WO2017048051A1 - Composition pharmaceutique destinée à prévenir ou à traiter les troubles de la fonction cognitive ou les maladies dégénératives du cerveau - Google Patents

Composition pharmaceutique destinée à prévenir ou à traiter les troubles de la fonction cognitive ou les maladies dégénératives du cerveau Download PDF

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WO2017048051A1
WO2017048051A1 PCT/KR2016/010336 KR2016010336W WO2017048051A1 WO 2017048051 A1 WO2017048051 A1 WO 2017048051A1 KR 2016010336 W KR2016010336 W KR 2016010336W WO 2017048051 A1 WO2017048051 A1 WO 2017048051A1
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Prior art keywords
extract
sanjoin
yang
composition
disease
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PCT/KR2016/010336
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English (en)
Korean (ko)
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조영우
류종훈
장대식
정인호
이형은
류별
Original Assignee
경희대학교 산학협력단
대화제약 주식회사
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Publication of WO2017048051A1 publication Critical patent/WO2017048051A1/fr

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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
    • 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)
    • A61K36/34—Campanulaceae (Bellflower family)
    • A61K36/344—Codonopsis
    • 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)
    • A61K36/72—Rhamnaceae (Buckthorn family), e.g. buckthorn, chewstick or umbrella-tree

Definitions

  • the present invention relates to a pharmaceutical composition for the prevention or treatment of cognitive dysfunction or degenerative brain disease, including Sanjoin extract and Yang Yugeun extract.
  • Alzheimer's disease is the most common degenerative brain disease that causes dementia. It is characterized by a slow onset and progressive progression. Symptoms of Alzheimer's dementia include not only cognitive decline but also mental behaviors such as personality changes, nervousness, depression, delusions, hallucinations, aggressiveness, and sleep disorders. In the late stages of Alzheimer's dementia, neurological disorders such as stiffness and gait abnormality appear, and physical disorders such as fecal incontinence, infection, and pressure sores appear. Alzheimer's dementia is classified as premature (elderly) Alzheimer's dementia under 65 years of age, and late-stage (old age) Alzheimer's dementia under 65 years of age.
  • Alzheimer's dementia has been reported to occur in a relatively young group, and is the most common form of dementia in the elderly population, with the incidence doubled with every five years of age in the 65-85 range. have. In 2009, the number of deaths from Alzheimer's disease among the total elderly population was reported to have increased by 47% compared to 2000. The medical expenditures of families with Alzheimer's dementia patients were higher than those of families with other forms of dementia. It is about 3.2 times. Alzheimer's dementia is a passive method of accommodating patients, so the importance of developing therapies is increasing. When examining brain tissues of Alzheimer's dementia, senile plaques, neurofibrillary tangles, and neuronal cell death can be observed.
  • Alzheimer's dementia The exact pathogenesis and cause of Alzheimer's dementia is unknown, but at present, the imbalance of neurotransmitters and the excessive production of amyloid ⁇ protein in the brain, resulting in toxicity in the brain, is the key mechanism of the pathogenesis.
  • hyperphosphorylation of tau protein, neuroinflammation, and oxidative substances cause brain cell damage, which is known to cause Alzheimer's dementia.
  • acetylcholinesterase inhibitors that increase the amount of acetylcholine in the brain by preventing the degradation of acetylcholine, a neurotransmitter recognized in Alzheimer's dementia, have attracted attention.
  • Drugs that are currently developed and used as a treatment for dementia with FDA approval include tacrine, donepezil, galanthamine, and rivastigmine, all of which are acetylcholinesterase inhibitors or diseases. Efforts have been made to develop drugs to slow the progression and to treat the underlying causes of Alzheimer's dementia because they have little effect on direct treatment and have a limited range of treatment at the outset.
  • vascular dementia is mostly caused by a lack of blood supply to various parts of the brain due to cerebrovascular arteriosclerosis and damage to brain cells.
  • vascular dementia and Alzheimer's dementia have different causes, but the same is true in that damage occurs in memory and learning ability.
  • the present inventors have been researching to develop an effective therapeutic agent for preventing and treating cognitive dysfunction and degenerative brain disease, and have found a complex herbal extract that can effectively enhance memory and learning ability, Completed.
