KR20100060949A - Composition for protecting nerve cells - Google Patents
Composition for protecting nerve cells Download PDFInfo
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- KR20100060949A KR20100060949A KR1020080119765A KR20080119765A KR20100060949A KR 20100060949 A KR20100060949 A KR 20100060949A KR 1020080119765 A KR1020080119765 A KR 1020080119765A KR 20080119765 A KR20080119765 A KR 20080119765A KR 20100060949 A KR20100060949 A KR 20100060949A
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- peach leaf
- leaf extract
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- peach
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/105—Plant extracts, their artificial duplicates or their derivatives
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/73—Rosaceae (Rose family), e.g. strawberry, chokeberry, blackberry, pear or firethorn
- A61K36/736—Prunus, e.g. plum, cherry, peach, apricot or almond
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2200/00—Function of food ingredients
- A23V2200/30—Foods, ingredients or supplements having a functional effect on health
- A23V2200/322—Foods, ingredients or supplements having a functional effect on health having an effect on the health of the nervous system or on mental function
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
- A61K2236/331—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using water, e.g. cold water, infusion, tea, steam distillation, decoction
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
- A61K2236/333—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using mixed solvents, e.g. 70% EtOH
Abstract
Description
본 발명은 복숭아 잎 추출물을 유효 성분으로 포함하는 신경세포 보호용 조성물에 관한 것이다. The present invention relates to a neuronal cell protective composition comprising a peach leaf extract as an active ingredient.
뇌졸중은 심장질환과 암에 이어 사망원인 3위이고 만성적 장애를 유발하며(Wong KS, Chen C, Ng PW, Tsoi TH, Li HL, Fong WC, et al. :Lowmolecular weight heparin compared with aspirin for the treatment of acute ischaemic stroke in Asian patients with large artery occlusive disease: a randomised study., Lancet Neurol (2007)6:407-13), 인류의 1/6이 혈관성 질환으로 고통 받고 있으나, 효과적인 뇌혈관성 질환 치료제는 아직 없다(Seshadri S, Beiser A, Kelly-Hayes M, Kase CS, Au R, Kannel WB, et al.:The lifetime risk of stroke: estimates from the Framingham study, Stroke (2006)37:345-50). 허혈성 뇌혈관 질환은 혈액 공급의 장애로 산소와 포도당의 감소에 의해 조직에 손상을 주는 질병이다. 그러나 더 심각한 조직 손상은 혈액이 재혈류 되었을 때 발생하며 이 허혈성 뇌경색에 의한 뇌세포 손상의 병리학적인 메커니즘은 복잡하고 다요인적이 다(Maruyama et al.: Protective Properties of Neoechinulin A against SIN-1-Induced Neuronal Cell Death, J. Biochem. 136, 81-87 (2004), Meenakshisundaram, Thiyagarajan, Chaman Lal, Kaul and Shyam Sundar,Sharma. Neuroprotective efficacy and therapeutic time window of peroxynitrite decomposition catalysts in focal cerebral ischemia in rats.: British Journal of Pharmacology, (2004) 142, 899-911). 현재까지의 많은 연구결과들은 허혈후 재혈류 동안 뇌에서 활성산소종들이 생성된다고 보고하고 있으며, 또한 뇌경색 후 신경손상에 활성산소종들이 관여한다는 연구도 활발히 진행되어 있다(Meenakshisundaram Thiyagarajan, Shyam S. Sharma*,: Neuroprotective effect of curcumin in middle cerebral artery occlusion induced focal cerebral ischemia in rats, Life Sciences 74 (2004)969-85). 활성산소종(ROS)들의 몇몇 종들은 허헐 후 재혈류 후에 생성되어 뇌허혈 후 뇌손상에 중요한 역할을 한다고 알려져 있다(Imaizumi, S., Kayama, T., Suzuki, J.,: Chemiluminescence in hypoxic brain-the first report, Correlation between energy metabolism and free radical reaction. Stroke. (1984);15 (6), 1061-1065). 특히 뉴런은 허혈성 손상, 미토콘드리아 기능 손실, 글루타메이트 수용체의 활성화, 칼슘 과잉축적 등에 의해 손상되기 쉽다( Choi DW. : Ischemia-induced neuronal apoptosis, Curr Opin Neurobiol. (1996); 6:667-72.). Stroke is the third leading cause of death following heart disease and cancer and causes chronic disorders (Wong KS, Chen C, Ng PW, Tsoi TH, Li HL, Fong WC, et al.:Lowmolecular weight heparin compared with aspirin for the treatment of acute ischaemic stroke in Asian patients with large artery occlusive disease: a randomised study., Lancet Neurol (2007) 6: 407-13), although one-sixth of humans suffer from vascular disease, effective treatment for cerebrovascular disease (Seshadri S, Beiser A, Kelly-Hayes M, Kase CS, Au R, Kannel WB, et al .: The lifetime risk of stroke: estimates from the Framingham study, Stroke (2006) 37: 345-50). Ischemic cerebrovascular disease is a disorder of the blood supply that damages tissues by reducing oxygen and glucose. However, more severe tissue damage occurs when blood is re-reflowed, and the pathological mechanism of brain cell damage caused by ischemic cerebral infarction is complex and multifactorial (Maruyama et al .: Protective Properties of Neoechinulin A against SIN-1-Induced). Neuronal Cell Death, J. Biochem. 136, 81-87 (2004), Meenakshisundaram, Thiyagarajan, Chaman Lal, Kaul and Shyam Sundar, Sharma. Neuroprotective efficacy and therapeutic time window of peroxynitrite decomposition catalysts in focal cerebral ischemia in rats .: British Journal of Pharmacology, (2004) 142, 899-911). Many studies to date report that reactive oxygen species are produced in the brain during ischemia and revascularization, and active oxygen species are involved in neuronal damage after cerebral infarction (Meenakshisundaram Thiyagarajan, Shyam S. Sharma). * ,: Neuroprotective effect of curcumin in middle cerebral artery occlusion induced focal cerebral ischemia in rats, Life Sciences 74 (2004) 969-85). Some species of reactive oxygen species (ROS) are known to have a role in brain injury after cerebral ischemia, which is produced after rebleeding after humility (Imaizumi, S., Kayama, T., Suzuki, J., Chemiluminescence in hypoxic brain the first report, Correlation between energy metabolism and free radical reaction.Stroke. (1984); 15 (6), 1061-1065). In particular, neurons are susceptible to damage by ischemic injury, loss of mitochondrial function, activation of glutamate receptors, calcium overaccumulation (Cho DW, Ischemia-induced neuronal apoptosis, Curr Opin Neurobiol. (1996); 6: 667-72.).
