KR100967813B1 - A composition comprising the extract of Raphani semen as an active ingredient showing anti-obesity and anti-hyperlipidemia activity - Google Patents
A composition comprising the extract of Raphani semen as an active ingredient showing anti-obesity and anti-hyperlipidemia activity Download PDFInfo
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- KR100967813B1 KR100967813B1 KR1020080025256A KR20080025256A KR100967813B1 KR 100967813 B1 KR100967813 B1 KR 100967813B1 KR 1020080025256 A KR1020080025256 A KR 1020080025256A KR 20080025256 A KR20080025256 A KR 20080025256A KR 100967813 B1 KR100967813 B1 KR 100967813B1
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- Prior art keywords
- fat
- obesity
- extract
- hyperlipidemia
- blood
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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
- A61K2236/331—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using water, e.g. cold water, infusion, tea, steam distillation, decoction
Abstract
본 발명은 나복자 (Raphani semen) 추출물을 유효성분으로 함유하는 고지혈증 또는 비만의 예방 및 치료용 조성물에 관한 것으로, 상세하게는 본 발명의 나복자 물 추출물은 생체 내 실험 (in vivo)을 통해 고지방 사료를 섭취한 실험동물의 체중, 난소 주위 지방의 중량, 혈중 지질함량, 혈중 렙틴 및 아디포넥틴 함량을 유의적으로 감소하였으므로, 상기 조성물은 고지혈증 또는 비만의 예방 및 치료용 약학조성물 또는 건강기능식품으로 유용하게 이용할 수 있다.The invention of the moth ( Raphani semen ) relates to a composition for the prevention and treatment of hyperlipidemia or obesity containing the extract as an active ingredient, in detail the moth extract extract of the present invention in vivo ( in In vivo ) significantly reduced the body weight, the weight of the fat around the ovary, the blood lipid content, blood leptin and adiponectin content in the high-fat diet, the composition is a pharmaceutical composition for the prevention and treatment of hyperlipidemia or obesity or It can be usefully used as a dietary supplement.
나복자, 고지혈증, 비만 Moxa, hyperlipidemia, obesity
Description
본 발명은 나복자 추출물을 유효성분으로 함유하는 고지혈증 또는 비만의 예방 및 치료용 약학조성물 또는 건강기능식품에 관한 것이다.The present invention relates to a pharmaceutical composition or health functional food for the prevention and treatment of hyperlipidemia or obesity containing the extract of Nakbokja as an active ingredient.
[문헌 1] Schoen FJ et al ., Robbins pathologic basis of disease, 5th ed., pp.473-484, 1994Schoen FJ et al . , Robbins pathologic basis of disease, 5th ed., Pp. 473-484, 1994
[문헌 2] 국승래 외, 가정의학회지, 18(3), pp.317-327, 1997[Ref. 2] Kook Seung-rae et al., Journal of Family Medicine, 18 (3) , pp.317-327, 1997
[문헌 3] Kunitomi M, et al ., Int . J. Obes . Relat . Metab . Disord ., 26, pp.361-9, 2002Document 3 Kunitomi M, et al . , Int . J. Obes . Relat . Metab . Disord . , 26 , pp.361-9, 2002
[문헌 4] Mitchell M, et al ., Reproduction, 130, pp.583-97, 2005[4] Mitchell M, et al . , Reproduction , 130 , pp.583-97, 2005
[문헌 5] 중약대사전, 김창민 외, pp.715-718, 1997[Reference 5] Chinese Medicine Dictionary, Chang Min Kim, pp.715-718, 1997
[문헌 6] Sahai A, et al ., Am . J. Physiol . Gastrointest . Liver Physiol ., 287, pp.G1035-43, 2004Document 6 Sahai A, et al . , Am . J. Physiol . Gastrointest . Liver Physiol . , 287 , pp.G1035-43, 2004
고지혈증 (hyperlipidemia)은 혈액 속의 지질성분이 보통 이상으로 증가된 상태를 말한다. 혈청지질의 주요 성분을 콜레스테롤, 중성지질, 인지질 및 유리지방산 등의 지용성물질로 구성되어 있으며, 이들 지질 물질 중 어느 것이 주로 증가하느냐에 따라 고콜레스테롤혈증 (hypercholesterinemia), 고중성지질혈증 (hypertriglyceridemia) 등으로 불리운다. 혈청 내 콜레스테롤 및 중성지질의 증가가 고지혈증의 가장 일반적인 원인으로 취급되고 있는데 과다한 지방질의 축적으로 혈액순환장애 및 미세순환부전을 일으키고, 이로 인하여 죽상동맥경화증, 허혈성 심질환, 뇌경색, 고혈압, 비만, 당뇨병 등을 초래할 수 있다 (Schoen FJ et al ., Robbins pathologic basis of disease, 5th ed., pp.473-484, 1994).Hyperlipidemia is a condition in which lipid components in the blood are increased more than usual. The major components of serum lipids are composed of fat-soluble substances such as cholesterol, triglycerides, phospholipids, and free fatty acids, and depending on which of these lipids increases, hypercholesterinemia, hypertriglyceridemia, etc. It is called. Increased serum cholesterol and triglycerides are the most common causes of hyperlipidemia. Accumulation of excess fat causes blood circulation disorders and microcirculation failure, resulting in atherosclerosis, ischemic heart disease, cerebral infarction, hypertension, obesity and diabetes. May result (Schoen FJ et al . , Robbins pathologic basis of disease, 5th ed., Pp. 473-484, 1994).
콜레스테롤은 주로 간에서 생성되며, 지단백 (lipoprotein)이라는 작고 둥근 입자형태로 혈액 중에 존재하게 되는데, 이 지단백이 콜레스테롤을 우리 몸 곳곳으로 운반한다. 지단백에는 저밀도지단백 (low density lipoprotein, LDL) 및 고밀도지단백 (high density lipoprotein, HDL) 두 종류가 있으며, 고밀도지단백은 다른 조직에서 간으로 콜레스테롤을 운반하기 때문에 고밀도지단백이 많으면 혈관 등에서 콜레스테롤이 제거되며, 반면 저밀도지단백은 간에서 주로 생성되어 인체의 다른 조직으로 콜레스테롤을 운반하므로 저밀도지단백이 많으면 혈관에 콜레스테롤이 많이 쌓여서 동맥경화가 촉진되며, 혈중 콜레스테롤의 약 70%는 나쁜 콜레스테롤인 저밀도지단백으로 존재한다.Cholesterol is produced mainly in the liver and is present in the blood in the form of small round particles called lipoproteins, which carry cholesterol throughout the body. There are two types of lipoproteins, low density lipoprotein (LDL) and high density lipoprotein (HDL), and because high density lipoproteins carry cholesterol from other tissues to the liver, a lot of high-density lipoprotein removes cholesterol from blood vessels. On the other hand, low-density lipoproteins are mainly produced by the liver and transport cholesterol to other tissues of the human body, so a lot of low-density lipoproteins accumulate a lot of cholesterol in blood vessels to promote arteriosclerosis, and about 70% of blood cholesterol is present as low-density lipoproteins, which are bad cholesterol.
실제적으로 콜레스테롤은 인체의 기능을 정상적으로 유지시키는 데 필수적인 구성 성분이며, 세포를 만드는데 꼭 필요한 영양소이고, 부신피질 호르몬, 남성 호르몬, 여성 호르몬 등 여러 가지 호르몬의 재료가 되는 성분이며, 담즙을 만드는 재료가 된다. 또한 콜레스테롤은 생체막의 구성성분인 동시에 호르몬 합성의 출발물질로 쏘이는 등 인체에 반드시 필요한 영양소이다. 그러나 콜레스테롤 과다 섭취시 혈관 내에 축적되어 심장계 질환을 유발하는 것으로 알려져 있으며, 아직까지는 저콜레스테롤 식이요법 외에는 예방할 수 있는 방법이 없으며, 콜레스테롤 저하제 등의 약품 복용이 효과는 있으나, 콜레스테롤 합성효소의 작용억제에 따른 간 기능 장애와 같은 부작용을 유발하는 등의 이유로 인하여 사용이 극히 제한적이다.In fact, cholesterol is an essential ingredient for normal functioning of the human body, a nutrient necessary for making cells, and a component of various hormones such as corticosteroids, male hormones, and female hormones. do. In addition, cholesterol is a nutrient necessary for the human body, such as being a component of a biological membrane and being shot as a starting material for hormonal synthesis. However, excessive cholesterol intake is known to accumulate in the blood vessels and cause heart disease, and there is no preventive method except low-cholesterol diet, and taking drugs such as cholesterol-lowering drugs is effective. Use is extremely limited due to reasons such as causing side effects such as liver dysfunction.
