JP5546935B2 - Reduced coenzyme Q10-containing composition and method for producing the same - Google Patents

Description

  The present invention relates to a composition containing reduced coenzyme Q10 and a method for producing the same. Reduced coenzyme Q10 exhibits higher oral absorbability than oxidized coenzyme Q10, and is excellent food, health food, functional nutrition food, food for specified health use, supplement, nutritional supplement, nutritional supplement, beverage, feed It is a compound useful as an animal drug, cosmetics, pharmaceutical, therapeutic drug, prophylactic drug, and the like.

  Reduced coenzyme Q10 exhibits a higher oral absorbability than oxidized coenzyme Q10 and is a very useful compound as an antioxidant. For example, synthesis, fermentation, extraction from natural products and the like are conventionally known. It is a compound obtained by reducing oxidized coenzyme Q10 obtained by the method. So far, a method for producing reduced coenzyme Q10 and a composition containing reduced coenzyme Q10 using or coexisting with a reducing agent have been reported (Patent Document 1).

In this patent document 1,
1) reduced coenzyme Q10, an amount of reducing agent effective to inhibit oxidation of reduced coenzyme Q10 to oxidized coenzyme Q10, and a surfactant or vegetable oil or a mixture thereof; and A composition comprising a solvent, if necessary,
2) A composition for oral administration in which the above composition is formulated into a gelatin capsule or tablet;
3) A method for preparing the above-described composition containing reduced coenzyme Q10 in situ using oxidized coenzyme Q10 and a reducing agent is disclosed.
A composition using limonene has been reported as a high-concentration solution composition of reduced coenzyme Q10 (Patent Document 2).

  In Patent Document 2, α-lipoic acid is used as a stabilizer for stably maintaining reduced coenzyme Q10, a reducing agent for reducing oxidized coenzyme Q10, and the reduced coenzyme Q10. Limonene and fatty acids are disclosed as monoterpenes to be added in order to dissolve water, and compositions containing them and methods for preparing the same are also disclosed.

WO2001 / 52822 WO2008 / 113066

  The content of reduced coenzyme Q10 in the composition obtained by the production method of Patent Document 1 is actually in the range of 1.5% to 4% by weight. From the viewpoint of ease of design or cost reduction, there is a demand for a composition containing an even higher concentration of reduced coenzyme Q10. On the other hand, in the case of limonene described in Patent Document 2, the maximum concentration of reduced coenzyme Q10 in the composition is 23.5% by weight, and limonene relatively dissolves reduced coenzyme Q10 well. However, as a result of various studies we have conducted, the reduction reaction of oxidized coenzyme Q10 does not proceed easily in limonene, so oxidized coenzyme Q10 is reduced to obtain a high-quality reduced coenzyme Q10 composition. As a result, it has been found that the solvent is not necessarily suitable.

  Therefore, the present invention has a high solubility in oxidized coenzyme Q10 and reduced coenzyme Q10 in order to easily produce a high concentration composition of reduced coenzyme Q10 that can meet market demands, and It is an object of the present invention to provide a method for producing a reduced coenzyme Q10-containing composition using a solvent in which the reduction reaction of oxidized coenzyme Q10 proceeds well, a composition thereof, and a method for stabilizing the same.

  As a result of intensive studies, the present inventors have been able to dissolve reduced coenzyme Q10 at a high concentration by specific terpenes, and the reduction reaction of oxidized coenzyme Q10 proceeds well in the specific terpenes. In addition, the inventors have found that reduced coenzyme Q10 can be stably retained in the obtained composition, and have completed the present invention.

That is, the present invention provides an oxidized type complement using a reducing agent in the presence of at least one terpene selected from the group consisting of p-cymene, α-pinene, valencene, myrcene, bisabolene, carene, caryophyllene, terpinene and phytol. The present invention relates to a method for producing reduced coenzyme Q10, wherein enzyme Q10 is reduced.
The present invention also contains at least one terpene selected from the group consisting of p-cymene, α-pinene, valencene, myrcene, bisabolene, carene, caryophyllene, terpinene and phytol, reduced coenzyme Q10 and a reducing agent. And reduced coenzyme Q10 and reduction in the presence of at least one terpene selected from the group consisting of p-cymene, α-pinene, valencene, myrcene, bisabolen, carene, caryophyllene, terpinene and phytol The present invention relates to a method for stabilizing reduced coenzyme Q10 in the presence of an agent.

  According to the present invention, by using a specific terpene as a solvent, oxidized coenzyme Q10 can be reduced to reduced coenzyme Q10 even in a preparation, and a composition containing reduced coenzyme Q10 at a high concentration And a simple manufacturing method thereof. In addition, a method for stabilizing reduced coenzyme Q10 that is easily oxidized can be provided.

Hereinafter, the present invention will be described in detail.
First, a method for producing the reduced coenzyme Q10 of the present invention will be described. The production method of the present invention comprises oxidation using a reducing agent in the presence of at least one terpene selected from the group consisting of p-cymene, α-pinene, valencene, myrcene, bisabolen, carene, caryophyllene, terpinene and phytol. A method for producing reduced coenzyme Q10, characterized in that reduced coenzyme Q10 is reduced.

  In the production method of the present invention, the oxidized coenzyme Q10 used as a raw material may be oxidized coenzyme Q10 alone or a mixture with reduced coenzyme Q10. When the oxidized coenzyme Q10 is a mixture with the reduced coenzyme Q10, the oxidized coenzyme Q10 occupies the total amount of coenzyme Q10 (that is, the total amount of reduced coenzyme Q10 and oxidized coenzyme Q10). The ratio is not particularly limited but is, for example, 1% by weight or more, usually 5% by weight or more, preferably 10% by weight or more, more preferably 20% by weight or more, and particularly preferably 50% by weight or more. The upper limit is not particularly limited, but when a mixture of oxidized coenzyme Q10 and reduced coenzyme Q10 is used as a raw material, it is usually 99.9% by weight or less. Of course, oxidized coenzyme Q10 may be used alone. The oxidized coenzyme Q10 used here can be obtained by a conventionally known method such as synthesis, fermentation, extraction from a natural product, or the like. Preferably, it is obtained by fermentation or extraction from a natural product.

  In the production method of the present invention, when the reduction reaction is performed, a specific terpene is used as a reaction solvent in order to cause oxidized coenzyme Q10 and / or reduced coenzyme Q10 to exist in a liquid phase at a high concentration. In the production method of the present invention, the terpenes used as the reaction solvent for the reduction reaction are p-cymene, α-pinene, valencene, myrcene, bisabolen, karen, caryophyllene, terpinene, phytol, and a mixture thereof. You can also From the viewpoint of the solubility of oxidized coenzyme Q10 and reduced coenzyme Q10 and the progress of the reduction reaction, p-cymene, α-pinene, valencene, myrcene, karen, caryophyllene, and tarpinene are more preferable, and p-cymene, Valensen, myrcene, karen and caryophyllene are preferred, and p-cymene and karen are most preferred.

  In addition, other solvents can be added to the above-mentioned solvent as long as the solubility of oxidized coenzyme Q10 and reduced coenzyme Q10 and the progress of the reduction reaction are not significantly adversely affected. Other solvents used in the production method of the present invention are not particularly limited, but hydrocarbons, fatty acid esters, ethers, alcohols, ketones, fatty acids, ketones, nitrogen compounds (nitriles, amides) Organic solvents such as sulfur compounds, oils and fats, water, and the like.

