KR20110119983A - Composition comprising extracts of mulberry fruits for inhibiting activity of acetylcholinesterase - Google Patents
Composition comprising extracts of mulberry fruits for inhibiting activity of acetylcholinesterase Download PDFInfo
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- KR20110119983A KR20110119983A KR1020100039443A KR20100039443A KR20110119983A KR 20110119983 A KR20110119983 A KR 20110119983A KR 1020100039443 A KR1020100039443 A KR 1020100039443A KR 20100039443 A KR20100039443 A KR 20100039443A KR 20110119983 A KR20110119983 A KR 20110119983A
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- extract
- mulberry fruit
- dementia
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Abstract
Description
본 발명은 뽕나무 열매 추출물을 유효성분으로 함유하는 아세틸콜린에스테라제(acetylcholinesterase) 억제용 조성물, 치매 예방 또는 치료용 조성물 및 치매 예방 또는 개선 효과를 나타내는 건강기능식품에 관한 것이다.The present invention relates to a composition for inhibiting acetylcholinesterase, a composition for preventing or treating dementia and a health functional food exhibiting an effect for preventing or improving dementia.
최근 생명과학 및 의학기술의 눈부신 발전은 인간의 평균 수명을 연장시키는 데 큰 기여를 하였다. 그러나 현대사회는 노령인구의 급증으로 인하여 노화에 따른 각종 퇴행성 질환들의 발생률이 급격히 증가하고 있고, 통계청(2005년 장래인구특별추계)에 따르면 우리나라는 2000년도에 고령화 사회에 진입했고 2026년도에는 초고령화 사회가 되어 노령인구의 증가에 따른 의료비 부담의 증가 등 사회적인 문제가 급격히 증가할 것으로 예상된다. 특히 뇌경색과 뇌출혈을 포함하는 뇌졸중(stroke)은 구미에서는 암과 심장질환에 이어 사망원인이 3위이고, 우리나라에서는 암에 이어 2위이다. 또한, 노인성 치매의 발명률은 65세 이상에서 5-10%, 70세 이상에서는 15%, 85세 이상에서는 24-45%로 나타나고 있으며, 현재 서구 사회에서는 65세 이상 인구의 약 10%, 80세 이상 인구의 약 40-50%가 알츠하이머성 치매를 앓고 있다. 우리나라 치매 환자의 수는 약 43만에서 56만 명으로 추정하고 있으며 그 수도 매년 증가하고 있는 추세이다.Recent remarkable advances in life sciences and medical technology have contributed significantly to prolonging human life expectancy. However, in the modern society, the incidence of various degenerative diseases due to aging is increasing rapidly due to the rapid increase of the elderly population, and according to the National Statistical Office (2005 Special Population Estimation), Korea entered an aging society in 2000 and became an aging population in 2026. As society becomes a society, social problems such as an increase in medical expenses due to an increase in elderly population are expected to increase rapidly. In particular, stroke including cerebral infarction and cerebral hemorrhage is the third leading cause of death after cancer and heart disease in Gumi and second place after cancer in Korea. In addition, the incidence of senile dementia is 5-10% in 65 and older, 15% in 70 and older, and 24-45% in 85 and older. About 40-50% of people over age have Alzheimer's dementia. The number of dementia patients in Korea is estimated at 430,000 to 560,000, and the number is increasing every year.
치매는 기억력 장애 및 판단력 상실 등의 전반적인 정신기능 장애를 초래하여 인간의 삶을 황폐하게 하는 질환이다. 치매의 원인은 다양한 편으로, 약 50%는 알츠하이머형 치매이고, 20-30%는 혈관성 치매, 알코올성 치매 또는 파킨슨병 치매 등이며, 약 15-20%는 알츠하이머형과 혈관성 치매 모두에 의한 것이다. 따라서 알츠하이머성 치매(Alzheimer’s disease;AD)는 치매의 유발 원인 중 가장 높은 비율을 차지하는 퇴행성 뇌신경질환으로, 발병원인이 정확하게 밝혀지지 않았지만 노화와 밀접한 관계가 있는 것으로 알려져 있지 않으나, 신경세포 손상이나 아세틸콜린 농도 저하에 의하여 발생되는 것으로 보고되고 있다. 신경세포 손상은 자유 라디칼, 글루타메이트, 칼슘 과다(calcium overload), 질소, 아밀로이드 베타 단백질 및 사이토카인 등의 다수 요인에 의하여 유발되며, 그 중에서 아밀로이드 베타(Aβ) 단백질의 과도한 축적이 가장 유력한 원인으로 보고되고 있다(Selkoe et al.,(1991), Beckman J. S., et al., (1990) Proc. Natl. Acad. Sci., 87:1620; Radi R., et al., (1991) Arch. Biochem. Biophys., 288, 481; Ljubuncic P., et al., (2000). GUT, 47(5), 710; Maria-Liisa S., et al., (2001) Cell Biol. lmmunol. Pathol. Intern Soc. Nephrol ., 59(2): 481). Dementia is a disease that depletes human life by causing mental disorders such as memory disorders and loss of judgment. There are various causes of dementia, with about 50% being Alzheimer's dementia, 20-30% being vascular dementia, alcoholic dementia or Parkinson's dementia, and about 15-20% being caused by both Alzheimer's and vascular dementia. Thus, Alzheimer's disease (AD) is the most common cause of dementia, a degenerative neurological disease. It is reported to be caused by a decrease in concentration. Neuronal damage is caused by a number of factors, including free radicals, glutamate, calcium overload, nitrogen, amyloid beta protein, and cytokines, among which excessive accumulation of amyloid beta (Aβ) protein is the most likely cause. (Selkoe et al., (1991), Beckman JS, et al., (1990) Proc. Natl. Acad. Sci., 87: 1620; Radi R., et al., (1991) Arch. Biochem. Biophys., 288, 481; Ljubuncic P., et al., (2000) .GUT, 47 (5), 710; Maria-Liisa S., et al., (2001) Cell Biol.lmmunol.Pathol.Intern Soc Nephrol, 59 (2): 481).
Aβ의 과도한 축적은 결과적으로 세포사멸(apoptosis)과 자유 라디칼(free radical)의 생성 및 염증 반응을 수반하여 결과적으로 신경세포의 산화적 손상으로 인해 세포가 파괴된다. 이러한 원인으로 알츠하이머성 치매 환자의 뇌 신경세포가 감소되며 신경전달물질인 acetylcholine(ACh)의 함량이 정상인의 것보다 감소되는 것으로 보고되고 있다(Hachiski et al., 1975). 아세틸콜린(acethylcholine: ACh)은 중추신경계 및 말초신경계에서의 신경전달물질로 알려져 있으며, 신경세포의 시냅스 크놉의 세포질에서 생합성되어 교감 또는 부교감 신경계의 시냅스 전 섬유 및 시냅스 후 섬유에서 분비되며, 부교감 신경섬유의 신경절후(post ganglion)에 존재하는 무스카린 수용체(muscarin receptor)에 자극(impulse) 신호를 반응시키고, 아세틸콜린에스테라제(acetylcholnesterase,AChE)에 의하여 분해된다. AChE에 의해 아세틸콜린은 콜린(choline)과 아세테이트(acetate)로 분해되는데, 분해되어진 콜린은 운반자(carrier)에 의해 다시 신경계로 부분 흡수되어진다. 이러한 과정을 cholinergic system이라고 하며 이 과정에 AChE가 결정적 역할을 한다. 치매 환자의 경우는 ACh의 양은 적은데 반해 AChE의 작용은 계속 유지되어 신경전달에 이상이 생기게 되면서 결국 학습 능력 및 기억력 감퇴와 인지력 저하 등과 같은 대표적인 치매의 병리현상이 발생하게 된다(Perry et al., 1997). Excessive accumulation of Αβ results in apoptosis and the production of free radicals and inflammatory reactions, resulting in cell destruction due to oxidative damage of neurons. For this reason, it has been reported that brain neurons in Alzheimer's dementia patients are reduced, and that the content of the neurotransmitter acetylcholine (ACh) is lower than that of normal persons (Hachiski et al., 1975). Acetylcholine (ACh) is known as a neurotransmitter in the central and peripheral nervous system, biosynthesized in the cytoplasm of synaptic knobs of neurons and secreted from presynaptic and postsynaptic fibers of the sympathetic or parasympathetic nervous system, and parasympathetic An impulse signal is reacted to the muscarin receptor present in the post ganglion of the fiber, and is degraded by acetylcholnesterase (AChE). Acetylcholine is broken down into choline and acetate by AChE, which is partially absorbed back into the nervous system by carriers. This process is called the cholinergic system and AChE plays a crucial role in this process. In patients with dementia, the amount of ACh is low, but AChE continues to function, leading to neurotransmission problems, leading to pathological symptoms of dementia such as learning ability, memory loss and cognitive decline (Perry et al., 1997).
