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WO2014098306A1 - Composition pharmaceutique pour prévenir ou traiter la démence - Google Patents

Composition pharmaceutique pour prévenir ou traiter la démence Download PDF

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Publication number
WO2014098306A1
WO2014098306A1 PCT/KR2013/000578 KR2013000578W WO2014098306A1 WO 2014098306 A1 WO2014098306 A1 WO 2014098306A1 KR 2013000578 W KR2013000578 W KR 2013000578W WO 2014098306 A1 WO2014098306 A1 WO 2014098306A1
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Prior art keywords
dementia
formula
disease
group
compound
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English (en)
Korean (ko)
Inventor
노형준
김금숙
이승은
김승유
홍윤표
이지현
이대영
최재훈
김재윤
최수임
김남식
임성빈
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Korea Rural Development Administration
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Korea Rural Development Administration
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    • 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
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
    • A61K31/343—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide condensed with a carbocyclic ring, e.g. coumaran, bufuralol, befunolol, clobenfurol, amiodarone
    • 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
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/407—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine
    • 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
    • A23L29/00—Foods or foodstuffs containing additives; Preparation or treatment thereof
    • A23L29/03—Organic compounds
    • A23L29/035—Organic compounds containing oxygen as heteroatom
    • 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
    • A23L29/00—Foods or foodstuffs containing additives; Preparation or treatment thereof
    • A23L29/03—Organic compounds
    • A23L29/045—Organic compounds containing nitrogen as heteroatom
    • 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
    • A23L31/00—Edible extracts or preparations of fungi; Preparation or treatment thereof
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
    • 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
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/365—Lactones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/06—Fungi, e.g. yeasts
    • A61K36/07—Basidiomycota, e.g. Cryptococcus
    • 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
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2200/00—Function of food ingredients
    • A23V2200/30—Foods, ingredients or supplements having a functional effect on health
    • A23V2200/322—Foods, ingredients or supplements having a functional effect on health having an effect on the health of the nervous system or on mental function
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2250/00—Food ingredients
    • A23V2250/20—Natural extracts
    • A23V2250/208—Fungi extracts

Definitions

  • the present invention relates to a pharmaceutical composition for preventing or treating dementia comprising a substance extracted from roe deer mushroom as an active ingredient, and more particularly, to a pharmaceutical composition and health functional food including the substance extracted from roe deer mushroom will be.
  • Roe deer mushrooms are called 'dudugo' in China because their mushrooms resemble monkey heads. From summer to autumn, each one grows on the stems of broad-leaved trees such as oak and oak trees. Mushroom shade is about 5 ⁇ 20 cm in diameter, mostly ball-shaped or egg-shaped ball, hairs on the upper side and countless needles hang on the side and bottom. The needle is 1-5cm long and 1mm thick and has a sharp tip.
  • dementia comes from the Latin word meaning "to be demented.” The lack of intellectual ability since birth is called mental retardation. On the other hand, dementia suffers from cognitive function that is deteriorated and overall declines in daily life as the brain function is damaged by various causes. Significant obstacles are appearing.
  • cognitive function refers to various intellectual abilities such as memory, language ability, time and space grasping ability, judgment ability and abstract thinking ability, and each cognitive function is closely related to a specific brain region. There are about 70 disorders that cause clinical syndrome called dementia.
  • Alzheimer's disease and vascular dementia are characterized by various dementia-causing diseases, but the most common are Alzheimer's disease and vascular dementia, but other degenerative brain diseases such as Lewy dementia and Parkinson's disease, normal pressure hydrocephalus, head trauma, brain tumors, metabolic diseases, deficiency diseases, Dementia can be caused by a wide variety of causative diseases, such as addictive diseases and infectious diseases.
  • degenerative brain diseases such as Lewy dementia and Parkinson's disease, normal pressure hydrocephalus, head trauma, brain tumors, metabolic diseases, deficiency diseases, Dementia can be caused by a wide variety of causative diseases, such as addictive diseases and infectious diseases.
