WO2012033329A2 - Composition containing oenanthe javanica extract as an active ingredient for preventing or treating learning disabilities or memory disorders, and method for preparing same - Google Patents

Composition containing oenanthe javanica extract as an active ingredient for preventing or treating learning disabilities or memory disorders, and method for preparing same Download PDF

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WO2012033329A2
WO2012033329A2 PCT/KR2011/006591 KR2011006591W WO2012033329A2 WO 2012033329 A2 WO2012033329 A2 WO 2012033329A2 KR 2011006591 W KR2011006591 W KR 2011006591W WO 2012033329 A2 WO2012033329 A2 WO 2012033329A2
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extract
memory
disorders
preventing
buttercup
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PCT/KR2011/006591
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French (fr)
Korean (ko)
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WO2012033329A3 (en
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서유헌
신기영
원범영
이혜진
이형근
정경희
김기명
위지향
정경옥
성혜미
신현경
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주식회사 브레인트로피아
재단법인 전라남도생물산업진흥재단
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Priority to CN201180043211.8A priority Critical patent/CN103153322B/en
Publication of WO2012033329A2 publication Critical patent/WO2012033329A2/en
Publication of WO2012033329A3 publication Critical patent/WO2012033329A3/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/23—Apiaceae or Umbelliferae (Carrot family), e.g. dill, chervil, coriander or cumin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia

Definitions

  • the present invention relates to a composition for preventing or treating learning ability or memory impairment containing buttercup extract as an active ingredient, and a method of manufacturing the same. More specifically, acetylcholine in a buttercup, in particular field parsley, is used for food. Esterase (AChE) to inhibit the activity, or to extract the active ingredient that can prevent or treat learning or memory impairment is to use as a pharmaceutical composition or health functional food.
  • AChE Esterase
  • Buttercup is called root root, root root, and swimming, and it grows throughout Korea, and it is a savory vegetable that is widely distributed from the temperate zone to the tropics such as Sakhalin Island, yearly China, Japan, Southeast Asia, Oceania, etc. .
  • Buttercups are divided into paddy buttercups and field buttercups according to the cultivation method.
  • Paddy parsley is a hollow parsley that is cultivated by trapping water in paddy fields from the beginning to harvest. Buttercup is initially grown hydroponicly like paddy field but is cultivated after draining water. It is called field buttercup because it is cultivated in the state of the field, and the inside of the stem is not empty and the contents are full.
  • buttercup parsley parsley is effective for jaundice, gynecology, headache or vomiting after drinking.
  • the buttercup contains flavonoids and cholin essential oils.
  • Quinoline-based alkaloids include rutamin, r-pagarin, and coumarin, and these ingredients help to protect against liver, antimutation and antioxidant activity.
  • it is known to have an excellent effect on the treatment of high blood pressure as well as the removal of hangover after drinking.
  • dementia is a degenerative disorder characterized by brain disorders such as cell death and memory loss, which is estimated to occur in about 10% of people over 65 years old and about 50% of elderly people over 80 years old. do. As the aging population has recently increased, the incidence rate is expected to increase more rapidly. Therefore, dementia has become a serious social and economic problem in modern society.
  • Alzheimer's dementia There are various causes of dementia, which can be divided into Alzheimer's disease, vascular dementia, other alcoholism, trauma, and dementia resulting from Parkinson's disease. Since Alzheimer's dementia is present in more than half of patients with dementia, research on dementia has been focused on Alzheimer's dementia.
  • Alzheimer's dementia The pathogenesis of Alzheimer's dementia is unclear, but to date, decreased acetylcholine function in the central nervous system, deposition in brain cells of senile plaques based on amyloid beta (A ⁇ ) protein, or cells It is known to be closely related to the appearance of a neurofibrillary tangle mainly composed of external superphosphorylated tau protein.
  • a ⁇ amyloid beta
  • the existing treatment for dementia is an acetylcholinease inhibitor that can inhibit the activity of acetylcholine esterase (AchE), an enzyme of acetylcholine, or acetylcholine synthesis that can maintain acetylcholine at a constant level.
  • AchE acetylcholine esterase
  • Substances such as precursors and acetylcholine receptor activators (Receptor agonist) are the majority.
  • tacrine, aricept and galantamine, acetylcholine synthetic precursors are lecitin and acetylcholine.
  • Receptor activators include RS-86, nicotine, and the like.
  • the present invention aims to provide a pharmaceutical composition which is obtained from natural products, has little toxicity and side effects, has a strong anticholinesterase effect, and prevents or treats learning or memory impairment.
  • the present invention is to provide a health functional food that is obtained from natural products, has little toxicity and side effects, has a strong anticholinesterase effect and improves learning ability or memory.
  • the present invention is characterized by a pharmaceutical composition for the prevention or treatment of learning disorders or memory disorders using the buttercup extract as an active ingredient.
  • the buttercup is characterized in that it is a field buttercup.
  • the pharmaceutical composition for preventing or treating learning disorders or memory disorders of the present invention is characterized by being for oral administration.
  • the extract is characterized in that the extract is available in a solvent selected from a lower alcohol having 1 to 4 carbon atoms, or an aqueous solution of the lower alcohol.
  • the aqueous alcohol solution is characterized by being an aqueous alcohol solution having a mixing ratio of lower alcohol of 10 to 95 (v / v)%.
  • the method of preparing a buttercup extract for preventing or treating learning disorders or memory disorders according to the present invention is mixed with a lower alcohol aqueous solution having 1 to 4 carbon atoms of 20 to 200 times the dry buttercup weight, and extracted for 4 to 20 hours at 50 to 90 ° C. Characterized in that.
  • the lower alcohol aqueous solution is 50 to 80 (v / v)% ethanol aqueous solution, and extracted with the ethanol aqueous solution, the extract is ethyl acetate Or it is characterized in that the extraction with butanol.
  • the present invention provides a health functional food for improving learning ability or memory with the buttercup extract as an active ingredient.
  • the buttercup is characterized in that the field buttercup.
  • the health functional food is characterized in that the powder, granules, tablets, capsules or beverage form.
  • Buttercup extract according to the present invention is a natural-derived extract with little side effects or toxicity significantly inhibits the activity of acetylcholinesterase (AChE), and prevents memory impairment by administration of scopolamine, a drug that induces dementia or memory loss. It has the effect of preventing and shows the effect of treating memory disorders caused by alcohol or stress.
  • AChE acetylcholinesterase
  • AChE acetylcholinesterase
  • Figure 2 is a graph comparing the inhibition rate of acetylcholinesterase activity of the re-extracted extract extracted from the alcohol extract of buttercup with various solvents.
  • Figure 3 is a graph comparing the inhibition rate of acetylcholinesterase activity of paddy field extract and field buttercup extract.
  • the present invention provides a composition that is effective in inhibiting the activity of acetylcholinesterase (AChE) and improving learning ability or memory in buttercups, a pharmaceutical composition for preventing or treating learning disorders or memory disorders, or health functional foods for improving learning ability or memory. Is to use.
  • AChE acetylcholinesterase
  • Buttercup in the present invention belongs to the asteraceae scientific name Umbelliferaceae ( Ostericum coreanum ), Oenanthe stonilifera ( Oenanthe stonilifera ), Oenanthe javanica ( Oenanthe javanica ), etc., preferably Crab is Korean parsley.
  • Buttercup can be used both as water parsley, which is usually hydroponicly grown in paddy fields, and field parsley, called fire parsley, which is grown in the field.However, the field buttercup has the inhibitory activity of acetylcholinesterase (AChE) compared to the paddy field. It is more preferable at the point that it is excellent and the effect of preventing memory damage by a drug is excellent.
  • AChE acetylcholinesterase
  • a lower alcohol having 1 to 4 carbon atoms, or an aqueous solution of the lower alcohol may be used.
  • the lower alcohol having 1 to 4 carbon atoms for example, methanol, ethanol, butanol, propanol, isopropanol and the like can be used, and preferably ethanol is used.
  • An aqueous aqueous solution of)%, more preferably an aqueous alcohol solution having 50 to 80 (v / v)% is used.
  • the extract is extracted with an aqueous ethanol solution having 50 to 80 (v / v)%, and the extract is extracted with ethyl acetate or butanol as an extract, which is excellent in inhibiting activity of acetylcholinesterase (AChE). It is advantageous in that.
  • Buttercup extract of the present invention may be prepared by an extraction method such as stirring extraction, reflux cooling extraction, cold needle extraction, ultrasonic extraction or supercritical extraction using the solvent,
  • composition comprising the buttercup extract of the present invention as an active ingredient can be used for the prevention and treatment of Alzheimer's dementia, vascular dementia, other alcoholism, trauma, Parkinson's disease, dementia or cognitive dysfunction, especially Alzheimer's disease. Suitable for the treatment of dementia.
  • composition of the present invention includes the buttercup extract in an amount of 0.1 to 50% by weight based on the total weight of the composition.
  • composition as described above is not necessarily limited thereto, and may vary according to the condition of the patient and the type and extent of the disease.
  • composition comprising the buttercup extract of the present invention as an active ingredient may further comprise suitable carriers, excipients and diluents commonly used in the manufacture of pharmaceutical compositions.
  • compositions comprising the buttercup extract according to the present invention as an active ingredient, oral formulations, such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, external preparations, suppositories, and sterile injectable solutions, respectively, according to conventional methods
  • Carriers, excipients and diluents which may be used in the form of a formulation, which may be included in the composition containing the extract as an active ingredient, 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 Can be mentioned.
  • 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.
  • 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.
  • base of the suppository witepsol, macrogol, tween 61, cacao butter, laurin butter, glycerogelatin and the like can be used.
  • compositions of the present invention vary depending on the condition and weight of the patient, the extent of the disease, the form of the drug, the route of administration and the duration, and may be appropriately selected by those skilled in the art.
  • the composition of the present invention is preferably administered at 0.01 mg / kg to 10 g / kg, preferably 1 mg / kg to 1 g / kg based on the solid content of the buttercup extract. Administration may be administered once a day or may be divided several times. Therefore, the above dosage does not limit the scope of the present invention in any aspect.
  • 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. Especially preferably, the buttercup extract of the present invention is superior in preventing memory damage compared to intraperitoneal administration.
  • the present invention provides a dietary supplement comprising a buttercup extract and a food supplement acceptable food supplement additive exhibiting a learning or memory enhancing effect.
