KR101227737B1 - A composition comprising Ligularia stenocephala extract, fractions thereof or compounds isolated from Ligularia stenocephala extract and fractions thereof having peroxinitrite-scavenging activity - Google Patents

A composition comprising Ligularia stenocephala extract, fractions thereof or compounds isolated from Ligularia stenocephala extract and fractions thereof having peroxinitrite-scavenging activity Download PDF

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KR101227737B1
KR101227737B1 KR1020100008785A KR20100008785A KR101227737B1 KR 101227737 B1 KR101227737 B1 KR 101227737B1 KR 1020100008785 A KR1020100008785 A KR 1020100008785A KR 20100008785 A KR20100008785 A KR 20100008785A KR 101227737 B1 KR101227737 B1 KR 101227737B1
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박희준
이병일
김원배
최종원
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Abstract

본 발명은 곤달비 추출물 또는 이의 분획물, 또는 이들로부터 유래된 화합물을 유효성분으로 하는 퍼옥시니트라이트 소거 활성을 갖는 조성물에 관한 것으로 이 조성물은 비만 관련 질환의 예방 또는 치료에 효과적이므로 비만 관련 질환의 개선, 예방, 및 치료를 위한 약학적 조성물, 식품 조성물, 화장료 조성물, 및 의약외품 조성물 등으로 사용될 수 있다. The present invention relates to a composition having a peroxynitrite scavenging activity comprising a gondal extract or a fraction thereof, or a compound derived therefrom as an active ingredient, which is effective for preventing or treating obesity-related diseases and thus improving obesity-related diseases. It can be used as a pharmaceutical composition, food composition, cosmetic composition, quasi-drug composition and the like for the prevention, and treatment.

Description

곤달비 추출물, 이의 분획물, 또는 이로부터 분리한 화합물을 유효성분으로 함유하는 퍼옥시니트라이트 소거 활성을 갖는 조성물{A composition comprising Ligularia stenocephala extract, fractions thereof or compounds isolated from Ligularia stenocephala extract and fractions thereof having peroxinitrite-scavenging activity} A composition comprising Ligularia stenocephala extract, fractions according or compounds isolated from Ligularia stenocephala extract and fractions having having peroxinitrite- scavenging activity}

본 발명은 곤달비 추출물 또는 이의 분획물, 또는 이들로부터 유래된 화합물을 유효성분으로 하는 퍼옥시니트라이트 소거 활성을 갖는 조성물에 관한 것이다.
The present invention relates to a composition having peroxynitrite scavenging activity using as an active ingredient gondalbi extract or fractions thereof, or compounds derived therefrom.

세계적으로 식생활과 생활수준의 향상 및 스트레스로 인해 비만이 증가하고 있으며 비만은 당뇨병, 동맥경화 등 다른 질환으로 발전할 수 있기 때문에 최근 사회문제화 되고 있다. 비만을 감소시키기 위하여 약물요법, 식이요법, 수술요법 등이 강구되고 있으며, 식이요법의 일환으로 산채류를 이용하여 비만 이외에도 당뇨병 및 동맥경화 등 질환을 예방 및 치유하기 위해 노력하고 있다(Jeong et al., 2006). 산채류는 비타민, 섬유질, 항산화물질 등을 많이 함유하기 때문에 비만 및 비만 관련 질환의 치료를 위해 사용하고 있는 것으로 생각된다. 본 발명자들도 산마늘(Allium victorialis)(Choi et al., 2005) 누룩치(Pleurospermum kamtschaticum)(Jung et al., 2007), 및 해당화(Rosa rugosa)의 뿌리((Park et al., 2005))의 항비만 효과를 보고한 바 있다.
Obesity is increasing due to the improvement of diet, living standards and stress all over the world, and obesity has become a social problem recently because it can develop into other diseases such as diabetes and arteriosclerosis. In order to reduce obesity, drug therapy, dietary therapy, surgical therapy, etc. are being taken, and as part of the diet, wild vegetables are used to prevent and cure diseases such as diabetes and arteriosclerosis in addition to obesity (Jeong et al. , 2006). Wild vegetables are considered to be used for the treatment of obesity and obesity-related diseases because they contain a lot of vitamins, fiber, antioxidants and the like. The inventors also found Allium victorialis (Choi et al., 2005) Pleurospermum kamtschaticum (Jung et al., 2007), and the roots of Rosa rugosa ((Park et al., 2005). ) Has reported an anti-obesity effect.

퍼옥시니트라이트(peroxinitrite, ONOO-)는 수퍼옥사이드 음이온 라디컬(·O2 -)과 일산화질소(NO)의 반응 결과 생성되는 것으로서 세포에 심각한 손상을 끼치는 요인 중 하나다(Radi et al., 1991). 이것은 단백질 및 지질의 과산화를 유도하고 세포독성을 일으키고 나아가 급속한 신경손상을 일으킨다(Haenen et al., 1997). 그뿐 아니라 퍼옥시니트라이트는 동맥경화, 당뇨병, 비만, 고콜레스테롤증등 대사성 질환이나 순환기성 질환 유발효과를 나타낸다고 보고되고 있다(Korda et al., 2008; Patcher et al., 2005; Drel et al., 2007).
Peroxy nitrite (peroxinitrite, ONOO -) - is one of the factors that the reaction result severe damage to the cells as being generated between the nitrogen monoxide (NO) (Radi et al, the superoxide anion radical (· O 2). 1991). This induces peroxidation of proteins and lipids, results in cytotoxicity and further rapid neuronal damage (Haenen et al., 1997). In addition, peroxynitrite has been reported to cause metabolic or circulatory diseases such as atherosclerosis, diabetes, obesity, hypercholesterolemia (Korda et al., 2008; Patcher et al., 2005; Drel et al., 2007).

한국에서 곤달비(Ligularia stenocephala)는 국화과에 속하는 산채류로서 애용되고, 특히 육식을 할 때 병행하여 함께 먹는 산채류이기도 하다. 곤달비의 항혈전효과가 이미 보고되어 있지만 항비만 효과에 대해서는 보고된 바 없다. 곤달비에 포함되는 활성성분 중 곤달비의 뿌리에서는 ligulariacephalins A, B, C, 5,6-dimethoxy-2-isopropylbenzofuran, euparin, (R)-(-)-hydroxytremetone 등(Toyoda et al., 2005)이 분리된 바 있고, 곤달비 잎에는 항혈전 성분으로서 3,4-dicaffeoydicquinic acid와 3,5-dicaffeoylquinic acid이 포함되어 있음이 알려져 있다(Yoon et al., 2008). 그러나 3,4-dicaffeoydicquinic acid와 3,5-dicaffeoylquinic acid 외에 곤달비에 포함되어 있는 카페오일퀴닌산류 화합물 종류에 대해서는 밝혀진 바가 없다. 상기 카페오일퀴닌산류 화합물의 항산화작용, 항염활성, 항미생물작용, 혈관확장작용, 간세포보호작용,및 혈소판응집억제작용 등에 대해서 보고된바 있다(Zhao et al., 2006).
In Korea, Ligularia stenocephala is used as a wild vegetable belonging to the Asteraceae family, and it is also a wild vegetable eaten in parallel when eating meat. Anti-thrombotic effects of gondal have been reported, but no anti-obesity effects have been reported. Ligulariacephalins A, B, C, 5,6-dimethoxy-2-isopropylbenzofuran, euparin, (R)-(-)-hydroxytremetone, etc. (Toyoda et al., 2005) It is known that gondal leaf contains 3,4-dicaffeoydicquinic acid and 3,5-dicaffeoylquinic acid as antithrombotic components (Yoon et al., 2008). However, in addition to the 3,4-dicaffeoydicquinic acid and 3,5-dicaffeoylquinic acid, the types of caffeoylquininic acid compounds included in gondal are unknown. Antioxidant activity, anti-inflammatory activity, antimicrobial action, vasodilator action, hepatocyte protection action, and platelet aggregation inhibitory action of the caffeoylquinine acid compounds have been reported (Zhao et al., 2006).

본 발명자들은 퍼옥시니트라이트를 소거하는 산채를 스크리닝하던 중 곤달비 메탄올 추출물에 퍼옥시니트라이트를 소거하는 탁월한 효과가 있음을 발견하고 이를 에테르 및 부탄올로 분획하고 그 주요 활성성분을 분석하였다. 그 결과, 곤달비 메탄올 추출물, 이의 분획물, 및 이의 주요 활성성분인 6종의 카페오일퀴닌산류 화합물에 항비만효과가 있음을 확인하고 본 발명을 완성하였다.
The inventors found that while screening wild vegetables for scavenging peroxynitrite, the gondalbi methanol extract had an excellent effect of scavenging peroxynitrite and fractionating it with ether and butanol and analyzing its main active ingredient. As a result, it was confirmed that there is an anti-obesity effect on gondal methanol extract, fractions thereof, and six kinds of caffeoylquinine acid compounds which are main active ingredients thereof, and completed the present invention.

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본 발명의 목적은 곤달비(Ligularia stenocephala) 추출물, 이의 분획물, 또는 이로부터 분리한 화합물을 유효성분으로 함유하는 비만 관련 질환 예방 또는 치료용 조성물을 제공하는 것이다. An object of the present invention is to provide a composition for the prevention or treatment of obesity-related diseases containing Ligularia stenocephala extract, fractions thereof, or compounds isolated therefrom as an active ingredient.

본 발명의 목적은 상기 조성물을 포함하는 함유하는 비만 관련 질환의 예방 또는 치료용 약학 조성물을 제공하는 것이다. An object of the present invention is to provide a pharmaceutical composition for the prevention or treatment of obesity-related diseases containing the composition.

본 발명의 목적은 상기 조성물을 포함하는 함유하는 비만 관련 질환의 예방 또는 개선용 식품 조성물을 제공하는 것이다. An object of the present invention is to provide a food composition for the prevention or improvement of obesity-related diseases containing the composition.

본 발명의 목적은 상기 조성물을 포함하는 함유하는 비만 관련 질환의 예방 또는 개선용 화장료 조성물을 제공하는 것이다. An object of the present invention to provide a cosmetic composition for the prevention or improvement of obesity-related diseases containing the composition.

본 발명의 목적은 상기 조성물을 포함하는 함유하는 비만 관련 질환의 예방 또는 개선용 의약외품 조성물을 제공하는 것이다. An object of the present invention is to provide a quasi-drug composition for the prevention or improvement of obesity-related diseases containing the composition.

본 발명의 목적은 3,4-di-O-caffeoylquinic acid(3,4-DQ), 3,5-di-O-dicaffeoyl-epi-quinic acid(3,5-DeQ), 3,5-di-O-caffeoylquinic acid(3,5-DQ), 4,5-di-O-caffeoylquinic acid(4,5-DQ), 5-O-caffeoylquinic acid(5-CQ) 및 3-O-caffeoylquinic acid(3-CQ)로 이루어진 군으로부터 선택되는 1 종 이상의 화합물 또는 이들의 이의 약제학적으로 허용되는 염을 유효성분으로 함유하는 비만 관련 질환 예방 또는 치료용 조성물을 제공하는 것이다.
An object of the present invention is 3,4-di-O-caffeoylquinic acid (3,4-DQ), 3,5-di- O -dicaffeoyl- epi -quinic acid (3,5-DeQ), 3,5-di O- caffeoylquinic acid (3,5-DQ), 4,5-di-O-caffeoylquinic acid (4,5-DQ), 5- O -caffeoylquinic acid (5-CQ) and 3- O -caffeoylquinic acid ( It is to provide a composition for the prevention or treatment of obesity-related diseases containing at least one compound selected from the group consisting of 3-CQ or a pharmaceutically acceptable salt thereof as an active ingredient.

상기 목적을 달성하기 위하여, 본 발명은 곤달비(Ligularia stenocephala) 추출물, 이의 분획물, 또는 이로부터 분리한 화합물을 유효성분으로 함유하는 퍼옥시니트라이트 소거 활성을 갖는 조성물을 제공한다.
In order to achieve the above object, the present invention is a gonadabi ( Ligularia Stenocephala ) provides a composition having a peroxynitrite scavenging activity containing an extract, a fraction thereof, or a compound separated therefrom as an active ingredient.

본 발명자들은 곤달비 메탄올 추출물, 이의 분획물에 퍼옥시니트라이트를 소거하는 탁월한 효과가 있음을 발견하고 이들의 그 주요 활성성분을 분석함으로써 곤달비 메탄올 추출물, 이의 분획물, 및 이의 주요 활성성분인 6종의 카페오일퀴닌산류 화합물에 항비만효과가 있음을 확인하였다.
The present inventors have found that there is an excellent effect of eliminating peroxynitrite on the gondal methanol extract, fractions thereof, and analyzing the main active ingredients thereof, the gondal methanol extract, fractions thereof, and six main cafes thereof. It was confirmed that the anti-obesity effect on the oil quinic acid compounds.