  • Acetylcholine is present in the nervous system of animals and is a chemical that transmits nerve impulses to muscles. Such acetylcholine is decomposed into choline and acetic acid by acetylcholinesterase. Therefore, when acetylcholinesterase is excessively activated, acetylcholine, which is an important chemical of neurotransmission, is decomposed and there is a problem that the transmission of nerve stimulation is not smoothed. In addition, the problem caused by the activation of acetylcholinesterase causes neurotransmission problems, which may cause dementia.
  • the problem of the prior art is a variety of causes and diseases of dementia, but the prior art has a problem that there is a lack of raw materials and drugs that effectively treat or prevent it.
  • the activation of acetylcholinesterase may be a cause of dementia, there is a problem in that there is a shortage of raw materials and drugs that can effectively cope with dementia by inhibiting its activity.
  • an object of the present invention is to find a compound that is effective in the prevention and treatment of dementia and to provide a raw material and medicament that can effectively cope with dementia, the acetylcholinesterase By inhibiting the activity to block the cause of dementia, as well as effective in the prevention and treatment of dementia, to provide a substance derived from the locust beetle effective to protect the brain nerve.
  • Acetylcholinesterase activity inhibitor according to a feature of the present invention for solving the above problems comprises at least one compound selected from the group consisting of Formula 1 to 4 or a pharmaceutically acceptable salt thereof as an active ingredient. do.
  • the formula 1 to Formula 4 may be derived from the roe deer mushroom.
  • the inhibitor may include Alzheimer's disease dementia, Vascular dementia, Parkinson's disease dementia, Lewy body dementia, Huntington's disease dementia, and Crutzfeldt. It may act on any one or more diseases selected from the group consisting of Creutzfeldt-Jacob disease type dementia, Pick's disease type dementia, brain tumors, stroke and cognitive impairment.
  • the present invention provides a pharmaceutical composition for preventing or treating dementia comprising at least one compound selected from the group consisting of Formulas 1 to 4 or a pharmaceutically acceptable salt thereof.
  • the present invention also provides a neuroprotective agent comprising at least one compound selected from the group consisting of Formulas 1 to 4 or a pharmaceutically acceptable salt thereof.
  • the health functional food according to another feature of the present invention includes at least one compound selected from the group consisting of Formulas 1 to 4 or a food acceptable salt thereof.
  • Preparation of an acetylcholinesterase activity inhibitor including the compound according to the present invention and an acceptable salt thereof may inhibit the activity of acetylcholinesterase, which is one of the causes of dementia, to effectively cope with the prevention and treatment of dementia. And, it is possible to provide a pharmaceutical composition and health functional food that can protect the brain nerve.
  • FIG. 2 is a graph showing 13 CNMR spectrum analysis results of spectroscopic analysis of Compound 1 of Experimental Example 1.
  • Figure 4 is a graph showing the IR spectrum analysis results of the spectroscopic analysis of the compound 1 of Experimental Example 1.
  • FIG. 6 is a graph showing 13 CNMR spectrum analysis results of spectroscopic analysis of Compound 2 of Experimental Example 1.
  • FIG. 10 is a graph showing 13 CNMR spectrum analysis results of spectroscopic analysis of Compound 3 of Experimental Example 1.
  • FIG. 10 is a graph showing 13 CNMR spectrum analysis results of spectroscopic analysis of Compound 3 of Experimental Example 1.
  • FIG. 14 is a graph showing 13 CNMR spectrum analysis results of spectroscopic analysis of Compound 4 of Experimental Example 1.
  • FIG. 14 is a graph showing 13 CNMR spectrum analysis results of spectroscopic analysis of Compound 4 of Experimental Example 1.
  • 17 is a graph showing the activity inhibitory effect on the acetylcholinesterase of Compounds 1 to 4 and Comparative Example 1 according to the present invention.
  • Acetylcholinesterase is an enzyme that decomposes acetylcholine. If the acetylcholinesterase is activated, acetylcholine may be degraded to interfere with neurotransmission, which may be a cause of dementia.
