WO2007126083A1 - 還元型補酵素q10の安定化方法 - Google Patents
還元型補酵素q10の安定化方法 Download PDFInfo
- Publication number
- WO2007126083A1 WO2007126083A1 PCT/JP2007/059252 JP2007059252W WO2007126083A1 WO 2007126083 A1 WO2007126083 A1 WO 2007126083A1 JP 2007059252 W JP2007059252 W JP 2007059252W WO 2007126083 A1 WO2007126083 A1 WO 2007126083A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- reduced coenzyme
- coenzyme
- reduced
- weight
- oxidized
- Prior art date
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C41/00—Preparation of ethers; Preparation of compounds having groups, groups or groups
- C07C41/01—Preparation of ethers
- C07C41/34—Separation; Purification; Stabilisation; Use of additives
- C07C41/46—Use of additives, e.g. for stabilisation
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
- A61K31/047—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates having two or more hydroxy groups, e.g. sorbitol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
- A61K8/35—Ketones, e.g. benzophenone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4858—Organic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/02—Nutrients, e.g. vitamins, minerals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
- A61P39/06—Free radical scavengers or antioxidants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
Definitions
- the present invention relates to a method for stabilizing reduced coenzyme Q, and a reduced coenzyme that is stable against oxidation.
- Reduced coenzyme Q is a conventionally known method such as synthesis, fermentation, extraction from natural products, etc.
- Patent Document 1 the reduced coenzyme Q
- Patent Document 5 describing a composition in which a reducing agent coexists and a method for producing the same, (1) reduced coenzyme Q;
- a composition comprising 10 and an effective amount of a surfactant, plant oil or mixture thereof for dissolving the reducing agent; and optionally a solvent; (2) the composition is a gelatin capsule or tablet In addition, it is formulated into an oral preparation for oral administration, and (3) contains reduced coenzyme Q in situ using oxidized coenzyme Q and a reducing agent.
- a method for preparing the above composition is disclosed, but reduced coenzyme Q contained in the composition is disclosed.
- composition and the preparation method thereof have multiple roles in the composition (that is, first, oxidized coenzyme Q is reduced to reduced coenzyme Q.
- the reaction mixture is used as it is, so it is not necessarily safe. That is, ascorbic acid used as a reducing agent is oxidized to produce a considerable amount of dehydroascorbic acid, which is problematic when mixed in the composition. Unlike ascorbic acid, dehydroascorbic acid and oxalic acid produced by its decomposition are highly harmful. For example, an increase in the amount of lipid peroxide in the liver and kidney, a decrease in antioxidants, and an increase in the amount of oxalic acid in the kidney have been reported, leading to decreased resistance to oxidative stress and ureteral stones. There are concerns about side effects such as ⁇ (Non-patent Document 1).
- Patent Document 1 JP-A-10-109933
- Patent Document 2 WO03Z06408 pamphlet
- Patent Document 3 WO03Z06409 pamphlet
- Patent Document 4 Pamphlet of WO03Z32967
- Patent Document 5 WOOOlZ52822 pamphlet
- Non-Patent Document 1 -Nutrition Research 13 ⁇ , 667-676, 1993
- the present invention provides a food containing reduced coenzyme Q, a nutritional functional food, a specific food
- An object is to provide a simple and suitable method and composition for protecting and maintaining stable.
- reduced coenzyme Q is reduced relative to reduced coenzyme Q without adding a reducing agent.
- the present invention was completed by finding that 6% by weight or more and coexistence of Z or reduced coenzyme Q11 can protect reduced coenzyme Q10 from oxidation and keep it stable.
- the present invention is as follows.
- the reduced coenzyme Q is characterized by the coexistence of the following (a) and Z or (b):
- the reduced coenzyme Q is an active ingredient and is administered to mammals [6] or [11]
- composition according to [6] or [7] comprising at least one selected from group power consisting of other active ingredients other than 10.
- [13] The composition according to [12], which is a capsule.
- Capsule strength The composition according to [13], which is a microcapsule, a soft capsule or a hard capsule.
- a process comprising the steps of (a) and Z or (b) being separately prepared and added:
- a production method comprising a step of reducing oxidized coenzyme Q10, including oxidized coenzyme Q11:
- reduced coenzyme Q and reduced coenzyme Q are the same as reduced coenzyme Q in vivo.
- More effective coenzyme Q can be achieved compared to the composition. Furthermore, the reduced coenzyme Q 9 can be absorbed in vivo by reducing coenzyme.
- composition in which reduced coenzyme Q 9 and reduced coenzyme Q 10 coexist can provide a composition having enhanced absorbability as the total amount of coenzyme Q.
- FIG. 1 is a graph showing the measurement results of total coenzyme Q concentration in each plasma of reduced coenzyme Q9-administered rats and reduced coenzyme Q10-administered rats.
- FIG. 2 shows reduced coenzyme Q administered rats, reduced coenzyme Q and reduced coenzyme Q.
