0.6], P = 0.001) and the previous period (placebo group: 6.8%, test food group: 5.2%, difference between groups: -1.6% [-2.8, -0.4], P = 0.009).
（６）鼻汁の累積日数
　有意差が認められた期間のうち、被験食品群でプラセボ群よりも低値を示した期間は、全期間（プラセボ群：１１．７％、被験食品群：９．０％、群間差：－２．７％［－３．７、－１．６］、Ｐ＜０．００１）、前期（プラセボ群：１０．３％、被験食品群：８．６％、群間差：－１．８％［－３．２、－０．３］、Ｐ＝０．０２１）、後期（プラセボ群：１３．０％、被験食品群：９．５％、群間差：－３．５％［－５．２、－１．９］、Ｐ＜０．００１）であった。 (6) Cumulative number of days with nasal runnyness Among the periods in which significant differences were observed, the periods in which the test food group showed lower values than the placebo group were the entire period (placebo group: 11.7%, test food group: 9.0%, difference between groups: -2.7% [-3.7, -1.6], P<0.001), the early period (placebo group: 10.3%, test food group: 8.6%, difference between groups: -1.8% [-3.2, -0.3], P=0.021), and the late period (placebo group: 13.0%, test food group: 9.5%, difference between groups: -3.5% [-5.2, -1.9], P<0.001).
（７）鼻閉の累積日数
　有意差が認められた期間のうち、被験食品群でプラセボ群よりも低値を示した期間は、全期間（プラセボ群：５．３％、被験食品群：３．３％、群間差：－２．０％［－２．７、－１．３］、Ｐ＜０．００１）、後期（プラセボ群：６．４％、被験食品群：３．２％、群間差：－３．２％［－４．３、－２．２］、Ｐ＜０．００１）であった。 (7) Cumulative number of days with nasal congestion Among the periods in which significant differences were observed, the periods in which the test food group showed lower values than the placebo group were the entire period (placebo group: 5.3%, test food group: 3.3%, difference between groups: -2.0% [-2.7, -1.3], P<0.001) and the late period (placebo group: 6.4%, test food group: 3.2%, difference between groups: -3.2% [-4.3, -2.2], P<0.001).
（８）のどの痛みの累積日数
　有意差が認められた期間のうち、被験食品群でプラセボ群よりも低値を示した期間は、全期間（プラセボ群：４．２％、被験食品群：３．３％、群間差：－０．９％［－１．５、－０．２］、Ｐ＝０．０１６）、後期（プラセボ群：４．０％、被験食品群：２．２％、群間差：－１．８％［－２．７、－０．９］、Ｐ＜０．００１）であった。 (8) Cumulative number of days with sore throat Among the periods in which significant differences were observed, the periods in which the test food group showed lower values than the placebo group were the entire period (placebo group: 4.2%, test food group: 3.3%, difference between groups: -0.9% [-1.5, -0.2], P = 0.016) and the late period (placebo group: 4.0%, test food group: 2.2%, difference between groups: -1.8% [-2.7, -0.9], P < 0.001).
（９）せきの累積日数
　有意差が認められた期間のうち、被験食品群でプラセボ群よりも低値を示した期間は、全期間（プラセボ群：４．５％、被験食品群：２．５％、群間差：－２．０％［－２．７、－１．３］、Ｐ＜０．００１）、前期（プラセボ群：４．４％、被験食品群：２．６％、群間差：－１．８％［－２．７、－０．８］、Ｐ＜０．００１）、後期（プラセボ群：４．６％、被験食品群：２．４％、群間差：－２．２％［－３．１、－１．３］、Ｐ＜０．００１）であった。 (9) Cumulative number of days with cough Among the periods in which significant differences were observed, the periods in which the test food group showed lower values than the placebo group were the entire period (placebo group: 4.5%, test food group: 2.5%, difference between groups: -2.0% [-2.7, -1.3], P<0.001), the early period (placebo group: 4.4%, test food group: 2.6%, difference between groups: -1.8% [-2.7, -0.8], P<0.001), and the late period (placebo group: 4.6%, test food group: 2.4%, difference between groups: -2.2% [-3.1, -1.3], P<0.001).
（１０）筋肉痛の累積日数
　有意差が認められた期間のうち、被験食品群でプラセボ群よりも低値を示した期間は、全期間（プラセボ群：５．２％、被験食品群：３．３％、群間差：－２．０％［－２．７、－１．２］、Ｐ＜０．００１）、後期（プラセボ群：５．７％、被験食品群：２．７％、群間差：－３．１％［－４．１、－２．１］、Ｐ＜０．００１）であった。 (10) Cumulative number of days with muscle pain Among the periods in which significant differences were observed, the periods in which the test food group showed lower values than the placebo group were the entire period (placebo group: 5.2%, test food group: 3.3%, difference between groups: -2.0% [-2.7, -1.2], P<0.001) and the late period (placebo group: 5.7%, test food group: 2.7%, difference between groups: -3.1% [-4.1, -2.1], P<0.001).
（１１）全身倦怠感の重症度１の割合
　有意差が認められた期間のうち、被験食品群でプラセボ群よりも高値を示した期間は、後期（プラセボ群：６６．４％、被験食品群：６９．０％、群間差：２．６％［０．２、５．０］、Ｐ＝０．０３３）であった。 (11) Proportion of people with general fatigue severity level 1 Among the periods in which a significant difference was observed, the period in which the test food group showed higher values than the placebo group was the later period (placebo group: 66.4%, test food group: 69.0%, difference between groups: 2.6% [0.2, 5.0], P = 0.033).
（１２）全身倦怠感の重症度４の割合
　有意差が認められた期間のうち、被験食品群でプラセボ群よりも低値を示した期間は、後期（プラセボ群：２．２％、被験食品群：１．２％、群間差：－１．０％［－１．７、－０．３］、Ｐ＝０．００４）であり、高値を示した期間は、前期（プラセボ群：２．１％、被験食品群：２．９％、群間差：０．８％［０．０、１．６］、Ｐ＝０．０４５）であった。 (12) Proportion of people with general fatigue severity level 4 Among the periods in which significant differences were observed, the period in which the test food group showed lower values than the placebo group was the later period (placebo group: 2.2%, test food group: 1.2%, difference between groups: -1.0% [-1.7, -0.3], P = 0.004), and the period in which the test food group showed higher values was the early period (placebo group: 2.1%, test food group: 2.9%, difference between groups: 0.8% [0.0, 1.6], P = 0.045).
（１３）全身倦怠感の重症度５の割合
　有意差が認められた期間のうち、被験食品群でプラセボ群よりも低値を示した期間は、全期間（プラセボ群：０．７％、被験食品群：０．３％、群間差：－０．４％［－０．７、－０．２］、Ｐ＝０．００２）、後期（プラセボ群：１．１％、被験食品群：０．４％、群間差：－０．７％［－１．２、－０．３］、Ｐ＝０．００１）であった。 (13) Proportion of people with general fatigue severity level 5 Among the periods in which significant differences were observed, the periods in which the test food group showed lower values than the placebo group were the entire period (placebo group: 0.7%, test food group: 0.3%, difference between groups: -0.4% [-0.7, -0.2], P = 0.002) and the late period (placebo group: 1.1%, test food group: 0.4%, difference between groups: -0.7% [-1.2, -0.3], P = 0.001).
