Oral compositions

Abstract

The purpose of this invention is to provide an oral composition containing astaxanthin compounds that inhibits oral staining caused by astaxanthin compounds. This invention relates to an oral composition containing astaxanthin compounds and ergothioneine or a salt thereof.

Description

Technical Field

[0001] This invention relates to an oral composition. Furthermore, this invention also relates to an inhibitor of oral staining caused by astaxanthin compounds, and its application in inhibiting oral staining caused by astaxanthin compounds. Background Technology

[0002] Astaxanthin is a red carotenoid widely distributed in the shells and eggs of crustaceans, salmon flesh, and the skin of red snapper, contributing to flesh and body color. Besides its use as a red pigment (Patent Document 1), astaxanthin is also being explored as a pharmaceutical active ingredient due to its strong antioxidant properties (Patent Document 2). Furthermore, in addition to its antioxidant effects, astaxanthin has been found to possess various other beneficial functions (e.g., Patent Document 3). Therefore, astaxanthin holds promise as an effective ingredient in pharmaceuticals or functional foods.

[0003] Patent documents Patent Document 1: Japanese Patent Application Publication No. 2023-119768 Patent Document 2: Japanese Patent No. 3163127 Patent Document 3: Japanese Patent Application Publication No. 9-124470 Patent Document 4: Japanese Patent Application Publication No. 2017-218431 Summary of the Invention

[0004] However, when the inventors were studying oral compositions containing astaxanthin compounds, they discovered that if the composition was held in the mouth, it would cause the oral cavity to turn red due to the astaxanthin compounds.

[0005] The purpose of this invention is to provide an oral composition containing astaxanthin compounds that inhibits oral staining caused by astaxanthin compounds.

[0006] Therefore, the inventors conducted in-depth research to solve the above-mentioned problems and found that when the oral composition containing astaxanthin compounds contains ergothioneine or its salt, the staining in the oral cavity caused by astaxanthin compounds when the composition is held in the mouth is suppressed, thus solving the problem.

[0007] Ergothioneine is an amino acid found in mushrooms and other fungi, naturally occurring in its L-form. L-Ergothioneine is known to have physiological effects such as antioxidant activity. Furthermore, regarding the physiological effects of ergothioneine, for example, Patent Document 4 reports its ability to promote the production of cytokines that activate immune responses. However, there have been no reports on the inhibitory effect of ergothioneine on oral staining; the inventors of this invention are the first to discover that ergothioneine can inhibit oral staining caused by astaxanthin compounds.

[0008] This invention relates to the following oral compositions, etc. [1] An oral composition characterized in that it contains astaxanthin compounds and ergothioneine or its salts. [2] The oral composition according to [1] above is characterized in that the ratio of the weight of the astaxanthin compound to the weight of ergothioneine or its salts converted to ergothioneine is astaxanthin / weight of ergothioneine or its salts converted to ergothioneine is 15 or less. [3] The oral composition according to [1] or [2] above is characterized in that oral staining caused by astaxanthin compounds is inhibited. [4] The oral composition according to any one of [1] to [3] above is characterized in that the astaxanthin compound is a compound selected from at least one of astaxanthin and its derivatives. [5] The oral composition according to any one of [1] to [4] above is characterized in that the content of astaxanthin compounds is 0.03% by weight or more when converted to astaxanthin. [6] The oral composition according to any one of [1] to [5] above is characterized in that the oral composition is a capsule, tablet, coated tablet, granule, pellet, powder, pill, dry syrup, chewable, gel or gummy. [7] An inhibitor of oral staining caused by astaxanthin compounds, characterized in that it contains ergothioneine or a salt thereof. [8] An application characterized in that ergothioneine or its salt is used to inhibit oral staining caused by astaxanthin compounds.

[0009] According to the present invention, an oral composition containing astaxanthin compounds can be provided, wherein oral staining caused by astaxanthin compounds is inhibited. The oral composition containing astaxanthin compounds of the present invention, when taken orally, such as by holding a tablet containing astaxanthin compounds in the mouth or drinking it as a beverage, inhibits the staining in the oral cavity caused by astaxanthin compounds, so it does not cause the user to worry about appearance and can be taken with peace of mind. Detailed Implementation

[0010] The oral composition of the present invention contains astaxanthin compounds and ergothioneine or its salts. In this invention, "oral composition" refers to an oral composition that can be ingested orally and an oral composition suitable for use in the oral cavity. Examples of oral compositions include oral cleaning compositions for oral care, and oral cleaning compositions that are spat out after oral cleaning are also a form of oral composition of this invention. Preferably, the oral composition of this invention is an oral composition that can be ingested orally. The oral composition of the present invention is a composition that inhibits oral staining caused by astaxanthin compounds. The oral composition of the present invention, by containing ergothioneine or its salt, inhibits oral staining caused by astaxanthin compounds compared to compositions without it. Oral staining caused by astaxanthin compounds refers to the red staining phenomenon in the oral cavity caused by astaxanthin compounds upon contact with the tongue or other parts of the mouth. The oral composition of the present invention is preferably a composition that inhibits tongue staining caused by astaxanthin compounds. Furthermore, although the mechanism by which the oral composition of the present invention can inhibit oral staining caused by astaxanthin compounds due to the presence of ergothioneine or its salt is not yet clear, the same effect cannot be obtained even when other powdered substances are added to astaxanthin compounds, and it is therefore considered to be a unique effect of ergothioneine or its salt.

