KR20140045791A - Composition for improving triglyceride containing poly-gamma-glutamic acid - Google Patents
Composition for improving triglyceride containing poly-gamma-glutamic acid Download PDFInfo
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- KR20140045791A KR20140045791A KR1020120111980A KR20120111980A KR20140045791A KR 20140045791 A KR20140045791 A KR 20140045791A KR 1020120111980 A KR1020120111980 A KR 1020120111980A KR 20120111980 A KR20120111980 A KR 20120111980A KR 20140045791 A KR20140045791 A KR 20140045791A
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- glutamic acid
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- A—HUMAN NECESSITIES
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/74—Synthetic polymeric materials
- A61K31/765—Polymers containing oxygen
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
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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
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
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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
- A23V2200/3262—Foods, ingredients or supplements having a functional effect on health having an effect on blood cholesterol
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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
- A23V2250/00—Food ingredients
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- A23V2250/0618—Glutamic acid
Abstract
Description
본 발명은 분자량 100Da~5,000kDa의 폴리감마글루탐산을 유효성분으로 함유하는 혈중 중성지방 개선용 조성물에 관한 것으로, 더욱 자세하게는 지방세포에서의 지방생성을 억제시키고, glucose-6- phosphate dehydrogenase 활성 및 지방분화 관련 전사인자 발현을 감소시켜 혈중 중성지방 수치를 개선시키는 분자량 100Da~5,000kDa의 폴리감마글루탐산을 유효성분으로 함유하는 중성지방 개선용 조성물에 관한 것이다.
The present invention relates to a composition for improving triglycerides in blood containing polygamma glutamic acid having a molecular weight of 100 Da to 5,000 kDa as an active ingredient, and more particularly, to inhibit fat formation in adipocytes, glucose-6-phosphate dehydrogenase activity and fat. The present invention relates to a composition for improving triglycerides containing polygamma glutamic acid having a molecular weight of 100 Da to 5,000 kDa as an active ingredient to reduce differentiation-related transcription factor expression to improve blood triglyceride levels.
중성지방은 우리 몸속에 존재하는 지질의 한 종류로 트리글리세라이드라고도 한다. 지방조직에 가장 많이 들어 있는 것이 중성지방이다. 중성지방의 가장 큰 역할은 체내 활동의 에너지원이 되는 것이며, 에너지를 저장하는 성질 때문에 저장지방이라고도 불리며 유리지방산도 이 부류이다. 콜레스테롤이나 인지질 등도 지질이지만 중성지방처럼 에너지가 되지 않고 세포막처럼 몸의 구조를 이루는 재료가 되어 구조지질이라고 불린다. 중성지방은 근육 등에서 에너지로 사용되는데 남은 분량은 지방조직 속 지방세포에 저장되며 이 저장량이 일정량 이상 증가한 상태가 비만이다. Triglycerides are a type of lipid that exists in our bodies, also called triglycerides. Neutral fat is the most abundant in adipose tissue. Triglycerides play a major role in energy activity in the body, and because of their energy-saving properties, they are also called storage fats, and free fatty acids are also in this class. Although cholesterol and phospholipids are lipids, they are called structural lipids because they do not become energy like triglycerides and become materials that form the body's structure like cell membranes. Triglycerides are used for energy in muscles, etc. The remaining amount is stored in fat cells in adipose tissue, and the amount of this increase is over a certain amount.
음식물에서 섭취한 중성지방은 소장에서 쓸개즙이라는 소화액과 췌장액에 들어 있는 지방분해효소에 의해 흡수되기 쉬운 작은 형태(유리지방산과 글리세롤)로 분해된다. 흡수된 후에는 중성지방으로 합성되어 혈액을 타고 몸 전체에 운반된다. 음식으로 섭취된 혈액 속의 포도당은 대부분 중성지방처럼 에너지로 사용되지만 남는 것은 간으로 운반된다. 중성지방의 재생 공장인 간은 운반되어온 포도당과 지방세포에서 방출된 유리지방산을 합성해 새로운 중성지방을 만들어낸다.Triglycerides taken from food are broken down into small forms (free fatty acids and glycerol) that are easily absorbed by the digestive enzymes called bile juice and lipolytic enzymes in pancreatic juice. After it is absorbed, it is synthesized into triglycerides, which are carried in blood and carried throughout the body. Most of the glucose in the blood taken from food is used for energy, like triglycerides, but what is left is carried to the liver. The liver, a triglyceride regeneration plant, synthesizes free fatty acids from glucose and fat cells that have been transported to produce new triglycerides.
지방세포는 중성지방을 축적하는 역할 외에도 호르몬과 비슷한 물질을 분비하는 역할을 한다. 지방세포가 분비하는 물질인 아디포사이토카인은 대사가 활발하게 이루어지는 내장지방의 지방세포에서 더 많이 분비하게 되며 지방세포가 비대해지면 해로운 아디포사이토카인 분비량이 증가하게 되어 동맥경화나 고혈압, 당뇨병 등이 생길 위험이 높아진다.In addition to accumulating triglycerides, fat cells also secrete hormone-like substances. Adipocytokine, a substance secreted by fat cells, is secreted more by fat cells of visceral fat, which are actively metabolized, and when fat cells become enlarged, harmful adipocytokine secretion increases, which leads to arteriosclerosis, high blood pressure, diabetes, etc. The risk of this is increased.
중성지방은 1g당 9kcal의 에너지를 내는데 중성지방 자체로는 에너지로의 기능을 하지 못하고 유리지방산이라는 지질로 분해되어야 한다. 리파아제는 지방세포와 혈액 속에 있는 중성지방을 유리지방산과 글리세롤로 분해하고 유리지방산은 혈액 속에서 근육으로 운반되어 연소된다. 에너지로 사용되지 못한 유리지방산은 혈액 속을 흐르다 간에 흡수된다. 필요 이상으로 분해되고 남은 유리지방산은 지방세포안에서 중성지방으로 합성되어 지방세포에 축적되는데 너무 많이 쌓이면 지방세포가 비대해지며 배출되는 유리지방산의 양도 증가하게 된다. 유리지방산이 혈액 속에 많으면 포도당과 합성되는 양도 많아져 중성지방이 점점 증가하게 된다. 이런 식으로 중성지방과 내장지방의 악순환이 계속되는 것이다.Neutral fat produces 9kcal of energy per gram. Neutral fat itself does not function as an energy and must be broken down into a lipid called free fatty acid. Lipase breaks down fat cells and triglycerides in the blood into free fatty acids and glycerol, which are transported to the muscles in the blood and burned. Free fatty acids, which are not used as energy, are absorbed through the blood. The remaining free fatty acid, which is decomposed more than necessary, is synthesized into triglycerides in the fat cells and accumulated in the fat cells, and when accumulated too much, the fat cells are enlarged and the amount of free fatty acids released is increased. If the free fatty acid is high in the blood, the amount synthesized with glucose increases, and the triglyceride increases gradually. In this way, the vicious cycle of triglycerides and visceral fat continues.
대사증후군은 내장지방형 비만을 중심으로 몇가지 위험 인자가 모인 상태를 가리키는 새로운 질환으로써 그 위험 인자는 내장지방형 비만, 고지혈증, 고혈압, 고혈당의 네 가지이다. 이러한 위험인자 중에서 내장지방형 비만을 포함하여 세가지 이상의 위험 인자가 있으면 대사증후군으로 진단된다. 대사증후군의 위험 인자를 가진 사람은 위험 인자가 없는 사람보다 협심증이나 심근경색 등 심장병에 걸릴 위험이 크다.Metabolic syndrome is a new disease that refers to a state where several risk factors have been gathered around visceral fat type obesity. The risk factors are four types: visceral fat type obesity, hyperlipidemia, hypertension and hyperglycemia. Among these risk factors, metabolic syndrome is diagnosed if there are three or more risk factors including visceral fat type obesity. People with risk factors for metabolic syndrome are more at risk for heart disease, such as angina or myocardial infarction, than those without risk factors.
중성지방의 치료를 위해서는 운동과 식이 조절이 가장 중요하며, 식단은 저열량 식이로 지방이 많이 포함된 음식을 줄여야 한다. 단순히 기름진 것을 적게 먹는다의 개념이 아니라, 탄수화물까지를 포함해서 적게 먹는 것이 필요하다. 몸무게가 많은 경우 체중감량 만으로도 중성지방 수치 및 각종 당뇨나 각종 심혈관계합병증의 위험을 줄일 수 있게 된다. 약물적인 방법으로는 fibrate제제(gemfibrozil, fenofibrate)를 사용할 수 있다. 이 약품은 중성지방 수치를 35-50% 정도 수치를 낮출 수 있는 것으로 알려져 있으나 타 약품을 복용시에 근육병증의 위험성이 증가하는 것으로 알려져 있다. 다른 약물로는 statins, nicotinic acid, 고용량의 오메가3지방산이 효과가 있으며, 중성지방을 낮추기 위해서 statin을 복용하는 경우는 LDL을 낮추기 위해서 복용하는 것보다 더 고용량을 사용해야 하는 단점이 있으며, 고용량의 오메가 3지방산을 복용하는 것도 ~40%정도 중성지방을 낮출수 있는것으로 알려져 있다. For the treatment of triglycerides, exercise and diet control are the most important, and the diet should be a low-calorie diet to reduce foods that contain a lot of fat. It's not just the idea of eating less oily things, but eating less carbs, including carbohydrates. If you are a lot of weight, weight loss alone will reduce your risk of triglyceride levels and various diabetes and cardiovascular complications. As a pharmacological method, fibrate preparations (gemfibrozil, fenofibrate) can be used. It is known to lower triglyceride levels by 35-50%, but the risk of myopathy increases when taking other medications. Other drugs include statins, nicotinic acid, and high doses of omega-3 fatty acids.If you take statins to lower triglycerides, you may need to use higher doses than to lower LDL. Taking trifatty acid is known to lower triglycerides by ~ 40%.
