JPWO2008129980A1 - Reduced coenzyme Q10-containing particulate composition and method for producing the same - Google Patents

Abstract

The present invention provides high oxidative stability and high living body in the fields of foods, functional nutritional foods, foods for specified health use, nutritional supplements, nutritional agents, animal drugs, beverages, feeds, cosmetics, pharmaceuticals, therapeutic drugs, preventive drugs, etc. It is an object of the present invention to propose a particulate composition containing reduced coenzyme Q10 having both absorbability, a method for producing the same, and a method for stabilizing the same. As a result of diligent research to solve the above problems, the present inventors have found that an oily component containing reduced coenzyme Q10 is a domain in a matrix containing a water-soluble excipient as a main component and water-soluble ascorbic acids. The particulate composition containing reduced coenzyme Q10, which is polydispersed and formed, is a composition having both high oxygen stability and high bioabsorbability, and completed the present invention. .

Description

  The present invention relates to a particulate composition containing reduced coenzyme Q10 and a method for producing the same. More specifically, the present invention realizes a particulate composition containing reduced coenzyme Q10 having both high oxidative stability and high oral absorbability, a method for producing the same, and high oxidative stability and high oral absorbability. The present invention relates to a preparation form.

  Coenzyme Q is an essential component widely distributed in living organisms from bacteria to mammals. In humans, it is known that the side chain of coenzyme Q has 10 repeating structures and coenzyme Q10 is the main component. Coenzyme Q10 is a physiological component that exists as a constituent component of the mitochondrial electron transport system in cells in the living body, and plays a role as a transport component in the electron transport system by repeating oxidation and reduction in the living body. .

  Coenzyme Q10 is known to exhibit energy production, membrane stabilization and antioxidant activity in living bodies, and its usefulness is wide. Coenzyme Q10 has an oxidized type and a reduced type, and it is known that about 40 to 90% is usually present in reduced form in vivo. Among the coenzymes Q10, oxidized coenzyme Q10 (also known as ubiquinone or ubidecalenone) is used for pharmaceutical use as a congestive heart failure drug, and for non-medical use as well as vitamins. Widely used as an agent.

  On the other hand, reduced coenzyme Q10 exhibits higher oral absorbability than oxidized coenzyme Q10, and is food, nutritional functional food, food for specified health use, nutritional supplement, nutritional supplement, animal drug, beverage, feed, pet food. It is an excellent compound effective as a cosmetic, pharmaceutical, therapeutic agent, prophylactic agent and the like. However, reduced coenzyme Q10 is easily oxidized to oxidized coenzyme Q10 by molecular oxygen, and reduced coenzyme Q10 is converted into food, nutritional functional food, food for specified health use, nutritional supplement, nutritional supplement, animal drug, Stabilization of beverages, feeds, pet foods, cosmetics, pharmaceuticals, therapeutics, preventives, etc. or their materials and compositions and / or handling after processing remains an important issue. During the above handling, it is extremely difficult to completely remove or block oxygen. Especially in heating during processing and long-term storage, the remaining or mixed oxygen has a great adverse effect, and the quality such as by-product of oxidized coenzyme Q10. Directly related to the problem of the surface.

  Thus, maintaining the reduced coenzyme Q10 stably (protecting from oxidation) is a very important issue, but research on a method and a composition for stably holding the reduced coenzyme Q10 up to now. There has been little done. Slightly described examples of a composition coexisting with a reducing agent and its production method (Patent Document 1: WO01 / 52822), an example of describing a stabilization method, a preserving method coexisting with a reducing agent, and a composition thereof (Patent Document 2: WO 03/32967) and an example in which reduced coenzyme Q10 is stabilized in oil and fat are only recognized (Patent Document 3: WO 03/62182).

In this patent document 1,
1) An effective amount of a reducing agent and an amount effective to dissolve the reduced coenzyme Q10 and the reducing agent in order to suppress oxidation of reduced coenzyme Q10 to oxidized coenzyme Q10 A composition comprising a surfactant or vegetable oil or a mixture thereof, and optionally a solvent,
2) A composition for oral administration in which the above composition is formulated into a gelatin capsule or tablet,
3) Further, a method for preparing the above-mentioned composition containing reduced coenzyme Q10 in situ using oxidized coenzyme Q10 and a reducing agent,
Is disclosed.

  However, Patent Document 1 does not have a detailed description regarding the quality and stabilizing effect of reduced coenzyme Q10 contained in the composition. Further, in the composition and the preparation method thereof in Patent Document 1, in order to provide a reaction field for reducing oxidized coenzyme Q10 to reduced coenzyme Q10, fat-soluble oxidized and reduced coenzyme Q10 is used as a reducing agent. It is necessary to dissolve it at the molecular level in the same phase as in the case of, and in fact, it is considered essential to use a fat-soluble reducing agent. Patent Document 2 describes the stabilization of reduced coenzyme Q10 by coexisting reduced coenzyme Q10 and ascorbic acids in the presence of a monovalent or divalent alcohol and / or a water-soluble solvent other than alcohol. , A storage method and the above composition are disclosed. However, the composition described in Patent Document 2 is a liquid composition, and as described in detail in the invention, the amount of solvent used is preferably 60% by weight or more in the total mixture. It can be said that the stability of Q10 depends on the solubility of reduced coenzyme Q10 and ascorbic acids in a solvent.

  Patent Document 3 discloses, as a method for protecting reduced coenzyme Q10 from oxidation, reduced coenzyme Q10 comprising oil and fat (but excluding olive oil) and / or polyol as a main component, and There is disclosed a method for stabilizing reduced coenzyme Q10, which is characterized in that the composition does not substantially inhibit the stabilization of reduced coenzyme Q10. In some cases, the stability of Q10 is not sufficient. In addition, ascorbic acids may be added to the composition, but the form is limited to a liquid composition as in Patent Document 2 because of its form.

  In addition, there are some prior art documents that disclose that an antioxidant such as ascorbic acid can be added to a composition containing reduced coenzyme Q10 (for example, Patent Document 4: WO05 / 097091). Since type coenzyme Q10 is fat-soluble, it is actually limited to use in fat-soluble antioxidants or in the case of water-soluble antioxidants in a solvent (for example, ethanol) system that dissolves both. It is done.

Thus, conventionally, when reducing coenzyme Q10 is stabilized using a reducing agent such as ascorbic acid or oxidized coenzyme Q10 is reduced to reduced coenzyme Q10, oxidized coenzyme Q10 is reduced. In order to provide a reaction field for reduction to coenzyme Q10,
1) Fat-soluble oxidized and / or reduced coenzyme Q10 is dissolved as homogeneously as possible in an oil-based component consisting of fat-soluble ascorbic acids, fats and oils, and / or a surfactant, and if necessary a fat-soluble solvent, Fat-soluble oxidized coenzyme Q10 and / or reduced coenzyme Q10 and a fat-soluble reducing agent are combined at the molecular level,
2) A large amount of a solvent (for example, ethanol) having a property of dissolving both oxidized coenzyme Q10 and / or reduced coenzyme Q10 and reducing agent is used, and oxidized coenzyme Q10 and / or reduced at the molecular level. Dissolving type coenzyme Q10 and reducing agent,
There was a need. That is, the composition as described above necessarily becomes a liquid composition, and its application range is limited.

Under such circumstances, there has been a demand for a reduced coenzyme Q10-containing composition that is particulate and stable to oxidation that can be used in various applications.
WO01 / 052822 WO03 / 32967 WO03 / 062182 WO05 / 097091

  In order to provide a solution to the above points, the present invention provides foods, nutritional functional foods, foods for specified health use, nutritional supplements, nutritional agents, animal drugs, beverages, feeds, pet foods, cosmetics, pharmaceuticals, therapeutic drugs, preventive drugs, etc. A particulate composition containing reduced coenzyme Q10 having both high oxidative stability and high oral absorption, a method for producing the same, and a formulation form for realizing high oxidative stability and high oral absorption It is an issue to propose.

  As a result of intensive studies to solve the above problems, the present inventors have found that an oily component containing reduced coenzyme Q10 forms a domain in a matrix containing water-soluble ascorbic acids and a water-soluble excipient. The polydispersed particulate composition is a composition having both high oxidative stability and high oral absorbability, and a manufacturing method and a preparation form for obtaining such a particulate composition are found. The invention has been completed.

That is, the present invention provides the following:
[1] A particulate composition in which an oily component (A) containing reduced coenzyme Q10 forms a domain and is polydispersed in a matrix containing a water-soluble excipient and water-soluble ascorbic acids.
[2] Water-soluble ascorbic acid is ascorbic acid, rhamno-ascorbic acid, arabo-ascorbic acid, gluco-ascorbic acid, fuco-ascorbic acid, glucohepto-ascorbic acid, xyllo-ascorbic acid, galacto-ascorbic acid, gulo-ascorbic acid The particulate composition according to [1], which is at least one selected from the group consisting of acids, allo-ascorbic acid, erythro-ascorbic acid, 6-desoxyascorbic acid and salts thereof.
[3] The particulate composition according to [1] or [2], wherein the sphericity is 0.8 or more.
[4] The particulate composition according to any one of [1] to [3], wherein 10% by weight or more of the reduced coenzyme Q10 in the particulate composition is not in a crystalline state.
[5] The particulate composition according to any one of [1] to [4], wherein the oil component (A) forms 5 or more domains and is polydispersed.
[6] The ratio of reduced coenzyme Q10 and water-soluble ascorbic acid in the particulate composition is in the range of 100: 1 to 1: 5 by weight, [1] to [1] [5] The particulate composition according to any one of [5].
[7] Any of [1] to [6], wherein the water-soluble excipient is at least one selected from the group consisting of a water-soluble polymer, a surfactant (C), a sugar, and a yeast cell wall. A particulate composition as described in 1.
[8] The water-soluble polymer is gum arabic, gelatin, agar, starch, pectin, carrageenan, casein, dried egg white, curdlan, alginic acid, soybean polysaccharide, pullulan, cellulose, xanthan gum, carmellose salt, and polyvinylpyrrolidone. The particulate composition according to [7], which is one or more selected from the group consisting of:
[9] One or more surfactants (C) selected from the group consisting of glycerin fatty acid esters, sucrose fatty acid esters, sorbitan fatty acid esters, polyoxyethylene sorbitan fatty acid esters, lecithins and saponins The particulate composition according to [7].
[10] The particulate composition according to [7], wherein the sugar is at least one selected from the group consisting of monosaccharides, disaccharides, oligosaccharides, sugar alcohols, and polysaccharides.
[11] The oil component (A) containing reduced coenzyme Q10 contains 5 to 100% by weight of coenzyme Q10, 0 to 95% by weight of fat and oil, and 0 to 95% by weight of surfactant (D). The particulate composition according to any one of [1] to [10], which is contained.
[12] Glycerin fatty acid esters, polyglycerol esters, sucrose fatty acid esters, sorbitan fatty acid esters, polyoxyethylene sorbitan fatty acid esters and propylene glycol fatty acid esters having a surfactant (D) of HLB of 10 or less And the particulate composition according to [11], which is at least one selected from the group consisting of lecithins.
[13] The particulate composition according to any one of [1] to [12], wherein the content of reduced coenzyme Q10 in the particulate composition is 1 to 70% by weight.
[14] The particulate composition according to any one of [1] to [13], wherein the volume average particle diameter is 1 to 1000 μm.
[15] The particulate composition according to any one of [1] to [14], wherein the domain formed by the oily component (A) containing reduced coenzyme Q10 has an average particle diameter of 0.01 to 50 μm. object.
[16] The retention rate of reduced coenzyme Q10 in the particulate composition after storage for 30 days under light-shielding conditions at 40 ° C. in air is 80% by weight or more [1] to [15] The particulate composition described.
[17] A preparation obtained by processing the particulate composition according to any one of [1] to [16].
[18] A reduced type composition comprising the particulate composition according to any one of [1] to [16] or the preparation according to [17] in an ambient environment having a relative humidity of 90% or less. A method for stabilizing a particulate composition or preparation containing enzyme Q10.
[19] The particulate composition according to any one of [1] to [16] or the preparation according to [17] is packed and packed with a glass, plastic and / or metal material. A method for stabilizing a particulate composition or preparation containing reduced coenzyme Q10.
[20] The stabilization method according to [18] or [19], wherein a moisture-proofing agent is used in combination.
[21] An oil-in-water emulsion composition is prepared from an aqueous solution containing water-soluble ascorbic acids and a water-soluble excipient and an oily component (a) containing coenzyme Q10, and then in the oil-in-water emulsion composition The manufacturing method of the particulate composition containing reduced coenzyme Q10 characterized by removing the water | moisture content of this.
[22] The production method according to [21], wherein reduced coenzyme Q10 is used as coenzyme Q10 contained in the oily component (a).
[23] In the process of producing a particulate composition using oxidized coenzyme Q10 or a mixture of oxidized coenzyme Q10 and reduced coenzyme Q10 as coenzyme Q10 contained in the oily component (a), The production method according to [21], wherein at least a part of oxidized coenzyme Q10 in coenzyme Q10 is reduced to reduced coenzyme Q10.
[24] Water-soluble ascorbic acid is ascorbic acid, rhamno-ascorbic acid, arabo-ascorbic acid, gluco-ascorbic acid, fuco-ascorbic acid, glucohepto-ascorbic acid, xyllo-ascorbic acid, galacto-ascorbic acid, gulo-ascorbic acid The production method according to any one of [21] to [23], which is one or more selected from the group consisting of acids, allo-ascorbic acid, erythro-ascorbic acid, 6-desoxyascorbic acid and salts thereof .
[25] The oil-in-water emulsion composition is suspended in the oil component (B), and then the water in the oil-in-water emulsion composition is removed in the oil component (B). 21] to [24].
[26] The production method according to [25], wherein the oil component (B) contains 5 to 99.99% by weight of fat and oil and 0.01 to 95% by weight of the surfactant (E).
[27] The surfactant (E) is composed of glycerin fatty acid esters, polyglycerin esters, sucrose fatty acid esters, sorbitan fatty acid esters, polyoxyethylene sorbitan fatty acid esters, and lecithins having an HLB of 10 or less. The production method according to [26], which is one or more selected from the group.
[28] The oil-in-water emulsion composition is spray-dried in a gas phase to remove moisture in the oil-in-water emulsion composition, according to any one of [21] to [24] Manufacturing method.
[29] The production method according to any one of [21] to [28], wherein the obtained granular composition has a sphericity of 0.8 or more.
[30] The production method according to any one of [21] to [29], wherein 1 to 500 parts by weight of water-soluble ascorbic acid is used with respect to 100 parts by weight of coenzyme Q10.
[31] Any of [21] to [30], wherein the water-soluble excipient is at least one selected from the group consisting of a water-soluble polymer, a surfactant (C), a sugar, and a yeast cell wall. The manufacturing method as described in.
[32] The water-soluble polymer is gum arabic, gelatin, agar, starch, pectin, carrageenan, casein, dried egg white, curdlan, alginic acids, soybean polysaccharide, pullulan, celluloses, xanthan gum, carmellose salt, and polyvinylpyrrolidone. The production method according to [31], which is one or more selected from the group consisting of:
[33] One or more surfactants (C) selected from the group consisting of glycerin fatty acid esters, sucrose fatty acid esters, sorbitan fatty acid esters, polyoxyethylene sorbitan fatty acid esters, lecithins and saponins The production method according to [31].
[34] The production method according to [31], wherein the sugar is at least one selected from the group consisting of monosaccharides, disaccharides, oligosaccharides, sugar alcohols, and polysaccharides.
[35] The oil component (a) containing coenzyme Q10 contains 5 to 100% by weight of coenzyme Q10, 0 to 95% by weight of fat and oil, and 0 to 95% by weight of surfactant (D). , [21] to [34].
[36] Glycerin fatty acid esters, polyglycerol esters, sucrose fatty acid esters, sorbitan fatty acid esters, polyoxyethylene sorbitan fatty acid esters and propylene glycol fatty acid esters whose surfactant (D) is HLB of 10 or less And the production method according to [35], which is at least one selected from the group consisting of lecithins.

  The present invention relates to a particulate composition containing reduced coenzyme Q10 having both high oxidative stability and high oral absorption, a method for producing the same, and a formulation form for realizing high oxidative stability and high oral absorption I will provide a. The particulate composition containing the reduced coenzyme Q10 of the present invention and the preparation obtained by processing it are particularly excellent in oxidation stability under high humidity.

The conceptual diagram of the soft capsule formulation obtained by filling the mixed slurry which suspended the particulate composition of this invention in the oil-based component (F). The scanning electron micrograph of the external appearance of the particulate composition obtained in Example 1. 2 is a scanning electron micrograph of the cross section of the particulate composition obtained in Example 1. FIG. Comparison of oral absorbability between the particulate composition obtained in Example 7 and reduced coenzyme Q10 obtained in Production Example 1.

  First, the particulate composition of the present invention will be described. In the particulate composition of the present invention, an oil component (A) containing reduced coenzyme Q10 forms a domain and is polydispersed in a matrix containing a water-soluble excipient and water-soluble ascorbic acids. It is a particulate composition characterized by this.

  The reduced coenzyme Q10 contained in the granular particle composition of the present invention is represented by the following formula (1).

  As described above, coenzyme Q10 has a reduced form and an oxidized form, but the particulate composition of the present invention contains at least reduced coenzyme Q10 in coenzyme Q10. The reduced coenzyme Q10 contained in the particulate composition of the present invention may be reduced type alone or coenzyme Q10 which is a mixture of oxidized coenzyme Q10 and reduced coenzyme Q10. good. When the particulate composition of the present invention contains both reduced coenzyme Q10 and oxidized coenzyme Q10, the reduced coenzyme Q10 is the total amount of coenzyme Q10 (that is, reduced coenzyme Q10 and oxidized coenzyme). The ratio of the total amount of enzyme Q10) is not particularly limited, but is, for example, about 20% by weight or more, usually about 40% by weight or more, preferably about 60% by weight or more, more preferably about 80% by weight or more, especially about 90%. % By weight, above all about 96% by weight. The upper limit is 100% by weight and is not particularly limited, but is usually about 99.9% by weight or less.

  In the present specification, when simply described as “coenzyme Q10”, unless otherwise specified, a mixture of oxidized coenzyme Q10 and reduced coenzyme Q10 is shown. When the enzyme Q10 is present alone (or used alone), it may mean reduced coenzyme Q10 alone or oxidized coenzyme Q10 alone, respectively.

  The reduced coenzyme Q10 contained in the particulate composition of the present invention may be derived from the reduced coenzyme Q10 used as a raw material when preparing the particulate composition, or the particulate composition The oxidized coenzyme Q10 used as a raw material (or part thereof) for preparing a product may be reduced coenzyme Q10 reduced in the production process.

  When reduced coenzyme Q10 is used as a raw material when preparing the particulate composition of the present invention, the reduced coenzyme Q10 is synthesized, for example, as described in JP-A-10-109933. After obtaining coenzyme Q10 which is a mixture of oxidized coenzyme Q10 and reduced coenzyme Q10 by a conventionally known method such as fermentation or extraction from natural products, the reduced form in the effluent is obtained using chromatography. It can be produced by a method of concentrating the coenzyme Q10 section. In this case, the oxidized coenzyme Q10 contained in the coenzyme Q10 is reduced with a common reducing agent such as sodium borohydride, sodium hydrosulfite (sodium hyposulfite), and then chromatographed. Concentration by may be performed. Reduced coenzyme Q10 can be obtained by allowing the above reducing agent to act on existing high-purity oxidized coenzyme Q10.