（１４）寒気の重症度１の割合
　有意差が認められた期間のうち、被験食品群でプラセボ群よりも高値を示した期間は、全期間（プラセボ群：８５．４％、被験食品群：８９．２％、群間差：３．７％［２．５、４．９］、Ｐ＜０．００１）、前期（プラセボ群：８４．２％、被験食品群：８６．７％、群間差：２．５％［０．７、４．３］、Ｐ＝０．００７）、後期（プラセボ群：８６．７％、被験食品群：９１．６％、群間差：４．９％［３．３、６．５］、Ｐ＜０．００１）であった。 (14) Proportion of chills with severity level 1 Among the periods in which significant differences were observed, the periods in which the test food group showed higher values than the placebo group were the entire period (placebo group: 85.4%, test food group: 89.2%, difference between groups: 3.7% [2.5, 4.9], P<0.001), the early period (placebo group: 84.2%, test food group: 86.7%, difference between groups: 2.5% [0.7, 4.3], P=0.007), and the late period (placebo group: 86.7%, test food group: 91.6%, difference between groups: 4.9% [3.3, 6.5], P<0.001).
（１５）寒気の重症度２の割合
　有意差が認められた期間のうち、被験食品群でプラセボ群よりも低値を示した期間は、全期間（プラセボ群：１２．５％、被験食品群：９．０％、群間差：－３．５％［－４．６、－２．４］、Ｐ＜０．００１）、前期（プラセボ群：１３．５％、被験食品群：１０．８％、群間差：－２．７％［－４．３、－１．０］、Ｐ＝０．００２）、後期（プラセボ群：１１．６％、被験食品群：７．２％、群間差：－４．３％［－５．８、－２．９］、Ｐ＜０．００１）であった。 (15) Proportion of chills with severity level 2 Among the periods in which significant differences were observed, the periods in which the test food group showed lower values than the placebo group were the entire period (placebo group: 12.5%, test food group: 9.0%, difference between groups: -3.5% [-4.6, -2.4], P<0.001), the early period (placebo group: 13.5%, test food group: 10.8%, difference between groups: -2.7% [-4.3, -1.0], P=0.002), and the late period (placebo group: 11.6%, test food group: 7.2%, difference between groups: -4.3% [-5.8, -2.9], P<0.001).
（１６）寒気の重症度４の割合
　有意差が認められた期間のうち、被験食品群でプラセボ群よりも低値を示した期間は、後期（プラセボ群：０．５％、被験食品群：０．１％、群間差：－０．４％［－０．７、－０．１］、Ｐ＝０．０１９）であった。 (16) Proportion of chills with severity level 4 Among the periods in which significant differences were observed, the period in which the test food group showed lower values than the placebo group was the later period (placebo group: 0.5%, test food group: 0.1%, difference between groups: -0.4% [-0.7, -0.1], P = 0.019).
（１７）熱っぽさの重症度１の割合
　有意差が認められた期間のうち、被験食品群でプラセボ群よりも高値を示した期間は、全期間（プラセボ群：８６．７％、被験食品群：９２．８％、群間差：６．１％［５．０、７．２］、Ｐ＜０．００１）、前期（プラセボ群：８６．３％、被験食品群：９２．１％、群間差：５．８％［４．２、７．３］、Ｐ＜０．００１）、後期（プラセボ群：８７．０％、被験食品群：９３．５％、群間差：６．４％［４．９、８．０］、Ｐ＜０．００１）であった。 (17) Proportion of feverishness severity level 1 Among the periods in which significant differences were observed, the periods in which the test food group showed higher values than the placebo group were the entire period (placebo group: 86.7%, test food group: 92.8%, difference between groups: 6.1% [5.0, 7.2], P<0.001), the early period (placebo group: 86.3%, test food group: 92.1%, difference between groups: 5.8% [4.2, 7.3], P<0.001), and the late period (placebo group: 87.0%, test food group: 93.5%, difference between groups: 6.4% [4.9, 8.0], P<0.001).
（１８）熱っぽさの重症度２の割合
　有意差が認められた期間のうち、被験食品群でプラセボ群よりも低値を示した期間は、全期間（プラセボ群：１１．８％、被験食品群：５．５％、群間差：－６．２％［－７．２、－５．２］、Ｐ＜０．００１）、前期（プラセボ群：１２．４％、被験食品群：６．１％、群間差：－６．４％［－７．８、－４．９］、Ｐ＜０．００１）、後期（プラセボ群：１１．１％、被験食品群：５．０％、群間差：－６．１％［－７．５、－４．７］、Ｐ＜０．００１）であった。 (18) Proportion of fever severity level 2 Among the periods in which significant differences were observed, the periods in which the test food group showed lower values than the placebo group were the entire period (placebo group: 11.8%, test food group: 5.5%, difference between groups: -6.2% [-7.2, -5.2], P<0.001), the early period (placebo group: 12.4%, test food group: 6.1%, difference between groups: -6.4% [-7.8, -4.9], P<0.001), and the late period (placebo group: 11.1%, test food group: 5.0%, difference between groups: -6.1% [-7.5, -4.7], P<0.001).
（１９）熱っぽさの重症度４の割合
　有意差が認められた期間のうち、被験食品群でプラセボ群よりも高値を示した期間は、前期（プラセボ群：０．０％、被験食品群：０．５％、群間差：０．４％［０．２、０．７］、Ｐ＜０．００１）であった。 (19) Proportion of patients with fever severity level 4 Among the periods in which significant differences were observed, the period in which the test food group showed higher values than the placebo group was the early period (placebo group: 0.0%, test food group: 0.5%, difference between groups: 0.4% [0.2, 0.7], P<0.001).
（２０）熱っぽさの重症度５の割合
　有意差が認められた期間のうち、被験食品群でプラセボ群よりも高値を示した期間は、全期間（プラセボ群：０．０％、被験食品群：０．２％、群間差：０．１％［０．０、０．２］、Ｐ＝０．０３８）、前期（プラセボ群：０．０％、被験食品群：０．２％、群間差：０．２％［０．０、０．４］、Ｐ＝０．０１５）であった。 (20) Proportion of patients with fever severity level 5 Among the periods in which significant differences were observed, the periods in which the test food group showed higher values than the placebo group were the entire period (placebo group: 0.0%, test food group: 0.2%, difference between groups: 0.1% [0.0, 0.2], P = 0.038) and the early period (placebo group: 0.0%, test food group: 0.2%, difference between groups: 0.2% [0.0, 0.4], P = 0.015).
（２１）疲労の重症度１の割合
　有意差が認められた期間のうち、被験食品群でプラセボ群よりも高値を示した期間は、全期間（プラセボ群：４６．３％、被験食品群：５７．３％、群間差：１１．０％［９．２、１２．８］、Ｐ＜０．００１）、前期（プラセボ群：４７．０％、被験食品群：５４．６％、群間差：７．６％［５．１、１０．２］、Ｐ＜０．００１）、後期（プラセボ群：４５．６％、被験食品群：６０．０％、群間差：１４．３％［１１．８、１６．９］、Ｐ＜０．００１）であった。 (21) Proportion of fatigue severity level 1 Among the periods in which significant differences were observed, the periods in which the test food group showed higher values than the placebo group were the entire period (placebo group: 46.3%, test food group: 57.3%, difference between groups: 11.0% [9.2, 12.8], P<0.001), the early period (placebo group: 47.0%, test food group: 54.6%, difference between groups: 7.6% [5.1, 10.2], P<0.001), and the late period (placebo group: 45.6%, test food group: 60.0%, difference between groups: 14.3% [11.8, 16.9], P<0.001).
