WO2021107585A1 - 오미자 추출물 및 아스코르브산 혼합물을 유효성분으로 함유하는 인지기능, 기억력 및 활동성 증진용 조성물 - Google Patents
오미자 추출물 및 아스코르브산 혼합물을 유효성분으로 함유하는 인지기능, 기억력 및 활동성 증진용 조성물 Download PDFInfo
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- WO2021107585A1 WO2021107585A1 PCT/KR2020/016761 KR2020016761W WO2021107585A1 WO 2021107585 A1 WO2021107585 A1 WO 2021107585A1 KR 2020016761 W KR2020016761 W KR 2020016761W WO 2021107585 A1 WO2021107585 A1 WO 2021107585A1
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- ascorbic acid
- mixture
- memory
- schisandra extract
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Classifications
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- A—HUMAN NECESSITIES
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- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- 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
- A23L33/105—Plant extracts, their artificial duplicates or their derivatives
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- 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
- A23L33/15—Vitamins
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- A—HUMAN NECESSITIES
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- 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
- A61K31/375—Ascorbic acid, i.e. vitamin C; Salts thereof
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- 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
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/79—Schisandraceae (Schisandra family)
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- 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
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
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- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
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- 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
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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Definitions
- the present invention relates to a composition for enhancing cognitive function, memory and activity containing a mixture of omija extract and ascorbic acid as active ingredients.
- brain tissue-related methods may include surgical treatment, drug treatment, or taking a functional substance. Since surgical treatment is not easy, it is recommended to continuously consume drugs or functional substances that are effective in improving memory and lowering memory, focusing on prevention rather than treating diseases that deteriorate memory such as dementia after onset. Therefore, there is a need for development of a method for improving memory by using a naturally-derived substance that has no side effects and can be safely and continuously ingested.
- Korean Patent No. 2023637 discloses a composition for food or feed for improving cognitive function or memory, which includes a desalted tungsten plant extract
- Korean Patent Laid-Open Patent No. No. 2018-0120604 discloses a composition for improving cognition or memory comprising an extract of sagebrush, but with respect to a composition for improving cognitive function, memory and activity containing the Schisandra extract and ascorbic acid mixture of the present invention as active ingredients has not been disclosed
- the present invention was derived from the above needs, and provides a composition for enhancing cognitive function, memory and activity containing a Schisandra extract and a mixture of ascorbic acid as active ingredients, and the mice administered with the Schisandra extract and ascorbic acid mixture
- a composition for enhancing cognitive function, memory and activity containing a Schisandra extract and a mixture of ascorbic acid as active ingredients, and the mice administered with the Schisandra extract and ascorbic acid mixture
- the present invention provides a health functional food composition for enhancing cognitive function, memory and activity containing a Schisandra extract and a mixture of ascorbic acid as active ingredients.
- the present invention provides a pharmaceutical composition for the prevention or treatment of degenerative brain disease, comprising a Schisandra extract and a mixture of ascorbic acid as active ingredients.
- the present invention relates to a composition for improving cognitive function, memory and activity containing a Schisandra extract and a mixture of ascorbic acid as active ingredients, wherein the group administered with the Schisandra extract and ascorbic acid mixture has enhanced memory compared to the group administered with the Schisandra extract or ascorbic acid alone,
- the total movement distance per unit time of the mouse increases, the expression of PSD95 protein in the brain hippocampus, which is involved in the regulation of synaptic plasticity, which is important for improving memory, is significantly increased, and the mitochondrial oxygen consumption in the hippocampus-derived cell line is increased.
- CN is a control group administered by mixing NMP (N-Methyl-2-pyrrolidone) and physiological saline used as a solvent
- SCE+AA is a group administered with a Schisandra extract and ascorbic acid mixture
- SCE is a group administered with a Schisandra extract alone
- AA is ascorbic acid alone.
- *** means that the stiffness of the SCE+AA administration group increased statistically significantly compared to the CN, SCE and AA administration groups, and p ⁇ 0.001.