  Preferably, the existing high-purity oxidized coenzyme Q10 or coenzyme Q10, which is a mixture of oxidized coenzyme Q10 and reduced coenzyme Q10, is replaced with a common reducing agent such as hydrosulfite sodium (sodium hyposulfite ), Obtained by reduction using sodium borohydride, ascorbic acid or the like, and more preferably, existing high-purity oxidized coenzyme Q10, or oxidized coenzyme Q10 and reduced coenzyme Q10. Is obtained by reducing coenzyme Q10, which is a mixture of the above, with ascorbic acids.

  The water-soluble ascorbic acid contained in the matrix portion of the particulate composition of the present invention is not particularly limited as long as it is a water-soluble ascorbic acid. For example, ascorbic acid, rhamo-ascorbic acid, arabo-ascorbic acid, gluco -Ascorbic acid, fuco-ascorbic acid, glucohepto-ascorbic acid, xyllo-ascorbic acid, galacto-ascorbic acid, gulo-ascorbic acid, allo-ascorbic acid, erythro-ascorbic acid, 6-desoxyascorbic acid, etc. Salt. These may be L-form, D-form, or racemate. Specifically, L-ascorbic acid, sodium L-ascorbate, calcium L-ascorbate, D-arabo-ascorbic acid, etc. Can be mentioned. In the present invention, any of the above water-soluble ascorbic acids can be suitably used, but L-ascorbic acid or D-arabo-ascorbic acid is preferred from the viewpoints of stability and versatility of reduced coenzyme Q10. Needless to say, a plurality of these water-soluble ascorbic acids may be used in combination.

  The content of the water-soluble ascorbic acids in the particulate composition of the present invention is not particularly limited as long as it is an amount effective for improving the oxidative stability of reduced coenzyme Q10 contained in the particulate composition. Although not, for the purpose of sufficiently improving the stability of reduced coenzyme Q10 in the obtained particulate composition, water-soluble ascorbic acids with respect to 100 parts by weight of reduced coenzyme Q10 in the particulate composition The content ratio is preferably 1 part by weight or more, more preferably 2 parts by weight or more, still more preferably 5 parts by weight or more, and particularly preferably 10 parts by weight or more.

  On the other hand, the upper limit of the content of the water-soluble ascorbic acids in the particulate composition of the present invention is not particularly limited in achieving the object of the present invention, but from the viewpoint of economy and the like, The content of reduced coenzyme Q10 is preferably 500 parts by weight or less, more preferably 300 parts by weight or less, still more preferably 250 parts by weight or less, and particularly preferably 200 parts by weight or less.

  That is, the ratio of the reduced coenzyme Q10 and the water-soluble ascorbic acid in the particulate composition is preferably in the range of 100: 1 to 1: 5 by weight, and is 50: 1 to 1: 3. More preferably, it is more preferably 20: 1 to 1: 2.5, particularly preferably 10: 1 to 1: 2.

  The matrix in the present invention is to retain the oily component (A) containing the reduced coenzyme Q10 in the particulate composition to form a particle shape. The matrix in the present invention contains a water-soluble excipient and a water-soluble ascorbic acid as constituent components, and preferably contains a water-soluble excipient as a main component and at least a water-soluble ascorbic acid as another component. To do. Further, the matrix may be composed only of a water-soluble excipient and water-soluble ascorbic acid.

  The content of the water-soluble excipient in the matrix component is not particularly limited, but is preferably 50% by weight or more, more preferably 55% by weight or more, further preferably 60% by weight or more, and particularly preferably 80% by weight or more. . The upper limit of the content of the water-soluble excipient in the matrix component is not particularly limited, and as described above, all the matrix components other than the water-soluble ascorbic acids may be water-soluble excipients. That is, the upper limit of the total amount of the water-soluble excipient and the water-soluble ascorbic acid in the matrix component is 100% by weight, and when the other component is included as the matrix component, it is usually 99.9% by weight or less.

  The water-soluble excipient that is a component of the matrix of the particulate composition of the present invention is not particularly limited, but is selected from the group consisting of water-soluble polymers, surfactants (C), sugars, and yeast cell walls. It is preferable that it is 1 type or those mixtures. The water-soluble excipient is not particularly limited as long as it is acceptable for food, cosmetics, and pharmaceutical use, but is preferably acceptable for food.

  Examples of the water-soluble polymer include gum arabic, gelatin, agar, starch, pectin, carrageenan, casein, casein compound, dried egg white, curdlan, alginic acid, soybean polysaccharide, pullulan, cellulose, xanthan gum, carmellose salt (Such as carmellose sodium or carmellose calcium), sugar esters of higher fatty acids, tragacanth, milk, etc., water-soluble polymers mainly composed of amino acids or / and sugars, or polyvinylpyrrolidone, alone or 2 It can be used as a mixture of more than one kind.

  Among them, gum arabic, gelatin, agar, starch, pectin, carrageenan, casein, dried egg white, curdlan, alginic acids, soy polysaccharides, pullulan, celluloses, xanthan gum, carmellose salt, and polyvinylpyrrolidone are preferable. Gum arabic, gelatin, and soybean polysaccharide are more preferably used from the viewpoint of obtaining a particulate composition having both handleability or high oxidative stability and high bioabsorbability, which is the object of the present invention.

  The surfactant (C) is not particularly limited as long as it is acceptable for foods, cosmetics, and pharmaceuticals, but is particularly preferably acceptable for foods. For example, glycerin fatty acid esters, sucrose fatty acid esters, Examples include sorbitan fatty acid esters, polyoxyethylene sorbitan fatty acid esters, lecithins, and saponins. Needless to say, in the present invention, these can be used alone or as a mixture of two or more.

  Examples of the glycerin fatty acid esters include monoglycerin fatty acid organic acid esters, polyglycerin fatty acid esters, polyglycerin condensed ricinoleic acid esters, and the like. Examples of monoglycerin fatty acid organic acid esters include monoglycerin stearic acid citrate, monoglycerin stearic acid acetate, monoglycerin stearic acid succinic acid ester, monoglycerin caprylic acid succinic acid ester, monoglycerin stearic acid lactate, mono Examples thereof include glyceryl stearic acid diacetyl tartaric acid ester. Examples of the polyglycerol fatty acid ester include those having an average degree of polymerization of 2 to 10 and a constituent fatty acid having 6 to 22 carbon atoms, preferably 6 to 18 carbon atoms. Examples of the polyglycerol condensed ricinoleic acid ester include those having an average degree of polymerization of polyglycerol of 2 to 10 and an average degree of condensation of polyricinoleic acid (average of the number of condensation of ricinoleic acid) of 2 to 4.

  Examples of the sucrose fatty acid esters include those obtained by esterifying one or more hydroxyl groups of sucrose with fatty acids having 6 to 22 carbon atoms, preferably 6 to 18 carbon atoms.

  Examples of the sorbitan fatty acid esters include those obtained by esterifying one or more hydroxyl groups of sorbitans with fatty acids having 6 to 22 carbon atoms, preferably 6 to 18 carbon atoms.

  As the polyoxyethylene sorbitan fatty acid esters, at least one hydroxyl group of sorbitans is substituted with a polyoxyethylene chain, and at least one of the existing hydroxyl groups has 6 to 22 carbon atoms, preferably What was esterified with the fatty acid of 6-18 is mentioned.

  Examples of the lecithins include egg yolk lecithin, purified soybean lecithin, phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, sphingomyelin, dicetylphosphate, stearylamine, phosphatidylglycerol, phosphatidic acid, phosphatidylinositolamine, cardiolipin, ceramide phosphorylethanolamine, Examples thereof include ceramide phosphorylglycerol, enzyme-decomposed lecithin (lysolecithin), and a mixture thereof.

  Examples of the saponins include Enjusaponin, Quillaja Saponin, Soy Saponin, Yucca Saponin and the like.

  Among the above surfactants (C), a particulate composition that can stably emulsify an oily component containing reduced coenzyme Q10, and has high oxygen stability and high bioabsorbability, which are the objects of the present invention. From the viewpoint of obtaining a product, the surfactant (C) is preferably a hydrophilic surfactant, for example, a surfactant having an HLB of 4 or more, usually an HLB of 6 or more, preferably an HLB of 8 or more. Can be used.

  Specific examples of such surfactants include monoglycerol fatty acid organic acid esters such as monoglycerol stearic acid citrate and monoglycerol stearate diacetyltartaric acid; triglycerol monolaurate and triglycerol monomyristate , Triglycerol monooleate, triglycerol monostearate, pentaglycerol monomyristate, pentaglycerol trimyristate, pentaglycerol monooleate, pentaglycerol trioleate, pentaglycerol monostearate, Pentaglycerin tristearate, pentaglycerin monostearate, hexaglycerin monocaprylate, hexa Glycerin dicaprylate, hexaglycerol monolaurate, hexaglycerol monomyristate, hexaglycerol monooleate, hexaglycerol monostearate, decaglycerol monolaurate, decaglycerol monomyristate, decaglycerol monooleate Esters, polyglycerin fatty acid esters such as decaglycerin monopalmitate, decaglycerin monostearate, decaglycerin distearate; tetraglycerin condensed ricinoleic acid ester, pentaglycerin condensed ricinoleic acid ester, hexaglycerin condensed ricinoleic acid ester, di Polyglycerin condensed ricinolein such as glycerin condensed ricinoleate Esters; sorbitan fatty acid esters such as sorbitan monostearate and sorbitan monooleate; sucrose fatty acid esters such as sucrose palmitate and sucrose stearate; soybean lecithin, egg yolk lecithin, enzymatically decomposed lecithin, etc. Lecithins; saponins such as Enjusaponin, Quillaja Saponin, Soy Saponin, Yucca Saponin and the like.

  In the present invention, the surfactant (C) is preferably used in combination with other water-soluble excipients.

  The sugar is not particularly limited as long as it is acceptable for food. Examples thereof include monosaccharides such as glucose, fructose, galactose, arabinose, xylose, and mannose; disaccharides such as maltose, sucrose, and lactose; fructo-oligosaccharide, soybean Oligosaccharides such as oligosaccharide, galactooligosaccharide, and xylooligosaccharide; sugar alcohols such as sorbitol, maltitol, erythritol, lactitol, and xylitol; polysaccharides such as dextrin; and the like can be preferably used.

  The dextrin may be any decomposition product of starch, and any of low molecular dextrins and high molecular dextrins can be suitably used, and is not particularly limited. However, from the viewpoint of solubility in the aqueous layer, the dextrose equivalent is usually 40 or less, preferably 35 or less, more preferably 30 or less, and usually 1 or more, preferably 2 or more, more preferably 5 or more. Dextrin can be preferably used. Also, the dextrin may be maltodextrin, cyclodextrin, cluster dextrin or the like.

  Examples of the yeast cell wall include a cell wall of brewer's yeast.

  In the present invention, it is preferable to use a combination of a water-soluble polymer and a sugar as the water-soluble excipient, and gum arabic is selected as the water-soluble polymer, and sucrose and / or dextrin is selected as the sugar. It is particularly preferable to combine them. When the water-soluble polymer and saccharide are used in combination, the weight ratio of the water-soluble polymer and saccharide is not particularly limited, but the ratio of the water-soluble polymer to the total amount of saccharide is usually 25% by weight. Or more, preferably 40% by weight or more, more preferably 50% by weight or more, particularly preferably 60% by weight or more, and usually 99% by weight or less, preferably 95% by weight or less, more preferably 90% by weight or less, Particularly preferred is 85% by weight or less.

  The oil component (A) containing reduced coenzyme Q10 that forms the domain part of the particulate composition of the present invention includes (1) reduced coenzyme Q10 alone, or reduced coenzyme Q10 and oxidized coenzyme. Coenzyme Q10 which is a mixture of enzyme Q10 may be used alone, or (2) reduced coenzyme Q10 or coenzyme Q10 and a mixture of oil and fat and / or surfactant (D). When it is a mixture of reduced coenzyme Q10 or coenzyme Q10 and oil or fat and / or surfactant (D) as an oil component (A), it is mixed visually and uniformly when heated and melted at 50 ° C. or higher. The oily component obtained is preferred. From the viewpoint of maintaining a high content of reduced coenzyme Q10 in the oil component (A), the above (1) is preferable.

  The oil and fat used when the oil and fat component (A) is (2) is not particularly limited, and may be, for example, natural oil or fat from animals or plants, or synthetic oil or processed oil or fat. More preferably, it is acceptable for food, cosmetics or medicine. For example, as vegetable oils and fats, for example, palm 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, sesame oil, Examples include cottonseed oil, sunflower seed oil, kapok oil, evening primrose oil, shea fat, monkey fat, cacao fat, sesame oil, safflower oil, olive oil, etc. Examples of animal fats include pork fat, milk fat, fish oil, beef tallow Furthermore, the fats and oils (for example, hardened oil) which processed these by fractionation, hydrogenation, transesterification, etc. can also be mentioned. Needless to say, medium chain fatty acid triglycerides (MCT) may also be used. Moreover, you may use these mixtures. Examples of the medium-chain fatty acid triglyceride include triglycerides in which the fatty acid has 6 to 12 carbon atoms, preferably 8 to 12 carbon atoms.

  Of the above oils and fats, vegetable oils, synthetic oils and processed oils and fats are preferable from the viewpoint of ease of handling, odor, and the like. Examples include coconut oil, palm oil, palm kernel oil, rapeseed oil, rice oil, soybean oil, cottonseed oil, safflower oil, olive oil, MCT, and the like.

  Examples of the surfactant (D) used when the oil and fat component (A) is (2) above include glycerin fatty acid esters, polyglycerin esters, sucrose fatty acid esters, sorbitan fatty acid esters, polyoxy Examples include, but are not limited to, ethylene sorbitan fatty acid esters, propylene glycol fatty acid esters, and lecithin.

  Examples of such glycerin fatty acid esters include monoglycerides and diglycerides in which the fatty acid has 6 to 22 carbon atoms, preferably 6 to 18 carbon atoms.

  Examples of the polyglycerin esters include polyglycerin mainly composed of polyglycerin having a polymerization degree of 2 to 10, and one or more hydroxyl groups of polyglycerin each having 6 to 22, preferably 6 to 18 carbon atoms. What esterified fatty acid is mentioned.

  Examples of the sucrose fatty acid esters include those obtained by esterifying one or more hydroxyl groups of sucrose with a fatty acid having 6 to 22 carbon atoms, preferably 6 to 18 carbon atoms.

  Examples of sorbitan fatty acid esters include those obtained by esterifying one or more hydroxyl groups of sorbitans with fatty acids having 6 to 22 carbon atoms, preferably 6 to 18 carbon atoms.

  As polyoxyethylene sorbitan fatty acid esters, at least one hydroxyl group of sorbitans is substituted with a polyoxyethylene chain, and one or more of the existing hydroxyl groups have 6 to 22 carbon atoms, preferably What was esterified with the fatty acid of 6-18 is mentioned.

  Examples of the propylene glycol fatty acid esters include monoglycerides and diglycerides in which the fatty acid has 6 to 22 carbon atoms, preferably 6 to 18 carbon atoms.

  Examples of lecithin include egg yolk lecithin, purified soybean lecithin, phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, sphingomyelin, dicetylphosphate, stearylamine, phosphatidylglycerol, phosphatidic acid, phosphatidylinositolamine, cardiolipin, ceramide phosphorylethanolamine, ceramide Examples include phosphorylglycerol, enzyme-decomposed lecithin (lysolecithin), and mixtures thereof.

  Among the above surfactants (D), a particulate composition having good compatibility with reduced coenzyme Q10, or high oxidation stability and high bioabsorbability, which is the object of the present invention, is obtained. In view of this, lipophilic surfactants are preferred, and for example, surfactants having an HLB of 10 or less, preferably 8 or less, more preferably 6 or less, and even more preferably 5 or less can be used. However, lecithins are not limited to the HLB and can be preferably used.

Specifically, as such a surfactant,
Monoglycerol monostearate, monoglycerol monooleate, monoglycerol monomyristate, monoglycerol monocaprylate, monoglycerol monolaurate, monoglycerol monobehenate, monoglycerol monoerucate, etc. Monoglycerin mono fatty acid ester;
Monoglycerol difatty acid esters such as monoglycerol distearate, monoglycerol dioleate, monoglycerol dicaprylate, monoglycerol dilaurate;
Monoglycerol stearate citrate, Monoglycerol stearate acetate, Monoglycerol coconut palm oil acetate, Monoglycerol stearate succinate, Monoglycerol caprylate succinate, Monoglycerol stearate lactate, Monoglycerol stearate Monoglycerol fatty acid organic acid esters such as diacetyl tartaric acid ester;
Monoglycerin fatty acid obtained using various fats such as monoglycerin beef tallow fatty acid ester, monoglycerin rapeseed hardened oil fatty acid ester, monoglycerin soybean hardened oil fatty acid ester, monoglycerin cottonseed oil fatty acid ester, monoglycerin safflower oil fatty acid ester ester;
Polyglycerol fatty acid esters such as esters of polyglycerin having an average degree of polymerization of 2 to 10 and fatty acids having 6 to 22 carbon atoms, preferably 6 to 18 carbon atoms, and polyglycerin having an average degree of polymerization of 2 to 10 and a degree of condensation of 2 to 4 Glycerin fatty acid esters such as polyglycerin condensed ricinoleic acid ester such as ester with polyricinoleic acid;
Propylene glycol fatty acid esters such as propylene glycol monostearate, propylene glycol monooleate, and propylene glycol monolaurate;
Sorbitan fatty acid esters such as sorbitan distearate, sorbitan tristearate, sorbitan sesquioleate, sorbitan dioleate, and sorbitan trioleate;
Polyoxyethylene sorbitan monooleate, polyoxyethylene sorbitan fatty acid esters such as polyoxyethylene sorbitan difatty acid ester;
In addition, one or a mixture of two or more selected from lecithins such as soybean lecithin, egg yolk lecithin, and enzymatically decomposed lecithin can be mentioned. Among them, preferred are glycerin fatty acid esters and / or lecithins, and more preferred are monoglycerin monofatty acid esters, monoglycerin difatty acid esters, monoglycerin fatty acid organic acid esters (particularly monoglycerin fatty acid acetate, monoglycerin coconut hardened oil). Acetate), polyglycerin fatty acid ester (especially ester of polyglycerin having an average polymerization degree of 2 to 10 and fatty acid having 6 to 22 carbon atoms, preferably 6 to 18 carbon atoms) or polyglycerin condensed ricinoleic acid ester (especially an average degree of polymerization of 2). -10 ester of polyglycerin and polyricinoleic acid having a condensation degree of 2 to 4, and more preferably monoglycerin fatty acid organic acid ester (particularly monoglycerin fatty acid acetate ester, monoglycerin coconut oil hardened oil acetate ester). Specific examples include 50% acetylated product of monoglycerin monostearate, fully acetylated product of hardened palm oil monoglyceride, soybean lecithin, egg yolk lecithin, enzymatically decomposed lecithin and the like. Any of the above surfactants can be used alone or in admixture of two or more.

  In addition to the above, in the present invention, oil-soluble components (A) such as waxes, fatty acids and ester derivatives thereof can be contained in the oil-based component (A) according to various purposes.

