KR20210096905A - Composition for preventing or treating of Cognitive impairment and increasing cognitive function comprising Aristotelia chilensis - Google Patents
Composition for preventing or treating of Cognitive impairment and increasing cognitive function comprising Aristotelia chilensis Download PDFInfo
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Abstract
Description
본 발명은 마퀴베리 추출물을 유효성분으로 하는 인지기능 장애 예방, 치료 및 인지 기능 향상용 조성물에 관한 것이다.The present invention relates to a composition for preventing, treating, and improving cognitive function, comprising a maquiberry extract as an active ingredient.
일반적으로, 인지 기능 장애()는 뇌질환, 뇌상해, 중독, 노령화 등으로 인한 정신적, 행동적 장애 및 내분비 이상(Endocrine disorder), 대사 영양적 이상(Metabolic or Nutritional abnormalities),약물 등으로 인한 정신 질환을 포괄하는 것으로서, 증상의 정도에 따라 일시적 단기 기억 장애에 해당하는 건망증(Anmesia) 뿐만 아니라 전반적인 지남력과 판단력 장애를 유발하는 인지 기능 장애(증) 및 치매(Dementia)에서도 나타나는 뇌질환의 일종이다.In general, cognitive dysfunction () is mental and behavioral disorders due to brain disease, brain injury, addiction, aging, etc., endocrine disorders, metabolic or nutritional abnormalities, mental disorders caused by drugs, etc. It is a type of brain disease that encompasses diseases, and appears not only in Anmesia, which is a temporary short-term memory impairment, but also in cognitive dysfunction and dementia, which cause general disorientation and judgment, depending on the severity of the symptoms. .
심각한 수준의 알츠하이머 질환(Alzhimer's disease)으로 진행되기 전단계인 가벼운 인지 기능 장애(Mildcognitive impairment, MCI)는 최근 기억의 상실과 함께 학습능력, 집중력, 사고력의 저하 및 언어능력 저하 등의 증상을 포함하는데, MCI 환자의 80 % 이상이 10년 이내에 알츠하이머 질환으로 발전하며 이는 65세 이상의 건강한 인구의 1 % 만이 알츠하이머 질환에 걸리는 것에 비해 훨씬 높은 수치이다.Mild cognitive impairment (MCI), which is the pre-stage of severe Alzheimer's disease, includes symptoms such as a decrease in learning ability, concentration, thinking ability, and language ability along with a recent memory loss. More than 80% of patients with MCI will develop Alzheimer's disease within 10 years, compared to only 1% of the healthy population aged 65 years and older.
즉, 인지 기능 장애는 노화에 따른 퇴행성 기억 저하(Age-associated memory impairment, AAMI)와는 구별되며 발병 기전 및 경과 특성상 알츠하이머 치매와 밀접한 연관 관계를 갖는 질환으로서, 동일한 나이와 유사한 교육수준의 집단에 비해 현저한 기억력 및 인지기능 저하를 나타낸다.In other words, cognitive impairment is distinct from age-associated memory impairment (AAMI) and is a disease closely related to Alzheimer's dementia due to the pathogenesis and course characteristics. Significant memory and cognitive decline.
알츠하이머 치매 환자는 전체 치매 환자의 70 % 이상을 차지하며, 발병 원인은 완전히 규명되지 않았으나 최근까지 진행된 연구 결과에 따르면 신경섬유성 엉킴(Neurofibrillary tangles) 및 신경염성 플라크(Plaques)의 축적으로 나타나는 콜린성 신경의 쇠퇴가 주요 원인으로 추정된다.Alzheimer's dementia patients account for more than 70% of all dementia patients, and the cause of the disease is not fully understood. decline is believed to be the main cause.
다양한 인자, 예를 들어 흥분독성(Excitotoxicity), 산화적 스트레스, 성장인자 쇠퇴(Growth factor withdrawal), 사이토카인 또는 독성물질(Toxin) 등이 뇌신경계 질환으로 발전하는 신경 세포 손상을 야기할 수 있다.Various factors, for example, excitotoxicity, oxidative stress, growth factor withdrawal, cytokines or toxic substances (Toxin), etc. can cause nerve cell damage that develops into a cranial nervous system disease.
대부분의 신경 세포 손상은 이온자극성(Ionotropic) 또는 대사자극성(Metabotropic) 글루타메이트(Glutamate) 수용체의 과 자극에서 기인하는 것으로 추정된다.Most nerve cell damage is presumed to result from overstimulation of ionotropic or metabotropic glutamate receptors.
글루타메이트는 뇌에서 밀리몰 수준으로 발견되며, 뇌에서 N-메틸-D-아스파르테이트(Nmethyl-D-aspartate, NMDA) 수용체 및 비-NMDA 수용체에 작용하여 중추 흥분성 신경전달(Central excitatory neurotransmission)에 있어서 중요한 역할을 한다.Glutamate is found in millimolar levels in the brain, and acts on N-methyl-D-aspartate (NMDA) receptors and non-NMDA receptors in the brain, resulting in central excitatory neurotransmission. plays an important role.
글루타메이트와 같은 흥분성 아미노산은 신경 존속(Neuronal survival), 시냅토제네시스(Synaptogenesis), 신경 유연성(Neuronal plasticity), 학습(Learning), 기억 과정에 관여한다.Excitatory amino acids such as glutamate are involved in neuronal survival, synaptogenesis, neuronal plasticity, learning, and memory processes.
그러나 글루타메이트는 또한 급성 및 만성이라는 두 가지의 명확히 구분되는 기전에 의해 중추 신경계에서 신경성 세포 손실을 야기하는 것으로 알려져 있다.However, glutamate is also known to cause neuronal cell loss in the central nervous system by two clearly distinct mechanisms: acute and chronic.
예를 들어, 글루타메이트 신경전달 물질계에 있어서의 이상(Abnormalities)은 발작, 알츠하이머 질환, 파킨슨 질환, 허혈 및 척수 외상(Ischemia and spinal cord trauma) 등의 신경계 질환에 관여될 수 있다.For example, abnormalities in the glutamate neurotransmitter system may be involved in neurological disorders such as seizures, Alzheimer's disease, Parkinson's disease, ischemia and spinal cord trauma.
최근 노인성 치매 및 파킨슨 질환이 퇴행성 중추신경계 질환으로 인정되고 그 환자의 수가 날로 증가함에 따라 커다란 사회적 문제로 대두되면서 이의 예방이나 개선, 치료에 대한 중요성이 새롭게 부각되고 있다.Recently, as senile dementia and Parkinson's disease are recognized as degenerative central nervous system diseases and the number of the patients is increasing day by day, it has emerged as a great social problem, and the importance of prevention, improvement, and treatment thereof is newly emphasized.
알츠하이머 질환 환자는 콜린성, 아드레날린성, GABA성 및 글루타메이트성 신경 등 거의 모든 신경에 이상이 초래되나, 특히 콜린성 신경의 손실이 가장 심각한 것으로 알려져 있으며, 이에 따라 콜린성 신경의 이상을 회복시키거나 개선시키는 방향으로 치료제 개발이 활발히 이루어지고 있다.Alzheimer's disease patients cause almost all nerves, such as cholinergic, adrenergic, GABAergic and glutamatergic nerves, but in particular, it is known that the loss of cholinergic nerves is the most serious. Therefore, the development of therapeutics is actively being carried out.