ATP 대사는 하이포잔틴의 축적을 유도하는 한편 허혈이 일어나지 않은 조직에서 잔틴산화효소는 니코틴아마이드 아데닌 디뉴클레오티드 환원성 수소화 효소로 서 존재한다. (Morimoto, K., Tagawa, K., Hayakawa, T., Watanabe, F. and Mogami, :H. Cellular level of purine compounds in ischemic gerbil brain by high performance liquid chromatography. J. Neurochem. (1982); 38, 833-835.). 허혈시 칼슘이온에 의해 활성화된 단백분해 효소들은 비가역적으로 잔틴탈수소효소를 잔틴산화효소로 전환시키고 잔틴산화제는 잔틴을 더욱 더 산화시켜 요산, 활성산소종을 발생시킨다(Parks, D. A. and Granger, D. N. :Xanthine oxidase: biochemistry, distribution and physiology. Acta Physiol. Scand. Suppl., (1986);548, 87-99.). NO(nitric oxide)는 L-아르기닌으로부터 효소적으로 합성되고 허혈에 의해서 상당히 많이 증가한다( Wei, G., Dawson, V. L. and Zweier, J. L.: Role of neuronaland endothelial nitric oxide synthase in nitric oxide generation in the brain following cerebral ischemia, Biochim. Biophys. Acta (1999);1455, 23-34.). 그리고 수퍼옥사이드 이온(superoxide anion) 및 하이드록실 라디칼(hydroxyl radical)은 지질과산화를 유도함으로써 세포막의 파괴에 관여하고 iNOS(Inducible nitric oxide synthase)는 허혈 후 재혈류에 의해 상향 조절된다. 과량의 산화질소(nitric oxide)는 수퍼옥사이드와 반응하여 퍼옥시나이트라이트(peroxynitrite)를 생성하며 생성된 퍼옥시나이트라이트는 인지질 이중막을 자유로이 통과하여 지질, 단백질과 DNA 등 다양한 분자들과 반응하여 세포사멸을 유도할 수 있다(Li, J.; Su, J.; Li, W.; Liu, W.; Altura, B. T.; Altura, B. M.:Peroxynitrite induces apoptosis in canine cerebral vascular muscle cells: possible relation to neurodegenerative diseases and strokes., Neurosci. Lett. 2003, 350, 173-177.). 이러한 일련의 반응들은 신경세포 손상으로 이어지고, 이 손상은 세포내의 기능장애 결과를 초래한다. ATP metabolism induces hypoxanthine accumulation, while xanthine oxidase is present as nicotinamide adenine dinucleotide reductive hydrogenase in tissues in which ischemia does not occur. (Morimoto, K., Tagawa, K., Hayakawa, T., Watanabe, F. and Mogami,: H. Cellular level of purine compounds in ischemic gerbil brain by high performance liquid chromatography. J. Neurochem. (1982); 38 , 833-835.). Proteolytic enzymes activated by calcium ions in ischemia irreversibly convert xanthine dehydrogenase to xanthine oxidase, and xanthine oxidant further oxidizes xanthine to generate uric acid and reactive oxygen species (Parks, DA and Granger, DN). : Xanthine oxidase:.... . biochemistry, distribution and physiology Acta Physiol Scand Suppl, (1986); 548, 87-99). NO (nitric oxide) is enzymatically synthesized from L-arginine and significantly increased by ischemia (Wei, G., Dawson, VL and Zweier, JL: Role of neuronaland endothelial nitric oxide synthase in nitric oxide generation in the brain following cerebral ischemia, Biochim. Biophys. Acta (1999); 1455, 23-34.). In addition, superoxide anion and hydroxyl radical induce lipid peroxidation to induce cell membrane destruction and iNOS (inducible nitric oxide synthase) is upregulated by re-blood flow after ischemia. Excess nitric oxide reacts with superoxide to produce peroxynitrite, and the resulting peroxynitrite freely passes through the phospholipid bilayer to react with various molecules such as lipids, proteins, and DNA. Induces death (Li, J .; Su, J .; Li, W .; Liu, W .; Altura, BT; Altura, BM: Peroxynitrite induces apoptosis in canine cerebral vascular muscle cells: possible relation to neurodegenerative diseases and strokes., Neurosci. Lett. 2003, 350 , 173-177.). This series of reactions leads to nerve cell damage, which results in intracellular dysfunction.
한편, 복숭아 나무는 Prunus종으로 중국에서 기원했고, 장미종의 Prunoideae속에 속하는 5-10 m 높이의 낙엽성 나무로, 잎은 7-15 cm 길이에 2-3cm 폭으로 피침형이다. 꽃은 잎이 나기 전 이른 봄에 피며, 2.5-3cm 반경 크기의 5장의 분홍색 꽃잎으로 되어 있다. 열매는 과즙이 많고, 적갈색의 계란모양으로 1.5-2 cm 크기의 비교적 큰 하나의 씨를 가지고 있으며 과육은 노랗거나 하얗고, 껍질은 변종에 따라 잔털로 덮여있거나 매끄럽다. 복숭아 잎은 전통적인 약재로서 관절염과 두통에 사용되어 왔으며(Oxford English Dictionary), 아직까지 신경세포의 보호 효능이 있다는 것은 보고된 바 없다.On the other hand, the peach tree is a Prunus species originated in China, and is a deciduous tree of 5-10 m height belonging to the genus Prunoideae, and the leaves are lanceolate 7-15 cm long and 2-3 cm wide. Flowers bloom in early spring before leaves and consist of 5 pink petals 2.5-3 cm in diameter. Fruits are juicy, reddish brown egg-shaped, with a relatively large seed, 1.5-2 cm in size, fleshy yellow or white, and its shell covered with fine hairs or smooth depending on the variety. Peach leaves have been used for arthritis and headaches as a traditional medicine ( Oxford English Dictionary ), and it has not been reported to protect neurons.
본 발명자들은 식용생물자원으로부터 여러 가지 생리활성을 갖는 미량소재에 대해 연구하던 중 복숭아 잎 추출물이 신경세포보호능을 나타냄을 확인하고 본 발명을 완성하였다.The present inventors have completed the present invention, confirming that the peach leaf extract exhibits neuronal cell protection while studying a micromaterial having various physiological activities from edible biological resources.
본 발명은 식용생물자원으로부터 신경세포 보호능을 나타내는 물질을 개발하여, 이를 포함하는 신경세포 보호용 조성물을 제공하는 것을 목적으로 한다. It is an object of the present invention to develop a substance that exhibits neuronal cell protection from edible biological resources and to provide a neuronal cell protective composition comprising the same.