  • the activity inhibitor of acetylcholinesterase according to the present invention may include at least one compound selected from the group consisting of Formulas 1 to 4 or a pharmaceutically acceptable salt thereof.
  • the compounds of Formulas 1 to 4 may be preferably extracted from the roe deer mushroom.
  • the inhibitor is preferably Alzheimer's disease dementia, Vascular dementia, Parkinson's disease dementia, Lewy body dementia, Huntington's disease dementia, crew It may act on any one or more diseases selected from the group consisting of Creutzfeldt-Jacob disease dementia, Pick's disease dementia, brain tumors, stroke and cognitive impairment.
  • the pharmaceutically acceptable salt thereof may include one or more compounds selected from the group consisting of Chemical Formulas 1 to 4.
  • the invention may also include such agents or salts thereof that are lyophilized and can be reconstituted to form pharmaceutically acceptable formulations for administration, such as by intravenous, intramuscular or subcutaneous injection.
  • at least one compound selected from the group consisting of Formulas 1 to 4 and pharmaceutically acceptable salts thereof described herein can be administered orally or as inhalation as a solid, or intramuscularly as a solution, suspension or emulsion. Or intravenously. More preferably, it may be administered as a liposome suspension by inhalation, intravenous or intramuscularly.
  • a pharmaceutical formulation suitable for administration by inhalation as an aerosol can be provided.
  • the dosage of the activity inhibitor of acetylcholinesterase may be appropriately selected and used depending on symptoms, age, dosage form, etc., preferably, 0.01 to 100 mg per day may be administered once or several times. More preferably, 1 to 80 mg may be administered once or in divided portions.
  • Dementia can be caused by a variety of causes, and inhibiting the activity of acetylcholinesterase, which can be one of the causative agents, can be effective in preventing or treating dementia.
  • another feature of the present invention may be a pharmaceutical composition for preventing or treating dementia comprising at least one compound selected from the group consisting of Chemical Formulas 1 to 4 and a pharmaceutically acceptable salt thereof.
  • the compound of Chemical Formulas 1 to 4 may be extracted from a scab mushroom.
  • the dementia is preferably Alzheimer's disease dementia, Vascular dementia, Parkinson's disease dementia, Lewy body dementia, Huntington's disease dementia, crew At least one selected from the group consisting of Creutzfeldt-Jacob disease dementia and Pick's disease dementia.
  • the Alzheimer's disease dementia is very slowly developed and gradually progresses as a specific dementia.
  • the problem mainly occurs in memory of recent days, and progresses as well as other cognitive declines such as language function and judgment, as well as changes in personality.
  • Psychobehavioral symptoms such as anxiety, depression, delusions, hallucinations, increased aggression, and sleep disorders are often accompanied, and neurological disorders such as stiffness and gait abnormalities or physical complications such as stool incontinence, infection, and pressure sores appear.
  • the vascular dementia is a case in which brain tissue is damaged by cerebrovascular disease and dementia occurs.
  • the vascular dementia is at least one selected from acute onset vascular dementia, multiple infarct dementia, and subcortical vascular dementia.
  • Parkinson's disease dementia is a progressive neurodegenerative disorder characterized by Parkinson's symptoms such as slow movement, trembling at rest, muscle stiffness, dragging and walking and bending posture.
  • Lewy dementia is a memory disorder is not as severe as Alzheimer's disease, judgment judgment, confusion of consciousness is often present and show vision.
  • the chorea dementia is a dementia that occurs as part of extensive degeneration of the brain, and is transmitted by a single autosomal dominant gene. Symptoms are typical of thirty-four teenagers. Progression is slow and usually dies within 10 to 15 years after onset.
  • the Creutzfeldt-Jakob disease dementia is a progressive dementia that is presumed to be caused by a spreadable pathogen and is accompanied by a wide range of neurological signs caused by specific neuropathological changes. The course can be subacute and die within a year.