본 발명에서 사용되는 용어, "퍼옥시니트라이트(peroxinitrite, ONOO-) 소거 활성"은 수퍼옥사이드 음이온 라디컬(·O2 -)과 질산(NO)의 반응에 따라 퍼옥시니트라이트가 생성되는 것을 차단 또는 그 효율을 감소시키거나 생성된 퍼옥시니트라이트를 제거 또는 감소시키는 것을 말한다. 일반적으로 비만증에서 고렙틴혈증(hyperleptinemia)이 나타나고 그 결과 퍼옥시니트라이트가 증가한다. 이런 일산화질소/퍼옥시니트라이트 불균형 때문에 동맥경화와 당뇨병 질환이 발생될 수 있으므로 퍼옥시니트라이트 존부가 비만 관련 질환의 중요한 지표가 된다.
As used herein, the term "peroxy nitrite (peroxinitrite, ONOO -) scavenging activity" is superoxide anion radical (· O 2 -) to be a peroxy nitrite is produced by the reaction of the acid and nitric acid (NO) It means blocking or reducing its efficiency or removing or reducing the peroxynitrite produced. In general, hyperleptinemia develops in obesity, resulting in an increase in peroxynitrite. This nitric oxide / peroxynitrite imbalance can lead to atherosclerosis and diabetes mellitus, so the presence of peroxynitrite is an important indicator of obesity-related diseases.

본 발명의 구체적인 실시예에 따르면, 본 발명자들은 곤달비 추출물의 퍼옥시니트라이트 소거 활성 효과를 확인하였으며 보다 구체적으로, 곤달비 추출물로부터 퍼옥시니트라이트 소거효과 실험을 한 결과 그 IC50 값이 0.87 ± 0.33 μg/ml이었다. 이 값은 양성 대조화합물인 페니실라민(penicillamine)의 IC50 값 0.89 ± 0.22 μg/ml 와 비슷한 값으로 곤달비 메탄올 추출물이 매우 강한 퍼옥시니트라이트 소거 활성을 가짐을 알 수 있었다(도 3).
According to a specific embodiment of the present invention, the present inventors confirmed the peroxynitrite scavenging effect of the gondalby extract, and more specifically, the result of the peroxynitrite scavenging effect experiment from the gondalbi extract, the IC 50 value of 0.87 ± 0.33 μg / ml. This value was similar to the IC 50 value of 0.89 ± 0.22 μg / ml of penicillamine, a positive control compound, indicating that the gondal methanol extract had a very strong peroxynitrite scavenging activity (FIG. 3).

아울러, 본 발명자들은 퍼옥시니트라이트가 비만 관련 질환의 원인이 되며, 곤달비 추출물 및 분획물은 이러한 퍼옥시니트라이트 소거 활성을 가짐으로써 궁극적으로 비만 관련 질환의 예방 또는 치료 효과가 있음을 확인하였다.
In addition, the present inventors confirmed that peroxynitrite causes obesity-related diseases, and gondalby extracts and fractions have such peroxynitrite scavenging activity, thereby ultimately preventing or treating obesity-related diseases.

상기 비만 관련 질환에는 퍼옥시니트라이트가 증가되어 산화질소/퍼옥시니트라이트(NO/peroxynitrite) 불균형이 일어나는 것을 원인으로 발병하는 질환으로 예를 들어 비만, 고지혈증 또는 대사 증후군이 포함되나 이에 제한되지 않는다. The obesity-related disorders include, but are not limited to, obesity, hyperlipidemia, or metabolic syndrome, which are caused by an increase in peroxynitrite resulting in a nitrogen oxide / peroxynitrite imbalance. .

본 발명의 구체적인 실시예에 따르면, 본 발명자들은 항비만활성 측정을 위해 비만 랫트에 곤달비 메탄올 추출물과 그 분획물인 에테르 분획물, 부탄올 분획물을 투여하면 체중(도 4)과 복부 지방조직(후복강 및 부고환)의 무게(도 5)가 장상군 수준으로 유의성있게 감소하고, 총 콜레스테롤 함량과 LDL-콜레스테롤의 함량을 감소하고 동맥경화지수(A.I.)를 감소시켰으며(표 3), 및 항산화 활성을 현저히 감소함을 알아냈다(표 4).
According to a specific embodiment of the present invention, the present inventors administered weight (Fig. 4) and abdominal adipose tissue (epithelial cavity and epididymis when administering the gondabi methanol extract and its fraction ether fraction, butanol fraction to obese rats for anti-obesity activity measurement ) Weight (FIG. 5) significantly decreased to the level of the intestinal group, decreased total cholesterol content and LDL-cholesterol content, decreased arteriosclerosis index (AI) (Table 3), and significantly reduced antioxidant activity. (Table 4).

본 발명에서, 곤달비 추출물은 곤달비를 세척하고 건조시킨 후 분쇄하는 단계; 및 상기 분쇄된 곤달비를 물, C1~C4의 저급 알콜 또는 이들의 혼합용매로부터 선택된 용매로 추출하여 수득할 수 있다. In the present invention, the gondalby extract is crushed after washing and drying the gondalby; And the ground gondal ratio can be obtained by extracting with a solvent selected from water, C 1 ~ C 4 lower alcohol or a mixed solvent thereof.

상기 곤달비 추출물은 물, C1~C4의 저급 알콜 및 이들의 혼합 용매로 구성되는 군으로부터 선택되는 용매, 바람직하게는 메탄올로 추출한 것을 포함한다. 또한, 본 발명에 있어서, 상기 추출물에는, 추출처리에 의해 얻어지는 추출액, 추출액의 희석액 또는 농축액, 추출액을 건조하여 얻어지는 건조물, 또는 이들 조정제물 또는 정제물 중 어느 하나도 포함하는 것으로 한다. 추출 방법은 특별히 제한되지 않고, 유효 성분이 파괴되지 않거나 최소화된 조건에서 실온 또는 가온하여 추출할 수 있다. 보다 구체적으로, 본 발명에서 곤달비 추출물을 얻기 위한 방법은 다음과 같다. 곤달비 분쇄물을 건조 중량의 약 2 내지 20배, 바람직하게는 약 3 내지 5배에 달하는 부피의 물, 메탄올, 에탄올 및 부탄올 등과 같은 C1~C4의 저급 알콜의 극성 용매 또는 이들의 약 1:0.1 내지 1:10의 혼합비를 갖는 혼합용매를 용출 용매로써 사용하고, 추출 온도는 20 내지 100℃, 바람직하게는 80℃에서, 추출 기간은 약 5시간 내지 10일, 바람직하게는 5-10 시간 동안 열수 추출, 냉침 추출, 환류 냉각 추출 또는 초음파 추출 등의 추출방법을 사용하여 추출한다. 바람직하게는 환류 추출로 1회 내지 5회 연속 추출하여 감압여과하고, 그 여과추출물을 증류농축장치로 20 내지 100℃, 바람직하게는 실온에서 감압농축하여 물, 저급 알콜 또는 이들의 혼합용매에 가용한 곤달비 조추출물을 수득할 수 있다. The gondalby extract comprises a solvent selected from the group consisting of water, lower alcohols of C 1 to C 4 and mixed solvents thereof, preferably extracted with methanol. In addition, in this invention, the said extract shall contain the extract obtained by an extraction process, the dilution or concentrate of an extract, the dried material obtained by drying an extract, or any of these modifiers or refined products. The extraction method is not particularly limited and may be extracted at room temperature or warmed under conditions where the active ingredient is not destroyed or minimized. More specifically, the method for obtaining gondal extract in the present invention is as follows. The gondalby pulverized product is prepared by using a polar solvent of C 1 to C 4 lower alcohols such as water, methanol, ethanol and butanol, etc., in volume of about 2 to 20 times, preferably about 3 to 5 times, dry weight or about 1 thereof. A mixed solvent having a mixing ratio of: 0.1 to 1:10 is used as the elution solvent, and the extraction temperature is 20 to 100 ° C, preferably 80 ° C, and the extraction period is about 5 hours to 10 days, preferably 5-10 Extraction is performed using extraction methods such as hot water extraction, cold needle extraction, reflux cooling extraction or ultrasonic extraction for a period of time. Preferably, the mixture is extracted at 1 to 5 times by reflux extraction and filtered under reduced pressure, and the filtrate is concentrated under reduced pressure at a temperature of 20 to 100 ° C., preferably at room temperature with a distillation concentrator, and soluble in water, lower alcohols or a mixed solvent thereof. One gondal ratio crude extract can be obtained.

곤달비 추출물은 천연, 잡종, 변종 식물의 다양한 기관으로부터 추출될 수 있고, 예를 들어 뿌리, 줄기, 잎, 및 꽃뿐만 아니라 식물 조직 배양물로부터 추출 가능하며 곤달비의 잎에서 추출하는 것이 가장 바람직하다. 본 발명의 구체적인 실시예에 따르면 곤달비의 잎으로부터 곤달비 추출물을 제조하였다.
The gondalby extract can be extracted from various organs of natural, hybrid, and variegated plants, for example from roots, stems, leaves, and flowers, as well as from plant tissue cultures, most preferably from the leaves of gondal. According to a specific embodiment of the present invention was prepared gondalby extract from the leaves of gondalby.

본 발명에서, 본 발명의 곤달비 추출물의 분획물은 곤달비를 세척하고 건조시킨 후 분쇄기로 분쇄하는 단계; 상기 분쇄된 곤달비를 물, C1~C4의 저급 알콜 또는 이들의 혼합용매로부터 선택된 용매로 추출하여 곤달비 추출물을 얻는 단계; 및 상기 곤달비 추출물을 에테르, 부탄올, 물로 구성되는 군으로부터 선택되는 1 종 이상의 용액으로 분획하는 단계를 포함하여 제조한다. In the present invention, the fraction of gondalbi extract of the present invention is the step of washing and drying the gondalbi pulverized with a grinder; Extracting the pulverized gondal ratio with a solvent selected from water, a lower alcohol having 1 to 4 C, or a mixed solvent thereof to obtain a gondal ratio extract; And fractionating the gondalby extract into one or more solutions selected from the group consisting of ether, butanol, and water.

보다 구체적으로 곤달비 추출물의 용매 분획물은 곤달비 추출물을 물로 현탁한 후 에테르 또는 부탄올 등과 같은 용매를 사용하여 분획함으로써 극성 용매 분획물과 비극성 용매 분획물을 각각 수득할 수 있다. 본 발명에서, 구체적인 일 양태로서 용매 분획물로는 에테르 분획물 또는 부탄올 분획물이 제공된다.More specifically, the solvent fraction of the gondalby extract may be obtained by suspending the gondalby extract with water and then fractionating it with a solvent such as ether or butanol to obtain a polar solvent fraction and a nonpolar solvent fraction, respectively. In a specific aspect of the present invention, the solvent fraction is provided with an ether fraction or butanol fraction.

본 발명에서 곤달비 추출물의 분획물을 얻기 위한 방법은 다음과 같다. 상기에서 얻은 곤달비 조추출물을 물에 현탁한 후, 현탁액의 약 1 내지 100배, 바람직하게는 약 1 내지 5배 부피의 에테르과 같은 비극성 용매를 가하여 1회 내지 10회, 바람직하게는 2회 내지 5회에 걸쳐 비극성 용매 가용층을 추출, 분리하여 수득할 수 있다. 또한 추가로 통상의 분획 공정을 수행할 수도 있다(Harborne J.B. Phytochemical methods: A guide to modern techniques of plant analysis , 3rd Ed. p6-7, 1998). 구체적으로, 상기 곤달비 조추출물을 물에 현탁한 후, 에테르를 혼합한 후 분획하여 에테르 분획물을 수득할 수 있으며, 이 에테르 분획물에 부탄올을 가하여 부탄올 분획물을 수득할 수 있다.
Method for obtaining a fraction of gondalby extract in the present invention is as follows. The obtained gondal ratio crude extract is suspended in water, and then added to a nonpolar solvent such as an ether of about 1 to 100 times, preferably about 1 to 5 times the volume of the suspension, 1 to 10 times, preferably 2 to 5 times. It can be obtained by extracting and separating the nonpolar solvent soluble layer over times. It is also possible to further carry out conventional fractionation processes (Harborne JB Phytochemical methods: A guide to modern techniques of plant analysis , 3rd Ed. p6-7, 1998). Specifically, the gondal ratio crude extract is suspended in water and then ether mixed and fractionated to obtain an ether fraction. Butanol fraction may be obtained by adding butanol to the ether fraction.