예를 들어, 실험 대상 동물에 스코폴라민(Scopolamine)을 투여하여 콜린성 신경계에 이상을 유발시켜 알츠하이머 질환과 유사한 상태를 인위적으로 조작할 수 있는 방법이 알려지면서 인지 능력 개선 및 알츠하이머 질환의 치료제 개발이 진일보하게 되었다(Flood, J and Cherkin, A Scopolamine effects on memory retention in mice, Behav Neural Biol 45:169-184(1986))For example, as a method for artificially manipulating a condition similar to Alzheimer's disease by administering scopolamine to an experimental animal to induce abnormalities in the cholinergic nervous system, the improvement of cognitive ability and the development of a therapeutic agent for Alzheimer's disease (Flood, J and Cherkin, A Scopolamine effects on memory retention in mice, Behav Neural Biol 45:169-184 (1986))
스코폴라민을 투여하면 콜린성 신경 기능의 퇴행과 기억력 상실증이 나타나는 것은 물론, 습득력, 즉각적인 대응법, 활동기억(working memory)에 결함이 나타난다(Smith, 1988; Giacobini, E and Cuadra, G(1994))Administration of scopolamine leads to degeneration of cholinergic nerve function and amnesia, as well as defects in acquisition, immediate response, and working memory (Smith, 1988; Giacobini, E and Cuadra, G (1994)).
이러한 증상은 콜린성 신경의 효능제인 아레콜린(Arecoline) 및 옥소트레모린(Oxotremorine)이나 아세틸콜린의 분해를 억제시킴으로써 세포 내의 아세틸콜린의 농도를 유지시키는 아세틸콜린에스테라제 저해제인 타크린(Tacrine) 등의 투여에 의하여 완화되었다.These symptoms include Arecoline and Oxotremorine, which are agonists of cholinergic nerves, or Tacrine, an acetylcholinesterase inhibitor that maintains the concentration of acetylcholine in cells by inhibiting the breakdown of acetylcholine. was relieved by the administration of
다만, 타크린이 임상에서 일부 사용되고 있기는 하나 간독성, 짧은 반감기 및 낮은 생체 내 이용률 등의 문제가 제기되고 있어 새로운 대체 약물을 찾기 위한 연구가 활발히 진행되고 있다.However, although tacrine is partially used in clinical practice, problems such as hepatotoxicity, short half-life, and low bioavailability have been raised, and studies to find new alternative drugs are being actively conducted.
아세틸콜린(acetylcholine)은 기억과 학습능력을 조절하는 신경전달 물질의 하나이며, 뇌의 아세틸콜린의 양이 정상인보다 적게 되면 인지 능력이 저하된다. 아세틸콜린 에스테라제(Acetylcholinesterase; AchE)는 아세틸콜린의 분해효소로서 아세틸콜린의 부족의 중요한 원인 중 하나이다. 따라서, AchE의 활성을 저해함으로 인해 인지능 개선의 효과를 기대할 수 있다. Acetylcholine is one of the neurotransmitters that regulate memory and learning ability, and when the amount of acetylcholine in the brain is lower than that of normal people, cognitive ability is reduced. Acetylcholinesterase (AchE) is an acetylcholine degrading enzyme and is one of the major causes of acetylcholine deficiency. Therefore, the effect of improving cognitive ability can be expected by inhibiting the activity of AchE.
마퀴베리(Aristotelia chilensis)는 퍼플 푸드(purple food)로서 아사이베리의 약 7배, 아로니아의 약 66배의 항산화 지수를 가져 슈퍼 항산화제로 보고된 바 있으며, 항산화 성분인 안토시아닌(anthocyanin)과 폴리페놀(polyphenol)이 풍부한 열매로 현재 마퀴베리의 효능에 대한 연구가 활발히 이루어지고 있다. Marqui berry (Aristotelia chilensis) is a purple food and has an antioxidant index that is about 7 times that of acai berry and about 66 times that of aronia, and has been reported as a super antioxidant. As a fruit rich in polyphenol, research on the efficacy of maqui berry is being actively conducted.
안토시아닌은 로돕신(rhodopsin)이라는 망막색소의 합성을 촉진시켜 백내장이나 녹내장 등 안과 질환 등을 예방하는데 유용한 항산화 물질이다. 피부 노화 물질 중 하나인 활성산소종을 감소시키며, 지질층과 콜라겐의 산화를 방지하는 피부 생리 활성에 대한 연구가 보고된 바 있다.Anthocyanins are useful antioxidants for preventing eye diseases such as cataracts and glaucoma by promoting the synthesis of a retinal pigment called rhodopsin. It has been reported that research on skin physiological activity that reduces reactive oxygen species, one of skin aging substances, and prevents oxidation of lipid layer and collagen.
인지 기능 장애 치료를 위한 기술 중 하나로서, 한국등록특허 제10-0861730호 '연자육 추출물을 함유하는 인지기능 장애 관련 질환의 예방 및 치료용 조성물'은, 연자육 추출물을 유효성분으로 하여 인지 기능 장애를 완화하는 방법을 개시하고 있다. As one of the technologies for the treatment of cognitive dysfunction, Korea Patent No. 10-0861730, 'Composition for the prevention and treatment of cognitive dysfunction-related diseases containing yeonjayuk extract', uses yeonjayuk extract as an active ingredient to treat cognitive dysfunction. A method of mitigation is disclosed.
그러나 상술한 바와 같이 한국등록특허 제10-0861730호는 본 발명의 마퀴베리 추출물을 유효성분으로 하는 인지기능 장애의 예방 또는 치료에 적용하는 내용은 기재되어 있지 않다.However, as described above, Korean Patent No. 10-0861730 does not describe the application of the maquiberry extract of the present invention to the prevention or treatment of cognitive dysfunction as an active ingredient.
본 발명은 상기의 필요성에 의하여 안출된 것으로서 본 발명의 목적은 신규한 인지 기능 개선용 조성물을 제공하는 것이다.The present invention has been devised in response to the above needs, and an object of the present invention is to provide a novel composition for improving cognitive function.
상기의 목적을 달성하기 위하여 본 발명은 마퀴베리 추출물을 유효성분으로 포함하는 인지 기능 항상용 식품 조성물을 제공한다.In order to achieve the above object, the present invention provides a food composition for constant cognitive function comprising a maquiberry extract as an active ingredient.
본 발명의 일 구현예에 있어서, In one embodiment of the present invention,
상기 마퀴베리 추출물은 (a) 물, (b) 탄소수 1-4의 무수 또는 함수 저급 알코올, (c) 상기 저급 알코올과 물과의 혼합용매, (d) 아세톤, (e) 에틸 아세테이트, (f) 클로로포름, (g) 부틸아세테이트, (h) 1,3-부틸렌글리콜, (i) 헥산 및 (j) 디에틸에테르로 구성된 군으로부터 추출 용매로부터 추출된 것이 바람직하나 이에 한정되지 아니한다.The maquiberry extract is (a) water, (b) anhydrous or hydrated lower alcohol having 1-4 carbon atoms, (c) a mixed solvent of the lower alcohol and water, (d) acetone, (e) ethyl acetate, (f ) chloroform, (g) butyl acetate, (h) 1,3-butylene glycol, (i) hexane and (j) diethyl ether extracted from the extraction solvent from the group consisting of, but is not limited thereto.