- FIG. 10 is a graph showing the measurement results of coenzyme Q 10 concentration in each plasma for rats administered with 10 10 11 mixture.
- the reduced coenzyme Q may contain oxidized coenzyme Q.
- the ratio of 10 is not particularly limited
- 20% by weight or more usually 40% by weight or more, preferably 60% by weight or more, more preferably 80% by weight or more, especially 90% by weight or more, especially 96% by weight or more.
- the upper limit is 100% by weight and is not particularly limited, but it is usually 99.9% by weight or less.
- Reduced coenzyme Q can be obtained by various methods as described above, for example, WO
- the reduced coenzyme Q stability method of the present invention (hereinafter also referred to as the stability method of the present invention) is:
- 11 is a method characterized by the coexistence of 11 and the reduced coenzyme Q by molecular oxygen.
- the amount of 11 is not particularly limited, but reduced coenzyme Q
- 10 is usually about 0.1% by weight or more.
- the upper limit of the amount of 11 is not particularly limited, but is usually about 99% by weight or less, preferably about 90% by weight or less, more preferably about 80% by weight or less, particularly preferably about 70% by weight or less, and more preferably about 60% or less, especially about 50% or less, especially about 40% or less. Needless to say, both reduced coenzyme Q and reduced coenzyme Q are included in reduced coenzyme Q.
- (a) and Z or (b) may be prepared separately.
- the above-mentioned prepared products are obtained, for example, by extracting and purifying natural products.
- Oxidized coenzyme Q and oxidized coenzyme Q were prepared by the above-mentioned WO03Z06408 pamphlet.
- the stabilization method of the present invention comprises oxidized coenzyme Q and
- composition of the present invention is:
- Suitable amounts of reduced coenzyme Q 9 and Z or reduced coenzyme Q 11 contained in reduced coenzyme Q 10 are as described above.
- Reduced coenzyme Q 9 and Z or reduced coenzyme Q 11 separately added to reduced coenzyme Q 10 may be added as the composition of the present invention, or oxidized coenzyme Q 9 and / or The composition of the present invention may be obtained by reducing oxidized coenzyme Q10 containing oxidized coenzyme Q11.
- a manufacturing method comprising a step in which (a) and Z or (b) are separately prepared and added.
- the production method of reduced coenzyme Q 10 containing reduced coenzyme Q 9 and Z or reduced coenzyme Q 11 is not particularly limited!
- the process in which (a) and Z or (b) are separately prepared and added is the process of adding (a) and Z or (b) separately prepared as described above.
- the koji is performed by a known method.
- the oxidized coenzyme Q is 0.6% by weight with respect to the oxidized coenzyme Q.
- Oxidized coenzyme Q including 11
- This method includes the process of reducing 10. Reduced coenzyme Q in which (a) and Z or (b) coexist in the final step
- the method of adding 11 can be used in combination.
- the form of the 10-containing composition is not particularly limited, and is in a crystalline form; dissolved or suspended in a solvent; melted form maintained above the melting point; or administered to mammals such as oral or topical preparations Even if it is a deviation of the form intended.
- the form in which 11 is contacted is not particularly limited.
- reduced coenzyme Q 9 and Z or reduced coenzyme Q 11 may be dissolved in the melt of reduced coenzyme Q 10.
- the solvent that can be used in the present invention is not particularly limited, and includes hydrocarbons, fatty acid esters, ethers, alcohols, fatty acids, ketones, nitrogen compounds (nitriles, amides). ), Sulfur compounds, oils and fats, water and the like. These solvents can also be used as a mixture of any two or more.
- Hydrocarbons are not particularly limited, and examples thereof include aliphatic hydrocarbons, aromatic hydrocarbons, and halogenated hydrocarbons. In particular, aliphatic hydrocarbons and aromatic hydrocarbons are preferred, and aliphatic hydrocarbons are particularly preferred.
- the aliphatic hydrocarbon is not particularly limited regardless of whether it is cyclic or non-cyclic, or saturated or unsaturated, but saturated hydrocarbons are generally preferably used. Usually, those having 3 to 20 carbon atoms, particularly 5 to 12 carbon atoms, especially 5 to 8 carbon atoms are preferably used.
- pentane, 2-methylbutane, hexane, 2-methylpentane, 2,2-dimethylbutane, 2,3-dimethylbutane, heptane, heptane isomers for example, 2-methylhexane, 3 —Methylhexane, 2,3-dimethylpentane, 2,4-dimethylpentane), octane, 2, 2,3-trimethylpentane, isooctane, nonane, 2, 2,5-trimethylhexane, decane, dodecane, Cyclopentane, methylcyclopentane, cyclohexane, methylcyclohexane, ethylcyclohexane, p-menthane, etc.
- pentane 2-methylbutane, hexane, 2-methylpentane, 2, 2-dimethylbutane.
- 2,3-dimethylbutane, heptane, heptane isomers eg, 2-methylhexane, 3-methylhexane, 2,3-dimethylpentene Emissions, 2, 4-dimethyl pentane
- octane 2, 2, 3-trimethyl Chirupentan, isooctane, cyclopentane, methylcyclopentane, cyclohexane, hexane main Chirushikuro, cyclohexane and the like Echirushikuro is preferable.