（２２）疲労の重症度２の割合
　有意差が認められた期間のうち、被験食品群でプラセボ群よりも低値を示した期間は、全期間（プラセボ群：３０．９％、被験食品群：２５．１％、群間差：－５．７％［－７．３、－４．１］、Ｐ＜０．００１）、前期（プラセボ群：３１．５％、被験食品群：２６．４％、群間差：－５．０％［－７．３、－２．７］、Ｐ＜０．００１）、後期（プラセボ群：３０．２％、被験食品群：２３．８％、群間差：－６．４％［－８．７、－４．２］、Ｐ＜０．００１）であった。 (22) Proportion of fatigue severity level 2 Among the periods in which significant differences were observed, the periods in which the test food group showed lower values than the placebo group were the entire period (placebo group: 30.9%, test food group: 25.1%, difference between groups: -5.7% [-7.3, -4.1], P<0.001), the early period (placebo group: 31.5%, test food group: 26.4%, difference between groups: -5.0% [-7.3, -2.7], P<0.001), and the late period (placebo group: 30.2%, test food group: 23.8%, difference between groups: -6.4% [-8.7, -4.2], P<0.001).
（２３）疲労の重症度３の割合
　有意差が認められた期間のうち、被験食品群でプラセボ群よりも低値を示した期間は、全期間（プラセボ群：１６．４％、被験食品群：１２．９％、群間差：－３．５％［－４．８、－２．２］、Ｐ＜０．００１）、前期（プラセボ群：１６．２％、被験食品群：１３．３％、群間差：－２．８％［－４．６、－１．０］、Ｐ＝０．００２）、後期（プラセボ群：１６．７％、被験食品群：１２．４％、群間差：－４．２％［－６．０、－２．４］、Ｐ＜０．００１）であった。 (23) Proportion of fatigue severity level 3 Among the periods in which significant differences were observed, the periods in which the test food group showed lower values than the placebo group were the entire period (placebo group: 16.4%, test food group: 12.9%, difference between groups: -3.5% [-4.8, -2.2], P<0.001), the early period (placebo group: 16.2%, test food group: 13.3%, difference between groups: -2.8% [-4.6, -1.0], P=0.002), and the late period (placebo group: 16.7%, test food group: 12.4%, difference between groups: -4.2% [-6.0, -2.4], P<0.001).
（２４）疲労の重症度４の割合
　有意差が認められた期間のうち、被験食品群でプラセボ群よりも低値を示した期間は、全期間（プラセボ群：５．１％、被験食品群：３．９％、群間差：－１．２％［－１．９、－０．５］、Ｐ＝０．００２）、後期（プラセボ群：５．７％、被験食品群：３．１％、群間差：－２．６％［－３．６、－１．５］、Ｐ＜０．００１）であった。 (24) Proportion of people with fatigue severity level 4 Among the periods in which significant differences were observed, the periods in which the test food group showed lower values than the placebo group were the entire period (placebo group: 5.1%, test food group: 3.9%, difference between groups: -1.2% [-1.9, -0.5], P = 0.002) and the late period (placebo group: 5.7%, test food group: 3.1%, difference between groups: -2.6% [-3.6, -1.5], P < 0.001).
（２５）疲労の重症度５の割合
　有意差が認められた期間のうち、被験食品群でプラセボ群よりも低値を示した期間は、全期間（プラセボ群：１．３％、被験食品群：０．７％、群間差：－０．７％［－１．０、－０．３］、Ｐ＜０．００１）、後期（プラセボ群：１．８％、被験食品群：０．４％、群間差：－１．４％［－１．９、－０．８］、Ｐ＜０．００１）であった。 (25) Proportion of people with fatigue severity level 5 Among the periods in which significant differences were observed, the periods in which the test food group showed lower values than the placebo group were the entire period (placebo group: 1.3%, test food group: 0.7%, difference between groups: -0.7% [-1.0, -0.3], P<0.001) and the late period (placebo group: 1.8%, test food group: 0.4%, difference between groups: -1.4% [-1.9, -0.8], P<0.001).
（２６）くしゃみの重症度１の割合
　有意差が認められた期間のうち、被験食品群でプラセボ群よりも高値を示した期間は、全期間（プラセボ群：７４．７％、被験食品群：７９．４％、群間差：４．７％［３．２、６．２］、Ｐ＜０．００１）、前期（プラセボ群：７５．６％、被験食品群：８０．２％、群間差：４．６％［２．５、６．７］、Ｐ＜０．００１）、後期（プラセボ群：７３．８％、被験食品群：７８．６％、群間差：４．８％［２．７、７．０］、Ｐ＜０．００１）であった。 (26) Proportion of sneezing severity level 1 Among the periods in which significant differences were observed, the periods in which the test food group showed higher values than the placebo group were the entire period (placebo group: 74.7%, test food group: 79.4%, difference between groups: 4.7% [3.2, 6.2], P<0.001), the early period (placebo group: 75.6%, test food group: 80.2%, difference between groups: 4.6% [2.5, 6.7], P<0.001), and the late period (placebo group: 73.8%, test food group: 78.6%, difference between groups: 4.8% [2.7, 7.0], P<0.001).
（２７）くしゃみの重症度２の割合
　有意差が認められた期間のうち、被験食品群でプラセボ群よりも低値を示した期間は、全期間（プラセボ群：１７．６％、被験食品群：１４．３％、群間差：－３．３％［－４．７、－２．０］、Ｐ＜０．００１）、前期（プラセボ群：１７．７％、被験食品群：１４．７％、群間差：－３．０％［－４．８、－１．１］、Ｐ＝０．００２）、後期（プラセボ群：１７．６％、被験食品群：１３．９％、群間差：－３．７％［－５．６、－１．９］、Ｐ＜０．００１）であった。 (27) Proportion of sneezing severity level 2 Among the periods in which significant differences were observed, the periods in which the test food group showed lower values than the placebo group were the entire period (placebo group: 17.6%, test food group: 14.3%, difference between groups: -3.3% [-4.7, -2.0], P<0.001), the early period (placebo group: 17.7%, test food group: 14.7%, difference between groups: -3.0% [-4.8, -1.1], P=0.002), and the late period (placebo group: 17.6%, test food group: 13.9%, difference between groups: -3.7% [-5.6, -1.9], P<0.001).
（２８）くしゃみの重症度３の割合
　有意差が認められた期間のうち、被験食品群でプラセボ群よりも低値を示した期間は、全期間（プラセボ群：６．１％、被験食品群：５．２％、群間差：－０．９％［－１．７、－０．１］、Ｐ＝０．０４０）、前期（プラセボ群：５．５％、被験食品群：４．３％、群間差：－１．２％［－２．３、－０．１］、Ｐ＝０．０３５）であった。 (28) Proportion of sneezing severity level 3 Among the periods in which significant differences were observed, the periods in which the test food group showed lower values than the placebo group were the entire period (placebo group: 6.1%, test food group: 5.2%, difference between groups: -0.9% [-1.7, -0.1], P = 0.040) and the previous period (placebo group: 5.5%, test food group: 4.3%, difference between groups: -1.2% [-2.3, -0.1], P = 0.035).
（２９）くしゃみの重症度４の割合
　有意差が認められた期間のうち、被験食品群でプラセボ群よりも低値を示した期間は、全期間（プラセボ群：１．１％、被験食品群：０．７％、群間差：－０．４％［－０．７、－０．１］、Ｐ＝０．０１８）、前期（プラセボ群：１．０％、被験食品群：０．４％、群間差：－０．６％［－１．０、－０．２］、Ｐ＝０．００６）であった。 (29) Proportion of sneezing severity level 4 Among the periods in which significant differences were observed, the periods in which the test food group showed lower values than the placebo group were the entire period (placebo group: 1.1%, test food group: 0.7%, difference between groups: -0.4% [-0.7, -0.1], P = 0.018) and the previous period (placebo group: 1.0%, test food group: 0.4%, difference between groups: -0.6% [-1.0, -0.2], P = 0.006).