본 발명의 다른 구현예에 있어서, In another embodiment of the present invention,
상기 마퀴베리 추출물은 에탄올로부터 추출된 것이 더욱 바람직하나 이에 한정되지 아니한다.The maquiberry extract is more preferably extracted from ethanol, but is not limited thereto.
또 본 발명은 마퀴베리 추출물을 유효성분으로 포함하는 인지 기능 장애 예방 또는 치료용 약학 조성물을 제공한다.In addition, the present invention provides a pharmaceutical composition for preventing or treating cognitive dysfunction comprising a maquiberry extract as an active ingredient.
본 발명의 일 구현예에 있어서, In one embodiment of the present invention,
상기 마퀴베리 추출물은 (a) 물, (b) 탄소수 1-4의 무수 또는 함수 저급 알코올, (c) 상기 저급 알코올과 물과의 혼합용매, (d) 아세톤, (e) 에틸 아세테이트, (f) 클로로포름, (g) 부틸아세테이트, (h) 1,3-부틸렌글리콜, (i) 헥산 및 (j) 디에틸에테르로 구성된 군으로부터 추출 용매로부터 추출된 것이 바람직하나 이에 한정되지 아니한다.The maquiberry extract is (a) water, (b) anhydrous or hydrated lower alcohol having 1-4 carbon atoms, (c) a mixed solvent of the lower alcohol and water, (d) acetone, (e) ethyl acetate, (f ) chloroform, (g) butyl acetate, (h) 1,3-butylene glycol, (i) hexane and (j) diethyl ether extracted from the extraction solvent from the group consisting of, but is not limited thereto.
본 발명의 다른 구현예에 있어서, In another embodiment of the present invention,
상기 마퀴베리 추출물은 에탄올로부터 추출된 것이 더욱 바람직하나 이에 한정되지 아니한다.The maquiberry extract is more preferably extracted from ethanol, but is not limited thereto.
또한 본 발명은 마퀴베리 추출물을 유효성분으로 포함하는 아세틸콜린 에스테라제 활성 저해용 조성물을 제공한다.In addition, the present invention provides a composition for inhibiting acetylcholine esterase activity comprising a maquiberry extract as an active ingredient.
본 발명의 일 구현예에 있어서, In one embodiment of the present invention,
상기 마퀴베리 추출물은 (a) 물, (b) 탄소수 1-4의 무수 또는 함수 저급 알코올, (c) 상기 저급 알코올과 물과의 혼합용매, (d) 아세톤, (e) 에틸 아세테이트, (f) 클로로포름, (g) 부틸아세테이트, (h) 1,3-부틸렌글리콜, (i) 헥산 및 (j) 디에틸에테르로 구성된 군으로부터 추출 용매로부터 추출된 것이 바람직하나 이에 한정되지 아니한다.The maquiberry extract is (a) water, (b) anhydrous or hydrated lower alcohol having 1-4 carbon atoms, (c) a mixed solvent of the lower alcohol and water, (d) acetone, (e) ethyl acetate, (f ) chloroform, (g) butyl acetate, (h) 1,3-butylene glycol, (i) hexane and (j) diethyl ether extracted from the extraction solvent from the group consisting of, but is not limited thereto.
본 발명의 다른 구현예에 있어서, In another embodiment of the present invention,
상기 마퀴베리 추출물은 에탄올로부터 추출된 것이 더욱 바람직하나 이에 한정되지 아니한다.The maquiberry extract is more preferably extracted from ethanol, but is not limited thereto.
또한 본 발명은 인 비트로에서 세포에 마퀴베리 추출물을 처리하여 상기 세포에서 아세틸콜린 에스테라제 활성을 저해하는 방법을 제공한다.In addition, the present invention provides a method for inhibiting acetylcholine esterase activity in the cell by treating the maquiberry extract in vitro.
본 발명의 일 구현예에 있어서, 상기 추출물은 세포에 0.03 내지 1mg/ml 처리하는 것이 바람직하나 이에 한정되지 아니한다.In one embodiment of the present invention, the extract is preferably treated with 0.03 to 1 mg/ml cells, but is not limited thereto.
본 발명의 조성물에서 이용되는 마퀴베리 추출물을 마퀴베리에 추출용매를 처리하여 얻는 경우에는, 다양한 추출용매가 이용될 수 있다. 바람직하게는, 극성 용매 또는 비극성 용매를 이용할 수 있다. When the maqui berry extract used in the composition of the present invention is obtained by treating maqui berry with an extraction solvent, various extraction solvents may be used. Preferably, a polar solvent or a non-polar solvent may be used.
극성 용매로서 적합한 것은, (i) 물, (ii) 알코올(바람직하게는, 메탄올, 에탄올, 프로판올, 부탄올, 노말-프로판올, 이소-프로판올, 노말-부탄올, 1-펜탄올, 2-부톡시에탄올 또는 에틸렌글리콜), (iii) 아세트산, (iv) DMFO(dimethylformamide) 및 (v) DMSO(dimethyl sulfoxide)를 포함한다. 비극성 용매로서 적합한 것은, 아세톤, 아세토나이트릴, 에틸 아세테이트, 메틸 아세테이트, 플루오로알칸, 펜탄, 헥산, 2,2,4-트리메틸펜탄, 데칸, 사이클로헥산, 사이클로펜탄, 디이소부틸렌, 1-펜텐, 1-클로로부탄, 1-클로로펜탄, o-자일렌, 디이소프로필 에테르, 2-클로로프로판, 톨루엔, 1-클로로프로판, 클로로벤젠, 벤젠, 디에틸 에테르, 디에틸 설파이드, 클로로포름, 디클로로메탄, 1,2-디클로로에탄, 어닐린, 디에틸아민, 에테르, 사염화탄소, 메틸렌클로라이드 및 THF를 포함한다.Suitable as polar solvents are: (i) water, (ii) alcohols (preferably methanol, ethanol, propanol, butanol, n-propanol, iso-propanol, n-butanol, 1-pentanol, 2-butoxyethanol or ethylene glycol), (iii) acetic acid, (iv) DMFO (dimethylformamide) and (v) DMSO (dimethyl sulfoxide). Suitable nonpolar solvents are acetone, acetonitrile, ethyl acetate, methyl acetate, fluoroalkane, pentane, hexane, 2,2,4-trimethylpentane, decane, cyclohexane, cyclopentane, diisobutylene, 1- Pentene, 1-chlorobutane, 1-chloropentane, o-xylene, diisopropyl ether, 2-chloropropane, toluene, 1-chloropropane, chlorobenzene, benzene, diethyl ether, diethyl sulfide, chloroform, dichloro methane, 1,2-dichloroethane, aniline, diethylamine, ether, carbon tetrachloride, methylenechloride and THF.
