KR102138251B1 - A composition for preventing or treating cognitive dysfunction comprising Bauhinia extract - Google Patents
A composition for preventing or treating cognitive dysfunction comprising Bauhinia extract Download PDFInfo
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- KR102138251B1 KR102138251B1 KR1020160120791A KR20160120791A KR102138251B1 KR 102138251 B1 KR102138251 B1 KR 102138251B1 KR 1020160120791 A KR1020160120791 A KR 1020160120791A KR 20160120791 A KR20160120791 A KR 20160120791A KR 102138251 B1 KR102138251 B1 KR 102138251B1
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- extract
- bauhinia
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- cognitive dysfunction
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Abstract
본 발명은 바우히니아 추출물 또는 이의 분획물을 포함하는 인지기능 장애의 예방 또는 치료용 조성물, 상기 조성물을 이용한 인지기능 장애의 예방 또는 치료 방법, 바우히니아 추출물 또는 이의 분획물을 포함하는 인지기능 장애의 예방 또는 개선용 건강기능식품 조성물에 관한 것이다.
본 발명의 바우히니아 추출물을 포함하는 조성물은 인지기능 장애의 주요 생리지표인 아세틸콜린 분해효소 활성과 아밀로이드 베타 응집에 대한 높은 저해 효능, 항산화 효능 및 외부 자극에 대한 유의한 세포 보호 효과를 보이므로, 인지기능 장애의 예방, 개선 또는 치료를 위한 의약품 또는 건강기능식품에 적용하여 이용할 수 있다.The present invention is a composition for preventing or treating a cognitive dysfunction comprising the Bauhinia extract or a fraction thereof, a method for preventing or treating a cognitive dysfunction using the composition, a cognitive dysfunction comprising the Bauhinia extract or a fraction thereof It relates to a health functional food composition for prevention or improvement.
Since the composition comprising the Bauhinia extract of the present invention shows acetylcholine degrading enzyme activity, which is a major physiological index of cognitive dysfunction, and high inhibitory effect on amyloid beta aggregation, antioxidant effect, and significant cell protection against external stimulation. , It can be applied to medicines or health functional foods for prevention, improvement or treatment of cognitive dysfunction.
Description
본 발명은 바우히니아 추출물을 포함하는 인지기능 장애의 예방 또는 치료용 조성물에 관한 것으로, 구체적으로 바우히니아 추출물 또는 이의 분획물을 포함하는 인지기능 장애의 예방 또는 치료용 약학 조성물, 상기 약학 조성물을 투여하는 단계를 포함하는 인지기능 장애의 예방 또는 치료 방법, 및 상기 추출물 또는 이의 분획물을 포함하는 건강기능식품 조성물에 관한 것이다.The present invention relates to a composition for the prevention or treatment of cognitive dysfunction comprising a Bauhinia extract, specifically, a pharmaceutical composition for the prevention or treatment of a cognitive dysfunction comprising the Bauhinia extract or a fraction thereof, the pharmaceutical composition A method for preventing or treating a cognitive dysfunction comprising the step of administering, and a health functional food composition comprising the extract or a fraction thereof.
인지기능의 능력을 상실하는 인지기능 장애는 치매(dementia)와 경도인지장애(mild cognitive impairment)로 나눌 수 있다. 경도인지장애는 주관적인 기억력장애를 호소하거나 객관적인 검사 상 이상이 발견되지만, 일상생활을 영위하는데 지장이 없고 정신기능도 정상적으로 유지되어 결코 치매라고는 할 수 없는 상태이다. 경도인지장애의 발생 이전에 이미 뇌에서는 신경세포를 사멸시키는 과정이 진행되고 있지만, 이 시기에는 아직 아무런 증상이 없고 정상 노화로 인한 기억력 장애와 구별하기 어렵다. 경도인지장애는 치매보다 흔하게 나타나며, 60세 노인의 15∼30%가 여기에 해당할 수 있고, 나이가 증가할수록 증가한다. 경도인지장애의 상태는 현재 정상과 알츠하이머병의 중간 정도의 인지기능의 장애를 의미하고, 매년 15% 정도가 치매의 증상으로 발전하게 된다. 치매는 2050년에 세계 치매 환자가 2013년 대비 3.1배인 1억명을 넘어서리란 전망이며, 한국은 65세 이상 인구가 20%를 넘는 초고령화로 인해 세계에서 치매 환자가 가장 빨리 늘어나는 국가가 될 것으로 보임으로써 중대한 사회적 관심사로 떠오르고 있다.Cognitive dysfunction, which is a loss of cognitive function, can be divided into dementia and mild cognitive impairment. Mild cognitive impairment complains of subjective memory impairment or abnormality is found on objective tests, but it is a condition that can never be called dementia because it does not interfere with daily life and maintains normal mental functions. Prior to the occurrence of mild cognitive impairment, the brain is already in the process of killing nerve cells, but at this time there are no symptoms and it is difficult to distinguish from memory impairment due to normal aging. Mild cognitive impairment is more common than dementia, and may range from 15 to 30% of 60-year-olds, and increases with age. The condition of mild cognitive impairment means a disorder of cognitive function between normal and Alzheimer's disease, and about 15% develops symptoms of dementia every year. Dementia is expected to exceed 100 million people with dementia in the world by 3.1 times compared to 2013 in 2050, and Korea is expected to be the fastest growing dementia patient in the world due to the aging population over 20% over the age of 65. As a result, it has emerged as a major social concern.
치매는, 특정 질환명이 아니고 인지 기능 저하의 특정한 상태를 일컫는 말로 원인 질환은 약 100여 가지가 존재한다. 이 중, 치매의 주요 원인 질환으로 퇴행성 뇌질환인 알츠하이머는 치매의 50%이상을 차지하며, 알츠하이머로 인한 비가역적인 행동과 인성의 변화, 사고능력의 저하와 같은 증상의 정확한 원인과 치료법이 밝혀지지는 않았지만, 신경전달체계인 콜린성 신경계의 기능저하와 염증반응에 의한 베타-아밀로이드(β-amyloid) 단백질 축적 및 산화성 스트레스 등이 보고되어 (Science, 262, 689, 1993), 인지기능의 손상과 밀접한 관계가 있다는 것이 밝혀졌다. 이에 따라, 뇌에서 아세틸콜린의 분해효소인 acetylcholinesterase(AChE)의 활성을 억제하여 아세틸콜린의 농도를 유지하며, 치매 초기의 베타-아밀로이드 응집을 억제하려는 노력이 최근까지 활발하게 진행되고 있다. 또한, 항산화 활성을 측정하기 위해 전자전달계를 조절(DPPH, 1,1-diphenyl-2-picrylhydrazyl 라디칼 소거능; ABTS, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonicacid 소거능)하는 방법 및 세포사멸의 원인이 될 수 있는 활성산소종(ROS)에 대한 신경 세포 보호 효과를 보일 수 있는 방법을 모색하고 있다.Dementia is not a specific disease name, but refers to a specific condition of cognitive decline, and there are about 100 causes of the disease. Of these, Alzheimer's, a degenerative brain disease that is a major cause of dementia, accounts for more than 50% of dementia, and the exact cause and treatment of symptoms such as irreversible behavior and personality changes caused by Alzheimer's, and decreased thinking ability are not identified. Although it has not been reported, beta-amyloid protein accumulation and oxidative stress due to hypotonic inflammatory reactions and inflammatory reactions have been reported (Science, 262, 689, 1993), closely related to impaired cognitive function. It turns out that there is a relationship. Accordingly, efforts to suppress the activity of acetylcholinesterase (AChE), an enzyme that breaks down acetylcholine in the brain, maintain the concentration of acetylcholine, and efforts to suppress beta-amyloid aggregation in the early stages of dementia have been actively conducted until recently. In addition, to measure the antioxidant activity, the method of controlling the electron transport system (DPPH, 1,1-diphenyl-2-picrylhydrazyl radical scavenging ability; ABTS, 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulphonicacid scavenging ability) and We are looking for ways to show neuroprotective effects against reactive oxygen species (ROS), which can cause apoptosis.
그러나, 현재까지 치매의 원인 및 그 치료법에 대한 광범위하고 다양한 연구가 진행되었지만, 원인규명이 미비하고 효과적인 치료법의 개발 또한 미진하다. 현재 사용되는 치료제는 초기에 발견한다면 이라는 전제하에 질병의 진행을 지연시키고 증상을 완화시키는 등 제한적인 약효에 불과하고, 또한, 신경세포에 대한 보호 효과는 신경세포의 사멸이 진행될수록 약물의 효과가 저하되며, 중증 치매의 경우 그 효과는 더욱 미약하다.However, although a wide variety of studies have been conducted on the causes of dementia and their treatments, development of effective treatments with insufficient cause identification is also insufficient. The currently used treatments are only limited medicinal effects such as delaying disease progression and alleviating symptoms under the premise that if found in the early stages, the protective effect on nerve cells is also more effective as the death of nerve cells progresses. It decreases, and in severe dementia, the effect is weaker.