  • An object of the present invention is to provide a pharmaceutical composition for the prevention or treatment of cognitive dysfunction or degenerative brain disease, including Sanjoin extract and Yang yugeun extract.
  • the present invention provides a pharmaceutical composition for the prevention or treatment of cognitive dysfunction or degenerative brain disease, including Sanjoin extract and Yang yugeun extract.
  • Sanjoin in the present invention is Zizypus jujuba var. spinosa
  • the acid extract refers to a material obtained by separating from Sanjoin.
  • the acid extract may be prepared using a conventional extraction solvent known in the art, for example, water, C 1-4 alcohol (eg, methanol, ethanol, butanol, etc.), or a mixed solvent of the alcohol and water.
  • a conventional extraction solvent known in the art, for example, water, C 1-4 alcohol (eg, methanol, ethanol, butanol, etc.), or a mixed solvent of the alcohol and water.
  • the acid extract of the present invention is Zizypus jujuba var. ethanol or water extract of spinosa . More preferably, the acid extract of the present invention is Zizypus jujuba var. 10-95 % ethanol extract of spinosa .
  • Sanjoin extract is used for the purpose of the present invention for the prevention, treatment or amelioration of cognitive dysfunction or degenerative brain disease.
  • Sanjoin extract in the present invention may be obtained by using a commercially available, or may be obtained by using a method known in the art that is collected or grown in nature, but is not limited thereto.
  • the root of lanceolata refers to the root extract, and the root extract is a substance obtained by separating from the roots.
  • the yang yugeun extract is a conventional extracting solvent known in the art, such as water, C 1-4 alcohol (eg methanol, ethanol, butanol, etc.), or using a mixed solvent of the alcohol and water, etc. Refers to a material obtained from separation.
  • the Yang yang-geun extract of the present invention is Codonopsis lanceolata is an ethanol or water extract. More preferably, the Yanggeuneun extract of the present invention is Codonopsis 10-95 % ethanol extract of lanceolata .
  • Yang Yugeun Yang Yugeun extract is used for the prevention, treatment or improvement of cognitive dysfunction or degenerative brain disease.
  • Yang Yu-geun extract in the present invention may be obtained by using a commercially available, or obtained by using a method known in the art that is harvested or grown in nature, but is not limited thereto.
  • Sanjoin extract and Yang Yu-geun extract of the present invention may be prepared separately, mixed and blended to prepare a composition, or may be prepared as a composite extract by extracting together Sanjoin and Yang-yu root.
  • the Sanjoin extract and Yang Yu-geun extract of the present invention is a complex extract of Sanjoin and Yang Yu-geun.
  • the extract of Sanjoin or Yogurt according to the present invention may be obtained by cutting and / or crushing Sanjoin or Yokan root, and then water in a volume of about 2 to 20 times the weight of the prepared Sanjoin or Yokan root, or methanol, ethanol, butanol, and the like.
  • an extraction method such as hot water extraction, cold needle extraction, reflux extraction, or ultrasonic extraction for 15 days, it is filtered, concentrated and dried according to a conventional method, Lamb's root extract can be obtained.
  • the composite extract of Sanjoin and Yang Yu-geun according to the present invention is pulverized and mixed with Sanjoin and Yang-Yu-Keun in a grinder, and then extracted by refluxing at 75-80 ° C. by adding ethanol corresponding to 5 times the weight, and weighing the residue 4 After adding reflux to ethanol at 75 ⁇ 80 °C and extract the reflux and filtered, all the extracts were combined under reduced pressure and concentrated through a drying process to obtain a composite extract of acid and phosphorus root.
  • the pharmaceutical composition comprising the Sanjoin extract and Yang Yu-geun extract according to the present invention comprises the Sanjoin extract and Yang-Yu-Geun extract in a weight ratio of 1: 1 to 10: 1.
  • the Sanjoin extract and Yanggeun-geun extract of the present invention may be included in a total weight ratio of 1: 1 to 6: 1, more preferably the Sanjoin extract and Yanggeun-geun extract in a weight ratio of 5: 1 in the total composition.