보다 바람직하게는, 본 발명에서 이용되는 추출용매는 (a) 물, (b) 탄소수 1-4의 무수 또는 함수 저급 알코올(메탄올, 에탄올, 프로판올, 부탄올 등), (c) 상기 저급 알코올과 물과의 혼합용매, (d) 아세톤, (e) 에틸 아세테이트, (f) 클로로포름, (g) 부틸아세테이트, (h) 1,3-부틸렌글리콜, (i) 헥산 및 (j) 디에틸에테르를 포함한다. More preferably, the extraction solvent used in the present invention is (a) water, (b) anhydrous or hydrated lower alcohol having 1-4 carbon atoms (methanol, ethanol, propanol, butanol, etc.), (c) the lower alcohol and water mixed solvent with, (d) acetone, (e) ethyl acetate, (f) chloroform, (g) butyl acetate, (h) 1,3-butylene glycol, (i) hexane and (j) diethyl ether include
가장 바람직하게는, 본 발명의 추출물은 물, 메탄올, 에탄올 또는 이의 조합을 마퀴베리에 처리하여 수득한 것이다.Most preferably, the extract of the present invention is obtained by treating maquiberries with water, methanol, ethanol or a combination thereof.
본 발명의 바람직한 구현예에 따르면, 상기 마퀴베리 추출물은 마퀴베리 중량의 5 내지 15 배, 보다 바람직하게는 10 배의 물을 첨가하고 25 내지 100℃, 보다 바람직하게는 70 내지 95℃의 온도에서 1 내지 72 시간, 보다 더 바람직하게는 4 내지 24 시간 동안 추출한 후 여과 또는 원심 분리하는 방법에 의해 제조되거나,According to a preferred embodiment of the present invention, the maquiberry extract is added with water 5 to 15 times, more preferably 10 times the weight of the maquiberry, and at a temperature of 25 to 100° C., more preferably 70 to 95° C. Prepared by a method of filtration or centrifugation after extraction for 1 to 72 hours, more preferably 4 to 24 hours, or
마퀴베리 중량의 1 내지 10배, 바람직하게는 5배의 유기용매, 바람직하게는 에탄올을 첨가하고 실온 내지 60℃의 온도에서 1 내지 72 시간, 바람직하게 는 4 내지 24 시간 동안 교반하면서 추출한 후 여과 또는 원심 분리하여 얻어진 추출액을 감압 농축하는 방법에 의하여 제조될 수 있다.1 to 10 times, preferably 5 times the weight of maquiberry, an organic solvent, preferably ethanol, is added, and extracted while stirring at a temperature of room temperature to 60° C. for 1 to 72 hours, preferably 4 to 24 hours, followed by filtration. Alternatively, it may be prepared by a method of concentrating the extract obtained by centrifugation under reduced pressure.
상기 추출방법들에서 추출공정은 필요에 따라 2회 이상 반복하여 실시할 수 있으며, 여과 또는 원심 분리 후 얻어진 여액을 감압 건조, 분무 건조 또는 동결 건조하는 등과 같은 추가적인 과정에 의해 분말 상태로 제조될 수 있다.In the above extraction methods, the extraction process may be repeated two or more times as needed, and the filtrate obtained after filtration or centrifugation may be prepared in a powder state by an additional process such as drying under reduced pressure, spray drying or freeze drying. there is.
본 명세서에서 사용되는 용어 ‘추출물’은 상술한 바와 같이 당업계에서 조추출물(crude extract)로 통용되는 의미를 갖지만, 광의적으로는 추출물을 추가적으로 분획(fractionation)한 분획물도 포함한다. 즉, 마퀴베리 추출물은 상술한 추출용매를 이용하여 얻은 것뿐만 아니라, 여기에 정제과정을 추가적으로 적용하여 얻은 것도 포함한다. 예컨대, 상기 추출물을 일정한 분자량 컷-오프 값을 갖는 한외 여과막을 통과시켜 얻은 분획, 다양한 크로마토그래피(크기, 전하, 소수성 또는 친화성에 따른 분리를 위해 제작된 것)에 의한 분리 등, 추가적으로 실시된 다양한 정제 방법을 통해 얻어진 분획도 본 발명의 마퀴베리 추출물에 포함되는 것이다.As used herein, the term 'extract' has the meaning commonly used as a crude extract in the art as described above, but in a broad sense also includes a fraction obtained by additionally fractionating the extract. That is, the maquiberry extract includes not only those obtained by using the above-described extraction solvent, but also those obtained by additionally applying a purification process thereto. For example, a fraction obtained by passing the extract through an ultrafiltration membrane having a constant molecular weight cut-off value, separation by various chromatography (prepared for separation according to size, charge, hydrophobicity or affinity), etc. The fraction obtained through the purification method is also included in the maquiberry extract of the present invention.
본 발명의 신경퇴행성 질환의 예방, 개선 또는 치료용 조성물 또는 인지기능 개선용 조성물은 아세틸콜린에스터라제(acetylcholine esterase)의 활성을 억제하는 작용을 나타낸다. The composition for preventing, improving or treating neurodegenerative diseases or the composition for improving cognitive function of the present invention exhibits an action of inhibiting the activity of acetylcholine esterase.
아세틸콜린에스터라제는 체내 신경 전달물질 중의 하나인 아세틸콜린을 콜린과 아세트산으로 가수분해하는 효소로서, 체내 아세틸콜린의 농도 증감과 깊은 관련을 가지고 있다. 이러한 아세틸콜린에스터라제의 작용을 억제하여 아세틸콜린의 양을 증가시키는 물질은 체내 아세틸콜린의 부족으로 인하여 유발되는 질환을 예방 및 치료하기 위한 용도로 사용할 수 있다.Acetylcholinesterase is an enzyme that hydrolyzes acetylcholine, one of the neurotransmitters in the body, into choline and acetic acid. Substances that increase the amount of acetylcholine by inhibiting the action of acetylcholinesterase can be used for preventing and treating diseases caused by lack of acetylcholine in the body.
상기한 질환으로는 알쯔하이머 질환, 헌팅톤 질병, 파킨슨씨 질병, 근위축성 측삭 경화증, 치매(Terry AV et al, J Pharmacol Exp Ther, 306:821-827 (2003); Giacobini E Cholinesterases Neurochem Res, 28:515-522(2003); Auld DS et al, Prog Neurobiol, 68:209-245 (2002)), 기억력저하(Myhrer T Brain Res Rev,41:268-287 (2003); Graves L et al, Trends Neurosci, 24:237-243 (2001)), 중증근무력증(Levinson AI et al, Immunol Res, 27:399-408 (2003); Spiess JL et al, J Pain Symptom Manage, 26:684-686 (2003); Fotiou F et al, J Neuropsychiatry Clin Neurosci, 12:514-515 (2000)) 및 녹내장 (Millard CB et al, 64:1909-1918(1995); Hyndiuk RA et al, Lens Eye Toxic Res, 9:331-350(1992)) 등이 있다.The aforementioned diseases include Alzheimer's disease, Huntington's disease, Parkinson's disease, amyotrophic lateral sclerosis, dementia (Terry AV et al, J Pharmacol Exp Ther, 306:821-827 (2003); Giacobini E Cholinesterases Neurochem Res, 28: 515-522 (2003); Auld DS et al, Prog Neurobiol, 68:209-245 (2002)), memory loss (Myhrer T Brain Res Rev, 41:268-287 (2003); Graves L et al, Trends Neurosci , 24:237-243 (2001)), myasthenia gravis (Levinson AI et al, Immunol Res, 27:399-408 (2003); Spiess JL et al, J Pain Symptom Manage, 26:684-686 (2003); Fotiou F et al, J Neuropsychiatry Clin Neurosci, 12:514-515 (2000)) and glaucoma (Millard CB et al, 64:1909-1918 (1995); Hyndiuk RA et al, Lens Eye Toxic Res, 9:331- 350 (1992)) and others.
