WO2017048051A1 - Pharmaceutical composition for preventing or treating cognitive function disorder or degenerative brain disease - Google Patents

Pharmaceutical composition for preventing or treating cognitive function disorder or degenerative brain disease Download PDF

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Publication number
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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French (fr)
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/en

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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

The present invention relates to a pharmaceutical composition for preventing or treating cognitive function disorder or degenerative brain disease, which includes Zizyphus spinosi extract and Codonopsis lanceolata root extract.

Description

인지기능장애 또는 퇴행성 뇌질환의 예방 또는 치료용 약학적 조성물Pharmaceutical composition for the prevention or treatment of cognitive dysfunction or degenerative brain disease
본 발명은 산조인 추출물 및 양유근 추출물을 포함하는 인지기능장애 또는 퇴행성 뇌질환의 예방 또는 치료용 약학적 조성물에 관한 것이다.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.
전 세계가 빠른 속도로 고령화 사회로 진입하고 있으며, 이에 따라 인간은 질병없이 건강하게 장수할 수 있는 높은 삶의 질을 추구하고 있다. 과학의 발달로 인한 수명의 연장으로 노인 인구가 증가하면서, 신경퇴행성 질환인 치매 환자의 비율이 급증하고 있다.The world is rapidly entering an aging society, and as a result, humans are pursuing a high quality of life that can be healthy and healthy without disease. As the age of the elderly grows due to the extension of life span due to the development of science, the proportion of dementia patients with neurodegenerative diseases is increasing rapidly.
알츠하이머성 치매(Alzheimer's disease)는 치매를 일으키는 가장 흔한 퇴행성 뇌질환으로, 이 병의 특징은 서서히 발병하여 점차적으로 계속 진행되는 것이다. 알츠하이머성 치매의 증상은 인지기능 저하뿐만 아니라 성격변화, 초조함, 우울증, 망상, 환각, 공격성, 수면 장애 등의 정신행동이 나타난다. 알츠하이머성 치매의 말기에 이르면 경직, 보행 이상 등의 신경학적 장애가 나타나고 대소변 실금, 감염, 욕창 등 신체적인 장애도 나타난다. 알츠하이머성 치매는 발병 연령에 따라 65세 미만에서는 조발성(초로기) 알츠하이머성 치매, 65세 이상에서는 만발성(노년기) 알츠하이머성 치매으로 구분한다. 알츠하이머형 치매는 비교적 젊은 층에서도 발병하는 사례가 보고된 바 있으며, 65세에서 85세 범위 내에서는 나이가 5세 증가할 때마다 발병률이 2배씩 높아지는 등 노인 인구의 치매 유형 중 가장 흔한 형태로 알려져 있다. 2009년 전체 노인 인구의 사망자 중 알츠하이머형 치매로 사망한 환자가 2000년 대비 약 47% 증가하였다고 보고되고 있으며 알츠하이머형 치매 환자가 있는 가정의 의료비 지출은 다른 형태의 치매환자가 있는 가정의 의료비 지출보다 약 3.2배 정도인 것으로 나타나고 있다. 알츠하이머형 치매는 환자를 수용하는 수동적인 방법으로는 사회 경제적 부담을 감당할 수가 없기 때문에 치료요법 개발의 중요성이 한층 대두되고 있는 실정이다. 알츠하이머성 치매 환자의 뇌 조직을 검사하였을 때 노인반(senile plaque), 신경원섬유 다발(neurofibrillary tangle), 그리고 신경세포의 사멸(neuronal cell death)을 관찰할 수 있다. 알츠하이머성 치매의 정확한 발병 기전과 원인에 대해서는 알려져 있지 않지만, 현재는 신경전달물질(neurotransmitters)의 불균형과 베타 아밀로이드 단백질(amyloid β protein)이 과도하게 만들어져 뇌에 침착되면서 독성을 일으키는 것이 발병의 핵심 기전으로 알려져 있다. 그 외에도 타우 단백질(tau protein)의 과인산화, 신경염증(neuroinflammation), 산화적 물질 등이 뇌 세포 손상을 일으키는 것이 알츠하이머성 치매의 발병 원인으로 알려져 있다.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. The exact pathogenesis and cause of Alzheimer's dementia is unknown, but at present, the imbalance of neurotransmitters and the excessive production of amyloid β protein in the brain, resulting in toxicity in the brain, is the key mechanism of the pathogenesis. Known as In addition, hyperphosphorylation of tau protein, neuroinflammation, and oxidative substances cause brain cell damage, which is known to cause Alzheimer's dementia.
알츠하이머형 치매 치료제로서 현재 가장 진전되어 있는 것이 콜린계 약물이다. 그중에서도 알츠하이머형 치매에서 인식된 신경전달물질인 아세틸콜린의 분해를 방지하여 뇌내의 아세틸콜린의 양을 증가시키는 아세틸콜린에스테라아제(acetylcholinesterase) 저해제가 주목받고 있다.The most advanced drug for treating Alzheimer's dementia is cholinergic drugs. Among them, 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.
현재 FDA 승인을 받아 치매치료제로 개발되어 사용되고 있는 의약품은 타크린(tacrine), 도네페질(donepezil), 갈란타민(galanthamine), 리바스티그민(rivastigmine) 등이 있는데 이들은 모두 아세틸콜린에스테라아제 저해제이나 병의 진행을 늦출 뿐 직접적인 치료에는 별 효과가 없고 또한 발병 초기에 제한된 치료 범위를 가지고 있기 때문에 알츠하이머형 치매의 근본적인 원인을 치료하는 약을 개발하고자 하는 노력이 이루어져 왔다.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.
또한, 혈관성 치매는 대부분 뇌혈관 동맥경화에 의해 뇌의 여러 곳에 혈액공급이 부족하게 되어 뇌세포에 손상을 입음으로써 발생한다. 혈관성 치매와 상기 알츠하이머성 치매는 발생 원인은 다르지만, 결과적으로 기억력 및 학습능력에 손상이 발생한다는 점에 있어서는 동일하다.In addition, 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.
이러한 배경 하, 본 발명자들은 인지기능장애 및 퇴행성 뇌질환을 예방 및 치료하기 위한 효과적인 치료제를 개발하기 위하여 연구하던 중, 기억력 및 학습능력을 효과적으로 증진시킬 수 있는 복합 생약 추출물을 발견하고, 본 발명을 완성하였다.Under these circumstances, 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.
본 발명의 목적은 산조인 추출물 및 양유근 추출물을 포함하는 인지기능장애 또는 퇴행성 뇌질환의 예방 또는 치료용 약학적 조성물을 제공하기 위한 것이다.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.
또한, 본 발명의 목적은 산조인 추출물 및 양유근 추출물을 포함하는 인지기능장애 또는 퇴행성 뇌질환의 예방 또는 개선용 건강기능식품 조성물 또는 식품 조성물을 제공하기 위한 것이다.It is also an object of the present invention to provide a health functional food composition or food composition for the prevention or improvement of cognitive dysfunction or degenerative brain disease, including Sanjoin extract and Yang Yugeun extract.
상기 목적을 달성하기 위한 하나의 양태로서, 본 발명은 산조인 추출물 및 양유근 추출물을 포함하는 인지기능장애 또는 퇴행성 뇌질환의 예방 또는 치료용 약학적 조성물을 제공한다.As one aspect for achieving the above object, 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.
본 발명에서 산조인은 Zizypus jujuba var. spinosa Hu의 씨를 말하며, 산조인 추출물은 산조인으로부터 분리하여 얻은 물질을 의미한다. 구체적으로 산조인 추출물은 당업계에 공지된 통상적인 추출용매, 예를 들어 물, C1-4 알코올(예: 메탄올, 에탄올, 부탄올 등), 또는 상기 알코올과 물과의 혼합용매 등을 사용하여 산조인으로부터 분리하여 얻은 물질을 의미한다.Sanjoin in the present invention is Zizypus jujuba var. spinosa Refers to the seed of Hu , Sanjoin extract refers to a material obtained by separating from Sanjoin. Specifically, 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. Refers to a material obtained from separation.
바람직하게 본 발명의 산조인 추출물은 Zizypus jujuba var. spinosa의 에탄올 또는 수 추출물이다. 보다 바람직하게 본 발명의 산조인 추출물은 Zizypus jujuba var. spinosa의 10 내지 95% 에탄올 추출물이다.Preferably 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 .
본 발명의 목적상 산조인, 산조인 추출물은 인지기능장애 또는 퇴행성 뇌질환의 예방, 치료 또는 개선용으로 사용된다.Sanjoin, Sanjoin extract is used for the purpose of the present invention for the prevention, treatment or amelioration of cognitive dysfunction or degenerative brain disease.
본 발명에서 산조인 추출물은 상업적으로 판매되는 것을 구입하여 사용하거나, 자연에서 채취 또는 재배된 것을 당업계에 공지된 방법으로 처리하여 수득하여 사용할 수 있으나, 이에 제한되지 않는다.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.
본 발명에서 양유근은 Codonopsis lanceolata의 뿌리를 말하며, 양유근 추출물은 양유근으로부터 분리하여 얻은 물질을 의미한다. 구체적으로 양유근 추출물은 당업계에 공지된 통상적인 추출용매, 예를 들어 물, C1-4 알코올(예: 메탄올, 에탄올, 부탄올 등), 또는 상기 알코올과 물과의 혼합용매 등을 사용하여 양유근으로부터 분리하여 얻은 물질을 의미한다.Yang Yu-geun in the present invention is Codonopsis The root of lanceolata refers to the root extract, and the root extract is a substance obtained by separating from the roots. In particular, 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.
바람직하게 본 발명의 양유근 추출물은 Codonopsis lanceolata의 에탄올 또는 수 추출물이다. 보다 바람직하게 본 발명의 양유근 추출물은 Codonopsis lanceolata의 10 내지 95% 에탄올 추출물이다.Preferably, 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 .
본 발명의 목적상 양유근, 양유근 추출물은 인지기능장애 또는 퇴행성 뇌질환의 예방, 치료 또는 개선용으로 사용된다.For the purposes of the present invention, Yang Yugeun, Yang Yugeun extract is used for the prevention, treatment or improvement of cognitive dysfunction or degenerative brain disease.
