KR20150015305A - Pharmaceutical composition comprising the lees extract of korean rice wine as an effective component for prevention or treatment of obesity and health functional food comprising the same - Google Patents
Pharmaceutical composition comprising the lees extract of korean rice wine as an effective component for prevention or treatment of obesity and health functional food comprising the same Download PDFInfo
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- KR20150015305A KR20150015305A KR1020130091213A KR20130091213A KR20150015305A KR 20150015305 A KR20150015305 A KR 20150015305A KR 1020130091213 A KR1020130091213 A KR 1020130091213A KR 20130091213 A KR20130091213 A KR 20130091213A KR 20150015305 A KR20150015305 A KR 20150015305A
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Abstract
Description
본 발명은 주박(酒粕) 추출물을 유효성분으로 함유하는 비만(Obesity)의 예방 또는 치료용 약학적 조성물 및 건강 기능 식품에 관한 것으로서, 보다 구체적으로는, 주박의 에탄올(Ethanol) 추출물로부터 제조되는 에틸아세테이트(Ethylacetate) 분획물을 유효성분으로 함유하는 비만의 예방 또는 치료용 약학적 조성물 및 건강 기능 식품에 관한 것이다.The present invention relates to a pharmaceutical composition and a health functional food for the prevention or treatment of obesity containing an extract of Lactococcus spp. As an active ingredient and more specifically to a pharmaceutical composition for preventing or treating obesity comprising ethyl The present invention relates to a pharmaceutical composition and a health functional food for preventing or treating obesity containing an ethylacetate fraction as an active ingredient.
최근 경제수준 및 삶의 질 향상과 의료의 최첨단화 과정을 지나고 있는 시점에도 불구하고 21세기 들어 건강에 대한 개념이 바뀌고 있다. 과거에는 단순질병이 없는 건강한 상태를 건강하다고 생각했으나 최근에는 신체적, 정신적, 영감적, 사회적 질서의 최적상태를 의미한다. 미국 암학회의 전문지 'New England Journal of Medicine' 최신호에 유지니아 칼레박사는 1982년부터 암환자가 아닌 사람 90만명을 대상으로 16년 간 추적 조사한 결과 과체중이나 비만인 사람이 암으로 사망할 가능성은 정상인에 비해 남녀 모두 20% 이상 심각하게 나타나는 것으로 밝혀졌다.Despite the recent economic and quality of life and the progress of health care, the concept of health is changing in the 21st century. In the past, I thought that a healthy condition without simple diseases was healthy, but recently it means the optimal state of physical, mental, inspirational, and social order. In a recent issue of the American Cancer Society's New England Journal of Medicine, Dr. Guyenia Calais has conducted a follow-up study of 900,000 people who have not had cancer since 1982, and found that overweight or obese people are likely to die from cancer Both men and women were found to be more than 20% serious.
일반적으로 비만이란 일반적으로 과다한 체지방을 가진 상태를 의미하는 것으로, 체지방이 전체 체중에서 차지하는 비율이 남자의 경우 25%, 여자의 경우 30% 이상일 때를 비만으로 보고 있으며, 아울러 체중(kg)을 신장의 제곱(m2)으로 나눈 값으로 산출되는 체질량 지수(BMI: body mass index)가 30 이상인 경우 역시 이를 비만으로 간주하고 있다.In general, obesity refers to a condition with excessive body fat. The proportion of body fat in total body weight is 25% for men and 30% for women. The body weight (kg) The body mass index (BMI), which is calculated by dividing the body mass index by the square (m 2 ) of the body mass index (BMI) of 30 or more, is also regarded as obesity.
세계보건기구(WHO)에서는 아시아인의 인종적 특성과 비만 관련 건강 위험성을 감안해 체질량지수 23 이상이면 과체중, 25 이상이면 비만으로 분류하고 있다. 비만의 원인으로는 유전적 요인, 환경적 요인, 에너지 대사 이상 등이 있으며, 비만의 종류에는 제공되는 원인에 따라서 단순성(1차성) 비만과 증후성(2차성) 비만으로 분류할 수 있다. 상기 단순성(1차성) 비만은 칼로리의 과다 섭취와 이의 체내 소비 부족으로 잉여 에너지가 몸 안의 지방으로 축적돼 나타나는 경우이며, 비만 환자의 대부분을 차지하고 있다. 아울러 이는 과식이나 폭식, 불규칙한 식습관, 운동부족, 우울증이나 불안, 스트레스 등과 밀접한 관계가 있는 것으로 알려져 있다. 상기 증후성(2차성) 비만의 경우는 갑상선 기능 저하증, 부신 피질 호르몬 과다분비, 다낭성 난소 증후군 등과 같은 질병이나 경구용 피임약, 신경안정제, 스테로이드 호르몬제, 항히스타민 성분이 포함된 약물 등으로 인해 유발되는 것으로 알려져 있다. 이외에도 유아기에서부터 무절제한 고칼로리 식품의 섭취로 인한 소아비만도 이제는 비만의 한 종류로 자리잡고 있으며 사회적 문제로 대두되고 있는 실정이다.The World Health Organization (WHO) categorizes obesity as overweight if the BMI is above 23 and obesity above 25, considering the racial characteristics of Asians and the health risks associated with obesity. The causes of obesity are genetic factors, environmental factors, and energy metabolism abnormalities. The types of obesity can be classified into simple (primary) obesity and symptomatic (secondary) obesity according to the causes provided. The above-mentioned simplicity (primary) obesity is a case where surplus energy is accumulated in the body fat due to an excessive intake of calories and a lack of consumption thereof, and it occupies most of obese patients. It is also known to be closely related to overeating, binge eating, irregular eating habits, lack of exercise, depression, anxiety, and stress. The above symptomatic (secondary) obesity is caused by diseases such as hypothyroidism, cortical hormone excess secretion, polycystic ovary syndrome and the like, oral contraceptives, neurotransmitters, steroid hormones, drugs containing antihistamine components . In addition, childhood obesity due to ingestion of high calorie foods from infancy is now becoming a kind of obesity and becoming a social problem.
과거에는 비만을 단순히 과식으로 인한 외적이며 사치스러운 문제라고 치부해 왔으나, 최근에는 고칼로리성 식습관과 교통수단의 발전에 따른 운동부족으로 인해 비만 환자가 급증하게 되었다. 이는 개인적인 문제일 뿐만 아니라 사회적인 문제로까지 확산되고 있으며, 이를 반영하듯 세계보건기구(WHO)에서는 1997년 비만을 만성 질환 중에 하나로 규정하였다.In the past, obesity has simply been regarded as an external and luxurious problem caused by overeating. Recently, obesity has been rapidly increasing due to the lack of exercise due to the development of high calorie eating habits and transportation. Not only is it a personal problem, but it is also spreading to social problems, and the World Health Organization (WHO) has defined obesity as one of the chronic diseases in 1997.
비만은 당뇨, 고혈압, 고지혈증, 담석증 등 많은 성인병을 유발하는 직접 또는 간접적인 원인이며, 최근 들어 비만으로 인한 강박관념으로 인해 폭식증이나 거식증 등의 식이 장애 환자들이 늘어나고 있다. 또한 여성의 경우는 보다 더 심각하여 수단과 방법을 가리지 않고 체중 감량을 시도하고 있다는 점에서 큰 문제점으로 지적되고 있다. 이러한 경우에는 이들에게 정서적, 직업적, 사회적, 경제적, 신체적 영역에서 심각한 문제를 불러오며, 심지어는 죽음까지도 초래하게 된다. 결국 비만은 신체적으로나 정신적으로 인간에게 치명적인 상처를 줄 수 있는 질환이며, 사회적으로나 경제적으로 엄청난 손실을 안겨줄 수 있다는 점에서 그 문제의 심각성은 크다고 할 수 있다.Obesity is a direct or indirect cause of diabetes, hypertension, hyperlipidemia, cholelithiasis and many other diseases. In recent years, diabetic patients such as bulimia and anorexia are increasing due to the obsession with obesity. It is also pointed out that women are more serious than men and try to lose weight regardless of means and methods. In these cases, they bring serious problems to their emotional, occupational, social, economic, and physical areas, and even death. In the end, obesity is a disease that can be fatal to humans both physically and mentally, and it can be said that the problem is serious in that it can cause enormous loss both socially and economically.