또한, 본 발명자들은 추가적으로 상기 곤달비 추출물 및 이의 분획물 중 특히 항비만 효과를 나타내는 유효 성분을 밝히고자 하였다. 유효 성분은 상기 추출물 또는 분획물에 대해 크로마토그래피를 1회 이상 순차적으로 수행함으로써 분리할 수 있으며, 크로마토그래의 컬럼의 종류와 전개 용매는 다양하게 조절될 수 있다. 본 발명의 구체적인 실시예에서는 유효성분 분석을 위해 곤달비 추출물 및 이의 분획물의 고성능액체크로마토그래피(HPLC) 분석을 수행하였다. Lactuca indica에서 분리된 카페오일퀴닌산 유도체들을 표준품으로 이용하여 곤달비 내 카페오일퀴닌산 유도체들의 종류 및 함량을 측정하고 곤달비 추출물 및 분획물 중 카페오일퀴닌산 유도체들의 함량 등을 측정하였다. 그 결과, 표준폼과의 비교에 의해 곤달비에는 3,4-di-O-caffeoylquinic acid(3,4-DQ), 3,5-di-O-dicaffeoyl-epi-quinic acid(3,5-DeQ), 3,5-di-O-caffeoylquinic acid(3,5-DQ), 4,5-di-O-caffeoylquinic acid(4,5-DQ), 5-O-caffeoylquinic acid(5-CQ), 3-O-caffeoylquinic acid(3-CQ)이 함유되었음이 확인되었다. 그러나 곤달비에서 표준폼 중의 3-O-p-coumaroyl-caffeoylquinic acid(3-pCQ)는 검출되지 않았다. In addition, the present inventors additionally sought to identify the active ingredient exhibiting an anti-obesity effect among the gondal extract and its fractions. The active ingredient may be separated by performing chromatography one or more times sequentially on the extract or fraction, and the type and developing solvent of the column of the chromatograph may be controlled in various ways. In a specific embodiment of the present invention, high-performance liquid chromatography (HPLC) analysis of gondal extract and fractions thereof was performed for active ingredient analysis. Lactuca Using the caffeyl quinquinate derivatives isolated from indica as standard products, the types and contents of caffeyl quinquinate derivatives in gondabi were measured, and the contents of caffeyl quinquinate derivatives in the gondabi extract and fractions were measured. As a result, by comparison with a standard foam gondalbi include 3,4-di-O-caffeoylquinic acid (3,4-DQ), 3,5-di- O -dicaffeoyl- epi -quinic acid (3,5-DeQ ), 3,5-di- O -caffeoylquinic acid (3,5-DQ), 4,5-di-O-caffeoylquinic acid (4,5-DQ), 5- O -caffeoylquinic acid (5-CQ), It was confirmed that 3- O -caffeoylquinic acid (3-CQ) was contained. However, 3- O - p- coumaroyl-caffeoylquinic acid (3-pCQ) in standard foam was not detected in gondal ratio.

이에 본 발명에서는, 곤달비를 세척하고 건조시킨 후 분쇄기로 분쇄하는 단계; 상기 분쇄된 곤달비를 물, C1~C4의 저급 알콜 또는 이들의 혼합용매로부터 선택된 용매로 추출하여 곤달비 추출물을 얻는 단계; 상기 곤달비 추출물을 에테르, 부탄올, 물로 구성되는 군으로부터 선택되는 1 종 이상의 용액으로 분획하여 곤달비의 에테르, 부탄올 또는 물 분획물을 얻는 단계; 및 상기 분획물을 고성능액체크로마토그래피를 수행하여 3,4-di-O-caffeoylquinic acid(3,4-DQ), 3,5-di-O-dicaffeoyl-epi-quinic acid(3,5-DeQ), 3,5-di-O-caffeoylquinic acid(3,5-DQ), 4,5-di-O-caffeoylquinic acid(4,5-DQ), 5-O-caffeoylquinic acid(5-CQ) 및 3-O-caffeoylquinic acid(3-CQ)로 이루어진 군으로부터 선택되는 1 종 이상의 화합물을 얻는 단계를 포함하는 곤달비로부터 분리한 3,4-di-O-caffeoylquinic acid(3,4-DQ), 3,5-di-O-dicaffeoyl-epi-quinic acid(3,5-DeQ), 3,5-di-O-caffeoylquinic acid(3,5-DQ), 4,5-di-O-caffeoylquinic acid(4,5-DQ), 5-O-caffeoylquinic acid(5-CQ) 및 3-O-caffeoylquinic acid(3-CQ)로 이루어진 군으로부터 선택되는 1 종 이상의 화합물 제조방법을 제공한다.
Therefore, in the present invention, washing and drying the gondal ratio and pulverizing with a grinder; Extracting the pulverized gondal ratio with a solvent selected from water, a lower alcohol having 1 to 4 C, or a mixed solvent thereof to obtain a gondal ratio extract; Fractionating the gondalby extract with one or more solutions selected from the group consisting of ether, butanol, and water to obtain ether, butanol or water fractions of gondalby; And the fraction of high-performance liquid chromatography carried out by a 3,4-di-O-caffeoylquinic acid (3,4-DQ), 3,5-di- O -dicaffeoyl- epi -quinic acid (3,5-DeQ) , 3,5-di- O -caffeoylquinic acid (3,5-DQ), 4,5-di-O-caffeoylquinic acid (4,5-DQ), 5- O -caffeoylquinic acid (5-CQ) and 3 3,4-di-O-caffeoylquinic acid (3,4-DQ), 3, isolated from gondalby comprising obtaining at least one compound selected from the group consisting of O- caffeoylquinic acid (3-CQ). 5-di- O -dicaffeoyl- epi -quinic acid (3,5-DeQ), 3,5-di- O -caffeoylquinic acid (3,5-DQ), 4,5-di-O-caffeoylquinic acid (4 , 5-DQ), 5- O- caffeoylquinic acid (5-CQ), and 3- O- caffeoylquinic acid (3-CQ).

상기 6종의 카페오일퀴닌산 유도체들의 화학식은 하기와 같다. Chemical formulas of the six kinds of caffeoylquinic acid derivatives are as follows.

Figure 112010006567818-pat00001
Figure 112010006567818-pat00001

상기 6종의 카페오일퀴닌산 유도체들은 천연물질, 바람직하게 상기 곤달비로부터 분리할 수 있고, 곤달비 추출물은 상기 언급한 바와 같이 천연, 잡종, 변종 식물의 다양한 기관으로부터 분리될 수 있으며 곤달비 잎로부터 추출하는 것이 가장 바람직하다. 또한, 이들 6종의 카페오일퀴닌산 유도체들은 당 분야의 공지된 방법으로 화학적 합성법에 의해 제조될 수도 있다.
The six kinds of caffeoylquininic acid derivatives can be separated from natural substances, preferably the gondalbi, and the gondalbi extract can be separated from various organs of natural, hybrid, and variegated plants as mentioned above, and extracted from gondalbi leaves. Most preferred. In addition, these six caffeoylquinolinic acid derivatives may be prepared by chemical synthesis by methods known in the art.

본 발명에서 사용되는 용어, "약제학적으로 허용 가능한 염"은 통상적인 방법으로 제조한 염을 의미하며, 당업자에게 공지되어 있다. "약제학적으로 허용 가능한 염" 은 약리학적 또는 생리학적으로 허용되는 다음 무기산과 유기산 및 염기로부터 유도된 염을 포함하지만 이것으로 한정되지는 않는다. 적합한 산의 예로는 염산, 브롬산, 황산, 질산, 과염소산, 푸마르산, 말레산, 인산, 글리콜산, 락트산, 살리실산, 숙신산, 톨루엔-p-설폰산, 타르타르산, 아세트산, 시트르산, 메탄설폰산, 포름산, 벤조산, 말론산, 나프탈렌-2-설폰산, 벤젠설폰산 등을 포함할 수 있다. 적합한 염기로부터 유도된 염은 알칼리 금속, 예를 들어, 나트륨, 알칼리코금속, 예를 들어, 마그네슘, 암모늄 등을 포함할 수 있다.
As used herein, the term "pharmaceutically acceptable salts" refers to salts prepared by conventional methods and known to those skilled in the art. "Pharmaceutically acceptable salts" include, but are not limited to, salts derived from the following pharmacologically or physiologically acceptable inorganic and organic acids and bases. Examples of suitable acids include hydrochloric acid, bromic acid, sulfuric acid, nitric acid, perchloric acid, fumaric acid, maleic acid, phosphoric acid, glycolic acid, lactic acid, salicylic acid, succinic acid, toluene-p-sulfonic acid, tartaric acid, acetic acid, citric acid, methanesulfonic acid, formic acid , Benzoic acid, malonic acid, naphthalene-2-sulfonic acid, benzenesulfonic acid, and the like. Salts derived from suitable bases may include alkali metals such as sodium, alkali cometals such as magnesium, ammonium and the like.

상기 곤달비 추출물, 이의 분획물 및 이로부터 분리한 4-di-O-caffeoylquinic acid(3,4-DQ), 3,5-di-O-dicaffeoyl-epi-quinic acid(3,5-DeQ), 3,5-di-O-caffeoylquinic acid(3,5-DQ), 4,5-di-O-caffeoylquinic acid(4,5-DQ), 5-O-caffeoylquinic acid(5-CQ) 및 3-O-caffeoylquinic acid(3-CQ)은 인공적으로 합성된 화합물이 아니라 천연 추출물로부터 획득한 성분을 기초로 하므로 안전하고 독성, 부작용이 거의 없으므로 장기간의 복용이 가능하다는 장점이 있다. 또한, 상기 조성물은 인간뿐만 아니라, 비만 관련 질환이 발생될 수 있는 소, 개 등의 동물에게 사용될 수도 있다.
The gondalbi extract, 4-di-O-caffeoylquinic acid (3,4-DQ) was separated fractions thereof and therefrom, 3,5-di- O -dicaffeoyl- epi -quinic acid (3,5-DeQ), 3 , 5-di- O -caffeoylquinic acid (3,5-DQ), 4,5-di-O-caffeoylquinic acid (4,5-DQ), 5- O -caffeoylquinic acid (5-CQ) and 3- O -Caffeoylquinic acid (3-CQ) is based on ingredients obtained from natural extracts, not artificially synthesized compounds, so it is safe, toxic, and has no side effects. In addition, the composition may be used not only in humans, but also in animals such as cattle, dogs, and the like, in which obesity-related diseases may occur.

이상의 6종의 caffeoylquinic acid 화합물들이 곤달비 메탄올 추출물 중 약 67.8%, 부탄올 분획물 중 약 94.52%의 함유량을 보여 매우 높은 함량으로 함유되어 있음을 알 수 있었다(표 2). 따라서, 곤달비 추출물 및 분획물이 우수한 항비만활성을 가지며, 이들의 주요 성분인 활성물질 4-di-O-caffeoylquinic acid(3,4-DQ), 3,5-di-O-dicaffeoyl-epi-quinic acid(3,5-DeQ), 3,5-di-O-caffeoylquinic acid(3,5-DQ), 4,5-di-O-caffeoylquinic acid(4,5-DQ), 5-O-caffeoylquinic acid(5-CQ), 3-O-caffeoylquinic acid(3-CQ) 역시 동일하게 항비만활성을 가질 것으로 충분히 예측할 수 있다.
The six caffeoylquinic acid compounds contained about 67.8% in the Gondalbi methanol extract and about 94.52% in the butanol fraction, indicating a very high content (Table 2). Thus, gondalbi extracts and fractions have excellent anti-obesity activity, and their active ingredients 4-di-O-caffeoylquinic acid (3,4-DQ), 3,5-di- O -dicaffeoyl- epi- quinic acid (3,5-DeQ), 3,5-di- O -caffeoylquinic acid (3,5-DQ), 4,5-di-O-caffeoylquinic acid (4,5-DQ), 5- O -caffeoylquinic acid (5-CQ) and 3- O- caffeoylquinic acid (3-CQ) can also be expected to have the same anti-obesity activity.

그러므로 곤달비 추출물, 이의 분획물 및 4-di-O-caffeoylquinic acid(3,4-DQ), 3,5-di-O-dicaffeoyl-epi-quinic acid(3,5-DeQ), 3,5-di-O-caffeoylquinic acid(3,5-DQ), 4,5-di-O-caffeoylquinic acid(4,5-DQ), 5-O-caffeoylquinic acid(5-CQ), 3-O-caffeoylquinic acid(3-CQ)은 비만 관련 질환에 대한 우수한 예방 및 치료 활성을 갖는바, 본 발명은 상기 6종의 카페오일퀴닌산 유도체 또는 이의 약제학적으로 허용가능한 염을 유효성분으로 포함하는 비만 관련 질환의 예방 또는 치료용 약학 조성물을 제공한다.
Therefore gondalbi extract, fractions thereof, and 4-di-O-caffeoylquinic acid (3,4-DQ), 3,5-di- O -dicaffeoyl- epi -quinic acid (3,5-DeQ), 3,5-di O- caffeoylquinic acid (3,5-DQ), 4,5-di-O-caffeoylquinic acid (4,5-DQ), 5- O -caffeoylquinic acid (5-CQ), 3- O -caffeoylquinic acid ( 3-CQ) has excellent prophylactic and therapeutic activity against obesity-related diseases, and the present invention provides the prevention of obesity-related diseases comprising the six kinds of caffeoylquinolinic acid derivatives or pharmaceutically acceptable salts thereof as an active ingredient. Or it provides a pharmaceutical composition for treatment.