  Although it does not restrict | limit especially as said hydrocarbon, For example, an aliphatic hydrocarbon, an aromatic hydrocarbon, a halogenated hydrocarbon etc. can be mentioned. In particular, an aliphatic hydrocarbon and an aromatic hydrocarbon are preferable, and an aliphatic hydrocarbon is particularly preferable.

  The aliphatic hydrocarbon is not particularly limited regardless of whether it is cyclic or non-cyclic, or saturated or unsaturated, but an acyclic aliphatic hydrocarbon is particularly preferably used. Further, those having 3 to 20 carbon atoms, preferably 5 to 12 carbon atoms are used.

  Specific examples include, for example, propane, butane, isobutane, pentane, 2-methylbutane, cyclopentane, 2-pentene, hexane, 2-methylpentane, 2,2-dimethylbutane, 2,3-dimethylbutane, and methylcyclopentane. , Cyclohexane, 1-hexene, cyclohexene, heptane, 2-methylhexane, 3-methylhexane, 2,3-dimethylpentane, 2,4-dimethylpentane, methylcyclohexane, 1-heptene, octane, 2,2,3- Examples thereof include trimethylpentane, isooctane, ethylcyclohexane, 1-octene, nonane, 2,2,5-trimethylhexane, 1-nonene, decane, 1-decene, p-menthane, undecane, dodecane and the like.

  Among these, saturated aliphatic hydrocarbons having 5 to 8 carbon atoms are preferable, pentane, 2-methylbutane, cyclopentane, hexane, 2-methylpentane, 2,2-dimethylbutane, 2,3-dimethylbutane, methylcyclopentane, Especially cyclohexane, heptane, 2-methylhexane, 3-methylhexane, 2,3-dimethylpentane, 2,4-dimethylpentane, methylcyclohexane, octane, 2,2,3-trimethylpentane, isooctane, ethylcyclohexane, etc. preferable.

  Although it does not restrict | limit especially as an aromatic hydrocarbon, Usually, a C6-C20, especially C6-C12, especially C7-C10 thing is used suitably. Specific examples include, for example, benzene, toluene, xylene, o-xylene, m-xylene, p-xylene, ethylbenzene, cumene, mesitylene, tetralin, butylbenzene, p-cymene, cyclohexylbenzene, diethylbenzene, pentylbenzene, dipentylbenzene. , Dodecylbenzene, styrene and the like. Preferably, toluene, xylene, o-xylene, m-xylene, p-xylene, ethylbenzene, cumene, mesitylene, tetralin, butylbenzene, p-cymene, cyclohexylbenzene, diethylbenzene, pentylbenzene, more preferably toluene, Xylene, o-xylene, m-xylene, p-xylene, cumene and tetralin are preferred, and cumene is most preferred.

  The halogenated hydrocarbon is not particularly limited regardless of whether it is cyclic or non-cyclic, or saturated or unsaturated. In general, a non-cyclic hydrocarbon is preferably used. Usually, chlorinated hydrocarbons and fluorinated hydrocarbons are preferable, and chlorinated hydrocarbons are particularly preferable. Those having 1 to 6 carbon atoms, particularly 1 to 4 carbon atoms, especially 1 to 2 carbon atoms are preferably used.

  Specific examples include, for example, dichloromethane, chloroform, carbon tetrachloride, 1,1-dichloroethane, 1,2-dichloroethane, 1,1,1-trichloroethane, 1,1,2-trichloroethane, 1,1,1,2 -Tetrachloroethane, 1,1,2,2-tetrachloroethane, pentachloroethane, hexachloroethane, 1,1-dichloroethylene, 1,2-dichloroethylene, trichloroethylene, tetrachloroethylene, 1,2-dichloropropane, 1,2,3- Examples thereof include trichloropropane, chlorobenzene, 1,1,1,2-tetrafluoroethane and the like.

  Preferably, dichloromethane, chloroform, carbon tetrachloride, 1,1-dichloroethane, 1,2-dichloroethane, 1,1,1-trichloroethane, 1,1,2-trichloroethane, 1,1-dichloroethylene, 1,2-dichloroethylene , Trichloroethylene, chlorobenzene, 1,1,1,2-tetrafluoroethane, more preferably dichloromethane, chloroform, 1,2-dichloroethylene, trichloroethylene, chlorobenzene, 1,1,1,2-tetrafluoroethane. .

  Although it does not restrict | limit especially as said fatty acid esters, For example, formic acid ester, acetic acid ester, propionic acid ester, butyric acid ester, isovaleric acid ester, heptanoic acid ester, hexanoic acid ester etc. can be mentioned. In particular, acetate ester and formate ester are preferable, and acetate ester is particularly preferable.

  Examples of the formate include methyl formate, ethyl formate, propyl formate, isopropyl formate, butyl formate, isobutyl formate, sec-butyl formate, pentyl formate, isoamyl formate, geranyl formate, and citronellyl formate. Preferred are ethyl formate, ethyl formate, propyl formate, isoamyl formate, geranyl formate, citronellyl formate, and most preferred is ethyl formate.

Examples of the acetate ester include methyl acetate, ethyl acetate, propyl acetate, isopropyl acetate, butyl acetate, isobutyl acetate, sec-butyl acetate, pentyl acetate, isopentyl acetate, isoamyl acetate, sec-hexyl acetate, cyclohexyl acetate, benzyl acetate, Examples thereof include amyl acetate, geranyl acetate, citronellyl acetate, cinnamyl acetate, terpinyl acetate, l-menthyl acetate, and linalyl acetate. Preferably, methyl acetate, ethyl acetate, isopropyl acetate, isoamyl acetate, cyclohexyl acetate, benzyl acetate, amyl acetate, geranyl acetate, citronellyl acetate, cinnamyl acetate, terpinyl acetate, 1-menthyl acetate, linalyl acetate, more preferably Ethyl acetate, isopropyl acetate, and butyl acetate are preferable, and ethyl acetate is most preferable.
Examples of the propionate ester include methyl propionate, ethyl propionate, butyl propionate, isopentyl propionate, isoamyl propionate, and the like.

Examples of the butyric acid ester include methyl butyrate, ethyl butyrate, butyl butyrate, isopentyl butyrate, isoamyl propionate, and cyclohexyl butyrate.
Examples of the isovaleric acid ester include methyl isovalerate, ethyl isovalerate, butyl isovalerate, isopentyl isovalerate, isoamyl isovalerate, and allyl isovalerate.

Examples of heptanoic acid esters include methyl heptanoate, ethyl heptanoate, butyl heptanoate, isopentyl heptanoate, allyl heptanoate and the like.
Examples of hexanoic acid esters include methyl hexanoate, ethyl hexanoate, butyl hexanoate, isopentyl hexanoate, and allyl hexanoate.

  The ethers are not particularly limited regardless of whether they are cyclic or non-cyclic, and whether saturated or unsaturated. In general, saturated ones are preferably used.

  Specific examples include, for example, diethyl ether, methyl tert-butyl ether, dipropyl ether, diisopropyl ether, dibutyl ether, dihexyl ether, ethyl vinyl ether, butyl vinyl ether, anisole, phenetole, butyl phenyl ether, methoxy toluene, dioxane, furan, 2 -Methyl furan, tetrahydrofuran, tetrahydropyran, ethylene glycol dimethyl ether, ethylene glycol diethyl ether, ethylene glycol dibutyl ether, ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, ethylene glycol dibutyl ether, dibenzyl ether, benzyl butyl ether, etc. it can.