- heptanes and heptanes are preferably used.
- pentane having 5 carbon atoms eg, pentane
- hexanes having 6 carbons eg, hexane, cyclohexane, etc.
- heptanes having 7 carbon atoms eg, heptane, methylcyclohexane, etc.
- the most preferable is a heptane (for example, heptane, methylcyclohexane, etc.), and heptane is particularly preferable.
- the aromatic hydrocarbon is not particularly limited, but usually, an aromatic hydrocarbon having 6 to 20 carbon atoms, particularly 6 to 12 carbon atoms, especially 7 to 10 carbon atoms is preferably used.
- Specific examples include, for example, benzene, toluene, xylene, o-xylene, m-xylene, p-xylene, ethyl benzene, tamen, mesitylene, tetralin, butylbenzene, p-cymene, cyclohexyl.
- Examples include benzene, jetylbenzene, pentylbenzene, dipentylbenzene, dodecylbenzene, and styrene.
- Toluene, xylene, o-xylene, m-xylene, p-xylene, ethylbenzene, tamen, mesitylene, tetralin, butylbenzene, p-cymene, cyclohexylbenzene, jetylbenzene, pentylbenzene, etc. are preferred, especially toluene, xylene, o Xylene, m-xylene, p-xylene, cumene, tetralin and the like are preferable. Most preferred is cumene.
- the halogenated hydrocarbon is not particularly limited regardless of whether it is cyclic or non-cyclic, or saturated or unsaturated, but generally a non-cyclic hydrocarbon is preferably used. Usually, chlorinated hydrocarbons and fluorinated hydrocarbons are preferred, and chlorinated hydrocarbons are particularly preferred. Those having 1 to 6 carbon atoms, particularly 1 to 4 carbon atoms, especially 1 to 2 carbon atoms are preferably used.
- Examples include, for example, dichloromethane, chlorophenol, carbon tetrachloride, 1,1-dichloroethane, 1,2-dichlorodiethane, 1,1,1-trichlorodiethane, 1,1,2-trichlorodiethane, 1,1,1,2-tetrachloroethane, 1,1,2,2-tetrachloroethane, pentachloroethane, hexachloroethane, 1,1-dichloroethylene, 1,2-dichloroethylene, Examples include trichloroethylene, tetrachloroethylene, 1,2 dichloropronone, 1,2,3 trichloropronone, chlorobenzene, 1,1,1,2-tetrafluoroethane.
- dichloromethane, black mouth form, carbon tetrachloride, 1, 1-dichloroethane, 1, 2-dichloro mouth ethane, 1, 1, 1 trichloro mouth ethane, 1, 1, 2-triclo mouth ethane, 1,1-dichloroethylene, 1,2-dichloroethylene, trichloroethylene, black benzene, 1,1,1,2-tetrafluoroethane, etc. are preferred, especially dichloromethane, black mouth form, 1,2-dichloroethylene , Trichloroethylene, black-opened benzene, 1,1,1,2-tetrafunoleethane and the like are preferable.
- the fatty acid esters are not particularly limited, and examples thereof include propionic acid esters, acetic acid esters, formic acid esters and the like. In particular, acetates and ester formate are preferred, and acetates are particularly preferred.
- the ester group includes an alkyl ester or aralkyl ester having 1 to 8 carbon atoms, preferably an alkyl ester having 1 to 6 carbon atoms, more preferably an alkyl ester having 1 to 4 carbon atoms. Tell is preferably used.
- propionic acid ester examples include, for example, methyl propionate, ethyl propionate, butyl propionate, and isopentyl propionate.
- acetate examples include, for example, methyl acetate, ethyl acetate, propyl acetate, isopropyl acetate, butyl acetate, isobutyl acetate, sec-butyl acetate, pentyl acetate, isopentyl acetate, sec-hexyl acetate, and cyclohexane acetate. Examples include hexyl, benzyl acetate and the like.
- Methyl acetate, ethyl acetate, propyl acetate, isopropyl acetate, butyl acetate, isobutyl acetate, sec-butyl acetate, pentyl acetate, isopentyl acetate, sec-hexyl acetate, cyclohexyl acetate and the like are preferable. More preferred are methyl acetate, ethyl acetate, propyl acetate, isopropyl acetate, butyl acetate, isobutyl acetate and the like, with ethyl acetate being particularly preferred.
- formate ester examples include methyl formate, ethyl formate, propyl formate, isopropyl formate, butyl formate, isobutyl formate, sec-butyl formate, pentyl formate and the like. Methyl formate, ethyl formate, propyl formate, butyl formate, isobutyl formate, pentyl formate and the like are preferred. More preferred is ethyl formate.
- the ethers are not particularly limited regardless of whether they are cyclic or non-cyclic, and saturated or unsaturated, but saturated ethers are generally preferably used. Usually, those having 3 to 20 carbon atoms, especially 4 to 12 carbon atoms, especially 4 to 8 carbon atoms are preferably used.
