KR101078002B1 - Composition comprising galla rhois extract for prevention and treatment of obesity by means of autophagic mechanism - Google Patents
Composition comprising galla rhois extract for prevention and treatment of obesity by means of autophagic mechanism Download PDFInfo
- Publication number
- KR101078002B1 KR101078002B1 KR1020080104394A KR20080104394A KR101078002B1 KR 101078002 B1 KR101078002 B1 KR 101078002B1 KR 1020080104394 A KR1020080104394 A KR 1020080104394A KR 20080104394 A KR20080104394 A KR 20080104394A KR 101078002 B1 KR101078002 B1 KR 101078002B1
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- South Korea
- Prior art keywords
- obesity
- extract
- ethyl acetate
- fraction
- prevention
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- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
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Abstract
본 발명은 오배자 추출물을 함유하는 자가포식을 기전으로 한 비만 예방 및 치료용 조성물에 관한 것으로서, 더욱 상세하게는 오배자 추출물 또는 분획물이 지방세포의 자가포식을 유도하여 지방세포의 증식을 억제하는 활성이 있음을 새롭게 확인함으로써 비만 예방 및 치료용 조성물로서 사용할 수 있는 오배자로부터 유효성분의 분리방법과, 오배자 추출물 또는 분획물을 함유하는 비만 예방 및 치료용 조성물에 관한 것이다. The present invention relates to a composition for the prevention and treatment of obesity based on the autophagy containing the blastocyst extract, and more particularly, the activity of inhibiting the proliferation of fat cells by inducing the autophagy of blastocyte extract or fraction. The present invention relates to a method for separating an active ingredient from a gall which can be used as a composition for preventing and treating obesity, and to a composition for preventing and treating obesity containing a gall extract or fraction.
즉, 본 발명에 따른 오배자 추출물은 세포실험에서는 지방세포의 자가포식을 유도하고, 비만유도 동물모델에서 체중증가를 억제하며, 체중 증가를 유도시킨 동물의 체중을 감소시키는 활성을 나타내며, 혈중 저밀도 지방단백 및 중성지방을 감소시킴으로써 비만 예방, 비만 치료, 비만으로 인한 합병증의 예방에도 유효한 약학 조성물 및 건강식품으로 사용할 수 있다. In other words, the gall extract according to the present invention induces autophagy of adipocytes in cell experiments, inhibits weight gain in obesity-induced animal models, and decreases the weight of animals inducing weight gain. By reducing protein and triglyceride, it can be used as a pharmaceutical composition and health food which is also effective in preventing obesity, treating obesity, and preventing complications due to obesity.
오배자 추출물, 자가포식, 비만 예방, 치료 Gall bladder extract, autophagy, obesity prevention, treatment
Description
본 발명은 오배자 추출물을 함유하는 자가포식을 기전으로 한 비만 예방 및 치료용 조성물에 관한 것이다.The present invention relates to a composition for the prevention and treatment of obesity, based on the autophagy, containing the gall bladder extract.
비만은 인체 내에 약 200억 개 이상 존재하고 있는 지방세포가 에너지의 축적과 방출에 대한 조절의 불균형으로 인하여 과도한 에너지가 축적되어 발생하는 것으로써 지방세포의 수가 증가하고 증가된 지방세포에 에너지와 중성지방이 과도하게 발생되어 지방세포의 크기가 증가하는데 기인하고 있는 것으로 보고되고 있다. 지방세포는 생체 내에서 에너지를 축적하거나 방출하는 역할을 담당하는데 에너지의 수요보다 공급이 많은 경우에 지방세포 내에서 에너지를 중성지방으로 저장하고 에너지가 고갈되었을 때 이를 유리지방산과 글리세롤로 분해하여 에너지원으로 사용한다. 그러나, 이러한 에너지의 과잉공급으로 발생되는 중성지방의 축적이 곧 비만을 야기한다. Obesity is caused by excessive energy accumulation due to the imbalance of energy accumulation and release of fat cells in the body of about 20 billion or more, resulting in an increase in the number of fat cells and an increase in energy and neutrality. It is reported that fat is excessively produced due to an increase in the size of fat cells. Adipose cells accumulate or release energy in the living body. When the supply is greater than the demand for energy, fat cells store energy as triglycerides and decompose it into free fatty acids and glycerol when energy is depleted. Use as a circle. However, the accumulation of triglycerides caused by this oversupply of energy causes obesity.
비만을 치료하기 위하여 종래부터 다양한 노력이 있어왔으며, 지방의 흡수억 제, 포만감을 주어 식욕을 억제함으로써 과잉 에너지의 공급을 막고자하는 노력과 지방분해 촉진, 지방세포 분화 억제, 지방축적 억제를 위하여 생강에서 분리된 쇼가올(shogaol), 카페인(caffenine), 테오필린(theophylline) 등의 물질로 세포의 지방을 분해하거나 아데닐레이트 사이클레이즈(adenylate cyclase)의 촉진, 포스포디에스테라제(phosphodiesterase)의 억제를 통한 지방분해 효능을 나타내는 것들이 보고되어 있다. Various efforts have been made to treat obesity, and efforts to prevent excess energy supply by suppressing appetite by suppressing fat absorption and satiety, promoting lipolysis, inhibiting differentiation of fat cells, and inhibiting fat accumulation. Materials such as shogaol, caffeen, and theophylline, isolated from ginger, break down cell fat, promote adenylate cyclase, and phosphodiesterase There have been reports of lipophilic efficacy through inhibition of.
지방세포 분화 억제 및 지방축적 억제와 관련하여 식물 추출물로부터 지방전구 세포의 분화를 억제함으로써 비만의 예방 및 당뇨병을 예방할 수 있는 식물추출물이 보고되고 있으나, 분화된 지방세포의 지방축적을 억제하고 중성지방이 축적되지 않도록 하는 작용에 대한 규명이 없어 기술적인 한계가 있었다. 한편, 대한민국 특허 제588469호에는 생강으로부터 분리된 쇼가올이 지방세포 분화 및 분화된 지방세포의 지방축적을 억제할 수 있는 기술이 공지되어 있다. 그러나, 상기특허에도 지방세포의 지방축적 억제에 대한 언급은 있으나, 이를 통하여 직접 비만 동물모델에서 비만의 예방 또는 체중증가율 감소와 같은 효과에 대한 언급이 없어 기술적인 한계가 있었다. In relation to the suppression of adipocyte differentiation and the accumulation of fat, plant extracts have been reported to prevent the obesity and prevent diabetes by inhibiting the differentiation of fat precursor cells from plant extracts. There was no technical limitation on the effect of preventing this accumulation. On the other hand, Korean Patent No. 588469 discloses a technique capable of inhibiting adipocyte differentiation and fat accumulation of differentiated adipocytes by shogaol isolated from ginger. However, although there is a reference to the fat accumulation suppression of fat cells in the patent, there was no technical limitation because there is no mention of the effects such as prevention of obesity or reduction of weight gain directly in the obese animal model.
따라서, 천연물을 이용하여 인체에 대하여 안전하고 부작용이 없으며, 지방세포분화 억제, 분화된 지방세포에서의 지방축적을 억제하는 새로운 물질을 개발하고 이에 대한 비만 동물시험모델에서 천연물의 효능을 평가하여 종래의 비만 억제 물질과 동등하거나 그 이상의 효능을 가지는 새로운 물질을 개발할 필요성이 대두되고 있다. Therefore, by developing a new substance that is safe for humans and has no side effects using natural products, and inhibits fat cell differentiation and fat accumulation in differentiated fat cells, and evaluates the efficacy of natural products in an obese animal test model. There is a need to develop a new substance having an efficacy equal to or greater than that of an obesity inhibitor.
