KR20210118492A - A composition for improving memory, cognitive function, or preventing and improving brain neurological diseases - Google Patents
A composition for improving memory, cognitive function, or preventing and improving brain neurological diseases Download PDFInfo
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Abstract
Description
본 발명은 기억력, 인지기능 개선용 또는 뇌신경질환 예방 및 개선용 조성물에 관한 것이다. 보다 상세하게는 우수한 초기 개선활성으로, 초기에 빠른 개선 활성을 나타낼 수 있도록 하는 기억력, 인지기능 개선용 또는 뇌신경질환 예방 및 개선용 조성물에 관한 것이다.The present invention relates to a composition for improving memory, cognitive function, or preventing and improving cranial nerve disease. More particularly, it relates to a composition for improving memory, cognitive function, or preventing and improving cranial nerve disease, which can exhibit rapid improvement activity at an early stage with excellent initial improvement activity.
전 세계적으로 노령인구의 비율이 급격이 증가하고 있는데 최근의 한 분석에 의하면 2050년에는 60세 이상의 인구가 20억 명에 이를 것이라고 한다. 2013년 현재 통계청의 자료를 보면 우리나라의 노령화 지수(15세 미만 인구 대비 65세 이상 노령 인구의 비율)가 83.3%이며 65세 이상의 인구비율이 12.2%라고 한다. 이러한 노령인구의 증가에 따라 노인성 질병이 늘고 있으며 이에 대한 대책도 시급하게 논의되고 있다. 노인성 질병 중에서도 가장 문제가 되고 있는 것은 인지장애인 치매(dementia)라고 할 수 있다. 치매는 뇌기능이 손상되어 기억력, 언어능력, 시공간 파악능력 및 판단력, 그리고 추상적 사고력 등의 인지기능이 지속적이고 전반적으로 떨어지는 것을 의미하여 심한 경우에는 일상생활에 많은 지장이 나타나게 된다. 치매는 일종의 뇌질환으로 그 원인으로서는 알츠하이머병과 혈관성 치매뿐만 아니라 파킨슨병 등의 퇴행성 뇌질환들과 두부외상, 감염성 질환 등 다양한 원인들에 의해 발생되는 것으로 알려져 있다. 따라서 노인인구의 기하급수적 증가와 더불어 급증하고 있는 치매질환을 치료하고 관리하기 위한 노력이 절실하다고 할 수 있다.The proportion of the elderly population is rapidly increasing worldwide, and according to a recent analysis, the number of people aged 60 and over will reach 2 billion by 2050. As of 2013, according to the data of the National Statistical Office, Korea's aging index (the ratio of the population aged 65 and over to the population under 15) was 83.3%, and the proportion of the population aged 65 and over was 12.2%. As the elderly population increases, geriatric diseases are increasing, and countermeasures are urgently discussed. Among the diseases of the elderly, one of the most problematic is cognitive impairment dementia (dementia). Dementia refers to a continuous and overall decline in cognitive functions such as memory, language ability, temporal and spatial understanding and judgment, and abstract thinking ability due to impaired brain function. Dementia is a type of brain disease and is known to be caused by various causes such as Alzheimer's disease and vascular dementia, as well as degenerative brain diseases such as Parkinson's disease, head trauma, and infectious diseases. Therefore, it can be said that efforts to treat and manage dementia diseases, which are rapidly increasing along with the exponential increase in the elderly population, are urgently needed.
대표적인 만성 퇴행성 뇌질환인 치매 (dementia)는 정신적 인지능력과 사회적 행동능력 두 가지에 모두 영향을 미쳐 정상적인 일상생활의 장애를 가져오는 증상복합체로 정의된다. 치매는 발생 원인에 따라 크게 세 가지로, 뚜렷한 원인 없이 인지기능의 악화가 진행되는 알츠하이머병 (Alzheimer’s disease, AD), 반복된 뇌경색 등 뇌혈관 질환에 의한 혈관성 치매 (vascular dementia, VD), 기타 질환에 의한 치매로 분류한다. 뇌혈관성 치매는 동맥경화에 의한 경색이 주원인이므로 혈전용해제 등의 처리에 의해 증상의 개선이 가능하지만, 알츠하이머병은 현재 많은 연구자들이 활발히 연구하고 있음에도 불구하고 발병 원인이 아직 충분히 밝혀지지 않고 있다.Dementia, a representative chronic degenerative brain disease, is defined as a complex of symptoms that affects both mental cognitive ability and social behavioral ability, leading to disturbances in normal daily life. There are three main types of dementia depending on the cause. Alzheimer's disease (AD), in which cognitive function deteriorates without a clear cause, vascular dementia (VD) caused by cerebrovascular diseases such as repeated cerebral infarction, and other diseases classified as dementia caused by Since the main cause of cerebrovascular dementia is infarction caused by arteriosclerosis, symptoms can be improved by treatment with thrombolytic drugs, etc., but the cause of Alzheimer's disease is still not fully elucidated despite active research by many researchers.
지금까지의 연구 결과, 알츠하이머병은 병리학적으로는 대뇌 피질이나 해마에 생기는 뇌 위축 및 뇌 내에 노인반 (senile plaque)이나 신경원섬유다발(neurofibrillary tangle)이 침착되는 것이 특징으로 밝혀졌다(Selkoe DJ, Alzheimer’s disease: Genes, proteins, and therapy, Physiol. Rev., 81, pp.741-766, 2001). 알츠하이머병의 발병 과정을 관찰하면 베타아밀로이드 (β-amyloid, Aβ)라고 하는 단백질이 축적되고, 이어서 치매가 나타남과 동시에 신경원섬유농축체가 축적되는 것이 밝혀졌다. 노인반은 뇌의 대뇌피질과 해마에서 보이는 호은성의 반점 같은 구조로, 그 중심에 아밀로이드섬유가 있고, 그 주위를 변성된 신경세포 돌기가 둘러싸고 있다. 즉, 베타아밀로이드는 알츠하이머병 환자의 뇌에 축적되어 있는 노인반을 구성하는 주요 성분이며, 이 물질의 신경세포에 대한 독성이 알츠하이머병의 주요한 원인일 것으로 생각되고 있다 (Hardy, JA et al., Alzheimer’s disease: The amyloid cascade hypothesis, Science, 256, pp.184-185, 1992).As a result of the research so far, it was found that Alzheimer's disease is pathologically characterized by brain atrophy in the cerebral cortex or hippocampus and the deposition of senile plaques or neurofibrillary tangles in the brain (Selkoe DJ, Alzheimer's). disease: Genes, proteins, and therapy, Physiol. Rev., 81, pp.741-766, 2001). Observing the pathogenesis of Alzheimer's disease, it was found that a protein called β-amyloid (Aβ) was accumulated, followed by the accumulation of neurofibrillary tangles at the same time as dementia appeared. The senile plaque is a sympathetic spot-like structure seen in the cerebral cortex and hippocampus of the brain, with amyloid fibers in the center and degenerated nerve cell projections surrounding it. That is, beta-amyloid is a major component of the senile plaque accumulated in the brain of Alzheimer's disease patients, and its toxicity to nerve cells is thought to be the main cause of Alzheimer's disease (Hardy, JA et al., Alzheimer's disease). disease: The amyloid cascade hypothesis, Science, 256, pp.184-185, 1992).
