WO2021020912A1 - Utilisation d'une composition pour la prévention, l'amélioration ou le traitement d'un dysfonctionnement cognitif comprenant un extrait de racine de polygonum cuspidata et de cinnamomum cassia - Google Patents
Utilisation d'une composition pour la prévention, l'amélioration ou le traitement d'un dysfonctionnement cognitif comprenant un extrait de racine de polygonum cuspidata et de cinnamomum cassia Download PDFInfo
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Classifications
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- 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
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/70—Polygonaceae (Buckwheat family), e.g. spineflower or dock
- A61K36/704—Polygonum, e.g. knotweed
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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
- A23L33/105—Plant extracts, their artificial duplicates or their derivatives
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- 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
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/54—Lauraceae (Laurel family), e.g. cinnamon or sassafras
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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
-
- 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
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
-
- 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
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- 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 the use of a composition comprising an extract of prickly pear and prickly pear for the prevention, improvement or treatment of cognitive dysfunction.
- Cognition refers to the whole process of thinking, speaking, remembering, judging and executing with the brain in human life. Therefore,'cognitive function' includes attention, perception, memory, language ability, and executive ability, and'cognitive function disorder' is the most prominent phenomenon among aging phenomena in the brain, characterized by a decrease in learning and memory ability, and a decrease in judgment ability. It is a physiological phenomenon that gets erased. In particular, these cognitive dysfunctions can appear in a variety of ways. Among them, dementia significantly interferes with interpersonal relationships, occupational functions, and daily life functions due to a decrease in cognitive functions such as memory, language abilities, visual perception and spatio-temporal composition abilities, and executive functions. It is diagnosed as a complex disease that causes this.
- Alzheimer's dementia accounts for the majority of senile dementia.
- Alzheimer's dementia is commonly called Alzheimer's disease (AD), and it can be said to be a disease that slowly dies without any treatment efforts.
- AD Alzheimer's disease
- AD neuronal cell death due to inflammatory reactions including oxidative stress caused by A ⁇ deposited on the brain parenchyma and cerebrovascular wall is the most important in the pathogenesis of AD. It is known to play a role, and ⁇ and ⁇ -secretase are largely involved in the production of A ⁇ , and studies on ⁇ and ⁇ -secretase activity inhibitors that can reduce the production of A ⁇ are drawing attention. Therefore, for the prevention and treatment of AD, studies related to the prevention and treatment of AD are being conducted through the identification of various targets and mechanisms of action, and recently, studies on the development of functional materials for removing A ⁇ are being made most actively.
- Acetylcholinesterase inhibitors (Acricept, Reminyl, Exelon) that increase the amount of choline are attracting attention.
- tacrine product name Cognex Capsule
- donepezil product name Aricept
- AD treatments including these drugs have reported serious side effects.
- Tecrine has symptoms such as hepatotoxicity, insomnia, gastrointestinal disorders, confusion, anorexia and nervousness, and donepezil has muscle cramps, fatigue, insomnia, dizziness, It is known that disorders of the mental and nervous system such as nightmares and vivid dreams, and disorders of the digestive system such as diarrhea, nausea, vomiting, etc.
- these drugs may be effective in temporarily alleviating the symptoms of AD, but a treatment and treatment that can fundamentally treat AD have not been developed until now.
- polygonum cuspidatum Sieb. et Zucc. Reynoutria japonica Hou.
- a perennial herbaceous plant belonging to the Mardiaceae family refers to the roots or rhizomes of plants of the genus and related plants.
- Hojanggeun is distributed in Korea, Japan, Taiwan, and China, and in Korea, it grows in valleys across the country.
- the rhizome is more than 1m high, and the rhizome extends sideways from the basement, is woody, yellowish brown, and has a clear node.
- the stem grows straight and is hollow in a circular shape. There are no hairs on the surface and there are many red or purple spots. These roots, rhizomes and leaves have been used as medicinal materials from ancient times. Hojanggeun is known as palliative, diuretic, tonggyeong, and antitussive tablets, and has antibacterial and antiviral pharmacological effects.
- Cinnamomum cassia Blume an evergreen tree belonging to the camphor family, is the stem bark of broilers or other similar plants, with the perilla and primary cortex removed. It is a long plank-shaped or cylindrical shape, and the length is 10-20cm, and the thickness is uneven. Both the outer and inner sides are reddish brown, and the quality is well broken. The bent side is reddish brown and rich in oil. It has a unique aroma and tastes spicy and sweet.
- the pharmacological action of Gyesim is a cardiovascular agent that promotes blood circulation and is known to be good for heart breakdown, excitement, dry stomach suit, warmth health, whole meridians, positive position, body temperature control, improvement of weak constitution, and gustular wind.
- the present inventors confirmed that the complex extract of Hojanggeun and Gyesim showed a synergistic effect in improving cognitive dysfunction significantly better than each single extract, and completed the present invention.
- Patent Document 1 Korean Patent Publication No. 10-2019-0047359
- Another object of the present invention is to provide a health functional food composition for the prevention or improvement of cognitive dysfunction comprising the extract of janggeun and geunsim.
- Another object of the present invention is to provide a health functional food composition for enhancing learning ability or memory, comprising the extract of Hojanggeun and Gyesim.
- Another object of the present invention is to provide a composition for improving cognitive function lowering, including the extract of Hojanggeun and Gyesim.
- Another object of the present invention is to provide a method for enhancing learning ability or memory, comprising administering to an individual in need thereof in an effective amount a composition comprising a ginseng root and ginseng extract.
- Another object of the present invention is to provide a method for preventing or treating cognitive decline, or a method for improving cognitive function, comprising administering to an individual in need thereof in an effective amount a composition comprising a ginseng root extract and a ginseng extract.