고지혈증은 혈중 콜레스테롤이나 중성지방이 높은 상태로 손등에 노란색 결절이 생기고 발목과 손목 주위에 결절이 발생한다. 그리고 눈꺼풀에 결절이 발생하며 홍채 주위에 하얀 고리가 생기는 증상이 나타난다. 80년대 이후 과식과 동물성 지방의 섭취, 운동부족, 흡연과 과음, 스트레스 등으로 인해 고지혈증 환자가 늘고 있다.Hyperlipidemia is a condition that is high in blood cholesterol or triglycerides with yellow nodules on the back of the hand and nodules around the ankles and wrists. Nodules develop on the eyelids and white rings appear around the iris. Since the 1980s, hyperlipidemia has increased due to overeating, animal fat intake, lack of exercise, smoking, heavy drinking and stress.
고지혈증 치료제는 지나친 혈중 지방, 특히 콜레스테롤과 중성지방의 수치를 낮추기 위해 사용된다. 지질 대사에 사용되는 주요 약들은 스타틴, 담즙산 차단제, 피브르산 유도체 등이 있다 이 약들은 각각 다른 기전으로 작용한다. 고지혈증 치료제의 선택은 증가된 지단백의 종류에 따라서 이들 약제를 복합적으로 사용하기도 하며, 이들은 매일 경구로 장기간 복용이 필요하다. 이러한 약들은 콜레스테롤과 혈중농도를 효과적으로 떨어뜨리지만, 부작용을 가지고 있다는 단점이 있다. 스타 틴의 경우 구역, 두통, 복통과 설사나 변비가 나타날 수 있어 근육에 염증을 유발할 수 있고 담즙산 차단제는 비타민 A, D, K의 장 흡수가 떨어질 수 있으므로, 이들 비타민 보충이 필요하다. 그리고 피브리산 유도체는 신장 질환, 간질환 또는 담낭 질환에는 부적합한 약이다. 따라서 이들 제제를 대신할 의약품 및 천연물이 함유된 기능성 식품 등의 개발에 대한 요구가 커지고 있다 (국승래 외, 가정의학회지, 18(3), pp.317-327, 1997).Hyperlipidemia drugs are used to lower levels of excess blood fat, especially cholesterol and triglycerides. Major drugs used in lipid metabolism include statins, bile acid blockers, and fibric acid derivatives. These drugs act by different mechanisms. The choice of therapeutic agents for hyperlipidemia may be a combination of these drugs, depending on the type of lipoproteins that have been increased, and they require long-term oral daily use. These drugs effectively lower cholesterol and blood levels, but have the disadvantage of having side effects. Statins can cause nausea, headache, abdominal pain and diarrhea or constipation, which can cause muscle inflammation, and bile acid blockers can reduce the intestinal absorption of vitamins A, D, and K. And fibric acid derivatives are unsuitable drugs for kidney disease, liver disease or gallbladder disease. Therefore, there is a growing demand for the development of medicines and functional foods containing natural products in place of these preparations (Kook Seung-rae et al., Journal of Family Medicine, 18 (3) , pp.317-327, 1997).
비만은 체지방이 지나치게 축적되는 상태로 키에 따라 계산되는 건강한 체중의 최대치보다도 적어도 20%이상 체중이 초과하는 경우에 비만으로 여긴다. 비만은 장기와 관절에 압박을 주기 때문에 등의 통증, 엉덩이와 무릎의 통증, 그리고 숨이 가빠지는 것 등 여러 가지 건강문제의 원인이 되며, 관상동맥 질환, 뇌졸중, 고혈압과 같은 잠재적으로 치명적일 수 있는 질환들의 위험을 증가시키고 우울증과 같은 심리적인 문제도 불러온다. 또한 비만은 다양한 만성질환의 위험을 증가시킨다. 비만한 사람들은 혈중 콜레스테롤 수치가 높으며 이로 인해 동맥의 내벽에 지방이 축적되는 동맥경화증의 위험을 증가시키며, 동맥경화는 고혈압과 관상동맥 질환의 원인이 된다. 동맥 혈전증과 혈전에 의해 혈관이 막히는 색전증도 자주 나타나며, 담석증의 위험도 더 크고, 당뇨병에도 더 잘 걸리는 경향이 있다. 유방암과 자궁암 같은 여러 암 역시 비만한 사람에게 더 흔하다. 과중한 몸무게는 관절들을 압박하는데, 특히 엉덩이와 무릎의 골관절염은 비만한 사람들에게 흔하다. 호흡성 질환으로 수면 무호흡 역시 비만한 사람들과 관련이 있다. 현재 비만을 판단하는 가장 일반적인 기준은 복부 지방의 양 및 분포로 알려져 있다 (Kunitomi M, et al ., Int . J. Obes . Relat . Metab . Disord ., 26, pp.361-9, 2002).Obesity is regarded as obesity when the body fat is excessively accumulated and the body weight exceeds at least 20% more than the maximum value of the healthy weight calculated according to the height. Obesity puts pressure on organs and joints, causing a number of health problems, including back pain, hip and knee pain, and shortness of breath, and potentially fatalities such as coronary artery disease, stroke, and high blood pressure. It increases the risk of illnesses and brings psychological problems such as depression. Obesity also increases the risk of various chronic diseases. Obese people have high blood cholesterol levels, which increases the risk of atherosclerosis, which accumulates fat in the lining of the arteries, which causes high blood pressure and coronary artery disease. Arterial thrombosis and embolism in which blood vessels are clogged by blood clots often appear, and the risk of cholelithiasis is greater, and diabetes tends to be more likely. Several cancers, such as breast and uterine cancers, are also more common in obese people. Excessive weight compresses joints, especially osteoarthritis of the hips and knees is common in obese people. Sleep apnea as a respiratory disease is also associated with obese people. The most common criterion for determining obesity is now known as the amount and distribution of abdominal fat (Kunitomi M, et. al . , Int . J. Obes . Relat . Metab . Disord . , 26 , pp. 361-9, 2002).
전 세계적으로 비만 환자는 계속해서 증가하고 있으며, 비만의 원인 규명을 위한 노력이 경주되고 있으며, 이러한 노력의 결과 운동 등의 감소에 따른 에너지 항상성의 이상에 의해 초래되는 것으로 알려져 있다. 치료방법으로는 식단조절과 운동이 필수적이며 식욕 억제 약물을 사용해 볼 수 있으나 부작용 때문에 거의 추천되지 않는다. 그러므로 예로부터 사용되어 인체에 무해함이 입증되어 온 천연물 추출물을 이용한 치료제의 경우, 기존 치료제에 의한 내성이나 안전성 문제를 극복할 수 있다 (Mitchell M, et al ., Reproduction, 130, pp.583-97, 2005).Obesity patients are increasing all over the world, and efforts are being made to determine the cause of obesity. As a result of these efforts, it is known that the cause of obesity is caused by abnormality of energy homeostasis due to the reduction of exercise. As a treatment, diet and exercise are essential, and appetite suppressants can be used, but due to side effects, it is rarely recommended. Therefore, in the case of therapeutics using natural extracts, which have been used for a long time and have been proved to be harmless to humans, resistance or safety problems caused by existing therapeutics can be overcome (Mitchell M, et. al . , Reproduction , 130 , pp.583-97, 2005).