과도하게 생성된 베타-아밀로이드가 독성을 유발하는 작용기전은 다양하지만 크게 다음 두 가지의 이론으로 질병의 진행을 설명할 수 있다. 첫 번째 이론은, 아밀로이드 플라크가 발생되면 교세포 (glia)에 염증이 생겨, 결국 신경을 손상시키고 공격하는 사이토카인의 생성을 자극하는 등 일련의 염증반응을 유발하게 된다는 것이다. 두 번째 이론은, 활성산소종 (reactive oxygen species, ROS)의 작용에 근거를 두고 있다. 뇌의 95% 이상은 지방으로 구성되어 있으며, 자유라디칼 (free radical)의 공격을 받아 산화된다. 베타-아밀로이드는 응집 (aggregation) 과정을 거쳐 과산화 수소 (hydrogen peroxide), 수퍼옥시드 음이온 (superoxide anion), 히드록시라디칼 (hydroxylradical) 등의 활성 산소종을 형성하며, 이는 높은 반응성으로 인하여 생체 내 거대분자에 영향을 미쳐 궁극적으로 신경세포에서 능동적 세포사멸 (apoptosis)을 유발하게 된다 (Markesbery WR, Oxidative stress hypothesis in Alzheimer’s disease, The amyloid cascade hypothesis, Free Radic. Biol. Med., 23, pp.134-147, 1992).Although the mechanism of action of excessively produced beta-amyloid causing toxicity is diverse, the disease progression can be largely explained by the following two theories. The first theory is that when amyloid plaques develop, glia become inflamed, triggering a series of inflammatory responses that eventually damage nerves and stimulate the production of attacking cytokines. The second theory is based on the action of reactive oxygen species (ROS). More than 95% of the brain is composed of fat and is oxidized under attack by free radicals. Beta-amyloid undergoes aggregation to form reactive oxygen species such as hydrogen peroxide, superoxide anion, and hydroxylradical, which are large in vivo due to their high reactivity. It affects molecules and ultimately leads to active apoptosis in neurons (Markesbery WR, Oxidative stress hypothesis in Alzheimer's disease, The amyloid cascade hypothesis, Free Radic. Biol. Med., 23, pp.134- 147, 1992).
기억 인지 장애는 알츠하이머 질환자들이 처음으로 겪는 증상이며 또한 가장 흔한 증상이다. 알츠하이머병의 초기에 환자들은 최근의 대화나 일의 내용을 자세하게 기억하지 못하는 최근 기억(recent memory) 장애를 겪게 되는데, 이는 해마의 신경세포가 손상되어 최근 기억을 저장하는 기능이 떨어진 데에서 기인한다. 하지만 이 시기에는 먼 과거에 있었던 사건들에 대한 과거 기억(remote long-term memory)은 상대적으로 잘 유지된다. 그러나 병이 점차 진행됨에 따라 장기기억의 저장과 관련된 대뇌피질이 손상되면서 이러한 과거의 기억도 점차 장애를 보이게 된다.Memory and cognitive impairment is the first and most common symptom experienced by people with Alzheimer's disease. In the early stages of Alzheimer's disease, patients suffer from a recent memory disorder that prevents them from remembering the details of recent conversations or events. . However, during this period, the remote long-term memory of events in the distant past is relatively well maintained. However, as the disease progresses, the cerebral cortex related to the storage of long-term memories is damaged, and these past memories are also gradually impaired.
한편, 동맥경화에 이어 발생한 혈전에 의해 뇌동맥이 막혀 조직이 죽게 되는 지역이 해마(hippocampus)와 같은 중요 지역에서 발생하면 치매로 발전하게 되며, 혈관성치매에서 가장 많은 비율을 차지하는 것은 가는 혈관들이 막히거나 또는 혈액공급이 원활하지 못해 발생하는 겉질밑 허혈성 혈관성 치매(subcortical ischemic vascular dementia, SIVD)(전체 혈관성 치매의 35 내지 67 % 차지)이다(Roman et al., Subcortical ischaemic vascular dementia. Lancet Neurol 2002;1:426-436). 겉질밑 허혈성 혈관성치매(SIVD)에서의 손상은 주로 백색질에서 일어나며 이러한 질환을 닮은 동물모델을 만들기 위해 다양한 방법들이 사용되고 있다(Hainsworth & Markus, Do in vivo experimental models reflect human cerebral small vessel disease; A systematic review. J Cerebral Blood Flow & Metabolism 2008;28:1877-1891). 혈관성 치매에 대해서는 백색질을 이루는 희소돌기아교세포(oligodendrocyte)가 혈관성치매가 일어나는 조건에서 세포자살에 의해 죽는다는 것이 밝혀졌으며, 이를 억제하여 치료를 하기 위한 연구가 진행되고 있다.On the other hand, if the area where the cerebral artery is blocked by a blood clot that occurs following atherosclerosis and the tissue is killed occurs in an important area such as the hippocampus, it develops into dementia. or subcortical ischemic vascular dementia (SIVD) (35 to 67% of all vascular dementias), which is caused by insufficient blood supply (Roman et al., Subcortical ischemic vascular dementia. Lancet Neurol 2002;1) :426-436). Injury in subcortical ischemic vascular dementia (SIVD) mainly occurs in the white matter, and various methods are used to make animal models resembling these diseases (Hainsworth & Markus, Do in vivo experimental models reflect human cerebral small vessel disease; A systematic review (J Cerebral Blood Flow & Metabolism 2008;28:1877-1891). For vascular dementia, it has been found that oligodendrocytes constituting the white matter die by apoptosis under conditions in which vascular dementia occurs, and research is underway to suppress it and treat it.
본 발명의 목적은 기억력, 인지기능 개선용 조성물을 제공하기 위한 것이다.An object of the present invention is to provide a composition for improving memory and cognitive function.
본 발명의 목적은 치매, 알츠하이머를 포함하는 뇌신경질환 예방 및 개선용 조성물을 제공하기 위한 것이다.It is an object of the present invention to provide a composition for preventing and improving cranial nerve diseases including dementia and Alzheimer's.
본 발명의 목적은 우수한 초기 활성으로 초기에 빠른 개선효과를 나타낼 수 있도록 하고, 식물 유래 천연 추출물을 사용하여 장기간 복용에 따른 부작용의 문제가 없는 조성물을 제공하기 위한 것이다.It is an object of the present invention to provide a composition that enables rapid improvement in the initial stage with excellent initial activity and does not have a problem of side effects due to long-term administration using a plant-derived natural extract.
본 발명의 목적은 학습능력 및 집중력을 향상시킬 수 있도록 하는 식품 조성물을 제공하기 위함이다.An object of the present invention is to provide a food composition that can improve learning ability and concentration.
상기 목적을 달성하기 위하여, 본 발명의 일 실시예에 따른 기억력 및 인지기능 개선용 조성물은 일년봉 추출물을 포함하는 것일 수 있다.In order to achieve the above object, the composition for improving memory and cognitive function according to an embodiment of the present invention may include an extract of Ilnyeonbong.
상기 기억력 및 인지기능 개선용 조성물은 뉴그린 추출물을 더 포함하는 것일 수 있다.The composition for improving memory and cognitive function may further include a New Green extract.
본 발명의 다른 일 실시예에 따른 뇌신경질환 예방 및 개선용 조성물은 일년봉 추출물을 포함하는 것일 수 있다.The composition for preventing and improving cranial nerve disease according to another embodiment of the present invention may include an extract of one year bong.
상기 뇌신경질환 예방 및 개선용 조성물은 뉴그린 추출물을 더 포함하는 것일 수 있다.The composition for preventing and improving cranial nerve disease may further include a New Green extract.