  Preferably, diethyl ether, methyl tert-butyl ether, dipropyl ether, diisopropyl ether, dibutyl ether, dihexyl ether, anisole, phenetol, butyl phenyl ether, methoxytoluene, dioxane, 2-methylfuran, tetrahydrofuran, tetrahydropyran, ethylene glycol dimethyl ether , Ethylene glycol diethyl ether, ethylene glycol dibutyl ether, ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, dibenzyl ether, benzyl butyl ether, more preferably diethyl ether, methyl tert-butyl ether, diisopropyl ether, anisole, dioxane, Tetrahydrofuran, ethylene glycol Monomethyl ether, ethylene glycol monoethyl ether, dibenzyl ether, benzyl ether, more preferably diethyl ether, diisopropyl ether, dibenzyl ether, benzyl butyl ether, most preferably diisopropyl ether.

  The alcohols are not particularly limited regardless of whether they are cyclic or non-cyclic, and saturated or unsaturated. Usually, monohydric alcohols having 1 to 20 carbon atoms, dihydric alcohols, and trihydric alcohols are preferable, and monohydric alcohols having 1 to 20 carbon atoms are particularly preferable.

  Examples of the monovalent alcohol include methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, 2-butanol, isobutyl alcohol, tert-butyl alcohol, 1-pentanol, 2-pentanol, and 3-pen. Tanol, 2-methyl-1-butanol, isopentyl alcohol, tert-pentyl alcohol, 3-methyl-2-butanol, neopentyl alcohol, 1-hexanol, 2-methyl-1-pentanol, 4-methyl-2- Pentanol, 2-ethyl-1-butanol, 1-heptanol, 2-heptanol, 3-heptanol, 1-octanol, 2-octanol, 2-ethyl-1-hexanol, 1-nonanol, 1-decanol, 1-undecanol , 1-dodecanol, allyl List alcohol, propargyl alcohol, benzyl alcohol, cyclohexanol, 1-methylcyclohexanol, 2-methylcyclohexanol, 3-methylcyclohexanol, 4-methylcyclohexanol, cinnamyl alcohol, phenol, α-methylbenzyl alcohol, etc. Can do.

  Preferably, methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, 2-butanol, isobutyl alcohol, tert-butyl alcohol, 1-pentanol, 2-pentanol, 3-pentanol, 2-methyl- 1-butanol, isopentyl alcohol, tert-pentyl alcohol, 3-methyl-2-butanol, neopentyl alcohol, 1-hexanol, 2-methyl-1-pentanol, 4-methyl-2-pentanol, 2-ethyl -1-butanol, 1-heptanol, 2-heptanol, 3-heptanol, 1-octanol, 2-octanol, 2-ethyl-1-hexanol, 1-nonanol, 1-decanol, 1-dodecanol, benzyl alcohol, cyclohexanol Shinnami Alcohol, phenol, α-methylbenzyl alcohol, more preferably methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, 2-butanol, isobutyl alcohol, 1-pentanol, 2-pentanol, 2 -Methyl-1-butanol, isopentyl alcohol, 3-methyl-2-butanol, 1-hexanol, 4-methyl-2-pentanol, 1-heptanol, 2-heptanol, 3-heptanol, 1-octanol, 2- Octanol, 2-ethyl-1-hexanol, 1-nonanol, 1-decanol, 1-dodecanol, benzyl alcohol, cyclohexanol, cinnamyl alcohol, phenol, α-methylbenzyl alcohol, more preferably methanol, ethanol Nord, 1-propanol, 2-propanol, 1-butanol, 2-butanol, isobutyl alcohol, 2-methyl-1-butanol, an isopentyl alcohol, most preferably ethanol.

  Examples of the divalent alcohol include 1,2-ethanediol, 1,2-propanediol, 1,3-propanediol, 1,2-butanediol, 1,3-butanediol, 1,4-butanediol, , 3-butanediol, 1,5-pentanediol and the like. 1,2-ethanediol, 1,2-propanediol, 1,3-butanediol and 1,3-propanediol are preferred, and 1,3-butanediol is most preferred.

  Glycerin or the like can be suitably used as the trivalent alcohol.

  The ketones are not particularly limited, regardless of whether they are cyclic or non-cyclic, and saturated or unsaturated. Specific examples include acetone, methyl ethyl ketone, methyl butyl ketone, methyl isobutyl ketone, acetophenone, 4-methoxyphenyl acetone, paramethyl acetophenone, methyl β-naphthyl ketone, and preferably acetone, acetophenone, 4-Methoxyphenylacetone, paramethylacetophenone, and methyl ethyl ketone, most preferably methyl ethyl ketone.

  The nitriles are not particularly limited regardless of whether they are cyclic or non-cyclic, and whether saturated or unsaturated. In general, saturated ones are preferably used. Usually, those having 2 to 20 carbon atoms, particularly 2 to 12 carbon atoms, especially 2 to 8 carbon atoms are preferably used. Specific examples include, for example, acetonitrile, propionitrile, malononitrile, butyronitrile, isobutyronitrile, succinonitrile, valeronitrile, glutaronitrile, hexanenitrile, heptyl cyanide, octyl cyanide, undecane nitrile, dodecane nitrile, tridecane Nitrile, pentadecane nitrile, stearonitrile, chloroacetonitrile, bromoacetonitrile, chloropropionitrile, bromopropionitrile, methoxyacetonitrile, methyl cyanoacetate, ethyl cyanoacetate, tolunitrile, benzonitrile, chlorobenzonitrile, bromobenzonitrile, cyano Benzoic acid, nitrobenzonitrile, anisonitrile, phthalonitrile, bromotolunitrile, methyl cyanobenzoate, methoxybenzene Zonitrile, acetylbenzonitrile, naphthonitrile, biphenylcarbonitrile, phenylpropionitrile, phenylbutyronitrile, methylphenylacetonitrile, diphenylacetonitrile, naphthylacetonitrile, nitrophenylacetonitrile, chlorobenzyl cyanide, cyclopropanecarbonitrile, cyclohexanecarbonitrile, Examples include cycloheptanecarbonitrile, phenylcyclohexanecarbonitrile, tolylcyclohexanecarbonitrile and the like.

  Preferred are acetonitrile, propionitrile, succinonitrile, butyronitrile, isobutyronitrile, valeronitrile, methyl cyanoacetate, ethyl cyanoacetate, benzonitrile, tolunitrile, chloropropionitrile, more preferably acetonitrile, Pionitrile, butyronitrile, isobutyronitrile, and most preferably acetonitrile.

  Examples of nitrogen compounds include nitromethane, triethylamine, pyridine, formamide, N-methylformamide, N, N-dimethylformamide, N, N-dimethylacetamide, N-methylpyrrolidone and the like in addition to the nitriles described above. Can do.

  Examples of sulfur compounds include dimethyl sulfoxide and sulfolane.

  Examples of the fatty acids include formic acid, acetic acid, propionic acid, butyric acid, valeric acid, caproic acid, enanthic acid, glycolic acid, lactic acid, tartronic acid, glyceric acid, hydroxybutyric acid, malic acid, tartaric acid, citramalic acid, and citric acid , Isocitric acid, leucine acid, mevalonic acid, pantoic acid, ricinoleic acid, ricinaleic acid, cerebronic acid, quinic acid, shikimic acid, gallic acid, ferulic acid, caffeic acid, chlorogenic acid, adipic acid, benzoic acid, gluconic acid, silicic acid Cinnamic acid, succinic acid, sorbic acid, nicotinic acid, parahydroxybenzoic acid, phenylacetic acid, pantothenic acid, fumaric acid, caprylic acid, capric acid, lauric acid, myristic acid, palmitic acid, stearic acid, isostearic acid, oleic acid, Linoleic acid, linolenic acid, arachidonic acid, behenic acid, eicosa Ntaenoic acid, docosahexaenoic acid and docosapentaenoic acid are preferred, and in particular, acetic acid, propionic acid, L-lactic acid, caprylic acid, lauric acid, oleic acid, linoleic acid, linolenic acid, and tartaric acid are preferred, and acetic acid, L- Lactic acid, caprylic acid and lauric acid are preferred, and L-lactic acid is most preferred.