렙틴 (leptin)은 식욕조절호르몬으로 알려져 있으며, 이외에도 다양한 역할을 하는 것으로 밝혀지고 있다. ob/ob 마우스에서 지방축적량이 증가할수록 렙틴의 혈중농도는 증가하며, 비만환자의 신체는 렙틴에 대한 저항성을 띠게 된다고 알려져 있다. Leptin (leptin) is known as appetite control hormone, it has been found to play a variety of roles in addition. It is known that as fat accumulation increases in ob / ob mice, blood levels of leptin increase, and the body of obese patients becomes resistant to leptin.
지방조직은 1990년대 후반까지만 해도 필요없는 것으로 인식되었으나, 지방조직이 에너지 대사와 비만에 핵심적 역할을 하는 아디포넥틴 (adiponectin)을 분비한다는 사실이 밝혀지면서, 지방조직의 중요성에 대한 인식이 고조되어 왔다. 지방축적량이 증가하면 아디포넥틴 분비량이 감소하며, 당뇨병, 심장질환, 암이 발명할 위험을 증가시키는 좋은 지표가 된다. 또한 아디포넥틴은 혈장에 다량으로 함유되어 있으면서 순환하기 때문에 이를 지표로 삼아 지방대사 이상을 검사하기도 하며, 염증억제 물질로 작용한다는 연구보고도 있었다. 따라서 아디포넥틴과 렙틴에 대해서 비만과 관련하여 많은 연구가 진행되고 있다.Adipose tissue was recognized as not necessary until the late 1990s, but the discovery of adiponectin, which plays a key role in energy metabolism and obesity, has raised awareness of the importance of adipose tissue. Increased fat accumulation decreases adiponectin secretion and is a good indicator of increased risk of developing diabetes, heart disease, and cancer. In addition, since adiponectin is circulated in a large amount of plasma, it has been used as an indicator to test for fat metabolism abnormalities, and there is a research report that acts as an inflammation inhibitor. Therefore, many studies on adiponectin and leptin related to obesity have been conducted.
나복자는 십자화과에 속한 식물로 무 (Raphanus sativus L.)의 여문 종자이다. 말린 종자는 타원형이거나 둥근 난형과 비슷한데 조금 편평하며 길이는 약 3 mm, 너비는 2.5 mm이다. 표면은 적갈색이며 한쪽에 세로 홈이 몇 개 있고 한쪽 끝에 밑씨가 있다. 밑씨는 갈색이고 둥근 점 모양으로 도드라져 있다. 확대경으로 관찰하면 씨 전체에 그물무늬가 촘촘히 있다. 질은 단단하고 쪼개면 황백색 혹은 누런 알맹이가 보이고 알맹이에 정유가 있다. 여름과 가을에 종자가 여물면 포기를 베어 햇볕에 말렸다가 손으로 비벼 씨를 빼내어, 잡물을 제거한 후 햇볕에 말린 후 한약재로 사용한다 (중약대사전, 김창민 외, pp.715, 1997).The Locust is a plant belonging to the Cruciferaceae radish ( Raphanus sativus L. ) is the seed of a woman. Dried seeds are oval or round ovate, slightly flat, about 3 mm long and 2.5 mm wide. The surface is reddish brown with several longitudinal grooves on one side and a seed on one end. The underside is brown and raised in round dots. When viewed with a magnifying glass, there is a tight net pattern throughout the seeds. The vagina is hard and split into yellowish white or yellowish kernels, and the kernels have essential oils. When the seeds grow in summer and autumn, they give up the seeds and dry them in the sun, then remove the seeds by hand, remove the miscellaneous goods, dry them in the sun, and use them as herbal medicines (Chinese medicine dictionary, Kim Chang-min, pp.715, 1997).
나복자에는 항균물질이 들어 있어 포도상 구7균과 대장균에 대하여 뚜렷한 억제 작용을 하고 동심성, 백선균 등의 피부진균에 대한 항진균작용 등의 약리작용을 가지고 있다. 그리고 기가 치밀어 오르는 증세를 치료하고 호흡을 가라앉히며 소화를 돕고 가래를 삭히는 효능이 있으며 해수로 인한 기관지 천식, 식적기체 (食積氣滯), 가슴이 답답하고 더부룩한 증상, 이질에 의한 이급후중을 치료하는데 나복자가 처방된다 (중약대사전, 김창민 외, pp.716-718, 1997). 근래에 들어, 나복자 추출물 또는 일부 구성성분이 강력한 항돌연변이 활성, 항균, 항고혈압 및 항염작용을 나타내는 것으로 보고되었으나, 항고지혈증 또는 항비만 효과에 대한 연구는 수행되지 않았다.The moths contain antibacterial substances, which have distinct inhibitory effects against Staphylococcus aureus and Escherichia coli, and have pharmacological effects such as concentricity and ringworm fungus against skin fungi. It is effective in treating the symptoms of rising sun, decreasing breathing, helping digestion, and cutting out phlegm, and bronchial asthma caused by sea water, food gas, chest swelling and bloating, and dysentery due to dysentery. Nabokja is prescribed for the treatment (Chinese medicine dictionary, Kim Chang-min et al., Pp.716-718, 1997). Recently, moth extracts or some components have been reported to exhibit potent antimutagenic activity, antibacterial, antihypertensive and anti-inflammatory effects, but no studies on antihyperlipidemia or anti-obesity effects have been conducted.
따라서 본 발명자들은 한방에서 약재로 사용되어져 온 천연물 성분 중에 나복자 물 추출물을 이용하여 고지방 사료를 섭취한 동물실험을 통하여 체중, 난소 주위 지방의 중량, 혈중 지질함량, 혈중 렙틴 및 아디포넥틴 함량을 유의적으로 감 소하여 항고지혈증 또는 항비만 효과를 확인하여 본 발명을 완성하였다.Therefore, the present inventors significantly increased the weight, weight of ovarian fat, blood lipid content, blood leptin and adiponectin content through animal experiments in which high-fat feed was taken using the extract of nabokgi water from the natural ingredients that have been used as herbal medicine. To reduce the antihyperlipidemia or anti-obesity effect was completed the present invention.
상기 목적을 달성하기 위하여, 본 발명은 나복자 추출물을 유효성분으로 함유하는 고지혈증 또는 비만의 예방 및 치료용 약학조성물을 제공한다.In order to achieve the above object, the present invention provides a pharmaceutical composition for the prevention and treatment of hyperlipidemia or obesity, containing the extract of Nakbokja as an active ingredient.
또한, 본 발명은 나복자 추출물을 유효성분으로 함유하는 고지혈증 또는 비만의 예방 및 개선용 건강기능식품을 제공한다.In addition, the present invention provides a health functional food for the prevention and improvement of hyperlipidemia or obesity containing the extract of Nakbokja as an active ingredient.
본원에서 정의되는 나복자는 십자화과의 무 (Raphanus sativus L.), 갯무 (Raphanus sativus var. hortensis for. raphanistroides Makino) 또는 서양무아재비 (Raphanus raphanistrum L.), 바람직하게는 무 (Raphanus sativus L.)의 건조된 종자를 포함한다.The moths, as defined herein, are radish ( Raphanus) sativus L.), gaetmu (Raphanus sativus var. hortensis for. raphanistroides Makino) , or non-Western Buttercup (Raphanus raphanistrum L. ), preferably radish ( Raphanus sativus L. ), dried seeds.
본원에서 정의되는 추출물은 정제수를 포함한 물, 탄소수 1 내지 4의 저급알코올 또는 이들의 혼합용매로부터 선택된 용매, 바람직하게는 물에 가용한 추출물을 포함한다.Extracts as defined herein include water, including purified water, lower alcohols having 1 to 4 carbon atoms or solvents selected from mixed solvents thereof, preferably extracts soluble in water.
이하, 본 발명을 상세히 설명한다.Hereinafter, the present invention will be described in detail.
