KR20200125156A - Composition for improvementing, preventing or treating obesity and metabolic diseases comprising fractions or extract of pepper leave - Google Patents
Composition for improvementing, preventing or treating obesity and metabolic diseases comprising fractions or extract of pepper leave Download PDFInfo
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- KR20200125156A KR20200125156A KR1020190048997A KR20190048997A KR20200125156A KR 20200125156 A KR20200125156 A KR 20200125156A KR 1020190048997 A KR1020190048997 A KR 1020190048997A KR 20190048997 A KR20190048997 A KR 20190048997A KR 20200125156 A KR20200125156 A KR 20200125156A
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- South Korea
- Prior art keywords
- red pepper
- extract
- pepper leaf
- fat
- obesity
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Abstract
Description
본 발명은 비만 및 대사성질환 개선, 예방 또는 치료용 조성물에 관한 것으로, 고춧잎 추출물을 유효성분으로 함유하여, 전지방세포 분화와 지방 축적을 억제하며, 체중과 체지방의 증가를 감소시키며, 혈청 내 엔도톡신, 중성지방 및 총 콜레스테롤 농도를 낮추고, 혈청 내 지방분화 관련 호르몬의 발현을 억제함으로써 비만 및 대사성질환의 개선, 예방 및 치료를 위한 기능성 식품 및 약제 등에 유용하게 이용될 수 있다.The present invention relates to a composition for improving, preventing or treating obesity and metabolic diseases, containing red pepper leaf extract as an active ingredient, inhibiting proliferative cell differentiation and fat accumulation, reducing weight and body fat increase, and endotoxin in serum , It can be usefully used in functional foods and drugs for improvement, prevention and treatment of obesity and metabolic diseases by lowering the concentration of triglycerides and total cholesterol, and inhibiting the expression of hormones related to differentiation in serum.
비만은 과다한 체지방 축적으로 인해 건강에 위협을 주는 일종의 질병으로 정의될 수 있다. 국제비만전문위원회(International Obesity Task Force, IOTF)의 보고에 의하면 세계인구의 1/4을 차지하는 약 17 억의 인구가 체중을 감량할 필요가 있다고 하여 선진국과 개발도상국 모두에게 심각한 사회문제로 대두되고 있다Obesity can be defined as a type of disease that threatens health due to excessive body fat accumulation. According to a report by the International Obesity Task Force (IOTF), about 1.7 billion people, which account for a quarter of the world's population, need to lose weight, which has emerged as a serious social problem for both developed and developing countries. have
급증하는 생활습관병(성인병)의 30 ~ 60%가 비만에 기인하며 일본의 통계로는 5 Kg 체중을 감소시키는데 의료비가 2조엔 (한화 25조원)이 필요하다는 분석이 나와 있으며, 과체중, 비만의 출현율은 4 ~ 5인당 1명인데 금후에도 증가가 계속될 예상이다. 이런 경향은 미국, 유럽에서는 더욱 심각한 국가적 문제이며, 한국에서도 식생활이 서구화되어 소아비만 출현율이 급격히 증가하고, 생활이 윤택하여 고지방, 고칼로리 식사를 하는 기회는 많아졌으나 운동 부족 등 섭취한 에너지보다 소모하는 에너지가 현저히 작으므로 인해 비만자가 급증하고 있다. 또한, 젊은 여성은 미용효과를 위해, 결혼 후 여성들 또한 체중과다 내지 비만자가 많아 젊었을 때와 같은 몸매를 유지하기 위해 대단히 노력하고 있다.30 to 60% of the rapidly increasing lifestyle-related diseases (adult diseases) are caused by obesity, and according to Japanese statistics, it is analyzed that 2 trillion yen (25 trillion won) is required for medical expenses to lose 5 kg weight, and the incidence of overweight and obesity For every 4-5 people, the number is expected to continue increasing in the future. This trend is a more serious national problem in the United States and Europe, and the incidence of childhood obesity has rapidly increased due to the westernization of dietary habits in Korea, and the chances of eating high-fat, high-calorie meals have increased due to the rich life, but consumed more than energy consumed such as lack of exercise. Because the energy to do is remarkably small, obese people are increasing rapidly. In addition, young women are making great efforts to maintain the same body shape as when they were young because there are many overweight or obese women after marriage.
항비만 소재로는 식욕억제제로 덱스플렌플루라민(Dexflenfluramine), 페닐알라닌(Phenylalanine), 타이로신(Tyrosine)과 메싸이오닌(Methionine), 지방결합제 (흡수억제)로 올리스타트(Orlistat), 키토산, 지방연소제로 실부트라민(Silbutramine), 에페드린(Ephedrine), 카페인과 지실, 가르시니아 캄보지아 과실, L-카르니친, 장기능을 조절하는 식이섬유: 차천자피, 글루코만난 각락토만난, 혈당 안정화 기능을 하는 크롬피콜린산(Chromiumpicolinate) 등이 있다. 그러나, 이들 소재들은 약효가 다소 인정되나, 일시적 체중감소, 신속한 체중손실, 약물들에 의한 심장, 혈압, 신경계에 대한 부작용이 있다.Anti-obesity materials include dexflenfluramine, phenylalanine, tyrosine and methionine as appetite suppressants, as well as fat binding agents (absorption inhibitors), orlistat, chitosan, and fat burning. Zero silbutramine, ephedrine, caffeine and fat, garcinia cambogia fruit, L-carnitine, dietary fiber that regulates intestinal function: tea puncture, glucomannan keratomannan, chromium blood that stabilizes blood sugar Cholic acid (Chromium picolinate) and the like. However, although these materials are somewhat effective, there are side effects on the heart, blood pressure, and nervous system due to temporary weight loss, rapid weight loss, and drugs.
고추(Capsicum annuum)는 열대성 식물로 가지과(Solanaceae)에 속하는 한해살이풀로 분류되며, 전 세계적으로 가장 많이 섭취하고 있는 채소 중 하나이다. 우리나라에서는 주로 늦봄부터 여름에 걸쳐 재배되며, 김치의 주재료로써 오래전부터 식재료로 사용됐다. 현재 전 세계적으로 알려진 고추의 품종은 20~30여종이 있으며, 그중 Capsicum annuum, Capsicum frutescens, Capsicum chinense, Capsicum baccatum, Capsicum pubescens 등이 가장 많이 재배되고 있다. 고추는 비타민과 무기질을 풍부하게 함유하고 있을 뿐만 아니라, carotenoid, quercetin, luteolin 및 capsaicinoids와 같은 페놀성 화합물을 다량 함유하고 있다고 보고되고 있다.Pepper ( Capsicum annuum ) is a tropical plant, classified as an annual plant belonging to the Solanaceae family , and is one of the most consumed vegetables worldwide. In Korea, it is cultivated mainly from late spring to summer, and has been used as a food ingredient for a long time as the main ingredient of kimchi. Currently, there are about 20 to 30 varieties of pepper known worldwide, of which Capsicum annuum, Capsicum frutescens, Capsicum chinense, Capsicum baccatum, and Capsicum pubescens are the most cultivated. Peppers are reported to be rich in vitamins and minerals, as well as high amounts of phenolic compounds such as carotenoid, quercetin, luteolin and capsaicinoids.
이러한 고추의 생리활성으로는 항산화 작용, 지질대사의 항진작용, 감염효과, 체력지속작용, 진통작용, 위산분비항진작용, 항스트레스작용 등 다양한 활성을 나타내는 것으로 알려져 있다(오, 2004; 이와이, 2002). 하지만 고추에 대한 연구는 많이 알려져 있으나 고추 잎에 대한 연구는 미비한 실정이다. 그리고 고추의 일상생활에 활용도는 높으나 고추 잎의 이용도는 나물을 해먹는 정도 밖에 이용도가 낮은 실정이다. 특히 고춧잎을 활용한 비만의 개선, 예방 또는 치료를 효과적으로 개선할 수 있는 조성물에 대해서는 전혀 공지된 바 없다.These physiological activities of pepper are known to exhibit various activities such as antioxidant, lipid metabolism, infection, physical strength, analgesic, gastric acid secretion, and anti-stress (Oh, 2004; Iwai, 2002). ). However, many studies on red pepper are known, but studies on red pepper leaves are insufficient. In addition, the utilization of red pepper in daily life is high, but the utilization of red pepper leaves is low, except for eating herbs. In particular, there is no known composition that can effectively improve the improvement, prevention or treatment of obesity using red pepper leaves.
따라서, 본 발명자들은 천연물로부터 비만 혹은 대사성질환을 효과적으로 개선할 수 있는 새로운 조성물을 개발하고자 예의 노력하였고, 그 결과 본 발명자들은 고춧잎 추출물이 인체에 대해 안정하고 부작용이 없으며, 종래 비만 억제 물질 혹은 대사성질환 치료물질과 동등하거나 그 이상의 효능을 갖는 것을 확인함으로서, 본 발명을 완성하게 되었다.Therefore, the present inventors have made diligent efforts to develop a new composition that can effectively improve obesity or metabolic diseases from natural products, and as a result, the present inventors have made red pepper leaf extract stable for the human body and have no side effects, and conventional obesity inhibitors or metabolic diseases By confirming that it has an efficacy equal to or greater than that of a therapeutic substance, the present invention has been completed.
본 발명의 목적은 고춧잎 추출물을 유효성분으로 하는 비만 혹은 대사성질환 개선 또는 예방용 식품 조성물을 제공하는데 있다.It is an object of the present invention to provide a food composition for improving or preventing obesity or metabolic diseases, using red pepper leaf extract as an active ingredient.
본 발명의 다른 목적은 고춧잎 추출물을 유효성분으로 하는 비만 혹은 대사성질환 예방 또는 치료용 약학 조성물을 제공하는데 있다.Another object of the present invention is to provide a pharmaceutical composition for preventing or treating obesity or metabolic diseases, comprising red pepper leaf extract as an active ingredient.
상기 목적을 달성하기 위하여, 본 발명은 고춧잎 추출물을 유효성분으로 하는 비만 혹은 대사성질환 개선, 또는 예방용 식품 조성물을 제공한다.In order to achieve the above object, the present invention provides a food composition for improving or preventing obesity or metabolic disease, using red pepper leaf extract as an active ingredient.
상기 고춧잎 추출물은 물, 탄소수 1 내지 4개의 알코올 또는 이들의 혼합용매로 추출된 것일 수 있다.The red pepper leaf extract may be extracted with water, alcohol having 1 to 4 carbon atoms, or a mixed solvent thereof.
상기 조성물은 전지방세포 분화와 지방 축적을 억제하며, 체중과 체지방의 증가를 감소시키며, 혈청 내 엔도톡신, 중성지방 및 총 콜레스테롤 농도를 낮추고, 혈청 내 지방분화 관련 호르몬의 발현을 억제하는 것일 수 있다.The composition may be one that inhibits proliferative cell differentiation and fat accumulation, reduces an increase in body weight and body fat, lowers the concentration of endotoxin, triglyceride and total cholesterol in serum, and inhibits the expression of hormones related to fat differentiation in the serum. .
상기 목적을 달성하기 위하여, 본 발명은 고춧잎 추출물을 유효성분으로 하는 비만 혹은 대사성질환 예방 또는 치료용 약학 조성물을 제공한다.In order to achieve the above object, the present invention provides a pharmaceutical composition for preventing or treating obesity or metabolic diseases, using red pepper leaf extract as an active ingredient.
상기 고춧잎 추출물은 물, 탄소수 1 내지 4개의 알코올 또는 이들의 혼합용매로 추출된 것일 수 있다.The red pepper leaf extract may be extracted with water, alcohol having 1 to 4 carbon atoms, or a mixed solvent thereof.
상기 조성물은 전지방세포 분화와 지방 축적을 억제하며, 체중과 체지방의 증가를 감소시키며, 혈청 내 엔도톡신, 중성지방 및 총 콜레스테롤 농도를 낮추고, 혈청 내 지방분화 관련 호르몬의 발현을 억제하는 것일 수 있다.The composition may be one that inhibits proliferative cell differentiation and fat accumulation, reduces an increase in body weight and body fat, lowers the concentration of endotoxin, triglyceride and total cholesterol in serum, and inhibits the expression of hormones related to fat differentiation in the serum. .
본 발명의 조성물은 고춧잎 추출물을 포함하는 것으로써, 상기 조성물은 전지방세포 분화와 지방 축적을 억제하며, 체중과 체지방의 증가를 감소시키며, 혈청 내 엔도톡신, 중성지방 및 총 콜레스테롤 농도를 낮추고, 혈청 내 지방분화 관련 호르몬의 발현을 억제하는 효과를 갖는다. 또한 본 발명에 따른 조성물은 비만 뿐만 아니라 면역 활성도 증진시킴으로써 비만의 치료와 더불어 대사성질환도 예방, 개선 또는 치료할 수 있으므로 비만 혹은 대사성질환 개선, 예방 및 치료를 위한 기능성 식품 및 약제 등에 유용하게 이용될 수 있다.The composition of the present invention comprises a red pepper leaf extract, wherein the composition inhibits proliferative cell differentiation and fat accumulation, reduces an increase in body weight and body fat, lowers endotoxin, triglyceride and total cholesterol concentration in serum, and It has the effect of inhibiting the expression of hormones related to internal fat differentiation. In addition, the composition according to the present invention can be usefully used in functional foods and pharmaceuticals for improving, preventing and treating obesity or metabolic diseases, as well as the treatment of obesity by enhancing immune activity as well as obesity. have.
도 1은 실시예 1로부터 제조된 고춧잎 열수 추출물 및 실시예 2로부터 제조된 고춧잎 고분자 분획물 처리에 의한 3T3-L1 세포내 지질함량 변화를 확인하기 위한 Oil red O 염색결과이다.
도 2는 실시예 1로부터 제조된 고춧잎 열수 추출물 및 실시예 2로부터 제조된 고춧잎 고분자 분획물의 지방세포분화 억제효능을 실험한 결과이다.
