Oral composition

Abstract

The purpose of the present invention is to provide an astaxanthin compound-containing oral composition for which discoloration within the oral cavity by the astaxanthin compound is suppressed. The present invention relates to an oral composition comprising an astaxanthin compound and ergothioneine or a salt thereof.

Description

Oral Composition

[0001] The present invention relates to an oral composition. The present invention also relates to an agent for inhibiting oral discoloration caused by an astaxanthin-class compound, and use of the astaxanthin-class compound for inhibiting oral discoloration.

[0002] Astaxanthin is a type of red carotenoid that is extremely widely distributed throughout the animal kingdom, including in the shells and eggs of crustaceans, salmon flesh, and the skin of alfonsino, and is involved in the expression of flesh and body color. Astaxanthin is used as a red pigment (Patent Document 1), and due to its strong antioxidant properties, its use as a pharmaceutical active ingredient is also being investigated (Patent Document 2). Furthermore, astaxanthin has been found to have various useful effects in addition to its antioxidant properties (e.g., Patent Document 3). Therefore, astaxanthin is promising as an active ingredient in pharmaceuticals and functional foods.

[0003] Japanese Patent Application Laid-Open No. 2023-119768 Japanese Patent No. 3163127 Japanese Patent Application Laid-Open No. 9-124470 Japanese Patent Application Laid-Open No. 2017-218431

[0004] However, while the present inventors were studying oral compositions containing astaxanthin-related compounds, it became clear that when these compositions were taken into the mouth, the astaxanthin-related compounds would stain the oral cavity red.

[0005] An object of the present invention is to provide an oral composition containing an astaxanthin-class compound that suppresses oral discoloration caused by the astaxanthin-class compound.

[0006] Therefore, the present inventors conducted extensive research to solve the above problems, and as a result, they discovered that when ergothioneine or a salt thereof is added to an oral composition containing an astaxanthin-related compound, coloration of the oral cavity caused by the astaxanthin-related compound when the composition is held in the mouth is suppressed, thereby solving the above problems.

[0007] Ergothioneine is an amino acid found in mushrooms and the like, and exists naturally in the L-form. L-ergothioneine is known to have physiological effects such as antioxidant activity. Furthermore, with regard to the physiological effects of ergothioneine, for example, Patent Document 4 reports that it promotes the production of cytokines that activate immune responses. However, the inhibitory effect of ergothioneine on oral discoloration was completely unknown, and the present inventors were the first to discover that ergothioneine has the effect of inhibiting oral discoloration caused by astaxanthin-like compounds.

[0008] The present invention relates to the following oral compositions, etc.: [1] An oral composition comprising an astaxanthin-related compound and ergothioneine or a salt thereof. [2] The oral composition according to [1] above, in which the ratio of the astaxanthin-equivalent weight of the astaxanthin-related compound to the ergothioneine-equivalent weight of the ergothioneine or salt thereof (astaxanthin-equivalent weight of the astaxanthin-related compound / ergothioneine-equivalent weight of the ergothioneine or salt thereof) is 15 or less. [3] The oral composition according to [1] or [2] above, in which oral discoloration caused by the astaxanthin-related compound is suppressed. [4] The oral composition according to any of [1] to [3] above, in which the astaxanthin-related compound is at least one compound selected from the group consisting of astaxanthin and derivatives thereof. [5] The oral composition according to any of [1] to [4] above, in which the content of the astaxanthin-related compound is 0.03% by weight or more in terms of astaxanthin. [6] The oral composition according to any one of [1] to [5], wherein the oral composition is in the form of a capsule, tablet, coated tablet, fine granule, granule, powder, pill, dry syrup, chewable tablet, jelly, or gummy. [7] An agent for inhibiting oral discoloration caused by an astaxanthin-related compound, comprising ergothioneine or a salt thereof. [8] Use of ergothioneine or a salt thereof for inhibiting oral discoloration caused by an astaxanthin-related compound.

[0009] According to the present invention, it is possible to provide an oral composition containing an astaxanthin-class compound that suppresses oral discoloration caused by the astaxanthin-class compound. When the oral composition containing the astaxanthin-class compound of the present invention is orally ingested, for example, when a tablet containing the astaxanthin-class compound is placed in the mouth or when the composition is consumed as a beverage, oral discoloration caused by the astaxanthin-class compound is suppressed, and the composition can be ingested safely without causing concerns about the appearance of the person who ingests it.

[0010] The oral composition of the present invention contains an astaxanthin-class compound and ergothioneine or a salt thereof. In the present invention, the oral composition refers to an orally ingested composition and an oral composition applied to the oral cavity. Examples of oral compositions include a mouthwash composition for oral care (oral care), and a mouthwash composition that is spat out after rinsing the oral cavity is also an embodiment of the oral composition of the present invention. The oral composition of the present invention is preferably an orally ingested composition. The oral composition of the present invention is a composition that suppresses oral discoloration caused by astaxanthin-class compounds. By containing ergothioneine or a salt thereof, the oral composition of the present invention can suppress oral discoloration caused by astaxanthin-class compounds compared to a composition that does not contain ergothioneine or a salt thereof. Oral discoloration caused by astaxanthin-class compounds refers to red discoloration of the oral cavity caused by astaxanthin-class compounds that occurs when the astaxanthin-class compounds come into contact with the oral cavity, such as the tongue. The oral composition of the present invention is preferably a composition that suppresses tongue discoloration caused by astaxanthin-class compounds. The mechanism by which the inclusion of ergothioneine or a salt thereof in the oral composition of the present invention can suppress oral discoloration caused by astaxanthin-related compounds has not been clarified, but the same effect cannot be obtained when other powdery substances are added to astaxanthin-related compounds, and this is thought to be an effect unique to ergothioneine or a salt thereof.