- Specific examples include, for example, jetinoreethenore, methinore tert-butinoreethenore, dipropinoreethenore, diisopropinoreethenore, dibutinoreethenore, dihexinoreethenore, ethinorevininore 1 Tenoré, Butinolevinoleate eclectic, Anisolinore, Feneto Monore, Butinoleuenoreatenore, Methoxytoluene, Dioxane, Furan, 2-Methylfuran, Tetrahydrofuran, Tetrahydropyran, Ethylene glycol dimethyl ether, Ethylene glycol genyl Examples include ether, ethylene glyconoresino chinenoate, ethylene glycol monomethino enoate, ethylene glycol eno enoenoate, ethylene glycono lesino chinenoate, and
- jetyl ether methyl tert-butyl ether, dipropyl ether, diisopropyl ether, dibutyl ether, dihexyl ether, anisole, phenetole, butyl phenyl ether, methoxytoluene, dioxane, 2-methyl furan , Tetrahydrofuran, tetrahydropyran, ethylene glycol dimethyl ether, ethylene glycol dimethyl ether, ethylene glycol resin butyl enoate ether, ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, etc.
- jetyl ether especially jetyl ether, methyl tert —Butyl ether, carbole, dioxane, tetrahydrofuran, ethylene glycol monomethyl ether ether, ethylene glycol methanol ether, etc. are preferred. Most preferred are jetyl ether, methyl tert-butyl ether, anisole, dioxane, tetrahydrofuran and the like, with dioxan and tetrahydrofuran being particularly preferred.
- 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, propio-tolyl, malono-tolyl, petit nitrinole, isobutyronitrile, succinonitrile, norronitrinol, gnoletaronitrile, hexan-tolyl, heptylcia.
- the alcohol is not particularly limited regardless of whether it is cyclic or non-cyclic, and whether saturated or unsaturated.
- a saturated alcohol is preferably used.
- dihydric alcohols having 2 to 5 carbon atoms, and trivalent alcohols having 3 carbon atoms are preferred.
- these alcohols include, for example, 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 monohexanol, 2-methyl 1 pentanol, 4-methyl-2 pentanol, 2 ethyl 1-butanol, 1 1-Heptanol, 2-Heptanol, 3-Heptanol, 1-octanol, 2 Otanol, 2-Ethyl-1-hexanol, 1-Nonanol, 1-decanol, 1-undeol, 1 Dodecanol, Arryl alcohol, Propargil Arco , Benzylamine
- Examples of the monohydric alcohol include methanol, ethanol, 1 propanol, 2 propanol, 1-butanol, 2-butanol, isobutyl alcohol, and tert butyl alcohol.
- Dihydric alcohols include 1,2 ethanediol, 1,2 propanediol, 1,3-propanediol, 2-butene 1,4-diol, 2-methyl-2,4-pentanediol, and 2-ethyl-1,3-hexanediol.
- 1,2-propanediol, polyethylene glycol, etc. are preferred, such as diethylene glycol, triethylene glycolone, tetraethylenedarlicol, polyethylene glycol, dipropylene glycolol, and polypropylene glycol. Is most preferred.
- the trihydric alcohol glycerin is preferable.
- ketones are not particularly limited, and those having 3 to 6 carbon atoms are preferably used.
- acetone particularly preferred is acetone.
- nitrogen compounds include nitromethane, acetonitrile, triethylamine, pyridine, formamide, N-methylformamide, N, N-dimethylformamide, N, N-dimethylacetamide, N-methylpyrrolidone and the like. Acetonitrile is particularly preferred.
- sulfur compounds include dimethyl sulfoxide, sulfolane and the like.
- Dimethyl sulfoxide is preferred.
- fatty acids examples include formic acid, acetic acid, propionic acid, oleic acid, linoleic acid, linolenic acid and the like.
- Formic acid and acetic acid are preferred, and acetic acid is more preferred.
- the fats and oils are not particularly limited, and may be synthetic fats and oils or processed fats and oils that may be natural fats and oils with the power of animals and plants.
- vegetable oils include olive oil, palm oil, palm oil, palm kernel oil, Amani oil, camellia oil, brown rice germ oil, rapeseed oil, rice oil, peanut oil, corn oil, wheat germ oil, large Examples include bean oil, sesame oil, cottonseed oil, castor seed oil, kapok oil, evening primrose oil, shea fat, monkey fat, cacao fat, sesame oil, safflower oil, etc.
- animal fats include pork fat, Examples thereof include milk fat, fish oil, beef tallow and the like, and oil and fat (for example, hardened oil) obtained by processing these by fractionation, hydrogenation, transesterification and the like. Needless to say, medium chain triglycerides (MCT), partial glycerides of fatty acids, phospholipids and the like can also be used.
- MCT medium chain triglycerides
- Examples of medium-chain fatty acid triglycerides include triglycerides having 6 to 12, preferably 8 to 12 carbon atoms, respectively.