도 3은 정상군(NC), 고지방 식이 대조군(HF), 비교예 1의 가르시니아 캄보지아 추출물을 50 mg/kg 투여한 양성 대조군(GC), 실시예 1의 고춧잎 추출물 50 mg/kg 투여군(WEPL50) 및 실시예 1의 고춧잎 추출물 100 mg/kg 투여군(WEPL100)에서의 시간별 체중변화를 나타낸 그래프이다.
도 4는 정상군(NC), 고지방 식이 대조군(HF), 비교예 1의 가르시니아 캄보지아 추출물을 50 mg/kg 투여한 양성 대조군(GC), 실시예 1의 고춧잎 추출물 50 mg/kg 투여군(WEPL50) 및 실시예 1의 고춧잎 추출물 100 mg/kg 투여군(WEPL100)에서 백색 부고환 지방 조직을 적출한 후, 무게를 측정하여 나타낸 그래프이다.
도 5는 정상군(NC), 고지방 식이 대조군(HF), 비교예 1의 가르시니아 캄보지아 추출물을 50 mg/kg 투여한 양성 대조군(GC), 실시예 1의 고춧잎 추출물 50 mg/kg 투여군(WEPL50) 및 실시예 1의 고춧잎 추출물 100 mg/kg 투여군(WEPL100)으로부터 적출한 혈청 내 엔도톡신 농도를 측정하여 나타낸 그래프이다.
도 6은 정상군(NC), 고지방 식이 대조군(HF), 비교예 1의 가르시니아 캄보지아 추출물을 50 mg/kg 투여한 양성 대조군(GC), 실시예 1의 고춧잎 추출물 50 mg/kg 투여군(WEPL50) 및 실시예 1의 고춧잎 추출물 100 mg/kg 투여군(WEPL100)로부터 적출한 혈청 내 중성지방 농도를 측정하여 나타낸 그래프이다.
도 7은 정상군(NC), 고지방 식이 대조군(HF), 비교예 1의 가르시니아 캄보지아 추출물을 50 mg/kg 투여한 양성 대조군(GC), 실시예 1의 고춧잎 추출물 50 mg/kg 투여군(WEPL50) 및 실시예 1의 고춧잎 추출물 100 mg/kg 투여군(WEPL100)로부터 적출한 혈청 내 총 콜레스테롤 농도를 측정하여 나타낸 그래프이다.
도 8은 정상군(NC), 고지방 식이 대조군(HF), 비교예 1의 가르시니아 캄보지아 추출물을 50 mg/kg 투여한 양성 대조군(GC), 실시예 1의 고춧잎 추출물 50 mg/kg 투여군(WEPL50) 및 실시예 1의 고춧잎 추출물 100 mg/kg 투여군(WEPL100)으로부터 적출한 혈청 내 렙틴 농도를 측정하여 나타낸 그래프이다.
도 9는 정상군(NC), 고지방 식이 대조군(HF), 비교예 1의 가르시니아 캄보지아 추출물을 50 mg/kg 투여한 양성 대조군(GC), 실시예 1의 고춧잎 추출물 50 mg/kg 투여군(WEPL50) 및 실시예 1의 고춧잎 추출물 100 mg/kg 투여군(WEPL100)으로부터 적출한 혈청 내 인슐린 농도를 측정하여 나타낸 그래프이다.1 is an Oil red O staining result for confirming the change in lipid content in 3T3-L1 cells by treatment with hot water extract of red pepper leaf prepared from Example 1 and polymer fraction of red pepper leaf prepared from Example 2. FIG.
Figure 2 is a result of testing the effect of inhibiting adipocyte differentiation of the hot water extract of red pepper leaf prepared in Example 1 and the polymer fraction of red pepper leaf prepared in Example 2. FIG.
3 is a normal group (NC), a high-fat diet control (HF), a positive control (GC) in which 50 mg/kg of the garcinia cambogia extract of Comparative Example 1 was administered, and a 50 mg/kg administration group of red pepper leaf extract of Example 1 (WEPL50) And a graph showing the change in body weight over time in the 100 mg/kg administration group (WEPL100) of the red pepper leaf extract of Example 1.
4 is a normal group (NC), a high-fat diet control group (HF), a positive control group (GC) in which 50 mg/kg of garcinia cambogia extract of Comparative Example 1 was administered, and a 50 mg/kg administration group of red pepper leaf extract of Example 1 (WEPL50) And after extracting the white epididymis adipose tissue from the 100 mg/kg administration group (WEPL100) of red pepper leaf extract of Example 1, it is a graph showing the weight measured.
5 is a normal group (NC), a high-fat diet control group (HF), a positive control group (GC) in which 50 mg/kg of garcinia cambogia extract of Comparative Example 1 was administered, and a 50 mg/kg administration group of red pepper leaf extract of Example 1 (WEPL50) And it is a graph showing by measuring the concentration of endotoxin in the serum extracted from the 100 mg / kg administration group (WEPL100) of red pepper leaf extract of Example 1.
6 is a normal group (NC), a high-fat diet control group (HF), a positive control group administered with 50 mg/kg of garcinia cambogia extract of Comparative Example 1 (GC), and a 50 mg/kg administration group of red pepper leaf extract of Example 1 (WEPL50) And a graph showing the concentration of triglycerides in the serum extracted from the 100 mg/kg administration group (WEPL100) of the red pepper leaf extract of Example 1.
7 is a normal group (NC), a high-fat diet control group (HF), a positive control group (GC) in which 50 mg/kg of garcinia cambogia extract of Comparative Example 1 was administered, and a 50 mg/kg administration group of red pepper leaf extract of Example 1 (WEPL50) And it is a graph showing by measuring the total cholesterol concentration in the serum extracted from the 100 mg / kg administration group (WEPL100) of red pepper leaf extract of Example 1.
Figure 8 is a normal group (NC), a high-fat diet control (HF), a positive control (GC) administered with 50 mg/kg of the garcinia cambogia extract of Comparative Example 1, and a 50 mg/kg administration group of red pepper leaf extract of Example 1 (WEPL50) And it is a graph showing by measuring the concentration of leptin in serum extracted from the 100 mg/kg administration group (WEPL100) of the red pepper leaf extract of Example 1.
9 is a normal group (NC), a high-fat diet control group (HF), a positive control group administered with 50 mg/kg of garcinia cambogia extract of Comparative Example 1 (GC), and a 50 mg/kg administration group of red pepper leaf extract of Example 1 (WEPL50) And it is a graph showing by measuring the insulin concentration in the serum extracted from the 100 mg / kg administration group (WEPL100) of red pepper leaf extract of Example 1.
본 발명은 고춧잎 추출물을 유효성분으로 하는 비만 혹은 대사성질환 개선, 예방 또는 치료용 조성물에 관한 것이다.The present invention relates to a composition for improving, preventing or treating obesity or metabolic diseases, using red pepper leaf extract as an active ingredient.
이하, 본 발명을 상세하게 설명한다.Hereinafter, the present invention will be described in detail.
본 발명 고춧잎 추출물을 유효성분으로 하는 비만 혹은 대사성질환 개선, 예방 또는 치료용 조성물에 관한 것이다.The present invention relates to a composition for improving, preventing or treating obesity or metabolic diseases, using red pepper leaf extract as an active ingredient.
고추(Capsicum annuum)는 열대성 식물로 가지과(Solanaceae)에 속하는 한해살이풀로 분류되며, 전 세계적으로 가장 많이 섭취하고 있는 채소 중 하나이다. 우리나라에서는 주로 늦봄부터 여름에 걸쳐 재배되며, 김치의 주재료로써 오래전부터 식재료로 사용됐다. 현재 전 세계적으로 알려진 고추의 품종은 20~30여종이 있으며, 그중 Capsicum annuum, Capsicum frutescens, Capsicum chinense, Capsicum baccatum, Capsicum pubescens 등이 가장 많이 재배되고 있다. 고추는 비타민과 무기질을 풍부하게 함유하고 있을 뿐만 아니라, carotenoid, quercetin, luteolin 및 capsaicinoids와 같은 페놀성 화합물을 다량 함유하고 있다고 보고되고 있으나, 고추 잎에 대한 연구는 미비한 실정이다.Pepper ( Capsicum annuum ) is a tropical plant, classified as an annual plant belonging to the Solanaceae family , and is one of the most consumed vegetables worldwide. In Korea, it is cultivated mainly from late spring to summer, and has been used as a food ingredient for a long time as the main ingredient of kimchi. Currently, there are about 20 to 30 varieties of pepper known worldwide, of which Capsicum annuum, Capsicum frutescens, Capsicum chinense, Capsicum baccatum, and Capsicum pubescens are the most cultivated. Pepper is not only rich in vitamins and minerals, but it has been reported that it contains a large amount of phenolic compounds such as carotenoid, quercetin, luteolin and capsaicinoids, but studies on pepper leaves are insufficient.
본 발명에서 '비만'이란, 단순히 체중이 많이 나가는 것이 아니라 체지방이 과도하게 축적된 상태를 말한다. 겉으로 정상체중으로 보여도 체지방 비율이 높으면 비만이라고 할 수 있다는 의미이다. 보통 비만을 판정하는 방법은 체질량지수 (BMI)를 이용하게 되는데 23~24.9인 경우에 과체중, 25~29.9까지를 경도비만으로 판정하며, 30~34.9는 중등도비만, 35 이상일 경우는 고도비만으로 판정하고 있다. 비만은 한가지 원인보다는 여러 원인이 복합적으로 작용하여 발생하는데, 서구화된 식습관을 포함하여 잘못된 식습관과 활동량 감소, 정서적 요인, 유전적 요인 등을 들 수 있으며 이렇게 발생한 비만은 결국 고지혈증, 당뇨병, 고혈압 등 만성질환의 발생 위험을 높이게 된다. In the present invention, the term'obesity' refers to a state in which body fat is accumulated excessively, rather than simply gaining a lot of weight. It means that even if it looks normal on the outside, if the percentage of body fat is high, it can be called obesity. Normally, the method of determining obesity is to use the body mass index (BMI). In the case of 23 to 24.9, overweight, 25 to 29.9 is determined only with mild obesity, 30 to 34.9 is determined as moderate obesity, and in the case of 35 or more, it is determined as high obesity. Are doing. Obesity is caused by a combination of multiple causes rather than a single cause.Including westernized eating habits, incorrect eating habits, decreased activity levels, emotional factors, and genetic factors can be cited.The resulting obesity eventually leads to chronic hyperlipidemia, diabetes, and high blood pressure. It increases the risk of developing the disease.
본 발명에서 '대사성질환'이란, 비만과 밀접하게 연관성이 있거나, 비만에 기인하는 상태 또는 질환을 의미하며, 구체적으로 지방간, 제2형 당뇨, 고지혈증, 심혈관 질환 및 동맥경화증으로 이루어진 군에서 선택되는 하나 이상일 수 있다. In the present invention, the term'metabolic disease' means a condition or disease that is closely related to or is caused by obesity, and is specifically selected from the group consisting of fatty liver,
본 발명에서 지방간(fatty liver)은 간의 지방대사 장애로 지방이 간세포에 과도한 양으로 축적되는 상태 또는 질환을 의미한다.In the present invention, fatty liver refers to a condition or disease in which fat is accumulated in an excessive amount in liver cells due to a disorder in the fat metabolism of the liver.
본 발명에서 고지혈증은 혈액 중에 지방 성분, 특히 콜레스테롤(cholesterol)과 중성 지방(triglyceride)의 농도가 정상 수치에 비해 높은 상태 또는 질환을 의미하며, 혈액 중의 지질 농도를 저하시키는 것이 요구되는 모든 상태를 포함하는 광범위한 의미로 사용된다.In the present invention, hyperlipidemia refers to a condition or disease in which the concentration of fat components, especially cholesterol and triglyceride in the blood is higher than the normal level, and includes all conditions requiring lowering the lipid concentration in the blood. Is used in a broad sense.
본 명세서에서 동맥경화증(arteriosclerosis)은 동맥벽이 두꺼워지고 탄력성이 감소하여 체내의 장기 및 조직으로의 혈액 순환이 저하되는 상태 또는 질환을 의미하며, 지방, 콜레스테롤 등 기타 물질이 동맥내벽에 침착되어 플라크(plaque)를 형성하여 내강이 좁아짐으로써 혈액 순환이 저하되는 상태 또는 질환을 의미하는 "아테롬성 동맥경화증(atherosclerosis)"을 포함하는 의미를 가진다. 동맥경화증은 체내 어느 부위에서도 발생할 수 있으며, 심장내 혈관에서 발생하는 경우에는 협심증, 심근경색 등 관상동맥질환이 유발되며, 뇌에서 발생하는 뇌경색이 유발될 수 있으며, 신장에서 일어나는 경우에는 신부전증 등이 유발될 수 있다.In the present specification, arteriosclerosis refers to a condition or disease in which blood circulation to organs and tissues in the body decreases due to thickening of the arterial wall and decreasing elasticity, and other substances such as fat and cholesterol are deposited on the inner wall of the artery and thus plaque ( Plaque) is formed to narrow the lumen, thereby reducing blood circulation, which means a condition or disease in which "atherosclerosis" is included. Arteriosclerosis can occur anywhere in the body, and if it occurs in the blood vessels in the heart, coronary artery disease such as angina pectoris and myocardial infarction can be caused, and cerebral infarction that occurs in the brain can be caused. Can be triggered.
구체적으로 상기 비만 혹은 대사성질환 개선, 예방 또는 치료용 조성물은 상기 다양한 원인에 의해 체중 또는 체지방이 증가되거나, 대사성 질환이 야기되는 것을, 개선, 예방, 완화, 억제 및 치료하는 조성물이라고도 할 수 있다. 보다 바람직하게 고지방 식에 의해 유발된 비만 혹은 대사성질환을 개선, 예방, 치료하는 효과를 갖는다. Specifically, the composition for improving, preventing or treating obesity or metabolic disease may be referred to as a composition for improving, preventing, alleviating, suppressing, and treating weight or body fat increase or metabolic disease caused by the various causes. More preferably, it has the effect of improving, preventing, and treating obesity or metabolic diseases caused by a high fat diet.