한편, 바우히니아는 콩과(科) Bauhinia 속(屬)의 각종 교목·관목·덩굴 식물의 총칭으로 열대와 아열대 지방에 200종 정도가 있으며, 높이 5~8m까지 자라고, 잎은 좌우 대칭인 바우히니아 속만의 특징을 가지고 있다. 이러한 다양한 바우히니아 속의 추출물이 포함된 조성물은 골다공증 예방, 항염증제, 항노화제, 피부외용제 치료에 효과적임이 보고된 바 있다.Meanwhile, Bauhinia is a generic term for various trees, shrubs, and vines of the genus Bauhinia. There are about 200 species in tropical and subtropical regions. It grows up to 5-8m in height and leaves are symmetrical. It has the characteristics of the Bauhinia genus. These various Bauhinia genus extract-containing compositions have been reported to be effective in preventing osteoporosis, anti-inflammatory agents, anti-aging agents, and external skin preparations.
이 외에도, 여러 바우히니아로부터 분리된 성분이 항산화 및 혈당강하 작용을 가짐으로써 경구혈당 강하체로써 유용함이 공지된 바 있지만(국제공개특허 WO2003-011311), 상기 바우히니아 추출물의 인지기능 장애에 대한 효과는 밝혀진 바 없다.In addition, although it has been known that components separated from various Bauhinias have anti-oxidation and hypoglycemic properties, they are useful as oral hypoglycemic bodies (International Publication WO2003-011311), however, in the cognitive impairment of the Bauhinia extract. No effect has been found.
이러한 배경 하에서, 본 발명자들은 인지기능 장애의 예방, 개선 또는 치료 효과를 나타내면서 부작용이 적고 인체에 무해한 천연물을 찾고자 예의 노력한 결과, 바우히니아 추출물이 아세틸콜린 분해효소 활성 억제, 아밀로이드 베타 응집 억제, 항산화 효과 및 신경세포 보호 효과가 있음을 확인하고, 이를 약제 또는 건강기능식품에 적용할 수 있음을 확인함으로써, 본 발명을 완성하였다.Under this background, the present inventors tried to find a natural product that has little side effects and is harmless to the human body while exhibiting the prevention, improvement or treatment effect of cognitive dysfunction, and the Bauhinia extract inhibits acetylcholine degrading enzyme activity, inhibits amyloid beta aggregation, and antioxidant The present invention was completed by confirming that it has an effect and a protective effect on neurons, and confirming that it can be applied to a drug or a health functional food.
본 발명의 목적은 바우히니아 추출물 또는 이의 분획물을 포함하는 인지장애 예방 또는 치료용 약학 조성물을 제공하는 것이다.An object of the present invention is to provide a pharmaceutical composition for preventing or treating cognitive impairment comprising a Bauhinia extract or a fraction thereof.
본 발명의 다른 목적은 상기 조성물을 개체에 투여하는 것을 포함하는 인지기능 장애 예방 또는 치료 방법을 제공하는 것이다.Another object of the present invention is to provide a method for preventing or treating cognitive dysfunction, comprising administering the composition to an individual.
본 발명의 또 다른 목적은 바우히니아 추출물 또는 이의 분획물을 포함하는 인지장애 예방 또는 개선용 건강기능식품 조성물을 제공하는 것이다.Another object of the present invention is to provide a health functional food composition for preventing or improving cognitive impairment comprising a Bauhinia extract or a fraction thereof.
상기 목적을 달성하기 위한 하나의 양태로서, 본 발명은 바우히니아 추출물 또는 이의 분획물을 포함하는 인지장애 예방 또는 치료용 약학 조성물을 제공한다.As one aspect for achieving the above object, the present invention provides a pharmaceutical composition for preventing or treating cognitive disorders comprising a Bauhinia extract or a fraction thereof.
본 발명의 조성물의 유효성분인 바우히니아 추출물은 아세틸콜린 분해효소 활성 및 아밀로이드 베타 응집 억제 활성이 뛰어나고, ABTS 양이온 라디칼 및 DPPH 자유 라디칼의 소거능을 가지는 뛰어난 항산화 효능을 가진다. 또한, H2O2 에 의해 유도된 신경 해마 세포 손상에 대한 높은 보호 효과를 보이므로, 상기 추출물은 인지기능 장애의 예방, 치료에 사용될 수 있다.The Bauhinia extract, an active ingredient of the composition of the present invention, has excellent acetylcholinesease activity and amyloid beta aggregation inhibitory activity, and has excellent antioxidant efficacy with scavenging ability of ABTS cationic radical and DPPH free radical. In addition, H 2 O 2 Because it shows a high protective effect against nerve hippocampal cell damage induced by, the extract can be used for the prevention and treatment of cognitive impairment.
본 발명의 용어, “바우히니아”란, 콩과의 덩굴식물로서, 한국, 말레이시아, 보르네오, 베트남 등에 서식한다. 예를 들어, 상기 바우히니아는 B. coccinea, B. blakeana를 포함할 수 있으나, 이에 제한되는 것은 아니다. 상기 바우히니아의 인지기능 장애에 대한 효과는 지금까지 전혀 알려져 있지 않았고, 본 발명자에 의하여 최초로 규명되었다. 본 발명에서 바우히니아는 상업적으로 판매되는 것을 구입하거나 재배 또는 채취하여 사용할 수 있다. The term "bauhinia" of the present invention is a vine plant of the legume, and inhabits Korea, Malaysia, Borneo, Vietnam, and the like. For example, the Bauhinia may include B. coccinea, B. blakeana, but is not limited thereto. The effect of Bauhinia on cognitive dysfunction has never been known, and was first identified by the inventors. In the present invention, Bauhinia can be used by purchasing or cultivating or collecting commercially available ones.
본 발명의 용어, “추출물”이란, 바우히니아를 추출 처리하여 얻어지는 추출액, 상기 추출액의 희석액이나 농축액, 상기 추출액을 건조하여 얻어지는 건조물, 상기 추출액의 조정제물이나 정제물, 또는 이들의 혼합물 등, 추출액 자체 및 추출액을 이용하여 형성 가능한 모든 제형의 추출물을 포함한다. 본 발명의 상기 추출물 또는 분획물은 구체적으로 추출 후 건조 분말 형태로 제조되어 사용될 수 있다.The term “extract” of the present invention means an extract obtained by extracting Bauhinia, a dilution or concentrate of the extract, a dried product obtained by drying the extract, a crude product or a purified product of the extract, or a mixture thereof, It includes the extract itself and extracts of all formulations that can be formed using the extract. The extract or fraction of the present invention may be specifically prepared and used in dry powder form after extraction.
본 발명의 상기 바우히니아 추출물에 있어서, 상기 바우히니아를 추출하는 방법은 특별히 제한되지 아니하며, 당해 기술 분야에서 통상적으로 사용하는 방법에 따라 추출할 수 있다. 상기 추출 용매의 비제한적인 예로는 물, 알코올, 헥산 또는 이들의 혼합 용매 등을 들 수 있으며, 알코올을 용매로 사용하는 경우에는 일 예로서 C1 내지 C4의 알코올을 사용할 수 있다. 다른 예로서 본 발명의 바우히니아 추출물은 구체적으로는 에탄올 추출물일 수 있다.In the Bauhinia extract of the present invention, the method for extracting the Bauhinia is not particularly limited, and can be extracted according to a method commonly used in the art. Non-limiting examples of the extraction solvent include water, alcohol, hexane, or a mixed solvent thereof, and when using alcohol as a solvent, C1 to C4 alcohol may be used as an example. As another example, the Bauhinia extract of the present invention may be specifically an ethanol extract.
또한, 상기 추출물은 추출 또는 분획 과정을 수행한 이후, 감압 여과 과정을 수행하거나 추가로 농축 및/또는 동결건조를 수행하여 농축하거나 용매를 제거할 수 있으며, 상기 수득한 바우히니아 추출물은 사용 시까지 급속 냉동 냉장고에 보관할 수 있다.In addition, after performing the extraction or fractionation process, the extract can be concentrated or removed by performing a vacuum filtration process or further performing concentration and/or lyophilization, and the obtained Bauhinia extract is used until It can be stored in a deep freezer.
본 발명의 상기 바우히니아 추출물은 바우히니아 소지 추출물일 수 있다.The Bauhinia extract of the present invention may be a Bauhinia possession extract.
본 발명의 용어, “소지(twig)”란, 식물의 줄기에서 간(幹) 및 대지(大枝)를 제외한 어린 나뭇가지를 가르킨다.The term "twig" in the present invention refers to a young twig excluding the liver and earth from the stem of a plant.
본 발명의 용어, “분획물”이란, 여러 다양한 구성 성분들을 포함하는 혼합물로부터 특정 성분 또는 특정 성분 그룹을 분리하기 위하여 분획을 수행하여 얻어진 결과물을 의미한다.The term "fraction" of the present invention means a result obtained by performing a fraction to separate a specific component or a specific component group from a mixture containing various various components.