이러한 비만을 치료하기 위해 수행되는 치료법은 크게 식이요법, 운동요법과 약물요법으로 분류되어진다. 식이요법 및 운동요법은 의지력과 시간을 많이 할애해야 한다는 측면과 더불어 여가시간을 많이 가질 수 없는 현대인에게는 이들 요법만으로는 효과적인 성과를 달성하기가 쉽지 않다는 것이 가장 큰 단점으로 지적되고 있다. 또한 임상시험 결과에 따르면 식이요법과 운동요법만으로 체중 감량을 시도한 경우에 비해 약물 요법을 더불어 시행한 경우가 2년 후의 결과에 있어 체중 감량이 약 2배 정도 많아 졌을 뿐 아니라, 비만과 관련된 혈압, 혈당, 콜레스테롤 등과 같은 수치가 현저히 개선된 것으로 보고되었다. 따라서 비만치료에 있어 약물요법에 대한 비중 및 치료제 개발에 대한 관심이 증폭되어질 수밖에 없는 실정이다.The treatments to treat these obesity are largely categorized into diet, exercise and drug therapy. Diet therapy and exercise therapy have a lot of willpower and time, and the biggest drawback is that it is not easy for modern people who can not have much leisure time to achieve effective results by themselves. In addition, according to the results of the clinical study, the weight loss of the obesity-related blood pressure and the obesity-related blood pressure, Blood glucose, cholesterol, and the like. Therefore, the proportion of drug therapy in the treatment of obesity and interest in the development of therapeutic drugs are inevitable.
1990년대 중반 비만 유전자의 발견과 더불어 지방세포에서 생성되는 렙틴(leptin)이라는 호르몬이 식욕억제를 담당하는 역할을 하는 것으로 밝혀짐으로써 비만치료제 개발의 기폭제 역할을 하였다. 아울러 렙틴(leptin)과 상호작용을 하면서 식욕촉진 효과를 나타내는 것으로 알려진 뉴로펩타이트 Y(neuropeptide Y), 멜라민 농축 호르몬(melanin-concentrating hormone; MCH), 갈아닌(galanin) 및 오렉신(orexins) 등과 같은 오레시제닉 펩타이드(orexigenic peptides)와 더불어 식욕억제 효과가 있는 것으로 알려진 멜라노코틴(melanocortins), 밤베신(bombesin) 등과 같은 아노렉틱 펩타이드(anorectic peptides)들의 구조와 기능이 밝혀짐으로써 비만 치료제 개발의 중대한 전환기를 맞고 있는 실정이다.In the mid-1990s, along with the discovery of obesity genes, leptin, a hormone produced in adipocytes, was found to play a role in the suppression of appetite, thereby acting as a catalyst for the development of obesity drugs. It is also known that neuropeptide Y, melanin-concentrating hormone (MCH), galanin and orexins, which are known to exhibit an appetite-promoting effect while interacting with leptin In addition to orexigenic peptides, the structure and function of anorectic peptides such as melanocortins, bombesin, etc., which are known to have an appetite suppressant effect, We are in the process of turning around.
이에 편승하여 비만을 치료하기 위해 많은 노력들을 시도하였고, 실제로 여러 약물들의 개발을 이루었거나 임상시험 중이며, 특히 국내의 경우 새로운 약물이 소개될 때마다 선풍적인 인기를 끌고 있는 것도 사실이다. 이전에 비만 치료제로 흔히 사용되던 저칼로리, 고식이섬유 제제의 식사 대용제나 위장 팽창제 등은 비만을 치유하기 위한 주요 치료제 보다는 보조 요법제로 많이 사용되었으나, 그 효과에 대해 많은 의문점이 제기되고 있는 실정이다.It is also true that many attempts have been made to treat obesity, and have actually developed a number of drugs or are in clinical trials, especially in Korea, where new drugs are introduced and become popular. Previously, low-calorie, high-fiber dietary substitutes, and gastrointestinal swelling agents, which were previously used as obesity remedies, have been widely used as adjunctive therapies rather than major remedies for the treatment of obesity, but many questions have been raised about their effectiveness.
현재 비만 치료제로 널리 사용되는 식욕억제제의 경우, 뇌의 시상하부에 작용하여 식욕억제로 인한 체중 감량 효과를 나타내는 작용기전을 가지고 있으며, 이들 대부분은 중추 신경 흥분을 유발시켜 이의 작용을 유발하는 것으로 알려져 있 다. 국내에서 대표적인 식욕억제제로 사용중인 시부트라민(sibutramine, 상품명: 리덕틸)은 식욕 조절에 작용하는 신경호르몬인 세로토닌(serotonin)과 노르아드레날린(noradrenaline)의 재흡수를 동시에 억제시켜 식욕을 떨어뜨리는 약물이다. 그러나 이들 대부분의 식욕억제제의 경우, 교감 신경을 흥분시켜 혈압이나 심박출량이 증가하게 되고 결과적으로 심혈관계 환자에게 이들 약물 복용은 금기시되고 있다. 또한 일부 약물에서는 정신적, 신체적 의존성이 있는 것으로 알려져 있다.Currently, appetite suppressants, which are widely used for obesity treatment, have a mechanism of action that acts on the hypothalamus of the brain, resulting in loss of weight due to appetite suppression. Most of them induce central nervous excitement and induce its action have. Sibutramine (Reductil), a typical appetite suppressant in Korea, is a drug that reduces appetite by simultaneously inhibiting the reuptake of serotonin and noradrenaline, the neurohormones that control appetite. However, in most of these appetite suppressants, sympathetic nerves are excited to increase blood pressure and cardiac output, and consequently these drugs are contraindicated in cardiovascular patients. In addition, some drugs are known to have psychological and physical dependence.
최근 들어 중추신경계에 작용하는 식욕억제제와는 달리 말초적인 지방흡수 억제를 통해 비만을 치료하는 제니칼(Xenical, 성분명: orlistat)의 개발로 비만치료에 있어 획기적인 전환점을 마련하게 되었다. 제니칼은 지방 흡수에 필요한 소화효소인 리파아제(lipase)의 활성을 특이적으로 억제하는 가역적 활성 억제제로 음식물로부터 섭취되는 지방의 흡수를 약 30% 정도 줄여 체중 감소 효과를 나타내는 것으로 알려져 있다. 그러나 제니칼의 경우 투여 초기에 지방 변이나 절박성 대변, 복부 팽만 등의 부작용과 함께 지용성 비타민의 흡수를 저해하여 따로 비타민을 복용해야 하는 단점이 있으며, 갑상선 기능 저하증 환자나 담즙 분비 정지 환자의 경우 이 약의 복용이 금기시 되고 있다. 뿐만 아니라 음식 중 지방이 차지하는 비율이 총 칼로리의 20%를 넘지 않는 한국인의 경우 지방 흡수 억제에 한계가 있을 수 있어 체중 감량 효과에 의문시되고 있는 점도 간과할 수 없는 실정이다.Recently, the development of Xenical (orlistat), which treats obesity through inhibition of peripheral lipid absorption unlike an appetite inhibitor acting on the central nervous system, has made a significant turning point in the treatment of obesity. Xenical is a reversible activity inhibitor that specifically inhibits the activity of lipase, a digestive enzyme necessary for fat absorption, and is known to exhibit a weight reduction effect by reducing the absorption of fat from food by about 30%. However, in the case of Xenical, there are disadvantages such as fat side, urgent stool, abdominal distension and other side effects, and absorption of fat-soluble vitamins. Therefore, vitamin C should be taken separately. In patients with hypothyroidism or bile- Is being contraindicated. In addition, Korean people who do not exceed 20% of the total calories in the proportion of fat in the food may be limited in the inhibition of fat absorption, and the effect of weight loss is questionable.