- composition comprising a prickly pear extract and a prickly pear extract in the manufacture of a drug and/or a functional food for preventing or treating cognitive dysfunction.
- Another object of the present invention is to provide a use of a composition comprising a ginseng root and ginseng extract in the manufacture of a drug and/or a functional food for enhancing learning ability or memory.
- Another object of the present invention is to provide a use of a composition comprising a prickly pear extract and prickly pear extract in the manufacture of a drug and/or a functional food for the prevention or treatment of cognitive decline or improvement of cognitive function.
- the present invention provides a pharmaceutical composition for the prevention or treatment of cognitive dysfunction comprising the extract of Hojanggeun and Gyesim in the first aspect.
- the present invention provides a health functional food composition for the prevention or improvement of cognitive dysfunction comprising the extract of janggeun and geunsim.
- the present invention provides a health functional food composition for improving learning ability or memory, including the extract of janggeun and geunsim.
- the present invention provides a composition for improving cognitive function lowering, including the extract of janggeun and geunsim.
- the present invention provides a method for preventing or treating cognitive dysfunction, comprising administering to an individual in need thereof in an effective amount of a composition comprising an extract of Giliworm root and Pillaris.
- the present invention provides a method for improving learning ability or memory, comprising administering to an individual in need thereof in an effective amount a composition comprising a ginseng root and ginseng extract.
- the present invention provides a method for preventing or treating cognitive decline, or a method for improving cognitive function, comprising administering to an individual in need thereof in an effective amount of a composition comprising an extract of prickly pear.
- the present invention provides a use of a composition comprising a prickly pear extract and a prickly pear extract in the manufacture of a pharmaceutical and/or functional food for preventing or treating cognitive dysfunction.
- the present invention provides a use of a composition comprising the extract of ginseng root and prickly pear in the manufacture of a drug and/or functional food for enhancing learning ability or memory.
- the present invention provides a use of a composition comprising a ginseng root and prickly pear extract in the manufacture of a drug and/or a functional food for preventing or treating cognitive decline or improving cognitive function.
- the extracts of jangeun and ginseng can be extracted using water, C1 to C4 lower alcohols, or a mixture thereof as a solvent.
- the extract of jangjanggeun and ginseng root may be mixed in a weight ratio of greater than 1:0.5 to less than 1:2.
- the cognitive dysfunction is dementia, Alzheimer's, Huntington's disease, vascular dementia, ischemic stroke, traumatic brain injury, forgetfulness, Parkinson's disease, Pick disease, Creutzfeldt's disease (Creutzfeldt's disease).
- -Jakob disease and mild cognitive dysfunction may be any one or more selected from the group consisting of.
- the cognitive decline may be any one or more selected from the group consisting of lethargy, attention loss, depression, hearing loss, painlessness, inactivity and discrimination.
- the composition for improving cognitive decline may be a pharmaceutical or food composition.
- composition comprising the complex extracts of Hojanggeun and Gyesim of the present invention effectively inhibits neuroinflammation, significantly reduces the level of MCP-1, a blood biomarker that affects cognitive function, and significantly inhibits systemic inflammation. And, it was found to enhance cognitive function, learning ability and/or memory in an animal model of dementia induced by scopolamine. Therefore, it can be applied in various ways to prevent, improve or treat cognitive decline, prevent, improve or treat cognitive dysfunction or neuroinflammation, as well as improving memory and learning ability of test takers or office workers who require high-level brain activity. have.
- FIG. 2 is a graph confirming the effect of reducing neuroinflammation according to the weight ratio of a mixture of gaujang muscle and gypsy in BV2 cells in which an inflammatory response was induced through IL-10 gene expression analysis.
- IL-1 ⁇ various inflammatory factors
- IL-10 various inflammatory factors
- iNOS various inflammatory factors
- FIG. 4 is a graph showing the effect of reducing the level of MCP-1 in blood according to administration of a complex extract of Hojanggeun and Gyesim.
- FIG. 5 is a graph showing the effect of reducing the level of TNF- ⁇ in the blood according to administration of a complex extract of Hojanggeun and Gyesim.
- FIG. 6 is a graph showing the effect of reducing IL-6 levels in blood according to administration of a complex extract of Hojanggeun and Gyesim.
- FIG. 7 is a graph showing the results of measuring the effect of improving cognitive and short-term memory according to the administration of a complex extract of Gaujanggeun and Gyesim by a Y-maze cross-behavior (Spontaneous alternation) experiment.
- Figure 8 is a graph confirming the change in the number of movements to the entire arm (arm) according to the administration of the complex extract of geunjanggeun and geunsim in the Y-type maze experiment.
- FIG. 9 is a graph showing the results of measuring the learning and long-term memory improvement effect according to the administration of a complex extract of jangjanggeun and geunsim (Passive avoidance) experiment.
- the existing drugs used for the treatment of cognitive dysfunction are only effective in temporarily alleviating AD symptoms, but have fundamental limitations in treating AD, and various side effects caused by these drugs have been reported.
- the present inventors confirmed that the complex extracts of Hojanggeun and Kyesim show a synergistic effect on improving cognitive dysfunction significantly better than each single extract, and the prevention of cognitive dysfunction by using the complex extract of Hojanggeun and Kyesim , By providing a composition for improvement or treatment, a solution to the above-described problem was sought.
- composition comprising the complex extracts of Hojanggeun and Gyesim of the present invention effectively inhibits neuroinflammation, significantly reduces the level of MCP-1, a blood biomarker that affects cognitive function, and significantly inhibits systemic inflammation. And, it was found to enhance cognitive function, learning ability and/or memory in an animal model of dementia induced by scopolamine. Therefore, the prevention, improvement or treatment of cognitive decline, as well as pharmaceutical and food compositions for enhancing memory and learning ability of students or office workers who require high-level brain activity, prevention, improvement or treatment of cognitive dysfunction or neuroinflammation It can be applied in a variety of pharmaceutical and food compositions for.
