KR20190005244A - Composition for Improving Memory, Preventing, Improving or Treating Cognitive Disorder and Brain Diseases - Google Patents
Composition for Improving Memory, Preventing, Improving or Treating Cognitive Disorder and Brain Diseases Download PDFInfo
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- KR20190005244A KR20190005244A KR1020190000948A KR20190000948A KR20190005244A KR 20190005244 A KR20190005244 A KR 20190005244A KR 1020190000948 A KR1020190000948 A KR 1020190000948A KR 20190000948 A KR20190000948 A KR 20190000948A KR 20190005244 A KR20190005244 A KR 20190005244A
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- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/44—Ebenaceae (Ebony family), e.g. persimmon
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Abstract
Description
본 발명은 기억력 개선, 인지기능장애 및 뇌질환의 예방, 개선 또는 치료용 조성물에 관한 것이다.The present invention relates to a composition for improving memory, cognitive dysfunction and prevention, improvement or treatment of brain diseases.
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.There is a sharp increase in the proportion of the elderly population globally, according to a recent analysis. By 2050, the population aged 60 or older will reach 2 billion. According to the statistics of the National Statistical Office (NSO) in 2013, 83.3% of the aged population in Korea (the ratio of elderly people aged 65 or older) is below the age of 15 and 12.2% As the elderly population increases, geriatric diseases are increasing and countermeasures are being urgently discussed. The most problematic of geriatric diseases is cognitive impairment dementia. Dementia means that the cognitive functions such as memory, language ability, time-space grasp and judgment ability, and abstract thinking ability are continuously and overall declined due to the impaired brain function, resulting in many problems in everyday life in severe cases. Alzheimer's disease and vascular dementia, as well as degenerative brain diseases such as Parkinson's disease, head trauma, and infectious diseases are known to be caused by various causes such as dementia. Therefore, the exponential increase of the elderly population is urgently needed to treat and manage the rapidly growing dementia.
고욤나무(Diospyros lotus)는 감나무과로, 중동 아시아 및 남아시아, 특히 중국 및 일본에 분포한다(Hedrick 1972). 고욤나무의 열매는 진정제, 진해제, 항균제, 항당뇨제, 항암제, 수렴제, 완화제, 영양제 및 해열제로서 전통의료로 사용되어 왔다(Simmons, 1972, Chopra et al., 1986). 또한, 고욤나무의 열매는 설사, 마른기침, 고혈압을 치료하는데 사용되었다(Bown, 1995). 이전의 연구는, 고욤나무의 열매에서, 지방산 및 비휘발성 산(Ahmet and Kadioglu, 1998), 터핀(Khasan et al., 1976), 나프토퀴논(Yoshihira et al., 1971) 및 페놀성 화합물(Rashed et al. 2012)의 피토케미칼(phytochemical)이 보고되었다.Goomae ( Diospyros lotus ) is distributed in the persimmon tree, Middle East Asia and South Asia, especially China and Japan (Hedrick 1972). The fruits of Goam's tree have been used as traditional medicines as sedatives, anti-seizures, antimicrobials, anti-diabetic agents, anticancer agents, astringents, emollients, nutrients and antipyretics (Simmons, 1972, Chopra et al., 1986). In addition, the fruits of the fruit tree were used to treat diarrhea, dry cough, and hypertension (Bown, 1995). Previous studies have shown that in the fruit of the gomam tree, fatty acids and non-volatile acids (Ahmet and Kadioglu, 1998), turpentine (Khasan et al., 1976), naphthoquinone (Yoshihira et al., 1971) Rashed et al. 2012) phytochemicals have been reported.
본 명세서 전체에 걸쳐 다수의 논문 및 특허문헌이 참조되고 그 인용이 표시되어 있다. 인용된 논문 및 특허문헌의 개시 내용은 그 전체로서 본 명세서에 참조로 삽입되어 본 발명이 속하는 기술 분야의 수준 및 본 발명의 내용이 보다 명확하게 설명된다.Numerous papers and patent documents are referenced and cited throughout this specification. The disclosures of the cited papers and patent documents are incorporated herein by reference in their entirety to better understand the state of the art to which the present invention pertains and the content of the present invention.
본 발명자들은 천연물 유래의 뇌기능 개선, 뇌질환의 예방 또는 치료용 조성물을 선별하고자 노력하였고, 그 결과, 고욤나무(Diospyros lotus L.) 추출물의 신경세포 보호 효과 및 아세틸콜린 에스터라제 활성 저해 효과 등을 확인하고 치매, 파킨슨병, 허혈성 뇌질환, 기억력 및 인지기능에 대하여 개선, 예방 또는 치료 효과가 있음을 규명함으로써 본 발명을 완성하였다.The present inventors have sought to select a composition for improving brain function and preventing or treating brain diseases derived from natural materials. As a result, it has been found that the neomycin protective effect and acetylcholinesterase activity inhibitory effect of the extract of Dioscorea lotus L. And confirmed the improvement, prevention or therapeutic effect on dementia, Parkinson's disease, ischemic brain disease, memory and cognitive function, thereby completing the present invention.
따라서, 본 발명의 목적은 기억력 개선용 식품 조성물을 제공하는 데 있다.Accordingly, an object of the present invention is to provide a food composition for improving memory performance.
본 발명의 다른 목적은 인지기능장애(cognitive disorder) 개선, 예방 또는 치료용 조성물을 제공하는 데 있다.It is another object of the present invention to provide a composition for improving, preventing or treating a cognitive disorder.
본 발명의 또 다른 목적은 뇌질환 개선, 예방 또는 치료용 조성물을 제공하는 데 있다.It is still another object of the present invention to provide a composition for improving, preventing or treating brain diseases.
본 발명의 다른 목적 및 이점은 하기의 발명의 상세한 설명, 청구범위 및 도면에 의해 보다 명확하게 된다.Other objects and advantages of the present invention will become more apparent from the following detailed description of the invention, claims and drawings.
본 발명의 일 양태에 따르면, 본 발명은 고욤나무(Diospyros lotus L.) 추출물을 유효성분으로 포함하는 기억력 개선용 식품 조성물을 제공한다.According to one aspect of the present invention, there is provided a food composition for improving memory, comprising as an active ingredient an extract of Dioscorea radix L. ( Diospyros lotus L. ).
본 발명의 다른 양태에 따르면, 본 발명은 고욤나무 추출물을 유효성분으로 포함하는 인기지능장애(cognitive disorder) 개선, 예방 또는 치료용 조성물을 제공한다.According to another aspect of the present invention, there is provided a composition for improving, preventing or treating a cognitive disorder, which comprises an extract of Gomam tree as an active ingredient.
본 발명의 또 다른 양태에 따르면, 본 발명은 고욤나무 추출물을 유효성분으로 포함하는 뇌질환 개선, 예방 또는 치료용 조성물을 제공한다.According to still another aspect of the present invention, there is provided a composition for improving, preventing or treating brain diseases comprising an extract of Gomam tree as an active ingredient.
본 발명자들은 천연물 유래의 뇌기능 개선, 뇌질환의 예방 또는 치료용 조성물을 선별하고자 노력하였고, 그 결과, 고욤나무(Diospyros lotus L.) 추출물의 신경세포 보호 효과 및 아세틸콜린 에스터라제 활성 저해 효과 등을 확인하고 치매, 파킨슨병, 허혈성 뇌질환, 기억력 및 인지기능에 대하여 개선, 예방 또는 치료 효과가 있음을 규명하였다.The present inventors have sought to select a composition for improving brain function and preventing or treating brain diseases derived from natural materials. As a result, it has been found that the neomycin protective effect and acetylcholinesterase activity inhibitory effect of the extract of Dioscorea lotus L. And confirmed the improvement, prevention, or therapeutic effect on dementia, Parkinson's disease, ischemic brain disease, memory and cognitive function.