상기 뇌신경질환 예방 및 개선용 조성물에 있어서, 상기 뇌신경질환은 신경 퇴행성 질환, 허혈 또는 재관류에 의한 질환 및 정신 장애로 구성된 군으로부터 선택된 것이고, 상기 신경 퇴행성 질환은 파킨슨 병, 헌팅턴 병, 알츠하이머 병, 경도인지장애, 노인성 치매, 근위축성 측삭경화증(amyotrophic lateral sclerosis), 척수소뇌성 운동실조증(Spinocerebellar Atrophy), 뚜렛 증후군(Tourette`s Syndrome), 프리드리히 보행실조(Friedrich`s Ataxia), 마차도-조셉 병(Machado-Joseph`s disease), 루이 소체 치매(Lewy Body Dementia), 근육긴장이상(Dystonia), 진행성 핵상 마비(Progressive Supranuclear Palsy) 및 전두측두엽 치매(Frontotemporal Dementia)로 구성된 군으로부터 선택된 것일 수 있다.In the composition for preventing and improving cranial nerve disease, the cranial nerve disease is selected from the group consisting of neurodegenerative diseases, diseases and psychiatric disorders caused by ischemia or reperfusion, and the neurodegenerative diseases are Parkinson's disease, Huntington's disease, Alzheimer's disease, mild Cognitive impairment, senile dementia, amyotrophic lateral sclerosis, Spinocerebellar Atrophy, Tourette's Syndrome, Friedrich's Ataxia, Machado-Joseph's disease ( Machado-Joseph's disease), Lewy Body Dementia, Dystonia, Progressive Supranuclear Palsy and Frontotemporal Dementia may be selected from the group consisting of.
본 발명의 또 다른 일 실시예에 따른 의약품은 상기 조성물을 포함하는 것일 수 있다.A pharmaceutical according to another embodiment of the present invention may include the composition.
본 발명의 또 다른 일 실시예에 따른 식품은 상기 조성물을 포함하는 것일 수 있다.Food according to another embodiment of the present invention may include the composition.
이하, 본 발명을 더욱 상세하게 설명한다.Hereinafter, the present invention will be described in more detail.
본 발명의 일 실시예에 따른 기억력 및 인지기능 개선용 조성물은 일년봉 추출물을 포함하는 것일 수 있다.The composition for improving memory and cognitive function according to an embodiment of the present invention may include an extract of Ilnyeonbong.
본 발명의 다른 일 실시예에 따른 뇌신경질환 예방 및 개선용 조성물은 일년봉 추출물을 포함하는 것일 수 있다.The composition for preventing and improving cranial nerve disease according to another embodiment of the present invention may include an extract of one year bong.
일년봉은 전체에 굵은 털이 있고 곧추 자라 큰 것은 높이 1 m에 달하는 두해살이풀로서, 줄기에 잎은 어긋나게 돌아가며 달리며, 줄기잎은 타원형이며 가장자리에 톱니가 있고, 꽃은 이른 여름에 피기 시작한다. 꽃송이는 지름이 2 cm 정도이며 가지 끝에 산방꽃차례로 달린다. 꽃송이 가장자리는 흰색의 혀꽃이며 한줄로 돌려피며 안쪽은 황색의 작은 통 모양의 꽃이 여러 개 들어있다.Irnyunbong is a biennial herb that has thick hairs and grows upright and grows up to 1 m in height. The inflorescence is about 2 cm in diameter and hangs at the end of the branch in coaxial inflorescences. The edge of the flower cluster is a white tongue flower, which blooms in a single row, and there are several yellow, tube-shaped flowers inside.
다양한 추출용매가 이용될 수 있다. 바람직하게는, 극성 용매 또는 비극성 용매를 이용할 수 있다. 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 및 THF를 포함한다.A variety of extraction solvents may be used. Preferably, a polar solvent or a non-polar solvent may be used. 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 and THF.
보다 용이하게는, 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. 더 용이하게는, 본 발명의 추출물은 물을 일년봉에 처리하여 수득한 것이다.More easily, the extraction solvent used in the present invention is (a) water, (b) an 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 More easily, the extract of the present invention is obtained by treating water with one year rod.
상기 용매의 양은 추출하는 일년봉의 양에 다라 달라질 수 있으며, 바람직하게는 일년봉 중량의 1 배 내지 20배의 부피량(w/v%), 더욱 바람직하게는 5배 내지 10배의 부피량(w/v%)일 수 있다.The amount of the solvent may vary depending on the amount of the annual rod to be extracted, preferably 1 to 20 times the weight of the annual rod (w/v%), more preferably 5 to 10 times the volume (w/v%) ( w/v%).
상기 추출물의 추출온도는 특별히 제한되지 아니하며, 예를 들어 0℃ 내지 120℃일 수 있으며, 바람직하게는 50℃ 내지 100℃일 수 있다. 본 발명의 추출물 추출시간은 특별히 제한되지 아니하며, 예를 들어 1시간 내지 10일일 수 있으며, 바람직하게는 약 3시간 내지 7시간 일 수 있다.The extraction temperature of the extract is not particularly limited, and may be, for example, 0°C to 120°C, preferably 50°C to 100°C. Extraction time of the extract of the present invention is not particularly limited, and may be, for example, 1 hour to 10 days, preferably about 3 hours to 7 hours.
본 발명의 추출물은 공지의 천연물 추출법으로 추출될 수 있다. 예를 들어 냉침추출, 열수추출, 초음파 추출, 환류냉각 추출, 가열 추출법으로 추출할 수 있으며, 바람직하게는 열수추출 또는 환류 냉각 추출법으로 추출할 수 있으며, 1회 내지 10회, 바람직하게는 2회 내지 4회 반복 추출할 수 있다.The extract of the present invention may be extracted by a known natural product extraction method. For example, extraction may be performed by cold extraction, hot water extraction, ultrasonic extraction, reflux cooling extraction, or heating extraction method, preferably by hot water extraction or reflux cooling extraction method, 1 to 10 times, preferably 2 times Extraction can be repeated to 4 times.
또한, 상기 추출물은 여과하여 액상으로 사용할 수 있으며, 바람직하게는 분무건조 또는 동결건조의 건조 공정을 통하여 고형화하여 사용할 수 있다. 더욱 바람직하게는 분무건조 또는 동결건조 전 덱스트린을 혼합하여 건조할 수 있다.In addition, the extract may be filtered and used in a liquid form, preferably, it may be used after being solidified through a drying process of spray drying or freeze-drying. More preferably, it may be dried by mixing dextrin before spray drying or freeze drying.
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, 일년봉 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 일년봉 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 extract of Ilnyeonbong 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 fractions obtained through the purification method are also included in the extract of Ilnyeonbong of the present invention.
상기 일년봉 추출물을 포함하는 경우 인지기능 및 기억력 개선 효과를 나타내도록 할 수 있다.In the case of including the Ilnyeonbong extract, it is possible to exhibit the effect of improving cognitive function and memory.
상기 기억력 및 인지기능 개선용 조성물은 뉴그린 추출물을 더 포함하는 것일 수 있다.The composition for improving memory and cognitive function may further include a New Green extract.
뉴그린은 남유럽과 서유럽의 해안에서 자생하는 배추속 식물이다. 야생의 뉴그린은 이년생식물이며, 수천년간 재배되어 왔다. 뉴그린은 케일(Brassica oleracea Acephala Group), 카이란(Brassica oleracea Alboglabra Group), 꽃양배추(콜리플라워, 브로코플라워, Brassica oleracea Botrytis Group), 양배추(적채, Brassica oleracea Capitata Group), 방울양배추(brussels sprout, Brassica oleracea Gemmifera Group), 콜라비(Brassica oleracea Gongylodes Group) 및 브로콜리(Brassica oleracea Italica Group)의 일곱 가지 품종군으로 나뉜다.New green is a genus Brassica native to the coasts of southern and western Europe. Wild newgreens are biennials and have been cultivated for thousands of years. New greens include kale (Brassica oleracea Acephala Group), cayenne (Brassica oleracea Alboglabra Group), cauliflower (cauliflower, brocoflower, Brassica oleracea Botrytis Group), cabbage (red greens, Brassica oleracea Capitata Group), Brussels sprouts, It is divided into seven cultivars: oleracea Gemmifera Group), kohlrabi (Brassica oleracea Gongylodes Group) and broccoli (Brassica oleracea Italica Group).