본 발명의 조성물은 식품 조성물로 제조될 수 있다.The composition of the present invention can be prepared as a food composition.
본 발명의 마퀴베리 추출물을 포함하는 조성물을 여러 식품에 첨가하여 인지기능 개선용 식품으로 안전하고 유용하게 사용할 수 있으며 특히, 기억력 증진의 목적으로 식품 또는 음료에 첨가될 수 있다. The composition containing the maquiberry extract of the present invention can be safely and usefully used as a food for improving cognitive function by adding it to various foods, and in particular, it can be added to food or beverages for the purpose of enhancing memory.
아울러, 본 발명에 따른 조성물은 마퀴베리로부터 추출된 것이므로 인체에 무해하며, 제조방법이 간단하여 대량으로 상품화가능하다.In addition, since the composition according to the present invention is extracted from maqui berry, it is harmless to the human body, and can be commercialized in large quantities due to a simple manufacturing method.
본 발명의 신경퇴행성 질환의 예방 및 개선용 또는 인지기능 개선용 식품의 개발을 위하여 본 발명의 마퀴베리 추출물을 첨가할 수 있는 식품의 형태는, 예를 들어 떡, 한과, 빵, 과자 및 면 등의 식품류; 차, 쥬스, 탄산음료 및 이온음료 등의 음료류; 우유, 요구르트 등의 가공유류; 껌류; 산제, 정제 및 캡슐제 등의 건강식품 제제류 등이 될 수 있다. For the prevention and improvement of the neurodegenerative disease of the present invention or for the development of food for improving cognitive function, the form of food to which the maquiberry extract of the present invention can be added is, for example, rice cakes, Korean sweets, bread, sweets, noodles, etc. of food products; beverages such as tea, juice, carbonated beverages and ionized beverages; Processed milk, such as milk and yogurt; gum; It may be health food preparations such as powders, tablets and capsules.
본 발명의 식품 조성물은, 필수성분으로서 상기 마퀴베리 추출물을 지시된 비율로 함유하는 것 외에 여러 가지 향미제 또는 천연 탄수화물 등을 추가 성분으로서 함유할 수 있다. 향미제는 천연향미제로 레바우디오시드 A 및 글리시르히진 등의 스테비아 추출물, 또는 타우마틴 등이 함유될 수 있고, 합성향미제로 아스파르탐 등이 함유될 수 있다. The food composition of the present invention may contain various flavoring agents or natural carbohydrates as an additional component in addition to containing the maquiberry extract in the indicated ratio as an essential component. The flavoring agent is a natural flavoring agent and may include a stevia extract such as rebaudioside A and glycyrrhizin, or thaumatin, and aspartame as a synthetic flavoring agent.
천연 탄수화물은 포도당 및 과당 등의 단당류; 말토스 및 수크로스 등의 이당류; 덱스트린 및 시클로덱스트린 등의 다당류; 또는 자일리톨, 소르비톨 및 에리트리톨 등의 당알콜 등이 있다. Natural carbohydrates include monosaccharides such as glucose and fructose; disaccharides such as maltose and sucrose; polysaccharides such as dextrin and cyclodextrin; or sugar alcohols such as xylitol, sorbitol and erythritol.
이외에도 필요에 따라 항세균제, 킬레이트제, 완충제, 보존제와 같은 보조제를 포함시킬 수도 있다.In addition, if necessary, adjuvants such as antibacterial agents, chelating agents, buffers, and preservatives may be included.
본 발명의 조성물은 약제학적 조성물로도 제조될 수 있다.The composition of the present invention may also be prepared as a pharmaceutical composition.
본 발명의 바람직한 구현예에 따르면, 본 발명의 조성물은 (a) 상술한 본 발명의 마퀴베리 추출물의 약제학적 유효량; 및 (b) 약제학적으로 허용되는 담체를 포함하는 약제학적 조성물이다. According to a preferred embodiment of the present invention, the composition of the present invention comprises (a) a pharmaceutically effective amount of the above-described maquiberry extract of the present invention; and (b) a pharmaceutically acceptable carrier.
본 명세서에서 용어 “약제학적 유효량”은 상술한 마퀴베리 추출물의 효능 또는 활성을 달성하는 데 충분한 양을 의미한다.As used herein, the term “pharmaceutically effective amount” refers to an amount sufficient to achieve the efficacy or activity of the above-mentioned maquiberry extract.
본 발명의 조성물이 약제학적 조성물로 제조되는 경우, 본 발명의 약제학적 조성물은 약제학적으로 허용되는 담체를 포함한다. When the composition of the present invention is prepared as a pharmaceutical composition, the pharmaceutical composition of the present invention includes a pharmaceutically acceptable carrier.
본 발명의 약제학적 조성물에 포함되는 약제학적으로 허용되는 담체는 제제시에 통상적으로 이용되는 것으로서, 락토스, 덱스트로스, 수크로스, 솔비톨, 만니톨, 전분, 아카시아 고무, 인산 칼슘, 알기네이트, 젤라틴, 규산 칼슘, 미세결정성 셀룰로스, 폴리비닐피롤리돈, 셀룰로스, 물, 시럽, 메틸 셀룰로스, 메틸히드록시벤조에이트, 프로필히드록시벤조에이트, 활석, 스테아르산 마그네슘 및 미네랄 오일 등을 포함하나, 이에 한정되는 것은 아니다. Pharmaceutically acceptable carriers included in the pharmaceutical composition of the present invention are commonly used in formulation, and include lactose, dextrose, sucrose, sorbitol, mannitol, starch, acacia gum, calcium phosphate, alginate, gelatin, calcium silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, water, syrup, methyl cellulose, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil, and the like. it's not going to be
본 발명의 약제학적 조성물은 상기 성분들 이외에 윤활제, 습윤제, 감미제,향미제, 유화제, 현탁제, 보존제 등을 추가로 포함할 수 있다. 적합한 약제학적으로 허용되는 담체 및 제제는 Remington's Pharmaceutical Sciences(19th ed, 1995)에 상세히 기재되어 있다.The pharmaceutical composition of the present invention may further include a lubricant, a wetting agent, a sweetening agent, a flavoring agent, an emulsifying agent, a suspending agent, a preservative, and the like, in addition to the above components. Suitable pharmaceutically acceptable carriers and agents are described in detail in Remington's Pharmaceutical Sciences (19th ed, 1995).
본 발명의 마퀴베리 추출물 함유 조성물을 인지기능 개선용 약제로 사용하는 경우 경구 또는 비경구 모두 가능하며, 비경구 투여는 정맥내 주입, 피하 주입, 근육 주입, 복강 주입, 경피 투여 등을 포함한다. When the composition containing maquiberry extract of the present invention is used as a medicament for improving cognitive function, both oral and parenteral administration are possible, and parenteral administration includes intravenous injection, subcutaneous injection, intramuscular injection, intraperitoneal injection, transdermal administration, and the like.
