WO2021225343A1 - Composition comprenant un extrait d'iris lactea, destinée à prévenir ou traiter un trouble cognitif - Google Patents

Composition comprenant un extrait d'iris lactea, destinée à prévenir ou traiter un trouble cognitif Download PDF

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WO2021225343A1
WO2021225343A1 PCT/KR2021/005560 KR2021005560W WO2021225343A1 WO 2021225343 A1 WO2021225343 A1 WO 2021225343A1 KR 2021005560 W KR2021005560 W KR 2021005560W WO 2021225343 A1 WO2021225343 A1 WO 2021225343A1
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extract
iris
cognitive impairment
pharmaceutical composition
composition
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PCT/KR2021/005560
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English (en)
Korean (ko)
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전원경
김민수
방지혜
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한국한의학연구원
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Priority claimed from KR1020210055206A external-priority patent/KR102634302B1/ko
Application filed by 한국한의학연구원 filed Critical 한국한의학연구원
Publication of WO2021225343A1 publication Critical patent/WO2021225343A1/fr

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    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K10/00—Animal feeding-stuffs
    • A23K10/30—Animal feeding-stuffs from material of plant origin, e.g. roots, seeds or hay; from material of fungal origin, e.g. mushrooms
    • 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
    • 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)
    • A61K36/88—Liliopsida (monocotyledons)
    • 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

Definitions

  • the present invention relates to a composition for the prevention or treatment of cognitive impairment comprising an iris extract (Iris Lactea Extract, ILE) or a fraction thereof, and specifically, the prevention, improvement or treatment of cognitive impairment comprising an iris extract or a fraction thereof as an active ingredient therapeutic pharmaceutical compositions; food composition; It relates to a feed composition and a method for treating cognitive impairment using the pharmaceutical composition.
  • an iris extract Iris Lactea Extract, ILE
  • a fraction thereof specifically, the prevention, improvement or treatment of cognitive impairment comprising an iris extract or a fraction thereof as an active ingredient therapeutic pharmaceutical compositions
  • food composition It relates to a feed composition and a method for treating cognitive impairment using the pharmaceutical composition.
  • Cognitive ability encompasses memory ability, space-time grasping ability, judgment ability, language ability, and calculation ability, and enables one to perform daily life without the help of others.
  • brain damage such as rapid neuronal cell death induced by stroke, trauma, or the like, or slow neuronal cell death that causes degenerative brain disease, it immediately causes irreversible dysfunction of the neural network.
  • cognitive ability is lowered, and people suffer from diseases such as forgetfulness or memory impairment, dementia, Alzheimer's disease, and the like, and they are unable to maintain their previous level of daily life.
  • Publication No. 2014-0144785 relates to a composition for enhancing memory and learning ability comprising a citron extract as an active ingredient
  • Registration No. 10-1837444 relates to a composition for the prevention, improvement or treatment of cognitive dysfunction containing a hollyhock flower extract as an active ingredient
  • Registration No. 10-1823892 relates to an extract of Balsam balsam, which improves memory, improves cognitive ability, prevents, delays, or treats dementia.
  • an excellent formulation with a certain efficacy has not yet been developed.
  • commercially available drugs cause many side effects such as hepatotoxicity, insomnia, hypertension, and vomiting. Therefore, there is an urgent need to develop a formulation capable of effectively treating cognitive impairment while having few side effects.
  • the present inventors have studied diligently to develop a substance that can treat cognitive disorders such as vascular dementia and memory impairment (memory impairment).
  • cognitive disorders such as vascular dementia and memory impairment (memory impairment).
  • the iris lactea extract has excellent therapeutic effect on cognitive impairment caused by brain damage.
  • the present invention was completed.
  • One object of the present invention is to provide a pharmaceutical composition for preventing or treating cognitive impairment comprising Iris Lactea Extract (ILE) or a fraction thereof as an active ingredient.
  • ILE Iris Lactea Extract
  • Another object of the present invention is to provide a method for preventing or treating cognitive impairment comprising administering the pharmaceutical composition to an individual.