- a first aspect of the present invention relates to a composition showing a positive or beneficial effect on cognitive dysfunction, learning ability, memory, and/or cognitive function, comprising the extracts of chinensis and prickly pear as active ingredients.
- the present invention provides a pharmaceutical composition for the prevention or treatment of cognitive dysfunction, comprising the extract of janggeun and geunsim.
- the present invention provides a health functional food composition for the prevention or improvement of cognitive dysfunction comprising the extract of janggeun and geunsim.
- the present invention provides a health functional food composition for improving learning ability or memory, including the extract of janggeun and geunsim.
- the present invention provides a composition for improving cognitive function lowering, including the extract of janggeun and geunsim.
- the hojanggeun and chicken syrup may be purchased and used commercially, or may be directly collected or cultivated in nature.
- the root for example, the root, the upper part, the stem, the leaf, the flower, the trunk of the fruit, the fruit It can be extracted from the skin as well as plant tissue culture.
- composition of the present invention may be prepared in the form of extracting by mixing a single extract of jangjanggeun and chicken shim respectively at a specific weight ratio, or mixing a jangchim and chicken shim at a specific weight ratio, and mixing mentioned in the present invention
- the weight ratio refers to both the mixed weight ratio of each single extract and the mixed weight ratio of the raw material before the extract is prepared.
- Gaujanggeun and chicken core can be used after washing and drying to remove foreign substances, and pulverized to increase extraction efficiency.
- the method of preparing the complex extract of the root janggeun and gyesim may use conventional extraction methods in the art such as immersion extraction, static extraction, ultrasonic extraction, filtration, hot water extraction, and reflux extraction.
- the extraction solvent may be used without limitation as long as it is a conventional extraction solvent in the art, preferably water, C1 ⁇ C4 alcohol, or a mixed solvent thereof, more preferably water, methanol or ethanol, and most Preferably, it may be ethanol.
- the extraction solvent can be extracted by adding 1 to 20 times the weight of the ginseng root and chicken core.
- the extraction time may be 0.5 to 48 hours, more preferably 1 to 36 hours, but is not limited thereto, and the number of extractions may be repeated once to 10 times.
- the concentration may be concentrated under reduced pressure, and the concentration under reduced pressure may be performed using a vacuum vacuum concentrator or a vacuum rotary evaporator, but is not limited thereto.
- the drying is preferably vacuum drying, vacuum drying, boiling drying, spray drying, or freeze drying, but is not limited thereto.
- extract refers to a liquid component obtained by immersing a target substance in various solvents and then extracting at room temperature, low temperature, or warm state for a certain period of time, and removing the solvent from the liquid component. It means the result of obtained solid content etc.
- it can be comprehensively interpreted as including all of the diluted solution of the resultant, the concentrate thereof, the preparation thereof, and the purified product.
- the extract of jangchim root and ginseng extract may be mixed in an optimal weight ratio to induce the most excellent synergistic effect, for example, a weight ratio of greater than 1:0.5 to less than 1:2, most preferably 1 It can be mixed in a :1 weight ratio.
- a weight ratio of greater than 1:0.5 to less than 1:2, most preferably 1 It can be mixed in a :1 weight ratio.
- the combined synergistic effect is reduced and thus the optimal activity cannot be exhibited. Therefore, it is preferable to mix the extracts between the roots and branches in the weight ratio.
- one single extract is not mixed in a weight exceeding 2 times that of the other single extract. It is most preferably mixed.
- cognitive dysfunction refers to mental and behavioral disorders and endocrine disorders, metabolic and nutritional disorders, and memory declines due to drugs, etc. due to brain diseases, brain injury, addiction, etc. Includes memory impairment.
- Cognitive disorders in the present invention include dementia, Alzheimer's, Huntington's disease, vascular dementia, ischemic stroke, traumatic brain injury, forgetfulness, Parkinson's disease, Pick disease, Creutzfeldt-Jakob disease, and mild cognitive function. It may be any one or more selected from among the disorders, but is not limited thereto.
- the mild cognitive dysfunction is defined as a pre-dementia clinical stage in which memory and cognitive functions are significantly lowered compared to age and educational level, but does not cause any disturbance in life.
- the cognitive dysfunction includes symptoms of brain function abnormalities such as memory loss and dementia, which are caused by estrogen reduction in menopausal women.
- estrogen is associated with neurodegeneration of the hippocampus, which is the center of memory and cognitive function, and causes cognitive impairment.
- the hippocampus stores short-term memory and transmits information to the cerebral cortex, limbic system, and hypothalamus in order to convert to long-term memory.
- the decrease in estrogen due to menopause deteriorates language memory, learning ability, and fine movement skills.
- Gramy CL Functional brain imaging and age-related changes in cognition. Biological Psychology. 2000;54(1-3):259-81).
- MCP-1 is a type of cytokine secreted by monocytes, macrophages, and dendritic cells, and plays a role in bringing monocytes, memory T cells, and dendritic cells to the site of inflammation. Because it mediates the inflammatory response, the mechanism related to inflammation is mainly known, but a new function as a blood factor regulating cognitive function was reported in 2010, and it has established itself as a marker for cognitive function in blood. According to reports that MCP-1 is increased in the blood of menopausal animal models of OVX (OVX) animals and that memory and cognitive declines are caused by OVX (Kim WK et al.