본 발명에서 상기 분획물을 얻는 분획 방법은 특별히 제한되지 아니하며, 당해 기술 분야에서 통상적으로 사용하는 방법에 따라 수행될 수 있다. 상기 분획 방법의 비제한적인 예로는, 바우히니아를 추출하여 얻은 추출물에 소정의 용매를 처리하여 상기 추출물로부터 분획물을 얻는 방법을 들 수 있다.The fractionation method for obtaining the fraction in the present invention is not particularly limited, and may be performed according to a method commonly used in the art. Non-limiting examples of the fractionation method include a method of obtaining a fraction from the extract by treating a predetermined solvent with an extract obtained by extracting Bauhinia.
본 발명에서 상기 분획물을 얻는 데에 사용되는 분획 용매의 종류는 특별히 제한되지 아니하며, 당해 기술 분야에서 공지된 임의의 용매를 사용할 수 있다. 상기 분획 용매의 비제한적인 예로는 물, 알코올 등의 극성 용매; 헥산(Hexane), 에틸아세테이트(Ethyl acetate), 클로로포름(Chloroform), 디클로로메탄(Dichloromethane) 등의 비극성 용매 등을 들 수 있다. 이들은 단독으로 사용되거나 2 종 이상 혼합하여 사용될 수 있다. 상기 분획 용매 중 알코올을 사용하는 경우에는 구체적으로 C1 내지 C4의 알코올을 사용할 수 있다.In the present invention, the type of fractional solvent used to obtain the fraction is not particularly limited, and any solvent known in the art may be used. Non-limiting examples of the fractional solvent include polar solvents such as water and alcohol; And non-polar solvents such as hexane, ethyl acetate, chloroform, and dichloromethane. These may be used alone or in combination of two or more. When using an alcohol in the fractional solvent, specifically, C1 to C4 alcohol may be used.
본 발명의 용어, “인지기능”이란, 주의력, 지각력, 기억력, 언어능력, 집행능력등의 다양한 지적 능력으로서, 본 발명의 목적상 인지기능 장애는 상기와 같은 인지기능이 저하되어 생기는 상태, 그에 따른 질환, 그를 증상으로 하는 모든 질환을 포함할 수 있는 개념으로써, 구체적으로 뇌 신경세포의 손상으로 발생하는 장애를 의미할 수 있다. 예를 들어, 상기 인지기능 장애는 건망증, 알츠하이머병, 치매, 파킨슨병, 피크병, 및 헌팅톤병으로 이루어지는 군에서 선택되는 퇴행성 뇌질환을 의미할 수 있다.The term "cognitive function" of the present invention is a variety of intellectual abilities such as attention, perception, memory, language ability, and executive ability. For the purposes of the present invention, cognitive dysfunction occurs when the cognitive function as described above is lowered. As a concept that can include all diseases that cause symptoms and diseases according to it, it may specifically mean a disorder caused by damage to brain neurons. For example, the cognitive dysfunction may refer to degenerative brain disease selected from the group consisting of forgetfulness, Alzheimer's disease, dementia, Parkinson's disease, Peak disease, and Huntington's disease.
본 발명의 용어, “치매(dementia)”란, 후천적으로 기억, 언어, 판단력 등의 여러 영역의 인지기능이 감소하여 일상생활을 제대로 수행하지 못하는 증후군을 의미하며, 다양한 원인에 의하여 뇌기능이 손상되면서 이전에 비해 인지 기능이 지속적으로 전반적으로 저하되어 일상생활에 상당한 지장이 나타날 수 있다. 상기 치매는 원인 질환으로 세분화할 경우 수십 가지에 이르나, 그 중에서도 알츠하이머병에 의한 원인이 가장 많으며 50%를 넘는다. 이 밖에도, 루이체 치매, 전측두엽 퇴행, 파킨슨 병 등의 퇴행성 뇌질환 등 다양한 원인 질환에 의해 치매가 발생할 수 있다. 따라서 본 발명에서 치매는 노인성 치매, 알츠하이머병, 혈관성 치매, 루이체 치매, 전측두엽 치매, 파킨슨병 치매, 헌팅턴병 치매, 정상압 뇌수두증에 의한 치매, 또는 두부 외상으로 인한 치매를 의미할 수 있다. The term “dementia” in the present invention refers to a syndrome in which cognitive functions in various areas such as memory, language, and judgment are reduced, and thus, cannot properly perform daily life, and brain function is impaired by various causes. As a result, the cognitive function continuously decreases overall compared to the previous one, which may cause significant obstacles in daily life. The dementia is divided into dozens of cases when it is subdivided into causative diseases, but most of them are caused by Alzheimer's disease and exceed 50%. In addition, dementia may occur due to various causative diseases such as degenerative brain diseases such as Lewy body dementia, anterior temporal lobe degeneration, and Parkinson's disease. Therefore, in the present invention, dementia may mean senile dementia, Alzheimer's disease, vascular dementia, Lewy body dementia, frontotemporal dementia, Parkinson's disease dementia, Huntington's disease dementia, dementia due to normal pressure hydrocephalus, or dementia due to head trauma.
본 발명의 구체적인 일 실시예에서는, 본 발명의 바우히니아 추출물을 처리한 결과, 아세틸콜린 분해효소 저해 및 아밀로이드 베타 응집을 억제하는 높은 활성을 확인하였고(도 1 및 도 2); 높은 항산화 활성을 가짐을 확인하였다(도 3). 또한, 신경 세포 손상이 유도된 HT22 세포를 이용하여 신경세포의 생존율이 향상됨을 확인하였다(도 4). 이는, 상기 바우히니아 추출물은 인지장애에 대한 예방, 치료 또는 개선에 유용하게 이용될 수 있음을 시사하는 것이다.In a specific embodiment of the present invention, as a result of treating the Bauhinia extract of the present invention, it was confirmed that high activity of inhibiting acetylcholine degrading enzyme inhibition and amyloid beta aggregation (FIGS. 1 and 2); It was confirmed to have a high antioxidant activity (Fig. 3). In addition, it was confirmed that the survival rate of neurons is improved by using HT22 cells inducing neuronal damage (FIG. 4 ). This suggests that the Bauhinia extract can be useful for prevention, treatment, or improvement of cognitive impairment.
본 발명의 용어, “예방”이란, 본 발명의 바우히니아 추출물 또는 이의 분획물을 포함하는 약학 조성물의 투여에 의해 인지기능 장애를 억제시키거나 또는 지연시키는 모든 행위를 의미한다.The term "prevention" of the present invention means all actions that inhibit or delay cognitive impairment by administration of a pharmaceutical composition comprising the Bauhinia extract or fractions thereof of the present invention.
본 발명의 용어, “치료”란, 상기 약학 조성물의 투여에 의해 인지장애가 호전되거나 이롭게 변경되는 모든 행위를 의미한다.The term “treatment” of the present invention means all actions in which cognitive impairment is improved or advantageously changed by administration of the pharmaceutical composition.
본 발명의 약학 조성물은 총 조성물의 중량 대비 바우히니아 추출물 또는 그의 분획물을 0.01 내지 100 중량%로 포함할 수 있으며, 구체적으로 1 중량% 내지 80 중량%로 포함할 수 있으나, 이에 제한되지 않는다. The pharmaceutical composition of the present invention may include a Bauhinia extract or a fraction thereof in an amount of 0.01 to 100% by weight, and specifically 1 to 80% by weight, but is not limited thereto.
본 발명에 따른 인지기능 관련 질환의 예방 또는 치료용 약학 조성물은 약학적으로 허용 가능한 담체를 추가로 포함할 수 있으며, 상기 담체와 함께 제제화되어, 식품, 의약품, 사료 첨가제 및 음용수 첨가제 등으로 제공될 수 있다. The pharmaceutical composition for the prevention or treatment of diseases related to cognitive function according to the present invention may further include a pharmaceutically acceptable carrier, and is formulated with the carrier to be provided as a food, pharmaceutical, feed additive and drinking water additive, etc. Can.
