Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P9/00—Drugs for disorders of the cardiovascular system
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
  • C07C46/00—Preparation of quinones
  • C07C46/10—Separation; Purification; Stabilisation; Use of additives
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P17/00—Drugs for dermatological disorders
  • A61P17/18—Antioxidants, e.g. antiradicals
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P39/00—General protective or antinoxious agents
  • A61P39/06—Free radical scavengers or antioxidants
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Definitions

• One or more embodiments of the present invention relate to a method for preserving reduced coenzyme Q10, a method for inhibiting oxidation of reduced coenzyme Q10, and a composition containing reduced coenzyme Q10.
• Coenzyme Q is an essential component that is widely distributed in living organisms, from bacteria to mammals, and is known as a component of the mitochondrial electron transport system in cells in living organisms.
• coenzyme Q10 which has 10 repeating structures in the side chain of coenzyme Q, is the main component, and about 40 to 90% of the coenzyme exists in vivo as a reduced form.
• Physiological actions of coenzyme Q include activation of energy production by mitochondrial activation, activation of cardiac function, stabilization of cell membranes, and protection of cells by antioxidant action.
• QH reduced coenzyme Q10
• Patent Document 1 A general method for obtaining reduced coenzyme Q10 has already been disclosed (Patent Document 1).
• Patent Document 2 describes that crystal polymorphism is observed in reduced coenzyme Q10. or "QH Form II type crystal" is much more stable than conventional reduced coenzyme Q10 (hereinafter, this crystal is referred to as "Form I type crystal of reduced coenzyme Q10" or "QH Form I type crystal"), Other physical properties are also reported to be excellent.
• Patent Documents 3, 4, and 5, for example, are examples of documents that disclose techniques for suppressing the oxidation of reduced coenzyme Q10 and stably preserving it.
• reduced coenzyme Q10 having high oxidation stability and high bioabsorbability
• a particulate composition in which an oily component containing reduced coenzyme Q10 or an oily component containing reduced coenzyme Q10 and a lipophilic antioxidant forms domains and is polydispersed is described, and the particles
• a method for stabilizing a particulate composition is described, which comprises exposing the particulate composition to an ambient relative humidity of 90% or less.
• water-soluble excipients include gum arabic and gelatin.
• Patent Documents 3 to 5 are all techniques for improving oxidation stability by covering QH with a film of gas barrier material such as gum arabic and gelatin.
• Non-Patent Documents 1 and 2 It is known that the stability of organic compounds generally decreases as the relative humidity increases.
• Patent Document 6 describes that a co-crystal containing reduced coenzyme Q10 and a compound such as 3,4-dihydroxybenzoic acid was found as a further form of reduced coenzyme Q10.
• Patent Document 7 describes that reduced coenzyme Q10 and nicotinamide form a co-crystal. Co-crystallization of reduced coenzyme Q10 and one or more other compounds may improve the oxidation stability of reduced coenzyme Q10. Can not.
• Patent Documents 3 to 5 disclose QH products that prevent oxidation of reduced coenzyme Q10 (QH) and can be stored stably. However, in Patent Documents 3 to 5, the applications of QH are limited because they all require formulation of QH with specific ingredients.
• one or more embodiments of the present invention provide methods of preserving QH that can inhibit oxidation of QH without requiring formulation of QH, methods of inhibiting oxidation of QH, and compositions comprising QH. offer.
• a method for storing reduced coenzyme Q10 comprising: A method comprising storing a composition containing reduced coenzyme Q10 and having a water activity of 0.50 or more at 25°C. (2) the composition is a mixed composition in which the reduced coenzyme Q10 and one or more other components are mixed; (1) The method as described in. (3) The composition is a multiphase composition comprising a first phase containing the reduced coenzyme Q10 and a second phase containing one or more other components, which are placed in contact with each other. , (1) The method as described in.
• the reduced coenzyme Q10 is a Form I crystal of reduced coenzyme Q10, a Form II crystal of reduced coenzyme Q10, a co-crystal consisting of reduced coenzyme Q10 and one or more other compounds, or a reduced coenzyme. Any one of (1) to (3), which is one or more selected from an amorphous solid of enzyme Q10 and a composition in which reduced coenzyme Q10 is dissolved in a solvent and/or a fat-soluble medium described method. (5) the composition comprises a substance that releases water; (1) The method according to any one of (4).