  • composition comprising the buttercup extract of the present invention as an active ingredient includes, for example, various foods, beverages, gums, teas, vitamin complexes, health supplements, and the like, and are powders, granules, tablets, capsules, or beverages. Available in form.
  • Buttercup extract itself of the present invention is a drug that can be used with confidence even when taken for a long time for the purpose of prevention because there is little toxicity and side effects.
  • the amount of the extract is generally based on solids, health functional food in the form of powder, granules, tablets, capsules, etc. of the present invention.
  • the amount of the extract in the case of can be added in an amount of 0.01 to 15% by weight of the total food weight
  • a health functional food in the form of a beverage can be added in a ratio of 0.02 to 10 g, preferably 0.3 to 1 g based on 100 ml of the beverage.
  • the health functional food of the beverage form of the present invention contains the extract as an essential ingredient in the ratio indicated, and there are no special limitations in the liquid component, and it may contain various flavors or natural carbohydrates as additional ingredients, such as ordinary drinks. Can be.
  • natural carbohydrates are conventional monosaccharides such as disaccharides such as glucose and fructose, such as maltose, sucrose and the like, and polysaccharides such as dextrin, cyclodextrin and the like.
  • Sugars and sugar alcohols such as xylitol, sorbitol, and erythritol.
  • natural flavoring agents such as, tauumatin, stevia extract (for example, rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.) can be advantageously used.
  • the proportion of natural carbohydrates is generally about 1-20 g, preferably about 5-12 g per 100 ml of the composition of the present invention.
  • the composition of the present invention includes various nutrients, vitamins, minerals (electrolytes), flavors such as synthetic flavors and natural flavors, coloring and neutralizing agents (such as cheese and chocolate), pectic acid and salts thereof, alginic acid and its Salts, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohols, carbonation agents used in carbonated beverages, and the like.
  • the compositions of the present invention may also contain pulp for the production of natural fruit juices and fruit juice beverages and vegetable beverages. These components can be used independently or in combination. The proportion of such additives is not so critical but is generally selected from the range of 0 to about 20 parts by weight per 100 parts by weight of the composition of the present invention.
  • Extracts of ethanol aqueous solution of baeknyeon fruit, pomegranate, citron, fig, fresh vinegar, jujube and paddy parsley 70 (v / v)% were prepared to compare the inhibitory activity of acetylcholinesterase.
  • Each ethanol aqueous solution extract was extracted with 10 ml of dry sample 600 ml of ethanol (ethanol content 70 (v / v)%) without reflux at 60 °C for 8 hours, filtered to remove the residue 50 to 60 mmHg and 30 The resultant was evaporated to concentration under the condition of 40 to 40 ° C., and the resultant concentrate was hot-air dried to obtain an ethanol extract powder.
  • DMSO dimethyl sulfoxide
  • buffer I 100 mM phosphate
  • Blank was added with saline instead of enzyme.
  • acetylthiocholine iodine solution it was also confirmed that a slight non-specific reaction does not appear when measuring the ethanol extract powder and enzyme activity.
  • baeknyeoncho fruit, pomegranate and citron extract showed 8 to 11% inhibition of acetylcholinesterase activity, but the non-parsley extract exhibited an activity inhibition rate of 23.5%, more than 2 times, fig, fresh vinegar and jujube Inhibition rate of the enzyme activity of the extract was less than 5%.
  • the inhibition rate of acetylcholinesterase activity of the non-parsley hot water extract powder and the alcohol extract powder was measured by the method of Experimental Example 1, and compared with DHED added to 37.8 ⁇ M as a positive control group, the results are shown in Table 1. .
  • the AChE activity experiment was repeated five times to test the significance of the results by a one-way ANOVA test.
  • the inhibition rate of acetylcholinesterase activity of each fraction extract was measured by the method of Experimental Example 1 and is shown in FIG. 2.
  • ethyl acetate and butanol extract showed the greatest inhibition rate of enzyme activity, and the active ingredient which inhibits acetylcholinesterase activity of the buttercup extract by E-alcohol extraction was considered to be in ethyl acetate layer or butanol layer. It became.
  • Non- buttercup extract powder and field buttercup extract powder were added at a concentration of 500 ⁇ g / ml, DHED was added at a concentration of 100 ⁇ M as a positive control group, and the inhibition rate of acetylcholinesterase activity was measured by the method of Experimental Example 1 and is shown in FIG. 3.
  • the field buttercup extract was prepared by the same extraction method, and even though the same concentration was used, it was confirmed that it was more than two times higher than the inhibition rate of the enzyme activity of the non buttercup extract, and showed the same level of inhibition of enzyme activity as the DHED of 50 ⁇ M.
  • the experimental instrument is a shuttle box (50 ⁇ 15 ⁇ 40 cm) with an electric grid floor.
  • the box is divided into partition doors and forms a room of 25 ⁇ 15 cm.
  • noise and noise 60 dB or less, and whether the learning and memory impairment impaired by scopolamine in rats can be treated through the administration of Paddy Buttercup and Field Buttercup extract of Experiment 4 I looked at it.
  • the memory loss of the scopolamine-administered group was obvious.
  • the memory reduced by scopolamine was restored by tacrine, an anticholinesterase that was previously used as a dementia drug.
  • the recovery of memory lowered by scopolamine was more effective in the field buttercups than in the field buttercups, and the memory recovery effect of the field buttercups was better than that of tacrine.
  • the therapeutic effect of memory-lowering memory was carried out for 4 weeks.
  • Alcohol was intraperitoneally administered at a 2.5 g / kg dose daily.
  • Doses of field buttercup extract were orally administered at 10 mg / kg and the positive control linoleic acid at 10 mg / kg for 4 weeks.
  • the Y-maze test was performed after 4 weeks of administration.
  • the Y-maze test is a test method for verifying spatial perception, consisting of three arms of the same size and a black plastic maze. Each arm consists of 80 ⁇ 35 ⁇ 15 cm and each arm maintains the same angle. The rat is placed at the end of the arm and allowed to move freely for 10 minutes. Record the order in which the rat enters each arm. Scores are given when three different arms are selected in succession. These scores (% of alternation) are shown in Table 4 by comparing the groups.
  • 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 and dissolved in purified water, lemon flavor is added to the mixture, and then the above ingredients are mixed, purified water is added to adjust the total amount to 100 ml, and then filled in a brown bottle.
  • the solution is prepared by sterilization.
  • Vitamin B6 0.5 mg
  • composition ratio of the vitamin and mineral mixture is a composition suitable for a relatively healthy 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 a composition that is relatively suitable for the preferred beverage in a preferred embodiment
  • the composition ratio may be arbitrarily modified according to regional and ethnic preferences such as demand hierarchy, demand country, and usage.

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Abstract

The present invention relates to a composition containing Oenanthe javanica extract as an active ingredient for preventing or treating learning disabilities or memory disorders, and to a method for preparing same. More particularly, the present invention relates to a composition which can be used as a pharmaceutical composition or functional health food and which is prepared by extracting an active ingredient from Oenanthe javanica, which is an edible herb, wherein the active ingredient provides the function of preventing acetylcholinesterase (AChE) from being activated, or the function of preventing or treating learning disability or memory disorder.

Description

미나리 추출물을 유효성분으로 함유하는 학습능력 또는 기억력 장애 예방 또는 치료용 조성물 및 그 제조방법A composition for preventing or treating learning ability or memory disorders containing buttercup extract as an active ingredient, and a method of manufacturing the same
본 발명은 미나리 추출물을 유효성분으로 함유하는 학습능력 또는 기억력 장애 예방 또는 치료용 조성물 및 그 제조방법에 관한 것으로, 더욱 상세하게는 식용으로 사용되는 향신채소 중 하나인 미나리, 특히 밭미나리에서 아세틸콜린에스터라제(AChE)의 활성을 억제하거나, 학습능력 또는 기억력 장애를 예방 또는 치료할 수 있는 유효성분을 추출하여 약학 조성물 또는 건강기능식품으로 활용하는 것이다.The present invention relates to a composition for preventing or treating learning ability or memory impairment containing buttercup extract as an active ingredient, and a method of manufacturing the same. More specifically, acetylcholine in a buttercup, in particular field parsley, is used for food. Esterase (AChE) to inhibit the activity, or to extract the active ingredient that can prevent or treat learning or memory impairment is to use as a pharmaceutical composition or health functional food.
미나리는 근채(芹菜), 수근(水芹), 수영(水英)이라고 불리고, 우리나라 전역에 자생하고 있으며 사할린섬, 중국대륙, 일본, 동남아시아, 오세아니아 등 아한대, 온대로부터 열대까지 널리 분포하는 향신채소이다.Buttercup is called root root, root root, and swimming, and it grows throughout Korea, and it is a savory vegetable that is widely distributed from the temperate zone to the tropics such as Sakhalin Island, Mainland China, Japan, Southeast Asia, Oceania, etc. .
미나리는 재배방식에 따라 논 미나리와 밭 미나리로 구분하는데, 논 미나리는 처음부터 수확시까지 논에 물을 가두어 재배한 미나리로 줄기를 잘라보면 안이 비어 있는 것으로 조직이 유연하며 물 미나리라고도 하고, 밭 미나리는 처음에는 논 미나리와 유사하게 수경재배하다가 나중에 물을 빼고 재배하는 것으로, 밭 상태로 관리하여 재배한다고 하여 밭 미나리라고 부르며, 줄기 안쪽이 비어 있지 않고 내용물이 꽉 차있는 것이다. Buttercups are divided into paddy buttercups and field buttercups according to the cultivation method.Paddy parsley is a hollow parsley that is cultivated by trapping water in paddy fields from the beginning to harvest. Buttercup is initially grown hydroponicly like paddy field but is cultivated after draining water. It is called field buttercup because it is cultivated in the state of the field, and the inside of the stem is not empty and the contents are full.
보통 미나리라고 칭하는 것은 논 미나리로서, 미나리는 동의보감에 황달, 부인병, 음주 후의 두통이나 구토에 효과적인 것으로 나오며, 최근의 각종 연구에 따르면 미나리에 플라보노이드(flavonods), 콜린(cholin) 정유가 포함되어 있고, 퀴놀린(quinoline)계의 알칼로이드(alkaloid)로 루타민(rutamin)과 r-파가린(r-pagarin), 쿠마린(cumarin) 등도 함유하고 있고, 이러한 성분들로 인하여 간 보호작용, 항돌연변이 및 항산화작용, 고혈압 치료효과뿐만 아니라 음주 후 숙취제거에 탁월한 효과가 있는 것으로 알려져 있다. Commonly referred to as buttercup parsley, parsley is effective for jaundice, gynecology, headache or vomiting after drinking. According to recent studies, the buttercup contains flavonoids and cholin essential oils. Quinoline-based alkaloids include rutamin, r-pagarin, and coumarin, and these ingredients help to protect against liver, antimutation and antioxidant activity. In addition, it is known to have an excellent effect on the treatment of high blood pressure as well as the removal of hangover after drinking.