（３０）くしゃみの重症度５の割合
　有意差が認められた期間のうち、被験食品群でプラセボ群よりも低値を示した期間は、後期（プラセボ群：０．６％、被験食品群：０．０％、群間差：－０．６％［－０．９、－０．３］、Ｐ＜０．００１）であった。 (30) Proportion of sneezing severity level 5 Among the periods in which significant differences were observed, the period in which the test food group showed lower values than the placebo group was the late period (placebo group: 0.6%, test food group: 0.0%, difference between groups: -0.6% [-0.9, -0.3], P<0.001).
（３１）鼻汁の重症度１の割合
　有意差が認められた期間のうち、被験食品群でプラセボ群よりも高値を示した期間は、全期間（プラセボ群：６９．２％、被験食品群：７５．３％、群間差：６．１％［４．５、７．７］、Ｐ＜０．００１）、前期（プラセボ群：６９．４％、被験食品群：７５．９％、群間差：６．６％［４．３、８．８］、Ｐ＜０．００１）、後期（プラセボ群：６９．１％、被験食品群：７４．７％、群間差：５．６％［３．４、７．９］、Ｐ＜０．００１）であった。 (31) Proportion of patients with nasal discharge severity level 1 Among the periods in which significant differences were observed, the periods in which the test food group showed higher values than the placebo group were the entire period (placebo group: 69.2%, test food group: 75.3%, difference between groups: 6.1% [4.5, 7.7], P<0.001), the early period (placebo group: 69.4%, test food group: 75.9%, difference between groups: 6.6% [4.3, 8.8], P<0.001), and the late period (placebo group: 69.1%, test food group: 74.7%, difference between groups: 5.6% [3.4, 7.9], P<0.001).
（３２）鼻汁の重症度２の割合
　有意差が認められた期間のうち、被験食品群でプラセボ群よりも低値を示した期間は、全期間（プラセボ群：１９．１％、被験食品群：１５．５％、群間差：－３．６％［－４．９、－２．２］、Ｐ＜０．００１）、前期（プラセボ群：２０．３％、被験食品群：１５．５％、群間差：－４．８％［－６．８、－２．９］、Ｐ＜０．００１）、後期（プラセボ群：１７．９％、被験食品群：１５．６％、群間差：－２．３％［－４．２、－０．４］、Ｐ＝０．０１７）であった。 (32) Proportion of nasal discharge severity level 2 Among the periods in which significant differences were observed, the periods in which the test food group showed lower values than the placebo group were the entire period (placebo group: 19.1%, test food group: 15.5%, difference between groups: -3.6% [-4.9, -2.2], P<0.001), the early period (placebo group: 20.3%, test food group: 15.5%, difference between groups: -4.8% [-6.8, -2.9], P<0.001), and the late period (placebo group: 17.9%, test food group: 15.6%, difference between groups: -2.3% [-4.2, -0.4], P=0.017).
（３３）鼻汁の重症度３の割合
　有意差が認められた期間のうち、被験食品群でプラセボ群よりも低値を示した期間は、全期間（プラセボ群：８．７％、被験食品群：７．０％、群間差：－１．７％［－２．７、－０．７］、Ｐ＜０．００１）、前期（プラセボ群：７．８％、被験食品群：６．２％、群間差：－１．６％［－２．９、－０．４］、Ｐ＝０．０１３）、後期（プラセボ群：９．６％、被験食品群：７．９％、群間差：－１．８％［－３．２、－０．３］、Ｐ＝０．０１７）であった。 (33) Proportion of nasal discharge severity level 3 Among the periods in which significant differences were observed, the periods in which the test food group showed lower values than the placebo group were the entire period (placebo group: 8.7%, test food group: 7.0%, difference between groups: -1.7% [-2.7, -0.7], P < 0.001), the early period (placebo group: 7.8%, test food group: 6.2%, difference between groups: -1.6% [-2.9, -0.4], P = 0.013), and the late period (placebo group: 9.6%, test food group: 7.9%, difference between groups: -1.8% [-3.2, -0.3], P = 0.017).
（３４）鼻汁の重症度４の割合
　有意差が認められた期間のうち、被験食品群でプラセボ群よりも低値を示した期間は、全期間（プラセボ群：２．５％、被験食品群：１．１％、群間差：－１．４％［－１．８、－０．９］、Ｐ＜０．００１）、後期（プラセボ群：２．８％、被験食品群：０．７％、群間差：－２．１％［－２．７、－１．４］、Ｐ＜０．００１）であった。 (34) Proportion of patients with nasal discharge severity level 4 Among the periods in which significant differences were observed, the periods in which the test food group showed lower values than the placebo group were the entire period (placebo group: 2.5%, test food group: 1.1%, difference between groups: -1.4% [-1.8, -0.9], P<0.001) and the late period (placebo group: 2.8%, test food group: 0.7%, difference between groups: -2.1% [-2.7, -1.4], P<0.001).
（３５）鼻汁の重症度５の割合
　有意差が認められた期間のうち、被験食品群でプラセボ群よりも高値を示した期間は、全期間（プラセボ群：０．５％、被験食品群：０．９％、群間差：０．４％［０．１、０．７］、Ｐ＝０．００７）、前期（プラセボ群：０．３％、被験食品群：０．９％、群間差：０．５％［０．１、０．９］、Ｐ＝０．００７）であった。 (35) Proportion of nasal discharge severity level 5 Among the periods in which significant differences were observed, the periods in which the test food group showed higher values than the placebo group were the entire period (placebo group: 0.5%, test food group: 0.9%, difference between groups: 0.4% [0.1, 0.7], P = 0.007) and the early period (placebo group: 0.3%, test food group: 0.9%, difference between groups: 0.5% [0.1, 0.9], P = 0.007).
（３６）鼻閉の重症度１の割合
　有意差が認められた期間のうち、被験食品群でプラセボ群よりも低値を示した期間は、全期間（プラセボ群：８０．３％、被験食品群：８６．９％、群間差：６．６％［５．３、７．９］、Ｐ＜０．００１）、前期（プラセボ群：８１．６％、被験食品群：８６．０％、群間差：４．４％［２．５、６．３］、Ｐ＜０．００１）、後期（プラセボ群：７９．１％、被験食品群：８７．８％、群間差：８．８％［６．９、１０．７］、Ｐ＜０．００１）であった。 (36) Proportion of patients with nasal congestion severity level 1 Among the periods in which significant differences were observed, the periods in which the test food group showed lower values than the placebo group were the entire period (placebo group: 80.3%, test food group: 86.9%, difference between groups: 6.6% [5.3, 7.9], P<0.001), the early period (placebo group: 81.6%, test food group: 86.0%, difference between groups: 4.4% [2.5, 6.3], P<0.001), and the late period (placebo group: 79.1%, test food group: 87.8%, difference between groups: 8.8% [6.9, 10.7], P<0.001).
（３７）鼻閉の重症度２の割合
　有意差が認められた期間のうち、被験食品群でプラセボ群よりも低値を示した期間は、全期間（プラセボ群：１４．４％、被験食品群：９．７％、群間差：－４．７％［－５．９、－３．５］、Ｐ＜０．００１）、前期（プラセボ群：１４．３％、被験食品群：１０．６％、群間差：－３．７％［－５．３、－２．０］、Ｐ＜０．００１）、後期（プラセボ群：１４．５％、被験食品群：８．８％、群間差：－５．８％［－７．４、－４．１］、Ｐ＜０．００１）であった。 (37) Proportion of nasal congestion severity level 2 Among the periods in which significant differences were observed, the periods in which the test food group showed lower values than the placebo group were the entire period (placebo group: 14.4%, test food group: 9.7%, difference between groups: -4.7% [-5.9, -3.5], P<0.001), the early period (placebo group: 14.3%, test food group: 10.6%, difference between groups: -3.7% [-5.3, -2.0], P<0.001), and the late period (placebo group: 14.5%, test food group: 8.8%, difference between groups: -5.8% [-7.4, -4.1], P<0.001).
