KR20150113434A - A composition comprising the extract of ginseng seed for protecting brain cells and preventing, improving and treating depression - Google Patents
A composition comprising the extract of ginseng seed for protecting brain cells and preventing, improving and treating depression Download PDFInfo
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- KR20150113434A KR20150113434A KR1020140036964A KR20140036964A KR20150113434A KR 20150113434 A KR20150113434 A KR 20150113434A KR 1020140036964 A KR1020140036964 A KR 1020140036964A KR 20140036964 A KR20140036964 A KR 20140036964A KR 20150113434 A KR20150113434 A KR 20150113434A
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- extract
- ginseng seed
- ginseng
- depression
- seed extract
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Classifications
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- A—HUMAN NECESSITIES
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- 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)
- A61K36/25—Araliaceae (Ginseng family), e.g. ivy, aralia, schefflera or tetrapanax
- A61K36/258—Panax (ginseng)
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
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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
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- A—HUMAN NECESSITIES
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- 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
- A61K2236/35—Extraction with lipophilic solvents, e.g. Hexane or petrol ether
Abstract
Description
본 발명은 인삼씨 추출물의 뇌신경세포 보호 및 우울증의 예방, 개선 및 치료를 위한 신규 용도에 관한 것이다.The present invention relates to a new use of ginseng seed extract for the prevention of neuronal cell protection and prevention, improvement and treatment of depression.
우울증 (depression)은 ‘마음의 감기’라도 일컬어지며, 인간의 모든 질병 중 자살율이 가장 높은 질환으로, 한사람이 평생 살아가면서 우울증에 걸릴 확률은 10-15% 로 어느 정신질환보다도 이환율이 높은 것으로 알려져 있다. Depression is also referred to as a "cold of the mind" and is the highest suicide rate among all human illnesses. It is known that a person has a higher morbidity rate than any mental illness, have.
우울증 유발 원인은 명확히 밝혀지지 않았으며, 최근 들어 다양한 분자 기전의 연구를 통하여 그 원인이 조금씩 밝혀 지고 있는데, 한가지의 단독적 원인이 아니라 여러 가지 기전들이 작용하여 우울증이 유발되는 것으로 알려지고 있다.The cause of depression has not been clarified. Recently, various molecular mechanisms have been found to cause the depression. It is known that depression is triggered by various mechanisms, not by a single cause.
우선 우울증에는 유전적 혹은 생물학적 소인이 내재하며 이는 스트레스에 의해 유발되는 것으로 알려져 있다. 스트레스는 시상하부의 실방핵(paraventricular nucleus: PVN)에서 corticotropin releasing factor(CRF) mRNA 발현을 증가시키며, 편도체에서는 glucocorticoid 수용체 발현을 증가시키며 우울증 환자들의 상당수에서 이와 같은 HPA axis의 이상이 발견되며, 이로 인한 장기적 우울증이 유발되는 것으로 밝혀졌다. First, depression is inherited by genetic or biological markers, which are known to be caused by stress. Stress increases the expression of corticotropin releasing factor (CRF) mRNA in the paraventricular nucleus (PVN) of the hypothalamus, increases glucocorticoid receptor expression in amygdala, and many of these patients have abnormal HPA axis. Term depression.
다음으로는 최근 스트레스와 우울증에 대한 연구들이 해마(hippocampus)를 중심으로 이루어지고 있는데. 스트레스 후에 해마가 위축되거나 해마 CA3 부위의 pyramidal neuron이 감소하는 등 형태학적 변화가 초래됨. 뇌 영상연구에서도 우울증 혹은 외상후 스트레스장애 환자들에게서 해마의 용적이 감소되어 있음이 관찰됨. 해마의 위축과 신경세포의 소실은 우울증 혹은 외상후 스트레스장애의 정신병리와 관련이 있을 것으로 발표 되었다.Next, recent studies on stress and depression are centered on the hippocampus. After stress, hippocampal atrophy or pyramidal neuron in hippocampal CA3 region is decreased. Brain imaging studies have also shown that hippocampus volume is reduced in patients with depression or posttraumatic stress disorder. The atrophy of the hippocampus and loss of neurons were reported to be related to the psychopathology of depression or posttraumatic stress disorder.
또한 항 우울제들이 스트레스에 의해 유발되는 해마 신경세포의 형태학적 변화 혹은 신경세포의 소실을 역전시킬 것이라는 기대는 이들이 해마에서 brain-derived neurotrophic factor (BDNF)의 발현을 촉진시킨다는 사실이 알려지면서 증폭되고 있는 상황이다. BDNF는 주로 뇌의 발달기에 신경세포의 분화나 생존에 관여한다고 알려져 있으며, 실제 항우울제 장기처치는 스트레스에 의해 유발된 신경세포돌기들의 위축을 회복시키는 것으로 밝혀지고 있다. In addition, the anticipation that antidepressants will reverse the stress-induced morphological changes of hippocampal neurons or the loss of neurons is amplified as they are known to promote brain-derived neurotrophic factor (BDNF) expression in the hippocampus It is a situation. BDNF is known to be involved mainly in neuronal differentiation and survival in the developmental stage of the brain. Actual antidepressant long term treatment has been shown to restore the atrophy of stress-induced nerve cell processes.
현재 우울증 관련 치료는 대체적으로 인지행동치료 (CBT), 대인관계 치료(IPT), 및 상담 치료와 같은 심리적 치료와 전기 자극을 이용한 전기 경련 치료, 항우울제 및 신경안정제 등을 이용한 약물치료 등으로 진행되고 있는 상황이며, 또한 주로 사용되고 있는 우울증 치료제는 주로 뇌세포 간의 정보 전달을 담당하는 ‘세로토닌’이나 ‘노르아드레날린’등의 작용을 활발하게 하여 증상을 개선시키는 것을 목적으로 한다. Currently, depression-related treatments are mainly psychotherapy such as cognitive-behavioral therapy (CBT), interpersonal therapy (IPT), and counseling, electroconvulsive therapy using electrical stimulation, drug therapy using antidepressants and nystagmus The main purpose of the treatment for depression is to improve the symptoms by activating the actions of 'serotonin' or 'noradrenaline', which are mainly responsible for information transmission between brain cells.
이러한 제재들은 각각의 목적에 맞게 개발되어 판매되고 있는데, 세로토닌 또는 노르아드레날린 재흡수 억제 목적으로 하는 SSRI(선택적 세로토닌 재흡수 억제약)인 ‘파록세틴’,‘셀트라린’ 과 SNRI(세로토닌·노르아드레날린 재흡수 억제약)인 ‘밀라세프린’ 및 그 전세대 제약인 3환세대, 4환세대 제약인 ‘아미트립틸린’, ‘아목사핀’등 여러 제제가 있다. These agents are developed and marketed for each purpose. They include SSRIs (selective serotonin reuptake inhibitors), paroxetine, celtralin, and SNRI (serotonin and noradrenaline), which are used to inhibit serotonin or noradrenaline reabsorption Milaseprin, which is an absorption-suppressing drug, and three generations of generic drugs, aminotropicrin, and amosafin, which are four-generation generic drugs.
그러나 이러한 제제들은 치료 효과는 우수하나 질환 특성상 의사 처방이 필요하고 장기적 복용을 필요로 하며, 장기 복용에 따른 구토, 소화기 문제, 전립선 비대증 및 월경 불순에 따른 여성 질환 유발 등의 부작용 등이 존재한다.However, these preparations have excellent therapeutic effect, but due to the nature of the disease, they require a prescription and require long-term use, and there are side effects such as vomiting due to long-term use, digestive problems, enlargement of the prostate gland and induction of female diseases due to menstrual irregularities.
따라서 부작용이 적은 천연물을 유효 성분으로 하는 예방 또는 치료용 제재 및 예방 또는 개선용 식품의 필요성이 대두되고 있다. Therefore, there is a growing need for a preventive or therapeutic agent and a preventive or remedy food containing an effective amount of a natural substance having a low side effect.