  • the Pix's disease dementia is a progressive dementia that begins in middle age and is characterized by slowly progressive personality changes and social degeneration, and has disorders of intelligence, memory, and language function accompanied by apathy, morbid pleasure, and sometimes extracorporeal phenomena.
  • the pharmaceutically acceptable salt thereof may include one or more compounds selected from the group consisting of Chemical Formulas 1 to 4.
  • the invention may also include such agents or salts thereof that are lyophilized and can be reconstituted to form pharmaceutically acceptable formulations for administration, such as by intravenous, intramuscular or subcutaneous injection.
  • one or more compounds selected from the group consisting of Formulas 1-4 and pharmaceutically acceptable salts thereof described herein can be administered orally or as inhalations as a solid, or as a solution, suspension or emulsion It can be administered intravenously or intravenously. More preferably, it may be administered as a liposome suspension by inhalation, intravenous or intramuscularly.
  • a pharmaceutical formulation suitable for administration by inhalation as an aerosol can be provided.
  • the dosage of the pharmaceutical composition for preventing or treating dementia may be appropriately selected and used depending on symptoms, age, dosage form, and the like, and preferably, 0.01 to 100 mg per day may be divided once or several times. More preferably, 1 to 80 mg may be administered once or in divided portions.
  • the cranial nerve refers to 12 pairs of motor nerves, sensory nerves, or a mixture of motor and sensory nerves.
  • the first brain nerve corresponds to the sensory nerve as a posterior nerve with respect to smell.
  • the second cranial nerve is also the nerve for seeing as the sensory nerve.
  • the third cranial nerve is a motor nerve and is related to eye movement and pupil contraction.
  • the fourth cranial nerve is the motor nerve, which governs the superior muscle that is involved in eye movement.
  • the fifth cranial nerve is a mixed nerve of the senses and the movement, the motor nerve dominates chewing, the sensory nerve is responsible for the perception of the face, head, ears and the like.
  • the sixth cranial nerve is the motor nerve, which governs the extraocular muscles (external rectus muscles) of the eye between the school and training.
  • the seventh cranial nerve is a mixed nerve of motor and sensory nerves that transmits the taste in the anterior two-thirds of the tongue through facial expression movements that dominate the facial muscles, and the hard nerves, one of the facial nerves. Dominate.
  • Eighth cranial nerve is sensory nerve, cochlear nerve conducts hearing, vestibular nerve conducts positional sense and equilibrium sense.
  • the ninth cranial nerve is a mixed nerve of motor and sensory nerves, distributed in the tongue and pharynx and causes perception, exercise and secretion. It is distributed in the rear muscles of the tongue and the muscles that work and swallow the tongue, and is responsible for the taste.
  • the 10th cranial nerve is a mixed nerve of motor and sensory nerves, which is distributed in the cervix, thorax and abdominal viscera and is an important nerve that controls perception, movement, and secretion.
  • the eleventh cranial nerve is a mixed nerve of motor and sensory nerves that dominates the muscles of the larynx and speaks, and controls the mitral muscles and thoracic vertebral muscles to move the head.
  • the twelfth cranial nerve is a motor neuron, which contracts the muscles of the tongue to speak, and acts as a pure motor neuron with chewing and swallowing.
  • the compounds of Formulas 1 to 4 may be preferably extracted from the roe deer mushroom.
  • the neuroprotective agent may preferably act on any one or more diseases selected from the group consisting of cerebral infarction, stroke, ischemic stroke, cerebral hemorrhage, cerebral edema and cerebrovascular dementia.
  • the cerebral infarction is a disease in which blood vessels of the brain are blocked and necrotic tissue in front of it is necrotic.
  • the stroke refers to a condition in which partial or totally rapid brain function disorder persists for a considerable period of time, and no cause can be found other than cerebrovascular disease.
  • the ischemic stroke is a stroke caused by clogging a cerebrovascular vessel
  • the hemorrhagic stroke is a type of hemorrhagic stroke caused by a bursting cerebrovascular vessel.