또한, 본 발명은 상기 신경세포 보호 물질을 식용생물자원으로부터 정제하는 방법을 제공하는 것을 목적으로 한다.It is also an object of the present invention to provide a method for purifying the neuronal protective substance from edible biological resources.
본 발명은 복숭아 잎 추출물을 유효 성분으로 포함하는 신경세포 보호용 조성물을 제공한다.The present invention provides a nerve cell protective composition comprising a peach leaf extract as an active ingredient.
또한 본 발명은 상기 복숭아 잎 추출물 분획의 정제 방법을 제공한다.The present invention also provides a method for purifying the peach leaf extract fraction.
본 발명은 복숭아 잎 추출물의 신경세포 보호 용도를 제공한다. 따라서, 복숭아 잎 추출물을 유효 성분으로 포함하는 조성물은 신경세포 보호와 연관되는 뇌신경 질환, 뇌졸중, 뇌경색, 뇌색전, 허혈성 신경질환, 퇴행성 신경질환, 중풍, 알츠하이머병, 파킨슨 병, 치매, 헌팅턴병, 피크병, 크로이츠펠트-야콥병, 다발성 경화증, 허혈성 뇌질환, 간질, 루게릭병, 기억력 감퇴, 외상 또는 질환에 의한 신경세포 손상, 뇌진탕, 진행성 핵상마비, 다계통 위축증, 감람핵-뇌교-소뇌 위축증(OPCA), 샤이-드래거 증후군, 선초체-흑질 퇴행증, 근위축성 측색 경화증(ALS), 본태성 진전증, 피질-기저핵 퇴행증, 미만성 루이 소체 질환, 파킨슨-ALS-치매 복합증, 픽병 등의 다양한 질환을 효과적으로 예방 또는 치료하기 위해 사용될 수 있다. The present invention provides a neuronal protective use of the peach leaf extract. Therefore, the composition comprising the peach leaf extract as an active ingredient, cerebral neurological disease, stroke, cerebral infarction, cerebral embolism, ischemic neurological disease, degenerative neurological disease, stroke, Alzheimer's disease, Parkinson's disease, dementia, Huntington's disease, Peak disease associated with neuronal cell protection , Creutzfeldt-Jakob disease, multiple sclerosis, ischemic brain disease, epilepsy, Lou Gehrig's disease, memory loss, nerve cell damage caused by trauma or disease, concussion, progressive nuclear palsy, polypharyngeal atrophy, olive nucleus-brain-cerebellar atrophy (OPCA) Various diseases such as Shy-Dragger syndrome, stromal-black degeneration, Amyotrophic lateral sclerosis (ALS), essential tremor, cortical-basal ganglia degeneration, diffuse Lewis body disease, Parkinson-ALS-dementia complications, pick disease It can be used to effectively prevent or treat
본 발명은 복숭아 잎 추출물을 유효 성분으로 포함하는 신경세포 보호용 조성물을 제공한다.The present invention provides a nerve cell protective composition comprising a peach leaf extract as an active ingredient.
본 발명의 복숭아 잎 추출물의 제조시에는 건조 또는 미건조시킨 복숭아 잎 또는 이들의 혼합물을 사용할 수 있다. 추출의 효율성을 위해 복숭아 잎은 잘게 부수어 사용될 수 있다. 또한, 효과적인 신경세포 보호용 복숭아 잎 추출물을 얻기 위해, 복숭아 잎의 분쇄 전에 약 100℃의 높은 온도에서 약 5분간 블랜칭(blanching)을 수행하여 생체 세포내 효소를 불활성화시키는 과정을 거칠 수 있다. In the preparation of the peach leaf extract of the present invention, dried or undried peach leaves or mixtures thereof can be used. For the efficiency of extraction the peach leaves can be used by crushing. In addition, in order to obtain an effective neuronal protective peach leaf extract, it may be subjected to a process of incubating for about 5 minutes at a high temperature of about 100 ℃ before pulverizing the peach leaf to inactivate the enzyme in vivo cells.
복숭아 잎 추출물의 제조를 위해서는 복숭아 잎의 3 내지 10 배의 추출 용매를 사용하여 통상적인 추출 방법에 따라 추출할 수 있다. For the preparation of the peach leaf extract can be extracted according to a conventional extraction method using 3 to 10 times the extraction solvent of the peach leaf.
추출 용매로는 천연물 추출에서 널리 이용되고 있는 물, 유기 용매 또는 이들의 혼합 용매를 이용하여 추출될 수 있다. 상기 유기 용매로는 메탄올 또는 에탄올이 포함된다. 이 경우 메탄올 또는 에탄올은 물과 혼합하여 사용할 수 있으나, 활성 성분의 용이한 용출을 위해서는 물과 혼합하지 않고 사용할 수도 있다. 한 구체예에서, 상기 복숭아 잎 추출물은 메탄올 추출물일 수 있다.The extraction solvent may be extracted using water, an organic solvent, or a mixed solvent thereof which is widely used in natural product extraction. The organic solvent includes methanol or ethanol. In this case, methanol or ethanol may be mixed with water, but may be used without mixing with water for easy elution of the active ingredient. In one embodiment, the peach leaf extract may be a methanol extract.
상기 복숭아 잎 추출물은 1차 추출에서 사용된 유기 용매와는 극성이 다른 유기 용매를 사용하여 추가로 분획할 수 있다. 또한, 실리카겔 컬럼 크로마토그래피(silica gel column chromatography), 박층 크로마토그래피(thin layer chromatography), 고성능 액체 크로마토그래피(high performance liquid chromatography) 등과 같은 다양한 크로마토그래피를 이용하여 추가로 정제된 분획을 얻을 수도 있다. 본 발명에 있어서, '복숭아 잎 추출물'에는 이와 같이 추출, 분획 또는 정제의 각 단계에서 얻어지는 모든 추출액, 분획 및 정제물, 그들의 희석액, 농축액 또는 건조물을 포함한다. The peach leaf extract may be further fractionated using an organic solvent that is different in polarity from the organic solvent used in the first extraction. In addition, fractions further purified may be obtained using various chromatography such as silica gel column chromatography, thin layer chromatography, high performance liquid chromatography, and the like. In the present invention, the peach leaf extract includes all the extracts, fractions and purified products obtained in each step of extraction, fractionation or purification as described above, their dilutions, concentrates or dried products.