한편, 인삼씨 (ginseng seed)는 주로 인삼 재배 및 육종과 관련하여 사용되므로 이를 소재로 하여 성분의 분석 및 연구된 결과 및 상품화가 미비한 상황이다. 인삼(Panax ginseng C.A. Meyer)은, 오가피과 인삼 속에 속하는 식물로 한국, 중국, 일본 등지에서 2,000여년 전부터 사용되어 온 생약으로, 경험적으로 질병을 예방하고 수명 연장을 목적으로 하여 사용되어져 왔으며 중추 신경계 질환 완화, 항암, 면역기능 증진, 항 당뇨, 간기능 항진 등에 효능이 있는 것으로 알려져 있다. 그러나, 인삼씨는 인삼을 재배하기 위한 수단으로만 사용되었기 때문에, 인삼씨 특히 인삼씨에 함유된 오일에 대한 연구는 인삼씨 오일의 지방산 조성과 피토스테롤 함량 분석(비특허문헌 1) 정도이며 조단백 또는 폴리페놀 성분의 함량 정도만 연구되어 있는 실정이다. On the other hand, ginseng seeds are mainly used in relation to ginseng cultivation and breeding, so the analysis and research results of the ingredients and the commercialization thereof are insufficient. Ginseng (Panax ginseng CA Meyer) is a herb that has been used in Korea, China and Japan for over 2,000 years. It has been used for the purpose of preventing diseases and extending life span, , Anti-cancer, immune function enhancement, anti-diabetic, liver function is known to be effective. However, since the ginseng seed was used only as a means for cultivating ginseng, studies on the oil contained in ginseng seeds, especially ginseng seed, were conducted by analyzing the fatty acid composition and phytosterol content of ginseng seed oil (Non-Patent Document 1) Only the content of polyphenol component is studied.
본 발명은 뇌신경세포 보호 및 우울증의 예방, 개선 및 치료를 위해 사용되어 온 기존의 약물들을 대체할 수 있는 천연물 유래의 성분을 발굴하는 것을 목적으로 한다.
The present invention aims at finding components derived from natural materials which can replace conventional drugs that have been used for the prevention, improvement and treatment of neuronal cell protection and depression.
본 발명자들은 스트레스성 질환 중 대표적 질환인 우울증에 대하여 천연물을 대상으로 연구를 진행하던 중 산업적으로 그 가치성이 낮은 인삼씨의 추출물이 뇌신경세포 보호 활성을 나타내며 우울증을 예방, 개선 또는 치료하는 효과를 갖고 있음을 확인하고 본 발명을 완성하였다.The inventors of the present invention have conducted research on natural products for depression, a representative disease of stress diseases, and have found that the extract of ginseng seed having low industrial value exhibits neuronal cell protective activity and has an effect of preventing, improving or treating depression And completed the present invention.
본 발명은 인삼씨 추출물의 뇌신경세포 보호 및 우울증의 예방, 개선 및 치료를 위한 신규 용도, 인삼씨 추출물을 유효성분으로 포함하는 뇌신경세포 보호 및 우울증의 예방, 개선 및 치료용 약제학적 조성물, 치료상 유효량의 인삼씨 추출물을 대상체에 투여하는 것을 포함하는 뇌신경세포 보호 및 우울증의 예방, 개선 및 치료방법을 제공한다. The present invention relates to a novel use of ginseng seed extract for the prevention and improvement and treatment of neuronal cell protection and depression, a pharmaceutical composition for prevention, improvement and treatment of neuronal cell protection and depression comprising ginseng seed extract as an active ingredient, Comprising administering to a subject an effective amount of a ginseng seed extract. Prevention, improvement, and treatment.
하기 실시예에서는, 인삼씨 추출물을 신경세포인 PC12 cell에 처리하여 코르티코스테론에 대한 신경세포 손상 억제 효과를 확인하였으며 아울러 코르티코스테론에 의한 신경세포 독성에 기인하여 억제되었던 신경세포의 분화 및 재생에 관련된 신경 영양 인자인 BDNF(brain-derived neurotrophic factor)와 신호 전달관련 인자인 CREB(cyclic adenosine monophosphate response element binding protein)의 발현이 증진됨을 확인하였다. 따라서, 인삼씨 추출물은 뇌신경세포 보호 및 우울증의 예방, 개선 및 치료용 조성물의 유효성분으로서 사용될 수 있다. In the following examples, ginseng seed extract was treated with PC12 cell, which is a neuron, to inhibit neuronal cell damage to corticosterone. In addition, neuronal cell differentiation and regeneration inhibited by corticosterone- Induced neurotrophic factor (BDNF) and cyclic adenosine monophosphate response element binding protein (CREB). Therefore, the ginseng seed extract can be used as an active ingredient of a composition for prevention, improvement and treatment of neuronal cell protection and depression.
본 발명에 있어서 우울증은 만성 스트레스에 의해 유발되는 우울장애 (depressive disorder)를 뜻하며 이는 의욕 저하와 우울감을 주요 증상으로 하며 다양한 인지 장애 및 정신 신체적 증상을 일으켜 일상생활의 기능 저하를 가져 오는 질환을 말한다.In the present invention, depression refers to a depressive disorder caused by chronic stress, which is a major symptom of desensitization and depression, and causes a variety of cognitive and psychosomatic symptoms, resulting in impaired function of daily life .
본 발명에 있어서, 인삼씨 추출물은 압착법 또는 용매추출법에 의해 얻어진 추출물을 모두 포함한다. In the present invention, the ginseng seed extract includes all the extracts obtained by the pressing method or the solvent extraction method.
본 발명의 한 구체예에서, 상기 인삼씨 추출물은 물, 유기용매 또는 이들의 혼합물을 추출 용매로서 이용하여 인삼씨로부터 추출된 것일 수 있다. 이 때 사용되는 유기용매의 종류나 물과 유기용매의 혼합 비율은 특별히 제한되지 않는다. In one embodiment of the present invention, the ginseng seed extract may be extracted from ginseng seed using water, an organic solvent, or a mixture thereof as an extraction solvent. The kind of the organic solvent used at this time and the mixing ratio of water and the organic solvent are not particularly limited.
예를 들어, 상기 유기용매는 저급 알코올, 헥산, 아세톤, 에틸 아세테이트, 클로로포름, 및 디에틸에테르로 이루어진 군으로부터 선택된 하나 이상의 용매일 수 있다. 상기 저급 알코올은 탄소수 1 내지 6의 알코올일 수 있다. 예를 들어, 저급 알코올로는 메탄올, 에탄올, 프로판올, 부탄올, 노말-프로판올, 이소-프로판올, 노말-부탄올, 1-펜탄올, 2-부톡시에탄올 또는 에틸렌글리콜 등을 이용할 수 있다. 유기용매는 이 외에도 아세트산, DMFO(dimethyl-formamide), DMSO(dimethyl sulfoxide) 등의 극성 용매, 아세토나이트릴, 에틸 아세테이트, 메틸 아세테이트, 플루오로알칸, 펜탄, 2,2,4-트리메틸펜탄, 데칸, 사이클로헥산, 사이클로펜탄, 디이소부틸렌, 1-펜텐, 1-클로로부탄, 1-클로로펜탄, o-자일렌, 디이소프로필 에테르, 2-클로로프로판, 톨루엔, 1-클로로프로판, 클로로벤젠, 벤젠, 디에틸 에테르, 디에틸 설파이드, 클로로포름, 디클로로메탄, 1,2-디클로로에탄, 어닐린, 디에틸아민, 에테르, 사염화탄소 및 THF(Tetrahydrofuran) 등의 비극성 용매를 사용할 수도 있다.For example, the organic solvent may be one or more solvents selected from the group consisting of lower alcohols, hexane, acetone, ethyl acetate, chloroform, and diethyl ether. The lower alcohol may be an alcohol having 1 to 6 carbon atoms. For example, as the lower alcohol, methanol, ethanol, propanol, butanol, n-propanol, iso-propanol, n-butanol, 1-pentanol, 2-butoxyethanol or ethylene glycol can be used. The organic solvent may be a polar solvent such as acetic acid, dimethyl-formamide (DMFO) or dimethyl sulfoxide (DMSO), acetonitrile, ethyl acetate, methyl acetate, fluoroalkane, pentane, 2,2,4-trimethylpentane, decane 1-pentene, 1-chlorobutane, 1-chloropentane, o-xylene, diisopropyl ether, 2-chloropropane, toluene, 1- chloropropane, chlorobenzene , Non-polar solvents such as benzene, diethyl ether, diethyl sulfide, chloroform, dichloromethane, 1,2-dichloroethane, aniline, diethylamine, ether, carbon tetrachloride and THF (tetrahydrofuran) may be used.