  Examples of the waxes include food waxes such as beeswax, mole, cadilla wax, rice bran wax, carmauba wax, and snow wax.

  Examples of the fatty acid and ester derivatives thereof include caprylic acid, capric acid, lauric acid, myristic acid, palmitic acid, stearic acid, oleic acid, behenic acid and esters thereof such as methyl ester and ethyl ester thereof. However, it is not limited to these.

  The composition of the oily component (A) containing reduced coenzyme Q10 in the particulate composition of the present invention is not particularly limited, but the high content of reduced coenzyme Q10 in the particulate composition is maintained. From the viewpoint, the content of coenzyme Q10 in the oily component (A) is preferably 5% by weight or more, more preferably 20% by weight or more, further preferably 40% by weight or more, particularly preferably 50% by weight or more, Particularly preferred is 60% by weight or more. Needless to say, the upper limit of the content of coenzyme Q10 in the oil component (A) is 100% by weight, and it is not always necessary to use an oil or a surfactant other than coenzyme Q10 as the oil component (A). When using fats and oils and surfactants, the upper limit is about 99.99% by weight.

  The oil content in the oil component (A) is preferably 95% by weight or less, more preferably 75% by weight or less, still more preferably 50% by weight or less, and particularly preferably 30% by weight or less. Although it is possible to contain 0% by weight, that is, no fat or oil, the lower limit in the case of inclusion is about 0.01% by weight.

  The content of the surfactant (D) in the oil component (A) is preferably 95% by weight or less, more preferably 75% by weight or less, still more preferably 50% by weight or less, particularly preferably 30% by weight. The lower limit is 0% by weight, that is, it is possible to contain no surfactant (D) at all. However, the lower limit in the case of inclusion is about 0.01% by weight.

  That is, the composition of the oil component (A) preferably contains 5 to 100% by weight of coenzyme Q10, 0 to 95% by weight of fat and oil, and 0 to 95% by weight of surfactant (D). More preferably, it contains 20 to 100% by weight of coenzyme Q10, 0 to 75% by weight of fats and oils, and 0 to 75% by weight of surfactant (D), and 40 to 100% by weight of coenzyme Q10. More preferably 0 to 50% by weight of fat and oil, 0 to 50% by weight of surfactant (D), 50 to 100% by weight of coenzyme Q10, 0 to 50% by weight of fat and oil, and It is particularly preferable to contain 0 to 50% by weight of surfactant (D), 55 to 100% by weight of coenzyme Q10, 0 to 45% by weight of fat and oil, and 0 to 45% by weight of surfactant. (D) is particularly preferred, comprising 60 to 100% by weight Enzyme Q10,0~40 wt% fat, and most preferably consisting of 0-40% by weight of a surfactant (D).

  When the content of the coenzyme Q10 in the oil component (A) is less than 5% by weight, the content of the reduced coenzyme Q10 contained in the particulate composition is also reduced as a result. When orally administering the reduced coenzyme Q10, it is necessary to ingest a large amount of the particulate composition. Needless to say, the coenzyme Q10 as the component of the oil component (A) may be reduced coenzyme Q10 alone or a mixture of reduced coenzyme Q10 and oxidized coenzyme Q10. In the case of a mixture of Q10 and oxidized coenzyme Q10, the ratio of reduced coenzyme Q10 in coenzyme Q10 is preferably higher.

  The content of reduced coenzyme Q10 in the particulate composition of the present invention is not particularly limited, but is usually 1% by weight or more, preferably 5% by weight or more, more preferably 10% by weight or more, and usually It is 70% by weight or less, preferably 60% by weight or less, more preferably 55% by weight or less. That is, the content of reduced coenzyme Q10 in the particulate composition of the present invention is preferably in the range of 1 to 70% by weight, more preferably in the range of 5 to 60% by weight, Most preferred is in the range of 55% by weight.

  When the content of reduced coenzyme Q10 in the particulate composition is less than 1% by weight, it is necessary to ingest a large amount of the particulate composition when orally administering a predetermined amount of reduced coenzyme Q10. It becomes. On the other hand, the upper limit of the reduced coenzyme Q10 content in the particulate composition is not particularly limited as long as it can provide high oxidation stability, which is one of the objects of the present invention, but the reduced form in the particulate composition is not limited. When the content of coenzyme Q10 is more than 70% by weight, it tends to be difficult to maintain high oxidative stability.

  The average particle size of the domain formed by the oily component (A) containing reduced coenzyme Q10 in the particulate composition of the present invention is not particularly limited as long as the object of the present invention can be achieved, but 0.01 It is preferably in the range of ˜50 μm, more preferably in the range of 0.01 to 20 μm, and most preferably in the range of 0.01 to 10 μm. When the average particle diameter of the domain formed by the oily component (A) containing reduced coenzyme Q10 is larger than 50 μm, the oral absorbability of reduced coenzyme Q10 in the particulate composition tends to decrease. .

  On the other hand, when the average particle diameter of the domain formed by the oily component (A) containing reduced coenzyme Q10 is smaller than 0.01 μm, in order to maintain the stability of the emulsified droplets in the production process, an excessive amount There may occur a problem that the surfactant (C) and / or the surfactant (D) is required or an excessive load is required on the emulsifying device. In addition, the average particle diameter of the domain formed by the oil component (A) containing reduced coenzyme Q10 in the particulate composition is oil-in-water emulsification when produced using the production method of the present invention described later. By controlling the emulsified particle size of the oil component (a) when adjusting the composition, the desired average particle size can be obtained.

  The average particle diameter of the domain formed by the oily component (A) containing reduced coenzyme Q10 in the particulate composition of the present invention is such that the particulate composition is broken into a hemisphere, and an electron microscope of its fracture surface It can be obtained from the image by image analysis.

  In the particulate composition of the present invention, the number of domains of the oil component (A) containing the reduced coenzyme Q10 dispersed in a matrix containing a water-soluble excipient as a main component and water-soluble ascorbic acids. Is more preferably, for example, preferably 5 or more domains are polydispersed, more preferably 1000 or more domains are polydispersed, more preferably 10,000 or more More preferably, the domains are polydispersed. The upper limit is not particularly limited, but is usually about 1 billion. When the number of domains in the matrix composed of the water-soluble excipient is less than 5, the content of reduced coenzyme Q10 in the finally obtained powdery composition is reduced, and a predetermined amount of reduction is achieved. When orally administering type coenzyme Q10, it is necessary to ingest a large amount of particulate composition.

  In the particulate composition of the present invention, the sphericity is preferably higher. Specifically, it is preferably 0.8 or more, more preferably 0.85 or more, and 0.9 or more. Most preferred. The higher the sphericity of the particulate composition, the smaller the total surface area per unit weight of the particulate composition, and the less the oxidation reaction caused by oxygen molecules in the air estimated to proceed from the particle surface. Tend to be. On the other hand, when the sphericity of the particulate composition is low, the total surface area per unit weight of the particulate composition increases, and oxygen in the air is estimated to travel from the surface of the particulate composition. It tends to be susceptible to oxidation reaction by molecules, and it tends to be difficult to obtain a particulate composition having high oxygen stability, which is one of the objects of the present invention.

  That is, even in the case of a particulate composition containing reduced coenzyme Q10 having the same composition, the oxidization stability of reduced coenzyme Q10 having high oxygen stability in the particulate composition is greatly affected by the sphericity. Affect. In addition, this preferable sphericity can be easily achieved by adopting a preferable production method (1) described later.

  In addition, the sphericity of the particulate composition is measured by taking an image of the target particulate composition with an electron microscope or the like, and using the image analysis software WinROOF Ver. 3.30 or the like can be used to obtain the diameter ratio of the circle having the same area and the diameter of the smallest circle that circumscribes the circle.

  Furthermore, in the particulate composition of the present invention, when the particle diameter is about the same, the smaller the surface roughness (Ra), the better. The smaller the surface roughness (Ra) of the particulate composition, the smaller the total surface area per unit weight of the particulate composition, and the corresponding amount of oxidation by oxygen molecules in the air estimated to proceed from the particle surface. It is thought that it becomes difficult to receive a reaction. On the other hand, when the surface roughness (Ra) of the particulate composition is large, the total surface area per unit weight of the particulate composition increases, and the air is estimated to advance from the particle surface by that amount. It is considered that it tends to be difficult to obtain a particulate composition having high oxygen stability, which is one of the objects of the present invention.

  The surface roughness (Ra) of the particles can be obtained as an arithmetic average surface roughness (Ra) defined by, for example, JIS B 0601-1994. The surface roughness referred to here is considered to have a substantially contradictory relationship with the sphericity, and the higher the sphericity, the smaller the surface roughness tends to be.

  In the particulate composition of the present invention, the reduced coenzyme Q10 in the composition is 10% by weight or more, preferably 20% by weight or more, more preferably 50% by weight or more, and further preferably 70% by weight or more. Preferably, 80% by weight or more is preferably not in a crystalline state, that is, in an amorphous state or in a melt state, and the proportion of the reduced coenzyme Q10 in the amorphous state or molten state in the particulate composition is higher. Is more preferable. Needless to say, it is most preferable that 100% of the reduced coenzyme Q10 in the composition, that is, the total amount is not in a crystalline state, that is, in an amorphous state or a melt state.

  Usually, the reduced coenzyme Q gradually changes to a crystalline state when stored below the melting point. However, in the particulate composition obtained by the preferred production method described below, for example, after production, 25 ° C., air Even after storage for 30 days, 10% by weight or more of the reduced coenzyme Q10 in the composition is not in a crystalline state. Since the reduced coenzyme Q10 is held in the particulate composition in an amorphous state or a melted state, not in a crystalline state, the particulate composition is disintegrated and released in the gastric fluid or intestinal fluid after oral administration. It is presumed that the reduced coenzyme Q10 in the oily component (A) also maintains the amorphous state or the melt state.

  Usually, the reduced coenzyme Q10 in an amorphous state or in a melt state is more coexisting in the living body or in the particulate composition in the stomach or intestine than the reduced coenzyme Q10 in the crystalline state. As a result, the reduced coenzyme Q10 in an amorphous state or in a melt state is more easily absorbed from the digestive tract than the reduced coenzyme Q10 in the crystalline state, and as a result, The preferred particulate composition of the present invention is considered to have high oral absorption, which is one of its purposes.

  In the particulate composition of the present invention, the structure of the oily component (A) containing the reduced coenzyme Q10 is controlled so as to form a polydisperse in a water-soluble excipient matrix. For example, in a preferable production method described later, since the oily component (A) containing the reduced coenzyme Q10 in a melt state is confined in a microcapsule surrounded by a water-soluble excipient, It is presumed that the generation probability of the crystal nucleus of the enzyme Q10 is greatly reduced and the amorphous state or the melt state is maintained for a long time after the particles are formed. That is, the structure in which the oily component (A) containing reduced coenzyme Q10 forms a domain and is polydispersed in the matrix composed of a water-soluble excipient, which is the particulate composition of the present invention. Therefore, it is considered extremely important for the purpose of realizing high oral absorbability.

  The volume average particle diameter of the particulate composition of the present invention is not particularly limited as long as the object of the present invention can be achieved, but is usually 1 μm or more, preferably 5 μm or more, more preferably 10 μm from the viewpoint of easy collection as a powder. Above, more preferably 20 μm or more, particularly preferably 30 μm or more, particularly preferably 50 μm or more. The upper limit of the volume average particle diameter is not particularly limited as long as the high stability and high absorbency of the reduced coenzyme Q10 targeted by the present invention can be maintained, but it can be processed into foods, pharmaceuticals, cosmetics and the like. In view of ease, it is usually 5000 μm or less, preferably 3000 μm or less, more preferably 2000 μm or less, further preferably 1000 μm or less, particularly preferably 800 μm or less, and particularly preferably 700 μm or less.

  That is, the volume average particle size of the particulate composition of the present invention is usually 1 to 5000 μm, preferably 5 to 3000 μm, more preferably 10 to 2000 μm, still more preferably 20 to 1000 μm, particularly preferably 30 to 800 μm, especially Preferably it is 50-700 micrometers. The volume average particle diameter can be measured using, for example, an ethanol solvent or the like in a laser diffraction / scattering type particle size distribution measuring apparatus (Nikkiso Co., Ltd .; Microtrack MT3000II, manufactured by Horiba, Ltd .; LA-950, etc.). .

  In the particulate composition of the present invention, the true specific gravity of the water-soluble excipient component that is the main component of the matrix is preferably 1.25 or more, more preferably 1.27 or more. Most preferably, it is 30 or more. The true specific gravity of the water-soluble excipient varies depending on the water content, but the standard only has to be satisfied under normal handling conditions or under a condition where the water content is 3% by weight or less. As the true specific gravity of the water-soluble excipient is higher, the matrix in the particulate composition forms a dense packing state, thereby providing longer-term stability of the reduced coenzyme Q10 in the domain. realizable.

  The method for obtaining such a true specific gravity value is not particularly limited, but can be achieved by adopting the production method of the present invention described later. In particular, gum arabic that is not in a gel state is used as a water-soluble excipient component. When used, a particularly high true specific gravity value can be obtained. On the other hand, in a particulate composition obtained by using gelatin or the like as a water-soluble excipient component and obtained by a spray cooler method or a liquid curing method, the true specific gravity of the water-soluble excipient is generally low.

  The upper limit of the true specific gravity of the water-soluble excipient component is not particularly limited as long as the object of the present invention can be achieved, but is practically about 1.50 or less.

  The true specific gravity can be measured by a known measuring method such as a liquid phase substitution method or a gas phase substitution method. The true specific gravity of the water-soluble excipient can be converted from the density of the oily component (A) contained in the particulate composition and the content (% by weight) by calculation.

  In the present invention, the true specific gravity of the entire particulate composition is not particularly limited because it is affected by the content of reduced coenzyme Q10 and water-soluble excipient in the particulate composition. When enzyme Q10 is contained in the particulate composition in an amount of about 15 to 30% by weight, it is usually 1.1 or more, preferably 1.2 or more.

  In addition, various additives that can be used for various purposes and active ingredients other than coenzyme Q are added to the particulate composition of the present invention in accordance with each purpose. Can do.

  For example, in addition to the above compounds, excipients such as crystalline cellulose, calcium phosphate and calcium sulfate, calcium citrate, calcium carbonate, sodium bicarbonate, crystalline cellulose, carboxymethylcellulose, tragacanth, alginic acid and other disintegrants, talc, stearic acid Lubricants such as magnesium, polyethylene glycol, silica, hydrogenated oil, titanium oxide, food dyes, bengara dyes, safflower dyes, caramel dyes, gardenia dyes, tar dyes, chlorophyll dyes, stearic acid, talc, light anhydrous silicic acid , Aggregation inhibitors such as hydrous silicic acid dioxide, higher alcohols, absorption accelerators such as higher fatty acids, solubilizing aids such as fumaric acid, succinic acid, malic acid, benzoic acid, sodium benzoate, ethyl paraoxybenzoate, List stabilizers such as beeswax That.

  In addition, the active ingredient other than coenzyme Q is not particularly limited as long as it is acceptable for food, cosmetics, or pharmaceutical use. For example, glutathione, L-cysteine, N-acetylcysteine, reduced α-lipoic acid, Tocotrienol, vitamin E (α-tocopherol) and its ester derivatives, erythorbic acid and its ester derivatives and salts, vitamin A and its ester derivatives, carotenoid, rutin, zeaxanthin, astaxanthin, lycopene, flavonoid, L-carnitine and its tartrate Extracted from pharmacologically acceptable salts such as fumarate, acetyl-L-carnitine, propionyl-L-carnitine, magnesium, zinc, selenium, manganese, riboflavin, niacinamide, curcuminoid, grape seed and pine bark Proan Highly unsaturated fatty acids obtained by concentrating from tocianidine, NADH (reduced nicotinamide adenine dinucleotide), NADPH (reduced nicotinamide adenine dinucleotide phosphate), resveratrol, moss peach extract, milk thistle extract, fish oil, etc. Can be mentioned.

  Preferably, glutathione, L-cysteine, tocotrienol, vitamin E (α-tocopherol) and its ester derivatives, erythorbic acid and its ester derivatives and salts, vitamin A and its ester derivatives, carotenoids, rutin, astaxanthin, lycopene, flavonoids, L -Carnitine and the like. Among these, from the viewpoint of the stability of reduced coenzyme Q10, it is preferable to use an active ingredient having an antioxidative action such as carotenoid, astaxanthin, vitamin E and its ester derivative.

  Needless to say, the various components listed here can be used as a mixture of two or more. These various additives and active ingredients are preferably contained in a matrix containing a water-soluble excipient as a main component if water-soluble, or in an oily component (A) that becomes a domain if fat-soluble. It is not limited to it.

  In general, fat-soluble oxidizable active ingredients stabilized by microencapsulation with water-soluble excipients have oxidative stability under conditions where water-soluble excipients absorb moisture, such as in humid conditions. Although there is a tendency to decrease (Y. Minemoto, et al., Food Sci. Technol. Res., 7, 91-93, 2001), in the particulate composition of the present invention, moisture is contained in the particulate composition. Even when contained, high oxidative stability of the reduced coenzyme Q10 can be realized. Accordingly, the water content in the particulate composition of the present invention is not particularly limited, and can contain, for example, about 0.01 to 30% by weight of water. The water content in the particulate composition of the present invention is preferably 0.01 to 20% by weight, more preferably 0.01 to 15% by weight. When the water content in the particulate composition in the present invention is more than 30% by weight, it tends to be difficult to obtain a significant effect of improving oxidative stability, but the target oxidative stability can be achieved. This is not the case. On the other hand, the lower limit of the water content in the particulate composition is preferably smaller in view of the oxidation stability of the reduced coenzyme Q10, but is usually 0.01% by weight or more.

As described above, conventionally, in order to improve the oxidation stability of reduced coenzyme Q10,
1) Fat-soluble oxidized and / or reduced coenzyme Q10 is dissolved as homogeneously as possible in an oil-based component consisting of fat-soluble ascorbic acids, fats and oils, and / or a surfactant, and if necessary a fat-soluble solvent, Fat-soluble oxidized coenzyme Q10 and / or reduced coenzyme Q10 and a fat-soluble reducing agent are combined at the molecular level,
2) A large amount of a solvent (for example, ethanol) having a property of dissolving both oxidized coenzyme Q10 and / or reduced coenzyme Q10 and reducing agent is used, and oxidized coenzyme Q10 and / or reduced at the molecular level. Dissolving type coenzyme Q10 and reducing agent,
However, in the particulate composition of the present invention, by adding a water-soluble ascorbic acid to a matrix mainly composed of a water-soluble excipient, a solvent such as an oil or fat, an emulsifier or ethanol is used. In spite of the fact that there is no component to be present or that the reduced coenzyme Q10 and ascorbic acids are completely incompatible with each other at the molecular level, the oxidation of reduced coenzyme Q10 It has been found that the stability can be greatly improved. That is, even in a situation where the entire system is not compatible at the molecular level, the oxidation stability of the reduced coenzyme Q10 can be greatly improved. It has been found for the first time that it can be maintained even when moisture is absorbed.