자가포식은 새로운 형태의 세포 사멸로서 기존에 알려진 자연사, 괴사 등이 세포 전체의 사멸만을 다루는 것과 달리, 자가포식은 미토콘드리아, 형질세망 등 세포 내 소기관의 사멸 및 재생과 관련이 있다. 세포 내 소기관은 평상시에 정적인 상태를 유지한다고 생각되어 왔으나, 최근의 연구에 의하면 평상시에도 끊임없이 죽고 재생되는 과정을 겪고 있음이 밝혀졌다. 이 과정을 통해 낡고 퇴행성 변화를 겪은 세포 내 소기관은 소멸되어 새로운 세포 내 소기관을 재생하는데 필요한 영양 공급원이 된다. 자가포식은 이러한 세포내 소기관의 사멸 및 재생을 통해 세포 전체를 사멸에서 보호하기도 하고 세포 전체의 사멸을 유도하기도 한다. 그동안 자가포식에 의한 세포 내 소기관의 끊임없는 사멸과 재생의 생리적 기능 및 임상적 의미가 불분명하였으나, 최근 관련 연구가 진행되면서 자가포식과 각종 질병 또는 노화의 관련성이 제시되고 있다. 자가포식이 암, 퇴행성 신경질환 등에 중요한 역할을 한다는 것이 일부 밝혀지기 시작하였으나, 비만과 관련하여 자가포식이 어떠한 역할을 하는지는 알려진 바가 전혀 없다. Autophagy is a new type of cell death, whereas natural death, necrosis, and the like, which deal only with cell death, are associated with the death and regeneration of intracellular organelles such as mitochondria and plasma meshes. Intracellular organelles have been thought to remain static at normal times, but recent studies have shown that they are constantly dying and regenerating in normal times. This process destroys the old, degenerative intracellular organelles, providing a nutrient source for regenerating new intracellular organelles. Autophagy protects the entire cell from killing and induces the death of the whole cell by killing and regenerating these intracellular organelles. The physiological function and clinical significance of the endless killing and regeneration of intracellular organelles by autophagy have been unclear, but recent researches have suggested the relationship between autophagy and various diseases or aging. While it has been shown that autophagy plays an important role in cancer and neurodegenerative diseases, there is no known role of autophagy in relation to obesity.
한편, 오배자는 붉나무(Rhus javanica L.) 또는 그 밖의 동속식물인 옻나무과 (Anacardiaceae)의 잎에 오배자 진딧물(Melaphis chinensis Bell)의 자상에 의하여 생긴 벌레집으로서, 전체의 50~70%가 갈로탄닌류로 갈릭에시드(gallic acid), 펜타갈로일 글루코오즈(pentagalloyl glucose) 등이 주요성분으로 밝혀지고 있다. 본 발명에서는 오배자 추출물이 자가포식을 기전으로 하여 지방세포 분화를 억제하고, 분화된 지방세포의 중성지방 축적을 억제하며, 이로부터 확인된 활성이 비만동물 시험모델에서 복부지방 감소, 간지방 축적 억제, 부고환지방 축적 억제 및 체중 증가 억제를 확인하였으며, 이는 기존에 보고된 바 있는 비만 억제 물질에 비해 동등하거나 그 이상을 효능을 나타내었다. 현재까지 오배자 추출물은 베타세포 손상에 대한 보호작용을 통한 당뇨의 예방 및 치료 효과에 대하여 보고된 바 있으나, 자가포식에 의한 지방세포 분화 억제 및 지방세포의 지방축적 억제를 통한 비만 치료제로서는 보고된 바 없다. On the other hand, the gall bladder is a bug house formed by the stab of the Melaphis chinensis Bell on the leaves of Rhus javanica L. or other similar plant Anacardiaceae. Gallic acid and pentagalloyl glucose have been identified as main ingredients. In the present invention, the gall bladder extract inhibits adipocyte differentiation by inhibiting autophagy, and inhibits the accumulation of triglycerides of differentiated adipocytes. Inhibition of epididymal fat accumulation and weight gain was confirmed, which showed the same or better efficacy than the previously reported obesity inhibitors. To date, five gall extracts have been reported for the prevention and treatment of diabetes through the protective action against beta cell damage, but has been reported as a therapeutic agent for obesity through the inhibition of adipocyte differentiation and the accumulation of fat cells by autophagy. none.
이에, 본 발명자들은 종래 알려진 비만억제제들 보다 효과가 우수하면서 부작용이 없는 생약성분을 찾고자 연구를 거듭한 결과, 오배자(galla rhois) 추출물과 이의 분획물이 자가포식을 기전으로 하여 지방세포의 분화를 억제하고 분화된 지방세포의 지방축적을 억제하며 세포독성이 없어 비만유도 동물모델에서 우수한 비만 억제 효과를 나타냄을 확인함으로써 본 발명을 완성하게 되었다. Therefore, the present inventors conducted a study to find a herbal ingredient that is more effective than conventionally known anti-obesity agents and has no side effects, and the galla rhois extract and its fractions suppress the differentiation of fat cells by the mechanism of autophagy. The present invention was completed by confirming that the fat accumulation of differentiated adipocytes is suppressed and there is no cytotoxicity, and the obesity-inducing animal model exhibits an excellent anti-obesity effect.
따라서, 본 발명은 오배자 추출물 또는 이의 분획물을 유효성분으로 함유하는 비만 예방 및 치료용 조성물을 제공하는데 그 목적이 있다. Therefore, an object of the present invention is to provide a composition for the prevention and treatment of obesity, which contains a fivefold extract or a fraction thereof as an active ingredient.
또한, 본 발명은 오배자 추출물 또는 이의 분획물을 유효성분으로 함유하는 건강식품을 제공하는데 또 다른 목적이 있다.In addition, the present invention is another object to provide a health food containing the gall bladder extract or fractions thereof as an active ingredient.
본 발명은 오배자 추출물 또는 이의 분획물을 유효성분으로 함유하는 비만 예방 및 치료용 조성물을 그 특징으로 한다.The present invention is characterized by the composition for the prevention and treatment of obesity, containing the gall extract or fractions thereof as an active ingredient.
또한, 본 발명은 오배자로부터 유효성분을 분리하는 방법을 또 다른 특징으로 한다.In another aspect, the present invention is characterized by a method for separating the active ingredient from the gall bladder.
또한, 본 발명은 오배자 추출물 또는 이의 분획물을 유효성분으로 함유하는 건강식품을 또 다른 특징으로 한다.In another aspect, the present invention is characterized by a health food containing a fivefold extract or a fraction thereof as an active ingredient.
