WO2006025247A1 - ミトコンドリア賦活剤 - Google Patents
ミトコンドリア賦活剤 Download PDFInfo
- Publication number
- WO2006025247A1 WO2006025247A1 PCT/JP2005/015401 JP2005015401W WO2006025247A1 WO 2006025247 A1 WO2006025247 A1 WO 2006025247A1 JP 2005015401 W JP2005015401 W JP 2005015401W WO 2006025247 A1 WO2006025247 A1 WO 2006025247A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- coenzyme
- mitochondrial
- disease
- derivative
- composition
- Prior art date
Links
Classifications
-
- 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
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/12—Ketones
- A61K31/122—Ketones having the oxygen directly attached to a ring, e.g. quinones, vitamin K1, anthralin
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4738—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4745—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/12—Carboxylic acids; Salts or anhydrides thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/04—Drugs for disorders of the muscular or neuromuscular system for myasthenia gravis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- 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
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
- A61P39/06—Free radical scavengers or antioxidants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
Definitions
- the present invention relates to a mitochondrial activator comprising a pyroguchi quinoline quinone derivative as an active ingredient.
- the present invention also relates to a mitochondrial activator comprising reduced coenzymes Q and Z or oxidized coenzyme Q and a citrate derivative as active ingredients.
- the mitochondrial activator here is a composition capable of preventing or ameliorating various diseases related to attenuation or failure of mitochondrial function such as diabetes, mitochondrial disease and brain disease.
- Mitochondria are organelles in the cell that perform various metabolism and energy production! It ’s known! Adenosine triphosphate (ATP), which is particularly important as bioenergy, is an important product of mitochondria. Decreased mitochondrial activity immediately leads to ATP death, and various diseases occur due to ATP death. For example, neuropathy such as heart disease, myasthenia, diabetes, liver disease, mitochondrial disease (mitochondrial dysfunction), brain disease (eg Parkinson's disease, Huntington's disease, Alzheimer's disease, amyotrophic lateral sclerosis) Diabetes mellitus is particularly important.
- ATP adenosine triphosphate
- Diabetes is the most common and serious lifestyle-related disease, and more than 1 million patients are known worldwide. In addition, the number of people called diabetes reserves with slightly elevated blood sugar levels far exceeds the number of patients. Thus, diabetes is a serious disease worldwide. As diabetes, type I diabetes (insulin-dependent diabetes) due to insufficient insulin secretion and type II diabetes (insulin-independent diabetes) due to decreased sensitivity to insulin are known. Many people with diabetes have type II diabetes, and this type of diabetes often develops due to inappropriate lifestyle habits such as overeating. This type II diabetes is thought to result from a combination of impaired insulin secretion in the pancreatic islets of Langeron and a decrease in insulin sensitivity in each tissue.
- Insulin secretion from pancreatic islets is triggered by the biosynthesis of ATP in response to elevated blood glucose levels. Therefore, mitochondrial dysfunction is known to suppress insulin secretion and contribute to diabetes. In recent years, mitochondrial genes It has become clear that diabetes develops due to abnormalities.
- Coenzyme Q is an essential component that is widely distributed in living organisms up to bacterial power and mammals, and is known to be a component of the mitochondrial electron transport system in cells in the organism. Coenzyme Q plays a role as a transfer component in the electron transport system by repeating oxidation and reduction in mitochondria, and reduced coenzyme Q is known to exhibit an antioxidant effect. In humans, coenzyme Q has 10 repeating side-chains.
- Non-patent Document 1 In a chronic toxicity study, 1200 mgZKgZ was reported to have no toxic effects even after daily administration for 52 weeks (Non-patent Document 1).
- Coenzyme Q is an oxidized coenzyme Q strength in Japan as a congestive heart failure drug
- Non-patent Document 2 discloses a report suggesting an effect on the relationship between oxidized coenzyme Q10 and diabetes.
- Reduced coenzyme Q10 is an active form of acid coenzyme Q10, but it is easily oxidized by oxygen in the air and converted to oxidized coenzyme Q10. The power that has been made in the past has been strong.
- Pillow mouth quinoline quinone is a substance that has been shown to have potential as a new vitamin in 2003, and is known to exhibit strong anti-acidic activity. Its usefulness has been reported for promotion (Patent Document 2), treatment of diabetic complications (Patent Document 3), suppression of melanin production (Patent Document 4), and the like. However, strong toxicity to the kidney has been reported (Patent Document 5), and there is a problem that the so-called safety range is narrow.
- Non-patent Document 2 it has been reported that mitochondrial dysfunction occurs when mice are raised on a diet lacking pyroguchi quinoline quinone.
- Non-patent Document 2 Well known for the activation of mitochondrial function! / Coenzyme Q and pyroguchi quinoline quinone both have anti-acidic activity and have a quinone skeleton. Forces with similarities in point There is no knowledge about these synergies.
- Patent Document 1 WO03Z077895
- Patent Document 2 Japanese Patent Laid-Open No. 06-211660
- Patent Document 3 Japanese Patent Laid-Open No. 06-256191
- Patent Document 4 Japanese Patent Laid-Open No. 08-020512
- Patent Document 5 Japanese Patent Laid-Open No. 05-78247
- Non-Patent Document 1 K. D. Williams, et al. J. Agric. Food Chem. 47 3756-376 3, 1999
- Non-Patent Document 2 R. Rucker, et al. In Biochemical and Molecular Biology of Vitamin B— 6 and PQQ-dependent Proteins 61—66, 2000 Disclosure of the Invention
- An object of the present invention is to provide a composition that is highly effective in mitochondrial activation activity and that can be expected to treat or prevent various diseases (particularly diabetes).
- the present invention provides the following:
- a mitochondrial activator comprising pyroguchi quinoline quinone or a derivative thereof.
- n represents an integer of 1 to 12.