  The fats and oils may be natural fats and oils from animals and plants, or synthetic fats and processed fats and oils. Examples of vegetable oils include 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, cottonseed oil, Sunflower seed oil, kapok oil, evening primrose oil, shea fat, monkey fat, cocoa butter, sesame oil, safflower oil, olive oil, avocado oil, poppy oil, burdock oil, etc. Pork fat, milk fat, fish oil, beef tallow, etc. can be mentioned, and furthermore, fats and oils processed by fractionation, hydrogenation, transesterification, etc. (for example, hardened oil) can also be mentioned. Needless to say, medium-chain fatty acid triglycerides (MCT), fatty acid partial glycerides and the like can also be used. Moreover, you may use these mixtures.

  Although it does not restrict | limit especially as medium chain fatty acid triglyceride, For example, the carbon number of a fatty acid is 6-12, respectively, Preferably 8-12 can be mentioned.

  Among the oils and fats, vegetable oils, synthetic oils and processed oils and fats are preferable from the viewpoints of easy handling and odor. Among these, specifically, palm oil, palm oil, palm kernel oil, rapeseed oil, rice oil, soybean oil, cottonseed oil, safflower oil, olive oil, medium chain fatty acid triglyceride (MCT), fatty acid partial triglycerides, and the like are preferable, Rice oil, soybean oil, rapeseed oil, safflower oil, medium chain fatty acid triglycerides, fatty acid partial triglycerides and the like are particularly preferred.

  Furthermore, in this invention, terpenes other than the specific terpenes mentioned above can also be used together. These terpenes are not particularly limited regardless of whether they are cyclic or non-cyclic, and saturated or unsaturated. Usually, hemiterpenes, monoterpenes, sesquiterpenes, diterpenes, triterpenes and the like can be mentioned.

  Specific examples include, for example, prenol, 3-methyl-3-buten-2-ol, tiglic acid, angelic acid, senecioic acid, isovaleric acid, allocymene, β-brubonene, δ-kadinene, dehydro-p-cymene, Menthol, dl-limonene, d-limonene, l-limonene, cis-3,7-dimethyl-1,3,6, -octatriene, δ-elemene, β-elemene, α-farnesene, β-farnesene, farnesene, Germaclen D, β-Guaien, Longifolene, β-Ocymene, α-Ferrandlene, Pinocamphone, Sabinen, Turpinolene, Tuopsen, α-Copaen, Hydrogenated Limonene Dimer, Isocalyophylene, Pinene Dimer, Dipentene Dimer, Dipentene Trimmer, Geraniol , Citral, citron Lahr, citronellol, 1,8-cineole, hydroxycitronellal, linalool, cosmene, nerol, myrsenol, lavandulol, ips edienol, neral, geranial, perylene, rose furan, geranilic acid, thioterpineol, α-terpineol, β-terpineol, γ-terpineol, δ-terpineol, carbeol, terpine, perylaldehyde, perilla alcohol, carvone, ascaridol, anethole, tsuyon, tuzanol, α-ionone, β-ionone, γ-ionone, farnesol, nerolidol , Α-sinensal, β-sinensal, bisabol, squalene, citronellioxyacetaldehyde, myrtenal, perilaaldehyde, 2-p-simenol, 2-ethoxy-p-cyno Men, carbenol, 4-carbomentenol, carbyl acetate, carbyl propionate, caryophyllene alcohol, caryophyllene acetate, 1,4-cineole, eugenol, d-selinen, thymol, d-camphene, linalool acetate, etc. .

  Preferably, prenol, 3-methyl-3-buten-2-ol, tiglic acid, angelic acid, senicioic acid, isovaleric acid, allocymene, β-brubonene, δ-kadinene, dehydro-p-cymene, dl-limonene, d-limonene, l-limonene, cis-3,7-dimethyl-1,3,6, -octatriene, δ-elemene, β-elemene, α-farnesene, β-farnesene, farnesene, germacrene D, β-guayene , Longifolene, β-cymene, α-ferrandrene, pinocamphone, sabinene, tsuyopsen, valencene, α-copaen, hydrogenated limonene dimer, isocalyophylene, pinene dimer, dipentene dimer, dipentene trimer, geraniol, citral, citronellal, citronellol 1 , 8-cineol, hydroxycitronellal, linalool, nerol, myrsenol, neral, geranial, carvone, anethole, thuyon, squalene, eugenol, d-selinen, thymol, linalool acetate, particularly preferably δ-casinene, α- Cariophyllene, dl-limonene, d-limonene, l-limonene, α-ferrandolene, geraniol, citral, citronellol, 1,8-cineole, linalool, carvone, anethole, tsuyon, eugenol, d-serinene, thymol, linalool acetate And most preferred are dl-limonene and d-limonene.

  Moreover, when using terpenes other than the specific terpenes mentioned above or specific terpenes, it can also be used as essential oil containing these. With respect to the essential oil, although not particularly limited, orange oil, capsicum oil, mustard oil, garlic oil, caraway oil, clove oil, cinnamon oil, cocoa extract, coffee bean extract, ginger oil, spearmint oil, celery seed oil, Thyme oil, onion oil, nutmeg oil, parsley seed oil, bran oil, vanilla extract, funnel oil, peni royal oil, paper mint oil, eucalyptus oil, lemon oil, rose oil, rosemary oil, almond oil, ajowan oil, Anise oil, Amiris oil, Angelica root oil, Ambrette seed oil, Estragon oil, Origanum oil, Oris root oil, Olivenum oil, Cassia oil, Cascarilla oil, Cananga oil, Chamomile oil, Calums oil, Cardamom oil, Carrot seed oil, Cubeb oil, cumin oil, grapefruit oil, cinnamon oil, cade oil, Soy sauce, Costas root oil, Cognac oil, Copaiba oil, Coriander oil, Perilla oil, Jasaki, Juniper berry oil, Star anise oil, Sage oil, Sevory oil, Geranium oil, Tangerine oil, Dill oil, Touka oil Oil, basil oil, birch oil, patchouli oil, palmarosa oil, pimento oil, petit grain oil, bay leaf oil, bergamot oil, peru balsam oil, benzoin resin, bored rose oil, hop oil, bologna absolute, marjolan oil, mandarin oil , Myrtle oil, yuzu fragrance, lime oil, lavender oil, lavender oil, roux oil, lemongrass oil, retionine, lobe oil, laurel leaf oil, wormwood oil and the like.

  Other solvents described above may also be used. In that case, a solvent acceptable for foods, pharmaceuticals, cosmetics and the like is preferable, and a solvent acceptable for foods is more preferable. From the viewpoint that the reaction product can be directly ingested without being processed, alcohols, fatty acids, water, fats and oils, terpenes other than specific terpenes or a mixture thereof are preferable. And their mixtures are more preferred, with oils and fats being most preferred.