상기 조성물의 제형은 사용방법에 따라 달라질 수 있으나, 경고제 (Plasters), 과립제 (Granule), 산제 (Powders), 시럽제(Syrups), 액제 (solutions), 유동엑스제 (FluidextractsI), 유제 (Emulsions), 현탁제 (Suspensions), 침제(Infusions), 정제 (Tablets), 주사제 (Injections), 캅셀제 (Capsules) 및 환제(Pills)등으로 제조할 수 있다.The formulation of the composition may vary depending on the method of use, but warning agents (Plasters), granules (Granule), powders (Powders), syrups (Syrups), solutions (solutions), fluid extracts (FluidextractsI), emulsions (Emulsions) , suspensions, infusions, tablets, injections, capsules, and pills.
아울러, 본 발명의 약제학적 조성물의 투여량은 환자의 연령, 성별, 상태, 체내에서 활성 성분의 흡수도, 불활성율 및 병용되는 약물을 고려하여 결정하는 것이 좋으며, 1일 마퀴베리 추출물을 기준으로 하였을 때 0.001 ㎎/㎏(체중) 내지 500 ㎎/㎏(체중)으로 투여할 수 있다.In addition, the dosage of the pharmaceutical composition of the present invention is preferably determined in consideration of the patient's age, sex, condition, absorption of active ingredients in the body, inactivation rate, and drugs used in combination, and based on the daily maquiberry extract It can be administered at 0.001 mg/kg (body weight) to 500 mg/kg (body weight).
본 발명에 따른 마퀴베리 추출물 함유 인지기능 개선용 조성물은 제형 및 사용방법에 따라 약리학적으로 허용가능한 담체나 부형제를 더 포함할 수 있다. The composition for improving cognitive function containing maquiberry extract according to the present invention may further include a pharmaceutically acceptable carrier or excipient depending on the formulation and usage method.
이 경우 조성물 내 마퀴베리 추출물 함량은 0.001 내지 20 중량% 일 수 있는데, 이의 함량이 0.001 중량% 미만인 경우 효과적인 효능을 위해선 다량의 투여가 필요할 수 있으며, 20중량% 초과하는 경우 사용량에 비해 효능이 일정할 수 있어 비경제적일 수 있다. 그러나 마퀴베리 추출물의 함량은 사용 방법 및 사용목적에 따라 적절히 조절하는 것이 바람직하며, 바람직하게는 1 내지 10 중량%로 첨가할 수 있다.In this case, the content of the maquiberry extract in the composition may be 0.001 to 20% by weight, and if its content is less than 0.001% by weight, a large amount of administration may be required for effective efficacy, and if it exceeds 20% by weight, the efficacy is constant compared to the amount used It can be uneconomical. However, the content of the maquiberry extract is preferably adjusted appropriately according to the method of use and the purpose of use, and may preferably be added in an amount of 1 to 10% by weight.
본 발명을 통하여 알 수 있는 바와 같이, AchE inhibition assay를 통하여 마퀴베리 70% EtOH 추출물 sample에서 농도 의존적으로 실험관내 뿐만 아니라 신경세포 내의 AchE 활성 저해 효과가 나타나는 것을 확인했다. As can be seen from the present invention, it was confirmed that the concentration-dependent inhibitory effect of AchE activity in neurons as well as in vitro in the maquiberry 70% EtOH extract sample was shown through the AchE inhibition assay.
본 발명은 마퀴베리 추출물의 유효성분은 AchE 활성 저해를 통한 인지능 개선에 효과를 검증하였다.The present invention verified the effect of the active ingredient of the maquiberry extract on improving cognitive ability through inhibition of AchE activity.
도 1은 아세틸콜린 에스테라제(Acetylcholinesterase; AchE)의 신호전달 및 작용 및 저해 기작을 나타낸 그림,
도 2는 마퀴베리 70% EtOH 추출물 실험관 내 AchE 활성 저해 평가를 나타낸그림,
도 3은 마퀴베리 70% EtOH 추출물의 세포내 AchE 활성 저해 평가를 나타낸그림으로, (A) 세포 독성 평가, (B) AchE 활성 저해 평가Figure 1 is a figure showing the signaling and action and inhibition mechanism of acetylcholinesterase (Acetylcholinesterase; AchE),
Figure 2 is a figure showing the evaluation of inhibition of AchE activity in vitro with maquiberry 70% EtOH extract;
Figure 3 is a diagram showing the evaluation of inhibition of AchE activity in cells of maquiberry 70% EtOH extract, (A) cytotoxicity evaluation, (B) AchE activity inhibition evaluation
이하, 본 발명을 제조예, 및 실시예에 의하여 더욱 상세히 설명한다.Hereinafter, the present invention will be described in more detail by way of preparation examples and examples.
단, 하기의 제조예, 및 실시예는 본 발명을 구체적으로 설명하기 위해 제공되는 것일 뿐, 본 발명의 범위가 이들 제조예, 및 실시예에 의하여 한정되는 것으로 해석되지 아니한다.However, the following preparation examples and examples are only provided to explain the present invention in detail, and the scope of the present invention is not to be construed as being limited by these preparation examples and examples.
제조예 1: 마퀴베리 추출물의 제조Preparation Example 1: Preparation of maquiberry extract
마퀴베리는 칠레산 동결건조 분말을 구입하여 시료로 사용하였으며, 마퀴베리 powder 1g에 70% EtOH 10ml을 넣고 4℃에서 24hr 동안 교반하면서 추출한 후 Marqui berry was purchased freeze-dried powder from Chile and used as a sample, and 10ml of 70% EtOH was added to 1g of maquiberry powder and extracted while stirring at 4℃ for 24hr.
4000rpm, 10min, 4℃로 원심분리하여 상등액을 취하여 추출액을 얻었다.The supernatant was obtained by centrifugation at 4000rpm, 10min, 4℃ to obtain an extract.
실시예 1: 마퀴베리 추출물의 Acetylcholinesterase 활성 억제 효능Example 1: Acetylcholinesterase activity inhibitory effect of maquiberry extract
뇌세포 안에서의 신경전달 물질인 Acetylcholine을 분해하는 효소인 Acetylcholinesterase (AChE)의 활성을 저해하게 되면 뇌세포 내의 신경전달 물질(콜린)의 농도가 높아져 원활한 신경전달에 도움이 되어 인지능 개선에 도움이 된다. AchE inhibition assay를 통하여 마퀴베리 추출물이 실험관(시판효소)내 뿐만 아니라 신경세포주(mHypo-42)에서의 AchE의 활성을 농도 의존적으로 저해함을 확인하였다.When the activity of Acetylcholinesterase (AChE), an enzyme that decomposes Acetylcholine, a neurotransmitter in brain cells, is inhibited, the concentration of a neurotransmitter (choline) in brain cells increases, which helps smooth nerve transmission and helps improve cognitive intelligence. do. Through the AchE inhibition assay, it was confirmed that the maquiberry extract inhibited the activity of AchE in a concentration-dependent manner not only in the test tube (commercial enzyme) but also in the neuronal cell line (mHypo-42).