• a method for suppressing oxidation of reduced coenzyme Q10 comprising: A method comprising storing a composition containing reduced coenzyme Q10 and having a water activity of 0.50 or more at 25°C. (7) the composition is a mixed composition in which the reduced coenzyme Q10 and one or more other components are mixed; (6) The method according to. (8) The composition is a multi-phase composition comprising a first phase containing the reduced coenzyme Q10 and a second phase containing one or more other components, which are placed in contact with each other. , (6) The method according to.
• the reduced coenzyme Q10 is a Form I crystal of reduced coenzyme Q10, a Form II crystal of reduced coenzyme Q10, a co-crystal consisting of reduced coenzyme Q10 and one or more other compounds, or a reduced coenzyme.
• the composition comprises a substance that releases water; (6) The method according to any one of (9).
• (11) A composition comprising reduced coenzyme Q10 and having a water activity of 0.50 or more at 25°C.
• QH reduced coenzyme Q10 (QH) disclosed in the present specification
• QH can be stably stored while preventing oxidation.
• oxidation of QH can be effectively prevented.
• composition containing QH disclosed in the present specification oxidation of QH can be prevented and stored stably.
• “reduced coenzyme Q10” may partially contain oxidized coenzyme Q10 as long as it contains reduced coenzyme Q10 as a main component.
• the main component is, for example, 50% by weight or more, usually 60% by weight or more, preferably 70% by weight or more, more preferably 80% by weight or more, still more preferably 90% by weight or more, particularly preferably 95% by weight. Above, it means that the content is more than 98% by weight.
• the ratio is the ratio of reduced coenzyme Q10 to the total amount of coenzyme Q10.
• reduced coenzyme Q10 has two crystal polymorphs, Form I and Form II. Specifically, the melting point is around 48° C., and the diffraction angles (2 ⁇ 0.2°) are 3.1°, 18.7°, 19.0°, and 20° in powder X-ray (Cu—K ⁇ ) diffraction.
• the crystal form of reduced coenzyme Q10 showing characteristic peaks at .2° and 23.0° is Form I type crystal, and has a melting point of around 52°C.
• Reduced coenzyme Q10 showing characteristic peaks at angles (2 ⁇ 0.2°) of 11.5°, 18.2°, 19.3°, 22.3°, 23.0° and 33.3° is a Form II crystal.
• the reduced coenzyme Q10 is a QH Form I type crystal, a QH Form II type crystal, a co-crystal composed of reduced coenzyme Q10 and one or more other compounds, and an amorphous solid of QH. , and a composition in which QH is dissolved in a solvent and/or a fat-soluble medium.
• the solvent is not particularly limited as long as it can dissolve QH. Examples of the solvent include alcohols, hydrocarbons, ketones, terpenes, oils and fats, essential oils, and propylene glycol fatty acid esters.
• the fat-soluble medium is not particularly limited as long as it is a substance capable of dissolving QH.
• the fat-soluble medium examples include fatty acids, emulsifiers, fat-soluble vitamins, vitamin derivatives, and the like.
• Compositions in which QH is dissolved in a solvent and/or in a lipophilic medium are used to carry out methods according to one or more embodiments of the invention or to store or use compositions according to one or more embodiments of the invention. It may be a liquid composition or a solid composition under temperature conditions, but a liquid composition is preferred.
• the one or more other compounds contained in the co-crystal composed of QH and one or more other compounds are not particularly limited as long as they are compounds capable of forming a co-crystal with QH. Examples include benzoic acid and derivatives thereof. organic carboxylic acids, including resorcinol, benzyl alcohol, organic alcohols including phenol and its derivatives, urea, nicotinamide, and the like.
• the other one or more compounds may be one or more, and may be one or two or more, preferably one to three compounds.
• the alcohols are not particularly limited, regardless of whether they are cyclic or non-cyclic, and whether they are saturated or unsaturated. Generally, those having 1 to 20 carbon atoms are mentioned, preferably 1 to 12 carbon atoms, more preferably 1 to 5 carbon atoms, particularly preferably 1 to 4 carbon atoms, and among these, monohydric alcohols are preferred. Most preferably, it is a monohydric alcohol having 2 carbon atoms. Dihydric alcohols having 2 to 5 carbon atoms, preferably 2 to 4 carbon atoms, more preferably 3 carbon atoms, and trihydric alcohols having 3 carbon atoms are also suitably used.