- Examples of partial glycerides of fatty acids include, for example, carbon number of fatty acids.
- olive oil, rice oil, soybean oil, rapeseed oil, MCT, etc. are particularly preferred, such as olive oil, palm oil, palm oil, norm kernel oil, rapeseed oil, rice oil, soybean oil, cottonseed oil, MCT and the like. From the viewpoint of solubility of coenzyme Q, M
- CT can be used particularly preferably.
- composition of the present invention is used for food or medicine, it is preferable to use ethanol, water, fats and oils that can be used for food or medicine among the above solvents.
- composition of the present invention may contain other materials as appropriate.
- the excipient is not particularly limited, and examples thereof include sucrose, lactose, glucose, corn 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, sodium hydrogen carbonate, dextrin, crystalline cellulose, carboxymethyl cellulose, tragacanth and the like.
- the lubricant is not particularly limited, and examples thereof include talc, magnesium stearate, polyethylene glycol, silica, and hard vegetable oil.
- the binder is not particularly limited, and examples thereof include ethyl cellulose, methyl cellulose, hydroxypropyl methyl cellulose, tragacanth, shellac, gelatin, arabic gum, polybulurpyrrolidone, polybulal alcohol, polyacrylic acid, polyacrylic acid, and the like.
- Methacrylic acid ethacrylic acid
- the acid / acid inhibitor is not particularly limited !, but, for example, ascorbic acid, tocopherol, vitamin ⁇ , ⁇ -carotene, sodium bisulfite, sodium thiosulfate, sodium pyrosulfite, citrate Etc.
- the colorant is not particularly limited, and examples thereof include those permitted to be added to pharmaceuticals and foods.
- the anti-aggregation agent is not particularly limited, and examples thereof include stearic acid, talc, light anhydrous key acid, hydrous diacid and key acid.
- the above-mentioned absorption promoter is not particularly limited! However, for example, surfactants such as higher alcohols, higher fatty acids, sucrose fatty acid esters, sorbitan fatty acid esters, polyoxyethylene sorbitan fatty acid esters, etc. Can be mentioned.
- the solubilizing agent for the active ingredient is not particularly limited, and examples thereof include organic acids such as fumaric acid, succinic acid and malic acid.
- the stabilizer is not particularly limited, and examples thereof include benzoic acid, sodium benzoate, and ethyl oxybenzoate.
- Examples of active ingredients other than coenzyme Q include amino acids, vitamins, minerals, and
- Examples include phenol, organic acid, saccharide, peptide, protein and the like.
- the amount of reduced coenzyme Q contained in the composition of the present invention is not particularly limited.
- the weight of the reduced coenzyme Q contained in the product is usually about 0.01% by weight or more, preferably
- the upper limit is not particularly limited, but is usually about 70% by weight or less, preferably about 60% by weight or less, more preferably about 50% by weight or less in consideration of the viscosity of the composition.
- the temperature is not particularly limited, but the stability of reduced coenzyme Q
- the composition of the present invention is liquid at room temperature or higher (including not only solutions but also suspensions, slurries or ribosomes). Is more preferable.
- composition of the present invention can be used as it is, and can be preferably used by processing it into oral administration forms such as capsules (microcapsules, hard capsules, soft capsules), tablets, syrups and beverages. It can also be used by processing into parenteral dosage forms for creams, suppositories, toothpastes and the like. Particularly preferred are capsules, especially soft capsules.
- the capsule base material is not particularly limited, and cow bone, cow skin, pig skin, fish skin And other base materials (for example, thickening stabilizers (carrageenan, alginic acid that can be used as a food additive, seaweed-derived products such as alginic acid, and plant seed-derived products such as locust bean gum and guar gum) Etc.) and manufacturing agents (such as celluloses) can also be used.
- thickening stabilizers carrageenan, alginic acid that can be used as a food additive, seaweed-derived products such as alginic acid, and plant seed-derived products such as locust bean gum and guar gum) Etc.
- manufacturing agents such as celluloses
- the stabilization method and the production method of the present invention are preferably allowed to coexist in a deoxygenated atmosphere. That is, in order to maximize the effects of the present invention, it is preferable to carry out the method of the present invention in a deoxygenated atmosphere such as an inert gas atmosphere such as nitrogen. It is preferred to prepare and Z or store the product.
- a deoxygenated atmosphere such as an inert gas atmosphere such as nitrogen. It is preferred to prepare and Z or store the product.
- the above processing and storage after heating are preferably performed in a deoxygenated atmosphere such as the above inert gas atmosphere.
- reduced coenzyme Q can be suitably protected from oxidation
- the composition can be provided in the absence of a reducing agent such as dehydroascorbic acid.
- a highly bioresorbable composition of reduced coenzyme Q is provided.
- the ratio of 10 does not specify the upper limit.