본 발명의 곤달비 추출물, 이의 분획물 및 이로부터 분리한 6종의 카페오일퀴닌산 유도체 또는 그의 약제학적으로 허용 가능한 염은 우수한 퍼옥시니트라이트(peroxinitrite, ONOO-) 소거 활성을 가지고 비만 랫트의 체중, 복부 지방 조직 및 동맥경화 지수를 감소시키고 TBARS, 하이드록시 라디컬 수치 및 SOD 활성 수치를 효과적으로 억제하므로 비만 관련 질환의 예방 및 치료에 효과적이므로 비만 관련 질환 예방 및 치료용 약학 조성물로 사용될 수 있다.
Gondalbi extract of the present invention, fractions thereof, and six kinds of caffeoylquinolinic acid derivatives isolated therefrom, or pharmaceutically acceptable salts thereof, have excellent peroxitrite (ONOO − ) scavenging activity and have weight of obese rats, Since it reduces abdominal adipose tissue and atherosclerosis index and effectively inhibits TBARS, hydroxy radical level and SOD activity level, it is effective for the prevention and treatment of obesity related diseases, and thus can be used as a pharmaceutical composition for preventing and treating obesity related diseases.

본 발명에서 사용되는 용어, "예방"은 곤달비 추출물, 이의 분획물 및 이로부터 분리한 6종의 카페오일퀴닌산 유도체를 포함하는 조성물의 투여로 상기 질환의 발병을 억제 또는 지연시키는 모든 행위를 말한다. As used herein, the term "prevention" refers to any action that inhibits or delays the onset of the disease by administration of a composition comprising a gondal extract, a fraction thereof, and six caffeoylquininic acid derivatives isolated therefrom.

본 발명에서 사용되는 용어, "치료"는 곤달비 추출물, 이의 분획물 및 이로부터 분리한 6종의 카페오일퀴닌산 유도체를 포함하는 조성물의 투여로 상기 질환의 증세가 호전되거나 이롭게 변경하는 모든 행위를 말한다.
As used herein, the term "treatment" refers to all actions of improving or beneficially modifying the symptoms of the disease by administration of a composition comprising a gondal extract, a fraction thereof, and six kinds of caffeoylquininic acid derivatives isolated therefrom. .

본 발명에 따른 조성물은 쥐, 생쥐, 가축, 인간 등의 포유동물에 다양한 경로로 투여될 수 있다. 투여의 모든 방식은 예상될 수 있고, 예를 들어, 경구, 직장 또는 정맥, 근육, 피하, 자궁내 경막 또는 뇌혈관내(intracerebroventricular) 주사에 의하여 투여될 수 있다.
The composition according to the present invention can be administered to mammals such as rats, mice, livestock, humans, etc. by various routes. All modes of administration can be expected and can be administered, for example, by oral, rectal or intravenous, intramuscular, subcutaneous, intrauterine dural or intracerebroventricular injection.

본 발명에서 사용되는 비만 관련 질환 예방 및 치료용 약학 조성물의 처리량은 약학적으로 유효한 양이어야 한다. 본 발명에서 사용되는 용어, "약학적으로 유효한 양"은 의학적 치료에 적용 가능한 합리적인 수혜/위험 비율로 질환을 치료하기에 충분한 양을 의미하며, 유효 용량 수준은 개체 종류 및 중증도, 연령, 성별, 감염된 바이러스 종류, 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. 유효량은 당업자에게 인식되어 있듯이 처리의 경로, 부형제의 사용 및 다른 약제와 함께 사용할 수 있는 가능성에 따라 변할 수 있다.
The throughput of the pharmaceutical composition for preventing and treating obesity-related diseases used in the present invention should be a pharmaceutically effective amount. As used herein, the term "pharmaceutically effective amount" refers to an amount sufficient to treat a disease at a reasonable benefit / risk ratio applicable to medical treatment, and an effective dose level may refer to an individual type and severity, age, sex, It can be determined according to the type of virus infected, the activity of the drug, the sensitivity to the drug, the time of administration, the route of administration and the rate of release, the duration of treatment, factors including the drug used concurrently, and other factors well known in the medical arts. Effective amounts may vary depending on the route of treatment, the use of excipients, and the possibility of use with other agents, as will be appreciated by those skilled in the art.

본 발명의 비만 관련 질환 예방 및 치료용 약학 조성물의 약학적 처리 형태는 이들의 약제학적으로 허용되는 염의 형태로도 사용될 수 있고, 또한 단독으로 또는 다른 약학적 활성 화합물과 결합뿐만 아니라 적당한 집합으로 사용될 수 있다.
The pharmaceutical treatment forms of the pharmaceutical compositions for the prevention and treatment of obesity-related diseases of the present invention may be used in the form of their pharmaceutically acceptable salts, and may also be used alone or in combination with other pharmaceutically active compounds as well as in a suitable collection. Can be.

본 발명의 비만 관련 질환 예방 및 치료용 약학 조성물은, 포유동물에 투여된 후 활성 성분의 신속, 지속 또는 지연된 방출을 제공할 수 있도록 당업계에 잘 알려진 방법을 사용하여 약학적 제형으로 제조될 수 있다. 제형의 제조에 있어서, 활성 성분을 담체와 함께 혼합 또는 희석하거나, 용기 형태의 담체 내에 봉입시키는 것이 바람직하다.
The pharmaceutical composition for preventing and treating obesity-related diseases of the present invention may be prepared in pharmaceutical formulations using methods well known in the art to provide rapid, sustained or delayed release of the active ingredient after administration to a mammal. have. In the preparation of the formulations, it is preferred that the active ingredient is mixed with or diluted with the carrier, or enclosed in a carrier in the form of a container.

따라서, 본 발명의 비만 관련 질환 예방 및 치료용 약학 조성물은, 통상의 방법에 따라 산제, 과립제, 정제, 캡슐제, 현탁액, 에멀젼, 시럽, 에어로졸 등의 경구형 제형, 외용제, 좌제 및 멸균 주사용액의 형태로 제형화 하여 사용될 수 있고, 조성물의 제조에 통상적으로 사용하는 적절한 담체, 부형제 및 희석제를 더 포함할 수 있다.
Therefore, the pharmaceutical composition for the prevention and treatment of obesity-related diseases of the present invention, powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, oral formulations, external preparations, suppositories, and sterile injectable solutions according to conventional methods It may be used in the form of a formulation, and may further include suitable carriers, excipients and diluents commonly used in the preparation of the composition.

예를 들어, 본 발명의 약학 조성물에 포함될 수 있는 담체, 부형제 및 희석제로는 락토즈, 덱스트로즈, 수크로스, 솔비톨, 만니톨, 자일리톨, 에리스리톨, 말티톨, 전분, 아카시아 고무, 알지네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실리케이트, 셀룰로즈, 메틸 셀룰로즈, 미정질 셀룰로스, 폴리비닐 피롤리돈, 물, 메틸히드록시벤조에이트, 프로필히드록시벤조에이트, 탈크, 마그네슘 스테아레이트 및 광물유를 들 수 있다. 제제화할 경우에는 보통 사용하는 충진제, 증량제, 결합제, 습윤제, 붕해제, 계면활성제 등의 희석제 또는 부형제를 사용하여 조제된다.For example, carriers, excipients and diluents which may be included in the pharmaceutical compositions of the present invention include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium Phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil. In the case of formulation, a diluent or excipient such as a filler, an extender, a binder, a wetting agent, a disintegrant, or a surfactant is usually used.

경구투여를 위한 고형제제에는 정제, 환제, 산제, 과립제, 캡슐제 등이 포함되며, 이러한 고형제제는 상기 화합물에 적어도 하나 이상의 부형제 예를 들어, 전분, 칼슘카보네이트(calcium carbonate), 수크로스(sucrose) 또는 락토오스 (lactose), 젤라틴 등을 섞어 조제된다. 또한 단순한 부형제 이외에 마그네슘 스테아레이트, 탈크같은 윤활제들도 사용된다.Solid preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, and such solid preparations include at least one excipient such as starch, calcium carbonate, sucrose in the compound. Or lactose, gelatin and the like. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used.

경구를 위한 액상 제제로는 현탁제, 내용액제, 유제, 시럽제 등이 해당되고, 흔히 사용되는 단순희석제인 물,리퀴드 파라핀 이외에 여러 가지 부형제, 예를 들어 습윤제, 감미제, 방향제, 보존제 등이 포함될 수 있다.Examples of the liquid preparation for oral administration include suspensions, solutions, emulsions, and syrups. In addition to water and liquid paraffin, simple diluents commonly used, various excipients such as wetting agents, sweetening agents, have.

비경구 투여를 위한 제제에는 멸균된 수용액, 비수성 용제, 현탁제, 유제, 동결건조 제제, 좌제가 포함된다. 비수성 용제, 현탁제로는 프로필렌글리콜 (propylene glycol), 폴리에틸렌 글리콜, 올리브 오일과 같은 식물성 기름, 에틸올레이트와 같은 주사 가능한 에스테르 등이 사용될 수 있다. 좌제의 기제로는 위텝솔(witepsol), 마크로골, 트윈(tween) 61, 카카오지, 라우린지, 글리세로제라틴 등이 사용될 수 있다.
Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized formulations, suppositories. As the non-aqueous solvent and suspending agent, propylene glycol, polyethylene glycol, vegetable oils such as olive oil, injectable esters such as ethyl oleate and the like can be used. Examples of the suppository base include witepsol, macrogol, tween 61, cacao butter, laurin, glycerogelatin and the like.

또한, 본 발명은 곤달비 추출물, 이의 분획물 및 6종의 카페오일퀴닌산 유도체 또는 그의 약제학적으로 허용 가능한 염을 유효성분으로 포함하는 비만 관련 질환 예방 및 개선용 식품 조성물을 제공한다.
In addition, the present invention provides a food composition for preventing and improving obesity-related diseases, including gondal extract, fractions thereof, and six kinds of caffeoylquinine acid derivatives or pharmaceutically acceptable salts thereof as an active ingredient.

본 발명의 식품 조성물은 환제, 분말, 과립, 침제, 정제, 캡슐 또는 액제 등의 형태를 포함하며, 본 발명의 조성물을 첨가할 수 있는 식품으로는, 예를 들어, 각종 식품류, 예를 들어, 음료, 껌, 차, 비타민 복합제, 건강보조 식품류 등이 있다.
The food composition of the present invention includes the form of pills, powders, granules, acupuncture, tablets, capsules or liquids, and the like to which the composition of the present invention can be added, for example, various foods, for example, Drinks, gums, teas, vitamin complexes, and dietary supplements.

본 발명의 식품 조성물에서 포함할 수 있는 필수 성분으로서 상기 곤달비 추출물, 이의 분획물 및 6종의 카페오일퀴닌산 유도체을 포함하는 조성물 외 다른 성분에는 특별한 제한이 없으며 통상의 식품과 같이 여러 가지 생약 추출물, 식품 보조 첨가제 또는 천연 탄수화물 등을 추가 성분으로서 함유할 수 있다.As an essential ingredient that may be included in the food composition of the present invention, there are no particular limitations on other ingredients other than the composition including the gondalby extract, fractions thereof, and six kinds of caffeoylquininic acid derivatives. Supplementary additives or natural carbohydrates and the like may be included as additional ingredients.

또한, 상기 언급한 바와 같이 식품보조첨가제를 추가로 첨가할 수도 있는바 식품보조첨가제는 당업계에 통상적인 식품보조첨가제, 예를 들어 향미제, 풍미제, 착색제, 충진제, 안정화제 등을 포함한다.In addition, as mentioned above, the food supplement additive may further include food supplement additives, including food supplement additives conventional in the art, such as flavoring agents, flavoring agents, coloring agents, fillers, stabilizers, and the like. .

상기 천연 탄수화물의 예는 모노사카라이드, 예를 들어, 포도당, 과당 등; 디사카라이드, 예를 들어 말토스, 슈크로스 등; 및 폴리사카라이드, 예를 들어 덱스트린, 시클로덱스트린 등과 같은 통상적인 당, 및 자일리톨, 소르비톨, 에리트리톨 등의 당알콜이다. 상술한 것 이외의 향미제로서 천연 향미제(타우마틴, 스테비아 추출물(예를 들어 레바우디오시드 Ａ, 글리시르히진등) 및 합성 향미제(사카린, 아스파르탐 등)를 유리하게 사용할 수 있다.Examples of such natural carbohydrates include monosaccharides such as glucose, fructose, and the like; Disaccharides such as maltose, sucrose and the like; And conventional sugars such as polysaccharides such as dextrin, cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol. As flavoring agents other than those mentioned above, natural flavoring agents (tauumatin, stevia extract (e.g., rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.) can be advantageously used. .