폴리감마글루탐산(γ-PGA)은 미생물에 의해 생산되는 점액성 물질이다. 폴리감마글루탐산은 볏짚을 이용한 한국의 전통 콩 발효식품인 청국장, 일본의 전통 콩 발효식품인 낫또, 네팔의 전통 콩 발효식품인 키네마 등에서 분리된 바실러스 속 균주로부터 생산된다. 바실러스 속 균주로부터 생산되는 폴리감마글루탐산은 식용, 수용성, 음이온성 및 생분해성 고분자물질로 흡습제, 보습제 및 화장품의 원료물질로 이용이 가능하다.Polygamma glutamic acid ([gamma] -PGA) is a mucous substance produced by microorganisms. Polygamma glutamic acid is produced from strains of the genus Bacillus isolated from Korean traditional soybean fermented food Cheonggukjang, Japanese traditional soybean fermented food natto, and Nepalese traditional soybean fermented food kinema. Polygamma glutamic acid produced from Bacillus strains is an edible, water-soluble, anionic and biodegradable polymer that can be used as a raw material for humectants, moisturizers and cosmetics.
본 발명자들은 고분자량 폴리감마글루탐산 및 그 이용방법에 대한 물질특허(대한민국 등록특허 제399091호), 고분자량의 폴리감마글루탐산을 생산하는 내염성 균주 바실러스 서브틸리스 청국장 균주를 사용하여 폴리감마글루탐산을 생산하는 방법에 관한 특허(대한민국 등록특허 제500796호)를 획득하였으며, 그 외에 폴리감마글루탐산을 함유하는 항암조성물, 면역보강제, 면역증강제 및 바이러스 감염 억제에 대한 특허(대한민국 등록특허 제496606호, 대한민국 등록특허 제517114호 및 대한민국 등록특허 제475406호, 대한민국 등록특허 제0873179호)를 획득한 바 있다. 또한, 폴리감마글루탐산의 면역증강을 통한 항암기능을 밝힘으로써 [Poo, H.R. et al ., Journal of Immunology, 178:775, 2007, Poo, H.R. et al., Cancer Immunol Immunother, 59:11, 2010], 폴리감마글루탐산의 의약 용도에 대한 연구가 진행되는 등, 폴리감마글루탐산에 대한 지속적인 용도 개발을 수행하며 다양한 효능들을 연구하였다. The present inventors produce polygamma glutamic acid using a high-molecular weight polygamma glutamic acid and a material patent for the method of using the same (Korean Patent No. 399091), a salt-tolerant strain Bacillus subtilis Chungkukjang strain producing high molecular weight poly gamma glutamic acid. Acquired a patent for a method (Korean Patent No. 500796), and a patent for anti-cancer composition containing polygamma glutamic acid, an immunoadjuvant, an immune enhancer, and a virus infection inhibition (Korean Patent No. 496606, Republic of Korea) Patent No. 517114, Republic of Korea Patent No. 475406, Republic of Korea Patent No. 0873179). In addition, by revealing the anti-cancer function through the immuno-enhancing polygamma glutamic acid [Poo, HR et al . , Journal of Immunology , 178: 775, 2007, Poo, HR et al ., Cancer Immunol Immunother , 59:11, 2010], and research on the medical use of polygamma glutamic acid, such as the ongoing development of polygamma glutamic acid has been carried out to study a variety of efficacy.
이에, 본 발명자들은 폴리감마글루탐산의 중성지방 개선에 대한 효과를 확인하고자 예의 노력한 결과, 분자량 100Da~5,000kDa의 폴리감마글루탐산이 고분자량의 폴리감마글루탐산보다 효과적으로 지방세포에서의 지방생성을 억제시키고 지방세포에서 활성이 증가되는 glucose-6-phosphate dehydrogenase 활성을 억제하고 지방분화 관련 전사인자 발현을 감소시킴으로써 중성지방 수치를 개선시키는 것을 확인하고, 분자량 100Da~5,000kDa의 폴리감마글루탐산이 중성지방에 의한 대사성질환을 예방 또는 치료할 수 있다는 것을 확인하고, 본 발명을 완성하게 되었다.
Accordingly, the present inventors have made diligent efforts to confirm the effect of polygamma glutamic acid on triglyceride improvement. As a result, polygamma glutamic acid having a molecular weight of 100 Da to 5,000 kDa inhibits the formation of fat in adipocytes more effectively than the high molecular weight poly gamma glutamic acid, Inhibition of glucose-6-phosphate dehydrogenase activity, which is increased in the cell, and improvement of triglyceride levels by decreasing the expression of transcription factors related to the differentiation, and polygamma glutamic acid with a molecular weight of 100 Da to 5,000 kDa was metabolized by triglyceride. It was confirmed that the disease can be prevented or treated, and the present invention has been completed.
본 발명의 주된 목적은 혈중 중성지방 개선에 대한 효과가 있는 폴리감마글루탐산 또는 그의 염을 유효성분으로 함유하는 혈중 중성지방 개선용 약학조성물을 제공하는 데 있다.
It is a main object of the present invention to provide a pharmaceutical composition for improving triglyceride in blood containing polygamma glutamic acid or a salt thereof having an effect on improving triglyceride in blood as an active ingredient.
상기 목적을 달성하기 위하여, 본 발명은 폴리감마글루탐산 또는 그의 염을 유효성분으로 함유하는 혈중 중성지방 개선용 약학조성물 및 건강기능식품을 제공한다.
In order to achieve the above object, the present invention provides a pharmaceutical composition for improving triglyceride in blood and health functional food containing polygamma glutamic acid or a salt thereof as an active ingredient.
본 발명에 따른 폴리감마글루탐산 함유 조성물은 혈중 중성지방 및 지방세포의 크기를 감소시키고, 독성 및 부작용이 거의 없어 예방 목적으로 장기복용이 가능하여, 중성지방 개선용 식음료로 섭취시 내장비만 및 동맥경화 등을 미리 예방하거나 개선할 수 있어 비만질환 및 혈관질환에 대한 치료 및 예방에 유용하다.
The polygamma glutamic acid-containing composition according to the present invention reduces the size of triglycerides and fat cells in the blood, and can be used for a long time for the purpose of prevention because there is almost no toxicity and side effects. It is useful for the treatment and prevention of obesity diseases and vascular diseases because it can be prevented or improved in advance.
도 1은 폴리감마글루탐산의 지방생성 억제 효능을 나타낸 것이다.
도 2는 폴리감마글루탐산에 의한 지방세포 내 포도당-6-인산탈수소효소 활성 억제 효능을 나타낸 것이다.
도 3은 폴리감마글루탐산에 의한 PPARγ와 C/EBPα의 mRNA 발현 감소를 나타낸 것이다.
도 4는 폴리감마글루탐산에 의한 SREBP1c의 발현 감소를 나타낸 것이다.
도 5는 폴리감마글루탐산에 의한 leptin과 fatty acid synthase의 mRNA 발현 감소를 나타낸 것이다.
도 6은 고중성지방혈증을 유도시킨 동물모델에서의 폴리감마글루탐산의 혈중 중성지방 감소 효능을 나타낸 것이다.
도 7은 고중성지방혈증을 유도시킨 동물모델에서의 간내 포도당-6-인산탈수소효소 활성 억제 효능을 나타낸 것이다.Figure 1 shows the lipogenesis inhibitory effect of polygammaglutamic acid.
Figure 2 shows the effect of inhibiting glucose-6-phosphate dehydrogenase activity in adipocytes by polygamma glutamic acid.
Figure 3 shows a decrease in mRNA expression of PPARγ and C / EBPa by polygamma glutamic acid.
4 shows a decrease in the expression of SREBP1c by polygammaglutamic acid.
Figure 5 shows the mRNA expression of leptin and fatty acid synthase by polygamma glutamic acid.
Figure 6 shows the effect of reducing triglycerides in blood of polygamma glutamic acid in animal models inducing hypertriglyceridemia.
Figure 7 shows the inhibitory effect of hepatic glucose-6-phosphate dehydrogenase activity in animal models inducing hypertriglyceridemia.
본 발명은 분자량 100Da~5,000kDa의 폴리감마글루탐산 또는 그의 염을 유효성분으로 함유하는 혈중 중성지방 개선용 약학조성물 및 건강기능식품에 관한 것이다.The present invention relates to a pharmaceutical composition for improving triglyceride in blood and health functional food containing polygamma glutamic acid having a molecular weight of 100 Da to 5,000 kDa or a salt thereof as an active ingredient.