상기 뉴그린 추출물을 더 포함하는 경우 인지기능 및 기억력 개선 효과가 보다 우수할 수 있다.When the New Green extract is further included, the effect of improving cognitive function and memory may be more excellent.
바람직하게 상기 기억력 및 인지기능 개선용 조성물은 일년봉 추출물 100 중량부에 대하여 뉴그린 추출물이 10 내지 5000 중량부로 혼합되는 것일 수 있다. 상기 범위에 의하는 경우 각 추출물의 혼합에 따라 기억력 및 인지기능 개선효과가 보다 증진되는 효과를 나타낼 수 있다.Preferably, the composition for improving memory and cognitive function may be one in which the New Green extract is mixed in an amount of 10 to 5000 parts by weight based on 100 parts by weight of the Ilnyeonbong extract. According to the above range, the effect of improving memory and cognitive function may be more enhanced according to the mixing of each extract.
더 바람직하게 상기 기억력 및 인지기능 개선용 조성물은 일년봉 추출물 100 중량부에 대하여 뉴그린 추출물이 400 내지 500 중량부로 포함되는 것일 수 있다. 상기 범위에 의하는 경우 상호작용에 의한 상승효과가 나타날 뿐만 아니라, 각 추출물을 단독으로 사용하는 경우와 달리 초기 빠른 개선 활성이 나타나는 점을 확인할 수 있다. 이는 각 추출물에 포함된 유효물질이 상기 범위에서 상호 작용으로 상승효과가 나타나고, 빠른 활성으로 투여 초기 인지기능 및 기억력 개선 효과가 나타나는 것으로 볼 수 있다.More preferably, the composition for improving memory and cognitive function may include 400 to 500 parts by weight of the New Green extract based on 100 parts by weight of the Ilnyeonbong extract. In the case of the above range, it can be confirmed that not only a synergistic effect by interaction appears, but also the initial rapid improvement activity appears unlike the case of using each extract alone. It can be seen that the active substances contained in each extract exhibit a synergistic effect by interaction within the above range, and the effect of improving cognitive function and memory at the initial stage of administration due to rapid activity.
본 발명의 다른 일 실시예에 따른 뇌신경질환 예방 및 개선용 조성물은 일년봉 추출물을 포함하는 것일 수 있다.The composition for preventing and improving cranial nerve disease according to another embodiment of the present invention may include an extract of one year bong.
상기 일년봉 추출물을 포함하는 경우 뇌신경질환에 대한 예방 및 개선효과를 나타낼 수 있다.In the case of including the extract of one year bong, it may exhibit a preventive and ameliorating effect on cranial nerve diseases.
상기 뇌신경질환 예방 및 개선용 조성물은 뉴그린 추출물을 더 포함하는 것일 수 있다.The composition for preventing and improving cranial nerve disease may further include a New Green extract.
상기 뉴그린 추출물을 더 포함하는 경우 뇌신경질환에 대한 예방 및 개선효과가 증진될 수 있다.When the New Green extract is further included, the prevention and improvement effect on cranial nerve diseases can be enhanced.
바람직하게 상기 뇌신경질환 예방 및 개선용 조성물은 일년봉 추출물 100 중량부에 대하여 뉴그린 추출물이 10 내지 5000 중량부로 혼합되는 것일 수 있다. 상기 범위에 의하는 경우 각 추출물의 혼합에 따라 뇌신경질환에 대한 예방 및 개선효과가 보다 향상될 수 있다.Preferably, the composition for preventing and improving cranial nerve disease may be one in which the New Green extract is mixed in an amount of 10 to 5000 parts by weight based on 100 parts by weight of the annual extract. When according to the above range, the prevention and improvement effect for cranial nerve diseases may be further improved according to the mixing of each extract.
더 바람직하게 상기 뇌신경질환 예방 및 개선용 조성물은 일년봉 추출물 100 중량부에 대하여 뉴그린 추출물이 400 내지 500 중량부로 포함되는 것일 수 있다. 상기 범위에 의하는 경우 상호작용에 의한 상승효과가 나타날 뿐만 아니라, 각 추출물을 단독으로 사용하는 경우와 달리 초기 빠른 개선 활성이 나타나는 점을 확인할 수 있다. 이는 각 추출물에 포함된 유효물질이 상기 범위에서 상호 작용으로 상승효과가 나타나고, 빠른 활성으로 투여 초기에 상기 뇌신경질환 예방 및 개선용 효과를 나타내게 하는 것으로 볼 수 있다.More preferably, the composition for preventing and improving cranial nerve disease may include 400 to 500 parts by weight of the New Green extract based on 100 parts by weight of the annual extract. In the case of the above range, it can be confirmed that not only a synergistic effect by interaction appears, but also the initial rapid improvement activity appears unlike the case of using each extract alone. It can be seen that the active substances contained in each extract exhibit a synergistic effect by interaction in the above range, and exhibit the effect for preventing and improving the cranial nerve disease at the initial stage of administration due to rapid activity.
보다 바람직하게 상기 기억력 및 인지기능 개선용 조성물 또는 상기 뇌신경질환 예방 및 개선용 조성물은 일년봉 추출물을 포함하고, 상기 일년봉 추출물 100 중량부에 대하여 뉴그린 추출물이 400 내지 500 중량부; 엉겅퀴 추출물 40 내지 80 중량부 및 산골취 추출물 1 내지 3 중량부를 포함하는 것일 수 있다.More preferably, the composition for improving memory and cognitive function or the composition for preventing and improving cranial nerve disease comprises an extract of ilyeongbong, 400 to 500 parts by weight of New Green extract based on 100 parts by weight of the ilanbong extract; It may include 40 to 80 parts by weight of the milk thistle extract and 1 to 3 parts by weight of the sangoschi extract.
상기 범위에 의하는 경우 기억력 및 인지기능 개선 효과와, 뇌신경질환 예방 및 개선 효과가 크게 향상될 뿐만 아니라 투여 초기에 아주 빠르게 효과가 나타날 수 있다. 따라서 적은 함량을 사용하면서도 빠른 개선 효과를 나타내게 할 수 있다.In the case of the above range, the effect of improving memory and cognitive function and the prevention and improvement of cranial nerve disease are greatly improved, and the effect can appear very quickly at the beginning of administration. Therefore, it is possible to exhibit a rapid improvement effect while using a small amount.
상기 엉겅퀴는 전체가 털로 덮여 있는 여러해살이풀로서 윗부분에서 약간의 가지를 치며 곧추 자라 큰 것은 1 m 정도에 달한다. 잎은 긴 타원형 모양이며 가장자리에 크고 작은 가시가 있다. 자주색 또는 적색 꽃이 한 여름에 가지 끝에 한 송이씩 위를 향해 핀다. 한 송이 꽃 안에는 수백 개의 통 모양으로 생긴 작은 꽃이 들어 있으며 열매에 털이 달려 있으며 성숙하면 바람에 날려 번식한다. The thistle is a perennial herb covered with hairs, branching a little at the top, and growing upright, and a large one reaches about 1 m. The leaves are long oval in shape and have large and small thorns on the edge. Purple or red flowers bloom upwards one at the end of a branch in midsummer. Each flower contains hundreds of small, barrel-shaped flowers, with hairs on the fruit.