본 발명의 실험결과에 의하면, 고지방 식이를 장기간 투여하였을 때, 체중과 체지방이 증가하였음을 볼 수 있다. 이는 시간이 경과함에 따라 지방세포의 분화와 지방 축적을 유도하고, 체중과 체지방의 함량을 증가시키며, 혈청 내 엔도톡신, 중성지방 및 총 콜레스테롤 농도뿐만 아니라 지방분화 관련 호르몬의 발현을 높여, 비만 혹은 대사성질환을 유도하게 된다.According to the experimental results of the present invention, it can be seen that weight and body fat increased when a high fat diet was administered for a long time. It induces the differentiation of adipocytes and fat accumulation over time, increases the content of body weight and body fat, and increases the expression of hormones related to fat differentiation as well as endotoxin, triglyceride, and total cholesterol concentrations in the serum. Induce disease.
이때, 고춧잎 추출물을 병용투여하면 전지방세포 분화와 지방 축적을 억제하며, 체중과 체지방의 증가를 감소시키며, 혈청 내 엔도톡신, 중성지방 및 총 콜레스테롤 농도를 낮추고, 혈청 내 지방분화 관련 호르몬의 발현을 억제하는 것을 확인할 수 있다. 따라서 본 발명에 따른 고춧잎 추출물을 유효성분으로 하는 조성물은 비만 혹은 대사성질환 개선, 예방 또는 치료 효과를 가짐을 알 수 있다.At this time, when the red pepper leaf extract is administered together, it suppresses the differentiation of fat cells and the accumulation of fat, reduces the increase in body weight and body fat, lowers the concentration of endotoxin, triglyceride and total cholesterol in the serum, and increases the expression of hormones related to fat differentiation in the serum. It can be confirmed that it suppresses. Therefore, it can be seen that the composition comprising the red pepper leaf extract according to the present invention as an active ingredient has an effect of improving, preventing or treating obesity or metabolic diseases.
본 발명에서 '추출물'은 추출 원재료에 추출 용매를 처리하여 얻은 조추출물뿐만 아니라 조추출물의 가공물도 포함한다. 예를 들어, 고춧잎 추출물은 감압 증류 및 동결 건조 또는 분무 건조 등과 같은 추가적인 과정에 의해 분말 상태로 제조될 수 있다. In the present invention, the'extract' includes not only the crude extract obtained by treating the extraction raw material with the extraction solvent, but also the processed product of the crude extract. For example, the red pepper leaf extract may be prepared in a powder state by additional processes such as distillation under reduced pressure and freeze drying or spray drying.
또한 본 발명에서 '추출물'은 상기 조추출물을 추가적으로 분획(fractionation)한 분획물도 포함한다. 즉, 고춧잎 추출물은 추출 용매를 이용하여 얻은 것뿐만 아니라, 여기에 정제과정을 추가적으로 적용하여 얻은 것도 포함한다. 예를 들어, 일정한 분자량 컷-오프 값을 갖는 한외 여과막을 통과시켜 얻은 고분자 분획물, 다양한 크로마토그래피(크기, 전하, 소수성 또는 친화성에 따른 분리를 위해 제작된 것)에 의한 분리 등, 추가적으로 실시된 다양한 방법을 통해 정제할 수 있다.In addition, the'extract' in the present invention also includes a fraction obtained by further fractionating the crude extract. That is, the red pepper leaf extract includes not only those obtained using an extraction solvent, but also those obtained by additionally applying a purification process thereto. For example, a polymer fraction obtained by passing through an ultrafiltration membrane having a certain molecular weight cut-off value, separation by various chromatography (made for separation according to size, charge, hydrophobicity or affinity), etc. It can be purified through a method.
상기 고분자 분획물은 바람직하게 고춧잎 추출물 또는 고춧잎 추출물을 추출 용매를 이용해 얻은 후, 분자량 10 kDa 이상의 고분자 물질만 분리해 놓은 분획물일 수 있다.The polymer fraction may be a fraction obtained by separating only a polymer material having a molecular weight of 10 kDa or more after obtaining a red pepper leaf extract or a red pepper leaf extract using an extraction solvent.
또한 본 발명에서 '고춧잎 추출물'은 상기 고추 잎을 물, 탄소수 1 내지 4 개의 알코올 또는 이들의 혼합 용매에 의한 추출물로서, 추출방법은 특별히 한정할 필요가 없다. 바람직하게는 상기 고춧잎 추출물은 고춧잎 열수 추출물 또는 고춧잎 에탄올 수용액일 수 있으며, 예를 들어 고춧잎 주정 추출물일 수 있다. 가장 바람직하게는 고춧잎 열수 추출물일 수 있다.In addition, in the present invention, the'pepper leaf extract' is an extract of the red pepper leaf using water, alcohol having 1 to 4 carbon atoms, or a mixed solvent thereof, and the extraction method does not need to be particularly limited. Preferably, the red pepper leaf extract may be a hot water extract of red pepper leaf or an ethanol solution of red pepper leaf, and may be, for example, a red pepper leaf alcohol extract. Most preferably, it may be a hot water extract of red pepper leaves.
또한, 상기 고춧잎 추출물은 상기 고춧잎 추출물을 가공하고, 이를 다시 물, 탄소수 1 내지 4 개의 알코올 또는 이들의 혼합 용매로 1회 이상 반복 추출한 것일 수 있다.In addition, the red pepper leaf extract may be processed by the red pepper leaf extract, and then repeatedly extracted one or more times with water, alcohol having 1 to 4 carbon atoms, or a mixed solvent thereof.
상기 고춧잎은 고추의 잎을 일정한 크기로 절단하여 그늘이나, 건조기를 사용하여 건조한 후, 파쇄시키거나 그대로 사용할 수 있다. 상기 건조 기간은 상기 고춧잎 내에 수분함량이 20% 미만인 것이라면 특별히 한정되지 않는다.The red pepper leaves may be cut into a certain size, dried using a shade or a dryer, and then crushed or used as it is. The drying period is not particularly limited as long as the moisture content in the red pepper leaves is less than 20%.
고추의 다른 부위에 비해 고추 잎을 사용한 것이, 고지방 식이를 장기간 투여하였을 때 전지방세포 분화와 지방 축적을 억제하고, 체중과 체지방의 증가를 감소시키며, 혈청 내 엔도톡신, 중성지방 및 총 콜레스테롤 농도를 낮추고, 혈청 내 지방분화 관련 호르몬의 발현을 억제함에 있어서 1.5~2.5배 더 우수하므로, 고추의 다른 부위에 비해 고춧잎 추출물은 비만 혹은 대사성질환을 예방 또는 개선 또는 치료하는 효과가 현저히 우수하다.Compared to other parts of red pepper, red pepper leaves are used to inhibit proliferative cell differentiation and fat accumulation, reduce weight and body fat gain, and reduce serum endotoxin, triglyceride, and total cholesterol concentrations when a high fat diet is administered for a long time. Since it is 1.5 to 2.5 times better in lowering and inhibiting the expression of hormones related to fat differentiation in the serum, red pepper leaf extract is remarkably excellent in preventing, improving or treating obesity or metabolic diseases compared to other parts of pepper.
본 발명에서 '유효성분으로 하는' 또는 '유효성분으로 포함하는'이란 본 발명의 고춧잎 추출물의 비만 혹은 대사성질환을 개선, 예방 또는 치료하는 데 충분한 양을 포함하는 것을 의미한다. 상기 고춧잎 추출물은 천연물로서 과량 투여하여도 인체에 부작용이 없으므로 본 발명의 조성물 내에 포함되는 고춧잎 추출물의 양적 상한 및 하한은 당업자가 적절한 범위 내에서 선택하여 실시할 수 있다.In the present invention, "containing as an active ingredient" or "including as an active ingredient" means including an amount sufficient to improve, prevent or treat obesity or metabolic diseases of the red pepper leaf extract of the present invention. Since the red pepper leaf extract is a natural product and does not have side effects on the human body even if it is administered in an excessive amount, the upper and lower limits of the quantity of the red pepper leaf extract included in the composition of the present invention can be selected and carried out by a person skilled in the art within an appropriate range.
본 발명의 조성물은 식품 조성물로, 본 발명의 고춧잎 추출물을 유효성분으로 하는 비만 혹은 대사성질환 개선, 예방용 식품 조성물로 다양하게 이용될 수 있다. 본 발명의 고춧잎 추출물을 유효성분으로 포함하는 후술하는 하기 약학 조성물과 동일한 방식으로 제제화되어 기능성 식품으로 이용하거나, 각종 식품에 첨가할 수 있다. 본 발명의 조성물을 첨가할 수 있는 식품으로는 예를 들어, 음료류, 알코올 음료류, 과자류, 다이어트바, 유제품, 육류, 초코렛, 피자, 라면, 기타 면류, 껌류, 아이스크림류, 비타민 복합제, 건강보조식품류 등이 있다.The composition of the present invention may be variously used as a food composition for improving and preventing obesity or metabolic diseases using the red pepper leaf extract of the present invention as an active ingredient. Formulated in the same manner as the pharmaceutical composition described below containing the red pepper leaf extract of the present invention as an active ingredient, it can be used as a functional food or added to various foods. Foods to which the composition of the present invention can be added include, for example, beverages, alcoholic beverages, confectionery, diet bars, dairy products, meat, chocolate, pizza, ramen, other noodles, gum, ice cream, vitamin complexes, health supplements. Etc.
본 발명의 식품 조성물은 유효성분으로서 고춧잎 추출물뿐만 아니라, 식품 제조 시에 통상적으로 첨가되는 성분을 포함할 수 있으며, 예를 들어, 단백질, 탄수화물, 지방, 영양소, 조미제 및 향미제를 포함한다. 상술한 탄수화물의 예는 모노사카라이드, 예를 들어, 포도당, 과당 등; 디사카라이드, 예를 들어 말토스, 슈크로스, 올리고당 등; 및 폴리사카라이드, 예를 들어 덱스트린, 사이클로덱스트린 등과 같은 통상적인 당 및 자일리톨, 소르비톨, 에리트리톨 등의 당알콜이다. 향미제로서 천연 향미제 [타우마틴, 스테비아 추출물(예를 들어 레바우디오시드 A, 글리시르히진 등]) 및 합성 향미제(사카린, 아스파르탐 등)를 사용할 수 있다. 예컨대, 본 발명의 식품 조성물이 드링크제와 음료류로 제조되는 경우에는 본 발명의 고춧잎 추출물 이외에 구연산, 액상과당, 설탕, 포도당, 초산, 사과산, 과즙, 및 각종 식물 추출액 등을 추가로 포함시킬 수 있다.The food composition of the present invention may include not only red pepper leaf extract as an active ingredient, but also ingredients that are commonly added during food production, and include, for example, proteins, carbohydrates, fats, nutrients, flavoring agents, and flavoring agents. Examples of the aforementioned carbohydrates include monosaccharides such as glucose, fructose, and the like; Disaccharides such as maltose, sucrose, oligosaccharides, and the like; And polysaccharides, for example, common sugars such as dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol. As the flavoring agent, natural flavoring agents [taumatin, stevia extract (eg, rebaudioside A, glycyrrhizin, etc.]) and synthetic flavoring agents (saccharin, aspartame, etc.) can be used. For example, when the food composition of the present invention is made of drinks and beverages, citric acid, liquid fructose, sugar, glucose, acetic acid, malic acid, fruit juice, and various plant extracts, in addition to the red pepper leaf extract of the present invention, may be further included.
본 발명은 상기 고춧잎 추출물을 유효성분으로 포함하는 비만 혹은 대사성질환 개선, 억제 또는 예방용 식품 조성물을 포함하는 건강기능식품을 제공한다. 건강기능식품이란, 고춧잎 추출물을 음료, 차류, 향신료, 껌, 과자류 등의 식품소재에 첨가하거나, 캡슐화, 분말화, 현탁액 등으로 제조한 식품으로, 이를 섭취할 경우 건강상 특정한 효과를 가져오는 것을 의미하나, 일반 약품과는 달리 식품을 원료로 하여 약품의 장기 복용시 발생할 수 있는 부작용 등이 없는 장점이 있다. 이와 같이 하여 얻어지는 본 발명의 건강기능식품은, 일상적으로 섭취하는 것이 가능하기 때문에 매우 유용하다. 이와 같은 건강기능식품에 있어서의 고춧잎 추출물의 첨가량은, 대상인 건강기능식품의 종류에 따라 달라 일률적으로 규정할 수 없지만, 식품 본래의 맛을 손상시키지 않는 범위에서 첨가하면 되며, 대상 식품에 대하여 통상 0.01 내지 50 중량%, 바람직하기로는 0.1 내지 20 중량%의 범위이다. 또한, 환제, 과립제, 정제 또는 캡슐제 형태의 건강기능식품의 경우에는 통상 0.1 내지 100 중량% 바람직하기로는 0.5 내지 80 중량%의 범위에서 첨가하면 된다. 한 구체예에서, 본 발명의 건강기능식품은 환제, 정제, 캡슐제 또는 음료의 형태일 수 있다.The present invention provides a health functional food comprising a food composition for improving, suppressing or preventing obesity or metabolic disease, comprising the red pepper leaf extract as an active ingredient. Health functional foods are foods prepared by adding red pepper leaf extract to food materials such as beverages, teas, spices, chewing gums, confectionery, or encapsulating, powdering, or suspending them. However, unlike general drugs, it has the advantage of not having side effects that may occur when taking drugs for a long time by using food as a raw material. The health functional food of the present invention obtained in this way is very useful because it can be consumed on a daily basis. The amount of red pepper leaf extract added in such health functional foods cannot be uniformly regulated depending on the type of health functional food to be targeted, but can be added within the range that does not damage the original taste of the food. To 50% by weight, preferably 0.1 to 20% by weight. In addition, in the case of health functional foods in the form of pills, granules, tablets or capsules, it is usually added in the range of 0.1 to 100% by weight, preferably 0.5 to 80% by weight. In one embodiment, the health functional food of the present invention may be in the form of a pill, tablet, capsule or beverage.