（３８）鼻閉の重症度３の割合
　有意差が認められた期間のうち、被験食品群でプラセボ群よりも低値を示した期間は、全期間（プラセボ群：３．９％、被験食品群：２．５％、群間差：－１．４％［－２．０、－０．８］、Ｐ＜０．００１）、後期（プラセボ群：４．７％、被験食品群：２．３％、群間差：－２．４％［－３．３、－１．４］、Ｐ＜０．００１）であった。 (38) Proportion of nasal congestion severity level 3 Among the periods in which significant differences were observed, the periods in which the test food group showed lower values than the placebo group were the entire period (placebo group: 3.9%, test food group: 2.5%, difference between groups: -1.4% [-2.0, -0.8], P<0.001) and the late period (placebo group: 4.7%, test food group: 2.3%, difference between groups: -2.4% [-3.3, -1.4], P<0.001).
（３９）鼻閉の重症度４の割合
　有意差が認められた期間のうち、被験食品群でプラセボ群よりも低値を示した期間は、後期（プラセボ群：１．５％、被験食品群：０．８％、群間差：－０．７％［－１．２、－０．１］、Ｐ＝０．０２２）であった。 (39) Proportion of patients with nasal congestion severity level 4 Among the periods in which a significant difference was observed, the period in which the test food group showed lower values than the placebo group was the late period (placebo group: 1.5%, test food group: 0.8%, difference between groups: -0.7% [-1.2, -0.1], P = 0.022).
（４０）鼻閉の重症度５の割合
　有意差が認められた期間のうち、被験食品群でプラセボ群よりも低値を示した期間は、全期間（プラセボ群：０．３％、被験食品群：０．０％、群間差：－０．３％［－０．４、－０．１］、Ｐ＜０．００１）、前期（プラセボ群：０．３％、被験食品群：０．０％、群間差：－０．３％［－０．５、－０．１］、Ｐ＝０．００４）、後期（プラセボ群：０．２％、被験食品群：０．０％、群間差：－０．２％［－０．４、０．０］、Ｐ＝０．０３１）であった。 (40) Proportion of nasal congestion severity level 5 Among the periods in which significant differences were observed, the periods in which the test food group showed lower values than the placebo group were the entire period (placebo group: 0.3%, test food group: 0.0%, difference between groups: -0.3% [-0.4, -0.1], P < 0.001), the early period (placebo group: 0.3%, test food group: 0.0%, difference between groups: -0.3% [-0.5, -0.1], P = 0.004), and the late period (placebo group: 0.2%, test food group: 0.0%, difference between groups: -0.2% [-0.4, 0.0], P = 0.031).
（４１）のどの痛みの重症度１の割合
　有意差が認められた期間のうち、被験食品群でプラセボ群よりも高値を示した期間は、全期間（プラセボ群：８１．６％、被験食品群：９０．３％、群間差：８．７％［７．４、９．９］、Ｐ＜０．００１）、前期（プラセボ群：８１．４％、被験食品群：８８．４％、群間差：７．０％［５．１、８．８］、Ｐ＜０．００１）、後期（プラセボ群：８１．９％、被験食品群：９２．２％、群間差：１０．３％［８．６、１２．０］、Ｐ＜０．００１）であった。 (41) Proportion of sore throat severity level 1 Among the periods in which significant differences were observed, the periods in which the test food group showed higher values than the placebo group were the entire period (placebo group: 81.6%, test food group: 90.3%, difference between groups: 8.7% [7.4, 9.9], P<0.001), the early period (placebo group: 81.4%, test food group: 88.4%, difference between groups: 7.0% [5.1, 8.8], P<0.001), and the late period (placebo group: 81.9%, test food group: 92.2%, difference between groups: 10.3% [8.6, 12.0], P<0.001).
（４２）のどの痛みの重症度２の割合
　有意差が認められた期間のうち、被験食品群でプラセボ群よりも低値を示した期間は、全期間（プラセボ群：１４．２％、被験食品群：６．３％、群間差：－７．９％［－９．０、－６．８］、Ｐ＜０．００１）、前期（プラセボ群：１４．３％、被験食品群：７．２％、群間差：－７．１％［－８．６、－５．５］、Ｐ＜０．００１）、後期（プラセボ群：１４．１％、被験食品群：５．４％、群間差：－８．８％［－１０．３、－７．３］、Ｐ＜０．００１）であった。 (42) Proportion of sore throat severity level 2 Among the periods in which significant differences were observed, the periods in which the test food group showed lower values than the placebo group were the entire period (placebo group: 14.2%, test food group: 6.3%, difference between groups: -7.9% [-9.0, -6.8], P<0.001), the early period (placebo group: 14.3%, test food group: 7.2%, difference between groups: -7.1% [-8.6, -5.5], P<0.001), and the late period (placebo group: 14.1%, test food group: 5.4%, difference between groups: -8.8% [-10.3, -7.3], P<0.001).
（４３）のどの痛みの重症度３の割合
　有意差が認められた期間のうち、被験食品群でプラセボ群よりも低値を示した期間は、後期（プラセボ群：２．８％、被験食品群：１．９％、群間差：－０．９％［－１．７、－０．１］、Ｐ＝０．０２７）であった。 (43) Proportion of sore throat severity level 3 Among the periods in which a significant difference was observed, the period in which the test food group showed lower values than the placebo group was the late period (placebo group: 2.8%, test food group: 1.9%, difference between groups: -0.9% [-1.7, -0.1], P = 0.027).
（４４）のどの痛みの重症度４の割合
　有意差が認められた期間のうち、被験食品群でプラセボ群よりも低値を示した期間は、全期間（プラセボ群：１．０％、被験食品群：０．５％、群間差：－０．４％［－０．７、－０．１］、Ｐ＝０．００８）、後期（プラセボ群：１．０％、被験食品群：０．３％、群間差：－０．７％［－１．１、－０．３］、Ｐ＜０．００１）であった。 (44) Proportion of sore throat severity level 4 Among the periods in which significant differences were observed, the periods in which the test food group showed lower values than the placebo group were the entire period (placebo group: 1.0%, test food group: 0.5%, difference between groups: -0.4% [-0.7, -0.1], P = 0.008) and the late period (placebo group: 1.0%, test food group: 0.3%, difference between groups: -0.7% [-1.1, -0.3], P < 0.001).
（４５）のどの痛みの重症度５の割合
　有意差が認められた期間のうち、被験食品群でプラセボ群よりも低値を示した期間は、後期（プラセボ群：０．２％、被験食品群：０．０％、群間差：－０．２％［－０．４、０．０］、Ｐ＝０．０３１）であった。 (45) Proportion of patients with sore throat severity level 5 Among the periods in which a significant difference was observed, the period in which the test food group showed lower values than the placebo group was the later period (placebo group: 0.2%, test food group: 0.0%, difference between groups: -0.2% [-0.4, 0.0], P = 0.031).