  • the Sanjoin Zizyphus jujuba Mill var. spinosa Hu 's seed and Yang Yu-geun (root of Codonopsis lanceolata ) were weighed in a ratio of 1: 1 to 6: 1 by weight, mixed and crushed, and added by 50% ethanol corresponding to 5 times the total weight to 75-80 The mixture was extracted at reflux for 3 hours, and 4 times ethanol was added to the residue, followed by extraction under reflux for 3 hours at 75 to 80 ° C., followed by filtration. Then, all the extracts were combined, concentrated under reduced pressure, and dried to prepare a composite extract of Sanjoin and Yang Yu-geun.
  • the pharmaceutical composition comprising the sanjoin extract of the present invention and the Yanggeun root extract can be usefully used for the prevention or treatment of cognitive dysfunction or degenerative brain disease.
  • the cognitive dysfunction is a disorder showing cognitive impairment and behavioral change in an animal with normal function, and refers to a disease resulting from a decrease in function such as memory, spatial perception, judgment, executive function, and language ability.
  • the cognitive dysfunction may be dementia due to various causes, such as Alzheimer's disease, vascular dementia, other alcoholism, trauma, dementia resulting from Parkinson's disease, or forgetfulness. And preferably vascular dementia or Alzheimer's dementia.
  • degenerative brain disease is a disease that occurs in the brain caused by the destruction of nerve cells, for example, stroke, stroke, forgetfulness, dementia, Alzheimer's disease, Parkinson's disease or Huntington's disease.
  • Prevention in the present invention means any action that inhibits or delays the development of cognitive dysfunction or degenerative brain disease by administration of a composition comprising a composite extract of Sanjoin extract and Yang Yu-geun extract according to the present invention as an active ingredient.
  • the treatment refers to all the activities in which the symptoms of cognitive dysfunction or degenerative brain disease are improved or beneficially administered by administration of a composition comprising a composite extract of sanjoin extract and lamb's root extract according to the present invention as an active ingredient.
  • the Sanjoin and Yang Yu-geun complex extracts of the present invention were administered to a memory impaired animal model induced with scopolamine or beta-amyloid protein, and manual evacuation experiments, Y-maze experiments, and Morris underwater maze experiments were performed. .
  • the present invention is to administer a pharmaceutical composition comprising a sanjoin extract and Yanggeuneun extract according to the present invention to an animal including a human in need thereof to prevent or treat cognitive dysfunction or degenerative brain disease Provide a method.
  • the subject refers to all animals including humans that may have already developed or may develop cognitive dysfunction or degenerative brain disease, and by administering the composition of the present invention to the subject, the disorder or disease may be effectively prevented and treated. .
  • the composition of the present invention is administered in a pharmaceutically effective amount.
  • the pharmaceutically effective amount means an amount sufficient to treat the disease at a reasonable benefit / risk ratio applicable to the medical treatment in the medical treatment, and the effective dose level refers to the type and severity of the individual, age, sex, and activity of the drug. , Drug sensitivity, time of administration, route of administration and rate of release, duration of treatment, factors including concurrently used drugs, and other factors well known in the medical arts.
  • the compositions of the present invention may be administered as individual therapeutic agents or in combination with other therapeutic agents and may be administered sequentially or simultaneously with conventional therapeutic agents. And single or multiple administrations. Taking all of the above factors into consideration, it is important to administer an amount that can obtain the maximum effect in a minimum amount without side effects, and can be easily determined by those skilled in the art.
  • the preferred dosage of the composition of the present invention is to administer the combined extract of Sanjoin and Yanggeuneun 0.5 g / kg to 1 g / kg per day. Administration may be administered once a day or may be divided several times. The dosage does not limit the scope of the invention in any aspect.
  • the pharmaceutical composition comprising the sanjoin extract of the present invention and the yangeungeun extract may include the extract in an amount of 0.1 to 50% by weight based on the total weight of the composition, but is not limited thereto.
  • composition of the present invention can be administered to mammals such as rats, mice, livestock, humans, etc. by various routes. All modes of administration can be expected, for example, by oral, rectal or intravenous, intramuscular, subcutaneous, intrauterine dural or intracerebroventricular injection.
  • compositions of the present invention may further comprise suitable additives commonly used in the manufacture of pharmaceutical compositions, such as carriers, excipients and diluents.
  • compositions of the present invention can be used in the form of powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols and the like, oral formulations, external preparations, suppositories, and sterile injectable solutions, respectively, according to conventional methods.