본 발명의 조성물에서 이용되는 고욤나무 추출물은 고욤나무에 추출용매를 처리하여 수득하는 경우에는, 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(dimethyl-formamide) 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.When extracting the gomam tree used in the composition of the present invention, various extracting solvents may be used when the gomam tree is obtained by treating the extractant. Preferably, a polar solvent or a non-polar solvent can be used. Suitable polar solvents are (i) water, (ii) alcohols (preferably methanol, ethanol, propanol, butanol, n-propanol, iso-propanol, n-butanol, 1-pentanol, Or ethylene glycol), (iii) acetic acid, (iv) dimethyl-formamide (DMFO) and (v) dimethyl sulfoxide (DMSO). Suitable nonpolar solvents are acetone, acetonitrile, ethyl acetate, methyl acetate, fluoroalkane, pentane, hexane, 2,2,4-trimethylpentane, decane, cyclohexane, cyclopentane, diisobutylene, 1- But are not limited to, pentane, 1-chlorobutane, 1-chloropentane, o -xylene, diisopropyl ether, 2- chloropropane, toluene, 1- chloropropane, chlorobenzene, benzene, diethyl ether, diethylsulfide, Methane, 1,2-dichloroethane, aniline, diethylamine, ether, carbon tetrachloride, 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. 가장 바람직하게는, 본 발명의 추출물은 물, 에탄올 또는 이의 조합을 고욤나무에 처리하여 수득한 것이다.More preferably, the extraction solvent used in the present invention is (a) water, (b) anhydrous or hydrated lower alcohol having 1 to 4 carbon atoms (methanol, ethanol, propanol, butanol, etc.) (E) ethyl acetate, (f) chloroform, (g) butyl acetate, (h) 1,3-butylene glycol, (i) hexane and (j) diethyl ether. . Most preferably, the extract of the present invention is obtained by treating water, ethanol or a combination thereof with cyamine.
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, 고욤나무 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, 초임계 유체를 이용한 추출 등, 추가적으로 실시된 다양한 정제 방법을 통해 얻어진 분획도 본 발명의 고욤나무 추출물에 포함되는 것이다.As used herein, the term " extract " means that it is used in the art as a crude extract as described above, but broadly includes fractions obtained by further fractionating the extract. That is, the Gomam tree extract is obtained not only by using the above-mentioned extraction solvent but also by additionally applying a purification process thereto. For example, the extract can be separated into fractions obtained by passing the extract through an ultrafiltration membrane having a constant molecular weight cut-off value, separation by various chromatography (manufactured for separation according to size, charge, hydrophobicity or affinity) The fraction obtained through various purification methods, such as extraction, is also included in the Gomam tree extract of the present invention.
본 발명에서 이용되는 고욤나무 추출물은 감압 증류 및 동결 건조 또는 분무 건조 등과 같은 추가적인 과정에 의해 분말 상태로 제조될 수 있다.The gomam extract used in the present invention can be prepared in powder form by an additional process such as vacuum distillation and freeze drying or spray drying.
바람직한 구현예에 따르면, 본 발명에서 이용되는 고욤나무 추출물은 감압 농축하여 사용하였다.According to a preferred embodiment, the Koomomoe extract used in the present invention is used by concentration under reduced pressure.
본 명세서에서 용어 ‘유효성분으로 포함하는’이란 하기의 고욤나무 추출물 의 효능 또는 활성을 달성하는 데 충분한 양을 포함하는 것을 의미한다. 본 발명은 천연식물재료인 고욤나무로부터 추출한 조성물로서 과량 투여하여도 인체에 부작용이 없으므로 고욤나무 추출물이 본 발명의 조성물에 포함된 양적 상한은 당업자가 적절한 범위 내에서 선택하여 실시할 수 있다.As used herein, the term " comprising as an active ingredient " is meant to include an amount sufficient to achieve the efficacy or activity of the chewing gum extract described below. Since the composition of the present invention is extracted from a natural plant material, it is not adversely affecting the human body even when administered in an excessive amount. The quantitative upper limit of the composition of the present invention can be selected by a person skilled in the art within a suitable range.
본 발명의 상기 고욤나무 추출물은 고욤나무의 어떠한 부분을 이용할 수 있으며, 예컨대, 열매, 줄기, 잎 및 뿌리를 이용할 수 있으며, 본 발명의 일 구현예에 따르면, 상기 고욤나무 추출물은 고욤나무 잎 추출물이다.According to one embodiment of the present invention, the Gomam tree extract may be selected from the group consisting of Gomam tree leaf extract, to be.
본 발명의 고욤나무 추출물을 유효성분으로 포함하는 조성물은 기억력 개선 효과를 갖는다.The composition comprising the extract of Gomam tree of the present invention as an active ingredient has an effect of improving memory.
본 발명의 일 구현예에 따르면, 상기 고욤나무 추출물은 기억력 지속 시간을 3-10배 증가시킨다. 본 발명의 다른 구현예에 따르면, 상기 기억력 지속 시간을 3-7배 또는 3-5배 증가시킨다.According to one embodiment of the present invention, the Gomam tree extract increases the memory duration by 3-10 times. According to another embodiment of the present invention, the memory duration is increased 3-7 times or 3-5 times.
본 발명의 다른 구현예에 따르면, 상기 고욤나무 추출물은 기억력 감퇴를 억제하는 효과를 갖는다.According to another embodiment of the present invention, the Gomam tree extract has an effect of suppressing memory decline.
이러한 고욤나무 추출물의 기억력 개선 효과는 기억력 감퇴 대상(subjects) 뿐 아니라, 정상 대상에서도 동일한 효과를 나타낸다.The effect of improving the memory of Gomam tree extract is the same as that of normal subjects, as well as subjects suffering from memory loss.
본 발명의 고욤나무 추출물을 유효성분으로 포함하는 조성물은 신경세포 보호 효과를 갖는다.The composition comprising the extract according to the present invention as an active ingredient has a nerve cell protective effect.
*본 발명의 일 구현예에 따르면, 치매의 원인물질로 알려진 베타아밀로이드 단백질에 대하여 신경세포 보호 효과를 갖는다. 상세하게는, 상기 베타아밀로이드 단백질에 의한 신경독성에 대하여 고욤나무 추출물은 신경세포의 생존율을 증가시키는 효과를 갖는다. 본 발명의 다른 구현예에 따르면, 상기 신경세포의 생존율은 1.2-2.0, 1.4-1.8 또는 1.5-1.7 증가된다.According to one embodiment of the present invention, the neuroprotective effect against beta amyloid protein known as a causative substance of dementia is obtained. Specifically, the neomycin toxin caused by the beta amyloid protein has an effect of increasing the survival rate of neuronal cells. According to another embodiment of the present invention, the survival rate of the neuron is increased by 1.2-2.0, 1.4-1.8 or 1.5-1.7.
본 명세서에서 “신경 세포”는 중추 신경계, 뇌, 뇌간, 척수, 중추 신경계와 말초 신경계의 접합부분 등의 구조를 이루는 뉴런, 신경지지 세포, 글리아, 슈만 세포 등을 포함한다.As used herein, the term " nerve cell " includes neurons, nerve-supporting cells, glia, and Schumann cells constituting structures such as the central nervous system, brain, brainstem, spinal cord, and junctions of the central nervous system and peripheral nervous system.
본 발명의 고욤나무 추출물을 유효성분으로 포함하는 조성물은 아세틸콜린 활성 저해 효과를 갖는다.The composition comprising the extract of the present invention as an active ingredient has an acetylcholine activity inhibitory effect.
본 발명의 일 구현예에 따르면, 상기 고욤나무 추출물은 아세틸콜린의 활성을 20-50% 저해한다. 본 발명의 다른 구현예에 따르면, 상기 아세틸콜린의 활성을 20-40% 저해한다.According to one embodiment of the present invention, the gomam tree extract inhibits acetylcholine activity by 20-50%. According to another embodiment of the present invention, the activity of the acetylcholine is inhibited by 20-40%.
본 발명의 고욤나무 추출물을 유효성분으로 포함하는 조성물은 파킨슨병 완화 효과를 갖는다. 상세하게는, 파킨슨병 완화 효과를 확인하기 위해 파킨슨병 동물모델에서 도파민성 신경세포의 사멸되어 선조체 내 도파민의 농도가 감소되면 선조체 내 도파민 수용체의 과민성이 유발되어 아포몰핀이 도파민 수용체의 효현제로 작용하여 과민성이 유발된 선조체를 과도하게 흥분시킴으로서 동물의 손상측과 반대방향으로 회전운동하는 원리를 이용한다.The composition comprising the extract of the present invention as an active ingredient has a Parkinson's disease mitigating effect. Specifically, in order to confirm the mitigation effect of Parkinson's disease, when the dopamine neuronal cell death in the Parkinson's disease model is reduced and the concentration of dopamine in the striatum is decreased, the hypersensitivity of the dopamine receptor in the striatum is induced and apomorphine acts as an agonist of the dopamine receptor By overexciting the irritable striatum, we use the principle of rotating in the opposite direction to the damaged side of the animal.