  • the brain edema refers to a state in which the volume of brain tissue is increased due to an abnormal increase in the water content in the brain parenchyma.
  • the cerebrovascular dementia is a dementia caused by clogging or bursting blood vessels in the brain region, and unlike Alzheimer's disease, cognitive function is suddenly dropped.
  • the pharmaceutically acceptable salt thereof may include one or more compounds selected from the group consisting of Chemical Formulas 1 to 4.
  • the invention may also include such agents or salts thereof that are lyophilized and can be reconstituted to form pharmaceutically acceptable formulations for administration, such as by intravenous, intramuscular or subcutaneous injection.
  • at least one compound selected from the group consisting of Formulas 1 to 4 and pharmaceutically acceptable salts thereof described herein can be administered orally or as inhalation as a solid, or intramuscularly as a solution, suspension or emulsion. Or intravenously. More preferably, it may be administered as a liposome suspension by inhalation, intravenous or intramuscularly.
  • a pharmaceutical formulation suitable for administration by inhalation as an aerosol can be provided.
  • the dosage of the neuroprotective agent may be appropriately selected and used depending on symptoms, age, dosage form, etc., preferably, 0.01 to 100 mg per day may be administered once or several times. More preferably, 1 to 80 mg may be administered once or in divided portions.
  • the health functional food of the present invention may include at least one compound selected from the group consisting of Chemical Formulas 1 to 4 or a food acceptable salt thereof, and there is no particular limitation on the type of the health functional food.
  • the health functional foods are dairy products including meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gum, ice cream, various soups, beverages, tea, drink, alcoholic beverages and vitamins. And the like, and may be used in the form of pills, powders, granules, acupuncture, tablets, capsules, or beverages, and include all health functional foods in the conventional sense.
  • the health beverage composition of the present invention is not particularly limited to the liquid component except for containing at least one compound selected from the group consisting of Chemical Formulas 1 to 4 or a food acceptable salt thereof, and various flavoring agents as in general beverages.
  • natural carbohydrate or the like as an additional component.
  • natural carbohydrates include monosaccharides such as glucose, fructose and the like; Disaccharides such as maltose, sucrose and the like; Polysaccharides such as dextrin, cyclodextrin; Conventional sugars such as and the like and sugar alcohols such as xylitol, sorbitol, and erythritol.
  • natural flavoring agents tauumatin, stevia extract (e.g., Rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.) can be advantageously used. have.
  • the health functional food of the present invention includes various nutrients, vitamins, minerals (electrolytes), flavors such as synthetic flavors and natural flavors, coloring and neutralizing agents (such as cheese and chocolate), pectic acid and salts thereof, alginic acid And salts thereof, organic acids, protective colloid thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohols, carbonation agents used in carbonated beverages, and the like.
  • the health functional foods of the present invention may contain pulp for the production of natural fruit juices and fruit juice drinks and vegetable drinks. These components can be used independently or in combination.
  • the hexane, methylene chloride, ethyl acetate, butanol fractions obtained in Example 1-2 were obtained by chromatography using a silica gel column. That is, a stepwise concentration gradient solvent system consisting of a hexane-ethyl acetate mixed solvent (99%: 1%, 50%: 50%) and a methylene chloride-methanol mixed solvent (98%: 2%, 50%: 50%)
  • HEH1 to HEH6 9 muskeleton methylene chloride fractions
  • HEM1 to HEE5 5 fractions of ethyl acetate acetate
  • tacrine As a conventional composition for treating dementia, commercially available tacrine (Tacrine) 300nM was used as a comparative example.
  • the molecular weight and molecular formula of the compounds 1 to 4 isolated in Examples 1-4 were determined using LC / MS spectroscopy (manufacturer: Thermo finnigan LCQ decaplus), and through a nuclear magnetic resonance (NMR) analyzer (Verian 500 MHz) 1 H NMR and 13 C NMR spectra were obtained to determine the molecular structure.