본 발명은 붉나무(Rhus javanica L.) 또는 그 밖의 동속식물인 옻나무과 (Anacardiaceae)의 잎에 오배자 진딧물(Melaphis chinensis Bell)의 자상에 의하여 생긴 벌레집인 오배자(Galla Rhois) 추출물과 이의 분획물을 유효성분으로 하는 비만 예방 및 치료 조성물에 관한 것으로서, 자가포식에 의하여 전지방세포의 지방세포로의 분화를 억제하고, 분화된 지방세포의 지방축적을 억제함으로써 이를 포함하는 식품 또는 의약 조성물을 통하여 부작용 없이 비만의 치료 및 예방이 가능하다. The present invention is an active ingredient in the extract of Galla Rhois and its fractions, which are insects caused by the stagnation of Melaphis chinensis Bell on the leaves of Rhus javanica L. or other similar plants, Anacardiaceae. The present invention relates to a composition for preventing and treating obesity, the method comprising inhibiting the differentiation of allergic cells into adipocytes by autophagy, and inhibiting fat accumulation of differentiated adipocytes, thereby preventing obesity without side effects through food or pharmaceutical compositions comprising the same. Treatment and prevention are possible.
이와 같은 본 발명을 더욱 상세하게 설명하면 다음과 같다.Hereinafter, the present invention will be described in detail.
본 발명은 오배자(galla rhois) 추출물 또는 유기용매 분획물이 자가탐식에 의하여 전지방세포의 지방세포 분화를 억제하고 분화된 지방세포 내의 지방축적을 억제하며, 비만유도 동물모델에서 체지방을 억제하고, 체중증가를 억제함을 확인하였으며, 혈중 중성지방 및 저밀도지방단백 감소 효능을 확인함으로써, 비만 예방 및 치료용 조성물로서 사용할 수 있는 오배자 추출물에 관한 것이다. In the present invention, galla rhois extract or organic solvent fraction inhibits adipocyte differentiation of all cells by autophagy, inhibits fat accumulation in differentiated adipocytes, inhibits body fat in obesity-induced animal model, It has been confirmed that the increase is suppressed, and by confirming the effect of reducing triglycerides and low-density lipoproteins in the blood, it relates to a gall bladder extract that can be used as a composition for preventing and treating obesity.
먼저, 오배자(Galla Rhois)를 알콜로 추출하여 알콜 추출물을 얻는다. 상 기 알콜은 메탄올, 에탄올, 이소프로판올, 프로판올 및 부탄올 중에서 선택된 1종 이상이 바람직하다.First, Galla Rhois is extracted with alcohol to obtain an alcohol extract. The alcohol is preferably one or more selected from methanol, ethanol, isopropanol, propanol and butanol.
상기 알콜 추출물을 물로 현탁한 후, 노르말 헥산, 디클로로메탄 및 에틸아세테이트로 차례로 분획한 다음 감압 농축하여 분획물을 얻는다.The alcohol extract is suspended with water, and then partitioned with normal hexane, dichloromethane and ethyl acetate in that order, and then concentrated under reduced pressure to obtain a fraction.
상기 에틸아세테이트 분획물을 실리카겔 컬럼 크로마토그래피를 수행하여 활성분획을 수득한다. 이때, 에틸아세테이트와 메탄올의 혼합용매는 98:5 -> 80:20으로 실리카겔 컬럼 크로마토그래피를 수행하여 활성분획물(Rf값 4.5, 헥산과 에틸아세테이트 3:7 용매에서)을 얻는다. 상기 활성분획물 중 TLC 상에서 탄닌산과 동일한 스팟이 검출되는 분획물을 농축하여 MPLC(헥산과 에틸아세테이트 9:1에서 2:8 까지)로 정제하였다.The ethyl acetate fractions are subjected to silica gel column chromatography to obtain an active fraction. At this time, the mixed solvent of ethyl acetate and methanol is subjected to silica gel column chromatography from 98: 5 to 80:20 to obtain an active fraction (R f value 4.5, in hexane and ethyl acetate 3: 7 solvent). Among the active fractions, fractions where the same spot as tannic acid was detected on TLC were concentrated and purified by MPLC (hexane and ethyl acetate 9: 1 to 2: 8).
이렇게 얻어진 정제된 유효성분은 다음 화학식 1로 표시되는 화합물이다.The purified active ingredient thus obtained is a compound represented by the following Chemical Formula 1.
[화학식 1][Formula 1]
상기 화학식 1에서, R1은 
이렇게 얻어진 오배자 알콜 추출물과 분획물이 자가탐식을 통하여 마우스의 전지방세포(3T3-L1)가 지방세포로 분화되는 것을 억제하고, 분화된 지방세포의 지방축적을 억제하며, 상기의 오배자 추출물과 분획물이 동물모델에서 체중감소 효능이 있음을 확인하였다. Thus, gall bladder alcohol extracts and fractions inhibit the differentiation of mouse fat cells (3T3-L1) into adipocytes through autophagy, inhibit the fat accumulation of differentiated adipocytes, It was confirmed that the weight loss efficacy in the animal model.
따라서, 오배자 추출물과 분획물이 함유되어 있는 조성물은 자가 탐식에 의해서 지방세포 분화를 억제하고 지방세포의 지방축적을 억제함으로써 비만 예방 및 치료에 효과적으로 적용될 수 있다. Thus, the composition containing the gall bladder extract and fractions can be effectively applied to the prevention and treatment of obesity by inhibiting adipocyte differentiation and inhibiting the fat accumulation of adipocytes by autophagy.
또한, 유효성분으로 오배자 추출물 또는 이의 분획물은 경구 투여용 제형, 예를 들면 정제, 트로키제(troches), 로진지(lozenge), 수용성 또는 유성현탁액, 조제분말 또는 과립, 에멀젼, 하드 또는 소프트 캅셀, 시럽 또는 엘릭실제(elixirs)로 제제화된다. 정제 및 캅셀 등의 제형으로 제제화하기 위해 락토오스, 사카로오스, 솔비톨, 만니톨, 전분, 아밀로펙틴, 셀룰로오스 또는 젤라틴과 같은 결합제; 디칼슘 포스페이트와 같은 부형제; 옥수수 전분 또는 고구마 전분과 같은 붕괴제; 스테아린산 마그네슘, 스테아린산 칼슘, 스테아릴푸마르산 나트륨 또는 폴리에틸렌글리콜 왁스와 같은 윤활유가 함유된다. 캅셀제형의 경우는 상기에서 언급한 물질 이외에도 지방유와 같은 액체 담체를 함유한다. 또한, 상기 유효성분은 비경구로 투여할 수 있으며, 비경구 투여는 피하주사, 정맥주사, 근육 내 주사 또는 흉부 내 주사 주입방식에 의한다. 비경구 투여용 제형으로 제제화하기 위해서는 상기 조성물을 안정제 또는 완충제와 함께 물에서 혼합하여 용액 으로 제조하고 이를 앰플 또는 바이알의 단위 투여형으로 제제화한다.In addition, the gall bladder extract or fractions thereof as an active ingredient may be used in oral dosage forms, such as tablets, troches, lozenges, aqueous or oily suspensions, prepared powders or granules, emulsions, hard or soft capsules, Formulated in syrups or elixirs. Binders such as lactose, saccharose, sorbitol, mannitol, starch, amylopectin, cellulose or gelatin for formulation into formulations such as tablets and capsules; Excipients such as dicalcium phosphate; Disintegrants such as corn starch or sweet potato starch; Lubricants such as magnesium stearate, calcium stearate, sodium stearyl fumarate or polyethylene glycol wax. In the case of the capsule formulation, in addition to the substances mentioned above, it contains a liquid carrier such as fatty oil. In addition, the active ingredient can be administered parenterally, parenteral administration is by subcutaneous injection, intravenous injection, intramuscular injection or intrathoracic injection injection method. To formulate into a parenteral formulation, the composition is mixed in water with a stabilizer or buffer to prepare a solution, which is formulated in unit dosage forms of ampoules or vials.