한 구체예에서, 상기 인삼씨 추출물은 인삼씨의 열수 추출물 또는 저급 알코올 추출물일 수 있다. 바람직하게는 인삼씨의 에탄올 추출물일 수 있다. 다른 구체예에서, 상기 인삼씨 추출물은 인삼씨의 헥산 추출물일 수 있다. 본 명세서에서, 유기 용매의 추출물은 유기용매 단독 또는 유기용매와 물의 혼합 용매를 추출용매로 이용하여 추출한 것을 모두 포함한다. 예를 들어, 하수오의 에탄올 추출물은 에탄올 단독을 추출 용매로 사용한 추출물뿐만 아니라, 물과 에탄올의 혼합 용매를 이용하여 추출한 추출물도 포함한다.In one embodiment, the ginseng seed extract may be a hot-water extract or a lower alcohol extract of ginseng seed. Preferably, it may be an ethanol extract of ginseng seeds. In another embodiment, the ginseng seed extract may be a hexane extract of ginseng seed. In the present specification, the extract of organic solvent includes organic solvent alone or extract obtained by using a mixed solvent of organic solvent and water as extraction solvent. For example, the ethanol extract of Sasao includes not only extracts using ethanol alone but also extracts obtained by using a mixed solvent of water and ethanol.
예를 들어, 본 발명의 인삼씨 추출물은 건조된 인삼씨에 중량의 10배 내지 20배, 바람직하게는 15배(w/v)의 물, 에탄올, 메탄올, 부탄올 등의 저급알콜 또는 이들의 혼합용매, 바람직하게는 물 또는 5 내지 95% 에탄올에 가열추출법, 초음파 추출법, 환류 추출법 등의 통상적인 추출방법, 바람직하게는 가열추출법으로 70 내지 120℃, 바람직하게는 80 내지 110℃에서 1 내지 6시간, 바람직하게는 3 내지 5시간 동안 추출하는 제 1단계; 상기 단계에서 수득한 추출물을 여과하여 감압 농축하는 제 2단계; 이를 -50℃내지 -30℃에서, 바람직하게는 -45℃ 내지 -25℃에서, 24 내지 72시간, 바람직하게는 40 내지 55시간동안 동결 건조하는 제 3단계의 제조방법을 통하여 본 발명의 인삼씨 추출물을 수득할 수 있다.For example, the ginseng seed extract of the present invention may be added to dried ginseng seeds in an amount of 10 to 20 times, preferably 15 times (w / v) of water, a lower alcohol such as ethanol, methanol or butanol, Preferably 70 to 120 ° C, preferably 80 to 110 ° C, in a solvent, preferably water or 5 to 95% ethanol by a conventional extraction method such as a heat extraction method, an ultrasonic extraction method or a reflux extraction method, For a period of time, preferably 3 to 5 hours; A second step of filtrating and concentrating the extract obtained in the above step under reduced pressure; And then lyophilized at -50 캜 to -30 캜, preferably at -45 캜 to -25 캜 for 24 to 72 hours, preferably for 40 to 55 hours. Seed extract can be obtained.
본 명세서에서 사용되는 용어 ‘추출물’은 추출물을 추가적으로 분획(fractionation)한 분획물도 포함한다. 즉, 인삼씨 추출물은 상술한 추출용매를 이용하여 얻은 것뿐만 아니라, 여기에 정제과정을 추가적으로 적용하여 얻은 것도 포함한다. 또한, 상기 추출물이나 분획물을 일정한 분자량 컷-오프 값을 갖는 한외 여과막을 통과시켜 얻은 분획, 다양한 크로마토그래피 (크기, 전하, 소수성 또는 친화성에 따른 분리를 위해 제작된 것)에 의한 분리 등, 추가적으로 실시된 다양한 정제 방법을 통해 얻어진 분획도 본 발명의 인삼씨 추출물에 포함된다. As used herein, the term " extract " also includes fractions obtained by further fractionating the extract. That is, the ginseng seed extract is obtained not only by using the above-mentioned extraction solvent but also by additionally applying a purification process thereto. Further, fractions obtained by passing the above extract or fractions through an ultrafiltration membrane having a constant molecular weight cut-off value, separation by various chromatography (manufactured for separation according to size, charge, hydrophobicity or affinity), and the like The fractions obtained through various purification methods were also included in the ginseng seed extract of the present invention.
한 구체예에서, 상기 인삼씨 추출물은 인삼씨의 유기용매 추출물을 제2의 유기용매로 재분획한 분획물일 수 있다. 다른 구체예에서, 상기 인삼씨 추출물은 인삼씨의 저급 알코올 추출물을 제2의 유기용매로 재분획한 분획물일 수 있다. 예를 들어, 상기 인삼씨 추출물은 인삼씨의 에탄올 추출물을 헥산으로 재분획한 분획물일 수 있다.In one embodiment, the ginseng seed extract may be a fraction obtained by fractionating an organic solvent extract of ginseng seed with a second organic solvent. In another embodiment, the ginseng seed extract may be a fraction obtained by re-fractionating a lower alcohol extract of ginseng seed with a second organic solvent. For example, the ginseng seed extract may be a fraction obtained by fractionating an ethanol extract of ginseng seeds with hexane.
본 명세서에서 사용되는 용어 ‘인삼씨 추출물’은 인삼씨에 추출용매를 처리하여 얻은 조추출물뿐만 아니라 인삼씨 추출물의 가공물도 포함한다. 예를 들어, 인삼씨 추출물은 감압 증류 및 동결 건조 또는 분무 건조 등과 같은 추가적인 과정에 의해 분말 상태로 제조될 수 있다.As used herein, the term " ginseng seed extract " includes ginseng seed extract as well as crude extract obtained by treating an extract solvent with ginseng seed. For example, ginseng seed extract may be prepared in powder form by further processes such as vacuum distillation and lyophilization or spray drying.
본 발명의 조성물은, 조성물 총 중량에 대하여 상기 인삼씨 추출물을 0.01 내지 50% 중량으로 포함할 수 있다. 이러한 조성은 이에 한정되는 것은 아니며, 인삼씨 추출물의 농도, 본 발명의 조성물이 투여되는 대상체의 상태, 질환의 종류 및 진행 정도 등에 따라 변할 수 있다. The composition of the present invention may contain the ginseng seed extract in an amount of 0.01 to 50% by weight based on the total weight of the composition. Such a composition is not limited thereto, and may vary depending on the concentration of the ginseng seed extract, the condition of the subject to which the composition of the present invention is administered, the type of disease, and the degree of progression.
한편, 본 명세서에서 용어 ‘유효성분으로 포함하는’이란 인삼씨 추출물의 효능 또는 활성을 달성하는 데 충분한 양을 포함하는 것을 의미한다. 본 발명의 한 구체예에서, 본 발명의 조성물 내에서 인삼씨 추출물은 예를 들어, 0.01 mg/ml 이상, 바람직하게는 0.05 mg/ml 이상, 보다 바람직하게는 0.1 mg/ml 이상, 보다 더 바람직하게는 1 mg/ml 이상 포함된다. 인삼씨 추출물은 천연물로서 과량 투여하여도 인체에 부작용이 없으므로 본 발명의 조성물 내에 포함되는 인삼씨 추출물의 양적 상한은 당업자가 적절한 범위 내에서 선택하여 실시할 수 있다.As used herein, the term " comprising as an active ingredient " means an amount sufficient to achieve the efficacy or activity of ginseng seed extract. In one embodiment of the invention, the ginseng seed extract in the composition of the present invention is administered in an amount of, for example, 0.01 mg / ml or more, preferably 0.05 mg / ml or more, more preferably 0.1 mg / ml or more And more than 1 mg / ml. Since the ginseng seed extract has no adverse effect on the human body even when administered in an excessive amount as a natural product, the quantitative upper limit of the ginseng seed extract contained in the composition of the present invention can be selected by a person skilled in the art within a suitable range.
본 발명에 따른 조성물은 약제학적 조성물 또는 식품 조성물로 활용될 수 있다.The composition according to the present invention can be utilized as a pharmaceutical composition or a food composition.