본 발명의 용어, “약학적으로 허용 가능한”이란, 상기 조성물에 노출되는 세포나 인간에게 독성이 없는 특성을 나타내는 것을 의미하며, 이때, 상기 담체는 비자연적인 담체(non-naturally occurin carrier)를 포함할 수 있다. 약학적으로 허용 가능한 담체를 포함하는 조성물은 경구 또는 비경구의 여러 가지 제형일 수 있다. 제제화할 경우에는 보통 사용하는 충진제, 증량제, 결합제, 습윤제, 붕해제, 계면활성제 등의 희석제 또는 부형제를 사용하여 조제될 수 있다. 상기 담체, 부형제 및 희석제로는 락토스, 덱스트로스, 수크로스, 솔비톨, 만니톨, 자일리톨, 에리스리톨, 말티톨, 전분, 아카시아 고무, 알지네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실리케이트, 셀룰로오스, 메틸 셀룰로오스, 미정질 셀룰로오스, 폴리비닐 피롤리돈, 생리식염수, 메틸히드록시벤조에이트, 프로필히드록시벤조에이트, 탈크, 마그네슘 스테아레이트 및 광물유, 덱스트린, 칼슘 카보네이트, 프로필렌글리콜 및 리퀴드 파라핀으로 이루어진 군에서 선택된 하나 이상일 수 있으나, 이에 한정되는 것은 아니며, 통상의 담체, 부형제 또는 희석제 모두 사용가능하다. 상기 성분들은 상기 유효성분인 바우히니아 추출물에 독립적으로 또는 조합하여 추가될 수 있다.The term of the present invention, "pharmaceutically acceptable" means that the non-toxic characteristics of cells or humans exposed to the composition, wherein the carrier is a non-naturally occurring carrier (non-naturally occurin carrier) It can contain. The composition comprising a pharmaceutically acceptable carrier may be various oral or parenteral formulations. When formulated, it may be prepared using diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrating agents, surfactants, etc., which are usually used. The carrier, excipients and diluents include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, It may be one or more selected from the group consisting of polyvinyl pyrrolidone, physiological saline, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil, dextrin, calcium carbonate, propylene glycol and liquid paraffin. It is not limited, and any conventional carrier, excipient, or diluent may be used. The components may be added to the active ingredient Bauhinia extract independently or in combination.
경구 투여를 위한 고형제제에는 정제환제, 산제, 과립제, 캡슐제 등이 포함될 수 있으며, 이러한 고형제제는 하나 이상의 화합물에 적어도 하나 이상의 부형제, 예를 들면, 전분, 탄산칼슘, 수크로스(sucrose) 또는 락토스(lactose), 젤라틴 등을 섞어 조제될 수 있다. 또한, 단순한 부형제 이외에 스테아린산 마그네슘, 탈크 등과 같은 윤활제들도 사용될 수 있다. 경구 투여를 위한 액상제제로는 현탁제, 내용액제, 유제, 시럽제 등이 해당되는데 흔히 사용되는 단순희석제인 물, 리퀴드 파라핀 이외에 여러 가지 부형제, 예를 들면 습윤제, 감미제, 방향제, 보존제 등이 포함될 수 있다. 비경구 투여를 위한 제제에는 멸균된 수용액, 비수성용제, 현탁제, 유제, 동결건조제제, 좌제가 포함될 수 있다. 비수성용제, 현탁용제로는 프로필렌 글리콜(propylene glycol), 폴리에틸렌 글리콜, 올리브 오일과 같은 식물성 기름, 에틸올레이트와 같은 주사 가능한 에스테르 등이 사용될 수 있다. 좌제의 기제로는 위텝솔(witepsol), 마크로골, 트윈(tween) 61, 카카오지, 라우린지, 글리세로젤라틴 등이 사용될 수 있다.Solid preparations for oral administration may include tablets, powders, granules, capsules, etc. These solid preparations include at least one excipient in one or more compounds, such as starch, calcium carbonate, sucrose or It can be prepared by mixing lactose, gelatin, etc. In addition, lubricants such as magnesium stearate, talc and the like may be used in addition to simple excipients. Liquid preparations for oral administration include suspending agents, intravenous solutions, emulsions, syrups, etc. In addition to water and liquid paraffin, which are commonly used as diluents, various excipients, such as wetting agents, sweeteners, fragrances, and preservatives, can be included. have. Formulations for parenteral administration may include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, and suppositories. As a non-aqueous solvent and a suspension solvent, propylene glycol, polyethylene glycol, vegetable oil such as olive oil, and injectable ester such as ethyl oleate may be used. As a base for suppositories, witepsol, macrogol, tween 61, cacao butter, laurin butter, and glycerogelatin may be used.
또한, 본 발명의 약학적 조성물은 정제, 환제, 산제, 과립제, 캡슐제, 현탁제, 내용액제, 유제, 시럽제, 멸균된 수용액, 비수성용제, 현탁제, 유제, 동결건조제제 및 좌제로 이루어진 군으로부터 선택되는 어느 하나의 제형을 가질 수 있다.In addition, the pharmaceutical composition of the present invention is a group consisting of tablets, pills, powders, granules, capsules, suspensions, intravenous solutions, emulsions, syrups, sterilized aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilizers and suppositories It may have any one formulation selected from.
본 발명의 약학 조성물은 약학적으로 유효한 양으로 투여할 수 있다. 그 투여용량에 특별한 제약은 없고, 체내 흡수도, 체중, 환자의 연령, 성별, 건강상태, 식이, 투여시간, 투여방법, 배설율 및 질환의 중증도 등에 따라 변화될 수 있다. 본 발명의 약학적 조성물은 유효량 범위를 고려하여 제조하도록 하며, 이렇게 제형화 된 단위 투여형 제제는 필요에 따라 약제의 투여를 감시하거나 관찰하는 전문가의 판단과 개인의 요구에 따라 전문화된 투약법을 사용하거나 일정 시간 간격으로 수회 투여할 수 있다. 구체적으로, 본 발명의 약학 조성물은 바우히니아 추출물의 양을 기준으로 1일 0.0001 내지 1000 mg/kg으로, 보다 구체적으로는 0.01 내지 100 mg/kg으로 투여할 수 있으며, 상기 투여는 하루에 한 번 투여할 수도 있고, 수회 나누어 투여할 수도 있다.The pharmaceutical composition of the present invention can be administered in a pharmaceutically effective amount. There is no particular restriction on the dosage, and it can be changed according to body absorption, body weight, patient's age, sex, health status, diet, administration time, administration method, excretion rate, and disease severity. The pharmaceutical composition of the present invention is prepared in consideration of an effective amount range, and the unit dosage form formulated in this way is a specialized dosage method according to the individual's needs and the judgment of experts to monitor or observe the administration of the drug as necessary. It can be used or administered several times at regular time intervals. Specifically, the pharmaceutical composition of the present invention can be administered at 0.0001 to 1000 mg/kg per day based on the amount of Bauhinia extract, more specifically at 0.01 to 100 mg/kg per day, and the administration is limited to one day. It may be administered once, or may be administered several times.
또 다른 하나의 양태로서, 본 발명은 상기 바우히니아 추출물 및 이의 분획물을 유효성분으로 포함하는 약학 조성물을 개체에 투여하는 단계를 포함하는, 인지기능 장애의 예방 또는 치료 방법을 제공할 수 있다.As another aspect, the present invention may provide a method for preventing or treating cognitive dysfunction, comprising administering to a subject a pharmaceutical composition comprising the Bauhinia extract and its fraction as an active ingredient.
이때, 상기 바우히니아, 추출물, 분획물, 치매, 인지장애, 예방 및 치료의 정의는 상기에서 설명한 바와 같다.At this time, the definition of the Bauhinia, extract, fraction, dementia, cognitive impairment, prevention and treatment are as described above.
본 발명의 용어, "투여"란, 적절한 방법으로 개체에게 소정의 물질을 도입하는 것을 의미하며 상기 조성물의 투여 경로는 목적 조직에 도달할 수 있는 한 어떠한 일반적인 경로를 통하여 투여될 수 있다. 복강내 투여, 정맥내 투여, 근육 내 투여, 피하 투여, 피내 투여, 경구 투여, 국소 투여, 비내 투여, 폐내 투여, 직장 내 투여될 수 있으나, 이에 제한되지는 않는다. The term "administration" of the present invention means to introduce a predetermined substance into an individual in an appropriate manner, and the route of administration of the composition can be administered through any general route as long as it can reach the target tissue. Intraperitoneal administration, intravenous administration, intramuscular administration, subcutaneous administration, intradermal administration, oral administration, topical administration, intranasal administration, intrapulmonary administration, intrarectal administration, but are not limited thereto.
본 발명의 용어, "개체"란, 인지기능 장애가 발병하였거나 발병할 수 있는 인간을 포함한 모든 동물을 의미한다. 구체적인 예로, 인간을 포함한 포유동물일 수 있다.The term "individual" of the present invention means all animals, including humans, who may or may have a cognitive impairment. As a specific example, it may be a mammal, including a human.
또 다른 하나의 양태로서, 본 발명은 바우히니아 추출물을 포함하는 인지기능 장애의 예방 또는 개선용 건강기능식품 조성물을 제공한다.In another aspect, the present invention provides a health functional food composition for the prevention or improvement of cognitive dysfunction comprising a Bauhinia extract.
이때, 상기 바우히니아, 추출물, 분획물, 인지장애, 예방 및 치료의 정의는 상기에서 설명한 바와 같다.At this time, the definition of the Bauhinia, extract, fraction, cognitive impairment, prevention and treatment is as described above.