상기 산골취는 쌍떡잎식물 초롱꽃목 국화과의 여러해살이풀로서, 깊은 산에서 자라며, 줄기는 곧게 서고 윗부분에서 가지를 내기도 한다. 잎의 밑동이 줄기로 흘러서 줄기의 날개가 되며 뿌리에 달린 잎과 밑부분에 달린 잎은 꽃이 필 때 진다. 줄기에 달린 잎은 어긋나고 바소꼴이거나 타원 모양 바소꼴로서 길이 12 내지 15cm이다.The mountain chrysanthemum is a dicotyledonous perennial plant of the Asteraceae family of the order Asteraceae, which grows in a deep mountain, and the stem stands upright and branches out at the upper part. The base of the leaf flows into the stem and becomes the wing of the stem, and the leaf attached to the root and the leaf attached to the lower part fall when the flower blooms. The leaves on the stem are alternate phyllotaxis and are lanceolate or elliptical lanceolate, and are 12 to 15 cm long.
상기 뇌신경질환 예방 및 개선용 조성물에 있어서, 상기 뇌신경질환은 신경 퇴행성 질환, 허혈 또는 재관류에 의한 질환 및 정신 장애로 구성된 군으로부터 선택된 것이고, 상기 신경 퇴행성 질환은 파킨슨 병, 헌팅턴 병, 알츠하이머 병, 경도인지장애, 노인성 치매, 근위축성 측삭경화증(amyotrophic lateral sclerosis), 척수소뇌성 운동실조증(Spinocerebellar Atrophy), 뚜렛 증후군(Tourette`s Syndrome), 프리드리히 보행실조(Friedrich`s Ataxia), 마차도-조셉 병(Machado-Joseph`s disease), 루이 소체 치매(Lewy Body Dementia), 근육긴장이상(Dystonia), 진행성 핵상 마비(Progressive Supranuclear Palsy) 및 전두측두엽 치매(Frontotemporal Dementia)로 구성된 군으로부터 선택된 것일 수 있다.In the composition for preventing and improving cranial nerve disease, the cranial nerve disease is selected from the group consisting of neurodegenerative diseases, diseases and psychiatric disorders caused by ischemia or reperfusion, and the neurodegenerative diseases are Parkinson's disease, Huntington's disease, Alzheimer's disease, mild Cognitive impairment, senile dementia, amyotrophic lateral sclerosis, Spinocerebellar Atrophy, Tourette's Syndrome, Friedrich's Ataxia, Machado-Joseph's disease ( Machado-Joseph's disease), Lewy Body Dementia, Dystonia, Progressive Supranuclear Palsy and Frontotemporal Dementia may be selected from the group consisting of.
본 발명의 또 다른 일 실시예에 따른 의약품은 상기 조성물을 포함하는 것일 수 있다.A pharmaceutical according to another embodiment of the present invention may include the composition.
본 발명의 의약품 또는 약제학적 조성물은 경구 또는 비경구 투여할 수 있으며, 바람직하게는 경구 투여 방식으로 적용된다. 본 발명의 의약품에 대한 적합한 투여량은 제제화 방법, 투여방식, 환자의 연령, 체중, 성, 병적 상태, 음식, 투여 시간, 투여 경로, 배설 속도 및 반응 감응성과 같은 요인들에 의해 다양하게 처방될 수 있다. 본 발명의 의약품에 대한 바람직한 투여량은 성인 기준으로 0.001-100 ㎎/kg 범위 내이다.The pharmaceutical or pharmaceutical composition of the present invention may be administered orally or parenterally, and is preferably applied by oral administration. A suitable dosage for the drug of the present invention may be prescribed in various ways depending on factors such as formulation method, administration mode, age, weight, sex, pathological condition, food, administration time, administration route, excretion rate, and response sensitivity of the patient. can A preferred dosage for the pharmaceutical of the present invention is within the range of 0.001-100 mg/kg for adults.
본 발명의 약제학적 조성물은 당해 발명이 속하는 기술분야에서 통상의 지식을 가진 자가 용이하게 실시할 수 있는 방법에 따라, 약제학적으로 허용되는 담체 및/또는 부형제를 이용하여 제제화함으로써 단위 용량 형태로 제조되거나 또는 다용량 용기 내에 내입시켜 제조될 수 있다. 이때 제형은 오일 또는 수성매질중의 용액, 현탁액, 시럽제 또는 유화액 형태이거나 엑스 제, 산제, 분말제, 과립제, 정제 또는 캅셀제 형태일 수도 있으며, 분산제 또는 안정화제를 추가적으로 포함할 수 있다.The pharmaceutical composition of the present invention is prepared in unit dosage form by formulating using a pharmaceutically acceptable carrier and/or excipient according to a method that can be easily carried out by a person of ordinary skill in the art to which the present invention pertains. or may be prepared by incorporation into a multi-dose container. In this case, the formulation may be in the form of a solution, suspension, syrup, or emulsion in oil or aqueous medium, or may be in the form of an extract, powder, powder, granule, tablet or capsule, and may additionally include a dispersant or stabilizer.
본 발명의 또 다른 일 실시예에 따른 식품은 상기 조성물을 포함하는 것일 수 있다.Food according to another embodiment of the present invention may include the composition.
본 발명의 조성물이 식품으로로 제조되는 경우, 유효성분으로서 일년봉 추출물뿐 만 아니라, 식품 제조 시에 통상적으로 첨가되는 성분을 포함하며, 예를 들어, 단백질, 탄수화물, 지방, 영양소, 조미제 및 향미제를 포함한다. 상술한 탄수화물의 예는 모노사카라이드, 예를 들어, 포도당, 과당 등; 디사카라이드, 예를 들어 말토스, 슈크로스, 올리고당 등; 및 폴리사카라이드, 예를 들어 덱스트린, 사이클로덱스트린 등과 같은 통상적인 당 및 자일리톨, 소르비톨, 에리트리톨 등의 당알콜이다. 향미제로서 천연 향미제 [타우마틴, 스테비아 추출물(예를 들어 레바우디오시드 A, 글리시르히진 등]) 및 합성 향미제(사카린, 아스파르탐 등)를 사용할 수 있다.When the composition of the present invention is prepared as food, it includes not only the annual extract as an active ingredient, but also ingredients commonly added during food production, for example, proteins, carbohydrates, fats, nutrients, seasonings and Contains flavoring agents. Examples of the above-mentioned carbohydrates include monosaccharides such as glucose, fructose and the like; disaccharides such as maltose, sucrose, oligosaccharides and the like; and polysaccharides, for example, conventional sugars such as dextrin, cyclodextrin, and the like, and sugar alcohols such as xylitol, sorbitol, and erythritol. As flavoring agents, natural flavoring agents [taumatine, stevia extract (eg, rebaudioside A, glycyrrhizin, etc.)) and synthetic flavoring agents (saccharin, aspartame, etc.) can be used.
본 발명의 식품 조성물은 기능성 식품(functional food), 영양 보조제(nutritional supplement), 건강식품(health food) 및 식품 첨가제(food additives) 등의 모든 형태를 포함한다. 상기 유형의 식품 조성물은 당업계에 공지된 통상적인 방법에 따라 다양한 형태로 제조할 수 있다.The food composition of the present invention includes all types of functional foods, nutritional supplements, health foods, and food additives. Food compositions of this type can be prepared in various forms according to conventional methods known in the art.
예를 들면, 건강식품으로는 일년봉 혼합추출물 자체를 차, 주스 및 드링크의 형태로 제조하여 음용하도록 하거나, 과립화, 캡슐화 및 분말화하여 섭취할 수 있다. 또한, 본 발명의 일년봉 혼합추출물과 스트레스 예방 또는 개선의 효과가 있다고 알려진 공지의 활성 성분 또는 기억력 감퇴에 대하여 개선 효과가 있다고 알려진 공지의 활성 성분과 함께 혼합하여 조성물의 형태로 제조할 수 있다.For example, as a health food, the mixed extract of one year bong itself can be prepared and consumed in the form of tea, juice, and drink, or it can be consumed by granulation, encapsulation, and powder. In addition, it can be prepared in the form of a composition by mixing the mixed extract of the present invention with a known active ingredient known to be effective in preventing or improving stress or an active ingredient known to be effective in improving memory loss.