- OVX menopausal animal models of OVX
- Monocyte Chemoattractant Protein-1 Deficiency Attenuates Oxidative Stress and Protects against Ovariectomy-Induced Chronic Inflammation in Mice.PLoS One. 2013;8(8):e72108; Su J et al.
- the International Journal of neuroscience. 2012;122(10):549-59) it can be seen that there is a possibility that the level of MCP-1 in the blood increased by OVX and the decline in memory and cognitive function are largely related.
- neuroinflammation refers to inflammation occurring in the brain, and is an important factor causing cognitive disorder-related diseases. It is known that excessive activation of inflammatory cells in the brain leads to increased secretion of inflammatory cytokines, and cognitive impairment is caused by damage to brain cells by overactivation of this brain inflammatory response.
- cogntive function decline may be any one or more selected from the group consisting of lethargy, memory loss, forgetfulness, cognitive decline, learning disability, attention loss, depression, hearing loss, painlessness, inactivity and discrimination. have.
- the complex extract of Hojanggeun and Gyesim significantly reduces the level of MCP-1, a blood biomarker that affects cognitive function, and as shown in Figs. 5 and 6, TNF- ⁇ and IL in the blood
- TNF- ⁇ and IL TNF- ⁇ and IL in the blood
- Figs. 7 to 9 TNF- ⁇ and IL in the blood
- Figs. 7 to 9 TNF- ⁇ and IL in the blood
- it shows the effect of improving cognitive function, learning ability, or memory, which is lowered by anticholinergic drugs. It may be used as a therapeutic agent or food for prevention, improvement or treatment and/or improvement of learning ability or memory, prevention, improvement or treatment of cognitive decline.
- prevention means any action that inhibits or delays the onset of a disease or condition. In the present invention, it means to delay the onset of or suppress the onset of cognitive dysfunction.
- the term "improvement” refers to any action that improves or beneficially changes a disease or condition, and in the present invention, improves symptoms of cognitive dysfunction or improves cognitive function, learning ability, or memory. It means letting go.
- treatment refers to any action that delays, stops, or reverses the progression of a disease or condition, and in the present invention, cognitive dysfunction or symptoms of cognitive function, learning ability, or memory decline It means to alleviate, alleviate or eliminate, or reverse.
- the term "synergy effect” refers to the effect that occurs when each component is administered in combination (combination) is greater than the sum of the effects that occur when administered alone as a single component [Chou and Talalay, Adv. Enzyme. Regul., 22:27-55, 1984].
- the complex extract of Hojanggeun and Gyesim of the present invention increases the effect of preventing, improving or treating cognitive dysfunction than each single extract, and also increases the effect of enhancing cognitive function, learning ability or memory.
- administered in combination means that an extract or ingredient is administered together to a patient. That each extract or component is administered together means that each component can be administered at the same time or in any order or sequentially at different times in order to obtain the desired therapeutic effect.
- patient refers to any single individual in need of treatment, including humans, cattle, dogs, guinea pigs, rabbits, chickens, insects, and the like.
- any subject who participated in a clinical study trial showing no clinical manifestation of any disease, or a subject who participated in an epidemiological study or a subject used as a control group is included.
- composition for improving cognitive function reduction of the present invention may be used as a pharmaceutical and/or food composition.
- the pharmaceutical composition of the present invention can be administered to mammals including humans by any method.
- it can be administered orally or parenterally, and parenteral administration methods are not limited thereto, but intravenous, intramuscular, intraarterial, intramedullary, intrathecal, intracardiac, transdermal, subcutaneous, intraperitoneal , Intranasal, intestinal, topical, sublingual or rectal administration.
- the pharmaceutical composition of the present invention can be formulated as a formulation for oral administration or parenteral administration according to the route of administration as described above.
- one or more buffers e.g., saline or PBS
- carbohydrates e.g., glucose, mannose, sucrose, or dextran, etc.
- antioxidants e.g., bacteriostatic agents, chelating agents (e.g., EDTA) Or glutathione
- fillers e.g., extenders, binders, adjuvants (e.g., aluminum hydroxide), suspending agents, thickening agents, wetting agents, disintegrants or surfactants, diluents or excipients.
- adjuvants e.g., aluminum hydroxide
- suspending agents thickening agents, wetting agents, disintegrants or surfactants, diluents or excipients.
- Solid preparations for oral administration include tablets, pills, powders, granules, liquids, gels, syrups, slurries, suspensions or capsules, and the like, and such solid preparations are at least one excipient in the pharmaceutical composition of the present invention, for example , Starch (including corn starch, wheat starch, rice starch, potato starch, etc.), Calcium carbonate, Sucrose, Lactose, Dextrose, Sorbitol, Mannitol, Xylitol, Erythritol Maltitol, Cellulose , Methyl cellulose, sodium carboxymethylcellulose, and hydroxypropylmethyl-cellulose or gelatin may be mixed and prepared.
- tablets or dragees can be obtained by blending the active ingredient with a solid excipient, pulverizing it, adding a suitable auxiliary, and processing into a granule mixture.
- Liquid preparations for oral use include suspensions, liquid solutions, emulsions, or syrups, but may include various excipients, such as wetting agents, sweetening agents, fragrances, or preservatives, in addition to water or liquid paraffin, which are simple diluents commonly used. .
- cross-linked polyvinylpyrrolidone, agar, alginic acid, or sodium alginate may be added as a disintegrant, and an anti-coagulant, a lubricant, a wetting agent, a fragrance, an emulsifier and a preservative may be additionally included.
- the pharmaceutical composition of the present invention may be formulated according to a method known in the art in the form of an injection, a transdermal administration, and a nasal inhalation agent together with a suitable parenteral carrier.
- a suitable parenteral carrier In the case of such injections, they must be sterilized and protected from contamination by microorganisms such as bacteria and fungi.