또한, 기존의 서양의약품제재나 치료제들은 인체 생리학적인 분석을 해보면 외부의 강제적 요인이 많이 치우친 현상으로 선택적인 생약제재에 비해 안정적이고 자연생리학적인 기전에 그 기대가 미흡한 실정이다.In addition, existing Western medicines and medicines are more biased by external physiological analysis than conventional medicinal herbs, and they are less stable than natural medicines.
한편, 주박은 탁주 등의 발효된 술을 거르고 남은 찌꺼기를 말하며, 술지게미, 재강 또는 아레기 등으로 불린다. 일반적으로 탁주 제조시 원료 쌀의 도정→세미→침미→수절→증자 및 냉각→입국제조→주모(밑술)제조→1차 발효→2차 발효→숙성→제성으로 이루어지며, 이중 가장 중요한 공정인 발효공정은 누룩, 물 및 쌀 전분의 다양한 물리적, 화학적, 생물학적 반응을 통해 완성되며, 발효 후에는 상기의 제성 공정(체 등을 이용하여 물을 가하면서 탁주를 거르는 공정)을 통해 탁주 제품이 완성되며, 이때 걸러진 찌꺼기가 주박(lees of Korean rice wine)이다. 따라서, 주박은 상당량의 영양성분과 유용 생리활성 성분을 가지고 있는 것으로 잘 알려져 있다. 실제로 쌀을 주원료로 사용하는 탁주의 경우, 주박은 식품대용으로 이용된 바 있으며, 최근에는 기능성 화장품 소재로도 각광받고 있다. 그러나, 현재 국내에서의 주박 이용은 주로 주박내 알코올을 이용하여 식초를 만들거나, 향미성분을 이용하여 야채절임류 제조에 이용되며, 일부 친환경 비료 및 동물사료로 이용되고 있으나, 대부분은 폐기처리되고 있는 실정이다. On the other hand, Jukbu refers to the residue left after filtering fermented liquor such as Takju, and is called sake ji-gee, janggang, or argyu. Generally, in the production of Takju, it is made up of the raw rice → semi-semitransparent → salting → increase and cooling → immigration → manufacture → primer → primary fermentation → secondary fermentation → aging → fermentation, The process is completed through various physical, chemical and biological reactions of the yeast, water, and rice starch. After the fermentation, the Takju product is completed through the above-described sifting process (a process of filtering the takju with water using a sieve etc.) , And lees of Korean rice wine. Therefore, it is well known that apricot has a large amount of nutrients and useful physiologically active ingredients. Actually, in the case of Takju, which uses rice as its main ingredient, it has been used as a substitute for food, and recently, it has been attracting attention as a functional cosmetic material. However, in Korea, the use of alcoholic beverages is mainly used to make vinegar using alcohol in the alcoholic beverages, or to make vegetable pickles using flavor components, and is used as some environmentally friendly fertilizers and animal feeds. However, It is true.
주박에 관련된 연구는 주로 일본 청주에 집중되어 있으며, 특히 1990년대 침체된 일본 청주산업의 돌파구로 주박에서 유용생리활성을 검증하던 중, Saito 등의 연구진에 의해 청주 주박으로부터 항고혈압 활성을 가진 펩타이드를 분리, 보고(Saito 등, 1994. Biosci. Biotechnol. Biochem. 58: 1767~1771)하면서 활성화되었다. 이후 주박의 환경오염물질 제거 효능(Adachi 등, 2005. Chemosphere 58: 817~822), 미백효과 (Jeon 등, 2006. J. Agric. Food Chem. 54: 9827~9833) 및 알러지 억제효과(Kawamoto 등, 2011, Biosci. Biotechnol. Biochem. 75: 140~144) 등이 알려지면서 다양한 주박에 대한 연구가 진행 중에 있다. Studies related to apricot are concentrated mainly on Japanese sake. Especially, while verifying the useful physiological activity of apricot with breakthrough of the Japanese sake industry in the 1990s, Saito et al. Have found that peptides having antihypertensive activity (Saito et al., 1994. Biosci. Biotechnol. Biochem. 58: 1767-1771). In the present study, the effect of the extract on the removal of environmental pollutants (Adachi et al., 2005, Chemosphere 58: 817 ~ 822), whitening effect (Jeon et al., 2006. J. Agric. Food Chem. 54: 9827-9833) , 2011, Biosci. Biotechnol. Biochem. 75: 140-144) have been known, and various studies on apricot are underway.
국내에서는 최근 웰빙 열풍에 힘있어 탁주에 대한 사회적 수요가 증가되면서 다양한 막걸리가 개발, 제조되고 있으며, 백년초 분말과 키토올리고당을 첨가한 탁주(박상순 외, 2011. 한국키토산학회지, 16: 164~169)가 보고되는가 하면, 블루베리, 산수유, 손바닥선인장, 더덕, 감초, 복분자 등의 기능성 식물을 포함시킨 탁주도 개발되어 있다. 국내 탁주 연구는 주로 탁주제조와 관련된 꼬두밥 제조에 대한 연구, 전분당화 및 발효에 관련된 곰팡이국, 누룩과 효모에 관한 연구 및 가 탁주의 저장기간 연장 연구가 주로 이루어져 왔다(소명환 외, 1999, 한국식품영양학회지, 12: 427~432; 왕승진 등, 2012, 한국식품저장유통학회지, 19: 116~122). 그러나, 현재까지 탁주 및 이들의 주박에 대한 생리활성 연구는 초보적인 수준에 있는 실정이다. 국내의 탁주 및 주박의 생리활성에 대한 주요 연구로는, 보리, 밀, 및 상황버섯 등을 이용하여 제조된 다양한 코지를 사용하여 제조된 주박의 항균 활성 및 항산화 활성(김태영 외, 2010, 한국식품영양과학회지, 23: 299~305), 주박 추출물의 항산화 효과, procollagen 합성 촉진 및 MMP-1의 발현억제를 통한 주름개선효과(유정민 외, 2010, 한국생명과학회지, 20: 1838~1843), 탁주 주박 섭취에 따른 당뇨개선 효과(김순미, 조우군, 2006, 한국식생활문화학회지, 21: 638~643)가 보고되어 있다. In Korea, a variety of makgeolli has been developed and manufactured as the social demand for Takju has been increased due to the well-being craze in recent years. Takju (Paek Sang Soon et al., 2011. Korean Chitosan Journal, 16: 164 ~ 169) Has been reported, including blueberry, corn oil, palm cactus, dodok, licorice, and bokbunja including functional plants have been developed Takju. Studies on the production of rice koji related to the production of takju in Korea have mainly been carried out on the study of fungi, yeast and yeast related to starch saccharification and fermentation, and the study of extension of storage period of takju (Myomin et al., 1999, Journal of the Korean Society of Food Science and Nutrition, 12: 427 ~ 432; Wang Sangjin et al., 2012, Korea Food Research Journal, 19: 116 ~ 122). However, up to now, studies on physiological activity of Takju and their extracts have been at a basic level. The major researches on the physiological activity of takju and japon in Korea are antimicrobial activity and antioxidant activity of japonica prepared by using various koji prepared by using barley, wheat, and mushroom (Kim Tae Young et al., 2010, (Jungmin et al., 2010, The Korean Journal of Life Science, 20: 1838 ~ 1843), the antioxidative effect of procambium extract, the promotion of procollagen synthesis and the suppression of MMP-1 expression, (Kim, Soon Mi, Joukun, 2006, Korean Journal of Food Culture, 21: 638 ~ 643) have been reported.