본 발명의 일 구현예에 따르면, 상기 고욤나무 추출물은 파킨슨병 모델의 병변 대조군과 비교하여 일측성 순 회전수를 50-90% 감소시킨다. 본 발명의 다른 구현예에 따르면, 상기 고욤나무 추출물은 일측성 순 회전수를 55-85% 또는 60-80% 감소시킨다.According to one embodiment of the present invention, the Gomam tree extract reduces the unilateral net rotation rate by 50-90% as compared to the lesion control of the Parkinson's disease model. According to another embodiment of the present invention, the Gomam tree extract reduces the unilateral net rotation number by 55-85% or 60-80%.
본 발명의 고욤나무 추출물을 유효성분으로 포함하는 조성물은 뇌질환 예방 또는 치료 효과를 갖는다.The composition comprising the extract of the present invention as an active ingredient has an effect of preventing or treating brain diseases.
본 발명의 일 구현예에 따르면, 허혈성 뇌질환의 뇌기능 손상에 의한 행동변화를 완화하는 효과를 갖는다.According to one embodiment of the present invention, it is possible to mitigate behavioral changes caused by damage to brain function of ischemic brain diseases.
본 발명의 다른 구현예에 따르면, 허혈성 뇌질환의 뇌기능 손상에 의한 신경손상을 완화하는 효과를 갖는다.According to another embodiment of the present invention, there is an effect of alleviating nerve damage due to damage of brain function of ischemic brain disease.
본 명세서에서 “인지기능장애”는 기억처리, 지각 및 문제해결과 같은 인지기능을 발휘하지 못하는 질환을 의미한다.As used herein, the term " cognitive dysfunction " means a disease that does not exhibit cognitive functions such as memory processing, perception, and problem solving.
본 발명의 일 구현예에 따르면, 상기 인지기능장애는 치매, 학습장애, 실인증, 건망증, 실어증, 실행증, 섬망, AIDS 유발 치매, 빈스완거 병, 루이소체 치매, 전두측두엽성 치매, 경도 인지 장애, 다발성 경색성 치매, 픽병, 의미치매, 알츠하이머성 치매 또는 혈관성 치매로 구성된 군으로부터 선택되는 인지기능 장애이다.According to one embodiment of the present invention, the cognitive dysfunction is selected from the group consisting of dementia, learning disorder, actual authentication, forgetfulness, aphasia, performance test, delirium, AIDS induced dementia, Vince dementia, , Multiple infarct dementia, Pick's disease, semantic dementia, Alzheimer's dementia or vascular dementia.
본 명세서에서 “뇌질환”은 뇌혈관 또는 뇌신경의 손상에 의해 뇌조직의 기능이 가역적 또는 비가역적으로 저하 또는 소실되는 병적상태(pathologic condition)를 의미한다.As used herein, the term " brain disease " refers to a pathologic condition in which the function of brain tissue is reversibly or irreversibly reduced or lost by damage of cerebral blood vessels or brain nerves.
본 발명의 일 구현예에 따르면, 상기 뇌질환은 뇌혈관 질환, 외상성 뇌손상 및 신경퇴행성 질환으로 구성된 군으로부터 선택되는 뇌질환이다.According to one embodiment of the present invention, the brain disease is a brain disease selected from the group consisting of cerebrovascular disease, traumatic brain injury and neurodegenerative diseases.
본 발명의 다른 구현예에 따르면, 상기 뇌혈관 질환은 허혈성 또는 출혈성 뇌졸중, 저산소성-허혈성 뇌손상, 저산소성 뇌손상 및 뇌성마비로 구성된 군으로부터 선택되는 뇌혈관 질환이다.According to another embodiment of the present invention, the cerebrovascular disease is a cerebrovascular disease selected from the group consisting of ischemic or hemorrhagic stroke, hypoxic-ischemic brain injury, hypoxic brain injury and cerebral palsy.
본 명세서에서 “허혈성 또는 출혈성 뇌졸중”은 심장에 혈액을 공급하는 관상동맥이 협소해지거나 폐색되어 심장근육으로의 혈류가 감소함으로서 초래되는 질환을 의미한다.As used herein, " ischemic or hemorrhagic stroke " refers to a disease caused by the narrowing or occlusion of the coronary arteries supplying blood to the heart, resulting in reduced blood flow to the heart muscle.
본 명세서에서 “신경퇴행성 질환”은 신경 세포의 구조 및 기능의 점진적 손실(progressive loss)에 의한 질환을 의미한다.As used herein, the term " neurodegenerative disease " refers to a disease caused by progressive loss of the structure and function of nerve cells.
본 발명의 일 구현예에 따르면, 상기 신경퇴행성 질환은 파킨슨병(Parkinson’s disease), 알쯔하이머병(Alzheimer's disease), 뇌졸중(stroke), 근위축성측색경화증(amyotrophic lateral sclerosis), 빈스완거병(Binswanger’s disease), 헌팅톤 무도병(Huntington’s chorea), 다발성 경화증(multiple sclerosis), 중증근무력증(myasthenia gravis) 또는 피크병(Pick’s disease)으로 구성된 군으로부터 선택되는 신경퇴행성 질환이다.According to an embodiment of the present invention, the neurodegenerative diseases are Parkinson's disease, Alzheimer's disease, stroke, amyotrophic lateral sclerosis, Binswanger's disease, Huntington ' s chorea, multiple sclerosis, myasthenia gravis or Pick's disease. ≪ Desc /
본 명세서에서 “파킨슨병”은 파킨슨병(Parkinson's disease)은 중추신경계의 진행형 퇴행성 질환으로, 중뇌(midbrain)의 한 부위인 흑질(substantia nigra)에 존재하는 도파민-발생 세포(예컨대, 도파민 뉴런)의 세포사멸로부터 야기된다. 상기 질환의 증상으로, 초기에는 운동과 관련된 증상(예컨대, 느린 운동, 정지시 떨림, 근육 강직, 질질 끌며 걷기, 굽은 자세 등)을 명확하게 나타내며, 진행됨에 따라 인식(cognitive) 및 행동 장애를 일으키고, 가장 진전된 단계에서는 공통적으로 치매(dementia) 증상을 나타낸다. 다른 증상으로는, 감각 장애, 수면 장애 및 감정 장애를 포함한다. 파킨슨병은 50세 이후에 발생되는 가장 보편적인 질환으로, 나이가 들어감에 따라 발병하는 가장 일반적인 질환이다.As used herein, " Parkinson's disease " refers to Parkinson ' s disease, a progressive, degenerative disease of the central nervous system that is associated with dopaminergic neurons (e.g., dopaminergic neurons) present in the substantia nigra, Resulting from apoptosis. Symptoms of the disease include, but are not limited to, early manifestations of exercise-related symptoms (e.g., slow motion, tremor at rest, muscle rigidity, gait walking, flexion posture, etc.), progressive cognitive and behavioral disorders , And dementia symptoms commonly present at the most advanced stages. Other symptoms include sensory disorders, sleep disorders, and affective disorders. Parkinson's disease is the most common disease occurring after
본 발명의 고욤나무 추출물을 유효성분으로 포함하는 조성물은 식품 조성물, 기능성 식품 조성물 또는 약제학적 조성물이다.The composition comprising the extract of Gomam tree as an active ingredient of the present invention is a food composition, a functional food composition or a pharmaceutical composition.
본 발명의 조성물은 식품 조성물로 제공될 수 있다. 본 발명의 고욤나무 추출물을 유효성분 포함하는 조성물이 식품 조성물로 제조되는 경우, 유효성분으로서 고욤나무 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, 수크로스, 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. 예컨대, 본 발명의 식품 조성물이 드링크제로 제조되는 경우에는 본 발명의 고욤나무 추출물 이외에 구연산, 액상과당, 설탕, 포도당, 초산, 사과산, 과즙, 두충 추출액, 대추 추출액, 감초 추출액 등을 추가로 포함시킬 수 있다.The composition of the present invention can be provided as a food composition. When the composition comprising the active ingredient of the extract of the present invention is prepared from a food composition, it contains not only an extract of Gomam tree as an active ingredient but also a component which is ordinarily added at the time of food production, for example, a protein, a carbohydrate , Fats, nutrients, flavoring agents, and flavoring agents. Examples of the above-mentioned carbohydrates are monosaccharides such as glucose, fructose, and the like; Disaccharides such as maltose, sucrose, oligosaccharides and the like; And polysaccharides such as dextrin, cyclodextrin and the like, and sugar alcohols such as xylitol, sorbitol and erythritol. Natural flavorings such as tau martin and stevia extract (e.g., rebaudioside A and glycyrrhizin) and synthetic flavorings (saccharine, aspartame, etc.) can be used as flavorings. For example, when the food composition of the present invention is prepared as a drink, it may further include citric acid, liquid fructose, sugar, glucose, acetic acid, malic acid, juice, mulberry extract, jujube extract, licorice extract, .