  • Carriers, excipients and diluents that may be included in the composition comprising the extract include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate , Cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil.
  • Solid preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, and the solid preparations may include at least one excipient such as starch, calcium carbonate, sucrose in the extract. ) Or lactose, gelatin and the like are mixed.
  • lubricants such as magnesium styrate talc are also used.
  • Oral liquid preparations include suspending agents, liquid solutions, emulsions, and syrups, and may include various excipients, such as wetting agents, sweeteners, fragrances, and preservatives, in addition to commonly used simple diluents such as water and liquid paraffin.
  • Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, suppositories.
  • the non-aqueous solvent and suspending agent propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like can be used.
  • As the base of the suppository witepsol, macrogol, tween 61, cacao butter, laurin butter, glycerogelatin and the like can be used.
  • the present invention provides a dietary supplement or food composition for the prevention or improvement of cognitive impairment or degenerative brain disease, including Sanjoin extract and Yang yugeun extract.
  • the Sanjoin, Sanjoin Extract, Yang Yu-geun, Yang Yu-geun Extract, cognitive dysfunction, degenerative brain disease are as described above.
  • the extract of Sanjoin in the dietary supplement composition according to the present invention is Zizypus jujuba var. spinosa may be an ethanol or water extract, and the larvae extract is Codonopsis It may be an ethanol or water extract of lanceloata .
  • the extract of Sanjoin and Yang yugeun in the nutraceutical composition according to the present invention are included in the total composition in a weight ratio of 1: 1 to 10: 1, more preferably 1: 1 to 6: 1, particularly preferably 5: 1. Can be.
  • the improvement includes the treatment, alleviation, and prevention of symptoms, and in the present invention, cognitive dysfunction and degenerative brain diseases, such as stroke, stroke, forgetfulness, dementia, Alzheimer's disease, Parkinson's disease or Huntington's disease, Treated, alleviated or prevented.
  • cognitive dysfunction and degenerative brain diseases such as stroke, stroke, forgetfulness, dementia, Alzheimer's disease, Parkinson's disease or Huntington's disease, Treated, alleviated or prevented.
  • Sanjoin extract and Yangyanggeun extract in the dietary supplement composition or food composition comprising Sanjoin extract and Yanggeun root extract of the present invention, depending on the purpose of use, formulation, formulation, as long as it can exhibit an improvement effect of cognitive dysfunction or degenerative brain disease It may be included in an amount (effective amount).
  • an effective amount refers to an amount of an effective ingredient capable of inducing an improvement effect of cognitive dysfunction or degenerative brain disease. Such effective amounts can be determined experimentally within the range of ordinary skill in the art.
  • the nutraceutical composition or food composition of the present invention is a variety of nutrients, vitamins, minerals (electrolytes), synthetic flavors, such as natural and natural flavors, coloring and neutralizing agents (such as cheese, chocolate), pectic acid and salts thereof , Alginic acid and salts thereof, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohols, carbonation agents used in carbonated drinks and the like. Others may contain pulp for the production of natural fruit juices and fruit juice drinks and vegetable drinks. These components can be used independently or in combination.
  • nutraceutical composition or food composition of the present invention is in various forms of food or beverage, for example meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, gum, ice cream, soup, beverage, tea It may be in the form of any one of functional water, drink, alcoholic beverage and vitamin complex, and may be used in the form of powder, granules, tablets, capsules, or liquids.
  • Sanjoin and yangeungeun complex extract of the present invention may be added to food or beverage for the purpose of preventing and improving diseases related to cognitive dysfunction or degenerative brain disease.
  • the amount of the complex extract in the food or beverage can be added usually in 1 to 5% by weight of the total food composition weight, the beverage composition is 0.02 to 10 g, preferably 0.3 to 1 g based on 100 ml Can be added.
  • the beverage composition in addition to containing the complex extract as an essential ingredient in the indicated ratio, there is no particular limitation as a liquid component and may contain various flavors or natural carbohydrates, etc. as an additional ingredient as a general beverage.
  • natural carbohydrates are monosaccharides such as disaccharides such as glucose and fructose, for example polysaccharides such as maltose and sucrose, for example conventional sugars such as dextrin, cyclodextrin and the like xylitol And sugar alcohols such as sorbitol and erythritol.
  • natural flavors tauumatin, stevia extracts (e.g.