[0011] (Astaxanthin compounds) In this invention, the term "astaxanthin-like compounds" is a general term encompassing compounds including astaxanthin and its derivatives. An astaxanthin-like compound may consist of one or more compounds. Astaxanthin (3,3'-dihydroxy-β,β-carotene-4,4'-dione) is a type of carotenoid. It is a red pigment found in crustaceans such as shrimp and crab, fish such as salmon and sea bream, algae such as green algae and red pharmacodactylus, and yeasts such as red phaf yeast. Astaxanthin exists in three isomers due to the stereoconfiguration of the hydroxyl groups at the 3 (3') positions of the ring structure at both ends of the molecule: 3S, 3'S; 3S, 3'R (meta-iso); and 3R, 3'R. In addition, there are cis and trans geometric isomers with conjugated double bonds in the center of the molecule. Specific examples of geometric isomers include the all-trans, 9-cis, and 13-cis isomers. Astaxanthin can be any one of these compounds, or two or more of them.

[0012] There are no particular restrictions on derivatives of astaxanthin; any compound that has substituents attached to the functional groups of astaxanthin is acceptable, such as esters. The hydroxyl group at the 3 (3') position of astaxanthin can form esters with fatty acids. Astaxanthin esters include monoesters and diesters. Astaxanthin is produced by hydrolyzing the esterified form of astaxanthin. There are no particular restrictions on the fatty acid used to form the above-mentioned esters, but the number of carbon atoms in the fatty acid is preferably 1 to 30. In this invention, astaxanthin, astaxanthin esters, or combinations thereof are preferred as astaxanthin compounds.

[0013] The astaxanthin compounds used in this invention are not limited by their form or manufacturing method. Natural or synthetic astaxanthin compounds can be used. Examples of naturally occurring astaxanthin compounds include algae such as *Haemaphysalis*; yeasts such as *Phaefflera*; crustaceans such as shrimp, krill, and crab; cephalopods such as squid and octopus; various fish and shellfish; plants such as *Calendula officinalis*; bacteria such as *Paracococcus* N81106, *Bacillus* SD212, and *Rhodotorula* PC6; actinomycetes such as *Goldenella* KANMONKAZ-1129; myxobacteria such as *Schizochytrium* KH105; fungi such as *Blancium trispora*; and astaxanthin-producing recombinant organisms, as well as microorganisms, plants, fish, and shellfish. In this invention, for example, an extract containing astaxanthin compounds obtained from the aforementioned microorganisms, plants, fish, and shellfish using known methods can be used to contain the astaxanthin compounds in an oral composition. Furthermore, an astaxanthin compound appropriately purified from the aforementioned extracts containing astaxanthin compounds can be contained in the oral composition. The astaxanthin compounds are preferably astaxanthin compounds extracted from microalgae such as Haematococcus pluvialis, or astaxanthin compounds extracted from fungi such as Bacillus trispora, and more preferably astaxanthin compounds extracted from Haematococcus pluvialis extract. In addition, examples of synthetic astaxanthin compounds include AstaSana (DSM) and Lucantin Pink (registered trademark) (BASF). In addition, synthetic astaxanthin compounds, which are obtained by chemically converting other carotenoids from nature, can be exemplified by AstaMarine (PIVEG Corporation).

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

[0015] There are no particular limitations on the above-mentioned methods for culturing Haematococcus pluvialis, but closed cultivation methods with minimal contamination and reproduction of foreign microorganisms and other impurities are preferred. Examples of such cultivation methods include the use of partially open dome-shaped, conical, or cylindrical cultivation devices and culture media with gas expulsion devices that can move within the devices (International Publication No. 1999 / 050384), methods of applying drying stress to Haematococcus pluvialis to induce algal cyst formation and extracting astaxanthin from the algal culture with cysts (Japanese Patent Application Publication No. 8-103288), methods of placing a light source in a closed cultivation device and irradiating light from the inside, and methods of using plate-shaped culture tanks or tubular culture layers.

[0016] Furthermore, the astaxanthin compounds that can be used in this invention can be extracted from the aforementioned *Haemaphysalis* by breaking the cell walls according to the methods disclosed in Japanese Patent Application Publication No. 5-068585, etc., by adding organic solvents such as acetone, ether, chloroform, and alcohols (ethanol, methanol, etc.), or extraction solvents such as supercritical carbon dioxide. The resulting extract containing astaxanthin compounds, or the substance obtained by appropriately purifying the extract containing astaxanthin compounds as needed, can be included in the composition. The content of astaxanthin compounds in the extract containing astaxanthin compounds is preferably 3-40% by weight, more preferably 3-12% by weight, and even more preferably 5-10% by weight.

[0017] In this invention, commercially available products may be used as astaxanthin compounds or extracts containing them. Examples of commercially available products include AstaReal Oil 200SS (a fat-soluble extract from Haematococcus pluvialis, containing approximately 20% astaxanthin compounds in free form), AstaReal L10, AstaReal Oil 50F, AstaReal Oil 50FC, AstaReal Oil 5F, AstaReal P2AF, AstaTROL-X, AstaReal Powder 20F, water-soluble AstaReal liquid, AstaReal WS liquid, AstaReal 10WS liquid, AstaReal ACT, and AstaVita. e. AstaVitaSports, AstaMate, etc. (all registered trademarks; manufactured by AstaReal and Fuji Chemical Industries, Ltd.); ASTAOTS-S, ASTAOTS-10O, ASTAOTS-ECS, ASTAPTS-2.0PW, ASTAOTS-3.0MB, etc. (ASTOTS are all registered trademarks; manufactured by Fujifilm and Hikari Pure Chemical Industries, Ltd.); BioAstin (registered trademark; manufactured by Cyanotech Corporation); Astazine™ (manufactured by BGG Japan); Astaxanthin powder 1.5%, Astaxanthin powder 2.5%, Astaxanthin oil 5%, Astaxanthin oil 10% (manufactured by BioActives Japan); Astaxanthin (manufactured by Oryza Oil & Fat Chemical); SunActive AX (registered trademark; manufactured by Taiyo Chemical Co., Ltd.); Haematococcus WS30 (manufactured by Yaegaki Fermentation Technology Co., Ltd.); AstaMarine (manufactured by PIVEG Corporation), etc.