- suitable carriers for injections include, but are not limited to, water, ethanol, polyol (eg, glycerol, propylene glycol and liquid polyethylene glycol, etc.), a mixture thereof and/or a solvent or dispersion medium containing vegetable oil. I can.
- suitable carriers include isotonic solutions such as Hanks' solution, Ringer's solution, phosphate buffered saline (PBS) containing triethanolamine or sterile water for injection, 10% ethanol, 40% propylene glycol and 5% dextrose. Etc. can be used.
- PBS phosphate buffered saline
- various antibacterial and antifungal agents such as paraben, chlorobutanol, phenol, sorbic acid, thimerosal, and the like may be additionally included.
- the injection may further include an isotonic agent such as sugar or sodium chloride in most cases.
- transdermal administration In the case of transdermal administration, ointments, creams, lotions, gels, external solutions, pasta, liniment, and air rolls are included.
- transdermal administration' means that the active ingredient in an effective amount contained in the pharmaceutical composition is delivered into the skin by topically administering the pharmaceutical composition to the skin.
- the compounds used according to the invention can be prepared using a suitable propellant, for example dichlorofluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane, carbon dioxide or other suitable gas, pressurized pack or It can be conveniently delivered from a nebulizer in the form of an aerosol spray.
- a pressurized aerosol the dosage unit can be determined by providing a valve that delivers a metered amount.
- gelatin capsules and cartridges for use in an inhaler or insufflator can be formulated to contain a powder mixture of the compound and a suitable powder base such as lactose or starch. Formulations for parenteral administration are described in Remington's Pharmaceutical Science, 15th Edition, 1975. Mack Publishing Company, Easton, Pennsylvania 18042, Chapter 87: Blaug, Seymour, a formula generally known for all pharmaceutical chemistry.
- the pharmaceutical composition of the present invention may provide a desirable effect of preventing, improving or treating cognitive impairment and/or enhancing learning ability or memory when it contains the complex extract of Hojanggeun and Gisim in an effective amount.
- the term "effective amount" refers to an amount that exhibits a higher response compared to the negative control group, and preferably refers to an amount sufficient to prevent, ameliorate or treat cognitive dysfunction.
- the complex extract of Hojanggeun and Gyesim may be contained in 0.01 to 99.9%, and the remaining amount may be occupied by a pharmaceutically acceptable carrier.
- the effective amount of the complex extract of Hojanggeun and Gyesim contained in the pharmaceutical composition of the present invention will vary depending on the form in which the composition is commercialized.
- the total effective amount of the pharmaceutical composition of the present invention may be administered to a patient in a single dose, and may be administered by a fractionated treatment protocol that is administered for a long time in multiple doses.
- the pharmaceutical composition of the present invention may vary the content of the active ingredient depending on the severity of the disease. For example, it may be administered in divided doses from 1 to several times so as to be administered in an amount of preferably 0.001 to 100 mg, more preferably 0.01 to 10 mg per 1 kg of body weight per day, based on the complex extract of Hojanggeun and Gyesim.
- the dosage of the complex extract of Geunjanggeun and Gyesim is not only the administration route and the number of treatments of the pharmaceutical composition, but also the patient's age, weight, health condition, sex, disease severity, diet and excretion rate. Since the effective dose is to be determined, considering these points, those of ordinary skill in the art can use the complex extract of Giliworm root and Pyramid to prevent, treat or improve cognitive dysfunction, and/or improve learning ability or memory. It will be possible to determine an appropriate effective dosage according to the specific application for this.
- the pharmaceutical composition according to the present invention is not particularly limited in its formulation, route of administration, and method of administration as long as it exhibits the effects of the present invention.
- the pharmaceutical composition for preventing or treating cognitive dysfunction of the present invention may be used alone or in combination with surgery, radiation therapy, hormone therapy, chemotherapy, or methods using a biological response modifier.
- the pharmaceutical composition for preventing or treating cognitive dysfunction of the present invention may also be a quasi-drug composition comprising a complex extract of Hojanggeun and Gyesim.
- the complex extract of Hojanggeun and Gyesim may be added as it is or may be appropriately used in accordance with a conventional method with other quasi-drug components.
- the mixing amount of the active ingredient may be appropriately determined according to the purpose of use (prevention, health or therapeutic treatment).
- the contents of the pharmaceutical composition and health functional food composition of the present invention may be applied mutatis mutandis to the quasi-drug composition and the quasi-drug of the present invention.
- health functional food includes both the meaning of “functional food” and “health food”.
- the term "functional food” is the same term as food for special health use (FoSHU), and has a medical and medical effect processed so that the bioregulatory function is effectively displayed in addition to nutritional supply. Means high food.
- the term "health food” refers to a food having an active health maintenance or enhancing effect compared to general food
- a health supplement food refers to a food for health supplement purposes.
- functional food, health food, and health supplement food are used favorably.
- the food may be prepared in various forms such as tablets, capsules, powders, granules, liquids, pills, etc. to obtain useful effects for improving cognitive function disorders or enhancing cognitive function, learning ability, or memory.
- the health functional food composition of the present invention may also be prepared in the form of nutritional supplements, food additives, feed, etc., and target animals including humans or livestock.
- Food compositions of this type can be prepared in various forms according to conventional methods known in the art.
- General foods include, but are not limited to, beverages (including alcoholic beverages), fruits and processed foods thereof (e.g., canned fruit, canned food, jam, marmalade, etc.), fish, meat and processed foods thereof (e.g. ham, sausage) Corn beef), bread and noodles (e.g. udon, buckwheat noodles, ramen, spagate, macaroni, etc.), fruit juice, various drinks, cookies, sweets, dairy products (e.g. butter, cheese, etc.), edible vegetable oil, margarine , Vegetable protein, retort food, frozen food, various seasonings (eg, soybean paste, soy sauce, sauce, etc.), etc. can be prepared by adding a complex extract of chojanggeun and chicken heart.