본 발명에 있어서, 상기 염은 나트륨염, 칼륨염, 칼슘염, 마그네슘염, 암모늄염 및 아연염으로 구성된 군에서 선택되는 것임을 특징으로 할 수 있다.In the present invention, the salt may be selected from the group consisting of sodium salt, potassium salt, calcium salt, magnesium salt, ammonium salt and zinc salt.
본 발명에 있어서, 분자량 100Da 이하의 폴리감마글루탐산을 사용할 경우, 중성지방저해 효과를 기대할 수 없으며, 분자량 5,000kDa 이상의 폴리감마글루탐산을 사용할 경우, 중성지방 저해능이 현저히 감소하였다.In the present invention, when polygamma glutamic acid having a molecular weight of 100 Da or less is not expected, triglyceride inhibitory effect cannot be expected. When polygamma glutamic acid having a molecular weight of 5,000 kDa or more is used, triglyceride inhibitory ability is remarkably reduced.
본 발명의 일 양태에서는 바실러스 서브틸리스 청국장 균주가 생산하는 폴리감마글루탐산을 사용하였으며, 폴리감마글루탐산 나트륨염, 폴리감마글루탐산 칼슘염 및 폴리감마글루탐산 암모늄염을 사용하였다.In one embodiment of the present invention, polygamma glutamic acid produced by Bacillus subtilis Chungkukjang strain was used, and polygamma glutamate sodium salt, polygamma glutamate calcium salt, and polygamma glutamic acid ammonium salt were used.
본 발명의 약학조성물은 폴리감마글루탐산 또는 그의 염을 유효성분으로 함유하고 있으며, 폴리감마글루탐산은 이미 식품 및 화장품 계통에서 주요성분으로 구성되어 제조되고 시판되어 널리 이용되고 있는 것으로 알려져 있다.The pharmaceutical composition of the present invention contains polygamma glutamic acid or a salt thereof as an active ingredient, and polygamma glutamic acid is already known to be manufactured and marketed and widely used as a main component in food and cosmetic systems.
본 발명의 일양태에서는 폴리감마글루탐산을 처리한 지방세포에서 지방구 생성 효과를 확인하였을때, 1kDa의 폴리감마글루탐산을 처리하였을때 500kDa의 폴리감마굴르탐산 보다 지방축적 저해율이 우수하다는 것을 확인하였으며, GPDH(glcerol -3-phosphate dehydrogenase) 활성을 측정하였을 때, 1kDa의 저분자 폴리감마글루탐산을 처리하였을때 GPDH 활성이 500kDa 폴리감마글루탐산을 처리하였을 때 보다 현저히 저해되는 것을 확인하였다. In one embodiment of the present invention, when the adipocyte-producing effect of the poly-gamma glutamic acid was confirmed, when the 1-kDa poly-gamma glutamic acid was treated, it was confirmed that the fat accumulation inhibition rate was better than that of the poly-gammagultam acid of 500 kDa, When measuring glycerol-3-phosphate dehydrogenase (GPDH) activity, it was confirmed that the GPDH activity was significantly inhibited when treated with 1 kDa low molecular weight polygamma glutamic acid than when treated with 500 kDa polygamma glutamic acid.
또한, 지방분화 관련 전사인자 발현에 있어서도, 1kDa 폴리감마글루탐산을 처리한 지방전구세포에서 지방분화지표인 PPARγ와 C/EBPα의 발현이 500kDa 폴리감마글루탐산을 처리한 지방전구세포보다 훨씬 더 저해되는 것을 확인하였다. In addition, in the expression of adipose differentiation-related transcription factors, the expression of adipose differentiation index PPARγ and C / EBPa in adipocytes treated with 1 kDa polygamma glutamic acid was much more inhibited than adipocytes treated with 500 kDa polygamma glutamic acid. Confirmed.
본 발명의 다른 양태에서는 생리적 섭취 수준 즉, 일상적 섭취 수준에서 γPGA의 중성지방 개선 효과를 확인하기 위하여, 동물에 고지방 식이를 이용하여 비만, 고지혈증을 유발한 후 γPGA 및 염 형태의 γPGA를 식이 무게의 0.1% 수준(0.2g/㎏ 몸무게) 수준에서 섭취케 한 후 체중증가, 식이 섭취량, 체내 지질대사, 혈당, 지방세포 조직학적 형태 및 지방합성 효소 유전자 발현에 미치는 영향을 분석한 결과, 정상체중군에서는 γPGA나 염 형태의 γPGA 섭취시 체중증가에는 영향을 주지 않았고, 고지방식이군에서 0.1% γPGA 첨가시 체중 증가를 유의적으로 억제하였으며, 염의 형태가 아닌 γPGA에서 가장 체중 증가량이 적었다. In another embodiment of the present invention, in order to confirm the triglyceride-improving effect of γPGA at the physiological intake level, that is, the daily intake level, γPGA and salt form γPGA in the form of γPGA and salt form γPGA after inducing obesity and hyperlipidemia in animals. After ingestion at the 0.1% level (0.2 g / kg body weight), the effects on body weight gain, dietary intake, lipid metabolism, blood glucose, adipocyte histologic morphology, and fat synthase gene expression were analyzed. Did not affect body weight gain intake of γPGA or γPGA in salt form. In the high-fat diet, 0.1% γPGA addition significantly inhibited weight gain, and the least amount of γPGA was found in non-salt form.
실험동물의 간, 신장주변 지방과 부고환 지방의 무게를 측정한 결과, 간과 부고환의 지방 무게, 신장주변 지방무게는 10% 지방식이를 섭취하였던 저지방식이군이 45% 지방을 섭취하였던 고지방식이군에 비해 유의하게 낮게 나타났고, 비만 유도시 간, 부고환 지방의 무게는 γPGA 섭취에 의한 영향이 나타나지 않았다. 그러나 내장지방인 신장주변의 지방은 γPGA 섭취로 인해 유의하게 낮아졌으며 γPGA 섭취시 염 형태의 γPGA 섭취에 비해 가장 낮아서, γPGA 섭취는 내장지방의 발달을 억제하는 효과가 있는 것으로 나타났다. 신장주변의 지방세포의 형태학적 발달은 정상체중군에 비해 비만 유발군의 지방세포의 크기가 컸으며, γPGA 섭취로 인해 지방세포의 크기가 작아졌으며 이는 정상체중군이나 비만 유발군에서 모두 γPGA 섭취의 영향이 있었다. 지방세포의 크기는 정상체중군에 비해 비만 유발군에서 지방세포의 크기가 유의하게 커졌으며, γPGA 섭취로 인해 정상체중군이나 비만 유발군에서 지방세포가 작아졌으며 염 형태의 γPGA에 의한 차이는 없었고, γPGA는 내장지방의 발달을 억제하는 것을 알 수 있었다.The weights of liver, epididymal and epididymal fats of experimental animals were measured, and the low-fat diets that consumed 10% fat for the liver and epididymis fat weight and peri-digestive fat were fed high fat diets that consumed 45% fat. It was significantly lower than that of obesity, and the weight of epididymal fat was not affected by γPGA intake. However, the fat around the kidney, which is visceral fat, was significantly lowered due to the intake of γPGA and was the lowest compared to the intake of γPGA in the form of salt when ingesting γPGA. Therefore, the intake of γPGA has the effect of inhibiting the development of visceral fat. The morphological development of adipocytes around the kidney was larger in obesity-induced adipocytes than in normal-weight group and decreased in size by γPGA ingestion. There was an influence. The size of adipocytes was significantly increased in obesity-induced group compared with normal-weight group, and adipocytes became smaller in normal-weight or obesity-induced group due to γPGA intake. , γPGA was found to inhibit the development of visceral fat.
본 발명의 다른 실시예에서, 혈장 내 중성지방 농도는 저지방식이군에 비해 고지방식이군이 낮았으나 총 콜레스테롤과 LDL-콜레스테롤은 유의하게 높았으며, HDL-콜레스테롤은 유의하게 낮아졌다. 정상체중군인 저지방식이군에서 γPGA 섭취시 혈중 중성지방을 감소시켰으며 칼슘염 형태의 γPGA 섭취군에서 가장 혈중 중성지방을 감소시켰다. 혈중 총 콜레스테롤 농도도 정상체중군에서 γPGA 섭취에 의해 감소하였으며 칼슘염 형태의 γPGA 섭취군에서 가장 낮았다. 고지방식으로 비만을 유도시 HDL 콜레스테롤이 감소하나 γPGA는 HDL 콜레스테롤을 상승시키는 효과가 있었으며 γPGA 섭취군에서 가장 높았다. 혈중 LDL 콜레스테롤은 비만 유도군에서 높았으나 모두 정상범위였고, γPGA 섭취에 의한 효과는 없었다. In another embodiment of the present invention, plasma triglyceride concentration was lower in the high fat diet group than in the low-fat diet group, but total cholesterol and LDL-cholesterol were significantly higher, and HDL-cholesterol was significantly lower. In the low-weight group, the normal weight group, γPGA intake decreased blood triglycerides, and calcium salt-type γPGA intake group reduced the blood triglyceride most. Serum total cholesterol was also decreased by γPGA intake in the normal weight group and the lowest in the γPGA intake group in the form of calcium salt. Induction of obesity by high fat diet reduced HDL cholesterol, but γPGA had the effect of elevating HDL cholesterol and was the highest in the γPGA intake group. Serum LDL cholesterol was higher in the obesity induction group, but all of them were in the normal range, and there was no effect of γPGA intake.