- n represents an integer of 1 to 12
- Q is an oxidized coenzyme Q
- Antioxidants include vitamin C, vitamin C derivatives, probucol, lycopene, vitamin A, strength rotenoids, vitamin B, vitamin B derivatives, flavonoids, polyphenols, glutathione, selenium, sodium thiosulfate, vitamins E, Vitamin E derivatives, Pycnogenol, Flavangenol, Cuenate, Cuenate derivatives, Superoxide dismutase (SOD), Glutathione peroxidase, Glutathione S-transferase, Glutathione reductase, Catalase and Ascorbate peroxidase
- SOD superoxide dismutase
- Glutathione peroxidase Glutathione S-transferase
- Glutathione reductase Catalase and Ascorbate peroxidase
- the composition according to [5] which is at least one compound selected from the group consisting of:
- a pharmaceutical or food composition comprising the mitochondrial activator according to any one of [1] to [4] and a pharmaceutical or food acceptable carrier.
- composition for preventing or treating a disease caused by mitochondrial dysfunction comprising an effective amount of any one of the mitochondrial activators according to [1] to [4].
- a method comprising administering to a mammalian subject an effective amount of any of the mitochondrial activators according to any one of [I] to [4].
- a method comprising mixing.
- a method comprising mixing.
- a pharmaceutical or food composition comprising the mitochondrial activator according to any one of [14] to [16] and a pharmaceutical or food acceptable carrier.
- Antioxidants include vitamin C, vitamin C derivatives, probucol, lycopene, vitamin A, carotenoids, vitamin B, vitamin B derivatives, flavonoids, polyphenols, glutathione, selenium, sodium thiosulfate, vitamin E , Vitamin E derivatives, Pycnogenol, Flavangenol, Pyromouth quinoline quinone, Pyromouth quinoline quinone derivatives, Superoxide dismutase (SOD), Glutathione peroxidase, Glutathione S transferase, Dartathione reductase, Catalase, and Ascorbic acid [18] The composition of [18], which is one or more compounds selected from the group consisting of peroxidase.
- a composition comprising an effective amount of a mitochondrial activator according to any one of [14] to [16], which is a preventive or therapeutic agent for diseases caused by mitochondrial dysfunction in mammals.
- [22] A method for preventing or treating a disease caused by mitochondrial dysfunction in a mammalian subject, wherein [14] to [16] an effective amount of any mitochondrial activator is given to the mammalian subject, A method comprising administering.
- the disease is selected from the group consisting of diabetes, mitochondrial disease and brain disease The prevention or treatment method according to [22].
- a method comprising mixing.
- a method comprising mixing.
- a mitochondrial activator comprising citrate or a derivative thereof.
- Mitigation of mitochondrial activity which is an important organelle producing bioenergy, causes various diseases, so activation of mitochondrial activity is highly useful for health.
- the pyroguchi quinoline quinone derivative itself has a mitochondrial activating activity, and that a synergistic mitochondrial activating activity can be obtained by combining reduced coenzyme Q and a pyroguchi quinoline quinone derivative. It was. It was also found that a combined mitochondria activation activity can be obtained by combining reduced coenzyme Q and Z or acid-coenzyme coenzyme Q and a citrate derivative. Since pyroguchi quinoline quinone derivatives have safety issues, quenoic acid has a problem of taking a sufficient amount due to the strength of its acidity. What was done Thus, a safer and more useful composition can be provided.
- Mitochondrial activation in the present invention may mean mitochondrial activity. Specifically, when a compound is administered to a test subject, the compound has mitochondrial activation activity if the mitochondrial activity of the subject is increased compared to that of the control subject. Mitochondrial activity can be assessed, for example, by measuring ATP production capacity.
- the first of the present invention is a mitochondrial activator comprising pyroguchi quinoline quinone or a derivative thereof as an active ingredient.
- Pyromouth quinoline quinone is 2,7,9-tricarboxy 1 1H-pyro mouth [2,3-f] quinoline 1 4, 5-dione.
- a derivative of a compound is a compound that includes the compound itself and is capable of undergoing minor structural changes in the compound.
- a compound in which a hydrogen atom or a specific atomic group in the compound is substituted by another atom or atomic group is understood to be a derivative of the compound.
- Examples of the pyroguchi quinoline quinone derivatives include pyroguchi quinoline quinol, imidazole pyrroloquinoline quinone, imidazole pyrroloquinoline quinone derivatives, pyroguchi quinoline quinone latinate and the like. Needless to say, the pyro-quinoline quinone itself may be used. Of these, pyroguchi quinoline quinone, pyroguchi quinoline quinone lactone, pyroguchi quinoline quinolate and the like are more preferable.
- pyroguchi quinoline quinone derivatives commercially available products may be used as they are, or yeasts, dried fungi, and foods containing a high level of pyro quinoline quinone derivatives may be used.
- pyrroloquinoline quinone or a derivative thereof may be referred to as pyrroloquinoline quinones.
- the mitochondrial activator in the present invention includes, as an active ingredient, the following formula (1) in addition to the above-mentioned pyroguchi quinoline quinone or its derivative:
- An oxidized coenzyme Q represented by (wherein n represents an integer of 1 to 12) may be contained! / ⁇ .
- the method for obtaining coenzyme Q is not particularly limited, and can be obtained by a conventionally known method such as fermentation, chemical synthesis, extraction from a natural product, or the like. Most of the coenzyme Q obtained in this way is an acid type, and as the acid type coenzyme Q, the coenzyme Q obtained in this way can be used as it is or further purified. May be performed.
- Reduced coenzyme The method for obtaining Q is not particularly limited. For example, after obtaining coenzyme Q by the above known method, a method of concentrating reduced coenzyme Q in the effluent by chromatography can be employed. .
- a general reducing agent such as sodium borohydride or sodium dithionite (no, idulosulfite sodium) is added to the above coenzyme Q as necessary, and the above coenzyme is prepared by a conventional method. Concentration by chromatography may be carried out after reducing oxidized coenzyme Q contained in Q to reduce coenzyme Q. It can also be obtained by a method in which the above reducing agent is allowed to act on existing high-purity coenzyme Q (oxidized coenzyme Q). Alternatively, cells containing reduced coenzyme Q can also be used.