  • Another object of the present invention is to provide a food composition for preventing or improving cognitive impairment comprising an iris extract or a fraction thereof as an active ingredient.
  • Another object of the present invention is to provide a feed composition for preventing or improving cognitive impairment comprising an iris extract or a fraction thereof as an active ingredient.
  • Iris Lactea Extract of the present invention exhibits an excellent normalizing effect and memory enhancement effect on brain damage such as basal forebrain, white matter, hippocampus, etc. It can be usefully used in the treatment of cognitive disorders related to the back.
  • FIG. 1 is a diagram showing an experimental design for measuring the effect of an iris extract (Iris Lactea Extract) on object and location cognitive memory.
  • FIG. 2 is a diagram showing the intrinsic object detection behavior of the mouse, and the Y-axis represents the total time (object exploration time) for the mouse to approach the object and explore the object during the training period.
  • Sham + VEH saline, saline
  • UCCAO+VEH saline, saline
  • UCCAO+ILE100 was the experimental group in which 100 mg/kg of iris extract was administered to the brain injured group
  • UCCAO+ILE200 was the experimental group in which 200 mg/kg of iris extract was administered to the brain injured group
  • UCCAO+ILE400 refers to the experimental group in which 400 mg/kg of iris extract was administered to the brain damage group, and the description of the above categories is equally applied to the drawings below.
  • the Y-axis represents a scale (recognition index) that quantifies and compares the search time for a new object compared to an existing object or a new location compared to an existing location.
  • FIG. 4 is a diagram showing the normalization effect of memory-related factors (PI3K-Akt-CREB-BDNF pathway) of iris extract in the hippocampus, and shows the phosphorylation of PI3K, Akt, and CREB proteins and Western blot results for BDNF proteins.
  • PI3K-Akt-CREB-BDNF pathway memory-related factors
  • FIG. 5 is a graph obtained by quantifying western blot bands for phospho-PI3K, phospho-Akt, phospho-CREB and BDNF proteins according to FIG. 4 .
  • FIG. 6 is a view showing the normalization effect of tau-related factors (PI3K-Akt-GSK3 ⁇ -tau) of iris extract in the hippocampus, and shows the results of western blot for phosphorylation of GSK3 ⁇ and tau protein.
  • tau-related factors PI3K-Akt-GSK3 ⁇ -tau
  • FIG. 7 is a graph obtained by quantifying and quantifying Western blot bands for phospho-GSK3 ⁇ (ser9), phospho-Tau (Thr212) and phospho-Tau (Ser199/202) proteins according to FIG. 6 .
  • FIG. 8 is a view showing the demyelination normalization effect of myelin in the corpus callosum tissue in the white matter of the iris extract, and shows the results of immunofluorescence staining for the MBP protein.
  • FIG. 9 is a graph obtained by quantifying and quantifying the results of immunofluorescence staining for the MBP protein according to FIG. 8 .
  • FIG. 10 is a diagram showing the inhibitory effect of iris extract on gliosis in hippocampus tissue, and shows the results of immunofluorescence staining for Iba-1 protein.
  • FIG. 11 is a graph obtained by quantifying the results of immunofluorescence staining for the Iba-1 protein according to FIG. 10 .
  • FIG. 12 is a view showing the normalization effect of cholinergic neurons in the basal forebrain (Substantia innominata-nucleus basalis magnocellularis) tissue of the iris extract, and shows the results of immunohistochemical staining for ChAT protein.
  • FIG. 13 is a graph quantifying and quantifying the results of immunohistochemical staining for the ChAT protein according to FIG. 12 .
  • the present invention provides a pharmaceutical composition for preventing or treating cognitive impairment comprising Iris Lactea Extract (ILE) or a fraction thereof as an active ingredient.
  • ILE Iris Lactea Extract
  • the present invention provides a use of the extract or a fraction thereof for the prevention or treatment of cognitive impairment.
  • iris is a perennial plant of the Iridaceae family, native to temperate and subtropical Asian regions inhabiting various temperate regions at an altitude of 600 to 380 m above sea level. Flowers range in color from pale blue to purple, white or yellow. In oriental medicine, it is used as a contraceptive for fever, jaundice, sore throat, and vomiting blisters, and the leaves are used as animal feed.