본 발명의 용어, "개선"이란, 본 발명의 바우히니아 추출물 또는 이의 분획물을 포함하는 조성물의 투여로 치료되는 상태와 관련된 파라미터, 예를 들면 증상의 정도를 적어도 감소시키는 모든 행위를 의미한다.The term "improvement" of the present invention means any action that at least reduces the parameters associated with the condition being treated by administration of a composition comprising the Bauhinia extract of the present invention or a fraction thereof, for example, the severity of symptoms.
본 발명의 조성물을 건강기능식품 첨가물로 사용할 경우, 상기 바우히니아 추출물을 그대로 첨가하거나 다른 식품 또는 식품 성분과 함께 사용할 수 있고, 통상의 방법에 따라 적절하게 사용할 수 있다. 유효 성분의 혼합량은 사용 목적(예방, 건강 또는 치료적 처치)에 따라 적합하게 결정될 수 있으며, 본 발명의 조성물은 친환경적이며 안정성 면에서 문제가 없기 때문에 혼합량에 큰 제한은 없다.When the composition of the present invention is used as a dietary supplement, the Bauhinia extract may be added as it is or used with other foods or food ingredients, and may be suitably used according to a conventional method. The mixing amount of the active ingredient can be appropriately determined according to the purpose of use (prevention, health or therapeutic treatment), and the composition of the present invention is environmentally friendly and there is no problem in terms of stability, so there is no significant limitation on the mixing amount.
본 발명의 건강기능식품 조성물은, 일상적으로 섭취하는 것이 가능하기 때문에 인지기능 장애 개선 효과를 기대할 수 있으므로, 건강 증진 목적으로 매우 유용하게 사용될 수 있다.Since the health functional food composition of the present invention can be expected to be ingested on a daily basis, an effect of improving cognitive dysfunction can be expected, and thus can be very useful for health promotion purposes.
본 발명의 용어, “건강기능식품”이란, 특정보건용 식품(food for special health use, FoSHU)과 동일한 용어로, 영양 공급 외에도 생체조절기능이 효율적으로 나타나도록 가공된 의학, 의료효과가 높은 식품을 의미한다. 여기서 '기능'이라 함은 인체의 구조 및 기능에 대하여 영양소를 조절하거나 생리학적 작용 등과 같은 보건용도에 유용한 효과를 얻는 것을 의미한다. 본 발명의 건강기능식품은 당 업계에서 통상적으로 사용되는 방법에 의하여 제조 가능하며, 상기 제조시에는 당 업계에서 통상적으로 첨가하는 원료 및 성분을 첨가하여 제조할 수 있다. 또한, 상기 건강기능식품의 제형 또한 식품으로 인정되는 제형이면 제한 없이 제조될 수 있다. 본 발명의 건강기능식품용 조성물은 다양한 형태의 제형으로 제조될 수 있으며, 일반 약품과는 달리 식품을 원료로 하여 약품의 장기 복용 시 발생할 수 있는 부작용 등이 없는 장점이 있고, 휴대성이 뛰어나므로, 본 발명의 건강기능식품은 인지기능 장애 개선 효과를 증진시키기 위한 보조제로 섭취가 가능하다.The term “health functional food” of the present invention is the same term as food for special health use (FoSHU), and is high in medical and medical effects processed to efficiently exhibit bioregulatory functions in addition to nutrition. Means Here, the term'function' means to obtain a useful effect for health use, such as adjusting nutrients or physiological effects on the structure and function of the human body. The health functional food of the present invention can be manufactured by a method conventionally used in the art, and may be prepared by adding raw materials and ingredients commonly added in the art. In addition, the formulation of the health functional food can also be prepared without limitation as long as the formulation is recognized as food. The composition for health functional food of the present invention can be manufactured in various types of formulations, and has the advantage of not having side effects that may occur when taking the drug for a long time using food as a raw material, unlike general drugs, and is excellent in portability. , The health functional food of the present invention can be ingested as an adjuvant to enhance the effect of improving cognitive impairment.
상기 건강기능식품은 일반식품에 비해 적극적인 건강유지나 증진효과를 가지는 식품을 의미하고, 건강보조식품(health supplement food)은 건강보조 목적의 식품을 의미한다. 경우에 따라, 건강기능식품, 건강식품, 건강보조식품의 용어는 호용된다.The health functional food refers to a food having an active health maintenance or enhancement effect compared to a general food, and a health supplement food means a food for health supplement purposes. In some cases, the terms health functional foods, health foods, and health supplements are used interchangeably.
구체적으로, 상기 건강기능식품은 본 발명의 화합물을 음료, 차류, 향신료, 껌, 과자류 등의 식품 소재에 첨가하거나, 캡슐화, 분말화, 현탁액 등으로 제조한 식품으로, 이를 섭취할 경우 건강상 특정한 효과를 가져오는 것을 의미하나, 일반 약품과는 달리 식품을 원료로 하여 약품의 장기 복용 시 발생할 수 있는 부작용이 없는 장점이 있다. Specifically, the health functional food is a food prepared by adding the compound of the present invention to food materials such as beverages, teas, spices, gums, confectionery, or encapsulated, powdered, suspensions, etc. It means to bring about an effect, but unlike general medicines, it has the advantage that there is no side effect that can occur when taking medicines for a long time using food as a raw material.
상기 건강기능식품 조성물은 생리학적으로 허용 가능한 담체를 추가로 포함할 수 있는데, 담체의 종류는 특별히 제한되지 않으며 당해 기술 분야에서 통상적으로 사용되는 담체 라면 어느 것이든 사용할 수 있다.The health functional food composition may further include a physiologically acceptable carrier, and the type of the carrier is not particularly limited, and any carrier commonly used in the art may be used.
또한, 상기 건강기능식품 조성물은 식품 조성물에 통상 사용되어 냄새, 맛, 시각 등을 향상시킬 수 있는 추가 성분을 포함할 수 있다. 예들 들어, 비타민 A, C, D, E, B1, B2, B6, B12, 니아신(niacin), 비오틴(biotin), 폴레이트(folate), 판토텐 산(panthotenic acid) 등을 포함할 수 있다. 또한, 아연(Zn), 철(Fe), 칼슘(Ca), 크롬(Cr), 마그네슘(Mg), 망간(Mn), 구리(Cu) 등의 미네랄; 및 라이신, 트립토판, 시스테인, 발린 등의 아미노산을 포함할 수 있다.In addition, the health functional food composition is commonly used in food composition may include an additional component that can improve the smell, taste, vision, and the like. For example, vitamin A, C, D, E, B1, B2, B6, B12, niacin, biotin, folate, pantotenic acid, and the like. In addition, minerals such as zinc (Zn), iron (Fe), calcium (Ca), chromium (Cr), magnesium (Mg), manganese (Mn), and copper (Cu); And amino acids such as lysine, tryptophan, cysteine, and valine.
또한, 상기 건강기능식품 조성물은 방부제(소르빈산 칼륨, 벤조산나트륨, 살리실산, 데히드로초산나트륨 등), 살균제(표백분과 고도 표백분, 차아염소산나트륨 등), 산화방지제(부틸히드록시아니졸(BHA), 부틸히드록시톨류엔(BHT) 등), 착색제(타르색소 등), 발색제(아질산 나트륨, 아초산 나트륨 등), 표백제(아황산나트륨), 조미료(MSG 글루타민산나트륨 등), 감미료(둘신, 사이클레메이트, 사카린, 나트륨 등), 향료(바닐린, 락톤류 등), 팽창제(명반, D-주석산수소칼륨 등), 강화제, 유화제, 증점제(호료), 피막제, 검기초제, 거품억제제, 용제, 개량제 등의 식품 첨가물(food additives)을 포함할 수 있다. 상기 첨가물은 식품의 종류에 따라 선별되고 적절한 양으로 사용될 수 있다.In addition, the health functional food composition is a preservative (potassium sorbate, sodium benzoate, salicylic acid, sodium dehydroacetate, etc.), fungicides (bleached and highly bleached, sodium hypochlorite, etc.), antioxidants (butyl hydroxyanisole (BHA), Butylhydroxytoluene (BHT, etc.), colorants (such as tar pigment), colorants (sodium nitrite, sodium nitrite, etc.), bleaching agents (sodium sulfite), seasonings (such as MSG sodium glutamate), sweeteners (dulcine, cyclate) , Saccharin, sodium, etc.), fragrances (vanillin, lactones, etc.), swelling agents (alum, D-potassium hydrogen sulphate, etc.), strengthening agents, emulsifiers, thickeners (foams), coating agents, gum starting agents, foam inhibitors, solvents, improvers, etc. May include food additives. The additive may be selected according to the type of food and used in an appropriate amount.