본 발명은 기억력, 인지기능 개선용 조성물을 제공한다.The present invention provides a composition for improving memory and cognitive function.
본 발명은 치매, 알츠하이머를 포함하는 뇌신경질환 예방 및 개선용 조성물을 제공한다.The present invention provides a composition for preventing and improving cranial nerve diseases including dementia and Alzheimer's.
본 발명은 우수한 초기 활성으로 초기에 빠른 개선효과를 나타낼 수 있도록 하고, 식물 유래 천연 추출물을 사용하여 장기간 복용에 따른 부작용의 문제가 없는 조성물을 제공한다.The present invention provides a composition capable of exhibiting a rapid improvement effect in the early stage with excellent initial activity, and having no problem of side effects due to long-term administration using a plant-derived natural extract.
본 발명은 학습능력 및 집중력을 향상시킬 수 있도록 하는 식품 조성물을 제공한다.The present invention provides a food composition that can improve learning ability and concentration.
도 1은 본 발명의 일 실시예에 따른 조성물의 신경세포보호활성 실험 결과에 관한 것이다.
도 2는 본 발명의 일 실시예에 따른 조성물의 신경세포보호활성 실험 결과에 관한 것이다.
도 3은 본 발명의 일 실시예에 따른 조성물의 파킨슨병 예방 효과 실험 결과에 관한 것이다.
도 4는 본 발명의 일 실시예에 따른 조성물의 파킨슨병 예방 효과 실험 결과에 관한 것이다.
도 5는 본 발명의 일 실시예에 따른 조성물의 인지기능 및 기억력 개선 효과 실험에 관한 것이다.1 relates to a neuroprotective activity test result of a composition according to an embodiment of the present invention.
Figure 2 relates to the neuroprotective activity test results of the composition according to an embodiment of the present invention.
Figure 3 relates to the experimental results of the Parkinson's disease prevention effect of the composition according to an embodiment of the present invention.
4 is related to the experimental results of the Parkinson's disease prevention effect of the composition according to an embodiment of the present invention.
5 relates to an experiment on the cognitive function and memory improvement effect of the composition according to an embodiment of the present invention.
이하, 본 발명이 속하는 기술 분야에서 통상의 지식을 가진 자가 용이하게 실시할 수 있도록 본 발명의 실시예에 대하여 상세히 설명한다. 그러나 본 발명은 여러 가지 상이한 형태로 구현될 수 있으며 여기에서 설명하는 실시예에 한정되지 않는다.Hereinafter, embodiments of the present invention will be described in detail so that those of ordinary skill in the art can easily carry out the present invention. However, the present invention may be embodied in many different forms and is not limited to the embodiments described herein.
[제조예: 추출물의 제조 및 혼합][Preparation Example: Preparation and mixing of extract]
1. 일년봉 추출물의 제조1. Preparation of one-year-old extract
일년봉을 분쇄하여 분말로 제조한 뒤 건조하였다. 이후 열수추출 하고 여과 및 진공 농축하여 일년봉 추출물(E1)을 제조하였다.Iryeonbong was pulverized to make a powder, and then dried. After hot-water extraction, filtration and vacuum concentration to prepare the Ilnyeonbong extract (E1).
2. 기타 추출물의 제조2. Preparation of other extracts
뉴그린 추출물(E2), 엉겅퀴 추출물(E3) 및 산골취 추출물(E4)을 위 일년봉 추출물과 동일한 방법으로 제조하였다.New green extract (E2), milk thistle extract (E3), and mountain chrysanthemum extract (E4) were prepared in the same manner as the above onenyeonbong extract.
3. 혼합 추출물의 제조3. Preparation of Mixed Extracts
각 추출물의 혼합에 따른 상승효과를 확인하기 위하여 하기의 [표 1]과 같은 조성으로 각 추출물을 혼합하였다.In order to confirm the synergistic effect of mixing each extract, each extract was mixed with the composition shown in [Table 1] below.
(단위: 중량부)(Unit: parts by weight)
[실험예 1: 신경세포보호 효과 실험][Experimental Example 1: Neuroprotective effect test]
사람 신경모세포종(neuroblastoma cell)인 SK-N-SH 세포를 96-well(Nunc, Slangerup, Denmark)에 15,000 cells/well의 밀도로 씨딩(seeding)하고 24시간 동안 배양하였다. 세포 배양액을 1% FBS가 들어있는 DMEM으로 갈아주고 2시간 동안 추가로 배양하였다. 배양된 세포에 뉴그린 추출물을 10 농도가 되도록 첨가하고 음성대조군으로는 인산염완충식염수(pH 7.4)를 동일한 양 첨가하여 2시간을 추가로 배양하였다. 이후 각 군의 배양액에 Aβ1-42를 20 이 되도록 첨가하고 2시간을 추가로 배양하였다. Aβ1-42처리에 대한 음성대조군으로는 인산염완충식염수(pH 7.4)를 동일한 양으로 첨가하여 배양하였다.SK-N-SH cells, which are human neuroblastoma cells, were seeded at a density of 15,000 cells/well in 96-wells (Nunc, Slangerup, Denmark) and cultured for 24 hours. The cell culture medium was replaced with DMEM containing 1% FBS and further cultured for 2 hours. New Green extract was added to the cultured cells to a concentration of 10, and as a negative control, the same amount of phosphate buffered saline (pH 7.4) was added and incubated for additional 2 hours. Thereafter, Aβ 1-42 was added to the culture medium of each group so as to be 20, and incubated for an additional 2 hours. As a negative control for Aβ 1-42 treatment, phosphate buffered saline (pH 7.4) was added in the same amount and cultured.
이후 alamarblue(Serotec, Oxford, UK)를 10 ㎕ 처리한 후 3시간 배양하고, ELISA 리더기(Molecular Divices, Sunnycale, CA, USA)를 이용하여 570 ㎚에서 흡광도를 측정하였다. 배경 흡광도(blank count)는 600 ㎚에서 측정한 값을 사용하였다.Thereafter, alamarblue (Serotec, Oxford, UK) was treated with 10 μl, incubated for 3 hours, and absorbance was measured at 570 nm using an ELISA reader (Molecular Divices, Sunnycale, CA, USA). Background absorbance (blank count) was a value measured at 600 nm.
E1 내지 E4의 신경세포 보호 효과를 확인하기 위하여, 신경모세포종에 베타 아밀로이드 단백질(Aβ)을 첨가하였다. 신경모세포종에 베타 아밀로이드단백질(Aβ)을 첨가로 어포토시스 형태의 세포사멸이 일어났다. 한편, E1 및 E2에 의하는 경우 베타 아밀로이드 단백질(Aβ)을 처리하지 않은 것(non)과 유사한 정도의 세포 생존을 확인할 수 있었다.In order to confirm the neuroprotective effect of E1 to E4, beta amyloid protein (Aβ) was added to neuroblastoma. The addition of beta-amyloid protein (Aβ) to neuroblastoma caused apoptosis in the form of apoptosis. On the other hand, in the case of E1 and E2, it was possible to confirm cell survival similar to that of the non-treated beta-amyloid protein (Aβ).