- CN is a control group administered by mixing NMP (N-Methyl-2-pyrrolidone) and physiological saline used as a solvent
- SCE+AA is a group administered with a Schisandra extract and ascorbic acid mixture
- SCE is a group administered with a Schisandra extract alone
- AA is ascorbic acid alone. * means that the search time for new objects in the SCE+AA administration group increased significantly compared to the CN, SCE and AA administration groups, and p ⁇ 0.05.
- CN is a control group administered by mixing NMP (N-Methyl-2-pyrrolidone) and physiological saline used as a solvent
- SCE+AA is a group administered with a Schisandra extract and ascorbic acid mixture
- SCE is a group administered with a Schisandra extract alone
- AA is ascorbic acid alone.
- *, ** means that the movement of the SCE+AA administration group increased statistically significantly compared to the CN, SCE and AA administration groups, * is p ⁇ 0.05, ** is p ⁇ 0.01.
- CN is a control group administered by mixing NMP (N-Methyl-2-pyrrolidone) and physiological saline used as a solvent
- SCE+AA is a group administered with a Schisandra extract and ascorbic acid mixture
- SCE is a group administered with a Schisandra extract alone
- AA is ascorbic acid alone. ** means that the PSD95 protein content of the SCE+AA administration group increased statistically significantly compared to the CN, SCE and AA administration groups, and ** is p ⁇ 0.01.
- OCR 5 is a result of measuring mitochondrial oxygen consumption rate (OCR) by administering a mixture of Schisandra extract and ascorbic acid in a hippocampal-derived cell line.
- a and B are experimental results of administration of Schisandra extract, ascorbic acid and a mixture thereof
- CN is a control group treated by mixing NMP (N-Methyl-2-pyrrolidone) and physiological saline used as a solvent
- SCE + AA is a group treated with Schisandra extract and ascorbic acid mixture
- SCE is a group treated with Schisandra extract alone
- AA is a group treated with ascorbic acid alone.
- * means that the mitochondrial oxygen consumption of the SCE + AA treatment group was statistically significantly increased compared to the CN treatment group, and * is p ⁇ 0.05.
- C and D are experimental results of administering a mixture according to the mixing ratio of Schisandra extract and ascorbic acid, and Schisandra extract:ascorbic acid was mixed in a weight ratio of 4:1, 2:3 or 1:4.
- * and ** indicate a statistically significant increase in mitochondrial oxygen consumption in the group treated with the Schisandra extract mixed in the 4: 1 weight ratio: ascorbic acid mixture compared to the 2:3 or 1:4 weight ratio mixture: ascorbic acid mixture means, * is p ⁇ 0.05, ** is p ⁇ 0.01.
- One embodiment of the present invention discloses a health functional food composition for enhancing cognitive function, memory and activity containing a Schisandra extract and a mixture of ascorbic acid as active ingredients.
- the solvent of the Schisandra extract may be water, a C1-C4 lower alcohol, or a mixture thereof.
- the Schisandra extract and ascorbic acid mixture may be mixed with Schisandra extract:ascorbic acid in a weight ratio of 3 to 5:1.
- Another embodiment of the present invention discloses a pharmaceutical composition for preventing or treating degenerative brain disease containing a mixture of Schisandra extract and ascorbic acid as active ingredients.
- the degenerative brain disease may be Alzheimer's disease, Parkinson's disease, mild cognitive impairment, meningitis, stroke, dementia, Huntington's disease, or Creutzfeldt-Jakob disease.
- the present invention relates to a health functional food composition for enhancing cognitive function, memory and activity containing a mixture of omija extract and ascorbic acid as active ingredients.
- the solvent of the Schisandra extract may be water, a C1-C4 lower alcohol, or a mixture thereof, preferably ethanol, but is not limited thereto.
- the Schisandra extract and ascorbic acid mixture is preferably mixed Schisandra extract:ascorbic acid in a weight ratio of 3 to 5:1, and more preferably, Schisandra extract:ascorbic acid is mixed in a weight ratio of 4:1, but is not limited thereto.
- the health functional food composition of the present invention When used as a food additive, the health functional food composition may be added as it is or used together with other foods or food ingredients, and may be appropriately used according to a conventional method.
- the amount of the active ingredient may be appropriately used depending on the purpose of its use (prevention or improvement).