본 발명의 건강기능식품 조성물의 일 예로 건강음료 조성물로 사용될 수 있으며, 이 경우 통상의 음료와 같이 여러 가지 향미제 또는 천연 탄수화물 등을 추가 성분으로 함유할 수 있다. 상술한 천연 탄수화물은 포도당, 과당과 같은 모노사카라이드; 말토스, 수크로스와 같은 디사카라이드; 덱스트린, 사이클로덱스트린과 같은 폴리사카라이드; 자일리톨, 소르비톨, 에리트리톨 등의 당알콜 일 수 있다. 감미제는 타우마틴, 스테비아 추출물과 같은 천연 감미제; 사카린, 아스파르탐과 같은 합성 감미제 등을 사용할 수 있다. 상기 천연 탄수화물의 비율은 본 발명의 건강음료 조성물 100 mL 당 일반적으로 약 0.01 ～ 0.04 g, 구체적으로 약 0.02 ～ 0.03 g이 될 수 있다.As an example of the health functional food composition of the present invention, it can be used as a health drink composition, and in this case, it may contain various flavoring agents or natural carbohydrates, etc., as additional components, such as a normal beverage. The natural carbohydrates described above include monosaccharides such as glucose and fructose; Disaccharides such as maltose and sucrose; Polysaccharides such as dextrin and cyclodextrin; It may be a sugar alcohol such as xylitol, sorbitol, erythritol. Sweeteners include natural sweeteners such as taumatin and stevia extract; Synthetic sweeteners such as saccharin and aspartame. The ratio of the natural carbohydrate may be generally about 0.01 to 0.04 g, specifically about 0.02 to 0.03 g per 100 mL of the health drink composition of the present invention.
상기 외에 건강음료 조성물은 여러 가지 영양제, 비타민, 전해질, 풍미제, 착색제, 펙트산, 펙트산의 염, 알긴산, 알긴산의 염, 유기산, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알코올 또는 탄산화제 등을 함유할 수 있다. 그 밖에 천연 과일주스, 과일주스 음료, 또는 야채 음료의 제조를 위한 과육을 함유할 수 있다. 이러한 성분은 독립적으로 또는 혼합하여 사용할 수 있다. 이러한 첨가제의 비율은 크게 중요하진 않지만 본 발명의 건강음료 조성물 100 중량부당 0.01 ~ 0.1 중량부의 범위에서 선택되는 것이 일반적이다.In addition to the above, the health drink composition includes various nutrients, vitamins, electrolytes, flavoring agents, coloring agents, pectic acid, pectic acid salts, alginic acid, alginic acid salts, organic acids, protective colloidal thickeners, pH adjusting agents, stabilizers, preservatives, glycerin, Alcohol or carbonic acid. In addition, it may contain flesh for the manufacture of natural fruit juice, fruit juice beverage, or vegetable beverage. These ingredients can be used independently or in combination. The proportion of these additives is not particularly important, but is generally selected from 0.01 to 0.1 parts by weight per 100 parts by weight of the health drink composition of the present invention.
본 발명의 바우히니아 추출물을 포함하는 조성물은 아세틸콜린 분해효소 활성 및 아밀로이드 베타 응집을 억제시키고, 높은 항산화 효능 및 외부 자극으로부터 신경세포를 보호하는 효과를 보이므로, 인지기능 장애 예방, 치료 또는 개선하기 위한 의약품 또는 건강기능식품에 적용하여 이용할 수 있다.The composition comprising the Bauhinia extract of the present invention inhibits acetylcholine degrading enzyme activity and amyloid beta aggregation, and has high antioxidant efficacy and an effect of protecting neurons from external stimulation, thereby preventing, treating or improving cognitive dysfunction It can be applied to medicines or health functional foods for
도 1은 아세틸콜린 분해 효소에 대한 본 발명의 바우히니아 추출물의 효과를 보여주는 그래프이다(EEBC: 바우히니아 에탄올 추출물, BER: 양성 대조군 베르베린).
도 2는 아밀로이드 베타 응집에 대한 본 발명의 바우히니아 추출물의 효과를 보여주는 그래프이다(EEBC: 바우히니아 에탄올 추출물, Morin: 양성 대조군).
도 3은 ABTS 및 DPPH 라디칼에 대한 본 발명의 바우히니아 추출물의 효과를 보여주는 그래프이다.(EEBC: 바우히니아 에탄올 추출물, AA: 양성 대조군, 아스코르브산)
도 4는 HT22 세포를 이용한 신경세포에 대한 본 발명의 바우히니아 추출물의 효과를 보여주는 그래프이다. (EEBC: 바우히니아 에탄올 추출물, ### P<0.001 versus 무처리군, * P<0.05, ** P<0.01 versus H2O2 단독 처리군)1 is a graph showing the effect of the present invention Bauhinia extract on acetylcholine degrading enzyme (EEBC: Bauhinia ethanol extract, BER: positive control berberine).
Figure 2 is a graph showing the effect of the present invention Bauhinia extract on amyloid beta aggregation (EEBC: Bauhinia ethanol extract, Morin: positive control).
3 is a graph showing the effect of the present invention Bauhinia extract on ABTS and DPPH radicals. (EEBC: Bauhinia ethanol extract, AA: positive control, ascorbic acid)
4 is a graph showing the effect of the Bauhinia extract of the present invention on neurons using HT22 cells. (EEBC: Bauhinia ethanol extract, ### P <0.001 versus no treatment, * P <0.05, ** P <0.01 versus H 2 O 2 alone treatment)
이하 본 발명을 실시예를 통하여 보다 상세하게 설명한다. 그러나 이들 실시예는 본 발명을 예시적으로 설명하기 위한 것으로, 본 발명의 범위가 이들 실시예에 의해 한정되는 것은 아니다.Hereinafter, the present invention will be described in more detail through examples. However, these examples are for illustrative purposes only, and the scope of the present invention is not limited by these examples.
실시예 1 : 바우히니아 소지 추출물의 제조Example 1: Preparation of Bauhinia possession extract
바우히니아(Bauhinia coccinea) 소지 추출물은 소지 30g에 70% 에탄올 300 mL를 첨가한 후, 상온에서 48시간 동안 추출하는 과정을 3회 반복하여 추출물을 얻었다. 상기 바우히니아 소지 추출물을 여과지로 여과한 추출액은 40℃에서 농축기로 감압 농축하였다. 상기 농축된 추출물에 정제수를 첨가하여 현탁시킨 후 동결건조기로 건조하고 균질화하여 에탄올 추출물(Ethanol extract of Bauhinia coccinea,이하 EEBC라 함)을 수득하였다. Bauhinia (Bauhinia coccinea) possession extract, after adding 300 mL of 70% ethanol to 30 g of the possession, the process of extracting for 48 hours at room temperature was repeated 3 times to obtain an extract. The extract obtained by filtering the Bauhinia bovine extract with filter paper was concentrated under reduced pressure with a concentrator at 40°C. Purified water is added to the concentrated extract and suspended, then dried with a lyophilizer and homogenized to give an ethanol extract (Ethanol extract of Bauhinia). coccinea, hereinafter referred to as EEBC).
실시예Example 2 : 2 : 바우히니아Bauhinia 소지 추출물의 인지기능 장애 생리지표 분석 Analysis of physiological indicators of cognitive impairment of bovine extract
실시예Example 2-1 : 아세틸콜린 분해효소( 2-1: Acetylcholine degrading enzyme ( acetylcholineacetylcholine esterase, esterase, AChEAChE ) 활성 저해 효능 측정) Activity inhibition efficacy measurement
아세틸콜린 분해효소 활성은 Ellman법을 변형하여 분광 광도법을 이용하여 측정하였다. 활성 분석을 위한 완충용액(어세이 버퍼)은 0.1 M sodium phosphate buffer(pH 7.3, 이하 A-버퍼라 함)를 사용하였고, 아세틸콜린 분해효소는 0.1% BSA/H2O를 함유하는 어세이 버퍼에 녹여 최종 농도 35.2 mU/mL인 것을 사용하였다. 기질 acetylthiocholine iodide와 발색 시약 DTNB (5,5'-dithiobis(2-nitrobenzoic acid)) 를 A-버퍼에 녹여 각각 10 mM의 농도로 일정량씩 분주하여 -80oC에 보관하고, 실험 시 최종 농도 0.5 mM인 기질-발색 시약 혼합물을 수득하였다. 시료는 실시예 1에서 제조한 바우히니아 소지 추출물을 0.1 M sodium phosphate buffer (pH 8.0)에 녹여 최종 농도 100 ug/mL이 된 것을 사용하였다. 효소 반응은 상온에서 실시하였고, 다음과 같이 전개하였다. 50 uL의 시료와 50 uL의 기질-발색 시약 혼합액을 섞어주고, 10 분간 전배양한 후, 아세틸콜린 분해효소를 처리하고 60분간 반응시켰다. 흡광도는 Epoch 마이크로플레이트 분광광도계를 이용하여 412 nm에서 측정하였다. 양성 대조군으로는 베르베린(berberine)을 사용하였다(도 1). Acetylcholine degrading enzyme activity was measured using a spectrophotometric method by modifying the Ellman method. As a buffer solution (assay buffer) for activity analysis, 0.1 M sodium phosphate buffer (pH 7.3, hereinafter referred to as A-buffer) was used, and the acetylcholine degrading enzyme was assay buffer containing 0.1% BSA/H 2 O. And dissolved in a final concentration of 35.2 mU/mL. Dissolve the substrate acetylthiocholine iodide and the coloring reagent DTNB (5,5'-dithiobis(2-nitrobenzoic acid)) in an A-buffer, dispense a certain amount at a concentration of 10 mM, and store it at -80 o C. A substrate-color reagent mixture in mM was obtained. As a sample, the Bauhinia bovine extract prepared in Example 1 was dissolved in 0.1 M sodium phosphate buffer (pH 8.0) to obtain a final concentration of 100 ug/mL. The enzyme reaction was carried out at room temperature, and was developed as follows. A mixture of 50 uL sample and 50 uL of substrate-coloring reagent was mixed, pre-incubated for 10 minutes, treated with acetylcholine degrading enzyme, and reacted for 60 minutes. Absorbance was measured at 412 nm using an Epoch microplate spectrophotometer. As a positive control, berberine was used (FIG. 1 ).