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, 탄산음료에 사용되는 탄산화제 등을 함유할 수 있다. 그밖에 본 발명의 조성물들은 천연 과일 주스 및 과일 주스 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-mentioned composition, the composition of the present invention can be used as a flavoring agent such as various nutrients, vitamins, minerals (electrolytes), synthetic flavors and natural flavors, coloring agents and intermediates (cheese, chocolate etc.), pectic acid and its salts, Salts, organic acids, protective colloid thickening agents, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, carbonating agents used in carbonated beverages and the like. In addition, the compositions of the present invention may contain flesh for the production of natural fruit juices and fruit juice drinks and vegetable drinks. These components may be used independently or in combination. The proportion of such additives is not so critical, but is generally selected in the range of 0 to about 20 parts by weight per 100 parts by weight of the composition of the present invention.
본 발명의 조성물 중 고욤나무 추출물을 포함하는 조성물의 바람직한 함유량으로는 식품의 전체 중량에 대하여 약 0.1-50.0 중량%를 포함할 수 있다. 바람직하게는 0.5-10 ㎎/㎏/day의 양으로 섭취하는 경우 두뇌 또는 인지기능 증진 및 뇌질환 예방 효과가 나타날 수 있다. The preferred content of the composition comprising the chelomotin extract in the composition of the present invention may include about 0.1-50.0 wt% based on the total weight of the food. Preferably 0.5-10 mg / kg / day, may be effective for brain or cognitive function enhancement and brain disease prevention.
본 발명의 고욤나무 추출물을 유효성분으로 포함하는 조성물은 기능성 식품 조성물로 제조될 수 있다. 본 발명의 조성물이 기능성 식품 조성물로 제조되는 경우, 식품 제조 시 통상적으로 첨가되는 성분을 포함하며, 예를 들어, 단백질, 탄수화물, 지방, 영양소 및 조미제를 포함한다. 예컨대, 드링크제로 제조되는 경우에는 유효성분으로서 고욤나무 추출물 이외에 향미제 또는 천연 탄수화물을 추가 성분으로 포함시킬 수 있다. 예를 들어, 천연 탄수화물은 모노사카라이드(예컨대, 글루코오스, 프럭토오스 등); 디사카라이드(예컨대, 말토스, 수크로오스 등); 올리고당; 폴리사카라이드(예컨대, 덱스트린, 시클로덱스트린 등); 및 당알코올(예컨대, 자일리톨, 소르비톨, 에리쓰리톨 등)을 포함한다. 향미제로서 천연 향미제(예컨대, 타우마린, 스테비아 추출물 등) 및 합성 향미제(예컨대, 사카린, 아스파르탐 등)을 이용할 수 있다.The composition comprising the extract of Gomam tree of the present invention as an active ingredient may be prepared from a functional food composition. When the composition of the present invention is prepared with a functional food composition, it includes components that are conventionally added in food production, and includes, for example, proteins, carbohydrates, fats, nutrients, and seasonings. For example, in the case of being made with a drink, as an active ingredient, a flavoring agent or a natural carbohydrate may be included as an additional ingredient in addition to the gomame tree extract. For example, natural carbohydrates include monosaccharides (e.g., glucose, fructose, etc.); Disaccharides (e.g., maltose, sucrose, etc.); oligosaccharide; Polysaccharides (e.g., dextrin, cyclodextrin and the like); And sugar alcohols (e.g., xylitol, sorbitol, erythritol, etc.). Natural flavoring agents (e.g., tau marin, stevia extract, etc.) and synthetic flavoring agents (e.g., saccharin, aspartame, etc.) may be used as flavorings.
본 발명의 조성물은 약제학적 조성물로 제조될 수 있다. The compositions of the present invention may be prepared with pharmaceutical compositions.
본 발명의 바람직한 구현예에 따르면, 본 발명의 조성물은 (a) 상술한 본 발명의 고욤나무 추출물의 약제학적 유효량; 및 (b) 약제학적으로 허용되는 담체를 포함하는 약제학적 조성물이다. 본 명세서에서 용어 “약제학적 유효량”은 상술한 고욤나무 추출물의 효능 또는 활성을 달성하는 데 충분한 양을 의미한다.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 chewoma extract of the present invention; And (b) a pharmaceutically acceptable carrier. As used herein, the term " pharmaceutically effective amount " means an amount sufficient to achieve the efficacy or activity of the above-mentioned Goat's wood extract.
본 발명의 조성물이 약제학적 조성물로 제조되는 경우, 본 발명의 약제학적 조성물은 약제학적으로 허용되는 담체를 포함한다. 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. 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.When the composition of the present invention is manufactured from a pharmaceutical composition, the pharmaceutical composition of the present invention includes a pharmaceutically acceptable carrier. The pharmaceutically acceptable carriers to be contained in the pharmaceutical composition of the present invention are those conventionally used in the present invention and include lactose, dextrose, sucrose, sorbitol, mannitol, starch, acacia rubber, calcium phosphate, alginate, gelatin, But are not limited to, calcium silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, water, syrups, methylcellulose, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil. It is not. The pharmaceutical composition of the present invention may further contain a lubricant, a wetting agent, a sweetening agent, a flavoring agent, an emulsifying agent, a suspending agent, a preservative, etc. in addition to the above components. Suitable pharmaceutically acceptable carriers and formulations are described in detail in Remington ' s Pharmaceutical Sciences (19th ed., 1995).
본 발명의 약제학적 조성물은 경구 또는 비경구 투여할 수 있으며, 바람직하게는 경구 투여 방식으로 적용된다.The pharmaceutical composition of the present invention can be administered orally or parenterally, and is preferably administered orally.
본 발명의 약제학적 조성물의 적합한 투여량은 제제화 방법, 투여 방식, 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 약제학적 조성물의 일반적인 투여량은 성인 기준으로 0.001-100 ㎎/kg 범위 내이다.The appropriate dosage of the pharmaceutical composition of the present invention may vary depending on factors such as the formulation method, administration method, age, body weight, sex, pathological condition, food, administration time, administration route, excretion rate, . Typical dosages of the pharmaceutical compositions of this invention are in the range of 0.001-100 mg / kg on an adult basis.
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 수성 매질중의 용액, 현탁액, 시럽제 또는 유화액 형태이거나 엑스제, 산제, 분말제, 과립제, 정제 또는 캅셀제 형태일 수도 있으며, 분산제 또는 안정화제를 추가적으로 포함할 수 있다.The pharmaceutical composition of the present invention may be formulated into a unit dose form by formulating it using a pharmaceutically acceptable carrier and / or excipient according to a method which can be easily carried out by a person having ordinary skill in the art to which the present invention belongs. Or by intrusion into a multi-dose container. The formulations may be in the form of solutions, suspensions, syrups or emulsions in oils or aqueous media, or in the form of excipients, powders, powders, granules, tablets or capsules, and may additionally contain dispersing or stabilizing agents.
본 발명의 특징 및 이점을 요약하면 다음과 같다:The features and advantages of the present invention are summarized as follows:
(a) 본 발명은 고욤나무 추출물을 유효성분으로 포함하는 기억력 개선용, 인지기능장애(cognitive disorder) 개선, 예방 또는 치료용 조성물 및 뇌질환 개선, 예방 또는 치료용 조성물을 제공한다.(a) The present invention provides a composition for improving memory, a cognitive disorder, a composition for preventing or treating cognitive impairment, and a composition for improving, preventing or treating brain diseases, which comprises as an active ingredient an extract of cedarwood.
*(b) 본 발명의 고욤나무 추출물은 기억력 개선 및 감퇴 억제, 인지기능 장애 개선, 예방 또는 치료, 및 뇌질환 개선, 예방 또는 치료 효과를 갖는다.(b) The extract of Guoxam extract of the present invention has the effects of improving memory and suppressing decline, improving cognitive dysfunction, preventing or treating, and improving or preventing or treating brain diseases.
로이드 단백질(Aβ)을 첨가한 후, 세포 생존율을 측정한 결과를 나타낸다.
도 2는 치매 동물모델에 대한 고욤나무 추출물의 치매 개선 효과를 나타낸다.
도 3은 고욤나무 추출물이 우수한 아세틸콜린 에스터라제 저해 효과를 나타낸다.
