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
  • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
  • A61K31/19—Carboxylic acids, e.g. valproic acid
  • A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid 
• • A—HUMAN NECESSITIES
  • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
  • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
  • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
  • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
• • 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
  • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
  • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
  • A61K31/216—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acids having aromatic rings, e.g. benactizyne, clofibrate
• • 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
  • A61P25/26—Psychostimulants, e.g. nicotine, cocaine
• • 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
  • A61P3/02—Nutrients, e.g. vitamins, minerals
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00

Definitions

• the present invention relates to a drug and a food for recovering from fatigue caused by mental activities inherent in humans (eg, computational ability), that is, cerebral fatigue.
• Fatigue is generally roughly classified into mental fatigue and physical fatigue. In modern society, the effects of mental fatigue S are more serious than physical fatigue. Nutritional supplements such as various vitamins and minerals are used as fatigue recovery agents, but the actual purpose is to provide nutrition during physical fatigue. On the other hand, a fatigue recovery agent having an effect on mental fatigue is not yet known.
• Patent Document 2 Japanese Patent Laid-Open No. 2003-261444
• the present invention provides a human cerebral fatigue recovery agent or food for recovery from cerebral fatigue comprising one or more selected from chlorogenic acids, caffeic acid, ferulic acid and their pharmaceutically acceptable salt strength as active ingredients To do.
• the present invention also provides use for producing one or more human cerebral fatigue recovery agents in which chlorogenic acids, caffeic acid, ferulic acid and their pharmaceutically acceptable salt power are also selected.
• the present invention provides a method for recovering human cerebral fatigue characterized by administering one or more effective amounts selected from chlorogenic acids, caffeic acid, ferulic acid and pharmaceutically acceptable salts thereof. It is. Brief Description of Drawings
• FIG. 1 is a graph showing the amount of change in flicker value after taking chlorogenic acids.
• FIG. 2 is a diagram showing the action of chlorogenic acids on fatigue.
• FIG. 3 is a diagram showing the action of chlorogenic acids on active pleasure.
• FIG. 4 is a graph showing the amount of change in flicker value after taking chlorogenic acids.
• FIG. 5 is a graph showing the action of chlorogenic acids on fatigue.
• FIG. 6 is a diagram showing the action of chlorogenic acids on active pleasure.
• FIG. 7 is a diagram showing the action of chlorogenic acids on the alphanumeric character detection task.
• FIG. 8 is a diagram showing the action of chlorogenic acids on the numerical addition task.
• FIG. 9 is a diagram showing the action of chlorogenic acids on short-term memory tasks.
• the present invention provides an agent that recovers fatigue caused by mental activities inherent in humans (for example, computational ability, continuous thinking, etc.), that is, a cerebral fatigue recovery agent.
• the present inventor combines a flicker test that evaluates the degree of cerebral fatigue through visual fatigue and a calculation load task that causes cerebral fatigue, thereby reducing the calculation ability and the like due to continued work, that is, recovering cerebral fatigue.
• a flicker test that evaluates the degree of cerebral fatigue through visual fatigue
• a calculation load task that causes cerebral fatigue, thereby reducing the calculation ability and the like due to continued work, that is, recovering cerebral fatigue.
• the chlorogenic acids, caffeic acid, and ferulic acid used in the present invention can be extracted from natural products containing them, particularly plants, and can be industrially produced by chemical synthesis.
• the chlorogenic acids, caffeic acid, and ferulic acid in the present invention have stereoisomers. In the present invention, pure stereoisomers or a mixture thereof can be used. Specific examples of the chlorogenic acids in the present invention include 3-force fail quinic acid, 4 force fail quinic acid, 5- force fail quinic acid, 3,4-dicafeyl quinic acid, 3,5-dicafe quinic acid, 4, 5— Dicaffeyl quinic acid, 3-ferryl quinic acid, 4-ferryl quinic acid, 5_Hue Norylyl quinic acid and 3-Ferlinoleic acid 4-Fail quinic acid are included (Nakabayashi et al., Chemistry and Technology of Coffee Roasting, Kogaku Publishing Co., Ltd., pl66-167).
• Chlorogenic acids, caffeic acid, and ferulic acid can improve water solubility and increase the physiological effectiveness by making them into salts.
• These salts are pharmaceutically acceptable salts.