본 발명의 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.The pharmaceutical composition of the present invention can be prepared by using pharmaceutically acceptable and physiologically acceptable adjuvants in addition to the above-mentioned active ingredients. Examples of the adjuvants include excipients, disintegrants, sweeteners, binders, coating agents, swelling agents, lubricants, A lubricant or a flavoring agent 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 formulated into a pharmaceutical composition containing at least one pharmaceutically acceptable carrier in addition to the above-described active ingredients 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 감미제, 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. The pharmaceutical composition may be in the form of granules, powders, tablets, coated tablets, capsules, suppositories, liquids, syrups, juices, suspensions, emulsions, drops or injectable solutions. For example, for formulation into tablets or capsules, the active ingredient may be combined with an oral, non-toxic pharmaceutically acceptable inert carrier such as ethanol, glycerol, water, and the like. Also, if desired or necessary, suitable binders, lubricants, disintegrants and coloring agents may also be included as a 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, tracker candles 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.
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. Acceptable pharmaceutical carriers for compositions that are formulated into a liquid solution include sterile water and sterile water suitable for the living body such as saline, sterile water, Ringer's solution, buffered saline, albumin injection solution, dextrose solution, maltodextrin solution, glycerol, One or more of these components may be mixed and used. If necessary, other conventional additives such as an antioxidant, a buffer, and a bacteriostatic agent may be added. 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.
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. Further, it can be suitably formulated according to each disease or ingredient, using the method disclosed in Remington's Pharmaceutical Science, Mack Publishing Company, Easton PA as an appropriate method in the field.
본 발명의 약제학적 조성물은 경구 또는 비경구로 투여할 수 있고, 비경구 투여인 경우에는 정맥내 주입, 피하 주입, 근육 주입, 복강 주입, 경피 투여 등으로 투여할 수 있으며, 바람직하게는 경구 투여이다.The pharmaceutical composition of the present invention can be administered orally or parenterally. In the case of parenteral administration, the composition can be administered by intravenous injection, subcutaneous injection, muscle injection, intraperitoneal injection, transdermal administration, etc., .
본 발명의 약제학적 조성물의 적합한 투여량은 제제화 방법, 투여 방식, 환자의 연령, 체중, 성, 병적 상태, 음식, 투여 시간, 투여 경로, 배설 속도 및 반응 감응성과 같은 요인들에 의해 다양하며, 보통으로 숙련된 의사는 소망하는 치료 또는 예방에 효과적인 투여량을 용이하게 결정 및 처방할 수 있다. 본 발명의 바람직한 구현예에 따르면, 본 발명의 약제학적 조성물의 1일 투여량은 0.0001-10g/㎏이다.The appropriate dosage of the pharmaceutical composition of the present invention varies depending on factors such as the formulation method, administration method, age, body weight, sex, pathological condition, food, administration time, administration route, excretion rate and responsiveness of the patient, Usually, a skilled physician can readily determine and prescribe dosages effective for the desired treatment or prophylaxis. According to a preferred embodiment of the present invention, the daily dosage of the pharmaceutical composition of the present invention is 0.0001-10 g / kg.
본 발명의 약제학적 조성물은 당해 발명이 속하는 기술분야에서 통상의 지식을 가진 자가 용이하게 실시할 수 있는 방법에 따라, 약제학적으로 허용되는 담체 및/또는 부형제를 이용하여 제제화 함으로써 단위 용량 형태로 제조되거나 또는 다용량 용기 내에 내입시켜 제조될 수 있다. 이때 제형은 오일 또는 수성 매질중의 용액, 현탁액 또는 유화액 형태이거나 엑스제, 분말제, 과립제, 정제 또는 캅셀제 형태일 수도 있으며, 분산제 또는 안정화제를 추가적으로 포함할 수 있다.The pharmaceutical composition of the present invention may be formulated into a unit dose form by formulating it using a pharmaceutically acceptable carrier and / or excipient according to a method which can be easily carried out by a person having ordinary skill in the art to which the present invention belongs. Or by intrusion into a multi-dose container. The formulations may be in the form of solutions, suspensions or emulsions in oils or aqueous media, or in the form of excipients, powders, granules, tablets or capsules, and may additionally contain dispersing or stabilizing agents.
본 발명은 또한 인삼씨 추출물을 유효성분으로 포함하는 뇌신경세포 보호 및 우울증의 예방 및 개선용 식품 조성물을 제공한다.The present invention also provides a food composition for prevention and improvement of neuronal cell protection and depression comprising ginseng seed extract as an active ingredient.
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, 알코올 음료류, 과자류, 다이어트바, 유제품, 육류, 초코렛, 피자, 라면, 기타 면류, 껌류, 아이스크림류, 비타민 복합제, 건강보조식품류 등이 있다.The food composition according to the present invention can be formulated in the same manner as the above pharmaceutical composition and 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, alcoholic beverages, confectioneries, diet bars, dairy products, meat, chocolates, pizza, ram noodles, other noodles, gums, ice cream, .
본 발명의 식품 조성물은 유효성분으로서 인삼씨 추출물뿐만 아니라, 식품 제조 시에 통상적으로 첨가되는 성분을 포함할 수 있으며, 예를 들어, 단백질, 탄수화물, 지방, 영양소, 조미제 및 향미제를 포함한다. 상술한 탄수화물의 예는 모노사카라이드, 예를 들어, 포도당, 과당 등; 디사카라이드, 예를 들어 말토스, 슈크로스, 올리고당 등; 및 폴리사카라이드, 예를 들어 덱스트린, 사이클로덱스트린 등과 같은 통상적인 당 및 자일리톨, 소르비톨, 에리트리톨 등의 당알콜이다. 향미제로서 천연 향미제 [타우마틴, 스테비아 추출물 (예를 들어 레바우디오시드 A, 글리시르히진 등]) 및 합성 향미제(사카린, 아스파르탐 등)를 사용할 수 있다. 예컨대, 본 발명의 식품 조성물이 드링크제와 음료류로 제조되는 경우에는 본 발명의 인삼씨 추출물 이외에 구연산, 액상과당, 설탕, 포도당, 초산, 사과산, 과즙, 및 각종 식물 추출액 등을 추가로 포함시킬 수 있다.The food composition of the present invention may contain not only ginseng seed extract as an active ingredient, but also components that are ordinarily added in the manufacture of food, including, for example, proteins, carbohydrates, fats, nutrients, seasonings and flavors . Examples of the above-mentioned carbohydrates are monosaccharides such as glucose, fructose, and the like; Disaccharides such as maltose, sucrose, oligosaccharides and the like; And polysaccharides such as dextrin, cyclodextrin and the like, and sugar alcohols such as xylitol, sorbitol and erythritol. Natural flavorings such as tau martin and stevia extract (e.g., rebaudioside A and glycyrrhizin) and synthetic flavorings (saccharine, aspartame, etc.) can be used as flavorings. For example, when the food composition of the present invention is prepared from a drink and a beverage, citric acid, liquid fructose, sugar, glucose, acetic acid, malic acid, juice, various plant extracts and the like may be further added in addition to the ginseng seed extract of the present invention .
본 발명은 상기 인삼씨 추출물을 유효성분으로 포함하는 뇌신경세포 보호 및 우울증의 예방 및 개선용 식품 조성물을 포함하는 건강기능식품을 제공한다. 건강기능식품이란, 인삼씨 추출물을 음료, 차류, 향신료, 껌, 과자류 등의 식품소재에 첨가하거나, 캡슐화, 분말화, 현탁액 등으로 제조한 식품으로, 이를 섭취할 경우 건강상 특정한 효과를 가져오는 것을 의미하나, 일반 약품과는 달리 식품을 원료로 하여 약품의 장기 복용시 발생할 수 있는 부작용 등이 없는 장점이 있다. 이와 같이 하여 얻어지는 본 발명의 건강기능식품은, 일상적으로 섭취하는 것이 가능하기 때문에 매우 유용하다. 이와 같은 건강기능식품에 있어서의 인삼씨 추출물의 첨가량은, 대상인 건강기능식품의 종류에 따라 달라 일률적으로 규정할 수 없지만, 식품 본래의 맛을 손상시키지 않는 범위에서 첨가하면 되며, 대상 식품에 대하여 통상 0.01 내지 50 중량%, 바람직하기로는 0.1 내지 20 중량%의 범위이다. 또한, 환제, 과립제, 정제 또는 캡슐제 형태의 건강기능식품의 경우에는 통상 0.1 내지 100 중량% 바람직하기로는 0.5 내지 80 중량%의 범위에서 첨가하면 된다. 한 구체예에서, 본 발명의 건강기능식품은 환제, 정제, 캡슐제 또는 음료의 형태일 수 있다.The present invention provides a health functional food comprising the ginseng seed extract as an active ingredient and a food composition for preventing and ameliorating neuronal cell protection and depression. Health functional foods are foods made by adding ginseng seed extract to food materials such as beverages, tea, spices, gum and confectionary, or encapsulated, powdered, or suspended, However, unlike general medicine, there is an advantage that there is no side effect that can occur when a food is used as a raw material and a drug is taken for a long time. The health functional food of the present invention thus obtained is very useful because it can be ingested routinely. The amount of the ginseng seed extract added to such a health functional food can not be uniformly determined depending on the type of the health functional food to which it is added but may be added within a range that does not impair the original taste of the food, 0.01 to 50% by weight, preferably 0.1 to 20% by weight. In the case of health functional foods in the form of pills, granules, tablets or capsules, they may be added usually in the range of 0.1 to 100% by weight, preferably 0.5 to 80% by weight. In one embodiment, the health functional food of the present invention may be in the form of a pill, tablet, capsule or beverage.