  • the iris may be purchased and used commercially, or collected or grown in nature, but is not limited thereto.
  • extract refers to a liquid component obtained by immersing a target substance in various solvents and then extracting it for a certain time at room temperature or in a heated state, and a solid obtained by removing the solvent from the liquid component. it means.
  • it can be comprehensively interpreted as including all of the diluent of the result, the concentrate thereof, the prepared product thereof, the purified product, and the like.
  • the iris extract (Iris lacteal extract; ILE) provided in the present invention is an extract obtained by extracting it, a diluted or concentrated liquid of the extract, a dried product obtained by drying the extract, a prepared or purified product of the extract, or It can be interpreted to include extracts of all formulations that can be formed using the extract itself and the extract, such as mixtures thereof.
  • the extraction method thereof is not particularly limited, and may be extracted according to a method commonly used in the art.
  • Non-limiting examples of the extraction method include hot water extraction, ultrasonic extraction, filtration, reflux extraction, and the like, and these may be performed alone or in combination of two or more methods.
  • the kind of solvent used for the extraction is not particularly limited, and any solvent known in the art may be used.
  • Non-limiting examples of the extraction solvent include water, alcohol, or a mixed solvent thereof, and these may be used alone or in combination of one or more, and specifically alcohol may be used, mainly having 1 to 4 carbon atoms. of alcohol can be used.
  • the extract may be prepared and used in the form of a dry powder after extraction, but is not limited thereto.
  • the extract may be a seed extract of iris.
  • the term "cognitive disorder” refers to a state caused by a decrease in cognitive function, a disease resulting from it, and any disease that has it as a symptom. decline and other declines in mental function may be included.
  • the cognitive impairment may specifically refer to vascular cognitive impairment.
  • the vascular cognitive impairment refers to all cognitive dysfunctions caused by cerebrovascular diseases, and may be one or more selected from the group consisting of vascular dementia, as well as vascular mild cognitive impairment, stroke, cerebral infarction, cerebral hemorrhage or cerebral hemorrhage. .
  • the vascular dementia includes multi-infarct dementia, strategic infarct dementia, subcortical vascular dementia, hypoperfusion dementia, and hemorrhagic dementia. , hereditary vascular dementia, or mixed dementia of Alzheimer's disease and vascular dementia.
  • prevention refers to any action that inhibits or delays the onset of cognitive impairment by administration of the pharmaceutical composition according to the present invention.
  • treatment refers to any action in which the symptoms of the suspected and affected individuals of cognitive impairment are improved or beneficially changed by administration of the pharmaceutical composition.
  • the pharmaceutical composition of the present invention may include the extract in an amount of 0.001 to 80, specifically 0.001 to 70, more specifically 0.001 to 60% by weight based on the total weight of the composition, but is not limited thereto.
  • the pharmaceutical composition may further include a pharmaceutically acceptable carrier, excipient or diluent commonly used in the preparation of the pharmaceutical composition, and the carrier may include a non-naturally occurring carrier.
  • the carrier, excipient and diluent include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum acacia, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil.
  • the pharmaceutical composition is prepared according to a conventional method for each tablet, pill, powder, granule, capsule, suspension, internal solution, emulsion, syrup, sterilized aqueous solution, non-aqueous solution, suspension, emulsion, freeze-dried formulation, transdermal It can be formulated and used in the form of absorbents, gels, lotions, ointments, creams, patches, cataplasmas, pastes, sprays, skin emulsions, skin suspensions, transdermally delivered patches, drug-containing bandages or suppositories.
  • a diluent or excipient such as a filler, a weight agent, a binder, a wetting agent, a disintegrant, a surfactant, etc. commonly used.
  • Solid preparations for oral administration include, but are not limited to, tablets, pills, powders, granules, capsules, and the like.
  • Such a solid preparation may be prepared by mixing at least one or more excipients, for example, starch, calcium carbonate, sucrose, lactose, gelatin, and the like.
  • lubricants such as magnesium stearate and talc may also be used.
  • Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, lyophilized formulations and suppositories.
  • non-aqueous solvent and suspending agent propylene glycol, polyethylene glycol, vegetable oils such as olive oil, injectable esters such as ethyl oleate, and the like can be used.
  • base of the suppository Witepsol, Macrogol, Tween 61, cacao butter, laurin, glycerogelatin, etc. may be used.
  • the treatment of cognitive impairment in the present invention may be one obtained by improving memory ability, normalizing memory-related factors, inhibiting tau hyperphosphorylation, normalizing white matter damage, inhibiting glial activity, and normalizing cholinergic neurons through a dementia-simulating animal model.
  • an effect of improving cognitive ability due to brain damage of the extract was confirmed through an experiment in which a dementia mimic animal model was manufactured and a seed extract of iris lactea was administered to the model (Fig. 3).
  • the seed extract of iris lactea of the present invention increases and normalizes the memory-related factors of the hippocampus reduced by brain damage ( FIGS. 4 and 5 )
  • the seed extract of iris lactea of the present invention normalizes the expression of tau-related factors in the hippocampus hyperphosphorylated by brain damage ( FIGS. 6 and 7 ).
  • the seed extract of iris lactea of the present invention effectively inhibits myelin myelin caused by brain damage to normalize white matter damage ( FIGS. 8 and 9 ).
  • the seed extract of iris lactea of the present invention effectively inhibits glial cells activated by brain damage to normalize hippocampal damage ( FIGS. 10 and 11 ).
  • the seed extract of iris lactea of the present invention increases the number of cholinergic neurons reduced by brain damage to normalize cholinergic neurons in the basal forebrain ( FIGS. 12 and 13 ) .
  • the seed extract of iris lactea provided in the present invention can be effectively used for the prevention or treatment of cognitive impairment.
  • Another aspect of the present invention for achieving the above object provides a method for treating cognitive impairment comprising administering the pharmaceutical composition to an individual suspected of having a cognitive impairment.
  • the term “administration” refers to the act of introducing a composition comprising the extract to an individual by an appropriate method.
  • the term "individual” refers to all animals, including humans, rats, mice, and livestock that have or may develop cognitive impairment. As a specific example, it may be a mammal including a human.
  • the pharmaceutical composition of the present invention is administered in a pharmaceutically effective amount.
  • pharmaceutically effective amount means an amount sufficient to treat a disease with a reasonable benefit/risk ratio applicable to medical treatment, and the effective dose level is determined by the type and severity of the subject, age, sex, activity of the drug, Sensitivity to the drug, time of administration, route of administration and rate of excretion, duration of treatment, factors including concomitant drugs, and other factors well known in the medical field.
  • the iris extract may be administered at a dose of 0.01 to 5000 mg/kg per day, specifically, at a dose of 10 to 1000 mg/kg, and the administration may be administered once a day or divided several times.
  • the pharmaceutical composition may be administered as an individual therapeutic agent or may be administered in combination with other therapeutic agents, and may be administered sequentially or simultaneously with conventional therapeutic agents. and may be administered single or multiple. Taking all of the above factors into consideration, it is important to administer an amount that can obtain the maximum effect with a minimum amount without side effects, and can be easily determined by those skilled in the art.
  • the pharmaceutical composition may be administered orally or parenterally (eg, intravenously, subcutaneously, intraperitoneally or topically) according to a desired method, and the dosage may vary depending on the patient's condition and weight, and the degree of disease. , depending on the drug form, administration route and time, but may be appropriately selected by those skilled in the art.
  • Another aspect of the present invention for achieving the above object provides a food composition for preventing or improving cognitive impairment comprising an iris extract or a fraction thereof.
  • the term “improvement” refers to any action that at least reduces a parameter related to a condition to be treated, for example, the severity of a symptom by administration of a composition comprising the extract.
  • the term "food” refers to meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gums, dairy products including ice cream, various soups, beverages, tea, drinks, alcoholic beverages , vitamin complexes, health functional foods, and health foods, and includes all foods in a conventional sense.