• Monohydric alcohols include, for example, methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, 2-butanol, isobutyl alcohol, tert-butyl alcohol, 1-pentanol, 2-pentanol, 3-pen Tanol, 2-methyl-1-butanol, isopentyl alcohol, tert-pentyl alcohol, 3-methyl-2-butanol, neopentyl alcohol, 1-hexanol, 2-methyl-1-pentanol, 4-methyl-2- Pentanol, 2-ethyl-1-butanol, 1-heptanol, 2-heptanol, 3-heptanol, 1-octanol, 2-octanol, 2-ethyl-1-hexanol, 1-nonanol, 1-decanol, 1-undecanol , 1-dodecanol, allyl alcohol, propargyl alcohol, benzyl
• Dihydric alcohols include 1,2-ethanediol, 1,2-propanediol (propylene glycol), 1,3-propanediol, 1,2-butanediol, 1,3-butanediol, 1,4- Butanediol, 2,3-butanediol, 1,5-pentanediol and the like can be mentioned.
• Preferred are 1,2-ethanediol, 1,2-propanediol, 1,3-butanediol and 1,3-propanediol, and most preferred is 1,2-propanediol.
• glycerin As the trihydric alcohol, glycerin or the like can be suitably used.
• the hydrocarbons are not particularly limited, but may include, for example, aliphatic hydrocarbons, aromatic hydrocarbons, halogenated hydrocarbons, and the like. Aliphatic hydrocarbons and aromatic hydrocarbons are particularly preferred, and aliphatic hydrocarbons are particularly preferred.
• the aliphatic hydrocarbon is not particularly limited regardless of whether it is cyclic or non-cyclic, and whether it is saturated or unsaturated, but non-cyclic aliphatic hydrocarbons are particularly preferably used. Further, those having 3 to 20 carbon atoms, preferably 5 to 12 carbon atoms are usually used.
• cyclohexane 1-hexene, cyclohexene, heptane, 2-methylhexane, 3-methylhexane, 2,3-dimethylpentane, 2,4-dimethylpentane, methylcyclohexane, 1-heptene, octane, 2,2,3- trimethylpentane, isooctane, ethylcyclohexane, 1-octene, nonane, 2,2,5-trimethylhexane, 1-nonene, decane, 1-decene, p-menthane, undecane, dodecane and the like.
• the ketones are not particularly limited regardless of whether they are cyclic or non-cyclic, saturated or unsaturated. Specific examples include acetone, methyl ethyl ketone, methyl butyl ketone, methyl isobutyl ketone, acetophenone, 4-methoxyphenylacetone, paramethylacetophenone, methyl ⁇ -naphthyl ketone and the like, preferably acetone, acetophenone, They are 4-methoxyphenylacetone, paramethylacetophenone, and methyl ethyl ketone.
• the terpenes are not particularly limited, and any of hemiterpene, monoterpene, sesquiterpene, diterpene, sesterterpene, and triterpene can be suitably used. Among them, from the viewpoint of solubility in QH, hemiterpene, monoterpene and sesquiterpene are more preferable, monoterpene and sesquiterpene are particularly preferable, and monoterpene is most preferable.
• terpenes include prenol, 3-methyl-3-buten-2-ol, tiglic acid, angelic acid, senateic acid, isovaleric acid, alloocimene, ⁇ -bourvonene, ⁇ -cadinene, dehydro-p - cymene, menthol, dl-limonene, d-limonene, l-limonene, p-cymene, ⁇ -pinene, valencene, myrcene, bisabolene, carene, caryophyllene, terpinene, phytol, cis-3,7-dimethyl-1,3 , 6-octatriene, ⁇ -elemene, ⁇ -elemene, ⁇ -farnesene, ⁇ -farnesene, farnesene, germacrene D, ⁇ -guayene, longifolene, ⁇ -ocimene, ⁇ -
• the fats and oils may be natural fats and oils from animals and plants, synthetic fats and oils, and processed fats and oils.