- the health functional food composition of the present invention may be added in an amount of 15 parts by weight or less, preferably 10 parts by weight or less, based on the total raw materials.
- the amount may be less than the above range, and since there is no problem in terms of safety, the active ingredient may be used in an amount greater than the above range.
- the type of the health functional food There is no particular limitation on the type of the health functional food.
- foods to which the health functional food composition can be added include meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gum, dairy products including ice cream, various soups, beverages, tea There may be drinks, alcoholic beverages, vitamin complexes, etc., and may include all health foods in a conventional sense.
- the health functional food composition of the present invention may be prepared as a food, particularly a functional food.
- the functional food of the present invention includes ingredients commonly added during food production, and may include, for example, proteins, carbohydrates, fats, nutrients and seasonings.
- ingredients commonly added during food production may include, for example, proteins, carbohydrates, fats, nutrients and seasonings.
- natural carbohydrates or flavoring agents may be included as additional ingredients in addition to the active ingredient.
- the natural carbohydrates include monosaccharides (eg, glucose, fructose, etc.), disaccharides (eg, maltose, sucrose, etc.), oligosaccharides, polysaccharides (eg, dextrin, cyclodextrin, etc.) or sugar alcohols ( For example, xylitol, sorbitol, erythritol, etc.) is preferable.
- natural flavoring agents eg, taumatine, stevia extract, etc.
- synthetic flavoring agents eg, saccharin, aspartame, etc.
- the ratio of these added ingredients is not very important, but is generally selected in the range of 0.01 to 0.1 parts by weight based on 100 parts by weight of the health functional food composition of the present invention.
- the present invention relates to a pharmaceutical composition for the prevention or treatment of degenerative brain diseases containing a mixture of Schisandra extract and ascorbic acid as active ingredients.
- the degenerative brain disease may be Alzheimer's disease, Parkinson's disease, mild cognitive impairment, meningitis, stroke, dementia, Huntington's disease or Creutzfeldt-Jakob disease, preferably dementia or Parkinson's disease, but is not limited thereto.
- composition according to the present invention may be formulated in the form of oral dosage forms such as capsules, powders, granules, tablets, suspensions, emulsions, syrups, aerosols, external preparations, suppositories, and sterile injection solutions according to conventional methods, respectively.
- oral dosage forms such as capsules, powders, granules, tablets, suspensions, emulsions, syrups, aerosols, external preparations, suppositories, and sterile injection solutions according to conventional methods, respectively.
- composition according to the present invention may further include a pharmaceutically acceptable carrier, excipient or diluent.
- Carriers, excipients and diluents that may be included in the pharmaceutical composition of the present invention include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia gum, alginate, gelatin, calcium phosphate, calcium silicate , cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methyl hydroxybenzoate, propyl hydroxybenzoate, talc, magnesium stearate, mineral oil, and the like.
- Solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc., and such solid preparations include at least one excipient in the pharmaceutical composition, for example, starch, calcium carbonate, sucrose or lactose, gelatin, etc. is prepared by mixing
- lubricants such as magnesium stearate and talc may also be used.
- Liquid formulations for oral use include suspensions, internal solutions, emulsions, syrups, etc., and various excipients such as wetting agents, sweetening agents, fragrances, preservatives, etc. in addition to water and liquid paraffin, which are commonly used simple diluents, may be included.
- Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories.
- Non-aqueous solvents and suspending agents include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate.
- Witepsol Macrogol, Tween 61, cacao butter, laurin fat, glycerogelatin, etc. may be used.
- a suitable dosage of the pharmaceutical composition of the present invention may be prescribed variously depending on factors such as formulation method, administration mode, age, weight, sex, pathological condition, food, administration time, administration route, excretion rate and reaction sensitivity of the patient.
- the pharmaceutical composition of the present invention may be administered orally or parenterally, and in the case of parenteral administration, it may be administered by topical application to the skin, intravenous injection, subcutaneous injection, intramuscular injection, intraperitoneal injection, transdermal administration, and the like.