[0011] (Astaxanthin Compounds) In the present invention, the term "astaxanthin compound" refers collectively to compounds containing astaxanthin and its derivatives. The astaxanthin compound may be a single compound or two or more compounds. Astaxanthin (3,3'-dihydroxy-β,β-carotene-4,4'-dione) is a type of carotenoid, a red pigment found in crustaceans such as shrimp and crab, fish such as salmon and sea bream, algae such as the green algae Haematococcus, and yeasts such as the red yeast Phaffia. Astaxanthin exists in three isomers, the 3S,3'S form, the 3S,3'R form (meso form), and the 3R,3'R form, depending on the configuration of the hydroxyl groups at the 3 (3') positions of the ring structures at both ends of the molecule. Furthermore, geometric isomers, such as cis and trans configurations of the conjugated double bond at the center of the molecule, also exist. Specific examples of geometric isomers include all-trans isomers, 9-cis isomers, and 13-cis isomers. Astaxanthin may be any one of these compounds, or two or more of these compounds.

[0012] The astaxanthin derivative is not particularly limited, and may be any compound in which a substituent or the like is bonded to a functional group possessed by astaxanthin, such as an ester. The hydroxyl group at the 3 (3') position of astaxanthin can form an ester with a fatty acid, and astaxanthin esters include monoesters and diesters. Hydrolysis of an astaxanthin ester produces astaxanthin. The fatty acid that forms the ester is not particularly limited, but the number of carbon atoms in the fatty acid is preferably 1 to 30. In the present invention, the astaxanthin-like compound is preferably astaxanthin, an astaxanthin ester, or a combination thereof.

[0013] The astaxanthin compound used in the present invention is not limited in any way by its form or production method. Natural astaxanthin compounds and synthetic astaxanthin compounds can be used. Examples of natural astaxanthin compounds include those derived from algae such as Haematococcus; yeasts such as Phaffia; crustaceans such as shrimp, krill, and crab; cephalopods such as squid and octopus; various seafood; plants such as Adonis; bacteria such as Paracoccus sp. N81106, Brevundimonas sp. SD212, and Erythrobacter sp. PC6; actinomycetes such as Gordonia sp. KANMONKAZ-1129; and Schizochytriuym sp. Examples of astaxanthin-related compounds include astaxanthin-related compounds derived from microorganisms, plants, seafood, etc., such as Labyrinthulea species such as KH105; fungi such as Blakeslea trispora; and astaxanthin-producing genetically modified organisms. In the present invention, for example, an astaxanthin-related compound-containing extract obtained by extraction from the above-mentioned microorganisms, plants, seafood, etc. using a known method can be used to incorporate the astaxanthin-related compound into an oral composition. Alternatively, an astaxanthin-related compound appropriately purified from the above-mentioned astaxanthin-related compound-containing extract may be incorporated into an oral composition. The astaxanthin-related compound is preferably an astaxanthin-related compound derived from a microalgae extract extracted from microalgae such as Haematococcus, or an astaxanthin-related compound derived from a fungal extract extracted from fungi such as Blakeslea trispora, and more preferably an astaxanthin-related compound derived from a Haematococcus algae extract extracted from Haematococcus algae. Examples of synthetic astaxanthin-related compounds include AstaSana (DSM) and Lucantin Pink (registered trademark) (BASF). Examples of synthetic astaxanthin-related compounds obtained by chemically converting other naturally occurring carotenoids include AstaMarine (PIVEG).

[0014] Examples of Haematococcus algae from which astaxanthin compounds can be obtained include Haematococcus pluvialis, Haematococcus lacustris, Haematococcus capensis, Haematococcus deroebakensis, and Haematococcus zimbabwiensis.

[0015] The method for culturing the above-mentioned Haematococcus algae is not particularly limited, but a sealed culture method is preferred, which does not introduce or grow foreign microorganisms and is less likely to introduce other contaminants. Examples of such culture methods include a culture method using a partially open dome-shaped, conical, or cylindrical culture device and a culture medium having a gas discharge device that can be moved freely within the device (WO 1999 / 050384), a method in which Haematococcus algae are subjected to desiccation stress to induce encystment of the algae and astaxanthin is collected from a culture of the encysted algae (JP 8-103288 A), a method in which a light source is placed in a sealed culture device and light is irradiated from the inside to carry out culture, and a method using a flat culture tank or a tubular culture layer.

[0016] The astaxanthin-related compounds that can be used in the present invention may be, for example, an astaxanthin-related compound-containing extract obtained by disrupting the cell walls of the above-mentioned Haematococcus algae, if necessary, according to the method disclosed in JP-A-5-068585, and then adding an extraction solvent or solvent such as acetone, ether, chloroform, or alcohol (ethanol, methanol, etc.), or supercritical carbon dioxide, or this astaxanthin-related compound-containing extract may be appropriately purified as necessary and then incorporated into the composition. The astaxanthin-related compound content of the astaxanthin-related compound-containing extract is preferably 3 to 40 wt%, more preferably 3 to 12 wt%, and even more preferably 5 to 10 wt%.

[0017] In the present invention, commercially available products can also be used as the astaxanthin-related compounds or extracts containing the same, such as AstaReal Oil 200SS (a fat-soluble extract from Haematococcus algae, containing approximately 20% astaxanthin-related compounds in terms of free form (astaxanthin)), AstaReal L10, AstaReal Oil 50F, AstaReal Oil 50FC, AstaReal Oil 5F, and AstaReal AstaReal, Astavita, and Astamate series such as P2AF, AstaTROL-X, AstaReal Oil 50FC, AstaReal Powder 20F, Water-soluble AstaReal Liquid, AstaReal WS Liquid, AstaReal 10WS Liquid, AstaReal ACT, Astavita e, Astavita Sports, and Astamate (all registered trademarks; manufactured by AstaReal Co., Ltd. and Fuji Chemical Industry Co., Ltd.); ASTOTS series such as ASTOTS-S, ASTOTS-10O, ASTOTS-ECS, ASTPTS-2.0PW, and ASTOTS-3.0MB (all ASTOTS are registered trademarks; manufactured by Fujifilm Wako Pure Chemical Industries Co., Ltd.); BioAstin (registered trademark; manufactured by Cyanotec Corporation); Astazine™ (BGG Examples of suitable astaxanthin extracts include astaxanthin powder 1.5%, astaxanthin powder 2.5%, astaxanthin oil 5%, and astaxanthin oil 10% (manufactured by Bioactives Japan); astaxanthin (manufactured by Oryza Oil & Fat Chemical Co., Ltd.); Sunactive AX (registered trademark; manufactured by Taiyo Kagaku Co., Ltd.); Haematococcus WS30 (manufactured by Yaegaki Fermentation Engineering Co., Ltd.); and AstaMarine (manufactured by PIVEG).