• vegetable oils and fats include coconut oil, palm oil, palm kernel oil, linseed oil, camellia oil, brown rice germ oil, rapeseed oil, rice oil, peanut oil, corn oil, wheat germ oil, soybean oil, perilla oil, cottonseed oil, Sunflower seed oil, kapok oil, evening primrose oil, shea butter, monkey fat, cacao butter, sesame oil, safflower oil, olive oil, avocado oil, poppy seed oil, burdock root oil, etc. can be mentioned.
• Lard, milk fat, fish oil, beef tallow, and the like can be mentioned, and fats and oils (for example, hydrogenated oil) obtained by processing these by fractionation, hydrogenation, transesterification, etc. can also be mentioned.
• fats and oils for example, hydrogenated oil
• MCT medium chain triglycerides
• partial glycerides of fatty acids and the like can also be used. A mixture of these may also be used.
• the medium-chain fatty acid triglyceride is not particularly limited, but includes, for example, triglycerides in which each fatty acid has 6 to 12 carbon atoms, preferably 8 to 12 carbon atoms.
• the essential oil is not particularly limited, it is preferably an essential oil containing terpenes, such as orange oil, capsicum oil, mustard oil, garlic oil, caraway oil, clove oil, cinnamon oil, cocoa extract, and coffee bean extract.
• the propylene glycol fatty acid ester is not particularly limited as a propylene glycol fatty acid ester, but propylene glycol monocaprylate, propylene glycol dicaprylate, propylene glycol monocaprate, propylene glycol dicaprate, propylene glycol monolaurate.
• fatty acids examples include caprylic acid, capric acid, lauric acid, myristic acid, palmitic acid, stearic acid, isostearic acid, oleic acid, linoleic acid, and linolenic acid.
• emulsifier examples include glycerin fatty acid esters, sucrose fatty acid esters, sorbitan fatty acid esters, polyglycerin condensed ricinoleic acid esters, polyoxyethylene sorbitan fatty acid esters, saponins, and phospholipids.
• Phospholipids are not particularly limited, but examples include lecithins such as egg yolk lecithin and refined soybean lecithin, phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, sphingomyelin, dicetyl phosphate, stearylamine, phosphatidylglycerol, phosphatidic acid, phosphatidylinositolamine, cardiolipin, ceramide phosphorylethanolamine, ceramide phosphorylglycerol, mixtures thereof, and the like.
• Phospholipids (hydrogenated lecithin and lysolecithin) subjected to processing such as hydrogenation and enzymatic decomposition can also be used.
• fat-soluble vitamins examples include vitamin E, vitamin A, vitamin D, vitamin K, and the like.
• Examples of the derivatives of vitamins include derivatives of fat-soluble vitamins and fat-soluble derivatives of water-soluble vitamins.
• examples of water-soluble vitamins include vitamin C, vitamin B1, vitamin B2, vitamin B6, vitamin B12, niacin, pantothenic acid, folic acid, biotin and the like.
• the QH used in one or more embodiments of the present invention need not be pre-formulated.
• the QH is a non-preformulated QH, such as QH Form I crystals, QH Form II crystals, co-crystals of QH and one or more other compounds, amorphous solids of QH, and , QH is preferably composed of only one or more selected from compositions dissolved in a solvent and/or a fat-soluble medium, because QH can be used in a wide range of applications.
• the QH is a pre-formulated QH (e.g., an inclusion complex of QH with a cyclodextrin, a QH dispersed in a matrix containing a water-soluble excipient in a particulate composition, a coating medium in a solid formulation). not QH coated with (or capsules of QH).
• a pre-formulated QH e.g., an inclusion complex of QH with a cyclodextrin, a QH dispersed in a matrix containing a water-soluble excipient in a particulate composition, a coating medium in a solid formulation.
• the water-soluble excipient can be, for example, one or more selected from the group consisting of water-soluble polymers, surfactants, sugars, and yeast cell walls.
• the coating medium can be, for example, an oil-soluble coating medium or a water-soluble coating medium.
• the oil-soluble coating medium can be, for example, sugar esters of higher fatty acids, shellac, cellulose derivatives, fatty acids and their ester derivatives, oils and fats, zein and the like.