In the production method of the present invention, a surfactant can be added to the reaction system during the reduction reaction, and it is often preferable to add it.
The surfactant is not particularly limited. For example, glycerin fatty acid ester, sucrose fatty acid ester, organic acid monoglyceride, sorbitan fatty acid ester, polyoxyethylene sorbitan fatty acid ester, propylene glycol fatty acid ester, polyglycerin condensed ricinoleic acid ester, Examples thereof include saponins and phospholipids.

  Although it does not restrict | limit especially as glycerol fatty acid ester, For example, the polymerization degree of glycerol can mention a 1-10 thing. Examples thereof include glycerin fatty acid esters having 6 to 18 carbon atoms in the fatty acid. Although it does not restrict | limit especially as a fatty acid residue which comprises glycerin fatty acid ester, The thing of carbon number of a fatty acid 6-18 can use each preferably, for example, caprylic acid, capric acid, lauric acid, myristic acid, palmitic acid Examples thereof include acids, stearic acid, isostearic acid, oleic acid, linoleic acid, and linolenic acid.

  The sucrose fatty acid ester is not particularly limited, and examples thereof include those in which a fatty acid having 6 to 22 carbon atoms is bonded to one or more hydroxyl groups of sucrose, such as sucrose laurate and sucrose myristine. Examples include acid esters, sucrose palmitate, sucrose stearate, sucrose oleate, sucrose behenate, and sucrose erucate.

  The organic acid monoglyceride is not particularly limited, but monoglycerol caprylic acid succinate, monoglycerol stearate citrate, monoglycerol stearate acetate, monoglycerol stearate succinate, monoglycerol stearate lactate, monoglycerol Examples thereof include stearic acid diacetyl tartaric acid ester and monoglycerin oleic acid citrate ester.

  The sorbitan fatty acid ester is not particularly limited, and examples thereof include those in which a fatty acid having 6 to 18 carbon atoms is bonded to one or more hydroxyl groups of sorbitan, such as sorbitan monolaurate, sorbitan monopalmitate, Examples include sorbitan monostearate and sorbitan monooleate.

  The polyoxyethylene sorbitan fatty acid ester is not particularly limited. For example, polyoxyethylene sorbitan monopalmitate, polyoxyethylene sorbitan monostearate, polyoxyethylene sorbitan monooleate having 6 to 20 moles of ethylene oxide chain added thereto. Examples thereof include esters, polyoxyethylene sorbitan tristearate, and polyoxyethylene sorbitan trioleate.

  As the propylene glycol fatty acid ester, any monoester or diester can be used. Although it does not restrict | limit especially as a fatty acid residue which comprises propylene glycol fatty acid ester, A C6-C18 fatty acid can be used preferably, for example, caprylic acid, capric acid, lauric acid, myristic acid, palmitic acid Examples thereof include acids, stearic acid, isostearic acid, oleic acid, linoleic acid, and linolenic acid.

  The polyglycerin condensed ricinoleic acid ester is not particularly limited. For example, the polyglycerin has an average degree of polymerization of 2 to 10 and an average degree of condensation of polyricinoleic acid (average number of condensed ricinoleic acids) of 2 to 4. Examples thereof include tetraglycerin condensed ricinoleic acid ester, pentaglycerin condensed ricinoleic acid ester, hexaglycerin condensed ricinoleic acid ester and the like.

  Although it does not restrict | limit especially as a saponin, Enju saponin, Kiraya saponin, refined soybean saponin, Yucca saponin, etc. can be mentioned.

  The phospholipid is not particularly limited.For example, egg yolk lecithin, purified soybean lecithin, phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, sphingomyelin, dicetylphosphate, stearylamine, phosphatidylglycerol, phosphatidic acid, phosphatidylinositolamine, cardiolipin, ceramide Examples include phosphorylethanolamine, ceramide phosphorylglycerol, and mixtures thereof. Needless to say, phospholipids subjected to processing such as hydrogenation and enzymatic degradation can also be used. From the viewpoint of improving the absorbability of reduced coenzyme Q10, it is preferable to use enzymatically decomposed phospholipids.

  The reducing agent used in the production method of the present invention is not particularly limited as long as it can convert oxidized coenzyme Q10 to reduced coenzyme Q10. For example, even if it is not common as a reducing agent, as long as it has the ability to convert oxidized coenzyme Q10 to reduced coenzyme Q10, naturally derived extracts such as extracts from animals and plants, pigments, animal and plant products, etc. Whether it is a component or a compound, it can be used as a reducing agent in the production method of the present invention.

  Examples of extracts from animals and plants that can be used as a reducing agent in the production method of the present invention include, for example, an acerola extract, a pine bark extract, a yellow leaf extract, a tea extract, a dokudami extract, an enzyme-treated rutin, and a red yeast rice extract. , Cranberry extract, rosemary extract, oolong tea extract, wild grape extract, maca extract, Indian date extract, etc., among them acerola extract, pine bark extract, twilight leaf extract, tea extract, A dokudami extract and an enzyme-treated rutin are preferable, and an acerola extract, a pine bark extract, a japonica leaf extract, and a tea extract are particularly preferable.

  Examples of animal and plant pigments that can be used as a reducing agent in the production method of the present invention include cacao pigments, gardenia pigments, grape skin pigments, and red grape pigments. Among these pigments, gardenia pigments are preferred.

  Examples of animal and plant products that can be used as a reducing agent in the production method of the present invention include royal jelly and perfume vinegar.

  Examples of the compound that can be used as the reducing agent in the production method of the present invention include L-ascorbic acid, D-arabo-ascorbic acid, L-ascorbyl palmitate, L-ascorbyl stearate, sodium borohydride, sodium hyposulfite, Retinal, β-carotene, tocotrienol, NADH, cyanocobalamin, octyl gallate, dodecyl gallate, sesamol, thiamine hydrochloride and the like, among which L-ascorbic acid, D-arabo-ascorbic acid, L-ascorbyl palmitate, L-ascorbyl stearate, sodium borohydride, sodium hyposulfite, retinal, β-carotene and tocotrienol are preferred, and L-ascorbic acid, D-arabo-ascorbic acid, L-ascorbyl palmitate, L-ascorbyl stearate are particularly preferred. , Sodium borohydride, sodium hydrosulfite, retinal is preferred.

  In the production method of the present invention, the reduction reaction may be carried out by coexisting raw material oxidized coenzyme Q10 and a reducing agent in the presence of the specific terpenes as necessary, and the method is not limited. In this case, coexistence means that the oxidized coenzyme Q10 as a raw material and the reducing agent are in contact with each other in the reaction system, and the system may be uniform or heterogeneous. Not limited. Of course, a system with high contact efficiency between oxidized coenzyme Q10 and a reducing agent is effective in reducing oxidized coenzyme Q10. From this viewpoint, oxidized coenzyme Q10 and reducing agent are in the same liquid phase. Is most preferably present.

  In the production method of the present invention, the weight ratio of the oxidized coenzyme Q10 and the reducing agent at the start of the reaction is not particularly limited, but usually the weight ratio of the reducing agent to the oxidized coenzyme Q10 (reducing agent / oxidized coenzyme). The enzyme Q10) is usually about 1/1000 or more, preferably about 1/100 or more, more preferably about 1/10 or more, and particularly preferably about 1/1 or more. The upper limit of the weight ratio of the reducing agent to oxidized coenzyme Q10 is not particularly limited, but is about 10,000 / 1 or less, preferably about 1000/1 or less, from the viewpoint of economy and effectiveness as a nutrient of the resulting composition. More preferably, it is about 100/1 or less, and particularly preferably about 10/1 or less.