- a general reducing agent such as sodium borohydride or sodium dithionite (no, idulosulfite sodium) is added to the above coenzyme Q as necessary, and the above coenzyme is prepared by a conventional method. Concentration by chromatography may be carried out after reducing oxidized coenzyme Q contained in Q to reduce coenzyme Q. It can also be obtained by a method in which
- the ratio of the reduced form in coenzyme Q is usually calculated by quantifying oxidized coenzyme Q and reduced coenzyme Q in the sample with an HPLC system using a UV detector, and calculating the ratio.
- a system that incorporates an electrochemical detector is useful for measuring the proportion of reduced forms in living organisms or samples, because it can specifically measure acid-reduced substances and has high sensitivity. High nature.
- an electrochemical detector manufactured by Shiseido Co., Ltd. was incorporated into an HPLC analyzer manufactured by Shimadzu Corporation, and measurement was performed under the following HPLC conditions. That is, column: YMC-Pack (ODS-A 303), detection wavelength: 275 nm, mobile phase: methanol (88%), hexane (12%), flow rate: lm / min.
- the oxidized coenzyme Q when simply described as “coenzyme Q”, the oxidized coenzyme Q, reduced coenzyme Q, a mixture of oxidized coenzyme Q and reduced coenzyme Q! / It also means a gap.
- the contents of coenzyme Q and the pyroguchi quinoline quinone derivative are not particularly limited and can be appropriately determined depending on the product concept and the like. Increasing the proportion of reduced coenzyme Q in coenzyme Q may increase costs due to its stability measures, but it has a higher and synergistic effect with pyroguchi quinoline quinone derivatives. obtain.
- the present invention also relates to a synergistic composition.
- the synergistic composition of the present invention can achieve an effect equivalent to or higher than the effect of applying each active ingredient alone at a dose lower than the effective amount of each active ingredient, that is, a synergistic effective amount.
- the pyroguchi quinoline quinone derivative enhances the mitochondrial activation activity of the coenzyme Q (and vice versa) when combined with the reduced coenzyme Q and Z or the acid ⁇ type coenzyme Q ) Is understood. Therefore, the enhancer of the mitochondrial activator of coenzyme Q, including a pyroguchi quinoline quinone derivative, is also an aspect of the present invention. Conversely, an enhancer of a mitochondrial activator of a pyroguchi quinoline quinone derivative containing coenzyme Q is also an aspect of the present invention. It is also possible to use yeast, fungus dried products, and foods that highly contain a pyroguchi quinoline quinone derivative.
- the weight ratio of the reduced coenzyme Q or oxidized coenzyme Q of the present invention to the pyroguchi quinoline quinone derivative is not particularly limited. For example, for 1 part by weight of the pyroquinoquinone quinone derivative, it is 100! 10, 10! 1, 1! 0.1, and ⁇ 3 ⁇ 4 0.1. 0. OlMm Some coenzyme Q can be used. Preferably, the weight ratio is about 10: 1 to 1:10. A weight ratio of about 1: 1 is most desirable. Moreover, only the pyroguchi quinoline quinone derivative may be used as an active ingredient.
- the second mitochondrial activator in the present invention contains a citrate derivative as an active ingredient. It may be an activator containing only a succinic acid derivative as an active ingredient, and the reduced coenzyme Q and Z represented by the formula (1) or the oxidized coenzyme represented by the formula (2) It may be a composition containing Q and a citrate derivative. Since synergistic mitochondrial activation activity is obtained, citrate derivative and coenzyme Q must be included as active ingredients. Is preferred.
- the reduced coenzyme Q and oxidized coenzyme Q used in the second mitochondrial activator of the present invention the reduced coenzyme Q and acid salt used in the first mitochondrial activator described above are used. The same as described for type coenzyme Q.
- a derivative in the present specification is a compound formed by a small structural change in a certain compound. It is understood that a compound substituted by a hydrogen atom or a specific atomic group or other atom or atomic group in a compound is a derivative of the compound. In the present specification, the compound itself is also included in its derivatives.
- the citrate derivative specifically, citrate, potassium citrate, sodium citrate, calcium citrate, isopropyl citrate, iron citrate and the like are used.
- the citrate derivative is sodium citrate.
- the contents of coenzyme Q and citrate derivative are not particularly limited, and can be appropriately determined depending on the product concept and the like. Increasing the proportion of reduced coenzyme Q in coenzyme Q may increase costs due to its stability measures, but may have a higher synergistic effect with citrate derivatives.
- the citrate derivative when combined with reduced coenzyme Q and Z or oxidized coenzyme Q, the citrate derivative is understood to enhance the mitochondrial activation activity of the coenzyme Q.
- an enhancer of the mitochondrial activator of coenzyme Q containing a citrate derivative is also an aspect of the present invention.
- an enhancer of mitochondrial activator of citrate derivative containing coenzyme Q is also one aspect of the present invention. It is also possible to use yeast, dried fungi, and foods that contain a high amount of citrate derivatives.
- the weight ratio of the coenzyme Q of the present invention to the succinic acid derivative can be, for example, 1: 100 to 10: 1.
- the quantity ratio is more preferably about 1:10, which is preferably about 1: 1, but is not particularly limited.
- the present invention provides:
- n represents an integer of 1 to 12
- n an integer of 1 to 12
- Q an oxidized coenzyme
- a composition for mitochondrial utilization is also provided. About these various components already As explained.
- the first mitochondrial activator shows a pyroguchi quinoline quinone derivative, preferably a pyroguchi quinoline quinone derivative and coenzyme Q
- the second mitochondrial activator shows An acid derivative, preferably a citrate derivative and coenzyme Q are shown.
