KR101785495B1 - Composition comprising Chrisanthemum indicum extract or fraction for treating, improving or preventing obesity or obesity-related disease - Google Patents
Composition comprising Chrisanthemum indicum extract or fraction for treating, improving or preventing obesity or obesity-related disease Download PDFInfo
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- KR101785495B1 KR101785495B1 KR1020170078338A KR20170078338A KR101785495B1 KR 101785495 B1 KR101785495 B1 KR 101785495B1 KR 1020170078338 A KR1020170078338 A KR 1020170078338A KR 20170078338 A KR20170078338 A KR 20170078338A KR 101785495 B1 KR101785495 B1 KR 101785495B1
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- Prior art keywords
- obesity
- extract
- fraction
- composition
- ethyl acetate
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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)
- A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
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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
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
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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
- A23V2200/332—Promoters of weight control and weight loss
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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
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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
- A61K2236/35—Extraction with lipophilic solvents, e.g. Hexane or petrol ether
Abstract
본 발명은 감국 추출물 또는 분획물을 유효성분으로 포함하는 비만, 비만 관련 질환 또는 합병증의 예방, 개선 또는 치료용 조성물에 관한 것으로, 보다 상세하게는 비만 발현 인자인 PPAR-g 및 C/EBP pathway 단백질 발현량을 감소시키고, 지방전구세포에서 지방세포로의 분화를 억제하며, 혈중 렙틴(leptin) 발현량을 감소시키고 아디포넥틴(adiponectin) 발현량을 증가시켜 우수한 항비만 효능 뿐 아니라 간 지질 침착 감소 효능을 가지는 감국 추출물 또는 분획물을 유효성분으로 포함하는 비만, 비만 관련 질환 또는 합병증의 예방, 개선 또는 치료용 조성물에 관한 것이다.The present invention relates to a composition for preventing, ameliorating or treating obesity, obesity-related diseases or complications comprising extracts or fractions thereof as an active ingredient, and more particularly to a composition for preventing, ameliorating or treating obesity, (Leptin) and increase the adiponectin expression level, thereby reducing the lipid peroxidation effect, as well as the anti-obesity effect. In addition, And a composition for preventing, ameliorating or treating obesity, obesity-related diseases or complications comprising an extract or fraction as an active ingredient.
Description
본 발명은 감국 추출물 또는 분획물을 유효성분으로 포함하는 비만, 비만 관련 질환 또는 합병증의 예방, 개선 또는 치료용 조성물에 관한 것으로, 보다 상세하게는 우수한 항비만 효능 뿐 아니라 지질 침착 감소 효능을 가지는 감국 추출물 또는 분획물을 유효성분으로 포함하는 비만, 비만 관련 질환 또는 합병증의 예방, 개선 또는 치료용 조성물에 관한 것이다.The present invention relates to a composition for preventing, ameliorating or treating obesity, obesity-related diseases or complications comprising extracts or fractions thereof as an active ingredient. More particularly, the present invention relates to a composition for preventing, ameliorating or treating obesity, Or fractions thereof as an active ingredient for the prevention, amelioration or treatment of obesity, obesity-related diseases or complications.
식생활 환경의 향상과 더불어 영양 섭취가 양호해지면서 사람들의 평균 수명이 연장되고 있으나, 식생활의 서구화, 음식의 과다 섭취, 육체적 운동 부족 등으로 말미암아 비만 환자가 매년 급속히 증가되고 있다. As the dietary environment improves, nutritional intake improves and the average life span of people is prolonged. However, obesity patients are rapidly increasing every year due to westernization of diet, excessive intake of food, and lack of physical exercise.
비만은 주요 성인병들의 위험요소(risk factor)로, 고혈압, 당뇨, 동맥경화증, 뇌졸중, 심장마비, 각종 종양 등과 같은 성인병의 발생에 관여하고 병의 진행을 촉진시키기도 하는데, 비만은 단순히 외모상의 문제만이 아니라 건강에 직결되는 중대한 문제가 아닐 수 없다.Obesity is a risk factor for major adult diseases. It is involved in the development of diseases such as hypertension, diabetes, arteriosclerosis, stroke, heart attack and various tumors and promotes disease progression. This is a serious problem directly linked to health.
이러한 비만의 예방은 현 상태의 식사량은 유지하면서 운동량을 늘리는 것이 중요하며, 비만이 되었을 경우에는 원인을 파악하고 거기에 맞는 적절한 식이요법을 통하여 적정 체중을 유지하면서, 신체가 정상적인 신진대사를 할 수 있도록 하는 것이 바람직하다.It is important to prevent this obesity by increasing the amount of exercise while maintaining the amount of food in the current state. When obesity becomes a cause, it is necessary to identify the cause and maintain proper body weight through proper dieting .
비만이 현대사회의 문제로 대두되면서, 다이어트란 말은 현대를 살아가는 많은 사람들에게 관심을 끌고 있다. 비만자들이 체중감량에 기울이는 관심과 노력이 높다는 점을 이용하여 지금까지 소개된 수많은 다이어트 방법들이 있는데, 단식 및 금식, 야채효소, 지방 흡인술, 설사약, 이뇨제 등이 있다.As obesity has become a problem of modern society, the word diet is attracting many people living in modern times. There are a number of diet methods that have been introduced so far, including fasting and fasting, vegetable enzymes, liposuction, laxatives, diuretics, etc., because of the high interest and effort of obese people to lose weight.
그러나, 다이어트에 대한 정확하고 과학적인 원인 파악 및 인체 신진대사의 기전과 영양 생리학적으로의 접근은 등한시한 채, 무분별하게 체중감량의 효과에만 치중함으로써, 영양소 섭취의 불균형을 초래하게 되어 신진대사가 정상적으로 이루어지지 못한 문제점이 있다.However, the accurate and scientific understanding of diet and the mechanism of human metabolism and the approach to nutrition physiology are indifferent to the effects of weight loss alone, resulting in imbalance of nutrient intake, There is a problem that it is not normally done.
한편, 체중감량을 위한 방법으로 암페타민 유도제 등 식욕억제제를 이용한 약물요법이 있는데, 이러한 약물요법은 식욕억제 능력이 지속되지 못하고 일시적인 작용으로 두통, 불면증, 혈압상승, 초조, 긴장감, 환각증세, 현기증, 시력 저하 등의 부작용을 유발시키는 문제점이 있다.In addition, there is a drug therapy using an appetite suppressing agent such as an amphetamine inducing agent as a method for weight loss. However, such a pharmacotherapy does not maintain the appetite suppressing ability and temporarily causes a headache, insomnia, blood pressure rise, irritability, tension, hallucination, There is a problem that side effects such as decreased visual acuity are caused.
또한 이뇨제를 사용하여 체중을 감량 및 조절하는 경우도 있으나, 이 방법 또한 신장에 대한 중독성과 심장마비, 구토 등을 수반하는 부작용을 일으키는 문제점이 있다. In addition, diuretics may be used to lose weight and control, but this method also has side effects that lead to addiction to the kidneys, heart attack, and vomiting.
이 외에도 뇌의 중추에 작용하여 식욕을 억제하게 하는 중추성 식욕 억제제가 있는데, 이는 감량효과는 뛰어나지만 어느 정도 시간이 지나면 약에 대한 내성이 생겨서 이후에는 몸무게가 거의 줄지 않으며, 두통, 불면증, 어지러움 등의 부작용을 초래하는 경우가 많다. In addition, there is a central appetite suppressant that acts on the brain's central nervous system to inhibit appetite, which is excellent in weight loss, but after a certain period of time, resistance to the drug has developed and thereafter the body weight is almost unchanged, headache, insomnia, dizziness And the like.
현재 비만치료제로 널리 사용되는 식욕억제제의 경우, 뇌의 시상하부에 작용하여 식욕억제로 인한 체중 감량 효과를 나타내는 작용기전을 가지고 있으며, 이들 대부분은 중추 신경 흥분을 유발시켜 이의 작용을 유발하는 것으로 알려져 있다. 국내에서 대표적인 식욕억제제로 사용중인 시부트라민(Sibutramine, 상품명; 리덕틸)은 식욕 조절에 작용하는 신경호르몬인 세로토닌(Serotonin)과 noradrenaline의 재흡수를 동시에 억제시켜 식욕을 떨어뜨리는 약물이다. 그러나 이들 대부분의 식욕억제제의 경우, 교감 신경을 흥분시켜 혈압이나 심박출량이 증가하게 되고, 결과적으로 심혈관계 환자에게 이들 약물 복용은 금기시 되고 있다. 또한 일부 약물에서는 정신적, 신체적 의존성이 있는 것으로 알려져 있다.Currently, appetite suppressants, which are widely used for obesity treatment, have a mechanism of action that acts on the hypothalamus of the brain, resulting in loss of weight due to appetite suppression. Most of them induce central nervous excitement and induce its action have. Sibutramine (Reductil), a typical appetite suppressant in Korea, is a drug that decreases the appetite by simultaneously inhibiting the reuptake of noradrenaline and serotonin, the neurohormones that control appetite. However, in most of these appetite suppressants, sympathetic nerves are excited to increase blood pressure and cardiac output, and consequently these medications are contraindicated in cardiovascular patients. In addition, some drugs are known to have psychological and physical dependence.
따라서, 인위적인 방법으로 합성된 치료제의 형태가 아닌 종래에 우리가 섭취하고 있는 생약재 등을 식품의 형태로 공급할 수 있는 다이어트 조성물이 개발될 필요가 있다고 할 수 있다.Therefore, it is necessary to develop a diet composition capable of supplying, in the form of food, the herbal medicines and the like which are conventionally consumed, rather than a form of therapeutic agent synthesized by an artificial method.
한편, 감국은 국화과(Compositae)에 속하는 다년생 초본으로 차로 음용해 왔고, 한방에서는 그 꽃을 현기증, 해열, 염증, 고혈압 및 호흡계 질환에 사용해 왔다. 감국의 주성분으로는 플라보노이드 화합물, 테르페노이드 화합물, 페놀성 화합물 등이 알려져 있다. 감국의 생리활성 연구로는 항균활성, 항바이러스활성, 항산화활성, 면역조절활성 등이 있는 것으로 보고되고 있다. 상기와 같이 감국의 다양한 약리효과에 대해 알려져 있지만, 구체적으로 감국의 추출물 및 분획물이 어느 질병에 효과가 있는지에 대한 연구는 미진한 상태다.On the other hand, the munguk has been drinking tea as a perennial herb belonging to the Compositae and has been used in oriental medicine for dizziness, fever, inflammation, hypertension and respiratory diseases. As the main components of cuttlefish, flavonoid compounds, terpenoid compounds, phenolic compounds and the like are known. Antimicrobial activity, antiviral activity, antioxidant activity, and immunomodulating activity have been reported as the biomass activity studies of the immune system. As described above, various pharmacological effects of Ganoderma lucidum are known, but studies on the effect of extracts and fractions of Ganoderma lucidum on the diseases are insufficient.
상기와 같은 종래기술의 문제점을 해결하고자, 본 발명은 비만 발현 인자인 PPAR-g 및 C/EBP pathway 단백질 발현량을 감소시키고, 지방전구세포에서 지방세포로의 분화를 억제하는 감국 추출물 또는 분획물을 유효성분으로 포함하는 비만, 비만 관련 질환 또는 합병증의 예방, 개선 또는 치료용 조성물을 제공하는 것을 목적으로 한다.In order to solve the problems of the prior art as described above, the present invention provides a method for reducing the expression of PPAR-g and C / EBP pathway proteins, which are obesity inducing factors, and inhibiting the differentiation of adipocytes into adipocytes, And a composition for preventing, ameliorating, or treating obesity, obesity-related diseases or complications, which is contained as a component.
또한 본 발명은 혈중 렙틴(leptin) 발현량을 감소시키고 아디포넥틴(adiponectin) 발현량을 증가시켜 우수한 항비만 효능 뿐 아니라 간 지질 침착 감소 효능을 가지는 감국 추출물 또는 분획물을 유효성분으로 포함하는 비만, 비만 관련 질환 또는 합병증의 예방, 개선 또는 치료용 조성물을 제공하는 것을 목적으로 한다.In addition, the present invention relates to a method for reducing obesity, obesity, and obesity, which comprises, as an active ingredient, an extract or fraction having an effect of decreasing leptin expression in blood and increasing adiponectin expression, It is intended to provide a composition for preventing, ameliorating or treating diseases or complications.