[0018] (Ergothioneine or Salt Thereof) Ergothioneine is a type of sulfur-containing amino acid. The salt of ergothioneine is not particularly limited as long as it is a pharmacologically acceptable salt or a salt acceptable for use in foods and beverages, and may be either an acid salt or a basic salt. Examples of acid salts include inorganic acid salts such as hydrochloride, sulfate, nitrate, and phosphate; and organic acid salts such as acetate, citrate, maleate, malate, oxalate, lactate, succinate, fumarate, and propionate. Examples of basic salts include alkali metal salts such as sodium salt and potassium salt; and alkaline earth metal salts such as calcium salt and magnesium salt.

[0019] Ergothioneine or a salt thereof is not limited in any way by its form, production method, etc. Ergothioneine or a salt thereof may be a chemically synthesized product, or may be extracted and purified from a natural product. Ergothioneine is contained in large amounts in the Golden / Yellow Oyster Mushroom (scientific name: Pleurotus cornucopiae var. citrinopileatus), a mushroom of the Pleurotus genus in the family Pleurotus. Ergothioneine is found in mushrooms such as white button mushrooms, crimini mushrooms, and portabella mushrooms (Agaricus bisporus), Grey Oyster Mushrooms (Pleurotus ostreatus), shiitake mushrooms (Lentinula edodes), Maitake mushrooms (Grifola frondosa), reishi mushrooms (Ganoderma lucidum), Yamabushitake mushrooms (Hericium erinaceus), Yanagimatsutake mushrooms (Agrocybe aegerita), and chanterelle mushrooms (Cantharella verruca). Ergothioneine is also found in mushrooms such as mushrooms like Pleurotus civarius, porcini mushroom (scientific name: Boletus edulis), and morel mushroom (scientific name: Morchella esculenta). When obtaining ergothioneine from a natural product, it is preferable to extract it from Pleurotus cornucopiae. Ergothioneine or a salt thereof can also be produced by microbial fermentation. Ergothioneine or a salt thereof may be isolated. Since ergothioneine exists in large amounts in the L-isomer in nature, the ergothioneine or a salt thereof used in the oral composition of the present invention is preferably L-ergothioneine or a salt thereof.

[0020] Ergothioneine or a salt thereof is a compound that is found in natural products and foods and beverages and has been consumed as a dietary source. Therefore, from the viewpoint of safety, ergothioneine or a salt thereof is thought to pose few problems, even when taken over a long period of time.

[0021] In the oral composition of the present invention, the ratio of the astaxanthin-equivalent weight of the astaxanthin-class compound to the ergothioneine-equivalent weight of ergothioneine or a salt thereof (astaxanthin-equivalent weight of the astaxanthin-class compound / ergothioneine-equivalent weight of the ergothioneine or a salt thereof) is preferably 15 or less. This is because, when the weight ratio in the oral composition (astaxanthin-equivalent weight of the astaxanthin-class compound / ergothioneine-equivalent weight of the ergothioneine or a salt thereof) is 15 or less, oral coloration caused by the astaxanthin-class compound can be effectively suppressed. The weight ratio in the oral composition (astaxanthin-equivalent weight of the astaxanthin-class compound / ergothioneine-equivalent weight of the ergothioneine or a salt thereof) is more preferably 10 or less, even more preferably 6 or less, particularly preferably 4 or less, and most preferably 3.75 or less. The weight ratio (weight of astaxanthin-related compound in terms of astaxanthin / weight of ergothioneine or a salt thereof in terms of ergothioneine) in the oral composition is preferably 0.01 or more, more preferably 0.1 or more, and even more preferably 0.5 or more. In one aspect, the weight ratio (weight of astaxanthin-related compound in terms of astaxanthin / weight of ergothioneine or a salt thereof in terms of ergothioneine) in the oral composition is preferably 0.01 to 15, more preferably 0.1 to 10, even more preferably 0.1 to 6, even more preferably 0.1 to 4, and particularly preferably 0.5 to 3.75. When two or more types of astaxanthin-related compounds are used, the weight of the astaxanthin-related compound refers to the total weight of these compounds. When two or more types of ergothioneine or a salt thereof are used, the weight of ergothioneine or a salt thereof refers to the total weight of these compounds.

[0022] In this specification, the term "astaxanthin equivalent" refers to the value converted into astaxanthin when the astaxanthin-related compound is a compound other than astaxanthin. More specifically, in this specification, the "astaxanthin-equivalent amount" or similar expressions refer to the amount of astaxanthin when the astaxanthin-related compound is astaxanthin, and when the astaxanthin-related compound is a compound other than astaxanthin, refer to the value obtained by multiplying the number of moles of the compound by the molecular weight of astaxanthin. The content of the astaxanthin-related compound in the composition can be measured by HPLC (high performance liquid chromatography). In addition, when the astaxanthin-related compound is a derivative of astaxanthin, it can be quantified as astaxanthin by performing a process such as hydrolysis.