또 다른 예에서 상기한 바와 같이 고춧잎 추출물을 유효성분으로 하는 비만 혹은 대사성질환 예방 또는 치료용 약학 조성물로 이용될 수 있다. 유효성분인 고춧잎 추출물 외에 약제학적으로 적합하고 생리학적으로 허용되는 보조제를 사용하여 제조될 수 있으며, 상기 보조제로는 부형제, 붕해제, 감미제, 결합제, 피복제, 팽창제, 윤활제, 활택제 또는 향미제 등을 사용할 수 있다.In another example, as described above, it may be used as a pharmaceutical composition for preventing or treating obesity or metabolic diseases using red pepper leaf extract as an active ingredient. In addition to the red pepper leaf extract, which is an active ingredient, it can be prepared using a pharmaceutically suitable and physiologically acceptable auxiliary agent, and the auxiliary agent includes excipients, disintegrants, sweeteners, binders, coating agents, expanding agents, lubricants, lubricants or flavoring agents. Etc. can be used.
상기 약학 조성물은 투여를 위해서 상기 기재한 유효 성분 이외에 추가로 약제학적으로 허용 가능한 담체를 1종 이상 포함하여 약학 조성물로 바람직하게 제제화할 수 있다.For administration, the pharmaceutical composition may include one or more pharmaceutically acceptable carriers in addition to the above-described active ingredients, and may be preferably formulated into a pharmaceutical composition.
상기 약학 조성물의 제제 형태는 과립제, 산제, 정제, 피복정, 캡슐제, 좌제, 액제, 시럽, 즙, 현탁제, 유제, 점적제 또는 주사 가능한 액제 등이 될 수 있다. 예를 들어, 정제 또는 캡슐제의 형태로의 제제화를 위해, 유효성분은 에탄올, 글리세롤, 물 등과 같은 경구, 무독성의 약제학적으로 허용 가능한 불활성 담체와 결합될 수 있다. 또한, 원하거나 필요한 경우, 적합한 결합제, 윤활제, 붕해제 및 발색제 또한 혼합물로 포함될 수 있다. 적합한 결합제는 이에 제한되는 것은 아니나, 녹말, 젤라틴, 글루코스 또는 베타-락토오스와 같은 천연 당, 옥수수 감미제, 아카시아, 트래커캔스 또는 소듐올레이트와 같은 천연 및 합성 검, 소듐 스테아레이트, 마그네슘 스테아레이트, 소듐 벤조에이트, 소듐 아세테이트, 소듐 클로라이드 등을 포함한다. 붕해제는 이에 제한되는 것은 아니나, 녹말, 메틸 셀룰로스, 아가, 벤토니트, 잔탄 검 등을 포함한다.The formulation form of the pharmaceutical composition may be granules, powders, tablets, coated tablets, capsules, suppositories, solutions, syrups, juices, suspensions, emulsions, drops, or injectable solutions. For example, for formulation in the form of tablets or capsules, the active ingredient may be combined with an oral, non-toxic pharmaceutically acceptable inert carrier such as ethanol, glycerol, water, and the like. In addition, if desired or necessary, suitable binders, lubricants, disintegrants and coloring agents may also be included in the mixture. Suitable binders are, but are not limited to, natural sugars such as starch, gelatin, glucose or beta-lactose, corn sweeteners, natural and synthetic gums such as acacia, lacquercanth or sodium oleate, sodium stearate, magnesium stearate, sodium Benzoate, sodium acetate, sodium chloride, and the like. Disintegrants include, but are not limited to, starch, methyl cellulose, agar, bentonite, xanthan gum, and the like.
액상 용액으로 제제화되는 조성물에 있어서 허용 가능한 약제학적 담체로는, 멸균 및 생체에 적합한 것으로서, 식염수, 멸균수, 링거액, 완충 식염수, 알부민 주사용액, 덱스트로즈 용액, 말토 덱스트린 용액, 글리세롤, 에탄올 및 이들 성분 중 1 성분 이상을 혼합하여 사용할 수 있으며, 필요에 따라 항산화제, 완충액, 정균제 등 다른 통상의 첨가제를 첨가할 수 있다. 또한 희석제, 분산제, 계면활성제, 결합제 및 윤활제를 부가적으로 첨가하여 수용액, 현탁액, 유탁액 등과 같은 주사용 제형, 환약, 캡슐, 과립 또는 정제로 제제화할 수 있다.As acceptable pharmaceutical carriers for compositions formulated as liquid solutions, sterilization and biocompatible, saline, sterile water, Ringer's solution, buffered saline, albumin injection solution, dextrose solution, maltodextrin solution, glycerol, ethanol, and One or more of these components may be mixed and used, and other conventional additives such as antioxidants, buffers, and bacteriostatic agents may be added as necessary. In addition, diluents, dispersants, surfactants, binders, and lubricants may be additionally added to prepare injectable formulations such as aqueous solutions, suspensions, emulsions, etc., pills, capsules, granules, or tablets.
더 나아가 해당분야의 적절한 방법으로 Remington's Pharmaceutical Science, Mack Publishing Company, Easton PA에 개시되어 있는 방법을 이용하여 각 질환에 따라 또는 성분에 따라 바람직하게 제제화할 수 있다.Furthermore, it can be preferably formulated according to each disease or ingredient using a method disclosed in Remington's Pharmaceutical Science, Mack Publishing Company, Easton PA as an appropriate method in the field.
본 발명의 약학 조성물은 경구 또는 비경구로 투여할 수 있고, 비경구 투여인 경우에는 정맥내 주입, 피하 주입, 근육 주입, 복강 주입, 경피 투여 등으로 투여할 수 있으며, 바람직하게는 경구 투여이다.The pharmaceutical composition of the present invention may be administered orally or parenterally, and in the case of parenteral administration, it may be administered by intravenous injection, subcutaneous injection, intramuscular injection, intraperitoneal injection, transdermal administration, and the like, preferably oral administration.
본 발명의 약학 조성물의 적합한 투여량은 제제화 방법, 투여 방식, 환자의 연령, 체중, 성, 병적 상태, 음식, 투여 시간, 투여 경로, 배설 속도 및 반응 감응성과 같은 요인들에 의해 다양하며, 보통으로 숙련된 의사는 소망하는 치료 또는 예방에 효과적인 투여량을 용이하게 결정 및 처방할 수 있다. 본 발명의 바람직한 구현예에 따르면, 본 발명의 약학 조성물의 1일 투여량은 0.001-10 g/㎏이며, 보다 바람직하게는 0.1 g/kg 내지 10 g/kg의 용량으로 투여되는 것일 수 있다.A suitable dosage of the pharmaceutical composition of the present invention varies depending on factors such as formulation method, mode of administration, age, body weight, sex, pathological condition, food, administration time, route of administration, excretion rate and response sensitivity of the patient, and is usually As such, a skilled physician can easily determine and prescribe an effective dosage for the desired treatment or prophylaxis. According to a preferred embodiment of the present invention, the daily dosage of the pharmaceutical composition of the present invention is 0.001-10 g/kg, more preferably 0.1 g/kg to 10 g/kg.
본 발명의 약학 조성물은 약제학적으로 허용되는 담체 및/또는 부형제를 이용하여 제제화함으로써 단위 용량 형태로 제조되거나 또는 다용량 용기 내에 내입시켜 제조될 수 있다. 이때 제형은 오일 또는 수성 매질중의 용액, 현탁액 또는 유화액 형태이거나 엑스제, 분말제, 과립제, 정제 또는 캅셀제 형태일 수도 있으며, 분산제 또는 안정화제를 추가적으로 포함할 수 있다.The pharmaceutical composition of the present invention may be prepared in a unit dosage form by formulation using a pharmaceutically acceptable carrier and/or excipient, or may be prepared by placing it in a multi-dose container. At this time, the formulation may be in the form of a solution, suspension, or emulsion in an oil or aqueous medium, or may be in the form of an extract, powder, granule, tablet or capsule, and may additionally include a dispersant or a stabilizer.
또한, 본 발명은 포유동물에게 유효량의 고춧잎 추출물을 투여하는 것을 포함하는 비만 혹은 대사성질환의 개선, 예방 또는 치료 방법을 제공한다.In addition, the present invention provides a method for improving, preventing or treating obesity or metabolic diseases, comprising administering an effective amount of red pepper leaf extract to a mammal.
여기에서 사용된 용어 "포유동물"은 치료, 관찰 또는 실험의 대상인 포유동물을 말하며, 바람직하게는 인간을 말한다.The term "mammal" as used herein refers to a mammal that is the subject of treatment, observation or experimentation, and preferably refers to a human.
여기에서 사용된 용어 "유효량"은 연구자, 수의사, 의사 또는 기타 임상의에 의해 생각되는 조직계, 동물 또는 인간에서 생물학적 또는 의학적 반응을 유도하는 유효 성분 또는 약학 조성물의 양을 의미하는 것으로, 이는 해당 증상의 완화를 유도하는 양을 포함한다. 본 발명의 유효 성분에 대한 유효량 및 투여횟수는 원하는 효과에 따라 변화될 수 있다. 그러므로, 투여될 최적의 투여량은 당업자에 의해 쉽게 결정될 수 있으며, 체중, 체지방, 혈청 내 중성지방과 콜레스테롤 또는 비만 혹은 대사성질환정도, 조성물에 함유된 유효성분 및 다른 성분의 함량, 제형의 종류, 및 환자의 연령, 체중, 일반 건강 상태, 성별 및 식이, 투여 시간, 투여 경로 및 조성물의 분비율, 치료기간, 동시 사용되는 약물을 비롯한 다양한 인자에 따라 조절될 수 있다. 본 발명의 예방, 치료 또는 개선 방법에 있어서, 성인의 경우, 고춧잎 추출물을 1일 1회 내지 수회 투여시, 0.001 g/㎏ 내지 10 g/㎏의 용량으로 투여하는 것이 바람직하고, 보다 바람직하게는 0.1 g/kg 내지 10 g/kg의 용량으로 투여되는 것일 수 있다.The term "effective amount" as used herein refers to an amount of an active ingredient or pharmaceutical composition that induces a biological or medical response in a tissue system, animal or human, which is considered by a researcher, veterinarian, doctor or other clinician, which Contains an amount that induces relief of the. The effective amount and the number of administrations for the active ingredient of the present invention may vary depending on the desired effect. Therefore, the optimal dosage to be administered can be easily determined by a person skilled in the art, and the weight, body fat, triglyceride and cholesterol in the serum or the degree of obesity or metabolic disease, the content of active ingredients and other ingredients contained in the composition, the type of formulation, And the patient's age, weight, general health status, sex and diet, administration time, administration route and secretion rate of the composition, treatment period, and drugs used simultaneously. In the prevention, treatment or improvement method of the present invention, in the case of an adult, when the red pepper leaf extract is administered once to several times a day, it is preferable to administer it in a dose of 0.001 g/kg to 10 g/kg, and more preferably It may be administered in a dose of 0.1 g / kg to 10 g / kg.
본 발명의 치료방법에서 고춧잎 추출물을 유효성분으로 포함하는 조성물은 경구, 직장, 정맥내, 동맥내, 복강내, 근육내, 흉골내, 경피, 국소, 안구내 또는 피내 경로를 통해 통상적인 방식으로 투여할 수 있고, 바람직하는 경구, 복강 내에 투여할 수 있다.In the treatment method of the present invention, the composition comprising the red pepper leaf extract as an active ingredient is in a conventional manner through oral, rectal, intravenous, intraarterial, intraperitoneal, intramuscular, intrasternal, transdermal, topical, intraocular or intradermal routes. It can be administered, and can be preferably administered orally or intraperitoneally.
이하, 본 발명의 이해를 돕기 위하여 바람직한 실시예를 제시하나, 하기 실시예는 본 발명을 예시하는 것일 뿐 본 발명의 범주 및 기술사상 범위 내에서 다양한 변경 및 수정이 가능함은 당업자에게 있어서 명백한 것이며, 이러한 변형 및 수정이 첨부된 특허청구범위에 속하는 것도 당연한 것이다.Hereinafter, a preferred embodiment is presented to aid the understanding of the present invention, but the following examples are only illustrative of the present invention, and it is obvious to those skilled in the art that various changes and modifications are possible within the scope and spirit of the present invention, It is natural that such modifications and modifications fall within the appended claims.
실시예 1. 고춧잎 열수 추출물Example 1. Hot water extract of red pepper leaves
경북예천농협에서 생산한 국내산 건조 고춧잎을 구매하여 사용하였다. 고춧잎을 50 ℃ 건조 오븐에서 24시간 건조한 다음 분쇄기로 1.0 ㎜ 이하가 되도록 분쇄하여 고춧잎 분말을 준비하였다.Dried domestic red pepper leaves produced by Yecheon Nonghyup in Gyeongbuk were purchased and used. Red pepper leaves were dried in a drying oven at 50° C. for 24 hours and then pulverized to a size of 1.0 mm or less with a grinder to prepare red pepper leaf powder.
고춧잎 분말 5 g에 20 배 부피에 해당하는 증류수를 가하고 80 ℃ 에서 3 시간 동안 환류 추출하여 열수 추출물을 수득하였다. 상기 열수 추출물을 여과한 후, 회전 진공 증발기(rotary vacuum evaporator)를 이용하여 감압농축하고, 72 시간 동안 동결건조하였다. 상기 방법으로 수득한 고춧잎 열수 추출물은 WEPL(Water-soluble extract from pepper leaves)로 기재하였다.Distilled water equivalent to 20 times the volume was added to 5 g of red pepper leaf powder, followed by reflux extraction at 80° C. for 3 hours to obtain a hot water extract. After filtering the hot water extract, it was concentrated under reduced pressure using a rotary vacuum evaporator, and lyophilized for 72 hours. The hot water extract of pepper leaves obtained by the above method was described as WEPL (Water-soluble extract from pepper leaves).