  • the proportion of said natural carbohydrates is generally about 1-20 g, preferably about 5-12 g per 100 mL of the composition of the present invention.
  • the health functional food composition may further include a food additive, and the suitability as a food additive, unless otherwise specified in accordance with the General Regulations of the Food Additives Code and General Test Law approved by the Ministry of Food and Drug Safety, etc. Judging by the standards and standards.
  • Items listed in the "Food Additives Code” include, for example, chemical synthetic products such as ketones, glycine, potassium citrate, nicotinic acid, cinnamon acid, natural additives such as navy, licorice extract, crystalline cellulose, guar gum, L- Mixed preparations, such as a glutamate sodium preparation, a noodles addition alkali preparation, a preservative preparation, and a tar pigment preparation, are mentioned.
  • chemical synthetic products such as ketones, glycine, potassium citrate, nicotinic acid, cinnamon acid, natural additives such as navy, licorice extract, crystalline cellulose, guar gum, L- Mixed preparations, such as a glutamate sodium preparation, a noodles addition alkali preparation, a preservative preparation, and a tar pigment preparation, are mentioned.
  • Complex extract according to the present invention is added to the food containing a beverage in the process of manufacturing the health functional food can be appropriately added or reduced the content as needed.
  • the present invention comprises administering the above-described pharmaceutical composition or food composition to a subject in need of prevention, improvement or treatment of cognitive dysfunction or degenerative brain disease, Provide methods of prevention, improvement or treatment.
  • the subject comprises a mammal, in particular a human.
  • the present invention also provides the use of the above-described pharmaceutical composition or food composition for the manufacture of a medicament or food for the prevention, improvement or treatment of cognitive impairment or degenerative brain disease.
  • the cognitive dysfunction or degenerative brain disease is the same as described above in the present specification.
  • composition comprising a composite extract of the Sanjoin extract and Yang Yu-geun extract of the present invention can significantly improve learning and memory, effectively preventing, treating and improving cognitive dysfunction or degenerative brain disease.
  • Figure 1 shows the results of measuring the time to enter the dark room in the dose-dependent (50, 100, 200 and 400 mg / kg) administered to the memory decay animals induced by the scopolamine induced sanjoin 50% ethanol extract The graph shown.
  • Figure 2 is a dose-dependent (25, 50, 100 and 200 mg / kg) administered to the scopolamine-induced memory loss animals with sheep root 50% ethanol extract and measured the time to enter the dark room in the passive avoidance experiment The graph shown.
  • FIG. 3 compares the improvement effect on memory loss in scopolamine-induced memory loss of a single extract of Sanjoin and Yang-Yang Root and the complex extract of Sanjoin-Yang-Yang Root when administered at the same concentration (100 mg / kg). This graph shows the results of measuring the time to enter the dark room in the avoidance experiment.
  • FIG. 5 is a dose-dependent (50, 100, 200 and 400 mg / kg) administration of scopolamine-induced memory deprivation animals with a 5: 1 weight ratio complex extract of Sanjoin and Yang Yu-geun and altered behavior and total in the Y-maze experiment. It is a graph showing the result of measuring entrance and exit.
  • FIG. 6 shows the results of measuring the time to find the platform in the training experiment of Morris water maze experiment with Sanjoin and Yang Yu-geun 5: 1 weight ratio complex extracts administered with scopolamine-induced memory loss animals. Is a graph.
  • FIG. 8 is a dose-dependent (50, 100, 200 and 400 mg / kg) administration of scopolamine-induced memory deprivation animals with sanjoin and yang-geun 5: 1 weight ratio complex extracts. It is a graph showing the result of measuring the number.
  • Scopolamine and donepezil were purchased from Sigma-Aldrich Chemistry Co., and beta amyloid was purchased from American Peptide Co., and other reagents were commercially available.
  • Sanjoin Zizyphus
  • jujuba Mill var. spinosa Hu 's Seed or Yang Yu-geun ( Codonopsis) roots of lanceolata ) were weighed at a weight ratio of 1: 1 to 6: 1. Then, the weighed Sanjoin and Yang Yu-geun were crushed and mixed with a grinder, and 50% ethanol corresponding to 5 times the total weight was added and extracted under reflux for 3 hours at 75 to 80 ° C. The mixture was filtered after reflux extraction at 80 ° C. for 3 hours. Thereafter, the extracts were combined, concentrated under reduced pressure, and dried to prepare a composite extract of Sanjoin and Yang Yu-geun.