따라서 아세틸콜린에스테라제 억제물질(acetylcholinesterase inhibitor)을 사용하여 치매를 예방 또는 치료할 수 있을 것으로 생각되고 있다. AChE는 신경전달물질 ACh을 퇴화시키는 효소이므로, AChE 억제제는 이 퇴화 과정을 억제함으로써 ACh 신경전달물질을 증가된 시간 동안 신경 클레프트(cleft)에 남게 하고 신경전달물질의 화학적 및 기능적 효과를 상승시켜, 기억력 증진 및 인지 작용을 향상시킬 수 있기 때문이다. Therefore, acetylcholinesterase inhibitors can be used to prevent or treat dementia. Since AChE is an enzyme that degrades the neurotransmitter ACh, AChE inhibitors inhibit this degradation process, leaving ACh neurotransmitters in the neural cleft for an increased time and increasing the chemical and functional effects of neurotransmitters. This is because it can improve memory and improve cognitive function.
현재까지 개발된 AChE 억제제로서 FDA의 승인을 받아 국내에서도 시판중인 약물로는 1,2,3,4-테트라히드로-9-아크리딘아민(1,2,3,4-tetrahydro-9-acridine amine; 타크린(tacrine)), 도네페질(Done Pezyl, E2020; 아리셉트(ARICEPT)), 리바스티그민(Rivastigmine, ENA713; 엑셀론(EXELON)), 갈란타민(galantamine), 코그넥스(Cognex)등이 있다. 이들 약품은 치매를 다스리는 작용기전이 중추신경전달계에 중심적인 역할을 하는 AChE의 활성억제를 통해 신경전달물질인 ACh의 농도를 증가시킴으로써 알츠하이머 질환을 예방 및 치료하는 약제로 알려지고 있다. 그러나 타크린은 가격이 매우 비싸며 간독성을 유발하여 장기적인 사용이 어려운 실정이고, 코그넥스(Cognex)의 경우 그 유효성분인 9-아미노-1,2,3,4-테트라히드로아크리딘(THA)이 경구 투여시 지각능력 향상의 소견을 보이기는 하지만(N. Engl. J. Med., 315, p1241, 1986), 떨림증, 어지럼증, 간 독성 등의 심각한 부작용을 수반하고 있어 널리 활용되지 못하고 있는 실정이다.As the AChE inhibitors developed so far, FDA approved the drug, which is commercially available in Korea as 1,2,3,4-tetrahydro-9-acridineamine (1,2,3,4-tetrahydro-9-acridine amine; tacrine, Done Pezyl, E2020; ARICEPT, rivastigmine, ENA713; EXELON, galantamine, Cognex, etc. have. These drugs are known as drugs to prevent and treat Alzheimer's disease by increasing the concentration of ACh, a neurotransmitter, through the inhibition of AChE activity, which plays a central role in the central nervous system. However, tacrine is very expensive and causes hepatotoxicity, making it difficult to use for a long time. In the case of Cognex, 9-amino-1,2,3,4-tetrahydroacridine (THA) is an active ingredient. Although oral administration has been shown to improve perception ability (N. Engl. J. Med., 315, p1241, 1986), it is not widely used due to serious side effects such as tremor, dizziness, and liver toxicity. to be.
이와 같이 종래의 치매 치료용 조성물의 경우 그 부작용이 가장 커다란 문제가 되고 있으며, 일부 화학적으로 합성된 아세틸콜린에스테라제 저해제가 개발 또는 시판중이나 심각한 부작용을 수반하여 문제가 되고 있어 이에 부작용을 최소화하면서 치매 예방 및 치료에 효과적인 천연자원의 개발이 절실히 요구되고 있는 실정이다.As such, the side effects of the conventional composition for treating dementia become the biggest problem, and some chemically synthesized acetylcholinesterase inhibitors are a problem with development or marketing or with serious side effects. The development of natural resources effective for the prevention and treatment of dementia is urgently needed.
그리하여 본 발명자들은 기존 조성물이 가진 부작용에 대한 우려가 없으면서도 아세틸콜린에스테라제의 효과적인 억제를 통한 치매 환자 특히, 알츠하이머성 치매 환자의 인지능력 개선 효능을 가진 식물소재를 도출하기 위해 다양한 식물을 대상으로 하여 연구를 수행하였다.Thus, the inventors of the present invention target various plants in order to derive plant material having an effect of improving the cognitive ability of dementia patients, particularly Alzheimer's dementia patients, through the effective suppression of acetylcholinesterase, without fear of the side effects of the existing composition. The study was carried out.
따라서 본 발명의 목적은 뽕나무 열매 추출물을 유효성분으로 함유하는 아세틸콜린에스테라제 억제용 조성물을 제공하는 것이다.Therefore, an object of the present invention is to provide a composition for inhibiting acetylcholinesterase containing the mulberry fruit extract as an active ingredient.
또한, 본 발명의 다른 목적은 뽕나무 열매 추출물을 유효성분으로 함유하는 치매 예방 또는 치료용 조성물을 제공하는 것이다.In addition, another object of the present invention to provide a composition for preventing or treating dementia, containing the mulberry fruit extract as an active ingredient.
또한, 본 발명의 다른 목적은 치매 예방 및 개선효과 또는 기억력 증진 효과를 나타내는 뽕나무 열매 추출물 및 식품학적으로 허용 가능한 식품보조 첨가제를 포함하는 건강기능식품을 제공하는 것이다.In addition, another object of the present invention is to provide a health functional food comprising a mulberry fruit extract and a food supplement acceptable food supplement additive exhibiting an effect of preventing and improving dementia or enhancing memory.
상기와 같은 본 발명의 목적을 달성하기 위해서, 본 발명은 뽕나무 열매 추출물을 유효성분으로 함유하는 아세틸콜린에스테라제 억제용 조성물을 제공한다.In order to achieve the object of the present invention as described above, the present invention provides a composition for inhibiting acetylcholinesterase containing the mulberry fruit extract as an active ingredient.
본 발명의 일실시예에 있어서, 상기 뽕나무 열매 추출물은 물, 유기용매 또는 물과 유기용매의 혼합용매를 이용해 추출하여 얻어질 수 있다.In one embodiment of the present invention, the mulberry fruit extract may be obtained by using water, an organic solvent or a mixed solvent of water and an organic solvent.
본 발명의 일실시예에 있어서, 상기 유기용매는 메탄올, 에탄올, 프로판올, 이소프로판올, 부탄올, 아세톤, 에테르, 벤젠, 클로로포름, 에틸아세테이트, 메틸렌클로라이드, 헥산 및 시클로헥산으로 이루어진 군중에서 선택될 수 있다.In one embodiment of the present invention, the organic solvent may be selected from the group consisting of methanol, ethanol, propanol, isopropanol, butanol, acetone, ether, benzene, chloroform, ethyl acetate, methylene chloride, hexane and cyclohexane.
또한, 본 발명은 뽕나무 열매 추출물을 유효성분으로 함유하는 치매 예방 또는 치료용 조성물을 제공한다.In addition, the present invention provides a composition for preventing or treating dementia, containing the mulberry fruit extract as an active ingredient.
나아가 본 발명은 치매 예방 및 개선 효과 또는 기억력 증진 효과를 나타내는 뽕나무 열매 추출물 및 식품학적으로 허용 가능한 식품 보조 첨가제를 포함하는 건강기능식품을 제공한다.Furthermore, the present invention provides a dietary supplement comprising a mulberry fruit extract and a food supplement acceptable food supplement additive exhibiting a dementia prevention and improvement effect or a memory enhancing effect.
본 발명의 뽕나무 열매 추출물은 탁월한 아세틸콜린에스테라제의 활성을 저해하는 효과를 나타내는바 이를 유효성분으로 포함하는 조성물은 체내에 대한 부작용도 없기 때문에 기억력 향상 및 치매 특히, 아세틸콜린의 감소를 나타내는 콜린성 신경기능 퇴화로 인한 알츠하이머성 치매의 치료 또는 예방에 유용한 약학적 용도로 사용할 수 있으며, 나아가 치매 증상을 개선할 수 있는 식품학적 용도로도 사용할 수 있다.The mulberry fruit extract of the present invention exhibits an excellent effect of inhibiting the activity of acetylcholinesterase, and the composition comprising it as an active ingredient has no side effects on the body, thus improving memory and dementia, in particular, a decrease in acetylcholine. It can be used as a pharmaceutical use for the treatment or prevention of Alzheimer's dementia due to neurodegeneration, and can also be used as a food use to improve dementia symptoms.