한편, 치매(dementia)란 뇌세포 사멸 및 기억력 감퇴 등 뇌기능의 전반적인 장애가 나타나는 것을 특징으로 하는 퇴행성 질환으로, 65세 이상인 사람들의 약 10%, 80세 이상의 노인들의 약 50% 이상에서 나타나는 것으로 추정된다. 최근 노령화 인구가 증가하게 되면서 그 발병속도는 더욱 급속하게 증가할 것으로 예상되므로, 치매는 현대사회의 심각한 사회적, 경제적 문제로 대두되고 있다.On the other hand, dementia is a degenerative disorder characterized by brain disorders such as cell death and memory loss, which is estimated to occur in about 10% of people over 65 years old and about 50% of elderly people over 80 years old. do. As the aging population has recently increased, the incidence rate is expected to increase more rapidly. Therefore, dementia has become a serious social and economic problem in modern society.
치매의 원인은 다양해서 알츠하이머성 치매(Alzheimer's disease), 혈관성 치매, 기타 알콜 중독, 외상, 파킨슨병의 후유증으로 오는 치매로 구분된다. 치매 환자의 절반 이상에서 알츠하이머성 치매가 나타나고 있기 때문에, 치매에 대한 연구는 알츠하이머성 치매를 중점으로 하여 진행되고 있다.There are various causes of dementia, which can be divided into Alzheimer's disease, vascular dementia, other alcoholism, trauma, and dementia resulting from Parkinson's disease. Since Alzheimer's dementia is present in more than half of patients with dementia, research on dementia has been focused on Alzheimer's dementia.
알츠하이머성 치매의 발병기전은 명확하게 밝혀져 있지 않으나, 현재까지는 중추신경계에서 아세틸콜린 기능의 감소, 아밀로이드 베타(amyloid beta, Aβ) 단백질을 주성분으로 하는 노인반(senile plaque)의 뇌세포 내 침착, 또는 세포 외부의 과인산화된 타우 단백질을 주성분으로 하는 신경섬유덩어리(Neurofibrillary tangle)의 출현 등과 밀접한 관련이 있는 것으로 알려져 있다.The pathogenesis of Alzheimer's dementia is unclear, but to date, decreased acetylcholine function in the central nervous system, deposition in brain cells of senile plaques based on amyloid beta (Aβ) protein, or cells It is known to be closely related to the appearance of a neurofibrillary tangle mainly composed of external superphosphorylated tau protein.
기존에는 상기 원인 중 콜린성 신경계의 기능 저하와 기억력 저하 사이의 상관관계를 밝혀주는 연구결과가 많이 보고되었으므로, 콜린 신경계를 보충하고 개선함으로써 치매를 치료하고자 하는 노력이 계속되어 왔다.In the past, many studies have revealed the correlation between the function of the cholinergic nervous system and memory loss, and thus, efforts to treat dementia by supplementing and improving the choline nervous system have been continued.
따라서 기존의 치매 치료제는 뇌에서 아세틸콜린의 분해효소인 아세틸콜린 에스터라제(AchE)의 활성을 억제할 수 있는 아세틸콜린분해 억제제, 또는 아세틸콜린의 농도를 일정수준으로 유지해 줄 수 있는 아세틸콜린 합성전구체 및 아세틸콜린 수용체 활성제(Receptor agonist) 등의 물질들이 대부분이다.Therefore, the existing treatment for dementia is an acetylcholinease inhibitor that can inhibit the activity of acetylcholine esterase (AchE), an enzyme of acetylcholine, or acetylcholine synthesis that can maintain acetylcholine at a constant level. Substances such as precursors and acetylcholine receptor activators (Receptor agonist) are the majority.
그 예로, 아세틸콜린분해 억제제로는 FDA의 승인을 받아 국내에서도 시판사용중인 타크린(tacrine), 아리셉트(aricept) 및 갈란타민(galantamine), 아세틸콜린 합성전구체로는 레시틴(lecitin), 그리고 아세틸콜린 수용체 활성제로는 RS-86, 니코틴(nicotine) 등이 있다.For example, tacrine, aricept and galantamine, acetylcholine synthetic precursors are lecitin and acetylcholine. Receptor activators include RS-86, nicotine, and the like.
그러나 치매가 진행되면서 아세틸콜린성 신경세포 뿐 아니라 신경세포의 대다수를 차지하는 글루탐산성 신경세포들도 퇴화하기 때문에, 아세틸콜린의 활성 증진에 중점을 둔 상기 방법은 일시적이고 미약한 치매 예방 및 치료효과만을 거둘 뿐이다. 또한 타크린을 비롯한 대부분의 약물들은 심각한 간독성, 구토, 오심 또는 설사 등의 부작용 때문에 아직까지 그 사용 여부에 대해 논란의 여지가 많은 상태이다.However, as dementia progresses, not only acetylcholine neurons but also glutamic acid neurons, which occupy the majority of neurons, deteriorate the temporary and weak dementia prevention and treatment. It is only. In addition, most drugs, including tacrine, remain controversial as to their use, due to side effects such as severe hepatotoxicity, vomiting, nausea or diarrhea.
또한 현대사회는 복잡하고 전문화되는 추세이며 그에 따라 많은 정보량과 학습량이 요구되므로 효과적인 두뇌활동이 필요하게 되고 있다. 그러나 많은 사람들이 노화, 질병, 약물이나 스트레스에 의한 기억력의 감퇴로 고통받고 있으며 이러한 인간의 수명이 연장되어 감에 따라 고도의 정신활동이 요구되고 있다. 이러한 상황을 적절히 대처하기 위하여 두뇌를 맑게 하고 기억력을 증진시켜 정신활동을 필요로 하는 등의 노력이 다양하게 시도되고 있고 이러한 기능을 효과적으로 증진시킬 수 있는 의약품, 기능성 식품등의 개발이 당업계에 요구되고 있다.In addition, the modern society is a complex and specialized trend, and accordingly, a large amount of information and learning is required, and thus effective brain activity is required. However, many people are suffering from memory loss due to aging, disease, drugs, or stress, and as these human lifespans are extended, high mental activity is required. In order to cope with this situation, various efforts have been made to clear the brain, improve memory, and require mental activities, and the development of medicines, functional foods, etc. that can effectively promote these functions is required in the art. It is becoming.
따라서 민간이나 한방에서 널리 이용되어 별도의 부작용이 적은 천연물을 대상으로 효과적으로 학습능력 및 기억력을 증진시킬 수 있고, 학습장애 또는 기억력 장애를 예방하거나 치료하며, 아세틸콜린에스터라제(AChE)의 활성을 억제하는 활성을 가진 천연물을 검색하던 중 미나리 추출물, 특히 밭 미나리 추출물이 경구 투여시 상기 활성을 매우 현저히 나타냄을 확인하게 되어 본 발명을 완성하게 되었다.Therefore, it is widely used in private or oriental medicine, and can effectively improve learning ability and memory for natural products with few side effects, prevent or treat learning disorders or memory disorders, and activate acetylcholinesterase (AChE) activity. While searching for natural products with inhibitory activity, it was confirmed that the buttercup extract, in particular, the field buttercup extract, exhibits the activity very significantly when orally administered, thereby completing the present invention.
본 발명은 천연물로부터 얻어지는 것으로 독성과 부작용이 거의 없고 강력한 항콜린에스터라제 효과를 가지며 학습능력이나 기억력 장애를 예방 또는 치료하는 약학 조성물을 제공하는 것을 목적으로 한다.The present invention aims to provide a pharmaceutical composition which is obtained from natural products, has little toxicity and side effects, has a strong anticholinesterase effect, and prevents or treats learning or memory impairment.
또한 본 발명은 미나리로부터 가장 높은 항콜리에스터라제 효과를 가지는 추출물의 제조방법을 제공하는데 그 목적이 있다.It is another object of the present invention to provide a method for preparing an extract having the highest anti-cholesterase effect from buttercup.
또한 본 발명은 천연물로부터 얻어지는 것으로 독성과 부작용이 거의 없고 강력한 항콜린에스터라제 효과를 가지며 학습능력이나 기억력을 증진시키는 건강기능식품을 제공하는 것을 목적으로 한다.In another aspect, the present invention is to provide a health functional food that is obtained from natural products, has little toxicity and side effects, has a strong anticholinesterase effect and improves learning ability or memory.
본 발명은 미나리 추출물을 유효성분으로 하는 학습장애 또는 기억력 장애 예방 또는 치료용 약학 조성물을 특징으로 한다.The present invention is characterized by a pharmaceutical composition for the prevention or treatment of learning disorders or memory disorders using the buttercup extract as an active ingredient.
본 발명의 학습장애 또는 기억력 장애 예방 또는 치료용 약학 조성물에서, 상기 미나리는 밭미나리인 것을 특징으로 한다.In the pharmaceutical composition for preventing or treating learning disorders or memory disorders of the present invention, the buttercup is characterized in that it is a field buttercup.
본 발명의 학습장애 또는 기억력 장애 예방 또는 치료용 약학 조성물은, 경구 투여용인 것을 특징으로 한다.The pharmaceutical composition for preventing or treating learning disorders or memory disorders of the present invention is characterized by being for oral administration.
본 발명의 학습장애 또는 기억력 장애 예방 또는 치료용 약학 조성물에서, 상기 추출물은 탄소수 1 내지 4의 저급 알코올, 또는 상기 저급 알코올의 수용액으로로부터 선택된 용매에 가용한 추출물인 것을 특징으로 한다.In the pharmaceutical composition for preventing or treating learning disorders or memory disorders of the present invention, the extract is characterized in that the extract is available in a solvent selected from a lower alcohol having 1 to 4 carbon atoms, or an aqueous solution of the lower alcohol.