- coenzyme Q is oxidized coenzyme Q! ⁇ may contain only reduced coenzyme Q as an active ingredient, or a mixture of reduced coenzyme Q and oxidized coenzyme Q. Goods may be used as active ingredients. It is preferable that the coenzyme Q contains at least a reduced coenzyme Q because a higher synergistic effect can be obtained with the pyroguchi quinoline quinone or citrate derivative.
- the ratio of reduced coenzyme Q and oxidized coenzyme Q is not particularly limited, but the ratio of reduced coenzyme Q to the total coenzyme Q is about 60% by weight or more and about 100% by weight or less. More preferably, it is about 80% by weight or more and about 99% by weight or less.
- the reduced coenzyme Q that can be used in the present invention as shown in the above formula (1), the ability to use a side chain repeating unit (wherein n) is 1 to 12 can be used. Among them, those having 10 side chain repeat units, that is, reduced coenzyme Q can be used particularly preferably.
- n side chain repeating unit 1 to 12
- those having 10 side chain repeat units, that is, reduced coenzyme Q can be used particularly preferably.
- the mitochondrial activator of the present invention may be formulated into a desired form.
- the mitochondrial activator of the present invention contains about 0.1 to 100% by weight, preferably about 1 to 99% by weight, more preferably about 10 to 10% of the active ingredient of the present invention (which may be two or more). It may contain 90% by weight.
- the dosage form of the mitochondrial activator of the present invention is not particularly limited, and may be an oral preparation or applied directly to the skin. As an oral preparation, for example, a powder or a binder may be added and a powder or granule, which may be a granule, may be filled into a capsule to form a capsule.
- oils oily higher fatty acids, higher fatty acid monodalysides, surfactants or mixtures thereof may be added and filled in oil to form soft capsules.
- those mainly composed of gelatin or other water-soluble polymer substances can be used.
- Such capsules also include microcapsules.
- the liquid It is also possible to use a bulking agent.
- mitochondrial activator of the present invention in addition to the above active ingredients, other pharmaceutical carriers acceptable in terms of pharmacology or food engineering may be appropriately added and mixed by a conventional method.
- a material is not particularly limited, and examples thereof include excipients, disintegrants, lubricants, binders, anti-oxidation agents, coloring agents, anti-aggregation agents, absorption accelerators, solubilizers, and stabilization agents. Agents.
- the excipient is not particularly limited, and examples thereof include sucrose, lactose, glucose, corn starch (corn flour), 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, crystal cellose, carboxymethyl cellulose, tragacanth and the like.
- the lubricant is not particularly limited, and examples thereof include talc, magnesium stearate, polyethylene glycol, silica, hydrogenated vegetable oil, and the like.
- the binder is not particularly limited, and examples thereof include ethyl cellulose, methyl cellulose, hydroxypropyl methyl cellulose, tragacanth, shellac, gelatin, gum arabic, polybutylpyrrolidone, polybutyl alcohol, polyacrylic acid, polymethacrylic acid. And sorbitol.
- the anti-oxidation agent is not particularly limited, and examples thereof include ascorbic acid, tocopherol, vitamin koji, ⁇ -carotene, sodium hydrogen sulfite, sodium thiosulfate, sodium pyrosulfite, and citrate.
- the colorant is not particularly limited, and for example, those permitted to be added to pharmaceuticals can be used.
- the anti-aggregation agent is not particularly limited, and examples thereof include stearic acid, talc, light anhydrous caustic acid, hydrous nitric acid, and caustic acid.
- the absorption promoter is not particularly limited.
- interfaces such as higher alcohols, higher fatty acids, glycerin fatty acid esters, sucrose fatty acid esters, sorbitan fatty acid esters, polyoxyethylene sorbitan fatty acid esters, and polyglycerin fatty acid esters.
- An active agent etc. are mentioned.
- the dissolution aid is not particularly limited, and examples thereof include fumaric acid, succinic acid, and malic acid. Any organic acid etc. are mentioned.
- the stabilizer is not particularly limited, and examples thereof include benzoic acid, sodium benzoate, and ethyl oxybenzoate.
- the dosage form is not particularly limited.
- the above drugs are dissolved or mixed and dispersed in a suitable base to form a cream, paste, jelly, gel, or emulsion.
- liquid forms oils, liniments, lotions, creams, sprays, etc.
- base materials usually used for pharmaceuticals, cosmetics and the like can be used as long as they do not impair the effects of the present invention.
- the mitochondrial activator of the present invention can contain an antioxidant, for example, an antioxidant or an antioxidant enzyme.
- an antioxidant for example, an antioxidant or an antioxidant enzyme.
- the anti-acid substance examples include vitamin E, vitamin E derivatives, vitamin C, vitamin C derivatives, probucol, lycobene, vitamin A, carotenoids, vitamin B, vitamin B derivatives, flavonoids.
- Polyphenols, glutathione, pycnogenol, flavangenol, citrate, citrate derivatives, pyroguchi quinoline quinone, pyro quinoline quinone derivatives or selenium are suitable. The above may be used alone or in combination of two or more.
- the antioxidant enzyme is not particularly limited.
- SOD superoxide dismutase
- glutathione peroxidase glutathione peroxidase
- glutathione S transferase glutathione reductase
- glutathione reductase glutathione reductase
- catalase glutathione reductase
- ascorbate peroxidase is suitable.
- the above may be used alone, or two or more may be mixed!
- the mitochondrial activator of the present invention can contain other nourishing tonic components.
- Nourishing tonic ingredients are not particularly limited, but for example creatine, taurine, vitamin B
- Vitamin B derivatives or amino acids are suitable. The above may be used alone or in combination of two or more. By mixing these ingredients with the active ingredient of the present invention, an additive or synergistic effect can be further expected.
- the mitochondrial activator of the present invention can contain a nutritional supplement component.
- Nutritional supplements are not particularly limited, but include amino acids, metal ions, sugars, proteins, and fats. Examples include acids and vitamins.