도 1은 뽕나무 열매의 물 추출물(MFH)과 에탄올 추출물(MFE)의 아세틸콜린에스테라제의 억제 활성을 나타낸 그래프이다.
도 2는 뽕나무 열매의 물 추출물(MFH)과 에탄올 추출물(MFE)의 DPPH 라디칼 소거 활성을 나타낸 그래프이다.
도 3은 뽕나무 열매의 물 추출물(MFH)과 에탄올 추출물(MFE)의 세포내 지질과산화 억제 활성을 나타낸 그래프이다.1 is a graph showing the inhibitory activity of acetylcholinesterase of water extract (MFH) and ethanol extract (MFE) of mulberry fruit.
Figure 2 is a graph showing the DPPH radical scavenging activity of the water extract (MFH) and ethanol extract (MFE) of mulberry fruit.
Figure 3 is a graph showing the intracellular lipid peroxidation inhibitory activity of the water extract (MFH) and ethanol extract (MFE) of mulberry fruit.
본 발명은 뽕나무 열매 추출물을 유효성분으로 함유하는 아세틸콜린에스테라제 억제용 조성물을 제공함에 그 특징이 있다. 일반적으로 아세틸콜린에스테라제 저해제는 알츠하이머성 질환을 치료하기 위한 치료제로 인식되고 있다. The present invention is characterized by providing a composition for inhibiting acetylcholinesterase containing the mulberry fruit extract as an active ingredient. In general, acetylcholinesterase inhibitors are recognized as therapeutic agents for the treatment of Alzheimer's disease.
뽕나무는 뽕나무과 뽕나무속의 낙엽 교목 또는 관목을 통틀어 이르는 말로, 동뽕나무, 몽고뽕나무, 꾸지뽕나무, 산뽕나무 등이 이에 속한다. 높이는 3~4미터이며, 잎은 어긋나고 끝이 뾰족한 달걀 모양인데 가장자리에 톱니가 있다. 암수딴그루 또는 암수한그루로 봄에 잎겨드랑이에 누런 녹색의 꽃이삭이 달리고, 잎은 누에의 사료로 쓰고 나무껍질은 노란색 염료, 목재는 가구재로 쓴다. 북반구의 온대, 난대에 약 35종이 분포하는데 한국(중부지방)과 중국에서 주로 재배하며, 우리나라에서는 예로부터 밭둑이나 산골짜기에 많이 심었고 산상(山桑), 노상(魯桑), 백상(白桑)의 세 종이 재배된다. Mulberry is a word that leads to the entire deciduous tree or shrub of the mulberry and mulberry, such as dong mulberry, Mongolia mulberry, cooji mulberry, mountain mulberry. Its height is 3 ~ 4m, leaves are alternate, pointed egg-shaped with serration on the edge. Male and female, with yellowish green flowers on leaf axle in spring, leaves are used for silkworms, bark is yellow dye, and wood is used for furniture. About 35 species are distributed in the temperate and ovarian regions of the Northern Hemisphere, mainly grown in Korea (Central Region) and China. In Korea, they have been planted in field banks and valleys since ancient times. Iii) three species are grown.
흔히 오디라고 불리는 뽕나무의 열매는 자줏빛을 띤 검은색의 핵과로 6월 무렵에 맺는데, 상실(桑實)·또는 오들개라고도 한다. 지름 약 2cm로서 처음에는 녹색이다가 검은빛을 띤 자주색으로 익는다. 익으면 즙이 풍부해지며, 당분이 들어 있어 새콤달콤하고 신선한 향기가 나 주로 날로 먹거나 술 또는 주스를 담가 먹는다. 포함된 성분으로는 포도당과 과당, 시트르산, 사과산, 타닌,·펙틴을 비롯하여 비타민(A B1 B2 D), 칼슘, 인, 철 등이 들어 있다. 강장제로 알려져 있으며 내장, 특히 간장과 신장의 기능을 좋게 하는 것으로 알려져 있다. 또한 관절을 부드럽게 하며 마음을 편안하게 하여 불면증과 건망증에도 효과가 있으며, 혈당과 콜레스테롤 저하 효과도 있다고 알려져 있다. 또한 머리가 세는 것을 막아 주고 조혈작용이 있어 류머티즘 치료에도 쓰이고 있다.The fruit of the mulberry tree, commonly called audi, is a purplish black nucleus that forms in June. It is also called a loss or odal. It is about 2cm in diameter, green at first, and then ripened into blackish purple. When it is ripe, it is rich in juice and contains sweet and sour scents, usually eaten raw or soaked in alcohol or juice. Included ingredients include glucose, fructose, citric acid, malic acid, tannin, and pectin, as well as vitamins (A B1 B2 D), calcium, phosphorus and iron. Known as a tonic, it is known to improve the function of the intestines, especially the liver and kidneys. It also softens the joints and relaxes the mind, which is effective for insomnia and forgetfulness, and is known to lower blood sugar and cholesterol. It also prevents the head from counting and has a hematopoietic effect, which is used to treat rheumatism.
이에 본 발명자들은 뽕나무 열매를 이용한 약제를 연구하던 중 뽕나무 열매에서 추출한 추출물이 아세틸콜린을 가수분해하는 아세틸콜린에스테라제의 활성을 저해한다는 사실을 확인하고, 상기 뽕나무 열매 추출물이 치매를 예방 또는 치료할 수 있다는 사실을 규명하였다.Therefore, the present inventors confirm that the extract extracted from the mulberry fruit inhibits the activity of acetylcholinesterase hydrolyzing acetylcholine during the study of the drug using the mulberry fruit, the mulberry fruit extract to prevent or treat dementia Proved to be possible.
본 발명에 사용되는 원료인 뽕나무 열매 오디는 가능한 꼭지가 신선하고 통통한 것을 고르되 겉은 검은색으로 무르지 않고, 짙은 보라색인 것을 채취하여 사용하는 것이 좋다.Mulberry fruit mulberry used as a raw material for the present invention is to choose as fresh and plump as possible taps, but the outside is not smooth black, it is good to use a dark purple one.
본 발명의 뽕나무 열매 추출물은 물 이나 유기용매, 또는 이들의 혼합용매를 이용하여 본 발명이 속하는 기술 분야의 당업자에게 알려진 정제 방법을 이용하여 추출 및 정제될 수 있다. Mulberry fruit extract of the present invention can be extracted and purified using a purification method known to those skilled in the art to which the present invention belongs using water or an organic solvent, or a mixed solvent thereof.
상기 추출을 위한 적절한 용매로는 정제수, 메탄올(methanol), 에탄올(ethanol), 프로판올(propanol), 이소프로판올(isopropanol), 부탄올(butanol), 아세톤(acetone), 에테르(ether), 벤젠(benzene), 클로로포름(chloroform), 에틸아세테이트(ethyl acetate), 메틸렌클로라이드(methylene chloride), 헥산(hexane) 및 시클로헥산(cyclohexane) 등의 각종 용매를 단독으로 혹은 혼합하여 사용할 수 있으며, 보다 바람직하게는 에탄올을 사용할 수 있다. Suitable solvents for the extraction include purified water, methanol (methanol), ethanol (ethanol), propanol, isopropanol (isopropanol), butanol, acetone (acetone), ether (ether), benzene, Various solvents such as chloroform, ethyl acetate, methylene chloride, hexane and cyclohexane may be used alone or in combination. More preferably, ethanol may be used. Can be.
본 발명의 뽕나무 열매 추출물은 통상의 추출물의 제조방법에 따라 제조된 것일 수 있으며, 구체적으로는 냉침추출법, 온침추출법 또는 열수 추출법 등일 수 있으며, 통상의 추출기기, 초음파분쇄 추출기 또는 분획기를 이용할 수 있다. 또한, 상기 용매로 추출한 추출물은 이후, 여과하거나 농축 또는 건조과정을 수행하여 용매를 제거할 수 있으며, 여과, 농축 및 건조를 모두 수행할 수 있다. 구체적으로 상기 여과는 여과지를 이용하거나 감압여과기를 이용할 수 있으며, 상기 농축은 감압 농축기, 일예로 회전 증발기를 이용하여 감압 농축할 수 있으며, 상기 건조는 일예로 동결건조법으로 수행할 수 있다. 또한, 상기 수득한 뽕나무 열매 추출물은 사용 시까지 급속 냉동 냉장고(deep freezer)에 보관할 수 있고, 농축 및 동결건조를 통하여 수분을 완전히 제거시킬 수 있으며, 상기 수분을 완전히 제거시킨 뽕나무 열매 추출물은 분말형태로 사용하거나 상기 분말을 증류수 또는 통상의 용매에 녹여 사용할 수 있다.Mulberry fruit extract of the present invention may be prepared according to a conventional method for producing a extract, specifically may be cold extraction, hot extraction or hot water extraction, etc., may be used a conventional extraction device, ultrasonic grinding extractor or fractionator. . In addition, the extract extracted with the solvent may then remove the solvent by performing a filtration or concentration or drying process, it can be carried out both filtration, concentration and drying. Specifically, the filtration may be performed using a filter paper or a reduced pressure filter, the concentration may be concentrated under reduced pressure using a reduced pressure concentrator, for example, a rotary evaporator, and the drying may be performed by, for example, a lyophilization method. In addition, the obtained mulberry fruit extract can be stored in a deep freezer until use, can be completely removed moisture through concentration and lyophilization, the mulberry fruit extract completely removed the moisture is powder form It may be used as or the powder is dissolved in distilled water or a common solvent.