본 발명에서 양유근 추출물은 상업적으로 판매되는 것을 구입하여 사용하거나, 자연에서 채취 또는 재배된 것을 당업계에 공지된 방법으로 처리하여 수득하여 사용할 수 있으나, 이에 제한되지 않는다.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.
본 발명의 산조인 추출물 및 양유근 추출물은 별도로 제조한 후 혼합, 배합하여 일 조성물로 제조하거나, 또는 산조인 및 양유근을 함께 추출하여 복합추출물로 제조할 수 있다. 바람직하게, 본 발명의 산조인 추출물 및 양유근 추출물은 산조인 및 양유근의 복합추출물이다.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. Preferably, the Sanjoin extract and Yang Yu-geun extract of the present invention is a complex extract of Sanjoin and Yang Yu-geun.
예시적으로, 본 발명에 따른 산조인 또는 양유근 추출물은 산조인 또는 양유근을 절단 및/또는 마쇄한 후, 준비된 산조인 또는 양유근 시료 중량의 약 2 내지 20배에 달하는 부피의 물, 또는 메탄올, 에탄올, 부탄올 등과 같은 C1-C4의 저급 알코올의 극성 용매 또는 상기 물과 C1-C4 저급 알코올의 약 1:0.1 내지 1:10의 혼합비를 갖는 혼합용매로, 20℃ 내지 90℃에서 약 1시간 내지 15일 동안 열수 추출, 냉침 추출, 환류 추출 또는 초음파 추출 등의 추출방법을 사용하여 2 내지 5회, 바람직하게는 2 내지 3회 추출한 후에, 이를 통상의 방법에 따라 여과, 농축 및 건조하여 산조인 또는 양유근 추출물을 수득할 수 있다.By way of example, 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. A polar solvent of the same C 1 -C 4 lower alcohol or a mixed solvent having a mixing ratio of about 1: 0.1 to 1:10 of water and C 1 -C 4 lower alcohol, from about 1 hour at 20 ℃ to 90 ℃ After extracting 2 to 5 times, preferably 2 to 3 times using 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.
또한 예시적으로 본 발명에 따른 산조인 및 양유근의 복합 추출물은 산조인 및 양유근을 분쇄기로 분쇄하여 혼합한 후 중량의 5배수에 해당하는 에탄올을 가하여 75~80℃에서 환류 추출하고, 잔사에 중량대비 4배수의 에탄올을 가하여 75~80℃에서 환류 추출 후 여과하고, 추출액을 모두 합하여 감압 농축 후 건조과정을 거쳐 산조인과 양유근의 복합추출물을 수득할 수 있다.Also illustratively, 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 ℃ 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.
본 발명에 따른 산조인 추출물 및 양유근 추출물을 포함하는 약학적 조성물은 전체 조성물 중 산조인 추출물 및 양유근 추출물을 1:1 내지 10:1의 중량비로 포함한다. 바람직하게, 본 발명의 산조인 추출물 및 양유근 추출물은 전체 조성물 중에 1:1 내지 6:1의 중량비, 보다 바람직하게 산조인 추출물 및 양유근 추출물은 전체 조성물 중에 5:1의 중량비로 포함될 수 있다.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. Preferably, 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.
구체적인 일 실시예에서, 산조인(Zizyphus jujuba Mill var. spinosa Hu의 씨) 및 양유근(Codonopsis lanceolata의 뿌리)을 중량대비 1:1에서 6:1의 비율로 칭량하였고, 이를 분쇄하여 혼합하고, 총 중량의 5배수에 해당하는 50% 에탄올을 가하여 75~80℃에서 3시간 환류 추출하였으며, 잔사에 중량대비 4배수의 에탄올을 가하여 75~80℃에서 3시간 동안 환류 추출 후 여과시켰다. 그리고, 추출액을 모두 합하여 감압 농축 후 건조과정을 거쳐 산조인과 양유근의 복합추출물을 제조하였다. In a specific embodiment, 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.
본 발명의 산조인 추출물 및 양유근 추출물을 포함하는 약학적 조성물은 인지기능장애 또는 퇴행성 뇌질환의 예방 또는 치료에 유용하게 사용될 수 있다.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.
본 발명에서 인지기능장애는 정상 기능을 가진 동물에 대하여 인지손상 및 행동 변화를 나타내는 장애로, 기억력, 공간지각력, 판단력, 집행기능, 언어능력 등의 기능 저하로부터 발생되는 질환을 일컫는다. 상기 인지기능장애는 예를 들면, 알츠하이머성 치매(Alzheimer's disease), 혈관성 치매(vascular dementia), 기타 알콜 중독, 외상, 파킨슨병의 후유증으로 오는 치매와 같은 다양한 원인에 기인한 치매이거나 또는 건망증일 수 있으며, 바람직하게는 혈관성 치매 또는 알츠하이머성 치매일 수 있다.In the present invention, 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.
본 발명에서 퇴행성 뇌질환은 뇌신경 세포가 파괴됨으로써 발생하는 뇌에 발생하는 질환으로 예컨대, 뇌졸중, 중풍, 건망증, 치매, 알츠하이머 질환, 파킨슨 질환 또는 헌팅턴 질환일 수 있다. In the present invention, 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.
본 발명에서 예방이란 본 발명에 따른 산조인 추출물 및 양유근 추출물의 복합 추출물을 유효성분으로 포함하는 조성물의 투여로 인지기능장애 또는 퇴행성 뇌질환 발병을 저해 또는 지연시키는 모든 행위를 의미한다.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.
본 발명에서 치료란 본 발명에 따른 산조인 추출물 및 양유근 추출물의 복합 추출물을 유효성분으로 포함하는 조성물의 투여로 인지기능장애 또는 퇴행성 뇌질환의 증세가 호전되거나 이롭게 변경되는 모든 행위를 의미한다.In the present invention, 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.
구체적인 실험예들에서, 본 발명의 산조인 및 양유근 복합 추출물을 스코폴라민 또는 베타-아밀로이드 단백질로 유도한 기억력 손상 동물 모델에 투여하고, 수동회피실험, Y-미로 실험 및 모리스 수중 미로 실험을 수행하였다. 그 결과, 본 발명의 조성물을 미처리한 대조군에 비하여 본 발명의 산조인 및 양유근 복합 추출물을 투여한 약물투여군에서 학습증진 및 공간지각능력이 현저하게 향상됨을 확인하였다. In specific experimental examples, 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. . As a result, it was confirmed that remarkably improved learning and spatial perception ability in the drug administration group administered the sanjoin and yang yugeun complex extract of the present invention compared to the control untreated composition of the present invention.
따라서 다른 하나의 양태로서, 본 발명은 본 발명에 따른 산조인 추출물 및 양유근 추출물을 포함하는 약학적 조성물을 이를 필요로 하는 인간을 포함하는 동물에게 투여하여 인지기능장애 또는 퇴행성 뇌질환을 예방 또는 치료하는 방법을 제공한다. Therefore, in another aspect, 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.
본 발명에서 개체란 인지기능장애 또는 퇴행성 뇌질환이 이미 발병하였거나 발병할 수 있는 인간을 포함한 모든 동물을 의미하고, 본 발명의 조성물을 개체에게 투여함으로써, 상기 장애 또는 질환을 효과적으로 예방 및 치료할 수 있다. In the present invention, 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. .
본 발명의 조성물은 약학적으로 유효한 양으로 투여한다. 본 발명에서 약학적으로 유효한 양이란 의학적 치료에 의학적 치료에 적용 가능한 합리적인 수혜/위험 비율로 질환을 치료하기에 충분한 양을 의미하며, 유효 용량 수준은 개체 종류 및 중증도, 연령, 성별, 약물의 활성, 약물에 대한 민감도, 투여 시간, 투여 경로 및 배출 비율, 치료 기간, 동시 사용되는 약물을 포함한 요소 및 기타 의학 분야에 잘 알려진 요소에 따라 결정될 수 있다. 본 발명의 조성물은 개별 치료제로 투여하거나 다른 치료제와 병용하여 투여될 수 있고 종래의 치료제와는 순차적 또는 동시에 투여될 수 있다. 그리고 단일 또는 다중 투여될 수 있다. 상기 요소를 모두 고려하여 부작용 없이 최소한의 양으로 최대 효과를 얻을 수 있는 양을 투여하는 것이 중요하며, 당업자에 의해 용이하게 결정될 수 있다. The composition of the present invention is administered in a pharmaceutically effective amount. In the present invention, 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.
예시적으로, 본 발명의 조성물의 바람직한 투여량은 산조인 및 양유근의 복합 추출물을 1일 0.5 g/kg 내지 1 g/kg으로 투여하는 것이 좋다. 투여는 하루에 한번 투여할 수도 있고, 수회 나누어 투여할 수 있다. 상기 투여량은 어떠한 면으로든 본 발명의 범위를 한정하는 것은 아니다.By way of example, 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.
본 발명의 산조인 추출물 및 양유근 추출물을 포함하는 약학적 조성물은 전체 조성물 총 중량에 대하여 상기 추출물을 0.1 내지 50 중량%의 함량으로 포함할 수 있으나, 이에 제한되는 것은 아니다. 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.
본 발명의 조성물은 쥐, 생쥐, 가축, 인간 등의 포유동물에 다양한 경로로 투여될 수 있다. 투여의 모든 방식은 예상될 수 있는데, 예를 들면, 경구, 직장 또는 정맥, 근육, 피하, 자궁내 경막 또는 뇌혈관내(intracerebroventricular) 주사에 의해 투여될 수 있다. The 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.
본 발명의 조성물은 약학적 조성물의 제조에 통상적으로 사용하는 적절한 첨가제, 예를 들어 담체, 부형제 및 희석제 등을 더 포함할 수 있다. Compositions of the present invention may further comprise suitable additives commonly used in the manufacture of pharmaceutical compositions, such as carriers, excipients and diluents.