- the form when the mitochondrial activator of the present invention is used as a general food is not particularly limited, but edible oil and fat compositions, cooking oils, spray oils, butters, margarines, short jugs, Whipped cream, concentrated milk, whiteners, dressings, pickle liquids, breads, cakes, sweets, cookies, Japanese confectionery, snacks, oil confectionery, chocolate and chocolate confectionery, rice confectionery, Frozen foods such as roux, sauces, sauces, toppings, ice confectionery, rice cakes, bakery mixes, fried foods, processed meat products, marine products, frozen entrées, frozen livestock products, and frozen agricultural products Examples include foods, cooked rice, jams, cheese, cheese foods, cheese-like foods, gums, candies, fermented milks, canned foods and beverages.
- the mitochondrial activator of the present invention can improve mitochondrial activity in the skin by being applied directly to the skin.
- the skin cell activity can improve skin tension, water retention, wrinkles, dullness, spots and the like.
- the content of various active ingredients, product form, product storage method and storage form are appropriately determined according to the product design and use of the mitochondrial activator. Is done.
- mitochondrial activator of the present invention it is possible to improve a disease involving mitochondrion, poor physical condition or skin care.
- Diseases resulting from mitochondrial dysfunction include various diseases associated with mitochondrial function impairment or failure. Such diseases include, for example, diabetes, skin disorders such as rough skin, fatigue, such as chronic fatigue syndrome, heart disease, mitochondrial disease and brain disease.
- the mitochondrial activator of the present invention can be used as a thread and composition for treating, preventing, treating or ameliorating the above diseases or conditions.
- Mammalian subjects include mammals other than humans, preferably humans.
- Effective amount means an amount of a compound that confers a prophylactic or therapeutic effect on the treated subject.
- the therapeutic effect can be objective (ie, measurable by some test or marker) or subjective (ie, subject indicates or feels the effect).
- the dose level of the compound and the frequency of administration of the combination are determined by Compound ability, metabolic stability and length of action of the compound, patient age, weight, general health, sex, diet, mode of administration and time, rate of excretion, drug combination, condition of treatment It varies depending on the severity and the treatment or prevention experienced by the patient. The determination of a suitable effective amount is within the ordinary skill in the art and can be determined empirically or experimentally.
- the daily dose should be about 10 mg per day, about 500 mg, preferably about 155 mg per day. It can be about 30 mg per day, about 300 mg, and about 50 mg per person, about 100 mg per person, and it can be administered as a single dose or multiple doses.
- the daily dose of the other active ingredient, the pyroguchi quinoline quinone derivative or the succinic acid derivative is the same as the daily dose of reduced and sputum or oxidized coenzyme Q.
- such administration may also be selected by force administered orally, such as by injection, such as transdermal, transmucosal, enteral administration, or direct injection into blood vessels.
- the present invention provides a combination wherein a synergistically effective amount of a first active ingredient and a second active ingredient are formulated and combined in separate units, such as capsules, tablets or pills.
- the present invention also provides a commercial product comprising the combination, if necessary, with instructions that it should be applied simultaneously or sequentially, or with a packaging with an indication to that effect.
- the first method for producing a mitochondrial activator of the present invention includes mixing reduced coenzyme Q and sputum or oxidized coenzyme Q in addition to the pyroguchi quinoline quinone derivative. If desired, an antioxidant and the above-mentioned pharmaceutical carrier may be mixed. Pharmaceutically or pharmaceutically applicable manufacturing methods can be combined. Similarly, a pharmaceutical or food composition can be produced.
- the second method for producing a mitochondrial activator of the present invention includes mixing reduced coenzyme Q and sputum or oxidized coenzyme Q in addition to the citrate derivative. If desired, an antioxidant and the above-mentioned pharmaceutical carrier may be mixed. Similarly, a pharmaceutical or food composition can be produced. Manufacturing methods applicable pharmaceutically or food engineering can be combined.
- Ascorbic acid was added, and the mixture was stirred at 78 ° C. to carry out a reduction reaction. After 30 hours, the mixture was cooled to 50 ° C and added with 330 g of ethanol and 70 g of water while maintaining the same temperature. While stirring this ethanol solution (containing 10 g of reduced coenzyme Q), cool to 2 ° C at a cooling rate of 10 ° CZ time.
- sodium hyposulfite (purity 75% or more) as a reducing agent was gradually added an aqueous solution of 1000 ml of water dissolved in lOOg and subjected to a reduction reaction at 25 ° C and pH 4-6. After 2 hours, the aqueous phase was also removed from the reaction solution, and the heptane phase was washed 6 times with degassed saturated saline lOOOg. As described above, all operations were performed in a nitrogen atmosphere. This heptane phase was subjected to solvent replacement under reduced pressure to prepare a 7% (wZw) ethanol solution of reduced coenzyme Q at 50 ° C.
- the crystal was precipitated by cooling to 2 ° C at a cooling rate of 10 ° CZ time. All operations were performed under a nitrogen atmosphere.
- the obtained slurry was filtered under reduced pressure, and the wet crystals were washed with cold ethanol, cold water, and cold ethanol in this order (the temperature of the cold solvent used for washing was 2 ° C), and the wet crystals were further dried under reduced pressure (20 to 40). (C, l-30 mmHg), 97 g of white dry crystals were obtained.
- Example 1 Effect of the first mitochondrial activator of the present invention on insulin secretory activity
- ATP which is an indicator of mitochondrial activity
- spleen Langernos island tissue secreting insulin in response to ATP was used to evaluate the mitochondrial activation activity of the test substance using insulin secretion as an index.
- splenic islets of Langerhans a culture kit prepared from rats (Hokudo) was used. Test the Langernos Island tissue after pre-culture in a CO incubator for 24 hours.
- the medium was mixed and replaced, and after 1 hour of culture, the effect of the test substance on ATP production was evaluated by quantifying the insulin secreted in the medium by ELISA. The results are shown in Table 1.
- Oxidized coenzyme Q, reduced coenzyme Q and pyroguchi quinoline quinone are 0.1 g / ml.