  • Sanjoin Zizyphus
  • jujuba Mill var. spinosa Hu 's Seed or Yang Yu-geun ( Codonopsis) roots of lanceolata ) were weighed each to 100 g weight. Then, the weighed Sanjoin or Yang Yu-geun was crushed and mixed with a grinder, and 50% ethanol corresponding to 5 times the total weight was added and extracted under reflux for 3 hours at 75 to 80 ° C. The mixture was filtered after reflux extraction at 80 ° C. for 3 hours. Thereafter, all the extracts were combined, concentrated under reduced pressure, and dried to prepare a single extract of Sanjoin and Yang Yu-geun.
  • mice Six-week-old ICR mice (26-28 g) were supplied from Orient Co., Ltd. (Seoul, Korea) and used for 5 days in an animal laboratory at the College of Pharmacy, Kyung Hee University. (23 ⁇ 2 ° C.), humidity (50 ⁇ 10%) and contrast period (12 hours) were allowed to adjust automatically.
  • the experiment was conducted using 10 mice prepared for each drug administration group and control group.
  • Sanjoin extract and Yang Yu-geun extract prepared in Reference Example 1 as a drug-administered group and the composite extract of Sanjoin and Yang-yu-geun (Sanjo: Yang Yoo-keun 1: 1, 2: 1, 3: 1, 4: 1, 5: 1) And 6: 1 weight ratio) was dissolved in 0.5% CMC (carboxymethylcellulose: Sigma, USA) and orally administered to the mouse of Reference Example 2.
  • CMC carboxymethylcellulose: Sigma, USA
  • Control group 1 was administered 5 mg / kg of donepezil, control group 2 was not administered drug, control group 3 was administered only 10% CMC.
  • mice 30 minutes after the drug administration, scopolamine dissolved in 0.9% physiological saline was administered intraperitoneally at a dose of 1 mg / kg in the drug administration group, the control groups 1 and 2 (Ebert, U. et al., Eur. J. Clin. Invest , 28, pp 944-949, 1998).
  • the mice were placed in the illuminated bright compartment and after 10 seconds of exploration the guillotin door was opened to enter the dark compartment. Mice that did not enter the dark side within 60 seconds after the guillotine door was opened were excluded from the experiment. After the guillotine door was opened, the time until the mouse entered the dark side was measured. Once the mouse enters the dark side, the guillotine door closes and an electric shock of 0.5 mA flows through the bottom of the grid for 3 seconds and the mouse remembers this electrical action.
  • the experiment was conducted 24 hours after the study test. After 10 seconds of search time, the time required for the foot of the guillotine to open and all four feet into the dark side (latency time) was measured up to 300 seconds. The longer the time taken, the better the learning and memory of passive avoidance.
  • the retention time of the scopolamine-only group was 59.10 ⁇ 24.45 seconds in the dose-dependence experiment for the acidic single ethanol extract, whereas 100 mg / 134.2 ⁇ 23.80 ( p ⁇ 0.05) seconds in the kg administration group (drug group 2), 157.8 ⁇ 56.78 ( p ⁇ 0.05) in the 200 mg / kg administration group (drug group 3), 176.5 in the 400 mg / kg administration group (drug group 4) There was a significant increase of ⁇ 48.21 seconds.
  • the retention time of the scopolamine-only group was 22.41 ⁇ 18.93 seconds in the dose-dependence experiment on the yang-geun single ethanol extract 50 mg /
  • Table 3 and FIG. 3 show the results of improving memory for 100 mg / kg of the composite extract of Sanjoin and Yang Yu-geun, which were combined with a single extract of Sanjoin and Yang Yu-geun and various composition ratios.
  • the retention time of the scopolamine-only group (control 2) was 43.40 ⁇ 30.04 seconds
  • the retention time of the group treated with Sanjo single extract (drug group 1) was 174.8 ⁇ 63.78 ( p ⁇ 0.05) seconds
  • the retention time of the group to which the extract was administered was 129.4 ⁇ 37.31 ( p ⁇ 0.05) seconds.