（４６）せきの重症度１の割合
　有意差が認められた期間のうち、被験食品群でプラセボ群よりも高値を示した期間は、全期間（プラセボ群：８２．７％、被験食品群：８８．８％、群間差：６．１％［４．８、７．３］、Ｐ＜０．００１）、前期（プラセボ群：８２．６％、被験食品群：８８．２％、群間差：５．６％［３．８、７．４］、Ｐ＜０．００１）、後期（プラセボ群：８２．８％、被験食品群：８９．４％、群間差：６．６％［４．９、８．４］、Ｐ＜０．００１）であった。 (46) Proportion of cough severity level 1 Among the periods in which significant differences were observed, the periods in which the test food group showed higher values than the placebo group were the entire period (placebo group: 82.7%, test food group: 88.8%, difference between groups: 6.1% [4.8, 7.3], P<0.001), the early period (placebo group: 82.6%, test food group: 88.2%, difference between groups: 5.6% [3.8, 7.4], P<0.001), and the late period (placebo group: 82.8%, test food group: 89.4%, difference between groups: 6.6% [4.9, 8.4], P<0.001).
（４７）せきの重症度２の割合
　有意差が認められた期間のうち、被験食品群でプラセボ群よりも低値を示した期間は、全期間（プラセボ群：１２．８％、被験食品群：８．６％、群間差：－４．２％［－５．３、－３．１］、Ｐ＜０．００１）、前期（プラセボ群：１３．０％、被験食品群：９．２％、群間差：－３．８％［－５．４、－２．２］、Ｐ＜０．００１）、後期（プラセボ群：１２．６％、被験食品群：８．０％、群間差：－４．６％［－６．２、－３．１］、Ｐ＜０．００１）であった。 (47) Proportion of cough severity level 2 Among the periods in which significant differences were observed, the periods in which the test food group showed lower values than the placebo group were the entire period (placebo group: 12.8%, test food group: 8.6%, difference between groups: -4.2% [-5.3, -3.1], P < 0.001), the early period (placebo group: 13.0%, test food group: 9.2%, difference between groups: -3.8% [-5.4, -2.2], P < 0.001), and the late period (placebo group: 12.6%, test food group: 8.0%, difference between groups: -4.6% [-6.2, -3.1], P < 0.001).
（４８）せきの重症度３の割合
　有意差が認められた期間のうち、被験食品群でプラセボ群よりも低値を示した期間は、全期間（プラセボ群：３．１％、被験食品群：２．０％、群間差：－１．１％［－１．７、－０．５］、Ｐ＜０．００１）、前期（プラセボ群：３．２％、被験食品群：１．８％、群間差：－１．４％［－２．２、－０．６］、Ｐ＜０．００１）、後期（プラセボ群：３．０％、被験食品群：２．２％、群間差：－０．８％［－１．７、０．０］、Ｐ＝０．０４３）であった。 (48) Proportion of cough severity level 3 Among the periods in which significant differences were observed, the periods in which the test food group showed lower values than the placebo group were the entire period (placebo group: 3.1%, test food group: 2.0%, difference between groups: -1.1% [-1.7, -0.5], P < 0.001), the early period (placebo group: 3.2%, test food group: 1.8%, difference between groups: -1.4% [-2.2, -0.6], P < 0.001), and the late period (placebo group: 3.0%, test food group: 2.2%, difference between groups: -0.8% [-1.7, 0.0], P = 0.043).
（４９）せきの重症度４の割合
　有意差が認められた期間のうち、被験食品群でプラセボ群よりも低値を示した期間は、全期間（プラセボ群：１．３％、被験食品群：０．４％、群間差：－０．９％［－１．２、－０．６］、Ｐ＜０．００１）、前期（プラセボ群：１．１％、被験食品群：０．６％、群間差：－０．５％［－１．０、－０．１］、Ｐ＝０．０３２）、後期（プラセボ群：１．５％、被験食品群：０．２％、群間差：－１．３％［－１．８、－０．８］、Ｐ＜０．００１）であった。 (49) Proportion of cough severity level 4 Among the periods in which significant differences were observed, the periods in which the test food group showed lower values than the placebo group were the entire period (placebo group: 1.3%, test food group: 0.4%, difference between groups: -0.9% [-1.2, -0.6], P < 0.001), the early period (placebo group: 1.1%, test food group: 0.6%, difference between groups: -0.5% [-1.0, -0.1], P = 0.032), and the late period (placebo group: 1.5%, test food group: 0.2%, difference between groups: -1.3% [-1.8, -0.8], P < 0.001).
（５０）関節痛の重症度１の割合
　有意差が認められた期間のうち、被験食品群でプラセボ群よりも高値を示した期間は、全期間（プラセボ群：８０．３％、被験食品群：８７．７％、群間差：７．４％［６．０、８．７］、Ｐ＜０．００１）、前期（プラセボ群：８１．７％、被験食品群：８６．７％、群間差：５．０％［３．２、６．９］、Ｐ＜０．００１）、後期（プラセボ群：７９．０％、被験食品群：８８．７％、群間差：９．７％［７．８、１１．６］、Ｐ＜０．００１）であった。 (50) Proportion of joint pain severity level 1 Among the periods in which significant differences were observed, the periods in which the test food group showed higher values than the placebo group were the entire period (placebo group: 80.3%, test food group: 87.7%, difference between groups: 7.4% [6.0, 8.7], P<0.001), the early period (placebo group: 81.7%, test food group: 86.7%, difference between groups: 5.0% [3.2, 6.9], P<0.001), and the late period (placebo group: 79.0%, test food group: 88.7%, difference between groups: 9.7% [7.8, 11.6], P<0.001).
（５１）関節痛の重症度２の割合
　有意差が認められた期間のうち、被験食品群でプラセボ群より低値を示した期間は、全期間（プラセボ群：１６．２％、被験食品群：８．７％、群間差：－７．５％［－８．７、－６．３］、Ｐ＜０．００１）、前期（プラセボ群：１４．８％、被験食品群：９．６％、群間差：－５．２％［－６．８、－３．５］、Ｐ＜０．００１）、後期（プラセボ群：１７．７％、被験食品群：７．８％、群間差：－９．８％［－１１．５、－８．１］、Ｐ＜０．００１）であった。 (51) Proportion of joint pain severity level 2 Among the periods in which significant differences were observed, the periods in which the test food group showed lower values than the placebo group were the entire period (placebo group: 16.2%, test food group: 8.7%, difference between groups: -7.5% [-8.7, -6.3], P<0.001), the early period (placebo group: 14.8%, test food group: 9.6%, difference between groups: -5.2% [-6.8, -3.5], P<0.001), and the late period (placebo group: 17.7%, test food group: 7.8%, difference between groups: -9.8% [-11.5, -8.1], P<0.001).
（５２）関節痛の重症度３の割合
　有意差が認められた期間のうち、被験食品群でプラセボ群より低値を示した期間は、全期間（プラセボ群：３．０％、被験食品群：２．１％、群間差：－０．９％［－１．５、－０．４］、Ｐ＝０．００２）、前期（プラセボ群：３．２％、被験食品群：２．１％、群間差：－１．１％［－１．９、－０．３］、Ｐ＝０．００８）であった。 (52) Proportion of joint pain severity level 3 Among the periods in which significant differences were observed, the periods in which the test food group showed lower values than the placebo group were the entire period (placebo group: 3.0%, test food group: 2.1%, difference between groups: -0.9% [-1.5, -0.4], P = 0.002) and the previous period (placebo group: 3.2%, test food group: 2.1%, difference between groups: -1.1% [-1.9, -0.3], P = 0.008).