  • the food composition of the present invention is derived from serrano goreng that can be consumed on a daily basis, a high lung cancer improvement effect can be expected, and thus it can be very usefully used for health promotion purposes.
  • the functional food is the same term as food for special health use (FoSHU), and in addition to supplying nutrients, it is processed to efficiently exhibit bioregulatory functions and has high medical effects.
  • 'function (sex)' refers to obtaining useful effects for health purposes, such as regulating nutrients or physiological effects on the structure and function of the human body.
  • the food of the present invention can be prepared by a method commonly used in the art, and at the time of manufacture, it can be prepared by adding raw materials and components commonly added in the art.
  • the formulation of the food can be prepared without limitation as long as it is a formulation recognized as a food.
  • composition for food of the present invention can be prepared in various forms, and unlike general drugs, it has the advantage that there are no side effects that may occur when taking the drug for a long period of time by using a natural product as a raw material, and it is excellent in portability.
  • the food of the invention can be ingested as an adjuvant to enhance the effect of improving cognitive impairment.
  • the health food means a food having an active health maintenance or promotion effect compared to general food
  • the health supplement food means a food for the purpose of health supplementation.
  • the terms health functional food, health food, and dietary supplement are preferred.
  • the health functional food is a food prepared by adding the composition of the present invention to food materials such as beverages, teas, spices, gum, and confectionery, or encapsulating, powdering, suspension, etc., and when ingested, It means to bring an effect, but unlike general drugs, it has the advantage that there are no side effects that may occur when taking the drug for a long time using food as a raw material.
  • the food composition may further include a physiologically acceptable carrier, the type of carrier is not particularly limited and any carrier commonly used in the art may be used.
  • the food composition may include additional ingredients that are commonly used in food compositions to improve odor, taste, vision, and the like.
  • vitamins A, C, D, E, B1, B2, B6, B12, niacin, biotin, folate, pantothenic acid, and the like may be included.
  • minerals such as zinc (Zn), iron (Fe), calcium (Ca), chromium (Cr), magnesium (Mg), manganese (Mn), copper (Cu), chromium (Cr); and amino acids such as lysine, tryptophan, cysteine, and valine.
  • the food composition includes a preservative (potassium sorbate, sodium benzoate, salicylic acid, sodium dehydroacetate, etc.), a disinfectant (bleaching powder and high bleaching powder, sodium hypochlorite, etc.), an antioxidant (butylhydroxyanisole (BHA), butyl hydro Loxytoluene (BHT), etc.), coloring agents (tar pigments, etc.), coloring agents (sodium nitrite, sodium nitrite, etc.), bleach (sodium sulfite), seasonings (MSG sodium glutamate, etc.), sweeteners (dulcin, cyclamate, saccharin, etc.) , sodium, etc.), flavorings (vanillin, lactones, etc.), swelling agents (alum, potassium hydrogen tartrate, etc.), strengthening agents, emulsifiers, thickeners (flavors), film agents, gum base agents, foam inhibitors, solvents, improvers, etc. It may contain food additives.
  • the additive may be
  • the food composition of the present invention may be used as a health drink composition, and in this case, it may contain various flavoring agents or natural carbohydrates as an additional component like a conventional drink.
  • the above-mentioned natural carbohydrates 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, or erythritol.
  • Sweeteners include natural sweeteners such as taumatin, stevia extract; A synthetic sweetener such as saccharin or aspartame may be used.
  • the ratio of the natural carbohydrate may be generally about 0.01 to 0.04 g, specifically about 0.02 to 0.03 g per 100 ml of the health beverage composition of the present invention.
  • the health beverage composition includes various nutrients, vitamins, electrolytes, flavoring agents, colorants, pectic acid, pectic acid salts, alginic acid, alginic acid salts, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, It may contain alcohol, a carbonation agent, and the like. In addition, it may contain the pulp for the production of natural fruit juice, fruit juice beverage, or vegetable beverage. These components may be used independently or in combination.
  • the ratio of these additives is not very important, it is generally selected in the range of 0.01 to 0.1 parts by weight per 100 parts by weight of the health beverage composition of the present invention.