[0018] (ergothioneine or its salts) Ergothione is a sulfur-containing amino acid. Salts of ergothioneine can be any pharmacologically permissible or food-grade salt, without particular limitation, and can be either acidic or basic. Examples of acidic 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 and potassium salts; and alkaline earth metal salts such as calcium and magnesium salts.

[0019] Ergothioneine or its salts are not limited by their form or method of manufacture. Ergothioneine or its salts can be chemically synthesized or extracted and purified from natural sources. Ergothioneine is abundant in the Golden / Yellow Oyster mushroom (Pleurotus cornucopiae var. citrinopileatus), a mushroom belonging to the genus Pleurotus in the family Pleurotaceae. Ergothioneine is also found in mushrooms such as white mushrooms, brown mushrooms, and Portabella mushrooms (Agaricus bisporus); oyster mushrooms (Pleurotus ostreatus); shiitake mushrooms (Lentinula edodes); maitake mushrooms (Grifola frondosa); Ganoderma lucidum; Hericium erinaceus; Agrocybe aegerita; chanterelle mushrooms (Cantharellus cibarius); Boletus edulis; and morels (Morchella esculenta). When obtaining ergothioneine from natural sources, extraction from Pleurotus ostreatus is preferred. Ergothioneine or its salts can also be produced through microbial fermentation. Ergothioneine or its salts can also be isolated. Ergothioneine naturally exists in large quantities of L-forms; therefore, the ergothioneine or its salt used in the oral compositions of the present invention is preferably L-ergothioneine or its salt.

[0020] Ergothioneine or its salts are found in natural substances and food products and are compounds with proven edibility. Therefore, from a safety point of view, ergothioneine or its salts are generally considered to pose few problems even with long-term consumption.

[0021] In the oral composition of the present invention, the weight ratio of the astaxanthin-based compound to the weight of ergothioneine or its salts (weight of astaxanthin-based compound / weight of ergothioneine or its salts) is preferably 15 or less. This is because when the above-mentioned weight ratio (weight of astaxanthin-based compound / weight of ergothioneine or its salts) in the oral composition is 15 or less, oral staining caused by astaxanthin compounds can be effectively suppressed. The weight ratio (weight of astaxanthin in the astaxanthin compound / weight of ergothioneine or its salt in the ergothioneine) in the oral composition is more preferably 10 or less, further preferably 6 or less, particularly preferably 4 or less, and most particularly preferably 3.75 or less. The weight ratio (weight of astaxanthin-based astaxanthin compounds / weight of ergothioneine or its salts) 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 embodiment, the weight ratio (weight of astaxanthin-based astaxanthin compounds / weight of ergothioneine or its salts) 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. Regarding the weight of the astaxanthin compounds, when two or more astaxanthin compounds are used, it is their total weight. Furthermore, regarding the weight of ergothioneine or its salts, when two or more ergothioneine or its salts are used, it is their total weight.

[0022] In this specification, the term "astaxanthin conversion" refers to the conversion of astaxanthin values ​​when the astaxanthin compound is not astaxanthin itself. More specifically, the conversion of astaxanthin quantities, or similar expressions, refers to the quantity of astaxanthin when the astaxanthin compound is astaxanthin, and to the value obtained by multiplying the number of moles of the compound by the molecular weight of astaxanthin when the astaxanthin compound is not astaxanthin. The content of astaxanthin compounds in the above composition can be determined by HPLC (high performance liquid chromatography). In addition, when astaxanthin compounds are derivatives of astaxanthin, they can be quantified as astaxanthin through processes such as hydrolysis.

[0023] In this specification, the term "ergothioneine conversion" refers to the conversion of ergothioneine to ergothioneine when ergothioneine is a salt of ergothioneine. More specifically, the conversion of ergothioneine quantity, or similar expressions, refers to the quantity of ergothioneine or its salts when they are ergothioneine, and to the value obtained by multiplying the number of moles of the salt by the molecular weight of ergothioneine when they are salts of ergothioneine. The content of ergothioneine or its salts can be determined by HPLC (High Performance Liquid Chromatography).

[0024] The content of astaxanthin compounds (astaxanthin conversion) contained in the oral composition of the present invention is not particularly limited, and can be set according to their form, etc. The content of astaxanthin compounds in the oral composition of the present invention, for example, when converted to astaxanthin, may be 0.001% by weight or more, preferably more than 0.02% by weight, more preferably 0.03% by weight or more, even more preferably 0.05% by weight or more, and preferably 10% by weight or less, more preferably 5% by weight or less. In one embodiment, the content of astaxanthin compounds, converted to astaxanthin, in the oral composition may be 0.001 to 10% by weight, preferably more than 0.02% by weight and less than 10% by weight, more preferably 0.03 to 10% by weight, and even more preferably 0.05 to 5% by weight. Regarding the content of astaxanthin compounds (astaxanthin conversion) in the oral composition of the present invention, the above-mentioned preferred lower and upper limits can be set as numerical ranges based on an appropriate combination of the composition's morphology.