상기 유효성분을 함유한 오배자 추출물 또는 이의 분획물의 유효투입량은 환자의 나이, 신체적 조건, 몸무게 등에 의해 다양화될 수 있지만, 일반적으로 10 내지 50 ㎎/㎏(몸무게)/1일 범위 내에서 투여하는 것이 바람직하다. 그리고, 1일 유효투입량 범위 내에서 하루에 한번 또는 하루에 여러 번 나누어 투입할 수 있다.The effective dose of the gall bladder extract or its fraction containing the active ingredient may vary according to the age, physical condition, weight, etc. of the patient, but is generally administered within the range of 10 to 50 mg / kg (weight) / day It is preferable. In addition, within a daily effective dosage range, it can be injected once or divided into several times a day.
또한, 건강식품이란, 상기 유효성분을 음료, 차류, 향신료, 껌, 과자류 등의 식품소재에 첨가하거나, 캅셀화, 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 있어 비만예방 식품 또는 비만치료 보조제로 섭취가 가능하다.In addition, the health food is a food prepared by adding the active ingredient to food materials such as beverages, teas, spices, gums, confectionery, capsules, powdered, suspensions, etc. Unlike the general medicine, it means that it is brought, but it is possible to take it as an anti-obesity food or an obesity treatment supplement because it has no merit such as side effects that may occur when taking the medicine for a long time.
본 발명의 건강식품은 오배자 추출물 또는 이의 분획물을 유효성분으로 포함하는데, 그 외에 다른 식품 또는 식품 첨가제와 함께 사용될 수 있다. 유효 성분과 기타 첨가제의 혼합량은 사용 목적(예방 또는 치료)에 따라 통상적인 범위 내에서 적절하게 결정될 수 있다.The health food of the present invention includes a gall bladder extract or a fraction thereof as an active ingredient, and may be used together with other food or food additives. The blending amount of the active ingredient with other additives may be appropriately determined within a conventional range depending on the purpose of use (prevention or treatment).
오배자 추출물 또는 이의 분획물은 전체 식품 조성물의 0.01 ∼ 100 중량% 포함될 수 있다. 그러나, 체중 조절 및 비만 예방을 목적으로 장기간 섭취하는 경우의 함량은 상기 범위 이하일 수 있으며, 안전성 및 부작용 면에서 아무런 문제가 없기 때문에 유효성분은 상기 범위 이상의 양으로도 사용될 수도 있다.The gall bladder extract or fractions thereof may comprise 0.01 to 100% by weight of the total food composition. However, the content in the case of long-term intake for the purpose of weight control and prevention of obesity may be below the above range, and since there is no problem in terms of safety and side effects, the active ingredient may be used in an amount above the above range.
본 발명의 조성물이 적용되는 식품의 종류에 특별한 제한은 없다. 상기 물질을 첨가할 수 있는 식품의 예로는 육류, 소세지, 빵, 쵸코렛, 캔디류, 스넥류, 과자류, 피자, 라면, 기타 면류, 껌류, 아이스크림류를 포함한 낙농제품, 각종 스프, 음료수, 차, 드링크제, 알코올음료 및 비타민 복합제 등이 있으며, 통상적인 의미에서의 건강식품을 모두 포함한다.There is no particular limitation on the kind of food to which the composition of the present invention is applied. Examples of the food to which the substance can be added include dairy products including meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gums, ice cream, various soups, drinks, tea, drinks, Alcoholic beverages and vitamin complexes, etc., includes all of the health food in the conventional sense.
본 발명의 건강음료는 통상의 음료와 같이 여러 가지 향미제 또는 천연 탄수화물 등을 추가 성분으로서 함유할 수 있다. 상기 천연 탄수화물에는 포도당, 과당 등의 모노사카라이드, 말토스, 슈크로스 등의 디사카라이드, 덱스트린, 사이클로덱스트린 등의 폴리사카라이드 및 자일리톨, 소르비톨, 에리트리톨 등의 당알콜이 포함된다. 감미제로서는 타우마틴, 스테비아 추출물 등의 천연 감미제, 또는 사카린, 아스파르탐 등의 합성 감미제 등을 사용할 수 있다. 상기 천연 탄수화물의 비율은 본 발명의 조성물 100 ㎖당 일반적으로 0.01 ~ 0.04 g, 바람직하게는 0.02 ~ 0.03 g이다.The health beverage of the present invention may contain various flavors or natural carbohydrates and the like as additional ingredients, as in general beverages. The natural carbohydrates include monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, polysaccharides such as dextrin and cyclodextrin and sugar alcohols such as xylitol, sorbitol and erythritol. As a sweetener, natural sweeteners, such as tautin and a stevia extract, or synthetic sweeteners, such as saccharin and aspartame, can be used. The proportion of the natural carbohydrate is generally from 0.01 to 0.04 g, preferably from 0.02 to 0.03 g per 100 ml of the composition of the present invention.
본 발명의 건강식품은 상기 성분 이외에 여러 가지 영양제, 비타민, 전해질, 풍미제, 착색제, 펙트산 및 그의 염, 알긴산 및 그의 염, 유기산, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알콜, 탄산음료에 사용되는 탄산화제 등을 함유할 수 있다. 그 밖에 본 발명의 건강식품은 천연 과일쥬스, 과일쥬스 음료 및 야채 음료의 제조를 위한 과육을 함유할 수 있다. 이러한 성분은 독립적으로 또는 조합하여 사용할 수 있다. 이러한 첨가제의 비율은 크게 중요하진 않지만 본 발명의 조성물 100 중량부에 대하여 0.01 ~ 0.1 중량부의 범위에서 선택되는 것이 일반적이다.In addition to the above ingredients, the health food of the present invention may contain various nutrients, vitamins, electrolytes, flavors, coloring agents, pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloidal thickeners, pH regulators, stabilizers, preservatives, glycerin, Alcohols, carbonating agents used in carbonated drinks, and the like. In addition, the health food of the present invention may contain flesh for preparing natural fruit juice, fruit juice beverage and vegetable beverage. These components can be used independently or in combination. The proportion of such additives is not critical but is generally selected in the range of 0.01 to 0.1 parts by weight with respect to 100 parts by weight of the composition of the present invention.
이하, 본 발명은 다음 실시예에 의거하여 더욱 상세히 설명하겠는바, 본 발명이 이에 한정되는 것은 아니다.Hereinafter, the present invention will be described in more detail based on the following examples, but the present invention is not limited thereto.
제조예 1: 오배자 추출물의 제조Preparation Example 1 Preparation of Mellitus Extract
제주도 일대의 국내산 오배자를 입수하여 건조시킨 후, 건조된 오배자를 음건 세절하고 세절한 오배자 1 kg을 메탄올 10 ~ 20 L로 실온에서 2 ~ 5회 반복 추출하여 그 추출물 232.5 g(수율 23.3%)을 얻었다[도 1]. After obtaining and drying domestic gallant in Jeju Island, dried dried gallant was dried in small shades and 1 kg of finely gallant was extracted 2 to 5 times at room temperature with 10-20 L of methanol to extract 232.5 g (yield 23.3%) of the extract. Obtained [FIG. 1].