실시예 2. 고춧잎 고분자 분획물Example 2. Red pepper leaf polymer fraction
경북예천농협에서 생산한 국내산 건조 고춧잎을 구매하여 사용하였다. 고춧잎을 50 ℃ 건조 오븐에서 24시간 건조한 다음 분쇄기로 1.0 ㎜ 이하가 되도록 분쇄하여 고춧잎 분말을 준비하였다.Dried domestic red pepper leaves produced by Yecheon Nonghyup in Gyeongbuk were purchased and used. Red pepper leaves were dried in a drying oven at 50° C. for 24 hours and then pulverized to a size of 1.0 mm or less with a grinder to prepare red pepper leaf powder.
고춧잎 분말 100 g에 20 배 부피에 해당하는 증류수를 가하고 80 ℃의 온도에서 3 시간 동안 환류 추출하여 열수 추출물을 수득하였다. 상기 열수 추출물을 여과한 다음, 회전 진공 증발기(rotary vacuum evaporator)를 이용하여 추출액의 1/10이 되도록 감압농축하고, 감압농축된 열수 추출물의 4배 부피(v/v)에 해당하는 80% 주정을 상기 열수 추출물에 가하여 24시간 침전시켰다. 이를 원심분리(6000 rpm, 635 ×g, 30분)하여 침전물을 얻었으며 여기에 소량의 증류수를 가하여 침전물을 재용해하고 투석막(MW cut off 12,000, Sigma-Aldrich Co., St. Louis, MO, USA)을 이용하여 2~3일간 투석을 행하여 저분자물질을 제거하였으며 72 시간 동결건조하여, 고춧잎 고분자 분획물을 얻었다. 상기 방법으로 수득한 고춧잎 고분자 분획물은 HFPL(High-molecular fraction from pepper leaves)라고 명명하였다.Distilled water corresponding to 20 times the volume was added to 100 g of red pepper leaf powder, followed by reflux extraction at 80° C. for 3 hours to obtain a hot water extract. After filtering the hot water extract, it is concentrated under reduced pressure to be 1/10 of the extract using a rotary vacuum evaporator, and 80% alcohol corresponding to 4 times the volume (v/v) of the hot water extract concentrated under reduced pressure Was added to the hot water extract and precipitated for 24 hours. This was centrifuged (6000 rpm, 635 × g, 30 minutes) to obtain a precipitate, and a small amount of distilled water was added thereto to redissolve the precipitate and a dialysis membrane (MW cut off 12,000, Sigma-Aldrich Co., St. Louis, MO, USA) was performed for 2 to 3 days to remove low molecular weight substances, and freeze-dried for 72 hours to obtain a polymer fraction of red pepper leaves. The red pepper leaf polymer fraction obtained by the above method was named HFPL (High-molecular fraction from pepper leaves).
비교예 1. 가르시니아 캄보지아 추출물Comparative Example 1. Garcinia cambogia extract
가르시니아 캄보지아 추출물은 인도 Unicon Natural Products PVT사로부터 구매하여 사용하였다. 이때, 상기 가르시니아 캄보지아 추출물은 HCA을 600 mg/g 이상으로 함유하는 것을 사용하였다.Garcinia cambogia extract was purchased and used from Unicon Natural Products PVT, India. At this time, the garcinia cambogia extract was used that contains 600 mg/g or more of HCA.
<시험예><Test Example>
시험예 1. 실시예 1의 고춧잎 열수 추출물 및 실시예 2의 고춧잎 고분자 분획물의 수율, 당과 단백질 함량 분석Test Example 1. Analysis of yield, sugar and protein content of hot water extract of red pepper leaf of Example 1 and polymer fraction of red pepper leaf of Example 2
중성당 분석은 Albersheim 등의 방법을 일부 변형하여 가수분해 후 각 구성당을 알디톨 아세테이트(alditol acetate)와 aldonolactone로 유도체화 하여 GC(Gas Chromatography ACME-6100, Young-Lin Co. Ltd. Anyang, Korea)를 이용하여 분석하였다. 실시예 1 또는 실시예 2의 시료를 2 M TFA(trifluroacetic acid) 중에서 121℃, 1.5 hr 반응시켜 가수분해한 후, 1 ㎖의 1 M NH4OH (ammonia solution)에 용해하여 10 ㎎의 NaBH4로 4 hr 환원시켰다. Acetic acid를 적당량 가하여 잔존 NaBH4를 제거한 후, 메탄올을 가하며 반복 건조함으로써 과량으로 가해진 아세트산을 제거하여 알디톨(alditol)로 전환하였다. 상기 알디톨(alditol)에 1 ㎖의 아세트산 무수물(acetic anhydride)을 가하여 121℃에서 30 min 동안 반응시켜 알디톨 아세테이트(alditol acetate)로 전환시켰으며 이를 클로로포름/H2O 2상 용매계로 분리하여 추출하고, 추출물은 건조 후 소량의 아세톤에 용해하여 GC 분석용 시료로 사용하였다.For the analysis of neutral sugars, the method of Albersheim et al. was partially modified to derivatize each constituent sugar with alditol acetate and aldonolactone after hydrolysis, and GC (Gas Chromatography ACME-6100, Young-Lin Co. Ltd. Anyang, Korea) ) Was used. The sample of Example 1 or 2 was hydrolyzed by reacting for 1.5 hr at 121° C. in 2 M TFA (trifluroacetic acid), and then dissolved in 1 ml of 1 M NH 4 OH (ammonia solution) and 10 mg of NaBH 4 It was reduced by 4 hr. After adding an appropriate amount of acetic acid to remove the remaining NaBH 4 , methanol was added thereto and repeated drying to remove excess acetic acid and converted to alditol. 1 ml of acetic anhydride was added to the alditol and reacted at 121° C. for 30 min to convert to alditol acetate, which was separated and extracted with a chloroform/H 2 O two-phase solvent system. And, the extract was dried and dissolved in a small amount of acetone to be used as a sample for GC analysis.
단백질 정량은 Bradford법에 따라 측정하였으며, BSA(Bovine Serum Albumin, sigma aldrich)를 표준품으로 사용하여 1 ㎎/㎖를 최고 농도로 하여 일정배수로 희석하였다. Bradford시약 980 ㎕에 표준품과 시료를 각각 20 ㎕를 가하여 반응시킨 후 microplate reader를 이용하여 595 nm에서 흡광도를 측정하였다. 단백질 정량은 BSA에 대한 양으로 환산하였다.Protein quantification was measured according to the Bradford method, and BSA (Bovine Serum Albumin, sigma aldrich) was used as a standard and diluted at a constant multiple with 1 mg/ml as the highest concentration. After adding 20 µl of each standard and sample to 980 µl of Bradford reagent, the absorbance was measured at 595 nm using a microplate reader. Protein quantification was converted to the amount for BSA.
총당은 phenol-sulfuric acid법에 따라 측정하였으며, 시료용액 0.5 mL에 동량의 5 % phenol 용액을 첨가하여 교반한 후 진한 황산(98%, v/v) 2.5 mL를 가하여 상온에서 20분간 반응시켜 microplate reader를 이용하여 470 nm에서 흡광도를 측정하였다. 총당의 정량은 glucose 표준품(sigma aldrich)을 사용하여 검량선을 작성하여 이에 대한 양으로 환산하였다.Total sugar was measured according to the phenol-sulfuric acid method, and after stirring the same amount of 5% phenol solution to 0.5 mL of the sample solution, 2.5 mL of concentrated sulfuric acid (98%, v/v) was added and reacted at room temperature for 20 minutes to make a microplate. Absorbance was measured at 470 nm using a reader. For the determination of total sugar, a calibration curve was prepared using a glucose standard (sigma aldrich) and converted into the amount.
총 폴리페놀 함량은 gallic acid(sigma aldrich)를 이용하여 Folin Denis법에 따라 분석하였다.Total polyphenol content was analyzed according to the Folin Denis method using gallic acid (sigma aldrich).
구성당의 경우, 시료의 당사슬을 단당으로 가수분해 한 후 HPAEC-PAD(high-performance anion-exchange chromatography-pulsed amperometric detector)를 사용하였으며, 데이터는 Chromelon 6.80 소프트웨어 (Dionex)를 이용하여 분석하였다. 표준용액으로 단당류(fucose, rhamnose, arabinose, galactose, glucose, xylose)를 사용하였다. In the case of constituent sugar, the oligosaccharides of the sample were hydrolyzed to monosaccharides, and then HPAEC-PAD (high-performance anion-exchange chromatography-pulsed amperometric detector) was used, and the data were analyzed using Chromelon 6.80 software (Dionex). Monosaccharides (fucose, rhamnose, arabinose, galactose, glucose, xylose) were used as standard solutions.
그 결과, 고춧잎으로부터 열수 추출물 및 고분자 분획물의 주요성분 함량 등의 이화확적 특성을 분석한 결과 하기 표 1과 같았다.As a result, as a result of analyzing the physicochemical properties such as the content of main components of the hot water extract and the polymer fraction from red pepper leaves, it is shown in Table 1 below.
* 상기 chemical component의 함량비(%)는 건조 샘플 내의 비율을 나타낸 것이다.* The content ratio (%) of the chemical component represents the ratio in the dry sample.
표 1에 나타난 바와 같이, 실시예 1로부터 제조된 고춧잎 열수 추출물은 수율이 12.66%로 나타났으며, 단백질 함량은 4.5 중량%, 중성당 함량은 70.7 중량%로 당함량이 높은 것으로 확인되었다. 또한, 실시예 1로부터 제조된 고춧잎 열수 추출물의 구성당을 분석한 결과, 주요 구성당은 glucose(54.8 Mole %)였고, galacturonic acid, rhamnose, galactose가 각각 11.1, 9.3, 8.5 Mole %로 함유되어 있었으며, arabionose, mannose, xylose가 각각 2.5, 0.8, 0.6 Mole %로 미량 존재하고 있음을 확인하였다.As shown in Table 1, the hot-water extract of red pepper leaves prepared from Example 1 was found to have a yield of 12.66%, a protein content of 4.5% by weight, and a neutral sugar content of 70.7% by weight, indicating a high sugar content. In addition, as a result of analyzing the constituent sugars of the hot water extract of red pepper leaves prepared in Example 1, the main constituent sugar was glucose (54.8 Mole %), and galacturonic acid, rhamnose, and galactose were contained in 11.1, 9.3, and 8.5 Mole%, respectively. , arabionose, mannose, and xylose were found to be present in trace amounts of 2.5, 0.8 and 0.6 Mole%, respectively.
이에 반해, 실시예 2로부터 제조된 고춧잎 고분자 분획물의 수율은 2.68%로 낮게 나타났으나, 단백질 함량이 4.3 중량%, 중성당 함량이 52.4 중량%, 우론산이 36.7 중량%인 것으로 확인되었다. 또한 실시예 2로부터 제조된 고춧잎 고분자 분획물에서 구성당 함량은 galacturonic acid, glucose가 각각 36.0, 34.6 Mole %로 검출되었고, galactose, arabinose, rhamnose, glucuronic acid, mannose, xylose, fucose가 각각 7.1, 4.9, 3.6, 1.5, 0.8, 0.6, 0.2 Mole %로 미량 존재하고 있음을 확인하였다. 실시예 2의 고춧잎 고분자 분획물(HFPL)은 당함량이 실시예 1의 고춧잎 열수 추출물에 비해 전체적으로 감소하였으나, Arabinose, Fucose, Glucuronic acid의 함량은 소폭 증가하는 것을 확인하였다. 즉 두 추출물 내에 존재하는 구체적인 구성성분 상에 분명한 차이가 있음을 알 수 있다.On the other hand, the yield of the red pepper leaf polymer fraction prepared in Example 2 was found to be as low as 2.68%, but it was confirmed that the protein content was 4.3% by weight, the neutral sugar content was 52.4% by weight, and the uronic acid was 36.7% by weight. In addition, in the red pepper leaf polymer fraction prepared from Example 2, the constituent sugar content of galacturonic acid and glucose was detected as 36.0 and 34.6 Mole%, respectively, and galactose, arabinose, rhamnose, glucuronic acid, mannose, xylose, and fucose were 7.1, 4.9, respectively. It was confirmed that there were traces of 3.6, 1.5, 0.8, 0.6, and 0.2 Mole %. It was confirmed that the sugar content of the red pepper leaf polymer fraction (HFPL) of Example 2 was reduced overall compared to the hot water extract of red pepper leaf of Example 1, but the contents of Arabinose, Fucose, and Glucuronic acid slightly increased. That is, it can be seen that there is a clear difference between the specific components present in the two extracts.
시험예 2. 전지방 세포 분화 억제 및 지방 축적 억제 효능 분석Test Example 2. Analyzing the efficacy of inhibiting differentiation of all cells and inhibiting fat accumulation
실시예 1의 고춧잎 열수 추출물과 실시예 2의 고춧잎 고분자 분획물로부터 비만 억제 효과를 확인하고자 하였다.It was attempted to confirm the obesity inhibitory effect from the hot water extract of red pepper leaf of Example 1 and the polymer fraction of red pepper leaf of Example 2.