• Examples of the water-soluble coating medium include gelatin, sugar, gum arabic, sugar esters of higher fatty acids, tragacanth, pectin, pullulan, alginic acid, dried egg white, milk, curdlan, cellulose derivatives, casein, casein compounds, starch, and yeast. It can be a cell wall or the like.
• the capsule is, for example, QH encapsulated with a soft capsule, hard capsule, microcapsule, or the like.
• Materials for the capsule include, for example, gelatin derived from bovine bone, bovine skin, pig skin, fish skin, etc.; seaweed-derived products such as carrageenan and alginic acid that can be used as food additives; locust bean gum, guar gum, etc. Products derived from plant seeds; production agents containing celluloses; starches such as wheat starch, potato starch, sweet potato starch, corn starch, and dextrin.
• a first embodiment of the present invention comprises: A method for storing QH, comprising: A method comprising storing a composition comprising QH and having a water activity of 0.50 or higher at 25°C.
• the method according to the present embodiment it is possible to suppress oxidation of QH and stably store QH.
• Common compounds are said to be unstable in the presence of water, and it is important to store them in a dry state.
• QH is stabilized in a state contained in a composition having a water activity of 0.50 or more at 25 ° C., which is contrary to the above-mentioned common theory, and utilizes the characteristic property of QH to stabilize QH. It is possible to keep The preparation of said composition is easy to carry out. Therefore, the method according to this embodiment can be a means for stabilizing QH efficiently at low cost.
• QH Form II crystals, co-crystals consisting of QH and one or more other compounds, and QH in the form of compositions in which QH is dissolved in a solvent and/or in a lipid-soluble medium have high production costs per se, and are therefore difficult to store.
• the subsequent QH residual rate (see Examples for definition) is 90% or more.
• QH when QH is in the form of a QHFormII type crystal, a cocrystal consisting of QH and one or more other compounds, or a composition in which QH is dissolved in a solvent and/or a fat-soluble medium It is preferable because the QH residual rate of QH after storage can be 90% or more.
• QH in the form of QHFormI type crystal can be produced at low cost, but is susceptible to oxidation. of QH at an appropriate price.
• the method according to the present embodiment is preferable because the QH residual rate of QH after storage can be 40% or more when QH is in the form of a QH Form I type crystal.
• composition containing QH and having a water activity of 0.50 or more at 25°C in the method according to the present embodiment will be described below.
• the water activity of the composition can be measured by a conventional method.
• the water activity of the composition at 25° C. is preferably 0.53 or higher, more preferably 0.60 or higher, still more preferably 0.70 or higher, further preferably 0.75 or higher, further preferably 0.80 or higher, 0.85 or more is more preferable, and 0.90 or more is particularly preferable.
• the water activity is preferably 0.53 or more, more preferably 0.60 or more, still more preferably 0.70 or more, further preferably 0.75 or more, and 0.80 0.85 or more is more preferable, and 0.90 or more is particularly preferable.
• QH is not a Form I type crystal
• the water activity is preferably 0.53 or higher, more preferably 0.60 or higher, particularly preferably 0.70 or higher, and most preferably 0.75 or higher.
• the composition may contain one or more other ingredients in addition to QH.
• the one or more other ingredients may be ingredients that are used in combination with QH, and include, for example, ingredients that are acceptable as foods, cosmetics, or pharmaceuticals.
• the composition when at least one of a cocrystal consisting of QH and one or more other compounds, and a composition in which QH is dissolved in a solvent and/or a fat-soluble medium is used as QH, the one or more The other component of refers to the co-crystal and one or more other components contained in the solvent and/or other than the fat-soluble medium.
• the one or more other ingredients are preferably one or more ingredients containing water or a substance that releases water in order to adjust the water activity of the composition to 0.50 or more at 25°C.
• “one or more water-containing ingredients” include water or one or more water-containing ingredients selected from carbohydrates, carbohydrates, proteins, lipids, salts, and the like.
• Water means water that exists as a liquid, and does not have to be pure water, and may exist as an aqueous solution.
• the aqueous solution may be an aqueous salt solution in which an inorganic salt is dissolved in water to adjust the water activity below 1.0.
• a "water-releasing material” is a material that slowly releases water vapor.
• the composition is a mixed composition in which QH and one or more other ingredients are mixed.