- the mixture was stirred at 78 ° C. to carry out a reduction reaction. After 30 hours, the mixture was cooled to 50 ° C, and while maintaining the same temperature, 40 g of ethanol, 140 g of hexane, and 140 g of water were added in this order. After removing the aqueous layer, the organic layer is concentrated under reduced pressure to reduce the reduced coenzyme Q.
- Reduced coenzyme Q (mixed with 0.15 g of elemental Q and containing 1.5% by weight of reduced coenzyme Q (
- the mixture was cooled to 2 ° C at a cooling rate of 1 to obtain a white slurry.
- the resulting slurry was filtered under reduced pressure, and the wet crystals were washed in the order of cold ethanol, cold water, and cold ethanol (the temperature of the cold solvent used for washing was 2 ° C), and the wet crystals were further dried under reduced pressure (20- (40 ° C, l-30 mmHg), thereby obtaining 9.5 g of white dry crystals. All operations except drying under reduced pressure were performed under a nitrogen atmosphere.
- the obtained crystals contained 0.1% by weight of reduced coenzyme Q11, and the weight ratio of reduced coenzyme Q oxidized coenzyme Q was 99.4 / 0.6.
- Reduced coenzyme Q 10 does not contain reduced coenzyme Q 10 (reduced coenzyme Q 10 Z oxidized coenzyme Q
- CD (SD) rats (5 weeks old, 15 males, 15 females, body weight 260g-300g) were divided into 3 groups of 5 males and 5 females.
- corn oil was orally administered once a day for 14 days at a dose of 3 ml Zkg as a control group.
- the dose of reduced coenzyme Q is 600 mgZkg.
- a corn oil solution of reduced coenzyme Q prepared in the above was administered at a dose of 3 mlZkg for 14 days a day.
- the third group contains the reduced coenzyme Q prepared in Production Example 1 so that the dose of reduced coenzyme Q is 600 mgZkg.
- FIG. 1 The results are shown in FIG. In FIG. 1, the vertical axis represents the total coenzyme Q concentration in plasma, and each bar represents the mean standard deviation. As is clear from Fig. 1, in both male and female groups, the total plasma coenzyme Q concentration in the reduced coenzyme Q group was lower than that in the reduced coenzyme Q group.
- a gelatin soft capsule containing 30 mg of reduced coenzyme Q was obtained.
- Rapeseed oil 33 0% by weight Hardened oil 17.0% by weight
- the remaining 5 animals have a mixture of reduced coenzyme Q and reduced coenzyme Q (reduced coenzyme Q
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Organic Chemistry (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Diabetes (AREA)
- Emergency Medicine (AREA)
- Nutrition Science (AREA)
- Biochemistry (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Hospice & Palliative Care (AREA)
- Toxicology (AREA)
- Birds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Fodder In General (AREA)
- Cosmetics (AREA)
Abstract
Description
Claims
Priority Applications (9)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN2007800153912A CN101432256B (zh) | 2006-04-28 | 2007-04-27 | 稳定还原型辅酶q10的方法 |
DK07742687.2T DK2017251T3 (en) | 2006-04-28 | 2007-04-27 | Method for Stabilizing Reduced Coenzyme Q10 |
AU2007244232A AU2007244232B2 (en) | 2006-04-28 | 2007-04-27 | Method for stabilization of reduced coenzyme Q10 |
CA2650686A CA2650686C (en) | 2006-04-28 | 2007-04-27 | Method for stabilization of reduced coenzyme q10 |
ES07742687.2T ES2639567T3 (es) | 2006-04-28 | 2007-04-27 | Método para la estabilización de la coenzima reducida Q10 |
EP07742687.2A EP2017251B1 (en) | 2006-04-28 | 2007-04-27 | Method for stabilization of reduced coenzyme q10 |
PL07742687T PL2017251T3 (pl) | 2006-04-28 | 2007-04-27 | Sposób stabilizacji zredukowanego koenzymu Q10 |
JP2008513310A JP5286081B2 (ja) | 2006-04-28 | 2007-04-27 | 還元型補酵素q10の安定化方法 |
KR1020087029021A KR101376344B1 (ko) | 2006-04-28 | 2008-11-27 | 환원형 보효소 q10의 안정화 방법 |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2006-126897 | 2006-04-28 | ||
JP2006126897 | 2006-04-28 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2007126083A1 true WO2007126083A1 (ja) | 2007-11-08 |
Family
ID=38655603