- the amount of insulin added increases the insulin concentration in the medium by 7.7 times, 8.3 times, and 5.1 times, respectively, and activates ATP production in the splenic islets of Langernos. It was.
- the combination of pyroguchi quinoline quinone and oxidized or reduced coenzyme Q makes insulin
- Example 2 Effect of second mitochondrial activator of the present invention on insulin secretory activity
- a splenic Langernos island tissue was used, and a specific substance with an insulin secretory activity as an index was used. Mitochondrial activation activity was evaluated.
- Splenic islets of Langernos A culture kit prepared by Hokudo Co., Ltd. (made by Hokudo) was used.
- test substance oxidized coenzyme Q, reduced coenzyme
- Oxidized coenzyme Q, reduced coenzyme Q and citrate are added in an amount of 0.1 gZml.
- Co-enzyme Q (reduced co-fermentation) was obtained by heating olive oil to 60 ° C and melting at 60 ° C.
- Soft capsule formulation containing 20 mg of coenzyme Q and 20 mg of pyro-quinoline quinone in one capsule
- the tablets were compressed into tablets containing 10 g and 20 mg of pyroguchi quinoline quinone.
- Co-enzyme Q (reduced co-fermentation) was obtained by heating olive oil to 60 ° C and melting at 60 ° C.
- a soft capsule formulation containing 10 mg 20 mg and 20 mg citrate was obtained.
- citrate This was adsorbed to crystalline cellulose (fine powder) and then dried.
- Corn starch, lactose, carboxymethylcellulose, and magnesium stearate were mixed with this, and an aqueous solution of polybulurpyrrolidone was added as a binder to give granules by a conventional method.
- talc as a lubricant and mixing it, 20 mg of coenzyme Q in one tablet,
- Tablets were formed into tablets containing 20 mg of acid.
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Epidemiology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Diabetes (AREA)
- Psychology (AREA)
- Hospice & Palliative Care (AREA)
- Biochemistry (AREA)
- Cardiology (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Toxicology (AREA)
- Psychiatry (AREA)
- Heart & Thoracic Surgery (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Gastroenterology & Hepatology (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
Description
Claims
Priority Applications (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AU2005278611A AU2005278611A1 (en) | 2004-08-30 | 2005-08-25 | Mitochondria activators |
JP2006531967A JPWO2006025247A1 (ja) | 2004-08-30 | 2005-08-25 | ミトコンドリア賦活剤 |
CA002578347A CA2578347A1 (en) | 2004-08-30 | 2005-08-25 | Mitochondria activators |
US11/661,419 US20070259908A1 (en) | 2004-08-30 | 2005-08-25 | Mitochondria Activators |
EP05780925A EP1785138A1 (en) | 2004-08-30 | 2005-08-25 | Mitochondria activators |
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2004249495 | 2004-08-30 | ||
JP2004249494 | 2004-08-30 | ||
JP2004-249494 | 2004-08-30 | ||
JP2004-249495 | 2004-08-30 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2006025247A1 true WO2006025247A1 (ja) | 2006-03-09 |
Family
ID=35999904
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/JP2005/015401 WO2006025247A1 (ja) | 2004-08-30 | 2005-08-25 | ミトコンドリア賦活剤 |
Country Status (8)
Country | Link |
---|---|
US (1) | US20070259908A1 (ja) |
EP (1) | EP1785138A1 (ja) |
JP (1) | JPWO2006025247A1 (ja) |
KR (1) | KR20070057218A (ja) |
AU (1) | AU2005278611A1 (ja) |
CA (1) | CA2578347A1 (ja) |
RU (1) | RU2007111720A (ja) |
WO (1) | WO2006025247A1 (ja) |
Cited By (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2006117626A (ja) * | 2004-09-24 | 2006-05-11 | Nisshin Pharma Inc | コエンザイムq10配合組成物の製造方法 |
EP2011498A1 (en) * | 2006-04-10 | 2009-01-07 | Mitsubishi Gas Chemical Company, Inc. | Brain function-improving agent, and functional food containing the improving agent |
EP2067781A1 (en) * | 2006-09-19 | 2009-06-10 | Kyowa Hakko Bio Co., Ltd. | Agent for improving insulin resistance |
JP2011075851A (ja) * | 2009-09-30 | 2011-04-14 | Sharp Corp | 電子写真感光体およびそれを備えた画像形成装置 |
JP2012001507A (ja) * | 2010-06-18 | 2012-01-05 | Osaka Prefecture Univ | Ptp1b阻害剤及び該阻害剤を含む糖尿病治療薬、皮膚外用剤並びに食品 |
WO2012020767A1 (ja) * | 2010-08-09 | 2012-02-16 | 三菱瓦斯化学株式会社 | ピロロキノリンキノンのゲル |
JP2012036094A (ja) * | 2010-08-03 | 2012-02-23 | Mitsubishi Gas Chemical Co Inc | ピロロキノリンキノン含有ソフトカプセル |
JP2015131823A (ja) * | 2015-02-23 | 2015-07-23 | 株式会社ディーエイチシー | Ii型糖尿病治療薬、及び育毛剤 |
JP2018172346A (ja) * | 2017-03-31 | 2018-11-08 | 株式会社東洋新薬 | 妊娠サポート用組成物 |
WO2020158415A1 (ja) * | 2019-01-28 | 2020-08-06 | サントリーホールディングス株式会社 | オレキシン受容体拮抗阻害用組成物 |
WO2021132077A1 (ja) * | 2019-12-27 | 2021-07-01 | サントリーホールディングス株式会社 | セサミン類及びpqqを含有する組成物 |
JP2021529781A (ja) * | 2018-06-26 | 2021-11-04 | リボノバ インコーポレイテッドRibonova Inc. | ミトコンドリア機能障害の治療方法 |