한편, 혼합 추출물의 경우 T2 내지 T4 범위에서 일정한 상승효과를 확인할 수 있었으며, 특히 T7 내지 T9의 경우 추가적인 상승효과로 90% 내외의 상당히 우수한 세포 생존을 확인할 수 있었다.On the other hand, in the case of the mixed extract, it was possible to confirm a certain synergistic effect in the range of T2 to T4, and in particular, in the case of T7 to T9, it was possible to confirm a fairly excellent cell survival of about 90% with an additional synergistic effect.
[실험예 2: 파킨슨병 예방 효과 실험][Experimental Example 2: Parkinson's disease prevention effect test]
파킨슨병 유발 약물로 널리 사용되고 있는 수산화도파민 (6-hydroxydopamine, 6-OHDA)을 백서 뇌의 편측 선조체(striatum)에 주입하여 도파민 신경세포의 점진적 퇴행변성을 일으키는 Joo 등의 방법(Joo WS et al.,Neuroreport, 9(18), 4123-4126, 1998)의 방법을 이용하여 동물모델을 다음과 같이 제작하였다.The method of Joo et al. (Joo WS et al. , Neuroreport, 9(18), 4123-4126, 1998), an animal model was prepared as follows.
체중 200-250 g의 수컷 스프라그-돌리계의 백서에 케타민(100 ㎎/㎏)과 자일라진(50 ㎎/㎏)을 복강으로 주사하여 마취시켰다. 마취동물을 뇌정위수술기구 (stereotaxic frame, David Kopf, USA)를 이용하여 두개골을 천공하고 대조군 (sham group)에는 0.2 ㎎/㎖ 아스코르빈산을 사용하고, 변병군(lesioned group)에는 수산화도파민(20 ㎍/5 ㎕ free base in 0.2 ㎎/㎖ 아스코르빈산)을 오른쪽 선조체에 해밀턴 주사기(10㎕, 26G 바늘)를 사용하여 분당 1 ㎕의 속도로 주입하였다(Paxinos et al., J. Neurosci. Methods. 3(2), 129-249, 1980). 약물 주입 후 5분 동안 바늘을 그대로 두고, 분당 1 ㎜의 속도로 바늘을 빼낸 후 절개부위를 봉합하였다. 6-OHDA 투여 3일 전부터 실시예 1에서 제조한 뉴그린 추출물을 생리식염수에 희석하여 50 ㎎/㎏ 용량으로 3일간 매일 1회 복강주사로 투여하였다.A male Sprague-Dawley white paper weighing 200-250 g was anesthetized by intraperitoneal injection of ketamine (100 mg/kg) and xylazine (50 mg/kg). Anesthetized animals were perforated into the skull using a stereotaxic surgical instrument (stereotaxic frame, David Kopf, USA), 0.2 mg/ml ascorbic acid was used for the control group (sham group), and dopamine hydroxide (hydroxylated group) was used for the lesioned group. 20 μg/5 μl free base in 0.2 mg/ml ascorbic acid) was injected into the right striatum using a Hamilton syringe (10 μl, 26G needle) at a rate of 1 μl per minute (Paxinos et al., J. Neurosci. Methods 3(2), 129-249, 1980). After injecting the drug, the needle was left there for 5 minutes, the needle was withdrawn at a rate of 1 mm per minute, and the incision was sutured. From 3 days before 6-OHDA administration, the New Green extract prepared in Example 1 was diluted in physiological saline and administered by intraperitoneal injection once daily for 3 days at a dose of 50 mg/kg.
한편, 수산화도파민을 이용하여 제작한 파킨슨병 동물 모델에서 시간 경과에 따른 행동학적 변화를 병변 제작 후 14일에 아포몰핀(0.5 ㎎/㎏)을 뒷목에 피하 주사하고, 60분 동안 일측성 회전반응을 측정하였다.On the other hand, behavioral changes over time in an animal model of Parkinson's disease prepared using hydroxydopamine were subcutaneously injected into the back of the neck on the 14th day after lesion preparation, followed by a unilateral rotational reaction for 60 minutes. was measured.
본 실험은 도파민성 신경 세포가 사멸되어 선조체 내 도파민의 농도가 감소되면, 선조체 내 도파민 수용체의 과민성이 유발되어 아포몰핀은 도파민 수용체에 효현제로 작용하여 과민성이 유발된 선조체를 과도하게 흥분시킴으로써 동물은 손상측과 반대방향으로 회전운동을 하게 되는 원리를 이용한 것이다(Ungerstedt, Brain Res. 24, 485-493, 2970). 회전운동은 Ungerstedt의 상기 논문에 기재된 자동화된 회전운동 측정기(rotometer)를 이용하였으며, 각 회전수는 [순 회전수(net turns) = 비병변측 회전수(contralateral) - 병변측 회전수(ipsilateral)]로 산출하였다.In this experiment, when dopaminergic neurons die and the concentration of dopamine in the striatum decreases, hypersensitivity of the dopamine receptors in the striatum is induced, and apomorphine acts as an agonist on the dopamine receptors. It uses the principle of rotating in the opposite direction to the injured side (Ungerstedt, Brain Res. 24, 485-493, 2970). Rotational motion was performed using the automated rotometer described in the above paper by Ungerstedt, and each number of rotations was [net turns = contralateral - ipsilateral]. ] was calculated.
도 3을 참조하면, 0.2 ㎎/㎖ 아스코르빈산을 선조체에 투여한 정상 대조군의 일측성 순 회전수는 큰 변화가 없었지만, 수산화도파민만을 투여한 병변 대조군에서는 일측성 순회전수가 유의하게 증가되었다. 한편, E1 및 E2의 경우 병변 대조군에 비하여 일측성 순 회전수가 감소하는 점을 확인할 수 있다Referring to FIG. 3 , there was no significant change in the unilateral net rotation in the normal control group administered with 0.2 mg/ml ascorbic acid to the striatum, but the unilateral rotation in the lesion control group administered only with hydroxydopamine was significantly increased. On the other hand, in the case of E1 and E2, it can be seen that the unilateral net rotation is decreased compared to the lesion control group.
또한, 혼합 추출물의 경우 T2 내지 T4 범위에서 E1 및 E2를 각각 사용하거나 단순히 조합하는 경우에 비하여 일정한 상승효과가 나타나는 점을 확인할 수 있었다. 특히 T7 내지 T9의 경우 추가적인 상승효과로서 병변 대조군에 비해 일측성 순 회전수가 상당히 감소하는 점을 확인할 수 있었다. 이를 통하여 본 발명에 의하는 경우 파킨슨병 억제 효과가 있음을 확인하였다.In addition, in the case of the mixed extract, it was confirmed that a certain synergistic effect appeared in the range of T2 to T4 compared to the case of using each of E1 and E2 or simply combining them. In particular, in the case of T7 to T9, as an additional synergistic effect, it was confirmed that the unilateral net rotation was significantly reduced compared to the lesion control group. Through this, it was confirmed that there is an inhibitory effect on Parkinson's disease according to the present invention.
[실험예 3: 인지기능 및 기억력 개선효과 실험][Experimental Example 3: Cognitive function and memory improvement effect experiment]
실험 동물은 웅성 백서 (Sprague Dawley, 140 내지 180 g, 대한실험동물센터)로서, 이들은 일정한 환경 (실내온도 25±1℃, 상대습도 60±10%)에서 일주일 동안 하나의 사육 상자 당 4 마리씩 넣어 물은 제한 없이 제공하였으며, 이때, 몸무게의 80%를 유지하도록 제한 급식을 실시하였다. 본 실험에서는 총 50 마리를 사용하였다. 훈련 3일 전부터 5분씩 미로에 적응시켜 검사를 진행하였다.Experimental animals were male white paper (Sprague Dawley, 140 to 180 g, Korea Laboratory Animal Center), and they were put in a constant environment (room temperature 25±1℃,
총 세 개의 통로(왼쪽, 오른쪽, 중앙부)가 있으며, 각 통로 입구는 실험자가 동물의 출입을 통제할 수 있도록 칸막이를 설치한 "ㅠ"자 모양의 미로를 준비하였다.There are a total of three passages (left, right, and central), and at the entrance to each passage, a “ㅠ”-shaped maze with partitions installed so that the experimenter can control the entrance of animals was prepared.