  • Another aspect of the present invention for achieving the above object provides a feed composition for preventing or improving cognitive impairment comprising an iris extract or a fraction thereof.
  • the iris extract according to the present invention exhibits an excellent therapeutic effect on cognitive impairment, it may be included in a feed composition for the purpose of preventing or improving vascular cognitive function, and since the feed composition can be routinely ingested by animals, vascular cognition A high effect can be expected for the prevention or improvement of function.
  • feed means any natural or artificial diet, meal, etc., or a component of said meal, intended for or suitable for eating, ingestion, and digestion by an animal.
  • the type of feed is not particularly limited, and feed commonly used in the art may be used.
  • Non-limiting examples of the feed include plant feeds such as grains, root fruits, food processing by-products, algae, fibers, pharmaceutical by-products, oils and fats, starches, gourds or grain by-products; and animal feeds such as proteins, inorganic materials, oils and fats, mineral oils, oils and fats, single cell proteins, zooplankton, or food. These may be used alone or in mixture of two or more.
  • Example 1 Establishment of a method for oral administration of drugs and construction of an animal model that simulates dementia
  • Example 1-1 Method of making a dementia-simulating animal model
  • a dementia-simulating animal model was first prepared.
  • mice 8-week-old C57BL/6 mice were supplied from Orient Co., Ltd. (Jungwon-gu, Seongnam-si, Gyeonggi-do) and used. The animals were acclimatized for 7 days, and the temperature of the animal room was 23 ⁇ 3°C, 50 ⁇ 10% relative humidity, 12 hours light/dark cycle (light on 7:00, turn off 19:00), and illuminance of 150 ⁇ 300 Lx. Adjusted to maintain constant breeding environment conditions. In addition, water and solid feed (PMI nutrition, USA) were allowed to be freely ingested for 24 hours.
  • the carotid artery was ligated using a nylon thread to induce interruption of blood supply, thereby preparing an experimental animal for inducing brain damage. After that, the incision site was closed with a suture and observed for 20 minutes to recover from anesthesia.
  • Example 1-2 Method of oral administration of iris extract
  • Example 1-1 After the operation of Example 1-1, the iris extract was diluted with physiological saline (Saline) and administered orally for 60 days from 14 days elapsed. It was divided into a total of 5 groups listed in [Table 1] below, and the same volume of physiological saline (Saline) was orally administered to the control group. Oral administration was set to a total of three concentrations, low (100 mg/kg), medium (200 mg/kg), and high (400 mg/kg) concentrations.
  • a white box 40 x 40 x 40 cm
  • the mouse was allowed to explore freely for 10 minutes to adapt to the box (Box habituation).
  • the mice were allowed to adapt to the two objects for 10 minutes (Training).
  • the mouse was also allowed to access both objects for 5 minutes (Novel location test).
  • Object and location recognition ability was compared by numerically quantifying the search degree (time) for a new object compared to an existing object or a new location compared to an existing location.
  • the iris extract administration group showed higher recognition ability for new objects and locations than the negative control group administered with physiological saline. It was confirmed that new objects and positions were recognized. Through these results, it was found that the iris extract has an effect of improving cognitive ability due to brain damage in mice, and thus can be usefully used for the prevention and treatment of cognitive disorders such as memory impairment and dementia.
  • the expression of memory-related factors in the hippocampus was measured after administration of the iris extract according to the method of Example 1.
  • PI3K Phosphoinositide 3-kinase
  • Akt Protein kinase B
  • phospho-Akt Protein kinase B
  • phospho-Akt Akt
  • CREB Phosphoinositide 3-kinase
  • phospho-PI3K The expression levels of cAMP-response element binding protein), phospho-CREB and BDNF (Brain-derived neurotrophic factor) proteins were analyzed.
  • ⁇ -Actin was used as a loading control.
  • the expression levels of phospho-PI3K, phospho-Akt, phospho-CREB and BDNF proteins were significantly increased in the iris extract-administered group compared to the negative control group.
  • the 200 and 400 mg/kg iris extract group recovered to a similar extent to that of the normal control group.