본 발명의 조성물은 각각 통상의 방법에 따라 산제, 과립제, 정제, 캡슐제, 현탁액, 에멀젼, 시럽, 에어로졸 등의 경구형 제형, 외용제, 좌제 및 멸균 주사용액의 형태로 제형화하여 사용될 수 있으며, 추출물을 포함하는 조성물에 포함될 수 있는 담체, 부형제 및 희석제로는 락토즈, 덱스트로즈, 수크로스, 솔비톨, 만니톨, 자일리톨, 에리스리톨, 말티톨, 전분, 아카시아 고무, 알지네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실리케이트, 셀룰로즈, 메틸 셀룰로즈, 미정질 셀룰로스, 폴리비닐 피롤리돈, 물, 메틸히드록시벤조에이트, 프로필히드록시벤조에이트, 탈크, 마그네슘 스테아레이트 및 광물유를 들 수 있다. 제제화할 경우에는 보통 사용하는 충진제, 증량제, 결합제, 습윤제, 붕해제, 계면활성제 등의 희석제 또는 부형제를 사용하여 조제된다. 경구투여를 위한 고형제제에는 정제, 환제, 산제, 과립제, 캡슐제 등이 포함되며, 이러한 고형제제는 상기 추출물에 적어도 하나 이상의 부형제 예를 들면, 전분, 칼슘카보네이트(calcium carbonate), 수크로스(sucrose) 또는 락토오스(lactose), 젤라틴 등을 섞어 조제된다. 또한 단순한 부형제 이외에 마그네슘 스티레이트 탈크 같은 윤활제들도 사용된다. 경구를 위한 액상제제로는 현탁제, 내용액제, 유제, 시럽제 등이 해당되는데 흔히 사용되는 단순희석제인 물, 리퀴드 파라핀 이외에 여러 가지 부형제, 예를 들면 습윤제, 감미제, 방향제, 보존제 등이 포함될 수 있다. 비경구 투여를 위한 제제에는 멸균된 수용액, 비수성용제, 현탁제, 유제, 동결건조제제, 좌제가 포함된다. 비수성용제, 현탁제로는 프로필렌글리콜 (propylene glycol), 폴리에틸렌 글리콜, 올리브 오일과 같은 식물성 기름, 에틸올레이트와 같은 주사 가능한 에스테르 등이 사용될 수 있다. 좌제의 기제로는 위텝솔(witepsol), 마크로골, 트윈(tween) 61, 카카오지, 라우린지, 글리세로제라틴 등이 사용될 수 있다.The 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. When formulated, diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrating agents, and surfactants are usually used. 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. In addition to simple excipients, 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. As 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.
다른 하나의 양태로서, 본 발명은 산조인 추출물 및 양유근 추출물을 포함하는 인지기능장애 또는 퇴행성 뇌질환의 예방 또는 개선용 건강기능식품 조성물 또는 식품 조성물을 제공한다. As another aspect, 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.
상기 산조인, 산조인 추출물, 양유근, 양유근 추출물, 인지기능장애, 퇴행성 뇌질환은 앞서 설명한 바와 같다. The Sanjoin, Sanjoin Extract, Yang Yu-geun, Yang Yu-geun Extract, cognitive dysfunction, degenerative brain disease are as described above.
바람직하게, 본 발명에 따른 건강기능식품 조성물 중 산조인 추출물은 Zizypus jujuba var. spinosa의 에탄올 또는 수 추출물일 수 있고, 양유근 추출물은 Codonopsis lanceloata의 에탄올 또는 수 추출물일 수 있다. Preferably, 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 .
바람직하게, 본 발명에 따른 건강기능식품 조성물 중 산조인 추출물 및 양유근 추출물은 전체 조성물 중에 1:1 내지 10:1, 보다 바람직하게 1:1 내지 6:1, 특히 바람직하게 5:1의 중량비로 포함될 수 있다. Preferably, 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.
본 발명에서, 개선이란 증상의 치료, 경감, 예방을 포함하는 의미로서, 본 발명에서는 인지기능장애 및 퇴행성 뇌질환, 예를 들어 뇌졸중, 중풍, 건망증, 치매, 알츠하이머 질환, 파킨슨 질환 또는 헌팅턴 질환이 치료, 경감 또는 예방되는 것을 말한다. In the present invention, 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.
본 발명의 산조인 추출물 및 양유근 추출물을 포함하는 건강기능식품 조성물 또는 식품 조성물에서 산조인 추출물 및 양유근 추출물은 인지기능장애 또는 퇴행성 뇌질환의 개선 효과를 나타낼 수 있는 한 용도, 제형, 배합 목적에 따라 임의의 양(유효량)으로 포함할 수 있다. 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).
본 발명에서 유효량이란 인지기능장애 또는 퇴행성 뇌질환의 개선 효과를 유도할 수 있는 유효성분의 양을 말한다. 이러한 유효량은 당업자의 통상의 능력 범위 내에서 실험적으로 결정될 수 있다.In the present invention, 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.
본 발명의 건강기능식품 조성물 또는 식품 조성물은 여러 가지 영양제, 비타민, 광물(전해질), 합성 풍미제 및 천연 풍미제 등의 풍미제, 착색제 및 중진제(치즈, 초콜릿 등), 펙트산 및 그의 염, 알긴산 및 그의 염, 유기산, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알코올, 탄산음료에 사용되는 탄산화제 등을 함유할 수 있다. 그 밖에 천연 과일쥬스 및 과일 쥬스 음료 및 야채 음료의 제조를 위한 과육을 함유할 수 있다. 이러한 성분은 독립적으로 또는 조합하여 사용할 수 있다. 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.
또한 본 발명의 건강기능식품 조성물 또는 식품 조성물은 식품 또는 음료의 다양한 형태, 예를 들어 육류, 소세지, 빵, 쵸코렛, 캔디류, 스넥류, 과자류, 피자, 라면, 껌류, 아이스크림류, 스프, 음료수, 차, 기능수, 드링크제, 알콜 음료 및 비타민 복합제 중 어느 하나의 형태일 수 있으며, 분말, 과립, 정제, 캡슐, 또는 액제 등의 형태로 사용될 수 있다. In addition, the 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.
본 발명의 산조인 및 양유근 복합추출물은 인지기능장애 또는 퇴행성 뇌질환 관련 질환의 예방 및 개선을 목적으로 식품 또는 음료에 첨가될 수 있다. 이 때, 식품 또는 음료 중의 상기 복합추출물의 양은 통상 전체 식품 조성물 중량의 1 내지 5 중량%로 가할 수 있으며, 음료 조성물은 100 ㎖를 기준으로 0.02 내지 10 g, 바람직하게는 0.3 내지 1 g의 비율로 가할 수 있다. 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. At this time, 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.
또한, 상기 음료 조성물은 지시된 비율로 필수 성분으로서 상기 복합추출물을 함유하는 것 외에 액체성분으로 특별한 제한점은 없으며 통상의 음료로서 여러 가지 향미제 또는 천연 탄수화물 등을 추가 성분으로서 함유할 수 있다. 천연 탄수화물의 예는 모노사카라이드, 예를 들어, 포도당, 과당 등의 디사카라이드, 예를 들어 말토스, 슈크로스 등의 폴리사카라이드, 예를 들어 덱스트린, 시클로덱스트린 등과 같은 통상적인 당 및 자일리톨, 소르비톨, 에리트리톨 등의 당알콜을 들 수 있다. 기타 향미제로서 천연 향미제(타우마틴, 스테비아 추출물(예를 들어 레바우디오시드 A, 글리시르히진 등) 및 합성 향미제(사카린, 아스파르탐 등)를 필요에 따라 유리하게 사용할 수 있다. 상기 천연 탄수화물의 비율은 본 발명의 조성물 100 mL당 일반적으로 약 1 내지 20 g, 바람직하게는 약 5 내지 12 g이다.In addition, 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. Examples of 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. As other flavors, natural flavors (tauumatin, stevia extracts (e.g. rebaudioside A, glycyrrhizin, etc.) and synthetic flavors (saccharin, aspartame, etc.) can be advantageously used as necessary. 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.
또한 상기 건강기능식품 조성물은 식품첨가물을 추가로 포함할 수 있으며, 식품첨가물로서의 적합여부는 다른 규정이 없는 한 식품의약품안전처에 승인된 식품첨가물공전의 총칙 및 일반시험법 등에 따라 해당 품목에 관한 규격 및 기준에 의하여 판정한다. In addition, 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.
상기 "식품첨가물공전"에 수재된 품목으로 예를 들어, 케톤류, 글리신, 구연산칼륨, 니코틴산, 계피산 등의 화학적 합성품, 감색소, 감초추출물, 결정셀롤로오스, 구아검 등의 천연첨가물, L-글루타민산나트륨제제, 면류첨가알칼리제, 보존료제제, 타르색소제제 등의 혼합 제제류들을 들 수 있다.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.
상기 건강기능식품을 제조하는 과정에서 음료를 포함한 식품에 첨가되는 본 발명에 따른 복합 추출물은 필요에 따라 그 함량을 적절히 가감할 수 있다. 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.
또한, 본 발명은 인지기능장애 또는 퇴행성 뇌질환의 예방, 개선 또는 치료를 필요로 하는 대상체에게 상술한 본 발명의 약학적 조성물 또는 식품 조성물을 투여하는 것을 포함하는, 인지기능장애 또는 퇴행성 뇌질환의 예방, 개선 또는 치료 방법을 제공한다. 본 발명에 있어서, 상기 대상체는 포유류, 특히 인간을 포함한다. In addition, 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. In the present invention, the subject comprises a mammal, in particular a human.
또한, 본 발명은 인지기능 장애 또는 퇴행성 뇌질환의 예방, 개선 또는 치료를 위한 약제 또는 식품의 제조를 위한, 상술한 본 발명의 약학적 조성물 또는 식품 조성물의 용도를 제공한다.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.
상기 인지기능장애 또는 퇴행성 뇌질환은 본 명세서에서 상술한 것과 동일하다.The cognitive dysfunction or degenerative brain disease is the same as described above in the present specification.