제조예 2: 오배자 분획물의 제조Preparation Example 2 Preparation of Mellitus Fraction
상기 제조예 1에서 얻어진 추출물(메탄올 엑기스) 232.5 g을 증류수 2 L에 현탁한 후, 각각 동일 량의 노르말 헥산, 디클로로메탄, 에틸아세테이트로 차례로 분획한 다음 감압 농축하여 에틸아세테이트 분획물 106.52 g(수율 10.7%)을 얻었다[도 1]. 232.5 g of the extract (methanol extract) obtained in Preparation Example 1 was suspended in 2 L of distilled water, and then each fraction was partitioned with the same amount of normal hexane, dichloromethane, and ethyl acetate in that order, and then concentrated under reduced pressure. %) Was obtained [FIG. 1].
제조예 3: 유효성분 분리Preparation Example 3: Separation of Active Ingredients
상기 제조예 2에서 얻어진 에틸아세테이트 분획물 5 g을 실리카 비드(Silica beads)가 충진된 Glass Column(5 × 50 cm)에서 실리카 겔 컬럼 크로마토그래피(에틸아세테이트 : 메탄올 = 95:5 -> 80:20) 수행하여 7개의 분획으로 나누었다. 각각의 얻어진 분획 중 TLC 플레이트를 이용하여 탄닌산과 동일 스팟(spot)이 검출 되는 2~3 분획(Rf= 4.5, 헥산과 에틸아세테이트 3:7 용매에서)을 농축하여 완전 건조 후 MPLC(Combiflash RF, TELEDYNE ISCO) RediSep(130 gram vol.) flash column을 사용하여 헥산과 에틸아세테이트 9:1에서 2:8을 조성을 바꾸어 가며 정제를 진행하였다. 위의 소분획 100 mg을 분취용 HPLC를 옥타데실화 실리카가 충진된 역상컬럼을 이용하여 메탄올 : 물 = 20:80에서 70:30으로 전개하여 탄닌 분획물이 검출되는 20~35분 분획물(Rf= 4.5, 헥산과 에틸아세테이트 3:7 용매에서)을 다시 수집하여 감압 건조하였다. 이를 탄닌산(tannic acid) 표준품으로 분석하였을 때 탄닌류로서 99.5%로 분석되었다. 5 g of the ethyl acetate fraction obtained in Preparation Example 2 was subjected to silica gel column chromatography on a glass column (5 × 50 cm) filled with silica beads (ethyl acetate: methanol = 95: 5-> 80:20). And divided into 7 fractions. In each of the obtained fractions, TLC plates were used to concentrate 2 to 3 fractions (R f = 4.5, in hexane and ethyl acetate 3: 7 solvent) where the same spot as tannic acid was detected, followed by complete drying, followed by MPLC (Combiflash RF). , TELEDYNE ISCO) RediSep (130 gram vol.) Flash column using hexane and ethyl acetate from 9: 1 to 2: 8 to change the composition was purified. 100 mg of the above fractions were preparative HPLC was developed using a reversed phase column filled with octadecylated silica from methanol: water = 20:80 to 70:30 to detect the tannin fraction 20-35 minutes fraction (R f = 4.5, in hexane and ethyl acetate 3: 7 solvent) was collected again and dried under reduced pressure. When analyzed as a tannic acid standard, it was analyzed as 99.5% as tannins.
상기의 분리된 탄닌을 1.5N 염산용액에 용해하여 100 ℃ 수욕 상에서 30분간 가수분해한 이후 몰식자산을 HPLC로 분석하고, 동일한 탄닌을 메탄올에 용해하여 동량의 2M 설프릭산을 가하여 100 ℃ 수욕 상에서 30분간 메탄올 분해하여 메틸갈레이트를 분석하였다. 그 결과 염산 가수분해 시 탄닌으로부터 38.4%의 몰식자산이 확인되었으며, 메탄올 분해 시 13.1%의 몰식자산과 28.1%의 메틸갈레이트가 분석되었다. 따라서, 오배자의 유효분획인 에틸아세테이트 분획물의 탄닌 성분은 몰식자산이 결합되어 있는 다음 화학식 1로 표시되는 화합물로 확인되었다. The separated tannins were dissolved in 1.5 N hydrochloric acid solution and hydrolyzed for 30 minutes in a 100 ° C. water bath, and then analyzed by the HPLC. The same tannins were dissolved in methanol, and the same amount of 2M sulfic acid was added to the solution. Methylgallate was analyzed by methanol digestion for a minute. As a result, hydrochloric acid hydrolyzed 38.4% of ammonium from tannins, and methanol decomposition, 13.1%, and 28.1% methylgallate were analyzed. Therefore, the tannin component of the ethyl acetate fraction, which is the active fraction of the quintet, was identified as a compound represented by the following formula (1) in which a molar asset was combined.
[화학식 1][Formula 1]
상기 화학식 1에서, R1은 
제조예 4: 오배자 추출물의 제조Preparation Example 4 Preparation of Mellitus Extract
유효성분이 함유되어 있는 오배자 추출물에 대한 표준추출공정을 개발하기 위하여 오배자 1 kg을 분쇄하여 3 L의 50% 아세톤 수용액을 가하여 60 ℃에서 3시간 동안 천천히 교반하면서 추출하였다. 여기서 얻어진 여액 2.2L를 45 ℃에서 감압증류한 후 잔류된 수용액을 부탄올:톨루엔=8:2 용매 1 L를 가하여 액액분리하여 물층을 제거하였다. 이후 남은 용액을 감압 건조하여 물 1L:헥산 1L를 가하여 액액분리하여 헥산층을 제거하였다. 헥산층이 제거된 물층을 다시 부탄올:톨루엔=8:2 용매 1 L를 가하여 액액분리하여 상층의 부탄올:톨루엔 층을 모아서 완전히 감압 건조한다. 이 건조물에 50% 에탄올 200 mL을 가하여 완전용해 후 다시 감압 건조하고, 남은 분말에 95% 에탄올 200 mL을 가하여 완전용해 후 감압 건조를 하여 잔류용매를 완전히 제거하였다. In order to develop a standard extraction process for the five-fold extract containing the active ingredient, 1 kg of five-fold magnolia was pulverized, and 3 L of 50% acetone solution was added thereto, followed by extraction with slow stirring at 60 ° C. for 3 hours. 2.2 L of the filtrate obtained herein was distilled under reduced pressure at 45 ° C., and then the remaining aqueous solution was added with 1 L of butanol: toluene = 8: 2 solvent to separate the liquid and the water layer was removed. Thereafter, the remaining solution was dried under a reduced pressure, 1 L of water: 1 L of hexane was added thereto, and the liquid solution was separated to remove the hexane layer. The water layer from which the hexane layer was removed was added again with 1 L of butanol: toluene = 8: 2 solvent to separate the liquid, and the upper butanol: toluene layer was collected and dried under reduced pressure. 200 mL of 50% ethanol was added to the dried product, followed by complete dissolution, and dried under reduced pressure. 200 mL of 95% ethanol was added to the remaining powder, followed by complete dissolution and drying under reduced pressure to completely remove the residual solvent.