[0023] In this specification, "ergothioneine equivalent" refers to the value converted to ergothioneine when ergothioneine is a salt of ergothioneine. More specifically, in this specification, "ergothioneine equivalent amount" or similar expressions refer to the amount of ergothioneine or its salt when it is ergothioneine, and when it is an ergothioneine salt, refer to the value obtained by multiplying the number of moles of the salt by the molecular weight of ergothioneine. The content of ergothioneine or its salt can be measured by HPLC (high performance liquid chromatography).

[0024] The content of the astaxanthin-class compound (astaxanthin equivalent) contained in the oral composition of the present invention is not particularly limited and can be set depending on the form, etc. The content of the astaxanthin-class compound in the oral composition of the present invention may be, for example, 0.001 wt % or more in terms of astaxanthin, preferably greater than 0.02 wt %, more preferably 0.03 wt % or more, even more preferably 0.05 wt % or more, and preferably 10 wt % or less, more preferably 5 wt % or less. In one embodiment, the content of the astaxanthin-class compound in the oral composition may be 0.001 to 10 wt %, preferably greater than 0.02 wt % to 10 wt %, more preferably 0.03 to 10 wt %, and even more preferably 0.05 to 5 wt %. The content of the astaxanthin-class compound in the oral composition of the present invention (astaxanthin equivalent) can be within a range that appropriately combines the above-mentioned preferred lower and upper limits depending on the form of the composition.

[0025] The content of ergothioneine or a salt thereof contained in the oral composition of the present invention is not particularly limited and can be set depending on the form, etc. The content of ergothioneine or a salt thereof contained in the oral composition of the present invention, in terms of ergothioneine, is, for example, preferably 0.0001 wt% or more, more preferably 0.001 wt% or more, even more preferably 0.002 wt% or more, particularly preferably 0.003 wt% or more, and preferably 90 wt% or less, more preferably 50 wt% or less. In one aspect, the content of ergothioneine or a salt thereof contained in the oral composition of the present invention, in terms of ergothioneine, is preferably 0.0001 to 90 wt%, more preferably 0.001 to 50 wt%, even more preferably 0.002 to 50 wt%, and particularly preferably 0.003 to 50 wt%. The content of ergothioneine or a salt thereof in the oral composition of the present invention (in terms of ergothioneine) can be within a numerical range that appropriately combines the above-mentioned preferred lower and upper limits depending on the form of the composition.

[0026] The oral composition of the present invention is a composition in which discoloration of the oral cavity caused by astaxanthin-related compounds is suppressed. Therefore, the oral composition of the present invention does not include natural foods such as shells and eggs of crustaceans, salmon meat, and the skin of alfonsino, which do not cause discoloration of the oral cavity caused by astaxanthin-related compounds.

[0027] The oral composition of the present invention can be provided in the form of, for example, a food or drink, a pharmaceutical product, a quasi-drug, a feed, etc., but is not limited thereto. The oral composition of the present invention can contain any additives and any components in addition to the above-mentioned astaxanthin-class compound and ergothioneine or a salt thereof, as long as the effects of the present invention are not impaired. These additives and components can be selected depending on the form of the composition, and those that can generally be used in oral compositions such as a food or drink, a pharmaceutical product, a quasi-drug, and a feed can be used. In one aspect, the oral composition of the present invention may consist of an astaxanthin-class compound and ergothioneine or a salt thereof.

[0028] The form of the oral composition of the present invention is not particularly limited and may be a solid (powder, granules, tablets, gel, etc.), a liquid, etc., and is preferably a solid. In one embodiment, the oral composition of the present invention is preferably a solid oral composition. The oral composition of the present invention may be in the form of, for example, a capsule (soft capsule, hard capsule), a tablet, a coated tablet, fine granules, granules, powder, pill, dry syrup, chewable agent, jelly, gummy, etc.

[0029] In one embodiment, when the oral composition of the present invention is an orally ingested composition, the form of the orally ingested composition is not particularly limited and may be a solid (powder, granules, tablet, gel, etc.), a liquid, etc., and is preferably a solid. The orally ingested composition is preferably a solid orally ingested composition, and may be in the form of, for example, a capsule (soft capsule, hard capsule), a tablet, a coated tablet, fine granules, granules, powder, pills, dry syrup, chewable tablets, jelly, gummies, etc. In addition, in one embodiment, when the oral composition of the present invention is an oral composition, the oral composition may be in the form of a paste, liquid, gum, etc.

[0030] Astaxanthin-class compounds are fat-soluble. In one aspect, the oral composition of the present invention is preferably dissolved, emulsified, or dispersed in edible oil, from the viewpoint of efficient intake of the astaxanthin-class compounds. From this viewpoint, it is also preferable that the oral composition of the present invention contains edible oil. As the edible oil, one capable of dissolving the astaxanthin-class compounds is preferred, and examples thereof include MCT oil, soybean oil, rapeseed oil, safflower oil, olive oil, and palm oil. The edible oil may be one type, or two or more types.

[0031] The oral composition of the present invention preferably contains at least one selected from the group consisting of an emulsifier, an antioxidant, and a thickener. Note that, in the present invention, the antioxidant does not include astaxanthin-related compounds and ergothioneine or a salt thereof.

[0032] The oral composition of the present invention preferably contains an antioxidant, which makes the astaxanthin-class compound more stable. Examples of antioxidants include vitamin C, vitamin E, BHT, BHA, sodium erythorbate, propyl gallate, sodium sulfite, potassium sulfite, potassium pyrosulfite, sulfur dioxide, etc., and the antioxidant may be one type or two or more types.

[0033] When the oral composition of the present invention is prepared as a food or beverage, various foods and beverages can be prepared by blending the astaxanthin-class compound and ergothioneine or a salt thereof with ingredients usable in foods and beverages (e.g., food and beverage ingredients, additives used as needed, etc.). The foods and beverages are not particularly limited, and examples thereof include general foods and beverages, health foods, food additives, and the raw materials thereof. The form of the foods and beverages is also not particularly limited, and examples thereof include solid, semi-liquid, and liquid forms. When the oral composition of the present invention is a food or beverage, it can be in the form of, for example, a solid form such as a capsule (soft capsule, hard capsule), tablet, coated tablet, fine granules, granules, powder, pill, dry syrup, chewable tablet, jelly, or gummy; or a liquid form such as an oral liquid or syrup, preferably a solid form. When the oral composition of the present invention is a food or beverage, its form is preferably a capsule (soft capsule, hard capsule), tablet, coated tablet, fine granules, granules, powder, pill, dry syrup, chewable tablet, jelly, or gummy.