실험관내 인지능 효율 확인 실험 (AchE inhibition assay)In vitro cognitive efficiency confirmation experiment (AchE inhibition assay)
96well plate에 실험물질들을 농도별로 각 well에 넣고 1unit 효소 (Acetylcholinesteras-Sigma-Aldrich), 0.1M Sodium phosphate buffer(PH 7.0)와 1mM 5,5'-Dithiobis-(2-Nitrobenzoic Acid)(DTNB)을 넣은 후, 10분 pre-incubation을 해 주고, 0.5mM 효소기질을 첨가해준 후, 37℃에서 10분 배양한다. 412nm에서 Spectrophotometer로 측정하였다. In a 96-well plate, put the test substances into each well by concentration, and add 1 unit enzyme (Acetylcholinesteras-Sigma-Aldrich), 0.1M sodium phosphate buffer (PH 7.0) and 1mM 5,5'-Dithiobis-(2-Nitrobenzoic Acid) (DTNB). After addition, pre-incubation is performed for 10 minutes, 0.5 mM enzyme substrate is added, and incubated at 37°C for 10 minutes. Measurements were made with a Spectrophotometer at 412 nm.
세포 안전성 시험 (MTT assay)Cell safety test (MTT assay)
세포배양cell culture
시상하부 세포주인 mHypo-42 세포를 24 well dish 배양접시에 접종하였다. 생육 배지로는 Penicillin(100UI/ml), Streptomycin(100ug/ml), 10% FBS(fetal bovine serum)을 함유하는 DMEM(Dulbecco's Modified Eagle's Medium)을 사용했다. 실험기간 동안 세포는 5% CO₂를 포함하는 37℃ incubator에서 배양하였다.The hypothalamic cell line, mHypo-42 cells, was inoculated into a 24-well dish culture dish. As a growth medium, DMEM (Dulbecco's Modified Eagle's Medium) containing Penicillin (100UI/ml), Streptomycin (100ug/ml), and 10% FBS (fetal bovine serum) was used. During the experiment, cells were cultured in an incubator at 37°C containing 5% CO₂.
실험 방법Experimental method
세포 내에서 시료의 효소 활성 저해를 탐색하기 위해서는 세포들에서 세포 독성을 나타내지 않는 농도를 설정하는 것이 우선이다. 이러한 농도를 설정하기 위해서 실제 실험에 사용하는 세포들을 배양하면서 여러 농도의 시료를 세포에 처리한 후 세포의 성장, 증식, 세포 독성에 미치는 영향을 조사하는 방법으로 MTT assay를 사용한다. In order to search for inhibition of enzymatic activity of a sample in cells, it is priority to set a concentration that does not show cytotoxicity in cells. In order to set these concentrations, the MTT assay is used as a method to examine the effects on cell growth, proliferation, and cytotoxicity after treatment with samples of various concentrations while culturing the cells used in the actual experiment.
본 실험에서 사용한 구체적인 실험 방법으로는 시상하부 세포주인 mHypo-42 세포를 24well plate에 8x10⁴로 분주한 후, 5% CO₂를 포함하는 37℃ incubator에서 24시간 배양하였다. As a specific experimental method used in this experiment, mHypo-42 cells, a hypothalamic cell line, were aliquoted in 8x10⁴ in a 24-well plate, and then cultured in an incubator at 37°C containing 5% CO₂ for 24 hours.
배지를 버리고 새로운 배지에 시험물질을 처리한 후, 24시간 배양한 후,After discarding the medium, treating the test substance in a new medium, and culturing for 24 hours,
5mg/ml MTT(Triazol blue Tetrazolium Bromide)용액을 배지에 1/10로 희석하여 넣고, 4시간 동안 배양한 다음, 배양액을 제거하고 DMSO(dimethylsylfoxide) 용액 600ul를 넣고 pipetting하였다. 5mg/ml MTT (Triazol blue Tetrazolium Bromide) solution was diluted 1/10 in the medium, incubated for 4 hours, the culture solution was removed, and 600ul of DMSO (dimethylsylfoxide) solution was added and pipetting.
각 용액 96 well plate에 80ul씩 취하고 Spectrophotometer로 550nm에서 흡광도를 측정하였다. Take 80ul of each solution in a 96-well plate and measure the absorbance at 550nm with a spectrophotometer.
세포 독성의 정도는 배지 자체를 사용한 대조군의 흡광 강도를 기준으로 백분율 표시하였다.The degree of cytotoxicity was expressed as a percentage based on the absorbance intensity of the control group using the medium itself.
cell viability (%) = (시험군의 흡광도/대조군의 흡광도) x 100 (%)cell viability (%) = (absorbance of test group / absorbance of control group) x 100 (%)
실시예 2:신경세포에서의 AChE활성 저해 실험Example 2: AChE activity inhibition experiment in neurons
세포 배양cell culture
시상하부 세포주인 mHypo-42 세포를 24 well dish 배양접시에 접종하였다. 생육 배지로는 Penicillin(100UI/ml), Streptomycin(100ug/ml), 10% FBS(fetal bovine serum)을 함유하는 DMEM(Dulbecco's Modified Eagle's Medium)을 사용했다. 실험기간 동안 세포는 5% CO₂를 포함하는 37℃ incubator에서 배양하였다.The hypothalamic cell line, mHypo-42 cells, was inoculated into a 24-well dish culture dish. As a growth medium, DMEM (Dulbecco's Modified Eagle's Medium) containing Penicillin (100UI/ml), Streptomycin (100ug/ml), and 10% FBS (fetal bovine serum) was used. During the experiment, cells were cultured in an incubator at 37°C containing 5% CO₂.
효소 용액의 제조Preparation of Enzyme Solution
60dish 배양접시에 시상하부 세포주인 mHypo-42 세포를 5x105cells/dish만큼 분주한 후, 5% CO₂를 포함하는 37℃ incubator에서 24시간 배양하였다. After dispensing 5x10 5 cells/dish of mHypo-42 cells, a hypothalamic cell line, in a 60-dish culture dish, they were cultured for 24 hours at 37°C in an incubator containing 5% CO₂.
배지를 버리고 새로운 배지에 실험물질들을 농도별로 처리한 후, 24시간 배양한다. PBS로 세척 후 다시 PBS 1ml을 넣어 scrapper로 세포를 긁어 e-tube에 옮긴 후, Discard the medium, process the test substances in a new medium by concentration, and incubate for 24 hours. After washing with PBS, put 1ml of PBS again, scrape the cells with a scrapper, and transfer them to the e-tube,
4℃에서 7000rpm으로 5분 30초간 원심분리하여 cell pellet을 취하고 0.05% PBS-T를 넣어 voltexing 하여 cell lysis하였다. After centrifugation at 4°C at 7000rpm for 5 minutes and 30 seconds, the cell pellet was taken, and 0.05% PBS-T was added and voltexed for cell lysis.
이 용액을 ice에 30분간 방치하여 세포를 균질화한 다음, 다시 이 용액을 4℃에서 12000rpm으로 5분 30초간 원심분리한 후, 상층액을 취하여 효소액으로 사용하였다.The solution was left on ice for 30 minutes to homogenize the cells, and then the solution was centrifuged again at 12000 rpm at 4°C for 5 minutes and 30 seconds, and the supernatant was taken and used as an enzyme solution.