본 발명의 학습장애 또는 기억력 장애 예방 또는 치료용 약학 조성물에서, 상기 알코올 수용액은 저급 알코올의 혼합비가 10 내지 95(v/v)%인 알코올 수용액임을 특징으로 한다.In the pharmaceutical composition for preventing or treating learning disorders or memory disorders of the present invention, the aqueous alcohol solution is characterized by being an aqueous alcohol solution having a mixing ratio of lower alcohol of 10 to 95 (v / v)%.
또한 본 발명의 학습장애 또는 기억력 장애 예방 또는 치료용 미나리 추출물의 제조방법은, 건조 미나리 중량의 20 내지 200배의 탄소수 1 내지 4의 저급 알코올 수용액을 혼합하여 50 내지 90 ℃에서 4 내지 20 시간 추출하는 것을 특징으로 한다.In addition, the method of preparing a buttercup extract for preventing or treating learning disorders or memory disorders according to the present invention is mixed with a lower alcohol aqueous solution having 1 to 4 carbon atoms of 20 to 200 times the dry buttercup weight, and extracted for 4 to 20 hours at 50 to 90 ° C. Characterized in that.
본 발명의 학습장애 또는 기억력 장애 예방 또는 치료용 미나리 추출물의 제조방법에서, 상기 저급 알코올 수용액은 50 내지 80(v/v)%의 에탄올 수용액이고, 상기 에탄올 수용액으로 추출한 후, 그 추출물을 에틸아세테이트 또는 부탄올로 추출하는 것을 특징으로 한다.In the method of producing a buttercup extract for preventing or treating learning disorders or memory disorders of the present invention, the lower alcohol aqueous solution is 50 to 80 (v / v)% ethanol aqueous solution, and extracted with the ethanol aqueous solution, the extract is ethyl acetate Or it is characterized in that the extraction with butanol.
또한 본 발명은 미나리 추출물을 유효성분으로 하는 학습능력 또는 기억력 증진용 건강기능식품을 제공한다.In another aspect, the present invention provides a health functional food for improving learning ability or memory with the buttercup extract as an active ingredient.
본 발명의 학습능력 또는 기억력 증진용 건강기능식품에서, 상기 미나리는 밭 미나리인 것을 특징으로 한다.In the health functional food for learning or memory enhancement of the present invention, the buttercup is characterized in that the field buttercup.
본 발명의 학습능력 또는 기억력 증진용 건강기능식품에서, 상기 건강기능식품의 형태는 분말, 과립, 정제, 캡슐 또는 음료 형태인 것을 특징으로 한다.In the health functional food for learning or memory enhancement of the present invention, the health functional food is characterized in that the powder, granules, tablets, capsules or beverage form.
본 발명에 따른 미나리 추출물은 부작용이나 독성이 거의 없는 천연물 유래 추출물로서 아세틸콜린에스터라제(AChE)의 활성을 현저히 억제하며, 치매 또는 기억력 감퇴를 유도하는 약물인 스코폴라민 투여에 의한 기억력 손상을 예방하는 효과를 가지며, 알코올 또는 스트레스에 의한 기억력 장애를 치료하는 효과를 나타낸다.Buttercup extract according to the present invention is a natural-derived extract with little side effects or toxicity significantly inhibits the activity of acetylcholinesterase (AChE), and prevents memory impairment by administration of scopolamine, a drug that induces dementia or memory loss. It has the effect of preventing and shows the effect of treating memory disorders caused by alcohol or stress.
도 1은 미나리를 비롯한 각종 천연물의 아세틸콜린에스터라제(AChE)의 활성 억제율을 비교한 그래프이다.1 is a graph comparing the activity inhibition rate of acetylcholinesterase (AChE) of various natural products including buttercup.
도 2는 미나리의 알코올 추출물을 다양한 용매로 다시 추출한 재분획 추출물의 아세틸콜린에스터라제 활성 억제율을 비교한 그래프이다.Figure 2 is a graph comparing the inhibition rate of acetylcholinesterase activity of the re-extracted extract extracted from the alcohol extract of buttercup with various solvents.
도 3은 논 미나리 추출물과 밭 미나리 추출물의 아세틸콜린에스터라제 활성 억제율을 비교한 그래프이다. Figure 3 is a graph comparing the inhibition rate of acetylcholinesterase activity of paddy field extract and field buttercup extract.
본 발명은 미나리에서 아세틸콜린에스터라제(AChE)의 활성 억제 및 학습능력 또는 기억력 증진에 효과가 있는 조성물을, 학습장애 또는 기억력 장애 예방 또는 치료용 약학 조성물이나 학습능력 또는 기억력 증진용 건강기능식품으로 활용하는 것이다.The present invention provides a composition that is effective in inhibiting the activity of acetylcholinesterase (AChE) and improving learning ability or memory in buttercups, a pharmaceutical composition for preventing or treating learning disorders or memory disorders, or health functional foods for improving learning ability or memory. Is to use.
본 발명에서 미나리는 미나리과 학명 움벨리퍼라세아에(Umbelliferaceae)에 속하는 오스테리쿰 코레아눔(Ostericum coreanum), 오에난테 스토니리페라(Oenanthe stonilifera), 오에난테 자바니카 (Oenanthe javanica) 등에 속하는 것으로, 바람직하게는 한국산 미나리이다.Buttercup in the present invention belongs to the asteraceae scientific name Umbelliferaceae ( Ostericum coreanum ), Oenanthe stonilifera ( Oenanthe stonilifera ), Oenanthe javanica ( Oenanthe javanica ), etc., preferably Crab is Korean parsley.
미나리는 통상 논에서 수경재배하는 물 미나리라고 불리우는 논 미나리와, 밭에서 재배하는 불 미나리라고 불리우는 밭 미나리 모두 사용될 수 있으나, 밭 미나리가 논 미나리에 비하여 아세틸콜린에스터라제(AChE)의 억제 활성이 뛰어나고, 약물에 의한 기억력 손상 예방 효과가 뛰어나다는 점에서 더욱 바람직하다.Buttercup can be used both as water parsley, which is usually hydroponicly grown in paddy fields, and field parsley, called fire parsley, which is grown in the field.However, the field buttercup has the inhibitory activity of acetylcholinesterase (AChE) compared to the paddy field. It is more preferable at the point that it is excellent and the effect of preventing memory damage by a drug is excellent.
본 발명의 미나리 추출물 제조를 위한 용매로 탄소수 1 내지 4의 저급 알코올, 또는 상기 저급 알코올의 수용액이 사용될 수 있다. 탄소수 1 내지 4의 저급 알코올로는 예를 들어 메탄올, 에탄올, 부탄올, 프로판올, 이소프로판올 등이 사용될 수 있고, 바람직하게는 에탄올을 사용한다.As a solvent for preparing the buttercup extract of the present invention, a lower alcohol having 1 to 4 carbon atoms, or an aqueous solution of the lower alcohol may be used. As the lower alcohol having 1 to 4 carbon atoms, for example, methanol, ethanol, butanol, propanol, isopropanol and the like can be used, and preferably ethanol is used.
또한 미나리 추출물 제조를 위한 용매로 알코올 수용액이 사용될 경우 물과 알코올이 혼합된 알코올 수용액에서 알코올의 혼합비율이 10 내지 95 (v/v)%인 알코올 수용액, 바람직하게는 20 내지 90 (v/v)%인 알코올 수용액, 보다 바람직하게는 50 내지 80(v/v)% 를 갖는 알코올 수용액이 사용된다.In addition, when the aqueous solution of alcohol is used as a solvent for preparing a buttercup extract, an aqueous solution of alcohol in which the mixing ratio of alcohol is 10 to 95 (v / v)% in an alcohol solution in which water and alcohol are mixed, preferably 20 to 90 (v / v). An aqueous aqueous solution of)%, more preferably an aqueous alcohol solution having 50 to 80 (v / v)% is used.
가장 바람직하게는 50 내지 80(v/v)% 를 갖는 에탄올 수용액으로 추출한 후, 그 추출액을 에틸아세테이트 또는 부탄올로 추출한 분획을 추출물로 사용하는 것이 아세틸콜린에스터라제(AChE)의 억제 활성이 뛰어나다는 점에서 유리하다.Most preferably, the extract is extracted with an aqueous ethanol solution having 50 to 80 (v / v)%, and the extract is extracted with ethyl acetate or butanol as an extract, which is excellent in inhibiting activity of acetylcholinesterase (AChE). It is advantageous in that.
본 발명의 미나리 추출물은 상기 용매를 사용하여 교반추출, 환류 냉각 추출, 냉침 추출, 초음파 추출 또는 초임계 추출 등의 추출방법으로 제조될 수 있고, Buttercup extract of the present invention may be prepared by an extraction method such as stirring extraction, reflux cooling extraction, cold needle extraction, ultrasonic extraction or supercritical extraction using the solvent,
특히 미나리에서 유효성분을 고농도로 효율적으로 추출하기 위해서는 건조 미나리 중량의 20 내지 200배, 바람직하게는 50 내지 150배의 탄소수 1 내지 4의 저급 알코올 수용액을 혼합하여 50 내지 90 ℃에서 4 내지 20 시간 추출하는 것이 바람직하다.In particular, in order to efficiently extract the active ingredient at high concentration in buttercup, 20 to 200 times the weight of dry buttercup, preferably 50 to 150 times by mixing a lower alcohol aqueous solution of 1 to 4 carbon atoms for 4 to 20 hours at 50 to 90 ℃ It is preferable to extract.
본 발명의 미나리 추출물을 유효성분으로 포함하는 조성물은 알츠하이머성 치매, 혈관성 치매, 기타 알콜 중독, 외상, 파킨슨병의 후유증으로 오는 치매나 인지 기능 장애의 예방 및 치료를 위해 사용될 수 있으며, 특히 알츠하이머성 치매의 치료에 적합하다.The composition comprising the buttercup extract of the present invention as an active ingredient can be used for the prevention and treatment of Alzheimer's dementia, vascular dementia, other alcoholism, trauma, Parkinson's disease, dementia or cognitive dysfunction, especially Alzheimer's disease. Suitable for the treatment of dementia.
본 발명의 조성물은, 조성물 총 중량에 대하여 미나리 추출물을 고형분 기준으로 0.1 내지 50% 중량으로 포함한다.The composition of the present invention includes the buttercup extract in an amount of 0.1 to 50% by weight based on the total weight of the composition.
그러나 상기와 같은 조성은 반드시 이에 한정되는 것은 아니고, 환자의 상태 및 질환의 종류 및 진행 정도에 따라 변할 수 있다.However, the composition as described above is not necessarily limited thereto, and may vary according to the condition of the patient and the type and extent of the disease.