간 조직 내의 총 지방과 콜레스테롤함량은 비만 유발군에서 유의하게 증가하였다. γPGA 섭취시 정상 체중군에서 총 지방과 콜레스테롤 축적을 억제하였으며, γPGA보다 염 형태의 γPGA에서 그 효과가 더 높았다. 비만 유발군에서 염형태의 γPGA의 섭취는 총 지방과 콜레스테롤 축적을 억제하는 경향이었으나 유의적이지는 않았다.Total fat and cholesterol content in liver tissue were significantly increased in the obese group. Intake of γPGA inhibited the accumulation of total fat and cholesterol in the normal weight group, and the effect was higher in the salt form of γPGA than in γPGA. Intake of γPGA in the salt form in the obese group tended to inhibit total fat and cholesterol accumulation but was not significant.
포도당-6-인산탈수소효소(glucose-6-phosphate dehydrogenase)의 mRNA를 실시간 RT-PCR로 측정한 것은 도 2와 같으며, γPGA의 섭취시 포도당-6-인산탈수소효소 유전자의 발현을 유의하게 억제하였으며 칼슘염 형태의 γPGA 섭취군에서 가장 유전자 발현이 낮았다. γPGA 섭취의 효과는 정상체중군과 비만 유발군 모두에서 유의하여 γPGA 섭취시 지방합성을 유의하게 억제하는 효과가 있음을 알 수 있었으며, 이로 인해 간 내 지방 축적, 지방세포 크기를 감소시킬 수 있는 것으로 판단된다.The measurement of glucose-6-phosphate dehydrogenase mRNA by real-time RT-PCR is shown in FIG. 2, and significantly inhibited the expression of the glucose-6-phosphate dehydrogenase gene upon ingestion of γPGA. The gene expression was lowest in the calcium salt type γPGA intake group. The effect of γPGA intake was significant in both the normal weight group and the obesity-induced group, and it was found that the effect of γPGA significantly inhibited the synthesis of fat, thereby reducing the accumulation of fat and the size of fat cells in the liver. Judging.
본 발명의 또 다른 양태에서는 기존 전임상 및 인체시험 자료 분석을 통하여, 1차적으로 확인한 폴리감마글루탐산의 콜레스테롤 개선 기능성을 인체에서 확인하기 위해 인체시험을 실시한 결과, 피험자 각 실험군과 대조군의 나이 및 임상시험 평균 복용률은 통계적으로 유의한 차이가 없었으며, 8주 후 혈압 및 맥박의 각 군간의 변화에서 통계적으로 유의한 차이가 나타나지 않았다. 8주 후 체중 및 신체계측 변화를 살펴보면 각 군간 비교에서 통계적으로 유의한 차이가 나타나는 변수는 없었으나, 대조군에 비해 0.15g 섭취군에서는 체질량지수가 대조군과 비교하여 감소하는 경향을 보였으며, 혈중 중성지방 수치는 유의적으로 감소한 것으로 나타났다.In another embodiment of the present invention, through the analysis of existing preclinical and human test data, the human body test to confirm the cholesterol-improving functionality of the polygamma glutamic acid first confirmed in the human body, the age and clinical trials of each test subject and control group There was no statistically significant difference in mean dose and there was no statistically significant difference in blood pressure and pulse rate change after 8 weeks. After 8 weeks, there was no statistically significant difference in the comparison of body weight and body measurement. However, the body mass index tended to decrease in the 0.15g group compared to the control group. Fat levels were significantly reduced.
본 발명에 따른 중성지방 개선용 약학조성물의 인체에 대한 투여량은 환자의 나이, 몸무게, 성별, 투여형태, 건강상태, 투여경로 및 질환 정도에 따라 달라질 수 있다. 그러나 바람직한 효과를 위하여, 1회 투여량은 0.1~10 g/㎏이 바람직하며, 상기 투여량은 어떠한 면으로든 본 발명의 범위를 한정하는 것은 아니다. 또한, 연령, 성별, 체중 및 건강상태에 따라 증감될 수 있다.The dosage of the triglyceride-improving pharmaceutical composition according to the present invention to a human body may vary depending on the age, weight, sex, dosage form, health condition, route of administration, and degree of disease of the patient. However, for the desired effect, the single dose is preferably 0.1-10 g / kg, and the dose does not limit the scope of the present invention in any aspect. It may also increase or decrease depending on age, sex, weight and health condition.
본 발명의 중성지방 개선용 약학조성물은 혈중 중성지방 개선을 목적으로 건강기능식품에 첨가될 수 있다. 본 발명의 중성지방 개선용 약학조성물은 건강기능식품 1일 섭취량에 대하여, 0.05 g~2 g이 바람직하며, 1일 섭취량 0.05 g 이하일 경우, 중성지방 개선 효과를 기대할 수 없으며, 2g 이상일 경우 함량증가에 따른 중성지방 개선 효과를 기대할 수 없을 뿐만 아니라 고비용을 초래하여, 경제적이지 못하다.
The pharmaceutical composition for improving triglyceride of the present invention may be added to a dietary supplement for the purpose of improving triglyceride in blood. The pharmaceutical composition for improving triglyceride of the present invention is preferably 0.05 g to 2 g with respect to the daily intake of the health functional food, and when the daily intake is 0.05 g or less, the triglyceride improvement effect cannot be expected, and the content increases if the concentration is greater than 2 g. Not only can not be expected to improve triglycerides due to the high cost, it is not economical.
이하, 실시예를 통하여 본 발명을 더욱 상세히 설명하고자 한다. 이들 실시에는 오로지 본 발명을 예시하기 위한 것으로, 본 발명이 범위가 이들 실시예에 의해 제한되는 것으로 해석되지 않는 것은 당업계에서 통상의 지식을 가진 자에게 있어서 자명할 것이다.
Hereinafter, the present invention will be described in more detail with reference to Examples. It is to be understood by those skilled in the art that these embodiments are merely illustrative of the present invention and that the present invention is not construed as being limited by these embodiments.
실시예Example 1: One: 고분자량High molecular weight 폴리감마글루탐산Polygamma Glutamic Acid 및 그 염의 제조 And preparation of salts thereof
폴리감마글루탐산 생산용 기본배지(3%의 L-글루탐산이 첨가된 배지; 글루코오스 3%, (NH4)2SO4 1%, KH2PO4 0.27%, Na2HPO4/12H2O 0.17%, NaCl 0.1%, 시트르산나트륨(Sodium citrate) 0.5%, Soypeptone 0.02%, MgSO4/7H2O 0.7%, 비타민용액(Vitamin solution) 10㎖/ℓ, pH 6.8)을 멸균시켜 준비하고, 5ℓ 발효기(Jar fermentor, working volume은 3ℓ)에 바실러스 서브틸리스 청국장 균주(Bacillus subtilis var chungkookjang, KCTC 0697BP)의 종균 배양액(LB 배지)을 4% 접종하여 발효시켰다. 교반속도는 500rpm, 공기주입속도는 1.0vvm으로 하여 37℃에서 48시간 동안 발효시킨 후 필터프레스(규조토 함유)를 사용하여 균체를 제거하여 폴리감마글루탐산 함유 시료 액을 수득하였다.Basic medium for the production of polygamma glutamic acid (medium with 3% L-glutamic acid; glucose 3%, (NH 4 ) 2 SO 4 1%, KH 2 PO 4 0.27%, Na 2 HPO 4 / 12H 2 O 0.17% , NaCl 0.1%, sodium citrate 0.5%, Soypeptone 0.02%, MgSO 4 / 7H 2 O 0.7%, vitamin solution (10ml / ℓ, pH 6.8) to sterilize, 5L fermenter ( Jar fermentor, working volume was fermented by inoculating 4% seed culture (LB medium) of Bacillus subtilis var chungkookjang (KCTC 0697BP) in 3L). The stirring speed was 500rpm, the air injection speed was 1.0vvm, and fermented at 37 ° C. for 48 hours to remove the cells using a filter press (containing diatomaceous earth) to obtain a polygamma glutamic acid-containing sample liquid.
폴리감마글루탐산 함유 시료액에 2N 황산용액을 이용하여 pH 2.0으로 조정한 후 10℃에서 15시간 동안 정치시켜 폴리감마글루탐산 침전물을 수득하였다. 수득한 폴리감마글루탐산 침전물을 충분한 양의 10℃ 이하의 냉각 증류수로 세척한 후(pH 3.5 이상), 누체여과기를 이용하여 폴리감마글루탐산 침전물을 수득 후 동결건조하여 고분자량 폴리감마글루탐산을 제조하였다.The polygamma glutamic acid-containing sample solution was adjusted to pH 2.0 using 2N sulfuric acid solution and then left at 10 ° C. for 15 hours to obtain a polygamma glutamic acid precipitate. The obtained polygamma glutamic acid precipitate was washed with a sufficient amount of cold distilled water of 10 ° C. or less (pH 3.5 or more), and then obtained polygamma glutamic acid precipitate using a Licech filter, followed by lyophilization to prepare a high molecular weight polygamma glutamic acid.