1) 세포 배양1) cell culture
실험을 위해 3T3-L1 전지방세포를 American Type Culture Collection(ATCC)로부터 분양받았으며, 10% 우태아혈청(Fetal bovine serum, FBS), 1% 페니실린 및 스트렙토마이신(strptomycin)(Gibco BRL, Grand Island, NY, USA)가 함유된 DMEM(Dulbecco's Modified EaDCRT Media(Gibco BRL))을 사용하여 37 ℃, 5% CO2 조건 하에서 배양하였다. 세포 수의 증식에 따른 과밀도 현상을 해소하기 위해 성장배지의 교환을 매 48시간마다 실시하여 적정 수의 세포를 유지하였다.For the experiment, 3T3-L1 whole fat cells were distributed from the American Type Culture Collection (ATCC), and 10% fetal bovine serum (FBS), 1% penicillin and strptomycin (Gibco BRL, Grand Island, NY, USA) containing DMEM (Dulbecco's Modified EaDCRT Media (Gibco BRL)) was cultured under conditions of 37°C and 5% CO 2 . In order to solve the over-density phenomenon caused by the proliferation of the number of cells, the growth medium was exchanged every 48 hours to maintain an appropriate number of cells.
(2) 분화유도(2) eruption induction
3T3-L1 세포를 0.8×105 cells/well의 밀도로 6웰 플레이트에 분주하였으며, 48시간 주기로 0.05% Trypsin-EDTA를 사용하여 계대배양 하였다. 지방세포로 분화를 유도하기 위해 MDI(0.5 mM 3-이소부틸-1-메틸잔틴(3-isobutyl-1-methylxanthin, IBMX), 1 μM 덱타메타손(dexamethasone), 10 μg/mL 인슐린(insulin)) 및 10 부피% 우태아혈청(Fetal bovine serum, FBS)이 첨가된 DMEM 분화배지에 48시간 배양하였다. 이후 10 μg/mL 인슐린만을 포함하는 배지(DMEM)로 2일마다 고체해주면서 분화가 완료되는 시점까지 계속 배양하였다. adipogenesis의 진행과정에서 고춧잎 열수 추출물과 고춧잎 고분자 분획물의 영향을 확인하기 위해, 배지를 교환할때마다 실시예 1의 고춧잎 열수 추출물 50 μg/ml(WEPL-50)과 100 μg/ml(WEPL-100), 실시예 2의 고춧잎 고분자 분획물 50 μg/ml(HFPL-50)과 100 μg/ml(HFPL-100) 및 비교예 1의 가르니시아 캄보지아 추출물 50 μg/ml(GC-50)과 100 μg/ml(GC-100)을 함께 처리하였다.3T3-L1 cells were dispensed into a 6-well plate at a density of 0.8×10 5 cells/well, and subcultured using 0.05% Trypsin-EDTA every 48 hours. To induce differentiation into adipocytes, MDI (0.5 mM 3-isobutyl-1-methylxanthin, IBMX), 1 μM dexamethasone, 10 μg/mL insulin ) And 10 vol% fetal bovine serum (FBS) were incubated for 48 hours in DMEM differentiation medium. Thereafter, the culture was continued until the differentiation was completed while solidifying every 2 days with a medium (DMEM) containing only 10 μg/mL insulin. In order to confirm the effect of the hot water extract of red pepper leaf and the polymer fraction of red pepper leaf in the process of adipogenesis, the hot water extract of red pepper leaf of Example 1 50 μg/ml (WEPL-50) and 100 μg/ml (WEPL-100) of Example 1 whenever the medium was changed. , Red pepper leaf polymer fraction of Example 2 50 μg/ml (HFPL-50) and 100 μg/ml (HFPL-100) and Garnisia cambogia extract of Comparative Example 1 50 μg/ml (GC-50) and 100 μg/ml (GC-100) was treated together.
배지를 교환시, 추출물이 아닌 지질 축적 유도 인자인 MDI(0.5 mM 3-이소부틸-1-메틸잔틴(IBMX), 1 μM 덱타메타손, 10 μg/mL 인슐린)을 함께 처리한 것을 대조군(C)으로 하였고, 아무것도 처리하지 않고 10 μg/mL 인슐린만을 포함하는 배지(DMEM)만 처리한 것을 정상군(NC)으로 하였다.When the medium was exchanged, the control (C) treated with MDI (0.5 mM 3-isobutyl-1-methylxanthine (IBMX), 1 μM dektamethasone, 10 μg/mL insulin), which is not an extract, but a lipid accumulation inducing factor. ), and treated with only a medium (DMEM) containing only 10 μg/mL insulin without any treatment, was used as a normal group (NC).
(3) Oil Red O 염색과 정량(3) Oil Red O staining and quantification
지방세포 분화가 완료된 8일째, 각각의 세포를 회수하고, 이로부터 adipogenesis 억제활성을 다음과 같이 평가하였다. 각 지방세포로 분화된 3T3-L1 세포의 지방축적량을 Oil Red O 염색법을 통해 정량 분석하기 위하여, PBS로 세척하고, 3.7% 포르말린(formalin)으로 10분간 고정하고 60% 이소프로판올(isopropanol)로 수세한 후, 각 웰을 완전히 건조하였다. oil red O 염색약을 실온에서 20분간 처리한 뒤 증류수로 4회 세척한 다음, 각 군에서 분화된 3T3-L1 지방세포의 지방구(lipid droplet)의 수와 크기를 현미경(Eclipse ti, Nikon)을 통해 관찰하였다. 정량적 분석을 위해 100% 이소프로판올을 이용하여 지방을 추출한 후 96 웰 플레이트에 200 ㎕씩 옮겨서 ELISA reader로 500 nm에서 흡광도를 측정하였고 대조군의 흡광도 값에 대한 백분율로 나타내었다.On the 8th day when adipocyte differentiation was completed, each cell was recovered, and the adipogenesis inhibitory activity was evaluated therefrom as follows. To quantitatively analyze the fat accumulation amount of 3T3-L1 cells differentiated into each adipocyte by Oil Red O staining, wash with PBS, fix with 3.7% formalin for 10 minutes, and wash with 60% isopropanol. Thereafter, each well was completely dried. Oil red O dye was treated at room temperature for 20 minutes, washed 4 times with distilled water, and then the number and size of lipid droplets of 3T3-L1 adipocytes differentiated from each group were measured under a microscope (Eclipse ti, Nikon). Observed through. For quantitative analysis, fat was extracted using 100% isopropanol, transferred to a 96-well plate 200 μl each, and the absorbance was measured at 500 nm with an ELISA reader, and expressed as a percentage of the absorbance value of the control group.
(4) 3T3-L1 지방전구세포의 지방구 생성에 미치는 고춧잎 추출물의 영향(4) Effect of red pepper leaf extract on the formation of adipocytes in 3T3-L1 adipocytes
3T3-L1 지방전구세포가 지방세포로의 분화과정에 나타나는 lipid droplet 생성이 고춧잎 열수 추출물 또는 고춧잎 고분자 분획물 처리에 의해 억제되는지의 여부를 조사하였다.It was investigated whether the formation of lipid droplets appearing in the process of differentiation of 3T3-L1 adipocytes into adipocytes was inhibited by treatment with hot water extract of red pepper leaf or polymer fraction of red pepper leaf.
도 1은 실시예 1로부터 제조된 고춧잎 열수 추출물 및 실시예 2로부터 제조된 고춧잎 고분자 분획물 처리에 의한 3T3-L1 세포내 지질함량 변화를 확인하기 위한 Oil red O 염색결과이다. 도 2는 실시예 1로부터 제조된 고춧잎 열수 추출물 및 실시예 2로부터 제조된 고춧잎 고분자 분획물의 지방세포분화 억제효능을 실험한 결과이다.1 is an Oil red O staining result for confirming the change in lipid content in 3T3-L1 cells by treatment with hot water extract of red pepper leaf prepared from Example 1 and polymer fraction of red pepper leaf prepared from Example 2. FIG. Figure 2 is a result of testing the effect of inhibiting adipocyte differentiation of the hot water extract of red pepper leaf prepared in Example 1 and the polymer fraction of red pepper leaf prepared in Example 2. FIG.
도 1 및 2에 나타난 바와 같이, 지질축적을 유도한 대조군(C)보다 WEPL군 또는 HFPL군에서 모두 지방합성이 억제되었음을 알 수 있다. 특히 WEPL-100군에서 지방세포 분화와 지방생성을 억제시키는 효능이 가장 뛰어났다.As shown in Figs. 1 and 2, it can be seen that fat synthesis was suppressed in both the WEPL group or the HFPL group than the control group (C) in which lipid accumulation was induced. In particular, in the WEPL-100 group, the effect of inhibiting adipocyte differentiation and adipogenesis was the most excellent.
도 2에 따르면, 지질축적을 유도한 대조군(C)에 비해 가르시니아 캄보지아 추출물(비교예 1)을 처리한 GC-50군은 약 10.3%의 지방 축적 억제력을 나타내었으며, WEPL-50군과 WEPL-100군은 각각 1.9%, 7.6%의 지방 축적 억제력을 나타내었다. 또한, HFPL-50군과 HFPL-100군은 각각 3.0%, 13.7%의 지방 축적 억제력을 나타내었다. 종합하면, 본 발명에 따른 고춧잎 추출물뿐만 아니라 고춧잎 고분자 분획물은 3T3-L1 지방전구세포에서 지방세포로의 분화 및 지방생성을 억제하는 효과를 나타내며, 이는 종래 가르시니아 캄보지아 추출물과 동등한 수준임을 확인하였다. 가르시니아 캄보지아 추출물의 경우 인체 내에서 부작용을 유발하는 것으로 알려져 있어 실적용에 한계가 있지만 본 발명의 고춧잎 추출물 또는 고춧잎 고분자 분획물은 생체 내 독성이 거의 나타나지 않으므로 활용에 한계가 없다는 장점이 있다.According to FIG. 2, the GC-50 group treated with the garcinia cambogia extract (Comparative Example 1) compared to the control group (C) inducing lipid accumulation showed about 10.3% fat accumulation inhibitory ability, and the WEPL-50 group and WEPL-
시험예 3. 실시예 1의 고춧잎 열수 추출물의 비만, 대사성질환 관련 인자 분석Test Example 3. Analysis of factors related to obesity and metabolic diseases of hot water extract of red pepper leaves of Example 1
(1) 실험동물 및 식이(1) Experimental animals and diet
무균 환경에서 사육된 6주령의 수컷 C57BL/6J계 마우스 45마리를 (주)중앙실험동물에서 구입하였으며, 마우스 사육조건은 온도 22 ± 2 ℃, 습도는 40-60%로 유지하였고, 명암 주기(Light and dark cycle)는 12시간 간격으로 조절하였다.45 6-week-old male C57BL/6J-based mice bred in a sterile environment were purchased from Central Experimental Animal Co., Ltd., and the mouse breeding conditions were kept at a temperature of 22 ± 2 ℃ and a humidity of 40-60%. Light and dark cycle) was adjusted at 12 hour intervals.
상기 마우스를 9마리씩 5군으로 나누고, 실험식이를 공급하여 8주간 사육하였다. 실험식이는 고지방 사료(high fat diet)로, Lard를 첨가하여 열량을 60 cal%를 증가시킨 Modified AIN 76A purified rodent diet(60 cal% fat)를 자유급식하였으며, 정상군(NC), 고지방 식이 대조군(HF), 비교예 1의 가르시니아 캄보지아 추출물을 50 mg/kg 투여한 양성 대조군(GC), 실시예 1의 고춧잎 추출물 50 mg/kg 투여군(WEPL50) 및 실시예 1의 고춧잎 추출물 100 mg/kg 투여군(WEPL100)으로 실험군을 나누어 실험하였다. 물과 실험식이는 자유롭게 섭취하도록 하였으며, 실험기간 동안의 체중 증가량은 실험식이를 시작한 날을 기준으로 8주간 1주일 간격으로 오전 10시에 체중을 측정하였다. 상기 비교예 1의 가르시니아 캄보지아 추출물과 실시예 1의 고춧잎 추출물은 각각 멸균식염수에 용해하여 경구투여하였다.The mice were divided into 5 groups of 9 mice each, and an experimental diet was supplied and reared for 8 weeks. The experimental diet was a high fat diet, and a modified AIN 76A purified rodent diet (60 cal% fat), which increased calories by 60 cal% by adding Lard, was fed freely, and the normal group (NC), the high fat diet control group (HF), a positive control group (GC) in which 50 mg/kg of garcinia cambogia extract of Comparative Example 1 was administered, a 50 mg/kg administration group of red pepper leaf extract of Example 1 (WEPL50), and a 100 mg/kg administration group of red pepper leaf extract of Example 1 The experimental group was divided into (WEPL100) and the experiment was conducted. Water and the experimental diet were freely ingested, and the weight gain during the experiment was measured at 10 am at 1 week intervals for 8 weeks from the start of the experimental diet. The garcinia cambogia extract of Comparative Example 1 and the red pepper leaf extract of Example 1 were each dissolved in sterile saline and administered orally.
(2) 혈액과 장기의 채취(2) Collection of blood and organs
실험이 종료되고, 실험동물을 12시간 절식을 시킨 후, 아이프란액을 이용하여 마취하고 복부와 흉강을 절개하여 간문맥에서 채취한 혈액을 응고시킨 후 혈청을 분리하여 혈청지질 및 비만관련 호르몬의 농도를 분석하는데 이용하였다. 각각의 실험동물로부터 백색 부고환 지방조직 및 기타 장기를 적출하여 생리 식염수를 이용해 혈액 및 이물질을 제거하고 무게를 측정한 후, -80 ℃에서 분석시까지 보관하였다.After the experiment was completed, the experimental animals were fasted for 12 hours, anesthetized with iFran solution, the abdomen and chest cavity were incised to coagulate the blood collected from the portal vein, and then the serum was separated and the concentration of serum lipids and obesity-related hormones Was used to analyze. White epididymal adipose tissue and other organs were removed from each experimental animal, blood and foreign substances were removed using physiological saline, weighed, and stored at -80°C until analysis.