상기 외에 본 발명의 식품 조성물은 여러 가지 영양제, 비타민, 광물(전해질), 합성 풍미제 및 천연 풍미제 등의 풍미제, 착색제 및 중진제(치즈, 초콜릿 등), 펙트산 및 그의 염, 알긴산 및 그의 염, 유기산, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알코올, 탄산 음료에 사용되는 탄산화제 등을 함유할 수 있다. 그밖에 천연 과일쥬스 및 과일 쥬스 음료 및 야채 음료의 제조를 위한 과육을 함유할 수 있다. 이러한 성분은 독립적으로 또는 조합하여 사용할 수 있다. In addition to the above, the food composition of the present invention can be used as a flavoring agent such as a variety of nutrients, vitamins, minerals (electrolytes), synthetic flavors and natural flavors, coloring agents and thickening agents (cheese, chocolate etc.), pectic acid and its salts, Salts thereof, organic acids, protective colloid thickeners, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, carbonating agents used in carbonated drinks, and the like. Others may contain pulp for the production of natural fruit juices and fruit juice drinks and vegetable drinks. These components can be used independently or in combination.

또한, 본 발명의 식품 조성물은 육류, 소세지, 빵, 쵸코렛, 캔디류, 스넥류, 과자류, 피자, 라면, 껌류, 아이스크림류, 스프, 음료수, 차, 기능수, 드링크제, 알콜 음료 및 비타민 복합제 중 어느 하나의 형태일 수 있다.
In addition, the food composition of the present invention is any one of meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, gum, ice cream, soup, beverage, tea, functional water, drink, alcoholic beverage and vitamin complex It may be in the form of.

또한, 본 발명은 곤달비 추출물, 이의 분획물 및 6종의 카페오일퀴닌산 유도체를 포함하는 조성물을 유효성분으로 포함하는 화장료 조성물에 관한 것이다. 본 발명에 따른 화장료 조성물에는 pH 조절제, 향료, 유화제, 방부제 등을 필요에 따라 부가하여 통상의 화장료 제조 방법으로 화장수, 젤, 수용성 파우더, 지용성 파우더, 수용성 리퀴드, 크림 또는 에센스 등으로 제형화될 수 있다.
In addition, the present invention relates to a cosmetic composition comprising a gondalbi extract, a fraction thereof and a composition comprising six kinds of caffeoylquinolinic acid derivatives as an active ingredient. The cosmetic composition according to the present invention may be formulated into a lotion, gel, water-soluble powder, fat-soluble powder, water-soluble liquid, cream or essence by adding a pH adjusting agent, flavoring agent, emulsifier, preservative, etc. as necessary in the usual cosmetic preparation method. have.

또한, 본 발명은 곤달비 추출물, 이의 분획물 및 6종의 카페오일퀴닌산 유도체를 포함하는 조성물을 유효성분으로 포함하는 의약외품 조성물에 관한 것이다. In addition, the present invention relates to a quasi-drug composition comprising a composition comprising gondalbi extract, fractions thereof, and six kinds of caffeoylquinolinic acid derivatives as active ingredients.

즉, 본 발명의 조성물은 비만 관련 질환의 예방 또는 개선을 목적으로 의약외품 조성물에 첨가될 수 있다. 본 발명의 곤달비 추출물, 이의 분획물 및 6종의 카페오일퀴닌산 유도체를 의약외품 첨가물로 사용할 경우, 상기 추출물, 분획물, 및 6종의 카페오일퀴닌산 유도체를 그대로 첨가하거나 다른 의약외품 또는 의약외품 성분과 함께 사용될 수 있고, 통상적인 방법에 따라 적절하게 사용될 수 있다. 유효 성분의 혼합양은 사용 목적(예방, 건강 또는 치료적 처치)에 따라 적합하게 결정될 수 있다. 바람직하게는, 상기 의약외품 조성물은 소독청결제, 샤워폼, 가그린, 물티슈, 세제비누, 핸드워시, 가습기 충진제, 마스크, 연고제, 코팅제 또는 필터충진제의 제조에 사용될 수 있다.
That is, the composition of the present invention may be added to the quasi-drug composition for the purpose of preventing or ameliorating obesity-related diseases. When the gondalbee extract of the present invention, its fractions and six kinds of caffeoylquininic acid derivatives are used as quasi-drug additives, the extracts, fractions and six kinds of caffeoylquinic acid derivatives can be added as they are or used together with other quasi-drugs or quasi-drug components. Can be suitably used according to conventional methods. The mixed amount of the active ingredient may be suitably determined depending on the purpose of use (prevention, health or therapeutic treatment). Preferably, the quasi-drug composition may be used for the preparation of antiseptic cleaners, shower foams, gagrins, wet tissues, detergent soaps, hand washes, humidifier fillers, masks, ointments, coating agents or filter fillers.

본 발명은 곤달비 추출물 또는 이의 분획물, 또는 이들로부터 유래된 화합물을 유효성분으로 하는 퍼옥시니트라이트 소거 활성을 갖는 조성물은 비만 관련 질환의 예방 또는 치료에 효과적이므로 비만 관련 질환의 개선, 예방, 및 치료를 위한 약학적 조성물, 식품 조성물, 화장료 조성물, 및 의약외품 조성물 등으로 사용될 수 있다.
The present invention is a composition having a peroxynitrite scavenging activity using a gondalby extract or a fraction thereof, or a compound derived therefrom as an active ingredient is effective in preventing or treating obesity-related diseases, thereby improving, preventing, and treating obesity-related diseases. For pharmaceutical compositions, food compositions, cosmetic compositions, and quasi-drug compositions and the like can be used.

도 1은 정량 분석을 위해 사용된 표준 화합물 1-7을 나타낸 것이다.
도 2은 7가지 표준 화합물, 곤달비 메탄올 추출물, 및 이들의 분획물(에테르 및 부탄올 분획물)의 HPLC 크로마토그램을 나타낸 것이다.
도 3은 L-페니실라민과 곤달비 메탄올 추출물의 페록시니트라이트 소거 효과를 비교하여 나타낸 것이다.
도 4는 5주째(W5)와 6주째(W6)에 곤달비 메탄올 추출물 및 그것의 부탄올 분획물이 고지방 식이를 섭취한 랫트 및 정상 식이를 섭취한 랫트의 체중에 미치는 효과를 나타낸 것이다.
도 5는 곤달비 메탄올 추출물 및 그것의 부탄올 분획물이 고지방 식이를 섭취한 랫트 및 정상 식이를 섭취한 랫트의 복강 지방 조직(후복강 및 부고환)에 미치는 효과를 나타낸 것이다. 1 shows standard compounds 1-7 used for quantitative analysis.
FIG. 2 shows HPLC chromatograms of seven standard compounds, gondal methanol extracts, and fractions thereof (ether and butanol fractions).
Figure 3 shows a comparison of the peroxynitrite scavenging effect of L- penicillamine and gondal methanol extract.
Figure 4 shows the effect of gondal methanol extract and its butanol fraction on the body weight of rats fed a high fat diet and rats fed a normal diet at 5th week (W5) and 6th week (W6).
FIG. 5 shows the effect of gondal methanol extract and its butanol fraction on the abdominal fat tissue (relaparotomy and epididymis) of rats fed a high fat diet and rats fed a normal diet.

이하，본 발명의 이해를 돕기 위하여 바람직한 실시예를 제시한다. 그러나 하기의 실시예는 본 발명을 더욱 쉽게 이해하기 위하여 제공되는 것일 뿐，실시예에 의하여 본 발명의 내용이 한정되는 것은 아니다.
Hereinafter, preferred embodiments of the present invention will be presented to assist in understanding the present invention. However, the following examples are merely provided to more easily understand the present invention, and the contents of the present invention are not limited by the examples.

실시예Example 1. 실험 방법 및 실험 재료 1. Experimental method and experimental material

식물plant

2009년 봄에 대한민국 강원도에서 L. stenocephala (국화과) 잎을 채취하였다.채취한 잎들은 실온에서 공기 건조하여 분말로 만들었다. 이 식물은 Dr. Won-Bae Kim (Highland Agriculture Research Institute, Rural Development Administration, Pyeongchang, Gangwon-do, Korea)에 의해 식별되었다.
In spring 2009, L. stenocephala (Asteraceae) leaves were collected from Gangwon-do, South Korea. The leaves were air dried at room temperature and powdered. This plant is It was identified by Won-Bae Kim (Highland Agriculture Research Institute, Rural Development Administration, Pyeongchang, Gangwon-do, Korea).

추출 및 분획Extraction and fractionation

80 ℃에서 7시간 동안 메탄올(10 L)을 이용하여 3번 공기 건조된 L. stenocephala (2 kg)의 잎의 추출물을 환류 추출하였다. 점성체(342 g)를 만들기 위해 감소된 압력 하에서 증류농축장치(rotary evaporator)를 사용하여 추출물을 농축하였다. 추출물(330 g)을 800 mL 물 내에 부유시키고 800 mL 에테르로 3번 분획하였다. 그리고 나서 남은 수층을 800 mL 부탄올로 3번 분획하였다. 이후에 에테르 및 분탄올 가용성 부분을 농축하고 freeze-dryer로 건조하여 에테르 및 부탄올 파우더 고체 분획물을 만들었다 (각각 108 g 및 119 g).
Extracts of leaves of L. stenocephala (2 kg), air-dried three times using methanol (10 L) at 80 ° C. for 7 hours, were refluxed. The extract was concentrated using a rotary evaporator under reduced pressure to make viscous body (342 g). The extract (330 g) was suspended in 800 mL water and partitioned three times with 800 mL ether. The remaining aqueous layer was then partitioned three times with 800 mL butanol. The ether and butanol soluble portions were then concentrated and dried with a freeze-dryer to give ether and butanol powder solid fractions (108 g and 119 g, respectively).

HPLCHPLC 분석을 위한 기구, 시약, 기초 화합물 Instruments, Reagents, and Basic Compounds for Analysis

Varian HPLC system (Walnut Creek, CA, USA)을 이용하여 L. stenocephala의 메탄올 추출물 및 그것의 분획물(에테르 및 부탄올) 내 포함되어 있는 카페오일퀴닌산을 분석하였다. 상기 Varian HPLC system은 Prostar 210 solvent delivery module, Prostar 325 UV-Vis detector 및 20 mL sample loop (Rheodyne, Rohnert Park, CA, USA)을 포함한다. Shiseido (Chuoku, Tokyo, Japan) Capcell Pak C18 column (5 mL, 250 mm x 4.6 mm I.D.) 위에서 분석 샘플의 화합물을 분리하였다. 분석을 위해 사용된 모든 용매는 J.T. Baker (Phillipsburg, NJ, USA)에서 수득한 HPLC grade였다. Lactuca indica L.로부터 분리된 7가지 표준 카페오일퀴닌산은 Prof. Kang Ro Lee (College of Pharmacy, SungKyunKwan University, Suwon, Korea)이 제공한 것을 사용하였다. 7가지 카페오일퀴닌산은 다음과 같다: 3,4-di-O-카페오일퀴닌산 (3,4-DQ), 3,5-Di-O-dicaffeoyl-epi-quinic acid (3,5-DeQ), 3,5-di-O-카페오일퀴닌산 (3,5-DQ), 4,5-di-O-카페오일퀴닌산 (4,5-DQ), 5-O-카페오일퀴닌산 (5-CQ), 3-O-카페오일퀴닌산 (3-CQ), 3-O-p-coumaroyl-카페오일퀴닌산 (3-pCQ). 7가지 표준 화합물의 구조는 도 1에 도시한 바와 같다. Varian HPLC system (Walnut Creek, CA, USA) was used to analyze the caffeoylquinic acid contained in the methanol extract of L. stenocephala and its fractions (ether and butanol). The Varian HPLC system includes a Prostar 210 solvent delivery module, a Prostar 325 UV-Vis detector and a 20 mL sample loop (Rheodyne, Rohnert Park, CA, USA). Shiseido (Chuoku, Tokyo, Japan) The compounds of the assay samples were isolated on Capcell Pak C18 column (5 mL, 250 mm × 4.6 mm ID). All solvents used for analysis were HPLC grade obtained from JT Baker (Phillipsburg, NJ, USA). Lactuca Seven standard caffeyl quinquinate isolated from indica L. The one provided by Kang Ro Lee (College of Pharmacy, SungKyun Kwan University, Suwon, Korea) was used. The seven caffeoylquinolinic acids are: 3,4-di- O -cafeoylquinic acid (3,4-DQ), 3,5-Di- O- dicaffeoyl- epi- quinic acid (3,5-DeQ ), 3,5-di- O -cafeoylquinolinic acid (3,5-DQ), 4,5-di- O -cafeoylquinic acid (4,5-DQ), 5- O -caoylquinic acid (5-CQ), 3- O - cafe five days quinic acid (3-CQ), 3- O - p -coumaroyl- cafe five days quinic acid (3-pCQ). The structures of the seven standard compounds are shown in FIG. 1.