본 발명의 나복자 추출물은 하기와 같이 제조될 수 있다. 건조된 나복자를 정제수를 포함한 물, 탄소수 1 내지 4의 저급알코올 또는 이들의 혼합용매로부터 선택된 용매, 바람직하게는 물로 0℃ 내지 120℃, 바람직하게는 100℃에서 100분 내지 1일, 바람직하게는 150분 동안 추출하는 제 1단계; 이를 여과농축 및 동결 건 조시키는 제 2단계를 포함하는 제조방법을 통해 본 발명의 나복자 추출물을 수득할 수 있다.The moth extract of the present invention can be prepared as follows. The dried moth is a solvent selected from water including purified water, a lower alcohol having 1 to 4 carbon atoms or a mixed solvent thereof, preferably water, 0 to 120 ° C, preferably 100 to 100 minutes to 1 day, preferably Extracting for 150 minutes; Through the manufacturing method comprising the second step of filtration concentration and freeze-drying it can be obtained the extract of the present invention.
본 발명은 상기의 제조방법으로 얻어진 나복자의 추출물을 유효성분으로 함유하는 고지혈증 또는 비만의 예방 및 치료용 약학조성물을 제공한다.The present invention provides a pharmaceutical composition for the prevention and treatment of hyperlipidemia or obesity, which contains the extract of the moths obtained by the above method as an active ingredient.
또한, 본 발명은 상기의 제조방법으로 얻어진 나복자 추출물을 유효성분으로 함유하는 고지혈증 또는 비만의 예방 및 개선용 건강기능식품을 제공한다.In another aspect, the present invention provides a health functional food for the prevention and improvement of hyperlipidemia or obesity, containing the extract of the Nakbokja obtained by the above production method as an active ingredient.
본 발명의 나복자 추출물을 함유하는 고지혈증 또는 비만의 예방 및 치료를 위한 약학조성물은, 조성물 총 중량에 대하여 상기 나복자를 0.1 내지 50 중량% 포함한다.The pharmaceutical composition for the prevention and treatment of hyperlipidemia or obesity containing the moth extract of the present invention comprises 0.1 to 50% by weight based on the total weight of the composition.
본 발명의 나복자 추출물을 함유하는 약학조성물은 약학적 조성물의 제조에 통상적으로 사용하는 적절한 담체, 부형제 및 희석제를 더 포함할 수 있다. The pharmaceutical composition containing the extract of Nakbokgi of the present invention may further include suitable carriers, excipients and diluents commonly used in the preparation of pharmaceutical compositions.
본 발명의 나복자 추출물을 함유하는 약학조성물은, 각각 통상의 방법에 따라 산제, 과립제, 정제, 캡슐제, 현탁액, 에멀젼, 시럽, 에어로졸 등의 경구형 제형, 외용제, 좌제 및 멸균 주사용액의 형태로 제형화하여 사용될 수 있다. 화합물을 함유하는 조성물에 함유될 수 있는 담체, 부형제 및 희석제로는 락토즈, 덱스트로즈, 수크로스, 솔비톨, 만니톨, 자일리톨, 에리스리톨, 말티톨, 전분, 아카시아 고무, 알지네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실리케이트, 셀룰로즈, 메틸 셀룰로즈, 미정질 셀룰로스, 폴리비닐 피롤리돈, 물, 메틸히드록시벤조에이트, 프로필히드록시벤조에이트, 탈크, 마그네슘 스테아레이트 및 광물유를 들 수 있다. 제제화할 경우에는 보통 사용하는 충진제, 증량제, 결합제, 습윤제, 붕해제, 계면활 성제 등의 희석제 또는 부형제를 사용하여 조제된다. 경구투여를 위한 고형제제에는 정제, 환제, 산제, 과립제, 캡슐제 등이 포함되며, 이러한 고형제제는 상기 화합물에 적어도 하나 이상의 부형제, 예를 들면, 전분, 칼슘카보네이트 (calcium carbonate), 수크로스 (sucrose) 또는 락토오스 (lactose), 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 단순희석제인 물, 리퀴드 파라핀 이외에 여러 가지 부형제, 예를 들면 습윤제, 감미제, 방향제, 보존제 등이 포함될 수 있다. 비경구 투여를 위한 제제에는 멸균된 수용액, 비수성용제, 현탁제, 유제, 동결건조 제제, 좌제가 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 (macrogol), 트윈 (tween) 61, 카카오지, 라우린지, 글리세로제라틴 등이 사용될 수 있다.The pharmaceutical composition containing the extract of Nakbokjagi of the present invention may be prepared in the form of powder, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, oral formulations, external preparations, suppositories, and sterile injectable solutions according to conventional methods. Can be formulated and used. Carriers, excipients and diluents which may be contained in the composition containing the compound include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium Silicates, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil. When formulated, diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrating agents and surfactants are usually used. Solid form preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, which include at least one excipient such as starch, calcium carbonate, sucrose ( It is prepared by mixing sucrose or lactose, gelatin and the like. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Oral liquid preparations include suspensions, solvents, emulsions, and syrups, and may include various excipients, such as wetting agents, sweeteners, fragrances, and preservatives, in addition to commonly used simple diluents such as water and liquid paraffin. . Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, suppositories. As the non-aqueous solvent and suspending agent, propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like can be used. As the base of the suppository, witepsol, macrogol, tween 61, cacao butter, laurin butter, glycerogelatin and the like can be used.
본 발명의 나복자 추출물의 사용량은 환자의 나이, 성별, 체중에 따라 달라질 수 있으나, 0.1 내지 100 mg/kg을 일일 1회 내지 수회 투여할 수 있다. 또한 그 투여량은 투여경로, 질병의 정도, 성별, 체중, 나이 등에 따라서 증감될 수 있다. 따라서 상기 투여량은 어떠한 면으로든 본 발명의 범위를 한정하는 것은 아니다.The amount of the extracts of the present invention may vary depending on the age, sex, and weight of the patient, but 0.1 to 100 mg / kg may be administered once to several times daily. The dosage may also be increased or decreased depending on the route of administration, the severity of the disease, sex, weight, age, and the like. Therefore, the above dosage does not limit the scope of the present invention in any aspect.
상기 약학조성물은 쥐, 생쥐, 가축, 인간 등의 포유동물에 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 (intracerebroventricular) 주사에 의해 투여될 수 있다.The pharmaceutical composition may be administered to various mammals such as mice, mice, livestock, humans, and the like. All modes of administration can be expected, for example by oral, rectal or intravenous, intramuscular, subcutaneous, intrauterine dural or intracerebroventricular injection.
본 발명은 나복자 추출물을 유효성분으로 포함하는 고지혈증 또는 비만의 예방 및 개선용 건강기능식품을 제공한다. 이를 첨가할 수 있는 식품으로는 각종 식품류, 분말, 과립, 정제, 캡슐, 시럽제, 음료, 껌, 차, 비타민 복합제, 건강기능성 식품류 등이 있다.The present invention provides a dietary supplement for the prevention and improvement of hyperlipidemia or obesity, including the extract of Nakbokja as an active ingredient. Foods to which it may be added include various foods, powders, granules, tablets, capsules, syrups, beverages, gums, teas, vitamin complexes, and health functional foods.
또한, 고지혈증 또는 비만의 예방 효과를 목적으로 식품 또는 음료에 첨가될 수 있다. 이때 식품 또는 음료 중의 나복자 추출물의 양은 전체 식품 중량의 0.01 내지 15중량%로 가할 수 있으며, 건강 기능성 음료 조성물은 100 ml 기준으로 0.02 내지 5 g, 바람직하게는 0.3 내지 1 g의 비율로 가할 수 있다.It may also be added to foods or beverages for the purpose of preventing hyperlipidemia or obesity. At this time, the amount of the extract from the Nakbokja in the food or beverage may be added to 0.01 to 15% by weight of the total food weight, the health functional beverage composition may be added in a ratio of 0.02 to 5 g, preferably 0.3 to 1 g based on 100 ml. .