본 발명은 또한 뇌신경세포 보호 및 우울증의 예방, 개선 및 치료용 의약 또는 식품의 제조를 위한 상기 인삼씨 추출물의 용도를 제공한다. 상기한 바와 같이 인삼씨 추출물은 뇌신경세포 보호 및 우울증의 예방, 개선 및 치료를 위한 용도로 이용될 수 있다.The present invention also provides the use of said ginseng seed extract for the manufacture of a medicament or food for the prevention, amelioration and treatment of neuronal cell protection and depression. As described above, the ginseng seed extract can be used for prevention, improvement and treatment of brain nerve cell protection and depression.
또한 본 발명은 포유동물에게 유효량의 인삼씨 추출물을 투여하는 것을 포함하는 뇌신경세포 보호 및 우울증의 예방, 개선 및 치료 방법을 제공한다.The present invention also provides a method for preventing, ameliorating and treating neuronal cell protection and depression, which comprises administering an effective amount of ginseng seed extract to a mammal.
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 a human.
여기에서 사용된 용어 '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 해당 질환 또는 장애의 증상의 완화를 유도하는 양을 포함한다. 본 발명의 유효 성분에 대한 유효량 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 예방, 치료 또는 개선 방법에 있어서, 성인의 경우, 인삼씨 추출물을 1일 1회 내지 수회 투여시, 0.001 ㎎/kg 내지 10g/kg의 용량으로 투여하는 것이 바람직하다.The term " effective amount " as used herein refers to the amount of 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, physician or other clinician, ≪ / RTI > inducing a reduction of the symptoms of the disease or disorder. It will be apparent to those skilled in the art that the effective amount and the administration frequency of the active ingredient of the present invention will vary depending on the desired effect. Thus, the optimal dosage to be administered can be readily determined by those skilled in the art and will vary with the nature of the disease, the severity of the disease, the amount of active and other ingredients contained in the composition, the type of formulation, and the age, The age, body weight, sex, diet, time of administration, route of administration and fraction of the composition, duration of treatment, concurrent medication, and the like. In the prevention, treatment, or improvement of the present invention, it is preferable that the ginseng seed extract is administered at a dose of 0.001 mg / kg to 10 g / kg once or several times a day.
본 발명의 치료방법에서 인삼씨 추출물을 유효 성분으로 포함하는 조성물은 경구, 직장, 정맥내, 동맥내, 복강내, 근육내, 흉골내, 경피, 국소, 안구내 또는 피내 경로를 통해 통상적인 방식으로 투여할 수 있다.
The composition comprising the ginseng seed extract as an active ingredient in the treatment method of the present invention can be administered orally or rectally through the oral, rectal, intravenous, intraarterial, intraperitoneal, intramuscular, intrasternal, transdermal, topical, ≪ / RTI >
본 발명의 인삼씨 추출물을 유효성분으로 포함하는 조성물은 우울증 유발과 관련있는 코르티졸에 의한 독성에 대한 신경 세포 보호 효과 및 신경 영양 인자의 발현 개선 효과를 나타내므로 우울증 발생 및 진행을 예방 또는 개선하거나, 우울증을 치료하는데 효과적으로 사용될 수 있다.
The composition comprising the ginseng seed extract of the present invention as an active ingredient exhibits a neuroprotective effect on the toxicity caused by cortisol and a neurotrophic factor expression improving effect related to the induction of depression so that the occurrence and progress of depression can be prevented or improved, Can be effectively used to treat depression.
도 1은 인삼씨의 물 및 에탄올 추출물의 세포 독성에 대한 효과를 보여준다(Control: 무처리 대조군, 0: 인삼씨 열수 추출물, 50: 50% EtOH 인삼씨 추출물, 80: 80% EtOH 인삼씨 추출물, 시료의 최종농도: 0.1 mg/ml 및 0.5 mg/ml).
도 2은 인삼씨의 물 및 에탄올 추출물의 코르티코스테론으로부터의 신경세포 보호 활성을 보여준다(Control: 무처리 대조군, control-1: 코르티코스테론 처리 (0.2 mM, 48hr), 0: 인삼씨 열수 추출물, 50: 50% EtOH 인삼씨 추출물, 80: 80% EtOH 인삼씨 추출물).
도 3은 인삼씨의 물 및 에탄올 추출물이 코르티코스테론에 의해 야기된 신경세포 영양 인자의 발현 억제를 개선함을 보여준다 (Control: 무처리 대조군, control-1: 코르티코스테론 처리 (0.2 mM, 48hr), 0: 인삼씨 열수 추출물, 50: 50% EtOH 인삼씨 추출물, 80; 80% EtOH 인삼씨 추출물).Figure 1 shows the effect of water and ethanol extracts of ginseng seeds on cytotoxicity (Control: untreated control group, 0: ginseng seed hydrothermal extract, 50: 50% EtOH ginseng seed extract, 80: 80% EtOH ginseng seed extract, Final concentrations of sample: 0.1 mg / ml and 0.5 mg / ml).
Figure 2 shows the protective activity of water and ethanol extract of ginseng seeds from corticosterone (Control: untreated control, control-1: corticosterone treatment (0.2 mM, 48 hr), 0: , 50: 50% EtOH ginseng seed extract, 80: 80% EtOH ginseng seed extract).
Figure 3 shows that the water and ethanol extracts of ginseng seed improve the inhibition of the expression of nerve cell nutrients caused by corticosterone (Control: untreated control, control-1: corticosterone treatment (0.2 mM, 48 hrs ), 0: ginseng hot water extract, 50: 50% EtOH ginseng seed extract, 80: 80% EtOH ginseng seed extract).
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 of achieving them will become apparent with reference to the embodiments described in detail below. The present invention may, however, be embodied in many different forms and should not be construed as being limited to the embodiments set forth herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete, and will fully convey the scope of the invention to those skilled in the art. Is provided to fully convey the scope of the invention to those skilled in the art, and the invention is only defined by the scope of the claims.
실시예Example 1. 인삼씨의 1. Ginseng seed 열수Heat number 추출물의 제조 Preparation of extract
건조시킨 인삼씨 시료를 마쇄하여 마쇄한 시료 3.2 kg에 정제수 36 L를 가하여 100℃에서 4시간 동안 가열추출하고 여액을 감압 농축하여 동결건조기를 이용하여 -40℃에서 48시간 동안 동결 건조시켜 본 발명의 인삼씨 열수 추출물을 수득하여 하기 실험예의 시료로 사용하였다.
The dried ginseng seed sample was ground to obtain 3.2 kg of the ground sample. 36 L of purified water was added and heated at 100 ° C. for 4 hours. The filtrate was concentrated under reduced pressure and freeze-dried at -40 ° C. for 48 hours using a freeze dryer, Ginseng seed hot water extract was used as a sample of the following experimental example.
실시예Example 2. 인삼씨의 에탄올 추출물의 제조 2. Preparation of Ethanol Extract of Ginseng Seed
2-1. 인삼씨의 50% 에탄올 추출물의 제조2-1. Production of 50% Ethanol Extract of Ginseng Seed
건조시킨 인삼씨 시료를 마쇄하여 마쇄한 시료(3.2 kg)에 50% 에탄올 36 L를 가하여 84℃에서 4시간 동안 가열추출하고 여액을 감압 농축하여 동결건조기를 이용하여 -40℃에서 48시간 동안 동결건조시켜 본 발명의 인삼씨 50% 에탄올 추출물을 수득하여 하기 실험예의 시료로 사용하였다.