본 발명의 미나리 추출물을 유효성분으로 포함하는 조성물은 약학적 조성물의 제조에 통상적으로 사용하는 적절한 담체, 부형제 및 희석제를 더 포함할 수 있다.The composition comprising the buttercup extract of the present invention as an active ingredient may further comprise suitable carriers, excipients and diluents commonly used in the manufacture of pharmaceutical compositions.
본 발명에 따른 미나리 추출물을 유효성분으로 포함하는 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 유효성분으로 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.Compositions comprising the buttercup extract according to the present invention as an active ingredient, oral formulations, such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, external preparations, suppositories, and sterile injectable solutions, respectively, according to conventional methods Carriers, excipients and diluents which may be used in the form of a formulation, which may be included in the composition containing the extract as an active ingredient, 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 Can be mentioned. When formulated, diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrating agents, and surfactants are usually used.
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.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.
본 발명의 조성물의 바람직한 투여량은 환자의 상태 및 체중, 질병의 정도, 약물형태, 투여경로 및 기간에 따라 다르지만, 당업자에 의해 적절하게 선택될 수 있다. 그러나 바람직한 효과를 위해서, 본 발명의 조성물은 미나리 추출물의 고형분을 기준으로 1일 0.01 mg/kg 내지 10 g/kg으로, 바람직하게는 1 mg/kg 내지 1 g/kg으로 투여하는 것이 좋다. 투여는 하루에 한번 투여할 수도 있고, 수회 나누어 투여할 수 있다. 따라서, 상기 투여량은 어떠한 면으로든 본 발명의 범위를 한정하는 것은 아니다.Preferred dosages of the compositions of the present invention vary depending on the condition and weight of the patient, the extent of the disease, the form of the drug, the route of administration and the duration, and may be appropriately selected by those skilled in the art. However, for the desired effect, the composition of the present invention is preferably administered at 0.01 mg / kg to 10 g / kg, preferably 1 mg / kg to 1 g / kg based on the solid content of the buttercup extract. Administration may be administered once a day or may be divided several times. Therefore, the above dosage does not limit the scope of the present invention in any aspect.
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. 특히 바람직하게는 본 발명의 미나리 추출물은 경구 투여시 복강 투여에 비하여 기억력 손상 예방 효과가 뛰어나다.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. Especially preferably, the buttercup extract of the present invention is superior in preventing memory damage compared to intraperitoneal administration.
본 발명은 학습능력 또는 기억력 증진 효과를 나타내는 미나리 추출물 및 식품학적으로 허용 가능한 식품보조 첨가제를 포함하는 건강기능식품을 제공한다.The present invention provides a dietary supplement comprising a buttercup extract and a food supplement acceptable food supplement additive exhibiting a learning or memory enhancing effect.
본 발명의 미나리 추출물을 유효성분으로 포함하는 조성물은 식품으로는, 예를 들어, 각종 식품류, 음료, 껌, 차, 비타민 복합제, 건강보조 식품류 등이 있고, 분말, 과립, 정제, 캡슐 또는 음료인 형태로 사용할 수 있다.The composition comprising the buttercup extract of the present invention as an active ingredient includes, for example, various foods, beverages, gums, teas, vitamin complexes, health supplements, and the like, and are powders, granules, tablets, capsules, or beverages. Available in form.
본 발명의 미나리 추출물 자체는 독성 및 부작용은 거의 없으므로 예방 목적으로 장기간 복용 시에도 안심하고 사용할 수 있는 약제이다. Buttercup extract itself of the present invention is a drug that can be used with confidence even when taken for a long time for the purpose of prevention because there is little toxicity and side effects.
본 발명의 상기 미나리 추출물은 학습능력 또는 기억력 증진 효과를 위하여 건강기능식품에 첨가될 때, 상기 추출물의 양은 고형분을 기준으로 일반적으로 본 발명의 분말, 과립, 정제, 캡슐 등의 형태의 건강기능식품인 경우 전체 식품 중량의 0.01 내지 15 중량%로 가할 수 있으며, 음료 형태의 건강기능식품인 경우 음료 100 ㎖를 기준으로 0.02 내지 10 g, 바람직하게는 0.3 내지 1 g의 비율로 가할 수 있다. When the buttercup extract of the present invention is added to a health functional food for learning or memory enhancing effect, the amount of the extract is generally based on solids, health functional food in the form of powder, granules, tablets, capsules, etc. of the present invention. In the case of can be added in an amount of 0.01 to 15% by weight of the total food weight, in the case of a health functional food in the form of a beverage can be added in a ratio of 0.02 to 10 g, preferably 0.3 to 1 g based on 100 ml of the beverage.
본 발명의 음료 형태의 건강기능식품은 지시된 비율로 필수 성분으로서 상기 추출물을 함유하는 것 외에 액체성분에는 특별한 제한점은 없으며 통상의 음료와 같이 여러 가지 향미제 또는 천연 탄수화물 등을 추가 성분으로서 함유할 수 있다. 상술한 천연 탄수화물의 예는 모노사카라이드, 예를 들어, 포도당, 과당 등의 디사카라이드, 예를 들어 말토스, 슈크로스 등의 및 폴리사카라이드, 예를 들어 덱스트린, 시클로덱스트린 등과 같은 통상적인 당 및 자일리톨, 소르비톨, 에리트리톨 등의 당알콜이다. 상술한 것 이외의 향미제로서 천연 향미제(타우마틴, 스테비아 추출물(예를 들어 레바우디오시드 A, 글리시르히진등) 및 합성 향미제(사카린, 아스파르탐 등)를 유리하게 사용할 수 있다. 상기 천연 탄수화물의 비율은 본 발명의 조성물 100 ㎖당 일반적으로 약 1 내지 20g, 바람직하게는 약 5 내지 12g이다.The health functional food of the beverage form of the present invention contains the extract as an essential ingredient in the ratio indicated, and there are no special limitations in the liquid component, and it may contain various flavors or natural carbohydrates as additional ingredients, such as ordinary drinks. Can be. Examples of the above-mentioned natural carbohydrates are conventional monosaccharides such as disaccharides such as glucose and fructose, such as maltose, sucrose and the like, and polysaccharides such as dextrin, cyclodextrin and the like. Sugars and sugar alcohols such as xylitol, sorbitol, and erythritol. As flavoring agents other than those mentioned above, natural flavoring agents (tauumatin, stevia extract (for example, rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.) can be advantageously used. The proportion of natural carbohydrates is generally about 1-20 g, preferably about 5-12 g per 100 ml of the composition of the present invention.
상기 외에 본 발명의 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, 알콜, 탄산 음료에 사용되는 탄산화제 등을 함유할 수 있다. 그밖에 본 발명의 조성물들은 천연 과일 쥬스 및 과일 쥬스 음료 및 야채 음료의 제조를 위한 과육을 함유할 수 있다. 이러한 성분은 독립적으로 또는 조합하여 사용할 수 있다. 이러한 첨가제의 비율은 그렇게 중요하진 않지만 본 발명의 조성물 100 중량부 당 0 내지 약 20 중량부의 범위에서 선택되는 것이 일반적이다.In addition to the above, the composition of the present invention includes various nutrients, vitamins, minerals (electrolytes), flavors such as synthetic flavors and natural flavors, coloring and neutralizing agents (such as cheese and chocolate), pectic acid and salts thereof, alginic acid and its Salts, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohols, carbonation agents used in carbonated beverages, and the like. The compositions of the present invention may also contain pulp for the production of natural fruit juices and fruit juice beverages and vegetable beverages. These components can be used independently or in combination. The proportion of such additives is not so critical but is generally selected from the range of 0 to about 20 parts by weight per 100 parts by weight of the composition of the present invention.
이하, 본 발명을 실시예 및 실험예에 의해 상세히 설명한다. Hereinafter, the present invention will be described in detail by Examples and Experimental Examples.
단, 하기 실시예 및 실험예는 본 발명을 예시하는 것일 뿐, 본 발명의 내용이 이에 한정되는 것은 아니다. However, the following Examples and Experimental Examples are merely illustrative of the present invention, but the content of the present invention is not limited thereto.
실험예 1 : 각종 천연물의 아세틸콜린에스터라제(AChE)의 억제활성 비교 (Ellman's method)Experimental Example 1 Comparison of Inhibitory Activity of Acetylcholinesterase (AChE) from Various Natural Products (Ellman's Method)
백년초 열매, 석류, 유자, 무화과, 신선초, 대추 및 논 미나리 70 (v/v)%의 에탄올 수용액 추출물을 제조하여 아세틸콜린에스터라제 억제활성을 비교하였다. Extracts of ethanol aqueous solution of baeknyeon fruit, pomegranate, citron, fig, fresh vinegar, jujube and paddy parsley 70 (v / v)% were prepared to compare the inhibitory activity of acetylcholinesterase.
각각의 에탄올 수용액 추출물은 건조 시료 10 g에 주정(에탄올 함량 70 (v/v)%) 600 ㎖를 넣고 60 ℃에서 8시간 환류시키지 않고 추출하고, 여과하여 잔사를 제거한 후 50 내지 60 mmHg 및 30 내지 40 ℃의 조건하에서 증발농축하였고, 그 결과로 얻어진 농축액을 열풍건조하여 에탄올 추출물 분말을 얻었다.Each ethanol aqueous solution extract was extracted with 10 ml of dry sample 600 ml of ethanol (ethanol content 70 (v / v)%) without reflux at 60 ℃ for 8 hours, filtered to remove the residue 50 to 60 mmHg and 30 The resultant was evaporated to concentration under the condition of 40 to 40 ° C., and the resultant concentrate was hot-air dried to obtain an ethanol extract powder.