본 발명의 건강 기능성 음료 조성물은 지시된 비율로 필수 성분으로서 상기 추출물을 함유하는 외에는 다른 성분에는 특별한 제한이 없으며, 통상의 음료와 같이 여러 가지 향미제 또는 천연 탄수화물 등을 추가성분으로서 함유할 수 있다. 상술한 천연 탄수화물의 예는 모노사카라이드, 예를 들어, 포도당, 과당 등; 디사카라이드, 예를 들어 말토스, 슈크로스 등; 및 폴리사카라이드, 예를 들어 덱스트린, 시클로덱스트린 등과 같은 통상적인 당 및 자일리톨, 소르비톨, 에르트리톨 등의 당알콜이다. 상술한 것 이외의 향미제로서 천연 향미제 (타우마틴, 스테비아 추출물) 및 합성 향미제 (사카린, 아스파르탐 등)를 유리하게 사용할 수 있다. 상기 천연 탄수화물의 비율은 본 발명의 조성물 100 ml 당 일반적으로 약 1 내지 20 g, 바람직하게는 약 5 내지 12 g이다.The health functional beverage composition of the present invention is not particularly limited to other ingredients except for containing the extract as an essential ingredient in the indicated ratio, and may contain various flavors or natural carbohydrates as additional ingredients, such as ordinary drinks. . Examples of the above-mentioned natural carbohydrates include monosaccharides such as glucose, fructose and the like; Disaccharides such as maltose, sucrose and the like; And sugars such as conventional sugars such as polysaccharides such as dextrin, cyclodextrin and the like and xylitol, sorbitol, erythritol. As flavoring agents other than those mentioned above, natural flavoring agents (tautin, stevia extract) and synthetic flavoring agents (saccharin, aspartame, etc.) can be advantageously used. The proportion of such natural carbohydrates is generally about 1 to 20 g, preferably about 5 to 12 g per 100 ml of the composition of the present invention.
상기 외에 본 발명의 추출물은 여러 가지 영양제, 비타민, 광물 (전해질), 합성 풍미제 및 천연 풍미제 등의 풍미제, 착색제 및 중진제 (치즈, 초콜릿 등), 펙트산 및 그의 염, 알긴산 및 그의 염, 유기산, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알콜, 탄산 음료에 사용되는 탄산화제 등을 함유할 수 있다. 그 밖에 본 발명의 추출물은 천연 과일주스 및 야채 음료의 제조를 위한 과육을 함유할 수 있다. 이러한 성분은 독립적으로 또는 조합하여 사용할 수 있다. 이러한 첨가제의 비율은 그렇게 중요하지는 않지만 본 발명의 추출물 100 중량부 당 0 내지 약 20 중량부의 범위에서 선택되는 것이 일반적이다In addition to the above, the extract of the present invention is a variety of nutrients, vitamins, minerals (electrolytes), synthetic flavors and natural flavors, such as flavoring agents, coloring and neutralizing agents (such as cheese, chocolate), pectic acid and salts thereof, alginic acid and its Salts, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohols, carbonation agents used in carbonated beverages, and the like. In addition, the extract of the present invention may contain a pulp for the production of natural fruit juices and vegetable drinks. These components can be used independently or in combination. The proportion of such additives is not so critical but is usually selected in the range of 0 to about 20 parts by weight per 100 parts by weight of the extract of the present invention.
상기에서 설명한 바와 같이, 본 발명에서 나복자 추출물은 고지방 사료를 먹인 마우스를 통해 경구투여한 결과, 혈중 총 콜레스테롤, 중성지질, 저밀도지단백, 혈중 렙틴 및 아디포넥틴의 함량을 효과적으로 저해했으며, 고밀도지단백의 함량을 증가시킴으로써 항고지혈증 및 항비만 효과를 가짐을 확인하고 이를 이용하여 고지혈증과 비만 억제효과를 지닌 약학조성물 또는 건강기능식품으로 유용하게 이용할 수 있다.As described above, in the present invention, the extract of Nabokjab was administered orally through high-fat feed mice, effectively inhibiting blood total cholesterol, triglycerides, low density lipoprotein, blood leptin and adiponectin, and the high density lipoprotein content. By increasing the anti-hyperlipidemia and anti-obesity effect has been confirmed that by using it can be useful as a pharmaceutical composition or health functional food with a hyperlipidemia and obesity inhibitory effect.
이하, 본 발명을 상세히 설명한다. 단, 하기 실시예, 참고예 및 실험예는 본 발명을 예시하는 것일 뿐, 본 발명의 내용이 이에 의해 한정되는 것은 아니다.Hereinafter, the present invention will be described in detail. However, the following Examples, Reference Examples and Experimental Examples are merely illustrative of the present invention, but the content of the present invention is not limited thereto.
실시예Example 1. One. 나복자의Mob 물 추출물의 제조 Preparation of Water Extract
나복자는 대원약업사 (대구, 한국)에서 구입하여 물로 세척하여 음건 후 사용하였다. 나복자의 건조 중량 200 g을 취하여 1.3 L 정제수에 100℃에서 150분간 전탕한 후, 여과 농축하여 동결건조를 통해 본 발명의 시료 (이하 “RS"이라 명명함)를 수득하여 (최종수율 12.09%) 하기 실험에 사용하였다.Nabok was purchased from Daewon Pharmaceutical Co., Ltd. (Daegu, Korea), washed with water and used after drying. 200 g of dry weight of moth was taken, and hot water was poured into 1.3 L purified water at 100 ° C. for 150 minutes, and then concentrated by filtration to obtain a sample of the present invention (hereinafter referred to as “RS”) by lyophilization (final yield 12.09%). It was used for the following experiment.
실시예Example 2. 2. 나복자의Mob 메탄올 추출물의 제조 Preparation of Methanol Extracts
나복자는 대원약업사 (대구, 한국)에서 구입하여 물로 세척하여 음건 후 사용하였다. 나복자의 건조 중량 200 g을 취하여 1.2 L 메탄올에 침지하여 실온에서 5일 방치한 후, 감압농축하여 본 발명의 시료 (이하 “RS-M"이라 명명함)를 수득하여 (최종 수율 6.78%) 하기 실험에 사용하였다.Nabok was purchased from Daewon Pharmaceutical Co., Ltd. (Daegu, Korea), washed with water and used after drying. Take 200 g of dry weight of moths, soak in 1.2 L methanol, leave at room temperature for 5 days, and concentrate under reduced pressure to obtain a sample of the present invention (hereinafter referred to as “RS-M”) (final yield 6.78%) It was used for the experiment.
참고예Reference Example 1. 실험동물 및 1. Experimental animals and 실험식이의Experimental 준비 Ready
120 마리의 성숙한 암컷 ICR 마우스 (SLC, Japan)를 7일간 실험실 환경에 적응 시킨 후 사용하였으며, 6일동안 하기 표 1의 고지방 사료를 공급 후 체중을 기본으로 40% beef tallow가 함유된 AIN-76A 고지방 사료 (Dyets, PA, USA)와 유사한 적응성을 보이는 약 반수의 실험동물을 선정하여 하기 실험에 사용하였다. 정상사료 대조군에서는 실험 기간 동안 하기 표 1의 정상 사료를 공급하였고 고지방 사료는 약물 투여 개시 6일전부터 84일동안 계속 공급하였다. 대조약물로 사용된 메트 포민 (metformin)은 경구용 혈당강하제로 현재 비만을 포함한 대사증후군 치료 후보 물질의 약효 검색시 가장 널리 사용되는 비교 약물 중 하나이며, 와코사 (Wako chemicals, Osaka, Japan)에서 구입하였다. 120 adult female ICR mice (SLC, Japan) were used after 7 days of acclimatization in the laboratory environment. AIN-76A containing 40% beef tallow based on body weight after feeding the high fat diet of Table 1 for 6 days. About half of the animals showing similar adaptability to the high fat diet (Dyets, PA, USA) were selected and used in the following experiments. In the normal feed control group, the normal feed of Table 1 was supplied during the experiment period, and the high fat feed was continuously supplied for 84 days from 6 days before the start of drug administration. Metformin, used as a reference drug, is an oral hypoglycemic agent and is currently one of the most widely used comparative drugs in the search for the efficacy of candidates for treating metabolic syndrome including obesity.Wako Chemicals, Osaka, Japan Purchased.