The dried ginseng seed sample was crushed, and 36 L of 50% ethanol was added to the ground sample (3.2 kg), and the mixture was heated at 84 ° C. for 4 hours. The filtrate was concentrated under reduced pressure and freeze-dried at -40 ° C. for 48 hours Dried to obtain a 50% ethanol extract of ginseng seed of the present invention and used as a sample of the following experimental example.
2-2. 인삼씨의 80 % 에탄올 추출물의 제조2-2. Production of 80% Ethanol Extract of Ginseng Seed
건조시킨 인삼씨 시료를 마쇄하여 마쇄한 시료 (3.2 kg)에 95% 에탄올 36 L를 가하여 82℃에서 4시간 동안 가열추출하고 여액을 감압 농축하여 동결건조기를 이용하여 -40℃에서 48시간 동안 동결건조시켜 본 발명의 인삼씨 95% 에탄올 추출물 수득하여 하기 실험예의 시료로 사용하였다.
The dried ginseng seeds were crushed, and 36 L of 95% ethanol was added to the ground sample (3.2 kg), and the mixture was heated at 82 ° C for 4 hours. The filtrate was concentrated under reduced pressure and freeze-dried at -40 ° C for 48 hours Dried to obtain a 95% ethanol extract of ginseng seed of the present invention and used as a sample of the following experimental example.
실험예Experimental Example 1. 세포독성 실험 1. Cytotoxicity experiment
상기 실시예에서 수득한 시료의 세포독성을 실험하고자 MTT assay 법(Yun-Lian Lina, Guei-JaneWang, Chuen-Lin Huan, Yi-Chao Lee, Wei-Chen Liao, Wen-Lin Lai, Yen-Ju Lin, Nai-Kuei Huan,.J. Ethnopharmacology, 122; 417-425 (2009))을 이용하여 하기와 같이 실험을 수행하였다. In order to test the cytotoxicity of the samples obtained in the above examples, MTT assay method (Yun-Lian Lina, Guei-Jane Wang, Chuen-Lin Huan, Yi-Chao Lee, Wei-Chen Liao, Wen- , Nai-Kuei Huan, J. Ethnopharmacology, 122: 417-425 (2009)).
PC12 세포 (rat pheochromocytoma cell, American Type Culture Collection (ATCC; Manassas, VA))을 10% fetal bovin serum (FBS, Gibco-BRL ((Gaithersburg, MD)) 및 1% antimicotics/antibiotics (Gibco-BRL)를 함유한 RPMI-1640 배지(Gibco-BRL)에서 배양하여 세포수가 104-106 세포/ml이 되도록 배양하였다. (Gibco-BRL, Gaithersburg, MD) and 1% antimycotics / antibiotics (Gibco-BRL) supplemented with 10% fetal bovine serum cultured in RPMI-1640 medium containing one (Gibco-BRL) the number of cells were cultured to be 10 4 -10 6 cells / ml.
배양 세포들을 96-웰 플레이트로 옮겨 주어 세포수가 웰당 1x104로 배양한 다음, 상기 실시예에서 수득한 인삼씨 추출물을 5% DMSO에 1 mg/ml 및 5 mg/ml을 녹인 후 15 ㎕씩 넣고 (최종 농도가 0.1 mg/ml 및 0.5 mg/ml)48 시간 37℃에서 반응시킨 후, PBS에 녹인 MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, M2128, Sigma) 시약 2 mg/ml을 각 웰당 15 ㎕씩 넣은 후 37℃에서 90분간 반응 후 570nm/630nm 에서 흡광도 값을 측정한 후, 하기 수학식 1을 이용하여 계산하였다. The cultured cells were transferred to a 96-well plate, and the number of cells was cultured at 1 × 10 4 cells / well. Then, 1 mg / ml and 5 mg / ml of the ginseng seed extract obtained in the above Example were dissolved in 5% DMSO, (Final concentrations of 0.1 mg / ml and 0.5 mg / ml) for 48 hours at 37 ° C and then reacted with MTT (3- (4,5-dimethylthiazol-2-yl) -2,5-diphenyltetrazolium bromide, M2128 , Sigma) Reagent 2 mg / ml was added to each well at 15. After incubation at 37 캜 for 90 minutes, absorbance was measured at 570 nm / 630 nm and calculated using the following equation (1).
[수학식 1][Equation 1]
세포 생존율(%) = (흡광도(시료)/흡광도(대조군))× 100Cell survival rate (%) = (absorbance (sample) / absorbance (control group) ) 100
도 1은 인삼씨의 물 및 에탄올 추출물의 세포 독성에 대한 효과를 보여준다(Control: 무처리군, 0: 인삼씨 열수 추출물, 50: 50% EtOH 인삼씨 추출물, 80: 80% EtOH 인삼씨 추출물, 시료의 최종농도: 200㎍/ml). 도 2에 나타난 바와 같이, 인삼씨 추출물 시료 모두 세포 독성이 없음을 확인할 수 있었다.
Figure 1 shows the effects of water and ethanol extracts of ginseng seeds on cytotoxicity (Control: no treatment, 0: ginseng seed hydrothermal extract, 50: 50% EtOH ginseng seed extract, 80: 80% EtOH ginseng seed extract, Final concentration of sample: 200 占 퐂 / ml). As shown in FIG. 2, it was confirmed that the ginseng seed extract samples were not cytotoxic.
실험예Experimental Example 2. 2. 코르티코스테론에Corticosterone 대한 신경세포 보호 활성의 측정 Measurement of protective activity of neuron
상기 실시예에서 수득한 시료의 코르티코스테론에 의한 독성으로부터 신경세포 보호 활성을 실험하고자 Xiao-Qing Tang 등의 방법(Xiao-Qing Tang, Jian-Qiang Feng, Jin Chen, Pei-Xi Chen, Jun-Li Zhi, Yu Cui, Rui-Xian Guo, Hui-Min Yu; Brain Research, 1057 57-64(2005))을 이용하여 하기와 같이 실험을 수행하였다.To examine the protective activity of nerve cells from the toxicity of corticosterone in the samples obtained in the above examples, Xiao-Qing Tang, Jian-Qiang Feng, Jin Chen, Pei-Xi Chen, Jun- Li Zhi, Yu Cui, Rui-Xian Guo, Hui-Min Yu; Brain Research, 1057 57-64 (2005)).
PC12 세포를 96-웰 플레이트에 antimicotics/antibiotics를 함유한 RPMI-1640 배지에 배양하여 세포수가 웰당 1x104이 되었을 때, 상기 실시예에서 수득한 인삼씨 추출물 시료를 2mg/ml의 농도로 5% DMSO에 녹인 후, 각각 15 ㎕씩 넣고 2-4시간 37℃에서 전처리(pre-incubation)한 후, 0.2 mM 코르티코스테론을 48 시간 처리하여 산화적 스트레스(oxidative stress)를 유도한 후, 상기 실험예 1의 MTT 어세이법을 이용하여 신경세포 보호 활성을 측정하였다. 대조군은 시료를 아무것도 처리하지 않았으며, 음성대조군은 0.2 mM 코르티코스테론을 48시간 처리하여 측정하였다.PC12 cells were cultured in a 96-well plate in RPMI-1640 medium containing antimicotics / antibiotics. When the number of cells became 1 × 10 4 per well, the ginseng seed extract obtained in the above Example was dissolved in 5% DMSO , 15 μl of each of them was added to each well, pre-incubated at 37 ° C for 2-4 hours, treated with 0.2 mM corticosterone for 48 hours to induce oxidative stress, 1 < / RTI > MTT assays. The control group was not treated with anything and the negative control group was treated with 0.2 mM corticosterone for 48 hours.
도 2는 인삼씨의 물 및 에탄올 추출물의 코르티코스테론으로부터 신경세포 보호 활성을 보여준다(Control: 무처리군, con-1: 코르티코스테론 처리 (0.2 mM, 48hr), 0; 인삼씨 열수 추출물, 50; 50%EtOH 인삼씨 추출물, 80; 80% EtOH 인삼씨 추출물). 도 2에 나타난 바와 같이, 코르티코스테론에 의해 유발된 산화적 스트레스로 인하여 세포 활성이 60% 정도로 낮아졌으며, 인삼씨 추출물에서의 높은 보호 활성을 나타냄을 보였다.