• Examples of such basic substances for salt formation include hydroxides of alkali metals such as lithium hydroxide, sodium hydroxide and potassium hydroxide; hydroxides of alkaline earth metals such as magnesium hydroxide and calcium hydroxide. Products; inorganic bases such as ammonium hydroxide, basic amino acids such as arginine, lysine, histidine, ornithine; the ability to use organic bases such as monoethanolamine, diethanolamine, triethanolamine, etc. Earth metal hydroxides are preferred.
• these salts may be prepared and then added to a composition comprising other components, or chlorogenic acids and the like and the salt-forming component may be separately added to the composition. It may be added to form a salt therein.
• Examples of natural product extracts containing chlorogenic acids and caffeic acid include coffee, cabbage, lettuce, arch chalk, tomato, eggplant, potato, carrot, apple, pear, plum, peach and apricot. Extracted from plants such as cherry, sunflower, moloheiya, sweet potato, southern sky leaves, benolee belly, wheat and the like.
• chlorogenic acids are preferably extracted from plants such as green coffee beans, southern sky leaves, and unripe apples. Furthermore, from seeds of coffee arabica LINNE, warm ascorbic acid and quenoic acid are used. Those obtained by extraction with an acidic aqueous solution or hot water are more preferred.
• Natural product extracts containing ferulic acid include, for example, coffee, onion, radish, lemon, sensyu, toki, pine, allen, agi, sweet potato, corn, barley, wheat, Rice is particularly preferred, with rice being preferred.
• the rice in the present invention means raw or dried products such as seeds of Oryza sativa LINNE.
• rice bran oil obtained from rice bran is distributed with water-containing ethanol and hexane under mild alkalinity at room temperature, and then into a water-containing ethanol fraction.
• Examples thereof include a method in which the obtained ferulic acid ester is hydrolyzed with sulfuric acid under heat and purified under pressure.
• a culture solution containing eugenol obtained by purifying bacteria (Pseudomonas) by steam distillation from buds and leaves of Syzygium aromaticum MERRILL et PERRY, or from clove oil. It can also be obtained by culturing and separating and purifying the culture solution.
• Ferulic acid can also be produced by chemical synthesis, for example, by condensation reaction of vanillin and malonic acid (Journal of American Chemical Society, 74, 5346, 1952).
• the human cerebral fatigue recovery agent of the present invention recovers cerebral fatigue based on human mental activity and reduces cerebral fatigue.
• Human mental activity refers to mental activity with human logical understanding. Specific contents of human mental activities include thought work, calculation work, and computer work.
• the above-mentioned cerebral fatigue based on human mental activity varies from person to person, but for personal computer work, etc .: It means the state after 2 hours.
• Cerebral fatigue based on mental activity can be evaluated by performing a flicker test or the like on mental fatigue caused by the Kraepelin test, ATMT, computational load work, or the like.
• the Kraepelin test is a continuous addition task that was originally used for mental examinations. Specifically, it is a task that adds a single digit next to each other in sequence.
• the Kraepelin test can be used for quantification as a model system for computing power, computer work, continuous thinking, and the like.
• ATMT is originally used as a mental function testing method, and it can record the search reaction time for each target in a visual search task by sequentially pressing the target numbers presented on the touch panel.
• the target can be rearranged for each reaction, or a new target can be generated. Therefore, it is possible to measure the working memory and fatigue level during the task.
• the calculation load task gives the subject an alphanumeric detection task, a numerical addition task, and a short-term memory task.
• the alpha-numeric detection task is a task where the mouse is left-clicked when a fixed number or letter is presented, and right-click otherwise.
• the number addition task is a task to input the value obtained by adding all the two-digit and two-stage numbers presented from the keyboard.
• the short-term memory task is a task that left-clicks when a number that matches the first four numbers presented on the left side is presented on the right side, and right-clicks when they do not match. It can be positioned as cerebral fatigue generation work based on activity work.
• the flicker test is a method for measuring the visual response to a light source flashing at an arbitrary interval, and directly evaluates the activity state (fatigue state) of the cerebral cortex through a visual instrument.
• a flicker test is performed.
• fingertip volume pulse wave measurement (chaos analysis)
• Fingertip volume pulse wave measurement (chaos analysis) can quantify the state of the whole body from the fingertip because the pulse dynamics are chaotic. Chaos is caused by the entanglement of multiple chaos, and has the characteristic of forming one chaos locally. Therefore, if an analysis using this theory is performed, it is considered that the state of the whole body can be grasped as a numerical value based on information from only a part of the body.