주박을 이용한 제품개발 연구로는 주박을 첨가한 기능성 약과, 기능성 국수, 돼지고기 첨가물 등의 식품 개발 연구가 보고된 바 있으며(조은자 외, 2007, 동아시아식생활학회지, 17: 94~102; 원지희 외, 2006. 한국식생활문화학회지, 21: 565~570; 김순미 외, 2007. 한국식생활문화학회지, 22: 359~364), 주박을 첨가한 가식성 필름(이정훈 외, 2007, 한국생명과학회지, 17: 1562~1570) 및 주박으로부터 효모포자의 생산(임용성 외, 2004, 한국미생물생명공학회지 32: 184~189) 연구도 알려져 있다.The research on the development of the food using the Chinese cabbage has been reported as the functional food added with the Chinese cabbage, the functional noodle, the pork additive, etc. (Jo, Eunja et al., 2007, East Asian Journal of Food and Nutrition, 17: 94 ~ 102; , 2006. Korean Journal of Food Culture, 21: 565 ~ 570, Kim Sun-Mi et al., 2007. Korean Journal of Food Culture, 22: 359 ~ 364) : 1562 ~ 1570), and the production of yeast spores from the seeds (Invitrogen et al., 2004, Korean Society of Microbial Biotechnology, 32: 184 ~ 189).
주박과 관련된 특허문헌으로는 대한민국 등록특허 제10-1152636호 복분자 주박을 이용한 울외장아찌 및 그 제조방법(등록일자 2012년 5월 29일), 대한민국 등록특허 제10-1101313호 양조폐기물을 이용한 에탄올의 제조방법(등록일자 2011년 12월 26일), 대한민국 등록특허 제10-0736327호 청주 주박을 이용한 보습·미백·주름 개선의 기능성 천연화장료 및 그 제조방법(등록일자 2007년 6월 29일), 대한민국 등록특허 제10-0737862호 주류생산 부산물인 주박과 신규한 바실러스 속 균주를 함유한 기능성 유기질비료(등록일자 2007년 7월 4일), 대한민국 등록특허 제10-1119414호 막걸리박 가수분해물을 유효성분으로 포함하는 면역활성 증강용 조성물(등록일자 2012년 1월 26일) 등이 개시되어 있다.Korean Patent No. 10-1152636 discloses a method for producing an algae extract using bokbunja japon, and a method for producing the same. (Registration date May 29, 2012) Korean Patent No. 10-1101313 A method for producing ethanol using brewer's waste (Date of Registration December 26, 2011), Korean Patent No. 10-0736327 Functional Natural Cosmetics for Moisturizing, Whitening and Wrinkle Reducing Using Cheongju Bean Bran and Manufacturing Method Thereof (Date of Registration June 29, 2007) Korean Registered Patent No. 10-0737862 A functional organic fertilizer containing spirulina and a novel strain of Bacillus, which are by-products of alcohol production (registered on July 4, 2007), Korean Patent No. 10-1119414, (Registered on Jan. 26, 2012) and the like are disclosed.
그러나, 현재까지 주박 추출물의 비만세포 분화 억제를 통한 항비만 효과에 관하여는 어떠한 보고나 연구도 진행된 바가 없다. However, there have been no reports or researches on the anti-obesity effect of inhibiting the differentiation of mast cells in the extract of Chinese cabbage.
본 발명은 상기와 같이 폐기되는 주박으로부터 유용생리활성 물질을 회수하고, 주박의 생물자원으로서의 효용성을 증대시키며, 기존 비만 치료제의 부작용에 따른 위험성을 극복하기 위하여 안출된 것으로서, 본 발명에서 해결하고자 하는 과제는 폐기되고 있는 주박의 추출물을 유효성분으로 함유하는 비만의 예방 또는 치료용 약학적 조성물 및 상기 추출물을 포함하는 건강 기능 식품을 제공하고자 하는 것이다.DISCLOSURE OF THE INVENTION The present invention has been made in order to recover useful physiologically active substances from the wastes to be discarded as described above, to increase the utility of the wastes as biological resources, and to overcome the risk of side effects of existing therapeutic agents for obesity. It is an object of the present invention to provide a pharmaceutical composition for preventing or treating obesity, which contains an extract of obtusa as an active ingredient, and a health functional food comprising the extract.
상기와 같은 과제를 해결하기 위하여, 본 발명은 주박(酒粕) 추출물을 유효성분으로 함유하는 비만(Obesity)의 예방 또는 치료용 약학적 조성물을 제공한다.In order to solve the above-mentioned problems, the present invention provides a pharmaceutical composition for preventing or treating obesity containing an extract of Liquorice as an active ingredient.
상기 주박 추출물은 주박의 에탄올 추출물인 것이 바람직하다.Preferably, the beech extract is an ethanol extract of beech sprout.
상기 주박 추출물은 주박의 에탄올 추출물의 에틸아세테이트 분획물인 것이 바람직하다.It is preferable that the seed extract is an ethyl acetate fraction of an ethanol extract of seedlings.
상기 주박 추출물은 지방 세포의 형성 및 분화를 억제하는 것이 바람직하다.It is preferred that the extract of the present invention inhibits the formation and differentiation of adipocytes.
또한, 본 발명은 상기 본 발명의 주박 추출물을 포함하는 비만 개선용 건강 기능 식품을 제공한다.In addition, the present invention provides a health functional food for obesity improvement comprising the extract of the present invention of the present invention.
본 발명의 약학적 조성물 및 건강 기능 식품의 유효성분으로서의 주박 추출물, 특히, 주박의 에탄올 추출물 또는 에틸아세테이트 분획물은 마우스 전지방 세포주의 지방 세포 형성을 억제하고, 지방 형성 및 지질 대사와 관련된 PPARγ, 아디포넥틴 및 SCD-1 유전자의 발현을 감소시키는 효과가 있으므로, 상기 유효성분은 비만의 예방, 개선 및 치료용도로서 의약품 및 식품에 적용될 수 있다.The present invention relates to a pharmaceutical composition and an active ingredient of a health functional food which are effective for inhibiting adipocyte formation in mouse whole fat cell lines and inhibiting adipocytopenia associated with lipogenesis and lipid metabolism, And the expression of the SCD-1 gene, the active ingredient can be applied to medicines and foods for the purpose of prevention, improvement and treatment of obesity.
도 1은 본 발명의 주박 추출물, 즉, 주박 에탄올 추출물의 에틸아세테이트 분획물의 마우스 전지방 세포주인 3T3-L1 세포의 지방세포 형성 억제 효과를 나타낸 것이다.
도 2는 본 발명의 주박 추출물, 즉, 주박 에탄올 추출물의 에틸아세테이트 분획물을 마우스 전지방 세포주인 3T3-L1 세포에 처리한 후 본 발명의 주박 추출물, 바람직하게는 주박 에탄올 추출물, 보다 바람직하게는 주박 에탄올 추출물의 에틸아세테이트 분획물은의 발현 양상을 나타낸 것이다.