[0034] When the oral composition of the present invention is used as a pharmaceutical or quasi-drug, it can be formulated with an astaxanthin-class compound, ergothioneine or a salt thereof, and pharmacologically acceptable excipients to produce a pharmaceutical in various dosage forms. The dosage form may be a dosage form for oral administration. Examples of dosage forms for oral pharmaceuticals include oral solid preparations such as capsules (soft capsules, hard capsules), tablets, coated tablets, fine granules, granules, powders, pills, dry syrup, chewable tablets, and gummies; oral gel preparations such as jellies; and oral liquid preparations such as oral liquids and syrups. When the oral composition of the present invention is a pharmaceutical or quasi-drug, its form is preferably a capsule (soft capsules, hard capsules), tablets, coated tablets, fine granules, granules, powders, pills, dry syrup, chewable tablets, jellies, or gummies.

[0035] When the oral composition of the present invention is used as feed, in addition to the astaxanthin-class compound and ergothioneine or a salt thereof, ingredients usable in feed can be blended to prepare the feed. Examples of feed include livestock feed used for cattle, pigs, chickens, sheep, horses, etc.; small animal feed used for rabbits, guinea pigs, rats, mice, etc.; and pet food used for dogs, cats, small birds, etc. When the oral composition of the present invention is used as feed, its form is preferably a capsule (soft capsule, hard capsule), tablet, coated tablet, fine granule, granule, powder, pill, dry syrup, chewable agent, jelly, or gummy.

[0036] When the oral composition of the present invention is a solid composition such as a capsule (soft capsule, hard capsule), tablet, coated tablet, fine granule, granule, powder, pill, dry syrup, chewable jelly, or gummy candy, the content of the astaxanthin-class compound (astaxanthin equivalent) may be, for example, 0.001 wt% or more, preferably greater than 0.02 wt%, more preferably 0.03 wt% or more, and even more preferably 0.05 wt% or more. Also, 10 wt% or less is preferred, and 5 wt% or less is more preferred. In one embodiment, when the oral composition is solid, the content of the astaxanthin-class compound contained in the composition (astaxanthin equivalent) may be 0.001 to 10 wt%, preferably greater than 0.02 wt% to 10 wt% or less, more preferably 0.03 to 10 wt%, and even more preferably 0.05 to 5 wt%.

[0037] When the oral composition of the present invention is used in the form of a food or drink, a pharmaceutical product, a quasi-drug, a feed, etc., the method for producing it is not particularly limited, and it can be produced by a general method using an astaxanthin-class compound and ergothioneine or a salt thereof. In producing the oral composition of the present invention, purified compounds may be used as the astaxanthin-class compound, ergothioneine, or a salt thereof, or raw materials derived from animals, plants, or microorganisms that are rich in astaxanthin-class compounds, or raw materials derived from plants or microorganisms that are rich in ergothioneine or a salt thereof may be used.

[0038] In one embodiment, when the oral composition of the present invention is ingested or administered to a human (adult) subject, the total dosage of astaxanthin-related compounds is preferably 0.5 to 200 mg, more preferably 1 to 100 mg, and even more preferably 3 to 80 mg, in terms of astaxanthin per 60 kg of body weight per day. When the composition contains two or more astaxanthin-related compounds, the total dosage of the astaxanthin-related compounds is the total amount of these compounds.

[0039] In one embodiment, when the oral composition of the present invention is ingested or administered to a human (adult) subject, the total dose of ergothioneine or a salt thereof is preferably 0.03 to 100 mg, more preferably 0.07 to 100 mg, and even more preferably 0.2 to 80 mg, in terms of ergothioneine, per 60 kg of body weight per day.

[0040] The subject to which the oral composition of the present invention is ingested or administered (also referred to as the administration subject) is not particularly limited, and examples thereof include humans and non-human animals. The administration subject to which the oral composition of the present invention is administered is preferably a human or a non-human mammal, and more preferably a human.

[0041] The present invention also encompasses an agent for inhibiting oral discoloration caused by an astaxanthin-related compound, which agent contains ergothioneine or a salt thereof. The agent for inhibiting oral discoloration caused by an astaxanthin-related compound of the present invention is used to inhibit oral discoloration caused by an astaxanthin-related compound.

[0042] The present invention also encompasses the use of ergothioneine or a salt thereof to inhibit oral discoloration caused by astaxanthin-like compounds.

[0043] In the above-mentioned oral discoloration inhibitor using an astaxanthin-class compound, and in its use, the preferred embodiments of the astaxanthin-class compound and ergothioneine or a salt thereof are the same as those in the oral composition of the present invention described above. For example, by mixing ergothioneine or a salt thereof with an astaxanthin-class compound or an oral composition containing the same, oral discoloration caused by the astaxanthin-class compound can be suppressed when the oral composition is orally ingested. The preferred amount of ergothioneine or a salt thereof used, and the preferred embodiments of the ratio, content, etc. in the oral composition of the present invention described above are the same as those in the oral composition of the present invention described above. For example, ergothioneine or a salt thereof is used so that the ratio of the weight of the astaxanthin-based compound in terms of astaxanthin to the weight of the ergothioneine-based compound of ergothioneine or a salt thereof (weight of the astaxanthin-based compound in terms of astaxanthin / weight of the ergothioneine or a salt thereof in terms of ergothioneine) is preferably 0.01 to 15, more preferably 0.1 to 10, even more preferably 0.1 to 6, even more preferably 0.1 to 4, and particularly preferably 0.5 to 3.75.