• the fatigue recovery effect of the present invention is that the decrease in flicker test value, which is indicated as mental fatigue (cerebral fatigue), is recovered and reduced by ingestion of chlorogenic acids and the like.
• the cerebral fatigue that can be recovered with the human cerebral fatigue recovery agent of the present invention is fatigue based mainly on desk work or the like that is performed by a human at work or study.
• the chlorogenic acids and the like which are active ingredients of the human cerebral fatigue recovery agent of the present invention, may be taken as they are, but are preferably shaped in the form of a pharmaceutically acceptable salt, for example, hydrochloride.
• auxiliary ingredients commonly used in the pharmaceutical and food fields such as pharmaceuticals and carriers, such as lactose, sucrose, liquid sugar, honey, magnesium stearate, oxypropylcellulose, various vitamins, citrate, It can be made into capsules, tablets, powders, granules, drinks, injections, infusions, etc. along with ingoic acid, fragrances, inorganic salts and the like.
• the food is preferably a green tea beverage, oolong tea beverage, tea beverage, coffee beverage, or isotonic beverage.
• the human cerebral fatigue recovery agent and cerebral fatigue recovery food of the present invention are useful for recovery of decreased cerebral function such as a decrease in computational ability based mainly on computer use, and the dosage is 1 for adults.
• Chlorogenic acids, caffeic acid, ferulic acid or their pharmaceutically acceptable salts per day are preferably 30 to 14000 mg, more preferably 50 to 10000 mg, still more preferably 200 to 7600 mg, and particularly preferably 250 to 3000 mg.
• the food for recovering human cerebral fatigue of the present invention can be displayed to those who feel cerebral fatigue, to recover from a decrease in cerebral function, and the like.
• a subjective questionnaire is a questionnaire to measure the subjective state of multiple emotions at the same time, including depression (anxiety, anxiety, concerned, unconfident, clever), fatigue (boring, tired) Boring, sluggish, lethargic, active pleasure (lively, energetic, energetic, energetic, cheerful), inactive pleasure (slow, laid-back, ideac) 4) (1. I don't feel at all) How much do you feel about 5 items, that is, Naughty, Careful, Careful, Concentration (Careful, Careful, Careful, Thoughtful, Careful) , 2. I don't feel much, 3. I feel a little, 4. I feel it clearly).
• raw coffee bean extract (chlorogenic acids 600mg, ingredient; chlorogenic acids 47.9%, caffeine 1.1%) powder 1.25g or placebo 644mg (component; chlorogenic acids 0.8) (%, Force Fein 0%) was divided into 5 oblates, drunk with 190 mL of water, and the flicker test was performed again.
• a subjective questionnaire before and after drinking Sampnore I heard a feeling of fatigue at the time.
• 15 minutes, 30 minutes, 60 minutes, 90 minutes, and 120 minutes after using a coffee beans extract or placebo containing chlorogenic acid as the main component Flicker test computational load work, flicker test, subjective questionnaire The flicker test and the change of the subjective questionnaire score after the calculation load work at each time were evaluated.
• Subjective questionnaires are questionnaires that measure the subjective state of multiple emotions at the same time. Depression, anxiety (powerfulness, anxiety, concerned, unconfident, clever), fatigue (boring, Tired, boring, sluggish, lethargic, active pleasure (lively, energetic, energetic, energetic, cheerful), inactive pleasure (relaxed, laid-back, How much do you feel about five items, i.e., Outlook, tranquil, carefree, concentration (careful, careful, polite, thoughtful, careful), 4 levels (1. (3) I feel a little, (4) I feel it clearly).

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• 2005
  • 2005-02-24 JP JP2005048198A patent/JP2006160721A/ja not_active Withdrawn
  • 2005-11-08 US US11/718,894 patent/US20070270497A1/en not_active Abandoned
  • 2005-11-08 WO PCT/JP2005/020432 patent/WO2006051773A1/ja not_active Ceased
  • 2005-11-08 EP EP05806145A patent/EP1810671A4/en not_active Withdrawn
  • 2005-11-08 KR KR1020077010085A patent/KR20070083944A/ko not_active Withdrawn
  • 2005-11-09 TW TW094139278A patent/TW200621281A/zh unknown
• 2009
  • 2009-06-29 US US12/493,605 patent/US20090264524A1/en not_active Abandoned

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