도 3은 본 발명의 주박 추출물, 즉, 주박 에탄올 추출물의 에틸아세테이트 분획물을 마우스 전지방 세포주인 3T3-L1 세포에 처리한 후 시간 경과별로 PPARγ 유전자의 발현 양상을 나타내는 것이다.FIG. 1 shows the inhibitory effect of the extract of Prunus persicae of the present invention, that is, the ethyl acetate fraction of Prunus persicae extract, on the adipocyte formation of 3T3-L1 cells, a mouse preadipocyte cell line.
FIG. 2 is a graph showing the results of the treatment of 3T3-L1 cells, a pre-adipocyte cell line, of the extract of the present invention, that is, the ethyl acetate fraction of the ethanol extract of the alcohol extract of the present invention, The ethyl acetate fraction of the ethanol extract shows the expression pattern of.
FIG. 3 shows the expression pattern of the PPAR gamma gene over time after treatment of the extract of the present invention, that is, the ethyl acetate fraction of the ethanol extract of Pueraria japonica, on the 3T3-L1 cells before the mouse adipose cell line.
이하, 본 발명을 상세하게 설명한다.Hereinafter, the present invention will be described in detail.
본 발명의 발명자들은 천연물 기원의 비만 치료용 물질을 개발하기 위하여 다양한 후보군에 대한 효능 실험을 거듭한 결과, 주박의 유기 용매 추출물이 마우스 전지방 세포주인 3T3-L1 세포의 지방세포 형성 억제 효과를 나타내고, 지방 형성과 지질 대사에 관련된 것으로 알려진 PPARγ, 아디포넥틴 및 SCD-1 유전자의 발현을 감소시킴을 확인함으로써 상기 주박의 유기 용매 추출물을 비만의 예방 또는 치료용 약학적 조성물 및 건강 기능 식품으로서의 적용 가능성을 제안한다.The inventors of the present invention have conducted various efficacy tests on various candidate groups in order to develop a substance for treating obesity originating from natural materials. As a result, the organic solvent extract of the Chinese cabbage showed an effect of inhibiting adipocyte formation of 3T3-L1 cells, , The expression of PPARγ, adiponectin and SCD-1 gene, which are known to be involved in lipogenesis and lipid metabolism, is reduced, thereby making it possible to apply the organic solvent extract of the present invention as a pharmaceutical composition for the prevention or treatment of obesity and as a health functional food I suggest.
따라서, 본 발명은 주박(酒粕) 추출물을 유효성분으로 함유하는 비만(Obesity)의 예방 또는 치료용 약학적 조성물을 제공한다.Accordingly, the present invention provides a pharmaceutical composition for the prevention or treatment of obesity, which comprises an extract of Aspergillus oryzae as an active ingredient.
본 발명의 "주박"은 청주, 맥주, 약주, 탁주 등의 양조주 또는 발효주의 제성 공정으로부터 얻어질 수 있으나, 여기에 한정되는 것은 아니다. 또한, 본 발명의 주박은 양조주나 발효주의 제조에 사용되는 효모의 종류, 발효 및 숙성 조건 등에 무관하게 어떠한 제조 공정을 통한 것이라도 무방하다.The "bean sprout " of the present invention can be obtained from a brewing process such as sake, beer, sake, takju, or a fermentation product, but is not limited thereto. In addition, the present invention is not limited to the type of yeast used in the manufacture of brewing or fermentation stock, fermentation and aging conditions, and the like.
바람직한 구체예로서, 본 발명의 주박 추출물은 탁주의 제성 공정으로부터 수거된 주박을 압착하여 수분함량을 감소시키고, 이를 유기용매로 추출하여 그 추출물을 필터 페이퍼를 사용하여 여과한 후 감압농축하여 제조될 수 있다.As a preferred embodiment, the extract of the present invention can be produced by extracting the extract from an organic solvent, filtering the extract by using a filter paper, and concentrating it under reduced pressure. .
상기 유기용매는 탄소수 1~4의 무수 또는 함수 저급 알코올일 수 있으며, 바람직하게는 에탄올, 보다 바람직하게는 80~95% 에탄올이다.The organic solvent may be an anhydrous or hydrated lower alcohol having 1 to 4 carbon atoms, preferably ethanol, more preferably 80 to 95% ethanol.
또 다른 바람직한 구체예로서, 본 발명의 주박 추출물은 탁주의 제성 공정으로부터 수거된 주박을 압착하여 수분함량을 감소시키고, 이를 에탄올로 추출하여 그 추출물을 필터 페이퍼를 사용하여 여과한 후 감압농축하여 분말화하고, 상기 분말화된 에탄올 추출물을 물에 현탁한 후 에틸아세테이트와 혼합하여 에틸아세테이트 분획물을 얻음으로써 제조될 수도 있다.In another preferred embodiment of the present invention, the extract of the present invention is obtained by compressing the extract of Takju collected from the process of preparing Takju, thereby reducing the water content. The extract is extracted with ethanol, the extract is filtered using filter paper, , Suspending the powdered ethanol extract in water, and then mixing with ethyl acetate to obtain an ethyl acetate fraction.
본 발명의 발명자들의 연구 결과에 따르면, 본 발명의 주박 추출물, 바람직하게는 주박 에탄올 추출물, 보다 바람직하게는 주박 에탄올 추출물의 에틸아세테이트 분획물은 지방 세포 형성 및 분화를 억제시킬 수 있다.According to the study results of the present inventors, it was found that the extract of the present invention, preferably the extract of japonica, more preferably the fraction of ethyl acetate of the japonica ethanol extract, can inhibit adipocyte formation and differentiation.
또한, 본 발명의 발명자들은 본 발명의 주박 추출물, 바람직하게는 주박 에탄올 추출물, 보다 바람직하게는 주박 에탄올 추출물의 에틸아세테이트 분획물이 지방 형성 및 지질 대사와 관련된 PPARγ, 아디포넥틴, SCD-1 유전자들의 발현을 감소시킬 수 있음을 확인하였다.In addition, the inventors of the present invention have found that the extracts of the present invention, preferably the extracts of japonica, more preferably the ethyl acetate fractions of the japonica ethanol extract, express PPARγ, adiponectin and SCD-1 genes associated with lipogenesis and lipid metabolism .
본 발명의 주박 추출물의 상기 설명된 지방 세포 형성과 분화의 억제 및 지방 형성과 지질 대사와 관련된 유전자의 발현 감소의 효과는 본 발명의 주박 추출물이 비만의 예방과 치료에 효과적으로 사용될 수 있음을 강력히 시사하는 것이다.The effect of inhibiting adipocyte formation and differentiation and the expression of genes associated with lipogenesis and lipid metabolism described above of the present invention of the present invention is strongly suggested that the extract of the present invention can be effectively used for the prevention and treatment of obesity .
본 발명의 주박 추출물을 포함하는 약학적 조성물은 각각의 사용 목적에 맞게 통상의 방법에 따라 산제, 과립제, 정제, 캡슐제, 현탁제, 에멀젼, 시럽, 에어로졸 등의 경구 제형, 멸균 주사용액의 주사제 등 다양한 형태로 제형화하여 사용할 수 있으며, 경구 투여하거나 정맥 내, 복강 내, 피하, 직장, 국소 투여 등을 포함한 다양한 경로를 통해 투여될 수 있다.The pharmaceutical composition comprising the extract of the present invention can be administered orally or parenterally in the form of powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols and the like, And may be administered by various routes including oral administration or intravenous, intraperitoneal, subcutaneous, rectal, topical administration, and the like.