카페오일퀴닌산Cafe Oil Quinine Acid 분석을 위한  For analysis HPLCHPLC 조건 Condition

HPLC 분석을 위해, 테스트 샘플 (메탄올 추출물, 에테르 및 부탄올 분획물)과 7가지 표준 화합물을 80% 메탄올에 용해시키고 0.50 mm 스프린지 필터(syringe filter)를 통해 필터링하였고 그 필터액을 (20mL) 분석기 안에 주입하였다. 유동상은 물 (용매 A) 및 메탄올 (용매 B) 안에 0.05% 인산 혼합물이였다. gradient system은 다음과 같다: 0-10 분, 60% A : 40% B; 10-20 분, 50% A : 50% B; 20-30 분, 40% A : 60% B; 30-35 분, 60% A : 40% B. 크로마토그래피는 1.00 mL min- 1유속율로 시행하였다. UV detector는 246 nm에 고정되었다. 추출물은 회귀방정식(regression equations)의 R2 값이 0.990이상이 된 후에 HPLC로 분석하였다.
For HPLC analysis, test samples (methanol extract, ether and butanol fractions) and seven standard compounds were dissolved in 80% methanol and filtered through a 0.50 mm sringe filter and the filter liquid was filtered into the (20 mL) analyzer. Injected. The fluidized bed was a 0.05% phosphoric acid mixture in water (solvent A) and methanol (solvent B). The gradient system is as follows: 0-10 minutes, 60% A: 40% B; 10-20 minutes, 50% A: 50% B; 20-30 minutes, 40% A: 60% B; 30-35 min, 60% A: 40% B. Chromatography was performed at 1.00 mL min - 1 flow rate. The UV detector was fixed at 246 nm. The extract was analyzed by HPLC after the R2 value of the regression equations was 0.990 or more.

퍼옥시니트라이트Peroxynitrite -소거 활성 분석-Clearing activity analysis

변경된 Kooy의 방법을 이용하여 퍼옥시니트라이트 (ONOO-) 소거 활성을 평가하였는데, 형광 로다민 123을 모니터링하는 것과 관련되어 있고, 이는 ONOO-의 존재 하에 비-형광성 DHR 123로부터 신속하게 생산되었다(Kooy et al., 1994). 즉, 로다민 버퍼 (pH 7.4)는 50 mM 소듐 포스페이트 디베이직, (sodium phosphate dibasic), 50 mM 소듐 포스페이트 모노베이직(sodium phosphate monobasic), 90 mM 소듐 클로라이드(sodium chloride), 5 mM 포타슘 클로라이드(potassium chloride), 및 100 μM DTPA로 구성되어 있다. 최종 DHR 123 농도는 5 μM이였다. 이 분석에서 버퍼는 사용 전에 준비하여 얼음 위에 두었다. 식물 추출물을 10% DMSO (f.c. 5 ㎍/mL)에서 용해시켰다. ONOO- (10 μM)와 함께 또는 제외된 상태로 처리한 후 5분 동안 배경 및 최종 형광 강도를 측정하고 0.3 N 소듐 하이드록사이드(sodium hydroxide) 안에 용해하였다. 산화된 DHR 123의 형광 강도는 각각 480 및 530 nm의 여기 및 발산 주파수에서 microplate fluorescence reader FL 500 (Bio-Tek Instruments Inc., Winooski, VT, USA)를 사용하여 측정되었다. 퍼옥시니트라이트-소거 활성값은 DHR 123 산화 탐지을 통해, 최종 형광 강도 마이너스 배경 형광 강도로 계산하였다.
The modified Kooy's method was used to assess peroxynitrite (ONOO − ) scavenging activity, which involves monitoring fluorescent rhodamine 123, which was rapidly produced from non-fluorescent DHR 123 in the presence of ONOO − ( Kooy et al., 1994). That is, rhodamine buffer (pH 7.4) is 50 mM sodium phosphate dibasic, (50 mM sodium phosphate dibasic), 50 mM sodium phosphate monobasic, 90 mM sodium chloride, 5 mM potassium chloride (potassium) chloride), and 100 μM DTPA. The final DHR 123 concentration was 5 μΜ. In this assay the buffer was prepared before use and placed on ice. Plant extracts were dissolved in 10% DMSO (fc 5 μg / mL). Background and final fluorescence intensities were measured and dissolved in 0.3 N sodium hydroxide for 5 minutes after treatment with or with ONOO − (10 μM). The fluorescence intensity of oxidized DHR 123 was measured using a microplate fluorescence reader FL 500 (Bio-Tek Instruments Inc., Winooski, VT, USA) at excitation and divergence frequencies of 480 and 530 nm, respectively. Peroxynitrite-erase activity values were calculated as the final fluorescence intensity minus background fluorescence intensity via DHR 123 oxidation detection.

실험 동물 및 처리Experimental animals and treatments

[(주) 효창사이언스(대구)]로부터 4주령의 140 ± 10 g의 Sprague Dawley(SD)계 흰랫트 수컷을 구입한 후 1주일 간 검역과 순화 사육을 거쳐 건강한 동물만을 실험에 이용하였다. 본 시험의 사육은 온도 22±3℃, 상대습도 50±10%, 조명시간 12시간(07:00～19:00)로 설정된 경성대학교 약학대학 실험동물 사육실에서 실시되었다. 사료는 실험동물용 고형사료(중앙실험동물, 서울)를 음수는 상수도를 자유 섭취시켰다. 실험 시간 전 24시간 동안 물만 주고 절식하였다. 이때 효소 활성의 일중 변동을 고려하여 실험동물을 일정시간(오전 10:00-12:00) 내에서 처치하였다. 이 실험은 경성 대학요 동물 보호 및 이용 위원회가 인증한다. 모든 절차는 국립보건연구원에서 공포한 '실험동물 관리와 이용에 관한 지침'에 따라 수행하였다. 곤달비 MeOH 추출물, Et2O 분획 및 BuOH 분획은 생리식염수로 용해한 4% tween 80을 사용하여 100, 200 mg/kg을 경구로 oral jonde를 이용해 실험동물에 2주간 투여하였다.
Four weeks old, 140 ± 10 g Sprague Dawley (SD) white rats were purchased from Hyochang Science Co., Ltd., and then healthy animals were used for the experiment after one week of quarantine and purified breeding. Breeding of this test was carried out in the laboratory animal breeding room of Kyungsung University Pharmacy set up with temperature 22 ± 3 ℃, relative humidity 50 ± 10%, lighting time 12 hours (07: 00 ~ 19: 00). Feed was freely ingested for drinking water, which was a solid feed for animals (Central Experimental Animal, Seoul). 24 hours before the experiment time only watering and fasting. At this time, the experimental animals were treated within a predetermined time (10: 00-12: 00 am) in consideration of the daily variation of enzyme activity. The experiment is certified by the Hard University Animal Care and Use Committee. All procedures were performed in accordance with the Guidelines for the Management and Use of Laboratory Animals, published by the National Institutes of Health. The gondal MeOH extract, the Et 2 O fraction and the BuOH fraction were administered orally with oral jonde at 100, 200 mg / kg for 2 weeks using 4% tween 80 dissolved in saline.

비만 및 고지혈증의 유발Induction of obesity and hyperlipidemia

고지방 식이 조성물은 표 1에 기재한 바와 같다. 6주 동안 고지방 식이를 섭취시켜 실험동물의 비만을 유발하였다. 전체 6주 중 마지막 2주간 시료를 경구 투여하여 항비만 효과를 관찰하였다.
The high fat dietary composition is as listed in Table 1. High fat diets were ingested for 6 weeks to induce obesity in experimental animals. The antiobesity effect was observed by oral administration of the sample for the last 2 weeks out of 6 weeks.

Figure 112010006567818-pat00002
Figure 112010006567818-pat00002

1) Cellulose : Sigma Co. LTD., USA 1) Cellulose: Sigma Co. LTD., USA

2) 다음을 포함하는 Rogers 와 Haper(1965) 유형에 기초한 미네랄 혼합물(g/kg diet): calcium phosphate dibasic 500.0, sodium chloride 74.0, potassium citrate monohydrate 220.0, potassium sulfate 52.0, magnesium oxide 24.0, magnesium carbonate 3.5, ferric citrate 6.0, zinc carbonate 1.6, cupuric carbonate 0.3, potassium iodate 0.01, chromium potassium sulfate 0.55, sucrose, finely powered make 1,000 2) Mineral mixture (g / kg diet) based on Rogers and Haper (1965) type, including: calcium phosphate dibasic 500.0, sodium chloride 74.0, potassium citrate monohydrate 220.0, potassium sulfate 52.0, magnesium oxide 24.0, magnesium carbonate 3.5, ferric citrate 6.0, zinc carbonate 1.6, cupuric carbonate 0.3, potassium iodate 0.01, chromium potassium sulfate 0.55, sucrose, finely powered make 1,000

3) Vitamin mixture(g/kg diet): thiamine HCl 0.6, biotin 0.02, riboflavin 0.6, cyanocobalamine 0.001, pyridoxine HCl 0.7, retinyl acetate 0.8, nicotinic acid 3.0, DL-tocopherol 3.8, Ca-pantothenate 1.6, 7-dehydrocholesterol 0.0025, folic acid 0.2, methionine 0.005, sucrose, finely powered make 1,000
 3) Vitamin mixture (g / kg diet): thiamine HCl 0.6, biotin 0.02, riboflavin 0.6, cyanocobalamine 0.001, pyridoxine HCl 0.7, retinyl acetate 0.8, nicotinic acid 3.0, DL-tocopherol 3.8, Ca-pantothenate 1.6, 7-dehydrocholesterol 0.0025 , folic acid 0.2, methionine 0.005, sucrose, finely powered make 1,000

혈청 조제Serum preparation

시료의 투입이 끝난 실험동물을 CO2로 가볍게 마취시켜 복부 대동맥으로부터 혈액을 채취하였고, 채취한 혈액은 30분간 방치한 후 3,000rpm에서 10분간 원심분리하여 혈청을 분리하여 지질 단백질, 하이드록실 라디칼 함량 및 슈퍼옥사이트 디스뮤테이즈 활성 측정에 사용하였다.
Blood was collected from the abdominal aorta by gently anesthetizing the experimental animals with CO 2 , and the collected blood was left for 30 minutes and centrifuged at 3,000 rpm for 10 minutes to separate serum, and the content of lipid protein and hydroxyl radicals. And superoxite dismutase activity measurement.

체중 및 복부 지방 조직의 무게 측정 Body weight and weight measurement of abdominal adipose tissue

체중 변화는 실험 개시일로부터 1주일마다 측정하였으며, 지방 조직의 중량은 시료 투입의 마지막 날에 복강 및 고환주위의 지방을 채취하여 산출하였다.
Body weight change was measured every week from the start of the experiment, the weight of the adipose tissue was calculated by taking the fat in the abdominal cavity and peri testicles on the last day of the sample input.

총 콜레스테롤 함량의 결정Determination of Total Cholesterol Content

Richmond(1976) 등의 효소법에 의하여 조제된 AM 202-K assay kit(Asan Pharm. Co., Korea)를 사용하여 혈청 내 총 콜레스테롤의 함량을 측정하였다. 빙냉상에서 용액 (cholesterol esterase 20.5 U/L, cholesterol oxidase 10.7 U/L, sodium hydroxide 1.81g/L, potassium phosphate monobasic 13.6 g/L, phenol 1.88 g/L 함유) 3㎖를 혈청 20㎕와 혼합하고 37℃에서 5 분간 부화시켰다. 총 콜레스테롤 함량을 결정하기 위해 시약 blank를 대조로 파장 550 nm에서 흡광도를 측정하였다. 표준 검량선에 준해 혈중 함량을 계산하였다.
Total cholesterol content in serum was measured using an AM 202-K assay kit (Asan Pharm. Co., Korea) prepared by an enzyme method such as Richmond (1976). In ice-cold phase, 3 ml of solution (containing 20.5 U / L cholesterol esterase, 10.7 U / L cholesterol oxidase, 1.81 g / L sodium hydroxide, 13.6 g / L potassium phosphate monobasic, 1.88 g / L phenol) are mixed with 20 μl of serum. Incubate at 37 ° C. for 5 minutes. To determine the total cholesterol content, the absorbance was measured at a wavelength of 550 nm against the reagent blank. Blood content was calculated according to a standard calibration curve.