（５３）関節痛の重症度４の割合
　有意差が認められた期間のうち、被験食品群でプラセボ群より高値を示した期間は、全期間（プラセボ群：０．４％、被験食品群：１．４％、群間差：１．０％［０．７、１．３］、Ｐ＜０．００１）、前期（プラセボ群：０．３％、被験食品群：１．６％、群間差：１．３％［０．８、１．８］、Ｐ＜０．００１）、後期（プラセボ群：０．５％、被験食品群：１．２％、群間差：０．７％［０．３、１．２］、Ｐ＝０．００２）であった。 (53) Proportion of joint pain severity level 4 Among the periods in which significant differences were observed, the periods in which the test food group showed higher values than the placebo group were the entire period (placebo group: 0.4%, test food group: 1.4%, difference between groups: 1.0% [0.7, 1.3], P<0.001), the early period (placebo group: 0.3%, test food group: 1.6%, difference between groups: 1.3% [0.8, 1.8], P<0.001), and the late period (placebo group: 0.5%, test food group: 1.2%, difference between groups: 0.7% [0.3, 1.2], P=0.002).
（５４）筋肉痛の重症度１の割合
　有意差が認められた期間のうち、被験食品群でプラセボ群より高値を示した期間は、全期間（プラセボ群：７９．０％、被験食品群：８７．０％、群間差：８．１％［６．７、９．４］、Ｐ＜０．００１）、前期（プラセボ群：７９．３％、被験食品群：８５．６％、群間差：６．３％［４．４、８．３］、Ｐ＜０．００１）、後期（プラセボ群：７８．６％、被験食品群：８８．４％、群間差：９．８％［７．９、１１．７］、Ｐ＜０．００１）であった。 (54) Proportion of muscle pain with severity level 1 Among the periods in which significant differences were observed, the periods in which the test food group showed higher values than the placebo group were the entire period (placebo group: 79.0%, test food group: 87.0%, difference between groups: 8.1% [6.7, 9.4], P<0.001), the early period (placebo group: 79.3%, test food group: 85.6%, difference between groups: 6.3% [4.4, 8.3], P<0.001), and the late period (placebo group: 78.6%, test food group: 88.4%, difference between groups: 9.8% [7.9, 11.7], P<0.001).
（５５）筋肉痛の重症度２の割合
　有意差が認められた期間のうち、被験食品群でプラセボ群より低値を示した期間は、全期間（プラセボ群：１５．８％、被験食品群：９．６％、群間差：－６．２％［－７．４、－５．０］、Ｐ＜０．００１）、前期（プラセボ群：１６．０％、被験食品群：１０．５％、群間差：－５．５％［－７．２、－３．８］、Ｐ＜０．００１）、後期（プラセボ群：１５．７％、被験食品群：８．７％、群間差：－７．０％［－８．６、－５．３］、Ｐ＜０．００１）であった。 (55) Proportion of muscle pain severity level 2 Among the periods in which significant differences were observed, the periods in which the test food group showed lower values than the placebo group were the entire period (placebo group: 15.8%, test food group: 9.6%, difference between groups: -6.2% [-7.4, -5.0], P<0.001), the early period (placebo group: 16.0%, test food group: 10.5%, difference between groups: -5.5% [-7.2, -3.8], P<0.001), and the late period (placebo group: 15.7%, test food group: 8.7%, difference between groups: -7.0% [-8.6, -5.3], P<0.001).
（５６）筋肉痛の重症度３の割合
　有意差が認められた期間のうち、被験食品群でプラセボ群より低値を示した期間は、全期間（プラセボ群：３．８％、被験食品群：２．５％、群間差：－１．３％［－２．０、－０．７］、Ｐ＜０．００１）、後期（プラセボ群：３．９％、被験食品群：２．０％、群間差：－１．９％［－２．８、－１．１］、Ｐ＜０．００１）であった。 (56) Proportion of muscle pain with severity level 3 Among the periods in which significant differences were observed, the periods in which the test food group showed lower values than the placebo group were the entire period (placebo group: 3.8%, test food group: 2.5%, difference between groups: -1.3% [-2.0, -0.7], P<0.001) and the late period (placebo group: 3.9%, test food group: 2.0%, difference between groups: -1.9% [-2.8, -1.1], P<0.001).
（５７）筋肉痛の重症度４の割合
　有意差が認められた期間のうち、被験食品群でプラセボ群より低値を示した期間は、全期間（プラセボ群：１．１％、被験食品群：０．６％、群間差：－０．５％［－０．８、－０．１］、Ｐ＝０．００７）、後期（プラセボ群：１．４％、被験食品群：０．５％、群間差：－０．９％［－１．４、－０．４］、Ｐ＜０．００１）であった。 (57) Proportion of muscle pain with severity level 4 Among the periods in which significant differences were observed, the periods in which the test food group showed lower values than the placebo group were the entire period (placebo group: 1.1%, test food group: 0.6%, difference between groups: -0.5% [-0.8, -0.1], P = 0.007) and the late period (placebo group: 1.4%, test food group: 0.5%, difference between groups: -0.9% [-1.4, -0.4], P < 0.001).
（５８）頭痛の重症度１の割合
　有意差が認められた期間のうち、被験食品群でプラセボ群より高値を示した期間は、全期間（プラセボ群：７８．９％、被験食品群：８５．３％、群間差：６．４％［５．０、７．８］、Ｐ＜０．００１）、前期（プラセボ群：７９．４％、被験食品群：８３．９％、群間差：４．４％［２．５、６．４］、Ｐ＜０．００１）、後期（プラセボ群：７８．３％、被験食品群：８６．７％、群間差：８．４％［６．５、１０．４］、Ｐ＜０．００１）であった。 (58) Proportion of headache severity level 1 Among the periods in which significant differences were observed, the periods in which the test food group showed higher values than the placebo group were the entire period (placebo group: 78.9%, test food group: 85.3%, difference between groups: 6.4% [5.0, 7.8], P<0.001), the early period (placebo group: 79.4%, test food group: 83.9%, difference between groups: 4.4% [2.5, 6.4], P<0.001), and the late period (placebo group: 78.3%, test food group: 86.7%, difference between groups: 8.4% [6.5, 10.4], P<0.001).
（５９）頭痛の重症度２の割合
　有意差が認められた期間のうち、被験食品群でプラセボ群より低値を示した期間は、全期間（プラセボ群：１５．７％、被験食品群：９．８％、群間差：－５．８％［－７．０、－４．７］、Ｐ＜０．００１）、前期（プラセボ群：１５．４％、被験食品群：１１．２％、群間差：－４．１％［－５．９、－２．４］、Ｐ＜０．００１）、後期（プラセボ群：１６．０％、被験食品群：８．５％、群間差：－７．６％［－９．２、－５．９］、Ｐ＜０．００１）であった。 (59) Proportion of headache severity level 2 Among the periods in which significant differences were observed, the periods in which the test food group showed lower values than the placebo group were the entire period (placebo group: 15.7%, test food group: 9.8%, difference between groups: -5.8% [-7.0, -4.7], P<0.001), the early period (placebo group: 15.4%, test food group: 11.2%, difference between groups: -4.1% [-5.9, -2.4], P<0.001), and the late period (placebo group: 16.0%, test food group: 8.5%, difference between groups: -7.6% [-9.2, -5.9], P<0.001).
（６０）頭痛の重症度３の割合
　有意差が認められた期間のうち、被験食品群でプラセボ群より低値を示した期間は、全期間（プラセボ群：４．４％、被験食品群：３．５％、群間差：－１．０％［－１．７、－０．３］、Ｐ＝０．００７）、後期（プラセボ群：４．５％、被験食品群：３．１％、群間差：－１．３％［－２．３、－０．４］、Ｐ＝０．００８）であった。 (60) Proportion of headache severity level 3 Among the periods in which significant differences were observed, the periods in which the test food group showed lower values than the placebo group were the entire period (placebo group: 4.4%, test food group: 3.5%, difference between groups: -1.0% [-1.7, -0.3], P = 0.007) and the late period (placebo group: 4.5%, test food group: 3.1%, difference between groups: -1.3% [-2.3, -0.4], P = 0.008).