상기 목적을 달성하기 위하여, 본 발명은 감국 추출물 또는 분획물을 유효성분으로 포함하는 비만, 비만 관련 질환 또는 합병증의 예방 또는 치료용 약학 조성물을 제공한다.In order to accomplish the above object, the present invention provides a pharmaceutical composition for preventing or treating obesity, obesity-related diseases or complications, which comprises extract of Cuttlefish or a fraction thereof as an active ingredient.
상기 감국 추출물 또는 분획물은 (a)감국을 물, 탄소수 1 내지 4의 알코올 및 이들의 혼합용매 중 선택된 어느 하나 이상의 용매로 추출하여 감국 추출물을 얻는 단계 및 (b)상기 감국 추출물에 증류수를 가하고 유기용매를 이용하여 순차적으로 분획하여 각 용매 분획물을 얻는 단계로 제조될 수 있다.(B) adding distilled water to the extract, and adding the extract to the extract; and (c) adding the distilled water to the extract to obtain an extract from the extract, wherein the extract or fraction is obtained by extracting the extract with a solvent selected from water, an alcohol having 1 to 4 carbon atoms and a mixed solvent thereof, And sequentially fractionating them using a solvent to obtain respective solvent fractions.
특히, 상기 (a)단계의 탄소수 1 내지 4의 알코올은 메탄올, 에탄올, 프로판올, 이소프로판올 및 부탄올 중 선택된 어느 하나 이상인 것이 바람직하며, 상기 (b)단계의 유기용매는 디클로로메탄, 에틸아세테이트 및 물 중 선택된 어느 하나 이상인 것이 바람직하다.Particularly, it is preferable that the alcohol having 1 to 4 carbon atoms in step (a) is at least one selected from methanol, ethanol, propanol, isopropanol and butanol, and the organic solvent in step (b) is at least one selected from the group consisting of dichloromethane, ethyl acetate, It is preferable that any one or more selected.
상기 감국 추출물 또는 분획물은 이소클로로제닉산(isochlorogenic acid), 다이하이드로시린진(dihydrosyringin), 시린진(syringin), 벤질-β-D-글루코피라노사이드(benzyl-β-D-glucopyranoside, 퀘세틴(quercetin), 메틸-3,4-디-O-카페오일 퀴네이트(methyl 3,4-di-O-caffeoyl-quinate) 및 시나린(cynarine) 중 선택된 어느 하나 이상을 수 있다.The cuttlefish extract or fraction is selected from the group consisting of isochlorogenic acid, dihydrosyringin, syringin, benzyl-beta-D-glucopyranoside, quercetin quercetin, methyl 3,4-di-O-caffeoyl-quinate and cynarine may be used.
상기 감국 추출물 또는 분획물은 조성물 총 중량에 대하여 0.01~95중량%로 포함되는 것이 바람직하다.The cuttlefish extract or fraction is preferably contained in an amount of 0.01 to 95% by weight based on the total weight of the composition.
상기 감국 추출물 또는 분획물은 비만 발현 인자인 PPAR-g 및 C/EBP pathway 단백질 발현량을 감소시키며, 지방전구세포에서 지방세포로의 분화를 억제하고, 혈중 렙틴(leptin)의 발현량을 감소시키고, 아디포넥틴(adiponectin)의 발현량을 증가시킬 수 있다.The extracts or fractions thereof reduce the expression of PPAR-g and C / EBP pathway proteins, which are obesity-inducing factors, inhibit the differentiation into adipocytes from adipose precursor cells, decrease the expression amount of leptin in blood, the amount of adiponectin expressed can be increased.
또한 본 발명은 감국 추출물 또는 분획물을 유효성분으로 포함하는 비만, 비만 관련 질환 또는 합병증의 예방 또는 개선용 식품 조성물을 제공하는 바, 상기 식품 조성물은 건강기능식품, 식품첨가제 또는 식이보조제일 수 있다.Also, the present invention provides a food composition for preventing or ameliorating obesity, obesity-related diseases or complications, which comprises extracts or fractions thereof as an active ingredient, and the food composition may be a health functional food, a food additive or a dietary supplement.
상기 감국 추출물 또는 분획물은 조성물 총 중량에 대하여 0.01~95중량%로 포함되는 것이 바람직하다.The cuttlefish extract or fraction is preferably contained in an amount of 0.01 to 95% by weight based on the total weight of the composition.
본 발명에 따르면 비만 발현 인자인 PPAR-g 및 C/EBP pathway 단백질 발현량을 감소시키고, 지방전구세포에서 지방세포로의 분화를 억제할 수 있으며, 혈중 렙틴(leptin) 발현량을 감소시키고 아디포넥틴(adiponectin) 발현량의 증가를 통해 우수한 항비만 효능 뿐 아니라 간 지질 침착 감소 효능을 나타내어 비만, 비만 관련 질환 또는 합병증의 예방, 개선 또는 치료할 수 있는 효과가 있다.According to the present invention, the expression level of PPAR-g and C / EBP pathway, which are obesity inducers, can be decreased, the differentiation of adipocytes into lipoprotein can be inhibited, the amount of leptin expressed in the blood can be decreased and adiponectin ) Exhibits an excellent anti-obesity effect as well as an effect of reducing hepatic lipid deposition and thus has an effect of preventing, improving or treating obesity, obesity-related diseases or complications.
도 1은 본 발명의 일실시예에 따라 감국 추출물, 분획물 및 7종의 단일 분획물의 분리방법을 나타낸 모식도이다.
도 2는 본 발명의 일실시예에 따라 감국 추출물, 분획물 및 7종의 단일 분획물이 세포생존력에 미치는 영향을 나타낸 도이다.
도 3은 본 발명의 일실시예에 따라 감국 추출물, 분획물 및 7종의 단일 분획물 처리 시 3T3-L1 지방전구세포에서의 지방축적율을 나타낸 도이다.
도 4는 본 발명의 일실시예에 따라 감국 추출물 처리 시 C57BL/6 마우스에서의 랩틴, 아디포넥틴 함량을 나타낸 도이다.
도 5는 본 발명의 일실시예에 따라 감국 에틸아세테이트 분획물 처리 시 C57BL/6 마우스에서의 랩틴, 아디포넥틴 함량을 나타낸 도이다.
도 6은 본 발명의 일실시예에 따라 감국 추출물 처리 시 C57BL/6 마우스의 간에서 PPAR-gamma 및 C/EBPs의 발현량을 나타낸 도이다.
도 7은 본 발명의 일실시예에 따라 감국 에틸아세테이트 분획물 처리 시 C57BL/6 마우스의 간에서 PPAR-gamma 및 C/EBPs의 발현량을 나타낸 도이다.
도 8은 본 발명의 일실시예에 따라 감국 추출물 처리 시 C57BL/6 마우스의 백색 부고환 지방 조직에서 PPAR-gamma 및 C/EBPs의 발현량을 나타낸 도이다.
도 9는 본 발명의 일실시예에 따라 감국 에틸아세테이트 분획물 처리 시 C57BL/6 마우스의 백색 부고환 지방 조직에서 PPAR-gamma 및 C/EBPs의 발현량을 나타낸 도이다.FIG. 1 is a schematic view showing a method for separating Momordicae radix extract, fractions and seven single fractions according to an embodiment of the present invention.
FIG. 2 is a graph showing the effect of ganoderma extract, fraction and seven single fractions on cell viability according to an embodiment of the present invention.
FIG. 3 is a graph showing the fat accumulation rate in 3T3-L1 adipose precursor cells in the case of Acanthopanax senticosus extract, fraction and 7 kinds of single fractions according to an embodiment of the present invention.
FIG. 4 is a graph showing the content of lapatin and adiponectin in C57BL / 6 mice in the treatment of hamster extract according to an embodiment of the present invention.
FIG. 5 is a graph showing the content of lapatin and adiponectin in C57BL / 6 mice in the treatment of muffin ethyl acetate fraction according to one embodiment of the present invention.
FIG. 6 is a graph showing the expression levels of PPAR-gamma and C / EBPs in the liver of C57BL / 6 mice in the treatment of hamster extract according to an embodiment of the present invention.
FIG. 7 is a graph showing the expression levels of PPAR-gamma and C / EBPs in the liver of C57BL / 6 mice in the treatment with acetic acid ethyl acetate fraction according to an embodiment of the present invention.
FIG. 8 is a graph showing the expression levels of PPAR-gamma and C / EBPs in white epididymal adipose tissue of C57BL / 6 mice in the treatment of hamster extract according to an embodiment of the present invention.
FIG. 9 is a graph showing the expression levels of PPAR-gamma and C / EBPs in white epidiphilic adipose tissue of C57BL / 6 mice in the treatment of acetic acid ethyl acetate fraction according to an embodiment of the present invention.
이하 본 발명을 상세히 설명한다. Hereinafter, the present invention will be described in detail.
본 발명은 감국 추출물 또는 분획물이 지방전구세포에서 지방세포로 활성화되는 과정에서 지방 전구세포에서 지질 축적을 억제하고, 지방세포 분화 과정에서 C/EBP-alpha, C/EBP-beta 및 C/EBP-gamma 및 PPAR-gamma와 같은 지방세포 분화의 초,중기 전사인자들의 단백질 발현을 유의적으로 감소시킴을 확인하였다.C / EBP-alpha, C / EBP-beta, and C / EBP-alpha in the adipocyte differentiation process inhibits lipid accumulation in adipose precursor cells during the activation of adipocyte extract or fraction from fat precursor cells to adipocytes. gamma and PPAR-gamma, respectively, in the adipocyte differentiation.
따라서 본 발명자들은 새로운 약물을 개발하기 위해 감국 추출물 또는 분획물에 대한 연구를 수행하여, 감국 추출물 또는 분획물이 고지방 식이로 유도된 비만에서의 우수한 효과가 있음을 확인하였고, 이를 토대로 본 발명을 완성하였다. Accordingly, the inventors of the present invention conducted studies on cuttlefish extract or fractions to develop new drugs, and confirmed that the cuttlefish extract or fraction had excellent effects in a high fat diet-induced obesity, and completed the present invention on this basis.
이러한 본 발명의 비만, 비만 관련 질환 또는 합병증의 예방, 개선 또는 치료용 조성물은 감국 추출물 또는 분획물을 유효성분으로 포함한다.The composition for preventing, ameliorating or treating the obesity, obesity-related diseases or complications of the present invention comprises extracts or fractions thereof as an active ingredient.
상기 감국(Chrysanthemum indicum L.) 추출물 또는 분획물은 감국의 다양한 부위로부터 추출될 수 있으며, 바람직하게는 감국의 꽃, 잎, 줄기, 뿌리 또는 전초로부터 추출되는 것이며, 더욱 바람직하게는 감국의 꽃 또는 잎으로부터 추출되는 것이며, 가장 바람직하게는 감국의 꽃으로부터 추출되는 것이다.The extract or fraction of Chrysanthemum indicum L. can be extracted from various parts of the cuttlefish, preferably extracted from flowers, leaves, stems, roots or outposts of cuttlefish, more preferably from flowers or leaves of cuttlefish , And most preferably from a flower of a cuttlefish.
상기 감국 추출물 또는 분획물은 당업계에 공지된 추출, 분리 및 분획하는 방법을 사용하여 천연으로부터 추출, 분리 및 분획하여 수득한 것을 사용할 수 있다. 본 발명에서 정의된 '추출물'은 적절한 용매를 이용하여 감국으로부터 추출 처리에 의해 얻어지는 것이며, 예를 들어 감국의 조추출물, 극성용매 가용 추출물 또는 비극성용매 가용 추출물을 모두 포함한다. The cuttlefish extract or fraction can be obtained by extracting, isolating and fractionating from the nature using a method of extraction, separation and fractionation known in the art. The 'extract' defined in the present invention is obtained by extraction treatment from red ginseng using an appropriate solvent and includes, for example, crude extract, polar solvent-soluble extract or non-polar solvent-soluble extract of red ginseng.