구체적으로 본 발명의 뽕나무 열매 추출물은 하기와 같이 수득될 수 있다. 채집한 뽕나무 열매를 동결 건조하여 마쇄한 후 뽕나무 열매 오디의 분말 시료 중량의 약 2 내지 15배, 바람직하게는 약 5 내지 10배에 달하는 부피의 물이나 메탄올, 에탄올, 부탄올과 같은 C1 내지 C4의 저급 알콜 또는 이들의 약 1:0.1 내지 1:10의 혼합비를 갖는 혼합용매, 바람직하게는 70 내지 100%의 에탄올로 실온에서 약 1시간 내지 1일, 바람직하게는 6시간 내지 12시간 동안 열수 추출, 냉침 추출, 환류 냉각 추출 또는 초음파 추출, 바람직하게는 열수 추출하여 감압여과 및 농축해 본 발명의 뽕나무 열매 추출물을 수득할 수 있다.Specifically, the mulberry fruit extract of the present invention can be obtained as follows. After freeze-drying the collected mulberry fruit and crushed, the volume of water of about 2 to 15 times, preferably about 5 to 10 times the weight of the powder sample of mulberry fruit mulberry, C 1 to C such as methanol, ethanol and butanol A lower alcohol of 4 or a mixed solvent having a mixing ratio of about 1: 0.1 to 1:10, preferably 70 to 100% ethanol, at room temperature for about 1 to 1 day, preferably 6 to 12 hours Hot water extraction, cold needle extraction, reflux cooling extraction or ultrasonic extraction, preferably hot water extraction, under reduced pressure filtration and concentration can be obtained mulberry fruit extract of the present invention.
본 발명의 일실시예에 따르면, 뽕나무 열매 추출물이 아세틸콜린에스테라제의 활성을 저하시킬 수 있는 효과가 있는지를 조사하기 위해 뽕나무 열매를 에탄올과 정제수를 추출용매로 하여 얻은 물 추출물(MFH) 및 에탄올 추출물(MFE)의 아세틸콜린에스케라제 저해 활성을 Ellman et al.(1961)의 방법에 준하여 측정하였다. 그 결과 뽕나무 열매의 물 추출물 및 에탄올 추출물 모두에서 농도 의존적으로 아세틸콜린에스테라제에 대한 저해 활성이 유의적으로 증가하는 것으로 나타났다(도 1 참조).According to one embodiment of the present invention, in order to investigate whether the mulberry fruit extract has an effect of reducing the activity of acetylcholinesterase, the water extract (MFH) obtained from the mulberry fruit using ethanol and purified water as an extraction solvent, and Acetylcholineeskerase inhibitory activity of ethanol extract (MFE) was measured according to the method of Ellman et al. (1961). As a result, the inhibitory activity against acetylcholinesterase was significantly increased in both water extract and ethanol extract of mulberry fruit (see FIG. 1).
또한 아세틸콜린의 농도저하 이외의 또 다른 치매의 원인으로 지적되고 있는 신경세포 손상은 지질과산화(lipid peroxidation)의 대사과정에 생성되는 자유 라디칼(free radical)에 의해 야기된다고 보고되고 있는바, 본 발명에 따른 뽕나무 열매 추출물은 이와 관련하여 아세틸콜린에스테라제의 억제활성 뿐만 아니라 지질과산화 및 자유라디칼의 생성을 억제하는 항산화력 또한 지니고 있다. In addition, neuronal damage, which has been pointed out as another cause of dementia other than lowering the concentration of acetylcholine, is reported to be caused by free radicals generated during the metabolic process of lipid peroxidation. The mulberry fruit extract according to the present invention has antioxidant activity to inhibit lipid peroxidation and production of free radicals as well as inhibitory activity of acetylcholinesterase.
본 발명의 일실시예에 따르면 본 발명자들은 뽕나무 열매 추출물의 신경세포의 손상을 억제할 수 있는 항산화력에 대한 실험 또한 수행하였는데, 우선 자유라디칼의 소거 활성을 확인하기 위해 DPPH 라디칼 소거법을 이용하였다. DPPH 라디칼은 안정한 자유 라디칼로 다른 원자 및 분자로부터 전자나 양성자를 받아들여 안정한 분자로 변하는 성질이 있는바(Soares et al., 1997), 비교적 빠른 시간에 자유 라디칼의 소거 활성을 측정할 수 있어 DPPH 라디칼 소거 활성 모델은 널리 사용되고 있다. 본 방법은 DPPH 라디칼의 보라색이 항산화제가 존재할 경우 노란색으로 변화해 육안으로 쉽게 확인할 수 있기 때문에 항산화 활성 측정에 자주 이용되는데, 본 발명에 따른 뽕나무 열매의 물 추출물 및 에탄올 추출물의 DPPH 소거 활성을 측정한 결과 두 추출물 모두에서 높은 농도 의존적인 소거 활성이 나타났다. 구체적으로는 에탄올 추출물(MFE)이 물 추출물(MFH) 보다 조금 높은 소거활성을 보였는데, 이는 에탄올을 이용하여 추출물을 제조할 경우 극성 물질 뿐만 아니라 비극성 물질의 항산화제도 같이 추출되기 때문인 것으로 판단된다(도 2 참조).According to one embodiment of the present invention, the present inventors also carried out an experiment on the antioxidant power that can inhibit the damage of neurons of the mulberry fruit extract, first used DPPH radical scavenging method to confirm the scavenging activity of free radicals. DPPH radicals are stable free radicals that accept electrons or protons from other atoms and molecules and become stable molecules (Soares et al., 1997). DPPH radicals can be used to measure the scavenging activity of free radicals in a relatively short time. Radical scavenging activity models are widely used. This method is often used to measure the antioxidant activity of the purple purple of the DPPH radical is changed to yellow in the presence of an antioxidant, and the DPPH scavenging activity of the water extract and the ethanol extract of the mulberry fruit according to the present invention was measured. Results Both concentrations showed high concentration dependent scavenging activity. Specifically, the ethanol extract (MFE) showed a slightly higher scavenging activity than the water extract (MFH), which is considered to be due to the extraction of antioxidants of non-polar substances as well as polar substances when the extract is prepared using ethanol ( 2).
또한 불포화 지방산은 자유 라디칼에 의한 주요한 산화 대상이 되는 물질로본 발명의 일실시예에 따르면, 본 발명에 따른 뽕나무 열매 추출물의 세포막 지질 산화 억제 정도를 확인하기 위해 쥐의 RAW264.7 세포에 형광물질인 DPPP를 처리한 다음 강력한 알킬 라디칼 제네레이터(alkyl radical generator)인 AAPH에 의해 생성되는 과산화된 지질의 함량을 측정하였다. DPPP는 그 자체로 형광을 나타내지 않으나 하이드로퍼옥사이드에 의해 산화된 DPPP 옥사이드(oxide)는 높은 형광을 나타내기 때문이다. 그 결과, 뽕나무 열매 추출물을 첨가한 군에서는 지질과산화를 억제하여 DPPP 옥사이드 형광강도(fluorescence intensity)가 농도 의존적으로 감소함을 알 수 있었다(도 3 참조).In addition, the unsaturated fatty acid is a major oxidizing substance by free radicals. According to one embodiment of the present invention, a fluorescent substance is used in RAW264.7 cells of rats to confirm the degree of inhibition of cell membrane lipid oxidation of the mulberry fruit extract according to the present invention. Phosphorus DPPP was then treated to determine the content of peroxidized lipids produced by AAPH, a powerful alkyl radical generator. DPPP does not fluoresce itself, but DPPP oxide oxidized by hydroperoxide shows high fluorescence. As a result, in the group to which the mulberry fruit extract was added, it was found that DPPP oxide fluorescence intensity was reduced in a concentration-dependent manner by inhibiting lipid peroxidation (see FIG. 3).