본 발명의 산조인 추출물 및 양유근 추출물의 복합 추출물을 포함하는 조성물은 학습 및 기억력을 현저하게 개선시켜, 인지기능장애 또는 퇴행성 뇌질환을 효과적으로 예방, 치료 및 개선할 수 있다. The 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.
도 1은 산조인 50% 에탄올 추출물을 스코폴라민으로 유도한 기억력 감퇴 동물에게 농도 의존적(50, 100, 200 및 400 mg/kg)으로 투여하고 수동회피 실험에서 어두운 방으로 들어가는 시간을 측정한 결과를 나타낸 그래프이다. 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.
도 2는 양유근 50% 에탄올 추출물을 스코폴라민으로 유도한 기억력 감퇴 동물에게 농도 의존적(25, 50, 100 및 200 mg/kg)으로 투여하고 수동회피 실험에서 어두운 방으로 들어가는 시간을 측정한 결과를 나타낸 그래프이다. 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.
도 3은 산조인 및 양유근 단일 추출물과 산조인과 양유근의 복합추출물의 스코폴라민으로 유도한 기억력 감퇴 동물에서의 기억력 감퇴에 대한 개선효과를 비교한 것으로 동일 농도(100 mg/kg)로 투여했을 때 수동회피 실험에서 어두운 방으로 들어가는 시간을 측정한 결과를 나타낸 그래프이다. 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.
도 4는 산조인 및 양유근의 5:1 중량비 복합추출물을 스코폴라민으로 유도한 기억력 감퇴 동물에 농도 의존적(50, 100, 200 및 400 mg/kg)으로 투여하고 수동회피 실험에서 어두운 방으로 들어가는 시간을 측정한 결과를 나타낸 그래프이다. 4 is a time-dependent dose (50, 100, 200 and 400 mg / kg) administered to the scopolamine-induced memory deprived animals of the 5: 1 weight ratio complex extracts of Sanjoin and Yang Yu-geun and enter the dark room in the passive avoidance experiment. Is a graph showing the results of the measurement.
도 5는 산조인 및 양유근의 5:1 중량비 복합추출물을 스코폴라민으로 유도한 기억력 감퇴 동물에 농도 의존적(50, 100, 200 및 400 mg/kg)으로 투여하고 Y-미로 실험에서 변경 행동력 및 총 출입수을 측정한 결과를 나타낸 그래프이다. 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.
도 6은 산조인 및 양유근 5:1 중량비 복합추출물을 스코폴라민으로 유도한 기억력 감퇴 동물에 100, 200 및 400 mg/kg으로 투여하고 모리스 수중 미로 실험의 훈련실험에서 플랫폼을 찾는 시간을 측정한 결과를 나타낸 그래프이다. 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.
도 7은 산조인 및 양유근 5:1 중량비 복합추출물을 베타 아밀로이드 단백질로 유도한 기억력 감퇴 동물에게 농도 의존적(100, 200 및 400 mg/kg)으로 투여하고 수동회피 실험에서 어두운 방으로 들어가는 시간을 측정한 결과를 나타낸 그래프이다.7 is a concentration-dependent (100, 200 and 400 mg / kg) administered to the memory loss animals induced by beta amyloid protein with Sanjoin and Yang Yu-geun 5: 1 weight ratio complex extract and measured the time to enter the dark room in the passive avoidance experiment A graph showing the results.
도 8은 산조인 및 양유근 5:1 중량비 복합추출물을 스코폴라민으로 유도한 기억력 감퇴 동물에 농도 의존적(50, 100, 200 및 400 mg/kg)으로 투여하고 Y-미로 실험에서 변경 행동력 및 총 출입수을 측정한 결과를 나타낸 그래프이다.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.
이하, 본 발명의 이해를 돕기 위하여 바람직한 실시예를 제시한다. 그러나, 하기의 실시예는 본 발명을 더욱 쉽게 이해하기 위하여 제공되는 것일 뿐, 실시예에 의하여 본 발명의 내용이 한정되는 것은 아니다. Hereinafter, preferred examples are provided to aid in understanding the present invention. However, the following examples are merely provided to more easily understand the present invention, and the contents of the present invention are not limited by the examples.
재료: 약물 및 시약Ingredients: Drugs and Reagents
스코폴라민(scopolamine) 및 도네페질(donepezil)은 Sigma-Aldrich Chemistry Co.에서 구입하여 사용하였으며, 베타 아밀로이드는 American Peptide Co.에서 구입하였고, 그 외 시약은 시중에서 구입할 수 있는 최상급을 사용하였다.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.
실시예: 산조인과 양유근의 복합추출물 제조Example: Preparation of Complex Extract of Sanjoin and Yang Yu-geun
산조인(Zizyphus jujuba Mill var. spinosa Hu의 씨) 또는 양유근( Codonopsis lanceolata의 뿌리)을 중량비 1:1에서 6:1의 비율로 각각 칭량하였다. 그리고 칭량한 산조인과 양유근을 분쇄기로 분쇄하여 혼합한 후 총 중량의 5배수에 해당하는 50% 에탄올을 가하여 75~80℃에서 3시간 환류 추출하였으며, 잔사에 중량대비 4배수의 에탄올을 가하여 75~80℃에서 3시간 동안 환류 추출 후 여과시켰다. 그 후, 추출액을 모두 합하여 감압 농축 후 건조과정을 거쳐 산조인과 양유근의 복합추출물을 제조하였다.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.
참고예Reference Example 1: 산조인 및  1: Sanjoin and 양유근Yoo Keun Yang 단일 추출물의 제조  Preparation of Single Extract
산조인(Zizyphus jujuba Mill var. spinosa Hu의 씨) 또는 양유근( Codonopsis lanceolata의 뿌리)을 100 g 중량으로 각각 칭량하였다. 그리고 칭량한 산조인 또는 양유근을 분쇄기로 분쇄하여 혼합한 후 총 중량의 5배수에 해당하는 50% 에탄올을 가하여 75~80℃에서 3시간 환류 추출하였으며, 잔사에 중량대비 4배수의 에탄올을 가하여 75~80℃에서 3시간 동안 환류 추출 후 여과시켰다. 그 후, 추출액을 모두 합하여 감압 농축 후 건조과정을 거쳐 산조인 및 양유근의 단일 추출물을 제조하였다.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.
참고예Reference Example 2: 실험동물의 준비  2: Preparation of Laboratory Animals
6주령의 ICR 마우스(26 - 28 g) 를 (주) 오리엔트(Seoul, Korea)에서 공급받아 경희대학교 약학대학의 동물 실험실에 약 5일간 적응시켜 사용하였으며, 물과 사료는 자유롭게 섭취하도록 하였고, 온도(23 ± 2 ℃), 습도(50 ± 10 %) 및 명암주기(12 시간)는 자동으로 조절되도록 하였다. 이하, 실험에서는 각 약물투여군 및 대조군 당 준비된 마우스 10마리씩을 사용하여 실험하였다.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. Hereinafter, the experiment was conducted using 10 mice prepared for each drug administration group and control group.
참고예Reference Example 3: 통계처리 3: Statistical processing
모든 실험 결과는 ANOVA (one way analysis of variance)를 이용하여 통계 처리하였고, 유의성이 인정될 경우 Student-Newman-Keuls Test를 사용하여 p < 0.05 수준 이하에서 유의성 검정을 실시하였다.All experimental results were statistically analyzed using ANOVA (one way analysis of variance), and the significance test was performed at p <0.05 level using Student-Newman-Keuls Test when significance was recognized.
실험예Experimental Example 1. 스코폴라민에 의해 유도된 건망증 모델을 이용한 산조인 또는  1. Sanjoin using a forgetful model induced by scopolamine or 양유근의Yogeuneun 단일 추출물과 산조인 및  Single extracts and acid joins and 양유근Yoo Keun Yang 복합추출물의 수동회피 실험 Manual Evasion Experiment of Complex Extracts
(1) 실험 방법(1) Experiment Method
약물투여군으로 참고예 1에서 제조한 산조인 추출물 및 양유근 추출물과, 실시예에서 제조한 산조인 및 양유근의 복합추출물(산조인:양유근 1:1, 2:1, 3:1, 4:1, 5:1 및 6:1의 중량비)을 0.5% CMC (carboxymethylcellulose: Sigma, U.S.A.)에 녹인 후 참고예 2의 마우스에 경구 투여하였다. 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.
대조군 1은 도네페질 5 mg/kg을 투여한 군이고, 대조군 2는 약물 미투여군이며, 대조군 3은 10% CMC만을 투여한 군이다. 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.
상기 약물 투여 30분 후에 약물투여군, 대조군 1 및 2에 0.9% 생리식염수에 녹인 스코폴라민을 1 mg/kg의 용량으로 복강 투여하였다(Ebert, U. et al., Eur. J. Clin. Invest., 28, pp944-949, 1998). 스코폴라민 투여 30분 후에 마우스를 조명을 비춘 밝은 쪽 구획에 놓고 10초의 탐색시간 후 길로틴문(guillotin door)이 열려 어두운 구획으로 들어갈 수 있게 하였다. 이때 길로틴문이 열린 후 60초 이내에 어두운 쪽으로 들어가지 않는 마우스는 실험에서 제외시켰다. 길로틴문이 열린 후 마우스가 어두운 쪽으로 들어갈 때까지의 시간을 측정하였다. 일단 마우스가 어두운 쪽으로 들어가면 길로틴문이 닫히고 0.5 mA의 전기 충격이 3초 동안 격자 바닥을 통해 흐르게 되고 마우스는 이러한 전기작용을 기억하게 된다.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). Thirty minutes after scopolamine administration, 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.
학습 시험이 끝나고 24시간 후에 본 실험을 시행하였다. 마우스가 10초의 탐색시간 후 길로틴문이 열리고 어두운 쪽으로 네 발이 다 들어가는데 걸리는 시간(latency time : 머무름 시간)을 300초까지 측정하였다. 걸리는 시간이 길수록 수동회피의 학습과 기억이 좋음을 나타낸다.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.