도 4는 파킨슨병 동물모델에 대한 고욤나무 추출물의 파킨슨병 개선 효과를 나타낸다.
도 5는 허혈성 뇌질환 동물모델에 대한 고욤나무 추출물의 로타로드(rotarod) 행동시험 결과를 나타낸다.
도 6은 허혈성 뇌질환 동물모델에 대한 고욤나무 추출물의 신경손상 억제 효과를 나타낸다.
도 7은 고욤나무 추출물의 기억력 감퇴 예방 효과를 나타낸다.
도 8은 정상 동물에서 고욤나무 추출물의 기억력 및 인지기능 개선 효과를 나타낸다.Lloid protein (A [beta]) was added and the cell viability was measured.
Figure 2 shows the dementia improvement effect of Gomam extract on dementia animal models.
FIG. 3 shows the acetylcholinesterase inhibitory effect of Gomam extract.
4 shows the Parkinson's disease-improving effect of the Koomomoe extract on the Parkinson's disease animal model.
Figure 5 shows the rotarod behavioral test results of Koomomoe extracts on ischemic brain disease animal models.
Figure 6 shows the neuroprotective effect of Guillain-Root Extract on the ischemic brain disease animal model.
FIG. 7 shows the effect of preventing the decline of the memory of Guillaume Extract.
8 shows the memory and cognitive function improving effect of the Guillaume extract on normal animals.
이하, 실시예를 통하여 본 발명을 더욱 상세히 설명하고자 한다. 이들 실시예는 오로지 본 발명을 보다 구체적으로 설명하기 위한 것으로, 본 발명의 요지에 따라 본 발명의 범위가 이들 실시예에 의해 제한되지 않는다는 것은 당업계에서 통상의 지식을 가진 자에 있어서 자명할 것이다.Hereinafter, the present invention will be described in more detail with reference to Examples. It is to be understood by those skilled in the art that these embodiments are only for describing the present invention in more detail and that the scope of the present invention is not limited by these embodiments in accordance with the gist of the present invention .
실시예Example
실시예Example 1: 고욤나무( 1: Goomae ( DiospyrosDiospyros lotus L. lotus L. ) 추출물의 제조) Preparation of extract
고욤나무(Diospyros lotus L.) 잎을 선별하여 분쇄한 뒤, 분쇄물 중량의 10배(w/v) 정제수를 용매로 하여 2시간 이상 열수추출하고, 5배의 정제수를 가하여 2차 추출하여 추출물을 여과포로 여과하였다. 여액을 감압 농축한 후, 추출물과 덱스트린을 1:1로 혼합하여 분무건조하여 분말 추출물을 획득하였다.The leaf of Dioscoros lotus L. was screened and pulverized. The extract was subjected to hot water extraction for 2 hours or more with purified water of 10 times (w / v) of the weight of the pulverized material, followed by secondary extraction with 5 times of purified water, Was filtered with a filter cloth. The filtrate was concentrated under reduced pressure, and the extract and dextrin were mixed at a ratio of 1: 1 and spray-dried to obtain a powdery extract.
실시예Example 2: 치매 예방 효과 2: Prevention of dementia
세포배양Cell culture
인간 신경모세포종(neuroblastoma cell)인 SK-N-SH 세포는 DMEM에 10% FBS (fetal bovine serum)를 보충한 배양액으로 배양하였다. 실험하기 2시간 전에 low serum media(DMEM with 1% FBS)로 바꾸어주었다.SK-N-SH cells, which are human neuroblastoma cells, were cultured in DMEM supplemented with 10% FBS (fetal bovine serum). Two hours before the experiment, low serum media (DMEM with 1% FBS) was used.
베타 아밀로이드 단백질(Beta amyloid protein ( AβAβ 1One -42-42 ))
베타 아밀로이드 단백질(Aβ1 - 42)은 Biosource(California, USA)에서 구입하였고, 0.1 M 인산염완충식염수(PBS, pH 7.4)로 용해시켜 사용하였다. Aβ1 -42를 사용하기 전에 37℃에서 2시간 배양하여 에이징(aging) 단계를 거쳤다. Aβ1 -42는 10 μ로 사용하였고, 이 농도는 36시간에 55% 정도의 세포 생존율을 보였다.Beta amyloid protein (Aβ 1 - 42 ) was purchased from Biosource (California, USA) and dissolved in 0.1 M phosphate buffered saline (PBS, pH 7.4). The A [beta] i- 42 was incubated at 37 [deg.] C for 2 hours before use and subjected to an aging step. Aβ 1 -42 was used as 10 μM, and this concentration showed cell viability of about 55% at 36 hours.
세포생존율 측정(Cell viability measurement ( AlamarblueAlamarblue assay) assay)
SK-N-SH 세포는 각각 96-well 마이크로플레이트(Nunc, Slangerup, Denmark)에 15,000 cells/well의 밀도로 24시간 동안 배양하였다. 세포 배양액을 1% FBS가 들어있는 DMEM으로 갈아주고 2시간 동안 추가로 배양하였다. 배양된 세포에 고욤나무 추출물을 10 μ농도가 되도록 첨가하고 음성대조군으로는 0.1 M PBS(pH 7.4)를 동일한 양 첨가하여 2시간을 추가로 배양하였다. 이후 각 군의 배양액에 Aβ1-42를 20 μ이 되도록 첨가하고 2시간을 추가로 배양하였다. Aβ1 -42 처리에 대한 음성대조군으로는 0.1 M PBS(pH 7.4)를 동일한 양 첨가하여 배양하였다.SK-N-SH cells were cultured in 96-well microplates (Nunc, Slangerup, Denmark) for 24 hours at a density of 15,000 cells / well. The cell culture medium was changed to DMEM containing 1% FBS and further cultured for 2 hours. To the cultured cells, Koomomoe extract was added to a concentration of 10 μM, and the same amount of 0.1 M PBS (pH 7.4) was added as a negative control for 2 hours. Then, Aβ 1-42 was added to the culture solution of each group so as to have a concentration of 20 μM , and further incubated for 2 hours. As negative control for A [beta] i- 42 treatment, the same amount of 0.1 M PBS (pH 7.4) was added and cultured.
이후 알라마블루(alamarblue, Serotec, Oxford, UK)를 10 ㎕ 처리한 후 3시간 배양하고, ELISA 리더기(Molecular Divices, Sunnycale, CA, USA)를 이용하여 570 ㎚에서 흡광도를 측정하였다. 블랭크 흡광도(blank count)는 600 ㎚에서 측정한 값을 사용하였다.Then, 10 μl of alamarblue (Serotec, Oxford, UK) was treated and incubated for 3 hours. Absorbance was measured at 570 nm using an ELISA reader (Molecular Divices, Sunnycale, CA, USA). Blank absorbance (blank count) was measured at 600 nm.
고욤나무 추출물의 신경세포 보호 효과를 확인하기 위하여, 신경모세포종에 베타 아밀로이드 단백질(Aβ)을 첨가하였다. 세포 생존율을 측정한 결과, 도 1에서 확인할수 있듯이 베타 아밀로이드 단백질을 처리하지 아니한 경우 세포의 생존율에 차이가 나타나지 아니하나 베타 아밀로이드 단백질을 처리한 경우 세포의 생존율이 떨어지는 것을 확인하였다. 그러나 고욤나무 추출물을 처리한 실험군의 경우, 베타 아밀로이드 단백질에 의한 신경독성에도 불구하고 신경세포의 생존율이 거의 약 81% 정도로 유지되는 것을 확인하였다.In order to confirm neuronal protection effect of Gomam tree extract, beta amyloid protein (Aβ) was added to neuroblastoma. As shown in FIG. 1, the cell survival rate was not different when the beta amyloid protein was not treated, but the cell survival rate was decreased when beta amyloid protein was treated. However, the survival rate of neomatous cells was maintained at about 81% in the experimental group treated with cheomom tree extract, despite neurotoxicity caused by beta amyloid protein.