따라서, 본 발명의 한 구체예에서, 상기 복숭아 잎 추출물은 복숭아 잎을 물, 유기 용매 또는 이들의 혼합용매로 추출하고, 그 잔사를 헥산, 클로로포름 및 에틸아세테이트을 이용하여 순차적으로 분획하고 감압 농축한 후 건조하여 얻은 복숭아 잎 추출물 분획일 수 있다. 한 측면에서, 상기 복숭아 잎 추출물 분획은 복숭아 잎을 메탄올로 추출하고 그 잔사를 헥산, 클로로포름 및 에틸아세테이트를 이용하여 순차적으로 분획하여 얻은 에틸아세테이트 분획일 수 있다. Therefore, in one embodiment of the present invention, the peach leaf extract is extracted with peach leaves with water, an organic solvent or a mixed solvent, the residue is sequentially fractionated using hexane, chloroform and ethyl acetate and concentrated under reduced pressure It may be a peach leaf extract fraction obtained by drying. In one aspect, the peach leaf extract fraction may be an ethyl acetate fraction obtained by sequentially extracting the peach leaves with methanol and the residues sequentially using hexane, chloroform and ethyl acetate.
본 발명의 다른 구체예에서, 상기 복숭아 잎 추출물은 복숭아 잎을 물, 유기 용매 또는 이들의 혼합용매로 추출하고, 그 잔사를 헥산, 클로로포럼 및 에틸아세테이트을 이용하여 순차적으로 분획하고 감압 농축한 후 건조하여 얻은 복숭아 잎 추출물 분획에 대해 클로로포름과 메탄올의 혼합 용매를 전개용매로 사용하는 실리카겔 컬럼 크로마토그래피(silica gel column chromatography)를 수행하여 얻은 분획 중 클로로포름 : 메탄올 = 90:10 ~ 70:30의 전개용매조건에서 얻은 복숭아 잎 추출물 분획일 수 있다. In another embodiment of the present invention, the peach leaf extract is extracted with peach leaves with water, an organic solvent or a mixed solvent thereof, the residue is sequentially fractionated using hexane, chloroforum and ethyl acetate, concentrated under reduced pressure and dried Chloroform in the fraction obtained by silica gel column chromatography using a mixed solvent of chloroform and methanol as a developing solvent with respect to the peach leaf extract fraction obtained by using the solvent as the developing solvent of methanol: 90:10 to 70:30. It may be a peach leaf extract fraction obtained under the conditions.
본 발명의 또 다른 구체예에서, 상기 복숭아 잎 추출물은 복숭아 잎을 물, 유기 용매 또는 이들의 혼합용매로 추출하고, 그 잔사를 헥산, 클로로포럼 및 에틸아세테이트을 이용하여 순차적으로 분획하고 감압 농축한 후 건조하여 얻은 복숭아 잎 추출물 분획에 대해 클로로포름과 메탄올의 혼합 용매를 전개용매로 사용하는 실리카겔 컬럼 크로마토그래피(silica gel column chromatography)를 수행하여 얻은 분획 중 클로로포름 : 메탄올 = 90:10 ~ 70:30의 전개용매조건에서 복숭아 잎 추출물 분획을 얻고, 상기 수득한 복숭아 잎 추출물 분획에 대해 TLC(thin layer chromatography) 또는 HPLC(high performance liquid chromatography)를 수행하여 추가로 정제된 복숭아 잎 추출물 분획일 수 있다. In another embodiment of the present invention, the peach leaf extract is extracted with peach leaves with water, an organic solvent or a mixed solvent thereof, the residue is sequentially fractionated using hexane, chloroforum and ethyl acetate and concentrated under reduced pressure Chloroform in the fraction obtained from the dried peach leaf extract fraction obtained by performing silica gel column chromatography using a mixed solvent of chloroform and methanol as a developing solvent: development of methanol: 90:10 to 70:30 The peach leaf extract fraction may be obtained under solvent conditions, and the peach leaf extract fraction may be further purified by performing thin layer chromatography (TLC) or high performance liquid chromatography (HPLC).
본 발명은 또한 The invention also
1) 복숭아 잎을 물, 유기 용매 또는 이들의 혼합용매로 추출하고, 그 잔사를 헥산, 클로로포럼 및 에틸아세테이트을 이용하여 순차적으로 분획하고 감압 농축한 후 건조하여 복숭아 잎 추출물 분획을 얻는 단계;1) extracting the peach leaves with water, an organic solvent or a mixed solvent thereof, and fractions were extracted sequentially with hexane, chloroforum and ethyl acetate, concentrated under reduced pressure and dried to obtain a peach leaf extract fraction;
2) 상기 단계 1로부터 얻은 복숭아 잎 추출물 분획에 대해 클로로포름과 메탄올의 혼합 용매를 전개용매로 사용하는 실리카겔 컬럼 크로마토그래피(silica gel column chromatography)를 수행하여 얻은 분획 중 클로로포름 : 메탄올 = 90:10 ~ 70:30의 전개용매조건에서 복숭아 잎 추출물 분획을 얻는 단계; 및2) Chloroform in the fraction obtained by silica gel column chromatography using a mixed solvent of chloroform and methanol as a developing solvent for the peach leaf extract fraction obtained in step 1: methanol = 90:10 to 70 Obtaining a peach leaf extract fraction under a developing solvent condition of: 30; And
3) 상기 단계 2로부터 수득한 복숭아 잎 추출물 분획에 대해 TLC(thin layer chromatography) 및 HPLC(high performance liquid chromatography)를 수행하여 신 경세포 보호 활성을 나타내는 복숭아 잎 추출물 분획을 얻는 단계를 포함하는3) performing a thin layer chromatography (TLC) and high performance liquid chromatography (HPLC) on the peach leaf extract fraction obtained from step 2 to obtain a peach leaf extract fraction exhibiting neuronal cell protective activity.
신경세포 보호용 복숭아 잎 추출물 분획의 정제 방법을 제공한다.Provided is a method for purifying the peach leaf extract fraction for protecting nerve cells.