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/JP2007/059252 WO2007126083A1 (ja) | 2006-04-28 | 2007-04-27 | 還元型補酵素q10の安定化方法 |
Country Status (12)
Country | Link |
---|---|
US (1) | US7829080B2 (ja) |
EP (2) | EP3279180A1 (ja) |
JP (1) | JP5286081B2 (ja) |
KR (1) | KR101376344B1 (ja) |
CN (1) | CN101432256B (ja) |
AU (1) | AU2007244232B2 (ja) |
CA (1) | CA2650686C (ja) |
DK (1) | DK2017251T3 (ja) |
ES (1) | ES2639567T3 (ja) |
PL (1) | PL2017251T3 (ja) |
TW (1) | TW200808344A (ja) |
WO (1) | WO2007126083A1 (ja) |
Families Citing this family (16)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102258503B (zh) | 2004-01-22 | 2019-08-16 | 迈阿密大学 | 局部辅酶q10制剂及其使用方法 |
US20070053985A1 (en) * | 2005-08-24 | 2007-03-08 | Kaneka Corporation | Coenzyme Q10-containing fine particle with excellent dispersibility |
EP3607937A1 (en) | 2007-03-22 | 2020-02-12 | Berg LLC | Topical formulations having enhanced bioavailability |
JP6058263B2 (ja) | 2008-04-11 | 2017-01-11 | バーグ リミテッド ライアビリティ カンパニー | 癌細胞においてアポトーシスを誘導する方法および使用 |
US20110020312A1 (en) | 2009-05-11 | 2011-01-27 | Niven Rajin Narain | Methods for treatment of metabolic disorders using epimetabolic shifters, multidimensional intracellular molecules, or environmental influencers |
EP2489652B1 (en) * | 2009-10-16 | 2018-07-25 | Kaneka Corporation | Method for producing reduced coenzyme q10, method for stabilizing same, and composition comprising same |
SG10202010355PA (en) | 2010-03-12 | 2020-11-27 | Berg Llc | Intravenous formulations of coenzyme q10 (coq10) and methods of use thereof |
WO2011132718A1 (ja) * | 2010-04-20 | 2011-10-27 | 株式会社カネカ | 還元型補酵素q10含有組成物とその製造方法及び安定化方法 |
CN101966171B (zh) * | 2010-09-30 | 2012-10-24 | 杭州华东医药集团康润制药有限公司 | 水溶性还原型辅酶q10组合物及其制备方法 |
CN103608323B (zh) | 2011-04-04 | 2016-08-17 | 博格有限责任公司 | 治疗中枢神经系统肿瘤的方法 |
MX351781B (es) | 2011-06-17 | 2017-10-30 | Berg Llc | Composiciones farmaceuticas inhalables. |
RU2509760C2 (ru) * | 2011-07-11 | 2014-03-20 | Закрытое акционерное общество "Научно-производственное объединение "ДОМ ФАРМАЦИИ" | ВОДОРАСТВОРИМЫЙ МОЛЕКУЛЯРНЫЙ КОМПЛЕКС ВКЛЮЧЕНИЯ ВОССТАНОВЛЕННОЙ ФОРМЫ КОЭНЗИМА Q10 В β-ЦИКЛОДЕКСТРИНЕ И СПОСОБ ЕГО ПРЕПАРАТИВНОГО ПОЛУЧЕНИЯ |
AU2014251045B2 (en) | 2013-04-08 | 2019-06-13 | Berg Llc | Treatment of cancer using coenzyme Q10 combination therapies |
CN103211217A (zh) * | 2013-04-25 | 2013-07-24 | 福建永生活力生物工程有限公司 | 一种增强免疫力功能的保健软胶囊及其制备方法 |
SG11201601583TA (en) | 2013-09-04 | 2016-04-28 | Berg Llc | Methods of treatment of cancer by continuous infusion of coenzyme q10 |
US11471426B2 (en) | 2019-10-16 | 2022-10-18 | American River Nutrition, Llc | Compositions comprising quinone and/or quinol and methods of preparations and use thereof |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH10109933A (ja) | 1996-08-16 | 1998-04-28 | Kanegafuchi Chem Ind Co Ltd | 医薬組成物 |
WO2001052822A1 (en) | 2000-01-20 | 2001-07-26 | Chopra Raj K | Reduced form of coenzyme q in high bioavailability stable dosage forms and related applications |
WO2003006409A1 (en) | 2001-07-13 | 2003-01-23 | Kaneka Corporation | Method of producing reduced coenzyme q10 crystals with excellent handling properties |
WO2003006408A1 (en) | 2001-07-13 | 2003-01-23 | Kaneka Corporation | Method of producing reduced coenzyme q10 using solvent with high oxidation-protective effect |
WO2003032967A1 (en) | 2001-10-10 | 2003-04-24 | Kaneka Corporation | Method of stabilizing reduced coenzyme q10 |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS5577895A (en) * | 1978-12-07 | 1980-06-12 | Nisshin Flour Milling Co Ltd | Preparation of coenzyme q11 |
US6878514B1 (en) * | 1999-03-30 | 2005-04-12 | Purdue Research Foundation | Methods for identifying agents that inhibit serum aging factors and uses and compositions thereof |
JP2006126897A (ja) | 2004-10-26 | 2006-05-18 | Matsushita Electric Works Ltd | 煙感知器用試験器 |
-
2007
- 2007-04-27 PL PL07742687T patent/PL2017251T3/pl unknown
- 2007-04-27 ES ES07742687.2T patent/ES2639567T3/es active Active
- 2007-04-27 EP EP17181460.1A patent/EP3279180A1/en not_active Withdrawn
- 2007-04-27 CN CN2007800153912A patent/CN101432256B/zh active Active
- 2007-04-27 WO PCT/JP2007/059252 patent/WO2007126083A1/ja active Application Filing