실험은 하기 표 2에 나타난 바와 같이, 그룹당 10 마리씩의 실험동물을 사용하였으며, 메트포민 (metformin) 250 mg/kg 투여군 및 상기 실시예 1에서 수득한 RS 125, 250 및 500 mg/kg의 용량을 84일 동안 각각 경구 투여하였다.As shown in Table 2 below, 10 experimental animals were used per group, and
(g/kg diet)Normal feed
(g / kg diet)
(g/kg diet)High fat feed
(g / kg diet)
대조군Normal feed
Control
(10 ml/kg)Purified water
(10 ml / kg)
투여군Metaformin
실험예Experimental Example 1. 형태학적 변화 1. Morphological Change
상기 참고예 1의 실험 동물 체중은 투여일, 7, 21, 35, 49, 63, 77, 83 및 실험결과 표 3 및 도 1A에 나타난 바와 같이, 체중변화는 모든 고지방 사료 일인 고지방 사료 공급 7일후부터, 메트포민 (metformin), RS 500 및 250 mg/kg 투대조군에 비해 유의성 있게 체중이 증가하였다.Experimental animal body weight of Reference Example 1 is administered on
Experimental group
Weight gain (g)
고지방 사료에 비하여 통계적 유의성 # p<0.01Statistical significance compared to normal feed * p <0.01;
Statistical significance # p <0.01 compared to high fat diet
1-2. 난소주위 지방 중량 측정1-2. Ovarian fat mass measurement
상기 참고예 1의 실험 동물의 최종 희생일에 난소 주위 지방을 분리한 다음 습 중량 (g)을 측정하였으며, 체중에 따른 지방 중량의 변화를 줄이기 위해 체중 당 지방 중량을 산출하였다. On the final sacrificial day of the experimental animal of Reference Example 1 was isolated the fat around the ovary and then measured the wet weight (g), fat weight per body weight was calculated in order to reduce the change in fat weight according to the weight.
실험결과, 표 4에 나타난 바와 같이 고지방사료 공급 대조군에서는 정상대조군에 비해 유의성 있는 지방 중량의 증가가 인정되었으나, 모든 투여군에서는 고지방사료 공급 대조군에 비해 유의성 있는 난소주위 지방 중량이 감소됨을 확인할 수 있었다.As a result, as shown in Table 4, a significant increase in fat weight was recognized in the high fat feed control group as compared to the normal control group, but it was confirmed that the significant ovarian fat weight decreased in all the administration groups as compared to the high fat feed control group.
Experimental group
고지방 사료에 비하여 통계적 유의성 # p<0.01Statistical significance compared to normal feed * p <0.01;
Statistical significance # p <0.01 compared to high fat diet
실험예Experimental Example 2. 혈중 지질의 함량 측정 2. Determination of blood lipid content
2-1. 혈중 총 콜레스테롤의 함량 측정2-1. Determination of total cholesterol in blood
상기 참고예 1의 실험동물을 최종 희생일에 마취 하에서 복대정맥으로부터 약 1 ml의 혈액을 채취하여 3000 rpm으로 원심분리하여 혈청을 분리하였다. 이후 혈청 중에서 총 콜레스테롤, 중성지질, LDL 및 HDL의 함량을 혈액자동분석장치 (AU400, olympus, Japan)를 이용하여 각각 측정하였다.About 1 ml of blood was collected from the abdominal vein under anesthesia on the last sacrifice day and centrifuged at 3000 rpm to separate serum from the experimental animal of Reference Example 1. Since then, the total cholesterol, triglycerides, LDL and HDL content in serum were measured using an automatic blood analyzer (AU400, olympus, Japan).
실험결과, 도 1B에 나타난 바와 같이, 혈청 중 총 콜레스테롤 수치의 변화는 고지방사료 공급 대조군에서는 정상사료 대조군에 비해 유의성 있게 증가하였으며, RS 모든 투여군에서 고지방사료 공급 대조군에 비해 유의성 있게 감소함을 확인 할 수 있었다. As a result, as shown in FIG. 1B, the change in the total cholesterol level in serum was significantly increased in the high fat feed control group compared to the normal feed control group. Could.
2-2. 혈중 중성지질의 함량 측정2-2. Determination of blood triglyceride content
상기 실험예 2-1과 동일한 방법으로 혈청 중 중성지질의 함량을 측정한 결과, 도 2에 나타난 바와 같이 같다 고지방 사료 공급 대조군에서는 정상사료 대조군에 비해 유의성 있게 혈중 중성지질의 함량이 증가한 반면에, RS 모든 투여군에서는 고지방 사료 공급 대조군에 비해 유의성 있게 감소함을 확인할 수 있었다.As a result of measuring the content of the neutral lipid in the serum by the same method as Experimental Example 2-1, as shown in Figure 2, in the high-fat feed control group, the content of blood triglyceride increased significantly compared to the normal feed control group, The administration group was found to be significantly reduced compared to the high fat diet control group.
2-3. 혈중 저밀도지질 (LDL) 및 고밀도지질 (HDL)의 함량 측정2-3. Determination of Low Density Lipid (LDL) and High Density Lipid (HDL) Levels in Blood
상기 실험예 2-1과 동일한 방법으로 혈청 중 저밀도지단백 및 고밀도지단백의 함량을 측정한 결과, 도 3에 나타난 바와 같이 혈청 중 LDL 함량은 고지방 사료 공급 대조군에서는 정상사료 대조군에 비해 유의성 있게 증가하였으나, RS 모든 투여군에서는 고지방 사료 공급 대조군에 비해 유의성 있게 감소함을 확인할 수 있었다.As a result of measuring the low-density lipoprotein and high-density lipoprotein content in serum by the same method as Experimental Example 2-1, as shown in FIG. 3, the LDL content in the serum was significantly increased in the high fat feeding control group compared to the normal feed control group. All the RS groups were significantly decreased compared to the high fat diet control group.
또한, 도 4에 나타난 바와 같이 혈청 중 HDL 함량의 변화는 고지방사료 공급 대조군에서는 정상사료 대조군에 비해 유의성 있게 감소하였으나, RS 모든 투여군에서는 고지방 사료 공급 대조군에 비해 유의성 있게 증가함을 확인할 수 있었다.In addition, as shown in FIG. 4, the HDL content in the serum was significantly decreased in the high fat feed control group compared to the normal feed control group, but it was confirmed that the RS was significantly increased in all the administration groups.
실험예 3. 혈중 렙틴 (leptin) 및 아디포넥틴 (adiponectin)의 함량 측정Experimental Example 3 Determination of Leptin and Adiponectin in Blood
3-1. 혈중 렙틴 (leptin)의 함량 측정3-1. Determination of Leptin Content in Blood
상기 참고예 1의 실험동물을 최종 희생일에 마취하에 복대정맥으로부터 혈액을 채취하여 3000 rpm으로 원심분리하여 혈청을 분리하였다. 실험동물의 혈중 렙틴 (leptin)의 함량은 Sahai 등의 방법 (Sahai A, et al ., Am . J. Physiol . Gastrointest. Liver Physiol., 287, pp.G1035-43, 2004)에 따라 방사면역측정법 킷트 (radioimmunoassay kit, Linco Research, MO, USA)를 사용하여 측정하였다. Blood was collected from the abdominal vein under anesthesia on the final sacrifice day and centrifuged at 3000 rpm to separate serum. Blood leptin content in experimental animals was determined by Sahai et al. (Sahai A, et. al . , Am . J. Physiol . Gastrointest. Liver Physiol. , 287 , pp. G1035-43, 2004), using a radioimmunoassay kit (radioimmunoassay kit, Linco Research, MO, USA).