폴리감마글루탐산 염을 제조하기 위하여, 황산용액을 이용하여 침전시켜 얻은 폴리감마글루탐산 침전물에 식품첨가물 수산화나트륨을 첨가하여 중성의 pH로 용해시켜 얻은 폴리감마글루탐산 나트륨염 용액 및 폴리감마글루탐산 칼슘염 용액을 동결건조하고, 폴리감마글루탐산 나트륨염 및 폴리감마글루탐산 칼슘염 분말을 제조하였다. 또한 식품첨가물 중수산화마그네슘 첨가하여 중성의 pH로 용해시켜 얻은 폴리감마글루탐산 마그네슘염 용액을 동결건조하여 폴리감마글루탐산 마그네슘염 분말을 제조하였다. 또한 식품첨가물 중탄산암모늄을 첨가하여 중성의 pH로 용해시켜 얻은 폴리감마글루탐산 암모늄염 용액을 동결건조하여 폴리감마글루탐산 암모늄염 분말을 제조하였다.
In order to prepare polygamma glutamic acid salt, polygamma glutamate sodium salt solution and polygamma glutamate salt solution obtained by dissolving the polygamma glutamic acid precipitate obtained by precipitation with sulfuric acid solution to neutral pH by adding food additive sodium hydroxide Lyophilization and polygamma glutamate sodium salt and polygamma glutamate calcium salt powder were made. In addition, the polygamma glutamic acid magnesium salt powder was prepared by lyophilizing the polygamma glutamic acid magnesium salt solution obtained by adding magnesium hydroxide to food additives and dissolving it at neutral pH. In addition, the polygamma glutamic acid ammonium salt powder was prepared by freeze-drying the polygamma glutamic acid ammonium salt solution obtained by adding food additive ammonium bicarbonate to a neutral pH.
실시예Example 2: 지방세포를 이용한 2: using fat cells 폴리감마글루탐산의Of polygammaglutamic acid 중성지방 감소 기능 Triglyceride Reduction
2-1: 지방세포의 2-1: fat cell 지방구District ball 생성 저해 효과 Generation inhibitory effect
폴리감마글루탐산의 첨가가 지방생성 저해에 효과가 있는지를 측정하기 위하여 Oil-Red O staining을 실시하였다. Oil-Red O로 염색하게 되면 중성지방, cholesterol ester만이 염색되고, 그 외 유리지방산, 인지질은 염색이 되지 않는다. 지방의 축적된 부분은 대부분이 중성지방이기 때문에 Oil-Red O로 염색하여 지방축적 및 지방세포 분화 정도를 확인할 수 있다. 본 실험에서는 세포독성이 전혀 나타나지 않았던 1, 500, 2000 kDa 의 시료를 각각 0.5, 1 mg/mL의 농도로 처리하여 분화를 유도한 후 Oil-Red O 염색하여 위상차 현미경으로 관찰하였다. 폴리감마글루탐산을 처리하지 않고 분화를 유도하였을 경우에 세포질 내 lipid droplet의 형성이 활발하게 유발되는 것으로 관찰되었으나, 폴리감마글루탐산의 처리에 의하여 lipid droplet 형성이 1, 500, 2000 kDa 모두 농도 의존적으로 저해되는 것을 확인하였다. Oil-Red O staining was carried out to determine whether the addition of polygamma glutamic acid was effective in inhibiting lipogenesis. When stained with Oil-Red O, only triglycerides and cholesterol esters are dyed. Other free fatty acids and phospholipids are not dyed. Since most of the accumulated part of fat is triglyceride, staining with Oil-Red O can confirm fat accumulation and adipocyte differentiation. In this experiment, samples of 1, 500 and 2000 kDa, which showed no cytotoxicity, were treated at concentrations of 0.5 and 1 mg / mL, respectively, to induce differentiation, and then observed by phase contrast microscopy with Oil-Red O staining. It was observed that lipid droplet formation in the cytoplasm was actively induced when differentiation was induced without polygamma glutamic acid, but lipid droplet formation was inhibited in a concentration-dependent manner by treatment with polygamma glutamic acid. It confirmed that it became.
지방구에 염색된 Oil-Red O를 isopropanol로 용출시켜 흡광도를 측정한 결과 폴리감마글루탐산의 Ca 형태가 Na 형태에 비해 전체적으로 지방축적을 저해하는 효과를 나타내었다. 특히 폴리감마글루탐산 Ca 형태 1, 500 kDa를 1 mg/mL 처리한 시료에서는 대조구와 비교하여 각각 48%, 41%의 지방축적 저해율을 보여 가장 우수한 효과를 나타내었다.
Oil-Red O stained on fat globules was eluted with isopropanol, and the absorbance was measured. As a result, the Ca form of polygamma glutamic acid inhibited fat accumulation as a whole. In particular, the sample treated with 1 mg / mL of polygamma glutamic
2-2: 2-2: GlycerolGlycerol -6--6- phosphatephosphate dehydrogenasedehydrogenase 활성 저해 효과 Activity inhibitory effect
GPDH는 지방 및 근육세포에서 dihydroxyacetone phosphate를 glycero-6- phosphate로 전환함으로써 Triglyceride(TG) 생합성에 관여하는 효소 중의 하나이다. 따라서 폴리감마글루탐산에 의한 중성지방 생성 감소에 GPDH의 관여 여부를 알아보기 위해 Oil-Red O에서 우수한 효과를 나타낸 Ca 형태의 1, 500 kDa를 농도별로 처리하였다. 시료를 처리하지 않은 대조구에 비해 두 분자량 모두 GPDH 활성을 현저히 저해하였다. 특히 500 kDa의 고분자 보다 1 kDa의 저분자에서 GPDH 활성이 저해되는 것으로 나타났다. 따라서 지방 세포 내 중성지방 생성 저해는 폴리감마글루탐산에 의한 GPDH 활성 저해가 관여하는 것으로 확인되었다.
GPDH is one of the enzymes involved in triglyceride (TG) biosynthesis by converting dihydroxyacetone phosphate to glycero-6-phosphate in fat and muscle cells. Therefore, to determine whether GPDH is involved in the reduction of triglyceride production by polygamma glutamic acid, 1,500 kDa of Ca type, which showed excellent effect in Oil-Red O, was treated by concentration. Both molecular weights significantly inhibited GPDH activity as compared to the control without the sample. In particular, GPDH activity was inhibited at a low molecular weight of 1 kDa than the polymer of 500 kDa. Therefore, inhibition of triglyceride production in adipocytes was found to be involved in the inhibition of GPDH activity by polygammaglutamic acid.
2-3: 지방분화 관련 전사인자 발현에 미치는 영향2-3: Effect on the Expression of Adipose Differentiation-related Transcription Factors
지방전구세포에서 지방세포로 분화되는 adipogenesis 과정은 많은 종류의 adipogenic transcription factor들의 단계적인 조절에 의하여 유발되는 것으로 알려져 있다. 특히 이러한 adipogenic transcription factor들 중에서 C/EBP 및 PPAR family가 중요한 역할을 하는 것으로 보고되었다. 먼저 분화유도인자에 노출되면 몇 시간 이내에 C/EBPβ의 발현이 유발되면서 분화가 시작되며, C/EBPβ는 insulin-sensitive glucose uptake와 같은 성숙한 비만세포의 특징을 증가시키는 C/EBPα 및 PPARγ의 발현을 촉진하여 분화과정을 이룬다. 따라서 폴리감마글루탐산이 adipogenic transcription factor들의 발현에 미치는 효과를 분석하기 위하여, 앞선 실험에서 효과가 우수하였던 Ca 형태 폴리감마글루 탐산을 농도별로 처리하여 mRNA 발현 양상을 분석하였다. The process of adipogenesis that differentiates from adipocytes into adipocytes is known to be caused by the stepwise regulation of many types of adipogenic transcription factors. In particular, among these adipogenic transcription factors, the C / EBP and PPAR families play an important role. When exposed to differentiation-inducing factors, differentiation begins by inducing C / EBPβ expression within a few hours, and C / EBPβ is responsible for the expression of C / EBPa and PPARγ, which increase the characteristics of mature mast cells such as insulin-sensitive glucose uptake. Accelerate and differentiate. Therefore, in order to analyze the effect of polygamma glutamic acid on the expression of adipogenic transcription factors, mRNA expression patterns were analyzed by treating Ca-type polygammaglutamic acid, which was excellent in previous experiments, by concentration.
그 결과, 1 kDa의 저분자 폴리감마글루탐산을 농도별로 처리하면 PPARγ와 C/EBPα의 mRNA발현이 농도가 증가함에 따라 유의적으로 감소하는 것을 확인하였다. 특히, 1 mg/mL로 처리하였을 때 PPARγ와 C/EBPα의 mRNA발현이 각각 58%, 38% 감소하여, Oil-Red O 염색을 통한 세포관찰 결과와 일치하였다. 반면에, 500 kDa의 고분자 폴리감마글루탐산을 농도별로 처리하면 C/EBPα의 mRNA발현은 농도 의존적으로 감소하는 양상을 보였지만 PPARγ의 발현은 농도와 관계없이 약간 감소하였으나 대조구에 비해 발현차이가 크지 않았다. 또한 1 kDa와는 다르게 500 kDa에서만 PPARγ ligand 생성에 관여하는 전사인자인 SREBP1c의 발현이 농도 비의존적으로 저하됨을 확인하였다.As a result, it was confirmed that mRNA treatment of PPARγ and C / EBPa decreased significantly as the concentration was increased when the low molecular weight polygammaglutamic acid of 1 kDa was treated for each concentration. In particular, the mRNA expression of PPARγ and C / EBPa decreased by 58% and 38%, respectively, when treated at 1 mg / mL, consistent with the results of cell observation through Oil-Red O staining. On the other hand, when the poly-gamma glutamic acid of 500 kDa was treated by concentration, the mRNA expression of C / EBPa decreased in a dose dependent manner, but the expression of PPARγ was slightly decreased regardless of the concentration, but the expression difference was not large. In addition, unlike 1 kDa, it was confirmed that the expression of SREBP1c, which is a transcription factor involved in PPARγ ligand generation, decreased only in 500 kDa.