(2) 실험 결과(2) experimental results
약물 및 스코폴라민을 전혀 처리하지 않은 대조군 3에 비해 스코폴라민만 투여한 대조군 2의 머무름 시간이 유의성 있게 감소한 것으로 보아 기억력 감퇴 모델이 제작되었음을 확인하였다. 참고예 1에 따른 산조인 단일 에탄올 추출물의 수동회피실험 결과는 표 1 및 도 1에 나타내었고, 참고예 1에 따른 양유근 단일 에탄올 추출물의 수동회피실험 결과는 표 2 및 도 2에 나타내었고, 참고예 1과 실시예에 따른 산조인 및 양유근 단일 추출물과, 산조인 및 양유근 복합추출물의 수동회피실험 결과는 표 3 및 도 3에 나타내었으며, 실시예에 따른 산조인 및 양유근 5:1 중량비 복합추출물의 용량의존성 수동회피실험 결과는 표 4 및 도 4에 나타내었다.It was confirmed that the memory loss model was produced because the retention time of the scopolamine-only control 2 was significantly reduced compared to the control 3 without the drug and the scopolamine at all. Passive avoidance test results of the single ethanol extract of the acid tank according to the reference example 1 are shown in Table 1 and Figure 1, the results of the passive avoidance test of yangeungeun single ethanol extract according to Reference Example 1 are shown in Table 2 and Figure 2, Reference Example The results of passive avoidance experiments of single extract of Sanjoin and Yang-Yu-Keun and Sanjoin and Yang-Yu-Keun complex extracts according to Example 1 and Example are shown in Table 3 and FIG. 3, and dose-dependent manual of Sanjoin and Yang-Yu-Keun 5: 1 weight ratio complex extracts according to the Examples. The avoidance test results are shown in Table 4 and FIG. 4.
표 1 및 도 1에서 확인할 수 있는 바와 같이 산조인 단일 에탄올 추출물에 대한 용량의존성 실험에서 스코폴라민만 투여한 군(대조군 2)의 머무름 시간이 59.10 ± 24.45 초인데 반해 산조인 단일 에탄올 추출물의 100 mg/kg 투여군(약물투여군 2)에서 134.2 ± 23.80 (p < 0.05) 초, 200 mg/kg 투여군(약물투여군 3)에서 157.8 ± 56.78 (p < 0.05), 400 mg/kg 투여군(약물투여군 4)에서 176.5 ± 48.21 초로 유의성 있는 증가를 보였다.As shown in Table 1 and FIG. 1, the retention time of the scopolamine-only group (control 2) 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.
Figure PCTKR2016010336-appb-T000001
Figure PCTKR2016010336-appb-T000001
표 2 및 도 2에서 확인할 수 있는 바와 같이 양유근 단일 에탄올 추출물에 대한 용량의존성 실험에서 스코폴라민만 투여한 군(대조군 2)의 머무름 시간이 22.41 ± 18.93 초인데 반해 양유근 단일 에탄올 추출물의 50 mg/kg 투여군(약물투여군 2)에서 142.3 ± 26.63 (p < 0.05) 초, 100 mg/kg 투여군(약물투여군 3)에서 119.5 ± 22.39 (p < 0.05)초로 유의성 있는 증가를 보였다.As shown in Table 2 and FIG. 2, the retention time of the scopolamine-only group (control 2) was 22.41 ± 18.93 seconds in the dose-dependence experiment on the yang-geun single ethanol extract 50 mg / There was a significant increase of 142.3 ± 26.63 ( p <0.05) seconds in the kg administration group (drug group 2) and 119.5 ± 22.39 ( p <0.05) seconds in the 100 mg / kg group (drug group 3).
Figure PCTKR2016010336-appb-T000002
Figure PCTKR2016010336-appb-T000002
표 3 및 도 3에는 산조인 및 양유근의 단일 추출물과 다양한 조성비로 배합한 산조인과 양유근의 복합추출물 100 mg/kg에 대한 기억력 개선 효능 결과를 나타내었다. 스코폴라민만 투여한 군(대조군 2)의 머무름 시간이 43.40 ± 30.04 초인데 반해 산조인 단일 추출물을 투여한 군(약물투여군 1)의 머무름 시간은 174.8 ± 63.78 (p < 0.05) 초, 양유근 단일 에탄올 추출물을 투여한 군(약물투여군 2)의 머무름 시간이 129.4 ± 37.31 (p < 0.05) 초였다. 산조인과 양유근의 복합추출물은 산조인과 양유근이 3:1 중량 조성비일 때(약물투여군 5) 159.8 ± 77.52 (p < 0.05) 초, 산조인과 양유근이 4:1 중량 조성비일 때(약물투여군 6) 174.8 ± 75.54 (p < 0.05) 초, 산조인과 양유근이 5:1 중량 조성비일 때(약물투여군 7) 221.9 ± 44.62 (p < 0.05) 초, 산조인과 양유근이 6:1 중량 조성비일 때(약물투여군 8) 182.4 ± 60.79 (p < 0.05) 초로 산조인과 양유근이 5:1 중량 조성비일 때(약물투여군 7) 가장 우수한 학습 및 기억력 개선효과가 있음을 확인하였다. 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, whereas 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 (drug group 2) 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.
Figure PCTKR2016010336-appb-T000003
Figure PCTKR2016010336-appb-T000003
표 4 및 도 4에서 확인할 수 있는 바와 같이, 산조인과 양유근의 5:1 중량비 복합추출물에 대한 용량의존성 실험에서 스코폴라민만 투여한 군(대조군 2)의 머무름 시간이 52.89 ± 12.77 초인데 반해 산조인과 양유근의 5:1 중량비 복합추출물의 100 mg/kg 투여군(약물투여군 2)에서 142.0 ± 37.50 (p < 0.05) 초, 200 mg/kg 투여군(약물투여군 3)에서 176.7 ± 66.66 (p < 0.05)초, 400 mg/kg 투여군(약물투여군 4)에서 180.1 ± 66.96 (p < 0.05) 초로 유의성 있는 증가를 보였다.As can be seen in Table 4 and FIG. 4, 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) Second, in the 400 mg / kg group (drug group 4), there was a significant increase of 180.1 ± 66.96 ( p <0.05) seconds.
Figure PCTKR2016010336-appb-T000004
Figure PCTKR2016010336-appb-T000004
실험예Experimental Example 2. 스코폴라민에 의해 유도된 건망증 모델을 이용한 Y-미로 실험 2. Y-maze experiments using scopolamine-induced forgetfulness model
실험예 1과 같은 방법으로 제조한 스코폴라민(1 mg/kg, i.p)을 투여한 기억력 감퇴 동물모델을 이용하여 산조인과 양유근의 5:1 중량비 복합추출물이 기억력 손상을 억제하여 주는 효과가 있는지의 여부를 Y-미로 실험장치를 이용하여 하기와 같이 실험하였다. Y-미로시험에 이용되는 기구는 3개의 가지로 구성되어 있으며, 각 가지(arm)의 길이는 42 cm, 넓이는 3 cm, 높이는 12 cm이고 세 팔이 접하는 각도는 120°였다. 모든 실험 장치는 검정색의 폴리비닐 플라스틱(polyvinyl plastic)으로 장치하였다.Using a memory-depleted animal model administered with scopolamine (1 mg / kg, ip) prepared in the same manner as Experimental Example 1, was there an effect of inhibiting memory impairment by the 5: 1 weight ratio complex extract of Sanjoin and Yang Yu-geun? Whether or not using the Y-maze experiment was tested as follows. The instrument used for the Y-maze test consisted of three branches, each arm was 42 cm long, 3 cm wide, 12 cm high and the angle of contact between the arms was 120 °. All experimental devices were equipped with black polyvinyl plastic.
실시예에 따른 산조인과 양유근의 5:1 중량비 복합추출물을 0.5%의 CMC (carboxymethylcellulose, Sigma, U.S.A.) 4 ml에 녹인 후 50, 100, 200 및 400 mg/kg 으로 참고예 2의 마우스에 경구 투여하였다. 양성 대조군(대조군 1)은 도네페질(donepezil) 5 mg/kg을 투여하고, 대조군 2는 약물 미투여군이며, 음성 대조군(대조군 3)에는 0.5% CMC만을 투여하였다.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.
상기 약물투여 30분 후에 증류수 5 ml에 스코폴라민 1 mg을 녹여 이를 1 mg/kg의 용량으로 약물투여군, 대조군 1 및 2의 마우스에 복강 투여하고, 스코폴라민 투여 30분 후에 각 가지를 A, B, C로 정한 후, 한쪽 가지에 마우스를 조심스럽게 놓고 8분 동안 자유롭게 움직이게 한 다음, 마우스가 들어간 가지를 기록하였다. 이 때 꼬리까지 완전히 들어갔을 경우에 한하며, 갔던 가지에 다시 들어간 경우에도 기록하였다. 세 개의 다른 가지에 차례로 들어간 경우 1점(실제 변경, actual alternation)씩 부여하였다. 변경 행동력(alternation behavior)은 3가지 모두에 차례로 들어가는 것으로 정의되며, 하기 수학식 1에 의해 계산하였다(Sarter, M. et al., Psychopharmacology., 94, pp491-495, 1998).Thirty minutes after the drug administration, 1 mg of scopolamine was dissolved in 5 ml of distilled water, and it was intraperitoneally administered to the mice of the drug administration group, the control groups 1 and 2 at a dose of 1 mg / kg, and 30 minutes after the scopolamine administration, each branch was A. After setting as B, C, the mouse was carefully placed on one branch and allowed to move freely for 8 minutes, and then the branch containing the mouse was recorded. Only when the tail is completely entered, it is also recorded when the branch went back. One point (actual alteration) was given to three different branches in turn. Alteration behavior is defined as entering all three in turn, and was calculated by Equation 1 below (Sarter, M. et al., Psychopharmacology., 94, pp 491-495, 1998).