  In the production method of the present invention, the concentration of oxidized coenzyme Q10 with respect to the reaction system (total weight of all reaction solutions) at the start of the reduction reaction is not particularly limited, but is usually about 0.01% by weight or more, preferably about 0%. 0.1% by weight or more, more preferably about 0.2% by weight or more, particularly preferably about 1% by weight or more, still more preferably about 2% by weight or more, especially about 3% by weight or more. The upper limit is not particularly limited, but is usually 99% by weight or less, preferably 98% by weight or less, and more preferably 96% by weight or less.

  The reaction temperature during the reduction reaction in the production method of the present invention is not particularly limited, but is usually 20 ° C. or higher, preferably 30 ° C. or higher, more preferably 40 ° C. or higher, more preferably 50 ° C. or higher, particularly preferably 60 ° C. That's it. Although an upper limit is not specifically limited, Usually, it is 200 degrees C or less, Preferably it is 150 degrees C or less, More preferably, it is 120 degrees C or less.

  In order to maximize the effects of the present invention, the reduction reaction is preferably performed, for example, in a deoxygenated atmosphere. The deoxygenated atmosphere can be achieved by substitution with an inert gas, reduced pressure, boiling, or a combination thereof. It is preferable to use at least substitution with an inert gas, that is, an inert gas atmosphere. Examples of the inert gas include nitrogen gas, helium gas, argon gas, hydrogen gas, carbon dioxide gas, and the like, preferably nitrogen gas.

  In the production method of the present invention, the reduction reaction can also be performed in the preparation. That is, after preparing a composition containing oxidized coenzyme Q10, a reducing agent, and the specific terpenes of the present invention, and processing the composition into a preparation form, oxidized coenzyme Q10 in the preparation of the form It is also within the scope of the present invention to produce reduced coenzyme Q10 by reducing the reduced coenzyme to reduced coenzyme Q10. The reduction in this case is performed by storage or heating for a certain period or longer. In the present invention, the formulation refers to oral administration forms such as capsules (hard capsules, soft capsules, microcapsules, etc.), tablets, syrups, beverages, etc., or forms such as creams, suppositories, and toothpastes. When the reduction reaction is performed in the preparation, the above-mentioned oral dosage form is preferable, more preferably a capsule, and particularly preferably a soft capsule.

  Reduced coenzyme Q10 can be easily produced by the production method of the present invention as described above. The proportion of reduced coenzyme Q10 in the total amount of coenzyme Q10 (ie, the total amount of reduced coenzyme Q10 and oxidized coenzyme Q10) at this time (at the end of the reaction) is usually about 65% by weight or more, preferably Is about 70% by weight or more, more preferably 85% by weight or more, particularly preferably 90% by weight or more, especially 95% by weight or more, especially 98% by weight or more.

Next, the composition and stabilization method of the present invention will be described.
The composition of the present invention comprises at least one terpene selected from the group consisting of p-cymene, α-pinene, valencene, myrcene, bisabolen, carene, caryophyllene, terpinene and phytol, reduced coenzyme Q10 and reducing agent. It is a composition containing this. The stabilization method of the present invention comprises a reducing agent in the presence of at least one terpene selected from the group consisting of p-cymene, α-pinene, valencene, myrcene, bisabolene, carene, caryophyllene, terpinene and phytol. This is a method for stabilizing reduced coenzyme Q10, characterized by coexisting reduced coenzyme Q10. That is, reduced coenzyme Q10 can be stabilized by using the composition of the present invention.

  In the composition and stabilization method of the present invention, the reduced coenzyme Q10 contained in the composition and to be stabilized is, for example, synthesized, fermented, extracted from natural products, or reduced oxidized coenzyme Q10. It can be obtained by a conventionally known method such as. Preferably, an oxidized coenzyme Q10 such as an existing high-purity coenzyme Q10, or a mixture of oxidized coenzyme Q10 and reduced coenzyme Q10 is used as a general reducing agent, for example, hydrosulfite sodium (sodium hyposulfite). , Obtained by reduction using sodium borohydride, ascorbic acid, etc., and more preferably oxidized coenzyme Q10 such as existing high purity coenzyme Q10, or oxidized coenzyme Q10 and reduced form It is obtained by reducing a mixture of coenzyme Q10 using ascorbic acids. Needless to say, reduced coenzyme Q10 obtained by the above-described production method of the present invention can also be suitably used.

  The reduced coenzyme Q10 used in the composition and stabilization method of the present invention may be reduced coenzyme Q10 alone or a mixture with oxidized coenzyme Q10. When the reduced coenzyme Q10 is a mixture with oxidized coenzyme Q10, the reduced coenzyme Q10 occupies the total amount of coenzyme Q10 (that is, the total amount of reduced coenzyme Q10 and oxidized coenzyme Q10). The ratio is not particularly limited, but is usually about 65% by weight or more, preferably about 70% by weight or more, more preferably 85% by weight or more, particularly preferably 90% by weight or more, especially 95% by weight or more, especially 98% by weight or more. It is. Although an upper limit is not specifically limited, Usually, it is 99.9 weight% or less.

  Specific examples and detailed description of the reducing agent used in the composition and stabilization method of the present invention are the same as those described in the production method of the present invention, and L-ascorbic acid, D-arabo-ascorbic acid, L-ascorbyl palmitate, L-ascorbyl stearate, sodium borohydride, sodium hyposulfite, retinal, acerola extract, pine bark extract, jade leaf extract, tea extract, gardenia pigment and the like can be used as more preferable examples. .

  In the composition and stabilization method of the present invention, the weight ratio of the reduced coenzyme Q10 and the reducing agent contained in the composition or used for stabilization is not particularly limited, but is usually reduced with respect to the reduced coenzyme Q10. The weight ratio of the agent (reducing agent / reduced coenzyme Q10) is usually about 1/1000 or more, preferably about 1/100 or more, more preferably about 1/10 or more, and particularly preferably about 1/1 or more. . The upper limit of the weight ratio of the reducing agent to reduced coenzyme Q10 is not particularly limited, but is about 10000/1 or less, preferably about 1000/1 or less, more preferably about 100/1 or less, particularly preferably about 10/1 or less. It is.

  In the composition and stabilization method of the present invention, a specific terpene capable of dissolving reduced coenzyme Q10 in a high concentration in the composition is used as a solvent. Terpenes used in the composition and stabilization method of the present invention are p-cymene, α-pinene, valencene, myrcene, bisabolen, karen, caryophyllene, turpinene, phytol, and mixtures thereof. From the viewpoint of solubility and stability of the reduced coenzyme Q10, p-cymene, α-pinene, valencene, myrcene, karen, caryophyllene, and tarpinene are more preferable, and in particular, p-cymene, valencene, myrcene, carene, and caryophyllene are preferable. Preferably, p-cymene and karen are most preferable.

  In addition, other solvents can be added to the above solvent as long as the solubility of reduced coenzyme Q10 and the oxidation of reduced coenzyme Q10 are not significantly adversely affected. Other solvents used in the composition and stabilization method of the present invention are not particularly limited, but hydrocarbons, fatty acid esters, ethers, alcohols, ketones, fatty acids, ketones, nitrogen compounds ( Nitriles and amides), organic solvents such as sulfur compounds, oils and fats, water and the like. Specific examples and detailed descriptions of other solvents that can be used in the composition and stabilization method of the present invention are the same as those described in the production method of the present invention, and alcohols, fatty acids, water, fats and oils, specific The terpenes other than the terpenes or a mixture thereof are preferable, more preferably an oil or fat, or an oil and a mixture thereof, and most preferably an oil or fat.