Families Citing this family (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2008048135A1 (fr) * | 2006-10-20 | 2008-04-24 | Limited Liability Company 'mitotechnology' | Composition destinée à la régénération, la stimulation de la croissance et l'adaptation de plantes à tous types de facteurs de stress |
WO2008048134A1 (fr) * | 2006-10-20 | 2008-04-24 | Limited Liability Company 'mitotechnology' | Compositions pharmaceutiques pour la prévention et le traitement de pathologies oculaires |
WO2008094061A1 (fr) * | 2007-01-29 | 2008-08-07 | Limited Liability Company 'mitotechnology' | Compositions pharmaceutiques et cosmétiques servant à accélérer le processus de cicatrisation de plaies et autres lésions superficielles |
EA201000142A1 (ru) * | 2007-04-11 | 2010-04-30 | Общество С Ограниченной Ответственностью "Митотехнология" | Композиция, замедляющая старение и увеличивающая продолжительность жизни организма, и ее применение |
JP5343845B2 (ja) * | 2007-05-21 | 2013-11-13 | 東レ株式会社 | 特定の有機酸を含有する経口製剤並びに経口製剤の溶出性及び化学的安定性の改善方法 |
US8518915B2 (en) * | 2007-06-29 | 2013-08-27 | Mitotech Sa | Use of mitochondrially-addressed compounds for preventing and treating cardiovascular diseases |
WO2010056145A1 (ru) | 2008-11-12 | 2010-05-20 | Общество С Ограниченной Ответственностью "Митотехнология" | Способ умеренного повышения протонной проводимости биологических мембран при помощи митохондриально- адресованных делокализованных катионов |
UA104320C2 (ru) | 2009-06-10 | 2014-01-27 | Общество С Ограниченной Ответственностью "Мимотех" | Фармацевтическая композиция на основе митохондриально-адресованного антиоксиданта для применения в медицинской и ветеринарной офтальмологии |
CA2789846C (en) | 2009-11-13 | 2020-02-25 | Obschestvo S Ogranichennoi Otvetstvennostyu "Mitotekh" | Pharmaceutical substances on the basis of mitochondria-addressed antioxidants |
AU2012261854B2 (en) | 2011-06-03 | 2017-11-16 | Mitotech Sa | Oral formulations of mitochondrially-targeted antioxidants and their preparation and use |
AU2012268427B2 (en) | 2011-06-06 | 2016-02-04 | Dermaforce Holdings, LLC | Skin treatments containing pyrroloquinoline quinone (PQQ) esters and methods of preparation and use thereof |
CN117426507B (zh) * | 2023-11-22 | 2024-05-03 | 广州能量生物科技有限公司 | 一种保护线粒体和溶血栓的保健食品及其制备方法 |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2003077895A1 (fr) * | 2002-03-20 | 2003-09-25 | Kaneka Corporation | Compositions contre le diabete |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1032403B1 (en) * | 1997-10-24 | 2012-05-02 | John P. Blass | Nutritional supplement for cerebral metabolic insufficiencies |
JP3742602B2 (ja) * | 2001-05-09 | 2006-02-08 | 株式会社カネカ | 還元型補酵素qの安定な溶液 |
-
2005
- 2005-08-25 CA CA002578347A patent/CA2578347A1/en not_active Abandoned
- 2005-08-25 AU AU2005278611A patent/AU2005278611A1/en not_active Abandoned
- 2005-08-25 US US11/661,419 patent/US20070259908A1/en not_active Abandoned
- 2005-08-25 KR KR1020077007155A patent/KR20070057218A/ko not_active Application Discontinuation
- 2005-08-25 RU RU2007111720/15A patent/RU2007111720A/ru not_active Application Discontinuation
- 2005-08-25 JP JP2006531967A patent/JPWO2006025247A1/ja active Pending
- 2005-08-25 WO PCT/JP2005/015401 patent/WO2006025247A1/ja active Application Filing
- 2005-08-25 EP EP05780925A patent/EP1785138A1/en not_active Withdrawn
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2003077895A1 (fr) * | 2002-03-20 | 2003-09-25 | Kaneka Corporation | Compositions contre le diabete |
Non-Patent Citations (4)
Title |
---|
HE K. ET AL: "Antioxidant and pro-oxidant properties of pyrroloquinoline quinone (PQQ): implications for its function in biological systems", BIOCHEMICAL PHARMACOLOGY, vol. 65, no. 1, 2003, pages 67 - 74, XP003006803 * |
MCINERNEY M.F. ET AL: "Effects of a 33 residue interleukin-1 beta peptide and the antioxidant PQQ on interleukin-1 beta-mediated inhibition of glucose-stimulated insulin release from cultured mouse pancreatic islets", RESEARCH COMMUNICATIONS IN MOLECULAR PATHOLOGY AND PHARMACOLOGY, vol. 94, no. 2, 1996, pages 115 - 128, XP003006805 * |
RUCKER R. ET AL: "Physiological Importance of Pyrroloquinoline Quinone", VITAMIN, JOURNAL OF THE VITAMIN SOCIETY OF JAPAN, vol. 75, no. 7, 2001, pages 381 - 387, XP002986469 * |
STITES T.E. ET AL: "Dietary deficiency of pyrroloquinoline quinine (PQQ) alters mitochondrial function in young mice", FASEB JOURNAL, vol. 10, no. 3, 1996, pages A800, XP003006804 * |
Cited By (20)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2006117626A (ja) * | 2004-09-24 | 2006-05-11 | Nisshin Pharma Inc | コエンザイムq10配合組成物の製造方法 |
EP2011498A1 (en) * | 2006-04-10 | 2009-01-07 | Mitsubishi Gas Chemical Company, Inc. | Brain function-improving agent, and functional food containing the improving agent |
JPWO2007119588A1 (ja) * | 2006-04-10 | 2009-08-27 | 三菱瓦斯化学株式会社 | 脳機能改善剤及び該改善剤を含有する機能性食品 |