2 shows the protective activity of nerve cells from corticosterone of water and ethanol extract of ginseng seeds (Control: untreated group, con-1: corticosterone treatment (0.2 mM, 48 hr) 50; 50% EtOH ginseng seed extract; 80; 80% EtOH ginseng seed extract). As shown in FIG. 2, the cell activity was lowered to about 60% due to the oxidative stress induced by corticosterone and showed a high protective activity in the ginseng seed extract.
실험예Experimental Example 3. 3. 코르티코스테론에Corticosterone 의해 유발되는 신경 독성에 대한 신경세포 성장인자들의 발현 증진 활성 효과 Effect of Neural Cell Growth Factors on Neurotoxicity Induced by Neuronal Cells
상기 실시예에서 수득한 인삼씨 추출물 시료가 코르티코스테론에 의한 뇌신경 독성으로부터 신경세포 성장 영양인자의 발현을 증진시키는지 확인하고자 하기와 같이 실험을 수행하였다.Experiments were carried out in order to confirm whether the ginseng seed extract obtained in the above Examples promotes the expression of nerve cell growth factor from corticosterone-induced neuronal toxicity.
PC12 세포를 6-웰 플레이트에 antimicotics/antibiotics를 함유한 RPMI-1640 배지에 배양하여 세포수가 웰당 2x105이 되었을 때, 상기 실시예에서 수득한 인삼씨 추출물을 2mg/ml의 농도로 5% DMSO에 녹인 후, 각각 15 ㎕씩 넣고 2-4시간 37℃에서 전처리(pre-incubation)한 후, 0.2 mM 코르티코스테론을 48 시간 처리하여 신경세포 독성을 유발하여, qPCR 어세이법을 이용하여 신경세포 성장 영양인자 및 관련인자들의 발현정도를 측정하였다. 대조군(control)은 시료를 아무것도 처리하지 않았으며, 음성대조군(control-1)은 코르티코스테론만을 처리하여 측정하였다. PC12 cells were cultured in 6-well plate in RPMI-1640 medium containing antimicotics / antibiotics. When the number of cells was 2x10 5 per well, the ginseng seed extract obtained in the above Example was dissolved in 5% DMSO After dissolving, 15 μl of each solution was pre-incubated at 37 ° C for 2-4 hours, and 0.2 mM corticosterone was treated for 48 hours to induce neuronal cytotoxicity. Growth nutrients and related factors were measured. Controls did not process any samples, and negative control (control-1) was measured by treatment with corticosterone alone.
본 실험예에서 신경세포 성장 영양인자 및 관련인자로 사용된 BDNF (brain-derived neurotrophic factor)는 주된 신경세포 성장 영양인자로써 신경세포의 생존 및 발현에 주된 영향을 주는 인자이며, CREB(cyclic adenosine monophosphate response element nindint protein)은 세포 신호전달 경로 및 BDNF의 발현에 밀접한 영향을 주는 인자로 알려져 있다. 또한 MAP-4(microtubule-associated protein 4)는 CREB의 발현과 밀접하게 관련있는 non-neuronal micortubule-associated protein으로 알려져 있으며 세포주기(cell cycle)와 연관있는 인자로 알려져 있다. The brain-derived neurotrophic factor (BDNF) used as a neurotrophic factor and related factor in this experiment is a major factor affecting the survival and expression of neuronal cells as a major neurotrophic factor. CRB (cyclic adenosine monophosphate response element nindint protein) is known to be a factor that closely affects cell signaling pathway and BDNF expression. MAP-4 (microtubule-associated protein 4) is known to be a non-neuronal micortubule-associated protein closely related to the expression of CREB and is known to be associated with the cell cycle.
도 3은 인삼씨의 물 및 에탄올 추출물이 코르티코스테론에 의해 억제된 신경세포 영양 인자의 발현을 개선함을 보여준다(Control: 무처리 대조군, control-1: 코르티코스테론 처리 (0.2 mM, 48hr), 0; 인삼씨 열수 추출물, 50; 50%EtOH 인삼씨 추출물, 80; 80% EtOH 인삼씨 추출물). 도 3에 나타난 바와 같이, 코르티코스테론에 의해 유발된 신경세포 독성으로 인하여 신경세포 성장 인자 및 관련 인자의 발현정도가 40-60% 정도로 낮아졌으며, 인삼씨 추출물의 처리 결과 관련 인자들의 발현 억제 정도가 개선되는 것을 확인할 수 있었다. .
FIG. 3 shows that water and ethanol extracts of ginseng seed improve the expression of nerve cell nutrients inhibited by corticosterone (Control: untreated control, control-1: corticosterone treatment (0.2 mM, 48 hr) Ginseng seed extract, 50% EtOH ginseng seed extract, 80; 80% EtOH ginseng seed extract). As shown in FIG. 3, the neuronal cell toxicity induced by corticosterone lowered the expression level of neuronal cell growth factor and related factor to about 40-60%. The inhibitory effect of the ginseng seed extract on the expression of related factors Was improved. .
이하, 본 발명의 추출물을 함유하는 조성물의 제제예를 설명하나, 본 발명은 이를 한정하고자 함이 아닌 단지 구체적으로 설명하고자 함이다.
Hereinafter, formulation examples of the composition containing the extract of the present invention will be described, but the present invention is not intended to be limited thereto but is specifically described.
제제예Formulation example 1. One. 산제의Sanje 제조 Produce
인삼씨 열수 또는 에탄올 추출물 20 mgGinseng seed hydrothermal or
유당 100 mg
탈크 10 mg
Talc 10 mg
상기의 성분들을 혼합하고 기밀포에 충진하여 산제를 제조한다.
The above components are mixed and filled in airtight bags to prepare powders.
제제예Formulation example 2. 정제의 제조 2. Preparation of tablets
인삼씨 열수 또는 에탄올 추출물 10 mgGinseng seed hot water or ethanol extract 10 mg
옥수수전분 100 mg
유당 100 mg
스테아린산 마그네슘 2 mg
Magnesium stearate 2 mg
상기의 성분들을 혼합한 후 통상의 정제의 제조방법에 따라서 타정하여 정제를 제조한다.
After mixing the above components, tablets are prepared by tableting according to the usual preparation method of tablets.
제제예Formulation example 3. 캅셀제의 제조 3. Preparation of capsules
인삼씨 열수 또는 에탄올 추출물 10 mgGinseng seed hot water or ethanol extract 10 mg
결정성 셀룰로오스 3 mgCrystalline cellulose 3 mg
락토오스 14.8 mgLactose 14.8 mg
마그네슘 스테아레이트 0.2 mg
Magnesium stearate 0.2 mg
통상의 캅셀제 제조방법에 따라 상기의 성분을 혼합하고 젤라틴 캡슐에 충전하여 캅셀제를 제조한다.
The above components are mixed in accordance with a conventional method for producing a capsule, and filled in a gelatin capsule to prepare a capsule.
제제예Formulation example 4. 주사제의 제조 4. Preparation of injections
인삼씨 열수 또는 에탄올 추출물 10 mgGinseng seed hot water or ethanol extract 10 mg
만니톨 180 mg180 mg mannitol
주사용 멸균 증류수 2974 mgSterile sterilized water for injection 2974 mg
Na2HPO4 ,12H2O 26 mg
Na 2 HPO 4 , 12H 2 O 26 mg
통상의 주사제의 제조방법에 따라 1 앰플당 (2 ㎖) 상기의 성분 함량으로 제조한다.
(2 ml) per ampoule in accordance with the usual injection method.
제제예Formulation example 5. 5. 액제의Liquid 제조 Produce
인삼씨 열수 또는 에탄올 추출물 20 mgGinseng seed hydrothermal or
이성화당 10 g10 g per isomer
만니톨 5 g5 g mannitol
정제수 적량Purified water quantity
통상의 액제의 제조방법에 따라 정제수에 각각의 성분을 가하여 용해시키고 레몬향을 적량 가한 다음 상기의 성분을 혼합한 다음 정제수를 가하여 전체를 정제수를 가하여 전체 100 ml로 조절한 후 갈색병에 충진하여 멸균시켜 액제를 제조한다.