본 발명의 하기 실시예에서는, 복숭아 잎을 100% 메탄올로 추출하여 얻은 잔사(이하 실시예에서, 'CM'으로 표현됨)를, 헥산, 클로로포름, 에틸아세테이트의 순으로 분획하고 감압 건조하여 복숭아 잎 추출물 분획(이하 실시예에서 'MH', 'MC', 'ME 및 'MM'으로 표현됨)을 제조하였다. 또한, 상기 복숭아 잎 추출물 분획 중 에틸아세테이트 분획(ME)을 추가로 분획하고 정제하였다. 이러한 과정을 통해 얻은 본 발명의 복숭아 잎 추출물은 퍼옥시나이트라이트 발생시약인 SIN-1(3-morpholinosydninimine hydrochloride )만을 처리한 양성 대조군과 비교할 때, 최대 약 8배까지 신경세포의 생존율을 높이는 보호 효과를 나타낸다.In the following examples of the present invention, the residue obtained by extracting peach leaves with 100% methanol (hereinafter referred to as 'CM'), fractions in the order of hexane, chloroform, ethyl acetate and dried under reduced pressure to extract peach leaves Fractions (hereinafter referred to as' MH ',' MC ',' ME and 'MM' in the Examples) were prepared. In addition, the ethyl acetate fraction (ME) in the peach leaf extract fractions were further fractionated and purified. The peach leaf extract of the present invention obtained through this process has a protective effect of increasing the survival rate of neurons up to about 8 times as compared with the positive control treated with only SIN-1 (3-morpholinosydninimine hydrochloride), a peroxynitrite generating reagent. Indicates.
따라서 본 발명의 복숭아 잎 추출물은 신경세포 보호용 조성물의 유효 성분으로 포함될 수 있다. Therefore, the peach leaf extract of the present invention may be included as an active ingredient of the neuronal protective composition.
본 발명의 신경세포 보호용 조성물은 신경세포의 보호와 관련된 질환의 예방 또는 치료용 조성물로서 사용될 수 있다. 신경세포의 보호와 관련된 질환은 이에 제한되는 것은 아니나, 예를 들어, 뇌신경 질환, 뇌졸중, 뇌경색, 뇌색전, 허혈성 신경질환, 퇴행성 신경질환, 중풍, 알츠하이머병, 파킨슨 병, 치매, 헌팅턴병, 피크병, 크로이츠펠트-야콥병, 다발성 경화증, 허혈성 뇌질환, 간질, 루게릭병, 기억력 감퇴, 외상 또는 질환에 의한 신경세포 손상, 뇌진탕, 진행성 핵상마비, 다계통 위축증, 감람핵-뇌교-소뇌 위축증(OPCA), 샤이-드래거 증후군, 선초체-흑질 퇴행증, 근위축성 측색 경화증(ALS), 본태성 진전증, 피질-기저핵 퇴행증, 미만성 루이 소체 질환, 파킨슨-ALS-치매 복합증, 픽병 등으로 구성되는 군으로부터 선택되는 질환일 수 있다. The neuronal protective composition of the present invention can be used as a composition for the prevention or treatment of diseases related to the protection of neurons. Diseases related to the protection of neurons are not limited to, for example, cranial nerve disease, stroke, cerebral infarction, cerebral embolism, ischemic neurological disease, degenerative neurological disease, stroke, Alzheimer's disease, Parkinson's disease, dementia, Huntington's disease, Peak disease, Creutzfeldt-Jakob disease, multiple sclerosis, ischemic brain disease, epilepsy, Lou Gehrig's disease, memory loss, nerve cell damage caused by trauma or disease, concussion, progressive nuclear palsy, polypharyngeal atrophy, olive nucleus-brain-cerebellar atrophy (OPCA), Group consisting of Shy-Dragger syndrome, stromal-black degeneration, Amyotrophic lateral sclerosis (ALS), essential tremor, cortical-basal ganglia degeneration, diffuse Lewis body disease, Parkinson-ALS-dementia complications, pick disease It may be a disease selected from.
상기 조성물은 본 발명의 복숭아 잎 추출물뿐만 아니라 기존에 공지된 신경세포 보호제와 함께 사용될 수 있다. The composition can be used with a peach leaf extract of the present invention as well as a neuroprotective agent known in the art.
본 발명에 따른 신경세포 보호용 조성물은 약제학적 조성물 또는 식품 조성물일 수 있다. The neuronal cell protective composition according to the present invention may be a pharmaceutical composition or a food composition.
본 발명의 복숭아 잎 추출물을 유효 성분으로 포함하는 약제학적 조성물은 상기 유효 성분 이외에 약제학적으로 적합하고 생리학적으로 허용되는 보조제를 사용하여 제조될 수 있으며, 상기 보조제로는 부형제, 붕해제, 감미제, 결합제, 피복제, 팽창제, 윤활제, 활택제 또는 향미제 등을 사용할 수 있다.A pharmaceutical composition comprising the peach leaf extract of the present invention as an active ingredient may be prepared using a pharmaceutically acceptable and physiologically acceptable adjuvant in addition to the active ingredient, and the adjuvant may include excipients, disintegrants, sweeteners, Binders, coatings, swelling agents, lubricants, lubricants, flavoring agents, and the like can be used.
상기 약제학적 조성물은 투여를 위해서 상기 기재한 유효 성분 이외에 추가로 약제학적으로 허용 가능한 담체를 1종 이상 포함하여 약제학적 조성물로 바람직하게 제제화할 수 있다. The pharmaceutical composition may be preferably formulated into a pharmaceutical composition comprising one or more pharmaceutically acceptable carriers in addition to the active ingredient described above for administration.