  • NMR data were very similar to hericenone J and its spectroscopic results are shown in FIGS. 9-12.
  • Acetylcholinesterase, acetylcholine iodide, 5,5-dithio-bis- (2-nitrobenzoic acid), neostigmine bromine used to measure the activity of acetylcholinesterase Meade (neostigmine bromide) was purchased from Sigma-Aldrich Chemistry Co. and used. Acetylcholinesterase inhibitory activity was measured according to the Elman method (Ellman et al., 1961).
  • mice were extracted and placed in a 10-fold volume of PBS-A (12.5M sodium phosphate buffer pH 7.0, 400 mM NaCl) and pulverized at 500 rpm using a Teflon glass tube, which was centrifuged at 1000 X g for 10 minutes. The supernatant was obtained. PBS-A and Triton X-100 were added to the supernatant, stirred for 30 minutes, and centrifuged at 10000 X g for 10 minutes to obtain an enzyme solution containing acetcholine esterase.
  • PBS-A 12.5M sodium phosphate buffer pH 7.0, 400 mM NaCl
  • Acetylcholinesterase inhibitory ability was calculated by the following equation.
  • tacrine, Comparative Example 1 exhibited 23% inhibitory activity against acetylcholinesterase, but Compounds 1 to 4 of the present invention exhibited higher inhibitory activity than Comparative Example 1, thereby degenerative brain disease. It can be usefully used as a therapeutic substance for phosphorus dementia.
  • Compounds 1 to 4 which are the extracts of the Roestock fungus, according to the present invention, have a high inhibitory effect on acetylcholinesterase activity, and thus inhibit acetylcholinesterase activity, pharmaceutical compositions for preventing or treating dementia, and health functional foods. It is obvious that the material is highly applicable in many fields such as
  • tablets were prepared by tableting according to a conventional method for producing tablets.
  • the capsule was prepared by filling in gelatin capsules according to the conventional method for producing a capsule.
  • composition ratio of the above-mentioned vitamin and mineral mixture is a composition suitable for a relatively healthy food in a preferred manufacturing example, but the composition ratio may be arbitrarily modified, and the above ingredients are mixed according to a general health food manufacturing method.
  • the granules may be prepared and used for preparing a health food composition according to a conventional method.
  • composition ratio is a composition suitable for a preferred beverage in a preferred manufacturing example
  • the composition ratio may be arbitrarily modified according to regional and ethnic preferences such as demand hierarchy, demand country, and usage.

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Abstract

La présente invention concerne un inhibiteur de l'activité de l'acétylcholinestérase, une composition pharmaceutique destinée à prévenir et/ou traiter la démence et/ou un agent neuroprotecteur cérébral qui contien(nen)t un composé dérivé de Hericium erinaceus ou un sel correspondant et/ou un procédé de préparation correspondant.
PCT/KR2013/000578 2012-12-21 2013-01-24 Composition pharmaceutique pour prévenir ou traiter la démence Ceased WO2014098306A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
KR10-2012-0151215 2012-12-21
KR20120151215A KR101509061B1 (ko) 2012-12-21 2012-12-21 노루궁뎅이버섯 유래 물질을 포함하는 치매 예방 또는 치료용 약학적 조성물

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WO2014098306A1 true WO2014098306A1 (fr) 2014-06-26

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CN108912136A (zh) * 2018-08-07 2018-11-30 云南中烟工业有限责任公司 一种具有降刺生津功效的苯并异呋喃酮类化合物、其制备方法及用途
CN108912136B (zh) * 2018-08-07 2020-04-24 云南中烟工业有限责任公司 一种具有降刺生津功效的苯并异呋喃酮类化合物、其制备方法及用途
JP2023506419A (ja) * 2019-12-03 2023-02-16 チュンブク ナショナル ユニバ―シティ インダストリー アカデミック コーオペレーション ファウンデーション イソインドリノン誘導体の調製方法、それに用いられる新規な中間体、及びその調製方法
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