- a nutritional supplement it is not limited thereto, but may be prepared by adding a complex extract of Hojanggeun and Gyesim to capsules, tablets, and pills.
- the health functional food is not limited thereto, for example, liquefied, granulated, encapsulated, and powdered so that the complex extracts of Hojanggeun and Gyesim are prepared in the form of tea, juice, and drink so that they can be consumed (healthy beverage). It can be consumed in a form.
- the complex extract of Hojanggeun and Gyesim in the form of a food additive, it may be prepared and used in the form of a powder or a concentrate.
- the complex extract of the above-mentioned hojanggeun and geunsim can be prepared in the form of a composition by mixing with known active ingredients known to be effective in preventing or improving cognitive impairment or enhancing cognitive function, learning ability, or memory. I can.
- the health drink composition may contain various flavoring agents or natural carbohydrates as an additional component, like a normal drink.
- the natural carbohydrates described above include monosaccharides such as glucose and fructose; Disaccharides such as maltose and sucrose; Polysaccharides such as dextrin and cyclodextrin; It may be a sugar alcohol such as xylitol, sorbitol, and erythritol.
- Sweeteners include natural sweeteners such as taumatin and stevia extract; Synthetic sweeteners such as saccharin and aspartame can be used.
- the ratio of the natural carbohydrate is generally about 0.01 to 0.04 g, preferably about 0.02 to 0.03 g per 100 mL of the composition of the present invention.
- the complex extract of Hojanggeun and Gyesim may be contained as an active ingredient in a food composition for preventing or improving cognitive dysfunction or a food composition for improving cognitive function, learning ability, or memory, the amount of which obtains the above preventing, improving or enhancing effect.
- an effective amount for example, it is preferably 0.01 to 100% by weight based on the total weight of the total composition, but is not particularly limited thereto.
- the food composition of the present invention is mixed with other active ingredients known to be effective in preventing or improving cognitive dysfunction or enhancing cognitive function, learning ability, or memory, together with a complex extract of Hojanggeun and Kyesim Can be manufactured.
- the health functional food of the present invention includes various nutrients, vitamins, electrolytes, flavoring agents, coloring agents, pectic acid, salts of pectic acid, alginic acid, salts of alginic acid, organic acids, protective colloid thickeners, pH adjusters, stabilizers, preservatives , Glycerin, alcohol, or a carbonating agent.
- the health food of the present invention may contain flesh for the manufacture of natural fruit juice, fruit juice beverage, or vegetable beverage. These ingredients may be used independently or in combination. The ratio of these additives is not very important, but it is generally selected from 0.01 to 0.1 parts by weight per 100 parts by weight of the composition of the present invention.
- a second aspect of the present invention relates to a method of showing a positive or beneficial effect on cognitive dysfunction, learning ability, memory and/or cognitive function by using a composition comprising the extract of jangchim root and prickly pear.
- the present invention provides a method for preventing or treating cognitive dysfunction, comprising administering to an individual in need thereof in an effective amount of a composition comprising an extract of prickly pear and ginseng.
- the present invention provides a method for improving learning ability or memory, comprising administering to an individual in need thereof in an effective amount a composition comprising a ginseng root and ginseng extract.
- the present invention provides a method for preventing or treating cognitive decline, or a method for improving cognitive function, comprising administering to an individual in need thereof in an effective amount of a composition comprising an extract of prickly pear and ginseng.
- the term “individual” includes any animal (eg, human, horse, pig, rabbit, dog, sheep, goat, non-human primate, cow, cat, guinea pig or rodent), but It is not limited thereto. These terms do not refer to a particular age or gender. Accordingly, it is intended to include adult/adult and newborn subjects, whether female/female or male/male, as well as fetuses.
- the description of the composition including the effect of the composition including the extract of Hojanggeun and Pyramid and the composition including the route of administration, the number of administrations, and the amount of administration thereof is the same as described above, and thus description thereof is omitted.
- a third aspect of the present invention relates to the use of a composition comprising a prickly pear and prickly pear extract in the manufacture of a drug and/or functional food exhibiting a positive or beneficial effect on cognitive dysfunction, learning ability, memory and/or cognitive function.
- the present invention provides a use of a composition comprising a prickly pear extract and a prickly pear extract in the manufacture of a drug and/or a functional food for preventing or treating cognitive dysfunction.
- the present invention provides a use of a composition comprising the extract of jangjanggeun and geunsim in the manufacture of a drug and / or functional food for improving learning ability or memory.
- the present invention provides a use of a composition comprising a ginseng root and prickly pear extract in the manufacture of a drug and/or a functional food for preventing or treating cognitive decline or improving cognitive function.
- composition of the present invention the description of the composition including the effect of the composition including the extracts of Hojanggeun and Pyramids and the composition including the route of administration, the number of administrations, and the amount of administration thereof is the same as described above, and thus description thereof will be omitted.
- DMEM medium and FBS were purchased from Hyclone, and gentamicin was purchased from Lonza to cultivate the microglia cell line, BV2 cells (sold in the lab of Kyung-ho Seok, Kyungpook National University).
- LPS Lipopolysaccharide
- RNA extraction For RNA extraction, MACHEREY-NAGEL's NucleoZOL was purchased, and Bio-Rad's iScript cDNA synthesis kit and iQ SYBR Green Supermix product were purchased for cDNA synthesis and real-time PCR analysis.