실험 방법 Experimental method
위 효소 용액 제조 과정으로 만들어진 용액을 96well plate 각 well에 동일한 양을 넣고 0.1M Sodium phosphate buffer(PH 7.0)와 1mM 5,5'-Dithiobis-(2-Nitrobenzoic Acid)(DTNB)을 넣은 후, 10분 pre-incubation을 해준다. 0.5mM 효소기질을 첨가해준 후, 37℃에서 10분 배양한 다음,Put the same amount of the solution prepared in the above enzyme solution preparation process in each well of a 96-well plate, add 0.1M sodium phosphate buffer (PH 7.0) and 1mM 5,5'-Dithiobis-(2-Nitrobenzoic Acid) (DTNB), then 10 Minute pre-incubation. After adding 0.5 mM enzyme substrate, incubated at 37°C for 10 minutes,
412nm에서 Spectrophotometer로 측정하였다. Measurements were made with a Spectrophotometer at 412 nm.
상기 실시예의 실험 결과를 하기에 설명한다.The experimental results of the above examples will be described below.
도 2에서 알 수 있는 바와 같이, 마퀴베리 70% EtOH 추출물을 농도별로 각각 0.03 - 1mg/ml 처리하여 AchE 활성 저해를 확인한 결과, 마퀴베리는 농도가 높아질수록 AchE 활성 저해 또한 높아지는 것을 확인하였다. 특히 1mg/ml에서 거의 76% 정도의 높은 AchE 활성 저해 효과를 보였다.As can be seen from FIG. 2 , the inhibition of AchE activity was confirmed by treating the maquiberry 70% EtOH extract by concentration of 0.03 - 1 mg/ml, respectively. In particular, it showed a high inhibitory effect on AchE activity of about 76% at 1 mg/ml.
또한 마퀴베리 70% EtOH 추출물을 mouse 뇌 시상하부 세포인 mHypo-42 cell에 농도별로 각각 0.0625 - 1mg/ml 처리하여 세포 독성 평가와 AchE 활성 억제 평가를 실험하였다. 도 3에서 알 수 있는 바와 같이,1mg/ml의 농도에서까지도 세포독성을 나타내지 않았으며, 신경세포주에서 또한 확연히 AChE 활성 저해효과를 보였다.In addition, 0.0625 - 1mg/ml of maquiberry 70% EtOH extract was treated in mHypo-42 cells, which are hypothalamic cells in the mouse brain, for each concentration to evaluate cytotoxicity and AchE activity inhibition. As can be seen from FIG. 3 , it did not exhibit cytotoxicity even at a concentration of 1 mg/ml, and showed a marked inhibitory effect on AChE activity in neuronal cell lines.
Claims (12)
상기 마퀴베리 추출물은 (a) 물, (b) 탄소수 1-4의 무수 또는 함수 저급 알코올, (c) 상기 저급 알코올과 물과의 혼합용매, (d) 아세톤, (e) 에틸 아세테이트, (f) 클로로포름, (g) 부틸아세테이트, (h) 1,3-부틸렌글리콜, (i) 헥산 및 (j) 디에틸에테르로 구성된 군으로부터 추출 용매로부터 추출된 것을 특징으로 하는 인지 기능 항상용 식품 조성물.The method of claim 1,
The maquiberry extract is (a) water, (b) anhydrous or hydrated lower alcohol having 1-4 carbon atoms, (c) a mixed solvent of the lower alcohol and water, (d) acetone, (e) ethyl acetate, (f ) chloroform, (g) butyl acetate, (h) 1,3-butylene glycol, (i) hexane and (j) a food composition for cognitive function, characterized in that extracted from the extraction solvent from the group consisting of diethyl ether .
상기 마퀴베리 추출물은 에탄올로부터 추출된 것을 특징으로 하는 인지 기능 항상용 식품 조성물.The method of claim 1,
The maqui berry extract is a food composition for constant cognitive function, characterized in that it is extracted from ethanol.
상기 마퀴베리 추출물은 (a) 물, (b) 탄소수 1-4의 무수 또는 함수 저급 알코올, (c) 상기 저급 알코올과 물과의 혼합용매, (d) 아세톤, (e) 에틸 아세테이트, (f) 클로로포름, (g) 부틸아세테이트, (h) 1,3-부틸렌글리콜, (i) 헥산 및 (j) 디에틸에테르로 구성된 군으로부터 추출 용매로부터 추출된 것을 특징으로 하는 인지 기능 장애 예방 또는 치료용 약학 조성물.5. The method of claim 4,
The maquiberry extract is (a) water, (b) anhydrous or hydrated lower alcohol having 1-4 carbon atoms, (c) a mixed solvent of the lower alcohol and water, (d) acetone, (e) ethyl acetate, (f ) chloroform, (g) butyl acetate, (h) 1,3-butylene glycol, (i) hexane and (j) the prevention or treatment of cognitive dysfunction characterized in that extracted from the extraction solvent from the group consisting of diethyl ether pharmaceutical composition for use.
상기 마퀴베리 추출물은 에탄올로부터 추출된 것을 특징으로 하는 인지 기능 장애 예방 또는 치료용 약학 조성물.5. The method of claim 4,
The maqui berry extract is a pharmaceutical composition for preventing or treating cognitive dysfunction, characterized in that it is extracted from ethanol.
상기 마퀴베리 추출물은 (a) 물, (b) 탄소수 1-4의 무수 또는 함수 저급 알코올, (c) 상기 저급 알코올과 물과의 혼합용매, (d) 아세톤, (e) 에틸 아세테이트, (f) 클로로포름, (g) 부틸아세테이트, (h) 1,3-부틸렌글리콜, (i) 헥산 및 (j) 디에틸에테르로 구성된 군으로부터 추출 용매로부터 추출된 것을 특징으로 하는 아세틸콜린 에스테라제 활성 저해용 조성물.8. The method of claim 7,
The maquiberry extract is (a) water, (b) anhydrous or hydrated lower alcohol having 1-4 carbon atoms, (c) a mixed solvent of the lower alcohol and water, (d) acetone, (e) ethyl acetate, (f Acetylcholine esterase activity, characterized in that it is extracted from the extraction solvent from the group consisting of ) chloroform, (g) butyl acetate, (h) 1,3-butylene glycol, (i) hexane and (j) diethyl ether. inhibitory composition.
상기 마퀴베리 추출물은 에탄올로부터 추출된 것을 특징으로 하는 아세틸콜린 에스테라제 활성 저해용 조성물.8. The method of claim 7,
The composition for inhibiting acetylcholine esterase activity, characterized in that the maquiberry extract is extracted from ethanol.
상기 마퀴베리 추출물은 (a) 물, (b) 탄소수 1-4의 무수 또는 함수 저급 알코올, (c) 상기 저급 알코올과 물과의 혼합용매, (d) 아세톤, (e) 에틸 아세테이트, (f) 클로로포름, (g) 부틸아세테이트, (h) 1,3-부틸렌글리콜, (i) 헥산 및 (j) 디에틸에테르로 구성된 군으로부터 추출 용매로부터 추출된 것을 특징으로 하는 방법.11. The method of claim 10,
The maquiberry extract is (a) water, (b) anhydrous or hydrated lower alcohol having 1-4 carbon atoms, (c) a mixed solvent of the lower alcohol and water, (d) acetone, (e) ethyl acetate, (f ) chloroform, (g) butyl acetate, (h) 1,3-butylene glycol, (i) hexane and (j) diethyl ether extracted from the extraction solvent from the group consisting of.
11. The method of claim 10, wherein the extract is characterized in that the treatment of 0.03 to 1 mg / ml cells.
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