  • the combined extracts of Sanjoin and Yangyu-geun were 159.8 ⁇ 77.52 ( p ⁇ 0.05) when Sanjoin and Yang-Yu-geun were in the ratio of 3: 1 weight (drug group 5). ⁇ 75.54 ( p ⁇ 0.05) seconds, when the sanjoin and sheep roots are at 5: 1 weight fraction (drug group 7) 221.9 ⁇ 44.62 ( p ⁇ 0.05) seconds, when the sanjoin and sheep roots are at 6: 1 weight fraction (drug group 8) In the case of 182.4 ⁇ 60.79 ( p ⁇ 0.05), Sanjoin and Yang Yu-geun had a 5: 1 weight ratio (drug group 7), which showed the best learning and memory improvement effect.
  • the retention time of the scopolamine-only group (Control 2) in the dose-dependent experiment of the 5: 1 weight ratio complex extract of Sanjoin and Yang Yu-geun was 52.89 ⁇ 12.77 sec. 142.0 ⁇ 37.50 ( p ⁇ 0.05) seconds in the 100 mg / kg dose group (drug group 2) of the 5: 1 weight ratio combined extract of both roots and 176.7 ⁇ 66.66 ( p ⁇ 0.05) in the 200 mg / kg group (drug group 3)
  • the 5: 1 weight ratio complex extract of Sanjoin and Yang Yu-geun according to the Example was dissolved in 4 ml of 0.5% CMC (carboxymethylcellulose, Sigma, USA) and then orally administered to mice of Reference Example 2 at 50, 100, 200 and 400 mg / kg. It was. Positive control (control 1) was administered 5 mg / kg of donepezil, control 2 was not administered drug, negative control (control 3) was administered only 0.5% CMC.
  • CMC carboxymethylcellulose, Sigma, USA
  • the 5: 1 weight ratio complex extract of Sanjoin and Yang Yu-geun according to the Example was dissolved in 0.5% CMC and orally administered to the mice of Reference Example 2 at doses of 100, 200 and 400 mg / kg.
  • Positive control control 1 was administered 5 mg / kg of donepezil
  • control 2 was not administered drug
  • negative control control 3) was administered 0.5% CMC.
  • Beta amyloid protein 1-42 fragment (American peptide, USA) was purchased and dissolved in 0.9% saline at a concentration of 1 mg / ml. It was then used after aggregation of beta amyloid protein at 37 °C for 24 hours. After inducing anesthesia with 2% isofluorane in mice of Reference Example 2, 3 ⁇ was administered to the right ventricle using a Hamilton syringe. The negative control group was administered 0.9% saline. The drug was orally administered immediately after the beta amyloid administration, and the drug was administered once a day for a total of 7 days.
  • the experiment was conducted 24 hours after the study test. After 10 seconds of search time, the time required for the guillotine door to open and 4 shots to the dark side (latency time) was measured up to 300 seconds. The longer the time taken, the better the learning and memory of passive avoidance.
  • Beta amyloid protein 1-42 fragment (American peptide, USA) was purchased and dissolved in 0.9% saline at a concentration of 1 mg / ml. It was then used after aggregation of beta amyloid protein at 37 °C for 24 hours. After inducing anesthesia with 2% isofluorane in mice of Reference Example 2, 3 ⁇ was administered to the right ventricle using a Hamilton syringe. The negative control group was administered 0.9% saline. The drug was orally administered immediately after the beta amyloid administration, and the drug was administered once a day for a total of 7 days.
  • Experimental Example 5- (1) was dissolved in 0.5% CMC and Sanjoin and Yang Yu-geun 5: 1 weight ratio complex extract according to the example, orally at various doses (50, 100, 200 and 400 mg / kg) for 7 days. Administered.
  • the positive control (control 1) was orally administered 5 mg / kg of donepezil for 7 days, and the 0.5% CMC was orally administered to the negative control (control 3) for 7 days.
  • control 3 the negative control
  • Y-maze test was performed 24 hours after the last drug administration, and the method was the same as in Experimental Example 2.
  • the spontaneous alternation of the beta-amyloid-only group was 51.61 ⁇ 11.44%
  • the 200: 1 and 400: 1 weight ratio complex extracts of Sanjoin and Yang Yu-geun. / kg administration group showed a significant increase of 63.04 ⁇ 12.37 ( p ⁇ 0.05) and 64.71 ⁇ 9.397 ( p ⁇ 0.05)%, respectively.