- brain damage caused by neuroinflammation There are several causes of inflammation in the nerve tissue, such as traumatic brain injury, infection, and autoimmune diseases, but most neuroinflammation is accompanied by activation of microglia and astrocytes. These activated cells produce inflammatory factors such as cytokines and chemokines, which promote necrosis of nerve cells.By controlling this phenomenon, brain damage caused by activated neuroinflammation can be reduced and smooth brain function can be maintained (Health Functional food functional evaluation guide, Korea Food and Drug Administration, 2019; Wang WY, Tan MS, Yu JT, Tan L.. Role of pro-inflammatory cytokines released from microglia in Alzheimer's disease. Ann Transl Med. 2015 Jun;3(10) :136).
- BV2 cells are mouse microglia cell lines that act as immune cells such as macrophages in the central nervous system.
- LPS LPS
- a bacterial-derived toxin receptors in the BV2 cell membrane react to induce inflammatory signaling.
- neuroinflammation can be realized in BV2 cells in vitro , and the method of treating the drug and verifying the effect of reducing neuroinflammation is relatively easy and widely used (Hye Yeon Nam, et. al. Ibrutinib suppresses LPS-induced neuroinflammatory responses in BV2 microglial cells and wild-type mice.J Neuroinflammation. 2018; 15: 271.Published online 2018 Sep 19).
- the effect of reducing neuroinflammation of the complex extract of Giliworm root and Gypsy core was confirmed by using BV2 cells in which the inflammatory reaction was induced, which is a microglia cell line.
- BV2 cells were cultured at 37° C. and 5% CO 2 using DMEM medium containing 5% FBS and 10 ⁇ g/ml gentamicin, and subcultured every 2 days. In order to induce an inflammatory response, 2 ⁇ 10 5 cells were placed in a 6-well plate and cultured for 24 hours before use.
- RNA was extracted according to the manufacturer's Total RNA isolation protocol. 1 ⁇ g of RNA was synthesized cDNA by reverse transcription polymerase chain reaction using iScript cDNA synthesis kit. The synthesized cDNA was analyzed by performing real-time PCR with iQ SYBR Green Supermix using the primer set of the IL-10 gene, an inflammatory cytokine in Table 2.
- the expression of the inflammatory cytokine IL-10 gene increased by LPS was decreased by a single extract of Hojanggeun root and a gypsysimus, respectively, and it was further decreased in the 1:1 complex extract, indicating that significance was shown. Confirmed. Through this, it was found that the 1:1 complex extract is more effective in inhibiting neuroinflammation than the single extract of Hojanggeun and Gyesim.
- the complex extract having a mixture weight ratio of chojanggeun: chicken core significantly increased the expression of the IL-10 gene by LPS than the 1:2 or 2:1 complex extract. It was confirmed that it suppressed and showed a significant difference. Through this, it was confirmed that the ratio of the complex extract of G. japonica root and Gyesim complex showing anti-inflammatory effect on neuroinflammation was most appropriate.
- Example 2-1 In order to confirm the effect of reducing neuroinflammation according to the mixing weight ratio through more various inflammatory factors, the expression of IL-1 ⁇ and iNOS genes was further analyzed.
- the experimental method was carried out in the same manner as in Example 2-1, and the synthesized cDNA was analyzed by real-time PCR with iQ SYBR Green Supermix using the primer set of the inflammatory cytokines IL-1 ⁇ and iNOS gene of Table 2.
- Each gene expression value including the IL-10 gene of Example 2-1 was corrected by dividing it by the gapdh expression value, which is a housekeeping gene.
- the 1:1 complex extract effectively inhibits the neuro-inflammatory response of microglia induced by LPS is sufficient evidence that the 1:1 complex extract can prevent or inhibit brain damage caused by the inflammatory response.
- the 1:1 complex extract can help maintain healthy brain function and improve brain activity.
- the ovariectomy group is divided into a simulated surgery group (Sham), an ovarian resection group (OVX)), a ⁇ -estradiol administration group (E2), and a 1:1 complex extract administration group (HG) of eosinophilia and ginseng extract.
- Sham simulated surgery group
- OVX ovarian resection group
- E2 ⁇ -estradiol administration group
- HG 1:1 complex extract administration group of eosinophilia and ginseng extract.
- Rat MCP-1 ELISA kit (DY3144-05) was purchased to measure blood MCP-1, and R&D Systems' Rat Magnetic Luminex Assay (multiplex) was used to measure TNF- ⁇ and IL-6.
- Blood dispensed in small portions in Preparation Example 2 and stored at -80°C is slowly dissolved at 4°C, and diluted to 1/4 concentration using the dilution buffer of an ELISA kit.
- the absorbance value of 450 nm is divided by the absorbance value of 540 nm, which is a correction factor, and the concentration is calculated by substituting it into the standard curve trend line calculation formula.
- the complex extract of Hojanggeun and Gyesim can be used to improve cognitive dysfunction in the menopausal model by controlling the level of MCP-1, a marker related to cognitive ability in blood.
- ICR mice of 5 weeks of age were purchased from Coretech, Inc., and the feed was purchased from Purina's rat feed.
- Donepezil, ascorbic acid and scopolamine were purchased from Sigma, and PBS (Phosphate buffered saline) was purchased from Hyclone.
- ICR mice were reared to have free access to feed and water under constant temperature (23 ⁇ 1°C) and humidity (50 ⁇ 5%) after wearing. After adapting to the breeding environment for 1 week and measuring the weight, it was divided into six groups as shown in Table 3. After the adaptation period, donepezil 5 mg/kg in the positive control group, and 1:1 complex extracts of Hojanggeun and Kyesim in the experimental groups 1, 2 and 3 at concentrations of 50 mg/kg, 100 mg/kg, and 200 mg/kg, respectively, The same amount of distilled water was orally administered to the control group 1 and the control group 2 in the same manner. Administration was performed once a day for a total of 8 weeks.