• the mixed composition as a whole can be a food, cosmetic or pharmaceutical acceptable composition.
• the mixed composition may be a mixed composition in which QH and one or more other components are uniformly mixed, or a mixed composition in which QH and one or more other components are nonuniformly mixed.
• a homogeneously mixed mixed composition refers to a composition comprising QH and one or more other ingredients, wherein the concentration distribution of QH is uniform or substantially uniform throughout the composition.
• a homogeneously mixed composition can be obtained, for example, by thoroughly mixing QH with one or more other ingredients.
• a heterogeneously mixed composition includes QH and one or more other components, and the concentration distribution of the QH is non-uniform and biased.
• a non-uniformly mixed mixed composition can be obtained, for example, by adding QH to one or more other ingredients such as food ingredients.
• the composition is a multi-phase composition
• a first phase comprising QH and a second phase comprising one or more other ingredients, placed in contact with each other.
• Said multi-phase composition as a whole can be a food, cosmetic or pharmaceutically acceptable composition, and if the first and second phases are separable, at least the first phase comprises food, It can be a cosmetically or pharmaceutically acceptable composition.
• the first phase includes QH Form I type crystals, QH Form II type crystals, co-crystals composed of QH and one or more other compounds, amorphous solids of QH, and QH dissolved in a solvent and/or a lipid-soluble medium.
• the multiphase composition can be, for example, a laminate of the first phase and the second phase, or a structure in which one of the first phase and the second phase is supported by the other.
• a first phase consisting of a composition in which QH is dissolved in a solvent and / or a fat-soluble medium
• a second phase consisting of water or an aqueous solution immiscible with the first phase and wherein one of the first phase and the second phase is laminated on the other.
• a first phase composed of particles containing QH and a second phase composed of one or more other matrix-like components are included, and the second phase includes the first Those in which a phase is carried are included.
• Yet another example of the multi-phase composition comprises a first phase comprising QH and a second phase comprising a substance that releases water, such that the first phase and the second phase are in contact with each other. Placed items are listed.
• the content of QH in the composition is not particularly limited.
• the content of QH relative to the total mass of the composition may be, for example, 0.01% by mass or more, preferably 0.1% by mass or more, more preferably 1% by mass or more, for example 99% by mass or less. , preferably 90% by mass or less, more preferably 50% by mass or less.
• the temperature at which the composition is stored in the method according to the present embodiment is, for example, -25°C or higher and 50°C or lower, preferably -20°C or higher, -10°C or higher, 0°C or higher, and 4°C or higher. , 10°C or higher, 15°C or higher, 20°C or higher or 25°C or higher, preferably 45°C or lower or 40°C or lower. Said temperature may in particular be 25°C or 40°C.
• the period for storing the composition in the method according to the present embodiment is not particularly limited as long as it is a period from after manufacture to use of the product, and can be appropriately adjusted according to storage conditions such as temperature, but is preferably 3 days or more, 1 week or more, or 2 weeks or more, for example, 5 years or less, usually 3 years or less, preferably 2 years or less, more preferably 1 year or less, further preferably 6 months or less, further preferably 8 weeks It can be less than, most preferably less than 6 weeks, less than 5 weeks or less than 4 weeks.
• the composition When storing the composition in the method according to the present embodiment, it is preferable to store the composition in a container and store it as a sealed package in order to prevent volatilization of water.
• the package may contain a gas phase within the container, and the gas phase may be air.
• a package containing air as a gas phase can be manufactured at a lower cost than a package containing a gas phase of an inert gas such as nitrogen, which is preferable.
• a second embodiment of the present invention comprises: A method of inhibiting oxidation of QH, comprising: A method comprising storing a composition comprising QH and having a water activity of 0.50 or higher at 25°C.
• the oxidation of QH can be efficiently suppressed at low cost.
• the respective features and preferred aspects of the QH, the composition, and the step of preserving the composition are as described for the method according to the first embodiment.
• a third embodiment of the present invention is It relates to a composition containing QH and having a water activity of 0.50 or more at 25°C.
• Oxidation of QH in the form of a composition according to the present embodiment is effectively suppressed.
• composition according to this embodiment the QH and the characteristics and preferred aspects of each of the compositions are as described for the method according to the first embodiment.