Each component was added and dissolved in purified water according to the usual liquid preparation method, and the lemon flavor was added in an appropriate amount. Then, the above components were mixed, and purified water was added thereto. The whole was added with purified water to adjust the total volume to 100 ml, And sterilized to prepare a liquid preparation.
제제예Formulation example 6. 건강 식품의 제조 6. Manufacture of health food
인삼씨 열수 또는 에탄올 추출물 1000 mgGinseng seeds Hot water or ethanol extract 1000 mg
비타민 혼합물 적량Vitamin mixture quantity
비타민 A 아세테이트 70 ㎍70 [mu] g of vitamin A acetate
비타민 E 1.0 ㎎Vitamin E 1.0 mg
비타민 B1 0.13 ㎎0.13 mg vitamin B1
비타민 B2 0.15 ㎎0.15 mg of vitamin B2
비타민 B6 0.5 ㎎0.5 mg vitamin B6
비타민 B12 0.2 ㎍0.2 [mu] g vitamin B12
비타민 C 10 ㎎10 mg vitamin C
비오틴 10 ㎍Biotin 10 μg
니코틴산아미드 1.7 ㎎Nicotinic acid amide 1.7 mg
엽산 50 ㎍50 ㎍ of folic acid
판토텐산 칼슘 0.5 ㎎Calcium pantothenate 0.5 mg
무기질 혼합물 적량Mineral mixture quantity
황산제1철 1.75 ㎎1.75 mg of ferrous sulfate
산화아연 0.82 ㎎0.82 mg of zinc oxide
탄산마그네슘 25.3 ㎎Magnesium carbonate 25.3 mg
제1인산칼륨 15 ㎎15 mg of potassium phosphate monobasic
제2인산칼슘 55 ㎎Secondary calcium phosphate 55 mg
구연산칼륨 90 ㎎Potassium citrate 90 mg
탄산칼슘 100 ㎎100 mg of calcium carbonate
염화마그네슘 24.8 ㎎
24.8 mg of magnesium chloride
상기의 비타민 및 미네랄 혼합물의 조성비는 비교적 건강식품에 적합한 성분을 바람직한 실시예로 혼합 조성하였지만, 그 배합비를 임의로 변형 실시하여도 무방하며, 통상의 건강식품 제조방법에 따라 상기의 성분을 혼합한 다음, 과립을 제조하고, 통상의 방법에 따라 건강식품 조성물 제조에 사용할 수 있다.
Although the composition ratio of the above-mentioned vitamin and mineral mixture is comparatively mixed with a composition suitable for health food as a preferred embodiment, the compounding ratio may be arbitrarily modified, and the above ingredients are mixed according to a conventional method for producing healthy foods , Granules can be prepared and used in the manufacture of health food compositions according to conventional methods.
제제예Formulation example 7. 건강 음료의 제조 7. Manufacture of health drinks
인삼씨 열수 또는 에탄올 추출물 1000 mgGinseng seeds Hot water or ethanol extract 1000 mg
구연산 1000 ㎎Citric acid 1000 mg
올리고당 100 g100 g of oligosaccharide
매실농축액 2 gPlum concentrate 2 g
타우린 1 gTaurine 1 g
정제수를 가하여 전체 900 ㎖
Purified water was added to a total of 900 ml
통상의 건강음료 제조방법에 따라 상기의 성분을 혼합한 다음, 약 1시간동안 85℃에서 교반 가열한 후, 만들어진 용액을 여과하여 멸균된 2ℓ 용기에 취득하여 밀봉 멸균한 뒤 냉장 보관한 다음 본 발명의 건강음료 조성물 제조에 사용한다. The above components were mixed according to a conventional health drink manufacturing method, and the mixture was heated at 85 DEG C for about 1 hour with stirring, and the solution thus prepared was filtered to obtain a sterilized 2-liter container, which was sealed and sterilized, ≪ / RTI >
상기 조성비는 비교적 기호음료에 적합한 성분을 바람직한 실시예로 혼합 조성하였지만, 수요계층, 수요국가, 사용용도 등 지역적, 민족적 기호도에 따라서 그 배합비를 임의로 변형 실시하여도 무방하다.
Although the composition ratio is a mixture of the components suitable for the preferred beverage as a preferred embodiment, the blending ratio may be arbitrarily varied according to the regional and national preferences such as the demand level, the demanding country, and the intended use.
Claims (12)
A pharmaceutical composition for the prevention and treatment of neuronal cell protection and depression comprising ginseng seed extract as an active ingredient.
상기 인삼씨 추출물은 인삼씨의 물, 유기용매 또는 이들의 혼합물의 추출물인 약제학적 조성물.
The method according to claim 1,
Wherein the ginseng seed extract is an extract of ginseng seeds, an organic solvent or a mixture thereof.
상기 유기용매는 저급 알코올, 헥산, 아세톤, 에틸 아세테이트, 클로로포름, 및 디에틸에테르로 이루어진 군으로부터 선택된 하나 이상의 용매인 약제학적 조성물.
3. The method of claim 2,
Wherein the organic solvent is at least one solvent selected from the group consisting of lower alcohols, hexane, acetone, ethyl acetate, chloroform, and diethyl ether.
상기 인삼씨 추출물은 인삼씨의 저급 알코올 추출물인 약제학적 조성물.
The method according to claim 1,
Wherein the ginseng seed extract is a lower alcohol extract of ginseng seed.
상기 인삼씨 추출물은 인삼씨의 에탄올 추출물인 약제학적 조성물.
The method according to claim 1,
Wherein the ginseng seed extract is an ethanol extract of ginseng seed.
상기 인삼씨 추출물은 인삼씨의 헥산 추출물인 약제학적 조성물.
The method according to claim 1,
Wherein the ginseng seed extract is a hexane extract of ginseng seed.
The present invention relates to a food composition for preventing and ameliorating neuronal cell protection and depression comprising ginseng seed extract as an active ingredient.
상기 인삼씨 추출물은 인삼씨의 물, 유기용매 또는 이들의 혼합물의 추출물인 식품 조성물.
8. The method of claim 7,
Wherein the ginseng seed extract is an extract of ginseng seeds, an organic solvent or a mixture thereof.
상기 유기용매는 저급 알코올, 헥산, 아세톤, 에틸 아세테이트, 클로로포름, 및 디에틸에테르로 이루어진 군으로부터 선택된 하나 이상의 용매인 식품 조성물.
9. The method of claim 8,
Wherein the organic solvent is at least one solvent selected from the group consisting of lower alcohols, hexane, acetone, ethyl acetate, chloroform, and diethyl ether.
상기 인삼씨 추출물은 인삼씨의 저급 알코올 추출물인 식품 조성물.
8. The method of claim 7,
Wherein the ginseng seed extract is a lower alcohol extract of ginseng seed.
상기 인삼씨 추출물은 인삼씨의 에탄올 추출물인 식품 조성물.
8. The method of claim 7,
Wherein the ginseng seed extract is an ethanol extract of ginseng seed.
상기 인삼씨 추출물은 인삼씨의 헥산 추출물인 식품 조성물.
8. The method of claim 7,
Wherein the ginseng seed extract is a hexane extract of ginseng seed.
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Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
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WO2018101630A1 (en) * | 2016-12-01 | 2018-06-07 | 재단법인 전남생물산업진흥원 | Health functional food composition for preventing and alleviating depression, containing vaccinium bracteatum thunb. fruit extract |
KR20230100697A (en) | 2021-12-28 | 2023-07-05 | 건국대학교 글로컬산학협력단 | Composition for improving neuroinflammatory disease or memory containing ginseng flower extract |
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Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
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WO2018101630A1 (en) * | 2016-12-01 | 2018-06-07 | 재단법인 전남생물산업진흥원 | Health functional food composition for preventing and alleviating depression, containing vaccinium bracteatum thunb. fruit extract |
CN110113957A (en) * | 2016-12-01 | 2019-08-09 | 财团法人全南生物产业振兴院 | The health functional food composition for being used to prevent and improve depression comprising blueberry fruit extract |
US10925914B2 (en) | 2016-12-01 | 2021-02-23 | Jeonnam Bioindustry Foundation | Method for alleviating depression using a health functional food containing Vaccinium bracteatum Thunb fruit extract |
KR20230100697A (en) | 2021-12-28 | 2023-07-05 | 건국대학교 글로컬산학협력단 | Composition for improving neuroinflammatory disease or memory containing ginseng flower extract |
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