실시예 1 : 전지방세포 및 지방세포의 자가포식 활성 효과Example 1 effect of autophagy activity of all-cell and adipocyte
3T3-L1 전지방세포는 10% 혈청과 항생제가 포함된 DMEM 배지를 사용하였으 며, 5%의 이산화탄소의 공급과 37℃가 유지되는 배양기에서 배양하였다. 마우스의 전지방 세포주 3T3-L1은 ATCC(American Type Culture Collection)에서 구입하였고, DMEM 배양액, 트립신, FBS(Fetal bovine serum)와 BCS(Bovine calf serum)은 깁코(GibcoTM, Invitrogen corporation)에서 구입하였으며, 측정용 AdipoRedTM Assay Reagent는 Cambrex에서 구입하였다.3T3-L1 cells were used in DMEM medium containing 10% serum and antibiotics, and cultured in an incubator maintained at 37 ° C. with 5% carbon dioxide. I local cell line of mouse 3T3-L1 were purchased from ATCC (American Type Culture Collection), DMEM culture medium, trypsin, FBS (Fetal bovine serum) and BCS (Bovine calf serum) were purchased from Gibco (Gibco TM, Invitrogen corporation) AdipoRed ™ Assay Reagent for measurement was purchased from Cambrex.
1 × 104/ml의 3T3-L1 세포를 96 웰 플레이트에 분주해 세포가 100%로 증식될 때까지 배양하였으며, 지방세포로 분화시키기 위하여 MDI(0.5 mM 3-isobutyl-1-methyxanthine, 1 μM dexamethason, 10 ㎍/ml insulin, Sigma) 칵테일을 처리하였다. 이틀 후에 배지를 교체하고, 인슐린(Insulin)만을 같은 농도로 처리하였으며, 이틀 후 DMEM 배지에 10% 혈청만 포함된 배양액으로 배지를 교체하여 4일 동안 배양하였다. 분화 유도시의 자가포식 활성 시험을 위해 MDI 배지 처리 시 오배자 에틸아세테이트 분획물을 7.5 ~ 125 ㎍/ml의 농도로 처리하였으며, 분화 후의 자가포식 활성 시험을 위해 DMEM 배지 처리 시에 같은 농도로 처리하였다. 1 × 10 4 / ml of 3T3-L1 cells were dispensed into 96 well plates and cultured until the cells had grown to 100%. MDI (0.5 mM 3-isobutyl-1-methyxanthine, 1 μM) was used to differentiate into adipocytes. dexamethason, 10 μg / ml insulin, Sigma) cocktail. Two days later, the medium was replaced, and only insulin (Insulin) was treated at the same concentration. Two days later, the medium was replaced with a culture medium containing only 10% serum in the DMEM medium, followed by incubation for 4 days. For the autophagy activity test at the differentiation induction, the 5-fold ethyl acetate fraction was treated with MDI medium at a concentration of 7.5-125 μg / ml, and was treated at the same concentration during DMEM medium treatment for autophagy activity test after differentiation.
분화 유도시 4일, 분화 후 4일 동안 처리한 세포를 4% 파라포름알데하이드(Paraformaldehyde) 용액으로 15분간 고정시킨 뒤 인산완충용액(Phosphate buffered saline, PBS)으로 2번 세척하고, 0.05 mM 모노단실 카다베린(Monodansyl cadaverine, MDC)을 60분간 37℃에서 처리하였다. 다시 인산완충용액으로 2번 세척한 다음, internal standard로서 1 uM의 ethidium bromide를 10분간 처리한 후 디메틸설폭사이드(Dimethyl sulfoxide, DMSO)로 세포를 용해시킨 후 형광강도측정기 (Fluorometer, 모노단실 카다베린;excitation 356 nm/emission 545 nm, ethidium bromide;excitation 530 nm/emission 590 nm)로 측정하였으며, 형광현미경으로 관찰하였고, 농도별 자가탐식 활성값을 구했다[도 3 ~ 도 5]. After induction of differentiation, cells treated for 4 days and 4 days after differentiation were fixed with 4% Paraformaldehyde solution for 15 minutes, washed twice with Phosphate buffered saline (PBS), and 0.05 mM monosilicone. Cadaberine (Monodansyl cadaverine, MDC) was treated at 37 ° C. for 60 minutes. After washing twice with phosphate buffer solution, 1 uM of ethidium bromide was treated as an internal standard for 10 minutes, and then the cells were lysed with dimethyl sulfoxide (DMSO). Fluorometer (monosilyl cardaberine) Excitation 356 nm / emission 545 nm, ethidium bromide; Excitation 530 nm / emission 590 nm), was observed by a fluorescence microscope, and the self-detection activity value was determined for each concentration [Fig. 3 to 5].
이와 같이 측정한 결과는 다음 표 1에 나타내었다. The results thus measured are shown in Table 1 below.
상기 표 1에 나타낸 바와 같이, 오배자 분획물은 분화유도시 및 분화 후에 농도의존적으로 높은 수준의 자가탐식 활성을 나타내었다. As shown in Table 1, the gall bladder fraction showed a high level of autophagy activity in a concentration-dependent manner after differentiation and differentiation.
실시예 2 : 전지방세포 분화 억제 및 지방세포 지방축적 억제Example 2 Inhibition of Allergic Cell Differentiation and Adipocyte Adipose Accumulation
3T3-L1 전지방세포는 10% 혈청과 항생제가 포함된 DMEM 배지를 사용하였으며, 5%의 이산화탄소의 공급과 37℃가 유지되는 배양기에서 배양하였다. 마우스의 전지방 세포주 3T3-L1은 ATCC(American Type Culture Collection)에서 구입하였고, DMEM 배양액, 트립신, FBS(Fetal bovine serum)와 BCS(Bovine calf serum)은 깁코(GibcoTM, Invitrogen corporation)에서 구입하였으며, 측정용 AdipoRedTM Assay Reagent는 Cambrex에서 구입하였다.3T3-L1 battery cells were used in DMEM medium containing 10% serum and antibiotics, and cultured in an incubator maintained at 37 ° C. with 5% carbon dioxide. I local cell line of mouse 3T3-L1 were purchased from ATCC (American Type Culture Collection), DMEM culture medium, trypsin, FBS (Fetal bovine serum) and BCS (Bovine calf serum) were purchased from Gibco (Gibco TM, Invitrogen corporation) AdipoRed ™ Assay Reagent for measurement was purchased from Cambrex.
1 × 104/ml의 3T3-L1 세포를 96 웰 플레이트에 분주해 세포가 100%로 증식될 때까지 배양하였으며, 지방세포로 분화시키기 위하여 MDI(0.5 mM 3-isobutyl-1-methyxanthine, 1 μM dexamethason, 10 ㎍/ml insulin, Sigma) 칵테일을 처리하였다. 이틀 후에 배지를 교체하고, 인슐린(Insulin)만을 같은 농도로 처리하였으며, 이틀 후 DMEM 배지에 10% 혈청만 포함된 배양액으로 배지를 교체하여 4일 동안 배양하였다. 분화 억제 활성 시험을 위해 MDI 배지 처리 시 오배자 메탄올 추출물, 오배자 에틸아세테이트 분획물을 6.25 ~ 100 ㎍/ml의 농도로 처리하였으며, 지방축적 억제 활성 시험을 위해 DMEM 배지 처리 시에 같은 농도로 처리하였다. 1 × 10 4 / ml of 3T3-L1 cells were dispensed into 96 well plates and cultured until the cells had grown to 100%. MDI (0.5 mM 3-isobutyl-1-methyxanthine, 1 μM) was used to differentiate into adipocytes. dexamethason, 10 μg / ml insulin, Sigma) cocktail. Two days later, the medium was replaced, and only insulin (Insulin) was treated at the same concentration. Two days later, the medium was replaced with a culture medium containing only 10% serum in the DMEM medium, followed by incubation for 4 days. For the differentiation inhibitory activity test, the Methanol methanol extract and the Methanol ethyl acetate fraction were treated at a concentration of 6.25 to 100 µg / ml when treated with MDI medium, and treated at the same concentration when treated with DMEM medium for the fat accumulation inhibitory activity test.