Figure PCTKR2016010336-appb-M000001
Figure PCTKR2016010336-appb-M000001
(최고변경 : 총 입장횟수 - 2)(Maximum change: Total number of admissions-2)
그 결과, 표 5 및 도 5와 같이 스코폴라민(1 mg/kg, i.p)의 투여에 의해 변경 행동력(spontaneous alternation)이 대조군 3에 비해 통계적으로 유의성 있게 감소하였다(*, P < 0.05 vs. 대조군, 도 5A 및 표 5 참조). 이러한 감소는 변경 행동력(spontaneous alternation)이 산조인과 양유근의 5:1 중량비 복합추출물의 투여에 의해 증가하였으며, 거의 정상상태의 변경 행동(spontaneous alternation) 수준으로 회복되는 것을 확인할 수 있었다(#, P < 0.05 vs. 스코폴라민 투여군). 변경 행동력(Spontaneous alternation)이 증가한다는 것은 학습 및 기억력이 회복되었다는 것을 의미하는 반면, 각 구역으로 들어가는 총 횟수를 나타내는 총출입수(total entry)에는 변화가 없는 것으로 나타나 변경 행동력(spontaneous alternation)이 마우스의 활동성 변화에 의해 나타난 것이 아님을 알 수 있었다.As a result, as shown in Table 5 and Figure 5, the administration of scopolamine (1 mg / kg, ip) significantly reduced the spontaneous alternation compared to the control 3 (*, P <0.05 vs. Control, see FIG. 5A and Table 5. This decrease was increased by the administration of the 5: 1 weight ratio complex extract of Sanjoin and Yang Yu-geun, and the recovery of almost normal steady-state alteration was found (#, P < 0.05 vs. scopolamine administration group). Increased spontaneous alternation means that learning and memory have been restored, while there has been no change in the total entry, which indicates the total number of entries into each zone. It was found that it was not caused by the change in activity.
Figure PCTKR2016010336-appb-T000005
Figure PCTKR2016010336-appb-T000005
실험예Experimental Example 3. 스코폴라민에 의해 유도된 건망증 모델을 이용한 모리스 수중 미로 실험 3. Morris's Maze Experiment Using Skopolamine-Induced Forgetfulness Model
(1) 실험 방법(1) Experiment Method
실시예에 따른 산조인과 양유근의 5:1 중량비 복합추출물을 0.5% CMC에 녹인 후 100, 200 및 400 mg/kg의 용량으로 참고예 2의 마우스에 경구 투여하였다. 양성 대조군(대조군 1)은 도네페질 5 mg/kg을 투여하고, 대조군 2는 약물 미투여군이며, 음성 대조군(대조군 3)에는 0.5% CMC을 투여하였다.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.
상기 약물투여 30분 후에 증류수 5 ml에 스코폴라민 1 mg을 녹여 이를 1 mg/kg의 용량으로 약물투여군 및 대조군 1 및 2의 마우스에 복강 투여하였다. Thirty minutes after the drug administration, 1 mg of scopolamine was dissolved in 5 ml of distilled water, which was intraperitoneally administered to the mice of the drug administration group and the control groups 1 and 2 at a dose of 1 mg / kg.
지름 90 cm, 높이 45 cm인 원형 풀에 각각 별, 네모, 세모, 원의 네 가지 표지를 같은 간격으로 붙이고 이 중 별 아래에 29 cm 높이의 플랫폼 (platform)을 위치시켰다. 플랫폼 보다 0.5 cm 윗부분까지 물을 채우고(수온 21 ± 1 ℃), 색소를 이용하여 물을 흐리게 하여 수면에서 플랫폼이 보이지 않게 하였다. 마우스를 풀의 한 구획에 조심스럽게 내려놓은 다음 플랫폼까지 찾아가는 시간을 60초 동안 측정하였다. 30초 후 다시 같은 위치에 마우스를 내려놓고 플랫폼까지 찾아가는 시간을 60초 동안 측정하였다. 위의 과정을 4번 반복하고, 총 4일 동안 내려놓는 위치를 바꿔가며 실시하였다.Four covers of stars, squares, triangles, and circles were equally spaced on a circular grass 90 cm in diameter and 45 cm high, and a 29 cm high platform was placed below the star. Water was filled up to 0.5 cm above the platform (water temperature 21 ± 1 ° C.) and the water was clouded with pigments to make the platform invisible at the water surface. The mouse was carefully lowered into one compartment of the pool and the time to reach the platform was measured for 60 seconds. After 30 seconds, the mouse was placed in the same position again and the time to reach the platform was measured for 60 seconds. The above process was repeated four times, changing the position of laying down for a total of four days.
(2) 실험 결과(2) experimental results
그 결과, 모든 실험에서 대조군 3에 비해 스코폴라민만 투여한 대조군 2의 플랫폼까지 걸린 시간의 감소가 유의성이 없었던 것으로 보아 기억력 감퇴 모델이 제작되었음을 알 수 있었다. 도 6에서 확인할 수 있듯이, 훈련실험에서 스코폴라민만 투여한 대조군 2의 플랫폼까지 걸린 시간이 3일과 4일차에 각각 53.25 ± 11.14초, 51.60 ± 14.42초인데 반해 산조인과 양유근의 5:1 중량비 복합추출물 100 mg/kg 투여군에서는 35.00 ± 8.134 (p <0.05) 초, 34.65 ± 9.773 (p <0.05) 초, 200 mg/kg 투여군에서는 32.15 ± 14.16 (p <0.05) 초, 30.15 ± 13.18(p <0.05) 초, 400 mg/kg 투여군에서는 31.00 ± 13.09 (p <0.05) 초, 27.80 ± 11.04 (p <0.05) 초로 유의성 있는 감소를 보였다(표 6 및 도 6A). 훈련 후 플랫폼을 제거하고 마우스가 플랫폼이 있던 사분면에 머무르는 시간을 측정하였을 때 스코폴라민만 투여한 대조군 2의 머무름 시간이 15.75 ± 2.886초인데 반해 산조인과 양유근의 5:1 중량비 복합추출물 100 mg/kg 투여군에서는 22.21 ± 3.774 (p <0.05) 초, 200 mg/kg 투여군에서는 22.51 ± 3.723(p <0.05) 초, 400 mg/kg 투여군에서는 22.02 ± 2.733 (p <0.05) 초로 유의성 있는 증가를 보였다(표 7 및 도 6B).As a result, there was no significant reduction in the time taken to the platform of the control group 2 administered scopolamine only in all experiments compared to the control group 3 It can be seen that the memory loss model was produced. As can be seen in Figure 6, the time taken to the platform of the control group 2 administered scopolamine only in the training experiment was 53.25 ± 11.14 seconds, 51.60 ± 14.42 seconds on the 3rd and 4th day, respectively, 5: 1 weight ratio of Sanjoin and Yang Yugeun Extract 35.00 ± 8.134 (p <0.05) seconds in the 100 mg / kg group, 34.65 ± 9.773 (p <0.05) seconds, 32.15 ± 14.16 (p <0.05) seconds in the 200 mg / kg group, 30.15 ± 13.18 (p <0.05) ), 400 mg / kg administration group showed a significant decrease of 31.00 ± 13.09 (p <0.05) seconds, 27.80 ± 11.04 (p <0.05) seconds (Table 6 and Figure 6A). When the platform was removed after training and the mouse stayed in the quadrant where the platform was located, the retention time of the control group 2 administered with scopolamine was 15.75 ± 2.886 seconds, whereas the 5: 1 weight ratio complex extract of Sanjoin and Yang Yugeun was 100 mg / There was a significant increase of 22.21 ± 3.774 (p <0.05) seconds in the kg group, 22.51 ± 3.723 (p <0.05) seconds in the 200 mg / kg group, and 22.02 ± 2.733 (p <0.05) seconds in the 400 mg / kg group ( Table 7 and FIG. 6B).
Figure PCTKR2016010336-appb-T000006
Figure PCTKR2016010336-appb-T000006
Figure PCTKR2016010336-appb-T000007
Figure PCTKR2016010336-appb-T000007
실험예Experimental Example 4. 베타 아밀로이드 단백질에 의해 유도된 치매 모델을 이용한  4. Using a dementia model induced by beta amyloid protein 산조인과Sanjoin Family 양유근Yoo Keun Yang 5:1 중량비 복합추출물의 수동회피 실험 Manual Evasion Experiment of 5: 1 Weight Ratio Complex Extracts
(1) 베타 아밀로이드 단백질 유도 치매 마우스의 제작(1) Fabrication of Beta Amyloid Protein-induced Dementia Mice
베타 아밀로이드 단백질 1-42 fragment (American peptide, USA)를 구입하여 0.9% 생리식염수에 1 mg/ml의 농도로 용해하였다. 그 후 37 ℃에서 24시간 동안 베타 아밀로이드 단백질을 응집시킨 후 사용하였다. 참고예 2의 마우스를 2% 아이소플루레인(isofluorane)으로 흡입마취를 유도한 후, 우측 뇌실에 3 μ를 해밀턴 실린지를 이용하여 투여하였다. 음성 대조군에는 0.9% 생리식염수를 투여하였다. 베타 아밀로이드 투여 직후 약물을 경구투여하였으며, 약물을 동량으로 1일 1회 총 7일간 투여하였다.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 ℃ for 24 hours. After inducing anesthesia with 2% isofluorane in mice of Reference Example 2, 3 μ 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.
(2) 실험 방법(2) Experiment method
실시예에 따른 산조인과 양유근 5:1 중량비 복합추출물을 0.5% CMC에 녹인 후 여러 가지 용량(100, 200 및 400 mg/kg)으로 실험예 4-(1)의 마우스에 7일간 경구 투여하였다. 양성 대조군(대조군 1)은 도네페질(donepezil) 5 mg/kg을 7일간 경구투여하고, 음성 대조군(대조군 3)에는 0.5% CMC를 7일간 경구투여하였다. 단회투여에 의한 효과를 피하기 위해 마지막 약물 투여 24시간 후에 마우스를 조명을 비춘 밝은 쪽 구획에 놓고 20초의 탐색시간 후 길로틴문(guillotin door)이 열려 어두운 구획으로 들어갈 수 있게 하였다. 이때 길로틴문이 열린 후 60초 이내에 어두운 쪽으로 들어가지 않는 마우스는 실험에서 제외시켰다. 길로틴문이 열린 후 마우스가 어두운 쪽으로 들어갈 때까지의 시간을 측정하였다. 일단 마우스가 어두운 쪽으로 들어가면 길로틴문이 닫히고 0.5 mA의 전기 충격이 3초 동안 격자 바닥을 통해 흐르게 되고 마우스는 이러한 전기작용을 기억하게 된다.Sanjoin and Yang Yu-geun 5: 1 weight ratio composite extract according to the example was dissolved in 0.5% CMC and then administered orally to the mice of Experimental Example 4- (1) at various doses (100, 200 and 400 mg / kg) for 7 days. 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. To avoid the effect of a single dose, the mice were placed in the illuminated bright compartment 24 hours after the last drug administration and the guillotine door was opened to enter the dark compartment after 20 seconds of exploration. 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.