상기 각각의 에탄올 추출물 분말을 디메틸술폭사이드(DMSO)에 용해시킨 후 100 mM 인산염(pH 8.0, "완충액 I"이라 함)에 1000 ㎍/㎖ 농도로 희석하였다(DMSO의 경우 최종농도 10%로 희석). 상기 완충액 I에 희석된 추출물 분말 1.5 ㎖, 100 mM 인산염(pH 7.0, "완충액 Ⅱ"라 함) 1.5 ㎖, 75 mM 아세틸티오콜린요오드 용액 20 ㎕ 및 완충엘만시약[Buffered Ellman's reagent; 5,5'-디티오-비스(2-니트로벤조산)10 mM, NaHCO3 17.85 mM] 100 ㎕를 혼합하고 25 ℃에서 10 분간 정체시켰다. 그리고, AChE 효소(20 ㎕)를 넣고 흔들어 섞어준 다음 30초 간격으로 5 분동안 흡광도를 측정하므로써 선형반응(linear reaction)임을 확인하였다.Each of the ethanol extract powder was dissolved in dimethyl sulfoxide (DMSO) and then diluted in 100 mM phosphate (pH 8.0, referred to as "buffer I") at a concentration of 1000 μg / ml (for DMSO, diluted to a final concentration of 10%). ). 1.5 ml of extract powder diluted in Buffer I, 1.5 ml of 100 mM phosphate (pH 7.0, referred to as "Buffer II"), 20 µl of 75 mM acetylthiocholine iodine solution and Buffered Ellman's reagent; 10 μl of 5,5′-dithio-bis (2-nitrobenzoic acid), NaHCO 3 17.85 mM] was mixed and allowed to stand at 25 ° C. for 10 minutes. Then, the mixture was shaken and mixed with AChE enzyme (20 μl), and the linear reaction was confirmed by measuring absorbance for 5 minutes at 30 second intervals.
블랭크(blank)에는 효소 대신 식염수(saline)를 넣어주었다. 또한, 아세틸티오콜린요오드 용액을 넣지 않고 흡광도를 측정하여 에탄올 추출물 분말과 효소활성측정시 약간의 비특이적 반응이 나타나지 않음도 확인하였다. Blank was added with saline instead of enzyme. In addition, by measuring the absorbance without the addition of acetylthiocholine iodine solution, it was also confirmed that a slight non-specific reaction does not appear when measuring the ethanol extract powder and enzyme activity.
또한, 추출물을 넣지 않았을 때를 음성대조군으로 하고 이때의 AChE 활성도를 100%로 하였을 때, 각 식물의 에탄올 추출물(500 ㎍/㎖)에 대한 AChE 억제활성도를 '%억제'로 도 1에 나타내었다. AChE 활성실험은 5회 반복하여 결과의 유의성을 one-way ANOVA 테스트로 검정하였다.In addition, when the extract was not added as a negative control group and the AChE activity at this time to 100%, the AChE inhibitory activity against the ethanol extract (500 ㎍ / ㎖) of each plant is shown in Figure 1 as '% inhibition'. . The AChE activity experiment was repeated five times to test the significance of the results by a one-way ANOVA test.
도 1에 따르면, 백년초 열매, 석류 및 유자 추출물에서 8 내지 11 %의 아세틸콜린에스터라제 활성 억제율을 나타내었으나, 논 미나리 추출물에서는 2 배 이상인 23.5 %의 활성 억제율을 나타내었고, 무화과, 신선초 및 대추 추출물의 효소 활성 억제율은 5 % 미만으로 미미하였다.According to Figure 1, baeknyeoncho fruit, pomegranate and citron extract showed 8 to 11% inhibition of acetylcholinesterase activity, but the non-parsley extract exhibited an activity inhibition rate of 23.5%, more than 2 times, fig, fresh vinegar and jujube Inhibition rate of the enzyme activity of the extract was less than 5%.
실험예 2 : 미나리 추출방법에 따른 아세틸콜린에스터라제(AChE)의 억제활성 비교Experimental Example 2 Comparison of Inhibitory Activity of Acetylcholinesterase (AChE) According to the Extract of Buttercup
건조 논 미나리 10 g에 정제수 600 ㎖를 넣고 100 ℃에서 8시간 열수추출하고, 여과하여 잔사를 제거한 후 50 내지 60 mmHg 및 30 내지 40 ℃의 조건하에서 증발농축하였고, 그 결과로 얻어진 농축액을 열풍건조하여 열수추출물 분말을 얻었다.600 g of purified water was added to 10 g of dried paddy field, hot water extracted at 100 ° C. for 8 hours, filtered to remove the residue, and the resultant was evaporated and concentrated under the conditions of 50 to 60 mmHg and 30 to 40 ° C., and the resultant concentrate was hot-air dried. To obtain a hot water extract powder.
또한 건조 논 미나리 10 g에 주정(에탄올 함량 75 (v/v)%) 600 ㎖를 넣고 60 ℃에서 8시간 환류시키지 않고 추출하고, 여과하여 잔사를 제거한 후 50 내지 60 mmHg 및 30 내지 40 ℃의 조건하에서 증발농축하였고, 그 결과로 얻어진 농축액을 열풍건조하여 알코올 추출물 분말을 얻었다.In addition, 600 g of alcohol (ethanol content 75 (v / v)%) was added to 10 g of dried rice buttercups, extracted without refluxing at 60 ° C. for 8 hours, and filtered to remove the residue, followed by 50 to 60 mmHg and 30 to 40 ° C. Evaporation was carried out under the conditions, and the resultant concentrate was hot-air dried to obtain an alcohol extract powder.
상기 논 미나리 열수추출물 분말과 알코올 추출물 분말의 아세틸콜린에스터라제 활성 억제율을 실험예 1의 방법으로 측정하였고, 양성대조군으로 DHED를 37.8 μM이 되도록 첨가하여 비교하였으며, 그 결과를 표 1에 나타내었다. AChE 활성실험은 5회 반복하여 결과의 유의성을 one-way ANOVA 테스트로 검정하였다.The inhibition rate of acetylcholinesterase activity of the non-parsley hot water extract powder and the alcohol extract powder was measured by the method of Experimental Example 1, and compared with DHED added to 37.8 μM as a positive control group, the results are shown in Table 1. . The AChE activity experiment was repeated five times to test the significance of the results by a one-way ANOVA test.
표 1
구분 농도 AChE 억제활성도(%)
양성대조군(DHED) 37.8 μM 45.2±5.2
열수추출물 분말 500㎍/㎖ 2.4±0.4
알코올추출물 분말 500㎍/㎖ 31.5±9.6
Table 1
division density AChE inhibitory activity (%)
Positive control group (DHED) 37.8 μM 45.2 ± 5.2
Hot Water Extract Powder 500 µg / ml 2.4 ± 0.4
Alcohol extract powder 500 µg / ml 31.5 ± 9.6
실험예 3 : 미나리 추출물의 분획방법에 따른 아세틸콜린에스터라제(AChE)의 억제활성 비교Experimental Example 3 Comparison of Inhibitory Activity of Acetylcholinesterase (AChE) According to the Fractionation Method of Buttercup Extract
실험예 2의 건조 논 미나리 10 g에 주정(에탄올 함량 75 (v/v)%) 600 ㎖를 넣고 60 ℃에서 8시간 환류시키지 않고 추출하고, 여과하여 잔사를 제거한 후, 각각 헥산, 클로로포름, 에틸아세테이트, 부탄올 및 물로 추출하여 각각의 분획 추출물을 얻고, 이들 각각을 50 내지 60 mmHg 및 30 내지 40 ℃의 조건하에서 증발농축하였고, 그 결과로 얻어진 농축액을 열풍건조하여 추출물 분말을 얻었다.600 ml of alcohol (ethanol content 75 (v / v)%) was added to 10 g of dried paddy butter of Experimental Example 2, extracted without reflux at 60 ° C for 8 hours, filtered to remove the residue, and then hexane, chloroform and ethyl, respectively. Extraction with acetate, butanol and water yielded respective fractional extracts, each of which was evaporated to concentration under conditions of 50 to 60 mmHg and 30 to 40 ° C., and the resulting concentrate was hot-air dried to obtain an extract powder.
각각의 분획 추출물(500 ㎍/㎖)의 아세틸콜린에스터라제 활성 억제율을 실험예 1의 방법으로 측정하여 도 2에 나타내었다. 각각의 분획 추출물 중, 에틸아세테이트와 부탄올 추출물의 효소 활성 억제율이 가장 크게 나타나, E알코올 추출에 의한 미나리 추출물의 아세틸콜린에스터라제 활성을 억제하는 유효성분은 에틸아세테이트층 또는 부탄올층에 있을 것으로 판단되었다.The inhibition rate of acetylcholinesterase activity of each fraction extract (500 μg / ml) was measured by the method of Experimental Example 1 and is shown in FIG. 2. Among the fraction extracts, ethyl acetate and butanol extract showed the greatest inhibition rate of enzyme activity, and the active ingredient which inhibits acetylcholinesterase activity of the buttercup extract by E-alcohol extraction was considered to be in ethyl acetate layer or butanol layer. It became.
실험예 4 : 논 미나리와 밭 미나리의 아세틸콜린에스터라제(AChE)의 억제활성 비교Experimental Example 4: Comparison of the Inhibitory Activity of Acetylcholinesterase (AChE) in Paddy Fields
실험예 2의 논 미나리 대신에 건조 밭 미나리 10 g에 주정(에탄올 함량 75 (v/v)%) 600 ㎖를 넣고 60 ℃에서 8시간 환류시키지 않고 추출하고, 여과하여 잔사를 제거한 후, 50 내지 60 mmHg 및 30 내지 40 ℃의 조건하에서 증발농축하였고, 그 결과로 얻어진 농축액을 열풍건조하여 추출물 분말을 얻었다.600 ml of spirits (ethanol content 75 (v / v)%) was added to 10 g of dry field buttercups instead of the rice buttercups of Experimental Example 2, extracted without refluxing at 60 ° C. for 8 hours, and filtered to remove residues. Evaporation was carried out under the conditions of 60 mmHg and 30-40 degreeC, and the resulting concentrate was hot-air dried to obtain an extract powder.
논 미나리 추출물 분말 및 밭 미나리 추출물 분말은 500 ㎍/㎖ 농도로, 양성대조군으로 DHED는 100 μM 농도로 첨가하여 실험예 1의 방법으로 아세틸콜린에스터라제 활성 억제율을 측정하여 도 3에 나타내었다.Non- buttercup extract powder and field buttercup extract powder were added at a concentration of 500 μg / ml, DHED was added at a concentration of 100 μM as a positive control group, and the inhibition rate of acetylcholinesterase activity was measured by the method of Experimental Example 1 and is shown in FIG. 3.
밭 미나리 추출물은 동일한 추출 방법으로 제조되고, 동일 농도가 사용되었음에도 논 미나리 추출물의 효소 활성 억제율에 비해 2 배 이상 높아진 것을 확인할 수 있었고, 50 μM 농도의 DHED와 동등한 수준의 효소 활성 억제율을 나타내었다.The field buttercup extract was prepared by the same extraction method, and even though the same concentration was used, it was confirmed that it was more than two times higher than the inhibition rate of the enzyme activity of the non buttercup extract, and showed the same level of inhibition of enzyme activity as the DHED of 50 μM.