총 8일 동안 분화시킨 지방세포를 4% 포름알데하이드(Formaldehyde) 용액으로 5시간 고정시킨 뒤 인산완충용액(Phosphate buffered saline, PBS)으로 2번 세척하고, 지방측정용 시약(AdipoRed)을 처리하였다. 10분 후 형광강도측정기 (Fluorometer, excitation 485 nm; emission 535 nm)로 측정하였으며, 형광현미경 (488 nm)로 관찰하였고, 각 분획물에 대한 EC50 값을 구했다. 본 발명에 따른 오배자 추출물이 지방세포 내 지방축적을 억제하는지 확인하기 위하여, 중성지방 (Triglyceride) 검출 킷트(TRIGLYZME assay kit, Shinyang, Seoul, Korea)를 사용하여 제조사에서 제공하는 실험 방법에 따라 수행하였다.Adipocytes differentiated for a total of 8 days were fixed with 4% formaldehyde (Formaldehyde) solution for 5 hours, washed twice with phosphate buffered saline (PBS), and treated with adipoRed. After 10 minutes, the result was measured by a fluorescence intensity meter (Fluorometer, excitation 485 nm; emission 535 nm), observed by fluorescence microscope (488 nm), and the EC 50 value of each fraction was obtained. In order to confirm whether the gall extract according to the present invention inhibits fat accumulation in adipocytes, triglyceride detection kit (TRIGLYZME assay kit, Shinyang, Seoul, Korea) was performed according to the experimental method provided by the manufacturer. .
이와 같이 측정한 결과는 다음 표 2에 나타내었다. The results thus measured are shown in Table 2 below.
추출물Methanol
extract
상기 표 2에 나타낸 바와 같이, 오배자 추출물(제조예 1), 에틸아세테이트 분획물(제조예 2)이 지방세포 분화 억제 및 분화된 지방세포의 지방축적을 억제하는 활성이 가장 높게 나타났다. As shown in Table 2, the quinine extract (Preparation Example 1) and ethyl acetate fraction (Preparation Example 2) showed the highest activity for inhibiting adipocyte differentiation and adipocyte accumulation of differentiated adipocytes.
실시예 3 : 오배자 추출물의 동물모델에서의 비만 치료 효능Example 3 Efficacy of Obesity Treatment in Animal Model of Mellitus Extract
체중 18~20g의 6주령 C57/BL 마우스(중앙실험동물에서 구입)를 10 개의 군으로 분배한 후 1군은 정상적인 사료를 공급하였으며, 나머지 9군은 45% 지방을 함유하고 있는 고지방 식이사료를 공급하였다. 6주 동안 비만을 유도한 후 1군과 2군은 음용수(D.W)를 처리하였고, 3군에는 제니칼(Xenical, 로슈) 2 mg/kg을, 4군은 리덕틸(Reductil, 애보트) 2.4 mg/kg, 5군~7군은 오배자 추출물을 농도별로 6주 동안 매일 경구 투여하였다(10 mg/kg, 20 mg/kg, 40 mg/kg). 또한, 8군~10군은 갈로탄닌을 농도별로 6주 동안 매일 경구 투여하였다(5 mg/kg, 10 mg/kg, 20 mg/kg). 각각에 대한 체중과 사료 섭취량은 1주에 한번 측정하였으며, 6주 후 각각 혈액을 채취하여, 혈중 중성지질 및 콜레스테롤, 중성지방의 양을 측정하였다. 또한, 치사한 후, 간과 부고환을 분리해 중성지질의 양을 측정하였다. Six-week-old C57 / BL mice weighing 18-20 g (purchased from a central laboratory animal) were divided into ten groups, and the first group fed normal diets, while the other nine groups received high-fat diets containing 45% fat. Supplied. After inducing obesity for 6 weeks,
이와 같이 측정한 결과는 다음 표 3 및 표 4에 나타내었다.The results thus measured are shown in Tables 3 and 4 below.
Comparison
상기 표 3에 나타낸 바와 같이, 오배자 추출물이 비만 유도 쥐에서 농도의존적으로 중성지방, 콜레스테롤, 저밀도지방단백 콜레스테롤의 증가를 억제하여 비만의 예방 및 치료 활성을 나타내었다. As shown in Table 3, the gall bladder extract inhibited the increase of triglycerides, cholesterol, low-density lipoprotein cholesterol concentration-dependently in the obesity-induced rats showed the prevention and treatment of obesity.
Comparison
메탄올
추출물 gallnut
Methanol
extract
상기 표 4에 나타낸 바와 같이, 오배자 추출물이 비만유도 쥐에서 농도의존적으로 간 지방 및 부고환 지방의 축적을 억제하여 비만의 예방 및 치료 활성을 나타내었다.As shown in Table 4, the gall bladder extract inhibited the accumulation of hepatic and epididymal fats in a concentration-dependent manner in obesity-induced rats, indicating the prevention and treatment of obesity.
실시예 4 : 다른 약재 추출물과의 비교Example 4 Comparison with Other Herbal Extracts
본 발명의 오배자 메탄올 추출물과 비만 억제 효과를 갖는다고 알려진 바나바(Banaba) 에탄올 추출물[웰니스바나바, 통신구매]의 유효성분의 함량을 다음과 같이 분석하였고, 그 결과를 다음 표 5에 나타내었다.Methanol extract of the present invention and the active ingredient content of Banaba ethanol extract [Wellness Banaba, communication purchase] known to have an obesity inhibitory effect was analyzed as follows, and the results are shown in Table 5 below.
1. 직접 분석: 각각의 추출물 50mg을 정밀히 달아 10mL 이동상에 넣고 1분간 초음파 처리하여 용해 후 원심분리하여 상등액을 고속액체크로마토그래프법으로 분석하였다.1. Direct analysis: 50mg of each extract was precisely weighed, placed in a 10mL mobile phase, sonicated for 1 minute, dissolved, and centrifuged, and the supernatant was analyzed by high performance liquid chromatography.
2. 가수분해: 각각의 추출물 50mg을 정밀히 달아 1.5M HCl 용액 10mL에 용해하여 밀봉 가능한 시험관에 넣고 완전히 밀봉후 100 ℃ 수욕상에서 30분간 가수분해한 후 원심분리하여 상등액을 고속액체크로마토그래프법으로 분석하였다.2. Hydrolysis: 50mg of each extract was precisely weighed, dissolved in 10mL of 1.5M HCl solution, placed in a sealable test tube, completely sealed, hydrolyzed for 30 minutes in a 100 ° C water bath, and centrifuged to analyze the supernatant by high-performance liquid chromatography method. It was.
3. 메탄올분해(methanolysis): 각각의 추출물 50mg을 정밀히 달아 5mL 메탄올에 용해 후 동량의 2M 황산을 가하여 섞어준후 밀봉 가능한 시험관에 넣고 완전히 밀봉 후 100 ℃ 수욕상에서 30분 메탄올분해한 후 원심분리하여 상등액을 고속액체크로마토그래프법으로 분석하였다.3. Methanolysis: Accurately weigh 50mg of each extract, dissolve in 5mL methanol, add 2M sulfuric acid in the same amount, mix, put into a sealable test tube, seal completely, methanolyze for 30 minutes in 100 ℃ water bath, and centrifuge. Was analyzed by high performance liquid chromatography.