PPARγ는 지방대사를 조절하는 leptin 및 지방합성에 관여하는 fatty acid synthase(FAS)의 발현을 조절하는데, leptin은 지방세포에서 생성하고 혈관으로 분비되어 시상하부의 포만 중추를 자극하는 식욕조절인자로써 발열반응과 활동량을 증가시키고 체지방량을 감소시키는 생리적 작용을 가지고 있다고 보고되고 있다(Baile, Della-Fera & Martin, 2000). McDougald, Hwang, Fan & Lane (1995)에 따르면, 3T3-L1 지방세포는 분화과중 중 leptin을 생산하여 세포 중으로 분비하므로 세포 배양액에 증가된 leptin의 함량은 지방세포의 분화와 양의 상관관계를 갖는다고 보고하였다. 본 실험에서 500 kDa 처리구에서 농도 의존적으로 leptin mRNA 발현이 현저하게 감소하였는데, 1 mg/mL의 농도에서 약63%의 높은 저해율을 보였다. 또한 500 kDa 0.5, 1 mg/mL에서 FAS의 mRNA 발현이 대조구에 비교하여 유의적으로 감소하였다. PPARγ regulates the expression of leptin, which regulates fat metabolism, and fatty acid synthase (FAS), which is involved in fat synthesis.Leptin is an appetite regulator that stimulates the sagittal center of the hypothalamus, produced by adipocytes and secreted into blood vessels. It has been reported to have physiological effects that increase response and activity and decrease body fat mass (Baile, Della-Fera & Martin, 2000). According to McDougald, Hwang, Fan & Lane (1995), 3T3-L1 adipocytes produce and secrete leptin during differentiation, so the increased leptin content in cell culture correlates positively with the differentiation of adipocytes. Reported. In this experiment, the expression of leptin mRNA was significantly decreased in 500 kDa treatment, showing a high inhibition rate of about 63% at the concentration of 1 mg / mL. In addition, mRNA expression of FAS was significantly decreased at 500 kDa 0.5 and 1 mg / mL compared to the control.
고분자의 폴리감마글루탐산은 저분자에서 효과를 나타내었던 전사인자뿐만 아니라 그 외의 지방대사 관련 인자들의 mRNA 발현을 감소하였다. 이러한 전사인자들의 발현 양상은 다음의 지방세포 내 TG축적 결과와 일치하여, 폴리감마글루탐산에 의한 전사인자들의 발현 조절이 관여하는 것으로 확인되었다.
Polygamma-glutamic acid of the polymer reduced the mRNA expression of not only the transcription factor that was effective in the low molecule but also other fat metabolism related factors. The expression pattern of these transcription factors was confirmed to be involved in the regulation of expression of transcription factors by polygamma glutamic acid, consistent with the following TG accumulation results in adipocytes.
2-4: 중성지방 축적 저해 효과2-4: Triglyceride Accumulation Inhibitory Effect
3T3-L1 지방세포내 TG 축적에 미치는 영향을 알아보기 위하여 TG 함량을 측정한 결과 대조군에서 TG 함량은 158 nmol/mg protein으로 나타났다. Ca 형태 폴리감마글루탐산의 첨가 농도에 따른 TG 함량은 전체적으로 1 kDa보다 500 kDa가 낮았다. 특히, 500 kDa에서 0.5 mg/mL 농도는 81 nmol/mg protein과 1 mg/mL 농도는 95 nmol/mg protein 으로 대조구와 비교하여 세포내 중성지방의 축적을 유의적으로 저해하였다. 다만, 0.25 mg/mL에서의 지방축적은 분자량과 관계없이 전혀 효과가 없는 것으로 보아 농도 비의존적으로 TG 축적이 저해됨을 알 수 있었다.
To determine the effect on TG accumulation in 3T3-L1 adipocytes, the TG content was found to be 158 nmol / mg protein in the control group. The TG content of Ca-type polygammaglutamic acid was lower than 1 kDa as a whole. In particular, at 500 kDa, the concentration of 0.5 mg / mL was 81 nmol / mg protein and the concentration of 1 nm / mL was 95 nmol / mg protein, which significantly inhibited the accumulation of triglycerides in cells. However, fat accumulation at 0.25 mg / mL was found to have no effect regardless of molecular weight, indicating that TG accumulation was inhibited in a concentration-independent manner.
실시예Example 3: 3: 랫드Rat 모델에서의 In the model 폴리감마글루탐산의Of polygammaglutamic acid 중성지방 개선 기능 Triglyceride Improvement
생리적 섭취 수준 즉, 일상적 섭취 수준에서 γPGA의 중성지방 개선 효과를 확인하기 위하여, 동물에 고과당 식이를 이용하여 고중성지방혈증을 유발한 후 γPGA 및 염 형태의 γPGA를 식이 무게의 0.1% 수준(0.2g/㎏ 몸무게) 수준에서 섭취케 한 후 체중증가, 식이 섭취량, 체내 지질대사, 혈당, 지방세포 조직학적 형태 및 지방합성 효소 유전자 발현에 미치는 영향을 분석하였다.
To determine the triglyceride-improving effect of γPGA at physiological intake levels, that is, daily intake levels, hypertriglyceridemia was used in animals to induce hypertriglyceridemia, and then γPGA and salt form γPGA were added to 0.1% level of dietary weight ( 0.2g / kg body weight) and the effects on weight gain, dietary intake, lipid metabolism, blood glucose, adipocyte histologic morphology, and lipase gene expression were analyzed.
3-1: 실험동물의 사육 및 식이3-1: Breeding and Diet of Experimental Animals
본 발명에서 실험동물은 (주)중앙동물로부터 이유된 8주령의 Sprague-Dawley 수컷 쥐 40마리를 사용했다. 실험실 환경조건은 온도 22 ± 2 ℃, 상대 습도 65 ± 5 % 와 낮과 밤 주기는 12시간(오후 9시에 불이 켜짐)으로 하였으며, 각각 개별적인 금속 케이지에서 사육했다. 새로운 환경에 적응이 끝난 후, 실험동물은 대조군(NC) 10마리와 고과당섭취군(HC) 30마리로 무작위 실험군을 나누어 대조군은 정상식이를 4주간 공급하고, 고과당섭취군은 4주간의 고과당식(식이 무게의 63% 과당 함유)이 섭취로 고중성지방혈증으로 유도했다. 고과당섭취군의 유도확인을 마친 후 각 10마리씩 3그룹으로 무작위로 실험군을 나누어, 저농도 γ-PGA (150mg/kg bw)군과 고농도 γ-PGA (300mg/kg bw)군에게는 γ-PGA를 4주간 경구투여 하였다. 4주간의 실험식이 투여가 끝난 후, 혈청의 지질 대사 및 간의 지질 대사 분석을 하였다.
In the present invention, 40 rats of 8-week-old Sprague-Dawley male rats, which were weaned from a central animal, were used. Laboratory environmental conditions were temperature 22 ± 2 ° C, relative humidity 65 ± 5%, and day and night cycles for 12 hours (lighted up at 9 pm) and were housed in separate metal cages. After adaptation to the new environment, the experimental animals were divided into 10 control groups (NC) and 30 high fructose ingested groups (HC) and the control group fed a normal diet for 4 weeks, and the high fructose intake group for 4 weeks. High fructose diet (containing 63% of fructose weight) led to hypertriglyceridemia. After confirming the induction of the high fructose intake group, randomly divided the experimental groups into three groups of 10 animals each, and γ-PGA for the low concentration γ-PGA (150 mg / kg bw) group and the high concentration γ-PGA (300 mg / kg bw) group. Oral administration for 4 weeks. After 4 weeks of dietary administration, serum lipid metabolism and liver lipid metabolism analysis were performed.
3-2: 3-2: 혈장내Plasma 중성지방, 총콜레스테롤, Triglycerides, total cholesterol, HDLHDL -콜레스테롤 및 Cholesterol and LDLLDL -콜레스테롤-cholesterol
고과당식이 후 γPGA를 4주간 섭취시킨 실험군에서는 총콜레스테롤 및 LDL-콜레스테롤 수치가 유의적으로 감소하였으며, HDL-콜레스테롤은 증가한 것으로 나타났다. 고과당식이를 통한 고중성지방혈증 실험동물의 중성지방 수준이 평균 300mg/dl 이상으로 유도된 것을 확인한 후 4주간 γPGA를 섭취한 결과, 고과당식이로 인하여 증가된 중성지방 수치가 γPGA 섭취를 통하여 정상 수준인 200mg/이 이하로 낮아진 것으로 나타났다.