상기 약제학적 조성물의 제제 형태는 과립제, 산제, 정제, 피복정, 캡슐제, 좌제, 액제, 시럽, 즙, 현탁제, 유제, 점적제 또는 주사 가능한 액제 등이 될 수 있다. 예를 들어, 정제 또는 캡슐제의 형태로의 제제화를 위해, 유효 성분은 에탄올, 글리세롤, 물 등과 같은 경구, 무독성의 약제학적으로 허용 가능한 불활성 담체와 결합될 수 있다. 또한, 원하거나 필요한 경우, 적합한 결합제, 윤활제, 붕해제 및 발색제 또한 혼합물로 포함될 수 있다. 적합한 결합제는 이에 제한되는 것은 아니나, 녹말, 젤라틴, 글루코스 또는 베타-락토오스와 같은 천연 당, 옥수수 감미 제, 아카시아, 트래커캔스 또는 소듐올레이트와 같은 천연 및 합성 검, 소듐 스테아레이트, 마그네슘 스테아레이트, 소듐 벤조에이트, 소듐 아세테이트, 소듐 클로라이드 등을 포함한다. 붕해제는 이에 제한되는 것은 아니나, 녹말, 메틸 셀룰로스, 아가, 벤토니트, 잔탄 검 등을 포함한다. 액상 용액으로 제제화되는 조성물에 있어서 허용 가능한 약제학적 담체로는, 멸균 및 생체에 적합한 것으로서, 식염수, 멸균수, 링거액, 완충 식염수, 알부민 주사용액, 덱스트로즈 용액, 말토 덱스트린 용액, 글리세롤, 에탄올 및 이들 성분 중 1 성분 이상을 혼합하여 사용할 수 있으며, 필요에 따라 항산화제, 완충액, 정균제 등 다른 통상의 첨가제를 첨가할 수 있다. 또한 희석제, 분산제, 계면활성제, 결합제 및 윤활제를 부가적으로 첨가하여 수용액, 현탁액, 유탁액 등과 같은 주사용 제형, 환약, 캡슐, 과립 또는 정제로 제제화할 수 있다. 더 나아가 해당분야의 적절한 방법으로 Remington's Pharmaceutical Science, Mack Publishing Company, Easton PA에 개시되어 있는 방법을 이용하여 각 질환에 따라 또는 성분에 따라 바람직하게 제제화 할 수 있다. Formulation forms of the pharmaceutical composition may be granules, powders, tablets, coated tablets, capsules, suppositories, solutions, syrups, juices, suspensions, emulsions, drops or injectable solutions. For example, for formulation in the form of tablets or capsules, the active ingredient may be combined with an oral, nontoxic, pharmaceutically acceptable inert carrier such as ethanol, glycerol, water and the like. In addition, if desired or necessary, suitable binders, lubricants, disintegrants and coloring agents may also be included in the mixture. Suitable binders include but are not limited to natural sugars such as starch, gelatin, glucose or beta-lactose, natural and synthetic gums such as corn sweeteners, acacia, trackercance or sodium oleate, sodium stearate, magnesium stearate, Sodium benzoate, sodium acetate, sodium chloride, and the like. Disintegrants include, but are not limited to, starch, methyl cellulose, agar, bentonite, xanthan gum, and the like. Acceptable pharmaceutical carriers in compositions formulated in liquid solutions are sterile and physiologically compatible, including saline, sterile water, Ringer's solution, buffered saline, albumin injectable solutions, dextrose solution, maltodextrin solution, glycerol, ethanol and One or more of these components may be mixed and used, and other conventional additives such as antioxidants, buffers and bacteriostatic agents may be added as necessary. In addition, diluents, dispersants, surfactants, binders, and lubricants may be additionally added to formulate into injectable solutions, pills, capsules, granules or tablets such as aqueous solutions, suspensions, emulsions and the like. Furthermore, the method disclosed in Remington's Pharmaceutical Science, Mack Publishing Company, Easton PA can be formulated according to each disease or component, as appropriate in the art.
또한, 본 발명은 상기 복숭아 잎 추출물을 포함하는 신경세포 보호용 식품 조성물을 제공한다.The present invention also provides a food composition for nerve cell protection comprising the peach leaf extract.
본 발명에 따른 식품 조성물은 상기 약제학적 조성물과 동일한 방식으로 제제화되어 기능성 식품으로 이용하거나, 각종 식품에 첨가할 수 있다. 본 발명의 조성물을 첨가할 수 있는 식품으로는 예를 들어, 음료류, 육류, 초코렛, 식품류, 과자류, 피자, 라면, 기타 면류, 껌류, 아이스크림류, 알코올 음료류, 비타민 복합제, 건강보조식품류 등이 있다.The food composition according to the present invention may be formulated in the same manner as the pharmaceutical composition, used as a functional food, or added to various foods. Foods to which the composition of the present invention can be added include, for example, beverages, meat, chocolate, foods, confectionery, pizza, ramen, other noodles, gums, ice creams, alcoholic beverages, vitamin complexes, and health supplements. .
본 발명은 상기 신경세포 보호용 조성물을 포함하는 건강기능식품을 제공한다.The present invention provides a health functional food comprising the neuron protective composition.
본 발명은 또한 신경세포 보호용 의약 또는 식품의 제조를 위한 상기 복숭아 잎 추출물을 유효 성분으로 포함하는 조성물의 용도를 제공한다. 상기한 복숭아 잎 추출물을 유효 성분으로 포함하는 본 발명의 조성물은 신경세포 보호와 관련된 질환의 예방 또는 치료용 의약 또는 식품의 제조를 위한 용도로 이용될 수 있다.The present invention also provides the use of a composition comprising the peach leaf extract as an active ingredient for the manufacture of a medicament or food for protecting neurons. The composition of the present invention comprising the peach leaf extract as an active ingredient can be used for the manufacture of a medicament or food for the prevention or treatment of diseases related to neuronal cell protection.
또한 본 발명은 포유동물에게 치료상 유효량의 복숭아 잎 추출물을 투여하는 것을 포함하는 신경세포 보호 방법, 또는 신경세포 보호과 관련된 질환의 예방 또는 치료 방법을 제공한다.The present invention also provides a method of neuronal cell protection comprising administering to a mammal a therapeutically effective amount of a peach leaf extract, or a method of preventing or treating a disease associated with neuronal cell protection.
여기에서 사용된 용어 "포유동물"은 치료, 관찰 또는 실험의 대상인 포유동물을 말하며, 바람직하게는 인간을 말한다. As used herein, the term "mammal" refers to a mammal that is the subject of treatment, observation or experimentation, preferably human.
여기에서 사용된 용어 "치료상 유효량"은 연구자, 수의사, 의사 또는 기타 임상의에 의해 생각되는 조직계, 동물 또는 인간에서 생물학적 또는 의학적 반응을 유도하는 유효 성분 또는 약학적 조성물의 양을 의미하는 것으로, 이는 치료되는 질환 또는 장애의 증상의 완화를 유도하는 양을 포함한다. 본 발명의 유효 성분에 대한 치료상 유효 투여량 및 투여횟수는 원하는 효과에 따라 변화될 것임은 당업자에게 자명하다. 그러므로, 투여될 최적의 투여량은 당업자에 의해 쉽게 결정될 수 있으며, 질환의 종류, 질환의 중증도, 조성물에 함유된 유효성분 및 다른 성분의 함량, 제형의 종류, 및 환자의 연령, 체중, 일반 건강 상태, 성별 및 식이, 투여 시간, 투여 경로 및 조성물의 분비율, 치료기간, 동시 사용되는 약물을 비롯한 다양한 인자에 따라 조절될 수 있다. 본 발명의 치료방법에 있어서, 성인의 경우, 본 발명의 복숭아 잎 추출물을 1일 1회 내지 수회 투여시, 1㎎/kg~250㎎/kg의 용량으로 투여하는 것이 바람직하다. As used herein, the term “therapeutically effective amount” means an amount of an active ingredient or pharmaceutical composition that induces a biological or medical response in a tissue system, animal or human, as contemplated by a researcher, veterinarian, doctor or other clinician, This includes amounts that induce alleviation of the symptoms of the disease or disorder being treated. It will be apparent to those skilled in the art that the therapeutically effective dosages and frequency of administrations for the active ingredients of the present invention will vary depending on the desired effect. Therefore, the optimal dosage to be administered can be readily determined by one skilled in the art and includes the type of disease, the severity of the disease, the amount of active ingredients and other ingredients contained in the composition, the type of formulation, and the age, weight, general health of the patient. It can be adjusted according to various factors, including the condition, sex and diet, time of administration, route of administration and rate of composition, duration of treatment, and drugs used simultaneously. In the treatment method of the present invention, for adults, when the peach leaf extract of the present invention is administered once to several times a day, it is preferable to administer at a dose of 1 mg / kg to 250 mg / kg.