따라서 아세틸콜린을 가수분해하는 아세틸콜린에스테라제(AChE)의 작용을 차단함으로서 내생의(endogenous) 아세틸콜린의 함량을 높여주는 아세틸콜린에스테라제 저해제는 결과적으로 알츠하이머성 치매 환자의 뇌에서 콜린에 의한 신경전달(cholinergin neurotransmission)을 향상시키는 역할을 하므로(Yu et al., 1999), 본 발명자들은 상기 결과를 통해 뽕나무 열매 추출물이 아세틸콜린에스테라제의 활성을 저해시켜 아세틸콜린의 부족으로 인해 발생하는 치매 질환을 예방 또는 치료할 수 있다는 사실을 확인하였으며, 더불어 본 발명에 따른 뽕나무 열매 추출물은 또 다른 활성인 지질과산화 억제 및 자유 라디칼 소거효과와 같은 항산화활성에 의해 신경세포의 손상 까지도 억제하므로, 본 발명은 치매 질환을 보다 효과적으로 예방 또는 치료할 수 있어 기억력 및 인지능력 향상의 효과를 나타낼 수 있음을 확인하였다.Therefore, acetylcholinesterase inhibitors that increase the content of endogenous acetylcholine by blocking the action of acetylcholinesterase (AChE), which hydrolyzes acetylcholine, result in choline in the brain of Alzheimer's dementia patients. (Yu et al., 1999), the present inventors found that the mulberry fruit extract inhibited the activity of acetylcholinesterase and caused by the lack of acetylcholine, because it plays a role of improving cholinergin neurotransmission. It has been confirmed that the dementia disease can be prevented or treated, and the mulberry fruit extract according to the present invention also inhibits damage to nerve cells by antioxidant activity, such as inhibiting lipid peroxidation and free radical scavenging effect, which is another active, Invention can more effectively prevent or treat dementia It was confirmed that can represent the effect of improving cognitive ability.
그러므로 본 발명은 뽕나무 열매 추출물을 유효성분으로 함유하는 아세틸콜린에스테라제 억제용 조성물을 제공할 수 있으며, 더불어 치매 예방 또는 치료용 조성물을 제공할 수 있다. Therefore, the present invention can provide a composition for inhibiting acetylcholinesterase containing the mulberry fruit extract as an active ingredient, and can also provide a composition for preventing or treating dementia.
본 발명에서의 상기 치매는 바람직하게는 아세틸콜린의 감소를 포함하는 콜린성 신경기능 퇴화로 인한 알츠하이머성 치매일 수 있다.The dementia in the present invention may preferably be Alzheimer's dementia due to cholinergic neurodegeneration, including a decrease in acetylcholine.
또한, 본 발명에 따른 아세틸에스테라제 억제용 조성물은 뽕나무 열매 추출물을 단독으로 포함하거나 하나 이상의 약학적으로 허용되는 담체, 부형제 또는 희석제를 포함할 수 있다. 상기에서 약학적으로 허용되는이란 생리학적으로 허용되고 인간에게 투여될 때, 통상적으로 위장 장애, 현기증과 같은 알레르기 반응 또는 이와 유사한 반응을 일으키지 않는 조성물을 말한다. 상기 담체, 부형제 및 희석제의 예로는, 락토즈, 덱스트로즈, 수크로즈, 솔비톨, 만니톨, 자일리톨, 에리스리톨, 말티톨, 전분, 아카시아 고무, 알지네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실리케이트, 셀룰로즈, 메틸 셀룰로즈, 폴리비닐피롤리돈, 물, 메틸하이드록시벤조에이트, 프로필하이드록시벤조에이트, 탈크, 마그네슘 스테아레이트 및 광물유를 들 수 있으며 충진제, 항응집제, 윤활제, 습윤제, 향료, 유화제 및 방부제 등을 추가로 포함할 수 있다. In addition, the composition for inhibiting acetylesterase according to the present invention may include mulberry fruit extract alone or may include one or more pharmaceutically acceptable carriers, excipients or diluents. Pharmaceutically acceptable herein refers to a composition that is physiologically acceptable and, when administered to a human, typically does not cause an allergic reaction, such as gastrointestinal disorders, dizziness, or the like. Examples of such carriers, excipients and diluents include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, Polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil, and further include fillers, anticoagulants, lubricants, wetting agents, fragrances, emulsifiers and preservatives. can do.
또한, 본 발명의 조성물은 포유동물에 투여된 후 활성 성분의 신속, 지속 또는 지연된 방출을 제공할 수 있도록 약제학적 분야의 통상적인 방법에 따라 주사제, 액상제, 환제, 정제, 캅셀제, 산제 및 현탁제 등의 제제로 제형화될 수 있다. 제형은 분말, 과립, 정제, 에멀젼, 시럽, 에어로졸, 연질 또는 경질 젤라틴 캅셀, 멸균 주사용액, 멸균 분말의 형태일 수 있으며, 바람직하게는 정제, 캅셀제, 또는 액상제이다.In addition, the compositions of the present invention are injectables, liquids, pills, tablets, capsules, powders and suspensions according to conventional methods in the pharmaceutical art so as to provide rapid, sustained or delayed release of the active ingredient after administration to a mammal. It may be formulated into a formulation such as agent. The formulations may be in the form of powders, granules, tablets, emulsions, syrups, aerosols, soft or hard gelatin capsules, sterile injectable solutions, sterile powders, preferably tablets, capsules, or liquids.
본 발명에 따른 치매 예방 또는 치료용 조성물은 경구, 경피, 피하, 정맥 또는 근육을 포함한 여러 경로를 통해 투여될 수 있으며, 활성 성분의 투여량은 투여 경로, 환자의 연령, 성별, 체중 및 환자의 중증도 등의 여러 인자에 따라 적절히 선택될 수 있다. 그러나 바람직한 효과를 위해서, 본 발명의 추출물은 1일 0.0001 내지 100㎎/㎏으로, 바람직하게는 0.001 내지 100㎎/㎏으로 투여하는 것이 좋다. 투여는 하루에 한번 투여할 수도 있고, 수회 나누어 투여할 수도 있다. 상기 투여량은 어떠한 면으로든 본 발명의 범위를 한정하는 것은 아니다. 또한, 본 발명의 조성물은 치매를 예방, 개선 또는 치료하는 효과를 가지는 공지의 화합물과 병행하여 투여할 수 있다.The composition for preventing or treating dementia according to the present invention may be administered through various routes including oral, transdermal, subcutaneous, intravenous or intramuscular, and the dosage of the active ingredient is determined by the route of administration, age, sex, weight and It may be appropriately selected depending on various factors such as severity. However, for the preferred effect, the extract of the present invention is preferably administered at 0.0001 to 100 mg / kg, preferably 0.001 to 100 mg / kg per day. Administration may be administered once a day or may be divided several times. The dosage does not limit the scope of the invention in any aspect. In addition, the composition of the present invention can be administered in parallel with known compounds having the effect of preventing, improving or treating dementia.
따라서 본 발명은 뽕나무 열매 추출물을 유효성분으로 함유하는 조성물을 포함하는 치매의 증상을 예방 및 치료할 수 있는 약제를 제공할 수 있다.Therefore, the present invention can provide a medicament capable of preventing and treating the symptoms of dementia, including a composition containing the mulberry fruit extract as an active ingredient.
본 발명에 따른 조성물은 화합적으로 합성한 화합물이 아닌 천연물로서 뽕나무 열매 추출물을 유효성분으로 하는 조성물인바 약물에 대한 독성 및 부작용도 없어 장기간 복용 시에도 안심하고 사용할 수 있으며, 체내에 대해 매우 안정하다는 특징이 있다.The composition according to the present invention is not a compound synthesized synthetically is a natural product as a composition that contains the mulberry fruit extract as an active ingredient, there is no toxicity and side effects on the drug can be used safely even for long-term use, it is very stable to the body There is a characteristic.
나아가 본 발명의 치매의 예방 또는 치료용 조성물은 상기 기술한 바와 같이 치매의 증상을 예방 또는 치료하기 위한 목적으로 약학적 조성물로 사용할 수 있을 뿐만 아니라, 치매 증상의 예방 및 개선 또는 기억력 증진 효과를 나타내는 건강기능식품의 제조를 위한 식품용 조성물로 사용할 수 있다.Furthermore, the composition for the prevention or treatment of dementia of the present invention can be used as a pharmaceutical composition for the purpose of preventing or treating the symptoms of dementia as described above, and also exhibits the effect of preventing and improving dementia symptoms or enhancing memory. It can be used as a composition for food for the manufacture of health functional food.