In the experimental group fed γPGA for 4 weeks after high fructose diet, total cholesterol and LDL-cholesterol levels were significantly decreased, and HDL-cholesterol was increased. Hypertriglyceridemia through high fructose diet Intake of γPGA for 4 weeks after confirming that the triglyceride level of the animals was averaged over 300mg / dl, the triglyceride level increased due to high fructose diet was increased through γPGA intake. It was found that the normal level was lowered below 200 mg /.
1) NC: 정상식이군, HC: 고과당식이군, HLP: 고과당식이+ 150 mg PGA/kg bw , HHP: 고과당식이+, 300mg PGA/kg bw. 1) NC: normal diet group, HC: high fructose diet group, HLP: high fructose diet + 150 mg PGA / kg bw, HHP: high fructose diet + 300 mg PGA / kg bw.
2) Values are expressed as the mean ± SEM, n=10 rats per group.
2) Values are expressed as the mean ± SEM, n = 10 rats per group.
3-3: 3-3: 간내Liver 포도당-6- Glucose-6- 인산탈수소효소Phosphate Dehydrogenase mRNAmRNA 유전자 발현 Gene expression
포도당-6-인산탈수소효소의 mRNA를 실시간 RT-PCR로 측정한 결과, γPGA의 섭취시 포도당-6-인산탈수소효소 유전자의 발현을 유의하게 억제하였으며, 이는 고과당식이로 인하여 간조직내 증가된 G6PDH 효소의 활성이 γPGA 섭취를 통하여 감소한 것으로 나타났다.
Glucose-6-phosphate dehydrogenase mRNA was measured by RT-PCR in real time, and the expression of glucose-6-phosphate dehydrogenase gene was significantly inhibited when γPGA was ingested. The activity of G6PDH enzyme was shown to be decreased by γPGA intake.
실시예Example 4: 4: 폴리감마글루탐산의Of polygammaglutamic acid 중성지방 개선 Triglyceride improvement 인체시험Human test
폴리감마글루탐산의 중성지방 개선 기능성을 인체에서 확인하기 위해 인체시험을 실시하였다. 피험자는 대조군과 실험군으로 나뉘어 총 8주간 위약 또는 시험원료를 섭취하였다. 본 연구에 참여한 대조군의 경우 제품군과 동일하게 복용 전, 복용 4주 후, 복용 8주 후에 혈액검사를 받고 전문의와 영양사와의 상담을 통해 혈중 지질이 개선될 수 있도록 식사요법 및 생활습관을 상담하였다. 섭취는 일일 1회 점심 식사 2시간 직전에 섭취하였으며, 시험은 이중 맹검법으로 실시하였다. 임상시험을 실시하는 서울 백병원 산하의 임상영양연구소에 연구원 겸 영양사가 일정한 간격(1회/주)을 두고 전화 및 직접 상담을 통해 피험자의 복용 여부를 확인하고 기타 발생하는 문제점이나 부작용 등을 검사하고, 식사상담 및 제품에 대한 지식 등을 전달하며, 규칙적으로 모니터링 하였다. 임상시험은 8주간 진행되며 복용 전, 복용 4주 후, 그리고 마지막으로 복용 후 8주가 되면 임상시험의 복용기간을 종료하였다. 복용이 종료되는 날의 다음날 또는 그 다음날에 연구기관인 서울 백병원 비만센터에 소집하게 되며, 복용에 따른 여러 평가지표를 측정, 조사하여 최종적인 평가를 종료하였다.Human tests were conducted to confirm the triglyceride-improving functionality of polygammaglutamic acid in the human body. Subjects were divided into control and experimental groups and received either placebo or test ingredients for a total of 8 weeks. In the case of the control group who participated in this study, they took blood tests before taking, 4 weeks after taking, and 8 weeks after taking the diet, and consulted a dietary practitioner and lifestyle to improve blood lipids by consulting a specialist and dietitian. . The intake was taken 2 hours before lunch once a day and the test was performed by double blind method. Researchers and dietitians at the Clinical Nutrition Research Institute under the Seoul Paik Hospital conducting clinical trials are provided at regular intervals (once / week) to check whether or not the subjects are taken through telephone and direct consultations, and to check other problems or side effects. It also provided regular monitoring, meal counseling, and product knowledge. The trial lasted for eight weeks and the duration of the study was terminated before, after four weeks, and finally after eight weeks. The day after the end of the dose or the day after the end of the session, the research institute was convened at the Obesity Center, Seoul Paik Hospital.
피험자 선정기준은 연령 만 19세 이상 65세 이하 남녀로 혈중 콜레스테롤 수치가 200~260mg/dl로 기준을 정하였으며, SAS 또는 SPSS PC program 이용, 결과는 평균 표준편차로 표시하였으며, 임상 전후의 자료 비교는 Paired t-test, 실험군들과 대조군간의 비교는 t t-test, ANOVA, Multiple range test에 의해 유의성 검증(P<0.05)하였으며, 인자들간의 상관관계는 Pearson's correlation method를 사용하였다.
The subjects were selected from 19 to 65 years of age. The blood cholesterol level was set at 200 ~ 260mg / dl. The results were expressed as standard deviation using SAS or SPSS PC program. The paired t-test, the comparison between the experimental group and the control group were tested for significance by the t t-test, ANOVA, and multiple range test (P <0.05). The correlation between factors was Pearson's correlation method.
병력 및 약물 투여력 조사
인구, 사회학적 특성 조사Subject Consent and Demographic Survey
Medical history and drug dosage
Population and Sociological Characterization
기초식이조사Basic Dietary Survey
- 간기능 검사 : GOP, GPT, protein, albumin, alkaline phosphatase, bilirubin, γ-GTP
- 혈청지질 검사 : 총콜레스테롤, 중성지방, LDL-콜레스테롤, HDL-콜레스테롤
- 당질대사 검사 : glucose
- 신장기능 검사 : BUN, creatinine
- 갑상선 기능검사 : TSH
- 전해질 검사 : Na, K, Cl, calcium/phosphorus
- 통풍 검사 : uric acid
- 뇨 검사 : protein, glucose, blood, ketone -Hematological test: Routine CBC test such as WBC, RBC, Hemoglobin, Hematocrit, MCV
-Liver function test: GOP, GPT, protein, albumin, alkaline phosphatase, bilirubin, γ-GTP
Serum lipid test: Total cholesterol, triglycerides, LDL-cholesterol, HDL-cholesterol
-Glucose test: glucose
Kidney function test: BUN, creatinine
Thyroid function test: TSH
-Electrolyte test: Na, K, Cl, calcium / phosphorus
-Gout test: uric acid
Urine test: protein, glucose, blood, ketone
순응도평가Compliance assessment
4-1: 혈청 지질 검사 결과4-1: Serum Lipid Test Results
8주 후에 총 콜레스테롤은 PGA 군에서 16.76mg/dl 감소하고, 위약군에서 17.42mg/dl 감소하여 위약군이 더 많이 감소한 것으로 나타났으나 통계적으로 유의하지는 않았다(p=0.937). 두 군 간의 8주 후에 중성지방을 비교한 결과, PGA 군에서 44.62mg/dl 감소하였고, 위약군에서는 31.37mg/dl 증가하여 두 군 간의 통계적으로 유의한 차이를 나타냈다(p=0.029). HDL-콜레스테롤은 PGA 군에서 1.67mg/dl 감소하였고, 위약군에서 4.63mg/dl 감소하였으나 군 간의 유의한 차이는 없었다(p=0.260). LDL-콜레스테롤은 PGA 군에서 17.24mg/dl 감소하고, 위약군에서 19.21mg/dl 감소한 것으로 나타났으나 두 군 간의 통계적으로 유의한 차이는 나타나지 않았다(p=0.816).
After 8 weeks, total cholesterol decreased by 16.76 mg / dl in the PGA group and 17.42 mg / dl in the placebo group, which was further decreased in the placebo group, but not statistically significant (p = 0.937). The comparison of triglycerides after 8 weeks between the two groups showed a 44.62 mg / dl decrease in the PGA group and a 31.37 mg / dl increase in the placebo group, indicating a statistically significant difference between the two groups (p = 0.029). HDL-cholesterol decreased by 1.67 mg / dl in the PGA group and 4.63 mg / dl in the placebo group, but there was no significant difference between the groups (p = 0.260). LDL-cholesterol was decreased 17.24 mg / dl in the PGA group and 19.21 mg / dl in the placebo group, but there was no statistically significant difference between the two groups (p = 0.816).