• reduced coenzyme Q10 (trade name: Kaneka QH) manufactured by Kaneka Corporation was used as reduced coenzyme Q10 Form I type crystal (QH Form I type crystal).
• the weight ratio of reduced coenzyme Q10 to total coenzyme Q10 (that is, reduced coenzyme Q10/(oxidized coenzyme Q10+reduced coenzyme Q10)) is defined as the “QH ratio”.
• the QH ratio was obtained by the following HPLC analysis.
• the QH ratio at the end of the evaluation when the QH ratio at the start of the evaluation is 100 is defined as the “QH residual ratio”, and the QH residual ratio obtained from the following formula is the oxidation stability. was used as a measure of
• QH residual rate (%) 100 ⁇ QH ratio at the end of evaluation / QH ratio at the start of evaluation
• Example 1 Storage of QHForm II Crystals in High Water Activity Compositions
• 3 g of commercially available bread was placed in a glass bottle (volume: 33 ml).
• 0.1 g of the QH Form II type crystal obtained in Production Example was placed in the glass bottle so as to be in contact with the bread, and the glass bottle was sealed. After storing this package under the conditions of 40° C. and 75% relative humidity for 4 weeks, the QH residual rate was determined.
• the water activity at 25° C. of the composition consisting of 3 g of bread and 0.1 g of QHForm II crystals was 0.95.
• Example 1 The results obtained in Example 1 and Comparative Example 1 are summarized and shown in Table 1.
• Example 2 A package prepared in the same manner as in Example 1 was stored for 4 weeks under conditions of 25° C. and 60% relative humidity, and then the QH residual rate was determined.
• Example 3 In a chamber adjusted to a relative humidity of 50%, 0.1 g of the QHForm II crystal obtained in Production Example was placed in an aluminum laminate bag (volume: about 1000 ml) and sealed to prepare a package containing the QH Form II crystal. At this time, the water activity of the QHForm II type crystal in the package was 0.50. After that, the package was stored at 25° C. for 4 weeks, and then the QH residual rate was determined.
• Example 4 A package was produced in the same manner as in Example 3, except that a chamber adjusted to a relative humidity of 85% was used and the water activity of the QHForm II crystal was kept at 0.85. At this time, the water activity of the QHForm II type crystal in the package was 0.85. After storing the package at 25° C. for 4 weeks, the QH residual rate was determined.
• Example 6 3 g of a 0.04% hexaglycerin monolaurate aqueous solution and 0.1 g of QHForm I type crystals were placed in a glass bottle (volume: 33 ml) and mixed. After the glass bottle was sealed and stored for 4 weeks under conditions of 25° C. and 60% relative humidity, the residual QH ratio was determined. The water activity at 25° C. of the composition consisting of 3 g of 0.04% hexaglycerol monolaurate aqueous solution and 0.1 g of QHForm I type crystals was 1.00.
• Example 7 A package prepared in the same manner as in Example 5 was stored for 2 weeks under conditions of 40° C. and 75% relative humidity, and then the QH residual rate was determined.
• Example 8 A package prepared in the same manner as in Example 6 was stored for 2 weeks under conditions of 40° C. and 75% relative humidity, and then the QH residual rate was determined.
• Example 9 revealed that reduced coenzyme Q10 present in the MCT solution was stably maintained even when the layer of the MCT solution containing reduced coenzyme Q10 was in contact with water.
• Example 10 0.2 g of a co-crystal composed of QH and nicotinamide was packed in an open state in a package whose internal relative humidity was adjusted to 53%. At this time, the water activity of the cocrystal in the package was 0.53. After storing the package at 40° C. for 2 weeks, the QH residual rate was determined.
• Example 10 The results obtained in Example 10 and Comparative Example 3 are summarized and shown in Table 5.
• Table 5 reveals that QH present in co-crystals composed of QH and nicotinamide is also kept stable in compositions with a water activity of 0.50 or higher.
• a preferred range can be defined by arbitrarily combining the upper and lower limits of the numerical range
• a preferred range can be defined by arbitrarily combining the upper limits of the numerical range
• the lower limit of the numerical range Any combination of values can be used to define a preferred range.
• a numerical range represented using the symbol "-" includes the numerical values described before and after the symbol "-" as lower and upper limits, respectively.

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