  • the iris extract increases and normalizes the memory-related factors of the hippocampus reduced by brain damage in mice, so that it can be usefully used for the prevention and treatment of cognitive disorders such as memory disorders and dementia.
  • Tau hyperphosphorylation is a substance that induces entanglement of filamentous nerve fibers within the brain neurons (neurons) of patients with cognitive impairment, and is known as a key phenomenon inducing cognitive impairment.
  • mice hippocampus of mice was harvested and then GSK3 ⁇ (Glycogen synthase kinase 3 beta), phospho-ser9-GSK3 ⁇ , Tau, phospho-Thr212-tau and phospho- The expression level of Ser199/202-tau protein was analyzed.
  • the degree of myelin demyelination in the corpus callosum was analyzed after administration of the iris extract according to the method of Example 1. Since myelin myelin mediates signal transmission between nerve cells, so-called demyelination, in which myelin myelin is peeled off, cuts off this signal transmission and increases the risk of cognitive impairment.
  • mice after administration of the iris extract and the cognition test were perfused, fixed with 4% paraformaldehyde, and then the brain tissue was cut into 40 ⁇ m increments and immunofluorescent staining was performed. After reacting the sections with normal goat serum, they were stained with MBP (Myelin basic protein, 1:1000) as the primary antibody and goat anti-mouse (1:200) as the secondary antibody. In order to stain the brain structure (counterstain), it was reacted with DAPI (4',6-diamidino-2-phenylindole, 1:2500) for 10 minutes.
  • MBP Myelin basic protein, 1:1000
  • DAPI 4,6-diamidino-2-phenylindole, 1:2500
  • the iris extract administered group significantly increased the density of MBP protein in the corpus callosum compared to the negative control group, indicating that the iris extract effectively inhibited myelin demyelination. .
  • the 200 and 400 mg/kg iris extract groups showed similar effects to the normal control group.
  • microglia act as phagocytes for wastes in the nervous tissue, and play a role in removing degenerated neurons or foreign substances from within the tissue. Thus, the increase in microglia indicates that brain damage was caused.
  • mice after administration of the iris extract and the cognition test were perfused, fixed with 4% paraformaldehyde, and then the brain tissue was cut into 40 ⁇ m increments and immunofluorescent staining was performed. After reacting the sections with normal goat serum, they were stained with Iba-1 (ionized calcium-binding adapter molecule, 1:1000) as a primary antibody and donkey anti-rabbit (1:200) as a secondary antibody. In order to stain the brain structure (counterstain), it was reacted with DAPI (4',6-diamidino-2-phenylindole, 1:2500) for 10 minutes.
  • Iba-1 ionized calcium-binding adapter molecule
  • the iris extract administration group significantly reduced the density of Iba-1 protein in the hippocampus compared to the negative control group, indicating that the iris extract effectively inhibited microglia. .
  • the 200 and 400 mg/kg iris extract administration groups showed similar effects to the normal control group.
  • the number of cholinergic neurons in the basal forebrain was analyzed after administration of the iris extract according to the method of Example 1. Cholinergic neurons play a key role in learning and memory by secreting neurotransmitters, and it is known that cholinergic neurons degenerate in patients with brain damage such as dementia.
  • mice were perfused, fixed with 4% paraformaldehyde, and brain tissue was cut into 40 ⁇ m increments to perform immunohistochemical staining. After reacting the sections with normal horse serum, they were stained with ChAT (Choline acetyltransferase, 1:1000) as the primary antibody and rabbit anti-goat (1:500) as the secondary antibody.
  • ChAT Choline acetyltransferase, 1:1000
  • rabbit anti-goat (1:500
  • iris extract normalizes cholinergic neurons in the basal forebrain by increasing the number of cholinergic neurons reduced by brain damage in mice, so it can be usefully used for the prevention and treatment of cognitive disorders such as memory disorders and dementia. And it was found.