EP2011498A4 (en) * | 2006-04-10 | 2009-11-11 | Mitsubishi Gas Chemical Co | AGENT FOR IMPROVING THE BRAIN FUNCTIONS AND FUNCTIONAL FOOD CONTAINING THE IMPROVING AGENT |
EP2067781A1 (en) * | 2006-09-19 | 2009-06-10 | Kyowa Hakko Bio Co., Ltd. | Agent for improving insulin resistance |
EP2067781A4 (en) * | 2006-09-19 | 2009-12-02 | Kyowa Hakko Bio Co Ltd | AGENT FOR IMPROVING INSULIN RESISTANCE |
US8097635B2 (en) | 2006-09-19 | 2012-01-17 | Kyowa Hakko Bio Co., Ltd. | Insulin resistance improving agent |
CN101578284B (zh) * | 2006-09-19 | 2012-08-15 | 三菱瓦斯化学株式会社 | 胰岛素抵抗改善剂 |
JP2011075851A (ja) * | 2009-09-30 | 2011-04-14 | Sharp Corp | 電子写真感光体およびそれを備えた画像形成装置 |
JP2012001507A (ja) * | 2010-06-18 | 2012-01-05 | Osaka Prefecture Univ | Ptp1b阻害剤及び該阻害剤を含む糖尿病治療薬、皮膚外用剤並びに食品 |
JP2012036094A (ja) * | 2010-08-03 | 2012-02-23 | Mitsubishi Gas Chemical Co Inc | ピロロキノリンキノン含有ソフトカプセル |
WO2012020767A1 (ja) * | 2010-08-09 | 2012-02-16 | 三菱瓦斯化学株式会社 | ピロロキノリンキノンのゲル |
US9012521B2 (en) | 2010-08-09 | 2015-04-21 | Mitsubishi Gas Chemical Company, Inc. | Pyrroloquinoline quinone gel |
JP5884731B2 (ja) * | 2010-08-09 | 2016-03-15 | 三菱瓦斯化学株式会社 | ピロロキノリンキノンのゲル |
JP2015131823A (ja) * | 2015-02-23 | 2015-07-23 | 株式会社ディーエイチシー | Ii型糖尿病治療薬、及び育毛剤 |
JP2018172346A (ja) * | 2017-03-31 | 2018-11-08 | 株式会社東洋新薬 | 妊娠サポート用組成物 |
JP2021529781A (ja) * | 2018-06-26 | 2021-11-04 | リボノバ インコーポレイテッドRibonova Inc. | ミトコンドリア機能障害の治療方法 |
WO2020158415A1 (ja) * | 2019-01-28 | 2020-08-06 | サントリーホールディングス株式会社 | オレキシン受容体拮抗阻害用組成物 |
CN113348019A (zh) * | 2019-01-28 | 2021-09-03 | 三得利控股株式会社 | 食欲素受体拮抗抑制用组合物 |
WO2021132077A1 (ja) * | 2019-12-27 | 2021-07-01 | サントリーホールディングス株式会社 | セサミン類及びpqqを含有する組成物 |
Also Published As
Publication number | Publication date |
---|---|
RU2007111720A (ru) | 2008-10-10 |
US20070259908A1 (en) | 2007-11-08 |
CA2578347A1 (en) | 2006-03-09 |
AU2005278611A1 (en) | 2006-03-09 |
EP1785138A1 (en) | 2007-05-16 |
JPWO2006025247A1 (ja) | 2008-05-08 |
KR20070057218A (ko) | 2007-06-04 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
WO2006025247A1 (ja) | ミトコンドリア賦活剤 | |
US8946303B2 (en) | Fatigue reducing agent | |
EP1897539B1 (en) | Anti-fatigue composition | |
US7708990B2 (en) | Coenzyme Q compositions persisting in blood | |
EP1747778B1 (en) | Anti-fatigue composition | |
WO2005089740A1 (ja) | 血中持続性補酵素q組成物 | |
EP1870095A1 (en) | Composition for increasing anti-oxidation activity in blood | |
EP1987824A1 (en) | Composition for normalizing blood pressure | |
US20090246185A1 (en) | Cardiac dysfunction-ameliorating agent or cardiac function-maintaining agent | |
CN101010081A (zh) | 线粒体激活剂 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
AK | Designated states |
Kind code of ref document: A1 Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BW BY BZ CA CH CN CO CR CU CZ DE DK DM DZ EC EE EG ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KM KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NA NG NI NO NZ OM PG PH PL PT RO RU SC SD SE SG SK SL SM SY TJ TM TN TR TT TZ UA UG US UZ VC VN YU ZA ZM ZW |
|
AL | Designated countries for regional patents |
Kind code of ref document: A1 Designated state(s): GM KE LS MW MZ NA SD SL SZ TZ UG ZM ZW AM AZ BY KG KZ MD RU TJ TM AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IS IT LT LU LV MC NL PL PT RO SE SI SK TR BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG |
|
121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
WWE | Wipo information: entry into national phase |
Ref document number: 2006531967 Country of ref document: JP |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2578347 Country of ref document: CA |
|
WWE | Wipo information: entry into national phase |
Ref document number: 200580028962.7 Country of ref document: CN Ref document number: 725/KOLNP/2007 Country of ref document: IN |
|
NENP | Non-entry into the national phase |
Ref country code: DE |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2005278611 Country of ref document: AU |
|
WWE | Wipo information: entry into national phase |
Ref document number: 11661419 Country of ref document: US |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2005780925 Country of ref document: EP |
|
ENP | Entry into the national phase |
Ref document number: 2005278611 Country of ref document: AU Date of ref document: 20050825 Kind code of ref document: A |
|
WWE | Wipo information: entry into national phase |
Ref document number: 1020077007155 Country of ref document: KR |
|
WWP | Wipo information: published in national office |
Ref document number: 2005278611 Country of ref document: AU |
|
ENP | Entry into the national phase |
Ref document number: 2007111720 Country of ref document: RU Kind code of ref document: A |
|
WWP | Wipo information: published in national office |
Ref document number: 2005780925 Country of ref document: EP |
|
WWP | Wipo information: published in national office |
Ref document number: 11661419 Country of ref document: US |