실험예 5 : 수동회피반응에 의한 학습장애 및 기억력 장애 예방 효과 확인Experimental Example 5: Confirmation of prevention of learning disorders and memory disorders by passive avoidance reaction
실험기구로는 Shuttle box (50×15×40 cm)로 바닥은 electric grid floor이다. 상자는 칸막이문으로 나누어져 25×15 cm의 방을 이루고 있다. 이 실험은 소음이 60dB 이하이고, 조명을 어둡게 한 방에서, 랫트의 스코폴라민(scopolamine)에 의해 손상된 학습과 기억력 손상이 실험예 4의 논 미나리 추출물 및 밭 미나리 추출물 투여를 통해 치료될 수 있는지 살펴보았다.The experimental instrument is a shuttle box (50 × 15 × 40 cm) with an electric grid floor. The box is divided into partition doors and forms a room of 25 × 15 cm. In this experiment, noise and noise of 60 dB or less, and whether the learning and memory impairment impaired by scopolamine in rats can be treated through the administration of Paddy Buttercup and Field Buttercup extract of Experiment 4 I looked at it.
실험 첫날 실험대상이 되는 모든 동물들에 대해 다음과 같은 실험을 동일하게 실시하였다. 칸막이로 나누어진 방 2개 중 밝은 방에 랫트를 넣고 1500 lux의 조명을 켜면서 칸막이를 열어준다. 랫트는 방안을 여기저기 살피다가 조명이 없는 건너편 어두운 방으로 들어가게 되는데, 이때 자동적으로 칸막이가 닫히게 된다. 불을 켜면서 칸막이가 열릴 때부터 칸막이가 닫힐 때까지 latency를 측정하는데, 이러한 trial을 3-4 회 반복하면 4회째는 거의 예외 없이 20초 안에 밝은 방에서 어두운 방으로 넘어간다. On the first day of the experiment, the following experiments were performed on all the animals to be tested. The rat is placed in a bright room out of the two divided rooms, and the compartment is opened while lighting at 1500 lux. The rat looks around the room and enters a dark room across the street with no lighting, which automatically closes the partition. With the lights on, latency is measured from the opening of the partition to the closing of the partition. Repeating these trials 3-4 times, the fourth pass from the bright room to the dark room in almost 20 seconds with almost no exception.
실험 둘째날 체중 200 내지 250 g 랫트에 실험예 4의 논 미나리 추출물 분말 및 밭 미나리 추출물 분말을 각각 10 mg/kg 씩 경구 투여하고, 양성대조군인 Tacrine은 1 mg/kg로 경구 투여하였다.On the second day of the experiment, 200 mg to 250 g rats were orally administered with 10 mg / kg of the field of Buttercup extract powder and field buttercup extract powder of Experiment 4, respectively, and the positive control Tacrine was orally administered at 1 mg / kg.
추출물 및 Tacrine 투여 1시간 후, 생리식염수에 녹인 scopolamine을 4.5 mg/kg로 복강내로 투여하고, 다시 1시간 후 shuttle box에서 다음과 같이 foot-shock을 주었다. 랫트가 밝은 방에서 어두운 방으로 넘어가면 불이 꺼진 상태에서 0.3 mA의 전류를 방밑의 stainless grid를 통해 3초 동안 흘려 랫트에게 foot-shock을 주었다. 랫트는 어두운 방과 foot-shock과의 관계를 기억하게 되며, 20시간 후 밝은 방에 넣어주면, 조명이 들어와도 어두운 방에 들어가기를 망설이게 된다. 이 때의 latency를 각 그룹별로 비교하여 표 2에 나타내었다.After 1 hour of extract and Tacrine administration, scopolamine dissolved in physiological saline was administered intraperitoneally at 4.5 mg / kg, and after 1 hour, foot-shock was given in the shuttle box as follows. When the rat passed from a bright room to a dark room, the rats were foot-shocked by flowing 0.3 mA of current through the stainless grid under the room for 3 seconds. The rat will remember the relationship between the dark room and the foot-shock, and if he puts it in the bright room after 20 hours, he will hesitate to enter the dark room even if the lights come on. The latency at this time is compared to each group and is shown in Table 2.
표 2
구분 Latency time(초)
대조군(스코폴라민 비투여군) 260±39.6
스코폴라민 투여군 17±5.4
타크린 투여후 스코폴라민 투여군 32±13.4
논 미나리 투여후 스코폴라민 투여군 17±5.1
밭 미나리 투여후 스코폴라민 투여군 44±7.2
TABLE 2
division Latency time (seconds)
Control group (Scopolamine non-administered group) 260 ± 39.6
Scopolamine Administration Group 17 ± 5.4
Scopolamine-treated group after tacrine administration 32 ± 13.4
Scopolamine-treated group after non-minari 17 ± 5.1
Scopolamine-treated group after field buttercup administration 44 ± 7.2
대조군에 비해 스코폴라민 투여군의 기억력 저하가 뚜렷하게 보였다. 이렇게 스코폴라민에 의해 저하된 기억력은 항콜린에스터라아제이면서 기존에 치매약물로 사용되었던 tacrine에 의해 회복되었다. 또한 스코폴라민에 의해 저하된 기억력의 회복은 논 미나리보다 밭 미나리에서 효과가 더 크게 나타났으며, 밭 미나리의 기억력 회복 효과는 타크린에 비하여 더 우수하였다.Compared with the control group, the memory loss of the scopolamine-administered group was obvious. The memory reduced by scopolamine was restored by tacrine, an anticholinesterase that was previously used as a dementia drug. In addition, the recovery of memory lowered by scopolamine was more effective in the field buttercups than in the field buttercups, and the memory recovery effect of the field buttercups was better than that of tacrine.
이러한 밭 미나리의 기억력 회복 효과가 경구 투여는 물론 복강 투여에서도 동일하게 나타나는지를 확인하기 위하여, 동일 용량의 밭 미나리 추출물 분말을 동일 농도로 희석하여 상기 방법에서 투여 경로만 변경하여 다시 실험하여 그 결과를 표 3에 나타내었다.In order to confirm whether the memory recovery effect of the garden parsley is the same in oral administration as well as intraperitoneal administration, dilute the same dose of parsley extract powder to the same concentration, change the administration route in the above method, and test the results again. Table 3 shows.
표 3
구분 Latency time(초)
스코폴라민 투여군 17±5.4
밭 미나리 경구 투여후 스코폴라민 투여군 44±7.2
밭 미나리 복강 투여후 스코폴라민 투여군 14±3.6
TABLE 3
division Latency time (seconds)
Scopolamine Administration Group 17 ± 5.4
Scopolamine-treated group after oral administration of field buttercup 44 ± 7.2
Scopolamine-treated group after field parsley intraperitoneal administration 14 ± 3.6
스코폴라민 투여로 인한 기억력 저하의 회복에 대하여 밭 미나리 추출물을 경구 투여했을 때에는 스코폴라민 투여군에 비하여 Latency time이 2.6 배 증진되었으나, 복강 투여에서는 기억력 저하의 회복 효과를 확인할 수 없었다.The oral administration of the field parsley extract improved 2.6 times the latency time compared to the scopolamine-treated group. However, intraperitoneal administration did not confirm the recovery of memory-lowering memory.
실험예 6 : 알코올에 의한 기억력 저하의 치료 효과 확인Experimental Example 6: Confirmation of the therapeutic effect of memory degradation caused by alcohol
알코올에 의한 기억력 저하의 치료 효과를 4 주간 실시하였다. 알코올은 2.5 g/kg 용량으로 매일 복강 투여하였다. 밭 미나리 추출물의 투여용량은 10 mg/kg 및 양성대조군인 linoleic acid은 10 mg/kg로 4주간 경구투여하였다. 4주간 투여 후에 Y-미로 테스트를 수행하였다. The therapeutic effect of memory-lowering memory was carried out for 4 weeks. Alcohol was intraperitoneally administered at a 2.5 g / kg dose daily. Doses of field buttercup extract were orally administered at 10 mg / kg and the positive control linoleic acid at 10 mg / kg for 4 weeks. The Y-maze test was performed after 4 weeks of administration.
Y-미로 테스트는 공간지각을 검증하는 테스트 방법으로, 크기가 동일한 세개의 arms으로 구성되며 검정색 plastic 미로이다. 각각의 arm은 80×35×15 cm로 구성되며 각 arm은 동일한 각도를 유지한다. 랫트는 arm의 끝에 놓고 자유롭게 10 분간 이동할 수 있게 한다. 랫트가 각 arm에 들어가는 순서를 기록한다. 각기 다른 세 개의 arms을 연속적으로 선택할 때 점수를 준다. 이들 점수 (% of alternation)를 그룹별로 비교하여 표 4에 나타내었다.The Y-maze test is a test method for verifying spatial perception, consisting of three arms of the same size and a black plastic maze. Each arm consists of 80 × 35 × 15 cm and each arm maintains the same angle. The rat is placed at the end of the arm and allowed to move freely for 10 minutes. Record the order in which the rat enters each arm. Scores are given when three different arms are selected in succession. These scores (% of alternation) are shown in Table 4 by comparing the groups.
표 4
구분 % of alteration
대조군 66.8±3.5
대조군에 밭 미나리 추출물 경구투여 62.0±5.7
알코올 복강투여 42.9±5.2
알코올 복강투여 및 리놀레산 경구투여 62.3±2.8
알코올 복강투여 및 밭 미나리 추출물 경구투여 62.2±4.6
Table 4
division % of alteration
Control 66.8 ± 3.5
Oral administration of field buttercup extract to control group 62.0 ± 5.7
Alcohol intraperitoneal administration 42.9 ± 5.2
Alcohol intraperitoneal administration and linoleic acid oral administration 62.3 ± 2.8
Alcohol intraperitoneal administration and field buttercup extract oral administration 62.2 ± 4.6
대조군에 알코올을 4주 동안 복강투여 함으로써 기억력 저하가 대조군에 비하여 기억력 저하가 뚜렷하게 나타났다. 이렇게 알코올에 의해 저하된 기억력은 종래 기억력 개선 효과가 알려진 리놀레산의 투여에 의하여 회복되었고, 본 발명의 밭 미나리 추출물을 경구 투여했을 때에도 리놀레산과 동등한 수준의 알코올에 의한 기억력 손상 회복 효과를 나타내었다.By intraperitoneal administration of alcohol to the control group for 4 weeks, memory loss was significantly lower than that of the control group. Thus, the memory reduced by alcohol was recovered by the administration of linoleic acid known to improve the conventional memory, and even when oral administration of the field buttercup extract of the present invention showed a recovery effect of memory damage by the same level of alcohol with linoleic acid.