치매 모델 제작Dementia model making
평균 무게 25 g의 웅성 ICR 마우스에 실험동물을 케타민(Ketamine, 40 ㎎/㎏) 및 자일라진(Xylazine, 20 ㎎/㎏)을 이용하여 마취를 한 뒤, 마취동물을 뇌정위수술기구(stereotaxic frame, David Kopf, USA)를 이용하여 두개골을 천공하고, 치매를 유도할 수 있는 Aβ1 -42를 가쪽뇌실(lateral ventricle)에 주입하여 치매 모델을 제작하였다. 상기 <실시예 1>에서 제조한 고욤나무 추출물을 생리식염수에 희석하여 Aβ1 -42 투여 3일 전부터 50 ㎎/㎏ 용량으로 20일 동안 매일 1회 복강주사로 투여하였다.Animals were anesthetized with ketamine (40 ㎎ / ㎏) and xylazine (20 ㎎ / ㎏) in male ICR mice with an average weight of 25 g and anesthetized animals were treated with stereotaxic frame , David Kopf, USA), and a dementia model was constructed by injecting Aβ 1 -42 , which can induce dementia, into the lateral ventricle. The gomam extract prepared in Example 1 was diluted in physiological saline and administered intraperitoneally once daily for 20 days at a dose of 50 mg / kg from 3 days before the administration of A? 1 -42 .
수동회피능력시험Passive avoidance ability test
상기 <실시예 1> 에서 얻은 고욤나무 추출물이 Aβ1 -42 투여로 유도된 치매 모델에서 실험쥐의 인지능력에 미치는 영향을 평가하기 위해, 상기 치매 모델 마우스를 상대로 수동회피능력시험을 시행하였다.In order to evaluate the effect of the Gomam tree extract obtained in Example 1 on the cognitive ability of the experimental rat in the dementia model induced by administration of A? 1 -42 , the manual avoidance ability test was performed on the demented model mouse.
수동회피 실험 기구는 2개의 구역으로 나뉘어져 있는데 가운데 문을 통하여 서로 이동할 수 있도록 되어 있으며, 바닥은 철망으로 이루어져 실험동물이 어두운 곳에서 90초 동안의 적응기간을 두고 난 뒤에 빛과 소음의 요소가 작용하면 열린 문을 통하여 다른 어두운 구역으로 이동하여 빛과 소음을 피할 수 있게 구성하였다. 훈련 시 빛과 소음의 자극을 주어서 어두운 구역으로 이동하면, 1.5 ㎃의 전류가 2초간 흐르는 발 쇼크(foot shock)을 받게 하였다. 훈련을 받은 지 24시간 경과 후, 쥐를 처음 구역에 넣고 90초 동안의 적응기간이 지나고 난 뒤 빛과 소음의 자극을 주어서 어두운 구역으로 이동하는데 걸리는 시간을 측정하였다. 측정 최대 시간은 300초로 하였다(Sonkusare et al., Life Sci . 77(1). 1-14. 2005).The passive avoidance test apparatus is divided into two sections, which are movable through the middle door. The floor is made of wire mesh. After the adaptation period of 90 seconds in the dark place, the light and noise elements I made it possible to move to another dark area through the open door to avoid light and noise. During training, light and noise were stimulated and moved to a dark area, causing a current of 1.5 mA to undergo a two - second foot shock. Twenty-four hours after the training, the mice were placed in the first zone and the time taken to move to the dark zone after stimulation with light and noise was measured after 90 seconds of adaptation. The maximum time of measurement was 300 seconds (Sonkusare et al., Life Sci . 77 (1), 1-14, 2005).
실험 결과, 도 2에서 보는 바와 같이 치매를 유도한 마우스는 금방 훈련의 기억을 잊고 어두운 방을 찾아가는 것에 비하여 고욤나무 추출물을 투여한 마우스는 더 오랜 시간을 기억하며 혹은 최대측정시간이 경과할 때까지 어두운 방을 찾아가지 아니하였다. 이러한 결과로 치매에 의한 인지능력 저하가 고욤 추출물에 의하여 효과적으로 저지됨을 확인하였다. 이러한 결과를 통해 고욤나무 추출물의 섭취가 치매로 인한 인지능력 저하를 효과적으로 보호해줄 수 있음을 확인하였다.As shown in FIG. 2, the mice that induced dementia remembered the memory of the training immediately and went to the dark room. However, the mice administered with guamoam extract remained for a longer time or until the maximum measurement time elapsed I did not find a dark room. As a result, it was confirmed that the cognitive impairment due to dementia was effectively inhibited by Goyom extract. These results suggest that the intake of Goatram extract can effectively protect the cognitive decline due to dementia.
아세틸콜린 Acetylcholine 에스터라제Estherazade 활성 저해 효과 Active inhibitory effect
평균 무게 25 g의 웅성 ICR 마우스를 세 군으로 임의로 분류하여 PBS 또는 고욤나무 추출물(50 ㎎/㎏) 또는 양성대조군인 타크린(tacrine; 10 ㎎/㎏)을 구강투여 하였으며, 투여 60분 후에 생쥐의 뇌를 적출하였다. 적출한 뇌에서 해마부위만을 잘라 차가운 RIPA 완충액를 첨가하여 균질화한 후 4℃ 하에서 10,000 g로 10분 동안 원심분리를 실시하여 상층액만 분석에 이용하였다. 아세틸콜린 에스터라제 활성은 이 등(Lee, B.; Jung, K.; Kim, D. H. Timosaponin AIII, a Saponin Isolated from Anemarrhena asphodeloides, Ameliorates Learning and Memory Impairments in Mice. Pharmacol ., Biochem . Behav . 2009, 93, 121127.)의 방법을 변형하여 이용하였다. 15 mM ATCh(25 ㎕), 3 mM DTNB(125 ㎕), 50 mM Tris-HCl (50 ㎕, pH 8.0)이 포함된 반응 혼합물과 분석 샘플을 마이크로플레이트에 넣고 10분 후, 아세틸콜린 에스터라제(0.226 U/㎖)를 추가적으로 넣었다. 그리고 ELISA 리더기 405 ㎚에서 10분 동안 스캔하였다. Bradford 단백질 분석 키트(Bio-Rad, Hercules, CA, U.S.)로 단백질 양을 정량한 후에 전체 단백질 양 ㎎ 당 아세틸콜린 에스터라제 활성으로 계산하였다.Male ICR mice with an average weight of 25 g were randomly divided into three groups and administered orally with PBS or goat extract (50 mg / kg) or tacrine (10 mg / kg) as a positive control. After 60 minutes of administration, Of the brain. In the extracted brain, only the hippocampal region was cut and homogenized by adding cold RIPA buffer. The supernatant was then centrifuged at 10,000 g for 10 minutes at 4 ° C. Acetylcholine esterase activity of the like (Lee, B .; Jung, K .; Kim, DH Timosaponin AIII, a Saponin Isolated from Anemarrhena asphodeloides, Ameliorates Learning and Memory Impairments in Mice. Pharmacol., Biochem. Behav. 2009, 93, 121127.). A reaction mixture containing 15 mM ATCh (25 μl), 3 mM DTNB (125 μl) and 50 mM Tris-HCl (50 μl, pH 8.0) was added to the microplate and after 10 minutes, the reaction mixture containing acetylcholinesterase (0.226 U / ml). And the ELISA reader was scanned at 405 nm for 10 minutes. The amount of protein was quantified with Bradford Protein Assay Kit (Bio-Rad, Hercules, Calif., USA) and then calculated as acetylcholinesterase activity per mg total protein.
그 결과, 도 3에서 확인할 수 있듯이 고욤나무 추출물이 우수한 아세틸콜린 에스터라제 저해 효과를 나타내는 것이 확인되었다. 이를 통해 고욤나무 추출물이 아세틸콜린 에스터라제 저해를 통해 치매를 효과적으로 예방 및 치료할 수 있음을 확인하였다. As a result, as shown in FIG. 3, it was confirmed that the Gomam extract had an excellent acetylcholinesterase inhibitory effect. It was confirmed that the extract of Goyomum can effectively prevent and treat dementia by inhibiting acetylcholinesterase inhibition.
실시예Example 3: 파킨슨병 예방 효과 3: Parkinson's disease prevention effect
진행성 파킨슨병 동물 모델의 구축Construction of an Advanced Model of Parkinson's Disease
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 등(Joo WS et al., Neuroreport, 9(18), 4123-4126, 1998)의 방법을 이용하여 동물모델을 다음과 같이 제작하였다.(Joo WS et al., Neuroreport, 1986), which induces progressive degeneration of dopamine neurons by injecting 6-hydroxydopamine (6-OHDA), widely used as a Parkinson's disease-inducing drug, into the striatum of the rat brain , 9 (18), 4123-4126, 1998), an animal model was prepared as follows.