- 2007-04-27 TW TW096115173A patent/TW200808344A/zh unknown
- 2007-04-27 AU AU2007244232A patent/AU2007244232B2/en active Active
- 2007-04-27 CA CA2650686A patent/CA2650686C/en active Active
- 2007-04-27 US US11/741,290 patent/US7829080B2/en active Active
- 2007-04-27 JP JP2008513310A patent/JP5286081B2/ja active Active
- 2007-04-27 EP EP07742687.2A patent/EP2017251B1/en active Active
- 2007-04-27 DK DK07742687.2T patent/DK2017251T3/en active
-
2008
- 2008-11-27 KR KR1020087029021A patent/KR101376344B1/ko active IP Right Grant
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH10109933A (ja) | 1996-08-16 | 1998-04-28 | Kanegafuchi Chem Ind Co Ltd | 医薬組成物 |
WO2001052822A1 (en) | 2000-01-20 | 2001-07-26 | Chopra Raj K | Reduced form of coenzyme q in high bioavailability stable dosage forms and related applications |
WO2003006409A1 (en) | 2001-07-13 | 2003-01-23 | Kaneka Corporation | Method of producing reduced coenzyme q10 crystals with excellent handling properties |
WO2003006408A1 (en) | 2001-07-13 | 2003-01-23 | Kaneka Corporation | Method of producing reduced coenzyme q10 using solvent with high oxidation-protective effect |
WO2003032967A1 (en) | 2001-10-10 | 2003-04-24 | Kaneka Corporation | Method of stabilizing reduced coenzyme q10 |
Non-Patent Citations (2)
Title |
---|
MATSURA T. ET AL.: "Antioxidant role of cellular reduced coenzyme Q homologs and alpha-tocopherol in free radical-induced injury of hepatocytes isolated from rats fed diets with different vitamin E contents", BIOCHIMICA ET BIOPHYSICA ACTA, vol. 1127, 1992, pages 277 - 283, XP003018946 * |
NUTRITION RESEARCH, vol. 13, 1993, pages 667 - 676 |
Also Published As
Publication number | Publication date |
---|---|
CA2650686A1 (en) | 2007-11-08 |
US7829080B2 (en) | 2010-11-09 |
AU2007244232B2 (en) | 2012-07-19 |
EP2017251A1 (en) | 2009-01-21 |
JP5286081B2 (ja) | 2013-09-11 |
US20070258966A1 (en) | 2007-11-08 |
KR101376344B1 (ko) | 2014-03-20 |
CN101432256B (zh) | 2012-11-28 |
EP3279180A1 (en) | 2018-02-07 |
TW200808344A (en) | 2008-02-16 |
AU2007244232A1 (en) | 2007-11-08 |
KR20090017547A (ko) | 2009-02-18 |
CN101432256A (zh) | 2009-05-13 |
JPWO2007126083A1 (ja) | 2009-09-10 |
EP2017251A4 (en) | 2013-01-09 |
PL2017251T3 (pl) | 2017-12-29 |
DK2017251T3 (en) | 2017-09-18 |
CA2650686C (en) | 2014-12-16 |
ES2639567T3 (es) | 2017-10-27 |
EP2017251B1 (en) | 2017-07-19 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
WO2007126083A1 (ja) | 還元型補酵素q10の安定化方法 | |
JP3790530B2 (ja) | 還元型補酵素q10の安定化法 | |
JPWO2007126086A1 (ja) | 還元型補酵素q10の精製方法 | |
JP4598873B2 (ja) | 含水有機溶媒を用いる還元型補酵素q10の製造方法 | |
JP3867927B2 (ja) | 還元型補酵素q10の安定化法 | |
JP3892881B2 (ja) | 還元型補酵素q10の安定化法 | |
Ueda et al. | Method of stabilizing reduced coenzyme Q10 | |
Ueda et al. | Stabilization method of reduced coenzyme Q 10 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
121 | Ep: the epo has been informed by wipo that ep was designated in this application |
Ref document number: 07742687 Country of ref document: EP Kind code of ref document: A1 |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2008513310 Country of ref document: JP |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2650686 Country of ref document: CA |
|
WWE | Wipo information: entry into national phase |
Ref document number: 200780015391.2 Country of ref document: CN |
|
NENP | Non-entry into the national phase |
Ref country code: DE |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2007244232 Country of ref document: AU |
|
WWE | Wipo information: entry into national phase |
Ref document number: 4513/KOLNP/2008 Country of ref document: IN |
|
REEP | Request for entry into the european phase |
Ref document number: 2007742687 Country of ref document: EP |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2007742687 Country of ref document: EP |
|
ENP | Entry into the national phase |
Ref document number: 2007244232 Country of ref document: AU Date of ref document: 20070427 Kind code of ref document: A |
|
WWE | Wipo information: entry into national phase |
Ref document number: 1020087029021 Country of ref document: KR |