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Abstract

La présente invention concerne une composition comprenant un extrait d'Iris lactea ou une fraction de celui-ci, destinée à prévenir ou traiter un trouble cognitif. L'invention concerne en particulier : une composition pharmaceutique comprenant un extrait d'Iris lactea ou une fraction de celui-ci comme principe actif, destinée à prévenir ou traiter un trouble cognitif ; une composition alimentaire ; une composition alimentaire animale ; ainsi qu'une méthode de traitement d'un trouble cognitif au moyen de cette composition pharmaceutique. L'extrait d'Iris lactea selon l'invention présente d'excellents effets de normalisation et d'amélioration de la mémoire dans un contexte de lésions cérébrales, notamment au cerveau antérieur basal, à la substance blanche et à l'hippocampe, et peut par conséquent être utilisé efficacement dans le traitement d'un trouble cognitif lié à des troubles de la mémoire et des troubles cérébrovasculaires induits par les lésions, tels que la démence vasculaire et l'infarctus cérébral.
PCT/KR2021/005560 2020-05-06 2021-05-03 Composition comprenant un extrait d'iris lactea, destinée à prévenir ou traiter un trouble cognitif WO2021225343A1 (fr)

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KR20200054104 2020-05-06
KR10-2020-0054104 2020-05-06
KR10-2021-0055206 2021-04-28
KR1020210055206A KR102634302B1 (ko) 2020-05-06 2021-04-28 붓꽃 추출물을 포함하는 인지장애의 예방 또는 치료용 조성물

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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009121155A2 (fr) * 2008-04-01 2009-10-08 Aché Laboratórios Farmacêuticos S/A Utilisation d'une ou de plusieurs benzopyranones, composition pharmaceutique et procédé de prévention ou de traitement de maladies, de dysfonctionnements et de perturbations associés à la monoamone oxydase
KR20150019505A (ko) * 2013-08-14 2015-02-25 대화제약 주식회사 플라본-6-c-글루코스 유도체를 유효성분으로 함유하는 신경정신질환의 치료 또는 예방용 약학적 조성물
KR20190075053A (ko) * 2016-10-28 2019-06-28 제리아 신야쿠 고교 가부시키 가이샤 인지기능 저하 억제제

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009121155A2 (fr) * 2008-04-01 2009-10-08 Aché Laboratórios Farmacêuticos S/A Utilisation d'une ou de plusieurs benzopyranones, composition pharmaceutique et procédé de prévention ou de traitement de maladies, de dysfonctionnements et de perturbations associés à la monoamone oxydase
KR20150019505A (ko) * 2013-08-14 2015-02-25 대화제약 주식회사 플라본-6-c-글루코스 유도체를 유효성분으로 함유하는 신경정신질환의 치료 또는 예방용 약학적 조성물
KR20190075053A (ko) * 2016-10-28 2019-06-28 제리아 신야쿠 고교 가부시키 가이샤 인지기능 저하 억제제

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
BORHANI MONA, SHARIFZADEH MOHAMMAD, FARZAEI MOHAMMAD HOSEIN, NARIMANI ZAHRA, SABBAGHZIARANI FATEMEH, GHOLAMI MAHDI, RAHIMI ROJA: "PROTECTIVE EFFECT OF IRIS GERMANICA L. IN Β-AMYLOID-INDUCED ANIMAL MODEL OF ALZHEIMER’S DISEASE", AFRICAN JOURNAL OF TRADITIONAL, COMPLEMENTARY AND ALTERNATIVEMEDICINES, AFRICAN ETHNOMEDICINES NETWORK,, NG, vol. 14, no. 4, 5 July 2017 (2017-07-05), NG , pages 140 - 148, XP055863733, ISSN: 0189-6016, DOI: 10.21010/ajtcam.v14i4.17 *
MURRAY ANA PAULA, FARAONI MARÍA BELÉN, MARÍA JULIA, CASTRO, ALZA NATALIA PAOLA, CAVALLARO VALERIA: "Natural AChE Inhibitors from Plants and their Contribution to Alzheimer's Disease Therapy", CURRENT NEUROPHARMACOLOGY., 1 January 2013 (2013-01-01), pages 388 - 413, XP055863735, Retrieved from the Internet <URL:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3744903/pdf/CN-11-388.pdf> [retrieved on 20211119] *

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