도 1에서 보듯이, 바우히니아 추출물의 아세틸콜린 분해효소의 저해 활성은 바우히니아 추출물의 농도가 증가함에 따라 저해활성이 증가하는 농도의존적인 경향을 보였으며, 50 ug/mL에서 67.25%로 양성 대조군보다 높은 저해활성을 보였고, 특히 100 ug/mL에서는 85.77%의 높은 저해 활성을 보였다. As shown in Figure 1, the inhibitory activity of the acetylcholine degrading enzyme of the Bauhinia extract showed a concentration-dependent tendency to increase the inhibitory activity as the concentration of the Bauhinia extract increased, from 50 ug/mL to 67.25% It showed higher inhibitory activity than positive control, especially at 100 ug/mL, high inhibitory activity of 85.77%.
상기 결과로부터, 바우히니아 추출물은 아세틸콜린 분해 효소 저해 활성을 가짐으로써 치매 및 인지장애 예방에 효과적일 수 있음을 알 수 있었다. From the above results, it was found that the Bauhinia extract can be effective in preventing dementia and cognitive disorder by having acetylcholine degrading enzyme inhibitory activity.
실시예Example 2-2 : 아밀로이드 베타 응집 억제 효능 측정 2-2: Amyloid beta aggregation inhibition efficacy measurement
아밀로이드 베타 응집 억제 측정은 형광 분석법(Thioflavin T assay)을 이용하였다. 아밀로이드 베타 (Aβ 1 -42) 펩티드는 영하 80℃에서 보관하였으며, 측정 시 사용한 최종 농도는 100 μg/mL로 하였다. 형광물질로 사용하는 2 mM의 티오플라빈 T는 활성 분석을 위한 완충 용액(어세이 버퍼) (50mM Tris/150mM NaCl(pH 7.2), 20mM HEPES/150mM NaCl(pH 7.2), 10mM phosphate/150mM NaCl(pH 8.0)에 녹여 제조하였다. 시료는 실시예 1에서 제조한 바우히니아 소지 추출물을 어세이 버퍼에 녹여 최종 농도 100 μg/mL인 것을 사용하였다. Aβ 1 -42 응집억제 정도를 측정하기 위하여 96 웰 플레이트(블랙 마이크로플레이트)에 티오플라빈 T 10 μL와 Aβ 1 -42 85 μL를 넣어 응집시키고, 일정 농도로 만든 시료 5 μL와 혼합하여 형광 분광 분석기로 측정하였다. 이때 사용한 형광 분광 분석기의 파장값은 440 nm/484 nm(여기/방출)이며, 37℃에서 20분 간격으로 총 2시간 측정하였다. 활성 비교를 위하여 양성 대조군으로 모린(morin)을 사용하였다(도 2). For the measurement of amyloid beta aggregation inhibition, fluorescence analysis (Thioflavin T assay) was used. The amyloid beta (A β 1 -42 ) peptide was stored at minus 80°C, and the final concentration used in the measurement was 100 μg/mL. The 2 mM thioflavin T used as a fluorescent material is a buffer solution (assay buffer) for activity analysis (50 mM Tris/150 mM NaCl (pH 7.2), 20 mM HEPES/150 mM NaCl (pH 7.2), 10 mM phosphate/150 mM NaCl (pH 8.0) was prepared by dissolving the Bauhinia bovine extract prepared in Example 1 in an assay buffer and using a final concentration of 100 μg/mL A β 1 -42 To measure the degree of aggregation inhibition To this end, 10 μL of thioflavin T and 85 μL of A β 1 -42 were added to a 96-well plate (black microplate), aggregated, and mixed with 5 μL of a sample prepared at a constant concentration, and measured with a fluorescence spectroscopy. The wavelength value of the analyzer was 440 nm/484 nm (excitation/emission), and a total of 2 hours was measured at an interval of 20 minutes at 37° C. Morin was used as a positive control for activity comparison (FIG. 2 ).
도 2에서 보듯이, 바우히니아 추출물의 아밀로이드 베타 응집 억제 효능은 바우히니아 소지 추출물의 농도가 증가함에 따라 저해활성이 증가하는 농도의존적인 경향을 보였으며, 50 ug/mL에서는 63.5%로 양성 대조군과 비슷한 저해활성을 보였고, 100 ug/mL에서는 74.9%의 높은 저해 활성을 보였다. As shown in FIG. 2, the effect of inhibiting amyloid beta aggregation of the Bauhinia extract showed a concentration-dependent tendency to increase inhibitory activity as the concentration of the Bauhinia-bearing extract increased, and was positive at 63.5% at 50 ug/mL. It showed similar inhibitory activity to the control group and a high inhibitory activity of 74.9% at 100 ug/mL.
상기 결과로부터, 바우히니아 추출물은 아밀로이드 베타 응집 억제 효능을 가짐으로써 치매 및 인지장애 예방에 효과적일 수 있음을 알 수 있었다. From the above results, it was found that the Bauhinia extract can be effective in preventing dementia and cognitive disorder by having amyloid beta aggregation inhibitory effect.
실시예Example 3 : 항산화 효능 측정 3: Antioxidant efficacy measurement
실시예Example 3-1 : 3-1: ABTSABTS 라디칼 Radical 소거능Erasing ability 측정 Measure
ABTS(3-ethyl-benzothiazoline-6-sulfonic acid) 라디칼을 이용한 항산화능 측정은 ABTS+· cation decol orization 어세이 방법을 96 웰 플레이트를 이용하는 방법에 맞게 수정하여 실시하였다. 7mM ABTS와 2.45 mM potassium persulfate를 균일하게 혼합하여실온인 암소에서 24시간 동안 방치하여 ABTS 양이온 (ABTS+)을 형성시켰다. 그런 다음, 743 nm에서 0.7의 흡광도 값을 갖도록 PBS로 희석하였다. 96 웰 플레이트에 ABTS+용액과 시료를 각각 100μl씩 동량으로 혼합하여 실온에서 30분간 반응시킨 후, Epoch 마이크로플레이트 분광광도계를 사용하여 743 nm에서 흡광도를 측정하였다. 각 시료의 라디칼 소거활성은 용매인 PBS를 대조군으로 하여 대조군에 대한 라디칼 소거능을 백분율로 나타냈다. 활성 비교를 위하여 양성대조군으로 비타민 C(AA, 아스코르브산)를 사용하였다(도 3의 (A)). The antioxidant capacity measurement using the ABTS (3-ethyl-benzothiazoline-6-sulfonic acid) radical was performed by modifying the ABTS+ cation decol orization assay method according to the method using a 96-well plate. 7 mM ABTS and 2.45 mM potassium persulfate were uniformly mixed and allowed to stand for 24 hours in room temperature cows to form ABTS cations (ABTS+). It was then diluted with PBS to have an absorbance value of 0.7 at 743 nm. After the ABTS+ solution and the sample were mixed in an equal amount of 100 μl each in a 96-well plate and reacted for 30 minutes at room temperature, absorbance was measured at 743 nm using an Epoch microplate spectrophotometer. The radical scavenging activity of each sample was expressed as a percentage of the radical scavenging ability of the control group using PBS as a solvent as a control. Vitamin C (AA, ascorbic acid) was used as a positive control for activity comparison (Fig. 3(A)).
도 3의 (A)에서 보듯이, 3.125 또는 6.25 ug/mL 농도의 바우히니아 추출물을 처리한 경우에는, 각각 45.41% 또는 82.30%의 ABTS 라디칼 소거능을 나타내었고, 12.5 ug/mL 농도 이상(12.5~400 ug/mL)의 추출물을 처리한 경우에는 100%의 ABTS 라디칼 소거능을 나타냄을 확인하였다.As shown in Figure 3 (A), when treated with a 3.125 or 6.25 ug / mL concentration of Bauhinia extract, 45.41% or 82.30% of ABTS radical scavenging ability, respectively, was more than 12.5 ug / mL concentration (12.5 ~400 ug/mL), it was confirmed that it exhibits 100% ABTS radical scavenging ability.