[0025] The content of ergothioneine or its salt contained in the oral composition of the present invention is not particularly limited and can be set according to its form, etc. The content of ergothioneine or its salt contained in the oral composition of the present invention, converted to ergothioneine, is preferably 0.0001% by weight or more, more preferably 0.001% by weight or more, even more preferably 0.002% by weight or more, particularly preferably 0.003% by weight or more, and further preferably 90% by weight or less, more preferably 50% by weight or less. In one embodiment, the content of ergothioneine or its salt contained in the oral composition of the present invention, converted to ergothioneine, is preferably 0.0001 to 90% by weight, more preferably 0.001 to 50% by weight, even more preferably 0.002 to 50% by weight, and particularly preferably 0.003 to 50% by weight. Regarding the content of ergothioneine or its salts (ergothioneine conversion) in the oral composition of the present invention, the above-mentioned preferred lower and upper limits can be set as numerical ranges according to an appropriate combination of the morphology of the composition.

[0026] The oral composition of the present invention is a composition that inhibits oral staining caused by astaxanthin compounds. Therefore, the oral composition of the present invention does not contain natural foods such as crustaceans' shells and eggs, salmon meat, and the skin of red snapper, which do not cause oral staining caused by astaxanthin compounds.

[0027] The oral compositions of the present invention may be provided in the form of food, medicine, quasi-drug, feed, etc., but are not limited to these. The oral composition of the present invention may contain any additives and ingredients other than the aforementioned astaxanthin compounds and ergothioneine or its salts, provided that the effects of the present invention are not impaired. These additives and ingredients may be selected according to the form of the composition, and may be additives and ingredients commonly used in oral compositions for general food, pharmaceuticals, quasi-drugs, and animal feed. In one embodiment, the oral composition of the present invention may consist of astaxanthin compounds and ergothioneine or its salts.

[0028] The oral composition of the present invention is not particularly limited in form and may be in solid form (powder, granules, tablets, gels, etc.), liquid form, etc., preferably in solid form. 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 capsules (soft capsules, hard capsules), tablets, coated tablets, granules, powders, pills, dry syrups, chewable tablets, gels, or gummies, etc.

[0029] In one embodiment, when the oral composition of the present invention is an oral ingestion composition, the form of the oral ingestion composition is not particularly limited, and it may be in solid form (powder, granules, tablets, gels, etc.), liquid form, etc., preferably in solid form. The oral ingestion composition is preferably a solid oral ingestion composition, for example, it may be in the form of capsules (soft capsules, hard capsules), tablets, coated tablets, granules, powders, pills, dry syrups, chewable tablets, gels, or gummies, etc. Furthermore, in one embodiment, the oral composition of the present invention is an oral composition, which may be in the form of a paste, liquid, chewing gum, etc.

[0030] Astaxanthin compounds are fat-soluble. In one embodiment, from the viewpoint of efficient absorption of astaxanthin compounds, the oral composition of the present invention is preferably dissolved, emulsified, or dispersed in an edible oil. Based on this viewpoint, the oral composition of the present invention also preferably contains an edible oil. As an edible oil, an oil that can dissolve astaxanthin compounds is preferred, such as MCT oil, soybean oil, rapeseed oil, safflower oil, olive oil, palm oil, etc. One or more edible oils may be used.

[0031] The oral composition of the present invention preferably contains at least one selected from emulsifiers, antioxidants, and thickeners. Furthermore, in the present invention, the antioxidants do not contain astaxanthin compounds or ergothioneine or its salts.

[0032] When the oral composition of the present invention contains an antioxidant, it can make the astaxanthin compounds more stable, which is preferred. Examples of antioxidants include vitamin C, vitamin E, BHT, BHA, sodium isoascorbate, propyl gallate, sodium sulfite, potassium sulfite, potassium metabisulfite, sulfur dioxide, etc., and there may be one or more of them.

[0033] When the oral composition of the present invention is formulated into a food or beverage, it can be formulated with astaxanthin compounds and ergothioneine or its salts, as well as other ingredients that can be used in food or beverages (e.g., food materials, additives, etc., as needed) to produce various food or beverages. There are no particular limitations on the type of food or beverage; examples include general food or beverages, health foods, food additives, and their raw materials. There are no particular limitations on the form of the food or beverage; examples include solid, semi-fluid, and fluid forms. When the oral composition of the present invention is a food or beverage, it can be formulated into solid forms such as capsules (soft capsules, hard capsules), tablets, coated tablets, granules, powders, pills, dry syrups, chewable tablets, gels, or gummies, or liquid forms such as oral liquids or syrups; solid forms are preferred. When the oral composition of the present invention is a food or beverage, its form is preferably capsule (soft capsule, hard capsule), tablet, coated tablet, granule, pellet, powder, pill, dry syrup, chewable tablet, gel or gummy.