  In the particulate composition of the present invention, the retention rate (%) of reduced coenzyme Q10 after storage for 30 days under light shielding conditions at 40 ° C. in air (sealed or open system) (initial reduced coenzyme) The ratio of Q10 to the weight is preferably 80% by weight or more, more preferably 85% by weight or more, further preferably 90% by weight or more, and particularly preferably 95% by weight or more. . The humidity in the storage atmosphere is not particularly limited, but is usually about 90% or less relative humidity, preferably about 75% or less, more preferably about 60% or less, and particularly preferably about 40% or less relative humidity. . However, as described above, the particulate composition of the present invention in which water-soluble ascorbic acids are contained in the matrix is less affected by the water content on the oxidative stability than when no water-soluble ascorbic acids are contained. Therefore, even when the humidity in the storage atmosphere is high and the water content is increased due to moisture absorption, the reduced coenzyme Q10 can be held more stably.

  Furthermore, in the particulate composition of the present invention, when the particulate composition is collapsed, the reduced coenzyme Q10 is released in a fine state that is effective for absorption into the digestive tract. It becomes good.

  Next, the preferable manufacturing method of the particulate composition containing reduced coenzyme Q10 of this invention is demonstrated. The particulate composition of the present invention is preferably obtained by the following production method, but the production method is not limited to the following if a similar particulate composition can be obtained by another production method.

The particulate composition containing the reduced coenzyme Q10 of the present invention is preferably
(1) An oil-in-water emulsion composition prepared from an aqueous solution containing water-soluble ascorbic acids and a water-soluble excipient and an oily component (a) containing coenzyme Q10 is suspended in the oily component (B). After removing the water in the oil-in-water emulsion composition in the oil component (B) (hereinafter referred to as production method (1)), or
(2) A method in which an oil-in-water emulsion composition prepared from an aqueous solution containing water-soluble ascorbic acids and a water-soluble excipient and an oily component (a) containing coenzyme Q10 is spray-dried in a gas phase ( Hereinafter, it can be produced by the production method (2)).

  In the above production methods (1) and (2), an aqueous solution (hereinafter referred to as “excipient aqueous solution”) that is an aqueous phase of the oil-in-water emulsion composition is prepared by using water-soluble ascorbic acid and water-soluble excipient in water. It is preferably used in the form of a dissolved aqueous solution, and the concentration thereof is not particularly limited, but the aqueous solution has a viscosity that does not exceed 10 poise, preferably 5 poise, more preferably 2 poise, and still more preferably 1 poise. It is preferable to handle it from the viewpoint of ensuring liquid transfer properties. Specific examples and preferred examples of the water-soluble ascorbic acids and the water-soluble excipient at this time are the same as those described in the description of the particulate composition.

  The amount of the water-soluble ascorbic acid used in the production methods (1) and (2) of the present invention is an amount effective for improving the oxidative stability of the reduced coenzyme Q10 in the resulting particulate composition. Although not particularly limited, for the purpose of sufficiently improving the stability of the reduced coenzyme Q10 in the obtained particulate composition, water-solubility with respect to 100 parts by weight of coenzyme Q10 used for the oily component (a) The amount of ascorbic acid used is preferably 1 part by weight or more, more preferably 2 parts by weight or more, still more preferably 5 parts by weight or more, and particularly preferably 10 parts by weight or more. In addition, when reducing the oxidized coenzyme Q10 contained in the oily component (a) in the production process, in addition to the amount necessary for improving the stability, the amount necessary for reducing the oxidized coenzyme Q10. It is preferable to use water-soluble ascorbic acid.

  In this case, the amount of water-soluble ascorbic acid used varies depending on the ratio of oxidized coenzyme Q10 contained in coenzyme Q10 to be used. For example, when all of coenzyme Q10 used is oxidized coenzyme Q10, The amount of water-soluble ascorbic acid used relative to 100 parts by weight of coenzyme Q10 used in the oil component (a) is preferably 20 parts by weight or more, more preferably 30 parts by weight or more, even more preferably 40 parts by weight or more, particularly Preferably it is 50 weight part or more.

  On the other hand, the upper limit of the content of the water-soluble ascorbic acids used in the production method of the present invention is not particularly limited in achieving the object of the present invention, but from the viewpoint of economy, the oil component (a) The amount is preferably 500 parts by weight or less, more preferably 300 parts by weight or more, still more preferably 250 parts by weight or less, and particularly preferably 200 parts by weight or less with respect to 100 parts by weight of the coenzyme Q10 used.

  That is, the amount of water-soluble ascorbic acids used is preferably 1 to 500 parts by weight, more preferably 2 to 300 parts by weight, based on 100 parts by weight of coenzyme Q10 used for the oil component (a). 5 to 250 parts by weight is more preferable, and 10 to 200 parts by weight is particularly preferable. In addition, when reducing a considerable amount of oxidized coenzyme Q10 contained in the oil component (a) in the production process, use of water-soluble ascorbic acids for 100 parts by weight of the coenzyme Q10 used in the oil component (a) The amount is preferably 20 to 500 parts by weight, more preferably 30 to 300 parts by weight, even more preferably 40 to 250 parts by weight, and particularly preferably 50 to 200 parts by weight.

  In the above production methods (1) and (2), the oil component (a) containing coenzyme Q10 may be prepared by adding oil or fat and / or interface to coenzyme Q10 melted at 50 ° C. or higher as necessary. The method of adding the activator (D) and the like and mixing by stirring or the like is the simplest and preferable, but is not limited thereto. The coenzyme Q10 used for the oil component (a) at this time is not only reduced coenzyme Q10, a mixture of reduced coenzyme Q10 and oxidized coenzyme Q10, but also oxidized coenzyme Q10 alone. It can also be used.

  In the production method of the present invention, as described later, when oxidized coenzyme Q10 is used alone or when coenzyme Q10 having a low content of reduced coenzyme Q10 is used, oxidized form is used in the production process. By reducing the coenzyme Q10, the reduced coenzyme Q10 ratio in the resulting particulate composition can be increased. Specific examples and preferred examples of the other components of the oil component (a), such as oils and surfactants (D), and the composition ratio of the oil component (a), etc., are the oil properties described in the description of the particulate composition. Same as component (A).

  Next, in the production methods (1) and (2) of the present invention, an oil-in-water emulsion composition is prepared from the oil component (a) containing the coenzyme Q10 and an aqueous excipient solution. Examples of the method for preparing the oil-in-water emulsion composition include coenzyme Q10 prepared at a temperature equal to or higher than the melting point of coenzyme Q10 in the aqueous excipient solution previously heated to 50 ° C. or higher. It is most convenient to add the oil component (a) to be added and finely disperse and emulsify the oil component (a) to a desired average particle size using a known emulsifier such as a high-pressure homogenizer. preferable. In addition to this, coenzyme Q10 powder and, if necessary, other oil components are added to an aqueous excipient solution that has been heated to 50 ° C. or higher in advance, and coenzyme Q10 and Other oily components are melted and then emulsified, or coenzyme Q10 is added as a powder and / or melted at 50 ° C. or higher to an aqueous solution containing a water-soluble excipient, necessary Depending on the case, after adding other oily components, the mixture may be heated to 50 ° C. or higher, and coenzyme Q10 and other oily components may be melted and emulsified, but is not limited thereto.

  In the production method of the present invention, the preferred emulsified particle diameter of the oil component (a) of the oil-in-water emulsion composition is not particularly limited, but the average particle diameter of the oil component (a) of the oil-in-water emulsion composition is large. In some cases, the absorbability of reduced coenzyme Q10 in the resulting particulate composition may decrease, and is usually 50 μm or less, preferably 20 μm or less, more preferably 15 μm or less, and particularly preferably 10 μm. It is as follows. On the other hand, when the average particle size of the oil component (a) of the oil-in-water emulsion composition is small, an excess of a water-soluble excipient is required to maintain the stability of the emulsified droplets in the production process. Since problems such as requiring an excessive load on the emulsifying device occur, it is usually 0.001 μm or more, more preferably 0.05 μm or more, and particularly preferably 0.01 μm or more.

  Since the emulsion particle size of the oil component (a) of the oil-in-water emulsion composition and the domain particle size of the oil component (A) in the resulting particulate composition are correlated, the particle size of the emulsion droplets in this step By controlling, the domain particle diameter in the obtained particulate composition can be controlled.

  The emulsion particle diameter of the oil component (a) of the oil-in-water emulsion composition can be measured by a commercially available dynamic light scattering particle size distribution measuring device or a laser diffraction / scattering particle size distribution measuring device.

  In the production methods (1) and (2) of the present invention, the step of preparing the oil-in-water emulsion composition from the oily component (a) and the aqueous excipient solution, and the temperature in the emulsification step are the oil-in-water composition. The temperature is not particularly limited as long as it is at or above the temperature at which the coenzyme Q10 is melted, but is usually 50 ° C or higher, preferably 55 ° C or higher, more preferably 60 ° C or higher. The upper limit is the boiling point of the system and differs depending on the conditions such as pressurization, and the temperature cannot be defined unconditionally. However, in the case of normal pressure conditions, it is usually 100 ° C. or lower, preferably 90 ° C. or lower.

  In the production method (1) of the present invention, the above oil-in-water emulsion composition is further mixed with another oil component (B), and an oil-in-water component is added to the oil component (B) so as to obtain a desired particle size. The type emulsion composition is suspended to obtain an O / W / O type emulsion. In the above mixing operation, for example, it is most convenient and preferable to add the oil-in-water emulsion composition containing coenzyme Q10 to the oil component (B) that has been heated to 50 ° C. or higher in advance. However, the present invention is not limited to this. Adjustment of the suspended particle size of the oil-in-water emulsion composition in the oil component (B) can be achieved by imparting shear to the mixed solution, such as stirring and liquid circulation. The temperature of the oil component (B) at the time of preparing the mixed liquid is usually preferably in the range of 50 to 120 ° C. in order to avoid rapid evaporation of moisture.

  Although there is no restriction | limiting in particular in the mixing ratio of the oil-in-water-type emulsion composition and oil-based component (B) in the manufacturing method (1) of this invention, The liquid mixture of an oil-in-water-type emulsion composition and oil-based component (B) The weight percent of the oil-in-water emulsion composition is preferably 1% by weight or more, more preferably 10% by weight or more, and particularly preferably 15% by weight or more from the viewpoint of production efficiency. preferable. Further, from the viewpoint of suspendability in the oil component (B) of the oil-in-water emulsion composition, it is preferably 70% by weight or less, particularly preferably 60% by weight or less, and 50% by weight or less. Is particularly preferred. Usually, it can be suitably carried out at 1 to 70% by weight, preferably 10 to 60% by weight, more preferably 15 to 50% by weight. When the oil-in-water emulsion composition in the mixed liquid of the oil-in-water emulsion composition and the oil component (B) is less than 1% by weight, production efficiency is lowered, which is not preferable. When the oil-in-water emulsion composition in the mixed liquid of the oil-in-water emulsion composition and the oil component (B) is 70% by weight or more, the oil-in-water emulsion composition is suspended in the oil component (B). This tends to be difficult.

  In the production method (1) of the present invention, the water is removed from the oil-in-water emulsion composition suspended in the oil component (B) after the O / W / O emulsion is formed. As a method for removing water from the oil-in-water emulsion composition, for example, the water is evaporated by heating to 80 ° C. or higher, preferably 100 ° C. or higher under atmospheric pressure, or under any pressure under reduced pressure. However, the method is not limited to these, for example, a method of evaporating moisture by setting the temperature to be near the boiling point of water in From the viewpoint of minimizing the operation time, it is preferable to carry out under an arbitrary reduced pressure.

  In this invention, the oil-based component (B) in a manufacturing method (1) is a component containing fats and oils and surfactant (E) as needed. The oil component (B) is not particularly limited as long as it can suspend the oil-in-water emulsion composition, and may be, for example, natural fats and oils from animals and plants, such as synthetic fats and processed fats and oils. May be. More preferably, it is acceptable for food, cosmetics or medicine. For example, as vegetable oils and fats, for example, palm 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, sesame oil, Examples include cottonseed oil, sunflower seed oil, kapok oil, evening primrose oil, shea fat, monkey fat, cacao fat, sesame oil, safflower oil, olive oil, etc. Examples of animal fats include pork fat, milk fat, fish oil, beef tallow Furthermore, the fats and oils (for example, hardened oil) which processed these by fractionation, hydrogenation, transesterification, etc. can also be mentioned. Needless to say, medium chain fatty acid triglycerides (MCT) may also be used. Moreover, you may use these mixtures.

  Examples of the medium-chain fatty acid triglyceride include triglycerides in which the fatty acid has 6 to 12 carbon atoms, preferably 8 to 12 carbon atoms.

  Of the above oils and fats, vegetable oils, synthetic oils and processed oils and fats are preferable from the viewpoint of ease of handling and odor. For example, palm oil, palm oil, palm kernel oil, rapeseed oil, rice oil, soybean oil, cottonseed oil, safflower oil, olive oil, MCT and the like.

  In the production method (1) of the present invention, the oil component (B) may be an oil or fat alone, but for the purpose of ensuring the dispersion stability of the oil-in-water emulsion composition droplets dispersed in the oil component (B). If necessary, the surfactant (E) can be added to the oil component (B). The droplets of the oil-in-water emulsified composition gradually increase in tackiness as drying progresses, and tend to aggregate between particles. However, when the surfactant (E) is allowed to coexist in the oil component (B), the aggregation between the oil-in-water emulsion composition droplets during drying with increased tackiness is greatly relieved, and as a result, The recovery rate of the particulate composition having a desired volume average particle diameter can be remarkably improved, which is preferable.

  Although there is no restriction | limiting in particular in content of surfactant (E) in oil-based component (B), From viewpoints, such as aggregation suppression between the droplets of the oil-in-water emulsion composition in the middle of drying, oil-based component (B) The weight percent of the surfactant (E) is usually 0.001 wt% or more, preferably 0.005 wt% or more, and more preferably 0.01 wt% or more. Although the upper limit is not particularly limited, it is usually 95% by weight or less, preferably 80% by weight or less, more preferably 60% by weight or less, from the viewpoint of fluidity of the oil component (B), removability of the surfactant (E), and the like. It is.

  The surfactant (E) is not particularly limited as long as it is acceptable for food, cosmetics, and pharmaceutical use, but is particularly preferably acceptable for food, for example, glycerin fatty acid esters having an HLB of 10 or less, Examples include surfactants such as polyglycerin esters, sucrose fatty acid esters, sorbitan fatty acid esters, polyoxyethylene sorbitan fatty acid esters, and lecithins. Needless to say, in the present invention, these can be used alone or as a mixture of two or more.

  Examples of glycerin fatty acid esters include monoglycerides and diglycerides in which the fatty acid has 6 to 22 carbon atoms, preferably 6 to 18 carbon atoms.

  Examples of the polyglycerin esters include polyglycerin mainly composed of polyglycerin having a polymerization degree of 2 to 10, and one or more hydroxyl groups of polyglycerin each having 6 to 22, preferably 6 to 18 carbon atoms. What esterified fatty acid is mentioned.

Examples of sucrose fatty acid esters include those obtained by esterifying a fatty acid having 6 to 22 carbon atoms, preferably 6 to 18 carbon atoms, to one or more hydroxyl groups of sucrose. One or more hydroxyl groups may be esterified with a fatty acid having 6 to 22, preferably 6 to 18 carbon atoms.

  As the polyoxyethylene sorbitan fatty acid esters, one or more hydroxyl groups of sorbitans are substituted with polyoxyethylene chains, and one or more of the existing hydroxyl groups each have 6 to 18 carbon atoms, preferably May be those esterified with 6-18 fatty acids.

  Examples of lecithin include egg yolk lecithin, purified soybean lecithin, phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, sphingomyelin, dicetylphosphate, stearylamine, phosphatidylglycerol, phosphatidic acid, phosphatidylinositolamine, cardiolipin, ceramide phosphorylethanolamine, ceramide Examples include phosphorylglycerol, enzymatically decomposed lecithin (lysolecithin), and mixtures thereof.

  The HLB of the surfactant (E) is preferably 10 or less, more preferably 7 or less, from the viewpoint of efficiently suppressing aggregation between the oil-in-water emulsion composition droplets during drying. Preferably, it is most preferably 5 or less. However, lecithins are not limited to the HLB and can be preferably used.

  Among the above surfactants (E), in the production method (1) of the present invention, specifically, the aggregation between the oil-in-water emulsion composition droplets during drying can be efficiently suppressed, and specifically, Mono, such as glycerol monostearate, monoglycerol monooleate, monoglycerol monomyristate, monoglycerol monocaprylate, monoglycerol monolaurate, monoglycerol monobehenate, monoglycerol monoerucate Glycerin monofatty acid ester; monoglycerin distearate, monoglycerin dioleate, monoglycerin dicaprylate, monoglycerin dilaurate, etc .; monoglycerin stearate citrate ester Monoglycerin stearic acid acetate, monoglycerin palm hardened oil acetic acid ester, monoglycerin stearic acid succinic acid ester, monoglycerin caprylic acid succinic acid ester, monoglycerin stearic acid lactate, monoglyceryl stearate diacetyl tartaric acid ester, etc. Fatty acid organic acid ester: Monoglycerin beef tallow fatty acid ester, monoglycerin rapeseed hardened oil fatty acid ester, monoglycerin soybean hardened oil fatty acid ester, monoglycerin cottonseed oil fatty acid ester, monoglycerin safflower oil fatty acid ester, etc. Monoglycerol fatty acid ester obtained; polyglycerol fatty acid ester such as ester of polyglycerol having an average degree of polymerization of 2 to 10 and fatty acid having 6 to 22 carbon atoms, and average Glycerin fatty acid esters such as polyglycerin condensed ricinoleic acid ester such as ester of polyglycerin having a degree of synthesis of 2 to 10 and polyricinoleic acid having a degree of condensation of 2 to 4; propylene glycol monostearate, propylene glycol monooleate, and Propylene glycol fatty acid esters such as propylene glycol monolaurate; sorbitan fatty acid esters such as sorbitan distearate, sorbitan tristearate, sorbitan sesquioleate, sorbitan dioleate, and sorbitan trioleate; poly Polyoxyethylene sorbitan such as oxyethylene sorbitan monostearate and polyoxyethylene sorbitan monooleate Tan fatty acid esters; and one or a mixture of two or more selected from lecithins such as soybean lecithin, egg yolk lecithin, and enzymatically decomposed lecithin. Among them, preferably glycerol fatty acid esters and / or one or a mixture of two or more selected from lecithins such as soybean lecithin, egg yolk lecithin, and enzymatically decomposed lecithin, more preferably monoglycerol monofatty acid ester and monoglycerol diester. Fatty acid ester, monoglycerin fatty acid organic acid ester (especially monoglycerin fatty acid acetate, monoglycerin coconut palm oil acetate), polyglycerin fatty acid ester (especially polyglycerin having an average polymerization degree of 2 to 10 and 6 to 22 carbon atoms, preferably 6-18 fatty acid esters), and polyglycerin condensed ricinoleic acid esters (especially esters of polyglycerin having an average polymerization degree of 2 to 10 and polyricinoleic acid having a condensation degree of 2 to 4), soybean lecithin, egg yolk lecithin, Selected from enzymatically degraded lecithin 1 or a mixture of two or more thereof, more preferably monoglycerin fatty acid organic acid esters (particularly monoglycerin fatty acid acetate, monoglycerin coconut palm oil acetate), and specific examples of monoglycerin monostearate Examples thereof include 50% acetylated product, fully acetylated product of coconut oil monoglyceride, soybean lecithin, egg yolk lecithin, and one or a mixture of two or more of enzymatically degraded lecithin.