- Control 1 (vehicle) Control 2 (scopolamine) Positive control group (Donepezil) Experimental group 1 (HG 50mg/kg) Experimental group 2 (HG 100mg/kg) Experimental group 3 (HG 200mg/kg) Oral administration Distilled water (DW) Distilled water (DW) Donepezil 5mg/kg Complex extract 50mg/kg Complex extract 100mg/kg Complex extract 200mg/kg i.p. injection PBS Scopolamine 1mg/kg Mari number 10 10 10 10 10 10 10 10 10 10 10 10 10 10 10 10
- the mouse model for inducing dementia by anticholinergic drugs such as Scopolamine is a model that is widely used because of its short dementia induction period and easy experimental method (Preston GC et al., (1988).
- the scopolamine model of dementia determination of central cholinomimetic effects of physostigmine on cognition and biochemical markers in man.J Psychopharmacol. 2(2), 67-79; Jinghua Wang et al. (2014). Effects of Fructus Akebiae on learning and memory impairment in a scopolamine -induced animal model of dementia. 8(2), 671-675).
- scopolamine at a concentration of 1 mg/kg 30 minutes before the behavioral test for measuring learning and memory ability was injected by intraperitoneal injection (i.p. injection) to induce dementia in experimental animals.
- Control 1 was injected with the same amount of phosphate buffered saline (PBS) as a vehicle.
- PBS phosphate buffered saline
- japonica and gypsysimus entered the arm of the Y-type maze at the same number of times as the control group 2. It can be seen that the complex extracts of long roots and ginsengs have increased spatial awareness and short-term memory ability by recovering dementia induced by scopolamine.
- the passive avoidance test apparatus consists of two zones, a light chamber and a dark chamber, and the floor is made of wire mesh.
- the mice On the first day (Training day), the mice were placed in a bright chamber and allowed to acclimate for 20 seconds, and then the door to the dark chamber was opened. When the mouse completely entered the dark chamber, the door was closed and an electric shock of 0.3 mA was applied for 3 seconds. The time to enter the dark chamber was recorded and the mice returned to the cage. 24 hours later, the next day (Aquisition day), the test substances were administered orally 1 hour before the behavioral experiment, and scopolamine was injected intraperitoneally after 30 minutes. After 30 minutes, the mice were placed in a bright chamber in the same manner as on the first day, and the time until entering the dark chamber was recorded. The maximum measurement time was set to 300 seconds.
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Abstract
La présente invention concerne l'utilisation d'une composition pour la prévention, l'amélioration ou le traitement d'un dysfonctionnement cognitif comprenant un extrait de racine de Polygonum cuspidata et de Cinnamomum cassia.
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Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR20080088163A (ko) * | 2007-03-29 | 2008-10-02 | 경희대학교 산학협력단 | 호장근 분획물을 함유하는 신경 보호용 약학적 조성물 |
KR20080088162A (ko) * | 2007-03-29 | 2008-10-02 | 경희대학교 산학협력단 | 호장근 추출물을 함유하는 신경 보호용 약학적 조성물 |
KR20150111073A (ko) * | 2014-03-25 | 2015-10-05 | 단국대학교 천안캠퍼스 산학협력단 | 육계 추출물을 유효성분으로 포함하는 퇴행성 뇌 질환 예방 또는 치료용약학적 조성물 |
KR20160002068A (ko) * | 2014-06-30 | 2016-01-07 | 연세대학교 원주산학협력단 | 육계 냉수 추출물을 유효성분으로 함유하는 신생혈관형성 억제 활성을 갖는 약학적 조성물 |
KR20190047359A (ko) * | 2017-10-27 | 2019-05-08 | 주식회사 노브메타파마 | 호장근과 계심을 함유하는 항혈전용 조성물 |
-
2020
- 2020-07-30 KR KR1020200095466A patent/KR102406795B1/ko active IP Right Grant
- 2020-07-30 WO PCT/KR2020/010080 patent/WO2021020912A1/fr active Application Filing
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR20080088163A (ko) * | 2007-03-29 | 2008-10-02 | 경희대학교 산학협력단 | 호장근 분획물을 함유하는 신경 보호용 약학적 조성물 |
KR20080088162A (ko) * | 2007-03-29 | 2008-10-02 | 경희대학교 산학협력단 | 호장근 추출물을 함유하는 신경 보호용 약학적 조성물 |
KR20150111073A (ko) * | 2014-03-25 | 2015-10-05 | 단국대학교 천안캠퍼스 산학협력단 | 육계 추출물을 유효성분으로 포함하는 퇴행성 뇌 질환 예방 또는 치료용약학적 조성물 |
KR20160002068A (ko) * | 2014-06-30 | 2016-01-07 | 연세대학교 원주산학협력단 | 육계 냉수 추출물을 유효성분으로 함유하는 신생혈관형성 억제 활성을 갖는 약학적 조성물 |
KR20190047359A (ko) * | 2017-10-27 | 2019-05-08 | 주식회사 노브메타파마 | 호장근과 계심을 함유하는 항혈전용 조성물 |
Non-Patent Citations (1)
Title |
---|
CHENG Y; ZHANG H T; SUN L; GUO S; OUYANG S; ZHANG Y; XU J: "Involvement of cell adhesion molecules in polydatin protection of brain tissues from ischemia-reperfusion injury", BRAIN RESEARCH, vol. 1110, no. 1, 19 September 2006 (2006-09-19), pages 193 - 200, XP027955052, ISSN: 0006-8993, DOI: 10.1016/j.brainres.2006.06.068 * |
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