HighHigh densitydensity lipoproteinlipoprotein -- cholesterolcholesterol ( ( HDLHDL -C) 함량의 결정-C) determination of content

Noma 등의 효소법(Noma et al., 1978)에 의하여 조제된 kit 시약(AM 203-K, Asan)를 사용하여 실험하였다. 혈청 20㎕에 침강시약(0.1% dextran, magnesium chloride 0.1M 함유) 0.2㎖를 가하고 잘 혼합한 후 실온에 방치하였다가 3000rpm에서 10 분간 원심분리하였다. 그 상징액을 0.1㎖ 취하여 효소시액 3.0㎖와 잘 혼합하여 37℃에서 5분간 부화하여 시약 blank를 대조로 파장 500㎚에서 흡광도를 측정하였다. 표준 검량선에 준해 그 함량을 ㎎/㎗로 표시하였다.
Experiments were carried out using kit reagents (AM 203-K, Asan) prepared by the enzyme method of Noma et al. (Noma et al., 1978). 0.2 ml of sedimentation reagent (containing 0.1% dextran and magnesium chloride 0.1M) was added to 20 µl of serum, and the mixture was mixed well and allowed to stand at room temperature. 0.1 ml of the supernatant was mixed well with 3.0 ml of enzyme solution and incubated at 37 ° C. for 5 minutes. The absorbance was measured at a wavelength of 500 nm using the reagent blank as a control. The content was expressed in mg / dl according to the standard calibration curve.

lowlow densitydensity lipoproteinlipoprotein ( ( LDLLDL )-) - cholesterolcholesterol 함량 측정 Content measurement

Low density lipoprotein-cholesterol(LDL-C) 함량은 Fridewald 등의 방법(Friedewald et al., 1972)에 따라 다음의 식에 의하여 산출하였다. LDL-C = [총콜레스테롤양 - (HDL-C + Triglyceride/5)]
Low density lipoprotein-cholesterol (LDL-C) content was calculated by the following equation according to Fridewald et al. (Friedewald et al., 1972). LDL-C = [Total Cholesterol Amount-(HDL-C + Triglyceride / 5)]

혈중 Blood TBARSTBARS 농도의 결정 Determination of concentration

Yagi et al. (1987) 등의 방법에 따라 혈청 TBARS 수치를 측정함으로써 혈청 지질 페록사이드 함량을 정량하였다. 혈청 20㎕에 1/12N H2SO4 4.0㎖를 가하여 혼합하고 인텅스텐산(phosphotungstic acid) 0.5㎖를 가하여 5분간 방치한 후 원심분리하여 침전물인 혈청단백질만 취해서 다시 1/12N H2SO4 2.0㎖와 10% 인텅스텐산(phosphotungstic acid) 0.3㎖를 가하여 원심분리하였다. 침전물만을 취하여 증류수 4.0㎖와 thiobarbituric acid-acetic acid (1:1)을 1.0㎖를 가하고 95℃에서 60분간 반응시켜 실온에서 냉각 후 n-BuOH을 5.0㎖를 첨가하여 3000rpm에서 15분간 원심분리한 후 생성된 홍색의 n-BuOH을 취해 spectrofluorometer를 사용하여(Ex : 515nm, Em : 553nm) 흡광도를 측정하였다.
Yagi et al. Serum lipid peroxide content was quantified by measuring serum TBARS levels according to the method of (1987) et al. 4.0 ml of 1 / 12N H 2 SO 4 was added to 20 µl of serum, mixed with 0.5 ml of phosphotungstic acid, and left for 5 minutes, followed by centrifugation, taking only the precipitated serum protein and again 1 / 12N H 2 SO 4. 2.0 ml and 10 ml of 10% phosphotungstic acid were added and centrifuged. Take the precipitate and add 4.0 ml of distilled water and 1.0 ml of thiobarbituric acid-acetic acid (1: 1), react at 60 ° C for 60 minutes, cool at room temperature, add 5.0 ml of n-BuOH, and centrifuge at 3000 rpm for 15 minutes. The resulting red n-BuOH was taken and absorbance was measured using a spectrofluorometer (Ex: 515 nm, Em: 553 nm).

혈중 Blood HydroxylHydroxyl radicalradical 농도 측정 Concentration measurement

Kobatake et al. (1987) 등의 방법에 따라 혈청 하이드록시 라디컬 수치를 측정하였다. 즉, 34.8㎕ 혈청에 0.54M NaCl, 0.1M potassium phosphate buffer(pH 7.4), 10mM NaN3, 7mM deoxyribose, 5mM ferrous ammonium sulfate 및 증류수를 포함하여 333.3㎕가 되도록 첨가하여 vortex에서 잘 혼합하여 37℃ 에서 15 분간 정치하였다. 이 혼합물 67ml를 취하고 여기에 8.1% sodium dodecyl sulfate 75ml, 20% acetic acid 67ml 및 증류수를 넣어 혼합하였다. 여기에 다시 1.2% thiobarbituric acid 222 ml를 가하여 water bath(100℃)에서 30 분간 가열한 후 실온에서 냉각한 다음 700×g에서 5분간 원심분리하여 얻은 상층액을 spectrophotometer을 사용하여 파장 532㎚에서 흡광도를 측정하여 표준 검량선에 의하여 hydroxyl radical(nmole/mg protein)의 함량을 정량하였다.
Kobatake et al. Serum hydroxy radical levels were measured according to the method of (1987) and the like. In other words, 34.8 μl serum was added to 333.3 μl including 0.54 M NaCl, 0.1 M potassium phosphate buffer (pH 7.4), 10 mM NaN 3 , 7 mM deoxyribose, 5 mM ferrous ammonium sulfate, and distilled water and mixed well in vortex at 37 ° C. It was left for 15 minutes. 67 ml of this mixture was taken and mixed with 75 ml of 8.1% sodium dodecyl sulfate, 67 ml of 20% acetic acid and distilled water. Then, 222 ml of 1.2% thiobarbituric acid was added thereto, followed by heating in a water bath (100 ° C.) for 30 minutes, cooling at room temperature, and centrifugation at 700 × g for 5 minutes, using a spectrophotometer to absorb absorbance at a wavelength of 532 nm. The amount of hydroxyl radical (nmole / mg protein) was determined by standard calibration curve.

혈중 Blood SuperoxideSuperoxide dismutasedismutase (( SODSOD ) 활성 측정) Active measurement

혈중 SOD 활성은 Oyanagui et al. (1984)에 기재된 방법을 사용하여 측정하였다. Mirsa와 Fridovich의 방법에 따라 정량하였다. 100 ml 혈청, 500 ml 증류수, 200 ml 시약 A (3 mM hydroxylamine/3 mM hypoxanthine), 200 ml 시약 B {7.5 mU/ml xanthine oxidase (XOD), 0.1 mM EDTA-2Na}를 포함하는 실험 튜브의 와류를 발생시킨 후 30분 동안 가만히 두었다. 2ml 시약 C (sulfanilic acid 300 mg/N-1-naphthyl-ethylenediamine 5.0 mg of 16.7% acetic acid)를 반응 혼합물에 첨가하고, 와류를 발생시킨 후 20분 동안 실온에 두었다. 혈청 중 SOD 활성 수치를 결정하기 위해, 550 nm에서 반응 혼합물의 UV-VIS 흡광도를 측정하고 표준 검량선에 준해 정량하였다.
Blood SOD activity is described by Oyanagui et al. It was measured using the method described in (1984). It was quantified according to the method of Mirsa and Fridovich. Vortex in laboratory tube containing 100 ml serum, 500 ml distilled water, 200 ml Reagent A (3 mM hydroxylamine / 3 mM hypoxanthine), 200 ml Reagent B {7.5 mU / ml xanthine oxidase (XOD), 0.1 mM EDTA-2Na} Allow to stand for 30 minutes after generating. 2 ml Reagent C (sulfanilic acid 300 mg / N-1-naphthyl-ethylenediamine 5.0 mg of 16.7% acetic acid) was added to the reaction mixture and allowed to vortex and left at room temperature for 20 minutes. To determine the level of SOD activity in serum, the UV-VIS absorbance of the reaction mixture at 550 nm was measured and quantified according to standard calibration curves.

실시예Example 2. 실험 결과  2. Experimental results

PeroxinitritePeroxinitrite -소거효과와 -Erasing effect and 카페오일퀴닌산의Of cafe oil quinic acid 성분분석 Component analysis

도 3에서 보듯이 곤달비 메탄올 추출물은 농도-의존적으로 퍼옥시니트라이트 형성을 매우 효과적으로 억제하였다. 그 억제 수준은 양성 대조군 L-페니실라민과 유사한 정도였다. 한국의 국화과 산채의 추출물로부터 퍼옥시니트라이트 소거효과 실험을 하였을 때 곤달비가 가장 현저한 활성을 보여 그 IC50 값이 0.87 ± 0.33 μg/ml이었다. 이 값은 양성 대조화합물인 페니실라민의 IC50 값 0.89 ± 0.22 μg/ml 와 비슷하게 나타나 곤달비 메탄올 추출물은 매우 강한 퍼옥시니트라이트 소거효과가 가지는 것으로 평가되었다.
As shown in FIG. 3, the gondal methanol extract effectively inhibited peroxynitrite formation in a concentration-dependent manner. The level of inhibition was similar to that of the positive control L-penicillamine. In the experiment of peroxynitrite scavenging effect from the extracts of Korean Asteraceae, gondal ratio showed the most remarkable activity, and the IC 50 value was 0.87 ± 0.33 μg / ml. This value was similar to the IC 50 value of 0.89 ± 0.22 μg / ml of penicillamine, a positive control compound, and it was evaluated that the gondal methanol extract had a very strong peroxynitrite scavenging effect.

이 메탄올 추출물을 HPLC 크로마토그램으로 분석하였을 때 모두 6종의 caffeoylquinic acid가 검출되었다. 곤달비가 3,5-di-O-caffeoylquinic acid (9.6 min)와 4,5-di-O-caffeoylquinic acid (17.1 min), 3,4-di-O-caffeoylquinic acid(2.7 min), 5-O-caffeoylquinic acid(4.5 min), 3-O-caffeoylquinic acid(8.9 min), 3-O-p-coumaroyl-caffeoylquinic acids(2.9 min)를 함유하고 있음이 처음으로 밝혀졌다. 괄호 안의 수치는 해당 화합물의 체류시간(retention time)이다. 그러나 표준 화합물로 사용한 3-O-p-coumaroylquinic acid는 함유하고 있지 않음이 관찰되었다. 식물재료 중 카페오일퀴닌산 총함량은 평균 11.60%로 나타났고 6종의 함유성분 중 3,5-di-O-caffeoylquinic acid가 메탄올 추출물 중 25.85%, 부탄올 분획물 중 약 41.32%를 차지하는 것으로 나타났다. 한편, 부탄올 분획에서는 6종의 caffeoylquinic acid가 94.52%를 차지하였다. 결과적으로 곤달비에는 caffeoylquinic acid류 화합물의 함량이 매우 높은 것으로 파악되었다. 표준 화합물과 곤달비 메탄올 추출물의 HPLC 크로마토그램은 도 2에 나타내었고 개별 화합물의 함량, 식물 중 총함량 및 추출물 중 총함량은 표 2에 나타내었다.
When the methanol extract was analyzed by HPLC chromatogram, all six kinds of caffeoylquinic acid were detected. Gondalabi was 3,5-di-O-caffeoylquinic acid (9.6 min), 4,5-di-O-caffeoylquinic acid (17.1 min), 3,4-di-O-caffeoylquinic acid (2.7 min), 5-O It was found for the first time that -caffeoylquinic acid (4.5 min), 3-O-caffeoylquinic acid (8.9 min) and 3-Op-coumaroyl-caffeoylquinic acids (2.9 min). The values in parentheses are the retention time of the compound. However, it was observed that it did not contain 3-O- p -coumaroylquinic acid used as a standard compound. The total content of caffeoylquinic acid in the plant material was 11.60% on average, and 3,5-di-O-caffeoylquinic acid among the six components contained 25.85% in methanol extract and 41.32% in butanol fraction. In the butanol fraction, six caffeoylquinic acids accounted for 94.52%. As a result, the content of caffeoylquinic acid compound was found to be very high in gondal ratio. HPLC chromatograms of the standard compound and gondal methanol extract are shown in FIG. 2 and the contents of the individual compounds, the total content in the plant and the total content in the extract are shown in Table 2.

Figure 112010006567818-pat00003
Figure 112010006567818-pat00003

a 값들은 3번 중복 실험의 값을 평균±S.D.하여 나타낸 것임,, bND : 탐지된 바 없음
will have a value indicated by mean ± SD values of three duplicate experiments ,, b ND: Not Detected Bar

비만 obesity 랫트의Rat 체중, 복부 지방조직의 변화 Changes in body weight and abdominal adipose tissue

이 추출물의 항비만효과를 실험하기 위하여 표 1과 같이 고지방 식이를 랫트에 6주간 경구투여하여 비만을 유도하였다. 마지막 2주간 곤달비 메탄올 추출물, 에테르 분획 및 부탄올 분획을 경구투여하여 비만에 대한 억제효과를 실험하였다. 조사항목으로 체중변화(도 4), 지방조직의 무게변화(도 5)를 측정하였다.To test the anti-obesity effect of this extract As shown in Fig. 1, a high fat diet was orally administered to rats for 6 weeks to induce obesity. Gondalbi methanol extract, ether fraction and butanol fraction were orally administered for the last 2 weeks to test the inhibitory effect on obesity. As a survey item, weight change (FIG. 4) and a change in weight of adipose tissue (FIG. 5) were measured.