체중 200-250 g의 웅성 스프라그-돌리계 랫트에 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 1>에서 제조한 고욤나무 추출물을 생리식염수에 희석하여 50 ㎎/㎏ 용량으로 20일 동안 매일 1회 복강주사로 투여하였다.Male Sprague-Dawley rats weighing 200-250 g were anesthetized by intraperitoneal injection of ketamine (100 mg / kg) and xylazine (50 mg / kg). Anesthetized animals were punctured using a stereotaxic frame (David Kopf, USA), and 0.2 ㎎ / ㎖ ascorbic acid was used in the sham group and dopamine hydroxylated in the
아포몰핀에Apomorphine 의한 by 일측성Unilateral 회전반응 실험 Rotational reaction experiment
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.Behavioral changes in Parkinson 's disease model using hydroxyapatite were investigated by subcutaneous injection of apomorphine (0.5 ㎎ / ㎏) on day 14 after lesion preparation and unilateral rotation reaction for 60 minutes Respectively.
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 측정기를 이용하였으며, 각 회전수는 [순 회전수(net turns) = 비병변측 회전수(contralateral) - 병변측 회전수(ipsilateral)]로 산출하였다.In this experiment, dopaminergic neurons were killed and the concentration of dopamine in the striatum was reduced, resulting in the hypersensitivity of the dopamine receptor in the striatum. Apomorphine acted as an agonist to the dopamine receptor, which exaggerated the irritable striatum (Ungerstedt, Brain Res. 24, 485-493, 2970). The rotational motion was measured using an automated rotational motion analyzer as described in Ungerstedt, supra, and the number of rotations was calculated as [net rotations = contralateral rotation (ipsilateral) - lesion side rotation number (ipsilateral)] Respectively.
그 결과, 도 4에서 보듯이 정상 대조군(Sham)의 일측성 순 회전수는 큰 변화를 보이지 않았으나, 수산화도파민만을 투여한 병변 대조군에서는 일측성 순회전수가 유의하게 증가되었다. 한편, 고욤나무 추출물을 함께 투여한 파킨슨병 모델에서는 병변 대조군에 비해 일측성 순 회전수가 감소하였다. 이로서 본 발명의 고욤나무 추출물이 파킨슨병 억제 효과가 있음을 확인하였다.As a result, as shown in FIG. 4, unilateral net revolutions of the normal control group (Sham) did not change greatly, but unilateral circulation was significantly increased in the lesion control group administered with only hydroxydopamine. On the other hand, in the Parkinson 's disease model in which Gomam tree extract was administered together, the unilateral net rotation number decreased compared to the lesion control group. Thus, it was confirmed that the Gomam extract of the present invention has an inhibitory effect on Parkinson's disease.
실시예Example 4: 허혈성 뇌질환 예방 효과 4: Ischemic brain disease prevention effect
허혈성 뇌질환 모델 제작 및 고욤나무 추출물의 투여Production of Ischemic Brain Disease Model and Administration of Guillaume Tree Extract
일시적인 중간목동맥 결찰(middle cerebral artery occlusion, MCAO)에 의한 뇌허혈성 뇌졸중 모델을 유도하여 고욤나무 추출물의 뇌 보호 및 치료 효과를 확인하는 실험을 수행하였다.A brain ischemic stroke model induced by temporal middle cerebral artery occlusion (MCAO) was conducted to confirm brain protection and therapeutic effects of the Koomomoe extract.
실험은 체중 220-270 g의 웅성 위스타(wistar) 랫트를 사용하였다. 실험용 쥐들은 12시간 간격으로 명암이 조절되는 사육실에서 실험 당일까지 정상적으로 물과 먹이를 섭취하도록 하였다. 실험 동물군은 sham, PBS 군 및 고욤나무 추출물 군으로 임의로 분류하였다. 복강 내로 케타민 80 ㎎/㎏ 및 럼푼(rumpun) 40 ㎎/㎏을 주사하여 마취하고 중간선 목절개 후 오른쪽 온목동맥을 노출시켜 신경과 근막을 분리하였다. 바깥 목동맥과 온목동맥을 5-0 견사 봉합사로 결찰하고 속목동맥은 주위에 위치한 미주신경을 분리하고 5-0 견사 봉합사로 느슨하게 결찰한 뒤, 5-0 나일론 봉합사(Ethicon, Johnson & Johnson, Somerville, NJ, USA)를 온목동맥의 갈림에서 속목동맥으로 18 ㎜ 넣어 90분 동안 막은 후 재관류를 실시하였다. 대조군(sham)은 동일하게 수술하되 중간대뇌동맥을 막지 않았다. 고욤나무 추출물군은 뇌허혈 유도 3일 전부터 <실시예 1>에서 제조한 고욤나무 추출물을 생리식염수에 희석하여 50 ㎎/㎏ 용량으로 20일 동안 매일 1회 복강주사로 투여하였다.Male wistar rats weighing 220-270 g were used. Experimental rats were allowed to consume water and food normally at 12-hour intervals from the control room to the experimental day. The experimental animals were randomly divided into sham, PBS, and Gomam tree extracts. Anesthesia was administered by intraperitoneal injection of
로타로드Rotarod 행동시험 Behavior test
MCAO(Middle Cerebral Artery Occlusion) 유도한 지 하루 뒤에 로타로드(rotarod) 시험을 실시하여 행동 변화로 뇌기능 손상 여부를 판단하였다. 로타로드 시험은 쥐를 회전하는 원통 위에서 달리게 하여 떨어지지 않고 머무는 시간을 측정하는 검사이다. 원통의 회전 속도는 6 rpm에서부터 19 rpm 까지 3분에 걸쳐 가속하였다. 실험에 사용한 쥐들은 모두 뇌졸중 모델 유도 전에 3일 동안 매일 원통 위에서 달리는 훈련을 하였다. 원통 위에서 달린 시간(latency time; 지연시간)은 세 번 반복 측정하여 평균값을 구하였다.The rotarod test was performed one day after the induction of MCAO (Middle Cerebral Artery Occlusion) to determine brain damage by behavioral changes. The RotaRoad test is a test that measures the length of time a rat rides on a spinning cylinder without falling. The rotational speed of the cylinder accelerated from 6 rpm to 19 rpm over 3 minutes. All of the rats in the experiment were trained to run on a cylinder daily for 3 days before stroke model induction. The latency time on the cylinder was measured three times and the mean value was obtained.
그 결과, 도 5에서 보는 바와 같이, MCAO 유도 전에는 회전하는 원통 위에서 쥐들이 180초까지 모두 버틸 수 있었지만 MCAO 유도한 지 하루 뒤에 실시한 로타로드 시험에서는 PBS를 주입한 군의 경우, 지연 시간이 현저하게 감소하였고, 일주일 뒤에도 동일시험에서 지연 시간이 150초로 큰 폭으로 회복되지 못하는 것을 확인하였다. 반면, 고욤나무 추출물군에서는 MCAO 유도 하루 뒤에도 150초 이상의 지연 시간을 보이고, 일주일 뒤에는 거의 정상 상태의 지연 시간을 보여 MCAO에 의한 뇌 손상 및 이로 인한 행동 변화가 회복된 것을 알 수 있었다.As a result, as shown in FIG. 5, mice were able to hold all the mice for 180 seconds on the rotating cylinder before MCAO induction. However, in the case of the group administered with PBS, the delay time was remarkably increased And the delay time was not recovered to 150 seconds in the same test after one week. On the other hand, in the cheomomoe extract group, the delay time was more than 150 seconds after the MCAO induction day, and almost a steady state delay time was observed after one week. Thus, it was found that the MCAO-induced brain damage and the behavioral change were restored.
신경학적 운동검사Neurological Exercise Test
신경학적 운동검사로는 시각과 위치감각 자극에 반응하는 앞발과 뒷발의 감각운동능력을 평가하는 검사인 체지배치 검사(Limb placing test)를 이용하였다.The neurological exercise test was performed using the Limb placing test, which is a test to evaluate the sensory ability of the front and rear hairs in response to visual and position sensory stimuli.