  • there was no change in the total entry indicating the total number of entrances to each zone, indicating that the spontaneous alternation was not caused by the change in the activity of the mouse.
  • the above ingredients are mixed and filled in an airtight cloth to prepare a powder.
  • tablets are prepared by tableting according to a conventional method for preparing tablets.
  • the above ingredients are mixed and filled into gelatin capsules to prepare capsules.
  • the amount of the above ingredient is prepared per ampoule (2 ml).
  • each component is added to the purified water to dissolve it, the lemon flavor is appropriately added, the above components are mixed, purified water is added, the whole is adjusted to 100 ml by the addition of purified water, and then filled in a brown bottle.
  • the solution is prepared by sterilization.
  • Vitamin B6 0.5 mg
  • composition ratio of the above-mentioned vitamin and mineral mixtures is mixed with a component suitable for a health food in a preferred embodiment, the compounding ratio may be arbitrarily modified, and the above ingredients are mixed according to a conventional health food manufacturing method.
  • the granules may be prepared and used for preparing a health food composition according to a conventional method.
  • composition ratio is mixed with a relatively suitable component for a preferred beverage in a preferred embodiment
  • compounding ratio may be arbitrarily modified according to regional and ethnic preferences such as demand hierarchy, main country, and usage.
  • composition comprising the Sanjoin extract and Yang Yu-geun extract of the present invention can be usefully used for the prevention, improvement or treatment of cognitive dysfunction or degenerative brain disease.

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Abstract

La présente invention concerne une composition pharmaceutique destinée à prévenir ou à traiter les troubles de la fonction cognitive ou les maladies dégénératives du cerveau, qui contient un extrait de Zizyphus spinosi et un extrait de racine de Codonopsis lanceolata.
PCT/KR2016/010336 2015-09-18 2016-09-13 Composition pharmaceutique destinée à prévenir ou à traiter les troubles de la fonction cognitive ou les maladies dégénératives du cerveau WO2017048051A1 (fr)

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KR101877860B1 (ko) * 2017-05-16 2018-07-13 한국과학기술연구원 참빗살나무 추출물을 포함하는 인지장애 관련 질환의 예방 또는 치료용 조성물

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KR20050047779A (ko) * 2003-11-18 2005-05-23 주식회사 에스티씨나라 생약 추출물을 유효 성분으로 포함하는 치매 예방 또는치료 및 인지 기능 개선용 조성물
KR20050092292A (ko) * 2004-03-15 2005-09-21 주식회사 크라우젠 기억력 증강 효과가 있는 생약재 조성물
KR20120053604A (ko) * 2010-11-18 2012-05-29 강원대학교산학협력단 더덕 추출물을 포함하는 허혈성 뇌혈관 질환 예방 또는 개선용 조성물
KR20130001764A (ko) * 2011-06-28 2013-01-07 삼성중공업 주식회사 선박용 배관 클램프
KR20140077382A (ko) * 2012-12-14 2014-06-24 경희대학교 산학협력단 란세마사이드 ａ 또는 이의 대사체를 함유하는 인지기능 장애 예방 또는 치료용 약학조성물

Patent Citations (5)

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Publication number Priority date Publication date Assignee Title
KR20050047779A (ko) * 2003-11-18 2005-05-23 주식회사 에스티씨나라 생약 추출물을 유효 성분으로 포함하는 치매 예방 또는치료 및 인지 기능 개선용 조성물
KR20050092292A (ko) * 2004-03-15 2005-09-21 주식회사 크라우젠 기억력 증강 효과가 있는 생약재 조성물
KR20120053604A (ko) * 2010-11-18 2012-05-29 강원대학교산학협력단 더덕 추출물을 포함하는 허혈성 뇌혈관 질환 예방 또는 개선용 조성물
KR20130001764A (ko) * 2011-06-28 2013-01-07 삼성중공업 주식회사 선박용 배관 클램프
KR20140077382A (ko) * 2012-12-14 2014-06-24 경희대학교 산학협력단 란세마사이드 ａ 또는 이의 대사체를 함유하는 인지기능 장애 예방 또는 치료용 약학조성물

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