[0044] In this specification, a numerical range expressed by a lower limit and an upper limit, i.e., "lower limit to upper limit," includes the lower limit and the upper limit. For example, a range expressed by "1 to 2" means 1 or more and 2 or less, including 1 and 2. In this specification, the upper limit and the lower limit may be any combination of ranges.

[0045] The present invention will be described in more detail below with reference to examples, although the present invention is not limited to these examples.

[0046] The astaxanthin raw material, ergothioneine raw material, dextrin raw material, cellulose raw material, and MCT oil used in the tests below are as follows: Astaxanthin raw material: Oil containing 5% astaxanthin Ergothioneine raw material: Powder, 100% L-ergothioneine purity Dextrin raw material: Powder, 100% dextrin Cellulose raw material: Powder, 100% cellulose MCT oil: Manufactured by Nisshin Oillio Co., Ltd. In the tests below, the astaxanthin raw material, oil containing 5% astaxanthin, was taken out of the refrigerator, returned to room temperature, heated to 40-50°C, and then returned to room temperature again. The ergothioneine raw material was a powder raw material returned to room temperature. The astaxanthin raw material is an oil material obtained by directly diluting Haematococcus (algae) extract, and is a raw material with an astaxanthin-related compound content (astaxanthin equivalent) of 5.0% by weight.

[0047] <Test to evaluate the suppression of oral discoloration by astaxanthin from ergothioneine> <Comparative Example 1> (Sample 1: Astaxanthin raw material) 10 mg of the astaxanthin raw material was weighed out, and 990 mg of MCT oil was weighed out and added to this so that the concentration of astaxanthin-related compounds was 0.5 mg / g in terms of astaxanthin, and mixed to obtain Sample 1 (1000 mg). The content of astaxanthin-related compounds in Sample 1 was 0.05 wt % in terms of astaxanthin.

[0048] Example 1 (Sample 2: Astaxanthin Raw Material and Ergothioneine Raw Material) 10 mg of astaxanthin raw material was weighed out, and 990 mg of MCT oil was weighed out and added to the mixture so that the concentration of astaxanthin-related compounds was 0.5 mg / g in terms of astaxanthin. Next, 0.83 mg of ergothioneine raw material was weighed out. The mixture of astaxanthin raw material and MCT oil (1000 mg) obtained above and ergothioneine raw material (0.83 mg) were thoroughly mixed on a spoon using a spatula to obtain Sample 2 (1000.83 mg). The content of astaxanthin-related compounds in Sample 2 was 0.05 wt % in terms of astaxanthin, and the content of ergothioneine was 0.083 wt %. The ratio of the weight of the astaxanthin-class compounds (equivalent to astaxanthin) to the weight of ergothioneine in Sample 2 (ataxanthin / ergothioneine) was 0.6.

[0049] (Evaluation of Coloring) Panelists placed the prepared samples on their tongues to evaluate the coloring of the oral cavity caused by astaxanthin-based compounds. For the evaluation, the entire amount of the prepared sample (e.g., 1000 mg of Sample 1) was placed on the tongue. Specifically, three panelists placed a room-temperature sample (Sample 1 or Sample 2) in a spoon on the upper part of their tongues in their oral cavity, stroked the surface of the upper part of their tongue with the bottom of the spoon to spread the sample over the entire surface, then closed their mouths and moved their tongues for 10 seconds to distribute the sample throughout their oral cavity. Next, they took 50 mL of water into their oral cavity and gargled for mouthwash. During gargling, 50 mL of water was taken into the mouth at once, and with the mouths closed, participants alternately puffed and returned their cheeks 10 times to rinse the oral cavity, after which they spat out the water. Taking 50 mL of water into the mouth, rinsing, and spitting it out constituted one gargle. After gargling once, the tongue was observed with a mirror. If red discoloration was observed in 10% or more of the entire area of ​​the upper tongue, it was evaluated as "Good", if it was observed in 10% or less of the entire area, it was evaluated as "Good", and if it was not observed at all, it was evaluated as "Poor". If the evaluation was "Good" or "Good", the subject gargled once again in the same manner as above, and then the tongue was observed with a mirror and evaluated in the same manner. The above-mentioned gargling with 50 mL of water and the subsequent evaluation of tongue discoloration were repeated until no red discoloration was observed on the upper tongue (until the evaluation was "Poor").

[0050] The test results for Samples 1 and 2 are shown in Table 1 below. The staining suppression effect was evaluated based on the total number of gargles until the tongue staining disappeared and the total score shown in the table. The fewer the total number of gargles, the more the tongue staining caused by the astaxanthin-based compounds was suppressed. The total score in the table is calculated for each panelist by assigning 2 points for "Good," 1 point for "Average," and 0 point for "Poor." This total score indicates the degree of tongue staining, and the smaller the total score, the more the tongue staining caused by the astaxanthin-based compounds was suppressed. For example, for Sample 1, Panelist 1 gargled once and scored 2 points for "Good," gargled twice and scored 1 point for "Average," and scored 0 points for "Poor" after gargling three times. Therefore, panelist 1 gargled a total of three times in the evaluation of sample 1, and received a total score of one "Good" (2 points), one "Average" (1 point), and one "Poor" (0 point), for a total of three points. The average of the total number of gargles and total scores of the three panelists was calculated. "Ast / Erg (weight ratio)" in Tables 1 to 4 indicates the ratio of the weight of the astaxanthin-based compound (Ast) to the weight of ergothioneine (Erg) in the sample, calculated as astaxanthin.