첫 시행에서는 출발 상자에 1분간 적응시켰다. 첫 시행은 '강제 선택 시행'으로, 칸막이로 한쪽 통로를 막아놓고 반대편 통로에 동물이 들어가면 칸막이로 후방을 막았다. 동물의 사지가 통로 입구를 통과하면 동물이 들어간 것으로 간주하였다. 60초간 동물이 해당 통로에서 먹이를 먹도록 하였다.In the first trial, they were acclimatized to the starting box for 1 minute. The first trial was a 'compulsory selection trial', in which one passage was blocked with a partition, and when an animal entered the other passage, the rear was blocked with a partition. Animals were considered to have entered if their limbs passed through the passage entrance. Animals were allowed to feed in the passage for 60 seconds.
다음 시행부터는 '자유 선택 시행'으로 동물이 출발상자에서 출발하여 자유롭게 통로의 방향(왼쪽 혹은 오른쪽)을 선택하도록 하였다. 동물은 바로 이전의 시행에서 들어갔던 통로와 반대편 통로로 들어갔을 경우에만 먹이 보상을 하였다.From the next trial, the 'free choice trial' allowed the animal to freely select the direction of the passage (left or right) starting from the starting box. Animals were rewarded with food only when they entered the passageway opposite the passageway they entered in the immediately preceding trial.
시행 간격은 5초 및 20초로 지연 시간(delay)를 두고 구성되며, 매 시행의 제한시간(cut-off time)은 60초로 하였다. 동물이 강화가 주어지는 통로에 정확하게 들어간 횟수와 통로까지 들어가는데 걸린 시간을 측정하였다. 하루에 10 시행식 9일 동안 동일한 절차를 수행하여 평가하였다.The trial interval was configured with a delay of 5 seconds and 20 seconds, and the cut-off time of each trial was 60 seconds. The number of times the animal correctly entered the passageway to which the reinforcement was given and the time it took to enter the passageway were measured. The same procedure was performed for 9 days with 10 trials per day and evaluated.
한편, 본 발명의 제조방법에 따라 제조된 E1, E2 및 T1 내지 T10을 100 ㎎/㎖의 용액으로 제조하여 구강 투여하였다. 모든 시료들은 증류수에 용해하여 구강 투여하였다.Meanwhile, E1, E2, and T1 to T10 prepared according to the preparation method of the present invention were prepared in a solution of 100 mg/ml and administered orally. All samples were dissolved in distilled water and administered orally.
E1, E2 및 T1 내지 T10을 투여한 군에 대해 T-maze 실험을 진행한 결과를 하기의 [도 5]에 나타내었다. [도 5]는 시행 간격을 5초로 구성하여 실험을 진행한 것으로, 9일 간의 훈련 기간 동안 성능이 점차적으로 향상되었다.The results of the T-maze experiment for the groups administered with E1, E2, and T1 to T10 are shown in [Fig. 5] below. [Fig. 5] shows that the experiment was conducted with the trial interval of 5 seconds, and the performance was gradually improved during the 9-day training period.
한편, E1 및 E2의 혼합에 의하는 경우 전반적으로 상승효과가 나타나는 점을 확인할 수 있으며, 특히 T2 내지 T4에 의하는 경우 초기 개선 활성이 높아지고 전반적으로 상승효과가 나타나는 점을 알 수 있다. 또한 T7 내지 T9에 의하는 경우 2 내지 4일 차에서 초기 활성이 급격히 향상되는 점을 확인할 수 있었다.On the other hand, it can be seen that the overall synergistic effect is exhibited by the mixture of E1 and E2, and in particular, in the case of T2 to T4, it can be seen that the initial improvement activity is increased and the synergistic effect is overall. In addition, in the case of T7 to T9, it was confirmed that the initial activity was rapidly improved on the 2nd to 4th day.
따라서 본 발명의 조성물에 의하는 경우 인지기능 및 기억력 개선 효과를 나타나내는데 효과가 있고 특히 초기 개선 효과가 뛰어난 기능성을 제공하게 할 수 있다. 이에 따라 인지기능 및 기억력 개선을 목적으로 하는 다양한 제품 군에 적용시켜 상용화 할 수 있다.Therefore, in the case of the composition of the present invention, it is effective in exhibiting the effect of improving cognitive function and memory, and in particular, it is possible to provide functionality excellent in the initial improvement effect. Accordingly, it can be commercialized by applying it to various product groups aimed at improving cognitive function and memory.
이상에서 본 발명의 바람직한 실시예에 대하여 상세하게 설명하였지만 본 발명의 권리범위는 이에 한정되는 것은 아니고 다음의 청구범위에서 정의하고 있는 본 발명의 기본 개념을 이용한 당업자의 여러 변형 및 개량 형태 또한 본 발명의 권리범위에 속하는 것이다.Although the preferred embodiment of the present invention has been described in detail above, the scope of the present invention is not limited thereto, and various modifications and improvements by those skilled in the art using the basic concept of the present invention as defined in the following claims are also provided. is within the scope of the
Claims (7)
기억력 및 인지기능 개선용 조성물.Containing annual extract
A composition for improving memory and cognitive function.
뉴그린 추출물을 더 포함하는
기억력 및 인지기능 개선용 조성물.According to claim 1,
which further contains New Green extract
A composition for improving memory and cognitive function.
뇌신경질환 예방 및 개선용 조성물.Containing annual extract
A composition for preventing and improving cranial nerve diseases.
뉴그린 추출물을 더 포함하는
뇌신경질환 예방 및 개선용 조성물.4. The method of claim 3,
which further contains New Green extract
A composition for preventing and improving cranial nerve diseases.
상기 뇌신경질환은 신경 퇴행성 질환, 허혈 또는 재관류에 의한 질환 및 정신 장애로 구성된 군으로부터 선택된 것이고,
상기 신경 퇴행성 질환은 파킨슨 병, 헌팅턴 병, 알츠하이머 병, 경도인지장애, 노인성 치매, 근위축성 측삭경화증(amyotrophic lateral sclerosis), 척수소뇌성 운동실조증(Spinocerebellar Atrophy), 뚜렛 증후군(Tourette`s Syndrome), 프리드리히 보행실조(Friedrich`s Ataxia), 마차도-조셉 병(Machado-Joseph`s disease), 루이 소체 치매(Lewy Body Dementia), 근육긴장이상(Dystonia), 진행성 핵상 마비(Progressive Supranuclear Palsy) 및 전두측두엽 치매(Frontotemporal Dementia)로 구성된 군으로부터 선택된 것인
뇌신경질환 예방 및 개선용 조성물.5. The method according to claim 3 or 4,
The cranial nerve disease is selected from the group consisting of neurodegenerative diseases, diseases and psychiatric disorders caused by ischemia or reperfusion,
The neurodegenerative diseases include Parkinson's disease, Huntington's disease, Alzheimer's disease, mild cognitive impairment, senile dementia, amyotrophic lateral sclerosis, Spinocerebellar Atrophy, Tourette's Syndrome, Friedrich's Ataxia, Machado-Joseph's disease, Lewy Body Dementia, Dystonia, Progressive Supranuclear Palsy and frontotemporal lobe Dementia (Frontotemporal Dementia) that is selected from the group consisting of
A composition for preventing and improving cranial nerve diseases.
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