이러한 약학적 조성물에는 추가적으로 담체, 부형제 또는 희석제 등이 더 포함될 수 있으며, 포함될 수 있는 적합한 담체, 부형제 또는 희석제의 예로는 락토오스, 덱스트로오스, 수크로오스, 솔비톨, 만니톨, 자일리톨, 에리쓰리톨, 말티톨, 전분, 아카시아 고무, 알지네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실리케이트, 셀룰로스, 메틸 셀룰로스, 비정질 셀룰로스, 폴리비닐 피롤리돈, 물, 메틸하이드록시벤조에이트, 프로필하이드록시벤조에이트, 탈크, 마그네슘 스테아레이트 및 광물유 등을 들 수 있다. Such pharmaceutical compositions may further comprise carriers, excipients or diluents, and examples of suitable carriers, excipients or diluents that may be included include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, But are not limited to, starch, acacia gum, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methylcellulose, amorphous cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, And the like.
또한, 본 발명의 약학적 조성물은 충전제, 항응집제, 윤활제, 습윤제, 향료, 유화제, 방부제 등을 추가로 더 포함할 수도 있다.In addition, the pharmaceutical composition of the present invention may further include a filler, an anti-coagulant, a lubricant, a wetting agent, a flavoring agent, an emulsifying agent, an antiseptic, and the like.
바람직한 구체예로서, 경구 투여를 위한 고형 제제에는 정제, 환제, 산제, 과립제, 캡슐제 등이 포함되며, 이러한 고형 제제는 상기 약학적 조성물에 적어도 하나 이상의 부형제, 예를 들면, 전분, 탄산칼슘, 수크로오스, 락토오스, 젤라틴 등을 혼합하여 제형화한다. 또한, 단순한 부형제 이외에 마그네슘 스테아레이트, 탈크 등과 같은 윤활제가 사용될 수도 있다.In a preferred embodiment, the solid preparations for oral administration include tablets, pills, powders, granules, capsules and the like, which may contain at least one excipient, for example starch, calcium carbonate, Sucrose, lactose, gelatin and the like are mixed and formulated. In addition to simple excipients, lubricants such as magnesium stearate, talc, and the like may also be used.
바람직한 구체예로서, 경구용 액상 제제로는 현탁제, 내용액제, 유제, 시럽제 등이 예시될 수 있으며, 흔히 사용되는 단순 희석제인 물, 액체 파라핀 이외에 여러 가지 부형제, 예를 들면, 습윤제, 감미제, 방향제, 보존제 등이 포함될 수 있다.Examples of the oral liquid preparation include suspensions, solutions, emulsions, syrups and the like. In addition to water and liquid paraffin which are commonly used simple diluents, various excipients such as wetting agents, sweeteners, Perfumes, preservatives, and the like.
바람직한 구체예로서, 비경구 투여를 위한 제제에는 멸균된 수용액제, 비수성용제, 현탁제, 유제, 동결건조제, 좌제 등을 예시할 수 있다. 비수성용제, 현탁제에는 프로필렌글리콜, 폴리에틸렌글리콜, 올리브 오일과 같은 식물성 기름, 에틸올레이트와 같은 주사 가능한 에스테르 등이 포함될 수 있다. 주사제에는 용해제, 등장화제, 현탁화제, 유화제, 안정화제, 방부제 등과 같은 종래의 첨가제가 포함될 수 있다.As a preferable specific example, the preparation for parenteral administration includes sterilized aqueous solutions, non-aqueous solvents, suspensions, emulsions, freeze-drying agents, suppositories, and the like. Examples of the non-aqueous solvent and suspending agent include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like. Injectables may include conventional additives such as solubilizers, isotonic agents, suspending agents, emulsifiers, stabilizers, preservatives, and the like.
본 발명의 약학적 조성물은 약제학적으로 유효한 양으로 투여한다. 본 발명에서, "약제학적으로 유효한 양"은 의학적 치료에 적용 가능한 합리적인 수혜/위험 비율로 질환을 치료하기에 충분한 양을 의미하며, 유효 용량 수준은 환자의 질환의 종류, 중증도, 약물의 활성, 약물에 대한 민감도, 투여 시간, 투여 경로 및 배출 비율, 치료 기간, 동시 사용되는 약물을 포함한 요소 및 기타 의학 분야에 잘 알려진 요소에 따라 결정될 수 있다. 본 발명의 약학적 조성물은 개별 치료제로 투여하거나 다른 치료제와 병용하여 투여될 수 있고, 종래의 치료제와 순차적으로 또는 동시에 투여될 수 있으며, 단일 또는 다중 투여될 수 있다. 상기한 요소들을 모두 고려하여 부작용 없이 최소한의 양으로 최대 효과를 얻을 수 있는 양을 투여하는 것이 중요하며, 이는 당업자에 의해 용이하게 결정될 수 있다.The pharmaceutical composition of the present invention is administered in a pharmaceutically effective amount. In the present invention, "pharmaceutically effective amount" means an amount sufficient to treat a disease at a reasonable benefit / risk ratio applicable to medical treatment, and the effective dose level will depend on the type of disease, severity, The sensitivity to the drug, the time of administration, the route of administration and the rate of release, the duration of the treatment, factors including co-administered drugs, and other factors well known in the medical arts. The pharmaceutical composition of the present invention may be administered as an individual therapeutic agent or in combination with other therapeutic agents, and may be administered sequentially or simultaneously with conventional therapeutic agents, and may be administered singly or multiply. It is important to take into account all of the above factors and to administer the amount in which the maximum effect can be obtained in a minimal amount without side effects, which can be easily determined by those skilled in the art.
바람직한 구체예로서, 본 발명의 약학적 조성물에서 주박 추출물의 유효량은 환자의 나이, 성별, 체중에 따라 달라질 수 있으며, 일반적으로는 체중 ㎏ 당 1 내지 5,000mg, 바람직하게는 100 내지 3,000mg을 매일 또는 격일 투여하거나 1일 1 내지 3회로 나누어 투여할 수 있다. 그러나, 투여 경로, 질병의 중증도, 성별, 체중, 연령 등에 따라서 증감될 수 있으므로 상기 투여량이 어떠한 방법으로도 본 발명의 범위를 한정하는 것은 아니다.In a preferred embodiment of the present invention, the effective amount of the extract of the present invention in the pharmaceutical composition of the present invention may vary depending on the age, sex and body weight of the patient. Generally, 1 to 5,000 mg, preferably 100 to 3,000 mg per kg of body weight, Or every other day or one to three times a day. However, the dosage may not be limited in any way because it may be increased or decreased depending on route of administration, severity of disease, sex, weight, age, and the like.
본 발명의 약학적 조성물은 다양한 경로를 통하여 대상에 투여될 수 있다. 투여의 모든 방식은 예상될 수 있는데, 예를 들면, 경구, 직장 또는 정맥, 근육, 피하, 자궁내 경막 또는 뇌혈관내(intracerebroventricular) 주사에 의해 투여될 수 있다.The pharmaceutical composition of the present invention can be administered to a subject through various routes. All modes of administration may be expected, for example, by oral, rectal or intravenous, intramuscular, subcutaneous, intra-uterine or intracerebroventricular injections.
본 발명에서 "투여"는 임의의 적절한 방법으로 환자에게 소정의 물질을 제공하는 것을 의미하며, 본 발명의 약학적 조성물의 투여 경로는 목적 조직에 도달할 수 있는 한 일반적인 모든 경로를 통하여 경구 또는 비경구 투여될 수 있다. 또한, 본 발명의 조성물은 유효성분을 표적 세포로 전달할 수 있는 임의의 장치를 이용해 투여될 수도 있다.In the present invention, "administration" means providing a predetermined substance to a patient by any suitable method, and the administration route of the pharmaceutical composition of the present invention is either oral or non-oral May be administered orally. The composition of the present invention may also be administered using any device capable of delivering an effective ingredient to a target cell.