- Schisandra extract was provided by the Korea Plant Extracts Bank, Korea Research Institute of Bioscience and Biotechnology. The extract was specifically pulverized and powdered by the dried plants, and then 1000 ml of 70% (v/v) ethanol was added to 100 g of the powder and extracted at room temperature (20 ⁇ 5° C.) for 72 hours. The extract was obtained from Whatman No. After filtration with 2 filters, the mixture was concentrated using a rotary concentrator at a temperature of 40-50° C., and dried under reduced pressure. The dried Schisandra extract was dissolved in NMP (N-Methyl-2-pyrrolidone, Sigma-Aldrich, MO, USA) solution and administered to mice.
- NMP N-Methyl-2-pyrrolidone
- Ascorbic acid was purchased from Sigma-Aldfich (Sigma-Aldfich, MO, USA) and used.
- C57BL/6 mice were acclimatized by adjusting the illuminance so that day and night were repeated at 12 hour intervals under a temperature condition of 22° C. in an aseptic facility, and the Schisandra extract of the present invention, ascorbic acid (hereinafter, AA) alone, or Schisandra
- AA ascorbic acid
- Schisandra The extract and the AA mixture (4:1 weight ratio) were each injected into the abdominal cavity of an 8-week-old male mouse three times at an interval of 24 hours at 10 mg/kg.
- NMP N-Methyl-2-pyrrolidone, Sigma-Aldrich, MO, USA
- physiological saline were mixed and injected in the same volume as the experimental group. After 3 injections, the following behavioral analysis was performed, respectively.
- each mouse was placed in a 40x40x40cm square box, and the movement for 1 hour was recorded by video. Then, the moving distance was analyzed using EthoVision XT 11.5 software, and the total moving distance was measured and statistically processed.
- a mouse was placed in a fear chamber capable of giving electrical stimulation, and allowed to freely explore the space for 5 minutes. After 5 minutes, a sound of 3 kHz, 80 dB was heard for 20 seconds, and an electric shock (0.4 mA) for 1 second was repeated 3 times at an interval of 1 minute. After 24 hours, the mouse was placed in the same fear chamber and allowed to move freely without any stimulation for 5 minutes. After an additional 24 hours, the mouse was placed in a cylindrical cylinder and allowed to explore the space for 5 minutes, followed by 3 minutes. During the formation of the first fear memory, the same sound was heard and the movement of the mouse was recorded on video. The image was analyzed with freeze frame 4 software, and the percentage of the time that the mouse was immobile without moving was quantified as a percentage.
- the mouse was placed in a cylinder with a diameter of 30 cm and a height of 40 cm installed in the center of two cylinders, and allowed to freely explore objects for 10 minutes. After that, one of the two cylinders was replaced with a square iron pillar, and the movement of the mouse was recorded on video for 10 minutes, so that the time of the mouse turning and looking at, smelling, or touching an object was compared with a familiar object and a new one. All measurements were made on the object and quantitatively compared.
- the hippocampal tissue of the mouse was isolated from the brain and a 10% (w/v) protease inhibitor cocktail (Roche, Basel, Switzerland) containing RIPA buffer [50 mM Tris-HCl pH 7.5, 150 mM NaCl, 0.1% (w/v) SDS, 0.5% (v/v) deoxycholate and 1% (v/v) Nonidet P-40] and crushed. Thereafter, the supernatant was obtained through centrifugation, the protein was quantified, and 12 ⁇ g of the protein was mixed with 5X sample buffer, boiled, and then loaded onto an SDS-PAGE gel for electrophoresis.
- RIPA buffer 50 mM Tris-HCl pH 7.5, 150 mM NaCl, 0.1% (w/v) SDS, 0.5% (v/v) deoxycholate and 1% (v/v) Nonidet P-40
- the protein was transferred to a polyvinylidene fluoride (PVDF) membrane (Millipore, MA, USA), the membrane was blocked with 5% (w/v) skim milk, and then the primary antibody [anti -PSD95 (Thermo Scientific, MA, USA), ⁇ -Tubulin (Sigma-Aldrich, MO, USA) antibody] was added to diluted skim milk and reacted at 4° C. for 16 hours.