상기 감국 추출물은 다양한 추출용매와 추출방법에 따라 추출될 수 있으며, 감국으로부터 추출물 또는 분획물을 추출하기 위한 적절한 용매로는 약학적으로 허용되는 유기용매라면 어느 것을 사용해도 무방하며, 물 또는 유기용매를 사용할 수 있으며, 이에 제한되지는 않는다. 예를 들어, 상기 용매로는 물, 메탄올(methanol), 에탄올(ethanol), 프로판올(propanol), 이소프로판올(isopropanol), 부탄올(butanol) 등의 탄소수 1 내지 4의 알코올 등을 단독으로 또는 2종 이상 혼합하여 사용할 수 있다. 특히, 상기 용매로는 메탄올 또는 에탄올(주정)을 사용하는 것이 바람직하며, 특히 에탄올(주정)을 사용하는 것이 바람직하다.The extract can be extracted according to various extraction solvents and extraction methods, and any suitable solvent for extracting the extract or fractions from the extract can be any pharmaceutically acceptable organic solvent, and water or an organic solvent But is not limited thereto. Examples of the solvent include water, alcohols having 1 to 4 carbon atoms such as methanol, ethanol, propanol, isopropanol, and butanol, etc., Can be mixed and used. Particularly, as the solvent, methanol or ethanol (alcohol) is preferably used, and ethanol (alcohol) is particularly preferably used.
상기 추출 온도는 50~100℃인 것이 바람직하다. 또한 추출방법으로는 열수추출법, 냉침추출법, 환류냉각추출법, 용매추출법, 수증기증류법, 초음파추출법, 용출법, 압착법 등의 방법이 사용될 수 있으며, 특히 열수추출법 또는 환류냉각추출법을 사용하는 것이 더욱 바람직하다. The extraction temperature is preferably 50 to 100 ° C. As the extraction method, methods such as hot water extraction method, cold extraction method, reflux cooling extraction method, solvent extraction method, steam distillation method, ultrasonic extraction method, elution method and compression method can be used and more preferred is the use of hot water extraction method or reflux cooling extraction method Do.
또한 상기 감국 분획물은 전술한 바와 같이 추출된 감국 추출물을 유기용매를 비극성에서 극성으로 분획하여 각 용매 분획물을 얻을 수 있다. In addition, the gum-like fractions can be obtained by fractionating the organic extract from non-polar to polar fractions of the gum extract obtained as described above.
상기 감국 분획물을 분획하기 위한 적절한 용매로는 물, 에탄올, 메탄올, 헥산, 클로로포름, 디클로로메탄, 에틸아세테이트, 부탄올 또는 이들의 혼합용매일 수 있으며, 특히 물을 가하고, 디클로로메탄 및 에틸아세테이트을 이용하여 순차적으로 분획하여 얻어지는 분획물인 것이 좋다. 특히, 물 분획물과 에틸아세테이트 분획물의 경우 다른 분획물에 비해 항비만 활성이 현저히 뛰어나기 때문에 본 발명의 감국 분획물은 물 분획물, 에틸아세테이트 분획물 또는 이들의 혼합물인 것이 더욱 바람직하다.Examples of suitable solvents for fractionation of the gut fractions include water, ethanol, methanol, hexane, chloroform, dichloromethane, ethylacetate, butanol or mixtures thereof. Particularly, water is added, and dichloromethane and ethyl acetate And the like. Particularly, the water fraction and the ethyl acetate fraction are more excellent in anti-obesity activity than the other fractions. Therefore, the water-reducing fraction of the present invention is more preferably a water fraction, an ethyl acetate fraction or a mixture thereof.
상기와 같이 물 또는 유기용매를 이용하여 추출물을 얻은 이후에는 당업계에서 알려진 통상의 방법으로 상온에서 냉침, 가열 및 여과하여 액상물을 얻을 수 있으며, 또는 추가로 용매를 증발, 분무건조 또는 동결건조할 수도 있다. After the extract is obtained using water or an organic solvent as described above, a liquid material can be obtained by freezing, heating and filtering at room temperature by a conventional method known in the art, or a liquid material can be obtained by further evaporating, spray drying or freeze- You may.
또한 본 발명의 조성물에 유효성분으로 포함되는 감국 추출물 또는 분획물은 전술한 바와 같이 추출 및 분획된 추출물이나 분획물을 감압 증류 및 동결 건조 또는 분무 건조 등과 같은 추가적인 과정에 의해 분말 상태로 제조할 수도 있다. 또한 상기 추출물 또는 분획물을 실리카겔 컬럼 크로마토그래피(silica gel column chromatography), 박층크로마토그래피(thin layer chromatography), 고성능 액체 크로마토그래피(high performance liquid chromatography) 등과 같은 다양한 크로마토그래피를 이용하여 추가로 정제된 분획으로도 얻을 수 있다.In addition, the gum extract or fraction contained as an active ingredient in the composition of the present invention may be prepared in powder form by an additional process such as vacuum distillation, freeze-drying, spray-drying, and the like, after extracting and fractionating the extract or fraction as described above. The extract or fraction may be further purified by further chromatography using various chromatographies such as silica gel column chromatography, thin layer chromatography, high performance liquid chromatography and the like Can be obtained.
따라서 본 발명에서 사용되는 감국 추출물 및 분획물은 추출, 분획 또는 정제의 각 단계에서 얻어지는 모든 추출물, 분획물 및 정제물, 그들의 희석액, 농축액 또는 건조물을 모두 포함하는 개념이다.Therefore, the cuttlefish extract and fractions to be used in the present invention include all the extracts, fractions and tablets obtained in each step of extraction, fractionation or purification, their diluted solutions, concentrates or dried products.
상기와 같이 추출 또는 분획한 본 발명의 감국 추출물 또는 분획물은 고지방 식이로 유도된 마우스 모델에서 우수한 항비만 효과를 가지며, 3T3-L1 지방 전구 세포에서 IBMX, 인슐린(insulin) 및 덱사메타손(dexamethasone)을 이용하여 분화를 유도하였을 때 지질 축적 억제를 하여 우수한 항비만 효과를 가진다. 특히, 본 발명의 유효성분인 7개의 단일성분의 경우 더욱 우수한 항비만 효과를 가진다.The extract or fraction of the extract of the present invention, which has been extracted or fractionated as described above, has an excellent anti-obesity effect in a mouse model derived from a high fat diet and can be obtained by using IBMX, insulin and dexamethasone in 3T3-L1 lipogenic precursor cells Induced lipid accumulation, and thus has an excellent anti-obesity effect. In particular, the seven single components of the present invention have an excellent anti-obesity effect.
상기 7개의 단일성분은 이소클로로제닉산(isochlorogenic acid, 하기 화학식 1), 다이하이드로시린진(dihydrosyringin, 하기 화학식 2), 시린진(syringin, 하기 화학식 3), 벤질-β-D-글루코피라노사이드(benzyl-β-D-glucopyranoside, 하기 화학식 4), 퀘세틴(quercetin, 하기 화학식 5), 메틸-3,4-디-O-카페오일 퀴네이트(methyl 3,4-di-O-caffeoyl-quinate, 하기 화학식 6) 및 시나린(cynarine, 하기 화학식 7)로 표시되는 화합물이다.The seven single components are selected from the group consisting of isochlorogenic acid (1), dihydrosyringin (2), syringin (3), benzyl- beta -D-glucopyranosyl Di-O-caffeoyl, quercetin, methyl-3,4-di-O-caffeoyl, benzyl-β-D-glucopyranoside, -quinate, the following formula (6), and a cynarine (7).
[화학식 1][Chemical Formula 1]
[화학식 2](2)
[화학식 3](3)
[화학식 4][Chemical Formula 4]
[화학식 5][Chemical Formula 5]
[화학식 6][Chemical Formula 6]
[화학식 7](7)
본 발명에서는 상기와 같이 추출 또는 분획한 본 발명의 감국 추출물 또는 분획물, 특히 전술한 7종의 감국 추출물 또는 분획물을 이용하여 3T3-L1 지방전구세포가 지방세포로의 분화를 억제함을 세포질 내의 중성지방을 확인하여 밝혀내었다. 또한 본 발명의 감국 추출물 또는 분획물이 지방세포 분화 과정에서 C/EBP-alpha, C/EBP-beta, C/EBP-gamma 및 PPAR-gamma와 같은 지방세포 분화의 초,중기 전사인자들의 단백질 발현을 유의적으로 감소시키고, 혈중 렙틴(leptin) 발현량을 감소, 아디포넥틴(adiponectin) 발현량의 증가시킴을 확인하였다.In the present invention, 3T3-L1 adipocyte precursor cells inhibit the differentiation into adipocytes by using the Admutagen Extract or the fraction of the present invention extracted or fractionated as described above, particularly 7 kinds of Admutagen Extracts or Fractions described above. . In addition, the present invention provides a method for inhibiting the expression of proteins in early and midterm transcription factors of adipocyte differentiation such as C / EBP-alpha, C / EBP-beta, C / EBP-gamma and PPAR- (Leptin) and adiponectin (adiponectin) expression in the blood, respectively.
또한 본 발명에서는 실험동물모델을 이용하여 정상식이를 섭취하는 대조군 및 고지방 식이와 동시에 감국 추출물 및 분획물을 섭취한 실험군의 체중 및 체중증가량 변화를 측정하여 체중 및 체중 증가량에 미치는 영향을 확인하였으며, 그 결과 본 발명의 유효성분인 감국의 추출물 또는 분획물이 체중 및 체중 증가율을 유의성 있게 감소시킴을 확인하였다. In the present invention, the effect of body weight and weight gain on the increase in body weight and weight gain of the control group consuming the normal diet and the high fat diet and the control group consuming the hamsters extract and fractions at the same time was confirmed by the experimental animal model. As a result, it was confirmed that the extract or fraction of T. ganoderma, an active ingredient of the present invention, significantly decreased body weight and body weight gain.
따라서 본 발명의 감국 추출물 또는 분획물은 비만, 비만 관련 질환 또는 합병증의 예방, 치료 및 개선에 유용한 약품 또는 식품으로 이용될 수 있다. 또한 본 발명의 조성물은 인간 뿐 아니라 다른 동물의 비만이나 비만 관련 질환, 비만으로 인한 합병증의 예방, 치료 및 개선을 위해 사용될 수 있음은 물론이다.Therefore, the extract or fraction thereof of the present invention can be used as a drug or food useful for prevention, treatment and improvement of obesity, obesity-related diseases or complications. In addition, the composition of the present invention may be used for prevention, treatment, and improvement of obesity, obesity-related diseases, and obesity-related complications of humans as well as other animals.
본 발명의 조성물은 신체 각 부위의 비만 또는 복부비만의 예방, 개선 또는 치료를 위하여도 사용될 수 있으며, 대상 복부비만으로서는 장시간 의자에 앉아있는 생활을 하거나, 운동부족, 술(알코올) 섭취, 스트레스 등에 의한 복부비만을 포함하며, 이에 제한되는 것은 아니다.The composition of the present invention can also be used for prevention, improvement or treatment of obesity or abdominal obesity in each part of the body. As a target abdominal obesity, it can be used for a long time sitting in a chair, a lack of exercise, alcohol ≪ / RTI > abdominal obesity due to < RTI ID = 0.0 >
또한 비만으로 인한 합병증으로는 중성지질, 콜레스테롤, 저밀도 지질의 혈중농도 상승에 기인한 질병을 포함하며, 이에 제한되지 않는다. 예를 들어, 비만으로 인한 합병증으로는 대사증후군(내장 지방 증후군, 대사 이상 증후군 등), 고트리글리세라이드 혈증, 저HDL혈증, 협심증, 심근경색, 성기능부전증, 수면무호흡증, 월경전 증후군, 스트레스성 뇨실금을 포함하는 뇨실금, 과행동장애, 만성 피로 증후군, 골관절염, 체중 증가와 관련된 암, 기립성 저혈압, 폐고혈압, 월경장애, 당뇨병, 고혈압, 손상된 내당력, 관상동맥혈전증, 졸증, 우울증, 불안증, 정신병, 지연성 운동장애, 약물중독, 약물 남용, 인지장애, 알츠하이머병, 뇌허혈, 강박성 행동, 공황발작, 사회공포증, 대식증, 아테롬성동맥경화증, 담석증과 같은 담낭 질병, 식욕부진, 다낭성 난소 질환과 같은 생식장애, 감염, 정맥류성 정맥, 표피증식 및 습진과 같은 피부병, 인슐린 저항성, 만성 동맥폐색증, 정형외과적 상해, 혈전색전증, 심장질환, 비뇨기질환, 지질증후군, 과혈당증, 스트레스 등이 있으며, 이에 한정되는 것은 아니다. Also, complications due to obesity include, but are not limited to, diseases caused by elevated blood levels of neutral lipids, cholesterol, and low density lipids. For example, complications due to obesity include metabolic syndrome (visceral fat syndrome, metabolic syndrome, etc.), hypertriglyceridemia, hypohidrosis, angina pectoris, myocardial infarction, hypogonadism, sleep apnea syndrome, premenstrual syndrome, Hyperlipidemia, diabetes mellitus, hypertension, impaired glucose tolerance, coronary artery thrombosis, diaphoresis, depression, anxiety, hyperlipidemia, hypertension, diabetes mellitus, , Anorexia nervosa, polycystic ovarian disease, atherosclerosis, atherosclerosis, atherosclerosis, gallbladder disease such as atherosclerosis, gallstone disease, anorexia nervosa, anorexia nervosa, Dermatological conditions such as reproductive disorders, infections, varicose veins, epidermal hyperplasia and eczema, insulin resistance, chronic arterial occlusion, orthopedic injuries, thromboembolism , Heart disease, urinary disease, lipid syndrome, hyperglycemia, stress, and the like.