(3) 체중 변화 및 체지방량 분석(3) weight change and body fat mass analysis
도 3은 정상군(NC), 고지방 식이 대조군(HF), 비교예 1의 가르시니아 캄보지아 추출물을 50 mg/kg 투여한 양성 대조군(GC), 실시예 1의 고춧잎 추출물 50 mg/kg 투여군(WEPL50) 및 실시예 1의 고춧잎 추출물 100 mg/kg 투여군(WEPL100)에서의 시간별 체중변화를 나타낸 그래프이고, 도 4는 정상군(NC), 고지방 식이 대조군(HF), 비교예 1의 가르시니아 캄보지아 추출물을 50 mg/kg 투여한 양성 대조군(GC), 실시예 1의 고춧잎 추출물 50 mg/kg 투여군(WEPL50) 및 실시예 1의 고춧잎 추출물 100 mg/kg 투여군(WEPL100)에서 백색 부고환 지방 조직을 적출한 후, 무게를 측정하여 나타낸 그래프이다.3 is a normal group (NC), a high-fat diet control (HF), a positive control (GC) in which 50 mg/kg of the garcinia cambogia extract of Comparative Example 1 was administered, and a 50 mg/kg administration group of red pepper leaf extract of Example 1 (WEPL50) And it is a graph showing the weight change over time in the 100 mg / kg administration group (WEPL100) of red pepper leaf extract of Example 1, Figure 4 is a normal group (NC), high fat diet control (HF), the garcinia cambogia extract of Comparative Example 1 50 After extracting white epididymal adipose tissue from the positive control group administered with mg/kg (GC), the red pepper leaf extract 50 mg/kg administration group (WEPL50) of Example 1, and the red
도 3에 나타난 바와 같이, 정상군(NC)에 비하여, 고지방 식이 대조군(HF)는 체중(11.9 g 증가)이 유의적으로 높은 증가를 나타내었다. 이에 반해 비교예 1의 가르시니이아 캄보지아 추출물, 실시예 1의 고춧잎 추출물을 경구투여한 군은 고지방 식이 대조군(HF)이 비하여 체중이 유의적으로 감소하는 경향을 보였다. 구체적으로 고지방 식이를 하면서 가르니시아 캄보지아 추출물(비교예 1) 50 mg/kg을 경구투여한 군(GC)은 고지방 식이 대조군(HF)에 비해 26.9% 체중이 감소하였고, 고지방 식이를 하면서 고춧잎 추출물 50 mg/kg 투여군(WEPL50)과 100 mg/kg 투여군(WEPL100)은 고지방 식이 대조군(HF)에 비해 각각 25.1% 및 28.5% 체중이 감소하였다. 특히 실시예 1의 고춧잎 추출물이 100 mg/kg 경구투여된 WEPL-100군은 양성대조군(GC군)에 비하여 체중이 유의적으로 감소하였다(p<0.05).As shown in FIG. 3, compared to the normal group (NC), the high fat diet control group (HF) showed a significantly higher increase in body weight (11.9 g increase). On the other hand, the group to which the garcinia cambogia extract of Comparative Example 1 and the red pepper leaf extract of Example 1 were administered orally showed a tendency to significantly decrease body weight compared to the high-fat diet control group (HF). Specifically, the group (GC) to which 50 mg/kg of Garnisia cambogia extract (Comparative Example 1) was orally administered while on a high fat diet (GC) lost 26.9% body weight compared to the high fat diet control group (HF), and red
도 4에 나타난 바와 같이 각 실험군에서 적출한 백색 부고환 지방량은 정상군(NV)에 비해 고지방 식이 대조군(HF)에서 유의하게 증가하였다. 실시예 1의 고춧잎 추출물을 투여한 WEPL-50군과 WEPL-100군은 고지방 식이 대조군(HF)에 비하여 백색 부고환 지방조직의 무게가 약 2.7%, 16.1% 감소하였음을 확인하였다. 따라서 본 발명의 고춧잎 추출물은 지방 조직의 무게를 감소시키는 효과가 있고, 체중 감량뿐만 아니라 체지방의 증가를 억제하는 것을 알 수 있다.As shown in FIG. 4, the amount of white epididymal fat extracted from each experimental group was significantly increased in the high-fat diet control group (HF) compared to the normal group (NV). It was confirmed that the weight of the white epididymal adipose tissue was reduced by about 2.7% and 16.1% in the WEPL-50 group and the WEPL-100 group to which the pepper leaf extract of Example 1 was administered compared to the high fat diet control group (HF). Therefore, it can be seen that the red pepper leaf extract of the present invention has an effect of reducing the weight of adipose tissue, and suppresses an increase in body fat as well as weight loss.
(4) 혈장 지질함량 분석(4) Plasma lipid content analysis
혈청의 엔도톡신, 중성지방, 총 콜레스테롤의 농도는 (주) 신양화학의 혈액분석용 키트를 이용하여 효소법으로 분석하였다. 중성지방은 Tiglyzyme-V, 총 콜레스테롤은 Cholestezyme-V로 분석하였다. Pierce™ LAL Chromogenic Endotoxin Quantitation Kit(Thermo scientific)를 이용하여 마우스 혈청 내 Endotoxin양을 확인하였다.The concentrations of endotoxin, triglyceride, and total cholesterol in serum were analyzed by enzyme method using a blood analysis kit of Shinyang Chemical Co., Ltd. Triglycerides were analyzed by Tiglyzyme-V and total cholesterol by Cholestezyme-V. Pierce™ LAL Chromogenic Endotoxin Quantitation Kit (Thermo scientific) was used to determine the amount of Endotoxin in mouse serum.
도 5는 정상군(NC), 고지방 식이 대조군(HF), 비교예 1의 가르시니아 캄보지아 추출물을 50 mg/kg 투여한 양성 대조군(GC), 실시예 1의 고춧잎 추출물 50 mg/kg 투여군(WEPL50) 및 실시예 1의 고춧잎 추출물 100 mg/kg 투여군(WEPL100)으로부터 적출한 혈청 내 엔도톡신 농도를 측정하여 나타낸 그래프이고, 도 6은 정상군(NC), 고지방 식이 대조군(HF), 비교예 1의 가르시니아 캄보지아 추출물을 50 mg/kg 투여한 양성 대조군(GC), 실시예 1의 고춧잎 추출물 50 mg/kg 투여군(WEPL50) 및 실시예 1의 고춧잎 추출물 100 mg/kg 투여군(WEPL100)로부터 적출한 혈청 내 중성지방 농도를 측정하여 나타낸 그래프이며, 도 7은 정상군(NC), 고지방 식이 대조군(HF), 비교예 1의 가르시니아 캄보지아 추출물을 50 mg/kg 투여한 양성 대조군(GC), 실시예 1의 고춧잎 추출물 50 mg/kg 투여군(WEPL50) 및 실시예 1의 고춧잎 추출물 100 mg/kg 투여군(WEPL100)로부터 적출한 혈청 내 총 콜레스테롤 농도를 측정하여 나타낸 그래프이다.5 is a normal group (NC), a high-fat diet control group (HF), a positive control group (GC) in which 50 mg/kg of garcinia cambogia extract of Comparative Example 1 was administered, and a 50 mg/kg administration group of red pepper leaf extract of Example 1 (WEPL50) And it is a graph showing by measuring the concentration of endotoxin in the serum extracted from the 100 mg / kg administration group (WEPL100) of red pepper leaf extract of Example 1, Figure 6 is a normal group (NC), a high-fat diet control group (HF), Garcinia of Comparative Example 1 Neutrality in serum extracted from the positive control group (GC) administered with 50 mg/kg of Cambogia extract, 50 mg/kg administration group of red pepper leaf extract of Example 1 (WEPL50) and 100 mg/kg administration group of red pepper leaf extract of Example 1 (WEPL100) It is a graph showing the measurement of fat concentration, and FIG. 7 is a normal group (NC), a high-fat diet control (HF), a positive control (GC) administered with 50 mg/kg of garcinia cambogia extract of Comparative Example 1, and red pepper leaves of Example 1 It is a graph showing the total cholesterol concentration in the serum extracted from the extract 50 mg/kg administration group (WEPL50) and the pepper leaf extract 100 mg/kg administration group (WEPL100) of Example 1.
도 5에 나타난 바와 같이, 엔도톡신은 정상군(NC)에 비해 고지방 식이 대조군(HF)에서 106.3% 증가하였으나, WEPL-50군 및 WEPL-100군은 고지방 식이 대조군(HF)에 비해 각각 14.6% 및 32.9% 감소하였으므로, 실시예 1의 고춧잎 추출물은 혈청 내 엔도톡신의 농도를 감소시켜 비만을 억제함과 동시에 비만으로 인해 유도되는 염증도 예방하는 효과를 가짐을 확인하였다.As shown in Figure 5, endotoxin increased 106.3% in the high fat diet control group (HF) compared to the normal group (NC), but the WEPL-50 group and the WEPL-100 group were 14.6% and respectively compared to the high fat diet control group (HF). Since the decrease was 32.9%, it was confirmed that the red pepper leaf extract of Example 1 reduced the concentration of endotoxin in the serum to suppress obesity and at the same time prevent inflammation induced by obesity.
도 6 및 7에 따르면, 중성지방 및 총 콜레스테롤은 정상군(NC)에 비해 고지방 식이 대조군(HF)에서 유의하게 증가하였으나, WEPL-50군 및 WEPL-100군은 고지방 식이 대조군(HF)에 비해 유의하게 감소하였다. 본 발명에 따른 실시예 1의 고춧잎 추출물은 고지방 식이와 병용투여됨에도 불과하고, 정상군(NC)과 유사한 중성지방과 총 콜레스테롤을 나타내었는 바, 비만 억제 효과가 현저히 우수함을 알 수 있다.6 and 7, triglyceride and total cholesterol were significantly increased in the high fat diet control group (HF) compared to the normal group (NC), but the WEPL-50 group and the WEPL-100 group were compared to the high fat diet control group (HF). Significantly decreased. The red pepper leaf extract of Example 1 according to the present invention was only co-administered with a high fat diet, and showed triglyceride and total cholesterol similar to those of the normal group (NC), and it can be seen that the obesity inhibitory effect is remarkably excellent.
(5) 혈장 중 지방분화 관련 호르몬(렙틴, 인슐린)(5) Plasma fat differentiation related hormones (leptin, insulin)
혈청내 지방분화 관련 호르몬인 렙틴(mouse leptin ELISA kit, R&D systems, Minneapolis, USA)과 인슐린(mouse insulin ELISA kit, ALPCO, New Hampshire, USA)의 농도를 ELISA 분석법을 이용하여 분석하였다.The concentrations of leptin (mouse leptin ELISA kit, R&D systems, Minneapolis, USA) and insulin (mouse insulin ELISA kit, ALPCO, New Hampshire, USA) were analyzed using ELISA assay.
도 8은 정상군(NC), 고지방 식이 대조군(HF), 비교예 1의 가르시니아 캄보지아 추출물을 50 mg/kg 투여한 양성 대조군(GC), 실시예 1의 고춧잎 추출물 50 mg/kg 투여군(WEPL50) 및 실시예 1의 고춧잎 추출물 100 mg/kg 투여군(WEPL100)으로부터 적출한 혈청 내 렙틴 농도를 측정하여 나타낸 그래프이고, 도 9는 정상군(NC), 고지방 식이 대조군(HF), 비교예 1의 가르시니아 캄보지아 추출물을 50 mg/kg 투여한 양성 대조군(GC), 실시예 1의 고춧잎 추출물 50 mg/kg 투여군(WEPL50) 및 실시예 1의 고춧잎 추출물 100 mg/kg 투여군(WEPL100)으로부터 적출한 혈청 내 인슐린 농도를 측정하여 나타낸 그래프이다.Figure 8 is a normal group (NC), a high-fat diet control (HF), a positive control (GC) administered with 50 mg/kg of the garcinia cambogia extract of Comparative Example 1, and a 50 mg/kg administration group of red pepper leaf extract of Example 1 (WEPL50) And a graph showing the concentration of leptin in serum extracted from the 100 mg/kg administration group (WEPL100) of the red pepper leaf extract of Example 1, and FIG. 9 is a normal group (NC), a high-fat diet control group (HF), and a garcinia of Comparative Example 1. Insulin in serum extracted from positive control (GC) administered with 50 mg/kg of Cambogia extract, 50 mg/kg administration group of red pepper leaf extract of Example 1 (WEPL50) and 100 mg/kg administration group of red pepper leaf extract of Example 1 (WEPL100) This is a graph showing the concentration measured.
도 8 및 9에 나타난 바와 같이, 렙틴은 지방조직에서 생성되어 분비되는 호르몬으로 혈중 농도가 체지방량에 비례하여 식욕을 억제하고 에너지 소비를 증가시켜 에너지 대사 및 체중 조절에 관여하는 것으로 알려져 있다. 렙틴 농도가 고지방 식이 대조군(HF) 대비 GC군, WEPL-50군, WEPL-100군에서 각각 31.8%, 18.2%, 39.1% 감소하였다. 또한, 혈청 내 인슐린 농도를 측정한 결과, 고지방 식이 대조군(HF) 대비 GC군, WEPL-50군 및 WEPL-100군은 각각 32.3%, 18.1% 및 38.9% 감소하였다. 따라서 실시에 1의 고춧잎 추출물은 혈청 내 렙틴 및 인슐린 농도를 유의적으로 감소시키는 결과를 나타내었으며, 이는 체지방량의 감소와 연관되어 있다.As shown in FIGS. 8 and 9, leptin is a hormone produced and secreted by adipose tissue, and it is known to be involved in energy metabolism and weight control by suppressing appetite and increasing energy consumption in proportion to the amount of body fat in blood. The leptin concentration decreased by 31.8%, 18.2%, and 39.1% in the GC group, WEPL-50 group, and WEPL-100 group, respectively, compared to the high fat diet control group (HF). In addition, as a result of measuring the serum insulin concentration, the GC group, WEPL-50 group, and WEPL-100 group decreased by 32.3%, 18.1% and 38.9%, respectively, compared to the high fat diet control group (HF). Therefore, the red pepper leaf extract of Example 1 showed a result of significantly reducing the concentration of leptin and insulin in the serum, which is associated with a decrease in body fat mass.