  In the production method (1) of the present invention, it is particularly preferable to use MCT as the fat and oil, and egg yolk lecithin, soybean lecithin or enzymatically decomposed lecithin as the surfactant (E) in combination.

  In the production method (1) of the present invention, the time required for removing moisture from the oil-in-water emulsion composition droplets is not particularly limited, but is preferably 1 second to 24 hours, more preferably 3 seconds to 12 hours, Most preferably, it is in the range of 5 seconds to 6 hours. When the time required for removing moisture is less than 1 second, intense foaming may occur due to evaporation of moisture from the oil component (B) at once. On the other hand, when the time required for removing moisture is longer than 24 hours, productivity is lowered.

  Incidentally, the removal of water in the production method (1) of the present invention means that even when the water is not completely removed, the drying of the oil-in-water emulsion composition droplets proceeds and the particles are recovered in the form of particles. As long as the state is possible. The water content of the particulate composition is usually preferably 30% by weight or less, more preferably 20% by weight or less, and most preferably 15% by weight or less of the weight of the particles after recovery. Needless to say, the lower limit is 0% by weight, but it is usually 0.01% by weight or more.

  In the production method (1), the method for recovering the particulate composition after removing the water is not particularly limited, but after removing the oil component (B) by solid-liquid separation, the obtained particle composition is removed with an organic solvent or the like. It is most convenient and preferred to wash and remove most of the oil component (B), and further to remove the organic solvent by drying and recover it as a powder.

  The organic solvent for washing the oil component (B) is not particularly limited as long as it is an organic solvent that can dissolve and remove the oil component (B), but it can be used for the production of foods, pharmaceuticals, cosmetics and the like. Is preferred. Examples of such a solvent include, but are not limited to, ethanol, methanol, isopropanol, acetone, hexane, ethyl acetate, tetrahydrofuran, and the like. Among these, when using the particulate composition of the present invention for food applications, it is most preferable to use ethanol. Examples of the method for drying the organic solvent include, but are not limited to, vacuum drying, heat drying, and air drying. In addition, classification operation can also be implemented in order to arrange | position the particulate composition after collection | recovery to a particle diameter desirable as a predetermined | prescribed product.

  On the other hand, in the production method (2) of the present invention, as described above, an oil-in-water emulsion composition is prepared from the oil component (a) containing coenzyme Q10 and an aqueous excipient solution, and the oil-in-water emulsion is prepared. The composition can be made into the particulate composition of the present invention by spray drying in the gas phase. A so-called spray drying method can be used as the spray drying method in the gas phase. The conditions for spray drying can be appropriately selected from the conditions that are usually carried out.

  Of the two types of production methods described above, in production method (1), the individual oil-in-water emulsion composition liquid droplets suspended substantially spherically in the oil component (B) retained a spherical shape. Since moisture removal proceeds in a state, it tends to be easy to obtain a particulate composition having high oxidation stability, high sphericity and small surface roughness (Ra), which is the object of the present invention. This is a preferred production method.

  On the other hand, in the production method (2), particles containing reduced coenzyme Q10 having a nearly spherical shape and a small surface roughness (Ra) can be obtained by appropriately controlling the temperature and residence time during drying. A composition can be produced.

  In addition, about manufacturing method (1) and (2) in this invention, of course, in order to suppress the oxidation of reduced coenzyme Q10 in a manufacturing process, each operation can be implemented in a deoxygenated atmosphere.

  In addition, in the production methods (1) and (2) of the present invention, when coenzyme Q10 containing oxidized coenzyme Q10 or oxidized coenzyme Q10 itself is used as a production raw material, By reducing with water-soluble ascorbic acid using at least a part of oxidized coenzyme Q10, the ratio of reduced coenzyme Q10 in the resulting particulate composition can be increased. Examples of the production process in which oxidized coenzyme Q10 is reduced to water-soluble ascorbic acids include a process for preparing the above-described oil-in-water emulsion composition, a process for removing water from the oil-in-water emulsion composition, and the like. However, even in this case, the coenzyme used as a raw material is easy to control the content of reduced coenzyme Q10 in the particulate composition obtained (or the weight ratio of reduced coenzyme Q10 to coenzyme Q10). A higher weight ratio of reduced coenzyme Q10 in Q10 is preferred.

  Next, a method for stabilizing the particulate composition containing the reduced coenzyme Q10 of the present invention described above will be described.

  The stabilization described in the present specification indicates that reduced coenzyme Q10 is inhibited from being oxidized to oxidized coenzyme Q10. The stabilization method in the present invention can also be rephrased as a method for stably handling a particulate composition containing reduced coenzyme Q10 against oxidation. The term “handling” as used herein refers to maintaining or exerting the function of an object by applying an external action to the object. Examples of handling can include, but are not limited to, dispensing from a coating machine, packaging, packing, storage, storage, and transport. Storage is preferred.

  The upper limit of the temperature in the handling environment in the method for stabilizing a particulate composition containing reduced coenzyme Q10 of the present invention is usually about 100 ° C. or lower, preferably about 80 ° C. or lower, more preferably about 60 ° C. or lower. More preferably, it can be carried out at about 40 ° C. or less, particularly preferably at about 20 ° C. or less. In this case, the lower limit of the temperature is usually about −100 ° C. or higher, preferably about −80 ° C. or higher, more preferably about −60 ° C. or higher, further preferably about −40 ° C. or higher, particularly preferably −20 ° C. or higher. .

  In the present invention, the particulate composition containing reduced coenzyme Q10 and the preparation containing the composition can be further stabilized by adjusting the relative humidity in the handling environment.

  The particulate composition of the present invention containing water-soluble ascorbic acids in a matrix mainly composed of a water-soluble excipient of the present invention is more easily handled in comparison with a particulate composition not using water-soluble ascorbic acids. The effect of humidity can be dramatically reduced. However, in consideration of long-term storage stability, the atmospheric condition under the handling environment is preferably lower humidity, and is usually about 90% or less, preferably about 80% or less, more preferably about relative humidity. The particulate composition containing the reduced coenzyme Q10 of the present invention can be handled more stably in an environment adjusted to about 70% or less, particularly preferably relative humidity of about 60% or less. The lower limit of the relative humidity is 0%.

  The environment in which the relative humidity is adjusted is given by dehumidification from the environment or introduction of dehumidified gas (air or dry inert gas such as dry nitrogen) into the environment. The dehumidification is not particularly limited, but can be achieved by freezing moisture, using a dehumidifier, a desiccant (silica gel, calcium chloride, synthetic zeolite, etc.) and the like. Needless to say, the method is not particularly limited as long as an environment in which the relative humidity is adjusted is given.

  In order to maximize the effects of the present invention, the particle composition of the present invention is naturally produced and stored in a deoxygenated atmosphere from the viewpoint of the stability of the reduced coenzyme Q10. For example, it is preferable to carry out in a deoxygenated atmosphere such as an inert gas such as nitrogen gas or argon gas.

  Further, in the present invention, the reduced coenzyme Q10 in the particulate composition is lengthened by packaging and packing the particulate composition of the present invention with a glass, plastic and / or metal material. It can be stored for a stable period. The form of packaging / packaging may be either sealed (sealed) or open, but sealed packaging / packaging is preferred.

  Examples of the glass material include soft glass and hard glass. Examples of the plastic material include high density polyethylene, medium density polyethylene, low density polyethylene, polypropylene, polyethylene terephthalate, polyvinyl alcohol, polyvinyl chloride, polyvinylidene chloride, and nylon. Needless to say, films made by laminating the above plastic materials, films made by laminating aluminum etc. on plastic materials such as aluminum laminate, and films made by evaporating aluminum, alumina, silica, etc. on plastic materials are also made of plastic. Included in the material. Examples of the metal material include iron, aluminum, zinc, nickel, cobalt, copper, tin, titanium, chromium, and alloys thereof (stainless steel, brass, etc.). In addition, materials such as enamels that combine glass and metal can be used.

  The material is preferably molded into a bottle, bag, can, drum, box or the like, and the particulate composition of the present invention is packaged and packed. Moreover, it can also be set as PTP packaging, three-side seal packaging, four-side seal packaging, pillow packaging, strip packaging, aluminum molding packaging, stick packaging, etc. using said raw material. When materials with relatively low gas barrier properties and moisture-proof properties such as polyethylene are used, it is preferable to use double or more packaging / packaging. At this time, aluminum laminate, vapor deposited film of aluminum, alumina, silica, etc., glass It is particularly preferable to use a material having relatively high gas barrier properties and moisture resistance such as metal. After packaging and packing, it can be transported and stored in steel drums, resin drums, fiber drums, cardboard, etc. as necessary. At that time, a moisture-proofing agent such as silica gel, calcium chloride, or synthetic zeolite can be enclosed.

  In the stabilization method of the present invention, the retention rate (%) of the reduced coenzyme Q10 after storage for 30 days under the light-shielding condition at 40 ° C. in the air in the particulate composition containing the reduced coenzyme Q10 of the present invention ) Is not particularly limited, but is usually about 80% by weight or more, preferably about 85% by weight or more, and more preferably about 90% by weight or more.

  Then, the preferable formulation form of the particulate composition containing the reduced coenzyme Q10 of this invention is demonstrated.

  The particulate composition containing reduced coenzyme Q10 obtained in the present invention is a tablet, pill, capsule (hard capsule, soft capsule, microcapsule, etc.), chewable tablet, powder, granule, syrup, drink, etc. It can be processed or used as pharmaceuticals, other foods, cosmetics, etc. as a formulation, and a formulation form for realizing the high oxidative stability and high oral absorbability which are the objects of the present invention can be realized. In addition, the formulation here refers not only to a medicine but also to those belonging to foods and cosmetics and having the above-mentioned form. In formulation, in addition to excipients, disintegrants, lubricants, binders, anti-aggregation agents, absorption promoters, solubilizers, antioxidants, stabilizers, etc., in addition to capsules, oils and fats, lecithin, A surfactant such as lysolecithin can also be used in combination.

  For example, the particulate composition of the present invention is made into a mixed slurry suspended in the oil component (F), and the slurry is filled into a soft capsule such as gelatin, thereby providing high oxidation stability and high oral absorption. A soft capsule preparation that can be realized is also possible.

  Conventionally, as a soft capsule preparation containing reduced coenzyme Q10, a composition in which reduced coenzyme Q10 powder is dispersed or dissolved in a slurry form in an oily component mainly composed of vegetable oil and / or a surfactant is used as a soft capsule. Preparations filled in are known. However, in this preparation, the invasion of oxygen from the outside is physically shielded only by the capsule shell, and the reduced coenzyme Q10 is stabilized. Especially in storage under humid conditions, The stability of reduced coenzyme Q10 is not sufficient.

  On the other hand, in the soft capsule preparation obtained by filling the mixed slurry in which the particulate composition of the present invention is suspended in the oil component (F) into a soft capsule such as gelatin, the reduced coenzyme Q10 is only in the capsule shell. In addition, it is possible to physically shield the entry of oxygen from the outside with a double film combined with the water-soluble excipient layer, and it becomes possible to obtain a preparation with better oxidation stability. The conceptual diagram is shown in FIG.

  Since the soft capsule preparation obtained by processing the particulate composition of the present invention can be stably handled and / or stored even under humid conditions, it is particularly stable under humid conditions compared to conventional soft capsule preparations. Are better.

  As the oil component (F) used in the soft capsule preparation, waxes such as beeswax, etc., besides the above-mentioned oil and fat and surfactant (emulsifier) can be used alone or in a mixture of two or more. However, the present invention is not limited thereto, and other components may be optionally added so as to improve the oral absorbability of reduced coenzyme Q10 in the capsule, or a combination with any other active ingredient may be used. . Needless to say, among the oils and fats, surfactants and waxes, those acceptable for foods, pharmaceuticals and the like are preferable.

  Further, in the present invention, the particulate composition of the present invention is used as it is or as a powder obtained by mixing with a general formulation component such as any excipient or lubricant, or the oil component (F It is possible to obtain a hard capsule preparation capable of realizing high oxidation stability and high oral absorbability by filling a hard capsule such as gelatin as a slurry suspended therein.

  Usually, a hard capsule preparation containing reduced coenzyme Q10 is assumed to be a preparation obtained by filling a hard capsule such as gelatin with a powder composition containing reduced coenzyme Q10 powder. However, in this preparation, similarly to the soft capsule preparation, the invasion of oxygen from the outside is only physically shielded only by the capsule shell, and the reduced coenzyme Q10 filled even after the preparation is prepared. Can be easily oxidized.

  On the other hand, in a hard capsule preparation obtained by filling a particulate composition containing the reduced coenzyme Q10 of the present invention into a hard capsule such as gelatin, the reduced coenzyme Q10 is not only a capsule shell but also a water-soluble additive. It is possible to physically shield the entry of oxygen from the outside with a double film combined with the shape layer, and to obtain a reduced coenzyme Q10 preparation that is more stable against oxidation.

  Needless to say, other components may be optionally added so that the oral absorbability of the reduced coenzyme Q10 of the present invention is good, or a mixture with any other active ingredient may be used.

  In the present invention, the particulate composition of the present invention can be processed into a tablet or chewable agent together with any excipient, lubricant and the like.

  In general, as a tablet or chewable agent containing reduced coenzyme Q10, a preparation obtained by processing a composition obtained by directly mixing reduced coenzyme Q10 powder with an excipient or the like by tableting or the like is assumed. . However, in this preparation, naked reduced coenzyme Q10 powder is only dispersed and distributed in a composition containing an excipient such as lactose and a lubricant such as magnesium stearate and crystalline cellulose. Since the reduced coenzyme Q10 cannot be prevented from oxidation, the oxidation stability is inevitably at a low level. However, the tablet or chewable agent obtained by processing the particulate composition containing reduced coenzyme Q10 of the present invention is a water-soluble excipient matrix in which reduced coenzyme Q10 contains water-soluble ascorbic acid. Therefore, it is possible to physically block the invasion of oxygen from the outside, and to obtain a reduced coenzyme Q10 preparation that is more stable against oxidation. Needless to say, other components may be optionally added so that the oral absorbability of the reduced coenzyme Q10 of the present invention is good, or a mixture with any other active ingredient may be used. In addition, the tablet or chewable preparation of the present invention can be coated with sugar coating or the like, if necessary.

  In addition, from the viewpoint of the stability of the particulate composition containing reduced coenzyme Q10, the above preparation is also handled in an environment where the relative humidity is adjusted as described above, and / or as described above. It is a preferable aspect to handle the product by carrying out proper packaging.

  Furthermore, the particulate composition of the present invention can be used as it is or dissolved and / or dispersed in water and used in foods such as jelly and yogurt, beverages, cosmetics, etc. containing reduced coenzyme Q10. I can do it. Moreover, the particulate composition of the present invention can be directly dissolved and / or dispersed in a commercially available beverage, cosmetic or the like. In each production process of these foods, beverages or cosmetics, in some cases, the particulate composition of the present invention is disintegrated in water, and the oil component containing the reduced coenzyme Q10 in the domain portion has a volume average particle size of 0. It becomes fine particles of 01 to 50 μm and is dispersed in the product. Thus, by using the particulate composition of the present invention, reduced coenzyme Q10 can be stored in a product while it can be stored in a state of good oxidation stability until immediately before production of the product. Not only can it be in a finely dispersed state with a very small particle size, but a reduced coenzyme Q10-containing emulsion composition can be obtained under mild stirring conditions without using a large-scale emulsifying apparatus.

  The emulsified particle size of the oil component at this time can also be measured by the above-described commercially available dynamic light scattering particle size distribution measuring device or laser diffraction / scattering particle size distribution measuring device.

  The particulate composition of the present invention includes the above-mentioned forms and other forms, foods (general foods, nutritional functional foods, foods for specified health use, nutritional supplements, nutritional agents), animal drugs, beverages, feeds, It can be widely used in applications such as pet foods, cosmetics, pharmaceuticals, therapeutic drugs, preventive drugs and the like, or processing them into raw materials and compositions.

  EXAMPLES Next, although this invention is demonstrated further in detail based on an Example, this invention is not limited only to this Example.

(Purity of reduced coenzyme Q10)
The purity of reduced coenzyme Q10, the weight ratio of oxidized coenzyme Q10 and reduced coenzyme Q10, etc. were determined by the following HPLC analysis. The HPLC analysis conditions are described below.

Column: SYMMETRY C18 (manufactured by Waters) 250 mm (length) 4.6 mm (inner diameter), mobile phase; C ₂ H ₅ OH / CH ₃ OH = 4/3 (v / v), detection wavelength: 210 nm, flow rate: 1 0.0 ml / min, retention time of reduced coenzyme Q10; 9.1 min, retention time of oxidized coenzyme Q10; 13.3 min.

(Sphericity)
The sphericity of the obtained particulate composition is determined by analyzing the image obtained by electron microscope observation of the recovered particles with image analysis software (WinROOF Ver. 3.30), and the diameter and circumscribing of a circle having the same area. It was calculated from the diameter ratio of the smallest circle. In the analysis, 20 samples were analyzed and the average value was obtained.

(Crystallinity)
The crystallinity of reduced coenzyme Q10 in the obtained particulate composition was determined by analyzing the following DSC (Differential Scanning Calorimeter [EXSTAR6000 manufactured by Seiko Denshi Kogyo Co., Ltd.]) after storage at 25 ° C. in air for 30 days. Determined by doing. After storing the particulate compositions obtained in Examples and Comparative Examples under the above-mentioned predetermined conditions, 10 mg of them are taken into an aluminum pan and heated from 15 ° C. to 70 ° C. at a temperature rising rate of 5 ° C./min. The heat of crystal melting at that time was measured. The degree of crystallinity is calculated from the following formula: theoretical heat of fusion determined from the content of reduced coenzyme Q10 in the particulate composition, and data of heat of fusion measured by DSC:
Crystallinity (%) = (Measured heat of fusion / Theoretical heat of fusion) × 100
Calculated according to

(Volume average particle diameter)
The volume average particle size of the obtained particulate composition was measured using an ethanol solvent in a laser diffraction / scattering type particle size distribution measuring apparatus (Nikkiso Co., Ltd .; Microtrack MT3000II, or Horiba, Ltd .; 950). did.

(Emulsified particle size)
The emulsified particle diameter of the oil component (A) in the obtained oil-in-water emulsion composition was measured with a dynamic light scattering particle size distribution analyzer (manufactured by Horiba, Ltd .; LB-550).

(Domain average particle size)
The obtained particulate composition was added to a two-component curable adhesive (manufactured by AZONE Corporation; Araldite) and then cured. The obtained embedded sample was immersed in liquid nitrogen for 5 minutes and sufficiently cooled, and then fractured using a hammer. The fracture surface was immersed in hexane for 15 minutes, and after removing the oil component (A), the fracture surface of the particulate composition was photographed with a scanning electron microscope (manufactured by Hitachi High-Technologies Corporation; S-4800). The average particle diameter of the domain was obtained by arbitrarily selecting 50 holes from an image taken at random, measuring the particle diameter, and averaging.

(Measurement of true specific gravity)
The true specific gravity of the obtained particulate composition was measured by a liquid phase substitution method. Details are shown below. In the liquid phase substitution method, measurement was performed using AUTO TRUE DENSER MAT-7000 (manufactured by Seishin Enterprise Co., Ltd.) under the conditions of dry ethanol solvent and 25 ± 2 ° C.