실험예 7 : 스트레스에 의한 기억력 손상의 치료 효과 확인Experimental Example 7: Confirm the therapeutic effect of memory impairment caused by stress
스트레스에 의한 기억력 저하의 치료 효과를 4 주간 실시하였다. 스트레스 실험을 위해 랫트를 매일 6시간 동안 plastic box에서 움직이지 못하게 하는 고정스트레스를 주었다. 밭 미나리 추출물의 투여용량은 10 mg/kg 및 양성대조군인 linoleic acid은 10 mg/kg로 4주간 경구투여하였다. 4주간 투여 후에 실험예 6과 동일한 방법으로 Y-미로 테스트를 수행하여 그 결과를 표 5에 나타내었다.The treatment effect of memory lowering due to stress was performed for 4 weeks. For stress experiments, rats were given a fixed stress that prevented them from moving in a plastic box for 6 hours each day. Doses of field buttercup extract were orally administered at 10 mg / kg and the positive control linoleic acid at 10 mg / kg for 4 weeks. After four weeks of administration, the Y-maze test was performed in the same manner as in Experimental Example 6, and the results are shown in Table 5.
표 5
구분 % of alteration
대조군 68.24±4.32
대조군에 밭 미나리 추출물 경구투여 72.54±6.21
스트레스군 60.13±5.17
스트레스군에 리놀레산 경구투여 67.53±4.94
스트레스군에 밭 미나리 추출물 경구투여 69.09±4.52
Table 5
division % of alteration
Control 68.24 ± 4.32
Oral administration of field buttercup extract to control group 72.54 ± 6.21
Stress group 60.13 ± 5.17
Linoleic acid oral administration to stress group 67.53 ± 4.94
Oral administration of field buttercup extract to stress group 69.09 ± 4.52
랫트에 스트레스를 줌으로써 기억력 저하가 대조군에 비하여 기억력 저하가 뚜렷하게 나타났다. 이렇게 스트레스에 의해 저하된 기억력은 종래 기억력 개선 효과가 알려진 리놀레산의 투여에 의하여 회복되었고, 본 발명의 밭 미나리 추출물을 경구 투여했을 때에도 리놀레산과 동등한 수준의 알코올에 의한 기억력 손상 회복 효과를 나타내었다.By stressing the rats, memory loss was significantly lower than that of the control group. Thus, the memory reduced by stress was recovered by administration of linoleic acid, which is known to improve the conventional memory, and even when oral administration of the field buttercup extract of the present invention showed an effect of recovering memory damage by alcohol equivalent to linoleic acid.
하기에 본 발명의 추출물을 함유하는 조성물의 제제예를 설명하나, 본 발명은 이를 한정하고자 함이 아닌 단지 구체적으로 설명하고자 함이다.Hereinafter, a preparation example of a composition containing an extract of the present invention will be described, but the present invention is not intended to be limited thereto but only to be described in detail.
제제예 1. 산제의 제조Formulation Example 1 Preparation of Powder
실험예 4에서 얻은 밭 미나리 추출물 분말 20 mg20 mg of field buttercup extract powder obtained in Experiment 4
유당 100 mgLactose 100 mg
탈크 10 mg Talc 10 mg
상기의 성분들을 혼합하고 기밀포에 충진하여 산제를 제조한다.The above ingredients are mixed and filled in an airtight cloth to prepare a powder.
제제예 2. 정제의 제조Formulation Example 2 Preparation of Tablet
실험예 4에서 얻은 밭 미나리 추출물 분말 10 mg10 mg of field buttercup extract powder obtained in Experiment 4
옥수수전분 100 mgCorn starch 100 mg
유당 100 mgLactose 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
실험예 4에서 얻은 밭 미나리 추출물 분말 10 mg10 mg of field buttercup extract powder obtained in Experiment 4
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.
제제예 4. 주사제의 제조Formulation Example 4 Preparation of Injection
실험예 4에서 얻은 밭 미나리 추출물 분말 10 mg10 mg of field buttercup extract powder obtained in Experiment 4
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 앰플 당(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
실험예 4에서 얻은 밭 미나리 추출물 분말 20 mg20 mg of field buttercup extract powder obtained in Experiment 4
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 레몬향을 적량 가한 다음 상기의 성분을 혼합한 다음 정제수를 가하여 전체를 정제수를 가하여 전체 100㎖로 조절한 후 갈색병에 충진하여 멸균시켜 액제를 제조한다.According to the conventional method of preparing a liquid solution, each component is added and dissolved in purified water, lemon flavor is added to the mixture, and then the above ingredients are mixed, purified water is added to adjust the total amount to 100 ml, and then filled in a brown bottle. The solution is prepared by sterilization.
제제예 6. 건강 식품의 제조Formulation Example 6 Preparation of Healthy Food
실험예 4에서 얻은 밭 미나리 추출물 분말 1,000 ㎎1,000 mg of field buttercup extract powder obtained in Experimental Example 4
비타민 혼합물 적량Vitamin Mixture
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 vitamin and mineral mixture is a composition suitable for a relatively healthy 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 제조Formulation Example 7 Preparation of Healthy Drink
실험예 4에서 얻은 밭 미나리 추출물 분말 1,000 ㎎1,000 mg of field buttercup extract powder obtained in Experimental Example 4
구연산 1,000 ㎎Citric Acid 1,000 mg
올리고당 100 g100 g oligosaccharides
매실농축액 2 gPlum concentrate 2 g
타우린 1 g1 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, 수요국가, 사용용도 등 지역적, 민족적 기호도에 따라서 그 배합비를 임의로 변형 실시하여도 무방하다.Although the composition ratio is a composition that is relatively suitable for the preferred beverage in a preferred embodiment, the composition ratio may be arbitrarily modified according to regional and ethnic preferences such as demand hierarchy, demand country, and usage.

Claims (10)

  1. 미나리 추출물을 유효성분으로 하는 학습장애 또는 기억력 장애 예방 또는 치료용 약학 조성물.A pharmaceutical composition for preventing or treating learning disorders or memory disorders comprising the buttercup extract as an active ingredient.
  2. 제 1 항에 있어서, 상기 미나리는 밭 미나리인 것을 특징으로 하는 학습장애 또는 기억력 장애 예방 또는 치료용 약학 조성물.The pharmaceutical composition for preventing or treating learning disorders or memory disorders of claim 1, wherein the buttercups are field buttercups.
  3. 제 1 항 또는 제 2 항에 있어서, 경구 투여용인 것을 특징으로 하는 학습장애 또는 기억력 장애 예방 또는 치료용 약학 조성물.The pharmaceutical composition for preventing or treating learning disorders or memory disorders according to claim 1 or 2, which is for oral administration.
  4. 제 1 항 또는 제 2 항에 있어서, 상기 추출물은 탄소수 1 내지 4의 저급 알코올, 또는 상기 저급 알코올의 수용액으로로부터 선택된 용매에 가용한 추출물인 것을 특징으로 하는 학습장애 또는 기억력 장애 예방 또는 치료용 약학 조성물.The method of claim 1 or 2, wherein the extract is a lower alcohol having 1 to 4 carbon atoms, or an extract available in a solvent selected from an aqueous solution of the lower alcohol, characterized in that for preventing or treating learning disorders or memory disorders Composition.
  5. 제 4 항에 있어서, 상기 알코올 수용액은 저급 알코올의 혼합비가 10 내지 95(v/v)%인 알코올 수용액임을 특징으로 하는 학습장애 또는 기억력 장애 예방 또는 치료용 약학 조성물.The pharmaceutical composition for preventing or treating learning disorders or memory disorders of claim 4, wherein the aqueous alcohol solution is an aqueous alcohol solution having a mixing ratio of lower alcohols of 10 to 95 (v / v)%.
  6. 건조 미나리 중량의 20 내지 200배의 탄소수 1 내지 4의 저급 알코올 수용액을 혼합하여 50 내지 90 ℃에서 4 내지 20 시간 추출하는 것을 특징으로 하는 학습장애 또는 기억력 장애 예방 또는 치료용 미나리 추출물의 제조방법.Method for producing a buttercup extract for preventing or treating learning disorders or memory disorders, characterized in that the mixture of 20 to 200 times the weight of dry buttercup low carbon aqueous solution of 1 to 4 carbon atoms to extract for 4 to 20 hours at 50 to 90 ℃.
  7. 제 6 항에 있어서, 상기 저급 알코올 수용액은 50 내지 80(v/v)%의 에탄올 수용액이고, 상기 에탄올 수용액으로 추출한 후, 그 추출물을 에틸아세테이트 또는 부탄올로 추출하는 것을 특징으로 하는 학습장애 또는 기억력 장애 예방 또는 치료용 미나리 추출물의 제조방법.According to claim 6, wherein the lower alcohol aqueous solution is 50 to 80 (v / v)% of ethanol aqueous solution, after the extraction with the ethanol aqueous solution, the extract is extracted with ethyl acetate or butanol, characterized in that learning disabilities or memory Method for preparing buttercup extract for preventing or treating disorders.
  8. 미나리 추출물을 유효성분으로 하는 학습능력 또는 기억력 증진용 건강기능식품.Health functional food for improving learning ability or memory with parsley extract as an active ingredient.
  9. 제 8 항에 있어서, 상기 미나리는 밭 미나리인 것을 특징으로 하는 학습능력 또는 기억력 증진용 건강기능식품.10. The health functional food for improving learning ability or memory of claim 8, wherein the buttercups are field buttercups.
  10. 제 8 항 또는 제 9 항에 있어서, 상기 건강기능식품의 형태는 분말, 과립, 정제, 캡슐 또는 음료 형태인 것을 특징으로 하는 학습능력 또는 기억력 증진용 건강기능식품.The health functional food according to claim 8 or 9, wherein the health functional food is in the form of powder, granules, tablets, capsules or beverages.
PCT/KR2011/006591 2010-09-08 2011-09-07 Composition containing oenanthe javanica extract as an active ingredient for preventing or treating learning disabilities or memory disorders, and method for preparing same WO2012033329A2 (en)

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