실험결과, 도 5에 나타난 바와 같이 고지방 사료 공급 대조군에서는 정상사료 대조군에 비해 유의성 있는 혈중 렙틴 함량이 증가하였으나, RS 모든 투여군에서는 고지방 사료 공급 대조군에 비해 유의성 있게 감소함을 확인할 수 있었다.As a result, as shown in Figure 5, the high-fat feeding control group showed a significant increase in blood leptin content compared to the normal feed control group, it was confirmed that all the RS administration significantly reduced compared to the high-fat feeding control group.
3-2, 혈중 아디포넥틴 (adiponectin)의 함량 측정3-2, Determination of the content of adiponectin in the blood
상기 참고예 1의 실험동물을 최종희생일에 마취하에 복대정맥으로부터 혈액을 채취하여 3000 rpm으로 원심분리하여 혈청을 분리하였다. 실험동물의 혈중 아디포넥틴 (adiponectin)의 함량은 ELISA 킷트 (Otsukapharm, Japan)를 이용하여 측정하였다. Blood was collected from the abdominal vein under anesthesia on the last sacrificial day and centrifuged at 3000 rpm to separate serum. The content of adiponectin in the blood of experimental animals was measured using an ELISA kit (Otsukapharm, Japan).
실험결과, 도 6에 나타난 바와 같이 아디포넥틴 함량의 변화는 고지방사료 공급 대조군에서는 정상사료 대조군에 비해 유의성 있게 증가하였으나, RS 모든 투여군에서는 고지방 사료 공급 대조군에 비해 유의성 있게 감소함을 확인 할 수 있었다.As a result, as shown in FIG. 6, the adiponectin content was significantly increased in the high fat feed control group compared to the normal feed control group, but it was confirmed that the RS was significantly decreased in the high fat feed control group.
실험예 4. 조직병리학적 변화Experimental Example 4 Histopathological Change
조직병리학적 변화를 관찰하기 상기 참고예 1의 실험동물의 난소주위 지방 및 복벽에 부착된 지방 조직을 적출한 다음, 포매를 실시한 다음 3~4 ㎛의 절편을 준비하고, 헤마톡실린-에오신 (Hematoxylin-Eosin) 염색하에서 광학현미경을 이용하여 이상 병변 유무를 관찰하였다. 난소 주위 지방 및 복벽 지방 세포의 평균 직경을 자동영상 분석장치 (DMI-300, Image Processing, DMI, Korea)를 이용하여 산출하였다. Observing Histopathological Changes The periovarian fat and the adipose tissue attached to the abdominal wall of the experimental animal of Reference Example 1 were removed, embedded, and then sections of 3 to 4 μm were prepared, and hematoxylin-eosin ( Hematoxylin-Eosin) staining was observed using an optical microscope. Average diameters of peri-ovarian fat and abdominal wall fat cells were calculated using an automatic image analyzer (DMI-300, Image Processing, DMI, Korea).
실험결과 도 7에 나타난 바와 같이, 난소주위 지방 세포의 평균 직경 변화은 고지방사료 공급 대조군에서는 정상사료 대조군에 비해 유의성 있게 난소주위 지방세포 직경이 증가되었으며, RS 모든 투여군에서는 고지방사료 공급 대조군에 비해 유의성 있게 감소됨을 확인할 수 있었다. As shown in FIG. 7, the mean diameter change of the ovarian adipocytes was significantly increased in the ovarian adipocyte diameter in the high fat feed control group compared to the normal feed control group. It was confirmed that the decrease.
또한 도 8에 나타난 바와 같이, 축적된 복벽 지방의 두께 변화는 고지방사료 공급 대조군에서는 정상사료 대조군에 비해 유의성 있게 복벽지방 두께의 증가되었으며, RS 모든 투여군에서는 고지방사료 공급 대조군에 비해 유의성 있는 감소됨을 확인할 수 있었다.In addition, as shown in Figure 8, the thickness change of the accumulated abdominal wall fat was significantly increased in the abdominal wall fat thickness in the high-fat feed control group compared to the normal feed control, it was confirmed that significantly reduced compared to the high-fat feed supply control group in all RS Could.
복벽 지방세포의 평균 직경 변화는 도 9에 나타난 바와 같이 고지방사료 공급 대조군에서는 정상사료 대조군에 비해 유의성 있는 복벽 지방세포 직경의 증가가 인정되었고, RS 모든 투여군에서는 고지방사료 공급 대조군에 비해 유의성 있게 감소됨을 확인할 수 있었다.As shown in FIG. 9, the mean diameter change of abdominal wall adipocytes was found to be significantly increased in abdominal wall adipocyte diameter in the high fat feed control group compared to the normal feed control group, and significantly decreased in all RS groups compared to the high fat feed supply control group. I could confirm it.
도 10에 나타난 바와 같이 정상사료 대조군(a), 고지방사료 공급 대조군(b) 및 메트포민 (metformin) 250 mg/kg 투여군(c)의 난소 주위 지방의 조직학적 소견은 고지방사료 공급 대조군에서 현저한 지방세포 비대가 관찰되었으나 메트포민 (metformin) 투여군에서는 현저히 감소하였으며, 도 11에 나타난 바와 같이, RS 500(a), 250(b) 및 125 mg/kg 투여군(c)의 난소 주위 지방의 조직학적 소견은 고지방사료 공급에 의해 초래되는 지방세포 비대가 RS 투여에 의해 농도의존적으로 억제됨을 관찰할 수 있었다. As shown in FIG. 10, histologic findings of the ovarian fat of the normal feed control group (a), the high fat feed control group (b), and the
또한, 도 12에 나타난 바와 같이 정상사료 대조군(a), 고지방 사료 공급 대조군(b) 및 메트포민 투여군(c)의 복벽지방의 조직학적 소견으로 고지방 사료 공급 대조군에서는 난소주위 지방과 유사하게 현저한 지방세포 비대가 관찰되었으나, 메트포민 투여군에서 현저하게 감소되었으며, 도 13에 나타난 바와 같이 RS 500(a), 250(b) 및 125 mg/kg 투여군(c)의 복벽지방의 조직학적 소견으로 고지방사료 공급에 의해 초래되는 지방세포 비대가 RS 투여에 의해 농도의존적으로 억제됨을 관찰할 수 있었다. In addition, as shown in Figure 12 histological findings of abdominal wall fat of the normal feed control (a), high-fat feeding control (b) and metformin-administered group (c) in the high-fat feeding control, the fat cells remarkably similar to the surrounding ovary fat Hypertrophy was observed, but significantly decreased in metformin-treated group, and as shown in FIG. 13, histological findings of abdominal wall fat in RS 500 (a), 250 (b) and 125 mg / kg-administered group (c) showed high fat feed supply. It was observed that adipocyte hypertrophy caused by concentration was inhibited concentration-dependently by RS administration.
본 발명의 추출물을 포함하는 조성물의 제제예를 설명하나, 본 발명은 이를 한정하고자 함이 아닌 단지 구체적으로 설명하고자 함이다.Examples of the formulation of the composition comprising the extract of the present invention will be described, but the present invention is not intended to limit it, but is intended to explain in detail only.
제제예Formulation example 1. One. 산제의Powder 조제 pharmacy
RS 20 mg
유당 100 mg
탈크 10 mg
상기의 성분들을 혼합하고 기밀포에 충진하여 산제를 조제한다.The above ingredients are mixed and filled in an airtight cloth to prepare a powder.
제제예Formulation example 2. 정제의 제조 2. Preparation of Tablets
RS 10 mg
옥수수 전분 100 mg
유당 100 mg
스테아린산 마그네슘 2 mg2 mg magnesium stearate
상기의 성분들을 혼합한 후 통상 정제의 제조방법에 따라서 타정하여 정제를 제조한다.After mixing the above components, tablets are usually prepared by tableting according to the method for preparing tablets.