따라서, 바우히니아 추출물은 거의 모든 농도에서 양성 대조군으로 사용된 아스코르브산보다 높은 라디칼 소거능을 나타냄을 알 수 있었다.Therefore, it was found that the Bauhinia extract exhibited a higher radical scavenging ability than ascorbic acid used as a positive control at almost all concentrations.
실시예Example 3-2 : 3-2: DPPHDPPH 라디칼 Radical 소거능Erasing ability 측정 Measure
DPPH(1-1-diphenyl-2-picrylhydrazyl) 라디칼에 대한 시료의 항산화 활성 평가는 96 웰 플레이트을 이용하여 실시하였다. 96 웰 플레이트에 0.15 mM 의 DPPH 용액과 시료를 각각 100μl씩 동량으로 균일하게 혼합하여 실온에서 30분간 반응시킨 후, 517 nm에서 흡광도를 측정하였다. 각 처방 추출물의 항산화 활성은 용매인 DMSO를 대조군으로 하여 대조군에 대한 라디칼 소거능을 백분율로 나타내었다. 활성비교를 위하여 양성 대조군으로 비타민 C(AA, 아스코르브산)를 사용하였다(도 3의 (B)). Evaluation of the antioxidant activity of the sample against the DPPH (1-1-diphenyl-2-picrylhydrazyl) radical was carried out using a 96 well plate. After absorbing 0.15 mM DPPH solution and a sample in a 96-well plate in an equal amount of 100 μl each and reacting for 30 minutes at room temperature, absorbance was measured at 517 nm. The antioxidant activity of each prescription extract was expressed as a percentage of the radical scavenging ability to the control group using DMSO as a control group as a control group. Vitamin C (AA, ascorbic acid) was used as a positive control for active comparison (FIG. 3(B)).
도 3의 (B)에서 보듯이, 바우히니아 추출물의 DPPH 라디칼 소거능은 3.125 내지 400 ug/mL에서 상기 추출물의 농도 의존적(37.66~88.50%)로 유의적으로 증가하는 경향을 보였고, 25 ug/mL 이상의 농도에서는 양성 대조군으로 사용된 아스코르브산과 비슷한 수준의 라디칼 소거능을 나타냈다. As shown in FIG. 3(B), the DPPH radical scavenging ability of the Bauhinia extract showed a tendency to increase significantly from 3.125 to 400 ug/mL depending on the concentration of the extract (37.66 to 88.50%), and 25 ug/ At concentrations above mL, it showed a radical scavenging ability similar to that of ascorbic acid used as a positive control.
상기 실시예 3-1 및 3-2의 결과를 종합하면, 바우히니아 추출물의 항산화활성이 우수함을 알 수 있다. 또한, 400 ug/mL의 바우히니아 추출물의 DPPH 소거능(88.50%) 보다, 같은 농도에서의 ABTS 소거능(100%)이 더 높은 이유는 DPPH 분석의 경우 자유 라디칼을 소거하지만, ABTS는 양이온 라디칼을 소거하는 차이를 가지며, 두 기질과 반응하는 반응물과의 결합 정도가 상이하여 라디칼 소거능에 차이가 있는 것으로 보고되고 있다 (J Korean Soc Food Sci Nutr 36, 250-254).Summarizing the results of Examples 3-1 and 3-2, it can be seen that the antioxidant activity of the Bauhinia extract is excellent. In addition, the reason why the ABTS scavenging ability (100%) at the same concentration is higher than the DPPH scavenging ability (88.50%) of the Bauhinia extract at 400 ug/mL is that free radical scavenging is performed in the case of DPPH analysis, but ABTS scavenges cationic radicals. It has a difference in scavenging, and it has been reported that there is a difference in radical scavenging ability due to a different binding degree between reactants reacting with two substrates (J Korean Soc Food Sci Nutr 36, 250-254).
실시예Example 4 : HT22 세포에 의한 신경세포 보호 효능 4: Efficacy of protecting neurons by HT22 cells
실시예Example 4-1 : HT22 세포 배양 4-1: HT22 cell culture
HT22 세포는 10% FBS가 첨가된 DMEM 배지를 이용하여 37℃의 5% CO2 배양기에서 배양하였다.HT22 cells were cultured in a 5% CO 2 incubator at 37° C. using DMEM medium with 10% FBS added.
실시예Example 4-2 : 신경세포 보호 활성 측정 4-2: Measurement of neuronal protective activity
신경 세포 손상을 유도하기 위하여 HT22 세포에 250 μM 과산화수소(H2O2)를 6시간 처리하였으며, H2O2단독 처리군과 시료와 H2O2 동시 처리군의 세포 생존율 변화를 비교하여 세포 보호 효능을 판단하였다. 양성 대조군으로 carvedilol을 사용하였다(도 4). In order to induce neuronal damage, HT22 cells were treated with 250 μM hydrogen peroxide (H 2 O 2 ) for 6 hours, and the cell viability changes of the H 2 O 2 alone treatment group and the sample and H 2 O 2 simultaneous treatment group were compared. The protective efficacy was judged. Carvedilol was used as a positive control (Fig. 4).
도 4에서 보듯이, HT22 세포 생존율은 아무 처리도 하지 않은 대조군 100% 대비 H2O2 단독 처리군에서는 55.20% 생존율을 나타냈고, 바우히니아 추출물 및 H2O2 동시 처리군에서는 농도가 증가함에 따라 점차적으로 세포 생존율이 증가하는 것으로 나타났으며, 특히 50 ㎍/mL 농도에서 71.99%의 생존율을 보이며 H2O2 처리군 대비 16.79%정도의 신경세포 보호효과를 보였다. As shown in Figure 4, HT22 cell viability showed 55.20% survival rate in the H 2 O 2 alone treatment group compared to the
상기 결과로부터, 바우히니아 추출물이 외부자극에 대하여 신경세포를 보호함으로써, 신경세포의 생존율을 향상시키는 효과를 나타냄을 알 수 있었다.From the above results, it was found that the Bauhinia extract showed an effect of improving the survival rate of nerve cells by protecting the nerve cells against external stimulation.
이상의 설명으로부터, 본 발명이 속하는 기술분야의 당업자는 본 발명이 그 기술적 사상이나 필수적 특징을 변경하지 않고서 다른 구체적인 형태로 실시될 수 있다는 것을 이해할 수 있을 것이다. 이와 관련하여, 이상에서 기술한 실시예들은 모든 면에서 예시적인 것이며 한정적인 것이 아닌 것으로 이해해야만 한다. 본 발명의 범위는 상기 상세한 설명보다는 후술하는 특허 청구범위의 의미 및 범위 그리고 그 등가 개념으로부터 도출되는 모든 변경 또는 변형된 형태가 본 발명의 범위에 포함되는 것으로 해석되어야 한다.From the above description, those skilled in the art to which the present invention pertains will appreciate that the present invention may be implemented in other specific forms without changing its technical spirit or essential characteristics. In this regard, it should be understood that the embodiments described above are illustrative in all respects and not restrictive. The scope of the present invention should be construed as including the meaning and scope of the claims, which will be described later, rather than the above detailed description, and all modified or modified forms derived from the equivalent concepts thereof.
Claims (9)
상기 인지기능 장애는 건망증, 알츠하이머병, 치매, 파킨슨 병, 피크병, 및 헌팅톤병으로 이루어지는 군에서 선택되는 퇴행성 뇌질환인 것인 약학 조성물.According to claim 1,
The cognitive dysfunction is a pharmaceutical composition that is a degenerative brain disease selected from the group consisting of forgetfulness, Alzheimer's disease, dementia, Parkinson's disease, Peak disease, and Huntington's disease.
상기 바우히니아 코키니아 추출물은 소지 추출물인 것인 약학 조성물.According to claim 1,
The Bauhinia cochinia extract is a pharmaceutical composition that is a possession extract.
상기 바우히니아 코키니아 추출물은 바우히니아 코키니아를 물, C1 내지 C4 알코올 또는 이들의 혼합용매로 추출하여 수득한 것인 약학 조성물.According to claim 1,
The Bauhinia cochinia extract is a pharmaceutical composition obtained by extracting Bauhinia cochinia with water, C1 to C4 alcohol or a mixed solvent thereof.
상기 바우히니아 코키니아 추출물은 아세틸콜린 분해효소 억제, 아밀로이드 베타 응집 억제, 항산화 및 신경세포 보호 효과를 가지는 것인 약학 조성물.According to claim 1,
The Bauhinia cochinia extract is a pharmaceutical composition having acetylcholine degrading enzyme inhibition, amyloid beta aggregation inhibition, antioxidant and neuronal protective effect.
Health functional food composition for preventing or improving cognitive impairment, comprising Bauhinia cochinia extract.
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