[0034] When the oral composition of the present invention is formulated into a pharmaceutical or quasi-drug product, astaxanthin compounds, ergothioneine or its salts, and pharmacologically permissible excipients can be added to formulate pharmaceutical products of various dosage forms. The dosage form can be any dosage form for oral administration. Examples of dosage forms for oral pharmaceutical products include, for example, capsules (soft capsules, hard capsules), tablets, coated tablets, granules, powders, pills, dry syrups, chewable tablets, or gummies; gels; and liquid preparations such as oral solutions and syrups. When the oral composition of the present invention is a pharmaceutical or quasi-pharmaceutical product, its form is preferably capsule (soft capsule, hard capsule), tablet, coated tablet, granule, powder, pill, dry syrup, chewable tablet, gel or gummy.

[0035] When the oral composition of the present invention is formulated into feed, it can be formulated with astaxanthin compounds and ergothioneine or its salts, as well as other ingredients that can be used in feed. Examples of feeds include livestock feeds for cattle, pigs, chickens, sheep, horses, etc.; small animal feeds for rabbits, guinea pigs, rats, mice, etc.; and pet food for dogs, cats, birds, etc. When the oral composition of the present invention is used as feed, its form is preferably capsules (soft capsules, hard capsules), tablets, coated tablets, granules, pellets, powders, pills, dry syrups, chewables, gels or gummies.

[0036] When the oral composition of the present invention is a solid composition such as capsules (soft capsules, hard capsules), tablets, coated tablets, granules, powders, pills, dry syrups, chewables, gels, or gummies, the content of astaxanthin compounds (astaxanthin conversion) may be, for example, 0.001% by weight or more, preferably more than 0.02% by weight, more preferably 0.03% by weight or more, and even more preferably 0.05% by weight or more. Furthermore, it is preferably 10% by weight or less, more preferably 5% by weight or less. In one embodiment, when the oral composition is a solid, the content of astaxanthin compounds contained in the composition (astaxanthin conversion) may be 0.001 to 10% by weight, preferably more than 0.02% by weight and less than 10% by weight, more preferably 0.03 to 10% by weight, and even more preferably 0.05 to 5% by weight.

[0037] When the oral composition of the present invention is formulated into food, medicine, quasi-drug, feed, etc., there are no particular limitations on its manufacturing method. Astaxanthin compounds and ergothioneine or their salts can be used to manufacture it by conventional methods. In the manufacture of the oral composition of the present invention, as an astaxanthin compound, ergothioneine or its salt, a purified compound may be used, or raw materials from plants or microorganisms rich in astaxanthin compounds or from plants or microorganisms rich in ergothioneine or its salt may be used.

[0038] In one manner, when a person (adult) ingests or administers the oral composition of the present invention, the total amount of astaxanthin compounds administered, converted to astaxanthin, is preferably 0.5 to 200 mg per day per 60 kg of body weight, more preferably 1 to 100 mg, and even more preferably 3 to 80 mg. In addition, regarding the total dosage of astaxanthin compounds, when there are two or more astaxanthin compounds, it is the total dosage of all of them.

[0039] In one manner, when a person (adult) ingests or administers the oral composition of the present invention, the total dosage of ergothioneine or its salts, converted to ergothioneine, is preferably 0.03 to 100 mg per day per 60 kg of body weight, more preferably 0.07 to 100 mg, and even more preferably 0.2 to 80 mg.

[0040] There is no particular limitation on the subjects (also referred to as subjects) who ingest or administer the oral composition of the present invention, and humans and animals other than humans may be included. The oral composition of the present invention is preferably administered to humans or non-human mammals, more preferably to humans.

[0041] This invention also includes an inhibitor of oral staining caused by astaxanthin compounds containing ergothioneine or its salts. The oral staining inhibitor of this invention is used to inhibit oral staining caused by astaxanthin compounds.

[0042] In addition, the present invention also includes the use of ergothioneine or its salts for inhibiting oral staining caused by astaxanthin compounds.

[0043] In the above-mentioned inhibitors and applications of oral staining caused by astaxanthin compounds, the preferred methods for using astaxanthin compounds and ergothioneine or its salts are the same as those for the oral compositions of the present invention. For example, by mixing ergothioneine or its salts with astaxanthin compounds or oral compositions containing them, oral staining caused by astaxanthin compounds can be inhibited, for example, when the oral composition is taken orally. The preferred amount of ergothioneine or its salts used is the same as that for the oral compositions of the present invention, and their ratios, contents, etc., are also the same as those for the oral compositions of the present invention. For example, with respect to ergothioneine or its salts, the ratio of the weight of astaxanthin in the astaxanthin compound relative to the weight of ergothioneine in the ergothioneine compound or its salts (weight of astaxanthin in the astaxanthin compound / weight of ergothioneine in the ergothioneine compound or its salts) 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, the numerical range represented by the lower limit and upper limit, i.e., "lower limit ~ upper limit", includes both the lower and upper limits. For example, the range represented by "1 ~ 2" refers to 1 and above and 2 and below, including 1 and 2. In this specification, the upper and lower limits can be set as ranges based on any combination. Example

[0045] The present invention will now be described in more detail with reference to specific embodiments. However, the present invention is not limited to these embodiments.

[0046] The astaxanthin, ergothioneine, dextrin, cellulose, and MCT oil used in the following experiments are as follows. Astaxanthin raw material: oil containing 5% astaxanthin Ergothioneine raw material: powder, L-ergothioneine purity 100% Dextrin raw materials: powder, 100% dextrin Cellulose raw material: powder, 100% cellulose MCT oil: manufactured by Nissin Oriol Co., Ltd. In the following tests, the astaxanthin raw material, i.e., oil containing 5% astaxanthin, was removed from the refrigerator, brought to room temperature, heated to 40-50°C, and then brought back to room temperature before use. The ergothionein raw material used was a powdered raw material brought to room temperature. In addition, astaxanthin raw material is an oil raw material obtained by directly diluting the extract of Haematococcus pluvialis (algae), and it is a raw material with an astaxanthin content (conversion value of astaxanthin) of 5.0% by weight.