본 발명에서 "대상"은, 특별히 한정되는 것은 아니지만, 예를 들어, 인간, 원숭이, 소, 말, 양, 돼지, 닭, 칠면조, 메추라기, 고양이, 개, 마우스, 쥐, 토끼 또는 기니아 피그를 포함하고, 바람직하게는 포유류, 보다 바람직하게는 인간을 의미한다.In the present invention, the term "object" includes, but is not limited to, human, monkey, cow, horse, sheep, pig, chicken, turkey, quail, cat, dog, mouse, rat, rabbit or guinea pig , Preferably a mammal, more preferably a human.
본 발명의 상기 설명된 주박 추출물은 약학적 조성물로서뿐만 아니라 비만의 개선용 건강 기능 식품으로서도 제공될 수 있다.The above described bee extract of the present invention can be provided not only as a pharmaceutical composition but also as a health functional food for improving obesity.
따라서, 본 발명은 본 발명은 상기 본 발명의 주박 추출물을 포함하는 비만 개선용 건강 기능 식품을 제공한다.Accordingly, the present invention provides a health functional food for obesity improvement comprising the extract of the present invention of the present invention.
본 발명의 주박 추출물을 포함하는 식품으로는, 예를 들어, 각종 식품류, 음료, 껌, 차, 비타민 복합제, 건강보조 식품류 등이 있고, 분말, 과립, 정제, 캡슐 또는 음료인 형태로 사용할 수 있다.The food of the present invention containing the extract of the present invention may be in the form of powder, granule, tablet, capsule or beverage, for example, various foods, beverages, gums, tea, vitamin complexes and health supplement foods. .
본 발명의 주박 추출물은 일반적으로 전체 식품 중량의 0.01 내지 15중량%로 가할 수 있으며, 건강음료 조성물은 100ml를 기준으로 0.02 내지 10g, 바람직하게는 0.3 내지 1g의 비율로 가할 수 있다.The extract of the present invention may be added in an amount of 0.01 to 15% by weight based on the total weight of the whole food, and the health beverage composition may be added in an amount of 0.02 to 10 g, preferably 0.3 to 1 g, based on 100 ml.
본 발명의 건강 기능 식품은 지시된 비율로 필수 성분으로서 상기 화합물을 함유하는 것 외에 식품학적으로 허용 가능한 식품보조 첨가제, 예컨대, 천연 탄수화물 및 다양한 향미제 등을 추가 성분으로서 함유할 수 있다. The health functional food of the present invention may contain, as an additional ingredient, a food-acceptable food-aid additive such as natural carbohydrates and various flavors, in addition to containing the above-mentioned compound as an essential ingredient in the indicated ratio.
상기 천연 탄수화물의 예로는 포도당, 과당 등의 단당류, 말토오스, 수크로오스 등의 이당류 및 덱스트린, 시클로덱스트린 등의 다당류와 같은 통상적인 당 및 자일리톨, 소르비톨, 에리쓰리톨 등의 당알코올이 있다. 상기 천연 탄수화물의 비율은 본 발명의 건강 기능 식품 100ml 당 일반적으로 약 1 내지 20g, 바람직하게는 약 5 내지 12g을 사용한다. Examples of the natural carbohydrate include sugar sugars such as glucose, monosaccharides such as fructose, disaccharides such as maltose and sucrose, polysaccharides such as dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol and erythritol. The ratio of the natural carbohydrate is generally about 1 to 20 g, preferably about 5 to 12 g per 100 ml of the health functional food of the present invention.
상기 향미제로는 타우마틴, 레바우디오시드 A 또는 글리시르히진과 같은 스테비아 등의 천연 향미제 및 사카린, 아스파르탐 등의 합성 향미제를 사용할 수 있다. Examples of the flavoring agents include natural flavoring agents such as tautatin, rebaudioside A and stiglycerin such as glycyrrhizin, and synthetic flavoring agents such as saccharin and aspartame.
상기 외에 본 발명의 건강 기능 식품은 여러 가지 영양제, 비타민, 광물, 합성 풍미제 및 천연 풍미제 등의 풍미제, 착색제 및 중진제, 펙트산 및 그의 염, 알긴산 및 그의 염, 유기산, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알코올, 탄산음료에 사용되는 탄산화제 등을 함유할 수 있다. In addition to the above, the health functional food of the present invention may contain various kinds of nutrients, vitamins, minerals, flavors such as synthetic flavors and natural flavors, colorants and heavy stabilizers, pectic acid and its salts, alginic acid and its salts, Thickening agents, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, carbonating agents used in carbonated drinks, and the like.
그 밖에 본 발명의 건강 기능 식품은 천연 과일 주스 및 과일 주스 음료 및 야채 음료 등의 제조를 위한 과육을 함유할 수도 있다. 이러한 성분은 독립적으로 또는 조합하여 사용할 수 있다. 이러한 첨가제의 비율은 본 발명의 주박 추출물 100중량부 당 0.01 내지 20중량부의 범위에서 선택되는 것이 일반적이다.In addition, the health functional food of the present invention may contain flesh for producing natural fruit juice, fruit juice drink, vegetable drink and the like. These components may be used independently or in combination. The ratio of such additives is generally selected in the range of 0.01 to 20 parts by weight per 100 parts by weight of the extract of the present invention.
이하에서는 구체적인 실시예를 통하여 본 발명을 더욱 상세하게 설명한다. 하기 실시예는 본 발명의 바람직한 하나의 구체예일뿐이며, 본 발명이 하기 실시예에 기재된 범위로 한정하여 해석되는 것은 아니다.Hereinafter, the present invention will be described in more detail with reference to specific examples. The following examples are only a preferred embodiment of the present invention and are not to be construed as limiting the scope of the present invention.
[[ 실시예Example ]]
실시예Example 1: One: 주박The 추출물 및 유기용매 Extracts and organic solvents 분획물의Fraction 조제 pharmacy
2012년 강원도 횡성 탁주공장에서 제조된 주박을 회수하였다. 에탄올 추출물은 주박에 대해 10배 부피의 80% 에탄올(덕산, 한국)을 가하고 상온에서 48시간 동안 추출하였다. 추출물은 필터페이퍼(Whatman No. 2)를 사용하여 이물질을 제거한 후 회수하고, 이를 감압 농축하여 분말로 제조하고 사용 전까지 저온 보관하였다.We recovered the spruce produced at the Takju factory in Hoengseong, Gangwon Province in 2012. Ethanol extracts were prepared by adding 10 times volume of 80% ethanol (Duksan, Korea) to the beef sprouts and extracted at room temperature for 48 hours. The extract was recovered after removing foreign matter using a filter paper (Whatman No. 2) and concentrated under reduced pressure to prepare a powder, which was kept at low temperature until use.
상기 에탄올 추출 분말을 증류수에 현탁한 후, 동일 부피의 에틸아세테이트와 혼합하여 분획물을 얻었다. 에틸아세테이트 분획물은 감압 농축하여 분말화하고 사용전까지 저온 보관하였다.The ethanol extract powder was suspended in distilled water, and then mixed with the same volume of ethyl acetate to obtain fractions. The ethyl acetate fraction was concentrated under reduced pressure and powdered, and stored at low temperature until use.