[0051]

[0052] As shown in Table 1, for all panelists, oral discoloration caused by the astaxanthin-related compound in Sample 2, which contained an ergothioneine ingredient, was more easily removed than oral discoloration caused by the astaxanthin-related compound in Sample 1. The "Erg-induced discoloration suppression rate" in Table 1 above is the calculated value for each panelist, calculated by dividing the total number of gargles in Example 1 by the total number of gargles in Comparative Example 1 and the total score for Example 1 by the total score for Comparative Example 1. Since both values ​​are less than 1, this indicates that oral discoloration caused by the astaxanthin-related compound in Example 1, which contains an ergothioneine ingredient, is suppressed. Although the degree of tongue discoloration caused by the astaxanthin-related compound varied among panelists, this is due to differences between individuals. Therefore, the effect of suppressing tongue discoloration caused by astaxanthin-related compounds was confirmed by calculating the discoloration suppression rate for the same panelist (e.g., Panelist A) comparing tongue discoloration caused by Sample 1 in Comparative Example 1 with that caused by Sample 2 in Example 1. The same applies to the following examples.

[0053] Comparative Example 2 (Sample 3: Astaxanthin Raw Material Only) 120 mg of the astaxanthin raw material was weighed out and used as Sample 3.

[0054] Example 2 (Sample 4: Astaxanthin Raw Material and Ergothioneine Raw Material) 120 mg of astaxanthin raw material was weighed out. 10 mg of ergothioneine raw material was weighed out. The astaxanthin raw material (120 mg) and ergothioneine raw material (10 mg) were thoroughly mixed on a spoon using a spatula to obtain Sample 4 (130 mg). The content of astaxanthin-related compounds in Sample 4 was 4.6 wt% in terms of astaxanthin, and the content of ergothioneine was 7.7 wt%. The ratio of the weight of astaxanthin-related compounds (astaxanthin equivalent) to the weight of ergothioneine in Sample 4 (astaxanthin / ergothioneine) was 0.6.

[0055] The coloring evaluation was carried out for the obtained Samples 3 and 4 by three panelists in the same manner as in Example 1, except that the experiment was carried out with N=3. The obtained results are shown in Table 2 below.

[0056]

[0057] As shown in Table 2, for all panelists, oral discoloration caused by the astaxanthin-class compound of Example 2, which contains an ergothioneine raw material, was more easily removed than oral discoloration caused by the astaxanthin-class compound of Comparative Example 2. The "Erg-induced discoloration suppression rate" in Table 2 above is the calculated value for each panelist: "total number of gargles in Example 2 / total number of gargles in Comparative Example 2" and "total score for Example 2 / total score for Comparative Example 2." Both values ​​are significantly below 1, indicating that oral discoloration caused by the astaxanthin-class compound of Example 2, which contains an ergothioneine raw material, is suppressed.

[0058] Comparative Example 3 (Sample 5: Astaxanthin Raw Material) 120 mg of the astaxanthin raw material was weighed out and used as Sample 5.

[0059] Example 3 (Sample 6: Astaxanthin raw material and ergothioneine raw material) 120 mg of astaxanthin raw material was weighed out. 1.0 mg of ergothioneine raw material was weighed out. These were mixed well on a spoon using a spatula to obtain Sample 6 (121 mg). The content of astaxanthin-related compounds in Sample 6 was 5.0 wt% in terms of astaxanthin, and the content of ergothioneine was 0.83 wt%. The ratio of the weight of the astaxanthin-related compounds (astaxanthin equivalent) to the weight of the ergothioneine in Sample 6 (astaxanthin / ergothioneine) was 6.

[0060] The obtained samples 5 and 6 were subjected to the above coloration evaluation in the same manner as in Example 1. The obtained results are shown in Table 3 below.

[0061]

[0062] As shown in Table 3, for all panelists, oral discoloration caused by the astaxanthin-related compound of Example 3 containing an ergothioneine source was more easily removed than oral discoloration caused by the astaxanthin-related compound of Comparative Example 3. The "Erg-induced discoloration suppression rate" in Table 3 above is calculated for each panelist by dividing the total number of gargles in Example 3 by the total number of gargles in Comparative Example 3 and the total score for Example 3 by the total score for Comparative Example 3. Both values ​​are significantly below 1, indicating that oral discoloration caused by the astaxanthin-related compound of Example 3, which contains an ergothioneine source, is sufficiently suppressed. Note that in Tables 2 and 3 above, Sample 3 in Comparative Example 2 and Sample 5 in Comparative Example 3 contain the same amount of astaxanthin-related compound and astaxanthin concentration, but the total number of gargles and the total score for each panelist are different. This difference is due to changes in the condition of each panelist's tongue depending on the test day and time of the test. Therefore, to confirm the effectiveness of astaxanthin-related compounds in suppressing tongue discoloration in this test, we compared the results of tests conducted on the same panelists at the same time on the same day. The same was true for other tests.

[0063] Comparative Example 4 (Sample 7: Astaxanthin Raw Material) 300 mg of the astaxanthin raw material was weighed out and used as Sample 7.

[0064] Example 4 (Sample 8: Astaxanthin Raw Material and Ergothioneine Raw Material) 300 mg of astaxanthin raw material was weighed out. 1.0 mg of ergothioneine raw material was weighed out. These were mixed well on a spoon using a spatula to obtain Sample 8 (400 mg). The content of astaxanthin-related compounds in Sample 8 was 5.0 wt% in terms of astaxanthin, and the content of ergothioneine was 0.33 wt%. The ratio of the weight of the astaxanthin-related compounds (astaxanthin equivalent) to the weight of the ergothioneine in Sample 8 (astaxanthin / ergothioneine) was 15.

[0065] The obtained samples 7 and 8 were subjected to the above coloration evaluation in the same manner as in Example 1. The obtained results are shown in Table 4 below.

[0066]

[0067] As shown in Table 4, for all panelists, oral discoloration caused by the astaxanthin-class compound of Example 4, which contains an ergothioneine raw material, was more easily removed than oral discoloration caused by the astaxanthin-class compound of Comparative Example 4. The "Erg-induced discoloration suppression rate" in Table 4 above is the value calculated for each panelist by dividing the "total number of gargles in Example 4 / total number of gargles in Comparative Example 4" and the "total score for Example 4 / total score for Comparative Example 4." Both values ​​are below 1, indicating that oral discoloration caused by the astaxanthin-class compound of Example 4, which contains an ergothioneine raw material, is suppressed.