＜試験のまとめ＞
　以上の結果から、ユーグレナを経口摂取することで、感冒症状を抑えることができることが示された。 <Exam Summary>
These results indicate that oral intake of Euglena can suppress cold symptoms.
　本試験の主要アウトカムである全期間における試験参加者ごとの感冒症状の累積日数の平均値と標準偏差は被験食品群が１５．９±１７．５日、プラセボ群２１．３±１９．２日であった。群間差とその９５％信頼区間は、－５．４日［－１０．４、－０．５］であり、感冒症状の累積日数は被験食品群がプラセボ群よりも有意に少なかった。 The primary outcome of this study was the mean and standard deviation of the cumulative number of days with cold symptoms for each participant over the entire period: 15.9 ± 17.5 days for the test food group and 21.3 ± 19.2 days for the placebo group. The difference between the groups and its 95% confidence interval was -5.4 days [-10.4, -0.5], meaning that the cumulative number of days with cold symptoms was significantly less in the test food group than in the placebo group.
　また、後期における疲労の累積日数においても被験食品群はプラセボ群と比較して有意に少なかった。その他の症状における累積日数においても被験食品群の方がプラセボ群よりも少なくなる兆候が散見された。 In addition, the cumulative number of days with fatigue in the later stages was significantly less in the test food group than in the placebo group. There were also some signs that the cumulative number of days with other symptoms was less in the test food group than in the placebo group.
　さらに、群ごとの感冒症状の累積日数を確認したところ、被験食品群における感冒症状の累積日数はプラセボ群と比較して、全期間、前期、後期で有意に少なく、全身倦怠感、寒気、疲労、くしゃみ、鼻汁、鼻閉、のどの痛み、せき、筋肉痛の各症状における累積日数においても、被験食品群は有意に少なかった。 Furthermore, when the cumulative number of days with cold symptoms for each group was checked, the cumulative number of days with cold symptoms in the test food group was significantly lower than in the placebo group throughout the entire period and in the early and late periods, and the cumulative number of days with each of the following symptoms was also significantly lower in the test food group: general malaise, chills, fatigue, sneezing, runny nose, nasal congestion, sore throat, cough, and muscle pain.

Claims (7)

  1. 　ユーグレナ藻体を含有する感冒症状の予防及び／又は改善用経口組成物。 An oral composition containing Euglena algae for preventing and/or improving cold symptoms.
  2. 　前記感冒症状は、全身倦怠感、寒気、熱っぽさ、疲労、くしゃみ、鼻汁、鼻閉、のどの痛み、せき、関節痛、筋肉痛、頭痛からなる群より選択される少なくとも１種である請求項１に記載の感冒症状の予防及び／又は改善用経口組成物。 The oral composition for preventing and/or improving cold symptoms according to claim 1, wherein the cold symptoms are at least one selected from the group consisting of general malaise, chills, fever, fatigue, sneezing, runny nose, nasal congestion, sore throat, cough, joint pain, muscle pain, and headache.
  3. 　鼻の不快感の軽減、鼻みずの軽減、鼻づまりの軽減、鼻の痒みの軽減、鼻のむずむず感の軽減、喉の不快感の軽減、のどの腫れの軽減、のどの赤味の軽減、のどのイガイガの軽減、声がれの軽減、たんの軽減、悪寒の軽減、ゾクゾク感の軽減、グズグズ感の軽減、ほてり感の軽減、ぼーっと感の軽減、めまいの軽減、ぐったり感の軽減、無気力感の軽減、体のだるさの軽減からなる群より選択される少なくとも１種のために用いられる請求項１に記載の感冒症状の予防及び／又は改善用経口組成物。 The oral composition for preventing and/or improving cold symptoms according to claim 1, which is used for at least one selected from the group consisting of relieving nasal discomfort, relieving runny nose, relieving nasal congestion, relieving itchy nose, relieving stuffy nose, relieving throat discomfort, relieving throat swelling, relieving redness in the throat, relieving a sore throat, relieving hoarseness, relieving phlegm, relieving chills, relieving tingling, relieving a feeling of lethargy, relieving a feeling of hot flashes, relieving a feeling of daze, relieving a feeling of lethargy, relieving a feeling of lethargy, and relieving a feeling of fatigue.
  4. 　前記ユーグレナ藻体が１日あたり５００ｍｇ以上で５週間以上継続して摂取される請求項１乃至３のいずれか一項に記載の感冒症状の予防及び／又は改善用経口組成物。 The oral composition for preventing and/or improving cold symptoms according to any one of claims 1 to 3, wherein the Euglena algae are ingested at 500 mg or more per day for 5 weeks or more.
  5. 　食品である請求項４に記載の感冒症状の予防及び／又は改善用経口組成物。 The oral composition for preventing and/or improving cold symptoms according to claim 4, which is a food product.
  6. 　飲料である請求項４に記載の感冒症状の予防及び／又は改善用経口組成物。 The oral composition for preventing and/or improving cold symptoms according to claim 4, which is a beverage.
  7. 　医薬品である請求項４に記載の感冒症状の予防及び／又は改善用経口組成物。 The oral composition for preventing and/or improving cold symptoms according to claim 4, which is a pharmaceutical product.
PCT/JP2023/034691 2022-10-13 2023-09-25 Oral composition for preventing and/or improving cold symptoms WO2024080117A1 (en)

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Citations (2)

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WO2015156339A1 (en) * 2014-04-08 2015-10-15 株式会社ユーグレナ Immune balance adjustment agent
WO2019108319A1 (en) * 2017-12-01 2019-06-06 Kemin Industries, Inc. Compositions containing euglena gracilis for viral protection and related methods

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WO2015156339A1 (en) * 2014-04-08 2015-10-15 株式会社ユーグレナ Immune balance adjustment agent
WO2019108319A1 (en) * 2017-12-01 2019-06-06 Kemin Industries, Inc. Compositions containing euglena gracilis for viral protection and related methods

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Title
ANONYMOUS: "The Definitive Midorimushi Dictionary", MIDORIMUSHI, 18 August 2022 (2022-08-18), XP093159542, Retrieved from the Internet <URL:https://midorimushi-family.jp/blog/2015/02/2108.html> *
ANONYMOUS: "The Virtues of Euglena", CADC-ALBUFEIRA, 7 October 2022 (2022-10-07), XP093159539, Retrieved from the Internet <URL:https://www.cadc-albufeira.org/management-blog/116.html> *
EUGLENA: "Continuous intake of microalgae Euglena maintain and adjust immunity Human clinical trials have confirmed that it suppresses the occurrence of cold symptoms (cold-like symptoms) and the severity of various symptoms. ", EUGLENA - PRESS RELEASE, 1 November 2022 (2022-11-01), XP093159545, Retrieved from the Internet <URL:https://euglena.jp/news/20221101-2/> *
KAWANO TAKANORI; MIURA ATSUSHI; NAITO JUNKO; NISHIDA NORIHISA; ISHIBASHI KEN-ICHI; ADACHI YOSHIYUKI; OHNO NAOHITO; NAITO YUJI: "High-parameter immune profiling and subjective health assessment of the immunomodulatory effects of paramylon-rich Euglena gracilis EOD-1: A randomized, double-blind, placebo-controlled, parallel-group study", JOURNAL OF FUNCTIONAL FOODS, ELSEVIER BV, NL, vol. 109, 23 September 2023 (2023-09-23), NL , XP087415353, ISSN: 1756-4646, DOI: 10.1016/j.jff.2023.105804 *
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