실시예 1의 고춧잎 추출물은 앞선 결과들을 종합하였을 때, 50 mg/kg 이상 사용되면 비만 개선, 예방 또는 치료효과를 나타내는 것으로 확인되나, 100 mg/kg 이상 일 때 가장 우수한 효과를 나타내므로 보다 바람직하고, 10 g/kg 이상의 농도로 사용되면 효과의 증가가 없으므로, 100 내지 10,000 mg/kg의 농도로 사용되는 것이 가장 바람직하다.When the above results are summarized, the red pepper leaf extract of Example 1 is confirmed to exhibit an improvement, prevention or treatment effect on obesity when 50 mg/kg or more is used, but it is more preferable because it shows the best effect when it is 100 mg/kg or more. , Since there is no increase in the effect when used in a concentration of 10 g/kg or more, it is most preferably used in a concentration of 100 to 10,000 mg/kg.
하기에 본 발명의 분말을 함유하는 조성물의 제제예를 설명하나, 본 발명은 이를 한정하고자 함이 아닌 단지 구체적으로 설명하고자 함이다.Hereinafter, examples of the formulation of the composition containing the powder of the present invention are described, but the present invention is not intended to limit it, but is intended to be described in detail.
제제예 1. 산제의 제조Formulation Example 1. Preparation of powder
실시예 1에서 얻은 고춧잎 열수 추출물 또는 실시예 2에서 얻은 고춧잎 고분자 분획물 500 ㎎Hot water extract of red pepper leaves obtained in Example 1 or polymer fraction of red pepper leaves obtained in Example 2 500 mg
유당 100 ㎎100 mg lactose
탈크 10 ㎎Talc 10 mg
상기의 성분들을 혼합하고 기밀포에 충진하여 산제를 제조한다.The above ingredients are mixed and filled in an airtight cloth to prepare a powder.
제제예 2. 정제의 제조Formulation Example 2. Preparation of tablet
실시예 1에서 얻은 고춧잎 열수 추출물 또는 실시예 2에서 얻은 고춧잎 고분자 분획물 300 ㎎Hot water extract of red pepper leaves obtained in Example 1 or polymer fraction of red pepper leaves obtained in Example 2 300 mg
옥수수전분
100 ㎎
유당
100 ㎎
스테아린산 마그네슘 2 ㎎2 mg of magnesium stearate
상기의 성분들을 혼합한 후 통상의 정제의 제조방법에 따라서 타정하여 정제를 제조한다.After mixing the above ingredients, tablets are prepared by tableting according to a conventional tablet preparation method.
제제예 3. 캅셀제의 제조Formulation Example 3. Preparation of Capsule
실시예 1에서 얻은 고춧잎 열수 추출물 또는 실시예 2에서 얻은 고춧잎 고분자 분획물 200 ㎎Hot water extract of red pepper leaves obtained in Example 1 or polymer fraction of red pepper leaves obtained in Example 2 200 mg
결정성 셀룰로오스 3 ㎎
락토오스 14.8 ㎎Lactose 14.8 mg
마그네슘 스테아레이트 0.2 ㎎Magnesium stearate 0.2 mg
통상의 캡슐제 제조방법에 따라 상기의 성분을 혼합하고 젤라틴 캡슐에 충전하여 캡슐제를 제조한다.According to a conventional capsule preparation method, the above ingredients are mixed and filled into gelatin capsules to prepare a capsule.
제제예 4. 주사제의 제조Formulation Example 4. Preparation of injection
실시예 1에서 얻은 고춧잎 열수 추출물 또는 실시예 2에서 얻은 고춧잎 고분자 분획물 600 ㎎Hot water extract of red pepper leaves obtained in Example 1 or polymer fraction of red pepper leaves obtained in Example 2 600 mg
만니톨 180 ㎎Mannitol 180 mg
주사용 멸균 증류수 2974 ㎎2974 mg of sterile distilled water for injection
Na2HPO4,12H2O 26 ㎎Na 2 HPO 4, 12H 2 O 26 mg
통상의 주사제의 제조방법에 따라 1 앰플 당 상기의 성분 함량으로 제조한다.It is prepared with the above ingredients per ampoule according to a conventional injection preparation method.
제제예 5. 액제의 제조Formulation Example 5. Preparation of liquid formulation
실시예 1에서 얻은 고춧잎 열수 추출물 또는 실시예 2에서 얻은 고춧잎 고분자 분획물 4 gHot water extract of red pepper leaves obtained in Example 1 or polymer fraction of red pepper leaves obtained in Example 2 4 g
이성화당 10 g10 g of isomerized sugar
만니톨 5 g5 g of mannitol
정제수 적량Purified water appropriate amount
통상의 액제의 제조방법에 따라 정제수에 각각의 성분을 가하여 용해시키고 레몬향을 적량 가한 다음 상기의 성분을 혼합한 다음 정제수를 가하여 전체를 정제수를 가하여 전체 100g으로 조절한 후 갈색병에 충진하여 멸균시켜 액제를 제조한다.According to the usual preparation method of liquid preparation, add each ingredient to purified water to dissolve it, add lemon zest, mix the above ingredients, add purified water and add purified water to adjust the total to 100g, then fill in a brown bottle for sterilization. To prepare a solution.
제제예 6. 과립제의 제조Formulation Example 6. Preparation of granules
실시예 1에서 얻은 고춧잎 열수 추출물 또는 실시예 2에서 얻은 고춧잎 고분자 분획물 1,000 ㎎Hot water extract of red pepper leaves obtained in Example 1 or polymer fraction of red pepper leaves obtained in Example 2 1,000 mg
비타민 혼합물 적량Vitamin mixture right amount
비타민 A 아세테이트 70 ㎍Vitamin A acetate 70 ㎍
비타민 E 1.0 ㎎Vitamin E 1.0 mg
비타민 B1 0.13 ㎎Vitamin B1 0.13 mg
비타민 B2 0.15 ㎎Vitamin B2 0.15 mg
비타민 B6 0.5 ㎎Vitamin B6 0.5 mg
비타민 B12 0.2 ㎍Vitamin B12 0.2 ㎍
비타민 C 10 ㎎Vitamin C 10 mg
비오틴 10 ㎍Biotin 10 ㎍
니코틴산아미드 1.7 ㎎Nicotinic acid amide 1.7 mg
엽산 50 ㎍
판토텐산 칼슘 0.5 ㎎0.5 mg of calcium pantothenate
무기질 혼합물 적량Suitable amount of inorganic mixture
황산제1철 1.75 ㎎Ferrous sulfate 1.75 mg
산화아연 0.82 ㎎Zinc oxide 0.82 mg
탄산마그네슘 25.3 ㎎Magnesium carbonate 25.3 mg
제1인산칼륨 15 ㎎Potassium monophosphate 15 mg
제2인산칼슘 55 ㎎Dicalcium phosphate 55 mg
구연산칼륨 90 ㎎Potassium citrate 90 mg
탄산칼슘 100 ㎎100 mg of calcium carbonate
염화마그네슘 24.8 ㎎Magnesium chloride 24.8 mg
상기의 비타민 및 미네랄 혼합물의 조성비는 비교적 과립제에 적합한 성분을 바람직한 실시예로 혼합 조성하였지만, 그 배합비를 임의로 변형 실시하여도 무방하며, 통상의 과립제 제조방법에 따라 상기의 성분을 혼합한 다음, 과립을 제조하고, 통상의 방법에 따라 건강기능식품 조성물 제조에 사용할 수 있다.The composition ratio of the vitamin and mineral mixture is relatively suitable for granules, but it is possible to arbitrarily modify the mixing ratio. After mixing the above ingredients according to a conventional granule preparation method, granules And can be used to prepare a health functional food composition according to a conventional method.
제제예 7. 기능성 음료의 제조Formulation Example 7. Preparation of functional beverage
실시예 1에서 얻은 고춧잎 열수 추출물 또는 실시예 2에서 얻은 고춧잎 고분자 분획물 1,000 ㎎Hot water extract of red pepper leaves obtained in Example 1 or polymer fraction of red pepper leaves obtained in Example 2 1,000 mg
구연산 1,000 ㎎Citric acid 1,000 mg
올리고당 100 g100 g oligosaccharides
매실농축액 2 g2 g of plum concentrate
타우린 1 g1 g taurine
정제수를 가하여 전체 900 ㎖Total 900 ml by adding purified water
통상의 건강음료 제조방법에 따라 상기의 성분을 혼합한 다음, 약 1 시간 동안 85 ℃에서 교반 가열한 후, 만들어진 용액을 여과하여 멸균된 2 L 용기에 취득하여 밀봉 멸균한 뒤 냉장 보관한 다음 본 발명의 기능성 음료 조성물 제조에 사용한다. After mixing the above ingredients according to a normal health drink manufacturing method, stirring and heating the resulting solution at 85°C for about 1 hour, the resulting solution is filtered and obtained in a sterilized 2 L container, sealed and sterilized, and stored in a refrigerator. It is used to prepare the functional beverage composition of the invention.
상기 조성비는 비교적 기호음료에 적합한 성분을 바람직한 실시예로 혼합 조성하였지만, 수요계층, 수요국가, 사용용도 등 지역적, 민족적 기호도에 따라서 그 배합비를 임의로 변형 실시하여도 무방하다.The composition ratio is composed of ingredients suitable for a relatively preferred beverage in a preferred embodiment, but the mixing ratio may be arbitrarily modified according to regional and ethnic preferences, such as the demand class, the country of demand, and the purpose of use.
Claims (6)
상기 고춧잎 추출물은 물, 탄소수 1 내지 4개의 알코올 또는 이들의 혼합용매로 추출된 것을 특징으로 하는 비만 혹은 대사성질환 개선 또는 예방용 식품 조성물.The method of claim 1,
The red pepper leaf extract is a food composition for improving or preventing obesity or metabolic diseases, characterized in that the extract is extracted with water, alcohol having 1 to 4 carbon atoms, or a mixed solvent thereof.
상기 조성물은 전지방세포 분화와 지방 축적을 억제하며, 체중과 체지방의 증가를 감소시키며, 혈청 내 엔도톡신, 중성지방 및 총 콜레스테롤 농도를 낮추고, 혈청 내 지방분화 관련 호르몬의 발현을 억제하는 것을 특징으로 하는 비만 혹은 대사성질환 개선 또는 예방용 식품 조성물.The method of claim 1,
The composition is characterized in that it inhibits proliferative cell differentiation and fat accumulation, reduces the increase in body weight and body fat, lowers the concentration of endotoxin, triglyceride and total cholesterol in the serum, and inhibits the expression of hormones related to fat differentiation in the serum. A food composition for improving or preventing obesity or metabolic diseases.
상기 고춧잎 추출물은 물, 탄소수 1 내지 4개의 알코올 또는 이들의 혼합용매로 추출된 것을 특징으로 하는 비만 혹은 대사성질환 예방 또는 치료용 약학 조성물.The method of claim 4,
The red pepper leaf extract is a pharmaceutical composition for preventing or treating obesity or metabolic diseases, characterized in that the extract is extracted with water, alcohol having 1 to 4 carbon atoms, or a mixed solvent thereof.
상기 조성물은 전지방세포 분화와 지방 축적을 억제하며, 체중과 체지방의 증가를 감소시키며, 혈청 내 엔도톡신, 중성지방 및 총 콜레스테롤 농도를 낮추고, 혈청 내 지방분화 관련 호르몬의 발현을 억제하는 것을 특징으로 하는 비만 혹은 대사성질환 혹은 대사성질환 예방 또는 치료용 약학 조성물.The method of claim 4,
The composition is characterized in that it inhibits proliferative cell differentiation and fat accumulation, reduces the increase in body weight and body fat, lowers the concentration of endotoxin, triglyceride and total cholesterol in the serum, and inhibits the expression of hormones related to fat differentiation in the serum. A pharmaceutical composition for preventing or treating obesity or metabolic disease or metabolic disease.
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KR20220132349A (en) * | 2021-03-23 | 2022-09-30 | (주)고추와 육종 | Composition for preventing, ameliorating or treating metabolic disease comprising leaf extract of new pepper cultivar as effective component |
KR20230140800A (en) | 2022-03-30 | 2023-10-10 | 박병희 | A composition for preventing, treating, or improving obesity and diabetes, comprising a novel Lactococcus lactis subspace cremoris fermented chilli pepper extract |
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KR20160059152A (en) | 2014-11-18 | 2016-05-26 | 임실생약영농조합법인 | Anti-obesity composition comprising Cirsium japonicum leaf extract as effective component |
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JP4742204B2 (en) * | 2005-01-21 | 2011-08-10 | 財団法人ヒューマンサイエンス振興財団 | Adipocyte differentiation regulator |
KR100728055B1 (en) * | 2005-02-24 | 2007-06-13 | (주)바이오뉴트리젠 | food for preventing fatness and hyperlipemia |
KR101237694B1 (en) * | 2010-12-22 | 2013-02-26 | 김경술 | Anti-diabetic extract of pan-fried tea of pepper leaf |
KR101356611B1 (en) * | 2012-07-04 | 2014-02-04 | 전북대학교산학협력단 | Vinegar of fermented pepper leaf with increased AGI activity and method for preparing the same |
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KR20160059152A (en) | 2014-11-18 | 2016-05-26 | 임실생약영농조합법인 | Anti-obesity composition comprising Cirsium japonicum leaf extract as effective component |
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KR20220132349A (en) * | 2021-03-23 | 2022-09-30 | (주)고추와 육종 | Composition for preventing, ameliorating or treating metabolic disease comprising leaf extract of new pepper cultivar as effective component |
KR20230140800A (en) | 2022-03-30 | 2023-10-10 | 박병희 | A composition for preventing, treating, or improving obesity and diabetes, comprising a novel Lactococcus lactis subspace cremoris fermented chilli pepper extract |
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