[0047] <Evaluation Test of Intraoral Staining Inhibition of Ergothioneine and Astaxanthin> <Comparative Example 1> (Sample 1: Astaxanthin raw material) 10 mg of astaxanthin raw material was weighed to achieve a concentration of astaxanthin compounds of 0.5 mg / g (based on astaxanthin conversion). 990 mg of MCT oil was then added and mixed to obtain sample 1 (1000 mg). The content of astaxanthin compounds in sample 1 was 0.05% by weight (based on astaxanthin conversion).

[0048] <Example 1> (Sample 2: Astaxanthin raw material and ergothioneine raw material) Weigh 10 mg of astaxanthin raw material to achieve an astaxanthin concentration of 0.5 mg / g (based on astaxanthin conversion). Add 990 mg of MCT oil to the mixture and stir. Then weigh 0.83 mg of ergothioneine raw material. Thoroughly mix the above-obtained mixture of astaxanthin raw material and MCT oil (1000 mg) and ergothioneine raw material (0.83 mg) on ​​a spoon to obtain sample 2 (1000.83 mg). The astaxanthin content in sample 2 (based on astaxanthin conversion) is 0.05% by weight, and the ergothioneine content is 0.083% by weight. The weight ratio of astaxanthin compounds (based on astaxanthin conversion) to ergothioneine in sample 2 (astaxanthin / ergothioneine) is 0.6.

[0049] (Evaluation of coloring) The prepared sample was placed on the tongue by a professional reviewer to evaluate the staining of astaxanthin compounds in the oral cavity. During the evaluation, the entire amount of the prepared sample (e.g., 1000 mg for sample 1) was placed on the tongue. Specifically, three professional reviewers place a room-temperature sample (sample 1 or sample 2) in a spoon onto the upper part of the tongue in the patient's mouth. They gently stroke the sample with the back of the spoon to evenly distribute it on the front of the upper tongue. Then, they close their mouths and move their tongues for 10 seconds to ensure the sample is distributed throughout the entire oral cavity. Next, they hold 50 mL of water in their mouths to rinse. During rinsing, they hold the 50 mL of water in their mouths all at once, close their mouths, and repeatedly puff out their cheeks 10 times to rinse the oral cavity, then spit out the water. This process of holding the 50 mL of water and rinsing is counted as one rinsing. After one rinsing, the tongue is observed using a mirror. A score of "0" is given when red staining covers more than 10% of the upper tongue's surface area; a score of "△" is given when the staining area is less than 10%; and a score of "×" is given when no staining is observed. When the score is "0" or "△", the same rinsing process is repeated, followed by mirror observation and evaluation. Repeat the above process of rinsing with 50 mL of water and evaluating the tongue staining until the upper part of the tongue is completely free of red staining (evaluation "×").

[0050] The test results for Sample 1 and Sample 2 are shown in Table 1 below. The staining inhibition effect was evaluated by the total number of rinsing sessions until the tongue staining disappeared and the total score shown in the table. The fewer the total number of rinsing sessions, the more the astaxanthin compounds inhibited tongue staining. The total score in the table is obtained by assigning scores to the observation results of the tongue from the first rinsing session until the staining disappeared, with "0" equaling 2 points, "△" equaling 1 point, and "×" equaling 0 points, and then summing the scores for each professional reviewer. This total score represents the degree of tongue staining; the smaller the total score, the more the astaxanthin compounds inhibited tongue staining. For example, for Sample 1, Professional Reviewer 1's evaluation result after the first rinsing session was "0" (2 points), after the second rinsing session was "△" (1 point), and after the third rinsing session was "×" (0 points). Therefore, professional reviewer 1 evaluated sample 1 by rinsing a total of 3 times, with a total score of 1 "0" (2 points), 1 "△" (1 point), and 1 "×" (0 points), for a total of 3 points. Calculate the average of the total number of rinsing times and the total score of the 3 professional reviewers. In Tables 1 to 4, "Ast / Erg (weight ratio)" represents the weight ratio of astaxanthin compounds (Ast) to the weight of ergothioneine (Erg) in the sample.

[0051] [Table 1]

[0052] As shown in Table 1, in all professional reviews, the oral staining caused by astaxanthin compounds in Sample 2, which contains ergothioneine, was more easily cleared compared to the oral staining caused by astaxanthin compounds in Sample 1. The "Staining Inhibition Rate Based on Erg" in Table 1 refers to the values ​​of "Total Number of Rinsings in Example 1 / Total Number of Rinsings in Comparative Example 1" and "Total Score of Example 1 / Total Score of Comparative Example 1" calculated for each professional reviewer. Since all values ​​are less than 1, this indicates that oral staining caused by astaxanthin compounds was inhibited in Example 1, which contains ergothioneine. Furthermore, the degree of tongue staining caused by astaxanthin compounds varied among the professional reviewers, which is an individual-specific variability. Therefore, the inhibitory effect of astaxanthin compounds on tongue staining was confirmed by calculating the staining inhibition rate of the same professional reviewer (e.g., professional reviewer A) compared to the tongue staining caused by sample 1 in Comparative Example 1 with that caused by sample 2 in Example 1. The following examples were handled in the same manner.