Reduced coenzyme Q10 dissolved by heating at 60 ° C. was diluted in a 20 cc volumetric flask in an atmosphere at 60 ° C., and the weight of reduced coenzyme Q10 in a liquid state was measured. From the obtained weight value, the density of reduced coenzyme Q10 in a liquid state was calculated and found to be 0.925 g / cm ³ . This value was used as a representative value for the density of reduced coenzyme Q10 required for calculating the true specific gravity of the water-soluble excipient component.

The obtained particulate composition was heated at 100 ° C. for 2 hours to adjust the moisture content (volatile content) of the particulate composition to 3% by weight or less. Thereafter, the true specific gravity of the particulate composition after moisture adjustment was measured under the above conditions to obtain the true specific gravity d of the particulate composition. The true specific gravity of the water-soluble excipient component is the true specific gravity d of the particulate composition, the density of the oily component (A) (0.925 g / cm ^{3 in} the case of reduced coenzyme Q10 alone), in the particulate composition From the content c (% by weight) of the oil component (A), the following formula:
True specific gravity of water-soluble excipient component = [d − {(c / 100) × 0.925}] / [(100−c) / 100]
Calculated according to

(Production Example 1)
In 1000 g of ethanol, 100 g of oxidized coenzyme Q10 crystal (manufactured by Kaneka Corporation) and 60 g of L-ascorbic acid were added and stirred at 78 ° C. to carry out a reduction reaction. After 30 hours, the mixture was cooled to 50 ° C., and 400 g of ethanol and 100 g of water were added while maintaining the same temperature. While stirring this ethanol solution, it was cooled to 2 ° C. at a cooling rate of 10 ° C./hour to obtain a white slurry. The obtained slurry was filtered under reduced pressure, the wet crystals were washed with cold ethanol and cold water in this order, and the wet crystals were dried under reduced pressure to obtain 95 g of white dry crystals (solid yield 95 mol%). All operations except for drying under reduced pressure were performed in a nitrogen atmosphere. The purity of the obtained crystal was 99.1%, and the weight ratio of reduced coenzyme Q10 / oxidized coenzyme Q10 was 99.5 / 0.5.

Example 1
In 140 g of distilled water, 60 g of gum arabic (manufactured by Ina Food Industry Co., Ltd .; gum arabic A) and 1.9 g of L (+)-ascorbic acid (manufactured by Wako Pure Chemical Industries, Ltd.) are dissolved at 60 ° C. An aqueous excipient solution was prepared. This aqueous solution was kept at 60 ° C., and 9.2 g of reduced coenzyme Q10 powder obtained in the above Production Example 1 was added and melted, and then 10000 revolutions × 5 with a TK homomixer Mark II (manufactured by PRIMIX Corporation). The mixture was emulsified for a minute to obtain an oil-in-water emulsion composition. The emulsion particle size of reduced coenzyme Q10 in the oil-in-water emulsion composition was about 1 μm. 75 g of the oil-in-water emulsion composition obtained here was heated to 90 ° C. in advance, 100 g of MCT (manufactured by Riken Vitamin Co., Ltd .; Actor M-2) and tetraglycerin pentaoleate (manufactured by Sakamoto Yakuhin Kogyo Co., Ltd.) SY Glyster PO-3S, HLB3.0) was added to the oil component (B) consisting of 50 g, and the stirring rotation speed was adjusted so that the oil-in-water emulsion composition was suspended in the oil component (B). While the stirring is continued, the temperature of the suspension is adjusted to 105 ° C., so that the removal of water from the oil-in-water emulsion composition suspension droplets proceeds. As a result, most of the water is removed in about 30 minutes. Evaporated. Thereafter, according to a conventional method, the oily component (B) is separated by solid-liquid separation, and the oily component (B) adhering to the particles is washed with about 500 g of ethanol and then dried at 50 ° C. A particulate composition containing Q10 was obtained.

  The resulting particulate composition had a sphericity of 0.97, a volume average particle size of about 200 μm, a content of coenzyme Q in the particulate composition of 12.6% by weight, and reduced coenzyme Q10 / oxidized type. The weight ratio of coenzyme Q10 was 99.7 / 0.3. Further, the retention rate of reduced coenzyme Q10 after sealing the particulate composition in a glass bottle and storing it for 90 days under light-shielding conditions at 40 ° C. was 97.8%. In addition, the retention rate of reduced coenzyme Q10 after storage for 30 days in the environment of 40 ° C. and relative humidity of 80% in the air (open) and under light-shielding conditions was 97.7%. Furthermore, the crystallinity of reduced coenzyme Q10 in the particulate composition measured by DSC is 0%, and contains 100% by weight of reduced coenzyme Q10 in an amorphous state or a melt state. It was.

  When the appearance of the obtained particulate composition was observed with a scanning electron microscope (manufactured by Hitachi High-Technologies Corporation; S-4800), it was found that it had a very clean spherical shape as shown in FIG. Further, the fracture surface of the obtained particulate composition was immersed in hexane to dissolve and remove reduced coenzyme Q10, and then observed with a scanning electron microscope. As shown in FIG. It was found that there was evidence that the oil component (A) containing reduced coenzyme Q10 formed at least 100 domains and polydispersed in the matrix as the main component. The average particle size of the domain of the oil component (A) is about 1 μm, and the emulsion particle size of the reduced coenzyme Q10 in the oil-in-water emulsion composition in the production process is maintained even after the particle preparation. I understood that.

(Comparative Example 1)
In 140 g of distilled water, 60 g of gum arabic (manufactured by Ina Food Industry Co., Ltd .; gum arabic A) was dissolved at 30 ° C. to prepare a water-soluble excipient aqueous solution. After this aqueous solution was heated to 60 ° C., 9.2 g of reduced coenzyme Q10 powder obtained in Production Example 1 was added and melted, and then 10000 revolutions by TK homomixer Mark II (manufactured by Primics Co., Ltd.) Emulsification for 5 minutes gave an oil-in-water emulsion composition. The emulsion particle size of reduced coenzyme Q10 in the oil-in-water emulsion composition was about 1 μm. 75 g of the oil-in-water emulsion composition obtained here was heated to 90 ° C. in advance, 100 g of MCT (manufactured by Riken Vitamin Co., Ltd .; Actor M-2) and tetraglycerin pentaoleate (manufactured by Sakamoto Yakuhin Kogyo Co., Ltd.) SY glister PO-3S, HLB 3.0) was added to the oil component (B) consisting of 50 g, and the stirring rotation speed was adjusted to the same conditions as in Example 1. The water temperature was removed from the oil-in-water emulsion composition suspension droplets by adjusting the temperature of the suspension to 105 ° C. while continuing the stirring, and as a result, most of the water evaporated in about 30 minutes. . Thereafter, according to a conventional method, the oily component (B) is separated by solid-liquid separation, and the oily component (B) adhering to the particles is washed with about 500 g of ethanol and then dried at 50 ° C. A particulate composition containing Q10 was obtained.

  The obtained particulate composition has a volume average particle diameter of about 200 μm, the content of coenzyme Q in the particulate composition is 13.0% by weight, and the weight of reduced coenzyme Q10 / oxidized coenzyme Q10. The ratio was 99.2 / 0.8. Further, the retention rate of reduced coenzyme Q10 after sealing the particulate composition in a glass bottle and storing it for 90 days under light-shielding conditions at 40 ° C. was 95.8%. In addition, the retention rate of reduced coenzyme Q10 after storage for 30 days under light-shielding conditions in an environment of 40 ° C. in the air (open) and relative humidity of 80% was 77.6%.

(Example 2)
In 140 g of distilled water, 60 g of gum arabic (manufactured by Ina Food Industry Co., Ltd .; gum arabic A) and 1.9 g of L (+)-ascorbic acid (manufactured by Wako Pure Chemical Industries, Ltd.) are dissolved at 60 ° C. An aqueous excipient solution was prepared. Separately, 9.2 g of reduced coenzyme Q10 powder obtained in Production Example 1 above and 4.6 g of diglycerin monooleate (RIKEN Vitamin Co., Ltd .; Poem DO-100V) were uniformly mixed at 60 ° C. Component (a) was added to an aqueous water-soluble excipient solution at 60 ° C., and emulsified with a TK homomixer Mark II (manufactured by Primics Co., Ltd.) at 10,000 rpm for 5 minutes to obtain an oil-in-water emulsion composition. The oil-based component (a) containing reduced coenzyme Q10 in the oil-in-water emulsion composition had an emulsion particle size of about 0.5 μm. 75 g of the oil-in-water emulsion composition obtained here was heated to 90 ° C. in advance, 100 g of MCT (manufactured by Riken Vitamin Co., Ltd .; Actor M-2) and tetraglycerin pentaoleate (manufactured by Sakamoto Yakuhin Kogyo Co., Ltd.) SY glister PO-3S, HLB3.0) was added to 50 g of oil component (B) and stirred. While the stirring is continued, the temperature of the suspension is adjusted to 105 ° C., so that the removal of water from the oil-in-water emulsion composition suspension droplets proceeds. As a result, most of the water is removed in about 30 minutes. Evaporated. Thereafter, according to a conventional method, the oily component (B) is separated by solid-liquid separation, and the oily component (B) adhering to the particles is washed with about 500 g of ethanol and then dried at 50 ° C. A particulate composition containing Q10 was obtained.

  The resulting granular composition had a sphericity of 0.96, a volume average particle size of about 200 μm, a content of coenzyme Q in the particulate composition of 11.9% by weight, and reduced coenzyme Q10 / oxidized type. The weight ratio of coenzyme Q10 was 99.6 / 0.4. Moreover, the average particle diameter of the domain of the oily component (A) in the particulate composition is about 0.5 μm, and the oily component containing the reduced coenzyme Q10 in the oil-in-water emulsion composition in the production process ( It was found that the emulsified particle diameter of a) was maintained after the particle preparation. Further, the retention rate of reduced coenzyme Q10 after sealing the particulate composition in a glass bottle and storing it for 90 days under light-shielding conditions at 40 ° C. was 98.2%. The retention of reduced coenzyme Q10 after storage for 30 days under light-shielding conditions in an environment of 40 ° C., in the air (open), and relative humidity of 80% was 99.0%. Furthermore, the crystallinity of reduced coenzyme Q10 in the particulate composition measured by DSC is 0%, and contains 100% by weight of reduced coenzyme Q10 in an amorphous state or a melt state. It was.

(Comparative Example 2)
In 140 g of distilled water, 60 g of gum arabic (manufactured by Ina Food Industry Co., Ltd .; gum arabic A) was dissolved at 30 ° C. to prepare a water-soluble excipient aqueous solution. Separately, 9.2 g of reduced coenzyme Q10 powder obtained in Production Example 1 above and 4.6 g of diglycerin monooleate (RIKEN Vitamin Co., Ltd .; Poem DO-100V) were uniformly mixed at 60 ° C. Component (a) was added to an aqueous water-soluble excipient solution at 60 ° C., and emulsified with a TK homomixer Mark II (manufactured by Primics Co., Ltd.) at 10,000 rpm for 5 minutes to obtain an oil-in-water emulsion composition. The oil-based component (a) containing reduced coenzyme Q10 in the oil-in-water emulsion composition had an emulsion particle size of about 0.5 μm. 75 g of the oil-in-water emulsion composition obtained here was heated to 90 ° C. in advance, 100 g of MCT (manufactured by Riken Vitamin Co., Ltd .; Actor M-2) and tetraglycerin pentaoleate (manufactured by Sakamoto Yakuhin Kogyo Co., Ltd.) SY glister PO-3S, HLB3.0) was added to 50 g of oil component (B) and stirred. While the stirring is continued, the temperature of the suspension is adjusted to 105 ° C., so that the removal of water from the oil-in-water emulsion composition suspension droplets proceeds. As a result, most of the water is removed in about 30 minutes. Evaporated. Thereafter, according to a conventional method, the oily component (B) is separated by solid-liquid separation, and the oily component (B) adhering to the particles is washed with about 500 g of ethanol and then dried at 50 ° C. A particulate composition containing Q10 was obtained.

  The obtained particulate composition has a volume average particle diameter of about 200 μm, the content of coenzyme Q in the particulate composition is 12.2% by weight, and the weight of reduced coenzyme Q10 / oxidized coenzyme Q10. The ratio was 99.1 / 0.9. Further, the retention rate of reduced coenzyme Q10 after sealing the particulate composition in a glass bottle and storing it for 90 days under light-shielding conditions at 40 ° C. was 97.1%.

(Example 3)
In 140 g of distilled water, 60 g of gum arabic (manufactured by Ina Food Industry Co., Ltd .; gum arabic A) and 6.5 g of L (+)-ascorbic acid (manufactured by Wako Pure Chemical Industries, Ltd.) are dissolved at 60 ° C. An aqueous excipient solution was prepared. This aqueous solution was kept at 60 ° C., and 8.0 g of enzyme-decomposed lecithin (Degustex Texturant Systems Japan Co., Ltd .; Emultop HL50IP) and 31.9 g of reduced coenzyme Q10 powder obtained in Production Example 1 were added. After being dispersed, the mixture was emulsified with TK homomixer Mark II (manufactured by Primics Co., Ltd.) for 10,000 rotations × 5 minutes to obtain an oil-in-water emulsion composition. The oil-based component (a) containing reduced coenzyme Q10 in the oil-in-water emulsion composition had an emulsion particle size of about 0.5 μm. 75 g of the oil-in-water emulsion composition obtained here was previously heated to 90 ° C., 125 g of MCT (manufactured by Riken Vitamin Co., Ltd .; Actor M-2) and tetraglycerin pentaoleate (manufactured by Sakamoto Yakuhin Kogyo Co., Ltd.) SY glister PO-3S, HLB3.0) was added to 25 g of oily component (B) and stirred. While the stirring is continued, the temperature of the suspension is adjusted to 105 ° C., so that the removal of water from the oil-in-water emulsion composition suspension droplets proceeds. As a result, most of the water is removed in about 30 minutes. Evaporated. Thereafter, according to a conventional method, the oily component (B) is separated by solid-liquid separation, and the oily component (B) adhering to the particles is washed with about 500 g of ethanol and then dried at 50 ° C. A particulate composition containing Q10 was obtained.

  The resulting particulate composition had a sphericity of 0.96, a volume average particle size of about 200 μm, a content of coenzyme Q in the particulate composition of 29.6% by weight, and reduced coenzyme Q10 / oxidized type. The weight ratio of coenzyme Q10 was 99.6 / 0.4. Further, the retention rate of reduced coenzyme Q10 after the particulate composition was sealed in a glass bottle and stored for 90 days under light-shielding conditions at 40 ° C. was 99.9%. The retention of reduced coenzyme Q10 after storage for 30 days under light-shielding conditions in an environment of 40 ° C., in the air (open), and relative humidity of 80% was 99.0%. Furthermore, the crystallinity of reduced coenzyme Q10 in the particulate composition measured by DSC is 0%, and contains 100% by weight of reduced coenzyme Q10 in an amorphous state or a melt state. It was.

(Comparative Example 3)
In 140 g of distilled water, 60 g of gum arabic (manufactured by Ina Food Industry Co., Ltd .; gum arabic A) was dissolved at 30 ° C. to prepare a water-soluble excipient aqueous solution. After heating this aqueous solution to 60 ° C., 5.3 g of enzyme-decomposed lecithin (Degustex Texturant Systems Japan Co., Ltd .; Emultop HL50IP), 10.6 g of reduced coenzyme Q10 powder obtained in Production Example 1 above, After adding and dispersing, the mixture was emulsified with TK homomixer Mark II (manufactured by PRIMIX Co., Ltd.) for 10,000 rotations × 5 minutes to obtain an oil-in-water emulsion composition. The emulsified particle size of the oil component containing reduced coenzyme Q10 in the oil-in-water emulsion composition was about 0.5 μm. 75 g of the oil-in-water emulsion composition obtained here was previously heated to 90 ° C., 125 g of MCT (Actor M-2 manufactured by Riken Vitamin Co., Ltd.) and tetraglycerin pentaoleate (manufactured by Sakamoto Yakuhin Kogyo Co., Ltd.); SY Glyster PO-3S, HLB3.0) was added to 25 g of oil component (B) and stirred. While the stirring is continued, the temperature of the suspension is adjusted to 105 ° C., so that the removal of water from the oil-in-water emulsion composition suspension droplets proceeds. As a result, most of the water is removed in about 30 minutes. Evaporated. Thereafter, according to a conventional method, the oily component (B) is separated by solid-liquid separation, and the oily component (B) adhering to the particles is washed with about 500 g of ethanol and then dried at 50 ° C. A particulate composition containing Q10 was obtained.

  The obtained particulate composition has a volume average particle diameter of about 200 μm, the content of coenzyme Q in the particulate composition is 13.7% by weight, and the weight of reduced coenzyme Q10 / oxidized coenzyme Q10. The ratio was 99.0 / 1.0. Further, the retention rate of reduced coenzyme Q10 after sealing the particulate composition in a glass bottle and storing it for 90 days under light-shielding conditions at 40 ° C. was 95.2%.

Example 4
In 140 g of distilled water, 60 g of gum arabic (manufactured by Ina Food Industry Co., Ltd .; gum arabic A) and 6.5 g of L (+)-ascorbic acid (manufactured by Wako Pure Chemical Industries, Ltd.) are dissolved at 60 ° C. An aqueous excipient solution was prepared. This aqueous solution was kept at 60 ° C., and 8.0 g of lecithin (Degustex Texturants Japan Co., Ltd .; Emulper IP) and 31.9 g of reduced coenzyme Q10 powder obtained in Production Example 1 were added and dispersed. Then, the mixture was emulsified with TK homomixer Mark II (manufactured by PRIMIX Co., Ltd.) at 10,000 rotations × 5 minutes to obtain an oil-in-water emulsion composition. The oil-based component (a) containing reduced coenzyme Q10 in the oil-in-water emulsion composition had an emulsion particle size of about 0.5 μm. 75 g of the oil-in-water emulsion composition obtained here was previously heated to 90 ° C., 125 g of MCT (manufactured by Riken Vitamin Co., Ltd .; Actor M-2) and tetraglycerin pentaoleate (manufactured by Sakamoto Yakuhin Kogyo Co., Ltd.) SY glister PO-3S, HLB3.0) was added to 25 g of oily component (B) and stirred. While the stirring is continued, the temperature of the suspension is adjusted to 105 ° C., so that the removal of water from the oil-in-water emulsion composition suspension droplets proceeds. As a result, most of the water is removed in about 30 minutes. Evaporated. Thereafter, according to a conventional method, the oily component (B) is separated by solid-liquid separation, and the oily component (B) adhering to the particles is washed with about 500 g of ethanol and then dried at 50 ° C. A particulate composition containing Q10 was obtained.

  The resulting particulate composition had a sphericity of 0.96, a volume average particle size of about 200 μm, a content of coenzyme Q in the particulate composition of 29.6% by weight, and reduced coenzyme Q10 / oxidized type. The weight ratio of coenzyme Q10 was 99.5 / 0.5. Further, the retention rate of reduced coenzyme Q10 after sealing the particulate composition in a glass bottle and storing it for 90 days under light-shielding conditions at 40 ° C. was 98.3%. The retention of reduced coenzyme Q10 after storage for 30 days under light-shielding conditions in an environment of 40 ° C., in the air (open), and relative humidity of 80% was 99.6%. Furthermore, the crystallinity of reduced coenzyme Q10 in the particulate composition measured by DSC is 0%, and contains 100% by weight of reduced coenzyme Q10 in an amorphous state or a melt state. It was.