학습 시험이 끝나고 24시간 후에 본 실험을 시행하였다. 마우스가 10초의 탐색시간 후 길로틴문이 열리고 어두운 쪽으로 4발이 다 들어가는데 걸리는 시간(latency time : 머무름 시간)을 300초까지 측정하였다. 걸리는 시간이 길수록 수동회피의 학습과 기억이 좋음을 나타낸다.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.
(3) 실험 결과(3) experimental results
그 결과, 표 8 및 도 7에서 확인할 수 있듯이 대조군 3에 비해 베타 아밀로이드 단백질만 투여한 군(대조군 2)의 머무름 시간이 유의성 있게 감소한 것으로 보아 기억력 감퇴 모델이 제작되었음을 확인하였다. 베타 아밀로이드 단백질에 대한 용량의존성 실험에서 베타 아밀로이드 단백질만 투여한 군(대조군 2)의 머무름 시간이 92.10 ± 18.22초인데 반해 산조인과 양유근 5:1 중량비 복합추출물의 100, 200 및 400 mg/kg 투여군에서 각각 110.8 ± 16.83 (p < 0.05), 152.0 ± 54.81 (p < 0.05), 157.9 ± 79.54 (p < 0.05)초로 유의성 있는 증가를 보였다. 특히 산조인과 양유근 5:1 중량비 복합추출물 400 mg/kg의 용량에서 대조군의 58.5% 수준으로 도네페질 투여군과 비슷한 정도로 회복하는 것을 확인하였다.As a result, as can be seen in Table 8 and Figure 7, compared to the control group 3, the retention time of the beta-amyloid-only group (control group 2) was significantly reduced, confirming that the memory loss model was produced. In the dose-dependent experiment with beta amyloid protein, the retention time of the beta amyloid protein-only group (control 2) was 92.10 ± 18.22 sec, whereas the 100, 200 and 400 mg / kg group of the acid-join and yogurt 5: 1 weight ratio complex extracts. Significant increases were observed in 110.8 ± 16.83 ( p <0.05), 152.0 ± 54.81 ( p <0.05), and 157.9 ± 79.54 ( p <0.05) seconds, respectively. In particular, Sanjoin and Yang Yu-geun 5: 1 weight ratio of the composite extract 400 mg / kg dose of 58.5% of the control group was confirmed to recover to a similar degree as the donepezil administration.
Figure PCTKR2016010336-appb-T000008
Figure PCTKR2016010336-appb-T000008
실험예Experimental Example 5. 베타 아밀로이드 단백질에 의해 유도된 치매 모델을 이용한  5. Using a dementia model induced by beta amyloid protein 산조인과Sanjoin Family 양유근Yoo Keun Yang 5:1 중량비 복합추출물의 Y-미로 시험 Y-maze test of 5: 1 weight ratio composite extract
(1) 베타 아밀로이드 단백질 유도 치매 마우스의 제작(1) Fabrication of Beta Amyloid Protein-induced Dementia Mice
베타 아밀로이드 단백질 1-42 fragment (American peptide, USA)를 구입하여 0.9% 생리식염수에 1 mg/ml의 농도로 용해하였다. 그 후 37 ℃에서 24시간 동안 베타 아밀로이드 단백질을 응집시킨 후 사용하였다. 참고예 2의 마우스를 2% 아이소플루레인(isofluorane)으로 흡입마취를 유도한 후, 우측 뇌실에 3 μ를 해밀턴 실린지를 이용하여 투여하였다. 음성 대조군에는 0.9% 생리식염수를 투여하였다. 베타 아밀로이드 투여 직후 약물을 경구투여하였으며, 약물을 동량으로 1일 1회 총 7일간 투여하였다.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 ℃ for 24 hours. After inducing anesthesia with 2% isofluorane in mice of Reference Example 2, 3 μ 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.
(2) 실험 방법(2) Experiment method
실험예 5-(1)에 따른 마우스에 실시예에 따른 산조인과 양유근 5:1 중량비 복합추출물을 0.5% CMC에 녹인 후 여러 가지 용량(50, 100, 200 및 400 mg/kg)으로 7일간 경구 투여하였다. 양성 대조군(대조군 1)은 도네페질(donepezil) 5 mg/kg을 7일간 경구투여하고, 음성 대조군(대조군 3)에는 0.5% CMC를 7일간 경구투여하였다. 단회투여에 의한 효과를 피하기 위해 마지막 약물 투여 24시간 후에 Y-미로 시험을 실시하였으며, 방법은 상기 실험예 2와 동일하였다.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. To avoid the effect of single dose, Y-maze test was performed 24 hours after the last drug administration, and the method was the same as in Experimental Example 2.
(3) 실험 결과(3) experimental results
그 결과, 표 9 및 도 8에 나타나듯이 베타 아밀로이드 단백질만 투여한 군(대조군 2)의 변경 행동력(spontaneous alternation)이 51.61 ± 11.44%인데 반해 산조인과 양유근의 5:1 중량비 복합추출물 200 및 400 mg/kg 투여군에서 각각 63.04 ± 12.37 (p < 0.05), 64.71 ± 9.397 (p < 0.05)%로 유의성 있는 증가를 보였다. 또한, 각 구역으로 들어가는 총 횟수를 나타내는 총 출입수(total entry)에는 변화가 없는 것으로 나타나 변경 행동력(spontaneous alternation)이 마우스의 활동성 변화에 의해 나타난 것이 아님을 알 수 있었다.As a result, as shown in Table 9 and FIG. 8, the spontaneous alternation of the beta-amyloid-only group (control 2) was 51.61 ± 11.44%, whereas 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. In addition, 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.
Figure PCTKR2016010336-appb-T000009
Figure PCTKR2016010336-appb-T000009
제제예Formulation example 1.  One. 산제의Powder 제조 Produce
산조인과 양유근의 복합추출물 20 mg20 mg of extract of Sanjoin and Yang Yu-geun
유당 100 mg Lactose 100 mg
탈크 10 mg Talc 10 mg
상기의 성분들을 혼합하고 기밀포에 충진 하여 산제를 제조한다.The above ingredients are mixed and filled in an airtight cloth to prepare a powder.
제제예Formulation example 2. 정제의 제조 2. Preparation of Tablets
산조인과 양유근의 복합추출물 20 mg20 mg of extract of Sanjoin and Yang Yu-geun
옥수수전분 100 mg Corn starch 100 mg
유당 100 mg Lactose 100 mg
스테아린산 마그네슘 2 mg2 mg magnesium stearate
상기의 성분들을 혼합한 후 통상의 정제의 제조방법에 따라서 타정하여 정제를 제조한다.After mixing the above components, tablets are prepared by tableting according to a conventional method for preparing tablets.
제제예 3. 캅셀제의 제조 Formulation Example 3 Preparation of Capsule
산조인과 양유근의 복합추출물 20 mg20 mg of extract of Sanjoin and Yang Yu-geun
결정성 셀룰로오스 3 mg3 mg of crystalline cellulose
락토오스 14.8 mgLactose 14.8 mg
마그네슘 스테아레이트 0.2 mgMagnesium Stearate 0.2 mg
통상의 캡슐제 제조방법에 따라 상기의 성분을 혼합하고 젤라틴 캡슐에 충전하여 캡슐제를 제조한다.According to a conventional capsule preparation method, the above ingredients are mixed and filled into gelatin capsules to prepare capsules.
제제예Formulation example 4. 주사제의 제조 4. Preparation of Injectables
산조인과 양유근의 복합추출물 20 mg20 mg of extract of Sanjoin and Yang Yu-geun
만니톨 180 mgMannitol 180 mg
주사용 멸균 증류수 2974 mgSterile distilled water for injection 2974 mg
Na2HPO4,12H2O 26 mgNa 2 HPO 4 , 12H 2 O 26 mg
통상의 주사제의 제조방법에 따라 1 앰플당(2㎖) 상기의 성분 함량으로 제조한다.According to the conventional method for preparing an injection, the amount of the above ingredient is prepared per ampoule (2 ml).
제제예 5. 액제의 제조Formulation Example 5 Preparation of Liquid
산조인과 양유근의 복합추출물 20 mg20 mg of extract of Sanjoin and Yang Yu-geun
이성화당 10 g10 g of isomerized sugar
만니톨 5 g5 g of mannitol
정제수 적량Purified water
통상의 액제의 제조방법에 따라 정제수에 각각의 성분을 가하여 용해시키고 레몬 향을 적량 가한 다음 상기의 성분을 혼합한 다음 정제수를 가하여 전체를 정제수를 가하여 전체 100㎖로 조절한 후 갈색병에 충진 하여 멸균시켜 액제를 제조한다.According to the conventional method of preparing a liquid solution, 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.