그러므로 본 발명의 식품용 조성물은 치매 증상의 예방 및 개선 또는 기억력 증진 효과가 있는 식품, 예컨대, 식품의 주원료, 부원료, 식품 첨가제, 기능성 식품 또는 음료로 용이하게 활용할 수 있다.Therefore, the composition for food of the present invention can be easily utilized as a food, such as a main ingredient, an auxiliary ingredient, a food additive, a functional food, or a beverage having an effect of preventing and improving dementia or improving memory.
본원에서 상기 “식품”이란, 영양소를 한 가지 또는 그 이상 함유하고 있는 천연물 또는 가공품을 의미하며, 바람직하게는 어느 정도의 가공 공정을 거쳐 직접 먹을 수 있는 상태가 된 것을 의미하며, 통상적인 의미로서, 식품, 식품 첨가제, 기능성 식품 및 음료를 모두 포함하는 것을 말한다. As used herein, the term “food” refers to a natural product or processed product containing one or more nutrients, and preferably means a state in which it can be directly eaten through a certain processing step, It includes all foods, food additives, functional foods and drinks.
본원발명에 따른 치매 증상의 예방 및 개선 또는 기억력 증진용 조성물을 첨가할 수 있는 식품으로는 예를 들어, 각종 식품류, 음료, 껌, 차, 비타민 복합제, 기능성 식품 등이 있다. 추가로, 본원발명에서 식품에는 특수영양식품(예, 조제유류, 영,유아식 등), 식육가공품, 어육제품, 두부류, 묵류, 면류(예, 라면류, 국수류 등), 빵류, 건강보조식품, 조미식품(예, 간장, 된장, 고추장, 혼합장 등), 소스류, 과자류(예, 스넥류), 캔디류, 쵸코렛류, 껌류, 아이스크림류, 유가공품(예, 발효유, 치즈 등), 기타 가공식품, 김치, 절임식품(각종 김치류, 장아찌 등), 음료(예, 과실 음료, 채소류 음료, 두유류, 발효음료류 등), 천연조미료(예, 라면 스프 등)을 포함하나 이에 한정되지 않는다. 상기 식품, 음료 또는 식품첨가제는 통상의 제조방법으로 제조될 수 있다. Foods to which a composition for preventing and improving dementia symptoms or enhancing memory according to the present invention can be added include, for example, various foods, beverages, gums, teas, vitamin complexes, and functional foods. In addition, in the present invention, food includes special nutritional products (e.g., formulated milk, young, infant food, etc.), processed meat products, fish products, tofu, jelly, noodles (e.g. ramen, noodles, etc.), bread, health supplements, seasonings. Foods (e.g. soy sauce, miso, red pepper paste, mixed soy sauce), sauces, confectionery (e.g. snacks), candy, chocolates, gums, ice creams, dairy products (e.g. fermented milk, cheese, etc.), other processed foods, kimchi, Pickled foods (various kimchi, pickles, etc.), beverages (e.g., fruit drinks, vegetable drinks, soy milk, fermented beverages, etc.), natural seasonings (e.g. ramen soup, etc.) are not limited thereto. The food, beverage or food additive may be prepared by a conventional production method.
또한, 상기 “기능성 식품”이란 식품에 물리적, 생화학적, 생물공학적 수법 등을 이용하여 해당 식품의 기능을 특정 목적에 작용, 발현하도록 부가가치를 부여한 식품군이나 식품 조성이 갖는 생체방어리듬조절, 질병방지와 회복 등에 관한 체내조절기능을 생체에 대하여 충분히 발현하도록 설계하여 가공한 식품을 의미하며, 구체적으로는 건강 기능성 식품일 수 있다. 상기 기능성 식품에는 식품학적으로 허용 가능한 식품 보조 첨가제를 포함할 수 있으며, 기능성 식품의 제조에 통상적으로 사용되는 적절한 담체, 부형제 및 희석제를 더욱 포함할 수 있다. In addition, the term "functional food" refers to the control of biological defense rhythms and disease prevention of food groups or food compositions that have added value to the food by using physical, biochemical, or biotechnological techniques to act and express the function of the food for a specific purpose. It means a food that is designed and processed to fully express the body's regulatory function regarding recovery and the like, and specifically, it may be a health functional food. The functional food may include food acceptable food additives, and may further include appropriate carriers, excipients and diluents commonly used in the manufacture of functional foods.
또한, 본원발명에서 상기“음료”란 갈증을 해소하거나 맛을 즐기기 위하여 마시는 것의 총칭을 의미하며 기능성 음료를 포함한다. 상기 음료는 지시된 비율로 필수 성분으로서 상기 치매 증상의 예방 및 개선 또는 기억력 증진용 조성물을 포함하는 것 외에 다른 성분에는 특별한 제한이 없으며 통상의 음료와 같이 여러 가지 향미제 또는 천연 탄수화물 등을 추가 성분으로서 함유할 수 있다. In addition, in the present invention, the "beverage" refers to a generic term for drinking to quench thirst or to enjoy a taste and includes a functional drink. The beverage is an essential ingredient in the ratio indicated, and includes no composition for preventing and improving the symptoms of dementia or improving memory, and there are no special restrictions, and various ingredients such as ordinary drinks or natural carbohydrates may be added. It may contain as.
또한, 상기 기술한 것 이외에 본원발명의 치매 증상의 예방 및 개선 또는 기억력 증진용 조성물을 함유하는 식품은 여러 가지 영양제, 비타민, 광물(전해질), 합성 풍미제 및 천연 풍미제 등의 풍미제, 착색제 및 충진제(치즈, 초콜릿 등), 펙트산 및 그의 염, 알긴산 및 그의 염, 유기산, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알코올, 탄산 음료에 사용되는 탄산화제 등을 함유할 수 있으며, 상기 성분은 독립적으로 또는 조합하여 사용할 수 있다. In addition, foods containing a composition for preventing and improving dementia or improving memory of the present invention, in addition to those described above, may include various nutrients, vitamins, minerals (electrolytes), synthetic flavors, and natural flavoring agents, and colorants. And fillers (cheese, chocolate, etc.), pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloidal thickeners, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, carbonation agents used in carbonated beverages, and the like. The components may be used independently or in combination.
나아가 본 발명은 치매의 예방 및 개선 또는 기억력 증진 효과를 나타내는 뽕나무 열매 추출물 및 식품학적으로 허용 가능한 식품보조 첨가제를 포함하는 건강기능식품을 제공할 수 있다. Furthermore, the present invention can provide a health functional food including a mulberry fruit extract and a food supplement acceptable food supplement additive exhibiting an effect of preventing and improving dementia or memory.
본원발명의 치매 증상의 예방 및 개선 또는 기억력 증진용 조성물을 함유하는 식품에 있어서, 상기 본 발명에 따른 조성물의 양은 전체 식품 중량의 0.001중량% 내지 90중량%로 포함할 수 있으며, 바람직하게는 0.1중량% 내지 40중량%로 포함할 수 있고, 음료의 경우, 100ml를 기준으로 0.001g 내지 5g, 바람직하게는 0.01g 내지 0.1g의 비율로 포함할 수 있으나, 건강 및 위생을 목적으로 하거나 건강 조절을 목적으로 하는 장기간 섭취의 경우에는 상기 범위 이하일 수 있으며, 유효성분은 안전성 면에서 아무런 문제가 없기 때문에 상기 범위 이상의 양으로 사용될 수 있으므로 상기 범위에 한정되는 것은 아니다.In a food containing a composition for preventing and improving symptoms of dementia or improving memory of the present invention, the amount of the composition according to the present invention may include 0.001% to 90% by weight of the total food weight, preferably 0.1 It may be included in the weight% to 40% by weight, in the case of a beverage, it may be included in a ratio of 0.001g to 5g, preferably 0.01g to 0.1g based on 100ml, for health and hygiene purposes or health control In the case of long-term intake for the purpose may be less than the above range, since the active ingredient can be used in an amount above the above range because there is no problem in terms of safety is not limited to the above range.
이하, 실시예에 의하여 본 발명을 더욱 상세히 설명하고자 한다. 단, 하기 실시예는 본 발명을 예시하는 것일 뿐, 본 발명의 내용이 하기 실시예에 한정되는 것은 아니다.
Hereinafter, the present invention will be described in more detail with reference to Examples. However, the following examples are merely to illustrate the invention, but the content of the present invention is not limited to the following examples.