[0053] <Comparative Example 2> (Sample 3: Astaxanthin raw material only) Weigh 120 mg of astaxanthin raw material as sample 3.

[0054] <Example 2> (Sample 4: Astaxanthin raw material and ergothioneine raw material) Weigh 120 mg of astaxanthin raw material. Weigh 10 mg of ergothioneine raw material. Mix the astaxanthin raw material (120 mg) and ergothioneine raw material (10 mg) thoroughly on a spoon using a spatula to obtain sample 4 (130 mg). The content of astaxanthin compounds in sample 4, converted to astaxanthin, is 4.6% by weight, and the content of ergothioneine is 7.7% by weight. The weight ratio of astaxanthin compounds (converted to astaxanthin) in sample 4 relative to the weight of ergothioneine (astaxanthin / ergothioneine) is 0.6.

[0055] For the obtained samples 3 and 4, except for the N=3 experiment, the above color evaluation was performed by 3 professional reviewers using the same method as in Example 1. The results are shown in Table 2 below.

[0056] [Table 2]

[0057] As shown in Table 2, in all professional reviews, the oral staining caused by the astaxanthin compounds in Example 2, which contained ergothioneine, was more easily cleared compared to the oral staining caused by the astaxanthin compounds in Comparative Example 2. The "Staining Inhibition Rate Based on Erg" in Table 2 refers to the values ​​of "Total Number of Rinsings in Example 2 / Total Number of Rinsings in Comparative Example 2" and "Total Score of Example 2 / Total Score of Comparative Example 2" calculated for each professional reviewer. Since all values ​​are much less than 1, this indicates that oral staining caused by astaxanthin compounds was inhibited in Example 2, which contained ergothioneine.

[0058] <Comparative Example 3> (Sample 5: Astaxanthin raw material) Weigh 120 mg of astaxanthin raw material as sample 5.

[0059] <Example 3> (Sample 6: Astaxanthin raw material and ergothioneine raw material) Weigh 120 mg of astaxanthin raw material. Weigh 1.0 mg of ergothioneine raw material. Mix these thoroughly on a spoon with a spatula to obtain sample 6 (121 mg). The content of astaxanthin compounds in sample 6, converted to astaxanthin, is 5.0% by weight, and the content of ergothioneine is 0.83% by weight. The weight ratio of astaxanthin compounds (converted to astaxanthin) to ergothioneine in sample 6 (astaxanthin / ergothioneine) is 6.

[0060] For the obtained samples 5 and 6, the above colorimetric evaluation was performed using the same method as in Example 1. The results are shown in Table 3 below.

[0061] [Table 3]

[0062] As shown in Table 3, in all professional reviews, the oral staining caused by the astaxanthin compounds in Example 3, which contained ergothioneine, was more easily cleared compared to the oral staining caused by the astaxanthin compounds in Comparative Example 3. The "Staining Inhibition Rate Based on Erg" in Table 3 refers to the values ​​of "Total Number of Rinsings in Example 3 / Total Number of Rinsings in Comparative Example 3" and "Total Score of Example 3 / Total Score of Comparative Example 3" calculated for each professional reviewer. Since all values ​​are much less than 1, this indicates that the oral staining caused by the astaxanthin compounds was sufficiently inhibited in Example 3, which contained ergothioneine. Furthermore, in Tables 2 and 3 above, the amount and concentration of astaxanthin raw material in Sample 3 of Comparative Example 2 and Sample 5 of Comparative Example 3 were the same, but the total number of rinsing attempts and total scores of each professional reviewer differed. This was due to the different test dates and time periods, which caused changes in the tongue condition of each professional reviewer. Therefore, in this test, the confirmation of the inhibitory effect of astaxanthin compounds on tongue staining was carried out by comparing tests conducted on the same day and time period for the same professional reviewer. Other tests were conducted in the same manner.

[0063] <Comparative Example 4> (Sample 7: Astaxanthin raw material) Weigh 300 mg of astaxanthin raw material as sample 7.

[0064] <Example 4> (Sample 8: Astaxanthin raw material and ergothioneine raw material) Weigh 300 mg of astaxanthin raw material. Weigh 1.0 mg of ergothioneine raw material. Mix these thoroughly on a spoon using a spatula to obtain sample 8 (400 mg). The content of astaxanthin compounds in sample 8, converted to astaxanthin, is 5.0% by weight, and the content of ergothioneine is 0.33% by weight. The weight ratio (astaxanthin / ergothioneine) of astaxanthin compounds relative to the weight of ergothioneine in sample 8 is 15.

[0065] For the obtained samples 7 and 8, the above colorimetric evaluation was performed using the same method as in Example 1. The results are shown in Table 4 below.

[0066] [Table 4]

[0067] As shown in Table 4, in all professional reviews, the oral staining caused by the astaxanthin compounds in Example 4, which contained ergothioneine, was more easily cleared compared to the oral staining caused by the astaxanthin compounds in Comparative Example 4. The "Staining Inhibition Rate Based on Erg" in Table 4 refers to the values ​​of "Total Number of Rinsings in Example 4 / Total Number of Rinsings in Comparative Example 4" and "Total Score of Example 4 / Total Score of Comparative Example 4" calculated for each professional reviewer. Since all values ​​are less than 1, this indicates that oral staining caused by astaxanthin compounds was inhibited in Example 4, which contained ergothioneine.