이에 본 발명음 감국 추출물 또는 분획물을 유효성분으로 포함하는 비만, 비만 관련 질환 또는 합병증의 예방 또는 치료용 약학 조성물을 제공한다.Accordingly, the present invention provides a pharmaceutical composition for preventing or treating obesity, obesity-related diseases or complications comprising the extract or fractions of the present invention as an active ingredient.
상기 감국 추출물 또는 분획물은 약학 조성물 총 중량에 대하여 0.01~95중량%로 포함되는 것이 바람직하며, 더욱 바람직하게는 1~80중량%로 포함되는 것이다. 그 함량이 0.01중량% 미만일 경우에는 복용 효율성이 떨어질 수 있으며, 95중량%를 초과할 경우에는 제형화의 어려움이 있을 수 있다.The gut extract or fraction is preferably contained in an amount of 0.01 to 95% by weight, more preferably 1 to 80% by weight, based on the total weight of the pharmaceutical composition. If the content is less than 0.01% by weight, the efficiency of taking may be lowered. If the content is more than 95% by weight, formulation may be difficult.
본 발명의 조성물은 약학 조성물의 제조에 통상적으로 사용하는 적절한 담체, 부형제 및 희석제를 더 포함할 수 있다. 또한 통상의 방법에 따라 산제, 과립제, 정제, 캡슐제, 현탁액, 에멀젼, 시럽, 에어로졸 등의 경구형 제형, 외용제, 좌제 및 멸균 주사용액의 형태로 제형화하여 사용될 수 있다. 당해 기술 분야에 알려진 적합한 제제는 문헌(Remington's Pharmaceutical Science, 최근, Mack Publishing Company, Easton PA)에 개시되어 있는 것을 사용하는 것이 바람직하다. 포함될 수 있는 담체, 부형제 및 희석제로는 락토오스, 덱스트로오스, 수크로오스, 소르비톨, 만니톨, 자일리톨, 에리스리톨, 말티톨, 전분, 아카시아 고무, 알지네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실리케이트, 셀룰로오스, 메틸 셀룰로오스, 미정질 셀룰로오스, 폴리비닐 피롤리돈, 물, 메틸히드록시 벤조에이트, 프로필히드록시 벤조에이트, 탈크, 마그네슘 스테아레이트, 광물유 등이 있다. 상기 조성물을 제제화할 경우에는 보통 사용하는 충진제, 증량제, 결합제, 습윤제, 붕해제, 계면활성제 등의 희석제 또는 부형제를 사용하여 조제된다. 경구투여를 위한 고형제제에는 정제, 환제, 산제, 과립제, 캡슐제 등이 포함되며, 이러한 고형제제는 상기 조성물에 적어도 하나 이상의 부형제, 예를 들면 전분, 칼슘 카보네이트(calcium carbonate), 수크로오스, 락토오스, 젤라틴 등을 섞어 조제된다. 또한 단순한 부형제 이외에 마그네슘 스테아레이트, 탈크 같은 윤활제들도 사용된다. 경구를 위한 액상 제제로는 현탁제, 내용액제, 유제, 시럽제 등이 해당되는데 흔히 사용되는 단순 희석제인 물, 리퀴드 파라핀 이외에 여러 가지 부형제, 예를 들면 습윤제, 감미제, 방향제, 보존제 등이 포함될 수 있다. 비경구 투여를 위한 제제에는 멸균된 수용액, 비수성용제, 현탁제, 유제, 동결건조 제제, 좌제 등이 포함된다. 비수성용제, 현탁제로는 프로필렌글리콜(propylene glycol), 폴리에틸렌 글리콜, 올리브 오일과 같은 식물성 기름, 에틸올레이트와 같은 주사 가능한 에스테르 등이 사용될 수 있다. 좌제의 기제로는 위텝솔(witepsol), 마크로골, 트윈(tween) 61, 카카오지, 라우린지, 글리세로제라틴 등이 사용될 수 있다. The compositions of the present invention may further comprise suitable carriers, excipients and diluents conventionally used in the manufacture of pharmaceutical compositions. In addition, it can be formulated in the form of powders, granules, tablets, capsules, suspensions, emulsions, oral preparations such as syrups and aerosols, external preparations, suppositories and sterilized injection solutions according to a conventional method. Suitable formulations known in the art are preferably those as disclosed in Remington ' s Pharmaceutical Science, recently, Mack Publishing Company, Easton PA. Examples of carriers, excipients and diluents which may be included include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methylcellulose, Cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, mineral oil and the like. When the composition is formulated, it is prepared using a diluent such as a filler, an extender, a binder, a wetting agent, a disintegrant, a surfactant, or an excipient usually used. Solid formulations for oral administration include tablets, pills, powders, granules, capsules and the like, which may contain at least one excipient such as starch, calcium carbonate, sucrose, lactose, Gelatin and the like. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Examples of the liquid preparation for oral use include suspensions, solutions, emulsions, and syrups. In addition to water and liquid paraffin, simple diluents commonly used, various excipients such as wetting agents, sweeteners, fragrances, preservatives and the like may be included . Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, suppositories, and the like. Examples of the suspending agent include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like. Examples of the suppository base include witepsol, macrogol, tween 61, cacao butter, laurin, glycerogelatin and the like.
본 발명에서 사용되는 용어 "투여"는 임의의 적절한 방법으로 개체에게 소정의 본 발명의 조성물을 제공하는 것을 의미한다.The term "administering" as used herein is meant to provide any desired composition of the invention to a subject in any suitable manner.
본 발명은 약학 조성물은 연구자, 수의사, 의사 또는 기타 임상에 의해 생각되는 조직계, 동물 또는 인간에서 생물학적 또는 의학적 반응을 유도하는 유효 성분 또는 약학적 조성물의 양, 즉 치료되는 질환 또는 장애의 증상의 완화를 유도하는 양인 치료상 유효량으로 투여할 수 있다. 본 발명의 약학 조성물에 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, 투여시간, 투여 경로 및 조성물의 분비율, 치료기간, 동시 사용되는 약물을 비롯한 다양한 인자에 따라 조절될 수 있다. 바람직한 효과를 위해서, 본 발명의 약학 조성물은 1~10,000㎎/㎏/day, 바람직하게는 1~200㎎/㎏/day의 양으로 투여할 수 있으며, 하루에 한번 투여할 수도 있고, 수 회에 나누어 투여할 수도 있다. The present invention relates to pharmaceutical compositions comprising 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, physician or other clinician, RTI ID = 0.0 > effective < / RTI > amount. It will be apparent to those skilled in the art that the therapeutically effective dose and frequency of administration for the pharmaceutical compositions of the present invention will vary with 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. For a desired effect, the pharmaceutical composition of the present invention may be administered in an amount of 1 to 10,000 mg / kg / day, preferably 1 to 200 mg / kg / day, or may be administered once a day, It may be administered separately.
본 발명의 약학 조성물은 개체에게 다양한 경로로 투여될 수 있다. 투여의 모든 방식은 예상될 수 있는데, 예를 들면, 경구, 직장 또는 정맥, 근육, 피하, 자궁 내 경막 또는 뇌혈관 내 주사에 의해 투여될 수 있다. The pharmaceutical compositions of the present invention can be administered to a subject in a variety of routes. All modes of administration may be expected, for example, by oral, rectal or intravenous, intramuscular, subcutaneous, intra-uterine dural or intracerebral injection.
또한 본 발명의 조성물은 비만, 비만 관련 질환 또는 합병증의 예방 또는 치료를 위하여 단독으로, 또는 수술, 방사선 치료, 호르몬 치료, 화학 치료 또는 생물학적 반응 조절제를 사용하는 방법들과 병용하여 사용할 수 있다.In addition, the composition of the present invention can be used alone or in combination with methods using surgery, radiation therapy, hormone therapy, chemotherapy or biological response modifiers for the prevention or treatment of obesity, obesity-related diseases or complications.
또한 본 발명은 감국 추출물 또는 분획물을 유효성분으로 포함하는 비만, 비만 관련 질환 또는 합병증의 예방 또는 개선용 식품 조성물을 제공한다. 본 발명의 감국 추출물 또는 분획물이 식품 첨가물로 사용할 경우, 상기 감국 추출물 또는 분획물을 그대로 첨가하거나, 다른 식품 또는 식품 성분과 함께 혼합하여 사용되는 등 통상적인 방법에 따라 적절하게 사용될 수 있다. The present invention also provides a food composition for preventing or ameliorating obesity, obesity-related diseases or complications, which comprises extracts or fractions of Ganoderma lucidum as an active ingredient. When the cuttlefish extract or fraction of the present invention is used as a food additive, the cuttlefish extract or fraction may be added as it is, mixed with other food or food ingredients, and used appropriately according to a conventional method.
또한 상기 유효성분인 감국 추출물 또는 분획물의 혼합양은 사용 목적(예방, 건강 또는 치료적 처치)에 따라 적합하게 변경될 수 있음은 물론이며, 상기 감국 추출물 또는 분획물은 식품 조성물 총 중량에 대하여 0.01~95중량%로 포함되는 것이 바람직하며, 더욱 바람직하게는 1~80중량%로 포함되는 것이다. 그 함량이 0.01중량% 미만일 경우에는 복용 효율성이 떨어질 수 있으며, 95중량%를 초과할 경우에는 제형화의 어려움이 있을 수 있다.In addition, the mixed amount of the extract or fraction of the extract of the present invention may be suitably changed according to the purpose of use (prevention, health or therapeutic treatment), and the extract or fraction of the extract is preferably 0.01 to 95% By weight, and more preferably from 1 to 80% by weight. If the content is less than 0.01% by weight, the efficiency of taking may be lowered. If the content is more than 95% by weight, formulation may be difficult.
구체적인 예로, 식품 또는 음료의 제조 시에는 본 발명의 감국 추출물 또는 분획물은 원료에 대하여 15중량% 이하, 바람직하게는 10중량% 이하의 양으로 첨가되는 것이다. 그러나 건강 및 위생을 목적으로 하거나 또는 건강 조절을 목적으로 하여 장기간 섭취할 경우에는 상기 범위 이하의 양으로 첨가될 수 있으며, 안전성 면에서 아무런 문제가 없기 때문에 유효성분은 상기 범위 이상의 양으로도 사용될 수 있다. As a specific example, at the time of manufacturing a food or beverage, the cuttlefish extract or fraction of the present invention is added in an amount of 15% by weight or less, preferably 10% by weight or less, based on the raw material. However, when it is intended for health and hygiene purposes or for the purpose of controlling health, it can be added in an amount below the above range, and there is no problem in terms of safety. Therefore, the active ingredient can be used in an amount exceeding the above range have.
상기 식품의 종류에는 특별한 제한은 없다. 본 발명의 감국 추출물 또는 분획물을 첨가할 수 있는 식품의 예로는 육류, 소시지, 빵, 초콜릿, 캔디류, 스낵류, 과자류, 피자, 라면, 기타 면류, 껌류, 아이스크림류를 포함한 낙농제품, 각종 수프, 음료수, 차, 드링크제, 알코올 음료, 비타민 복합제 등이 있으며, 통상적인 의미에서의 건강식품을 모두 포함한다.There is no particular limitation on the kind of the food. Examples of the food to which the hamster extract or fraction of the present invention can be added include meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gums, dairy products including ice cream, various soups, , Tea, a drink, an alcoholic beverage, a vitamin complex, and the like.