  Also in the composition and stabilization method of the present invention, a surfactant can be added as well as the production method of the present invention, and it is often preferable to add a surfactant. In the composition and stabilization method of the present invention, the detailed types and preferred examples of the surfactant used are the same as those described in the production method of the present invention.

  In the composition and the stabilization method of the present invention, the reduced coenzyme Q10 and the reducing agent coexist in the composition in the presence of the specific terpenes. Should be in some form of contact. The contact form is not particularly limited, and the composition system may be uniform or heterogeneous, but a system with high contact efficiency between reduced coenzyme Q10 and the reducing agent is reduced. It is effective for stabilizing the coenzyme Q10, and it is most preferable that the reduced coenzyme Q10 and the reducing agent exist in the same liquid phase.

  In the composition and stabilization method of the present invention, reduced coenzyme Q10 and reducing agent, specific terpenes, other solvents, and substances other than surfactants include, for example, excipients, disintegrants, lubricants. Agents, binders, dyes, aggregation inhibitors, absorption promoters, solubilizers, stabilizers, active ingredients other than reduced coenzyme Q10, and the like can be included, and are not particularly limited.

  The excipient is not particularly limited, and examples thereof include sucrose, lactose, glucose, starch, mannitol, crystalline cellulose, calcium phosphate, calcium sulfate and the like.

  The disintegrant is not particularly limited, and examples thereof include starch, agar, calcium citrate, calcium carbonate, crystalline cellulose, carboxymethyl cellulose, tragacanth, and alginic acid.

  The lubricant is not particularly limited, and examples thereof include talc, magnesium stearate, polyethylene glycol, silica, and hardened oil.

  The binder is not particularly limited, and examples thereof include ethyl cellulose, methyl cellulose, hydroxypropyl methyl cellulose, hydroxypropyl cellulose, tragacanth, shellac, gelatin, pullulan, gum arabic, polyvinyl pyrrolidone, polyvinyl alcohol, polyacrylic acid, polymethacrylic acid, And sorbitol.

  Although it does not restrict | limit especially as said pigment | dye, For example, pigment | dyes, such as a titanium oxide, a synthetic pigment | dye, a bengara pigment | dye, a tar pigment | dye, can be mentioned.

  The aggregation preventing agent is not particularly limited, and examples thereof include stearic acid, talc, light anhydrous silicic acid, hydrous silicic acid dioxide and the like.

  The absorption promoter is not particularly limited, and examples thereof include higher alcohols and higher fatty acids.

  The dissolution aid is not particularly limited, and examples thereof include organic acids such as fumaric acid and succinic acid.

  Although it does not restrict | limit especially as said stabilizer, For example, benzoic acid, beeswax, hydroxypropyl methylcellulose, methylcellulose etc. can be mentioned.

  The active ingredient other than the reduced coenzyme Q10 is not particularly limited. For example, amino acids, vitamins such as vitamin C and vitamin E and derivatives thereof, carotenoids such as β-carotene and astaxanthin, minerals, polyphenols, Organic acids, saccharides, peptides, proteins and the like can be mentioned.

  The above substances may play a plurality of roles. For example, starch may serve as an excipient and a disintegrant.

  In the composition and the stabilization method of the present invention, the content of the reducing agent relative to the total weight of the composition is not particularly limited, but from the viewpoint of sufficiently exhibiting the stabilizing effect of the reduced coenzyme Q10, the total weight of the composition. The ratio to the above is usually about 0.01% by weight or more, preferably about 0.1% by weight or more, more preferably about 1% by weight or more, and particularly preferably about 10% by weight or more.

  In the composition and stabilization method of the present invention, the content of reduced coenzyme Q10 with respect to the total weight of the composition is not particularly limited, but is usually about 10% by weight or more from the viewpoint of preparing a high-concentration solution composition. Preferably it is about 20% by weight or more, more preferably about 23% by weight or more, further preferably 25% by weight or more, particularly preferably 30% by weight or more, particularly preferably 35% by weight or more, especially 40% by weight or more.

  In the composition and stabilization method of the present invention, the method for preparing a composition containing reduced coenzyme Q10, a reducing agent, and specific terpenes is not particularly limited. For example, when using externally added reduced coenzyme Q10, the reduced coenzyme Q10, a reducing agent, and a specific terpene may be simply mixed, and after mixing these, other solvents as described above may be used. And other components may be further mixed. Further, a reducing agent and other components may be mixed in a solution obtained by dissolving reduced coenzyme Q10 in a specific terpene.

  Alternatively, the reduced coenzyme Q10 obtained by the production method of the present invention is used as it is, that is, a mixture in which the reduced coenzyme Q10 and the reducing agent after the reduction reaction coexist in a specific terpene, It can be used as it is as a composition in the present invention, and this embodiment is one of the most preferred embodiments.

  Since the composition of the present invention was also invented based on the fact that the terpenes can dissolve reduced coenzyme Q10 at a high concentration, at least the reduced coenzyme Q10 has a high concentration in the terpenes. Compositions contained in a dissolved state are also within the scope of the present invention. Specifically, 25% by weight or more of reduced coenzyme Q10 in at least one terpene selected from the group consisting of p-cymene, α-pinene, valencene, myrcene, bisabolen, carene, caryophyllene, terpinene and phytol. The liquid composition to be contained is also an embodiment of the present invention. The content of reduced coenzyme Q10 contained in the terpene is not particularly limited as long as it is 25% by weight or more, but is preferably 27% by weight or more, more preferably 30% by weight or more, and particularly preferably 33% by weight or more. preferable. In the composition, as described in the composition of the present invention, other solvents other than the specific terpenes, surfactant, excipient, disintegrant, lubricant, binder, dye, aggregation An inhibitor, absorption promoter, solubilizer, stabilizer, active ingredient other than reduced coenzyme Q10, and the like can also be contained. Specific examples and preferred examples thereof are the same as those described in the composition of the present invention. The composition can be obtained, for example, by removing the used reducing agent from the reaction product obtained by the production method of the present invention, if necessary, or by the production method of the present invention. The obtained reduced coenzyme Q10 can also be obtained by dissolving in the terpenes after isolation.

  In order to maximize the effects of the present invention, it is preferable to carry out the stabilization method of the present invention in a deoxygenated atmosphere, that is, to perform the above-mentioned coexistence. It is preferably prepared and / or stored below. Moreover, it is preferable to perform the process to the formulation mentioned later and the preservation | save after a process in a deoxygenated atmosphere. The deoxygenated atmosphere can be achieved by substitution with an inert gas, reduced pressure, boiling, or a combination thereof. It is preferable to use at least substitution with an inert gas, that is, an inert gas atmosphere. Examples of the inert gas include nitrogen gas, helium gas, argon gas, hydrogen gas, carbon dioxide gas, and the like, preferably nitrogen gas.

  Although the composition of the present invention can be used as it is, it is a preparation as described in the production method of the present invention, that is, oral administration forms such as capsules (hard capsules, soft capsules, microcapsules), tablets, syrups, beverages and the like. It can also be used by processing into forms for creams, suppositories, toothpastes and the like. Among them, it is preferable to process into the above oral dosage form, particularly preferably in the form of a capsule, and particularly preferably in the form of a soft capsule. At this time, the capsule base material is not particularly limited, and includes other base materials (for example, carrageenan that can be used as a food additive, Materials for production containing thickening stabilizers and celluloses such as seaweed-derived products such as alginic acid and plant seed-derived products such as locust bean gum and guar gum can also be used.