<< 실시예Example 1> 1>
뽕나무 열매 추출물의 제조 Preparation of Mulberry Fruit Extract
뽕나무 열매 오디의 분말시료 20g에 10배의 물과 80% 에탄올을 각각 추출용매로 사용하여 3시간씩 3회에 걸쳐 추출과정을 수행하였다. 각 추출물은 12000rpm에서 30분 동안 원심분리한 후, 상층액만을 취하여 여과지(Whatman No.6)로 여과하였다. 그 후 물로 열수추출하여 얻어진 추출물의 여과액은 70℃에서, 에탄올 추출물의 여과액은 45℃에서 감압농축 한 다음 동결 건조하여 오디 분말 추출물을 제조하였다.In 20g of mulberry fruit mulberry powder sample, 10 times of water and 80% ethanol were used as extraction solvents, and the extraction process was performed three times for 3 hours. Each extract was centrifuged at 12000 rpm for 30 minutes, and then the supernatant was taken out and filtered with filter paper (Whatman No. 6). Thereafter, the filtrate of the extract obtained by hot water extraction with water was concentrated at 70 ° C., the filtrate of ethanol extract was concentrated under reduced pressure at 45 ° C., and freeze-dried to prepare an Audi powder extract.
<< 실시예Example 2> 2>
본 발명에 따른 뽕나무 열매 추출물의 Of mulberry fruit extract according to the present invention 아세틸콜린에스테라제Acetylcholinesterase 저해 활성 분석 Inhibitory Activity Assay
본 발명에 따른 뽕나무 열매 추출물의 아세틸콜린에스테라제의 저해 활성을 확인하기 위해 Ellman et al.(1961)의 방법을 활용하였다. 즉 140μL의 100 mM 인산나트륨(sodium phosphate) 버퍼(pH 8.0)와 다양한 농도(0.10, 0.25, 0.50, 1.00mg/ml)의 뽕나무 열매의 에탄올 추출물(MFE) 및 물 추출물(MFH) 시료를 각각 20μL 넣고, 더불어 20μL의 아세틸콜린에스테라제(0.36 U/mL)를 잘 섞은 후 15분간 상온에서 반응시킨 다음, 10μL DTNB(0.5mM) 및 10μL 아세틸콜린(0.6mM)을 첨가하여 효소 반응을 시작하였다. 아세틸콜린에스테라제의 아세틸콜린 분해정도는 412nm에서 15분간 흡광도를 모니터하며 확인하였다. 본 실험의 데이터 통계처리는 실험을 3회 반복하여 행해졌으며, 그 평균값은 평균±표준편차로 표시하였으며, 실험결과는 사스 프로그램(SAS program)을 이용하여 분석하였고, 유의성 검정은 p<0.05에서 듀칸의 범위검정(Duncan's range test)을 통해 분석하였다.The method of Ellman et al. (1961) was used to confirm the inhibitory activity of acetylcholinesterase of the mulberry fruit extract according to the present invention. 20 μL of 100 mM sodium phosphate buffer (pH 8.0) and ethanol extract (MFE) and water extract (MFH) samples of mulberry fruit at various concentrations (0.10, 0.25, 0.50, 1.00 mg / ml), respectively. In addition, 20 μL of acetylcholinesterase (0.36 U / mL) was mixed well, followed by reaction at room temperature for 15 minutes, and then 10 μL DTNB (0.5 mM) and 10 μL acetylcholine (0.6 mM) were added to start the enzyme reaction. . The degree of acetylcholine degradation of acetylcholine esterase was confirmed by monitoring the absorbance at 412 nm for 15 minutes. The statistical data of this experiment was repeated three times, and the average value was expressed as mean ± standard deviation, and the experimental results were analyzed using the SAR program, and the significance test was Ducan at p <0.05. The analysis was performed using Duncan's range test.
뽕나무 열매에서 물과 에탄올을 추출용매로 하여 추출한 두 추출물을 시료 용액으로 사용하여 아세틸콜린에스테라제의 억제정도를 확인한 결과, 도 1에서와 같이 두 추출물에서 모두 농도 의존적으로 높은 아세틸콜린에스테라제의 억제효과를 보이는 것을 확인할 수 있었다. 또한 물 추출물과 에탄올 추출물은 서로 유사한 억제 활성을 보였으며 크게 차이가 있지 않아 두 추출물(MFE,MFH) 모두 1.00mg/ml 농도에서 아세틸콜린에스테라제의 활성을 70% 넘게 억제함을 알 수 있었다.As a result of confirming the inhibition of acetylcholinesterase using two extracts extracted from water and ethanol as an extract solvent from the mulberry fruit, both extracts showed high concentration-dependent acetylcholinesterase as shown in FIG. It was confirmed that the inhibitory effect of. In addition, the water extract and the ethanol extract showed similar inhibitory activities, and there was no significant difference. Both extracts (MFE and MFH) inhibited the acetylcholinesterase activity by more than 70% at the concentration of 1.00 mg / ml. .
<< 실시예Example 3> 3>
본 발명에 따른 뽕나무 열매 추출물의 자유 Freedom of mulberry fruit extract according to the present invention 라디칼Radical 소거능력 및 지질과산화 억제능력 분석 Analysis of scavenging ability and lipid peroxidation
<3-1> 자유 <3-1> freedom 라디칼Radical 소거능력 분석 Elimination ability analysis
뽕나무 열매 추출물의 자유 라디칼 소거 활성은 당업계에서 널리 사용되고 있는 DPPH 라디칼 소거 활성 모델을 이용하여 Heo 등 (2005)이 기술한 방법을 약간 변형하여 확인하였다. 우선 뽕나무 열매의 에탄올 추출물(MFE) 및 물 추출물(MFH) 시료를 다양한 농도(0.05, 0.125, 0.25, 0.5mg/ml)로 제조한 다음, 각각 시료 0.1mL와 실험 직전 1.5× 10-4M로 제조한 DPPH 용액 0.1mL을 96-웰(well) 플레이트(plate)에 첨가하여 잘 섞은 후 실온에서 30분간 반응 시킨 후 UV 분광광도계를 이용하여 517nm에서 흡광도를 측정하였다. 대조군은 시료 대신 메탄올을 넣었고, 본 실험의 데이터 통계처리는 실험을 3회 반복하여 행해졌으며, 그 평균값은 평균± 표준편차로 표시하였고, 실험결과는 사스 프로그램(SAS program)을 이용하여 분석하였으며, 유의성 검정은 p<0.05에서 듀칸의 범위검정(Duncan's range test)을 통해 분석하였다. 본 분석의 DPPH 라디칼 소거 활성은 다음과 같은 공식에 의해 계산하였다.The free radical scavenging activity of the mulberry fruit extract was confirmed by slightly modifying the method described by Heo et al. (2005) using a DPPH radical scavenging activity model widely used in the art. First, ethanol extract (MFE) and water extract (MFH) samples of mulberry fruit were prepared at various concentrations (0.05, 0.125, 0.25, 0.5 mg / ml), and then 0.1 mL of sample and 1.5 × 10 -4 M immediately before the experiment, respectively. 0.1 mL of the prepared DPPH solution was added to a 96-well plate, mixed well, and reacted at room temperature for 30 minutes, and then absorbance was measured at 517 nm using a UV spectrophotometer. In the control group, methanol was added instead of the sample, and the statistical data of the experiment was repeated three times, and the average value was expressed as the mean ± standard deviation, and the experimental results were analyzed using the SAR program. Significance test was analyzed by Ducan's range test at p <0.05. DPPH radical scavenging activity of this assay was calculated by the following formula.
DPPH 라디칼 소거 활성 (%) = [(Abs.control-Abs.sample/Abs.control)] × 100DPPH radical scavenging activity (%) = [(Abs. Control- Abs. Sample / Abs. Control )] × 100
Abs.control : Control의 흡광도Abs. control : absorbance of the control
Abs.sample : Sample의 흡광도Abs. sample : absorbance of the sample
그 결과, 본 발명에 따른 뽕나무 열매의 에탄올 추출물(MFE) 및 물 추출물(MFH) 모두에서 높은 DPPH 소거 활성이 나타났고 그 활성은 농도 의존적으로 증가함을 확인할 수 있었다. 이는 도 2에 나타내었다. DPPH 소거 활성은 에탄올 추출물(MFE)이 물 추출물(MFE) 보다 조금 높게 나타났는데 이러한 이유는 에탄올을 이용하여 추출물을 제조할 때 극성 물질 뿐만 아니라 비극성 물질의 항산화제도 같이 추출되기 때문인 것으로 판단된다.
As a result, high ethanol extract (MFE) and water extract (MFH) of the mulberry fruit according to the present invention showed a high DPPH scavenging activity and the activity was increased in a concentration-dependent manner. This is shown in FIG. DPPH scavenging activity was slightly higher than ethanol extract (MFE) than water extract (MFE), which is believed to be due to the extraction of antioxidants of non-polar substances as well as polar substances.