본 발명의 식품 조성물이 음료로 제조될 경우 통상의 음료와 같이 여러 가지 향미제 또는 천연 탄수화물 등의 추가 성분을 포함할 수 있다. 상기 천연 탄수화물로는 포도당, 과당 등의 모노사카라이드; 말토오스, 수크로오스 등의 디사카라이드; 덱스트린, 사이클로덱스트린 등의 천연 감미제나 사카린, 아스파르탐 등의 합성 감미제 등이 사용될 수 있다. 상기 천연 탄수화물은 본 발명의 식품 조성물 총 중량에 대하여 0.01~10중량%, 바람직하게는 0.01~0.1중량%로 포함되는 것이다.When the food composition of the present invention is prepared as a beverage, it may contain additional ingredients such as various flavors or natural carbohydrates such as ordinary beverages. Examples of the natural carbohydrate include monosaccharides such as glucose and fructose; Disaccharides such as maltose and sucrose; Natural sweeteners such as dextrin and cyclodextrin, synthetic sweeteners such as saccharin and aspartame, and the like. The natural carbohydrate is contained in an amount of 0.01 to 10% by weight, preferably 0.01 to 0.1% by weight based on the total weight of the food composition of the present invention.
상기 외에 본 발명의 식품 조성물은 여러 가지 영양제, 비타민, 전해질, 풍미제, 착색제, 펙트산 및 그의 염, 알긴산 및 그의 염, 유기산, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알코올, 탄산음료에 사용되는 탄산화제 등을 포함할 수 있다. 뿐만 아니라, 본 발명의 조성물은 천연 과일주스, 과일주스 음료 및 야채 음료의 제조를 위한 과육을 포함할 수 있다. 이러한 성분은 독립적으로 또는 조합하여 사용할 수 있다. 상기의 첨가제 비율은 크게 제한되지는 않으나, 본 발명의 식품 조성물 총 중량에 대하여 0.01~0.1중량% 범위내로 포함되는 것이 좋다. In addition to the above, the food composition of the present invention may contain various nutrients, vitamins, electrolytes, flavors, colorants, pectic acid and salts thereof, alginic acid and its salts, organic acids, protective colloid thickeners, pH adjusters, stabilizers, preservatives, glycerin, , Carbonating agents used in carbonated beverages, and the like. In addition, the compositions of the present invention may include flesh for the production of natural fruit juices, fruit juice drinks and vegetable drinks. These components may be used independently or in combination. The proportion of the above additives is not limited to a great extent, but may be in the range of 0.01 to 0.1% by weight based on the total weight of the food composition of the present invention.
이하에서는 실시예를 들어 본 발명에 관하여 더욱 상세하게 설명할 것이나. 이들 실시예는 단지 설명의 목적을 위한 것으로 본 발명의 보호 범위를 제한하고자 하는 것은 아니다.Hereinafter, the present invention will be described in more detail with reference to examples. These embodiments are for purposes of illustration only and are not intended to limit the scope of protection of the present invention.
실시예Example 1. One. 감국Exclusion 추출물 제조 Extract preparation
공기중에서 건조한 감국(Chrysanthemum indicum flowers. CI) 식물체 3.0㎏을 환류추출장치를 이용하여 70% 에탄올로 3회 반복 추출하여 감국 추출물 500g(수율 16.67%)을 얻었다. 3.0 ㎏ of Chrysanthemum indicum flowers (CI), which was dried in the air, was extracted three times with 70% ethanol using a reflux extracting machine to obtain 500 g (yield: 16.67%) of Chum koji extract.
실시예Example 2. 2. 감국Exclusion 분획물Fraction 제조 Produce
상기 실시예 1에서 얻은 감국 추출물 500g을 물에 녹인 다음, 디클로로메탄(dichloromethan, CH2Cl2)층을 분리하는 과정을 3회 반복하였다. 이렇게 얻어진 디클로로메탄 층을 합하여 감압 농축하여 분말형태의 감국 디클로로메탄 분획물 200g(수율 40%)을 얻었다. 남은 물층에 에틸아세테이트(ethyl acetate, CH3COOC2H5)를 가하여 위와 동일한 방법으로 분획하였으며, 감압 농축 후 동결건조하여 분말형태의 감국 에틸아세테이트 분획물 110g(수율 22%)과 물 분획물 190g(수율 38%)을 얻었다.500 g of the mugwort extract obtained in Example 1 was dissolved in water and then the dichloromethane (CH 2 Cl 2 ) layer was separated three times. The dichloromethane layers thus obtained were combined and concentrated under reduced pressure to obtain 200 g (yield: 40%) of a powdery tungstoc dichloromethane fraction. To the remaining water layer was added ethyl acetate (CH 3 COOC 2 H 5 ) and fractionation was carried out in the same manner as above. The filtrate was concentrated under reduced pressure and lyophilized to obtain 110 g (yield: 22%) of powdery gum tragacanth ethyl acetate fraction and 190 g 38%).
실시예Example 3. 7종의 단일 3. Seven single species 분획물Fraction 분리 detach
도 1에 도시한 바와 같이 상기 실시예 2에서 얻어진 에틸아세테이트 분획물과 물 분획물에서 총 32개의 감국 분획 단일 분획물을 얻었고, 그 중 비만에 효과가 있는 것으로 사료되는 7종의 단일 분획물을 분리하였다.As shown in FIG. 1, a total of thirty-two shrimp fractions were obtained from the ethyl acetate fraction and the water fraction obtained in Example 2, and seven single fractions, which were considered to be effective for obesity, were isolated.
에틸아세테이트 분획물을 이용하여 다음과 같이 3종의 단일 분획물을 분리하였다.The ethyl acetate fractions were used to separate the three single fractions as follows.
먼저, 퀘세틴을 분리하기 위하여 실리카 겔 상에서 에틸아세테이트 분획을 컬럼을 이용하여 디클로로메탄과 메탄올 혼합용매를 사용하여 용해 분리하고, 분획은 TLC로 조정하였으며, 메탄올 용매를 증가시키면서 8개의 분획을 얻었다. 그 후, C.4번 분획에서 실리카겔 컬럼을 이용하여 메탄올과 물 혼합용매를 사용하여 퀘세틴(quercetin), 메틸 3,5-디-O-카페오일 퀴네이트(methyl 3,5-di-O-caffeoyl quinate)를 분리하였다.First, in order to separate quercetin, ethyl acetate fraction on silica gel was separated by using a column in a mixed solvent of dichloromethane and methanol. The fraction was adjusted by TLC, and eight fractions were obtained while increasing methanol solvent. Thereafter, a silica gel column was used in fraction C.4 to prepare quercetin, methyl 3,5-di-O-caffeoyl quinate (methyl 3,5-di-O -caffeoyl quinate).
그 후, C.5번 분획에서 실리카겔 컬럼을 이용하여 상기와 동일한 분획 과정을 거쳐 1,3-디카베오일퀴닌산(1,3-dicaffeoylquinic acid), 트리신(tricin), 이소람네틴 3-O-β-D-글루코피라노사이드(isorhamnetin-3-O-β-D-glucopyranoside) 및 아피게닌-7-O-β-D-글루코피라노사이드(apigenin-7-O-β-D-glucoppyranoside)을 분리하였다. Thereafter, fraction C.5 was subjected to the same fractionation process as above using a silica gel column to obtain 1,3-dicaffeoylquinic acid, tricin, isorhamnetin 3- O-beta-D-glucopyranoside and apigenin-7-O-beta-D-glucopyranoside. glucopyranoside.
그 후, C.7번 분획에서 실리카겔 컬럼을 이용하여 상기와 동일한 분획 과정을 거쳐 메틸 3,4-di-O-카페오일 퀴네이트(methyl 3,4-di-O-caffeoyl-quinate), 루테오린-7-O-β-D-글루코피라노사이드(luteorin-7-O-β-D-glucopyranoside), 아세틴-7-O-β-D-글루코피라노사이드(acetin-7-O-β-D-glucopyranoside) 및 리나린(Linarin)을 분리하였다.Thereafter, the same fractionation procedure as above was carried out using a silica gel column in C.7 fraction to obtain methyl 3,4-di-O-caffeoyl-quinate, 7-O-beta-D-glucopyranoside, acetin-7-O-beta-D-glucopyranoside, -β-D-glucopyranoside) and linarin.
그 다음, 물 분획물을 이용하여 다음과 같이 4종의 단일 분획물을 분리하였다.The water fractions were then used to separate the four single fractions as follows.
물 분획물을 컬럼을 이용하여 메탄올과 물 혼합용매를 사용하여 용해 분리 하였고, 분획은 TLC로 조정하였으며, 메탄올 용매를 증가하면서 3개의 분획을 얻었다.The water fractions were dissolved and separated by using methanol and water mixtures using a column. The fractions were adjusted by TLC and three fractions were obtained while increasing methanol solvent.
그 후, D.1번 분획에서 실리카겔 컬럼을 이용하여 클로로포름과 메탄올 혼합용매를 사용하여 클로로제닌산(chlorogenic aicd), 티미딘(THymidine), 디하이드로시린진(dihydrosyringin) 및 아데노산(adenosine)을 분리하였다.Thereafter, a mixture of chloroformic acid, chloramphenic acid, thymidine, dihydrosyringin and adenosine was obtained by using a silica gel column in fraction D.1 and using a mixed solvent of chloroform and methanol. Respectively.
그 후, D.2번 분획에서 실리카겔 컬럼을 이용하여 클로로포름과 메탄올 혼합용매를 사용하여 β-페닐에토시-β-D-글루코피라노사이드(β-phenylethoxy-β-D-glucopyranoside), 벤질-β-D-글루코피라노사이드(benzyl-β-D-glucopyranoside), 크립토클로로제닌산 메틸 에스터(cryptochlorogenic aicd methyl ester) 및 클로로제닌산 메틸 에스터(chlorogenic aicd methyl ester)를 분리하였다.Thereafter, a mixture of chloroform and methanol was used in a fraction of D.2 using a silica gel column to obtain β-phenylethoxy-β-D-glucopyranoside, benzyl- benzyl-β-D-glucopyranoside, cryptochlorogenic aicd methyl ester and chlorogenic aicd methyl ester were separated.
실험예Experimental Example 1. 세포 생존력 측정 1. Measurement of cell viability
1-1. 3T3-L1 1-1. 3T3-L1 지방전구세포의Adipose precursor cell 준비 및 배양 Preparation and Culture
지방전구세포와 지방세포의 증식 억제능을 확인하기 위해, 3T3-L1 지방전구세포를 American Type Culture Collection(ATCC, USA)으로부터 분양받아 사용하였다. 3T3-L1 세포는 지방 세포의 대사 과정 연구에 널리 이용되는 세포주로서, 상기 세포의 분화가 활발히 일어날수록 지방 세포 내의 지방 축적도 활발히 일어난다. 미국 세포주은행(ATCC)에서 받은 세포주는 10% 송아지 혈청(Bovine Calf Serum ; BCS), 1% 페니실린이 함유된 DMEM 배지로 5% CO2와 37℃가 유지되는 배양기 내에서 배양하였다. 2회 이상의 계대배양을 거쳐 세포가 안정화되었을 때 실험에 사용하였다.3T3-L1 adipose precursor cells were purchased from the American Type Culture Collection (ATCC, USA) in order to confirm the proliferative ability of lipid precursor cells and adipocytes. 3T3-L1 cells are widely used for the study of the metabolic process of adipocytes. As the differentiation of these cells occurs actively, the accumulation of fat in the adipocytes is also actively induced. Cell lines from the American Cell Line Bank (ATCC) were cultured in DMEM medium supplemented with 10% Bovine Calf Serum (BCS) and 1% penicillin in an incubator maintained at 37 ° C with 5% CO 2 . When the cells were stabilized through two or more subcultures, they were used for the experiment.