본 발명의 치료방법에서 본 발명의 복숭아 잎 추출물을 유효 성분으로 포함하는 조성물은 경구, 직장, 정맥내, 동맥내, 복강내, 근육내, 흉골내, 경피, 국소, 안구내 또는 피내 경로를 통해 통상적인 방식으로 투여할 수 있다. In the treatment method of the present invention, the composition comprising the peach leaf extract of the present invention as an active ingredient may be administered by oral, rectal, intravenous, intraarterial, intraperitoneal, intramuscular, intrasternal, transdermal, topical, intraocular or intradermal routes. It may be administered in a conventional manner.
본 발명의 이점 및 특징, 그리고 그것들을 달성하는 방법은 상세하게 후술되어 있는 실시예들을 참조하면 명확해질 것이다. 그러나 본 발명은 이하에서 개시되는 실시예들에 한정되는 것이 아니라 서로 다른 다양한 형태로 구현될 것이며, 단지 본 실시예들은 본 발명의 개시가 완전하도록 하고, 본 발명이 속하는 기술 분야에서 통상의 지식을 가진 자에게 발명의 범주를 완전하게 알려주기 위해 제공되는 것이며, 본 발명은 청구항의 범주에 의해 정의될 뿐이다.Advantages and features of the present invention and methods for achieving them will be apparent with reference to the embodiments described below in detail. However, the present invention is not limited to the embodiments disclosed below, but may be implemented in various forms. It is provided to fully convey the scope of the invention to those skilled in the art, and the present invention is defined only by the scope of the claims.
[실시예]EXAMPLE
실시예 1 : 복숭아 잎 추출물 및 복숭아잎 추출물 분획의 제조 및 이들의 신경세포 보호 활성 확인Example 1 Preparation of Peach Leaf Extract and Peach Leaf Extract Fractions and Confirmation of Their Neuronal Protective Activity
복숭아 잎을 100℃에서 5분간 블랜칭(blanching)하여 생체세포내 효소를 불활성화시키고 핸드믹서로 곱게 분쇄한 후, 실온에서 시료의 5배의 100% 메탄올(v/v)로 24시간 동안 정치하여 추출하고, 그 추출물을 감압농축하여 건조시켰 다('CM'). 상기 건조물을 다시 증류수 1리터에 녹여 같은 양의 헥산, 클로로포름, 에틸아세테이트 순으로 각각 분획깔대기를 사용하여 분획하고('MH', 'MC', 'ME), 남은 것을 메탄올에 녹여 여과포로 여과하고 잔사를 감압농축한 후 건조하여 추출물을 얻었다('MM'). 도 1은 본 발명의 실시예에 따른 복숭아 잎의 메탄올 추출 및 추출물의 유기용매 분획 단계를 보여주는 과정도이다. Peach leaves were incubated at 100 ° C. for 5 minutes to inactivate enzymes in living cells and finely pulverized with a hand mixer, and then allowed to stand for 24 hours with 5
복숭아 잎 추출물과 각 분획물의 신경세포 보호 활성을 확인하기 위하여 퍼옥시나이트라이트의 발생시약인 SIN-1과 섬유아세포종(neuroblastoma) 세포주인 SH-SY5Y 세포를 이용한 인 비트로 어세이계를 확립하여 세포 생존율을 측정하였다. 먼저, SH-SY5Y 세포를 96 웰 디쉬에 3 X104 세포씩 seeding한 후, 1 ㎎/㎖의 extracts library시료와 250 μM SIN-1를 24시간 동안 처리하였다. Formazan 형성을 측정하기 위하여 5 mg/ml 3-(4,5-dimethylthiazoyl-2-yl)-2,5-diphenyltetrazolium bromide (MTT) solution 25 ul를 가하고 3시간 동안 반응시킨 후 배지를 제거하였다. 생성된 formazan을 DMSO에 녹여 A540을 측정하여, 생존률을 측정하였다. In order to confirm the neuroprotective activity of peach leaf extract and each fraction, we established an in vitro assay system using SIN-1, a generation agent of peroxynitrite, and SH-SY5Y cell, a fibroblastoma cell line, to improve cell viability. Measured. First, SH-SY5Y cells were seeded by 3 X10 4 cells in 96 well dishes, and then treated with 1 mg / mL extracts library sample and 250 μM SIN-1 for 24 hours. To measure formazan formation, 25 mg of 5 mg / ml 3- (4,5-dimethylthiazoyl-2-yl) -2,5-diphenyltetrazolium bromide (MTT) solution was added and reacted for 3 hours, and then the medium was removed. The resulting formazan was dissolved in DMSO to measure A 540 and survival rate was measured.
상기와 같이 분획에 따른 신경세포 보호활성을 측정한 결과, 처음 메탄올 추출물(CM)에서도 높은 활성을 나타내었으나, 에틸아세테이트 분획(ME)에서 가장 높은 활성을 나타내는 것을 확인하였다. 도 2는 도 1의 각 단계 분획물의 신경세포 보호활성 결과를 나타낸 도표이다.As a result of measuring the neuronal protective activity according to the fraction as described above, the first showed a high activity even in the methanol extract (CM), it was confirmed that the highest activity in the ethyl acetate fraction (ME). 2 is a graph showing the results of neuronal cell protective activity of each step fraction of FIG.