(Comparative Example 4)
In 140 g of distilled water, 60 g of gum arabic (manufactured by Ina Food Industry Co., Ltd .; gum arabic A) was dissolved at 30 ° C. to prepare a water-soluble excipient aqueous solution. After heating this aqueous solution to 60 ° C., 5.3 g of lecithin (manufactured by Degustex Texturants Japan Co., Ltd .; Emulper IP) and 10.6 g of reduced coenzyme Q10 powder obtained in Production Example 1 were added. After being dispersed, the mixture was emulsified with TK homomixer Mark II (manufactured by PRIMIX Co., Ltd.) at 10000 rpm for 5 minutes to obtain an oil-in-water emulsion composition. The oil-based component (a) containing reduced coenzyme Q10 in the oil-in-water emulsion composition had an emulsion particle size of about 0.5 μm. 75 g of the oil-in-water emulsion composition obtained here was previously heated to 90 ° C., 125 g of MCT (Actor M-2 manufactured by Riken Vitamin Co., Ltd.) and tetraglycerin pentaoleate (manufactured by Sakamoto Yakuhin Kogyo Co., Ltd.); SY Glyster PO-3S, HLB3.0) was added to 25 g of oil component (B) and stirred. While the stirring is continued, the temperature of the suspension is adjusted to 105 ° C., so that the removal of water from the oil-in-water emulsion composition suspension droplets proceeds. As a result, most of the water is removed in about 30 minutes. Evaporated. Thereafter, according to a conventional method, the oily component (B) is separated by solid-liquid separation, and the oily component (B) adhering to the particles is washed with about 500 g of ethanol and then dried at 50 ° C. A particulate composition containing Q10 was obtained.

  The obtained particulate composition has a volume average particle diameter of about 200 μm, the content of coenzyme Q in the particulate composition is 13.7% by weight, and the weight of reduced coenzyme Q10 / oxidized coenzyme Q10. The ratio was 99.1 / 0.9. Further, the retention rate of reduced coenzyme Q10 after sealing the particulate composition in a glass bottle and storing it for 90 days under light-shielding conditions at 40 ° C. was 94.6%.

(Example 5)
In 140 g of distilled water, 60 g of gum arabic (manufactured by Ina Food Industry Co., Ltd .; gum arabic A) and 6.0 g of L (+)-ascorbic acid (manufactured by Wako Pure Chemical Industries, Ltd.) are dissolved at 60 ° C. An aqueous excipient solution was prepared. This aqueous solution was kept at 60 ° C., and 4.0 g of diglycerin monooleate (manufactured by Riken Vitamin Co., Ltd .; Poem DO-100V) and 30.0 g of reduced coenzyme Q10 powder obtained in Production Example 1 were added. After being dispersed, the mixture was emulsified with TK homomixer Mark II (manufactured by Primics Co., Ltd.) for 10,000 rotations × 5 minutes to obtain an oil-in-water emulsion composition. The oil-based component (a) containing reduced coenzyme Q10 in the oil-in-water emulsion composition had an emulsion particle size of about 0.5 μm. 148 g of MCT (manufactured by Riken Vitamin Co., Ltd .; Actor M-2) and enzymatically decomposed lecithin (manufactured by Degustex Texturant Systems Japan Co., Ltd.), 75 g of the oil-in-water emulsion composition obtained here, which had been heated to 90 ° C. in advance Emultop HL50IP) was added to the oil component (B) consisting of 2 g and stirred. While the stirring is continued, the temperature of the suspension is adjusted to 105 ° C., so that the removal of water from the oil-in-water emulsion composition suspension droplets proceeds. As a result, most of the water is removed in about 30 minutes. Evaporated. Thereafter, according to a conventional method, the oily component (B) is separated by solid-liquid separation, and the oily component (B) adhering to the particles is washed with about 500 g of ethanol and then dried at 50 ° C. A particulate composition containing Q10 was obtained.

  The resulting particulate composition had a sphericity of 0.96, a volume average particle size of about 200 μm, a content of coenzyme Q in the particulate composition of 29.6% by weight, and reduced coenzyme Q10 / oxidized type. The weight ratio of coenzyme Q10 was 99.6 / 0.4. In addition, the retention rate of reduced coenzyme Q10 after storage for 30 days under light-shielding conditions in an environment of 40 ° C. in air (open) and relative humidity of 80% was 99.2%. It was. Furthermore, the crystallinity of reduced coenzyme Q10 in the particulate composition measured by DSC is 0%, and contains 100% by weight of reduced coenzyme Q10 in an amorphous state or a melt state. It was.

(Comparative Example 5)
In 140 g of distilled water, 60 g of gum arabic (manufactured by Ina Food Industry Co., Ltd .; gum arabic A) was dissolved at 60 ° C. to prepare a water-soluble excipient aqueous solution. This aqueous solution is kept at 60 ° C., and 6.0 g of L (+)-ascorbyl palmitate (manufactured by Wako Pure Chemical Industries, Ltd.), diglycerin monooleate (manufactured by Riken Vitamin Co., Ltd .; Poem DO-100V). 0 g, 30.0 g of reduced coenzyme Q10 powder obtained in Production Example 1 above was added and dispersed, and then emulsified with TK homomixer Mark II (manufactured by Primics Co., Ltd.) for 10,000 rotations × 5 minutes, and oil-in-water type An emulsified composition was obtained. The oil-based component (a) containing reduced coenzyme Q10 in the oil-in-water emulsion composition had an emulsion particle size of about 0.5 μm. 148 g of MCT (manufactured by Riken Vitamin Co., Ltd .; Actor M-2) and enzymatically decomposed lecithin (manufactured by Degustex Texturant Systems Japan Co., Ltd.), 75 g of the oil-in-water emulsion composition obtained here, which had been heated to 90 ° C. in advance Emultop HL50IP) was added to the oil component (B) consisting of 2 g and stirred. While the stirring is continued, the temperature of the suspension is adjusted to 105 ° C., so that the removal of water from the oil-in-water emulsion composition suspension droplets proceeds. As a result, most of the water is removed in about 30 minutes. Evaporated. Thereafter, according to a conventional method, the oily component (B) is separated by solid-liquid separation, and the oily component (B) adhering to the particles is washed with about 500 g of ethanol and then dried at 50 ° C. A particulate composition containing Q10 was obtained.

  The obtained particulate composition has a volume average particle diameter of about 200 μm, the content of coenzyme Q in the particulate composition is 29.6% by weight, and the weight of reduced coenzyme Q10 / oxidized coenzyme Q10. The ratio was 99.5 / 0.5. In addition, the retention rate of reduced coenzyme Q10 after storage for 30 days in an environment of 40 ° C., air (open), and relative humidity of 80% under light-shielding conditions was 95.7%. It was.

(Comparative Example 6)
In 140 g of distilled water, 60 g of gum arabic (manufactured by Ina Food Industry Co., Ltd .; gum arabic A) was dissolved at 60 ° C. to prepare a water-soluble excipient aqueous solution. This aqueous solution was kept at 60 ° C., and 4.0 g of diglycerin monooleate (manufactured by Riken Vitamin Co., Ltd .; Poem DO-100V) and 30.0 g of reduced coenzyme Q10 powder obtained in Production Example 1 were added. After being dispersed, the mixture was emulsified with TK homomixer Mark II (manufactured by Primics Co., Ltd.) for 10,000 rotations × 5 minutes to obtain an oil-in-water emulsion composition. The oil-based component (a) containing reduced coenzyme Q10 in the oil-in-water emulsion composition had an emulsion particle size of about 0.5 μm. 148 g of MCT (manufactured by Riken Vitamin Co., Ltd .; Actor M-2) and enzymatically decomposed lecithin (manufactured by Degustex Texturant Systems Japan Co., Ltd.), 75 g of the oil-in-water emulsion composition obtained here, which had been heated to 90 ° C. in advance Emultop HL50IP) was added to the oil component (B) consisting of 2 g and stirred. While the stirring is continued, the temperature of the suspension is adjusted to 105 ° C., so that the removal of water from the oil-in-water emulsion composition suspension droplets proceeds. As a result, most of the water is removed in about 30 minutes. Evaporated. Thereafter, according to a conventional method, the oily component (B) is separated by solid-liquid separation, and the oily component (B) adhering to the particles is washed with about 500 g of ethanol and then dried at 50 ° C. A particulate composition containing Q10 was obtained.

  The obtained particulate composition has a volume average particle diameter of about 200 μm, the content of coenzyme Q in the particulate composition is 31.4% by weight, and the weight of reduced coenzyme Q10 / oxidized coenzyme Q10. The ratio was 99.0 / 1.0. In addition, the retention rate of reduced coenzyme Q10 after storage for 30 days in an environment of 40 ° C., air (open), and relative humidity of 80% under light-shielding conditions was 88.4%. It was.

(Example 6)
In 140 g of distilled water, 60 g of gum arabic (manufactured by Ina Food Industry Co., Ltd .; gum arabic A) and 6.0 g of L (+)-ascorbic acid (manufactured by Wako Pure Chemical Industries, Ltd.) are dissolved at 60 ° C. An aqueous excipient solution was prepared. This aqueous solution is kept at 60 ° C., and 2.0 g of enzymatically decomposed lecithin (Degustex Texturants Japan Co., Ltd .; Emultop HL50IP) and 30.0 g of reduced coenzyme Q10 powder obtained in Production Example 1 are added. After being dispersed, the mixture was emulsified with TK homomixer Mark II (manufactured by Primics Co., Ltd.) for 10,000 rotations × 5 minutes to obtain an oil-in-water emulsion composition. The oil-based component (a) containing reduced coenzyme Q10 in the oil-in-water emulsion composition had an emulsion particle size of about 0.5 μm. 148 g of MCT (manufactured by Riken Vitamin Co., Ltd .; Actor M-2) and enzymatically decomposed lecithin (manufactured by Degustex Texturant Systems Japan Co., Ltd.), 75 g of the oil-in-water emulsion composition obtained here, which had been heated to 90 ° C. in advance Emultop HL50IP) was added to the oil component (B) consisting of 2 g and stirred. While the stirring is continued, the temperature of the suspension is adjusted to 105 ° C., so that the removal of water from the oil-in-water emulsion composition suspension droplets proceeds. As a result, most of the water is removed in about 30 minutes. Evaporated. Thereafter, according to a conventional method, the oily component (B) is separated by solid-liquid separation, and the oily component (B) adhering to the particles is washed with about 500 g of ethanol and then dried at 50 ° C. A particulate composition containing Q10 was obtained.

  The obtained granular composition had a sphericity of 0.96 and a volume average particle size of about 200 μm. Moreover, the average particle diameter of the domain of the oily component (A) in the particulate composition is about 0.5 μm, and the oily component containing the reduced coenzyme Q10 in the oil-in-water emulsion composition in the production process ( It was found that the emulsified particle diameter of a) was maintained after the particle preparation. The content of coenzyme Q in the obtained particulate composition was 29.5% by weight, and the weight ratio of reduced coenzyme Q10 / oxidized coenzyme Q10 was 99.7 / 0.3. In addition, the retention rate of reduced coenzyme Q10 after storage for 30 days under light-shielding conditions in an environment of 40 ° C. in air (open) and 80% relative humidity was 99.0%. It was. Furthermore, the crystallinity of reduced coenzyme Q10 in the particulate composition measured by DSC is 0%, and contains 100% by weight of reduced coenzyme Q10 in an amorphous state or a melt state. It was.

(Comparative Example 7)
In 140 g of distilled water, 60 g of gum arabic (manufactured by Ina Food Industry Co., Ltd .; gum arabic A) was dissolved at 60 ° C. to prepare a water-soluble excipient aqueous solution. This aqueous solution is kept at 60 ° C., 6.0 g of L (+)-ascorbyl palmitate (manufactured by Wako Pure Chemical Industries, Ltd.), enzyme-degraded lecithin (manufactured by Degustex Textile Systems Japan Co., Ltd .; Emultop HL50IP) 0 g, 30.0 g of reduced coenzyme Q10 powder obtained in Production Example 1 above was added and dispersed, and then emulsified with TK homomixer Mark II (manufactured by Primics Co., Ltd.) for 10,000 rotations × 5 minutes, and oil-in-water type An emulsified composition was obtained. The oil-based component (a) containing reduced coenzyme Q10 in the oil-in-water emulsion composition had an emulsion particle size of about 0.5 μm. 148 g of MCT (manufactured by Riken Vitamin Co., Ltd .; Actor M-2) and enzymatically decomposed lecithin (manufactured by Degustex Texturant Systems Japan Co., Ltd.), 75 g of the oil-in-water emulsion composition obtained here, which had been heated to 90 ° C. in advance Emultop HL50IP) was added to the oil component (B) consisting of 2 g and stirred. While the stirring is continued, the temperature of the suspension is adjusted to 105 ° C., so that the removal of water from the oil-in-water emulsion composition suspension droplets proceeds. As a result, most of the water is removed in about 30 minutes. Evaporated. Thereafter, according to a conventional method, the oily component (B) is separated by solid-liquid separation, and the oily component (B) adhering to the particles is washed with about 500 g of ethanol and then dried at 50 ° C. A particulate composition containing Q10 was obtained.

  The obtained particulate composition has a volume average particle diameter of about 200 μm, the content of coenzyme Q in the particulate composition is 29.5% by weight, and the weight of reduced coenzyme Q10 / oxidized coenzyme Q10. The ratio was 99.4 / 0.6. In addition, the retention rate of reduced coenzyme Q10 after storage for 30 days in an environment of 40 ° C., in the air (open), and relative humidity of 80% under light-shielding conditions was 97.5%. It was.

(Comparative Example 8)
In 140 g of distilled water, 60 g of gum arabic (manufactured by Ina Food Industry Co., Ltd .; gum arabic A) was dissolved at 60 ° C. to prepare a water-soluble excipient aqueous solution. This aqueous solution is kept at 60 ° C., and 2.0 g of enzymatically decomposed lecithin (Degustex Texturants Japan Co., Ltd .; Emultop HL50IP) and 30.0 g of reduced coenzyme Q10 powder obtained in Production Example 1 are added. After being dispersed, the mixture was emulsified with TK homomixer Mark II (manufactured by Primics Co., Ltd.) for 10,000 rotations × 5 minutes to obtain an oil-in-water emulsion composition. The oil-based component (a) containing reduced coenzyme Q10 in the oil-in-water emulsion composition had an emulsion particle size of about 0.5 μm. 148 g of MCT (manufactured by Riken Vitamin Co., Ltd .; Actor M-2) and enzymatically decomposed lecithin (manufactured by Degustex Texturant Systems Japan Co., Ltd.), 75 g of the oil-in-water emulsion composition obtained here, which had been heated to 90 ° C. in advance Emultop HL50IP) was added to the oil component (B) consisting of 2 g and stirred. While the stirring is continued, the temperature of the suspension is adjusted to 105 ° C., so that the removal of water from the oil-in-water emulsion composition suspension droplets proceeds. As a result, most of the water is removed in about 30 minutes. Evaporated. Thereafter, according to a conventional method, the oily component (B) is separated by solid-liquid separation, and the oily component (B) adhering to the particles is washed with about 500 g of ethanol and then dried at 50 ° C. A particulate composition containing Q10 was obtained.

  The obtained particulate composition has a volume average particle diameter of about 200 μm, the content of coenzyme Q in the particulate composition is 31.9% by weight, and the weight of reduced coenzyme Q10 / oxidized coenzyme Q10. The ratio was 99.1 / 0.9. In addition, the retention rate of reduced coenzyme Q10 after storage for 30 days in an environment of 40 ° C., in the air (open) and in a relative humidity of 80% under light-shielding conditions was 88.2%. It was.

(Example 7)
In 140 g of distilled water, 53 g of gum arabic (manufactured by Ina Food Industry Co., Ltd .; gum arabic A), 6.0 g of L (+)-ascorbic acid (manufactured by Wako Pure Chemical Industries, Ltd.), dextrin (manufactured by Matsutani Chemical Industry Co., Ltd.) ; Parindex # 100) 11 g was dissolved at 60 ° C. to prepare a water-soluble excipient aqueous solution. This aqueous solution was kept at 60 ° C., and 28 g of reduced coenzyme Q10 powder obtained in Production Example 1 above, 2.0 g of oxidized coenzyme Q10 (manufactured by Kaneka Corporation) (reduced coenzyme Q10 and oxidized coenzyme) The weight ratio of Q10 was 92.4 / 7.6) added and dispersed, and then emulsified with TK homomixer Mark II (manufactured by Primics Co., Ltd.) for 10,000 rotations × 5 minutes to obtain an oil-in-water emulsion composition. . The oil-based component (a) containing coenzyme Q10 in the oil-in-water emulsion composition had an emulsion particle size of about 0.5 μm. 148 g of MCT (manufactured by Riken Vitamin Co., Ltd .; Actor M-2) and enzymatically decomposed lecithin (manufactured by Degustex Texturant Systems Japan Co., Ltd.), 75 g of the oil-in-water emulsion composition obtained here, which had been heated to 90 ° C. in advance ; Emultop HL50IP) was added to the oil component (B) consisting of 2 g, and the stirring rotation speed was adjusted so that the oil-in-water emulsion composition was suspended in the oil component (B). While the stirring is continued, the temperature of the suspension is adjusted to 105 ° C., so that the removal of water from the oil-in-water emulsion composition suspension droplets proceeds. As a result, most of the water is removed in about 30 minutes. Evaporated. Thereafter, according to a conventional method, the oily component (B) is separated by solid-liquid separation, and the oily component (B) adhering to the particles is washed with about 500 g of ethanol and then dried at 50 ° C. A particulate composition containing Q10 was obtained.

  The sphericity of the obtained particulate composition was 0.96, the volume average particle diameter was about 200 μm, the true specific gravity of the whole particulate composition was 1.30, and the true specific gravity of the water-soluble excipient component obtained by calculation was The value was 1.46. Moreover, the average particle diameter of the domain of the oily component (A) in the particulate composition is about 0.5 μm, and the oily component containing the reduced coenzyme Q10 in the oil-in-water emulsion composition in the production process ( It was found that the emulsified particle diameter of a) was maintained after the particle preparation. Furthermore, the content of coenzyme Q in the particulate composition was 29.8% by weight, and the weight ratio of reduced coenzyme Q10 / oxidized coenzyme Q10 was 99.3 / 0.7. It was found that the ratio of reduced coenzyme Q10 was increased.

  The particulate composition was sealed in a glass bottle, and the retention rate of reduced coenzyme Q10 after storage for 90 days under light-shielding conditions at 40 ° C. was 98.3%. In addition, the retention rate of reduced coenzyme Q10 after storage for 30 days under light-shielding conditions in an environment of 40 ° C., in the air (open), and relative humidity of 80% was 98.5%. Furthermore, the crystallinity of reduced coenzyme Q10 in the particulate composition measured by DSC is 0%, and contains 100% by weight of reduced coenzyme Q10 in an amorphous state or a melt state. It was.