<3-2> <3-2> 세포내Intracellular 지질과산화 억제능력 분석 Lipid Peroxidation Inhibition Capacity Analysis
세포 내 지질과산화 정도의 측정은 형광물질인 DPPP를 이용하여 측정하였다 (Takahashi et al., 2001). 쥐(mouse)의 RAW264.7 세포를 배양 접시에 키운 후 PBS로 세 번 씻은 후 13μM DPPP를 처리한 다음 37℃에서 30분간 배양한다. 그런 다음 PBS로 다시 세 번 씻고, 96 웰(well)에 세포를 옮긴 후 세포가 웰(well)에 부착하면 뽕나무 열매의 에탄올 추출물(MFE) 및 물 추출물(MFH) 시료를 다양한 농도(50, 100, 200, 300μg/ml)로 각각 처리하여 1시간 동안 배양한 후 3mM AAPH를 첨가하여 6시간 후에 DPPP 옥사이드 형광(oxide flrorescence) 변화를 λex=361nm, λem=380 nm에서 형광 분석기로 측정하였다. 본 실험의 데이터의 통계처리는 실험을 3회 반복하여 행해졌고, 그 평균값을 평균± 표준편차로 표시하였으며, 실험결과는 사스 프로그램(SAS program)을 이용하여 분석하였고, 유의성 검정은 p<0.05에서 듀칸의 범위검정(Duncan's range test)을 통해 분석하였다.Intracellular lipid peroxidation was measured using the fluorescent substance DPPP (Takahashi et al., 2001). Mouse RAW264.7 cells were grown in a culture dish, washed three times with PBS, treated with 13 μM DPPP, and incubated at 37 ° C. for 30 minutes. Then wash again with PBS three times, transfer the cells to 96 wells (cells) attached to the wells (well), mulberry fruit ethanol extract (MFE) and water extract (MFH) samples of various concentrations (50, 100) , 200, 300μg / ml) and incubated for 1 hour, after which 3 mM AAPH was added, and after 6 hours, DPPP oxide fluorescence change was measured by a fluorescence analyzer at λex = 361nm and λem = 380 nm. Statistical processing of the data in this experiment was performed three times the experiment, the average value was expressed as the mean ± standard deviation, the experimental results were analyzed using the SAR program, the significance test at p <0.05 Analyzes were performed using Ducan's range test.
그 결과, 도 3에서 보는 바와 같이 강력한 알킬 라디칼 제공자인 AAPH를 처리한 후 RAW264.7 세포의 대조군(control group)에서는 DPPP 옥사이드의 형광도(fluorescence intensity)가 증가한 것으로 보아 AAPH에 의해서 지질과산화(lipid peroxidation)가 일어났음을 알 수 있었다. 그러나 뽕나무 열매 추출물을 처리한 군에서는 모두 지질과산화 현상이 억제되어 DPPP 옥사이드의 형광도(fluorescence intensity)가 농도 의존적으로 감소함을 알 수 있었고, 에탄올 추출물(MFE)의 지질과산화 억제능이 물 추출물(MFH) 보다 우수한 것으로 나타났다. As a result, the fluorescence intensity of DPPP oxide increased in the control group of RAW264.7 cells after treatment with AAPH, a strong alkyl radical provider, as shown in FIG. 3. peroxidation). However, in the group treated with the mulberry fruit extract, lipid peroxidation was suppressed, and the fluorescence intensity of DPPP oxide was reduced depending on the concentration. The ethanol extract (MFE) inhibited the lipid peroxidation of water extract (MFH). Was better than).
따라서 본 발명에 따른 뽕나무 열매 추출물은 아세틸콜린에스테라제를 효과적으로 억제하여 치매 질환의 예방 또는 치료제로서 유용하게 사용될 수 있을 뿐 만 아니라, 세포내 지질과산화로 인해 유발되는 신경세포의 손상으로부터 신경세포를 보호하는 기능 또한 부수적으로 기대할 수 있어 더더욱 우수한 치매 증상의 치료 또는 개선 효과를 나타낼 수 있음을 확인할 수 있었다.
Therefore, the mulberry fruit extract according to the present invention can effectively inhibit acetylcholinesterase and be useful as a prophylactic or therapeutic agent for dementia disease, as well as to prevent nerve cells from damage of nerve cells caused by intracellular lipid peroxidation. The protective function could also be expected as an incidental result, indicating that the treatment could improve or improve the symptoms of dementia.
이제까지 본 발명에 대하여 그 바람직한 실시예들을 중심으로 살펴보았다. 본 발명이 속하는 기술 분야에서 통상의 지식을 가진 자는 본 발명이 본 발명의 본질적인 특성에서 벗어나지 않는 범위에서 변형된 형태로 구현될 수 있음을 이해할 수 있을 것이다. 그러므로 개시된 실시예들은 한정적인 관점이 아니라 설명적인 관점에서 고려되어야 한다. 본 발명의 범위는 전술한 설명이 아니라 특허청구범위에 나타나 있으며, 그와 동등한 범위 내에 있는 모든 차이점은 본 발명에 포함된 것으로 해석되어야 할 것이다.
So far I looked at the center of the preferred embodiment for the present invention. Those skilled in the art will appreciate that the present invention can be implemented in a modified form without departing from the essential features of the present invention. Therefore, the disclosed embodiments should be considered in an illustrative rather than a restrictive sense. The scope of the present invention is shown in the claims rather than the foregoing description, and all differences within the scope will be construed as being included in the present invention.
Claims (5)
상기 뽕나무 열매 추출물은 물, 유기용매 또는 물과 유기용매의 혼합용매를 이용해 추출하여 얻어지는 것을 특징으로 하는 아세틸콜린에스테라제 억제용 조성물.The method of claim 1,
The mulberry fruit extract is a composition for inhibiting acetylcholinesterase, characterized in that the extract is obtained by using water, an organic solvent or a mixed solvent of water and an organic solvent.
상기 유기용매는 메탄올, 에탄올, 프로판올, 이소프로판올, 부탄올, 아세톤, 에테르, 벤젠, 클로로포름, 에틸아세테이트, 메틸렌클로라이드, 헥산 및 시클로헥산으로 이루어진 군중에서 선택되는 것임을 특징으로 아세틸콜린에스테라제 억제용 조성물. The method of claim 2,
The organic solvent is acetylcholinesterase inhibitory composition, characterized in that selected from the group consisting of methanol, ethanol, propanol, isopropanol, butanol, acetone, ether, benzene, chloroform, ethyl acetate, methylene chloride, hexane and cyclohexane.
A dietary supplement comprising a mulberry fruit extract and a food-acceptable food supplement additive that has an effect of preventing and improving dementia or improving memory.
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| KR1020100039443A KR20110119983A (en) | 2010-04-28 | 2010-04-28 | Composition comprising extracts of mulberry fruits for inhibiting activity of acetylcholinesterase |
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| KR1020100039443A KR20110119983A (en) | 2010-04-28 | 2010-04-28 | Composition comprising extracts of mulberry fruits for inhibiting activity of acetylcholinesterase |
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| KR1020120076197A Division KR101251866B1 (en) | 2012-07-12 | 2012-07-12 | Composition comprising extracts of Mulberry fruits for inhibiting activity of acetylcholinesterase |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2018500319A (en) * | 2014-12-19 | 2018-01-11 | ドン−ア エスティ カンパニー リミテッド | Composition for prevention, amelioration or treatment of degenerative neurological diseases, comprising a mixed extract of mulberry coconut and bukkyou skin |
| US10864238B2 (en) | 2014-12-19 | 2020-12-15 | Neurobo Pharmaceuticals, Inc. | Composition containing Poria cocos peel extract for treating neurodegenerative disorders |
-
2010
- 2010-04-28 KR KR1020100039443A patent/KR20110119983A/en not_active Application Discontinuation
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2018500319A (en) * | 2014-12-19 | 2018-01-11 | ドン−ア エスティ カンパニー リミテッド | Composition for prevention, amelioration or treatment of degenerative neurological diseases, comprising a mixed extract of mulberry coconut and bukkyou skin |
| US10588927B2 (en) | 2014-12-19 | 2020-03-17 | Neurobo Pharmaceuticals, Inc. | Composition containing mixed extract of mulberry and Poria cocos peel |
| US10864238B2 (en) | 2014-12-19 | 2020-12-15 | Neurobo Pharmaceuticals, Inc. | Composition containing Poria cocos peel extract for treating neurodegenerative disorders |
| US10946053B2 (en) | 2014-12-19 | 2021-03-16 | Neurobo Pharmaceuticals, Inc. | Composition containing mixed extract of mulberry and Poria cocos bark for preventing, improving or treating neurodegenerative disorders |
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