제제예 6. 건강 식품의 제조Formulation Example 6 Preparation of Healthy Food
산조인과 양유근의 복합추출물 1000 mg1000 mg of Sanjoin and Yang Yu-geun extract
비타민 혼합물 적량Vitamin mixture proper amount
비타민 A 아세테이트 70 ㎍70 μg of Vitamin A Acetate
비타민 E 1.0 ㎎Vitamin E 1.0 mg
비타민 B1 0.13 ㎎Vitamin B1 0.13 mg
비타민 B2 0.15 ㎎Vitamin B2 0.15 mg
비타민 B6 0.5 ㎎Vitamin B6 0.5 mg
비타민 B12 0.2 ㎍0.2 μg of vitamin B12
비타민 C 10 ㎎ Vitamin C 10 mg
비오틴 10 ㎍10 μg biotin
니코틴산아미드 1.7 ㎎Nicotinic Acid 1.7 mg
엽산 50 ㎍Folate 50 ㎍
판토텐산 칼슘 0.5 ㎎Calcium Pantothenate 0.5mg
무기질 혼합물 적량Mineral mixture
황산제1철 1.75 ㎎Ferrous Sulfate 1.75 mg
산화아연 0.82 ㎎Zinc Oxide 0.82 mg
탄산마그네슘 25.3 ㎎Magnesium carbonate 25.3 mg
제1인산칼륨 15 ㎎Potassium monophosphate 15 mg
제2인산칼슘 55 ㎎Dibasic calcium phosphate 55 mg
구연산칼륨 90 ㎎Potassium Citrate 90 mg
탄산칼슘 100 ㎎ Calcium Carbonate 100 mg
염화마그네슘 24.8 ㎎Magnesium chloride 24.8 mg
상기의 비타민 및 미네랄 혼합물의 조성비는 비교적 건강식품에 적합한 성분을 바람직한 실시예로 혼합 조성하였지만, 그 배합비를 임의로 변형 실시하여도 무방하며, 통상의 건강식품 제조방법에 따라 상기의 성분을 혼합한 다음, 과립을 제조하고, 통상의 방법에 따라 건강식품 조성물 제조에 사용할 수 있다.Although the 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.
제제예 7. 건강 음료의 제조 Formulation Example 7 Preparation of Healthy Drink
산조인과 양유근의 복합추출물 1000 ㎎Sanjoin and Yang-Geun Complex Extract 1000 mg
구연산 1000 ㎎Citric acid 1000 mg
올리고당 100 g100 g oligosaccharides
매실농축액 2 gPlum concentrate 2 g
타우린 1g1 g of taurine
정제수를 가하여 전체 900 ㎖Add 900 ml of purified water
통상의 건강음료 제조방법에 따라 상기의 성분을 혼합한 다음, 약 1시간동안 85℃에서 교반 가열한 후, 만들어진 용액을 여과하여 멸균된 2ℓ 용기에 취득하여 밀봉 멸균한 뒤 냉장 보관한 다음 본 발명의 건강음료 조성물 제조에 사용한다. After mixing the above components in accordance with a conventional healthy beverage production method, and stirred and heated at 85 ℃ for about 1 hour, the resulting solution is filtered and obtained in a sterilized 2 L container, sealed sterilization and then refrigerated and stored in the present invention For the preparation of healthy beverage compositions.
상기 조성비는 비교적 기호음료에 적합한 성분을 바람직한 실시예로 혼합 조성하였지만, 수요계층, 요국가, 사용용도 등 지역적, 민족적 기호도에 따라서 그 배합비를 임의로 변형 실시하여도 무방하다.Although the composition ratio is mixed with a relatively suitable component for a preferred beverage in a preferred embodiment, the compounding ratio may be arbitrarily modified according to regional and ethnic preferences such as demand hierarchy, main country, and usage.
본 발명의 산조인 추출물 및 양유근 추출물을 포함하는 조성물은 인지기능장애 또는 퇴행성 뇌질환의 예방, 개선 또는 치료에 유용하게 사용될 수 있다.The 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.

Claims (17)

  1. 산조인 추출물 및 양유근 추출물을 포함하는 인지기능장애 또는 퇴행성 뇌질환의 예방 또는 치료용 약학적 조성물.Pharmaceutical composition for the prevention or treatment of cognitive dysfunction or degenerative brain disease, including Sanjoin extract and Yang yugeun extract.
  2. 제1항에 있어서, 산조인 추출물은 Zizypus jujuba var. spinosa의 에탄올 또는 수 추출물인 약학적 조성물.According to claim 1, Sanjoin extract is Zizypus jujuba var. Pharmaceutical composition which is an ethanol or water extract of spinosa .
  3. 제1항에 있어서, 양유근 추출물은 Codonopsis lanceloata의 에탄올 또는 수 추출물인 약학적 조성물.The method of claim 1, wherein the Yang Yugeun extract is Codonopsis Pharmaceutical composition which is an ethanol or water extract of lanceloata .
  4. 제1항에 있어서, 산조인 추출물 및 양유근 추출물은 전체 조성물 중에 1:1 내지 10:1의 중량비로 포함되는 약학적 조성물.The pharmaceutical composition of claim 1, wherein the Sanjoin extract and the Yangteun root extract are included in a weight ratio of 1: 1 to 10: 1 in the total composition.
  5. 제1항에 있어서, 산조인 추출물 및 양유근 추출물은 전체 조성물 중에 1:1 내지 6:1의 중량비로 포함되는 약학적 조성물.The pharmaceutical composition of claim 1, wherein the sanjoin extract and the yang-geun extract are included in a weight ratio of 1: 1 to 6: 1 in the total composition.
  6. 제1항에 있어서, 산조인 추출물 및 양유근 추출물은 전체 조성물 중에 5:1의 중량비로 포함되는 약학적 조성물.The pharmaceutical composition of claim 1, wherein the Sanjoin extract and the Yangteun root extract are included in a weight ratio of 5: 1 in the total composition.
  7. 제1항에 있어서, 퇴행성 뇌질환은 뇌졸중, 중풍, 건망증, 치매, 알츠하이머 질환, 파킨슨 질환 또는 헌팅턴 질환인 약학적 조성물.The pharmaceutical composition of claim 1, wherein the degenerative brain disease is stroke, stroke, forgetfulness, dementia, Alzheimer's disease, Parkinson's disease or Huntington's disease.
  8. 산조인 추출물 및 양유근 추출물을 포함하는 인지기능장애 또는 퇴행성 뇌질환의 예방 또는 개선용 건강기능식품 조성물.Health functional food composition for the prevention or improvement of cognitive dysfunction or degenerative brain disease, including Sanjoin extract and Yang Yu-geun extract.
  9. 제8항에 있어서, 산조인 추출물은 Zizypus jujuba var. spinosa의 에탄올 또는 수 추출물인 건강기능식품 조성물. The extract of claim 8, wherein the extract is Zizypus jujuba var. Functional food composition which is ethanol or water extract of spinosa .
  10. 제8항에 있어서, 양유근 추출물은 Codonopsis lanceloata의 에탄올 또는 수 추출물인 건강기능식품 조성물. 9. The extract of claim 8, wherein the galactic root extract is Codonopsis. Health functional food composition which is ethanol or water extract of lanceloata .
  11. 제8항에 있어서, 산조인 추출물 및 양유근 추출물은 전체 조성물 중에 1:1 내지 10:1의 중량비로 포함되는 건강기능식품 조성물. The dietary supplement composition according to claim 8, wherein the sanjoin extract and the yang-geun extract are included in a weight ratio of 1: 1 to 10: 1 in the total composition.
  12. 제8항에 있어서, 산조인 추출물 및 양유근 추출물은 전체 조성물 중에 1:1 내지 6:1의 중량비로 포함되는 건강기능식품 조성물.The dietary supplement composition according to claim 8, wherein the Sanjoin extract and the Yangteun root extract are included in a weight ratio of 1: 1 to 6: 1 in the total composition.
  13. 제8항에 있어서, 산조인 추출물 및 양유근 추출물은 전체 조성물 중에 5:1의 중량비로 포함되는 건강기능식품 조성물.The dietary supplement composition according to claim 8, wherein the sanjoin extract and the yang-geun extract are included in a weight ratio of 5: 1 in the total composition.
  14. 제8항에 있어서, 퇴행성 뇌질환은 뇌졸중, 중풍, 건망증, 치매, 알츠하이머 질환, 파킨슨 질환 또는 헌팅턴 질환인 건강기능식품 조성물.The dietary supplement composition of claim 8, wherein the degenerative brain disease is stroke, stroke, forgetfulness, dementia, Alzheimer's disease, Parkinson's disease or Huntington's disease.
  15. 산조인 추출물 및 양유근 추출물을 포함하는 인지기능장애 또는 퇴행성 뇌질환의 예방 또는 개선용 식품 조성물.Food composition for the prevention or improvement of cognitive dysfunction or degenerative brain disease, including Sanjoin extract and Yang yugeun extract.
  16. 제1항 내지 제15항 중 어느 한 항에 따른 조성물을 이를 필요로 하는 대상체에 투여함으로써, 인지기능장애 또는 퇴행성 뇌질환을 예방, 개선 또는 치료하는 방법.A method for preventing, ameliorating or treating cognitive dysfunction or degenerative brain disease by administering to a subject in need thereof a composition according to any one of claims 1 to 15.
  17. 인지기능장애 또는 퇴행성 뇌질환의 예방, 개선 또는 치료를 위한 약제 또는 식품의 제조를 위한 제1항 내지 제15항 중 어느 한 항에 따른 조성물의 용도.Use of a composition according to any one of claims 1 to 15 for the manufacture of a medicament or food for the prevention, amelioration or treatment of cognitive dysfunction or degenerative brain disease.
PCT/KR2016/010336 2015-09-18 2016-09-13 Pharmaceutical composition for preventing or treating cognitive function disorder or degenerative brain disease WO2017048051A1 (en)

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KR20050047779A (en) * 2003-11-18 2005-05-23 주식회사 에스티씨나라 Composition for preventing or treating dementia and improving cognitive function comprising oriental medicine extracts as active ingredient
KR20050092292A (en) * 2004-03-15 2005-09-21 주식회사 크라우젠 Herbal composition effective in improving memory
KR20120053604A (en) * 2010-11-18 2012-05-29 강원대학교산학협력단 Composition for preventing or treating the brain ischemia disease containing extract of codonopsis lanceolata
KR20130001764A (en) * 2011-06-28 2013-01-07 삼성중공업 주식회사 Pipe clamp for ship
KR20140077382A (en) * 2012-12-14 2014-06-24 경희대학교 산학협력단 Pharmaceutical Composition comprising lancemaside A or metabolite thereof for prevention and treatment of cognitive disorder

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KR20050092292A (en) * 2004-03-15 2005-09-21 주식회사 크라우젠 Herbal composition effective in improving memory
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