[0068] Comparative Example 5 (Sample 9: Astaxanthin Raw Material Only) 120 mg of the astaxanthin raw material was weighed out and used as Sample 9.

[0069] Comparative Example 6 (Sample 10: Astaxanthin Raw Material and Dextrin Raw Material) 120 mg of astaxanthin raw material was weighed out. 10 mg of dextrin raw material was weighed out. These were mixed well on a spoon using a spatula to obtain Sample 10 (130 mg). The content of astaxanthin-based compounds in Sample 10 was 4.6 wt% in terms of astaxanthin, and the content of dextrin was 7.7 wt%. The ratio of the weight of the astaxanthin-based compounds (astaxanthin equivalent) to the weight of the dextrin in Sample 10 (ataxanthin / dextrin) was 0.6.

[0070] The obtained samples 9 and 10 were subjected to the above coloration evaluation in the same manner as in Example 1. The obtained results are shown in Table 5 below.

[0071]

[0072] As shown in Table 5, for all panelists, the oral discoloration caused by the astaxanthin-class compound of Comparative Example 6, which contained a dextrin raw material, was more difficult to remove than the oral discoloration caused by the astaxanthin-class compound of Comparative Example 5. The "staining inhibition rate by dextrin" in Table 5 above is the value calculated for each panelist by dividing the "total number of gargles in Comparative Example 6 / total number of gargles in Comparative Example 5" and the "total score for Comparative Example 6 / total score for Comparative Example 5." Both values ​​were greater than 1, confirming that oral discoloration caused by the astaxanthin-class compound was difficult to remove for Comparative Example 6, which contained a dextrin raw material, and that oral discoloration caused by the astaxanthin-class compound could not be inhibited by simply using a powdered dextrin raw material.

[0073] Comparative Example 7 (Sample 11: Astaxanthin Raw Material Only) 120 mg of the astaxanthin raw material was weighed out and used as Sample 11.

[0074] Comparative Example 8 (Sample 12: Astaxanthin raw material and cellulose raw material) 120 mg of astaxanthin raw material was weighed out. 10 mg of cellulose raw material was weighed out. These were thoroughly mixed on a spoon using a spatula to obtain Sample 12 (130 mg). The content of astaxanthin-related compounds in Sample 12 was 4.6 wt% in terms of astaxanthin, and the content of cellulose was 7.7 wt%. The ratio of the weight of the astaxanthin-related compounds (astaxanthin equivalent) to the weight of cellulose in Sample 12 (astaxanthin / cellulose) was 0.6.

[0075] The obtained samples 11 and 12 were subjected to the above coloration evaluation in the same manner as in Example 1. The obtained results are shown in Table 6 below.

[0076]

[0077] As shown in Table 6, for all panelists, oral discoloration caused by the astaxanthin-class compound of Comparative Example 8, which contained a cellulose raw material, was more difficult to remove than oral discoloration caused by the astaxanthin-class compound of Comparative Example 7. The "cellulose discoloration suppression rate" in Table 6 above is the value calculated for each panelist by dividing the "total number of gargles in Comparative Example 8 / total number of gargles in Comparative Example 7" and the "total score for Comparative Example 8 / total score for Comparative Example 7." Both values ​​were greater than 1, confirming that oral discoloration caused by the astaxanthin-class compound of Comparative Example 8, which contained a cellulose raw material, was difficult to remove and that the use of a powdered cellulose raw material alone was not sufficient to suppress oral discoloration caused by the astaxanthin-class compound.

[0078] A production example of the oral composition of the present invention is shown below. (Production Example 1) Tablets 100 g of powder containing 2% astaxanthin (astaxanthin 2 g), L-ergothioneine 3 g, vitamin E 50 g, starch 129 g, sucrose fatty acid ester 9 g, silicon oxide 9 g These ingredients were mixed and compressed into tablets with a single-punch tablet press to produce tablets with a diameter of 9 mm and a mass of 300 mg.

[0079] (Formulation Example 2) Capsules Gelatin 60%, Glycerin 30%, Methyl parahydroxybenzoate 0.15%, Propyl parahydroxybenzoate 0.51%, Water (as needed) The following composition was filled into a soft capsule shell made of the above ingredients in a conventional manner to obtain soft capsules weighing 360 mg each: Oil containing 5% astaxanthin 120 mg (astaxanthin 6 mg), L-ergothioneine 10 mg, Glycerin fatty acid ester 15.0 mg, Beeswax 15.0 mg, Wheat germ oil 245 mg

Claims

1. An oral composition comprising an astaxanthin compound and ergothioneine or a salt thereof.

2. The oral composition according to claim 1, wherein the ratio of the weight of the astaxanthin compound in terms of astaxanthin to the weight of ergothioneine or a salt thereof in terms of ergothioneine (weight of the astaxanthin compound in terms of astaxanthin / weight of ergothioneine or a salt thereof in terms of ergothioneine) is 15 or less.

3. The oral composition according to claim 1 or 2, wherein oral coloring caused by the astaxanthin compound is suppressed.

4. The oral composition according to claim 1 or 2, wherein the astaxanthin compound is at least one compound selected from the group consisting of astaxanthin and its derivatives.

5. The oral composition according to claim 1 or 2, wherein the content of the astaxanthin compound is 0.03% by weight or more in terms of astaxanthin.

6. The oral composition according to claim 1 or 2, wherein the oral composition is a capsule, tablet, coated tablet, fine granule, granule, powder, pill, dry syrup, chewable agent, jelly or gummy.

7. An oral coloring inhibitor for an astaxanthin compound, comprising ergothioneine or a salt thereof.

8. Use of ergothioneine or a salt thereof for suppressing oral coloring caused by an astaxanthin compound.

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