[0068] <Comparative Example 5> (Sample 9: Astaxanthin raw material only) Weigh 120 mg of astaxanthin raw material as sample 9.

[0069] <Comparative Example 6> (Sample 10: Astaxanthin raw material and dextrin raw material) Weigh 120 mg of astaxanthin raw material. Weigh 10 mg of dextrin raw material. Mix these thoroughly on a spoon using a spatula to obtain sample 10 (130 mg). The content of astaxanthin compounds in sample 10, converted to astaxanthin, is 4.6% by weight, and the content of dextrin is 7.7% by weight. The weight ratio of astaxanthin compounds (converted to astaxanthin) in sample 10 relative to the weight of dextrin (astaxanthin / dextrin) is 0.6.

[0070] For the obtained samples 9 and 10, the above colorimetric evaluation was performed using the same method as in Example 1. The results are shown in Table 5 below.

[0071] [Table 5]

[0072] As shown in Table 5, in all professional reviewers, the oral staining caused by astaxanthin compounds in Comparative Example 6, which contains dextrin, was more difficult to remove than the oral staining caused by astaxanthin compounds in Comparative Example 5. The "staining inhibition rate based on dextrin" in Table 5 refers to the values ​​of "total number of rinses in Comparative Example 6 / total number of rinses in Comparative Example 5" and "total score of Comparative Example 6 / total score of Comparative Example 5" calculated for each professional reviewer. Since all values ​​are greater than 1, it is confirmed that the oral staining caused by astaxanthin compounds in Comparative Example 6, which contains dextrin, is difficult to remove, and the oral staining caused by astaxanthin compounds cannot be inhibited when only powdered dextrin is used.

[0073] <Comparative Example 7> (Sample 11: Astaxanthin raw material only) Weigh 120 mg of astaxanthin raw material as sample 11.

[0074] <Comparative Example 8> (Sample 12: Astaxanthin raw material and cellulose raw material) Weigh 120 mg of astaxanthin raw material. Weigh 10 mg of cellulose raw material. Mix these thoroughly on a spoon using a spatula to obtain sample 12 (130 mg). The content of astaxanthin compounds in sample 12, converted to astaxanthin, is 4.6% by weight, and the content of cellulose is 7.7% by weight. The ratio of the weight of astaxanthin compounds (converted to astaxanthin) to the weight of cellulose in sample 12 (astaxanthin / cellulose) is 0.6.

[0075] For the obtained samples 11 and 12, the above color evaluation was performed using the same method as in Example 1. The results are shown in Table 6 below.

[0076] [Table 6]

[0077] As shown in Table 6, in all professional reviewers, the oral staining caused by astaxanthin compounds in Comparative Example 8, which contains cellulose raw material, was more difficult to remove than the oral staining caused by astaxanthin compounds in Comparative Example 7. The "staining inhibition rate based on cellulose" in Table 6 refers to the values ​​of "total number of rinses in Comparative Example 8 / total number of rinses in Comparative Example 7" and "total score of Comparative Example 8 / total score of Comparative Example 7" calculated for each professional reviewer. Since all values ​​are greater than 1, it is confirmed that the oral staining caused by astaxanthin compounds in Comparative Example 8, which contains cellulose raw material, is difficult to remove, and the oral staining caused by astaxanthin compounds cannot be inhibited when only powdered cellulose raw material is used.

[0078] Examples of the manufacture of the oral compositions of the present invention are shown below. (Manufacturing Example 1) Tablets 100g of powder containing 2% astaxanthin (2g astaxanthin) L-ergothioneine 3g Vitamin E 50g 129g of starch 9g of sucrose fatty acid ester 9g of silicon dioxide These are mixed and compressed using a single-shot tableting machine to produce tablets with a diameter of 9 mm and a mass of 300 mg.

[0079] (Formulation Example 2) Capsules 60% gelatin 30% glycerin Methylparaben 0.15% 0.51% propylparaben Water appropriate amount The soft capsule shell, composed of the above ingredients, is filled with the following composition using conventional methods to obtain soft capsules of 360 mg each: 120mg of oil containing 5% astaxanthin (6mg astaxanthin) L-ergothioneine 10mg Glyceryl fatty acid esters 15.0 mg Beeswax 15.0mg Wheat germ oil 245mg.

Claims

1. An oral composition, characterized in that, It contains astaxanthin compounds and ergothioneine or its salts.

2. The oral composition according to claim 1, characterized in that, The ratio of the weight of astaxanthin in an astaxanthin compound to the weight of ergothioneine or its salts, i.e., the weight of astaxanthin in an astaxanthin compound / the weight of ergothioneine or its salts, is less than 15.

3. The oral composition according to claim 1 or 2, characterized in that, Oral staining caused by astaxanthin compounds was inhibited.

4. The oral composition according to claim 1 or 2, characterized in that, Astaxanthin compounds are compounds selected from at least one of astaxanthin and its derivatives.

5. The oral composition according to claim 1 or 2, characterized in that, The content of astaxanthin compounds, converted to astaxanthin, is 0.03% by weight or more.

6. The oral composition according to claim 1 or 2, characterized in that, The oral composition is in the form of capsules, tablets, coated tablets, granules, pellets, powders, pills, dry syrups, chewable tablets, gels, or gummies.

7. An inhibitor of oral staining caused by astaxanthin compounds, characterized in that, It contains ergothioneine or its salts.

8. An application characterized in that, Ergothioneine or its salts are used to inhibit oral staining caused by astaxanthin compounds.

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