고속액체크로파토그래프법의 기기조건은 다음과 같다.The equipment conditions of the high-speed liquid chromatograph method are as follows.
오배자 메탄올 추출물과 상기 바나바 추출물에 대해 3T3-L1 분화 억제와 지방 축척 억제에 대한 비교시험을 통하여 본 발명의 오배자 추출물이 기존에 지방분화 억제 및 항비만 효과가 알려진 바나바 추출물과의 유효한 함량을 비교함으로써 더욱 효과가 우수함을 입증하기 위하여 실시예 2와 동일한 방법으로 시험하였다. 그 결과, 3T3-L1 분화 억제 및 지방축적 억제 효과를 다음 표 6에 나타내었다. Through the comparative tests on the inhibitory effect of 3T3-L1 differentiation and fat accumulation on the Methanol extract of Banbae extract and Banaba extract, by comparing the effective content of the Banbae extract of the present invention with the Banaba extract known to inhibit fat differentiation and anti-obesity effect In order to prove more effective, it was tested in the same manner as in Example 2. As a result, the effects of 3T3-L1 differentiation inhibition and fat accumulation inhibition are shown in Table 6 below.
상기 표 6에 나타냈듯이, 본 발명의 오배자 추출물은 기존의 바나바 추출물에 비해 3~4배의 비만 억제 효능을 가지고 있음을 확인할 수 있었다.As shown in Table 6, it was confirmed that the gall bladder extract of the present invention has an obesity inhibitory effect of 3 to 4 times that of the conventional Banaba extract.
실시예 5: 독성시험Example 5: Toxicity Test
본 발명의 유효성분인 오배자 메탄올 추출물과 에틸아세테이트 분획물 각각에 대하여 독성실험을 다음과 같이 수행하였다. Toxicity experiments were performed for each of the extract of Methanol methanol and ethyl acetate, the active ingredient of the present invention.
오배자 메탄올 추출물과 에틸아세테이트 분획물 각각을 0.5% 소듐 카르복시메틸 셀룰로오스(sodium carboxymethly cellulose)에 용해하고 물로 희석한 후 이를 마우스(군당 10마리)에 각각 0, 4, 20, 100, 500 ㎎/㎏이 되도록 경구 투여한 다음 7일간 관찰하였다. 오배자 추출물과 에틸아세테이트 분획물로 인하여 사망한 쥐는 없었으며, 이후 7일간 사망하는 쥐는 없었다. Methanol methanol extract and ethyl acetate fractions were dissolved in 0.5% sodium carboxymethly cellulose, diluted with water, and then added to mice (10 per group) to 0, 4, 20, 100, 500 mg / kg, respectively. Observation was performed for 7 days after oral administration. No rats died due to gall bladder extract and ethyl acetate fraction, and no mice died for 7 days thereafter.
제제예 1: 정제의 제조Formulation Example 1 Preparation of Tablet
유효성분으로 오배자 추출물과 에틸아세테이트 분획물 또는 이의 혼합물 15 mg이 함유된 정제는 다음과 같은 방법으로 제조한다. Tablets containing 15 mg of gallnut extract and ethyl acetate fraction or mixtures thereof as an active ingredient are prepared by the following method.
유효성분 250 g을 락토오스 175.9 g, 감자전분 180 g 및 콜로이드성 규산 32 g과 혼합하였다. 이 혼합물에 10% 젤라틴 용액을 첨가시킨 후, 분쇄해서 14 메쉬체를 통과시켰다. 이것을 건조시키고 여기에 감자전분 160 g, 활석 50 g 및 스테아린산 마그네슘 5 g을 첨가해서 얻은 혼합물을 정제로 만들었다. 250 g of active ingredient was mixed with 175.9 g of lactose, 180 g of potato starch, and 32 g of colloidal silicic acid. 10% gelatin solution was added to the mixture, which was then ground and passed through a 14 mesh sieve. It was dried and the mixture obtained by adding 160 g of potato starch, 50 g of talc and 5 g of magnesium stearate was made into a tablet.
제제예 2: 캅셀제의 제조Formulation Example 2: Preparation of Capsule
유효성분(오배자 추출물, 에틸아세테이트 분획물 또는 이의 혼합물) 500 ㎎을 경질 젤라틴 캅셀에 충전하여 캅셀제를 제조하였다.500 mg of the active ingredient (gallic extract, ethyl acetate fraction or mixture thereof) was filled into hard gelatin capsules to prepare a capsule.
제제예 3 : 음료 제조Formulation Example 3: Beverage Preparation
유효성분(오배자 추출물, 에틸아세테이트 분획물 또는 이의 혼합물) 500 ㎎을 적당량의 물에 용해시킨 후에 보조성분으로서 비타민 C, 교미제로서 구연산, 구연산나트륨, 올리고당을 적당량 가하고, 보존제로서 적당량의 나트륨벤조에이트를 가한 후에 물을 가하여 전량을 100 ㎖로 만들어 음료용 조성물을 제조하였다. 이때 타우린이나 마이오 이노시톨, 엽산, 판토텐산 등을 단독으로 혹은 함께 첨가할 수 있다.After dissolving 500 mg of the active ingredient (gallnut extract, ethyl acetate fraction or mixture thereof) in an appropriate amount of water, vitamin C as an auxiliary component, citric acid, sodium citrate, oligosaccharides as a coagent, and an appropriate amount of sodium benzoate are added as a preservative. After the addition, water was added to make 100 ml of the total amount to prepare a beverage composition. At this time, taurine, myo-inositol, folic acid, pantothenic acid, etc. may be added alone or together.
도 1은 본 발명의 오배자 추출물로부터 에틸아세테이트 분획물을 얻는 과정 을 나타낸 것이다. Figure 1 shows the process of obtaining the ethyl acetate fraction from the gall of the present invention.
도 2는 본 발명의 유효성분이 함유되어 있는 오배자 추출물 제조공정을 나타낸 것이다. Figure 2 shows the manufacturing process of the gallengja extract containing the active ingredient of the present invention.
도 3은 본 발명의 유효성분이 함유되어 있는 오배자 분획물의 지방세포 분화 유도 4일 후의 자가탐식 활성을 나타낸 그래프이다. Figure 3 is a graph showing the
도 4는 본 발명의 유효성분이 함유되어 있는 오배자 분획물의 지방세포 분화 4일 후의 자가탐식 활성을 나타낸 그래프이다.Figure 4 is a graph showing the
도 5는 본 발명의 유효성분이 함유되어 있는 오배자 추출물의 지방세포 분화 4일 후의 자가탐식 활성을 나타낸 그림이다.Figure 5 is a diagram showing the
도 6은 비만유도 동물모델에서 유효성분이 함유되어 있는 오배자 추출물이 체중 증가를 억제하는 활성을 나타낸 그래프이다. Figure 6 is a graph showing the activity of inhibiting weight gain of the galleng extract containing the active ingredient in obesity-induced animal model.
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| KR20190108359A (en) | 2018-03-14 | 2019-09-24 | 원광대학교산학협력단 | Inhibitory effect of galla rhois extract on colorectal metastasis |
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| KR101361536B1 (en) * | 2011-12-27 | 2014-02-13 | 세명대학교 산학협력단 | Isolation method of Antiobese Constituents from Yukeuigambitang |
| KR20190108359A (en) | 2018-03-14 | 2019-09-24 | 원광대학교산학협력단 | Inhibitory effect of galla rhois extract on colorectal metastasis |
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