제제예Formulation example 3. 캅셀제의 제조 3. Manufacture of capsule
RS 10 mg
결정성 셀룰로오스 3 mg3 mg of crystalline cellulose
락토오스 14.8 mgLactose 14.8 mg
마그네슘 스테아레이트 0.2 mgMagnesium Stearate 0.2 mg
통상의 캡슐제 제조방법에 따라 상기의 성분을 혼합하고 젤라틴 캡슐에 충진하여 캡슐제를 제조한다.According to a conventional capsule preparation method, the above ingredients are mixed and filled into gelatin capsules to prepare capsules.
제제예Formulation example 4. 주사제의 제조 4. Preparation of injections
RS 10 mg
만니톨 180 mg
주사용 멸균 증류수 2974 mgSterile distilled water for injection 2974 mg
Na2HPO4·12H2O 26 mg Na 2 HPO 4 · 12H 2 O 26 mg
통상 주사제의 제조방법에 따라 1 앰플당 (2 ml) 상기의 성분 함량으로 제조한다.It is usually prepared in the above ingredient content per ampoules (2 ml) according to the preparation method of the injection.
제제예Formulation example 5. 5. 액제의Liquid 제조 Produce
RS 20 mg
이성화당 10 g10 g of isomerized sugar
만니톨 5 g5 g of mannitol
정제수 적정량Purified Water Proper Amount
통상 액제의 제조방법에 따라 정제수에 각각의 성분을 가하여 용해시키고 레몬향을 적량 가한 다음 상기의 성분을 혼합한 다음 정제수를 가하여 전체를 정제수를 가하여 전체 100 ml로 조절한 후 갈색병에 충진하여 멸균시켜 액제를 제조한다.Normally, each component is added to the purified water to dissolve according to the preparation method of the liquid solution, lemon flavor is added, the above ingredients are mixed, purified water is added, the whole is adjusted to 100 ml by the addition of purified water, and then filled into a brown bottle and sterilized. To prepare a liquid solution.
제제예Formulation example 6. 건강기능식품의 제조 6. Preparation of dietary supplements
RS 1000 mg
비타민 혼합물 적량Vitamin mixture proper amount
비타민 A 아세테이트 70 ㎍70 μg of Vitamin A Acetate
비타민 E 1.0 mg Vitamin E 1.0 mg
비타민 B1 0.13 mgVitamin B1 0.13 mg
비타민 B2 0.15 mgVitamin B2 0.15 mg
비타민 B6 0.5 mgVitamin B6 0.5 mg
비타민 B12 0.2 ㎍0.2 μg of vitamin B12
비타민 C 10 mg
비오틴 10 ㎍10 μg biotin
니코틴산아미드 1.7 mgNicotinamide 1.7 mg
엽산 50 ㎍50 μg folic acid
판토텐산 칼슘 0.5 mgCalcium Pantothenate 0.5 mg
무기질 혼합물 적량Mineral mixture
황산제1철 1.75 mgFerrous Sulfate 1.75 mg
산화아연 0.82 mgZinc Oxide 0.82 mg
탄산마그네슘 25.3 mgMagnesium carbonate 25.3 mg
제1인산칼륨 15 mg15 mg potassium monophosphate
제2인산칼슘 55 mg
구연산칼륨 90 mgPotassium Citrate 90 mg
탄산칼슘 100 mg
염화마그네슘 24.8 mgMagnesium chloride 24.8 mg
상기의 비타민 및 미네랄 혼합물의 조성비는 비교적 건강기능식품에 적합한 성분을 바람직한 실시예로 혼합 조성하였지만, 그 배합비를 임의로 변형 실시하여도 무방하며, 통상의 건강기능식품 제조방법에 따라 상기의 성분을 혼합한 다음, 과립을 제조하고, 통상의 방법에 따라 건강기능식품 조성물 제조에 사용할 수 있다.Although the composition ratio of the above-mentioned vitamin and mineral mixtures is a composition that is relatively suitable for the health functional food, the composition is mixed in a preferred embodiment, but the compounding ratio may be arbitrarily modified, and the above ingredients are mixed according to a conventional health functional food manufacturing method. Then, the granules may be prepared and used for preparing the nutraceutical composition according to a conventional method.
제제예Formulation example 7. 건강 음료의 제조 7. Manufacture of health drinks
RS 1000 mg
구연산 1000 mg
올리고당 100 g100 g oligosaccharides
매실농축액 2 gPlum concentrate 2 g
타우린 1 g1 g of taurine
정제수 전체 900 ml900 ml of purified water whole
통상의 건강음료 제조방법에 따라 상기의 성분을 혼합한 다음, 약 1시간동안 85℃에서 교반 가열한 후, 만들어진 용액을 여과하여 멸균된 2 L 용기에 취득하여 밀봉 멸균한 뒤 냉장 보관한 다음 본 발명의 건강음료 조성물 제조에 사용한다.After mixing the above components according to the conventional healthy beverage production method, and stirred and heated at 85 ℃ for about 1 hour, the resulting solution is filtered and obtained in a sterilized 2 L container, sealed sterilization and then refrigerated and stored Used to prepare the healthy beverage composition of the invention.
상기 조성비는 비교적 기호음료에 적합한 성분을 바람직한 실시예로 혼합 조성하였지만, 수요계층, 수요국가, 사용용도 등 지역적, 민족적 기호도에 따라서 그 배합비를 임의로 변형 실시하여도 무방하다.Although the composition ratio is a mixture of the components suitable for the preferred beverage as a preferred embodiment, the blending ratio may be arbitrarily varied according to the regional and national preferences such as the demand level, the demanding country, and the intended use.
도 1은 실험기간동안 체중의 변화(A), 혈청 중 총 콜레스테롤 수치의 변화(B)를 보여주는 도이며,1 is a view showing the change in weight (A), the change in total cholesterol level in serum (B) during the experiment,
도 2는 혈청 중 중성지질 함량의 변화를 보여주는 도이고,Figure 2 is a diagram showing the change in the content of triglyceride in serum,
도 3은 혈청 중 LDL 함량의 변화를 보여주는 도이며,Figure 3 is a view showing the change in serum LDL content,
도 4는 혈청 중 HLD 함량의 변화를 보여주는 도이고,4 is a diagram showing a change in HLD content in serum,
도 5는 혈청 중 렙틴 함량의 변화를 보여주는 도이며,5 is a diagram showing the change in leptin content in serum,
도 6은 혈청 중 아디포넥틴 함량의 변화를 보여주는 도이고,6 is a diagram showing a change in adiponectin content in serum,
도 7은 난소주위 지방 세포의 평균 직경 변화를 보여주는 도이며,7 is a view showing the change in the average diameter of the ovarian fat cells,
도 8은 축적된 복벽 지방의 두께 변화를 보여주는 도이고, 8 is a view showing the thickness change of the accumulated abdominal wall fat,
도 9는 복벽 지방 세포 평균 직경 변화를 보여주는 도이며,9 is a diagram showing the change in the mean diameter of abdominal wall fat cells,
도 10은 정상사료 대조군(a), 고지방사료 공급 대조군(b) 및 메트포민 투여군(c)의 난소 주위 지방의 조직학적 변화를 보여주는 도이고,10 is a diagram showing the histological changes of the ovarian fat of the normal feed control (a), high fat feed supply control (b) and metformin administration group (c),
도 11은 RS 500(a), 250(b), 125 mg/kg 투여군(c)의 난소 주위 지방의 조직학적 변화를 보여주는 도이며,11 is a diagram showing the histological changes of the ovarian fat in the RS 500 (a), 250 (b), 125 mg / kg administration group (c),
도 12은 정상사료 대조군(a), 고지방사료 공급 대조군(b) 및 메트포민 투여군(c)의 복벽지방의 조직학적 변화를 보여주는 도이고,12 is a diagram showing the histological changes of abdominal wall fat of the normal feed control (a), high fat feed supply control (b) and metformin administration group (c),
도 13는 RS 500(a), 250(b), 125 mg/kg 투여군(c)의 복벽지방의 조직학적 변화를 보여주는 도이다.Figure 13 shows the histological changes of abdominal wall fat in RS 500 (a), 250 (b), 125 mg / kg administration group (c).
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