1-2. 세포 생존력 측정1-2. Cell viability measurement
상기 실시예 1 내지 3에서 얻어진 감국 추출물, 분획물 및 7종의 단일 분획물의 세포생존력을 분석하기 위하여 MTT(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) 에쎄이를 사용하여 실험을 수행하였다. 상기 농도로 접종하고, 24시간 동안 배양기에 배양한 후, 배양배지를 바꿔준 후 독성이 없는 감국 추출물 및 분획물의 적정 농도를 찾기 위해 감국 추출물 및 분획물은 4, 20, 100㎍/㎖ 농도로 처리하고, 7종의 단일 분획물은 0.4, 2, 10uM으로 처리하여 37℃, 5% CO2에서 24시간 동안 인큐베이션 하였다. 이후 MTT 완충액을 사용하여 측정하였다. 이 실험 과정은 기준시료 및 샘플을 세 세트로 실험하였다. 세포생존율을 하기 수학식 1로 계산하였으며, 그 결과를 도 2에 나타내었다.To evaluate the cell viability of the hamster extract, fractions and seven single fractions obtained in Examples 1 to 3, MTT (3- (4,5-dimethylthiazol-2-yl) -2,5-diphenyl tetrazolium bromide) Were used. After culturing in the incubator for 24 hours, the culture broth was changed, and then the extracts and fractions were subjected to treatment at a concentration of 4, 20 and 100 μg / ml in order to find an appropriate concentration of the extracts and fractions without toxicity And 7 single fractions were treated with 0.4, 2, 10 uM and incubated at 37 ° C and 5% CO 2 for 24 hours. And then measured using MTT buffer. This experimental procedure was conducted with three sets of reference samples and samples. The cell viability was calculated by the following
[수학식 1][Equation 1]
세포 생존율(%) = (시료처리군의 흡광도 / 대조군의 흡광도) x 100Cell survival rate (%) = (absorbance of sample treated group / absorbance of control group) x 100
실험결과 도 2에 나타낸 바와 같이, 본 발명의 유효성분인 감국 추출물, 에틸아세테이트 분획물 및 물 분획물은 고농도에서 독성이 없음을 확인하였다. 또한 단일성분도 고농도에서 독성이 없음을 확인하였다.2. Experimental Results As shown in Fig. 2, it was confirmed that the extract of T. gomi, the ethyl acetate fraction and the water fraction, which are effective ingredients of the present invention, are not toxic at a high concentration. In addition, it was confirmed that single component was not toxic at high concentration.
실험예Experimental Example 2. 지방 세포로의 분화 억제 확인 2. Identification of inhibition of differentiation into adipocytes
2-1. 지방세포 분화 확인2-1. Identification of adipocyte differentiation
안정화된 3T3-L1 지방전구세포는 2×105cell/well의 밀도로 48well plate에 분주하고 배양하여 100% confluent 시점이 되면 2일 동안 더 유지시켰다. 지방전구세포는 MDI(0.5mM 3-이소부틸-1-메틸잔틴(IBMX), 1μM 덱타메타손, 1μg/mL 인슐린)를 포함하는 10% 소태아혈청(Fetal Bovine Serum, FBS), 1% 페니실린을 함유하는 DMEM 배지로 지방세포 분화를 2일 동안 유도하였고, 배양 48시간 후 1μg/mL 인슐린이 포함된 10% FBS, 1% 페니실린 함유 DMEM 배지로 2일 동안 배양하였다. 그 후, 6일 동안 2일마다 10% FBS, 1% 페니실린 함유 배지를 교체하여 배양하였다. 지방세포 분화 과정 동안 감국 추출물, 에틸아세테이트 분획물 및 물 분획물을 각 배양액에 각각 4, 20, 100㎍/㎖의 농도로 처리하였고, 7종이 단일 분획물은 0.4, 2, 10uM의 농도로 처리하였으며, 분화가 완성되는 시점인 10일째 지방세포 분화 정도를 관찰하였다.Stabilized 3T3-L1 adipose precursor cells were cultured in a 48-well plate at a density of 2 × 10 5 cells / well and maintained at 100% confluent for 2 days. Preadipocytes were cultured in RPMI 1640 supplemented with 10% Fetal Bovine Serum (FBS), 1% penicillin (Sigma) supplemented with MDI (0.5 mM 3-isobutyl-1-methylxanthine (IBMX), 1 μM dexamethasone, For 2 days. After 48 hours of incubation, the cells were cultured for 2 days in DMEM containing 10% FBS and 1% penicillin containing 1 μg / mL insulin. Then, the culture medium containing 10% FBS and 1% penicillin was replaced every two days for 6 days. During the adipocyte differentiation process, hamsters extract, ethyl acetate fraction and water fraction were treated at 4, 20 and 100 μg / ㎖ in each culture, and 7 kinds of single fraction were treated at 0.4, 2 and 10 uM concentration, And the degree of adipocyte differentiation was observed on the 10th day, which is the completion point.
2-2. Oil Red O 염색2-2. Oil Red O dyeing
감국 추출물, 분획물 및 7종의 단일 분획물의 3T3-L1 지방전구세포의 지방세포로의 분화 억제를 확인하기 위하여 지방적(Lipid droplet)에 특이적으로 반응하는 Oil Red O 염색을 진행하였다.In order to confirm the inhibition of differentiation of 3T3-L1 adipocyte precursor cells from adventitious extract, fraction and 7 kinds of single fraction into adipocytes, Oil Red O staining, which is specific to lipid droplet, was performed.
구체적으로, 상기 2-1과 같이 지방세포 분화를 유도한 세포에서 배지를 제거하고 10% 포르말린(formalin)을 1시간 동안 상온에서 처리하여 고정하였다. 이후 60% 이소프로판올로 세척하고, 각 well을 완전히 건조시켰다. Oil Red O 염색약(60% Oil Red O stock, 40% 멸균증류수)을 1시간 동안 처리한 뒤, 60% 이소프로판올로 2회, 멸균증류수 1회 세척하였다. 결합한 Oil Red O의 용출을 위해 100% 이소프로판올로 10분간 처리하였고, 그 용출액을 520㎚에서 흡광도를 측정하였다. Specifically, the medium was removed from the cells inducing adipocyte differentiation as described in 2-1, and 10% formalin was fixed by treatment at room temperature for 1 hour. Then washed with 60% isopropanol and each well was thoroughly dried. Oil Red O dye (60% Oil Red O stock, 40% sterilized distilled water) was treated for 1 hour and washed twice with 60% isopropanol and once with sterile distilled water. For the elution of the combined Oil Red O, it was treated with 100% isopropanol for 10 minutes, and the absorbance of the eluate was measured at 520 nm.
지방 세포에서의 지방 축적율을 하기 수학식 2로 계산하였으며, 그 결과를 도 3에 나타내었다. The fat accumulation rate in adipocytes was calculated by the following equation (2), and the results are shown in FIG.
[수학식 2]&Quot; (2) "
지방 축적율 (%) = (시료처리군의 흡광도 / 대조군의 흡광도) x 100Fat accumulation rate (%) = (absorbance of sample treated group / absorbance of control group) x 100
도 3에 나타낸 바와 같이, 본 발명의 유효성분인 감국 추출물, 에틸아세테이트 분획물 및 물 분획물 처리에 의해 지방 세포내 지방 축적이 농도 의존적으로 억제된 것을 확인하였으며, 단일 성분 처리에 의해 지방세포 내 지방 축적이 농도 의존적으로 억제됨을 확인하였다. As shown in FIG. 3, it was confirmed that fat accumulation in adipocytes was inhibited in a concentration-dependent manner by the treatment with the extract of Tami, ethyl acetate fraction and water fraction, which are effective ingredients of the present invention. Was inhibited in a concentration-dependent manner.
따라서, 본 발명의 본 발명의 감국 추출물 및 감국 분획물, 특히 7종 단일 분획물이 지방전구세포의 지방세포로의 분화를 효율적으로 억제하여 비만의 예방 또는 치료 효과가 우수함을 알 수 있었다.Therefore, it has been found that the extract of the present invention and the gangue fractions of the present invention of the present invention efficiently inhibit the differentiation of adipose precursor cells into adipocytes and thereby prevent or treat obesity.
실험예Experimental Example 3. 3. C57BLC57BL /6 마우스에서의 / 6 in mouse 항비만Anti-obesity 활성 activation
3-1. 실험모델 구축3-1. Build an experimental model
비만의 실험적 모델을 구축하기 위하여 C57BL/6J 웅성 마우스(20~25g)로 5주령을 샘타코(오산, 한국)에서 구입하여 1주 동안 고형사료와 물을 자유롭게 섭취시키면서 일정한 습도(50±10%)와 일정한 온도(22±2℃)및 12시간 주기로 명암이 조절되는 실험 환경에 1주간 적응시켰다. 1주일 동안 적응 기간을 거친 후, 12군으로 나눈 후 정상대조군(Normal), 비만 유발군(45% HFD), 감국 추출물 처리군(8, 40, 200㎎/㎏, CIEE+HFD), 감국 에틸아세테이트 분획물 처리군(2, 10, 50㎎/㎏, CIEA+HFD) 및 양성대조군으로 가르시니아 캄보지아 추출물(200㎎/㎏, GC+HFD)군으로 나누었다. 감국 추출물, 감국 분획물 및 가르시니아 캄보지아 추출물은 0.9% 식염수로 용해시킨 후, 45% 고지방 식이 섭취와 동시에 하루에 한번씩 경구투여를 6주간 실시하였으며, 정상대조군과 비만 유발군은 0.9% 살린을 경구투여하였다. 비만 유발군, 감국 추출물 처리군, 감국 에틸아세테이트 분획물 처리군 및 양성대조군은 45% 고지방 식이를 6주일간 자유롭게 섭취하도록 하였으며, 정상대조군은 일반 식이를 자유롭게 섭취하였다. To establish an experimental model of obesity, 5-week-old male C57BL / 6J mice (20 ~ 25g) were purchased from Sam Taco (Osan, Korea) ), A constant temperature (22 ± 2 ℃) and a 12-hour cycle. After the adaptation period for one week, the animals were divided into 12 groups. Normal control group, obese group (45% HFD), hamster extract group (8, 40, 200mg / kg, CIEE + HFD) (200 mg / kg, GC + HFD) as a positive control group, and treated with acetate fraction (2, 10, 50 mg / kg, CIEA + HFD) The extracts from the mungbean extracts, the mungbean fractions and the Garcinia cambogia extract were dissolved in 0.9% saline, and then oral administration was conducted for 6 weeks at a time of the 45% high fat diet intake. Oral administration of 0.9% saline was carried out in the normal control group and the obese group . Obesity - induced group, achene extract - treated group, acetic acid fraction - treated group and positive control group were fed a 45% high fat diet for 6 weeks freely.
3-2. 체중 및 3-2. Weight and 식이섭취량의Dietary intake 변화 change
본 발명의 감국 추출물 및 분획물의 항비만 효과를 확인하기 위하여, 체중 및 식이섭취량은 시험 개시일과 개시 후 주 1회 간격으로 측정하여 그 결과를 하기 표 1 및 표 2에 나타내었다.In order to confirm the anti-obesity effect of the extract and fractions of the present invention, the body weight and the dietary intake were measured at intervals of one week after the start of the test and at the start thereof, and the results are shown in Tables 1 and 2 below.
상기 표 1 및 표 2에 나타내내 바와 같이, 정상식이군에 비해 고지방 식이군이 유의적으로 체중이 증가하였으며, 이에 반해 가르시니아 캄보지아 추출물군은 고지방식이군에 비해 체중이 50.73% 감소하였다. As shown in Tables 1 and 2, the body weight of the high fat diet group was significantly increased compared to the fat diet group, whereas the weight of the Garcinia cambogia extract group was reduced by 50.73% compared with that of the high fat diet group.
표 1에 나타난 바와 같이 감국 추출물 처리군은 고지방 식이군에 비해 체중이 각각 22.28, 34.77 및 43.44% 감소하였고, 표 2에 나타난 바와 같이 감국 에틸아세테이트 분획물 처리군은 고지방 식이군에 비해 체중이 각각 37.34, 39.21 및 64.05% 감소함을 확인할 수 있었다.As shown in Table 1, the body weight of the mugwort extract-treated group was 22.28, 34.77 and 43.44% lower than that of the high fat dietary group, and the body weight of the mugwort ethyl acetate fraction treated group was 37.34 , 39.21 and 64.05%, respectively.
따라서, 본 발명의 유효성분인 감국 추출물 및 분획물은 실험동물의 체중을 농도의존적으로 유의성 있게 감소시켰으며, 특히 감국 에틸아세테이트 분획물 50㎎/㎏에서 대조군인 가르시니아 캄보지아 군보다 체중 감소가 현저히 크게 나타났으며, 이러한 결과로부터 본 발명의 유효성분인 감국 추출물 및 분획물은 항비만 효과가 우수함을 알 수 있었다.Therefore, the body weight of the hamster extract and fraction, which is an active ingredient of the present invention, significantly decreased the body weight of the experimental animals in a concentration-dependent manner, and the weight loss was markedly larger than that of the control group, Garcinia cambogia, in the hamangi ethyl acetate
3-3. 장기중량 및 지방조직 무게 측정3-3. Long-term weight and fat tissue weighing
본 발명의 감국 추출물 및 분획물의 항비만 효과를 확인하기 위하여, 상기 3-1에서 준비한 실험 동물의 간 조직, 신장 조직 및 백색 부고환 지방 조직의 무게를 측정하였다. 구체적으로, 상기 3-1에서의 실험기간 종료 후, 실험동물을 에테르 마취하여 희생시킨 후, 복부를 절개하고, 각 조직을 적출하여 생리 식염수를 이용해 혈액 및 이물질을 제거하고 무게를 측정하였다. 그 결과는 하기 표 3 및 표 4에 나타내었다.In order to confirm the anti-obesity effect of the hamster extract and fractions of the present invention, the liver tissues, kidney tissues and white epididymal fat tissues of the experimental animals prepared in the above 3-1 were weighed. Specifically, after the experiment period of the above-mentioned 3-1, the experimental animals were anesthetized with ether and sacrificed. Then, the abdomen was excised and the tissues were extracted, and blood and foreign substances were removed using physiological saline and the weight was measured. The results are shown in Tables 3 and 4 below.