- PVDF polyvinylidene fluoride
- the secondary antibody [IgG horseradish peroxidase (HRP) antibody (Pierce Biotechnology, MA, USA)] corresponding to the host of the primary antibody was reacted at room temperature for 1 hour, and then the protein band was analyzed using an ECL system (Thermo Scientific). , MA, USA) was used.
- HRP horseradish peroxidase
- mHippoE-14 cells a mouse hippocampal-derived cell line, were treated with DMEM (Dulbecco's) containing 10% (v/v) FBS (Hyclone, MA, USA), 1% (v/v) penicillin and streptomycin (Hyclone, MA, USA).
- DMEM Dulbecco's
- FBS Hyclone, MA, USA
- penicillin and streptomycin Hyclone, MA, USA
- Modified Eagle's medium Sigma-Aldrich, MO, USA
- Schisandra extract, AA, and a mixture thereof (4:1, w/w) were added to the medium to a concentration of 10 ⁇ g/ml each, Further incubation for 24 hours.
- the basal oxygen consumption rate was measured using an XF24 analyzer (Seahorse, MA, USA), and the ATPase inhibitor oligomycin A (oligomycin A, 20 ⁇ g/ml, Sigma-Aldrich, MO, USA), an oxidative phosphorylation inhibitor as an uncoupler (carbonyl cyanide 3-chlorophenylhydrazone, 50 ⁇ M, Sigma-Aldrich, MO, USA) and mitochondrial respiratory complex I inhibitor rotenone (20 ⁇ M, Sigma-Aldrich) , MO, USA) was sequentially injected and the OCR change was analyzed at 37°C.
- OCR basal oxygen consumption rate
- the movement stop time of the Schisandra extract and the AA mixture group was significantly increased compared to the Schisandra extract alone and the AA alone group. This means that the memory of the mice was improved by the administration of the Schisandra extract and the AA mixture, and the time at which they were still without movement due to the memory of the previous electrical stimulation increased compared to the group treated alone.
- the detection ratio of a new object (Novel) compared to a familiar object (Old) of the Schisandra extract and the AA mixture group was significantly increased compared to the Schisandra extract alone and the AA alone group. This means that when the Schisandra extract and AA mixture were administered, the cognitive function and memory were improved, and the ability to distinguish new objects was improved.
- PSD95 is a synaptic plasticity regulatory protein important for memory enhancement in hippocampal tissues.
- mitochondrial activity in the brain is known to help improve memory. Therefore, mitochondrial activity was confirmed by measuring the oxygen consumption rate of mitochondria in mHippoE-14 cells, a cell line derived from the hippocampus. increased significantly.
- the oxygen consumption rate by the Schisandra extract and the AA mixture mixed in a 4:1 weight ratio of the present invention was 2:3 or It was found to be higher than that of Schisandra extract and AA mixture mixed at a weight ratio of 1:4. Through this, it was confirmed that the Schisandra extract and the AA mixture mixed in a 4:1 weight ratio of the present invention were superior in enhancing mitochondrial activity compared to the Schisandra extract and the AA mixture mixed in other ratios.
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Abstract
Description
Claims (5)
- 오미자 추출물 및 아스코르브산 혼합물을 유효성분으로 함유하는 인지기능, 기억력 및 활동성 증진용 건강기능식품 조성물.
- 제 1 항에 있어서,상기 오미자 추출물의 용매는 물, C1~C4의 저급 알코올 또는 이들의 혼합물인, 인지기능, 기억력 및 활동성 증진용 건강기능식품 조성물.
- 제 1 항에 있어서,상기 오미자 추출물 및 아스코르브산 혼합물은 오미자 추출물:아스코르브산이 3~5:1 중량비로 혼합된 것인 인지기능, 기억력 및 활동성 증진용 건강기능식품 조성물.
- 오미자 추출물 및 아스코르브산 혼합물을 유효성분으로 함유하는 퇴행성 뇌질환의 예방 또는 치료용 약학 조성물.
- 제 4 항에 있어서,상기 퇴행성 뇌질환은 알츠하이머병, 파킨슨병, 경도 인지장애, 뇌막염, 중풍, 치매, 헌팅턴병 또는 크로이츠펠트-야콥병인 것인, 퇴행성 뇌질환 예방 또는 치료용 약학 조성물.
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