실시예Example 2: 2: 주박The 추출물의 지방세포 형성 억제 효과 평가 Evaluation of inhibitory effect of extract on adipocyte formation
상기 실시예 1로부터 제조된 주박 에틸아세테이트 분획물의 지방세포 형성 억제 효과를 확인하기 위하여, 본 실시예에서는 주박 에탄올 추출물의 에틸아세테이트 분획물이 마우스 전지방 세포주인 3T3-L1 세포의 지방세포 형성과정에 미치는 영향을 조사하였다. In order to confirm the inhibitory effect on the adipocyte formation of the succinic acid ethyl acetate fraction prepared in Example 1, the ethyl acetate fraction of the succinic acid ethanol extract in this Example showed the effect on the adipocyte formation process of 3T3-L1 cells, The effect was investigated.
지방세포형성을 유도하면서 실시예 1로부터 얻은 주박 에탄올 추출물의 에틸아세테이트 분획물 100g/ml과 대조구로 DMSO를 각각 처리하였다. 그 결과, 분화 유도 후 대조구로 사용한 DMSO를 처리한 세포는 지방세포형성이 정상적으로 일어났다. 그러나, 주박 에탄올 추출물의 에틸아세테이트 분획물을 처리한 세포에서는 지방세포 형성이 억제되는 것을 확인하였다. 지방세포 형성 유무를 확실하게 구분하기 위하여 Oil red O 염색을 수행하였다. 그 결과, DMSO를 처리한 군에서는 지방세포의 입자가 붉게 염색됨을 확인하였고, 주박 에탄올 추출물의 에틸아세테이트 분획물을 처리한 경우에는 지방세포 형성이 억제됨을 확인하였다(도 1). 100 g / ml of the ethyl acetate fraction of the alcoholic ethanol extract obtained from Example 1 and DMSO as a control were each treated to induce adipocyte formation. As a result, the cells treated with DMSO as a control after induction of differentiation had normal adipocyte formation. However, it was confirmed that adipocyte formation was inhibited in the cells treated with the ethyl acetate fraction of the ethanol extract of Chenopodium album. Oil red O staining was performed to clearly distinguish adipocyte formation. As a result, in the group treated with DMSO, the adipocyte particles were found to be stained red, and when the ethacetate fraction of the ethanol extract of succulent was treated, adipocyte formation was inhibited (FIG. 1).
따라서, 본 발명의 주박 추출물은 지방세포 형성과 분화 억제 활성을 가지는 것으로 판단된다.Thus, the extract of the present invention has an adipocyte-forming and differentiation-inhibiting activity.
실시예Example 3: 3: 주박The 추출물의 지방 형성 및 지질 대사 관련 유전자 발현 억제 효과 평가 Evaluation of lipid formation and lipid metabolism-related gene expression inhibition of extracts
상기 실시예 1로부터 제조된 주박 에탄올 추출물의 에틸아세테이트 분획물에 의한 지방세포분화 억제과정 중 지방형성 및 지질대사와 관련된 PPAR γ, 아디포넥틴(Adiponectin) 및 SCD -1 유전자의 발현 변화를 확인하였다.During the process of adipocyte differentiation inhibiting by the ethyl acetate fraction of the ethanol extract jubak prepared from Example 1 it was confirmed that PPAR γ, adiponectin (Adiponectin) and the expression of genes associated with SCD -1 lipogenesis and lipid metabolism.
주박 에탄올 추출물의 에틸아세테이트 분획물로 처리된 마우스 전지방 세포주인 3T3-L1 세포로부터 Total RNA를 추출하고, PPAR γ, 아디포넥틴(Adiponectin) 및 SCD -1의 유전자 발현 양상을 확인하기 위하여 PPAR γ, 아디포넥틴(Adiponectin) 및 SCD -1에 각각 특이적인 프라이머를 사용하여 RT-PCR을 실시하였다.Total RNA extracts from the mouse around fat cell line, 3T3-L1 cells treated with ethyl acetate fraction of the ethanol extract and jubak, PPAR γ, adiponectin to confirm PPAR γ, adiponectin (Adiponectin) and gene expression patterns of SCD -1 ( Adiponectin ) and SCD- 1 using specific primers RT-PCR was performed.
그 결과, 주박 에탄올 추출물의 에틸아세테이트 분획물을 처리한 경우 세 유전자의 발현이 감소함을 확인할 수 있었다. 그 중에서도 지방세포형성의 최종 전사인자인 PPAR γ 유전자에서 현저하게 감소하는 것을 확인할 수 있었다(도 2).As a result, it was confirmed that the expression of the three genes was reduced when the ethyl acetate fraction of the ethanol extract of Jugaku was treated. It was confirmed that PPAR gamma gene, which is the final transcription factor of adipocyte formation, is remarkably decreased (FIG. 2).
또한, 마우스 전지방 세포주인 3T3-L1 세포의 분화유도 후 2일, 4일, 6일, 8일까지 주박 에탄올 추출물의 에틸아세테이트 분획물을 처리한 후 PPAR γ 유전자의 발현을 확인한 결과, 대조군은 시간이 경과됨에 따라 PPAR γ 유전자의 발현이 계속적으로 증가하는 반면, 주박 에탄올 추출물의 에틸아세테이트 분획물을 처리한 실험군은 6일이 되는 날부터 발현이 억제되기 시작하여 8일이 되는 시점에는 PPAR γ 유전자의 발현이 완전히 억제됨을 확인하였다(도 3).After the induction of differentiation of 3T3-L1 cells, the expression level of the PPAR gamma gene was examined after 2 days, 4 days, 6 days, and 8 days of the ethyl acetate fraction of the ethanol extract of the alcoholic extracts. As a result, whereas the expression of PPAR γ gene increases continuously as the elapsed, the time when the test group treated with the ethyl acetate fraction of jubak ethanol extract is 8 to start the expression is inhibited from
이상의 결과로부터, 본 발명의 주박 추출물은 지방세포 형성에 관여하는 PPARγ, 아디포넥틴(Adiponectin) 및 SCD -1의 유전자의 발현을 감소시키는 효과가 있으며, 이러한 효과로부터 본 발명의 주박 추출물은 비만의 예방, 치료 및 개선을 위한 용도에 적용 가능함을 알 수 있다.From the above results, jubak extract of the present invention has the effect of reducing the PPARγ, adiponectin (Adiponectin) and the gene expression of the SCD -1 involved in adipocyte formation, jubak extract of the present invention from this effect is prevention of obesity, It can be understood that the present invention is applicable to applications for treatment and improvement.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| KR20190020470A (en) * | 2017-08-21 | 2019-03-04 | 임재록 | Makgeolli residue mixed pill and production method thereof |
| US10973810B2 (en) | 2017-01-06 | 2021-04-13 | Yumanity Therapeutics, Inc. | Methods for the treatment of neurological disorders |
| US11873298B2 (en) | 2017-10-24 | 2024-01-16 | Janssen Pharmaceutica Nv | Compounds and uses thereof |
| US11970486B2 (en) | 2016-10-24 | 2024-04-30 | Janssen Pharmaceutica Nv | Compounds and uses thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| US11970486B2 (en) | 2016-10-24 | 2024-04-30 | Janssen Pharmaceutica Nv | Compounds and uses thereof |
| US10973810B2 (en) | 2017-01-06 | 2021-04-13 | Yumanity Therapeutics, Inc. | Methods for the treatment of neurological disorders |
| KR20190020470A (en) * | 2017-08-21 | 2019-03-04 | 임재록 | Makgeolli residue mixed pill and production method thereof |
| US11873298B2 (en) | 2017-10-24 | 2024-01-16 | Janssen Pharmaceutica Nv | Compounds and uses thereof |
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