실시예 2 : 크로마토그래피를 이용한 복숭아 잎 추출물 분획의 정제 및 복숭아 잎 추출물 분획의 신경세포 보호 활성 확인Example 2 Purification of Peach Leaf Extract Fraction by Chromatography and Confirmation of Neuronal Protective Activity of Peach Leaf Extract Fraction
크로마토그래피를 이용하여 실시예 2를 통해 얻은 복숭아 잎 에틸아세테이트 분획물(ME)을 정제하였다. 클로로포름으로 활성화된 실리카겔 60 컬럼에 시료인 에틸아세테이트 분획(ME)를 로딩하고 클로로포름과 메탄올(CHCl3 : MeOH = 100 : 0 ~ 0 : 100) 혼합용액으로 5 bed volume씩 전개한 후, 퍼옥시나이트라이트에 대한 신경세포 보호활성을 검토하였으며, 최종적으로 클로로포름-메탄올 80: 20 첫번째 분획에서 신경세포 보호활성을 갖는 소분획을 분리하였다(CME3a). The peach leaf ethyl acetate fraction (ME) obtained through Example 2 was purified using chromatography. Ethyl acetate fraction (ME) was loaded onto a
위와 같이 분리한 신경세포 보호활성이 높은 용출분획(CME3a)에 대해 TLC을 수행하였다. TLC에서는 에틸아세테이트 / 포름산 / D.W (65:15:20, v/v/v)을 전개용매로 사용하여 활성분획을 분리하였다. TLC was performed on the elution fraction (CME3a) having high neuronal cell protective activity isolated as described above. In TLC, the active fractions were separated using ethyl acetate / formic acid / D.W (65:15:20, v / v / v) as the developing solvent.
TLC로부터 수득한 높은 활성분획(CME3aβ)을 모아 HPLC (u-Bondapak C18 (4.5 × 150 mm)를 사용하여 H2O : 아세토니트릴 = 100 : 0 ~ 40 : 60의 용매조건과 1 ml/min의 유속으로 용출시키고, 활성분획(CME3aβ-Ⅲ)만을 농축한 후 활성분획을 동일한 조건에서 HPLC를 실시한 결과 좌우 대칭의 단일 peak를 보임으로써 비교적 정제도 높게 물질을 정제할 수 있었다. 도 3은 실시예 1로부터 수득한 복숭아 잎 메탄올 추출물의 에틸아세테이트 분획(CME)의 정제단계를 보여주는 과정도이고, 도 4는 도 3의 분리물질의 정제도를 보여주는 HPLC 크로마토그램이다.The high activity fraction (CME3aβ) obtained from TLC was collected using HPLC (u-Bondapak C 18 (4.5 × 150 mm) and H 2 O: acetonitrile = 100: 0 ~ 40: 60 solvent conditions and 1 ml / min After eluting at a flow rate of and concentrating only the active fraction (CME3aβ-III), the active fraction was subjected to HPLC under the same conditions. Process diagram showing the purification step of the ethyl acetate fraction (CME) of the peach leaf methanol extract obtained from Example 1, Figure 4 is an HPLC chromatogram showing the purification degree of the separation material of FIG.
실시예 3 : 정제 단계별 신경세포 보호 활성 평가Example 3 Evaluation of Neuronal Protective Activity According to Purification
실시예 1의 방법을 이용하여, 복숭아 잎으로부터 분리한 정제물질의 정제 단계별 신경세포 보호 활성을 측정하였다. 도 2는 정제단계물질의 저해활성을 시험한 결과를 나타낸 도표이다. 정제단계가 진행될수록 더 많은 저해활성을 나타내었으며, 최종 HPLC 정제물(CME3aβ-Ⅲ)은 0.2 mg/ml의 농도에서 가장 높은 저해활성을 보였다.Using the method of Example 1, the neuronal protective activity of each of the purified substances separated from the peach leaves was measured. Figure 2 is a chart showing the results of testing the inhibitory activity of the purification step material. As the purification step proceeded, more inhibitory activity was shown, and the final HPLC purified product (CME3aβ-III) showed the highest inhibitory activity at the concentration of 0.2 mg / ml.
도 1은 본 발명의 실시예에 따른 복숭아 잎의 메탄올 추출 및 추출물의 유기용매 분획 단계를 보여주는 과정도이다. 1 is a process chart showing the methanol extraction of the peach leaf and the organic solvent fraction step of the extract according to an embodiment of the present invention.
도 2는 도 1의 각 단계 분획물의 신경세포 보호활성 결과를 나타낸 도표이다.2 is a graph showing the results of neuronal cell protective activity of each step fraction of FIG.
도 3은 복숭아 잎의 메탄올 추출물(CM)을 유기 용매를 이용하여 추가로 정제하여 얻은 복숭아 잎 메탄올 추출물-메탄올 분획(CM-M)의 신경세포 보호 활성을 보여주는 그래프이다.Figure 3 is a graph showing the neuronal protective activity of the peach leaf methanol extract (CM-M) obtained by further purification of the methanol extract (CM) of the peach leaf using an organic solvent.
도 3은 실시예 1로부터 수득한 복숭아 잎 메탄올 추출물의 에틸아세테이트 분획(CME)의 정제단계를 보여주는 과정도이다.Figure 3 is a process showing the purification step of the ethyl acetate fraction (CME) of the peach leaf methanol extract obtained from Example 1.
도 4는 도 3의 분리물질의 정제도를 보여주는 HPLC 크로마토그램이다.FIG. 4 is an HPLC chromatogram showing purification of the separation material of FIG. 3.
도 5는 복숭아 잎 추출물 분획의 정제 단계별 신경세포 보호 활성을 보여주는 그래프이다.5 is a graph showing the neuronal protective activity according to the purification step of the peach leaf extract fraction.
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US8871716B2 (en) | 2010-10-08 | 2014-10-28 | Korea Advanced Institute Of Science And Technology | Use of antimicrobial peptides in regeneration of skin cells |
US9034916B2 (en) | 2011-04-06 | 2015-05-19 | Korea Research Institute Of Bioscience And Biotechnology | Pharmaceutical composition for the prevention or treatment of a neurodegenerative disease, comprising a Daphne genkwa extract or a compound isolated therefrom |
US9114155B2 (en) | 2011-04-06 | 2015-08-25 | Korea Research Institute Of Bioscience And Biotechnology | Composition containing jetbead extracts |
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US8871716B2 (en) | 2010-10-08 | 2014-10-28 | Korea Advanced Institute Of Science And Technology | Use of antimicrobial peptides in regeneration of skin cells |
US9034916B2 (en) | 2011-04-06 | 2015-05-19 | Korea Research Institute Of Bioscience And Biotechnology | Pharmaceutical composition for the prevention or treatment of a neurodegenerative disease, comprising a Daphne genkwa extract or a compound isolated therefrom |
US9114155B2 (en) | 2011-04-06 | 2015-08-25 | Korea Research Institute Of Bioscience And Biotechnology | Composition containing jetbead extracts |
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