메탄올 추출물, 에테르 분획물 및 부탄올 분획물 모두 활성이 있으나 부탄올 분획물이 가장 유의한 비만 억제 효과를 나타냈다. 부탄올 분획물은 체중 및 복부 지방 조직 무게를 정상군 수준으로 유의하게 감소시켰다. 이상과 같은 실험결과로부터 곤달비 메탄올 추출물은 항비만효과를 가지는 매우 효과적인 추출물로 개발할 수 있을 것임을 예측할 수 있다. 또한 부탄올 분획물에 가장 많은 함량의 caffeoylquinic acid이 함유(94.52%)되어 있으므로 이들 화합물이 비만억제에 주로 기여한 것으로 판단된다. Methanol extract, ether fraction and butanol fraction were all active, but butanol fraction showed the most significant obesity inhibitory effect. Butanol fraction significantly reduced body weight and abdominal adipose tissue weight to normal group level. From the above experimental results, it can be predicted that the gondal methanol extract can be developed as a very effective extract having an anti-obesity effect. Butanol fractions contain the highest amount of caffeoylquinic acid (94.52%).

복부 지방조직의 무게를 조사하여 도 5에 나타내었다. 후복강 지방조직과 부고환 지방조직의 무게 변화를 조사한 결과 메탄올 추출물, 에테르 분획물 및 부탄올 분획물이 모두 유의성 있게 중량을 감소시켰다. 특히, 가장 현저한 효과를 나타내었던 부탄올 분획 200mg/kg 투여군에서는 후복강 지방조직과 부고환 지방조직의 무게가 각각 53.4%와 45.8% 감소시키는 효과를 나타내었다.
Check the weight of abdominal adipose tissue 5 is shown. The weight changes of the celiac adipose tissue and epididymal adipose tissue were significantly reduced in the methanol, ether and butanol fractions. In particular, the 200 mg / kg butanol fraction showed the most remarkable effect in reducing the weight of posterior cavity and epididymal adipose tissue by 53.4% and 45.8%, respectively.

비만 랫트Obese Rat 에서in 동맥경화 지수의 변화 Change in Atherosclerosis Index

흰랫트의 혈청 총 콜레스테롤, HDL-콜레스테롤, LDL-콜레스테롤을 조사한 결과를 표 3에 나타내었다. 곤달비 메탄올 추출물, 에테르 추출물 및 부탄올 추출물이 모두 유의성있게 총 콜레스테롤과 LDL-콜레스테롤은 감소시켰으나 혈청 HDL-콜레스테롤에는 큰 변화를 주지못했다(표 3). Serum total cholesterol, HDL-cholesterol, and LDL-cholesterol of the rats were examined. Table 3 shows the results. Gondalbi methanol extract, ether extract and butanol extract all significantly reduced total cholesterol and LDL-cholesterol but did not significantly change serum HDL-cholesterol (Table 3).

동맥경화 위험지수에서는 정상 랫트가 0.42 ± 0.09의 수치를 나타내던 것이 대조군에서는 1.81 ± 0.13의 수치를 보여 크게 증가하였다. 투여군들은 모두 동맥경화 위험을 완화시켜 동맥경화에 유익한 것으로 나타났다. 특히 가장 큰 효과를 나타낸 부탄올 분획물 투여군은 1.22 ± 0.11의 동맥경화 위험지수를 나타냈다(표 3).
In the atherosclerosis risk index, the normal rats showed 0.42 ± 0.09 and the control group increased 1.81 ± 0.13. All of the administered groups were shown to be beneficial for atherosclerosis by reducing the risk of atherosclerosis. In particular, the butanol fraction administration group exhibited the greatest atherosclerotic risk index of 1.22 ± 0.11 (Table 3).

Figure 112010006567818-pat00004
Figure 112010006567818-pat00004

분석 절차는 실험 방법에 기술되어 있음. 값은 6번 실험한 값을 평균± S.D.한 것임. 동일한 문자에 따른 값은 유의성있는 차이가 없음(p<0.05).The analytical procedure is described in the experimental method. Values are the average ± S.D. of the six experiments. Values according to the same letter do not differ significantly (p <0.05).

동맥경화 지수(AI;Atheroscrelosis Index) =(전체 콜레스테롤 - HDL cholesterol) / HDL cholesterol　
Atherosclerosis Index (AI) = (total cholesterol-HDL cholesterol) / HDL cholesterol

비만 랫트Obese Rat 에서in TBARSTBARS 에의 효과Effect on

TBARS, 하이드록시 라디컬 및 SOD 활성의 수치는 정상군과 비교하여 대조군에서 매우 증가하였다(표 4). 이는 활성산소종(reactive oxygen species ;ROS), 지질 퍼옥시데이션(lipid peroxidation) 및 산화스트레스(oxidative stress)의 증가를 암시한다. 메탄올 추출물과 모든 분획물은 증가된 TBARS, 하이드록시 라디컬 수치 및 증가된 SOD 활성 수치를 억제하였다. 특히, 이러한 억제 효과는 부탄올 200mg/kg의 투여군에서 가장 현저하였다.
Levels of TBARS, hydroxy radicals and SOD activity were significantly increased in the control group compared to the normal group (Table 4). This suggests an increase in reactive oxygen species (ROS), lipid peroxidation and oxidative stress. Methanol extract and all fractions inhibited increased TBARS, hydroxy radical levels and increased SOD activity levels. In particular, this inhibitory effect was most remarkable in the butaneol 200 mg / kg administration group.

Figure 112010006567818-pat00005
Figure 112010006567818-pat00005

분석 절차는 실험 방법에 기술되어 있음. 값은 6번 실험한 값을 평균± S.D.한 것임. 동일한 문자에 따른 값은 유의성있는 차이가 없음(p<0.05).The analytical procedure is described in the experimental method. Values are the average ± S.D. of the six experiments. Values according to the same letter do not differ significantly (p <0.05).

SOD 1 Unit : adrenochrome 형성율을 50%로 억제하는 효소의 양으로 정의됨
SOD 1 Unit: defined as the amount of enzyme that inhibits adrenochrome formation rate by 50%

Claims (22)

삭제delete 삭제delete 삭제delete 삭제delete 삭제delete 삭제delete 삭제delete 삭제delete 삭제delete 삭제delete 삭제delete 삭제delete 삭제delete 삭제delete 삭제delete 곤달비를 메탄올로 추출하여 곤달비 추출물을 얻는 제1단계; 및
상기 곤달비 추출물로부터 3,5-di-O-dicaffeoyl-epi-quinic acid(3,5-DeQ), 4,5-di-O-caffeoylquinic acid(4,5-DQ), 5-O-caffeoylquinic acid(5-CQ) 및 3-O-caffeoylquinic acid(3-CQ)로 이루어진 군으로부터 선택되는 1 종 이상의 화합물을 분리하는 제2단계를 포함하는, 곤달비로부터 3,5-di-O-dicaffeoyl-epi-quinic acid(3,5-DeQ), 4,5-di-O-caffeoylquinic acid(4,5-DQ), 5-O-caffeoylquinic acid(5-CQ) 및 3-O-caffeoylquinic acid(3-CQ)로 이루어진 군으로부터 선택되는 1 종 이상의 화합물 분리방법.
A first step of obtaining gondal extract by extracting gondal with methanol; And
From the extract gondalbi 3,5-di- O -dicaffeoyl- epi -quinic acid (3,5-DeQ), 4,5-di-O-caffeoylquinic acid (4,5-DQ), 5- O -caffeoylquinic acid 3,5-di- O- dicaffeoyl- epi from gondalby, comprising a second step of separating one or more compounds selected from the group consisting of (5-CQ) and 3- O- caffeoylquinic acid (3-CQ) -quinic acid (3,5-DeQ), 4,5-di-O-caffeoylquinic acid (4,5-DQ), 5- O -caffeoylquinic acid (5-CQ), and 3- O -caffeoylquinic acid (3- CQ) at least one compound separation method selected from the group consisting of.
곤달비를 메탄올로 추출하여 곤달비 추출물을 얻는 제1단계;
상기 곤달비 추출물을 부탄올로 분획하여 곤달비의 분획물을 얻는 제2단계; 및
상기 분획물로부터 3,5-di-O-dicaffeoyl-epi-quinic acid(3,5-DeQ), 4,5-di-O-caffeoylquinic acid(4,5-DQ), 5-O-caffeoylquinic acid(5-CQ) 및 3-O-caffeoylquinic acid(3-CQ)로 이루어진 군으로부터 선택되는 1 종 이상의 화합물을 분리하는 제3단계를 포함하는, 곤달비로부터 3,5-di-O-dicaffeoyl-epi-quinic acid(3,5-DeQ), 4,5-di-O-caffeoylquinic acid(4,5-DQ), 5-O-caffeoylquinic acid(5-CQ) 및 3-O-caffeoylquinic acid(3-CQ)로 이루어진 군으로부터 선택되는 1 종 이상의 화합물 분리방법.A first step of obtaining gondal extract by extracting gondal with methanol;
A second step of dividing the gondalby extract with butanol to obtain a fraction of gondalby; And
From the fraction 3,5-di- O -dicaffeoyl- epi -quinic acid (3,5-DeQ), 4,5-di-O-caffeoylquinic acid (4,5-DQ), 5- O -caffeoylquinic acid ( 5-CQ) and 3- O -caffeoylquinic acid (3-CQ ), 3,5-di- O from gondalbi comprising a third step of separating the at least one compound selected from the group consisting of -dicaffeoyl- epi - quinic acid (3,5-DeQ), 4,5-di-O-caffeoylquinic acid (4,5-DQ), 5- O -caffeoylquinic acid (5-CQ) and 3- O -caffeoylquinic acid (3-CQ At least one compound selected from the group consisting of: 곤달비(Ligularia stenocephala) 메탄올 추출물을 유효성분으로 함유하는 비만의 치료용 약제학적 조성물.
A pharmaceutical composition for the treatment of obesity, which contains methanol extract of Ligularia stenocephala as an active ingredient.
곤달비(Ligularia stenocephala) 메탄올 추출물을 유효성분으로 함유하는 비만의 예방 또는 개선용 식품 조성물.
Gonalbi (Ligularia stenocephala) Food composition for the prevention or improvement of obesity containing methanol extract as an active ingredient.
곤달비(Ligularia stenocephala) 메탄올 추출물의 부탄올 분획물 또는 에테르 분획물을 유효성분으로 함유하는 비만 치료용 약제학적 조성물.
A pharmaceutical composition for treating obesity, comprising butanol fraction or ether fraction of methanol extract of Ligularia stenocephala as an active ingredient.
곤달비(Ligularia stenocephala) 메탄올 추출물의 부탄올 분획물 또는 에테르 분획물을 유효성분으로 함유하는 비만의 예방 또는 개선용 식품 조성물.
Food composition for the prevention or improvement of obesity containing butanol fraction or ether fraction of methanol extract of Ligularia stenocephala as an active ingredient.
곤달비를 메탄올로 추출하여 곤달비 추출물을 얻는 제1단계;
상기 곤달비 추출물을 에테르로 분획하여 곤달비의 분획물을 얻는 제2단계; 및
상기 분획물로부터 5-O-caffeoylquinic acid(5-CQ)를 분리하는 제3단계를 포함하는, 곤달비로부터 5-O-caffeoylquinic acid(5-CQ)의 분리방법.





A first step of obtaining gondal extract by extracting gondal with methanol;
A second step of fractionating the gondalby extract with ether to obtain a fraction of gondalby; And
Method of separating the fractions from 5- O -caffeoylquinic acid (5-CQ ) 5- O -caffeoylquinic acid (5-CQ), from gondalbi comprising a third step of separating.





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WO2020210161A1 (en) * 2019-04-06 2020-10-15 Cargill, Incorporated Methods for making botanical extract composition
WO2021182661A1 (en) * 2020-03-13 2021-09-16 주식회사 네이처센스 농업회사법인 Composition for improving antibacterial, anti-inflammatory, antiviral, and immune functions, comprising extract of ligularia stenocephala as active ingredient
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WO2020210161A1 (en) * 2019-04-06 2020-10-15 Cargill, Incorporated Methods for making botanical extract composition
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KR102402318B1 (en) 2020-03-13 2022-05-26 주식회사 네이처센스 Antimicrobial, anti-inflammatory, antiviral and immunologically enhancing composition comprising extract of ligularia stenocephala

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