  The composition of the present invention not only has the reduced coenzyme Q10, which is an active ingredient, protected from oxidation and is stably retained, but also contains a high concentration preparation of reduced coenzyme Q10 by using specific terpenes. In addition, other ingredients that are effective as nutrients are also included, so a synergistic effect with reduced coenzyme Q10 can be expected, and foods and supplements such as nutritional functional foods and foods for specified health use, drinks, pharmaceuticals, animals It can also be a composition useful as a medicine, cosmetics, pet food or the like.

EXAMPLES Hereinafter, the present invention will be described in more detail with reference to examples, but the present invention is not limited only to these examples. Further, the purity of reduced coenzyme Q10 in the examples and the weight ratio of reduced coenzyme Q10 to oxidized coenzyme Q10 were determined by the following HPLC analysis. The purity of reduced coenzyme Q10 obtained was as follows. The limit value of purity in the present invention is not specified, and similarly, the weight ratio of reduced coenzyme Q10 and oxidized coenzyme Q10 does not specify the upper limit value. In this example, the weight ratio of reduced coenzyme Q10 and oxidized coenzyme Q10 is simply expressed, so that it accounts for the total amount of coenzyme Q10 (total amount of oxidized coenzyme Q10 and reduced coenzyme Q10). The ratio of reduced coenzyme Q10 is expressed as a percentage as “weight ratio of reduced coenzyme Q10”. For example, when “weight ratio of reduced coenzyme Q10 is 20%”, it means that the weight ratio of reduced coenzyme Q10 and oxidized coenzyme Q10 is 20/80.

(HPLC analysis conditions)
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 ml / Min, retention time of reduced coenzyme Q10; 9.1 min, retention time of oxidized coenzyme Q10; 13.3 min.

Example 1
3 g of each of the terpenes listed in Table 1 (p-cymene, α-pinene, valencene, myrcene, bisabolene, caren, caryophyllene, terpinene) was added to a 25 ml test tube, and reduced coenzyme Q10 (purity: 99) 0.5 wt.%) Was added, and the inside of the container was purged with nitrogen, followed by stirring and holding at 60 ° C. for 1 hour to obtain a uniform solution. This solution was cooled to 25 ° C. and then stirred for 16 hours to obtain a slurry in which partially reduced coenzyme Q10 was deposited. The resulting slurry was filtered to separate only the solution portion, and the reduced coenzyme Q10 concentration in this solution was determined by analysis. The obtained analysis results are shown in Table 1. Table 1 also shows the solubility of limonene as an object.

(Example 2)
Terpenes listed in Table 2 (p-cymene, α-pinene, valencene, myrcene, bisabolene, carene, caryophyllene, terpinene, phytol) each 3 g, oxidized coenzyme Q10 crystals 0.2 g (0.23 mmol), 6 equivalents (576 mg, 1.39 mmol) of L-ascorbyl palmitate was added, and the inside of the container was purged with nitrogen, followed by stirring at 80 ° C. for 16 hours. Table 2 shows the weight ratio of reduced coenzyme Q10 in the reaction solution after the reaction. Table 2 also shows the results when limonene was used as a solvent as a target.

(Example 3)
Terpenes listed in Table 3 (valencene, myrcene, bisabolen, caryophyllene, terpinene, phytol) each 3 g, 0.2 g (0.23 mmol) of oxidized coenzyme Q10 crystals and 6 equivalents of L-ascorbic acid (245 mg, 1 .39 mmol) was added and the atmosphere in the container was replaced with nitrogen, followed by stirring at 80 ° C. for 16 hours. Table 3 shows the weight ratio of reduced coenzyme Q10 in the reaction solution after the reaction. Table 3 also shows the results when limonene was used as a solvent as a target.

Example 4
After adding 0.3 g of distilled water to 3 g of each of the terpenes listed in Table 4 (p-cymene, α-pinene, valencene, myrcene, bisabolene, carene, caryophyllene, turpinene, phytol), oxidized coenzyme Q10 crystal 0 0.2 g (0.23 mmol) and 6 equivalents of L-ascorbyl palmitate (576 mg, 1.39 mmol) were added, and the atmosphere in the vessel was replaced with nitrogen, followed by stirring at 80 ° C. for 16 hours. Table 4 shows the weight ratio of reduced coenzyme Q10 in the reaction solution after the reaction. Table 4 also shows the results when limonene was used as a solvent as a target.

(Example 5)
After adding 3 g of acetic acid to 3 g of each of the terpenes listed in Table 5 (valensen, myrcene, bisabolen, caryophyllene, terpinene, phytol), 0.2 g (0.23 mmol) of oxidized coenzyme Q10 crystals and L-ascorbic acid 6 equivalents (245 mg, 1.39 mmol) were added, and the atmosphere in the container was replaced with nitrogen, followed by stirring at 80 ° C. for 16 hours. Table 5 shows the weight ratio of reduced coenzyme Q10 in the reaction solution after the reaction. Table 5 also shows the results when limonene was used as a solvent as a target.

(Example 6)
After adding 20 kg (23.2 mol) of oxidized coenzyme Q10 crystals and 1.8 equivalents (17.3 kg, 41.8 mol) of L-ascorbyl palmitate to 26.8 kg of Karen, the inside of the reaction vessel was purged with nitrogen , And stirred at 80 ° C. for 24 hours. A gelatin soft capsule preparation using the composition obtained after the reaction as it was as it was was prepared by a conventional method.

(Example 7)
The composition containing reduced coenzyme Q10 after the reaction obtained in Examples 2 to 5 and the reducing agent and the gelatin soft capsule prepared in Example 6 were each stored in air at 25 ° C. for 1 week. The weight ratio of reduced coenzyme Q10 after storage was not lower than the value at the start of storage.

Claims (9)

p- cymene, and features Varensen, myrcene, carene, the presence of at least one terpene selected from the group consisting of caryophyllene 及 beauty phytol, to reduce the oxidized coenzyme Q10 using L- ascorbyl palmitate To produce reduced coenzyme Q10. The production method according to claim 1 , wherein an organic solvent, fats and oils, water, or a mixture thereof is further allowed to coexist during the reduction reaction. The production method according to claim 2 , wherein the organic solvent is an alcohol and / or a fatty acid. Fats and oils are palm oil, palm oil, palm kernel oil, linseed oil, camellia oil, brown rice germ oil, olive oil, rapeseed oil, rice oil, peanut oil, corn oil, wheat germ oil, soybean oil, sesame oil, cottonseed oil, sunflower seeds Oil, kapok oil, evening primrose oil, shea fat, monkey fat, cocoa butter, sesame oil, safflower oil, avocado oil, poppy oil, burdock oil, pork fat, milk fat, fish oil, beef tallow, fractionated, hydrogenated, ester The production method according to claim 2 , which is at least one selected from the group consisting of fats and oils processed by exchange, medium-chain fatty acid triglycerides, and partial glycerides of fatty acids. The production method according to any one of claims 1 to 4 , wherein the concentration of oxidized coenzyme Q10 in the reaction system at the start of the reduction reaction is 0.01 wt% or more. The manufacturing method of any one of Claims 1-5 which implements a reductive reaction in a formulation. The production method according to claim 6 , wherein the preparation is a capsule. The manufacturing method according to claim 7 , wherein the capsule is a soft capsule. The process according to any one of claims 1 to 8 for reduction in deoxidized atmosphere.