상기 표 3 및 표 4에 나타낸 바와 같이, 백색 부고환 지방의 경우 정상대조군(Normal)에 비해 비만 유발군(HFD)이 유의적으로 무게가 증가한 반면, 가르시니아 캄보지아 추출물군(GC)은 유의적으로 무게가 감소함을 확인할 수 있었다. 또한, 본 발명의 유효성분인 감국 추출물 및 분획물 처리군에서는 백색 부고환 지방 조직의 무게가 농도 의존적으로 유의성있게 감소함을 확인할 수 있었다. As shown in Tables 3 and 4, in the case of white epididymal fat, the obesity-induced group (HFD) significantly increased in weight compared to the normal control group, whereas the group of Garcinia cambogia extract (GC) Was decreased. In addition, it was confirmed that the weight of white epididymal adipose tissue was significantly decreased in the concentration-dependent manner in the group treated with the extract of Gamma-ray and the fraction treated with the active ingredient of the present invention.
따라서, 본 발명의 감국 추출물 및 분획물은 항비만 효과가 우수함을 알 수 있었다.Therefore, it was found that the cuttlefish extract and fraction of the present invention had an excellent anti-obesity effect.
3-4. 혈청 내 중성지방 농도의 측정3-4. Measurement of triglyceride concentration in serum
본 발명의 감국 추출물의 항비만 효과를 확인하기 위하여, 실험 종료 후 실험동물의 혈액 내 중성지방의 농도를 측정하였다.In order to confirm the anti-obesity effect of the extract of the present invention, the concentration of triglyceride in the blood of the experimental animals was measured after the completion of the experiment.
구체적으로, 혈액은 실험이 종결된 후 절식, 마취 후 심장 채혈하였으며, 채취한 혈액은 상온에서 30분간 방치한 후 4℃에서 3000rpm으로 10분간 원심분리하여, 혈청(serum)을 얻어 중성지방(triglyceride), 총 콜레스테롤(total cholesterol), 고밀도 지단백질(high density lipoprotein) 및 저밀도 지단백질(low density lipoprotein) 농도를 아산제약(Asanpharm, Korea) kit를 이용하여 측정하였고, 그 결과를 하기 표 5 및 표 6에 나타태었다. Blood was collected after the experiment was terminated and cardiac blood was drawn after anesthesia. The collected blood was allowed to stand at room temperature for 30 minutes and then centrifuged at 4 ° C for 3 minutes at 3000 rpm for 10 minutes to obtain serum (triglyceride ), Total cholesterol, high density lipoprotein and low density lipoprotein concentrations were measured using Asanpharm (Korea) kit. The results are shown in Tables 5 and 6 Respectively.
상기 표 5 및 표 6에 나타낸 바와 같이, 정상대조군(Normal)에 비해 비만 유발군(HFD)의 혈청 내 중성지방, 총콜레스테롤 및 저밀도 지단백질의 농도가 높게 나타났으며, 고밀도 지단백질은 농도가 낮게 나타남음 확인할 수 있었다. 반면, 본 발명의 유효성분인 감국 추출물 및 분획물 처리군에서는 비만 유발군에 비해 혈청 내 중성지방, 총 콜레스테롤 및 저밀도 지단백질의 농도는 낮게 나타났으며, 고밀도 지단백질 농도는 높게 나타남을 확인할 수 있었다.As shown in Tables 5 and 6, the concentration of triglyceride, total cholesterol, and LDL-cholesterol in the serum of the obesity-inducing group (HFD) was higher than that of the normal control group (Normal), and the concentration of the high-density lipoprotein was low I could confirm the sound. On the other hand, the concentration of triglyceride, total cholesterol and low density lipoprotein in the serum was lower and the concentration of high density lipoprotein was higher than that in the obesity-induced group in the hamster extract and fraction treated group of the present invention.
따라서, 본 발명의 감국 추출물 및 분획물은 실험동물의 중성 지방, 총콜레스테롤 및 저밀도 지단백질의 농도를 농도 의존적으로 유의성 있게 감소시키고, 고밀도 지단백질의 농도를 농도 의존적으로 유의성 있게 증가시켜, 항비만 효과가 우수함을 알 수 있었다. Therefore, the extract and fraction of the present invention reduce the concentration of triglyceride, total cholesterol and LDL-cholesterol significantly in a concentration-dependent manner and increase the concentration of the high-density lipoprotein significantly in a concentration-dependent manner, And it was found.
3-4. 혈청 내 3-4. Serum 렙틴Leptin 및 And 아디포넥틴Adiponectin 농도의 측정 Measurement of concentration
본 발명의 감국 추출물 및 분획물의 항비만 효과를 확인하기 위하여, 실험 종료 후 실험동물의 혈액 내 렙틴 및 아디포넥틴 농도를 측정하였다.The leptin and adiponectin concentrations in the blood of the experimental animals were measured at the end of the experiment in order to confirm the anti-obesity effect of the extract and fractions of the present invention.
상기 3-3에서와 같이 심장 채혈하여 채취한 혈액을 원심분리하여 혈청을 얻고, 렙틴(leptin) 및 아디포넥틴(adiponectin)을 측정하였다. 렙틴 및 아디포넥틴의 농도는 ELISA kit을 이용하여 측정하였고, 그 결과를 도 4 및 도 5에 나타내었다.As in 3-3 above, blood collected by cardiac blood collection was centrifuged to obtain serum, and leptin and adiponectin were measured. The concentrations of leptin and adiponectin were measured using an ELISA kit, and the results are shown in FIGS. 4 and 5.
도 4a에 나타낸 바와 같이, 혈청 내 렙틴의 농도는 정상식이군에 비하여 고지방식이군에서 유의적으로 증가되었고, 대조구인 가르시니아 캄보지아 추출물군은 고지방식이군에 비해 유의적으로 감소하였다. 또한, 본 발명의 유효성분인 감국 추출물 투여군에서는 혈청 내 렙틴의 농도가 고지방식이군에 비해 유의적으로 감소함을 확인할 수 있었다.As shown in FIG. 4A, leptin concentration in the serum was significantly increased in the high-fat diet group compared with that in the normal diet group, and the group of Garminia cambogia extract in the control group was significantly lower than that in the high fat diet group. It was also confirmed that the concentration of leptin in the serum was significantly reduced in the group treated with the extract of Tumor Scallops, the active ingredient of the present invention, as compared with that of the high-fat diet group.
도 4b에 나타낸 바와 같이, 혈청 내 아디포넥틴 농도는 정상식이군에 비하여 고지방식이군에서 유의적으로 감소되었고, 대조구인 가르시니아 캄보지아 추출물군은 고지방식이군에 비해 유의적으로 증가되었다. 또한, 본 발명의 유효성분인 감국 추출물 투여군에서는 혈청 내 아디포넥틴의 농도가 고지방식이군에 비해 유의적으로 증가됨을 확인할 수 있었다.As shown in FIG. 4B, the concentration of adiponectin in the serum was significantly lowered in the high-fat diet group than in the high fat diet group, and the control group, Garminia cambogia extract group, was significantly increased compared to the high fat diet group. In addition, it was confirmed that the concentration of adiponectin in the serum was significantly increased in the group administered with the extract of Tumor Scallops, an active ingredient of the present invention, as compared with that of the high-fat diet group.
또한 도 5a에 나타낸 바와 같이, 혈청 내 렙틴의 농도는 정상식이군에 비하여 고지방식이군에서 유의적으로 증가되었고, 대조구인 가르시니아 캄보지아 추출물군은 고지방식이군에 비해 유의적으로 감소하였다. 또한, 본 발명의 유효성분인 감국 추출물 투여군에서는 혈청 내 렙틴의 농도가 고지방식이군에 비해 유의적으로 감소함을 확인할 수 있었다.As shown in FIG. 5A, leptin concentration in the serum was significantly increased in the high fat diet group compared with the fat fat diet group, and the control group, Garminia cambogia extract group, was significantly lower than the high fat diet group. It was also confirmed that the concentration of leptin in the serum was significantly reduced in the group treated with the extract of Tumor Scallops, the active ingredient of the present invention, as compared with that of the high-fat diet group.
도 5b에 나타낸 바와 같이, 혈청 내 아디포넥틴 농도는 정상식이군에 비하여 고지방식이군에서 유의적으로 감소되었고, 대조구인 가르시니아 캄보지아 추출물군은 고지방식이군에 비해 유의적으로 증가되었다. 또한, 본 발명의 유효성분인 감국 추출물 투여군에서는 혈청 내 아디포넥틴의 농도가 고지방식이군에 비해 유의적으로 증가됨을 확인할 수 있었다.As shown in FIG. 5B, the concentration of adiponectin in the serum was significantly lower in the high-fat diet group than in the high fat diet group, and that in the control group, Garminia cambogia, was significantly higher than that in the high fat diet group. In addition, it was confirmed that the concentration of adiponectin in the serum was significantly increased in the group administered with the extract of Tumor Scallops, an active ingredient of the present invention, as compared with that of the high-fat diet group.
이같은 결과로부터, 본 발명의 항비만 효과가 우수함을 알 수 있었다.From these results, it can be seen that the anti-obesity effect of the present invention is excellent.
실험예Experimental Example 4. 4. 웨스턴Western 블롯Blot
본 발명의 유효성분인 감국 추출물 및 분획물이 비만 관련 유전자를 억제하는지 확인하고자 웨스턴 블롯을 이용하여 PPAR-gamma, C/EBP alpha, C/EBP beta 및 C/EBP delta를 확인하였다.C-EBP alpha, C / EBP beta, and C / EBP delta were confirmed by western blotting in order to confirm that the extracts and fractions of Mamooki extracts of the present invention inhibited obesity-related genes.
먼저, 간 조직 및 백색 부고환 지방 조직에 용해 완충액을 넣어 균질화한 후, 원심분리기를 이용하여 상층액을 얻었다. 이를 12% SDS-폴리아크릴 아미드겔에 로딩한 후 막에 블롯팅하였다. 막을 0.1% 트윈-20이 첨가된 1M 트리스 완충액(TBS, pH 7.2)으로 세척한 후, 5% 탈지유가 첨가된 TBS-T에서 2시간 동안 고정하였다. TBS-T로 세척한 후 항 PPAR-gamma, C/EBP alpha, C/EBP beta 및 C/EBP delta가 표지된 항체를 5% 탈지유가 첨가된 TBS-T에 1:2500의 비율로 희석하여 첨가하였다. 4℃에서 하룻밤 방치한 후, TBS-T로 세척하고 2차 항체를 1:2,000의 비율로 희석하여 1시간 동안 처리하였다. 이후, 단백질 밴드를 강화된 화학발광(enbanced chemiluminesence, ECL) 시스템을 사용하여 가시화하였다.First, the liver tissue and the white epididymal adipose tissue were homogenized by adding a lysis buffer, and then the supernatant was obtained using a centrifuge. This was loaded on a 12% SDS-polyacrylamide gel and blotted onto the membrane. The membranes were washed with 1 M Tris buffer (TBS, pH 7.2) supplemented with 0.1% Tween-20 and fixed in TBS-T supplemented with 5% skim milk for 2 hours. After washing with TBS-T, antibodies labeled with anti-PPAR-gamma, C / EBP alpha, C / EBP beta and C / EBP delta were diluted 1: 2500 in TBS-T supplemented with 5% Respectively. After overnight incubation at 4 ° C, the cells were washed with TBS-T, and the secondary antibody was diluted at a ratio of 1: 2,000 and treated for 1 hour. The protein bands were then visualized using an enbanced chemiluminescence (ECL) system.