(Comparative Example 9)
In 140 g of distilled water, 53 g of gum arabic (manufactured by Ina Food Industry Co., Ltd .; gum arabic A) and 11 g of dextrin (manufactured by Matsutani Chemical Industry Co., Ltd .; Paindex # 100) are dissolved at 60 ° C. It was created. This aqueous solution was kept at 60 ° C., and 28 g of reduced coenzyme Q10 powder obtained in Production Example 1 and 2.0 g of oxidized coenzyme Q10 (manufactured by Kaneka Corporation) were added (reduced coenzyme Q10 and oxidized form). The weight ratio of coenzyme Q10 was 92.4 / 7.6) and dispersed, and then emulsified with TK homomixer Mark II (manufactured by Primics Co., Ltd.) at 10000 rpm for 5 minutes to obtain an oil-in-water emulsion composition. . The oil-based component (a) containing coenzyme Q10 in the oil-in-water emulsion composition had an emulsion particle size of about 0.5 μm. 148 g of MCT (manufactured by Riken Vitamin Co., Ltd .; Actor M-2) and enzymatically decomposed lecithin (manufactured by Degustex Texturant Systems Japan Co., Ltd.), 75 g of the oil-in-water emulsion composition obtained here, which had been heated to 90 ° C. in advance Emultop HL50IP) was added to the oily component (B) consisting of 2 g, and the stirring speed was adjusted under the same conditions as in Example 7. While the stirring is continued, the temperature of the suspension is adjusted to 105 ° C., so that the removal of water from the oil-in-water emulsion composition suspension droplets proceeds. As a result, most of the water is removed in about 30 minutes. Evaporated. Thereafter, according to a conventional method, the oily component (B) is separated by solid-liquid separation, and the oily component (B) adhering to the particles is washed with about 500 g of ethanol and then dried at 50 ° C. A particulate composition containing Q10 was obtained.

  The resulting particulate composition had a sphericity of 0.96, a volume average particle size of about 200 μm, a coenzyme Q content of 31.2 wt% in the particulate composition, and reduced coenzyme Q10 / oxidized type. The weight ratio of coenzyme Q10 was 91.7 / 8.3. Further, the retention rate of reduced coenzyme Q10 after sealing the particulate composition in a glass bottle and storing it for 90 days under light-shielding conditions at 40 ° C. was 97.9%. In addition, the retention rate of reduced coenzyme Q10 after storage for 30 days under light-shielding conditions in an environment of 40 ° C., in the air (open), and relative humidity of 80% was 71.9%.

(Example 8)
In 140 g of distilled water, 70 g of gum arabic (manufactured by Ina Food Industry Co., Ltd .; gum arabic A), 10 g of L (+)-ascorbic acid (manufactured by Wako Pure Chemical Industries, Ltd.), sucrose (manufactured by Wako Pure Chemical Industries, Ltd.) 10 g) was dissolved at 60 ° C. to prepare a water-soluble excipient aqueous solution. This aqueous solution was kept at 60 ° C., and 8.0 g of reduced coenzyme Q10 powder obtained in Production Example 1 above, 2.0 g of oxidized coenzyme Q10 (manufactured by Kaneka Corporation) (reduced coenzyme Q10 and oxidized form) The weight ratio of coenzyme Q10 was 92.7 / 7.3) and dispersed, and then emulsified with TK homomixer Mark II (manufactured by PRIMIX Co., Ltd.) at 10000 rpm for 5 minutes to give an oil-in-water emulsion composition. Obtained. The oil-based component (a) containing coenzyme Q10 in the oil-in-water emulsion composition had an emulsion particle size of about 0.5 μm. 148 g of MCT (manufactured by Riken Vitamin Co., Ltd .; Actor M-2) and enzymatically decomposed lecithin (manufactured by Degustex Texturant Systems Japan Co., Ltd.), 75 g of the oil-in-water emulsion composition obtained here, which had been heated to 90 ° C. in advance Emultop HL50IP) was added to the oil component (B) consisting of 2 g and stirred. While the stirring is continued, the temperature of the suspension is adjusted to 105 ° C., so that the removal of water from the oil-in-water emulsion composition suspension droplets proceeds. As a result, most of the water is removed in about 30 minutes. Evaporated. Thereafter, according to a conventional method, the oily component (B) is separated by solid-liquid separation, and the oily component (B) adhering to the particles is washed with about 500 g of ethanol and then dried at 50 ° C. A particulate composition containing Q10 was obtained.

  The resulting particulate composition had a sphericity of 0.96, a volume average particle size of about 200 μm, a content of coenzyme Q in the particulate composition of 9.9% by weight, and reduced coenzyme Q10 / oxidized type. The weight ratio of coenzyme Q10 was 99.3 / 0.7, indicating that the ratio of reduced coenzyme Q10 was higher than the weight ratio used during production.

(Comparative Example 9)
The white dried crystals of reduced coenzyme Q10 obtained in Production Example 1 were pulverized in a mortar to obtain reduced coenzyme Q10 powder. The retention of reduced coenzyme Q10 in the obtained reduced coenzyme Q10 powder after storage for 30 days under light-shielding conditions at 40 ° C. was 28%.

Example 9
In 300 g of distilled water, 80 g of gum arabic (Gala gum A from Ina Food Industry Co., Ltd.) and 10 g of L-ascorbic acid were dissolved at 30 ° C. to prepare a water-soluble aqueous excipient solution. After heating this aqueous solution to 60 ° C., 10 g of reduced coenzyme Q10 powder obtained in Preparation Example 1 above was added and melted, and then 10000 rotation × 5 minutes with TK Homomixer Mark II (manufactured by Primics Co., Ltd.). Emulsification was performed to obtain an oil-in-water emulsion composition. The emulsion particle diameter (average particle diameter of the domain) of reduced coenzyme Q10 in the oil-in-water emulsion composition was about 1 μm. The oil-in-water emulsified composition is spray dried using a spray dryer (B-290 manufactured by Nihon Büch Co., Ltd.) at a temperature of hot air of 200 ° C. to obtain a particulate composition containing reduced coenzyme Q10. Obtained.

  The obtained particulate composition had a sphericity of 0.85, a volume average particle diameter of 7.1 μm, a content of coenzyme Q in the particulate composition was 10.0% by weight, and a reduced coenzyme. The weight ratio of Q10 / oxidized coenzyme Q10 was 99.6 / 0.4.

(Example 10: Oral absorbability test)
The particulate composition containing reduced coenzyme Q10 obtained in Example 7 and the reduced coenzyme Q10 powder obtained in Production Example 1 were each encapsulated in a hard capsule of gelatin, and 14 weeks old male Sprague-Dawley rats: was orally administered at a dose of 10 mg / kg as reduced coenzyme _{Q 10,} respectively (available source Nippon SLC, Inc.). Blood was collected from each rat 1, 2, 3, 4, 6 and 10 hours after administration of the test substance. The collected blood was centrifuged to obtain plasma. Thereafter, oxidation of reduced coenzyme Q ₁₀ in plasma, and performs a process of extracting oxidized coenzyme Q _10, was measured coenzyme Q ₁₀ concentration in plasma using HPLC as oxidized coenzyme Q ₁₀ . The results are shown in FIG.

  From the above results, it was found that the particulate composition containing the reduced coenzyme Q10 of the present invention was a particulate composition having both high stability and high oral absorbability.

(Example 11: Soft capsule)
The particulate composition containing reduced coenzyme Q10 obtained in Example 3 above is added to a mixture consisting of safflower oil and beeswax to form a slurry, and encapsulated in a conventional manner. A gelatin soft capsule preparation was obtained.

Particulate composition containing reduced coenzyme Q10 30 parts by weight Safflower oil 65 parts by weight Beeswax 5 parts by weight.

(Example 12: Hard capsule)
The particulate composition containing reduced coenzyme Q10 obtained in Example 3 above was singly encapsulated in a hard capsule by a conventional method to obtain a hard capsule preparation. The hard capsule was stored for 90 days under light-shielding conditions at 40 ° C. in the air (open). The retention rate of reduced coenzyme Q10 in the preparation in the capsule after storage was 99.9%.

(Comparative Example 10)
30 parts by weight of reduced coenzyme Q10 obtained in Production Example 1 and 60 parts by weight of gum arabic (manufactured by Ina Food Industry Co., Ltd .; gum arabic A) are mixed and sealed in a hard capsule by a conventional method. A formulation was obtained. The hard capsule was stored at 40 ° C. in the air for 90 days under light shielding conditions. The retention rate of reduced coenzyme Q10 in the preparation in the capsule after storage was 31.3%.

(Example 13: Tablet)
After mixing the particulate composition containing reduced coenzyme Q10 obtained in Example 3 above with crystalline cellulose (Avicel), magnesium stearate is further mixed, and tablets comprising the following components are prepared in a conventional manner. Obtained. The appearance of the obtained tablets was beautiful and no tableting problems were observed, and there were no troubles such as sticking (drug adhesion to the mortar surface) during production.

Particulate composition containing reduced coenzyme Q10 50 parts by weight Crystalline cellulose 50 parts by weight Magnesium stearate 1 part by weight

(Example 14: Chewable tablet)
The particulate composition containing reduced coenzyme Q10 obtained in Example 7 above is mixed with reduced maltose, crystalline cellulose (Avicel), glucose, lactose, magnesium stearate, and comprises the following components in a conventional manner. Tablets (chewable tablets) were obtained. The appearance of the obtained tablets was beautiful and no tableting problems were observed, and there were no troubles such as sticking (drug adhesion to the mortar surface) during production.

Particulate composition containing reduced coenzyme Q10 10 parts by weight Reduced maltose 40 parts by weight Crystalline cellulose 4 parts by weight Glucose 40 parts by weight Lactose 4 parts by weight Magnesium stearate 1 part by weight

  The chewable tablets were stored in air at 25 ° C. and a relative humidity of 60% for 30 days under open / light-shielded conditions. The retention rate of reduced coenzyme Q10 in the preparation after storage was 99.0%.

(Comparative Example 11)
The reduced coenzyme Q10 obtained in Production Example 1 above is mixed with reduced maltose, crystalline cellulose (Avicel), glucose, lactose, magnesium stearate, and a tablet (chewable tablet) comprising the following components is obtained by a conventional method. It was.

Reduced coenzyme Q10 10 parts by weight Reduced maltose 40 parts by weight Crystalline cellulose 4 parts by weight Glucose 40 parts by weight Lactose 4 parts by weight Magnesium stearate 1 part by weight

  This chewable tablet was stored in air at 25 ° C. and a relative humidity of 60% for 30 days under open / shielded conditions. The retention rate of reduced coenzyme Q10 in the preparation after storage was 70.3%.

(Example 15: Beverage)
To 500 mL of commercially available oolong tea, 100 mg of a particulate composition containing reduced coenzyme Q10 obtained in Example 7 was added and mixed to disperse the particulate composition. As a result, the matrix component in the particulate composition was dissolved, and the reduced coenzyme Q10-containing oolong tea in which the oil component containing the reduced coenzyme Q10 was emulsified was obtained. The emulsified particle size of the oil component containing reduced coenzyme Q10 at this time was about 0.5 μm.

  From the above Examples and Comparative Examples, the particulate composition of the present invention becomes a solvent such as fats and oils, emulsifiers or ethanol by containing water-soluble ascorbic acid in a matrix mainly composed of water-soluble excipients. It is contained in the particulate composition even though the components are not present at all or are completely insufficient to make the reduced coenzyme Q10 and ascorbic acid compatible at the molecular level. It can be seen that the oxygen stability of the reduced coenzyme Q10 is improved. Furthermore, it can be seen that very high oxidation stability is maintained even under high humidity conditions of 80% relative humidity.

Claims (36)

  A particulate composition in which an oily component (A) containing reduced coenzyme Q10 forms a domain and is polydispersed in a matrix containing a water-soluble excipient and water-soluble ascorbic acids.   Water-soluble ascorbic acid is ascorbic acid, rhamno-ascorbic acid, arabo-ascorbic acid, gluco-ascorbic acid, fuco-ascorbic acid, glucohepto-ascorbic acid, xylo-ascorbic acid, galacto-ascorbic acid, gulo-ascorbic acid, allo The particulate composition according to claim 1, which is at least one selected from the group consisting of ascorbic acid, erythro-ascorbic acid, 6-desoxyascorbic acid and salts thereof.   The particulate composition according to claim 1 or 2, wherein the sphericity is 0.8 or more.   The particulate composition according to any one of claims 1 to 3, wherein 10% by weight or more of the reduced coenzyme Q10 in the particulate composition is not in a crystalline state.   The particulate composition according to any one of claims 1 to 4, wherein the oily component (A) forms 5 or more domains and is polydispersed.   The ratio of the reduced coenzyme Q10 and the water-soluble ascorbic acids in the particulate composition is in the range of 100: 1 to 1: 5 by weight ratio, 6. 2. The particulate composition according to item 1.   The water-soluble excipient is one or more selected from the group consisting of a water-soluble polymer, a surfactant (C), a sugar, and a yeast cell wall, according to any one of claims 1 to 6. Particulate composition.   The group in which the water-soluble polymer is gum arabic, gelatin, agar, starch, pectin, carrageenan, casein, dried egg white, curdlan, alginic acids, soybean polysaccharide, pullulan, celluloses, xanthan gum, carmellose salt, and polyvinylpyrrolidone The particulate composition according to claim 7, wherein the particulate composition is one or more selected from the above.   The surfactant (C) is at least one selected from the group consisting of glycerin fatty acid esters, sucrose fatty acid esters, sorbitan fatty acid esters, polyoxyethylene sorbitan fatty acid esters, lecithins and saponins. The particulate composition according to claim 7.   The particulate composition according to claim 7, wherein the sugar is at least one selected from the group consisting of monosaccharides, disaccharides, oligosaccharides, sugar alcohols, and polysaccharides.   The oily component (A) containing reduced coenzyme Q10 contains 5 to 100% by weight of coenzyme Q10, 0 to 95% by weight of fat and oil, and 0 to 95% by weight of surfactant (D). The particulate composition according to any one of claims 1 to 10.   Surfactant (D) is glycerin fatty acid ester, polyglycerin ester, sucrose fatty acid ester, sorbitan fatty acid ester, polyoxyethylene sorbitan fatty acid ester and propylene glycol fatty acid ester having HLB of 10 or less, and lecithin The particulate composition according to claim 11, wherein the particulate composition is at least one selected from the group consisting of a group.   The particulate composition according to any one of claims 1 to 12, wherein the content of reduced coenzyme Q10 in the particulate composition is 1 to 70% by weight.   The particulate composition according to any one of claims 1 to 13, wherein the volume average particle diameter is 1 to 1000 µm.   The particulate composition according to any one of claims 1 to 14, wherein the average particle size of the domain formed by the oily component (A) containing reduced coenzyme Q10 is 0.01 to 50 µm.   The retention rate of reduced coenzyme Q10 in the particulate composition after storage for 30 days under light-shielding conditions at 40 ° C in the air is 80% by weight or more. Particulate composition.   The formulation obtained by processing the particulate composition of any one of Claims 1-16.   A reduced coenzyme Q10, wherein the particulate composition according to any one of claims 1 to 16 or the preparation according to claim 17 is placed in an environment having a relative humidity of 90% or less. A method for stabilizing a contained particulate composition or preparation.   The particulate composition according to any one of claims 1 to 16 or the preparation according to claim 17 is packaged and packed with a material made of glass, plastic and / or metal, A method for stabilizing a particulate composition or preparation containing reduced coenzyme Q10.   The stabilization method according to claim 18 or 19, wherein a moisture-proofing agent is used in combination.   An oil-in-water emulsion composition is prepared from an aqueous solution containing a water-soluble ascorbic acid and a water-soluble excipient and an oil component (a) containing coenzyme Q10, and then the water in the oil-in-water emulsion composition is reduced. A method for producing a particulate composition containing reduced coenzyme Q10, which comprises removing the coenzyme Q10.   The production method according to claim 21, wherein reduced coenzyme Q10 is used as coenzyme Q10 contained in oil component (a).   In the process of producing a particulate composition using oxidized coenzyme Q10 or a mixture of oxidized coenzyme Q10 and reduced coenzyme Q10 as coenzyme Q10 contained in oil component (a), coenzyme Q10 The production method according to claim 21, wherein at least a part of the oxidized coenzyme Q10 is reduced to reduced coenzyme Q10.   Water-soluble ascorbic acid is ascorbic acid, rhamno-ascorbic acid, arabo-ascorbic acid, gluco-ascorbic acid, fuco-ascorbic acid, glucohepto-ascorbic acid, xylo-ascorbic acid, galacto-ascorbic acid, gulo-ascorbic acid, allo The production method according to any one of claims 21 to 23, which is at least one selected from the group consisting of ascorbic acid, erythro-ascorbic acid, 6-desoxyascorbic acid and salts thereof.   The oil-in-water emulsion composition is suspended in the oil-based component (B), and then water in the oil-in-water emulsion composition is removed in the oil-based component (B). 24. The production method according to any one of 24.   The production method according to claim 25, wherein the oil component (B) contains 5 to 99.99% by weight of fat and oil and 0.01 to 95% by weight of the surfactant (E).   Surfactant (E) is selected from the group consisting of glycerin fatty acid esters, polyglycerin esters, sucrose fatty acid esters, sorbitan fatty acid esters and polyoxyethylene sorbitan fatty acid esters having an HLB of 10 or less, and lecithins The manufacturing method of Claim 26 which is 1 or more types.   25. The production method according to claim 21, wherein water in the oil-in-water emulsion composition is removed by spray drying the oil-in-water emulsion composition in a gas phase. .   The manufacturing method of any one of Claims 21-28 whose sphericity of the obtained particulate composition is 0.8 or more.   30. The production method according to any one of claims 21 to 29, wherein 1 to 500 parts by weight of water-soluble ascorbic acid is used with respect to 100 parts by weight of coenzyme Q10.   The production according to any one of claims 21 to 30, wherein the water-soluble excipient is at least one selected from the group consisting of a water-soluble polymer, a surfactant (C), a sugar, and a yeast cell wall. Method.   The group in which the water-soluble polymer is gum arabic, gelatin, agar, starch, pectin, carrageenan, casein, dried egg white, curdlan, alginic acids, soybean polysaccharide, pullulan, celluloses, xanthan gum, carmellose salt, and polyvinylpyrrolidone The production method according to claim 31, wherein the production method is at least one selected from the group consisting of more than one kind.   The surfactant (C) is at least one selected from the group consisting of glycerin fatty acid esters, sucrose fatty acid esters, sorbitan fatty acid esters, polyoxyethylene sorbitan fatty acid esters, lecithins and saponins. The manufacturing method according to claim 31.   32. The production method according to claim 31, wherein the sugar is at least one selected from the group consisting of monosaccharides, disaccharides, oligosaccharides, sugar alcohols, and polysaccharides.   The oil component (a) containing coenzyme Q10 contains 5 to 100% by weight coenzyme Q10, 0 to 95% by weight fat and oil, and 0 to 95% by weight surfactant (D). 21. The manufacturing method according to any one of 21 to 34.   Surfactant (D) is glycerin fatty acid ester, polyglycerin ester, sucrose fatty acid ester, sorbitan fatty acid ester, polyoxyethylene sorbitan fatty acid ester and propylene glycol fatty acid ester having HLB of 10 or less, and lecithin 36. The production method according to claim 35, wherein the production method is one or more selected from the group consisting of a group.