먼저 정방향 체지배치 검사(forward limb placing test)로 랫트의 꼬리를 잡고 공중으로 들어올린 후 양 앞다리의 신전 정도를 평가하여 점수화하였다. 정상적으로 양 앞발이 신전될 경우를 0점, 우측 앞다리가 비정상적으로 굴곡될 경우를 3점으로 하였다. 두 번째 검사로 측방향 체지배치 검사를 실시하였다. 쥐가 앞발을 자유로이 움직일 수 있도록 몸통을 잡아 든 뒤 지면과 수평을 이룬 상태로 테이블 옆에서 쥐를 테이블을 향해 가까이 가져가는 방법으로 검사하였다. 이때 쥐가 앞발을 옆으로 뻗어 테이블을 잡으려고 하면 정상 반응으로 판정하였다. 연속적으로 세 번 반복하여 세 번 모두 정상적인 반응을 보일 경우 0점, 세 번 중 한 번만 비정상 반응을 보일 경우 1점, 두 번만 비정상 반응을 보일 경우는 2점, 세 번 모두 비정상 반응을 보일 경우는 3점으로 계산하였다.First, the rats' tail was lifted with the forward limb placing test, and the degree of extension of the forelimb was assessed and scored. 0 point when the forepaw is normally extended, and 3 points when the right forepaw is flexed abnormally. The second test was a lateral body placement test. The rats were held by the body so that the paw could move freely, and then the rats were brought close to the table with the table horizontally. At this time, when the rat reached to the table with his forelegs extended sideways, normal reaction was judged. If there is an abnormality in all three times, three times in succession, it shows 0 point for normal reaction, 1 point for abnormality only once in 3 times, 2 points for abnormality in only 2 times, 3 points.
시험결과 도 6에서 보는 바와 같이, 뇌졸중을 유발하기 전에 측정한 경우 운동능력은 정상으로 신경손상 점수가 0에 가까웠지만 뇌졸중을 유발한 후 PBS 군에서는 15점 이상으로 크게 운동신경 손상이 나타난 것을 볼 수 있었던 반면, 고욤나무 추출물군의 경우 이러한 손상이 억제되고 있음을 확인할 수 있었다. 이는 뇌졸중 유발 후 일주일이 지난 후에도 여전히 유지되고 있어 고욤 추출물의 투여가 신경손상을 효과적으로 억제할 수 있음을 확인하였다.As shown in FIG. 6, as shown in FIG. 6, when measured before the stroke, the athletic ability was normal and the nerve damage score was close to zero. However, it was found that, in the PBS group after the stroke, Whereas it was found that the damage was suppressed in the Gomam tree extract group. It was confirmed that the administration of Goemon's extract effectively inhibited nerve damage because it still remained after a week after stroke induction.
실시예Example 5: 기억력 감퇴 예방 효과 5: Prevention of memory decline
기억력 감퇴 동물 모델 제작 및 고욤 추출물의 투여Preparation of animal model with memory loss and administration of goat's extract
무스카리닉(Muscarininc) 수용체의 길항체인 스코폴라민을 흰쥐에 투여하면 전시냅스(presynapse)에서 유리되는 신경전달물질인 아세틸콜린이 후시냅스(postsynapse)에 있는 그 수용체인 무스카리닉 수용체에 결합하여 정보전달을 하는 것을 일시적으로 차단하여 학습과 기억력을 손상시키게 되므로 스코폴라민을 투여하여 기억력감퇴 동물모델을 만들어 학습과 기억력 증진효과를 검증하는데 통상적으로 이용한다.When the scopolamine, an antagonist of the muscarinic receptor, is administered to rats, acetylcholine, a neurotransmitter liberated at presynapse, binds to muscarinic receptors, receptors in postsynaps, And thus it is commonly used to test learning and memory-enhancing effects by creating an animal model of memory loss by administering scopolamine.
본 발명에서는 고욤나무 추출물의 기억력 증진효과를 검증하기 위해 스코폴라민(Scopolamine) 1 ㎎/㎏을 마우스에 투여하여 기억력 감퇴 동물모델을 제작하였다. 그리고 스코폴라민 투여 2시간 후부터 <실시예 1> 에서 제조한 고욤나무 추출물을 생리식염수에 희석하여 50 ㎎/㎏ 용량으로 20일 동안 매일 1회 복강주사로 투여하였다.In the present invention, to examine the memory enhancing effect of Gomam tree extract, scopolamine (1 mg / kg) was administered to mice to prepare a memory decay animal model. After 2 hours from the administration of scopolamine, the extract of Guillaume extract prepared in Example 1 was diluted in physiological saline and administered by intraperitoneal injection once a day for 20 days at a dose of 50 mg / kg.
**
모리스의 Morris's 수중미로를Underwater maze 이용한 기억력 유지 시험 Used memory retention test
상기 <실시예 1>에서 얻은 고욤나무 추출물이 스코폴라민으로 기억력 감퇴를 유도한 실험 마우스의 기억력에 미치는 영향을 평가하기 위해, 상기 <실시예 2>의 마우스를 상대로 수중미로 실험을 시행하였다.In order to evaluate the effect of the gomam extract obtained in Example 1 on the memory of experimental mice induced to decline in memory by scopolamine, an underwater maze test was conducted on the mouse of Example 2 above.
모리스 수중미로 실험은 일반적으로 공간 능력 기억을 보는데 일반적으로 사용되는 실험이다. 실험방법은 둥그런 검은색 수조에 (60 ㎝ 직경; 40 ㎝ 깊이) 28±1℃ 물을 30 ㎝ 깊이만큼 채워 수조의 사면 중 한쪽 면에 플랫폼을 넣어두었다. 수조의 각기 다른 네 방향에서 실험동물을 넣어주고 수영하여서 플랫폼을 찾아가는데 걸리는 시간을 측정하였다. 플랫폼에 올라간 뒤 15초 동안 쉬게 한 후에 수조에서 건져주고 만일 300초가 넘어서도 플랫폼을 찾지 못하면, 동물이 플랫폼에 올라갈 수 있도록 실험자가 인도하여 주었다. 4일 동안 학습을 시키고 난 뒤에 하루를 쉬고 하고, 6일째에 다시 플랫폼까지 찾아가는데 걸리는 시간을 측정하였다(Manschot et al., Brain Res. 966(2) 274-282. 2003).The Morris Underwater Maze Experiment is a commonly used experiment to view spatial capacity memory in general. Experimental method was as follows: 28 ± 1 ℃ of water (60 ㎝ diameter; 40 ㎝ depth) into a round black water tank filled with water to a depth of 30 ㎝. We measured the time taken to put the animal in each of the four directions of the tank and to swim to find the platform. After reaching the platform, they rested for 15 seconds and then rescued from the tank. If the platform was not found after more than 300 seconds, the experimenter handed over the animal to the platform. Manschot et al., Brain Res., 966 (2) 274-282, 2003), and the time taken to return to the platform on the sixth day.
그 결과, 도 7에서 보는 바와 같이 스코폴라민에 의한 기억력 저하가 고욤나무 추출물에 의하여 효과적으로 저지됨을 확인하였다. 이러한 결과는 고욤나무 추출물이 기억력 감퇴 보호에 월등히 효과적임을 의미한다.As a result, as shown in FIG. 7, it was confirmed that the decline of memory by scopolamine was effectively inhibited by Gomam extract. These results suggest that the extracts of Goam yam extract are highly effective for the protection against memory loss.
실시예Example 6: 정상 동물에서 고욤 추출물의 기억력 및 인지기능 향상 효과 6: Improvement of memory and cognitive function of goomom extract in normal animals
수동회피능력시험Passive avoidance ability test
상기 <실시예 4>에서 실시한 동물 행동실험을 정상 마우스에서 동일하게 실시하였다. 단, 측정 최대 시간을 800초로 하였다.The animal behavioral tests conducted in Example 4 were performed in the same manner in normal mice. However, the maximum measurement time was 800 seconds.
상기 <실시예 1>의 고욤나무 추출물을 생리식염수에 희석하여 50 ㎎/㎏ 용량으로 20일 동안 매일 1회 복강주사로 투여한 후, 정상 쥐에서의 수동회피능력시험을 통한 기억력이 투여 전에 비해 증가한 것을 확인하였다(도 8). 이는 고욤나무 추출물은 정상 쥐에서도 기억력과 인지기능 개선에 효과가 있음을 확인한 것이다.The extract of Guomaum japonica extract of Example 1 was diluted in physiological saline and administered by intraperitoneal injection once daily for 20 days at a dose of 50 mg / kg. (Fig. 8). It was confirmed that Gomam extract was effective in improving memory and cognitive function in normal rats.
이상으로 본 발명의 특정한 부분을 상세히 기술하였는바, 당업계의 통상의 지식을 가진 자에게 있어서 이러한 구체적인 기술은 단지 바람직한 구현예일 뿐이며, 이에 본 발명의 범위가 제한되는 것이 아닌 점은 명백하다. 따라서 본 발명의 실질적인 범위는 첨부된 청구항과 그의 등가물에 의하여 정의된다고 할 것이다.While the present invention has been particularly shown and described with reference to exemplary embodiments thereof, it is to be understood that the same is by way of illustration and example only and is not to be construed as limiting the scope of the present invention. It is therefore intended that the scope of the invention be defined by the claims appended hereto and their equivalents.
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