(n=19)Placebo
(n = 19)
(n=21)PGA
(n = 21)
Cholesterol
(mg/dl)Total
Cholesterol
(mg / dl)
(mg/dl)Triglyceride
(mg / dl)
Cholesterol
(mg/dl)HDL-
Cholesterol
(mg / dl)
Cholesterol
(mg/dl)LDL-
Cholesterol
(mg / dl)
1) p-value by t-test 1) p-value by t-test
2) p-value by paired t-test
2) p-value by paired t-test
4-2: 신체계측 및 4-2: Anthropometric and 체성분Body composition 분석 결과 Analysis
8주 후에 체중변화를 비교한 결과, PGA 군에서 1.57kg 감량되었고, 위약군은 0.39kg 증가하여 PGA 군에서 더 감량이 된 것으로 나타났으며, 통계적으로 유의한 차이를 나타내었다(p=0.046). 군 간의 8주 후에 BMI를 비교한 결과도 PGA군이 0.60kg/m2 감소하였고, 0.17kg/m2 증가하였으나 두 군 간의 유의한 차이는 없었다(p=0.057). 8주 후에 허리둘레는 PGA 군은 1.04cm 감소하였고, 위약군은 0.05cm 증가하였으나, 군 간의 유의한 차이는 없었으며(p=0.426), 엉덩이둘레는 PGA 군은 0.95cm 감소하였고, 위약군은 0.46cm 감소하여 PGA 군이 더 감소하였으나 통계적으로 유의한 차이는 없었다(p=0.595). 두 군 간의 체지방량을 비교한 결과, PGA 군이 1.94kg 감소하였고, 위약군은 0.24kg 감소하여 PGA 군에서 더 감소하였으나, 군 간의 유의한 차이는 나타나지 않았다(p=0.159). 8주 후에 체지방률을 비교한 결과, PGA 군이 0.03% 감소하였고, 위약군은 0.55% 감소하였으나, 두 군 간의 차이는 통계적으로 유의하지 않았다(p=0.683). 제지방량은 PGA 군이 0.01kg 감소하였고, 위약군에서는 0.61kg 증가하였으나 통계적으로 유의한 차이는 나타나지 않았다(p=0.494).
After 8 weeks, the weight change was 1.57kg in the PGA group and 0.39kg in the placebo group, which was further reduced in the PGA group, showing a statistically significant difference (p = 0.046). After 8 weeks, the PGA group showed 0.60 kg / m 2 reduction and 0.17 kg / m 2 increase, but there was no significant difference between the two groups (p = 0.057). After 8 weeks, the waist circumference decreased by 1.04 cm in the PGA group and increased by 0.05 cm in the placebo group, but there was no significant difference between the groups (p = 0.426). The hip circumference decreased by 0.95 cm in the PGA group and 0.46 cm in the placebo group. The PGA group decreased further, but there was no statistically significant difference (p = 0.595). As a result of comparing the fat mass between the two groups, the PGA group decreased by 1.94 kg and the placebo group decreased by 0.24 kg, which was further reduced in the PGA group, but there was no significant difference between the groups (p = 0.159). After 8 weeks, body fat percentage was compared by 0.03% in the PGA group and 0.55% in the placebo group, but the difference between the two groups was not statistically significant (p = 0.683). Fat mass decreased 0.01 kg in the PGA group and 0.61 kg in the placebo group, but there was no statistically significant difference (p = 0.494).
(kg)weight
(kg)
(kg/m2)BMI
(kg / m 2 )
(cm)Waist circumference
(cm)
(kg)Body fat mass
(kg)
(%)Body fat percentage
(%)
(kg)Lean body mass
(kg)
1) p-value by t-test 1) p-value by t-test
2) p-value by paired t-test
2) p-value by paired t-test
4-3: 생화학적 검사 결과4-3: Biochemical Test Results
8주 후에 생화학적 검사 결과, Glucose는 PGA 군에서 3.18mg/dl 증가하였고, 위약군은 1.81mg/dl 감소하였으며, 통계적으로 유의한 차이가 나타났다(p=0.014). 그 외의 생화학적 검사 결과, PGA 군과 위약군의 모든 항목에서 유의한 차이는 나타나지 않았고, 모두 정상범위 내에 있었다. 임상시험 전후의 군 내 비교 결과, PGA 군에서는 Glucose와 Cl이 통계적으로 유의한 변화가 나타났고(p=0.042, p=0.027), 위약군에서는 Creatinine이 통계적으로 유의한 변화가 나타났다(p=0.002).
After 8 weeks, the biochemical test showed that Glucose increased by 3.18 mg / dl in the PGA group and 1.81 mg / dl in the placebo group, with statistically significant difference (p = 0.014). All other biochemical tests showed no significant differences in all items in the PGA and placebo groups, all within the normal range. In the group before and after the clinical trials, Glucose and Cl showed statistically significant changes in the PGA group (p = 0.042, p = 0.027) and creatinine showed a statistically significant change in the placebo group (p = 0.002). .
(mg/dl)Glucose
(mg / dl)
(g/dl)Protein
(g / dl)
(IU/L)ALP
(IU / L)
(mmol/L)Na
(mmol / L)
(mmol/L)Cl
(mmol / L)
1) p-value by t-test 1) p-value by t-test
2) p-value by paired t-test
2) p-value by paired t-test
이상으로, 본 발명 내용의 특정한 부분을 상세히 기술하였는바, 당업계의 통상의 지식을 가진 자에게 있어서, 이러한 구체적 기술은 단지 바람직한 실시양태일 뿐이며, 이에 의해 본 발명의 범위가 제한되는 것이 아닌 점은 명백할 것이다. 따라서 본 발명의 실질적인 범위는 첨부된 청구항들과 그것들의 등가물에 의하여 정의된다고 할 것이다.
While the present invention has been particularly shown and described with reference to specific embodiments thereof, those skilled in the art will appreciate that such specific embodiments are merely preferred embodiments, It will be obvious. It is therefore intended that the scope of the invention be defined by the claims appended hereto and their equivalents.
<110> BioLeaders <120> Composition for Improving Triglyceride Containing Poly-Gamma-Glutamic Acid <130> P12-B233 <160> 12 <170> KopatentIn 2.0 <210> 1 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 1 cgtgggccgc cctaggcacc a 21 <210> 2 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 2 ctctttgatg tcacgcacga tttc 24 <210> 3 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 3 ctgcgagcac gagacgtcta tag 23 <210> 4 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 4 tcattgtcac tggtcaactc cagc 24 <210> 5 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 5 cggtttcaga agctctgctc 20 <210> 6 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 6 gccacctctt tgctctgctc 20 <210> 7 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 7 ctcaggtcat gttggaaacc 20 <210> 8 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 8 agacagggag ttctcagatg 20 <210> 9 <211> 17 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 9 tgctcccagc tgcaggc 17 <210> 10 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 10 agacagggag ttctcagatg 20 <210> 11 <211> 19 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 11 ccgccaagca gagggtcac 19 <210> 12 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 12 gcattcaggg ctaacatcca act 23 <110> BioLeaders <120> Composition for Improving Triglyceride Containing Poly-Gamma-Glutamic Acid <130> P12-B233 <160> 12 <170> Kopatentin 2.0 <210> 1 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 1 cgtgggccgc cctaggcacc a 21 <210> 2 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 2 ctctttgatg tcacgcacga tttc 24 <210> 3 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 3 ctgcgagcac gagacgtcta tag 23 <210> 4 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 4 tcattgtcac tggtcaactc cagc 24 <210> 5 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 5 cggtttcaga agctctgctc 20 <210> 6 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 6 gccacctctt tgctctgctc 20 <210> 7 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 7 ctcaggtcat gttggaaacc 20 <210> 8 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 8 agacagggag ttctcagatg 20 <210> 9 <211> 17 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 9 tgctcccagc tgcaggc 17 <210> 10 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 10 agacagggag ttctcagatg 20 <210> 11 <211> 19 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 11 ccgccaagca gagggtcac 19 <210> 12 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 12 gcattcaggg ctaacatcca act 23
Claims (4)
A pharmaceutical composition for improving triglyceride in blood containing polygamma glutamic acid having a molecular weight of 100 Da to 5,000 kDa or a salt thereof as an active ingredient.
The pharmaceutical composition according to claim 1, wherein the salt is selected from the group consisting of sodium salt, potassium salt, calcium salt, magnesium salt, ammonium salt and zinc salt.
A health functional food for improving triglyceride in blood containing polygamma glutamic acid having a molecular weight of 100 Da to 5,000 kDa or a salt thereof as an active ingredient.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR101054808B1 (en) * | 2010-11-10 | 2011-08-05 | 주식회사 바이오리더스 | Composition for improving cholesterol containing poly-gamma glutamic acid |
| KR20120015206A (en) * | 2010-08-11 | 2012-02-21 | 한국식품연구원 | Preventing and treating composition for obesity comprising polygammaglutamic acid |
| KR101155079B1 (en) * | 2011-02-09 | 2012-06-11 | (주) 엔유씨생활과건강 | Composition for use of suppression of blood glucose increase and inhibition of obesity comprising gamma-polyglutamic acid and galated catechin |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20120015206A (en) * | 2010-08-11 | 2012-02-21 | 한국식품연구원 | Preventing and treating composition for obesity comprising polygammaglutamic acid |
| KR101054808B1 (en) * | 2010-11-10 | 2011-08-05 | 주식회사 바이오리더스 | Composition for improving cholesterol containing poly-gamma glutamic acid |
| KR101155079B1 (en) * | 2011-02-09 | 2012-06-11 | (주) 엔유씨생활과건강 | Composition for use of suppression of blood glucose increase and inhibition of obesity comprising gamma-polyglutamic acid and galated catechin |
Non-Patent Citations (1)
| Title |
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| 논문1: 계명대학교 대학원 공중보건학과 * |
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