도 6 내지 9에 나타낸 바와 같이, 본 발명에 따른 감국 추출물 및 분획물은 농도의존적으로 간 및 백색 부고환 지방 조직에서 PAR-gamma, C/EBP alpha, C/EBP beta 및 C/EBP delta 단백질 발현을 농도의존적으로 억제함을 확인할 수 있었다. 따라서, 본 발명의 감국 추출물 및 분획물은 비만 인자들의 발현을 억제하여, 비만, 비만 관련 질환 또는 합병증의 예방 또는 치료 효과가 우수할 것임을 예측할 수 있었다.As shown in FIGS. 6 to 9, the extracts and fractions according to the present invention exhibit a concentration-dependent expression of PAR-gamma, C / EBP alpha, C / EBP beta and C / EBP delta protein in liver and white epididymal adipose tissue Dependent inhibition. Therefore, it was predicted that the cuttlefish extract and fractions of the present invention inhibit the expression of obesity factors and that the effect of preventing or treating obesity, obesity-related diseases or complications will be excellent.
제제예Formulation example 1. 약학 제제의 제조 1. Manufacture of pharmaceutical preparations
산제Powder 제조 Produce
감국 추출물 또는 분획물 20㎎, 유당 100㎎ 및 탈트 10㎎을 혼합하고 기밀포에 충진하여 산제를 제조하였다.20 mg of hamsters extract or fractions, 100 mg of lactose and 10 mg of talt were mixed and filled in airtight bags to prepare powders.
정제 제조Tablet manufacture
감국 추출물 또는 분획물 10㎎, 옥수수전분 100㎎, 유당 100㎎ 및 스테아린산 마그네슘 2㎎을 혼합한 후 통상의 정제의 제조방법에 따라서 타정하여 정제를 제조하였다.10 mg of hamsters extract or fraction, 100 mg of corn starch, 100 mg of lactose, and 2 mg of magnesium stearate were mixed and tableted according to a conventional preparation method.
캡슐제Capsule 제조 Produce
통상의 캡슐제 제조방법에 따라 감국 추출물 또는 분획물 10㎎, 결정성 셀룰로오스 3㎎, 락토오스 14.8㎎ 및 마그네슘 스테아레이트 0.2㎎을 혼합하고 젤라틴 캡슐에 충전하여 캡슐제를 제조하였다.In accordance with the usual preparation method of capsule, 10 mg of hamsters extract or fraction, 3 mg of crystalline cellulose, 14.8 mg of lactose and 0.2 mg of magnesium stearate were mixed and filled in gelatin capsules to prepare capsules.
주사제 제조Injection manufacturing
통상의 주사제의 제조방법에 따라 1앰플당(2mL) 감국 추출물 또는 분획물 10㎎, 만니톨 180㎎, 주사용 멸균 증류수 2,974㎎ 및 Na2HPO4· 2H2O 26㎎으로 제조하였다.According to the usual injection preparation method, 10 mg of hamchi extract or fraction per 1 ampoule (2 mL), 180 mg of mannitol, 2,974 mg of sterilized distilled water for injection and 26 mg of Na 2 HPO 4 .2H 2 O were prepared.
액제Liquid 제조 Produce
통상의 액제의 제조방법에 따라 정제수에 감국 추출물 또는 분획물 20㎎, 이성화당 10g 및 만니톨 5g을 가하여 용해시키고 레몬향을 적량 가한 다음 상기의 성분을 혼합하였다. 그 다음 정제수를 더 가하여 전체 100mL로 조절한 후 갈색병에 충진하고 멸균시켜 액제를 제조하였다.In accordance with the usual method for preparing a liquid preparation, 20 mg of gypsum extract or fraction, 10 g of isomerized sugar and 5 g of mannitol were added to purified water and dissolved, and the lemon flavor was added in an appropriate amount. Then, purified water was further added thereto, adjusted to a total volume of 100 mL, filled in a brown bottle, and sterilized to prepare a liquid preparation.
제제예Formulation example 2. 식품 제제의 제조 2. Manufacture of food preparation
건강식품 제조Health food manufacturing
감국 추출물 또는 분획물 100㎎, 비타민 혼합물 적량, 비타민 A 아세테이트 70g, 비타민 E 1.0㎎, 비타민 B1 0.13㎎, 비타민 B2 0.15㎎, 비타민 B6 0.5㎎, 비타민 B12 0.2g, 비타민 C 10㎎, 비오틴 10g, 니코틴산아미드 1.7㎎, 엽산 50g, 판토텐산 칼슘 0.5㎎, 무기질 혼합물 적량, 황산제1철 1.75㎎, 산화아연 0.82㎎, 탄산마그네슘 25.3㎎, 제1인산칼륨 15㎎, 제2인산칼슘 55㎎, 구연산칼륨 90㎎, 탄산칼슘 100㎎ 및 염화마그네슘 24.8㎎을 혼합한 다음, 과립을 제조하고 통상의 방법에 따라 건강식품을 제조하였다. 이때, 상기 비타민 및 미네랄 혼합물의 조성비는 비교적 건강식품에 적합한 성분을 바람직한 실시예로 혼합 조성하였지만, 그 배합비를 임의로 변형 실시하여도 무방하다.100 mg vitamin C acetate, 70 mg vitamin A acetate, 0.13 mg vitamin B, 0.15 mg vitamin B2, 0.5 mg vitamin B6, 0.2 g vitamin B12, 10 mg vitamin C, 10 g biotin, nicotinic acid Amide 1.7 mg, folic acid 50 g, calcium pantothenate 0.5 mg, inorganic mixture suitable amount, ferrous sulfate 1.75 mg, zinc oxide 0.82 mg, magnesium carbonate 25.3 mg, potassium phosphate monohydrate 15 mg, dicalcium phosphate 55 mg, potassium citrate 90 Mg of calcium carbonate, 100 mg of calcium carbonate, and 24.8 mg of magnesium chloride were mixed and granules were prepared and a health food was prepared according to a conventional method. At this time, although the composition ratio of the vitamin and mineral mixture is relatively mixed with the ingredient suitable for health food, it may be arbitrarily modified.
건강음료 제조Health drink manufacturing
통상의 건강음료 제조방법에 따라 감국 추출물 또는 분획물 100㎎, 비타민 C 15g, 비타민 E(분말) 100g, 젖산철 19.75g, 산화아연 3.5g, 니코틴산아미드 3.5g, 비타민 A 0.2g, 비타민 B1 0.25g, 비타민 B2 0.3g 및 정량의 물을 혼합한 다음, 약 1시간 동안 85℃에서 교반 가열한 후 만들어진 용액을 여과하여 멸균된 2L 용기에 취득하여 밀봉 멸균한 뒤 냉장 보관하여 건강음료를 제조하였다. 이때, 상기 조성비는 비교적 기호음료에 적합한 성분을 바람직한 실시예로 혼합 조성하였지만 수요계층이나, 수요국가, 사용용도 등 지역적, 민족적 기호도에 따라서 그 배합비를 임의로 변형 실시하여도 무방하다.According to a conventional method for producing healthy beverages, 100 mg of green tea extract or fraction, 15 g of vitamin C, 100 g of vitamin E (powder), 19.75 g of iron lactate, 3.5 g of zinc oxide, 3.5 g of nicotinic acid amide, 0.2 g of vitamin A, , 0.3 g of vitamin B2 and a predetermined amount of water were mixed and heated at 85 DEG C for about 1 hour with stirring. The resulting solution was filtered to obtain a sterilized 2 L container, sealed sterilized and refrigerated to prepare a health drink. At this time, although the composition ratio of the ingredients suitable for the beverage is comparatively mixed, the mixture ratio may be arbitrarily varied according to the demand, the demanded country, the intended use, and the regional or national preference.
비록 본 발명이 상기에 언급된 바람직한 실시예로서 설명되었으나, 발명의 요지와 범위로부터 벗어남이 없이 다양한 수정이나 변형을 하는 것이 가능하다. 또한 첨부된 청구 범위는 본 발명의 요지에 속하는 이러한 수정이나 변형을 포함한다.Although the present invention has been described in terms of the preferred embodiments mentioned above, it is possible to make various modifications and variations without departing from the spirit and scope of the invention. It is also to be understood that the appended claims are intended to cover such modifications and changes as fall within the scope of the invention.
Claims (7)
상기 분획물은
(a) 감국을 에탄올로 추출하여 감국 에탄올 추출물을 얻는 단계; 및
(b) 상기 감국 에탄올 추출물에 증류수를 가하고 에틸아세테이트를 이용하여 순차적으로 분획하여 에틸아세테이트 분획물을 얻는 단계;로 제조되는 것을 특징으로, 하는 비만의 예방 또는 치료용 약학 조성물.The method according to claim 1,
The fraction
(a) extracting a germ extract with ethanol to obtain a germinated ethanol extract; And
(b) adding distilled water to the germinated ethanol extract, and sequentially fractionating the germinated ethanol extract with ethyl acetate to obtain an ethyl acetate fraction; wherein the pharmaceutical composition is for preventing or treating obesity.
상기 감국 에틸아세테이트 분획물은 퀘세틴(quercetin), 1,3-디카페오일퀴닌산 (1,3-dicaffeoylquinic acid), 메틸 3,4-디-O-카페오일 퀴네이트(mehtyl 3,4-di-O-caffeoyl quinate), 클로로제닌산(chlorogenic acid), 디하이드로시린진(dihydrosyringin) 및 벤질-β-D-글루코피라노사이드(benzyl-β-D-glucopyranoside) 중 선택된 1종 이상을 포함하는 것을 특징으로 하는 비만의 예방 또는 치료용 약학 조성물.The method according to claim 1,
The demineralized ethyl acetate fraction may be selected from quercetin, 1,3-dicaffeoylquinic acid, methyl 3,4-di-O-caffeoyl quinate (mehtyl 3,4-di -O-caffeoyl quinate, chlorogenic acid, dihydrosyringin, and benzyl-β-D-glucopyranoside. Or a pharmaceutically acceptable salt thereof.
상기 감국 에틸아세테이트 분획물은 조성물 총 중량에 대하여 0.01~95중량%로 포함되는 것을 특징으로 하는 비만의 예방 또는 치료용 약학 조성물. The method according to claim 1,
The pharmaceutical composition for the prevention or treatment of obesity according to any one of claims 1 to 3, wherein the demethyl ethyl acetate fraction is 0.01 to 95% by weight based on the total weight of the composition.
상기 감국 에틸아세테이트 분획물은 비만 발현 인자인 PPAR-g 및 C/EBP pathway 단백질 발현량을 감소시키며, 지방전구세포에서 지방세포로의 분화를 억제하며, 혈중 렙틴(leptin)의 발현량을 감소시키며, 아디포넥틴(adiponectin)의 발현량을 증가시키는 것을 특징으로 하는 비만의 예방 또는 치료용 약학 조성물.The method according to claim 1,
The fractions of PPAR-g and C / EBP pathway proteins are reduced, and the expression of leptin in the blood is suppressed by inhibiting the differentiation of adipose precursor cells into adipocytes, adiponectin wherein the expression level of adiponectin is increased.
상기 감국 에틸아세테이트 분획물은 조성물 총 중량에 대하여 0.01~95중량%로 포함되는 것을 특징으로 하는 비만의 예방 또는 개선용 식품 조성물.
The method according to claim 6,
The food composition for prevention or improvement of obesity according to any one of the preceding claims, characterized in that the germacemic ethyl acetate fraction is contained in an amount of 0.01 to 95% by weight based on the total weight of the composition.
Priority Applications (1)
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KR101952644B1 (en) * | 2017-09-21 | 2019-05-23 | 국가식품클러스터지원센터 | The Inhibitory Obesity Effects of Amomum vilosum Loureiro Extracts and Composition Containing the Extract as Effective Ingredient |
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KR102243413B1 (en) * | 2019-01-30 | 2021-04-22 | 주식회사 비티씨 | Method for preparing chrysanthemum indicum extract containing increased content of aglycon by enzymes, and composition for preventing or treating obesity made thereby |
KR102139443B1 (en) * | 2020-03-27 | 2020-07-29 | 연성대학교 산학협력단 | Composition for inhibiting adipogenesis comprising Chrysanthemum indicum fermented by lactic acid bacteria |
KR102642516B1 (en) | 2022-12-28 | 2024-03-05 | (주)에스앤디 | Composition for preventing, improving or treating respiratory diseases comprising mixture of Ecklonia cava extract etc as an active ingredient and method of manufacturing the same |
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KR101952644B1 (en) * | 2017-09-21 | 2019-05-23 | 국가식품클러스터지원센터 | The Inhibitory Obesity Effects of Amomum vilosum Loureiro Extracts and Composition Containing the Extract as Effective Ingredient |
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